APITesting_report.html

------------------------------Captured stdout call------------------------------
"Already closed!"

------------------------------Captured stdout call------------------------------
<h1>Server Error (500)</h1>

------------------------------Captured stdout call------------------------------
{"Result":[{"TrainingID":"1","Result":[{"Segmenter":"None","Word_Vectorizer":"Count_Vectorizer","Classification_Algo":"Decision_Tree","performanceReport":{"accuracy":0.9053254437869822,"recall":0.8273447322102087,"precision":0.85628078817734,"classificationReport":{"ANIMAL":{"precision":0.7816,"recall":0.701,"f1-score":0.7391,"support":97},"HUMAN":{"precision":0.931,"recall":0.9537,"f1-score":0.9422,"support":410},"accuracy":0.9053254437869822,"macro avg":{"precision":0.8563,"recall":0.8273,"f1-score":0.8406,"support":507},"weighted avg":{"precision":0.9024,"recall":0.9053,"f1-score":0.9033,"support":507}}},"save_status":"closed","exposed":"True","model_id":"7b78839470e28e20fabe0a77cf4bac34","model_name":"Test"}]}]}

------------------------------Captured stdout call------------------------------
{"Exposed":[{"project_id":"PID100085","models":[{"training_id":"1","alg_names":[{"AlgName":{"Segmenter":"None","Word_Vectorizer":"Count_Vectorizer","Classification_Algo":"Decision_Tree"}}]},{"training_id":"2","alg_names":[{"AlgName":{"Segmenter":"None","Word_Vectorizer":"Count_Vectorizer","Classification_Algo":"KNeighbors"}}]}]},{"project_id":"PID100086","models":[]},{"project_id":"PID100087","models":[{"training_id":"1","alg_names":[{"AlgName":{"Segmenter":"None","Word_Vectorizer":"Count_Vectorizer","Classification_Algo":"Gradient_Boosting"}}]}]},{"project_id":"PID100088","models":[{"training_id":"100739","alg_names":[]}]},{"project_id":"PID100089","models":[{"training_id":"100740","alg_names":[]}]},{"project_id":"PID100091","models":[{"training_id":"100807","alg_names":[]}]},{"project_id":"PID100092","models":[{"training_id":"fa320b305def5d8e77237b0b15c786bb","alg_names":[]}]},{"project_id":"PID100107","models":[{"training_id":"1","alg_names":[]},{"training_id":"2","alg_names":[]}]},{"project_id":"PID100108","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100109","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100110","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100111","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100112","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100113","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100114","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100115","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100116","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100117","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100132","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100133","models":[]},{"project_id":"PID100134","models":[]},{"project_id":"PID100135","models":[]},{"project_id":"PID100136","models":[]},{"project_id":"PID100137","models":[{"training_id":"1","alg_names":[{"AlgName":{"Segmenter":"None","Word_Vectorizer":"Count_Vectorizer","Classification_Algo":"Decision_Tree"}}]}]},{"project_id":"PID100138","models":[{"training_id":"386f52d3d9fecdd99cbbe1eadba307fa","alg_names":[]}]},{"project_id":"PID100140","models":[{"training_id":"1","alg_names":[]}]},{"project_id":"PID100141","models":[]},{"project_id":"PID100142","models":[]},{"project_id":"PID100143","models":[]},{"project_id":"PID100144","models":[]},{"project_id":"PID100145","models":[]},{"project_id":"PID100146","models":[]},{"project_id":"PID100147","models":[]},{"project_id":"PID100148","models":[]},{"project_id":"PID100149","models":[]},{"project_id":"PID100150","models":[]}]} 200

------------------------------Captured stdout call------------------------------
{"Key":"d0f4ac5d0ddf6f4a7bcedce7904f054f"}

------------------------------Captured stdout call------------------------------
{"Result":{"Segmenter":"None","Word_Vectorizer":"Count_Vectorizer","Classification_Algo":"Decision_Tree","performanceReport":"{'accuracy': 0.9601328903654485, 'recall': 0.9160879888893867, 'precision': 0.9489881752347066, 'classificationReport': {'ANIMAL': {'precision': 0.9322, 'recall': 0.8462, 'f1-score': 0.8871, 'support': 390}, 'HUMAN': {'precision': 0.9658, 'recall': 0.986, 'f1-score': 0.9758, 'support': 1717}, 'accuracy': 0.9601328903654485, 'macro avg': {'precision': 0.949, 'recall': 0.9161, 'f1-score': 0.9314, 'support': 2107}, 'weighted avg': {'precision': 0.9596, 'recall': 0.9601, 'f1-score': 0.9594, 'support': 2107}}}","data":[{"cleaned":"annexin 1 downregulation associated clinical outcome chinese patients hilar cholangiocarcinoma aims annexin a1 anxa1 calcium phospholipid binding protein implicated regulating inflammatory responses cell proliferation apoptosis evidence importance carcinogenesis increased rapidly however status anxa1 hilar cholangiocarcinoma remains unclear detected anxa1 expression determined clinical significance chinese patients hilar cholangiocarcinoma methods tissue microarray blocks containing tumor specimens obtained 61 patients constructed expression anxa1 specimens analyzed using immunohistochemical studies results anxa1 expression observed 27 cases 44 3 loss anxa1 expression significantly associated lymph node metastases histopathologic grade anxa1 expression significant inverse correlation recurrence poor survival univariate analyses multivariate analyses revealed loss anxa1 expression independent predictor future recurrence overall survival patients cholangiocarcinoma conclusions decreased expression anxa1 common event human hilar cholangiocarcinoma significantly correlated poor outcome patients cholangiocarcinoma suggesting potential role anxa1 cancer development progression stn","probabilities":0.9467213,"Title":"Annexin-1 Downregulation Is Associated With Clinical Outcome In Chinese Patients With Hilar Cholangiocarcinoma","Abstract":"Aims: Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein and has been implicated in regulating inflammatory responses, cell proliferation and apoptosis. The evidence of its importance in carcinogenesis increased rapidly. However, the status of ANXA1 in hilar cholangiocarcinoma remains unclear. Here, we detected ANXA1 expression and determined its clinical significance in Chinese patients with hilar cholangiocarcinoma. \r\n\r\n Methods: Tissue microarray blocks containing tumor specimens obtained from 61 patients were constructed. Expression of ANXA1 in these specimens was analyzed using immunohistochemical studies. \r\n\r\n Results: ANXA1 expression was observed in 27 cases (44.3%). Loss of ANXA1 expression was significantly associated with lymph node metastases and histopathologic grade. ANXA1 expression has a significant inverse correlation with recurrence and poor survival in univariate analyses.Multivariate analyses revealed that loss of ANXA1 expression was an independent predictor for future recurrence and overall survival in patients with cholangiocarcinoma. \r\n\r\n Conclusions: Decreased expression of ANXA1 is a common event in human hilar cholangiocarcinoma and is significantly correlated with the poor outcome of patients with cholangiocarcinoma, suggesting a potential role of ANXA1 in cancer development and progression.","Source":"STN","category":"ANIMAL","training_data":"Annexin-1 Downregulation Is Associated With Clinical Outcome In Chinese Patients With Hilar Cholangiocarcinoma Aims: Annexin A1 (ANXA1) is a calcium- and phospholipid-binding protein and has been implicated in regulating inflammatory responses, cell proliferation and apoptosis. The evidence of its importance in carcinogenesis increased rapidly. However, the status of ANXA1 in hilar cholangiocarcinoma remains unclear. Here, we detected ANXA1 expression and determined its clinical significance in Chinese patients with hilar cholangiocarcinoma. \r\n\r\n Methods: Tissue microarray blocks containing tumor specimens obtained from 61 patients were constructed. Expression of ANXA1 in these specimens was analyzed using immunohistochemical studies. \r\n\r\n Results: ANXA1 expression was observed in 27 cases (44.3%). Loss of ANXA1 expression was significantly associated with lymph node metastases and histopathologic grade. ANXA1 expression has a significant inverse correlation with recurrence and poor survival in univariate analyses.Multivariate analyses revealed that loss of ANXA1 expression was an independent predictor for future recurrence and overall survival in patients with cholangiocarcinoma. \r\n\r\n Conclusions: Decreased expression of ANXA1 is a common event in human hilar cholangiocarcinoma and is significantly correlated with the poor outcome of patients with cholangiocarcinoma, suggesting a potential role of ANXA1 in cancer development and progression. STN","prediction_labels":"ANIMAL"},{"cleaned":"ca 19 9 pancreatic cancer retrospective evaluation patients suspicion pancreatic cancer ca 19 9 serum levels prospectively determined 573 patients admitted hospital suspicion pancreatic cancer final diagnosis 77 patients malignancy 389 patients pancreatic cancer 37 neuroendocrine pancreatic cancer 28 cholangiocarcinomas 4 gallbladder cancer 27 ampullary carcinomas 11 periampullary carcinomas ca 19 9 determined using commercial assay roche diagnostics 37 u ml considered upper limit normality abnormal ca 19 9 serum levels found 27 81 5 85 7 59 3 63 6 18 9 patients benign diseases pancreatic cancer cholangiocarcinomas ampullary periampullary neuroendocrine tumors significantly higher concentrations ca 19 9 found patients without malignancy neuroendocrine tumors ca 19 9 serum levels higher pancreatic cancer cholangiocarcinoma malignancies p 0 0001 ca 19 9 serum levels also correlated tumor stage treatment significantly lower concentrations resectable tumors tumor location highest located body lowest tail uncinate site metastases highest liver metastases trend higher ca 19 9 serum concentrations found patients jaundice statistical significance early stages using 50 100 u ml patients jaundice ca 19 9 useful aid diagnosis pancreatic cancer sensitivity 77 9 specificity 95 9 well tumor resectability pancreatic cancer different cutoffs according tumor location bilirubin serum levels specificities ranging 90 100 ca 19 9 tumor marker choice pancreatic adenocarcinomas clear relationship tumor location stage resectability pubmed","probabilities":0.9799733,"Title":"CA 19-9 in pancreatic cancer: retrospective evaluation of patients with suspicion of pancreatic cancer","Abstract":"CA 19.9 serum levels were prospectively determined in 573 patients admitted to hospital for suspicion of pancreatic cancer. The final diagnosis was 77 patients with no malignancy, 389 patients with pancreatic cancer, 37 neuroendocrine pancreatic cancer, 28 cholangiocarcinomas, 4 gallbladder cancer, 27 ampullary carcinomas, and 11 periampullary carcinomas. CA 19.9 was determined using a commercial assay from Roche Diagnostics, and 37 U/ml was considered as the upper limit of normality. Abnormal CA 19.9 serum levels were found in 27%, 81.5%, 85.7%, 59.3%, 63.6%, and 18.9% of patients with benign diseases, pancreatic cancer, cholangiocarcinomas, and ampullary, periampullary, or neuroendocrine tumors. Significantly higher concentrations of CA 19.9 were found in patients with than in those without malignancy or with neuroendocrine tumors. CA 19.9 serum levels were higher in pancreatic cancer or cholangiocarcinoma than in other malignancies (p < 0.0001). CA 19.9 serum levels were also correlated with tumor stage, treatment (significantly lower concentrations in resectable tumors), and tumor location (the highest in those located in the body, the lowest in those in the tail or uncinate) and site of metastases (highest in liver metastases). A trend to higher CA 19.9 serum concentrations was found in patients with jaundice, but only with statistical significance in the early stages. Using 50 or 100 U/ml in patients with jaundice, CA 19.9 was useful as an aid in the diagnosis of pancreatic cancer (sensitivity 77.9%, specificity 95.9%) as well as tumor resectability in pancreatic cancer with different cutoffs according to tumor location and bilirubin serum levels with specificities ranging from 90% to 100%. CA 19.9 is the tumor marker of choice in pancreatic adenocarcinomas, with a clear relationship with tumor location, stage, and resectability.","Source":"PubMed","category":"HUMAN","training_data":"CA 19-9 in pancreatic cancer: retrospective evaluation of patients with suspicion of pancreatic cancer CA 19.9 serum levels were prospectively determined in 573 patients admitted to hospital for suspicion of pancreatic cancer. The final diagnosis was 77 patients with no malignancy, 389 patients with pancreatic cancer, 37 neuroendocrine pancreatic cancer, 28 cholangiocarcinomas, 4 gallbladder cancer, 27 ampullary carcinomas, and 11 periampullary carcinomas. CA 19.9 was determined using a commercial assay from Roche Diagnostics, and 37 U/ml was considered as the upper limit of normality. Abnormal CA 19.9 serum levels were found in 27%, 81.5%, 85.7%, 59.3%, 63.6%, and 18.9% of patients with benign diseases, pancreatic cancer, cholangiocarcinomas, and ampullary, periampullary, or neuroendocrine tumors. Significantly higher concentrations of CA 19.9 were found in patients with than in those without malignancy or with neuroendocrine tumors. CA 19.9 serum levels were higher in pancreatic cancer or cholangiocarcinoma than in other malignancies (p < 0.0001). CA 19.9 serum levels were also correlated with tumor stage, treatment (significantly lower concentrations in resectable tumors), and tumor location (the highest in those located in the body, the lowest in those in the tail or uncinate) and site of metastases (highest in liver metastases). A trend to higher CA 19.9 serum concentrations was found in patients with jaundice, but only with statistical significance in the early stages. Using 50 or 100 U/ml in patients with jaundice, CA 19.9 was useful as an aid in the diagnosis of pancreatic cancer (sensitivity 77.9%, specificity 95.9%) as well as tumor resectability in pancreatic cancer with different cutoffs according to tumor location and bilirubin serum levels with specificities ranging from 90% to 100%. CA 19.9 is the tumor marker of choice in pancreatic adenocarcinomas, with a clear relationship with tumor location, stage, and resectability. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association small intestinal bacterial overgrowth toll like receptor 4 patients pancreatic carcinoma cholangiocarcinoma background aims multiple factors linked pathogenesis pancreatic cancer cholangiocarcinoma studies investigated role small intestinal bacterial overgrowth sibo toll like receptor 4 tlr 4 signaling diseases study aimed examine relationship prevalence sibo tlr 4 expression patients pancreatic carcinoma cholangiocarcinoma materials methods total 90 human subjects suffering pancreatic carcinoma n 30 cholangiocarcinoma n 30 healthy controls n 30 enrolled study glucose hydrogen breath test ghbt used evaluate sibo tlr4 protein expression measured immunohistochemistry ihc results positive rate sibo 63 3 pancreatic cancer group 46 7 patients cholangiocarcinoma significantly greater 13 3 healthy control group p 0 05 ihc analysis revealed tlr 4 protein expression sibo positive pancreatic carcinoma patients significantly higher sibo negative patients p 0 05 result cholangiocarcinoma subjects addition correlation analysis identified positive relationship prevalence sibo tlr 4 protein expression pancreatic carcinoma r 0 489 result cholangiocarcinoma subjects conclusion findings indicate high prevalence sibo pancreatic carcinoma cholangiocarcinoma sibo displays positive correlation tlr 4 expression suggesting sibo risk factor pathogenesis pancreatic carcinoma cholangiocarcinoma tlr4 signaling may involved pubmed","probabilities":0.8684211,"Title":"Association between small intestinal bacterial overgrowth and toll-like receptor 4 in patients with pancreatic carcinoma and cholangiocarcinoma","Abstract":"BACKGROUND/AIMS: Multiple factors have been linked to pathogenesis of pancreatic cancer and cholangiocarcinoma. Until now, few studies have investigated the role of small intestinal bacterial overgrowth (SIBO) and toll-like receptor 4 (TLR-4) signaling in these diseases. This study aimed to examine the relationship between the prevalence of SIBO and the TLR-4 expression in patients with pancreatic carcinoma and cholangiocarcinoma. MATERIALS AND METHODS: A total of 90 human subjects suffering from pancreatic carcinoma (n=30), cholangiocarcinoma (n=30), and healthy controls (n=30) were enrolled in the study. A glucose hydrogen breath test (GHBT) was used to evaluate SIBO. The TLR4 protein expression was measured by immunohistochemistry (IHC). RESULTS: The positive rate of SIBO was 63.3% in the pancreatic cancer group and 46.7% in patients with cholangiocarcinoma, which was significantly greater than 13.3% in the healthy control group (p<0.05). An IHC analysis revealed that the TLR-4 protein expression in the SIBO-positive pancreatic carcinoma patients was significantly higher than that in the SIBO-negative patients (p<0.05), and the same result was in the cholangiocarcinoma subjects. In addition, a correlation analysis identified the positive relationship between the prevalence of SIBO and the TLR-4 protein expression in pancreatic carcinoma (r=0.489), and the same result was in the cholangiocarcinoma subjects. CONCLUSION: Our findings indicate a high prevalence of SIBO in pancreatic carcinoma and cholangiocarcinoma, and SIBO displays a positive correlation with the TLR-4 expression, suggesting that SIBO could be a risk factor for the pathogenesis of pancreatic carcinoma and cholangiocarcinoma, in which the TLR4 signaling may be involved.","Source":"PubMed","category":"HUMAN","training_data":"Association between small intestinal bacterial overgrowth and toll-like receptor 4 in patients with pancreatic carcinoma and cholangiocarcinoma BACKGROUND/AIMS: Multiple factors have been linked to pathogenesis of pancreatic cancer and cholangiocarcinoma. Until now, few studies have investigated the role of small intestinal bacterial overgrowth (SIBO) and toll-like receptor 4 (TLR-4) signaling in these diseases. This study aimed to examine the relationship between the prevalence of SIBO and the TLR-4 expression in patients with pancreatic carcinoma and cholangiocarcinoma. MATERIALS AND METHODS: A total of 90 human subjects suffering from pancreatic carcinoma (n=30), cholangiocarcinoma (n=30), and healthy controls (n=30) were enrolled in the study. A glucose hydrogen breath test (GHBT) was used to evaluate SIBO. The TLR4 protein expression was measured by immunohistochemistry (IHC). RESULTS: The positive rate of SIBO was 63.3% in the pancreatic cancer group and 46.7% in patients with cholangiocarcinoma, which was significantly greater than 13.3% in the healthy control group (p<0.05). An IHC analysis revealed that the TLR-4 protein expression in the SIBO-positive pancreatic carcinoma patients was significantly higher than that in the SIBO-negative patients (p<0.05), and the same result was in the cholangiocarcinoma subjects. In addition, a correlation analysis identified the positive relationship between the prevalence of SIBO and the TLR-4 protein expression in pancreatic carcinoma (r=0.489), and the same result was in the cholangiocarcinoma subjects. CONCLUSION: Our findings indicate a high prevalence of SIBO in pancreatic carcinoma and cholangiocarcinoma, and SIBO displays a positive correlation with the TLR-4 expression, suggesting that SIBO could be a risk factor for the pathogenesis of pancreatic carcinoma and cholangiocarcinoma, in which the TLR4 signaling may be involved. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological analysis prognosis extrahepatic bile duct cancer microscopic positive ductal margin background fate microscopic positive ductal margin mpdm extrahepatic bile duct ehbd cancer unclear purpose study analyse clinicopathological features ehbd cancer mpdm identify prognostic factors associated survival methods 1995 2007 retrospective analysis 464 patients undergone surgical resection ehbd cancer conducted clinicopathological factors likely influence survival assessed using univariate multivariate analysis results one hundred twenty four patients mpdm included invasive carcinoma ic n 85 carcinoma situ cis high grade dysplasia hgd n 39 median survival ms r0 r1 cis hgd r1 ic 41 months 29 months 18 months respectively adverse prognostic factors ic resection margin hr 1 66 95 confidence intervals cis 1 06 2 59 p 0 026 use adjuvant chemoradiotherapy hr 1 57 95 cis 1 04 2 39 p 0 033 adjuvant chemoradiotherapy beneficial patients mpdm ic 5 year survival rate 19 7 compared 2 8 p 0 011 conclusions presence mpdm important prognostic factor ehbd cancer ductal resection margin positive discrimination ic cis hgd important pubmed","probabilities":0.9799733,"Title":"Clinicopathological analysis and prognosis of extrahepatic bile duct cancer with a microscopic positive ductal margin","Abstract":"BACKGROUND: The fate of a microscopic positive ductal margin (MPDM) of extrahepatic bile duct (EHBD) cancer is unclear. The purpose of this study was to analyse the clinicopathological features of EHBD cancer with MPDM and to identify the prognostic factors associated with survival. METHODS: Between 1995 and 2007, a retrospective analysis of 464 patients who had undergone surgical resection for EHBD cancer was conducted. Clinicopathological factors likely to influence survival were assessed using univariate and multivariate analysis. RESULTS: One hundred twenty-four patients had MPDM which included invasive carcinoma (IC) (n =85) and carcinoma in situ (CIS)/ high-grade dysplasia (HGD) (n = 39). The median survival (MS) of R0, R1 as CIS/ HGD, and R1 as IC were 41 months, 29 months, and 18 months, respectively. Adverse prognostic factors were 'IC' on the resection margin [HR = 1.66, 95% confidence intervals (CIs) 1.06-2.59, P = 0.026], and no use of adjuvant chemoradiotherapy (HR = 1.57, 95% CIs 1.04-2.39, P = 0.033). Adjuvant chemoradiotherapy was beneficial in patients with MPDM as IC (5-year survival rate 19.7 compared with 2.8%, P = 0.011). CONCLUSIONS: The presence of MPDM is an important prognostic factor in EHBD cancer. When a ductal resection margin is positive, discrimination between 'IC' and 'CIS/ HGD' is important.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological analysis and prognosis of extrahepatic bile duct cancer with a microscopic positive ductal margin BACKGROUND: The fate of a microscopic positive ductal margin (MPDM) of extrahepatic bile duct (EHBD) cancer is unclear. The purpose of this study was to analyse the clinicopathological features of EHBD cancer with MPDM and to identify the prognostic factors associated with survival. METHODS: Between 1995 and 2007, a retrospective analysis of 464 patients who had undergone surgical resection for EHBD cancer was conducted. Clinicopathological factors likely to influence survival were assessed using univariate and multivariate analysis. RESULTS: One hundred twenty-four patients had MPDM which included invasive carcinoma (IC) (n =85) and carcinoma in situ (CIS)/ high-grade dysplasia (HGD) (n = 39). The median survival (MS) of R0, R1 as CIS/ HGD, and R1 as IC were 41 months, 29 months, and 18 months, respectively. Adverse prognostic factors were 'IC' on the resection margin [HR = 1.66, 95% confidence intervals (CIs) 1.06-2.59, P = 0.026], and no use of adjuvant chemoradiotherapy (HR = 1.57, 95% CIs 1.04-2.39, P = 0.033). Adjuvant chemoradiotherapy was beneficial in patients with MPDM as IC (5-year survival rate 19.7 compared with 2.8%, P = 0.011). CONCLUSIONS: The presence of MPDM is an important prognostic factor in EHBD cancer. When a ductal resection margin is positive, discrimination between 'IC' and 'CIS/ HGD' is important. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role preoperative therapy prior pancreatoduodenectomy distal cholangiocarcinoma background although increasingly administered patients pancreatic ductal adenocarcinoma role preoperative therapy patients distal cholangiocarcinoma undefined methods patients distal cholangiocarcinoma underwent pancreatoduodenectomy 1999 2014 retrospectively reviewed differences clinicopathologic characteristics overall survival os compared patients underwent surgery de novo received preoperative therapy results twenty one patients 46 7 received preoperative therapy 24 53 3 five year os rates statistically significantly different patients received preoperative therapy 46 6 vs 49 1 p 0 05 multivariate cox proportional hazards analysis lymph node positivity strongest predictor os hr 4 68 95 ci 1 52 14 42 whereas preoperative therapy associated improved os hr 1 06 95 ci 0 42 2 66 receipt either pre post operative therapy hr 0 40 95 ci 0 16 1 00 conclusion results support routine administration preoperative therapy patients distal cholangiocarcinoma may alternative treatment strategy appropriate subset patients high risk clinical pathologic features pubmed","probabilities":0.9799733,"Title":"The role of preoperative therapy prior to pancreatoduodenectomy for distal cholangiocarcinoma","Abstract":"BACKGROUND: Although increasingly administered to patients with pancreatic ductal adenocarcinoma, the role of preoperative therapy for patients with distal cholangiocarcinoma is undefined. METHODS: All patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy between 1999 and 2014 were retrospectively reviewed. Differences in clinicopathologic characteristics and overall survival (OS) were compared between patients who underwent surgery de novo and those who received preoperative therapy. RESULTS: Twenty-one patients (46.7%) received preoperative therapy and 24 (53.3%) did not. Five-year OS rates were not statistically significantly different between patients who received preoperative therapy and those who did not (46.6% vs 49.1%, p > 0.05). On multivariate cox proportional hazards analysis, lymph node positivity was the strongest predictor of OS (HR 4.68 (95%CI 1.52-14.42)). Whereas preoperative therapy was not associated with improved OS (HR 1.06 (95%CI 0.42-2.66)), the receipt of either pre- or post-operative therapy was (HR 0.40 (95%CI 0.16-1.00)). CONCLUSION: While these results do not support the routine administration of preoperative therapy to patients with distal cholangiocarcinoma, it may be an alternative treatment strategy appropriate for a subset of patients with high risk clinical or pathologic features.","Source":"PubMed","category":"HUMAN","training_data":"The role of preoperative therapy prior to pancreatoduodenectomy for distal cholangiocarcinoma BACKGROUND: Although increasingly administered to patients with pancreatic ductal adenocarcinoma, the role of preoperative therapy for patients with distal cholangiocarcinoma is undefined. METHODS: All patients with distal cholangiocarcinoma who underwent pancreatoduodenectomy between 1999 and 2014 were retrospectively reviewed. Differences in clinicopathologic characteristics and overall survival (OS) were compared between patients who underwent surgery de novo and those who received preoperative therapy. RESULTS: Twenty-one patients (46.7%) received preoperative therapy and 24 (53.3%) did not. Five-year OS rates were not statistically significantly different between patients who received preoperative therapy and those who did not (46.6% vs 49.1%, p > 0.05). On multivariate cox proportional hazards analysis, lymph node positivity was the strongest predictor of OS (HR 4.68 (95%CI 1.52-14.42)). Whereas preoperative therapy was not associated with improved OS (HR 1.06 (95%CI 0.42-2.66)), the receipt of either pre- or post-operative therapy was (HR 0.40 (95%CI 0.16-1.00)). CONCLUSION: While these results do not support the routine administration of preoperative therapy to patients with distal cholangiocarcinoma, it may be an alternative treatment strategy appropriate for a subset of patients with high risk clinical or pathologic features. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role postoperative adjuvant treatment advanced gallbladder cancer abstract available google scholar","probabilities":0.9799733,"Title":"Role Of Postoperative Adjuvant Treatment For Advanced Gallbladder Cancer","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Role Of Postoperative Adjuvant Treatment For Advanced Gallbladder Cancer Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"utility pre lt locoregional therapy hcc unos regions waiting time lt historically shorter background pre lt loco regional therapy lrt hcc practiced rationale prevent hcc progression waiting list however lrt expensive complications tace rfa carry complication rate 5 8 respectively possibility needle track seeding extra hepatic metastases studies also shown lrt t1 hcc associated increased lt waitlist mortality due worsening disease presumably related lrt offered additional post lt survival northup hepatology 09 issue becomes debatable lrt hcc considered unos regions waiting time lt historically shorter retrospectively reviewed outcomes lrt pre lt hcc following milan criteria center located unos region 3 waiting time lt historically shorter median waiting time 2003 04 49 days meld 19 24 methods retrospective review lt database since inception program 2005 identi ed 73 hcc lt hcc received pre lrt staging hcc lt followup 6 mth unless death occurred due hcc recurrence excluded lrt lrt cohorts compared test fisher exact tests patient survival estimated kaplan meier method results 56 hcc lt matched criteria 31 received tace pre lt lrt lrt groups statistically similar characteristics post lt 3 patients died hcc recurrence 1 incidental cholangiocarcinoma along hcc noted explant 1 diffuse hcc diagnosed imaging prior lt 1 lymh node invasion hcc however among lrt lrt groups hcc recurrence rate 1 3 5 yr survival probabilities statistically similar overall 1 3 5 yr survival rates hcc lt following milan criteria 98 94 84 respectively conclusions series additional bene observed lrt pre lt hcc following milan criteria considering associated cost complications prudence required utilization lrt pre lt hcc unos regions shorter waiting time google scholar","probabilities":0.9799733,"Title":"Utility Of Pre-Lt Locoregional Therapy For Hcc In Unos Regions Where Waiting Time For Lt Is Historically Shorter","Abstract":"Background: Pre-LT loco regional therapy [LRT] for HCC is practiced with a \nrationale to prevent HCC progression while on the waiting list. However, LRT is \nexpensive and has complications. TACE & RFA carry a complication rate of 5% \n& 8% respectively with the possibility of needle track seeding and extra-hepatic \nmetastases. Studies have also shown that LRT for T1 HCC was associated with increased LT waitlist mortality due to worsening disease presumably related to \nLRT, and offered no additional post-LT survival [Northup, Hepatology’09]. The \nissue becomes more debatable when LRT for HCC is considered in UNOS regions \nwhere waiting time for LT is historically shorter. We retrospectively reviewed the \noutcomes of LRT pre-LT for HCC following Milan criteria at our center located in \nUNOS region 3 where waiting time for LT is historically shorter [median waiting \ntime during 2003-04 = 49 days for a MELD 19-24].\nMethods: Retrospective review of our LT database since the inception of the program \n[2005] identifi ed 73 HCC-LT. HCC that received pre-LRT for down staging, and \nHCC-LT with a followup of <6 mth unless death occurred due to HCC recurrence \nwere excluded. LRT and no-LRT cohorts were compared by t-test & Fisher’s exact \ntests; patient survival was estimated by Kaplan-Meier method.\nResults: 56 HCC-LT matched the criteria. 31 received TACE pre-LT. LRT & no-LRT \ngroups were statistically similar in characteristics. Post LT, 3 patients died from HCC \nrecurrence: 1-incidental cholangiocarcinoma along with HCC noted on the explant; \n1-diffuse HCC not diagnosed by imaging prior to LT; 1-lymh node invasion by HCC. \nHowever, among the LRT and no-LRT groups, HCC recurrence rate and 1-, 3- and \n5-yr survival probabilities were statistically similar The overall 1-, 3- and 5-yr survival rates [%] for HCC-LT following Milan criteria \nwere 98, 94 and 84 respectively.\nConclusions: In our series no additional benefi t was observed with LRT pre-LT for \nHCC following Milan criteria. Considering the associated cost & complications \nprudence is required in utilization of LRT pre-LT for HCC in UNOS regions with \na shorter waiting time.","Source":"Google Scholar","category":"HUMAN","training_data":"Utility Of Pre-Lt Locoregional Therapy For Hcc In Unos Regions Where Waiting Time For Lt Is Historically Shorter Background: Pre-LT loco regional therapy [LRT] for HCC is practiced with a \nrationale to prevent HCC progression while on the waiting list. However, LRT is \nexpensive and has complications. TACE & RFA carry a complication rate of 5% \n& 8% respectively with the possibility of needle track seeding and extra-hepatic \nmetastases. Studies have also shown that LRT for T1 HCC was associated with increased LT waitlist mortality due to worsening disease presumably related to \nLRT, and offered no additional post-LT survival [Northup, Hepatology’09]. The \nissue becomes more debatable when LRT for HCC is considered in UNOS regions \nwhere waiting time for LT is historically shorter. We retrospectively reviewed the \noutcomes of LRT pre-LT for HCC following Milan criteria at our center located in \nUNOS region 3 where waiting time for LT is historically shorter [median waiting \ntime during 2003-04 = 49 days for a MELD 19-24].\nMethods: Retrospective review of our LT database since the inception of the program \n[2005] identifi ed 73 HCC-LT. HCC that received pre-LRT for down staging, and \nHCC-LT with a followup of <6 mth unless death occurred due to HCC recurrence \nwere excluded. LRT and no-LRT cohorts were compared by t-test & Fisher’s exact \ntests; patient survival was estimated by Kaplan-Meier method.\nResults: 56 HCC-LT matched the criteria. 31 received TACE pre-LT. LRT & no-LRT \ngroups were statistically similar in characteristics. Post LT, 3 patients died from HCC \nrecurrence: 1-incidental cholangiocarcinoma along with HCC noted on the explant; \n1-diffuse HCC not diagnosed by imaging prior to LT; 1-lymh node invasion by HCC. \nHowever, among the LRT and no-LRT groups, HCC recurrence rate and 1-, 3- and \n5-yr survival probabilities were statistically similar The overall 1-, 3- and 5-yr survival rates [%] for HCC-LT following Milan criteria \nwere 98, 94 and 84 respectively.\nConclusions: In our series no additional benefi t was observed with LRT pre-LT for \nHCC following Milan criteria. Considering the associated cost & complications \nprudence is required in utilization of LRT pre-LT for HCC in UNOS regions with \na shorter waiting time. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"strategy treatment mid distal cholangiocarcinoma surgical resection overall survival os rate extrahepatic cholangiocarcinoma ecc remains much lower gastrointestinal malignancies variety factors used predict prognosis surgical resection ecc consensus reached therefore study sought identify useful prognostic factors patients ecc institution within study period 76 patients received surgical resection mid distal cholangiocarcinoma clinicopathological data retrospectively collected along survival prognosis multivariate analysis os ductal margin status p 0 008 pt category p 0 02 presented independent predictors survival r0 resection group n stage adjuvant chemotherapy presented independent predictors recurrence multivariate model three five year survival rates significantly better patients negative ductal margins 77 three years 63 6 five years positive ductal margins 33 3 three years 25 0 five years p 0 05 survival rates similar cases r0 resection without gemcitabine based chemotherapy r1 resection gemcitabine based chemotherapy p 0 6193 log rank test however survival rates r0 resection gemcitabine based chemotherapy r1 resection gemcitabine based chemotherapy significantly different p 0 0086 log rank test good prognosis radical resection ensure adequate margin may recommended middle common bile duct cancer addition regardless margin negativity gemcitabine based chemotherapy recommended prolongation relapse free time os time pubmed","probabilities":0.9799733,"Title":"The Strategy of Treatment for Mid to Distal Cholangiocarcinoma after Surgical Resection","Abstract":"The overall survival (OS) rate of extrahepatic cholangiocarcinoma (ECC) remains much lower than that for other gastrointestinal malignancies. A variety of factors have been used to predict prognosis after surgical resection for ECC, but no consensus has been reached. Therefore, this study sought to identify useful prognostic factors for patients with ECC. In our institution, within the study period, 76 patients received surgical resection for mid to distal cholangiocarcinoma. Clinicopathological data were retrospectively collected, along with survival and prognosis. In multivariate analysis for OS, ductal margin status (P = 0.008) and pT category (P < 0.02) presented independent predictors of survival. In the R0 resection group, N stage and adjuvant chemotherapy presented independent predictors of recurrence in the multivariate model. The three- and five-year survival rates were significantly better in patients with negative ductal margins (77.% at three years and 63.6% at five years) than in those with positive ductal margins (33.3% at three years and 25.0% at five years) (P < 0.05). Survival rates were similar between cases of R0 resection without gemcitabine-based chemotherapy and R1 resection with gemcitabine-based chemotherapy (P = 0.6193, Log-rank test). However, survival rates between R0 resection with gemcitabine-based chemotherapy and R1 resection with gemcitabine-based chemotherapy were significantly different (P = 0.0086, Log-rank test). For good prognosis, radical resection to ensure adequate margin may be recommended for middle common bile duct cancer. In addition, regardless of margin negativity, gemcitabine-based chemotherapy is recommended for prolongation of relapse-free time and OS time.","Source":"PubMed","category":"HUMAN","training_data":"The Strategy of Treatment for Mid to Distal Cholangiocarcinoma after Surgical Resection The overall survival (OS) rate of extrahepatic cholangiocarcinoma (ECC) remains much lower than that for other gastrointestinal malignancies. A variety of factors have been used to predict prognosis after surgical resection for ECC, but no consensus has been reached. Therefore, this study sought to identify useful prognostic factors for patients with ECC. In our institution, within the study period, 76 patients received surgical resection for mid to distal cholangiocarcinoma. Clinicopathological data were retrospectively collected, along with survival and prognosis. In multivariate analysis for OS, ductal margin status (P = 0.008) and pT category (P < 0.02) presented independent predictors of survival. In the R0 resection group, N stage and adjuvant chemotherapy presented independent predictors of recurrence in the multivariate model. The three- and five-year survival rates were significantly better in patients with negative ductal margins (77.% at three years and 63.6% at five years) than in those with positive ductal margins (33.3% at three years and 25.0% at five years) (P < 0.05). Survival rates were similar between cases of R0 resection without gemcitabine-based chemotherapy and R1 resection with gemcitabine-based chemotherapy (P = 0.6193, Log-rank test). However, survival rates between R0 resection with gemcitabine-based chemotherapy and R1 resection with gemcitabine-based chemotherapy were significantly different (P = 0.0086, Log-rank test). For good prognosis, radical resection to ensure adequate margin may be recommended for middle common bile duct cancer. In addition, regardless of margin negativity, gemcitabine-based chemotherapy is recommended for prolongation of relapse-free time and OS time. PubMed","prediction_labels":"HUMAN"},{"cleaned":"trends surgery disparities receipt surgery intrahepatic cholangiocarcinoma us 2005 2014 background intrahepatic cholangiocarcinoma ihc malignancy increasing incidence surgery treatment modality associated long term survival objective study utilize nationwide representative database quantify trends incidence surgery ihc united states 2004 2014 well identify disparities receipt surgery methods patients admitted diagnosis ihc 2005 2014 identified nationwide inpatient sample nis database trends number ihc admissions surgery procedures well outcomes examined multivariate analysis used determine effects demographic clinical co variables resection rates results estimated total 104 045 ihc related admissions occurred 2005 2014 hospitalization rate ihc increased nearly 2 fold 2014 38 9 per 100 000 95 ci 35 7 42 2 18 1 per 100 000 95 ci 15 8 20 3 2005 liver resections increased 248 p 0 01 increasing majority performed teaching hospitals 56 minor resections increase estimated hospital charges 87 124 148 613 p 0 001 decrease los 12 days 10 days p 0 01 inpatient mortality ihc decreased significantly 11 8 4 p 0 004 year 2005 2014 respectively age 80 years 0 45 95 ci 0 33 0 60 black race 0 50 95 ci 0 39 063 hispanic race 0 59 95 ci 0 45 0 79 medicaid insurance 0 58 95 ci 0 42 0 79 elixhauser comorbidity score 3 0 58 95 ci 0 47 0 73 associated decreased rates resection conclusions overall hospitalization volume surgery ihc increased dramatically past decade increase cost decrease los inpatient mortality period socioeconomic racial disparities observed receipt surgery ihc additional work needed understand complex interplay socioeconomic status race treatment ihc stn","probabilities":0.9799733,"Title":"Trends In Surgery And Disparities In Receipt Of Surgery For Intrahepatic Cholangiocarcinoma In The Us: 2005-2014","Abstract":"Background: Intrahepatic cholangiocarcinoma (IHC) is a malignancy with an increasing incidence. Surgery is the only treatment modality associated with long term survival. The objective of this study is to utilize a nationwide representative database to quantify the trends in incidence, and surgery for IHC in the United States from 2004-2014, as well as identify any disparities in the receipt of surgery. \r\n\r\n Methods: All patients admitted with a diagnosis of IHC between 2005 and 2014 were identified from the Nationwide Inpatient Sample (NIS) database. Trends in the number of IHC admissions and surgery procedures as well as outcomes were examined, and a multivariate analysis was used to determine the effects of demographic and clinical co-variables on resection rates. \r\n\r\n Results: An estimated total of 104,045 IHC related admissions occurred between 2005 and 2014. The hospitalization rate for IHC increased by nearly 2-fold in 2014 [38.9 per 100,000 (95% CI, 35.7-42.2)] from 18.1 per 100,000 (95% CI, 15.8-20.3) in 2005. Liver resections increased 248% (P<0.01) with an increasing majority being performed at teaching hospitals and 56% being minor resections. There was an increase in estimated hospital charges from $87,124 to $148,613 (P<0.001) and decrease in LOS from 12 days to 10 days (P<0.01). Inpatient mortality for IHC decreased significantly from 11% to 8.4% (P=0.004), from year 2005 to 2014 respectively. Age >80 years (OR =0.45; 95% CI, 0.33-0.60), Black race (OR =0.50; 95% CI, 0.39-063), Hispanic race (OR =0.59; 95% CI, 0.45-0.79), Medicaid insurance (OR =0.58; 95% CI, 0.42-0.79) and Elixhauser comorbidity score >3 (OR =0.58; 95% CI, 0.47-0.73) were associated with decreased rates of resection. \r\n\r\n Conclusions: Overall hospitalization and volume of surgery for IHC has increased dramatically over the past decade. There has been an increase in cost, decrease in LOS and inpatient mortality during the period. Socioeconomic and racial disparities were observed in the receipt of surgery for IHC. Additional work is needed to understand the complex interplay between socioeconomic status and race in in the treatment of IHC.","Source":"STN","category":"HUMAN","training_data":"Trends In Surgery And Disparities In Receipt Of Surgery For Intrahepatic Cholangiocarcinoma In The Us: 2005-2014 Background: Intrahepatic cholangiocarcinoma (IHC) is a malignancy with an increasing incidence. Surgery is the only treatment modality associated with long term survival. The objective of this study is to utilize a nationwide representative database to quantify the trends in incidence, and surgery for IHC in the United States from 2004-2014, as well as identify any disparities in the receipt of surgery. \r\n\r\n Methods: All patients admitted with a diagnosis of IHC between 2005 and 2014 were identified from the Nationwide Inpatient Sample (NIS) database. Trends in the number of IHC admissions and surgery procedures as well as outcomes were examined, and a multivariate analysis was used to determine the effects of demographic and clinical co-variables on resection rates. \r\n\r\n Results: An estimated total of 104,045 IHC related admissions occurred between 2005 and 2014. The hospitalization rate for IHC increased by nearly 2-fold in 2014 [38.9 per 100,000 (95% CI, 35.7-42.2)] from 18.1 per 100,000 (95% CI, 15.8-20.3) in 2005. Liver resections increased 248% (P<0.01) with an increasing majority being performed at teaching hospitals and 56% being minor resections. There was an increase in estimated hospital charges from $87,124 to $148,613 (P<0.001) and decrease in LOS from 12 days to 10 days (P<0.01). Inpatient mortality for IHC decreased significantly from 11% to 8.4% (P=0.004), from year 2005 to 2014 respectively. Age >80 years (OR =0.45; 95% CI, 0.33-0.60), Black race (OR =0.50; 95% CI, 0.39-063), Hispanic race (OR =0.59; 95% CI, 0.45-0.79), Medicaid insurance (OR =0.58; 95% CI, 0.42-0.79) and Elixhauser comorbidity score >3 (OR =0.58; 95% CI, 0.47-0.73) were associated with decreased rates of resection. \r\n\r\n Conclusions: Overall hospitalization and volume of surgery for IHC has increased dramatically over the past decade. There has been an increase in cost, decrease in LOS and inpatient mortality during the period. Socioeconomic and racial disparities were observed in the receipt of surgery for IHC. Additional work is needed to understand the complex interplay between socioeconomic status and race in in the treatment of IHC. STN","prediction_labels":"HUMAN"},{"cleaned":"surgery adjuvant therapy gallbladder cancer single institution experience background gallbladder cancer highly fatal disease high rate recurrence even diagnosed early stage relative rarity currently established algorithms guide therapy cholecystectomy explore value adjuvant therapy chemotherapy radiation evaluated patients resected gallbladder cancer treated institution methods patients diagnosed gallbladder cancer underwent cholecystectomy simple radical 2000 2010 identified using cancer registry retrospective chart review performed clinicopathologic data including age stage grade type surgery margin status type duration adjuvant therapy primary endpoint overall survival os univariate uva multivariate mva analysis performed cox logistic regression analyses results identified 73 patients median followup patients 28 2 months majority patients female 74 underwent radical cholecystectomy 64 positive margins adjuvant radiation therapy documented 21 37 respectively majority patients receive adjuvant therapy 53 4 median os patients 41 3 months survival benefit associated patients undergoing radical cholecystectomy followed adjuvant radiation median os 48 4 months vs 22 3 months hr 0 35 95 ci 0 13 0 98 p 0 0448 compared simple cholecystectomy alone uva increasing age positive margins significantly associated worse os radical cholecystectomy associated improved os mva increasing age male gender poorly differentiated tumor positive margins associated worse os adjuvant radiation associated improved os p 0 0113 conclusions analysis supports role adjuvant radiation therapy resected gallbladder cancer multi institutional prospective studies performed evaluate optimal treatment strategy biomarker analysis might also help determine subset patients benefit combined chemoradiation google scholar","probabilities":0.9799733,"Title":"Surgery And Adjuvant Therapy In Gallbladder Cancer: A Single-Institution Experience","Abstract":"Background: Gallbladder cancer is a highly fatal disease with a high rate of recurrence even when diagnosed at an early stage. Because of its relative rarity, there are currently no established algorithms to guide therapy after cholecystectomy. To explore the value of adjuvant therapy with chemotherapy and radiation, we evaluated patients with resected gallbladder cancer treated at our institution. Methods: Patients diagnosed with gallbladder cancer who underwent cholecystectomy (simple or radical) between 2000 and 2010 were identified using our cancer registry. Retrospective chart review was performed for clinicopathologic data, including age, stage, grade, type of surgery, margin status, and type and duration of adjuvant therapy. The primary endpoint was overall survival (OS). Univariate (UVA) and multivariate (MVA) analysis was performed with Cox logistic regression analyses. Results: We identified 73 patients with a median followup for all patients of 28.2 months. The majority of patients were female (74%) and underwent radical cholecystectomy (64%). Positive margins and adjuvant radiation therapy were documented in 21% and 37%, respectively. The majority of patients did not receive any adjuvant therapy (53.4%). Median OS for all patients was 41.3 months. There was a survival benefit associated with patients undergoing radical cholecystectomy followed by adjuvant radiation (median OS 48.4 months vs. 22.3 months; HR 0.35; 95% CI: 0.13–0.98; p=0.0448) compared to simple cholecystectomy alone. On UVA, increasing age and positive margins were significantly associated with worse OS, while radical cholecystectomy was associated with improved OS. On MVA, increasing age, male gender, poorly differentiated tumor, and positive margins were associated with worse OS, while adjuvant radiation was associated with improved OS (p=0.0113). Conclusions: Our analysis supports the role for adjuvant radiation therapy in resected gallbladder cancer. Multi-institutional prospective studies should be performed to evaluate the optimal treatment strategy. Biomarker analysis might also help determine the subset of patients who would benefit from combined chemoradiation.","Source":"Google Scholar","category":"HUMAN","training_data":"Surgery And Adjuvant Therapy In Gallbladder Cancer: A Single-Institution Experience Background: Gallbladder cancer is a highly fatal disease with a high rate of recurrence even when diagnosed at an early stage. Because of its relative rarity, there are currently no established algorithms to guide therapy after cholecystectomy. To explore the value of adjuvant therapy with chemotherapy and radiation, we evaluated patients with resected gallbladder cancer treated at our institution. Methods: Patients diagnosed with gallbladder cancer who underwent cholecystectomy (simple or radical) between 2000 and 2010 were identified using our cancer registry. Retrospective chart review was performed for clinicopathologic data, including age, stage, grade, type of surgery, margin status, and type and duration of adjuvant therapy. The primary endpoint was overall survival (OS). Univariate (UVA) and multivariate (MVA) analysis was performed with Cox logistic regression analyses. Results: We identified 73 patients with a median followup for all patients of 28.2 months. The majority of patients were female (74%) and underwent radical cholecystectomy (64%). Positive margins and adjuvant radiation therapy were documented in 21% and 37%, respectively. The majority of patients did not receive any adjuvant therapy (53.4%). Median OS for all patients was 41.3 months. There was a survival benefit associated with patients undergoing radical cholecystectomy followed by adjuvant radiation (median OS 48.4 months vs. 22.3 months; HR 0.35; 95% CI: 0.13–0.98; p=0.0448) compared to simple cholecystectomy alone. On UVA, increasing age and positive margins were significantly associated with worse OS, while radical cholecystectomy was associated with improved OS. On MVA, increasing age, male gender, poorly differentiated tumor, and positive margins were associated with worse OS, while adjuvant radiation was associated with improved OS (p=0.0113). Conclusions: Our analysis supports the role for adjuvant radiation therapy in resected gallbladder cancer. Multi-institutional prospective studies should be performed to evaluate the optimal treatment strategy. Biomarker analysis might also help determine the subset of patients who would benefit from combined chemoradiation. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"impact microvascular invasion clinical outcomes curative intent resection intrahepatic cholangiocarcinoma background microvascular invasion mivi histological feature intrahepatic cholangiocarcinoma icc may associated biological behavior sought investigate impact mivi long term survival patients undergoing curative intent resection icc methods total 1089 patients undergoing curative intent resection icc identified data clinicopathological characteristics disease free survival dfs overall survival os compared among patients vascular invasion novi mivi macrovascular invasion mavi results total 249 22 9 patients mivi 149 13 7 patients mavi mivi mivi associated higher incidence perineural biliary adjacent organ invasion satellite lesions p 0 01 multivariable analysis mivi independent risk factor dfs hazard ratios hr 1 5 95 confidence intervals ci 1 3 1 9 p 0 001 os hr 1 1 95 ci 0 9 1 3 p 0 379 mivi mavi patients similar dfs median mivi 14 0 vs mavi 12 0 months hr 0 9 95 ci 0 7 1 2 p 0 377 os better among mivi patients median mivi 39 0 vs mavi 21 0 months hr 0 7 95 ci 0 5 0 8 p 0 002 whereas nodal metastasis r1 margin postoperative morbidity associated early death 18 months among patients mivi nodal metastasis associated late 18 months prognosis conclusions roughly 1 5 patients resected icc mivi mivi associated advanced tumor characteristics higher risk tumor recurrence pubmed","probabilities":0.9799733,"Title":"Impact of microvascular invasion on clinical outcomes after curative-intent resection for intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Microvascular invasion (MiVI) is a histological feature of intrahepatic cholangiocarcinoma (ICC) that may be associated with biological behavior. We sought to investigate the impact of MiVI on long-term survival of patients undergoing curative-intent resection for ICC. METHODS: A total of 1089 patients undergoing curative-intent resection for ICC were identified. Data on clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) were compared among patients with no vascular invasion (NoVI), MiVI, and macrovascular invasion (MaVI). RESULTS: A total of 249 (22.9%) patients had MiVI, while 149 (13.7%) patients had MaVI (±MiVI). MiVI was associated with higher incidence of perineural, biliary and adjacent organ invasion, and satellite lesions (all P < 0.01). On multivariable analysis, MiVI was an independent risk factor of DFS (hazard ratios [HR] 1.5; 95%confidence intervals [CI], 1.3-1.9; P < 0.001), but not OS (HR 1.1; 95%CI, 0.9-1.3; P = 0.379). While MiVI and MaVI patients had similar DFS (median, MiVI 14.0 vs MaVI 12.0 months, HR 0.9; 95%CI, 0.7-1.2; P = 0.377), OS was better among MiVI patients (median, MiVI 39.0 vs MaVI 21.0 months, HR 0.7; 95%CI, 0.5-0.8; P = 0.002). Whereas nodal metastasis, R1 margin, and postoperative morbidity were associated with early death (≤18 months) among patients with MiVI, only nodal metastasis was associated with late (>18 months) prognosis. CONCLUSIONS: Roughly 1 out of 5 patients with resected ICC had MiVI. MiVI was associated with advanced tumor characteristics and a higher risk of tumor recurrence.","Source":"PubMed","category":"HUMAN","training_data":"Impact of microvascular invasion on clinical outcomes after curative-intent resection for intrahepatic cholangiocarcinoma BACKGROUND: Microvascular invasion (MiVI) is a histological feature of intrahepatic cholangiocarcinoma (ICC) that may be associated with biological behavior. We sought to investigate the impact of MiVI on long-term survival of patients undergoing curative-intent resection for ICC. METHODS: A total of 1089 patients undergoing curative-intent resection for ICC were identified. Data on clinicopathological characteristics, disease-free survival (DFS), and overall survival (OS) were compared among patients with no vascular invasion (NoVI), MiVI, and macrovascular invasion (MaVI). RESULTS: A total of 249 (22.9%) patients had MiVI, while 149 (13.7%) patients had MaVI (±MiVI). MiVI was associated with higher incidence of perineural, biliary and adjacent organ invasion, and satellite lesions (all P < 0.01). On multivariable analysis, MiVI was an independent risk factor of DFS (hazard ratios [HR] 1.5; 95%confidence intervals [CI], 1.3-1.9; P < 0.001), but not OS (HR 1.1; 95%CI, 0.9-1.3; P = 0.379). While MiVI and MaVI patients had similar DFS (median, MiVI 14.0 vs MaVI 12.0 months, HR 0.9; 95%CI, 0.7-1.2; P = 0.377), OS was better among MiVI patients (median, MiVI 39.0 vs MaVI 21.0 months, HR 0.7; 95%CI, 0.5-0.8; P = 0.002). Whereas nodal metastasis, R1 margin, and postoperative morbidity were associated with early death (≤18 months) among patients with MiVI, only nodal metastasis was associated with late (>18 months) prognosis. CONCLUSIONS: Roughly 1 out of 5 patients with resected ICC had MiVI. MiVI was associated with advanced tumor characteristics and a higher risk of tumor recurrence. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic assessment three single nucleotide polymorphisms gnb3 825c bcl2 938c mcl1 386c g extrahepatic cholangiocarcinoma background aims cholangiocellular carcinoma cca devastating prognosis markers enabling precise prediction clinical outcome long remained scarce recently demonstrated genotype distribution several single nucleotide polymorphisms snps genes modulate g protein signal transduction apoptosis serve helpful predictive parameters various carcinomas aimed extending panel snps suitable predicting outcome cca methodology forty caucasian patients extrahepatic cca 40 age sex matched healthy white caucasians genotyped elucidate putative associations clinical outcome genotypes three following snps g protein beta 3 gnb3 825c b cell lymphoma 2 bcl 2 938c myeloid cell leukemia 1 mcl 1 386c g results patients homozygous c allele gnb3 825c polymorphism exhibited significant prolonged overall survival compared patients displaying ct tt genotype median survival months 31 vs 13 vs 7 p 05 also showed lower bilirubin serum levels additionally cc genotype bcl2 938c polymorphism associated higher gldh serum activities u l 29 8 7 1 vs 11 4 4 3 vs 5 6 1 7 comparing cc vs ca vs aa p 05 genotype distributions snps significantly different patients vs controls conclusions gnb3 825c snp may novel independent prognostic marker patients suffering extrahepatic cca cc genotype associated favorable clinical outcome prospective studies needed confirm results reveal additional functional snp effects pubmed","probabilities":0.962963,"Title":"Prognostic assessment of three single-nucleotide polymorphisms (GNB3 825C>T, BCL2-938C>A, MCL1-386C>G) in extrahepatic cholangiocarcinoma","Abstract":"BACKGROUND/AIMS: Cholangiocellular carcinoma (CCA) has a devastating prognosis and markers enabling a precise prediction of the clinical outcome have long remained scarce. Recently, it has been demonstrated that genotype distribution of several single-nucleotide polymorphisms (SNPs) in genes that modulate G protein-signal transduction and apoptosis can serve as helpful predictive parameters in various carcinomas. We here aimed at extending the panel of SNPs suitable for predicting the outcome of CCA. METHODOLOGY: Forty Caucasian patients with extrahepatic CCA and 40 age- and sex-matched healthy white Caucasians were genotyped to elucidate putative associations between clinical outcome and genotypes of the three following SNPs: G protein beta 3 (GNB3) 825C>T, B-cell-lymphoma-2 (Bcl-2) -938C>A, and myeloid cell leukemia-1 (Mcl-1) -386C>G. RESULTS: Patients homozygous for the C allele of the GNB3 825C>T polymorphism exhibited a significant prolonged overall survival compared with patients displaying the CT or TT genotype (median survival [months]: 31 vs. 13 vs. 7; p < .05) and also showed lower bilirubin serum levels. Additionally, the CC genotype of the BCL2-938C>A polymorphism was associated with higher GLDH serum activities (U/l; 29.8 +/- 7.1 vs. 11.4 +/- 4.3 vs. 5.6 +/- 1.7 comparing CC vs. CA vs. AA; p < .05). Genotype distributions for all SNPs were not significantly different in patients vs. controls. CONCLUSIONS: GNB3 825C>T SNP may be a novel independent prognostic marker for patients suffering from extrahepatic CCA with the CC genotype to be associated with a favorable clinical outcome. Further prospective studies are needed to confirm these results and reveal additional functional SNP effects.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic assessment of three single-nucleotide polymorphisms (GNB3 825C>T, BCL2-938C>A, MCL1-386C>G) in extrahepatic cholangiocarcinoma BACKGROUND/AIMS: Cholangiocellular carcinoma (CCA) has a devastating prognosis and markers enabling a precise prediction of the clinical outcome have long remained scarce. Recently, it has been demonstrated that genotype distribution of several single-nucleotide polymorphisms (SNPs) in genes that modulate G protein-signal transduction and apoptosis can serve as helpful predictive parameters in various carcinomas. We here aimed at extending the panel of SNPs suitable for predicting the outcome of CCA. METHODOLOGY: Forty Caucasian patients with extrahepatic CCA and 40 age- and sex-matched healthy white Caucasians were genotyped to elucidate putative associations between clinical outcome and genotypes of the three following SNPs: G protein beta 3 (GNB3) 825C>T, B-cell-lymphoma-2 (Bcl-2) -938C>A, and myeloid cell leukemia-1 (Mcl-1) -386C>G. RESULTS: Patients homozygous for the C allele of the GNB3 825C>T polymorphism exhibited a significant prolonged overall survival compared with patients displaying the CT or TT genotype (median survival [months]: 31 vs. 13 vs. 7; p < .05) and also showed lower bilirubin serum levels. Additionally, the CC genotype of the BCL2-938C>A polymorphism was associated with higher GLDH serum activities (U/l; 29.8 +/- 7.1 vs. 11.4 +/- 4.3 vs. 5.6 +/- 1.7 comparing CC vs. CA vs. AA; p < .05). Genotype distributions for all SNPs were not significantly different in patients vs. controls. CONCLUSIONS: GNB3 825C>T SNP may be a novel independent prognostic marker for patients suffering from extrahepatic CCA with the CC genotype to be associated with a favorable clinical outcome. Further prospective studies are needed to confirm these results and reveal additional functional SNP effects. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cisplatin gemcitabine patients advanced biliary tract cancer abc persistent jaundice despite optimal stenting effective intervention patients luminal disease introduction advanced biliary tract cancer abc 02 study established cisplatin gemcitabine cisgem reference 1 st line regimen patients advanced metastatic biliary tract cancer patients bilirubin 1 5 upper limit normal uln excluded extant data systemic treatment context elevated bilirubin methods patients abc receiving cisgem baseline bilirubin 1 5 uln eligible retrospective analysis response toxicity survival data collected results thirty three patients 545 screened median age 59 years range 23 79 58 male 58 metastases 79 liver performance status ps 0 33 1 64 2 3 eligible median baseline bilirubin 55 mol l range 32 286 due biliary tract obstruction bto 76 liver metastases lm 24 toxicity comparable abc 02 study bilirubin normalised 64 chemotherapy follow median progression free survival pfs 6 9 months 95 confidence interval ci 4 4 9 0 median overall survival os 9 5 months 95 ci 5 7 12 8 patients bto longer pfs os lm 7 0 versus 2 6 months p 0 1633 9 8 versus 4 4 months hazard ratio hr 0 74 p 0 465 respectively statistically significant due small sample size normalisation bilirubin completion eight cisgem cycles associated longer os 11 4 versus 2 9 months hr 0 49 p 0 08 15 2 versus 5 4 months hr 0 12 p 0 001 respectively difference os shown bilirubin percentiles either pfs os conclusion ps 0 1 patients abc high bilirubin due luminal disease despite optimal stenting cisgem used safely results similar patients normal bilirubin pubmed","probabilities":0.9799733,"Title":"Cisplatin and gemcitabine in patients with advanced biliary tract cancer (ABC) and persistent jaundice despite optimal stenting: Effective intervention in patients with luminal disease","Abstract":"INTRODUCTION: The advanced biliary tract cancer (ABC)-02 study established cisplatin and gemcitabine (CisGem) as a reference 1(st)-line regimen for patients with advanced/metastatic biliary tract cancer; patients with bilirubin ⩾ 1.5 × upper limit of normal (ULN) were excluded and there are few extant data for systemic treatment in the context of elevated bilirubin. METHODS: Patients with ABC, receiving CisGem with a baseline bilirubin of ⩾ 1.5 × ULN were eligible for this retrospective analysis; response, toxicity and survival data were collected. RESULTS: Thirty-three patients of 545 screened; median age 59 years, range 23-79; 58% male, 58% with metastases (79% in the liver) of performance status (PS) 0 (33%), 1 (64%) or 2 (3%) were eligible. The median baseline bilirubin was 55 μmol/L (range 32-286); due to biliary tract obstruction (BTO, 76%) or liver metastases (LM, 24%). Toxicity was comparable to the ABC-02 study; bilirubin normalised in 64% during chemotherapy/follow-up. The median progression-free survival (PFS) was 6.9 months (95% confidence interval (CI): 4.4-9.0) and median overall survival (OS) 9.5 months (95% CI: 5.7-12.8). Patients with BTO had a longer PFS and OS than those with LM (7.0 versus 2.6 months; p = 0.1633 and 9.8 versus 4.4 months, hazard ratio (HR) 0.74; p = 0.465, respectively); not statistically significant (due to small sample size). Normalisation of bilirubin and completion of eight CisGem cycles were associated with longer OS (11.4 versus 2.9 months, HR 0.49; p = 0.08 and 15.2 versus 5.4 months, HR 0.12 p < 0.001, respectively). No difference in OS was shown between the bilirubin percentiles (for either PFS or OS). CONCLUSION: For PS 0-1 patients with ABC and high bilirubin due to luminal disease despite optimal stenting CisGem can be used safely with results similar to those in patients with normal bilirubin.","Source":"PubMed","category":"HUMAN","training_data":"Cisplatin and gemcitabine in patients with advanced biliary tract cancer (ABC) and persistent jaundice despite optimal stenting: Effective intervention in patients with luminal disease INTRODUCTION: The advanced biliary tract cancer (ABC)-02 study established cisplatin and gemcitabine (CisGem) as a reference 1(st)-line regimen for patients with advanced/metastatic biliary tract cancer; patients with bilirubin ⩾ 1.5 × upper limit of normal (ULN) were excluded and there are few extant data for systemic treatment in the context of elevated bilirubin. METHODS: Patients with ABC, receiving CisGem with a baseline bilirubin of ⩾ 1.5 × ULN were eligible for this retrospective analysis; response, toxicity and survival data were collected. RESULTS: Thirty-three patients of 545 screened; median age 59 years, range 23-79; 58% male, 58% with metastases (79% in the liver) of performance status (PS) 0 (33%), 1 (64%) or 2 (3%) were eligible. The median baseline bilirubin was 55 μmol/L (range 32-286); due to biliary tract obstruction (BTO, 76%) or liver metastases (LM, 24%). Toxicity was comparable to the ABC-02 study; bilirubin normalised in 64% during chemotherapy/follow-up. The median progression-free survival (PFS) was 6.9 months (95% confidence interval (CI): 4.4-9.0) and median overall survival (OS) 9.5 months (95% CI: 5.7-12.8). Patients with BTO had a longer PFS and OS than those with LM (7.0 versus 2.6 months; p = 0.1633 and 9.8 versus 4.4 months, hazard ratio (HR) 0.74; p = 0.465, respectively); not statistically significant (due to small sample size). Normalisation of bilirubin and completion of eight CisGem cycles were associated with longer OS (11.4 versus 2.9 months, HR 0.49; p = 0.08 and 15.2 versus 5.4 months, HR 0.12 p < 0.001, respectively). No difference in OS was shown between the bilirubin percentiles (for either PFS or OS). CONCLUSION: For PS 0-1 patients with ABC and high bilirubin due to luminal disease despite optimal stenting CisGem can be used safely with results similar to those in patients with normal bilirubin. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence rate gallbladder cancer japanese japan united states cancer incidence five continents order make comparison gallbladder cancer incidence rates japanese japan usa abstracted age standardized incidence rates asrs cancer incidence five continents vol x ci5 international agency research cancer provides ci5 databases incidence cancer recorded cancer registries regional national worldwide used asrs japanese following cancer registries miyagi nagasaki osaka japan california los angeles california san francisco hawaii usa ci5 database furthermore referred asrs usa seer 9 registries hawaii years cancer diagnosis 1959 2007 volume x ci5 however years little different registries figure 1 shows asrs gallbladder cancers coded c23 24 icd10 males asrs three japanese registries tended higher white black us registries asrs japanese us registries intermediate asrs japan showed peak around vol 8 mid 1990s decreasing trend thereafter asrs usa showed slow decreasing trend observation period figure 2 shows asrs gallbladder cancers females overall pattern similar observed males asrs japanese us registries close white black us registries peak asr japan slightly earlier observed males one registry nagasaki show clear peak google scholar","probabilities":0.9799733,"Title":"Incidence Rate For Gallbladder Cancer In Japanese In Japan And In The United States From The Cancer Incidence In Five Continents","Abstract":"In order to make a comparison of gallbladder cancer incidence rates between Japanese in Japan and those in the USA, we abstracted the age-standardized incidence rates (ASRs) from the Cancer Incidence in Five Continents Vol. I–X (CI5). International Agency for Research on Cancer provides the CI5 databases on the incidence of cancer recorded by cancer registries (regional and national) worldwide. We used ASRs for Japanese from the following cancer registries: Miyagi, Nagasaki and Osaka in Japan, and California–Los Angeles, California–San Francisco and Hawaii in the USA from the CI5 database. Furthermore, we referred the ASRs in the USA (SEER 9 registries and Hawaii). Years at cancer diagnosis were from 1959 to 2007 in Volume I–X in CI5; however, the years were a little different from registries.\nFigure \n1 shows the ASRs for gallbladder cancers coded as C23−24 (ICD10) for males. The ASRs in three Japanese registries tended to be higher than those for White and Black in US registries. The ASRs for Japanese in US registries were intermediate between those. The ASRs in Japan showed a peak around Vol. 8 (mid-1990s), and a decreasing trend thereafter, while the ASRs in the USA showed a slow decreasing trend during the observation period. \nFigure 2 shows the ASRs for gallbladder cancers for females. The overall pattern was similar to that observed for males. The ASRs for Japanese in US registries were close to those for White and Black in US registries. The peak in the ASR in Japan was slightly earlier than that observed in males, and one registry (Nagasaki) did not show a clear peak.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidence Rate For Gallbladder Cancer In Japanese In Japan And In The United States From The Cancer Incidence In Five Continents In order to make a comparison of gallbladder cancer incidence rates between Japanese in Japan and those in the USA, we abstracted the age-standardized incidence rates (ASRs) from the Cancer Incidence in Five Continents Vol. I–X (CI5). International Agency for Research on Cancer provides the CI5 databases on the incidence of cancer recorded by cancer registries (regional and national) worldwide. We used ASRs for Japanese from the following cancer registries: Miyagi, Nagasaki and Osaka in Japan, and California–Los Angeles, California–San Francisco and Hawaii in the USA from the CI5 database. Furthermore, we referred the ASRs in the USA (SEER 9 registries and Hawaii). Years at cancer diagnosis were from 1959 to 2007 in Volume I–X in CI5; however, the years were a little different from registries.\nFigure \n1 shows the ASRs for gallbladder cancers coded as C23−24 (ICD10) for males. The ASRs in three Japanese registries tended to be higher than those for White and Black in US registries. The ASRs for Japanese in US registries were intermediate between those. The ASRs in Japan showed a peak around Vol. 8 (mid-1990s), and a decreasing trend thereafter, while the ASRs in the USA showed a slow decreasing trend during the observation period. \nFigure 2 shows the ASRs for gallbladder cancers for females. The overall pattern was similar to that observed for males. The ASRs for Japanese in US registries were close to those for White and Black in US registries. The peak in the ASR in Japan was slightly earlier than that observed in males, and one registry (Nagasaki) did not show a clear peak. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"quantitative assessment cell surface proteome identify novel therapeutic targets cholangiocarcinoma background cholangiocarcinoma high mortality morbidity median survival less 6 months surgical resection appropriate certain circumstances distal cholangiocarcinoma difficult distinguish pancreatic cancers patients might receive optimum therapy proteomics study complex cellular proteins using mass spectrometry aim study determine constituent proteins cell surface model cholangiocarcinoma methods sample preparation technique enrich cell surface proteins intrahepatic cholangiocarcinoma cell line cc sw 1 developed modifying neutravidin biotin system isolation trypsin digestion purification peptides fractionated tandem mass spectrometry analysed ncbinr database mascot search algorithm results confirmed immunohistochemistry using peroxidase detection technique paraffin embedded sections resected specimens findings peptide enrichment confirmed electrophoresis 862 proteins consistently expressed samples n 3 271 proteins attributed cell surface included proteins used clinically staging disease cytokeratin 19 ck19 identifying cancer stem cells epithelial cell adhesion molecule epcam neural cell adhesion molecule ncam epithelial growth factor receptor egfr indicating potential differentiation frozzled receptor notch pathway novel markers tumour necrosis factor tnf receptor superfamily also identified immunohistochemistry confirmed findings interpretation results surface proteomic profiling help identify novel therapeutic targets cholangiocarcinoma development technique translated distinguish distal cholangiocarcinoma pancreatic cancers funding uk medical research council stn","probabilities":0.9467213,"Title":"Quantitative Assessment Of The Cell Surface Proteome To Identify Novel Therapeutic Targets In Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinoma has a high mortality and morbidity. Median survival is less than 6 months. Surgical resection is appropriate in certain circumstances. Because distal cholangiocarcinoma is difficult to distinguish from pancreatic cancers, patients might not receive optimum therapy. Proteomics is the study of complex cellular proteins using mass spectrometry. The aim of this study was to determine the constituent proteins on the cell surface of a model of cholangiocarcinoma. \r\n\r\n Methods: A sample preparation technique to enrich for cell surface proteins of the intrahepatic cholangiocarcinoma cell line CC-SW-1 was developed by modifying a NeutrAvidin-biotin system. After isolation, trypsin digestion, and purification, peptides were fractionated for tandem mass spectrometry before being analysed with the NCBInr database and the Mascot search algorithm. Results were confirmed by immunohistochemistry using a peroxidase detection technique on paraffin-embedded sections from resected specimens. \r\n\r\n Findings: Peptide enrichment was confirmed by electrophoresis. 862 proteins were consistently expressed between samples (n=3). 271 of these proteins were attributed only to the cell surface. They included proteins used clinically for staging disease (cytokeratin 19 [CK19]), identifying cancer stem cells (epithelial cell adhesion molecule [EpCAM], neural cell adhesion molecule [NCAM], epithelial growth factor receptor [EGFR]), and indicating potential for differentiation (Frozzled receptor, Notch pathway). Novel markers from the tumour necrosis factor (TNF) receptor superfamily were also identified. Immunohistochemistry confirmed these findings. \r\n\r\n Interpretation: The results from this surface proteomic profiling could help to identify novel therapeutic targets in cholangiocarcinoma. Further development of this technique could be translated to distinguish between distal cholangiocarcinoma and pancreatic cancers. \r\n\r\n Funding: UK Medical Research Council.","Source":"STN","category":"ANIMAL","training_data":"Quantitative Assessment Of The Cell Surface Proteome To Identify Novel Therapeutic Targets In Cholangiocarcinoma Background: Cholangiocarcinoma has a high mortality and morbidity. Median survival is less than 6 months. Surgical resection is appropriate in certain circumstances. Because distal cholangiocarcinoma is difficult to distinguish from pancreatic cancers, patients might not receive optimum therapy. Proteomics is the study of complex cellular proteins using mass spectrometry. The aim of this study was to determine the constituent proteins on the cell surface of a model of cholangiocarcinoma. \r\n\r\n Methods: A sample preparation technique to enrich for cell surface proteins of the intrahepatic cholangiocarcinoma cell line CC-SW-1 was developed by modifying a NeutrAvidin-biotin system. After isolation, trypsin digestion, and purification, peptides were fractionated for tandem mass spectrometry before being analysed with the NCBInr database and the Mascot search algorithm. Results were confirmed by immunohistochemistry using a peroxidase detection technique on paraffin-embedded sections from resected specimens. \r\n\r\n Findings: Peptide enrichment was confirmed by electrophoresis. 862 proteins were consistently expressed between samples (n=3). 271 of these proteins were attributed only to the cell surface. They included proteins used clinically for staging disease (cytokeratin 19 [CK19]), identifying cancer stem cells (epithelial cell adhesion molecule [EpCAM], neural cell adhesion molecule [NCAM], epithelial growth factor receptor [EGFR]), and indicating potential for differentiation (Frozzled receptor, Notch pathway). Novel markers from the tumour necrosis factor (TNF) receptor superfamily were also identified. Immunohistochemistry confirmed these findings. \r\n\r\n Interpretation: The results from this surface proteomic profiling could help to identify novel therapeutic targets in cholangiocarcinoma. Further development of this technique could be translated to distinguish between distal cholangiocarcinoma and pancreatic cancers. \r\n\r\n Funding: UK Medical Research Council. STN","prediction_labels":"ANIMAL"},{"cleaned":"long term outcome surgical resection intraductal papillary neoplasm bile duct background aims intraductal papillary neoplasm bile duct ipnb specific type bile duct tumor studies surgical outcomes ipnb therefore investigated survival patients underwent curative surgical resection ipnb methods retrospectively reviewed medical pathological records 148 ipnb patients underwent curative intent hepatic resection january 2005 december 2011 examine prognosis ipnb demographic operative parameters analyzed effect survival patients results median survival ipnb patients 1326 days respective 1 3 5 year overall survival 83 6 95 ci 76 5 88 7 64 4 95 ci 56 0 71 6 47 95 ci 38 4 55 7 level invasiveness ipnb predicted survival well malignant ipnb univariate analysis showed serum ca19 9 level lymph node metastasis completeness resection significant prognostic factors lymph node metastasis completeness resection found multivariate analysis significantly related survival patients conclusions level invasiveness lymph node status found associated patient survival adequacy surgery recommend r0 resection attempted patients ipnb pubmed","probabilities":0.9799733,"Title":"Long-term outcome of surgical resection for intraductal papillary neoplasm of the bile duct","Abstract":"BACKGROUND AND AIMS: Intraductal papillary neoplasm of the bile duct (IPNB) is a specific type of bile duct tumor. Studies about the surgical outcomes for IPNB are few; therefore, we investigated the survival of patients who underwent curative surgical resection of IPNB. METHODS: We retrospectively reviewed the medical and pathological records of 148 IPNB patients who underwent curative-intent hepatic resection between January 2005 and December 2011, to examine the prognosis of IPNB. All demographic and operative parameters were analyzed the effect on survival of patients. RESULTS: The median survival of IPNB patients was 1326 days with a respective 1, 3, and 5 year overall survival of 83.6% (95%CI: 76.5-88.7), 64.4% (95%CI: 56.0-71.6), and 47% (95%CI: 38.4-55.7). The level of invasiveness of IPNB predicted survival very well. For malignant IPNB, univariate analysis showed that serum CA19-9 level, lymph node metastasis, and completeness of resection were significant prognostic factors. Lymph node metastasis and completeness of resection were found in multivariate analysis to be significantly related to survival of the patients. CONCLUSIONS: The level of invasiveness and lymph node status were found to be associated with patient survival, as was adequacy of surgery. We recommend R0 resection be attempted for patients with IPNB.","Source":"PubMed","category":"HUMAN","training_data":"Long-term outcome of surgical resection for intraductal papillary neoplasm of the bile duct BACKGROUND AND AIMS: Intraductal papillary neoplasm of the bile duct (IPNB) is a specific type of bile duct tumor. Studies about the surgical outcomes for IPNB are few; therefore, we investigated the survival of patients who underwent curative surgical resection of IPNB. METHODS: We retrospectively reviewed the medical and pathological records of 148 IPNB patients who underwent curative-intent hepatic resection between January 2005 and December 2011, to examine the prognosis of IPNB. All demographic and operative parameters were analyzed the effect on survival of patients. RESULTS: The median survival of IPNB patients was 1326 days with a respective 1, 3, and 5 year overall survival of 83.6% (95%CI: 76.5-88.7), 64.4% (95%CI: 56.0-71.6), and 47% (95%CI: 38.4-55.7). The level of invasiveness of IPNB predicted survival very well. For malignant IPNB, univariate analysis showed that serum CA19-9 level, lymph node metastasis, and completeness of resection were significant prognostic factors. Lymph node metastasis and completeness of resection were found in multivariate analysis to be significantly related to survival of the patients. CONCLUSIONS: The level of invasiveness and lymph node status were found to be associated with patient survival, as was adequacy of surgery. We recommend R0 resection be attempted for patients with IPNB. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical outcomes toxicity proton beam therapy advanced cholangiocarcinoma background examined efficacy toxicity proton beam therapy pbt treating advanced cholangiocarcinoma methods clinical data outcomes 28 cholangiocarcinoma patients treated pbt january 2009 august 2011 retrospectively examined kaplan meier method used estimate overall survival os progression free survival pfs local control lc rates log rank test analyze effects different clinical treatment variables survival acute late toxicities assessed using national cancer institute common terminology criteria adverse events version 4 0 results median age 17 male 11 female patients 71 years range 41 84 years intrahepatic peripheral cholangiocarcinoma n 6 hilar cholangiocarcinoma klatskin tumor n 6 distal extrahepatic cholangiocarcinoma n 3 gallbladder cancer n 3 local lymph node recurrence n 10 size 20 175 mm median 52 mm median radiation dose 68 2 gy relative biological effectiveness rbe range 50 6 80 gy rbe delivery fractions 2 0 3 2 gy rbe daily median follow duration 12 months range 3 29 months fifteen patients underwent chemotherapy 8 patients palliative biliary stent placement prior pbt os pfs lc rates 1 year 49 0 29 5 67 7 respectively lc achieved 6 patients better patients administered biologically equivalent dose 10 bed10 70 gy compared administered 70 gy 83 1 vs 22 2 respectively 1 year variables tumor size performance status associated survival late gastrointestinal toxicities grade 2 greater observed 7 patients 12 months pbt cholangitis observed 11 patients 3 patients required stent replacement conclusions relatively high lc rates pbt advanced cholangiocarcinoma achieved delivery bed10 70 gy gastrointestinal toxicities especially duodenum dose limiting toxicities associated pbt early metastatic progression remains treatment obstacle pubmed","probabilities":0.9799733,"Title":"Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma","Abstract":"BACKGROUND: We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma. METHODS: The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20-175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered < 70 Gy (83.1% vs. 22.2%, respectively, at 1 year). The variables of tumor size and performance status were associated with survival. Late gastrointestinal toxicities grade 2 or greater were observed in 7 patients <12 months after PBT. Cholangitis was observed in 11 patients and 3 patients required stent replacement. CONCLUSIONS: Relatively high LC rates after PBT for advanced cholangiocarcinoma can be achieved by delivery of a BED10 > 70 Gy. Gastrointestinal toxicities, especially those of the duodenum, are dose-limiting toxicities associated with PBT, and early metastatic progression remains a treatment obstacle.","Source":"PubMed","category":"HUMAN","training_data":"Clinical outcomes and toxicity of proton beam therapy for advanced cholangiocarcinoma BACKGROUND: We examined the efficacy and toxicity of proton beam therapy (PBT) for treating advanced cholangiocarcinoma. METHODS: The clinical data and outcomes of 28 cholangiocarcinoma patients treated with PBT between January 2009 and August 2011 were retrospectively examined. The Kaplan-Meier method was used to estimate overall survival (OS), progression-free survival (PFS), and local control (LC) rates, and the log-rank test to analyze the effects of different clinical and treatment variables on survival. Acute and late toxicities were assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. RESULTS: The median age of the 17 male and 11 female patients was 71 years (range, 41 to 84 years; intrahepatic/peripheral cholangiocarcinoma, n = 6; hilar cholangiocarcinoma/Klatskin tumor, n = 6; distal extrahepatic cholangiocarcinoma, n = 3; gallbladder cancer, n = 3; local or lymph node recurrence, n = 10; size, 20-175 mm; median 52 mm). The median radiation dose was 68.2 Gy (relative biological effectiveness [RBE]) (range, 50.6 to 80 Gy (RBE)), with delivery of fractions of 2.0 to 3.2 Gy (RBE) daily. The median follow-up duration was 12 months (range, 3 to 29 months). Fifteen patients underwent chemotherapy and 8 patients, palliative biliary stent placement prior to PBT. OS, PFS, and LC rates at 1 year were 49.0%, 29.5%, and 67.7%, respectively. LC was achieved in 6 patients, and was better in patients administered a biologically equivalent dose of 10 (BED10) > 70 Gy compared to those administered < 70 Gy (83.1% vs. 22.2%, respectively, at 1 year). The variables of tumor size and performance status were associated with survival. Late gastrointestinal toxicities grade 2 or greater were observed in 7 patients <12 months after PBT. Cholangitis was observed in 11 patients and 3 patients required stent replacement. CONCLUSIONS: Relatively high LC rates after PBT for advanced cholangiocarcinoma can be achieved by delivery of a BED10 > 70 Gy. Gastrointestinal toxicities, especially those of the duodenum, are dose-limiting toxicities associated with PBT, and early metastatic progression remains a treatment obstacle. PubMed","prediction_labels":"HUMAN"},{"cleaned":"biliary tract cancer patient derived xenografts surgeon impact individualized medicine background aims biliary tract tumors uncommon highly aggressive malignancies poor survival outcomes due low incidence research effective therapeutics limited novel research platforms pre clinical studies desperately needed sought develop patient derived biliary tract cancer xenograft catalog methods appropriate consent approval surplus malignant tissues obtained surgical resection radiographic biopsy implanted immunocompromised mice mice monitored xenograft growth established xenografts verified hepatobiliary pathologist xenograft characteristics correlated original patient tumor characteristics oncologic outcomes subset xenografts genomically characterized using mate pair sequencing mpseq results october 2013 january 2018 87 patients histologically confirmed biliary tract carcinomas enrolled 87 patients 47 validated pdx models successfully generated majority pdx models created surgical resection specimens n 44 94 likely successfully engraft compared radiologic biopsies p 0 03 histologic recapitulation original patient tumor morphology observed xenografts successful engraftment independent predictor worse recurrence free survival mpseq showed genetically diverse tumors frequent alterations cdkn2a smad4 nrg1 tp53 sequencing also identified worse survival patients tumors containing tetraploid genomes conclusions largest series biliary tract cancer xenografts reported date histologic genomic analysis patient derived xenografts demonstrates accurate recapitulation original tumor morphology direct correlations patient outcomes successful development biliary cancer tumografts feasible may used direct subsequent therapy high recurrence risk patients lay summary patient biliary tract tumors grown immunocompromised mice invaluable resource treatment biliary tract cancers used guide individualized cancer treatment high risk patients stn","probabilities":0.7777778,"Title":"Biliary Tract Cancer Patient-Derived Xenografts: Surgeon Impact On Individualized Medicine","Abstract":"Background & aims: Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Due to their low incidence, research into effective therapeutics has been limited. Novel research platforms for pre-clinical studies are desperately needed. We sought to develop a patient-derived biliary tract cancer xenograft catalog. \r\n\r\n Methods: With appropriate consent and approval, surplus malignant tissues were obtained from surgical resection or radiographic biopsy and implanted into immunocompromised mice. Mice were monitored for xenograft growth. Established xenografts were verified by a hepatobiliary pathologist. Xenograft characteristics were correlated with original patient/tumor characteristics and oncologic outcomes. A subset of xenografts were then genomically characterized using Mate Pair sequencing (MPseq). \r\n\r\n Results: Between October 2013 and January 2018, 87 patients with histologically confirmed biliary tract carcinomas were enrolled. Of the 87 patients, 47 validated PDX models were successfully generated. The majority of the PDX models were created from surgical resection specimens (n = 44, 94%), which were more likely to successfully engraft when compared to radiologic biopsies (p = 0.03). Histologic recapitulation of original patient tumor morphology was observed in all xenografts. Successful engraftment was an independent predictor for worse recurrence-free survival. MPseq showed genetically diverse tumors with frequent alterations of CDKN2A, SMAD4, NRG1, TP53. Sequencing also identified worse survival in patients with tumors containing tetraploid genomes. \r\n\r\n Conclusions: This is the largest series of biliary tract cancer xenografts reported to date. Histologic and genomic analysis of patient-derived xenografts demonstrates accurate recapitulation of original tumor morphology with direct correlations to patient outcomes. Successful development of biliary cancer tumografts is feasible and may be used to direct subsequent therapy in high recurrence risk patients. \r\n\r\n Lay summary: Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients.","Source":"STN","category":"ANIMAL","training_data":"Biliary Tract Cancer Patient-Derived Xenografts: Surgeon Impact On Individualized Medicine Background & aims: Biliary tract tumors are uncommon but highly aggressive malignancies with poor survival outcomes. Due to their low incidence, research into effective therapeutics has been limited. Novel research platforms for pre-clinical studies are desperately needed. We sought to develop a patient-derived biliary tract cancer xenograft catalog. \r\n\r\n Methods: With appropriate consent and approval, surplus malignant tissues were obtained from surgical resection or radiographic biopsy and implanted into immunocompromised mice. Mice were monitored for xenograft growth. Established xenografts were verified by a hepatobiliary pathologist. Xenograft characteristics were correlated with original patient/tumor characteristics and oncologic outcomes. A subset of xenografts were then genomically characterized using Mate Pair sequencing (MPseq). \r\n\r\n Results: Between October 2013 and January 2018, 87 patients with histologically confirmed biliary tract carcinomas were enrolled. Of the 87 patients, 47 validated PDX models were successfully generated. The majority of the PDX models were created from surgical resection specimens (n = 44, 94%), which were more likely to successfully engraft when compared to radiologic biopsies (p = 0.03). Histologic recapitulation of original patient tumor morphology was observed in all xenografts. Successful engraftment was an independent predictor for worse recurrence-free survival. MPseq showed genetically diverse tumors with frequent alterations of CDKN2A, SMAD4, NRG1, TP53. Sequencing also identified worse survival in patients with tumors containing tetraploid genomes. \r\n\r\n Conclusions: This is the largest series of biliary tract cancer xenografts reported to date. Histologic and genomic analysis of patient-derived xenografts demonstrates accurate recapitulation of original tumor morphology with direct correlations to patient outcomes. Successful development of biliary cancer tumografts is feasible and may be used to direct subsequent therapy in high recurrence risk patients. \r\n\r\n Lay summary: Patient biliary tract tumors grown in immunocompromised mice are an invaluable resource in the treatment of biliary tract cancers. They can be used to guide individualized cancer treatment in high-risk patients. STN","prediction_labels":"ANIMAL"},{"cleaned":"locoregional recurrence curative intent resection intrahepatic cholangiocarcinoma implications adjuvant radiotherapy backgrounds intrahepatic cholangiocarcinoma frequent site failure curative intent resection liver identified risk factors locoregional recurrence curative intent resection intrahepatic cholangiocarcinoma methods medical records 115 patients treated surgical resection alone intrahepatic cholangiocarcinoma november 2000 december 2010 retrospectively reviewed locoregional failure defined recurrence within 20 mm resection margin regional lymph node overall survival locoregional recurrence rates analyzed using kaplan meier methods prognostic factors analyzed using cox proportional hazards model results median follow duration surviving patients 61 months range 8 139 sixty six patients recurrence 45 66 patients 68 locoregional recurrence 5 year overall survival locoregional control rates 49 1 51 6 respectively t2b disease r1 resection associated locoregional recurrence multivariate analysis patients divided two groups whether risk factors exist 5 year locoregional control rates low risk factor n 64 high 1 2 risk factors n 51 risk groups 62 5 34 7 respectively p 0 001 conclusions curative intent resection locoregional control survival patients intrahepatic cholangiocarcinoma far satisfactory studies needed evaluate potential benefit adjuvant locoregional treatment radiotherapy patients high risk factors t2b disease r1 resection pubmed","probabilities":0.9799733,"Title":"Locoregional recurrence after curative intent resection for intrahepatic cholangiocarcinoma: implications for adjuvant radiotherapy","Abstract":"BACKGROUNDS: As for intrahepatic cholangiocarcinoma, the most frequent site of failure after curative intent resection is the liver. We identified the risk factors for locoregional recurrence after curative intent resection for intrahepatic cholangiocarcinoma. METHODS: Medical records of 115 patients treated with surgical resection alone for intrahepatic cholangiocarcinoma from November 2000 to December 2010 were retrospectively reviewed. Locoregional failure was defined as recurrence within 20 mm from resection margin or regional lymph node. Overall survival and locoregional recurrence rates were analyzed using Kaplan-Meier methods, and the prognostic factors were analyzed using Cox proportional hazards model. RESULTS: Median follow-up duration of surviving patients was 61 months (range 8-139). Sixty-six patients had recurrence, and 45 of 66 patients (68 %) had locoregional recurrence. The 5-year overall survival and locoregional control rates were 49.1 and 51.6 %, respectively. ≥ T2b disease and R1 resection were associated with locoregional recurrence in multivariate analysis. Patients were divided into two groups whether these risk factors exist or not. The 5-year locoregional control rates of low (no risk factor n = 64) and high (1 or 2 risk factors n = 51) risk groups were 62.5 and 34.7 %, respectively (P = 0.001). CONCLUSIONS: After curative intent resection, locoregional control and survival of patients with intrahepatic cholangiocarcinoma were far from satisfactory. Further studies are needed to evaluate the potential benefit of adjuvant locoregional treatment such as radiotherapy for patients with high-risk factors (≥ T2b disease or R1 resection).","Source":"PubMed","category":"HUMAN","training_data":"Locoregional recurrence after curative intent resection for intrahepatic cholangiocarcinoma: implications for adjuvant radiotherapy BACKGROUNDS: As for intrahepatic cholangiocarcinoma, the most frequent site of failure after curative intent resection is the liver. We identified the risk factors for locoregional recurrence after curative intent resection for intrahepatic cholangiocarcinoma. METHODS: Medical records of 115 patients treated with surgical resection alone for intrahepatic cholangiocarcinoma from November 2000 to December 2010 were retrospectively reviewed. Locoregional failure was defined as recurrence within 20 mm from resection margin or regional lymph node. Overall survival and locoregional recurrence rates were analyzed using Kaplan-Meier methods, and the prognostic factors were analyzed using Cox proportional hazards model. RESULTS: Median follow-up duration of surviving patients was 61 months (range 8-139). Sixty-six patients had recurrence, and 45 of 66 patients (68 %) had locoregional recurrence. The 5-year overall survival and locoregional control rates were 49.1 and 51.6 %, respectively. ≥ T2b disease and R1 resection were associated with locoregional recurrence in multivariate analysis. Patients were divided into two groups whether these risk factors exist or not. The 5-year locoregional control rates of low (no risk factor n = 64) and high (1 or 2 risk factors n = 51) risk groups were 62.5 and 34.7 %, respectively (P = 0.001). CONCLUSIONS: After curative intent resection, locoregional control and survival of patients with intrahepatic cholangiocarcinoma were far from satisfactory. Further studies are needed to evaluate the potential benefit of adjuvant locoregional treatment such as radiotherapy for patients with high-risk factors (≥ T2b disease or R1 resection). PubMed","prediction_labels":"HUMAN"},{"cleaned":"role ap 2a mapk7 regulation autocrine tgf mir 200b signals maintain epithelial mesenchymal transition cholangiocarcinoma background cholangiocarcinoma cca characterized early lymphatic metastasis low survival rate epithelial mesenchymal transition emt able induce tumor metastasis although tgf mir 200 signals promote emt various types cancer regulatory mechanism cca still unclear methods expression mir 200b tgf emt markers measured tumor samples cell lines qrt pcr western blot cck8 assay performed measure cell viability transwell assay used evaluate migration invasion target genes mir 200b transcription factor tgf analyzed using dual luciferase reporter system results demonstrated cca exhibited remarkable emt phenotype mir 200b reduced cca patients n 20 negatively correlated tgf moreover two cca cells hccc rbe epithelial appearances treated tgf showed fibroblastic like cell morphology downregulated mir 200b expression forced expression mir 200b abrogated tgf induced emt initiation decreased cell proliferation migration invasion vitro also tfap2a encode ap 2 mapk7 found targeted mir 200b downregulate emt ap 2 inhibited mir 200b directly promoting transcription tgfb1 overexpression mapk7 significantly reversed mir 200b induced inhibition emt migration proliferation increasing expression tgf cyclin d1 cdk2 administration mir 200b induced remarkably tumor regression vivo reduced effect tgf related emt ap 2 mapk7 dependent manner conclusions study highlights mir 200b based gene therapy effective treatment cca stn","probabilities":0.9467213,"Title":"Role Of Ap-2A And Mapk7 In The Regulation Of Autocrine Tgf-ß/Mir-200B Signals To Maintain Epithelial-Mesenchymal Transition In Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinoma (CCA) is characterized by early lymphatic, metastasis, and low survival rate. Epithelial-mesenchymal transition (EMT) is able to induce tumor metastasis. Although the TGF-β/miR-200 signals promote EMT in various types of cancer, the regulatory mechanism in CCA is still unclear. \r\n\r\n Methods: Expression of miR-200b, TGF-β, and EMT markers were measured in tumor samples and cell lines by qRT-PCR and western blot. CCK8 assay was performed to measure the cell viability. Transwell assay was used to evaluate migration and invasion. The target genes of miR-200b and transcription factor of TGF-β were analyzed using dual-luciferase reporter system. \r\n\r\n Results: We have demonstrated that CCA exhibited remarkable EMT phenotype and miR-200b was reduced in CCA patients (n = 20) and negatively correlated to TGF-β. Moreover, two CCA cells, HCCC, and RBE, with epithelial appearances treated with TGF-β, showed fibroblastic-like cell morphology with downregulated miR-200b expression. Forced expression of miR-200b abrogated TGF-β-induced EMT initiation, with decreased cell proliferation, migration, and invasion in vitro. Also, TFAP2A (encode AP-2α) and MAPK7 were found to be targeted by miR-200b to downregulate EMT and AP-2α inhibited miR-200b by directly promoting transcription of TGFB1. Overexpression of MAPK7 significantly reversed miR-200b-induced inhibition of EMT, migration, and proliferation by increasing the expression of TGF-β, cyclin D1, and Cdk2. Further, the administration of miR-200b induced a remarkably tumor regression in vivo and reduced the effect of TGF-β-related EMT in AP-2α and MAPK7-dependent manner. \r\n\r\n Conclusions: Our study highlights that miR-200b-based gene therapy is effective in the treatment of CCA.","Source":"STN","category":"ANIMAL","training_data":"Role Of Ap-2A And Mapk7 In The Regulation Of Autocrine Tgf-ß/Mir-200B Signals To Maintain Epithelial-Mesenchymal Transition In Cholangiocarcinoma Background: Cholangiocarcinoma (CCA) is characterized by early lymphatic, metastasis, and low survival rate. Epithelial-mesenchymal transition (EMT) is able to induce tumor metastasis. Although the TGF-β/miR-200 signals promote EMT in various types of cancer, the regulatory mechanism in CCA is still unclear. \r\n\r\n Methods: Expression of miR-200b, TGF-β, and EMT markers were measured in tumor samples and cell lines by qRT-PCR and western blot. CCK8 assay was performed to measure the cell viability. Transwell assay was used to evaluate migration and invasion. The target genes of miR-200b and transcription factor of TGF-β were analyzed using dual-luciferase reporter system. \r\n\r\n Results: We have demonstrated that CCA exhibited remarkable EMT phenotype and miR-200b was reduced in CCA patients (n = 20) and negatively correlated to TGF-β. Moreover, two CCA cells, HCCC, and RBE, with epithelial appearances treated with TGF-β, showed fibroblastic-like cell morphology with downregulated miR-200b expression. Forced expression of miR-200b abrogated TGF-β-induced EMT initiation, with decreased cell proliferation, migration, and invasion in vitro. Also, TFAP2A (encode AP-2α) and MAPK7 were found to be targeted by miR-200b to downregulate EMT and AP-2α inhibited miR-200b by directly promoting transcription of TGFB1. Overexpression of MAPK7 significantly reversed miR-200b-induced inhibition of EMT, migration, and proliferation by increasing the expression of TGF-β, cyclin D1, and Cdk2. Further, the administration of miR-200b induced a remarkably tumor regression in vivo and reduced the effect of TGF-β-related EMT in AP-2α and MAPK7-dependent manner. \r\n\r\n Conclusions: Our study highlights that miR-200b-based gene therapy is effective in the treatment of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognosis curative resection gallbladder cancer hilar invasion similar hilar cholangiocarcinoma background purpose gallbladder cancer gbc often invades hepatic hilum even small tumors cause obstructive jaundice operative intervention gbc obstructive jaundice sometimes recommended associated poor prognosis however extended procedure recommended patients hilar cholangiocarcinoma hc therefore compared postoperative survival patients gbc invading hepatic hilum hc methods 1998 2008 27 patients gbc invasion hepatic hilum hgbc 124 hc underwent surgical resection curative intent department surgical oncology hokkaido university graduate school medicine study included patients gbc without peritoneal dissemination liver para aortic lymph node metastasis extended right hemihepatectomy extrahepatic bile duct resection comprise treatment choice gbc hilar invasion hgbc aimed achieve r0 outcomes aggressive vascular resection concomitant resection directly invaded organs around gbc along extended right hemihepatectomy results analyzed 27 patients hgbc age 58 83 years median 71 years male female 13 14 124 hc age 45 80 years median 69 years male female 94 30 3 5 year survival rates 43 24 hgbc 58 38 hc respectively differ significantly p 0 14 preoperative obstructive jaundice complication 22 81 95 77 patients hgbc hc respectively 5 year survival rates 40 36 respectively differ significantly p 0 61 5 year survival rates extended right hemihepatectomy resect tumor curative intent 34 34 hgbc hc differ significantly p 0 14 conclusions prognosis curative resection gbc hilar invasion similar hc selected patients aggressive surgery advanced gbc hilar invasion might increase survival rates pubmed","probabilities":0.9799733,"Title":"The prognosis after curative resection of gallbladder cancer with hilar invasion is similar to that of hilar cholangiocarcinoma","Abstract":"BACKGROUND/PURPOSE: Gallbladder cancer (GBC) often invades the hepatic hilum and even small tumors can cause obstructive jaundice. Operative intervention for GBC with obstructive jaundice is sometimes not recommended because it is associated with a poor prognosis. However, the extended procedure is recommended for patients with hilar cholangiocarcinoma (HC). We therefore compared the postoperative survival of patients with GBC invading the hepatic hilum with that with HC. METHODS: Between 1998 and 2008, 27 patients with GBC invasion of the hepatic hilum (hGBC) and 124 with HC underwent surgical resection with curative intent in the Department of Surgical Oncology, Hokkaido University Graduate School of Medicine. This study included patients with GBC without peritoneal dissemination and liver or para-aortic lymph node metastasis. Extended right hemihepatectomy and extrahepatic bile duct resection comprise the treatment of choice for GBC with hilar invasion (hGBC). We aimed to achieve R0 outcomes by aggressive vascular resection and/or concomitant resection of directly invaded organs around the GBC along with extended right hemihepatectomy. RESULTS: We analyzed 27 patients with hGBC (age 58-83 years; median 71 years; male:female 13:14) and 124 with HC (age 45-80 years; median 69 years; male:female 94:30). The 3- and 5-year survival rates of 43 and 24% for hGBC and 58 and 38% for HC, respectively, did not differ significantly (p = 0.14). Preoperative obstructive jaundice was a complication in 22 (81%) and 95 (77%) patients with hGBC and HC, respectively. The 5-year survival rates were 40 and 36%, respectively, which did not differ significantly (p = 0.61). The 5-year survival rates after extended right hemihepatectomy to resect the tumor with curative intent were 34 and 34% for hGBC and HC, which did not differ significantly (p = 0.14). CONCLUSIONS: The prognosis after curative resection of GBC with hilar invasion is similar to that of HC in selected patients. Aggressive surgery for advanced GBC with hilar invasion might increase survival rates.","Source":"PubMed","category":"HUMAN","training_data":"The prognosis after curative resection of gallbladder cancer with hilar invasion is similar to that of hilar cholangiocarcinoma BACKGROUND/PURPOSE: Gallbladder cancer (GBC) often invades the hepatic hilum and even small tumors can cause obstructive jaundice. Operative intervention for GBC with obstructive jaundice is sometimes not recommended because it is associated with a poor prognosis. However, the extended procedure is recommended for patients with hilar cholangiocarcinoma (HC). We therefore compared the postoperative survival of patients with GBC invading the hepatic hilum with that with HC. METHODS: Between 1998 and 2008, 27 patients with GBC invasion of the hepatic hilum (hGBC) and 124 with HC underwent surgical resection with curative intent in the Department of Surgical Oncology, Hokkaido University Graduate School of Medicine. This study included patients with GBC without peritoneal dissemination and liver or para-aortic lymph node metastasis. Extended right hemihepatectomy and extrahepatic bile duct resection comprise the treatment of choice for GBC with hilar invasion (hGBC). We aimed to achieve R0 outcomes by aggressive vascular resection and/or concomitant resection of directly invaded organs around the GBC along with extended right hemihepatectomy. RESULTS: We analyzed 27 patients with hGBC (age 58-83 years; median 71 years; male:female 13:14) and 124 with HC (age 45-80 years; median 69 years; male:female 94:30). The 3- and 5-year survival rates of 43 and 24% for hGBC and 58 and 38% for HC, respectively, did not differ significantly (p = 0.14). Preoperative obstructive jaundice was a complication in 22 (81%) and 95 (77%) patients with hGBC and HC, respectively. The 5-year survival rates were 40 and 36%, respectively, which did not differ significantly (p = 0.61). The 5-year survival rates after extended right hemihepatectomy to resect the tumor with curative intent were 34 and 34% for hGBC and HC, which did not differ significantly (p = 0.14). CONCLUSIONS: The prognosis after curative resection of GBC with hilar invasion is similar to that of HC in selected patients. Aggressive surgery for advanced GBC with hilar invasion might increase survival rates. PubMed","prediction_labels":"HUMAN"},{"cleaned":"increasing mortality united states cholangiocarcinoma analysis national center health statistics database background mortality united states decreased cancers mortality combined hepatocellular liver cancer intrahepatic cholangiocarcinoma icc increased ranked 1st annual percent increase among cancer sites reported statistics combine icc liver cancers mortality rates cholangiocarcinoma cca remain unknown study determine cca mortality trends variation based national data methods nation wide study based underlying cause death data collected national center health statistics nchs 1999 2014 center disease control cdc wide ranging online data epidemiologic research wonder system used obtain data icc extra hepatic cca ecc defined icd 10 diagnosis codes age adjusted mortality rate standardized us population 2000 results 7000 cca deaths year us 2013 cca mortality aged 25 increased 36 1999 2014 2 2 per 100 000 95 confidence interval ci 2 1 2 3 3 0 per 100 000 95 ci 2 9 3 1 mortality rates lower among females compared males risk ratio rr 0 78 95 ci 0 77 0 79 asians highest mortality 2004 2014 increase cca mortality highest among african americans 45 followed asians 22 whites 20 conclusion based recent national data cca mortality rates increased substantially past decade among different race ethnic groups african americans highest increase cca mortality stn","probabilities":0.9799733,"Title":"Increasing Mortality In The United States From Cholangiocarcinoma: An Analysis Of The National Center For Health Statistics Database","Abstract":"Background: While mortality in the United States has decreased for most cancers, mortality from combined hepatocellular liver cancer and intrahepatic cholangiocarcinoma (ICC) has increased and ranked 1st in annual percent increase among cancer sites. Because reported statistics combine ICC with other liver cancers, mortality rates of cholangiocarcinoma (CCA) remain unknown. This study is to determine CCA mortality trends and variation based on national data. \r\n\r\n Methods: This nation-wide study was based on the underlying cause of death data collected by the National Center for Health Statistics (NCHS) between 1999 and 2014. The Center for Disease Control (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) system was used to obtain data. ICC and extra-hepatic CCA (ECC) were defined by ICD-10 diagnosis codes. Age-adjusted mortality rate was standardized to the US population in 2000. \r\n\r\n Results: There were more than 7000 CCA deaths each year in the US after 2013. CCA mortality for those aged 25+ increased 36 % between 1999 and 2014, from 2.2 per 100,000 (95 % confidence interval [CI] 2.1-2.3) to 3.0 per 100,000 (95 % CI, 2.9-3.1). Mortality rates were lower among females compared with males (risk ratio [RR] 0.78, 95 % CI 0.77-0.79). Asians had the highest mortality. Between 2004 and 2014, the increase in CCA mortality was highest among African Americans (45 %) followed by Asians (22 %), and whites (20 %). \r\n\r\n Conclusion: Based on the most recent national data, CCA mortality rates have increased substantially in the past decade. Among different race/ethnic groups, African Americans have the highest increase in CCA mortality.","Source":"STN","category":"HUMAN","training_data":"Increasing Mortality In The United States From Cholangiocarcinoma: An Analysis Of The National Center For Health Statistics Database Background: While mortality in the United States has decreased for most cancers, mortality from combined hepatocellular liver cancer and intrahepatic cholangiocarcinoma (ICC) has increased and ranked 1st in annual percent increase among cancer sites. Because reported statistics combine ICC with other liver cancers, mortality rates of cholangiocarcinoma (CCA) remain unknown. This study is to determine CCA mortality trends and variation based on national data. \r\n\r\n Methods: This nation-wide study was based on the underlying cause of death data collected by the National Center for Health Statistics (NCHS) between 1999 and 2014. The Center for Disease Control (CDC) Wide-ranging Online Data for Epidemiologic Research (WONDER) system was used to obtain data. ICC and extra-hepatic CCA (ECC) were defined by ICD-10 diagnosis codes. Age-adjusted mortality rate was standardized to the US population in 2000. \r\n\r\n Results: There were more than 7000 CCA deaths each year in the US after 2013. CCA mortality for those aged 25+ increased 36 % between 1999 and 2014, from 2.2 per 100,000 (95 % confidence interval [CI] 2.1-2.3) to 3.0 per 100,000 (95 % CI, 2.9-3.1). Mortality rates were lower among females compared with males (risk ratio [RR] 0.78, 95 % CI 0.77-0.79). Asians had the highest mortality. Between 2004 and 2014, the increase in CCA mortality was highest among African Americans (45 %) followed by Asians (22 %), and whites (20 %). \r\n\r\n Conclusion: Based on the most recent national data, CCA mortality rates have increased substantially in the past decade. Among different race/ethnic groups, African Americans have the highest increase in CCA mortality. STN","prediction_labels":"HUMAN"},{"cleaned":"epidemiology risk factors cholangiocarcinoma background cholangiocarcinoma cca second common primary liver cancer characterized late diagnosis fatal outcome recent epidemiological reports indicate increasing worldwide incidence intrahepatic cca decreasing incidence extrahepatic cca methods review present overview incidence epidemiology cca possible strategies screening surveillance results efficient strategies screening surveillance cca established far vast majority cca occur sporadically without apparent cause however several risk factors liver flukes chronic biliary liver diseases lifestyle related aspects causing chronic inflammation cholestasis liver linked development cca risk factors likely contribute increased incidence observed countries also explain wide geographical differences incidence cca conclusion several risk factors cca identified given dismal prognosis advanced cca regular surveillance examinations combination ultrasonography laboratory tests appear useful patients risk need explored prospective trials google scholar","probabilities":0.9799733,"Title":"Epidemiology And Risk Factors Of Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinoma (CCA) is the second most common primary liver cancer, being characterized by its late diagnosis and fatal outcome. Recent epidemiological reports indicate an increasing worldwide incidence of intrahepatic CCA but a decreasing incidence of extrahepatic CCA. Methods: In this review, we present an overview of the incidence and epidemiology of CCA and possible strategies for screening and surveillance. Results: Efficient strategies for the screening and surveillance of CCA have not been established so far. The vast majority of CCA occur sporadically without any apparent cause; however, several risk factors such as liver flukes, chronic biliary and liver diseases, and lifestyle-related aspects causing chronic inflammation and cholestasis in the liver have been linked to the development of CCA. These risk factors likely contribute to the increased incidence observed in some countries and also explain the wide geographical differences in the incidence of CCA. Conclusion: Several risk factors for CCA have been identified. Given the dismal prognosis of advanced CCA, regular surveillance examinations with a combination of ultrasonography and laboratory tests appear to be useful in patients at risk and need to be explored in prospective trials.","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology And Risk Factors Of Cholangiocarcinoma Background: Cholangiocarcinoma (CCA) is the second most common primary liver cancer, being characterized by its late diagnosis and fatal outcome. Recent epidemiological reports indicate an increasing worldwide incidence of intrahepatic CCA but a decreasing incidence of extrahepatic CCA. Methods: In this review, we present an overview of the incidence and epidemiology of CCA and possible strategies for screening and surveillance. Results: Efficient strategies for the screening and surveillance of CCA have not been established so far. The vast majority of CCA occur sporadically without any apparent cause; however, several risk factors such as liver flukes, chronic biliary and liver diseases, and lifestyle-related aspects causing chronic inflammation and cholestasis in the liver have been linked to the development of CCA. These risk factors likely contribute to the increased incidence observed in some countries and also explain the wide geographical differences in the incidence of CCA. Conclusion: Several risk factors for CCA have been identified. Given the dismal prognosis of advanced CCA, regular surveillance examinations with a combination of ultrasonography and laboratory tests appear to be useful in patients at risk and need to be explored in prospective trials. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"serum cell free dna methylation opcml hoxd9 biomarker may aid differential diagnosis cholangiocarcinoma biliary diseases background cholangiocarcinoma cca fatal cancer bile duct epithelial cell lining misdiagnosis cca biliary diseases may occur due similarity clinical manifestations blood tests resulting inappropriate delayed treatment thus accurate less invasive method differentiating cca biliary diseases inevitable methods quantified methylation opcml hoxa9 hoxd9 serum cell free dna cfdna cca patients biliary diseases using methylation sensitive high resolution melting ms hrm potency differential biomarkers cca biliary diseases also evaluated using receiver operating characteristic roc curves results significant difference methylation levels opcml hoxd9 observed serum cfdna cca compared biliary diseases assessment serum cfdna methylation opcml hoxd9 differential biomarkers cca biliary diseases showed area curve auc 0 850 0 759 0 941 opcml sensitivity specificity positive predictive value ppv negative predictive value npv accuracy 80 00 90 00 88 88 81 81 85 00 respectively auc hoxd9 0 789 0 686 0 892 sensitivity specificity ppv npv accuracy 67 50 90 00 87 09 73 46 78 75 respectively combined marker opcml hoxd9 showed sensitivity specificity ppv npv 62 50 100 100 72 72 respectively may helpful prevent misdiagnosis cca biliary diseases conclusions findings suggest application serum cfdna methylation opcml hoxd9 differential diagnosis cca biliary diseases due less invasiveness clinically practical method may benefit patients preventing misdiagnosis cca avoiding unnecessary surgical intervention stn","probabilities":0.9467213,"Title":"Serum Cell-Free Dna Methylation Of Opcml And Hoxd9 As A Biomarker That May Aid In Differential Diagnosis Between Cholangiocarcinoma And Other Biliary Diseases","Abstract":"Background: Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct epithelial cell lining. The misdiagnosis of CCA and other biliary diseases may occur due to the similarity of clinical manifestations and blood tests resulting in inappropriate or delayed treatment. Thus, an accurate and less-invasive method for differentiating CCA from other biliary diseases is inevitable. \r\n\r\n Methods: We quantified methylation of OPCML, HOXA9, and HOXD9 in serum cell-free DNA (cfDNA) of CCA patients and other biliary diseases using methylation-sensitive high-resolution melting (MS-HRM). Their potency as differential biomarkers between CCA and other biliary diseases was also evaluated by using receiver operating characteristic (ROC) curves. \r\n\r\n Results: The significant difference of methylation levels of OPCML and HOXD9 was observed in serum cfDNA of CCA compared to other biliary diseases. Assessment of serum cfDNA methylation of OPCML and HOXD9 as differential biomarkers of CCA and other biliary diseases showed the area under curve (AUC) of 0.850 (0.759-0.941) for OPCML which sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 80.00%, 90.00%, 88.88%, 81.81%, and 85.00%, respectively. The AUC of HOXD9 was 0.789 (0.686-0.892) with sensitivity, specificity, PPV, NPV, and accuracy of 67.50%, 90.00%, 87.09%, 73.46%, and 78.75%, respectively. The combined marker between OPCML and HOXD9 showed sensitivity, specificity, PPV, and NPV of 62.50%, 100%, 100%, and 72.72%, respectively, which may be helpful to prevent a misdiagnosis between CCA and other biliary diseases. \r\n\r\n Conclusions: Our findings suggest the application of serum cfDNA methylation of OPCML and HOXD9 for differential diagnosis of CCA and other biliary diseases due to its less invasiveness and clinically practical method which may benefit the patients by preventing the misdiagnosis of CCA and avoiding unnecessary surgical intervention.","Source":"STN","category":"ANIMAL","training_data":"Serum Cell-Free Dna Methylation Of Opcml And Hoxd9 As A Biomarker That May Aid In Differential Diagnosis Between Cholangiocarcinoma And Other Biliary Diseases Background: Cholangiocarcinoma (CCA) is a fatal cancer of the bile duct epithelial cell lining. The misdiagnosis of CCA and other biliary diseases may occur due to the similarity of clinical manifestations and blood tests resulting in inappropriate or delayed treatment. Thus, an accurate and less-invasive method for differentiating CCA from other biliary diseases is inevitable. \r\n\r\n Methods: We quantified methylation of OPCML, HOXA9, and HOXD9 in serum cell-free DNA (cfDNA) of CCA patients and other biliary diseases using methylation-sensitive high-resolution melting (MS-HRM). Their potency as differential biomarkers between CCA and other biliary diseases was also evaluated by using receiver operating characteristic (ROC) curves. \r\n\r\n Results: The significant difference of methylation levels of OPCML and HOXD9 was observed in serum cfDNA of CCA compared to other biliary diseases. Assessment of serum cfDNA methylation of OPCML and HOXD9 as differential biomarkers of CCA and other biliary diseases showed the area under curve (AUC) of 0.850 (0.759-0.941) for OPCML which sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 80.00%, 90.00%, 88.88%, 81.81%, and 85.00%, respectively. The AUC of HOXD9 was 0.789 (0.686-0.892) with sensitivity, specificity, PPV, NPV, and accuracy of 67.50%, 90.00%, 87.09%, 73.46%, and 78.75%, respectively. The combined marker between OPCML and HOXD9 showed sensitivity, specificity, PPV, and NPV of 62.50%, 100%, 100%, and 72.72%, respectively, which may be helpful to prevent a misdiagnosis between CCA and other biliary diseases. \r\n\r\n Conclusions: Our findings suggest the application of serum cfDNA methylation of OPCML and HOXD9 for differential diagnosis of CCA and other biliary diseases due to its less invasiveness and clinically practical method which may benefit the patients by preventing the misdiagnosis of CCA and avoiding unnecessary surgical intervention. STN","prediction_labels":"ANIMAL"},{"cleaned":"liver transplantation conventional surgery advanced hepatocellular carcinoma study intended discuss roles hepatic resection hr liver transplantation lt patients advanced hepatocellular carcinoma hcc experience literature review large hcc 10 cm hr regarded treatment choice hepatic function preserved considering frequent extrahepatic recurrence acceptable outcome curative hr lt recommended multiple hccs hr attempted different preferences worldwide hr offer acceptable survival outcome patients small oligo nodular hccs well preserved liver function recurrence pattern lowers applicability salvage lt thus primary lt suggested hcc patients major portal vein tumor thrombus hr thrombus removal performed contrast lt contraindicated hcc bile duct tumor thrombus aggressive en bloc resection lead prolongation survival consensus transplantability hcc bile duct tumor thrombus complete resection may provide survival gain lt conclusion hr lt complementary roles thus associated rather opposed multi modality treatment strategy especially patients advanced hcc provides new elds investigation diverse indications hr lt google scholar","probabilities":0.9799733,"Title":"Liver Transplantation And Conventional Surgery For Advanced Hepatocellular Carcinoma","Abstract":"This study intended to discuss the roles of hepatic resection (HR) and liver transplantation (LT) in patients with advanced hepatocellular carcinoma (HCC) through our experience and literature review. For large HCC > 10 cm, HR is regarded as the treatment of choice when hepatic function is preserved. Considering frequent extrahepatic recurrence and acceptable outcome after curative HR, LT has not been recommended. For multiple HCCs, HR has been attempted in different preferences worldwide. HR can offer acceptable survival outcome for patients with small oligo-nodular HCCs and well-preserved liver function. Recurrence pattern lowers the applicability of salvage LT, thus primary LT is suggested. For HCC patients with major portal vein tumor thrombus, HR with thrombus removal can be performed, in contrast LT is contraindicated. For HCC with bile duct tumor thrombus, aggressive en bloc resection can lead to prolongation of survival. There is no consensus on transplantability of HCC with bile duct tumor thrombus, but complete resection may provide survival gain after LT. In conclusion, HR and LT have complementary roles, thus they should be associated to rather than being opposed. Multi-modality treatment strategy especially, for patients with advanced HCC, provides new fields of investigation for diverse indications of HR and LT","Source":"Google Scholar","category":"HUMAN","training_data":"Liver Transplantation And Conventional Surgery For Advanced Hepatocellular Carcinoma This study intended to discuss the roles of hepatic resection (HR) and liver transplantation (LT) in patients with advanced hepatocellular carcinoma (HCC) through our experience and literature review. For large HCC > 10 cm, HR is regarded as the treatment of choice when hepatic function is preserved. Considering frequent extrahepatic recurrence and acceptable outcome after curative HR, LT has not been recommended. For multiple HCCs, HR has been attempted in different preferences worldwide. HR can offer acceptable survival outcome for patients with small oligo-nodular HCCs and well-preserved liver function. Recurrence pattern lowers the applicability of salvage LT, thus primary LT is suggested. For HCC patients with major portal vein tumor thrombus, HR with thrombus removal can be performed, in contrast LT is contraindicated. For HCC with bile duct tumor thrombus, aggressive en bloc resection can lead to prolongation of survival. There is no consensus on transplantability of HCC with bile duct tumor thrombus, but complete resection may provide survival gain after LT. In conclusion, HR and LT have complementary roles, thus they should be associated to rather than being opposed. Multi-modality treatment strategy especially, for patients with advanced HCC, provides new fields of investigation for diverse indications of HR and LT Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"enrichment multiple immune checkpoints cholangiocarcinoma cancer stem cells abstract available google scholar","probabilities":0.9799733,"Title":"Enrichment Of Multiple Immune Checkpoints In Cholangiocarcinoma Cancer Stem Cells","Abstract":"Abstract not available","Source":"Google Scholar","category":"ANIMAL","training_data":"Enrichment Of Multiple Immune Checkpoints In Cholangiocarcinoma Cancer Stem Cells Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"distant metastasis risk stratification patients undergoing curative resection followed adjuvant chemoradiation extrahepatic bile duct cancer purpose analyze prognostic factors predicting distant metastasis patients undergoing adjuvant chemoradiation extrahepatic bile duct ehbd cancer methods materials january 1995 august 2006 166 patients ehbd cancer underwent resection curative intent followed adjuvant chemoradiation 120 males 46 females median age 61 years range 34 86 postoperative radiotherapy delivered tumor bed regional lymph nodes median dose 40 gy range 34 56 gy total 157 patients also received fluoropyrimidine chemotherapy radiosensitizer fluoropyrimidine based maintenance chemotherapy administered 127 patients median follow duration 29 months results treatment failed 97 patients major pattern failure distant metastasis 76 patients 78 4 5 year distant metastasis free survival rate 49 4 common site distant failure liver n 36 multivariate analysis hilar tumor tumor size 2 cm involved lymph node poorly differentiated tumor associated inferior distant metastasis free survival p 0 0348 0 0754 0 0009 0 0078 respectively whereas stage p 0 8081 patients divided four groups based risk factors 5 year distant metastasis free survival rates patients 0 1 2 3 risk factors 86 4 59 9 32 5 0 respectively p 0 0001 conclusion despite maintenance chemotherapy distant metastasis major pattern failure patients undergoing adjuvant chemoradiation ehbd cancer resection curative intent intensified chemotherapy warranted improve treatment outcome especially multiple risk factors pubmed","probabilities":0.9799733,"Title":"Distant metastasis risk stratification for patients undergoing curative resection followed by adjuvant chemoradiation for extrahepatic bile duct cancer","Abstract":"PURPOSE: To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. METHODS AND MATERIALS: Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34-86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34-56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up duration was 29 months. RESULTS: The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size ≥ 2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0348, 0.0754, 0.0009, and 0.0078, respectively), whereas T stage was not (p = 0.8081). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 59.9%, 32.5%, and 0%, respectively (p < 0.0001). CONCLUSION: Despite maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for EHBD cancer after resection with curative intent. Intensified chemotherapy is warranted to improve the treatment outcome, especially in those with multiple risk factors.","Source":"PubMed","category":"HUMAN","training_data":"Distant metastasis risk stratification for patients undergoing curative resection followed by adjuvant chemoradiation for extrahepatic bile duct cancer PURPOSE: To analyze the prognostic factors predicting distant metastasis in patients undergoing adjuvant chemoradiation for extrahepatic bile duct (EHBD) cancer. METHODS AND MATERIALS: Between January 1995 and August 2006, 166 patients with EHBD cancer underwent resection with curative intent, followed by adjuvant chemoradiation. There were 120 males and 46 females, and median age was 61 years (range, 34-86). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes (median dose, 40 Gy; range, 34-56 Gy). A total of 157 patients also received fluoropyrimidine chemotherapy as a radiosensitizer, and fluoropyrimidine-based maintenance chemotherapy was administered to 127 patients. Median follow-up duration was 29 months. RESULTS: The treatment failed for 97 patients, and the major pattern of failure was distant metastasis (76 patients, 78.4%). The 5-year distant metastasis-free survival rate was 49.4%. The most common site of distant failure was the liver (n = 36). On multivariate analysis, hilar tumor, tumor size ≥ 2 cm, involved lymph node, and poorly differentiated tumor were associated with inferior distant metastasis-free survival (p = 0.0348, 0.0754, 0.0009, and 0.0078, respectively), whereas T stage was not (p = 0.8081). When patients were divided into four groups based on these risk factors, the 5-year distant metastasis-free survival rates for patients with 0, 1, 2, and 3 risk factors were 86.4%, 59.9%, 32.5%, and 0%, respectively (p < 0.0001). CONCLUSION: Despite maintenance chemotherapy, distant metastasis was the major pattern of failure in patients undergoing adjuvant chemoradiation for EHBD cancer after resection with curative intent. Intensified chemotherapy is warranted to improve the treatment outcome, especially in those with multiple risk factors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"elevated bile amylase level without pancreaticobiliary maljunction risk factor gallbladder carcinoma background elevated bile amylase level patients pancreaticobiliary maljunction pbm high confluence pancreaticobiliary ducts hcpbd well known risk factor gallbladder carcinoma gbc development however effects occult pancreaticobiliary reflux opr condition characterized high bile amylase level presence anatomically normal pancreaticobiliary junction gbc development remain unclear aim study assess relationship opr gbc methods clinicopathological data 52 patients preoperatively diagnosed gallbladder gb tumor 22 malignant 30 benign retrospectively reviewed patients underwent preoperative endoscopic retrograde cholangiopancreatography evaluate pancreaticobiliary junction morphology bile amylase level relationship histological diagnosis gb lesions pancreaticobiliary junction morphology bile amylase level investigated results pancreaticobiliary maljunction hcpbd normal pancreaticobiliary junction npj identified 12 nine 31 patients respectively rates gbc patients pbm hcpbd npj 58 7 12 67 6 9 29 9 31 respectively 31 patients npj 22 opr nine gbc none patients npj normal bile amylase level gbc additionally among patients npj bile amylase level significantly higher patients gbc patients benign tumors conclusions occult pancreaticobiliary reflux like pbm hcpbd risk factor gbc development stn","probabilities":0.9799733,"Title":"Elevated Bile Amylase Level Without Pancreaticobiliary Maljunction Is A Risk Factor For Gallbladder Carcinoma","Abstract":"Background: Elevated bile amylase level in patients with pancreaticobiliary maljunction (PBM) or high confluence of pancreaticobiliary ducts (HCPBD) is well known as a risk factor for gallbladder carcinoma (GBC) development. However, the effects of occult pancreaticobiliary reflux (OPR), a condition characterized by high bile amylase level in the presence of an anatomically normal pancreaticobiliary junction, on GBC development remain unclear. The aim of this study was to assess the relationship between OPR and GBC. \r\n\r\n Methods: Clinicopathological data of 52 patients who were preoperatively diagnosed with gallbladder (GB) tumor (22 malignant, 30 benign) were retrospectively reviewed. All of the patients underwent preoperative endoscopic retrograde cholangiopancreatography to evaluate pancreaticobiliary junction morphology and bile amylase level. The relationship between the histological diagnosis of GB lesions, and pancreaticobiliary junction morphology and bile amylase level were investigated. \r\n\r\n Results: Pancreaticobiliary maljunction, HCPBD, and normal pancreaticobiliary junction (NPJ) were identified in 12, nine, and 31 patients, respectively. The rates of GBC in patients with PBM, HCPBD, and NPJ were 58% (7/12), 67% (6/9), and 29% (9/31), respectively. Of the 31 patients with NPJ, 22 had OPR and nine of these had GBC. None of the patients with NPJ and normal bile amylase level had GBC. Additionally, among patients with NPJ, bile amylase level was significantly higher in patients with GBC than in patients with benign tumors. \r\n\r\n Conclusions: Occult pancreaticobiliary reflux, like PBM and HCPBD, is a risk factor for GBC development.","Source":"STN","category":"HUMAN","training_data":"Elevated Bile Amylase Level Without Pancreaticobiliary Maljunction Is A Risk Factor For Gallbladder Carcinoma Background: Elevated bile amylase level in patients with pancreaticobiliary maljunction (PBM) or high confluence of pancreaticobiliary ducts (HCPBD) is well known as a risk factor for gallbladder carcinoma (GBC) development. However, the effects of occult pancreaticobiliary reflux (OPR), a condition characterized by high bile amylase level in the presence of an anatomically normal pancreaticobiliary junction, on GBC development remain unclear. The aim of this study was to assess the relationship between OPR and GBC. \r\n\r\n Methods: Clinicopathological data of 52 patients who were preoperatively diagnosed with gallbladder (GB) tumor (22 malignant, 30 benign) were retrospectively reviewed. All of the patients underwent preoperative endoscopic retrograde cholangiopancreatography to evaluate pancreaticobiliary junction morphology and bile amylase level. The relationship between the histological diagnosis of GB lesions, and pancreaticobiliary junction morphology and bile amylase level were investigated. \r\n\r\n Results: Pancreaticobiliary maljunction, HCPBD, and normal pancreaticobiliary junction (NPJ) were identified in 12, nine, and 31 patients, respectively. The rates of GBC in patients with PBM, HCPBD, and NPJ were 58% (7/12), 67% (6/9), and 29% (9/31), respectively. Of the 31 patients with NPJ, 22 had OPR and nine of these had GBC. None of the patients with NPJ and normal bile amylase level had GBC. Additionally, among patients with NPJ, bile amylase level was significantly higher in patients with GBC than in patients with benign tumors. \r\n\r\n Conclusions: Occult pancreaticobiliary reflux, like PBM and HCPBD, is a risk factor for GBC development. STN","prediction_labels":"HUMAN"},{"cleaned":"circular rnas gastrointestinal cancers epigenetic regulators prognostic therapeutic role environmental genetic factors involved initiation development gastrointestinal cancer covalent closed circular rnas circrnas produced mechanism called back splicing mrnas highly stable show cell tissue specific expression patterns although functions microrna sponge rna binding protein sponge reported small number circrnas function thousands circrnas still unknown dysregulation circrnas reported many gi cancers involved metastasis invasion circrnas reported useful prognostic markers targets developing new treatments first describe properties biogenesis circrnas summarize recent reports circrna functions expression status potential used biomarkers gi cancers including gastric cancer colorectal cancer esophageal cancer hepatocellular carcinoma gallbladder cancer pancreatic cancer pubmed","probabilities":0.962963,"Title":"Circular RNAs and gastrointestinal cancers: Epigenetic regulators with a prognostic and therapeutic role","Abstract":"Both environmental and genetic factors are involved in the initiation and development of gastrointestinal cancer. Covalent closed circular RNAs (circRNAs) are produced by a mechanism called \"back-splicing\" from mRNAs. They are highly stable and show cell and tissue specific expression patterns. Although some functions such as \"microRNA sponge\" and \"RNA binding protein sponge\" have been reported for a small number of circRNAs, the function of thousands of other circRNAs is still unknown. Dysregulation of circRNAs has been reported in many GI cancers and are involved in metastasis and invasion. CircRNAs have been reported to be useful as prognostic markers and targets for developing new treatments. We first describe the properties and biogenesis of circRNAs. We then summarize recent reports about circRNA functions, expression status, and their potential to be used as biomarkers in GI cancers including, gastric cancer, colorectal cancer, esophageal cancer, hepatocellular carcinoma, gallbladder cancer and pancreatic cancer.","Source":"PubMed","category":"HUMAN","training_data":"Circular RNAs and gastrointestinal cancers: Epigenetic regulators with a prognostic and therapeutic role Both environmental and genetic factors are involved in the initiation and development of gastrointestinal cancer. Covalent closed circular RNAs (circRNAs) are produced by a mechanism called \"back-splicing\" from mRNAs. They are highly stable and show cell and tissue specific expression patterns. Although some functions such as \"microRNA sponge\" and \"RNA binding protein sponge\" have been reported for a small number of circRNAs, the function of thousands of other circRNAs is still unknown. Dysregulation of circRNAs has been reported in many GI cancers and are involved in metastasis and invasion. CircRNAs have been reported to be useful as prognostic markers and targets for developing new treatments. We first describe the properties and biogenesis of circRNAs. We then summarize recent reports about circRNA functions, expression status, and their potential to be used as biomarkers in GI cancers including, gastric cancer, colorectal cancer, esophageal cancer, hepatocellular carcinoma, gallbladder cancer and pancreatic cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"reasonable cholecystectomy gallbladder polyp 10 years experience background objective although incidence carcinoma high gallbladder polyps essential diagnose gallbladder cancer early stage achieve good therapeutic outcome therefore aim study define characteristics gallbladder polyps establish sound criteria surgical indications methods current study data 516 patients gallbladder polyps underwent cholecystectomy reviewed correlate clinical features histopathologic findings identify risk factors receiver operating characteristic curves rocs results among 516 patients underwent cholecystectomy 24 patients 4 6 cancerous change cancer group significantly older 65 5 years median range 35 85 non cancer group 42 years median range 23 82 p 0 001 among cancer group preoperative polyp size ultrasonography significantly larger 14 mm median range 9 30 polyps non cancer group 10 4 mm median range 1 9 45 p 0 001 using roc curve considering sensitivity specificity predicting malignant polyps 12 mm may reasonable cutoff considering malignant polyp conclusions gallbladder polyps 10 11 mm asymptomatic young patients less 50 years old low risk malignancy therefore careful wait see follow using ultrasonography strategy might appropriate immediate cholecystectomy google scholar","probabilities":0.9799733,"Title":"Reasonable Cholecystectomy Of Gallbladder Polyp - 10 Years Of Experience","Abstract":"Background and objective\nAlthough the incidence of carcinoma is not high in gallbladder polyps, it is essential to diagnose gallbladder cancer at an early stage to achieve a good therapeutic outcome. Therefore, the aim of this study was to define the characteristics of gallbladder polyps to establish sound criteria for surgical indications.\nMethods\nIn the current study, data from 516 patients with gallbladder polyps who underwent cholecystectomy were reviewed to correlate clinical features with histopathologic findings and identify risk factors with receiver-operating characteristic curves (ROCs).\nResults\nAmong the 516 patients who underwent cholecystectomy, 24 patients (4.6%) had cancerous change. The cancer group was significantly older (65.5 years (median, range 35–85)) than the non-cancer group (42 years (median, range 23–82)) (p < 0.001). Among the cancer group, the preoperative polyp size on ultrasonography was significantly larger (14 mm (median, range 9–30)) than the polyps in the non-cancer group (10.4 mm (median, range 1.9–45)) (p < 0.001). Using the ROC curve and considering the sensitivity and specificity for predicting malignant polyps, 12 mm may be a reasonable cutoff for considering a malignant polyp.\nConclusions\nGallbladder polyps with 10–11 mm in asymptomatic young patients (less than 50 years old) have low risk of malignancy, and therefore, a careful “wait and see with follow up by using ultrasonography strategy” might be more appropriate than immediate cholecystectomy.","Source":"Google Scholar","category":"HUMAN","training_data":"Reasonable Cholecystectomy Of Gallbladder Polyp - 10 Years Of Experience Background and objective\nAlthough the incidence of carcinoma is not high in gallbladder polyps, it is essential to diagnose gallbladder cancer at an early stage to achieve a good therapeutic outcome. Therefore, the aim of this study was to define the characteristics of gallbladder polyps to establish sound criteria for surgical indications.\nMethods\nIn the current study, data from 516 patients with gallbladder polyps who underwent cholecystectomy were reviewed to correlate clinical features with histopathologic findings and identify risk factors with receiver-operating characteristic curves (ROCs).\nResults\nAmong the 516 patients who underwent cholecystectomy, 24 patients (4.6%) had cancerous change. The cancer group was significantly older (65.5 years (median, range 35–85)) than the non-cancer group (42 years (median, range 23–82)) (p < 0.001). Among the cancer group, the preoperative polyp size on ultrasonography was significantly larger (14 mm (median, range 9–30)) than the polyps in the non-cancer group (10.4 mm (median, range 1.9–45)) (p < 0.001). Using the ROC curve and considering the sensitivity and specificity for predicting malignant polyps, 12 mm may be a reasonable cutoff for considering a malignant polyp.\nConclusions\nGallbladder polyps with 10–11 mm in asymptomatic young patients (less than 50 years old) have low risk of malignancy, and therefore, a careful “wait and see with follow up by using ultrasonography strategy” might be more appropriate than immediate cholecystectomy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"efficacy fluoropyrimidine based chemotherapy patients advanced biliary tract cancer failure gemcitabine plus cisplatin retrospective analysis 321 patients background aimed assess efficacy second line fluoropyrimidine based chemotherapy patients advanced biliary tract cancer btc failure gemcitabine plus cisplatin gemcis methods retrospectively examined patients histologically documented advanced btc received first line gemcis december 2010 june 2015 among 748 patients treated first line gemcis 321 43 subsequently received fluoropyrimidine based second line systemic chemotherapy results fluoropyrimidine monotherapy fluoropyrimidine platinum combination used 255 66 patients respectively patients measurable disease overall response rate orr 3 disease control rate 47 median follow 27 6 months range 0 9 70 4 months median progression free survival pfs overall survival os 1 9 months 95 confidence interval ci 1 6 2 2 6 5 months 95 ci 5 9 7 0 respectively orr significantly higher patients received fluoropyrimidine platinum combination compared received fluoropyrimidine alone 8 vs 1 p 0 009 although pfs p 0 43 os p 0 88 significantly differ groups conclusions fluoropyrimidine based chemotherapy modestly effective second line chemotherapy advanced btc patients failure gemcis fluoropyrimidine platinum combination therapy associated improved survival outcomes compared fluoropyrimidine monotherapy pubmed","probabilities":0.9799733,"Title":"Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer after failure of gemcitabine plus cisplatin: retrospective analysis of 321 patients","Abstract":"BACKGROUND: We aimed to assess the efficacy of second-line fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer (BTC) after failure of gemcitabine plus cisplatin (GEMCIS). METHODS: We retrospectively examined patients with histologically documented advanced BTC who received first-line GEMCIS between December 2010 and June 2015. Among 748 patients treated with first-line GEMCIS, 321 (43%) subsequently received fluoropyrimidine-based second-line systemic chemotherapy. RESULTS: Fluoropyrimidine monotherapy and fluoropyrimidine-platinum combination were used in 255 and 66 patients, respectively. In patients with measurable disease, the overall response rate (ORR) was 3% and disease control rate was 47%. After a median follow-up of 27.6 months (range, 0.9-70.4 months), the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval (CI), 1.6-2.2) and 6.5 months (95% CI, 5.9-7.0), respectively. The ORR was significantly higher in patients who received fluoropyrimidine-platinum combination compared with those who received fluoropyrimidine alone (8 vs 1%, P=0.009), although the PFS (P=0.43) and OS (P=0.88) did not significantly differ between these groups. CONCLUSIONS: Fluoropyrimidine-based chemotherapy was modestly effective as a second-line chemotherapy for advanced BTC patients after failure of GEMCIS. Fluoropyrimidine-platinum combination therapy was not associated with improved survival outcomes, as compared with fluoropyrimidine monotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Efficacy of fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer after failure of gemcitabine plus cisplatin: retrospective analysis of 321 patients BACKGROUND: We aimed to assess the efficacy of second-line fluoropyrimidine-based chemotherapy in patients with advanced biliary tract cancer (BTC) after failure of gemcitabine plus cisplatin (GEMCIS). METHODS: We retrospectively examined patients with histologically documented advanced BTC who received first-line GEMCIS between December 2010 and June 2015. Among 748 patients treated with first-line GEMCIS, 321 (43%) subsequently received fluoropyrimidine-based second-line systemic chemotherapy. RESULTS: Fluoropyrimidine monotherapy and fluoropyrimidine-platinum combination were used in 255 and 66 patients, respectively. In patients with measurable disease, the overall response rate (ORR) was 3% and disease control rate was 47%. After a median follow-up of 27.6 months (range, 0.9-70.4 months), the median progression-free survival (PFS) and overall survival (OS) were 1.9 months (95% confidence interval (CI), 1.6-2.2) and 6.5 months (95% CI, 5.9-7.0), respectively. The ORR was significantly higher in patients who received fluoropyrimidine-platinum combination compared with those who received fluoropyrimidine alone (8 vs 1%, P=0.009), although the PFS (P=0.43) and OS (P=0.88) did not significantly differ between these groups. CONCLUSIONS: Fluoropyrimidine-based chemotherapy was modestly effective as a second-line chemotherapy for advanced BTC patients after failure of GEMCIS. Fluoropyrimidine-platinum combination therapy was not associated with improved survival outcomes, as compared with fluoropyrimidine monotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"folfiri patients locally advanced metastatic pancreatic biliary tract carcinoma monoinstitutional experience pancreatic biliary tract carcinomas chemoresistant first line treatment gemcitabine based regimen second line scheme consolidated clinical practice aim study evaluate toxicity activity folfiri regimen first line second line chemotherapy patients pancreatic biliary tract tumors fifty four patients 30 pancreatic tumor nine gallbladder tumor 15 biliary tract tumor treated folfiri irinotecan 180 mg m day 1 leucovorin 100 mg m intravenously days 1 2 5 fluorouracil 400 mg m intravenous bolus days 1 2 600 mg m 22 h intravenously continuous infusion days 1 2 every 14 days toxicity recorded cycle according nci ctc v3 0 criteria response rate verified four cycles according recist criteria progression free survival rates well overall survival rates calculated according kaplan meier method overall toxicity mild grade 3 4 neutropenia occurred 42 6 patients grade 3 4 gastrointestinal toxicity rare folfiri first line treatment produced response rate 25 second line group 9 21 patients 42 9 obtained stable disease best response entire population median progression free survival rates 3 1 months 95 confidence interval ci 1 9 4 4 3 5 months 95 ci 2 6 4 4 respectively first line second line cohort patients median overall survival rates 14 5 months 95 ci 7 0 22 1 6 2 months 95 ci 5 4 7 0 respectively first line second line cohort patients folfiri feasible well tolerated patients pancreatic biliary tract tumors good activity first line mostly patients pancreatic cancer pubmed","probabilities":0.9799733,"Title":"FOLFIRI in patients with locally advanced or metastatic pancreatic or biliary tract carcinoma: a monoinstitutional experience","Abstract":"Pancreatic and biliary tract carcinomas are very chemoresistant. After a first-line treatment with a gemcitabine-based regimen, no second-line scheme is consolidated in clinical practice. The aim of this study was to evaluate the toxicity and the activity of the FOLFIRI regimen as first-line or second-line chemotherapy in patients with pancreatic or biliary tract tumors. Fifty-four patients (30 with pancreatic tumor, nine with gallbladder tumor, and 15 with biliary tract tumor) were treated with FOLFIRI (irinotecan 180 mg/m², day 1; leucovorin 100 mg/m² intravenously, days 1 and 2; 5-fluorouracil 400 mg/m² intravenous bolus, days 1 and 2; and 600 mg/m² in 22 h intravenously, continuous infusion days 1 and 2; every 14 days). Toxicity was recorded at each cycle according to the NCI-CTC V3.0 criteria, the response rate was verified each four cycles according to the RECIST criteria, and the progression-free survival rates as well as the overall survival rates were calculated according to the Kaplan-Meier method. Overall, the toxicity was mild. Grade 3-4 neutropenia occurred in 42.6% of patients. Grade 3-4 gastrointestinal toxicity was rare. FOLFIRI as a first-line treatment produced a response rate of 25%. In the second-line group, 9/21 patients (42.9%) obtained a stable disease as best response. In the entire population, the median progression-free survival rates were 3.1 months [95% confidence interval (CI), 1.9-4.4] and 3.5 months (95% CI, 2.6-4.4), respectively, in the first-line and the second-line cohort of patients. The median overall survival rates were 14.5 months (95% CI, 7.0-22.1) and 6.2 months (95% CI, 5.4-7.0), respectively, in the first-line and the second-line cohort of patients. FOLFIRI is feasible and well tolerated in patients with pancreatic or biliary tract tumors; it has a good activity in first line and mostly in patients with pancreatic cancer.","Source":"PubMed","category":"HUMAN","training_data":"FOLFIRI in patients with locally advanced or metastatic pancreatic or biliary tract carcinoma: a monoinstitutional experience Pancreatic and biliary tract carcinomas are very chemoresistant. After a first-line treatment with a gemcitabine-based regimen, no second-line scheme is consolidated in clinical practice. The aim of this study was to evaluate the toxicity and the activity of the FOLFIRI regimen as first-line or second-line chemotherapy in patients with pancreatic or biliary tract tumors. Fifty-four patients (30 with pancreatic tumor, nine with gallbladder tumor, and 15 with biliary tract tumor) were treated with FOLFIRI (irinotecan 180 mg/m², day 1; leucovorin 100 mg/m² intravenously, days 1 and 2; 5-fluorouracil 400 mg/m² intravenous bolus, days 1 and 2; and 600 mg/m² in 22 h intravenously, continuous infusion days 1 and 2; every 14 days). Toxicity was recorded at each cycle according to the NCI-CTC V3.0 criteria, the response rate was verified each four cycles according to the RECIST criteria, and the progression-free survival rates as well as the overall survival rates were calculated according to the Kaplan-Meier method. Overall, the toxicity was mild. Grade 3-4 neutropenia occurred in 42.6% of patients. Grade 3-4 gastrointestinal toxicity was rare. FOLFIRI as a first-line treatment produced a response rate of 25%. In the second-line group, 9/21 patients (42.9%) obtained a stable disease as best response. In the entire population, the median progression-free survival rates were 3.1 months [95% confidence interval (CI), 1.9-4.4] and 3.5 months (95% CI, 2.6-4.4), respectively, in the first-line and the second-line cohort of patients. The median overall survival rates were 14.5 months (95% CI, 7.0-22.1) and 6.2 months (95% CI, 5.4-7.0), respectively, in the first-line and the second-line cohort of patients. FOLFIRI is feasible and well tolerated in patients with pancreatic or biliary tract tumors; it has a good activity in first line and mostly in patients with pancreatic cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"improving patient selection selective internal radiation therapy intra hepatic cholangiocarcinoma meta regression study background aims selective internal radiation therapy sirt emerging potential therapy unresectable intra hepatic cholangiocarcinoma icca able prolong life expectancy aim study collect available literature meta analyse data results investigate sources heterogeneity meta regression approach suggesting sirt valuable option methods systematic review studies published 1 september 2016 pubmed scopus databases performed patient survival primary outcome measure meta analysis performed using random effects model meta regression applied investigate relationships existing clinical tumour features primary outcome results nine observational studies included analysis involving 224 patients 1 2 3 year pooled survival estimates 55 7 33 1 20 2 clinical tumour characteristics showed medium considerable heterogeneity 2 50 meta regression analysis showed determinants best survivals presence mass forming icca type median survival 19 9 months vs 8 1 months infiltrative type p 002 also accounted heterogeneity included studies residual 2 0 sirt first line therapy median survival 24 months vs 11 5 months non na ve patients p 048 adoption concomitant chemotherapy median survival 19 5 months vs 5 5 months patients receiving chemotherapy p 042 conclusions considerable heterogeneity studies highlighting indications sirt extremely varied ameliorate sirt results na ve patients mass forming icca selected best candidates possibility adding concomitant standard chemotherapy pubmed","probabilities":0.9799733,"Title":"Improving patient selection for selective internal radiation therapy of intra-hepatic cholangiocarcinoma: A meta-regression study","Abstract":"BACKGROUND & AIMS: Selective internal radiation therapy (SIRT) is emerging as a potential therapy for unresectable intra-hepatic cholangiocarcinoma (iCCA) able to prolong life-expectancy. Aim of this study was to collect available literature meta-analyse data and results and investigate sources of heterogeneity through a meta-regression approach before suggesting SIRT as a valuable option. METHODS: A systematic review of studies published until 1 September 2016 in PubMed and Scopus databases was performed. Patient survival was the primary outcome measure. Meta-analysis was performed using a random-effects model. Meta-regression was applied to investigate relationships existing between clinical and tumour features and the primary outcome. RESULTS: Nine observational studies were included in the analysis involving 224 patients. The 1-, 2- and 3-year pooled survival estimates were 55.7%, 33.1% and 20.2%. Clinical and tumour characteristics showed medium-to-considerable heterogeneity (I(2) >50%). Meta-regression analysis showed that determinants of best survivals were the presence of mass-forming iCCA type (median survival=19.9 months vs 8.1 months for the infiltrative type; P=.002) that also accounted for most of the heterogeneity between included studies (residual I(2) =0); SIRT as first-line therapy (median survival=24 months vs 11.5 months for non-naïve patients; P=.048) and the adoption of concomitant chemotherapy (median survival 19.5 months vs 5.5 months in patients not receiving chemotherapy; P=.042). CONCLUSIONS: There is considerable heterogeneity between studies highlighting that indications for SIRT are extremely varied. To ameliorate SIRT results naïve patients with mass-forming iCCA should be selected as the best candidates with the possibility of adding concomitant standard chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Improving patient selection for selective internal radiation therapy of intra-hepatic cholangiocarcinoma: A meta-regression study BACKGROUND & AIMS: Selective internal radiation therapy (SIRT) is emerging as a potential therapy for unresectable intra-hepatic cholangiocarcinoma (iCCA) able to prolong life-expectancy. Aim of this study was to collect available literature meta-analyse data and results and investigate sources of heterogeneity through a meta-regression approach before suggesting SIRT as a valuable option. METHODS: A systematic review of studies published until 1 September 2016 in PubMed and Scopus databases was performed. Patient survival was the primary outcome measure. Meta-analysis was performed using a random-effects model. Meta-regression was applied to investigate relationships existing between clinical and tumour features and the primary outcome. RESULTS: Nine observational studies were included in the analysis involving 224 patients. The 1-, 2- and 3-year pooled survival estimates were 55.7%, 33.1% and 20.2%. Clinical and tumour characteristics showed medium-to-considerable heterogeneity (I(2) >50%). Meta-regression analysis showed that determinants of best survivals were the presence of mass-forming iCCA type (median survival=19.9 months vs 8.1 months for the infiltrative type; P=.002) that also accounted for most of the heterogeneity between included studies (residual I(2) =0); SIRT as first-line therapy (median survival=24 months vs 11.5 months for non-naïve patients; P=.048) and the adoption of concomitant chemotherapy (median survival 19.5 months vs 5.5 months in patients not receiving chemotherapy; P=.042). CONCLUSIONS: There is considerable heterogeneity between studies highlighting that indications for SIRT are extremely varied. To ameliorate SIRT results naïve patients with mass-forming iCCA should be selected as the best candidates with the possibility of adding concomitant standard chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impacts postoperative complications patients intrahepatic cholangiocarcinoma curative operations background postoperative complication one indicator poor prognosis patients several gastroenterological cancers curative operations herein examined prognostic impacts postoperative complications patients intrahepatic cholangiocarcinoma curative operations methods retrospectively analyzed 60 patients intrahepatic cholangiocarcinoma underwent primary curative operations june 2002 february 2016 prognostic impacts postoperative complications analyzed using log rank test cox proportional hazard model results postoperative complications clavien dindo classification grade 3 occurred 13 patients 21 7 overall survival patients without postoperative complications significantly better patients postoperative complications p 0 025 postoperative complications independent prognostic factor overall survival hazard ratio 3 02 p 0 030 addition bile duct resection reconstruction odds ratio 59 1 p 0 002 hepatitis c virus antibody positive odds ratio 7 14 p 0 022 lymph node dissection odds ratio 6 28 p 0 040 independent predictors postoperative complications conclusion postoperative complications may independent predictor poorer survival patients intrahepatic cholangiocarcinoma curative operations lymph node dissection bile duct resection reconstruction risk factors postoperative complications therefore pay attentions perform lymph node dissections bile duct resection reconstruction patients intrahepatic cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations","Abstract":"BACKGROUND: The postoperative complication is one of an indicator of poor prognosis in patients with several gastroenterological cancers after curative operations. We, herein, examined prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations. METHODS: We retrospectively analyzed 60 patients with intrahepatic cholangiocarcinoma who underwent primary curative operations from June 2002 to February 2016. Prognostic impacts of postoperative complications were analyzed using log-rank test and Cox proportional hazard model. RESULTS: Postoperative complications (Clavien-Dindo classification grade 3 or more) occurred in 13 patients (21.7%). Overall survival of patients without postoperative complications was significantly better than that of patients with postoperative complications (p = 0.025). Postoperative complications are independent prognostic factor of overall survival (hazard ratio 3.02; p = 0.030). In addition, bile duct resection and reconstruction (Odds ratio 59.1; p = 0.002) and hepatitis C virus antibody positive (Odds ratio 7.14; p= 0.022), and lymph node dissection (Odds ratio 6.28; p = 0.040) were independent predictors of postoperative complications. CONCLUSION: Postoperative complications may be an independent predictor of poorer survival in patients with intrahepatic cholangiocarcinoma after curative operations. Lymph node dissection and bile duct resection and reconstruction were risk factors for postoperative complications, therefore we should pay attentions to perform lymph node dissections, bile duct resection and reconstruction in patients with intrahepatic cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations BACKGROUND: The postoperative complication is one of an indicator of poor prognosis in patients with several gastroenterological cancers after curative operations. We, herein, examined prognostic impacts of postoperative complications in patients with intrahepatic cholangiocarcinoma after curative operations. METHODS: We retrospectively analyzed 60 patients with intrahepatic cholangiocarcinoma who underwent primary curative operations from June 2002 to February 2016. Prognostic impacts of postoperative complications were analyzed using log-rank test and Cox proportional hazard model. RESULTS: Postoperative complications (Clavien-Dindo classification grade 3 or more) occurred in 13 patients (21.7%). Overall survival of patients without postoperative complications was significantly better than that of patients with postoperative complications (p = 0.025). Postoperative complications are independent prognostic factor of overall survival (hazard ratio 3.02; p = 0.030). In addition, bile duct resection and reconstruction (Odds ratio 59.1; p = 0.002) and hepatitis C virus antibody positive (Odds ratio 7.14; p= 0.022), and lymph node dissection (Odds ratio 6.28; p = 0.040) were independent predictors of postoperative complications. CONCLUSION: Postoperative complications may be an independent predictor of poorer survival in patients with intrahepatic cholangiocarcinoma after curative operations. Lymph node dissection and bile duct resection and reconstruction were risk factors for postoperative complications, therefore we should pay attentions to perform lymph node dissections, bile duct resection and reconstruction in patients with intrahepatic cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"assessment liver function evaluation long term outcomes intrahepatic cholangiocarcinoma multi institutional analysis 620 patients background liver function routine laboratory test prior curative liver resection remains unclear whether albumin bilirubin albi grade albumin alkaline phosphatase ratio aapr predict long term outcomes surgically treated patients intrahepatic cholangiocarcinoma icc methods study investigated correlation albi grade aapr overall survival os liver resection compared accuracy child pugh score harrell concordance index c index akaike information criterion aic used compare accuracy models results total 620 icc patients included 477 derivation cohort 143 validation 0 348 identified cutoff value aapr calculating youden index derivation cohort elevated albi grade associated worse prognosis hazard ratio hr 1 751 95 confidence interval ci 1 329 2 306 decreased aapr value correlated shorter os hr 1 969 95 ci 1 552 2 497 multivariate analysis suggested albi grade aapr ca19 9 tumor number microvascular invasion independent prognostic predictors os albi grade aapr showed accuracy evaluating os surgically treated icc patients child pugh score c index 0 559 0 600 vs 0 528 aic 3023 84 3007 73 vs 3034 66 findings validated independent cohort another clinical center conclusions importantly albi grade aapr showed greater discriminatory power child pugh score assessing long term outcomes following hepatectomy icc aapr accurate albi grade beneficial consider albi grade aapr useful surrogate markers identify patients risk poor postoperative outcomes stn","probabilities":0.9799733,"Title":"Assessment Of Liver Function For Evaluation Of Long-Term Outcomes Of Intrahepatic Cholangiocarcinoma: A Multi-Institutional Analysis Of 620 Patients","Abstract":"Background: Liver function is a routine laboratory test prior to curative liver resection. It remains unclear whether the albumin-bilirubin (ALBI) grade and albumin-to-alkaline phosphatase ratio (AAPR) can predict long-term outcomes of surgically treated patients with intrahepatic cholangiocarcinoma (ICC). Methods: This study investigated the correlation between ALBI grade and AAPR with overall survival (OS) after liver resection and then compared their accuracy to the Child-Pugh score. Harrell's concordance index (C-index) and Akaike information criterion (AIC) were used to compare accuracy of models. Results: A total of 620 ICC patients were included, 477 in derivation cohort and 143 for validation. 0.348 was identified as the cutoff value for AAPR after calculating the Youden index. In the derivation cohort, elevated ALBI grade was associated with worse prognosis [hazard ratio (HR): 1.751, 95% confidence interval (CI): 1.329 to 2.306], and a decreased AAPR value was correlated with shorter OS (HR: 1.969, 95% CI: 1.552 to 2.497). Multivariate analysis suggested that the ALBI grade, AAPR, CA19-9, tumor number, and microvascular invasion were independent prognostic predictors for OS. ALBI grade and AAPR showed more accuracy in evaluating OS for surgically treated ICC patients than the Child-Pugh score (C-index: 0.559, 0.600 vs. 0.528; AIC: 3023.84, 3007.73 vs. 3034.66). Our findings were validated in an independent cohort from another clinical center. Conclusions: Importantly, the ALBI grade and AAPR showed greater discriminatory power than the Child-Pugh score in assessing long-term outcomes following hepatectomy for ICC. The AAPR was more accurate than the ALBI grade. It was beneficial to consider the ALBI grade and AAPR as useful surrogate markers to identify patients at risk of poor postoperative outcomes.","Source":"STN","category":"HUMAN","training_data":"Assessment Of Liver Function For Evaluation Of Long-Term Outcomes Of Intrahepatic Cholangiocarcinoma: A Multi-Institutional Analysis Of 620 Patients Background: Liver function is a routine laboratory test prior to curative liver resection. It remains unclear whether the albumin-bilirubin (ALBI) grade and albumin-to-alkaline phosphatase ratio (AAPR) can predict long-term outcomes of surgically treated patients with intrahepatic cholangiocarcinoma (ICC). Methods: This study investigated the correlation between ALBI grade and AAPR with overall survival (OS) after liver resection and then compared their accuracy to the Child-Pugh score. Harrell's concordance index (C-index) and Akaike information criterion (AIC) were used to compare accuracy of models. Results: A total of 620 ICC patients were included, 477 in derivation cohort and 143 for validation. 0.348 was identified as the cutoff value for AAPR after calculating the Youden index. In the derivation cohort, elevated ALBI grade was associated with worse prognosis [hazard ratio (HR): 1.751, 95% confidence interval (CI): 1.329 to 2.306], and a decreased AAPR value was correlated with shorter OS (HR: 1.969, 95% CI: 1.552 to 2.497). Multivariate analysis suggested that the ALBI grade, AAPR, CA19-9, tumor number, and microvascular invasion were independent prognostic predictors for OS. ALBI grade and AAPR showed more accuracy in evaluating OS for surgically treated ICC patients than the Child-Pugh score (C-index: 0.559, 0.600 vs. 0.528; AIC: 3023.84, 3007.73 vs. 3034.66). Our findings were validated in an independent cohort from another clinical center. Conclusions: Importantly, the ALBI grade and AAPR showed greater discriminatory power than the Child-Pugh score in assessing long-term outcomes following hepatectomy for ICC. The AAPR was more accurate than the ALBI grade. It was beneficial to consider the ALBI grade and AAPR as useful surrogate markers to identify patients at risk of poor postoperative outcomes. STN","prediction_labels":"HUMAN"},{"cleaned":"predictive factors survival cholangiocarcinoma 5 years experience introduction patients cholagiocarcinoma present unresectable disease diagnosis extremely poor prognosis average five year survival rate 5 10 percent undergo potentially curative resection tumor free margins obtained less half patients 12 aims methods analyze survival patients cholangicarcinoma according clinical therapeutic options retrospective study patients diagnosis cholangiocarcinoma 2008 2013 tertiary referral center kaplan meier survival curves used alpha 0 05 results included 71 patients 39 male median age 71 years diagnosis mortality rate follow period 79 37 3 months 42 6 months 51 12 months median survival 44 weeks p25 75 8 90 higher level survival 3 6 12 months associated chemotherapy treatment p 0 002 p 0 001 p 0 003 respectively lower levels ca 19 9 p 0 001 p 0 009 p 0 013 surgical treatment p50 001 tnm r0 p 0 006 p 0 031 p 0 039 metastization diagnosis p50 001 p 0 006 p 0 002 survival first trimester associated tnm n0 p 0 022 survival first year associated higher levels albumin p 0 032 lower levels alkaline phosphatase p 0 020 younger age p 0 038 fewer days beginning symptoms diagnosis date p 0 029 analysis kaplan meier curves showed association survival absence metastization diagnosis p50 001 surgical treatment p50 001 chemotherapy treatment p 0 009 terms survival 3 6 12 months therapeutic surgery mestastization associated independently logistic regression conclusion factors determine greater survival surgical treatment chemotherapy absence metastization diagnosis seems related medium term survival google scholar","probabilities":0.9799733,"Title":"Predictive Factors Of Survival In Cholangiocarcinoma: A 5-Years Experience","Abstract":"INTRODUCTION: Most patients with cholagiocarcinoma present an unresectable disease at diagnosis with an extremely poor prognosis, an average five-year survival rate of 5 to 10 percent. Those, who undergo potentially curative resection, tumor-free margins can be obtained in only less than half of the patients [12]. AIMS & METHODS: To analyze the survival of patients with cholangicarcinoma according to clinical and therapeutic options. Retrospective study of patients with diagnosis of cholangiocarcinoma between 2008 and 2013 in a tertiary referral center. The Kaplan-Meier survival curves were used, alpha¼0.05. RESULTS: We included 71 patients (39 male) with a median age of 71 years at diagnosis. The mortality rate during the follow-up period was 79% (37% at 3 months, 42% at 6 months and 51% at 12 months). The median survival was 44 weeks (P25-75: 8-90). A higher level of survival at 3, 6 and 12 months was associated with chemotherapy treatment (p¼0.002, p¼0.001, p¼0.003, respectively), lower levels of CA-19.9 (p¼0.001, p¼0.009, p¼0.013), surgical treatment (p50.001), TNM-R0 (p¼0.006, p¼0.031, p¼0.039) and no metastization at diagnosis (p50.001, p¼0.006, p¼0.002). Survival in the first trimester was associated with TNM-N0 (p¼0.022). Survival in the first year was associated with higher levels of albumin (p¼0.032), lower levels of alkaline phosphatase (p¼0.020), younger age (p¼0.038) and fewer days between the beginning of the symptoms until the diagnosis date (p¼0.029). The analysis of the Kaplan-Meier curves showed an association between survival, absence of metastization at diagnosis (p50.001), surgical treatment (p50.001) and chemotherapy treatment (p¼0.009). In terms of survival at 3, 6 and 12 months, the therapeutic surgery and the mestastization were associated independently in the logistic regression. CONCLUSION: The factors that determine a greater survival are surgical treatment and chemotherapy. Absence of metastization at diagnosis seems to be related to a medium-term survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Predictive Factors Of Survival In Cholangiocarcinoma: A 5-Years Experience INTRODUCTION: Most patients with cholagiocarcinoma present an unresectable disease at diagnosis with an extremely poor prognosis, an average five-year survival rate of 5 to 10 percent. Those, who undergo potentially curative resection, tumor-free margins can be obtained in only less than half of the patients [12]. AIMS & METHODS: To analyze the survival of patients with cholangicarcinoma according to clinical and therapeutic options. Retrospective study of patients with diagnosis of cholangiocarcinoma between 2008 and 2013 in a tertiary referral center. The Kaplan-Meier survival curves were used, alpha¼0.05. RESULTS: We included 71 patients (39 male) with a median age of 71 years at diagnosis. The mortality rate during the follow-up period was 79% (37% at 3 months, 42% at 6 months and 51% at 12 months). The median survival was 44 weeks (P25-75: 8-90). A higher level of survival at 3, 6 and 12 months was associated with chemotherapy treatment (p¼0.002, p¼0.001, p¼0.003, respectively), lower levels of CA-19.9 (p¼0.001, p¼0.009, p¼0.013), surgical treatment (p50.001), TNM-R0 (p¼0.006, p¼0.031, p¼0.039) and no metastization at diagnosis (p50.001, p¼0.006, p¼0.002). Survival in the first trimester was associated with TNM-N0 (p¼0.022). Survival in the first year was associated with higher levels of albumin (p¼0.032), lower levels of alkaline phosphatase (p¼0.020), younger age (p¼0.038) and fewer days between the beginning of the symptoms until the diagnosis date (p¼0.029). The analysis of the Kaplan-Meier curves showed an association between survival, absence of metastization at diagnosis (p50.001), surgical treatment (p50.001) and chemotherapy treatment (p¼0.009). In terms of survival at 3, 6 and 12 months, the therapeutic surgery and the mestastization were associated independently in the logistic regression. CONCLUSION: The factors that determine a greater survival are surgical treatment and chemotherapy. Absence of metastization at diagnosis seems to be related to a medium-term survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"comparative secretome analysis cholangiocarcinoma cell line three dimensional culture cholangiocarcinoma cca lethal malignancy occurs relatively high incidence thailand cancer often difficult diagnose associated high mortality secretome containing secreted proteins cells potentially useful biomarkers cancers since three dimensional 3d cell culture may mimic growth characteristics microenvironment solid tumors vivo better monolayer culture developed culture cca natural collagen based scaffold enable analysis secretome 2de results indicated cca growth 3d environment alters cell shape significantly enhances extracellular matrix deposition interestingly secreted proteins detected 3d culture compared monolayer culture secretome analysis using 2de coupled lc ms ms demonstrated 10 secreted proteins uniquely found 3d culture moreover 25 proteins enriched 3d culture compared monolayer culture including 14 3 3 triosephosphate isomerase phosphoglycerate mutase 1 enolase l plastin immunoblotting used confirm presence l plastin conditioned media cca hepatocellular carcinoma hcc cell lines results revealed l plastin actin bundling protein uniquely expressed cca cell line promising biomarker differential diagnosis cca compared hcc stn","probabilities":0.9467213,"Title":"Comparative Secretome Analysis Of Cholangiocarcinoma Cell Line In Three-Dimensional Culture","Abstract":"Cholangiocarcinoma (CCA) is a lethal malignancy which occurs with relatively high incidence in Thailand. This cancer is often difficult to diagnose and associated with high mortality. The secretome, containing the secreted proteins from cells, are potentially useful as biomarkers of cancers. Since three-dimensional (3D) cell culture may mimic growth characteristics and microenvironment of solid tumors in vivo better than monolayer culture, we have developed culture of CCA in natural collagen-based scaffold, to enable analysis of the secretome by 2DE. Our results indicated that CCA growth in 3D environment alters cell shape significantly and enhances extracellular matrix deposition. Interestingly, more secreted proteins were detected from 3D culture compared to monolayer culture. Secretome analysis using 2DE coupled with LC-MS/MS demonstrated 10 secreted proteins uniquely found in 3D culture. Moreover, 25 proteins were enriched in 3D culture compared to monolayer culture, including 14-3-3 σ, triosephosphate isomerase, phosphoglycerate mutase 1, α-enolase, and L-plastin. Immunoblotting was used to confirm the presence of L-plastin in conditioned media of CCA and of hepatocellular carcinoma (HCC) cell lines. The results revealed that L-plastin, an actin bundling protein, was uniquely expressed only in the CCA cell line and could be a promising biomarker for differential diagnosis of CCA compared to HCC.","Source":"STN","category":"ANIMAL","training_data":"Comparative Secretome Analysis Of Cholangiocarcinoma Cell Line In Three-Dimensional Culture Cholangiocarcinoma (CCA) is a lethal malignancy which occurs with relatively high incidence in Thailand. This cancer is often difficult to diagnose and associated with high mortality. The secretome, containing the secreted proteins from cells, are potentially useful as biomarkers of cancers. Since three-dimensional (3D) cell culture may mimic growth characteristics and microenvironment of solid tumors in vivo better than monolayer culture, we have developed culture of CCA in natural collagen-based scaffold, to enable analysis of the secretome by 2DE. Our results indicated that CCA growth in 3D environment alters cell shape significantly and enhances extracellular matrix deposition. Interestingly, more secreted proteins were detected from 3D culture compared to monolayer culture. Secretome analysis using 2DE coupled with LC-MS/MS demonstrated 10 secreted proteins uniquely found in 3D culture. Moreover, 25 proteins were enriched in 3D culture compared to monolayer culture, including 14-3-3 σ, triosephosphate isomerase, phosphoglycerate mutase 1, α-enolase, and L-plastin. Immunoblotting was used to confirm the presence of L-plastin in conditioned media of CCA and of hepatocellular carcinoma (HCC) cell lines. The results revealed that L-plastin, an actin bundling protein, was uniquely expressed only in the CCA cell line and could be a promising biomarker for differential diagnosis of CCA compared to HCC. STN","prediction_labels":"ANIMAL"},{"cleaned":"association seropositivity helicobacter species biliary tract cancer atbc study helicobacter detected human bile hepatobiliary tissue despite evidence helicobacter species promote gallstone formation hepatobiliary tumors laboratory studies remains unclear whether helicobacter species contribute cancers humans used multiplex panel assess whether seropositivity 15 helicobacter pylori proteins associated subsequent incidence hepatobiliary cancers finnish alpha tocopherol beta carotene cancer prevention atbc study included 64 biliary cancers 122 liver cancers 224 age matched controls occurred course 22 years helicobacter pylori seropositivity defined positive 4 antigens odds ratios 95 confidence intervals adjusted major hepatobiliary cancer risk factors among controls 88 seropositive h pylori baseline among subsequently developed hepatobiliary cancer prevalence seropositivity higher 100 gallbladder cancer 97 extrahepatic bile duct cancer 91 ampula vater cancer 96 intrahepatic bile duct cancer 94 hepatocellular carcinoma although gallbladder cancer calculated sites 7 01 95 confidence interval ci 0 79 62 33 2 21 0 19 25 52 10 67 0 76 150 08 1 20 0 42 3 45 respectively 5 47 95 ci 1 17 25 65 observed biliary tract cancers combined ors 1 observed many investigated antigens although associations statistically significant conclusion seropositivity h pylori proteins associated increased risk biliary tract cancers atbc studies needed confirm findings determine h pylori might influence risk biliary tract cancer pubmed","probabilities":0.8684211,"Title":"Association of seropositivity to Helicobacter species and biliary tract cancer in the ATBC study","Abstract":"Helicobacter have been detected in human bile and hepatobiliary tissue. Despite evidence that Helicobacter species promote gallstone formation and hepatobiliary tumors in laboratory studies, it remains unclear whether Helicobacter species contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to 15 Helicobacter pylori proteins was associated with subsequent incidence of hepatobiliary cancers in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We included 64 biliary cancers, 122 liver cancers, and 224 age-matched controls which occurred over the course of 22 years. Helicobacter pylori seropositivity was defined as those positive to ≥ 4 antigens. Odds ratios (OR) and 95% confidence intervals were adjusted for major hepatobiliary cancer risk factors. Among the controls, 88% were seropositive to H. pylori at baseline. Among those who subsequently developed hepatobiliary cancer, the prevalence of seropositivity was higher: 100% for gallbladder cancer, 97% of extrahepatic bile duct cancer, 91% of ampula of Vater cancer, 96% of intrahepatic bile duct cancer, and 94% of hepatocellular carcinoma. Although the OR for gallbladder cancer could not be calculated, the OR for the other sites were 7.01 (95% confidence interval [CI]: 0.79-62.33), 2.21 (0.19-25.52), 10.67 (0.76-150.08), and 1.20 (0.42-3.45), respectively, with an OR of 5.47 (95% CI: 1.17-25.65) observed for the biliary tract cancers combined. ORs above 1 were observed for many of the investigated antigens, although most of these associations were not statistically significant. CONCLUSION: Seropositivity to H. pylori proteins was associated with an increased risk of biliary tract cancers in ATBC. Further studies are needed to confirm our findings and to determine how H. pylori might influence the risk of biliary tract cancer.","Source":"PubMed","category":"HUMAN","training_data":"Association of seropositivity to Helicobacter species and biliary tract cancer in the ATBC study Helicobacter have been detected in human bile and hepatobiliary tissue. Despite evidence that Helicobacter species promote gallstone formation and hepatobiliary tumors in laboratory studies, it remains unclear whether Helicobacter species contribute to these cancers in humans. We used a multiplex panel to assess whether seropositivity to 15 Helicobacter pylori proteins was associated with subsequent incidence of hepatobiliary cancers in the Finnish Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. We included 64 biliary cancers, 122 liver cancers, and 224 age-matched controls which occurred over the course of 22 years. Helicobacter pylori seropositivity was defined as those positive to ≥ 4 antigens. Odds ratios (OR) and 95% confidence intervals were adjusted for major hepatobiliary cancer risk factors. Among the controls, 88% were seropositive to H. pylori at baseline. Among those who subsequently developed hepatobiliary cancer, the prevalence of seropositivity was higher: 100% for gallbladder cancer, 97% of extrahepatic bile duct cancer, 91% of ampula of Vater cancer, 96% of intrahepatic bile duct cancer, and 94% of hepatocellular carcinoma. Although the OR for gallbladder cancer could not be calculated, the OR for the other sites were 7.01 (95% confidence interval [CI]: 0.79-62.33), 2.21 (0.19-25.52), 10.67 (0.76-150.08), and 1.20 (0.42-3.45), respectively, with an OR of 5.47 (95% CI: 1.17-25.65) observed for the biliary tract cancers combined. ORs above 1 were observed for many of the investigated antigens, although most of these associations were not statistically significant. CONCLUSION: Seropositivity to H. pylori proteins was associated with an increased risk of biliary tract cancers in ATBC. Further studies are needed to confirm our findings and to determine how H. pylori might influence the risk of biliary tract cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"membrane human equilibrative nucleoside transporter 1 associated high proliferation rate worse survival resected intrahepatic cholangiocarcinoma patients receiving adjuvant treatments human equilibrative nucleoside transporter 1 hent 1 membrane nucleoside transporter mediating intracellular uptake nucleosides analogues hent 1 recently reported predictive role intrahepatic cholangiocarcinoma icc patients receiving adjuvant gemcitabine based chemotherapy biological clinical significance icc remains unsettled study investigated role hent 1 regulating tumour growth predicting survival 40 resected icc patients receiving adjuvant treatments hent 1 expression found significantly higher icc matched non tumoural liver patients harbouring hent 1 localised tumour cell membrane worse overall survival membrane hent 1 negative patients median 21 2 months vs 30 3 months p 0 031 adjusted hazard ratio 2 8 95 confidence interval 1 01 7 76 moreover membrane hent 1 positive patients higher percentage ki67 positive cells tumour tissue membrane hent 1 negative patients median 23 vs 5 p 0 0001 functional analyses icc cell lines revealed hent 1 silencing inhibited cell proliferation induced apoptosis huh 28 cells expressing hent 1 cell membrane snu 1079 cells expressing transporter cytoplasm overall findings suggest membrane hent 1 involved icc proliferation associated worse survival resected icc patients prospective studies larger cohorts required confirm results better define potential prognostic role membrane hent 1 setting patients pubmed","probabilities":1.0,"Title":"Membrane human equilibrative nucleoside transporter 1 is associated with a high proliferation rate and worse survival in resected intrahepatic cholangiocarcinoma patients not receiving adjuvant treatments","Abstract":"Human equilibrative nucleoside transporter 1 (hENT-1) is a membrane nucleoside transporter mediating the intracellular uptake of nucleosides and their analogues. hENT-1 was recently reported to have a predictive role in intrahepatic cholangiocarcinoma (iCC) patients receiving adjuvant gemcitabine-based chemotherapy, but its biological and clinical significance in iCC remains unsettled. This study investigated the role of hENT-1 in regulating tumour growth and predicting the survival of 40 resected iCC patients not receiving adjuvant treatments. hENT-1 expression was found to be significantly higher in iCC than in the matched non-tumoural liver. Patients harbouring hENT-1 localised on the tumour cell membrane had a worse overall survival than membrane hENT-1-negative patients (median 21.2 months vs 30.3 months, p = 0.031), with an adjusted hazard ratio of 2.8 (95% confidence interval 1.01-7.76). Moreover, membrane hENT-1-positive patients had a higher percentage of Ki67-positive cells in tumour tissue than membrane hENT-1-negative patients (median 23% vs 5%, p < 0.0001). Functional analyses in iCC cell lines revealed that hENT-1 silencing inhibited cell proliferation and induced apoptosis in HUH-28 cells expressing hENT-1 on the cell membrane, but not in SNU-1079 cells expressing the transporter only in the cytoplasm. Overall, these findings suggest that membrane hENT-1 is involved in iCC proliferation and associated with worse survival in resected iCC patients. Further prospective studies on larger cohorts are required to confirm these results and better define the potential prognostic role of membrane hENT-1 in this setting of patients.","Source":"PubMed","category":"HUMAN","training_data":"Membrane human equilibrative nucleoside transporter 1 is associated with a high proliferation rate and worse survival in resected intrahepatic cholangiocarcinoma patients not receiving adjuvant treatments Human equilibrative nucleoside transporter 1 (hENT-1) is a membrane nucleoside transporter mediating the intracellular uptake of nucleosides and their analogues. hENT-1 was recently reported to have a predictive role in intrahepatic cholangiocarcinoma (iCC) patients receiving adjuvant gemcitabine-based chemotherapy, but its biological and clinical significance in iCC remains unsettled. This study investigated the role of hENT-1 in regulating tumour growth and predicting the survival of 40 resected iCC patients not receiving adjuvant treatments. hENT-1 expression was found to be significantly higher in iCC than in the matched non-tumoural liver. Patients harbouring hENT-1 localised on the tumour cell membrane had a worse overall survival than membrane hENT-1-negative patients (median 21.2 months vs 30.3 months, p = 0.031), with an adjusted hazard ratio of 2.8 (95% confidence interval 1.01-7.76). Moreover, membrane hENT-1-positive patients had a higher percentage of Ki67-positive cells in tumour tissue than membrane hENT-1-negative patients (median 23% vs 5%, p < 0.0001). Functional analyses in iCC cell lines revealed that hENT-1 silencing inhibited cell proliferation and induced apoptosis in HUH-28 cells expressing hENT-1 on the cell membrane, but not in SNU-1079 cells expressing the transporter only in the cytoplasm. Overall, these findings suggest that membrane hENT-1 is involved in iCC proliferation and associated with worse survival in resected iCC patients. Further prospective studies on larger cohorts are required to confirm these results and better define the potential prognostic role of membrane hENT-1 in this setting of patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact geographical region death transplantation malignancy primary sclerosing cholangitis multicenter retrospective study international psc study group ipscsg background psc progressive cholestatic liver disease leading biliary cirrhosis high risk cholangiocarcinoma recently demonstated significant impact sex age ibd psc subytpe prognosis present sutdy analyze impact geographical region cca transplant free survival tfs method patients diagnosed psc 1980 2017 43 institutions across 22 countries 5 continents included data clinical presentation survival liver transplantation ibd phenotype heptaobiliary malignancy individual patients well centre specific strategies malignancy screening transplant allocation udca use defined time period collected adjusted cox proportional hazards models perfromed assess effect geographical region risk cca tfs result 8467 patients included 64 4 male mean age diagnosis 39years followed mean 7 3 sd 6 1 years median tfs psc diagnosis 14 years 95 ci 13 4 14 6 cca diagnosed 302 cases within first year incidence 4 02 363 patients theraafter incidence per year 0 72 heterogeneity geographical regions observed respect sex p 0 001 age p 0 001 diagnosis australia au asia south america sa southern europe se 40 patients female north america na au mean age diagnosis 40 years small duct psc frequent seand sa 11 6 11 1 regions 1 6 6 9 p 0 001 ibd assocation frequency p 0 001 northern europe ne 79 na 73 se 56 36 adjusting factors udcause cca screening significant impact geographical region cca incidence first year remained highest sa central europe ce see figure median tfs years highest se 16 1 western europe 15 7 ne 15 5 lower ce 13 9 sa 13 5 12 1 na 11 9 however adjusting mentioned factors year diagnosis transplant allocation policies years tfs highest ne reference 1 australia significantly lower ast se ce na sa see figure conclusion geographical region significantly associated different psc phenotypes independent risk factor tfs cca figure presented google scholar","probabilities":0.9799733,"Title":"Impact Of Geographical Region On Death Or Transplantation And On Malignancy In Primary Sclerosing Cholangitis-A Multicenter Retrospective Study Of The International Psc Study Group (Ipscsg)","Abstract":"Background: PSC is a progressive cholestatic liver disease leading to biliary cirrhosis and with a high risk of cholangiocarcinoma. We recently demonstated the significant impact of sex, age, IBD and PSC subytpe on prognosis. In the present sutdy, we further analyze the impact of geographical region on CCA and transplant-free survival (TFS). \nMethod(S): Patients diagnosed with PSC between 1980-2017 from 43 institutions across 22 countries and 5 continents were included. Data on clinical presentation, survival, liver transplantation, IBD-phenotype, and heptaobiliary malignancy for individual patients, as well as centre-specific strategies for malignancy screening, transplant allocation and UDCA use during defined time period was collected. Adjusted Cox proportional hazards models were perfromed to assess the effect of geographical region on risk of CCA and TFS.\nResult(s): 8467 patients were included (64.4% male, mean age at diagnosis 39years)and followed up for mean 7.3 (SD 6.1) years. Median TFS and PSC diagnosis was 14 years (95%CI 13.4-14.6). CCA was diagnosed in 302 cases within the first year (incidence 4.02%) and in 363 patients theraafter (incidence per year 0.72%). Heterogeneity between geographical regions was observed with respect to sex (p<0.001) and age (p<0.001) at diagnosis. In Australia (AU), Asia (AS), South America (SA) and Southern Europe (SE) more than 40% of patients were female and in North America (NA), AU and AS the mean age at diagnosis was >40 years. Small duct PSC was more frequent in SEand SA (11.6/11.1%) than in the other regions (1.6-6.9%, p<0.001) and an IBD assocation was more frequency (p<0.001) in Northern Europe (NE) (79%) and NA (73%) than in SE (56%) and AS (36%). After adjusting for these factors and for UDCAuse and CCA screening a significant impact of geographical region on the CCA incidence after the first year remained, and was highest in SA and Central Europe (CE)(see figure). The median TFS (Years) was highest in SE (16.1). Western Europe (WE) (15.7), NE (15.5), and lower in CE (13.9), SA (13.5), AS (12.1) and NA (11.9). However, after adjusting for the above-mentioned factors, year of diagnosis and for transplant allocation policies over the years, TFS was highest in NE (reference 1) and Australia and significantly lower in WE, AST, SE, CE, NA and SA (see figure)\nConclusion(s): The geographical region is significantly associated with different PSC phenotypes and is an independent risk factor for TFS and CCA. (Figure presented).","Source":"Google Scholar","category":"HUMAN","training_data":"Impact Of Geographical Region On Death Or Transplantation And On Malignancy In Primary Sclerosing Cholangitis-A Multicenter Retrospective Study Of The International Psc Study Group (Ipscsg) Background: PSC is a progressive cholestatic liver disease leading to biliary cirrhosis and with a high risk of cholangiocarcinoma. We recently demonstated the significant impact of sex, age, IBD and PSC subytpe on prognosis. In the present sutdy, we further analyze the impact of geographical region on CCA and transplant-free survival (TFS). \nMethod(S): Patients diagnosed with PSC between 1980-2017 from 43 institutions across 22 countries and 5 continents were included. Data on clinical presentation, survival, liver transplantation, IBD-phenotype, and heptaobiliary malignancy for individual patients, as well as centre-specific strategies for malignancy screening, transplant allocation and UDCA use during defined time period was collected. Adjusted Cox proportional hazards models were perfromed to assess the effect of geographical region on risk of CCA and TFS.\nResult(s): 8467 patients were included (64.4% male, mean age at diagnosis 39years)and followed up for mean 7.3 (SD 6.1) years. Median TFS and PSC diagnosis was 14 years (95%CI 13.4-14.6). CCA was diagnosed in 302 cases within the first year (incidence 4.02%) and in 363 patients theraafter (incidence per year 0.72%). Heterogeneity between geographical regions was observed with respect to sex (p<0.001) and age (p<0.001) at diagnosis. In Australia (AU), Asia (AS), South America (SA) and Southern Europe (SE) more than 40% of patients were female and in North America (NA), AU and AS the mean age at diagnosis was >40 years. Small duct PSC was more frequent in SEand SA (11.6/11.1%) than in the other regions (1.6-6.9%, p<0.001) and an IBD assocation was more frequency (p<0.001) in Northern Europe (NE) (79%) and NA (73%) than in SE (56%) and AS (36%). After adjusting for these factors and for UDCAuse and CCA screening a significant impact of geographical region on the CCA incidence after the first year remained, and was highest in SA and Central Europe (CE)(see figure). The median TFS (Years) was highest in SE (16.1). Western Europe (WE) (15.7), NE (15.5), and lower in CE (13.9), SA (13.5), AS (12.1) and NA (11.9). However, after adjusting for the above-mentioned factors, year of diagnosis and for transplant allocation policies over the years, TFS was highest in NE (reference 1) and Australia and significantly lower in WE, AST, SE, CE, NA and SA (see figure)\nConclusion(s): The geographical region is significantly associated with different PSC phenotypes and is an independent risk factor for TFS and CCA. (Figure presented). Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"effect external beam radiotherapy patency uncovered metallic stents patients inoperable bile duct cancer background although biliary decompression metallic stenting preferred treatment inoperable bile duct cancer bdc maintenance patency still unsatisfactory tried assess effectiveness safety external beam radiotherapy ebrt prolonging stent patency patients uncovered metallic stents method retrospectively reviewed 50 patients received endoscopic stenting 18 received ebrt rt group 32 non rt group results difference found baseline characteristics two groups although stent patency longer rt group non rt group 140 7 51 3 vs 136 4 34 9 days p 0 94 difference statistically significant lower rate stent occlusion 27 8 vs 50 0 patients p 0 12 longer overall survival 420 1 73 2 vs 269 1 41 7 days p 0 11 rt group non rt group difference statistically significant development adverse reactions differ 55 6 vs 53 1 patients p 0 91 serious adverse reaction groups p 0 99 conclusions ebrt significantly improve stent patency patients inoperable bdc uncovered metallic stents however ebrt safe future trials refined protocols better efficacy expected pubmed","probabilities":0.9799733,"Title":"Effect of external beam radiotherapy on patency of uncovered metallic stents in patients with inoperable bile duct cancer","Abstract":"BACKGROUND: Although biliary decompression with metallic stenting is the preferred treatment for inoperable bile duct cancer (BDC), maintenance of patency is still unsatisfactory. We tried to assess the effectiveness and safety of external beam radiotherapy (EBRT) for prolonging stent patency in patients having uncovered metallic stents. METHOD: We retrospectively reviewed 50 patients who received endoscopic stenting, of whom 18 received EBRT (RT group) and 32 did not (non-RT group). RESULTS: No difference was found in baseline characteristics between the two groups. Although stent patency was longer in the RT group than that in the non-RT group (140.7+/-51.3 vs 136.4+/-34.9 days, P=0.94), the difference was not statistically significant. There were a lower rate of stent occlusion (27.8% vs 50.0% of patients, P=0.12) and a longer overall survival (420.1+/-73.2 vs 269.1+/-41.7 days, P=0.11) in the RT group than in the non-RT group, and the difference again was not statistically significant. The development of adverse reactions did not differ (55.6% vs 53.1% of patients, P=0.91). There was no serious adverse reaction in both groups (P=0.99). CONCLUSIONS: EBRT did not significantly improve stent patency in patients with inoperable BDC having uncovered metallic stents. However, EBRT was safe. Future trials with refined protocols for better efficacy are expected.","Source":"PubMed","category":"HUMAN","training_data":"Effect of external beam radiotherapy on patency of uncovered metallic stents in patients with inoperable bile duct cancer BACKGROUND: Although biliary decompression with metallic stenting is the preferred treatment for inoperable bile duct cancer (BDC), maintenance of patency is still unsatisfactory. We tried to assess the effectiveness and safety of external beam radiotherapy (EBRT) for prolonging stent patency in patients having uncovered metallic stents. METHOD: We retrospectively reviewed 50 patients who received endoscopic stenting, of whom 18 received EBRT (RT group) and 32 did not (non-RT group). RESULTS: No difference was found in baseline characteristics between the two groups. Although stent patency was longer in the RT group than that in the non-RT group (140.7+/-51.3 vs 136.4+/-34.9 days, P=0.94), the difference was not statistically significant. There were a lower rate of stent occlusion (27.8% vs 50.0% of patients, P=0.12) and a longer overall survival (420.1+/-73.2 vs 269.1+/-41.7 days, P=0.11) in the RT group than in the non-RT group, and the difference again was not statistically significant. The development of adverse reactions did not differ (55.6% vs 53.1% of patients, P=0.91). There was no serious adverse reaction in both groups (P=0.99). CONCLUSIONS: EBRT did not significantly improve stent patency in patients with inoperable BDC having uncovered metallic stents. However, EBRT was safe. Future trials with refined protocols for better efficacy are expected. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact viral hepatitis b status outcomes intrahepatic cholangiocarcinoma meta analysis background aims estimate impact viral hepatitis b status outcomes intrahepatic cholangiocarcinoma methods searched pubmed embase original articles evaluated impact hepatitis b virus infection outcomes intrahepatic cholangiocarcinoma present study conducted generate odd ratios ors 95 confidence intervals cis pre identified prognostic factors overall survival recurrence results 438 studies identified eight articles compared outcomes hepatitis b virus infected patients others terms clinicopathological characteristics patients hepatitis b virus group significantly demonstrated single nodular tumor 0 7 95 ci 0 5 0 9 p 0 01 infrequent lymph node metastasis 0 5 95 ci 0 3 0 6 p 0 01 infrequent perineural infiltration 0 3 95 ci 0 2 0 8 p 0 01 significant group differences found tumor diameter vascular invasion tumor differentiation previous temporary infection seropositivity hepatitis b core antibody revealed significant impact clinicopathological characteristics survival outcomes meta analysis demonstrated hepatitis b virus group significantly better overall survival recurrence rate median survival p 0 01 conclusions results suggest hepatitis b virus infection powerful predictor favorable survival outcomes intrahepatic cholangiocarcinoma significantly affects clinicopathological characteristics viral hepatitis b status needs taken account establish therapeutic approaches pubmed","probabilities":0.9799733,"Title":"Impact of viral hepatitis B status on outcomes of intrahepatic cholangiocarcinoma: a meta-analysis","Abstract":"BACKGROUND AND AIMS: To estimate the impact of viral hepatitis B status on outcomes of intrahepatic cholangiocarcinoma. METHODS: We searched Pubmed and Embase for original articles that evaluated the impact of hepatitis B virus infection on outcomes of intrahepatic cholangiocarcinoma. The present study was conducted to generate odd ratios (ORs) with 95% confidence intervals (CIs) for pre-identified prognostic factors, overall survival, and recurrence. RESULTS: From 438 studies, we identified eight articles that compared outcomes between hepatitis B virus-infected patients and the others. In terms of clinicopathological characteristics, patients in the hepatitis B virus group significantly demonstrated single nodular tumor (OR 0.7; 95% CI 0.5-0.9; p = 0.01), infrequent lymph node metastasis (OR 0.5; 95% CI 0.3-0.6; p < 0.01), and infrequent perineural infiltration (OR 0.3; 95% CI 0.2-0.8; p < 0.01). No significant between-group differences were found in tumor diameter, vascular invasion, and tumor differentiation. Previous or temporary infection (seropositivity for hepatitis B core antibody) revealed no significant impact on clinicopathological characteristics. For survival outcomes, meta-analysis demonstrated that hepatitis B virus group had significantly better overall survival, recurrence rate, and median survival (p < 0.01). CONCLUSIONS: Our results suggest that hepatitis B virus infection is a powerful predictor of favorable survival outcomes for intrahepatic cholangiocarcinoma and significantly affects clinicopathological characteristics. Viral hepatitis B status needs to be taken into account and then establish therapeutic approaches.","Source":"PubMed","category":"HUMAN","training_data":"Impact of viral hepatitis B status on outcomes of intrahepatic cholangiocarcinoma: a meta-analysis BACKGROUND AND AIMS: To estimate the impact of viral hepatitis B status on outcomes of intrahepatic cholangiocarcinoma. METHODS: We searched Pubmed and Embase for original articles that evaluated the impact of hepatitis B virus infection on outcomes of intrahepatic cholangiocarcinoma. The present study was conducted to generate odd ratios (ORs) with 95% confidence intervals (CIs) for pre-identified prognostic factors, overall survival, and recurrence. RESULTS: From 438 studies, we identified eight articles that compared outcomes between hepatitis B virus-infected patients and the others. In terms of clinicopathological characteristics, patients in the hepatitis B virus group significantly demonstrated single nodular tumor (OR 0.7; 95% CI 0.5-0.9; p = 0.01), infrequent lymph node metastasis (OR 0.5; 95% CI 0.3-0.6; p < 0.01), and infrequent perineural infiltration (OR 0.3; 95% CI 0.2-0.8; p < 0.01). No significant between-group differences were found in tumor diameter, vascular invasion, and tumor differentiation. Previous or temporary infection (seropositivity for hepatitis B core antibody) revealed no significant impact on clinicopathological characteristics. For survival outcomes, meta-analysis demonstrated that hepatitis B virus group had significantly better overall survival, recurrence rate, and median survival (p < 0.01). CONCLUSIONS: Our results suggest that hepatitis B virus infection is a powerful predictor of favorable survival outcomes for intrahepatic cholangiocarcinoma and significantly affects clinicopathological characteristics. Viral hepatitis B status needs to be taken into account and then establish therapeutic approaches. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic molecular markers resected extrahepatic biliary tract cancers systematic review meta analysis immunohistochemically detected biomarkers better prognostic information resected extrahepatic cholangiocarcinoma guide treatment strategies potentially improve outcome study performed systematic review meta analysis identify prognostic biomarkers investigation methods relevant literature identified using medline embase web science primary end point overall survival assessed univariate analysis log hazard ratio variance calculated pooled using random effects inverse variance approach hazard ratio 95 confidence intervals calculated results thirty seven studies including 2371 patients met inclusion criteria subsequently nine biomarkers predictive os identified hr 95 ci vegf 2 32 1 57 3 44 cox 2 1 94 1 01 3 71 glut 1 2 09 1 52 2 89 cyclin d1 1 96 1 02 3 76 p16 0 68 0 47 0 98 p27 0 48 0 3 0 78 e cadherin 0 47 0 35 0 63 fascin 2 19 1 35 3 55 ki 67 1 69 1 02 2 79 conclusion meta analysis identified number prognostic biomarkers resected extrahepatic cholangiocarcinoma markers warrant investigation potential therapeutic targets validation prospective setting pubmed","probabilities":0.9799733,"Title":"Prognostic molecular markers in resected extrahepatic biliary tract cancers; a systematic review and meta-analysis of immunohistochemically detected biomarkers","Abstract":"Better prognostic information for resected extrahepatic cholangiocarcinoma could guide treatment strategies and potentially improve outcome. This study performed a systematic review and meta-analysis to identify prognostic biomarkers for further investigation. METHODS: Relevant literature was identified using Medline, EMBASE and Web of Science. Primary end point was overall survival assessed on univariate analysis. Log hazard ratio and variance were calculated and pooled using a random effects inverse variance approach. Hazard ratio and 95% confidence intervals were calculated. RESULTS: Thirty-seven studies, including 2371 patients, met the inclusion criteria. Subsequently nine biomarkers predictive of OS were identified (HR, 95% CI): VEGF (2.32, 1.57-3.44), COX-2 (1.94, 1.01-3.71), GLUT-1 (2.09, 1.52-2.89), Cyclin D1 (1.96, 1.02-3.76), p16 (0.68, 0.47-0.98), p27 (0.48, 0.3-0.78), E-Cadherin (0.47, 0.35-0.63), Fascin (2.19, 1.35-3.55), and Ki-67 (1.69, 1.02-2.79). CONCLUSION: Meta-analysis has identified a number of prognostic biomarkers for resected extrahepatic cholangiocarcinoma. These markers warrant further investigation as potential therapeutic targets and validation in a prospective setting.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic molecular markers in resected extrahepatic biliary tract cancers; a systematic review and meta-analysis of immunohistochemically detected biomarkers Better prognostic information for resected extrahepatic cholangiocarcinoma could guide treatment strategies and potentially improve outcome. This study performed a systematic review and meta-analysis to identify prognostic biomarkers for further investigation. METHODS: Relevant literature was identified using Medline, EMBASE and Web of Science. Primary end point was overall survival assessed on univariate analysis. Log hazard ratio and variance were calculated and pooled using a random effects inverse variance approach. Hazard ratio and 95% confidence intervals were calculated. RESULTS: Thirty-seven studies, including 2371 patients, met the inclusion criteria. Subsequently nine biomarkers predictive of OS were identified (HR, 95% CI): VEGF (2.32, 1.57-3.44), COX-2 (1.94, 1.01-3.71), GLUT-1 (2.09, 1.52-2.89), Cyclin D1 (1.96, 1.02-3.76), p16 (0.68, 0.47-0.98), p27 (0.48, 0.3-0.78), E-Cadherin (0.47, 0.35-0.63), Fascin (2.19, 1.35-3.55), and Ki-67 (1.69, 1.02-2.79). CONCLUSION: Meta-analysis has identified a number of prognostic biomarkers for resected extrahepatic cholangiocarcinoma. These markers warrant further investigation as potential therapeutic targets and validation in a prospective setting. PubMed","prediction_labels":"HUMAN"},{"cleaned":"circulating levels soluble urokinase plasminogen activator receptor supar predict outcome resection biliary tract cancer background aims surgical resection potentially curative therapy patients biliary tract cancer btc 5 year survival rates tumor resection remained 30 corroborating need better stratification tools identify ideal surgical candidates soluble urokinase plasminogen activator receptor supar represents mediator inflammation associated distinct types cancer study evaluated potential role supar novel biomarker patients undergoing btc resection methods tumor expression upar analyzed immunohistochemistry 108 btc samples serum levels supar analyzed elisa training validation cohort comprising total 117 patients btc 76 healthy controls results high tumoral upar expression associated adverse outcome btc resection accordingly circulating levels supar significantly elevated patients btc compared healthy controls well patients primary sclerosing cholangitis using small training set established optimal prognostic supar cut value 3 72 ng ml patients btc importantly preoperative supar serum levels cut value associated significantly impaired overall survival training validation cohort multivariate cox regression analysis including various clinicopathological parameters tumor stage markers inflammation organ dysfunction well tumor markers revealed circulating supar levels independent prognostic marker following btc resection finally high preoperative supar levels indicative acute kidney injury tumor resection conclusion circulating supar represents previously unrecognized biomarker patients resectable btc might help preoperatively identify ideal candidates liver surgery lay summary surgical resection represents curative treatment option patients biliary tract cancer patients benefit extent terms overall survival provide evidence serum levels inflammatory mediator supar indicative patient postoperative outcome might thus help identify ideal surgical candidates stn","probabilities":0.9799733,"Title":"Circulating Levels Of Soluble Urokinase Plasminogen Activator Receptor (Supar) To Predict Outcome After Resection Of Biliary Tract Cancer","Abstract":"Background & aims: Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection. \n\n Methods: Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls. \n\n Results: High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection. \n\n Conclusion: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery. \n\n Lay summary: Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates.","Source":"STN","category":"HUMAN","training_data":"Circulating Levels Of Soluble Urokinase Plasminogen Activator Receptor (Supar) To Predict Outcome After Resection Of Biliary Tract Cancer Background & aims: Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection. \n\n Methods: Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls. \n\n Results: High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection. \n\n Conclusion: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery. \n\n Lay summary: Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates. STN","prediction_labels":"HUMAN"},{"cleaned":"descriptive epidemiology cholangiocarcinoma italy background little data exist epidemiology cholangiocarcinoma italy aim focus descriptive epidemiology cholangiocarcinoma italy methods data incidence obtained italian association tumour registries mortality data obtained italian national institute statistics results progressive increase incidence age seen extra hepatic intra hepatic otherwise specified cholangiocarcinoma crude incidence rates higher extra hepatic cholangiocarcinoma intra hepatic cholangiocarcinoma men compared women increasing incidence trend observed 1988 2005 extra hepatic intra hepatic cholangiocarcinoma 3 6 yearly increase rate increase higher men women intra hepatic extra hepatic cholangiocarcinoma intra hepatic cholangiocarcinoma mortality rates progressively increased 0 15 per million 1980 5 9 per million 2003 mortality cancer surpassed extra hepatic cholangiocarcinoma mortality rates extra hepatic cholangiocarcinoma showed increasing trend 1980 1994 contrast intra hepatic cholangiocarcinoma stable slightly decreasing trend 1995 2003 observed conclusions italy cholangiocarcinoma showed progressive increase incidence mortality last two decades mainly intra hepatic cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Descriptive Epidemiology Of Cholangiocarcinoma In Italy","Abstract":"Background: Very little data exist on the epidemiology of cholangiocarcinoma in Italy. \n\n Aim: We focus on the descriptive epidemiology of cholangiocarcinoma in Italy. \n\n Methods: Data on incidence were obtained from the Italian Association of Tumour Registries while mortality data were obtained from the Italian National Institute of Statistics. \n\n Results: A progressive increase of incidence with age was seen for extra-hepatic, intra-hepatic and not otherwise specified cholangiocarcinoma. Crude incidence rates were higher for extra-hepatic cholangiocarcinoma than those for intra-hepatic cholangiocarcinoma and in men compared to women. An increasing incidence trend was observed, from 1988 to 2005, for both extra-hepatic- and intra-hepatic cholangiocarcinoma with a 3-6% yearly increase and with a rate of increase higher for men than for women and for intra-hepatic- than for extra-hepatic cholangiocarcinoma. For intra-hepatic cholangiocarcinoma, the mortality rates progressively increased from 0.15 per million in 1980 to 5.9 per million in 2003, when mortality for this cancer surpassed extra-hepatic cholangiocarcinoma. Mortality rates for extra-hepatic cholangiocarcinoma showed an increasing trend from 1980 to 1994 but, in contrast to intra-hepatic cholangiocarcinoma, a stable or slightly decreasing trend from 1995 to 2003 was observed. \n\n Conclusions: In Italy, cholangiocarcinoma showed a progressive increase in incidence and mortality in the last two decades mainly in intra-hepatic cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Descriptive Epidemiology Of Cholangiocarcinoma In Italy Background: Very little data exist on the epidemiology of cholangiocarcinoma in Italy. \n\n Aim: We focus on the descriptive epidemiology of cholangiocarcinoma in Italy. \n\n Methods: Data on incidence were obtained from the Italian Association of Tumour Registries while mortality data were obtained from the Italian National Institute of Statistics. \n\n Results: A progressive increase of incidence with age was seen for extra-hepatic, intra-hepatic and not otherwise specified cholangiocarcinoma. Crude incidence rates were higher for extra-hepatic cholangiocarcinoma than those for intra-hepatic cholangiocarcinoma and in men compared to women. An increasing incidence trend was observed, from 1988 to 2005, for both extra-hepatic- and intra-hepatic cholangiocarcinoma with a 3-6% yearly increase and with a rate of increase higher for men than for women and for intra-hepatic- than for extra-hepatic cholangiocarcinoma. For intra-hepatic cholangiocarcinoma, the mortality rates progressively increased from 0.15 per million in 1980 to 5.9 per million in 2003, when mortality for this cancer surpassed extra-hepatic cholangiocarcinoma. Mortality rates for extra-hepatic cholangiocarcinoma showed an increasing trend from 1980 to 1994 but, in contrast to intra-hepatic cholangiocarcinoma, a stable or slightly decreasing trend from 1995 to 2003 was observed. \n\n Conclusions: In Italy, cholangiocarcinoma showed a progressive increase in incidence and mortality in the last two decades mainly in intra-hepatic cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"long term impact fibrates primary sclerosing cholangitis incomplete biochemical response ursodeoxycholic acid french spanish experience background patients primary sclerosing cholangitis psc ursodeoxycholic acid udca improves serum livers tests surrogate markers prognosis absence medical treatment proven efficacy udca widely used european psc patients however newer therapies obvi ously needed fibrates ppar agonists exert anti inflamma tory properties several experimental models autoimmunity seem beneficial effect liver biochemistries pri mary biliary cirrhosis 2014 reported improvement liver tests fibrates 15 french psc patients incomplete biochemical response udca aim confirm safety efficacy fibrates extended psc popu lation including patients another center methods retrospective study included patients psc treated fibrates fenofibrate 200mg d bezafibrate 400mg d least 6 months addition udca incomplete biochemical response alp 1uln udca 15 20mg kg d least 1 year patients associated liver diseases espe cially auto immune hepatitis included changes bio chemical parameters assessed using linear mixed model wilcoxon tests results 26 patients included 19 paris 7 barcelona 17 males median age 49 7 years 16 inflammatory bowel disease median liver stiffness 10 6 kpa corresponding fibrosis f3 median duration treatment fibrates 36 8 months 6 7 61 3 treatment fibrates alp alt decreased significantly p 0 04 0 01 respectively decrease maintained 48 months treatment ggt tended decrease p 0 10 ast total bilirubin albumin remained unchanged serious adverse event related fibrates occured 54 patients treatment fibrates stopped various reasons development biliary stones gastro intestinal bleeding decision cardiologist liver tests worsening excluding latter group interruption fibrates followed significant increase alp follow median duration 4 1 years 2 cholangiocarcinoma 5 liver transplantations 1 death recorded interestingly despite biochemical improvement liver stiffness assessed transient elastography increased significantly fibrates conclusion addition fibrates induces significant biochem ical improvement psc patients incomplete biochemical response udca seems insufficient control progression advanced psc raises critical issue surrogate markers prognosis psc clinical trials google scholar","probabilities":0.9799733,"Title":"Long Term Impact Of Fibrates In Primary Sclerosing Cholangitis With Incomplete Biochemical Response To Ursodeoxycholic Acid : The French-Spanish Experience","Abstract":"Background : In patients with primary sclerosing cholangitis (PSC), ursodeoxycholic acid (UDCA) improves serum livers tests and some surrogate markers of prognosis. In the absence of medical treatment with proven efficacy, UDCA is widely used in European PSC patients. However, newer therapies are obvi-ously needed. Fibrates, PPAR agonists that exert anti-inflamma-tory properties in several experimental models of autoimmunity, seem to have a beneficial effect on liver biochemistries in pri-mary biliary cirrhosis. In 2014, we reported improvement of liver tests under fibrates in 15 French PSC patients with an incomplete biochemical response to UDCA. Aim : To confirm the safety and efficacy of fibrates in an extended PSC popu-lation including patients from another center. Methods : This retrospective study included patients with PSC treated with fibrates (fenofibrate 200mg/d or bezafibrate 400mg/d) for at least 6 months in addition to UDCA, after an incomplete biochemical response (ALP>1ULN) to UDCA (15-20mg/kg/d) for at least 1 year. Patients with associated liver diseases, espe-cially auto-immune hepatitis were not included. Changes in bio-chemical parameters have been assessed using a linear mixed model and Wilcoxon tests. Results : 26 patients were included (19 from Paris and 7 from Barcelona) : 17 males, median age 49.7 years, 16 with inflammatory bowel disease, median liver stiffness 10.6 kPa (corresponding to fibrosis ≥ F3). Median duration of treatment with fibrates was 36.8 months (6.7-61.3). Under treatment with fibrates, ALP and ALT decreased significantly (p= 0.04 and 0.01 respectively) and this decrease was maintained at 48 months of treatment. GGT tended to decrease (p=0.10). AST, total bilirubin and albumin remained unchanged. No serious adverse event related to fibrates occured. In 54% of patients, treatment by fibrates was stopped because of various reasons : development of biliary stones, gastro-intestinal bleeding, decision by cardiologist, liver tests worsening. Excluding this latter group, interruption of fibrates was followed by a significant increase of ALP. During follow-up of a median duration of 4.1 years, 2 cholangiocarcinoma, 5 liver transplantations and 1 death were recorded. Interestingly, despite a biochemical improvement, liver stiffness assessed by transient elastography increased significantly under fibrates. Conclusion : Addition of fibrates induces a significant biochem-ical improvement in PSC patients with incomplete biochemical response to UDCA but seems to be insufficient to control the progression of advanced PSC. This raises again the critical issue of surrogate markers of prognosis in PSC clinical trials.","Source":"Google Scholar","category":"HUMAN","training_data":"Long Term Impact Of Fibrates In Primary Sclerosing Cholangitis With Incomplete Biochemical Response To Ursodeoxycholic Acid : The French-Spanish Experience Background : In patients with primary sclerosing cholangitis (PSC), ursodeoxycholic acid (UDCA) improves serum livers tests and some surrogate markers of prognosis. In the absence of medical treatment with proven efficacy, UDCA is widely used in European PSC patients. However, newer therapies are obvi-ously needed. Fibrates, PPAR agonists that exert anti-inflamma-tory properties in several experimental models of autoimmunity, seem to have a beneficial effect on liver biochemistries in pri-mary biliary cirrhosis. In 2014, we reported improvement of liver tests under fibrates in 15 French PSC patients with an incomplete biochemical response to UDCA. Aim : To confirm the safety and efficacy of fibrates in an extended PSC popu-lation including patients from another center. Methods : This retrospective study included patients with PSC treated with fibrates (fenofibrate 200mg/d or bezafibrate 400mg/d) for at least 6 months in addition to UDCA, after an incomplete biochemical response (ALP>1ULN) to UDCA (15-20mg/kg/d) for at least 1 year. Patients with associated liver diseases, espe-cially auto-immune hepatitis were not included. Changes in bio-chemical parameters have been assessed using a linear mixed model and Wilcoxon tests. Results : 26 patients were included (19 from Paris and 7 from Barcelona) : 17 males, median age 49.7 years, 16 with inflammatory bowel disease, median liver stiffness 10.6 kPa (corresponding to fibrosis ≥ F3). Median duration of treatment with fibrates was 36.8 months (6.7-61.3). Under treatment with fibrates, ALP and ALT decreased significantly (p= 0.04 and 0.01 respectively) and this decrease was maintained at 48 months of treatment. GGT tended to decrease (p=0.10). AST, total bilirubin and albumin remained unchanged. No serious adverse event related to fibrates occured. In 54% of patients, treatment by fibrates was stopped because of various reasons : development of biliary stones, gastro-intestinal bleeding, decision by cardiologist, liver tests worsening. Excluding this latter group, interruption of fibrates was followed by a significant increase of ALP. During follow-up of a median duration of 4.1 years, 2 cholangiocarcinoma, 5 liver transplantations and 1 death were recorded. Interestingly, despite a biochemical improvement, liver stiffness assessed by transient elastography increased significantly under fibrates. Conclusion : Addition of fibrates induces a significant biochem-ical improvement in PSC patients with incomplete biochemical response to UDCA but seems to be insufficient to control the progression of advanced PSC. This raises again the critical issue of surrogate markers of prognosis in PSC clinical trials. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinical presentation diagnosis staging cholangiocarcinoma cholangiocarcinoma cca heterogeneous group tumours derived cells biliary tree represent second frequent primary liver tumour according recent classifications cca subdivided intrahepatic icca extrahepatic ecca include perihilar pcca distal dcca cca cca usually identified advanced stages primary tumour grows enough produce large liver mass jaundice developed biliary tree obstruction ongoing challenges identification risk factors definition specific population higher risk developing cca main challenges development screening programs therefore late diagnosis remains unresolved issue cca imaging plays important role detection characterization cca helping radiological diagnosis guiding biopsy procedures allowing staging tumour review focuses clinical presentations diagnosis staging techniques cca pubmed","probabilities":0.9799733,"Title":"Clinical presentation, diagnosis and staging of cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a heterogeneous group of tumours, derived from cells of the biliary tree, which represent the second most frequent primary liver tumour. According to the most recent classifications, CCA can be subdivided into intrahepatic (iCCA) and extrahepatic (eCCA) which include perihilar (pCCA) and distal (dCCA) CCA. CCA are usually identified at advanced stages, when the primary tumour grows enough to produce a large liver mass or when jaundice has developed because of biliary tree obstruction. The ongoing challenges in the identification of risk factors and definition of a specific population at higher risk of developing CCA are the main challenges for the development of screening programs. Therefore, late diagnosis remains an unresolved issue in CCA. Imaging plays an important role in the detection and characterization of CCA, helping with radiological diagnosis, guiding biopsy procedures and allowing staging of the tumour. This review focuses on clinical presentations and diagnosis and staging techniques of CCA.","Source":"PubMed","category":"HUMAN","training_data":"Clinical presentation, diagnosis and staging of cholangiocarcinoma Cholangiocarcinoma (CCA) is a heterogeneous group of tumours, derived from cells of the biliary tree, which represent the second most frequent primary liver tumour. According to the most recent classifications, CCA can be subdivided into intrahepatic (iCCA) and extrahepatic (eCCA) which include perihilar (pCCA) and distal (dCCA) CCA. CCA are usually identified at advanced stages, when the primary tumour grows enough to produce a large liver mass or when jaundice has developed because of biliary tree obstruction. The ongoing challenges in the identification of risk factors and definition of a specific population at higher risk of developing CCA are the main challenges for the development of screening programs. Therefore, late diagnosis remains an unresolved issue in CCA. Imaging plays an important role in the detection and characterization of CCA, helping with radiological diagnosis, guiding biopsy procedures and allowing staging of the tumour. This review focuses on clinical presentations and diagnosis and staging techniques of CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association liver directed local therapy overall survival adults metastatic intrahepatic cholangiocarcinoma importance intrahepatic cholangiocarcinoma aggressive hepatobiliary malignant neoplasm characterized local progression frequent metastasis definitive local therapy liver setting metastatic intrahepatic cholangiocarcinoma may improve overall survival objective compare overall survival patients metastatic intrahepatic cholangiocarcinoma treated chemotherapy alone vs chemotherapy definitive liver directed local therapy design setting participants cohort study used national cancer database identify 2201 patients metastatic intrahepatic cholangiocarcinoma diagnosed january 2004 december 2014 received chemotherapy without hepatic surgery external beam radiation dose 45 gy higher multiple imputation cox proportional hazards propensity score matching landmark analysis used adjust confounding variables analyses performed september 2018 february 2019 exposures chemotherapy alone chemotherapy liver directed surgery radiation main outcomes measures overall survival results total 2201 patients 1131 51 4 male median interquartile range age 63 55 71 years received chemotherapy alone 2097 95 3 chemotherapy liver directed local therapy total 104 4 7 surgery 76 73 1 radiation 28 26 9 identified patients treated chemotherapy alone larger median interquartile range primary tumor size 7 0 4 4 10 0 cm vs 5 6 4 0 8 3 cm p 048 higher frequency lung metastases 383 25 9 vs 7 6 7 p 004 patients treated liver directed local therapy higher frequency distant lymph node metastases 34 32 7 vs 528 25 2 p 045 liver directed local therapy associated higher overall survival compared chemotherapy alone multivariable analysis hazard ratio hr 0 60 95 ci 0 48 0 74 p 001 total 208 patients treated chemotherapy alone propensity score matched 104 patients treated chemotherapy plus liver directed local therapy liver directed local therapy continued associated higher overall survival hr 0 57 95 ci 0 44 0 74 p 001 persisted landmark analysis 3 months hr 0 61 95 ci 0 47 0 79 log rank p 001 6 months hr 0 68 95 ci 0 50 0 92 log rank p 01 12 months hr 0 68 95 ci 0 47 0 98 log rank p 04 conclusions relevance study addition hepatic surgery irradiation chemotherapy associated higher overall survival compared chemotherapy alone patients metastatic intrahepatic cholangiocarcinoma findings may valuable given paucity available data disease validated independent cohort prospective study stn","probabilities":0.9799733,"Title":"Association Of Liver-Directed Local Therapy With Overall Survival In Adults With Metastatic Intrahepatic Cholangiocarcinoma","Abstract":"Importance: Intrahepatic cholangiocarcinoma is an aggressive hepatobiliary malignant neoplasm characterized by local progression and frequent metastasis. Definitive local therapy to the liver in the setting of metastatic intrahepatic cholangiocarcinoma may improve overall survival. \n\n Objective: To compare the overall survival of patients with metastatic intrahepatic cholangiocarcinoma treated with chemotherapy alone vs chemotherapy with definitive liver-directed local therapy. \n\n Design, setting, and participants: This cohort study used the National Cancer Database to identify 2201 patients with metastatic intrahepatic cholangiocarcinoma diagnosed between January 2004 and December 2014 who received chemotherapy with or without hepatic surgery or external beam radiation to a dose 45 Gy or higher. Multiple imputation, Cox proportional hazards, propensity score matching, and landmark analysis were used to adjust for confounding variables. Analyses were performed between September 2018 and February 2019. \n\n Exposures: Chemotherapy alone and chemotherapy with liver-directed surgery or radiation. \n\n Main outcomes and measures: Overall survival. \n\n Results: A total of 2201 patients (1131 [51.4%] male; median [interquartile range] age, 63 [55-71] years) who received chemotherapy alone (2097 [95.3%]) or chemotherapy with liver-directed local therapy (total, 104 [4.7%]; surgery, 76 [73.1%]; radiation, 28 [26.9%]) were identified. Patients treated with chemotherapy alone had larger median (interquartile range) primary tumor size (7.0 [4.4-10.0] cm vs 5.6 [4.0-8.3] cm; P = .048) and higher frequency of lung metastases (383 [25.9%] vs 7 [6.7%]; P = .004). Patients treated with liver-directed local therapy had higher frequency of distant lymph node metastases (34 [32.7%] vs 528 [25.2%]; P = .045). Liver-directed local therapy was associated with higher overall survival compared with chemotherapy alone on multivariable analysis (hazard ratio [HR], 0.60; 95% CI, 0.48-0.74; P < .001). A total of 208 patients treated with chemotherapy alone were propensity score matched with 104 patients treated with chemotherapy plus liver-directed local therapy. Liver-directed local therapy continued to be associated with higher overall survival (HR, 0.57; 95% CI, 0.44-0.74; P < .001), which persisted on landmark analysis at 3 months (HR, 0.61; 95% CI, 0.47-0.79; log-rank P < .001), 6 months (HR, 0.68; 95% CI, 0.50-0.92; log-rank P = .01), and 12 months (HR, 0.68; 95% CI, 0.47-0.98; log-rank P = .04). \n\n Conclusions and relevance: In this study, the addition of hepatic surgery or irradiation to chemotherapy was associated with higher overall survival when compared with chemotherapy alone in patients with metastatic intrahepatic cholangiocarcinoma. These findings may be valuable given the paucity of available data for this disease and should be validated in an independent cohort or prospective study.","Source":"STN","category":"HUMAN","training_data":"Association Of Liver-Directed Local Therapy With Overall Survival In Adults With Metastatic Intrahepatic Cholangiocarcinoma Importance: Intrahepatic cholangiocarcinoma is an aggressive hepatobiliary malignant neoplasm characterized by local progression and frequent metastasis. Definitive local therapy to the liver in the setting of metastatic intrahepatic cholangiocarcinoma may improve overall survival. \n\n Objective: To compare the overall survival of patients with metastatic intrahepatic cholangiocarcinoma treated with chemotherapy alone vs chemotherapy with definitive liver-directed local therapy. \n\n Design, setting, and participants: This cohort study used the National Cancer Database to identify 2201 patients with metastatic intrahepatic cholangiocarcinoma diagnosed between January 2004 and December 2014 who received chemotherapy with or without hepatic surgery or external beam radiation to a dose 45 Gy or higher. Multiple imputation, Cox proportional hazards, propensity score matching, and landmark analysis were used to adjust for confounding variables. Analyses were performed between September 2018 and February 2019. \n\n Exposures: Chemotherapy alone and chemotherapy with liver-directed surgery or radiation. \n\n Main outcomes and measures: Overall survival. \n\n Results: A total of 2201 patients (1131 [51.4%] male; median [interquartile range] age, 63 [55-71] years) who received chemotherapy alone (2097 [95.3%]) or chemotherapy with liver-directed local therapy (total, 104 [4.7%]; surgery, 76 [73.1%]; radiation, 28 [26.9%]) were identified. Patients treated with chemotherapy alone had larger median (interquartile range) primary tumor size (7.0 [4.4-10.0] cm vs 5.6 [4.0-8.3] cm; P = .048) and higher frequency of lung metastases (383 [25.9%] vs 7 [6.7%]; P = .004). Patients treated with liver-directed local therapy had higher frequency of distant lymph node metastases (34 [32.7%] vs 528 [25.2%]; P = .045). Liver-directed local therapy was associated with higher overall survival compared with chemotherapy alone on multivariable analysis (hazard ratio [HR], 0.60; 95% CI, 0.48-0.74; P < .001). A total of 208 patients treated with chemotherapy alone were propensity score matched with 104 patients treated with chemotherapy plus liver-directed local therapy. Liver-directed local therapy continued to be associated with higher overall survival (HR, 0.57; 95% CI, 0.44-0.74; P < .001), which persisted on landmark analysis at 3 months (HR, 0.61; 95% CI, 0.47-0.79; log-rank P < .001), 6 months (HR, 0.68; 95% CI, 0.50-0.92; log-rank P = .01), and 12 months (HR, 0.68; 95% CI, 0.47-0.98; log-rank P = .04). \n\n Conclusions and relevance: In this study, the addition of hepatic surgery or irradiation to chemotherapy was associated with higher overall survival when compared with chemotherapy alone in patients with metastatic intrahepatic cholangiocarcinoma. These findings may be valuable given the paucity of available data for this disease and should be validated in an independent cohort or prospective study. STN","prediction_labels":"HUMAN"},{"cleaned":"value e pass models predicting postoperative morbidity mortality resection perihilar cholangiocarcinoma gallbladder carcinoma background previously reported general risk model estimation physiologic ability surgical stress e pass modified version pass high predictive power postoperative mortality morbidity variety gastrointestinal surgeries study evaluated utilities proximal biliary carcinoma resection methods e pass variables collected patients undergoing resection perihilar cholangiocarcinoma gallbladder carcinoma japanese referral hospitals results analysis 125 patients gallbladder cancer 97 patients perihilar cholangiocarcinoma n 222 fifty six patients 25 underwent liver resection either hemihepatectomy extended hemihepatectomy e pass models showed high discrimination power predict hospital mortality areas receiver operating characteristic curve 95 confidence intervals 0 85 0 76 0 94 e pass 0 82 0 73 0 91 pass predicted mortality rates correlated severity postoperative complications spearman rank correlation coefficient 0 51 p 0 001 e pass 0 47 p 0 001 pass conclusions e pass models examined herein may accurately predict postoperative morbidity mortality proximal biliary carcinoma resection models useful surgical decision making informed consent risk adjustments surgical audits stn","probabilities":0.9799733,"Title":"Value Of E-Pass Models For Predicting Postoperative Morbidity And Mortality In Resection Of Perihilar Cholangiocarcinoma And Gallbladder Carcinoma","Abstract":"Background: It has previously been reported that a general risk model, Estimation of Physiologic Ability and Surgical Stress (E-PASS), and its modified version, mE-PASS, had a high predictive power for postoperative mortality and morbidity in a variety of gastrointestinal surgeries. This study evaluated their utilities in proximal biliary carcinoma resection. \r\n\r\n Methods: E-PASS variables were collected in patients undergoing resection of perihilar cholangiocarcinoma and gallbladder carcinoma in Japanese referral hospitals. \r\n\r\n Results: Analysis of 125 patients with gallbladder cancer and 97 patients with perihilar cholangiocarcinoma (n = 222). Fifty-six patients (25%) underwent liver resection with either hemihepatectomy or extended hemihepatectomy. The E-PASS models showed a high discrimination power to predict in-hospital mortality; areas under the receiver operating characteristic curve (95% confidence intervals) were 0.85 (0.76-0.94) for E-PASS and 0.82 (0.73-0.91) for mE-PASS. The predicted mortality rates correlated with the severity of postoperative complications (Spearman's rank correlation coefficient: ρ = 0.51, P < 0.001 for E-PASS; ρ = 0.47, P < 0.001 for mE-PASS). \r\n\r\n Conclusions: The E-PASS models examined herein may accurately predict postoperative morbidity and mortality in proximal biliary carcinoma resection. These models will be useful for surgical decision-making, informed consent, and risk adjustments in surgical audits.","Source":"STN","category":"HUMAN","training_data":"Value Of E-Pass Models For Predicting Postoperative Morbidity And Mortality In Resection Of Perihilar Cholangiocarcinoma And Gallbladder Carcinoma Background: It has previously been reported that a general risk model, Estimation of Physiologic Ability and Surgical Stress (E-PASS), and its modified version, mE-PASS, had a high predictive power for postoperative mortality and morbidity in a variety of gastrointestinal surgeries. This study evaluated their utilities in proximal biliary carcinoma resection. \r\n\r\n Methods: E-PASS variables were collected in patients undergoing resection of perihilar cholangiocarcinoma and gallbladder carcinoma in Japanese referral hospitals. \r\n\r\n Results: Analysis of 125 patients with gallbladder cancer and 97 patients with perihilar cholangiocarcinoma (n = 222). Fifty-six patients (25%) underwent liver resection with either hemihepatectomy or extended hemihepatectomy. The E-PASS models showed a high discrimination power to predict in-hospital mortality; areas under the receiver operating characteristic curve (95% confidence intervals) were 0.85 (0.76-0.94) for E-PASS and 0.82 (0.73-0.91) for mE-PASS. The predicted mortality rates correlated with the severity of postoperative complications (Spearman's rank correlation coefficient: ρ = 0.51, P < 0.001 for E-PASS; ρ = 0.47, P < 0.001 for mE-PASS). \r\n\r\n Conclusions: The E-PASS models examined herein may accurately predict postoperative morbidity and mortality in proximal biliary carcinoma resection. These models will be useful for surgical decision-making, informed consent, and risk adjustments in surgical audits. STN","prediction_labels":"HUMAN"},{"cleaned":"unveiling silent killer 17 year review gallbladder cancers background gallbladder cancer gbc incidence varies greatly low 0 25 0 89 western countries 2 india chile gallbladder cancer associated poor prognosis usually asymptomatic early stages cases incidentally diagnosed histopathological analysis cholecystectomy benign indications scarce data incidental gallbladder cancer diagnosis uk using current staging methods aim study review cases gallbladder cancer incidentally diagnosed 17 year period uk tertiary hospital assess mortality rates associated pathology methods consecutive series 41 cases gallbladder cancer diagnosed incidentally histopathological analysis post cholecystectomy january 2001 january 2018 single tertiary centre north midlands uk demographic surgical histopathological data retrieved local hospital database data analysis presented mean standard deviation sd percentages chi square test used assess differences mortality rate across tumour staging categories p value 0 05 considered statistically significant results mean age 69 9 years whilst 65 female commonest presentations acute cholecystitis 35 biliary colic 32 5 pancreatitis 7 5 47 5 emergency take majority laparoscopic cholecystectomies 92 5 10 liver bed resections risk factors gbc gallstones thick walled gallbladder polyps identified 82 5 45 15 cases respectively majority locally advanced disease 55 pt2 30 pt3 metastases occurring 15 one year five year survival rates 60 32 5 respectively higher mortality pt2 pt3 stages one year p 0 028 five year p 0 015 conclusions study provides significant evidence clinical histopathological factors associated incidental gallbladder cancer diagnosis uk study also reinforces concept gallbladder cancer gbc mostly diagnosed later stages disease picked post cholecystectomy incidental disease mortality rates associated gallbladder cancer high directly correlate tumour staging therefore highlight importance histopathological examination gallbladder specimen post cholecystectomy google scholar","probabilities":0.9799733,"Title":"Unveiling A Silent Killer: A 17-Year Review Of Gallbladder Cancers","Abstract":"Background: Gallbladder cancer (GBC) incidence varies greatly, from as low\nas 0.25-0.89% in Western countries up to 2% in India or Chile. Gallbladder\ncancer is associated with poor prognosis as it is usually asymptomatic in early\nstages. Most cases are now incidentally diagnosed by histopathological analysis\nafter cholecystectomy for benign indications. There is scarce data on incidental\ngallbladder cancer diagnosis in the UK using current staging methods. The\naim of this study was to review all cases of gallbladder cancer incidentally\ndiagnosed over a 17-year period in a UK tertiary hospital and assess mortality\nrates associated with this pathology.\nMethods: A consecutive series of 41 cases of gallbladder cancer diagnosed\nincidentally by histopathological analysis post-cholecystectomy between January\n2001 and January 2018 at a single tertiary centre in the North midlands\n(UK). Demographic, surgical, and histopathological data were retrieved from\nthe local hospital database. The data analysis is presented as mean and standard\ndeviation (±SD) or percentages. Chi-square test was used to assess differences in\nmortality rate across tumour staging categories. A p value<0.05 was considered\nstatistically significant.\nResults: The mean age was 69(±9) years whilst 65% were female. The\ncommonest presentations were acute cholecystitis (35%), biliary colic (32.5%)\nand pancreatitis (7.5%) with 47.5% through emergency take. Majority had\nlaparoscopic cholecystectomies (92.5%) with 10% having liver bed resections.\nRisk factors for GBC such as gallstones, thick-walled gallbladder, and polyps\nwere identified in 82.5%, 45%, and 15% of cases, respectively. Majority had\nlocally advanced disease (55% pT2; 30% pT3), with metastases occurring in\n15%. One-year and five-year survival rates were 60% and 32.5%, respectively,\nwith higher mortality in pT2/pT3 stages at one-year (p=0.028) and five-year\n(p=0.015).\nConclusions: Our study provides significant evidence on clinical and\nhistopathological factors associated with incidental gallbladder cancer diagnosis\nin UK. This study also reinforces the concept that gallbladder cancer (GBC) is\nmostly diagnosed at later stages of the disease and are picked up post cholecystectomy\nas incidental disease. Mortality rates associated with gallbladder cancer\nare high and directly correlate with tumour staging. Therefore, we highlight\nthe importance of histopathological examination of gallbladder specimen\npost-cholecystectomy.","Source":"Google Scholar","category":"HUMAN","training_data":"Unveiling A Silent Killer: A 17-Year Review Of Gallbladder Cancers Background: Gallbladder cancer (GBC) incidence varies greatly, from as low\nas 0.25-0.89% in Western countries up to 2% in India or Chile. Gallbladder\ncancer is associated with poor prognosis as it is usually asymptomatic in early\nstages. Most cases are now incidentally diagnosed by histopathological analysis\nafter cholecystectomy for benign indications. There is scarce data on incidental\ngallbladder cancer diagnosis in the UK using current staging methods. The\naim of this study was to review all cases of gallbladder cancer incidentally\ndiagnosed over a 17-year period in a UK tertiary hospital and assess mortality\nrates associated with this pathology.\nMethods: A consecutive series of 41 cases of gallbladder cancer diagnosed\nincidentally by histopathological analysis post-cholecystectomy between January\n2001 and January 2018 at a single tertiary centre in the North midlands\n(UK). Demographic, surgical, and histopathological data were retrieved from\nthe local hospital database. The data analysis is presented as mean and standard\ndeviation (±SD) or percentages. Chi-square test was used to assess differences in\nmortality rate across tumour staging categories. A p value<0.05 was considered\nstatistically significant.\nResults: The mean age was 69(±9) years whilst 65% were female. The\ncommonest presentations were acute cholecystitis (35%), biliary colic (32.5%)\nand pancreatitis (7.5%) with 47.5% through emergency take. Majority had\nlaparoscopic cholecystectomies (92.5%) with 10% having liver bed resections.\nRisk factors for GBC such as gallstones, thick-walled gallbladder, and polyps\nwere identified in 82.5%, 45%, and 15% of cases, respectively. Majority had\nlocally advanced disease (55% pT2; 30% pT3), with metastases occurring in\n15%. One-year and five-year survival rates were 60% and 32.5%, respectively,\nwith higher mortality in pT2/pT3 stages at one-year (p=0.028) and five-year\n(p=0.015).\nConclusions: Our study provides significant evidence on clinical and\nhistopathological factors associated with incidental gallbladder cancer diagnosis\nin UK. This study also reinforces the concept that gallbladder cancer (GBC) is\nmostly diagnosed at later stages of the disease and are picked up post cholecystectomy\nas incidental disease. Mortality rates associated with gallbladder cancer\nare high and directly correlate with tumour staging. Therefore, we highlight\nthe importance of histopathological examination of gallbladder specimen\npost-cholecystectomy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"increased risk malignant neoplasms among patients cirrhosis background aims clear cirrhosis affects risks hepatocellular carcinoma hcc non hcc cancers rare among patients assessed risk malignant neoplasms patients cirrhosis methods patients diagnosed cirrhosis gothenburg sweden 1994 2005 identified linked national cancer death registers studied data 1019 patients cirrhosis 68 men 48 alcoholic liver disease ald 10 hepatitis c virus hcv 12 hcv ald standardized incidence ratios malignant neoplasms calculated corrected sex age calendar year according data general swedish population follow period 3290 person years results overall 114 11 patients developed hcc hcc occurred frequently among patients hcv diseases p 05 hcc risk differ among patients hcv without ald p 05 compared general population cirrhotic patients increased risk hcc 26 fold cholangiocarcinoma 13 fold esophageal 8 fold pancreatic 5 fold colorectal lung cancers 4 fold risk cholangiocarcinoma increased mainly among patients non ald cirrhosis whereas risk extrahepatic malignancies increased mainly among patients ald cirrhosis conclusions overall risk non hcc malignancies 2 fold greater patients cirrhosis mostly biliary gastrointestinal malignancies general population risk non hcc cancers differs patients ald non ald cirrhosis increased risk hcc among patients cirrhosis associated hcv among patients hcv without ald pubmed","probabilities":0.9799733,"Title":"Increased risk for malignant neoplasms among patients with cirrhosis","Abstract":"BACKGROUND & AIMS: It is not clear how cirrhosis affects the risks for hepatocellular carcinoma (HCC) and non-HCC cancers, which are rare among these patients. We assessed the risk for malignant neoplasms in patients with cirrhosis. METHODS: Patients diagnosed with cirrhosis in Gothenburg, Sweden, from 1994 to 2005 were identified and linked to the National Cancer and Death registers. We studied data from 1019 patients with cirrhosis: 68% men, 48% with alcoholic liver disease (ALD), 10% with hepatitis C virus (HCV), and 12% with HCV + ALD. Standardized incidence ratios for malignant neoplasms were calculated (corrected for sex, age, and calendar year according to data from the general Swedish population). The follow-up period was 3290 person-years. RESULTS: Overall, 114 (11%) patients developed HCC; HCC occurred more frequently among patients with HCV than other diseases (P < .05). HCC risk did not differ among patients with HCV, with or without ALD (P > .05). Compared with the general population, cirrhotic patients had increased risk for HCC (26-fold); cholangiocarcinoma (13-fold); and esophageal (8-fold), pancreatic (5-fold), and colorectal and lung cancers (each 4-fold). The risk for cholangiocarcinoma increased mainly among patients with non-ALD cirrhosis, whereas the risk for extrahepatic malignancies increased mainly among patients with ALD and cirrhosis. CONCLUSIONS: The overall risk for non-HCC malignancies is more than 2-fold greater for patients with cirrhosis (mostly in biliary and gastrointestinal malignancies) than of the general population. The risk for non-HCC cancers differs between patients with ALD and non-ALD cirrhosis. The increased risk for HCC among patients with cirrhosis is associated with HCV; it is the same among patients with HCV, with or without ALD.","Source":"PubMed","category":"HUMAN","training_data":"Increased risk for malignant neoplasms among patients with cirrhosis BACKGROUND & AIMS: It is not clear how cirrhosis affects the risks for hepatocellular carcinoma (HCC) and non-HCC cancers, which are rare among these patients. We assessed the risk for malignant neoplasms in patients with cirrhosis. METHODS: Patients diagnosed with cirrhosis in Gothenburg, Sweden, from 1994 to 2005 were identified and linked to the National Cancer and Death registers. We studied data from 1019 patients with cirrhosis: 68% men, 48% with alcoholic liver disease (ALD), 10% with hepatitis C virus (HCV), and 12% with HCV + ALD. Standardized incidence ratios for malignant neoplasms were calculated (corrected for sex, age, and calendar year according to data from the general Swedish population). The follow-up period was 3290 person-years. RESULTS: Overall, 114 (11%) patients developed HCC; HCC occurred more frequently among patients with HCV than other diseases (P < .05). HCC risk did not differ among patients with HCV, with or without ALD (P > .05). Compared with the general population, cirrhotic patients had increased risk for HCC (26-fold); cholangiocarcinoma (13-fold); and esophageal (8-fold), pancreatic (5-fold), and colorectal and lung cancers (each 4-fold). The risk for cholangiocarcinoma increased mainly among patients with non-ALD cirrhosis, whereas the risk for extrahepatic malignancies increased mainly among patients with ALD and cirrhosis. CONCLUSIONS: The overall risk for non-HCC malignancies is more than 2-fold greater for patients with cirrhosis (mostly in biliary and gastrointestinal malignancies) than of the general population. The risk for non-HCC cancers differs between patients with ALD and non-ALD cirrhosis. The increased risk for HCC among patients with cirrhosis is associated with HCV; it is the same among patients with HCV, with or without ALD. PubMed","prediction_labels":"HUMAN"},{"cleaned":"new nomogram predicting overall survival patients intrahepatic cholangiocarcinoma getting copy pasted properly go link google scholar","probabilities":0.9799733,"Title":"A New Nomogram Predicting Overall Survival Of Patients With Intrahepatic Cholangiocarcinoma","Abstract":"Not getting copy pasted properly. Go through the link","Source":"Google Scholar","category":"HUMAN","training_data":"A New Nomogram Predicting Overall Survival Of Patients With Intrahepatic Cholangiocarcinoma Not getting copy pasted properly. Go through the link Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"survival patients distal cholangiocarcinoma population based dutch cohort introduction real life treatment outcomes distal cholangiocarcinoma western world largely unknown study investigated treatment outcomes time trends predictors survival nationwide cohort patients distal cholangiocarcinoma aims methods population based cohort derived netherlands cancer registry studied patients resected unresected registered distal cholangiocarcinoma 2009 2015 included missing data handled using multiple imputation survival predictors survival analyzed using kaplan meier cox regression analysis backward selection results study period 1152 patients registered 537 46 6 underwent resection 376 32 6 unresected non metastasized disease m0 239 20 7 metastasized disease m1 resected group 30 day mortality 5 4 n 29 adjuvant chemotherapy rarely used 8 4 n 45 palliative chemotherapy administered 19 5 1 patients non resected m0 74 31 0 m1 tumors median overall survival patients resected unresected m0 m1 tumors 23 months 95 ci 20 25 7 months 95 ci 6 8 4 months 95 ci 3 5 p50 001 respectively time survival improve subgroups negative independent prognostic factors survival resected patients increasing age p 0 01 t3 t4 stage p 0 02 higher lymph node ratio p50 001 poor differentiation p50 001 microscopic p50 001 macroscopic p 0 03 residual disease conclusion largest nationwide western study distal cholangiocarcinoma demonstrates 47 resection rate acceptable survival despite limited use adjuvant chemotherapy poor survival limited use chemotherapy unresected patients study identified predictors survival useful stratify future clinical trials neo adjuvant palliative treatment google scholar","probabilities":0.9799733,"Title":"Survival Of Patients With Distal Cholangiocarcinoma: A Population-Based Dutch Cohort","Abstract":"Introduction: Real-life treatment and outcomes of distal cholangiocarcinoma in the Western world are largely unknown. This study investigated treatment, outcomes, time trends and predictors for survival in a nationwide cohort of patients with distal cholangiocarcinoma. Aims and Methods: A population-based cohort derived from the Netherlands Cancer Registry was studied. All patients (resected and unresected) registered to have distal cholangiocarcinoma between 2009–2015 were included. Missing data were handled using multiple imputation. Survival and predictors for survival were analyzed using Kaplan Meier and Cox regression analysis (backward selection). Results: During the study period, 1152 patients were registered; 537 (46.6%) underwent resection, 376 (32.6%) had unresected non-metastasized disease (M0) and 239 (20.7%) had metastasized disease (M1). In the resected group, 30-day mortality was 5.4% (n¼29) and adjuvant chemotherapy was rarely used (8.4%, n¼45). Palliative chemotherapy was administered in 19 (5.1%) of the patients with non-resected M0 and in 74 (31.0%) of the M1 tumors. Median overall survival for patients with resected, unresected M0, and M1 tumors was 23 months (95% CI 20–25), 7 months (95% CI 6–8) and 4 months (95% CI 3–5) (p50.001), respectively. Over time, survival did not improve in any of the subgroups. Negative independent prognostic factors for survival in resected patients were increasing age (p¼0.01), T3/T4 stage (p¼0.02), higher lymph node ratio (p50.001), poor differentiation (p50.001), and microscopic (p50.001) or macroscopic (p¼0.03) residual disease. Conclusion: This largest nationwide Western study on distal cholangiocarcinoma demonstrates a 47% resection rate with acceptable survival despite limited use of adjuvant chemotherapy, and poor survival and limited use of chemotherapy in unresected patients. The study identified predictors for survival which can be useful to stratify future clinical trials with (neo-) adjuvant or palliative treatment.","Source":"Google Scholar","category":"HUMAN","training_data":"Survival Of Patients With Distal Cholangiocarcinoma: A Population-Based Dutch Cohort Introduction: Real-life treatment and outcomes of distal cholangiocarcinoma in the Western world are largely unknown. This study investigated treatment, outcomes, time trends and predictors for survival in a nationwide cohort of patients with distal cholangiocarcinoma. Aims and Methods: A population-based cohort derived from the Netherlands Cancer Registry was studied. All patients (resected and unresected) registered to have distal cholangiocarcinoma between 2009–2015 were included. Missing data were handled using multiple imputation. Survival and predictors for survival were analyzed using Kaplan Meier and Cox regression analysis (backward selection). Results: During the study period, 1152 patients were registered; 537 (46.6%) underwent resection, 376 (32.6%) had unresected non-metastasized disease (M0) and 239 (20.7%) had metastasized disease (M1). In the resected group, 30-day mortality was 5.4% (n¼29) and adjuvant chemotherapy was rarely used (8.4%, n¼45). Palliative chemotherapy was administered in 19 (5.1%) of the patients with non-resected M0 and in 74 (31.0%) of the M1 tumors. Median overall survival for patients with resected, unresected M0, and M1 tumors was 23 months (95% CI 20–25), 7 months (95% CI 6–8) and 4 months (95% CI 3–5) (p50.001), respectively. Over time, survival did not improve in any of the subgroups. Negative independent prognostic factors for survival in resected patients were increasing age (p¼0.01), T3/T4 stage (p¼0.02), higher lymph node ratio (p50.001), poor differentiation (p50.001), and microscopic (p50.001) or macroscopic (p¼0.03) residual disease. Conclusion: This largest nationwide Western study on distal cholangiocarcinoma demonstrates a 47% resection rate with acceptable survival despite limited use of adjuvant chemotherapy, and poor survival and limited use of chemotherapy in unresected patients. The study identified predictors for survival which can be useful to stratify future clinical trials with (neo-) adjuvant or palliative treatment. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"evaluation extra capsular lymph node involvement patients extra hepatic bile duct cancer background lymph node metastasis one important prognostic factors extra hepatic bile duct carcinoma exhbdc extra capsular lymph node involvement exclni extension cancer cells nodal capsule perinodal fatty tissue prognostic impact exclni shown significant mainly head neck malignancies recently prognostic impacts exclni evaluated gastrointestinal malignancies however data available regarding incidence prognostic significance extra capsular lymph node involvement exclni resectable exhbdcs aim present study first evaluate incidence exclni surgically treated exhbdcs second determine prognostic impact exclni patients surgically treated exhbdcs methods total 228 patients 110 cases hilar cholangiocarcinoma 118 cases distal cholangiocarcinoma surgically treated exhbdcs included retrospective study exclni defined extension cancer cells nodal capsule perinodal fatty tissue existence exclni prognostic value analyzed subgroup lymph node metastasis results exclni detected 22 patients lymph node metastasis surgically treated exhbdc presence exclni correlated distal cholangiocarcinoma p 0 002 univariate analysis survival perineural invasion vascular invasion histological grade lymph node metastasis statistically significant factors multivariate analysis lymph node metastasis identified significant independent prognostic factor patients resectable exhbdc subgroups lymph node metastasis including presence exclni location lymph node metastasis number lymph node metastasis statistically significant impact survival conclusion exclni present 22 lnm 7 overall patients patients surgical treated exhbdcs exclni impact survival patients surgically treated exhbdcs pubmed","probabilities":0.7966102,"Title":"Evaluation of extra capsular lymph node involvement in patients with extra-hepatic bile duct cancer","Abstract":"BACKGROUND: Lymph node metastasis is one of the most important prognostic factors for extra-hepatic bile duct carcinoma (ExHBDC). Extra capsular lymph node involvement (ExCLNI) is the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The prognostic impact of ExCLNI has been shown to be significant mainly in head and neck malignancies. Recently, the prognostic impacts of ExCLNI have evaluated in gastrointestinal malignancies. However no data is available regarding the incidence and prognostic significance of extra-capsular lymph node involvement (ExCLNI) in resectable ExHBDCs. The aim of the present study is first to evaluate the incidence of ExCLNI in surgically-treated ExHBDCs and second, to determine the prognostic impact of ExCLNI in patients with surgically-treated ExHBDCs. METHODS: A total of 228 patients (110 cases of hilar cholangiocarcinoma and 118 cases of distal cholangiocarcinoma) with surgically-treated ExHBDCs were included in this retrospective study. ExCLNI was defined as the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The existence of ExCLNI and its prognostic value were analyzed as a subgroup of lymph node metastasis. RESULTS: ExCLNI was detected in only 22% of patients with lymph node metastasis of surgically-treated ExHBDC. The presence of ExCLNI correlated with distal cholangiocarcinoma (p = 0.002). On univariate analysis for survival, perineural invasion, vascular invasion, histological grade, and lymph node metastasis were statistically significant factors. On multivariate analysis, only lymph node metastasis was identified as a significant independent prognostic factor in patients with resectable ExHBDC. Subgroups of lymph node metastasis including the presence of ExCLNI, location of lymph node metastasis, and the number of lymph node metastasis had no statistically significant impact on survival. CONCLUSION: ExCLNI was present in only 22% of the LNM (7% of overall patients) in patients with surgical treated ExHBDCs. And ExCLNI would have no impact on the survival of patients with surgically-treated ExHBDCs.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of extra capsular lymph node involvement in patients with extra-hepatic bile duct cancer BACKGROUND: Lymph node metastasis is one of the most important prognostic factors for extra-hepatic bile duct carcinoma (ExHBDC). Extra capsular lymph node involvement (ExCLNI) is the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The prognostic impact of ExCLNI has been shown to be significant mainly in head and neck malignancies. Recently, the prognostic impacts of ExCLNI have evaluated in gastrointestinal malignancies. However no data is available regarding the incidence and prognostic significance of extra-capsular lymph node involvement (ExCLNI) in resectable ExHBDCs. The aim of the present study is first to evaluate the incidence of ExCLNI in surgically-treated ExHBDCs and second, to determine the prognostic impact of ExCLNI in patients with surgically-treated ExHBDCs. METHODS: A total of 228 patients (110 cases of hilar cholangiocarcinoma and 118 cases of distal cholangiocarcinoma) with surgically-treated ExHBDCs were included in this retrospective study. ExCLNI was defined as the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The existence of ExCLNI and its prognostic value were analyzed as a subgroup of lymph node metastasis. RESULTS: ExCLNI was detected in only 22% of patients with lymph node metastasis of surgically-treated ExHBDC. The presence of ExCLNI correlated with distal cholangiocarcinoma (p = 0.002). On univariate analysis for survival, perineural invasion, vascular invasion, histological grade, and lymph node metastasis were statistically significant factors. On multivariate analysis, only lymph node metastasis was identified as a significant independent prognostic factor in patients with resectable ExHBDC. Subgroups of lymph node metastasis including the presence of ExCLNI, location of lymph node metastasis, and the number of lymph node metastasis had no statistically significant impact on survival. CONCLUSION: ExCLNI was present in only 22% of the LNM (7% of overall patients) in patients with surgical treated ExHBDCs. And ExCLNI would have no impact on the survival of patients with surgically-treated ExHBDCs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extent lymphadenectomy number lymph nodes positive lymph node ratio neutrophil lymphocyte ratio impact surgical outcome perihilar cholangiocarcinoma background lymph node ln status important predictor survival following resection perihilar cholangiocarcinoma phcca controversies still exist regard prognostic value optimum extent lymphadenectomy total number nodes removed ln ratio lnr neutrophil lymphocyte ratio nlr overall survival os disease free survival dfs following phcca resection methods 1994 2010 84 phccas resected 78 included analysis kaplan meier survival curves studied using log rank statistics assess variables affected os dfs variables showed statistical significance p 0 05 kaplan meier univariate analysis subjected multivariate analysis using cox proportional hazards model results five year os node positive status n 45 10 whereas node negative n 33 os 41 p 0 001 similarly 5 year dfs worse node positive group 8 node negative group 36 p 0 001 difference 5 year os 31 vs 12 p 0 135 dfs 22 vs 16 p 0 518 regional lymphadenectomy underwent regional plus para aortic lymphadenectomy respectively univariate analysis patients 20 lns removed worse 5 year os 0 compared less 20 lns removed 29 p 0 047 moderate poor tumour differentiation distant metastasis ln involvement independent predictors os positive lnr effect os vascular invasion lnr least 0 37 independent predictors dfs nlr effect os dfs conclusion extended lymphadenectomy patients 20 lns worse os compared limited 20 lns resection lnr least 0 37 independent predictor dfs stn","probabilities":0.9799733,"Title":"Does The Extent Of Lymphadenectomy Number Of Lymph Nodes Positive Lymph Node Ratio And Neutrophil-Lymphocyte Ratio Impact Surgical Outcome Of Perihilar Cholangiocarcinoma?","Abstract":"Background: Lymph node (LN) status is an important predictor of survival following resection of perihilar cholangiocarcinoma (PHCCA). Controversies still exist with regard to the prognostic value of optimum extent of lymphadenectomy, total number of nodes removed, LN ratio (LNR) and neutrophil-lymphocyte ratio (NLR) on overall survival (OS) and disease-free survival (DFS) following PHCCA resection. \r\n\r\n Methods: From 1994 to 2010, 84 PHCCAs were resected; 78 are included in this analysis. Kaplan-Meier survival curves were studied using log-rank statistics to assess which variables affected OS and DFS. The variables that showed statistical significance (P<0.05) on Kaplan-Meier univariate analysis were subjected to multivariate analysis using Cox proportional hazards model. \r\n\r\n Results: Five-year OS for node-positive status (n=45) was 10%, whereas node-negative (n=33) OS was 41% (P<0.001). Similarly, 5-year DFS was worse in the node-positive group (8%) than in the node-negative group (36%, P=0.001). There was no difference in 5-year OS (31 vs. 12%, P=0.135) and DFS (22 vs. 16%, P=0.518) between those with regional lymphadenectomy and those who underwent regional plus para-aortic lymphadenectomy, respectively. On univariate analysis, patients with 20 or more LNs removed had worse 5-year OS (0%) when compared with those with less than 20 LNs removed (29%, P=0.047). Moderate/poor tumour differentiation, distant metastasis and LN involvement were independent predictors of OS. Positive LNR had no effect on OS. Vascular invasion and an LNR of at least 0.37 were independent predictors of DFS. NLR had no effect on OS and DFS. \r\n\r\n Conclusion: Extended lymphadenectomy patients (≥20 LNs) had worse OS when compared with those with more limited (<20 LNs) resection. An LNR of at least 0.37 is an independent predictor of DFS.","Source":"STN","category":"HUMAN","training_data":"Does The Extent Of Lymphadenectomy Number Of Lymph Nodes Positive Lymph Node Ratio And Neutrophil-Lymphocyte Ratio Impact Surgical Outcome Of Perihilar Cholangiocarcinoma? Background: Lymph node (LN) status is an important predictor of survival following resection of perihilar cholangiocarcinoma (PHCCA). Controversies still exist with regard to the prognostic value of optimum extent of lymphadenectomy, total number of nodes removed, LN ratio (LNR) and neutrophil-lymphocyte ratio (NLR) on overall survival (OS) and disease-free survival (DFS) following PHCCA resection. \r\n\r\n Methods: From 1994 to 2010, 84 PHCCAs were resected; 78 are included in this analysis. Kaplan-Meier survival curves were studied using log-rank statistics to assess which variables affected OS and DFS. The variables that showed statistical significance (P<0.05) on Kaplan-Meier univariate analysis were subjected to multivariate analysis using Cox proportional hazards model. \r\n\r\n Results: Five-year OS for node-positive status (n=45) was 10%, whereas node-negative (n=33) OS was 41% (P<0.001). Similarly, 5-year DFS was worse in the node-positive group (8%) than in the node-negative group (36%, P=0.001). There was no difference in 5-year OS (31 vs. 12%, P=0.135) and DFS (22 vs. 16%, P=0.518) between those with regional lymphadenectomy and those who underwent regional plus para-aortic lymphadenectomy, respectively. On univariate analysis, patients with 20 or more LNs removed had worse 5-year OS (0%) when compared with those with less than 20 LNs removed (29%, P=0.047). Moderate/poor tumour differentiation, distant metastasis and LN involvement were independent predictors of OS. Positive LNR had no effect on OS. Vascular invasion and an LNR of at least 0.37 were independent predictors of DFS. NLR had no effect on OS and DFS. \r\n\r\n Conclusion: Extended lymphadenectomy patients (≥20 LNs) had worse OS when compared with those with more limited (<20 LNs) resection. An LNR of at least 0.37 is an independent predictor of DFS. STN","prediction_labels":"HUMAN"},{"cleaned":"aggressive approach en bloc resection treatment klatskin tumors objective analyze results since 2007 intro duction aggressive approaches en bloc vascular extended liver resections relation safety feasi bility survival treatment hiliar chol angiocarcinoma phc patients methods july 2007 december 2014 32 consecutive patients phc underwent surgery curative intent right hepatectomy trisectionectomy performed except cases predominant left side involvement en bloc resection including portal vein bifurcation right hepa tic artery vascular reconstruction made always suspect vessel involvement imaging studies prior surgery tumor close vessels avoid tumor spread peri operative data histological findings tumor recurrence survival rates surgery registered results although 53 17 pa tients advanced stages achieved good survival 5 years 44 increase 65 patients without advanced stages morbidity 23 72 mortality 5 15 6 similar data published groups conclusions aggressive approach en bloc extended liver resections vascular reconstruction acceptable preoperative morbimortality good 5 years survival google scholar","probabilities":0.9799733,"Title":"Aggressive Approach With En Bloc Resection In The Treatment Of Klatskin Tumors","Abstract":"Objective: Analyze our results since 2007 with the intro- duction of more aggressive approaches (“en bloc”, vascular and extended liver resections) in relation to safety, feasi- bility and survival in the treatment of hiliar chol- angiocarcinoma (PHC).\nPatients and methods: From July 2007 to December 2014, 32 consecutive patients with PHC underwent surgery with curative intent. A right hepatectomy or trisectionectomy was performed except in those cases with predominant left side involvement. En bloc” resection including the portal vein bifurcation or right hepátic artery, with vascular reconstruction was made, always that we suspect vessel involvement in the imaging studies prior to surgery, or when the tumor was too close to the vessels to avoid tumor spread. Peri-operative data, histological findings, tumor recurrence and survival rates after surgery were registered. Results: Although we had more than 53% (17) of the pa- tients with advanced stages, we achieved a good survival at 5 years of 44%, that increase until 65% in those patients without advanced stages. Our morbidity 23 (72%) and mortality 5 (15,6%) was similar to data published by other groups.\nConclusions: Aggressive approach with “en bloc” and extended liver resections with vascular reconstruction has an acceptable preoperative morbimortality with a good 5 years survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Aggressive Approach With En Bloc Resection In The Treatment Of Klatskin Tumors Objective: Analyze our results since 2007 with the intro- duction of more aggressive approaches (“en bloc”, vascular and extended liver resections) in relation to safety, feasi- bility and survival in the treatment of hiliar chol- angiocarcinoma (PHC).\nPatients and methods: From July 2007 to December 2014, 32 consecutive patients with PHC underwent surgery with curative intent. A right hepatectomy or trisectionectomy was performed except in those cases with predominant left side involvement. En bloc” resection including the portal vein bifurcation or right hepátic artery, with vascular reconstruction was made, always that we suspect vessel involvement in the imaging studies prior to surgery, or when the tumor was too close to the vessels to avoid tumor spread. Peri-operative data, histological findings, tumor recurrence and survival rates after surgery were registered. Results: Although we had more than 53% (17) of the pa- tients with advanced stages, we achieved a good survival at 5 years of 44%, that increase until 65% in those patients without advanced stages. Our morbidity 23 (72%) and mortality 5 (15,6%) was similar to data published by other groups.\nConclusions: Aggressive approach with “en bloc” and extended liver resections with vascular reconstruction has an acceptable preoperative morbimortality with a good 5 years survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"trends incidence management biliary tract cancer french population based study background aims trends incidence management biliary tract cancer btc investigated well defined french population 30 year period 1976 2005 methods data obtained burgundy digestive cancer registry age standardised incidence rates trends incidence determined treatment stage diagnosis also investigated five year survival rates calculated results six hundred fifteen cases btc recorded significant change btc incidence 30 year period extrahepatic btc age standardised incidence rates 1 1 100 000 1976 80 2001 2005 rates respectively 0 3 0 2 100 000 intrahepatic btc proportion patients undergoing resection cure increased time 4 8 14 2 p 0 001 proportion stage ii cases ranged 3 2 7 1 vary significantly time p 0 55 cases metastatic unresectable diagnosis five year relative survival rates 4 5 1976 85 6 7 1996 2005 ranging 35 1 stages ii 4 3 advanced btc age stage diagnosis independent prognostic factors conclusions incidence btc remained stable burgundy past 30 years btc prognosis remains poor improved slightly time stn","probabilities":0.9799733,"Title":"Trends In The Incidence And Management Of Biliary Tract Cancer: A French Population-Based Study","Abstract":"Background & aims: The trends in incidence and management of biliary tract cancer (BTC) were investigated in a well-defined French population over a 30-year period (1976-2005). \r\n\r\n Methods: Data were obtained from the Burgundy digestive cancer registry. Age-standardised incidence rates and trends in incidence were determined. Treatment and stage at diagnosis were also investigated. Five-year survival rates were calculated. \r\n\r\n Results: Six hundred and fifteen cases of BTC were recorded. There was no significant change in BTC incidence over the 30-year period. For extrahepatic BTC age-standardised incidence rates were 1.1/100,000 for 1976-80 and 2001-2005. These rates were respectively 0.3 and 0.2/100,000 for intrahepatic BTC. The proportion of patients undergoing resection for cure increased over time from 4.8% to 14.2% (p<0.001). The proportion of stage I-II cases ranged from 3.2% to 7.1% but did not vary significantly over time (p=0.55). Most cases were metastatic or unresectable at diagnosis. Five-year relative survival rates were 4.5% for 1976-85 and 6.7% for 1996-2005, ranging from 35.1% for stages I-II to 4.3% for advanced BTC. Age and stage at diagnosis were independent prognostic factors. \r\n\r\n Conclusions: The incidence of BTC has remained stable in Burgundy over the past 30 years. BTC prognosis remains poor and has only improved slightly over time.","Source":"STN","category":"HUMAN","training_data":"Trends In The Incidence And Management Of Biliary Tract Cancer: A French Population-Based Study Background & aims: The trends in incidence and management of biliary tract cancer (BTC) were investigated in a well-defined French population over a 30-year period (1976-2005). \r\n\r\n Methods: Data were obtained from the Burgundy digestive cancer registry. Age-standardised incidence rates and trends in incidence were determined. Treatment and stage at diagnosis were also investigated. Five-year survival rates were calculated. \r\n\r\n Results: Six hundred and fifteen cases of BTC were recorded. There was no significant change in BTC incidence over the 30-year period. For extrahepatic BTC age-standardised incidence rates were 1.1/100,000 for 1976-80 and 2001-2005. These rates were respectively 0.3 and 0.2/100,000 for intrahepatic BTC. The proportion of patients undergoing resection for cure increased over time from 4.8% to 14.2% (p<0.001). The proportion of stage I-II cases ranged from 3.2% to 7.1% but did not vary significantly over time (p=0.55). Most cases were metastatic or unresectable at diagnosis. Five-year relative survival rates were 4.5% for 1976-85 and 6.7% for 1996-2005, ranging from 35.1% for stages I-II to 4.3% for advanced BTC. Age and stage at diagnosis were independent prognostic factors. \r\n\r\n Conclusions: The incidence of BTC has remained stable in Burgundy over the past 30 years. BTC prognosis remains poor and has only improved slightly over time. STN","prediction_labels":"HUMAN"},{"cleaned":"increased expression rbms3 predicts favorable prognosis human gallbladder carcinoma multiple regions short arm chromosome 3 frequently deleted variety solid tumors including gallbladder carcinoma gbc rna binding motif single stranded interacting protein 3 rbms3 tumor suppressor gene tsg located region however role rbms3 gbc remains unclear reverse transcription quantitative polymerase chain reaction rt qpcr western blotting performed evaluate mrna protein expression levels rbms3 41 fresh frozen gbc tissues paired normal tissues immunohistochemical assay performed tissue microarray tma consisting 125 cases gbc 47 normal controls microvessel density mvd counts determined using cd34 immunohistochemical staining moreover univariate multivariate analyses performed determine correlations rbms3 expression mvd patient prognosis cellular functions including proliferation clonogenicity apoptosis assessed identify vitro roles rbms3 revealed mrna protein expression levels rbms3 significantly lower gbc tissues normal controls multivariate cox regression analyses demonstrated cytoplasmic rbms3 expression independent prognostic factor correlated gbc angiogenesis histopathological differentiation tnm stage kaplan meier curves revealed patients lower cytoplasmic rbms3 levels significantly worse os patients higher cytoplasmic rbms3 expression additionally ectopic expression rbms3 markedly suppressed gbc cell proliferation clonogenicity promoted apoptosis vitro findings indicated potential cytoplasmic rbms3 tumor prognostic biomarker promising therapeutic target gbc google scholar","probabilities":0.9467213,"Title":"Increased Expression Of Rbms3 Predicts A Favorable Prognosis In Human Gallbladder Carcinoma","Abstract":"Multiple regions in the short arm of chromosome 3 are frequently deleted in a variety of solid tumors including gallbladder carcinoma (GBC). RNA binding motif, single‑stranded interacting protein 3 (RBMS3), a tumor suppressor gene (TSG), is located in this region. However, the role of RBMS3 in GBC remains unclear. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were performed to evaluate the mRNA and protein expression levels of RBMS3 in 41 fresh frozen GBC tissues and paired normal tissues. An immunohistochemical assay was performed on a tissue microarray (TMA, consisting of 125 cases GBC and 47 normal controls). Microvessel density (MVD) counts were determined using CD34 immunohistochemical staining. Moreover, univariate and multivariate analyses were performed to determine the correlations between RBMS3 expression, MVD and patient prognosis. Cellular functions including proliferation, clonogenicity and apoptosis, were assessed to further identify in vitro roles of RBMS3. It was revealed that both mRNA and protein expression levels of RBMS3 were significantly lower in GBC tissues than in normal controls. Multivariate Cox regression analyses demonstrated cytoplasmic RBMS3 expression as an independent prognostic factor correlated with GBC angiogenesis, histopathological differentiation and TNM stage. Kaplan‑Meier curves revealed that patients with lower cytoplasmic RBMS3 levels had a significantly worse OS than patients with higher cytoplasmic RBMS3 expression. Additionally, ectopic expression of RBMS3 markedly suppressed GBC cell proliferation and clonogenicity and promoted apoptosis in vitro. These findings indicated the potential of cytoplasmic RBMS3 as a tumor prognostic biomarker and a promising therapeutic target for GBC.","Source":"Google Scholar","category":"HUMAN","training_data":"Increased Expression Of Rbms3 Predicts A Favorable Prognosis In Human Gallbladder Carcinoma Multiple regions in the short arm of chromosome 3 are frequently deleted in a variety of solid tumors including gallbladder carcinoma (GBC). RNA binding motif, single‑stranded interacting protein 3 (RBMS3), a tumor suppressor gene (TSG), is located in this region. However, the role of RBMS3 in GBC remains unclear. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) and western blotting were performed to evaluate the mRNA and protein expression levels of RBMS3 in 41 fresh frozen GBC tissues and paired normal tissues. An immunohistochemical assay was performed on a tissue microarray (TMA, consisting of 125 cases GBC and 47 normal controls). Microvessel density (MVD) counts were determined using CD34 immunohistochemical staining. Moreover, univariate and multivariate analyses were performed to determine the correlations between RBMS3 expression, MVD and patient prognosis. Cellular functions including proliferation, clonogenicity and apoptosis, were assessed to further identify in vitro roles of RBMS3. It was revealed that both mRNA and protein expression levels of RBMS3 were significantly lower in GBC tissues than in normal controls. Multivariate Cox regression analyses demonstrated cytoplasmic RBMS3 expression as an independent prognostic factor correlated with GBC angiogenesis, histopathological differentiation and TNM stage. Kaplan‑Meier curves revealed that patients with lower cytoplasmic RBMS3 levels had a significantly worse OS than patients with higher cytoplasmic RBMS3 expression. Additionally, ectopic expression of RBMS3 markedly suppressed GBC cell proliferation and clonogenicity and promoted apoptosis in vitro. These findings indicated the potential of cytoplasmic RBMS3 as a tumor prognostic biomarker and a promising therapeutic target for GBC. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"prognostic scoring system based clinical features intrahepatic cholangiocarcinoma fudan score background objectives study propose clinical prognostic scoring system applicable intrahepatic cholangiocarcinoma icc evaluate prognostic validity american joint committee cancer ajcc 7th edition staging system patients methods retrospective univariate multivariate survival analyses conducted 344 patients icc underwent hepatectomy simple clinical prognostic scoring system fudan score developed based independent predictors prognostic validity assessed 74 patients unresected tumors compared ajcc 6th 7th edition systems results training set serum alkaline phosphatase level carbohydrate antigen 19 9 level tumor boundary type tumor size number intrahepatic tumors independent predictive factors survival icc incorporated fudan score three hundred forty four patients categorized four subsets 5 year overall survival rates 48 6 25 6 10 3 0 0 low intermediate high extremely high risk groups respectively discriminative ability fudan score better ajcc staging system well applied unresected patient set conclusions fudan score based clinical factors may provide relatively accurate prognostic prediction icc patients regardless resection status pubmed","probabilities":0.9799733,"Title":"A prognostic scoring system based on clinical features of intrahepatic cholangiocarcinoma: the Fudan score","Abstract":"BACKGROUND: The objectives of this study were to propose a clinical prognostic scoring system applicable for intrahepatic cholangiocarcinoma (ICC) and to evaluate the prognostic validity of the American Joint Committee on Cancer (AJCC) 7th edition staging system. PATIENTS AND METHODS: Retrospective univariate and multivariate survival analyses were conducted for 344 patients with ICC who underwent hepatectomy. A simple clinical prognostic scoring system (Fudan score) was developed based on the independent predictors. The prognostic validity was assessed in 74 patients with unresected tumors and compared with the AJCC 6th and 7th edition systems. RESULTS: In the training set, serum alkaline phosphatase level, carbohydrate antigen 19-9 level, tumor boundary type, tumor size, and number of intrahepatic tumors were independent predictive factors of survival in ICC and were incorporated into the Fudan score. Three hundred forty-four patients were categorized into four subsets with 5-year overall survival rates of 48.6%, 25.6%, 10.3%, and 0.0% for low-, intermediate-, high-, and extremely high-risk groups, respectively. The discriminative ability of the Fudan score was better than that of the AJCC staging system and well applied in the unresected patient set. CONCLUSIONS: A Fudan score based on clinical factors may provide a relatively accurate prognostic prediction for ICC patients regardless of resection status.","Source":"PubMed","category":"HUMAN","training_data":"A prognostic scoring system based on clinical features of intrahepatic cholangiocarcinoma: the Fudan score BACKGROUND: The objectives of this study were to propose a clinical prognostic scoring system applicable for intrahepatic cholangiocarcinoma (ICC) and to evaluate the prognostic validity of the American Joint Committee on Cancer (AJCC) 7th edition staging system. PATIENTS AND METHODS: Retrospective univariate and multivariate survival analyses were conducted for 344 patients with ICC who underwent hepatectomy. A simple clinical prognostic scoring system (Fudan score) was developed based on the independent predictors. The prognostic validity was assessed in 74 patients with unresected tumors and compared with the AJCC 6th and 7th edition systems. RESULTS: In the training set, serum alkaline phosphatase level, carbohydrate antigen 19-9 level, tumor boundary type, tumor size, and number of intrahepatic tumors were independent predictive factors of survival in ICC and were incorporated into the Fudan score. Three hundred forty-four patients were categorized into four subsets with 5-year overall survival rates of 48.6%, 25.6%, 10.3%, and 0.0% for low-, intermediate-, high-, and extremely high-risk groups, respectively. The discriminative ability of the Fudan score was better than that of the AJCC staging system and well applied in the unresected patient set. CONCLUSIONS: A Fudan score based on clinical factors may provide a relatively accurate prognostic prediction for ICC patients regardless of resection status. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic risk factors associated recurrence metastasis radical resection patients hepatolithiasis complicated intrahepatic cholangiocarcinoma objective study analyze predictive significance different prognostic factors associated recurrence metastasis radical resection patients hepatolithiasis complicated intrahepatic cholangiocarcinoma hla ihcc total 138 patients hla ihcc admitted april 2006 april 2009 selected study divided two groups without recurrence metastasis radical resection surgery patients followed 5 years monitor recurrence metastasis general clinical data two groups analyzed evaluate relevant risk factors study showed recurrence metastasis occurred 48 patients rate 34 8 recurrence liver accounted 85 4 41 cases whereas lung bone metastases occurred rates 8 3 4 cases 6 3 3 cases respectively univariate analysis revealed ca19 9 tumor diameter tumor amount lymphatic metastasis ajcc stage recurrence metastasis group significantly different non recurrence metastasis patients p 0 05 multivariate analysis showed ca19 9 200 u ml tumor diameter 5 cm presence multiple tumors lymphatic metastasis iii iv ajcc stages independent risk factors tumor recurrence metastasis radical surgery p 0 05 5 years follow 65 patients 47 1 died including 31 recurrence metastasis 34 non recurrence metastasis groups accounting 64 5 31 48 37 8 34 90 mortality two groups respectively thus 5 year mortality recurrence metastasis group significantly higher non recurrence metastasis group p 0 05 ca19 9 antigen tumor diameter tumor amount lymphatic metastasis ajcc stage significantly associated increased risk post resection recurrence metastasis hla ihcc massive lymphadenectomy surgery perioperative control inflammation decreased risk recurrence metastasis improved disease prognosis pubmed","probabilities":0.9799733,"Title":"Prognostic Risk Factors Associated with Recurrence and Metastasis After Radical Resection in Patients with Hepatolithiasis Complicated by Intrahepatic Cholangiocarcinoma","Abstract":"The objective of this study was to analyze the predictive significance of different prognostic factors associated with recurrence and metastasis after the radical resection in patients with hepatolithiasis complicated by intrahepatic cholangiocarcinoma (HLA/IHCC). A total of 138 patients with HLA/IHCC admitted during April 2006-April 2009 were selected for this study and they were divided into two groups, with and without recurrence/metastasis. After a radical resection surgery, the patients were followed up for 5 years to monitor the recurrence and/or metastasis. The general and clinical data of the two groups were analyzed to evaluate the relevant risk factors. The study showed that recurrence/metastasis occurred in 48 patients with a rate of 34.8 %. Recurrence in liver accounted for 85.4 % (41 cases), whereas in lung and bone metastases occurred at rates of 8.3 % (4 cases) and 6.3 % (3 cases), respectively. Univariate analysis revealed that CA19-9, tumor diameter, tumor amount, lymphatic metastasis, and AJCC stage of the recurrence/metastasis group were significantly different from those of the non-recurrence/metastasis patients (p < 0.05). The multivariate analysis showed that CA19-9 > 200 U/mL, tumor diameter >5 cm, presence of multiple tumors, lymphatic metastasis, and III-IV AJCC stages were independent risk factors of tumor recurrence and metastasis after the radical surgery (p < 0.05). During the 5 years of follow-up, 65 patients (47.1 %) died, including 31 in the recurrence/metastasis and 34 in the non-recurrence/metastasis groups, accounting for 64.5 % (31/48) and 37.8 % (34/90) of mortality in the two groups, respectively. Thus, the 5-year mortality in the recurrence/metastasis group was significantly higher than that in the non-recurrence/metastasis group (p < 0.05). The CA19-9 antigen, tumor diameter, tumor amount, lymphatic metastasis, and AJCC stage were significantly associated with increased risk of post-resection recurrence and metastasis of HLA/IHCC. The massive lymphadenectomy during the surgery and perioperative control of inflammation decreased the risk of recurrence/metastasis and further improved the disease prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Risk Factors Associated with Recurrence and Metastasis After Radical Resection in Patients with Hepatolithiasis Complicated by Intrahepatic Cholangiocarcinoma The objective of this study was to analyze the predictive significance of different prognostic factors associated with recurrence and metastasis after the radical resection in patients with hepatolithiasis complicated by intrahepatic cholangiocarcinoma (HLA/IHCC). A total of 138 patients with HLA/IHCC admitted during April 2006-April 2009 were selected for this study and they were divided into two groups, with and without recurrence/metastasis. After a radical resection surgery, the patients were followed up for 5 years to monitor the recurrence and/or metastasis. The general and clinical data of the two groups were analyzed to evaluate the relevant risk factors. The study showed that recurrence/metastasis occurred in 48 patients with a rate of 34.8 %. Recurrence in liver accounted for 85.4 % (41 cases), whereas in lung and bone metastases occurred at rates of 8.3 % (4 cases) and 6.3 % (3 cases), respectively. Univariate analysis revealed that CA19-9, tumor diameter, tumor amount, lymphatic metastasis, and AJCC stage of the recurrence/metastasis group were significantly different from those of the non-recurrence/metastasis patients (p < 0.05). The multivariate analysis showed that CA19-9 > 200 U/mL, tumor diameter >5 cm, presence of multiple tumors, lymphatic metastasis, and III-IV AJCC stages were independent risk factors of tumor recurrence and metastasis after the radical surgery (p < 0.05). During the 5 years of follow-up, 65 patients (47.1 %) died, including 31 in the recurrence/metastasis and 34 in the non-recurrence/metastasis groups, accounting for 64.5 % (31/48) and 37.8 % (34/90) of mortality in the two groups, respectively. Thus, the 5-year mortality in the recurrence/metastasis group was significantly higher than that in the non-recurrence/metastasis group (p < 0.05). The CA19-9 antigen, tumor diameter, tumor amount, lymphatic metastasis, and AJCC stage were significantly associated with increased risk of post-resection recurrence and metastasis of HLA/IHCC. The massive lymphadenectomy during the surgery and perioperative control of inflammation decreased the risk of recurrence/metastasis and further improved the disease prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"twenty six cases advanced ampullary adenocarcinoma treated systemic chemotherapy objective ampullary adenocarcinoma rare disease entity little information regarding tumors available aim present study clarify treatment outcome systemic chemotherapy patients advanced ampullary adenocarcinoma methods study consisted retrospective review data obtained patients diagnosed advanced ampullary adenocarcinoma received non surgical treatment single institution 1997 2010 results identified 26 patients 15 men 11 women median age 62 0 years received treatment advanced ampullary adenocarcinoma twelve patients stage iv disease 14 recurrences chemotherapy regimens consisted 5 fluorouracil based regimens 5 fluorouracil cisplatin n 3 tegafur uracil doxorubicin n 5 tegafur gimeracil oteracil potassium n 3 gemcitabine based regimens gemcitabine n 10 gemcitabine cisplatin n 5 overall response rate 7 7 median progression free survival period 3 2 months 2 5 months 5 fluorouracil group vs 3 5 months gemcitabine group median overall survival time 9 1 months 8 0 months 5 fluorouracil group vs 12 3 months gemcitabine group median overall survival significantly longer stage iv disease recurrent disease histological phenotype determined 10 26 patients eight patients intestinal type adenocarcinomas remaining two patients pancreatobiliary type adenocarcinomas conclusions treatment outcome patients advanced ampullary adenocarcinoma poor development novel treatments necessary improve prognosis pubmed","probabilities":0.9799733,"Title":"Twenty-six cases of advanced ampullary adenocarcinoma treated with systemic chemotherapy","Abstract":"OBJECTIVE: Ampullary adenocarcinoma is a rare disease entity and little information regarding these tumors is available. The aim of the present study was to clarify the treatment outcome of systemic chemotherapy in patients with advanced ampullary adenocarcinoma. METHODS: This study consisted of a retrospective review of data obtained from patients diagnosed as having advanced ampullary adenocarcinoma who received non-surgical treatment at a single institution between 1997 and 2010. RESULTS: We identified 26 patients (15 men, 11 women; median age, 62.0 years) who received treatment for advanced ampullary adenocarcinoma. Twelve patients had Stage IV disease and 14 had recurrences. The chemotherapy regimens consisted of 5-fluorouracil-based regimens (5-fluorouracil + cisplatin, n = 3; tegafur-uracil + doxorubicin, n = 5 and tegafur, gimeracil and oteracil potassium, n = 3) and gemcitabine-based regimens (gemcitabine, n = 10 and gemcitabine + cisplatin, n = 5). The overall response rate was 7.7%. The median progression-free survival period was 3.2 months (2.5 months in the 5-fluorouracil group vs. 3.5 months in the gemcitabine group), and the median overall survival time was 9.1 months (8.0 months in the 5-fluorouracil group vs. 12.3 months in the gemcitabine group). The median overall survival was significantly longer in stage IV disease than in recurrent disease. The histological phenotype was determined in 10 of the 26 patients. Eight patients had intestinal-type adenocarcinomas and remaining two patients had pancreatobiliary-type adenocarcinomas. CONCLUSIONS: The treatment outcome of patients with advanced ampullary adenocarcinoma was poor. Further development of novel treatments is necessary to improve the prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Twenty-six cases of advanced ampullary adenocarcinoma treated with systemic chemotherapy OBJECTIVE: Ampullary adenocarcinoma is a rare disease entity and little information regarding these tumors is available. The aim of the present study was to clarify the treatment outcome of systemic chemotherapy in patients with advanced ampullary adenocarcinoma. METHODS: This study consisted of a retrospective review of data obtained from patients diagnosed as having advanced ampullary adenocarcinoma who received non-surgical treatment at a single institution between 1997 and 2010. RESULTS: We identified 26 patients (15 men, 11 women; median age, 62.0 years) who received treatment for advanced ampullary adenocarcinoma. Twelve patients had Stage IV disease and 14 had recurrences. The chemotherapy regimens consisted of 5-fluorouracil-based regimens (5-fluorouracil + cisplatin, n = 3; tegafur-uracil + doxorubicin, n = 5 and tegafur, gimeracil and oteracil potassium, n = 3) and gemcitabine-based regimens (gemcitabine, n = 10 and gemcitabine + cisplatin, n = 5). The overall response rate was 7.7%. The median progression-free survival period was 3.2 months (2.5 months in the 5-fluorouracil group vs. 3.5 months in the gemcitabine group), and the median overall survival time was 9.1 months (8.0 months in the 5-fluorouracil group vs. 12.3 months in the gemcitabine group). The median overall survival was significantly longer in stage IV disease than in recurrent disease. The histological phenotype was determined in 10 of the 26 patients. Eight patients had intestinal-type adenocarcinomas and remaining two patients had pancreatobiliary-type adenocarcinomas. CONCLUSIONS: The treatment outcome of patients with advanced ampullary adenocarcinoma was poor. Further development of novel treatments is necessary to improve the prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"modified glasgow prognostic score patients gemcitabine refractory biliary tract cancer background standard second line chemotherapy yet established gemcitabine refractory biliary tract cancer btc patients methods conducted multivariable cox regression analysis examine prognostic factors overall survival os patients received gemcitabine based treatment results forty six patients received second line chemotherapy median serum carbohydrate antigen 19 9 ca 19 9 value 487 u ml modified glasgow prognostic score mgps 0 n 24 1 n 10 2 n 10 second line chemotherapy included 1 20 patients gemcitabine based 20 tyrosine kinase inhibitors five median os 8 3 months median progression free survival 3 0 months multivariate analysis identified serum ca 19 9 500 u ml mgps 1 presence liver metastasis significant prognostic factors os conclusion second line chemotherapy gemcitabine refractory btc remains inadequate randomized trials appropriate stratification criteria required pubmed","probabilities":0.9799733,"Title":"The Modified Glasgow Prognostic Score in Patients with Gemcitabine-refractory Biliary Tract Cancer","Abstract":"BACKGROUND: No standard second-line chemotherapy has been yet established for gemcitabine-refractory biliary tract cancer (BTC). PATIENTS AND METHODS: We conducted multivariable Cox regression analysis to examine the prognostic factors for overall survival (OS) in patients who had received gemcitabine-based treatment. RESULTS: Forty-six patients received second-line chemotherapy. The median serum carbohydrate antigen 19-9 (CA 19-9) value was 487 U/ml. The modified Glasgow prognostic score (mGPS) was: 0 (n=24), 1 (n=10), or 2 (n=10). The second-line chemotherapy included: S-1 in 20 patients, gemcitabine-based in 20, and tyrosine kinase inhibitors in five. The median OS was 8.3 months, and the median progression-free survival was 3.0 months. Multivariate analysis identified serum CA 19-9 ≥500 U/ml, mGPS ≥1, and presence of liver metastasis as significant prognostic factors for OS. CONCLUSION: Second-line chemotherapy for gemcitabine-refractory BTC remains inadequate. Randomized trials with appropriate stratification criteria are required.","Source":"PubMed","category":"HUMAN","training_data":"The Modified Glasgow Prognostic Score in Patients with Gemcitabine-refractory Biliary Tract Cancer BACKGROUND: No standard second-line chemotherapy has been yet established for gemcitabine-refractory biliary tract cancer (BTC). PATIENTS AND METHODS: We conducted multivariable Cox regression analysis to examine the prognostic factors for overall survival (OS) in patients who had received gemcitabine-based treatment. RESULTS: Forty-six patients received second-line chemotherapy. The median serum carbohydrate antigen 19-9 (CA 19-9) value was 487 U/ml. The modified Glasgow prognostic score (mGPS) was: 0 (n=24), 1 (n=10), or 2 (n=10). The second-line chemotherapy included: S-1 in 20 patients, gemcitabine-based in 20, and tyrosine kinase inhibitors in five. The median OS was 8.3 months, and the median progression-free survival was 3.0 months. Multivariate analysis identified serum CA 19-9 ≥500 U/ml, mGPS ≥1, and presence of liver metastasis as significant prognostic factors for OS. CONCLUSION: Second-line chemotherapy for gemcitabine-refractory BTC remains inadequate. Randomized trials with appropriate stratification criteria are required. PubMed","prediction_labels":"HUMAN"},{"cleaned":"adjuvant gemcitabine monotherapy resectable perihilar cholangiocarcinoma lymph node involvement propensity score matching analysis purpose aim study evaluate efficacy adjuvant gemcitabine monotherapy following resection perihilar cholangiocarcinoma lymph node involvement methods performed retrospective analysis 180 patients undergoing resection perihilar cholangiocarcinoma lymph node involvement 2001 2012 patients divided two groups according presence n 67 absence n 113 adjuvant gemcitabine monotherapy univariate multivariate analyses performed followed propensity score matching analysis adjust differences baseline characteristics groups results overall survival rates surgery median survival times patients treated adjuvant chemotherapy significantly longer treated without adjuvant chemotherapy 32 9 vs 15 0 5 years 37 vs 20 months p 0 001 multivariate analysis indicated adjuvant chemotherapy residual microscopic tumor pathological stage independent prognostic factors survival two new cohorts 32 patients generated following 1 1 propensity score matching overall survival rate adjuvant chemotherapy group found significantly longer surgery alone group 43 2 vs 15 6 5 years p 0 001 conclusion adjuvant gemcitabine monotherapy may improve survival node positive perihilar cholangiocarcinoma patients pubmed","probabilities":0.9799733,"Title":"Adjuvant gemcitabine monotherapy for resectable perihilar cholangiocarcinoma with lymph node involvement: a propensity score matching analysis","Abstract":"PURPOSE: The aim of this study was to evaluate the efficacy of adjuvant gemcitabine monotherapy following resection for perihilar cholangiocarcinoma with lymph node involvement. METHODS: We performed a retrospective analysis of 180 patients undergoing resection for perihilar cholangiocarcinoma with lymph node involvement between 2001 and 2012. The patients were divided into two groups according to the presence (n = 67) or absence (n = 113) of adjuvant gemcitabine monotherapy. Univariate and multivariate analyses were performed followed by a propensity score matching analysis to adjust for the differences in the baseline characteristics of the groups. RESULTS: The overall survival rates after surgery and the median survival times in patients who were treated with adjuvant chemotherapy were significantly longer than those who were treated without adjuvant chemotherapy (32.9 vs. 15.0 % at 5 years, 37 vs. 20 months, P = 0.001). A multivariate analysis indicated that adjuvant chemotherapy, a residual microscopic tumor, and pathological T stage were independent prognostic factors for survival. After two new cohorts of 32 patients were generated following 1:1 propensity score matching, the overall survival rate in the adjuvant chemotherapy group was found to be significantly longer than that in the surgery alone group (43.2 vs. 15.6 % at 5 years, P = 0.001). CONCLUSION: Adjuvant gemcitabine monotherapy may improve survival in node-positive perihilar cholangiocarcinoma patients.","Source":"PubMed","category":"HUMAN","training_data":"Adjuvant gemcitabine monotherapy for resectable perihilar cholangiocarcinoma with lymph node involvement: a propensity score matching analysis PURPOSE: The aim of this study was to evaluate the efficacy of adjuvant gemcitabine monotherapy following resection for perihilar cholangiocarcinoma with lymph node involvement. METHODS: We performed a retrospective analysis of 180 patients undergoing resection for perihilar cholangiocarcinoma with lymph node involvement between 2001 and 2012. The patients were divided into two groups according to the presence (n = 67) or absence (n = 113) of adjuvant gemcitabine monotherapy. Univariate and multivariate analyses were performed followed by a propensity score matching analysis to adjust for the differences in the baseline characteristics of the groups. RESULTS: The overall survival rates after surgery and the median survival times in patients who were treated with adjuvant chemotherapy were significantly longer than those who were treated without adjuvant chemotherapy (32.9 vs. 15.0 % at 5 years, 37 vs. 20 months, P = 0.001). A multivariate analysis indicated that adjuvant chemotherapy, a residual microscopic tumor, and pathological T stage were independent prognostic factors for survival. After two new cohorts of 32 patients were generated following 1:1 propensity score matching, the overall survival rate in the adjuvant chemotherapy group was found to be significantly longer than that in the surgery alone group (43.2 vs. 15.6 % at 5 years, P = 0.001). CONCLUSION: Adjuvant gemcitabine monotherapy may improve survival in node-positive perihilar cholangiocarcinoma patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival cohort patients intermediate advanced gall bladder cancer treated prospective therapeutic protocol purpose evaluate results prospective therapeutic protocol long term follow terms survival rates cohort patients treated intermediate advanced gbc gbc methods prospective cohort patients intermediate advanced stages gbc treated 1996 2006 cases treated partial hepatic segmentectomy segments ivb v regional lymph node dissection six cycles patient chemotherapy 5 fu leukovorin average follow 31 5 months morbidity operative mortality hepatic lymphatic infiltration actuarial survival measured descriptive statistics applied well bivariate analysis applying fisher exact test non parametrical tests kaplan meier survival curves also logistic regression proportional risk cox applied results 40 patients included protocol average age 59 5 years 40 85 years 28 women 70 depth wall infiltration muscular 8 patients 20 subserosal 12 patients 30 serosal 12 patients 30 perivesicular adipose tissue 8 patients 20 series morbidity 27 5 operative mortality chemotherapy well tolerated overall actuarial survival series 50 60 months conclusion protocol treatment morbidity mortality survival rates similar previously reported series pubmed","probabilities":0.7966102,"Title":"Survival of a cohort of patients with intermediate and advanced gall bladder cancer treated with a prospective therapeutic protocol","Abstract":"PURPOSE: To evaluate the results of a prospective therapeutic protocol with long-term follow up in terms of survival rates in a cohort of patients treated with Intermediate and Advanced GBC (GBC). METHODS: Prospective cohort of patients with intermediate and advanced stages of GBC treated between 1996 and 2006. All cases were treated with a partial hepatic segmentectomy on segments IVb and V and a regional lymph node dissection and six cycles of out-patient chemotherapy (5-FU and leukovorin). With an average follow-up of 31.5 months, the morbidity, operative mortality, hepatic and lymphatic infiltration and actuarial survival were measured. Descriptive statistics were applied as well as bivariate analysis applying Fisher's exact test and non-parametrical tests and Kaplan Meier survival curves. Also logistic regression and proportional risk of Cox were applied. RESULTS: 40 patients were included in this protocol, with an average age of 59.5 years (40-85 years), of which 28 were women (70%). Depth of wall infiltration: muscular 8 patients (20%), subserosal 12 patients (30%), serosal 12 patients (30%) and perivesicular adipose tissue 8 patients (20%). The series morbidity was 27.5%. There was no operative mortality. The chemotherapy was well tolerated. The overall actuarial survival in the series was 50% at 60 months. CONCLUSION: Our protocol treatment has morbidity, mortality and survival rates similar to previously reported series.","Source":"PubMed","category":"HUMAN","training_data":"Survival of a cohort of patients with intermediate and advanced gall bladder cancer treated with a prospective therapeutic protocol PURPOSE: To evaluate the results of a prospective therapeutic protocol with long-term follow up in terms of survival rates in a cohort of patients treated with Intermediate and Advanced GBC (GBC). METHODS: Prospective cohort of patients with intermediate and advanced stages of GBC treated between 1996 and 2006. All cases were treated with a partial hepatic segmentectomy on segments IVb and V and a regional lymph node dissection and six cycles of out-patient chemotherapy (5-FU and leukovorin). With an average follow-up of 31.5 months, the morbidity, operative mortality, hepatic and lymphatic infiltration and actuarial survival were measured. Descriptive statistics were applied as well as bivariate analysis applying Fisher's exact test and non-parametrical tests and Kaplan Meier survival curves. Also logistic regression and proportional risk of Cox were applied. RESULTS: 40 patients were included in this protocol, with an average age of 59.5 years (40-85 years), of which 28 were women (70%). Depth of wall infiltration: muscular 8 patients (20%), subserosal 12 patients (30%), serosal 12 patients (30%) and perivesicular adipose tissue 8 patients (20%). The series morbidity was 27.5%. There was no operative mortality. The chemotherapy was well tolerated. The overall actuarial survival in the series was 50% at 60 months. CONCLUSION: Our protocol treatment has morbidity, mortality and survival rates similar to previously reported series. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tyrosine phosphatase activity required response src kinase inhibition cholangiocarcinoma background cancer biliary tract cholangiocarcinoma cca increasing incidence limited treatment options attempt understand signaling pathways driving oncogenesis impacting response therapy others identified altered activation transcriptional co activator yes associated protein yap cca canonical regulatory pathways impacting yap consist serine kinases however recently demonstrated central role tyrosine phosphorylation regulating yap function cca herein explore role tyrosine phosphatases regulating yap tyrosine phosphorylation methods silico analysis tcga cholangiocarcinoma dataset undertaken specifically evaluating tyrosine phosphatase levels molecular studies utilized human cca cell lines hucct 1 kmch well murine cca cell line sb1 expressing flag tagged yap baseline tyrosine phosphatase levels assessed rt pcr immunoblot yap interacting phosphatases identified co immunoprecipitation tyrosine phosphorylation inhibited utilizing multi kinase inhibitor dasatinib pan tyrosine phosphatase inhibitor sodium orthovanadate na3vo4 selective shp1 2 inhibitor nsc87877 utilized tyrosine phosphorylation assessed immunoblot yap transcriptional activity evaluated rt pcr apoptosis evaluated caspase 3 7 assay results multiple tyrosine phosphatases noted expressed lower levels tumor versus normal adjacent liver tcga rnaseq dataset yap interacting tyrosine phosphatases identified co ip included ptpn1 11 23 ptprk profiling tyrosine phosphatase levels rt pcr immunoblot demonstrated higher levels kmch cells compared hucct 1 notably yap interacting phosphatase ptpn11 shp2 elevated consistent anticipated function phosphatases immunoblot demonstrated lower levels tyrosine phosphorylated yap p yapy357 kmch cells compared hucct 1 role shp2 probed incubation kmch hucct 1 cells nsc87877 associated increase p yapy357 levels yap co transcriptional activity conversely incubation hucct 1 cells dasatinib rapidly decreased p yapy357 levels effect diminished pre incubation either na3vo4or nsc87877 effect yap tyrosine phosphorylation paralleled effects apoptosis incubation hucct 1 cells dasatinib lead apoptotic response measured caspase 3 7 assay eliminated pre incubation na3vo4 nsc87877 conclusions inhibition tyrosine phosphatase shp2 associated elevated p yapy357 levels elevated yap co transcriptional activity blunted therapeutic response dasatinib cholangiocarcinoma cell lines google scholar","probabilities":0.9467213,"Title":"Tyrosine Phosphatase Activity Is Required For Response To Src Kinase Inhibition In Cholangiocarcinoma","Abstract":"Background: Cancer of the biliary tract, cholangiocarcinoma (CCA), is increasing in incidence and has limited treatment options. In an attempt to further understand signaling pathways driving oncogenesis and impacting response to therapy we, and others, have identified altered activation of the transcriptional co-activator, Yes- associated protein (YAP) in CCA. Canonical regulatory pathways impacting YAP consist of serine kinases; however, more recently we have demonstrated a central role for tyrosine phosphorylation in regulating YAP function in CCA. Herein we explore the role of tyrosine phosphatases in regulating YAP tyrosine phosphorylation. \nMethods: In silico analysis of the TCGA cholangiocarcinoma dataset was undertaken specifically evaluating tyrosine phosphatase levels. Molecular studies utilized the human CCA cell lines HuCCT-1 and KMCH as well as the murine CCA cell line SB1 (expressing a flag-tagged YAP). Baseline tyrosine phosphatase levels were assessed by RT-PCR and immunoblot. YAP-interacting phosphatases were identified by co-immunoprecipitation. Tyrosine phosphorylation was inhibited utilizing the multi-kinase inhibitor dasatinib. The pan-tyrosine phosphatase inhibitor sodium orthovanadate (Na3VO4) and the selective SHP1/2 inhibitor NSC87877 were utilized. Tyrosine phosphorylation was assessed by immunoblot. YAP transcriptional activity was evaluated by RT-PCR. Apoptosis was evaluated by caspase 3/7 assay. \nResults: Multiple tyrosine phosphatases were noted to be expressed at lower levels in tumor versus normal adjacent liver in the TCGA RNAseq dataset. YAP-interacting tyrosine phosphatases identified by co-IP included PTPN1, 11, 23, and PTPRK. Profiling of tyrosine phosphatase levels by RT-PCR and immunoblot demonstrated higher levels in KMCH cells compared to HuCCT-1; notably the YAP-interacting phosphatase PTPN11 (SHP2) was elevated. Consistent with the anticipated function of the phosphatases, immunoblot demonstrated lower levels of tyrosine phosphorylated YAP (p-YAPY357) in KMCH cells compared to HuCCT-1. The role of SHP2 was further probed by incubation of KMCH and HuCCT-1 cells with NSC87877 which was associated with an increase in p-YAPY357 levels and YAP co-transcriptional activity. Conversely, incubation of HuCCT-1 cells with dasatinib rapidly decreased p-YAPY357 levels; and this effect was diminished by pre-incubation with either Na3VO4or NSC87877. The effect on YAP tyrosine phosphorylation paralleled effects on apoptosis; incubation of HuCCT-1 cells with dasatinib lead to an apoptotic response as measured by caspase 3/7 assay, which was eliminated by pre-incubation with Na3VO4 or NSC87877.\nConclusions: Inhibition of the tyrosine phosphatase SHP2 is associated with elevated p-YAPY357 levels, elevated YAP co-transcriptional activity, and a blunted therapeutic response to dasatinib in cholangiocarcinoma cell lines.","Source":"Google Scholar","category":"ANIMAL","training_data":"Tyrosine Phosphatase Activity Is Required For Response To Src Kinase Inhibition In Cholangiocarcinoma Background: Cancer of the biliary tract, cholangiocarcinoma (CCA), is increasing in incidence and has limited treatment options. In an attempt to further understand signaling pathways driving oncogenesis and impacting response to therapy we, and others, have identified altered activation of the transcriptional co-activator, Yes- associated protein (YAP) in CCA. Canonical regulatory pathways impacting YAP consist of serine kinases; however, more recently we have demonstrated a central role for tyrosine phosphorylation in regulating YAP function in CCA. Herein we explore the role of tyrosine phosphatases in regulating YAP tyrosine phosphorylation. \nMethods: In silico analysis of the TCGA cholangiocarcinoma dataset was undertaken specifically evaluating tyrosine phosphatase levels. Molecular studies utilized the human CCA cell lines HuCCT-1 and KMCH as well as the murine CCA cell line SB1 (expressing a flag-tagged YAP). Baseline tyrosine phosphatase levels were assessed by RT-PCR and immunoblot. YAP-interacting phosphatases were identified by co-immunoprecipitation. Tyrosine phosphorylation was inhibited utilizing the multi-kinase inhibitor dasatinib. The pan-tyrosine phosphatase inhibitor sodium orthovanadate (Na3VO4) and the selective SHP1/2 inhibitor NSC87877 were utilized. Tyrosine phosphorylation was assessed by immunoblot. YAP transcriptional activity was evaluated by RT-PCR. Apoptosis was evaluated by caspase 3/7 assay. \nResults: Multiple tyrosine phosphatases were noted to be expressed at lower levels in tumor versus normal adjacent liver in the TCGA RNAseq dataset. YAP-interacting tyrosine phosphatases identified by co-IP included PTPN1, 11, 23, and PTPRK. Profiling of tyrosine phosphatase levels by RT-PCR and immunoblot demonstrated higher levels in KMCH cells compared to HuCCT-1; notably the YAP-interacting phosphatase PTPN11 (SHP2) was elevated. Consistent with the anticipated function of the phosphatases, immunoblot demonstrated lower levels of tyrosine phosphorylated YAP (p-YAPY357) in KMCH cells compared to HuCCT-1. The role of SHP2 was further probed by incubation of KMCH and HuCCT-1 cells with NSC87877 which was associated with an increase in p-YAPY357 levels and YAP co-transcriptional activity. Conversely, incubation of HuCCT-1 cells with dasatinib rapidly decreased p-YAPY357 levels; and this effect was diminished by pre-incubation with either Na3VO4or NSC87877. The effect on YAP tyrosine phosphorylation paralleled effects on apoptosis; incubation of HuCCT-1 cells with dasatinib lead to an apoptotic response as measured by caspase 3/7 assay, which was eliminated by pre-incubation with Na3VO4 or NSC87877.\nConclusions: Inhibition of the tyrosine phosphatase SHP2 is associated with elevated p-YAPY357 levels, elevated YAP co-transcriptional activity, and a blunted therapeutic response to dasatinib in cholangiocarcinoma cell lines. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"vivo validation cancer genes using liver organoids abstract available google scholar","probabilities":0.9799733,"Title":"In-Vivo Validation Of Cancer Genes Using Liver Organoids","Abstract":"Abstract not available","Source":"Google Scholar","category":"ANIMAL","training_data":"In-Vivo Validation Of Cancer Genes Using Liver Organoids Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"american joint committee cancer staging resected perihilar cholangiocarcinoma comparison 6th 7th editions objectives study conducted evaluate prognostic value respectively 6th 7th editions american joint committee cancer ajcc staging system patients resected perihilar cholangiocarcinoma phc methods patients underwent resection phc 1991 2012 identified prospective databases two centres overall survival estimated using kaplan meier method compared across stage groups log rank test concordance index brier score used compare prognostic accuracy staging systems results data total 306 patients analysed staging according 7th edition upstaged 63 patients comparison staging 6th edition log rank p value staging systems highly statistically significant p 0 001 staging according 6th edition categorized 93 patients stage ii disease whereas staging according 7th edition distributed patients equally across stages prognostic accuracy similar staging systems concordance index 0 59 brier score 0 17 6th 7th editions prognostic accuracy achieved using alternative tumour node metastasis tnm stage grouping simplified four rather six stage groups conclusions 6th 7th editions ajcc staging system phc similar prognostic accuracy prognostic factors potentially improve individual patient prognostication pubmed","probabilities":0.9799733,"Title":"American Joint Committee on Cancer staging for resected perihilar cholangiocarcinoma: a comparison of the 6th and 7th editions","Abstract":"OBJECTIVES: This study was conducted to evaluate the prognostic value of, respectively, the 6th and 7th editions of the American Joint Committee on Cancer (AJCC) staging system for patients with resected perihilar cholangiocarcinoma (PHC). METHODS: Patients who underwent resection of PHC between 1991 and 2012 were identified from prospective databases at two centres. Overall survival was estimated using the Kaplan-Meier method and compared across stage groups with the log-rank test. The concordance index and Brier score were used to compare the prognostic accuracy of the staging systems. RESULTS: Data for a total of 306 patients were analysed. Staging according to the 7th edition upstaged 63% of patients in comparison with staging by the 6th edition. The log-rank P-value for both staging systems was highly statistically significant (P < 0.001). Staging according to the 6th edition categorized 93% of patients as having stage I or II disease, whereas staging according to the 7th edition distributed patients more equally across stages. Prognostic accuracy was similar between the staging systems: the concordance index was 0.59 and the Brier score 0.17 for both the 6th and 7th editions. The same prognostic accuracy was achieved using an alternative tumour-node-metastasis (TNM) stage grouping simplified to four rather than six stage groups. CONCLUSIONS: The 6th and 7th editions of the AJCC staging system for PHC have similar prognostic accuracy. Other prognostic factors can potentially improve individual patient prognostication.","Source":"PubMed","category":"HUMAN","training_data":"American Joint Committee on Cancer staging for resected perihilar cholangiocarcinoma: a comparison of the 6th and 7th editions OBJECTIVES: This study was conducted to evaluate the prognostic value of, respectively, the 6th and 7th editions of the American Joint Committee on Cancer (AJCC) staging system for patients with resected perihilar cholangiocarcinoma (PHC). METHODS: Patients who underwent resection of PHC between 1991 and 2012 were identified from prospective databases at two centres. Overall survival was estimated using the Kaplan-Meier method and compared across stage groups with the log-rank test. The concordance index and Brier score were used to compare the prognostic accuracy of the staging systems. RESULTS: Data for a total of 306 patients were analysed. Staging according to the 7th edition upstaged 63% of patients in comparison with staging by the 6th edition. The log-rank P-value for both staging systems was highly statistically significant (P < 0.001). Staging according to the 6th edition categorized 93% of patients as having stage I or II disease, whereas staging according to the 7th edition distributed patients more equally across stages. Prognostic accuracy was similar between the staging systems: the concordance index was 0.59 and the Brier score 0.17 for both the 6th and 7th editions. The same prognostic accuracy was achieved using an alternative tumour-node-metastasis (TNM) stage grouping simplified to four rather than six stage groups. CONCLUSIONS: The 6th and 7th editions of the AJCC staging system for PHC have similar prognostic accuracy. Other prognostic factors can potentially improve individual patient prognostication. PubMed","prediction_labels":"HUMAN"},{"cleaned":"combined extrahepatic bile duct resection locally advanced gallbladder carcinoma work background prophylactic combined extrahepatic bile duct resection remains controversial locally advanced gallbladder carcinoma without extrahepatic bile duct invasion aim study resolve issue establish appropriate surgery locally advanced gallbladder carcinoma methods total 52 patients underwent surgical resection combined extrahepatic bile duct resection locally advanced gallbladder carcinoma without extrahepatic bile duct invasion medical records retrospectively reviewed microvessel invasion mvi including lymphatic venous perineural invasions around extrahepatic bile duct results 52 patients 8 15 mvi around extrahepatic bile duct 8 patients stage iv disease according survival analysis 50 patients tolerated surgery mvis around extrahepatic bile duct distant metastasis identified independent prognostic factors survival patients mvi around extrahepatic bile duct dismal lack 2 year survivors conclusions mvi around extrahepatic bile duct sign extremely locally advanced gallbladder carcinoma therefore prophylactic combined bile duct resection survival impact patients without extrahepatic bile duct invasion pubmed","probabilities":0.9799733,"Title":"Combined extrahepatic bile duct resection for locally advanced gallbladder carcinoma: does it work?","Abstract":"BACKGROUND: Prophylactic combined extrahepatic bile duct resection remains controversial for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion. The aim of this study is to resolve this issue and establish an appropriate surgery for locally advanced gallbladder carcinoma. METHODS: A total of 52 patients underwent surgical resection combined with extrahepatic bile duct resection for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion, and their medical records were retrospectively reviewed for microvessel invasion (MVI), including lymphatic, venous, and/or perineural invasions, around the extrahepatic bile duct. RESULTS: Of the 52 patients, 8 (15 %) had MVI around the extrahepatic bile duct. All of the 8 patients had Stage IV disease. According to a survival analysis of the 50 patients who tolerated surgery, MVIs around the extrahepatic bile duct and distant metastasis were identified as independent prognostic factors. Survival for patients with MVI around the extrahepatic bile duct was dismal, with a lack of 2-year survivors. CONCLUSIONS: MVI around the extrahepatic bile duct is a sign of extremely locally advanced gallbladder carcinoma; therefore, prophylactic combined bile duct resection has no survival impact for patients without extrahepatic bile duct invasion.","Source":"PubMed","category":"HUMAN","training_data":"Combined extrahepatic bile duct resection for locally advanced gallbladder carcinoma: does it work? BACKGROUND: Prophylactic combined extrahepatic bile duct resection remains controversial for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion. The aim of this study is to resolve this issue and establish an appropriate surgery for locally advanced gallbladder carcinoma. METHODS: A total of 52 patients underwent surgical resection combined with extrahepatic bile duct resection for locally advanced gallbladder carcinoma without extrahepatic bile duct invasion, and their medical records were retrospectively reviewed for microvessel invasion (MVI), including lymphatic, venous, and/or perineural invasions, around the extrahepatic bile duct. RESULTS: Of the 52 patients, 8 (15 %) had MVI around the extrahepatic bile duct. All of the 8 patients had Stage IV disease. According to a survival analysis of the 50 patients who tolerated surgery, MVIs around the extrahepatic bile duct and distant metastasis were identified as independent prognostic factors. Survival for patients with MVI around the extrahepatic bile duct was dismal, with a lack of 2-year survivors. CONCLUSIONS: MVI around the extrahepatic bile duct is a sign of extremely locally advanced gallbladder carcinoma; therefore, prophylactic combined bile duct resection has no survival impact for patients without extrahepatic bile duct invasion. PubMed","prediction_labels":"HUMAN"},{"cleaned":"rhinacanthin c extracted rhinacanthus nasutus l inhibits cholangiocarcinoma cell migration invasion decreasing mmp 2 upa fak mapk pathways cholangiocarcinoma malignant tumor high metastatic mortality rates investigated effects rhinacanthin c cell proliferation migration invasion expression proteins regulating cancer cell invasion regulated proteins cholangiocarcinoma kku m156 cell line cytotoxicity rhinacanthin c determined srb assay using wound migration chamber migration chamber invasion assays assessed effects rhinacanthin c kku m156 cells activities matrix metalloproteinases 2 9 mmp 2 mmp 9 urokinase type plasminogen activator upa determined using gelatinase upa zymography assays expression invasion regulated proteins investigated using western blot analysis treatment rhinacanthin c kku m156 cells exhibited antiproliferative effects dose dependent manner greater efficacy vero cells ic50 values 1 50 2 37 m respectively rhinacanthin c significantly inhibited cell migration invasion kku m156 cells dose dependent manner consistent observation treatment rhinacanthin c associated decrease expression levels fak p fak mmp 2 decrease levels p38 jnk1 2 erk1 2 mapk pathways well inhibiting nf b p65 expression translocation nf b p65 nucleus shown first time anti metastatic effects rhinacanthin c kku m156 cells mediated via inhibition expression invasion regulated proteins rhinacanthin c may deserve consideration potential agent treatment cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Rhinacanthin-C Extracted From Rhinacanthus Nasutus (L) Inhibits Cholangiocarcinoma Cell Migration And Invasion By Decreasing Mmp-2 Upa Fak And Mapk Pathways","Abstract":"Cholangiocarcinoma is a malignant tumor with high metastatic and mortality rates. We investigated the effects of rhinacanthin-C on cell proliferation, migration, invasion and the expression of proteins regulating cancer cell invasion-regulated proteins in a cholangiocarcinoma (KKU-M156) cell line. Cytotoxicity of rhinacanthin-C was determined by the SRB assay. Using wound-migration, chamber-migration and chamber-invasion assays, we assessed the effects of rhinacanthin-C against KKU-M156 cells. The activities of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9) and urokinase-type plasminogen activator (uPA) were determined using gelatinase and uPA zymography assays. The expression of invasion-regulated proteins was investigated using western-blot analysis. After treatment with rhinacanthin-C, KKU-M156 cells exhibited antiproliferative effects in a dose-dependent manner with greater efficacy than in Vero cells: IC50 values were 1.50 and 2.37 μM, respectively. Rhinacanthin-C significantly inhibited cell migration and invasion of KKU-M156 cells in a dose-dependent manner. Consistent with this observation, treatment with rhinacanthin-C was associated with a decrease in the expression levels of FAK, p-FAK, MMP-2, and a decrease in the levels of p38-, JNK1/2- and ERK1/2-MAPK pathways as well as inhibiting NF-κB/p65 expression and translocation of NF-κB/p65 to the nucleus. We have shown for the first time that the anti-metastatic effects of rhinacanthin-C on KKU-M156 cells are mediated via inhibition of the expression of invasion-regulated proteins. Rhinacanthin-C may deserve consideration as a potential agent for the treatment of cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Rhinacanthin-C Extracted From Rhinacanthus Nasutus (L) Inhibits Cholangiocarcinoma Cell Migration And Invasion By Decreasing Mmp-2 Upa Fak And Mapk Pathways Cholangiocarcinoma is a malignant tumor with high metastatic and mortality rates. We investigated the effects of rhinacanthin-C on cell proliferation, migration, invasion and the expression of proteins regulating cancer cell invasion-regulated proteins in a cholangiocarcinoma (KKU-M156) cell line. Cytotoxicity of rhinacanthin-C was determined by the SRB assay. Using wound-migration, chamber-migration and chamber-invasion assays, we assessed the effects of rhinacanthin-C against KKU-M156 cells. The activities of matrix metalloproteinases 2 and 9 (MMP-2, MMP-9) and urokinase-type plasminogen activator (uPA) were determined using gelatinase and uPA zymography assays. The expression of invasion-regulated proteins was investigated using western-blot analysis. After treatment with rhinacanthin-C, KKU-M156 cells exhibited antiproliferative effects in a dose-dependent manner with greater efficacy than in Vero cells: IC50 values were 1.50 and 2.37 μM, respectively. Rhinacanthin-C significantly inhibited cell migration and invasion of KKU-M156 cells in a dose-dependent manner. Consistent with this observation, treatment with rhinacanthin-C was associated with a decrease in the expression levels of FAK, p-FAK, MMP-2, and a decrease in the levels of p38-, JNK1/2- and ERK1/2-MAPK pathways as well as inhibiting NF-κB/p65 expression and translocation of NF-κB/p65 to the nucleus. We have shown for the first time that the anti-metastatic effects of rhinacanthin-C on KKU-M156 cells are mediated via inhibition of the expression of invasion-regulated proteins. Rhinacanthin-C may deserve consideration as a potential agent for the treatment of cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"clinical value inflammation based prognostic scores predict resectability hyperbilirubinemia patients potentially resectable hilar cholangiocarcinoma background aimed examine whether inflammation based prognostic scores predict tumor resectability cohort hilar cholangiocarcinoma patients preoperative hyperbilirubinemia also sought investigate prognostic factors associated overall survival subgroup patients r0 resection methods total 173 patients potentially resectable hilar cholangiocarcinoma judged radiological examinations included potential relationship glasgow prognostic score gps modified gps platelet lymphocyte ratio plr neutrophil lymphocyte ratio nlr prognostic nutritional index pni prognostic index pi tumor resectability investigated using univariate multivariate analysis results among 173 patients 134 r0 resection margins univariate analysis identified patients plr 150 nlr 3 pni 45 gps 0 1 2 modified gps 0 1 2 preoperative ca 125 35 u ml tumor size 3 cm likely unresectable tumors multivariate analysis indicated tumor size 3 cm 2 422 95 ci 1 053 5 573 p 0 037 plr 150 3 324 95 ci 1 143 9 667 p 0 027 preoperative ca 125 35 u ml 3 184 95 ci 1 316 7 704 p 0 010 gps 0 1 2 2 440 95 ci 1 450 4 107 p 0 001 independent factors associated tumor resectability selected patients r0 resection cohort nodal status p 0 010 tumor differentiation p 0 025 predictive poor survival outcome conclusion patients higher gps ca 125 plr levels larger tumor size tend unresectable tumors even judged potentially resectable using preoperative radiological examinations pubmed","probabilities":0.9799733,"Title":"Clinical Value of Inflammation-Based Prognostic Scores to Predict the Resectability of Hyperbilirubinemia Patients with Potentially Resectable Hilar Cholangiocarcinoma","Abstract":"BACKGROUND: We aimed to examine whether inflammation-based prognostic scores could predict tumor resectability in a cohort of hilar cholangiocarcinoma patients with preoperative hyperbilirubinemia. We also sought to investigate the prognostic factors associated with overall survival in the subgroup of patients with an R0 resection. METHODS: A total of 173 patients with potentially resectable hilar cholangiocarcinoma, as judged by radiological examinations, were included. The potential relationship of the Glasgow prognostic score (GPS), modified GPS, platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), prognostic nutritional index (PNI), and prognostic index (PI) with tumor resectability were investigated using univariate and multivariate analysis. RESULTS: Among the 173 patients, 134 had R0 resection margins. Univariate analysis identified that patients with PLR ≥ 150, NLR ≥ 3, PNI ≥ 45, GPS (0.1/2), modified GPS (0.1/2), preoperative CA 125 > 35 U/mL, and a tumor size ≥ 3 cm were more likely to have unresectable tumors. Multivariate analysis indicated that tumor size ≥ 3 cm (OR = 2.422, 95% CI: 1.053-5.573; P = 0.037), PLR ≥ 150 (OR = 3.324, 95% CI: 1.143-9.667; P = 0.027), preoperative CA 125 > 35 U/mL (OR = 3.184, 95% CI: 1.316-7.704; P = 0.010), and GPS (0.1/2) (OR = 2.440, 95% CI: 1.450-4.107; P = 0.001) were independent factors associated with tumor resectability. In selected patients with an R0 resection in this cohort, nodal status (P = 0.010) and tumor differentiation (P = 0.025) were predictive of poor survival outcome. CONCLUSION: Patients with higher GPS, CA 125, and PLR levels, and a larger tumor size, tend to have unresectable tumors even if they were judged as potentially resectable using preoperative radiological examinations.","Source":"PubMed","category":"HUMAN","training_data":"Clinical Value of Inflammation-Based Prognostic Scores to Predict the Resectability of Hyperbilirubinemia Patients with Potentially Resectable Hilar Cholangiocarcinoma BACKGROUND: We aimed to examine whether inflammation-based prognostic scores could predict tumor resectability in a cohort of hilar cholangiocarcinoma patients with preoperative hyperbilirubinemia. We also sought to investigate the prognostic factors associated with overall survival in the subgroup of patients with an R0 resection. METHODS: A total of 173 patients with potentially resectable hilar cholangiocarcinoma, as judged by radiological examinations, were included. The potential relationship of the Glasgow prognostic score (GPS), modified GPS, platelet lymphocyte ratio (PLR), neutrophil lymphocyte ratio (NLR), prognostic nutritional index (PNI), and prognostic index (PI) with tumor resectability were investigated using univariate and multivariate analysis. RESULTS: Among the 173 patients, 134 had R0 resection margins. Univariate analysis identified that patients with PLR ≥ 150, NLR ≥ 3, PNI ≥ 45, GPS (0.1/2), modified GPS (0.1/2), preoperative CA 125 > 35 U/mL, and a tumor size ≥ 3 cm were more likely to have unresectable tumors. Multivariate analysis indicated that tumor size ≥ 3 cm (OR = 2.422, 95% CI: 1.053-5.573; P = 0.037), PLR ≥ 150 (OR = 3.324, 95% CI: 1.143-9.667; P = 0.027), preoperative CA 125 > 35 U/mL (OR = 3.184, 95% CI: 1.316-7.704; P = 0.010), and GPS (0.1/2) (OR = 2.440, 95% CI: 1.450-4.107; P = 0.001) were independent factors associated with tumor resectability. In selected patients with an R0 resection in this cohort, nodal status (P = 0.010) and tumor differentiation (P = 0.025) were predictive of poor survival outcome. CONCLUSION: Patients with higher GPS, CA 125, and PLR levels, and a larger tumor size, tend to have unresectable tumors even if they were judged as potentially resectable using preoperative radiological examinations. PubMed","prediction_labels":"HUMAN"},{"cleaned":"factors predicting adequate lymph node yield patients undergoing pancreatoduodenectomy malignancy background pancreatoduodenectomy resections meet minimum 12 lymph nodes recommended american joint committee cancer accurate staging periampullary malignancies purpose study investigate factors affecting likelihood adequate nodal yield pancreatoduodenectomy specimens subject routine pathological assessment methods six hundred sixty two patients subject pancreatoduodenectomy 1990 2013 pancreatic ampullary common bile duct cancers reviewed predictors yielding least 12 lymph nodes evaluated logistic regression model survival analysis carried verify prognostic implications nodal counts results median number evaluated nodes 17 interquartile range 11 25 less 12 lymph nodes reported surgical specimens 179 27 patients tumor diameter 20 mm odds ratio 2 547 95 confidence interval ci 1 225 5 329 p 0 013 lymph node metastases 2 642 95 ci 1 378 5 061 p 0 004 radical lymphadenectomy 5 566 95 ci 2 041 15 148 p 0 01 significant predictors retrieving 12 lymph nodes lymph node counts influence overall prognosis patients however subgroup analysis carried individual cancer sites demonstrated removing least 12 lymph nodes associated better prognosis pancreatic cancer conclusions variables affect adequate nodal yield pancreatoduodenectomy specimens subject routine pathological assessment considering ambiguities related modifiable factor identified appropriate pathology training considered increase nodal yield rather aggressive lymphatic dissection pubmed","probabilities":0.9799733,"Title":"Factors predicting adequate lymph node yield in patients undergoing pancreatoduodenectomy for malignancy","Abstract":"BACKGROUND: Most pancreatoduodenectomy resections do not meet the minimum of 12 lymph nodes recommended by the American Joint Committee on Cancer for accurate staging of periampullary malignancies. The purpose of this study was to investigate factors affecting the likelihood of adequate nodal yield in pancreatoduodenectomy specimens subject to routine pathological assessment. METHODS: Six hundred sixty-two patients subject to pancreatoduodenectomy between 1990 and 2013 for pancreatic, ampullary, and common bile duct cancers were reviewed. Predictors of yielding at least 12 lymph nodes were evaluated with a logistic regression model, and a survival analysis was carried out to verify the prognostic implications of nodal counts. RESULTS: The median number of evaluated nodes was 17 (interquartile range 11 to 25), and less than 12 lymph nodes were reported in surgical specimens of 179 (27 %) patients. Tumor diameter ≥20 mm (odds ratio [OR] 2.547, 95 % confidence interval [CI] 1.225 to 5.329, P = 0.013), lymph node metastases (OR 2.642, 95 % CI 1.378 to 5.061, P = 0.004), and radical lymphadenectomy (OR 5.566, 95 % CI 2.041 to 15.148, P = 0.01) were significant predictors of retrieving 12 or more lymph nodes. Lymph node counts did not influence the overall prognosis of the patients. However, a subgroup analysis carried out for individual cancer sites demonstrated that removing at least 12 lymph nodes is associated with better prognosis for pancreatic cancer. CONCLUSIONS: Few variables affect adequate nodal yield in pancreatoduodenectomy specimens subject to routine pathological assessment. Considering the ambiguities related to the only modifiable factor identified, appropriate pathology training should be considered to increase nodal yield rather than more aggressive lymphatic dissection.","Source":"PubMed","category":"HUMAN","training_data":"Factors predicting adequate lymph node yield in patients undergoing pancreatoduodenectomy for malignancy BACKGROUND: Most pancreatoduodenectomy resections do not meet the minimum of 12 lymph nodes recommended by the American Joint Committee on Cancer for accurate staging of periampullary malignancies. The purpose of this study was to investigate factors affecting the likelihood of adequate nodal yield in pancreatoduodenectomy specimens subject to routine pathological assessment. METHODS: Six hundred sixty-two patients subject to pancreatoduodenectomy between 1990 and 2013 for pancreatic, ampullary, and common bile duct cancers were reviewed. Predictors of yielding at least 12 lymph nodes were evaluated with a logistic regression model, and a survival analysis was carried out to verify the prognostic implications of nodal counts. RESULTS: The median number of evaluated nodes was 17 (interquartile range 11 to 25), and less than 12 lymph nodes were reported in surgical specimens of 179 (27 %) patients. Tumor diameter ≥20 mm (odds ratio [OR] 2.547, 95 % confidence interval [CI] 1.225 to 5.329, P = 0.013), lymph node metastases (OR 2.642, 95 % CI 1.378 to 5.061, P = 0.004), and radical lymphadenectomy (OR 5.566, 95 % CI 2.041 to 15.148, P = 0.01) were significant predictors of retrieving 12 or more lymph nodes. Lymph node counts did not influence the overall prognosis of the patients. However, a subgroup analysis carried out for individual cancer sites demonstrated that removing at least 12 lymph nodes is associated with better prognosis for pancreatic cancer. CONCLUSIONS: Few variables affect adequate nodal yield in pancreatoduodenectomy specimens subject to routine pathological assessment. Considering the ambiguities related to the only modifiable factor identified, appropriate pathology training should be considered to increase nodal yield rather than more aggressive lymphatic dissection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"biliary tract cancers associated risk venous thromboembolism background venous thromboembolism vte common cause morbidity mortality cancer patients biliary tract cancers btc cholangiocarcinoma gallbladder gb cancer uncommon incidence vte population well described methods conducted retrospective study patients btc identified cancer registry los angeles county university southern california usc medical center usc norris cancer center usc keck hospital january 2011 december 2016 describe incidence vte 330 btc patients medical records reviewed demographics tumor characteristics treatment history vte events 41 patients excluded due incomplete records follow overall survival os calculated date diagnosis date death last follow logrank test used evaluate association vte os results 289 patients btc identified 177 cholangiocarcinoma 112 gb median follow period 16 7 0 3 89 0 months mo 169 58 women median age diagnosis 66 years range 22 89 144 59 underwent cancer surgery 274 95 received chemotherapy 65 22 patients vte events 22 pulmonary embolism pe without lower extremity le deep vein thrombosis dvt 15 le dvt alone three upper extremity dvt 30 visceral thrombosis 27 portal vein thrombosis pvt without inferior vena cava thrombosis ivc 2 ivc thrombosis two hepatic vein thrombosis five patients dvt pe visceral thrombosis median time cancer diagnosis vte event met patients pvt visceral thrombosis inferior os compared without pvt median os 16 2 mo 95 ci 12 2 25 8 versus 7 5 3 4 14 2 p 0 10 visceral thrombosis 17 0 mo 95 ci 11 8 25 9 versus 8 4 95 ci 3 7 14 3 p 0 30 non significant trend towards inferior os patients vte event type median os 17 0 mo 95 ci 11 8 39 0 versus 11 4 95 ci 7 2 18 4 p 0 10 difference os patients pe dvt compared without conclusions vte commonly observed patients btc visceral thrombosis associated inferior survival patients btc google scholar","probabilities":0.9799733,"Title":"Biliary Tract Cancers And The Associated Risk Of Venous Thromboembolism","Abstract":"Background: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients. Because biliary tract cancers (BTC) cholangiocarcinoma and gallbladder (GB) cancer are uncommon, the incidence of VTE in this population are not well-described. Methods: We conducted a retrospective study of patients with BTC identified by the cancer registry at the Los Angeles County-University of Southern California (USC) Medical Center, USC Norris Cancer Center, and USC Keck Hospital between January 2011 to December 2016 to describe the incidence of VTE. 330 BTC patients’ medical records were reviewed for demographics, tumor characteristics, treatment history, and VTE events. 41 patients were excluded due to incomplete records/follow-up. Overall survival (OS) was calculated from date of diagnosis to date of death or last follow-up. Logrank test was used to evaluate the association of VTE with OS. Results: 289 patients with BTC were identified (177 cholangiocarcinoma, 112 GB) with a median follow-up period of 16.7 (0.3-89.0) months (mo). 169 (58%) were women. The median age at diagnosis of 66 years (range 22-89). 144 (59%) underwent cancer surgery and 274 (95%) received chemotherapy. 65 (22%) patients had VTE events: 22 pulmonary embolism [PE] with or without lower extremity (LE) deep vein thrombosis [DVT], 15 with LE DVT alone, three with upper extremity DVT, and 30 with visceral thrombosis (27 portal vein thrombosis [PVT] with or without inferior vena cava thrombosis [IVC], 2 IVC thrombosis, two hepatic vein thrombosis). Five patients had both DVT/PE and visceral thrombosis. The median time from cancer diagnosis to VTE event was not met. Patients with a PVT or any visceral thrombosis had an inferior OS compared to those without (PVT: median OS 16.2 mo [95% CI 12.2-25.8] versus 7.5 [3.4-14.2], p = 0.10, visceral thrombosis: 17.0 mo [95% CI 11.8-25.9] versus 8.4 [95% CI 3.7-14.3], p = 0.30). There was a non-significant trend towards inferior OS in patients with any VTE event type (median OS 17.0 mo [95% CI 11.8-39.0] versus 11.4 [95% CI 7.2-18.4], p = 0.10). There was no difference in OS for patients with PE/DVT compared to those without. Conclusions: VTE is commonly observed in patients with BTC. Visceral thrombosis is associated with inferior survival in patients with BTC.","Source":"Google Scholar","category":"HUMAN","training_data":"Biliary Tract Cancers And The Associated Risk Of Venous Thromboembolism Background: Venous thromboembolism (VTE) is a common cause of morbidity and mortality in cancer patients. Because biliary tract cancers (BTC) cholangiocarcinoma and gallbladder (GB) cancer are uncommon, the incidence of VTE in this population are not well-described. Methods: We conducted a retrospective study of patients with BTC identified by the cancer registry at the Los Angeles County-University of Southern California (USC) Medical Center, USC Norris Cancer Center, and USC Keck Hospital between January 2011 to December 2016 to describe the incidence of VTE. 330 BTC patients’ medical records were reviewed for demographics, tumor characteristics, treatment history, and VTE events. 41 patients were excluded due to incomplete records/follow-up. Overall survival (OS) was calculated from date of diagnosis to date of death or last follow-up. Logrank test was used to evaluate the association of VTE with OS. Results: 289 patients with BTC were identified (177 cholangiocarcinoma, 112 GB) with a median follow-up period of 16.7 (0.3-89.0) months (mo). 169 (58%) were women. The median age at diagnosis of 66 years (range 22-89). 144 (59%) underwent cancer surgery and 274 (95%) received chemotherapy. 65 (22%) patients had VTE events: 22 pulmonary embolism [PE] with or without lower extremity (LE) deep vein thrombosis [DVT], 15 with LE DVT alone, three with upper extremity DVT, and 30 with visceral thrombosis (27 portal vein thrombosis [PVT] with or without inferior vena cava thrombosis [IVC], 2 IVC thrombosis, two hepatic vein thrombosis). Five patients had both DVT/PE and visceral thrombosis. The median time from cancer diagnosis to VTE event was not met. Patients with a PVT or any visceral thrombosis had an inferior OS compared to those without (PVT: median OS 16.2 mo [95% CI 12.2-25.8] versus 7.5 [3.4-14.2], p = 0.10, visceral thrombosis: 17.0 mo [95% CI 11.8-25.9] versus 8.4 [95% CI 3.7-14.3], p = 0.30). There was a non-significant trend towards inferior OS in patients with any VTE event type (median OS 17.0 mo [95% CI 11.8-39.0] versus 11.4 [95% CI 7.2-18.4], p = 0.10). There was no difference in OS for patients with PE/DVT compared to those without. Conclusions: VTE is commonly observed in patients with BTC. Visceral thrombosis is associated with inferior survival in patients with BTC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"effects different anesthesia methods cellular immune function prognosis survival patients gallbladder carcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Effects Of Different Anesthesia Methods On Cellular Immune Function And Prognosis Survival Of Patients With Gallbladder Carcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Effects Of Different Anesthesia Methods On Cellular Immune Function And Prognosis Survival Of Patients With Gallbladder Carcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma risk factors environmental influences oncogenesis cholangiocarcinoma cca one frequent malignant epithelial liver tumors hepatocellular carcinoma hcc incidence seems increasing worldwide although risk factors heterogeneous differ globally although diagnostic therapeutic medicine advanced several countries tackling tumor remains challenge causes cca increasing incidence likely differential increment factors according geographical area considered review environment linked risk factors may play critical role carcinogenesis liver flukes may play major role east asia exposure chemical compounds naphthenic acids postulated source rate increase western countries carcinogenesis variable confounding factors also need taken account carcinogenesis depends sequential process probably involves cholestasis chronic inflammation promoting steps induction release interaction interleukin 6 il 6 transforming growth factor beta tgf beta tumor necrosis factor alpha tnf alpha platelet derived growth factor pdgf basis proliferation biliary epithelial cells cholangiocytes additional steps final development cca may also involve increase mutation rate tumor suppressor genes tp53 evasion apoptosis pubmed","probabilities":0.9799733,"Title":"Cholangiocarcinoma: risk factors, environmental influences and oncogenesis","Abstract":"Cholangiocarcinoma (CCA) is one of the most frequent malignant epithelial liver tumors after hepatocellular carcinoma (HCC). Its incidence seems to be increasing worldwide, although risk factors are heterogeneous and differ globally. Although diagnostic and therapeutic medicine have advanced in several countries, tackling this tumor remains a challenge. The causes of CCA's increasing incidence are likely a differential increment of some factors according to the geographical area, which will be considered in this review. Environment-linked risk factors may play a critical role in the carcinogenesis. Liver flukes may play a major role in East Asia, while exposure to chemical compounds, such as naphthenic acids, has been postulated as a source of the rate increase in Western countries. Carcinogenesis is variable and confounding factors also need to be taken into account. Carcinogenesis depends on a sequential process and most probably involves both cholestasis and chronic inflammation as promoting steps after induction. The release and interaction of interleukin-6 (IL-6), transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), and platelet-derived growth factor (PDGF) are at the basis of the proliferation of biliary epithelial cells or cholangiocytes. Additional steps for the final development of CCA may also involve an increase of the mutation rate of tumor suppressor genes, such as TP53, and the evasion of apoptosis.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma: risk factors, environmental influences and oncogenesis Cholangiocarcinoma (CCA) is one of the most frequent malignant epithelial liver tumors after hepatocellular carcinoma (HCC). Its incidence seems to be increasing worldwide, although risk factors are heterogeneous and differ globally. Although diagnostic and therapeutic medicine have advanced in several countries, tackling this tumor remains a challenge. The causes of CCA's increasing incidence are likely a differential increment of some factors according to the geographical area, which will be considered in this review. Environment-linked risk factors may play a critical role in the carcinogenesis. Liver flukes may play a major role in East Asia, while exposure to chemical compounds, such as naphthenic acids, has been postulated as a source of the rate increase in Western countries. Carcinogenesis is variable and confounding factors also need to be taken into account. Carcinogenesis depends on a sequential process and most probably involves both cholestasis and chronic inflammation as promoting steps after induction. The release and interaction of interleukin-6 (IL-6), transforming growth factor beta (TGF-beta), tumor necrosis factor alpha (TNF-alpha), and platelet-derived growth factor (PDGF) are at the basis of the proliferation of biliary epithelial cells or cholangiocytes. Additional steps for the final development of CCA may also involve an increase of the mutation rate of tumor suppressor genes, such as TP53, and the evasion of apoptosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence risk factors surveillance performance liver cancer patients alcoholic liver disease retrospective cohort analysis 5160 patients background alcohol increases risk liver cancer optimal strategy early cancer detection established patients alcoholic liver disease ald incidence high enough justify universal surveillance retrospective cohort study aimed investigate incidence risk factors development liver cancer ald patients regularly followed tertiary referral center addition performance liver ultrasound us alpha fetoprotein afp assessed detection liver cancer follow methods total 5 160 consecutive patients included study cohort diagnosed ald followed 6 months apr 2004 dec 2017 patients followed us without afp cohort randomly assigned 1 1 either derivation validation cohort risk factors liver cancer identi ed derivation cohort competing risk cox model nomogram developed accordingly r rms package performance nomogram assessed validation cohort diagnostic performance us afp analyzed receiver operating characteristic roc analysis results median follow 5 4 years total 153 patients newly diagnosed liver cancer estimated annual incidence 0 5 146 cases hcc 6 cases intrahepatic cholangiocarcinoma 1 case combined hepatocellular cholangiocarcinoma independent predictors included old age 60 years hazard ratio hr 2 35 95 ci 1 67 3 32 male hr 2 79 95 ci 1 57 4 95 diabetes hr 1 68 95 ci 1 20 2 34 cirrhosis hr 17 48 95 ci 9 51 32 13 low serum platelet count 130 000 mm3 hr 2 22 95 ci 1 54 3 18 high afp level 20ng ml hr 2 82 95 ci 1 61 4 94 positive serum hepatitis b surface antigen hbsag hr 2 08 95 ci 1 38 3 13 positive serum anti hcv antibody hr 2 07 95 ci 1 17 3 64 nomogram using independent risk factors differentiated risk development liver cancer hazard ratio 25 85 95 ci 13 20 50 62 cut 120 auc value liver us signi cantly higher afp cut 20ng ml 0 842 vs 0 558 respectively p 0 01 addition afp signi cant increase auc us p 0 19 conclusion male sex old age diabetes presence cirrhosis low platelet counts high serum afp positive viral markers independent risk factors liver cancer development patients ald risk factor based nomogram identi ed higher risk patients follow addition afp increase performance us detecting liver cancer ald patients google scholar","probabilities":0.9799733,"Title":"Incidence Risk Factors And Surveillance Performance Of Liver Cancer In Patients With Alcoholic Liver Disease: Retrospective Cohort Analysis Of 5160 Patients","Abstract":"Background: Alcohol increases the risk of liver cancer, but optimal strategy for early cancer detection has not been established in patients with alcoholic liver disease (ALD) because the incidence is not high enough to justify universal surveillance. This retrospective cohort study aimed to investigate the incidence and risk factors for the development of liver cancer in ALD patients who were regularly followed in a tertiary referral center. In addition, the performance of liver ultrasound (US) and alpha-fetoprotein (AFP) was assessed for the detection of liver cancer during follow-up. Methods: A total of 5,160 consecutive patients was included in the study cohort who were diagnosed as ALD and followed for more than 6 months from Apr 2004 to Dec 2017. Patients were followed with US with or without AFP. The cohort was randomly assigned 1: 1 to either derivation and validation cohort. Risk factors for liver cancer were identied from the derivation cohort by competing risk Cox model and a nomogram was developed accordingly by R rms package, and the performance of the nomogram was assessed in the validation cohort. Diagnostic performance of US and AFP was analyzed by receiver operating characteristic (ROC) analysis. Results: During a median follow-up of 5.4 years, a total of 153 patients were newly diagnosed as liver cancer with the estimated annual incidence of 0.5 %: 146 cases of HCC, 6 cases of Intrahepatic cholangiocarcinoma and 1 case of combined hepatocellular-cholangiocarcinoma. The independent predictors included old age (>60 years; Hazard ratio [HR], 2.35; 95% CI, 1.67-3.32), male (HR, 2.79; 95% CI, 1.57-4.95), diabetes (HR, 1.68; 95% CI, 1.20-2.34), cirrhosis (HR, 17.48; 95% CI, 9.51-32.13), low serum platelet count (<130,000/mm3; HR, 2.22; 95% CI, 1.54-3.18), high AFP level (>20ng/mL; HR, 2.82; 95% CI 1.61-4.94), positive serum Hepatitis B surface antigen (HBsAg) (HR, 2.08; 95% CI, 1.38-3.13), and positive serum anti-HCV antibody (HR, 2.07; 95% CI, 1.17-3.64). The nomogram using independent risk factors differentiated the risk of further development of liver cancer with the hazard ratio of 25.85 (95% CI, 13.20-50.62) at the cut-off of 120. The AUC value of liver US was signicantly higher than that of AFP (cut-off, 20ng/mL) (0.842 vs. 0.558, respectively; p<0.01). Addition of AFP did not signicant increase the AUC of US (p=0.19). Conclusion: Male sex, old age, diabetes, presence of cirrhosis, low platelet counts, high serum AFP, and positive viral markers were independent risk factors for liver cancer development in patients with ALD, and risk factor-based nomogram identied higher risk patients. During follow-up, addition of AFP did not increase the performance of US for detecting liver cancer in ALD patients","Source":"Google Scholar","category":"HUMAN","training_data":"Incidence Risk Factors And Surveillance Performance Of Liver Cancer In Patients With Alcoholic Liver Disease: Retrospective Cohort Analysis Of 5160 Patients Background: Alcohol increases the risk of liver cancer, but optimal strategy for early cancer detection has not been established in patients with alcoholic liver disease (ALD) because the incidence is not high enough to justify universal surveillance. This retrospective cohort study aimed to investigate the incidence and risk factors for the development of liver cancer in ALD patients who were regularly followed in a tertiary referral center. In addition, the performance of liver ultrasound (US) and alpha-fetoprotein (AFP) was assessed for the detection of liver cancer during follow-up. Methods: A total of 5,160 consecutive patients was included in the study cohort who were diagnosed as ALD and followed for more than 6 months from Apr 2004 to Dec 2017. Patients were followed with US with or without AFP. The cohort was randomly assigned 1: 1 to either derivation and validation cohort. Risk factors for liver cancer were identied from the derivation cohort by competing risk Cox model and a nomogram was developed accordingly by R rms package, and the performance of the nomogram was assessed in the validation cohort. Diagnostic performance of US and AFP was analyzed by receiver operating characteristic (ROC) analysis. Results: During a median follow-up of 5.4 years, a total of 153 patients were newly diagnosed as liver cancer with the estimated annual incidence of 0.5 %: 146 cases of HCC, 6 cases of Intrahepatic cholangiocarcinoma and 1 case of combined hepatocellular-cholangiocarcinoma. The independent predictors included old age (>60 years; Hazard ratio [HR], 2.35; 95% CI, 1.67-3.32), male (HR, 2.79; 95% CI, 1.57-4.95), diabetes (HR, 1.68; 95% CI, 1.20-2.34), cirrhosis (HR, 17.48; 95% CI, 9.51-32.13), low serum platelet count (<130,000/mm3; HR, 2.22; 95% CI, 1.54-3.18), high AFP level (>20ng/mL; HR, 2.82; 95% CI 1.61-4.94), positive serum Hepatitis B surface antigen (HBsAg) (HR, 2.08; 95% CI, 1.38-3.13), and positive serum anti-HCV antibody (HR, 2.07; 95% CI, 1.17-3.64). The nomogram using independent risk factors differentiated the risk of further development of liver cancer with the hazard ratio of 25.85 (95% CI, 13.20-50.62) at the cut-off of 120. The AUC value of liver US was signicantly higher than that of AFP (cut-off, 20ng/mL) (0.842 vs. 0.558, respectively; p<0.01). Addition of AFP did not signicant increase the AUC of US (p=0.19). Conclusion: Male sex, old age, diabetes, presence of cirrhosis, low platelet counts, high serum AFP, and positive viral markers were independent risk factors for liver cancer development in patients with ALD, and risk factor-based nomogram identied higher risk patients. During follow-up, addition of AFP did not increase the performance of US for detecting liver cancer in ALD patients Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"body mass index biliary tract disease systematic review meta analysis prospective studies objective evaluate association body mass index bmi kg m 2 incidence biliary tract disease methods performed systematic review meta analysis prospective studies searching database pubmed embase published december 31 2013 outcome interest disease biliary tract system gallbladder extrahepatic bile duct ampullar vater used random effects model combine study specific relative risks rrs 95 confidence intervals 95 cis 22 prospective studies examined whether bmi associated higher risk biliary tract disease combined analysis results positive association stronger non cancer biliary tract disease biliary tract cancer combined rrs 95 cis comparing top bottom categories 1 40 1 15 1 65 biliary tract cancer 2 75 2 35 3 15 non cancer biliary tract disease p difference 0 001 non cancer biliary tract disease combined rrs 95 cis comparing top bottom categories 3 21 2 48 3 93 women 2 01 1 66 2 37 men p difference 0 04 conclusion obesity associated higher risks biliary tract cancer greater extent non cancer biliary tract disease pubmed","probabilities":0.9799733,"Title":"Body mass index and biliary tract disease: a systematic review and meta-analysis of prospective studies","Abstract":"OBJECTIVE: To evaluate the association between body mass index (BMI, kg/m(2)) and incidence of biliary tract disease. METHODS: We performed a systematic review and a meta-analysis of prospective studies by searching the database of PubMed and EMBASE published up to December 31, 2013. Outcome of interest was disease of biliary tract system (gallbladder, extrahepatic bile duct and Ampullar of Vater). We used a random-effects model to combine the study-specific relative risks (RRs) and 95% confidence intervals (95% CIs) from 22 prospective studies. We examined whether BMI was associated with a higher risk of biliary tract disease in a combined analysis. RESULTS: The positive association was stronger for non-cancer biliary tract disease than biliary tract cancer; combined RRs (95% CIs) comparing the top with bottom categories were 1.40 (1.15-1.65) for biliary tract cancer and 2.75 (2.35-3.15) for non-cancer biliary tract disease (P for difference<0.001). For non-cancer biliary tract disease, combined RRs (95% CIs) comparing the top with bottom categories were 3.21 (2.48-3.93) for women and 2.01 (1.66-2.37) for men (P for difference=0.04). CONCLUSION: Obesity is associated with higher risks of biliary tract cancer and, to a greater extent, non-cancer biliary tract disease.","Source":"PubMed","category":"HUMAN","training_data":"Body mass index and biliary tract disease: a systematic review and meta-analysis of prospective studies OBJECTIVE: To evaluate the association between body mass index (BMI, kg/m(2)) and incidence of biliary tract disease. METHODS: We performed a systematic review and a meta-analysis of prospective studies by searching the database of PubMed and EMBASE published up to December 31, 2013. Outcome of interest was disease of biliary tract system (gallbladder, extrahepatic bile duct and Ampullar of Vater). We used a random-effects model to combine the study-specific relative risks (RRs) and 95% confidence intervals (95% CIs) from 22 prospective studies. We examined whether BMI was associated with a higher risk of biliary tract disease in a combined analysis. RESULTS: The positive association was stronger for non-cancer biliary tract disease than biliary tract cancer; combined RRs (95% CIs) comparing the top with bottom categories were 1.40 (1.15-1.65) for biliary tract cancer and 2.75 (2.35-3.15) for non-cancer biliary tract disease (P for difference<0.001). For non-cancer biliary tract disease, combined RRs (95% CIs) comparing the top with bottom categories were 3.21 (2.48-3.93) for women and 2.01 (1.66-2.37) for men (P for difference=0.04). CONCLUSION: Obesity is associated with higher risks of biliary tract cancer and, to a greater extent, non-cancer biliary tract disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"determining adequate examined lymph node count resected ampullary adenocarcinoma national cohort study background evaluation lymph node involvement essential component cancer staging examining inadequate number lymph nodes potentially results understaging current guidelines lymph node retrieval ampullary adenocarcinoma based data extrapolated periampullary malignancies may applicable aim study determine number lymph nodes examined resection specimens optimize staging ampullary adenocarcinoma methods patients ampullary adenocarcinoma 2004 2014 identified national cancer database determined minimum examined lymph node eln count modeling potential eln count 2 30 multivariable regression analysis confirmed results sensitivity analysis results identified 7451 patients 52 2 t3 t4 disease 51 4 lymph node metastases median eln count 13 interquartile range 8 19 increasing elns independently associated increased likelihood positive nodal disease odds ratio 1 03 95 confidence interval ci 1 03 1 04 improved overall survival node negative hazard ratio hr 0 98 95 ci 0 97 0 99 node positive patients hr 0 99 95 ci 0 986 0 998 determined least 17 lymph nodes examined overall survival patients 17 elns superior fewer 17 elns conclusion increasing elns independently associated improved overall survival patients resected ampullary adenocarcinoma least 17 lymph nodes examined optimal nodal staging pubmed","probabilities":0.9799733,"Title":"Determining the Adequate Examined Lymph Node Count in Resected Ampullary Adenocarcinoma-A National Cohort Study","Abstract":"BACKGROUND: The evaluation of lymph node involvement is an essential component of cancer staging. Examining an inadequate number of lymph nodes potentially results in understaging. Current guidelines for lymph node retrieval for ampullary adenocarcinoma are based on data extrapolated from other periampullary malignancies and may not be applicable. The aim of this study was to determine the number of lymph nodes that should be examined in resection specimens to optimize staging in ampullary adenocarcinoma. METHODS: Patients with ampullary adenocarcinoma from 2004 to 2014 were identified in the National Cancer Database. We determined the minimum examined lymph node (ELN) count by modeling each potential ELN count from 2 to 30 in a multivariable regression analysis and confirmed the results with a sensitivity analysis. RESULTS: We identified 7451 patients of whom 52.2% had T3 or T4 disease and 51.4% had lymph node metastases. The median ELN count was 13 (interquartile range, 8-19). Increasing ELNs were independently associated with an increased likelihood of having positive nodal disease (odds ratio, 1.03; 95% confidence interval [CI], 1.03-1.04) and improved overall survival in both node-negative (hazard ratio [HR], 0.98; 95% CI, 0.97-0.99) and node-positive patients (HR, 0.99; 95% CI, 0.986-0.998). We determined that at least 17 lymph nodes should be examined. Overall survival for patients with 17 or more ELNs was superior than for those with fewer than 17 ELNs. CONCLUSION: Increasing ELNs were independently associated with improved overall survival in patients with resected ampullary adenocarcinoma. At least 17 lymph nodes should be examined for optimal nodal staging.","Source":"PubMed","category":"HUMAN","training_data":"Determining the Adequate Examined Lymph Node Count in Resected Ampullary Adenocarcinoma-A National Cohort Study BACKGROUND: The evaluation of lymph node involvement is an essential component of cancer staging. Examining an inadequate number of lymph nodes potentially results in understaging. Current guidelines for lymph node retrieval for ampullary adenocarcinoma are based on data extrapolated from other periampullary malignancies and may not be applicable. The aim of this study was to determine the number of lymph nodes that should be examined in resection specimens to optimize staging in ampullary adenocarcinoma. METHODS: Patients with ampullary adenocarcinoma from 2004 to 2014 were identified in the National Cancer Database. We determined the minimum examined lymph node (ELN) count by modeling each potential ELN count from 2 to 30 in a multivariable regression analysis and confirmed the results with a sensitivity analysis. RESULTS: We identified 7451 patients of whom 52.2% had T3 or T4 disease and 51.4% had lymph node metastases. The median ELN count was 13 (interquartile range, 8-19). Increasing ELNs were independently associated with an increased likelihood of having positive nodal disease (odds ratio, 1.03; 95% confidence interval [CI], 1.03-1.04) and improved overall survival in both node-negative (hazard ratio [HR], 0.98; 95% CI, 0.97-0.99) and node-positive patients (HR, 0.99; 95% CI, 0.986-0.998). We determined that at least 17 lymph nodes should be examined. Overall survival for patients with 17 or more ELNs was superior than for those with fewer than 17 ELNs. CONCLUSION: Increasing ELNs were independently associated with improved overall survival in patients with resected ampullary adenocarcinoma. At least 17 lymph nodes should be examined for optimal nodal staging. PubMed","prediction_labels":"HUMAN"},{"cleaned":"floxuridine hepatic arterial infusion associated biliary toxicity increased concurrent administration systemic bevacizumab purpose systemic bevacizumab bev added hepatic arterial infusion hai floxuridine fudr based chemotherapy three studies attempt improve outcomes specific review biliary toxicity carried methods analysis included 203 patients three prospective studies first study adjuvant study liver resection colorectal metastases patients received hai systemic chemotherapy sys without bev study b comprised unresectable colorectal patients received hai sys plus bev study c included patients unresectable cholangiocarcinoma hepatocellular carcinoma received hai plus systematic bev outcome toxicity patients studies b c compared historical controls results three studies incidence hyperbilirubinemia biliary stent placement within 1 year treatment increased addition bev bev versus bev groups placement biliary stents follows study 0 38 versus 4 35 patients p 0 05 study b 0 49 versus 3 24 p 0 06 study c 0 34 versus 3 22 p 0 15 elevation bilirubin noted bev versus bev groups study 0 38 versus 5 35 patients p 0 02 study b 1 49 versus 7 24 p 0 005 study c 2 34 versus 5 22 p 0 10 addition bev seem associated improved progression free overall survival conclusions addition bev hai fudr resulted increased biliary toxicity three separate studies although sample sizes small evidence improved pfs os addition bev bev combined hai fudr pubmed","probabilities":0.9799733,"Title":"Floxuridine hepatic arterial infusion associated biliary toxicity is increased by concurrent administration of systemic bevacizumab","Abstract":"PURPOSE: Systemic bevacizumab (Bev) was added to hepatic arterial infusion (HAI) floxuridine (FUDR)-based chemotherapy in three studies in an attempt to improve outcomes. A specific review of biliary toxicity was carried out. METHODS: This analysis included 203 patients from three prospective studies. The first (study A) was an adjuvant study after liver resection of colorectal metastases in which patients received HAI and systemic chemotherapy (Sys) with or without Bev. Study B comprised unresectable colorectal patients who received HAI and Sys plus Bev. Study C included patients with unresectable cholangiocarcinoma or hepatocellular carcinoma who received HAI plus systematic Bev. The outcome and toxicity of patients in studies B and C were compared with historical controls. RESULTS: In all three studies, the incidence of hyperbilirubinemia and biliary stent placement within 1 year of treatment was increased with the addition of Bev. In the no-Bev versus Bev groups, the placement of biliary stents was as follows: study A, 0 of 38 versus 4 of 35 patients (p = 0.05); study B, 0 of 49 versus 3 of 24 (p = 0.06); and study C, 0 of 34 versus 3 of 22 (p = 0.15). Elevation in bilirubin was noted in the no-Bev versus Bev groups: study A, 0 of 38 versus 5 of 35 patients (p = 0.02); study B, 1 of 49 versus 7 of 24 (p = 0.005); and study C, 2 of 34 versus 5 of 22 (p = 0.10). The addition of Bev did not seem to be associated with improved progression-free or overall survival. CONCLUSIONS: The addition of Bev to HAI FUDR resulted in increased biliary toxicity in three separate studies. Although the sample sizes were small, there was no evidence of improved PFS or OS with the addition of Bev. Bev should not be combined with HAI FUDR.","Source":"PubMed","category":"HUMAN","training_data":"Floxuridine hepatic arterial infusion associated biliary toxicity is increased by concurrent administration of systemic bevacizumab PURPOSE: Systemic bevacizumab (Bev) was added to hepatic arterial infusion (HAI) floxuridine (FUDR)-based chemotherapy in three studies in an attempt to improve outcomes. A specific review of biliary toxicity was carried out. METHODS: This analysis included 203 patients from three prospective studies. The first (study A) was an adjuvant study after liver resection of colorectal metastases in which patients received HAI and systemic chemotherapy (Sys) with or without Bev. Study B comprised unresectable colorectal patients who received HAI and Sys plus Bev. Study C included patients with unresectable cholangiocarcinoma or hepatocellular carcinoma who received HAI plus systematic Bev. The outcome and toxicity of patients in studies B and C were compared with historical controls. RESULTS: In all three studies, the incidence of hyperbilirubinemia and biliary stent placement within 1 year of treatment was increased with the addition of Bev. In the no-Bev versus Bev groups, the placement of biliary stents was as follows: study A, 0 of 38 versus 4 of 35 patients (p = 0.05); study B, 0 of 49 versus 3 of 24 (p = 0.06); and study C, 0 of 34 versus 3 of 22 (p = 0.15). Elevation in bilirubin was noted in the no-Bev versus Bev groups: study A, 0 of 38 versus 5 of 35 patients (p = 0.02); study B, 1 of 49 versus 7 of 24 (p = 0.005); and study C, 2 of 34 versus 5 of 22 (p = 0.10). The addition of Bev did not seem to be associated with improved progression-free or overall survival. CONCLUSIONS: The addition of Bev to HAI FUDR resulted in increased biliary toxicity in three separate studies. Although the sample sizes were small, there was no evidence of improved PFS or OS with the addition of Bev. Bev should not be combined with HAI FUDR. PubMed","prediction_labels":"HUMAN"},{"cleaned":"stage significant factor determining extent surgery gallbladder cancer background aims stage currently factor determining extent surgery gallbladder cancer gbca hypothesized perineural invasion another predictive factor determining extent surgery powerful prognostic factor gbca methodology retrospective analysis carried patients underwent operation gallbladder cancer february 1991 november 2011 data retrospectively analyzed reviewed microscopic findings checked pathologist result simple extended cholecystectomy performed 82 patients study period univariate analysis ca 19 9 level gross type depth invasion lymph node metastasis distant metastasis perineural invasion lymphatic invasion vascular invasion associated survival p 0 05 multivariate analysis perineural invasion vascular invasion impact survival p 0 05 conclusions n stage powerful prognostic factor gbca perineural invasion vascular invasion also significant prognostic factors improve survival radical resection considered early gbca perineural vascular invasion pubmed","probabilities":0.9799733,"Title":"Is T-stage the only significant factor determining the extent of surgery for gallbladder cancer?","Abstract":"BACKGROUND/AIMS: T-stage is currently the only factor determining the extent of surgery of gallbladder cancer (GBCA). We hypothesized that perineural invasion could be another predictive factor determining the extent of surgery because it is very powerful prognostic factor for GBCA. METHODOLOGY: A retrospective analysis was carried out of patients who underwent operation for gallbladder cancer between February 1991 and November 2011. The data were retrospectively analyzed and reviewed and the microscopic findings were checked by a pathologist. RESULT: Simple and extended cholecystectomy was performed in 82 patients during the study period. In univariate analysis, CA 19-9 level, gross type, depth of invasion, lymph node metastasis, distant metastasis, perineural invasion, lymphatic invasion and vascular invasion were associated with survival (P < 0.05). In multivariate analysis, perineural invasion and vascular invasion had an impact on survival (P < 0.05). CONCLUSIONS: T and N stage are powerful prognostic factor for GBCA, but perineural invasion and vascular invasion are also significant prognostic factors. To improve survival radical resection should be considered in early GBCA with perineural and vascular invasion.","Source":"PubMed","category":"HUMAN","training_data":"Is T-stage the only significant factor determining the extent of surgery for gallbladder cancer? BACKGROUND/AIMS: T-stage is currently the only factor determining the extent of surgery of gallbladder cancer (GBCA). We hypothesized that perineural invasion could be another predictive factor determining the extent of surgery because it is very powerful prognostic factor for GBCA. METHODOLOGY: A retrospective analysis was carried out of patients who underwent operation for gallbladder cancer between February 1991 and November 2011. The data were retrospectively analyzed and reviewed and the microscopic findings were checked by a pathologist. RESULT: Simple and extended cholecystectomy was performed in 82 patients during the study period. In univariate analysis, CA 19-9 level, gross type, depth of invasion, lymph node metastasis, distant metastasis, perineural invasion, lymphatic invasion and vascular invasion were associated with survival (P < 0.05). In multivariate analysis, perineural invasion and vascular invasion had an impact on survival (P < 0.05). CONCLUSIONS: T and N stage are powerful prognostic factor for GBCA, but perineural invasion and vascular invasion are also significant prognostic factors. To improve survival radical resection should be considered in early GBCA with perineural and vascular invasion. PubMed","prediction_labels":"HUMAN"},{"cleaned":"chronic heavy metal exposure gallbladder cancer risk india comparative study japan background high incidence gallbladder cancer gbc reported north india elevated concentrations heavy metals water soil indo japan collaborative study compared presence heavy metals gallbladder tissues methods heavy metal concentrations estimated indian gbc cholecystitis tissues compared japanese gbc cholecystitis tissues spectrophotometry done 13 indian gallbladder tissues 8 gbc 5 cholecystitis 9 japanese 5 gbc 4 cholecystitis transmission electron microscopy tem thin foil element analysis done 10 indian samples 6 gbc 4 cholecystitis results chromium lead arsenic zinc significantly high indian gbc compared japanese gbc chromium lead arsenic significantly high indian cholecystitis tissues compared japanese tem indian tissues demonstrated electron dense deposits gbc conclusion heavy metals chromium lead arsenic zinc potential carcinogens indian gbc endemic areas preliminary study links presence heavy metals gallbladder cancer tissues endemic areas stn","probabilities":0.88235295,"Title":"Chronic Heavy Metal Exposure And Gallbladder Cancer Risk In India A Comparative Study With Japan","Abstract":"Background: High incidence of gallbladder cancer (GBC) is reported from North India, with elevated concentrations of heavy metals in water and soil. This Indo-Japan collaborative study compared presence of heavy metals in gallbladder tissues. \r\n\r\n Methods: Heavy metal concentrations were estimated in Indian GBC and cholecystitis tissues and compared with Japanese GBC and cholecystitis tissues. Spectrophotometry was done for 13 Indian gallbladder tissues (8 GBC, 5 cholecystitis) and 9 Japanese (5 GBC, 4 cholecystitis). Transmission electron microscopy (TEM) thin foil element analysis was done in 10 Indian samples (6 GBC, 4 cholecystitis). \r\n\r\n Results: Chromium, lead, arsenic and zinc were significantly high in Indian GBC compared with Japanese GBC. Chromium, lead and arsenic were significantly high in the Indian cholecystitis tissues compared to the Japanese. TEM of Indian tissues demonstrated electron dense deposits in GBC. \r\n\r\n Conclusion: Heavy metals- chromium, lead, arsenic and zinc are potential carcinogens in Indian GBC from endemic areas. This preliminary study links presence of heavy metals in gallbladder cancer tissues in endemic areas.","Source":"STN","category":"HUMAN","training_data":"Chronic Heavy Metal Exposure And Gallbladder Cancer Risk In India A Comparative Study With Japan Background: High incidence of gallbladder cancer (GBC) is reported from North India, with elevated concentrations of heavy metals in water and soil. This Indo-Japan collaborative study compared presence of heavy metals in gallbladder tissues. \r\n\r\n Methods: Heavy metal concentrations were estimated in Indian GBC and cholecystitis tissues and compared with Japanese GBC and cholecystitis tissues. Spectrophotometry was done for 13 Indian gallbladder tissues (8 GBC, 5 cholecystitis) and 9 Japanese (5 GBC, 4 cholecystitis). Transmission electron microscopy (TEM) thin foil element analysis was done in 10 Indian samples (6 GBC, 4 cholecystitis). \r\n\r\n Results: Chromium, lead, arsenic and zinc were significantly high in Indian GBC compared with Japanese GBC. Chromium, lead and arsenic were significantly high in the Indian cholecystitis tissues compared to the Japanese. TEM of Indian tissues demonstrated electron dense deposits in GBC. \r\n\r\n Conclusion: Heavy metals- chromium, lead, arsenic and zinc are potential carcinogens in Indian GBC from endemic areas. This preliminary study links presence of heavy metals in gallbladder cancer tissues in endemic areas. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance neutrophil lymphocyte ratio sbrt cholangiocellular carcinoma purpose objective analysis evaluated prognostic significance neutrophil lymphocyte ratio nlr patients treated stereotactic body radiation therapy sbrt cholangiocellular carcinomas material methods consecutive patients n 26 histologically confirmed cholangiocellular carcinoma treated sbrt 2007 2017 included analysis majority patients treated local recurrence primary therapy primary therapy operative treatment option patients received median total dose 50 range 21 66 gy 3 12 fractions results median survival 14 months overall survival os 1 year sbrt 61 median progression free survival pfs 13 months 51 1 year local control 72 1 year median nlr 3 range 2 10 median crp 15 3 96 mg l median bilirubin 1 1 22 mg dl median ldh 233 156462 u l os correlate significantly nlr hr 1 231 95 ci 0 992 1 572 p 0 059 neither correlated nlr median 18 vs 14 months p 0 34 furthermore correlation shown crp ldh bilirubin overall survival conclusion analysis correlation demonstrated nlr survival patients cholangiocellular carcinoma treated sbrt google scholar","probabilities":0.9799733,"Title":"The Prognostic Significance Of Neutrophil /Lymphocyte Ratio For Sbrt Of Cholangiocellular Carcinoma","Abstract":"Purpose or Objective In this analysis, we evaluated the prognostic significance of the neutrophil / lymphocyte ratio (NLR) in patients treated with stereotactic body radiation therapy (SBRT) for cholangiocellular carcinomas. Material and Methods Consecutive patients (n = 26) with histologically confirmed cholangiocellular carcinoma who were treated with SBRT between 2007 and 2017 are included in this analysis. The majority of patients were treated for local recurrence after primary therapy or as primary therapy because there was no operative treatment option. Patients received a median total dose of 50 (range 21-66) Gy in 3-12 fractions. Results Median survival was 14 months with overall survival (OS) 1 year after SBRT of 61% with median progression-free survival (PFS) at 13 months and 51% at 1 year. The local control was 72% after 1 year. The median NLR was 3 (range 2-10) with a median CRP of 15 (3-96) mg / L with a median bilirubin of 1 (1-22) mg / dL and a median LDH of 233 (156462) U / l. The OS did not correlate significantly with the NLR (HR 1.231, 95% CI 0.992-1.572, p = 0.059) neither was it correlated with NLR above the median (18 vs 14 months, p = 0.34). Furthermore, no correlation could be shown between CRP, LDH or bilirubin with overall Survival. Conclusion In this analysis, no correlation could be demonstrated between NLR and survival in patients with cholangiocellular carcinoma treated with SBRT.","Source":"Google Scholar","category":"HUMAN","training_data":"The Prognostic Significance Of Neutrophil /Lymphocyte Ratio For Sbrt Of Cholangiocellular Carcinoma Purpose or Objective In this analysis, we evaluated the prognostic significance of the neutrophil / lymphocyte ratio (NLR) in patients treated with stereotactic body radiation therapy (SBRT) for cholangiocellular carcinomas. Material and Methods Consecutive patients (n = 26) with histologically confirmed cholangiocellular carcinoma who were treated with SBRT between 2007 and 2017 are included in this analysis. The majority of patients were treated for local recurrence after primary therapy or as primary therapy because there was no operative treatment option. Patients received a median total dose of 50 (range 21-66) Gy in 3-12 fractions. Results Median survival was 14 months with overall survival (OS) 1 year after SBRT of 61% with median progression-free survival (PFS) at 13 months and 51% at 1 year. The local control was 72% after 1 year. The median NLR was 3 (range 2-10) with a median CRP of 15 (3-96) mg / L with a median bilirubin of 1 (1-22) mg / dL and a median LDH of 233 (156462) U / l. The OS did not correlate significantly with the NLR (HR 1.231, 95% CI 0.992-1.572, p = 0.059) neither was it correlated with NLR above the median (18 vs 14 months, p = 0.34). Furthermore, no correlation could be shown between CRP, LDH or bilirubin with overall Survival. Conclusion In this analysis, no correlation could be demonstrated between NLR and survival in patients with cholangiocellular carcinoma treated with SBRT. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"effect epcam cd44 cd133 cd166 expression patient survival tumours ampulla vater background carcinomas vaterian system rare presumably arise pre existing adenomas according cancer stem cell csc hypothesis small subset tumor cells ability initiate develop tumor growth colorectal cancer cd44 cd133 cd166 epcam proposed represent csc marker proteins expression shown correlate patient survival aims evaluate potential role csc proteins tumors ampulla vater investigated expression 175 carcinoma 111 adenoma 152 normal mucosa specimens arranged tissue microarray format materials methods membranous immunoreactivity protein marker scored semi quantitatively evaluating number positive tumor cells total number tumor cells median protein expression levels used cut scores define protein marker positivity clinical data including survival time obtained retrospective analysis medical records tumor registries direct contact results expression evaluated marker proteins differed significantly normal mucosa adenoma carcinoma samples markers found tendency towards constant expression normal neoplastic tissue epcam expression significantly correlated better patient survival increased expression cd44s cd166 cd133 normal mucosa samples adenoma carcinoma linked tumor progression however statistically significant correlation survival conclusion findings indicate ampullary carcinomas loss expression epcam may linked aggressive tumor phenotype pubmed","probabilities":1.0,"Title":"Effect of EpCAM, CD44, CD133 and CD166 expression on patient survival in tumours of the ampulla of Vater","Abstract":"BACKGROUND: Carcinomas of the Vaterian system are rare and presumably arise from pre-existing adenomas. According to the cancer stem cell (CSC) hypothesis, only a small subset of tumor cells has the ability to initiate and develop tumor growth. In colorectal cancer, CD44, CD133, CD166 and EpCAM have been proposed to represent CSC marker proteins and their expression has been shown to correlate with patient survival. AIMS: To evaluate a potential role of these CSC proteins in tumors of the ampulla of Vater, we investigated their expression in 175 carcinoma, 111 adenoma and 152 normal mucosa specimens arranged in a Tissue Microarray format. MATERIALS AND METHODS: Membranous immunoreactivity for each protein marker was scored semi-quantitatively by evaluating the number of positive tumor cells over the total number of tumor cells. Median protein expression levels were used as cut-off scores to define protein marker positivity. Clinical data including survival time were obtained by retrospective analysis of medical records, tumor registries or direct contact. RESULTS: The expression of all evaluated marker proteins differed significantly between normal mucosa, adenoma and carcinoma samples. In all markers, we found a tendency towards more constant expression from normal to neoplastic tissue. EpCAM expression was significantly correlated with better patient survival. The increased expression of CD44s, CD166 and CD133 from normal mucosa samples to adenoma and carcinoma was linked to tumor progression. However, there was no statistically significant correlation with survival. CONCLUSION: Our findings indicate, that in ampullary carcinomas, loss of expression of EpCAM may be linked to a more aggressive tumor phenotype.","Source":"PubMed","category":"ANIMAL","training_data":"Effect of EpCAM, CD44, CD133 and CD166 expression on patient survival in tumours of the ampulla of Vater BACKGROUND: Carcinomas of the Vaterian system are rare and presumably arise from pre-existing adenomas. According to the cancer stem cell (CSC) hypothesis, only a small subset of tumor cells has the ability to initiate and develop tumor growth. In colorectal cancer, CD44, CD133, CD166 and EpCAM have been proposed to represent CSC marker proteins and their expression has been shown to correlate with patient survival. AIMS: To evaluate a potential role of these CSC proteins in tumors of the ampulla of Vater, we investigated their expression in 175 carcinoma, 111 adenoma and 152 normal mucosa specimens arranged in a Tissue Microarray format. MATERIALS AND METHODS: Membranous immunoreactivity for each protein marker was scored semi-quantitatively by evaluating the number of positive tumor cells over the total number of tumor cells. Median protein expression levels were used as cut-off scores to define protein marker positivity. Clinical data including survival time were obtained by retrospective analysis of medical records, tumor registries or direct contact. RESULTS: The expression of all evaluated marker proteins differed significantly between normal mucosa, adenoma and carcinoma samples. In all markers, we found a tendency towards more constant expression from normal to neoplastic tissue. EpCAM expression was significantly correlated with better patient survival. The increased expression of CD44s, CD166 and CD133 from normal mucosa samples to adenoma and carcinoma was linked to tumor progression. However, there was no statistically significant correlation with survival. CONCLUSION: Our findings indicate, that in ampullary carcinomas, loss of expression of EpCAM may be linked to a more aggressive tumor phenotype. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"neoadjuvant chemotherapy initially unresectable intrahepatic cholangiocarcinoma background locoregional extension intrahepatic cholangiocarcinoma icc time diagnosis results low resectability rate poor prognosis aim retrospective study assess efficacy neoadjuvant chemotherapy locally advanced icc methods consecutive patients icc 2000 2013 included prospectively single centre database analysed retrospectively patients locally advanced icc considered initially unresectable received primary chemotherapy followed surgery secondary resectability results patients underwent surgery locally advanced icc compared patients initially resectable icc treated surgery alone results total 186 patients included study 74 patients locally advanced icc 39 53 per cent underwent secondary resection median six chemotherapy cycles patients group younger p 0 030 advanced disease surgery alone presented frequently lymphadenopathy p 0 010 vascular invasion p 0 010 postoperative morbidity mortality different groups median survival patients surgery chemotherapy 24 1 months patients surgery alone 25 7 months p 0 391 conclusion patients locally advanced icc treated surgery following neoadjuvant chemotherapy similar short long term results patients initially resectable icc surgery alone neoadjuvant chemotherapy first line treatment locally advanced icc may effective downstaging option facilitating secondary resectability patients initially unresectable disease pubmed","probabilities":0.9799733,"Title":"Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Locoregional extension of intrahepatic cholangiocarcinoma (ICC) at the time of diagnosis results in a low resectability rate and poor prognosis. The aim of this retrospective study was to assess the efficacy of neoadjuvant chemotherapy for locally advanced ICC. METHODS: All consecutive patients with ICC between 2000 and 2013 were included prospectively in a single-centre database and analysed retrospectively. Patients with locally advanced ICC considered as initially unresectable received primary chemotherapy, followed by surgery in those with secondary resectability. Results of patients who underwent surgery for locally advanced ICC were compared with those of patients with initially resectable ICC treated by surgery alone. RESULTS: A total of 186 patients were included in the study. Of 74 patients with locally advanced ICC, 39 (53 per cent) underwent secondary resection after a median of six chemotherapy cycles. Patients in this group were younger (P = 0·030) and had more advanced disease than those who had surgery alone, and presented more frequently with lymphadenopathy (P = 0·010) and vascular invasion (P = 0·010). Postoperative morbidity and mortality were no different between the groups. The median survival of patients who had surgery after chemotherapy was 24·1 months, and that of patients who had surgery alone was 25·7 months (P = 0·391). CONCLUSION: Patients with locally advanced ICC treated by surgery following neoadjuvant chemotherapy had similar short- and long-term results to patients with initially resectable ICC who had surgery alone. Neoadjuvant chemotherapy as a first-line treatment for locally advanced ICC may be an effective downstaging option, facilitating secondary resectability in patients with initially unresectable disease.","Source":"PubMed","category":"HUMAN","training_data":"Neoadjuvant chemotherapy for initially unresectable intrahepatic cholangiocarcinoma BACKGROUND: Locoregional extension of intrahepatic cholangiocarcinoma (ICC) at the time of diagnosis results in a low resectability rate and poor prognosis. The aim of this retrospective study was to assess the efficacy of neoadjuvant chemotherapy for locally advanced ICC. METHODS: All consecutive patients with ICC between 2000 and 2013 were included prospectively in a single-centre database and analysed retrospectively. Patients with locally advanced ICC considered as initially unresectable received primary chemotherapy, followed by surgery in those with secondary resectability. Results of patients who underwent surgery for locally advanced ICC were compared with those of patients with initially resectable ICC treated by surgery alone. RESULTS: A total of 186 patients were included in the study. Of 74 patients with locally advanced ICC, 39 (53 per cent) underwent secondary resection after a median of six chemotherapy cycles. Patients in this group were younger (P = 0·030) and had more advanced disease than those who had surgery alone, and presented more frequently with lymphadenopathy (P = 0·010) and vascular invasion (P = 0·010). Postoperative morbidity and mortality were no different between the groups. The median survival of patients who had surgery after chemotherapy was 24·1 months, and that of patients who had surgery alone was 25·7 months (P = 0·391). CONCLUSION: Patients with locally advanced ICC treated by surgery following neoadjuvant chemotherapy had similar short- and long-term results to patients with initially resectable ICC who had surgery alone. Neoadjuvant chemotherapy as a first-line treatment for locally advanced ICC may be an effective downstaging option, facilitating secondary resectability in patients with initially unresectable disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"neoadjuvant chemotherapy patients locally advanced gallbladder cancer aim surgery curative option patients gallbladder cancer gbc study looks outcome patients treated neoadjuvant chemotherapy nact patients methods retrospective analysis prospectively maintained database patients locally advanced gbc treated february 2009 september 2013 nact patients received gemcitabine platinum based regimen results total 37 patients median age 54 years 64 9 females received nact overall response rate 67 5 total 17 patients 46 underwent r0 resection median overall survival progression free survival whole group 13 4 8 1 months respectively patients underwent surgery significantly better overall survival median reached vs 9 5 months progression free survival 25 8 vs 5 6 months respectively conclusion nact increases resectability survival patients locally advanced gbc pubmed","probabilities":0.9799733,"Title":"Neoadjuvant chemotherapy in patients with locally advanced gallbladder cancer","Abstract":"AIM: Surgery is the only curative option for patients with gallbladder cancer (GBC). This study looks at the outcome of patients treated with neoadjuvant chemotherapy (NACT). PATIENTS & METHODS: This is retrospective analysis of the prospectively maintained database of patients with locally advanced GBC treated between February 2009 and September 2013 with NACT. Patients received gemcitabine-platinum based regimen. RESULTS: A total of 37 patients (median age: 54 years, 64.9% females) received NACT. Overall response rate was 67.5%. In total, 17 patients (46%) underwent R0 resection. Median overall survival/progression-free survival of the whole group was 13.4/8.1 months, respectively. Patients who underwent surgery had a significantly better overall survival (median not reached vs 9.5 months) and progression-free survival (25.8 vs 5.6 months), respectively. CONCLUSION: NACT increases resectability and survival in patients with locally advanced GBC.","Source":"PubMed","category":"HUMAN","training_data":"Neoadjuvant chemotherapy in patients with locally advanced gallbladder cancer AIM: Surgery is the only curative option for patients with gallbladder cancer (GBC). This study looks at the outcome of patients treated with neoadjuvant chemotherapy (NACT). PATIENTS & METHODS: This is retrospective analysis of the prospectively maintained database of patients with locally advanced GBC treated between February 2009 and September 2013 with NACT. Patients received gemcitabine-platinum based regimen. RESULTS: A total of 37 patients (median age: 54 years, 64.9% females) received NACT. Overall response rate was 67.5%. In total, 17 patients (46%) underwent R0 resection. Median overall survival/progression-free survival of the whole group was 13.4/8.1 months, respectively. Patients who underwent surgery had a significantly better overall survival (median not reached vs 9.5 months) and progression-free survival (25.8 vs 5.6 months), respectively. CONCLUSION: NACT increases resectability and survival in patients with locally advanced GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect preoperative cholangitis prognosis patients hilar cholangiocarcinoma systematic review meta analysis background aim study compare clinical outcomes patients preoperative cholangitis noncholangitis patients determine whether preoperative cholangitis able serve independent predictive factor hilar cholangiocarcinoma hcc outcomes methods systematic literature search reported preoperative cholangitis patients hilar cholangiocarcinoma performed 4 databases pubmed web science embase cochrane library published 1979 2017 results total initial search identified 1228 articles studies 9 studies met inclusion criteria included analysis differences preoperative cholangitis existing noncholangitis patients observed terms mortality rr 2 29 95 ci 1 48 3 52 p 0002 overall morbidity rr 1 15 95 ci 1 00 1 32 p 04 liver failure rr 1 15 95 ci 1 00 1 32 p 04 infection rr 1 52 95 ci 1 16 2 00 p 003 sepsis rr 2 40 95 ci 1 25 4 5 p 008 conclusions results lend support notion hilar cholangiocarcinoma patients existence preoperative cholangitis statistically associated higher postoperative mortality morbidity also increases risk liver failure infection therefore important properly control preoperative cholangitis surgery pubmed","probabilities":0.9799733,"Title":"Effect of preoperative cholangitis on prognosis of patients with hilar cholangiocarcinoma: A systematic review and meta-analysis","Abstract":"BACKGROUND: The aim of this study was to compare the clinical outcomes between patients with preoperative cholangitis and noncholangitis patients to determine whether the preoperative cholangitis would be able to serve as an independent predictive factor on hilar cholangiocarcinoma (HCC) outcomes. METHODS: A systematic literature search for reported preoperative cholangitis in patients with hilar cholangiocarcinoma was performed in 4 databases: PubMed, Web of Science, Embase, and the Cochrane Library, published from 1979 to 2017. RESULTS: In total, the initial search identified 1228 articles. Of these studies only 9 studies met the inclusion criteria and were included in this analysis. Differences between preoperative cholangitis existing and noncholangitis patients were observed in terms of mortality (RR = 2.29; 95% CI = 1.48-3.52; P = .0002), overall morbidity (RR = 1.15;95% CI = 1.00-1.32; P = .04), Liver failure (RR = 1.15;95% CI = 1.00-1.32; P = .04), Infection (RR = 1.52;95% CI = 1.16-2.00; P = .003), sepsis (RR = 2.40;95% CI = 1.25-4.5; P = .008). CONCLUSIONS: The results lend support to the notion that in hilar cholangiocarcinoma patients, the existence of preoperative cholangitis is statistically associated with the higher postoperative mortality and morbidity. Also that it increases the risk of liver failure and infection. therefore, it is very important to properly control the preoperative cholangitis before surgery.","Source":"PubMed","category":"HUMAN","training_data":"Effect of preoperative cholangitis on prognosis of patients with hilar cholangiocarcinoma: A systematic review and meta-analysis BACKGROUND: The aim of this study was to compare the clinical outcomes between patients with preoperative cholangitis and noncholangitis patients to determine whether the preoperative cholangitis would be able to serve as an independent predictive factor on hilar cholangiocarcinoma (HCC) outcomes. METHODS: A systematic literature search for reported preoperative cholangitis in patients with hilar cholangiocarcinoma was performed in 4 databases: PubMed, Web of Science, Embase, and the Cochrane Library, published from 1979 to 2017. RESULTS: In total, the initial search identified 1228 articles. Of these studies only 9 studies met the inclusion criteria and were included in this analysis. Differences between preoperative cholangitis existing and noncholangitis patients were observed in terms of mortality (RR = 2.29; 95% CI = 1.48-3.52; P = .0002), overall morbidity (RR = 1.15;95% CI = 1.00-1.32; P = .04), Liver failure (RR = 1.15;95% CI = 1.00-1.32; P = .04), Infection (RR = 1.52;95% CI = 1.16-2.00; P = .003), sepsis (RR = 2.40;95% CI = 1.25-4.5; P = .008). CONCLUSIONS: The results lend support to the notion that in hilar cholangiocarcinoma patients, the existence of preoperative cholangitis is statistically associated with the higher postoperative mortality and morbidity. Also that it increases the risk of liver failure and infection. therefore, it is very important to properly control the preoperative cholangitis before surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact age race ethnicity women gastrointestinal hepatobiliary malignancies us background incidence rate colorectal cancer crc gallbladder cancer women decreased years incidence rate hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc increased purpose study investigate impact age race ethnicity incidence hcc icc crc gallbladder cancer 2000 2013 women age 20 using surveillance epidemiology end results seer database methods women diagnosed crc hcc icc gallbladder cancers 2000 2013 identified seer registry retrospectively evaluated age specific race ethnicity variations inci dence rates 2000 2006 2007 2013 results total 279 413 women crc 24 267 women hcc 11 132 women gallbladder cancer 4 761 women icc identified women stratified age hcc icc crc gallbladder incidence rates increased age among race ethnic groups incidence rates crc decreased 60 9 50 9 77 3 64 9 50 5 43 3 47 8 42 1 per 100 000 year white black asian hispanic women respectively 2000 2006 2007 2013 black women highest incidence rate incidence rates hcc increased 3 4 4 2 4 7 5 8 7 5 8 5 per 100 000 year white black panic females respectively 2000 2006 2007 2013 asian women highest incidence rate time incidence rates icc increased 0 7 1 0 7 0 8 1 2 1 4 1 1 1 4 per 100 000 year white black hispanic women respectively 2000 2006 2007 2013 asian hispanic women highest inci dence rates incidence rates gallbladder cancer decreased 2 1 9 2 2 2 4 5 4 per 100 000 year white asian hispanic women respectively 2000 2006 2007 2013 incidence rate increased black women 2 3 2 5 per 100 000 year time hispanic women highest incidence rate conclu sion among crc hcc icc gallbladder cancer usa increasing age associated increasing incidence rates incidence gallbladder cancer increased black women years black women highest inci dence rates crc cancer asian women highest incidence rates hcc icc however white women largest percent increase incidence rate years cancers support interventions target specific race ethnic groups women inform importance screening prevention 4 different cancers google scholar","probabilities":0.9799733,"Title":"Impact Of Age And Race/Ethnicity For Women With Gastrointestinal And Hepatobiliary Malignancies In The Us","Abstract":"Background: The incidence rate for colorectal cancer (CRC) and gallbladder cancer for women has decreased over the years while the incidence rate of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have increased. The purpose of this study is investigate the impact of age and race/ethnicity on the incidence of HCC, ICC, CRC, and gallbladder cancer from 2000-2013 for women above the age of 20 using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Women diagnosed with CRC, HCC, ICC and gallbladder cancers from 2000-2013 were identified from the SEER Registry. We retrospectively evaluated age-specific, and race/ethnicity variations in inci-dence rates from 2000-2006 and 2007-2013. Results: A total of 279,413 women with CRC, 24,267 women with HCC, 11,132 women with gallbladder cancer, and 4,761 women with ICC were identified. When women were stratified by age, HCC, ICC, CRC and gallbladder incidence rates increased with age among all race/ethnic groups. The incidence rates for CRC decreased from 60.9 to 50.9, 77.3 to 64.9, 50.5 to 43.3, and 47.8 to 42.1 per 100,000/year for white, black, Asian and Hispanic women respectively from 2000-2006 and 2007-2013. Black women had the highest incidence rate. The incidence rates for HCC increased from 3.4 to 4.2, 4.7 to 5.8, 7.5 to 8.5 per 100,000/year for white, black and His-panic females respectively from 2000-2006 and 2007-2013. Asian women had the highest incidence rate during this time. The incidence rates for ICC increased from 0.7 to 1, 0.7 to 0.8, 1.2 to 1.4, 1.1 to 1.4 per 100,000/year for white, black and Hispanic women respectively from 2000-2006 and 2007-2013. Asian and Hispanic women had the highest inci-dence rates. The incidence rates for gallbladder cancer have decreased from 2 to 1.9, 2.2 to 2, 4.5 to 4 per 100,000/year for white, Asian and Hispanic women respectively from 2000-2006 and 2007 -2013. The incidence rate has increased for black women from 2.3 to 2.5 per 100,000/year during this time. Hispanic women had the highest incidence rate. Conclu-sion: Among CRC, HCC, ICC and gallbladder cancer in the USA, increasing age is associated with increasing incidence rates. Incidence of gallbladder cancer has increased for black women over the years. Black women have the highest inci-dence rates for CRC cancer. Asian women have the highest incidence rates for both HCC and ICC, however, white women have the largest percent increase in incidence rate over the years for these cancers. This would support interventions to target specific race/ethnic groups of women and inform them about the importance of screening and prevention for these 4 different cancers","Source":"Google Scholar","category":"HUMAN","training_data":"Impact Of Age And Race/Ethnicity For Women With Gastrointestinal And Hepatobiliary Malignancies In The Us Background: The incidence rate for colorectal cancer (CRC) and gallbladder cancer for women has decreased over the years while the incidence rate of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) have increased. The purpose of this study is investigate the impact of age and race/ethnicity on the incidence of HCC, ICC, CRC, and gallbladder cancer from 2000-2013 for women above the age of 20 using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: Women diagnosed with CRC, HCC, ICC and gallbladder cancers from 2000-2013 were identified from the SEER Registry. We retrospectively evaluated age-specific, and race/ethnicity variations in inci-dence rates from 2000-2006 and 2007-2013. Results: A total of 279,413 women with CRC, 24,267 women with HCC, 11,132 women with gallbladder cancer, and 4,761 women with ICC were identified. When women were stratified by age, HCC, ICC, CRC and gallbladder incidence rates increased with age among all race/ethnic groups. The incidence rates for CRC decreased from 60.9 to 50.9, 77.3 to 64.9, 50.5 to 43.3, and 47.8 to 42.1 per 100,000/year for white, black, Asian and Hispanic women respectively from 2000-2006 and 2007-2013. Black women had the highest incidence rate. The incidence rates for HCC increased from 3.4 to 4.2, 4.7 to 5.8, 7.5 to 8.5 per 100,000/year for white, black and His-panic females respectively from 2000-2006 and 2007-2013. Asian women had the highest incidence rate during this time. The incidence rates for ICC increased from 0.7 to 1, 0.7 to 0.8, 1.2 to 1.4, 1.1 to 1.4 per 100,000/year for white, black and Hispanic women respectively from 2000-2006 and 2007-2013. Asian and Hispanic women had the highest inci-dence rates. The incidence rates for gallbladder cancer have decreased from 2 to 1.9, 2.2 to 2, 4.5 to 4 per 100,000/year for white, Asian and Hispanic women respectively from 2000-2006 and 2007 -2013. The incidence rate has increased for black women from 2.3 to 2.5 per 100,000/year during this time. Hispanic women had the highest incidence rate. Conclu-sion: Among CRC, HCC, ICC and gallbladder cancer in the USA, increasing age is associated with increasing incidence rates. Incidence of gallbladder cancer has increased for black women over the years. Black women have the highest inci-dence rates for CRC cancer. Asian women have the highest incidence rates for both HCC and ICC, however, white women have the largest percent increase in incidence rate over the years for these cancers. This would support interventions to target specific race/ethnic groups of women and inform them about the importance of screening and prevention for these 4 different cancers Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"hepatocellular carcinoma intrahepatic cholangiocarcinoma us exploring trends since 2001 introduction combined mortality hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc rising worldwide expected uptrend aimed evaluate incidence trends two cancers last 15 years us population methods data extracted national program cancer registries npcr surveillance epidemiology end results seer period 2001 2015 age adjusted incidence annual percent change apc calculated examine trends based type lc gender race seer stat software used analyze data results 334 617 cases types cancers 2001 2015 89 2 hepatocellular carcinoma total 71 4 males 76 caucasians 14 2 african americans 9 8 others significant uptrend incidence rates cancers period 2001 2015 apc 3 6 ci 3 2 4 0 figure 1 rise incidence icc higher hcc apc 7 1 ci 6 1 8 2 3 2 2 6 3 8 respectively table 1 males higher increase hcc apc 3 2 ci 2 6 3 8 females higher risk icc apc 7 6 ci 6 4 88 table 2 caucasians highest apc combined cancers 3 9 3 5 4 3 apcs trending hcc icc among races except race showing apc trending 0 5 ci 1 0 0 1 conclusion data reveal alarming rise incidence rates hcc icc separately combined males females differ rising trends cancers races appear harbor rise cancer incidence identifying treating risk factors crucial prevent fatal disease google scholar","probabilities":0.9799733,"Title":"Hepatocellular Carcinoma And Intrahepatic Cholangiocarcinoma In The Us: Exploring Trends Since 2001","Abstract":"INTRODUCTION:\nThe combined mortality from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is rising worldwide and expected to uptrend. We aimed to evaluate incidence trends of these two cancers over last 15 years in the US population.\nMETHODS:\nData was extracted from National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology and End Results (SEER) for the period 2001-2015. Age-adjusted incidence and annual percent change (APC) were calculated to examine trends based on type of LC, gender, and race. SEER Stat software was used to analyze this data.\nRESULTS:\nThere were 334,617 cases of both types of cancers from 2001 to 2015, of which 89.2% had hepatocellular carcinoma. Total of 71.4% were males, 76% Caucasians, 14.2% African Americans and 9.8% were others. There was significant uptrend in the incidence rates of these cancers for period of 2001-2015 with APC 3.6 (CI: 3.2, 4.0) (Figure 1). The rise in incidence of ICC were higher than HCC with APC of 7.1 (CI: 6.1, 8.2), 3.2 (2.6, 3.8), respectively (Table 1). Males had higher increase in HCC with APC of 3.2 (CI: 2.6, 3.8), and females had higher risk for ICC with APC 7.6 (CI: 6.4, 88.) (Table 2). Caucasians had the highest APC of combined cancers 3.9 (3.5, 4.3). The APCs were trending up for HCC & ICC among all races except in other race, that showing APC was trending down -0.5 (CI: -1.0, -0.1).\nCONCLUSION:\nOur data reveal alarming rise in the incidence rates, for both HCC and ICC, separately and combined. Males and females differ in the rising trends of these cancers and all races appear to harbor rise in the cancer incidence. Identifying and treating risk factors are crucial to prevent this fatal disease.","Source":"Google Scholar","category":"HUMAN","training_data":"Hepatocellular Carcinoma And Intrahepatic Cholangiocarcinoma In The Us: Exploring Trends Since 2001 INTRODUCTION:\nThe combined mortality from hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) is rising worldwide and expected to uptrend. We aimed to evaluate incidence trends of these two cancers over last 15 years in the US population.\nMETHODS:\nData was extracted from National Program of Cancer Registries (NPCR) and Surveillance, Epidemiology and End Results (SEER) for the period 2001-2015. Age-adjusted incidence and annual percent change (APC) were calculated to examine trends based on type of LC, gender, and race. SEER Stat software was used to analyze this data.\nRESULTS:\nThere were 334,617 cases of both types of cancers from 2001 to 2015, of which 89.2% had hepatocellular carcinoma. Total of 71.4% were males, 76% Caucasians, 14.2% African Americans and 9.8% were others. There was significant uptrend in the incidence rates of these cancers for period of 2001-2015 with APC 3.6 (CI: 3.2, 4.0) (Figure 1). The rise in incidence of ICC were higher than HCC with APC of 7.1 (CI: 6.1, 8.2), 3.2 (2.6, 3.8), respectively (Table 1). Males had higher increase in HCC with APC of 3.2 (CI: 2.6, 3.8), and females had higher risk for ICC with APC 7.6 (CI: 6.4, 88.) (Table 2). Caucasians had the highest APC of combined cancers 3.9 (3.5, 4.3). The APCs were trending up for HCC & ICC among all races except in other race, that showing APC was trending down -0.5 (CI: -1.0, -0.1).\nCONCLUSION:\nOur data reveal alarming rise in the incidence rates, for both HCC and ICC, separately and combined. Males and females differ in the rising trends of these cancers and all races appear to harbor rise in the cancer incidence. Identifying and treating risk factors are crucial to prevent this fatal disease. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"e2f1 induced upregulation long non coding rna lmcd1 as1 facilitates cholangiocarcinoma cell progression regulating mir 345 5p col6a3 pathway cholangiocarcinomas cca refractory cancer increasing incidence worldwide long non coding rnas lncrnas shown associate occurrence development cca previous study identified upregulation lmcd1 as1 cca tissues relative normal counterparts agilent human lncrna mrna arrayv4 0 however biological roles molecular mechanisms lmcd1 as1 regulated tumorigenesis progression cca remain elucidated study confirmed lmcd1 as1 expression significantly higher cca tissues cell lines normal tissues hibec respectively e2f1 bind directly promoter region lmcd1 as1 activate transcription function study showed depletion lmcd1 as1 suppressed cell proliferation clone formation invasion induced apoptosis cca cells whereas ectopic expressed lmcd1 as1 facilitated cca cell progression addition lmcd1 as1 sponge mir 345 5p cca cells moreover collagenvi alpha3 chain col6a3 found downstream target mir 345 5p bioinformatic prediction dual luciferase reporter assay furthermore demonstrated oncogenic role lmcd1 as1 partly dependent col6a3 expression taken together reported newly identified regulatory mechanism e2f1 lmcd1 as1 mir 345 5p col6a3 axis might lead better understanding cca tumorigenesis progression provide potential therapeutic targets cca stn","probabilities":0.9467213,"Title":"E2F1-Induced Upregulation Of Long Non-Coding Rna Lmcd1-As1 Facilitates Cholangiocarcinoma Cell Progression By Regulating Mir-345-5P/Col6A3 Pathway","Abstract":"Cholangiocarcinomas (CCA) is a refractory cancer with increasing incidence worldwide. Long non-coding RNAs (lncRNAs) have been shown to associate with the occurrence and development of CCA. A previous study identified upregulation of LMCD1-AS1 in CCA tissues relative to their normal counterparts by Agilent human lncRNA + mRNA arrayV4.0. However, the biological roles and molecular mechanisms of LMCD1-AS1-regulated tumorigenesis and progression of CCA remain to be elucidated. In our study, we confirmed that LMCD1-AS1 expression was significantly higher in CCA tissues and cell lines than in normal tissues and HIBEC, respectively. E2F1 could bind directly to the promoter region of LMCD1-AS1 and activate its transcription. Function study showed depletion of LMCD1-AS1 suppressed cell proliferation, clone formation and invasion, and induced apoptosis of CCA cells. Whereas, ectopic expressed LMCD1-AS1 facilitated CCA cell progression. In addition, LMCD1-AS1 could sponge miR-345-5p in CCA cells. Moreover, collagenVI-alpha3 chain (COL6A3) was found as a downstream target of miR-345-5p by bioinformatic prediction and dual luciferase reporter assay. Furthermore, we demonstrated that the oncogenic role of LMCD1-AS1 is partly dependent on COL6A3 expression. Taken together, we reported a newly identified regulatory mechanism of E2F1/LMCD1-AS1/miR-345-5p/COL6A3 axis, which might lead to a better understanding of CCA tumorigenesis and progression and provide potential therapeutic targets for CCA.","Source":"STN","category":"ANIMAL","training_data":"E2F1-Induced Upregulation Of Long Non-Coding Rna Lmcd1-As1 Facilitates Cholangiocarcinoma Cell Progression By Regulating Mir-345-5P/Col6A3 Pathway Cholangiocarcinomas (CCA) is a refractory cancer with increasing incidence worldwide. Long non-coding RNAs (lncRNAs) have been shown to associate with the occurrence and development of CCA. A previous study identified upregulation of LMCD1-AS1 in CCA tissues relative to their normal counterparts by Agilent human lncRNA + mRNA arrayV4.0. However, the biological roles and molecular mechanisms of LMCD1-AS1-regulated tumorigenesis and progression of CCA remain to be elucidated. In our study, we confirmed that LMCD1-AS1 expression was significantly higher in CCA tissues and cell lines than in normal tissues and HIBEC, respectively. E2F1 could bind directly to the promoter region of LMCD1-AS1 and activate its transcription. Function study showed depletion of LMCD1-AS1 suppressed cell proliferation, clone formation and invasion, and induced apoptosis of CCA cells. Whereas, ectopic expressed LMCD1-AS1 facilitated CCA cell progression. In addition, LMCD1-AS1 could sponge miR-345-5p in CCA cells. Moreover, collagenVI-alpha3 chain (COL6A3) was found as a downstream target of miR-345-5p by bioinformatic prediction and dual luciferase reporter assay. Furthermore, we demonstrated that the oncogenic role of LMCD1-AS1 is partly dependent on COL6A3 expression. Taken together, we reported a newly identified regulatory mechanism of E2F1/LMCD1-AS1/miR-345-5p/COL6A3 axis, which might lead to a better understanding of CCA tumorigenesis and progression and provide potential therapeutic targets for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"photodynamic therapy unresectable cholangiocarcinoma contribution single operator cholangioscopy targeted treatment photodynamic therapy pdt unresectable cholangiocarcinoma associated improvement cholestasis survival single operator cholangioscopy soc used targeted laser illumination analyzed growing experience soc direct pdt retrospective analysis consecutive series patients prospectively entered registry forty five patients 24 male aged 67 3 10 6 years treated pdt cholangiocarcinoma five year period thirty two patients treated ercp pdt alone 13 treated ercp pdt using soc two groups compared observe statistically significant difference regards age gender serum bilirubin meld score adverse effects survival overall median 1 pdt session per patient range 1 9 performed twenty six total sessions pdt using soc performed 13 patients median 2 0 sessions per patient range 1 6 median global survival 168 days range 26 1353 median survival pdt group 200 days median survival pdt soc group 386 days p 0 45 statistically significant difference p 0 0001 two groups regards fluoroscopy time pdt group median time 21 1 min pdt soc group median time 11 1 min pdt related complications included 7 cases mild phototoxicity one case moderate phototoxicity requiring hospitalization soc permits targeted therapy pdt successfully performed without adverse events simultaneously reducing exposure radiation pubmed","probabilities":0.9799733,"Title":"Photodynamic therapy for unresectable cholangiocarcinoma: contribution of single operator cholangioscopy for targeted treatment","Abstract":"Photodynamic therapy (PDT) for unresectable cholangiocarcinoma is associated with improvement in cholestasis and survival. Single operator cholangioscopy (SOC) has been used for targeted laser illumination. We analyzed our growing experience of SOC with direct PDT. This is a retrospective analysis of a consecutive series of patients prospectively entered into a registry. Forty-five patients (24 male, aged 67.3 ± 10.6 years) were treated with PDT for cholangiocarcinoma during a five-year period. Thirty-two patients were treated with ERCP and PDT alone, and 13 were treated with ERCP and PDT using SOC. The two groups were then compared to observe any statistically significant difference in regards to age, gender, serum bilirubin, MELD score, adverse effects, or survival. An overall median of 1 PDT session per patient (range: 1-9) was performed. Twenty-six total sessions of PDT using SOC were performed in 13 patients with a median of 2.0 sessions per patient (range: 1-6). Median global survival was 168 days (range: 26-1353). Median survival for the PDT-only group was 200 days, and median survival for the PDT-with-SOC group was 386 days (p = 0.45). There was a statistically significant difference (p < 0.0001) between the two groups in regards to fluoroscopy time, with the PDT-only group having a median time of 21.1 min and the PDT-with-SOC group having a median time of 11.1 min. PDT related complications included 7 cases of mild phototoxicity and one case of moderate phototoxicity requiring hospitalization. SOC permits targeted therapy during PDT and can be successfully performed without adverse events while simultaneously reducing exposure to radiation.","Source":"PubMed","category":"HUMAN","training_data":"Photodynamic therapy for unresectable cholangiocarcinoma: contribution of single operator cholangioscopy for targeted treatment Photodynamic therapy (PDT) for unresectable cholangiocarcinoma is associated with improvement in cholestasis and survival. Single operator cholangioscopy (SOC) has been used for targeted laser illumination. We analyzed our growing experience of SOC with direct PDT. This is a retrospective analysis of a consecutive series of patients prospectively entered into a registry. Forty-five patients (24 male, aged 67.3 ± 10.6 years) were treated with PDT for cholangiocarcinoma during a five-year period. Thirty-two patients were treated with ERCP and PDT alone, and 13 were treated with ERCP and PDT using SOC. The two groups were then compared to observe any statistically significant difference in regards to age, gender, serum bilirubin, MELD score, adverse effects, or survival. An overall median of 1 PDT session per patient (range: 1-9) was performed. Twenty-six total sessions of PDT using SOC were performed in 13 patients with a median of 2.0 sessions per patient (range: 1-6). Median global survival was 168 days (range: 26-1353). Median survival for the PDT-only group was 200 days, and median survival for the PDT-with-SOC group was 386 days (p = 0.45). There was a statistically significant difference (p < 0.0001) between the two groups in regards to fluoroscopy time, with the PDT-only group having a median time of 21.1 min and the PDT-with-SOC group having a median time of 11.1 min. PDT related complications included 7 cases of mild phototoxicity and one case of moderate phototoxicity requiring hospitalization. SOC permits targeted therapy during PDT and can be successfully performed without adverse events while simultaneously reducing exposure to radiation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ultrasound guided percutaneous microwave ablation versus surgical resection recurrent intrahepatic cholangiocarcinoma intermediate term results objective aims study compare clinical outcomes ultrasound guided percutaneous microwave ablation us pmwa surgical resection sr patients recurrent intrahepatic cholangiocarcinoma icc identify prognostic factors associated two treatment methods methods retrospective study institutional review board approved total 121 patients 102 men 19 women 136 iccs hepatectomy april 2011 january 2017 reviewed fifty six patients underwent us pmwa 65 patients underwent sr survival recurrence liver function compared two groups effect changes key parameters e overall survival os recurrence free survival rfs statistically analyzed log rank test univariate multivariate analysis performed clinicopathological variables identify factors affecting long term outcome results os rfs mwa comparable sr p 405 p 589 respectively estimated 5 year os rates 23 7 mwa 21 8 sr rfs estimated 3 year rfs rates 33 1 mwa 30 6 sr major complication rates sr group higher mwa p 001 sr 13 8 vs mwa 5 3 multivariate analysis showed tumor number p 012 albi grade p 007 metastasis p 016 may become os rate predictors conclusions us pmwa comparable oncologic outcomes sr safe effective treatment recurrent icc hepatectomy pubmed","probabilities":0.9799733,"Title":"Ultrasound-guided percutaneous microwave ablation versus surgical resection for recurrent intrahepatic cholangiocarcinoma: intermediate-term results","Abstract":"OBJECTIVE: The aims of this study were to compare the clinical outcomes between ultrasound-guided percutaneous microwave ablation (US-PMWA) and surgical resection (SR) in patients with recurrent intrahepatic cholangiocarcinoma (ICC) and to identify the prognostic factors associated with the two treatment methods. METHODS: This retrospective study was institutional review board approved. A total of 121 patients (102 men and 19 women) with 136 ICCs after hepatectomy from April 2011 to January 2017 were reviewed. Fifty-six patients underwent US-PMWA and 65 patients underwent SR. Survival, recurrence and liver function were compared between the two groups. Effect of changes in key parameters [i.e., overall survival (OS) and recurrence-free survival (RFS)] was statistically analyzed with the log-rank test. Univariate and multivariate analysis were performed on clinicopathological variables to identify factors affecting long-term outcome. RESULTS: The OS and RFS after MWA were comparable to that of SR (p = .405, and p = .589, respectively). Estimated 5-year OS rates were 23.7% after MWA and 21.8% after SR; for RFS, estimated 3-year RFS rates were 33.1% after MWA and 30.6% after SR. Major complication rates in SR group were higher than that in MWA (p < .001) (SR, 13.8% vs. MWA, 5.3%). Multivariate analysis showed tumor number (p = .012), ALBI grade (p = .007), and metastasis (p = .016), may become OS rate predictors. CONCLUSIONS: US-PMWA had comparable oncologic outcomes with SR and could be a safe and effective treatment for recurrent ICC after hepatectomy.","Source":"PubMed","category":"HUMAN","training_data":"Ultrasound-guided percutaneous microwave ablation versus surgical resection for recurrent intrahepatic cholangiocarcinoma: intermediate-term results OBJECTIVE: The aims of this study were to compare the clinical outcomes between ultrasound-guided percutaneous microwave ablation (US-PMWA) and surgical resection (SR) in patients with recurrent intrahepatic cholangiocarcinoma (ICC) and to identify the prognostic factors associated with the two treatment methods. METHODS: This retrospective study was institutional review board approved. A total of 121 patients (102 men and 19 women) with 136 ICCs after hepatectomy from April 2011 to January 2017 were reviewed. Fifty-six patients underwent US-PMWA and 65 patients underwent SR. Survival, recurrence and liver function were compared between the two groups. Effect of changes in key parameters [i.e., overall survival (OS) and recurrence-free survival (RFS)] was statistically analyzed with the log-rank test. Univariate and multivariate analysis were performed on clinicopathological variables to identify factors affecting long-term outcome. RESULTS: The OS and RFS after MWA were comparable to that of SR (p = .405, and p = .589, respectively). Estimated 5-year OS rates were 23.7% after MWA and 21.8% after SR; for RFS, estimated 3-year RFS rates were 33.1% after MWA and 30.6% after SR. Major complication rates in SR group were higher than that in MWA (p < .001) (SR, 13.8% vs. MWA, 5.3%). Multivariate analysis showed tumor number (p = .012), ALBI grade (p = .007), and metastasis (p = .016), may become OS rate predictors. CONCLUSIONS: US-PMWA had comparable oncologic outcomes with SR and could be a safe and effective treatment for recurrent ICC after hepatectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"downregulation nad p h quinone oxidoreductase 1 inhibits proliferation cell cycle migration cholangiocarcinoma cells previously reported upregulation nad p h quinone oxidoreductase 1 nqo1 cholangiocarcinoma cca fatal bile duct cancer associated poor prognosis also demonstrated suppression nqo1 able enhance chemosensitivity cca cells present study order elucidate biological role nqo1 cca effects small interfering rna sirna mediated knockdown nqo1 cell proliferation cell cycle migration determined kku 100 cca cells notably expressed nqo1 cell proliferation ability cell cycle distribution identified clonogenic cell survival assay flow cytometric analysis respectively wound healing transwell migration assays performed evaluate cell migration molecules involved cell proliferation migration determined western blot analysis reverse transcription quantitative polymerase chain reaction analysis results demonstrated nqo1 sirna mediated knockdown effectively impaired colony formation capacity induced cell cycle arrest g1 phase suppressed migration kku 100 cells cca cells transfected nqo1 sirna exhibited increased expression levels p21 decreased cyclin d1 protein expression levels furthermore ratio matrix metalloproteinase 9 tissue inhibitors metalloproteinases 1 timp1 mrna expression level decreased nqo1 knockdown cells therefore present study provided evidence supporting biological role nqo1 regulation cell proliferation cell cycle migration cca cells therefore nqo1 may prove potential molecular target enhance cca treatment stn","probabilities":0.9467213,"Title":"Downregulation Of Nad(P)H:Quinone Oxidoreductase 1 Inhibits Proliferation Cell Cycle And Migration Of Cholangiocarcinoma Cells","Abstract":"We previously reported that upregulation of NAD(P)H:quinone oxidoreductase 1 (NQO1) in cholangiocarcinoma (CCA; a fatal bile duct cancer) was associated with poor prognosis. It was also demonstrated that the suppression of NQO1 was able to enhance the chemosensitivity of CCA cells. In the present study, in order to elucidate the biological role of NQO1 in CCA, the effects of small interfering RNA (siRNA)-mediated knockdown of NQO1 on cell proliferation, cell cycle and migration were determined in KKU-100 CCA cells, which notably expressed NQO1. The cell proliferation ability and cell cycle distribution were identified by clonogenic cell survival assay and flow cytometric analysis, respectively. Wound healing and Transwell migration assays were performed to evaluate cell migration. The molecules involved in cell proliferation and migration were determined by western blot analysis and reverse transcription-quantitative polymerase chain reaction analysis. The results demonstrated that NQO1 siRNA-mediated knockdown effectively impaired colony formation capacity, induced cell cycle arrest at the G1 phase and suppressed migration of KKU-100 cells. CCA cells transfected with NQO1 siRNA exhibited increased expression levels of p21 and decreased cyclin D1 protein expression levels. Furthermore, the ratio of matrix metalloproteinase 9/tissue inhibitors of metalloproteinases 1 (TIMP1) mRNA expression level was decreased in the NQO1-knockdown cells. Therefore, the present study provided evidence supporting the biological role of NQO1 in the regulation of cell proliferation, cell cycle and migration of CCA cells. Therefore, NQO1 may prove to be a potential molecular target to enhance CCA treatment.","Source":"STN","category":"HUMAN","training_data":"Downregulation Of Nad(P)H:Quinone Oxidoreductase 1 Inhibits Proliferation Cell Cycle And Migration Of Cholangiocarcinoma Cells We previously reported that upregulation of NAD(P)H:quinone oxidoreductase 1 (NQO1) in cholangiocarcinoma (CCA; a fatal bile duct cancer) was associated with poor prognosis. It was also demonstrated that the suppression of NQO1 was able to enhance the chemosensitivity of CCA cells. In the present study, in order to elucidate the biological role of NQO1 in CCA, the effects of small interfering RNA (siRNA)-mediated knockdown of NQO1 on cell proliferation, cell cycle and migration were determined in KKU-100 CCA cells, which notably expressed NQO1. The cell proliferation ability and cell cycle distribution were identified by clonogenic cell survival assay and flow cytometric analysis, respectively. Wound healing and Transwell migration assays were performed to evaluate cell migration. The molecules involved in cell proliferation and migration were determined by western blot analysis and reverse transcription-quantitative polymerase chain reaction analysis. The results demonstrated that NQO1 siRNA-mediated knockdown effectively impaired colony formation capacity, induced cell cycle arrest at the G1 phase and suppressed migration of KKU-100 cells. CCA cells transfected with NQO1 siRNA exhibited increased expression levels of p21 and decreased cyclin D1 protein expression levels. Furthermore, the ratio of matrix metalloproteinase 9/tissue inhibitors of metalloproteinases 1 (TIMP1) mRNA expression level was decreased in the NQO1-knockdown cells. Therefore, the present study provided evidence supporting the biological role of NQO1 in the regulation of cell proliferation, cell cycle and migration of CCA cells. Therefore, NQO1 may prove to be a potential molecular target to enhance CCA treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"thymosin 10 predictive biomarker response 5 fluorouracil chemotherapy cholangiocarcinoma introduction aim 5 fluorouracil 5 fu commonly used chemotherapeutic drug treatment cholangiocarcinoma cca since development drug resistance 5 fu cca patients primary cause treatment failure better understanding mechanism drug resistance cancer essential improve efficacy 5 fu cca therapy material methods 5 fu resistant cca cell line m214 5fur comparative chemo resistance study established real time rt pcr used determine gene expression levels cell cytotoxicity measured mtt assay protein expression levels detected immunofluorescene method results found 5 fu resistance associated overexpression 10 cca cell lines 5 fu treatment various concentrations induced expressions 10 abc transporters abcb1 abcg2 abca3 two cca cell lines kku m055 kku m214 m214 5fur 5 fu resistant cell line exhibited 5 fu resistant phenotype 16 fold extremely high expression 10 abc transporters compared parental cells kku m214 sirna targeted 10 significantly reduced expression abc transporters tested m214 5fur cells p 0 05 conclusions present novel findingsof 10 connected drug resistance shown study provides new insight therapeutic value 10 predictive biomarker 5 fu chemoresistance inhibiting 10 may valuable adjunct suppression abc transporters sensitizing chemotherapy treatment especially 5 fu cca patients stn","probabilities":0.9467213,"Title":"Thymosin ß10 As A Predictive Biomarker Of Response To 5-Fluorouracil Chemotherapy In Cholangiocarcinoma","Abstract":"Introduction and aim. 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic drug in the treatment of cholangiocarcinoma (CCA). Since development of drug resistance to 5-FU in CCA patients is the primary cause of treatment failure, a better understanding of the mechanism of drug resistance of this cancer is essential to improve the efficacy of 5-FU in CCA therapy. \r\n\r\n Material and methods: A 5-FU resistant CCA cell line (M214-5FUR) for a comparative chemo-resistance study was established. Real time RT-PCR was used to determine gene expression levels. Cell cytotoxicity was measured by the MTT assay. Protein expression levels were detected by the immunofluorescene method. \r\n\r\n Results: It was found that 5-FU resistance was associated with the overexpression of T?10 in CCA cell lines. 5-FU treatment at various concentrations induced the expressions of T?10 and ABC transporters (ABCB1, ABCG2 ABCA3) in two CCA cell lines, KKU-M055 and KKU-M214. M214-5FUR, a 5-FU-resistant cell line, exhibited a 5-FU resistant phenotype with a 16-fold extremely high expression of T?10 and ABC transporters, as compared to the parental cells, KKU-M214. siRNA targeted to T?10 significantly reduced expression of ABC transporters tested in the M214-5FUR cells (P < 0.05). \r\n\r\n Conclusions: The present novel findingsof T?10 connected with drug resistance as shown in this study provides a new insight for the therapeutic value of T?10 as a predictive biomarker of 5-FU chemoresistance. Inhibiting T?10 may be a valuable adjunct for suppression of ABC transporters and sensitizing chemotherapy treatment, especially 5-FU in CCA patients.","Source":"STN","category":"ANIMAL","training_data":"Thymosin ß10 As A Predictive Biomarker Of Response To 5-Fluorouracil Chemotherapy In Cholangiocarcinoma Introduction and aim. 5-Fluorouracil (5-FU) is the most commonly used chemotherapeutic drug in the treatment of cholangiocarcinoma (CCA). Since development of drug resistance to 5-FU in CCA patients is the primary cause of treatment failure, a better understanding of the mechanism of drug resistance of this cancer is essential to improve the efficacy of 5-FU in CCA therapy. \r\n\r\n Material and methods: A 5-FU resistant CCA cell line (M214-5FUR) for a comparative chemo-resistance study was established. Real time RT-PCR was used to determine gene expression levels. Cell cytotoxicity was measured by the MTT assay. Protein expression levels were detected by the immunofluorescene method. \r\n\r\n Results: It was found that 5-FU resistance was associated with the overexpression of T?10 in CCA cell lines. 5-FU treatment at various concentrations induced the expressions of T?10 and ABC transporters (ABCB1, ABCG2 ABCA3) in two CCA cell lines, KKU-M055 and KKU-M214. M214-5FUR, a 5-FU-resistant cell line, exhibited a 5-FU resistant phenotype with a 16-fold extremely high expression of T?10 and ABC transporters, as compared to the parental cells, KKU-M214. siRNA targeted to T?10 significantly reduced expression of ABC transporters tested in the M214-5FUR cells (P < 0.05). \r\n\r\n Conclusions: The present novel findingsof T?10 connected with drug resistance as shown in this study provides a new insight for the therapeutic value of T?10 as a predictive biomarker of 5-FU chemoresistance. Inhibiting T?10 may be a valuable adjunct for suppression of ABC transporters and sensitizing chemotherapy treatment, especially 5-FU in CCA patients. STN","prediction_labels":"ANIMAL"},{"cleaned":"impact nodal involvement surgical outcomes intrahepatic cholangiocarcinoma multicenter analysis study group hepatic surgery japanese society hepato biliary pancreatic surgery background purpose aim study clarify prognostic factors intrahepatic cholangiocarcinoma icc following hepatectomy examine impact lymph node metastasis survival study therefore carried project study japanese society hepato biliary pancreatic surgery methods three hundred forty one patients underwent hepatectomy icc 1995 2004 9 institutions medical university hospitals analyzed retrospectively multivariate regression analyses kaplan meyer analysis performed identify prognostic factors results pathological lymph node metastasis one significant factors affecting overall survival hazard ratio 2 10 p 0 001 based multivariate analysis among patients underwent extended lymphadenectomy beyond hepatoduodenal ligament median survival 121 patients nodal involvement 12 2 months seven patients nodal involvement survived 4 years conclusions present study preoperative carbohydrate antigen ca 19 9 intrahepatic metastasis nodal involvement significant independent predictors poor prognosis multivariate analysis prospective studies may thus needed confirm findings study limitation retrospective study multicenter data collection pubmed","probabilities":0.9799733,"Title":"Impact of nodal involvement on surgical outcomes of intrahepatic cholangiocarcinoma: a multicenter analysis by the Study Group for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery","Abstract":"BACKGROUND/PURPOSE: The aim of this study was to clarify the prognostic factors of intrahepatic cholangiocarcinoma (ICC) following hepatectomy and to examine the impact of lymph node metastasis on survival. This study was therefore carried out as a Project Study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. METHODS: Three hundred and forty-one patients who underwent hepatectomy for ICC between 1995 and 2004 at the 9 institutions of the Medical University Hospitals were analyzed retrospectively. Multivariate regression analyses and a Kaplan-Meyer analysis were performed to identify prognostic factors. RESULTS: Pathological lymph node metastasis was one of the significant factors affecting overall survival (hazard ratio 2.10, p < 0.001) based on the multivariate analysis. Among the patients who underwent extended lymphadenectomy beyond the hepatoduodenal ligament, the median survival of 121 patients with nodal involvement was 12.2 months. Only seven patients with nodal involvement have survived for more than 4 years. CONCLUSIONS: In the present study, preoperative carbohydrate antigen (CA) 19-9, intrahepatic metastasis, and nodal involvement were the significant independent predictors of poor prognosis by multivariate analysis. Further prospective studies may thus be needed to confirm these findings, because this study has a limitation in that it was a retrospective study with multicenter data collection.","Source":"PubMed","category":"HUMAN","training_data":"Impact of nodal involvement on surgical outcomes of intrahepatic cholangiocarcinoma: a multicenter analysis by the Study Group for Hepatic Surgery of the Japanese Society of Hepato-Biliary-Pancreatic Surgery BACKGROUND/PURPOSE: The aim of this study was to clarify the prognostic factors of intrahepatic cholangiocarcinoma (ICC) following hepatectomy and to examine the impact of lymph node metastasis on survival. This study was therefore carried out as a Project Study of the Japanese Society of Hepato-Biliary-Pancreatic Surgery. METHODS: Three hundred and forty-one patients who underwent hepatectomy for ICC between 1995 and 2004 at the 9 institutions of the Medical University Hospitals were analyzed retrospectively. Multivariate regression analyses and a Kaplan-Meyer analysis were performed to identify prognostic factors. RESULTS: Pathological lymph node metastasis was one of the significant factors affecting overall survival (hazard ratio 2.10, p < 0.001) based on the multivariate analysis. Among the patients who underwent extended lymphadenectomy beyond the hepatoduodenal ligament, the median survival of 121 patients with nodal involvement was 12.2 months. Only seven patients with nodal involvement have survived for more than 4 years. CONCLUSIONS: In the present study, preoperative carbohydrate antigen (CA) 19-9, intrahepatic metastasis, and nodal involvement were the significant independent predictors of poor prognosis by multivariate analysis. Further prospective studies may thus be needed to confirm these findings, because this study has a limitation in that it was a retrospective study with multicenter data collection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma heterogeneity revealed multigene mutational profiling clinical prognostic relevance surgically resected patients background cholangiocarcinoma classified intrahepatic cholangiocarcinoma icc perihilar cholangiocarcinoma pcc moreover pcc includes two different forms extrahepatic eh pcc arises perihilar eh large ducts intrahepatic ih pcc significant liver mass invades perihilar bile ducts study investigated molecular profile molecular prognostic factors eh pcc ih pcc icc submitted curative surgery methods ninety one patients cholangiocarcinoma 38 eh pcc 18 ih pcc 35 icc underwent curative surgery single tertiary hepatobiliary surgery referral center assessed mutational status 56 cancer related genes results frequently mutated genes eh pcc kras 47 4 tp53 23 7 arid1a 15 8 ih pcc kras 22 2 pbrm1 16 7 pik3ca 16 7 icc idh1 17 1 nras 17 1 bap1 14 3 presence mutations alk idh1 tp53 genes significantly associated poor prognosis patients eh pcc p 0 001 p 0 043 p 0 019 respectively mutation tp53 gene significantly associated poor prognosis patients ih pcc p 0 049 presence mutations arid1a pik3c2g stk11 tgfbr2 tp53 genes significantly associated poor prognosis patients icc p 0 012 p 0 030 p 0 030 p 0 011 p 0 011 respectively conclusions mutational gene profiling identified different gene mutations eh pcc ih pcc icc moreover study reported specific prognostic genes identify patients poor prognosis curative surgery may benefit traditional target adjuvant treatments pubmed","probabilities":0.9799733,"Title":"Cholangiocarcinoma Heterogeneity Revealed by Multigene Mutational Profiling: Clinical and Prognostic Relevance in Surgically Resected Patients","Abstract":"BACKGROUND: Cholangiocarcinoma can be classified in intrahepatic cholangiocarcinoma (ICC) and perihilar cholangiocarcinoma (PCC). Moreover, PCC includes two different forms: extrahepatic (EH) PCC, which arises from the perihilar EH large ducts, and intrahepatic (IH) PCC, in which a significant liver mass invades the perihilar bile ducts. In this study, we investigated the molecular profile and molecular prognostic factors in EH-PCC, IH-PCC, and ICC submitted to curative surgery. METHODS: Ninety-one patients with cholangiocarcinoma (38 EH-PCC, 18 IH-PCC, and 35 ICC), who underwent curative surgery in a single tertiary hepatobiliary surgery referral center were assessed for mutational status in 56 cancer-related genes. RESULTS: The most frequently mutated genes in EH-PCC were KRAS (47.4 %), TP53 (23.7 %) and ARID1A (15.8 %); in IH-PCC were KRAS (22.2 %), PBRM1 (16.7 %), and PIK3CA (16.7 %); and in ICC were IDH1 (17.1 %), NRAS (17.1 %), and BAP1 (14.3 %). The presence of mutations in ALK, IDH1, and TP53 genes was significantly associated with poor prognosis in patients with EH-PCC (p < 0.001, p = 0.043, and p = 0.019, respectively). Mutation of the TP53 gene was significantly associated with poor prognosis in patients with IH-PCC (p = 0.049). The presence of mutations in ARID1A, PIK3C2G, STK11, TGFBR2, and TP53 genes was significantly associated with poor prognosis in patients with ICC (p = 0.012, p = 0.030, p = 0.030, p = 0.011, and p = 0.011, respectively). CONCLUSIONS: Mutational gene profiling identified different gene mutations in EH-PCC, IH-PCC, and ICC. Moreover, our study reported specific prognostic genes that can identify patients with poor prognosis after curative surgery who may benefit from traditional or target adjuvant treatments.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma Heterogeneity Revealed by Multigene Mutational Profiling: Clinical and Prognostic Relevance in Surgically Resected Patients BACKGROUND: Cholangiocarcinoma can be classified in intrahepatic cholangiocarcinoma (ICC) and perihilar cholangiocarcinoma (PCC). Moreover, PCC includes two different forms: extrahepatic (EH) PCC, which arises from the perihilar EH large ducts, and intrahepatic (IH) PCC, in which a significant liver mass invades the perihilar bile ducts. In this study, we investigated the molecular profile and molecular prognostic factors in EH-PCC, IH-PCC, and ICC submitted to curative surgery. METHODS: Ninety-one patients with cholangiocarcinoma (38 EH-PCC, 18 IH-PCC, and 35 ICC), who underwent curative surgery in a single tertiary hepatobiliary surgery referral center were assessed for mutational status in 56 cancer-related genes. RESULTS: The most frequently mutated genes in EH-PCC were KRAS (47.4 %), TP53 (23.7 %) and ARID1A (15.8 %); in IH-PCC were KRAS (22.2 %), PBRM1 (16.7 %), and PIK3CA (16.7 %); and in ICC were IDH1 (17.1 %), NRAS (17.1 %), and BAP1 (14.3 %). The presence of mutations in ALK, IDH1, and TP53 genes was significantly associated with poor prognosis in patients with EH-PCC (p < 0.001, p = 0.043, and p = 0.019, respectively). Mutation of the TP53 gene was significantly associated with poor prognosis in patients with IH-PCC (p = 0.049). The presence of mutations in ARID1A, PIK3C2G, STK11, TGFBR2, and TP53 genes was significantly associated with poor prognosis in patients with ICC (p = 0.012, p = 0.030, p = 0.030, p = 0.011, and p = 0.011, respectively). CONCLUSIONS: Mutational gene profiling identified different gene mutations in EH-PCC, IH-PCC, and ICC. Moreover, our study reported specific prognostic genes that can identify patients with poor prognosis after curative surgery who may benefit from traditional or target adjuvant treatments. PubMed","prediction_labels":"HUMAN"},{"cleaned":"menopausal hormone therapy biliary tract cancer population based matched cohort study sweden background study tested hypothesis contemporary menopausal hormonal therapy mht increases risk biliary tract cancer risk cancer biliary tract gallbladder extra hepatic bile ducts may increased following estrogen exposure material methods nationwide population based matched cohort study sweden data swedish prescribed drug register identified women exposed systemic mht 2005 2012 group level matching 1 3 ratio used select women unexposed mht study base matched history delivery thrombotic events hysterectomy age smoking alcohol related diseases obesity diabetes conditional logistic regression used calculate odds ratios 95 confidence intervals ci results comparing 290 186 women exposed mht 870 165 unexposed mht increase biliary tract cancer gallbladder cancer rather decreased mht users 0 58 95 ci 0 43 0 79 association became attenuated statistically non significant adjusting gallstone disease 0 84 95 ci 0 60 1 15 extra hepatic bile duct cancers 0 83 95 ci 0 61 1 15 clear differences analyses stratified estrogen estrogen progestogen combinations mht increased risk gallstone disease 6 95 95 ci 6 64 7 28 conclusions contemporary mht seem increase risk biliary tract cancer decreased risk gallbladder cancer may explained increased use surgery symptomatic gallstones mht users pubmed","probabilities":0.9799733,"Title":"Menopausal hormone therapy and biliary tract cancer: a population-based matched cohort study in Sweden","Abstract":"BACKGROUND: This study tested the hypothesis that contemporary menopausal hormonal therapy (MHT) increases the risk of biliary tract cancer. The risk of cancer of the biliary tract (gallbladder and extra-hepatic bile ducts) may be increased following estrogen exposure. MATERIAL AND METHODS: This was a nationwide population-based matched cohort study in Sweden. Data from the Swedish Prescribed Drug Register identified all women exposed to systemic MHT in 2005-2012. Group-level matching (1:3 ratio) was used to select women unexposed to MHT from the same study base, matched for history of delivery, thrombotic events, hysterectomy, age, smoking- and alcohol related diseases, obesity, and diabetes. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Comparing 290,186 women exposed to MHT with 870,165 unexposed, MHT did not increase the OR of biliary tract cancer. The OR of gallbladder cancer was rather decreased in MHT users (OR 0.58, 95% CI 0.43-0.79), but this association became attenuated and statistically non-significant after adjusting for gallstone disease (OR 0.84, 95% CI 0.60-1.15). The OR of extra-hepatic bile duct cancers was 0.83 (95% CI 0.61-1.15). There were no clear differences when the analyses were stratified for estrogen or estrogen/progestogen combinations. MHT increased the risk of gallstone disease (OR 6.95, 95% CI 6.64-7.28). CONCLUSIONS: Contemporary MHT does not seem to increase the risk of biliary tract cancer. The decreased risk of gallbladder cancer may be explained by the increased use of surgery for symptomatic gallstones in MHT users.","Source":"PubMed","category":"HUMAN","training_data":"Menopausal hormone therapy and biliary tract cancer: a population-based matched cohort study in Sweden BACKGROUND: This study tested the hypothesis that contemporary menopausal hormonal therapy (MHT) increases the risk of biliary tract cancer. The risk of cancer of the biliary tract (gallbladder and extra-hepatic bile ducts) may be increased following estrogen exposure. MATERIAL AND METHODS: This was a nationwide population-based matched cohort study in Sweden. Data from the Swedish Prescribed Drug Register identified all women exposed to systemic MHT in 2005-2012. Group-level matching (1:3 ratio) was used to select women unexposed to MHT from the same study base, matched for history of delivery, thrombotic events, hysterectomy, age, smoking- and alcohol related diseases, obesity, and diabetes. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Comparing 290,186 women exposed to MHT with 870,165 unexposed, MHT did not increase the OR of biliary tract cancer. The OR of gallbladder cancer was rather decreased in MHT users (OR 0.58, 95% CI 0.43-0.79), but this association became attenuated and statistically non-significant after adjusting for gallstone disease (OR 0.84, 95% CI 0.60-1.15). The OR of extra-hepatic bile duct cancers was 0.83 (95% CI 0.61-1.15). There were no clear differences when the analyses were stratified for estrogen or estrogen/progestogen combinations. MHT increased the risk of gallstone disease (OR 6.95, 95% CI 6.64-7.28). CONCLUSIONS: Contemporary MHT does not seem to increase the risk of biliary tract cancer. The decreased risk of gallbladder cancer may be explained by the increased use of surgery for symptomatic gallstones in MHT users. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological operative factors prognosis carcinoma ampulla vater background aims prognostic factor carcinoma ampulla vater analyzed retrospectively significance lymphadenectomy around superior mesenteric artery para aortic region clinical outcome evaluated methodology 1985 2008 34 carcinomas ampulla vater patients underwent pancreaticoduodenectomy curative intent analyzed respect tumor extent operation method prognosis results overall 5 year survival 52 6 multivariate analysis lymph node metastasis pancreatic invasion venous invasion perineural invasion lymphadenectomy around superior mesenteric artery significant prognostic factors however dissection para aortic lymph nodes substantial survival benefit compared duodenal cancer prognosis carcinoma ampulla vater significantly worse although differences clinicopathological characteristics patients observed conclusions lymph node metastasis pancreatic invasion venous invasion perineural invasion lymphadenectomy around superior mesenteric artery important prognostic factors pylorus preserving pancreaticoduodenectomy lymphadenectomy around superior mesenteric artery without dissection para aortic lymph nodes recommended optimal surgery though treatment results worse duodenal cancer curative operation performed regardless site origin pubmed","probabilities":0.9799733,"Title":"Clinicopathological and operative factors for prognosis of carcinoma of the ampulla of vater","Abstract":"BACKGROUND/AIMS: The prognostic factor(s) of carcinoma of the ampulla of Vater were analyzed retrospectively and the significance of lymphadenectomy around the superior mesenteric artery and para-aortic region on the clinical outcome was evaluated. METHODOLOGY: From 1985 to 2008, 34 carcinomas of the ampulla of Vater patients who underwent pancreaticoduodenectomy with curative intent were analyzed with respect to tumor extent, operation method and prognosis. RESULTS: Overall 5-year survival was 52.6%. On multivariate analysis, lymph node metastasis, pancreatic invasion, venous invasion, perineural invasion and lymphadenectomy around the superior mesenteric artery were the significant prognostic factors. However, the dissection of para-aortic lymph nodes had no substantial survival benefit. Compared with the duodenal cancer, the prognosis for carcinoma of the ampulla of Vater was significantly worse although no differences in clinicopathological characteristics of patients were observed. CONCLUSIONS: Lymph node metastasis, pancreatic invasion, venous invasion, perineural invasion, and lymphadenectomy around the superior mesenteric artery are important prognostic factors. Pylorus-preserving pancreaticoduodenectomy, with lymphadenectomy around the superior mesenteric artery without dissection of para-aortic lymph nodes is recommended as optimal surgery. Though the treatment results were worse than that of duodenal cancer, curative operation should be performed, regardless of site of origin.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological and operative factors for prognosis of carcinoma of the ampulla of vater BACKGROUND/AIMS: The prognostic factor(s) of carcinoma of the ampulla of Vater were analyzed retrospectively and the significance of lymphadenectomy around the superior mesenteric artery and para-aortic region on the clinical outcome was evaluated. METHODOLOGY: From 1985 to 2008, 34 carcinomas of the ampulla of Vater patients who underwent pancreaticoduodenectomy with curative intent were analyzed with respect to tumor extent, operation method and prognosis. RESULTS: Overall 5-year survival was 52.6%. On multivariate analysis, lymph node metastasis, pancreatic invasion, venous invasion, perineural invasion and lymphadenectomy around the superior mesenteric artery were the significant prognostic factors. However, the dissection of para-aortic lymph nodes had no substantial survival benefit. Compared with the duodenal cancer, the prognosis for carcinoma of the ampulla of Vater was significantly worse although no differences in clinicopathological characteristics of patients were observed. CONCLUSIONS: Lymph node metastasis, pancreatic invasion, venous invasion, perineural invasion, and lymphadenectomy around the superior mesenteric artery are important prognostic factors. Pylorus-preserving pancreaticoduodenectomy, with lymphadenectomy around the superior mesenteric artery without dissection of para-aortic lymph nodes is recommended as optimal surgery. Though the treatment results were worse than that of duodenal cancer, curative operation should be performed, regardless of site of origin. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association helicobacter spp infections hepatobiliary malignancies review hepatobiliary cancers highly lethal cancers comprise spectrum invasive carcinomas originating liver hepatocellular carcinoma bile ducts intrahepatic cholangiocarcinoma extrahepatic cholangiocarcinoma gallbladder ampulla vater collectively known biliary tract cancers tumors account approximately 13 annual cancer related deaths worldwide 10 20 deaths hepatobiliary malignancies cholangiocarcinoma cca devastating disease displays poor survival rate therapeutic options available population genetics geographical environmental factors cholelithiasis obesity parity endemic infection liver flukes identified risk factors influence development biliary tract tumors important factors affecting carcinogenesis tumors include chronic inflammation obstruction bile ducts impaired bile flow suggested cca caused infection helicobacter species helicobacter bilis helicobacter hepaticus manner similar reported role helicobacter pylori distal gastric cancer due difficulty culturing helicobacter species molecular methods polymerase chain reaction sequencing immunologic assays become methods choice diagnosis however clinical studies benign malignant biliary tract diseases revealed remarkable variability methods findings use uniform validated techniques needed pubmed","probabilities":0.5555556,"Title":"Association between Helicobacter spp infections and hepatobiliary malignancies: a review","Abstract":"Hepatobiliary cancers are highly lethal cancers that comprise a spectrum of invasive carcinomas originating in the liver hepatocellular carcinoma, the bile ducts intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, the gallbladder and the ampulla of Vater (collectively known as biliary tract cancers). These tumors account for approximately 13% of all annual cancer-related deaths worldwide and for 10%-20% of deaths from hepatobiliary malignancies. Cholangiocarcinoma (CCA) is a devastating disease that displays a poor survival rate for which few therapeutic options are available. Population genetics, geographical and environmental factors, cholelithiasis, obesity, parity, and endemic infection with liver flukes have been identified as risk factors that influence the development of biliary tract tumors. Other important factors affecting the carcinogenesis of these tumors include chronic inflammation, obstruction of the bile ducts, and impaired bile flow. It has been suggested that CCA is caused by infection with Helicobacter species, such as Helicobacter bilis and Helicobacter hepaticus, in a manner that is similar to the reported role of Helicobacter pylori in distal gastric cancer. Due to the difficulty in culturing these Helicobacter species, molecular methods, such as polymerase chain reaction and sequencing, or immunologic assays have become the methods of choice for diagnosis. However, clinical studies of benign or malignant biliary tract diseases revealed remarkable variability in the methods and the findings, and the use of uniform and validated techniques is needed.","Source":"PubMed","category":"HUMAN","training_data":"Association between Helicobacter spp infections and hepatobiliary malignancies: a review Hepatobiliary cancers are highly lethal cancers that comprise a spectrum of invasive carcinomas originating in the liver hepatocellular carcinoma, the bile ducts intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, the gallbladder and the ampulla of Vater (collectively known as biliary tract cancers). These tumors account for approximately 13% of all annual cancer-related deaths worldwide and for 10%-20% of deaths from hepatobiliary malignancies. Cholangiocarcinoma (CCA) is a devastating disease that displays a poor survival rate for which few therapeutic options are available. Population genetics, geographical and environmental factors, cholelithiasis, obesity, parity, and endemic infection with liver flukes have been identified as risk factors that influence the development of biliary tract tumors. Other important factors affecting the carcinogenesis of these tumors include chronic inflammation, obstruction of the bile ducts, and impaired bile flow. It has been suggested that CCA is caused by infection with Helicobacter species, such as Helicobacter bilis and Helicobacter hepaticus, in a manner that is similar to the reported role of Helicobacter pylori in distal gastric cancer. Due to the difficulty in culturing these Helicobacter species, molecular methods, such as polymerase chain reaction and sequencing, or immunologic assays have become the methods of choice for diagnosis. However, clinical studies of benign or malignant biliary tract diseases revealed remarkable variability in the methods and the findings, and the use of uniform and validated techniques is needed. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"epidemiology intrahepatic perihilar distal cholangiocarcinoma french population objectives objective study investigate differences cholangiocarcinoma cc subtypes terms incidence rate clinical presentation management survival applying stable anatomical classification population based study patients methods cancer data period 2000 2012 obtained specialized digestive cancer registry department calvados france patients files checked diagnosis verified two hepatobiliary surgeons approach prevents classifying perihilar cholangiocarcinoma phcc intrahepatic cholangiocarcinoma icc thereby allowing accurate estimation respective epidemiological characteristics results total 320 patients cc included icc represented 41 130 whereas phcc distal cholangiocarcinoma represented 36 116 23 74 respectively mean age time diagnosis differed significantly three subtypes p 0 05 icc discovered accidently frequently phcc associated significantly clinical symptoms change incidence survival rates cc subtypes noticed except phcc female individuals significantly shorter median 5 year survival rate 0 p 0 05 conclusion frequency phcc overestimated literature anatomical reclassification cc subtypes shows stability incidence survival rates considering icc phcc two different entities implies need assign specific topographic code phcc stn","probabilities":0.9799733,"Title":"Epidemiology Of Intrahepatic Perihilar And Distal Cholangiocarcinoma In The French Population","Abstract":"Objectives: The objective of this study was to investigate the differences between cholangiocarcinoma (CC) subtypes in terms of incidence rate, clinical presentation, management and survival by applying a stable anatomical classification in a population-based study. \r\n\r\n Patients and methods: Cancer data for the period 2000-2012 were obtained from a specialized digestive cancer registry in the Department of Calvados, France. Patients' files were checked, and the diagnosis was verified by two hepatobiliary surgeons. This approach prevents classifying perihilar cholangiocarcinoma (PHCC) as intrahepatic cholangiocarcinoma (ICC), thereby allowing an accurate estimation of their respective epidemiological characteristics. \r\n\r\n Results: A total of 320 patients with CC were included. ICC represented 41% (130), whereas PHCC and distal cholangiocarcinoma represented 36 (116) and 23% (74), respectively. The mean age at the time of diagnosis differed significantly between the three subtypes (P<0.05). ICC was discovered accidently more frequently than PHCC, which was associated significantly with clinical symptoms. No change in the incidence or survival rates of CC subtypes were noticed, except for PHCC, in which female individuals had a significantly shorter median and 5-year survival rate of 0% (P<0.05). \r\n\r\n Conclusion: The frequency of PHCC is overestimated in the literature. The anatomical reclassification of CC subtypes shows the stability of their incidence and survival rates. Considering ICC and PHCC as two different entities implies the need to assign a specific topographic code for PHCC.","Source":"STN","category":"HUMAN","training_data":"Epidemiology Of Intrahepatic Perihilar And Distal Cholangiocarcinoma In The French Population Objectives: The objective of this study was to investigate the differences between cholangiocarcinoma (CC) subtypes in terms of incidence rate, clinical presentation, management and survival by applying a stable anatomical classification in a population-based study. \r\n\r\n Patients and methods: Cancer data for the period 2000-2012 were obtained from a specialized digestive cancer registry in the Department of Calvados, France. Patients' files were checked, and the diagnosis was verified by two hepatobiliary surgeons. This approach prevents classifying perihilar cholangiocarcinoma (PHCC) as intrahepatic cholangiocarcinoma (ICC), thereby allowing an accurate estimation of their respective epidemiological characteristics. \r\n\r\n Results: A total of 320 patients with CC were included. ICC represented 41% (130), whereas PHCC and distal cholangiocarcinoma represented 36 (116) and 23% (74), respectively. The mean age at the time of diagnosis differed significantly between the three subtypes (P<0.05). ICC was discovered accidently more frequently than PHCC, which was associated significantly with clinical symptoms. No change in the incidence or survival rates of CC subtypes were noticed, except for PHCC, in which female individuals had a significantly shorter median and 5-year survival rate of 0% (P<0.05). \r\n\r\n Conclusion: The frequency of PHCC is overestimated in the literature. The anatomical reclassification of CC subtypes shows the stability of their incidence and survival rates. Considering ICC and PHCC as two different entities implies the need to assign a specific topographic code for PHCC. STN","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma analysis 44 consecutive resected cases including 5 cases repeat resections background prognosis resection intrahepatic cholangiocarcinoma icc remains unsatisfactory remains effective therapy recurrent icc objective current study sought evaluate risk factors associated recurrent icc possible therapies resection method review data patients underwent potentially curative resection icc performed results total 44 potentially curative resections performed 1995 2008 mortality 0 morbidity 35 5 year overall recurrence free survival rates 43 39 respectively multivariate analysis identified presence multiple nodules poor histologic grade independent negative prognostic factors overall recurrent free survival postoperative recurrence occurred 25 patients 57 solitary recurrence occurred 5 patients liver n 4 lung n 1 undergone surgical resection three 5 patients survived 5 years 2 resections conclusion prognosis curative resection solitary icc appears favorable selected patients sequential single hepatic pulmonary recurrence repeat resection may prolong survival pubmed","probabilities":0.9799733,"Title":"Intrahepatic cholangiocarcinoma: analysis of 44 consecutive resected cases including 5 cases with repeat resections","Abstract":"BACKGROUND: Prognosis after resection for intrahepatic cholangiocarcinoma (ICC) remains unsatisfactory. There remains no effective therapy after recurrent ICC. OBJECTIVE: The current study sought to evaluate risk factors associated with recurrent ICC and possible therapies after resection. METHOD: A review of data from patients who underwent potentially curative resection for ICC was performed. RESULTS: A total of 44 potentially curative resections were performed from 1995 to 2008. Mortality was 0% and morbidity was 35%. The 5-year overall and recurrence-free survival rates were 43% and 39%, respectively. Multivariate analysis identified the presence of multiple nodules and poor histologic grade as independent negative prognostic factors for overall and recurrent-free survival. Postoperative recurrence occurred in 25 patients (57%). Solitary recurrence occurred in 5 patients (liver, n = 4; lung, n = 1), all of who had undergone surgical resection. Three of the 5 patients survived for more than 5 years after 2 resections. CONCLUSION: Prognosis after curative resection of solitary ICC appears favorable. In selected patients with sequential single hepatic or pulmonary recurrence, repeat resection may prolong survival.","Source":"PubMed","category":"HUMAN","training_data":"Intrahepatic cholangiocarcinoma: analysis of 44 consecutive resected cases including 5 cases with repeat resections BACKGROUND: Prognosis after resection for intrahepatic cholangiocarcinoma (ICC) remains unsatisfactory. There remains no effective therapy after recurrent ICC. OBJECTIVE: The current study sought to evaluate risk factors associated with recurrent ICC and possible therapies after resection. METHOD: A review of data from patients who underwent potentially curative resection for ICC was performed. RESULTS: A total of 44 potentially curative resections were performed from 1995 to 2008. Mortality was 0% and morbidity was 35%. The 5-year overall and recurrence-free survival rates were 43% and 39%, respectively. Multivariate analysis identified the presence of multiple nodules and poor histologic grade as independent negative prognostic factors for overall and recurrent-free survival. Postoperative recurrence occurred in 25 patients (57%). Solitary recurrence occurred in 5 patients (liver, n = 4; lung, n = 1), all of who had undergone surgical resection. Three of the 5 patients survived for more than 5 years after 2 resections. CONCLUSION: Prognosis after curative resection of solitary ICC appears favorable. In selected patients with sequential single hepatic or pulmonary recurrence, repeat resection may prolong survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"helicobacter species infection may associated cholangiocarcinoma meta analysis objective since discovery helicobacter species human biliary system association helicobacter species infection cholangiocarcinoma debate meta analysis aims explore issue methods literature search carried identify eligible articles performed overall meta analysis included studies subgroup analysis based regional distribution subgroup analysis light detection methods specimens also conducted results ten case control studies included overall meta analysis favoured significant association helicobacter species infection cholangiocarcinoma cumulative 8 88 95 ci 3 67 21 49 subgroup analysis based geographic distribution indicated helicobacter species infection may serve risk factor region high cholangiocarcinoma incidence asia 6 68 95 ci 2 29 19 49 also low incidence region europe 14 90 95 ci 4 79 46 35 subgroup analysis showed pcr effective efficient method detect helicobacter species surgically resected tissue bile significant heterogeneity among studies obvious publication bias conclusion meta analysis supports possible association helicobacter species infection cholangiocarcinoma investigations required clarify role helicobacter species malignancy pubmed","probabilities":0.8684211,"Title":"Helicobacter species infection may be associated with cholangiocarcinoma: a meta-analysis","Abstract":"OBJECTIVE: Since the discovery of Helicobacter species in human biliary system, the association between Helicobacter species infection and cholangiocarcinoma is under debate. This meta-analysis aims to explore this issue. METHODS: Literature search was carried out to identify all eligible articles. We performed overall meta-analysis of all included studies and subgroup analysis based on regional distribution. Subgroup analysis in the light of detection methods and specimens was also conducted. RESULTS: Ten case-control studies were included. Overall meta-analysis favoured a significant association between Helicobacter species infection and cholangiocarcinoma (cumulative OR 8.88, 95% CI 3.67-21.49). Subgroup analysis based on geographic distribution indicated that Helicobacter species infection may serve as a risk factor not only in a region with high cholangiocarcinoma incidence (Asia, OR 6.68, 95% CI 2.29-19.49) but also in low incidence region (Europe, OR 14.90, 95% CI 4.79-46.35). The other subgroup analysis showed that PCR was the most effective and efficient method to detect Helicobacter species in surgically resected tissue and bile. There was significant heterogeneity among studies and obvious publication bias. CONCLUSION: Our meta-analysis supports the possible association between Helicobacter species infection and cholangiocarcinoma. Further investigations are required to clarify the role of Helicobacter species in this malignancy.","Source":"PubMed","category":"HUMAN","training_data":"Helicobacter species infection may be associated with cholangiocarcinoma: a meta-analysis OBJECTIVE: Since the discovery of Helicobacter species in human biliary system, the association between Helicobacter species infection and cholangiocarcinoma is under debate. This meta-analysis aims to explore this issue. METHODS: Literature search was carried out to identify all eligible articles. We performed overall meta-analysis of all included studies and subgroup analysis based on regional distribution. Subgroup analysis in the light of detection methods and specimens was also conducted. RESULTS: Ten case-control studies were included. Overall meta-analysis favoured a significant association between Helicobacter species infection and cholangiocarcinoma (cumulative OR 8.88, 95% CI 3.67-21.49). Subgroup analysis based on geographic distribution indicated that Helicobacter species infection may serve as a risk factor not only in a region with high cholangiocarcinoma incidence (Asia, OR 6.68, 95% CI 2.29-19.49) but also in low incidence region (Europe, OR 14.90, 95% CI 4.79-46.35). The other subgroup analysis showed that PCR was the most effective and efficient method to detect Helicobacter species in surgically resected tissue and bile. There was significant heterogeneity among studies and obvious publication bias. CONCLUSION: Our meta-analysis supports the possible association between Helicobacter species infection and cholangiocarcinoma. Further investigations are required to clarify the role of Helicobacter species in this malignancy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"neutrophil lymphocyte ratio prognostic factor biliary tract cancer background biliary tract cancers btcs include intrahepatic ihc hilar distal bile duct dbd gallbladder carcinoma gbc neutrophil lymphocyte ratio nlr marker host inflammation prognostic several cancers reviewed large btc series advanced btc abtc diagnosis patients methods baseline demographics nlr diagnosis retrospectively evaluated 864 consecutive patients btc treated january 1987 december 2012 association nlr overall survival os determined using multivariable cox proportional hazards model results eight hundred sixty four patients included analysis 62 abtc 38 surgery curative intent median age 65 years 444 51 male 727 84 performance status ps 2 nlr 3 0 ps 2 ihc primary stage lack surgery haemoglobin 110 g l albumin 40 g l associated significantly worse os multivariable analysis nlr 3 0 independent prognostic factor os entire cohort median os 21 6 months versus 12 0 months patients nlr 3 0 versus nlr 3 0 respectively adjusted hazard ratio hr 1 26 95 confidence interval ci 1 06 1 50 p 0 01 nlr also prognostic patients abtc hr 1 26 95 ci 1 02 1 56 p 0 035 hilar cancer overall group n 149 hr 1 70 95 ci 1 10 2 50 p 0 01 advanced group n 111 hr 1 57 95 ci 1 04 2 44 p 0 048 conclusion baseline nlr readily available inexpensive prognostic biomarker patients btc likely warrants validation large prospective clinical trials pubmed","probabilities":0.9799733,"Title":"Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer","Abstract":"BACKGROUND: Biliary tract cancers (BTCs) include intrahepatic (IHC), hilar, distal bile duct (DBD) and gallbladder carcinoma (GBC). Neutrophil/lymphocyte ratio (NLR), a marker of host inflammation, is prognostic in several cancers but has not been reviewed in large BTC series, or advanced BTC (ABTC) at diagnosis. PATIENTS AND METHODS: Baseline demographics and NLR at diagnosis were retrospectively evaluated in 864 consecutive patients with BTC treated from January 1987 to December 2012. The association between NLR and overall survival (OS) was determined using a multivariable Cox proportional hazards model. RESULTS: Eight hundred and sixty-four patients were included in the analysis, of which 62% had ABTC and 38% had surgery with curative intent. Median age was 65 years, 444 (51%) were male and 727 (84%) had performance status (PS) ⩽ 2. A NLR ⩾ 3.0, PS >2, IHC primary, stage, lack of surgery, haemoglobin <110 g/L and albumin <40 g/L were associated with significantly worse OS on multivariable analysis. A NLR ⩾ 3.0 was an independent prognostic factor for OS for the entire cohort; median OS was 21.6 months versus 12.0 months for patients with NLR <3.0 versus NLR ⩾ 3.0 respectively (adjusted hazard ratio (HR)-1.26, 95% confidence interval (CI); 1.06-1.50, P = 0.01). NLR was also prognostic in patients with ABTC (HR-1.26, 95% CI; 1.02-1.56, P = 0.035) and hilar cancer: overall group (N = 149) (HR-1.70, 95% CI; 1.10-2.50, P = 0.01) and advanced group (N = 111) (HR-1.57, 95% CI; 1.04-2.44, P = 0.048). CONCLUSION: Baseline NLR is a readily available and inexpensive prognostic biomarker in patients with BTC and likely warrants validation in large prospective clinical trials.","Source":"PubMed","category":"HUMAN","training_data":"Neutrophil/lymphocyte ratio as a prognostic factor in biliary tract cancer BACKGROUND: Biliary tract cancers (BTCs) include intrahepatic (IHC), hilar, distal bile duct (DBD) and gallbladder carcinoma (GBC). Neutrophil/lymphocyte ratio (NLR), a marker of host inflammation, is prognostic in several cancers but has not been reviewed in large BTC series, or advanced BTC (ABTC) at diagnosis. PATIENTS AND METHODS: Baseline demographics and NLR at diagnosis were retrospectively evaluated in 864 consecutive patients with BTC treated from January 1987 to December 2012. The association between NLR and overall survival (OS) was determined using a multivariable Cox proportional hazards model. RESULTS: Eight hundred and sixty-four patients were included in the analysis, of which 62% had ABTC and 38% had surgery with curative intent. Median age was 65 years, 444 (51%) were male and 727 (84%) had performance status (PS) ⩽ 2. A NLR ⩾ 3.0, PS >2, IHC primary, stage, lack of surgery, haemoglobin <110 g/L and albumin <40 g/L were associated with significantly worse OS on multivariable analysis. A NLR ⩾ 3.0 was an independent prognostic factor for OS for the entire cohort; median OS was 21.6 months versus 12.0 months for patients with NLR <3.0 versus NLR ⩾ 3.0 respectively (adjusted hazard ratio (HR)-1.26, 95% confidence interval (CI); 1.06-1.50, P = 0.01). NLR was also prognostic in patients with ABTC (HR-1.26, 95% CI; 1.02-1.56, P = 0.035) and hilar cancer: overall group (N = 149) (HR-1.70, 95% CI; 1.10-2.50, P = 0.01) and advanced group (N = 111) (HR-1.57, 95% CI; 1.04-2.44, P = 0.048). CONCLUSION: Baseline NLR is a readily available and inexpensive prognostic biomarker in patients with BTC and likely warrants validation in large prospective clinical trials. PubMed","prediction_labels":"HUMAN"},{"cleaned":"efficacy safety sorafenib unresectable hepatocellular carcinoma bile duct invasion introduction frequency bile duct invasion hepatocellular carcinoma hcc patients rare limited clinical evidence demonstrate outcomes systemic therapy hcc bile duct invasion objective aim clarify efficacy safety sorafenib treatment patients unresectable advanced hcc bile duct invasion methods one hundred seventy five patients advanced hcc enrolled study retrospectively compared outcomes sorafenib patients without bile duct invasion b group n 165 bile duct invasion b group n 10 results significant differences confirmed objective response rate orr confirmed disease control dc rate b b groups 13 9 vs 20 0 p 0 637 orr 47 2 vs 70 0 p 0 202 dc rate respectively significant differences median overall survival os time progression ttp b group b group 14 8 vs 14 1 months p 0 780 os 3 4 vs 5 7 months p 0 277 ttp respectively post treatment factors associated good os changes albumin bilirubin score 0 6 weeks 0 25 antitumor response 6 weeks dc though 5 10 patients 50 b group bile duct complications obstructive jaundice biliary bleeding 5 patients able recover biliary troubles careful vigorous management biliary endoscopic intervention able continue sorafenib therapy safely conclusions present results suggest sorafenib might potential therapeutic efficacy safety advanced hcc patients bile duct invasion case biliary tract troubles sorafenib treatment early biliary management may important continue sorafenib therapy safely studies needed confirm outcomes sorafenib advanced hcc patients bile duct invasion stn","probabilities":0.9799733,"Title":"Efficacy And Safety Of Sorafenib In Unresectable Hepatocellular Carcinoma With Bile Duct Invasion","Abstract":"Introduction: Because the frequency of bile duct invasion in hepatocellular carcinoma (HCC) patients is very rare, there is limited clinical evidence to demonstrate the outcomes of systemic therapy in HCC with bile duct invasion. \r\n\r\n Objective: Our aim was to clarify the efficacy and safety of sorafenib treatment in patients with unresectable advanced HCC with bile duct invasion. \r\n\r\n Methods: One hundred and seventy-five patients with advanced HCC were enrolled in this study. We retrospectively compared the outcomes of sorafenib between patients without bile duct invasion [B (-) group, n = 165] and those with bile duct invasion [B (+) group, n = 10]. \r\n\r\n Results: There were no significant differences in the confirmed objective response rate (ORR) and the confirmed disease control (DC) rate between the B (-) and the B (+) groups (13.9 vs. 20.0%, p = 0.637 for ORR; 47.2 vs. 70.0%, p = 0.202 for DC rate, respectively). There were no significant differences in median overall survival (OS) and time to progression (TTP) between the B (-) group and the B (+) group (14.8 vs. 14.1 months, p = 0.780 for OS; 3.4 vs. 5.7 months, p = 0.277 for TTP, respectively). Post-treatment factors associated with good OS were changes in albumin-bilirubin score (0-6 weeks) of <0.25, and antitumor response at 6 weeks of DC. Though 5 of 10 patients (50%) in the B (+) group had bile duct complications, such as obstructive jaundice and biliary bleeding, these 5 patients were able to recover from biliary troubles by careful and vigorous management with biliary endoscopic intervention, and were able to continue sorafenib therapy safely. \r\n\r\n Conclusions: Our present results suggest that sorafenib might have potential therapeutic efficacy and safety in advanced HCC patients with bile duct invasion. In case of biliary tract troubles before and during sorafenib treatment, early biliary management may be important to continue sorafenib therapy safely. Further studies are needed to confirm the outcomes of sorafenib in advanced HCC patients with bile duct invasion.","Source":"STN","category":"HUMAN","training_data":"Efficacy And Safety Of Sorafenib In Unresectable Hepatocellular Carcinoma With Bile Duct Invasion Introduction: Because the frequency of bile duct invasion in hepatocellular carcinoma (HCC) patients is very rare, there is limited clinical evidence to demonstrate the outcomes of systemic therapy in HCC with bile duct invasion. \r\n\r\n Objective: Our aim was to clarify the efficacy and safety of sorafenib treatment in patients with unresectable advanced HCC with bile duct invasion. \r\n\r\n Methods: One hundred and seventy-five patients with advanced HCC were enrolled in this study. We retrospectively compared the outcomes of sorafenib between patients without bile duct invasion [B (-) group, n = 165] and those with bile duct invasion [B (+) group, n = 10]. \r\n\r\n Results: There were no significant differences in the confirmed objective response rate (ORR) and the confirmed disease control (DC) rate between the B (-) and the B (+) groups (13.9 vs. 20.0%, p = 0.637 for ORR; 47.2 vs. 70.0%, p = 0.202 for DC rate, respectively). There were no significant differences in median overall survival (OS) and time to progression (TTP) between the B (-) group and the B (+) group (14.8 vs. 14.1 months, p = 0.780 for OS; 3.4 vs. 5.7 months, p = 0.277 for TTP, respectively). Post-treatment factors associated with good OS were changes in albumin-bilirubin score (0-6 weeks) of <0.25, and antitumor response at 6 weeks of DC. Though 5 of 10 patients (50%) in the B (+) group had bile duct complications, such as obstructive jaundice and biliary bleeding, these 5 patients were able to recover from biliary troubles by careful and vigorous management with biliary endoscopic intervention, and were able to continue sorafenib therapy safely. \r\n\r\n Conclusions: Our present results suggest that sorafenib might have potential therapeutic efficacy and safety in advanced HCC patients with bile duct invasion. In case of biliary tract troubles before and during sorafenib treatment, early biliary management may be important to continue sorafenib therapy safely. Further studies are needed to confirm the outcomes of sorafenib in advanced HCC patients with bile duct invasion. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors gallbladder cancer laparoscopy era iatrogenic bile spillage worsens prognosis purpose hepatobiliary surgery changed dramatically recent decades advent laparoscopic techniques aim retrospective study compare survival rates according stages adjusting important prognostic factors methods retrospective study 17 year period january 1994 april 2011 carried cases studied divided two time period cohorts treated first 9 years n 109 treated last 7 years n 109 results operation curative intent performed 218 patients 5 year survival rates according depth invasion 86 t1 56 t2 45 t3 5 t4 number cases incidental gallbladder cancer found 3 919 laparoscopic cholecystectomies 96 2 4 incidental gallbladder cancer revealed better survival rate p 0 003 iatrogenic bile spillage found 20 perforations gallbladder laparoscopic cholecystectomies 16 preoperative percutaneous transhepatic gallbladder drainages 16 percutaneous transhepatic biliary drainages percutaneous transhepatic biliary drainage patients showed significantly lower survival rate patients without iatrogenic bile spillage p 0 034 chemoradiation appeared improve overall survival p 0 001 multivariate analysis also revealed time period type surgery surgical margin lymphovascular invasion lymph node involvement chemoradiation therapy significant effects conclusion study found prognosis gallbladder cancer still determined stage presentation due aggressive biology tumor early diagnosis radical resection appropriate adjuvant therapy increase overall survival stn","probabilities":0.9799733,"Title":"Prognostic Factors For Gallbladder Cancer In The Laparoscopy Era: Iatrogenic Bile Spillage Worsens The Prognosis","Abstract":"Purpose: Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors. \r\n\r\n Methods: A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 109). \r\n\r\n Results: An operation with curative intent was performed on 218 patients. The 5-year survival rates according to the depth of invasion were 86% (T1), 56% (T2), 45% (T3), and 5% (T4). The number of cases of incidental gallbladder cancer found during 3,919 laparoscopic cholecystectomies was 96 (2.4%). Incidental gallbladder cancer revealed a better survival rate (P = 0.003). Iatrogenic bile spillage was found in 20 perforations of the gallbladder during laparoscopic cholecystectomies, 16 preoperative percutaneous transhepatic gallbladder drainages and 16 percutaneous transhepatic biliary drainages; only percutaneous transhepatic biliary drainage patients showed a significantly lower survival rate than patients without iatrogenic bile spillage (P < 0.034). Chemoradiation appeared to improve overall survival (P < 0.001). Multivariate analysis also revealed that time period, type of surgery, surgical margin, lymphovascular invasion, lymph node involvement, and chemoradiation therapy had significant effects. \r\n\r\n Conclusion: This study found that the prognosis of gallbladder cancer is still determined by the stage at presentation due to the aggressive biology of this tumor. Early diagnosis, radical resection and appropriate adjuvant therapy can increase overall survival.","Source":"STN","category":"HUMAN","training_data":"Prognostic Factors For Gallbladder Cancer In The Laparoscopy Era: Iatrogenic Bile Spillage Worsens The Prognosis Purpose: Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors. \r\n\r\n Methods: A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 109). \r\n\r\n Results: An operation with curative intent was performed on 218 patients. The 5-year survival rates according to the depth of invasion were 86% (T1), 56% (T2), 45% (T3), and 5% (T4). The number of cases of incidental gallbladder cancer found during 3,919 laparoscopic cholecystectomies was 96 (2.4%). Incidental gallbladder cancer revealed a better survival rate (P = 0.003). Iatrogenic bile spillage was found in 20 perforations of the gallbladder during laparoscopic cholecystectomies, 16 preoperative percutaneous transhepatic gallbladder drainages and 16 percutaneous transhepatic biliary drainages; only percutaneous transhepatic biliary drainage patients showed a significantly lower survival rate than patients without iatrogenic bile spillage (P < 0.034). Chemoradiation appeared to improve overall survival (P < 0.001). Multivariate analysis also revealed that time period, type of surgery, surgical margin, lymphovascular invasion, lymph node involvement, and chemoradiation therapy had significant effects. \r\n\r\n Conclusion: This study found that the prognosis of gallbladder cancer is still determined by the stage at presentation due to the aggressive biology of this tumor. Early diagnosis, radical resection and appropriate adjuvant therapy can increase overall survival. STN","prediction_labels":"HUMAN"},{"cleaned":"expression roles lectin galactoside binding soluble 3 binding protein lgals3bp cholangiocarcinoma cell lines polypeptide n acetylgalactosaminyltransferase 6 galnt6 involved initiation o glycosylation reported play crucial roles mammary carcinogenesis binding several substrates however biological roles mediating growth promoting effects remain unknown present study demonstrated crucial pathophysiological role galnt6 o glycosylation lectin galactoside binding soluble 3 binding protein lgals3bp secreted growth promoting glycoprotein breast cancer growth cancer genome atlas data analysis revealed high expression levels galnt6 significantly associated poor prognosis breast cancer galnt6 o glycosylated lgals3bp breast cancer cells whereas knockdown galnt6 sirna led inhibition o glycosylation secretion lgals3bp resulting suppression breast cancer cell growth notably lgals3bp potentially o glycosylated three sites t556 t571 s582 galnt6 thereby promoting autocrine cell growth whereas expression lgals3bp three ala substitutions t556a t571a s582a cells drastically reduced galnt6 dependent lgals3bp o glycosylation secretion resulting suppression autocrine growth promoting effect findings present study suggest galnt6 lgals3bp axis crucial breast cancer cell proliferation may therapeutic target biomarker mammary tumors stn","probabilities":0.9467213,"Title":"Expression And Roles Of Lectin Galactoside-Binding Soluble 3 Binding Protein (Lgals3Bp) In Cholangiocarcinoma Cell Lines","Abstract":"Polypeptide N‑acetylgalactosaminyltransferase 6 (GALNT6), which is involved in the initiation of O‑glycosylation, has been reported to play crucial roles in mammary carcinogenesis through binding to several substrates; however, its biological roles in mediating growth‑promoting effects remain unknown. The present study demonstrated a crucial pathophysiological role of GALNT6 through its O‑glycosylation of lectin galactoside‑binding soluble 3 binding protein (LGALS3BP), a secreted growth‑promoting glycoprotein, in breast cancer growth. The Cancer Genome Atlas data analysis revealed that high expression levels of GALNT6 were significantly associated with poor prognosis of breast cancer. GALNT6 O‑glycosylated LGALS3BP in breast cancer cells, whereas knockdown of GALNT6 by siRNA led to the inhibition of both the O‑glycosylation and secretion of LGALS3BP, resulting in the suppression of breast cancer cell growth. Notably, LGALS3BP is potentially O‑glycosylated at three sites (T556, T571 and S582) by GALNT6, thereby promoting autocrine cell growth, whereas the expression of LGALS3BP with three Ala substitutions (T556A, T571A and S582A) in cells drastically reduced GALNT6‑dependent LGALS3BP O‑glycosylation and secretion, resulting in suppression of autocrine growth‑promoting effect. The findings of the present study suggest that the GALNT6‑LGALS3BP axis is crucial for breast cancer cell proliferation and may be a therapeutic target and biomarker for mammary tumors.","Source":"STN","category":"ANIMAL","training_data":"Expression And Roles Of Lectin Galactoside-Binding Soluble 3 Binding Protein (Lgals3Bp) In Cholangiocarcinoma Cell Lines Polypeptide N‑acetylgalactosaminyltransferase 6 (GALNT6), which is involved in the initiation of O‑glycosylation, has been reported to play crucial roles in mammary carcinogenesis through binding to several substrates; however, its biological roles in mediating growth‑promoting effects remain unknown. The present study demonstrated a crucial pathophysiological role of GALNT6 through its O‑glycosylation of lectin galactoside‑binding soluble 3 binding protein (LGALS3BP), a secreted growth‑promoting glycoprotein, in breast cancer growth. The Cancer Genome Atlas data analysis revealed that high expression levels of GALNT6 were significantly associated with poor prognosis of breast cancer. GALNT6 O‑glycosylated LGALS3BP in breast cancer cells, whereas knockdown of GALNT6 by siRNA led to the inhibition of both the O‑glycosylation and secretion of LGALS3BP, resulting in the suppression of breast cancer cell growth. Notably, LGALS3BP is potentially O‑glycosylated at three sites (T556, T571 and S582) by GALNT6, thereby promoting autocrine cell growth, whereas the expression of LGALS3BP with three Ala substitutions (T556A, T571A and S582A) in cells drastically reduced GALNT6‑dependent LGALS3BP O‑glycosylation and secretion, resulting in suppression of autocrine growth‑promoting effect. The findings of the present study suggest that the GALNT6‑LGALS3BP axis is crucial for breast cancer cell proliferation and may be a therapeutic target and biomarker for mammary tumors. STN","prediction_labels":"ANIMAL"},{"cleaned":"high dose chemoradiation unresectable hilar cholangiocarcinomas using intensity modulated external beam radiotherapy single tertiary care centre experience background present results patients diagnosed unresectable hilar cholangiocarcinomas treated high dose radiotherapy concurrent chemotherapy methods aug 2005 dec 2012 68 consecutive patients treated fifty patients group 1 presenting us obstructive jaundice planned endobiliary brachytherapy ebbt 14 gy followed external beam radiotherapy ebrt 45 gy twenty two patients group 2 previously undergone biliary drainage underwent ebrt 57 gy patients received injection gemcitabine 300 mg m2 weekly along ebrt results twenty nine patients group 1 22 patients group 2 completed treatment twenty six 55 patients achieved complete radiological response 16 64 belonging group 1 8 44 group 2 p 0 05 median overall survival mos 17 5 16 months group 1 2 respectively p 0 07 1 2 year survival 63 18 group 61 22 group ii respectively mos 5 months 1 year survival 14 patients receiving ebbt mos significantly better complete response p 0 001 conclusions intensity modulated radiotherapy imrt modulated high dose radiotherapy used either alone brachytherapy demonstrates potential prolonged overall survival unresectable hilar cholangiocarcinomas stn","probabilities":0.9799733,"Title":"High Dose Chemoradiation For Unresectable Hilar Cholangiocarcinomas Using Intensity Modulated External Beam Radiotherapy: A Single Tertiary Care Centre Experience","Abstract":"Background: We present results of patients diagnosed with unresectable hilar cholangiocarcinomas treated with high dose radiotherapy and concurrent chemotherapy. \r\n\r\n Methods: From Aug 2005 to Dec 2012, 68 consecutive patients were treated. Fifty patients (group 1) presenting to us with obstructive jaundice were planned for endobiliary brachytherapy (EBBT 14 Gy) followed external beam radiotherapy (EBRT 45 Gy). Twenty-two patients (group 2) who had previously undergone biliary drainage underwent EBRT (57 Gy). All patients received injection Gemcitabine 300 mg/m2/weekly along with EBRT. \r\n\r\n Results: Twenty-nine patients in group 1 and 22 patients in group 2 completed the treatment. Twenty-six (55%) patients achieved complete radiological response, 16 (64%) belonging to group 1 and 8 (44%) of group 2 (P=0.05). The median overall survival (MOS) was 17.5 and 16 months for group 1 and 2 respectively (P=0.07). The 1- and 2-year survival was 63%, and 18% for group I and 61% and 22% for group II respectively. The MOS was 5 months and 1 year survival was 14% for patients receiving EBBT only. MOS was significantly better after complete response (P=0.001). \r\n\r\n Conclusions: Intensity modulated radiotherapy (IMRT) modulated high dose radiotherapy used either alone or with brachytherapy demonstrates potential to prolonged overall survival in unresectable hilar cholangiocarcinomas.","Source":"STN","category":"HUMAN","training_data":"High Dose Chemoradiation For Unresectable Hilar Cholangiocarcinomas Using Intensity Modulated External Beam Radiotherapy: A Single Tertiary Care Centre Experience Background: We present results of patients diagnosed with unresectable hilar cholangiocarcinomas treated with high dose radiotherapy and concurrent chemotherapy. \r\n\r\n Methods: From Aug 2005 to Dec 2012, 68 consecutive patients were treated. Fifty patients (group 1) presenting to us with obstructive jaundice were planned for endobiliary brachytherapy (EBBT 14 Gy) followed external beam radiotherapy (EBRT 45 Gy). Twenty-two patients (group 2) who had previously undergone biliary drainage underwent EBRT (57 Gy). All patients received injection Gemcitabine 300 mg/m2/weekly along with EBRT. \r\n\r\n Results: Twenty-nine patients in group 1 and 22 patients in group 2 completed the treatment. Twenty-six (55%) patients achieved complete radiological response, 16 (64%) belonging to group 1 and 8 (44%) of group 2 (P=0.05). The median overall survival (MOS) was 17.5 and 16 months for group 1 and 2 respectively (P=0.07). The 1- and 2-year survival was 63%, and 18% for group I and 61% and 22% for group II respectively. The MOS was 5 months and 1 year survival was 14% for patients receiving EBBT only. MOS was significantly better after complete response (P=0.001). \r\n\r\n Conclusions: Intensity modulated radiotherapy (IMRT) modulated high dose radiotherapy used either alone or with brachytherapy demonstrates potential to prolonged overall survival in unresectable hilar cholangiocarcinomas. STN","prediction_labels":"HUMAN"},{"cleaned":"predictors incidental gallbladder cancer elderly patients background time diagnosis patients gallbladder cancer advanced stage cancer unresectable long term survivors usually seen small number patients incidental gallbladder cancer study aimed identify preoperative predictors incidental gallbladder cancer elderly patients methods total 4014 patients 44 years old undergone cholecystectomy department january 2000 december 2010 retrospectively reviewed univariate multivariate modalities used identify predictive factors incidental gallbladder cancer results twenty nine 4014 patients undergone cholecystectomy benign gallbladder diseases histologically diagnosed incidental gallbladder cancer multivariate analysis identified elevated carbohydrate antigen 19 9 combined carcinoembryonic antigen carbohydrate antigen 125 p 0 045 gallbladder polyp greater equal 1 2 cm p 0 043 focal gallbladder wall thickening equal 5 mm p 0 002 predictive factors incidental gallbladder cancer conclusion cholecystectomy suggested patients predictive factors intraoperative frozen section considered rule carcinoma stn","probabilities":0.9799733,"Title":"Predictors Of Incidental Gallbladder Cancer In Elderly Patients","Abstract":"Background: At the time of diagnosis, most patients with gallbladder cancer are in advanced stage and the cancer is unresectable. Long-term survivors are usually seen in a small number of patients with incidental gallbladder cancer. This study aimed to identify preoperative predictors of incidental gallbladder cancer in elderly patients. \r\n\r\n Methods: A total of 4014 patients of more than 44 years old who had undergone cholecystectomy at our department from January 2000 to December 2010 were retrospectively reviewed. Univariate and multivariate modalities were used to identify the predictive factors of incidental gallbladder cancer. \r\n\r\n Results: Twenty-nine of the 4014 patients who had undergone cholecystectomy for benign gallbladder diseases were histologically diagnosed as having incidental gallbladder cancer. Multivariate analysis identified that elevated carbohydrate antigen 19-9 combined with carcinoembryonic antigen and/or carbohydrate antigen 125 (P=0.045), a gallbladder polyp greater than or equal to 1.2 cm (P=0.043) and focal gallbladder wall thickening of more than or equal to 5 mm (P=0.002) were predictive factors of incidental gallbladder cancer. \r\n\r\n Conclusion: Cholecystectomy is suggested for patients with these predictive factors and intraoperative frozen section should be considered to rule out carcinoma.","Source":"STN","category":"HUMAN","training_data":"Predictors Of Incidental Gallbladder Cancer In Elderly Patients Background: At the time of diagnosis, most patients with gallbladder cancer are in advanced stage and the cancer is unresectable. Long-term survivors are usually seen in a small number of patients with incidental gallbladder cancer. This study aimed to identify preoperative predictors of incidental gallbladder cancer in elderly patients. \r\n\r\n Methods: A total of 4014 patients of more than 44 years old who had undergone cholecystectomy at our department from January 2000 to December 2010 were retrospectively reviewed. Univariate and multivariate modalities were used to identify the predictive factors of incidental gallbladder cancer. \r\n\r\n Results: Twenty-nine of the 4014 patients who had undergone cholecystectomy for benign gallbladder diseases were histologically diagnosed as having incidental gallbladder cancer. Multivariate analysis identified that elevated carbohydrate antigen 19-9 combined with carcinoembryonic antigen and/or carbohydrate antigen 125 (P=0.045), a gallbladder polyp greater than or equal to 1.2 cm (P=0.043) and focal gallbladder wall thickening of more than or equal to 5 mm (P=0.002) were predictive factors of incidental gallbladder cancer. \r\n\r\n Conclusion: Cholecystectomy is suggested for patients with these predictive factors and intraoperative frozen section should be considered to rule out carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"sirtuin 1 induces ciliary loss cell growth cholangiocarcinoma background loss primary cilia multisensory organelle expressed almost every cell body common occurrence solid tumors including cholangiocarcinoma cca mechanisms leading ciliary loss well consequences unclear understudied lab described deacetylation ciliary components main factor ciliary loss cca sirtuin 1 sirt1 nad dependent deacetylase histone non histone proteins aim investigate role sirt1 cilia formation cca cell growth methods assessed sirt1 expression cca patients utilizing available public databases furthermore protein expression assessed cca cell lines hucct1 kmch compared normal cholangiocytes h69 nhc western blotting analysis immunoprecipitations performed sirt1 speci c antibody interactions revealed western blots experimentally expressed sirt1 normal cholangiocyte cells pharmacological inhibition sirt1 accomplished butyrate 3mm sirtinol 10 m cells examined ciliary length frequency immuno uorescence cell proliferation assessed real time cell imaging using incucyte system results first using tcga database found sirt1 expression higher cca patients compared healthy controls consistently cca cell lines showed higher levels 4 fold p 0 005 n 3 sirt1 protein expression compared normal cholangiocytes experimental expression sirt1 normal cells lead decrease ciliary length 2 5 fold p 0 005 n 6 frequency 60 38 p 0 005 n 6 correlated decreased acetylation tubulin main component ciliary axoneme 4 6 fold p 0 005 n 3 addition found pharmacological sirt1 inhibitors signi cantly increased frequency length cilia cca cells also found sirt1 interacts ciliary proteins including ift88 arl13b kif3a tubulin tubulin co immunoprecipitation immuno uorescence methods moreover observed sirt1 induced deacetylation ciliary proteins furthermore found experimental expression sirt1 normal cells induced proliferation 40 22 p 0 001 n 50 however addition sirt1 inhibitors sirt1 expressed cells decreased cell growth finally sirt1 inhibitors reduced cca cell proliferation 36 84 p 0 0001 n 50 conclusion data suggest sirt1 overexpressed cca nduces loss primary cilia cholangiocytes mechanism involving interaction deacetylation ciliary proteins inducing cell proliferation therefore targeting sirt1 may potential new therapeutic approach cca google scholar","probabilities":0.9467213,"Title":"Sirtuin-1 Induces Ciliary Loss And Cell Growth In Cholangiocarcinoma","Abstract":"Background: The loss of primary cilia, a multisensory organelle expressed in almost every cell of the body, is a common occurrence in solid tumors, including cholangiocarcinoma (CCA). The mechanisms leading to ciliary loss as well as its consequences are unclear and understudied. Our lab has described that the deacetylation of ciliary components is the main factor for ciliary loss in CCA. Sirtuin-1 (SIRT1) is a NAD-dependent deacetylase for histone and non-histone proteins. Our aim is to investigate the role of SIRT1 on cilia formation and CCA cell growth. Methods: We assessed SIRT1 expression in CCA patients utilizing the available public databases. Furthermore, the protein expression was assessed in the CCA cell lines HuCCT1 and KMCH compared to the normal cholangiocytes H69 and NHC by western blotting analysis. Immunoprecipitations were performed with a SIRT1 specic antibody, and interactions were revealed by western blots. We had experimentally over-expressed SIRT1 in normal cholangiocyte cells. Pharmacological inhibition of SIRT1 was accomplished by butyrate (3mM) or Sirtinol (10μM). Cells were examined for ciliary length and frequency by immunouorescence. Cell proliferation was assessed by real-time cell imaging using the IncuCyte system. Results: First, using the TCGA database we found that SIRT1 expression is higher in CCA patients compared to the healthy controls. Consistently, the CCA cell lines showed higher levels (4 fold, p˂0.005, n=3) of SIRT1 protein expression compared to normal cholangiocytes. The experimental over-expression of SIRT1 in normal cells lead to a decrease in ciliary length (2.5 fold, p˂0.005, n=6) and frequency (60.38% p˂0.005, n=6), which correlated with decreased acetylation of α-tubulin, the main component of the ciliary axoneme (4.6 fold p˂0.005, n=3). In addition, we found that the pharmacological SIRT1 inhibitors signicantly increased the frequency and length of cilia in CCA cells. We also found that SIRT1 interacts with ciliary proteins, including IFT88, ARL13B, KiF3A, γ-Tubulin, and α-Tubulin by co-immunoprecipitation and immunouorescence methods. Moreover, we observed that SIRT1 induced the deacetylation of these ciliary proteins. Furthermore, we found the experimental over-expression of SIRT1 in normal cells induced proliferation (40.22 % p˂0.001, n=50). However, addition of the SIRT1 inhibitors to the SIRT1 over-expressed cells decreased cell growth. Finally, SIRT1 inhibitors reduced CCA cell proliferation (36.84% p˂0.0001, n=50). Conclusion: Our data suggest that SIRT1 is overexpressed in CCA and nduces the loss of primary cilia in cholangiocytes by a mechanism involving interaction and deacetylation of ciliary proteins, inducing cell proliferation. Therefore, targeting of SIRT1 may be a potential new therapeutic approach for CCA","Source":"Google Scholar","category":"ANIMAL","training_data":"Sirtuin-1 Induces Ciliary Loss And Cell Growth In Cholangiocarcinoma Background: The loss of primary cilia, a multisensory organelle expressed in almost every cell of the body, is a common occurrence in solid tumors, including cholangiocarcinoma (CCA). The mechanisms leading to ciliary loss as well as its consequences are unclear and understudied. Our lab has described that the deacetylation of ciliary components is the main factor for ciliary loss in CCA. Sirtuin-1 (SIRT1) is a NAD-dependent deacetylase for histone and non-histone proteins. Our aim is to investigate the role of SIRT1 on cilia formation and CCA cell growth. Methods: We assessed SIRT1 expression in CCA patients utilizing the available public databases. Furthermore, the protein expression was assessed in the CCA cell lines HuCCT1 and KMCH compared to the normal cholangiocytes H69 and NHC by western blotting analysis. Immunoprecipitations were performed with a SIRT1 specic antibody, and interactions were revealed by western blots. We had experimentally over-expressed SIRT1 in normal cholangiocyte cells. Pharmacological inhibition of SIRT1 was accomplished by butyrate (3mM) or Sirtinol (10μM). Cells were examined for ciliary length and frequency by immunouorescence. Cell proliferation was assessed by real-time cell imaging using the IncuCyte system. Results: First, using the TCGA database we found that SIRT1 expression is higher in CCA patients compared to the healthy controls. Consistently, the CCA cell lines showed higher levels (4 fold, p˂0.005, n=3) of SIRT1 protein expression compared to normal cholangiocytes. The experimental over-expression of SIRT1 in normal cells lead to a decrease in ciliary length (2.5 fold, p˂0.005, n=6) and frequency (60.38% p˂0.005, n=6), which correlated with decreased acetylation of α-tubulin, the main component of the ciliary axoneme (4.6 fold p˂0.005, n=3). In addition, we found that the pharmacological SIRT1 inhibitors signicantly increased the frequency and length of cilia in CCA cells. We also found that SIRT1 interacts with ciliary proteins, including IFT88, ARL13B, KiF3A, γ-Tubulin, and α-Tubulin by co-immunoprecipitation and immunouorescence methods. Moreover, we observed that SIRT1 induced the deacetylation of these ciliary proteins. Furthermore, we found the experimental over-expression of SIRT1 in normal cells induced proliferation (40.22 % p˂0.001, n=50). However, addition of the SIRT1 inhibitors to the SIRT1 over-expressed cells decreased cell growth. Finally, SIRT1 inhibitors reduced CCA cell proliferation (36.84% p˂0.0001, n=50). Conclusion: Our data suggest that SIRT1 is overexpressed in CCA and nduces the loss of primary cilia in cholangiocytes by a mechanism involving interaction and deacetylation of ciliary proteins, inducing cell proliferation. Therefore, targeting of SIRT1 may be a potential new therapeutic approach for CCA Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"inflammation based prognostic score useful predictor postoperative outcome patients extrahepatic cholangiocarcinoma background purpose recent studies revealed glasgow prognostic score gps inflammation based prognostic score useful predicting outcome variety cancers study sought investigate significance gps prognostication patients underwent surgery extrahepatic cholangiocarcinoma methods retrospectively analyzed total 62 patients underwent resection extrahepatic cholangiocarcinoma calculated gps follows patients elevated c reactive protein 10 mg l hypoalbuminemia 35 g l allocated score 2 patients one none abnormalities allocated ore 1 0 respectively prognostic significance analyzed log rank test cox proportional hazards model results overall survival rate 25 5 5 years 62 patients venous invasion p 0 01 pathological primary tumor category p 0 013 lymph node metastasis category p 0 001 tnm stage p 0 001 gps p 0 008 significantly associated survival univariate analysis cox model demonstrated increased gps independent predictive factor poor prognosis conclusions preoperative gps useful predictor postoperative outcome patients extrahepatic cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Inflammation-based prognostic score is a useful predictor of postoperative outcome in patients with extrahepatic cholangiocarcinoma","Abstract":"BACKGROUND/PURPOSE: Recent studies have revealed that the Glasgow prognostic score (GPS), an inflammation-based prognostic score, is useful for predicting outcome in a variety of cancers. This study sought to investigate the significance of GPS for prognostication of patients who underwent surgery with extrahepatic cholangiocarcinoma. METHODS: We retrospectively analyzed a total of 62 patients who underwent resection for extrahepatic cholangiocarcinoma. We calculated the GPS as follows: patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2; patients with one or none of these abnormalities were allocated a s ore of 1 or 0, respectively. Prognostic significance was analyzed by the log-rank test and a Cox proportional hazards model. RESULTS: Overall survival rate was 25.5 % at 5 years for all 62 patients. Venous invasion (p = 0.01), pathological primary tumor category (p = 0.013), lymph node metastasis category (p < 0.001), TNM stage (p < 0.001), and GPS (p = 0.008) were significantly associated with survival by univariate analysis. A Cox model demonstrated that increased GPS was an independent predictive factor with poor prognosis. CONCLUSIONS: The preoperative GPS is a useful predictor of postoperative outcome in patients with extrahepatic cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Inflammation-based prognostic score is a useful predictor of postoperative outcome in patients with extrahepatic cholangiocarcinoma BACKGROUND/PURPOSE: Recent studies have revealed that the Glasgow prognostic score (GPS), an inflammation-based prognostic score, is useful for predicting outcome in a variety of cancers. This study sought to investigate the significance of GPS for prognostication of patients who underwent surgery with extrahepatic cholangiocarcinoma. METHODS: We retrospectively analyzed a total of 62 patients who underwent resection for extrahepatic cholangiocarcinoma. We calculated the GPS as follows: patients with both an elevated C-reactive protein (>10 mg/L) and hypoalbuminemia (<35 g/L) were allocated a score of 2; patients with one or none of these abnormalities were allocated a s ore of 1 or 0, respectively. Prognostic significance was analyzed by the log-rank test and a Cox proportional hazards model. RESULTS: Overall survival rate was 25.5 % at 5 years for all 62 patients. Venous invasion (p = 0.01), pathological primary tumor category (p = 0.013), lymph node metastasis category (p < 0.001), TNM stage (p < 0.001), and GPS (p = 0.008) were significantly associated with survival by univariate analysis. A Cox model demonstrated that increased GPS was an independent predictive factor with poor prognosis. CONCLUSIONS: The preoperative GPS is a useful predictor of postoperative outcome in patients with extrahepatic cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative prediction survival resectable gallbladder cancer combined utilization ca 19 9 carcinoembryonic antigen background currently frequently used staging systems gallbladder cancer gbc based postoperative pathological examinations patients undergoing curative operation effective method predict survival preoperatively study explored whether combined utilization two tumor biomarkers namely carbohydrate antigen 19 9 ca 19 9 carcinoembryonic antigen cea give preoperative prediction survival resectable gbc methods seventy three patients underwent radical resection gbc included study retrospective analysis clinical pathological data conducted results multivariate analysis ca 19 9 elevation p 0 05 cea elevation p 0 001 discovered two individual factors postoperative survival combined utilization patients divided three groups patients elevation cea group patients elevation ca 19 9 without cea group ii patients nonelevations either ca 19 9 cea group iii cumulative 5 year survival rates groups ii iii 0 14 0 42 8 respectively p 0 05 conclusions combined utilization ca 19 9 cea individualized prediction survival available resectable gbc operation extended radical operation brings prognostic benefits patients nonelevations either ca 19 9 cea however operation larger scale destructive manner careful consideration surgical decisions made patients elevation tumor biomarkers especially cea pubmed","probabilities":0.9799733,"Title":"Preoperative prediction of survival in resectable gallbladder cancer by a combined utilization of CA 19-9 and carcinoembryonic antigen","Abstract":"BACKGROUND: Currently, all frequently used staging systems in gallbladder cancer (GBC) are based on postoperative pathological examinations. In patients undergoing curative operation, there is no effective method to predict survival preoperatively. In this study, we explored whether a combined utilization of two tumor biomarkers, namely carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA), could give a preoperative prediction of survival in resectable GBC. METHODS: Seventy-three patients who underwent radical resection for GBC were included in this study. A retrospective analysis of clinical-pathological data was conducted. RESULTS: By multivariate analysis, CA 19-9 elevation (P < 0.05) and CEA elevation (P < 0.001) were discovered as two individual factors for postoperative survival. By a combined utilization, patients were divided into three groups: patients with elevation of CEA (group I), patients with elevation of CA 19-9 but without CEA (group II), and patients with nonelevations of either CA 19-9 or CEA (group III). The cumulative 5-year survival rates in groups I, II, and III were 0, 14.0%, and 42.8%, respectively (P < 0.05). CONCLUSIONS: By a combined utilization of CA 19-9 and CEA, individualized prediction of survival is available in resectable GBC before operation. Extended radical operation brings the most prognostic benefits in patients with nonelevations of either CA 19-9 or CEA. However, if operation would be in a larger-scale destructive manner, careful consideration of surgical decisions should be made in patients with elevation of tumor biomarkers, especially CEA.","Source":"PubMed","category":"HUMAN","training_data":"Preoperative prediction of survival in resectable gallbladder cancer by a combined utilization of CA 19-9 and carcinoembryonic antigen BACKGROUND: Currently, all frequently used staging systems in gallbladder cancer (GBC) are based on postoperative pathological examinations. In patients undergoing curative operation, there is no effective method to predict survival preoperatively. In this study, we explored whether a combined utilization of two tumor biomarkers, namely carbohydrate antigen 19-9 (CA 19-9) and carcinoembryonic antigen (CEA), could give a preoperative prediction of survival in resectable GBC. METHODS: Seventy-three patients who underwent radical resection for GBC were included in this study. A retrospective analysis of clinical-pathological data was conducted. RESULTS: By multivariate analysis, CA 19-9 elevation (P < 0.05) and CEA elevation (P < 0.001) were discovered as two individual factors for postoperative survival. By a combined utilization, patients were divided into three groups: patients with elevation of CEA (group I), patients with elevation of CA 19-9 but without CEA (group II), and patients with nonelevations of either CA 19-9 or CEA (group III). The cumulative 5-year survival rates in groups I, II, and III were 0, 14.0%, and 42.8%, respectively (P < 0.05). CONCLUSIONS: By a combined utilization of CA 19-9 and CEA, individualized prediction of survival is available in resectable GBC before operation. Extended radical operation brings the most prognostic benefits in patients with nonelevations of either CA 19-9 or CEA. However, if operation would be in a larger-scale destructive manner, careful consideration of surgical decisions should be made in patients with elevation of tumor biomarkers, especially CEA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role photodynamic therapy hilar cholangiocarcinoma prognosis hilar cholangiocarcinoma limited tumor spread along biliary tree leading refractory obstructive cholestasis cholangitis liver failure palliation biliary endoprostheses results median survival times 4 6 months advanced bile duct cancer photodynamic therapy pdt local photochemical tumor treatment consisting photosensitizing agent combined laser irradiation distinct wavelength tumor ablation pdt combined biliary stenting reduces cholestasis significantly improves median survival time however treatment widely available photosensitizers used pdt cause prolonged photosensitivity optimum control tumor spread along bile ducts control cholestasis cholangitis prolong survival one two thirds patients renders suitable antitumor therapies pubmed","probabilities":0.9799733,"Title":"The role of photodynamic therapy for hilar cholangiocarcinoma","Abstract":"The prognosis for hilar cholangiocarcinoma is limited by tumor spread along the biliary tree leading to refractory obstructive cholestasis, cholangitis, and liver failure. Palliation with biliary endoprostheses results in median survival times of 4-6 months for advanced bile duct cancer. Photodynamic therapy (PDT) is a local photochemical tumor treatment consisting of a photosensitizing agent combined with laser irradiation of a distinct wavelength. Tumor ablation with PDT combined with biliary stenting reduces cholestasis and significantly improves median survival time. However, the treatment is not widely available, and the photosensitizers used for PDT cause prolonged photosensitivity. Optimum control of tumor spread along the bile ducts and control of cholestasis and cholangitis will prolong survival in one to two thirds of patients, and renders them suitable for other antitumor therapies.","Source":"PubMed","category":"HUMAN","training_data":"The role of photodynamic therapy for hilar cholangiocarcinoma The prognosis for hilar cholangiocarcinoma is limited by tumor spread along the biliary tree leading to refractory obstructive cholestasis, cholangitis, and liver failure. Palliation with biliary endoprostheses results in median survival times of 4-6 months for advanced bile duct cancer. Photodynamic therapy (PDT) is a local photochemical tumor treatment consisting of a photosensitizing agent combined with laser irradiation of a distinct wavelength. Tumor ablation with PDT combined with biliary stenting reduces cholestasis and significantly improves median survival time. However, the treatment is not widely available, and the photosensitizers used for PDT cause prolonged photosensitivity. Optimum control of tumor spread along the bile ducts and control of cholestasis and cholangitis will prolong survival in one to two thirds of patients, and renders them suitable for other antitumor therapies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"adipocytes promote cholangiocarcinoma metastasis fatty acid binding protein 4 background early occurrence regional nodal distant metastases cholangiocarcinoma cca one major reasons poor prognosis however related mechanisms largely elusive recently increasing evidences indicate adipocytes might involved proliferation homing migration invasion several malignancies present study attempt determine effects possible mechanisms adipocytes regulating progression cca methods adipocyte cca cell co culture system cca metastasis mice model used determine effects adipocytes cca metastasis identified biological functions possible mechanisms adipocyte derived fatty acid binding protein 4 fabp4 regulating adipocyte induced cca metastasis epithelial mesenchymal transition emt phenotypes vitro vivo results adipocyte cca cell co culture promotes vitro vivo tumor metastasis leading increased adipocyte derived fatty acid absorbance intracellular lipids cca cells indicates adipocytes might function energy source cca progression providing free fatty acids highly expressed fabp4 protein identified adipose tissues fully differentiated adipocytes upregulated fabp4 also detected qrt pcr assay cca cells co cultivated adipose extracts compared parental cca cells specific fabp4 inhibitor bms309403 significantly impaired adipocyte induced cca metastasis emt phenotypes vitro vivo conclusions together results demonstrate adipocyte cca interaction energy extraction cca cells adipocytes crucial invasion migration emt cca cells fabp4 adipocytes mediates adipocyte induced variations cca cells serve potential target treatment cca stn","probabilities":0.9467213,"Title":"Adipocytes Promote Cholangiocarcinoma Metastasis Through Fatty Acid Binding Protein 4","Abstract":"Background: The early occurrence regional nodal and distant metastases cholangiocarcinoma (CCA) is one of the major reasons for its poor prognosis. However, the related mechanisms are largely elusive. Recently, increasing evidences indicate that adipocytes might be involved in the proliferation, homing, migration and invasion of several malignancies. In the present study, we attempt to determine the effects and possible mechanisms of adipocytes on regulating progression of CCA. \r\n\r\n Methods: Adipocyte-CCA cell co-culture system and CCA metastasis mice model were used to determine the effects of adipocytes on CCA metastasis. We identified the biological functions and possible mechanisms of adipocyte-derived fatty acid binding protein 4 (FABP4) in regulating the adipocyte-induced CCA metastasis and epithelial-mesenchymal transition (EMT) phenotypes, both in vitro and in vivo. \r\n\r\n Results: Adipocyte-CCA cell co-culture promotes the in vitro and in vivo tumor metastasis, leading to increased adipocyte-derived fatty acid absorbance and intracellular lipids of CCA cells, which indicates adipocytes might function as the energy source for CCA progression by providing free fatty acids. Further, highly expressed FABP4 protein was identified in adipose tissues and fully differentiated adipocytes, and upregulated FABP4 was also detected by qRT-PCR assay in CCA cells co-cultivated with adipose extracts as compared to parental CCA cells. The specific FABP4 inhibitor BMS309403 significantly impaired adipocyte-induced CCA metastasis and EMT phenotypes both in vitro and in vivo. \r\n\r\n Conclusions: Together, the results demonstrate that the adipocyte-CCA interaction and the energy extraction of CCA cells from adipocytes are crucial for the invasion, migration and EMT of CCA cells. FABP4 from adipocytes mediates these adipocyte-induced variations in CCA cells, which could serve as a potential target for the treatment of CCA.","Source":"STN","category":"ANIMAL","training_data":"Adipocytes Promote Cholangiocarcinoma Metastasis Through Fatty Acid Binding Protein 4 Background: The early occurrence regional nodal and distant metastases cholangiocarcinoma (CCA) is one of the major reasons for its poor prognosis. However, the related mechanisms are largely elusive. Recently, increasing evidences indicate that adipocytes might be involved in the proliferation, homing, migration and invasion of several malignancies. In the present study, we attempt to determine the effects and possible mechanisms of adipocytes on regulating progression of CCA. \r\n\r\n Methods: Adipocyte-CCA cell co-culture system and CCA metastasis mice model were used to determine the effects of adipocytes on CCA metastasis. We identified the biological functions and possible mechanisms of adipocyte-derived fatty acid binding protein 4 (FABP4) in regulating the adipocyte-induced CCA metastasis and epithelial-mesenchymal transition (EMT) phenotypes, both in vitro and in vivo. \r\n\r\n Results: Adipocyte-CCA cell co-culture promotes the in vitro and in vivo tumor metastasis, leading to increased adipocyte-derived fatty acid absorbance and intracellular lipids of CCA cells, which indicates adipocytes might function as the energy source for CCA progression by providing free fatty acids. Further, highly expressed FABP4 protein was identified in adipose tissues and fully differentiated adipocytes, and upregulated FABP4 was also detected by qRT-PCR assay in CCA cells co-cultivated with adipose extracts as compared to parental CCA cells. The specific FABP4 inhibitor BMS309403 significantly impaired adipocyte-induced CCA metastasis and EMT phenotypes both in vitro and in vivo. \r\n\r\n Conclusions: Together, the results demonstrate that the adipocyte-CCA interaction and the energy extraction of CCA cells from adipocytes are crucial for the invasion, migration and EMT of CCA cells. FABP4 from adipocytes mediates these adipocyte-induced variations in CCA cells, which could serve as a potential target for the treatment of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"role embryonic protein sox2 cholangiocarcinoma sox2 overexpression correlates aggressive behavior poor overall survival cholangiocarcinoma cca however cellular functions precise role sox2 cca elucidated inserted sox2 coding sequence establish caa cell line stably overexpressed sox2 vitro experiments showed overexpression sox2 cells associated increased cell proliferation suppressed cell apoptosis well enhanced cell migration invasion findings may lead better understanding biological effect sox2 provide mechanistic insights developing potential therapeutic strategies cca treatment google scholar","probabilities":0.9467213,"Title":"Role Of The Embryonic Protein Sox2 In Cholangiocarcinoma","Abstract":"SOX2 overexpression correlates with aggressive behavior and poor overall survival in cholangiocarcinoma (CCA). However, the cellular functions and precise role of SOX2 in CCA have not been elucidated. Here, we inserted SOX2 coding sequence to establish a CAA cell line which stably overexpressed SOX2. In vitro experiments showed that overexpression of SOX2 in cells was associated with increased cell proliferation, suppressed cell apoptosis, as well as enhanced cell migration and invasion. Our findings may lead to a better understanding of the biological effect of SOX2 and provide mechanistic insights for developing potential therapeutic strategies for CCA treatment.","Source":"Google Scholar","category":"ANIMAL","training_data":"Role Of The Embryonic Protein Sox2 In Cholangiocarcinoma SOX2 overexpression correlates with aggressive behavior and poor overall survival in cholangiocarcinoma (CCA). However, the cellular functions and precise role of SOX2 in CCA have not been elucidated. Here, we inserted SOX2 coding sequence to establish a CAA cell line which stably overexpressed SOX2. In vitro experiments showed that overexpression of SOX2 in cells was associated with increased cell proliferation, suppressed cell apoptosis, as well as enhanced cell migration and invasion. Our findings may lead to a better understanding of the biological effect of SOX2 and provide mechanistic insights for developing potential therapeutic strategies for CCA treatment. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"diabetes mellitus risk cholangiocarcinoma updated meta analysis introduction number studies shown diabetes mellitus implicated susceptibility several cancers however relationship diabetes cholangiocarcinoma remain unclear aim quantitatively assess relationship diabetes incidence cholangiocarcinoma cohort case control studies material methods literature search performed entries 1996 2014 using pubmed embase databases studies included reported odds ratios corresponding 95 ci cholangiocarcinoma respect diabetes mellitus results twenty studies met inclusion criteria included fifteen case control studies five cohort studies asia n 11 united states n 5 europe n 4 compared individuals without diabetes pooled cholangiocarcinoma 1 74 95 ci 1 62 1 87 p 0 568 heterogeneity patients diabetes icc summary rr 1 93 95 ci 1 65 2 25 p 0 037 heterogeneity ecc summary rr 1 66 95 ci 1 39 1 98 p 0 001 heterogeneity funnel plot revealed evidence publication bias concerning diabetes risk cc including icc ecc conclusions findings meta analysis suggest diabetes may increase risk cholangiocarcinoma relationship needs confirmed follow studies stn","probabilities":0.9799733,"Title":"Diabetes Mellitus And The Risk Of Cholangiocarcinoma: An Updated Meta-Analysis","Abstract":"Introduction: A number of studies have shown that diabetes mellitus is implicated in susceptibility to several cancers. However, the relationship between diabetes and cholangiocarcinoma remain unclear. \r\n\r\n Aim: To quantitatively assess the relationship between diabetes and incidence of cholangiocarcinoma in cohort and case-control studies. \r\n\r\n Material and methods: A literature search was performed for entries from 1996 to 2014 using the PubMed and EMBASE databases. Studies were included if they reported odds ratios (OR) and corresponding 95% CI of cholangiocarcinoma with respect to diabetes mellitus. \r\n\r\n Results: Twenty studies met the inclusion criteria, which included fifteen case-control studies and five cohort studies from Asia (n = 11), the United States (n = 5), and Europe (n = 4). Compared with individuals without diabetes, the pooled OR of cholangiocarcinoma was 1.74 (95% CI: 1.62-1.87, p = 0.568 for heterogeneity) for patients with diabetes, ICC (summary RR, 1.93; 95% CI: 1.65-2.25; p = 0.037 for heterogeneity), and ECC (summary RR, 1.66; 95% CI: 1.39-1.98; p = 0.001 for heterogeneity). The funnel plot revealed no evidence for publication bias concerning diabetes and the risk of CC (including ICC and ECC). \r\n\r\n Conclusions: The findings from this meta-analysis suggest that diabetes may increase the risk of cholangiocarcinoma. This relationship needs to be confirmed by further follow-up studies.","Source":"STN","category":"HUMAN","training_data":"Diabetes Mellitus And The Risk Of Cholangiocarcinoma: An Updated Meta-Analysis Introduction: A number of studies have shown that diabetes mellitus is implicated in susceptibility to several cancers. However, the relationship between diabetes and cholangiocarcinoma remain unclear. \r\n\r\n Aim: To quantitatively assess the relationship between diabetes and incidence of cholangiocarcinoma in cohort and case-control studies. \r\n\r\n Material and methods: A literature search was performed for entries from 1996 to 2014 using the PubMed and EMBASE databases. Studies were included if they reported odds ratios (OR) and corresponding 95% CI of cholangiocarcinoma with respect to diabetes mellitus. \r\n\r\n Results: Twenty studies met the inclusion criteria, which included fifteen case-control studies and five cohort studies from Asia (n = 11), the United States (n = 5), and Europe (n = 4). Compared with individuals without diabetes, the pooled OR of cholangiocarcinoma was 1.74 (95% CI: 1.62-1.87, p = 0.568 for heterogeneity) for patients with diabetes, ICC (summary RR, 1.93; 95% CI: 1.65-2.25; p = 0.037 for heterogeneity), and ECC (summary RR, 1.66; 95% CI: 1.39-1.98; p = 0.001 for heterogeneity). The funnel plot revealed no evidence for publication bias concerning diabetes and the risk of CC (including ICC and ECC). \r\n\r\n Conclusions: The findings from this meta-analysis suggest that diabetes may increase the risk of cholangiocarcinoma. This relationship needs to be confirmed by further follow-up studies. STN","prediction_labels":"HUMAN"},{"cleaned":"association metabolic syndrome hepatobiliary cancers case control study background incidence hepatobiliary cancer steadily increasing unclear rise related increasing trends obesity metabolic syndrome lifestyle changes methods case control study performed using health improvement network thin database cases diagnosis liver bile duct gallbladder cancers matched 1 2 fashion controls analyzed potential associations hepatobiliary cancer obesity metabolic syndrome results four thousand two hundred eighty seven patients 62 male 38 female hepatobiliary cancers matched 8574 controls univariate analysis body mass index bmi smoking diabetes alcohol consumption ischemic heart disease hypertension associated hepatobiliary cancer statin use non smoking status inverse association multivariate analysis bmi diabetes hypertension ischemic heart disease insulin use associated risk hepatobiliary cancer statin use non smoking status protective modeling bmi diabetes hypertension single covariate significant association hepatobiliary cancer 1 59 1 49 1 69 p 0 001 persisted despite adjusting increasing age 1 006 1005 1 006 p 0 001 background liver cirrhosis 1 037 1 03 1 044 p 0 001 conclusions obesity metabolic syndrome associated risk hepatobiliary cancer statin use seems protective pubmed","probabilities":0.9799733,"Title":"Association between metabolic syndrome and hepatobiliary cancers: A case-control study","Abstract":"BACKGROUND: The incidence of hepatobiliary cancer is steadily increasing. It is unclear if this rise is related to increasing trends in obesity, metabolic syndrome, and lifestyle changes. METHODS: A case-control study was performed using the Health Improvement Network (THIN) database. Cases with a diagnosis of liver, bile duct, and gallbladder cancers were matched in a 1:2 fashion with controls and analyzed for potential associations between hepatobiliary cancer and obesity/metabolic syndrome. RESULTS: Four thousand two hundred and eighty-seven patients (62% male, 38% female) with hepatobiliary cancers were matched with 8574 controls. On univariate analysis, body mass index (BMI), smoking, diabetes, alcohol consumption, ischemic heart disease, and hypertension were associated with hepatobiliary cancer. Statin use and non-smoking status had an inverse association. On multivariate analysis, BMI, diabetes, hypertension, ischemic heart disease, and insulin use were associated with the risk of hepatobiliary cancer. Statin use and non-smoking status were protective. On modeling BMI, each of diabetes and hypertension as a single covariate, there was a significant association with hepatobiliary cancer (1.59 [1.49-1.69], p < 0.001) which persisted despite adjusting for increasing age (1.006 [1005-1.006], p < 0.001) and background liver cirrhosis (1.037 [1.03-1.044], p < 0.001). CONCLUSIONS: Obesity and metabolic syndrome are associated with the risk of hepatobiliary cancer. Statin use seems to be protective.","Source":"PubMed","category":"HUMAN","training_data":"Association between metabolic syndrome and hepatobiliary cancers: A case-control study BACKGROUND: The incidence of hepatobiliary cancer is steadily increasing. It is unclear if this rise is related to increasing trends in obesity, metabolic syndrome, and lifestyle changes. METHODS: A case-control study was performed using the Health Improvement Network (THIN) database. Cases with a diagnosis of liver, bile duct, and gallbladder cancers were matched in a 1:2 fashion with controls and analyzed for potential associations between hepatobiliary cancer and obesity/metabolic syndrome. RESULTS: Four thousand two hundred and eighty-seven patients (62% male, 38% female) with hepatobiliary cancers were matched with 8574 controls. On univariate analysis, body mass index (BMI), smoking, diabetes, alcohol consumption, ischemic heart disease, and hypertension were associated with hepatobiliary cancer. Statin use and non-smoking status had an inverse association. On multivariate analysis, BMI, diabetes, hypertension, ischemic heart disease, and insulin use were associated with the risk of hepatobiliary cancer. Statin use and non-smoking status were protective. On modeling BMI, each of diabetes and hypertension as a single covariate, there was a significant association with hepatobiliary cancer (1.59 [1.49-1.69], p < 0.001) which persisted despite adjusting for increasing age (1.006 [1005-1.006], p < 0.001) and background liver cirrhosis (1.037 [1.03-1.044], p < 0.001). CONCLUSIONS: Obesity and metabolic syndrome are associated with the risk of hepatobiliary cancer. Statin use seems to be protective. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatectomy simultaneous resection portal vein hepatic artery advanced perihilar cholangiocarcinoma audit 50 consecutive cases objective outline experience hepatectomy simultaneous resection portal vein hepatic artery advanced perihilar cholangiocarcinoma discuss clinical significance challenging hepatectomy summary background data authors reported negative results surgery limited number patients methods retrospectively reviewed medical records 50 patients advanced cholangiocarcinoma underwent hepatectomy left trisectionectomy 26 left hepatectomy 23 right hepatectomy 1 simultaneous resection reconstruction portal vein hepatic artery focusing surgical outcome survival results operative time 776 191 minutes blood loss 2593 1890 ml time vessel resection reconstruction 25 19 minutes portal vein 119 56 minutes hepatic artery total 27 54 0 patients developed several kinds complications including intra abdominal abscess n 13 wound infection n 9 bile leakage liver stump n 9 liver failure n 7 relaparotomy necessary 5 10 0 patients one 2 0 patient died postoperative complication microscopic cancer invasion resected portal vein found 44 88 0 patients resected hepatic artery found 27 54 0 distal bile duct margin proximal bile duct margin radial margin positive cancer 2 4 0 4 8 0 17 34 0 patients respectively consequently r0 resection achieved 33 66 0 patients 1 3 5 year survival rates 78 9 36 3 30 3 respectively survival 30 patients pm0 disease underwent r0 resection better 40 7 3 5 year time points conclusion major hepatectomy simultaneous resection reconstruction portal vein hepatic artery technically demanding however surgery performed acceptable mortality experienced surgeon offers better chance long term survival selected patients pubmed","probabilities":0.9799733,"Title":"Hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma: an audit of 50 consecutive cases","Abstract":"OBJECTIVE: To outline our experience with hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma, and to discuss the clinical significance of this challenging hepatectomy. SUMMARY BACKGROUND DATA: Only a few authors reported negative results for this surgery in a very limited number of patients. METHODS: We retrospectively reviewed medical records of 50 patients with advanced cholangiocarcinoma who underwent hepatectomy (left trisectionectomy in 26, left hepatectomy in 23, and right hepatectomy in 1) with simultaneous resection and reconstruction of the portal vein and hepatic artery, focusing on surgical outcome and survival. RESULTS: The operative time was 776 +/- 191 minutes, and blood loss was 2593 +/- 1890 mL. Time of vessel resection and reconstruction was 25 +/- 19 minutes for the portal vein and 119 +/- 56 minutes for the hepatic artery. A total of 27 (54.0%) patients developed several kinds of complications, including intra-abdominal abscess (n = 13), wound infection (n = 9), bile leakage from liver stump (n = 9), and liver failure (n = 7). Relaparotomy was necessary in 5 (10.0%) patients. One (2.0%) patient died of a postoperative complication. Microscopic cancer invasion of the resected portal vein was found in 44 (88.0%) patients, while that of the resected hepatic artery was found in 27 (54.0%). The distal bile duct margin, proximal bile duct margin, and radial margin were positive for cancer in 2 (4.0%), 4 (8.0%), and 17 (34.0%) patients, respectively. Consequently, R0 resection was achieved in 33 (66.0%) patients. The 1-, 3-, and 5-year survival rates were 78.9%, 36.3%, and 30.3%, respectively. Survival for 30 patients with pM0 disease who underwent R0 resection was better, being 40.7% at the 3- and 5-year time points. CONCLUSION: Major hepatectomy with simultaneous resection and reconstruction of the portal vein and hepatic artery is technically demanding. However, this surgery can be performed with acceptable mortality by an experienced surgeon and offers a better chance of long-term survival in selected patients.","Source":"PubMed","category":"HUMAN","training_data":"Hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma: an audit of 50 consecutive cases OBJECTIVE: To outline our experience with hepatectomy with simultaneous resection of the portal vein and hepatic artery for advanced perihilar cholangiocarcinoma, and to discuss the clinical significance of this challenging hepatectomy. SUMMARY BACKGROUND DATA: Only a few authors reported negative results for this surgery in a very limited number of patients. METHODS: We retrospectively reviewed medical records of 50 patients with advanced cholangiocarcinoma who underwent hepatectomy (left trisectionectomy in 26, left hepatectomy in 23, and right hepatectomy in 1) with simultaneous resection and reconstruction of the portal vein and hepatic artery, focusing on surgical outcome and survival. RESULTS: The operative time was 776 +/- 191 minutes, and blood loss was 2593 +/- 1890 mL. Time of vessel resection and reconstruction was 25 +/- 19 minutes for the portal vein and 119 +/- 56 minutes for the hepatic artery. A total of 27 (54.0%) patients developed several kinds of complications, including intra-abdominal abscess (n = 13), wound infection (n = 9), bile leakage from liver stump (n = 9), and liver failure (n = 7). Relaparotomy was necessary in 5 (10.0%) patients. One (2.0%) patient died of a postoperative complication. Microscopic cancer invasion of the resected portal vein was found in 44 (88.0%) patients, while that of the resected hepatic artery was found in 27 (54.0%). The distal bile duct margin, proximal bile duct margin, and radial margin were positive for cancer in 2 (4.0%), 4 (8.0%), and 17 (34.0%) patients, respectively. Consequently, R0 resection was achieved in 33 (66.0%) patients. The 1-, 3-, and 5-year survival rates were 78.9%, 36.3%, and 30.3%, respectively. Survival for 30 patients with pM0 disease who underwent R0 resection was better, being 40.7% at the 3- and 5-year time points. CONCLUSION: Major hepatectomy with simultaneous resection and reconstruction of the portal vein and hepatic artery is technically demanding. However, this surgery can be performed with acceptable mortality by an experienced surgeon and offers a better chance of long-term survival in selected patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors scoring model survival metastatic biliary tract cancer purpose metastatic biliary tract cancer mbtc dismal prognosis study independent dataset patients mbtc used implement validate routine clinico laboratory parameter based scoring model risk group identification materials methods september 2006 february 2015 482 patients mbtc assigned randomly ratio 7 3 investigational n 340 validation datasets n 142 continuous variables dichotomized using normal range best cutoff values determined using contal o quigley statistical methods following cox proportional hazard model scoring model derived summing rounded chi square scores factors identified multivariate analysis results performance status eastern cooperative oncology group 3 4 hypoalbuminemia 3 4 mg dl carcinoembryonic antigen 9 ng ml neutrophil lymphocyte ratio 3 0 carbohydrate antigen 19 9 120 u ml identified independent prognosticators harrell c index 0 682 integrated area curve 0 653 survival clearly correlated risk groups low intermediate high 14 0 7 3 2 3 months respectively p 0 001 prognosis also discriminative validation data set median survival 16 7 7 5 1 9 months respectively p 0 001 chemotherapy offer survival benefits high risk patients conclusion proposed prognostic criteria mbtc facilitate accurate patient risk stratification treatment related decision making pubmed","probabilities":0.9799733,"Title":"Prognostic Factors and Scoring Model for Survival in Metastatic Biliary Tract Cancer","Abstract":"PURPOSE: Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification. MATERIALS AND METHODS: From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox's proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis. RESULTS: The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell's C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients. CONCLUSION: These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Factors and Scoring Model for Survival in Metastatic Biliary Tract Cancer PURPOSE: Metastatic biliary tract cancer (mBTC) has a dismal prognosis. In this study, an independent dataset of patients with mBTC was used to implement and validate a routine clinico-laboratory parameter-based scoring model for risk group identification. MATERIALS AND METHODS: From September 2006 to February 2015, 482 patients with mBTC were assigned randomly (ratio, 7:3) into investigational (n=340) and validation datasets (n=142). The continuous variables were dichotomized using a normal range or the best cutoff values determined using the Contal and O'Quigley statistical methods. Following a Cox's proportional hazard model, the scoring model was derived by summing the rounded chi-square scores for the factors identified by multivariate analysis. RESULTS: The performance status (Eastern Cooperative Oncology Group 3-4), hypoalbuminemia (< 3.4 mg/dL), carcinoembryonic antigen (≥ 9 ng/mL), neutrophil-to-lymphocyte ratio (≥ 3.0), and carbohydrate antigen 19-9 (≥ 120 U/mL) were identified as independent prognosticators (Harrell's C index, 0.682; integrated area under the curve, 0.653). Survival was clearly correlated with the risk groups (low, intermediate, and high, 14.0, 7.3, and 2.3 months, respectively; p < 0.001). The prognosis was also discriminative in the validation data set (median survival, 16.7, 7.5, and 1.9 months, respectively; p < 0.001). Chemotherapy did not offer any survival benefits for high-risk patients. CONCLUSION: These proposed prognostic criteria for mBTC can facilitate accurate patient risk stratification and treatment-related decision-making. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value lymphovascular invasion bismuth corlette type iv hilar cholangiocarcinoma aim assess prognostic value lymphovascular invasion lvi bismuth corlette type iv hilar cholangiocarcinoma hc patients methods retrospective analysis performed 142 consecutively recruited type iv hc patients undergoing radical resection least 5 years follow survival analysis performed kaplan meier method association clinicopathologic variables survival evaluated log rank test multivariate analysis adopted identify independent prognostic factors overall survival os disease free survival dfs multiple logistic regression analysis performed determine association lvi potential variables results lvi confirmed histopathologically 29 20 4 patients multivariate analysis showed positive resection margin hr 6 255 95 ci 3 485 11 229 p 0 001 n1 stage hr 2 902 95 ci 1 132 7 439 p 0 027 tumor size 30 mm hr 1 942 95 ci 1 176 3 209 p 0 010 lvi positivity hr 2 799 95 ci 1 588 4 935 p 0 001 adverse prognostic factors dfs independent risk factors os positive resection margin hr 6 776 95 ci 3 988 11 479 p 0 001 n1 stage hr 2 827 95 ci 1 243 6 429 p 0 013 tumor size 30 mm hr 1 739 95 ci 1 101 2 745 p 0 018 lvi positivity hr 2 908 95 ci 1 712 4 938 p 0 001 lvi associated n1 stage tumor size 30 mm multiple logistic regression analysis indicated n1 stage hr 3 312 95 ci 1 338 8 198 p 0 026 tumor size 30 mm hr 3 258 95 ci 1 288 8 236 p 0 013 associated lvi conclusion lvi associated n1 stage tumor size 30 mm adversely influences dfs os type iv hc patients pubmed","probabilities":0.9799733,"Title":"Prognostic value of lymphovascular invasion in Bismuth-Corlette type IV hilar cholangiocarcinoma","Abstract":"AIM: To assess the prognostic value of lymphovascular invasion (LVI) in Bismuth-Corlette type IV hilar cholangiocarcinoma (HC) patients. METHODS: A retrospective analysis was performed on 142 consecutively recruited type IV HC patients undergoing radical resection with at least 5 years of follow-up. Survival analysis was performed by the Kaplan-Meier method, and the association between the clinicopathologic variables and survival was evaluated by log-rank test. Multivariate analysis was adopted to identify the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Multiple logistic regression analysis was performed to determine the association between LVI and potential variables. RESULTS: LVI was confirmed histopathologically in 29 (20.4%) patients. Multivariate analysis showed that positive resection margin (HR = 6.255, 95%CI: 3.485-11.229, P < 0.001), N1 stage (HR = 2.902, 95%CI: 1.132-7.439, P = 0.027), tumor size > 30 mm (HR = 1.942, 95%CI: 1.176-3.209, P = 0.010) and LVI positivity (HR = 2.799, 95%CI: 1.588-4.935, P < 0.001) were adverse prognostic factors for DFS. The independent risk factors for OS were positive resection margin (HR = 6.776, 95%CI: 3.988-11.479, P < 0.001), N1 stage (HR = 2.827, 95%CI: 1.243-6.429, P = 0.013), tumor size > 30 mm (HR = 1.739, 95%CI: 1.101-2.745, P = 0.018) and LVI positivity (HR = 2.908, 95%CI: 1.712-4.938, P < 0.001). LVI was associated with N1 stage and tumor size > 30 mm. Multiple logistic regression analysis indicated that N1 stage (HR = 3.312, 95%CI: 1.338-8.198, P = 0.026) and tumor size > 30 mm (HR = 3.258, 95%CI: 1.288-8.236, P = 0.013) were associated with LVI. CONCLUSION: LVI is associated with N1 stage and tumor size > 30 mm and adversely influences DFS and OS in type IV HC patients.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic value of lymphovascular invasion in Bismuth-Corlette type IV hilar cholangiocarcinoma AIM: To assess the prognostic value of lymphovascular invasion (LVI) in Bismuth-Corlette type IV hilar cholangiocarcinoma (HC) patients. METHODS: A retrospective analysis was performed on 142 consecutively recruited type IV HC patients undergoing radical resection with at least 5 years of follow-up. Survival analysis was performed by the Kaplan-Meier method, and the association between the clinicopathologic variables and survival was evaluated by log-rank test. Multivariate analysis was adopted to identify the independent prognostic factors for overall survival (OS) and disease-free survival (DFS). Multiple logistic regression analysis was performed to determine the association between LVI and potential variables. RESULTS: LVI was confirmed histopathologically in 29 (20.4%) patients. Multivariate analysis showed that positive resection margin (HR = 6.255, 95%CI: 3.485-11.229, P < 0.001), N1 stage (HR = 2.902, 95%CI: 1.132-7.439, P = 0.027), tumor size > 30 mm (HR = 1.942, 95%CI: 1.176-3.209, P = 0.010) and LVI positivity (HR = 2.799, 95%CI: 1.588-4.935, P < 0.001) were adverse prognostic factors for DFS. The independent risk factors for OS were positive resection margin (HR = 6.776, 95%CI: 3.988-11.479, P < 0.001), N1 stage (HR = 2.827, 95%CI: 1.243-6.429, P = 0.013), tumor size > 30 mm (HR = 1.739, 95%CI: 1.101-2.745, P = 0.018) and LVI positivity (HR = 2.908, 95%CI: 1.712-4.938, P < 0.001). LVI was associated with N1 stage and tumor size > 30 mm. Multiple logistic regression analysis indicated that N1 stage (HR = 3.312, 95%CI: 1.338-8.198, P = 0.026) and tumor size > 30 mm (HR = 3.258, 95%CI: 1.288-8.236, P = 0.013) were associated with LVI. CONCLUSION: LVI is associated with N1 stage and tumor size > 30 mm and adversely influences DFS and OS in type IV HC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"stage hilar cholangiocarcinoma predicts recurrence biliary obstruction patients metal stents background aims patients hilar cholangiocarcinomas present unresectable tumors palliative biliary drainage self expanding metal stents sems possible stents eventually cease function tumor overgrowth causes important identify factors affect stent patency failure examined patency endoscopically placed sems patients hilar cholangiocarcinoma factors associated patency methods performed retrospective study 120 consecutive patients mean age 67 14 6 years 74 male presented obstructive jaundice hilar cholangiocarcinoma underwent bilateral sems september 2006 april 2012 2 us tertiary medical centers collected data patient demographics survival success stent placement function immediate adverse events primary outcome duration stent patency time insertion failure results thirty eight patients stage 1 hilar cholangiocarcinomas 45 stage 2 12 stage 3 25 stage 4 median length hilar stricture 9 mm range 8 50 mm stent successfully passaged across stricture patients functional 115 median length 8 mm range 8 10 mm diameter 80 mm range 60 100 mm fourteen patients immediate adverse events including perforation n 2 bleeding n 2 pancreatitis n 9 cholangitis n 1 median survival 17 weeks range 1 211 weeks 50 patients stent occlusion kaplan meier analysis median time stent placement occlusion 17 weeks range 1 104 weeks patients stage 3 4 tumors 64 sems occlusion patients stage 1 2 tumors 28 univariate analysis p 017 multivariate analysis cancer stage independently significantly associated patency p 006 hazard ratio 2 77 age sex length stricture sems diameter length conclusions cumulative patency bilateral sems hilar cholangiocarcinoma significantly decreases tumor stage increases age sex length stricture sems diameter length associated sems patency pubmed","probabilities":0.9799733,"Title":"Stage of hilar cholangiocarcinoma predicts recurrence of biliary obstruction in patients with metal stents","Abstract":"BACKGROUND & AIMS: Most patients with hilar cholangiocarcinomas present with unresectable tumors, so only palliative biliary drainage with self-expanding metal stents (SEMS) is possible. Stents eventually cease to function because of tumor overgrowth and/or other causes, so it is important to identify factors that affect stent patency and failure. We examined the patency of endoscopically placed SEMS in patients with hilar cholangiocarcinoma and factors associated with patency. METHODS: We performed a retrospective study of 120 consecutive patients (mean age, 67 ± 14.6 years; 74 male) who presented with obstructive jaundice from hilar cholangiocarcinoma and underwent bilateral SEMS from September 2006 through April 2012 at 2 US tertiary medical centers. We collected data on patient demographics and survival, success of stent placement and function, and immediate adverse events. The primary outcome was duration of stent patency (time from insertion to failure). RESULTS: Thirty-eight patients had stage 1 hilar cholangiocarcinomas, 45 had stage 2, 12 had stage 3, and 25 had stage 4. The median length of the hilar stricture was 9 mm (range, 8-50 mm). The stent was successfully passaged across the stricture in all patients and was functional in 115; its median length was 8 mm (range, 8-10 mm), and diameter was 80 mm (range, 60-100 mm). Fourteen patients had immediate adverse events, including perforation (n = 2), bleeding (n = 2), pancreatitis (n = 9), and cholangitis (n = 1). Median survival was 17 weeks (range, 1-211 weeks), and 50 patients had stent occlusion. On Kaplan-Meier analysis, the median time from stent placement to occlusion was 17 weeks (range, 1-104 weeks). More patients with stage 3 or 4 tumors (64%) had SEMS occlusion than patients with stage 1 or 2 tumors (28%) in univariate analysis (P = .017). In multivariate analysis, only cancer stage was independently and significantly associated with patency (P = .006; hazard ratio, 2.77); age, sex, length of stricture, and SEMS diameter and length were not. CONCLUSIONS: The cumulative patency of bilateral SEMS for hilar cholangiocarcinoma significantly decreases as tumor stage increases. Age, sex, length of stricture, and SEMS diameter and length are not associated with SEMS patency.","Source":"PubMed","category":"HUMAN","training_data":"Stage of hilar cholangiocarcinoma predicts recurrence of biliary obstruction in patients with metal stents BACKGROUND & AIMS: Most patients with hilar cholangiocarcinomas present with unresectable tumors, so only palliative biliary drainage with self-expanding metal stents (SEMS) is possible. Stents eventually cease to function because of tumor overgrowth and/or other causes, so it is important to identify factors that affect stent patency and failure. We examined the patency of endoscopically placed SEMS in patients with hilar cholangiocarcinoma and factors associated with patency. METHODS: We performed a retrospective study of 120 consecutive patients (mean age, 67 ± 14.6 years; 74 male) who presented with obstructive jaundice from hilar cholangiocarcinoma and underwent bilateral SEMS from September 2006 through April 2012 at 2 US tertiary medical centers. We collected data on patient demographics and survival, success of stent placement and function, and immediate adverse events. The primary outcome was duration of stent patency (time from insertion to failure). RESULTS: Thirty-eight patients had stage 1 hilar cholangiocarcinomas, 45 had stage 2, 12 had stage 3, and 25 had stage 4. The median length of the hilar stricture was 9 mm (range, 8-50 mm). The stent was successfully passaged across the stricture in all patients and was functional in 115; its median length was 8 mm (range, 8-10 mm), and diameter was 80 mm (range, 60-100 mm). Fourteen patients had immediate adverse events, including perforation (n = 2), bleeding (n = 2), pancreatitis (n = 9), and cholangitis (n = 1). Median survival was 17 weeks (range, 1-211 weeks), and 50 patients had stent occlusion. On Kaplan-Meier analysis, the median time from stent placement to occlusion was 17 weeks (range, 1-104 weeks). More patients with stage 3 or 4 tumors (64%) had SEMS occlusion than patients with stage 1 or 2 tumors (28%) in univariate analysis (P = .017). In multivariate analysis, only cancer stage was independently and significantly associated with patency (P = .006; hazard ratio, 2.77); age, sex, length of stricture, and SEMS diameter and length were not. CONCLUSIONS: The cumulative patency of bilateral SEMS for hilar cholangiocarcinoma significantly decreases as tumor stage increases. Age, sex, length of stricture, and SEMS diameter and length are not associated with SEMS patency. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatitis viruses infection risk intrahepatic cholangiocarcinoma evidence meta analysis background studies investigating association hepatitis b virus hbv hepatitis c virus hcv infections intrahepatic cholangiocarcinoma icc reported inconsistent findings conducted meta analysis epidemiological studies explore relationship methods comprehensive search conducted identify eligible studies hepatitis infections icc risk september 2011 summary odds ratios 95 confidence intervals 95 ci calculated random effects models using review manager version 5 0 results thirteen case control studies 3 cohort studies included final analysis combined risk estimate studies showed statistically significant increased risk icc incidence hbv hcv infection 3 17 95 ci 1 88 5 34 3 42 95 ci 1 96 5 99 respectively case control studies alone combined infection hbv hcv 2 86 95 ci 1 60 5 11 3 63 95 ci 1 86 7 05 respectively cohort studies alone hbv hcv infection 5 39 95 ci 2 34 12 44 2 60 95 ci 1 36 4 97 respectively conclusions study suggests hbv hcv infection associated increased risk icc pubmed","probabilities":0.9799733,"Title":"Hepatitis viruses infection and risk of intrahepatic cholangiocarcinoma: evidence from a meta-analysis","Abstract":"BACKGROUND: Studies investigating the association between Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and intrahepatic cholangiocarcinoma (ICC) have reported inconsistent findings. We conducted a meta-analysis of epidemiological studies to explore this relationship. METHODS: A comprehensive search was conducted to identify the eligible studies of hepatitis infections and ICC risk up to September 2011. Summary odds ratios (OR) with their 95% confidence intervals (95% CI) were calculated with random-effects models using Review Manager version 5.0. RESULTS: Thirteen case-control studies and 3 cohort studies were included in the final analysis. The combined risk estimate of all studies showed statistically significant increased risk of ICC incidence with HBV and HCV infection (OR = 3.17, 95% CI, 1.88-5.34, and OR = 3.42, 95% CI, 1.96-5.99, respectively). For case-control studies alone, the combined OR of infection with HBV and HCV were 2.86 (95% CI, 1.60-5.11) and 3.63 (95% CI, 1.86-7.05), respectively, and for cohort studies alone, the OR of HBV and HCV infection were 5.39 (95% CI, 2.34-12.44) and 2.60 (95% CI, 1.36-4.97), respectively. CONCLUSIONS: This study suggests that both HBV and HCV infection are associated with an increased risk of ICC.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis viruses infection and risk of intrahepatic cholangiocarcinoma: evidence from a meta-analysis BACKGROUND: Studies investigating the association between Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections and intrahepatic cholangiocarcinoma (ICC) have reported inconsistent findings. We conducted a meta-analysis of epidemiological studies to explore this relationship. METHODS: A comprehensive search was conducted to identify the eligible studies of hepatitis infections and ICC risk up to September 2011. Summary odds ratios (OR) with their 95% confidence intervals (95% CI) were calculated with random-effects models using Review Manager version 5.0. RESULTS: Thirteen case-control studies and 3 cohort studies were included in the final analysis. The combined risk estimate of all studies showed statistically significant increased risk of ICC incidence with HBV and HCV infection (OR = 3.17, 95% CI, 1.88-5.34, and OR = 3.42, 95% CI, 1.96-5.99, respectively). For case-control studies alone, the combined OR of infection with HBV and HCV were 2.86 (95% CI, 1.60-5.11) and 3.63 (95% CI, 1.86-7.05), respectively, and for cohort studies alone, the OR of HBV and HCV infection were 5.39 (95% CI, 2.34-12.44) and 2.60 (95% CI, 1.36-4.97), respectively. CONCLUSIONS: This study suggests that both HBV and HCV infection are associated with an increased risk of ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"residual carcinoma situ ductal stump negative survival effect analysis early stage cholangiocarcinomas objective aim study evaluate whether carcinoma situ cis residue ductal stump affects survival patients undergoing resection extrahepatic cholangiocarcinoma background positive ductal margin cis treated tumor free margin prognostic viewpoint several studies reported residual cis foci ductal stump affect survival resection methods patients underwent resection extrahepatic cholangiocarcinoma retrospectively reviewed surgical margin status histologically divided negative r0 positive cis r1cis positive invasive cancer r1inv survival incidence local recurrence compared among groups results 684 consecutive resected patients 172 patients early stage ptis 2n0m0 cholangiocarcinoma perihilar n 144 distal n 28 analyzed cumulative incidence local recurrence r1cis patients higher r0 patients 32 8 vs 4 4 5 years p 0 001 lower r1inv patients 50 0 2 years p 0 012 disease specific survival r1cis patients worse r0 patients 35 1 vs 78 7 5 years p 0 005 better r1inv patients 40 0 2 years p 0 002 uni multivariate analyses identified surgical margin status independent prognostic factor r1cis vs r0 relative risk 2 39 p 0 026 r1inv vs r0 rr 10 28 p 0 001 conclusion r1cis increases incidence local recurrence shortens postoperative survival patients early stage cholangiocarcinoma although prognostic effect less severe compared r1inv r1cis avoided much possible surgery early stage cancer although may allowed advanced tumors stn","probabilities":0.9799733,"Title":"Residual Carcinoma In Situ At The Ductal Stump Has A Negative Survival Effect: An Analysis Of Early-Stage Cholangiocarcinomas","Abstract":"Objective: The aim of the study was to evaluate whether carcinoma in situ (CIS) residue at the ductal stump affects the survival of patients undergoing resection for extrahepatic cholangiocarcinoma. \r\n\r\n Background: Positive ductal margin with CIS has been treated as a tumor-free margin from a prognostic viewpoint because several studies have reported that residual CIS foci at the ductal stump do not affect survival after resection. \r\n\r\n Methods: Patients who underwent resection for extrahepatic cholangiocarcinoma were retrospectively reviewed. The surgical margin status was histologically divided into negative (R0), positive with CIS (R1cis), and positive with invasive cancer (R1inv). The survival and incidence of local recurrence were compared among the groups. \r\n\r\n Results: Of 684 consecutive resected patients, 172 patients with early-stage (pTis-2N0M0) cholangiocarcinoma (perihilar, n = 144; distal, n = 28) were analyzed. The cumulative incidence of local recurrence in R1cis patients was higher than R0 patients (32.8% vs 4.4% at 5 years, P < 0.001) and lower than R1inv patients (50.0% at 2 years, P = 0.012). The disease-specific survival for R1cis patients was worse than for R0 patients (35.1% vs 78.7% at 5 years, P = 0.005) and better than for R1inv patients (40.0% at 2 years, P = 0.002). The uni- and multivariate analyses identified the surgical margin status as an independent prognostic factor (R1cis vs R0, relative risk 2.39, P = 0.026; R1inv vs R0, RR 10.28, P < 0.001). \r\n\r\n Conclusion: R1cis increases the incidence of local recurrence and shortens postoperative survival in patients with early-stage cholangiocarcinoma, although this prognostic effect was less severe compared with R1inv. R1cis should be avoided as much as possible in surgery for early-stage cancer, although it may be allowed in advanced tumors.","Source":"STN","category":"HUMAN","training_data":"Residual Carcinoma In Situ At The Ductal Stump Has A Negative Survival Effect: An Analysis Of Early-Stage Cholangiocarcinomas Objective: The aim of the study was to evaluate whether carcinoma in situ (CIS) residue at the ductal stump affects the survival of patients undergoing resection for extrahepatic cholangiocarcinoma. \r\n\r\n Background: Positive ductal margin with CIS has been treated as a tumor-free margin from a prognostic viewpoint because several studies have reported that residual CIS foci at the ductal stump do not affect survival after resection. \r\n\r\n Methods: Patients who underwent resection for extrahepatic cholangiocarcinoma were retrospectively reviewed. The surgical margin status was histologically divided into negative (R0), positive with CIS (R1cis), and positive with invasive cancer (R1inv). The survival and incidence of local recurrence were compared among the groups. \r\n\r\n Results: Of 684 consecutive resected patients, 172 patients with early-stage (pTis-2N0M0) cholangiocarcinoma (perihilar, n = 144; distal, n = 28) were analyzed. The cumulative incidence of local recurrence in R1cis patients was higher than R0 patients (32.8% vs 4.4% at 5 years, P < 0.001) and lower than R1inv patients (50.0% at 2 years, P = 0.012). The disease-specific survival for R1cis patients was worse than for R0 patients (35.1% vs 78.7% at 5 years, P = 0.005) and better than for R1inv patients (40.0% at 2 years, P = 0.002). The uni- and multivariate analyses identified the surgical margin status as an independent prognostic factor (R1cis vs R0, relative risk 2.39, P = 0.026; R1inv vs R0, RR 10.28, P < 0.001). \r\n\r\n Conclusion: R1cis increases the incidence of local recurrence and shortens postoperative survival in patients with early-stage cholangiocarcinoma, although this prognostic effect was less severe compared with R1inv. R1cis should be avoided as much as possible in surgery for early-stage cancer, although it may be allowed in advanced tumors. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors curative treatment gallbladder cancer data 950 cases german registry background cases immediate radical re resection irr simple cholecystectomy incidental gallbladder carcinoma igbc needed s3 guidelines valid till 2015 recommended irr t2 advanced stages new s3 guidelines recommend aggressive surgery even t1b due german registry gr data according data gr indication irr depends experience hospitals liver surgery complying guidelines igbc patients staged incorrectly treated oncological sufficient practice following questions interest depends treatment igbc surgical oncological expertise clinics technique liver resection lr meaningful stage important regarding lymph node ratio lnr multimodal aspects methods data analysis used gr gr includes 1000 cases igbc largest gbc registry europe results date 950 cases igbc gr analyzed 42 113 t1b cases irr significant survival benefit t1b irr also significant survival benefit 228 t2 80 t3 irr 461 t2 215 t3 tumors comparison lr showed good results wedge resection technique wrt t1b t2 t3 radical techniques showed better results less 50 t2 3 tumors registry re resected lr performed significantly often high volume hv clinics 212 patients lnr calculated statistic showed lnr significant prognostic factor results show referral patients lv hv practical relevance conclusions igbc t1b needs radical surgery wrt attractive procedure t1b t2 igbc due lower invasiveness implantation also possible lv experience liver surgery also count retrieved lymph nodes essential interest following correct decision processes patients possibility cure increasing cure rate t2 3 gbc patients multimodal therapy trial planned investigator supported 300 clinics google scholar","probabilities":0.9799733,"Title":"Prognostic Factors In Curative Treatment Of Gallbladder Cancer-Data Of 950 Cases Of The German-Registry","Abstract":"Background\nIn most cases an immediate radical re-resection (IRR) after simple cholecystectomy in incidental gallbladder carcinoma (IGBC) is needed. The S3 guidelines valid till 2015 have recommended IRR in T2 and more advanced stages. The new S3- guidelines will recommend more aggressive surgery even in T1b, due to German- Registry (GR) data. According to the data of the GR the indication for IRR depends more on the experience of the hospitals in liver surgery than on complying with the guidelines, so most of IGBC- patients are staged incorrectly and not treated oncological sufficient. In practice, the following questions are of interest. Depends treatment of IGBC on the surgical or oncological expertise of the clinics? Which technique of liver resection (LR) is meaningful in which stage? What is important regarding lymph node ratio (LNR). What's about multimodal aspects.\nMethods\nFor data analysis we used the GR. The GR includes more than 1000 cases of IGBC and is the largest gbc registry in Europe.\nResults\nTo date more than 950 cases of IGBC in the GR have been analyzed. In 42 of 113 T1b cases there was an IRR, with a significant survival benefit for T1b after IRR. There was also a significant survival benefit for the 228 T2 and 80 T3 with IRR of the 461 T2 and 215 T3 tumors. Comparison of LR showed good results for the wedge resection technique (WRT) in T1b and T2. For T3 more radical techniques showed better results. Less than 50% of T2–3 tumors in the registry have been re-resected. LR was performed significantly more often in High- volume (HV) clinics. In 212 patients the LNR could be calculated. Statistic showed that LNR is a significant prognostic factor. The results show that the referral of patients from a LV to a HV has no practical relevance.\nConclusions\nIGBC's up to T1b needs radical surgery. WRT is an attractive procedure for T1b / T2 IGBC due to the lower invasiveness and implantation should also be possible in LV's with few experience in liver surgery. Also the count of retrieved lymph nodes is of essential interest. By following the correct decision processes more patients have the possibility for cure. For further increasing the cure rate in T2-3 GBC patients a multimodal therapy trial has been planned by the investigator supported by of more than 300 clinics.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Factors In Curative Treatment Of Gallbladder Cancer-Data Of 950 Cases Of The German-Registry Background\nIn most cases an immediate radical re-resection (IRR) after simple cholecystectomy in incidental gallbladder carcinoma (IGBC) is needed. The S3 guidelines valid till 2015 have recommended IRR in T2 and more advanced stages. The new S3- guidelines will recommend more aggressive surgery even in T1b, due to German- Registry (GR) data. According to the data of the GR the indication for IRR depends more on the experience of the hospitals in liver surgery than on complying with the guidelines, so most of IGBC- patients are staged incorrectly and not treated oncological sufficient. In practice, the following questions are of interest. Depends treatment of IGBC on the surgical or oncological expertise of the clinics? Which technique of liver resection (LR) is meaningful in which stage? What is important regarding lymph node ratio (LNR). What's about multimodal aspects.\nMethods\nFor data analysis we used the GR. The GR includes more than 1000 cases of IGBC and is the largest gbc registry in Europe.\nResults\nTo date more than 950 cases of IGBC in the GR have been analyzed. In 42 of 113 T1b cases there was an IRR, with a significant survival benefit for T1b after IRR. There was also a significant survival benefit for the 228 T2 and 80 T3 with IRR of the 461 T2 and 215 T3 tumors. Comparison of LR showed good results for the wedge resection technique (WRT) in T1b and T2. For T3 more radical techniques showed better results. Less than 50% of T2–3 tumors in the registry have been re-resected. LR was performed significantly more often in High- volume (HV) clinics. In 212 patients the LNR could be calculated. Statistic showed that LNR is a significant prognostic factor. The results show that the referral of patients from a LV to a HV has no practical relevance.\nConclusions\nIGBC's up to T1b needs radical surgery. WRT is an attractive procedure for T1b / T2 IGBC due to the lower invasiveness and implantation should also be possible in LV's with few experience in liver surgery. Also the count of retrieved lymph nodes is of essential interest. By following the correct decision processes more patients have the possibility for cure. For further increasing the cure rate in T2-3 GBC patients a multimodal therapy trial has been planned by the investigator supported by of more than 300 clinics.\n Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"aberrant methylation htatip2 uchl1 predictive biomarker cholangiocarcinoma cholangiocarcinoma cca common primary liver cancer northeastern thailand liver fluke infection highly endemic although aberrant dna methylation cca reported several investigators little known regarding associations present study results obtained previously published methylation array analyzed 10 candidate genes involved dna repair protein phosphatase 4 catalytic subunit ppp4c apoptosis runt related transcription factor 3 runx3 interferon regulatory factor 4 irf4 ubiquitin c terminal hydrolase l1 uchl1 tumor protein p53 inducible protein 3 tp53i3 cell proliferation cyclin d2 ccnd2 ras association domain family member 1 rassf1 drug metabolism aldehyde dehydrogenase 1 family member a3 aldh1a3 solute carrier family 29 member 1 slc29a1 angiogenesis human immunodeficiency virus 1 tat interactive protein 2 htatip2 selected quantification methylation levels 54 cca 19 adjacent normal tissues using methylation sensitive high resolution melting associations methylation status individual genes clinical parameters statistically analyzed high methylation levels observed uchl1 irf4 ccnd2 htatip2 tp53i3 median methylation level uchl1 57 3 range 3 15 88 7 htatip2 13 6 range 7 5 36 7 contrast low methylation htatip2 uchl1 identified adjacent normal tissues methylation status htatip2 uchl1 associated patients overall survival cca patients high methylation htatip2 low methylation uchl1 exhibited longer overall survival addition multivariate cox regression analysis demonstrated uchl1 methylation independent factor cca hazard ratio 1 81 95 confidence interval 1 01 3 25 high methylation group combination htatip2 uchl1 methylation status strongly supported potential predictive biomarker patients cca high methylation htatip2 low methylation uchl1 showed longer overall survival low htatip2 methylation high uchl1 methylation conclusion present study revealed value aberrant dna methylation htatip2 uchl1 may serve potential predictive biomarker cca stn","probabilities":0.9467213,"Title":"Aberrant Methylation Of Htatip2 And Uchl1 As A Predictive Biomarker For Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is the most common primary liver cancer in Northeastern Thailand where liver fluke infection is highly endemic. Although aberrant DNA methylation in CCA has been reported by several investigators, little is known regarding the associations between them. In the present study, the results obtained from our previously published methylation array were analyzed and 10 candidate genes involved in DNA repair [protein phosphatase 4 catalytic subunit (PPP4C)], apoptosis [runt related transcription factor 3 (RUNX3), interferon regulatory factor 4 (IRF4), ubiquitin C‑terminal hydrolase L1 (UCHL1) and tumor protein p53 inducible protein 3 (TP53I3)], cell proliferation [cyclin D2 (CCND2) and Ras association domain family member 1 (RASSF1)], drug metabolism [aldehyde dehydrogenase 1 family member A3 (ALDH1A3) and solute carrier family 29 member 1 (SLC29A1)] and angiogenesis [human immunodeficiency virus‑1 tat interactive protein 2 (HTATIP2)] were selected for quantification of their methylation levels in 54 CCA and 19 adjacent normal tissues using methylation‑sensitive high‑resolution melting. The associations between the methylation status of the individual genes and clinical parameters were statistically analyzed. High methylation levels were observed in UCHL1, IRF4, CCND2, HTATIP2 and TP53I3. The median methylation level of UCHL1 was 57.3% (range, 3.15 to 88.7%) and HTATIP2 was 13.6% (range, 7.5 to 36.7%). By contrast, low methylation of HTATIP2 and UCHL1 was identified in adjacent normal tissues. The methylation status of HTATIP2 and UCHL1 was associated with patients' overall survival. CCA patients with high methylation of HTATIP2 and low methylation of UCHL1 exhibited longer overall survival. In addition, multivariate Cox regression analysis demonstrated that UCHL1 methylation was an independent factor for CCA with hazard ratio of 1.81 (95% confidence interval, 1.01‑3.25) in high methylation group. The combination of HTATIP2 and UCHL1 methylation status strongly supported their potential predictive biomarker in which patients with CCA who had high methylation of HTATIP2 and low methylation of UCHL1 showed longer overall survival than those with low HTATIP2 methylation and high UCHL1 methylation. In conclusion, the present study revealed the value of aberrant DNA methylation of HTATIP2 and UCHL1, which may serve as a potential predictive biomarker for CCA.","Source":"STN","category":"ANIMAL","training_data":"Aberrant Methylation Of Htatip2 And Uchl1 As A Predictive Biomarker For Cholangiocarcinoma Cholangiocarcinoma (CCA) is the most common primary liver cancer in Northeastern Thailand where liver fluke infection is highly endemic. Although aberrant DNA methylation in CCA has been reported by several investigators, little is known regarding the associations between them. In the present study, the results obtained from our previously published methylation array were analyzed and 10 candidate genes involved in DNA repair [protein phosphatase 4 catalytic subunit (PPP4C)], apoptosis [runt related transcription factor 3 (RUNX3), interferon regulatory factor 4 (IRF4), ubiquitin C‑terminal hydrolase L1 (UCHL1) and tumor protein p53 inducible protein 3 (TP53I3)], cell proliferation [cyclin D2 (CCND2) and Ras association domain family member 1 (RASSF1)], drug metabolism [aldehyde dehydrogenase 1 family member A3 (ALDH1A3) and solute carrier family 29 member 1 (SLC29A1)] and angiogenesis [human immunodeficiency virus‑1 tat interactive protein 2 (HTATIP2)] were selected for quantification of their methylation levels in 54 CCA and 19 adjacent normal tissues using methylation‑sensitive high‑resolution melting. The associations between the methylation status of the individual genes and clinical parameters were statistically analyzed. High methylation levels were observed in UCHL1, IRF4, CCND2, HTATIP2 and TP53I3. The median methylation level of UCHL1 was 57.3% (range, 3.15 to 88.7%) and HTATIP2 was 13.6% (range, 7.5 to 36.7%). By contrast, low methylation of HTATIP2 and UCHL1 was identified in adjacent normal tissues. The methylation status of HTATIP2 and UCHL1 was associated with patients' overall survival. CCA patients with high methylation of HTATIP2 and low methylation of UCHL1 exhibited longer overall survival. In addition, multivariate Cox regression analysis demonstrated that UCHL1 methylation was an independent factor for CCA with hazard ratio of 1.81 (95% confidence interval, 1.01‑3.25) in high methylation group. The combination of HTATIP2 and UCHL1 methylation status strongly supported their potential predictive biomarker in which patients with CCA who had high methylation of HTATIP2 and low methylation of UCHL1 showed longer overall survival than those with low HTATIP2 methylation and high UCHL1 methylation. In conclusion, the present study revealed the value of aberrant DNA methylation of HTATIP2 and UCHL1, which may serve as a potential predictive biomarker for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"intrahepatic perihilar distal cholangiocarcinoma management outcomes introduction aims cholangiocarcinomas heterogeneous group tumors classified three clinically distinct types cancers intrahepatic perihilar distal cholangiocarcinoma inconsistent use nomenclature cancers obscured true knowledge epidemiology natural history response therapy cancers aims define demographic characteristics management outcomes three distinct cancer types materials methods retrospective study patients enrolled institutional cancer registry 1992 2010 median survival compared different treatment modalities three time periods three types cholangiocarcinoma different stages disease using kaplan meyer analysis results 242 patients identified cases reviewed classified intrahepatic 90 patients distal 48 patients perihilar 104 patients cholangiocarcinomas cancers differed median age onset gender distribution median survival stage 13 8 patients presented stage 5 8 stage ii 9 6 stage iii 28 stage iv 41 8 unknown stage overall median survival 15 8 months 23 25 14 4 5 months stages ii iii iv respectively surgery improved survival early advanced stages multimodality therapies improved outcomes particularly perihilar cholangiocarcinoma conclusion perihilar distal intrahepatic cholangiocarcinoma vary presentation natural history therapeutic approach management consistently applied classification essential meaningful interpretation studies cancers pubmed","probabilities":0.9799733,"Title":"Intrahepatic, perihilar and distal cholangiocarcinoma: Management and outcomes","Abstract":"Introduction and aims. Cholangiocarcinomas are a heterogeneous group of tumors that can be classified into three clinically distinct types of cancers, intrahepatic, perihilar and distal cholangiocarcinoma. The inconsistent use of nomenclature for these cancers has obscured a true knowledge of the epidemiology, natural history and response to therapy of these cancers. Our aims were to define demographic characteristics, management and outcomes of these three distinct cancer types. MATERIALS AND METHODS: A retrospective study of patients enrolled in an institutional cancer registry from 1992 to 2010. Median survival was compared between different treatment modalities over three time periods for the three types of cholangiocarcinoma at different stages of the disease using Kaplan Meyer analysis. RESULTS: 242 patients were identified. All cases were reviewed and classified into intrahepatic (90 patients), distal (48 patients) or perihilar (104 patients) cholangiocarcinomas. These cancers differed in median age of onset, gender distribution, median survival and stage. 13.8% of patients presented with stage I, 5.8% with stage II, 9.6% with stage III, 28% with stage IV, with 41.8% having unknown stage. The overall median survival was 15.8 months, and was 23, 25, 14, and 4.5 months for stages I, II, III, and IV respectively. Surgery improved survival in both early and advanced stages. Multimodality therapies further improved outcomes, particularly for perihilar cholangiocarcinoma. CONCLUSION: Perihilar, distal and intrahepatic cholangiocarcinoma vary in their presentation, natural history and therapeutic approach to management. A consistently applied classification is essential for meaningful interpretation of studies of these cancers.","Source":"PubMed","category":"HUMAN","training_data":"Intrahepatic, perihilar and distal cholangiocarcinoma: Management and outcomes Introduction and aims. Cholangiocarcinomas are a heterogeneous group of tumors that can be classified into three clinically distinct types of cancers, intrahepatic, perihilar and distal cholangiocarcinoma. The inconsistent use of nomenclature for these cancers has obscured a true knowledge of the epidemiology, natural history and response to therapy of these cancers. Our aims were to define demographic characteristics, management and outcomes of these three distinct cancer types. MATERIALS AND METHODS: A retrospective study of patients enrolled in an institutional cancer registry from 1992 to 2010. Median survival was compared between different treatment modalities over three time periods for the three types of cholangiocarcinoma at different stages of the disease using Kaplan Meyer analysis. RESULTS: 242 patients were identified. All cases were reviewed and classified into intrahepatic (90 patients), distal (48 patients) or perihilar (104 patients) cholangiocarcinomas. These cancers differed in median age of onset, gender distribution, median survival and stage. 13.8% of patients presented with stage I, 5.8% with stage II, 9.6% with stage III, 28% with stage IV, with 41.8% having unknown stage. The overall median survival was 15.8 months, and was 23, 25, 14, and 4.5 months for stages I, II, III, and IV respectively. Surgery improved survival in both early and advanced stages. Multimodality therapies further improved outcomes, particularly for perihilar cholangiocarcinoma. CONCLUSION: Perihilar, distal and intrahepatic cholangiocarcinoma vary in their presentation, natural history and therapeutic approach to management. A consistently applied classification is essential for meaningful interpretation of studies of these cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"choledochal cyst malignancy plea lifelong follow previous research confirmed patients choledochal cyst elevated risk cholangiocarcinoma gallbladder carcinoma current data suggest risk malignancy 6 30 adults choledochal cyst malignancy also occasionally identified children adolescents multiple factors including age patient cyst type histological findings localization impact prognosis information long term outcomes cyst excision limited however recent data suggest lifelong elevated risk 4 cancer development following operation paper presents review literature cancer patients choledochal cyst excision postoperative follow concept consists annual controls ca19 9 abdominal ultrasound introduced pubmed","probabilities":0.9799733,"Title":"Choledochal Cyst and Malignancy: A Plea for Lifelong Follow-Up","Abstract":"Previous research has confirmed that patients with choledochal cyst have an elevated risk of cholangiocarcinoma and gallbladder carcinoma. Current data suggest a risk of malignancy of 6 to 30% in adults with choledochal cyst. Malignancy has also occasionally been identified in children and adolescents. Multiple factors, including the age of the patient, cyst type, histological findings, and localization, have an impact on the prognosis. Information on long-term outcomes after cyst excision is limited. However, recent data suggest a lifelong elevated risk of up to 4% of cancer development following operation. This paper presents a review of the literature on cancer in patients with choledochal cyst before and after excision. A postoperative follow-up concept that consists of annual controls of CA19-9 and abdominal ultrasound is introduced.","Source":"PubMed","category":"HUMAN","training_data":"Choledochal Cyst and Malignancy: A Plea for Lifelong Follow-Up Previous research has confirmed that patients with choledochal cyst have an elevated risk of cholangiocarcinoma and gallbladder carcinoma. Current data suggest a risk of malignancy of 6 to 30% in adults with choledochal cyst. Malignancy has also occasionally been identified in children and adolescents. Multiple factors, including the age of the patient, cyst type, histological findings, and localization, have an impact on the prognosis. Information on long-term outcomes after cyst excision is limited. However, recent data suggest a lifelong elevated risk of up to 4% of cancer development following operation. This paper presents a review of the literature on cancer in patients with choledochal cyst before and after excision. A postoperative follow-up concept that consists of annual controls of CA19-9 and abdominal ultrasound is introduced. PubMed","prediction_labels":"HUMAN"},{"cleaned":"modern perspectives factors predisposing development gallbladder cancer background gallbladder cancer gbc rare malignancy yet certain groups higher risk knowledge predisposing factors may facilitate earlier diagnosis enabling targeted investigations otherwise non specific presenting signs symptoms detecting gbc initial stages offers patients best chance cure methods pubmed searched recent articles 2008 2012 topic risk factors gbc 1490 initial entries 32 manuscripts reporting risk factors gbc included review results new molecular perspectives cholesterol cycling hormonal factors bacterial infection provide fresh insights established risk factors gallstones female gender geographic locality significance polyps predisposing gbc probably overstated given known dysplasia carcinoma adenoma carcinoma sequences active disease bacteria salmonella species may contribute regional variations disease prevalence might represent powerful targets therapy reduce incidences high risk areas traditional risk factors porcelain gallbladder mirizzi syndrome bile reflux remain important predisposing factors conclusions subcentimetre gallbladder polyps rarely become cancerous gallbladder wall thickening often first sign malignancy gallbladder imaging scrutinized carefully feature pubmed","probabilities":0.9799733,"Title":"Modern perspectives on factors predisposing to the development of gallbladder cancer","Abstract":"BACKGROUND: Gallbladder cancer (GBC) is a rare malignancy, yet certain groups are at higher risk. Knowledge of predisposing factors may facilitate earlier diagnosis by enabling targeted investigations into otherwise non-specific presenting signs and symptoms. Detecting GBC in its initial stages offers patients their best chance of cure. METHODS: PubMed was searched for recent articles (2008-2012) on the topic of risk factors for GBC. Of 1490 initial entries, 32 manuscripts reporting on risk factors for GBC were included in this review. RESULTS: New molecular perspectives on cholesterol cycling, hormonal factors and bacterial infection provide fresh insights into the established risk factors of gallstones, female gender and geographic locality. The significance of polyps in predisposing to GBC is probably overstated given the known dysplasia-carcinoma and adenoma-carcinoma sequences active in this disease. Bacteria such as Salmonella species may contribute to regional variations in disease prevalence and might represent powerful targets of therapy to reduce incidences in high-risk areas. Traditional risk factors such as porcelain gallbladder, Mirizzi's syndrome and bile reflux remain important as predisposing factors. CONCLUSIONS: Subcentimetre gallbladder polyps rarely become cancerous. Because gallbladder wall thickening is often the first sign of malignancy, all gallbladder imaging should be scrutinized carefully for this feature.","Source":"PubMed","category":"HUMAN","training_data":"Modern perspectives on factors predisposing to the development of gallbladder cancer BACKGROUND: Gallbladder cancer (GBC) is a rare malignancy, yet certain groups are at higher risk. Knowledge of predisposing factors may facilitate earlier diagnosis by enabling targeted investigations into otherwise non-specific presenting signs and symptoms. Detecting GBC in its initial stages offers patients their best chance of cure. METHODS: PubMed was searched for recent articles (2008-2012) on the topic of risk factors for GBC. Of 1490 initial entries, 32 manuscripts reporting on risk factors for GBC were included in this review. RESULTS: New molecular perspectives on cholesterol cycling, hormonal factors and bacterial infection provide fresh insights into the established risk factors of gallstones, female gender and geographic locality. The significance of polyps in predisposing to GBC is probably overstated given the known dysplasia-carcinoma and adenoma-carcinoma sequences active in this disease. Bacteria such as Salmonella species may contribute to regional variations in disease prevalence and might represent powerful targets of therapy to reduce incidences in high-risk areas. Traditional risk factors such as porcelain gallbladder, Mirizzi's syndrome and bile reflux remain important as predisposing factors. CONCLUSIONS: Subcentimetre gallbladder polyps rarely become cancerous. Because gallbladder wall thickening is often the first sign of malignancy, all gallbladder imaging should be scrutinized carefully for this feature. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incretin based drugs risk cholangiocarcinoma among patients type 2 diabetes objective determine whether use dipeptidyl peptidase 4 dpp 4 inhibitors glucagon like peptide 1 glp 1 receptor agonists associated increased risk cholangiocarcinoma adults type 2 diabetes design population based cohort study setting general practices contributing data uk clinical practice research datalink participants 154 162 adults newly treated antidiabetic drugs 1 january 2007 31 march 2017 followed 31 march 2018 main outcome measures use dpp 4 inhibitors glp 1 receptor agonists modelled time varying variable compared use second third line antidiabetic drugs exposures lagged one year account cancer latency minimise reverse causality cox proportional hazards models used estimate hazard ratios 95 confidence intervals incident cholangiocarcinoma associated use dpp 4 inhibitors glp 1 receptor agonists separately post hoc pharmacovigilance analysis conducted using world health organization global individual case safety report database vigibase estimate reporting odds ratios cholangiocarcinoma results 614 274 person years follow 105 incident cholangiocarcinoma events occurred rate 17 1 per 100 000 person years use dpp 4 inhibitors associated 77 increased hazard cholangiocarcinoma hazard ratio 1 77 95 confidence interval 1 04 3 01 use glp 1 receptor agonists associated increased hazard wide confidence interval hazard ratio 1 97 0 83 4 66 pharmacovigilance analysis use dpp 4 inhibitors glp 1 receptor agonists associated increased reporting odds ratios cholangiocarcinoma compared use sulfonylureas thiazolidinediones 1 63 1 00 2 66 4 73 2 95 7 58 respectively conclusion compared use second third line antidiabetic drugs use dpp 4 inhibitors possibly glp 1 receptor agonists might associated increased risk cholangiocarcinoma adults type 2 diabetes stn","probabilities":0.9799733,"Title":"Incretin-Based Drugs And The Risk Of Cholangiocarcinoma Among Patients With Type 2 Diabetes","Abstract":"Objective: To determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. \r\n\r\n Design: Population based cohort study. \r\n\r\n Setting: General practices contributing data to the UK Clinical Practice Research Datalink. \r\n\r\n Participants: 154 162 adults newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2017, followed until 31 March 2018. \r\n\r\n Main outcome measures: Use of DPP-4 inhibitors and GLP-1 receptor agonists was modelled as a time varying variable and compared with use of other second or third line antidiabetic drugs. All exposures were lagged by one year to account for cancer latency and to minimise reverse causality. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of incident cholangiocarcinoma associated with use of DPP-4 inhibitors and GLP-1 receptor agonists, separately. A post hoc pharmacovigilance analysis was conducted using the World Health Organization's global individual case safety report database, VigiBase, to estimate reporting odds ratios of cholangiocarcinoma. \r\n\r\n Results: During 614 274 person years of follow-up, 105 incident cholangiocarcinoma events occurred (rate 17.1 per 100 000 person years). Use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma (hazard ratio 1.77, 95% confidence interval 1.04 to 3.01). Use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval (hazard ratio 1.97, 0.83 to 4.66). In the pharmacovigilance analysis, the use of DPP-4 inhibitors and GLP-1 receptor agonists were both associated with increased reporting odds ratios for cholangiocarcinoma, compared with use of sulfonylureas or thiazolidinediones (1.63, 1.00 to 2.66, 4.73, 2.95 to 7.58, respectively). \r\n\r\n Conclusion: Compared with use of other second or third line antidiabetic drugs, use of DPP-4 inhibitors, and possibly GLP-1 receptor agonists, might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes.","Source":"STN","category":"HUMAN","training_data":"Incretin-Based Drugs And The Risk Of Cholangiocarcinoma Among Patients With Type 2 Diabetes Objective: To determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. \r\n\r\n Design: Population based cohort study. \r\n\r\n Setting: General practices contributing data to the UK Clinical Practice Research Datalink. \r\n\r\n Participants: 154 162 adults newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2017, followed until 31 March 2018. \r\n\r\n Main outcome measures: Use of DPP-4 inhibitors and GLP-1 receptor agonists was modelled as a time varying variable and compared with use of other second or third line antidiabetic drugs. All exposures were lagged by one year to account for cancer latency and to minimise reverse causality. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of incident cholangiocarcinoma associated with use of DPP-4 inhibitors and GLP-1 receptor agonists, separately. A post hoc pharmacovigilance analysis was conducted using the World Health Organization's global individual case safety report database, VigiBase, to estimate reporting odds ratios of cholangiocarcinoma. \r\n\r\n Results: During 614 274 person years of follow-up, 105 incident cholangiocarcinoma events occurred (rate 17.1 per 100 000 person years). Use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma (hazard ratio 1.77, 95% confidence interval 1.04 to 3.01). Use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval (hazard ratio 1.97, 0.83 to 4.66). In the pharmacovigilance analysis, the use of DPP-4 inhibitors and GLP-1 receptor agonists were both associated with increased reporting odds ratios for cholangiocarcinoma, compared with use of sulfonylureas or thiazolidinediones (1.63, 1.00 to 2.66, 4.73, 2.95 to 7.58, respectively). \r\n\r\n Conclusion: Compared with use of other second or third line antidiabetic drugs, use of DPP-4 inhibitors, and possibly GLP-1 receptor agonists, might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. STN","prediction_labels":"HUMAN"},{"cleaned":"17 years retrospective study multiple metal stents complex malignant hilar biliary strictures survival stents patency outcomes re interventions occluded metal stents background endoscopic placement semss malignant hilar biliary strictures mhbs well established palliative treatment inoperable patients objectives study evaluation survival stents patency placement multiple sems palliation complex mhbs methods retrospective review patients mhbs underwent ercp insertion multiple semss palliation survival associated factors stents patency analyzed cox multivariate analysis results january 1998 january 2015 740 patients nonoperable mhbs underwent ercp identified 18 2 received multiple semss complications observed 7 5 patients procedure related mortality palliative therapies chemotherapy external beam radiotherapy high dose rate brachytherapy done patients outcomes evaluated overall mean survival 134 patients 323 days 59 stents malfunction 41 patients episodes semss malfunction mean survival re interventions 502 9 days survival influenced type tumor sex age conclusions endoscopic multiple semss placement safe effective patients complex mhbs survival independent type complexity mhbs prolonged patients undergoing hdr brachytherapy prompt recognition semss malfunction fundamental survival pubmed","probabilities":0.9799733,"Title":"A 17 years retrospective study on multiple metal stents for complex malignant hilar biliary strictures: Survival, stents patency and outcomes of re-interventions for occluded metal stents","Abstract":"BACKGROUND: Endoscopic placement of SEMSs for malignant hilar biliary strictures (MHBS) is well-established palliative treatment for inoperable patients. Objectives of this study were evaluation of survival and stents patency after placement of multiple SEMS for palliation of complex MHBS. METHODS: Retrospective review of patients with MHBS that underwent ERCP with insertion of multiple SEMSs for palliation. Survival-associated factors and stents patency were analyzed by Cox multivariate analysis. RESULTS: Between January 1998 and January 2015, 740 patients with nonoperable MHBS that underwent ERCP were identified and only 18.2% of these received multiple SEMSs. Complications were observed in 7.5% of the patients with no procedure-related mortality. Palliative therapies (chemotherapy, external beam radiotherapy and high dose rate brachytherapy) were done in some patients, and outcomes were evaluated. Overall mean survival of the 134 patients was 323 days. Of these, 59% did not had stents malfunction while 41% patients had episodes of SEMSs malfunction and mean survival after re-interventions was 502.9 days. Survival was not influenced by type of tumor, sex or age. CONCLUSIONS: Endoscopic multiple SEMSs placement is safe and effective in patients with complex MHBS. Survival is independent from the type and complexity of MHBS while is prolonged in patients undergoing HDR brachytherapy. Prompt recognition of SEMSs malfunction is fundamental for survival.","Source":"PubMed","category":"HUMAN","training_data":"A 17 years retrospective study on multiple metal stents for complex malignant hilar biliary strictures: Survival, stents patency and outcomes of re-interventions for occluded metal stents BACKGROUND: Endoscopic placement of SEMSs for malignant hilar biliary strictures (MHBS) is well-established palliative treatment for inoperable patients. Objectives of this study were evaluation of survival and stents patency after placement of multiple SEMS for palliation of complex MHBS. METHODS: Retrospective review of patients with MHBS that underwent ERCP with insertion of multiple SEMSs for palliation. Survival-associated factors and stents patency were analyzed by Cox multivariate analysis. RESULTS: Between January 1998 and January 2015, 740 patients with nonoperable MHBS that underwent ERCP were identified and only 18.2% of these received multiple SEMSs. Complications were observed in 7.5% of the patients with no procedure-related mortality. Palliative therapies (chemotherapy, external beam radiotherapy and high dose rate brachytherapy) were done in some patients, and outcomes were evaluated. Overall mean survival of the 134 patients was 323 days. Of these, 59% did not had stents malfunction while 41% patients had episodes of SEMSs malfunction and mean survival after re-interventions was 502.9 days. Survival was not influenced by type of tumor, sex or age. CONCLUSIONS: Endoscopic multiple SEMSs placement is safe and effective in patients with complex MHBS. Survival is independent from the type and complexity of MHBS while is prolonged in patients undergoing HDR brachytherapy. Prompt recognition of SEMSs malfunction is fundamental for survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"dna index strong predictive marker intrahepatic cholangiocarcinoma results five year prospective study purpose predictive markers risk stratification among patients intrahepatic cholangiocarcinoma ihc still lacking therefore recent studies focused identifying biological aspects tumors provide information tumor aggressiveness aim study prospectively evaluate prognostic potential dna index patients undergoing liver resection ihc methods prospective long term follow study dna index 65 ihc patients undergoing liver resection assessed dna image cytometry parameter well standard histopathological parameters correlated patient survival results mean dna index 1 69 0 66 range 0 9 4 3 univariate survival analysis showed dna index p 0 024 tumor stage p 0 017 associated patient survival whereas standard histopathological factors predictive value multivariate analysis identified dna index p 0 050 tumor stage p 0 028 independent prognostic parameters conclusions dna index independent predictive marker ihc liver resection superior standard histopathological parameters assessed pre postoperatively therefore dna index might represent promising tool decision making process patients ihc pubmed","probabilities":0.9799733,"Title":"DNA index is a strong predictive marker in intrahepatic cholangiocarcinoma: the results of a five-year prospective study","Abstract":"PURPOSE: Predictive markers for risk stratification among patients with intrahepatic cholangiocarcinoma (IHC) are still lacking. Therefore, recent studies have focused on identifying the biological aspects of tumors that can provide more information about the tumor aggressiveness. The aim of this study was to prospectively evaluate the prognostic potential of the DNA index in patients undergoing liver resection for IHC. METHODS: In a prospective long-term follow-up study, the DNA index of 65 IHC patients undergoing liver resection was assessed by DNA image cytometry, and this parameter, as well as standard histopathological parameters, correlated with the patient survival. RESULTS: The mean DNA index was 1.69 ± 0.66 (range, 0.9-4.3). The univariate survival analysis showed that the DNA index (p = 0.024) and tumor stage (p = 0.017) were associated with patient survival, whereas all other standard histopathological factors had no predictive value. The multivariate analysis identified the DNA index (p = 0.050) and tumor stage (p = 0.028) as independent prognostic parameters. CONCLUSIONS: The DNA index is an independent predictive marker for IHC after liver resection. It is superior to most standard histopathological parameters and can be assessed pre- and postoperatively. Therefore, the DNA index might represent a promising tool in the decision-making process for patients with IHC.","Source":"PubMed","category":"HUMAN","training_data":"DNA index is a strong predictive marker in intrahepatic cholangiocarcinoma: the results of a five-year prospective study PURPOSE: Predictive markers for risk stratification among patients with intrahepatic cholangiocarcinoma (IHC) are still lacking. Therefore, recent studies have focused on identifying the biological aspects of tumors that can provide more information about the tumor aggressiveness. The aim of this study was to prospectively evaluate the prognostic potential of the DNA index in patients undergoing liver resection for IHC. METHODS: In a prospective long-term follow-up study, the DNA index of 65 IHC patients undergoing liver resection was assessed by DNA image cytometry, and this parameter, as well as standard histopathological parameters, correlated with the patient survival. RESULTS: The mean DNA index was 1.69 ± 0.66 (range, 0.9-4.3). The univariate survival analysis showed that the DNA index (p = 0.024) and tumor stage (p = 0.017) were associated with patient survival, whereas all other standard histopathological factors had no predictive value. The multivariate analysis identified the DNA index (p = 0.050) and tumor stage (p = 0.028) as independent prognostic parameters. CONCLUSIONS: The DNA index is an independent predictive marker for IHC after liver resection. It is superior to most standard histopathological parameters and can be assessed pre- and postoperatively. Therefore, the DNA index might represent a promising tool in the decision-making process for patients with IHC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison right left hilar cholangiocarcinoma results french study 399 patients bismuth iii cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Comparison Between Right And Left Hilar Cholangiocarcinoma-Results Of A French Study About 399 Patients With Bismuth Iii Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Comparison Between Right And Left Hilar Cholangiocarcinoma-Results Of A French Study About 399 Patients With Bismuth Iii Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"reproductive factors risk biliary tract cancer population based study background strong female predominance biliary tract cancer btc may related reproductive factors aimed clarify whether parity age first birth influence risk btc methods population based case control study including swedish female male cases cancer gallbladder gbc extra hepatic bile ducts ehcc ampulla vater avc 1960 2008 case 10 age sex matched controls randomly selected conditional logistic regression used calculate odds ratios ors 95 confidence intervals cis adjusted potential confounders results total 1169 cases gbc 432 cases ehcc 295 cases avc included multi nulliparous women men increased risk tumor locations biliary tract compared uniparous women men respectively whereas higher age first birth associated decreased risk gbc women association found men clear differences risk ehcc avc women men conclusion sex hormones may play role etiology gbc associations reproductive factors ehcc avc similar women men support sex hormone hypothesis pubmed","probabilities":0.9799733,"Title":"Reproductive factors and risk of biliary tract cancer in a population-based study","Abstract":"BACKGROUND: The strong female predominance of biliary tract cancer (BTC) may be related to reproductive factors. We aimed to clarify whether parity or age at first birth influence the risk of BTC. METHODS: This was a population-based, case-control study including Swedish female and male cases of cancer of the gallbladder (GBC), extra hepatic bile ducts (EHCC), or the ampulla of Vater (AVC) between 1960 and 2008. For each case, 10 age- and sex-matched controls were randomly selected. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounders. RESULTS: In total, 1169 cases of GBC, 432 cases of EHCC and 295 cases of AVC were included. Multi- and nulliparous women and men had an increased risk of all tumor locations in the biliary tract compared to uniparous women and men, respectively. Whereas higher age at first birth was associated with a decreased risk of GBC in women, no such association was found in men. There were no clear differences in the risk of EHCC and AVC between women and men. CONCLUSION: Sex hormones may play a role in the etiology of GBC. The associations between reproductive factors and EHCC and AVC are similar in women and men, which do not support the sex hormone hypothesis.","Source":"PubMed","category":"HUMAN","training_data":"Reproductive factors and risk of biliary tract cancer in a population-based study BACKGROUND: The strong female predominance of biliary tract cancer (BTC) may be related to reproductive factors. We aimed to clarify whether parity or age at first birth influence the risk of BTC. METHODS: This was a population-based, case-control study including Swedish female and male cases of cancer of the gallbladder (GBC), extra hepatic bile ducts (EHCC), or the ampulla of Vater (AVC) between 1960 and 2008. For each case, 10 age- and sex-matched controls were randomly selected. Conditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs), adjusted for potential confounders. RESULTS: In total, 1169 cases of GBC, 432 cases of EHCC and 295 cases of AVC were included. Multi- and nulliparous women and men had an increased risk of all tumor locations in the biliary tract compared to uniparous women and men, respectively. Whereas higher age at first birth was associated with a decreased risk of GBC in women, no such association was found in men. There were no clear differences in the risk of EHCC and AVC between women and men. CONCLUSION: Sex hormones may play a role in the etiology of GBC. The associations between reproductive factors and EHCC and AVC are similar in women and men, which do not support the sex hormone hypothesis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"h2az regulates tumorigenesis metastasis sensitivity cisplatin intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc fatal malignant tumor liver effective diagnostic biomarkers therapeutic targets icc identified yet high expression h2a histone family member z h2a z high risk factor poor prognosis patients breast cancer primary hepatocellular cancer however significance h2a z expression icc remains unknown present study demonstrated h2a z overexpressed icc expression h2a z correlated poor prognosis patients icc h2a z regulated cell proliferation vitro vivo via h2a z phase kinase associated protein 2 p27 p21 signaling inhibition h2a z reduced cell proliferation induced apoptosis icc addition downregulation h2az reduced tumor metastasis repressing epithelial mesenchymal transition enhanced antitumor effects cisplatin treatment icc overall h2a z promoted cell proliferation epithelial mesenchymal transition icc suggesting h2a z may novel biomarker therapeutic target icc stn","probabilities":0.9467213,"Title":"H2Az Regulates Tumorigenesis Metastasis And Sensitivity To Cisplatin In Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is a fatal, malignant tumor of the liver; effective diagnostic biomarkers and therapeutic targets for ICC have not been identified yet. High expression of H2A histone family member Z (H2A.Z) is a high-risk factor for poor prognosis in patients with breast cancer and primary hepatocellular cancer. However, the significance of H2A.Z and its expression in ICC remains unknown. The present study demonstrated that H2A.Z is overexpressed in ICC and expression of H2A.Z correlated with poor prognosis in patients with ICC. H2A.Z regulated cell proliferation in vitro and in vivo via H2A.Z/S-phase kinase-associated protein 2/p27/p21 signaling. Inhibition of H2A.Z reduced cell proliferation and induced apoptosis in ICC. In addition, downregulation of H2AZ reduced tumor metastasis by repressing epithelial-mesenchymal transition and enhanced the antitumor effects of cisplatin in the treatment of ICC. Overall, H2A.Z promoted cell proliferation and epithelial-mesenchymal transition in ICC, suggesting that H2A.Z may be a novel biomarker and therapeutic target for ICC.","Source":"STN","category":"ANIMAL","training_data":"H2Az Regulates Tumorigenesis Metastasis And Sensitivity To Cisplatin In Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is a fatal, malignant tumor of the liver; effective diagnostic biomarkers and therapeutic targets for ICC have not been identified yet. High expression of H2A histone family member Z (H2A.Z) is a high-risk factor for poor prognosis in patients with breast cancer and primary hepatocellular cancer. However, the significance of H2A.Z and its expression in ICC remains unknown. The present study demonstrated that H2A.Z is overexpressed in ICC and expression of H2A.Z correlated with poor prognosis in patients with ICC. H2A.Z regulated cell proliferation in vitro and in vivo via H2A.Z/S-phase kinase-associated protein 2/p27/p21 signaling. Inhibition of H2A.Z reduced cell proliferation and induced apoptosis in ICC. In addition, downregulation of H2AZ reduced tumor metastasis by repressing epithelial-mesenchymal transition and enhanced the antitumor effects of cisplatin in the treatment of ICC. Overall, H2A.Z promoted cell proliferation and epithelial-mesenchymal transition in ICC, suggesting that H2A.Z may be a novel biomarker and therapeutic target for ICC. STN","prediction_labels":"ANIMAL"},{"cleaned":"gadd45 sirna silencing alters cell survival migration invasion cholangiocarcinoma cells growth arrest dna damage inducible gadd45 stress response protein involved number processes including cell cycle control dna repair survival death control stress signaling depending interactions gadd45 expression dysregulated numerous types cancer functioning either tumor promoter tumor suppressor however functions gadd45 cholangiocarcinoma cca particularly metastasis studied immunohistochemical analysis gadd45 expression revealed 75 histological specimens patients cca expressed high levels gadd45 high gadd45 expression associated metastasis role gadd45 cca examined using sirna mediated gene knockdown hucca 1 human cca cell line established thai patient effects gadd45 downregulation upon cell viability death invasion migration matrix metalloproteinase mmp activity epithelial mesenchymal transition emt marker expression investigated gadd45 knockdown impaired cell viability associated induction apoptosis addition marked reduction invasion migration although mmp activity unaffected impairment metastatic properties accompanied decreased expression emt markers including slug vimentin claudin 1 zona occludens protein 1 whereas e cadherin expression increased present study suggests gadd45 involved regulating viability metastatic potential cca cells may mediated modulation emt pathway google scholar","probabilities":0.9467213,"Title":"Gadd45ß Sirna Silencing Alters The Cell Survival Migration And Invasion Of Cholangiocarcinoma Cells","Abstract":"Growth arrest and DNA damage-inducible-ß (Gadd45ß) is a stress-response protein involved in a number of processes, including cell cycle control, DNA repair, survival and death control, and stress signaling, depending on its interactions. Gadd45ß expression is dysregulated in numerous types of cancer, functioning as either a tumor promoter or a tumor suppressor. However, the functions of Gadd45ß in cholangiocarcinoma (CCA), particularly in metastasis, has not been studied. The immunohistochemical analysis of Gadd45ß expression revealed that 75% of histological specimens from patients with CCA expressed high levels of Gadd45ß, and that high Gadd45ß expression was associated with metastasis. The role of Gadd45ß in CCA was examined using siRNA-mediated gene knockdown in HuCCA-1, a human CCA cell line established from a Thai patient. The effects of Gadd45ß downregulation upon cell viability and death, invasion, migration, matrix metalloproteinase (MMP) activity and epithelial-mesenchymal transition (EMT) marker expression were investigated. Gadd45ß knockdown impaired cell viability, which was associated with the induction of apoptosis. In addition, there was a marked reduction in invasion and migration, although MMP activity was unaffected. Impairment of these metastatic properties was accompanied by the decreased expression of EMT markers, including Slug, vimentin, claudin-1 and zona occludens protein 1, whereas E-cadherin expression was increased. The present study suggests that Gadd45ß is involved in regulating the viability and the metastatic potential of CCA cells, which may be mediated by the modulation of the EMT pathway.","Source":"Google Scholar","category":"ANIMAL","training_data":"Gadd45ß Sirna Silencing Alters The Cell Survival Migration And Invasion Of Cholangiocarcinoma Cells Growth arrest and DNA damage-inducible-ß (Gadd45ß) is a stress-response protein involved in a number of processes, including cell cycle control, DNA repair, survival and death control, and stress signaling, depending on its interactions. Gadd45ß expression is dysregulated in numerous types of cancer, functioning as either a tumor promoter or a tumor suppressor. However, the functions of Gadd45ß in cholangiocarcinoma (CCA), particularly in metastasis, has not been studied. The immunohistochemical analysis of Gadd45ß expression revealed that 75% of histological specimens from patients with CCA expressed high levels of Gadd45ß, and that high Gadd45ß expression was associated with metastasis. The role of Gadd45ß in CCA was examined using siRNA-mediated gene knockdown in HuCCA-1, a human CCA cell line established from a Thai patient. The effects of Gadd45ß downregulation upon cell viability and death, invasion, migration, matrix metalloproteinase (MMP) activity and epithelial-mesenchymal transition (EMT) marker expression were investigated. Gadd45ß knockdown impaired cell viability, which was associated with the induction of apoptosis. In addition, there was a marked reduction in invasion and migration, although MMP activity was unaffected. Impairment of these metastatic properties was accompanied by the decreased expression of EMT markers, including Slug, vimentin, claudin-1 and zona occludens protein 1, whereas E-cadherin expression was increased. The present study suggests that Gadd45ß is involved in regulating the viability and the metastatic potential of CCA cells, which may be mediated by the modulation of the EMT pathway. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"association lymph node status survival patients liver resection hilar cholangiocarcinoma italian multicenter analysis importance prognostic value lymph node ln assessment liver resection hilar cholangiocarcinoma hc still controversial number lns required removed obtain adequate staging well defined objectives evaluate ln status patients liver resection hc clarify prognostic factor number positive lns ln ratio lnr accurate staging minimum number retrieved lns required adequate staging design setting participants retrospective multicenter study patients underwent resection hc january 1 1992 december 31 2007 8 hepatobiliary italian centers last follow assessed july 2014 main outcome measures differences overall survival os according ln status analyzed os results defined actual included patients completed 5 year follow results one hundred seventy five patients 1133 retrieved lns analyzed mean sd age cohort 63 10 years 42 9 75 175 female median number lns examined per patient 6 5 forty percent 70 175 ln metastasis lnr exceeding 0 20 associated significantly lower 5 year os lnr 0 20 less 10 6 vs 24 4 odds ratio 2 434 95 ci 1 020 5 810 p 04 multivariable analysis lnr independent prognostic factor os influenced total number retrieved lns lnr greater 0 20 patients 30 30 1 4 retrieved lns 52 5 21 40 patients least 5 retrieved lns five year os patients 1 5 retrieved lns significantly lower 6 7 retrieved lns least 8 retrieved lns 34 2 64 5 62 7 respectively p 047 five year os significantly improve number retrieved lns greater 6 results confirmed receiver operating characteristic curve analysis performed among n0r0 patients 5 retrieved lns accurate cutoff predict 5 year actual os area curve 0 624 p 004 conclusions relevance lnr exceeding 0 20 independent prognostic factor os n1 patients liver resection hc however lnr influenced total number retrieved lns removal 5 lns minimum number lns required adequate staging pubmed","probabilities":0.9799733,"Title":"Association of Lymph Node Status With Survival in Patients After Liver Resection for Hilar Cholangiocarcinoma in an Italian Multicenter Analysis","Abstract":"IMPORTANCE: The prognostic value of lymph node (LN) assessment after liver resection for hilar cholangiocarcinoma (HC) is still controversial, and the number of LNs required to be removed to obtain adequate staging is not well defined. OBJECTIVES: To evaluate the LN status in patients after liver resection for HC and to clarify which prognostic factor (the number of positive LNs or the LN ratio [LNR]) was most accurate for staging and what minimum number of retrieved LNs was required for adequate staging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective multicenter study of patients who underwent resection for HC between January 1, 1992, and December 31, 2007, at 8 hepatobiliary Italian centers. The last follow-up was assessed in July 2014. MAIN OUTCOME AND MEASURES: Differences in overall survival (OS) according to the LN status were analyzed. The OS results were defined as actual because all included patients completed a 5-year follow-up. RESULTS: One-hundred seventy-five patients with 1133 retrieved LNs were analyzed. The mean (SD) age of the cohort was 63 (10) years, and 42.9% (75 of 175) were female. The median number of LNs examined per patient was 6.5. Forty percent (70 of 175) had LN metastasis. An LNR exceeding 0.20 was associated with significantly lower 5-year OS than an LNR of 0.20 or less (10.6% vs 24.4%; odds ratio, 2.434; 95% CI, 1.020-5.810; P = .04). On multivariable analysis, the LNR was the only independent prognostic factor for OS but was influenced by the total number of retrieved LNs. The LNR was greater than 0.20 in all patients (30 of 30) with 1 to 4 retrieved LNs and in 52.5% (21 of 40) of patients with at least 5 retrieved LNs. Five-year OS in patients with 1 to 5 retrieved LNs was significantly lower than that in those with 6 to 7 retrieved LNs and those with at least 8 retrieved LNs (34.2%, 64.5%, and 62.7%, respectively; P = .047). Five-year OS did not significantly improve when the number of retrieved LNs was greater than 6. These results were confirmed in a receiver operating characteristic curve analysis performed among N0R0 patients, in whom 5 retrieved LNs was the most accurate cutoff to predict 5-year actual OS (area under the curve, 0.624; P = .004). CONCLUSIONS AND RELEVANCE: An LNR exceeding 0.20 was the only independent prognostic factor for OS in N1 patients after liver resection for HC. However, the LNR was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging.","Source":"PubMed","category":"HUMAN","training_data":"Association of Lymph Node Status With Survival in Patients After Liver Resection for Hilar Cholangiocarcinoma in an Italian Multicenter Analysis IMPORTANCE: The prognostic value of lymph node (LN) assessment after liver resection for hilar cholangiocarcinoma (HC) is still controversial, and the number of LNs required to be removed to obtain adequate staging is not well defined. OBJECTIVES: To evaluate the LN status in patients after liver resection for HC and to clarify which prognostic factor (the number of positive LNs or the LN ratio [LNR]) was most accurate for staging and what minimum number of retrieved LNs was required for adequate staging. DESIGN, SETTING, AND PARTICIPANTS: Retrospective multicenter study of patients who underwent resection for HC between January 1, 1992, and December 31, 2007, at 8 hepatobiliary Italian centers. The last follow-up was assessed in July 2014. MAIN OUTCOME AND MEASURES: Differences in overall survival (OS) according to the LN status were analyzed. The OS results were defined as actual because all included patients completed a 5-year follow-up. RESULTS: One-hundred seventy-five patients with 1133 retrieved LNs were analyzed. The mean (SD) age of the cohort was 63 (10) years, and 42.9% (75 of 175) were female. The median number of LNs examined per patient was 6.5. Forty percent (70 of 175) had LN metastasis. An LNR exceeding 0.20 was associated with significantly lower 5-year OS than an LNR of 0.20 or less (10.6% vs 24.4%; odds ratio, 2.434; 95% CI, 1.020-5.810; P = .04). On multivariable analysis, the LNR was the only independent prognostic factor for OS but was influenced by the total number of retrieved LNs. The LNR was greater than 0.20 in all patients (30 of 30) with 1 to 4 retrieved LNs and in 52.5% (21 of 40) of patients with at least 5 retrieved LNs. Five-year OS in patients with 1 to 5 retrieved LNs was significantly lower than that in those with 6 to 7 retrieved LNs and those with at least 8 retrieved LNs (34.2%, 64.5%, and 62.7%, respectively; P = .047). Five-year OS did not significantly improve when the number of retrieved LNs was greater than 6. These results were confirmed in a receiver operating characteristic curve analysis performed among N0R0 patients, in whom 5 retrieved LNs was the most accurate cutoff to predict 5-year actual OS (area under the curve, 0.624; P = .004). CONCLUSIONS AND RELEVANCE: An LNR exceeding 0.20 was the only independent prognostic factor for OS in N1 patients after liver resection for HC. However, the LNR was influenced by the total number of retrieved LNs, and removal of more than 5 LNs was the minimum number of LNs required for adequate staging. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical usefulness perioperative c reactive protein albumin ratio patients intrahepatic cholangiocarcinoma retrospective single institutional study background aim prognoses patients cancer predicted basis preoperative nutrition inflammation based scores however predicting prognostic impact undergoing surgery remains challenging study investigated usefulness perioperative c reactive protein albumin crp alb ratio patients intrahepatic cholangiocarcinoma icc patients methods retrospectively investigated 80 patients undergone curative resection primary icc april 2002 december 2017 identified time perioperative crp alb ratio influences prognosis investigated correlations among perioperative crp alb ratio clinicopathological features patient outcomes results perioperative crp alb ratios significantly associated shorter overall survival os high crp alb ratio pod14 high crp alb ratio pod 14 significantly associated older age male sex presence postoperative complications finally high crp alb ratio pod 14 independent prognostic factor poor os conclusion crp alb ratio pod 14 may useful prognostic factor patients icc undergone curative resections pubmed","probabilities":0.9799733,"Title":"Clinical Usefulness of Perioperative C-reactive Protein/Albumin Ratio in Patients With Intrahepatic Cholangiocarcinoma: A Retrospective Single Institutional Study","Abstract":"BACKGROUND/AIM: Prognoses of patients with cancer can be predicted on the basis of preoperative nutrition- or inflammation-based scores; however, predicting the prognostic impact of undergoing surgery remains challenging. In this study, we investigated the usefulness of the perioperative C-reactive protein/albumin (CRP/Alb) ratio in patients with intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: We retrospectively investigated 80 patients who had undergone curative resection of primary ICC between April 2002 and December 2017. We identified the time at which perioperative CRP/Alb ratio most influences the prognosis, and investigated the correlations among the perioperative CRP/Alb ratio, clinicopathological features and patient outcomes. RESULTS: The only perioperative CRP/Alb ratios significantly associated with shorter overall survival (OS) was a high CRP/Alb ratio on POD14. High CRP/Alb ratio on POD 14 was significantly associated with older age, male sex, and the presence of postoperative complications. Finally, a high CRP/Alb ratio at POD 14 was an independent prognostic factor for poor OS. CONCLUSION: CRP/Alb ratio on POD 14 may be a useful prognostic factor in patients with ICC who have undergone curative resections.","Source":"PubMed","category":"HUMAN","training_data":"Clinical Usefulness of Perioperative C-reactive Protein/Albumin Ratio in Patients With Intrahepatic Cholangiocarcinoma: A Retrospective Single Institutional Study BACKGROUND/AIM: Prognoses of patients with cancer can be predicted on the basis of preoperative nutrition- or inflammation-based scores; however, predicting the prognostic impact of undergoing surgery remains challenging. In this study, we investigated the usefulness of the perioperative C-reactive protein/albumin (CRP/Alb) ratio in patients with intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: We retrospectively investigated 80 patients who had undergone curative resection of primary ICC between April 2002 and December 2017. We identified the time at which perioperative CRP/Alb ratio most influences the prognosis, and investigated the correlations among the perioperative CRP/Alb ratio, clinicopathological features and patient outcomes. RESULTS: The only perioperative CRP/Alb ratios significantly associated with shorter overall survival (OS) was a high CRP/Alb ratio on POD14. High CRP/Alb ratio on POD 14 was significantly associated with older age, male sex, and the presence of postoperative complications. Finally, a high CRP/Alb ratio at POD 14 was an independent prognostic factor for poor OS. CONCLUSION: CRP/Alb ratio on POD 14 may be a useful prognostic factor in patients with ICC who have undergone curative resections. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ercp directed radiofrequency ablation photodynamic therapy associated comparable survival treatment unresectable cholangiocarcinoma background cholangiocarcinoma cca malignancy poor 5 year survival rate 5 10 ercp directed radiofrequency ablation rfa photodynamic therapy pdt performed palliative therapy unresectable cca ercp pdt associated improved survival compared stent placement alone however ercp directed rfa directly compared pdt patients cca objective compare overall survival patients unresectable cca underwent palliative ercp directed rfa versus pdt design retrospective cohort study setting tertiary care academic medical center patients forty eight patients unresectable cca underwent ercp directed ablative therapy palliation unresectable cca interventions ercp directed rfa pdt main outcome measurements overall survival kaplan meier analysis initial treatment either rfa pdt results patients underwent rfa n 16 demonstrated overall survival similar underwent pdt n 32 median survival 9 6 versus 7 5 months respectively p 799 patient age p 45 sex p 52 lead time p 59 presentation initial rfa pdt significant association survival presence distant metastasis inversely associated survival hazard ratio 3 55 95 confidence interval 1 29 9 77 p 014 patients underwent rfa compared pdt lower mean number plastic stents placed per month 0 45 vs 1 10 p 001 also episodes stent occlusion 0 06 vs 0 02 p 008 cholangitis 0 13 vs 0 05 p 008 per month limitations retrospective single center design conclusions survival ercp directed rfa pdt statistically different patients unresectable cca randomized controlled trial warranted validate preliminary results pubmed","probabilities":0.9799733,"Title":"ERCP-directed radiofrequency ablation and photodynamic therapy are associated with comparable survival in the treatment of unresectable cholangiocarcinoma","Abstract":"BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy with a poor 5-year survival rate (5%-10%). ERCP-directed radiofrequency ablation (RFA) or photodynamic therapy (PDT) can be performed as palliative therapy for unresectable CCA. ERCP with PDT is associated with improved survival compared with stent placement alone. However, ERCP-directed RFA has not been directly compared with PDT in patients with CCA. OBJECTIVE: To compare overall survival in patients with unresectable CCA who underwent palliative ERCP-directed RFA versus PDT. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENTS: Forty-eight patients with unresectable CCA who underwent ERCP-directed ablative therapy for palliation of unresectable CCA. INTERVENTIONS: ERCP-directed RFA or PDT. MAIN OUTCOME MEASUREMENTS: Overall survival by Kaplan-Meier analysis after initial treatment with either RFA or PDT. RESULTS: Patients who underwent RFA (n = 16) demonstrated an overall survival similar to that of those who underwent PDT (n = 32), with a median survival of 9.6 versus 7.5 months, respectively (P = .799). Patient age (P = .45), sex (P = .52), and lead time (P = .59) from presentation to initial RFA or PDT had no significant association with survival. The presence of distant metastasis was inversely associated with survival (hazard ratio 3.55; 95% confidence interval, 1.29-9.77; P = .014). Patients who underwent RFA (compared with PDT) had a lower mean number of plastic stents placed per month (0.45 vs 1.10, P = .001) but also had more episodes of stent occlusion (0.06 vs 0.02, P = .008) and cholangitis (0.13 vs 0.05, P = .008) per month. LIMITATIONS: Retrospective, single-center design. CONCLUSIONS: Survival after ERCP-directed RFA and PDT was not statistically different in patients with unresectable CCA. A randomized, controlled trial is warranted to validate these preliminary results.","Source":"PubMed","category":"HUMAN","training_data":"ERCP-directed radiofrequency ablation and photodynamic therapy are associated with comparable survival in the treatment of unresectable cholangiocarcinoma BACKGROUND: Cholangiocarcinoma (CCA) is a malignancy with a poor 5-year survival rate (5%-10%). ERCP-directed radiofrequency ablation (RFA) or photodynamic therapy (PDT) can be performed as palliative therapy for unresectable CCA. ERCP with PDT is associated with improved survival compared with stent placement alone. However, ERCP-directed RFA has not been directly compared with PDT in patients with CCA. OBJECTIVE: To compare overall survival in patients with unresectable CCA who underwent palliative ERCP-directed RFA versus PDT. DESIGN: Retrospective cohort study. SETTING: Tertiary-care academic medical center. PATIENTS: Forty-eight patients with unresectable CCA who underwent ERCP-directed ablative therapy for palliation of unresectable CCA. INTERVENTIONS: ERCP-directed RFA or PDT. MAIN OUTCOME MEASUREMENTS: Overall survival by Kaplan-Meier analysis after initial treatment with either RFA or PDT. RESULTS: Patients who underwent RFA (n = 16) demonstrated an overall survival similar to that of those who underwent PDT (n = 32), with a median survival of 9.6 versus 7.5 months, respectively (P = .799). Patient age (P = .45), sex (P = .52), and lead time (P = .59) from presentation to initial RFA or PDT had no significant association with survival. The presence of distant metastasis was inversely associated with survival (hazard ratio 3.55; 95% confidence interval, 1.29-9.77; P = .014). Patients who underwent RFA (compared with PDT) had a lower mean number of plastic stents placed per month (0.45 vs 1.10, P = .001) but also had more episodes of stent occlusion (0.06 vs 0.02, P = .008) and cholangitis (0.13 vs 0.05, P = .008) per month. LIMITATIONS: Retrospective, single-center design. CONCLUSIONS: Survival after ERCP-directed RFA and PDT was not statistically different in patients with unresectable CCA. A randomized, controlled trial is warranted to validate these preliminary results. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic immunohistochemical biomarkers chemotherapy efficacy biliary tract cancer systematic review meta analysis introduction chemotherapy mainstay systemic treatment biliary tract cancer btc however treatment response chemotherapy varies patients currently prognostic biomarkers chemotherapy efficacy considered use clinical practice systematic review conducted evaluate prognostic value immunohistochemical biomarkers chemotherapy patients resected well advanced btc method medline embase databases searched march 2017 studies evaluated biomarker expression immunohistochemistry resected advanced btc patients treated chemotherapy primary endpoints overall survival os disease progression free survival dfs pfs result twenty six studies including total 1348 patients 26 different biomarkers met inclusion criteria included review frequently studied prognostic biomarkers btc human equilibrative nucleoside transporter 1 hent1 ribonucleotide reductase m1 rrm1 excision repair cross complementation 1 ercc1 meta analysis patients treated gemcitabine based chemotherapy high hent1 expression associated longer os hr 0 43 95 ci 0 28 0 64 dfs pfs hr 0 45 95 ci 0 33 0 61 conclusion hent1 promising prognostic biomarker gemcitabine based chemotherapy resected well advanced btc validated selection patients chemotherapy pubmed","probabilities":0.8684211,"Title":"Prognostic immunohistochemical biomarkers of chemotherapy efficacy in biliary tract cancer: A systematic review and meta-analysis","Abstract":"INTRODUCTION: Chemotherapy is the mainstay of systemic treatment of biliary tract cancer (BTC). However, the treatment response to chemotherapy varies between patients. Currently, no prognostic biomarkers for chemotherapy efficacy have been considered for use in clinical practice. A systematic review was conducted to evaluate the prognostic value of immunohistochemical biomarkers for chemotherapy in patients with resected as well as with advanced BTC. METHOD: Medline and EMBASE databases were searched up to March 2017 for studies that evaluated biomarker expression by immunohistochemistry in resected or advanced BTC patients treated with chemotherapy. The primary endpoints were overall survival (OS) and disease or progression free survival (DFS or PFS). RESULT: Twenty-six studies, including a total of 1348 patients and 26 different biomarkers, met the inclusion criteria and were included in this review. The most frequently studied prognostic biomarkers in BTC were the human Equilibrative Nucleoside Transporter 1 (hENT1), Ribonucleotide Reductase M1 (RRM1), and excision repair cross-complementation 1 (ERCC1). In the meta-analysis of patients treated with gemcitabine-based chemotherapy, high hENT1 expression was associated with longer OS (HR 0.43, 95% CI: 0.28 to 0.64) and DFS/PFS (HR 0.45, 95% CI: 0.33 to 0.61). CONCLUSION: hENT1 is a promising prognostic biomarker for gemcitabine-based chemotherapy in resected as well as in advanced BTC and should be further validated for the selection of patients for chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic immunohistochemical biomarkers of chemotherapy efficacy in biliary tract cancer: A systematic review and meta-analysis INTRODUCTION: Chemotherapy is the mainstay of systemic treatment of biliary tract cancer (BTC). However, the treatment response to chemotherapy varies between patients. Currently, no prognostic biomarkers for chemotherapy efficacy have been considered for use in clinical practice. A systematic review was conducted to evaluate the prognostic value of immunohistochemical biomarkers for chemotherapy in patients with resected as well as with advanced BTC. METHOD: Medline and EMBASE databases were searched up to March 2017 for studies that evaluated biomarker expression by immunohistochemistry in resected or advanced BTC patients treated with chemotherapy. The primary endpoints were overall survival (OS) and disease or progression free survival (DFS or PFS). RESULT: Twenty-six studies, including a total of 1348 patients and 26 different biomarkers, met the inclusion criteria and were included in this review. The most frequently studied prognostic biomarkers in BTC were the human Equilibrative Nucleoside Transporter 1 (hENT1), Ribonucleotide Reductase M1 (RRM1), and excision repair cross-complementation 1 (ERCC1). In the meta-analysis of patients treated with gemcitabine-based chemotherapy, high hENT1 expression was associated with longer OS (HR 0.43, 95% CI: 0.28 to 0.64) and DFS/PFS (HR 0.45, 95% CI: 0.33 to 0.61). CONCLUSION: hENT1 is a promising prognostic biomarker for gemcitabine-based chemotherapy in resected as well as in advanced BTC and should be further validated for the selection of patients for chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors survival curative resection distal cholangiocarcinoma perineural invasion lymphovascular invasion purpose purpose study elucidate prognostic factors distal cholangiocarcinoma curative resection assess significance perineural invasion pni lymphovascular invasion lvi prognostic factors methods retrospective analysis 91 patients underwent radical surgery distal cholangiocarcinoma march 2004 october 2011 performed analyzed survival rate prognostic factors affecting survival results overall 1 3 5 year survival rates 84 1 49 7 38 9 respectively univariate analysis prognostic factors influencing survival histological differentiation lymph node ln involvement tnm stage multivariate analysis ln metastasis independent prognostic factor although patients pni tended show poorer survival statistically significant factor 3 5 year os 62 0 54 6 vs 42 8 30 9 p 0 166 patients total lymph node count tlnc 11 less pni significant prognostic factor however significant factor patients tlnc 11 overall lvi influence patient survival conclusions ln metastasis significant prognostic factor curative resection distal cholangiocarcinoma cases adequate dissection performed appeared pni lvi influence survival stn","probabilities":0.9799733,"Title":"The Prognostic Factors For Survival After Curative Resection Of Distal Cholangiocarcinoma: Perineural Invasion And Lymphovascular Invasion","Abstract":"Purpose: The purpose of this study was to elucidate the prognostic factors for distal cholangiocarcinoma after curative resection, and to assess the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) as prognostic factors. \r\n\r\n Methods: A retrospective analysis of 91 patients who underwent radical surgery for distal cholangiocarcinoma between March 2004 and October 2011 was performed. We analyzed the survival rate and prognostic factors affecting the survival. \r\n\r\n Results: The overall 1-, 3- and 5-year survival rates were 84.1, 49.7 and 38.9 %, respectively. In the univariate analysis, the prognostic factors influencing the survival were the histological differentiation, lymph node (LN) involvement and TNM stage. In the multivariate analysis, LN metastasis was the only independent prognostic factor. Although patients with PNI tended to show poorer survival, it was not a statistically significant factor (3- and 5-year OS; 62.0 and 54.6 % vs. 42.8 and 30.9 %, P = 0.166). In the patients with a total lymph node count (TLNC) of 11 or less, PNI was a significant prognostic factor; however, it was not a significant factor in the patients with a TLNC over 11. Overall, the LVI had no influence on the patient survival. \r\n\r\n Conclusions: LN metastasis was the only significant prognostic factor after the curative resection of distal cholangiocarcinoma. In cases where adequate dissection was performed, it appeared that the PNI and LVI had no influence on the survival.","Source":"STN","category":"HUMAN","training_data":"The Prognostic Factors For Survival After Curative Resection Of Distal Cholangiocarcinoma: Perineural Invasion And Lymphovascular Invasion Purpose: The purpose of this study was to elucidate the prognostic factors for distal cholangiocarcinoma after curative resection, and to assess the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) as prognostic factors. \r\n\r\n Methods: A retrospective analysis of 91 patients who underwent radical surgery for distal cholangiocarcinoma between March 2004 and October 2011 was performed. We analyzed the survival rate and prognostic factors affecting the survival. \r\n\r\n Results: The overall 1-, 3- and 5-year survival rates were 84.1, 49.7 and 38.9 %, respectively. In the univariate analysis, the prognostic factors influencing the survival were the histological differentiation, lymph node (LN) involvement and TNM stage. In the multivariate analysis, LN metastasis was the only independent prognostic factor. Although patients with PNI tended to show poorer survival, it was not a statistically significant factor (3- and 5-year OS; 62.0 and 54.6 % vs. 42.8 and 30.9 %, P = 0.166). In the patients with a total lymph node count (TLNC) of 11 or less, PNI was a significant prognostic factor; however, it was not a significant factor in the patients with a TLNC over 11. Overall, the LVI had no influence on the patient survival. \r\n\r\n Conclusions: LN metastasis was the only significant prognostic factor after the curative resection of distal cholangiocarcinoma. In cases where adequate dissection was performed, it appeared that the PNI and LVI had no influence on the survival. STN","prediction_labels":"HUMAN"},{"cleaned":"annual report nation status cancer 1975 2012 featuring increasing incidence liver cancer background annual updates cancer occurrence trends united states provided ongoing collaboration among american cancer society acs centers disease control prevention cdc national cancer institute nci north american association central cancer registries naaccr annual report highlights increasing burden liver intrahepatic bile duct liver cancers methods cancer incidence data obtained cdc nci naaccr data cancer deaths obtained cdc national center health statistics nchs annual percent changes incidence death rates age adjusted 2000 us standard population cancers combined leading cancers among men women estimated joinpoint analysis long term trends incidence 1992 2012 mortality 1975 2012 short term trends 2008 2012 depth analysis liver cancer incidence included age period cohort analysis incidence based estimation person years life lost disease using nchs multiple causes death data hepatitis c virus hcv liver cancer associated death rates examined 1999 2013 results among men women major racial ethnic groups death rates continued decline cancers combined cancer sites overall cancer death rate sexes combined decreased 1 5 per year 2003 2012 overall incidence rates decreased among men remained stable among women 2003 2012 among men women deaths liver cancer increased highest rate cancer sites liver cancer incidence rates increased sharply second thyroid cancer men twice incidence rate liver cancer women rates increased age sexes among non hispanic nh white nh black hispanic men women liver cancer incidence rates higher persons born 1938 1947 birth cohort contrast minimal birth cohort effect nh asian pacific islanders apis nh black men hispanic men lowest median age death 60 62 years respectively highest average person years life lost per death 21 20 years respectively liver cancer hcv liver cancer associated death rates highest among decedents born 1945 1965 conclusions overall cancer incidence mortality declined among men although cancer incidence stable among women mortality declined burden liver cancer growing equally distributed throughout population efforts vaccinate populations vulnerable hepatitis b virus hbv infection identify treat living hcv hbv infection metabolic conditions alcoholic liver disease causes cirrhosis effective reducing incidence mortality liver cancer cancer 2016 122 1312 1337 2016 american cancer society pubmed","probabilities":0.9799733,"Title":"Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer","Abstract":"BACKGROUND: Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers. METHODS: Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2012 and mortality for 1975-2012) and short-term trends (2008-2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013. RESULTS: Among men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence rates were higher for persons born after the 1938 to 1947 birth cohort. In contrast, there was a minimal birth cohort effect for NH Asian and Pacific Islanders (APIs). NH black men and Hispanic men had the lowest median age at death (60 and 62 years, respectively) and the highest average person-years of life lost per death (21 and 20 years, respectively) from liver cancer. HCV and liver cancer-associated death rates were highest among decedents who were born during 1945 through 1965. CONCLUSIONS: Overall, cancer incidence and mortality declined among men; and, although cancer incidence was stable among women, mortality declined. The burden of liver cancer is growing and is not equally distributed throughout the population. Efforts to vaccinate populations that are vulnerable to hepatitis B virus (HBV) infection and to identify and treat those living with HCV or HBV infection, metabolic conditions, alcoholic liver disease, or other causes of cirrhosis can be effective in reducing the incidence and mortality of liver cancer. Cancer 2016;122:1312-1337. © 2016 American Cancer Society.","Source":"PubMed","category":"HUMAN","training_data":"Annual Report to the Nation on the Status of Cancer, 1975-2012, featuring the increasing incidence of liver cancer BACKGROUND: Annual updates on cancer occurrence and trends in the United States are provided through an ongoing collaboration among the American Cancer Society (ACS), the Centers for Disease Control and Prevention (CDC), the National Cancer Institute (NCI), and the North American Association of Central Cancer Registries (NAACCR). This annual report highlights the increasing burden of liver and intrahepatic bile duct (liver) cancers. METHODS: Cancer incidence data were obtained from the CDC, NCI, and NAACCR; data about cancer deaths were obtained from the CDC's National Center for Health Statistics (NCHS). Annual percent changes in incidence and death rates (age-adjusted to the 2000 US Standard Population) for all cancers combined and for the leading cancers among men and women were estimated by joinpoint analysis of long-term trends (incidence for 1992-2012 and mortality for 1975-2012) and short-term trends (2008-2012). In-depth analysis of liver cancer incidence included an age-period-cohort analysis and an incidence-based estimation of person-years of life lost because of the disease. By using NCHS multiple causes of death data, hepatitis C virus (HCV) and liver cancer-associated death rates were examined from 1999 through 2013. RESULTS: Among men and women of all major racial and ethnic groups, death rates continued to decline for all cancers combined and for most cancer sites; the overall cancer death rate (for both sexes combined) decreased by 1.5% per year from 2003 to 2012. Overall, incidence rates decreased among men and remained stable among women from 2003 to 2012. Among both men and women, deaths from liver cancer increased at the highest rate of all cancer sites, and liver cancer incidence rates increased sharply, second only to thyroid cancer. Men had more than twice the incidence rate of liver cancer than women, and rates increased with age for both sexes. Among non-Hispanic (NH) white, NH black, and Hispanic men and women, liver cancer incidence rates were higher for persons born after the 1938 to 1947 birth cohort. In contrast, there was a minimal birth cohort effect for NH Asian and Pacific Islanders (APIs). NH black men and Hispanic men had the lowest median age at death (60 and 62 years, respectively) and the highest average person-years of life lost per death (21 and 20 years, respectively) from liver cancer. HCV and liver cancer-associated death rates were highest among decedents who were born during 1945 through 1965. CONCLUSIONS: Overall, cancer incidence and mortality declined among men; and, although cancer incidence was stable among women, mortality declined. The burden of liver cancer is growing and is not equally distributed throughout the population. Efforts to vaccinate populations that are vulnerable to hepatitis B virus (HBV) infection and to identify and treat those living with HCV or HBV infection, metabolic conditions, alcoholic liver disease, or other causes of cirrhosis can be effective in reducing the incidence and mortality of liver cancer. Cancer 2016;122:1312-1337. © 2016 American Cancer Society. PubMed","prediction_labels":"HUMAN"},{"cleaned":"conditional probability survival gallbladder carcinoma apt prognostic tool long term survivors background gallbladder carcinoma gbc often presents advanced stage despite radical resection nodal harvest prognosis remains poor conventional survival statistics account time elapsed diagnosis may carry relevant prognostic information long term survivors study sought estimate conditional probability survival cs patients gbc methods patients gbc identified surveillance epidemiology end results seer database 1988 2012 overall probability survival os estimated using kaplan meier method cumulative incidence method employed calculate cs results 15 046 gbc patients identified stage iv disease common presentation n 5625 surgical intervention reported 9 720 65 patients cholecystectomies n 8254 outnumbering radical resections n 1116 3 year os stages 18 conditional probability surviving additional 3 years cs3 1 2 3 years diagnosis 42 57 66 respectively stage iii iv disease 3 year os rates 19 3 respectively cs3 increased progressively year survived 33 17 1 year 51 34 2 years 60 56 3 years discussion conditional probability survival favorable patients surviving one year diagnosis shows increasing trend time improvements survival substantial patients adverse initial prognosis conditional survival provides valuable information prognosis patients curative surgery basis follow guidelines google scholar","probabilities":0.9799733,"Title":"Conditional Probability Of Survival In Gallbladder Carcinoma: An Apt Prognostic Tool For Long-Term Survivors","Abstract":"Background: Gallbladder carcinoma (GBC) often presents in an advanced stage and despite radical resection and nodal harvest, prognosis remains poor. Conventional survival statistics do not account for time elapsed from diagnosis and may not carry relevant prognostic information for long term survivors. This study sought to estimate the conditional probability of survival (CS) in patients of GBC. Methods: Patients with GBC were identified from the Surveillance, Epidemiology and End Results (SEER) database (1988-2012). Overall probability of survival (OS) was estimated using Kaplan-Meier method. Cumulative incidence method was employed to calculate CS. Results: Of 15,046 GBC patients identified, Stage IV disease was the most common presentation (n=5625). Surgical intervention was reported in 9,720(65%) patients with cholecystectomies (n=8254) outnumbering radical resections (n=1116). 3-year OS for all stages was 18% and conditional probability of surviving additional 3 years (CS3) at 1, 2 and 3 years from diagnosis was 42%, 57% and 66% respectively. Stage III and IV disease had 3-year OS rates of 19% and 3% respectively while CS3 increased progressively with each year survived(33% and 17% at 1 year, 51% and 34% at 2 years, 60% and 56% at 3 years). Discussion: Conditional probability of survival is favorable in patients surviving one year from diagnosis and shows an increasing trend with time. Improvements in survival are more substantial in patients with adverse initial prognosis. Conditional survival provides valuable information on prognosis to patients after curative surgery and can be the basis of follow-up guidelines.","Source":"Google Scholar","category":"HUMAN","training_data":"Conditional Probability Of Survival In Gallbladder Carcinoma: An Apt Prognostic Tool For Long-Term Survivors Background: Gallbladder carcinoma (GBC) often presents in an advanced stage and despite radical resection and nodal harvest, prognosis remains poor. Conventional survival statistics do not account for time elapsed from diagnosis and may not carry relevant prognostic information for long term survivors. This study sought to estimate the conditional probability of survival (CS) in patients of GBC. Methods: Patients with GBC were identified from the Surveillance, Epidemiology and End Results (SEER) database (1988-2012). Overall probability of survival (OS) was estimated using Kaplan-Meier method. Cumulative incidence method was employed to calculate CS. Results: Of 15,046 GBC patients identified, Stage IV disease was the most common presentation (n=5625). Surgical intervention was reported in 9,720(65%) patients with cholecystectomies (n=8254) outnumbering radical resections (n=1116). 3-year OS for all stages was 18% and conditional probability of surviving additional 3 years (CS3) at 1, 2 and 3 years from diagnosis was 42%, 57% and 66% respectively. Stage III and IV disease had 3-year OS rates of 19% and 3% respectively while CS3 increased progressively with each year survived(33% and 17% at 1 year, 51% and 34% at 2 years, 60% and 56% at 3 years). Discussion: Conditional probability of survival is favorable in patients surviving one year from diagnosis and shows an increasing trend with time. Improvements in survival are more substantial in patients with adverse initial prognosis. Conditional survival provides valuable information on prognosis to patients after curative surgery and can be the basis of follow-up guidelines. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"blood expression matrix metalloproteinases 8 9 inducers s100a8 s100a9 supports diagnosis prognosis pdac associated diabetes mellitus background based knowledge matrix metalloproteinases mmps s100a8 a9 synergistically work causing pdac associated type 2 diabetes mellitus t2dm verified whether tissue blood mmp8 mmp9 s100a8 s100a9 expression might help distinguishing pdac among diabetics methods relative quantification mmp8 mmp9 s100a8 s100a9 mrna performed tissues obtained 8 pdac 4 chronic pancreatitis chrpa 4 non pdac tumors pbmcs obtained 30 controls 43 t2dm 41 chrpa 91 pdac 33 pancreatic biliary tract tumors results t2dm observed pdac 66 pancreatic biliary tract tumors 64 chrpa 70 diabetics without pdac mmp9 tissue expression increased p 0 05 mmps increased pdac mmp9 increased also pancreatic biliary tract tumors pbmcs diabetics mmp9 independently associated pdac p 0 025 failed enhance ca 19 9 discriminant efficacy highly reduced s100a9 expression found 7 pdac significantly correlated reduced overall survival p 0 015 conclusions increased expression tissue blood mmp9 reflects presence pdac associated diabetes mellitus finding fits hypothesized role mmps part complex network linking cancer diabetes stn","probabilities":0.9285714,"Title":"Blood Expression Of Matrix Metalloproteinases 8 And 9 And Of Their Inducers S100A8 And S100A9 Supports Diagnosis And Prognosis Of Pdac-Associated Diabetes Mellitus","Abstract":"Background: Based on the knowledge that matrix metalloproteinases (MMPs) and S100A8/A9 synergistically work in causing PDAC-associated type 2 diabetes mellitus (T2DM), we verified whether tissue and blood MMP8, MMP9, S100A8 and S100A9 expression might help in distinguishing PDAC among diabetics. \r\n\r\n Methods: Relative quantification of MMP8, MMP9, S100A8 and S100A9 mRNA was performed in tissues obtained from 8 PDAC, 4 chronic pancreatitis (ChrPa), 4 non-PDAC tumors and in PBMCs obtained from 30 controls, 43 T2DM, 41 ChrPa, 91 PDAC and 33 pancreatic-biliary tract tumors. \r\n\r\n Results: T2DM was observed in PDAC (66%), in pancreatic-biliary tract tumors (64%) and in ChrPa (70%). In diabetics, with or without PDAC, MMP9 tissue expression was increased (p<0.05). Both MMPs increased in PDAC and MMP9 increased also in pancreatic-biliary tract tumors PBMCs. In diabetics, MMP9 was independently associated with PDAC (p=0.025), but failed to enhance CA 19-9 discriminant efficacy. A highly reduced S100A9 expression, found in 7 PDAC, was significantly correlated with a reduced overall survival (p=0.015). \r\n\r\n Conclusions: An increased expression of tissue and blood MMP9 reflects the presence of PDAC-associated diabetes mellitus. This finding fits with the hypothesized role of MMPs as part of the complex network linking cancer to diabetes.","Source":"STN","category":"ANIMAL","training_data":"Blood Expression Of Matrix Metalloproteinases 8 And 9 And Of Their Inducers S100A8 And S100A9 Supports Diagnosis And Prognosis Of Pdac-Associated Diabetes Mellitus Background: Based on the knowledge that matrix metalloproteinases (MMPs) and S100A8/A9 synergistically work in causing PDAC-associated type 2 diabetes mellitus (T2DM), we verified whether tissue and blood MMP8, MMP9, S100A8 and S100A9 expression might help in distinguishing PDAC among diabetics. \r\n\r\n Methods: Relative quantification of MMP8, MMP9, S100A8 and S100A9 mRNA was performed in tissues obtained from 8 PDAC, 4 chronic pancreatitis (ChrPa), 4 non-PDAC tumors and in PBMCs obtained from 30 controls, 43 T2DM, 41 ChrPa, 91 PDAC and 33 pancreatic-biliary tract tumors. \r\n\r\n Results: T2DM was observed in PDAC (66%), in pancreatic-biliary tract tumors (64%) and in ChrPa (70%). In diabetics, with or without PDAC, MMP9 tissue expression was increased (p<0.05). Both MMPs increased in PDAC and MMP9 increased also in pancreatic-biliary tract tumors PBMCs. In diabetics, MMP9 was independently associated with PDAC (p=0.025), but failed to enhance CA 19-9 discriminant efficacy. A highly reduced S100A9 expression, found in 7 PDAC, was significantly correlated with a reduced overall survival (p=0.015). \r\n\r\n Conclusions: An increased expression of tissue and blood MMP9 reflects the presence of PDAC-associated diabetes mellitus. This finding fits with the hypothesized role of MMPs as part of the complex network linking cancer to diabetes. STN","prediction_labels":"ANIMAL"},{"cleaned":"expression clinical significance piwil2 hilar cholangiocarcinoma tissues cell lines objective study explore relationship piwi like protein 2 piwil2 clinicopathological charac teristics prognosis radical resection accomplish analyzed piwil2 expression hilar cholangiocarcinoma tissues cell lines piwil2 expression detected immunohistochemistry 41 hilar cholangiocarcinoma samples 10 control tissues western blotting immunocytofluorescence used investigate piwil2 expression cholangiocarcinoma cell line qbc939 bile duct epithelial cell line hibepic univariate multivariate surviv al analyses performed using kaplan meier method hilar cholangiocarcinoma patients underwent radical resection piwil2 expression significantly higher hilar cholangiocarcinoma tissues qbc939 cells control tissues hibepic cells respectively p 0 05 poorly moderately differentiated cholan giocarcinoma tissues significantly higher piwil2 expression well differentiated tissues p 0 05 univariate analysis demonstrated high piwil2 expression associated shorter survival time radical resection p 0 05 multivariate analysis showed pi wil2 expression independent prognostic factor radical re section hilar cholangiocarcinoma p 0 05 piwil2 expression also associated tumor node metastasis stage differentiation piwil2 independent prognostic factor radical resection hilar cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Expression And Clinical Significance Of Piwil2 In Hilar Cholangiocarcinoma Tissues And Cell Lines","Abstract":"The objective of this study was to explore the relationship between PIWI-like protein 2 (PIWIL2) and clinicopathological charac-teristics and prognosis after radical resection. To accomplish this, we analyzed PIWIL2 expression in hilar cholangiocarcinoma tissues and cell lines. PIWIL2 expression was detected by immunohistochemistry in 41 hilar cholangiocarcinoma samples and 10 control tissues. Western blotting and immunocytofluorescence were used to investigate PIWIL2 expression in the cholangiocarcinoma cell line QBC939 and the bile duct epithelial cell line HIBEpic. Univariate and multivariate surviv-al analyses were performed using the Kaplan-Meier method for hilar cholangiocarcinoma patients who underwent radical resection. PIWIL2 expression was significantly higher in the hilar cholangiocarcinoma tissues and QBC939 cells than in control tissues and HIBEpic cells, respectively (P < 0.05). Poorly and moderately differentiated cholan-giocarcinoma tissues had significantly higher PIWIL2 expression than well-differentiated tissues (P < 0.05). Univariate analysis demonstrated that high PIWIL2 expression was associated with shorter survival time after radical resection (P < 0.05). Multivariate analysis showed that PI-WIL2 expression was an independent prognostic factor after radical re-section of hilar cholangiocarcinoma (P < 0.05). PIWIL2 expression was also associated with tumor-node-metastasis stage and differentiation. PIWIL2 was an independent prognostic factor after radical resection of hilar cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Expression And Clinical Significance Of Piwil2 In Hilar Cholangiocarcinoma Tissues And Cell Lines The objective of this study was to explore the relationship between PIWI-like protein 2 (PIWIL2) and clinicopathological charac-teristics and prognosis after radical resection. To accomplish this, we analyzed PIWIL2 expression in hilar cholangiocarcinoma tissues and cell lines. PIWIL2 expression was detected by immunohistochemistry in 41 hilar cholangiocarcinoma samples and 10 control tissues. Western blotting and immunocytofluorescence were used to investigate PIWIL2 expression in the cholangiocarcinoma cell line QBC939 and the bile duct epithelial cell line HIBEpic. Univariate and multivariate surviv-al analyses were performed using the Kaplan-Meier method for hilar cholangiocarcinoma patients who underwent radical resection. PIWIL2 expression was significantly higher in the hilar cholangiocarcinoma tissues and QBC939 cells than in control tissues and HIBEpic cells, respectively (P < 0.05). Poorly and moderately differentiated cholan-giocarcinoma tissues had significantly higher PIWIL2 expression than well-differentiated tissues (P < 0.05). Univariate analysis demonstrated that high PIWIL2 expression was associated with shorter survival time after radical resection (P < 0.05). Multivariate analysis showed that PI-WIL2 expression was an independent prognostic factor after radical re-section of hilar cholangiocarcinoma (P < 0.05). PIWIL2 expression was also associated with tumor-node-metastasis stage and differentiation. PIWIL2 was an independent prognostic factor after radical resection of hilar cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"induction phosphatase shatterproof 2 evodiamine suppresses proliferation invasion human cholangiocarcinoma cholangiocarcinoma cca one common fatal carcinomas well known lack effective treatment thus novel therapeutic strategies greatly needed evodiamine quinozole alkaloid isolated evodia rutaecarpa bentham demonstrated exhibit anti tumor effects many cancer cells however little known terms effects cholangiocarcinoma study studied whether traditional chinese medicine serve new potential therapeutic drugs treat cca discovered evodiamine inhibited cca cell proliferation induced apoptosis moreover evodiamine inhibited cca cell migration invasion mechanistically studies demonstrated evodiamine inhibited activation il 6 induced stat3 signaling activation inhibitory effect likely due upregulation phosphatase shatterproof 2 shp 2 negative feedback regulator il 6 stat3 blockage shp 2 small interference rna sirna abolished evodiamine induced il 6 stat3 signaling inhibition moreover vivo experiment showed evodiamine inhibited tumor growth nude mice bearing tfk 1 xenografts summary results implied evodiamine promising anti cancer agent treatment cca mechanism likely due inhibition il 6 stat3 signaling upregulating expression levels shp 2 google scholar","probabilities":0.9467213,"Title":"Induction Of Phosphatase Shatterproof 2 By Evodiamine Suppresses The Proliferation And Invasion Of Human Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is one of the most common fatal carcinomas and is well known to be lack of effective treatment. Thus, novel therapeutic strategies are greatly needed. Evodiamine, a quinozole alkaloid isolated from evodia rutaecarpa Bentham, has been demonstrated to exhibit anti-tumor effects on many cancer cells. However, little is known in terms of the effects on cholangiocarcinoma. In this study, we studied whether this traditional Chinese Medicine could serve as new potential therapeutic drugs to treat CCA. We discovered that evodiamine inhibited CCA cell proliferation and induced apoptosis. Moreover, evodiamine inhibited CCA cell migration and invasion. Mechanistically, our studies demonstrated that evodiamine inhibited the activation of IL-6 -induced STAT3 signaling activation, and the inhibitory effect was likely due to the upregulation of phosphatase shatterproof 2 (SHP-2), a negative feedback regulator of IL-6/STAT3. Blockage of SHP-2 through small interference RNA (siRNA) abolished the evodiamine -induced IL-6/STAT3 signaling inhibition. Moreover, in vivo experiment showed evodiamine inhibited the tumor growth of nude mice bearing TFK-1 xenografts. In summary, our results implied evodiamine as a promising anti-cancer agent in the treatment of CCA, and the mechanism is likely due to the inhibition of IL-6/STAT3 signaling with upregulating the expression levels of SHP-2.","Source":"Google Scholar","category":"ANIMAL","training_data":"Induction Of Phosphatase Shatterproof 2 By Evodiamine Suppresses The Proliferation And Invasion Of Human Cholangiocarcinoma Cholangiocarcinoma (CCA) is one of the most common fatal carcinomas and is well known to be lack of effective treatment. Thus, novel therapeutic strategies are greatly needed. Evodiamine, a quinozole alkaloid isolated from evodia rutaecarpa Bentham, has been demonstrated to exhibit anti-tumor effects on many cancer cells. However, little is known in terms of the effects on cholangiocarcinoma. In this study, we studied whether this traditional Chinese Medicine could serve as new potential therapeutic drugs to treat CCA. We discovered that evodiamine inhibited CCA cell proliferation and induced apoptosis. Moreover, evodiamine inhibited CCA cell migration and invasion. Mechanistically, our studies demonstrated that evodiamine inhibited the activation of IL-6 -induced STAT3 signaling activation, and the inhibitory effect was likely due to the upregulation of phosphatase shatterproof 2 (SHP-2), a negative feedback regulator of IL-6/STAT3. Blockage of SHP-2 through small interference RNA (siRNA) abolished the evodiamine -induced IL-6/STAT3 signaling inhibition. Moreover, in vivo experiment showed evodiamine inhibited the tumor growth of nude mice bearing TFK-1 xenografts. In summary, our results implied evodiamine as a promising anti-cancer agent in the treatment of CCA, and the mechanism is likely due to the inhibition of IL-6/STAT3 signaling with upregulating the expression levels of SHP-2. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"cholangiocarcinoma principles current trends background cholangiocarcinoma cca lethal cancer biliary epithelium originating liver intrahepatic confluence right left hepatic ducts hilar extrahepatic bile ducts rare malignancy associated poor prognosis data sources searched pubmed medline database relevant articles published 1989 2008 search terms used related cholangiocarcinoma treatment although language restrictions imposed initially full text review final analysis resources permitted review articles published english review deals treatment cholangiocarcinoma principles current trends results risks prognostic factors symptoms differential diagnosis thoroughly discussed addition tools preoperative diagnosis endoscopic retrograde cholangiopancreatography digital image analysis fluorescence situ hybridization magnetic resonance cholangiopancreatography reviewed moreover treatment cca discussed conclusions curative treatment available surgical management unfortunately many patients present unresectable tumors majority die within year diagnosis surgical treatment involves major resections liver pancreas bile duct considerable mortality morbidity however selected cases indicated appropriate management aggressive surgery may achieve good outcome prolonged survival expectancy pubmed","probabilities":0.9799733,"Title":"Cholangiocarcinoma: principles and current trends","Abstract":"BACKGROUND: Cholangiocarcinoma (CCA) is a lethal cancer of the biliary epithelium, originating from the liver (intrahepatic), at the confluence of the right and left hepatic ducts (hilar) or in the extrahepatic bile ducts. It is a rare malignancy associated with poor prognosis. DATA SOURCES: We searched the PubMed/MEDLINE database for relevant articles published from 1989 to 2008. The search terms used were related to \"cholangiocarcinoma\" and its \"treatment\". Although no language restrictions were imposed initially, for the full-text review and final analysis, our resources only permitted the review of articles published in English. This review deals with the treatment of cholangiocarcinoma, the principles and the current trends. RESULTS: The risks and prognostic factors, symptoms and differential diagnosis are thoroughly discussed. In addition, the tools of preoperative diagnosis such as endoscopic retrograde cholangiopancreatography, digital image analysis, fluorescence in situ hybridization and magnetic resonance cholangiopancreatography are reviewed. Moreover, the treatment of CCA is discussed. CONCLUSIONS: The only curative treatment available is surgical management. Unfortunately, many patients present with unresectable tumors, the majority of whom die within a year of diagnosis. Surgical treatment involves major resections of the liver, pancreas and bile duct, with considerable mortality and morbidity. However, in selected cases and where indicated, appropriate management with aggressive surgery may achieve a good outcome with a prolonged survival expectancy.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma: principles and current trends BACKGROUND: Cholangiocarcinoma (CCA) is a lethal cancer of the biliary epithelium, originating from the liver (intrahepatic), at the confluence of the right and left hepatic ducts (hilar) or in the extrahepatic bile ducts. It is a rare malignancy associated with poor prognosis. DATA SOURCES: We searched the PubMed/MEDLINE database for relevant articles published from 1989 to 2008. The search terms used were related to \"cholangiocarcinoma\" and its \"treatment\". Although no language restrictions were imposed initially, for the full-text review and final analysis, our resources only permitted the review of articles published in English. This review deals with the treatment of cholangiocarcinoma, the principles and the current trends. RESULTS: The risks and prognostic factors, symptoms and differential diagnosis are thoroughly discussed. In addition, the tools of preoperative diagnosis such as endoscopic retrograde cholangiopancreatography, digital image analysis, fluorescence in situ hybridization and magnetic resonance cholangiopancreatography are reviewed. Moreover, the treatment of CCA is discussed. CONCLUSIONS: The only curative treatment available is surgical management. Unfortunately, many patients present with unresectable tumors, the majority of whom die within a year of diagnosis. Surgical treatment involves major resections of the liver, pancreas and bile duct, with considerable mortality and morbidity. However, in selected cases and where indicated, appropriate management with aggressive surgery may achieve a good outcome with a prolonged survival expectancy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic predictability new american joint committee cancer 8th staging system distal bile duct cancer limited usefulness compared 7th staging system background new 8th american joint committee cancer ajcc staging recently released major changes distal bile duct dbd cancer staging however clinical validation needed changes widely implemented methods study performed evaluate prognostic predictability 8th ajcc staging compared 7th using c statistics results total 293 consecutive patients curative intended surgery enrolled significant difference 5 year survival rate 7th t1 t2 p 0 123 significant difference t2 t3 p 0 039 significant differences pairwise comparisons 8th stage t1 vs t2 p 0 001 t2 vs t3 p 0 014 number regional lymph node metastases also showed prognostic predictability 8th n stage showed comparable prognostic predictability 7th 95 confidential intervals c 0 043 0 097 n 0 001 0 008 conclusions 8th ajcc staging dbd cancer better prognostic predictability 7th stage previous pathologic results become useless unless reviewed entirely therefore introduction ajcc 8th staging reconsidered especially new staging pubmed","probabilities":0.9799733,"Title":"Prognostic predictability of the new American Joint Committee on Cancer 8th staging system for distal bile duct cancer: limited usefulness compared with the 7th staging system","Abstract":"BACKGROUND: The new 8th American Joint Committee on Cancer (AJCC) staging has recently been released and there are major changes in distal bile duct (DBD) cancer staging. However, clinical validation is needed before the changes can be widely implemented. METHODS: This study was performed to evaluate the prognostic predictability of the 8th AJCC staging compared with that of the 7th using C statistics. RESULTS: A total of 293 consecutive patients who had curative-intended surgery were enrolled. There was no significant difference of the 5-year survival rate between 7th T1 and T2 (P = 0.123), but significant difference between T2 and T3 (P = 0.039). There were significant differences in pairwise comparisons between the 8th T stage (T1 vs. T2, P = 0.001; T2 vs. T3, P = 0.014). The number of regional lymph node metastases also showed prognostic predictability. The 8th T and N stage both showed comparable prognostic predictability with the 7th (95% confidential intervals for C; T, -0.043 -0.097, N, -0.001 - 0.008). CONCLUSIONS: The 8th AJCC staging for DBD cancer does not have better prognostic predictability than the 7th stage does. The previous pathologic results would become useless unless they were reviewed entirely. Therefore, introduction of the AJCC 8th staging has to be reconsidered, especially for new T staging.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic predictability of the new American Joint Committee on Cancer 8th staging system for distal bile duct cancer: limited usefulness compared with the 7th staging system BACKGROUND: The new 8th American Joint Committee on Cancer (AJCC) staging has recently been released and there are major changes in distal bile duct (DBD) cancer staging. However, clinical validation is needed before the changes can be widely implemented. METHODS: This study was performed to evaluate the prognostic predictability of the 8th AJCC staging compared with that of the 7th using C statistics. RESULTS: A total of 293 consecutive patients who had curative-intended surgery were enrolled. There was no significant difference of the 5-year survival rate between 7th T1 and T2 (P = 0.123), but significant difference between T2 and T3 (P = 0.039). There were significant differences in pairwise comparisons between the 8th T stage (T1 vs. T2, P = 0.001; T2 vs. T3, P = 0.014). The number of regional lymph node metastases also showed prognostic predictability. The 8th T and N stage both showed comparable prognostic predictability with the 7th (95% confidential intervals for C; T, -0.043 -0.097, N, -0.001 - 0.008). CONCLUSIONS: The 8th AJCC staging for DBD cancer does not have better prognostic predictability than the 7th stage does. The previous pathologic results would become useless unless they were reviewed entirely. Therefore, introduction of the AJCC 8th staging has to be reconsidered, especially for new T staging. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cytotoxic activities effects atractylodin eudesmol cell cycle arrest apoptosis cholangiocarcinoma cell line cholangiocarcinoma cca cancer bile duct high mortality rate particularly thailand clinical efficacy standard chemotherapeutics remains unsatisfactory therefore discovery development new alternative drugs high efficacy tolerability needed aim study investigate cytotoxic activity well underlying mechanisms atractylodin eudesmol exert activities cca cell growth inhibition cell cycle arrest cell apoptosis effects compounds cell cytotoxicity cell cycle arrest cell apoptosis analyzed using mtt assay bd cycletest plus dna kit fitc annexin v apoptosis detection kit respectively cytotoxic activities compounds concentration time dependent ic50 mean sd atractylodin eudesmol 41 66 2 51 39 33 1 15 g ml respectively promoted cell cycle arrest g1 phase induced cell apoptosis activation caspase 3 7 highest activity observed 48 h exposure results suggest mechanisms least part explain cell cytotoxic anti cca activity atractylodin eudesmol shown vitro vivo models stn","probabilities":0.9467213,"Title":"Cytotoxic Activities And Effects Of Atractylodin And ß-Eudesmol On The Cell Cycle Arrest And Apoptosis On Cholangiocarcinoma Cell Line","Abstract":"Cholangiocarcinoma (CCA) is the cancer of bile duct with high mortality rate particularly in Thailand. The clinical efficacy of the standard chemotherapeutics remains unsatisfactory, and therefore, discovery and development of the new alternative drugs with high efficacy and tolerability is needed. The aim of the study was to investigate cytotoxic activity as well as the underlying mechanisms through which atractylodin and β-eudesmol exert their activities on CCA cell growth inhibition, cell cycle arrest, and cell apoptosis. Effects of the compounds on cell cytotoxicity, cell cycle arrest, and cell apoptosis were analyzed using MTT assay, BD Cycletest™ Plus DNA kit, and FITC Annexin V Apoptosis Detection Kit I, respectively. The cytotoxic activities of both compounds were concentration- and time-dependent. The IC50 [mean (SD)] of atractylodin and β-eudesmol were 41.66 (2.51) and 39.33 (1.15) μg/ml respectively. Both promoted cell cycle arrest at G1 phase, and induced cell apoptosis through activation of caspase-3/7. The highest activity was observed at 48 h of exposure. Results suggest that these mechanisms are at least in part, explain the cell cytotoxic and anti-CCA activity of atractylodin and β-eudesmol shown in vitro and in vivo models.","Source":"STN","category":"ANIMAL","training_data":"Cytotoxic Activities And Effects Of Atractylodin And ß-Eudesmol On The Cell Cycle Arrest And Apoptosis On Cholangiocarcinoma Cell Line Cholangiocarcinoma (CCA) is the cancer of bile duct with high mortality rate particularly in Thailand. The clinical efficacy of the standard chemotherapeutics remains unsatisfactory, and therefore, discovery and development of the new alternative drugs with high efficacy and tolerability is needed. The aim of the study was to investigate cytotoxic activity as well as the underlying mechanisms through which atractylodin and β-eudesmol exert their activities on CCA cell growth inhibition, cell cycle arrest, and cell apoptosis. Effects of the compounds on cell cytotoxicity, cell cycle arrest, and cell apoptosis were analyzed using MTT assay, BD Cycletest™ Plus DNA kit, and FITC Annexin V Apoptosis Detection Kit I, respectively. The cytotoxic activities of both compounds were concentration- and time-dependent. The IC50 [mean (SD)] of atractylodin and β-eudesmol were 41.66 (2.51) and 39.33 (1.15) μg/ml respectively. Both promoted cell cycle arrest at G1 phase, and induced cell apoptosis through activation of caspase-3/7. The highest activity was observed at 48 h of exposure. Results suggest that these mechanisms are at least in part, explain the cell cytotoxic and anti-CCA activity of atractylodin and β-eudesmol shown in vitro and in vivo models. STN","prediction_labels":"ANIMAL"},{"cleaned":"expression matrix metalloproteinase 2 extracellular matrix metalloproteinase inducer unfavorable postoperative prognostic factors intrahepatic cholangiocarcinoma many investigators indicated overexpression amplification matrix metalloproteinase 2 mmp 2 extracellular matrix metalloproteinase inducer emmprin independent prognostic factors primary tumors studied expression tissues intrahepatic cholangiocarcinoma ihcca normal bile ducts discussed occurrence development ihcca another goal explore possible association mmp 2 emmprin clinicopathologic parameters prognosis ihcca mmp 2 emmprin expression 106 cases ihcca tissues 15 cases normal bile ducts examined immunohistochemical staining association mmp 2 emmprin expression clinicopathologic parameters patients prognosis analyzed positive expression levels mmp 2 emmprin associated significantly various clinicopathologic risk factors poor histologic differentiation p 0 03 0 02 higher tnm stages p 0 02 0 01 decreased tumor specific survival particular tumor specific survival rate patients mmp 2 emmprin expression lowest p 0 01 using cox regression analysis 89 patients conjoined expressions mmp 2 emmprin mmp 2 emmprin histologic differentiation clinical tnm stages tumorous tissues independent prognostic indicators ihcca p 0 01 p 0 01 p 0 02 p 0 01 p 0 01 respectively mmp 2 emmprin expression primary tumor predicts unfavorable prognosis ihcca suggesting crucial role two markers progression human ihcca stn","probabilities":1.0,"Title":"Expression Of Matrix Metalloproteinase 2 And Extracellular Matrix Metalloproteinase Inducer Are Unfavorable Postoperative Prognostic Factors In Intrahepatic Cholangiocarcinoma","Abstract":"Many investigators have indicated that overexpression and amplification of matrix metalloproteinase 2 (MMP-2) and extracellular matrix metalloproteinase inducer (EMMPRIN) are independent prognostic factors for primary tumors. We studied expression of them in tissues from intrahepatic cholangiocarcinoma (IHCCA) and normal bile ducts, and discussed the occurrence and development of IHCCA. Another goal was to explore possible association of MMP-2 and EMMPRIN with clinicopathologic parameters and prognosis of IHCCA. MMP-2 and EMMPRIN expression in 106 cases of IHCCA tissues and 15 cases of normal bile ducts were examined by immunohistochemical staining. Then, the association of MMP-2 and EMMPRIN expression with clinicopathologic parameters and patients' prognosis was analyzed. The positive expression levels of MMP-2 and EMMPRIN associated significantly with various clinicopathologic risk factors, such as poor histologic differentiation (p = 0.03, 0.02), higher TNM stages (p = 0.02, 0.01) and decreased tumor-specific survival. In particular, the tumor-specific survival rate of the patients with MMP-2+/ EMMPRIN+expression was the lowest (p < 0.01). Using Cox regression analysis of the 89 patients, the conjoined expressions of MMP-2-/ EMMPRIN-, MMP-2+/ EMMPRIN +, histologic differentiation, and the clinical TNM stages of tumorous tissues were independent prognostic indicators of IHCCA (p < 0.01, p < 0.01, p = 0.02, p = 0.01 and p = 0.01, respectively). MMP-2 and EMMPRIN expression in primary tumor predicts an unfavorable prognosis in IHCCA, suggesting a crucial role of the two markers in progression of human IHCCA.","Source":"STN","category":"ANIMAL","training_data":"Expression Of Matrix Metalloproteinase 2 And Extracellular Matrix Metalloproteinase Inducer Are Unfavorable Postoperative Prognostic Factors In Intrahepatic Cholangiocarcinoma Many investigators have indicated that overexpression and amplification of matrix metalloproteinase 2 (MMP-2) and extracellular matrix metalloproteinase inducer (EMMPRIN) are independent prognostic factors for primary tumors. We studied expression of them in tissues from intrahepatic cholangiocarcinoma (IHCCA) and normal bile ducts, and discussed the occurrence and development of IHCCA. Another goal was to explore possible association of MMP-2 and EMMPRIN with clinicopathologic parameters and prognosis of IHCCA. MMP-2 and EMMPRIN expression in 106 cases of IHCCA tissues and 15 cases of normal bile ducts were examined by immunohistochemical staining. Then, the association of MMP-2 and EMMPRIN expression with clinicopathologic parameters and patients' prognosis was analyzed. The positive expression levels of MMP-2 and EMMPRIN associated significantly with various clinicopathologic risk factors, such as poor histologic differentiation (p = 0.03, 0.02), higher TNM stages (p = 0.02, 0.01) and decreased tumor-specific survival. In particular, the tumor-specific survival rate of the patients with MMP-2+/ EMMPRIN+expression was the lowest (p < 0.01). Using Cox regression analysis of the 89 patients, the conjoined expressions of MMP-2-/ EMMPRIN-, MMP-2+/ EMMPRIN +, histologic differentiation, and the clinical TNM stages of tumorous tissues were independent prognostic indicators of IHCCA (p < 0.01, p < 0.01, p = 0.02, p = 0.01 and p = 0.01, respectively). MMP-2 and EMMPRIN expression in primary tumor predicts an unfavorable prognosis in IHCCA, suggesting a crucial role of the two markers in progression of human IHCCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"outcomes patients recurrent intrahepatic cholangiocarcinoma surgery background study aimed analyze postoperative outcomes patients recurrent intrahepatic cholangiocarcinoma icc determine prognostic factors addition study investigated effects various treatment methods patients recurrent icc methods retrospective study analyzed postoperative outcomes prognostic factors recurrent icc occurred 81 128 patients underwent hepatic resection icc april 2001 april 2013 addition outcomes number treatment methods assessed patients recurrent icc results resection 128 patients icc survival rates 73 1 year 52 3 years 43 5 years recurrent icc developed 81 patients 56 men 25 women median age 63 years median time initial resection recurrence 9 months range 0 124 months median survival time recurrence 8 months range 0 108 months recurrence overall survival rates 47 1 year 23 3 years 15 5 years multivariate analysis showed disease free survival time shorter 1 year bile duct invasion significant prognostic factors among treatment methods local management surgery transarterial chemoembolization radiofrequency ablation effective select cases localized intrahepatic extrahepatic recurrence conclusion active local treatment e surgery transarterial chemoembolization tace radiofrequency ablation rfa may improve survival patients localized icc recurrence pubmed","probabilities":0.9799733,"Title":"Outcomes for Patients with Recurrent Intrahepatic Cholangiocarcinoma After Surgery","Abstract":"BACKGROUND: This study aimed to analyze the postoperative outcomes for patients with recurrent intrahepatic cholangiocarcinoma (ICC) and to determine the prognostic factors. In addition, this study investigated the effects of various treatment methods for patients with recurrent ICC. METHODS: This retrospective study analyzed the postoperative outcomes and prognostic factors of recurrent ICC that occurred for 81 of 128 patients who underwent hepatic resection for ICC between April 2001 and April 2013. In addition, the outcomes for a number of treatment methods were assessed for patients with recurrent ICC. RESULTS: After resection, the 128 patients with ICC had survival rates of 73 % at 1 year, 52 % at 3 years, and 43 % at 5 years. Recurrent ICC developed in 81 patients (56 men and 25 women) with a median age of 63 years. The median time from initial resection to recurrence was 9 months (range, 0-124 months), and the median survival time after recurrence was 8 months (range, 0-108 months). After recurrence, the overall survival rates were 47 % at 1 year, 23 % at 3 years, and 15 % at 5 years. Multivariate analysis showed disease-free survival time shorter than 1 year and bile duct invasion to be significant prognostic factors. Among the treatment methods, local management such as surgery, transarterial chemoembolization, and radiofrequency ablation were effective in select cases with localized intrahepatic and extrahepatic recurrence. CONCLUSION: Active local treatment (i.e., surgery, transarterial chemoembolization [TACE], and radiofrequency ablation [RFA]) may improve survival for patients with localized ICC recurrence.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes for Patients with Recurrent Intrahepatic Cholangiocarcinoma After Surgery BACKGROUND: This study aimed to analyze the postoperative outcomes for patients with recurrent intrahepatic cholangiocarcinoma (ICC) and to determine the prognostic factors. In addition, this study investigated the effects of various treatment methods for patients with recurrent ICC. METHODS: This retrospective study analyzed the postoperative outcomes and prognostic factors of recurrent ICC that occurred for 81 of 128 patients who underwent hepatic resection for ICC between April 2001 and April 2013. In addition, the outcomes for a number of treatment methods were assessed for patients with recurrent ICC. RESULTS: After resection, the 128 patients with ICC had survival rates of 73 % at 1 year, 52 % at 3 years, and 43 % at 5 years. Recurrent ICC developed in 81 patients (56 men and 25 women) with a median age of 63 years. The median time from initial resection to recurrence was 9 months (range, 0-124 months), and the median survival time after recurrence was 8 months (range, 0-108 months). After recurrence, the overall survival rates were 47 % at 1 year, 23 % at 3 years, and 15 % at 5 years. Multivariate analysis showed disease-free survival time shorter than 1 year and bile duct invasion to be significant prognostic factors. Among the treatment methods, local management such as surgery, transarterial chemoembolization, and radiofrequency ablation were effective in select cases with localized intrahepatic and extrahepatic recurrence. CONCLUSION: Active local treatment (i.e., surgery, transarterial chemoembolization [TACE], and radiofrequency ablation [RFA]) may improve survival for patients with localized ICC recurrence. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative inflammation negative impact survival resection extrahepatic bile duct cancer background significance presence preoperative inflammation prognosis patients extrahepatic bile duct cancer bdca evaluated methods clinical data 84 patients underwent surgery bdca august 2003 may 2009 reviewed survival analysis performed patients classified two groups according presence preoperative cholangitis group cholangitis n 59 group b cholangitis n 25 results differences sex mean age tnm stage biliary drainage type resection radicality two groups p 0 05 3 year disease specific survival dss disease free survival dfs rates group b patients 21 5 11 9 respectively significantly lower group patients 66 1 57 3 respectively p 0 013 0 001 respectively multivariate analysis showed preoperative inflammation lymph node metastasis independent prognostic factors overall survival os p 0 021 relative risk rr 2 224 p 0 015 rr 2 367 respectively dfs p 0 014 rr 2 192 p 0 013 rr 2 240 respectively rates angiolymphatic perineural invasion higher group b group p 0 016 0 030 respectively conclusions presence preoperative inflammation independent poor prognostic factor os dfs patients bdca stn","probabilities":0.9799733,"Title":"Preoperative Inflammation Has A Negative Impact On Survival After Resection Of Extrahepatic Bile Duct Cancer","Abstract":"Background: The significance of the presence of preoperative inflammation for the prognosis of patients with extrahepatic bile duct cancer (BDCA) was evaluated. \r\n\r\n Methods: The clinical data of 84 patients who underwent surgery for BDCA from August 2003 to May 2009 were reviewed, and survival analysis was performed. The patients were classified into two groups according to the presence of preoperative cholangitis: Group A had no cholangitis (n = 59), and group B had cholangitis (n = 25). \r\n\r\n Results: There were no differences in sex, mean age, TNM stage, biliary drainage, type of resection, or radicality between the two groups (p > 0.05). The 3-year disease-specific survival (DSS) and disease-free survival (DFS) rates for the group B patients (21.5 and 11.9 %, respectively) were significantly lower than those for the group A patients (66.1 and 57.3 %, respectively; p = 0.013 and 0.001, respectively). The multivariate analysis showed that preoperative inflammation and lymph node metastasis were the independent prognostic factors for both overall survival (OS) [p = 0.021, relative risk (RR) = 2.224 and p = 0.015, RR = 2.367, respectively] and DFS (p = 0.014; RR = 2.192 and p = 0.013; RR = 2.240, respectively). The rates of angiolymphatic and perineural invasion were higher for group B than those for group A (p = 0.016 and 0.030, respectively). \r\n\r\n Conclusions: The presence of preoperative inflammation is an independent poor prognostic factor for OS and DFS for patients with BDCA.","Source":"STN","category":"HUMAN","training_data":"Preoperative Inflammation Has A Negative Impact On Survival After Resection Of Extrahepatic Bile Duct Cancer Background: The significance of the presence of preoperative inflammation for the prognosis of patients with extrahepatic bile duct cancer (BDCA) was evaluated. \r\n\r\n Methods: The clinical data of 84 patients who underwent surgery for BDCA from August 2003 to May 2009 were reviewed, and survival analysis was performed. The patients were classified into two groups according to the presence of preoperative cholangitis: Group A had no cholangitis (n = 59), and group B had cholangitis (n = 25). \r\n\r\n Results: There were no differences in sex, mean age, TNM stage, biliary drainage, type of resection, or radicality between the two groups (p > 0.05). The 3-year disease-specific survival (DSS) and disease-free survival (DFS) rates for the group B patients (21.5 and 11.9 %, respectively) were significantly lower than those for the group A patients (66.1 and 57.3 %, respectively; p = 0.013 and 0.001, respectively). The multivariate analysis showed that preoperative inflammation and lymph node metastasis were the independent prognostic factors for both overall survival (OS) [p = 0.021, relative risk (RR) = 2.224 and p = 0.015, RR = 2.367, respectively] and DFS (p = 0.014; RR = 2.192 and p = 0.013; RR = 2.240, respectively). The rates of angiolymphatic and perineural invasion were higher for group B than those for group A (p = 0.016 and 0.030, respectively). \r\n\r\n Conclusions: The presence of preoperative inflammation is an independent poor prognostic factor for OS and DFS for patients with BDCA. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic influence lymph node ratio following pancreaticoduodenectomy ampullary adenocarcinoma background survival surgery ampullary cancer remains poor prognostic factors including tumour stage lymph node ln status tumour grade identified described lymph node ratio lnr number involved lns compared numberexaminedhasbeenprognosticinpancreaticadenocarcinoma wesoughttoassessthe prognostic value lnr consecutive series ampullary adenocarcinomas undergoing pancreaticoduodenectomy methodsretrospectivereviewofaprospectivedatabaseofpancreaticoduodenectomiesperformedbetween1997and2008wasundertaken clinicopathologic data collected lnr calculated patients positive ln status grouped 1 lnr 0 2 lnr 0 01 0 2 3 lnr 0 2 0 4 4 lnr 0 4 pa survival outcome compared using kaplar meier cox proportional hazards analysis results 95 ampullary adenocarcinomas identified median survival cohort 31 2months 95 ci 18 2 67 4 median number lns harvested 20 0 95 ci 18 5 22 1 ln involvement associated aggressive tumour characteristicsincludinglymphovascularinvasion tumourstageandnotablyanelevatedpre operative c reactiveproteinconcentration p 0 05 overalllnstatusinfluencedsurvivalwithmedian survivalforthe38 44 7 negativeresectionsbeing124months 95 ci 96 8 152 8 versus 23 3months node positive disease 95 ci 18 1 36 5 increasing lnr associated decreased survival lnr 0 01 0 2 40 0months lnr 0 2 0 4 18 3months lnr 0 4 10 1months onmultivariateanalysislnstatus hazardratio4 6 95 ci2 6 9 6 perineural invasion hazard ratio 3 3 95 ci 1 5 7 3 maintained significance conclusion positive ln status ampullary adenocarcinoma strongly independent predictor poor outcome pancreaticoduodenectomyiscurativein65 ofpatientswithnode negativedisease amongstthelnpositiveampullaryadenocarcinomaresectionslnrwasinverselyassociated outcome google scholar","probabilities":0.9799733,"Title":"The Prognostic Influence Of Lymph Node Ratio Following Pancreaticoduodenectomy For Ampullary Adenocarcinoma","Abstract":"Background Survival after surgery for ampullary cancer remains poor. Prognostic factors including tumour stage, lymph node (LN) status, and tumour grade have been identified. Described as the lymph node ratio (LNR), the number of involved LNs compared to the numberexaminedhasbeenprognosticinpancreaticadenocarcinoma.Wesoughttoassessthe prognostic value of LNR on a consecutive series of ampullary adenocarcinomas undergoing pancreaticoduodenectomy.MethodsRetrospectivereviewofaprospectivedatabaseofpancreaticoduodenectomiesperformedbetween1997and2008wasundertaken.Clinicopathologic data was collected and the LNR calculated. Patients with positive LN status were grouped into: (1) LNR=0; (2) LNR 0.01-0.2; (3) LNR ≥0.2-0.4 and (4) LNR ≥0.4. Pa Survival outcome was compared using Kaplar-Meier/Cox proportional hazards analysis. Results 95 ampullary adenocarcinomas were identified with a median survival for the cohort being 31.2months (95%CI:18.2-67.4). The median number of LNs harvested was 20.0 (95%CI:18.5-22.1). LN involvement was associated with other aggressive tumour characteristicsincludinglymphovascularinvasion,tumourstageandnotablyanelevatedpre-operative C-reactiveproteinconcentration(p<0.05).OverallLNstatusinfluencedsurvivalwithmedian survivalforthe38(44.7%)negativeresectionsbeing124months(95%CI:96.8-152.8)versus 23.3months for node-positive disease (95%CI:18.1-36.5). Increasing LNR was associated with decreased survival: LNR 0.01-0.2; 40.0months; LNR ≥0.2-0.4; 18.3months and LNR ≥0.4;10.1months.OnmultivariateanalysisLNstatus(Hazardratio4.6;95%CI2.6-9.6)and perineural invasion (Hazard ratio 3.3; 95%CI 1.5-7.3) maintained significance. Conclusion Positive LN status in ampullary adenocarcinoma is a strongly independent predictor of poor outcome.Pancreaticoduodenectomyiscurativein65%ofpatientswithnode-negativedisease. AmongsttheLNpositiveampullaryadenocarcinomaresectionsLNRwasinverselyassociated with outcome.","Source":"Google Scholar","category":"HUMAN","training_data":"The Prognostic Influence Of Lymph Node Ratio Following Pancreaticoduodenectomy For Ampullary Adenocarcinoma Background Survival after surgery for ampullary cancer remains poor. Prognostic factors including tumour stage, lymph node (LN) status, and tumour grade have been identified. Described as the lymph node ratio (LNR), the number of involved LNs compared to the numberexaminedhasbeenprognosticinpancreaticadenocarcinoma.Wesoughttoassessthe prognostic value of LNR on a consecutive series of ampullary adenocarcinomas undergoing pancreaticoduodenectomy.MethodsRetrospectivereviewofaprospectivedatabaseofpancreaticoduodenectomiesperformedbetween1997and2008wasundertaken.Clinicopathologic data was collected and the LNR calculated. Patients with positive LN status were grouped into: (1) LNR=0; (2) LNR 0.01-0.2; (3) LNR ≥0.2-0.4 and (4) LNR ≥0.4. Pa Survival outcome was compared using Kaplar-Meier/Cox proportional hazards analysis. Results 95 ampullary adenocarcinomas were identified with a median survival for the cohort being 31.2months (95%CI:18.2-67.4). The median number of LNs harvested was 20.0 (95%CI:18.5-22.1). LN involvement was associated with other aggressive tumour characteristicsincludinglymphovascularinvasion,tumourstageandnotablyanelevatedpre-operative C-reactiveproteinconcentration(p<0.05).OverallLNstatusinfluencedsurvivalwithmedian survivalforthe38(44.7%)negativeresectionsbeing124months(95%CI:96.8-152.8)versus 23.3months for node-positive disease (95%CI:18.1-36.5). Increasing LNR was associated with decreased survival: LNR 0.01-0.2; 40.0months; LNR ≥0.2-0.4; 18.3months and LNR ≥0.4;10.1months.OnmultivariateanalysisLNstatus(Hazardratio4.6;95%CI2.6-9.6)and perineural invasion (Hazard ratio 3.3; 95%CI 1.5-7.3) maintained significance. Conclusion Positive LN status in ampullary adenocarcinoma is a strongly independent predictor of poor outcome.Pancreaticoduodenectomyiscurativein65%ofpatientswithnode-negativedisease. AmongsttheLNpositiveampullaryadenocarcinomaresectionsLNRwasinverselyassociated with outcome. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"differences prevalence cancer stem cells features intrahepatic versus ductal cholangiocarcinoma cell lines background based anatomical location cholan giocarcinoma cca classified either intrahepatic icc ductular dcc iccs tend mass forming invasive recurrent metastasize whereas dccs grow locally diagnosed early cured surgical resection tumors tend resistant chemo therapy self renewal tumor formation invasiveness metastasis resistance chemotherapy plasticity features ascribed cancer stem cell csc population tumors purpose study determine prevalence features cscs differ icc versus dcc human cca cells lines methods cscs identified expression cd133 cd13 cd24 cd44 surface markers human hucct1 intra hepatic kmbc ductular cca cell lines vitro csc features included self renewal maintenance surface markers spheroid formation anchor free media tumor formation colony formation soft agar migra tion wound healing assay sensitivity chemotherapy wst 1 assay plasticity response hepatocyte inducing agents bmp 4 dexamethasone results four csc markers expressed 90 100 hucct1 cells continued expressed 30 days culture whereas expression negligible 5 kmbc cells hucct1 cells generated spheroids anchor free media kmbc cells cell populations formed colonies soft agar significantly colonies derived hucct1 cells p 0 05 hucct1 cells migrated wound healing assays greater extent kmbc cells p 0 05 hucct1 cells also resistant gemcitabine compared kmbc cells cell lines equally resistant fluorouracil pharmacolog ical concentrations finally cholangiocyte markers ck19 integrin expression significantly regu lated hucct1 kmbc cells following exposure bmp 4 dexamethasone conclusions based findings cscs may prevalent icc versus dcc tumors moreover icc cells demonstrate increased self re newal tumorigenesis invasiveness chemoresistance plasticity compared dcc cells thus differences prevalence cscs cell features may contribute observed differences icc dcc tumor biology google scholar","probabilities":0.9467213,"Title":"Differences In The Prevalence Of Cancer Stem Cells And Features Of Intrahepatic Versus Ductal Cholangiocarcinoma Cell Lines","Abstract":"Background: Based on their anatomical location, cholan-giocarcinoma (CCA) can be classified as either intrahepatic (ICC) or ductular (DCC). ICCs tend to be mass forming, invasive, recurrent and metastasize whereas DCCs grow locally and if diagnosed early, can be cured by surgical resection. Both tumors tend to be resistant to chemo-therapy. Self-renewal, tumor formation, invasiveness, metastasis, resistance to chemotherapy and plasticity are features that have been ascribed to the cancer stem cell (CSC) population of tumors. The purpose of this study was to determine if the prevalence and features of CSCs differ in ICC versus DCC human CCA cells lines. Methods: CSCs were identified by the expression of CD133, CD13, CD24 and CD44 surface markers on human HuCCT1 (intra-hepatic) and KMBC (ductular) CCA cell lines. In vitro CSC features included self-renewal (maintenance of surface markers and spheroid formation in anchor-free media), tumor formation (colony formation in soft agar), migra-tion (wound healing assay), sensitivity to chemotherapy (WST-1 assay) and plasticity (response to the hepatocyte inducing agents; BMP-4 and dexamethasone). Results: All four CSC markers were expressed in 90%-100% of HuCCT1 cells and continued to be expressed over 30 days of culture whereas expression was negligible (<5%) in KMBC cells. HuCCT1 cells generated spheroids in anchor-free media but KMBC cells did not. Both cell populations formed colonies in soft agar but significantly more colonies were derived from HuCCT1 cells (p<0.05). HuCCT1 cells migrated in wound healing assays to a greater extent than KMBC cells (p<0.05). HuCCT1 cells were also more resistant to gemcitabine compared to KMBC cells and both cell lines were equally resistant to fluorouracil in pharmacolog-ical concentrations. Finally, cholangiocyte markers CK19 and β-integrin expression were significantly down regu-lated in HuCCT1 but not KMBC cells following exposure to BMP-4/dexamethasone. Conclusions: Based on these findings, CSCs may be more prevalent in ICC versus DCC tumors. Moreover, ICC cells demonstrate increased self-re-newal, tumorigenesis, invasiveness, chemoresistance and plasticity compared to DCC cells. Thus, differences in the prevalence of CSCs and cell features may contribute to the observed differences in ICC and DCC tumor biology.","Source":"Google Scholar","category":"ANIMAL","training_data":"Differences In The Prevalence Of Cancer Stem Cells And Features Of Intrahepatic Versus Ductal Cholangiocarcinoma Cell Lines Background: Based on their anatomical location, cholan-giocarcinoma (CCA) can be classified as either intrahepatic (ICC) or ductular (DCC). ICCs tend to be mass forming, invasive, recurrent and metastasize whereas DCCs grow locally and if diagnosed early, can be cured by surgical resection. Both tumors tend to be resistant to chemo-therapy. Self-renewal, tumor formation, invasiveness, metastasis, resistance to chemotherapy and plasticity are features that have been ascribed to the cancer stem cell (CSC) population of tumors. The purpose of this study was to determine if the prevalence and features of CSCs differ in ICC versus DCC human CCA cells lines. Methods: CSCs were identified by the expression of CD133, CD13, CD24 and CD44 surface markers on human HuCCT1 (intra-hepatic) and KMBC (ductular) CCA cell lines. In vitro CSC features included self-renewal (maintenance of surface markers and spheroid formation in anchor-free media), tumor formation (colony formation in soft agar), migra-tion (wound healing assay), sensitivity to chemotherapy (WST-1 assay) and plasticity (response to the hepatocyte inducing agents; BMP-4 and dexamethasone). Results: All four CSC markers were expressed in 90%-100% of HuCCT1 cells and continued to be expressed over 30 days of culture whereas expression was negligible (<5%) in KMBC cells. HuCCT1 cells generated spheroids in anchor-free media but KMBC cells did not. Both cell populations formed colonies in soft agar but significantly more colonies were derived from HuCCT1 cells (p<0.05). HuCCT1 cells migrated in wound healing assays to a greater extent than KMBC cells (p<0.05). HuCCT1 cells were also more resistant to gemcitabine compared to KMBC cells and both cell lines were equally resistant to fluorouracil in pharmacolog-ical concentrations. Finally, cholangiocyte markers CK19 and β-integrin expression were significantly down regu-lated in HuCCT1 but not KMBC cells following exposure to BMP-4/dexamethasone. Conclusions: Based on these findings, CSCs may be more prevalent in ICC versus DCC tumors. Moreover, ICC cells demonstrate increased self-re-newal, tumorigenesis, invasiveness, chemoresistance and plasticity compared to DCC cells. Thus, differences in the prevalence of CSCs and cell features may contribute to the observed differences in ICC and DCC tumor biology. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"initial laparoscopic cholecystectomy influence outcomes definitive oncologic resection gallbladder cancer nan pubmed","probabilities":0.9799733,"Title":"Does initial laparoscopic cholecystectomy influence the outcomes of definitive oncologic resection for gallbladder cancer?","Abstract":"NaN","Source":"PubMed","category":"HUMAN","training_data":"Does initial laparoscopic cholecystectomy influence the outcomes of definitive oncologic resection for gallbladder cancer? nan PubMed","prediction_labels":"HUMAN"},{"cleaned":"routine histopathology carcinoma cholecystectomy specimens evidence based systematic review background routine histopathological examination gallbladder specimens mainly performed identify unexpected gallbladder carcinoma gbc systematic review assesses prevalence characteristics gbc cholecystectomy specimens methods pubmed embase web science cochrane library searched articles reporting finding gbc cholecystectomy specimens results 30 articles included 20 europe united states 10 asian origin western studies 276 cases gbc found 61 542 specimens median prevalence 0 4 95 confidence interval ci 0 3 0 6 65 expected pre intraoperatively asian studies 344 cases gbc found 37 365 specimens median prevalence 1 2 95 ci 0 8 1 7 45 expected pre intraoperatively subgroup analysis identification previously unexpected gbc affected treatment minority patients total 72 patients received treatment 32 patients 22 received secondary surgery 15 patients survived least 1 year conclusions histopathological finding gbc cholecystectomy appears rare event prevalence unexpected gbc higher asian studies western studies pre intraoperative sensitivity carcinoma low moreover diagnosis gbc time histopathology usually inconsequential results systematic review support routine histopathology cholecystectomy specimens clinical practice pubmed","probabilities":0.9799733,"Title":"Routine histopathology for carcinoma in cholecystectomy specimens not evidence based: a systematic review","Abstract":"BACKGROUND: Routine histopathological examination of gallbladder specimens is mainly performed to identify unexpected gallbladder carcinoma (GBC). This systematic review assesses the prevalence and characteristics of GBC in cholecystectomy specimens. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for all articles reporting on the finding of GBC in cholecystectomy specimens. RESULTS: Of the 30 articles included, 20 were from Europe and the United States, and 10 were of Asian origin. In the Western studies, 276 cases of GBC were found in 61,542 specimens (median prevalence 0.4%, 95% confidence interval [CI] 0.3-0.6). Of these, 65% were expected pre- or intraoperatively. In the Asian studies, 344 cases of GBC were found in 37,365 specimens (median prevalence 1.2%, 95% CI 0.8-1.7). Of these, 45% were expected pre- or intraoperatively. In a subgroup analysis, identification of previously unexpected GBC affected treatment in only a minority of patients. In total, 72% of the patients received no further treatment and 32 patients (22%) received secondary surgery, of whom 15 patients survived at least 1 year. CONCLUSIONS: The histopathological finding of GBC after cholecystectomy appears to be a rare event. The prevalence of unexpected GBC was higher in Asian studies than in Western studies. The pre- and intraoperative sensitivity for this carcinoma is low. Moreover, the diagnosis of GBC at the time of histopathology is usually inconsequential. The results of this systematic review do not support routine histopathology of cholecystectomy specimens in clinical practice.","Source":"PubMed","category":"HUMAN","training_data":"Routine histopathology for carcinoma in cholecystectomy specimens not evidence based: a systematic review BACKGROUND: Routine histopathological examination of gallbladder specimens is mainly performed to identify unexpected gallbladder carcinoma (GBC). This systematic review assesses the prevalence and characteristics of GBC in cholecystectomy specimens. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched for all articles reporting on the finding of GBC in cholecystectomy specimens. RESULTS: Of the 30 articles included, 20 were from Europe and the United States, and 10 were of Asian origin. In the Western studies, 276 cases of GBC were found in 61,542 specimens (median prevalence 0.4%, 95% confidence interval [CI] 0.3-0.6). Of these, 65% were expected pre- or intraoperatively. In the Asian studies, 344 cases of GBC were found in 37,365 specimens (median prevalence 1.2%, 95% CI 0.8-1.7). Of these, 45% were expected pre- or intraoperatively. In a subgroup analysis, identification of previously unexpected GBC affected treatment in only a minority of patients. In total, 72% of the patients received no further treatment and 32 patients (22%) received secondary surgery, of whom 15 patients survived at least 1 year. CONCLUSIONS: The histopathological finding of GBC after cholecystectomy appears to be a rare event. The prevalence of unexpected GBC was higher in Asian studies than in Western studies. The pre- and intraoperative sensitivity for this carcinoma is low. Moreover, the diagnosis of GBC at the time of histopathology is usually inconsequential. The results of this systematic review do not support routine histopathology of cholecystectomy specimens in clinical practice. PubMed","prediction_labels":"HUMAN"},{"cleaned":"peritumoral sparc expression patient outcome resectable intrahepatic cholangiocarcinoma background objectives cholangiocarcinoma cca affects thousands worldwide increasing incidence sparc secreted protein acidic rich cysteine plays important role cellular matrix interactions wound repair cellular migration reported prevent malignancy growth sparc undergoes epigenetic silencing pancreatic malignancy frequently expressed stromal fibroblasts adjacent infiltrating pancreatic adenocarcinomas cca also desmoplastic tumor similar pancreatic adenocarcinoma sparc clinical influence clinicopathological characteristics mass forming mf cca still remains unclear study evaluate expression sparc tumor stromal tissue clarity relation prognosis methods seventy eight mf cca patients underwent hepatectomy curative intent enrolled immunohistochemical study sparc expression immunostaining sparc characterized tumor stromal tissues conducted survival analysis 16 clinicopathological variables overall survival os analyzed kaplan meier analysis cox proportional hazards regression modeling results thirty three men 45 women mf cca studied within total 78 subjects 12 15 4 classified tumor negative stroma negative 37 47 4 tumor positive stroma negative four 5 1 tumor negative stroma positive 25 32 1 tumor positive stroma positive median follow 13 6 months 5 year os 14 9 cox proportional hazard analysis revealed sparc tumor positive stromal negative immunostaining curative hepatectomy predicted favorable os patients mf cca hepatectomy conclusion mf cca patients sparc tumor positive stromal negative expression may favorable os rates curative hepatectomy stn","probabilities":0.88235295,"Title":"Peritumoral Sparc Expression And Patient Outcome With Resectable Intrahepatic Cholangiocarcinoma","Abstract":"Background and objectives: Cholangiocarcinoma (CCA) affects thousands worldwide with increasing incidence. SPARC (secreted protein acidic and rich in cysteine) plays an important role in cellular matrix interactions, wound repair, and cellular migration, and has been reported to prevent malignancy from growth. SPARC undergoes epigenetic silencing in pancreatic malignancy, but is frequently expressed by stromal fibroblasts adjacent to infiltrating pancreatic adenocarcinomas. CCA is also a desmoplastic tumor, similar to pancreatic adenocarcinoma. SPARC's clinical influence on clinicopathological characteristics of mass-forming (MF)-CCA still remains unclear. In this study, we evaluate the expression of SPARC in tumor and stromal tissue to clarity its relation with prognosis. \r\n\r\n Methods: Seventy-eight MF-CCA patients who underwent hepatectomy with curative intent were enrolled for an immunohistochemical study of SPARC. The expression of immunostaining of SPARC was characterized for both tumor and stromal tissues. We conducted survival analysis with 16 clinicopathological variables. The overall survival (OS) was analyzed by Kaplan-Meier analysis and Cox proportional hazards regression modeling. \r\n\r\n Results: Thirty-three men and 45 women with MF-CCA were studied. Within total 78 subjects, 12 (15.4%) were classified as tumor negative/stroma negative, 37 (47.4%) as tumor positive/stroma negative, four (5.1%) as tumor negative/stroma positive, and 25 (32.1%) as tumor positive/stroma positive. With a median follow-up of 13.6 months, the 5-year OS was 14.9%. Cox proportional hazard analysis revealed that SPARC tumor positive and stromal negative immunostaining and curative hepatectomy predicted favorable OS in patients with MF-CCA after hepatectomy. \r\n\r\n Conclusion: MF-CCA patients with SPARC tumor positive and stromal negative expression may have favorable OS rates after curative hepatectomy.","Source":"STN","category":"HUMAN","training_data":"Peritumoral Sparc Expression And Patient Outcome With Resectable Intrahepatic Cholangiocarcinoma Background and objectives: Cholangiocarcinoma (CCA) affects thousands worldwide with increasing incidence. SPARC (secreted protein acidic and rich in cysteine) plays an important role in cellular matrix interactions, wound repair, and cellular migration, and has been reported to prevent malignancy from growth. SPARC undergoes epigenetic silencing in pancreatic malignancy, but is frequently expressed by stromal fibroblasts adjacent to infiltrating pancreatic adenocarcinomas. CCA is also a desmoplastic tumor, similar to pancreatic adenocarcinoma. SPARC's clinical influence on clinicopathological characteristics of mass-forming (MF)-CCA still remains unclear. In this study, we evaluate the expression of SPARC in tumor and stromal tissue to clarity its relation with prognosis. \r\n\r\n Methods: Seventy-eight MF-CCA patients who underwent hepatectomy with curative intent were enrolled for an immunohistochemical study of SPARC. The expression of immunostaining of SPARC was characterized for both tumor and stromal tissues. We conducted survival analysis with 16 clinicopathological variables. The overall survival (OS) was analyzed by Kaplan-Meier analysis and Cox proportional hazards regression modeling. \r\n\r\n Results: Thirty-three men and 45 women with MF-CCA were studied. Within total 78 subjects, 12 (15.4%) were classified as tumor negative/stroma negative, 37 (47.4%) as tumor positive/stroma negative, four (5.1%) as tumor negative/stroma positive, and 25 (32.1%) as tumor positive/stroma positive. With a median follow-up of 13.6 months, the 5-year OS was 14.9%. Cox proportional hazard analysis revealed that SPARC tumor positive and stromal negative immunostaining and curative hepatectomy predicted favorable OS in patients with MF-CCA after hepatectomy. \r\n\r\n Conclusion: MF-CCA patients with SPARC tumor positive and stromal negative expression may have favorable OS rates after curative hepatectomy. STN","prediction_labels":"HUMAN"},{"cleaned":"cancer mortality meat delicatessen departments supermarkets 1950 2006 meat cutters meat wrappers meat department supermarkets exposed oncogenic viruses present raw meat cattle pigs sheep poultry products unpasteurized milk raw eggs mid 1970s meat wrappers also exposed carcinogens present fumes emitted machine used wrap meat studied cancer mortality cohort 10 701 workers meat delicatessen departments supermarkets report findings third follow standardized mortality ratios smr estimated cohort whole race sex subgroups using us population comparison study subjects followed january 1950 december 2006 significantly increased smrs 1 3 95 ci 1 2 1 5 2 7 95 ci 1 2 5 3 recorded cancers lung tonsils oropharynx respectively entire cohort affecting nearly race sex subgroups smrs 4 6 95 ci 1 0 13 6 cancer floor mouth 2 8 95 ci 1 3 5 3 cancer gall bladder biliary tract recorded white male meatcutters significantly decreased smrs observed cancers known observed excess cancers result occupational exposures however substantial evidence points fumes wrapping machine possible candidate explaining excess female meat wrappers nested case control studies examine risks occupational exposures greater detail adequately control confounding factors needed permit specifically investigate role oncogenic viruses fumes non occupational risk factors occurrence cancers findings important occupationally also general population may also experience exposures albeit lesser degree pubmed","probabilities":0.9799733,"Title":"Cancer mortality in the meat and delicatessen departments of supermarkets (1950-2006)","Abstract":"Meat cutters and meat wrappers in the meat department of supermarkets are exposed to oncogenic viruses present in raw meat from cattle, pigs, sheep, and poultry, and their products (unpasteurized milk and raw eggs). Up to the mid 1970s, meat wrappers were also exposed to carcinogens present in fumes emitted from the machine used to wrap meat. Because of this we studied cancer mortality in a cohort of 10,701 workers in the meat and delicatessen departments of supermarkets, and we report here the findings after the third follow-up. Standardized mortality ratios (SMR) were estimated in the cohort as a whole and in race/sex subgroups, using the US population for comparison. Study subjects were followed up from January 1950 to December 2006. Significantly increased SMRs of 1.3 (95% CI, 1.2-1.5), and 2.7 (95% CI, 1.2-5.3) were recorded for cancers of the lung, and tonsils/oropharynx, respectively, in the entire cohort, affecting nearly all race/sex subgroups. SMRs of 4.6 (95% CI, 1.0-13.6) for cancer of the floor of the mouth, and 2.8 (95% CI, 1.3-5.3) for cancer of the gall bladder and biliary tract were recorded only in White male meatcutters. Significantly decreased SMRs were observed for a few cancers. It is not known if the observed excess of cancers is a result of occupational exposures. However, substantial evidence points to fumes from the wrapping machine as a possible candidate for explaining the excess in female meat wrappers. Nested case-control studies that can examine risks from occupational exposures in greater detail, and adequately control for confounding factors are now needed, to permit specifically investigate the role of the oncogenic viruses, fumes and non-occupational risk factors in the occurrence of these cancers. The findings are important, not only occupationally but also because the general population may also experience these exposures, albeit to a lesser degree.","Source":"PubMed","category":"HUMAN","training_data":"Cancer mortality in the meat and delicatessen departments of supermarkets (1950-2006) Meat cutters and meat wrappers in the meat department of supermarkets are exposed to oncogenic viruses present in raw meat from cattle, pigs, sheep, and poultry, and their products (unpasteurized milk and raw eggs). Up to the mid 1970s, meat wrappers were also exposed to carcinogens present in fumes emitted from the machine used to wrap meat. Because of this we studied cancer mortality in a cohort of 10,701 workers in the meat and delicatessen departments of supermarkets, and we report here the findings after the third follow-up. Standardized mortality ratios (SMR) were estimated in the cohort as a whole and in race/sex subgroups, using the US population for comparison. Study subjects were followed up from January 1950 to December 2006. Significantly increased SMRs of 1.3 (95% CI, 1.2-1.5), and 2.7 (95% CI, 1.2-5.3) were recorded for cancers of the lung, and tonsils/oropharynx, respectively, in the entire cohort, affecting nearly all race/sex subgroups. SMRs of 4.6 (95% CI, 1.0-13.6) for cancer of the floor of the mouth, and 2.8 (95% CI, 1.3-5.3) for cancer of the gall bladder and biliary tract were recorded only in White male meatcutters. Significantly decreased SMRs were observed for a few cancers. It is not known if the observed excess of cancers is a result of occupational exposures. However, substantial evidence points to fumes from the wrapping machine as a possible candidate for explaining the excess in female meat wrappers. Nested case-control studies that can examine risks from occupational exposures in greater detail, and adequately control for confounding factors are now needed, to permit specifically investigate the role of the oncogenic viruses, fumes and non-occupational risk factors in the occurrence of these cancers. The findings are important, not only occupationally but also because the general population may also experience these exposures, albeit to a lesser degree. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cytokeratin 20 ck20 apomucin 1 muc1 expression ampullary carcinoma correlation tumor progression prognosis background assessed expression cytokeratin ck apomucin muc ampullary carcinoma ac develop system classification acs basis clinical significance method studied expressions ck7 ck20 muc1 muc2 muc5ac muc6 43 patients acs clinical data obtained retrospectively examining surgically resected acs patients results classified cases 3 groups tumors expressing ck20 lacking muc1 intestinal type type 26 tumors expressing muc1 lacking ck20 pancreatobiliary type pb type 35 expressing lacking ck20 muc1 type o type 39 eight 73 11 type carcinomas 3 20 15 pb type carcinomas 4 24 17 o type carcinomas classified pt1 number type carcinomas early tumor stages significantly higher number pb o type carcinomas p 0 014 p 0 018 respectively 5 year survival rates pt1 pt2 pt3 tumors 76 33 22 respectively p 0 001 rates muc5ac muc6 coexpression type pb type o type tumors 18 13 53 respectively significant correlation muc5ac muc6 coexpression o type characteristics p 0 031 five year survival rates o type acs without muc5ac muc6 coexpression 71 17 respectively p 0 048 conclusions immunohistochemical subtypes based ck muc expression correlated tumor progression gastric muc5ac muc6 coexpression correlated better prognosis o type acs pubmed","probabilities":0.9799733,"Title":"Cytokeratin 20 (CK20) and apomucin 1 (MUC1) expression in ampullary carcinoma: Correlation with tumor progression and prognosis","Abstract":"BACKGROUND: We assessed the expression of cytokeratin (CK) and apomucin (MUC) in ampullary carcinoma (AC) to develop a system for the classification of ACs on the basis of their clinical significance. METHOD: We studied the expressions of CK7, CK20, MUC1, MUC2, MUC5AC, and MUC6 in 43 patients with ACs. Clinical data were obtained retrospectively by examining surgically resected ACs of the patients. RESULTS: We classified the cases into 3 groups: tumors expressing CK20 and lacking MUC1 (intestinal type [I-type], 26%), tumors expressing MUC1 and lacking CK20 (pancreatobiliary type [PB-type], 35%), and those expressing or lacking both CK20 and MUC1 (other type [O-type], 39%). Eight (73%) of 11 I-type carcinomas, 3 (20%) of 15 PB-type carcinomas, and 4 (24%) of 17 O-type carcinomas were classified as pT1. The number of I-type carcinomas in the early tumor stages was significantly higher than the number of PB- and O-type carcinomas (p = 0.014 and p = 0.018, respectively). The 5-year survival rates for pT1, pT2, and pT3 tumors were 76%, 33%, and 22%, respectively (p < 0.001). Rates of MUC5AC and MUC6 coexpression for I-type, PB-type, and O-type tumors were 18%, 13%, and 53%, respectively. There was a significant correlation between MUC5AC and MUC6 coexpression and O-type characteristics (p = 0.031). The five-year survival rates for O-type ACs with and without MUC5AC and MUC6 coexpression were 71% and 17%, respectively (p = 0.048). CONCLUSIONS: The immunohistochemical subtypes based on CK and MUC expression correlated with tumor progression. Gastric MUC5AC and MUC6 coexpression correlated with better prognosis for O-type ACs.","Source":"PubMed","category":"HUMAN","training_data":"Cytokeratin 20 (CK20) and apomucin 1 (MUC1) expression in ampullary carcinoma: Correlation with tumor progression and prognosis BACKGROUND: We assessed the expression of cytokeratin (CK) and apomucin (MUC) in ampullary carcinoma (AC) to develop a system for the classification of ACs on the basis of their clinical significance. METHOD: We studied the expressions of CK7, CK20, MUC1, MUC2, MUC5AC, and MUC6 in 43 patients with ACs. Clinical data were obtained retrospectively by examining surgically resected ACs of the patients. RESULTS: We classified the cases into 3 groups: tumors expressing CK20 and lacking MUC1 (intestinal type [I-type], 26%), tumors expressing MUC1 and lacking CK20 (pancreatobiliary type [PB-type], 35%), and those expressing or lacking both CK20 and MUC1 (other type [O-type], 39%). Eight (73%) of 11 I-type carcinomas, 3 (20%) of 15 PB-type carcinomas, and 4 (24%) of 17 O-type carcinomas were classified as pT1. The number of I-type carcinomas in the early tumor stages was significantly higher than the number of PB- and O-type carcinomas (p = 0.014 and p = 0.018, respectively). The 5-year survival rates for pT1, pT2, and pT3 tumors were 76%, 33%, and 22%, respectively (p < 0.001). Rates of MUC5AC and MUC6 coexpression for I-type, PB-type, and O-type tumors were 18%, 13%, and 53%, respectively. There was a significant correlation between MUC5AC and MUC6 coexpression and O-type characteristics (p = 0.031). The five-year survival rates for O-type ACs with and without MUC5AC and MUC6 coexpression were 71% and 17%, respectively (p = 0.048). CONCLUSIONS: The immunohistochemical subtypes based on CK and MUC expression correlated with tumor progression. Gastric MUC5AC and MUC6 coexpression correlated with better prognosis for O-type ACs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer involving extrahepatic bile duct worthy resection objective clarify value resection gallbladder cancer involving extrahepatic bile duct background several recent studies proven jaundice extrahepatic biliary involvement independent predictors poor outcome authors recommend resection advanced disease methods one hundred patients pt3 4 pn0 1 m0 disease subjects study mortality long term outcome analyzed using prospectively collected database results factor associated mortality univariate multivariate analyses intraoperative blood loss 5 year survival rate median survival time 23 1 5 years patients pathologic extrahepatic biliary invasion pebi 54 15 4 years patients without pebi twelve patients pebi survived beyond 5 years multivariate analysis revealed r1 2 resection combined resection adjacent organs liver extrahepatic bile duct crao independent predictors poor outcome five year survival rate median survival time r0 resection without crao 36 3 8 years even patients pebi contrast r0 resection crao 5 year survival median survival time 16 0 8 years respectively conclusions patients advanced gallbladder cancer pebi candidates resection distant metastases absent r0 resection achievable crao unnecessary surgical resection aggressively planned pubmed","probabilities":0.9799733,"Title":"Gallbladder cancer involving the extrahepatic bile duct is worthy of resection","Abstract":"OBJECTIVE: To clarify the value of resection of gallbladder cancer involving the extrahepatic bile duct. BACKGROUND: : Several recent studies have proven that jaundice and extrahepatic biliary involvement are independent predictors of a poor outcome. Only a few authors recommend resection of such advanced disease. METHODS: One hundred patients with pT3/4, pN0/1, M0 disease were the subjects of this study. Mortality and long-term outcome were analyzed using a prospectively collected database. RESULTS: The only factor associated with mortality in univariate and multivariate analyses was intraoperative blood loss. The 5-year survival rate and median survival time were 23% and 1.5 years for patients with pathologic extrahepatic biliary invasion (pEBI), and 54% and 15.4 years for patients without pEBI. Twelve patients with pEBI survived beyond 5 years. Multivariate analysis revealed that R1/2 resection and combined resection of adjacent organs other than the liver and extrahepatic bile duct (CRAO) were independent predictors of poor outcome. Five-year survival rate and median survival time after R0 resection without CRAO were 36% and 3.8 years even in patients with pEBI. In contrast, after R0 resection with CRAO 5-year survival and median survival time were 16% and 0.8 years, respectively. CONCLUSIONS: Patients with advanced gallbladder cancer with pEBI are candidates for resection when distant metastases are absent and R0 resection is achievable. When CRAO is unnecessary, surgical resection should be aggressively planned.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder cancer involving the extrahepatic bile duct is worthy of resection OBJECTIVE: To clarify the value of resection of gallbladder cancer involving the extrahepatic bile duct. BACKGROUND: : Several recent studies have proven that jaundice and extrahepatic biliary involvement are independent predictors of a poor outcome. Only a few authors recommend resection of such advanced disease. METHODS: One hundred patients with pT3/4, pN0/1, M0 disease were the subjects of this study. Mortality and long-term outcome were analyzed using a prospectively collected database. RESULTS: The only factor associated with mortality in univariate and multivariate analyses was intraoperative blood loss. The 5-year survival rate and median survival time were 23% and 1.5 years for patients with pathologic extrahepatic biliary invasion (pEBI), and 54% and 15.4 years for patients without pEBI. Twelve patients with pEBI survived beyond 5 years. Multivariate analysis revealed that R1/2 resection and combined resection of adjacent organs other than the liver and extrahepatic bile duct (CRAO) were independent predictors of poor outcome. Five-year survival rate and median survival time after R0 resection without CRAO were 36% and 3.8 years even in patients with pEBI. In contrast, after R0 resection with CRAO 5-year survival and median survival time were 16% and 0.8 years, respectively. CONCLUSIONS: Patients with advanced gallbladder cancer with pEBI are candidates for resection when distant metastases are absent and R0 resection is achievable. When CRAO is unnecessary, surgical resection should be aggressively planned. PubMed","prediction_labels":"HUMAN"},{"cleaned":"postoperative external irradiation patients primary biliary tract cancer multicenter retrospective study background aim aim present study assess clinical outcomes postoperative radiotherapy biliary tract cancer patients patients methods clinical results 187 patients treated external irradiation 31 japanese institutions 2000 2011 retrospectively analyzed median radiation dose 50 4 gy fractions 1 8 2 gy results two year actuarial overall survival locoregional control lcs rates 56 68 respectively multivariate analysis macroscopic residual tumor r2 irradiated doses 54 gy significant indicators poor lc prognosis patients complete resection r0 microscopic residual tumor r1 2 year lcs 71 54 gy 83 54 gy doses 54 gy associated high long term lcs significant difference acute adverse event rates 54 gy 54 gy conclusion postoperative irradiation doses approximately 54 gy safe effective r0 r1 resection patients pubmed","probabilities":0.9799733,"Title":"Postoperative External Irradiation of Patients with Primary Biliary Tract Cancer: A Multicenter Retrospective Study","Abstract":"BACKGROUND/AIM: The aim of the present study was to assess clinical outcomes of postoperative radiotherapy for biliary tract cancer patients. PATIENTS AND METHODS: Clinical results of 187 patients treated with external irradiation in 31 Japanese Institutions between 2000 and 2011 were retrospectively analyzed. The median radiation dose was 50.4 Gy in fractions of 1.8-2 Gy. RESULTS: Two-year actuarial overall survival and locoregional control (LCs) rates were 56% and 68%, respectively. In multivariate analysis, macroscopic residual tumor (R2) and irradiated doses <54 Gy were significant indicators of poor LC prognosis. For patients with complete resection (R0) or microscopic residual tumor (R1), 2-year LCs were 71% for <54 Gy and 83% for ≥54 Gy; doses ≥54 Gy were associated with high long-term LCs. There was no significant difference in acute adverse event rates between <54 Gy and ≥54 Gy. CONCLUSION: Postoperative irradiation doses of approximately 54 Gy are safe and effective for R0 or R1 resection patients.","Source":"PubMed","category":"HUMAN","training_data":"Postoperative External Irradiation of Patients with Primary Biliary Tract Cancer: A Multicenter Retrospective Study BACKGROUND/AIM: The aim of the present study was to assess clinical outcomes of postoperative radiotherapy for biliary tract cancer patients. PATIENTS AND METHODS: Clinical results of 187 patients treated with external irradiation in 31 Japanese Institutions between 2000 and 2011 were retrospectively analyzed. The median radiation dose was 50.4 Gy in fractions of 1.8-2 Gy. RESULTS: Two-year actuarial overall survival and locoregional control (LCs) rates were 56% and 68%, respectively. In multivariate analysis, macroscopic residual tumor (R2) and irradiated doses <54 Gy were significant indicators of poor LC prognosis. For patients with complete resection (R0) or microscopic residual tumor (R1), 2-year LCs were 71% for <54 Gy and 83% for ≥54 Gy; doses ≥54 Gy were associated with high long-term LCs. There was no significant difference in acute adverse event rates between <54 Gy and ≥54 Gy. CONCLUSION: Postoperative irradiation doses of approximately 54 Gy are safe and effective for R0 or R1 resection patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"safety feasibility enhanced recovery surgery patients underwent pancreaticoduodenectomy hepatobiliary pancreatic malignancy purpose study assessed whether enhanced recovery surgery eras program distal pancreatectomy dp safe feasible patients methods subjects patients underwent consecutive dp 2012 2014 department gastrointestinal surgery kanagawa cancer center received perioperative care according eras program data retrieved retrospectively outcome measures included postoperative mortality morbidity hospitalization 30 day readmission rate eras program included 12 elements 4 preoperative elements 3 intraoperative elements 5 postoperative elements results total 44 patients studied overall incidence morbidity 29 5 incidence mortality 0 incidence readmission 0 four preoperative elements 3 intraoperative elements seemed feasible among 5 postoperative elements 4 elements seemed feasible accounting 90 performance rate however early removal catheters drain seemed feasible median postoperative hospital stay 14 days range 8 39 days median postoperative hospital stay 13 days range 8 27 days patients without postoperative complications median postoperative hospital stay 26 days range 14 39 days patients postoperative complications conclusion study results suggested eras program safe feasible patients undergo dp however achieving compliance postoperative element especially removal catcher drain challenging google scholar","probabilities":0.9799733,"Title":"Safety And Feasibility Of Enhanced Recovery After Surgery In The Patients Underwent Pancreaticoduodenectomy For Hepatobiliary And Pancreatic Malignancy","Abstract":"Purpose: This study assessed whether our enhanced recovery after surgery (ERAS) program for distal pancreatectomy (DP) is safe and feasible.\nPatients and Methods: The subjects were patients who underwent consecutive DP between 2012 and 2014 at the Department of Gastrointestinal Surgery, Kanagawa Cancer Center. They received perioperative care according to ERAS program. All data were retrieved retrospectively. Outcome measures included postoperative mortality, morbidity, hospitalization, and 30-day readmission rate. Our ERAS program included 12 elements (4 preoperative elements, 3 intraoperative elements, and 5 postoperative elements).\nResults: A total of 44 patients were studied. The overall incidence of morbidity was 29.5%, the incidence of mortality was 0%, and the incidence of readmission was 0%. Four preoperative elements and 3 intraoperative elements seemed feasible. Among the 5 postoperative elements, 4 elements seemed feasible, accounting 90%< performance rate however the early removal of catheters and drain seemed not feasible. The median postoperative hospital stay was 14 days (range: 8–39 days). The median postoperative hospital stay was 13 days (range: 8–27 days) in patients without postoperative complications while the median postoperative hospital stay was 26 days (range: 14–39 days) in patients with postoperative complications.\nConclusion: This study results suggested that our ERAS program is safe and feasible in patients who undergo DP. However, achieving compliance on the postoperative element, especially the removal of catcher and drain, was more challenging.","Source":"Google Scholar","category":"HUMAN","training_data":"Safety And Feasibility Of Enhanced Recovery After Surgery In The Patients Underwent Pancreaticoduodenectomy For Hepatobiliary And Pancreatic Malignancy Purpose: This study assessed whether our enhanced recovery after surgery (ERAS) program for distal pancreatectomy (DP) is safe and feasible.\nPatients and Methods: The subjects were patients who underwent consecutive DP between 2012 and 2014 at the Department of Gastrointestinal Surgery, Kanagawa Cancer Center. They received perioperative care according to ERAS program. All data were retrieved retrospectively. Outcome measures included postoperative mortality, morbidity, hospitalization, and 30-day readmission rate. Our ERAS program included 12 elements (4 preoperative elements, 3 intraoperative elements, and 5 postoperative elements).\nResults: A total of 44 patients were studied. The overall incidence of morbidity was 29.5%, the incidence of mortality was 0%, and the incidence of readmission was 0%. Four preoperative elements and 3 intraoperative elements seemed feasible. Among the 5 postoperative elements, 4 elements seemed feasible, accounting 90%< performance rate however the early removal of catheters and drain seemed not feasible. The median postoperative hospital stay was 14 days (range: 8–39 days). The median postoperative hospital stay was 13 days (range: 8–27 days) in patients without postoperative complications while the median postoperative hospital stay was 26 days (range: 14–39 days) in patients with postoperative complications.\nConclusion: This study results suggested that our ERAS program is safe and feasible in patients who undergo DP. However, achieving compliance on the postoperative element, especially the removal of catcher and drain, was more challenging. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"mir 1 mir 145 act tumor suppressor micrornas gallbladder cancer development mirna based therapeutics represents new strategy cancer treatment objectives study evaluate differential expression micrornas gallbladder cancer gbc assess functional role mir 1 mir 145 gbc cell behavior profile mirna expression determined using dharmacontm microarray technology differential expression five micrornas validated taqman reverse transcription quantitative pcr separate cohort 8 tumors 3 non cancerous samples explored functional role mir 1 mir 145 tumor cell behavior ectopic vitro expression gbc noz cell line several mirnas found aberrantly expressed gbc showed significantly decreased expression compared non neoplastic tissues q value 0 05 differential expression 7 selected mirnas confirmed real time pcr pathway enrichment analysis revealed deregulated mirnas mir 1 mir 133 mir 143 mir 145 collectively targeted number genes belonging signaling pathways tgf erbb3 wnt vegf regulating cell motility adhesion ectopic expression mir 1 mir 145 noz cells significantly inhibited cell viability colony formation p 0 01 reduced gene expression vegf axl study represents first investigation mirna expression profile gallbladder cancer findings showed several mirnas deregulated neoplasm vitro functional assays suggest mir 1 mir 145 act tumor suppressor micrornas gbc pubmed","probabilities":0.962963,"Title":"miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer","Abstract":"The development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using DharmaconTM microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q value<0.05). The differential expression of 7 selected miRNAs was confirmed by real time PCR. Pathway enrichment analysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-β, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P<0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC.","Source":"PubMed","category":"ANIMAL","training_data":"miR-1 and miR-145 act as tumor suppressor microRNAs in gallbladder cancer The development of miRNA-based therapeutics represents a new strategy in cancer treatment. The objectives of this study were to evaluate the differential expression of microRNAs in gallbladder cancer (GBC) and to assess the functional role of miR-1 and miR-145 in GBC cell behavior. A profile of miRNA expression was determined using DharmaconTM microarray technology. Differential expression of five microRNAs was validated by TaqMan reverse transcription quantitative-PCR in a separate cohort of 8 tumors and 3 non-cancerous samples. Then, we explored the functional role of miR-1 and miR-145 in tumor cell behavior by ectopic in vitro expression in the GBC NOZ cell line. Several miRNAs were found to be aberrantly expressed in GBC; most of these showed a significantly decreased expression compared to non-neoplastic tissues (Q value<0.05). The differential expression of 7 selected miRNAs was confirmed by real time PCR. Pathway enrichment analysis revealed that the most deregulated miRNAs (miR-1, miR-133, miR-143 and miR-145) collectively targeted a number of genes belonging to signaling pathways such as TGF-β, ErbB3, WNT and VEGF, and those regulating cell motility or adhesion. The ectopic expression of miR-1 and miR-145 in NOZ cells significantly inhibited cell viability and colony formation (P<0.01) and reduced gene expression of VEGF-A and AXL. This study represents the first investigation of the miRNA expression profile in gallbladder cancer, and our findings showed that several miRNAs are deregulated in this neoplasm. In vitro functional assays suggest that miR-1 and miR-145 act as tumor suppressor microRNAs in GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long non coding rna pvt1 promotes cell proliferation migration silencing angptl4 expression cholangiocarcinoma cholangiocarcinoma cca common biliary tract malignancy low survival rate limited treatment options long non coding rnas lncrnas recently verified significant regulatory functions many kinds human cancers discovered study lncrna pvt1 whose expression significantly elevated cca molecular marker cca experiments indicated pvt1 knockdown greatly inhibited cell migration proliferation vitro vivo according rna sequencing rna seq analysis pvt1 knockdown dramatically influenced target genes associated cell angiogenesis cell proliferation apoptotic process rna immunoprecipitation rip analysis demonstrated binding epigenetic modification complexes prc2 pvt1 adjust histone methylation promoter angptl4 angiopoietin like 4 thus promote cell growth migration apoptosis progression data verified significant functions pvt1 cca oncogenesis suggested pvt1 target cca intervention stn","probabilities":0.9467213,"Title":"Long Non-Coding Rna Pvt1 Promotes Cell Proliferation And Migration By Silencing Angptl4 Expression In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA sequencing (RNA-seq) analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation, and the apoptotic process. RNA immunoprecipitation (RIP) analysis demonstrated that, by binding to epigenetic modification complexes (PRC2), PVT1 could adjust the histone methylation of the promoter of ANGPTL4 (angiopoietin-like 4) and, thus, promote cell growth, migration, and apoptosis progression. The data verified the significant functions of PVT1 in CCA oncogenesis, and they suggested that PVT1 could be a target for CCA intervention.","Source":"STN","category":"ANIMAL","training_data":"Long Non-Coding Rna Pvt1 Promotes Cell Proliferation And Migration By Silencing Angptl4 Expression In Cholangiocarcinoma Cholangiocarcinoma (CCA) is the most common biliary tract malignancy, with a low survival rate and limited treatment options. Long non-coding RNAs (lncRNAs) have recently been verified to have significant regulatory functions in many kinds of human cancers. It was discovered in this study that the lncRNA PVT1, whose expression is significantly elevated in CCA, could be a molecular marker of CCA. Experiments indicated that PVT1 knockdown greatly inhibited cell migration and proliferation in vitro and in vivo. According to RNA sequencing (RNA-seq) analysis, PVT1 knockdown dramatically influenced target genes associated with cell angiogenesis, cell proliferation, and the apoptotic process. RNA immunoprecipitation (RIP) analysis demonstrated that, by binding to epigenetic modification complexes (PRC2), PVT1 could adjust the histone methylation of the promoter of ANGPTL4 (angiopoietin-like 4) and, thus, promote cell growth, migration, and apoptosis progression. The data verified the significant functions of PVT1 in CCA oncogenesis, and they suggested that PVT1 could be a target for CCA intervention. STN","prediction_labels":"ANIMAL"},{"cleaned":"survival outcomes prognostic factors surgical therapy potentially resectable intrahepatic cholangiocarcinoma large single center cohort study background surgical resection currently indicated potentially resectable intrahepatic cholangiocarcinoma icc survival outcomes prognostic factors well documented due rarity study aims assess large consecutive series patients icc treated surgically methods retrospective study conducted 1 333 icc patients undergoing surgery january 2007 december 2011 surgical results survival evaluated compared among different subgroups patients univariate multivariate analyses performed identify prognostic factors results r0 r1 r2 resection exploratory laparotomy obtained 34 8 44 9 16 4 3 9 patients respectively overall 1 3 5 year survival rates entire cohort 58 2 25 2 17 0 respectively corresponding rates 79 1 42 6 28 7 patients r0 resection 60 5 20 1 13 9 patients r1 resection 20 5 7 4 0 patients r2 resection 3 8 0 0 patients exploratory laparotomy independent factors poor survival included positive resection margin lymph node metastasis multiple tumors vascular invasion elevated ca19 9 cea whereas hepatitis b virus infection cirrhosis independently favorable prognosis indicators conclusions r0 resection offers best possibility long term survival chance r0 resection low surgery performed potential resectable icc randomized trials warranted refine indications surgery management icc pubmed","probabilities":0.9799733,"Title":"Survival outcomes and prognostic factors of surgical therapy for all potentially resectable intrahepatic cholangiocarcinoma: a large single-center cohort study","Abstract":"BACKGROUND: Surgical resection is currently indicated for all potentially resectable intrahepatic cholangiocarcinoma (ICC), but the survival outcomes and the prognostic factors have not been well-documented due to its rarity. This study aims to assess these in a large, consecutive series of patients with ICC treated surgically. METHODS: A retrospective study was conducted on 1,333 ICC patients undergoing surgery between January 2007 and December 2011. Surgical results and survival were evaluated and compared among different subgroups of patients. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: R0, R1, R2 resection and exploratory laparotomy were obtained in 34.8, 44.9, 16.4, and 3.9% of the patients, respectively. The overall 1-, 3-, and 5-year survival rates for the entire cohort were 58.2, 25.2, and 17.0%, respectively, with corresponding rates of 79.1, 42.6, and 28.7% for patients with R0 resection; 60.5, 20.1, and 13.9% for patients with R1 resection; 20.5, 7.4, and 0% for patients with R2 resection; and 3.8, 0, and 0% for patients with an exploratory laparotomy. Independent factors for poor survival included positive resection margin, lymph node metastasis, multiple tumors, vascular invasion, and elevated CA19-9 and/or CEA, whereas hepatitis B virus infection and cirrhosis were independently favorable prognosis indicators. CONCLUSIONS: R0 resection offers the best possibility of long-term survival, but the chance of a R0 resection is low when surgery is performed for potential resectable ICC. Further randomized trials are warranted to refine indications for surgery in the management of ICC.","Source":"PubMed","category":"HUMAN","training_data":"Survival outcomes and prognostic factors of surgical therapy for all potentially resectable intrahepatic cholangiocarcinoma: a large single-center cohort study BACKGROUND: Surgical resection is currently indicated for all potentially resectable intrahepatic cholangiocarcinoma (ICC), but the survival outcomes and the prognostic factors have not been well-documented due to its rarity. This study aims to assess these in a large, consecutive series of patients with ICC treated surgically. METHODS: A retrospective study was conducted on 1,333 ICC patients undergoing surgery between January 2007 and December 2011. Surgical results and survival were evaluated and compared among different subgroups of patients. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: R0, R1, R2 resection and exploratory laparotomy were obtained in 34.8, 44.9, 16.4, and 3.9% of the patients, respectively. The overall 1-, 3-, and 5-year survival rates for the entire cohort were 58.2, 25.2, and 17.0%, respectively, with corresponding rates of 79.1, 42.6, and 28.7% for patients with R0 resection; 60.5, 20.1, and 13.9% for patients with R1 resection; 20.5, 7.4, and 0% for patients with R2 resection; and 3.8, 0, and 0% for patients with an exploratory laparotomy. Independent factors for poor survival included positive resection margin, lymph node metastasis, multiple tumors, vascular invasion, and elevated CA19-9 and/or CEA, whereas hepatitis B virus infection and cirrhosis were independently favorable prognosis indicators. CONCLUSIONS: R0 resection offers the best possibility of long-term survival, but the chance of a R0 resection is low when surgery is performed for potential resectable ICC. Further randomized trials are warranted to refine indications for surgery in the management of ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental finding gallbladder carcinoma background carcinoma gallbladder fifth common gastrointestinal malignancy common biliary tract usually discovered accidentally gallbladder carcinoma diagnosed pathologically 0 3 1 5 cholecystectomy specimens aim objectives evaluate impact incidental gallbladder cancer surgical experience establish overall rate gallbladder carcinoma methods retrospectively evaluated consecutive cholecystectomies performed ward 2007 2012 order determine incidence gallbladder carcinoma identify common characteristics particular group patients results 580 cholecystectomies performed ward 2007 2012 gallbladder carcinoma diagnosed six patients 1 03 suspected prior surgery accordance literature occurrence women 4 6 higher men 2 6 mean age 64 years range 55 90 common symptom abdominal pain majority 5 6 cholelithiasis pathologic report confirmed diagnosis adenocarcinoma six patients conclusions overall incidence unsuspected gallbladder carcinoma series 1 03 find common characteristics particular group patients compared patients non malignant pathology google scholar","probabilities":0.9799733,"Title":"Incidental Finding Of Gallbladder Carcinoma","Abstract":"Background:\nCarcinoma of the gallbladder is the fifth most common gastrointestinal malignancy (and the most common of the biliary tract) and is usually discovered accidentally. Gallbladder carcinoma is diagnosed pathologically in 0.3-1.5% of cholecystectomy specimens.\nAIM and Objectives:\nTo evaluate the impact of incidental gallbladder cancer on surgical experience and to establish the overall rate of gallbladder carcinoma.\nMethods:\nWe retrospectively evaluated all consecutive cholecystectomies performed in our ward from (2007-2012) in order to Determine the incidence of gallbladder carcinoma and to identify common characteristics of this particular group of patients.\nResults:\nOf the 580 cholecystectomies performed in our ward from 2007-2012, gallbladder carcinoma was diagnosed in six patients (1.03%) but was not suspected prior to surgery in any of them. In accordance with the literature, the occurrence in women (4/6) was higher than in men (2/6). The mean age was 64 years (range 55-90).The most common symptom was abdominal pain; the majority (5/6) had cholelithiasis, and the pathologic report confirmed the diagnosis of adenocarcinoma in all six patients.\nConclusions:\nThe overall incidence of unsuspected gallbladder carcinoma in our series was 1.03%. We could not find any common characteristics for this particular group of patients when compared to patients with non-malignant pathology.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidental Finding Of Gallbladder Carcinoma Background:\nCarcinoma of the gallbladder is the fifth most common gastrointestinal malignancy (and the most common of the biliary tract) and is usually discovered accidentally. Gallbladder carcinoma is diagnosed pathologically in 0.3-1.5% of cholecystectomy specimens.\nAIM and Objectives:\nTo evaluate the impact of incidental gallbladder cancer on surgical experience and to establish the overall rate of gallbladder carcinoma.\nMethods:\nWe retrospectively evaluated all consecutive cholecystectomies performed in our ward from (2007-2012) in order to Determine the incidence of gallbladder carcinoma and to identify common characteristics of this particular group of patients.\nResults:\nOf the 580 cholecystectomies performed in our ward from 2007-2012, gallbladder carcinoma was diagnosed in six patients (1.03%) but was not suspected prior to surgery in any of them. In accordance with the literature, the occurrence in women (4/6) was higher than in men (2/6). The mean age was 64 years (range 55-90).The most common symptom was abdominal pain; the majority (5/6) had cholelithiasis, and the pathologic report confirmed the diagnosis of adenocarcinoma in all six patients.\nConclusions:\nThe overall incidence of unsuspected gallbladder carcinoma in our series was 1.03%. We could not find any common characteristics for this particular group of patients when compared to patients with non-malignant pathology. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"immune responses tumour associated antigen derived cytotoxic lymphocyte epitopes cholangiocarcinoma patients background aims immunotherapy promising treatment option cholangiocarcinoma compared cytotoxic lymphocyte ctl responses several tumour associated antigen taa derived epitopes cholangiocarcinoma patients identify candidate epitopes immunotherapy methods twenty six taas selected expression taas 6 cholangiocarcinoma cell lines 9 specimens measured using real time polymerase chain reaction pcr ctl responses 38 taa derived epitopes measured using samples 26 cholangiocarcinoma patients interferon enzyme linked immunospot elispot assay results taas expressed cholangiocarcinoma cell lines specimens pcr epitopes stimulated specific immune response defined elicited ctl response 3 patients little response healthy volunteers measured elispot assay based criteria 18 epitopes stimulated specific immune responses squamous cell carcinoma antigen recognized cells sart 1 690 p53 161 multidrug resistance associated protein mrp 3 503 survivin2b 80 melanoma associated antigen mage a4 143 receptor tyrosine kinase erbb 2 neu her2 neu 63 wilms tumour wt1 235 wt1 417 catenin 29 carcinoembryonic antigen cea 268 cea 652 epithelial cell adhesion molecule epcam 173 enhancer zeste homolog ezh 2 291 mucin 5ac muc5ac 716 glypican 3 gpc3 298 kinesin family member 20a kif20a 66 furthermore absolute number lymphocytes peripheral blood significantly correlated taa specific response lastly overall survival significantly prolonged patients 2 taa specific ctl responses compared none one conclusions results demonstrated several taas may promising immunotherapy cholangiocarcinoma patients high lymphocyte counts may benefit immunotherapy pubmed","probabilities":0.875,"Title":"Immune responses against tumour-associated antigen-derived cytotoxic T lymphocyte epitopes in cholangiocarcinoma patients","Abstract":"BACKGROUND & AIMS: Immunotherapy is a promising treatment option for cholangiocarcinoma. We compared cytotoxic T lymphocyte (CTL) responses against several tumour-associated antigen (TAA)-derived epitopes in cholangiocarcinoma patients to identify candidate epitopes for immunotherapy. METHODS: Twenty-six TAAs were selected, and the expression of TAAs in 6 cholangiocarcinoma cell lines and 9 specimens were measured using real-time polymerase chain reaction (PCR). CTL responses against 38 TAA-derived epitopes were measured using samples from 26 cholangiocarcinoma patients by interferon-γ enzyme linked immunospot (ELISPOT)-assay. RESULTS: Most TAAs were expressed in cholangiocarcinoma cell lines and specimens in PCR. Epitopes that stimulated a specific immune response were defined as those that elicited a CTL response in more than 3 patients and little response in healthy volunteers, as measured by ELISPOT-assay. Based on these criteria, there were 18 epitopes that stimulated specific immune responses: squamous cell carcinoma antigen recognized by T cells (SART)1(690) , P53(161) , multidrug resistance-associated protein (MRP)3(503) , Survivin2B(80) , melanoma-associated antigen (MAGE)-A4(143) , receptor tyrosine kinase ErbB-2/neu (Her2/neu)(63) , Wilms tumour (WT1)(235) , WT1(417) , β-catenin(29) , carcinoembryonic antigen (CEA)(268) , CEA(652) , epithelial cell adhesion molecule (EpCAM)(173) , enhancer of zeste homolog (EZH)2(291) , mucin 5AC (MUC5AC)(716) , glypican-3 (GPC3)(298) and kinesin family member 20A (KIF20A)(66) . Furthermore, the absolute number of lymphocytes in peripheral blood was significantly correlated with the TAA-specific response. Lastly, the overall survival was significantly prolonged in patients with 2 or more TAA-specific CTL responses compared with none to one. CONCLUSIONS: These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy.","Source":"PubMed","category":"ANIMAL","training_data":"Immune responses against tumour-associated antigen-derived cytotoxic T lymphocyte epitopes in cholangiocarcinoma patients BACKGROUND & AIMS: Immunotherapy is a promising treatment option for cholangiocarcinoma. We compared cytotoxic T lymphocyte (CTL) responses against several tumour-associated antigen (TAA)-derived epitopes in cholangiocarcinoma patients to identify candidate epitopes for immunotherapy. METHODS: Twenty-six TAAs were selected, and the expression of TAAs in 6 cholangiocarcinoma cell lines and 9 specimens were measured using real-time polymerase chain reaction (PCR). CTL responses against 38 TAA-derived epitopes were measured using samples from 26 cholangiocarcinoma patients by interferon-γ enzyme linked immunospot (ELISPOT)-assay. RESULTS: Most TAAs were expressed in cholangiocarcinoma cell lines and specimens in PCR. Epitopes that stimulated a specific immune response were defined as those that elicited a CTL response in more than 3 patients and little response in healthy volunteers, as measured by ELISPOT-assay. Based on these criteria, there were 18 epitopes that stimulated specific immune responses: squamous cell carcinoma antigen recognized by T cells (SART)1(690) , P53(161) , multidrug resistance-associated protein (MRP)3(503) , Survivin2B(80) , melanoma-associated antigen (MAGE)-A4(143) , receptor tyrosine kinase ErbB-2/neu (Her2/neu)(63) , Wilms tumour (WT1)(235) , WT1(417) , β-catenin(29) , carcinoembryonic antigen (CEA)(268) , CEA(652) , epithelial cell adhesion molecule (EpCAM)(173) , enhancer of zeste homolog (EZH)2(291) , mucin 5AC (MUC5AC)(716) , glypican-3 (GPC3)(298) and kinesin family member 20A (KIF20A)(66) . Furthermore, the absolute number of lymphocytes in peripheral blood was significantly correlated with the TAA-specific response. Lastly, the overall survival was significantly prolonged in patients with 2 or more TAA-specific CTL responses compared with none to one. CONCLUSIONS: These results demonstrated several TAAs may be promising for immunotherapy for cholangiocarcinoma, and patients with high lymphocyte counts may benefit more from immunotherapy. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"aggressive surgical management gallbladder cancer cost background aggressive operative approach gallbladder cancer advocated improved long term survival data short term outcomes lacking therefore purpose study analyze postoperative outcomes patients undergoing operative management gallbladder cancer methods data american college surgeons national surgical quality improvement program 2005 2009 queried patients diagnosis gallbladder cancer outcomes included serious morbidity overall morbidity mortality results 613 patients identified median age 67 years 64 female potentially curative operation performed 424 69 patients including cholecystectomy alone n 150 35 partial hepatectomy n 249 59 extensive hepatectomy n 25 6 overall morbidity rates procedures 21 19 28 respectively mortality greater p 001 patients undergoing extensive hepatectomy 16 compared undergoing cholecystectomy 7 partial hepatectomy 2 conclusion partial hepatectomy common procedure performed gallbladder cancer safe operation small minority younger healthier patients undergoes extensive hepatectomy mortality operation greater analysis suggests patients gallbladder cancer managed high volume centers stn","probabilities":0.9799733,"Title":"Aggressive Surgical Management Of Gallbladder Cancer: At What Cost?","Abstract":"Background: An aggressive operative approach to gallbladder cancer has been advocated because of improved long-term survival, but data on short-term outcomes are lacking. Therefore, the purpose of this study was to analyze the postoperative outcomes of patients undergoing operative management of gallbladder cancer. \r\n\r\n Methods: Data from the American College of Surgeons-National Surgical Quality Improvement Program (2005-2009) were queried for patients with a diagnosis of gallbladder cancer. Outcomes included serious morbidity, overall morbidity, and mortality. \r\n\r\n Results: For the 613 patients identified, the median age was 67 years, and 64% were female. A potentially curative operation was performed in 424 (69%) patients, including cholecystectomy alone (n =150, 35%), partial hepatectomy (n = 249, 59%), and extensive hepatectomy (n = 25, 6%). Overall morbidity rates for these procedures were 21%, 19%, and 28%, respectively. Mortality was greater (P < .001) in patients undergoing extensive hepatectomy (16%) compared with those undergoing cholecystectomy (7%) or partial hepatectomy (2%). \r\n\r\n Conclusion: Partial hepatectomy is the most common procedure performed for gallbladder cancer and is a safe operation. A small minority of younger, healthier patients undergoes an extensive hepatectomy, but the mortality of this operation is greater. This analysis suggests that patients with gallbladder cancer should be managed at high-volume centers.","Source":"STN","category":"HUMAN","training_data":"Aggressive Surgical Management Of Gallbladder Cancer: At What Cost? Background: An aggressive operative approach to gallbladder cancer has been advocated because of improved long-term survival, but data on short-term outcomes are lacking. Therefore, the purpose of this study was to analyze the postoperative outcomes of patients undergoing operative management of gallbladder cancer. \r\n\r\n Methods: Data from the American College of Surgeons-National Surgical Quality Improvement Program (2005-2009) were queried for patients with a diagnosis of gallbladder cancer. Outcomes included serious morbidity, overall morbidity, and mortality. \r\n\r\n Results: For the 613 patients identified, the median age was 67 years, and 64% were female. A potentially curative operation was performed in 424 (69%) patients, including cholecystectomy alone (n =150, 35%), partial hepatectomy (n = 249, 59%), and extensive hepatectomy (n = 25, 6%). Overall morbidity rates for these procedures were 21%, 19%, and 28%, respectively. Mortality was greater (P < .001) in patients undergoing extensive hepatectomy (16%) compared with those undergoing cholecystectomy (7%) or partial hepatectomy (2%). \r\n\r\n Conclusion: Partial hepatectomy is the most common procedure performed for gallbladder cancer and is a safe operation. A small minority of younger, healthier patients undergoes an extensive hepatectomy, but the mortality of this operation is greater. This analysis suggests that patients with gallbladder cancer should be managed at high-volume centers. STN","prediction_labels":"HUMAN"},{"cleaned":"liver cancer cell origin molecular class effects patient prognosis primary liver cancer second leading cause cancer related death worldwide therefore major public health challenge review hypotheses cell origin liver tumorigenesis clarify classes liver cancer based molecular features affect patient prognosis primary liver cancer comprises hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icca rare tumors notably fibrolamellar carcinoma hepatoblastoma molecular clinical features hcc versus icca distinct conditions overlapping risk factors pathways oncogenesis better understanding cell types originating liver cancer aid exploring molecular mechanisms carcinogenesis therapeutic options molecular studies identified adult hepatocytes cell origin cells proposed transform directly hcc cells via sequence genetic alterations dedifferentiate hepatocyte precursor cells become hcc cells express progenitor cell markers transdifferentiate biliary like cells give rise icca alternatively progenitor cells also give rise hccs iccas markers progenitor cells advances genome profiling next generation sequencing led classification hccs based molecular features assigned categories proliferation progenitor proliferation transforming growth factor wnt catenin 1 iccas assigned categories proliferation inflammation overall proliferation subclasses associated aggressive phenotype poor outcome patients although specific signatures refined prognostic abilities analyses genetic alterations identified might targeted therapeutically fusions fgfr2 gene mutations genes encoding isocitrate dehydrogenases approximately 60 iccas amplifications 11q13 6p21 approximately 15 hccs studies alterations needed used biomarkers clinical decision making pubmed","probabilities":0.962963,"Title":"Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis","Abstract":"Primary liver cancer is the second leading cause of cancer-related death worldwide and therefore a major public health challenge. We review hypotheses of the cell of origin of liver tumorigenesis and clarify the classes of liver cancer based on molecular features and how they affect patient prognosis. Primary liver cancer comprises hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC versus iCCA are distinct, but these conditions have overlapping risk factors and pathways of oncogenesis. A better understanding of the cell types originating liver cancer can aid in exploring molecular mechanisms of carcinogenesis and therapeutic options. Molecular studies have identified adult hepatocytes as the cell of origin. These cells have been proposed to transform directly into HCC cells (via a sequence of genetic alterations), to dedifferentiate into hepatocyte precursor cells (which then become HCC cells that express progenitor cell markers), or to transdifferentiate into biliary-like cells (which give rise to iCCA). Alternatively, progenitor cells also give rise to HCCs and iCCAs with markers of progenitor cells. Advances in genome profiling and next-generation sequencing have led to the classification of HCCs based on molecular features and assigned them to categories such as proliferation-progenitor, proliferation-transforming growth factor β, and Wnt-catenin β1. iCCAs have been assigned to categories of proliferation and inflammation. Overall, proliferation subclasses are associated with a more aggressive phenotype and poor outcome of patients, although more specific signatures have refined our prognostic abilities. Analyses of genetic alterations have identified those that might be targeted therapeutically, such as fusions in the FGFR2 gene and mutations in genes encoding isocitrate dehydrogenases (in approximately 60% of iCCAs) or amplifications at 11q13 and 6p21 (in approximately 15% of HCCs). Further studies of these alterations are needed before they can be used as biomarkers in clinical decision making.","Source":"PubMed","category":"HUMAN","training_data":"Liver Cancer Cell of Origin, Molecular Class, and Effects on Patient Prognosis Primary liver cancer is the second leading cause of cancer-related death worldwide and therefore a major public health challenge. We review hypotheses of the cell of origin of liver tumorigenesis and clarify the classes of liver cancer based on molecular features and how they affect patient prognosis. Primary liver cancer comprises hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (iCCA), and other rare tumors, notably fibrolamellar carcinoma and hepatoblastoma. The molecular and clinical features of HCC versus iCCA are distinct, but these conditions have overlapping risk factors and pathways of oncogenesis. A better understanding of the cell types originating liver cancer can aid in exploring molecular mechanisms of carcinogenesis and therapeutic options. Molecular studies have identified adult hepatocytes as the cell of origin. These cells have been proposed to transform directly into HCC cells (via a sequence of genetic alterations), to dedifferentiate into hepatocyte precursor cells (which then become HCC cells that express progenitor cell markers), or to transdifferentiate into biliary-like cells (which give rise to iCCA). Alternatively, progenitor cells also give rise to HCCs and iCCAs with markers of progenitor cells. Advances in genome profiling and next-generation sequencing have led to the classification of HCCs based on molecular features and assigned them to categories such as proliferation-progenitor, proliferation-transforming growth factor β, and Wnt-catenin β1. iCCAs have been assigned to categories of proliferation and inflammation. Overall, proliferation subclasses are associated with a more aggressive phenotype and poor outcome of patients, although more specific signatures have refined our prognostic abilities. Analyses of genetic alterations have identified those that might be targeted therapeutically, such as fusions in the FGFR2 gene and mutations in genes encoding isocitrate dehydrogenases (in approximately 60% of iCCAs) or amplifications at 11q13 and 6p21 (in approximately 15% of HCCs). Further studies of these alterations are needed before they can be used as biomarkers in clinical decision making. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative neutrophil lymphocyte ratio predicts tumor infiltrating cd8 cells biliary tract cancer background aim study evaluated prognostic significance preoperative neutrophil lymphocyte ratio nlr cd8 tumor infiltrating lymphocytes tils whether preoperative nlr associated cd8 tils biliary tract cancers btcs patients methods total 154 patients btcs underwent surgery enrolled study obtained neutrophil lymphocyte counts calculated nlr preoperative peripheral blood samples cd8 tils identified immunohistochemical staining results overall survival os recurrence free survival rfs patients high nlr shorter low nlr os rfs patients high cd8 tils longer low cd8 tils preoperative nlr cd8 tils negatively correlated conclusion nlr cd8 tils associated os rfs btcs nlr predict cd8 tils infiltrating cancer microenvironment stn","probabilities":0.9799733,"Title":"Preoperative Neutrophil-To-Lymphocyte Ratio Predicts Tumor-Infiltrating Cd8(+) T Cells In Biliary Tract Cancer","Abstract":"Background/aim: This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8+ tumor-infiltrating lymphocytes (TILs), and whether preoperative NLR was associated with CD8+ TILs in biliary tract cancers (BTCs). \r\n\r\n Patients and methods: A total of 154 patients with BTCs who underwent surgery were enrolled in this study. We obtained neutrophil and lymphocyte counts, and calculated NLR from preoperative peripheral blood samples. CD8+ TILs were identified by immunohistochemical staining. \r\n\r\n Results: The overall survival (OS) and recurrence-free survival (RFS) of patients with high NLR were shorter than those with low NLR. The OS and RFS of patients with high CD8+ TILs were longer than those with low CD8+ TILs. Preoperative NLR and CD8+ TILs were negatively correlated. \r\n\r\n Conclusion: NLR and CD8+ TILs were associated with OS and RFS in BTCs. NLR can predict CD8+ TILs infiltrating the cancer microenvironment.","Source":"STN","category":"HUMAN","training_data":"Preoperative Neutrophil-To-Lymphocyte Ratio Predicts Tumor-Infiltrating Cd8(+) T Cells In Biliary Tract Cancer Background/aim: This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8+ tumor-infiltrating lymphocytes (TILs), and whether preoperative NLR was associated with CD8+ TILs in biliary tract cancers (BTCs). \r\n\r\n Patients and methods: A total of 154 patients with BTCs who underwent surgery were enrolled in this study. We obtained neutrophil and lymphocyte counts, and calculated NLR from preoperative peripheral blood samples. CD8+ TILs were identified by immunohistochemical staining. \r\n\r\n Results: The overall survival (OS) and recurrence-free survival (RFS) of patients with high NLR were shorter than those with low NLR. The OS and RFS of patients with high CD8+ TILs were longer than those with low CD8+ TILs. Preoperative NLR and CD8+ TILs were negatively correlated. \r\n\r\n Conclusion: NLR and CD8+ TILs were associated with OS and RFS in BTCs. NLR can predict CD8+ TILs infiltrating the cancer microenvironment. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors surgical resection intrahepatic hilar distal cholangiocarcinoma background prognosis patients cholangiocarcinoma unsatisfactory therefore evaluation prognostic factors establishment new therapeutic strategies needed improve long term survival aim study identify useful prognostic factors patients intrahepatic hilar distal cholangiocarcinoma materials methods records 127 patients cholangiocarcinoma 21 intrahepatic cholangiocarcinoma 50 hilar cholangiocarcinoma 56 distal cholangiocarcinoma underwent surgical resection reviewed retrospectively relationships survival clinicopathological factors including patient demographics tumor characteristics evaluated using univariate multivariate analysis results 127 patients overall 1 3 5 year survival rates 80 51 40 respectively univariate analysis revealed adjuvant chemotherapy p 049 tumor differentiation p 014 lymph node metastasis p 001 surgical margin status p 001 uicc pt factor p 001 uicc stage p 001 associated significantly survival uicc pt factor p 007 adjuvant chemotherapy p 009 surgical margin status p 012 lymph node metastasis p 014 remained independently associated long term survival multivariate analysis 5 year survival rates patients without positive surgical margins 13 49 respectively 5 year survival rates patients treated without adjuvant chemotherapy 47 36 respectively conclusions r0 resection adjuvant chemotherapy may mandatory achieve long term survival patients cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Prognostic Factors After Surgical Resection For Intrahepatic Hilar And Distal Cholangiocarcinoma","Abstract":"Background: The prognosis of patients with cholangiocarcinoma is unsatisfactory. Therefore, evaluation of prognostic factors and establishment of new therapeutic strategies are needed to improve their long-term survival. The aim of this study was to identify useful prognostic factors for patients with intrahepatic, hilar, and distal cholangiocarcinoma. \r\n\r\n Materials and methods: Records of 127 patients with cholangiocarcinoma (21 with intrahepatic cholangiocarcinoma, 50 with hilar cholangiocarcinoma, and 56 with distal cholangiocarcinoma) who underwent surgical resection were reviewed retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis. \r\n\r\n Results: For all 127 patients, overall 1-, 3-, 5-year survival rates were 80, 51, and 40%, respectively. Univariate analysis revealed that adjuvant chemotherapy (P = .049), tumor differentiation (P = .014), lymph node metastasis (P < .001), surgical margin status (P < .001), UICC pT factor (P < .001), and UICC stage (P < .001) were associated significantly with survival. UICC pT factor (P = .007), adjuvant chemotherapy (P = .009), surgical margin status (P = .012), and lymph node metastasis (P = .014) remained independently associated with long-term survival by multivariate analysis. The 5-year survival rates of patients with or without positive surgical margins were 13 and 49%, respectively. The 5-year survival rates of patients treated with or without adjuvant chemotherapy were 47 and 36%, respectively. \r\n\r\n Conclusions: R0 resection and adjuvant chemotherapy may be mandatory to achieve long-term survival for patients with cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Prognostic Factors After Surgical Resection For Intrahepatic Hilar And Distal Cholangiocarcinoma Background: The prognosis of patients with cholangiocarcinoma is unsatisfactory. Therefore, evaluation of prognostic factors and establishment of new therapeutic strategies are needed to improve their long-term survival. The aim of this study was to identify useful prognostic factors for patients with intrahepatic, hilar, and distal cholangiocarcinoma. \r\n\r\n Materials and methods: Records of 127 patients with cholangiocarcinoma (21 with intrahepatic cholangiocarcinoma, 50 with hilar cholangiocarcinoma, and 56 with distal cholangiocarcinoma) who underwent surgical resection were reviewed retrospectively. Relationships between survival and clinicopathological factors including patient demographics and tumor characteristics were evaluated using univariate and multivariate analysis. \r\n\r\n Results: For all 127 patients, overall 1-, 3-, 5-year survival rates were 80, 51, and 40%, respectively. Univariate analysis revealed that adjuvant chemotherapy (P = .049), tumor differentiation (P = .014), lymph node metastasis (P < .001), surgical margin status (P < .001), UICC pT factor (P < .001), and UICC stage (P < .001) were associated significantly with survival. UICC pT factor (P = .007), adjuvant chemotherapy (P = .009), surgical margin status (P = .012), and lymph node metastasis (P = .014) remained independently associated with long-term survival by multivariate analysis. The 5-year survival rates of patients with or without positive surgical margins were 13 and 49%, respectively. The 5-year survival rates of patients treated with or without adjuvant chemotherapy were 47 and 36%, respectively. \r\n\r\n Conclusions: R0 resection and adjuvant chemotherapy may be mandatory to achieve long-term survival for patients with cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"evaluation fully covered self expanding metal stent flared ends malignant biliary obstruction multicenter study background aims limited data available regarding fully covered metal stents management malignant distal biliary strictures aim study evaluate safety fully covered self expanding metal stent fcsems flared ends treating malignant biliary strictures report long term retrospective analysis 6 centers methods total 260 patients 142 males median age 68 y underwent endoscopic retrograde cholangiopancreatography placement fcsems wallflex boston scientific natick ma palliation obstructive jaundice setting pancreatic adenocarcinoma 169 metastatic disease 36 cholangiocarcinoma 23 ampullary cancer 19 13 patients evaluated clinically follow biochemical tests liver function obtained data recorded following variables patient survival duration stent patency need subsequent biliary intervention complications results total 266 fcsems placed 260 patients median survival 100 days range 7 531 d mean follow 134 118 days range 4 519 d biliary decompression successful 252 patients 97 end study period 121 alive patent stent 65 patients died patent stent 40 patients successfully bridged surgery 8 patients patent stent removed need stenting 18 patients lost follow five patients successfully placed fcsems considered failure due following reason migration 2 cholangitis 1 stent occlusion 1 removal management proximal biliary obstruction 1 two additional patients experienced migration require fcsems removal replacement stent replacement required 10 patients 6 second fcsems placed remaining 4 failure group underwent replacement either uncovered stents plastic stents complications managed conservatively included pain 2 postendoscopic retrograde cholangiopancreatography pancreatitis 4 fever 1 retroperitoneal perforation 1 postsphincterotomy bleeding 1 mean patency duration 328 days se 19 04 patency percentage 83 3 months 63 6 months 48 5 12 months conclusions management malignant distal biliary strictures fully covered wallflex stent acceptable patency complication rates long term prospective data required confirm observation pubmed","probabilities":0.9799733,"Title":"Evaluation of a fully covered self-expanding metal stent with flared ends in malignant biliary obstruction: a multicenter study","Abstract":"BACKGROUND AND AIMS: Limited data are available regarding fully covered metal stents in the management of malignant distal biliary strictures. The aim of this study was to evaluate the safety of a fully covered self-expanding metal stent (FCSEMS) with flared ends, in treating malignant biliary strictures. We report our long-term retrospective analysis from 6 centers. METHODS: A total of 260 patients (142 males, median age 68 y) underwent endoscopic retrograde cholangiopancreatography with placement of FCSEMS (WallFlex; Boston Scientific, Natick, MA) for the palliation of obstructive jaundice in the setting of pancreatic adenocarcinoma (169), metastatic disease (36), cholangiocarcinoma (23), ampullary cancer (19), or other (13). Patients were evaluated clinically in follow-up and biochemical tests of liver function were obtained. Data were recorded for the following variables: patient survival, duration of stent patency, the need for subsequent biliary intervention, and complications. RESULTS: A total of 266 FCSEMS were placed in 260 patients. There was a median survival of 100 days (range, 7 to 531 d). There was a mean follow-up of 134±118 days (range, 4 to 519 d). Biliary decompression was successful in 252 patients (97%). At the end of the study period, 121 were alive with a patent stent, 65 patients died with a patent stent, 40 patients were successfully bridged to surgery, 8 patients had their patent stent removed and had no need for further stenting, and 18 patients were lost to follow-up. Five patients who had a successfully placed FCSEMS were considered a failure due to the following reason: migration (2), cholangitis (1), stent occlusion (1), and removal for management of proximal biliary obstruction (1). Two additional patients experienced migration that did not require FCSEMS removal or replacement. Stent replacement was required in 10 patients, of whom 6 had a second FCSEMS placed. The remaining 4 were in the failure group and underwent replacement with either uncovered stents or plastic stents. Other complications, managed conservatively, included pain (2), postendoscopic retrograde cholangiopancreatography pancreatitis (4), fever (1), retroperitoneal perforation (1), and postsphincterotomy bleeding (1). The mean patency duration was 328 days (SE 19.04). The patency percentage was 83% at 3 months, 63% at 6 months, and 48.5% at 12 months. CONCLUSIONS: In the management of malignant distal biliary strictures, the fully covered WallFlex stent has acceptable patency and complication rates. Further long-term prospective data are required to confirm this observation.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of a fully covered self-expanding metal stent with flared ends in malignant biliary obstruction: a multicenter study BACKGROUND AND AIMS: Limited data are available regarding fully covered metal stents in the management of malignant distal biliary strictures. The aim of this study was to evaluate the safety of a fully covered self-expanding metal stent (FCSEMS) with flared ends, in treating malignant biliary strictures. We report our long-term retrospective analysis from 6 centers. METHODS: A total of 260 patients (142 males, median age 68 y) underwent endoscopic retrograde cholangiopancreatography with placement of FCSEMS (WallFlex; Boston Scientific, Natick, MA) for the palliation of obstructive jaundice in the setting of pancreatic adenocarcinoma (169), metastatic disease (36), cholangiocarcinoma (23), ampullary cancer (19), or other (13). Patients were evaluated clinically in follow-up and biochemical tests of liver function were obtained. Data were recorded for the following variables: patient survival, duration of stent patency, the need for subsequent biliary intervention, and complications. RESULTS: A total of 266 FCSEMS were placed in 260 patients. There was a median survival of 100 days (range, 7 to 531 d). There was a mean follow-up of 134±118 days (range, 4 to 519 d). Biliary decompression was successful in 252 patients (97%). At the end of the study period, 121 were alive with a patent stent, 65 patients died with a patent stent, 40 patients were successfully bridged to surgery, 8 patients had their patent stent removed and had no need for further stenting, and 18 patients were lost to follow-up. Five patients who had a successfully placed FCSEMS were considered a failure due to the following reason: migration (2), cholangitis (1), stent occlusion (1), and removal for management of proximal biliary obstruction (1). Two additional patients experienced migration that did not require FCSEMS removal or replacement. Stent replacement was required in 10 patients, of whom 6 had a second FCSEMS placed. The remaining 4 were in the failure group and underwent replacement with either uncovered stents or plastic stents. Other complications, managed conservatively, included pain (2), postendoscopic retrograde cholangiopancreatography pancreatitis (4), fever (1), retroperitoneal perforation (1), and postsphincterotomy bleeding (1). The mean patency duration was 328 days (SE 19.04). The patency percentage was 83% at 3 months, 63% at 6 months, and 48.5% at 12 months. CONCLUSIONS: In the management of malignant distal biliary strictures, the fully covered WallFlex stent has acceptable patency and complication rates. Further long-term prospective data are required to confirm this observation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"circulating cd14 cd16 monocyte levels predict tissue invasive character cholangiocarcinoma chronic inflammation risk factor cancer development driven part monocyte macrophages many cancers exhibit pro tumorigenic activity study identified elevation cd14 cd16 minor blood monocyte subpopulation cholangiocarcinoma cca patients compared normal biliary disease patient specimens tumour association suggested observation elevated level decreased normal tumour resection moreover elevated level cd14 cd16 monocytes cca patient blood correlated degree mac387 positive recent blood derived macrophage migrant specific marker tumour associated macrophage infiltration determined immunohistochemistry cd14 cd16 monocytes suggested enhance tumour progression subpopulation possesses high expression adhesion molecules cd11c cd49d cd54 scavenger receptor cd163 enable adhere strongly endothelial cells ii peripheral blood monocytes cca patients express high levels growth angiogenic factor related genes epiregulin vegf cxcl3 elevation peripheral cd14 cd16 monocyte levels associated features associated poor prognosis cca parameters non papillary type high number tissue macrophages data indicate cd14 cd16 monocytes cca patients pro tumorigenic characteristics may associate rapid tumour progression poor patient outcome confirmed subsequent studies level cd14 cd16 monocytes may serve marker disease activity cca patients serve target pathogenic macrophage specific drug development stn","probabilities":0.7966102,"Title":"Circulating Cd14(+) Cd16(+) Monocyte Levels Predict Tissue Invasive Character Of Cholangiocarcinoma","Abstract":"Chronic inflammation as a risk factor for cancer development is driven in part by monocyte/macrophages, which in many cancers exhibit pro-tumorigenic activity. In this study we identified elevation in CD14(+) CD16(+) , a minor blood monocyte subpopulation in cholangiocarcinoma (CCA) patients, compared to normal and biliary disease patient specimens. Tumour association was suggested by the observation that this elevated level decreased to normal after tumour resection. Moreover, the elevated level of CD14(+) CD16(+) monocytes in CCA patient blood correlated with degree of MAC387-positive (recent blood-derived macrophage migrant-specific marker) tumour-associated macrophage infiltration as determined by immunohistochemistry. These CD14(+) CD16(+) monocytes were suggested to enhance tumour progression as this subpopulation possesses (i) high expression of adhesion molecules (CD11c, CD49d, and CD54) and scavenger receptor (CD163), which enable them to adhere strongly to endothelial cells, and (ii) that peripheral blood monocytes from CCA patients express high levels of growth and angiogenic factor-related genes (epiregulin, VEGF-A and CXCL3). Elevation of peripheral CD14(+) CD16(+) monocyte levels was associated with features associated with poor prognosis CCA parameters (non-papillary type and high number of tissue macrophages). These data indicate that the CD14(+) CD16(+) monocytes from CCA patients with pro-tumorigenic characteristics may associate with rapid tumour progression and poor patient outcome. If confirmed in subsequent studies, the level of CD14(+) CD16(+) monocytes may serve as a marker for disease activity in CCA patients and serve as a target for pathogenic macrophage specific drug development.","Source":"STN","category":"HUMAN","training_data":"Circulating Cd14(+) Cd16(+) Monocyte Levels Predict Tissue Invasive Character Of Cholangiocarcinoma Chronic inflammation as a risk factor for cancer development is driven in part by monocyte/macrophages, which in many cancers exhibit pro-tumorigenic activity. In this study we identified elevation in CD14(+) CD16(+) , a minor blood monocyte subpopulation in cholangiocarcinoma (CCA) patients, compared to normal and biliary disease patient specimens. Tumour association was suggested by the observation that this elevated level decreased to normal after tumour resection. Moreover, the elevated level of CD14(+) CD16(+) monocytes in CCA patient blood correlated with degree of MAC387-positive (recent blood-derived macrophage migrant-specific marker) tumour-associated macrophage infiltration as determined by immunohistochemistry. These CD14(+) CD16(+) monocytes were suggested to enhance tumour progression as this subpopulation possesses (i) high expression of adhesion molecules (CD11c, CD49d, and CD54) and scavenger receptor (CD163), which enable them to adhere strongly to endothelial cells, and (ii) that peripheral blood monocytes from CCA patients express high levels of growth and angiogenic factor-related genes (epiregulin, VEGF-A and CXCL3). Elevation of peripheral CD14(+) CD16(+) monocyte levels was associated with features associated with poor prognosis CCA parameters (non-papillary type and high number of tissue macrophages). These data indicate that the CD14(+) CD16(+) monocytes from CCA patients with pro-tumorigenic characteristics may associate with rapid tumour progression and poor patient outcome. If confirmed in subsequent studies, the level of CD14(+) CD16(+) monocytes may serve as a marker for disease activity in CCA patients and serve as a target for pathogenic macrophage specific drug development. STN","prediction_labels":"HUMAN"},{"cleaned":"coffee consumption risk gallbladder cancer prospective study evidence indicates coffee consumption may reduce risk gallstone disease strongly associated increased risk gallbladder cancer association coffee consumption gallbladder cancer incidence examined prospective cohort study 72 680 swedish adults aged 45 83 years free cancer reported coffee consumption baseline gallbladder cancers ascertained linkage swedish cancer register data analyzed using cox proportional hazards regression models statistical tests two sided 967 377 person years follow 74 gallbladder cancer case patients identified compared consumption one less cups coffee per day multivariable hazard ratios 0 76 95 confidence interval ci 0 41 1 41 two cups per day 0 50 95 ci 0 24 1 06 three cups per day 0 41 95 ci 0 20 0 83 four cups per day conclusion coffee consumption associated reduced risk gallbladder cancer pubmed","probabilities":0.9799733,"Title":"Coffee Consumption and Risk of Gallbladder Cancer in a Prospective Study","Abstract":"Evidence indicates that coffee consumption may reduce the risk of gallstone disease, which is strongly associated with increased risk of gallbladder cancer. The association between coffee consumption and gallbladder cancer incidence was examined in a prospective cohort study of 72 680 Swedish adults (aged 45 - 83 years) who were free of cancer and reported their coffee consumption at baseline. Gallbladder cancers were ascertained by linkage with the Swedish Cancer Register. The data were analyzed using Cox proportional hazards regression models. Statistical tests were two-sided. During 967 377 person-years of follow-up, 74 gallbladder cancer case patients were identified. Compared with consumption of one or less cups of coffee per day, the multivariable hazard ratios were 0.76 (95% confidence interval [CI] = 0.41 to 1.41) for two cups per day, 0.50 (95% CI = 0.24 to 1.06) for three cups per day, and 0.41 (95% CI = 0.20 to 0.83) for four or more cups per day. In conclusion, coffee consumption is associated with a reduced risk of gallbladder cancer.","Source":"PubMed","category":"HUMAN","training_data":"Coffee Consumption and Risk of Gallbladder Cancer in a Prospective Study Evidence indicates that coffee consumption may reduce the risk of gallstone disease, which is strongly associated with increased risk of gallbladder cancer. The association between coffee consumption and gallbladder cancer incidence was examined in a prospective cohort study of 72 680 Swedish adults (aged 45 - 83 years) who were free of cancer and reported their coffee consumption at baseline. Gallbladder cancers were ascertained by linkage with the Swedish Cancer Register. The data were analyzed using Cox proportional hazards regression models. Statistical tests were two-sided. During 967 377 person-years of follow-up, 74 gallbladder cancer case patients were identified. Compared with consumption of one or less cups of coffee per day, the multivariable hazard ratios were 0.76 (95% confidence interval [CI] = 0.41 to 1.41) for two cups per day, 0.50 (95% CI = 0.24 to 1.06) for three cups per day, and 0.41 (95% CI = 0.20 to 0.83) for four or more cups per day. In conclusion, coffee consumption is associated with a reduced risk of gallbladder cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"identification potential prognostic long non coding rna predicting survival intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc aggressive biliary epithelial tumor poor prognosis increasing evidences long non coding rnas lncrnas dysregulated multifarious tumors revealing potential significant role lncrnas tumorigenesis used icc dataset retrieved cancer genome atlas gene expression omnibus database obtain lncrnas expression profiles identify potential prognostic lncrnas predicting prognosis icc univariate multivariate cox regression analyses performed construct prognostic index pi furthermore coexpression analysis functional assessment performed initially investigate function prognostic lncrnas total 255 differentially expressed lncrnas delncrnas identified among two rna sequencing dataset total 63 icc patients 98 samples using r platform thirteen 255 delncrnas identified prognostic lncrnas used pi patients high pi associated poor prognostic p 0064 cox regression showed consistent result p 042 time dependent receiver operating characteristic analysis showed pi performed well icc survival prediction area curve 0 921 0 801 0 717 1 3 5 year survival respectively conclusion included 13 identified prognostic delncrnas constructed prognostic signature pi icc patient higher pi associated poorer prognosis however clinical role well biological functions constructed pi prognostic delncrnas need verified future study pubmed","probabilities":0.9799733,"Title":"Identification of potential prognostic long non-coding RNA for predicting survival in intrahepatic cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary epithelial tumor with poor prognosis. There are increasing evidences that long non-coding RNAs (lncRNAs) are dysregulated in multifarious tumors, revealing potential significant role of lncRNAs in tumorigenesis.We used the ICC dataset retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus database to obtain the lncRNAs expression profiles and identify potential prognostic lncRNAs for predicting the prognosis in ICC. Univariate and multivariate Cox regression analyses were performed to construct a prognostic index (PI). Furthermore, coexpression analysis and functional assessment were performed to initially investigate the function of these prognostic lncRNAs.A total of 255 differentially expressed lncRNAs (DElncRNAs) were identified among two RNA sequencing dataset of a total 63 ICC patients with 98 samples using R platform. Thirteen of 255 DElncRNAs were identified as prognostic lncRNAs and used for a PI. Patients with high PI were associated with poor prognostic (P = .0064), and the Cox regression showed consistent result (P = .042). The time-dependent receiver operating characteristic analysis showed the PI performed well in ICC survival prediction with an area under curve of 0.921, 0.801, and 0.717 for 1-, 3-, and 5-year survival, respectively.In conclusion, we included 13 identified prognostic DElncRNAs and constructed a prognostic signature/PI. ICC patient with higher PI was associated with poorer prognosis. However, the clinical role as well as biological functions of constructed PI and these prognostic DElncRNAs need to be verified in future study.","Source":"PubMed","category":"HUMAN","training_data":"Identification of potential prognostic long non-coding RNA for predicting survival in intrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is an aggressive biliary epithelial tumor with poor prognosis. There are increasing evidences that long non-coding RNAs (lncRNAs) are dysregulated in multifarious tumors, revealing potential significant role of lncRNAs in tumorigenesis.We used the ICC dataset retrieved from The Cancer Genome Atlas and the Gene Expression Omnibus database to obtain the lncRNAs expression profiles and identify potential prognostic lncRNAs for predicting the prognosis in ICC. Univariate and multivariate Cox regression analyses were performed to construct a prognostic index (PI). Furthermore, coexpression analysis and functional assessment were performed to initially investigate the function of these prognostic lncRNAs.A total of 255 differentially expressed lncRNAs (DElncRNAs) were identified among two RNA sequencing dataset of a total 63 ICC patients with 98 samples using R platform. Thirteen of 255 DElncRNAs were identified as prognostic lncRNAs and used for a PI. Patients with high PI were associated with poor prognostic (P = .0064), and the Cox regression showed consistent result (P = .042). The time-dependent receiver operating characteristic analysis showed the PI performed well in ICC survival prediction with an area under curve of 0.921, 0.801, and 0.717 for 1-, 3-, and 5-year survival, respectively.In conclusion, we included 13 identified prognostic DElncRNAs and constructed a prognostic signature/PI. ICC patient with higher PI was associated with poorer prognosis. However, the clinical role as well as biological functions of constructed PI and these prognostic DElncRNAs need to be verified in future study. PubMed","prediction_labels":"HUMAN"},{"cleaned":"potential therapeutic value primary tumor resection ampullary cancer patients distant metastases initial diagnosis population based study objective evaluate therapeutic value primary tumor resection ptr metastatic ampullary cancer initial presentation patients methods patients metastatic ampullary cancer identified surveillance epidemiology end results database propensity score matching psm performed balance characteristics cohort kaplan meier analyses log rank tests multivariate cox regression models employed evaluate therapeutic value ptr results total 346 patients metastatic ampullary cancer identified 2004 2014 90 patients screened psm ptr associated favorable overall survival os cancer specific survival css psm ptr vs ptr 16 0 95 ci 9 0 22 0 vs 8 0 95 ci 5 0 11 0 median os 22 0 95 ci 13 0 33 0 vs 9 0 95 ci 5 0 11 0 median css log rank p 0 001 patients receiving ptr plus chemotherapy showed better survival compared receiving chemotherapy median os 18 95 ci 13 27 vs 9 0 95 ci 8 0 11 0 median css 23 0 95 ci 14 0 36 0 vs 9 0 95 ci 8 0 13 0 log rank p 0 001 conclusion ptr might bring survival benefit ampullary cancer patients distant metastasis initial presentation might provide favorable prognosis combined chemotherapy stn","probabilities":0.9799733,"Title":"Potential Therapeutic Value Of Primary Tumor Resection In Ampullary Cancer Patients With Distant Metastases At Initial Diagnosis: A Population-Based Study","Abstract":"Objective: To evaluate the therapeutic value of primary tumor resection (PTR) in metastatic ampullary cancer at the initial presentation. \r\n\r\n Patients and methods: Patients with metastatic ampullary cancer were identified from Surveillance, Epidemiology and End Results database. Propensity score matching (PSM) was performed to balance the characteristics of our cohort. Kaplan-Meier analyses, log-rank tests and multivariate Cox regression models were employed to evaluate the therapeutic value of PTR. \r\n\r\n Results: A total of 346 patients with metastatic ampullary cancer were identified from 2004 to 2014 and 90 patients were screened by PSM. PTR was associated with favorable overall survival (OS) and cancer-specific survival (CSS) after PSM (PTR vs no-PTR: 16.0, 95% CI: 9.0-22.0 vs 8.0, 95% CI: 5.0-11.0 for median OS; 22.0, 95% CI: 13.0-33.0 vs 9.0, 95% CI: 5.0-11.0 for median CSS; both log-rank P<0.001). Patients receiving PTR plus chemotherapy showed better survival compared with those receiving only chemotherapy (median OS: 18, 95% CI: 13-27 vs 9.0, 95% CI: 8.0-11.0; median CSS: 23.0, 95% CI: 14.0-36.0 vs 9.0, 95% CI: 8.0-13.0; both log-rank P<0.001). \r\n\r\n Conclusion: PTR might bring a survival benefit to ampullary cancer patients with distant metastasis at the initial presentation and might provide a more favorable prognosis when combined with chemotherapy.","Source":"STN","category":"HUMAN","training_data":"Potential Therapeutic Value Of Primary Tumor Resection In Ampullary Cancer Patients With Distant Metastases At Initial Diagnosis: A Population-Based Study Objective: To evaluate the therapeutic value of primary tumor resection (PTR) in metastatic ampullary cancer at the initial presentation. \r\n\r\n Patients and methods: Patients with metastatic ampullary cancer were identified from Surveillance, Epidemiology and End Results database. Propensity score matching (PSM) was performed to balance the characteristics of our cohort. Kaplan-Meier analyses, log-rank tests and multivariate Cox regression models were employed to evaluate the therapeutic value of PTR. \r\n\r\n Results: A total of 346 patients with metastatic ampullary cancer were identified from 2004 to 2014 and 90 patients were screened by PSM. PTR was associated with favorable overall survival (OS) and cancer-specific survival (CSS) after PSM (PTR vs no-PTR: 16.0, 95% CI: 9.0-22.0 vs 8.0, 95% CI: 5.0-11.0 for median OS; 22.0, 95% CI: 13.0-33.0 vs 9.0, 95% CI: 5.0-11.0 for median CSS; both log-rank P<0.001). Patients receiving PTR plus chemotherapy showed better survival compared with those receiving only chemotherapy (median OS: 18, 95% CI: 13-27 vs 9.0, 95% CI: 8.0-11.0; median CSS: 23.0, 95% CI: 14.0-36.0 vs 9.0, 95% CI: 8.0-13.0; both log-rank P<0.001). \r\n\r\n Conclusion: PTR might bring a survival benefit to ampullary cancer patients with distant metastasis at the initial presentation and might provide a more favorable prognosis when combined with chemotherapy. STN","prediction_labels":"HUMAN"},{"cleaned":"extrahepatic adjacent organ involvement gallbladder carcinoma aggressive approach improves resectability outcome background involvement extrahepatic adjacent organs gall bladder cancer gbc often considered locoregionally advanced disease consider sign inoperability others perform extended radical surgery adjacent viscera resection including pancreatoduodenectomy achieve ro resection methods prospectively collected database gbc patients operated may 2006 september 2012 centre retrospectively analyzed patients extrahepatic adjacent organ involvement requiring synchronous resection involved viscera analyzed determine impact curative resection rate extent surgery results 569 patients taken surgery 327 underwent curative resection one hundred thirteen patients required resection one n 49 n 64 adjacent organs patients gastroduodenal involvement without pancreatic involvement n 63 underwent duodenal sleeve resection small area contact n 27 distal gastrectomy proximal duodenectomy wide area contact n 36 wedge resection pancreas performed seven patients minimal pancreatic involvement hepatopancreatoduodenectomy six patients extensive pancreatic involvement large retropancreatic nodes cbd excision performed 75 patients associated jaundice bile duct involvement n 54 choledochal cyst n 12 facilitate lymph node clearance n 9 colonic involvement n 33 required sleeve segmental resection colon 25 patients right hemicolectomy 8 patients resection single adjacent organ improved overall resectability 37 60 214 569 46 22 263 569 addition one adjacent organ resection improved 57 47 327 569 conclusions aggressive approach aimed resection involved adjacent viscera improves curative resection rate gbc survival r0 resection achieved limited resection cases without need pancreatoduodenectomy google scholar","probabilities":0.9799733,"Title":"Extrahepatic Adjacent Organ Involvement In Gallbladder Carcinoma: An Aggressive Approach Improves Resectability And Outcome !","Abstract":"Background: Involvement of extrahepatic adjacent organs in gall bladder cancer (GBC) is often considered as locoregionally advanced disease. While some consider it as a sign of inoperability, others perform an extended radical surgery (adjacent viscera resection including pancreatoduodenectomy) to achieve Ro resection. Methods: The prospectively collected database of GBC patients operated from May 2006 to September 2012 at our Centre was retrospectively analyzed. Patients with extrahepatic adjacent organ involvement requiring synchronous resection of involved viscera were analyzed to determine its impact on curative resection rate and extent of surgery. Results: Of the 569 patients taken up for surgery 327 underwent curative resection. One hundred and thirteen patients required resection of one (n = 49) or more (n = 64) adjacent organs. Patients with gastroduodenal involvement without pancreatic involvement (n = 63) underwent duodenal sleeve resection for small area of contact (n = 27) or distal gastrectomy with proximal duodenectomy for wide area of contact (n = 36). Wedge resection of pancreas was performed in seven patients with minimal pancreatic involvement and hepatopancreatoduodenectomy in six patients for extensive pancreatic involvement or large retropancreatic nodes. CBD excision was performed in 75 patients for associated jaundice/bile duct involvement (n = 54), choledochal cyst (n = 12) or to facilitate lymph node clearance (n = 9). Colonic involvement (n = 33) required sleeve/segmental resection of colon in 25 patients and right hemicolectomy in 8 patients. Resection of single adjacent organ improved overall resectability from 37.60% (214/569) to 46.22% (263/569) and addition of more than one adjacent organ resection improved it to 57.47% (327/569). Conclusions: Aggressive approach aimed at resection of involved adjacent viscera improves curative resection rate in GBC and survival. An R0 resection could be achieved with limited resection in most cases without a need for pancreatoduodenectomy.","Source":"Google Scholar","category":"HUMAN","training_data":"Extrahepatic Adjacent Organ Involvement In Gallbladder Carcinoma: An Aggressive Approach Improves Resectability And Outcome ! Background: Involvement of extrahepatic adjacent organs in gall bladder cancer (GBC) is often considered as locoregionally advanced disease. While some consider it as a sign of inoperability, others perform an extended radical surgery (adjacent viscera resection including pancreatoduodenectomy) to achieve Ro resection. Methods: The prospectively collected database of GBC patients operated from May 2006 to September 2012 at our Centre was retrospectively analyzed. Patients with extrahepatic adjacent organ involvement requiring synchronous resection of involved viscera were analyzed to determine its impact on curative resection rate and extent of surgery. Results: Of the 569 patients taken up for surgery 327 underwent curative resection. One hundred and thirteen patients required resection of one (n = 49) or more (n = 64) adjacent organs. Patients with gastroduodenal involvement without pancreatic involvement (n = 63) underwent duodenal sleeve resection for small area of contact (n = 27) or distal gastrectomy with proximal duodenectomy for wide area of contact (n = 36). Wedge resection of pancreas was performed in seven patients with minimal pancreatic involvement and hepatopancreatoduodenectomy in six patients for extensive pancreatic involvement or large retropancreatic nodes. CBD excision was performed in 75 patients for associated jaundice/bile duct involvement (n = 54), choledochal cyst (n = 12) or to facilitate lymph node clearance (n = 9). Colonic involvement (n = 33) required sleeve/segmental resection of colon in 25 patients and right hemicolectomy in 8 patients. Resection of single adjacent organ improved overall resectability from 37.60% (214/569) to 46.22% (263/569) and addition of more than one adjacent organ resection improved it to 57.47% (327/569). Conclusions: Aggressive approach aimed at resection of involved adjacent viscera improves curative resection rate in GBC and survival. An R0 resection could be achieved with limited resection in most cases without a need for pancreatoduodenectomy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"healthy dietary patterns incidence biliary tract gallbladder cancer prospective study women men background whether diet influences risk biliary tract cancer btc unknown examined associations two healthy dietary patterns including modified dietary approach stop hypertension mdash diet modified mediterranean mmed diet incidence btc population based prospective study methods study population comprised 76 014 swedish adults 45 83 years age cancer free baseline mdash mmed diets calculated self reported dietary data collected validated food frequency questionnaire cox proportional hazards regression models used estimate hazard ratios hr 95 confidence intervals ci adjusted potential confounders results 1 010 777 person years mean 13 3 years follow 140 extrahepatic btc cases including 77 gallbladder cancers 23 intrahepatic btc cases ascertained linkage swedish cancer register adherence mdash mmed diets statistically significantly inversely associated risk extrahepatic btc p trend 0 0003 gallbladder cancer p trend 0 005 intrahepatic btc p trend 0 11 multivariable hrs 95 ci highest versus lowest tertile mdash diet 0 41 0 26 0 64 extrahepatic btc 0 36 0 20 0 64 gallbladder cancer corresponding hrs 95 ci mmed diet respectively 0 41 0 25 0 67 0 42 0 23 0 79 conclusion adherence healthy diet may play role reducing risk extrahepatic btc pubmed","probabilities":0.9799733,"Title":"Healthy dietary patterns and incidence of biliary tract and gallbladder cancer in a prospective study of women and men","Abstract":"BACKGROUND: Whether diet influences the risk of biliary tract cancer (BTC) is unknown. We examined the associations of two healthy dietary patterns, including a modified Dietary Approach to Stop Hypertension (mDASH) diet and a modified Mediterranean (mMED) diet, with the incidence of BTC in a population-based prospective study. METHODS: The study population comprised 76,014 Swedish adults who were 45-83 years of age and cancer-free at baseline. The mDASH and mMED diets were calculated from self-reported dietary data collected by a validated food-frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) adjusted for potential confounders. RESULTS: Over 1,010,777 person-years (mean 13.3 years) of follow-up, 140 extrahepatic BTC cases (including 77 gallbladder cancers) and 23 intrahepatic BTC cases were ascertained by linkage with the Swedish Cancer Register. Adherence to the mDASH and mMED diets was statistically significantly inversely associated with risk of extrahepatic BTC (P(trend) ≤ 0.0003) and gallbladder cancer (P(trend) ≤ 0.005) but not intrahepatic BTC (P(trend) ≥ 0.11). The multivariable HRs (95% CI) for the highest versus lowest tertile of the mDASH diet were 0.41 (0.26-0.64) for extrahepatic BTC and 0.36 (0.20-0.64) for gallbladder cancer. The corresponding HRs (95% CI) for the mMED diet were respectively 0.41 (0.25-0.67) and 0.42 (0.23-0.79). CONCLUSION: Adherence to a healthy diet may play a role in reducing the risk of extrahepatic BTC.","Source":"PubMed","category":"HUMAN","training_data":"Healthy dietary patterns and incidence of biliary tract and gallbladder cancer in a prospective study of women and men BACKGROUND: Whether diet influences the risk of biliary tract cancer (BTC) is unknown. We examined the associations of two healthy dietary patterns, including a modified Dietary Approach to Stop Hypertension (mDASH) diet and a modified Mediterranean (mMED) diet, with the incidence of BTC in a population-based prospective study. METHODS: The study population comprised 76,014 Swedish adults who were 45-83 years of age and cancer-free at baseline. The mDASH and mMED diets were calculated from self-reported dietary data collected by a validated food-frequency questionnaire. Cox proportional hazards regression models were used to estimate hazard ratios (HR) with 95% confidence intervals (CI) adjusted for potential confounders. RESULTS: Over 1,010,777 person-years (mean 13.3 years) of follow-up, 140 extrahepatic BTC cases (including 77 gallbladder cancers) and 23 intrahepatic BTC cases were ascertained by linkage with the Swedish Cancer Register. Adherence to the mDASH and mMED diets was statistically significantly inversely associated with risk of extrahepatic BTC (P(trend) ≤ 0.0003) and gallbladder cancer (P(trend) ≤ 0.005) but not intrahepatic BTC (P(trend) ≥ 0.11). The multivariable HRs (95% CI) for the highest versus lowest tertile of the mDASH diet were 0.41 (0.26-0.64) for extrahepatic BTC and 0.36 (0.20-0.64) for gallbladder cancer. The corresponding HRs (95% CI) for the mMED diet were respectively 0.41 (0.25-0.67) and 0.42 (0.23-0.79). CONCLUSION: Adherence to a healthy diet may play a role in reducing the risk of extrahepatic BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"biofilm producing salmonella typhi chronic colonization development gallbladder cancer salmonella enterica subspecies enterica serovar typhi aetiological agent typhoid enteric fever subset individuals typhi colonizes gallbladder causing asymptomatic chronic infection nonetheless asymptomatic carriers provide reservoir spreading disease epidemiological studies performed regions typhi endemic revealed majority chronically infected carriers also harbour gallstones turn indicated primary predisposing factor onset gallbladder cancer gc well recognised typhi produces typhoid toxin carcinogenic potential induces dna damage cell cycle alterations intoxicated cells addition biofilm production typhi may represent key factor promotion persistent infection gallbladder thus sustaining chronic local inflammatory response exposing epithelium repeated damage caused carcinogenic toxins review aims highlight putative connection chronic colonization highly pathogenic strains typhi capable combining biofilm toxin production onset gc considering high risk gc associated asymptomatic carrier status rapid identification profiling biofilm production typhi strains key effective therapeutic management cancer prevention pubmed","probabilities":0.962963,"Title":"Biofilm Producing Salmonella Typhi: Chronic Colonization and Development of Gallbladder Cancer","Abstract":"Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention.","Source":"PubMed","category":"HUMAN","training_data":"Biofilm Producing Salmonella Typhi: Chronic Colonization and Development of Gallbladder Cancer Salmonella enterica subspecies enterica serovar Typhi is the aetiological agent of typhoid or enteric fever. In a subset of individuals, S. Typhi colonizes the gallbladder causing an asymptomatic chronic infection. Nonetheless, these asymptomatic carriers provide a reservoir for further spreading of the disease. Epidemiological studies performed in regions where S. Typhi is endemic, revealed that the majority of chronically infected carriers also harbour gallstones, which in turn, have been indicated as a primary predisposing factor for the onset of gallbladder cancer (GC). It is now well recognised, that S. Typhi produces a typhoid toxin with a carcinogenic potential, that induces DNA damage and cell cycle alterations in intoxicated cells. In addition, biofilm production by S. Typhi may represent a key factor for the promotion of a persistent infection in the gallbladder, thus sustaining a chronic local inflammatory response and exposing the epithelium to repeated damage caused by carcinogenic toxins. This review aims to highlight the putative connection between the chronic colonization by highly pathogenic strains of S. Typhi capable of combining biofilm and toxin production and the onset of GC. Considering the high risk of GC associated with the asymptomatic carrier status, the rapid identification and profiling of biofilm production by S. Typhi strains would be key for effective therapeutic management and cancer prevention. PubMed","prediction_labels":"HUMAN"},{"cleaned":"lymph node status resection gallbladder adenocarcinoma prognostic implications different nodal staging scoring systems background objectives several lymph node ln staging scoring systems proposed stratify prognosis patients gallbladder adenocarcinoma gba sought define prognostic performance commonly utilized ln staging scoring systems including ajcc uicc n stage lymph node ratio lnr log odds lodds n score among patients gba method 2004 2010 1 124 patients gba identified surveillance epidemiology end results seer database discriminative ability ln staging scoring system assessed using akaike information criterion aic harrell concordance index results assessed using categorical values lnr modest improved ability discriminate patients regard prognosis c index 0 615 aic 2118 2 compared ajcc uicc n stage n score prognostic discrimination comparable lodds among patients total number ln examined tnle 1 2 staging scoring systems performed comparably contrast among patients 4 tnle lodds performed best c index 0 613 aic 303 2 conclusion performance different ln staging scoring systems varied based tnle particular patients 4 tnle lodds performed staging scoring systems pubmed","probabilities":0.9799733,"Title":"Lymph node status after resection for gallbladder adenocarcinoma: prognostic implications of different nodal staging/scoring systems","Abstract":"BACKGROUND AND OBJECTIVES: Several lymph node (LN) staging/scoring systems have been proposed to stratify the prognosis of patients with gallbladder adenocarcinoma (GBA). We sought to define the prognostic performance of the most commonly utilized LN staging/scoring systems including AJCC/UICC N stage, lymph node ratio (LNR), log odds (LODDS), and N score, among patients with GBA. METHOD: Between 2004 and 2010, 1,124 patients with GBA were identified from the Surveillance Epidemiology and End Results (SEER) database. The discriminative ability of each LN staging/scoring system was assessed using the Akaike's Information Criterion (AIC) and the Harrell's concordance index. RESULTS: When assessed using categorical values, LNR had a modest, improved ability to discriminate patients with regard to prognosis (C-index: 0.615; AIC: 2118.2) compared with AJCC/UICC N stage or N score and a prognostic discrimination comparable to LODDS. Among patients who had a total number of LN examined (TNLE) of 1 or 2, all the staging/scoring systems performed comparably. In contrast, among patients who had ≥4 TNLE, LODDS performed the best (C-index: 0.613; AIC: 303.2). CONCLUSION: The performance of the different LN staging/scoring systems varied based on the TNLE. In particular, for patients who had ≥4 TNLE, LODDS out-performed the other staging/scoring systems.","Source":"PubMed","category":"HUMAN","training_data":"Lymph node status after resection for gallbladder adenocarcinoma: prognostic implications of different nodal staging/scoring systems BACKGROUND AND OBJECTIVES: Several lymph node (LN) staging/scoring systems have been proposed to stratify the prognosis of patients with gallbladder adenocarcinoma (GBA). We sought to define the prognostic performance of the most commonly utilized LN staging/scoring systems including AJCC/UICC N stage, lymph node ratio (LNR), log odds (LODDS), and N score, among patients with GBA. METHOD: Between 2004 and 2010, 1,124 patients with GBA were identified from the Surveillance Epidemiology and End Results (SEER) database. The discriminative ability of each LN staging/scoring system was assessed using the Akaike's Information Criterion (AIC) and the Harrell's concordance index. RESULTS: When assessed using categorical values, LNR had a modest, improved ability to discriminate patients with regard to prognosis (C-index: 0.615; AIC: 2118.2) compared with AJCC/UICC N stage or N score and a prognostic discrimination comparable to LODDS. Among patients who had a total number of LN examined (TNLE) of 1 or 2, all the staging/scoring systems performed comparably. In contrast, among patients who had ≥4 TNLE, LODDS performed the best (C-index: 0.613; AIC: 303.2). CONCLUSION: The performance of the different LN staging/scoring systems varied based on the TNLE. In particular, for patients who had ≥4 TNLE, LODDS out-performed the other staging/scoring systems. PubMed","prediction_labels":"HUMAN"},{"cleaned":"correlation hmgb1 expression progression poor prognosis adenocarcinoma squamous cell adenosquamous carcinoma gallbladder hmgb1 high mobility group box 1 expressions adenocarcinoma ac squamous cell adenosquamous sc asc carcinoma gallbladder well prognostic significance yet evaluated investigated hmgb1 expression 80 cases ac gallbladder cancer 52 cases sc asc gallbladder cancer survival information concomitantly collected association hmgb1 expression clinicopathological characteristics possible prognostic role hmgb1 two aforementioned subtypes gallbladder cancers also analyzed sirna technique utilized explore role hmgb1 proliferation invasion gallbladder cancer cells vitro hmgb1 overexpression present ac sc asc gallbladder cancers hmgb1 expression significantly associates growth metastasis ac sc asc gallbladder cancers vitro cell experiments based sirna demonstrated hmgb1 downregulation inhibits proliferation invasion gallbladder cancer cells kaplan meier analysis revealed hmgb1 expression negatively associated overall survival time patients ac sc asc gallbladder cancer cox multivariate analysis confirmed hmgb1 independent risk factor survival patients ac sc asc gallbladder cancer hmgb1 overexpression closely correlates progression poor prognosis ac sc asc gallbladder cancers stn","probabilities":0.9467213,"Title":"Correlation Of Hmgb1 Expression To Progression And Poor Prognosis Of Adenocarcinoma And Squamous Cell/Adenosquamous Carcinoma Of Gallbladder","Abstract":"HMGB1 (High mobility group box 1) expressions in adenocarcinoma (AC) and squamous cell/adenosquamous (SC/ASC) carcinoma of gallbladder, as well as its prognostic significance, have not yet been evaluated. We investigated HMGB1 expression in 80 cases of AC gallbladder cancer and 52 cases of SC/ASC gallbladder cancer. Survival information was concomitantly collected. The association of HMGB1 expression with clinicopathological characteristics and the possible prognostic role of HMGB1 for two aforementioned subtypes of gallbladder cancers were also analyzed. siRNA technique was utilized to explore the role of HMGB1 in proliferation and invasion of gallbladder cancer cells in vitro. HMGB1 overexpression is present in AC and SC/ASC gallbladder cancers. HMGB1 expression significantly associates with growth and metastasis of AC and SC/ASC gallbladder cancers. In vitro cell experiments based on siRNA demonstrated that HMGB1 downregulation inhibits proliferation and invasion of gallbladder cancer cells. Kaplan-Meier analysis revealed that HMGB1 expression is negatively associated with overall survival time of patients with AC or SC/ASC gallbladder cancer. Cox multivariate analysis confirmed that HMGB1 is an independent risk factor for survival of patients with AC or SC/ASC gallbladder cancer. HMGB1 overexpression closely correlates with progression and poor prognosis of AC and SC/ASC gallbladder cancers.","Source":"STN","category":"ANIMAL","training_data":"Correlation Of Hmgb1 Expression To Progression And Poor Prognosis Of Adenocarcinoma And Squamous Cell/Adenosquamous Carcinoma Of Gallbladder HMGB1 (High mobility group box 1) expressions in adenocarcinoma (AC) and squamous cell/adenosquamous (SC/ASC) carcinoma of gallbladder, as well as its prognostic significance, have not yet been evaluated. We investigated HMGB1 expression in 80 cases of AC gallbladder cancer and 52 cases of SC/ASC gallbladder cancer. Survival information was concomitantly collected. The association of HMGB1 expression with clinicopathological characteristics and the possible prognostic role of HMGB1 for two aforementioned subtypes of gallbladder cancers were also analyzed. siRNA technique was utilized to explore the role of HMGB1 in proliferation and invasion of gallbladder cancer cells in vitro. HMGB1 overexpression is present in AC and SC/ASC gallbladder cancers. HMGB1 expression significantly associates with growth and metastasis of AC and SC/ASC gallbladder cancers. In vitro cell experiments based on siRNA demonstrated that HMGB1 downregulation inhibits proliferation and invasion of gallbladder cancer cells. Kaplan-Meier analysis revealed that HMGB1 expression is negatively associated with overall survival time of patients with AC or SC/ASC gallbladder cancer. Cox multivariate analysis confirmed that HMGB1 is an independent risk factor for survival of patients with AC or SC/ASC gallbladder cancer. HMGB1 overexpression closely correlates with progression and poor prognosis of AC and SC/ASC gallbladder cancers. STN","prediction_labels":"ANIMAL"},{"cleaned":"second line chemotherapy advanced biliary cancer progressed first line platinum gemcitabine combination multicenter survey pooled analysis published data background progression standard first line platinum gemcitabine combination gp established second line therapy patients advanced biliary tract cancers abtc indeed literature data suggest limited activity second line agents evaluated far methods collected large retrospective series abtc patients treated second line chemotherapy progression first line gp regimen different italian institutions pooled data reported previous studies identified medline search line abstract datasets major international oncology meetings results total 174 patients included multicenter survey response rate rr second line chemotherapy low 3 4 median pfs os 3 0 months 6 6 months respectively multivariate analysis preserved performance status low ca19 9 levels absence distant metastases favorable prognostic factors data five presented published series identified total 499 patients included pooled analysis results confirmed marginal activity second line chemotherapy rr 10 2 limited efficacy unselected patient populations median pfs 3 1 months median os 6 3 months conclusions current analysis highlights limited value second line chemotherapy first line gp combination abtc waiting effective biologic agents setting ongoing randomized trials identify optimal second line chemotherapy regimen validate prognostic factors individual patient management pubmed","probabilities":0.9799733,"Title":"Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data","Abstract":"BACKGROUND: After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far. METHODS: We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings. RESULTS: A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months). CONCLUSIONS: The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.","Source":"PubMed","category":"HUMAN","training_data":"Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data BACKGROUND: After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far. METHODS: We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings. RESULTS: A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months). CONCLUSIONS: The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management. PubMed","prediction_labels":"HUMAN"},{"cleaned":"trends incidence factors affecting survival patients cholangiocarcinoma united states background cholangiocarcinoma cca includes cancers arising intrahepatic extrahepatic bile ducts etiology pathogenesis cca remain poorly understood first study investigating incidence patterns cca 1973 2012 demographic clinical treatment variables affecting survival patients cca patients methods using seer database age adjusted incidence rates evaluated 1973 2012 using seer stat software retrospective cohort 26 994 patients diagnosed cca 1973 2008 identified survival analysis cox proportional hazards models used perform multivariate survival analysis results overall incidence cca increased 65 1973 2012 extrahepatic cca ecc remained common intrahepatic cca icc whereas incidence rates icc increased 350 compared 20 increase seen ecc men belonging non african american non caucasian ethnicities highest incidence rates cca trend persisted throughout study period although african americans caucasians saw 50 59 increases incidence rates respectively compared 9 increase among races median overall survival os 8 months patients ecc compared 4 months icc survival analysis found hispanic women best 5 year survival outcome p 0001 os diminished age p 0001 ecc better survival outcomes compared icc p 0001 patients married nonsmokers belonged higher income class underwent surgery better survival outcomes compared others p 0001 conclusions date study cca seer registry shows temporal patterns increasing incidence cca across different races sexes ethnicities identified age sex race marital status income smoking status anatomic location cca tumor grade tumor stage radiation surgery independent prognostic factors os patients cca pubmed","probabilities":0.9799733,"Title":"Trends in Incidence and Factors Affecting Survival of Patients With Cholangiocarcinoma in the United States","Abstract":"Background: Cholangiocarcinoma (CCA) includes cancers arising from the intrahepatic and extrahepatic bile ducts. The etiology and pathogenesis of CCA remain poorly understood. This is the first study investigating both incidence patterns of CCA from 1973 through 2012 and demographic, clinical, and treatment variables affecting survival of patients with CCA. Patients and Methods: Using the SEER database, age-adjusted incidence rates were evaluated from 1973-2012 using SEER*Stat software. A retrospective cohort of 26,994 patients diagnosed with CCA from 1973-2008 was identified for survival analysis. Cox proportional hazards models were used to perform multivariate survival analysis. Results: Overall incidence of CCA increased by 65% from 1973-2012. Extrahepatic CCA (ECC) remained more common than intrahepatic CCA (ICC), whereas the incidence rates for ICC increased by 350% compared with a 20% increase seen with ECC. Men belonging to non-African American and non-Caucasian ethnicities had the highest incidence rates of CCA. This trend persisted throughout the study period, although African Americans and Caucasians saw 50% and 59% increases in incidence rates, respectively, compared with a 9% increase among other races. Median overall survival (OS) was 8 months in patients with ECC compared with 4 months in those with ICC. Our survival analysis found Hispanic women to have the best 5-year survival outcome (P<.0001). OS diminished with age (P<.0001), and ECC had better survival outcomes compared with ICC (P<.0001). Patients who were married, were nonsmokers, belonged to a higher income class, and underwent surgery had better survival outcomes compared with others (P<.0001). Conclusions: This is the most up-to-date study of CCA from the SEER registry that shows temporal patterns of increasing incidence of CCA across different races, sexes, and ethnicities. We identified age, sex, race, marital status, income, smoking status, anatomic location of CCA, tumor grade, tumor stage, radiation, and surgery as independent prognostic factors for OS in patients with CCA.","Source":"PubMed","category":"HUMAN","training_data":"Trends in Incidence and Factors Affecting Survival of Patients With Cholangiocarcinoma in the United States Background: Cholangiocarcinoma (CCA) includes cancers arising from the intrahepatic and extrahepatic bile ducts. The etiology and pathogenesis of CCA remain poorly understood. This is the first study investigating both incidence patterns of CCA from 1973 through 2012 and demographic, clinical, and treatment variables affecting survival of patients with CCA. Patients and Methods: Using the SEER database, age-adjusted incidence rates were evaluated from 1973-2012 using SEER*Stat software. A retrospective cohort of 26,994 patients diagnosed with CCA from 1973-2008 was identified for survival analysis. Cox proportional hazards models were used to perform multivariate survival analysis. Results: Overall incidence of CCA increased by 65% from 1973-2012. Extrahepatic CCA (ECC) remained more common than intrahepatic CCA (ICC), whereas the incidence rates for ICC increased by 350% compared with a 20% increase seen with ECC. Men belonging to non-African American and non-Caucasian ethnicities had the highest incidence rates of CCA. This trend persisted throughout the study period, although African Americans and Caucasians saw 50% and 59% increases in incidence rates, respectively, compared with a 9% increase among other races. Median overall survival (OS) was 8 months in patients with ECC compared with 4 months in those with ICC. Our survival analysis found Hispanic women to have the best 5-year survival outcome (P<.0001). OS diminished with age (P<.0001), and ECC had better survival outcomes compared with ICC (P<.0001). Patients who were married, were nonsmokers, belonged to a higher income class, and underwent surgery had better survival outcomes compared with others (P<.0001). Conclusions: This is the most up-to-date study of CCA from the SEER registry that shows temporal patterns of increasing incidence of CCA across different races, sexes, and ethnicities. We identified age, sex, race, marital status, income, smoking status, anatomic location of CCA, tumor grade, tumor stage, radiation, and surgery as independent prognostic factors for OS in patients with CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role surgery treatment intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc second common primary liver cancer accounting 10 15 primary hepatic malignancy incidence increasing western countries surgery curative intent treatment offers chance long term survival reported 5 year overall survival rate ranging 17 48 recent series postoperative mortality lower 5 morbidity varied 6 66 macroscopic classification icc proposed liver cancer study group japan lcsgj reflects different biologic behaviours pattern tumor growth clinicopathological findings important prognostic factors resection positive resection margins lymph node metastases tumor size presence macrovascular invasion intrahepatic metastases unfortunately recurrence still frequent leading cause death treatment recurrence varied according location extension disease recently expression several genes found related carcinogenesis icc molecular findings helpful differentiate biological behaviour provide evidence development new target therapies pubmed","probabilities":0.9799733,"Title":"Role of surgery in the treatment of intrahepatic cholangiocarcinoma","Abstract":"Intrahepatic Cholangiocarcinoma (ICC) is the second most common primary liver cancer, accounting for 10% to 15% of primary hepatic malignancy, and its incidence is increasing in Western Countries. Surgery with curative intent is the only treatment that offers a chance of long-term survival, with a reported 5-year overall survival rate ranging from 17% to 48%. In the most of recent series postoperative mortality is lower than 5% and morbidity varied from 6% to 66%. The macroscopic classification of ICC, proposed by Liver Cancer Study Group of Japan (LCSGJ), reflects different biologic behaviours, pattern of tumor growth and clinicopathological findings. The most important prognostic factors after resection are positive resection margins, lymph-node metastases, tumor size, presence of macrovascular invasion and intrahepatic metastases. Unfortunately, recurrence is still frequent and it is the leading cause of death. The treatment of the recurrence varied according to the location and extension of the disease. Recently, expression of several genes found to be related with the carcinogenesis of ICC. These molecular findings are helpful to differentiate the biological behaviour and will provide evidence for the development of new target therapies.","Source":"PubMed","category":"HUMAN","training_data":"Role of surgery in the treatment of intrahepatic cholangiocarcinoma Intrahepatic Cholangiocarcinoma (ICC) is the second most common primary liver cancer, accounting for 10% to 15% of primary hepatic malignancy, and its incidence is increasing in Western Countries. Surgery with curative intent is the only treatment that offers a chance of long-term survival, with a reported 5-year overall survival rate ranging from 17% to 48%. In the most of recent series postoperative mortality is lower than 5% and morbidity varied from 6% to 66%. The macroscopic classification of ICC, proposed by Liver Cancer Study Group of Japan (LCSGJ), reflects different biologic behaviours, pattern of tumor growth and clinicopathological findings. The most important prognostic factors after resection are positive resection margins, lymph-node metastases, tumor size, presence of macrovascular invasion and intrahepatic metastases. Unfortunately, recurrence is still frequent and it is the leading cause of death. The treatment of the recurrence varied according to the location and extension of the disease. Recently, expression of several genes found to be related with the carcinogenesis of ICC. These molecular findings are helpful to differentiate the biological behaviour and will provide evidence for the development of new target therapies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact worldwide national sub national severity distributions burden disease studies case study cancers scotland background increasingly burden disease bod measures used influence policy decisions summarise complete effects morbidity mortality equitable manner important element producing non fatal bod estimates severity distributions global burden disease gbd study use severity distributions across countries due lack available country specific data scottish bod sbod study developed national severity distributions cancer types main aim study consider extent use worldwide severity distributions bod studies influencing cross country comparisons comparing weighted average disability weights dw based gbd severity distributions nationally derived severity distributions scotland cancer types methods obtained individual records scottish cancer registry 21 cancer types linked registered deaths estimated prevalent cancer cases 2016 assigned case sequelae using gbd 2016 study definitions compared impact using severity distributions based gbd 2016 scotland wide distribution distributions specific deprivation strata scotland weighted average dw cancer type results relative difference point estimates weighted average dw based gbd 2016 worldwide severity distributions compared scottish national severity distributions resulted overestimates majority cancers 17 21 cancer types largest overestimates gallbladder biliary tract cancer 70 8 oesophageal cancer 31 6 pancreatic cancer 31 2 furthermore use weighted average dw based scottish national severity distributions rather sub national scottish severity distributions stratified deprivation quintile overestimated weighted average dw least deprived areas 16 18 cancer types underestimated deprived areas 16 18 cancer types conclusion findings illustrate bias point estimates weighted average dw created using worldwide severity distributions bias led misrepresentation non fatal estimates burden individual cancers underestimated scale socioeconomic inequality non fatal burden highlights importance interpreting non fatal estimates burden disease precisely especially sub national estimates comparing populations relying data inputs countries essential ensure estimates based upon country specific data far possible pubmed","probabilities":0.9799733,"Title":"The impact of worldwide, national and sub-national severity distributions in Burden of Disease studies: A case study of cancers in Scotland","Abstract":"BACKGROUND: Increasingly Burden of Disease (BOD) measures are being used to influence policy decisions because they summarise the complete effects of morbidity and mortality in an equitable manner. An important element of producing non-fatal BOD estimates are severity distributions. The Global Burden of Disease (GBD) study use the same severity distributions across countries due to a lack of available country-specific data. In the Scottish BOD (SBOD) study we developed national severity distributions for cancer types. The main aim of this study was to consider the extent to which the use of worldwide severity distributions in BOD studies are influencing cross-country comparisons, by comparing weighted-average disability weights (DW) based on GBD severity distributions with nationally derived severity distributions in Scotland for cancer types. METHODS: We obtained individual records from the Scottish Cancer Registry for 21 cancer types and linked these to registered deaths. We estimated prevalent cancer cases for 2016 and assigned each case to sequelae using GBD 2016 study definitions. We compared the impact of using severity distributions based on GBD 2016, a Scotland-wide distribution, and distributions specific to deprivation strata in Scotland, on the weighted-average DW for each cancer type. RESULTS: The relative difference in point estimates of weighted-average DW based on GBD 2016 worldwide severity distributions compared with Scottish national severity distributions resulted in overestimates in the majority of cancers (17 out of 21 cancer types). The largest overestimates were for gallbladder and biliary tract cancer (70.8%), oesophageal cancer (31.6%) and pancreatic cancer (31.2%). Furthermore, the use of weighted-average DW based on Scottish national severity distributions rather than sub-national Scottish severity distributions stratified by deprivation quintile overestimated weighted-average DW in the least deprived areas (16 out of 18 cancer types), and underestimated in the most deprived areas (16 out of 18 cancer types). CONCLUSION: Our findings illustrate a bias in point estimates of weighted-average DW created using worldwide severity distributions. This bias would have led to the misrepresentation of non-fatal estimates of the burden of individual cancers, and underestimated the scale of socioeconomic inequality in this non-fatal burden. This highlights the importance of not interpreting non-fatal estimates of burden of disease too precisely, especially for sub-national estimates and those comparing populations when relying on data inputs from other countries. It is essential to ensure that any estimates are based upon country-specific data as far as possible.","Source":"PubMed","category":"HUMAN","training_data":"The impact of worldwide, national and sub-national severity distributions in Burden of Disease studies: A case study of cancers in Scotland BACKGROUND: Increasingly Burden of Disease (BOD) measures are being used to influence policy decisions because they summarise the complete effects of morbidity and mortality in an equitable manner. An important element of producing non-fatal BOD estimates are severity distributions. The Global Burden of Disease (GBD) study use the same severity distributions across countries due to a lack of available country-specific data. In the Scottish BOD (SBOD) study we developed national severity distributions for cancer types. The main aim of this study was to consider the extent to which the use of worldwide severity distributions in BOD studies are influencing cross-country comparisons, by comparing weighted-average disability weights (DW) based on GBD severity distributions with nationally derived severity distributions in Scotland for cancer types. METHODS: We obtained individual records from the Scottish Cancer Registry for 21 cancer types and linked these to registered deaths. We estimated prevalent cancer cases for 2016 and assigned each case to sequelae using GBD 2016 study definitions. We compared the impact of using severity distributions based on GBD 2016, a Scotland-wide distribution, and distributions specific to deprivation strata in Scotland, on the weighted-average DW for each cancer type. RESULTS: The relative difference in point estimates of weighted-average DW based on GBD 2016 worldwide severity distributions compared with Scottish national severity distributions resulted in overestimates in the majority of cancers (17 out of 21 cancer types). The largest overestimates were for gallbladder and biliary tract cancer (70.8%), oesophageal cancer (31.6%) and pancreatic cancer (31.2%). Furthermore, the use of weighted-average DW based on Scottish national severity distributions rather than sub-national Scottish severity distributions stratified by deprivation quintile overestimated weighted-average DW in the least deprived areas (16 out of 18 cancer types), and underestimated in the most deprived areas (16 out of 18 cancer types). CONCLUSION: Our findings illustrate a bias in point estimates of weighted-average DW created using worldwide severity distributions. This bias would have led to the misrepresentation of non-fatal estimates of the burden of individual cancers, and underestimated the scale of socioeconomic inequality in this non-fatal burden. This highlights the importance of not interpreting non-fatal estimates of burden of disease too precisely, especially for sub-national estimates and those comparing populations when relying on data inputs from other countries. It is essential to ensure that any estimates are based upon country-specific data as far as possible. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumor suppressor lkb1 inhibits progression gallbladder carcinoma predicts prognosis patients malignancy gallbladder carcinoma gbc represents common fatal tumors biliary tract 3 year 5 year survival rate patients disease 30 5 respectively liver kinase b1 lkb1 primary upstream kinase adenosine monophosphate activated protein kinase ampk necessary maintaining cell metabolism energy homeostasis found important tumor suppressor gene recent years inactivation also found closely associated tumor growth metastasis cancer stem cell csc proliferation nevertheless function lkb1 gbc remains unclear study found expression lkb1 gbc tissues decreased compared non cancerous tissues lkb1 overexpression suppressed proliferation metastasis expansion gbc cscs mechanically lkb1 suppressed gbc cell progression via jak signal transducer activator transcription 3 stat3 pathway use jak2 inhibitor azd 1480 attenuated suppressive effects lkb1 overexpression growth metastasis self renewal ability gbc cells demonstrated jak stat3 involved lkb1 induced suppression gbc cell growth metastasis self renewal ability importantly decreased expression lkb1 predictor poor prognosis patients gbc whole data indicate lkb1 inhibits gbc cell growth metastasis self renewal ability disrupting jak stat3 signaling may thus prove novel prognostic biomarker patients gbc pubmed","probabilities":0.962963,"Title":"Tumor suppressor LKB1 inhibits the progression of gallbladder carcinoma and predicts the prognosis of patients with this malignancy","Abstract":"Gallbladder carcinoma (GBC) represents the most common fatal tumors of the biliary tract. The 3-year or 5-year survival rate for patients with this disease are 30 and 5%, respectively. Liver kinase B1 (LKB1), a primary upstream kinase of adenosine monophosphate-activated protein kinase (AMPK) necessary for maintaining cell metabolism and energy homeostasis, has been found to be an important tumor suppressor gene in recent years, and its inactivation has also found to be closely associated with tumor growth, metastasis and cancer stem cell (CSC) proliferation. Nevertheless, the function of LKB1 in GBC remains unclear. In this study, we found that the expression of LKB1 in GBC tissues was decreased compared with that in non-cancerous tissues. LKB1 overexpression suppressed the proliferation, metastasis and expansion of GBC CSCs. Mechanically, LKB1 suppressed GBC cell progression via the JAK/signal transducer and activator of transcription 3 (STAT3) pathway. The use of the JAK2 inhibitor, AZD‑1480, attenuated the suppressive effects of LKB1 overexpression on the growth, metastasis and self-renewal ability of the GBC cells, which further demonstrated that JAK/STAT3 was involved in the LKB1-induced suppression of GBC cell growth, metastasis and self-renewal ability. More importantly, the decreased expression of LKB1 was a predictor of a poor prognosis of patients with GBC. On the whole, our data indicate that LKB1 inhibits GBC cell growth, metastasis and self-renewal ability by disrupting JAK/STAT3 signaling, and may thus prove to be a novel prognostic biomarker for patients with GBC.","Source":"PubMed","category":"HUMAN","training_data":"Tumor suppressor LKB1 inhibits the progression of gallbladder carcinoma and predicts the prognosis of patients with this malignancy Gallbladder carcinoma (GBC) represents the most common fatal tumors of the biliary tract. The 3-year or 5-year survival rate for patients with this disease are 30 and 5%, respectively. Liver kinase B1 (LKB1), a primary upstream kinase of adenosine monophosphate-activated protein kinase (AMPK) necessary for maintaining cell metabolism and energy homeostasis, has been found to be an important tumor suppressor gene in recent years, and its inactivation has also found to be closely associated with tumor growth, metastasis and cancer stem cell (CSC) proliferation. Nevertheless, the function of LKB1 in GBC remains unclear. In this study, we found that the expression of LKB1 in GBC tissues was decreased compared with that in non-cancerous tissues. LKB1 overexpression suppressed the proliferation, metastasis and expansion of GBC CSCs. Mechanically, LKB1 suppressed GBC cell progression via the JAK/signal transducer and activator of transcription 3 (STAT3) pathway. The use of the JAK2 inhibitor, AZD‑1480, attenuated the suppressive effects of LKB1 overexpression on the growth, metastasis and self-renewal ability of the GBC cells, which further demonstrated that JAK/STAT3 was involved in the LKB1-induced suppression of GBC cell growth, metastasis and self-renewal ability. More importantly, the decreased expression of LKB1 was a predictor of a poor prognosis of patients with GBC. On the whole, our data indicate that LKB1 inhibits GBC cell growth, metastasis and self-renewal ability by disrupting JAK/STAT3 signaling, and may thus prove to be a novel prognostic biomarker for patients with GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"consumption soft drinks juices risk liver biliary tract cancers european cohort purpose aim study assess associations intake combined soft drinks sugar sweetened artificially sweetened fruit vegetable juices risk hepatocellular carcinoma hcc intrahepatic bile duct ihbc biliary tract cancers gbtc using data european prospective investigation cancer nutrition cohort 477 206 participants 10 european countries methods 11 4 years follow 191 hcc 66 ihbc 236 gbtc cases identified hazard ratios 95 confidence intervals hr 95 ci estimated cox regression models multivariable adjustment baseline total energy intake alcohol consumption intake pattern body mass index physical activity level educational attainment self reported diabetes status results risk associations observed ihbc gbtc combined soft drinks consumption 6 servings week positively associated hcc risk hr 1 83 95 ci 1 11 3 02 p trend 0 01 versus non consumers sub group analyses available 91 cohort artificially sweetened soft drinks increased hcc risk 6 per 1 serving increment hr 1 06 95 ci 1 03 1 09 n cases 101 sugar sweetened soft drinks association null hr 1 00 95 ci 0 95 1 06 n cases 127 p heterogeneity 0 07 juice consumption associated hcc risk except low intakes 1 serving week hr 0 60 95 ci 0 38 0 95 p trend 0 02 vs non consumers conclusions daily intake combined soft drinks positively associated hcc differential association sugar artificially sweetened discounted study provides insight possible associations hcc sugary drinks intake exploration settings required pubmed","probabilities":0.9799733,"Title":"Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort","Abstract":"PURPOSE: The aim of the study was to assess associations between intake of combined soft drinks (sugar sweetened and artificially sweetened) and fruit and vegetable juices and the risk of hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBC) and biliary tract cancers (GBTC) using data from the European Prospective Investigation into Cancer and Nutrition cohort of 477,206 participants from 10 European countries. METHODS: After 11.4 years of follow-up, 191 HCC, 66 IHBC and 236 GBTC cases were identified. Hazard ratios and 95% confidence intervals (HR; 95% CI) were estimated with Cox regression models with multivariable adjustment (baseline total energy intake, alcohol consumption and intake pattern, body mass index, physical activity, level of educational attainment and self-reported diabetes status). RESULTS: No risk associations were observed for IHBC or GBTC. Combined soft drinks consumption of >6 servings/week was positively associated with HCC risk: HR 1.83; 95% CI 1.11-3.02, p trend = 0.01 versus non-consumers. In sub-group analyses available for 91% of the cohort artificially sweetened soft drinks increased HCC risk by 6% per 1 serving increment (HR 1.06, 95% CI 1.03-1.09, n cases = 101); for sugar-sweetened soft drinks, this association was null (HR 1.00, 95% CI 0.95-1.06; n cases = 127, p heterogeneity = 0.07). Juice consumption was not associated with HCC risk, except at very low intakes (<1 serving/week: HR 0.60; 95% CI 0.38-0.95; p trend = 0.02 vs. non-consumers). CONCLUSIONS: Daily intake of combined soft drinks is positively associated with HCC, but a differential association between sugar and artificially sweetened cannot be discounted. This study provides some insight into possible associations of HCC with sugary drinks intake. Further exploration in other settings is required.","Source":"PubMed","category":"HUMAN","training_data":"Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort PURPOSE: The aim of the study was to assess associations between intake of combined soft drinks (sugar sweetened and artificially sweetened) and fruit and vegetable juices and the risk of hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBC) and biliary tract cancers (GBTC) using data from the European Prospective Investigation into Cancer and Nutrition cohort of 477,206 participants from 10 European countries. METHODS: After 11.4 years of follow-up, 191 HCC, 66 IHBC and 236 GBTC cases were identified. Hazard ratios and 95% confidence intervals (HR; 95% CI) were estimated with Cox regression models with multivariable adjustment (baseline total energy intake, alcohol consumption and intake pattern, body mass index, physical activity, level of educational attainment and self-reported diabetes status). RESULTS: No risk associations were observed for IHBC or GBTC. Combined soft drinks consumption of >6 servings/week was positively associated with HCC risk: HR 1.83; 95% CI 1.11-3.02, p trend = 0.01 versus non-consumers. In sub-group analyses available for 91% of the cohort artificially sweetened soft drinks increased HCC risk by 6% per 1 serving increment (HR 1.06, 95% CI 1.03-1.09, n cases = 101); for sugar-sweetened soft drinks, this association was null (HR 1.00, 95% CI 0.95-1.06; n cases = 127, p heterogeneity = 0.07). Juice consumption was not associated with HCC risk, except at very low intakes (<1 serving/week: HR 0.60; 95% CI 0.38-0.95; p trend = 0.02 vs. non-consumers). CONCLUSIONS: Daily intake of combined soft drinks is positively associated with HCC, but a differential association between sugar and artificially sweetened cannot be discounted. This study provides some insight into possible associations of HCC with sugary drinks intake. Further exploration in other settings is required. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intra arterial yttrium 90 radioembolization combined systemic chemotherapy promising method downstaging unresectable huge intrahepatic cholangiocarcinoma surgical treatment purpose evaluate downstaging efficacy yttrium 90 radioembolization ytt 90 associated chemotherapy results surgery initially unresectable huge intrahepatic cholangiocarcinoma icc methods january 2008 october 2013 unresectable icc treated chemotherapy ytt 90 patients unique tumors localized noncirrhotic livers without extrahepatic metastasis considered potentially resectable evaluated every 2 months possible secondary resection results forty five patients treated unresectable iccs ten potentially resectable tumors eight underwent surgery initial unresectability due involvement hepatic veins portal vein future liver remnant seven one cases respectively preoperative treatment induced significant decreases tumor volume 295 vs 168 ml p 0 02 allowed r0 resection cases three patients 37 5 clavien dindo grade three higher complications including two postoperative deaths median follow ups 15 6 range 4 40 7 months medical treatment initiation 7 2 0 13 36 4 months surgery end study period five patients still alive one patient still alive 40 months medical treatment initiation 36 4 months surgery two patients experienced recurrences conclusions initially unresectable huge iccs chemotherapy ytt 90 radioembolization effective downstaging method allows secondary resectability pubmed","probabilities":0.9799733,"Title":"Intra-arterial yttrium-90 radioembolization combined with systemic chemotherapy is a promising method for downstaging unresectable huge intrahepatic cholangiocarcinoma to surgical treatment","Abstract":"PURPOSE: To evaluate the downstaging efficacy of yttrium-90 radioembolization (Ytt-90)-associated with chemotherapy and the results of surgery for initially unresectable huge intrahepatic cholangiocarcinoma (ICC). METHODS: Between January 2008 and October 2013, unresectable ICC were treated with chemotherapy and Ytt-90. Patients with unique tumors localized to noncirrhotic livers and without extrahepatic metastasis were considered to be potentially resectable and were evaluated every 2 months for possible secondary resection. RESULTS: Forty-five patients were treated for unresectable ICCs; ten had potentially resectable tumors, and eight underwent surgery. Initial unresectability was due to the involvement of the hepatic veins or portal vein of the future liver remnant in seven and one cases, respectively. Preoperative treatment induced significant decreases in tumor volume (295 vs. 168 ml, p = 0.02) and allowed for R0 resection in all cases. Three patients (37.5 %) had Clavien-Dindo grade three or higher complications, including two postoperative deaths. The median follow-ups were 15.6 [range 4-40.7] months after medical treatment initiation and 7.2 [0.13-36.4] months after surgery. At the end of the study period, five patients were still alive, with one patient still alive 40 months after medical treatment initiation (36.4 months after surgery); two patients experienced recurrences. CONCLUSIONS: For initially unresectable huge ICCs, chemotherapy with Ytt-90 radioembolization is an effective downstaging method that allows for secondary resectability.","Source":"PubMed","category":"HUMAN","training_data":"Intra-arterial yttrium-90 radioembolization combined with systemic chemotherapy is a promising method for downstaging unresectable huge intrahepatic cholangiocarcinoma to surgical treatment PURPOSE: To evaluate the downstaging efficacy of yttrium-90 radioembolization (Ytt-90)-associated with chemotherapy and the results of surgery for initially unresectable huge intrahepatic cholangiocarcinoma (ICC). METHODS: Between January 2008 and October 2013, unresectable ICC were treated with chemotherapy and Ytt-90. Patients with unique tumors localized to noncirrhotic livers and without extrahepatic metastasis were considered to be potentially resectable and were evaluated every 2 months for possible secondary resection. RESULTS: Forty-five patients were treated for unresectable ICCs; ten had potentially resectable tumors, and eight underwent surgery. Initial unresectability was due to the involvement of the hepatic veins or portal vein of the future liver remnant in seven and one cases, respectively. Preoperative treatment induced significant decreases in tumor volume (295 vs. 168 ml, p = 0.02) and allowed for R0 resection in all cases. Three patients (37.5 %) had Clavien-Dindo grade three or higher complications, including two postoperative deaths. The median follow-ups were 15.6 [range 4-40.7] months after medical treatment initiation and 7.2 [0.13-36.4] months after surgery. At the end of the study period, five patients were still alive, with one patient still alive 40 months after medical treatment initiation (36.4 months after surgery); two patients experienced recurrences. CONCLUSIONS: For initially unresectable huge ICCs, chemotherapy with Ytt-90 radioembolization is an effective downstaging method that allows for secondary resectability. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression heat shock protein gp96 gallbladder cancer prognostic clinical significance purpose detect expression prognostic clinical significance heat shock protein gp96 hsp gp96 gallbladder cancer methods immunohistochemistry used detect compare rate hsp gp96 expression 107 samples gallbladder cancer 70 gallbladder adenoma 67 chronic cholecystitis association clinicopathological factors patients survival calculated univariate multivariate cox proportional hazard regression method analysis results expression positive rate hsp gp96 90 7 97 107 gallbladder cancer 71 4 50 70 gallbladder adenoma 47 76 32 67 chronic cholecystitis respectively positive rate hsp gp96 gallbladder cancer tissues significantly higher gallbladder adenoma chronic cholecystitis tissues p 0 01 multivariate cox regression analysis showed positive hsp gp96 p 0 026 expression independent poor prognostic predictor gallbladder cancer conclusions hsp gp96 positive expression closely correlated poor survival gallbladder cancer stn","probabilities":0.7777778,"Title":"Expression Of Heat-Shock Protein Gp96 In Gallbladder Cancer And Its Prognostic Clinical Significance","Abstract":"Purpose: To detect the expression and prognostic clinical significance of heat-shock protein gp96 (HSP gp96) in gallbladder cancer. \r\n\r\n Methods: Immunohistochemistry was used to detect and compare the rate of HSP gp96 expression in 107 samples of gallbladder cancer, 70 of gallbladder adenoma and 67 of chronic cholecystitis. The association of clinicopathological factors and patients' survival were calculated by univariate and multivariate (Cox proportional hazard regression method) analysis. \r\n\r\n Results: The expression positive rate of HSP gp96 was 90.7% (97/107) in gallbladder cancer, 71.4% (50/70) in gallbladder adenoma and 47.76% (32/67) in chronic cholecystitis respectively. The positive rate of HSP gp96 in gallbladder cancer tissues was significantly higher than that in gallbladder adenoma and chronic cholecystitis tissues (P < 0.01). Multivariate and Cox regression analysis showed that positive of HSP gp96 (P = 0.026) expression was an independent poor prognostic predictor in gallbladder cancer. \r\n\r\n Conclusions: HSP gp96-positive expression is closely correlated with poor survival in gallbladder cancer.","Source":"STN","category":"ANIMAL","training_data":"Expression Of Heat-Shock Protein Gp96 In Gallbladder Cancer And Its Prognostic Clinical Significance Purpose: To detect the expression and prognostic clinical significance of heat-shock protein gp96 (HSP gp96) in gallbladder cancer. \r\n\r\n Methods: Immunohistochemistry was used to detect and compare the rate of HSP gp96 expression in 107 samples of gallbladder cancer, 70 of gallbladder adenoma and 67 of chronic cholecystitis. The association of clinicopathological factors and patients' survival were calculated by univariate and multivariate (Cox proportional hazard regression method) analysis. \r\n\r\n Results: The expression positive rate of HSP gp96 was 90.7% (97/107) in gallbladder cancer, 71.4% (50/70) in gallbladder adenoma and 47.76% (32/67) in chronic cholecystitis respectively. The positive rate of HSP gp96 in gallbladder cancer tissues was significantly higher than that in gallbladder adenoma and chronic cholecystitis tissues (P < 0.01). Multivariate and Cox regression analysis showed that positive of HSP gp96 (P = 0.026) expression was an independent poor prognostic predictor in gallbladder cancer. \r\n\r\n Conclusions: HSP gp96-positive expression is closely correlated with poor survival in gallbladder cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"albumin alkaline phosphatase ratio novel prognostic index overall survival cholangiocarcinoma patients surgery aim clarify prognostic significance preoperative albumin alkaline phosphatase ratio aapr cholangiocarcinoma cca subjects receiving surgery methods retrospective study included 303 cca patients receiving surgery without preoperative therapy 2002 2014 clinicopathological characteristics including aapr analyzed determine predictors post operative overall survival recurrence free survival rfs addition univariate multivariate cox proportional hazards models conducted followed application time dependent receiver operating curves identify optimal cut results univariate multivariate analyses revealed decreased overall survival hazard ratio hr 2 88 95 ci 1 19 5 78 recurrence free survival hr 2 31 95 ci 1 40 3 29 patients aapr 0 41 compared aapr 0 41 optimal cut aapr 0 41 303 subjects 253 83 5 aapr 0 41 overall 1 3 5 year survival rates 70 2 38 0 16 5 respectively low 0 41 aapr group significantly lower high 0 41 aapr group 81 7 53 9 33 4 respectively p 0 0001 large tumor size multiple tumors advanced clinical stage also identified significant predictors poor prognosis conclusion outcomes showed aapr potential valuable prognostic indicator cca patients undergoing surgery confirmed prospective studies moreover necessary investigate mechanisms concerning correlation low aapr poor post operative survival cca patients stn","probabilities":0.9799733,"Title":"Albumin-To-Alkaline Phosphatase Ratio: A Novel Prognostic Index Of Overall Survival In Cholangiocarcinoma Patients After Surgery","Abstract":"Aim: To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in cholangiocarcinoma (CCA) subjects receiving surgery. \n\n Methods: In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics (including AAPR) were analyzed to determine predictors of post-operative overall survival and recurrence-free survival (RFS). In addition, univariate and multivariate Cox proportional hazards models were conducted, followed by application of time-dependent receiver operating curves to identify the optimal cut-off. \n\n Results: Univariate and multivariate analyses revealed both decreased overall survival [hazard ratio (HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival (HR: 2.31, 95%CI: 1.40-3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥ 0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253 (83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low (< 0.41) AAPR group, which were significantly lower than those in the high (≥ 0.41) AAPR group (81.7%, 53.9%, and 33.4%, respectively) (P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis. \n\n Conclusion: Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients.","Source":"STN","category":"HUMAN","training_data":"Albumin-To-Alkaline Phosphatase Ratio: A Novel Prognostic Index Of Overall Survival In Cholangiocarcinoma Patients After Surgery Aim: To clarify the prognostic significance of preoperative albumin-to-alkaline phosphatase ratio (AAPR) in cholangiocarcinoma (CCA) subjects receiving surgery. \n\n Methods: In this retrospective study, we included 303 CCA patients receiving surgery without preoperative therapy between 2002 and 2014. Clinicopathological characteristics (including AAPR) were analyzed to determine predictors of post-operative overall survival and recurrence-free survival (RFS). In addition, univariate and multivariate Cox proportional hazards models were conducted, followed by application of time-dependent receiver operating curves to identify the optimal cut-off. \n\n Results: Univariate and multivariate analyses revealed both decreased overall survival [hazard ratio (HR): 2.88, 95%CI: 1.19-5.78] and recurrence-free survival (HR: 2.31, 95%CI: 1.40-3.29) in patients with AAPR < 0.41 compared to those with AAPR ≥ 0.41. The optimal cut-off of AAPR was 0.41. Of the 303 subjects, 253 (83.5%) had an AAPR over 0.41. The overall 1-, 3- and 5-year survival rates were 70.2%, 38.0% and 16.5%, respectively in the low (< 0.41) AAPR group, which were significantly lower than those in the high (≥ 0.41) AAPR group (81.7%, 53.9%, and 33.4%, respectively) (P < 0.0001). Large tumor size, multiple tumors, and advanced clinical stage were also identified as significant predictors of poor prognosis. \n\n Conclusion: Our outcomes showed that AAPR was a potential valuable prognostic indicator in CCA patients undergoing surgery, which should be further confirmed by prospective studies. Moreover, it is necessary to investigate the mechanisms concerning the correlation of low AAPR with poor post-operative survival in CCA patients. STN","prediction_labels":"HUMAN"},{"cleaned":"unresectable intrahepatic cholangiocarcinoma multiparametric mr imaging predict patient survival purpose determine performance magnetic resonance mr imaging based tumor metrics evaluation response transarterial chemoembolization tace patients unresectable intrahepatic cholangiocarcinoma icca materials methods ninety four patients unresectable icca underwent baseline follow mr imaging tace followed death end study duration lesions analyzed anatomic response evaluation criteria solid tumors recist tumor volume functional viable tumor volume viable tumor burden apparent diffusion coefficient adc volumetric mr parameters using semiautomatic software response assessed using changes viable tumor volume using modified recist mrecist derived thresholds three dimensional mrecist viable tumor burden adc overall survival primary endpoint cox regression kaplan meier survival analysis used results tumor volume change tace p 07 whereas recist diameter showed small change 2 6 p 02 increase adc 20 7 decrease viable tumor volume 29 3 viable tumor burden 29 1 p 001 higher overall survival noted among responders using thresholds 25 increase adc 66 decrease viable tumor volume 50 decrease viable tumor burden log rank test p 05 hazard ratio nonresponders using adc three dimensional mrecist viable tumor burden multivariable analysis 2 9 p 004 4 1 p 009 4 0 p 002 respectively survival differences noted patients showed response using three parameters adc three dimensional mrecist viable tumor burden versus showed response using either one two parameters versus showed response p 001 conclusion changes volumetric adc viable tumor volume viable tumor burden mr imaging provide prognostic information among patients unresectable icca undergo tace rsna 2018 online supplemental material available article pubmed","probabilities":0.9799733,"Title":"Unresectable Intrahepatic Cholangiocarcinoma: Multiparametric MR Imaging to Predict Patient Survival","Abstract":"Purpose To determine the performance of magnetic resonance (MR) imaging-based tumor metrics for evaluation of response to transarterial chemoembolization (TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICCA). Materials and Methods Ninety-four patients with unresectable ICCA underwent baseline and follow-up MR imaging after TACE and were followed up until death or end of study duration. Lesions were analyzed for anatomic (Response Evaluation Criteria in Solid Tumors [RECIST] and tumor volume) and functional (viable tumor volume, viable tumor burden, and apparent diffusion coefficient [ADC]) volumetric MR parameters by using semiautomatic software. Response was assessed by using changes in viable tumor volume by using modified RECIST (mRECIST)-derived thresholds (three-dimensional mRECIST), viable tumor burden, and ADC. Overall survival was the primary endpoint. Cox-regression and Kaplan-Meier survival analysis were used. Results Tumor volume did not change after TACE (P = .07) whereas RECIST diameter showed a small change (-2.6%; P = .02). There was an increase in ADC (20.7%) and a decrease in viable tumor volume (-29.3%) and viable tumor burden (-29.1%; P < .001 for all). Higher overall survival was noted among responders by using thresholds of 25% increase in ADC, 66% decrease in viable tumor volume, and 50% decrease in viable tumor burden (log-rank test, P < .05). Hazard ratio for nonresponders by using ADC, three-dimensional mRECIST, and viable tumor burden at multivariable analysis was 2.9 (P = .004), 4.1 (P = .009), and 4.0 (P = .002), respectively. Survival differences were noted for patients who showed response by using all three parameters (ADC, three-dimensional mRECIST, and viable tumor burden) versus those who showed response by using either one or two of these parameters versus those who showed no response (P < .001). Conclusion Changes in volumetric ADC, viable tumor volume, and viable tumor burden at MR imaging provide prognostic information among patients with unresectable ICCA who undergo TACE. (©) RSNA, 2018 Online supplemental material is available for this article.","Source":"PubMed","category":"HUMAN","training_data":"Unresectable Intrahepatic Cholangiocarcinoma: Multiparametric MR Imaging to Predict Patient Survival Purpose To determine the performance of magnetic resonance (MR) imaging-based tumor metrics for evaluation of response to transarterial chemoembolization (TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICCA). Materials and Methods Ninety-four patients with unresectable ICCA underwent baseline and follow-up MR imaging after TACE and were followed up until death or end of study duration. Lesions were analyzed for anatomic (Response Evaluation Criteria in Solid Tumors [RECIST] and tumor volume) and functional (viable tumor volume, viable tumor burden, and apparent diffusion coefficient [ADC]) volumetric MR parameters by using semiautomatic software. Response was assessed by using changes in viable tumor volume by using modified RECIST (mRECIST)-derived thresholds (three-dimensional mRECIST), viable tumor burden, and ADC. Overall survival was the primary endpoint. Cox-regression and Kaplan-Meier survival analysis were used. Results Tumor volume did not change after TACE (P = .07) whereas RECIST diameter showed a small change (-2.6%; P = .02). There was an increase in ADC (20.7%) and a decrease in viable tumor volume (-29.3%) and viable tumor burden (-29.1%; P < .001 for all). Higher overall survival was noted among responders by using thresholds of 25% increase in ADC, 66% decrease in viable tumor volume, and 50% decrease in viable tumor burden (log-rank test, P < .05). Hazard ratio for nonresponders by using ADC, three-dimensional mRECIST, and viable tumor burden at multivariable analysis was 2.9 (P = .004), 4.1 (P = .009), and 4.0 (P = .002), respectively. Survival differences were noted for patients who showed response by using all three parameters (ADC, three-dimensional mRECIST, and viable tumor burden) versus those who showed response by using either one or two of these parameters versus those who showed no response (P < .001). Conclusion Changes in volumetric ADC, viable tumor volume, and viable tumor burden at MR imaging provide prognostic information among patients with unresectable ICCA who undergo TACE. (©) RSNA, 2018 Online supplemental material is available for this article. PubMed","prediction_labels":"HUMAN"},{"cleaned":"parameters influencing survival resection intrahepatic cholangiocarcinoma ihcc background aim study identify prognostic impact metabolic parameters 18f fluorodeoxyglucose fdg positron emission tomography pet patients intrahepatic cholangiocarcinoma ihcc undergoing hepatic resection patients methods twenty four patients ihcc underwent surgical resection enrolled 18f fdg pet parameters maximum standardized uptake value suvmax metabolic tumor volume mtv total lesion glycolysis tlg measured well overall recurrence free survival results high tlg significantly associated large tumor size high carbohydrate antigen 19 9 level patients high suvmax high mtv high tlg significantly worse prognosis regarding overall recurrence free survival low suvmax low mtv low tlg respectively multivariate cox proportional hazards analysis identified high tlg significantly influenced overall recurrence free survival conclusion preoperative assessment tlg 18f fdg pet might useful prognostic predictor hepatic resection patients ihcc stn","probabilities":0.9799733,"Title":"Parameters Influencing Survival After Resection Of Intrahepatic Cholangiocarcinoma (Ihcc)","Abstract":"Background: The aim of this study was to identify the prognostic impact of metabolic parameters of 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) in patients with intrahepatic cholangiocarcinoma (IHCC) undergoing hepatic resection. \r\n\r\n Patients and methods: Twenty-four patients with IHCC who underwent surgical resection were enrolled and 18F-FDG PET parameters maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured, as well as overall and recurrence-free survival. \r\n\r\n Results: High TLG was significantly associated with large tumor size and high carbohydrate antigen 19-9 level. Patients with high SUVmax, high MTV or high TLG had a significantly worse prognosis regarding both overall and recurrence-free survival than those with low SUVmax, low MTV and low TLG, respectively. Multivariate Cox proportional hazards analysis identified that high TLG significantly influenced both overall and recurrence-free survival. \r\n\r\n Conclusion: Preoperative assessment of TLG by 18F-FDG PET might be a useful prognostic predictor after hepatic resection in patients with IHCC.","Source":"STN","category":"HUMAN","training_data":"Parameters Influencing Survival After Resection Of Intrahepatic Cholangiocarcinoma (Ihcc) Background: The aim of this study was to identify the prognostic impact of metabolic parameters of 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) in patients with intrahepatic cholangiocarcinoma (IHCC) undergoing hepatic resection. \r\n\r\n Patients and methods: Twenty-four patients with IHCC who underwent surgical resection were enrolled and 18F-FDG PET parameters maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured, as well as overall and recurrence-free survival. \r\n\r\n Results: High TLG was significantly associated with large tumor size and high carbohydrate antigen 19-9 level. Patients with high SUVmax, high MTV or high TLG had a significantly worse prognosis regarding both overall and recurrence-free survival than those with low SUVmax, low MTV and low TLG, respectively. Multivariate Cox proportional hazards analysis identified that high TLG significantly influenced both overall and recurrence-free survival. \r\n\r\n Conclusion: Preoperative assessment of TLG by 18F-FDG PET might be a useful prognostic predictor after hepatic resection in patients with IHCC. STN","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma current knowledge new developments cholangiocarcinoma cca second common primary malignancy although common asia incidence europe north america significantly increased recent decades prognosis cca dismal surgery potentially curative treatment majority patients present advanced stage disease recurrence resection common last two decades understanding molecular biology malignancy increased tremendously diagnostic techniques evolved novel therapeutic approaches established review discusses changing epidemiologic trends provides overview newly identified etiologic risk factors cca furthermore molecular pathogenesis discussed well influence etiology biliary location mutational landscape cca review provides overview diagnostic evaluation cca staging systems finally new therapeutic options critically reviewed future therapeutic strategies discussed pubmed","probabilities":0.9799733,"Title":"Cholangiocarcinoma: Current Knowledge and New Developments","Abstract":"Cholangiocarcinoma (CCA) is the second most common primary malignancy. Although it is more common in Asia, its incidence in Europe and North America has significantly increased in recent decades. The prognosis of CCA is dismal. Surgery is the only potentially curative treatment, but the majority of patients present with advanced stage disease, and recurrence after resection is common. Over the last two decades, our understanding of the molecular biology of this malignancy has increased tremendously, diagnostic techniques have evolved, and novel therapeutic approaches have been established. This review discusses the changing epidemiologic trends and provides an overview of newly identified etiologic risk factors for CCA. Furthermore, the molecular pathogenesis is discussed as well as the influence of etiology and biliary location on the mutational landscape of CCA. This review provides an overview of the diagnostic evaluation of CCA and its staging systems. Finally, new therapeutic options are critically reviewed, and future therapeutic strategies discussed.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma: Current Knowledge and New Developments Cholangiocarcinoma (CCA) is the second most common primary malignancy. Although it is more common in Asia, its incidence in Europe and North America has significantly increased in recent decades. The prognosis of CCA is dismal. Surgery is the only potentially curative treatment, but the majority of patients present with advanced stage disease, and recurrence after resection is common. Over the last two decades, our understanding of the molecular biology of this malignancy has increased tremendously, diagnostic techniques have evolved, and novel therapeutic approaches have been established. This review discusses the changing epidemiologic trends and provides an overview of newly identified etiologic risk factors for CCA. Furthermore, the molecular pathogenesis is discussed as well as the influence of etiology and biliary location on the mutational landscape of CCA. This review provides an overview of the diagnostic evaluation of CCA and its staging systems. Finally, new therapeutic options are critically reviewed, and future therapeutic strategies discussed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"diabetes mellitus possible risk promoting factors cholangiocarcinoma association diabetes mellitus cholangiocarcinoma highest incidence cholangiocarcinoma cca malignancy bile duct epithelia northeast thailand liver fluke opisthorchis viverrini known risk factor cca development region approximately 1 o viverrini infected individuals develop cca factors influence cholangiocarcinogenesis particularly o viverrini infected individuals global epidemiological studies risk factors cca non o viverrini related patients indicated diabetes mellitus dm risk factor cca molecular studies many cancers indicated high levels glucose insulin obese condition directly indirectly enhanced growth cancers o viverrini associated cca limited information related dm cca development high mortality rates cca dm however reported geographical areas northeastern thailand whether dm factor enhances cca development o viverrini infected individuals promotes cca progression discussed perspective epidemiological molecular studies pubmed","probabilities":0.9799733,"Title":"Diabetes mellitus: Possible risk and promoting factors of cholangiocarcinoma: Association of diabetes mellitus and cholangiocarcinoma","Abstract":"The highest incidence of Cholangiocarcinoma (CCA), a malignancy of bile duct epithelia, is in the Northeast of Thailand. The liver fluke, Opisthorchis viverrini, is the known risk factor for CCA development in this region. Approximately 1% of O. viverrini infected individuals develop CCA. There could be other factors that influence the cholangiocarcinogenesis particularly in the O. viverrini infected individuals. The global epidemiological studies of risk factors for CCA in non-O. viverrini related patients indicated diabetes mellitus (DM) as a risk factor of CCA. The molecular studies in many cancers indicated that high levels of glucose, insulin and an obese condition directly and indirectly enhanced growth of cancers. For O. viverrini associated CCA, there is limited information related to DM and CCA development. High mortality rates of CCA and DM, however, were reported in the same geographical areas of northeastern Thailand. Whether DM is a factor that enhances CCA development in O. viverrini infected individuals or promotes CCA progression are discussed in a perspective of epidemiological and molecular studies.","Source":"PubMed","category":"HUMAN","training_data":"Diabetes mellitus: Possible risk and promoting factors of cholangiocarcinoma: Association of diabetes mellitus and cholangiocarcinoma The highest incidence of Cholangiocarcinoma (CCA), a malignancy of bile duct epithelia, is in the Northeast of Thailand. The liver fluke, Opisthorchis viverrini, is the known risk factor for CCA development in this region. Approximately 1% of O. viverrini infected individuals develop CCA. There could be other factors that influence the cholangiocarcinogenesis particularly in the O. viverrini infected individuals. The global epidemiological studies of risk factors for CCA in non-O. viverrini related patients indicated diabetes mellitus (DM) as a risk factor of CCA. The molecular studies in many cancers indicated that high levels of glucose, insulin and an obese condition directly and indirectly enhanced growth of cancers. For O. viverrini associated CCA, there is limited information related to DM and CCA development. High mortality rates of CCA and DM, however, were reported in the same geographical areas of northeastern Thailand. Whether DM is a factor that enhances CCA development in O. viverrini infected individuals or promotes CCA progression are discussed in a perspective of epidemiological and molecular studies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"laparoscopic management incidental gallbladder cancer background laparoscopic cholecystectomy allowed detection increasing number incidental gallbladder cancers igbc although laparoscopy employed management variety abdominal tumors use gallbladder cancer reduced controversial study analyzes role laparoscopy gallbladder cancer focus igbc method evaluated prospective series 51 patients igbc treated laparoscopy 2006 2016 clinica alemana santiago google scholar","probabilities":0.9799733,"Title":"Laparoscopic Management Of Incidental Gallbladder Cancer","Abstract":"Background The laparoscopic cholecystectomy has allowed the detection of an increasing \nnumber of incidental gallbladder cancers (IGBC). Although laparoscopy is employed in the \nmanagement of a variety of abdominal tumors, its use in gallbladder cancer is reduced and \ncontroversial. This study analyzes the role of laparoscopy in gallbladder cancer with the \nfocus in IGBC. Method We evaluated our prospective series of 51 patients with an IGBC who \nwere treated by laparoscopy between 2006 and 2016 at the Clinica Alemana in Santiago","Source":"Google Scholar","category":"HUMAN","training_data":"Laparoscopic Management Of Incidental Gallbladder Cancer Background The laparoscopic cholecystectomy has allowed the detection of an increasing \nnumber of incidental gallbladder cancers (IGBC). Although laparoscopy is employed in the \nmanagement of a variety of abdominal tumors, its use in gallbladder cancer is reduced and \ncontroversial. This study analyzes the role of laparoscopy in gallbladder cancer with the \nfocus in IGBC. Method We evaluated our prospective series of 51 patients with an IGBC who \nwere treated by laparoscopy between 2006 and 2016 at the Clinica Alemana in Santiago Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"tumor protein p53 k ras gene mutations peruvian patients gallbladder cancer background recent studies shown genetic alterations associated effect patient geographic location gallbladder cancer development peru high incidence gallbladder cancer causative factors yet identified examined frequency mutations tp53 k ras genes peruvian patients gallbladder cancer compared data bolivia hungary chile japan high gallbladder cancer incidence methods dna extracted formalin fixed paraffin embedded gallbladder tissue sections 30 gallbladder cancer patients 9 men 21 women obtained using microdissection mutations exons 5 8 tp53 codons 12 13 61 k ras examined using direct sequencing results tp53 mutations observed 10 33 3 patients k ras mutations absent nine 90 tp53 mutations point mutations 7 missense 2 silent mutations frequent substitution g c transition g c transitions cpg site g c transversions found one patient significant differences found frequency tp53 k ras mutations among patients 5 countries conclusions findings suggest endogenous mechanisms exogenous carcinogens may affect carcinogenic process peruvian gallbladder cancer patients similar bolivian patients studies larger sample size needed clarify findings stn","probabilities":0.875,"Title":"Tumor Protein P53 And K-Ras Gene Mutations In Peruvian Patients With Gallbladder Cancer","Abstract":"Background: Recent studies have shown that genetic alterations are associated with the effect of patient geographic location on gallbladder cancer development. Peru has a high incidence of gallbladder cancer, but causative factors have not yet been identified. We examined the frequency of mutations in TP53 and K-ras genes in Peruvian patients with gallbladder cancer, and compared this with data from Bolivia, Hungary, Chile, and Japan, which have a high gallbladder cancer incidence. Methods: DNA was extracted from formalin-fixed paraffin-embedded gallbladder tissue sections of 30 gallbladder cancer patients (9 men and 21 women) obtained using microdissection. Mutations in exons 5 to 8 of TP53 and codons 12, 13, and 61 of K-ras were examined using direct sequencing. Results: TP53 mutations were observed in 10 (33.3%) of patients, but K-ras mutations were absent. Nine (90%) TP53 mutations were point mutations (7 missense and 2 silent mutations), and the most frequent substitution was a G:C to A:T transition. G:C to A:T transitions at the CpG site or G:C to T:A transversions were found in one patient each. No significant differences were found in the frequency of TP53 and K-ras mutations among patients in the 5 countries. Conclusions: Our findings suggest that endogenous mechanisms and exogenous carcinogens may affect the carcinogenic process in Peruvian gallbladder cancer patients, similar to that in Bolivian patients. Further studies with a larger sample size are needed to clarify these findings.","Source":"STN","category":"ANIMAL","training_data":"Tumor Protein P53 And K-Ras Gene Mutations In Peruvian Patients With Gallbladder Cancer Background: Recent studies have shown that genetic alterations are associated with the effect of patient geographic location on gallbladder cancer development. Peru has a high incidence of gallbladder cancer, but causative factors have not yet been identified. We examined the frequency of mutations in TP53 and K-ras genes in Peruvian patients with gallbladder cancer, and compared this with data from Bolivia, Hungary, Chile, and Japan, which have a high gallbladder cancer incidence. Methods: DNA was extracted from formalin-fixed paraffin-embedded gallbladder tissue sections of 30 gallbladder cancer patients (9 men and 21 women) obtained using microdissection. Mutations in exons 5 to 8 of TP53 and codons 12, 13, and 61 of K-ras were examined using direct sequencing. Results: TP53 mutations were observed in 10 (33.3%) of patients, but K-ras mutations were absent. Nine (90%) TP53 mutations were point mutations (7 missense and 2 silent mutations), and the most frequent substitution was a G:C to A:T transition. G:C to A:T transitions at the CpG site or G:C to T:A transversions were found in one patient each. No significant differences were found in the frequency of TP53 and K-ras mutations among patients in the 5 countries. Conclusions: Our findings suggest that endogenous mechanisms and exogenous carcinogens may affect the carcinogenic process in Peruvian gallbladder cancer patients, similar to that in Bolivian patients. Further studies with a larger sample size are needed to clarify these findings. STN","prediction_labels":"ANIMAL"},{"cleaned":"natural history metastatic biliary tract cancer btc patients good performance status ps treated best supportive care bsc background although chemotherapy widely recommended patients metastatic biliary tract cancer natural course patients especially good performance status indicated chemotherapy known methods retrospectively reviewed patients metastatic locally advanced biliary cancer diagnosed six cancer centers patients eligible good performance ecog 0 2 history treatment cancer primary objective evaluate survival time patients advanced biliary cancer good performance untreated results 1677 patients 204 met inclusion criteria median age overall survival 72 0 years 7 1 months overall survival months location 4 7 intrahepatic 9 7 extrahepatic 4 4 gallbladder 11 2 ampulla vater cancer subgroup analysis overall survival locally advanced biliary cancer 13 8 months patients normal carcinoembryonic antigen carbohydrate antigen 19 9 10 6 months multivariate analysis variables associated poor prognosis metastatic biliary cancer hazard ratio 2 19 p 0 001 high baseline carcinoembryonic antigen level defined 4 0 ng ml hazard ratio 1 51 p 0 024 high baseline carbohydrate antigen 19 9 level defined 100 u ml hazard ratio 1 93 p 0 001 conclusions advanced biliary tract cancer good performance status showed modest survival without treatment furthermore subgroup analysis showed patients normal carbohydrate antigen 19 9 carcinoembryonic antigen level locally advanced status favorable survival studies comparing outcome chemotherapy best supportive care patients unresectable biliary tract cancer warranted pubmed","probabilities":0.9799733,"Title":"Natural history of metastatic biliary tract cancer (BTC) patients with good performance status (PS) who were treated with only best supportive care (BSC)","Abstract":"BACKGROUND: Although chemotherapy is widely recommended for patients with metastatic biliary tract cancer, the natural course of these patients, especially those with good performance status who are indicated for chemotherapy, is not known. METHODS: We retrospectively reviewed patients with metastatic or locally advanced biliary cancer who were diagnosed at six cancer centers. Patients were eligible if they had good performance (ECOG 0-2) and no history of any treatment for cancer. The primary objective was to evaluate the survival time of patients with advanced biliary cancer with good performance who were untreated. RESULTS: Of the 1677 patients, 204 met the inclusion criteria. The median age and overall survival were 72.0 years and 7.1 months. Overall survival (months) by location was 4.7 for intrahepatic, 9.7 for extrahepatic, 4.4 for gallbladder and 11.2 for ampulla of vater cancer. In subgroup analysis, overall survival of locally advanced biliary cancer was 13.8 months and that of patients with normal carcinoembryonic antigen/carbohydrate antigen 19-9 was 10.6 months. In multivariate analysis, variables that were associated with poor prognosis were metastatic biliary cancer [hazard ratio 2.19 (P = 0.001)], high baseline carcinoembryonic antigen level (defined as >4.0 ng/ml) [hazard ratio 1.51 (P = 0.024)] and high baseline carbohydrate antigen 19-9 level (defined as >100 U/ml) [hazard ratio 1.93 (P = 0.001)]. CONCLUSIONS: Advanced biliary tract cancer with good performance status showed modest survival without any treatment. Furthermore, subgroup analysis showed that patients with normal carbohydrate antigen 19-9 or carcinoembryonic antigen level or locally advanced status had favorable survival. Further studies comparing the outcome of chemotherapy with that of best supportive care in patients with unresectable biliary tract cancer are warranted.","Source":"PubMed","category":"HUMAN","training_data":"Natural history of metastatic biliary tract cancer (BTC) patients with good performance status (PS) who were treated with only best supportive care (BSC) BACKGROUND: Although chemotherapy is widely recommended for patients with metastatic biliary tract cancer, the natural course of these patients, especially those with good performance status who are indicated for chemotherapy, is not known. METHODS: We retrospectively reviewed patients with metastatic or locally advanced biliary cancer who were diagnosed at six cancer centers. Patients were eligible if they had good performance (ECOG 0-2) and no history of any treatment for cancer. The primary objective was to evaluate the survival time of patients with advanced biliary cancer with good performance who were untreated. RESULTS: Of the 1677 patients, 204 met the inclusion criteria. The median age and overall survival were 72.0 years and 7.1 months. Overall survival (months) by location was 4.7 for intrahepatic, 9.7 for extrahepatic, 4.4 for gallbladder and 11.2 for ampulla of vater cancer. In subgroup analysis, overall survival of locally advanced biliary cancer was 13.8 months and that of patients with normal carcinoembryonic antigen/carbohydrate antigen 19-9 was 10.6 months. In multivariate analysis, variables that were associated with poor prognosis were metastatic biliary cancer [hazard ratio 2.19 (P = 0.001)], high baseline carcinoembryonic antigen level (defined as >4.0 ng/ml) [hazard ratio 1.51 (P = 0.024)] and high baseline carbohydrate antigen 19-9 level (defined as >100 U/ml) [hazard ratio 1.93 (P = 0.001)]. CONCLUSIONS: Advanced biliary tract cancer with good performance status showed modest survival without any treatment. Furthermore, subgroup analysis showed that patients with normal carbohydrate antigen 19-9 or carcinoembryonic antigen level or locally advanced status had favorable survival. Further studies comparing the outcome of chemotherapy with that of best supportive care in patients with unresectable biliary tract cancer are warranted. PubMed","prediction_labels":"HUMAN"},{"cleaned":"molecular pathways targeted therapy cholangiocarcinoma cholangiocarcinoma cca encompasses rare group malignancies arising epithelial cells lining biliary tree connects liver gallbladder small intestine patients present advanced incurable disease poor prognosis standard treatment options remain limited effective nontoxic treatment options advanced cca needed fibroblast growth factors fgfs fibroblast growth factor receptor fgfr pathways crucial cellular proliferation cellular survival differentiation many malignancies especially relevant cca targeting fgf fgfr become promising approach treating patients advanced metastatic cca review cca discuss promise fgfr directed therapy advanced cca pubmed","probabilities":0.9799733,"Title":"Molecular pathways and targeted therapy in cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) encompasses a rare group of malignancies arising from epithelial cells lining the biliary tree that connects the liver and gallbladder to the small intestine. Most patients present with advanced incurable disease that has a poor prognosis, and standard treatment options remain limited. Effective nontoxic treatment options for advanced CCA are needed. Fibroblast growth factors (FGFs) and their fibroblast growth factor receptor (FGFR) pathways are crucial to cellular proliferation, cellular survival, and differentiation of many malignancies, but are especially relevant in CCA. The targeting of FGF/FGFR has become the most promising approach to treating patients with advanced/metastatic CCA. Here we review CCA, and discuss the promise of FGFR-directed therapy in advanced CCA.","Source":"PubMed","category":"HUMAN","training_data":"Molecular pathways and targeted therapy in cholangiocarcinoma Cholangiocarcinoma (CCA) encompasses a rare group of malignancies arising from epithelial cells lining the biliary tree that connects the liver and gallbladder to the small intestine. Most patients present with advanced incurable disease that has a poor prognosis, and standard treatment options remain limited. Effective nontoxic treatment options for advanced CCA are needed. Fibroblast growth factors (FGFs) and their fibroblast growth factor receptor (FGFR) pathways are crucial to cellular proliferation, cellular survival, and differentiation of many malignancies, but are especially relevant in CCA. The targeting of FGF/FGFR has become the most promising approach to treating patients with advanced/metastatic CCA. Here we review CCA, and discuss the promise of FGFR-directed therapy in advanced CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role quantitative tfpi2 methylation novel serum diagnostic prognostic marker hepatopancreaticobiliary cancers introduction hepatopancreaticobiliary cancers include liver gall bladder bile duct pancreas cancer high prevalence important ranks cancer related deaths 1 biomarker studies serum circulating cell free dna cfdna popular subject epigenetic changes different forms cfdna changes crucial role tumorigenesis steps changes methylation gene promoter sequences epigenetic silencing tumor suppressor genes important role hepatobiliary cancers 2 studies shown detection methylated serum cfdna recommended early diagnosis method hepatopancreaticobiliary cancers 3 5 study aim study tissue factor pathway inhibitor 2 tfpi2 gene methylation profile serum hepatopancreaticobiliary cancer patients using gene non invasive biomarker diagnosis prognosis cancers methods 69 patients hepatopancreaticobiliary cancer 28 healthy individuals upper gastrointestinal complaints without cancer included study serum samples collected patient groups control group stored 80 c distant metastases patients recorded patients monitored survival cfdna extracted serum sample extracted cfdna treated bisulfide methylation sensitive high resolution melting ms hrm analysis performed evaluate tfpi2 methylation status bisulfide sequencing analysis also performed determine methylated regions results three patients excluded statistical analysis due failure dna extraction found significant correlation methylation profile diagnosis hepatopancreaticobiliary cancers p 0 001 table 1 univariate analysis indicated methylation profile tfpi 2 presence comorbidities significant effects prognosis table 2 multivariate analysis table 3 showed methylated tfpi 2 independent prognostic biomarker poor os hazard ratio hr 3 044 95 ci 1 4 6 5 p 0 004 conclusion conclusion study demonstrated serum tfpi2 methylation used potential marker non invasive detection hepatopancreaticobiliary cancers also demonstrated survival serum tfpi2 methylation significantly correlated studies larger populations needed google scholar","probabilities":1.0,"Title":"The Role Of Quantitative Tfpi2 Methylation As A Novel Serum Diagnostic And Prognostic Marker In Hepatopancreaticobiliary Cancers","Abstract":"Introduction: Hepatopancreaticobiliary cancers which include liver, gall bladder, bile duct and pancreas cancer, have high prevalence and important ranks in cancer related deaths (1). Between biomarker studies, serum circulating cell-free DNA (cfDNA) is a popular subject. Epigenetic changes, different than other forms of cfDNA changes, have a crucial role in tumorigenesis and further steps. Because of the changes in the methylation of gene promoter sequences, epigenetic silencing of tumor suppressor genes has an important role in hepatobiliary cancers (2). Studies have shown that, detection of methylated serum cfDNA is the most recommended early diagnosis method of hepatopancreaticobiliary cancers (3-5). In our study, we aim to study the Tissue factor pathway inhibitor-2 (TFPI2) gene methylation profile in the serum of hepatopancreaticobiliary cancer patients and using this gene as a non-invasive biomarker in diagnosis and prognosis of these cancers.\nMethods: 69 patients with hepatopancreaticobiliary cancer and 28 healthy individuals with upper gastrointestinal complaints and without cancer were included in this study. Serum samples were collected from patient groups and control group and stored in -80 °C. Distant metastases of patients were recorded and patients were monitored for survival. cfDNA was extracted from each serum sample and extracted cfDNA was treated with bisulfide. Methylation Sensitive High Resolution Melting (MS-HRM) analysis was performed to evaluate the TFPI2 methylation status. Bisulfide sequencing analysis was also performed to determine the methylated regions.\nResults: Three patients were excluded from statistical analysis due to failure in DNA extraction. We found significant correlation between methylation profile and diagnosis of hepatopancreaticobiliary cancers (p < 0,001) (Table 1). Univariate analysis indicated that methylation profile of TFPI-2, presence of comorbidities had significant effects on prognosis (Table 2). Multivariate analysis (Table 3) further showed that methylated TFPI-2 was an independent prognostic biomarker for poor OS [hazard ratio (HR) = 3,044; 95% CI 1,4-6,5; P = 0.004].\nConclusion: In conclusion, our study demonstrated that serum TFPI2 methylation could be used as a potential marker for non-invasive detection of hepatopancreaticobiliary cancers. It is also demonstrated that survival and serum TFPI2 methylation can be significantly correlated. Further studies with larger populations are needed.","Source":"Google Scholar","category":"HUMAN","training_data":"The Role Of Quantitative Tfpi2 Methylation As A Novel Serum Diagnostic And Prognostic Marker In Hepatopancreaticobiliary Cancers Introduction: Hepatopancreaticobiliary cancers which include liver, gall bladder, bile duct and pancreas cancer, have high prevalence and important ranks in cancer related deaths (1). Between biomarker studies, serum circulating cell-free DNA (cfDNA) is a popular subject. Epigenetic changes, different than other forms of cfDNA changes, have a crucial role in tumorigenesis and further steps. Because of the changes in the methylation of gene promoter sequences, epigenetic silencing of tumor suppressor genes has an important role in hepatobiliary cancers (2). Studies have shown that, detection of methylated serum cfDNA is the most recommended early diagnosis method of hepatopancreaticobiliary cancers (3-5). In our study, we aim to study the Tissue factor pathway inhibitor-2 (TFPI2) gene methylation profile in the serum of hepatopancreaticobiliary cancer patients and using this gene as a non-invasive biomarker in diagnosis and prognosis of these cancers.\nMethods: 69 patients with hepatopancreaticobiliary cancer and 28 healthy individuals with upper gastrointestinal complaints and without cancer were included in this study. Serum samples were collected from patient groups and control group and stored in -80 °C. Distant metastases of patients were recorded and patients were monitored for survival. cfDNA was extracted from each serum sample and extracted cfDNA was treated with bisulfide. Methylation Sensitive High Resolution Melting (MS-HRM) analysis was performed to evaluate the TFPI2 methylation status. Bisulfide sequencing analysis was also performed to determine the methylated regions.\nResults: Three patients were excluded from statistical analysis due to failure in DNA extraction. We found significant correlation between methylation profile and diagnosis of hepatopancreaticobiliary cancers (p < 0,001) (Table 1). Univariate analysis indicated that methylation profile of TFPI-2, presence of comorbidities had significant effects on prognosis (Table 2). Multivariate analysis (Table 3) further showed that methylated TFPI-2 was an independent prognostic biomarker for poor OS [hazard ratio (HR) = 3,044; 95% CI 1,4-6,5; P = 0.004].\nConclusion: In conclusion, our study demonstrated that serum TFPI2 methylation could be used as a potential marker for non-invasive detection of hepatopancreaticobiliary cancers. It is also demonstrated that survival and serum TFPI2 methylation can be significantly correlated. Further studies with larger populations are needed. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic importance number metastatic lymph nodes patients undergoing curative resection followed adjuvant chemoradiotherapy extrahepatic bile duct cancer background current nodal staging system extrahepatic bile duct ehbd cancer controversial number metastatic lymph nodes mln lymph node ratio lnr studied assessment nodal status many gastrointestinal cancers studies assessing prognostic impact parameters ehbd cancer methods retrospectively reviewed 239 consecutive patients underwent curative resection followed adjuvant chemoradiotherapy adenocarcinoma ehbd 1995 2009 institution prognostic value number mln lnr evaluated adjusting known factors optimal cutoff points determined using maximally selected chi square test results lymph node metastasis found 77 32 patients univariate analysis overall survival os revealed number mln 0 vs 1 3 vs 4 p 0 001 lnr 0 2 vs 0 2 p 0 001 significant prognosticators multivariate analysis demonstrated number mln independent prognostic factor whereas lnr estimated 5 year os 48 7 patients negative nodes 33 4 patients 1 3 mln 9 1 patients 4 mln p 0 001 conclusions number mln powerful parameter predict survival ehbd cancer reliable lnr many gastrointestinal cancers classification node positive patients based number mln seems useful may provide precise information pubmed","probabilities":0.9799733,"Title":"The Prognostic Importance of the Number of Metastatic Lymph Nodes for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiotherapy for Extrahepatic Bile Duct Cancer","Abstract":"BACKGROUND: Current nodal staging system for extrahepatic bile duct (EHBD) cancer is controversial. The number of metastatic lymph nodes (mLN) and lymph node ratio (LNR) has been studied for the assessment of the nodal status in many other gastrointestinal cancers, but there are few studies on assessing the prognostic impact of these parameters in EHBD cancer. METHODS: We retrospectively reviewed 239 consecutive patients who underwent curative resection followed by adjuvant chemoradiotherapy for adenocarcinoma of EHBD from 1995 to 2009 in our institution. The prognostic value of the number of mLN and LNR was evaluated by adjusting for other known factors. Optimal cutoff points were determined using maximally selected chi-square test. RESULTS: Lymph node metastasis was found in 77 (32 %) patients. Univariate analysis for overall survival (OS) revealed both the number of mLN (0 vs. 1-3 vs. ≥4; p < 0.001) and LNR (<0.2 vs. ≥0.2; p < 0.001) as significant prognosticators. Multivariate analysis demonstrated that the number of mLN was an independent prognostic factor, whereas LNR was not. The estimated 5-year OS was 48.7 % for patients with negative nodes, 33.4 % for patients with 1-3 mLN, and 9.1 % for patients with 4 or more mLN (p < 0.001). CONCLUSIONS: The number of mLN is a powerful parameter to predict survival in the EHBD cancer, which is more reliable than LNR. As for many other gastrointestinal cancers, further classification of node positive patients based on the number of mLN seems to be useful and may provide precise information.","Source":"PubMed","category":"HUMAN","training_data":"The Prognostic Importance of the Number of Metastatic Lymph Nodes for Patients Undergoing Curative Resection Followed by Adjuvant Chemoradiotherapy for Extrahepatic Bile Duct Cancer BACKGROUND: Current nodal staging system for extrahepatic bile duct (EHBD) cancer is controversial. The number of metastatic lymph nodes (mLN) and lymph node ratio (LNR) has been studied for the assessment of the nodal status in many other gastrointestinal cancers, but there are few studies on assessing the prognostic impact of these parameters in EHBD cancer. METHODS: We retrospectively reviewed 239 consecutive patients who underwent curative resection followed by adjuvant chemoradiotherapy for adenocarcinoma of EHBD from 1995 to 2009 in our institution. The prognostic value of the number of mLN and LNR was evaluated by adjusting for other known factors. Optimal cutoff points were determined using maximally selected chi-square test. RESULTS: Lymph node metastasis was found in 77 (32 %) patients. Univariate analysis for overall survival (OS) revealed both the number of mLN (0 vs. 1-3 vs. ≥4; p < 0.001) and LNR (<0.2 vs. ≥0.2; p < 0.001) as significant prognosticators. Multivariate analysis demonstrated that the number of mLN was an independent prognostic factor, whereas LNR was not. The estimated 5-year OS was 48.7 % for patients with negative nodes, 33.4 % for patients with 1-3 mLN, and 9.1 % for patients with 4 or more mLN (p < 0.001). CONCLUSIONS: The number of mLN is a powerful parameter to predict survival in the EHBD cancer, which is more reliable than LNR. As for many other gastrointestinal cancers, further classification of node positive patients based on the number of mLN seems to be useful and may provide precise information. PubMed","prediction_labels":"HUMAN"},{"cleaned":"yttrium 90 radioembolization unresectable standard chemorefractory intrahepatic cholangiocarcinoma survival efficacy safety study purpose assess overall survival efficacy safety radioembolization yttrium 90 y90 unresectable standard chemorefractory intrahepatic cholangiocarcinoma icc methods patients unresectable standard chemorefractory icc treated y90 studied survival calculated date first y90 procedure tumor response assessed response evaluation criteria solid tumors criteria follow computed tomography magnetic resonance imaging scans national cancer institute common terminology criteria nci ctcae version 3 used complications statistical analysis performed kaplan meier estimator log rank test results nineteen patients underwent total 24 resin based y90 treatments median survival time diagnosis first y90 procedure 752 193 95 confidence interval ci 374 1130 345 128 95 ci 95 595 days respectively median survival eastern cooperative oncology group ecog performance status 1 n 15 ecog performance status 2 n 4 450 190 95 ci 78 822 345 227 95 ci 0 790 days respectively p 214 patients extrahepatic metastasis n 11 median survival 404 309 95 ci 0 1010 days versus 345 117 95 ci 115 575 days patients without metastasis n 8 p 491 mortality reported within 30 days first y90 radioembolization one patient developed grade 3 thrombocytopenia assessed nci ctcae fatigue transient abdominal pain observed 4 21 6 32 patients respectively conclusion y90 radioembolization effective unresectable standard chemorefractory icc stn","probabilities":0.9799733,"Title":"Yttrium-90 Radioembolization For Unresectable Standard-Chemorefractory Intrahepatic Cholangiocarcinoma: Survival Efficacy And Safety Study","Abstract":"Purpose: To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan-Meier estimator by the log rank test. \r\n\r\n Results: Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 ± 193 [95 % confidence interval (CI) 374-1130] and 345 ± 128 (95 % CI 95-595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 ± 190 (95 % CI 78-822) and 345 ± 227 (95 % CI 0-790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 ± 309 (95 % CI 0-1010) days versus 345 ± 117 (95 % CI 115-575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively. \r\n\r\n Conclusion: Y90 radioembolization is effective for unresectable standard-chemorefractory ICC.","Source":"STN","category":"HUMAN","training_data":"Yttrium-90 Radioembolization For Unresectable Standard-Chemorefractory Intrahepatic Cholangiocarcinoma: Survival Efficacy And Safety Study Purpose: To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan-Meier estimator by the log rank test. \r\n\r\n Results: Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 ± 193 [95 % confidence interval (CI) 374-1130] and 345 ± 128 (95 % CI 95-595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 ± 190 (95 % CI 78-822) and 345 ± 227 (95 % CI 0-790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 ± 309 (95 % CI 0-1010) days versus 345 ± 117 (95 % CI 115-575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively. \r\n\r\n Conclusion: Y90 radioembolization is effective for unresectable standard-chemorefractory ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"new clinically based staging system distal cholangiocarcinoma background clinical predictors survival subtype cholangiocarcinoma intrahepatic perihilar distal dcca limited currently available staging systems used predict prognosis resectable dcca relevant patients unresectable disease based limitations aimed construct clinical staging system stratifies dcca patients methods identified 170 treatment na ve dcca patients seen mayo clinic rochester january 1 2000 may 31 2014 data retrospectively abstracted electronic medical record overall median survival ms primary endpoint estimated using kaplan meier method compared using log rank test cox proportional hazards analysis used identify predictors survival performance staging system assessed using concordance index results 170 dcca patients 93 58 male mean age 67 years 19 12 primary sclerosing cholangitis ms entire cohort 17 0 months 95 confidence interval ci 14 0 20 5 baseline ecog performance status post stenting ca 19 9 disease extent significantly associated survival incorporated 4 tier staging system total 143 patients classified new staging system overall ms patients stage stage ii stage iii stage iv 46 8 14 3 8 1 3 4 months hazard ratios 95 ci 1 0 ref 1 9 1 0 3 4 4 1 2 3 7 0 9 7 5 1 18 5 respectively concordance index new staging system 0 73 conclusion developed new staging system based non operative clinical variables classifies dcca patients 4 distinct stages homogeneous survival given small cohort validation confirm findings crucial however staging system potentially key prognostic tool better stratification patients enrolled clinical trials novel therapies dcca google scholar","probabilities":0.9799733,"Title":"A New Clinically-Based Staging System For Distal Cholangiocarcinoma","Abstract":"Background: Clinical predictors of survival for each subtype of cholangiocarcinoma, intrahepatic, perihilar and distal (dCCA) are limited. Currently available staging systems can be used to predict prognosis for resectable dCCA but are not relevant to patients with unresectable disease. Based on these limitations, we aimed to construct a clinical staging system that stratifies dCCA patients. \nMethods: We identified 170 treatment-naïve dCCA patients seen at Mayo Clinic, Rochester from January 1, 2000 through May 31, 2014. Data were retrospectively abstracted from the electronic medical record. Overall median survival (MS), the primary endpoint, was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox-proportional hazards analysis was used to identify predictors of survival. Performance of the staging system was assessed using concordance index. \nResults: Of the 170 dCCA patients, 93 (58%) were male, the mean age was 67 years, and 19 (12%) had primary sclerosing cholangitis. The MS of the entire cohort was 17.0 months (95% confidence interval [CI]: 14.0-20.5). Baseline ECOG performance status, post-stenting CA 19-9 and disease extent were significantly associated with survival and further incorporated into a 4-tier staging system. A total of 143 patients were classified into the new staging system. Overall MS for patients in Stage I, Stage II, Stage III and Stage IV were 46.8, 14.3, 8.1, and 3.4 months, with hazard ratios (95% CI) of 1.0 (ref.), 1.9 (1.0-3.4), 4.1 (2.3-7.0), and 9.7 (5.1-18.5), respectively. Concordance index for the new staging system was 0.73. \n\nConclusion: We have developed a new staging system based on non-operative clinical variables that classifies dCCA patients into 4 distinct stages with homogeneous survival. Given the small cohort, validation to confirm these findings is crucial. However, this staging system could potentially be a key prognostic tool for better stratification of patients enrolled in clinical trials of novel therapies for dCCA","Source":"Google Scholar","category":"HUMAN","training_data":"A New Clinically-Based Staging System For Distal Cholangiocarcinoma Background: Clinical predictors of survival for each subtype of cholangiocarcinoma, intrahepatic, perihilar and distal (dCCA) are limited. Currently available staging systems can be used to predict prognosis for resectable dCCA but are not relevant to patients with unresectable disease. Based on these limitations, we aimed to construct a clinical staging system that stratifies dCCA patients. \nMethods: We identified 170 treatment-naïve dCCA patients seen at Mayo Clinic, Rochester from January 1, 2000 through May 31, 2014. Data were retrospectively abstracted from the electronic medical record. Overall median survival (MS), the primary endpoint, was estimated using the Kaplan-Meier method and compared using the log-rank test. Cox-proportional hazards analysis was used to identify predictors of survival. Performance of the staging system was assessed using concordance index. \nResults: Of the 170 dCCA patients, 93 (58%) were male, the mean age was 67 years, and 19 (12%) had primary sclerosing cholangitis. The MS of the entire cohort was 17.0 months (95% confidence interval [CI]: 14.0-20.5). Baseline ECOG performance status, post-stenting CA 19-9 and disease extent were significantly associated with survival and further incorporated into a 4-tier staging system. A total of 143 patients were classified into the new staging system. Overall MS for patients in Stage I, Stage II, Stage III and Stage IV were 46.8, 14.3, 8.1, and 3.4 months, with hazard ratios (95% CI) of 1.0 (ref.), 1.9 (1.0-3.4), 4.1 (2.3-7.0), and 9.7 (5.1-18.5), respectively. Concordance index for the new staging system was 0.73. \n\nConclusion: We have developed a new staging system based on non-operative clinical variables that classifies dCCA patients into 4 distinct stages with homogeneous survival. Given the small cohort, validation to confirm these findings is crucial. However, this staging system could potentially be a key prognostic tool for better stratification of patients enrolled in clinical trials of novel therapies for dCCA Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"detection hepatitis b virus dna paraffin embedded intrahepatic extrahepatic cholangiocarcinoma tissue northern chinese population study explored importance hepatitis b virus infection cholangiocarcinoma pathogenesis northern china clinical data 66 patients cholangiocarcinoma analyzed hepatitis b virus gene amplified using nested polymerase chain reaction hepatitis b virus related antigen detected using immunohistochemistry formalin fixed paraffin embedded tissue patients intrahepatic cholangiocarcinoma n 23 extrahepatic cholangiocarcinoma n 43 hepatitis b surface antigen seropositivity found 52 2 12 23 intrahepatic cholangiocarcinoma cases 13 9 6 43 extrahepatic cholangiocarcinoma cases hepatitis b virus dna x region detectable 34 8 8 23 intrahepatic cholangiocarcinoma cases hepatitis b surface antigen hepatitis b core antigen detectable 30 4 7 23 intrahepatic cholangiocarcinoma cases cases detected viral protein also positive hepatitis b virus dna contrast hepatitis b virus antigens hepatitis b virus gene detected 43 extrahepatic cholangiocarcinoma cases findings strongly suggest chronic hepatitis b virus infection significant risk factor intrahepatic cholangiocarcinoma extrahepatic cholangiocarcinoma northern china hepatitis b virus infection potentially independently associated intrahepatic cholangiocarcinoma stn","probabilities":0.875,"Title":"Detection Of Hepatitis B Virus Dna In Paraffin-Embedded Intrahepatic And Extrahepatic Cholangiocarcinoma Tissue In The Northern Chinese Population","Abstract":"This study explored the importance of hepatitis B virus infection in cholangiocarcinoma pathogenesis in northern China. The clinical data of 66 patients with cholangiocarcinoma were analyzed. The hepatitis B virus gene was amplified using nested polymerase chain reaction, and the hepatitis B virus-related antigen was detected using immunohistochemistry in formalin-fixed, paraffin-embedded tissue from patients with intrahepatic cholangiocarcinoma (n = 23) and extrahepatic cholangiocarcinoma (n = 43). Hepatitis B surface antigen seropositivity was found in 52.2% (12/23) of intrahepatic cholangiocarcinoma cases and 13.9% (6/43) of extrahepatic cholangiocarcinoma cases. Hepatitis B virus DNA (X region) was detectable in 34.8% (8/23) of intrahepatic cholangiocarcinoma cases. Hepatitis B surface antigen and/or hepatitis B core antigen was detectable in 30.4% (7/23) of intrahepatic cholangiocarcinoma cases. All cases with detected viral protein were also positive for hepatitis B virus DNA. In contrast, no hepatitis B virus antigens or hepatitis B virus gene was detected in any of the 43 extrahepatic cholangiocarcinoma cases. Our findings strongly suggest that chronic hepatitis B virus infection is a significant risk factor for intrahepatic cholangiocarcinoma, but not for extrahepatic cholangiocarcinoma, in northern China. Hepatitis B virus infection is potentially independently associated with intrahepatic cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Detection Of Hepatitis B Virus Dna In Paraffin-Embedded Intrahepatic And Extrahepatic Cholangiocarcinoma Tissue In The Northern Chinese Population This study explored the importance of hepatitis B virus infection in cholangiocarcinoma pathogenesis in northern China. The clinical data of 66 patients with cholangiocarcinoma were analyzed. The hepatitis B virus gene was amplified using nested polymerase chain reaction, and the hepatitis B virus-related antigen was detected using immunohistochemistry in formalin-fixed, paraffin-embedded tissue from patients with intrahepatic cholangiocarcinoma (n = 23) and extrahepatic cholangiocarcinoma (n = 43). Hepatitis B surface antigen seropositivity was found in 52.2% (12/23) of intrahepatic cholangiocarcinoma cases and 13.9% (6/43) of extrahepatic cholangiocarcinoma cases. Hepatitis B virus DNA (X region) was detectable in 34.8% (8/23) of intrahepatic cholangiocarcinoma cases. Hepatitis B surface antigen and/or hepatitis B core antigen was detectable in 30.4% (7/23) of intrahepatic cholangiocarcinoma cases. All cases with detected viral protein were also positive for hepatitis B virus DNA. In contrast, no hepatitis B virus antigens or hepatitis B virus gene was detected in any of the 43 extrahepatic cholangiocarcinoma cases. Our findings strongly suggest that chronic hepatitis B virus infection is a significant risk factor for intrahepatic cholangiocarcinoma, but not for extrahepatic cholangiocarcinoma, in northern China. Hepatitis B virus infection is potentially independently associated with intrahepatic cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"ck7 ck19 index potential prognostic factor postoperative intrahepatic cholangiocarcinoma patients background objectives frequently aberrant expression cytokeratin 7 ck7 cytokeratin 19 ck19 observed several human cancers retrospective study aimed investigating prognostic significance ck7 ck19 intrahepatic cholangiocarcinoma icc methods immunohistochemistry performed assess ck7 ck19 expression tissue microarrays training cohort enrolling 214 icc patients validation cohort comprising 108 icc patients kaplan meier analysis cox proportional hazards regression nomogram applied evaluate prognostic significance cks results ck7 ck19 expression significantly regulated icc compared non tumor counterparts positively correlated aggressive tumor phenotypes like lymph node metastasis larger tumor size furthermore high expression either ck7 ck19 predicted significantly dismal postoperative survival integrated analysis ck7 ck19 expression identified better indicator survival probability notably nomogram integrating ck7 ck19 index perfect prognostic performance compared current staging systems results confirmed validation cohort conclusions ck7 ck19 index independent adverse prognostic factor icc patients survival may helpful improve postoperative risk stratification individualized treatment strategies pubmed","probabilities":0.8684211,"Title":"CK7/CK19 index: A potential prognostic factor for postoperative intrahepatic cholangiocarcinoma patients","Abstract":"BACKGROUND AND OBJECTIVES: Frequently aberrant expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) have been observed in several human cancers. In this retrospective study, we aimed at investigating the prognostic significance of CK7 and CK19 in intrahepatic cholangiocarcinoma (ICC). METHODS: Immunohistochemistry was performed to assess CK7 and CK19 expression on tissue microarrays in training cohort enrolling 214 ICC patients and validation cohort comprising 108 ICC patients. Kaplan-Meier analysis, Cox's proportional hazards regression, and nomogram were applied to evaluate the prognostic significance of both CKs. RESULTS: Both CK7 and CK19 expression were significantly up-regulated in ICC compared to their non-tumor counterparts, and positively correlated with aggressive tumor phenotypes, like lymph node metastasis and larger tumor size. Furthermore, high expression of either CK7 or CK19 predicted a significantly dismal postoperative survival. Integrated analysis of CK7 and CK19 expression was identified as a better indicator for survival probability. Notably, the nomogram integrating CK7/CK19 index had a perfect prognostic performance as compared with current staging systems. The results were further confirmed in the validation cohort. CONCLUSIONS: CK7/CK19 index was an independent adverse prognostic factor for ICC patients' survival, and may be helpful to improve postoperative risk stratification and individualized treatment strategies.","Source":"PubMed","category":"HUMAN","training_data":"CK7/CK19 index: A potential prognostic factor for postoperative intrahepatic cholangiocarcinoma patients BACKGROUND AND OBJECTIVES: Frequently aberrant expression of cytokeratin 7 (CK7) and cytokeratin 19 (CK19) have been observed in several human cancers. In this retrospective study, we aimed at investigating the prognostic significance of CK7 and CK19 in intrahepatic cholangiocarcinoma (ICC). METHODS: Immunohistochemistry was performed to assess CK7 and CK19 expression on tissue microarrays in training cohort enrolling 214 ICC patients and validation cohort comprising 108 ICC patients. Kaplan-Meier analysis, Cox's proportional hazards regression, and nomogram were applied to evaluate the prognostic significance of both CKs. RESULTS: Both CK7 and CK19 expression were significantly up-regulated in ICC compared to their non-tumor counterparts, and positively correlated with aggressive tumor phenotypes, like lymph node metastasis and larger tumor size. Furthermore, high expression of either CK7 or CK19 predicted a significantly dismal postoperative survival. Integrated analysis of CK7 and CK19 expression was identified as a better indicator for survival probability. Notably, the nomogram integrating CK7/CK19 index had a perfect prognostic performance as compared with current staging systems. The results were further confirmed in the validation cohort. CONCLUSIONS: CK7/CK19 index was an independent adverse prognostic factor for ICC patients' survival, and may be helpful to improve postoperative risk stratification and individualized treatment strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"identification development gene signature predicting recurrence patients intrahepatic cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Identification And Development Of Gene Signature For Predicting Recurrence In Patients With Intrahepatic Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Identification And Development Of Gene Signature For Predicting Recurrence In Patients With Intrahepatic Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"role cancer associated myofibroblasts intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma typically characterized dense desmoplastic stroma cancer associated myofibroblasts express smooth muscle actin major cellular component stromal myofibroblasts crucial role accelerating progression intrahepatic cholangiocarcinoma promoting resistance therapy interactive autocrine paracrine signaling pathways promote malignant cell proliferation migration invasiveness apoptosis resistance epithelial mesenchymal transition changes correlate aggressive tumor behavior hypoxic desmoplasia aberrant hedgehog signaling stromal myofibroblastic cells cholangiocarcinoma cells also critical modulators intrahepatic cholangiocarcinoma progression therapy resistance novel strategy developed achieve improved therapeutic outcomes patients advanced intrahepatic cholangiocarcinoma based targeting multiple interactive pathways cancer associated myofibroblasts intrahepatic cholangiocarcinoma cells associated disease progression poor survival unique organotypic cell culture orthotopic rat models cholangiocarcinoma progression well suited rapid preclinical testing potentially paradigm shifting strategy google scholar","probabilities":0.9467213,"Title":"The Role Of Cancer-Associated Myofibroblasts In Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma is typically characterized by a dense desmoplastic stroma, of which cancer-associated myofibroblasts (which express α-smooth muscle actin), are a major cellular component. These stromal myofibroblasts have a crucial role in accelerating the progression of intrahepatic cholangiocarcinoma and in promoting resistance to therapy through interactive autocrine and paracrine signaling pathways that promote malignant cell proliferation, migration, invasiveness, apoptosis resistance and/or epithelial–mesenchymal transition. These changes correlate with aggressive tumor behavior. Hypoxic desmoplasia and aberrant Hedgehog signaling between stromal myofibroblastic cells and cholangiocarcinoma cells are also critical modulators of intrahepatic cholangiocarcinoma progression and therapy resistance. A novel strategy has been developed to achieve improved therapeutic outcomes in patients with advanced intrahepatic cholangiocarcinoma, based on targeting of multiple interactive pathways between cancer-associated myofibroblasts and intrahepatic cholangiocarcinoma cells that are associated with disease progression and poor survival. Unique organotypic cell culture and orthotopic rat models of cholangiocarcinoma progression are well suited to the rapid preclinical testing of this potentially paradigm-shifting strategy.","Source":"Google Scholar","category":"ANIMAL","training_data":"The Role Of Cancer-Associated Myofibroblasts In Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma is typically characterized by a dense desmoplastic stroma, of which cancer-associated myofibroblasts (which express α-smooth muscle actin), are a major cellular component. These stromal myofibroblasts have a crucial role in accelerating the progression of intrahepatic cholangiocarcinoma and in promoting resistance to therapy through interactive autocrine and paracrine signaling pathways that promote malignant cell proliferation, migration, invasiveness, apoptosis resistance and/or epithelial–mesenchymal transition. These changes correlate with aggressive tumor behavior. Hypoxic desmoplasia and aberrant Hedgehog signaling between stromal myofibroblastic cells and cholangiocarcinoma cells are also critical modulators of intrahepatic cholangiocarcinoma progression and therapy resistance. A novel strategy has been developed to achieve improved therapeutic outcomes in patients with advanced intrahepatic cholangiocarcinoma, based on targeting of multiple interactive pathways between cancer-associated myofibroblasts and intrahepatic cholangiocarcinoma cells that are associated with disease progression and poor survival. Unique organotypic cell culture and orthotopic rat models of cholangiocarcinoma progression are well suited to the rapid preclinical testing of this potentially paradigm-shifting strategy. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"second line systemic treatment advanced cholangiocarcinoma background gemcitabine plus platinum gem p combination chemotherapy standard treatment first line advanced cholangiocarcinoma acc gem p first line therapy reports progression free survival pfs 8 months overall survival os 11 7 months treatment second line setting less clear five year survival acc remains dismal 5 10 purpose study describe outcomes second line systemic treatment institution methods study single institution retrospective chart review acc patients initiated second line systemic treatment 1 1 2009 12 31 2012 primary objective evaluate pfs second line systemic treatment secondary objectives os disease control rate second line systemic regimens classified four treatment groups gem p gemcitabine fluoropyrimidine gem fu fu combination fu combo others results fifty six patients included majority intrahepatic acc total 80 received first line gemcitabine based therapy second line therapy consisted gem p 19 6 gem fu 28 6 fu combo 37 5 others 14 3 median pfs 2 7 month 95 ci 2 3 3 8 months median os 13 8 months 95 ci 12 19 3 months disease control rate 50 significant difference survival identified four treatment groups conclusions study revealed 2 7 month pfs 50 disease control rate potential survival benefit second line treatment options second line systemic therapy include gem fu fu combo gem p given first line setting targeted therapy erlotinib bevacizumab considered addition chemotherapy stn","probabilities":0.9799733,"Title":"Second-Line Systemic Treatment For Advanced Cholangiocarcinoma","Abstract":"Background: Gemcitabine plus platinum (GEM-P) combination chemotherapy is standard treatment for first-line advanced cholangiocarcinoma (aCC). GEM-P first-line therapy reports a progression-free survival (PFS) of 8 months and overall survival (OS) of 11.7 months. Treatment in the second-line setting is less clear. Five-year survival for aCC remains dismal at 5-10%. The purpose of this study was to describe the outcomes with second-line systemic treatment at our institution. \r\n\r\n Methods: This study was a single institution retrospective chart review of aCC patients who initiated second-line systemic treatment during 1/1/2009 to 12/31/2012. The primary objective was to evaluate PFS with second-line systemic treatment. Secondary objectives were OS and disease control rate. Second-line systemic regimens were classified into four treatment groups: GEM-P, gemcitabine + fluoropyrimidine (GEM-FU), other FU combination (FU-combo), and others. \r\n\r\n Results: Fifty-six patients were included and the majority had intrahepatic aCC. A total of 80% received first-line gemcitabine-based therapy. Second-line therapy consisted of GEM-P (19.6%), GEM-FU (28.6%), FU-combo (37.5%), and others (14.3%). Median PFS was 2.7-month (95% CI, 2.3-3.8 months) with a median OS of 13.8 months (95% CI, 12-19.3 months) and a disease control rate of 50%. No significant difference in survival was identified between the four treatment groups. \r\n\r\n Conclusions: This study revealed a 2.7-month PFS, 50% disease control rate, and potential survival benefit with second-line treatment. Options for second-line systemic therapy include GEM-FU, FU-combo, GEM-P if not given in the first-line setting. Targeted therapy with erlotinib or bevacizumab could be considered in addition to chemotherapy.","Source":"STN","category":"HUMAN","training_data":"Second-Line Systemic Treatment For Advanced Cholangiocarcinoma Background: Gemcitabine plus platinum (GEM-P) combination chemotherapy is standard treatment for first-line advanced cholangiocarcinoma (aCC). GEM-P first-line therapy reports a progression-free survival (PFS) of 8 months and overall survival (OS) of 11.7 months. Treatment in the second-line setting is less clear. Five-year survival for aCC remains dismal at 5-10%. The purpose of this study was to describe the outcomes with second-line systemic treatment at our institution. \r\n\r\n Methods: This study was a single institution retrospective chart review of aCC patients who initiated second-line systemic treatment during 1/1/2009 to 12/31/2012. The primary objective was to evaluate PFS with second-line systemic treatment. Secondary objectives were OS and disease control rate. Second-line systemic regimens were classified into four treatment groups: GEM-P, gemcitabine + fluoropyrimidine (GEM-FU), other FU combination (FU-combo), and others. \r\n\r\n Results: Fifty-six patients were included and the majority had intrahepatic aCC. A total of 80% received first-line gemcitabine-based therapy. Second-line therapy consisted of GEM-P (19.6%), GEM-FU (28.6%), FU-combo (37.5%), and others (14.3%). Median PFS was 2.7-month (95% CI, 2.3-3.8 months) with a median OS of 13.8 months (95% CI, 12-19.3 months) and a disease control rate of 50%. No significant difference in survival was identified between the four treatment groups. \r\n\r\n Conclusions: This study revealed a 2.7-month PFS, 50% disease control rate, and potential survival benefit with second-line treatment. Options for second-line systemic therapy include GEM-FU, FU-combo, GEM-P if not given in the first-line setting. Targeted therapy with erlotinib or bevacizumab could be considered in addition to chemotherapy. STN","prediction_labels":"HUMAN"},{"cleaned":"dna index prognostic tool hilar cholangiocarcinoma background objectives due devastating prognosis patients suffering hilar cholangiocarcinoma hcca valid prognostic factors urgently needed guide treatment decisions personalized concept aim study analyze predictive value dna index large single center cohort patients undergoing resection hcca methods total 154 patients underwent resection hcca included prospective study dna index assessed image cytometry fresh tumor samples correlated well standard histopathological parameters patient survival results median dna index 1 61 0 32 univariate survival analysis identified eight parameters including dna index dna ploidy prognostic markers cox proportional hazard model dna index p 0 021 tumor size p 0 029 lymph nodes status p 0 039 shown independent predictors patient survival conclusion dna index represents independent prognostic marker hcca superior standard histopathological factors since dna index assessed post also preoperatively might potential tool preoperative decision making process pubmed","probabilities":0.9799733,"Title":"The DNA index as a prognostic tool in hilar cholangiocarcinoma","Abstract":"BACKGROUND AND OBJECTIVES: Due to the devastating prognosis of patients suffering from hilar cholangiocarcinoma (HCCA) valid prognostic factors are urgently needed to guide treatment decisions in a personalized concept. The aim of this study was to analyze the predictive value of the DNA index in a large single-center cohort of patients undergoing resection of HCCA. METHODS: A total of 154 patients who underwent resection of HCCA were included in this prospective study. The DNA index was assessed by image cytometry of fresh tumor samples and correlated, as well as standard histopathological parameters, with patient survival. RESULTS: The median DNA index was 1.61 ± 0.32. Univariate survival analysis identified eight parameters including DNA index, but not DNA ploidy as prognostic markers. In the Cox proportional hazard model DNA index (P = 0.021), tumor size (P = 0.029) and lymph nodes status (P = 0.039) could be shown to be independent predictors of patient survival. CONCLUSION: The DNA index represents an independent prognostic marker in HCCA which is superior to most standard histopathological factors. Since the DNA index can be assessed not only post- but also preoperatively, it might be a potential tool in the preoperative decision-making process.","Source":"PubMed","category":"HUMAN","training_data":"The DNA index as a prognostic tool in hilar cholangiocarcinoma BACKGROUND AND OBJECTIVES: Due to the devastating prognosis of patients suffering from hilar cholangiocarcinoma (HCCA) valid prognostic factors are urgently needed to guide treatment decisions in a personalized concept. The aim of this study was to analyze the predictive value of the DNA index in a large single-center cohort of patients undergoing resection of HCCA. METHODS: A total of 154 patients who underwent resection of HCCA were included in this prospective study. The DNA index was assessed by image cytometry of fresh tumor samples and correlated, as well as standard histopathological parameters, with patient survival. RESULTS: The median DNA index was 1.61 ± 0.32. Univariate survival analysis identified eight parameters including DNA index, but not DNA ploidy as prognostic markers. In the Cox proportional hazard model DNA index (P = 0.021), tumor size (P = 0.029) and lymph nodes status (P = 0.039) could be shown to be independent predictors of patient survival. CONCLUSION: The DNA index represents an independent prognostic marker in HCCA which is superior to most standard histopathological factors. Since the DNA index can be assessed not only post- but also preoperatively, it might be a potential tool in the preoperative decision-making process. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role lymph nodes predicting prognosis ampullary carcinoma curative resection background lymph node involvement one well demonstrated prognostic factors ampullary carcinoma aim study clarify role lymph nodes predicting survival outcome ampullary carcinoma methods cohort consecutive curative pancreaticoduodenectomies ampullary carcinoma 1999 2014 retrospectively analyzed effect node associated variables including lymph node status positive lymph node number total harvested lymph node thln number lymph node ratio lnr examined using univariate multivariate analyses survival outcome prediction results 194 evaluable patients univariate analysis demonstrated stage cell differentiation perineural invasion nodal status significant conventional prognostic factors concerning node associated variables positive nodal status positive lymph node number 2 thln number 14 lnr 0 15 significantly associated poorer survival outcomes 5 year survival rate 20 3 38 9 25 4 18 respectively multivariate analysis nodal status thln number two independent predictors survival favorable 5 year survival rate 84 4 patients negative nodal involvement thln number 14 compared poorest 5 year survival rate 16 1 positive nodal status thln number 14 conclusions tumor biology reflected lymph node status important independent prognostic factor nevertheless surgical radicality based thln number also plays significant role survival outcome patients ampullary carcinoma curative pancreaticoduodenectomy pubmed","probabilities":0.962963,"Title":"The role of lymph nodes in predicting the prognosis of ampullary carcinoma after curative resection","Abstract":"BACKGROUND: Lymph node involvement is one of the well-demonstrated prognostic factors in ampullary carcinoma. The aim of this study is to clarify the role of lymph nodes in predicting the survival outcome of ampullary carcinoma. METHODS: A cohort of consecutive curative pancreaticoduodenectomies for ampullary carcinoma from 1999 to 2014 was retrospectively analyzed. The effect of node-associated variables, including lymph node status, positive lymph node number, total harvested lymph node (THLN) number, and lymph node ratio (LNR) was examined using univariate and multivariate analyses for survival outcome prediction. RESULTS: In 194 evaluable patients, univariate analysis demonstrated that stage, cell differentiation, perineural invasion, and nodal status were significant conventional prognostic factors. Concerning the node-associated variables, positive nodal status, positive lymph node number≥2, THLN number<14, and LNR≥0.15 were significantly associated with poorer survival outcomes, with a 5-year survival rate of 20.3, 38.9, 25.4, and 18%, respectively. By multivariate analysis, nodal status and THLN number were two independent predictors of survival. The most favorable 5-year survival rate was 84.4% in patients with negative nodal involvement and THLN number≥14, compared with the poorest 5-year survival rate of 16.1% in those with positive nodal status and THLN number<14. CONCLUSIONS: Tumor biology reflected by lymph node status is the most important independent prognostic factor; nevertheless, surgical radicality based on THLN number also plays a significant role in the survival outcome for patients with ampullary carcinoma after curative pancreaticoduodenectomy.","Source":"PubMed","category":"HUMAN","training_data":"The role of lymph nodes in predicting the prognosis of ampullary carcinoma after curative resection BACKGROUND: Lymph node involvement is one of the well-demonstrated prognostic factors in ampullary carcinoma. The aim of this study is to clarify the role of lymph nodes in predicting the survival outcome of ampullary carcinoma. METHODS: A cohort of consecutive curative pancreaticoduodenectomies for ampullary carcinoma from 1999 to 2014 was retrospectively analyzed. The effect of node-associated variables, including lymph node status, positive lymph node number, total harvested lymph node (THLN) number, and lymph node ratio (LNR) was examined using univariate and multivariate analyses for survival outcome prediction. RESULTS: In 194 evaluable patients, univariate analysis demonstrated that stage, cell differentiation, perineural invasion, and nodal status were significant conventional prognostic factors. Concerning the node-associated variables, positive nodal status, positive lymph node number≥2, THLN number<14, and LNR≥0.15 were significantly associated with poorer survival outcomes, with a 5-year survival rate of 20.3, 38.9, 25.4, and 18%, respectively. By multivariate analysis, nodal status and THLN number were two independent predictors of survival. The most favorable 5-year survival rate was 84.4% in patients with negative nodal involvement and THLN number≥14, compared with the poorest 5-year survival rate of 16.1% in those with positive nodal status and THLN number<14. CONCLUSIONS: Tumor biology reflected by lymph node status is the most important independent prognostic factor; nevertheless, surgical radicality based on THLN number also plays a significant role in the survival outcome for patients with ampullary carcinoma after curative pancreaticoduodenectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors patients pt2 gallbladder carcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Prognostic Factors Of Patients With Pt2 Gallbladder Carcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Factors Of Patients With Pt2 Gallbladder Carcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"postoperative mortality liver resection perihilar cholangiocarcinoma importance biliary drainage future liver remnant development risk score background liver surgery perihilar cholangiocarcinoma phc associated postoperative mortality ranging 5 18 aim study develop preoperative risk score postoperative mortality liver resection phc assess effect biliary drainage future liver remnant flr study design consecutive series 287 patients submitted major liver resection presumed phc 1997 2014 2 western centers analyzed 228 patients 79 underwent preoperative drainage jaundice future liver remnant volumes calculated ct volumetry completeness flr drainage assessed imaging logistic regression used develop mortality risk score results postoperative mortality 90 days 14 independently predicted age odds ratio per 10 years 2 1 preoperative cholangitis 4 1 flr volume 30 2 9 portal vein reconstruction 2 3 incomplete flr drainage patients flr volume 50 2 8 risk score showed good discrimination area curve 0 75 bootstrap validation ranking patients tertiles identified 3 ie low intermediate high risk subgroups predicted mortalities 2 11 37 postoperative mortality observed 33 undrained patients flr volumes 50 including 10 jaundiced patients median bilirubin level 11 mg dl conclusions mortality risk score patients resectable phc used patient counseling identification modifiable risk factors include flr volume flr drainage status preoperative cholangitis found evidence support preoperative biliary drainage patients flr volume 50 stn","probabilities":0.9799733,"Title":"Postoperative Mortality After Liver Resection For Perihilar Cholangiocarcinoma: Importance Of Biliary Drainage Of The Future Liver Remnant And Development Of A Risk Score","Abstract":"Background: Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR). \r\n\r\n Study design: A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score. \r\n\r\n Results: Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio [OR] per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume <30% (OR = 2.9), portal vein reconstruction (OR = 2.3), and incomplete FLR drainage in patients with FLR volume <50% (OR = 2.8). The risk score showed good discrimination (area under the curve = 0.75 after bootstrap validation) and ranking patients in tertiles identified 3 (ie low, intermediate, and high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes >50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL). \r\n\r\n Conclusions: The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume >50%.","Source":"STN","category":"HUMAN","training_data":"Postoperative Mortality After Liver Resection For Perihilar Cholangiocarcinoma: Importance Of Biliary Drainage Of The Future Liver Remnant And Development Of A Risk Score Background: Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR). \r\n\r\n Study design: A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score. \r\n\r\n Results: Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio [OR] per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume <30% (OR = 2.9), portal vein reconstruction (OR = 2.3), and incomplete FLR drainage in patients with FLR volume <50% (OR = 2.8). The risk score showed good discrimination (area under the curve = 0.75 after bootstrap validation) and ranking patients in tertiles identified 3 (ie low, intermediate, and high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes >50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL). \r\n\r\n Conclusions: The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume >50%. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact controlling nutritional status conut intrahepatic cholangiocarcinoma following curative hepatectomy retrospective single institution study background several studies examined controlling nutritional status conut one useful biomarkers predicting patients prognosis following cancer treatment aim study evaluate value conut postoperative prognostic marker patients intrahepatic cholangiocarcinoma icc following curative hepatectomy methods retrospectively analyzed 71 patients underwent curative hepatectomy icc may 2002 november 2016 patients divided two groups according preoperative conut score e conut 2 conut 2 results number patients assigned normal mild moderate severe malnutrition groups 40 28 two one respectively high conut group conut 2 consisted 31 patients 43 7 poor prognosis regard overall survival os p 0 0149 high conut score also identified one independent predictors poor prognosis os hazard ratio 3 02 95 confidence interval 1 4 6 8 p 0 007 however current study high conut score associated postoperative complications clavien dindo classification iii conclusions conut may useful preoperative assessment prognosis patients icc undergone curative hepatectomy pubmed","probabilities":0.9799733,"Title":"The Prognostic Impact of Controlling Nutritional Status (CONUT) in Intrahepatic Cholangiocarcinoma Following Curative Hepatectomy: A Retrospective Single Institution Study","Abstract":"BACKGROUND: Several studies have examined controlling nutritional status (CONUT), which is one of the useful biomarkers for predicting patients' prognosis following cancer treatment. The aim of this study was to evaluate the value of CONUT as a postoperative prognostic marker in patients with intrahepatic cholangiocarcinoma (ICC) following curative hepatectomy. METHODS: We retrospectively analyzed 71 patients who underwent curative hepatectomy for ICC between May 2002 and November 2016. Patients were divided into two groups according to their preoperative CONUT score (i.e., CONUT ≧ 2 or CONUT < 2). RESULTS: The number of patients assigned to the normal, mild, moderate, or severe malnutrition groups was 40, 28, two, and one, respectively. The high CONUT group (CONUT ≧ 2) consisted of 31 patients (43.7%) and had a poor prognosis with regard to overall survival (OS) (p = 0.0149). A high CONUT score is also identified as one of the independent predictors of poor prognosis in OS (hazard ratio 3.02; 95% confidence interval 1.4-6.8; p = 0.007). However, in the current study, a high CONUT score was not associated with postoperative complications (Clavien-Dindo classification ≧ III or more). CONCLUSIONS: CONUT may be useful for the preoperative assessment of prognosis in patients with ICC who have undergone curative hepatectomy.","Source":"PubMed","category":"HUMAN","training_data":"The Prognostic Impact of Controlling Nutritional Status (CONUT) in Intrahepatic Cholangiocarcinoma Following Curative Hepatectomy: A Retrospective Single Institution Study BACKGROUND: Several studies have examined controlling nutritional status (CONUT), which is one of the useful biomarkers for predicting patients' prognosis following cancer treatment. The aim of this study was to evaluate the value of CONUT as a postoperative prognostic marker in patients with intrahepatic cholangiocarcinoma (ICC) following curative hepatectomy. METHODS: We retrospectively analyzed 71 patients who underwent curative hepatectomy for ICC between May 2002 and November 2016. Patients were divided into two groups according to their preoperative CONUT score (i.e., CONUT ≧ 2 or CONUT < 2). RESULTS: The number of patients assigned to the normal, mild, moderate, or severe malnutrition groups was 40, 28, two, and one, respectively. The high CONUT group (CONUT ≧ 2) consisted of 31 patients (43.7%) and had a poor prognosis with regard to overall survival (OS) (p = 0.0149). A high CONUT score is also identified as one of the independent predictors of poor prognosis in OS (hazard ratio 3.02; 95% confidence interval 1.4-6.8; p = 0.007). However, in the current study, a high CONUT score was not associated with postoperative complications (Clavien-Dindo classification ≧ III or more). CONCLUSIONS: CONUT may be useful for the preoperative assessment of prognosis in patients with ICC who have undergone curative hepatectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"body mass index diabetes intrahepatic cholangiocarcinoma risk liver cancer pooling project meta analysis objective obesity diabetes associated increased liver cancer risk however studies examined primary liver cancers hepatocellular carcinoma studies evaluating intrahepatic cholangiocarcinoma icc second common type liver cancer thus examined association obesity diabetes icc risk pooled analysis conducted systematic review meta analysis literature design pooled analysis utilized liver cancer pooling project consortium 13 us based prospective cohort studies data 1 541 143 individuals icc cases n 414 systematic review identified 14 additional studies conducted meta analysis combining results lcpp results 5 prospective studies identified september 2017 results lcpp obesity diabetes associated 62 hazard ratio hr 1 62 95 confidence interval ci 1 24 2 12 81 hr 1 81 95 ci 1 33 2 46 increased icc risk respectively meta analysis prospectively ascertained cohorts nested case control studies obesity associated 49 increased icc risk relative risk rr 1 49 95 ci 1 32 1 70 n 4 studies 2 0 diabetes associated 53 increased icc risk rr 1 53 95 ci 1 31 1 78 n 6 studies noted heterogeneity studies 2 67 diabetes results consistent subgroup analyses results hospital based case control studies n 9 mostly consistent studies potentially subject reverse causation conclusions findings suggest obesity diabetes associated increased icc risk highlighting similar etiologies hepatocellular carcinoma intrahepatic cholangiocarcinoma however additional prospective studies needed verify associations pubmed","probabilities":0.9799733,"Title":"Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis","Abstract":"OBJECTIVE: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature. DESIGN: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC cases n = 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017. RESULTS: In the LCPP, obesity and diabetes were associated with a 62% [Hazard Ratio (HR) = 1.62, 95% Confidence Interval (CI): 1.24-2.12] and an 81% (HR = 1.81, 95% CI: 1.33-2.46) increased ICC risk, respectively. In the meta-analysis of prospectively ascertained cohorts and nested case-control studies, obesity was associated with a 49% increased ICC risk [Relative Risk (RR) = 1.49, 95% CI: 1.32-1.70; n = 4 studies; I(2) = 0%]. Diabetes was associated with a 53% increased ICC risk (RR = 1.53, 95% CI: 1.31-1.78; n = 6 studies). While we noted heterogeneity between studies (I(2) = 67%) for diabetes, results were consistent in subgroup analyses. Results from hospital-based case-control studies (n = 9) were mostly consistent, but these studies are potentially subject to reverse causation. CONCLUSIONS: These findings suggest that obesity and diabetes are associated with increased ICC risk, highlighting similar etiologies of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, additional prospective studies are needed to verify these associations.","Source":"PubMed","category":"HUMAN","training_data":"Body Mass Index, Diabetes and Intrahepatic Cholangiocarcinoma Risk: The Liver Cancer Pooling Project and Meta-analysis OBJECTIVE: Obesity and diabetes are associated with an increased liver cancer risk. However, most studies have examined all primary liver cancers or hepatocellular carcinoma, with few studies evaluating intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. Thus, we examined the association between obesity and diabetes and ICC risk in a pooled analysis and conducted a systematic review/meta-analysis of the literature. DESIGN: For the pooled analysis, we utilized the Liver Cancer Pooling Project, a consortium of 13 US-based, prospective cohort studies with data from 1,541,143 individuals (ICC cases n = 414). In our systematic review, we identified 14 additional studies. We then conducted a meta-analysis, combining the results from LCPP with results from the 5 prospective studies identified through September 2017. RESULTS: In the LCPP, obesity and diabetes were associated with a 62% [Hazard Ratio (HR) = 1.62, 95% Confidence Interval (CI): 1.24-2.12] and an 81% (HR = 1.81, 95% CI: 1.33-2.46) increased ICC risk, respectively. In the meta-analysis of prospectively ascertained cohorts and nested case-control studies, obesity was associated with a 49% increased ICC risk [Relative Risk (RR) = 1.49, 95% CI: 1.32-1.70; n = 4 studies; I(2) = 0%]. Diabetes was associated with a 53% increased ICC risk (RR = 1.53, 95% CI: 1.31-1.78; n = 6 studies). While we noted heterogeneity between studies (I(2) = 67%) for diabetes, results were consistent in subgroup analyses. Results from hospital-based case-control studies (n = 9) were mostly consistent, but these studies are potentially subject to reverse causation. CONCLUSIONS: These findings suggest that obesity and diabetes are associated with increased ICC risk, highlighting similar etiologies of hepatocellular carcinoma and intrahepatic cholangiocarcinoma. However, additional prospective studies are needed to verify these associations. PubMed","prediction_labels":"HUMAN"},{"cleaned":"italian cancer figures report 2013 multiple tumours objectives collaborative study based data collected network italian association cancer registries airtum provides updated estimates incidence risk multiple primary cancer mp objective highlight quantify bidirectional associations different oncological diseases quantification excess decreased risk cancers cancer patients comparison general population may contribute understand aetiology cancer address clinical follow material methods data herein presented provided airtum population based cancer registries cover nowadays 48 italian population monograph utilizes airtum database december 2012 considering malignant cancer cases diagnosed 1976 2010 cases coded according icd o 3 non melanoma skin cancer cases cases based death certificate cases based autopsy cases follow time equal zero excluded define multiple primaries iarc iacr rules adopted http www iacr com fr mprules_july2004 pdf data subjected standard quality control procedures described airtum data management protocol specific quality control checks defined present study cohort cancer patients followed time first cancer diagnosis date second cancer diagnosis death end follow evaluate whether number observed second cancer cases greater expected person years risk py computed first cancer site geographic area north centre south islands attained age attained calendar year group second cancers diagnosed cohort patients included observed numbers cases expected number cancer cases computed multiplying accumulated py expected rates calculated airtum database stratified cancer site geographic area age calendar year group standardized incidence ratio sir calculated ratio observed expected cancer cases excess absolute risk ear beyond expected amount calculated subtracting expected number subsequent cancers observed number cancer cases difference divided py number cancer cases excess deficit expressed per 1 000 py confidence intervals stated 95 two months 60 days first cancer diagnosis defined synchronicity period main analysis observed expected cases period excluded estimated excess risk period first diagnosis 0 months excluding synchronicity period 2 months following periods 2 11 12 59 60 119 120 months diagnosis first cancer site gender specific sheets presented reporting sirs ears results 5 979 338 person years cohort 1 635 060 cancer patients 880 361 males 754 699 females diagnosed 1976 2010 followed mean follow length 14 years overall 85 399 metachronous latency 2 months cancers observed 77 813 expected study period sir 1 10 95 ci 1 09 1 10 ear 1 32 x 1 000 person years 95 ci 1 19 1 46 sir 1 08 95 ci 1 08 1 09 men 54 518 observed 50 260 expected 1 12 95 ci 1 11 1 13 women 30 881 27 553 ear 1 61 95 ci 1 37 1 84 1 08 x 1 000 person years 95 ci 0 93 1 24 respectively moreover first two months first cancer diagnosis synchronous period 14 807 cancers observed 3 536 expected sir 4 16 95 ci 4 09 4 22 sir 4 08 95 ci 4 00 4 16 men 4 32 95 ci 4 20 4 45 women mean age patients first cancer diagnosis 67 0 years among males 65 8 among females risk mp related age higher younger patients lower older ones relation time first cancer diagnosis sir high beginning decreased although remaining constantly 1 rose time strong differences evident across different incidence periods showed increased mp risk women higher sirs expected 18 cancer sites men 12 statistically significantly sirs lower 1 2 8 respectively increased overall mp risk observed patients sexes first primary oral cavity sir men 1 93 sir women 1 48 pharynx sir men 2 13 sir women 1 99 larynx sir men 1 57 sir women 1 79 oesophagus sir men 1 45 sir women 1 41 lung sir men 1 09 sir women 1 13 kidney sir men 1 14 sir women 1 15 urinary bladder sir men 1 29 sir women 1 22 thyroid sir 1 22 sexes hodgkin lymphoma sir men 1 59 sir women 1 94 non hodgkin lymphoma sir men 1 13 sir women 1 12 heterogeneous group sites sir men 1 09 sir women 1 07 moreover men higher mp risk first cancer testis sir 1 24 true women gallbladder sir 1 21 skin melanoma sir 1 17 bone sir 1 41 breast sir 1 12 cervix uteri sir 1 23 corpus uteri sir 1 23 ovarian cancer sir 1 18 contrary first liver pancreas cancer associated decreased mp risk sexes liver sir 0 86 0 81 men women respectively pancreas sir 0 70 0 78 men women respectively colon sir 0 93 rectum sir 0 83 gallbladder sir 0 80 prostate sir 0 93 mesothelioma sir 0 65 central nervous system sir 0 82 among men among cancers ear statistically significant higher excess absolute risk mp oral cavity ear 16 0 x 1 000 person years men 5 4 women pharynx 17 6 9 1 larynx 11 4 8 8 oesophagus 8 5 4 8 discussion descriptive study provides quantitative information risk developing second cancer italian population based cohort approximately 1 65 million cancer patients compared risk general population follow time average 14 years cancer patients mp risk 10 higher comparison general population excess absolute risk 1 32 x 1 000 person years study mps risk measures dependent methods used calculation definition mp univocal using different rules greatly change number cancers patient mps however airtum cancer registries adopt recommendations mp definition monograph therefore made possible shared rules standards used airtum registries cancer site specific sheets represent core monograph useful highlight quantify bidirectional associations among different diseases therefore provide indications clinical follow lifestyle changes healthful directions positive effect cancer patient population always recommended pubmed","probabilities":0.9799733,"Title":"Italian cancer figures, report 2013: Multiple tumours","Abstract":"OBJECTIVES: This collaborative study, based on data collected by the network of Italian association of cancer registries (AIRTUM), provides updated estimates on the incidence risk of multiple primary cancer (MP). The objective is to highlight and quantify the bidirectional associations between different oncological diseases. The quantification of the excess or decreased risk of further cancers in cancer patients, in comparison with the general population, may contribute to understand the aetiology of cancer and to address clinical follow-up. MATERIAL AND METHODS: Data herein presented were provided by AIRTUM population-based cancer registries, which cover nowadays 48% of the Italian population. This monograph utilizes the AIRTUM database (December 2012), considering all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to ICD-O-3. Non-melanoma skin cancer cases, cases based on death certificate only, cases based on autopsy only, and cases with follow-up time equal to zero were excluded. To define multiple primaries, IARC-IACR rules were adopted (http://www.iacr.com.fr/MPrules_july2004.pdf). Data were subjected to standard quality control procedures (described in the AIRTUM data management protocol) and specific quality control checks defined for the present study. A cohort of cancer patients was followed over time from first cancer diagnosis until the date of second cancer diagnosis, death, or the end of follow-up, to evaluate whether the number of observed second cancer cases was greater than expected. Person years at risk (PY) were computed by first cancer site, geographic area (North, Centre, South and Islands), attained age, and attained calendar-year group. All second cancers diagnosed in the cohort's patients were included in the observed numbers of cases. The expected number of cancer cases was computed multiplying the accumulated PY by the expected rates, calculated from the AIRTUM database stratified by cancer site, geographic area, age, and calendar-year group. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cancer cases. The Excess Absolute Risk (EAR) beyond the expected amount were calculated subtracting the expected number of subsequent cancers from the observed number of cancer cases; the difference was then divided by the PY and the number of cancer cases in excess (or deficit) was expressed per 1,000 PY. Confidence intervals were stated at 95%. The two months (60 days) after first cancer diagnosis were defined as \"synchronicity period\", and in the main analysis observed and expected cases during this period were excluded. It was estimated the excess risk in the period after first diagnosis (≥ 0 months), excluding the synchronicity period (≥ 2 months), and during the following periods: 2-11, 12-59, 60-119 and 120 months after diagnosis. First-cancer-site-and-gender-specific sheets are presented, reporting both SIRs and EARs. RESULTS: For 5,979,338 person-years a cohort of 1,635,060 cancer patients (880,361 males and 754,699 females) diagnosed between 1976 and 2010 was followed. The mean follow-up length was 14 years. Overall, 85,399 metachronous (latency ≥2 months) cancers were observed, while 77,813 were expected during the study period: SIR: 1.10 (95%CI 1.09-1.10), EAR: 1.32 x 1,000 person-years (95%CI 1.19 - 1.46). The SIR was 1.08 (95%CI 1.08-1.09) for men (54,518 observed and 50,260 expected) and 1.12 (95%CI 1.11-1.13) for women (30,881/27,553), and the EAR 1.61 (95%CI 1.37-1.84) and 1.08 x 1,000 person-years (95%CI 0.93-1.24), respectively.Moreover, during the first two months after first cancer diagnosis (synchronous period) 14,807 cancers were observed while 3,536 were expected (SIR: 4.16; 95%CI 4.09-4.22); the SIR was 4.08 (95%CI 4.00-4.16) for men and 4.32 (95%CI 4.20-4.45) for women.The mean age of patients at first cancer diagnosis was 67.0 years among males and 65.8 among females.The risk of MP was related to age being higher for younger patients and lower for older ones. In relation to the time of first cancer diagnosis, the SIR was very high at the beginning and then decreased, although remaining constantly over 1, and then rose over time. No strong differences were evident across the different incidence periods, which all showed an increased MP risk.Women had higher SIRs than expected for 18 cancer sites, men for 12. The statistically significantly SIRs lower than 1 were 2 and 8, respectively. Increased overall MP risk was observed for patients of both sexes with a first primary in the oral cavity (SIR men: 1.93; SIR women: 1.48), pharynx (SIR men: 2.13; SIR women: 1.99), larynx (SIR men: 1.57; SIR women: 1.79), oesophagus (SIR men: 1.45; SIR women: 1.41), lung (SIR men: 1.09; SIR women: 1.13), kidney (SIR men: 1.14; SIR women: 1.15), urinary bladder (SIR men: 1.29; SIR women: 1.22), thyroid (SIR: 1.22 in both sexes), Hodgkin lymphoma (SIR men: 1.59; SIR women: 1.94), and non-Hodgkin lymphoma (SIR men: 1.13; SIR women: 1.12), and for the heterogeneous group \"other sites\" (SIR men: 1.09; SIR women: 1.07). Moreover, men had a higher MP risk if the first cancer was in the testis (SIR: 1.24), while the same was true for women with gallbladder (SIR: 1.21), skin melanoma (SIR: 1.17), bone (SIR: 1.41), breast (SIR: 1.12), cervix uteri (SIR: 1.23) and corpus uteri (SIR: 1.23), and ovarian cancer (SIR: 1.18). On the contrary, a first liver or pancreas cancer were associated with a decreased MP risk in both sexes (liver SIR: 0.86 and 0.81 for men and women, respectively; pancreas SIR: 0.70 and 0.78 for men and women, respectively), as were those of colon (SIR: 0.93), rectum (SIR: 0.83), gallbladder (SIR: 0.80), prostate (SIR: 0.93), mesothelioma (SIR: 0.65), and central nervous system (SIR: 0.82) among men. Among the cancers for which the EAR is statistically significant, those with higher Excess Absolute Risk of MP were those of the oral cavity (EAR: 16.0 x 1,000 person-years in men and 5.4 in women), pharynx (17.6 and 9.1), larynx (11.4 and 8.8), and oesophagus (8.5 and 4.8). DISCUSSION: This descriptive study provides quantitative information on the risk of developing a second cancer in an Italian population-based cohort of approximately 1.65 million cancer patients, compared to the risk of the general population. During the follow-up time (on average 14 years) cancer patients had an MP risk that was 10% higher in comparison to the general population and an Excess Absolute Risk of 1.32 x 1,000 person-years. Study of MPs and their risk measures are dependent on methods used in the calculation. The definition of MP is not univocal and using different rules can greatly change the number of cancers in a patient with MPs. However, the AIRTUM cancer registries adopt the same recommendations for MP definition. This monograph was therefore made possible by the shared rules and standards used by AIRTUM registries. The cancer site-specific sheets, which represent the core of the monograph, can be useful to highlight and quantify the bidirectional associations among different diseases and therefore provide indications for clinical follow-up. Lifestyle changes in more healthful directions can have a positive effect in the cancer patient population and should always be recommended.","Source":"PubMed","category":"HUMAN","training_data":"Italian cancer figures, report 2013: Multiple tumours OBJECTIVES: This collaborative study, based on data collected by the network of Italian association of cancer registries (AIRTUM), provides updated estimates on the incidence risk of multiple primary cancer (MP). The objective is to highlight and quantify the bidirectional associations between different oncological diseases. The quantification of the excess or decreased risk of further cancers in cancer patients, in comparison with the general population, may contribute to understand the aetiology of cancer and to address clinical follow-up. MATERIAL AND METHODS: Data herein presented were provided by AIRTUM population-based cancer registries, which cover nowadays 48% of the Italian population. This monograph utilizes the AIRTUM database (December 2012), considering all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to ICD-O-3. Non-melanoma skin cancer cases, cases based on death certificate only, cases based on autopsy only, and cases with follow-up time equal to zero were excluded. To define multiple primaries, IARC-IACR rules were adopted (http://www.iacr.com.fr/MPrules_july2004.pdf). Data were subjected to standard quality control procedures (described in the AIRTUM data management protocol) and specific quality control checks defined for the present study. A cohort of cancer patients was followed over time from first cancer diagnosis until the date of second cancer diagnosis, death, or the end of follow-up, to evaluate whether the number of observed second cancer cases was greater than expected. Person years at risk (PY) were computed by first cancer site, geographic area (North, Centre, South and Islands), attained age, and attained calendar-year group. All second cancers diagnosed in the cohort's patients were included in the observed numbers of cases. The expected number of cancer cases was computed multiplying the accumulated PY by the expected rates, calculated from the AIRTUM database stratified by cancer site, geographic area, age, and calendar-year group. The Standardized Incidence Ratio (SIR) was calculated as the ratio of observed to expected cancer cases. The Excess Absolute Risk (EAR) beyond the expected amount were calculated subtracting the expected number of subsequent cancers from the observed number of cancer cases; the difference was then divided by the PY and the number of cancer cases in excess (or deficit) was expressed per 1,000 PY. Confidence intervals were stated at 95%. The two months (60 days) after first cancer diagnosis were defined as \"synchronicity period\", and in the main analysis observed and expected cases during this period were excluded. It was estimated the excess risk in the period after first diagnosis (≥ 0 months), excluding the synchronicity period (≥ 2 months), and during the following periods: 2-11, 12-59, 60-119 and 120 months after diagnosis. First-cancer-site-and-gender-specific sheets are presented, reporting both SIRs and EARs. RESULTS: For 5,979,338 person-years a cohort of 1,635,060 cancer patients (880,361 males and 754,699 females) diagnosed between 1976 and 2010 was followed. The mean follow-up length was 14 years. Overall, 85,399 metachronous (latency ≥2 months) cancers were observed, while 77,813 were expected during the study period: SIR: 1.10 (95%CI 1.09-1.10), EAR: 1.32 x 1,000 person-years (95%CI 1.19 - 1.46). The SIR was 1.08 (95%CI 1.08-1.09) for men (54,518 observed and 50,260 expected) and 1.12 (95%CI 1.11-1.13) for women (30,881/27,553), and the EAR 1.61 (95%CI 1.37-1.84) and 1.08 x 1,000 person-years (95%CI 0.93-1.24), respectively.Moreover, during the first two months after first cancer diagnosis (synchronous period) 14,807 cancers were observed while 3,536 were expected (SIR: 4.16; 95%CI 4.09-4.22); the SIR was 4.08 (95%CI 4.00-4.16) for men and 4.32 (95%CI 4.20-4.45) for women.The mean age of patients at first cancer diagnosis was 67.0 years among males and 65.8 among females.The risk of MP was related to age being higher for younger patients and lower for older ones. In relation to the time of first cancer diagnosis, the SIR was very high at the beginning and then decreased, although remaining constantly over 1, and then rose over time. No strong differences were evident across the different incidence periods, which all showed an increased MP risk.Women had higher SIRs than expected for 18 cancer sites, men for 12. The statistically significantly SIRs lower than 1 were 2 and 8, respectively. Increased overall MP risk was observed for patients of both sexes with a first primary in the oral cavity (SIR men: 1.93; SIR women: 1.48), pharynx (SIR men: 2.13; SIR women: 1.99), larynx (SIR men: 1.57; SIR women: 1.79), oesophagus (SIR men: 1.45; SIR women: 1.41), lung (SIR men: 1.09; SIR women: 1.13), kidney (SIR men: 1.14; SIR women: 1.15), urinary bladder (SIR men: 1.29; SIR women: 1.22), thyroid (SIR: 1.22 in both sexes), Hodgkin lymphoma (SIR men: 1.59; SIR women: 1.94), and non-Hodgkin lymphoma (SIR men: 1.13; SIR women: 1.12), and for the heterogeneous group \"other sites\" (SIR men: 1.09; SIR women: 1.07). Moreover, men had a higher MP risk if the first cancer was in the testis (SIR: 1.24), while the same was true for women with gallbladder (SIR: 1.21), skin melanoma (SIR: 1.17), bone (SIR: 1.41), breast (SIR: 1.12), cervix uteri (SIR: 1.23) and corpus uteri (SIR: 1.23), and ovarian cancer (SIR: 1.18). On the contrary, a first liver or pancreas cancer were associated with a decreased MP risk in both sexes (liver SIR: 0.86 and 0.81 for men and women, respectively; pancreas SIR: 0.70 and 0.78 for men and women, respectively), as were those of colon (SIR: 0.93), rectum (SIR: 0.83), gallbladder (SIR: 0.80), prostate (SIR: 0.93), mesothelioma (SIR: 0.65), and central nervous system (SIR: 0.82) among men. Among the cancers for which the EAR is statistically significant, those with higher Excess Absolute Risk of MP were those of the oral cavity (EAR: 16.0 x 1,000 person-years in men and 5.4 in women), pharynx (17.6 and 9.1), larynx (11.4 and 8.8), and oesophagus (8.5 and 4.8). DISCUSSION: This descriptive study provides quantitative information on the risk of developing a second cancer in an Italian population-based cohort of approximately 1.65 million cancer patients, compared to the risk of the general population. During the follow-up time (on average 14 years) cancer patients had an MP risk that was 10% higher in comparison to the general population and an Excess Absolute Risk of 1.32 x 1,000 person-years. Study of MPs and their risk measures are dependent on methods used in the calculation. The definition of MP is not univocal and using different rules can greatly change the number of cancers in a patient with MPs. However, the AIRTUM cancer registries adopt the same recommendations for MP definition. This monograph was therefore made possible by the shared rules and standards used by AIRTUM registries. The cancer site-specific sheets, which represent the core of the monograph, can be useful to highlight and quantify the bidirectional associations among different diseases and therefore provide indications for clinical follow-up. Lifestyle changes in more healthful directions can have a positive effect in the cancer patient population and should always be recommended. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumor budding intrahepatic cholangiocarcinoma predictor postsurgery outcomes intrahepatic cholangiocarcinoma icc extremely aggressive carcinoma useful predictors patients prognosis surgery fully established university tokyo hospital pathology archives reviewed 107 cases icc 54 cases perihilar cholangiocarcinoma 40 cases extrahepatic cholangiocarcinoma ecc also investigated significance tumor budding icc comparison perihilar cholangiocarcinoma ecc tumor budding frequencies different tumor location 40 2 43 107 icc 70 4 38 54 perihilar cholangiocarcinoma 60 0 24 40 ecc tumor budding icc associated many pathologic indicators associated invasion major vascular invasion p 0 012 union international cancer control stage p 0 007 univariate multivariate cox regression analyses revealed tumor budding powerful prognostic factor recurrence free survival rfs overall survival os icc univariate rfs hazard ratio hr 2 666 95 confidence interval ci 1 517 4 683 os hr 4 206 95 ci 2 447 7 230 multivariate analyses rfs hr 3 038 95 ci 1 591 5 973 os hr 4 547 95 ci 2 348 8 805 tumor budding also significant prognostic factor perihilar cholangiocarcinoma ecc icc divided 2 subtypes type 1 hilar type 2 peripheral tumor budding strong prognostic factor type 2 icc type 1 icc suggesting differences biological behavior exist type 1 icc perihilar cholangiocarcinoma tumor budding prognostically important icc pathogenetic role biliary tract carcinomas might different anatomic location stn","probabilities":0.9799733,"Title":"Tumor Budding In Intrahepatic Cholangiocarcinoma: A Predictor Of Postsurgery Outcomes","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is an extremely aggressive carcinoma. Useful predictors for the patients' prognosis after surgery have not been fully established. From the University of Tokyo Hospital pathology archives, we reviewed 107 cases of ICC, 54 cases of perihilar cholangiocarcinoma, and 40 cases of extrahepatic cholangiocarcinoma (ECC); we also investigated the significance of tumor budding in ICC, in comparison with perihilar cholangiocarcinoma and ECC. The tumor-budding frequencies were different by tumor location: 40.2% (43/107) in ICC, 70.4% (38/54) in perihilar cholangiocarcinoma, and 60.0% (24/40) in ECC. Tumor budding in ICC was associated with many pathologic indicators associated with invasion, such as major vascular invasion (P=0.012) and Union for International Cancer Control stage (P=0.007). Univariate and multivariate Cox regression analyses revealed tumor budding as a powerful prognostic factor for both recurrence-free survival (RFS) and overall survival (OS) in ICC by univariate (RFS: hazard ratio [HR]: 2.666; 95% confidence interval [CI]: 1.517-4.683, OS: HR: 4.206; 95% CI: 2.447-7.230) and by multivariate analyses (RFS: HR: 3.038; 95% CI: 1.591-5.973, OS: HR: 4.547, 95% CI: 2.348-8.805). Tumor budding was also a significant prognostic factor of perihilar cholangiocarcinoma, but not of ECC. When ICC was divided into 2 subtypes, type 1 (hilar) and type 2 (peripheral), tumor budding was the strong prognostic factor in type 2 ICC, but not in type 1 ICC, suggesting that some differences in biological behavior exist between type 1 ICC and perihilar cholangiocarcinoma. Tumor budding is prognostically important in ICC, and its pathogenetic role in biliary tract carcinomas might be different by anatomic location.","Source":"STN","category":"HUMAN","training_data":"Tumor Budding In Intrahepatic Cholangiocarcinoma: A Predictor Of Postsurgery Outcomes Intrahepatic cholangiocarcinoma (ICC) is an extremely aggressive carcinoma. Useful predictors for the patients' prognosis after surgery have not been fully established. From the University of Tokyo Hospital pathology archives, we reviewed 107 cases of ICC, 54 cases of perihilar cholangiocarcinoma, and 40 cases of extrahepatic cholangiocarcinoma (ECC); we also investigated the significance of tumor budding in ICC, in comparison with perihilar cholangiocarcinoma and ECC. The tumor-budding frequencies were different by tumor location: 40.2% (43/107) in ICC, 70.4% (38/54) in perihilar cholangiocarcinoma, and 60.0% (24/40) in ECC. Tumor budding in ICC was associated with many pathologic indicators associated with invasion, such as major vascular invasion (P=0.012) and Union for International Cancer Control stage (P=0.007). Univariate and multivariate Cox regression analyses revealed tumor budding as a powerful prognostic factor for both recurrence-free survival (RFS) and overall survival (OS) in ICC by univariate (RFS: hazard ratio [HR]: 2.666; 95% confidence interval [CI]: 1.517-4.683, OS: HR: 4.206; 95% CI: 2.447-7.230) and by multivariate analyses (RFS: HR: 3.038; 95% CI: 1.591-5.973, OS: HR: 4.547, 95% CI: 2.348-8.805). Tumor budding was also a significant prognostic factor of perihilar cholangiocarcinoma, but not of ECC. When ICC was divided into 2 subtypes, type 1 (hilar) and type 2 (peripheral), tumor budding was the strong prognostic factor in type 2 ICC, but not in type 1 ICC, suggesting that some differences in biological behavior exist between type 1 ICC and perihilar cholangiocarcinoma. Tumor budding is prognostically important in ICC, and its pathogenetic role in biliary tract carcinomas might be different by anatomic location. STN","prediction_labels":"HUMAN"},{"cleaned":"role erbb family receptor tyrosine kinases cholangiocyte biology erbb family comprises four distinct tyrosine kinase receptors egfr erbb1 her1 erbb2 her2 erbb3 her3 erbb4 her4 trigger intracellular signals origin essential cellular functions including differentiation proliferation survival migration epithelial cells named cholangiocytes line intrahepatic extrahepatic bile ducts contribute substantially biliary secretory functions bile transport although erbb receptors widely studied cholangiocarcinoma cca malignancy biliary tract knowledge receptors biliary epithelium physiology non malignant cholangiopathies far complete current knowledge suggests role epidermal growth factor receptor egfr cholangiocyte specification proliferation hepatocyte transdifferentiation cholangiocytes liver regeneration restore biliary epithelium integrity high expression activation egfr erbb2 recently demonstrated biliary lithiasis primary sclerosing cholangitis two cholangiopathies regarded risk factors cca cca erbb receptors frequently overexpressed leading tumor progression low prognosis anti erbb therapies efficient preclinical trials suggested existence resistance mechanisms need identify predictive factors therapy response review aims compile current knowledge functions erbb receptors physiology physiopathology biliary epithelium hepatology 2018 67 762 773 pubmed","probabilities":0.9799733,"Title":"Role of ErbB/HER family of receptor tyrosine kinases in cholangiocyte biology","Abstract":"The ErbB/HER family comprises four distinct tyrosine kinase receptors, EGFR/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4, which trigger intracellular signals at the origin of essential cellular functions, including differentiation, proliferation, survival, and migration. Epithelial cells, named cholangiocytes, that line intrahepatic and extrahepatic bile ducts, contribute substantially to biliary secretory functions and bile transport. Although ErbB receptors have been widely studied in cholangiocarcinoma (CCA), a malignancy of the biliary tract, knowledge of these receptors in biliary epithelium physiology and in non-malignant cholangiopathies is far from complete. Current knowledge suggests a role for epidermal growth factor receptor (EGFR) in cholangiocyte specification and proliferation, and in hepatocyte transdifferentiation into cholangiocytes during liver regeneration to restore biliary epithelium integrity. High expression and activation of EGFR and/or ErbB2 were recently demonstrated in biliary lithiasis and primary sclerosing cholangitis, two cholangiopathies regarded as risk factors for CCA. In CCA, ErbB receptors are frequently overexpressed, leading to tumor progression and low prognosis. Anti-ErbB therapies were efficient only in preclinical trials and have suggested the existence of resistance mechanisms with the need to identify predictive factors of therapy response. This review aims to compile the current knowledge on the functions of ErbB receptors in physiology and physiopathology of the biliary epithelium. (Hepatology 2018;67:762-773).","Source":"PubMed","category":"HUMAN","training_data":"Role of ErbB/HER family of receptor tyrosine kinases in cholangiocyte biology The ErbB/HER family comprises four distinct tyrosine kinase receptors, EGFR/ErbB1/HER1, ErbB2/HER2, ErbB3/HER3, and ErbB4/HER4, which trigger intracellular signals at the origin of essential cellular functions, including differentiation, proliferation, survival, and migration. Epithelial cells, named cholangiocytes, that line intrahepatic and extrahepatic bile ducts, contribute substantially to biliary secretory functions and bile transport. Although ErbB receptors have been widely studied in cholangiocarcinoma (CCA), a malignancy of the biliary tract, knowledge of these receptors in biliary epithelium physiology and in non-malignant cholangiopathies is far from complete. Current knowledge suggests a role for epidermal growth factor receptor (EGFR) in cholangiocyte specification and proliferation, and in hepatocyte transdifferentiation into cholangiocytes during liver regeneration to restore biliary epithelium integrity. High expression and activation of EGFR and/or ErbB2 were recently demonstrated in biliary lithiasis and primary sclerosing cholangitis, two cholangiopathies regarded as risk factors for CCA. In CCA, ErbB receptors are frequently overexpressed, leading to tumor progression and low prognosis. Anti-ErbB therapies were efficient only in preclinical trials and have suggested the existence of resistance mechanisms with the need to identify predictive factors of therapy response. This review aims to compile the current knowledge on the functions of ErbB receptors in physiology and physiopathology of the biliary epithelium. (Hepatology 2018;67:762-773). PubMed","prediction_labels":"HUMAN"},{"cleaned":"id3 promotes stem cell features predicts chemotherapeutic response intrahepatic cholangiocarcinoma cancer stem cells contribute high rate recurrence chemotherapeutic resistance many types cancer including intrahepatic cholangiocarcinoma icc inhibitor differentiation 3 id3 reported promote cancer stem cells role icc obscure study identified id3 highly expressed human icc tissues compared matched normal tissues correlates poor prognosis functional studies demonstrate id3 required stemness maintenance cholangiocarcinoma vitro vivo consistent regulation cancer stem cell features id3 transgenic expression id3 enhances chemoresistance cholangiocarcinoma cells moreover found icc patients low id3 levels benefited postoperative transarterial chemoembolization whereas patients high id3 levels indicating significance id3 individualized icc therapy mechanistically id3 interact e47 block e47 recruitment promoter catenin leads activation wnt catenin signaling conclusion results show id3 promote stemness icc increasing transcriptional activity catenin serve biomarker predicting icc patients response adjuvant chemotherapeutics stn","probabilities":0.9467213,"Title":"Id3 Promotes Stem Cell Features And Predicts Chemotherapeutic Response Of Intrahepatic Cholangiocarcinoma","Abstract":"Cancer stem cells contribute to a high rate of recurrence and chemotherapeutic resistance in many types of cancer, including intrahepatic cholangiocarcinoma (ICC). Inhibitor of differentiation 3 (ID3) has been reported to promote cancer stem cells, but its role in ICC is obscure. In this study, we identified that ID3 is highly expressed in human ICC tissues compared with matched normal tissues and correlates with poor prognosis. Functional studies demonstrate that ID3 is required for stemness maintenance in cholangiocarcinoma both in vitro and in vivo. Consistent with the regulation of cancer stem cell features by ID3, transgenic expression of ID3 enhances chemoresistance of cholangiocarcinoma cells. Moreover, we found that ICC patients with low ID3 levels benefited from postoperative transarterial chemoembolization, whereas patients with high ID3 levels did not, indicating the significance of ID3 in individualized ICC therapy. Mechanistically, ID3 could interact with E47 and block E47 recruitment to the promoter of β-catenin, which leads to activation of Wnt/β-catenin signaling. Conclusion: Our results show that ID3 could promote the stemness of ICC by increasing the transcriptional activity of β-catenin and could serve as a biomarker in predicting ICC patients' response to adjuvant chemotherapeutics.","Source":"STN","category":"ANIMAL","training_data":"Id3 Promotes Stem Cell Features And Predicts Chemotherapeutic Response Of Intrahepatic Cholangiocarcinoma Cancer stem cells contribute to a high rate of recurrence and chemotherapeutic resistance in many types of cancer, including intrahepatic cholangiocarcinoma (ICC). Inhibitor of differentiation 3 (ID3) has been reported to promote cancer stem cells, but its role in ICC is obscure. In this study, we identified that ID3 is highly expressed in human ICC tissues compared with matched normal tissues and correlates with poor prognosis. Functional studies demonstrate that ID3 is required for stemness maintenance in cholangiocarcinoma both in vitro and in vivo. Consistent with the regulation of cancer stem cell features by ID3, transgenic expression of ID3 enhances chemoresistance of cholangiocarcinoma cells. Moreover, we found that ICC patients with low ID3 levels benefited from postoperative transarterial chemoembolization, whereas patients with high ID3 levels did not, indicating the significance of ID3 in individualized ICC therapy. Mechanistically, ID3 could interact with E47 and block E47 recruitment to the promoter of β-catenin, which leads to activation of Wnt/β-catenin signaling. Conclusion: Our results show that ID3 could promote the stemness of ICC by increasing the transcriptional activity of β-catenin and could serve as a biomarker in predicting ICC patients' response to adjuvant chemotherapeutics. STN","prediction_labels":"ANIMAL"},{"cleaned":"chemotherapy inoperable advanced metastatic cholangiocarcinoma retrospective analysis 78 cases single center four years background systemic chemotherapy treatment choice inoperable advanced metastatic cholangiocarcinoma according phase ii iii trials regimens combining 5 fluorouracil 5fu gemcitabine platinum salt provided overall response rate 12 50 median overall survival 5 16 months methods retrospective analysis 78 consecutive cases inoperable cholangiocarcinoma treated palliative chemotherapy july 2005 november 2009 one center firstly aimed evaluate impact palliative chemotherapy terms survival secondly analyze possible related prognostic factors results cohort included 25 female 53 male patients mean age 60 8 11 4 years intrahepatic extrahepatic cholangiocarcinoma observed 57 21 patients respectively first line chemotherapy regimens follows gemcitabine n 7 gemcitabine plus oxaliplatin without cetuximab n 62 5fu plus cisplatin n 9 none patients achieved complete response partial response rate 35 9 27 78 stable disease rate 26 9 21 78 giving disease control rate 62 8 time analysis median follow 18 months 13 patients survivors median overall survival 10 months 95 confidence interval ci 7 12 median progression free survival 7 months 95 ci 6 8 upon univariate analysis distribution disease significantly linked prognosis median overall survival 10 months 95 ci 10 24 solitary tumors versus 7 months 95 ci 6 11 case infiltrative multifocal tumors p 0 039 conclusion disease control rate overall survival progression free survival single center retrospective study agreement earlier reports specific features cohort large proportion cholangiocarcinoma associated cirrhosis n 30 78 38 5 mostly intrahepatic n 25 30 83 5 confirms increasing incidence intrahepatic localization epidemiological link recently reported intrahepatic biliary tract carcinoma cirrhosis pubmed","probabilities":0.9799733,"Title":"Chemotherapy for inoperable advanced or metastatic cholangiocarcinoma: retrospective analysis of 78 cases in a single center over four years","Abstract":"BACKGROUND: Systemic chemotherapy is the treatment of choice for inoperable (advanced or metastatic) cholangiocarcinoma. According to phase II and III trials, regimens combining 5-fluorouracil (5FU) or gemcitabine with a platinum salt have provided an overall response rate of 12-50% with a median overall survival of 5-16 months. METHODS: This was a retrospective analysis of 78 consecutive cases of inoperable cholangiocarcinoma treated by palliative chemotherapy from July 2005 to November 2009 in one center. We firstly aimed to evaluate the impact of palliative chemotherapy in terms of survival and secondly to analyze possible related prognostic factors. RESULTS: This cohort included 25 female and 53 male patients, with a mean age of 60.8 ± 11.4 years. Intrahepatic and extrahepatic cholangiocarcinoma were observed in 57 and 21 patients, respectively. First-line chemotherapy regimens were as follows: gemcitabine (n = 7), gemcitabine plus oxaliplatin (with or without cetuximab; n = 62) and 5FU plus cisplatin (n = 9). None of the patients achieved a complete response. The partial response rate was 35.9% (27/78), and the stable disease rate was 26.9% (21/78), giving a disease control rate of 62.8%. At the time of this analysis, with a median follow-up of 18 months, 13 patients were survivors. Median overall survival was 10 months [95% confidence interval (CI) 7-12], and median progression-free survival was 7 months (95% CI 6-8). Upon univariate analysis, only the distribution of the disease was significantly linked with prognosis, with a median overall survival of 10 months (95% CI 10-24) for solitary tumors versus 7 months (95% CI 6-11) in the case of infiltrative or multifocal tumors (p = 0.039). CONCLUSION: The disease control rate, overall survival and progression free-survival in this single-center retrospective study were in agreement with earlier reports. Specific features of this cohort were a large proportion of cholangiocarcinoma with associated cirrhosis (n = 30/78, 38.5%), mostly intrahepatic (n = 25/30, 83.5%). This confirms the increasing incidence of intrahepatic localization and the epidemiological link recently reported between intrahepatic biliary tract carcinoma and cirrhosis.","Source":"PubMed","category":"HUMAN","training_data":"Chemotherapy for inoperable advanced or metastatic cholangiocarcinoma: retrospective analysis of 78 cases in a single center over four years BACKGROUND: Systemic chemotherapy is the treatment of choice for inoperable (advanced or metastatic) cholangiocarcinoma. According to phase II and III trials, regimens combining 5-fluorouracil (5FU) or gemcitabine with a platinum salt have provided an overall response rate of 12-50% with a median overall survival of 5-16 months. METHODS: This was a retrospective analysis of 78 consecutive cases of inoperable cholangiocarcinoma treated by palliative chemotherapy from July 2005 to November 2009 in one center. We firstly aimed to evaluate the impact of palliative chemotherapy in terms of survival and secondly to analyze possible related prognostic factors. RESULTS: This cohort included 25 female and 53 male patients, with a mean age of 60.8 ± 11.4 years. Intrahepatic and extrahepatic cholangiocarcinoma were observed in 57 and 21 patients, respectively. First-line chemotherapy regimens were as follows: gemcitabine (n = 7), gemcitabine plus oxaliplatin (with or without cetuximab; n = 62) and 5FU plus cisplatin (n = 9). None of the patients achieved a complete response. The partial response rate was 35.9% (27/78), and the stable disease rate was 26.9% (21/78), giving a disease control rate of 62.8%. At the time of this analysis, with a median follow-up of 18 months, 13 patients were survivors. Median overall survival was 10 months [95% confidence interval (CI) 7-12], and median progression-free survival was 7 months (95% CI 6-8). Upon univariate analysis, only the distribution of the disease was significantly linked with prognosis, with a median overall survival of 10 months (95% CI 10-24) for solitary tumors versus 7 months (95% CI 6-11) in the case of infiltrative or multifocal tumors (p = 0.039). CONCLUSION: The disease control rate, overall survival and progression free-survival in this single-center retrospective study were in agreement with earlier reports. Specific features of this cohort were a large proportion of cholangiocarcinoma with associated cirrhosis (n = 30/78, 38.5%), mostly intrahepatic (n = 25/30, 83.5%). This confirms the increasing incidence of intrahepatic localization and the epidemiological link recently reported between intrahepatic biliary tract carcinoma and cirrhosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival outcomes primary sclerosing cholangitis patients inflammatory bowel disease liver transplantation introduction impact ammatory bowel disease ibd patient outcomes liver transplantation lt primary sclerosing cholangitis psc largely unknown concurrent ibd exists 60 70 patients psc may associated greater risk graft failure retransplantation led debate validity prophylactic pre transplant colectomies furthermore de novo ibd lt associated higher rates retransplantation however evidence pertaining impact patient survival outcomes lacking aimed evaluate survival outcomes patients without ibd transplanted psc well patients underwent pre transplant colectomies de novo ibd methods electronic medical records 1172 lt patients retrospec tively reviewed identify underwent rst lt psc 1 january 1992 31 april 2018 two tertiary transplant centers pa tients ibd strati ed preexisting de novo cohorts accord ing date diagnosis relative lt patients ibd underwent colectomy transplant classi ed non ibd mortal ity data including date cause death collected patients kaplan meier survival analysis log rank tests performed results total 110 patients underwent lt psc median follow duration 8 years iqr 3 14 mean recipient age 45 14 years 57 male seventy patients 63 ibd 63 90 ulcerative colitis uc four 6 crohn disease three 4 indeterminate colitis sixty patients diagnosis ibd transplantation 15 25 underwent colectomy fore transplant 12 ibd three bowel cancer 12 20 underwent colectomy transplant ve uc seven bowel cancer underlying ibd ten patients developed de novo ibd follow period twenty one patients 19 died median time death 12 years iqr 1 16 years sepsis commonest cause death 25 followed recurrent psc three patients 13 cholangiocarcinoma three patients 13 estimated psc patient survival probabilities without ibd 98 versus 92 5 years p 0 1 98 versus 87 p 0 01 10 years however conclusion follow period signi cant differ ence groups 80 vs 82 p 0 75 de novo ibd associated reduced patient survival time point p 0 39 bi variate analysis revealed pre transplant colectomy signi cant predictor mortality 10 years odds ratio 16 1 p 0 003 however overall mortality signi cantly different groups p 0 42 conclusion survival outcomes patients underwent liver trans plantation psc high cohort irrespective whether coexistent ibd although survival rates signi cantly higher 10 years patients ibd overall survival beyond 10 years psc ibd psc non ibd transplant patients similar de novo ibd con ferred additional risk mortality survival bene pre transplant colectomies patients ibd google scholar","probabilities":0.9799733,"Title":"Survival Outcomes Of Primary Sclerosing Cholangitis Patients With Inflammatory Bowel Disease After Liver Transplantation","Abstract":"Introduction: The impact of inflammatory bowel disease (IBD) on patient\noutcomes after liver transplantation (LT) for primary sclerosing cholangitis\n(PSC) is largely unknown. Concurrent IBD exists in 60–70% of patients\nwith PSC and may be associated with greater risk of graft failure and\nretransplantation, which has led to debate about the validity of prophylactic\npre-transplant colectomies. Furthermore, de novo IBD after LT has been\nassociated with higher rates of retransplantation; however, evidence\npertaining to its impact on patient survival outcomes is lacking. We aimed\nto evaluate the survival outcomes of patients with and without IBD who\nwere transplanted for PSC, as well as patients who underwent pre-\ntransplant colectomies or had de novo IBD.\nMethods: Electronic medical records of 1172 LT patients were retrospec-\ntively reviewed to identify those who underwent first LT for PSC between\n1 January 1992 and 31 April 2018 at two tertiary transplant centers. Pa-\ntients with IBD were stratified into preexisting and de novo cohorts accord-\ning to their date of diagnosis relative to LT. Patients with IBD who\nunderwent colectomy before transplant were classified as non-IBD. Mortal-\nity data, including date and cause of death, were collected for all patients.\nKaplan–Meier survival analysis and log-rank tests were performed.\nResults: A total of 110 patients underwent LT for PSC, with median\nfollow-up duration of 8 years (IQR, 3–14). Mean recipient age was\n45 ± 14 years; 57% were male. Seventy patients (63%) had IBD, of whom\n63 (90%) had ulcerative colitis (UC), four (6%) had Crohn’s disease, and\nthree (4%) had indeterminate colitis. Sixty patients had a diagnosis of\nIBD before transplantation, of whom 15 (25%) underwent a colectomy be-\nfore transplant (12 for IBD, three for bowel cancer), and 12 (20%)\nunderwent colectomy after transplant (five for UC, seven for bowel cancer\nand underlying IBD). Ten patients developed de novo IBD during the\nfollow-up period. Twenty-one patients (19%) died, with a median time to\ndeath of 12 years (IQR, 1–16 years). Sepsis was the commonest cause of\ndeath (25%), followed by recurrent PSC in three patients (13%) and cholangiocarcinoma in three patients (13%). The estimated PSC patient\nsurvival probabilities with and without IBD were 98% versus 92% at\n5 years (P = 0.1) and 98% versus 87% (P = 0.01) at 10 years. However,\nat the conclusion of the follow-up period, there was no significant differ-\nence between the groups (80% vs 82%; P = 0.75) De novo IBD was not\nassociated with reduced patient survival at any time point (P = 0.39). Bi-\nvariate analysis revealed that pre-transplant colectomy was a significant\npredictor of mortality at 10 years (odds ratio, 16.1; P = 0.003); however,\noverall mortality was not significantly different between the groups\n(P = 0.42).\nConclusion: Survival outcomes for patients who underwent liver trans-\nplantation for PSC were high in our cohort, irrespective of whether there\nwas coexistent IBD. Although survival rates were significantly higher at\n10 years in patients with IBD, overall survival beyond 10 years in PSC-\nIBD and PSC non-IBD transplant patients was similar. De novo IBD con-\nferred no additional risk of mortality. There was no survival benefit from\npre-transplant colectomies in patients with IBD","Source":"Google Scholar","category":"HUMAN","training_data":"Survival Outcomes Of Primary Sclerosing Cholangitis Patients With Inflammatory Bowel Disease After Liver Transplantation Introduction: The impact of inflammatory bowel disease (IBD) on patient\noutcomes after liver transplantation (LT) for primary sclerosing cholangitis\n(PSC) is largely unknown. Concurrent IBD exists in 60–70% of patients\nwith PSC and may be associated with greater risk of graft failure and\nretransplantation, which has led to debate about the validity of prophylactic\npre-transplant colectomies. Furthermore, de novo IBD after LT has been\nassociated with higher rates of retransplantation; however, evidence\npertaining to its impact on patient survival outcomes is lacking. We aimed\nto evaluate the survival outcomes of patients with and without IBD who\nwere transplanted for PSC, as well as patients who underwent pre-\ntransplant colectomies or had de novo IBD.\nMethods: Electronic medical records of 1172 LT patients were retrospec-\ntively reviewed to identify those who underwent first LT for PSC between\n1 January 1992 and 31 April 2018 at two tertiary transplant centers. Pa-\ntients with IBD were stratified into preexisting and de novo cohorts accord-\ning to their date of diagnosis relative to LT. Patients with IBD who\nunderwent colectomy before transplant were classified as non-IBD. Mortal-\nity data, including date and cause of death, were collected for all patients.\nKaplan–Meier survival analysis and log-rank tests were performed.\nResults: A total of 110 patients underwent LT for PSC, with median\nfollow-up duration of 8 years (IQR, 3–14). Mean recipient age was\n45 ± 14 years; 57% were male. Seventy patients (63%) had IBD, of whom\n63 (90%) had ulcerative colitis (UC), four (6%) had Crohn’s disease, and\nthree (4%) had indeterminate colitis. Sixty patients had a diagnosis of\nIBD before transplantation, of whom 15 (25%) underwent a colectomy be-\nfore transplant (12 for IBD, three for bowel cancer), and 12 (20%)\nunderwent colectomy after transplant (five for UC, seven for bowel cancer\nand underlying IBD). Ten patients developed de novo IBD during the\nfollow-up period. Twenty-one patients (19%) died, with a median time to\ndeath of 12 years (IQR, 1–16 years). Sepsis was the commonest cause of\ndeath (25%), followed by recurrent PSC in three patients (13%) and cholangiocarcinoma in three patients (13%). The estimated PSC patient\nsurvival probabilities with and without IBD were 98% versus 92% at\n5 years (P = 0.1) and 98% versus 87% (P = 0.01) at 10 years. However,\nat the conclusion of the follow-up period, there was no significant differ-\nence between the groups (80% vs 82%; P = 0.75) De novo IBD was not\nassociated with reduced patient survival at any time point (P = 0.39). Bi-\nvariate analysis revealed that pre-transplant colectomy was a significant\npredictor of mortality at 10 years (odds ratio, 16.1; P = 0.003); however,\noverall mortality was not significantly different between the groups\n(P = 0.42).\nConclusion: Survival outcomes for patients who underwent liver trans-\nplantation for PSC were high in our cohort, irrespective of whether there\nwas coexistent IBD. Although survival rates were significantly higher at\n10 years in patients with IBD, overall survival beyond 10 years in PSC-\nIBD and PSC non-IBD transplant patients was similar. De novo IBD con-\nferred no additional risk of mortality. There was no survival benefit from\npre-transplant colectomies in patients with IBD Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"expression analysis akt mtor signaling pathway primary tumors cell lines derived gallbladder cancer background gallbladder carcinoma gbc highly fatal disease poor prognosis mammalian target rapamycin mtor serine threonine kinase plays central role cell growth homeostasis regulation frequently altered various tumors attractive target cancer therapy however status gbc remains unclear objectives analyze expression mtor signaling pathway primary tumors cell lines derived gallbladder cancer evaluate vitro effect mtor inhibitors cell viability migration design expression five components akt mtor signaling pathway phospho mtor total protein mtor akt 4ebp1 p70s6k eif4e examined immunohistochemistry tissue microarrays tmas containing 128 advanced gbc 99 cases chronic cholecystitis cc association phospho mtor expression clinical variables evaluated also examined activation akt mtor pathway based phospho akt phospho p70s6k phospho 4ebp1 phospho eif4e expression eight gbc cell lines western blot finally effect four mtor inhibitors ly294002 rapamycin everolimus azd8055 cell viability vitro migration assessed mts transwell chamber assays statistical analysis performed using significance level p 0 05 results observed significant ihc overexpression akt mtor pathway component primary tumor samples compared cc survival analysis indicated gbc patients whose tumors overexpressed phosphomtor poorer prognosis p 0 02 tgbc2 tkb cell line showed constitutive activation akt mtor pathway western blot assay treatment different mtor inhibitors significantly reduced viability migration capacity p 0 05 conclusions akt mtor signaling pathway abnormally expressed gbc suggest mtor potential therapeutic target treatment advanced gbc addition phospho mtor ihc expression characterizes subset gbc cancers might optimally benefit anti mtor therapies fondecyt project 1090171 diufro project di11 0039 google scholar","probabilities":0.9467213,"Title":"Expression Analysis Of Akt/Mtor Signaling Pathway In Primary Tumors And Cell Lines Derived From Gallbladder Cancer","Abstract":"Background: Gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear. Objectives: To analyze the expression of mTOR signaling pathway in primary tumors and cell lines derived from gallbladder cancer and to evaluate the in vitro effect of mTOR inhibitors on cell viability and migration. Design: The expression of five components of AKT/mTOR signaling pathway (phospho- mTOR and total protein of mTOR, AKT, 4EBP1, P70S6K and eIF4e) was examined by immunohistochemistry in tissue microarrays (TMAs) containing 128 advanced GBC and 99 cases of chronic cholecystitis (CC). Association between phospho-mTOR expression and clinical variables was evaluated. We also examined the activation of the AKT/mTOR pathway based on phospho-AKT, phospho-p70S6K, phospho-4EBP1 and phospho-eIF4E expression in eight GBC cell lines by Western blot. Finally, the effect of four mTOR inhibitors (LY294002, Rapamycin, Everolimus and AZD8055) on cell viability and in vitro migration was assessed by MTS and Transwell chamber assays. Statistical analysis was performed using a significance level P < 0.05. Results: We observed a significant IHC overexpression of AKT-mTor pathway component in primary tumor samples, compared to CC. Survival analysis indicated that GBC patients whose tumors overexpressed phosphomTOR had a poorer prognosis (P = 0.02). TGBC2-TKB cell line showed a constitutive activation of the AKT/mTOR pathway (Western Blot Assay) and the treatment with different mTOR inhibitors significantly reduced its viability and migration capacity (p <0.05). Conclusions: The AKT/mTOR signaling pathway is abnormally expressed in GBC which suggest that mTOR could be a potential therapeutic target for the treatment of advanced GBC. In addition, phospho-mTOR IHC expression characterizes a subset of GBC cancers that might optimally benefit with anti-mTOR therapies. FONDECYT Project 1090171 and DIUFRO project DI11-0039.","Source":"Google Scholar","category":"ANIMAL","training_data":"Expression Analysis Of Akt/Mtor Signaling Pathway In Primary Tumors And Cell Lines Derived From Gallbladder Cancer Background: Gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear. Objectives: To analyze the expression of mTOR signaling pathway in primary tumors and cell lines derived from gallbladder cancer and to evaluate the in vitro effect of mTOR inhibitors on cell viability and migration. Design: The expression of five components of AKT/mTOR signaling pathway (phospho- mTOR and total protein of mTOR, AKT, 4EBP1, P70S6K and eIF4e) was examined by immunohistochemistry in tissue microarrays (TMAs) containing 128 advanced GBC and 99 cases of chronic cholecystitis (CC). Association between phospho-mTOR expression and clinical variables was evaluated. We also examined the activation of the AKT/mTOR pathway based on phospho-AKT, phospho-p70S6K, phospho-4EBP1 and phospho-eIF4E expression in eight GBC cell lines by Western blot. Finally, the effect of four mTOR inhibitors (LY294002, Rapamycin, Everolimus and AZD8055) on cell viability and in vitro migration was assessed by MTS and Transwell chamber assays. Statistical analysis was performed using a significance level P < 0.05. Results: We observed a significant IHC overexpression of AKT-mTor pathway component in primary tumor samples, compared to CC. Survival analysis indicated that GBC patients whose tumors overexpressed phosphomTOR had a poorer prognosis (P = 0.02). TGBC2-TKB cell line showed a constitutive activation of the AKT/mTOR pathway (Western Blot Assay) and the treatment with different mTOR inhibitors significantly reduced its viability and migration capacity (p <0.05). Conclusions: The AKT/mTOR signaling pathway is abnormally expressed in GBC which suggest that mTOR could be a potential therapeutic target for the treatment of advanced GBC. In addition, phospho-mTOR IHC expression characterizes a subset of GBC cancers that might optimally benefit with anti-mTOR therapies. FONDECYT Project 1090171 and DIUFRO project DI11-0039. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"characterization intrahepatic cholangiocarcinoma curative resection outcome prognostic factor recurrence background intrahepatic cholangiocarcinoma icc relatively rare subtype cholangiocarcinoma study herein gathered experience surgical treatment icc aimed analyze prognosis patients received curative intent liver resection methods total 216 patients undergone curative intent liver resection icc january 1977 december 2014 retrospectively reviewed results overall rates 5 years recurrence free survival rfs overall survival os 26 1 33 9 respectively based multivariate analysis four independent adverse prognostic factors including morphology patterns maximum tumor size 5 cm pathological lymph node involvement vascular invasion identified affecting rfs curative intent liver resection icc among patients cholangiocarcinoma recurrence 27 16 9 able receive surgical resection recurrent cholangiocarcinoma significantly better outcome remaining patients conclusion despite curative resection general outcome patients icc still unsatisfactory high incidence cholangiocarcinoma recurrence operation tumor factors associated cholangiocarcinoma remain crucial prognosis patients icc curative liver resection moreover aggressive attitude toward repeat resection postoperative recurrent cholangiocarcinoma provide favorable outcome patients pubmed","probabilities":0.9799733,"Title":"Characterization of intrahepatic cholangiocarcinoma after curative resection: outcome, prognostic factor, and recurrence","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare subtype of cholangiocarcinoma. The study herein gathered experience of surgical treatment for ICC, and aimed to analyze the prognosis of patients who had received curative-intent liver resection. METHODS: A total of 216 patients who had undergone curative-intent liver resection for ICC between January 1977 and December 2014 was retrospectively reviewed. RESULTS: Overall, the rates of 5-years recurrence-free survival (RFS) and overall survival (OS) were 26.1 and 33.9% respectively. Based on multivariate analysis, four independent adverse prognostic factors including morphology patterns, maximum tumor size > 5 cm, pathological lymph node involvement, and vascular invasion were identified as affecting RFS after curative-intent liver resection for ICC. Among patients with cholangiocarcinoma recurrence, only 27 (16.9%) were able to receive surgical resection for recurrent cholangiocarcinoma that had a significantly better outcome than the remaining patients. CONCLUSION: Despite curative resection, the general outcome of patients with ICC is still unsatisfactory because of a high incidence of cholangiocarcinoma recurrence after operation. Tumor factors associated with cholangiocarcinoma remain crucial for the prognosis of patients with ICC after curative liver resection. Moreover, aggressive attitude toward repeat resection for the postoperative recurrent cholangiocarcinoma could provide a favorable outcome for patients.","Source":"PubMed","category":"HUMAN","training_data":"Characterization of intrahepatic cholangiocarcinoma after curative resection: outcome, prognostic factor, and recurrence BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a relatively rare subtype of cholangiocarcinoma. The study herein gathered experience of surgical treatment for ICC, and aimed to analyze the prognosis of patients who had received curative-intent liver resection. METHODS: A total of 216 patients who had undergone curative-intent liver resection for ICC between January 1977 and December 2014 was retrospectively reviewed. RESULTS: Overall, the rates of 5-years recurrence-free survival (RFS) and overall survival (OS) were 26.1 and 33.9% respectively. Based on multivariate analysis, four independent adverse prognostic factors including morphology patterns, maximum tumor size > 5 cm, pathological lymph node involvement, and vascular invasion were identified as affecting RFS after curative-intent liver resection for ICC. Among patients with cholangiocarcinoma recurrence, only 27 (16.9%) were able to receive surgical resection for recurrent cholangiocarcinoma that had a significantly better outcome than the remaining patients. CONCLUSION: Despite curative resection, the general outcome of patients with ICC is still unsatisfactory because of a high incidence of cholangiocarcinoma recurrence after operation. Tumor factors associated with cholangiocarcinoma remain crucial for the prognosis of patients with ICC after curative liver resection. Moreover, aggressive attitude toward repeat resection for the postoperative recurrent cholangiocarcinoma could provide a favorable outcome for patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"idh1 frequently mutated gene potential effect exosomes releasement epigenetically regulating p2rx7 intrahepatic cholangiocarcinoma biliary tract cancers btcs heterogeneous characterized late diagnosis fatal outcome identify new biomarkers btcs performed robust rank aggreg rra analysis identified idh1 mutation common icc idh1r132c frequent type moreover identified p2rx7 45 genes downregulated genes hypermethylation idh1r132c mutated cells wgcna results predicted p2rx7 influence cholangiocarcinoma exosomes related manners finally confirmed p2rx7 downregulated idh1r132c mutated cells well expression cd9 cd81 experiments conclusion idh1r132c mutation relatively prevalent icc p2rx7 might potential downstream gene might related exosomes releasement stn","probabilities":0.9799733,"Title":"Idh1 As A Frequently Mutated Gene Has Potential Effect On Exosomes Releasement By Epigenetically Regulating P2Rx7 In Intrahepatic Cholangiocarcinoma","Abstract":"Biliary tract cancers (BTCs) was heterogeneous and characterized by late diagnosis and fatal outcome. To identify new biomarkers for BTCs, we performed Robust Rank Aggreg (RRA) analysis and identified that IDH1 mutation was common in ICC, while IDH1R132C was the most frequent type. Moreover, we identified P2RX7 and other 45 genes as downregulated genes with hypermethylation in IDH1R132C mutated cells. The WGCNA results predicted that P2RX7 could influence cholangiocarcinoma by exosomes related manners. Finally, we confirmed that P2RX7 was downregulated in IDH1R132C mutated cells as well as the expression of CD9 and CD81 by experiments. In conclusion, IDH1R132C mutation was relatively prevalent in ICC. P2RX7 might be a potential downstream gene and it might be related to exosomes releasement.","Source":"STN","category":"ANIMAL","training_data":"Idh1 As A Frequently Mutated Gene Has Potential Effect On Exosomes Releasement By Epigenetically Regulating P2Rx7 In Intrahepatic Cholangiocarcinoma Biliary tract cancers (BTCs) was heterogeneous and characterized by late diagnosis and fatal outcome. To identify new biomarkers for BTCs, we performed Robust Rank Aggreg (RRA) analysis and identified that IDH1 mutation was common in ICC, while IDH1R132C was the most frequent type. Moreover, we identified P2RX7 and other 45 genes as downregulated genes with hypermethylation in IDH1R132C mutated cells. The WGCNA results predicted that P2RX7 could influence cholangiocarcinoma by exosomes related manners. Finally, we confirmed that P2RX7 was downregulated in IDH1R132C mutated cells as well as the expression of CD9 and CD81 by experiments. In conclusion, IDH1R132C mutation was relatively prevalent in ICC. P2RX7 might be a potential downstream gene and it might be related to exosomes releasement. STN","prediction_labels":"HUMAN"},{"cleaned":"comparison laparoscopic open radical cholecystectomy t1b t2 gallbladder cancer purpose gallbladder cancer common malignancy biliary tract laparoscopic open radical surgery including liver resection regional lymphadenectomy applied early gallbladder cancers patients t1b t2 cancers discovered incidentally cholecystectomy specimens present experience managing gallbladder cancer using laparoscopic open surgical approach t1b t2 stage method collected 54 patients t1b t2 stage underwent laparoscopic open radical cholecystectomy mar 2002 dec 2017 divided two groups laparoscopic group 43 open group 11 aim study see complication two groups result total 54 cases included study 43 cases laparoscopic group 11 cases open group age also asa score 3 higher laparoscopic open radical cholecystectomy considering operative time ebl takes longer much bleeding laparoscopic group hospital stay days needed open group among complications mortality cases open radical cholecystectomy group laparoscopic group conclusion laparoscopic approach t1a t2 early gallbladder cancer resulted less complication mortality compared open radical cholecystectomy believed laparoscopic approach may feasible safe selected patients google scholar","probabilities":0.9799733,"Title":"The Comparison Between Laparoscopic And Open Radical Cholecystectomy At T1B & T2 Gallbladder Cancer","Abstract":"Purpose: Gallbladder cancer is the most common malignancy of the biliary tract. Laparoscopic and open radical surgery (including liver resection and regional lymphadenectomy) are applied for some early gallbladder cancers. For patients with T1b & T2 cancers discovered incidentally on cholecystectomy specimens, we present our experience managing gallbladder cancer by using laparoscopic and open surgical approach for T1b & T2 Stage.\nMethod: We collected the 54 patients with T1b & T2 stage who underwent laparoscopic and open radical cholecystectomy from Mar. 2002 to Dec. 2017. We divided them into two groups, the Laparoscopic group (43) and open group (11). The aim of the study was to see any complication between the two groups.\nResult: A total of 54 cases were included in this study. 43 cases were the Laparoscopic group and 11 cases were open group . The age and also ASA score > 3 were higher in laparoscopic than open radical cholecystectomy. Considering operative time & EBL, it takes longer and much more bleeding than laparoscopic group and hospital stay days were needed more in the open group. Among the complications and mortality, there were more cases at open radical cholecystectomy group than laparoscopic group.\nConclusion: Laparoscopic approach for T1a & T2 early gallbladder cancer resulted in less complication & mortality compared with open radical cholecystectomy. We believed that Laparoscopic approach may be feasible and safe for selected patients.","Source":"Google Scholar","category":"HUMAN","training_data":"The Comparison Between Laparoscopic And Open Radical Cholecystectomy At T1B & T2 Gallbladder Cancer Purpose: Gallbladder cancer is the most common malignancy of the biliary tract. Laparoscopic and open radical surgery (including liver resection and regional lymphadenectomy) are applied for some early gallbladder cancers. For patients with T1b & T2 cancers discovered incidentally on cholecystectomy specimens, we present our experience managing gallbladder cancer by using laparoscopic and open surgical approach for T1b & T2 Stage.\nMethod: We collected the 54 patients with T1b & T2 stage who underwent laparoscopic and open radical cholecystectomy from Mar. 2002 to Dec. 2017. We divided them into two groups, the Laparoscopic group (43) and open group (11). The aim of the study was to see any complication between the two groups.\nResult: A total of 54 cases were included in this study. 43 cases were the Laparoscopic group and 11 cases were open group . The age and also ASA score > 3 were higher in laparoscopic than open radical cholecystectomy. Considering operative time & EBL, it takes longer and much more bleeding than laparoscopic group and hospital stay days were needed more in the open group. Among the complications and mortality, there were more cases at open radical cholecystectomy group than laparoscopic group.\nConclusion: Laparoscopic approach for T1a & T2 early gallbladder cancer resulted in less complication & mortality compared with open radical cholecystectomy. We believed that Laparoscopic approach may be feasible and safe for selected patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"imaging spectrum cholangiocarcinoma role diagnosis staging posttreatment evaluation cholangiocarcinoma tumor biliary epithelium increasing incidence imaging appearance behavior treatment cholangiocarcinoma differ according location morphology cholangiocarcinoma usually classified intrahepatic perihilar distal three morphologies mass forming periductal sclerosing intraductal growing surgical resection cure prompt diagnosis accurate staging crucial staging vascular involvement longitudinal spread lymphadenopathy important assess role liver transplantation unresectable peripheral cholangiocarcinoma discussed locoregional therapy extend survival unresectable intrahepatic tumors main risk factors predisposing cholangiocarcinoma parasitic infections primary sclerosing cholangitis choledochal cysts viral hepatitis several inflammatory conditions mimic cholangiocarcinoma including igg4 disease sclerosing cholangitis mirizzi syndrome recurrent pyogenic cholangitis role pet diagnosis staging also discussed radiologists play crucial role diagnosis staging treatment disease pubmed","probabilities":0.9799733,"Title":"Imaging spectrum of cholangiocarcinoma: role in diagnosis, staging, and posttreatment evaluation","Abstract":"Cholangiocarcinoma, a tumor of biliary epithelium, is increasing in incidence. The imaging appearance, behavior, and treatment of cholangiocarcinoma differ according to its location and morphology. Cholangiocarcinoma is usually classified as intrahepatic, perihilar, or distal. The three morphologies are mass-forming, periductal sclerosing, and intraductal growing. As surgical resection is the only cure, prompt diagnosis and accurate staging is crucial. In staging, vascular involvement, longitudinal spread, and lymphadenopathy are important to assess. The role of liver transplantation for unresectable peripheral cholangiocarcinoma will be discussed. Locoregional therapy can extend survival for those with unresectable intrahepatic tumors. The main risk factors predisposing to cholangiocarcinoma are parasitic infections, primary sclerosing cholangitis, choledochal cysts, and viral hepatitis. Several inflammatory conditions can mimic cholangiocarcinoma, including IgG4 disease, sclerosing cholangitis, Mirizzi's syndrome, and recurrent pyogenic cholangitis. The role of PET in diagnosis and staging will also be discussed. Radiologists play a crucial role in diagnosis, staging, and treatment of this disease.","Source":"PubMed","category":"HUMAN","training_data":"Imaging spectrum of cholangiocarcinoma: role in diagnosis, staging, and posttreatment evaluation Cholangiocarcinoma, a tumor of biliary epithelium, is increasing in incidence. The imaging appearance, behavior, and treatment of cholangiocarcinoma differ according to its location and morphology. Cholangiocarcinoma is usually classified as intrahepatic, perihilar, or distal. The three morphologies are mass-forming, periductal sclerosing, and intraductal growing. As surgical resection is the only cure, prompt diagnosis and accurate staging is crucial. In staging, vascular involvement, longitudinal spread, and lymphadenopathy are important to assess. The role of liver transplantation for unresectable peripheral cholangiocarcinoma will be discussed. Locoregional therapy can extend survival for those with unresectable intrahepatic tumors. The main risk factors predisposing to cholangiocarcinoma are parasitic infections, primary sclerosing cholangitis, choledochal cysts, and viral hepatitis. Several inflammatory conditions can mimic cholangiocarcinoma, including IgG4 disease, sclerosing cholangitis, Mirizzi's syndrome, and recurrent pyogenic cholangitis. The role of PET in diagnosis and staging will also be discussed. Radiologists play a crucial role in diagnosis, staging, and treatment of this disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"programmed death ligand 1 expression human intrahepatic cholangiocarcinoma association prognosis cd8 cell immune responses background agents targeting programmed death ligand 1 pd l1 programmed death receptor 1 immune checkpoint exhibited promising clinical outcomes variety malignant tumors including intrahepatic cholangiocarcinoma icc however relationship pd l1 expression cd8 cell immune responses well defined icc patients methods investigated pd l1 expression immunohistochemistry formalin fixed paraffin embedded tissues 192 icc patients undergoing curative resection correlated results clinicopathologic features prognosis also quantified cd8 cell infiltration icc specimens evaluated relationship pd l1 expression cd8 cell infiltration incubating human icc cell lines hccc9810 rbe interferon ifn measured pd l1 expression icc cells western blot flow cytometry results 34 patients 17 7 showed 5 membranous pd l1 expression tumor cells tumoral pd l1 overexpression 5 significantly associated superior overall survival p 0 012 disease free survival p 0 018 significant positive association found pd l1 expression presence cd8 cells fresh frozen icc specimens ifn found significantly correlated pd l1 cd8a gene expression evaluated reverse transcription polymerase chain reaction moreover stimulation hccc9810 rbe cells recombinant ifn secreted cd8 cells rapidly induced pd l1 upregulation cell lines vitro conclusion tumor pd l1 overexpression mainly stimulated activated cd8 cells pre existing icc microenvironment pd l1 favorable prognostic factor patients observations suggest anti pd l1 programmed death receptor 1 therapy may benefit icc patients tumor cell pd l1 expression presence cd8 cells stn","probabilities":0.9467213,"Title":"Programmed Death Ligand 1 Expression In Human Intrahepatic Cholangiocarcinoma And Its Association With Prognosis And Cd8+ T-Cell Immune Responses","Abstract":"Background: Agents targeting the programmed death ligand 1 (PD-L1)/programmed death receptor 1 immune checkpoint exhibited promising clinical outcomes in a variety of malignant tumors, including intrahepatic cholangiocarcinoma (ICC). However, the relationship between PD-L1 expression and CD8+ T-cell immune responses is not well defined in ICC. \r\n\r\n Patients and methods: We investigated PD-L1 expression immunohistochemistry in formalin-fixed, paraffin-embedded tissues from 192 ICC patients undergoing curative resection and correlated our results with the clinicopathologic features and prognosis. We also quantified CD8+ T-cell infiltration in ICC specimens and evaluated the relationship between PD-L1 expression and CD8+ T-cell infiltration. After incubating human ICC cell lines (HCCC9810 and RBE) with interferon (IFN)-γ, we measured the PD-L1 expression of these ICC cells by Western blot and flow cytometry. \r\n\r\n Results: Only 34 patients (17.7%) showed ≥5% membranous PD-L1 expression on tumor cells, and tumoral PD-L1 overexpression (≥5%) was significantly associated with superior overall survival (P=0.012) and disease-free survival (P=0.018). A significant positive association was found between PD-L1 expression and the presence of CD8+ T-cells. In fresh frozen ICC specimens, IFN-γ was found to be significantly correlated with PD-L1 and CD8A gene expression, as evaluated by reverse transcription-polymerase chain reaction. Moreover, stimulation of the HCCC9810 and RBE cells with recombinant IFN-γ, secreted by CD8+ T-cells rapidly induced PD-L1 upregulation in these cell lines in vitro. \r\n\r\n Conclusion: Tumor PD-L1 overexpression is mainly stimulated by activated CD8+ T-cells pre-existing in the ICC microenvironment, and PD-L1 is a favorable prognostic factor for the patients. These observations suggest that anti-PD-L1/programmed death receptor 1 therapy may benefit ICC patients with tumor cell PD-L1 expression and the presence of CD8+ T-cells.","Source":"STN","category":"ANIMAL","training_data":"Programmed Death Ligand 1 Expression In Human Intrahepatic Cholangiocarcinoma And Its Association With Prognosis And Cd8+ T-Cell Immune Responses Background: Agents targeting the programmed death ligand 1 (PD-L1)/programmed death receptor 1 immune checkpoint exhibited promising clinical outcomes in a variety of malignant tumors, including intrahepatic cholangiocarcinoma (ICC). However, the relationship between PD-L1 expression and CD8+ T-cell immune responses is not well defined in ICC. \r\n\r\n Patients and methods: We investigated PD-L1 expression immunohistochemistry in formalin-fixed, paraffin-embedded tissues from 192 ICC patients undergoing curative resection and correlated our results with the clinicopathologic features and prognosis. We also quantified CD8+ T-cell infiltration in ICC specimens and evaluated the relationship between PD-L1 expression and CD8+ T-cell infiltration. After incubating human ICC cell lines (HCCC9810 and RBE) with interferon (IFN)-γ, we measured the PD-L1 expression of these ICC cells by Western blot and flow cytometry. \r\n\r\n Results: Only 34 patients (17.7%) showed ≥5% membranous PD-L1 expression on tumor cells, and tumoral PD-L1 overexpression (≥5%) was significantly associated with superior overall survival (P=0.012) and disease-free survival (P=0.018). A significant positive association was found between PD-L1 expression and the presence of CD8+ T-cells. In fresh frozen ICC specimens, IFN-γ was found to be significantly correlated with PD-L1 and CD8A gene expression, as evaluated by reverse transcription-polymerase chain reaction. Moreover, stimulation of the HCCC9810 and RBE cells with recombinant IFN-γ, secreted by CD8+ T-cells rapidly induced PD-L1 upregulation in these cell lines in vitro. \r\n\r\n Conclusion: Tumor PD-L1 overexpression is mainly stimulated by activated CD8+ T-cells pre-existing in the ICC microenvironment, and PD-L1 is a favorable prognostic factor for the patients. These observations suggest that anti-PD-L1/programmed death receptor 1 therapy may benefit ICC patients with tumor cell PD-L1 expression and the presence of CD8+ T-cells. STN","prediction_labels":"ANIMAL"},{"cleaned":"sulfated galactans red seaweed gracilaria fisheri exerts anti migration effect cholangiocarcinoma cells background seaweeds long history use asian countries functional foods medicinal herbs treatment cancer polysaccharides various seaweeds shown anti tumor activity cholangiocarcinoma cca often metastatic disease highly prevalent thailand consequence liver fluke infection recently extracted sulfated galactans sg gracilaria fisheri g fisheri south east asian seaweed found exhibited anti proliferation effect cca cells purpose present study evaluated anti migration activity sg cca cells underlined mechanism methods cca cells treated sg alone drugs targeting epidermal growth factor egf receptor egfr pretreated sg prior incubation egf anti migration activity determined using scratch wound healing assay zymography immunofluorescence staining western blotting used investigate egfr signaling mediators results basal condition sg reduced migration rate cca correlated decrease active form matrix metalloproteinases 9 sg decreased expression phosphorylated focal adhesion kinase fak increased expression e cadherin promote cells stasis moreover phosphorylation egfr extracellular signal regulated kinases erk known stimulate growth cancer cells blocked comparable way egfr inhibitors cetuximab erlotinib pretreatment cells sg attenuated egf induced phosphorylation egfr erk fak conclusion study reveals sg g fisheri retards migration cca cells mechanism inhibition mediated extent inhibitory effects mapk erk signal transduction pathway findings suggest may therapeutic potential sg cca treatment stn","probabilities":0.9799733,"Title":"Sulfated Galactans From The Red Seaweed Gracilaria Fisheri Exerts Anti-Migration Effect On Cholangiocarcinoma Cells","Abstract":"Background: Seaweeds have a long history of use in Asian countries as functional foods, medicinal herbs, and the treatment of cancer. Polysaccharides from various seaweeds have shown anti-tumor activity. Cholangiocarcinoma (CCA), often with metastatic disease, is highly prevalent in Thailand as a consequence of liver fluke infection. Recently, we extracted sulfated galactans (SG) from Gracilaria fisheri (G. fisheri), a south east Asian seaweed, and found it exhibited anti-proliferation effect on CCA cells. \r\n\r\n Purpose: In the present study, we evaluated the anti-migration activity of SG on CCA cells and its underlined mechanism. \r\n\r\n Methods: CCA cells were treated with SG alone or drugs targeting to epidermal growth factor (EGF) receptor (EGFR) or pretreated with SG prior to incubation with EGF. Anti-migration activity was determined using a scratch wound-healing assay and zymography. Immunofluorescence staining and western blotting were used to investigate EGFR signaling mediators. \r\n\r\n Results: Under basal condition, SG reduced the migration rate of CCA, which was correlated with a decrease in the active-form of matrix metalloproteinases-9. SG decreased expression of phosphorylated focal adhesion kinase (FAK), but increased expression of E-cadherin to promote cells stasis. Moreover, phosphorylation of EGFR and extracellular signal-regulated kinases (ERK), known to stimulate growth of cancer cells, was blocked in a comparable way to EGFR inhibitors Cetuximab and Erlotinib. Pretreatment cells with SG attenuated EGF induced phosphorylation of EGFR, ERK and FAK. \r\n\r\n Conclusion: This study reveals that SG from G. fisheri retards migration of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on MAPK/ERK signal transduction pathway. Our findings suggest that there may be a therapeutic potential of SG in CCA treatment.","Source":"STN","category":"ANIMAL","training_data":"Sulfated Galactans From The Red Seaweed Gracilaria Fisheri Exerts Anti-Migration Effect On Cholangiocarcinoma Cells Background: Seaweeds have a long history of use in Asian countries as functional foods, medicinal herbs, and the treatment of cancer. Polysaccharides from various seaweeds have shown anti-tumor activity. Cholangiocarcinoma (CCA), often with metastatic disease, is highly prevalent in Thailand as a consequence of liver fluke infection. Recently, we extracted sulfated galactans (SG) from Gracilaria fisheri (G. fisheri), a south east Asian seaweed, and found it exhibited anti-proliferation effect on CCA cells. \r\n\r\n Purpose: In the present study, we evaluated the anti-migration activity of SG on CCA cells and its underlined mechanism. \r\n\r\n Methods: CCA cells were treated with SG alone or drugs targeting to epidermal growth factor (EGF) receptor (EGFR) or pretreated with SG prior to incubation with EGF. Anti-migration activity was determined using a scratch wound-healing assay and zymography. Immunofluorescence staining and western blotting were used to investigate EGFR signaling mediators. \r\n\r\n Results: Under basal condition, SG reduced the migration rate of CCA, which was correlated with a decrease in the active-form of matrix metalloproteinases-9. SG decreased expression of phosphorylated focal adhesion kinase (FAK), but increased expression of E-cadherin to promote cells stasis. Moreover, phosphorylation of EGFR and extracellular signal-regulated kinases (ERK), known to stimulate growth of cancer cells, was blocked in a comparable way to EGFR inhibitors Cetuximab and Erlotinib. Pretreatment cells with SG attenuated EGF induced phosphorylation of EGFR, ERK and FAK. \r\n\r\n Conclusion: This study reveals that SG from G. fisheri retards migration of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on MAPK/ERK signal transduction pathway. Our findings suggest that there may be a therapeutic potential of SG in CCA treatment. STN","prediction_labels":"HUMAN"},{"cleaned":"outcomes resection solitary 5 cm intrahepatic cholangiocarcinoma background resection remains treatment choice achieving 5 year survival rates 22 40 aim analysis examine outcomes patients solitary 5 cm intrahepatic cholangiocarcinoma methods retrospective chart review performed 123 patients undergoing resection primary intrahepatic cholangiocarcinoma 1995 2013 group 1 included patients asymptomatic solitary intrahepatic cholangiocarcinoma measuring 5 cm results group 1 n 33 27 greater rate underlying liver disease cirrhosis minor resection favorable pathologic features including decreased rate perineural invasion vascular invasion lymph node involvement satellite nodules p 05 factors associated overall poor outcome patients group 2 p 025 positive margin p 04 presence satellite nodules p 008 multinodularity p 058 factors associated recurrence group 1 presence satellite nodules p 004 tumor size 4 cm p 031 factors associated decreased survival group 1 transfusion requirement p 0 018 5 year recurrence survival rates 39 vs 67 71 vs 53 group 1 versus group 2 respectively p 111 conclusion resection solitary intrahepatic cholangiocarcinoma 5 cm achieve 5 year survival rates 71 results comparable patients undergoing transplantation hepatocellular cancer within milan criteria pubmed","probabilities":0.9799733,"Title":"Outcomes of resection for solitary ≤5 cm intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Resection remains the treatment of choice achieving 5-year survival rates of 22% to 40%. The aim of this analysis was to examine the outcomes of patients with solitary ≤5 cm intrahepatic cholangiocarcinoma. METHODS: A retrospective chart review was performed on 123 patients undergoing resection for primary intrahepatic cholangiocarcinoma from 1995 to 2013. Group 1 included patients with asymptomatic solitary intrahepatic cholangiocarcinoma measuring ≤5 cm. RESULTS: Group 1 (n = 33, 27%) had a greater rate of underlying liver disease, cirrhosis, minor resection, favorable pathologic features including decreased rate of perineural invasion, vascular invasion, lymph node involvement, and satellite nodules (P < .05). Factors associated with overall poor outcome were patients in Group 2 (P=.025), positive margin (P=.04), presence of satellite nodules (P = .008), and multinodularity (P=.058). Factors associated with recurrence in Group 1 were presence of satellite nodules (P=.004), and tumor size ≥4 cm (P=.031). Factors associated with decreased survival in Group 1 was transfusion requirement (P = 0.018). The 5-year recurrence and survival rates were (39% vs 67%) and (71% vs 53%) in Group 1 versus Group 2, respectively (P=.111). CONCLUSION: Resection of solitary intrahepatic cholangiocarcinoma ≤5 cm can achieve 5-year survival rates up to 71%. Results were comparable to those of patients undergoing transplantation for hepatocellular cancer within the Milan criteria.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes of resection for solitary ≤5 cm intrahepatic cholangiocarcinoma BACKGROUND: Resection remains the treatment of choice achieving 5-year survival rates of 22% to 40%. The aim of this analysis was to examine the outcomes of patients with solitary ≤5 cm intrahepatic cholangiocarcinoma. METHODS: A retrospective chart review was performed on 123 patients undergoing resection for primary intrahepatic cholangiocarcinoma from 1995 to 2013. Group 1 included patients with asymptomatic solitary intrahepatic cholangiocarcinoma measuring ≤5 cm. RESULTS: Group 1 (n = 33, 27%) had a greater rate of underlying liver disease, cirrhosis, minor resection, favorable pathologic features including decreased rate of perineural invasion, vascular invasion, lymph node involvement, and satellite nodules (P < .05). Factors associated with overall poor outcome were patients in Group 2 (P=.025), positive margin (P=.04), presence of satellite nodules (P = .008), and multinodularity (P=.058). Factors associated with recurrence in Group 1 were presence of satellite nodules (P=.004), and tumor size ≥4 cm (P=.031). Factors associated with decreased survival in Group 1 was transfusion requirement (P = 0.018). The 5-year recurrence and survival rates were (39% vs 67%) and (71% vs 53%) in Group 1 versus Group 2, respectively (P=.111). CONCLUSION: Resection of solitary intrahepatic cholangiocarcinoma ≤5 cm can achieve 5-year survival rates up to 71%. Results were comparable to those of patients undergoing transplantation for hepatocellular cancer within the Milan criteria. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association hospital volume treatment patterns overall survival os patients intrahepatic cholangiocarcinoma ihcc background ihcc rare cancer poor os purpose study determine association number patients ihcc treated annually treatment facility volume different risk adjusted survival outcomes methods patients ihcc diagnosed 2004 2015 included classified facilities tertiles mean patients ihcc treated per year t1 2 56 t2 2 57 5 39 t3 5 40 used spss account clustering patients within centers based volumes lower middle higher 1 3rd cases cox regression determine volume outcome relationship adjusting covariates patient demographics tumor characteristics insurance therapy kaplan meier estimates 1 3 yr os compared log rank tests results total 11344 ihcc patients treated 1106 facilities median age diagnosis 65 years range 11 90 median annual facility volume 2 patients per year r 1 92 multivariable analysis showed facility volume independently associated cause mortality p 0 0001 unadjusted median os facility volume t1 5 months m t2 8 1 m t3 13 1 m p 0001 compared patients treated t3 facilities patients treated lower tertile facilities significantly higher risk death t2 hazard ratio hr 1 12 95 ci 1 05 1 23 t1 hr 1 21 ci 1 11 1 33 stage wise sub group analysis showed patients treated high volume centers likely get surgery 34 6 vs 13 1 adjuvant chemo radiation therapy chemo radiation therapy patterns similar among facilities receipt surgical therapy independently associated prolonged os conclusions patients treated ihcc high volume centers likely receive surgery adjuvant therapy significant improvement survival compared patients treated low volume facilities google scholar","probabilities":0.9799733,"Title":"Association Between Hospital Volume Treatment Patterns And Overall Survival (Os) Of Patients With Intrahepatic Cholangiocarcinoma (Ihcc)","Abstract":"Background: IHCC is a rare cancer with poor OS. The purpose of this study is to determine the association between the number of patients with IHCC treated annually at a treatment facility (volume) and different risk-adjusted survival outcomes. Methods: Patients with IHCC diagnosed between 2004 & 2015 were included. We classified facilities by tertiles (T; mean patients with IHCC treated per year): T1: < 2.56; T2: 2.57 – 5.39 and T3: ≥5.40. We used SPSS to account for clustering of patients within centers (based on the volumes: lower, middle & higher 1/3rd of the cases) and Cox regression to determine the volume-outcome relationship, adjusting for covariates-patient demographics, tumor characteristics, insurance & therapy. Kaplan Meier estimates of 1-, 3-yr OS were compared with log-rank tests. Results: Total of 11344 IHCC patients treated at 1106 facilities. The median age at diagnosis was 65 years (range, 11-90). The median annual facility volume was 2 patients per year (r, 1-92). Multivariable analysis showed that facility volume was independently associated with all-cause mortality (p < 0.0001). The unadjusted median OS by facility volume was: T1: 5 months (m), T2: 8.1 m, and T3: 13.1 m (p < .0001). Compared with patients treated at T3 facilities, patients treated at lower-tertile facilities had significantly higher risk of death [T2 hazard ratio (HR), 1.12 (95% CI, 1.05- 1.23); T1 HR, 1.21 (CI, 1.11 - 1.33)]. Stage-wise sub-group analysis showed that patients treated at high volume centers are more likely to get surgery (34.6 vs 13.1%) and adjuvant chemo and radiation therapy. Chemo and radiation therapy patterns were similar among facilities. Receipt of surgical therapy was independently associated with prolonged OS. Conclusions: Patients who were treated for IHCC at high-volume centers were more likely to receive surgery and adjuvant therapy and had a significant improvement in survival compared to that of patients treated at low- volume facilities.","Source":"Google Scholar","category":"HUMAN","training_data":"Association Between Hospital Volume Treatment Patterns And Overall Survival (Os) Of Patients With Intrahepatic Cholangiocarcinoma (Ihcc) Background: IHCC is a rare cancer with poor OS. The purpose of this study is to determine the association between the number of patients with IHCC treated annually at a treatment facility (volume) and different risk-adjusted survival outcomes. Methods: Patients with IHCC diagnosed between 2004 & 2015 were included. We classified facilities by tertiles (T; mean patients with IHCC treated per year): T1: < 2.56; T2: 2.57 – 5.39 and T3: ≥5.40. We used SPSS to account for clustering of patients within centers (based on the volumes: lower, middle & higher 1/3rd of the cases) and Cox regression to determine the volume-outcome relationship, adjusting for covariates-patient demographics, tumor characteristics, insurance & therapy. Kaplan Meier estimates of 1-, 3-yr OS were compared with log-rank tests. Results: Total of 11344 IHCC patients treated at 1106 facilities. The median age at diagnosis was 65 years (range, 11-90). The median annual facility volume was 2 patients per year (r, 1-92). Multivariable analysis showed that facility volume was independently associated with all-cause mortality (p < 0.0001). The unadjusted median OS by facility volume was: T1: 5 months (m), T2: 8.1 m, and T3: 13.1 m (p < .0001). Compared with patients treated at T3 facilities, patients treated at lower-tertile facilities had significantly higher risk of death [T2 hazard ratio (HR), 1.12 (95% CI, 1.05- 1.23); T1 HR, 1.21 (CI, 1.11 - 1.33)]. Stage-wise sub-group analysis showed that patients treated at high volume centers are more likely to get surgery (34.6 vs 13.1%) and adjuvant chemo and radiation therapy. Chemo and radiation therapy patterns were similar among facilities. Receipt of surgical therapy was independently associated with prolonged OS. Conclusions: Patients who were treated for IHCC at high-volume centers were more likely to receive surgery and adjuvant therapy and had a significant improvement in survival compared to that of patients treated at low- volume facilities. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"assessment clinical outcome cholecystectomy according age preparation silver tsunami background recent rapid increases aging population created impending silver tsunami advanced countries overall prevalence gallstone disease related complications soon increase larger demand gallbladder surgery methods examined outcomes cholecystectomy according age among patients cholelithiasis determine patient age influences outcome cholecystectomy patients gallstone disease presented cholecystectomy institute january 2006 december 2018 analyzed results perioperative outcomes operation length length hospital stay rate open surgery urgent surgery postoperative complications incidental gallbladder cancer postoperative hospital death concomitant bile duct stones total medical costs per patient increased patients aged conclusions prevent progression biliary disease elective laparoscopic cholecystectomy recommended patients cholelithiasis advance age pubmed","probabilities":0.9799733,"Title":"Assessment of clinical outcome of cholecystectomy according to age in preparation for the Silver Tsunami","Abstract":"BACKGROUND: Recent rapid increases in the aging population have created an impending \"Silver Tsunami\" in advanced countries. The overall prevalence of gallstone disease and its related complications will soon increase, and there will be a larger demand for gallbladder surgery. METHODS: We examined the outcomes of cholecystectomy according to age among patients with cholelithiasis to determine how a patient's age influences the outcome of cholecystectomy. All patients with gallstone disease who presented for cholecystectomy at our institute from January 2006 to December 2018 were analyzed. RESULTS: All perioperative outcomes (operation length, length of hospital stay, rate of open surgery, urgent surgery, postoperative complications, incidental gallbladder cancer, postoperative hospital death, concomitant bile duct stones, and total medical costs per patient) increased as patients aged. CONCLUSIONS: To prevent the progression of biliary disease, elective laparoscopic cholecystectomy is recommended before patients with cholelithiasis advance in age.","Source":"PubMed","category":"HUMAN","training_data":"Assessment of clinical outcome of cholecystectomy according to age in preparation for the Silver Tsunami BACKGROUND: Recent rapid increases in the aging population have created an impending \"Silver Tsunami\" in advanced countries. The overall prevalence of gallstone disease and its related complications will soon increase, and there will be a larger demand for gallbladder surgery. METHODS: We examined the outcomes of cholecystectomy according to age among patients with cholelithiasis to determine how a patient's age influences the outcome of cholecystectomy. All patients with gallstone disease who presented for cholecystectomy at our institute from January 2006 to December 2018 were analyzed. RESULTS: All perioperative outcomes (operation length, length of hospital stay, rate of open surgery, urgent surgery, postoperative complications, incidental gallbladder cancer, postoperative hospital death, concomitant bile duct stones, and total medical costs per patient) increased as patients aged. CONCLUSIONS: To prevent the progression of biliary disease, elective laparoscopic cholecystectomy is recommended before patients with cholelithiasis advance in age. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment borderline cases curative resection biliary tract cancer background aim dissect high rate non curative resection associated biliary tract cancer compared outcome non curative resection inoperable cancer patients referred surgery methods retrospectively analyzed 447 patients biliary tract cancer referred hospital 1970 2008 compared background overall survival os rates accordingly surgery curative resection non curative resection surgery inoperable alternative therapies chemotherapy radiotherapy results 3 year os rate 19 non curative resection group n 72 2 inoperable group n 135 p 0 0001 among inoperable cases 3 year os rate patient received chemotherapy including gemcitabine gem 18 n 18 similar patients non curative resection treated gem p 0 7379 significant differences survival non curative resection without gem inoperable cases gem based chemotherapy conclusion results indicate prognosis patients undergo non curative surgery better inoperable cancer similar receive chemotherapy including gem pubmed","probabilities":0.9799733,"Title":"Treatment of borderline cases for curative resection of biliary tract cancer","Abstract":"BACKGROUND AND AIM: To dissect the high rate of non-curative resection associated with biliary tract cancer, we compared the outcome of non-curative resection with that of inoperable cancer in patients referred for surgery. METHODS: We retrospectively analyzed 447 patients with biliary tract cancer who were referred to our hospital between 1970 and 2008. We compared the background and overall survival (OS) rates accordingly to surgery (curative resection, non-curative resection, or no surgery \"inoperable\") and alternative therapies (chemotherapy and/or radiotherapy). RESULTS: The 3-year OS rate was 19% for the non-curative resection group (n=72) and 2% for the inoperable group (n=135, P<0.0001). Among the inoperable cases, the 3-year OS rate for patient who received chemotherapy, including gemcitabine (GEM), was 18% (n=18), which was similar to that of patients of the non-curative resection who were treated with GEM (P=0.7379). There were no significant differences in survival between non-curative resection without GEM and inoperable cases with GEM-based chemotherapy. CONCLUSION: Our results indicate that the prognosis of patients who undergo non-curative surgery is better than those with inoperable cancer, but similar to those who receive chemotherapy including GEM.","Source":"PubMed","category":"HUMAN","training_data":"Treatment of borderline cases for curative resection of biliary tract cancer BACKGROUND AND AIM: To dissect the high rate of non-curative resection associated with biliary tract cancer, we compared the outcome of non-curative resection with that of inoperable cancer in patients referred for surgery. METHODS: We retrospectively analyzed 447 patients with biliary tract cancer who were referred to our hospital between 1970 and 2008. We compared the background and overall survival (OS) rates accordingly to surgery (curative resection, non-curative resection, or no surgery \"inoperable\") and alternative therapies (chemotherapy and/or radiotherapy). RESULTS: The 3-year OS rate was 19% for the non-curative resection group (n=72) and 2% for the inoperable group (n=135, P<0.0001). Among the inoperable cases, the 3-year OS rate for patient who received chemotherapy, including gemcitabine (GEM), was 18% (n=18), which was similar to that of patients of the non-curative resection who were treated with GEM (P=0.7379). There were no significant differences in survival between non-curative resection without GEM and inoperable cases with GEM-based chemotherapy. CONCLUSION: Our results indicate that the prognosis of patients who undergo non-curative surgery is better than those with inoperable cancer, but similar to those who receive chemotherapy including GEM. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma epidemiology risk factors cholangiocarcinoma cca heterogeneous disease arising complex interaction host specific genetic background multiple risk factors globally cca incidence rates exhibit geographical variation much higher incidence parts eastern world compared west differences likely reflect differences geographical risk factors well genetic determinants note past decades incidence rates cca appear change subtypes cca appear show distinct epidemiological trends trends need interpreted caution given issues diagnosis recording coding subtypes cca epidemiological evidences suggest general population risk factors less frequent associated higher cca risk others common associated lower risk moreover risk factors shared intrahepatic extrahepatic forms others seem specific one two forms currently pathological conditions clearly associated cca development conditions emerging however impact increasing cca risk single etiological factors provided many studies less known two risk factors co occur patient moreover despite advancements knowledge cca aetiology western countries 50 cases still diagnosed without identifiable risk factor therefore conceivable still undefined etiologic factors responsible recent increase cca especially icca incidence worldwide pubmed","probabilities":0.9799733,"Title":"Cholangiocarcinoma: Epidemiology and risk factors","Abstract":"Cholangiocarcinoma (CCA) is a heterogeneous disease arising from a complex interaction between host-specific genetic background and multiple risk factors. Globally, CCA incidence rates exhibit geographical variation, with much higher incidence in parts of the Eastern world compared to the West. These differences are likely to reflect differences in geographical risk factors as well as genetic determinants. Of note, over the past few decades, the incidence rates of CCA appear to change and subtypes of CCA appear to show distinct epidemiological trends. These trends need to be interpreted with caution given the issues of diagnosis, recording and coding of subtypes of CCA. Epidemiological evidences suggest that in general population some risk factors are less frequent but associated with a higher CCA risk, while others are more common but associated with a lower risk. Moreover, while some risk factors are shared by intrahepatic and both extrahepatic forms, others seem more specific for one of the two forms. Currently some pathological conditions have been clearly associated with CCA development, and other conditions are emerging; however, while their impact in increasing CCA risk as single etiological factors has been provided in many studies, less is known when two or more risk factors co-occur in the same patient. Moreover, despite the advancements in the knowledge of CCA aetiology, in Western countries about 50% of cases are still diagnosed without any identifiable risk factor. It is therefore conceivable that other still undefined etiologic factors are responsible for the recent increase of CCA (especially iCCA) incidence worldwide.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma: Epidemiology and risk factors Cholangiocarcinoma (CCA) is a heterogeneous disease arising from a complex interaction between host-specific genetic background and multiple risk factors. Globally, CCA incidence rates exhibit geographical variation, with much higher incidence in parts of the Eastern world compared to the West. These differences are likely to reflect differences in geographical risk factors as well as genetic determinants. Of note, over the past few decades, the incidence rates of CCA appear to change and subtypes of CCA appear to show distinct epidemiological trends. These trends need to be interpreted with caution given the issues of diagnosis, recording and coding of subtypes of CCA. Epidemiological evidences suggest that in general population some risk factors are less frequent but associated with a higher CCA risk, while others are more common but associated with a lower risk. Moreover, while some risk factors are shared by intrahepatic and both extrahepatic forms, others seem more specific for one of the two forms. Currently some pathological conditions have been clearly associated with CCA development, and other conditions are emerging; however, while their impact in increasing CCA risk as single etiological factors has been provided in many studies, less is known when two or more risk factors co-occur in the same patient. Moreover, despite the advancements in the knowledge of CCA aetiology, in Western countries about 50% of cases are still diagnosed without any identifiable risk factor. It is therefore conceivable that other still undefined etiologic factors are responsible for the recent increase of CCA (especially iCCA) incidence worldwide. PubMed","prediction_labels":"HUMAN"},{"cleaned":"laparoscopic pancreaticoduodenectomy periampullary tumors lessons learned 500 consecutive patients single center background laparoscopic pancreaticoduodenectomy lpd feasible option selected patients however use yet generalized since time consuming physically demanding technically challenging might essential share experience high volume centers understand use methods retrospectively reviewed data 500 consecutive patients underwent lpd single institution january 2007 december 2017 results patients included 272 women 228 men mean age 57 1 years common indication lpd intraductal papillary neoplasm n 104 20 8 overall major clavien dindo grades iii v complication rates 37 2 4 8 respectively fifty four patients 10 8 clinically relevant grade b c pancreatic fistulas 3 0 6 90 day mortalities common late complication bilioenteric stricture 25 5 two hundred thirty patients diagnosed periampullary cancer 5 year overall survival rates pancreatic cancer common bile duct cancer ampulla vater cancer duodenal cancer 37 4 63 2 78 88 9 respectively analyzed learning curves first generation second generation surgeons risk adjusted cumulative sum analysis demonstrated learning curve 55 cases lpd first generation surgeon earlier competency second generation surgeon conclusions lpd potential become alternative surgery open pancreaticoduodenectomy periampullary tumors acceptable outcomes reduce steep learning curve structured training close supervision well trained operation teams perioperative oncologic outcomes lpd optimized overcoming learning curve stn","probabilities":0.9799733,"Title":"Laparoscopic Pancreaticoduodenectomy For Periampullary Tumors: Lessons Learned From 500 Consecutive Patients In A Single Center","Abstract":"Background: Laparoscopic pancreaticoduodenectomy (LPD) is a feasible option in selected patients. However, its use has not yet been generalized since it is time-consuming, physically demanding, and technically challenging. It might be essential to share the experience of high-volume centers to understand its use. \r\n\r\n Methods: We retrospectively reviewed the data of 500 consecutive patients who underwent LPD at a single institution between January 2007 and December 2017. \r\n\r\n Results: The patients included 272 women and 228 men (mean age, 57.1 years). The most common indication for LPD was intraductal papillary neoplasm (n = 104, 20.8%). Overall and major (Clavien-Dindo grades III-V) complication rates were 37.2% and 4.8%, respectively. Fifty-four patients (10.8%) had clinically relevant (grade B/C) pancreatic fistulas. There were 3 (0.6%) 90-day mortalities. The most common late complication was bilioenteric stricture (25, 5%). Two hundred thirty patients were diagnosed with periampullary cancer. The 5-year overall survival rates of pancreatic cancer, common bile duct cancer, ampulla of Vater cancer, and duodenal cancer were 37.4, 63.2, 78, and 88.9%, respectively. We analyzed learning curves of first-generation and second-generation surgeons. A risk-adjusted cumulative sum analysis demonstrated a learning curve of 55 cases for LPD with the first-generation surgeon and earlier competency with the second-generation surgeon. \r\n\r\n Conclusions: LPD has the potential to become an alternative surgery to open pancreaticoduodenectomy for periampullary tumors with acceptable outcomes. We could reduce the steep learning curve with structured training, close supervision, and well-trained operation teams. Perioperative and oncologic outcomes of LPD will be optimized after overcoming the learning curve.","Source":"STN","category":"HUMAN","training_data":"Laparoscopic Pancreaticoduodenectomy For Periampullary Tumors: Lessons Learned From 500 Consecutive Patients In A Single Center Background: Laparoscopic pancreaticoduodenectomy (LPD) is a feasible option in selected patients. However, its use has not yet been generalized since it is time-consuming, physically demanding, and technically challenging. It might be essential to share the experience of high-volume centers to understand its use. \r\n\r\n Methods: We retrospectively reviewed the data of 500 consecutive patients who underwent LPD at a single institution between January 2007 and December 2017. \r\n\r\n Results: The patients included 272 women and 228 men (mean age, 57.1 years). The most common indication for LPD was intraductal papillary neoplasm (n = 104, 20.8%). Overall and major (Clavien-Dindo grades III-V) complication rates were 37.2% and 4.8%, respectively. Fifty-four patients (10.8%) had clinically relevant (grade B/C) pancreatic fistulas. There were 3 (0.6%) 90-day mortalities. The most common late complication was bilioenteric stricture (25, 5%). Two hundred thirty patients were diagnosed with periampullary cancer. The 5-year overall survival rates of pancreatic cancer, common bile duct cancer, ampulla of Vater cancer, and duodenal cancer were 37.4, 63.2, 78, and 88.9%, respectively. We analyzed learning curves of first-generation and second-generation surgeons. A risk-adjusted cumulative sum analysis demonstrated a learning curve of 55 cases for LPD with the first-generation surgeon and earlier competency with the second-generation surgeon. \r\n\r\n Conclusions: LPD has the potential to become an alternative surgery to open pancreaticoduodenectomy for periampullary tumors with acceptable outcomes. We could reduce the steep learning curve with structured training, close supervision, and well-trained operation teams. Perioperative and oncologic outcomes of LPD will be optimized after overcoming the learning curve. STN","prediction_labels":"HUMAN"},{"cleaned":"serum liver enzymes serve prognostic factors patients intrahepatic cholangiocarcinoma objective liver functions reflective overall status host reported important factors affecting prognosis many types cancers study explored influences liver enzymes albumin alb globulin gelo total protein tp alkaline phosphatase alp alanine aminotransferase alt aspartate aminotransferase ast total bilirubin tbil direct bilirubin dbil gamma glutamyltranspeptidase ggt lactate dehydrogenase ldh overall survival os number 173 patients intrahepatic cholangiocarcinoma icc patients methods 2011 2015 enrolled patients pathologically proven locally advanced metastatic icc impact alb gelo tp alp alt ast tbil dbil ggt ldh os analyzed using kaplan meier analysis next associations liver enzymes os evaluated univariate multivariate analyses finally role enzymes os evaluated subgroups results elevated liver enzymes linked os revealed independent prognostic factors poor outcome alp tbil dbil ggt whereas alb protective factor icc patients conclusion results demonstrate liver enzymes may serve valuable predictive markers icc patients google scholar","probabilities":0.9799733,"Title":"Serum Liver Enzymes Serve As Prognostic Factors In Patients With Intrahepatic Cholangiocarcinoma","Abstract":"Objective\nLiver functions, reflective of the overall status of the host, have been reported to be important factors affecting the prognosis in many types of cancers. In this study, we explored the influences of liver enzymes albumin (ALB), globulin (GELO), total protein (TP), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma glutamyltranspeptidase (GGT), and lactate dehydrogenase (LDH) on the overall survival (OS) in a number of 173 patients with intrahepatic cholangiocarcinoma (ICC).\n\nPatients and methods\nBetween 2011 and 2015, we enrolled patients with pathologically proven locally advanced or metastatic ICC. The impact of ALB, GELO, TP, ALP, ALT, AST, TBIL, DBIL, GGT, and LDH on OS were analyzed using Kaplan–Meier analysis. Next, the associations between these liver enzymes and OS were evaluated by univariate and multivariate analyses. Finally, the role of these enzymes in OS was evaluated in the subgroups.\n\nResults\nElevated liver enzymes were linked with OS. We revealed that independent prognostic factors of poor outcome were ALP, TBIL, DBIL, and GGT, whereas ALB is a protective factor in ICC patients.\nConclusion\nOur results demonstrate that these liver enzymes may serve as valuable predictive markers in ICC patients.","Source":"Google Scholar","category":"HUMAN","training_data":"Serum Liver Enzymes Serve As Prognostic Factors In Patients With Intrahepatic Cholangiocarcinoma Objective\nLiver functions, reflective of the overall status of the host, have been reported to be important factors affecting the prognosis in many types of cancers. In this study, we explored the influences of liver enzymes albumin (ALB), globulin (GELO), total protein (TP), alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma glutamyltranspeptidase (GGT), and lactate dehydrogenase (LDH) on the overall survival (OS) in a number of 173 patients with intrahepatic cholangiocarcinoma (ICC).\n\nPatients and methods\nBetween 2011 and 2015, we enrolled patients with pathologically proven locally advanced or metastatic ICC. The impact of ALB, GELO, TP, ALP, ALT, AST, TBIL, DBIL, GGT, and LDH on OS were analyzed using Kaplan–Meier analysis. Next, the associations between these liver enzymes and OS were evaluated by univariate and multivariate analyses. Finally, the role of these enzymes in OS was evaluated in the subgroups.\n\nResults\nElevated liver enzymes were linked with OS. We revealed that independent prognostic factors of poor outcome were ALP, TBIL, DBIL, and GGT, whereas ALB is a protective factor in ICC patients.\nConclusion\nOur results demonstrate that these liver enzymes may serve as valuable predictive markers in ICC patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"surgery gallbladder cancer us greater need radical cholecystectomy maximal lymph node clearance background gallbladder cancer gbc uncommon cancer poor overall survival frequent local metastatic relapse gbc often identified incidentally cholecystectomy case reoperation portal lymph node dissection lnd frequently performed value lnd staging therapeutic value continues debated particular optimal extent lymph node clearance unclear methods surveillance epidemiology end results seer database queried patients diagnosed gbc overall survival analyzed using kaplan meier method comparedusinglogranktesting coxproportionalhazardmodelingwasusedinmultivariate analysis identify predictors survival using age type surgery simple vs radical cholecystectomy adjuvant treatment stage number lymph nodes examined addition contribution survival minimal lnd min lnd 1 3 ln removed vs maximal lnd max lnd 3 ln removed evaluated separately within tumor stages iiib predictors patients undergo max lnd also evaluated results total 12 962 patients gallbladder cancer identified included 11 113 patients without distant metastases analysis multivariate analysis stage iiib gbc demonstrated strong predictors improved survival early tumor status negative lns adjuvant treatments p 0 001 predictors worse overall survival simple cholecystectomy hr 1 74 p 0 001 minimal lnd hr 2 56 p 0 001 evaluated tumor stage extent ln removal significantly affect mean overall survival stage gbc contrast extent lnd gbc significantly associated improved overall survival patients stage ii t2n0 stage iiia t3n0 stage iiib t1 3 n1 disease p 0 01 see table likelihood max lnd performed predicted younger age p 0 001 well t4 tumor status compared t1 3 p 001 lns recovered 74 60 50 patients stage ii iii disease respectively conclusions largest population based study patients gbc literature surprisingly early tumor stage adjuvant therapy correlate survival addition found radical cholecystectomy maximal lnd correlate survival even node negative patients stage ii iiia results support approach radical cholecystectomy extensive ln dissection stage ii iii disease also suggest many patients us gbc currently surgically undertreated thesepatientsmaynotbereceivingthebestchanceforcontrolofanotherwise difficult disease finally finding lnd benefits patients n0 disease raises questions current methods ln analysis google scholar","probabilities":0.9799733,"Title":"Surgery For Gallbladder Cancer In The Us: Greater Need For Radical Cholecystectomy And Maximal Lymph Node Clearance","Abstract":"Background: Gallbladder cancer (GBC) is an uncommon cancer with poor overall survival and frequent local and metastatic relapse. GBC is often identified incidentally after cholecystectomy, in which case reoperation with portal lymph node dissection (LND) is frequently performed. The value of LND both for its staging and therapeutic value continues to be debated. In particular, the optimal extent of lymph node clearance is unclear. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients diagnosed with GBC. Overall survival was analyzed using the Kaplan-Meier method and comparedusingLogranktesting.Coxproportionalhazardmodelingwasusedinmultivariate analysis to identify predictors of survival using age, type of surgery (simple vs radical cholecystectomy), adjuvant treatment, stage, and number of lymph nodes examined. In addition, the contribution to survival of minimal LND (min-LND; 1-3 LN removed) vs maximal LND (max-LND; .3 LN removed) was evaluated separately within each of tumor Stages I-IIIB. Predictors that patients would undergo max-LND were also evaluated. Results: A total of 12,962 patients with gallbladder cancer were identified. We included 11,113 patients without distant metastases in our analysis. Multivariate analysis of Stage I-IIIB GBC demonstrated that strong predictors of improved survival are early tumor status, negative LNs and adjuvant treatments (p,0.001 for all). Predictors of worse overall survival are simple cholecystectomy (HR 1.74; p,0.001) and minimal LND (HR 2.56; p,0.001). When evaluated by tumor stage, the extent of LN removal did not significantly affect mean overall survival of Stage I GBC. In contrast, the extent of LND for GBC was significantly associated with improved overall survival of patients with Stage II (T2N0), Stage IIIA (T3N0) and Stage IIIB (T1-3,N1) disease (p,0.01 for all; see Table). The likelihood that max-LND was performed was predicted by younger age (p,0.001), as well as T4 tumor status compared to T1-3 (p,.001). No LNs were recovered in 74%, 60% and 50% of patients with Stage I, II and III disease respectively. Conclusions: This is the largest population-based study of patients with GBC in the literature. Not surprisingly, early tumor stage and adjuvant therapy correlate with survival. In addition we found radical cholecystectomy and maximal LND correlate with survival even in node negative patients (Stage II and IIIA). Our results support an approach of radical cholecystectomy and extensive LN dissection for Stage II and III disease, and also suggest that many patients in the US with GBC are currently surgically undertreated.Thesepatientsmaynotbereceivingthebestchanceforcontrolofanotherwise difficult disease. Finally, the finding that LND benefits patients with N0 disease raises questions about current methods of LN analysis.","Source":"Google Scholar","category":"HUMAN","training_data":"Surgery For Gallbladder Cancer In The Us: Greater Need For Radical Cholecystectomy And Maximal Lymph Node Clearance Background: Gallbladder cancer (GBC) is an uncommon cancer with poor overall survival and frequent local and metastatic relapse. GBC is often identified incidentally after cholecystectomy, in which case reoperation with portal lymph node dissection (LND) is frequently performed. The value of LND both for its staging and therapeutic value continues to be debated. In particular, the optimal extent of lymph node clearance is unclear. Methods: The Surveillance, Epidemiology, and End Results (SEER) database was queried for patients diagnosed with GBC. Overall survival was analyzed using the Kaplan-Meier method and comparedusingLogranktesting.Coxproportionalhazardmodelingwasusedinmultivariate analysis to identify predictors of survival using age, type of surgery (simple vs radical cholecystectomy), adjuvant treatment, stage, and number of lymph nodes examined. In addition, the contribution to survival of minimal LND (min-LND; 1-3 LN removed) vs maximal LND (max-LND; .3 LN removed) was evaluated separately within each of tumor Stages I-IIIB. Predictors that patients would undergo max-LND were also evaluated. Results: A total of 12,962 patients with gallbladder cancer were identified. We included 11,113 patients without distant metastases in our analysis. Multivariate analysis of Stage I-IIIB GBC demonstrated that strong predictors of improved survival are early tumor status, negative LNs and adjuvant treatments (p,0.001 for all). Predictors of worse overall survival are simple cholecystectomy (HR 1.74; p,0.001) and minimal LND (HR 2.56; p,0.001). When evaluated by tumor stage, the extent of LN removal did not significantly affect mean overall survival of Stage I GBC. In contrast, the extent of LND for GBC was significantly associated with improved overall survival of patients with Stage II (T2N0), Stage IIIA (T3N0) and Stage IIIB (T1-3,N1) disease (p,0.01 for all; see Table). The likelihood that max-LND was performed was predicted by younger age (p,0.001), as well as T4 tumor status compared to T1-3 (p,.001). No LNs were recovered in 74%, 60% and 50% of patients with Stage I, II and III disease respectively. Conclusions: This is the largest population-based study of patients with GBC in the literature. Not surprisingly, early tumor stage and adjuvant therapy correlate with survival. In addition we found radical cholecystectomy and maximal LND correlate with survival even in node negative patients (Stage II and IIIA). Our results support an approach of radical cholecystectomy and extensive LN dissection for Stage II and III disease, and also suggest that many patients in the US with GBC are currently surgically undertreated.Thesepatientsmaynotbereceivingthebestchanceforcontrolofanotherwise difficult disease. Finally, the finding that LND benefits patients with N0 disease raises questions about current methods of LN analysis. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"therapeutic efficacy silvestrol novel protein translation inhibitor anticancer agent cholangiocarcinoma background survival unresectable cholangiocarcinoma poor cancers highly refractory therapy tumor growth requires new protein synthesis shown modulation protein translation enhance therapeutic responses thus evaluated therapeutic potential silvestrol rocaglate aglaia foveolata unique structure inhibits translation initiation eukaryotic initiation factor 4a methods cell growth assessed mzcha 1 mz il 6 kmch 1 cclp 1 tfk 1 humancholangiocarcinomacells usingaviablecellassay apoptosiswasassessedmorphologically caspase 3 7 activation using luminometric assay mitochondrial membrane potential mmp detected using jc 1 expression anti apoptotic mcl 1 protein immunoblotting interactions silvestrol gemcitabine cisplatin analyzed using calcusyn program vivo efficacy silvestrol evaluated using subcutaneous mz il 6 cell xenograft model athymic nude mice received 0 1 dmso saline diluent control silvestrol 1 mg kg body weight 5 days week p 4 weeks tumor growth monitored twice weekly caliper measurements results silvestrol inhibited tumor cell growth concentration dependent manner ic50 8 8 nm mzcha 1 8 0 nm mz il 6 38 0 nm kmch 1 2 0 nm cclp 1 16 5 nm tfk 1 cells incubation 100 nm silvestrol 24 hrs induced apoptosis 16 2 mzcha 1 38 7 kmch 1 cells increase caspase 3 7 activity 2 1foldinmzcha 1and2 3 foldinkmch 1cells anincreaseinmonomericjc 1fluorescence hence loss mmp occurred decrease mcl 1 protein expression 67 24 hrs despite increase mcl 1 mrna mzcha 1 cells vitro silvestrol combined withothertherapeuticagentsresultedinadose reductionindexof7 4 foldwithgemcitabine 9 2 fold cisplatin 50 cytotoxicity vivo treatment tumor cell xenografts either silvestrol diluent control well tolerated significant weight loss difference weights groups dramatic antitumor effect observed reduction mean tumor volume 43 2 day 22 62 3 day 29 treated group compared control group tumor weight sacrifice day 32 silvestroltreated mice 62 6 decreased compared control group p 0 02 conclusion silvestrol novel therapeutic agent highly potent vitro vivo antitumor activity cholangiocarcinoma studies highlight use structurally unique class potential anticancer drugs rocaglates novel mechanism drug action targeting protein translation developing effective therapies refractory cancers cholangiocarcinoma google scholar","probabilities":0.9467213,"Title":"Therapeutic Efficacy Of Silvestrol A Novel Protein Translation Inhibitor As An Anticancer Agent For Cholangiocarcinoma","Abstract":"Background: Survival from unresectable cholangiocarcinoma is poor because these cancers are highly refractory to therapy. Tumor growth requires new protein synthesis and we have shown that modulation of protein translation can enhance therapeutic responses. Thus, we evaluated the therapeutic potential of silvestrol, a rocaglate from Aglaia foveolata with a unique structure that inhibits translation initiation through eukaryotic initiation factor 4A. Methods: Cell growth was assessed in MzChA-1, Mz-IL-6, KMCH-1, CCLP-1 and TFK-1 humancholangiocarcinomacells usingaviablecellassay. Apoptosiswasassessedmorphologically and caspase-3/7 activation using a luminometric assay. Mitochondrial membrane potential (MMP) was detected using JC-1, and expression of anti-apoptotic Mcl-1 protein by immunoblotting. Interactions between silvestrol and gemcitabine or cisplatin were analyzed using Calcusyn program. In Vivo efficacy of silvestrol was evaluated using a subcutaneous Mz-IL-6 cell xenograft model in athymic nude mice that received 0.1% DMSO/saline (diluent control) or silvestrol 1 mg/kg body weight for 5 days a week i.p. for 4 weeks. Tumor growth was monitored by twice weekly caliper measurements. Results: Silvestrol inhibited tumor cell growth in a concentration-dependent manner with an IC50 of 8.8 nM in MzChA-1, 8.0 nM in Mz-IL-6, 38.0 nM in KMCH-1, 2.0 nM in CCLP-1 and 16.5 nM in TFK-1 cells. Incubation with 100 nM silvestrol for 24 hrs induced apoptosis by 16.2% in MzChA-1 and 38.7% in KMCH-1 cells, with an increase in caspase-3/7 activity by 2.1foldinMzChA-1and2.3-foldinKMCH-1cells.AnincreaseinmonomericJC-1fluorescence, and hence loss of MMP occurred, with a decrease in Mcl-1 protein expression by 67% after 24 hrs despite an increase in Mcl-1 mRNA in MzChA-1 cells. In Vitro, silvestrol combined withothertherapeuticagentsresultedinadose-reductionindexof7.4-foldwithgemcitabine and 9.2-fold with cisplatin for 50% cytotoxicity. In Vivo treatment of tumor cell xenografts with either silvestrol, or diluent control was well tolerated with no significant weight loss or difference in weights between the groups. A dramatic antitumor effect was observed with a reduction in mean tumor volume of 43.2% by day 22 and 62.3% at day 29 in the treated group compared to the control group. The tumor weight at sacrifice (day 32) in silvestroltreated mice was 62.6% decreased compared to the control group (p = 0.02). Conclusion: Silvestrol is a novel therapeutic agent with highly potent In Vitro and In Vivo antitumor activity against cholangiocarcinoma. These studies highlight the use of both a structurally unique class of potential anticancer drugs (rocaglates)and a novel mechanism of drug action (targeting protein translation) in developing effective therapies for refractory cancers such as cholangiocarcinoma.","Source":"Google Scholar","category":"ANIMAL","training_data":"Therapeutic Efficacy Of Silvestrol A Novel Protein Translation Inhibitor As An Anticancer Agent For Cholangiocarcinoma Background: Survival from unresectable cholangiocarcinoma is poor because these cancers are highly refractory to therapy. Tumor growth requires new protein synthesis and we have shown that modulation of protein translation can enhance therapeutic responses. Thus, we evaluated the therapeutic potential of silvestrol, a rocaglate from Aglaia foveolata with a unique structure that inhibits translation initiation through eukaryotic initiation factor 4A. Methods: Cell growth was assessed in MzChA-1, Mz-IL-6, KMCH-1, CCLP-1 and TFK-1 humancholangiocarcinomacells usingaviablecellassay. Apoptosiswasassessedmorphologically and caspase-3/7 activation using a luminometric assay. Mitochondrial membrane potential (MMP) was detected using JC-1, and expression of anti-apoptotic Mcl-1 protein by immunoblotting. Interactions between silvestrol and gemcitabine or cisplatin were analyzed using Calcusyn program. In Vivo efficacy of silvestrol was evaluated using a subcutaneous Mz-IL-6 cell xenograft model in athymic nude mice that received 0.1% DMSO/saline (diluent control) or silvestrol 1 mg/kg body weight for 5 days a week i.p. for 4 weeks. Tumor growth was monitored by twice weekly caliper measurements. Results: Silvestrol inhibited tumor cell growth in a concentration-dependent manner with an IC50 of 8.8 nM in MzChA-1, 8.0 nM in Mz-IL-6, 38.0 nM in KMCH-1, 2.0 nM in CCLP-1 and 16.5 nM in TFK-1 cells. Incubation with 100 nM silvestrol for 24 hrs induced apoptosis by 16.2% in MzChA-1 and 38.7% in KMCH-1 cells, with an increase in caspase-3/7 activity by 2.1foldinMzChA-1and2.3-foldinKMCH-1cells.AnincreaseinmonomericJC-1fluorescence, and hence loss of MMP occurred, with a decrease in Mcl-1 protein expression by 67% after 24 hrs despite an increase in Mcl-1 mRNA in MzChA-1 cells. In Vitro, silvestrol combined withothertherapeuticagentsresultedinadose-reductionindexof7.4-foldwithgemcitabine and 9.2-fold with cisplatin for 50% cytotoxicity. In Vivo treatment of tumor cell xenografts with either silvestrol, or diluent control was well tolerated with no significant weight loss or difference in weights between the groups. A dramatic antitumor effect was observed with a reduction in mean tumor volume of 43.2% by day 22 and 62.3% at day 29 in the treated group compared to the control group. The tumor weight at sacrifice (day 32) in silvestroltreated mice was 62.6% decreased compared to the control group (p = 0.02). Conclusion: Silvestrol is a novel therapeutic agent with highly potent In Vitro and In Vivo antitumor activity against cholangiocarcinoma. These studies highlight the use of both a structurally unique class of potential anticancer drugs (rocaglates)and a novel mechanism of drug action (targeting protein translation) in developing effective therapies for refractory cancers such as cholangiocarcinoma. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"clinicopathological significance hur expression gallbladder carcinoma special emphasis implications nuclear cytoplasmic expression gallbladder carcinoma gbc relatively rare disease pathogenesis less clarified human antigen r hur rna binding protein modulates expressions various cancer related proteins stabilizing regulating transcription corresponding messenger rna significance hur expression large cohort gbcs yet evaluated total 164 cases gbc selected immunostaining hur performed hur nuclear hur n expression hur cytoplasmic hur c expression evaluated using histochemical score results hur expression correlated various clinicopathological factors disease specific survival dss disease free survival dfs 161 patients follow data hur n overexpression strongly associated high histological grade p 0 001 vascular invasion p 0 001 high ki 67 labeling index p 0 001 hur c overexpression significantly related higher primary tumor status p 0 001 advanced tumor stage p 0 001 histological type p 0 006 high histological grade p 0 001 vascular perineurial invasion p 0 001 p 0 002 respectively tumor necrosis p 0 042 high ki 67 labeling index p 0 002 besides hur c overexpression also correlates hur n overexpression p 0 001 cyclin overexpression p 0 026 hur n overexpression correlated poor dfs p 0 0348 univariate analysis hur c overexpression strongly correlated worse dss dfs univariate p 0 0001 multivariate dss p 0 006 dfs p 0 001 analyses subcellular localization hur expression correlates different adverse phenotypes gbc besides hur c overexpression independent prognostic factor dismal dss dfs suggesting roles tumorigenesis carcinogenesis potential prognostic marker gbc pubmed","probabilities":0.8684211,"Title":"Clinicopathological significance of HuR expression in gallbladder carcinoma: with special emphasis on the implications of its nuclear and cytoplasmic expression","Abstract":"Gallbladder carcinoma (GBC) is a relatively rare disease which pathogenesis is less clarified. Human antigen R (HuR), a RNA-binding protein, modulates the expressions of various cancer-related proteins by stabilizing or regulating the transcription of the corresponding messenger RNA. The significance of HuR expression in a large cohort with GBCs is yet to be evaluated. In total, 164 cases of GBC were selected, and immunostaining for HuR was performed. HuR nuclear (HuR-N) expression and HuR cytoplasmic (HuR-C) expression were evaluated by using a histochemical score. The results of HuR expression were correlated with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS) in 161 patients with follow-up data. HuR-N overexpression was strongly associated with high histological grade (p = 0.001), vascular invasion (p < 0.001), and high Ki-67 labeling index (p < 0.001). HuR-C overexpression was significantly related to higher primary tumor status (p < 0.001), advanced tumor stage (p < 0.001), histological type (p = 0.006), high histological grade (p < 0.001), vascular and perineurial invasion (p < 0.001 and p = 0.002, respectively), tumor necrosis (p = 0.042), and high Ki-67 labeling index (p = 0.002). Besides, HuR-C overexpression also correlates with HuR-N overexpression (p < 0.001) and cyclin A overexpression (p = 0.026). HuR-N overexpression correlated with poor DFS (p = 0.0348) in univariate analysis, but HuR-C overexpression strongly correlated with a worse DSS and DFS in both univariate (both p < 0.0001) and multivariate (DSS, p = 0.006; DFS, p = 0.001) analyses. Subcellular localization of HuR expression correlates with different adverse phenotypes of GBC. Besides, HuR-C overexpression is an independent prognostic factor for dismal DSS and DFS, suggesting its roles in tumorigenesis or carcinogenesis and as a potential prognostic marker of GBC.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological significance of HuR expression in gallbladder carcinoma: with special emphasis on the implications of its nuclear and cytoplasmic expression Gallbladder carcinoma (GBC) is a relatively rare disease which pathogenesis is less clarified. Human antigen R (HuR), a RNA-binding protein, modulates the expressions of various cancer-related proteins by stabilizing or regulating the transcription of the corresponding messenger RNA. The significance of HuR expression in a large cohort with GBCs is yet to be evaluated. In total, 164 cases of GBC were selected, and immunostaining for HuR was performed. HuR nuclear (HuR-N) expression and HuR cytoplasmic (HuR-C) expression were evaluated by using a histochemical score. The results of HuR expression were correlated with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS) in 161 patients with follow-up data. HuR-N overexpression was strongly associated with high histological grade (p = 0.001), vascular invasion (p < 0.001), and high Ki-67 labeling index (p < 0.001). HuR-C overexpression was significantly related to higher primary tumor status (p < 0.001), advanced tumor stage (p < 0.001), histological type (p = 0.006), high histological grade (p < 0.001), vascular and perineurial invasion (p < 0.001 and p = 0.002, respectively), tumor necrosis (p = 0.042), and high Ki-67 labeling index (p = 0.002). Besides, HuR-C overexpression also correlates with HuR-N overexpression (p < 0.001) and cyclin A overexpression (p = 0.026). HuR-N overexpression correlated with poor DFS (p = 0.0348) in univariate analysis, but HuR-C overexpression strongly correlated with a worse DSS and DFS in both univariate (both p < 0.0001) and multivariate (DSS, p = 0.006; DFS, p = 0.001) analyses. Subcellular localization of HuR expression correlates with different adverse phenotypes of GBC. Besides, HuR-C overexpression is an independent prognostic factor for dismal DSS and DFS, suggesting its roles in tumorigenesis or carcinogenesis and as a potential prognostic marker of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"evaluation anticancer potential thai medicinal herb extracts cholangiocarcinoma cell lines although cholangiocarcinoma cca low incidence globally extremely high northeast thailand lack early detection measures effective therapeutic drugs major problem poor prognosis cca patients based regional knowledge advantageous search effective natural phyto products treatment cca cardiospermum halicacabum l gomphrena celosioides mart scoparia dulcis l well known medicinal herbs asian countries selected investigation inhibitory effects cca cells three different ethanolic extracts dulcis l extract showed inhibitory effects cell growth cca cell lines kku 100 kku 213 percentages 56 06 74 76 respectively compared untreated group treatment 250 g ml extracts 72 hrs 400 500 g ml extracts inhibitory effect kku 213 indicated significant increase bax bcl 2 ratio cell membrane permeability moreover metabolic profiling based screening employed current study revealed significant positive association lignin compound decrease cca cell viability study suggests first time esd ability inhibit cca cell growth induction apoptosis stn","probabilities":0.9467213,"Title":"Evaluation Of Anticancer Potential Of Thai Medicinal Herb Extracts Against Cholangiocarcinoma Cell Lines","Abstract":"Although cholangiocarcinoma (CCA) has a low incidence globally, this is extremely high in Northeast Thailand. The lack of both early detection measures and effective therapeutic drugs is the major problem for the poor prognosis of CCA patients. Based on regional knowledge, it would be advantageous to search for effective natural phyto-products for the treatment of CCA. Cardiospermum halicacabum L., Gomphrena celosioides Mart. and Scoparia dulcis L., very well-known medicinal herbs in Asian countries, were selected for the investigation of inhibitory effects on CCA cells. Of the three different ethanolic extracts, S. dulcis L extract showed most inhibitory effects on cell growth of CCA cell lines KKU-100 and KKU-213, at percentages of 56.06 and 74.76, respectively, compared to the untreated group after treatment with 250 μg/mL of extracts for 72 hrs. At 400 and 500 μg/mL of the extracts, the inhibitory effect of KKU-213 was indicated by a significant increase in the BAX/Bcl-2 ratio and cell membrane permeability. Moreover, metabolic profiling-based screening employed in the current study revealed a significant positive association between the lignin compound and a decrease in CCA cell viability. Our study suggests, for the first time, that ESD has the ability to inhibit CCA cell growth through the induction of apoptosis.","Source":"STN","category":"ANIMAL","training_data":"Evaluation Of Anticancer Potential Of Thai Medicinal Herb Extracts Against Cholangiocarcinoma Cell Lines Although cholangiocarcinoma (CCA) has a low incidence globally, this is extremely high in Northeast Thailand. The lack of both early detection measures and effective therapeutic drugs is the major problem for the poor prognosis of CCA patients. Based on regional knowledge, it would be advantageous to search for effective natural phyto-products for the treatment of CCA. Cardiospermum halicacabum L., Gomphrena celosioides Mart. and Scoparia dulcis L., very well-known medicinal herbs in Asian countries, were selected for the investigation of inhibitory effects on CCA cells. Of the three different ethanolic extracts, S. dulcis L extract showed most inhibitory effects on cell growth of CCA cell lines KKU-100 and KKU-213, at percentages of 56.06 and 74.76, respectively, compared to the untreated group after treatment with 250 μg/mL of extracts for 72 hrs. At 400 and 500 μg/mL of the extracts, the inhibitory effect of KKU-213 was indicated by a significant increase in the BAX/Bcl-2 ratio and cell membrane permeability. Moreover, metabolic profiling-based screening employed in the current study revealed a significant positive association between the lignin compound and a decrease in CCA cell viability. Our study suggests, for the first time, that ESD has the ability to inhibit CCA cell growth through the induction of apoptosis. STN","prediction_labels":"ANIMAL"},{"cleaned":"evaluation uicc tnm jsbs staging systems surgical patients extrahepatic cholangiocarcinoma aim two staging systems exist classify extrahepatic cholangiocarcinoma ehc tnm staging international union cancer uicc classification system japanese society biliary surgery jsbs study sought evaluate utility two staging systems method one hundred twenty eight consecutive patients underwent surgical resection retrospectively classified appropriate stages using uicc tnm jsbs systems also compared distribution survival curves respective stages results although uicc tnm staging system divided patients seven categories 106 128 patients 82 8 fell three stages stages ia iia iib contrast patients relatively evenly divided across five categories jsbs staging survival curve uicc tnm stage iib similar stage iv stages iia iii survival rates stages iib iv significantly lower stages according jsbs staging system significant differences stages iii iva ivb ii iva ivb iii iva ivb conclusions patients underwent surgical resection evenly divided across uicc tnm staging categories comparison jsbs staging stratification survival ability better using jsbs staging comparison uicc tnm system better understanding distribution patient classified stage stratification ability survival two staging system may help surgeons assess patients ehc pubmed","probabilities":0.9799733,"Title":"Evaluation of UICC-TNM and JSBS staging systems for surgical patients with extrahepatic cholangiocarcinoma","Abstract":"AIM: Two staging systems exist to classify extrahepatic cholangiocarcinoma (EHC), the TNM staging of the International Union Against Cancer (UICC) and the classification system of the Japanese Society of Biliary Surgery (JSBS). This study sought to evaluate the utility of these two staging systems. METHOD: One hundred and twenty eight consecutive patients who underwent surgical resection were retrospectively classified into the appropriate stages using the UICC-TNM and JSBS systems. We also compared the distribution and survival curves of respective stages. RESULTS: Although the UICC-TNM staging system divided patients into seven categories, 106 of 128 patients (82.8%) fell into three stages (stages IA, IIA, or IIB). In contrast, patients were relatively evenly divided across the five categories in JSBS staging. The survival curve of UICC-TNM stage IIB was more similar to stage IV than stages IIA or III; survival rates for stages IIB and IV were significantly lower than the other stages. According to the JSBS staging system, there were significant differences between stages I and III, IVA and IVB, and II and IVA/IVB, and III and IVA/IVB. CONCLUSIONS: Patients who underwent surgical resection were not evenly divided across UICC-TNM staging categories in comparison to JSBS staging. Stratification of survival ability was better when using the JSBS staging in comparison to the UICC-TNM system. The better understanding about distribution of patient classified by stage and stratification ability of survival of these two staging system may help surgeons assess the patients with EHC.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of UICC-TNM and JSBS staging systems for surgical patients with extrahepatic cholangiocarcinoma AIM: Two staging systems exist to classify extrahepatic cholangiocarcinoma (EHC), the TNM staging of the International Union Against Cancer (UICC) and the classification system of the Japanese Society of Biliary Surgery (JSBS). This study sought to evaluate the utility of these two staging systems. METHOD: One hundred and twenty eight consecutive patients who underwent surgical resection were retrospectively classified into the appropriate stages using the UICC-TNM and JSBS systems. We also compared the distribution and survival curves of respective stages. RESULTS: Although the UICC-TNM staging system divided patients into seven categories, 106 of 128 patients (82.8%) fell into three stages (stages IA, IIA, or IIB). In contrast, patients were relatively evenly divided across the five categories in JSBS staging. The survival curve of UICC-TNM stage IIB was more similar to stage IV than stages IIA or III; survival rates for stages IIB and IV were significantly lower than the other stages. According to the JSBS staging system, there were significant differences between stages I and III, IVA and IVB, and II and IVA/IVB, and III and IVA/IVB. CONCLUSIONS: Patients who underwent surgical resection were not evenly divided across UICC-TNM staging categories in comparison to JSBS staging. Stratification of survival ability was better when using the JSBS staging in comparison to the UICC-TNM system. The better understanding about distribution of patient classified by stage and stratification ability of survival of these two staging system may help surgeons assess the patients with EHC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression significance cox 2 ki 67 hepatolithiasis bile duct carcinoma background induced enzyme cox 2 expression elevated stimuli inflammatory mediator growth factor product ki 67 cell cycle related proliferative antigen reflects tissue proliferative activity study analyzed expressional profile cyclooxygenase 2 cox 2 ki 67 hepatolithiasis bile duct carcinoma tissues attempt provide evidence diagnosis prognosis prediction disease material methods cohort tissue samples hepatolithiasis bile duct carcinoma n 47 patients analyzed using immunohistochemical ihc staining method expression cox 2 ki 67 parallel hepatolithiasis n 44 normal bile duct tissues n 30 relationship expression pattern cox 2 ki 67 pathological conditions also analyzed addition correlation positive expression hepatolithiasis samples results positive expression rate cox 2 ki 67 bile duct carcinoma 76 6 80 9 respectively significantly higher hepatolithiasis group also higher control group expression cox 2 ki 67 closely related tnm staging lymph node metastasis differentiation stage also correlated mortality rate patients conclusions cox 2 ki 67 abundantly expressed hepatolithiasis bile duct carcinoma tissues may play important role disease occurrence progression metastasis pubmed","probabilities":0.962963,"Title":"Expression and Significance of COX-2 and Ki-67 in Hepatolithiasis with Bile Duct Carcinoma","Abstract":"BACKGROUND: As an induced enzyme, COX-2 expression is elevated under stimuli from inflammatory mediator or growth factor product. Ki-67, a cell cycle-related proliferative antigen, reflects the tissue proliferative activity. This study analyzed the expressional profile of cyclooxygenase-2 (COX-2) and Ki-67 in hepatolithiasis and bile duct carcinoma tissues, in an attempt to provide evidence for diagnosis and prognosis prediction of disease. MATERIAL AND METHODS: A cohort of tissue samples from hepatolithiasis with bile duct carcinoma (N=47) patients were analyzed using immunohistochemical (IHC) staining method for the expression of COX-2 and Ki-67, in parallel with hepatolithiasis (N=44) and normal bile duct tissues (N=30). The relationship between expression pattern of COX-2 and Ki-67 and pathological conditions was also analyzed, in addition to the correlation with positive expression in hepatolithiasis samples. RESULTS: The positive expression rate of COX-2 and Ki-67 in bile duct carcinoma was 76.6% and 80.9%, respectively, and was significantly higher than those in the hepatolithiasis group, which was also higher than the control group. Expression of both COX-2 and Ki-67 is closely related to TNM staging, lymph node metastasis, and differentiation stage. They were also correlated with the mortality rate of patients. CONCLUSIONS: Both COX-2 and Ki-67 are abundantly expressed in hepatolithiasis and bile duct carcinoma tissues and may play an important role in the disease occurrence, progression, and metastasis.","Source":"PubMed","category":"HUMAN","training_data":"Expression and Significance of COX-2 and Ki-67 in Hepatolithiasis with Bile Duct Carcinoma BACKGROUND: As an induced enzyme, COX-2 expression is elevated under stimuli from inflammatory mediator or growth factor product. Ki-67, a cell cycle-related proliferative antigen, reflects the tissue proliferative activity. This study analyzed the expressional profile of cyclooxygenase-2 (COX-2) and Ki-67 in hepatolithiasis and bile duct carcinoma tissues, in an attempt to provide evidence for diagnosis and prognosis prediction of disease. MATERIAL AND METHODS: A cohort of tissue samples from hepatolithiasis with bile duct carcinoma (N=47) patients were analyzed using immunohistochemical (IHC) staining method for the expression of COX-2 and Ki-67, in parallel with hepatolithiasis (N=44) and normal bile duct tissues (N=30). The relationship between expression pattern of COX-2 and Ki-67 and pathological conditions was also analyzed, in addition to the correlation with positive expression in hepatolithiasis samples. RESULTS: The positive expression rate of COX-2 and Ki-67 in bile duct carcinoma was 76.6% and 80.9%, respectively, and was significantly higher than those in the hepatolithiasis group, which was also higher than the control group. Expression of both COX-2 and Ki-67 is closely related to TNM staging, lymph node metastasis, and differentiation stage. They were also correlated with the mortality rate of patients. CONCLUSIONS: Both COX-2 and Ki-67 are abundantly expressed in hepatolithiasis and bile duct carcinoma tissues and may play an important role in the disease occurrence, progression, and metastasis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"first repeat liver resection primary recurrent intrahepatic cholangiocarcinoma background recurrence resection intrahepatic cholangiocarcinoma icc remains common present study sought evaluate risk factors recurrence results repeat liver resection rlr recurrent icc methods 1997 2012 clinical data outcomes 125 consecutive patients undergoing liver resection icc retrospectively analyzed results rate r0 resection 89 n 110 overall median survival 35 months 1 3 5 year actuarial survival rates 80 48 28 respectively recurrence occurred 76 patients 63 5 intrahepatic 39 patients 51 tumor size greater 5 cm identified independent risk factor recurrence p 0001 rlr recurrent icc feasible 10 patients 25 median survival recurrence 25 months 16 76 conclusions tumor size 5 cm represents independent risk factor recurrence resection icc rlr case recurrent icc feasible associated longer overall survival pubmed","probabilities":0.9799733,"Title":"First and repeat liver resection for primary and recurrent intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Recurrence after resection of intrahepatic cholangiocarcinoma (ICC) remains common. The present study sought to evaluate risk factors for recurrence and the results of repeat liver resection (RLR) for recurrent ICC. METHODS: Between 1997 and 2012, clinical data and outcomes of 125 consecutive patients undergoing liver resection for ICC were retrospectively analyzed. RESULTS: The rate of R0 resection was 89% (n = 110). Overall median survival was 35 months, and 1-, 3-, and 5-year actuarial survival rates were 80%, 48%, and 28%, respectively. Recurrence occurred in 76 patients (63.5%) and was intrahepatic only for 39 patients (51%). Tumor size greater than 5 cm was identified as an independent risk factor for recurrence (P ≤ .0001). RLR for recurrent ICC was feasible in 10 patients (25%) with a median survival after recurrence of 25 months (16 to 76). CONCLUSIONS: Tumor size more than 5 cm represents an independent risk factor for recurrence after resection of ICC. RLR in case of recurrent ICC, when feasible, is associated with longer overall survival.","Source":"PubMed","category":"HUMAN","training_data":"First and repeat liver resection for primary and recurrent intrahepatic cholangiocarcinoma BACKGROUND: Recurrence after resection of intrahepatic cholangiocarcinoma (ICC) remains common. The present study sought to evaluate risk factors for recurrence and the results of repeat liver resection (RLR) for recurrent ICC. METHODS: Between 1997 and 2012, clinical data and outcomes of 125 consecutive patients undergoing liver resection for ICC were retrospectively analyzed. RESULTS: The rate of R0 resection was 89% (n = 110). Overall median survival was 35 months, and 1-, 3-, and 5-year actuarial survival rates were 80%, 48%, and 28%, respectively. Recurrence occurred in 76 patients (63.5%) and was intrahepatic only for 39 patients (51%). Tumor size greater than 5 cm was identified as an independent risk factor for recurrence (P ≤ .0001). RLR for recurrent ICC was feasible in 10 patients (25%) with a median survival after recurrence of 25 months (16 to 76). CONCLUSIONS: Tumor size more than 5 cm represents an independent risk factor for recurrence after resection of ICC. RLR in case of recurrent ICC, when feasible, is associated with longer overall survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical presentation risk factors staging systems cholangiocarcinoma cholangiocarcinoma cca second common primary liver tumour intra hepatic cca develops within liver parenchyma extrahepatic cca involves biliary tree within hepatoduodenal ligament hilar cca also called klatskin tumour cca incidence increased worldwide last years also geographic differences focus asian countries known risk factors primary sclerosing cholangitis psc hepatolithiasis caroli disease hepatitis b c infection liver flukes cirrhosis diabetes obesity alcohol consumption probably tobacco smoking patients early cca little discomfort later show episodes jaundice non specific tumour symptoms staging disease different classifications available consider various factors like tumour size location regional lymph nodes metastasis vascular involvement tumour marker pubmed","probabilities":0.9799733,"Title":"Clinical presentation, risk factors and staging systems of cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is the second most common primary liver tumour. Intra-hepatic CCA develops within the liver parenchyma while extrahepatic CCA involves the biliary tree within the hepatoduodenal ligament. Hilar CCA are also called Klatskin tumour. The CCA incidence has increased worldwide over the last years, but there are also geographic differences, with focus in Asian countries. Known risk factors are primary sclerosing cholangitis (PSC), hepatolithiasis, Caroli's disease, hepatitis B and C infection, liver flukes, cirrhosis, diabetes, obesity, alcohol consumption and probably tobacco smoking. Patients with early CCA have only little discomfort, but can later show episodes with jaundice and other non-specific tumour symptoms. For the staging of the disease different classifications are available, which consider various factors like tumour size, location, regional lymph nodes, metastasis, vascular involvement and tumour marker.","Source":"PubMed","category":"HUMAN","training_data":"Clinical presentation, risk factors and staging systems of cholangiocarcinoma Cholangiocarcinoma (CCA) is the second most common primary liver tumour. Intra-hepatic CCA develops within the liver parenchyma while extrahepatic CCA involves the biliary tree within the hepatoduodenal ligament. Hilar CCA are also called Klatskin tumour. The CCA incidence has increased worldwide over the last years, but there are also geographic differences, with focus in Asian countries. Known risk factors are primary sclerosing cholangitis (PSC), hepatolithiasis, Caroli's disease, hepatitis B and C infection, liver flukes, cirrhosis, diabetes, obesity, alcohol consumption and probably tobacco smoking. Patients with early CCA have only little discomfort, but can later show episodes with jaundice and other non-specific tumour symptoms. For the staging of the disease different classifications are available, which consider various factors like tumour size, location, regional lymph nodes, metastasis, vascular involvement and tumour marker. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value tumor infiltrating lymphocytes tils expression pd l1 cholangiocarcinoma cholangiocarcinoma malignancy arising biliary tract epithelial cells poor prognosis tumor infiltrating lymphocytes til programmed cell death receptor ligand 1 pd l1 prognostic impact various solid tumors aimed investigate tils pd l1 expression clinical relevance cholangiocarcinoma tumor samples 44 patients resected histologically verified extrahepatic cholangiocarcinoma evaluated cd8 cd45ro pd l1 expression correlations clinicopathological data survival data analyzed total 44 extrahepatic cholangiocarcinoma tissues evaluated cd8 tumor infiltrating lymphocytes til observed 30 68 tumors among 14 cd8 cd45ro tils pd l1 expressed cancer cells 10 22 7 tumors 34 evaluable extrahepatic cholangiocarciniomas presence cd8 tils cd8 cd45ro tils associated clinical staging tumor differentiation extrahepatic cholangiocarcinoma cd8 cd45ro tils longer overall survival os univariate p 0 013 multivariate p 0 012 analysis neither cd8 til pd l1 expression cancer cells correlated significantly os results add understanding clinical features associated cd8 tils pd l1 expression extrahepatic cholangiocarcinoma support potential rationale using pd 1 blockade immunotherapy cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Prognostic Value Of Tumor-Infiltrating Lymphocytes (Tils) And Expression Of Pd-L1 In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma is a malignancy arising from the biliary tract epithelial cells with poor prognosis. Tumor infiltrating lymphocytes (TIL)s and programmed cell death receptor ligand 1 (PD-L1) have a prognostic impact in various solid tumors. We aimed to investigate TILs and PD-L1 expression and their clinical relevance in cholangiocarcinoma. Tumor samples from 44 patients with resected and histologically verified extrahepatic cholangiocarcinoma were evaluated for CD8, CD45RO and PD-L1 expression, and their correlations with clinicopathological data and survival data were analyzed. Total 44 extrahepatic cholangiocarcinoma tissues were evaluated. CD8+ tumor infiltrating lymphocytes (TIL)s were observed in 30 (68%) tumors. Among them, 14 had CD8+CD45RO+ TILs. PD-L1 was expressed on cancer cells in 10 (22.7%) tumors in 34 evaluable extrahepatic cholangiocarciniomas. The presence of CD8+ TILs or CD8+CD45RO+ TILs was not associated with clinical staging or tumor differentiation. Extrahepatic cholangiocarcinoma with CD8+CD45RO+ TILs had longer overall survival (OS) on univariate (P = 0.013) and multivariate (P = 0.012) analysis. Neither CD8+TIL nor PD-L1 expression on cancer cells correlated significantly with OS. These results add to the understanding of the clinical features associated with CD8 TILs and PD-L1 expression in extrahepatic cholangiocarcinoma, and they support the potential rationale of using PD-1 blockade immunotherapy in cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Prognostic Value Of Tumor-Infiltrating Lymphocytes (Tils) And Expression Of Pd-L1 In Cholangiocarcinoma Cholangiocarcinoma is a malignancy arising from the biliary tract epithelial cells with poor prognosis. Tumor infiltrating lymphocytes (TIL)s and programmed cell death receptor ligand 1 (PD-L1) have a prognostic impact in various solid tumors. We aimed to investigate TILs and PD-L1 expression and their clinical relevance in cholangiocarcinoma. Tumor samples from 44 patients with resected and histologically verified extrahepatic cholangiocarcinoma were evaluated for CD8, CD45RO and PD-L1 expression, and their correlations with clinicopathological data and survival data were analyzed. Total 44 extrahepatic cholangiocarcinoma tissues were evaluated. CD8+ tumor infiltrating lymphocytes (TIL)s were observed in 30 (68%) tumors. Among them, 14 had CD8+CD45RO+ TILs. PD-L1 was expressed on cancer cells in 10 (22.7%) tumors in 34 evaluable extrahepatic cholangiocarciniomas. The presence of CD8+ TILs or CD8+CD45RO+ TILs was not associated with clinical staging or tumor differentiation. Extrahepatic cholangiocarcinoma with CD8+CD45RO+ TILs had longer overall survival (OS) on univariate (P = 0.013) and multivariate (P = 0.012) analysis. Neither CD8+TIL nor PD-L1 expression on cancer cells correlated significantly with OS. These results add to the understanding of the clinical features associated with CD8 TILs and PD-L1 expression in extrahepatic cholangiocarcinoma, and they support the potential rationale of using PD-1 blockade immunotherapy in cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"biologic behavior gallbladder high grade dysplasia long term survival analysis 125 cases elucidates mostly curable disease marker biliary tract cancer risk patients background estimated 20 thousand gallbladder dysplasias encountered us annually incidence much higher high gallbladder cancer risk regions meantime virtually information biological behavior gallbladder high grade dysplasia carcinoma situ hgd cis design pathologic ndings clinical outcome 125 unequivocal examples gallbladder hgd cis analyzed results female male 3 5 mean age 56 ninety eight cases undergone total sampling gallbladder per protocol devised roa et al rev chil cirugia 57 436 442 remaining cases sampled average 6 blocks range 1 12 median follow 152 months 1 3 5 10 year survival rates 96 93 90 86 respectively twenty three patients died median follow 88 months 1 perioperative mortality five patients died 20 38 44 44 46 months appeared progression cancer gallbladder biliary tract four 4 5 gallbladders incompletely sampled average 7 blocks presumably representing missed invasion also 2 hgd cis cystic duct margin four patients died cancers 1 colon 8 months 1 esophagus 16 months 1 plasmacytoma 88 months 1 cervical 200 mos four died biliary tract cancer around 10 years 104 109 134 138 months cystic duct margin negative 4 nine deaths related medical conditions pneumonia 5 cardiovascular 3 sepsis 1 median follow 127 months conclusions possibility invasive carcinoma excluded total sampling vast majority gallbladder hgd cis cases cured cholecystectomy thus total sampling gallbladders hgd cis crucial small subset patients develop biliary tract cancers around 10 years possibly related eld effect defect phenomenon therefore long term follow patients warranted google scholar","probabilities":0.9799733,"Title":"Biologic Behavior Of Gallbladder High-Grade Dysplasia: A Long-Term Survival Analysis Of 125 Cases Elucidates A Mostly Curable Disease Which Is A Marker Of Biliary Tract Cancer Risk In Some Patients","Abstract":"Background: Estimated some 20-thousand gallbladder dysplasias are encountered in the US annually, and the incidence is much higher in high-gallbladder cancer risk regions. In the meantime, there is virtually no information on biological behavior of gallbladder high-grade dysplasia/carcinoma in-situ (HGD/CIS). Design: The pathologic fi ndings and clinical outcome in 125 unequivocal examples of gallbladder HGD/CIS were analyzed. Results: Female/Male was 3.5, mean age was 56. Ninety-eight cases had undergone total sampling of the gallbladder as per the protocol devised by Roa et al (Rev Chil Cirugia 57:436–442), and the remaining cases had been sampled in average of 6 blocks (range, 1-12). In a median follow-up 152 months, 1-, 3-, 5- and 10-year survival rates were 96%, 93%, 90%, and 86%, respectively. Twenty-three patients died at a median follow-up of 88 months, 1 was perioperative mortality. Five patients died at 20, 38, 44, 44 and 46 months of what appeared to be progression of cancer in the gallbladder/ biliary tract. Four 4 of these 5 were gallbladders that were incompletely sampled in average of 7 blocks, presumably representing missed invasion, and also 2 had HGD/ CIS at the cystic duct margin. Four patients died of other cancers; 1 colon at 8 months, 1 esophagus at 16 months, 1 plasmacytoma at 88 months, 1 cervical at 200 mos. Four died of a biliary tract cancer at around 10 years (104,109, 134 and 138 months) and cystic duct margin was negative in all 4. Nine deaths were related to medical conditions (pneumonia in 5, cardiovascular in 3, sepsis in 1) at a median follow-up of 127 months. Conclusions: If the possibility of invasive carcinoma is excluded by total sampling, the vast majority of all gallbladder HGD/CIS cases are cured by cholecystectomy. Thus, total sampling of gallbladders with HGD/CIS is crucial. A small subset of patients develop biliary tract cancers at around 10 years, possibly related to fi eld-effect/defect phenomenon. Therefore, long term follow-up of these patients is warranted.","Source":"Google Scholar","category":"ANIMAL","training_data":"Biologic Behavior Of Gallbladder High-Grade Dysplasia: A Long-Term Survival Analysis Of 125 Cases Elucidates A Mostly Curable Disease Which Is A Marker Of Biliary Tract Cancer Risk In Some Patients Background: Estimated some 20-thousand gallbladder dysplasias are encountered in the US annually, and the incidence is much higher in high-gallbladder cancer risk regions. In the meantime, there is virtually no information on biological behavior of gallbladder high-grade dysplasia/carcinoma in-situ (HGD/CIS). Design: The pathologic fi ndings and clinical outcome in 125 unequivocal examples of gallbladder HGD/CIS were analyzed. Results: Female/Male was 3.5, mean age was 56. Ninety-eight cases had undergone total sampling of the gallbladder as per the protocol devised by Roa et al (Rev Chil Cirugia 57:436–442), and the remaining cases had been sampled in average of 6 blocks (range, 1-12). In a median follow-up 152 months, 1-, 3-, 5- and 10-year survival rates were 96%, 93%, 90%, and 86%, respectively. Twenty-three patients died at a median follow-up of 88 months, 1 was perioperative mortality. Five patients died at 20, 38, 44, 44 and 46 months of what appeared to be progression of cancer in the gallbladder/ biliary tract. Four 4 of these 5 were gallbladders that were incompletely sampled in average of 7 blocks, presumably representing missed invasion, and also 2 had HGD/ CIS at the cystic duct margin. Four patients died of other cancers; 1 colon at 8 months, 1 esophagus at 16 months, 1 plasmacytoma at 88 months, 1 cervical at 200 mos. Four died of a biliary tract cancer at around 10 years (104,109, 134 and 138 months) and cystic duct margin was negative in all 4. Nine deaths were related to medical conditions (pneumonia in 5, cardiovascular in 3, sepsis in 1) at a median follow-up of 127 months. Conclusions: If the possibility of invasive carcinoma is excluded by total sampling, the vast majority of all gallbladder HGD/CIS cases are cured by cholecystectomy. Thus, total sampling of gallbladders with HGD/CIS is crucial. A small subset of patients develop biliary tract cancers at around 10 years, possibly related to fi eld-effect/defect phenomenon. Therefore, long term follow-up of these patients is warranted. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic role bap 1 pbrm 1 expression intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc universally poor outcome mainly due late clinical presentation identification specific biomarkers development effective treatment still urgently required mutations pbrm 1 bap 1 genes expression s100p related survival icc mir 31 seems also play important regulatory functions icc directly regulates bap 1 expression lung cancer study tissue expression bap 1 pbrm 1 s100p mir 31 investigated icc correlated clinical pathological features sixty one consecutive patients underwent curative hepatic resection icc enrolled none received therapy prior surgery immunostaining bap 1 pbrm 1 s100p situ hybridization mir 31 performed using tissue microarray slides strong retained expression bap 1 pbrm 1 associated reduced overall p 0 04 p 0 002 respectively disease free survival p 0 05 p 0 02 respectively overexpression s100p related reduced overall survival p 0 005 multivariate analyses identified presence perineural invasion retained pbrm 1 expression independent predictors worse overall p 0 02 hazard ratio hr 2 25 1 16 4 39 p 0 001 hr 3 13 1 56 6 28 respectively disease free survivals p 0 03 hr 2 43 1 09 5 4 p 0 03 hr 2 51 1 11 5 67 respectively overexpression s100p predictive worse overall survival p 0 02 hr 1 66 1 08 2 55 high levels mir 31 significantly associated low expression bap 1 protein p 0 03 icc retained expression bap 1 pbrm 1 overexpression s100p related poor prognosis pubmed","probabilities":0.7966102,"Title":"Prognostic role of BAP-1 and PBRM-1 expression in intrahepatic cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) has universally poor outcome, mainly due to its late clinical presentation. Identification of specific biomarkers and development of effective treatment are still urgently required. Mutations in PBRM-1 and BAP-1 genes, and the expression of S100P have been related to survival in ICC. miR-31 seems also to play important regulatory functions in ICC and it directly regulates BAP-1 expression in lung cancer. In this study, tissue expression of BAP-1, PBRM-1, S100P, and miR-31 was investigated in ICC and correlated with clinical-pathological features. Sixty-one consecutive patients who underwent curative hepatic resection for ICC were enrolled. None received any therapy prior to surgery. Immunostaining for BAP-1, PBRM-1, and S100P, and in situ hybridization for miR-31 were performed, using tissue microarray slides. A strong retained expression of BAP-1 and PBRM-1 was associated with a reduced overall (p = 0.04 and p = 0.002, respectively) and disease-free survival (p = 0.05 and p = 0.02, respectively). An overexpression of S100P was related to a reduced overall survival (p = 0.005). The multivariate analyses identified the presence of perineural invasion and the retained PBRM-1 expression as independent predictors of worse overall [p = 0.02, hazard ratio (HR) = 2.25 (1.16-4.39) and p = 0.001, HR = 3.13 (1.56-6.28), respectively] and disease-free survivals [p = 0.03, HR = 2.43 (1.09-5.4) and p = 0.03, HR = 2.51 (1.11-5.67), respectively]. An overexpression of S100P was predictive of a worse overall survival [p = 0.02, HR = 1.66 (1.08-2.55)]. High levels of miR-31 were significantly associated to a low expression of BAP-1 protein (p = 0.03). In ICC, a retained expression of BAP-1 and PBRM-1, and an overexpression of S100P are related to a poor prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic role of BAP-1 and PBRM-1 expression in intrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) has universally poor outcome, mainly due to its late clinical presentation. Identification of specific biomarkers and development of effective treatment are still urgently required. Mutations in PBRM-1 and BAP-1 genes, and the expression of S100P have been related to survival in ICC. miR-31 seems also to play important regulatory functions in ICC and it directly regulates BAP-1 expression in lung cancer. In this study, tissue expression of BAP-1, PBRM-1, S100P, and miR-31 was investigated in ICC and correlated with clinical-pathological features. Sixty-one consecutive patients who underwent curative hepatic resection for ICC were enrolled. None received any therapy prior to surgery. Immunostaining for BAP-1, PBRM-1, and S100P, and in situ hybridization for miR-31 were performed, using tissue microarray slides. A strong retained expression of BAP-1 and PBRM-1 was associated with a reduced overall (p = 0.04 and p = 0.002, respectively) and disease-free survival (p = 0.05 and p = 0.02, respectively). An overexpression of S100P was related to a reduced overall survival (p = 0.005). The multivariate analyses identified the presence of perineural invasion and the retained PBRM-1 expression as independent predictors of worse overall [p = 0.02, hazard ratio (HR) = 2.25 (1.16-4.39) and p = 0.001, HR = 3.13 (1.56-6.28), respectively] and disease-free survivals [p = 0.03, HR = 2.43 (1.09-5.4) and p = 0.03, HR = 2.51 (1.11-5.67), respectively]. An overexpression of S100P was predictive of a worse overall survival [p = 0.02, HR = 1.66 (1.08-2.55)]. High levels of miR-31 were significantly associated to a low expression of BAP-1 protein (p = 0.03). In ICC, a retained expression of BAP-1 and PBRM-1, and an overexpression of S100P are related to a poor prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"complex spectrum forensic issues arising obesity increasing numbers obese morbidly obese individuals community direct effect forensic facilities addition install robust equipment handling large bodies quality autopsy examinations may reduced physical difficulties arise trying position bodies correctly normal examinations proceed accelerated putrefaction often added complication metabolic disturbances resulting obesity increase susceptibility range conditions associated sudden unexpected death surgery may increased complications rates number different malignancies including lymphoma leukemia melanoma multiple myeloma carcinomas esophagus stomach colon gallbladder thyroid prostate breast endometrium increased addition obese individuals higher rates diabetes mellitus sepsis unexpected collapse obese individual raise possibility wide range conditions many may difficult demonstrate autopsy individual normal body mass index although sudden cardiac death due cardiomegaly pulmonary thromboembolism ischemic heart disease may probable diagnosis unexpected collapse range possible underlying conditions extensive often determinable full postmortem examination pubmed","probabilities":0.9799733,"Title":"The complex spectrum of forensic issues arising from obesity","Abstract":"The increasing numbers of obese and morbidly obese individuals in the community are having a direct effect on forensic facilities. In addition to having to install more robust equipment for handling large bodies, the quality of autopsy examinations may be reduced by the physical difficulties that arise in trying to position bodies correctly so that normal examinations can proceed. Accelerated putrefaction is often an added complication. Metabolic disturbances resulting from obesity increase susceptibility to a range of conditions that are associated with sudden and unexpected death, and surgery may have increased complications. The rates of a number of different malignancies, including lymphoma, leukemia, melanoma and multiple myeloma, and carcinomas of the esophagus, stomach, colon, gallbladder, thyroid, prostate, breast and endometrium, are increased. In addition, obese individuals have higher rates of diabetes mellitus, and sepsis. The unexpected collapse of an obese individual should raise the possibility of a wide range of conditions, many of which may be more difficult to demonstrate at autopsy than in an individual with a normal body mass index. Although sudden cardiac death due to cardiomegaly, pulmonary thromboembolism, or ischemic heart disease may be the most probable diagnosis in an unexpected collapse, the range of possible underlying conditions is extensive and often only determinable after full postmortem examination.","Source":"PubMed","category":"HUMAN","training_data":"The complex spectrum of forensic issues arising from obesity The increasing numbers of obese and morbidly obese individuals in the community are having a direct effect on forensic facilities. In addition to having to install more robust equipment for handling large bodies, the quality of autopsy examinations may be reduced by the physical difficulties that arise in trying to position bodies correctly so that normal examinations can proceed. Accelerated putrefaction is often an added complication. Metabolic disturbances resulting from obesity increase susceptibility to a range of conditions that are associated with sudden and unexpected death, and surgery may have increased complications. The rates of a number of different malignancies, including lymphoma, leukemia, melanoma and multiple myeloma, and carcinomas of the esophagus, stomach, colon, gallbladder, thyroid, prostate, breast and endometrium, are increased. In addition, obese individuals have higher rates of diabetes mellitus, and sepsis. The unexpected collapse of an obese individual should raise the possibility of a wide range of conditions, many of which may be more difficult to demonstrate at autopsy than in an individual with a normal body mass index. Although sudden cardiac death due to cardiomegaly, pulmonary thromboembolism, or ischemic heart disease may be the most probable diagnosis in an unexpected collapse, the range of possible underlying conditions is extensive and often only determinable after full postmortem examination. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors survival patients advanced intrahepatic cholangiocarcinoma treated gemcitabine plus cisplatin first line treatment objectives intrahepatic cholangiocarcinoma icc rare type liver cancer clinically useful prognostic factors reported patients advanced icc present study aimed evaluate clinical prognostic factors patients advanced icc receiving gemcitabine plus cisplatin combination therapy gc standard first line chemotherapy methods retrospective analysis performed data patients icc treated institution march 2011 january 2016 used cox regression model estimated hazard ratios potential prognostic factors survival results 216 patients biliary tract cancer receiving gc first line chemotherapy extracted data 77 patients diagnosed icc received gc first line chemotherapy median overall survival 13 8 months 95 ci 8 9 18 6 multivariate analysis pretreatment serum lactate dehydrogenase hazard ratio hr 2 53 p 0 005 c reactive protein hr 3 06 p 0 001 carcinoembryonic antigen hr 2 39 p 0 03 levels significantly associated overall survival conclusions readily available clinical laboratory values reliably predicted prognosis icc patients receiving gc therapy validated studies results may provide useful tool individual patient risk evaluation design interpretation future trials google scholar","probabilities":0.9799733,"Title":"Prognostic Factors For Survival In Patients With Advanced Intrahepatic Cholangiocarcinoma Treated With Gemcitabine Plus Cisplatin As First Line Treatment","Abstract":"Objectives: Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. Methods: A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. Results: Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. Conclusions: Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Factors For Survival In Patients With Advanced Intrahepatic Cholangiocarcinoma Treated With Gemcitabine Plus Cisplatin As First Line Treatment Objectives: Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. Methods: A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. Results: Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. Conclusions: Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinical significances cancer stem cells markers patients intrahepatic cholangiocarcinoma underwent hepatectomy present study aimed elucidate relationship cancer stem cells markers cscs according cell adhesion molecule cd44 glioma associated oncogene homolog 1 gli1 expression clinicopathological factors prognosis 38 patients intrahepatic cholangiocarcinoma icc underwent hepatectomy cd44 gli1 expression examined immunohistochemical staining methods relationship tumor angiogenesis proliferation activity also analyzed positivity cd44 18 gli1 39 significant correlation expressions macroscopic findings cd44 expression periductal infiltration type icc significantly higher types p 0 01 type showed significantly worse survival hepatectomy positive expression gli1 significantly associated older age although expression neither cd44 gli1 significantly associated disease free survival positive expression cd44 gli1 led significantly lower 3 year disease free survival rate 0 p 0 05 respect 5 year overall survival hepatectomy expression cd44 gli1 significantly associated survival rate cscs might useful markers tumor free survival patients icc hepatectomy investigation larger series warranted pubmed","probabilities":0.962963,"Title":"Clinical significances of cancer stem cells markers in patients with intrahepatic cholangiocarcinoma who underwent hepatectomy","Abstract":"The present study aimed to elucidate the relationship between cancer stem cells markers (CSCs), according to cell adhesion molecule (CD44) and glioma-associated oncogene homolog-1 (GLI1) expression, and clinicopathological factors and prognosis in 38 patients with intrahepatic cholangiocarcinoma (ICC) who underwent hepatectomy. CD44 and GLI1 expression was examined by immunohistochemical staining methods. The relationship with tumor angiogenesis or proliferation activity was also analyzed. Positivity of CD44 was 18% and that of GLI1 was 39%, but there was no significant correlation between the expressions of both. On macroscopic findings, CD44 expression in the periductal infiltration-type of ICC was significantly higher than in other types (p<0.01), and this type showed significantly worse survival after hepatectomy. Positive expression of GLI1 was significantly associated with older age. Although expression of neither CD44 nor GLI1 was significantly associated with disease-free survival, positive expression of both CD44 and GLI1 led to a significantly lower 3-year disease-free survival rate (0%; p<0.05). With respect to 5-year overall survival after hepatectomy, expression of both CD44 and GLI1 was not significantly associated with survival rate. CSCs might be useful markers for tumor-free survival in patients with ICC after hepatectomy and further investigation in larger series is warranted.","Source":"PubMed","category":"HUMAN","training_data":"Clinical significances of cancer stem cells markers in patients with intrahepatic cholangiocarcinoma who underwent hepatectomy The present study aimed to elucidate the relationship between cancer stem cells markers (CSCs), according to cell adhesion molecule (CD44) and glioma-associated oncogene homolog-1 (GLI1) expression, and clinicopathological factors and prognosis in 38 patients with intrahepatic cholangiocarcinoma (ICC) who underwent hepatectomy. CD44 and GLI1 expression was examined by immunohistochemical staining methods. The relationship with tumor angiogenesis or proliferation activity was also analyzed. Positivity of CD44 was 18% and that of GLI1 was 39%, but there was no significant correlation between the expressions of both. On macroscopic findings, CD44 expression in the periductal infiltration-type of ICC was significantly higher than in other types (p<0.01), and this type showed significantly worse survival after hepatectomy. Positive expression of GLI1 was significantly associated with older age. Although expression of neither CD44 nor GLI1 was significantly associated with disease-free survival, positive expression of both CD44 and GLI1 led to a significantly lower 3-year disease-free survival rate (0%; p<0.05). With respect to 5-year overall survival after hepatectomy, expression of both CD44 and GLI1 was not significantly associated with survival rate. CSCs might be useful markers for tumor-free survival in patients with ICC after hepatectomy and further investigation in larger series is warranted. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression pten associated improved prognosis patients ampullary adenocarcinoma pancreaticoduodenectomy context phosphatase tensin homolog pten one frequently inactivated tumor suppressor genes sporadic cancers somatic mutations pten occur many tumors including gastrointestinal hepatobiliary tracts loss pten expression associated poor prognosis patients metastatic colonic adenocarcinoma gastroesophageal junction adenocarcinoma gastric adenocarcinoma pancreatic ductal adenocarcinoma objective study expression pten significance ampullary adenocarcinoma aa design constructed tissue microarrays using archival tissue 92 patients 55 males 37 females median age 63 years age range 37 87 years previously untreated aa underwent pancreaticoduodenectomy institution pten expression evaluated immunohistochemistry scored semiquantitatively based staining intensity percentage positive tumor cells correlated clinicopathologic features survival results 92 cases 23 25 0 pten negative loss pten expression correlated lymph node metastasis p 004 advanced american joint committee cancer ajcc stage p 02 higher frequency recurrence p 03 patients pten negative tumors shorter disease free survival dfs mean 89 0 20 8 months overall survival os mean 93 1 19 1 months pten positive tumors dfs mean 161 4 11 7 months p 01 os mean 175 4 11 0 months p 001 multivariate analyses pten expression prognostic factor dfs os independent ajcc stage lymph node status pathologic tumor pt stage differentiation conclusions loss pten expression associated poor dfs os patients aa curative surgery pten expression may used prognostic marker patients resected aa pubmed","probabilities":0.7966102,"Title":"The expression of PTEN is associated with improved prognosis in patients with ampullary adenocarcinoma after pancreaticoduodenectomy","Abstract":"CONTEXT: Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Somatic mutations of PTEN occur in many tumors including those of the gastrointestinal and hepatobiliary tracts. Loss of PTEN expression is associated with poor prognosis in patients with metastatic colonic adenocarcinoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma, and pancreatic ductal adenocarcinoma. OBJECTIVE: To study the expression of PTEN and its significance in ampullary adenocarcinoma (AA). DESIGN: We constructed tissue microarrays by using archival tissue from 92 patients (55 males, 37 females; median age, 63 years; age range, 37 to 87 years) with previously untreated AA who underwent pancreaticoduodenectomy at our institution. PTEN expression was evaluated by immunohistochemistry, scored semiquantitatively (based on staining intensity and percentage positive tumor cells), and correlated with clinicopathologic features and survival. RESULTS: Of 92 cases, 23 (25.0%) were PTEN negative. Loss of PTEN expression correlated with lymph node metastasis (P = .004), advanced American Joint Committee on Cancer (AJCC) stage (P = .02), and higher frequency of recurrence (P = .03). Patients with PTEN-negative tumors had shorter disease-free survival (DFS, mean: 89.0 ± 20.8 months) and overall survival (OS, mean: 93.1 ± 19.1 months) than those with PTEN-positive tumors (DFS, mean: 161.4 ± 11.7 months, P = .01; OS, mean: 175.4 ± 11.0 months, P = .001). In multivariate analyses, PTEN expression was a prognostic factor for both DFS and OS, independent of AJCC stage, lymph node status, pathologic tumor (pT) stage, and differentiation. CONCLUSIONS: Loss of PTEN expression is associated with poor DFS and OS in patients with AA after curative surgery. PTEN expression may be used as a prognostic marker for patients with resected AA.","Source":"PubMed","category":"HUMAN","training_data":"The expression of PTEN is associated with improved prognosis in patients with ampullary adenocarcinoma after pancreaticoduodenectomy CONTEXT: Phosphatase and tensin homolog (PTEN) is one of the most frequently inactivated tumor suppressor genes in sporadic cancers. Somatic mutations of PTEN occur in many tumors including those of the gastrointestinal and hepatobiliary tracts. Loss of PTEN expression is associated with poor prognosis in patients with metastatic colonic adenocarcinoma, gastroesophageal junction adenocarcinoma, gastric adenocarcinoma, and pancreatic ductal adenocarcinoma. OBJECTIVE: To study the expression of PTEN and its significance in ampullary adenocarcinoma (AA). DESIGN: We constructed tissue microarrays by using archival tissue from 92 patients (55 males, 37 females; median age, 63 years; age range, 37 to 87 years) with previously untreated AA who underwent pancreaticoduodenectomy at our institution. PTEN expression was evaluated by immunohistochemistry, scored semiquantitatively (based on staining intensity and percentage positive tumor cells), and correlated with clinicopathologic features and survival. RESULTS: Of 92 cases, 23 (25.0%) were PTEN negative. Loss of PTEN expression correlated with lymph node metastasis (P = .004), advanced American Joint Committee on Cancer (AJCC) stage (P = .02), and higher frequency of recurrence (P = .03). Patients with PTEN-negative tumors had shorter disease-free survival (DFS, mean: 89.0 ± 20.8 months) and overall survival (OS, mean: 93.1 ± 19.1 months) than those with PTEN-positive tumors (DFS, mean: 161.4 ± 11.7 months, P = .01; OS, mean: 175.4 ± 11.0 months, P = .001). In multivariate analyses, PTEN expression was a prognostic factor for both DFS and OS, independent of AJCC stage, lymph node status, pathologic tumor (pT) stage, and differentiation. CONCLUSIONS: Loss of PTEN expression is associated with poor DFS and OS in patients with AA after curative surgery. PTEN expression may be used as a prognostic marker for patients with resected AA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact lymph node excision t1 t2 gallbladder cancer population based propensity score matched seer analysis purpose aim study assess effect lymphadenectomy survival t1 t2 gallbladder cancer gbc methods retrospective cohort study patients undergoing surgery t1 t2 gbc 2004 2014 identified surveillance epidemiology end results database effect lymph node excision lne survival assessed using cox regression propensity score methods results total 2112 patients identified 11 4 t1a 18 5 t1b 70 1 t2 tumors mean follow 31 3 months 48 8 patients lne performed mean 3 6 4 3 nodes retrieved cancer specific 5 year survival t1 t2 stages combined 49 6 95 confidence interval ci 45 9 53 6 without lne compared 56 2 95 ci 52 4 60 4 lne performed hazard ratio hr 0 75 95 ci 0 64 0 86 p 0 001 propensity score analyses stages combined confirmed survival benefit hr 0 67 95 ci 0 55 0 80 lne group p 0 001 stratified tumor stages lne significant effect cancer specific survival t1a hr 1 80 95 ci 0 76 4 26 p 0 185 t1b tumors hr 0 95 95 ci 0 57 1 58 p 0 844 whereas persistently revealed advantage patients t2 tumors hr 0 68 95 ci 0 55 0 83 p 0 001 correlation number retrieved lymph nodes n rate found p 0 134 conclusions lne associated improved survival t2 gbc significant survival benefit observed t1a t1b tumors retrieval even lymph nodes reliably predicts nodal status might assist patient selection re resection t1 gbc stn","probabilities":0.9799733,"Title":"Prognostic Impact Of Lymph Node Excision In T1 And T2 Gallbladder Cancer: A Population-Based And Propensity Score-Matched Seer Analysis","Abstract":"Purpose: The aim of this study was to assess the effect of lymphadenectomy on survival in T1/T2 gallbladder cancer (GBC). \n\n Methods: In this retrospective cohort study, patients undergoing surgery for T1/T2 GBC from 2004 to 2014 were identified in the Surveillance, Epidemiology, and End Results database. The effect of lymph node excision (LNE) on survival was assessed using Cox regression and propensity score methods. \n\n Results: A total of 2112 patients were identified: 11.4% had T1a, 18.5% T1b, and 70.1% had T2 tumors. Mean follow-up was 31.3 months. In 48.8% of patients, LNE was performed with a mean of 3.6 ± 4.3 nodes retrieved. Cancer-specific 5-year survival for T1 and T2 stages combined was 49.6% (95% confidence interval (CI), 45.9-53.6%) without LNE compared to 56.2% (95% CI, 52.4-60.4%) if LNE was performed (hazard ratio (HR), 0.75; 95%CI, 0.64-0.86, P < 0.001). Propensity score analyses for both stages combined confirmed this survival benefit with an HR of 0.67 (95% CI, 0.55-0.80) for the LNE group (P < 0.001). Stratified for tumor stages, LNE had no significant effect on cancer-specific survival in T1a (HR, 1.80 (95% CI, 0.76-4.26), P = 0.185) or T1b tumors (HR, 0.95 (95% CI, 0.57-1.58), P = 0.844), whereas it persistently revealed an advantage for patients with T2 tumors (HR 0.68 (95% CI, 0.55-0.83, P < 0.001). No correlation between the number of retrieved lymph nodes and the N+ rate was found (P = 0.134). \n\n Conclusions: LNE is associated with improved survival in T2 GBC. No significant survival benefit was observed in T1a and T1b tumors. The retrieval of even a few lymph nodes reliably predicts the nodal status, which might assist in patient selection for re-resection in T1 GBC.","Source":"STN","category":"HUMAN","training_data":"Prognostic Impact Of Lymph Node Excision In T1 And T2 Gallbladder Cancer: A Population-Based And Propensity Score-Matched Seer Analysis Purpose: The aim of this study was to assess the effect of lymphadenectomy on survival in T1/T2 gallbladder cancer (GBC). \n\n Methods: In this retrospective cohort study, patients undergoing surgery for T1/T2 GBC from 2004 to 2014 were identified in the Surveillance, Epidemiology, and End Results database. The effect of lymph node excision (LNE) on survival was assessed using Cox regression and propensity score methods. \n\n Results: A total of 2112 patients were identified: 11.4% had T1a, 18.5% T1b, and 70.1% had T2 tumors. Mean follow-up was 31.3 months. In 48.8% of patients, LNE was performed with a mean of 3.6 ± 4.3 nodes retrieved. Cancer-specific 5-year survival for T1 and T2 stages combined was 49.6% (95% confidence interval (CI), 45.9-53.6%) without LNE compared to 56.2% (95% CI, 52.4-60.4%) if LNE was performed (hazard ratio (HR), 0.75; 95%CI, 0.64-0.86, P < 0.001). Propensity score analyses for both stages combined confirmed this survival benefit with an HR of 0.67 (95% CI, 0.55-0.80) for the LNE group (P < 0.001). Stratified for tumor stages, LNE had no significant effect on cancer-specific survival in T1a (HR, 1.80 (95% CI, 0.76-4.26), P = 0.185) or T1b tumors (HR, 0.95 (95% CI, 0.57-1.58), P = 0.844), whereas it persistently revealed an advantage for patients with T2 tumors (HR 0.68 (95% CI, 0.55-0.83, P < 0.001). No correlation between the number of retrieved lymph nodes and the N+ rate was found (P = 0.134). \n\n Conclusions: LNE is associated with improved survival in T2 GBC. No significant survival benefit was observed in T1a and T1b tumors. The retrieval of even a few lymph nodes reliably predicts the nodal status, which might assist in patient selection for re-resection in T1 GBC. STN","prediction_labels":"HUMAN"},{"cleaned":"epigenetic downregulation desmin gall bladder cancer reveals potential role disease progression background objectives gall bladder cancer gbc fatal neoplasm globally variable incidence rates improve survival rate patients newer set biomarkers needs discovered early detection better prognosis earlier studies gbc proteomics whole genome methylome data revealed expression desmin significantly downregulated correlated promoter hypermethylation gall bladder carcinogenesis thus evaluate desmin potential biomarker gbc carried detailed follow study methods methylation specific polymerase chain reaction ms pcr n 17 gbc n 23 non tumour control real time quantitative reverse transcription polymerase chain reaction qrt pcr n 14 gbc n 14 adjacent non tumour ant immunohistochemistry n 27 gbc n 14 non tumour immunoblotting n 13 gbc n 13 ant performed surgically removed gall bladder tissue samples results ms pcr analysis showed methylation desmin 88 23 per cent 15 17 gall bladder tumour samples compared non tumour tissues 39 13 9 23 real time qrt pcr analysis revealed significant downregulation desmin expression gbc compared ant tissue confirmed western blot showing reduced expression desmin protein gbc compared non tumour tissue immunohistochemical analysis also showed decreased level desmin e 95 per cent 26 27 tumour cells compared non tumours 35 71 5 14 interpretation conclusions increased frequency desmin promoter methylation responsible significant downregulation indicates potential candidate biomarker gbc requires validation large group patients evaluate clinical utility stn","probabilities":0.7777778,"Title":"Epigenetic Downregulation Of Desmin In Gall Bladder Cancer Reveals Its Potential Role In Disease Progression","Abstract":"Background & objectives: Gall bladder cancer (GBC) is a fatal neoplasm, with a globally variable incidence rates. To improve the survival rate of patients, a newer set of biomarkers needs to be discovered for its early detection and better prognosis. Our earlier studies on GBC proteomics and whole-genome methylome data revealed expression of desmin to be significantly downregulated with correlated promoter hypermethylation during gall bladder carcinogenesis. Thus, to evaluate desmin as a potential biomarker for GBC, we carried out a detailed follow up study. \r\n\r\n Methods: Methylation-specific polymerase chain reaction (MS-PCR) (n=17, GBC and n=23, non-tumour control), real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) [n=14, GBC and n=14, adjacent non-tumour (ANT)], immunohistochemistry (n=27, GBC and n=14, non-tumour) and immunoblotting (n=13, GBC and n=13, ANT) were performed in surgically removed gall bladder tissue samples. \r\n\r\n Results: MS-PCR analysis showed methylation of desmin in 88.23 per cent (15/17) gall bladder tumour samples as compared to non-tumour tissues (39.13%, 9/23). Real-time qRT-PCR analysis revealed a significant downregulation of desmin expression in GBC as compared to ANT tissue. This was further confirmed by western blot, showing reduced expression of desmin protein in GBC, as compared to non-tumour tissue. Immunohistochemical analysis also showed a decreased level of desmin i.e., more than 95 per cent (26/27) in tumour cells compared to non-tumours (35.71%, 5/14). \r\n\r\n Interpretation & conclusions: The increased frequency of desmin promoter methylation which could be responsible for its significant downregulation, indicates its potential as a candidate biomarker for GBC. This requires further validation in a large group of patients to evaluate its clinical utility.","Source":"STN","category":"ANIMAL","training_data":"Epigenetic Downregulation Of Desmin In Gall Bladder Cancer Reveals Its Potential Role In Disease Progression Background & objectives: Gall bladder cancer (GBC) is a fatal neoplasm, with a globally variable incidence rates. To improve the survival rate of patients, a newer set of biomarkers needs to be discovered for its early detection and better prognosis. Our earlier studies on GBC proteomics and whole-genome methylome data revealed expression of desmin to be significantly downregulated with correlated promoter hypermethylation during gall bladder carcinogenesis. Thus, to evaluate desmin as a potential biomarker for GBC, we carried out a detailed follow up study. \r\n\r\n Methods: Methylation-specific polymerase chain reaction (MS-PCR) (n=17, GBC and n=23, non-tumour control), real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) [n=14, GBC and n=14, adjacent non-tumour (ANT)], immunohistochemistry (n=27, GBC and n=14, non-tumour) and immunoblotting (n=13, GBC and n=13, ANT) were performed in surgically removed gall bladder tissue samples. \r\n\r\n Results: MS-PCR analysis showed methylation of desmin in 88.23 per cent (15/17) gall bladder tumour samples as compared to non-tumour tissues (39.13%, 9/23). Real-time qRT-PCR analysis revealed a significant downregulation of desmin expression in GBC as compared to ANT tissue. This was further confirmed by western blot, showing reduced expression of desmin protein in GBC, as compared to non-tumour tissue. Immunohistochemical analysis also showed a decreased level of desmin i.e., more than 95 per cent (26/27) in tumour cells compared to non-tumours (35.71%, 5/14). \r\n\r\n Interpretation & conclusions: The increased frequency of desmin promoter methylation which could be responsible for its significant downregulation, indicates its potential as a candidate biomarker for GBC. This requires further validation in a large group of patients to evaluate its clinical utility. STN","prediction_labels":"ANIMAL"},{"cleaned":"hepatopancreatoduodenectomy cholangiocarcinoma single center review 85 consecutive patients objective outline experience hepatopancreatoduodenectomy hpd treatment cholangiocarcinoma appraise clinical significance challenging procedure background cholangiocarcinomas often exhibit extensive ductal spread invading hepatic hilus lower bile duct tumors completely resected hpd early experiences hpd associated high mortality morbidity leading underestimation survival benefit hpd methods retrospectively reviewed medical records 85 patients cholangiocarcinoma underwent hpd 1992 2011 major hepatectomy performed 79 patients 92 9 combined vascular resection performed 26 patients 30 6 results operating time 762 141 minutes blood loss 2696 1970 ml liver failure common abdominal complication n 64 followed pancreatic fistula n 60 wound sepsis n 33 intra abdominal abscess n 22 refractory ascites n 17 bacteremia n 16 bile leakage n 13 delayed gastric emptying n 12 re laparotomy necessary 9 cases 11 1 overall 19 patients 22 4 exhibited clavien grade 0 ii complications 58 68 2 exhibited grade iii 6 7 1 exhibited grade iv 2 2 4 exhibited grade v mortality overall survival rate 85 patients 79 7 1 year 48 5 3 years 37 4 5 years 32 1 10 years 9 10 5 patients survived 5 years rate survival 53 patients pm0 disease underwent r0 resection favorable 5 10 year survival rates 54 3 46 6 respectively conclusions hpd technically demanding associated high morbidity however surgery performed low mortality offers better probability long term survival selected patients hepatobiliary surgeons consider hpd standard procedure laterally advanced cholangiocarcinomas otherwise unresectable pubmed","probabilities":0.9799733,"Title":"Hepatopancreatoduodenectomy for cholangiocarcinoma: a single-center review of 85 consecutive patients","Abstract":"OBJECTIVE: To outline our experience with hepatopancreatoduodenectomy (HPD) as a treatment for cholangiocarcinoma and to appraise the clinical significance of this challenging procedure. BACKGROUND: Cholangiocarcinomas often exhibit an extensive ductal spread invading from the hepatic hilus to the lower bile duct, and such tumors can be completely resected only by HPD. Early experiences with HPD were associated with high mortality and morbidity, leading to an underestimation of the survival benefit of HPD. METHODS: We retrospectively reviewed the medical records of 85 patients with cholangiocarcinoma who underwent HPD from 1992 to 2011. Major hepatectomy was performed in 79 patients (92.9%), and combined vascular resection was performed in 26 patients (30.6%). RESULTS: The operating time was 762 ± 141 minutes, and blood loss was 2696 ± 1970 mL. Liver failure was the most common abdominal complication (n = 64), followed by pancreatic fistula (n = 60), wound sepsis (n = 33), intra-abdominal abscess (n = 22), refractory ascites (n = 17), bacteremia (n = 16), bile leakage (n = 13), and delayed gastric emptying (n = 12). Re-laparotomy was necessary in 9 cases (11.1%). Overall, 19 patients (22.4%) exhibited Clavien grade 0 to II complications, 58 (68.2%) exhibited grade III, 6 (7.1%) exhibited grade IV, and 2 (2.4%) exhibited grade V (mortality). The overall survival rate for the 85 patients was 79.7% after 1 year, 48.5% after 3 years, 37.4% after 5 years, and 32.1% after 10 years; 9 (10.5%) patients survived for more than 5 years. The rate of survival for the 53 patients with pM0 disease who underwent R0 resection was the most favorable, with 5- and 10-year survival rates of 54.3% and 46.6%, respectively. CONCLUSIONS: HPD is technically demanding and is associated with high morbidity. However, this surgery can be performed with low mortality and offers a better probability of long-term survival in selected patients. As hepatobiliary surgeons, we should consider HPD to be a standard procedure for laterally advanced cholangiocarcinomas that are otherwise unresectable.","Source":"PubMed","category":"HUMAN","training_data":"Hepatopancreatoduodenectomy for cholangiocarcinoma: a single-center review of 85 consecutive patients OBJECTIVE: To outline our experience with hepatopancreatoduodenectomy (HPD) as a treatment for cholangiocarcinoma and to appraise the clinical significance of this challenging procedure. BACKGROUND: Cholangiocarcinomas often exhibit an extensive ductal spread invading from the hepatic hilus to the lower bile duct, and such tumors can be completely resected only by HPD. Early experiences with HPD were associated with high mortality and morbidity, leading to an underestimation of the survival benefit of HPD. METHODS: We retrospectively reviewed the medical records of 85 patients with cholangiocarcinoma who underwent HPD from 1992 to 2011. Major hepatectomy was performed in 79 patients (92.9%), and combined vascular resection was performed in 26 patients (30.6%). RESULTS: The operating time was 762 ± 141 minutes, and blood loss was 2696 ± 1970 mL. Liver failure was the most common abdominal complication (n = 64), followed by pancreatic fistula (n = 60), wound sepsis (n = 33), intra-abdominal abscess (n = 22), refractory ascites (n = 17), bacteremia (n = 16), bile leakage (n = 13), and delayed gastric emptying (n = 12). Re-laparotomy was necessary in 9 cases (11.1%). Overall, 19 patients (22.4%) exhibited Clavien grade 0 to II complications, 58 (68.2%) exhibited grade III, 6 (7.1%) exhibited grade IV, and 2 (2.4%) exhibited grade V (mortality). The overall survival rate for the 85 patients was 79.7% after 1 year, 48.5% after 3 years, 37.4% after 5 years, and 32.1% after 10 years; 9 (10.5%) patients survived for more than 5 years. The rate of survival for the 53 patients with pM0 disease who underwent R0 resection was the most favorable, with 5- and 10-year survival rates of 54.3% and 46.6%, respectively. CONCLUSIONS: HPD is technically demanding and is associated with high morbidity. However, this surgery can be performed with low mortality and offers a better probability of long-term survival in selected patients. As hepatobiliary surgeons, we should consider HPD to be a standard procedure for laterally advanced cholangiocarcinomas that are otherwise unresectable. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance combined preoperative fibrinogen ca199 gallbladder cancer patients aim investigate prognostic value combination preoperative plasma fibrinogen ca199 patients gallbladder carcinoma gbc methods clinicopathological data 154 gbc patients retrospectively reviewed surgery receiver operating characteristic roc curve plotted verify optimum cut values plasma fibrinogen ca199 univariate multivariate survival analyses performed identify factors associated gbc prognosis based hrs calculated via multivariate survival analyses patients elevated plasma fibrinogen ca199 levels allocated score 2 1 elevated plasma fibrinogen level allocated score 1 elevated ca199 level allocated score 1 1 neither abnormalities allocated score 0 results roc curve analysis showed optimum cut values preoperative plasma fibrinogen ca199 3 47 g l 25 45 u ml respectively multivariate analysis indicated elevated preoperative plasma fibrinogen ca199 levels significantly correlated worse overall survival os hr 1 711 95 ci 1 114 2 627 p 0 014 hr 1 842 95 ci 1 111 3 056 p 0 018 combined two parameters area roc curve increased 0 735 preoperative plasma fibrinogen 0 729 preoperative ca199 0 765 combined variable added multivariate analysis combination plasma fibrinogen ca199 p 0 001 resection margin p 0 001 tnm stage p 0 010 independent prognostic factors gbc conclusion combination plasma fibrinogen ca199 may serve efficient independent prognostic biomarker postoperative gbc patients either parameter alone pubmed","probabilities":0.9799733,"Title":"Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients","Abstract":"AIM: To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma (GBC). METHODS: The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. Based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0. RESULTS: ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival (OS) (HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735 (for preoperative plasma fibrinogen only) and 0.729 (for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199 (P < 0.001), resection margin (P < 0.001) and TNM stage (P = 0.010) were independent prognostic factors for GBC. CONCLUSION: The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of combined preoperative fibrinogen and CA199 in gallbladder cancer patients AIM: To investigate the prognostic value of the combination of preoperative plasma fibrinogen and CA199 in patients with gallbladder carcinoma (GBC). METHODS: The clinicopathological data of 154 GBC patients were retrospectively reviewed after surgery. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cut-off values for plasma fibrinogen and CA199. Univariate and multivariate survival analyses were performed to identify the factors associated with GBC prognosis. Based on the HRs calculated via multivariate survival analyses, patients with elevated plasma fibrinogen and CA199 levels were allocated a score of 2.1; those with an elevated plasma fibrinogen level only were allocated a score of 1, those with an elevated CA199 level only were allocated a score of 1.1, and those with neither of these abnormalities were allocated a score of 0. RESULTS: ROC curve analysis showed that the optimum cut-off values for preoperative plasma fibrinogen and CA199 were 3.47 g/L and 25.45 U/mL, respectively. Multivariate analysis indicated that elevated preoperative plasma fibrinogen and CA199 levels were significantly correlated with worse overall survival (OS) (HR = 1.711, 95%CI: 1.114-2.627, P = 0.014, and HR = 1.842, 95%CI: 1.111-3.056, P = 0.018). When we combined these two parameters, the area under the ROC curve increased from 0.735 (for preoperative plasma fibrinogen only) and 0.729 (for preoperative CA199 only) to 0.765. When this combined variable was added to the multivariate analysis, the combination of plasma fibrinogen and CA199 (P < 0.001), resection margin (P < 0.001) and TNM stage (P = 0.010) were independent prognostic factors for GBC. CONCLUSION: The combination of plasma fibrinogen and CA199 may serve as a more efficient independent prognostic biomarker for postoperative GBC patients than either parameter alone. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role systematic hepatic pedicle lymphadenectomy intrahepatic cholangiocarcinoma review 17 years experience tertiary institution background although use lymphadenectomy treatment extrahepatic cholangiocarcinoma established routine lymphadenectomy intrahepatic cholangiocarcinoma icc remains controversial examined factors predicting survival patients icc resection compared outcomes patients without systematic hepatic pedicle lymph node dissection lnd methods data retrospectively collected 215 patients icc underwent liver resection years 1995 2012 patients divided n 102 47 4 received lnd ln d n 113 52 6 ln d0 results demographic data similar 2 groups except presence preoperative symptom p 019 liver cirrhosis p 001 carbohydrate antigen 19 9 p 003 tumor location according hepatic lobe p 001 type hepatectomy p 001 adjuvant treatment p 001 postoperative complications p 028 tumor recurrence distant site observed 102 patients 68 5 ln metastasis independently associated risk distant recurrence p 002 ln d ln d0 groups differ overall survival p 101 disease free survival p 111 poorly differentiated histologic grade p 016 ln metastasis p 001 identified independent predictor overall survival conclusion routine lnd icc show survival benefits however ln sampling might useful nodal staging essential factor predicting outcome deciding whether apply adjuvant treatment pubmed","probabilities":0.9799733,"Title":"Is there a role for systematic hepatic pedicle lymphadenectomy in intrahepatic cholangiocarcinoma? A review of 17 years of experience in a tertiary institution","Abstract":"BACKGROUND: Although use of lymphadenectomy for treatment of extrahepatic cholangiocarcinoma is established, routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) remains controversial. We examined the factors predicting survival in patients after ICC resection and compared outcomes of patients with and without systematic hepatic pedicle lymph node dissection (LND). METHODS: Data were retrospectively collected for 215 patients with ICC who underwent liver resection during the years 1995-2012. Patients were divided into those (n = 102; 47.4%) who received LND (LN [D]) and those (n = 113; 52.6%) who did not (LN [D0]). RESULTS: Demographic data were similar between the 2 groups except for presence of preoperative symptom (P = .019) and liver cirrhosis (P < .001), carbohydrate antigen 19-9 (P = .003), tumor location according to the hepatic lobe (P < .001), type of hepatectomy (P < .001), adjuvant treatment (P < .001), and postoperative complications (P = .028). Tumor recurrence at a distant site was observed in 102 patients (68.5%). LN metastasis was independently associated with risk of distant recurrence (P = .002). The LN (D) and LN (D0) groups did not differ in overall survival (P = .101) or disease-free survival (P = .111). Poorly differentiated histologic grade (P = .016) and LN metastasis (P < .001) was identified as an independent predictor of overall survival. CONCLUSION: Routine LND for ICC did not show survival benefits; however, LN sampling might be useful for nodal staging, an essential factor in predicting outcome and deciding whether to apply adjuvant treatment.","Source":"PubMed","category":"HUMAN","training_data":"Is there a role for systematic hepatic pedicle lymphadenectomy in intrahepatic cholangiocarcinoma? A review of 17 years of experience in a tertiary institution BACKGROUND: Although use of lymphadenectomy for treatment of extrahepatic cholangiocarcinoma is established, routine lymphadenectomy for intrahepatic cholangiocarcinoma (ICC) remains controversial. We examined the factors predicting survival in patients after ICC resection and compared outcomes of patients with and without systematic hepatic pedicle lymph node dissection (LND). METHODS: Data were retrospectively collected for 215 patients with ICC who underwent liver resection during the years 1995-2012. Patients were divided into those (n = 102; 47.4%) who received LND (LN [D]) and those (n = 113; 52.6%) who did not (LN [D0]). RESULTS: Demographic data were similar between the 2 groups except for presence of preoperative symptom (P = .019) and liver cirrhosis (P < .001), carbohydrate antigen 19-9 (P = .003), tumor location according to the hepatic lobe (P < .001), type of hepatectomy (P < .001), adjuvant treatment (P < .001), and postoperative complications (P = .028). Tumor recurrence at a distant site was observed in 102 patients (68.5%). LN metastasis was independently associated with risk of distant recurrence (P = .002). The LN (D) and LN (D0) groups did not differ in overall survival (P = .101) or disease-free survival (P = .111). Poorly differentiated histologic grade (P = .016) and LN metastasis (P < .001) was identified as an independent predictor of overall survival. CONCLUSION: Routine LND for ICC did not show survival benefits; however, LN sampling might be useful for nodal staging, an essential factor in predicting outcome and deciding whether to apply adjuvant treatment. PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcomes surgery 2010 classification based intraductal papillary neoplasm bile duct case control study single japanese institution experience special attention mucin expression patterns introduction world health organization proposed integrated classification intraductal papillary neoplasm bile duct ipnb 2010 however ipnb reportedly shows considerable geographic variation japanese single institution study examined outcomes surgery ipnb prognostic impact immunohistochemical mucin expression patterns materials methods patients ipnb identified 413 patients underwent curative intent surgery biliary tract excluding gallbladder neoplasms 1992 2016 retrospective macro microscopic reevaluation resected specimens clinicopathological variables analyzed results twenty two 5 2010 classification based patients ipnb identified 391 patients common type cholangiocarcinoma histopathological grade low intermediate 2 patients 9 high 8 36 invasive carcinoma ica 12 55 10 year overall survival rate 100 10 patients low high grade ipnb 69 12 patients ica rates significantly p 0 018 marginally p 0 089 better 38 391 cholangiocarcinoma patients 12 patients ica r0 r1 resection muc5ac muc6 expression significantly affected survival notably seven patients ica exhibiting muc5ac expression survived throughout study period four five patients ica exhibit muc5ac expression died recurrence vs without muc5ac 10 year overall survival 100 vs 60 respectively p 0 018 conclusion 24 year single institution experience suggests japanese patients ipnb favorably respond surgery even ica muc5ac muc6 expression may predictive favorable outcomes pubmed","probabilities":0.9799733,"Title":"Outcomes of surgery for 2010 WHO classification-based intraductal papillary neoplasm of the bile duct: Case-control study of a single Japanese institution's experience with special attention to mucin expression patterns","Abstract":"INTRODUCTION: The World Health Organization (WHO) proposed an integrated classification for intraductal papillary neoplasm of the bile duct (IPNB) in 2010. However, IPNB reportedly shows considerable geographic variation. This Japanese single-institution study examined outcomes of surgery for IPNB and the prognostic impact of immunohistochemical mucin expression patterns. MATERIALS AND METHODS: Patients with IPNB were identified from 413 patients who underwent curative-intent surgery for biliary tract (excluding gallbladder) neoplasms from 1992 to 2016 by retrospective macro- and microscopic reevaluation of resected specimens. Their clinicopathological variables were analyzed. RESULTS: Twenty-two (5%) 2010 WHO classification-based patients with IPNB were identified. The other 391 patients had common-type cholangiocarcinoma. The histopathological grade was low/intermediate in 2 patients (9%), high in 8 (36%), and invasive carcinoma (ICa) in 12 (55%). The 10-year overall survival rate was 100% in 10 patients with low-high grade IPNB and 69% in 12 patients with ICa. These rates were significantly (p = 0.018) or marginally (p = 0.089) better than that (38%) of 391 other-cholangiocarcinoma patients. In the 12 patients with ICa, R0 or R1 resection, MUC5AC, and MUC6 expression significantly affected survival. Notably, all seven patients with ICa exhibiting MUC5AC expression survived throughout the study period, while four of five patients with ICa who did not exhibit MUC5AC expression died of recurrence (with vs. without MUC5AC: 10-year overall survival, 100% vs. 60%, respectively; p = 0.018). CONCLUSION: Our 24-year, single institution's experience suggests that Japanese patients with IPNB favorably respond to surgery, even with ICa. MUC5AC and MUC6 expression may be predictive of favorable outcomes.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes of surgery for 2010 WHO classification-based intraductal papillary neoplasm of the bile duct: Case-control study of a single Japanese institution's experience with special attention to mucin expression patterns INTRODUCTION: The World Health Organization (WHO) proposed an integrated classification for intraductal papillary neoplasm of the bile duct (IPNB) in 2010. However, IPNB reportedly shows considerable geographic variation. This Japanese single-institution study examined outcomes of surgery for IPNB and the prognostic impact of immunohistochemical mucin expression patterns. MATERIALS AND METHODS: Patients with IPNB were identified from 413 patients who underwent curative-intent surgery for biliary tract (excluding gallbladder) neoplasms from 1992 to 2016 by retrospective macro- and microscopic reevaluation of resected specimens. Their clinicopathological variables were analyzed. RESULTS: Twenty-two (5%) 2010 WHO classification-based patients with IPNB were identified. The other 391 patients had common-type cholangiocarcinoma. The histopathological grade was low/intermediate in 2 patients (9%), high in 8 (36%), and invasive carcinoma (ICa) in 12 (55%). The 10-year overall survival rate was 100% in 10 patients with low-high grade IPNB and 69% in 12 patients with ICa. These rates were significantly (p = 0.018) or marginally (p = 0.089) better than that (38%) of 391 other-cholangiocarcinoma patients. In the 12 patients with ICa, R0 or R1 resection, MUC5AC, and MUC6 expression significantly affected survival. Notably, all seven patients with ICa exhibiting MUC5AC expression survived throughout the study period, while four of five patients with ICa who did not exhibit MUC5AC expression died of recurrence (with vs. without MUC5AC: 10-year overall survival, 100% vs. 60%, respectively; p = 0.018). CONCLUSION: Our 24-year, single institution's experience suggests that Japanese patients with IPNB favorably respond to surgery, even with ICa. MUC5AC and MUC6 expression may be predictive of favorable outcomes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"perineural invasion prognostic factor intrahepatic cholangiocarcinoma curative resection potential indication postoperative chemotherapy retrospective cohort study background past four decades incidence cholangiocarcinoma especially intrahepatic cholangiocarcinoma icc raised rapidly worldwide completeness resection max size tumor etc widely recognized prognostic factors however prognosis significance perineural invasion pni recurrence free survival rfs overall survival os icc patients controversial methods icc patients underwent curative hepatectomy diagnosed pathologically retrospectively analyzed patients grouped existence pni outcomes compared groups potential relationship pni postoperative chemotherapy also investigated results significant difference demographic clinical staging tumor index two groups except positive hepatitis b surface antigen ca19 9 pni negative group showed better prognosis rfs p 0 0001 os p 0 0001 cox regression analyses showed pni independent risk factor rfs os icc postoperative chemotherapy showed better effects whole cohort rfs p 0 0023 os p 0 0011 pni negative group postoperative chemotherapy also showed significant benefits rfs os however pni positive group p 0 4920 rfs p 0 8004 os conclusion pni independent risk factor r0 resected icc presenting worse recurrence survival outcomes meanwhile negative pni may act indication postoperative chemotherapy google scholar","probabilities":0.9799733,"Title":"Perineural Invasion As A Prognostic Factor For Intrahepatic Cholangiocarcinoma After Curative Resection And A Potential Indication For Postoperative Chemotherapy: A Retrospective Cohort Study","Abstract":"Background\nIn the past four decades, the incidence of cholangiocarcinoma, especially intrahepatic cholangiocarcinoma (ICC), has raised rapidly worldwide. Completeness of resection, max size of tumor and etc. are widely recognized as prognostic factors. However, the prognosis significance of perineural invasion (PNI) on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is controversial.\nMethods\nICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Patients were grouped by existence of PNI and outcomes were compared between groups. The potential relationship between PNI and postoperative chemotherapy was also investigated.\nResults\nThere was no significant difference in demographic, clinical staging or tumor index between two groups, except positive hepatitis B surface antigen and CA19–9. PNI negative group showed a better prognosis in RFS (P < 0.0001) and OS (P < 0.0001). COX regression analyses showed PNI as an independent risk factor in RFS and OS. ICC with postoperative chemotherapy showed better effects in the whole cohort on both RFS (P = 0.0023) and OS (P = 0.0011). In PNI negative group, postoperative chemotherapy also showed significant benefits on RFS and OS, however not in PNI positive group (P = 0.4920 in RFS and P = 0.8004 in OS).\nConclusion\nPNI was an independent risk factor in R0-resected ICC, presenting worse recurrence and survival outcomes. Meanwhile, negative PNI may act as an indication of postoperative chemotherapy.","Source":"Google Scholar","category":"HUMAN","training_data":"Perineural Invasion As A Prognostic Factor For Intrahepatic Cholangiocarcinoma After Curative Resection And A Potential Indication For Postoperative Chemotherapy: A Retrospective Cohort Study Background\nIn the past four decades, the incidence of cholangiocarcinoma, especially intrahepatic cholangiocarcinoma (ICC), has raised rapidly worldwide. Completeness of resection, max size of tumor and etc. are widely recognized as prognostic factors. However, the prognosis significance of perineural invasion (PNI) on recurrence-free survival (RFS) and overall survival (OS) in ICC patients is controversial.\nMethods\nICC patients who underwent curative hepatectomy and diagnosed pathologically were retrospectively analyzed. Patients were grouped by existence of PNI and outcomes were compared between groups. The potential relationship between PNI and postoperative chemotherapy was also investigated.\nResults\nThere was no significant difference in demographic, clinical staging or tumor index between two groups, except positive hepatitis B surface antigen and CA19–9. PNI negative group showed a better prognosis in RFS (P < 0.0001) and OS (P < 0.0001). COX regression analyses showed PNI as an independent risk factor in RFS and OS. ICC with postoperative chemotherapy showed better effects in the whole cohort on both RFS (P = 0.0023) and OS (P = 0.0011). In PNI negative group, postoperative chemotherapy also showed significant benefits on RFS and OS, however not in PNI positive group (P = 0.4920 in RFS and P = 0.8004 in OS).\nConclusion\nPNI was an independent risk factor in R0-resected ICC, presenting worse recurrence and survival outcomes. Meanwhile, negative PNI may act as an indication of postoperative chemotherapy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clustering patients intrahepatic cholangiocarcinoma based serum periostin may predictive prognosis effective serum biomarker may improve cholangiocarcinoma cca management periostin pn demonstrated associated aggressive cca current study evaluated pn blood serum diagnostic prognostic potential patients cca sera 68 patients cca collected prior treatment pn levels measured using elisa sera 50 normal controls 6 patients benign liver diseases 2 hepatocellular carcinoma 21 breast cancer analyzed immunohistochemistry pn cca tissues also investigated data analyzed using mann whitney u test kaplan meier log rank tests cox proportional hazard regression models fisher exact tests median serum pn level patients cca significantly increased compared healthy controls patients benign liver diseases patients breast cancer p 0 05 using optimal threshold value 94 ng ml pn diagnostic values cca compared conditions demonstrated sensitivity level 0 38 95 confidence interval ci 0 27 0 51 specificity 0 90 95 ci 0 81 0 96 accuracy 0 66 95 ci 0 58 0 74 positive predictive value 0 76 95 ci 0 59 0 89 negative predictive value 0 63 95 ci 0 53 0 72 p 0 001 furthermore pn stain stromal fibroblasts cca tissues associated serum pn levels p 0 001 patients cca classified low 94 ng ml high pn 94 ng ml accordingly high serum tissue pn levels significantly associated reduced survival rate p 0 001 p 0 033 respectively serum pn independent prognostic factor hazard ratio 3 197 p 0 001 conclusion serum pn may used divide patients intrahepatic cca high low pn groups elevated serum pn may utilized marker poor prognosis patients cca stn","probabilities":0.88235295,"Title":"Clustering Of Patients With Intrahepatic Cholangiocarcinoma Based On Serum Periostin May Be Predictive Of Prognosis","Abstract":"An effective serum biomarker may improve cholangiocarcinoma (CCA) management. Periostin (PN) has been demonstrated to be associated with aggressive CCA. The current study evaluated PN in blood serum for its diagnostic and prognostic potential in patients with CCA. Sera of 68 patients with CCA were collected prior to treatment, and PN levels were measured using an ELISA. Sera from 50 normal controls, 6 patients with benign liver diseases, 2 with hepatocellular carcinoma and 21 with breast cancer were analyzed. Immunohistochemistry of PN in CCA tissues was also investigated. The data were analyzed using the Mann-Whitney U test, Kaplan-Meier log rank tests, Cox proportional hazard regression models and Fisher's exact tests. The median serum PN level in patients with CCA was significantly increased compared with that in healthy controls, patients with benign liver diseases and patients with breast cancer (all P<0.05). Using an optimal threshold value of 94 ng/ml PN, the diagnostic values for CCA compared with other conditions demonstrated a sensitivity level of 0.38 [95% confidence interval (CI), 0.27-0.51], specificity of 0.90 (95% CI, 0.81-0.96), accuracy of 0.66 (95% CI, 0.58-0.74), positive predictive value of 0.76 (95% CI, 0.59-0.89) and negative predictive value of 0.63 (95% CI, 0.53-0.72) (P<0.001). Furthermore, PN stain in stromal fibroblasts in CCA tissues was associated with serum PN levels (P=0.001), and patients with CCA were classified as low (≤94 ng/ml) or high PN (>94 ng/ml) accordingly. High serum and tissue PN levels were significantly associated with reduced survival rate (P<0.001 and P=0.033, respectively). Serum PN was an independent prognostic factor with a hazard ratio of 3.197 (P=0.001). In conclusion, serum PN may be used to divide patients with intrahepatic CCA into high and low PN groups. Elevated serum PN may be utilized as a marker of poor prognosis in patients with CCA.","Source":"STN","category":"HUMAN","training_data":"Clustering Of Patients With Intrahepatic Cholangiocarcinoma Based On Serum Periostin May Be Predictive Of Prognosis An effective serum biomarker may improve cholangiocarcinoma (CCA) management. Periostin (PN) has been demonstrated to be associated with aggressive CCA. The current study evaluated PN in blood serum for its diagnostic and prognostic potential in patients with CCA. Sera of 68 patients with CCA were collected prior to treatment, and PN levels were measured using an ELISA. Sera from 50 normal controls, 6 patients with benign liver diseases, 2 with hepatocellular carcinoma and 21 with breast cancer were analyzed. Immunohistochemistry of PN in CCA tissues was also investigated. The data were analyzed using the Mann-Whitney U test, Kaplan-Meier log rank tests, Cox proportional hazard regression models and Fisher's exact tests. The median serum PN level in patients with CCA was significantly increased compared with that in healthy controls, patients with benign liver diseases and patients with breast cancer (all P<0.05). Using an optimal threshold value of 94 ng/ml PN, the diagnostic values for CCA compared with other conditions demonstrated a sensitivity level of 0.38 [95% confidence interval (CI), 0.27-0.51], specificity of 0.90 (95% CI, 0.81-0.96), accuracy of 0.66 (95% CI, 0.58-0.74), positive predictive value of 0.76 (95% CI, 0.59-0.89) and negative predictive value of 0.63 (95% CI, 0.53-0.72) (P<0.001). Furthermore, PN stain in stromal fibroblasts in CCA tissues was associated with serum PN levels (P=0.001), and patients with CCA were classified as low (≤94 ng/ml) or high PN (>94 ng/ml) accordingly. High serum and tissue PN levels were significantly associated with reduced survival rate (P<0.001 and P=0.033, respectively). Serum PN was an independent prognostic factor with a hazard ratio of 3.197 (P=0.001). In conclusion, serum PN may be used to divide patients with intrahepatic CCA into high and low PN groups. Elevated serum PN may be utilized as a marker of poor prognosis in patients with CCA. STN","prediction_labels":"HUMAN"},{"cleaned":"declined preoperative aspartate aminotransferase neutrophil ratio index predicts poor prognosis patients intrahepatic cholangiocarcinoma hepatectomy purpose various inflammation based prognostic biomarkers platelet lymphocyte ratio neutrophil lymphocyte ratio related poor survival patients intrahepatic cholangiocarcinoma icc study aims investigate prognostic value aspartate aminotransferase neutrophil ratio index anri icc hepatic resection materials methods data 184 patients icc hepatectomy retrospectively reviewed cut value anriwas determined receiver operating characteristic curve preoperative anri clinicopathological variables analyzed predictive value preoperative anri prognosis icc identified univariate multivariate analyses results optimal cut value anri 6 7 anri associated tumor size tumor recurrence white blood cell neutrophil count aspartate aminotransferase alanine transaminase univariate analysis showed anri sex tumor number tumor size tumor differentiation lymph node metastasis resection margin clinical tnm stage neutrophil count carcinoembryonic antigen markedly correlated overall survival os disease free survival dfs patients icc multivariable analyses revealed anri tumor size 6 cm poor tumor differentiation r1 resection margin independent prognostic factors os dfs additionally preoperative anri also significant value predict prognosis various subgroups icc including serum hepatitis b surface antigen negative preoperative elevated carbohydrate antigen 19 9 patients conclusion preoperative declined anri noninvasive simple effective predictor poor prognosis patients icc hepatectomy pubmed","probabilities":0.962963,"Title":"Declined Preoperative Aspartate Aminotransferase to Neutrophil Ratio Index Predicts Poor Prognosis in Patients with Intrahepatic Cholangiocarcinoma after Hepatectomy","Abstract":"PURPOSE: Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. MATERIALS AND METHODS: Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRIwas determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. RESULTS: The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. CONCLUSION: Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy.","Source":"PubMed","category":"HUMAN","training_data":"Declined Preoperative Aspartate Aminotransferase to Neutrophil Ratio Index Predicts Poor Prognosis in Patients with Intrahepatic Cholangiocarcinoma after Hepatectomy PURPOSE: Various inflammation-based prognostic biomarkers such as the platelet to lymphocyte ratio and neutrophil to lymphocyte ratio, are related to poor survival in patients with intrahepatic cholangiocarcinoma (ICC). This study aims to investigate the prognostic value of the aspartate aminotransferase to neutrophil ratio index (ANRI) in ICC after hepatic resection. MATERIALS AND METHODS: Data of 184 patients with ICC after hepatectomy were retrospectively reviewed. The cut-off value of ANRIwas determined by a receiver operating characteristic curve. Preoperative ANRI and clinicopathological variables were analyzed. The predictive value of preoperative ANRI for prognosis of ICC was identified by univariate and multivariate analyses. RESULTS: The optimal cut-off value of ANRI was 6.7. ANRI was associated with tumor size, tumor recurrence, white blood cell, neutrophil count, aspartate aminotransferase, and alanine transaminase. Univariate analysis showed that ANRI, sex, tumor number, tumor size, tumor differentiation, lymph node metastasis, resection margin, clinical TNM stage, neutrophil count, and carcinoembryonic antigen were markedly correlated with overall survival (OS) and disease-free survival (DFS) in patients with ICC. Multivariable analyses revealed that ANRI, a tumor size > 6 cm, poor tumor differentiation, and an R1 resection margin were independent prognostic factors for both OS and DFS. Additionally, preoperative ANRI also had a significant value to predict prognosis in various subgroups of ICC, including serum hepatitis B surface antigen‒negative and preoperative elevated carbohydrate antigen 19-9 patients. CONCLUSION: Preoperative declined ANRI is a noninvasive, simple, and effective predictor of poor prognosis in patients with ICC after hepatectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiological dimensions association type 2 diabetes cancer review observational studies type 2 diabetes t2d major cause complications death many countries possible causal relation t2d cancer aim many research investigations view importance topic carried narrative review observational studies summarize available evidence association t2d cancer deal problem abundance published studies reviewed december 2017 literature meta analyses observational studies first reviewed cohort studies reported meta analyses recent publication found association t2d risk colorectal cancer robust whereas evidence associations cancer sites lower observed associations overestimated due publication bias unmeasured confounders obesity surveillance bias conclusion probable causal association t2d risk colorectal cancer confirmed possible causal association pancreatic endometrial hepatocellular gallbladder carcinoma also found substantial uncertainty exists cancer sites pubmed","probabilities":0.9799733,"Title":"Epidemiological dimensions of the association between type 2 diabetes and cancer: A review of observational studies","Abstract":"Type 2 diabetes (T2D) is a major cause of complications and death in many countries. The possible causal relation between T2D and cancer has been the aim of many research investigations. In view of the importance of the topic we carried out a narrative review of observational studies to summarize the available evidence of the association between T2D and cancer. To deal with the problem of abundance of published studies, we reviewed up to December 2017, the literature of meta-analyses of observational studies first, then we reviewed cohort studies not reported in meta-analyses because of more recent publication. We found that the association of T2D with risk of colorectal cancer was robust, whereas the evidence of the associations with other cancer sites was lower. Some of the observed associations could be overestimated, due to publication bias, unmeasured confounders (such as obesity) and surveillance bias. In conclusion a probable causal association of T2D with risk of colorectal cancer was confirmed. A possible causal association with pancreatic, endometrial, hepatocellular and gallbladder carcinoma was also found. Substantial uncertainty exists for other cancer sites.","Source":"PubMed","category":"HUMAN","training_data":"Epidemiological dimensions of the association between type 2 diabetes and cancer: A review of observational studies Type 2 diabetes (T2D) is a major cause of complications and death in many countries. The possible causal relation between T2D and cancer has been the aim of many research investigations. In view of the importance of the topic we carried out a narrative review of observational studies to summarize the available evidence of the association between T2D and cancer. To deal with the problem of abundance of published studies, we reviewed up to December 2017, the literature of meta-analyses of observational studies first, then we reviewed cohort studies not reported in meta-analyses because of more recent publication. We found that the association of T2D with risk of colorectal cancer was robust, whereas the evidence of the associations with other cancer sites was lower. Some of the observed associations could be overestimated, due to publication bias, unmeasured confounders (such as obesity) and surveillance bias. In conclusion a probable causal association of T2D with risk of colorectal cancer was confirmed. A possible causal association with pancreatic, endometrial, hepatocellular and gallbladder carcinoma was also found. Substantial uncertainty exists for other cancer sites. PubMed","prediction_labels":"HUMAN"},{"cleaned":"early versus late recurrence intrahepatic cholangiocarcinoma resection curative intent background objective study investigate characteristics treatment prognosis early versus late recurrence intrahepatic cholangiocarcinoma icc hepatic resection methods patients underwent resection curative intent icc identified multi institutional database data clinicopathological characteristics initial operative details timing sites recurrence recurrence management long term outcomes analysed results total 933 patients included median follow 22 months 685 patients 73 4 per cent experienced recurrence icc 406 59 3 per cent developed intrahepatic disease recurrence optimal cutoff value differentiate early 540 patients 78 8 per cent versus late 145 21 2 per cent recurrence defined 24 months patients early recurrence extrahepatic disease often 44 1 per cent versus 28 3 per cent late recurrence p 0 001 whereas late recurrence often intrahepatic 71 7 per cent versus 55 9 per cent early recurrence p 0 001 time recurrence overall survival worse among patients early versus late recurrence median 10 versus 18 months respectively p 0 029 multivariable analysis tumour characteristics including tumour size number lesions satellite lesions associated increased risk early intrahepatic recurrence contrast presence liver cirrhosis independently associated increased likelihood late intrahepatic recurrence hazard ratio 1 99 95 per cent c 1 11 3 56 p 0 019 conclusion early late recurrence curative resection icc associated different risk factors prognosis data timing recurrence may inform decisions degree postoperative surveillance well help counsel patients regard risk recurrence pubmed","probabilities":0.9799733,"Title":"Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent","Abstract":"BACKGROUND: The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. METHODS: Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. RESULTS: A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). CONCLUSION: Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence.","Source":"PubMed","category":"HUMAN","training_data":"Early versus late recurrence of intrahepatic cholangiocarcinoma after resection with curative intent BACKGROUND: The objective of this study was to investigate the characteristics, treatment and prognosis of early versus late recurrence of intrahepatic cholangiocarcinoma (ICC) after hepatic resection. METHODS: Patients who underwent resection with curative intent for ICC were identified from a multi-institutional database. Data on clinicopathological characteristics, initial operative details, timing and sites of recurrence, recurrence management and long-term outcomes were analysed. RESULTS: A total of 933 patients were included. With a median follow-up of 22 months, 685 patients (73·4 per cent) experienced recurrence of ICC; 406 of these (59·3 per cent) developed only intrahepatic disease recurrence. The optimal cutoff value to differentiate early (540 patients, 78·8 per cent) versus late (145, 21·2 per cent) recurrence was defined as 24 months. Patients with early recurrence had extrahepatic disease more often (44·1 per cent versus 28·3 per cent in those with late recurrence; P < 0·001), whereas late recurrence was more often only intrahepatic (71·7 per cent versus 55·9 per cent for early recurrence; P < 0·001). From time of recurrence, overall survival was worse among patients who had early versus late recurrence (median 10 versus 18 months respectively; P = 0·029). In multivariable analysis, tumour characteristics including tumour size, number of lesions and satellite lesions were associated with an increased risk of early intrahepatic recurrence. In contrast, only the presence of liver cirrhosis was independently associated with an increased likelihood of late intrahepatic recurrence (hazard ratio 1·99, 95 per cent c.i. 1·11 to 3·56; P = 0·019). CONCLUSION: Early and late recurrence after curative resection for ICC are associated with different risk factors and prognosis. Data on the timing of recurrence may inform decisions about the degree of postoperative surveillance, as well as help counsel patients with regard to their risk of recurrence. PubMed","prediction_labels":"HUMAN"},{"cleaned":"adjuvant systemic therapy resection node positive gallbladder cancer time well designed trial results us national retrospective cohort study background ideal oncologic management gallbladder carcinoma gbca complete surgical resection unclear sought define benefit post resection adjuvant systemic chemotherapy alone t2 greater gallbladder carcinoma utilising large national dataset study design national cancer data base ncdb 2004 2012 cohort retrospectively reviewed patients gbca t2 undergoing curative intent resection surviving least 6 weeks univariate group comparisons unadjusted kaplan meier adjusted cox proportional hazards analyzed overall survival results 4373 patients included n 2479 t2 n 1894 t3 4 overall 22 1 patients received adjuvant chemotherapy use multi agent chemotherapy increased study period patients receiving adjuvant therapy younger fewer comorbidities often node positive likely r1 margins receiving surgery alone unadjusted overall survival improved patients node positive disease well inadequate nodal staging benefit chemotherapy persisted adjustment patient tumor factors conclusion adjuvant systemic chemotherapy associated survival benefit patients t2 greater gbca node positive disease recommend multidisciplinary approach patients less 1 4 currently receive adjuvant chemotherapy future clinical trials address adjuvant chemotherapy node positive gbca pubmed","probabilities":0.9799733,"Title":"Adjuvant systemic therapy after resection of node positive gallbladder cancer: Time for a well-designed trial? (Results of a US-national retrospective cohort study)","Abstract":"BACKGROUND: Ideal oncologic management of gallbladder carcinoma (GBCA) after complete surgical resection is unclear. We sought to define benefit of post-resection adjuvant systemic chemotherapy alone in T2 or greater gallbladder carcinoma utilising a large national dataset. STUDY DESIGN: The National Cancer Data Base (NCDB) 2004-2012 cohort was retrospectively reviewed for patients with GBCA (T2+) undergoing curative-intent resection and surviving at least 6 weeks. Univariate group comparisons, unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyzed overall survival. RESULTS: 4373 patients were included (N = 2479 T2, N = 1894 T3/4). Overall, 22.1% of patients received adjuvant chemotherapy. Use of multi-agent chemotherapy increased during the study period. Patients receiving adjuvant therapy were younger, had fewer comorbidities, more often node-positive and more likely R1-margins than those receiving surgery alone. Unadjusted overall survival was improved in all patients with node-positive disease as well as for those with inadequate nodal staging. The benefit of chemotherapy persisted after adjustment for patient and tumor factors. CONCLUSION: Adjuvant systemic chemotherapy is associated with survival benefit in patients with T2 or greater GBCA with node positive disease. We recommend a multidisciplinary approach in these patients as less than 1-in-4 of them currently receive adjuvant chemotherapy. Future clinical trials should address adjuvant chemotherapy in node positive GBCA.","Source":"PubMed","category":"HUMAN","training_data":"Adjuvant systemic therapy after resection of node positive gallbladder cancer: Time for a well-designed trial? (Results of a US-national retrospective cohort study) BACKGROUND: Ideal oncologic management of gallbladder carcinoma (GBCA) after complete surgical resection is unclear. We sought to define benefit of post-resection adjuvant systemic chemotherapy alone in T2 or greater gallbladder carcinoma utilising a large national dataset. STUDY DESIGN: The National Cancer Data Base (NCDB) 2004-2012 cohort was retrospectively reviewed for patients with GBCA (T2+) undergoing curative-intent resection and surviving at least 6 weeks. Univariate group comparisons, unadjusted Kaplan-Meier and adjusted Cox proportional hazards analyzed overall survival. RESULTS: 4373 patients were included (N = 2479 T2, N = 1894 T3/4). Overall, 22.1% of patients received adjuvant chemotherapy. Use of multi-agent chemotherapy increased during the study period. Patients receiving adjuvant therapy were younger, had fewer comorbidities, more often node-positive and more likely R1-margins than those receiving surgery alone. Unadjusted overall survival was improved in all patients with node-positive disease as well as for those with inadequate nodal staging. The benefit of chemotherapy persisted after adjustment for patient and tumor factors. CONCLUSION: Adjuvant systemic chemotherapy is associated with survival benefit in patients with T2 or greater GBCA with node positive disease. We recommend a multidisciplinary approach in these patients as less than 1-in-4 of them currently receive adjuvant chemotherapy. Future clinical trials should address adjuvant chemotherapy in node positive GBCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"body mass index weight change initial period chemotherapy affect survival outcome advanced biliary tract cancer patients background impact obesity survival known vary different cancers advanced biliary tract cancer rarely analyzed relationship obesity prognosis performed study evaluate bmi body weight change prognostic factors advanced biliary tract cancer patients palliative chemotherapy methods january 2005 december 2016 two hundred seventy six patients underwent chemotherapy biliary tract cancer retrospectively analyzed relationship bmi kg m2 clinical outcomes including overall progression free survival assessed additionally relationship change body composition overall survival evaluated results median overall survival 9 7 months underweight patients 10 1 months normal patients 15 8 months overweight group 13 1 months obese patients respectively p 0 047 univariate analysis showed bmi stage iii age less 64 year old gallbladder cancer operation radiotherapy ecog performance significantly associated better survival compared normal patients overweight patients bmi 23 24 9kg m2 reduced risk mortality multivariate analysis hr 0 632 95 ci 0 436 0 918 p 0 016 additional analysis effect changes body weight bmi overall survival decrease body weight bmi hr 1 410 95 ci 1 168 1 986 p 0 046 associated shorter overall survival conclusion overweight status maintenance body weight initial period chemotherapy important independent predictors better overall survival advanced biliary tract cancer patients pubmed","probabilities":0.9799733,"Title":"Body mass index and weight change during initial period of chemotherapy affect survival outcome in advanced biliary tract cancer patients","Abstract":"BACKGROUND: The impact of obesity on survival is known to vary in different cancers. Advanced biliary tract cancer was rarely analyzed about the relationship between obesity and prognosis. We performed this study to evaluate the BMI and body weight change as prognostic factors for advanced biliary tract cancer patients with palliative chemotherapy. METHODS: Between January 2005 and December 2016, two hundred and seventy-six patients who underwent chemotherapy for biliary tract cancer were retrospectively analyzed. The relationship between BMI (kg/m2) and clinical outcomes including overall and progression-free survival was assessed. Additionally the relationship between change in body composition and overall survival was evaluated. RESULTS: Median overall survival was 9.7 months for underweight patients, 10.1 months for normal patients, 15.8 months for overweight group, 13.1 months for obese patients, respectively. (p = 0.047) Univariate analysis showed that BMI, stage III, age less than 64 year-old, gallbladder cancer, operation, radiotherapy and ECOG performance were significantly associated with better survival. Compared with normal patients, overweight patients (BMI 23-24.9kg/m2) had a reduced risk of mortality in multivariate analysis (HR 0.632; 95% CI 0.436-0.918, p = 0.016). In the additional analysis for the effect of changes in body weight and BMI to the overall survival, decrease in body weight and BMI (HR 1.410, 95% CI 1.168-1.986, p = 0.046) was associated with a shorter in overall survival. CONCLUSION: Overweight status and the maintenance of body weight during the initial period of chemotherapy are important and independent predictors of better overall survival in advanced biliary tract cancer patients.","Source":"PubMed","category":"HUMAN","training_data":"Body mass index and weight change during initial period of chemotherapy affect survival outcome in advanced biliary tract cancer patients BACKGROUND: The impact of obesity on survival is known to vary in different cancers. Advanced biliary tract cancer was rarely analyzed about the relationship between obesity and prognosis. We performed this study to evaluate the BMI and body weight change as prognostic factors for advanced biliary tract cancer patients with palliative chemotherapy. METHODS: Between January 2005 and December 2016, two hundred and seventy-six patients who underwent chemotherapy for biliary tract cancer were retrospectively analyzed. The relationship between BMI (kg/m2) and clinical outcomes including overall and progression-free survival was assessed. Additionally the relationship between change in body composition and overall survival was evaluated. RESULTS: Median overall survival was 9.7 months for underweight patients, 10.1 months for normal patients, 15.8 months for overweight group, 13.1 months for obese patients, respectively. (p = 0.047) Univariate analysis showed that BMI, stage III, age less than 64 year-old, gallbladder cancer, operation, radiotherapy and ECOG performance were significantly associated with better survival. Compared with normal patients, overweight patients (BMI 23-24.9kg/m2) had a reduced risk of mortality in multivariate analysis (HR 0.632; 95% CI 0.436-0.918, p = 0.016). In the additional analysis for the effect of changes in body weight and BMI to the overall survival, decrease in body weight and BMI (HR 1.410, 95% CI 1.168-1.986, p = 0.046) was associated with a shorter in overall survival. CONCLUSION: Overweight status and the maintenance of body weight during the initial period of chemotherapy are important and independent predictors of better overall survival in advanced biliary tract cancer patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"first clinical data pressurized intraperitoneal aerosol chemotherapy pipac salvage therapy peritoneal metastatic biliary tract cancer background patients suffering peritoneal metastasis biliary tract cancer treated pressurized intraperitoneal aerosol chemotherapy pipac patients methods study carried single institution tertiary referral center certified therapy peritoneal disease retrospective data analysis performed prospective data pipac intra peritoneal low dose doxorubicin 1 5 mg m 2 cisplatin 7 5 mg m 2 delivered intervals 6 weeks outcome criteria microscopic pathological response survival adverse events common terminology criteria adverse events v4 0 results total 13 patients male female 8 5 mean age 58 range 37 75 years underwent 17 pipac procedures without intraoperative complications mean number pipac applications 1 3 range 0 3 due non accessibility abdominal cavity two patients 15 4 rapid clinical deterioration six patients 46 five patients underwent two pipac applications therefore eligible histological analysis assess carcinoma regression overall tumor regression degree determined 4 5 patients overall median survival 85 days 95 confidence interval ci 59 2 110 4 days first pipac application observed complications greater common terminology criteria adverse events v4 0 level 2 occurred conclusion pipac induce objective regression systemic chemotherapy resistant peritoneal metastasis biliary tract cancer however due rapid clinical deterioration patients almost two thirds patients undergo repetitive pipac courses pubmed","probabilities":0.9799733,"Title":"First Clinical Data of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) as Salvage Therapy for Peritoneal Metastatic Biliary Tract Cancer","Abstract":"BACKGROUND: Patients suffering from peritoneal metastasis of biliary tract cancer were treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). PATIENTS AND METHODS: This was a study carried out at a single institution, tertiary referral center certified for therapy of peritoneal disease. Retrospective data analysis was performed of prospective data for PIPAC with intra-peritoneal low-dose doxorubicin (1.5 mg/m(2)) and cisplatin (7.5 mg/m(2)) delivered at intervals of 6 weeks. The outcome criteria were microscopic pathological response, survival, and adverse events [Common Terminology Criteria of Adverse Events (v4.0)]. RESULTS: A total of 13 patients (male/female=8/5) with a mean age of 58 (range=37-75) years underwent 17 PIPAC procedures without intraoperative complications. The mean number of PIPAC applications was 1.3 (range=0-3). Due to non-accessibility of the abdominal cavity in two patients (15.4%) and rapid clinical deterioration in six patients (46%), five patients underwent two or more PIPAC applications and were, therefore, eligible for histological analysis to assess carcinoma regression. Overall tumor regression of any degree was determined in 4/5 patients. An overall median survival of 85 days (95% confidence interval(CI)=59.2-110.4 days) after the first PIPAC application was observed. No complications greater than Common Terminology Criteria of Adverse Events (v4.0) level 2 occurred. CONCLUSION: PIPAC can induce objective regression of systemic chemotherapy-resistant peritoneal metastasis of biliary tract cancer. However, due to a rapid clinical deterioration of the patients, almost two-thirds of the patients cannot undergo repetitive PIPAC courses.","Source":"PubMed","category":"HUMAN","training_data":"First Clinical Data of Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) as Salvage Therapy for Peritoneal Metastatic Biliary Tract Cancer BACKGROUND: Patients suffering from peritoneal metastasis of biliary tract cancer were treated with pressurized intraperitoneal aerosol chemotherapy (PIPAC). PATIENTS AND METHODS: This was a study carried out at a single institution, tertiary referral center certified for therapy of peritoneal disease. Retrospective data analysis was performed of prospective data for PIPAC with intra-peritoneal low-dose doxorubicin (1.5 mg/m(2)) and cisplatin (7.5 mg/m(2)) delivered at intervals of 6 weeks. The outcome criteria were microscopic pathological response, survival, and adverse events [Common Terminology Criteria of Adverse Events (v4.0)]. RESULTS: A total of 13 patients (male/female=8/5) with a mean age of 58 (range=37-75) years underwent 17 PIPAC procedures without intraoperative complications. The mean number of PIPAC applications was 1.3 (range=0-3). Due to non-accessibility of the abdominal cavity in two patients (15.4%) and rapid clinical deterioration in six patients (46%), five patients underwent two or more PIPAC applications and were, therefore, eligible for histological analysis to assess carcinoma regression. Overall tumor regression of any degree was determined in 4/5 patients. An overall median survival of 85 days (95% confidence interval(CI)=59.2-110.4 days) after the first PIPAC application was observed. No complications greater than Common Terminology Criteria of Adverse Events (v4.0) level 2 occurred. CONCLUSION: PIPAC can induce objective regression of systemic chemotherapy-resistant peritoneal metastasis of biliary tract cancer. However, due to a rapid clinical deterioration of the patients, almost two-thirds of the patients cannot undergo repetitive PIPAC courses. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intra ampullary papillary tubular neoplasm iapn characterization tumoral intraepithelial neoplasia occurring within ampulla clinicopathologic analysis 82 cases background uniform terminology systematic analysis mass forming preinvasive neoplasms term tumoral intraepithelial neoplasia occur specifically within ampulla provide detailed analysis neoplasms propose refer intra ampullary papillary tubular neoplasm iapn materials methods three hundred seventeen glandular neoplasms involving ampulla identified review 1469 pancreatoduodenectomies 11 ampullectomies eighty two neoplasms characterized substantial preinvasive exophytic component grew almost exclusively 75 within ampulla ampullary channel intra ampullary portions distal segments common bile duct pancreatic duct analyzed results 1 clinical mean age 64 years male female ratio 2 4 mean tumor size 2 7 cm 2 pathology tumors mixture papillary tubular growth constituting least 25 lesion 57 predominantly 75 papillary 23 predominantly 75 tubular 20 high grade dysplasia present 94 cases 39 showed focal 25 lesion 28 showed substantial 25 75 27 showed extensive 75 high grade dysplasia terms cell lineage morphology 45 mixture patterns however evaluated forced binary approach intestinal int versus gastric pancreatobiliary gpb based predominant pattern 74 classified int 26 gpb 3 immunohistochemistry percent sensitivity specificity cell lineage markers int phenotype muc2 85 78 cdx2 94 61 gbp muc1 89 79 muc5ac 95 69 muc6 83 76 respectively cytokeratin 7 20 coexpressed half 4 invasive carcinoma 64 cases 78 associated invasive carcinoma size tumor amount dysplasia correlated incidence invasion invasive carcinoma int type 58 pancreatobiliary type 42 cell lineage invasive component preinvasive component 84 discrepant cases pancreatobiliary type invasions occurred int type preinvasive lesions 5 outcome overall survival invasive cases significantly worse noninvasive ones 57 vs 93 p 0 01 3 years 69 versus 100 p 0 08 5 years 45 versus 100 p 0 07 respectively compared 166 conventional invasive carcinomas ampullary region invasive iapns significantly better prognosis mean survival 51 versus 31 months p 0 001 3 year survival 69 versus 44 p 0 01 conclusions tumoral intraepithelial neoplasia occurring within ampulla highly analogous pancreatic biliary intraductal papillary tubular neoplasms evidenced papillary tubular growth variable cell lineage spectrum dysplastic change adenoma carcinoma sequence thus propose refer iapn iapns biologically indolent noninvasive examples show excellent prognosis whereas invasion exhibit malignant nevertheless significantly better prognosis typical invasive ampullary carcinomas unaccompanied iapns twenty eight percent 64 230 invasive carcinomas within ampulla arise association iapns stn","probabilities":1.0,"Title":"Intra-Ampullary Papillary-Tubular Neoplasm (Iapn): Characterization Of Tumoral Intraepithelial Neoplasia Occurring Within The Ampulla: A Clinicopathologic Analysis Of 82 Cases","Abstract":"Background: There has been no uniform terminology for systematic analysis of mass-forming preinvasive neoplasms (which we term tumoral intraepithelial neoplasia) that occur specifically within the ampulla. Here, we provide a detailed analysis of these neoplasms, which we propose to refer to as intra-ampullary papillary-tubular neoplasm (IAPN). \r\n\r\n Materials and methods: Three hundred and seventeen glandular neoplasms involving the ampulla were identified through a review of 1469 pancreatoduodenectomies and 11 ampullectomies. Eighty-two neoplasms characterized by substantial preinvasive exophytic component that grew almost exclusively (>75%) within the ampulla (in the ampullary channel or intra-ampullary portions of the very distal segments of the common bile duct or pancreatic duct) were analyzed. \r\n\r\n Results: (1) Clinical: The mean age was 64 years, male/female ratio was 2.4, and mean tumor size was 2.7 cm. (2) Pathology: The tumors had a mixture of both papillary and tubular growth (each constituting at least 25% of the lesion) in 57%; predominantly (>75%) papillary in 23%, and predominantly (>75%) tubular in 20%. High-grade dysplasia was present in 94% of cases, of which 39% showed focal (<25% of the lesion), 28% showed substantial (25% to 75%), and 27% showed extensive (>75%) high-grade dysplasia. In terms of cell-lineage morphology, 45% had a mixture of patterns. However, when evaluated with a forced-binary approach as intestinal (INT) versus gastric/pancreatobiliary (GPB) based on the predominant pattern, 74% were classified as INT and 26% as GPB. (3) Immunohistochemistry: Percent sensitivity/specificity of cell-lineage markers were, for INT phenotype: MUC2 85/78 and CDX2 94/61; and for GBP: MUC1 89/79, MUC5AC 95/69, and MUC6 83/76, respectively. Cytokeratin 7 and 20 were coexpressed in more than half. (4) Invasive carcinoma: In 64 cases (78%), there was an associated invasive carcinoma. Size of the tumor and amount of dysplasia correlated with the incidence of invasion. Invasive carcinoma was of INT-type in 58% and of pancreatobiliary-type in 42%. Cell lineage in the invasive component was the same as that of the preinvasive component in 84%. All discrepant cases were pancreatobiliary-type invasions, which occurred in INT-type preinvasive lesions. (5) OUTCOME: The overall survival of invasive cases were significantly worse than that of noninvasive ones (57% vs. 93%; P=0.01); and 3 years, 69% versus 100% (P=0.08); and 5 years, 45% versus 100% (P=0.07), respectively. When compared with 166 conventional invasive carcinomas of the ampullary region, invasive IAPNs had significantly better prognosis with a mean survival of 51 versus 31 months (P<0.001) and the 3-year survival of 69% versus 44% (P<0.01). \r\n\r\n Conclusions: Tumoral intraepithelial neoplasia occurring within the ampulla are highly analogous to pancreatic or biliary intraductal papillary and tubular neoplasms as evidenced by their papillary and/or tubular growth, variable cell lineage, and spectrum of dysplastic change (adenoma-carcinoma sequence), and thus we propose to refer to these as IAPN. IAPNs are biologically indolent; noninvasive examples show an excellent prognosis, whereas those with invasion exhibit a malignant but nevertheless significantly better prognosis than typical invasive ampullary carcinomas unaccompanied by IAPNs. Twenty eight percent (64 of 230) of invasive carcinomas within the ampulla arise in association with IAPNs.","Source":"STN","category":"HUMAN","training_data":"Intra-Ampullary Papillary-Tubular Neoplasm (Iapn): Characterization Of Tumoral Intraepithelial Neoplasia Occurring Within The Ampulla: A Clinicopathologic Analysis Of 82 Cases Background: There has been no uniform terminology for systematic analysis of mass-forming preinvasive neoplasms (which we term tumoral intraepithelial neoplasia) that occur specifically within the ampulla. Here, we provide a detailed analysis of these neoplasms, which we propose to refer to as intra-ampullary papillary-tubular neoplasm (IAPN). \r\n\r\n Materials and methods: Three hundred and seventeen glandular neoplasms involving the ampulla were identified through a review of 1469 pancreatoduodenectomies and 11 ampullectomies. Eighty-two neoplasms characterized by substantial preinvasive exophytic component that grew almost exclusively (>75%) within the ampulla (in the ampullary channel or intra-ampullary portions of the very distal segments of the common bile duct or pancreatic duct) were analyzed. \r\n\r\n Results: (1) Clinical: The mean age was 64 years, male/female ratio was 2.4, and mean tumor size was 2.7 cm. (2) Pathology: The tumors had a mixture of both papillary and tubular growth (each constituting at least 25% of the lesion) in 57%; predominantly (>75%) papillary in 23%, and predominantly (>75%) tubular in 20%. High-grade dysplasia was present in 94% of cases, of which 39% showed focal (<25% of the lesion), 28% showed substantial (25% to 75%), and 27% showed extensive (>75%) high-grade dysplasia. In terms of cell-lineage morphology, 45% had a mixture of patterns. However, when evaluated with a forced-binary approach as intestinal (INT) versus gastric/pancreatobiliary (GPB) based on the predominant pattern, 74% were classified as INT and 26% as GPB. (3) Immunohistochemistry: Percent sensitivity/specificity of cell-lineage markers were, for INT phenotype: MUC2 85/78 and CDX2 94/61; and for GBP: MUC1 89/79, MUC5AC 95/69, and MUC6 83/76, respectively. Cytokeratin 7 and 20 were coexpressed in more than half. (4) Invasive carcinoma: In 64 cases (78%), there was an associated invasive carcinoma. Size of the tumor and amount of dysplasia correlated with the incidence of invasion. Invasive carcinoma was of INT-type in 58% and of pancreatobiliary-type in 42%. Cell lineage in the invasive component was the same as that of the preinvasive component in 84%. All discrepant cases were pancreatobiliary-type invasions, which occurred in INT-type preinvasive lesions. (5) OUTCOME: The overall survival of invasive cases were significantly worse than that of noninvasive ones (57% vs. 93%; P=0.01); and 3 years, 69% versus 100% (P=0.08); and 5 years, 45% versus 100% (P=0.07), respectively. When compared with 166 conventional invasive carcinomas of the ampullary region, invasive IAPNs had significantly better prognosis with a mean survival of 51 versus 31 months (P<0.001) and the 3-year survival of 69% versus 44% (P<0.01). \r\n\r\n Conclusions: Tumoral intraepithelial neoplasia occurring within the ampulla are highly analogous to pancreatic or biliary intraductal papillary and tubular neoplasms as evidenced by their papillary and/or tubular growth, variable cell lineage, and spectrum of dysplastic change (adenoma-carcinoma sequence), and thus we propose to refer to these as IAPN. IAPNs are biologically indolent; noninvasive examples show an excellent prognosis, whereas those with invasion exhibit a malignant but nevertheless significantly better prognosis than typical invasive ampullary carcinomas unaccompanied by IAPNs. Twenty eight percent (64 of 230) of invasive carcinomas within the ampulla arise in association with IAPNs. STN","prediction_labels":"HUMAN"},{"cleaned":"protein phosphatase phlpp induces cell apoptosis exerts anticancer activity inhibiting survivin phosphorylation nuclear export gallbladder cancer many factors regulate cancer cell apoptosis among survivin strong anti apoptotic effect phlpp tumor suppressor gene induce significant apoptosis however relationship phlpp survivin gallbladder carcinoma gbc reported study found phlpp expression decreased survivin expression increased gbc tissues cell lines expression levels showed inverse relationship associated poor prognosis gbc patients loss phlpp increase level phosphorylated survivin induce nuclear export survivin thus inhibit cell apoptosis promote cell proliferation gbc cells process phlpp regulates survivin phosphorylation intracellular localization involved akt activity re overexpression phlpp gbc cells decrease akt phosphorylation level reduced expression phlpp gbc associated high expression mir 495 increasing phlpp expression inhibiting mir 495 expression induce apoptosis suppress tumor growth gbc xenograft model nude mice results revealed role mechanism phlpp survivin gbc cells proposed strategies gene therapies targeting mir 495 phlpp akt survivin regulatory pathway stn","probabilities":0.9467213,"Title":"Protein Phosphatase Phlpp Induces Cell Apoptosis And Exerts Anticancer Activity By Inhibiting Survivin Phosphorylation And Nuclear Export In Gallbladder Cancer","Abstract":"Many factors regulate cancer cell apoptosis, among which Survivin has a strong anti-apoptotic effect and PHLPP is a tumor suppressor gene that can induce significant apoptosis. However, the relationship between PHLPP and Survivin in gallbladder carcinoma (GBC) has not been reported. This study found that PHLPP expression is decreased and Survivin expression is increased in GBC tissues and cell lines. Their expression levels showed an inverse relationship and were associated with poor prognosis of GBC patients. Loss of PHLPP can increase the level of phosphorylated Survivin and induce the nuclear export of Survivin, which thus inhibit cell apoptosis and promote cell proliferation in GBC cells. The process that PHLPP regulates Survivin phosphorylation and intracellular localization is involved in AKT activity. Re-overexpression of PHLPP in GBC cells can decrease AKT phosphorylation level. Reduced expression of PHLPP in GBC is associated with high expression of miR-495. Increasing PHLPP expression or inhibiting miR-495 expression can induce apoptosis and suppress tumor growth in GBC xenograft model in nude mice. The results revealed the role and mechanism of PHLPP and Survivin in GBC cells and proposed strategies for gene therapies targeting the miR-495 / PHLPP / AKT / Survivin regulatory pathway.","Source":"STN","category":"ANIMAL","training_data":"Protein Phosphatase Phlpp Induces Cell Apoptosis And Exerts Anticancer Activity By Inhibiting Survivin Phosphorylation And Nuclear Export In Gallbladder Cancer Many factors regulate cancer cell apoptosis, among which Survivin has a strong anti-apoptotic effect and PHLPP is a tumor suppressor gene that can induce significant apoptosis. However, the relationship between PHLPP and Survivin in gallbladder carcinoma (GBC) has not been reported. This study found that PHLPP expression is decreased and Survivin expression is increased in GBC tissues and cell lines. Their expression levels showed an inverse relationship and were associated with poor prognosis of GBC patients. Loss of PHLPP can increase the level of phosphorylated Survivin and induce the nuclear export of Survivin, which thus inhibit cell apoptosis and promote cell proliferation in GBC cells. The process that PHLPP regulates Survivin phosphorylation and intracellular localization is involved in AKT activity. Re-overexpression of PHLPP in GBC cells can decrease AKT phosphorylation level. Reduced expression of PHLPP in GBC is associated with high expression of miR-495. Increasing PHLPP expression or inhibiting miR-495 expression can induce apoptosis and suppress tumor growth in GBC xenograft model in nude mice. The results revealed the role and mechanism of PHLPP and Survivin in GBC cells and proposed strategies for gene therapies targeting the miR-495 / PHLPP / AKT / Survivin regulatory pathway. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic significance preoperative neutrophil lymphocyte ratio platelet lymphocyte ratio patients gallbladder carcinoma purpose neutrophil lymphocyte ratio nlr platelet lymphocyte ratio plr immune response related indicators preoperative nlr plr considered related prognosis various cancers objective study evaluate prognostic significance nlr plr patients gallbladder carcinoma gbc methods 2001 2013 145 patients gbc recruited retrospective study cutoff values nlr plr determined receiver operating characteristic curves roc correlation clinical data including tumor differentiation nevin stage tnm stage operation margin operation mode nlr plr hemoglobin c reactive protein crp carcinoembryonic antigen cea carbohydrate antigen 199 ca199 median survival period patients analyzed univariate survival analysis multivariate prognosis analysis performed select independent prognostic factors results cutoff values nlr plr 1 94 113 34 respectively compared low nlr low plr group 5 year survival rates high nlr high plr group reduced p 0 05 degree tumor differentiation nevin stage tnm stage operation mode nlr plr ca199 total bilirubin crp cea associated median survival period patients p 0 01 multivariate prognosis analysis showed nlr nevin stage operation mode hemoglobin independent prognostic factors p 0 05 conclusion preoperative nlr plr closely related prognosis patients gbc might useful evaluation prognosis patients gbc pubmed","probabilities":0.9799733,"Title":"Prognostic significance of preoperative neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in patients with gallbladder carcinoma","Abstract":"PURPOSE: Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were immune response-related indicators. Preoperative NLR and PLR had been considered to be related to the prognosis of various cancers. The objective of this study was to evaluate the prognostic significance of NLR and PLR in patients with gallbladder carcinoma (GBC). METHODS: From 2001 to 2013, 145 patients with GBC were recruited in this retrospective study. Cutoff values of NLR and PLR were determined by receiver operating characteristic curves (ROC). The correlation of clinical data, including tumor differentiation, nevin stage, TNM stage, operation margin, operation mode, NLR, PLR, hemoglobin, C reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) with median survival period of patients was analyzed by univariate survival analysis. The multivariate prognosis analysis was performed to select the independent prognostic factors. RESULTS: The cutoff values of NLR and PLR were 1.94 and 113.34, respectively. Compared with low NLR and low PLR group, the 5-year survival rates in high NLR and high PLR group were reduced (P < 0.05). The degree of tumor differentiation, nevin stage, TNM stage, operation mode, NLR, PLR, CA199, total bilirubin, CRP and CEA were associated with the median survival period of patients (P < 0.01). The multivariate prognosis analysis showed that NLR, nevin stage, operation mode and hemoglobin were independent prognostic factors (P < 0.05). CONCLUSION: Preoperative NLR and PLR were closely related to prognosis of patients with GBC and might be useful for the evaluation of prognosis of patients with GBC.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of preoperative neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in patients with gallbladder carcinoma PURPOSE: Neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) were immune response-related indicators. Preoperative NLR and PLR had been considered to be related to the prognosis of various cancers. The objective of this study was to evaluate the prognostic significance of NLR and PLR in patients with gallbladder carcinoma (GBC). METHODS: From 2001 to 2013, 145 patients with GBC were recruited in this retrospective study. Cutoff values of NLR and PLR were determined by receiver operating characteristic curves (ROC). The correlation of clinical data, including tumor differentiation, nevin stage, TNM stage, operation margin, operation mode, NLR, PLR, hemoglobin, C reactive protein (CRP), carcinoembryonic antigen (CEA), and carbohydrate antigen 199 (CA199) with median survival period of patients was analyzed by univariate survival analysis. The multivariate prognosis analysis was performed to select the independent prognostic factors. RESULTS: The cutoff values of NLR and PLR were 1.94 and 113.34, respectively. Compared with low NLR and low PLR group, the 5-year survival rates in high NLR and high PLR group were reduced (P < 0.05). The degree of tumor differentiation, nevin stage, TNM stage, operation mode, NLR, PLR, CA199, total bilirubin, CRP and CEA were associated with the median survival period of patients (P < 0.01). The multivariate prognosis analysis showed that NLR, nevin stage, operation mode and hemoglobin were independent prognostic factors (P < 0.05). CONCLUSION: Preoperative NLR and PLR were closely related to prognosis of patients with GBC and might be useful for the evaluation of prognosis of patients with GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value carbohydrate antigen 19 9 patients undergoing resection biliary tract cancer background clinical significance abnormally high levels carbohydrate antigen ca 19 9 resection biliary tract cancer btc well established aim study determine prognostic value ca19 9 normalization patients undergoing resection btc curative intent methods patients btc undergoing resection curative intent 1996 2015 divided normal preoperative ca19 9 level normal ca19 9 group abnormally high preoperative ca19 9 level 37 units ml normal postoperative ca19 9 level normalization group abnormally high preoperative ca19 9 level abnormally high postoperative ca19 9 level non normalization group overall survival os analysed predictors os determined results normal ca19 9 group 180 patients normalization group 74 better os non normalization group 58 3 year os rate 70 4 73 31 per cent respectively p 0 001 normal ca19 9 normalization groups equivalent os p 0 880 multivariable analysis factors associated worse os lymph node metastases hazard ratio hr 1 78 p 0 014 abnormally high postoperative ca19 9 level hr 3 16 p 0 001 normalization group os differ r0 versus r1 resection 3 year os rate 69 versus 62 per cent respectively p 0 372 non normalization group patients r1 resection worse os 3 year os rate 36 20 per cent r0 r1 respectively p 0 032 conclusion non normalization ca19 9 level resection btc curative intent associated worse os r1 resection associated particularly poor prognosis ca19 9 levels normalize pubmed","probabilities":0.9799733,"Title":"Prognostic value of carbohydrate antigen 19-9 in patients undergoing resection of biliary tract cancer","Abstract":"BACKGROUND: The clinical significance of abnormally high levels of carbohydrate antigen (CA) 19-9 after resection of biliary tract cancer (BTC) is not well established. The aim of this study was to determine the prognostic value of CA19-9 normalization in patients undergoing resection of BTC with curative intent. METHODS: Patients with BTC undergoing resection with curative intent (1996-2015) were divided into those with normal preoperative CA19-9 level (normal CA19-9 group), those with an abnormally high preoperative CA19-9 level (over 37 units/ml) and normal postoperative CA19-9 level (normalization group), and those with an abnormally high preoperative CA19-9 level and abnormally high postoperative CA19-9 level (non-normalization group). Overall survival (OS) was analysed and predictors of OS were determined. RESULTS: The normal CA19-9 group (180 patients) and normalization group (74) had better OS than the non-normalization group (58) (3-year OS rate 70·4, 73 and 31 per cent respectively; both P < 0·001). The normal CA19-9 and normalization groups had equivalent OS (P = 0·880). On multivariable analysis, factors associated with worse OS were lymph node metastases (hazard ratio (HR) 1·78; P = 0·014) and abnormally high postoperative CA19-9 level (HR 3·16; P < 0·001). In the normalization group, OS did not differ after R0 versus R1 resection (3-year OS rate 69 versus 62 per cent respectively; P = 0·372); in the non-normalization group, patients with R1 resection had worse OS (3-year OS rate 36 and 20 per cent for R0 and R1 respectively; P = 0·032). CONCLUSION: Non-normalization of CA19-9 level after resection of BTC with curative intent was associated with worse OS. R1 resection was associated with a particularly poor prognosis when CA19-9 levels did not normalize.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic value of carbohydrate antigen 19-9 in patients undergoing resection of biliary tract cancer BACKGROUND: The clinical significance of abnormally high levels of carbohydrate antigen (CA) 19-9 after resection of biliary tract cancer (BTC) is not well established. The aim of this study was to determine the prognostic value of CA19-9 normalization in patients undergoing resection of BTC with curative intent. METHODS: Patients with BTC undergoing resection with curative intent (1996-2015) were divided into those with normal preoperative CA19-9 level (normal CA19-9 group), those with an abnormally high preoperative CA19-9 level (over 37 units/ml) and normal postoperative CA19-9 level (normalization group), and those with an abnormally high preoperative CA19-9 level and abnormally high postoperative CA19-9 level (non-normalization group). Overall survival (OS) was analysed and predictors of OS were determined. RESULTS: The normal CA19-9 group (180 patients) and normalization group (74) had better OS than the non-normalization group (58) (3-year OS rate 70·4, 73 and 31 per cent respectively; both P < 0·001). The normal CA19-9 and normalization groups had equivalent OS (P = 0·880). On multivariable analysis, factors associated with worse OS were lymph node metastases (hazard ratio (HR) 1·78; P = 0·014) and abnormally high postoperative CA19-9 level (HR 3·16; P < 0·001). In the normalization group, OS did not differ after R0 versus R1 resection (3-year OS rate 69 versus 62 per cent respectively; P = 0·372); in the non-normalization group, patients with R1 resection had worse OS (3-year OS rate 36 and 20 per cent for R0 and R1 respectively; P = 0·032). CONCLUSION: Non-normalization of CA19-9 level after resection of BTC with curative intent was associated with worse OS. R1 resection was associated with a particularly poor prognosis when CA19-9 levels did not normalize. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value c met expression cholangiocarcinoma aim explore relationship clinicopathological features proteins c met expression prognosis cholangiocarcinoma methods clinical data completed follow information patients cholangiocarcinoma underwent cholangiocarcinoma operation january 2004 december 2010 analyzed retrospectively relationship clinicopathological features c met prognosis patients analyzed results patients high expression c met significantly shorter overall survival low expression c met difference statistically significant p 003 patients high c met expression significantly shorter disease free survival time low expression c met difference statistically significant p 009 cox multivariate analysis high c met expression tumor tissues independent risk factor predicting overall survival disease free survival patients cholangiocarcinoma p 038 048 relative risk 1 390 1 427 conclusion patients high c met expression cancer tissues shorter disease free survival overall survival high expression c met independent risk factor overall survival disease free survival pubmed","probabilities":0.88235295,"Title":"Prognostic Value of C-met Expression in Cholangiocarcinoma","Abstract":"AIM: To explore the relationship of clinicopathological features and the proteins of C-met expression in the prognosis of cholangiocarcinoma. METHODS: Clinical data and the completed follow-up information of patients with cholangiocarcinoma who underwent cholangiocarcinoma operation from January 2004 to December 2010 were analyzed retrospectively. The relationship of clinicopathological features and C-met in the prognosis of the patients was analyzed. RESULTS: Patients with high expression of C-met had significantly shorter overall survival than those with low expression of C-met, the difference being statistically significant (P = .003). Patients with high C-met expression had significantly shorter disease-free survival time than those with low expression of C-met, the difference being statistically significant (P = .009). By COX multivariate analysis, high C-met expression in tumor tissues was an independent risk factor in predicting overall survival and disease-free survival for patients with cholangiocarcinoma (P = .038, .048, relative risk = 1.390, 1.427). CONCLUSION: Patients with high C-met expression in cancer tissues had shorter disease-free survival and overall survival. High expression of C-met is an independent risk factor for overall survival and disease-free survival.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Value of C-met Expression in Cholangiocarcinoma AIM: To explore the relationship of clinicopathological features and the proteins of C-met expression in the prognosis of cholangiocarcinoma. METHODS: Clinical data and the completed follow-up information of patients with cholangiocarcinoma who underwent cholangiocarcinoma operation from January 2004 to December 2010 were analyzed retrospectively. The relationship of clinicopathological features and C-met in the prognosis of the patients was analyzed. RESULTS: Patients with high expression of C-met had significantly shorter overall survival than those with low expression of C-met, the difference being statistically significant (P = .003). Patients with high C-met expression had significantly shorter disease-free survival time than those with low expression of C-met, the difference being statistically significant (P = .009). By COX multivariate analysis, high C-met expression in tumor tissues was an independent risk factor in predicting overall survival and disease-free survival for patients with cholangiocarcinoma (P = .038, .048, relative risk = 1.390, 1.427). CONCLUSION: Patients with high C-met expression in cancer tissues had shorter disease-free survival and overall survival. High expression of C-met is an independent risk factor for overall survival and disease-free survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence predictors lymph nodal metastases patients perihilar cholangiocarcinoma background aim lymph node metastasis major prognostic factor perihilar cholangiocarcinoma phc however prognostic significance extent node dissection lymph node ratio lnr number location positive nodes remain unclear aimed evaluate whether node status lnr number location positive nodes independent factors staging phc determine minimum requirements node examination methods surveillance epidemiology end results database used identify 1116 resected phcs 1998 2008 correlation nodal status survival analyzed retrospectively results lymph node metastasis occurred 43 4 patients independent predictor overall survival cancer specific survival survival benefit observed increasing number node retrieval node positive patients however node negative patients 13 node dissection survival benefit 3 total lymph node count tlnc 12 tlnc 3 5 year overall survival 52 8 vs 39 7 vs 26 3 p 0 001 5 year cancer specific survival 60 6 vs 46 3 vs 30 0 p 0 001 difference survival patients regional distant node involvement found survival patients greater three positive nodes significantly worse three less relative ratio 1 466 p 0 001 patients lnr 0 27 also unfavorable prognosis relative ratio 1 376 p 0 001 conclusions determined adequately assess nodal status life threatening disease 13 nodes retrieval considered number positive nodes lnr rather location metastatic nodes may defined parameters staging phc stn","probabilities":0.9799733,"Title":"Incidence And Predictors Of Lymph Nodal Metastases In Patients With Perihilar Cholangiocarcinoma","Abstract":"Background and aim: Lymph node metastasis is a major prognostic factor for perihilar cholangiocarcinoma (PHC). However, prognostic significance of extent of node dissection, lymph node ratio (LNR), and number and location of positive nodes remain unclear. We aimed to evaluate whether node status, LNR, or number or location of positive nodes are independent factors for staging in PHC and to determine the minimum requirements for node examination. \r\n\r\n Methods: The Surveillance, Epidemiology, and End Results database was used to identify 1116 resected PHCs from 1998 to 2008. The correlation between nodal status and survival was analyzed retrospectively. \r\n\r\n Results: Lymph node metastasis occurred in 43.4% patients and was an independent predictor for overall survival and cancer-specific survival. No survival benefit was observed for an increasing number of node retrieval in node-positive patients. However, in node-negative patients, ≥13 node dissection was of more survival benefit than 3 ≤ total lymph node count (TLNC) ≤ 12 and TLNC < 3 (5-year overall survival: 52.8% vs 39.7% vs 26.3%, P = 0.001; 5-year cancer-specific survival: 60.6% vs 46.3% vs 30.0%, P = 0.001). No difference in survival between patients with regional and distant node involvement was found. Survival for patients with greater than three positive nodes was significantly worse than that for those with three or less (relative ratio: 1.466, P = 0.001). And patients with LNR > 0.27 also had unfavorable prognosis (relative ratio: 1.376, P = 0.001). \r\n\r\n Conclusions: We determined that to adequately assess nodal status of this life-threatening disease, 13 or more nodes retrieval should be considered. Number of positive nodes and LNR rather than location of metastatic nodes may be defined as parameters for staging of PHC.","Source":"STN","category":"HUMAN","training_data":"Incidence And Predictors Of Lymph Nodal Metastases In Patients With Perihilar Cholangiocarcinoma Background and aim: Lymph node metastasis is a major prognostic factor for perihilar cholangiocarcinoma (PHC). However, prognostic significance of extent of node dissection, lymph node ratio (LNR), and number and location of positive nodes remain unclear. We aimed to evaluate whether node status, LNR, or number or location of positive nodes are independent factors for staging in PHC and to determine the minimum requirements for node examination. \r\n\r\n Methods: The Surveillance, Epidemiology, and End Results database was used to identify 1116 resected PHCs from 1998 to 2008. The correlation between nodal status and survival was analyzed retrospectively. \r\n\r\n Results: Lymph node metastasis occurred in 43.4% patients and was an independent predictor for overall survival and cancer-specific survival. No survival benefit was observed for an increasing number of node retrieval in node-positive patients. However, in node-negative patients, ≥13 node dissection was of more survival benefit than 3 ≤ total lymph node count (TLNC) ≤ 12 and TLNC < 3 (5-year overall survival: 52.8% vs 39.7% vs 26.3%, P = 0.001; 5-year cancer-specific survival: 60.6% vs 46.3% vs 30.0%, P = 0.001). No difference in survival between patients with regional and distant node involvement was found. Survival for patients with greater than three positive nodes was significantly worse than that for those with three or less (relative ratio: 1.466, P = 0.001). And patients with LNR > 0.27 also had unfavorable prognosis (relative ratio: 1.376, P = 0.001). \r\n\r\n Conclusions: We determined that to adequately assess nodal status of this life-threatening disease, 13 or more nodes retrieval should be considered. Number of positive nodes and LNR rather than location of metastatic nodes may be defined as parameters for staging of PHC. STN","prediction_labels":"HUMAN"},{"cleaned":"coffee cancer risk summary overview reviewed available evidence coffee drinking risk cancers selected cancers updated may 2016 coffee consumption associated overall cancer risk meta analysis reported pooled relative risk rr increment 1 cup coffee day 1 00 95 confidence interval ci 0 99 1 01 cancers coffee drinking associated reduced risk liver cancer meta analysis cohort studies found rr increment consumption 1 cup day 0 85 95 ci 0 81 0 90 liver cancer favorable effect liver enzymes cirrhosis another meta analysis showed inverse relation endometrial cancer risk rr 0 92 95 ci 0 88 0 96 increment 1 cup day possible decreased risk found studies oral pharyngeal cancer advanced prostate cancer although data mixed overall seems favorable effect coffee drinking colorectal cancer case control studies absence consistent relation cohort studies bladder cancer results consistent however possible direct association dose duration related might depend residual confounding effect smoking studies suggest increased risk childhood leukemia maternal coffee drinking pregnancy data limited inconsistent although results studies mixed overall evidence suggests association coffee intake cancers stomach pancreas lung breast ovary prostate overall data limited rr close unity neoplasms including esophagus small intestine gallbladder biliary tract skin kidney brain thyroid well soft tissue sarcoma lymphohematopoietic cancer pubmed","probabilities":0.7966102,"Title":"Coffee and cancer risk: a summary overview","Abstract":"We reviewed available evidence on coffee drinking and the risk of all cancers and selected cancers updated to May 2016. Coffee consumption is not associated with overall cancer risk. A meta-analysis reported a pooled relative risk (RR) for an increment of 1 cup of coffee/day of 1.00 [95% confidence interval (CI): 0.99-1.01] for all cancers. Coffee drinking is associated with a reduced risk of liver cancer. A meta-analysis of cohort studies found an RR for an increment of consumption of 1 cup/day of 0.85 (95% CI: 0.81-0.90) for liver cancer and a favorable effect on liver enzymes and cirrhosis. Another meta-analysis showed an inverse relation for endometrial cancer risk, with an RR of 0.92 (95% CI: 0.88-0.96) for an increment of 1 cup/day. A possible decreased risk was found in some studies for oral/pharyngeal cancer and for advanced prostate cancer. Although data are mixed, overall, there seems to be some favorable effect of coffee drinking on colorectal cancer in case-control studies, in the absence of a consistent relation in cohort studies. For bladder cancer, the results are not consistent; however, any possible direct association is not dose and duration related, and might depend on a residual confounding effect of smoking. A few studies suggest an increased risk of childhood leukemia after maternal coffee drinking during pregnancy, but data are limited and inconsistent. Although the results of studies are mixed, the overall evidence suggests no association of coffee intake with cancers of the stomach, pancreas, lung, breast, ovary, and prostate overall. Data are limited, with RR close to unity for other neoplasms, including those of the esophagus, small intestine, gallbladder and biliary tract, skin, kidney, brain, thyroid, as well as for soft tissue sarcoma and lymphohematopoietic cancer.","Source":"PubMed","category":"HUMAN","training_data":"Coffee and cancer risk: a summary overview We reviewed available evidence on coffee drinking and the risk of all cancers and selected cancers updated to May 2016. Coffee consumption is not associated with overall cancer risk. A meta-analysis reported a pooled relative risk (RR) for an increment of 1 cup of coffee/day of 1.00 [95% confidence interval (CI): 0.99-1.01] for all cancers. Coffee drinking is associated with a reduced risk of liver cancer. A meta-analysis of cohort studies found an RR for an increment of consumption of 1 cup/day of 0.85 (95% CI: 0.81-0.90) for liver cancer and a favorable effect on liver enzymes and cirrhosis. Another meta-analysis showed an inverse relation for endometrial cancer risk, with an RR of 0.92 (95% CI: 0.88-0.96) for an increment of 1 cup/day. A possible decreased risk was found in some studies for oral/pharyngeal cancer and for advanced prostate cancer. Although data are mixed, overall, there seems to be some favorable effect of coffee drinking on colorectal cancer in case-control studies, in the absence of a consistent relation in cohort studies. For bladder cancer, the results are not consistent; however, any possible direct association is not dose and duration related, and might depend on a residual confounding effect of smoking. A few studies suggest an increased risk of childhood leukemia after maternal coffee drinking during pregnancy, but data are limited and inconsistent. Although the results of studies are mixed, the overall evidence suggests no association of coffee intake with cancers of the stomach, pancreas, lung, breast, ovary, and prostate overall. Data are limited, with RR close to unity for other neoplasms, including those of the esophagus, small intestine, gallbladder and biliary tract, skin, kidney, brain, thyroid, as well as for soft tissue sarcoma and lymphohematopoietic cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect statins risk extrahepatic cholangiocarcinoma background statins proven cytotoxic human cholangiocarcinoma cells inhibiting cell division inducing apoptosis aimed determine effect statin use risk cancer development survival patients extrahepatic cholangiocarcinoma ecc including perihilar cholangiocarcinoma pcca distal cholangiocarcinoma dcca methods 394 patients ecc hyperlipidemia received care mayo clinic rochester 2005 2015 matched age sex race ethnicity residency 788 controls hyperlipidemia clinical outcome data abstracted odds ratios risk hazard ratios outcomes calculated results mean age standard deviation sd cases controls 65 6 years 13 8 number statin users cases controls 73 19 403 51 respectively hepatitis c virus infection 15 84 95 ci 4 06 61 87 p 0 001 significant risk factor pcca followed inflammatory bowel disease cirrhosis whereas liver diseases including biliary stone disease 4 06 2 24 7 36 p 0 001 significant risk factor dcca statin use associated significantly reduced risk ecc 0 22 0 16 029 well subtypes pcca 0 3 0 21 0 41 dcca 0 06 0 03 0 14 p 0 0001 moderate intensity dosage found decrease risk ecc 0 48 0 34 0 67 p 0 001 comparing statin ever users non users dcca patients used statins significantly overall better survival hr 0 53 0 29 0 97 p 0 04 conclusion case control study suggests statins decrease risk extrahepatic cholangiocarcinoma may improve survival patients dcca additional validation studies warranted stn","probabilities":0.9467213,"Title":"Effect Of Statins On The Risk Of Extrahepatic Cholangiocarcinoma","Abstract":"Background: Statins have been proven to be cytotoxic to human cholangiocarcinoma cells by inhibiting cell division and inducing apoptosis. We aimed to determine the effect of statin use on the risk of cancer development and survival in patients with extrahepatic cholangiocarcinoma (ECC) including perihilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA). \r\n\r\n Methods: 394 patients with ECC and hyperlipidemia who received care at Mayo Clinic Rochester between 2005 and 2015 were matched by age, sex, race, ethnicity and residency to 788 controls with hyperlipidemia. Clinical and outcome data was abstracted. The odds ratios for risk and hazard ratios for outcomes were calculated. \r\n\r\n Results: The mean age and standard deviation (SD) for cases and controls was 65.6 years (13.8). The number of statin users in cases and controls were 73 (19%) and 403 (51%), respectively. Hepatitis C virus infection (OR=15.84, 95% CI 4.06-61.87; p<0.001) was the most significant risk factor for pCCA followed by inflammatory bowel disease and cirrhosis, whereas other liver diseases including biliary stone disease (OR=4.06, 2.24-7.36; p<0.001) was the only significant risk factor for dCCA. Statin use was associated with significantly reduced risk for all ECC (OR=0.22, 0.16-029) as well as for the subtypes pCCA (OR=0.3, 0.21-0.41) and dCCA (OR=0.06, 0.03-0.14) all p<0.0001. Moderate intensity dosage was found to decrease the risk of ECC (OR=0.48, 0.34-0.67, p<0.001). Comparing statin ever users to non-users, dCCA patients who used statins had significantly overall better survival (HR=0.53, 0.29-0.97, p=0.04). \r\n\r\n Conclusion: This case-control study suggests that statins decrease the risk of extrahepatic cholangiocarcinoma and may improve survival in patients with dCCA. Additional validation studies are warranted.","Source":"STN","category":"HUMAN","training_data":"Effect Of Statins On The Risk Of Extrahepatic Cholangiocarcinoma Background: Statins have been proven to be cytotoxic to human cholangiocarcinoma cells by inhibiting cell division and inducing apoptosis. We aimed to determine the effect of statin use on the risk of cancer development and survival in patients with extrahepatic cholangiocarcinoma (ECC) including perihilar cholangiocarcinoma (pCCA) and distal cholangiocarcinoma (dCCA). \r\n\r\n Methods: 394 patients with ECC and hyperlipidemia who received care at Mayo Clinic Rochester between 2005 and 2015 were matched by age, sex, race, ethnicity and residency to 788 controls with hyperlipidemia. Clinical and outcome data was abstracted. The odds ratios for risk and hazard ratios for outcomes were calculated. \r\n\r\n Results: The mean age and standard deviation (SD) for cases and controls was 65.6 years (13.8). The number of statin users in cases and controls were 73 (19%) and 403 (51%), respectively. Hepatitis C virus infection (OR=15.84, 95% CI 4.06-61.87; p<0.001) was the most significant risk factor for pCCA followed by inflammatory bowel disease and cirrhosis, whereas other liver diseases including biliary stone disease (OR=4.06, 2.24-7.36; p<0.001) was the only significant risk factor for dCCA. Statin use was associated with significantly reduced risk for all ECC (OR=0.22, 0.16-029) as well as for the subtypes pCCA (OR=0.3, 0.21-0.41) and dCCA (OR=0.06, 0.03-0.14) all p<0.0001. Moderate intensity dosage was found to decrease the risk of ECC (OR=0.48, 0.34-0.67, p<0.001). Comparing statin ever users to non-users, dCCA patients who used statins had significantly overall better survival (HR=0.53, 0.29-0.97, p=0.04). \r\n\r\n Conclusion: This case-control study suggests that statins decrease the risk of extrahepatic cholangiocarcinoma and may improve survival in patients with dCCA. Additional validation studies are warranted. STN","prediction_labels":"ANIMAL"},{"cleaned":"impact adjuvant chemotherapy pancreaticoduodenectomy distal cholangiocarcinoma propensity score analysis french multicentric cohort background benefit adjuvant chemotherapy ac pancreaticoduodenectomy pd distal cholangiocarcinoma dcc remains controversial study aimed evaluate impact ac pd dcc large multicentric cohort methods patients five french centers underwent pd dcc 2000 2015 received ac ac group surgery ac group included analysis variables associated ac administration analyzed univariate analysis cox regression identified covariates associated overall survival os disease free survival dfs ac cohort matched ac cohort 1 1 propensity score ps based likelihood ac administrateion independent factors associated decreased os dfs results 178 patients included 56 31 5 received ac whole cohort difference os dfs ac ac groups identified p 0 15 p 0 07 respectively ps matching ac group n 49 comparable ac group n 49 factors associated ac administration factors associated decreased survival large cohort matching medians os dfs ac group ac group comparable 26 27 vs 43 33 months p 0 34 15 47 vs 14 70 months p 0 79 respectively conclusion study demonstrate survival benefit adjuvant chemotherapy mostly base gemcitabine regimen dcc pd even propensity score matching new trial specially designed dcc urgently needed improve survival surgical resection pubmed","probabilities":0.9799733,"Title":"Impact of adjuvant chemotherapy after pancreaticoduodenectomy for distal cholangiocarcinoma: a propensity score analysis from a French multicentric cohort","Abstract":"BACKGROUND: The benefit of adjuvant chemotherapy (AC) after pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) remains controversial. The study aimed to evaluate the impact of AC after PD for DCC in a large multicentric cohort. METHODS: Patients from five French centers who underwent from PD for DCC between 2000 and 2015 and received AC (AC+ group) or surgery only (AC- group) were included in the analysis. Variables associated with AC administration were analyzed by univariate analysis. The Cox regression identified covariates associated with overall survival (OS) and disease-free survival (DFS). The AC+ cohort was matched to the AC- cohort (1:1) by a propensity score (PS) based on the likelihood of AC administratEion and independent factors associated with decreased OS and DFS. RESULTS: Of the 178 patients included, 56 (31.5%) received AC. In the whole cohort, no difference on OS and DFS between the AC+ and AC- groups was identified (P = 0.15 and P = 0.07, respectively). After PS matching, the AC+ group (n = 49) was comparable to the AC- group (n = 49) on factors associated with AC administration and on factors associated with a decreased survival in the large cohort. After matching, the medians of OS and DFS in the AC+ group and in the AC- group were comparable (26.27 vs 43.33 months, P = 0.34, and 15.47 vs. 14.70 months, P = 0.79, respectively). CONCLUSION: Our study did not demonstrate a survival benefit of adjuvant chemotherapy (mostly base on gemcitabine regimen) for DCC after PD even after propensity score matching. New trial specially designed for DCC is urgently needed to improve survival after surgical resection.","Source":"PubMed","category":"HUMAN","training_data":"Impact of adjuvant chemotherapy after pancreaticoduodenectomy for distal cholangiocarcinoma: a propensity score analysis from a French multicentric cohort BACKGROUND: The benefit of adjuvant chemotherapy (AC) after pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) remains controversial. The study aimed to evaluate the impact of AC after PD for DCC in a large multicentric cohort. METHODS: Patients from five French centers who underwent from PD for DCC between 2000 and 2015 and received AC (AC+ group) or surgery only (AC- group) were included in the analysis. Variables associated with AC administration were analyzed by univariate analysis. The Cox regression identified covariates associated with overall survival (OS) and disease-free survival (DFS). The AC+ cohort was matched to the AC- cohort (1:1) by a propensity score (PS) based on the likelihood of AC administratEion and independent factors associated with decreased OS and DFS. RESULTS: Of the 178 patients included, 56 (31.5%) received AC. In the whole cohort, no difference on OS and DFS between the AC+ and AC- groups was identified (P = 0.15 and P = 0.07, respectively). After PS matching, the AC+ group (n = 49) was comparable to the AC- group (n = 49) on factors associated with AC administration and on factors associated with a decreased survival in the large cohort. After matching, the medians of OS and DFS in the AC+ group and in the AC- group were comparable (26.27 vs 43.33 months, P = 0.34, and 15.47 vs. 14.70 months, P = 0.79, respectively). CONCLUSION: Our study did not demonstrate a survival benefit of adjuvant chemotherapy (mostly base on gemcitabine regimen) for DCC after PD even after propensity score matching. New trial specially designed for DCC is urgently needed to improve survival after surgical resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumor necrosis infiltrating macrophages predict survival curative resection cholangiocarcinoma background tumor necrosis well tumor associated macrophages tams tumor invasive front tif suggested prognostic value selected solid tumors inclusive hilar cholangiocarcinoma however little known regarding influence tumor progression prognosis intrahepatic cholangiocarcinoma icc methods analyzed surgically resected tumor specimens human icc n 88 distribution localization tams defined expression cd68 formation necrosis extent peritumoral fibrosis abundance tams tumor necrosis grade fibrosis assessed immunohistochemically histologically correlated clinicopathological characteristics tumor recurrence patients survival statistical analysis performed using spss software results patients tumors characterized low levels tams tif necrosis showed significantly decreased 1 3 5 y recurrence free survival significantly decreased overall survival compared patients tumors showing high levels tams tif necrosis patients high density tams tif showed significantly lower incidence tumor recurrence well p 0 05 absence tumor necrosis tams tif confirmed independent prognostic variables multivariate survival analysis p 0 05 conclusions high levels tams tif absence histologic tumor necrosis associated significantly improved recurrence free overall survival patients icc results suggest tams necrosis valuable prognostic markers routine histopathologic evaluation might indicate individualized therapeutic strategies stn","probabilities":0.8333333,"Title":"Tumor Necrosis And Infiltrating Macrophages Predict Survival After Curative Resection For Cholangiocarcinoma","Abstract":"Background. Tumor necrosis as well as tumor-associated macrophages (TAMs) in the tumor invasive front (TIF) have been suggested to have a prognostic value in selected solid tumors, inclusive hilar cholangiocarcinoma. However, little is known regarding their influence on tumor progression and prognosis in intrahepatic cholangiocarcinoma (iCC). Methods. We analyzed surgically resected tumor specimens of human iCC (n = 88) for distribution and localization of TAMs, as defined by expression of CD68, formation of necrosis and extent of peritumoral fibrosis. Abundance of TAMs, tumor necrosis and grade of fibrosis were assessed immunohistochemically and histologically and correlated with clinicopathological characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software. Results. Patients with tumors characterized by low levels of TAMs in TIF or necrosis showed a significantly decreased 1-, 3- and 5-y recurrence-free survival and a significantly decreased overall survival, when compared with patients with tumors showing high levels of TAMs in TIF or no necrosis. Patients with high density of TAMs in TIF showed significantly lower incidence of tumor recurrence, as well (p < 0.05). Absence of tumor necrosis and TAMs in TIF were confirmed as independent prognostic variables in the multivariate survival analysis (all p < 0.05). Conclusions. High levels of TAMs in TIF or absence of histologic tumor necrosis are associated with a significantly improved recurrence-free and overall survival of patients with iCC. These results suggest TAMs and necrosis as valuable prognostic markers in routine histopathologic evaluation, and might indicate more individualized therapeutic strategies.","Source":"STN","category":"HUMAN","training_data":"Tumor Necrosis And Infiltrating Macrophages Predict Survival After Curative Resection For Cholangiocarcinoma Background. Tumor necrosis as well as tumor-associated macrophages (TAMs) in the tumor invasive front (TIF) have been suggested to have a prognostic value in selected solid tumors, inclusive hilar cholangiocarcinoma. However, little is known regarding their influence on tumor progression and prognosis in intrahepatic cholangiocarcinoma (iCC). Methods. We analyzed surgically resected tumor specimens of human iCC (n = 88) for distribution and localization of TAMs, as defined by expression of CD68, formation of necrosis and extent of peritumoral fibrosis. Abundance of TAMs, tumor necrosis and grade of fibrosis were assessed immunohistochemically and histologically and correlated with clinicopathological characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software. Results. Patients with tumors characterized by low levels of TAMs in TIF or necrosis showed a significantly decreased 1-, 3- and 5-y recurrence-free survival and a significantly decreased overall survival, when compared with patients with tumors showing high levels of TAMs in TIF or no necrosis. Patients with high density of TAMs in TIF showed significantly lower incidence of tumor recurrence, as well (p < 0.05). Absence of tumor necrosis and TAMs in TIF were confirmed as independent prognostic variables in the multivariate survival analysis (all p < 0.05). Conclusions. High levels of TAMs in TIF or absence of histologic tumor necrosis are associated with a significantly improved recurrence-free and overall survival of patients with iCC. These results suggest TAMs and necrosis as valuable prognostic markers in routine histopathologic evaluation, and might indicate more individualized therapeutic strategies. STN","prediction_labels":"HUMAN"},{"cleaned":"high grade intraductal papillary neoplasm prognostic marker intrahepatic cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"High-Grade Intraductal Papillary Neoplasm As A Prognostic Marker In Intrahepatic Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"High-Grade Intraductal Papillary Neoplasm As A Prognostic Marker In Intrahepatic Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"comparison choi criteria response evaluation criteria solid tumors recist intrahepatic cholangiocarcinoma treated glass microspheres yttrium 90 selective internal radiation therapy sirt objective compare choi criteria response evaluation criteria solid tumors recist prediction overall survival os patients treated glass microspheres yttrium 90 selective internal radiation therapy sirt intrahepatic cholangiocarcinoma icc methods 2010 2014 45 adult patients locally advanced icc treated sirt retrospectively analyzed computed tomography scans performed treatment analyzed using recist 1 1 choi criteria response correlated survival results patients achieved objective response according choi longer os non responders median os 19 9 months 95 ci 1 1 38 7 months vs 7 5 months stable disease uncountable ci 3 months progressive disease 95 ci 0 6 2 months log rank test p 0 003 whereas significant survival difference according recist response p 0 339 among 39 recist non responding patients identified responders choi n 31 significantly better os choi non responders median os 19 9 months 95 ci 5 1 34 7 months 5 4 months 95 ci 0 11 6 months p 0 005 conclusions choi criteria appear appropriate recist identify responders long survival among patients received sirt icc pubmed","probabilities":0.9799733,"Title":"Comparison of Choi criteria and Response Evaluation Criteria in Solid Tumors (RECIST) for intrahepatic cholangiocarcinoma treated with glass-microspheres Yttrium-90 selective internal radiation therapy (SIRT)","Abstract":"OBJECTIVE: To compare Choi criteria with Response Evaluation Criteria in Solid Tumors (RECIST) for the prediction of overall survival (OS) in patients treated with glass-microspheres, Yttrium-90 selective internal radiation therapy (SIRT) for intrahepatic cholangiocarcinoma (ICC). METHODS: Between 2010 and 2014, 45 adult patients with locally advanced ICC treated with SIRT were retrospectively analyzed. Computed tomography scans performed before and after treatment were analyzed using both RECIST 1.1 and Choi criteria. Response was correlated with survival. RESULTS: Patients who achieved an objective response according to Choi had a longer OS than non-responders (median OS 19.9 months [95% CI, 1.1-38.7 months] vs. 7.5 months if stable disease [uncountable CI] and 3 months if progressive disease [95% CI, 0-6.2 months], log-rank test: p=0.003) whereas there was no significant survival difference according to the RECIST response (p=0.339). Among the 39 RECIST non-responding patients, those identified as responders by Choi (n=31) had significantly better OS than Choi non-responders (median OS 19.9 months (95% CI, 5.1-34.7 months) and 5.4 months (95% CI, 0-11.6 months), p=0.005). CONCLUSIONS: Choi criteria appear more appropriate than RECIST to identify responders with long survival among patients who received SIRT for ICC.","Source":"PubMed","category":"HUMAN","training_data":"Comparison of Choi criteria and Response Evaluation Criteria in Solid Tumors (RECIST) for intrahepatic cholangiocarcinoma treated with glass-microspheres Yttrium-90 selective internal radiation therapy (SIRT) OBJECTIVE: To compare Choi criteria with Response Evaluation Criteria in Solid Tumors (RECIST) for the prediction of overall survival (OS) in patients treated with glass-microspheres, Yttrium-90 selective internal radiation therapy (SIRT) for intrahepatic cholangiocarcinoma (ICC). METHODS: Between 2010 and 2014, 45 adult patients with locally advanced ICC treated with SIRT were retrospectively analyzed. Computed tomography scans performed before and after treatment were analyzed using both RECIST 1.1 and Choi criteria. Response was correlated with survival. RESULTS: Patients who achieved an objective response according to Choi had a longer OS than non-responders (median OS 19.9 months [95% CI, 1.1-38.7 months] vs. 7.5 months if stable disease [uncountable CI] and 3 months if progressive disease [95% CI, 0-6.2 months], log-rank test: p=0.003) whereas there was no significant survival difference according to the RECIST response (p=0.339). Among the 39 RECIST non-responding patients, those identified as responders by Choi (n=31) had significantly better OS than Choi non-responders (median OS 19.9 months (95% CI, 5.1-34.7 months) and 5.4 months (95% CI, 0-11.6 months), p=0.005). CONCLUSIONS: Choi criteria appear more appropriate than RECIST to identify responders with long survival among patients who received SIRT for ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma among workers printing industry using nocca database elucidate generalisability cluster report japan objectives cluster 11 cases cholangiocarcinoma cc observed small japanese printing firm elucidate whether identified cluster indicative elevated risk cc among workers printing industry large explored risk cancer liver cc among individuals employed printing industry large cohort set four nordic countries finland iceland norway sweden period 45 years methods cohort set linking occupational information censuses national cancer registry data utilising personal identity codes use nordic countries calculated standardised incidence ratios sirs men women working printing industry stratified occupational category typographers printers lithographers bookbinders results among men observed elevated sirs cancer liver 1 35 95 ci 1 14 1 60 142 cases specifically intrahepatic cc 2 34 95 ci 1 45 3 57 21 cases sirs liver cancer especially elevated among printers lithographers sirs intrahepatic cc among typographers printers sirs extrahepatic cc elevated sirs women followed similar pattern number cases low conclusions study supports notion finding excess cc risk among workers small japanese printing firm possibly extends beyond specific firm country studies focus specific exposures occur printing industry pubmed","probabilities":0.9799733,"Title":"Cholangiocarcinoma among workers in the printing industry: using the NOCCA database to elucidate the generalisability of a cluster report from Japan","Abstract":"OBJECTIVES: A cluster of 11 cases of cholangiocarcinoma (CC) was observed in a small Japanese printing firm. To elucidate whether the identified cluster is indicative of an elevated risk of CC among workers in the printing industry at large, we explored the risk of cancer of the liver and CC among individuals employed in the printing industry in a large cohort set-up in four Nordic countries (Finland, Iceland, Norway and Sweden) over a period of 45 years. METHODS: The cohort was set-up by linking occupational information from censuses to national cancer registry data utilising personal identity codes in use in all Nordic countries. We calculated standardised incidence ratios (SIRs) for men and women working in the printing industry, and stratified by occupational category (typographers, printers, lithographers, bookbinders). RESULTS: Among men, we observed elevated SIRs for cancer of the liver (1.35, 95% CI 1.14 to 1.60; 142 cases), specifically intrahepatic CC (2.34, 95% CI 1.45 to 3.57; 21 cases). SIRs for liver cancer were especially elevated among printers and lithographers, and SIRs for intrahepatic CC among typographers and printers. SIRs for extrahepatic CC were not elevated. SIRs for women followed a similar pattern but the number of cases was low. CONCLUSIONS: Our study supports the notion that the finding of excess CC risk among workers in a small Japanese printing firm possibly extends beyond this specific firm and country. Further studies should focus on the specific exposures that occur in the printing industry.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma among workers in the printing industry: using the NOCCA database to elucidate the generalisability of a cluster report from Japan OBJECTIVES: A cluster of 11 cases of cholangiocarcinoma (CC) was observed in a small Japanese printing firm. To elucidate whether the identified cluster is indicative of an elevated risk of CC among workers in the printing industry at large, we explored the risk of cancer of the liver and CC among individuals employed in the printing industry in a large cohort set-up in four Nordic countries (Finland, Iceland, Norway and Sweden) over a period of 45 years. METHODS: The cohort was set-up by linking occupational information from censuses to national cancer registry data utilising personal identity codes in use in all Nordic countries. We calculated standardised incidence ratios (SIRs) for men and women working in the printing industry, and stratified by occupational category (typographers, printers, lithographers, bookbinders). RESULTS: Among men, we observed elevated SIRs for cancer of the liver (1.35, 95% CI 1.14 to 1.60; 142 cases), specifically intrahepatic CC (2.34, 95% CI 1.45 to 3.57; 21 cases). SIRs for liver cancer were especially elevated among printers and lithographers, and SIRs for intrahepatic CC among typographers and printers. SIRs for extrahepatic CC were not elevated. SIRs for women followed a similar pattern but the number of cases was low. CONCLUSIONS: Our study supports the notion that the finding of excess CC risk among workers in a small Japanese printing firm possibly extends beyond this specific firm and country. Further studies should focus on the specific exposures that occur in the printing industry. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer review rare orphan gastrointestinal cancer focus populations new mexico gallbladder cancer rare malignancy biliary tract poor prognosis frequently presenting advanced stage rare united states overall gallbladder cancer elevated incidence geographically distinct locations globe including chile north india korea japan state new mexico united states people native american ancestry much elevated incidence gallbladder cancer compared hispanic non hispanic white populations new mexico gallbladder cancer also one bi gendered cancers elevated female incidence compared men similar gastrointestinal cancers gallbladder cancer etiology likely multi factorial involving combination genomic immunological environmental factors understanding interplay unique epidemiological factors crucial improving prevention early detection treatment lethal disease previous studies failed identify distinct genomic mutational profile gallbladder cancers however work identify promising clinically actionable targets form cancer ongoing examples include interest her2 neu signaling pathway recognition chronic inflammation plays crucial role gallbladder cancer pathogenesis review provide comprehensive overview gallbladder cancer epidemiology risk factors pathogenesis treatment specific focus rural native american populations new mexico conclude review discussing future research directions goal improving clinical outcomes patients lethal malignancy pubmed","probabilities":0.9799733,"Title":"Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico","Abstract":"Gallbladder cancer is a rare malignancy of the biliary tract with a poor prognosis, frequently presenting at an advanced stage. While rare in the United States overall, gallbladder cancer has an elevated incidence in geographically distinct locations of the globe including Chile, North India, Korea, Japan and the state of New Mexico in the United States. People with Native American ancestry have a much elevated incidence of gallbladder cancer compared to Hispanic and non-Hispanic white populations of New Mexico. Gallbladder cancer is also one of the few bi-gendered cancers with an elevated female incidence compared to men. Similar to other gastrointestinal cancers, gallbladder cancer etiology is likely multi-factorial involving a combination of genomic, immunological, and environmental factors. Understanding the interplay of these unique epidemiological factors is crucial in improving the prevention, early detection, and treatment of this lethal disease. Previous studies have failed to identify a distinct genomic mutational profile in gallbladder cancers, however, work to identify promising clinically actionable targets is this form of cancer is ongoing. Examples include, interest in the HER2/Neu signaling pathway and the recognition that chronic inflammation plays a crucial role in gallbladder cancer pathogenesis. In this review, we provide a comprehensive overview of gallbladder cancer epidemiology, risk factors, pathogenesis, and treatment with a specific focus on the rural and Native American populations of New Mexico. We conclude this review by discussing future research directions with the goal of improving clinical outcomes for patients of this lethal malignancy.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder cancer: review of a rare orphan gastrointestinal cancer with a focus on populations of New Mexico Gallbladder cancer is a rare malignancy of the biliary tract with a poor prognosis, frequently presenting at an advanced stage. While rare in the United States overall, gallbladder cancer has an elevated incidence in geographically distinct locations of the globe including Chile, North India, Korea, Japan and the state of New Mexico in the United States. People with Native American ancestry have a much elevated incidence of gallbladder cancer compared to Hispanic and non-Hispanic white populations of New Mexico. Gallbladder cancer is also one of the few bi-gendered cancers with an elevated female incidence compared to men. Similar to other gastrointestinal cancers, gallbladder cancer etiology is likely multi-factorial involving a combination of genomic, immunological, and environmental factors. Understanding the interplay of these unique epidemiological factors is crucial in improving the prevention, early detection, and treatment of this lethal disease. Previous studies have failed to identify a distinct genomic mutational profile in gallbladder cancers, however, work to identify promising clinically actionable targets is this form of cancer is ongoing. Examples include, interest in the HER2/Neu signaling pathway and the recognition that chronic inflammation plays a crucial role in gallbladder cancer pathogenesis. In this review, we provide a comprehensive overview of gallbladder cancer epidemiology, risk factors, pathogenesis, and treatment with a specific focus on the rural and Native American populations of New Mexico. We conclude this review by discussing future research directions with the goal of improving clinical outcomes for patients of this lethal malignancy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumour infiltrating inflammatory immune cells patients extrahepatic cholangiocarcinoma background inflammation immune characteristics tumour microenvironment therapeutic significance aim study investigate clinical impact disease progression human extrahepatic cholangiocarcinoma ecc methods total 114 consecutive ecc patients curative resection 2000 2014 enrolled tumour infiltrating cd66b neutrophils tans tumour associated neutrophils cd163 m2 macrophages tams tumour associated macrophages cd8 cells foxp3 regulatory cells tregs assayed immunohistochemistry relationships patient clinicopathological characteristics prognosis evaluated results tumour associated neutrophils inversely correlated cd8 cells p 0 0001 positively correlated tregs p 0 001 high tans p 0 01 low cd8 cells p 0 02 high tregs p 0 04 significantly associated poor overall survival os high risk signature derived integration intratumoural inflammatory immune cells significantly associated poor recurrence free survival p 0 01 os p 0 0008 high risk signature correlated postoperative distant metastases furthermore high risk signature related resistance gemcitabine based chemotherapy used recurrence conclusions data showed tumour infiltrating inflammatory immune cells may play pivotal role ecc progression high risk signature predicted poor prognosis ecc patients pubmed","probabilities":0.8684211,"Title":"Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC). METHODS: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b(+) neutrophils (TANs; tumour associated neutrophils), CD163(+) M2 macrophages (TAMs; tumour associated macrophages), CD8(+) T cells, and FOXP3(+) regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated. RESULTS: Tumour associated neutrophils were inversely correlated with CD8(+) T cells (P=0.0001) and positively correlated with Tregs (P=0.001). High TANs (P=0.01), low CD8(+) T cells (P=0.02), and high Tregs (P=0.04) were significantly associated with poor overall survival (OS). A high-risk signature, derived from integration of intratumoural inflammatory and immune cells, was significantly associated with poor recurrence-free survival (P=0.01) and OS (P=0.0008). A high-risk signature was correlated with postoperative distant metastases. Furthermore, a high-risk signature was related to the resistance to gemcitabine-based chemotherapy used after recurrence. CONCLUSIONS: Our data showed that tumour infiltrating inflammatory and immune cells may play a pivotal role in ECC progression and a high-risk signature predicted poor prognosis in ECC patients.","Source":"PubMed","category":"HUMAN","training_data":"Tumour-infiltrating inflammatory and immune cells in patients with extrahepatic cholangiocarcinoma BACKGROUND: Inflammation and immune characteristics of the tumour microenvironment have therapeutic significance. The aim of this study was to investigate the clinical impact on disease progression in human extrahepatic cholangiocarcinoma (ECC). METHODS: A total of 114 consecutive ECC patients with curative resection between 2000 and 2014 were enrolled. Tumour infiltrating CD66b(+) neutrophils (TANs; tumour associated neutrophils), CD163(+) M2 macrophages (TAMs; tumour associated macrophages), CD8(+) T cells, and FOXP3(+) regulatory T cells (Tregs) were assayed by immunohistochemistry, and their relationships with patient clinicopathological characteristics and prognosis were evaluated. RESULTS: Tumour associated neutrophils were inversely correlated with CD8(+) T cells (P=0.0001) and positively correlated with Tregs (P=0.001). High TANs (P=0.01), low CD8(+) T cells (P=0.02), and high Tregs (P=0.04) were significantly associated with poor overall survival (OS). A high-risk signature, derived from integration of intratumoural inflammatory and immune cells, was significantly associated with poor recurrence-free survival (P=0.01) and OS (P=0.0008). A high-risk signature was correlated with postoperative distant metastases. Furthermore, a high-risk signature was related to the resistance to gemcitabine-based chemotherapy used after recurrence. CONCLUSIONS: Our data showed that tumour infiltrating inflammatory and immune cells may play a pivotal role in ECC progression and a high-risk signature predicted poor prognosis in ECC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"trends treatment survival gallbladder cancer netherlands identifying gaps opportunities nation wide cohort gallbladder cancer gbc rare western populations data treatment outcomes scarce study aims analyze survival identify opportunities improvement using population based data low incidence country gbc patients diagnosed 2005 2016 gbc identified netherlands cancer registry patients grouped according time period 2005 2009 2010 2016 disease stage trends treatment overall survival os analyzed total 1834 patients included 661 36 patients resected 278 15 non resected non metastatic 895 49 metastatic gbc use radical versus simple cholecystectomy 12 vs 26 p 0 001 early pt1b t2 gbc increased patients metastatic gbc received chemotherapy 11 vs 29 p 0 001 os improved 4 8 months 2005 2009 6 1 months 2010 2016 p 0 012 median os increased time 2005 2009 vs 2010 2016 resected 19 4 26 8 months p 0 038 metastatic 2 3 vs 3 4 months p 0 001 gbc unresected non metastatic gbc early gbc patients radical cholecystectomy median os 76 7 compared 18 4 months simple cholecystectomy p 0 001 palliative chemotherapy showed superior p 0 001 survival metastatic 7 3 versus 2 1 months non resected non metastatic 7 7 versus 3 5 months gbc conclusion survival gbc remains poor radical surgery palliative chemotherapy appear improve prognosis remain utilized google scholar","probabilities":0.9799733,"Title":"Trends In Treatment And Survival Of Gallbladder Cancer In The Netherlands; Identifying Gaps And Opportunities From A Nation-Wide Cohort","Abstract":"Gallbladder cancer (GBC) is rare in Western populations and data about treatment and outcomes are scarce. This study aims to analyze survival and identify opportunities for improvement using population-based data from a low-incidence country. GBC patients diagnosed between 2005 and 2016 with GBC were identified from the Netherlands Cancer Registry. Patients were grouped according to time period (2005–2009/2010–2016) and disease stage. Trends in treatment and overall survival (OS) were analyzed. In total 1834 patients were included: 661 (36%) patients with resected, 278 (15%) with non-resected non-metastatic, and 895 (49%) with metastatic GBC. Use of radical versus simple cholecystectomy (12% vs. 26%, p < 0.001) in early (pT1b/T2) GBC increased. More patients with metastatic GBC received chemotherapy (11% vs. 29%, p < 0.001). OS improved from 4.8 months (2005–2009) to 6.1 months (2010–2016) (p = 0.012). Median OS increased over time (2005–2009 vs. 2010–2016) in resected (19.4 to 26.8 months, p = 0.038) and metastatic (2.3 vs. 3.4 months, p = 0.001) GBC but not in unresected, non-metastatic GBC. In early GBC, patients with radical cholecystectomy had a median OS of 76.7 compared to 18.4 months for simple cholecystectomy (p < 0.001). Palliative chemotherapy showed superior (p < 0.001) survival in metastatic (7.3 versus 2.1 months) and non-resected non-metastatic (7.7 versus 3.5 months) GBC. In conclusion, survival of GBC remains poor. Radical surgery and palliative chemotherapy appear to improve prognosis but remain under-utilized.","Source":"Google Scholar","category":"HUMAN","training_data":"Trends In Treatment And Survival Of Gallbladder Cancer In The Netherlands; Identifying Gaps And Opportunities From A Nation-Wide Cohort Gallbladder cancer (GBC) is rare in Western populations and data about treatment and outcomes are scarce. This study aims to analyze survival and identify opportunities for improvement using population-based data from a low-incidence country. GBC patients diagnosed between 2005 and 2016 with GBC were identified from the Netherlands Cancer Registry. Patients were grouped according to time period (2005–2009/2010–2016) and disease stage. Trends in treatment and overall survival (OS) were analyzed. In total 1834 patients were included: 661 (36%) patients with resected, 278 (15%) with non-resected non-metastatic, and 895 (49%) with metastatic GBC. Use of radical versus simple cholecystectomy (12% vs. 26%, p < 0.001) in early (pT1b/T2) GBC increased. More patients with metastatic GBC received chemotherapy (11% vs. 29%, p < 0.001). OS improved from 4.8 months (2005–2009) to 6.1 months (2010–2016) (p = 0.012). Median OS increased over time (2005–2009 vs. 2010–2016) in resected (19.4 to 26.8 months, p = 0.038) and metastatic (2.3 vs. 3.4 months, p = 0.001) GBC but not in unresected, non-metastatic GBC. In early GBC, patients with radical cholecystectomy had a median OS of 76.7 compared to 18.4 months for simple cholecystectomy (p < 0.001). Palliative chemotherapy showed superior (p < 0.001) survival in metastatic (7.3 versus 2.1 months) and non-resected non-metastatic (7.7 versus 3.5 months) GBC. In conclusion, survival of GBC remains poor. Radical surgery and palliative chemotherapy appear to improve prognosis but remain under-utilized. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"transarterial hepatic yttrium 90 radioembolization patients unresectable intrahepatic cholangiocarcinoma factors associated prolonged survival introduction unresectable intrahepatic cholangiocarcinoma icc systemic chemotherapy often viewed option although efficacy limited radioembolization re using yttrium 90 90 y microspheres accepted therapy patients hepatocellular carcinoma metastatic liver tumors however limited data value re patients icc data factors influencing prognosis purpose retrospective analysis establish factors influenced time progression ttp overall survival os methods patients unresectable icc treated 90 y resin microspheres assessed 3 monthly intervals radiologic response evaluated using response criteria solid tumors recist baseline characteristics biochemical clinical toxicities response examined impact ttp os results thirty four treatments administered 33 patients without major complications recist 12 patients partial response 17 stable disease 5 progressive disease 3 months median os 22 months posttreatment 43 7 months postdiagnosis median ttp 9 8 months survival ttp significantly prolonged patients ecog 0 vs ecog 1 2 median os 29 4 10 5 1 months ttp 17 5 6 9 2 4 months tumor burden 25 os 26 7 vs 6 months ttp 17 5 vs 2 3 months tumor response pr sd vs pd os 35 5 17 7 vs 5 7 months ttp 31 9 9 8 vs 2 5 months respectively p 0 001 conclusions radioembolization effective safe option patients unresectable icc predictors prolonged survival performance status tumor burden recist response pubmed","probabilities":0.9799733,"Title":"Transarterial hepatic yttrium-90 radioembolization in patients with unresectable intrahepatic cholangiocarcinoma: factors associated with prolonged survival","Abstract":"INTRODUCTION: In unresectable intrahepatic cholangiocarcinoma (ICC), systemic chemotherapy often is viewed as the only option, although efficacy is limited. Radioembolization (RE) using yttrium-90 ((90)Y) microspheres is an accepted therapy for patients with hepatocellular-carcinoma or metastatic liver tumors. However, there are limited data on the value of RE in patients with ICC and few data on factors influencing prognosis. The purpose of our retrospective analysis was to establish which factors influenced time-to-progression (TTP) and overall survival (OS). METHODS: Patients with unresectable ICC were treated with (90)Y resin-microspheres and assessed at 3-monthly intervals. Radiologic response was evaluated by using Response Criteria in Solid Tumors (RECIST). Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on TTP and OS. RESULTS: Thirty-four treatments were administered to 33 patients without major complications. By RECIST, 12 patients had a partial response, 17 had stable disease, and 5 had progressive disease after 3 months. The median OS was 22 months posttreatment and 43.7 months postdiagnosis. Median TTP was 9.8 months. Survival and TTP were significantly prolonged in patients with ECOG 0 (vs. ECOG 1 or 2; median OS: 29.4, 10, and 5.1 months; TTP: 17.5, 6.9, and 2.4 months), tumor burden ≤25% (OS: 26.7 vs. 6 months; TTP: 17.5 vs. 2.3 months), or tumor response (PR or SD vs. PD; OS: 35.5, 17.7 vs. 5.7 months; TTP: 31.9, 9.8 vs. 2.5 months), respectively (P < 0.001). CONCLUSIONS: Radioembolization is an effective and safe option for patients with unresectable ICC. Predictors for prolonged survival are performance status, tumor burden, and RECIST response.","Source":"PubMed","category":"HUMAN","training_data":"Transarterial hepatic yttrium-90 radioembolization in patients with unresectable intrahepatic cholangiocarcinoma: factors associated with prolonged survival INTRODUCTION: In unresectable intrahepatic cholangiocarcinoma (ICC), systemic chemotherapy often is viewed as the only option, although efficacy is limited. Radioembolization (RE) using yttrium-90 ((90)Y) microspheres is an accepted therapy for patients with hepatocellular-carcinoma or metastatic liver tumors. However, there are limited data on the value of RE in patients with ICC and few data on factors influencing prognosis. The purpose of our retrospective analysis was to establish which factors influenced time-to-progression (TTP) and overall survival (OS). METHODS: Patients with unresectable ICC were treated with (90)Y resin-microspheres and assessed at 3-monthly intervals. Radiologic response was evaluated by using Response Criteria in Solid Tumors (RECIST). Baseline characteristics, biochemical/clinical toxicities, and response were examined for impact on TTP and OS. RESULTS: Thirty-four treatments were administered to 33 patients without major complications. By RECIST, 12 patients had a partial response, 17 had stable disease, and 5 had progressive disease after 3 months. The median OS was 22 months posttreatment and 43.7 months postdiagnosis. Median TTP was 9.8 months. Survival and TTP were significantly prolonged in patients with ECOG 0 (vs. ECOG 1 or 2; median OS: 29.4, 10, and 5.1 months; TTP: 17.5, 6.9, and 2.4 months), tumor burden ≤25% (OS: 26.7 vs. 6 months; TTP: 17.5 vs. 2.3 months), or tumor response (PR or SD vs. PD; OS: 35.5, 17.7 vs. 5.7 months; TTP: 31.9, 9.8 vs. 2.5 months), respectively (P < 0.001). CONCLUSIONS: Radioembolization is an effective and safe option for patients with unresectable ICC. Predictors for prolonged survival are performance status, tumor burden, and RECIST response. PubMed","prediction_labels":"HUMAN"},{"cleaned":"y shaped bilateral self expandable metallic stent placement malignant hilar biliary obstruction data referral center palliative care background aim malignant hilar strictures clinical challenge current therapeutic approach poor prognosis recent years self expandable metallic stents proven effective plastic stents palliation malignant hilar strictures bilateral stent stent technique registering high success rate report experience y shaped endoscopic self expandable metallic stents placement treatment advanced malignant hilar strictures methods april 2009 august 2012 prospectively collected data patients treated y shaped sems placement advanced malignant hilar carcinoma data technical success clinical success complications collected results twenty patients 9 males treated mean age 64 2 15 3 years grade malignant hilar strictures according bismuth classification ii 5 patients 25 iiia 1 5 iv 14 70 mean bilirubin level 14 7 4 9 mg dl technical success achieved patients significant reduction bilirubin levels 2 9 1 7 mg dl one patient experienced cholangitis early complication 2 patients stent ingrowth observed stents migration recorded procedure related mortality end follow 7 1 3 1 months 13 20 patients 65 died conclusions experience confirms endoscopic bilateral self expandable metallic stents placement stent stent technique y shaped configuration feasible effective safe procedure palliation unresectable malignant hilar strictures pubmed","probabilities":0.9799733,"Title":"Y-shaped bilateral self-expandable metallic stent placement for malignant hilar biliary obstruction: data from a referral center for palliative care","Abstract":"BACKGROUND AND AIM: Malignant hilar strictures are a clinical challenge because of the current therapeutic approach and the poor prognosis. In recent years, self-expandable metallic stents have proven more effective than plastic stents for palliation of malignant hilar strictures, with the bilateral stent-in-stent technique registering a high success rate. We report our experience with Y-shaped endoscopic self-expandable metallic stents placement for treatment of advanced malignant hilar strictures. METHODS: From April 2009 to August 2012, we prospectively collected data on patients treated with Y-shaped SEMS placement for advanced malignant hilar carcinoma. Data on technical success, clinical success, and complications were collected. RESULTS: Twenty patients (9 males) were treated (mean age 64.2 ± 15.3 years). The grade of malignant hilar strictures according to the Bismuth classification was II in 5 patients (25%), IIIa in 1 (5%), and IV in 14 (70%). The mean bilirubin level was 14.7 ± 4.9 mg/dL. Technical success was achieved in all patients, with a significant reduction in bilirubin levels (2.9 ± 1.7 mg/dL). One patient experienced cholangitis as early complication, while in 2 patients stent ingrowth was observed. No stents migration was recorded. There was no procedure-related mortality. At the end of the follow-up (7.1 ± 3.1 months), 13 of the 20 patients (65%) had died. CONCLUSIONS: Our experience confirms endoscopic bilateral self-expandable metallic stents placement with stent-in-stent technique (Y-shaped configuration) as a feasible, effective, and safe procedure for palliation of unresectable malignant hilar strictures.","Source":"PubMed","category":"HUMAN","training_data":"Y-shaped bilateral self-expandable metallic stent placement for malignant hilar biliary obstruction: data from a referral center for palliative care BACKGROUND AND AIM: Malignant hilar strictures are a clinical challenge because of the current therapeutic approach and the poor prognosis. In recent years, self-expandable metallic stents have proven more effective than plastic stents for palliation of malignant hilar strictures, with the bilateral stent-in-stent technique registering a high success rate. We report our experience with Y-shaped endoscopic self-expandable metallic stents placement for treatment of advanced malignant hilar strictures. METHODS: From April 2009 to August 2012, we prospectively collected data on patients treated with Y-shaped SEMS placement for advanced malignant hilar carcinoma. Data on technical success, clinical success, and complications were collected. RESULTS: Twenty patients (9 males) were treated (mean age 64.2 ± 15.3 years). The grade of malignant hilar strictures according to the Bismuth classification was II in 5 patients (25%), IIIa in 1 (5%), and IV in 14 (70%). The mean bilirubin level was 14.7 ± 4.9 mg/dL. Technical success was achieved in all patients, with a significant reduction in bilirubin levels (2.9 ± 1.7 mg/dL). One patient experienced cholangitis as early complication, while in 2 patients stent ingrowth was observed. No stents migration was recorded. There was no procedure-related mortality. At the end of the follow-up (7.1 ± 3.1 months), 13 of the 20 patients (65%) had died. CONCLUSIONS: Our experience confirms endoscopic bilateral self-expandable metallic stents placement with stent-in-stent technique (Y-shaped configuration) as a feasible, effective, and safe procedure for palliation of unresectable malignant hilar strictures. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gallbladder carcinoma analysis prognostic factors 132 cases objective evaluate prognostic factors gallbladder carcinoma methods presentation operative data complications survival outcome examined 132 gallbladder carcinoma patients underwent gallbladder surgery unit 2002 2007 follow results obtained every patient univariate multivariate survival analysis results univariate analysis showed gallbladder lesion history tumor cell differentiation nevin staging preoperative lymph node metastasis surgical approach significantly correlated prognosis patients p 0 05 results multivariate analysis cox regression showed gallbladder lesion history nevin staging surgical approach independent predicators relative risks 6 9 4 4 2 8 respectively p 0 002 0 003 0 008 conclusion gallbladder lesion history nevin staging surgical approach independent prognostic factors gallbladder carcinoma rapidly fatal disease therefore early diagnosis anti infective therapy radical surgery greatly needed improve prognosis gallbladder carcinoma stn","probabilities":0.54545456,"Title":"Gallbladder Carcinoma: Analysis Of Prognostic Factors In 132 Cases","Abstract":"Objective: To evaluate the prognostic factors of gallbladder carcinoma. \r\n\r\n Methods: Presentation, operative data, complications, and survival outcome were examined for 132 gallbladder carcinoma patients who underwent gallbladder surgery in our unit during 2002-2007, and follow-up results were obtained from every patient for univariate and multivariate survival analysis. \r\n\r\n Results: The univariate analysis showed that gallbladder lesion history, tumor cell differentiation, Nevin staging, preoperative lymph node metastasis and the surgical approach significantly correlated with the prognosis of the patients (p <0.05). The results of the multivariate analysis (Cox regression) showed that gallbladder lesion history, Nevin staging and the surgical approach were independent predicators with relative risks of 6.9, 4.4, 2.8, respectively (p=0.002, 0.003, 0.008). \r\n\r\n Conclusion: Gallbladder lesion history, Nevin staging and the surgical approach are independent prognostic factors for gallbladder carcinoma, a rapidly fatal disease. Therefore, early diagnosis, anti-infective therapy and radical surgery are greatly needed to improve the prognosis of gallbladder carcinoma.","Source":"STN","category":"HUMAN","training_data":"Gallbladder Carcinoma: Analysis Of Prognostic Factors In 132 Cases Objective: To evaluate the prognostic factors of gallbladder carcinoma. \r\n\r\n Methods: Presentation, operative data, complications, and survival outcome were examined for 132 gallbladder carcinoma patients who underwent gallbladder surgery in our unit during 2002-2007, and follow-up results were obtained from every patient for univariate and multivariate survival analysis. \r\n\r\n Results: The univariate analysis showed that gallbladder lesion history, tumor cell differentiation, Nevin staging, preoperative lymph node metastasis and the surgical approach significantly correlated with the prognosis of the patients (p <0.05). The results of the multivariate analysis (Cox regression) showed that gallbladder lesion history, Nevin staging and the surgical approach were independent predicators with relative risks of 6.9, 4.4, 2.8, respectively (p=0.002, 0.003, 0.008). \r\n\r\n Conclusion: Gallbladder lesion history, Nevin staging and the surgical approach are independent prognostic factors for gallbladder carcinoma, a rapidly fatal disease. Therefore, early diagnosis, anti-infective therapy and radical surgery are greatly needed to improve the prognosis of gallbladder carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"medical conditions family history cancer risk biliary tract cancers background scanty data exist role personal medical conditions except gallstones family history cancer risk biliary tract cancers btc methods analyzed issue using data two italian case control studies including 159 cases btc 795 matched hospital controls odds ratios ors btc corresponding 95 confidence intervals cis estimated using multiple logistic regression models results gallstones associated 2 fold excess risk btc 95 ci 1 24 3 45 significant associations observed conditions investigated including diabetes 1 15 95 ci 0 63 2 11 hypertension 0 65 95 ci 0 39 1 11 hyperlipidemia 0 61 95 ci 0 31 1 21 allergy 0 64 95 ci 0 29 1 40 gastroduodenal ulcer 0 52 95 ci 0 24 1 12 hepatitis 2 02 95 ci 0 35 11 67 benign thyroid diseases 1 16 95 ci 0 56 2 40 hysterectomy 1 19 95 ci 0 53 2 68 unilateral oophorectomy 1 75 95 ci 0 44 6 93 bilateral oophorectomy 2 48 95 ci 0 79 7 82 found excess risk btc relation family history cancer 1 52 95 ci 1 03 2 24 family history gallbladder cancer 3 83 95 ci 0 59 24 75 conclusions present study confirms strong association btc history gallstones provides evidence positive association family history cancer pubmed","probabilities":0.9799733,"Title":"Medical conditions, family history of cancer, and the risk of biliary tract cancers","Abstract":"BACKGROUND: Scanty data exist on the role of personal medical conditions, except for gallstones, and family history of cancer on the risk of biliary tract cancers (BTC). METHODS: We analyzed this issue using data from two Italian case-control studies, including 159 cases of BTC and 795 matched hospital controls. Odds ratios (ORs) of BTC and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression models. RESULTS: Gallstones were associated with a 2-fold excess risk of BTC (95% CI 1.24-3.45). No significant associations were observed with other conditions investigated, including diabetes (OR 1.15, 95% CI 0.63-2.11), hypertension (OR 0.65, 95% CI 0.39-1.11), hyperlipidemia (OR 0.61, 95% CI 0.31-1.21), allergy (OR 0.64, 95% CI 0.29-1.40), gastroduodenal ulcer (OR 0.52, 95% CI 0.24-1.12), hepatitis (OR 2.02, 95% CI 0.35-11.67), benign thyroid diseases (OR 1.16, 95% CI 0.56-2.40), hysterectomy (OR 1.19, 95% CI 0.53-2.68), unilateral oophorectomy (OR 1.75, 95% CI 0.44-6.93), and bilateral oophorectomy (OR 2.48, 95% CI 0.79-7.82). We found an excess risk of BTC in relation to family history of any cancer (OR 1.52, 95% CI 1.03-2.24) and family history of gallbladder cancer (OR 3.83, 95% CI 0.59-24.75). CONCLUSIONS: The present study confirms a strong association between BTC and history of gallstones, and provides further evidence of a positive association with family history of cancer.","Source":"PubMed","category":"HUMAN","training_data":"Medical conditions, family history of cancer, and the risk of biliary tract cancers BACKGROUND: Scanty data exist on the role of personal medical conditions, except for gallstones, and family history of cancer on the risk of biliary tract cancers (BTC). METHODS: We analyzed this issue using data from two Italian case-control studies, including 159 cases of BTC and 795 matched hospital controls. Odds ratios (ORs) of BTC and corresponding 95% confidence intervals (CIs) were estimated using multiple logistic regression models. RESULTS: Gallstones were associated with a 2-fold excess risk of BTC (95% CI 1.24-3.45). No significant associations were observed with other conditions investigated, including diabetes (OR 1.15, 95% CI 0.63-2.11), hypertension (OR 0.65, 95% CI 0.39-1.11), hyperlipidemia (OR 0.61, 95% CI 0.31-1.21), allergy (OR 0.64, 95% CI 0.29-1.40), gastroduodenal ulcer (OR 0.52, 95% CI 0.24-1.12), hepatitis (OR 2.02, 95% CI 0.35-11.67), benign thyroid diseases (OR 1.16, 95% CI 0.56-2.40), hysterectomy (OR 1.19, 95% CI 0.53-2.68), unilateral oophorectomy (OR 1.75, 95% CI 0.44-6.93), and bilateral oophorectomy (OR 2.48, 95% CI 0.79-7.82). We found an excess risk of BTC in relation to family history of any cancer (OR 1.52, 95% CI 1.03-2.24) and family history of gallbladder cancer (OR 3.83, 95% CI 0.59-24.75). CONCLUSIONS: The present study confirms a strong association between BTC and history of gallstones, and provides further evidence of a positive association with family history of cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"k ras mutation strongly associated perineural invasion represents independent prognostic factor intrahepatic cholangiocarcinoma hepatectomy background unsatisfying long term survival intrahepatic cholangiocarcinoma icc triggers clinicians searching molecular markers k ras mutation tailor management strategy additionally emergence tyrosine kinase inhibitors tkis brings new hope palliate advanced icc whether efficacy tkis influenced k ras mutation largely unknown study designed determine prevalence k ras mutation clinical significance icc well pave reference future application tkis methods total 86 patients icc underwent hepatectomy retrospectively recruited k ras mutation determined using laser capture microdissection direct sequencing method association among clinicopathological variables k ras mutation analyzed prognostic factors icc hepatectomy also determined results nineteen 22 patients exhibited k ras mutations seventeen k ras mutations occurring codon 12 remaining two occurring codon 13 codon 61 one perineural invasion exclusively variable associated k ras mutation odds ratio 6 9 using logistic regression analysis multivariate analysis demonstrated resection margin status nodal metastasis k ras mutation independent prognostic factors median survival icc patients k ras mutation 5 7 months compared 19 0 months without k ras mutation p 0 002 conclusions prevalence k ras mutations considerably large cohort icc 22 k ras mutation strongly associated perineural invasion phenotypically k ras mutation independent prognostic factor icc hepatectomy pubmed","probabilities":0.9799733,"Title":"K-ras mutation is strongly associated with perineural invasion and represents an independent prognostic factor of intrahepatic cholangiocarcinoma after hepatectomy","Abstract":"BACKGROUND: Unsatisfying long-term survival of intrahepatic cholangiocarcinoma (ICC) triggers the clinicians searching for molecular markers, such as K-ras mutation, to tailor management strategy. Additionally, emergence of tyrosine kinase inhibitors (TKIs) brings new hope to palliate advanced ICC; whether the efficacy of TKIs is influenced by k-ras mutation is largely unknown. This study was designed to determine the prevalence of k-ras mutation and its clinical significance in ICC, as well as to pave the reference for future application of TKIs. METHODS: A total of 86 patients with ICC who underwent hepatectomy were retrospectively recruited. K-ras mutation was determined by using laser capture microdissection and direct sequencing method. Association among clinicopathological variables and K-ras mutation was analyzed. Prognostic factors of ICC after hepatectomy also were determined. RESULTS: Nineteen (22%) patients exhibited K-ras mutations. Seventeen had their K-ras mutations occurring at codon 12, and the remaining two occurring at codon 13 and codon 61 in one each. Perineural invasion was exclusively the variable associated with K-ras mutation (odds ratio, 6.9) using logistic regression analysis. Multivariate analysis demonstrated that resection margin, T-status, nodal metastasis, and K-ras mutation were independent prognostic factors. The median survival of ICC patients with K-ras mutation was 5.7 months compared with 19.0 months in those without K-ras mutation (P = 0.002). CONCLUSIONS: The prevalence of K-ras mutations in a considerably large cohort of ICC was 22%. K-ras mutation is strongly associated with perineural invasion phenotypically. K-ras mutation is an independent prognostic factor of ICC after hepatectomy.","Source":"PubMed","category":"HUMAN","training_data":"K-ras mutation is strongly associated with perineural invasion and represents an independent prognostic factor of intrahepatic cholangiocarcinoma after hepatectomy BACKGROUND: Unsatisfying long-term survival of intrahepatic cholangiocarcinoma (ICC) triggers the clinicians searching for molecular markers, such as K-ras mutation, to tailor management strategy. Additionally, emergence of tyrosine kinase inhibitors (TKIs) brings new hope to palliate advanced ICC; whether the efficacy of TKIs is influenced by k-ras mutation is largely unknown. This study was designed to determine the prevalence of k-ras mutation and its clinical significance in ICC, as well as to pave the reference for future application of TKIs. METHODS: A total of 86 patients with ICC who underwent hepatectomy were retrospectively recruited. K-ras mutation was determined by using laser capture microdissection and direct sequencing method. Association among clinicopathological variables and K-ras mutation was analyzed. Prognostic factors of ICC after hepatectomy also were determined. RESULTS: Nineteen (22%) patients exhibited K-ras mutations. Seventeen had their K-ras mutations occurring at codon 12, and the remaining two occurring at codon 13 and codon 61 in one each. Perineural invasion was exclusively the variable associated with K-ras mutation (odds ratio, 6.9) using logistic regression analysis. Multivariate analysis demonstrated that resection margin, T-status, nodal metastasis, and K-ras mutation were independent prognostic factors. The median survival of ICC patients with K-ras mutation was 5.7 months compared with 19.0 months in those without K-ras mutation (P = 0.002). CONCLUSIONS: The prevalence of K-ras mutations in a considerably large cohort of ICC was 22%. K-ras mutation is strongly associated with perineural invasion phenotypically. K-ras mutation is an independent prognostic factor of ICC after hepatectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic relevance number ratio metastatic lymph nodes resected pancreatic ampullary distal bile duct carcinomas background lymph node ratio lnr may useful nodal n status prognostic subclassification adenocarcinomas pancreatoduodenectomy ampullary ac biliary dbc pancreatic pc adenocarcinomas biologically distinct nodal involvement may different prognostic importance among separate cancers methods included 179 consecutive pancreatoduodenectomies pc ac dbc performed standardized histopathologic evaluation including prospective registration retrospective reevaluation cancer origin associations histopathologic variables lnr n status number metastatic nodes evaluated unadjusted adjusted survival analysis performed results overall 5 year survival 6 pc n 72 26 dbc n 46 46 ac n 61 lymph node involvement frequent pc 75 ac 48 dbc 57 pc n status discriminate prognostic groups n1 vs n0 p 0 31 however increasing lnr associated poorer survival unadjusted analysis well adjusting margin involvement degree differentiation tumor diameter p 0 032 hazard ratio 1 87 95 confidence interval 1 06 3 31 ac dbc n status clearly discriminated subgroups patients different long term survival unadjusted adjusted survival analysis n1 vs n0 p 0 001 whereas number metastatic nodes lnr predict survival among node positive resections conclusions predictive value nodal involvement depends type cancer within pancreatic head ac dbc n status adequately discriminates good poor prognosis pc lnr may powerful prognostic subclassification pubmed","probabilities":0.9799733,"Title":"Prognostic relevance of number and ratio of metastatic lymph nodes in resected pancreatic, ampullary, and distal bile duct carcinomas","Abstract":"BACKGROUND: Lymph node ratio (LNR) may be more useful than nodal (N) status in prognostic subclassification of adenocarcinomas after pancreatoduodenectomy. Ampullary (AC), biliary (DBC), and pancreatic (PC) adenocarcinomas are biologically distinct, and nodal involvement may have different prognostic importance among these separate cancers. METHODS: We included 179 consecutive pancreatoduodenectomies for PC, AC, or DBC, and performed standardized histopathologic evaluation, including prospective registration and retrospective reevaluation of the cancer origin. Associations between histopathologic variables and LNR, N status, and number of metastatic nodes were evaluated. Unadjusted and adjusted survival analysis was performed. RESULTS: Overall 5 year survival was 6% for PC (n=72), 26% for DBC (n=46), and 46% for AC (n=61). Lymph node involvement was more frequent in PC (75%) than in AC (48%) and DBC (57%). In PC, N status did not discriminate between prognostic groups (N1 vs. N0; p=0.31). However, increasing LNR was associated with poorer survival in unadjusted analysis, as well as when adjusting for margin involvement, degree of differentiation, and tumor diameter (p=0.032; hazard ratio 1.87, 95% confidence interval 1.06-3.31). In AC and DBC, N status clearly discriminated between subgroups of patients with different long-term survival in unadjusted and adjusted survival analysis (N1 vs. N0; p<0.001), whereas number of metastatic nodes and LNR did not predict survival among node-positive resections. CONCLUSIONS: The predictive value of nodal involvement depends on the type of cancer within the pancreatic head. In AC and DBC, N status adequately discriminates between good and poor prognosis. In PC, LNR may be more powerful in prognostic subclassification.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic relevance of number and ratio of metastatic lymph nodes in resected pancreatic, ampullary, and distal bile duct carcinomas BACKGROUND: Lymph node ratio (LNR) may be more useful than nodal (N) status in prognostic subclassification of adenocarcinomas after pancreatoduodenectomy. Ampullary (AC), biliary (DBC), and pancreatic (PC) adenocarcinomas are biologically distinct, and nodal involvement may have different prognostic importance among these separate cancers. METHODS: We included 179 consecutive pancreatoduodenectomies for PC, AC, or DBC, and performed standardized histopathologic evaluation, including prospective registration and retrospective reevaluation of the cancer origin. Associations between histopathologic variables and LNR, N status, and number of metastatic nodes were evaluated. Unadjusted and adjusted survival analysis was performed. RESULTS: Overall 5 year survival was 6% for PC (n=72), 26% for DBC (n=46), and 46% for AC (n=61). Lymph node involvement was more frequent in PC (75%) than in AC (48%) and DBC (57%). In PC, N status did not discriminate between prognostic groups (N1 vs. N0; p=0.31). However, increasing LNR was associated with poorer survival in unadjusted analysis, as well as when adjusting for margin involvement, degree of differentiation, and tumor diameter (p=0.032; hazard ratio 1.87, 95% confidence interval 1.06-3.31). In AC and DBC, N status clearly discriminated between subgroups of patients with different long-term survival in unadjusted and adjusted survival analysis (N1 vs. N0; p<0.001), whereas number of metastatic nodes and LNR did not predict survival among node-positive resections. CONCLUSIONS: The predictive value of nodal involvement depends on the type of cancer within the pancreatic head. In AC and DBC, N status adequately discriminates between good and poor prognosis. In PC, LNR may be more powerful in prognostic subclassification. PubMed","prediction_labels":"HUMAN"},{"cleaned":"elevated pre operative neutrophil lymphocyte ratio predicts disease free survival following pancreatic resection periampullary carcinomas background pre operative neutrophil lymphocyte ratio nlr 5 associated reduced survival patients various gastrointestinal tract cancers however prognostic value patients periampullary tumour reported date objectives determine prognostic value pre operative nlr terms survival recurrence resected periampullary carcinomas methods retrospective cohort study consecutive patients undergoing pancreatoduodenectomy pd periampullary carcinoma pancreatic ampullary cholangiocarcinoma identified departmental database effect nlr upon survival recurrence explored results overall median survival amongst 228 patients 24 months inter quartile range iqr 12 43 median survival whose nlr 5 significantly greater patients whose nlr 5 24 months iqr 14 42 versus 13 months iqr 8 48 respectively p 0 234 however developed recurrence survival greater nlr 5 20 months iqr 12 27 versus 11 months iqr 7 22 respectively p 0 038 effect marked patients cholangiocarcinoma p 0 019 whilst trend worse survival seen pancreatic adenocarcinoma effect seen patients ampullary carcinoma p 0 516 conclusions study provides evidence pre operative nlr offers important prognostic information regarding disease free survival effect however dependent upon tumour type amongst patients undergoing pd pubmed","probabilities":0.9799733,"Title":"Elevated pre-operative neutrophil to lymphocyte ratio predicts disease free survival following pancreatic resection for periampullary carcinomas","Abstract":"BACKGROUND: The pre-operative neutrophil-to-lymphocyte ratio (NLR), when ≥5 has been associated with reduced survival for patients with various gastrointestinal tract cancers, however, it's prognostic value in patients with periampullary tumour has not been reported to date. OBJECTIVES: To determine the prognostic value of pre-operative NLR in terms of survival and recurrence of resected periampullary carcinomas. METHODS: This was a retrospective cohort study of consecutive patients undergoing pancreatoduodenectomy (PD) for periampullary carcinoma (pancreatic, ampullary, cholangiocarcinoma) identified from a departmental database. The effect of NLR upon survival and recurrence was explored. RESULTS: Overall median survival amongst 228 patients was 24 months (inter-quartile range [IQR]: 12-43). The median survival for those whose NLR was <5 was not significantly greater than those patients whose NLR was ≥5 (24 months [IQR: 14-42] versus 13 months [IQR: 8-48], respectively; p = 0.234). However, for those that developed recurrence, survival was greater in those with an NLR <5 at (20 months [IQR: 12-27] versus 11 months [IQR: 7-22], respectively; p = 0.038). This effect was most marked in those patients with cholangiocarcinoma (p = 0.019) whilst a trend to worse survival was seen in those with pancreatic adenocarcinoma. No effect was seen in patients with ampullary carcinoma (p = 0.516). CONCLUSIONS: This study provides further evidence that pre-operative NLR offers important prognostic information regarding disease-free survival. This effect, however, is dependent upon the tumour type amongst patients undergoing PD.","Source":"PubMed","category":"HUMAN","training_data":"Elevated pre-operative neutrophil to lymphocyte ratio predicts disease free survival following pancreatic resection for periampullary carcinomas BACKGROUND: The pre-operative neutrophil-to-lymphocyte ratio (NLR), when ≥5 has been associated with reduced survival for patients with various gastrointestinal tract cancers, however, it's prognostic value in patients with periampullary tumour has not been reported to date. OBJECTIVES: To determine the prognostic value of pre-operative NLR in terms of survival and recurrence of resected periampullary carcinomas. METHODS: This was a retrospective cohort study of consecutive patients undergoing pancreatoduodenectomy (PD) for periampullary carcinoma (pancreatic, ampullary, cholangiocarcinoma) identified from a departmental database. The effect of NLR upon survival and recurrence was explored. RESULTS: Overall median survival amongst 228 patients was 24 months (inter-quartile range [IQR]: 12-43). The median survival for those whose NLR was <5 was not significantly greater than those patients whose NLR was ≥5 (24 months [IQR: 14-42] versus 13 months [IQR: 8-48], respectively; p = 0.234). However, for those that developed recurrence, survival was greater in those with an NLR <5 at (20 months [IQR: 12-27] versus 11 months [IQR: 7-22], respectively; p = 0.038). This effect was most marked in those patients with cholangiocarcinoma (p = 0.019) whilst a trend to worse survival was seen in those with pancreatic adenocarcinoma. No effect was seen in patients with ampullary carcinoma (p = 0.516). CONCLUSIONS: This study provides further evidence that pre-operative NLR offers important prognostic information regarding disease-free survival. This effect, however, is dependent upon the tumour type amongst patients undergoing PD. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value preoperative inflammatory indexes gallbladder carcinoma hepatic involvement background neutrophil lymphocyte ratio nlr platelet lymphocyte ratio plr considered indicators prognosis various cancers however prognostic values nlr plr never tested gallbladder carcinoma gbc hepatic involvement objective aim current study assess prognostic significance nlr plr candidate biomarkers gbc liver involvement methods receiver operating characteristic roc curve analyses utilized pinpoint cut values nlr plr monocyte lymphocyte ratio mlr univariate analyses employed estimate impact nlr plr mlr inflammatory indexes median survival multivariate analyses used verify independent prognostic predictors results eighty four patients enrolled 2009 2017 cut values nlr plr mlr 3 20 117 75 0 25 respectively univariate analyses revealed tnm stage nlr plr mlr lactate dehydrogenase alkaline phosphatase carcinoembryonic antigen significantly associated decreased survival gbc hepatic involvement advanced tnm stage p 0 001 elevated preoperative nlr p 0 002 significantly associated lower median survival periods revealed multivariate analyses conclusions findings suggest preoperative nlr may independent prognostic factor evaluating prognosis gbc liver involvement pubmed","probabilities":0.9799733,"Title":"The prognostic value of preoperative inflammatory indexes in gallbladder carcinoma with hepatic involvement","Abstract":"BACKGROUND: Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio (PLR) have been considered as indicators for prognosis in various cancers. However, the prognostic values of NLR and PLR have never been tested in gallbladder carcinoma (GBC) with hepatic involvement. OBJECTIVE: The aim of the current study was to assess the prognostic significance of NLR, PLR, and other candidate biomarkers in GBC with liver involvement. METHODS: Receiver operating characteristic (ROC) curve analyses were utilized to pinpoint the cut-off values for NLR, PLR, and Monocyte-Lymphocyte Ratio (MLR). Univariate analyses were employed to estimate the impact of NLR, PLR, MLR, and other inflammatory indexes on median survival. Multivariate analyses were used to verify the independent prognostic predictors. RESULTS: Eighty four patients were enrolled from 2009 to 2017. The cut-off values for NLR, PLR, and MLR were 3.20, 117.75, and 0.25, respectively. Univariate analyses revealed that TNM stage, NLR, PLR, MLR, lactate dehydrogenase, alkaline phosphatase, and carcinoembryonic antigen were significantly associated with decreased survival in GBC with hepatic involvement. Advanced TNM stage (P< 0.001) and elevated preoperative NLR (P= 0.002) were significantly associated with lower median survival periods, as revealed by multivariate analyses. CONCLUSIONS: These findings suggest that preoperative NLR may be an independent prognostic factor in evaluating prognosis in GBC with liver involvement.","Source":"PubMed","category":"HUMAN","training_data":"The prognostic value of preoperative inflammatory indexes in gallbladder carcinoma with hepatic involvement BACKGROUND: Neutrophil-Lymphocyte Ratio (NLR) and Platelet-Lymphocyte Ratio (PLR) have been considered as indicators for prognosis in various cancers. However, the prognostic values of NLR and PLR have never been tested in gallbladder carcinoma (GBC) with hepatic involvement. OBJECTIVE: The aim of the current study was to assess the prognostic significance of NLR, PLR, and other candidate biomarkers in GBC with liver involvement. METHODS: Receiver operating characteristic (ROC) curve analyses were utilized to pinpoint the cut-off values for NLR, PLR, and Monocyte-Lymphocyte Ratio (MLR). Univariate analyses were employed to estimate the impact of NLR, PLR, MLR, and other inflammatory indexes on median survival. Multivariate analyses were used to verify the independent prognostic predictors. RESULTS: Eighty four patients were enrolled from 2009 to 2017. The cut-off values for NLR, PLR, and MLR were 3.20, 117.75, and 0.25, respectively. Univariate analyses revealed that TNM stage, NLR, PLR, MLR, lactate dehydrogenase, alkaline phosphatase, and carcinoembryonic antigen were significantly associated with decreased survival in GBC with hepatic involvement. Advanced TNM stage (P< 0.001) and elevated preoperative NLR (P= 0.002) were significantly associated with lower median survival periods, as revealed by multivariate analyses. CONCLUSIONS: These findings suggest that preoperative NLR may be an independent prognostic factor in evaluating prognosis in GBC with liver involvement. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatitis b virus infection intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc devastating malignant tumor arising peripheral intrahepatic bile duct epithelium incidence mortality icc markedly increasing past two decades worldwide though cause rise incidence unclear thus intensifying search alternative etiological agents pathogenetic mechanisms hepatolithiasis primary sclerosing cholangitis parasitic infection opisthorchis viverrini clonorchis sinensis fibropolycystic liver disease chemical carcinogen exposure thought risk factors icc nevertheless majority icc patients risk factors none established risk factors explain recent increasing trend icc therefore identifying risk factors may lead prevention early detection icc chronic hepatitis b virus hbv infection predominant cause hepatocellular carcinoma hbv endemic areas review discusses evidence implicating chronic hbv infection likely etiology icc pathogenetic mechanisms might involved pubmed","probabilities":0.9799733,"Title":"Hepatitis B virus infection and intrahepatic cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant tumor arising from the peripheral intrahepatic bile duct epithelium. The incidence and mortality of ICC is markedly increasing over the past two decades worldwide, though the cause for this rise in incidence is unclear, thus intensifying the search for alternative etiological agents and pathogenetic mechanisms. Hepatolithiasis, primary sclerosing cholangitis, parasitic infection (Opisthorchis viverrini or Clonorchis sinensis), fibropolycystic liver disease, and chemical carcinogen exposure are thought to be the risk factors for ICC. Nevertheless, the majority of ICC patients do not have any of these risk factors, and none of the established risk factors can explain the recent increasing trend of ICC. Therefore, identifying other risk factors may lead to the prevention and early detection of ICC. Chronic hepatitis B virus (HBV) infection is the predominant cause of hepatocellular carcinoma in HBV-endemic areas. This review discusses the evidence implicating chronic HBV infection as a likely etiology of ICC and the pathogenetic mechanisms that might be involved.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis B virus infection and intrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is a devastating malignant tumor arising from the peripheral intrahepatic bile duct epithelium. The incidence and mortality of ICC is markedly increasing over the past two decades worldwide, though the cause for this rise in incidence is unclear, thus intensifying the search for alternative etiological agents and pathogenetic mechanisms. Hepatolithiasis, primary sclerosing cholangitis, parasitic infection (Opisthorchis viverrini or Clonorchis sinensis), fibropolycystic liver disease, and chemical carcinogen exposure are thought to be the risk factors for ICC. Nevertheless, the majority of ICC patients do not have any of these risk factors, and none of the established risk factors can explain the recent increasing trend of ICC. Therefore, identifying other risk factors may lead to the prevention and early detection of ICC. Chronic hepatitis B virus (HBV) infection is the predominant cause of hepatocellular carcinoma in HBV-endemic areas. This review discusses the evidence implicating chronic HBV infection as a likely etiology of ICC and the pathogenetic mechanisms that might be involved. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors benefits adjuvant therapy pancreatoduodenectomy ampullary adenocarcinoma mayo clinic experience introduction ampullary adenocarcinoma rare entity limited data prognostic factors aim study identify prognostic factors assess benefit adjuvant therapy patients ampullary adenocarcinoma underwent pancreatoduodenectomy methods cohort 121 consecutive patients underwent pancreatoduodenectomy ampullary adenocarcinoma 2006 2016 mayo clinic rochester mn patients confirmed independent pathologic review ampullary carcinoma patient survival correlation patient tumor variables evaluated univariate multivariate analysis results fifty three patients 45 received adjuvant therapy 34 patients chemotherapy alone 19 patients received chemotherapy radiation therapy fifty seven percent patients diagnosed advanced stage disease stage iib higher nearly patients 98 3 negative surgical margins median overall survival os 91 8 months 95 ci 52 6 months reached multivariate analysis excellent performance status ecog 0 adjuvant therapy advanced stage remained statistically significant adjuvant therapy independently associated improved disease free survival hazard ratio hr 0 52 p 0 04 overall survival hr 0 45 p 0 03 patients advanced disease conclusions adjuvant therapy associated improved survival patients resected ampullary cancer especially advanced stage disease multi institutional randomized trial needed assess role adjuvant therapy ampullary adenocarcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience","Abstract":"INTRODUCTION: Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. METHODS: A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. RESULTS: Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. CONCLUSIONS: Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors and benefits of adjuvant therapy after pancreatoduodenectomy for ampullary adenocarcinoma: Mayo Clinic experience INTRODUCTION: Ampullary adenocarcinoma is a rare entity with limited data on prognostic factors. The aim of this study is to identify prognostic factors and assess the benefit of adjuvant therapy in patients with ampullary adenocarcinoma who underwent pancreatoduodenectomy. METHODS: A cohort of 121 consecutive patients underwent pancreatoduodenectomy for ampullary adenocarcinoma from 2006 to 2016 at Mayo Clinic in Rochester, MN. All patients were confirmed by independent pathologic review to have ampullary carcinoma. Patient survival and its correlation with patient and tumor variables were evaluated by univariate and multivariate analysis. RESULTS: Fifty three patients (45%) received adjuvant therapy (34 patients had chemotherapy alone, while 19 patients received both chemotherapy and radiation therapy). Fifty seven percent of the patients were diagnosed with advanced stage disease (Stage IIB or higher). Nearly all patients (98.3%) had negative surgical margins. Median overall survival (OS) was 91.8 months (95% CI:52.6 months-not reached). In multivariate analysis, excellent performance status (ECOG: 0), adjuvant therapy, and advanced stage remained statistically significant. Adjuvant therapy was independently associated with improved disease free survival (Hazard ratio [HR]:0.52, P = 0.04) and overall survival (HR:0.45, P = 0.03) in patients with advanced disease. CONCLUSIONS: Adjuvant therapy was associated with improved survival in patients with resected ampullary cancer, especially with advanced stage disease. A multi-institutional randomized trial is needed to further assess the role of adjuvant therapy in ampullary adenocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surveillance epidemiology end results seer database review epidemiology outcome ampullary cancer compared cholangiocarcinoma background ampullary adenocarcinoma ac rare form cancer sparse epidemiological survival data literature aimed study epidemiology survival outcome ac compared cholangiocarcinoma cc reviewing seer database methods seer database version 8 1 2 reviewed patients pts histologically confirmed ac cc 1973 2007 variables included age race gender surgical resection primary tumor seer adjusted stage overall survival os primary outcome 3 year os data analyzed using chi square kaplan meier method using z test results total 3 179 pts ac 5273 cc included seer database 1973 2007 mean age ac higher 67 5 compared 64 7 years cc p value 0 0001 ac higher white black ratio 13 1 compared cc 10 1 p value 0 0016 male female ratio similar groups stage frequency presentation ac localized 23 regional 65 distant 12 cc 22 36 42 respectively p value 0 0001 surgery rate higher ac compared cc localized 64 versus 36 p value 0 0001 regional 82 versus 35 p value 0 0001 distant stages 22 versus 13 p value 0 0001 compared stage stage pts ac better 3 year os localized 43 versus 21 regional 43 versus 12 distant disease 3 9 versus 2 6 compared cc pts surgical treatment ac still better 3 year os localized 68 versus 59 p value 0 0001 regional 44 versus 28 p value 0 0001 distant disease 12 versus 9 p value 0 45 conclusions ac compared cc statistical significant difference age race distribution compared stage stage ac better 3 year os even adjusting potential confounders including higher surgical resection rate difference appears statistically insignificant distant stages google scholar","probabilities":0.9799733,"Title":"A Surveillance Epidemiology And End Results (Seer) Database Review Of Epidemiology And Outcome Of Ampullary Cancer Compared To Cholangiocarcinoma","Abstract":"Background: Ampullary adenocarcinoma (AC) is a rare form of cancer with sparse epidemiological and survival data in literature. We aimed to study the epidemiology and survival outcome of AC compared to Cholangiocarcinoma (CC) by reviewing the SEER database. Methods: The SEER database(version 8.1.2) was reviewed for patients (pts) with histologically confirmed AC and CC between 1973-2007. Variables included were: age, race, gender, surgical resection of primary tumor, SEER adjusted stage and overall survival (OS). Primary outcome was 3 year OS. Data was analyzed using Chi square and Kaplan-Meier method using z-test. Results: A total of 3,179 pts with AC and 5273 with CC were included in SEER database between 1973 and 2007. The mean age in AC was higher 67.5 compared to 64.7 years in CC(P value=<0.0001). AC had higher white to black ratio (13:1) compared to CC (10:1) (P value=0.0016). Male to female ratio was similar in both groups. Stage frequency at presentation in AC were localized (23%), regional (65%) and distant (12%) where in CC they were 22%, 36% and 42%, respectively (P value=<0.0001). Surgery rate was higher in AC compared to CC in localized (64 versus 36%, P value=<0.0001), regional (82 versus 35%, P value=<0.0001) and distant stages (22% versus 13%, P value=<0.0001). When compared stage to stage for all pts, AC had better 3 year OS in localized (43% versus 21%), regional (43% versus 12%) and distant disease (3.9% versus 2.6%) as compared to CC. In pts who had surgical treatment, AC still had better 3 year OS in localized (68 versus 59%, P-value=<0.0001), regional (44 versus 28%, P-value=<0.0001) and distant disease (12 versus 9%, P-value=0.45). Conclusions: AC as compared with CC, has statistical significant difference in age and race distribution. When compared stage to stage, AC has a better 3 year OS even after adjusting for potential confounders including the higher surgical resection rate. This difference appears to be statistically insignificant in distant stages.","Source":"Google Scholar","category":"HUMAN","training_data":"A Surveillance Epidemiology And End Results (Seer) Database Review Of Epidemiology And Outcome Of Ampullary Cancer Compared To Cholangiocarcinoma Background: Ampullary adenocarcinoma (AC) is a rare form of cancer with sparse epidemiological and survival data in literature. We aimed to study the epidemiology and survival outcome of AC compared to Cholangiocarcinoma (CC) by reviewing the SEER database. Methods: The SEER database(version 8.1.2) was reviewed for patients (pts) with histologically confirmed AC and CC between 1973-2007. Variables included were: age, race, gender, surgical resection of primary tumor, SEER adjusted stage and overall survival (OS). Primary outcome was 3 year OS. Data was analyzed using Chi square and Kaplan-Meier method using z-test. Results: A total of 3,179 pts with AC and 5273 with CC were included in SEER database between 1973 and 2007. The mean age in AC was higher 67.5 compared to 64.7 years in CC(P value=<0.0001). AC had higher white to black ratio (13:1) compared to CC (10:1) (P value=0.0016). Male to female ratio was similar in both groups. Stage frequency at presentation in AC were localized (23%), regional (65%) and distant (12%) where in CC they were 22%, 36% and 42%, respectively (P value=<0.0001). Surgery rate was higher in AC compared to CC in localized (64 versus 36%, P value=<0.0001), regional (82 versus 35%, P value=<0.0001) and distant stages (22% versus 13%, P value=<0.0001). When compared stage to stage for all pts, AC had better 3 year OS in localized (43% versus 21%), regional (43% versus 12%) and distant disease (3.9% versus 2.6%) as compared to CC. In pts who had surgical treatment, AC still had better 3 year OS in localized (68 versus 59%, P-value=<0.0001), regional (44 versus 28%, P-value=<0.0001) and distant disease (12 versus 9%, P-value=0.45). Conclusions: AC as compared with CC, has statistical significant difference in age and race distribution. When compared stage to stage, AC has a better 3 year OS even after adjusting for potential confounders including the higher surgical resection rate. This difference appears to be statistically insignificant in distant stages. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"increasing incidence cholangiocarcinoma crete 2002 2013 introduction epidemiological data cholangiocarcinoma greece limited crete homogeneous population environmental factors uniform aims methods patients cholangiocarcinoma resident island crete diagnosed 2002 2013 two reference centers studied periampullary tumors excluded data prospectively retrospectively collected database 2 major hospitals crete crude incidence rates presented statistical analysis performed spss 19 software results 12 year period total 89 patients 55 6 males median age 74 years diagnosed cholangiocarcinoma 7 cholangiocarcinoma intrahepatic ducts 42 hilar klatskin tumors 40 patients diagnosed extrahepatic ducts carcinoma diagnosis radiologically established 91 cases 40 mrcp 28 ct 20 ercp 3 ptc histological diagnosis available 8 9 patients steady incidence increase cholangiocarcinoma irrespective location shown estimated incidence rate per three year period progressively increased 1 33 1 996 4 99 6 48 per 100 000 periods 2002 2004 2005 2007 2008 2010 2011 2013 respectively median survival time 7 months se 1 76 95 ci 3 53 10 46 median survival times according location 3 months se 2 61 intrahepatic 6 months se 1 4 klatskin tumors 11 months se 1 88 bile duct carcinomas conclusion steady incidence increase cholangiocarcinoma cases crete time period 2002 2013 shown probably due changing dietary habits since genetic background environmental factors island less stable google scholar","probabilities":0.9799733,"Title":"Increasing Incidence Of Cholangiocarcinoma In Crete 2002-2013","Abstract":"INTRODUCTION: Epidemiological data on cholangiocarcinoma in Greece is\nlimited. Crete has a homogeneous population and environmental factors are\nuniform.\nAIMS & METHODS: Patients with cholangiocarcinoma, resident on the island\nof Crete, diagnosed between 2002 and 2013 in the two reference centers, were\nstudied. Periampullary tumors were excluded. Data were prospectively and retrospectively\ncollected from the database of the 2 major hospitals of Crete. Crude\nincidence rates are presented. The statistical analysis was performed with the\nSPSS 19 software.\nRESULTS: During the 12-year period a total of 89 patients (55.6% males,\nmedian age 74 years) were diagnosed with cholangiocarcinoma. 7 of them had\ncholangiocarcinoma of the intrahepatic ducts, 42 were hilar Klatskin tumors and\n40 patients were diagnosed with extrahepatic ducts carcinoma. Diagnosis was\nradiologically established in 91% of the cases (40% MRCP, 28% CT, 20%\nERCP, 3% PTC), while histological diagnosis was available in 8 (9%) patients.\nA steady incidence increase of cholangiocarcinoma, irrespective of location, was shown. The estimated incidence rate per three-year period progressively increased\nfrom 1.33 to 1.996 to 4.99 and 6.48 per 100.000 for the periods 2002-2004, 2005-\n2007, 2008-2010 and 2011-2013 respectively. Median survival time was 7 months\n[SE 1.76 95% CI 3.53-10.46]. Median survival times according to location were 3\nmonths [SE 2.61] for intrahepatic, 6 months [SE 1.4] for Klatskin tumors and 11\nmonths [SE 1.88] for bile duct carcinomas.\nCONCLUSION: A steady incidence increase of cholangiocarcinoma cases in\nCrete during the time period 2002-2013 was shown. This is probably due to\nchanging dietary habits since both the genetic background and other environmental\nfactors in the island are more or less stable.","Source":"Google Scholar","category":"HUMAN","training_data":"Increasing Incidence Of Cholangiocarcinoma In Crete 2002-2013 INTRODUCTION: Epidemiological data on cholangiocarcinoma in Greece is\nlimited. Crete has a homogeneous population and environmental factors are\nuniform.\nAIMS & METHODS: Patients with cholangiocarcinoma, resident on the island\nof Crete, diagnosed between 2002 and 2013 in the two reference centers, were\nstudied. Periampullary tumors were excluded. Data were prospectively and retrospectively\ncollected from the database of the 2 major hospitals of Crete. Crude\nincidence rates are presented. The statistical analysis was performed with the\nSPSS 19 software.\nRESULTS: During the 12-year period a total of 89 patients (55.6% males,\nmedian age 74 years) were diagnosed with cholangiocarcinoma. 7 of them had\ncholangiocarcinoma of the intrahepatic ducts, 42 were hilar Klatskin tumors and\n40 patients were diagnosed with extrahepatic ducts carcinoma. Diagnosis was\nradiologically established in 91% of the cases (40% MRCP, 28% CT, 20%\nERCP, 3% PTC), while histological diagnosis was available in 8 (9%) patients.\nA steady incidence increase of cholangiocarcinoma, irrespective of location, was shown. The estimated incidence rate per three-year period progressively increased\nfrom 1.33 to 1.996 to 4.99 and 6.48 per 100.000 for the periods 2002-2004, 2005-\n2007, 2008-2010 and 2011-2013 respectively. Median survival time was 7 months\n[SE 1.76 95% CI 3.53-10.46]. Median survival times according to location were 3\nmonths [SE 2.61] for intrahepatic, 6 months [SE 1.4] for Klatskin tumors and 11\nmonths [SE 1.88] for bile duct carcinomas.\nCONCLUSION: A steady incidence increase of cholangiocarcinoma cases in\nCrete during the time period 2002-2013 was shown. This is probably due to\nchanging dietary habits since both the genetic background and other environmental\nfactors in the island are more or less stable. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"novel anticancer alkaloid tiliacorinine induces sustained activation extracellular signal regulated kinase synergizes cisplatin cholangiocarcinoma cells cholangiocarcinoma cca fatal cancer poor prognosis less 10 cca patients offered surgical cure conventional chemotherapy results unfavorable outcomes present plant derived compounds gaining interest potential cancer therapeutics particularly treatment refractory cancers study tiliacorinine alkaloid isolated medicinal plant tiliacora triandra colebr diels investigated anticancer activity human cca cells tiliacorinine significantly inhibited proliferation cca cells ic50 6 7 m demonstrated using srb assay flow cytometry analysis showed sub g1 phase accumulation time dependent fashion tiliacorinine induced sustained phosphorylation erk1 2 order achieve synergistic therapeutic effect reduce toxicity minimize drug resistance combined treatment tiliacorinine four conventional chemotherapeutic drugs determined using isobologram combination index ci method combined treatment tiliacorinine cisplatin resulted synergistic growth inhibition lowest ci 0 3 0 7 summary tiliacorinine suppressed growth cca cells inducing apoptosis sustaining erk activation synergizing cytotoxicity cisplatin results indicate anticancer potential tiliacorinine human cca google scholar","probabilities":0.8684211,"Title":"A Novel Anticancer Alkaloid Tiliacorinine Induces Sustained Activation Of The Extracellular Signal-Regulated Kinase And Synergizes With Cisplatin In Cholangiocarcinoma Cells","Abstract":"Cholangiocarcinoma (CCA) is a fatal cancer with poor\nprognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in\nunfavorable outcomes. At present, plant-derived compounds\nare gaining interest as potential cancer therapeutics,\nparticularly for treatment-refractory cancers. In this study,\ntiliacorinine, an alkaloid isolated from a medicinal plant,\nTiliacora triandra (Colebr.) Diels, was investigated for\nanticancer activity against human CCA cells. Tiliacorinine\nsignificantly inhibited proliferation of CCA cells with an\nIC50 of 6-7 μM as demonstrated using the SRB assay. Flow\ncytometry analysis showed sub-G1 phase accumulation in a\ntime-dependent fashion. Tiliacorinine induced sustained\nphosphorylation of ERK1/2. In order to achieve a synergistic\ntherapeutic effect, reduce toxicity and minimize the drug’s\nresistance, combined treatment between tiliacorinine and\nfour conventional chemotherapeutic drugs was determined\nusing isobologram and combination index (CI) method.\nCombined treatment between tiliacorinine and cisplatin\nresulted in synergistic growth inhibition with the lowest\nCI=0.3-0.7. In summary, tiliacorinine suppressed growth of\nCCA cells by inducing apoptosis, sustaining ERK activation\nand synergizing cytotoxicity of cisplatin. These results\nindicate the anticancer potential of tiliacorinine against\nhuman CCA.","Source":"Google Scholar","category":"ANIMAL","training_data":"A Novel Anticancer Alkaloid Tiliacorinine Induces Sustained Activation Of The Extracellular Signal-Regulated Kinase And Synergizes With Cisplatin In Cholangiocarcinoma Cells Cholangiocarcinoma (CCA) is a fatal cancer with poor\nprognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in\nunfavorable outcomes. At present, plant-derived compounds\nare gaining interest as potential cancer therapeutics,\nparticularly for treatment-refractory cancers. In this study,\ntiliacorinine, an alkaloid isolated from a medicinal plant,\nTiliacora triandra (Colebr.) Diels, was investigated for\nanticancer activity against human CCA cells. Tiliacorinine\nsignificantly inhibited proliferation of CCA cells with an\nIC50 of 6-7 μM as demonstrated using the SRB assay. Flow\ncytometry analysis showed sub-G1 phase accumulation in a\ntime-dependent fashion. Tiliacorinine induced sustained\nphosphorylation of ERK1/2. In order to achieve a synergistic\ntherapeutic effect, reduce toxicity and minimize the drug’s\nresistance, combined treatment between tiliacorinine and\nfour conventional chemotherapeutic drugs was determined\nusing isobologram and combination index (CI) method.\nCombined treatment between tiliacorinine and cisplatin\nresulted in synergistic growth inhibition with the lowest\nCI=0.3-0.7. In summary, tiliacorinine suppressed growth of\nCCA cells by inducing apoptosis, sustaining ERK activation\nand synergizing cytotoxicity of cisplatin. These results\nindicate the anticancer potential of tiliacorinine against\nhuman CCA. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"assessment clinical outcomes advanced hilar cholangiocarcinoma background low resectability poor survival outcome common hilar cholangiocarcinoma hcca especially advanced stages present study assess clinical outcome advanced hcca focusing therapeutic modalities survival analysis prognostic assessment methods clinical data 176 advanced hcca patients treated hospital january 2013 december 2015 analyzed retrospectively prognostic effects clinicopathological factors explored univariate multivariate analysis survival predictors evaluated receiver operating characteristic roc curve results 3 year overall survival rate 13 patients advanced hcca preoperative total bilirubin p 0 009 hepatic artery invasion p 0 014 treatment modalities p 0 020 independent prognostic factors overall survival model combining independent prognostic factors area roc curve 0 748 95 ci 0 678 0 811 sensitivity 82 3 specificity 53 5 highly predictive tumor death r0 resection 3 year overall survival 38 preoperative total bilirubin still independent negative factor hepatic artery invasion conclusions surgery still best treatment advanced hcca preoperative biliary drainage performed highly jaundiced patients improve survival prediction survival improved significantly model incorporates preoperative total bilirubin hepatic artery invasion treatment modalities pubmed","probabilities":0.9799733,"Title":"Assessment of clinical outcomes of advanced hilar cholangiocarcinoma","Abstract":"BACKGROUND: Low resectability and poor survival outcome are common for hilar cholangiocarcinoma (HCCA), especially in advanced stages. The present study was to assess the clinical outcome of advanced HCCA, focusing on therapeutic modalities, survival analysis and prognostic assessment. METHODS: Clinical data of 176 advanced HCCA patients who had been treated in our hospital between January 2013 and December 2015 were analyzed retrospectively. Prognostic effects of clinicopathological factors were explored by univariate and multivariate analysis. Survival predictors were evaluated by the receiver operating characteristic (ROC) curve. RESULTS: The 3-year overall survival rate was 13% for patients with advanced HCCA. Preoperative total bilirubin (P = 0.009), hepatic artery invasion (P = 0.014) and treatment modalities (P = 0.020) were independent prognostic factors on overall survival. A model combining these independent prognostic factors (area under ROC curve: 0.748; 95% CI: 0.678-0.811; sensitivity: 82.3%, specificity: 53.5%) was highly predictive of tumor death. After R0 resection, the 3-year overall survival was up to 38%. Preoperative total bilirubin was still an independent negative factor, but not for hepatic artery invasion. CONCLUSIONS: Surgery is still the best treatment for advanced HCCA. Preoperative biliary drainage should be performed in highly-jaundiced patients to improve survival. Prediction of survival is improved significantly by a model that incorporates preoperative total bilirubin, hepatic artery invasion and treatment modalities.","Source":"PubMed","category":"HUMAN","training_data":"Assessment of clinical outcomes of advanced hilar cholangiocarcinoma BACKGROUND: Low resectability and poor survival outcome are common for hilar cholangiocarcinoma (HCCA), especially in advanced stages. The present study was to assess the clinical outcome of advanced HCCA, focusing on therapeutic modalities, survival analysis and prognostic assessment. METHODS: Clinical data of 176 advanced HCCA patients who had been treated in our hospital between January 2013 and December 2015 were analyzed retrospectively. Prognostic effects of clinicopathological factors were explored by univariate and multivariate analysis. Survival predictors were evaluated by the receiver operating characteristic (ROC) curve. RESULTS: The 3-year overall survival rate was 13% for patients with advanced HCCA. Preoperative total bilirubin (P = 0.009), hepatic artery invasion (P = 0.014) and treatment modalities (P = 0.020) were independent prognostic factors on overall survival. A model combining these independent prognostic factors (area under ROC curve: 0.748; 95% CI: 0.678-0.811; sensitivity: 82.3%, specificity: 53.5%) was highly predictive of tumor death. After R0 resection, the 3-year overall survival was up to 38%. Preoperative total bilirubin was still an independent negative factor, but not for hepatic artery invasion. CONCLUSIONS: Surgery is still the best treatment for advanced HCCA. Preoperative biliary drainage should be performed in highly-jaundiced patients to improve survival. Prediction of survival is improved significantly by a model that incorporates preoperative total bilirubin, hepatic artery invasion and treatment modalities. PubMed","prediction_labels":"HUMAN"},{"cleaned":"glasgow prognostic score accurately predicts survival patients biliary tract cancer indicated surgical resection glasgow prognostic score gps neutrophil lymphocyte ratio nlr associated survival patients various types malignancy aim study investigate prognostic value gps nlr patients biliary tract cancer btc undergoing palliative chemotherapy best supportive care bsc fifty two patients newly diagnosed btc retrospectively evaluated investigated correlation gps nlr overall survival rates area receiver operating characteristics curve auc calculated compare predictive ability score univariate multivariate analyses performed identify clinicopathological variables associated overall survival significant differences gps groups regarding neutrophil levels p 0 0001 hb p 0 024 alb p 0 0001 crp p 0 0001 significant difference overall survival found groups stratified based gps nlr p 0 001 gps higher auc value 0 905 comparison nlr 0 648 multivariate analysis sex p 0 002 ca19 9 p 0 0001 gps p 0 0001 found independently associated overall survival results demonstrate gps independent marker prognosis patients btc undergoing palliative chemotherapy bsc superior nlr terms prognostic ability pubmed","probabilities":0.9799733,"Title":"The Glasgow Prognostic Score accurately predicts survival in patients with biliary tract cancer not indicated for surgical resection","Abstract":"The Glasgow Prognostic Score (GPS) and neutrophil to lymphocyte ratio (NLR) are associated with the survival in patients with various types of malignancy. The aim of this study was to investigate the prognostic value of the GPS and NLR in patients with biliary tract cancer (BTC) undergoing palliative chemotherapy or best supportive care (BSC). Fifty-two patients with newly diagnosed BTC were retrospectively evaluated. We investigated the correlation between the GPS, NLR, and the overall survival rates. The area under the receiver operating characteristics curve (AUC) was calculated to compare the predictive ability of each score. Both the univariate and multivariate analyses were performed to identify clinicopathological variables associated with the overall survival. There were significant differences between the GPS groups regarding the neutrophil levels (p < 0.0001), Hb (p = 0.024), Alb (p < 0.0001) and CRP (p < 0.0001). A significant difference in the overall survival was found between the groups stratified based on the GPS, NLR (p < 0.001). The GPS had a higher AUC value (0.905) in comparison to the NLR (0.648). In the multivariate analysis, the sex (p = 0.002), CA19-9 (p < 0.0001) and the GPS (p < 0.0001) were found to be independently associated with the overall survival. Our results demonstrate that the GPS is an independent marker of the prognosis in patients with BTC undergoing palliative chemotherapy or BSC, and is superior to the NLR in terms of its prognostic ability.","Source":"PubMed","category":"HUMAN","training_data":"The Glasgow Prognostic Score accurately predicts survival in patients with biliary tract cancer not indicated for surgical resection The Glasgow Prognostic Score (GPS) and neutrophil to lymphocyte ratio (NLR) are associated with the survival in patients with various types of malignancy. The aim of this study was to investigate the prognostic value of the GPS and NLR in patients with biliary tract cancer (BTC) undergoing palliative chemotherapy or best supportive care (BSC). Fifty-two patients with newly diagnosed BTC were retrospectively evaluated. We investigated the correlation between the GPS, NLR, and the overall survival rates. The area under the receiver operating characteristics curve (AUC) was calculated to compare the predictive ability of each score. Both the univariate and multivariate analyses were performed to identify clinicopathological variables associated with the overall survival. There were significant differences between the GPS groups regarding the neutrophil levels (p < 0.0001), Hb (p = 0.024), Alb (p < 0.0001) and CRP (p < 0.0001). A significant difference in the overall survival was found between the groups stratified based on the GPS, NLR (p < 0.001). The GPS had a higher AUC value (0.905) in comparison to the NLR (0.648). In the multivariate analysis, the sex (p = 0.002), CA19-9 (p < 0.0001) and the GPS (p < 0.0001) were found to be independently associated with the overall survival. Our results demonstrate that the GPS is an independent marker of the prognosis in patients with BTC undergoing palliative chemotherapy or BSC, and is superior to the NLR in terms of its prognostic ability. PubMed","prediction_labels":"HUMAN"},{"cleaned":"systemic immune inflammation index predicts prognosis intrahepatic cholangiocarcinoma international multi institutional analysis background objective study examine whether systemic immune inflammation index sii associated prognosis among patients following resection intrahepatic cholangiocarcinoma icc methods impact sii overall os cancer specific survival css following resection icc assessed performance final multivariable models incorporated inflammatory markers e neutrophil lymphocyte ratio nlr platelet lymphocyte ratio plr sii platelets nlr assessed using harrell concordance index results patients high sii worse 5 year os 37 7 vs 46 6 p 0 001 css 46 1 vs 50 1 p 0 001 compared patients low sii elevated sii hr 1 70 95 ci 1 23 2 34 nlr hr 1 58 95 ci 1 10 2 27 independently predicted worse os whereas high plr hr 1 17 95 ci 0 85 1 60 longer associated prognosis sii remained independent predictor css hr 1 55 95 ci 1 09 2 21 sii multivariable model outperformed models incorporated plr nlr relative os c index 0 696 vs 0 689 vs 0 692 css c index 0 697 vs 0 689 vs 0 690 conclusion sii independently predicted os css among patients resectable icc sii may better predictor outcomes compared markers inflammatory response among patients resectable icc stn","probabilities":0.9799733,"Title":"The Systemic Immune-Inflammation Index Predicts Prognosis In Intrahepatic Cholangiocarcinoma: An International Multi-Institutional Analysis","Abstract":"Background: The objective of this study was to examine whether the systemic immune inflammation index (SII) was associated with prognosis among patients following resection of intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: The impact of SII on overall (OS) and cancer-specific survival (CSS) following resection of ICC was assessed. The performance of the final multivariable models that incorporated inflammatory markers (i.e. neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR] and SII [platelets∗NLR]) was assessed using the Harrell's concordance index. \r\n\r\n Results: Patients with high SII had worse 5-year OS (37.7% vs 46.6%, p < 0.001) and CSS (46.1% vs 50.1%, p < 0.001) compared with patients with low SII. An elevated SII (HR = 1.70, 95% CI 1.23-2.34) and NLR (HR = 1.58, 95% CI 1.10-2.27) independently predicted worse OS, whereas high PLR (HR = 1.17, 95% CI 0.85-1.60) was no longer associated with prognosis. Only SII remained an independent predictor of CSS (HR = 1.55, 95% CI 1.09-2.21). The SII multivariable model outperformed models that incorporated PLR and NLR relative to OS (c-index; 0.696 vs 0.689 vs 0.692) and CSS (c-index; 0.697 vs 0.689 vs 0.690). \r\n\r\n Conclusion: SII independently predicted OS and CSS among patients with resectable ICC. SII may be a better predictor of outcomes compared with other markers of inflammatory response among patients with resectable ICC.","Source":"STN","category":"HUMAN","training_data":"The Systemic Immune-Inflammation Index Predicts Prognosis In Intrahepatic Cholangiocarcinoma: An International Multi-Institutional Analysis Background: The objective of this study was to examine whether the systemic immune inflammation index (SII) was associated with prognosis among patients following resection of intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: The impact of SII on overall (OS) and cancer-specific survival (CSS) following resection of ICC was assessed. The performance of the final multivariable models that incorporated inflammatory markers (i.e. neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte ratio [PLR] and SII [platelets∗NLR]) was assessed using the Harrell's concordance index. \r\n\r\n Results: Patients with high SII had worse 5-year OS (37.7% vs 46.6%, p < 0.001) and CSS (46.1% vs 50.1%, p < 0.001) compared with patients with low SII. An elevated SII (HR = 1.70, 95% CI 1.23-2.34) and NLR (HR = 1.58, 95% CI 1.10-2.27) independently predicted worse OS, whereas high PLR (HR = 1.17, 95% CI 0.85-1.60) was no longer associated with prognosis. Only SII remained an independent predictor of CSS (HR = 1.55, 95% CI 1.09-2.21). The SII multivariable model outperformed models that incorporated PLR and NLR relative to OS (c-index; 0.696 vs 0.689 vs 0.692) and CSS (c-index; 0.697 vs 0.689 vs 0.690). \r\n\r\n Conclusion: SII independently predicted OS and CSS among patients with resectable ICC. SII may be a better predictor of outcomes compared with other markers of inflammatory response among patients with resectable ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"abdominal obesity weight gain adulthood risk liver biliary tract cancer european cohort general obesity positively associated risk liver probably biliary tract cancer little known abdominal obesity weight gain adulthood used multivariable cox proportional hazard models investigate associations weight body mass index waist hip circumference waist hip waist height ratio whtr weight change adulthood risk hepatocellular carcinoma hcc intrahepatic ibdc extrahepatic bile duct system cancer ebdsc including gallbladder cancer gbc among 359 525 men women european prospective investigation cancer nutrition study hepatitis b c virus status measured nested case control subset mean follow 8 6 years 177 cases hcc 58 cases ibdc 210 cases ebdsc including 76 cases gbc occurred anthropometric measures positively associated risk hcc gbc whtr showed strongest association hcc relative risk rr comparing extreme tertiles 3 51 95 confidence interval 95 ci 2 09 5 87 p trend 0 0001 gbc rr 1 56 95 ci 1 12 2 16 increment one unit whtr weight gain adulthood also positively associated hcc comparing extreme tertiles rr 2 48 95 ci 1 49 4 13 0 001 statistically significant association observed obesity risk ibdc ebdsc results provide evidence association obesity particularly abdominal obesity risk hcc gbc findings support public health recommendations reduce prevalence obesity weight gain adulthood hcc gbc prevention western populations pubmed","probabilities":0.9799733,"Title":"Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort","Abstract":"General obesity has been positively associated with risk of liver and probably with biliary tract cancer, but little is known about abdominal obesity or weight gain during adulthood. We used multivariable Cox proportional hazard models to investigate associations between weight, body mass index, waist and hip circumference, waist-to-hip and waist-to-height ratio (WHtR), weight change during adulthood and risk of hepatocellular carcinoma (HCC), intrahepatic (IBDC) and extrahepatic bile duct system cancer [EBDSC including gallbladder cancer (GBC)] among 359,525 men and women in the European Prospective Investigation into Cancer and Nutrition study. Hepatitis B and C virus status was measured in a nested case-control subset. During a mean follow-up of 8.6 years, 177 cases of HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC, occurred. All anthropometric measures were positively associated with risk of HCC and GBC. WHtR showed the strongest association with HCC [relative risk (RR) comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.09-5.87; p(trend) < 0.0001] and with GBC (RR: 1.56, 95% CI: 1.12-2.16 for an increment of one unit in WHtR). Weight gain during adulthood was also positively associated with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.49-4.13; <0.001). No statistically significant association was observed between obesity and risk of IBDC and EBDSC. Our results provide evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC. Our findings support public health recommendations to reduce the prevalence of obesity and weight gain in adulthood for HCC and GBC prevention in Western populations.","Source":"PubMed","category":"HUMAN","training_data":"Abdominal obesity, weight gain during adulthood and risk of liver and biliary tract cancer in a European cohort General obesity has been positively associated with risk of liver and probably with biliary tract cancer, but little is known about abdominal obesity or weight gain during adulthood. We used multivariable Cox proportional hazard models to investigate associations between weight, body mass index, waist and hip circumference, waist-to-hip and waist-to-height ratio (WHtR), weight change during adulthood and risk of hepatocellular carcinoma (HCC), intrahepatic (IBDC) and extrahepatic bile duct system cancer [EBDSC including gallbladder cancer (GBC)] among 359,525 men and women in the European Prospective Investigation into Cancer and Nutrition study. Hepatitis B and C virus status was measured in a nested case-control subset. During a mean follow-up of 8.6 years, 177 cases of HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC, occurred. All anthropometric measures were positively associated with risk of HCC and GBC. WHtR showed the strongest association with HCC [relative risk (RR) comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.09-5.87; p(trend) < 0.0001] and with GBC (RR: 1.56, 95% CI: 1.12-2.16 for an increment of one unit in WHtR). Weight gain during adulthood was also positively associated with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.49-4.13; <0.001). No statistically significant association was observed between obesity and risk of IBDC and EBDSC. Our results provide evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC. Our findings support public health recommendations to reduce the prevalence of obesity and weight gain in adulthood for HCC and GBC prevention in Western populations. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pre operative biliary drainage associated shortened survival time patients cholangiocarcinoma background objective although pre operative biliary drainage pbd frequently performed patients cholangiocarcinoma cca impact patient survival unclear aim evaluate impact pbd overall survival patients extra hepatic cca methods retrospective study using surveillance epidemiology end results seer medicare data patients underwent biliary drainage within 3 months prior diagnosis cca included pbd cohort patients receive biliary drainage included non pbd cohort cox proportional hazard regression used determine independent predictors survival results 3862 patients extra hepatic cca 433 11 2 underwent curative surgical resection median survival 14 months 95 confidence interval 95 ci 10 21 months pbd cohort n 126 vs 31 months 95 ci 26 39 months non pbd cohort n 307 p 0 001 median follow duration surgical cohort 26 months range 1 60 months among 433 patients 126 29 1 underwent pbd significantly higher charlson comorbidity index advanced seer stage without pbd surgery multivariable analysis patients underwent curative surgical resection adjusting patient demographics tumor characteristics charlson comorbidity index radiotherapy chemotherapy pbd significantly associated shortened survival time hazard ratio 2 35 95 ci 1 34 4 10 p 0 003 conclusions pbd appears negative impact long term survival patients potentially resectable cca avoided possible stn","probabilities":0.9799733,"Title":"Pre-Operative Biliary Drainage Is Associated With Shortened Survival Time In Patients With Cholangiocarcinoma","Abstract":"Background and objective: Although pre-operative biliary drainage (PBD) is frequently performed in patients with cholangiocarcinoma (CCA), its impact on patient survival is unclear. Our aim was to evaluate the impact of PBD on overall survival of patients with extra-hepatic CCA. \r\n\r\n Methods: This was a retrospective study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Patients who underwent biliary drainage within 3 months prior to and/or after diagnosis of CCA were included in the PBD cohort. Patients who did not receive biliary drainage were included in the non-PBD cohort. Cox proportional hazard regression was used to determine independent predictors of survival. \r\n\r\n Results: Of 3862 patients with extra-hepatic CCA, 433 (11.2%) underwent curative surgical resection, with a median survival of 14 months (95% confidence interval [95% CI], 10-21 months) in the PBD cohort (n = 126) vs 31 months (95% CI, 26-39 months) in the non-PBD cohort (n = 307) (P < 0.001), during the median follow-up duration for the surgical cohort of 26 months (range, 1-60 months). Among the 433 patients, 126 (29.1%) underwent PBD and had significantly higher Charlson comorbidity index and advanced SEER stage than those without PBD before surgery. On multivariable analysis in patients who underwent curative surgical resection, after adjusting patient demographics, tumor characteristics, Charlson comorbidity index, radiotherapy and chemotherapy, PBD was significantly associated with shortened survival time (hazard ratio, 2.35; 95% CI, 1.34-4.10; P = 0.003). \r\n\r\n Conclusions: PBD appears negative impact on long-term survival in patients with potentially resectable CCA and should be avoided if possible.","Source":"STN","category":"HUMAN","training_data":"Pre-Operative Biliary Drainage Is Associated With Shortened Survival Time In Patients With Cholangiocarcinoma Background and objective: Although pre-operative biliary drainage (PBD) is frequently performed in patients with cholangiocarcinoma (CCA), its impact on patient survival is unclear. Our aim was to evaluate the impact of PBD on overall survival of patients with extra-hepatic CCA. \r\n\r\n Methods: This was a retrospective study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare data. Patients who underwent biliary drainage within 3 months prior to and/or after diagnosis of CCA were included in the PBD cohort. Patients who did not receive biliary drainage were included in the non-PBD cohort. Cox proportional hazard regression was used to determine independent predictors of survival. \r\n\r\n Results: Of 3862 patients with extra-hepatic CCA, 433 (11.2%) underwent curative surgical resection, with a median survival of 14 months (95% confidence interval [95% CI], 10-21 months) in the PBD cohort (n = 126) vs 31 months (95% CI, 26-39 months) in the non-PBD cohort (n = 307) (P < 0.001), during the median follow-up duration for the surgical cohort of 26 months (range, 1-60 months). Among the 433 patients, 126 (29.1%) underwent PBD and had significantly higher Charlson comorbidity index and advanced SEER stage than those without PBD before surgery. On multivariable analysis in patients who underwent curative surgical resection, after adjusting patient demographics, tumor characteristics, Charlson comorbidity index, radiotherapy and chemotherapy, PBD was significantly associated with shortened survival time (hazard ratio, 2.35; 95% CI, 1.34-4.10; P = 0.003). \r\n\r\n Conclusions: PBD appears negative impact on long-term survival in patients with potentially resectable CCA and should be avoided if possible. STN","prediction_labels":"HUMAN"},{"cleaned":"managing incidentally detected gallbladder cancer algorithms controversies introduction gallbladder cancer gbc fifth common neoplasm gastrointestinal tract common cancer biliary tract gbc suspected preoperatively 30 40 patients 60 70 discovered incidentally igbc pathologist gallbladder specimen following cholecystectomy benign diseases polyps gallstones cholecystitis materials methods 1995 2011 30 cases gbc underwent resection curative intent institutions retrospectively reviewed analyzed demographic data type operation surgical morbidity mortality histopathological classification survival incidental gbc compared suspected preoperatively diagnosed gbc overall survival disease free survival dfs difference dfs patients previously treated laparoscopic cholecystectomy oncological resection first intervention analyzed authors also present systematic review evaluate role extended surgery treatment incidental gbc results gbc diagnosed 30 patients 16 women 14 men m f ratio 1 1 14 mean age 69 4 years range 45 83 years preoperative diagnosis possible 14 cases fourteen incidental cases diagnosed postoperatively pathological examination two suspected intraoperatively opening surgical specimen confirmed frozen sections ratio incidental nonincidental cases 1 14 1 twelve cases discovered laparoscopic cholecystectomy eighty one per cent incidental cases discovered early stage ii preoperative diagnosis 30 patients gbc gbc liver invasion diagnosed preoperative ct nine cases gallbladder abscess perforated hepatic parenchyma involving transversal mesocolon hepatic hilum one case porcelain gallbladder three cases gallbladder adenoma four cases chronic cholecystolithiasis thirteen cases every case except one t1b advanced invasion underwent ivb v wedge liver resection pericholedochic hepatoduodenal lymphoadenectomy one patient refused surgery cases tis t1a involvement treated cholecystectomy alone nine sixteen patients incidental diagnosis reached 5 year dfs 56 25 eight recurrence free surprisingly one patient reached 38 mo survival despite port site recurrence one experience 2 years original surgery requiring resection cases non incidental diagnosis locally advanced two patients experienced 5 years dfs tables 2 3 conclusion laparoscopic cholecystectomy affect survival implemented properly reoperation two objectives r0 resection clearance lymph nodes pubmed","probabilities":0.9799733,"Title":"Managing the incidentally detected gallbladder cancer: algorithms and controversies","Abstract":"INTRODUCTION: Gallbladder cancer (GBC) is the fifth most common neoplasm of the gastrointestinal tract and the most common cancer of the biliary tract. GBC is suspected preoperatively in only 30-40% of patients. The other 60-70% are discovered incidentally (IGBC) by the pathologist on a gallbladder specimen following cholecystectomy for benign diseases such as polyps, gallstones, and cholecystitis. MATERIALS AND METHODS: Between 1995 and 2011, 30 cases of GBC, who underwent resection with curative intent in our institutions, were retrospectively reviewed. They were analyzed for demographic data, and type of operation, surgical morbidity and mortality, histopathological classification, and survival. Incidental GBC was compared with suspected or preoperatively diagnosed GBC. Overall survival, disease-free survival (DFS) and the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention were analyzed. The authors also present a systematic review to evaluate the role of extended surgery in the treatment of the incidental GBC. RESULTS: GBC was diagnosed in 30 patients, 16 women and 14 men. The M/F ratio was 1:1.14 and the mean age was 69.4 years (range 45-83 years). A preoperative diagnosis was possible only in 14 cases; fourteen of the incidental cases were diagnosed postoperatively after the pathological examination; two were suspected intraoperatively at the opening of the surgical specimen and then confirmed by frozen sections. The ratio between incidental and nonincidental cases was 1, 14/1, with twelve cases discovered after laparoscopic cholecystectomy. Eighty-one per cent of the incidental cases were discovered at an early stage (≤II). The preoperative diagnosis of the 30 patients with GBC was: GBC with liver invasion diagnosed by preoperative CT (nine cases); gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum (one case); porcelain gallbladder (three cases); gallbladder adenoma (four cases); and chronic cholecystolithiasis (thirteen cases). Every case, except one, with a T1b or more advanced invasion underwent IVb + V wedge liver resection and pericholedochic/hepatoduodenal lymphoadenectomy. One patient refused further surgery. Cases with Tis and T1a involvement were treated with cholecystectomy alone. Nine of the sixteen patients with incidental diagnosis reached 5-year DFS (56.25%) and eight of them are recurrence free. Surprisingly, one patient reached 38 mo survival despite a port-site recurrence (the only one in our experience) 2 years after the original surgery requiring further resection. Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5 years DFS (Tables 2 and 3). CONCLUSION: Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes.","Source":"PubMed","category":"HUMAN","training_data":"Managing the incidentally detected gallbladder cancer: algorithms and controversies INTRODUCTION: Gallbladder cancer (GBC) is the fifth most common neoplasm of the gastrointestinal tract and the most common cancer of the biliary tract. GBC is suspected preoperatively in only 30-40% of patients. The other 60-70% are discovered incidentally (IGBC) by the pathologist on a gallbladder specimen following cholecystectomy for benign diseases such as polyps, gallstones, and cholecystitis. MATERIALS AND METHODS: Between 1995 and 2011, 30 cases of GBC, who underwent resection with curative intent in our institutions, were retrospectively reviewed. They were analyzed for demographic data, and type of operation, surgical morbidity and mortality, histopathological classification, and survival. Incidental GBC was compared with suspected or preoperatively diagnosed GBC. Overall survival, disease-free survival (DFS) and the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention were analyzed. The authors also present a systematic review to evaluate the role of extended surgery in the treatment of the incidental GBC. RESULTS: GBC was diagnosed in 30 patients, 16 women and 14 men. The M/F ratio was 1:1.14 and the mean age was 69.4 years (range 45-83 years). A preoperative diagnosis was possible only in 14 cases; fourteen of the incidental cases were diagnosed postoperatively after the pathological examination; two were suspected intraoperatively at the opening of the surgical specimen and then confirmed by frozen sections. The ratio between incidental and nonincidental cases was 1, 14/1, with twelve cases discovered after laparoscopic cholecystectomy. Eighty-one per cent of the incidental cases were discovered at an early stage (≤II). The preoperative diagnosis of the 30 patients with GBC was: GBC with liver invasion diagnosed by preoperative CT (nine cases); gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum (one case); porcelain gallbladder (three cases); gallbladder adenoma (four cases); and chronic cholecystolithiasis (thirteen cases). Every case, except one, with a T1b or more advanced invasion underwent IVb + V wedge liver resection and pericholedochic/hepatoduodenal lymphoadenectomy. One patient refused further surgery. Cases with Tis and T1a involvement were treated with cholecystectomy alone. Nine of the sixteen patients with incidental diagnosis reached 5-year DFS (56.25%) and eight of them are recurrence free. Surprisingly, one patient reached 38 mo survival despite a port-site recurrence (the only one in our experience) 2 years after the original surgery requiring further resection. Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5 years DFS (Tables 2 and 3). CONCLUSION: Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"therapeutic index associated lymphadenectomy among patients intrahepatic cholangiocarcinoma patients benefit nodal evaluation background although lymph node metastasis lnm important prognostic indicator patients intrahepatic cholangiocarcinoma icc benefit indication lymphadenectomy remain unclear methods patients diagnosed icc 1990 2016 identified international multi institutional dataset determine survival benefit lymphadenectomy therapeutic index calculated multiplying frequency lnm particular group patients 3 year cancer specific survival css rate patients lnm subgroup results among 471 patients met inclusion criteria approximately half lnm n 205 43 5 median number resected metastatic lns 4 interquartile range iqr 2 8 0 iqr 0 1 respectively three year css entire cohort 29 9 reflecting therapeutic index value 13 0 therapeutic index lower among patients major vascular invasion 5 4 preoperative carcinoembryonic antigen cea 5 0 8 2 lnm areas hepatoduodenal ligament 5 2 note therapeutic index difference 10 points noted examining number lns harvested 1 2 4 1 vs 3 6 16 1 vs 7 17 8 conclusion survival benefit derived lymphadenectomy poor among patients major vascular invasion cea 5 0 lnm areas hepatoduodenal ligament resection three lns associated highest therapeutic value among patients lnm pubmed","probabilities":0.9799733,"Title":"Therapeutic Index Associated with Lymphadenectomy Among Patients with Intrahepatic Cholangiocarcinoma: Which Patients Benefit the Most from Nodal Evaluation?","Abstract":"BACKGROUND: Although lymph node metastasis (LNM) is an important prognostic indicator for patients with intrahepatic cholangiocarcinoma (ICC), the benefit and indication for lymphadenectomy remain unclear. METHODS: Patients diagnosed with ICC between 1990 and 2016 were identified in the international multi-institutional dataset. To determine the survival benefit from lymphadenectomy, the therapeutic index was calculated by multiplying the frequency of LNM in a particular group of patients by the 3-year cancer-specific survival (CSS) rate of patients with LNM in that subgroup. RESULTS: Among 471 patients who met the inclusion criteria, approximately half had LNM (n = 205, 43.5%). The median number of resected and metastatic LNs were 4 [interquartile range (IQR) 2-8] and 0 (IQR 0-1), respectively. Three-year CSS in the entire cohort was 29.9%, reflecting a therapeutic index value of 13.0. The therapeutic index was lower among patients with major vascular invasion (5.4), preoperative carcinoembryonic antigen (CEA) > 5.0 (8.2), and LNM in areas other than the hepatoduodenal ligament (5.2). Of note, a therapeutic index difference of more than 10 points was noted only when examining the number of LNs harvested [1-2 (4.1) vs. 3-6 (16.1) vs. ≥ 7 (17.8)]. CONCLUSION: The survival benefit derived from lymphadenectomy was poor among patients with major vascular invasion, CEA > 5.0, and LNM in areas other than the hepatoduodenal ligament. Resection of three or more LNs was associated with the highest therapeutic value among patients with LNM.","Source":"PubMed","category":"HUMAN","training_data":"Therapeutic Index Associated with Lymphadenectomy Among Patients with Intrahepatic Cholangiocarcinoma: Which Patients Benefit the Most from Nodal Evaluation? BACKGROUND: Although lymph node metastasis (LNM) is an important prognostic indicator for patients with intrahepatic cholangiocarcinoma (ICC), the benefit and indication for lymphadenectomy remain unclear. METHODS: Patients diagnosed with ICC between 1990 and 2016 were identified in the international multi-institutional dataset. To determine the survival benefit from lymphadenectomy, the therapeutic index was calculated by multiplying the frequency of LNM in a particular group of patients by the 3-year cancer-specific survival (CSS) rate of patients with LNM in that subgroup. RESULTS: Among 471 patients who met the inclusion criteria, approximately half had LNM (n = 205, 43.5%). The median number of resected and metastatic LNs were 4 [interquartile range (IQR) 2-8] and 0 (IQR 0-1), respectively. Three-year CSS in the entire cohort was 29.9%, reflecting a therapeutic index value of 13.0. The therapeutic index was lower among patients with major vascular invasion (5.4), preoperative carcinoembryonic antigen (CEA) > 5.0 (8.2), and LNM in areas other than the hepatoduodenal ligament (5.2). Of note, a therapeutic index difference of more than 10 points was noted only when examining the number of LNs harvested [1-2 (4.1) vs. 3-6 (16.1) vs. ≥ 7 (17.8)]. CONCLUSION: The survival benefit derived from lymphadenectomy was poor among patients with major vascular invasion, CEA > 5.0, and LNM in areas other than the hepatoduodenal ligament. Resection of three or more LNs was associated with the highest therapeutic value among patients with LNM. PubMed","prediction_labels":"HUMAN"},{"cleaned":"common factors involved pathogenesis primary intrahepatic epithelial cancers meta analysis emerging risk factors intrahepatic cholangiocarcinoma background aims well established risk factors intrahepatic cholangiocarcinoma biliary tract inflammation liver flukes present western countries patients although cirrhosis causes chronic liver disease implicated contribution risk factors cholangiocarcinoma unclear aims analyze emerging potential risk factors systematic examination case control series geographically diverse regions methods performed literature review meta analysis case control studies intrahepatic cholangiocarcinoma cirrhosis related risk factors tests heterogeneity publication bias sensitivity analyses performed overall odds ratio 95 confidence intervals calculated results eleven studies high low prevalence regions identified studies except evaluating cirrhosis diabetes obesity exhibited significant heterogeneity cirrhosis associated combined 22 92 95 ci 18 24 28 79 meta analysis estimated overall odds ratio 95 confidence intervals defined risk factors hepatitis b 5 10 2 91 8 95 hepatitis c 4 84 2 41 9 71 obesity 1 56 1 26 1 94 diabetes mellitus type ii 1 89 1 74 2 07 smoking 1 31 0 95 1 82 alcohol use 2 81 1 52 5 21 sensitivity analysis alter odds ratio risk factors except smoking evidence publication bias conclusions cirrhosis chronic hepatitis b c alcohol use diabetes obesity major risk factors intrahepatic cholangiocarcinoma data suggest common pathogenesis primary intrahepatic epithelial cancers stn","probabilities":0.9799733,"Title":"Are Common Factors Involved In The Pathogenesis Of Primary Intrahepatic Epithelial Cancers? A Meta-Analysis Of Emerging Risk Factors For Intrahepatic Cholangiocarcinoma","Abstract":"Background & aims: Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions. \n\n Methods: We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated. \n\n Results: Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias. \n\n Conclusions: Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers.","Source":"STN","category":"HUMAN","training_data":"Are Common Factors Involved In The Pathogenesis Of Primary Intrahepatic Epithelial Cancers? A Meta-Analysis Of Emerging Risk Factors For Intrahepatic Cholangiocarcinoma Background & aims: Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions. \n\n Methods: We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated. \n\n Results: Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias. \n\n Conclusions: Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers. STN","prediction_labels":"HUMAN"},{"cleaned":"complications image guided transcatheter hepatic chemoembolization primary secondary tumours liver background image guided transcatheter hepatic chemoembolization tace accepted worldwide effective treatment patients unresectable hepatocellular carcinoma hcc adequate preservation liver function although considered relatively safe tace associated several complications aim study determine prevalence complications associated tace therapy correlate certain risk factors either well known yet evaluated patients methods total 330 chemoembolization procedures performed 170 patients 117 males 53 females period 64 months retrospectively analysed among patients 123 hepatocellular carcinoma 10 intrahepatic cholangiocarcinoma 37 hepatic metastases variables considered tumour histotype bilioenteric anastomosis previous combined treatment radiofrequency thermal ablation antibiotic prophylaxis chemotherapeutic agents use new drug eluting microspheres comorbidities diabetes patient age presence vascular anatomical variations results total 30 complications occurred 27 procedures total complication rate per procedure 9 1 approximately 75 patients postembolization syndrome difference prevalence complications statistically significant group diabetic patients 13 3 compared remaining patients 6 3 p 0 002 patients biliary stents 25 compared without stents 7 75 p 0 027 conclusion data show diabetes mellitus presence bilioenteric anastomosis risk factors developing complications tace use new drug eluting microspheres increase risk complications pubmed","probabilities":0.9799733,"Title":"Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver","Abstract":"BACKGROUND: Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC) and for adequate preservation of liver function. Although considered relatively safe, TACE has been associated with several complications. The aim of this study was to determine the prevalence of the complications associated with TACE therapy and to correlate it with certain risk factors, either well-known or not yet evaluated. PATIENTS AND METHODS: A total of 330 chemoembolization procedures performed in 170 patients (117 males and 53 females) over a period of 64 months were retrospectively analysed. Among the patients, 123 had hepatocellular carcinoma, 10 had intrahepatic cholangiocarcinoma and 37 had hepatic metastases. The variables considered were: tumour histotype, bilioenteric anastomosis, previous or combined treatment with radiofrequency thermal ablation, antibiotic prophylaxis, chemotherapeutic agents, use of new drug-eluting microspheres, comorbidities such as diabetes, patient age and the presence of vascular anatomical variations. RESULTS: A total of 30 complications occurred in 27 procedures. The total complication rate per procedure was 9.1% and approximately 75% of patients had postembolization syndrome. The difference in the prevalence of complications was statistically significant in the group of diabetic patients (13.3%) compared to the remaining patients (6.3%) (p = 0.002) and in patients with biliary stents (25%) compared to those without stents (7.75%) (p = 0.027). CONCLUSION: These data show that diabetes mellitus and the presence of bilioenteric anastomosis are risk factors for developing complications after TACE. The use of new drug-eluting microspheres did not increase the risk of complications.","Source":"PubMed","category":"HUMAN","training_data":"Complications of image-guided transcatheter hepatic chemoembolization of primary and secondary tumours of the liver BACKGROUND: Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC) and for adequate preservation of liver function. Although considered relatively safe, TACE has been associated with several complications. The aim of this study was to determine the prevalence of the complications associated with TACE therapy and to correlate it with certain risk factors, either well-known or not yet evaluated. PATIENTS AND METHODS: A total of 330 chemoembolization procedures performed in 170 patients (117 males and 53 females) over a period of 64 months were retrospectively analysed. Among the patients, 123 had hepatocellular carcinoma, 10 had intrahepatic cholangiocarcinoma and 37 had hepatic metastases. The variables considered were: tumour histotype, bilioenteric anastomosis, previous or combined treatment with radiofrequency thermal ablation, antibiotic prophylaxis, chemotherapeutic agents, use of new drug-eluting microspheres, comorbidities such as diabetes, patient age and the presence of vascular anatomical variations. RESULTS: A total of 30 complications occurred in 27 procedures. The total complication rate per procedure was 9.1% and approximately 75% of patients had postembolization syndrome. The difference in the prevalence of complications was statistically significant in the group of diabetic patients (13.3%) compared to the remaining patients (6.3%) (p = 0.002) and in patients with biliary stents (25%) compared to those without stents (7.75%) (p = 0.027). CONCLUSION: These data show that diabetes mellitus and the presence of bilioenteric anastomosis are risk factors for developing complications after TACE. The use of new drug-eluting microspheres did not increase the risk of complications. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance pre operative inflammatory markers resected gallbladder cancer systematic review background neutrophil lymphocyte ratio nlr c reactive protein crp glasgow prognostic score gps demonstrated good prognostic value several cancers role gallbladder cancer gbc remains unclear aim study systematically review current literature determine role predicting survival outcomes gbc methods using pre specified inclusive search strategy medline embase cinahl databases used identify studies describing survival patients gbc resection high low pre operative crp gps nlr proforma used extract study author date number patients age gender tumour stage use adjuvant therapy primary outcome data results 46 studies identified initial screening four studies reporting survival outcomes studies described reduction survival patients elevated nlr gps crp three studies showed nlr independent prognostic marker one study additionally demonstrated elevated crp gps associated poorer survival conclusions elevated pre operative inflammatory markers inversely related survival outcomes relatively inexpensive easy measurable parameters aid decision making process involved management gbc sub stratification groups utilizing inflammatory markers may help guide surgical strategy however studies retrospective low moderate quality high quality prospective studies well defined inclusion criteria outcomes needed guide role inflammatory markers management gbc pubmed","probabilities":0.9799733,"Title":"Prognostic significance of pre-operative inflammatory markers in resected gallbladder cancer: a systematic review","Abstract":"BACKGROUND: Neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP) and Glasgow Prognostic Score (GPS) have demonstrated good prognostic value in several cancers but their role in gallbladder cancer (GBC) remains unclear. The aim of this study is to systematically review the current literature to determine their role in predicting survival outcomes in GBC. METHODS: Using a pre-specified inclusive search strategy MEDLINE, EMBASE and CINAHL databases were used to identify studies describing survival in patients after GBC resection with high or low pre-operative CRP, GPS or NLR. A proforma was used to extract study author and date, number of patients, age, gender, tumour stage, use of adjuvant therapy and primary outcome data. RESULTS: In all, 46 studies were identified after initial screening with four studies reporting survival outcomes. All studies described a reduction in survival in patients with an elevated NLR, GPS or CRP. Three studies showed NLR to be an independent prognostic marker and one study additionally demonstrated that elevated CRP and GPS were associated with poorer survival. CONCLUSIONS: Elevated pre-operative inflammatory markers are inversely related to survival outcomes. They are relatively inexpensive, easy measurable parameters that could aid in the decision making process involved in the management of GBC. Sub-stratification of groups utilizing inflammatory markers may help guide surgical strategy. However, these studies are retrospective and of low to moderate quality. High quality, prospective studies with well-defined inclusion criteria and outcomes are needed to guide the role of inflammatory markers in the management of GBC.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of pre-operative inflammatory markers in resected gallbladder cancer: a systematic review BACKGROUND: Neutrophil to lymphocyte ratio (NLR), C-reactive protein (CRP) and Glasgow Prognostic Score (GPS) have demonstrated good prognostic value in several cancers but their role in gallbladder cancer (GBC) remains unclear. The aim of this study is to systematically review the current literature to determine their role in predicting survival outcomes in GBC. METHODS: Using a pre-specified inclusive search strategy MEDLINE, EMBASE and CINAHL databases were used to identify studies describing survival in patients after GBC resection with high or low pre-operative CRP, GPS or NLR. A proforma was used to extract study author and date, number of patients, age, gender, tumour stage, use of adjuvant therapy and primary outcome data. RESULTS: In all, 46 studies were identified after initial screening with four studies reporting survival outcomes. All studies described a reduction in survival in patients with an elevated NLR, GPS or CRP. Three studies showed NLR to be an independent prognostic marker and one study additionally demonstrated that elevated CRP and GPS were associated with poorer survival. CONCLUSIONS: Elevated pre-operative inflammatory markers are inversely related to survival outcomes. They are relatively inexpensive, easy measurable parameters that could aid in the decision making process involved in the management of GBC. Sub-stratification of groups utilizing inflammatory markers may help guide surgical strategy. However, these studies are retrospective and of low to moderate quality. High quality, prospective studies with well-defined inclusion criteria and outcomes are needed to guide the role of inflammatory markers in the management of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"high expression hif 1a bnip3 pi3kc3 hypoxia induced autophagy predicts cholangiocarcinoma survival metastasis hypoxia autophagy known facilitate tumor progression aimed investigate role hypoxia associated autophagy cholangiocarcinoma cca survival metastasis immunostaining hypoxic responsive proteins hif 1 bnip3 key regulator autophagy pi3kc3 examined cca tissues expression levels compared clinicopathological parameters hypoxia mimicking condition cocl2 treatment also tested regarding cca cell functions results showed hif 1 66 bnip3 44 pi3kc3 46 showed strong staining human cca tissues positive expression hif 1 p 0 033 bnip3 p 0 040 pi3kc3 p 0 037 significantly correlated lymph node metastasis hif 1 well associated bnip3 r 0 3 p 0 01 pi3kc3 r 0 2 p 0 01 survival rates patients positive hif 1 p 0 047 co expressed hif 1 bnip3 p 0 032 hif 1 pi3kc3 p 0 043 significantly greater negative groups cca cells treated cocl2 showed increase hif 1 bnip3 pi3kc3 lc3 ii increased cell migration pfak levels data suggest hypoxia associated autophagy enhances cca metastasis resulting poor prognosis cca stn","probabilities":0.9467213,"Title":"High Expression Of Hif-1A Bnip3 And Pi3Kc3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival And Metastasis","Abstract":"Hypoxia and autophagy are known to facilitate tumor progression. We here aimed to investigate the role of hypoxia-associated autophagy in cholangiocarcinoma (CCA) survival and metastasis. Immunostaining of hypoxic- responsive proteins (HIF-1α and BNIP3) and a key regulator of autophagy (PI3KC3) were examined in CCA tissues and their expression levels were compared with clinicopathological parameters. A hypoxia mimicking condition (CoCl2 treatment) was also tested regarding CCA cell functions. Our results showed that HIF-1α (66%), BNIP3 (44%) and PI3KC3 (46%) showed strong staining in human CCA tissues. Positive expression of HIF-1α (p=0.033), BNIP3 (p=0.040) and PI3KC3 (p=0.037) was significantly correlated with lymph node metastasis. HIF-1α was well associated with BNIP3 (r=0.3, p<0.01) and PI3KC3 (r=0.2, p<0.01). The survival rates of patients who were positive with HIF-1α (p=0.047) or co-expressed HIF-1α and BNIP3 (p=0.032) or HIF-1α and PI3KC3 (p=0.043) were significantly greater than in the negative groups. CCA cells treated with CoCl2 showed an increase in HIF-1α, BNIP3, PI3KC3 and LC3-II, with increased cell migration and pFAK levels. These data suggest that hypoxia associated autophagy enhances CCA metastasis, resulting in a poor prognosis of CCA.","Source":"STN","category":"ANIMAL","training_data":"High Expression Of Hif-1A Bnip3 And Pi3Kc3: Hypoxia-Induced Autophagy Predicts Cholangiocarcinoma Survival And Metastasis Hypoxia and autophagy are known to facilitate tumor progression. We here aimed to investigate the role of hypoxia-associated autophagy in cholangiocarcinoma (CCA) survival and metastasis. Immunostaining of hypoxic- responsive proteins (HIF-1α and BNIP3) and a key regulator of autophagy (PI3KC3) were examined in CCA tissues and their expression levels were compared with clinicopathological parameters. A hypoxia mimicking condition (CoCl2 treatment) was also tested regarding CCA cell functions. Our results showed that HIF-1α (66%), BNIP3 (44%) and PI3KC3 (46%) showed strong staining in human CCA tissues. Positive expression of HIF-1α (p=0.033), BNIP3 (p=0.040) and PI3KC3 (p=0.037) was significantly correlated with lymph node metastasis. HIF-1α was well associated with BNIP3 (r=0.3, p<0.01) and PI3KC3 (r=0.2, p<0.01). The survival rates of patients who were positive with HIF-1α (p=0.047) or co-expressed HIF-1α and BNIP3 (p=0.032) or HIF-1α and PI3KC3 (p=0.043) were significantly greater than in the negative groups. CCA cells treated with CoCl2 showed an increase in HIF-1α, BNIP3, PI3KC3 and LC3-II, with increased cell migration and pFAK levels. These data suggest that hypoxia associated autophagy enhances CCA metastasis, resulting in a poor prognosis of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"linc01410 promotes cell proliferation migration cholangiocarcinoma modulating mir 124 3p smad5 axis background cholangiocarcinoma cca generally associated high incidence poor prognosis nowadays increasing experimental data demonstrate long non coding rna lncrna plays indispensable role tumor occurrence nevertheless specific mechanism lncrna clear cca methods relative expressions lncrnas mirnas mrnas detected real time quantitative pcr rt qpcr cck8 colony formation assays applied examine cell proliferation ability cca transwell assay conducted measure migration invasion capabilities cca cells nuclear cytoplasmic separation assay implemented figure location linc01410 luciferase reporter assay rip rna pull assays applied certify molecular bindings western blot applied detect protein level results high expression linc01410 proved cca tissues cca cell lines also cca patients high linc01410 level presented poor prognosis linc01410 deficiency impeded cell proliferation migration invasion hucct1 rbe cell lines linc01410 interacted mir 124 3p meanwhile smad5 targeted inhibited mir 124 3p smad5 expression enhanced linc01410 conclusion linc01410 facilitates cell proliferation migration invasion mir 124 3p smad5 axis stn","probabilities":0.9467213,"Title":"Linc01410 Promotes Cell Proliferation And Migration Of Cholangiocarcinoma Through Modulating Mir-124-3P/Smad5 Axis","Abstract":"Background: Cholangiocarcinoma (CCA) is generally associated with high incidence and poor prognosis. Nowadays, increasing experimental data demonstrate that long non-coding RNA (lncRNA) plays an indispensable role in tumor occurrence. Nevertheless, the specific mechanism of lncRNA is not clear in CCA. \r\n\r\n Methods: The relative expressions of lncRNAs, miRNAs, and mRNAs were detected by real-time quantitative PCR (RT-qPCR). CCK8 and colony formation assays were applied to examine cell proliferation ability in CCA. Transwell assay was conducted to measure the migration and invasion capabilities of CCA cells. Nuclear and cytoplasmic separation assay was implemented to figure out the location of LINC01410. Luciferase reporter assay, RIP and RNA pull-down assays were applied to certify the molecular bindings. Western blot was applied to detect the protein level. \r\n\r\n Results: The high expression of LINC01410 was proved in CCA tissues and CCA cell lines. Also, CCA patients with high LINC01410 level presented poor prognosis. LINC01410 deficiency impeded cell proliferation, migration and invasion in HuCCT1 and RBE cell lines. What's more, LINC01410 interacted with miR-124-3p. Meanwhile, SMAD5 targeted and inhibited by miR-124-3p. SMAD5 expression was enhanced by LINC01410. \r\n\r\n Conclusion: LINC01410 facilitates cell proliferation, migration and invasion through miR-124-3p/SMAD5 axis.","Source":"STN","category":"ANIMAL","training_data":"Linc01410 Promotes Cell Proliferation And Migration Of Cholangiocarcinoma Through Modulating Mir-124-3P/Smad5 Axis Background: Cholangiocarcinoma (CCA) is generally associated with high incidence and poor prognosis. Nowadays, increasing experimental data demonstrate that long non-coding RNA (lncRNA) plays an indispensable role in tumor occurrence. Nevertheless, the specific mechanism of lncRNA is not clear in CCA. \r\n\r\n Methods: The relative expressions of lncRNAs, miRNAs, and mRNAs were detected by real-time quantitative PCR (RT-qPCR). CCK8 and colony formation assays were applied to examine cell proliferation ability in CCA. Transwell assay was conducted to measure the migration and invasion capabilities of CCA cells. Nuclear and cytoplasmic separation assay was implemented to figure out the location of LINC01410. Luciferase reporter assay, RIP and RNA pull-down assays were applied to certify the molecular bindings. Western blot was applied to detect the protein level. \r\n\r\n Results: The high expression of LINC01410 was proved in CCA tissues and CCA cell lines. Also, CCA patients with high LINC01410 level presented poor prognosis. LINC01410 deficiency impeded cell proliferation, migration and invasion in HuCCT1 and RBE cell lines. What's more, LINC01410 interacted with miR-124-3p. Meanwhile, SMAD5 targeted and inhibited by miR-124-3p. SMAD5 expression was enhanced by LINC01410. \r\n\r\n Conclusion: LINC01410 facilitates cell proliferation, migration and invasion through miR-124-3p/SMAD5 axis. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic impact peritumoral il 17 positive cells il 17 axis patients intrahepatic cholangiocarcinoma background development cancer linked inflammatory cytokines interleukin il 6 il 17 study assessed expression cytokines intrahepatic cholangiocarcinoma icc determined correlation survival probability methods total 72 consecutive patients underwent curative resection icc osaka university hospital march 1998 november 2014 enrolled immunohistochemical analysis performed il 17 receptor il 17ra well il 6 enzyme linked immunosorbent assay elisa performed preoperative plasma levels il 6 il 17 32 patients icc results immunohistochemical analysis showed il 6 high n 34 il 17ra high n 29 groups significantly worse disease free survival dfs il 6 low n 38 il 17ra low n 43 groups respectively although il 17 cells abundant intratumoral area patients high peritumoral intratumoral il 17 cells n 28 corresponded significantly lower overall survival os dfs os p 0 023 dfs p 0 026 low group moreover multivariate cox proportional hazards analysis revealed il 6 peritumoral il 17 il 17ra independent prognostic factors dfs p 0 023 p 0 0088 p 0 039 respectively addition high preoperative plasma levels il 6 patients icc corresponded significantly lower dfs p 0 002 conclusions data suggested il 6 peritumoral il 17 cells il 17ra expression postoperative useful markers predicting recurrence patients icc pubmed","probabilities":0.9799733,"Title":"Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: Development of cancer has been linked to inflammatory cytokines such as interleukin (IL)-6 and IL-17. In this study, we assessed the expression of these cytokines in intrahepatic cholangiocarcinoma (ICC) and determined their correlation to the survival probability. METHODS: A total of 72 consecutive patients who underwent curative resection of ICC at Osaka University Hospital from March 1998 to November 2014 were enrolled. Immunohistochemical analysis was performed for IL-17 and its receptor A (IL-17RA), as well as IL-6. Enzyme-linked immunosorbent assay (ELISA) was performed for preoperative plasma levels of IL-6 and IL-17 in 32 patients with ICC. RESULTS: Immunohistochemical analysis showed that the IL-6(high) (n = 34) and IL-17RA(high) (n = 29) groups had significantly worse disease-free survival (DFS) than IL-6(low) (n = 38) and IL-17RA(low) (n = 43) groups, respectively. Although IL-17(+) cells were abundant in the intratumoral area, patients with high peritumoral, but not intratumoral, IL-17(+) cells (n = 28) corresponded with a significantly lower overall survival (OS) and DFS (OS, p = 0.023; DFS, p = 0.026) than those with low group. Moreover, multivariate Cox proportional hazards analysis revealed that IL-6, peritumoral IL-17(+), and IL-17RA are independent prognostic factors for DFS (p = 0.023, p = 0.0088, p = 0.039, respectively). In addition, high preoperative plasma levels of IL-6 in patients with ICC corresponded with significantly lower DFS (p = 0.002). CONCLUSIONS: Our data suggested that IL-6, peritumoral IL-17(+) cells, and IL-17RA expression are postoperative useful markers for predicting recurrence in patients with ICC.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Impact of Peritumoral IL-17-Positive Cells and IL-17 Axis in Patients with Intrahepatic Cholangiocarcinoma BACKGROUND: Development of cancer has been linked to inflammatory cytokines such as interleukin (IL)-6 and IL-17. In this study, we assessed the expression of these cytokines in intrahepatic cholangiocarcinoma (ICC) and determined their correlation to the survival probability. METHODS: A total of 72 consecutive patients who underwent curative resection of ICC at Osaka University Hospital from March 1998 to November 2014 were enrolled. Immunohistochemical analysis was performed for IL-17 and its receptor A (IL-17RA), as well as IL-6. Enzyme-linked immunosorbent assay (ELISA) was performed for preoperative plasma levels of IL-6 and IL-17 in 32 patients with ICC. RESULTS: Immunohistochemical analysis showed that the IL-6(high) (n = 34) and IL-17RA(high) (n = 29) groups had significantly worse disease-free survival (DFS) than IL-6(low) (n = 38) and IL-17RA(low) (n = 43) groups, respectively. Although IL-17(+) cells were abundant in the intratumoral area, patients with high peritumoral, but not intratumoral, IL-17(+) cells (n = 28) corresponded with a significantly lower overall survival (OS) and DFS (OS, p = 0.023; DFS, p = 0.026) than those with low group. Moreover, multivariate Cox proportional hazards analysis revealed that IL-6, peritumoral IL-17(+), and IL-17RA are independent prognostic factors for DFS (p = 0.023, p = 0.0088, p = 0.039, respectively). In addition, high preoperative plasma levels of IL-6 in patients with ICC corresponded with significantly lower DFS (p = 0.002). CONCLUSIONS: Our data suggested that IL-6, peritumoral IL-17(+) cells, and IL-17RA expression are postoperative useful markers for predicting recurrence in patients with ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"curcumin mediated regulation notch1 hairy enhancer split 1 survivin molecular targeting cholangiocarcinoma background cholangiocarcinoma cca highly malignant characterized poor prognosis chemotherapeutic resistance therefore continued development novel effective approaches needed notch expression markedly upregulated cca utility notch1 inhibition defined based recent findings hypothesized curcumin polyphenolic phytochemical suppresses cca growth vitro via inhibition notch1 signaling methods established cca cell lines cclp 1 sg 231 treated varying concentrations curcumin 0 20 m viability assessed 3 4 5 dimethylthiazol 2 yl 2 5 diphenyltetrazolium bromide clonogenic assays evaluation apoptosis determined via western analysis apoptotic markers caspase glo 3 7 assay cell lysates analyzed via western blotting notch1 hes 1 survivin pathway expression cell cycle progression survival results curcumin treated cca cells exhibited reduced viability compared control treatment statistically significant reductions cell viability observed curcumin treatment concentrations 7 5 10 15 m approximately 10 48 56 cclp 1 13 25 50 sg 231 respectively western analysis concentrations 10 m showed reductions notch1 hes 1 survivin apoptosis evidenced increase expression cleaved poly adp ribose polymerase increase caspase activity cyclin d1 cell cycle progression expression levels also reduced treatment conclusions curcumin effectively induces cca cclp 1 sg 231 growth suppression apoptosis relatively low treatment concentrations compared previous research concomitant reduction notch1 hes 1 survivin expression cca cell lines provides novel evidence potential antitumorigenic mechanism action knowledge first report showing reduction hes 1 expression via protein analysis treatment curcumin findings merit investigation curcumin mediated inhibition notch signaling cca either alone combination chemotherapeutic agents pubmed","probabilities":0.875,"Title":"Curcumin-mediated regulation of Notch1/hairy and enhancer of split-1/survivin: molecular targeting in cholangiocarcinoma","Abstract":"BACKGROUND: Cholangiocarcinoma (CCA) is highly malignant and characterized by poor prognosis with chemotherapeutic resistance. Therefore, continued development of novel, effective approaches are needed. Notch expression is markedly upregulated in CCA, but the utility of Notch1 inhibition is not defined. Based on recent findings, we hypothesized that curcumin, a polyphenolic phytochemical, suppresses CCA growth in vitro via inhibition of Notch1 signaling. METHODS: Established CCA cell lines CCLP-1 and SG-231 were treated with varying concentrations of curcumin (0-20 μM). Viability was assessed through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and clonogenic assays. Evaluation of apoptosis was determined via Western analysis for apoptotic markers and Caspase-Glo 3/7 assay. Cell lysates were further analyzed via Western blotting for Notch1/HES-1/survivin pathway expression, cell cycle progression, and survival. RESULTS: Curcumin-treated CCA cells exhibited reduced viability compared with control treatment. Statistically significant reductions in cell viability were observed with curcumin treatment at concentrations of 7.5, 10, and 15 μM by approximately 10%, 48%, and 56% for CCLP-1 and 13%, 25%, and 50% for SG-231, respectively. On Western analysis, concentrations of ≥10 μM showed reductions in Notch1, HES-1, and survivin. Apoptosis was evidenced by an increase in expression of cleaved poly [ADP] ribose polymerase and an increase in caspase activity. Cyclin D1 (cell cycle progression) expression levels were also reduced with treatment. CONCLUSIONS: Curcumin effectively induces CCA (CCLP-1 and SG-231) growth suppression and apoptosis at relatively low treatment concentrations when compared with the previous research. A concomitant reduction of Notch1, HES-1, and survivin expression in CCA cell lines provides novel evidence for a potential antitumorigenic mechanism-of-action. To our knowledge, this is the first report showing reduction in HES-1 expression via protein analysis after treatment with curcumin. Such findings merit further investigation of curcumin-mediated inhibition of Notch signaling in CCA either alone or in combination with chemotherapeutic agents.","Source":"PubMed","category":"ANIMAL","training_data":"Curcumin-mediated regulation of Notch1/hairy and enhancer of split-1/survivin: molecular targeting in cholangiocarcinoma BACKGROUND: Cholangiocarcinoma (CCA) is highly malignant and characterized by poor prognosis with chemotherapeutic resistance. Therefore, continued development of novel, effective approaches are needed. Notch expression is markedly upregulated in CCA, but the utility of Notch1 inhibition is not defined. Based on recent findings, we hypothesized that curcumin, a polyphenolic phytochemical, suppresses CCA growth in vitro via inhibition of Notch1 signaling. METHODS: Established CCA cell lines CCLP-1 and SG-231 were treated with varying concentrations of curcumin (0-20 μM). Viability was assessed through 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide and clonogenic assays. Evaluation of apoptosis was determined via Western analysis for apoptotic markers and Caspase-Glo 3/7 assay. Cell lysates were further analyzed via Western blotting for Notch1/HES-1/survivin pathway expression, cell cycle progression, and survival. RESULTS: Curcumin-treated CCA cells exhibited reduced viability compared with control treatment. Statistically significant reductions in cell viability were observed with curcumin treatment at concentrations of 7.5, 10, and 15 μM by approximately 10%, 48%, and 56% for CCLP-1 and 13%, 25%, and 50% for SG-231, respectively. On Western analysis, concentrations of ≥10 μM showed reductions in Notch1, HES-1, and survivin. Apoptosis was evidenced by an increase in expression of cleaved poly [ADP] ribose polymerase and an increase in caspase activity. Cyclin D1 (cell cycle progression) expression levels were also reduced with treatment. CONCLUSIONS: Curcumin effectively induces CCA (CCLP-1 and SG-231) growth suppression and apoptosis at relatively low treatment concentrations when compared with the previous research. A concomitant reduction of Notch1, HES-1, and survivin expression in CCA cell lines provides novel evidence for a potential antitumorigenic mechanism-of-action. To our knowledge, this is the first report showing reduction in HES-1 expression via protein analysis after treatment with curcumin. Such findings merit further investigation of curcumin-mediated inhibition of Notch signaling in CCA either alone or in combination with chemotherapeutic agents. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"jq1 induces dna damage apoptosis inhibits tumor growth patient derived xenograft model cholangiocarcinoma cholangiocarcinoma cca fatal disease 5 year survival 30 majority patients chemotherapy therapeutic option virtually patients relapse gemcitabine first line agent treatment cca patients treated gemcitabine monotherapy survive 8 months combining agent cisplatin increases survival 3 months neither regimen produces durable remissions molecular etiology disease poorly understood facilitate molecular characterization development effective therapies cca established panel patient derived xenograft pdx models cca used two models investigate antitumor efficacy mechanism action bromodomain inhibitor jq1 agent evaluated treatment cca data show jq1 suppressed growth cca pdx model cca2 demonstrate growth suppression concomitant inhibition c myc protein expression second model cca1 jq1 insensitive tumor progression c myc expression unaffected exposure agent also selective cca2 tumors jq1 induced dna damage apoptosis downregulated multiple c myc transcriptional targets regulate cell cycle progression dna repair findings suggest c myc inhibition several transcriptional targets may contribute mechanism action jq1 tumor type conclude bet inhibitors jq1 warrant investigation treatment cca mol cancer ther 17 1 107 18 2017 aacr stn","probabilities":0.9467213,"Title":"Jq1 Induces Dna Damage And Apoptosis And Inhibits Tumor Growth In A Patient-Derived Xenograft Model Of Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a fatal disease with a 5-year survival of <30%. For a majority of patients, chemotherapy is the only therapeutic option, and virtually all patients relapse. Gemcitabine is the first-line agent for treatment of CCA. Patients treated with gemcitabine monotherapy survive ∼8 months. Combining this agent with cisplatin increases survival by ∼3 months, but neither regimen produces durable remissions. The molecular etiology of this disease is poorly understood. To facilitate molecular characterization and development of effective therapies for CCA, we established a panel of patient-derived xenograft (PDX) models of CCA. We used two of these models to investigate the antitumor efficacy and mechanism of action of the bromodomain inhibitor JQ1, an agent that has not been evaluated for the treatment of CCA. The data show that JQ1 suppressed the growth of the CCA PDX model CCA2 and demonstrate that growth suppression was concomitant with inhibition of c-Myc protein expression. A second model (CCA1) was JQ1-insensitive, with tumor progression and c-Myc expression unaffected by exposure to this agent. Also selective to CCA2 tumors, JQ1 induced DNA damage and apoptosis and downregulated multiple c-Myc transcriptional targets that regulate cell-cycle progression and DNA repair. These findings suggest that c-Myc inhibition and several of its transcriptional targets may contribute to the mechanism of action of JQ1 in this tumor type. We conclude that BET inhibitors such as JQ1 warrant further investigation for the treatment of CCA. Mol Cancer Ther; 17(1); 107-18. ©2017 AACR.","Source":"STN","category":"ANIMAL","training_data":"Jq1 Induces Dna Damage And Apoptosis And Inhibits Tumor Growth In A Patient-Derived Xenograft Model Of Cholangiocarcinoma Cholangiocarcinoma (CCA) is a fatal disease with a 5-year survival of <30%. For a majority of patients, chemotherapy is the only therapeutic option, and virtually all patients relapse. Gemcitabine is the first-line agent for treatment of CCA. Patients treated with gemcitabine monotherapy survive ∼8 months. Combining this agent with cisplatin increases survival by ∼3 months, but neither regimen produces durable remissions. The molecular etiology of this disease is poorly understood. To facilitate molecular characterization and development of effective therapies for CCA, we established a panel of patient-derived xenograft (PDX) models of CCA. We used two of these models to investigate the antitumor efficacy and mechanism of action of the bromodomain inhibitor JQ1, an agent that has not been evaluated for the treatment of CCA. The data show that JQ1 suppressed the growth of the CCA PDX model CCA2 and demonstrate that growth suppression was concomitant with inhibition of c-Myc protein expression. A second model (CCA1) was JQ1-insensitive, with tumor progression and c-Myc expression unaffected by exposure to this agent. Also selective to CCA2 tumors, JQ1 induced DNA damage and apoptosis and downregulated multiple c-Myc transcriptional targets that regulate cell-cycle progression and DNA repair. These findings suggest that c-Myc inhibition and several of its transcriptional targets may contribute to the mechanism of action of JQ1 in this tumor type. We conclude that BET inhibitors such as JQ1 warrant further investigation for the treatment of CCA. Mol Cancer Ther; 17(1); 107-18. ©2017 AACR. STN","prediction_labels":"ANIMAL"},{"cleaned":"major hepatectomy perihilar cholangiocarcinoma background purpose hilar cholangiocarcinoma intrahepatic cholangiocarcinoma involving hepatic hilus defined perihilar cholangiocarcinoma principle surgical treatment hemi hepatectomy trisectionectomy liver caudate lobectomy resection extrahepatic bile duct complete resection tumor aim study review outcomes major hepatectomy perihilar cholangiocarcinoma methods using kaplan meier method cox proportional hazards model analyzed results 125 patients perihilar cholangiocarcinoma undergone major hepatectomy results right hepatectomy right trisectionectomy left hepatectomy left trisectionectomy performed 66 8 49 2 patients respectively curative resection achieved 79 patients 63 2 mortality morbidity rates 8 0 48 7 respectively overall 1 3 5 year survival rates patients 73 2 36 7 34 7 respectively median survival 26 8 months multivariate analysis showed independent prognostic factors overall survival gender histopathological grading curative resection american joint committee cancer ajcc international union cancer uicc pt conclusions major hepatectomy perihilar cholangiocarcinoma acceptable showed satisfactory outcomes long term survival patients surgeon aim complete resection tumor negative margins pubmed","probabilities":0.9799733,"Title":"Major hepatectomy for perihilar cholangiocarcinoma","Abstract":"BACKGROUND/PURPOSE: Hilar cholangiocarcinoma and intrahepatic cholangiocarcinoma involving the hepatic hilus are defined as \"perihilar cholangiocarcinoma\". The principle of surgical treatment is hemi-hepatectomy or trisectionectomy of the liver, caudate lobectomy, and resection of the extrahepatic bile duct for complete resection of the tumor. The aim of this study was to review the outcomes of major hepatectomy for perihilar cholangiocarcinoma. METHODS: Using the Kaplan-Meier method and the Cox proportional hazards model, we analyzed the results in 125 patients with perihilar cholangiocarcinoma who had undergone major hepatectomy. RESULTS: Right hepatectomy, right trisectionectomy, left hepatectomy, and left trisectionectomy were performed in 66, 8, 49, and 2 patients, respectively. Curative resection was achieved in 79 patients (63.2%). Mortality and morbidity rates were 8.0 and 48.7%, respectively. The overall 1-, 3-, and 5-year survival rates of all patients were 73.2, 36.7, and 34.7%, respectively. The median survival was 26.8 months. Multivariate analysis showed that the independent prognostic factors for overall survival were gender, histopathological grading, curative resection, and American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) pT. CONCLUSIONS: Major hepatectomy for perihilar cholangiocarcinoma was acceptable and showed satisfactory outcomes. For long-term survival in these patients, the surgeon should aim for complete resection of the tumor with negative margins.","Source":"PubMed","category":"HUMAN","training_data":"Major hepatectomy for perihilar cholangiocarcinoma BACKGROUND/PURPOSE: Hilar cholangiocarcinoma and intrahepatic cholangiocarcinoma involving the hepatic hilus are defined as \"perihilar cholangiocarcinoma\". The principle of surgical treatment is hemi-hepatectomy or trisectionectomy of the liver, caudate lobectomy, and resection of the extrahepatic bile duct for complete resection of the tumor. The aim of this study was to review the outcomes of major hepatectomy for perihilar cholangiocarcinoma. METHODS: Using the Kaplan-Meier method and the Cox proportional hazards model, we analyzed the results in 125 patients with perihilar cholangiocarcinoma who had undergone major hepatectomy. RESULTS: Right hepatectomy, right trisectionectomy, left hepatectomy, and left trisectionectomy were performed in 66, 8, 49, and 2 patients, respectively. Curative resection was achieved in 79 patients (63.2%). Mortality and morbidity rates were 8.0 and 48.7%, respectively. The overall 1-, 3-, and 5-year survival rates of all patients were 73.2, 36.7, and 34.7%, respectively. The median survival was 26.8 months. Multivariate analysis showed that the independent prognostic factors for overall survival were gender, histopathological grading, curative resection, and American Joint Committee on Cancer (AJCC)/International Union Against Cancer (UICC) pT. CONCLUSIONS: Major hepatectomy for perihilar cholangiocarcinoma was acceptable and showed satisfactory outcomes. For long-term survival in these patients, the surgeon should aim for complete resection of the tumor with negative margins. PubMed","prediction_labels":"HUMAN"},{"cleaned":"occupational exposure asbestos risk cholangiocarcinoma population based case control study four nordic countries objectives assess association occupational exposure asbestos risk cholangiocarcinoma cc methods conducted case control study nested nordic occupational cancer nocca cohort studied 1458 intrahepatic cc icc 3972 extrahepatic cc ecc cases occurring among subjects born 1920 later finland iceland norway sweden case individually matched birth year gender country five population controls cumulative exposure asbestos measured fibres f ml years assessed applying nocca job exposure matrix data occupations collected national population censuses conducted 1960 1970 1980 81 1990 odds ratios 95 ci estimated using conditional logistic regression models adjusted printing industry work results observed increasing risk icc cumulative exposure asbestos never exposed 1 0 reference category 0 1 4 9 f ml years 1 1 95 ci 0 9 1 3 5 0 9 9 f ml years 1 3 95 ci 0 9 2 1 10 0 14 9 f ml years 1 6 95 ci 1 0 2 5 15 0 f ml years 1 7 95 ci 1 1 2 6 observe association cumulative asbestos exposure ecc conclusions study provides evidence exposure asbestos might risk factor icc findings also suggest association ecc asbestos null weaker observed icc studies based large industrial cohorts asbestos workers possibly accounting personal characteristics clinical history needed pubmed","probabilities":0.9799733,"Title":"Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries","Abstract":"OBJECTIVES: To assess the association between occupational exposure to asbestos and the risk of cholangiocarcinoma (CC). METHODS: We conducted a case-control study nested in the Nordic Occupational Cancer (NOCCA) cohort. We studied 1458 intrahepatic CC (ICC) and 3972 extrahepatic CC (ECC) cases occurring among subjects born in 1920 or later in Finland, Iceland, Norway and Sweden. Each case was individually matched by birth year, gender and country to five population controls. The cumulative exposure to asbestos (measured in fibres (f)/ml × years) was assessed by applying the NOCCA job-exposure matrix to data on occupations collected during national population censuses (conducted in 1960, 1970, 1980/81 and 1990). Odds ratios (OR) and 95% CI were estimated using conditional logistic regression models adjusted by printing industry work. RESULTS: We observed an increasing risk of ICC with cumulative exposure to asbestos: never exposed, OR 1.0 (reference category); 0.1-4.9 f/mL × years, OR 1.1 (95% CI 0.9 to 1.3); 5.0-9.9 f/mL × years, OR 1.3 (95% CI 0.9 to 2.1); 10.0-14.9 f/mL × years, OR 1.6 (95% CI 1.0 to 2.5); ≥15.0 f/mL × years, OR 1.7 (95% CI 1.1 to 2.6). We did not observe an association between cumulative asbestos exposure and ECC. CONCLUSIONS: Our study provides evidence that exposure to asbestos might be a risk factor for ICC. Our findings also suggest that the association between ECC and asbestos is null or weaker than that observed for ICC. Further studies based on large industrial cohorts of asbestos workers and possibly accounting for personal characteristics and clinical history are needed.","Source":"PubMed","category":"HUMAN","training_data":"Occupational exposure to asbestos and risk of cholangiocarcinoma: a population-based case-control study in four Nordic countries OBJECTIVES: To assess the association between occupational exposure to asbestos and the risk of cholangiocarcinoma (CC). METHODS: We conducted a case-control study nested in the Nordic Occupational Cancer (NOCCA) cohort. We studied 1458 intrahepatic CC (ICC) and 3972 extrahepatic CC (ECC) cases occurring among subjects born in 1920 or later in Finland, Iceland, Norway and Sweden. Each case was individually matched by birth year, gender and country to five population controls. The cumulative exposure to asbestos (measured in fibres (f)/ml × years) was assessed by applying the NOCCA job-exposure matrix to data on occupations collected during national population censuses (conducted in 1960, 1970, 1980/81 and 1990). Odds ratios (OR) and 95% CI were estimated using conditional logistic regression models adjusted by printing industry work. RESULTS: We observed an increasing risk of ICC with cumulative exposure to asbestos: never exposed, OR 1.0 (reference category); 0.1-4.9 f/mL × years, OR 1.1 (95% CI 0.9 to 1.3); 5.0-9.9 f/mL × years, OR 1.3 (95% CI 0.9 to 2.1); 10.0-14.9 f/mL × years, OR 1.6 (95% CI 1.0 to 2.5); ≥15.0 f/mL × years, OR 1.7 (95% CI 1.1 to 2.6). We did not observe an association between cumulative asbestos exposure and ECC. CONCLUSIONS: Our study provides evidence that exposure to asbestos might be a risk factor for ICC. Our findings also suggest that the association between ECC and asbestos is null or weaker than that observed for ICC. Further studies based on large industrial cohorts of asbestos workers and possibly accounting for personal characteristics and clinical history are needed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcomes prognostic factors gallbladder cancer single centre experience introduction gallbladder cancer common malignant tumour biliary system extraordinarily poor prognosis study retrospectively evaluated forty two patients histologically proven gallbladder cancer patients methods estimated survival rates calculated kaplan meier method differences assessed using logrank test gkr combined registry cancer demographic data used gain information community cancer statistics results study patients metastases showed poorer survival rates furthermore survival significantly better patients r0 resections smaller tumour sizes without lymph node infiltration stage m stage r stage independent prognostic parameters sex age significant effect survival also found patients incidental gallbladder cancer cholecystolithiasis showed significantly better survival rates demographic analyses study group confirmed high coverage institution incident cases catchment area significant regional deviations expected incidence gallbladder cancer conclusion despite differences incidence different geographical areas gallbladder cancer appears fairly normally distributed western pomerania predominantly rural area northeastern germany coverage incident cases catchment area high stage m stage r stage independent prognostic factors study conclude whenever possible r0 resection surgical goal patients staged resectable surgery heroic resections patients highly advanced cancer disease severe accompanying non tumour diseases warranted pubmed","probabilities":0.9799733,"Title":"Outcomes and prognostic factors in gallbladder cancer: a single-centre experience","Abstract":"INTRODUCTION: Gallbladder cancer is the most common malignant tumour of the biliary system with an extraordinarily poor prognosis. In this study, we retrospectively evaluated forty-two patients with histologically proven gallbladder cancer. PATIENTS AND METHODS: Estimated survival rates were calculated by the Kaplan-Meier method, and differences were assessed using the logrank test. The GKR (combined registry of cancer) and demographic data were used to gain information on community cancer statistics. RESULTS: In this study, patients with metastases showed poorer survival rates. Furthermore, the survival was significantly better in patients with R0 resections, smaller tumour sizes and without lymph node infiltration. T stage, M stage and R stage were independent prognostic parameters. Sex and age had no significant effect on survival. Also, we found that patients with incidental gallbladder cancer and those with cholecystolithiasis showed significantly better survival rates. Demographic analyses of the study group confirmed a high coverage of our institution for incident cases in our catchment area and no significant regional deviations from the expected incidence of gallbladder cancer. CONCLUSION: Despite differences in the incidence in different geographical areas, gallbladder cancer appears to be fairly normally distributed in Western Pomerania, a predominantly rural area of Northeastern Germany. Coverage of incident cases in our catchment area was high. T stage, M stage and R stage were independent prognostic factors in our study. We conclude that, whenever possible, an R0 resection should be the surgical goal in all patients staged resectable before surgery, but heroic resections in patients with highly advanced cancer disease or severe accompanying non-tumour diseases are not warranted.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes and prognostic factors in gallbladder cancer: a single-centre experience INTRODUCTION: Gallbladder cancer is the most common malignant tumour of the biliary system with an extraordinarily poor prognosis. In this study, we retrospectively evaluated forty-two patients with histologically proven gallbladder cancer. PATIENTS AND METHODS: Estimated survival rates were calculated by the Kaplan-Meier method, and differences were assessed using the logrank test. The GKR (combined registry of cancer) and demographic data were used to gain information on community cancer statistics. RESULTS: In this study, patients with metastases showed poorer survival rates. Furthermore, the survival was significantly better in patients with R0 resections, smaller tumour sizes and without lymph node infiltration. T stage, M stage and R stage were independent prognostic parameters. Sex and age had no significant effect on survival. Also, we found that patients with incidental gallbladder cancer and those with cholecystolithiasis showed significantly better survival rates. Demographic analyses of the study group confirmed a high coverage of our institution for incident cases in our catchment area and no significant regional deviations from the expected incidence of gallbladder cancer. CONCLUSION: Despite differences in the incidence in different geographical areas, gallbladder cancer appears to be fairly normally distributed in Western Pomerania, a predominantly rural area of Northeastern Germany. Coverage of incident cases in our catchment area was high. T stage, M stage and R stage were independent prognostic factors in our study. We conclude that, whenever possible, an R0 resection should be the surgical goal in all patients staged resectable before surgery, but heroic resections in patients with highly advanced cancer disease or severe accompanying non-tumour diseases are not warranted. PubMed","prediction_labels":"HUMAN"},{"cleaned":"overexpression sig1r closely associated tumor progression poor outcome patients hilar cholangiocarcinoma nonopioid sigma1 receptor sig1r regulates various metabolism functions implicated cancers yet role hilar cholangiocarcinoma remains unclear present study examined sig1r expression hilar cholangiocarcinoma hc tissues explored possible clinical values tissue microarray blocks containing 92 hc tissues matched non cancerous bile duct tissues examined immunohistochemically expression sig1r protein overexpression sig1r found 43 46 7 92 primary tumor tissues overexpression sig1r significantly associated poor undifferentiation p 0 011 tumor invasion p 0 001 lymph node metastasis p 0 047 advanced disease stage p 0 024 hc patients kaplan meier analysis showed patients overexpressing sig1r earlier recurrence worse overall survival overexpressing sig1r cox regression analysis revealed sig1r independent factor predict hc recurrence prognosis hc patients results suggest sig1r frequently activated human hc tissue overexpression sig1r might serve predictor tumor recurrence prognostic biomarker hc patients pubmed","probabilities":0.8684211,"Title":"Overexpression of Sig1R is closely associated with tumor progression and poor outcome in patients with hilar cholangiocarcinoma","Abstract":"Nonopioid Sigma1 receptor (Sig1R), which regulates various metabolism functions, has been implicated in cancers; yet, its role in hilar cholangiocarcinoma remains unclear. In the present study, we examined Sig1R expression in hilar cholangiocarcinoma (HC) tissues and explored its possible clinical values. Tissue microarray blocks containing 92 HC tissues and matched non-cancerous bile duct tissues were examined immunohistochemically for expression of Sig1R protein. Overexpression of Sig1R was found in 43 (46.7%) of the 92 primary tumor tissues. Overexpression of Sig1R was significantly associated with poor/undifferentiation (P = 0.011), tumor invasion (P = 0.001), lymph node metastasis (P = 0.047), and advanced disease stage (P = 0.024) of HC patients. Kaplan-Meier analysis showed that patients overexpressing Sig1R had an earlier recurrence and worse overall survival than those not overexpressing Sig1R. Cox regression analysis revealed that Sig1R was an independent factor to predict HC recurrence and prognosis of HC patients. Our results suggest that Sig1R is frequently activated in human HC tissue and overexpression of Sig1R might serve as a predictor for tumor recurrence and a prognostic biomarker for HC patients.","Source":"PubMed","category":"HUMAN","training_data":"Overexpression of Sig1R is closely associated with tumor progression and poor outcome in patients with hilar cholangiocarcinoma Nonopioid Sigma1 receptor (Sig1R), which regulates various metabolism functions, has been implicated in cancers; yet, its role in hilar cholangiocarcinoma remains unclear. In the present study, we examined Sig1R expression in hilar cholangiocarcinoma (HC) tissues and explored its possible clinical values. Tissue microarray blocks containing 92 HC tissues and matched non-cancerous bile duct tissues were examined immunohistochemically for expression of Sig1R protein. Overexpression of Sig1R was found in 43 (46.7%) of the 92 primary tumor tissues. Overexpression of Sig1R was significantly associated with poor/undifferentiation (P = 0.011), tumor invasion (P = 0.001), lymph node metastasis (P = 0.047), and advanced disease stage (P = 0.024) of HC patients. Kaplan-Meier analysis showed that patients overexpressing Sig1R had an earlier recurrence and worse overall survival than those not overexpressing Sig1R. Cox regression analysis revealed that Sig1R was an independent factor to predict HC recurrence and prognosis of HC patients. Our results suggest that Sig1R is frequently activated in human HC tissue and overexpression of Sig1R might serve as a predictor for tumor recurrence and a prognostic biomarker for HC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison blumgart anastomosis method traditional ductomucosal method result post pancreaticoduodenectomy reconstruction introduction important factor responsible morbidity mortality peri ampullary site tumor surgery leakage pancreatic anastomosis recent studies show approximately 10 leakage rate several alternative surgical techniques developed still developing reduce aim study compare postoperative results ba technique traditional ducto mucosal dm anastomosis method 73 patients went pancreaticoduedenectomy surgery april 2008 august 2013 pancreaticojejunostomy carried via ba technique 38 patients traditional dm anastomosis technique performed 35 patients age gender anastomosis leak type leak pathologic diagnosis morbidity mortality duration stay hospital inspected retrospectively pancreatic anastomosis leakage resulting complications mortality compared results primary diagnosis age gender features groups similar pancreatic leakage ba dm group observed 10 5 31 respectively p 0 05 three patients grade 1 patient grade b stula ba group four patients grade seven patients grade b stulas dm group p 0 05 neither groups patients grade c stula general complications rate 27 8 ba 48 5 dm group p 0 05 perioperative mortality observed one patient ba group three patients dm group causes mortality determined thromboembolism myocardial infarction mean time discharge 8 15 days ba group respectively p 0 05 conclusions blumgart anastomosis performed safe method used post pancreaticoduodenectomy reconstruction terms reduction pancreatic anastomosis leakage complications associated stulas google scholar","probabilities":0.9799733,"Title":"The Comparison Of Blumgart Anastomosis Method With Traditional Ductomucosal Method Result In Post Pancreaticoduodenectomy Reconstruction","Abstract":"Introduction: The most important factor that responsible for morbidity and mortality in peri-ampullary site tumor surgery is leakage in pancreatic anastomosis. Recent studies show an approximately 10% leakage rate in which several alternative surgical techniques have been developed and still being developing to reduce it. The aim of this study is to compare the postoperative results of BA technique with traditional ducto-mucosal (DM) anastomosis. Method: 73 patients went under pancreaticoduedenectomy surgery between April 2008 and August 2013. Pancreaticojejunostomy was carried out via BA technique in 38 patients and traditional DM anastomosis technique was performed in 35 patients. Age, gender, anastomosis leak, type of leak, pathologic diagnosis, morbidity, mortality and duration of stay in hospital were inspected retrospectively. The pancreatic anastomosis leakage and the resulting complications and mortality were compared. Results: The primary diagnosis, age and gender features in both groups were similar. Pancreatic leakage in BA and DM group were observed to be 10.5% and 31%, respectively (p < 0.05). Three patients had grade A, 1 patient had grade B fistula and in BA group. Four patients had grade A, seven patients had grade B fistulas in DM group (p > 0.05). Neither of the groups had patients with grade C fistula. General complications rate were 27.8% in BA, and 48.5% in DM group (p < 0.05). Perioperative mortality was observed in one patient in BA group and three patients in DM group. The causes of mortality were determined as thromboembolism and myocardial infarction. The mean time of discharge were 8 and 15 days in BA and the other group, respectively (p < 0.05). Conclusions: Blumgart anastomosis can be performed to be a safe method to be used in post pancreaticoduodenectomy reconstruction in terms of reduction in pancreatic anastomosis leakage and complications associated with fistulas.","Source":"Google Scholar","category":"HUMAN","training_data":"The Comparison Of Blumgart Anastomosis Method With Traditional Ductomucosal Method Result In Post Pancreaticoduodenectomy Reconstruction Introduction: The most important factor that responsible for morbidity and mortality in peri-ampullary site tumor surgery is leakage in pancreatic anastomosis. Recent studies show an approximately 10% leakage rate in which several alternative surgical techniques have been developed and still being developing to reduce it. The aim of this study is to compare the postoperative results of BA technique with traditional ducto-mucosal (DM) anastomosis. Method: 73 patients went under pancreaticoduedenectomy surgery between April 2008 and August 2013. Pancreaticojejunostomy was carried out via BA technique in 38 patients and traditional DM anastomosis technique was performed in 35 patients. Age, gender, anastomosis leak, type of leak, pathologic diagnosis, morbidity, mortality and duration of stay in hospital were inspected retrospectively. The pancreatic anastomosis leakage and the resulting complications and mortality were compared. Results: The primary diagnosis, age and gender features in both groups were similar. Pancreatic leakage in BA and DM group were observed to be 10.5% and 31%, respectively (p < 0.05). Three patients had grade A, 1 patient had grade B fistula and in BA group. Four patients had grade A, seven patients had grade B fistulas in DM group (p > 0.05). Neither of the groups had patients with grade C fistula. General complications rate were 27.8% in BA, and 48.5% in DM group (p < 0.05). Perioperative mortality was observed in one patient in BA group and three patients in DM group. The causes of mortality were determined as thromboembolism and myocardial infarction. The mean time of discharge were 8 and 15 days in BA and the other group, respectively (p < 0.05). Conclusions: Blumgart anastomosis can be performed to be a safe method to be used in post pancreaticoduodenectomy reconstruction in terms of reduction in pancreatic anastomosis leakage and complications associated with fistulas. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"descriptive epidemiology bile duct carcinoma osaka objective outbreak bile duct carcinoma reported among workers certain printing company osaka japan descriptive epidemiological study conducted descriptive studies bile duct carcinoma osaka methods based data osaka cancer registry incidence survival rate intrahepatic extrahepatic bile duct carcinomas gallbladder carcinomas hepatocellular carcinomas analyzed study period 1975 2007 total 108 407 incidents retrieved osaka cancer registry age sex specific incidence rates age standardized incidence rates calculated standardized incidence ratios evaluated municipality osaka prefecture relative 5 year survival rates also calculated cases diagnosed 1993 2005 results age standardized incidence rates bile duct carcinomas increased distinctly middle 1970s early 1980s males 1990s females however distinct increase incidence rates observed 2000 standardized incidence ratios exceed unity significantly males 1992 2007 females standardized incidence ratios exceeded unity significantly regions without relation location printing company outbreak reported relative 5 year survival rate generally poor however patients diagnosed localized disease age 25 49 years showed better survival conclusion neither change trend regional accumulation bile duct carcinoma confirmed osaka corresponding outbreak reported printing company pubmed","probabilities":0.9799733,"Title":"Descriptive epidemiology of bile duct carcinoma in Osaka","Abstract":"OBJECTIVE: An outbreak of bile duct carcinoma has been reported among workers in a certain printing company in Osaka, Japan, where there was no descriptive epidemiological study. We conducted descriptive studies of bile duct carcinoma in Osaka. METHODS: Based on the data from the Osaka Cancer Registry, the incidence and survival rate of intrahepatic and extrahepatic bile duct carcinomas, gallbladder carcinomas and hepatocellular carcinomas were analyzed. The study period was between 1975 and 2007, and total 108 407 incidents were retrieved from the Osaka Cancer Registry. Age- and sex-specific incidence rates and age-standardized incidence rates were calculated. Standardized incidence ratios were evaluated for each municipality in Osaka prefecture. Relative 5-year survival rates were also calculated for the cases diagnosed between 1993 and 2005. RESULTS: Age-standardized incidence rates of bile duct carcinomas increased distinctly from the middle of the 1970s to the early 1980s in males and the 1990s in females. However, no distinct increase in the incidence rates was observed in 2000. Standardized incidence ratios of those did not exceed the unity significantly in males between 1992 and 2007. In females, standardized incidence ratios exceeded the unity significantly in a few regions without any relation to the location of the printing company where the outbreak was reported. The relative 5-year survival rate is generally poor; however, patients who were diagnosed with localized disease at the age of 25-49 years showed a better survival. CONCLUSION: Neither change in trend nor regional accumulation of bile duct carcinoma was confirmed in Osaka, corresponding to the outbreak reported in the printing company.","Source":"PubMed","category":"HUMAN","training_data":"Descriptive epidemiology of bile duct carcinoma in Osaka OBJECTIVE: An outbreak of bile duct carcinoma has been reported among workers in a certain printing company in Osaka, Japan, where there was no descriptive epidemiological study. We conducted descriptive studies of bile duct carcinoma in Osaka. METHODS: Based on the data from the Osaka Cancer Registry, the incidence and survival rate of intrahepatic and extrahepatic bile duct carcinomas, gallbladder carcinomas and hepatocellular carcinomas were analyzed. The study period was between 1975 and 2007, and total 108 407 incidents were retrieved from the Osaka Cancer Registry. Age- and sex-specific incidence rates and age-standardized incidence rates were calculated. Standardized incidence ratios were evaluated for each municipality in Osaka prefecture. Relative 5-year survival rates were also calculated for the cases diagnosed between 1993 and 2005. RESULTS: Age-standardized incidence rates of bile duct carcinomas increased distinctly from the middle of the 1970s to the early 1980s in males and the 1990s in females. However, no distinct increase in the incidence rates was observed in 2000. Standardized incidence ratios of those did not exceed the unity significantly in males between 1992 and 2007. In females, standardized incidence ratios exceeded the unity significantly in a few regions without any relation to the location of the printing company where the outbreak was reported. The relative 5-year survival rate is generally poor; however, patients who were diagnosed with localized disease at the age of 25-49 years showed a better survival. CONCLUSION: Neither change in trend nor regional accumulation of bile duct carcinoma was confirmed in Osaka, corresponding to the outbreak reported in the printing company. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expert consensus document cholangiocarcinoma current knowledge future perspectives consensus statement european network study cholangiocarcinoma ens cca cholangiocarcinoma cca heterogeneous group malignancies features biliary tract differentiation cca second common primary liver tumour incidence increasing worldwide cca high mortality owing aggressiveness late diagnosis refractory nature may 2015 european network study cholangiocarcinoma ens cca www enscca org www cholangiocarcinoma eu created promote boost international research collaboration study cca basic translational clinical level consensus statement aim provide valuable information classifications pathological features risk factors cells origin genetic epigenetic modifications current therapies available cancer moreover future directions basic clinical investigations plans ens cca highlighted pubmed","probabilities":0.9799733,"Title":"Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA)","Abstract":"Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the \"European Network for the Study of Cholangiocarcinoma\" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted.","Source":"PubMed","category":"HUMAN","training_data":"Expert consensus document: Cholangiocarcinoma: current knowledge and future perspectives consensus statement from the European Network for the Study of Cholangiocarcinoma (ENS-CCA) Cholangiocarcinoma (CCA) is a heterogeneous group of malignancies with features of biliary tract differentiation. CCA is the second most common primary liver tumour and the incidence is increasing worldwide. CCA has high mortality owing to its aggressiveness, late diagnosis and refractory nature. In May 2015, the \"European Network for the Study of Cholangiocarcinoma\" (ENS-CCA: www.enscca.org or www.cholangiocarcinoma.eu) was created to promote and boost international research collaboration on the study of CCA at basic, translational and clinical level. In this Consensus Statement, we aim to provide valuable information on classifications, pathological features, risk factors, cells of origin, genetic and epigenetic modifications and current therapies available for this cancer. Moreover, future directions on basic and clinical investigations and plans for the ENS-CCA are highlighted. PubMed","prediction_labels":"HUMAN"},{"cleaned":"proximal margin resected hilar cholangiocarcinoma effect microscopic positive margin long term survival achieving r0 resection difficult hilar cholangiocarcinoma hc anatomic structures hepatic hilum frequent tumor infiltration aim study evaluate margin status bile duct resected hc prognostic impact r1 resection 2000 2009 245 patients underwent operation hc asan medical center retrospectively analyzed clinicopathologic features surgical outcomes focusing proximal margin status 162 cases patients curative intention curative resections achieved 125 52 1 patients r1 resections performed 43 26 5 proximal ductal margin states classified free margin 73 5 carcinoma situ 3 7 invasive carcinoma 22 8 3 5 year survival rates r1 group 39 5 34 9 significantly different rates r0 group 55 5 44 5 respectively multivariate analysis showed lymph node metastasis p 0 001 histologic differentiation p 0 001 independent predictors patient survival aggressive surgical approach based liver resection including caudate lobe may increase number patients eligible curative chance improve long term survival even microscopically positive margin still achieved pubmed","probabilities":0.9799733,"Title":"The proximal margin of resected hilar cholangiocarcinoma: the effect of microscopic positive margin on long-term survival","Abstract":"Achieving an R0 resection can be difficult for hilar cholangiocarcinoma (HC) because of the anatomic structures of the hepatic hilum and frequent tumor infiltration. The aim of this study was to evaluate the margin status of bile duct resected in HC and prognostic impact of R1 resection. Between 2000 and 2009, 245 patients underwent operation for HC at Asan Medical Center. We retrospectively analyzed the clinicopathologic features and surgical outcomes, focusing on the proximal margin status, of 162 cases of patients with curative intention. Curative resections were achieved in 125 (52.1%) patients, and R1 resections were performed in 43 (26.5%). Proximal ductal margin states were classified as free margin (73.5%), carcinoma in situ (3.7%), and invasive carcinoma (22.8%). The 3- and 5-year survival rates of the R1 group (39.5% and 34.9%) were not significantly different from the rates of the R0 group (55.5% and 44.5%, respectively). Multivariate analysis showed lymph node metastasis (P = 0.001) and histologic differentiation (P = 0.001) were independent predictors of patient survival. The aggressive surgical approach based on liver resection including caudate lobe may increase the number of patients eligible for a curative chance and improve long-term survival even if the microscopically positive margin is still achieved.","Source":"PubMed","category":"HUMAN","training_data":"The proximal margin of resected hilar cholangiocarcinoma: the effect of microscopic positive margin on long-term survival Achieving an R0 resection can be difficult for hilar cholangiocarcinoma (HC) because of the anatomic structures of the hepatic hilum and frequent tumor infiltration. The aim of this study was to evaluate the margin status of bile duct resected in HC and prognostic impact of R1 resection. Between 2000 and 2009, 245 patients underwent operation for HC at Asan Medical Center. We retrospectively analyzed the clinicopathologic features and surgical outcomes, focusing on the proximal margin status, of 162 cases of patients with curative intention. Curative resections were achieved in 125 (52.1%) patients, and R1 resections were performed in 43 (26.5%). Proximal ductal margin states were classified as free margin (73.5%), carcinoma in situ (3.7%), and invasive carcinoma (22.8%). The 3- and 5-year survival rates of the R1 group (39.5% and 34.9%) were not significantly different from the rates of the R0 group (55.5% and 44.5%, respectively). Multivariate analysis showed lymph node metastasis (P = 0.001) and histologic differentiation (P = 0.001) were independent predictors of patient survival. The aggressive surgical approach based on liver resection including caudate lobe may increase the number of patients eligible for a curative chance and improve long-term survival even if the microscopically positive margin is still achieved. PubMed","prediction_labels":"HUMAN"},{"cleaned":"dna pkcs ku70 predictive markers poor prognosis patients gall bladder malignancies gall bladder cancers gbcs highly resistant radiotherapy chemotherapy unfortunately key molecular mechanisms responsible therapeutic resistance identified study expression dna pkcs ku70 46 squamous cell adenosquamous carcinomas sc ascs 80 adenocarcinomas acs examined immunohistochemical analysis positive dna pkcs ku70 expression significantly associated less lymph node metastasis invasion low tnm stage sc ascs acs univariate kaplan meier analysis showed loss dna pkcs ku70 expression significantly correlated decreased survival sc asc ac patients multivariate cox regression analysis showed loss dna pkcs ku70 expression independent poor prognostic predictor sc asc ac patients study suggested dna pkcs ku70 tumor suppressors loss dna pkcs ku70 expression important biological marker metastasis invasion prognosis gbc currently implication dna pkcs ku70 expression chemoresistance radioresistance gbc stn","probabilities":0.9467213,"Title":"Dna-Pkcs And Ku70 Are Predictive Markers For Poor Prognosis Of Patients With Gall Bladder Malignancies","Abstract":"Gall bladder cancers (GBCs) are highly resistant to radiotherapy and chemotherapy. Unfortunately, the key molecular mechanisms responsible for therapeutic resistance have not been identified. In this study, the expression of DNA-PKcs and Ku70 in 46 squamous cell/adenosquamous carcinomas (SC/ASCs) and 80 adenocarcinomas (ACs) were examined by immunohistochemical analysis. Positive DNA-PKcs and Ku70 expression were significantly associated with less lymph node metastasis, invasion, and low TNM stage of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that loss of DNA-PKcs and Ku70 expression significantly correlated with decreased survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that loss of DNA-PKcs and Ku70 expression was an independent poor prognostic predictor in both SC/ASC and AC patients. Our study suggested that DNA-PKcs and Ku70 are tumor suppressors, and loss of DNA-PKcs and Ku70 expression is an important biological marker for metastasis, invasion, and prognosis of GBC. Currently, there is no implication of DNA-PKcs and Ku70 expression in chemoresistance or radioresistance in GBC.","Source":"STN","category":"HUMAN","training_data":"Dna-Pkcs And Ku70 Are Predictive Markers For Poor Prognosis Of Patients With Gall Bladder Malignancies Gall bladder cancers (GBCs) are highly resistant to radiotherapy and chemotherapy. Unfortunately, the key molecular mechanisms responsible for therapeutic resistance have not been identified. In this study, the expression of DNA-PKcs and Ku70 in 46 squamous cell/adenosquamous carcinomas (SC/ASCs) and 80 adenocarcinomas (ACs) were examined by immunohistochemical analysis. Positive DNA-PKcs and Ku70 expression were significantly associated with less lymph node metastasis, invasion, and low TNM stage of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that loss of DNA-PKcs and Ku70 expression significantly correlated with decreased survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that loss of DNA-PKcs and Ku70 expression was an independent poor prognostic predictor in both SC/ASC and AC patients. Our study suggested that DNA-PKcs and Ku70 are tumor suppressors, and loss of DNA-PKcs and Ku70 expression is an important biological marker for metastasis, invasion, and prognosis of GBC. Currently, there is no implication of DNA-PKcs and Ku70 expression in chemoresistance or radioresistance in GBC. STN","prediction_labels":"ANIMAL"},{"cleaned":"bioactive constituents isolated atractylodes lancea thunb dc background cholangiocarcinoma cca primary type bile duct cancer high morbidity mortality particularly patients advanced stage disease treatment cca remains unsatisfactory due lack sensitive specific diagnostic tool early detection well effective chemotherapeutics purpose investigate cytotoxic interactions three major constituents rhizomes atractylodes lancea thunb dc ie eudesmol atractylodin hinesol hs cca cell line methods cytotoxic activities human cca cells cl 6 dual hs hs triple hs combinations evaluated using mtt assay cytotoxic interaction dual combination assessed five concentration ratios 10 0 7 3 5 5 3 7 0 10 using isobologram analysis triple combination concentration ratio used experiment 1 1 5 2 5 hs analysis interaction performed using polygonogram analysis concentrations inhibit cell growth 50 90 respectively results combination produced additive effect sum fractional inhibitory concentration 0 967 0 02 mean sd hs hs combinations produced synergistic effect sum fractional inhibitory concentrations 0 685 0 08 0 767 0 09 respectively mixture three compounds produced synergistic interaction combination index values 0 519 0 10 0 65 0 17 mean sd concentrations inhibit cell growth 50 90 leveled respectively conclusion results obtained guide development atractylodes lancea thunb dc potential anti cca chemotherapeutics concerning appropriate pharmaceutical dosage form stn","probabilities":0.9467213,"Title":"Bioactive Constituents Isolated From Atractylodes Lancea (Thunb) Dc","Abstract":"Background: Cholangiocarcinoma (CCA) is the primary type of bile duct cancer with high morbidity and mortality, particularly in patients with advanced-stage disease. Treatment of CCA remains unsatisfactory due to the lack of sensitive and specific diagnostic tool for early detection as well as effective chemotherapeutics. \r\n\r\n Purpose: To investigate cytotoxic interactions between the three major constituents of the rhizomes of Atractylodes lancea (Thunb.) DC., ie, β-eudesmol (BE), atractylodin (AT), and hinesol (HS), against CCA cell line. \r\n\r\n Methods: Cytotoxic activities against the human CCA cells CL-6 of the dual (BE:AT, BE:HS, and AT:HS) and triple (BE:AT:HS) combinations were evaluated using MTT assay. The cytotoxic interaction of each dual combination was assessed at five concentration ratios (10:0, 7:3, 5:5, 3:7, and 0:10) using isobologram analysis. For triple combination, the concentration ratio used in the experiment was 1:1.5:2.5 (BE:AT:HS) and analysis of the interaction was performed using polygonogram analysis at the concentrations that inhibit cell growth by 50% and 90%, respectively. \r\n\r\n Results: The BE:AT combination produced the additive effect with sum fractional inhibitory concentration of 0.967±0.02 (mean ± SD). The BE:HS and AT:HS combinations produced a synergistic effect with sum fractional inhibitory concentrations of 0.685±0.08 and 0.767±0.09, respectively. The mixture of the three compounds produced synergistic interaction with combination index values of 0.519±0.10 and 0.65±0.17 (mean ± SD) at the concentrations that inhibit cell growth at the 50% and 90% leveled, respectively. \r\n\r\n Conclusion: Results obtained would guide further development of Atractylodes lancea (Thunb.) DC. as potential anti-CCA chemotherapeutics concerning the appropriate pharmaceutical dosage form.","Source":"STN","category":"ANIMAL","training_data":"Bioactive Constituents Isolated From Atractylodes Lancea (Thunb) Dc Background: Cholangiocarcinoma (CCA) is the primary type of bile duct cancer with high morbidity and mortality, particularly in patients with advanced-stage disease. Treatment of CCA remains unsatisfactory due to the lack of sensitive and specific diagnostic tool for early detection as well as effective chemotherapeutics. \r\n\r\n Purpose: To investigate cytotoxic interactions between the three major constituents of the rhizomes of Atractylodes lancea (Thunb.) DC., ie, β-eudesmol (BE), atractylodin (AT), and hinesol (HS), against CCA cell line. \r\n\r\n Methods: Cytotoxic activities against the human CCA cells CL-6 of the dual (BE:AT, BE:HS, and AT:HS) and triple (BE:AT:HS) combinations were evaluated using MTT assay. The cytotoxic interaction of each dual combination was assessed at five concentration ratios (10:0, 7:3, 5:5, 3:7, and 0:10) using isobologram analysis. For triple combination, the concentration ratio used in the experiment was 1:1.5:2.5 (BE:AT:HS) and analysis of the interaction was performed using polygonogram analysis at the concentrations that inhibit cell growth by 50% and 90%, respectively. \r\n\r\n Results: The BE:AT combination produced the additive effect with sum fractional inhibitory concentration of 0.967±0.02 (mean ± SD). The BE:HS and AT:HS combinations produced a synergistic effect with sum fractional inhibitory concentrations of 0.685±0.08 and 0.767±0.09, respectively. The mixture of the three compounds produced synergistic interaction with combination index values of 0.519±0.10 and 0.65±0.17 (mean ± SD) at the concentrations that inhibit cell growth at the 50% and 90% leveled, respectively. \r\n\r\n Conclusion: Results obtained would guide further development of Atractylodes lancea (Thunb.) DC. as potential anti-CCA chemotherapeutics concerning the appropriate pharmaceutical dosage form. STN","prediction_labels":"ANIMAL"},{"cleaned":"new prognostic scoring system using factors available preoperatively predict survival operative resection perihilar cholangiocarcinoma background perihilar cholangiocarcinoma one poorest prognoses cancers however mortality morbidity rates surgical resection 0 15 14 66 respectively additionally 5 year overall survival rates reported 22 40 findings indicate selected patients achieve satisfactory beneficial effects operative treatment retrospective study sought investigate preoperatively available prognostic factors establish new preoperative staging system predict survival major hepatectomy perihilar cholangiocarcinoma patients methods evaluated 121 consecutive patients underwent operative exploration perihilar cholangiocarcinoma results univariate multivariate analysis using identified preoperative factors revealed 4 factors platelet lymphocyte ratio plr 150 serum c reactive protein crp levels 0 5 mg dl albumin levels 3 5 g dl carcinoembryonic antigen cea levels 7 0 ng ml independent prognostic factors postoperative survival 4 preoperative factors allocated 1 point total score defined preoperative prognostic score pps patients pps 0 1 2 3 4 5 year survival 84 3 51 3 46 4 0 respectively also differences 5 year survival according pps 0 vs 1 p 013 2 vs 3 4 p 001 patients total pps 3 4 dismal prognosis median survival 11 3 months conclusion new preoperative scoring system using plr serum crp albumin cea levels predict postoperative survival resection perihilar cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"A new prognostic scoring system using factors available preoperatively to predict survival after operative resection of perihilar cholangiocarcinoma","Abstract":"BACKGROUND: Perihilar cholangiocarcinoma has one of the poorest prognoses of all cancers. However, mortality and morbidity rates after surgical resection are 0-15% and 14-66%, respectively. Additionally, the 5-year overall survival rates are reported at 22-40%. These findings indicate that only selected patients achieve satisfactory beneficial effects from operative treatment. This retrospective study sought to investigate preoperatively available prognostic factors and establish a new preoperative staging system to predict survival after major hepatectomy of perihilar cholangiocarcinoma. PATIENTS AND METHODS: We evaluated 121 consecutive patients who underwent operative exploration for perihilar cholangiocarcinoma. RESULTS: Univariate and multivariate analysis using the identified preoperative factors revealed that 4 factors (platelet-lymphocyte ratio [PLR] > 150, serum C-reactive protein [CRP] levels > 0.5 mg/dL, albumin levels < 3.5 g/dL, and carcinoembryonic antigen [CEA] levels > 7.0 ng/mL) were independent prognostic factors of postoperative survival. These 4 preoperative factors were allocated 1 point each. The total score was defined as the Preoperative Prognostic Score (PPS). Patients with a PPS of 0, 1, 2, or 3/4 had a 5-year survival of 84.3%, 51.3%, 46.4%, and 0%, respectively. There were also differences in the 5-year survival according to the PPS (0 vs 1 [P = .013] and 2 vs 3/4 [P < .001]). Patients with a total PPS of 3/4 had a dismal prognosis, with a median survival of 11.3 months. CONCLUSION: A new preoperative scoring system using PLR, serum CRP, albumin, and CEA levels could predict postoperative survival resection of perihilar cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"A new prognostic scoring system using factors available preoperatively to predict survival after operative resection of perihilar cholangiocarcinoma BACKGROUND: Perihilar cholangiocarcinoma has one of the poorest prognoses of all cancers. However, mortality and morbidity rates after surgical resection are 0-15% and 14-66%, respectively. Additionally, the 5-year overall survival rates are reported at 22-40%. These findings indicate that only selected patients achieve satisfactory beneficial effects from operative treatment. This retrospective study sought to investigate preoperatively available prognostic factors and establish a new preoperative staging system to predict survival after major hepatectomy of perihilar cholangiocarcinoma. PATIENTS AND METHODS: We evaluated 121 consecutive patients who underwent operative exploration for perihilar cholangiocarcinoma. RESULTS: Univariate and multivariate analysis using the identified preoperative factors revealed that 4 factors (platelet-lymphocyte ratio [PLR] > 150, serum C-reactive protein [CRP] levels > 0.5 mg/dL, albumin levels < 3.5 g/dL, and carcinoembryonic antigen [CEA] levels > 7.0 ng/mL) were independent prognostic factors of postoperative survival. These 4 preoperative factors were allocated 1 point each. The total score was defined as the Preoperative Prognostic Score (PPS). Patients with a PPS of 0, 1, 2, or 3/4 had a 5-year survival of 84.3%, 51.3%, 46.4%, and 0%, respectively. There were also differences in the 5-year survival according to the PPS (0 vs 1 [P = .013] and 2 vs 3/4 [P < .001]). Patients with a total PPS of 3/4 had a dismal prognosis, with a median survival of 11.3 months. CONCLUSION: A new preoperative scoring system using PLR, serum CRP, albumin, and CEA levels could predict postoperative survival resection of perihilar cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence comparative outcomes periampullary cancer population based analysis demonstrating improved outcomes increased use adjuvant therapy 2004 2012 background objectives periampullary adenocarcinoma pac stratified anatomically ampullary adenocarcinoma aa distal cholangiocarcinoma dcc duodenal adenocarcinoma da pancreatic ductal adenocarcinoma pdac aimed determine differences incidence prognosis treatment stage matched pac patients longitudinal study methods pac patients identified national cancer database 2004 2012 clinicopathological variables compared subtypes covariate adjusted treatment use os compared results 116 705 patients pac identified 1320 9 aa 3732 3 dcc 7142 6 da 95 511 82 pdac da dcc pdac associated worse survival compared aa hazard ratio hr 1 10 95 ci 1 1 1 1 hr 1 50 95 ci 1 4 1 6 hr 1 90 95 ci 1 8 1 9 among resected patients da associated improved survival compared aa hr 0 70 95 ci 0 67 0 75 dcc pdac associated worse survival hr 1 41 95 ci 1 31 1 53 hr 2 041 95 ci 1 07 2 12 resected aa pdac da dcc demonstrated significantly improved survival studied period patients increased adjuvant therapy receipt time p 0 001 patients pdac increased neoadjuvant therapy nat receipt p 0 001 conclusion resected pdac aa da associated clinically significant improved survival time mirroring concurrent associated increased receipt pubmed","probabilities":0.9799733,"Title":"Incidence and comparative outcomes of periampullary cancer: A population-based analysis demonstrating improved outcomes and increased use of adjuvant therapy from 2004 to 2012","Abstract":"BACKGROUND AND OBJECTIVES: Periampullary adenocarcinoma (PAC) is stratified anatomically: ampullary adenocarcinoma (AA), distal cholangiocarcinoma (DCC), duodenal adenocarcinoma (DA), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine differences in incidence, prognosis, and treatment in stage-matched PAC patients in a longitudinal study. METHODS: PAC patients were identified in The National Cancer Database from 2004 to 2012. Clinicopathological variables were compared between subtypes. Covariate-adjusted treatment use and OS were compared. RESULTS: The 116 705 patients with PAC were identified: 1320 (9%) AA, 3732 (3%) DCC, 7142 (6%) DA, and 95 511 (82%) PDAC. DA, DCC, and PDAC were associated with worse survival compared with AA (hazard ratio [HR], 1.10; 95% CI, 1.1-1.1; HR, 1.50; 95% CI, 1.4-1.6, and HR, 1.90; 95% CI, 1.8-1.9). Among resected patients, DA was associated with improved survival compared with AA (HR, 0.70; 95% CI, 0.67-0.75); DCC and PDAC were associated with worse survival (HR, 1.41; 95% CI, 1.31-1.53 and HR, 2.041; 95% CI, 1.07-2.12). Resected AA, PDAC, and DA, but not DCC, demonstrated significantly improved survival over the studied period. While all patients had increased adjuvant therapy (AT) receipt over time (P < 0.001), only patients with PDAC had increased neoadjuvant therapy (NAT) receipt ( P < 0.001). CONCLUSION: Resected PDAC, AA, and DA were associated with clinically significant improved survival over time, mirroring a concurrent associated increased receipt of AT.","Source":"PubMed","category":"HUMAN","training_data":"Incidence and comparative outcomes of periampullary cancer: A population-based analysis demonstrating improved outcomes and increased use of adjuvant therapy from 2004 to 2012 BACKGROUND AND OBJECTIVES: Periampullary adenocarcinoma (PAC) is stratified anatomically: ampullary adenocarcinoma (AA), distal cholangiocarcinoma (DCC), duodenal adenocarcinoma (DA), and pancreatic ductal adenocarcinoma (PDAC). We aimed to determine differences in incidence, prognosis, and treatment in stage-matched PAC patients in a longitudinal study. METHODS: PAC patients were identified in The National Cancer Database from 2004 to 2012. Clinicopathological variables were compared between subtypes. Covariate-adjusted treatment use and OS were compared. RESULTS: The 116 705 patients with PAC were identified: 1320 (9%) AA, 3732 (3%) DCC, 7142 (6%) DA, and 95 511 (82%) PDAC. DA, DCC, and PDAC were associated with worse survival compared with AA (hazard ratio [HR], 1.10; 95% CI, 1.1-1.1; HR, 1.50; 95% CI, 1.4-1.6, and HR, 1.90; 95% CI, 1.8-1.9). Among resected patients, DA was associated with improved survival compared with AA (HR, 0.70; 95% CI, 0.67-0.75); DCC and PDAC were associated with worse survival (HR, 1.41; 95% CI, 1.31-1.53 and HR, 2.041; 95% CI, 1.07-2.12). Resected AA, PDAC, and DA, but not DCC, demonstrated significantly improved survival over the studied period. While all patients had increased adjuvant therapy (AT) receipt over time (P < 0.001), only patients with PDAC had increased neoadjuvant therapy (NAT) receipt ( P < 0.001). CONCLUSION: Resected PDAC, AA, and DA were associated with clinically significant improved survival over time, mirroring a concurrent associated increased receipt of AT. PubMed","prediction_labels":"HUMAN"},{"cleaned":"current insights cholangiocarcinoma research brief review colangiocarcinoma cca progressively fatal disease generally occurs due malignant transformation hepatic biliary cholangiocytes incidence cca increasing worldwide urgent requirement effective diagnosis treatment strategies devastating disease different factors including liver fluke infestation viral hepatitis exogenous nitrosamine mediated dna damage chronic inflammation linked cca genesis however risk factors underlying complex mechanisms leading development cca sufficiently understood devise effective targeted treatment therapy review summarize currently known epidemiological pathological aspects disease briefly describe various potential biomarkers experimental anticancer phytochemicals related cca research addition also sum recent findings link chronic inflammation hepatic biliary cholangiocytes cca collective information concisely presented article provide useful insights current understanding cancer pubmed","probabilities":0.9799733,"Title":"Current insights on cholangiocarcinoma research: a brief review","Abstract":"Colangiocarcinoma (CCA) is a progressively fatal disease which generally occurs due to malignant transformation of hepatic biliary cholangiocytes. The incidence of CCA has been increasing worldwide and there is an urgent requirement for effective diagnosis and treatment strategies against this devastating disease. Different factors including liver-fluke infestation, viral hepatitis, exogenous nitrosamine-mediated DNA damage, and chronic inflammation have been linked to CCA genesis. However, the risk factors and underlying complex mechanisms leading to development of CCA are not sufficiently understood to devise an effective targeted treatment therapy. In this review, we summarize currently known epidemiological and pathological aspects of the disease and briefly describe various potential biomarkers and experimental anticancer phytochemicals related to CCA research. In addition, we also sum up recent findings that link chronic inflammation of hepatic biliary cholangiocytes with CCA. The collective information concisely presented in this article would provide useful insights into the current understanding of this cancer.","Source":"PubMed","category":"HUMAN","training_data":"Current insights on cholangiocarcinoma research: a brief review Colangiocarcinoma (CCA) is a progressively fatal disease which generally occurs due to malignant transformation of hepatic biliary cholangiocytes. The incidence of CCA has been increasing worldwide and there is an urgent requirement for effective diagnosis and treatment strategies against this devastating disease. Different factors including liver-fluke infestation, viral hepatitis, exogenous nitrosamine-mediated DNA damage, and chronic inflammation have been linked to CCA genesis. However, the risk factors and underlying complex mechanisms leading to development of CCA are not sufficiently understood to devise an effective targeted treatment therapy. In this review, we summarize currently known epidemiological and pathological aspects of the disease and briefly describe various potential biomarkers and experimental anticancer phytochemicals related to CCA research. In addition, we also sum up recent findings that link chronic inflammation of hepatic biliary cholangiocytes with CCA. The collective information concisely presented in this article would provide useful insights into the current understanding of this cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"potential survival benefit radiofrequency ablation small solitary intrahepatic cholangiocarcinoma nonsurgically managed patients population based analysis background little data regarding selection nonsurgical therapies localized intrahepatic cholangiocarcinoma icc available methods cohort nonsurgically managed patients american joint commission cancer clinical stage ii icc united states 2004 2013 identified national cancer database overall survival os compared according treatment options radiofrequency ablation rfa vs chemoradiotherapy using propensity score matching results among 505 patients 86 patients treated rfa 419 patients treated chemoradiotherapy propensity matching n 84 group 5 year os 17 6 among patients underwent rfa vs 3 8 among patients receiving chemoradiotherapy p 001 bivariate analysis rfa related os benefit hazard ratio 0 46 95 confidence interval 0 33 0 66 p 001 specifially stage specific subgroup analysis revealed survival benefit favor rfa among stage patients 5 year os rfa 20 1 vs chemoradiotherapy 3 7 p 001 whereas difference os noted among patients stage ii disease conclusion among icc patients small 5 cm solitary icc without vascular invasion rfa associated better survival compared chemoradiotherapy pubmed","probabilities":0.9799733,"Title":"Potential survival benefit of radiofrequency ablation for small solitary intrahepatic cholangiocarcinoma in nonsurgically managed patients: A population-based analysis","Abstract":"BACKGROUND: Little data regarding the selection of nonsurgical therapies for localized intrahepatic cholangiocarcinoma (ICC) are available. METHODS: A cohort of nonsurgically managed patients with American Joint Commission on Cancer clinical stage I/II ICC in the United States from 2004 to 2013 were identified in the National Cancer Database. Overall survival (OS) was compared according to treatment options (radiofrequency ablation [RFA] vs chemoradiotherapy) using propensity-score matching. RESULTS: Among 505 patients, 86 patients were treated with RFA and 419 patients were treated with chemoradiotherapy. After propensity matching (n = 84, each group), 5-year OS was 17.6% among patients who underwent RFA vs 3.8% among patients receiving chemoradiotherapy (P < .001). On bivariate analysis, RFA was related to an OS benefit (hazard ratio, 0.46; 95% confidence interval, 0.33-0.66; P < .001). Specifially, a stage-specific subgroup analysis revealed a survival benefit in favor of RFA among stage I patients (5-year OS; RFA: 20.1% vs chemoradiotherapy: 3.7%, P < .001), whereas no difference in OS was noted among patients with stage II disease. CONCLUSION: Among ICC patients with small (≤5 cm), solitary ICC without vascular invasion, RFA was associated with better survival compared with chemoradiotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Potential survival benefit of radiofrequency ablation for small solitary intrahepatic cholangiocarcinoma in nonsurgically managed patients: A population-based analysis BACKGROUND: Little data regarding the selection of nonsurgical therapies for localized intrahepatic cholangiocarcinoma (ICC) are available. METHODS: A cohort of nonsurgically managed patients with American Joint Commission on Cancer clinical stage I/II ICC in the United States from 2004 to 2013 were identified in the National Cancer Database. Overall survival (OS) was compared according to treatment options (radiofrequency ablation [RFA] vs chemoradiotherapy) using propensity-score matching. RESULTS: Among 505 patients, 86 patients were treated with RFA and 419 patients were treated with chemoradiotherapy. After propensity matching (n = 84, each group), 5-year OS was 17.6% among patients who underwent RFA vs 3.8% among patients receiving chemoradiotherapy (P < .001). On bivariate analysis, RFA was related to an OS benefit (hazard ratio, 0.46; 95% confidence interval, 0.33-0.66; P < .001). Specifially, a stage-specific subgroup analysis revealed a survival benefit in favor of RFA among stage I patients (5-year OS; RFA: 20.1% vs chemoradiotherapy: 3.7%, P < .001), whereas no difference in OS was noted among patients with stage II disease. CONCLUSION: Among ICC patients with small (≤5 cm), solitary ICC without vascular invasion, RFA was associated with better survival compared with chemoradiotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"high monocyte lymphocyte ratio predicts poor prognosis patients advanced gallbladder cancer receiving chemotherapy background monocyte lymphocyte ratio mlr neutrophil lymphocyte ratio nlr platelet lymphocyte ratio plr reported prognostic markers various cancers however prognostic value inflammatory biomarkers particularly mlr gallbladder cancer remains determined methods 2005 2016 178 patients histologically confirmed gallbladder adenocarcinoma underwent palliative chemotherapy queried study association survival various clinical laboratory variables including mlr nlr plr investigated optimal cutoff values mlr nlr plr determined using maxstat package r results patients high mlr 0 24 expected shorter progression free survival pfs hazard ratio hr 2 100 95 confidence interval ci 1 397 3 157 p 0 001 overall survival os hr 2 533 95 ci 1 664 3 856 p 0 001 compared patients low mlr 0 24 multivariate cox model ca 19 9 stage mlr independent factors pfs mlr also independent predictor os along plr age ca 19 9 whereas nlr significantly associated os time dependent receiver operating characteristic roc analysis showed area curve mlr predicting os greater nlr plr time points conclusions mlr independently predicts survival gallbladder cancer patients undergoing chemotherapy future prospective studies needed validate value prognostic biomarker impact mlr inexpensive easily available biomarker predicting prognosis patients gallbladder cancer undergoing chemotherapy stn","probabilities":0.9799733,"Title":"A High Monocyte-To-Lymphocyte Ratio Predicts Poor Prognosis In Patients With Advanced Gallbladder Cancer Receiving Chemotherapy","Abstract":"Background: Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported to be prognostic markers in various cancers. However, the prognostic value of these inflammatory biomarkers, particularly MLR, in gallbladder cancer remains to be determined. \r\n\r\n Methods: From 2005 to 2016, 178 patients with histologically confirmed gallbladder adenocarcinoma who underwent palliative chemotherapy were queried in this study. The association between survival and various clinical and laboratory variables, including MLR, NLR, and PLR, was investigated. The optimal cutoff values for MLR, NLR, and PLR were determined using the maxstat package of R. \r\n\r\n Results: Patients with high MLR (>0.24) were expected to have shorter progression-free survival [PFS; hazard ratio (HR), 2.100; 95% confidence interval (CI), 1.397-3.157; P < 0.001] and overall survival (OS; HR, 2.533; 95% CI, 1.664-3.856; P < 0.001) compared with patients with low MLR (≤0.24). In multivariate Cox model, CA 19-9, stage, and MLR were independent factors for PFS. MLR was also an independent predictor of OS along with PLR, age, and CA 19-9, whereas NLR was not significantly associated with OS. Time-dependent receiver operating characteristic (ROC) analysis showed that the area under the curve of MLR for predicting OS was greater than that of NLR and PLR at most time points. \r\n\r\n Conclusions: MLR independently predicts survival in gallbladder cancer patients undergoing chemotherapy. Future prospective studies are needed to validate its value as a prognostic biomarker. \r\n\r\n Impact: MLR is an inexpensive and easily available biomarker for predicting prognosis in patients with gallbladder cancer undergoing chemotherapy.","Source":"STN","category":"HUMAN","training_data":"A High Monocyte-To-Lymphocyte Ratio Predicts Poor Prognosis In Patients With Advanced Gallbladder Cancer Receiving Chemotherapy Background: Monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) have been reported to be prognostic markers in various cancers. However, the prognostic value of these inflammatory biomarkers, particularly MLR, in gallbladder cancer remains to be determined. \r\n\r\n Methods: From 2005 to 2016, 178 patients with histologically confirmed gallbladder adenocarcinoma who underwent palliative chemotherapy were queried in this study. The association between survival and various clinical and laboratory variables, including MLR, NLR, and PLR, was investigated. The optimal cutoff values for MLR, NLR, and PLR were determined using the maxstat package of R. \r\n\r\n Results: Patients with high MLR (>0.24) were expected to have shorter progression-free survival [PFS; hazard ratio (HR), 2.100; 95% confidence interval (CI), 1.397-3.157; P < 0.001] and overall survival (OS; HR, 2.533; 95% CI, 1.664-3.856; P < 0.001) compared with patients with low MLR (≤0.24). In multivariate Cox model, CA 19-9, stage, and MLR were independent factors for PFS. MLR was also an independent predictor of OS along with PLR, age, and CA 19-9, whereas NLR was not significantly associated with OS. Time-dependent receiver operating characteristic (ROC) analysis showed that the area under the curve of MLR for predicting OS was greater than that of NLR and PLR at most time points. \r\n\r\n Conclusions: MLR independently predicts survival in gallbladder cancer patients undergoing chemotherapy. Future prospective studies are needed to validate its value as a prognostic biomarker. \r\n\r\n Impact: MLR is an inexpensive and easily available biomarker for predicting prognosis in patients with gallbladder cancer undergoing chemotherapy. STN","prediction_labels":"HUMAN"},{"cleaned":"combined photodynamic therapy systemic chemotherapy improves survival patients irresectable cholangiocarcinoma background chemotherapy gemcitabine cisplatin current standard patients unresectable cholangiocarcinoma local photodynamic therapy also demonstrated benefit patients extrahepatic cholangiocarcinoma aim evaluate benefit photodynamic therapy combination systemic chemotherapy advanced extrahepatic cholangiocarcinoma methods three hundred fifty three patients diagnosed cholangiocarcinoma 2004 2016 treated university hospital bonn germany 96 suffering unresectable extrahepatic cholangiocarcinoma included patients stratified according treatment combination photodynamic therapy chemotherapy 36 patients photodynamic therapy alone 34 patients chemotherapy alone 26 patients results combined photodynamic therapy chemotherapy resulted significantly longer overall survival chemotherapy alone p 0 022 median survival 20 months combination group 95 ci 16 38 23 62 15 months photodynamic alone group 95 ci 10 02 19 98 10 months chemotherapy alone group 95 ci 8 45 11 55 multivariate analysis combination therapy photodynamic therapy alone hr 0 41 95 ci 0 22 0 77 p 0 006 metal stenting radiofrequency ablation independent predictors longer survival conclusions combination photodynamic therapy chemotherapy well tolerated resulted significantly longer survival chemotherapy alone application photodynamic therapy significantly correlated longer survival demonstrating benefit advanced cholangiocarcinoma thus photodynamic therapy considered therapeutic decision making advanced cholangiocarcinoma google scholar","probabilities":0.9799733,"Title":"Combined Photodynamic Therapy With Systemic Chemotherapy Improves Survival Of Patients With Irresectable Cholangiocarcinoma","Abstract":"Background\nChemotherapy with gemcitabine and cisplatin is the current standard for patients with unresectable cholangiocarcinoma. Local photodynamic therapy has also demonstrated benefit in patients with extrahepatic cholangiocarcinoma.\nAim\nTo evaluate the benefit of photodynamic therapy in combination with systemic chemotherapy in advanced extrahepatic cholangiocarcinoma.\nMethods\nThree hundred and fifty‐three patients diagnosed with cholangiocarcinoma between 2004 and 2016 were treated at the University Hospital of Bonn, Germany. Of these, 96 suffering from unresectable extrahepatic cholangiocarcinoma were included. Patients were stratified according to treatment: combination photodynamic therapy and chemotherapy (36 patients), photodynamic therapy alone (34 patients), and chemotherapy alone (26 patients).\nResults\nCombined photodynamic therapy with chemotherapy resulted in significantly longer overall survival than chemotherapy alone (P = 0.022). Median survival was 20 months in the combination group (95% CI: 16.38‐23.62), 15 months in the photodynamic alone group (95% CI: 10.02‐19.98) and 10 months in the chemotherapy alone group (95% CI: 8.45‐11.55). In multivariate analysis, combination therapy and photodynamic therapy alone (HR: 0.41, 95% CI: 0.22‐0.77, P = 0.006), metal stenting, and radiofrequency ablation were independent predictors of longer survival. \nConclusions\nCombination photodynamic therapy and chemotherapy was well tolerated and resulted in significantly longer survival than chemotherapy alone. Application of photodynamic therapy significantly correlated with longer survival, demonstrating benefit in advanced cholangiocarcinoma. Thus, photodynamic therapy should be considered during therapeutic decision making in advanced cholangiocarcinoma.","Source":"Google Scholar","category":"HUMAN","training_data":"Combined Photodynamic Therapy With Systemic Chemotherapy Improves Survival Of Patients With Irresectable Cholangiocarcinoma Background\nChemotherapy with gemcitabine and cisplatin is the current standard for patients with unresectable cholangiocarcinoma. Local photodynamic therapy has also demonstrated benefit in patients with extrahepatic cholangiocarcinoma.\nAim\nTo evaluate the benefit of photodynamic therapy in combination with systemic chemotherapy in advanced extrahepatic cholangiocarcinoma.\nMethods\nThree hundred and fifty‐three patients diagnosed with cholangiocarcinoma between 2004 and 2016 were treated at the University Hospital of Bonn, Germany. Of these, 96 suffering from unresectable extrahepatic cholangiocarcinoma were included. Patients were stratified according to treatment: combination photodynamic therapy and chemotherapy (36 patients), photodynamic therapy alone (34 patients), and chemotherapy alone (26 patients).\nResults\nCombined photodynamic therapy with chemotherapy resulted in significantly longer overall survival than chemotherapy alone (P = 0.022). Median survival was 20 months in the combination group (95% CI: 16.38‐23.62), 15 months in the photodynamic alone group (95% CI: 10.02‐19.98) and 10 months in the chemotherapy alone group (95% CI: 8.45‐11.55). In multivariate analysis, combination therapy and photodynamic therapy alone (HR: 0.41, 95% CI: 0.22‐0.77, P = 0.006), metal stenting, and radiofrequency ablation were independent predictors of longer survival. \nConclusions\nCombination photodynamic therapy and chemotherapy was well tolerated and resulted in significantly longer survival than chemotherapy alone. Application of photodynamic therapy significantly correlated with longer survival, demonstrating benefit in advanced cholangiocarcinoma. Thus, photodynamic therapy should be considered during therapeutic decision making in advanced cholangiocarcinoma. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"factors affecting survival outcomes patients cholangiocarcinoma uk regional hepato biliary centre experience introduction incidence mortality intrahepatic bile duct cholangiocarcinoma cca risen worldwide past decades last four decades exponential rise age standardised mortality rate cca recorded england wales examined factors affecting survival cca regional hepato biliary centre method retrospectively reviewed 340 patients confirmed cca evaluate factors affecting survival period six years 2009 2014 hospital integrated data base used clinical radiological histological endoscopic details overall survival modality treatment examined kaplan meier log rank test factors contributing mortality assessed cox proportional hazards results female preponderance cca n 174 51 2 histology prevalent mode diagnosis n 154 45 3 palliative biliary stenting utilised treatment n 171 50 3 intrahepatic cca largest tumour diameter versus extrahepatic cca median 6 2 cm vs 3 0 cm p 0 0001 overall median survival 8 months range 7 11 median survival treated chemotherapy biliary stent best supportive care 16 11 18 5 4 6 4 2 7 months respectively 5 year survival post resection 80 surgical resection chemotherapy associated improved survival hr 0 13 95 ci 0 06 0 28 p 0 0001 hr 0 33 95 ci 0 17 0 60 p 0 0003 respectively whereas presence biliary calculi diagnosis conferred negative impact survival hr 1 83 95 ci 1 19 2 81 p 0 006 presence biliary calculi significant independent predictor survival patients hilar cca conclusion similar experience elsewhere observed surgical resection chemotherapy offered survival benefit cca patients association increased mortality presence biliary calculi prompts prospective investigation possibility diagnosis stone disease delays recognition coexisting bile duct tumours google scholar","probabilities":0.9799733,"Title":"Factors Affecting Survival Outcomes In Patients With Cholangiocarcinoma-A Uk Regional Hepato-Biliary Centre Experience","Abstract":"Introduction The incidence and mortality of Intrahepatic bile duct cholangiocarcinoma (CCA) has risen worldwide over the past few decades. Over the last four decades, an exponential rise in the age-standardised mortality rate of CCA has been recorded in England and Wales. We examined the factors affecting survival from CCA at a regional hepato-biliary centre.\nMethod We retrospectively reviewed 340 patients with confirmed CCA to evaluate the factors affecting survival over a period of six years (2009–2014). The hospital integrated data base was used for clinical, radiological, histological and endoscopic details. Overall survival by modality of treatment was examined by Kaplan-Meier log rank test. Factors contributing to mortality were assessed by Cox proportional hazards.\nResults There was a female preponderance of CCA (n = 174, 51.2%), histology being the most prevalent mode of diagnosis (n = 154, 45.3%) and palliative biliary stenting most utilised treatment (n = 171, 50.3%). Intrahepatic CCA had the largest tumour diameter versus extrahepatic CCA (median: 6.2 cm vs 3.0 cm, p= <0.0001). Overall median survival was 8 months (range 7–11). The median survival for those treated with chemotherapy, biliary stent and best supportive care were 16 (11–18), 5 (4–6) and 4 (2–7) months, respectively. 5 year survival post resection was 80%. Surgical resection and chemotherapy were associated with improved survival (HR: 0.13; 95% CI: 0.06–0.28, p < 0.0001) and (HR: 0.33; 95% CI: 0.17–0.60, p = 0.0003) respectively, whereas the presence of biliary calculi at diagnosis conferred a negative impact on survival (HR: 1.83; 95% CI: 1.19–2.81, p = 0.006). Presence of biliary calculi was a significant independent predictor of survival in patients with hilar CCA.\nConclusion Similar to experience elsewhere, we observed that surgical resection and chemotherapy offered survival benefit to CCA patients. The association of increased mortality in presence of biliary calculi prompts further prospective investigation of the possibility that the diagnosis of stone disease delays recognition of coexisting bile duct tumours.","Source":"Google Scholar","category":"HUMAN","training_data":"Factors Affecting Survival Outcomes In Patients With Cholangiocarcinoma-A Uk Regional Hepato-Biliary Centre Experience Introduction The incidence and mortality of Intrahepatic bile duct cholangiocarcinoma (CCA) has risen worldwide over the past few decades. Over the last four decades, an exponential rise in the age-standardised mortality rate of CCA has been recorded in England and Wales. We examined the factors affecting survival from CCA at a regional hepato-biliary centre.\nMethod We retrospectively reviewed 340 patients with confirmed CCA to evaluate the factors affecting survival over a period of six years (2009–2014). The hospital integrated data base was used for clinical, radiological, histological and endoscopic details. Overall survival by modality of treatment was examined by Kaplan-Meier log rank test. Factors contributing to mortality were assessed by Cox proportional hazards.\nResults There was a female preponderance of CCA (n = 174, 51.2%), histology being the most prevalent mode of diagnosis (n = 154, 45.3%) and palliative biliary stenting most utilised treatment (n = 171, 50.3%). Intrahepatic CCA had the largest tumour diameter versus extrahepatic CCA (median: 6.2 cm vs 3.0 cm, p= <0.0001). Overall median survival was 8 months (range 7–11). The median survival for those treated with chemotherapy, biliary stent and best supportive care were 16 (11–18), 5 (4–6) and 4 (2–7) months, respectively. 5 year survival post resection was 80%. Surgical resection and chemotherapy were associated with improved survival (HR: 0.13; 95% CI: 0.06–0.28, p < 0.0001) and (HR: 0.33; 95% CI: 0.17–0.60, p = 0.0003) respectively, whereas the presence of biliary calculi at diagnosis conferred a negative impact on survival (HR: 1.83; 95% CI: 1.19–2.81, p = 0.006). Presence of biliary calculi was a significant independent predictor of survival in patients with hilar CCA.\nConclusion Similar to experience elsewhere, we observed that surgical resection and chemotherapy offered survival benefit to CCA patients. The association of increased mortality in presence of biliary calculi prompts further prospective investigation of the possibility that the diagnosis of stone disease delays recognition of coexisting bile duct tumours. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"survival pathway cholangiocarcinoma via akt mtor signaling escape raf mek erk pathway inhibition sorafenib cholangiocarcinoma ccc strongly aggressive malignancy surgical resection potential curative therapy sorafenib multikinase inhibitor raf mek erk pathway molecular targeted drug approved hepatocellular carcinoma hcc ccc differences signaling pathway characteristics sorafenib treatment hcc hlf huh7 plc prf 5 ccc rbe ysccc huh28 cell lines therefore investigated using cell proliferation western blotting apoptosis analyses sorafenib inhibited cell growth significantly less ccc cells hcc cells lower suppression erk phosphorylation significantly decreased akt ser473 phosphorylation hcc cells conversely enhanced phosphorylation akt ser473 mtorc2 ccc cells observed sorafenib treatment disassembly mtorc2 complex rbe cells sirna targeting rictor resulted downregulation akt ser473 phosphorylation enhanced apoptosis presumably via increased foxo1 consequently suppressed rbe cell proliferation phosphorylation mtorc1 autophagy influenced sorafenib ccc cells simultaneous administration everolimus suppress activated mtorc1 rbe cells revealed combined everolimus sorafenib treatment mtorc2 disassembly enhance growth inhibition suppression sorafenib everolimus dependent akt ser473 phosphorylation addition inhibition mtorc1 phosphorylation prevention escape akt mtor signaling raf mek erk pathway sorafenib treatment suppressing mtorc2 activity may lead promising new approaches ccc therapy stn","probabilities":0.9467213,"Title":"Survival Pathway Of Cholangiocarcinoma Via Akt/Mtor Signaling To Escape Raf/Mek/Erk Pathway Inhibition By Sorafenib","Abstract":"Cholangiocarcinoma (CCC) is a strongly aggressive malignancy for which surgical resection is the only potential curative therapy. Sorafenib, a multikinase inhibitor of the RAF/MEK/ERK pathway, is a molecular-targeted drug that is approved for hepatocellular carcinoma (HCC) but not for CCC. The differences in signaling pathway characteristics under sorafenib treatment between HCC (HLF, Huh7, PLC/PRF/5) and CCC (RBE, YSCCC, Huh28) cell lines were therefore investigated using cell proliferation, western blotting, and apoptosis analyses. Sorafenib inhibited cell growth significantly less in CCC cells than in HCC cells, with lower suppression of ERK phosphorylation. Significantly decreased AKT Ser473 phosphorylation in HCC cells, and conversely enhanced phosphorylation of AKT Ser473 and mTORC2 in CCC cells, were observed with sorafenib treatment. Disassembly of the mTORC2 complex in RBE cells with siRNA targeting Rictor resulted in the downregulation of AKT Ser473 phosphorylation and enhanced apoptosis presumably via increased FOXO1, which consequently suppressed RBE cell proliferation. Phosphorylation of mTORC1 and autophagy were not influenced by sorafenib in CCC cells. Simultaneous administration of everolimus to suppress activated mTORC1 in RBE cells revealed that combined everolimus and sorafenib treatment under mTORC2 disassembly could enhance growth inhibition through the suppression of both sorafenib- and everolimus-dependent AKT Ser473 phosphorylation in addition to the inhibition of mTORC1 phosphorylation. Prevention of escape by AKT/mTOR signaling from the RAF/MEK/ERK pathway in sorafenib treatment by suppressing mTORC2 activity may lead to promising new approaches in CCC therapy.","Source":"STN","category":"ANIMAL","training_data":"Survival Pathway Of Cholangiocarcinoma Via Akt/Mtor Signaling To Escape Raf/Mek/Erk Pathway Inhibition By Sorafenib Cholangiocarcinoma (CCC) is a strongly aggressive malignancy for which surgical resection is the only potential curative therapy. Sorafenib, a multikinase inhibitor of the RAF/MEK/ERK pathway, is a molecular-targeted drug that is approved for hepatocellular carcinoma (HCC) but not for CCC. The differences in signaling pathway characteristics under sorafenib treatment between HCC (HLF, Huh7, PLC/PRF/5) and CCC (RBE, YSCCC, Huh28) cell lines were therefore investigated using cell proliferation, western blotting, and apoptosis analyses. Sorafenib inhibited cell growth significantly less in CCC cells than in HCC cells, with lower suppression of ERK phosphorylation. Significantly decreased AKT Ser473 phosphorylation in HCC cells, and conversely enhanced phosphorylation of AKT Ser473 and mTORC2 in CCC cells, were observed with sorafenib treatment. Disassembly of the mTORC2 complex in RBE cells with siRNA targeting Rictor resulted in the downregulation of AKT Ser473 phosphorylation and enhanced apoptosis presumably via increased FOXO1, which consequently suppressed RBE cell proliferation. Phosphorylation of mTORC1 and autophagy were not influenced by sorafenib in CCC cells. Simultaneous administration of everolimus to suppress activated mTORC1 in RBE cells revealed that combined everolimus and sorafenib treatment under mTORC2 disassembly could enhance growth inhibition through the suppression of both sorafenib- and everolimus-dependent AKT Ser473 phosphorylation in addition to the inhibition of mTORC1 phosphorylation. Prevention of escape by AKT/mTOR signaling from the RAF/MEK/ERK pathway in sorafenib treatment by suppressing mTORC2 activity may lead to promising new approaches in CCC therapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"regional chemotherapy unresectable intrahepatic cholangiocarcinoma potential role dynamic magnetic resonance imaging imaging biomarker survival update two prospective clinical trials background patients unresectable intrahepatic cholangiocarcinoma icc treatment options limited survival poor study summarizes long term outcome two previously reported clinical trials using hepatic arterial infusion hai floxuridine dexamethasone without bevacizumab advanced icc methods prospectively collected clinicopathologic survival data retrospectively reviewed response based response evaluation criteria solid tumors recist pre hai dynamic contrast enhanced magnetic resonance imaging dce mri images reviewed tumor perfusion data correlated outcome results forty four patients analyzed floxuridine 26 floxuridine bevacizumab 18 median follow 29 3 months 41 patients died disease partial response recist observed 48 50 stable disease three patients underwent resection response 82 received additional hai removal trials median survival similar trials floxuridine 29 3 months vs floxuridine bevacizumab 28 5 months p 0 96 ten 23 patients survived 3 years including 5 11 survived 5 years tumor perfusion measured pre treatment dce mri area gadolinium concentration curve 90 180 auc90 auc180 respectively significantly higher 3 year survivors factor distinguished group 3 year survivors mean auc90 22 6 vs 15 9 mm p 0 025 mean auc180 48 9 vs 32 3 mm p 0 003 respectively median hepatic progression free survival longer 3 year survivors 12 9 vs 9 3 months respectively p 0 008 conclusions hai chemotherapy result prolonged survival unresectable icc pre hai dce mri may predict treatment outcome google scholar","probabilities":0.9799733,"Title":"Regional Chemotherapy For Unresectable Intrahepatic Cholangiocarcinoma: A Potential Role For Dynamic Magnetic Resonance Imaging As An Imaging Biomarker And A Survival Update From Two Prospective Clinical Trials","Abstract":"Background\nFor patients with unresectable intrahepatic cholangiocarcinoma (ICC), treatment options are limited and survival is poor. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine and dexamethasone (with or without bevacizumab) in advanced ICC.\nMethods\nProspectively collected clinicopathologic and survival data were retrospectively reviewed. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion data correlated with outcome.\nResults\nForty-four patients were analyzed (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3 months, 41 patients had died of disease. Partial response by RECIST was observed in 48 %, and 50 % had stable disease. Three patients underwent resection after response, and 82 % received additional HAI after removal from the trials. Median survival was similar in both trials (floxuridine 29.3 months vs. floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived ≥3 years, including 5 (11 %) who survived ≥5 years. Tumor perfusion measured on pre-treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s (AUC90 and AUC180, respectively)] was significantly higher in ≥3-year survivors and was the only factor that distinguished this group from <3-year survivors (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p = 0.003, respectively). Median hepatic progression-free survival was longer in ≥3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008).\nConclusions\nHAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI DCE-MRI may predict treatment outcome.","Source":"Google Scholar","category":"HUMAN","training_data":"Regional Chemotherapy For Unresectable Intrahepatic Cholangiocarcinoma: A Potential Role For Dynamic Magnetic Resonance Imaging As An Imaging Biomarker And A Survival Update From Two Prospective Clinical Trials Background\nFor patients with unresectable intrahepatic cholangiocarcinoma (ICC), treatment options are limited and survival is poor. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine and dexamethasone (with or without bevacizumab) in advanced ICC.\nMethods\nProspectively collected clinicopathologic and survival data were retrospectively reviewed. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion data correlated with outcome.\nResults\nForty-four patients were analyzed (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3 months, 41 patients had died of disease. Partial response by RECIST was observed in 48 %, and 50 % had stable disease. Three patients underwent resection after response, and 82 % received additional HAI after removal from the trials. Median survival was similar in both trials (floxuridine 29.3 months vs. floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived ≥3 years, including 5 (11 %) who survived ≥5 years. Tumor perfusion measured on pre-treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s (AUC90 and AUC180, respectively)] was significantly higher in ≥3-year survivors and was the only factor that distinguished this group from <3-year survivors (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p = 0.003, respectively). Median hepatic progression-free survival was longer in ≥3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008).\nConclusions\nHAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI DCE-MRI may predict treatment outcome. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"glasgow prognostic score predicts poor prognosis among advanced biliary tract cancer patients good performance status advanced cancer patients good performance status ps sometimes show poor prognosis despite receiving chemotherapies evaluated prognosis chemo na ve advanced biliary tract cancer abtc patients good ps glasgow prognostic score gps sixty two patients eastern cooperative oncology group ps 0 1 retrospectively analyzed using multivariate cox regression gps defined serum levels two parameters albumin 3 5 g dl c reactive protein 1 0 mg dl 0 either 1 neither 2 ps 0 n 32 1 n 30 patients similar survival p 0 98 median overall survival os 17 0 months gps 0 n 19 14 2 months gps 1 n 17 6 4 months gps 2 n 26 gps 2 significantly shorter os gps 0 p 0 002 1 p 0 033 multivariate analysis identified two independent prognostic factors gps hazard ratio 0 60 95 confidence interval 0 40 0 90 p 0 012 liver metastasis hazard ratio 0 43 95 ci 0 20 0 90 p 0 026 gps useful chemo na ve abtc patients good ps pubmed","probabilities":0.9799733,"Title":"Glasgow Prognostic Score predicts poor prognosis among advanced biliary tract cancer patients with good performance status","Abstract":"Advanced cancer patients with good performance status (PS) sometimes show poor prognosis despite receiving some chemotherapies. We evaluated prognosis of chemo-naïve advanced biliary tract cancer (ABTC) patients with good PS by Glasgow Prognostic Score (GPS). Sixty-two patients with Eastern Cooperative Oncology Group PS 0 or 1 were retrospectively analyzed, using multivariate Cox regression. GPS was defined with serum levels of two parameters, albumin >3.5 g/dl and C-reactive protein <1.0 mg/dl (both as 0, either as 1, and neither as 2). PS 0 (n = 32) and 1 (n = 30) patients had similar survival (P = 0.98). The median overall survival (OS) was 17.0 months for GPS 0 (n = 19), 14.2 months for GPS 1 (n = 17), and 6.4 months for GPS 2 (n = 26). GPS 2 had significantly shorter OS than GPS 0 (P = 0.002) or 1 (P = 0.033). Multivariate analysis identified two independent prognostic factors: GPS (hazard ratio 0.60, 95 % confidence interval 0.40-0.90, P = 0.012) and liver metastasis (hazard ratio 0.43, 95 % CI 0.20-0.90, P = 0.026). GPS was useful for chemo-naïve ABTC patients with good PS.","Source":"PubMed","category":"HUMAN","training_data":"Glasgow Prognostic Score predicts poor prognosis among advanced biliary tract cancer patients with good performance status Advanced cancer patients with good performance status (PS) sometimes show poor prognosis despite receiving some chemotherapies. We evaluated prognosis of chemo-naïve advanced biliary tract cancer (ABTC) patients with good PS by Glasgow Prognostic Score (GPS). Sixty-two patients with Eastern Cooperative Oncology Group PS 0 or 1 were retrospectively analyzed, using multivariate Cox regression. GPS was defined with serum levels of two parameters, albumin >3.5 g/dl and C-reactive protein <1.0 mg/dl (both as 0, either as 1, and neither as 2). PS 0 (n = 32) and 1 (n = 30) patients had similar survival (P = 0.98). The median overall survival (OS) was 17.0 months for GPS 0 (n = 19), 14.2 months for GPS 1 (n = 17), and 6.4 months for GPS 2 (n = 26). GPS 2 had significantly shorter OS than GPS 0 (P = 0.002) or 1 (P = 0.033). Multivariate analysis identified two independent prognostic factors: GPS (hazard ratio 0.60, 95 % confidence interval 0.40-0.90, P = 0.012) and liver metastasis (hazard ratio 0.43, 95 % CI 0.20-0.90, P = 0.026). GPS was useful for chemo-naïve ABTC patients with good PS. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance preoperative platelet count patients gallbladder cancer aim investigate prognostic value preoperative platelet count plt patients primary gallbladder cancer gbc methods clinical data 223 gbc patients surgery retrospectively reviewed receiver operating characteristic roc curve plotted verify optimum cutoff point plt univariate multivariate survival analyses performed identify factors associated prognosis results roc curve showed optimum cutoff point plt 178 10 9 l entire cohort stratified group plt 178 10 9 l group b plt 178 10 9 l group better survival group b p 0 001 obvious difference two groups terms differentiation degree advanced tumor stage lymph node metastasis p 0 001 pathological type p 0 05 univariate analysis demonstrated tumor location differentiation degree tnm stage nevin stage lymph node metastasis plt associated overall survival p 0 001 multivariate analysis plt p 0 032 lymph node metastasis p 0 007 tumor location p 0 001 tnm stage p 0 005 independent prognostic factors conclusion plt closely correlated gbc prognosis used identify population poorer prognosis surgery pubmed","probabilities":0.9799733,"Title":"Prognostic significance of preoperative platelet count in patients with gallbladder cancer","Abstract":"AIM: To investigate the prognostic value of preoperative platelet count (PLT) in patients with primary gallbladder cancer (GBC). METHODS: The clinical data of 223 GBC patients after surgery was retrospectively reviewed. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cutoff point for PLT. Univariate and multivariate survival analyses were performed to identify the factors associated with the prognosis. RESULTS: The ROC curve showed that the optimum cutoff point for PLT was 178 × 10(9)/L, and the entire cohort was stratified into group A with PLT > 178 × 10(9)/L and group B with PLT ≤ 178 × 10(9)/L. Group A had a better survival than group B (P < 0.001). There was an obvious difference between the two groups in terms of the differentiation degree, advanced tumor stage, lymph node metastasis (P < 0.001) and pathological type (P < 0.05). The univariate analysis demonstrated that tumor location, differentiation degree, TNM stage, Nevin stage, lymph node metastasis and PLT were associated with overall survival (P < 0.001). In the multivariate analysis, PLT (P = 0.032), lymph node metastasis (P = 0.007), tumor location (P < 0.001) and TNM stage (P = 0.005) were independent prognostic factors. CONCLUSION: PLT is closely correlated with GBC prognosis and could be used to identify the population with a poorer prognosis after surgery.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of preoperative platelet count in patients with gallbladder cancer AIM: To investigate the prognostic value of preoperative platelet count (PLT) in patients with primary gallbladder cancer (GBC). METHODS: The clinical data of 223 GBC patients after surgery was retrospectively reviewed. A receiver operating characteristic (ROC) curve was plotted to verify the optimum cutoff point for PLT. Univariate and multivariate survival analyses were performed to identify the factors associated with the prognosis. RESULTS: The ROC curve showed that the optimum cutoff point for PLT was 178 × 10(9)/L, and the entire cohort was stratified into group A with PLT > 178 × 10(9)/L and group B with PLT ≤ 178 × 10(9)/L. Group A had a better survival than group B (P < 0.001). There was an obvious difference between the two groups in terms of the differentiation degree, advanced tumor stage, lymph node metastasis (P < 0.001) and pathological type (P < 0.05). The univariate analysis demonstrated that tumor location, differentiation degree, TNM stage, Nevin stage, lymph node metastasis and PLT were associated with overall survival (P < 0.001). In the multivariate analysis, PLT (P = 0.032), lymph node metastasis (P = 0.007), tumor location (P < 0.001) and TNM stage (P = 0.005) were independent prognostic factors. CONCLUSION: PLT is closely correlated with GBC prognosis and could be used to identify the population with a poorer prognosis after surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"serum albumin predicts survival patients hilar cholangiocarcinoma background aims hilar cholangiocarcinoma devastating malignancy incidence varying geography risk factors rapid progression disease delays diagnosis restrict number patients eligible curative therapy objective study determine prognostic factors overall survival patients presenting hilar cholangiocarcinoma methods adult patients histologically confirmed hilar cholangiocarcinoma 2003 2013 evaluated predictors survival using demographic factors laboratory data symptoms radiological characteristics presentation results total 116 patients identified pathological diagnosis hilar cholangiocarcinoma included analysis patients serum albumin level 3 0 g dl p 0 01 cancer antigen 19 9 200 u ml p 0 03 carcinoembryonic antigen 10 g l p 0 01 patients without history cirrhosis p 0 01 diabetes p 0 02 associated greater length overall survival serum albumin level 3 0 g dl identified independent predictor overall survival hazard ratio 0 31 95 confidence interval 0 14 0 70 survival benefit 44 weeks conclusion study largest analysis date prognostic factors patients hilar cholangiocarcinoma serum albumin level 3 0 g dl conferred independent survival advantage significantly greater length survival google scholar","probabilities":0.9799733,"Title":"Serum Albumin Predicts Survival In Patients With Hilar Cholangiocarcinoma","Abstract":"Background and aims: Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma.\nMethods: All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation.\nResults: A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P < 0.01), cancer antigen 19‐9 ≤200 U/mL (P = 0.03), carcinoembryonic antigen ≤10 ìg/L (P < 0.01) or patients without a history of cirrhosis (P < 0.01) or diabetes (P = 0.02) were associated with a greater length of overall survival. A serum albumin level >3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14–0.70) with a survival benefit of 44 weeks.\nConclusion: This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Serum Albumin Predicts Survival In Patients With Hilar Cholangiocarcinoma Background and aims: Hilar cholangiocarcinoma is a devastating malignancy with incidence varying by geography and other risk factors. Rapid progression of disease and delays in diagnosis restrict the number of patients eligible for curative therapy. The objective of this study was to determine prognostic factors of overall survival in all patients presenting with hilar cholangiocarcinoma.\nMethods: All adult patients with histologically confirmed hilar cholangiocarcinoma from 2003 to 2013 were evaluated for predictors of survival using demographic factors, laboratory data, symptoms and radiological characteristics at presentation.\nResults: A total of 116 patients were identified to have pathological diagnosis of hilar cholangiocarcinoma and were included in the analysis. Patients with a serum albumin level >3.0 g/dL (P < 0.01), cancer antigen 19‐9 ≤200 U/mL (P = 0.03), carcinoembryonic antigen ≤10 ìg/L (P < 0.01) or patients without a history of cirrhosis (P < 0.01) or diabetes (P = 0.02) were associated with a greater length of overall survival. A serum albumin level >3.0 g/dL was identified as an independent predictor of overall survival (hazard ratio 0.31; 95% confidence interval 0.14–0.70) with a survival benefit of 44 weeks.\nConclusion: This study was the largest analysis to date of prognostic factors in patients with hilar cholangiocarcinoma. A serum albumin level >3.0 g/dL conferred an independent survival advantage with a significantly greater length of survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"c reactive protein crp promising diagnostic immunohistochemical marker intrahepatic cholangiocarcinoma associated better prognosis differential diagnosis intrahepatic cholangiocarcinoma icca histologic mimickers especially metastatic adenocarcinomas gastric pancreatic origin great challenge pathologists study bioinformatics analysis data cancer genome atlas gene expression omnibus identified c reactive protein crp candidate marker differentiate icca adenocarcinomas validated diagnostic performance immunohistochemistry large cohort clinical samples including 103 iccas 384 adenocarcinomas 34 liver metastases various origins sensitivity specificity crp expression diagnosis icca 75 7 91 1 using tissue microarrays 93 3 88 2 using whole tissue sections respectively also compared diagnostic performance crp n cadherin previously reported marker icca sensitivity specificity n cadherin 54 4 92 2 using tissue microarrays 80 0 88 2 using whole tissue sections respectively sensitivity crp higher n cadherin whereas specificity similar crp expression associated mass forming gross type p 0 001 absence perineural invasion p 0 002 n cadherin expression p 0 001 crp expression also associated better overall survival p 0 002 longer recurrence free time p 0 032 surgery study suggests crp promising immunohistochemical marker differentiate icca adenocarcinomas compared n cadherin crp showed higher sensitivity similar specificity crp expression associated better prognosis icca pubmed","probabilities":0.7966102,"Title":"C-Reactive Protein (CRP) is a Promising Diagnostic Immunohistochemical Marker for Intrahepatic Cholangiocarcinoma and is Associated With Better Prognosis","Abstract":"Differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) from its histologic mimickers, especially metastatic adenocarcinomas of gastric and pancreatic origin, is a great challenge for pathologists. In this study, through bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus, we identified C-reactive protein (CRP) as a candidate marker to differentiate iCCA from other adenocarcinomas and validated its diagnostic performance by immunohistochemistry in a large cohort of clinical samples including 103 iCCAs, 384 other adenocarcinomas, and 34 liver metastases of various origins. The sensitivity and specificity of CRP expression in the diagnosis of iCCA were 75.7% and 91.1% when using tissue microarrays and 93.3% and 88.2% when using whole tissue sections, respectively. We also compared the diagnostic performance of CRP with N-cadherin, a previously reported marker for iCCA. The sensitivity and specificity of N-cadherin were 54.4% and 92.2% when using tissue microarrays and 80.0% and 88.2% when using whole tissue sections, respectively. The sensitivity of CRP was higher than that of N-cadherin, whereas their specificity was similar. CRP expression was associated with mass-forming gross type (P<0.001), absence of perineural invasion (P=0.002), and N-cadherin expression (P<0.001). CRP expression was also associated with better overall survival (P=0.002) and longer recurrence-free time (P=0.032) after surgery. Our study suggests that CRP is a promising immunohistochemical marker to differentiate iCCA from other adenocarcinomas. Compared with N-cadherin, CRP showed higher sensitivity and similar specificity. CRP expression was associated with better prognosis in iCCA.","Source":"PubMed","category":"ANIMAL","training_data":"C-Reactive Protein (CRP) is a Promising Diagnostic Immunohistochemical Marker for Intrahepatic Cholangiocarcinoma and is Associated With Better Prognosis Differential diagnosis of intrahepatic cholangiocarcinoma (iCCA) from its histologic mimickers, especially metastatic adenocarcinomas of gastric and pancreatic origin, is a great challenge for pathologists. In this study, through bioinformatics analysis of data from The Cancer Genome Atlas and Gene Expression Omnibus, we identified C-reactive protein (CRP) as a candidate marker to differentiate iCCA from other adenocarcinomas and validated its diagnostic performance by immunohistochemistry in a large cohort of clinical samples including 103 iCCAs, 384 other adenocarcinomas, and 34 liver metastases of various origins. The sensitivity and specificity of CRP expression in the diagnosis of iCCA were 75.7% and 91.1% when using tissue microarrays and 93.3% and 88.2% when using whole tissue sections, respectively. We also compared the diagnostic performance of CRP with N-cadherin, a previously reported marker for iCCA. The sensitivity and specificity of N-cadherin were 54.4% and 92.2% when using tissue microarrays and 80.0% and 88.2% when using whole tissue sections, respectively. The sensitivity of CRP was higher than that of N-cadherin, whereas their specificity was similar. CRP expression was associated with mass-forming gross type (P<0.001), absence of perineural invasion (P=0.002), and N-cadherin expression (P<0.001). CRP expression was also associated with better overall survival (P=0.002) and longer recurrence-free time (P=0.032) after surgery. Our study suggests that CRP is a promising immunohistochemical marker to differentiate iCCA from other adenocarcinomas. Compared with N-cadherin, CRP showed higher sensitivity and similar specificity. CRP expression was associated with better prognosis in iCCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"combination preoperative d dimer ca19 9 predicts lymph node metastasis survival intrahepatic cholangiocarcinoma patients curative resection background investigate predictive role d dimer combination preoperative ca19 9 lymph node metastasis lnm prognosis intrahepatic cholangiocarcinoma icc patients underwent curative intent resection methods one hundred seventy three patients admitted hospital april 2012 december 2018 included combination preoperative d dimer ca19 9 cpdc scored 0 decreased d dimer levels decreased ca19 9 levels 2 elevated d dimer levels elevated ca19 9 levels 1 combinations multivariate logistic regression analysis performed identify independent factors cox proportional hazard regression adopted multivariate survival analysis results cpdc score independent predictor lnm overall survival os multivariate analyses prediction lnm area curve auc cpdc score 0 722 95 ci 0 613 0 831 p 0 001 prediction survival auc cpdc score 0 756 95 ci 0 658 0 854 p 0 001 predictive capacity cpdc score higher d dimer ca19 9 kaplan meier curve analysis revealed cpdc 2 significantly associated worse os p 0 001 median os 8 00 versus 19 00 months versus reached shorter progression free survival pfs p 0 001 median pfs 4 00 versus 11 00 versus 15 00 months cpdc 1 cpdc 0 icc patients significant differences os comparisons two groups decreased preoperative cpdc associated worse os pfs subgroups except hbsag group cirrhosis hbsag tumour size 5 cm subgroups significant differences os pfs comparisons two groups conclusions preoperative cpdc score convenient powerful prognostic biomarker predict lnm os icc patients curative resection especially radiologically negative metastatic lymph node icc patients cpdc helpful assess extent lymph node dissection make follow plans stn","probabilities":0.9799733,"Title":"The Combination Of Preoperative D-Dimer And Ca19-9 Predicts Lymph Node Metastasis And Survival In Intrahepatic Cholangiocarcinoma Patients After Curative Resection","Abstract":"Background: To investigate the predictive role of D-dimer and its combination of preoperative CA19-9 for lymph node metastasis (LNM) and prognosis in intrahepatic cholangiocarcinoma (ICC) patients who underwent curative-intent resection. \n\n Methods: One hundred and seventy-three patients admitted to our hospital between April 2012 and December 2018 were included. The combination of preoperative D-dimer and CA19-9 (CPDC) was scored as 0 (decreased D-dimer levels with decreased CA19-9 levels), 2 (elevated D-dimer levels with elevated CA19-9 levels), or 1 (all other combinations). Multivariate logistic regression analysis was performed to identify independent factors. Cox proportional hazard regression was adopted for the multivariate survival analysis. \n\n Results: The CPDC score was an independent predictor of LNM and overall survival (OS) in the multivariate analyses. For the prediction of LNM, the area under the curve (AUC) for the CPDC score was 0.722 (95% CI: 0.613-0.831, P<0.001), and for the prediction of survival, the AUC for the CPDC score was 0.756 (95% CI: 0.658-0.854, P<0.001). The predictive capacity of the CPDC score was higher than that of D-dimer or CA19-9. Kaplan-Meier curve analysis revealed that a CPDC =2 was significantly associated with a worse OS (P<0.001, median OS: 8.00 versus 19.00 months versus not reached) and shorter progression-free survival (PFS) (P<0.001, median PFS: 4.00 versus 11.00 versus 15.00 months) than a CPDC =1 or CPDC =0 in ICC patients. There were significant differences in the OS comparisons between any two groups. Decreased preoperative CPDC was associated with worse OS and PFS in all subgroups except in the HBsAg (+) group. In the cirrhosis, HBsAg (-) and tumour size ≥5 cm subgroups, there were significant differences in the OS and PFS comparisons between any two groups. \n\n Conclusions: The preoperative CPDC score is a convenient and powerful prognostic biomarker to predict LNM and OS for ICC patients after curative resection. Especially for radiologically-negative metastatic lymph node in ICC patients, CPDC could be helpful to assess the extent of lymph node dissection and make follow-up plans.","Source":"STN","category":"HUMAN","training_data":"The Combination Of Preoperative D-Dimer And Ca19-9 Predicts Lymph Node Metastasis And Survival In Intrahepatic Cholangiocarcinoma Patients After Curative Resection Background: To investigate the predictive role of D-dimer and its combination of preoperative CA19-9 for lymph node metastasis (LNM) and prognosis in intrahepatic cholangiocarcinoma (ICC) patients who underwent curative-intent resection. \n\n Methods: One hundred and seventy-three patients admitted to our hospital between April 2012 and December 2018 were included. The combination of preoperative D-dimer and CA19-9 (CPDC) was scored as 0 (decreased D-dimer levels with decreased CA19-9 levels), 2 (elevated D-dimer levels with elevated CA19-9 levels), or 1 (all other combinations). Multivariate logistic regression analysis was performed to identify independent factors. Cox proportional hazard regression was adopted for the multivariate survival analysis. \n\n Results: The CPDC score was an independent predictor of LNM and overall survival (OS) in the multivariate analyses. For the prediction of LNM, the area under the curve (AUC) for the CPDC score was 0.722 (95% CI: 0.613-0.831, P<0.001), and for the prediction of survival, the AUC for the CPDC score was 0.756 (95% CI: 0.658-0.854, P<0.001). The predictive capacity of the CPDC score was higher than that of D-dimer or CA19-9. Kaplan-Meier curve analysis revealed that a CPDC =2 was significantly associated with a worse OS (P<0.001, median OS: 8.00 versus 19.00 months versus not reached) and shorter progression-free survival (PFS) (P<0.001, median PFS: 4.00 versus 11.00 versus 15.00 months) than a CPDC =1 or CPDC =0 in ICC patients. There were significant differences in the OS comparisons between any two groups. Decreased preoperative CPDC was associated with worse OS and PFS in all subgroups except in the HBsAg (+) group. In the cirrhosis, HBsAg (-) and tumour size ≥5 cm subgroups, there were significant differences in the OS and PFS comparisons between any two groups. \n\n Conclusions: The preoperative CPDC score is a convenient and powerful prognostic biomarker to predict LNM and OS for ICC patients after curative resection. Especially for radiologically-negative metastatic lymph node in ICC patients, CPDC could be helpful to assess the extent of lymph node dissection and make follow-up plans. STN","prediction_labels":"HUMAN"},{"cleaned":"spontaneous production glutathione conjugated forms 12 dichloropropane comparative study metabolic activation processes dihaloalkanes associated occupational cholangiocarcinoma recently epidemiological studies revealed positive relationship outbreak occupational cholangiocarcinoma exposure organic solvents containing 1 2 dichloropropane 1 2 dcp 1 2 dcp administered animal models previously found biliary excretion potentially oncogenic metabolites consisting glutathione gsh conjugated forms 1 2 dcp gs dcps however gs dcp production pathway remains unknown enhance understanding 1 2 dcp related risks human health examined reactivity gsh 1 2 dcp vitro compared dichloromethane dcm putative substance responsible occupational cholangiocarcinoma results showed 1 2 dcp spontaneously conjugated gsh whereas spontaneous reaction hardly detected dcm gsh analysis revealed glutathione transferase theta 1 gstt1 exhibited less effect 1 2 dcp reaction compared observed dcm although gstt1 mediated bioactivation dihaloalkanes plausible explanation production reactive metabolites related carcinogenesis based previous studies catalytic pathway might mainly contribute 1 2 dcp related occupational cholangiocarcinoma considering higher catalytic activity gstt1 dcm compared 1 2 dcp findings suggested differences activation processes associated 1 2 dcp dcm metabolism stn","probabilities":1.0,"Title":"Spontaneous Production Of Glutathione-Conjugated Forms Of 12-Dichloropropane: Comparative Study On Metabolic Activation Processes Of Dihaloalkanes Associated With Occupational Cholangiocarcinoma","Abstract":"Recently, epidemiological studies revealed a positive relationship between an outbreak of occupational cholangiocarcinoma and exposure to organic solvents containing 1,2-dichloropropane (1,2-DCP). In 1,2-DCP-administered animal models, we previously found biliary excretion of potentially oncogenic metabolites consisting of glutathione- (GSH-) conjugated forms of 1,2-DCP (GS-DCPs); however, the GS-DCP production pathway remains unknown. To enhance the understanding of 1,2-DCP-related risks to human health, we examined the reactivity of GSH with 1,2-DCP in vitro and compared it to that with dichloromethane (DCM), the other putative substance responsible for occupational cholangiocarcinoma. Our results showed that 1,2-DCP was spontaneously conjugated with GSH, whereas this spontaneous reaction was hardly detected between DCM and GSH. Further analysis revealed that glutathione S-transferase theta 1 (GSTT1) exhibited less effect on the 1,2-DCP reaction as compared with that observed for DCM. Although GSTT1-mediated bioactivation of dihaloalkanes could be a plausible explanation for the production of reactive metabolites related to carcinogenesis based on previous studies, this catalytic pathway might not mainly contribute to 1,2-DCP-related occupational cholangiocarcinoma. Considering the higher catalytic activity of GSTT1 on DCM as compared with that on 1,2-DCP, our findings suggested differences in the activation processes associated with 1,2-DCP and DCM metabolism.","Source":"STN","category":"ANIMAL","training_data":"Spontaneous Production Of Glutathione-Conjugated Forms Of 12-Dichloropropane: Comparative Study On Metabolic Activation Processes Of Dihaloalkanes Associated With Occupational Cholangiocarcinoma Recently, epidemiological studies revealed a positive relationship between an outbreak of occupational cholangiocarcinoma and exposure to organic solvents containing 1,2-dichloropropane (1,2-DCP). In 1,2-DCP-administered animal models, we previously found biliary excretion of potentially oncogenic metabolites consisting of glutathione- (GSH-) conjugated forms of 1,2-DCP (GS-DCPs); however, the GS-DCP production pathway remains unknown. To enhance the understanding of 1,2-DCP-related risks to human health, we examined the reactivity of GSH with 1,2-DCP in vitro and compared it to that with dichloromethane (DCM), the other putative substance responsible for occupational cholangiocarcinoma. Our results showed that 1,2-DCP was spontaneously conjugated with GSH, whereas this spontaneous reaction was hardly detected between DCM and GSH. Further analysis revealed that glutathione S-transferase theta 1 (GSTT1) exhibited less effect on the 1,2-DCP reaction as compared with that observed for DCM. Although GSTT1-mediated bioactivation of dihaloalkanes could be a plausible explanation for the production of reactive metabolites related to carcinogenesis based on previous studies, this catalytic pathway might not mainly contribute to 1,2-DCP-related occupational cholangiocarcinoma. Considering the higher catalytic activity of GSTT1 on DCM as compared with that on 1,2-DCP, our findings suggested differences in the activation processes associated with 1,2-DCP and DCM metabolism. STN","prediction_labels":"ANIMAL"},{"cleaned":"global trends mortality intrahepatic extrahepatic cholangiocarcinoma background aims intrahepatic icc extrahepatic cholangiocarcinoma ecc rarely studied individually probably due difficulties diagnosis certification mortality trends 2 neoplasms inconsistent last decades aim study analyze worldwide trends mortality icc ecc selected countries methods extracted death certification data icc ecc population estimates world health organization pan american health organization databases 32 selected countries europe americas australasia 1995 2016 computed age standardized world population mortality rates icc ecc performed joinpoint regression analysis results mortality rates icc increased countries considered levelling recent years germany women italy men argentina men usa men hong kong men japan sexes highest rates 2010 2014 1 5 2 5 100 000 men 1 2 1 7 100 000 women registered hong kong france austria spain uk australia lowest rates 0 2 0 6 100 000 sexes registered latin american eastern european countries mortality ecc decreased countries considered rates 1 100 000 sexes 2010 2014 exception japan 2 8 100 000 men 1 4 100 000 women conclusions increasing mortality icc observed globally due trends risk factors possibly part due better disease classification mortality ecc levelled decreased likely following increased use laparoscopic cholecystectomy google scholar","probabilities":0.9799733,"Title":"Global Trends In Mortality From Intrahepatic And Extrahepatic Cholangiocarcinoma","Abstract":"Background & Aims\nIntrahepatic (ICC) and extrahepatic cholangiocarcinoma (ECC) have rarely been studied individually, probably due to difficulties in their diagnosis and certification. Mortality trends from these 2 neoplasms have been inconsistent over the last decades. The aim of this study was to analyze worldwide trends in mortality from ICC and ECC in selected countries.\nMethods\nWe extracted death certification data for ICC and ECC, and population estimates from the World Health Organization and Pan American Health Organization databases for 32 selected countries from Europe, the Americas, and Australasia from 1995 to 2016. We computed age-standardized (world population) mortality rates from ICC and ECC, and performed joinpoint regression analysis.\nResults\nMortality rates from ICC increased in all countries considered, with a levelling off over recent years in Germany (women), Italy (men), Argentina (men), the USA (men), Hong Kong (men), and Japan (both sexes). The highest rates in 2010–2014 (1.5–2.5/100,000 in men and 1.2–1.7/100,000 in women) were registered in Hong Kong, France, Austria, Spain, the UK, and Australia. The lowest rates (0.2–0.6/100,000 in both sexes) were registered in Latin American and eastern European countries. Mortality from ECC decreased in most of the countries considered, with rates below 1/100,000 in both sexes between 2010 and 2014, with the only exception being Japan (2.8/100,000 in men and 1.4/100,000 in women).\nConclusions\nIncreasing mortality from ICC was observed globally, due to trends in risk factors and possibly, in part, due to better disease classification. Mortality from ECC levelled off or decreased, most likely following the increased use of laparoscopic cholecystectomy.","Source":"Google Scholar","category":"HUMAN","training_data":"Global Trends In Mortality From Intrahepatic And Extrahepatic Cholangiocarcinoma Background & Aims\nIntrahepatic (ICC) and extrahepatic cholangiocarcinoma (ECC) have rarely been studied individually, probably due to difficulties in their diagnosis and certification. Mortality trends from these 2 neoplasms have been inconsistent over the last decades. The aim of this study was to analyze worldwide trends in mortality from ICC and ECC in selected countries.\nMethods\nWe extracted death certification data for ICC and ECC, and population estimates from the World Health Organization and Pan American Health Organization databases for 32 selected countries from Europe, the Americas, and Australasia from 1995 to 2016. We computed age-standardized (world population) mortality rates from ICC and ECC, and performed joinpoint regression analysis.\nResults\nMortality rates from ICC increased in all countries considered, with a levelling off over recent years in Germany (women), Italy (men), Argentina (men), the USA (men), Hong Kong (men), and Japan (both sexes). The highest rates in 2010–2014 (1.5–2.5/100,000 in men and 1.2–1.7/100,000 in women) were registered in Hong Kong, France, Austria, Spain, the UK, and Australia. The lowest rates (0.2–0.6/100,000 in both sexes) were registered in Latin American and eastern European countries. Mortality from ECC decreased in most of the countries considered, with rates below 1/100,000 in both sexes between 2010 and 2014, with the only exception being Japan (2.8/100,000 in men and 1.4/100,000 in women).\nConclusions\nIncreasing mortality from ICC was observed globally, due to trends in risk factors and possibly, in part, due to better disease classification. Mortality from ECC levelled off or decreased, most likely following the increased use of laparoscopic cholecystectomy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"role purinergic receptors hepatobiliary carcinoma pakistani population approach towards proinflammatory role p2x4 p2x7 receptors primary malignancy liver known hepatocellular carcinoma hcc comprises 9 hepatobiliary carcinomas steady rise also observed adenocarcinoma adc liver ampullary carcinoma amc ascending 0 5 gastrointestinal malignancies hepatobiliary carcinomas consist 13 cancer occurrences worldwide purinergic receptor based signaling holds therapeutic potential based role cell proliferation several carcinomas altered atp concentration nanomoles may lead towards crucial changes cancer growth patterns liver tissue total 40 tissue samples collected 20 samples hcc 10 samples adc 10 samples amc patients underwent surgery p2x4 p2x7 receptors exhibited significantly increased expression hcc adc amc samples compared control tissue samples adc amc samples showed higher expression p2x4 p2x7 control statistically hcc samples exhibited significant expression p2x4 p2x7 receptors control tissues may inferred higher expression p2x4 p2x7 receptors significantly associated upregulated cellular stress leading inflammation plausible receptors may used diagnostic prognostic therapeutic tools carcinoma studies future stn","probabilities":0.9467213,"Title":"Role Of Purinergic Receptors In Hepatobiliary Carcinoma In Pakistani Population: An Approach Towards Proinflammatory Role Of P2X4 And P2X7 Receptors","Abstract":"The primary malignancy of liver, known as hepatocellular carcinoma (HCC), comprises 9% of all hepatobiliary carcinomas. A steady rise has also been observed in adenocarcinoma (ADC) of the liver and ampullary carcinoma (AMC), ascending to 0.5% of gastrointestinal malignancies. Hepatobiliary carcinomas consist of 13% of all cancer occurrences worldwide. Purinergic receptor-based signaling holds the therapeutic potential based on its role in cell proliferation of several carcinomas. An altered ATP concentration in nanomoles may lead towards crucial changes in cancer growth patterns in liver tissue. A total of 40 tissue samples were collected (20 samples of HCC, 10 samples of ADC, and 10 samples of AMC) from patients that underwent surgery. P2X4 and P2X7 receptors exhibited significantly increased expression in HCC, ADC, and AMC samples as compared with the control tissue samples. While ADC and AMC samples showed higher expression of P2X4 and P2X7 than the control, statistically, HCC samples exhibited the most significant expression of both P2X4 and P2X7 receptors than control tissues. It may be inferred that higher expression of P2X4 and P2X7 receptors is significantly associated with the upregulated cellular stress leading to inflammation and it is plausible that both these receptors may be used in diagnostic, prognostic, and therapeutic tools for carcinoma studies in the future.","Source":"STN","category":"ANIMAL","training_data":"Role Of Purinergic Receptors In Hepatobiliary Carcinoma In Pakistani Population: An Approach Towards Proinflammatory Role Of P2X4 And P2X7 Receptors The primary malignancy of liver, known as hepatocellular carcinoma (HCC), comprises 9% of all hepatobiliary carcinomas. A steady rise has also been observed in adenocarcinoma (ADC) of the liver and ampullary carcinoma (AMC), ascending to 0.5% of gastrointestinal malignancies. Hepatobiliary carcinomas consist of 13% of all cancer occurrences worldwide. Purinergic receptor-based signaling holds the therapeutic potential based on its role in cell proliferation of several carcinomas. An altered ATP concentration in nanomoles may lead towards crucial changes in cancer growth patterns in liver tissue. A total of 40 tissue samples were collected (20 samples of HCC, 10 samples of ADC, and 10 samples of AMC) from patients that underwent surgery. P2X4 and P2X7 receptors exhibited significantly increased expression in HCC, ADC, and AMC samples as compared with the control tissue samples. While ADC and AMC samples showed higher expression of P2X4 and P2X7 than the control, statistically, HCC samples exhibited the most significant expression of both P2X4 and P2X7 receptors than control tissues. It may be inferred that higher expression of P2X4 and P2X7 receptors is significantly associated with the upregulated cellular stress leading to inflammation and it is plausible that both these receptors may be used in diagnostic, prognostic, and therapeutic tools for carcinoma studies in the future. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic role glycolysis cancer outcome evidence 86 studies objective abnormal expression key enzymes glycolytic pathways including glucose transporter 1 glucose transporter 3 hexokinase ii lactate dehydrogenase 5 pyruvate kinase m2 glucose 6 phosphate dehydrogenase transketolase like protein 1 pyruvate dehydrogenase kinase 1 reported associated poor prognosis various cancers however association remains controversial objective study investigate prognostic significance glycolysis related proteins materials methods searched medline embase cochrane database systematic reviews cochrane central register controlled trials using pubmed ovid search engines google scholar inception april 2017 eighty six studies 12 002 patients included study results pooled results identified glycolysis related proteins cancers associated shorter overall survival colorectal cancer hr 2 33 95 ci 1 38 3 93 p 0 002 gastric cancer hr 1 55 95 ci 1 31 1 82 p 0 001 cancer gallbladder bile duct hr 2 16 95 ci 1 70 2 75 p 0 001 oral cancer hr 2 07 95 ci 1 32 3 25 p 0 001 esophageal cancer hr 1 66 95 ci 1 25 2 21 p 0 01 hepatocellular carcinoma hr 2 04 95 ci 1 64 2 54 p 0 001 pancreatic cancer hr 1 72 95 ci 1 39 2 13 p 0 001 breast cancer hr 1 67 95 ci 1 34 2 08 p 0 001 nasopharyngeal carcinoma hr 3 59 95 ci 1 75 7 36 p 0 001 association found lung cancer ovarian cancer melanoma key glycolytic transcriptional regulators hif 1 p53 analyzed parallel glycolysis related proteins pooled results identified high level expression hif 1 significantly associated shorter overall survival hr 0 57 95 ci 0 42 0 79 p 0 001 furthermore glycolysis related proteins linked poor differentiated tumors 1 81 95 ci 1 46 2 25 p 0 001 positive lymph node metastasis 2 73 95 ci 2 16 3 46 p 0 001 positive vascular invasion 2 05 95 ci 1 37 3 07 p 0 001 large tumor size 2 06 95 ci 1 80 2 37 p 0 001 advanced tumor stage 1 58 95 ci 1 19 2 09 p 0 001 deeper invasion 2 37 95 ci 1 93 2 91 p 0 001 conclusion glycolytic transcriptional regulators glycolysis related proteins cancers significantly associated poor prognosis suggesting glycolytic status may potentially valuable prognostic biomarkers various cancers pubmed","probabilities":0.9799733,"Title":"Prognostic role of glycolysis for cancer outcome: evidence from 86 studies","Abstract":"OBJECTIVE: The abnormal expression of the key enzymes in glycolytic pathways, including glucose transporter-1, glucose transporter-3, hexokinase-II, lactate dehydrogenase 5, pyruvate kinase M2, glucose-6-phosphate dehydrogenase, transketolase-like protein 1 and pyruvate dehydrogenase kinase-1 was reported to be associated with poor prognosis of various cancers. However, the association remains controversial. The objective of this study was to investigate the prognostic significance of glycolysis-related proteins. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, using Pubmed and Ovid as search engines and Google Scholar from inception to April 2017. Eighty-six studies with 12,002 patients were included in the study. RESULTS: Our pooled results identified that glycolysis-related proteins in cancers were associated with shorter overall survival of colorectal cancer (HR 2.33, 95% CI 1.38-3.93, P = 0.002), gastric cancer (HR 1.55, 95% CI 1.31-1.82, P < 0.001), cancer of gallbladder or bile duct (HR 2.16, 95% CI 1.70-2.75, P < 0.001), oral cancer (HR 2.07, 95% CI 1.32-3.25, P < 0.001), esophageal cancer (HR 1.66, 95% CI 1.25-2.21, P = 0.01), hepatocellular carcinoma (HR 2.04, 95% CI 1.64-2.54, P < 0.001), pancreatic cancer (HR 1.72, 95% CI 1.39-2.13, P < 0.001), breast cancer(HR 1.67, 95% CI 1.34-2.08, P < 0.001), and nasopharyngeal carcinoma (HR 3.59, 95% CI 1.75-7.36, P < 0.001). No association was found for lung cancer, ovarian cancer or melanoma. The key glycolytic transcriptional regulators (HIF-1α, p53) were analyzed in parallel to the glycolysis-related proteins, and the pooled results identified that high-level expression of HIF-1α was significantly associated with shorter overall survival (HR 0.57, 95% CI 0.42-0.79, P < 0.001) Furthermore, glycolysis-related proteins linked with poor differentiated tumors (OR 1.81, 95% CI 1.46-2.25, P < 0.001), positive lymph node metastasis (OR 2.73, 95% CI 2.16-3.46, P < 0.001), positive vascular invasion (OR 2.05, 95% CI 1.37-3.07, P < 0.001), large tumor size (OR 2.06, 95% CI 1.80-2.37, P < 0.001), advanced tumor stage (OR 1.58, 95% CI 1.19-2.09, P < 0.001), and deeper invasion (OR 2.37, 95% CI 1.93-2.91, P < 0.001). CONCLUSION: Glycolytic transcriptional regulators and glycolysis-related proteins in cancers were significantly associated with poor prognosis, suggesting glycolytic status may be potentially valuable prognostic biomarkers for various cancers.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic role of glycolysis for cancer outcome: evidence from 86 studies OBJECTIVE: The abnormal expression of the key enzymes in glycolytic pathways, including glucose transporter-1, glucose transporter-3, hexokinase-II, lactate dehydrogenase 5, pyruvate kinase M2, glucose-6-phosphate dehydrogenase, transketolase-like protein 1 and pyruvate dehydrogenase kinase-1 was reported to be associated with poor prognosis of various cancers. However, the association remains controversial. The objective of this study was to investigate the prognostic significance of glycolysis-related proteins. MATERIALS AND METHODS: We searched MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, using Pubmed and Ovid as search engines and Google Scholar from inception to April 2017. Eighty-six studies with 12,002 patients were included in the study. RESULTS: Our pooled results identified that glycolysis-related proteins in cancers were associated with shorter overall survival of colorectal cancer (HR 2.33, 95% CI 1.38-3.93, P = 0.002), gastric cancer (HR 1.55, 95% CI 1.31-1.82, P < 0.001), cancer of gallbladder or bile duct (HR 2.16, 95% CI 1.70-2.75, P < 0.001), oral cancer (HR 2.07, 95% CI 1.32-3.25, P < 0.001), esophageal cancer (HR 1.66, 95% CI 1.25-2.21, P = 0.01), hepatocellular carcinoma (HR 2.04, 95% CI 1.64-2.54, P < 0.001), pancreatic cancer (HR 1.72, 95% CI 1.39-2.13, P < 0.001), breast cancer(HR 1.67, 95% CI 1.34-2.08, P < 0.001), and nasopharyngeal carcinoma (HR 3.59, 95% CI 1.75-7.36, P < 0.001). No association was found for lung cancer, ovarian cancer or melanoma. The key glycolytic transcriptional regulators (HIF-1α, p53) were analyzed in parallel to the glycolysis-related proteins, and the pooled results identified that high-level expression of HIF-1α was significantly associated with shorter overall survival (HR 0.57, 95% CI 0.42-0.79, P < 0.001) Furthermore, glycolysis-related proteins linked with poor differentiated tumors (OR 1.81, 95% CI 1.46-2.25, P < 0.001), positive lymph node metastasis (OR 2.73, 95% CI 2.16-3.46, P < 0.001), positive vascular invasion (OR 2.05, 95% CI 1.37-3.07, P < 0.001), large tumor size (OR 2.06, 95% CI 1.80-2.37, P < 0.001), advanced tumor stage (OR 1.58, 95% CI 1.19-2.09, P < 0.001), and deeper invasion (OR 2.37, 95% CI 1.93-2.91, P < 0.001). CONCLUSION: Glycolytic transcriptional regulators and glycolysis-related proteins in cancers were significantly associated with poor prognosis, suggesting glycolytic status may be potentially valuable prognostic biomarkers for various cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"chemotherapy versus best supportive care advanced biliary tract carcinoma multi institutional propensity score matching analysis purpose although chemotherapy recommended various guidelines advanced biliary tract cancer btc evidence supporting use best supportive care bsc limited aim study investigate survival benefit chemotherapy bsc advanced btc patients materials methods advanced btc patientswith good performance status eastern cooperativeoncologygroup ecog 0 2 eligible study data retrospectively collected four tertiary cancer centers analyzed using propensity score matching psm 604 patients enrolled 206 received bsc 398 received chemotherapy psm analysis performed using following variables age ecog status carcinoembryonic antigen cea level white blood cell level albumin level total bilirubin level aspartate aminotransferase level sample size group 164 patients psm median survival compared two groups using kaplan meier method prognostic factors investigated using cox proportional regression analysis results post psm analysis respective median survival chemotherapy bsc groups dependent following prognostic factors total population 12 0 months vs 7 5 months p 0 001 locally advanced disease 16 7 months vs 13 4 months p 0 490 cancer antigen 19 9 100 iu ml 12 7 months vs 10 6 months p 0 330 cea 3 4 ng ml 17 1 months vs 10 6 months p 0 052 conclusion chemotherapy improved overall survival patients advanced btc good performance status however survival benefit observed btc patients locally advanced disease lower tumor marker individualized approach needed initiation palliative chemotherapy advanced btc pubmed","probabilities":0.962963,"Title":"Chemotherapy versus Best Supportive Care in Advanced Biliary Tract Carcinoma: A Multi-institutional Propensity Score Matching Analysis","Abstract":"PURPOSE: Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. MATERIALS AND METHODS: Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. RESULTS: In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). CONCLUSION: Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC.","Source":"PubMed","category":"HUMAN","training_data":"Chemotherapy versus Best Supportive Care in Advanced Biliary Tract Carcinoma: A Multi-institutional Propensity Score Matching Analysis PURPOSE: Although chemotherapy is recommended by various guidelines for advanced biliary tract cancer (BTC), the evidence supporting its use over best supportive care (BSC) is limited. The aim of this study was to investigate the survival benefit of chemotherapy over that of BSC in advanced BTC patients. MATERIALS AND METHODS: Advanced BTC patientswith a good performance status (Eastern CooperativeOncologyGroup [ECOG] 0-2) were eligible for the study. Data were retrospectively collected from four tertiary cancer centers and analyzed using propensity score matching (PSM). Of the 604 patients enrolled, 206 received BSC and 398 received chemotherapy. PSM analysis was performed using the following variables: age, ECOG status, carcinoembryonic antigen (CEA) level, white blood cell level, albumin level, total bilirubin level, and aspartate aminotransferase level. The sample size of each group was 164 patients after PSM. Median survival was compared between the two groups by using the Kaplan-Meier method, and prognostic factors were investigated using Cox proportional regression analysis. RESULTS: In post-PSM analysis, the respective median survival for the chemotherapy and BSC groups was dependent on the following prognostic factors: total population, 12.0 months vs. 7.5 months (p=0.001); locally advanced disease, 16.7 months vs. 13.4 months (p=0.490); cancer antigen 19-9 ≤ 100 IU/mL, 12.7 months vs. 10.6 months (p=0.330); and CEA ≤ 3.4 ng/mL, 17.1 months vs. 10.6 months (p=0.052). CONCLUSION: Chemotherapy improved overall survival of patients with advanced BTC who had a good performance status. However, this survival benefit was not observed in BTC patients with locally advanced disease or with lower tumor marker. Individualized approach is needed for initiation of palliative chemotherapy in advanced BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effects aspirin non steroidal anti inflammatory drugs risk cholangiocarcinoma meta analysis background non steroidal anti inflammatory drugs nsaids suppress proliferation cholangiocarcinoma cca cells vitro inhibition cyclooxygenase 2 however effects aspirin nsaids risk cca remain unclear performed meta analysis assess risk biliary tract cancers patients take aspirin nsaids methods systematic review conducted utilizing medline embase cochrane databases inception october 2017 identify studies assessed association aspirin nsaids use risk biliary tract cancers including cca gallbladder cancer ampulla vater cancer effect estimates studies extracted combined using random effect generic inverse variance method dersimonian laird results five observational studies total 9 200 653 patients enrolled pooled cca patients aspirin use 0 56 95 ci 0 32 0 96 egger regression asymmetry test performed showed publication bias association aspirin use cca p 0 42 significant association nsaids use cca pooled 0 79 95 ci 0 28 2 21 one study showed significant association aspirin use reduced risk gallbladder cancer 0 37 0 17 0 80 however significant association aspirin ampulla vater cancer 0 22 0 03 1 65 conclusions study demonstrates significant association aspirin use 0 56 fold decreased risk cca however association use nsaids cca pubmed","probabilities":0.9799733,"Title":"Effects of aspirin and non-steroidal anti-inflammatory drugs on the risk of cholangiocarcinoma: a meta-analysis","Abstract":"BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can suppress the proliferation of cholangiocarcinoma (CCA) cells in vitro through inhibition of cyclooxygenase-2. However, the effects of aspirin and NSAIDs on the risk of CCA remain unclear. We performed this meta-analysis to assess the risk of biliary tract cancers in patients who take aspirin and/or NSAIDs. METHODS: A systematic review was conducted utilizing MEDLINE, EMBASE, Cochrane databases from inception through October 2017 to identify studies that assessed the association of aspirin and/or NSAIDs use with risk of biliary tract cancers including CCA, gallbladder cancer and ampulla of Vater cancer. Effect estimates from the studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Five observational studies with a total of 9 200 653 patients were enrolled. The pooled OR of CCA in patients with aspirin use was 0.56 (95% CI, 0.32-0.96). Egger's regression asymmetry test was performed and showed no publication bias for the association between aspirin use and CCA with P = 0.42. There was no significant association between NSAIDs use and CCA, with a pooled OR of 0.79 (95% CI, 0.28-2.21). One study showed a significant association between aspirin use and reduced risk of gallbladder cancer with OR of 0.37 (0.17-0.80). However, there was no significant association between aspirin and ampulla of Vater cancer with OR of 0.22 (0.03-1.65). CONCLUSIONS: Our study demonstrates a significant association between aspirin use and a 0.56-fold decreased risk of CCA. However, there is no association between the use of NSAIDs and CCA.","Source":"PubMed","category":"HUMAN","training_data":"Effects of aspirin and non-steroidal anti-inflammatory drugs on the risk of cholangiocarcinoma: a meta-analysis BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) can suppress the proliferation of cholangiocarcinoma (CCA) cells in vitro through inhibition of cyclooxygenase-2. However, the effects of aspirin and NSAIDs on the risk of CCA remain unclear. We performed this meta-analysis to assess the risk of biliary tract cancers in patients who take aspirin and/or NSAIDs. METHODS: A systematic review was conducted utilizing MEDLINE, EMBASE, Cochrane databases from inception through October 2017 to identify studies that assessed the association of aspirin and/or NSAIDs use with risk of biliary tract cancers including CCA, gallbladder cancer and ampulla of Vater cancer. Effect estimates from the studies were extracted and combined using the random-effect, generic inverse variance method of DerSimonian and Laird. RESULTS: Five observational studies with a total of 9 200 653 patients were enrolled. The pooled OR of CCA in patients with aspirin use was 0.56 (95% CI, 0.32-0.96). Egger's regression asymmetry test was performed and showed no publication bias for the association between aspirin use and CCA with P = 0.42. There was no significant association between NSAIDs use and CCA, with a pooled OR of 0.79 (95% CI, 0.28-2.21). One study showed a significant association between aspirin use and reduced risk of gallbladder cancer with OR of 0.37 (0.17-0.80). However, there was no significant association between aspirin and ampulla of Vater cancer with OR of 0.22 (0.03-1.65). CONCLUSIONS: Our study demonstrates a significant association between aspirin use and a 0.56-fold decreased risk of CCA. However, there is no association between the use of NSAIDs and CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"management incidentally detected gallbladder carcinomas high prevalence area gallbladder cancer background increasing incidence advanced unresectable gallbladder cancer even patients undergo re exploration cases marked poor survival even undergoing curative resection adjuvant chemotherapy lack suspicion primary surgery unavailability frozen section facilities delayed referrals believed contribute high incidence aim aim evaluate results re surgery incidental gallbladder cancers detected open laparoscopic cholecystectomy assess outcome patients underwent complete radical cholecystectomy adjuvant therapy method retrospectively analyzed data prospectively maintained computerized database patients incidentally detected gallbladder cancers operated department surgical oncology june 2006 january 2013 results forty two patients incidental gallbladder cancer re explored median time re exploration initial surgery 65 days eighteen 43 patients found inoperable due locally advanced unresectable metastatic disease among 24 57 patients underwent completion radical cholecystectomy 11 developed recurrence median time 11 months conclusion despite dismal prognosis half incidentally detected gallbladder carcinoma patients receive curative treatment identification patients incidentally discovered gallbladder cancer early referral oncology center may ensure patients receive curative resection thereby increasing chances long term disease free survival pubmed","probabilities":0.9799733,"Title":"Management of incidentally detected gallbladder carcinomas in a high prevalence area of gallbladder cancer","Abstract":"BACKGROUND: There is an increasing incidence of advanced unresectable gallbladder cancer even in patients who undergo re-exploration and these cases are marked by poor survival even after undergoing curative resection and adjuvant chemotherapy. Lack of suspicion during primary surgery, unavailability of frozen section facilities and delayed referrals are believed to contribute to this high incidence. AIM: Our aim was to evaluate the results of re-surgery in incidental gallbladder cancers detected after open or laparoscopic cholecystectomy and to assess the outcome in patients who underwent complete radical cholecystectomy and adjuvant therapy. METHOD: We retrospectively analyzed the data from a prospectively maintained computerized database of all patients with incidentally detected gallbladder cancers operated in the Department of Surgical Oncology, from June 2006 to January 2013. RESULTS: Forty-two patients with incidental gallbladder cancer were re-explored. The median time of re-exploration after initial surgery was 65 days. Eighteen (43%) patients were found inoperable due to locally advanced unresectable or metastatic disease. Among the 24 (57%) patients who underwent completion radical cholecystectomy, 11 developed recurrence over a median time of 11 months. CONCLUSION: Despite the dismal prognosis, more than half of the incidentally detected gallbladder carcinoma patients could receive curative treatment. Identification of patients with incidentally discovered gallbladder cancer and early referral to an oncology center may ensure these patients receive curative resection thereby increasing their chances for long-term disease free survival.","Source":"PubMed","category":"HUMAN","training_data":"Management of incidentally detected gallbladder carcinomas in a high prevalence area of gallbladder cancer BACKGROUND: There is an increasing incidence of advanced unresectable gallbladder cancer even in patients who undergo re-exploration and these cases are marked by poor survival even after undergoing curative resection and adjuvant chemotherapy. Lack of suspicion during primary surgery, unavailability of frozen section facilities and delayed referrals are believed to contribute to this high incidence. AIM: Our aim was to evaluate the results of re-surgery in incidental gallbladder cancers detected after open or laparoscopic cholecystectomy and to assess the outcome in patients who underwent complete radical cholecystectomy and adjuvant therapy. METHOD: We retrospectively analyzed the data from a prospectively maintained computerized database of all patients with incidentally detected gallbladder cancers operated in the Department of Surgical Oncology, from June 2006 to January 2013. RESULTS: Forty-two patients with incidental gallbladder cancer were re-explored. The median time of re-exploration after initial surgery was 65 days. Eighteen (43%) patients were found inoperable due to locally advanced unresectable or metastatic disease. Among the 24 (57%) patients who underwent completion radical cholecystectomy, 11 developed recurrence over a median time of 11 months. CONCLUSION: Despite the dismal prognosis, more than half of the incidentally detected gallbladder carcinoma patients could receive curative treatment. Identification of patients with incidentally discovered gallbladder cancer and early referral to an oncology center may ensure these patients receive curative resection thereby increasing their chances for long-term disease free survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"mucins differently expressed various ampullary adenocarcinomas background investigated occurrence clinical significance mucin expression ampullary adenocarcinoma methods retrospectively analyzed clinical pathological survival data 74 ampullary adenocarcinoma patients received radical operation january 2004 november 2006 results tumors located lower end common bile duct 46 papillary duodenum 42 ampullary duodenum 12 expressed muc1 72 muc2 20 muc5ac 43 muc6 27 expression muc1 associated tumor differentiation 4 71 95 ci 1 26 17 66 p 0 021 expression muc5ac associated age 1 07 95 ci 1 11 1 14 p 0 026 less vessel invasion 0 14 95 ci 0 03 0 72 p 0 019 survival rates significantly different patients expression muc1 muc2 muc5ac muc6 tumor patients tumors positive muc5ac papillary duodenum worse survival tumors negative muc5ac p 0 044 conclusions expression muc1 high 72 ampullary adenocarcinoma expressions muc2 muc5ac muc6 lower mucins useful markers diagnose identify ampullary adenocarcinoma particularly determining degree malignancy ampullary adenocarcinoma pubmed","probabilities":0.9799733,"Title":"Mucins differently expressed in various ampullary adenocarcinomas","Abstract":"BACKGROUND: We investigated the occurrence and clinical significance of mucin expression in ampullary adenocarcinoma. METHODS: We retrospectively analyzed clinical, pathological, and survival data from 74 ampullary adenocarcinoma patients who received radical operation from January 2004 to November 2006. RESULTS: The tumors were located in the lower end of the common bile duct (46%), papillary duodenum (42%), and ampullary duodenum (12%), and expressed MUC1 (72%), MUC2 (20%), MUC5AC (43%), and MUC6 (27%). Expression of MUC1 was associated with tumor differentiation (OR: 4.71, 95% CI: 1.26, 17.66, P = 0.021). Expression of MUC5AC was associated with age (OR: 1.07, 95% CI: 1.11, 1.14, P = 0.026) and less vessel invasion(OR: 0.14, 95% CI: 0.03, 0.72, P = 0.019). The survival rates were not significantly different when patients had or had no expression of MUC1, MUC2, MUC5AC, or MUC6 in tumor. Patients with tumors positive for MUC5AC in the papillary duodenum had worse survival than those with tumors negative for MUC5AC (P = 0.044). CONCLUSIONS: Expression of MUC1 was high (72%) in ampullary adenocarcinoma, while expressions of MUC2, MUC5AC, and MUC6 were lower. Mucins are useful markers to diagnose and identify ampullary adenocarcinoma, particularly in determining the degree of malignancy of ampullary adenocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Mucins differently expressed in various ampullary adenocarcinomas BACKGROUND: We investigated the occurrence and clinical significance of mucin expression in ampullary adenocarcinoma. METHODS: We retrospectively analyzed clinical, pathological, and survival data from 74 ampullary adenocarcinoma patients who received radical operation from January 2004 to November 2006. RESULTS: The tumors were located in the lower end of the common bile duct (46%), papillary duodenum (42%), and ampullary duodenum (12%), and expressed MUC1 (72%), MUC2 (20%), MUC5AC (43%), and MUC6 (27%). Expression of MUC1 was associated with tumor differentiation (OR: 4.71, 95% CI: 1.26, 17.66, P = 0.021). Expression of MUC5AC was associated with age (OR: 1.07, 95% CI: 1.11, 1.14, P = 0.026) and less vessel invasion(OR: 0.14, 95% CI: 0.03, 0.72, P = 0.019). The survival rates were not significantly different when patients had or had no expression of MUC1, MUC2, MUC5AC, or MUC6 in tumor. Patients with tumors positive for MUC5AC in the papillary duodenum had worse survival than those with tumors negative for MUC5AC (P = 0.044). CONCLUSIONS: Expression of MUC1 was high (72%) in ampullary adenocarcinoma, while expressions of MUC2, MUC5AC, and MUC6 were lower. Mucins are useful markers to diagnose and identify ampullary adenocarcinoma, particularly in determining the degree of malignancy of ampullary adenocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"sumoylation p27kip1 via ranbp2 promotes cancer cell growth cholangiocarcinoma cell line qbc939 background cholangiocarcinoma one deadly disease poor 5 year survival poor response conventional therapies previously found p27kip1 nuclear cytoplasmic translocation confers proliferation potential cholangiocarcinoma cell line qbc939 process mediated crm 1 however post transcriptional regulation found process including sumoylation cholangiocarcinoma results study explored role sumoylation nuclear cytoplasmic translocation p27kip1 involvement qbc939 cells proliferation first identified k73 sumoylation site p27kip1 utilizing plasmid flag p27kip1 ha ranbp2 gst ranbp2 p27kip1 immunoprecipitation assay validated p27kip1 serve sumoylation target ranbp2 qbc939 furthermore confirmed crm 1 role promoting nuclear cytoplasmic translocation p27kip1 found ranbp2 function relies crm 1 however k73r mutated p27kip1 identified crm 1 ranbp2 p27kip1 translocation process suggesting sumoylation p27kip1 via k73 site necessary process ranbp2 crm 1 phenotypically overexpression either ranbp2 crm 1 partially rescue anti proliferative effect brought p27kip1 overexpression mts edu assay first time identified validated k73 sumoylation site p27kip1 critical ranbp2 crm 1 p27kip1 nuclear cytoplasmic translocation process conclusion taken together targeted inhibition sumoylation p27kip1 may serve potentially potent therapeutic target eradication cholangiocarcinoma development relapses stn","probabilities":0.9467213,"Title":"Sumoylation In P27Kip1 Via Ranbp2 Promotes Cancer Cell Growth In Cholangiocarcinoma Cell Line Qbc939","Abstract":"Background: Cholangiocarcinoma is one of the deadly disease with poor 5-year survival and poor response to conventional therapies. Previously, we found that p27kip1 nuclear-cytoplasmic translocation confers proliferation potential to cholangiocarcinoma cell line QBC939 and this process is mediated by crm-1. However, no other post-transcriptional regulation was found in this process including sumoylation in cholangiocarcinoma. \r\n\r\n Results: In this study, we explored the role of sumoylation in the nuclear-cytoplasmic translocation of p27kip1 and its involvement of QBC939 cells' proliferation. First, we identified K73 as the sumoylation site in p27kip1. By utilizing plasmid flag-p27kip1, HA-RanBP2, GST-RanBP2 and His-p27kip1 and immunoprecipitation assay, we validated that p27kip1 can serve as the sumoylation target of RanBP2 in QBC939. Furthermore, we confirmed crm-1's role in promoting nuclear-cytoplasmic translocation of p27kip1 and found that RanBP2's function relies on crm-1. However, K73R mutated p27kip1 can't be identified by crm-1 or RanBP2 in p27kip1 translocation process, suggesting sumoylation of p27kip1 via K73 site is necessary in this process by RanBP2 and crm-1. Phenotypically, the overexpression of either RanBP2 or crm-1 can partially rescue the anti-proliferative effect brought by p27kip1 overexpression in both the MTS and EdU assay. For the first time, we identified and validated the K73 sumoylation site in p27kip1, which is critical to RanBP2 and crm-1 in p27kip1 nuclear-cytoplasmic translocation process. \r\n\r\n Conclusion: Taken together, targeted inhibition of sumoylation of p27kip1 may serve as a potentially potent therapeutic target in the eradication of cholangiocarcinoma development and relapses.","Source":"STN","category":"ANIMAL","training_data":"Sumoylation In P27Kip1 Via Ranbp2 Promotes Cancer Cell Growth In Cholangiocarcinoma Cell Line Qbc939 Background: Cholangiocarcinoma is one of the deadly disease with poor 5-year survival and poor response to conventional therapies. Previously, we found that p27kip1 nuclear-cytoplasmic translocation confers proliferation potential to cholangiocarcinoma cell line QBC939 and this process is mediated by crm-1. However, no other post-transcriptional regulation was found in this process including sumoylation in cholangiocarcinoma. \r\n\r\n Results: In this study, we explored the role of sumoylation in the nuclear-cytoplasmic translocation of p27kip1 and its involvement of QBC939 cells' proliferation. First, we identified K73 as the sumoylation site in p27kip1. By utilizing plasmid flag-p27kip1, HA-RanBP2, GST-RanBP2 and His-p27kip1 and immunoprecipitation assay, we validated that p27kip1 can serve as the sumoylation target of RanBP2 in QBC939. Furthermore, we confirmed crm-1's role in promoting nuclear-cytoplasmic translocation of p27kip1 and found that RanBP2's function relies on crm-1. However, K73R mutated p27kip1 can't be identified by crm-1 or RanBP2 in p27kip1 translocation process, suggesting sumoylation of p27kip1 via K73 site is necessary in this process by RanBP2 and crm-1. Phenotypically, the overexpression of either RanBP2 or crm-1 can partially rescue the anti-proliferative effect brought by p27kip1 overexpression in both the MTS and EdU assay. For the first time, we identified and validated the K73 sumoylation site in p27kip1, which is critical to RanBP2 and crm-1 in p27kip1 nuclear-cytoplasmic translocation process. \r\n\r\n Conclusion: Taken together, targeted inhibition of sumoylation of p27kip1 may serve as a potentially potent therapeutic target in the eradication of cholangiocarcinoma development and relapses. STN","prediction_labels":"ANIMAL"},{"cleaned":"upregulation long non coding rna ccat2 indicates poor prognosis promotes proliferation metastasis intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma ihcc aggressive cancer poor survival rate second common type primary cancer hepatobiliary system present molecular mechanisms ihcc initiation progression remain unclear recent evidence indicated long non coding rnas lncrnas serve crucial role cancer development however functional role lncrnas ihcc investigated detail present study marked overexpression lncrna colon cancer associated transcript 2 ccat2 observed ihcc cell lines clinical specimens statistical analysis ihcc clinicopathological characteristics ccat2 expression data revealed high ccat2 expression levels correlated microvascular invasion differentiation grade tumor lymph node n metastasis m overall tnm stages ihcc p 0 05 kaplan meier analysis demonstrated ccat2 upregulation associated poor overall survival progression free survival ihcc furthermore high ccat2 expression identified independent risk factor ihcc poor prognosis univariate multivariate cox regression analyses role ccat2 promoting ihcc cell proliferation motility invasion confirmed vitro assays therefore ccat2 may promote ihcc progression metastasis may promising prognostic biomarker therapeutic target ihcc stn","probabilities":0.9467213,"Title":"Upregulation Of Long Non-Coding Rna Ccat2 Indicates A Poor Prognosis And Promotes Proliferation And Metastasis In Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (IHCC) is an aggressive cancer with a poor survival rate and is the second most common type of primary cancer of the hepatobiliary system. At present, the molecular mechanisms of IHCC initiation and progression remain unclear. Recent evidence has indicated that long non‑coding RNAs (lncRNAs) serve a crucial role in cancer development; however, the functional role of lncRNAs in IHCC has not been investigated in detail. In the present study, a marked overexpression of lncRNA colon cancer‑associated transcript 2 (CCAT2) was observed in IHCC cell lines and clinical specimens. Statistical analysis of IHCC clinicopathological characteristics and CCAT2 expression data revealed that high CCAT2 expression levels correlated with microvascular invasion, differentiation grade, tumor (T), lymph node (N), metastasis (M) and overall TNM stages of IHCC (P<0.05). Kaplan‑Meier analysis demonstrated that CCAT2 upregulation was associated with poor overall survival and progression‑free survival in IHCC. Furthermore, high CCAT2 expression was identified as an independent risk factor of IHCC poor prognosis in both univariate and multivariate Cox regression analyses. The role of CCAT2 in promoting IHCC cell proliferation, motility and invasion was further confirmed with in vitro assays. Therefore, CCAT2 may promote IHCC progression and metastasis, and may be a promising prognostic biomarker and therapeutic target in IHCC.","Source":"STN","category":"ANIMAL","training_data":"Upregulation Of Long Non-Coding Rna Ccat2 Indicates A Poor Prognosis And Promotes Proliferation And Metastasis In Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma (IHCC) is an aggressive cancer with a poor survival rate and is the second most common type of primary cancer of the hepatobiliary system. At present, the molecular mechanisms of IHCC initiation and progression remain unclear. Recent evidence has indicated that long non‑coding RNAs (lncRNAs) serve a crucial role in cancer development; however, the functional role of lncRNAs in IHCC has not been investigated in detail. In the present study, a marked overexpression of lncRNA colon cancer‑associated transcript 2 (CCAT2) was observed in IHCC cell lines and clinical specimens. Statistical analysis of IHCC clinicopathological characteristics and CCAT2 expression data revealed that high CCAT2 expression levels correlated with microvascular invasion, differentiation grade, tumor (T), lymph node (N), metastasis (M) and overall TNM stages of IHCC (P<0.05). Kaplan‑Meier analysis demonstrated that CCAT2 upregulation was associated with poor overall survival and progression‑free survival in IHCC. Furthermore, high CCAT2 expression was identified as an independent risk factor of IHCC poor prognosis in both univariate and multivariate Cox regression analyses. The role of CCAT2 in promoting IHCC cell proliferation, motility and invasion was further confirmed with in vitro assays. Therefore, CCAT2 may promote IHCC progression and metastasis, and may be a promising prognostic biomarker and therapeutic target in IHCC. STN","prediction_labels":"ANIMAL"},{"cleaned":"c flips l plays major role modulating survival immune escape mechanisms intrahepatic cholangiocarcinoma ihcca study primary human cell cultures ihcca deadly due aggressiveness late diagnosis treatment refractory nature recently established primary cell cultures specimens human mucin mixed ihcca subtypes aim study investigate role functional components fas fasl pathway ihcca dynamic interaction human immune cells methods fas fas l fadd c flips l bcl 2 pro caspase 8 expressions evaluated primary cultures human mucin mixed ihcca immunofluorescence western blot wb direct co cultures peripheral blood mononuclear cells pbmcs used analyze influ ence cca cell proliferation apoptosis evaluate apoptotic machinery downstream fas fasl pathway results mucin mixed ihcca cells constitutively express high levels fas fasl following direct co culture pbmcs expression fas fasl significantly increased 24 48 72 hours exposure p 0 05 time points significant increase percentage apop totic cd4 cd8 positive cells natural killer cd56 positive cells observed co cultures compared pbmcs cultured alone p 0 05 conversely ihcca subtypes showed increased cell proliferation co cultur ing pbmcs p 0 05 wb analysis revealed stable expression fadd either ihcca cells cultured alone co cultured pbmcs interestingly ihcca subtypes observed increased expression c flips l 24 hours co culture pbmcs 47 3 increase mucin ihcca 35 3 increase mixed ihcca vs cells cultured alone p 0 05 analysis showed strictly nuclear staining c flips l ih cca subtypes cultured alone whereas co cul ture pbmcs either nuclear cytoplasmic staining c flips l observed interestingly co cultures significant increase pro caspase 8 bcl 2 expression detected conclusion demonstrated co cul tured pbmcs human ihcca cells displayed enhanced expression fas fasl followed increase c flips l resulting proliferative anti apoptotic effects find ings indicate human ihcca c flips l represents key player modulation immune escape cell proliferation resistance apoptosis c flips l represent potential therapeutic target ihcca management google scholar","probabilities":0.9467213,"Title":"C-Flips/L Plays A Major Role In Modulating Survival And Immune Escape Mechanisms In Intrahepatic Cholangiocarcinoma (Ihcca): A Study On Primary Human Cell Cultures","Abstract":"IHCCA is very deadly due to its aggressiveness, late diagnosis and treatment refractory nature. We have recently established primary cell cultures from specimens of human mucin- and mixed-IHCCA subtypes. The aim of this study was to investigate the role of functional components of the Fas/FasL pathway in IHCCA and the dynamic interaction with human immune cells. Methods: Fas, Fas-L, FADD, c-FLIPS/L, Bcl-2 and pro-caspase 8 expressions were evaluated in primary cultures of human mucin- and mixed-IHCCA, by immunofluorescence (IF) and Western Blot (WB). Direct co-cultures with peripheral blood mononuclear cells (PBMCs) were used to analyze the influ-ence on CCA cell proliferation and apoptosis and, to evaluate the apoptotic machinery downstream the Fas/FasL pathway. Results: mucin- and mixed-IHCCA cells constitutively express high levels of Fas and FasL. Following direct co-culture with PBMCs, the expression of Fas and FasL significantly increased after 24, 48 and 72 hours of exposure (p< 0.05). At the same time points, a significant increase of the percentage of apop-totic CD4 and CD8 positive T-cells and Natural Killer CD56 positive cells were observed in the co-cultures as compared with PBMCs cultured alone (p< 0.05). Conversely, both IHCCA subtypes showed increased cell proliferation after co-cultur-ing with PBMCs (p< 0.05). WB analysis revealed a stable expression of FADD either in IHCCA cells cultured alone or co-cultured with PBMCs. Interestingly, in both IHCCA subtypes, we observed an increased expression of c-FLIPS/L 24 hours after co-culture with PBMCs (47±3% increase in mucin-IHCCA and 35±3% increase in mixed-IHCCA vs cells cultured alone, p< 0.05). IF analysis showed a strictly nuclear staining for c-FLIPS/L in both IH-CCA subtypes cultured alone, whereas after co-cul-ture with PBMCs, either nuclear or cytoplasmic staining for c-FLIPS/L was observed. Interestingly, in the same co-cultures, a significant increase of pro-caspase 8 and Bcl-2 expression was detected. In conclusion, we demonstrated that, when co-cul-tured with PBMCs, human IHCCA cells displayed an enhanced expression of Fas and FasL, followed by an increase in c-FLIPS/L, resulting in proliferative and anti-apoptotic effects. These find-ings indicate that, in human IHCCA, c-FLIPS/L represents a key player in the modulation of immune escape, cell proliferation and resistance against apoptosis. c-FLIPS/L could represent a potential therapeutic target for IHCCA management","Source":"Google Scholar","category":"ANIMAL","training_data":"C-Flips/L Plays A Major Role In Modulating Survival And Immune Escape Mechanisms In Intrahepatic Cholangiocarcinoma (Ihcca): A Study On Primary Human Cell Cultures IHCCA is very deadly due to its aggressiveness, late diagnosis and treatment refractory nature. We have recently established primary cell cultures from specimens of human mucin- and mixed-IHCCA subtypes. The aim of this study was to investigate the role of functional components of the Fas/FasL pathway in IHCCA and the dynamic interaction with human immune cells. Methods: Fas, Fas-L, FADD, c-FLIPS/L, Bcl-2 and pro-caspase 8 expressions were evaluated in primary cultures of human mucin- and mixed-IHCCA, by immunofluorescence (IF) and Western Blot (WB). Direct co-cultures with peripheral blood mononuclear cells (PBMCs) were used to analyze the influ-ence on CCA cell proliferation and apoptosis and, to evaluate the apoptotic machinery downstream the Fas/FasL pathway. Results: mucin- and mixed-IHCCA cells constitutively express high levels of Fas and FasL. Following direct co-culture with PBMCs, the expression of Fas and FasL significantly increased after 24, 48 and 72 hours of exposure (p< 0.05). At the same time points, a significant increase of the percentage of apop-totic CD4 and CD8 positive T-cells and Natural Killer CD56 positive cells were observed in the co-cultures as compared with PBMCs cultured alone (p< 0.05). Conversely, both IHCCA subtypes showed increased cell proliferation after co-cultur-ing with PBMCs (p< 0.05). WB analysis revealed a stable expression of FADD either in IHCCA cells cultured alone or co-cultured with PBMCs. Interestingly, in both IHCCA subtypes, we observed an increased expression of c-FLIPS/L 24 hours after co-culture with PBMCs (47±3% increase in mucin-IHCCA and 35±3% increase in mixed-IHCCA vs cells cultured alone, p< 0.05). IF analysis showed a strictly nuclear staining for c-FLIPS/L in both IH-CCA subtypes cultured alone, whereas after co-cul-ture with PBMCs, either nuclear or cytoplasmic staining for c-FLIPS/L was observed. Interestingly, in the same co-cultures, a significant increase of pro-caspase 8 and Bcl-2 expression was detected. In conclusion, we demonstrated that, when co-cul-tured with PBMCs, human IHCCA cells displayed an enhanced expression of Fas and FasL, followed by an increase in c-FLIPS/L, resulting in proliferative and anti-apoptotic effects. These find-ings indicate that, in human IHCCA, c-FLIPS/L represents a key player in the modulation of immune escape, cell proliferation and resistance against apoptosis. c-FLIPS/L could represent a potential therapeutic target for IHCCA management Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"incidence management outcome incidental gallbladder carcinoma analysis database swiss association laparoscopic thoracoscopic surgery background little known long term survival patients incidental gallbladder carcinoma igbc role radical resection disease discussed controversially literature present long term survival results re resection versus simple cholecystectomy database swiss association laparoscopic thoracoscopic surgery salts 1994 2004 methods eighty nine patients histologically confirmed carcinoma gallbladder identified 30 960 patients undergoing laparoscopic cholecystectomy sixty nine patients included study long term survival different stage comparison patients extended resection versus simple cholecystectomy calculated using log rank test time event data demonstrated kaplan meier curves results overall incidence igbc patients underwent laparoscopic cholecystectomy 0 28 89 30 960 fifty patients underwent simple cholecystectomy n 2 carcinoma situ cis n 2 pt1a n 10 pt1b n 23 pt2 n 8 pt3 n 5 pt4 whereas extended resection performed 19 cases n 2 pt1b n 11 pt2 n 6 pt3 comparison simple cholecystectomy versus extended re resection gallbladder bed regional lymph node resections showed significant benefit overall survival pt2 pt3 group p 0 05 pt1b group showed significant benefit overall survival p 0 34 conclusion igbc low incidence 0 28 present large study patients igbc comparing overall survival different histological findings observed significant benefit group pt2 pt3 therefore recommend extended resection gallbladder bed regional lymph nodes patient incidental histologically confirmed pt2 pt3 carcinoma gallbladder performance laparoscopic cholecystectomy patients pt1b stage recommendations given based study stn","probabilities":0.9799733,"Title":"Incidence Management And Outcome Of Incidental Gallbladder Carcinoma: Analysis Of The Database Of The Swiss Association Of Laparoscopic And Thoracoscopic Surgery","Abstract":"Background: Little is known about the long-term survival of patients with incidental gallbladder carcinoma (IGBC). The role of radical resection for this disease is discussed controversially in the literature. We present the long-term survival and the results of re-resection versus simple cholecystectomy of the database of the Swiss Association for Laparoscopic and Thoracoscopic Surgery (SALTS) from 1994 to 2004. \r\n\r\n Methods: Eighty-nine patients with histologically confirmed carcinoma of the gallbladder were identified out of 30,960 patients undergoing laparoscopic cholecystectomy. Sixty-nine patients were included in our study. Long-term survival by different T-stage and comparison of patients with extended resection versus simple cholecystectomy were calculated using the log-rank test. The time-to-event data are demonstrated by Kaplan-Meier curves. \r\n\r\n Results: The overall incidence of IGBC in patients who underwent laparoscopic cholecystectomy was 0.28% (89 of 30,960). Fifty patients underwent simple cholecystectomy [n = 2: carcinoma in situ (CIS); n = 2: pT1a; n = 10: pT1b; n = 23: pT2; n = 8: pT3; n = 5: pT4], whereas extended resection was performed in 19 cases (n = 2: pT1b; n = 11: pT2; n = 6: pT3). The comparison of simple cholecystectomy versus extended re-resection of the gallbladder bed and regional lymph node resections showed a significant benefit in overall survival for the pT2 and pT3 group (p < 0.05). The pT1b group showed no significant benefit in overall survival (p = 0.34). \r\n\r\n Conclusion: IGBC has a low incidence (0.28%). We present a large study of patients with IGBC, comparing the overall survival by different histological findings. We observed a significant benefit for the group with pT2 and pT3. Therefore we recommend extended resection of the gallbladder bed and the regional lymph nodes for patient with incidental histologically confirmed pT2 and pT3 carcinoma of the gallbladder after performance of laparoscopic cholecystectomy. For patients with pT1b stage no recommendations can be given based on this study.","Source":"STN","category":"HUMAN","training_data":"Incidence Management And Outcome Of Incidental Gallbladder Carcinoma: Analysis Of The Database Of The Swiss Association Of Laparoscopic And Thoracoscopic Surgery Background: Little is known about the long-term survival of patients with incidental gallbladder carcinoma (IGBC). The role of radical resection for this disease is discussed controversially in the literature. We present the long-term survival and the results of re-resection versus simple cholecystectomy of the database of the Swiss Association for Laparoscopic and Thoracoscopic Surgery (SALTS) from 1994 to 2004. \r\n\r\n Methods: Eighty-nine patients with histologically confirmed carcinoma of the gallbladder were identified out of 30,960 patients undergoing laparoscopic cholecystectomy. Sixty-nine patients were included in our study. Long-term survival by different T-stage and comparison of patients with extended resection versus simple cholecystectomy were calculated using the log-rank test. The time-to-event data are demonstrated by Kaplan-Meier curves. \r\n\r\n Results: The overall incidence of IGBC in patients who underwent laparoscopic cholecystectomy was 0.28% (89 of 30,960). Fifty patients underwent simple cholecystectomy [n = 2: carcinoma in situ (CIS); n = 2: pT1a; n = 10: pT1b; n = 23: pT2; n = 8: pT3; n = 5: pT4], whereas extended resection was performed in 19 cases (n = 2: pT1b; n = 11: pT2; n = 6: pT3). The comparison of simple cholecystectomy versus extended re-resection of the gallbladder bed and regional lymph node resections showed a significant benefit in overall survival for the pT2 and pT3 group (p < 0.05). The pT1b group showed no significant benefit in overall survival (p = 0.34). \r\n\r\n Conclusion: IGBC has a low incidence (0.28%). We present a large study of patients with IGBC, comparing the overall survival by different histological findings. We observed a significant benefit for the group with pT2 and pT3. Therefore we recommend extended resection of the gallbladder bed and the regional lymph nodes for patient with incidental histologically confirmed pT2 and pT3 carcinoma of the gallbladder after performance of laparoscopic cholecystectomy. For patients with pT1b stage no recommendations can be given based on this study. STN","prediction_labels":"HUMAN"},{"cleaned":"role adjuvant chemoradiotherapy pancreatobiliary versus intestinal subtypes ampullary cancers background ampullarycancerstraditionallyhavehadmorefavorableoutcomesthantumors pancreatic head current literature suggests use adjuvant therapies may benefit populations certain high risk features whether adjuvant therapies specific histologicalsubtypesinfluenceoutcomeshasremainedunanswered methods weretrospectively analyzed 44 patients 1996 2010 dedicated cancer center pathological stage histologicalsubtypes pancreatobiliary pb versusintestinal int marginstatus lymphovascular invasion lvi perineural invasion pni overall survival os disease free survival dfs analyzed kaplan meier methods used estimate survival differences assessed using log rank wilcoxon tests looked differences survival histological subtype within adjuvant chemoradiotherapy acrt surgery subgroups accounting stage results 44 patients 15 male 29 female average age 64 twenty patients underwent classic pancreatoduodenectomy pd 24 pylorus preserving pd nine percent patients pathologic stage ia 18 ib 23 iia 36 iib 14 iii upon review senior pathologist 25 patients found pb histology 18 int 1 mixed lvi pni found 32 25 neoadjuvant chemoradiation given 3 patients acrt given 15 patients adjuvant chemotherapy 5 adjuvant radiation 2 nineteen patients underwent surgical resection modality os 2 years 75 pb compared 70 int 5 years 63 46 respectively p 0 11 within acrt group pb patients improved os int p 0 027 dfs 2 years 63 pb compared 59 int 5 years 58 28 p 0 05 within acrt group pb patients improved dfs int p 0 01 choice gemcitabine versus 5 fluorouracil 5fu basedregimensdidnotreachstatisticalsignificancewhencomparingsurvival comparing stage iibs showed improved os dfs iias p 0 05 0 006 within iibs acrt improvedosirrespectiveofhistology p 0 010 stratifyingpbpatientswithintheiibgroup os dfs improved compared intestinal variant acrt given p 0 03 0 02 conclusions use acrt patients ampullary tumors may important survival histologic type larger studies needed distinguish effects adjuvant therapy histologic type google scholar","probabilities":0.9799733,"Title":"The Role Of Adjuvant Chemoradiotherapy In Pancreatobiliary Versus Intestinal Subtypes Of Ampullary Cancers","Abstract":"Background:Ampullarycancerstraditionallyhavehadmorefavorableoutcomesthantumors in the pancreatic head. Current literature suggests the use of adjuvant therapies may be of benefit in populations with certain high risk features. Whether adjuvant therapies in specific histologicalsubtypesinfluenceoutcomeshasremainedunanswered.Methods:Weretrospectively analyzed 44 patients from 1996-2010 at a dedicated cancer center. Pathological stage, histologicalsubtypes(pancreatobiliary(PB)versusintestinal(INT)),marginstatus,lymphovascular invasion(LVI), perineural invasion(PNI), overall survival(OS) and disease free survival(DFS) were analyzed. Kaplan-Meier methods were used to estimate survival, and differences were assessed using the log rank and Wilcoxon tests. We looked at differences in survival by histological subtype within the adjuvant chemoradiotherapy(ACRT) and surgery only subgroups, accounting for stage. Results: Of 44 patients, 15 were male and 29 female; average age was 64. Twenty patients underwent a classic pancreatoduodenectomy(PD), and 24 a pylorus preserving PD. Nine percent of patients were pathologic stage IA, 18% IB, 23% IIA, 36% IIB, and 14% III. Upon review by a senior pathologist, 25 patients were found to have a PB histology, 18 INT, and 1 mixed. LVI and PNI were found in 32% and 25%. Neoadjuvant chemoradiation was given to 3 patients. ACRT was given to 15 patients, adjuvant chemotherapy to 5, and adjuvant radiation to 2. Nineteen patients underwent surgical resection with no other modality. OS at 2 years was 75% for PB compared to 70% for INT; at 5 years, 63% and 46%, respectively(p=0.11). Within the ACRT group, the PB patients had improved OS than INT(p=0.027). DFS at 2 years was 63% for PB compared to 59% for INT; at 5 years, 58% and 28%(p=0.05). Within the ACRT group, the PB patients had improved DFS than INT(p=0.01). The choice between gemcitabine versus 5 fluorouracil (5FU)basedregimensdidnotreachstatisticalsignificancewhencomparingsurvival.Comparing stage, IIBs showed improved OS and DFS than IIAs(p=0.05,0.006). Within IIBs, ACRT improvedOSirrespectiveofhistology(p=0.010).StratifyingPBpatientswithintheIIBgroup, OS and DFS were improved compared to its intestinal variant when ACRT was given(p= 0.03,0.02). Conclusions: The use of ACRT in patients with ampullary tumors may be more important for survival than histologic type. Larger studies will be needed to distinguish the effects of adjuvant therapy from those on histologic type","Source":"Google Scholar","category":"HUMAN","training_data":"The Role Of Adjuvant Chemoradiotherapy In Pancreatobiliary Versus Intestinal Subtypes Of Ampullary Cancers Background:Ampullarycancerstraditionallyhavehadmorefavorableoutcomesthantumors in the pancreatic head. Current literature suggests the use of adjuvant therapies may be of benefit in populations with certain high risk features. Whether adjuvant therapies in specific histologicalsubtypesinfluenceoutcomeshasremainedunanswered.Methods:Weretrospectively analyzed 44 patients from 1996-2010 at a dedicated cancer center. Pathological stage, histologicalsubtypes(pancreatobiliary(PB)versusintestinal(INT)),marginstatus,lymphovascular invasion(LVI), perineural invasion(PNI), overall survival(OS) and disease free survival(DFS) were analyzed. Kaplan-Meier methods were used to estimate survival, and differences were assessed using the log rank and Wilcoxon tests. We looked at differences in survival by histological subtype within the adjuvant chemoradiotherapy(ACRT) and surgery only subgroups, accounting for stage. Results: Of 44 patients, 15 were male and 29 female; average age was 64. Twenty patients underwent a classic pancreatoduodenectomy(PD), and 24 a pylorus preserving PD. Nine percent of patients were pathologic stage IA, 18% IB, 23% IIA, 36% IIB, and 14% III. Upon review by a senior pathologist, 25 patients were found to have a PB histology, 18 INT, and 1 mixed. LVI and PNI were found in 32% and 25%. Neoadjuvant chemoradiation was given to 3 patients. ACRT was given to 15 patients, adjuvant chemotherapy to 5, and adjuvant radiation to 2. Nineteen patients underwent surgical resection with no other modality. OS at 2 years was 75% for PB compared to 70% for INT; at 5 years, 63% and 46%, respectively(p=0.11). Within the ACRT group, the PB patients had improved OS than INT(p=0.027). DFS at 2 years was 63% for PB compared to 59% for INT; at 5 years, 58% and 28%(p=0.05). Within the ACRT group, the PB patients had improved DFS than INT(p=0.01). The choice between gemcitabine versus 5 fluorouracil (5FU)basedregimensdidnotreachstatisticalsignificancewhencomparingsurvival.Comparing stage, IIBs showed improved OS and DFS than IIAs(p=0.05,0.006). Within IIBs, ACRT improvedOSirrespectiveofhistology(p=0.010).StratifyingPBpatientswithintheIIBgroup, OS and DFS were improved compared to its intestinal variant when ACRT was given(p= 0.03,0.02). Conclusions: The use of ACRT in patients with ampullary tumors may be more important for survival than histologic type. Larger studies will be needed to distinguish the effects of adjuvant therapy from those on histologic type Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"predictive index tumor recurrence liver transplantation locally advanced intrahepatic hilar cholangiocarcinoma background current criteria orthotopic liver transplantation olt cholangiocarcinoma cca remain restricted early stage small hilar tumors excluding patients locally advanced intrahepatic hilar cca potential cure present study undertaken define prognostic scoring system risk stratification patients intrahepatic hilar cca might benefit olt allow expansion current olt criteria study design conducted retrospective review 40 patients underwent olt locally advanced intrahepatic hilar cca center february 1985 june 2010 median follow 3 years independent risk factors tumor recurrence olt identified using cox model assigned risk score points points summed assigned predictive index categories 0 3 low risk 4 7 intermediate risk 8 15 high risk results seven multivariate factors predictive tumor recurrence included multifocal tumor perineural invasion infiltrative growth pattern lack neoadjuvant adjuvant therapy history primary sclerosing cholangitis hilar tumors lymphovascular invasion 5 year tumor recurrence free patient survival significantly higher low risk 78 compared intermediate 19 high risk 0 groups p 0 001 survival benefit also seen intermediate compared high risk groups conclusions model highly predictive long term outcomes olt locally advanced intrahepatic hilar cca applied clinically risk stratification patients considered olt long term disease recurrence free survival excellent low risk acceptable intermediate risk groups justifying expansion liver transplant criteria treatment challenging malignancy pubmed","probabilities":0.9799733,"Title":"Predictive index for tumor recurrence after liver transplantation for locally advanced intrahepatic and hilar cholangiocarcinoma","Abstract":"BACKGROUND: Current criteria for orthotopic liver transplantation (OLT) for cholangiocarcinoma (CCA) remain restricted to early stage and small hilar tumors, excluding patients with locally advanced intrahepatic and hilar CCA for potential cure. The present study was undertaken to define a prognostic scoring system for risk stratification of patients with intrahepatic and hilar CCA who might benefit from OLT and to allow expansion of current OLT criteria. STUDY DESIGN: We conducted a retrospective review of 40 patients who underwent OLT for locally advanced intrahepatic and hilar CCA at our center between February 1985 and June 2010. Median follow-up was 3 years. Independent risk factors for tumor recurrence after OLT were identified using the Cox model and were assigned risk score points. Points were summed and assigned to predictive index categories: 0 to 3 for low risk, 4 to 7 for intermediate risk, and 8 to 15 for high risk. RESULTS: Seven multivariate factors predictive for tumor recurrence included multifocal tumor, perineural invasion, infiltrative growth pattern, lack of neoadjuvant and adjuvant therapy, history of primary sclerosing cholangitis, hilar tumors, and lymphovascular invasion. The 5-year tumor recurrence-free patient survival was significantly higher in low-risk (78%) compared with intermediate- (19%) and high-risk (0%) groups (p < 0.001); survival benefit was also seen in intermediate- compared with high-risk groups. CONCLUSIONS: This model was highly predictive of long-term outcomes after OLT for locally advanced intrahepatic and hilar CCA and can be applied clinically for risk stratification of patients considered for OLT. Long-term disease recurrence-free survival was excellent in low-risk and acceptable in intermediate-risk groups, justifying the expansion of liver transplant criteria for treatment of this challenging malignancy.","Source":"PubMed","category":"HUMAN","training_data":"Predictive index for tumor recurrence after liver transplantation for locally advanced intrahepatic and hilar cholangiocarcinoma BACKGROUND: Current criteria for orthotopic liver transplantation (OLT) for cholangiocarcinoma (CCA) remain restricted to early stage and small hilar tumors, excluding patients with locally advanced intrahepatic and hilar CCA for potential cure. The present study was undertaken to define a prognostic scoring system for risk stratification of patients with intrahepatic and hilar CCA who might benefit from OLT and to allow expansion of current OLT criteria. STUDY DESIGN: We conducted a retrospective review of 40 patients who underwent OLT for locally advanced intrahepatic and hilar CCA at our center between February 1985 and June 2010. Median follow-up was 3 years. Independent risk factors for tumor recurrence after OLT were identified using the Cox model and were assigned risk score points. Points were summed and assigned to predictive index categories: 0 to 3 for low risk, 4 to 7 for intermediate risk, and 8 to 15 for high risk. RESULTS: Seven multivariate factors predictive for tumor recurrence included multifocal tumor, perineural invasion, infiltrative growth pattern, lack of neoadjuvant and adjuvant therapy, history of primary sclerosing cholangitis, hilar tumors, and lymphovascular invasion. The 5-year tumor recurrence-free patient survival was significantly higher in low-risk (78%) compared with intermediate- (19%) and high-risk (0%) groups (p < 0.001); survival benefit was also seen in intermediate- compared with high-risk groups. CONCLUSIONS: This model was highly predictive of long-term outcomes after OLT for locally advanced intrahepatic and hilar CCA and can be applied clinically for risk stratification of patients considered for OLT. Long-term disease recurrence-free survival was excellent in low-risk and acceptable in intermediate-risk groups, justifying the expansion of liver transplant criteria for treatment of this challenging malignancy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"chemoradiotherapy initially unresectable locally advanced cholangiocarcinoma objective surgical resection available treatment achieving long term survival cholangiocarcinoma purpose study elucidate utility chemoradiotherapy initially unresectable locally advanced cholangiocarcinoma methods unresectable locally advanced cholangiocarcinoma defined radical surgery achieved even aggressive surgical procedure fifteen candidates 7 intrahepatic cholangiocarcinomas 8 hilar cholangiocarcinomas underwent chemoradiotherapy fourteen 15 patients received oral 1 chemotherapy radiotherapy administered 50 gy patient chemoradiotherapy resectability cholangiocarcinoma reexamined results 15 patients initially unresectable locally advanced cholangiocarcinoma 11 73 3 judged resectable cholangiocarcinoma chemoradiotherapy received radical hepatectomy r0 resection 9 patients among 11 patients underwent surgical resection 4 recurrence free survival median survival time mst 37 months overall 1 2 5 year survival rates 80 8 70 7 23 6 respectively among 4 patients unable receive surgery 3 died primary disease mst 10 months overall 1 2 year survival rates 37 5 0 respectively patients received radical surgery significantly longer survival time unable receive surgery p 0 027 conclusions chemoradiotherapy allowed patients initially unresectable locally advanced cholangiocarcinomas reclassified surgical candidates substantial proportion chemoradiotherapy might one treatment options similarly advanced cholangiocarcinomas stn","probabilities":0.9799733,"Title":"Chemoradiotherapy For Initially Unresectable Locally Advanced Cholangiocarcinoma","Abstract":"Objective: Surgical resection is the only available treatment for achieving long-term survival in cholangiocarcinoma. The purpose of this study is to elucidate the utility of chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. \r\n\r\n Methods: Unresectable locally advanced cholangiocarcinoma was defined as those in which radical surgery could not be achieved even with aggressive surgical procedure. Fifteen candidates (7 intrahepatic cholangiocarcinomas and 8 hilar cholangiocarcinomas) underwent chemoradiotherapy. Fourteen of the 15 patients received oral S-1 chemotherapy. Radiotherapy was administered with 50 Gy for each patient. After chemoradiotherapy, the resectability of each cholangiocarcinoma was reexamined. \r\n\r\n Results: Of the 15 patients with initially unresectable locally advanced cholangiocarcinoma, 11 (73.3%) were judged to have resectable cholangiocarcinoma after chemoradiotherapy, and received radical hepatectomy (R0 resection in 9 patients). Among the 11 patients who underwent surgical resection, 4 had recurrence-free survival and the median survival time (MST) was 37 months. The overall 1-, 2-, and 5-year survival rates were 80.8, 70.7 and 23.6%, respectively. Among the 4 patients who were unable to receive surgery, 3 died of the primary disease and the MST was 10 months. The overall 1- and 2-year survival rates were 37.5 and 0%, respectively. Patients who received radical surgery had significantly longer survival time than those who were unable to receive surgery (p = 0.027). \r\n\r\n Conclusions: Chemoradiotherapy allowed patients with initially unresectable locally advanced cholangiocarcinomas to be reclassified as surgical candidates in a substantial proportion. Chemoradiotherapy might be one of the treatment options for similarly advanced cholangiocarcinomas.","Source":"STN","category":"HUMAN","training_data":"Chemoradiotherapy For Initially Unresectable Locally Advanced Cholangiocarcinoma Objective: Surgical resection is the only available treatment for achieving long-term survival in cholangiocarcinoma. The purpose of this study is to elucidate the utility of chemoradiotherapy for initially unresectable locally advanced cholangiocarcinoma. \r\n\r\n Methods: Unresectable locally advanced cholangiocarcinoma was defined as those in which radical surgery could not be achieved even with aggressive surgical procedure. Fifteen candidates (7 intrahepatic cholangiocarcinomas and 8 hilar cholangiocarcinomas) underwent chemoradiotherapy. Fourteen of the 15 patients received oral S-1 chemotherapy. Radiotherapy was administered with 50 Gy for each patient. After chemoradiotherapy, the resectability of each cholangiocarcinoma was reexamined. \r\n\r\n Results: Of the 15 patients with initially unresectable locally advanced cholangiocarcinoma, 11 (73.3%) were judged to have resectable cholangiocarcinoma after chemoradiotherapy, and received radical hepatectomy (R0 resection in 9 patients). Among the 11 patients who underwent surgical resection, 4 had recurrence-free survival and the median survival time (MST) was 37 months. The overall 1-, 2-, and 5-year survival rates were 80.8, 70.7 and 23.6%, respectively. Among the 4 patients who were unable to receive surgery, 3 died of the primary disease and the MST was 10 months. The overall 1- and 2-year survival rates were 37.5 and 0%, respectively. Patients who received radical surgery had significantly longer survival time than those who were unable to receive surgery (p = 0.027). \r\n\r\n Conclusions: Chemoradiotherapy allowed patients with initially unresectable locally advanced cholangiocarcinomas to be reclassified as surgical candidates in a substantial proportion. Chemoradiotherapy might be one of the treatment options for similarly advanced cholangiocarcinomas. STN","prediction_labels":"HUMAN"},{"cleaned":"role caudate lobectomy type iiia iiib hilar cholangiocarcinoma 15 year experience tertiary institution background concomitant liver resection type iii hilar cholangiocarcinoma improve r0 resection rate long term outcome present study examine specific role caudate lobectomy liver resection type iii iii b hilar cholangiocarcinoma prognostic factors survival group patients methods reviewed patients type iii iii b hilar cholangiocarcinoma underwent liver resection samsung medical center january 1995 july 2010 patients divided without caudate lobectomy cl log rank test cox regression analysis employed investigate prognostic factors survival results 127 patients cohort 57 without cl 44 9 70 cl 55 1 demographics symptoms presentation comparable median preoperative bilirubin level significantly higher group undergoing cl p 0 017 patients cl significantly better overall survival os cl 64 0 months vs without cl 34 6 months p 0 010 disease free survival dfs cl 40 5 months vs without cl 27 0 months p 0 031 multivariate analysis showed presence symptoms p 0 025 positive lymph node ln metastasis p 0 001 negative prognostic factors os furthermore multivariate analysis dfs found caudate lobectomy p 0 016 positive ln metastasis p 0 001 positive negative prognostic factors respectively conclusions caudate lobectomy contributed improvement dfs os type iii hilar cholangiocarcinoma prognostic factors include positive ln metastasis presence symptoms google scholar","probabilities":0.9799733,"Title":"The Role Of Caudate Lobectomy In Type Iiia & Iiib Hilar Cholangiocarcinoma: A 15-Year Experience In A Tertiary Institution","Abstract":"Background: Concomitant liver resection for type III hilar cholangiocarcinoma could improve the R0 resection rate and long-term outcome. In the present study, we examine the specific role of caudate lobectomy in liver resection for type III(A) and III(B) hilar cholangiocarcinoma and the prognostic factors for survival in this group of patients. \nMethods: We reviewed all patients with type III(A) and III(B) hilar cholangiocarcinoma who underwent liver resection in Samsung Medical Center from January 1995 to July 2010. Patients were divided into those with and without caudate lobectomy (CL). The log rank test and Cox regression analysis were employed to investigate for prognostic factors of survival. \nResults: There were 127 patients in this cohort, 57 without CL (44.9%) and 70 with CL (55.1%). The demographics and symptoms of presentation were comparable. The median preoperative bilirubin level was significantly higher in the group undergoing CL (p = 0.017). Patients with CL had a significantly better overall survival (OS) (CL: 64.0 months vs without CL: 34.6 months) (p = 0.010) and disease-free survival (DFS) (CL: 40.5 months vs without CL: 27.0 months) (p = 0.031). Multivariate analysis showed that presence of symptoms (p = 0.025) and positive lymph node (LN) metastasis (p < 0.001) were negative prognostic factors for OS. Furthermore, multivariate analysis for DFS found that caudate lobectomy (p = 0.016) and positive LN metastasis (p = 0.001) were positive and negative prognostic factors, respectively. \nConclusions: Caudate lobectomy contributed to improvement of DFS and OS in type III hilar cholangiocarcinoma. Other prognostic factors include positive LN metastasis and presence of symptoms.","Source":"Google Scholar","category":"HUMAN","training_data":"The Role Of Caudate Lobectomy In Type Iiia & Iiib Hilar Cholangiocarcinoma: A 15-Year Experience In A Tertiary Institution Background: Concomitant liver resection for type III hilar cholangiocarcinoma could improve the R0 resection rate and long-term outcome. In the present study, we examine the specific role of caudate lobectomy in liver resection for type III(A) and III(B) hilar cholangiocarcinoma and the prognostic factors for survival in this group of patients. \nMethods: We reviewed all patients with type III(A) and III(B) hilar cholangiocarcinoma who underwent liver resection in Samsung Medical Center from January 1995 to July 2010. Patients were divided into those with and without caudate lobectomy (CL). The log rank test and Cox regression analysis were employed to investigate for prognostic factors of survival. \nResults: There were 127 patients in this cohort, 57 without CL (44.9%) and 70 with CL (55.1%). The demographics and symptoms of presentation were comparable. The median preoperative bilirubin level was significantly higher in the group undergoing CL (p = 0.017). Patients with CL had a significantly better overall survival (OS) (CL: 64.0 months vs without CL: 34.6 months) (p = 0.010) and disease-free survival (DFS) (CL: 40.5 months vs without CL: 27.0 months) (p = 0.031). Multivariate analysis showed that presence of symptoms (p = 0.025) and positive lymph node (LN) metastasis (p < 0.001) were negative prognostic factors for OS. Furthermore, multivariate analysis for DFS found that caudate lobectomy (p = 0.016) and positive LN metastasis (p = 0.001) were positive and negative prognostic factors, respectively. \nConclusions: Caudate lobectomy contributed to improvement of DFS and OS in type III hilar cholangiocarcinoma. Other prognostic factors include positive LN metastasis and presence of symptoms. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"low expression arid1a correlates poor prognosis intrahepatic cholangiocarcinoma aim investigate relationship arid1a expression clinicopathologic parameters well prognostic value patients intrahepatic cholangiocarcinoma ihcc methods assessed arid1a protein mrna expression ihcc tissues paracarcinomatous pc tissues 57 patients ihcc using western blot quantitative real time reverse transcription polymerase chain reaction respectively used fisher exact 2 tests analyze relationships clinicopathological parameters arid1a expression kaplan meier method cox regression used analyze survival results mean arid1a protein level ihcc tissues 1 16 0 36 relative units ru significantly lower pc tissues 1 26 0 21 ru p 0 01 nl tissues 1 11 0 31 p 0 001 mean arid1a mrna level ihcc tissues 1 20 0 18 also lower pc tissues 1 27 0 15 p 0 001 normal liver tissues 1 15 0 34 p 0 001 low arid1a expression significantly associated tumor nodules vein invasion recurrence median overall survival os disease free survival dfs low arid1a expression group 15 0 7 0 mo respectively significantly shorter high arid1a expression group 25 0 22 0 mo os p 0 01 dfs p 0 001 respectively low arid1a expression significantly associated worse os hr 3 967 95 ci 1 299 12 118 p 0 016 multivariate analyses conclusion low expression arid1a associated poor prognosis patients ihcc thus may potential prognostic biomarker candidate ihcc pubmed","probabilities":0.88235295,"Title":"Low expression of ARID1A correlates with poor prognosis in intrahepatic cholangiocarcinoma","Abstract":"AIM: To investigate the relationship between ARID1A expression and clinicopathologic parameters, as well as its prognostic value, for patients with intrahepatic cholangiocarcinoma (IHCC). METHODS: We assessed ARID1A protein and mRNA expression in IHCC tissues and paracarcinomatous (PC) tissues from 57 patients with IHCC using western blot and quantitative real-time reverse transcription polymerase chain reaction, respectively. We used Fisher's exact and χ(2) tests to analyze relationships between clinicopathological parameters and ARID1A expression. The Kaplan-Meier method and Cox regression were used to analyze survival. RESULTS: The mean ARID1A protein level in IHCC tissues was 1.16 ± 0.36 relative units (RU), which was significantly lower than that in PC tissues (1.26 ± 0.21 RU, P < 0.01) and NL tissues (1.11 ± 0.31, P < 0.001). The mean ARID1A mRNA level in IHCC tissues (1.20 ± 0.18) was also lower than that in PC tissues (1.27 ± 0.15, P < 0.001) and normal liver tissues (1.15 ± 0.34, P < 0.001). Low ARID1A expression was significantly associated with tumor nodules, vein invasion, and recurrence. Median overall survival (OS) and disease-free survival (DFS) for the low ARID1A expression group was 15.0 and 7.0 mo, respectively, which were significantly shorter than those for the high ARID1A expression group at 25.0 and 22.0 mo (OS: P < 0.01; DFS: P < 0.001), respectively. Low ARID1A expression was significantly associated with worse OS (HR = 3.967, 95%CI: 1.299-12.118, P = 0.016) in multivariate analyses. CONCLUSION: Low expression of ARID1A is associated with poor prognosis in patients with IHCC, and thus may be a potential prognostic biomarker candidate in IHCC.","Source":"PubMed","category":"HUMAN","training_data":"Low expression of ARID1A correlates with poor prognosis in intrahepatic cholangiocarcinoma AIM: To investigate the relationship between ARID1A expression and clinicopathologic parameters, as well as its prognostic value, for patients with intrahepatic cholangiocarcinoma (IHCC). METHODS: We assessed ARID1A protein and mRNA expression in IHCC tissues and paracarcinomatous (PC) tissues from 57 patients with IHCC using western blot and quantitative real-time reverse transcription polymerase chain reaction, respectively. We used Fisher's exact and χ(2) tests to analyze relationships between clinicopathological parameters and ARID1A expression. The Kaplan-Meier method and Cox regression were used to analyze survival. RESULTS: The mean ARID1A protein level in IHCC tissues was 1.16 ± 0.36 relative units (RU), which was significantly lower than that in PC tissues (1.26 ± 0.21 RU, P < 0.01) and NL tissues (1.11 ± 0.31, P < 0.001). The mean ARID1A mRNA level in IHCC tissues (1.20 ± 0.18) was also lower than that in PC tissues (1.27 ± 0.15, P < 0.001) and normal liver tissues (1.15 ± 0.34, P < 0.001). Low ARID1A expression was significantly associated with tumor nodules, vein invasion, and recurrence. Median overall survival (OS) and disease-free survival (DFS) for the low ARID1A expression group was 15.0 and 7.0 mo, respectively, which were significantly shorter than those for the high ARID1A expression group at 25.0 and 22.0 mo (OS: P < 0.01; DFS: P < 0.001), respectively. Low ARID1A expression was significantly associated with worse OS (HR = 3.967, 95%CI: 1.299-12.118, P = 0.016) in multivariate analyses. CONCLUSION: Low expression of ARID1A is associated with poor prognosis in patients with IHCC, and thus may be a potential prognostic biomarker candidate in IHCC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"evaluation utility staging systems pronosticmodels independent pre operative post resectional variables upon survival characteristics resected peri hilar cholangiocarcinoma patients abstract aims surgical resection potentially curative treatment cholangiocarcinoma patients multiple prognostic systems utilised provide prognostication patient guide management strategies post resection objective study evaluate independent prognostic variables prognostic models modern single centre resectional cohort method patients diagnosed hilar cholangiocarcinoma referred supra regional tertiary referral centre february 2009 february 2016 retrospectively analysed prospectively held database linked hospital episode statistics somerset cancer registry data results two hundred one patients assessed suitability surgery eighty three 48 2 patients considered potentially resectable disease underwent surgical assessment resectability multivariate analysis demonstrated pre operative serum ca 19 9 p 0 007 radiological arterial involvement p 0 005 amc nomogram score p 0 032 retained significance association overall survival os nodal status p 0 007 tumour grading p 0 001 retained significance association os recurrence free survival augmented multivariate model outperformed prognostic systems os concordance index 0 71 conclusion amc nomogram improved prognostic capability compared staging systems externally validated first time cohort augmentation amc nomogram addition significant independent pre operative covariates cohort produced significantly improved prognostication model os google scholar","probabilities":0.9799733,"Title":"Evaluation Of The Utility Of Staging Systems Pronosticmodels And Independent Pre-Operative And Post-Resectional Variables Upon Survival Characteristics For Resected Peri-Hilar Cholangiocarcinoma Patients","Abstract":"Abstract\nAims:\nSurgical resection is the only potentially curative treatment for cholangiocarcinoma patients. Multiple prognostic systems have been utilised to provide prognostication for the patient and to guide management strategies post-resection. The objective of this study was to evaluate independent prognostic variables and prognostic models in a modern single-centre resectional cohort. \nMethod:\nPatients diagnosed with hilar cholangiocarcinoma, referred to a supra-regional tertiary referral centre between February 2009 and February 2016, were retrospectively analysed from a prospectively held database linked to Hospital Episode Statistics and Somerset Cancer Registry data.\nResults:\nTwo-hundred and one patients were assessed for suitability for surgery. Eighty-three (48∙2 %) patients considered to have potentially resectable disease underwent surgical assessment of resectability. Multivariate analysis demonstrated pre-operative Serum CA 19-9 (p= 0.007), radiological arterial involvement (p= 0.005) and AMC Nomogram score (p= 0.032) retained significance in association with overall survival (OS). Nodal status (p= 0.007) and tumour grading (p= 0.001) retained significance in association with both OS and recurrence-free survival. An augmented multivariate model outperformed the other prognostic systems for OS (Concordance Index= 0.71).\nConclusion: \nThe AMC nomogram has an improved prognostic capability, compared to the other staging systems, and has been externally validated for the first time in this cohort. Augmentation of the AMC nomogram by addition of significant independent pre-operative covariates from this cohort produced a significantly improved prognostication model for OS.","Source":"Google Scholar","category":"HUMAN","training_data":"Evaluation Of The Utility Of Staging Systems Pronosticmodels And Independent Pre-Operative And Post-Resectional Variables Upon Survival Characteristics For Resected Peri-Hilar Cholangiocarcinoma Patients Abstract\nAims:\nSurgical resection is the only potentially curative treatment for cholangiocarcinoma patients. Multiple prognostic systems have been utilised to provide prognostication for the patient and to guide management strategies post-resection. The objective of this study was to evaluate independent prognostic variables and prognostic models in a modern single-centre resectional cohort. \nMethod:\nPatients diagnosed with hilar cholangiocarcinoma, referred to a supra-regional tertiary referral centre between February 2009 and February 2016, were retrospectively analysed from a prospectively held database linked to Hospital Episode Statistics and Somerset Cancer Registry data.\nResults:\nTwo-hundred and one patients were assessed for suitability for surgery. Eighty-three (48∙2 %) patients considered to have potentially resectable disease underwent surgical assessment of resectability. Multivariate analysis demonstrated pre-operative Serum CA 19-9 (p= 0.007), radiological arterial involvement (p= 0.005) and AMC Nomogram score (p= 0.032) retained significance in association with overall survival (OS). Nodal status (p= 0.007) and tumour grading (p= 0.001) retained significance in association with both OS and recurrence-free survival. An augmented multivariate model outperformed the other prognostic systems for OS (Concordance Index= 0.71).\nConclusion: \nThe AMC nomogram has an improved prognostic capability, compared to the other staging systems, and has been externally validated for the first time in this cohort. Augmentation of the AMC nomogram by addition of significant independent pre-operative covariates from this cohort produced a significantly improved prognostication model for OS. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"postoperative morbidity predictor early recurrence poor survival following major hepatectomy advanced perihilar cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Postoperative Morbidity As Predictor Of Early Recurrence And Poor Survival Following Major Hepatectomy For Advanced Perihilar Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Postoperative Morbidity As Predictor Of Early Recurrence And Poor Survival Following Major Hepatectomy For Advanced Perihilar Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"folfiri plus bevacizumab second line therapy metastatic intrahepatic cholangiocarcinoma aim evaluate efficacy tolerance folfiri plus bevacizumab treatment outcome second line treatment metastatic intrahepatic cholangiocarcinoma methods thirteen consecutive patients metastatic intrahepatic cholangiocarcinoma refractory first line therapy consisting gemcitabine plus oxaliplatin based first line chemotherapy given intravenously via intra arterial infusion treated folfiri irinotecan 180 mg m v 90 min concurrently folinic acid 400 mg m v 120 min followed fluorouracil 400 mg m v bolus fluorouracil 2400 mg m intravenous infusion 46 h bevacizumab 5 mg kg every 2 wk tumor response evaluated computed tomography scan every 4 cycles results best tumor responses using response evaluation criteria solid tumor criteria complete response 1 patient partial response 4 patients stable disease 6 patients 6 mo follow response rate 38 4 95 ci 12 5 89 disease control rate 84 5 95 ci 42 100 seven deaths occurred time analysis progression free survival 8 mo 95 ci 7 16 median overall survival 20 mo 95 ci 8 48 grade 4 toxic events observed four grade 3 hematological toxicities one grade 3 digestive toxicity occurred adaptive reduction chemotherapy dosage required 2 patients due hematological toxicity delay chemotherapy cycles required 3 patients conclusion folfiri plus bevacizumab combination treatment showed promising efficacy safety second line treatment metastatic intrahepatic cholangiocarcinoma failure first line treatment gemcitabine plus oxaliplatin chemotherapy pubmed","probabilities":0.9799733,"Title":"FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma","Abstract":"AIM: To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic cholangiocarcinoma. METHODS: Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory to first-line therapy consisting of gemcitabine plus oxaliplatin-based first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI [irinotecan (180 mg/m² i.v. over 90 min) concurrently with folinic acid (400 mg/m² i.v. over 120 min) followed by fluorouracil (400 mg/m² i.v. bolus) then fluorouracil 2400 mg/m² intravenous infusion over 46 h] and bevacizumab (5 mg/kg) every 2 wk. Tumor response was evaluated by computed tomography scan every 4 cycles. RESULTS: The best tumor responses using response evaluation criteria in solid tumor criteria were: complete response for 1 patient, partial response for 4 patients, and stable disease for 6 patients after 6 mo of follow-up. The response rate was 38.4% (95%CI: 12.5-89) and the disease control rate was 84.5% (95%CI: 42-100). Seven deaths occurred at the time of analysis, progression free survival was 8 mo (95%CI: 7-16), and median overall survival was 20 mo (95%CI: 8-48). No grade 4 toxic events were observed. Four grade 3 hematological toxicities and one grade 3 digestive toxicity occurred. An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity, and a delay in chemotherapy cycles was required for 3 patients. CONCLUSION: FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"FOLFIRI plus bevacizumab as a second-line therapy for metastatic intrahepatic cholangiocarcinoma AIM: To evaluate the efficacy and tolerance of FOLFIRI plus bevacizumab treatment outcome as second-line treatment for metastatic intrahepatic cholangiocarcinoma. METHODS: Thirteen consecutive patients with metastatic intrahepatic cholangiocarcinoma who were refractory to first-line therapy consisting of gemcitabine plus oxaliplatin-based first-line chemotherapy given intravenously via intra-arterial infusion were treated with FOLFIRI [irinotecan (180 mg/m² i.v. over 90 min) concurrently with folinic acid (400 mg/m² i.v. over 120 min) followed by fluorouracil (400 mg/m² i.v. bolus) then fluorouracil 2400 mg/m² intravenous infusion over 46 h] and bevacizumab (5 mg/kg) every 2 wk. Tumor response was evaluated by computed tomography scan every 4 cycles. RESULTS: The best tumor responses using response evaluation criteria in solid tumor criteria were: complete response for 1 patient, partial response for 4 patients, and stable disease for 6 patients after 6 mo of follow-up. The response rate was 38.4% (95%CI: 12.5-89) and the disease control rate was 84.5% (95%CI: 42-100). Seven deaths occurred at the time of analysis, progression free survival was 8 mo (95%CI: 7-16), and median overall survival was 20 mo (95%CI: 8-48). No grade 4 toxic events were observed. Four grade 3 hematological toxicities and one grade 3 digestive toxicity occurred. An adaptive reduction in chemotherapy dosage was required in 2 patients due to hematological toxicity, and a delay in chemotherapy cycles was required for 3 patients. CONCLUSION: FOLFIRI plus bevacizumab combination treatment showed promising efficacy and safety as second-line treatment for metastatic intrahepatic cholangiocarcinoma after failure of the first-line treatment of gemcitabine plus oxaliplatin chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"minimally invasive open gallbladder cancer resections 30 vs 90 day mortality background minimally invasive surgery increasingly used gallbladder cancer resection postoperative mortality 30 days low 90 day mortality underreported methods using national cancer database 1998 2012 resection patients included thirty 90 day mortality rates compared results total 36 067 patients identified 19 139 53 underwent resection median age 71 years 70 7 female ninety day mortality following surgical resection 2 3 fold higher 30 mortality 17 1 vs 7 4 statistically significant increase 30 90 day mortality poorly differentiated tumors presence lymphovascular invasion tumor stage incomplete surgical resection low volume centers p 0 001 even 1885 patients underwent minimally invasive resection 2010 2012 90 day mortality 2 8 fold higher 30 day mortality 12 0 vs 4 3 conclusions ninety day mortality following gallbladder cancer resection significantly higher 30 day mortality postoperative mortality associated tumor grade lymphovascular invasion tumor stage type completeness surgical resection well type volume facility pubmed","probabilities":0.9799733,"Title":"Minimally invasive and open gallbladder cancer resections: 30- vs 90-day mortality","Abstract":"BACKGROUND: Minimally invasive surgery is increasingly used for gallbladder cancer resection. Postoperative mortality at 30 days is low, but 90-day mortality is underreported. METHODS: Using National Cancer Database (1998-2012), all resection patients were included. Thirty- and 90-day mortality rates were compared. RESULTS: A total of 36 067 patients were identified, 19 139 (53%) of whom underwent resection. Median age was 71 years and 70.7% were female. Ninety-day mortality following surgical resection was 2.3-fold higher than 30-mortality (17.1% vs 7.4%). There was a statistically significant increase in 30- and 90-day mortality with poorly differentiated tumors, presence of lymphovascular invasion, tumor stage, incomplete surgical resection and low-volume centers (P<0.001 for all). Even for the 1885 patients who underwent minimally invasive resection between 2010 and 2012, the 90-day mortality was 2.8-fold higher than the 30-day mortality (12.0% vs 4.3%). CONCLUSIONS: Ninety-day mortality following gallbladder cancer resection is significantly higher than 30-day mortality. Postoperative mortality is associated with tumor grade, lymphovascular invasion, tumor stage, type and completeness of surgical resection as well as type and volume of facility.","Source":"PubMed","category":"HUMAN","training_data":"Minimally invasive and open gallbladder cancer resections: 30- vs 90-day mortality BACKGROUND: Minimally invasive surgery is increasingly used for gallbladder cancer resection. Postoperative mortality at 30 days is low, but 90-day mortality is underreported. METHODS: Using National Cancer Database (1998-2012), all resection patients were included. Thirty- and 90-day mortality rates were compared. RESULTS: A total of 36 067 patients were identified, 19 139 (53%) of whom underwent resection. Median age was 71 years and 70.7% were female. Ninety-day mortality following surgical resection was 2.3-fold higher than 30-mortality (17.1% vs 7.4%). There was a statistically significant increase in 30- and 90-day mortality with poorly differentiated tumors, presence of lymphovascular invasion, tumor stage, incomplete surgical resection and low-volume centers (P<0.001 for all). Even for the 1885 patients who underwent minimally invasive resection between 2010 and 2012, the 90-day mortality was 2.8-fold higher than the 30-day mortality (12.0% vs 4.3%). CONCLUSIONS: Ninety-day mortality following gallbladder cancer resection is significantly higher than 30-day mortality. Postoperative mortality is associated with tumor grade, lymphovascular invasion, tumor stage, type and completeness of surgical resection as well as type and volume of facility. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma new insights disease pathogenesis biology cholangiocarcinomas rare malignant tumors whose incidence increasing worldwide risk factors malignancy include infectious non infectious diseases characterized chronic inflammation bile duct epithelia diagnosis cancers remains difficult lack sensitive diagnostic tests prognosis poor probably lack effective treatments unresectable cancer pubmed","probabilities":0.9799733,"Title":"Cholangiocarcinoma: new insights into disease pathogenesis and biology","Abstract":"Cholangiocarcinomas are rare malignant tumors whose incidence is increasing worldwide. Risk factors for this malignancy include both infectious and non-infectious diseases characterized by chronic inflammation of the bile duct epithelia. Diagnosis of these cancers remains difficult because of the lack of sensitive diagnostic tests. The prognosis is poor probably because of the lack of effective treatments for unresectable cancer.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma: new insights into disease pathogenesis and biology Cholangiocarcinomas are rare malignant tumors whose incidence is increasing worldwide. Risk factors for this malignancy include both infectious and non-infectious diseases characterized by chronic inflammation of the bile duct epithelia. Diagnosis of these cancers remains difficult because of the lack of sensitive diagnostic tests. The prognosis is poor probably because of the lack of effective treatments for unresectable cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"decreased expression chromodomain helicase dna binding protein 5 unfavorable prognostic marker patients primary gallbladder carcinoma aim chromodomain helicase dna binding protein 5 chd5 plays role normal neural development tumorigenesis various human cancers however role primary gallbladder carcinoma pgc still unclear aim study investigate chd5 expression pgc clinical significance methods chd5 mrna protein expression 120 pgc 20 normal gallbladder specimens determined quantitative reverse transcription polymerase chain reaction qrt pcr western blotting analysis respectively results expression levels chd5 mrna protein pgc tissues significantly lower normal epithelium gallbladder mrna p 0 006 protein p 0 01 chd5 mrna expression closely correlated protein expression r 0 8 p 0 001 additionally low expression chd5 protein significantly associated high pathologic stage p 0 01 clinical stage p 0 008 advanced histologic grade p 0 009 expression levels chd5 protein pgc tissues positive nodal metastasis also significantly lower without p 0 01 survival analysis showed low chd5 expression associated shorter disease free p 0 01 overall survival p 0 008 compared high chd5 expression pgc patients furthermore multivariate analyses showed decreased expression chd5 independent prognostic marker unfavorable disease free p 0 01 overall survival p 0 006 conclusion chd5 may involved carcinogenesis pgc regulation may significantly correlated unfavorable clinicopathologic features including poor overall disease free survival patients pubmed","probabilities":0.75,"Title":"Decreased expression of chromodomain helicase DNA-binding protein 5 is an unfavorable prognostic marker in patients with primary gallbladder carcinoma","Abstract":"AIM: Chromodomain helicase DNA-binding protein 5 (CHD5) plays a role in normal neural development and in tumorigenesis of various human cancers. However, its role in primary gallbladder carcinoma (PGC) is still unclear. The aim of this study was to investigate CHD5 expression in PGC and its clinical significance. METHODS: CHD5 mRNA and protein expression in 120 PGC and 20 normal gallbladder specimens was determined by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) and Western blotting analysis, respectively. RESULTS: The expression levels of CHD5 mRNA and protein in PGC tissues were both significantly lower than those in the normal epithelium of the gallbladder (mRNA: P = 0.006; protein: P = 0.01). CHD5 mRNA expression was closely correlated with its protein expression (r = 0.8; P < 0.001). Additionally, the low expression of CHD5 protein was significantly associated with high pathologic T stage (P = 0.01) and clinical stage (P = 0.008), and advanced histologic grade (P = 0.009). The expression levels of CHD5 protein in PGC tissues with positive nodal metastasis were also significantly lower than those without (P = 0.01). Survival analysis showed that low CHD5 expression was associated with shorter disease-free (P = 0.01) and overall survival (P = 0.008) compared to those with high CHD5 expression in PGC patients. Furthermore, multivariate analyses showed that the decreased expression of CHD5 was an independent prognostic marker for both unfavorable disease-free (P = 0.01) and overall survival (P = 0.006). CONCLUSION: CHD5 may be involved in carcinogenesis of PGC and its down-regulation may be significantly correlated with unfavorable clinicopathologic features including poor overall and disease-free survival in patients.","Source":"PubMed","category":"ANIMAL","training_data":"Decreased expression of chromodomain helicase DNA-binding protein 5 is an unfavorable prognostic marker in patients with primary gallbladder carcinoma AIM: Chromodomain helicase DNA-binding protein 5 (CHD5) plays a role in normal neural development and in tumorigenesis of various human cancers. However, its role in primary gallbladder carcinoma (PGC) is still unclear. The aim of this study was to investigate CHD5 expression in PGC and its clinical significance. METHODS: CHD5 mRNA and protein expression in 120 PGC and 20 normal gallbladder specimens was determined by quantitative reverse transcription-polymerase chain reaction (QRT-PCR) and Western blotting analysis, respectively. RESULTS: The expression levels of CHD5 mRNA and protein in PGC tissues were both significantly lower than those in the normal epithelium of the gallbladder (mRNA: P = 0.006; protein: P = 0.01). CHD5 mRNA expression was closely correlated with its protein expression (r = 0.8; P < 0.001). Additionally, the low expression of CHD5 protein was significantly associated with high pathologic T stage (P = 0.01) and clinical stage (P = 0.008), and advanced histologic grade (P = 0.009). The expression levels of CHD5 protein in PGC tissues with positive nodal metastasis were also significantly lower than those without (P = 0.01). Survival analysis showed that low CHD5 expression was associated with shorter disease-free (P = 0.01) and overall survival (P = 0.008) compared to those with high CHD5 expression in PGC patients. Furthermore, multivariate analyses showed that the decreased expression of CHD5 was an independent prognostic marker for both unfavorable disease-free (P = 0.01) and overall survival (P = 0.006). CONCLUSION: CHD5 may be involved in carcinogenesis of PGC and its down-regulation may be significantly correlated with unfavorable clinicopathologic features including poor overall and disease-free survival in patients. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"gallbladder cancer netherlands incidence treatment survival patterns since 1989 background examine recent trends gallbladder cancer gbc general population western world cancer registration data gbc netherlands analyzed methods trends incidence treatment survival according gender age stage disease 1989 2008 3 917 patients studied rates age standardized european standard population european standardized rates esr results incidence rate gbc netherlands decreased rapidly period 1989 2008 except males younger 60 years overall survival remained stable short term 3 month long term 5 year relative survival among surgically treated patients increased significantly treatment patterns gbc changed surgery decreased 55 1989 38 2008 p 0 001 chemotherapy irradiation increased 1 0 5 8 p 0 001 receiving best supportive care increased 44 1989 57 2008 p 0 001 conclusion incidence rate gbc netherlands decreased rapidly treatment patterns gbc changed survival among surgically treated patients increased pubmed","probabilities":0.9799733,"Title":"Gallbladder cancer in the Netherlands: incidence, treatment and survival patterns since 1989","Abstract":"BACKGROUND: To examine recent trends in gallbladder cancer (GBC) in the general population in the Western world, cancer registration data on GBC in the Netherlands were analyzed. METHODS: Trends in incidence, treatment and survival, according to gender, age and stage of disease, between 1989 and 2008 for 3,917 patients were studied. Rates were age-standardized to the European standard population (European Standardized Rates - ESR). RESULTS: The incidence rate for GBC in the Netherlands decreased rapidly during the period of 1989-2008, except for males younger than 60 years. Overall survival remained stable, short-term (3-month) and long-term (5-year) relative survival among surgically treated patients increased significantly. Treatment patterns for GBC changed. Surgery decreased from 55% in 1989 to 38% in 2008 (p < 0.001). Chemotherapy and/or irradiation increased from 1.0 to 5.8% (p < 0.001). Receiving best supportive care increased from 44% in 1989 to 57% in 2008 (p < 0.001). CONCLUSION: The incidence rate for GBC in the Netherlands has decreased rapidly. Treatment patterns for GBC have changed and survival among surgically treated patients has increased.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder cancer in the Netherlands: incidence, treatment and survival patterns since 1989 BACKGROUND: To examine recent trends in gallbladder cancer (GBC) in the general population in the Western world, cancer registration data on GBC in the Netherlands were analyzed. METHODS: Trends in incidence, treatment and survival, according to gender, age and stage of disease, between 1989 and 2008 for 3,917 patients were studied. Rates were age-standardized to the European standard population (European Standardized Rates - ESR). RESULTS: The incidence rate for GBC in the Netherlands decreased rapidly during the period of 1989-2008, except for males younger than 60 years. Overall survival remained stable, short-term (3-month) and long-term (5-year) relative survival among surgically treated patients increased significantly. Treatment patterns for GBC changed. Surgery decreased from 55% in 1989 to 38% in 2008 (p < 0.001). Chemotherapy and/or irradiation increased from 1.0 to 5.8% (p < 0.001). Receiving best supportive care increased from 44% in 1989 to 57% in 2008 (p < 0.001). CONCLUSION: The incidence rate for GBC in the Netherlands has decreased rapidly. Treatment patterns for GBC have changed and survival among surgically treated patients has increased. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact morphological status long term outcome among patients undergoing liver surgery intrahepatic cholangiocarcinoma background influence morphological status long term outcome patients undergoing liver resection intrahepatic cholangiocarcinoma icc poorly defined sought study impact morphological status overall survival os patients undergoing curative intent resection icc methods total 1083 patients underwent liver resection icc 1990 2015 identified data clinicopathological characteristics operative details morphological status recorded analyzed propensity score matched analysis performed reduce confounding biases results among 1083 patients 941 86 9 mass forming mf intraductal growth ig type 142 13 1 periductal infiltrating pi mf pi components mf pi icc patients mf ig icc 5 year os 41 8 95 confidence interval ci 37 7 45 9 compared 25 5 95 ci 17 3 34 4 patients pi mf pi p 0 001 morphological type found independent predictor os patients pi mf pi icc higher hazard death hazard ratio hr 1 42 95 ci 1 11 1 82 p 0 006 compared patients mf ig icc compared t1a t1b t2 mf ig tumors t1a t1b t2 pi mf pi t3 t4 pi mf pi tumors associated increased risk death hr 1 47 vs 3 59 conversely patients t3 t4 mf ig tumors similar risk death compared t1a t1b t2 mf ig patients p 0 95 conclusion among patients undergoing curative intent resection icc morphological status predictor long term outcome patients pi mf pi icc approximately 45 increased risk death long term compared patients mf ig icc pubmed","probabilities":0.9799733,"Title":"Impact of Morphological Status on Long-Term Outcome Among Patients Undergoing Liver Surgery for Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: The influence of morphological status on the long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) is poorly defined. We sought to study the impact of morphological status on overall survival (OS) of patients undergoing curative-intent resection for ICC. METHODS: A total of 1083 patients who underwent liver resection for ICC between 1990 and 2015 were identified. Data on clinicopathological characteristics, operative details, and morphological status were recorded and analyzed. A propensity score-matched analysis was performed to reduce confounding biases. RESULTS: Among 1083 patients, 941(86.9%) had a mass-forming (MF) or intraductal-growth (IG) type, while 142 (13.1%) had a periductal-infiltrating (PI) or MF with PI components (MF + PI) ICC. Patients with an MF/IG ICC had a 5-year OS of 41.8% (95% confidence interval [CI] 37.7-45.9) compared with 25.5% (95% CI 17.3-34.4) for patients with a PI/MF + PI (p < 0.001). Morphological type was found to be an independent predictor of OS as patients with a PI/MF + PI ICC had a higher hazard of death (hazard ratio [HR] 1.42, 95% CI 1.11-1.82; p = 0.006) compared with patients who had an MF/IG ICC. Compared with T1a-T1b-T2 MF/IG tumors, T1a-T1b-T2 PI/MF + PI and T3-T4 PI/MF + PI tumors were associated with an increased risk of death (HR 1.47 vs. 3.59). Conversely, patients with T3-T4 MF/IG tumors had a similar risk of death compared with T1a-T1b-T2 MF/IG patients (p = 0.95). CONCLUSION: Among patients undergoing curative-intent resection of ICC, morphological status was a predictor of long-term outcome. Patients with PI or MF + PI ICC had an approximately 45% increased risk of death long-term compared with patients who had an MF or IG ICC.","Source":"PubMed","category":"HUMAN","training_data":"Impact of Morphological Status on Long-Term Outcome Among Patients Undergoing Liver Surgery for Intrahepatic Cholangiocarcinoma BACKGROUND: The influence of morphological status on the long-term outcome of patients undergoing liver resection for intrahepatic cholangiocarcinoma (ICC) is poorly defined. We sought to study the impact of morphological status on overall survival (OS) of patients undergoing curative-intent resection for ICC. METHODS: A total of 1083 patients who underwent liver resection for ICC between 1990 and 2015 were identified. Data on clinicopathological characteristics, operative details, and morphological status were recorded and analyzed. A propensity score-matched analysis was performed to reduce confounding biases. RESULTS: Among 1083 patients, 941(86.9%) had a mass-forming (MF) or intraductal-growth (IG) type, while 142 (13.1%) had a periductal-infiltrating (PI) or MF with PI components (MF + PI) ICC. Patients with an MF/IG ICC had a 5-year OS of 41.8% (95% confidence interval [CI] 37.7-45.9) compared with 25.5% (95% CI 17.3-34.4) for patients with a PI/MF + PI (p < 0.001). Morphological type was found to be an independent predictor of OS as patients with a PI/MF + PI ICC had a higher hazard of death (hazard ratio [HR] 1.42, 95% CI 1.11-1.82; p = 0.006) compared with patients who had an MF/IG ICC. Compared with T1a-T1b-T2 MF/IG tumors, T1a-T1b-T2 PI/MF + PI and T3-T4 PI/MF + PI tumors were associated with an increased risk of death (HR 1.47 vs. 3.59). Conversely, patients with T3-T4 MF/IG tumors had a similar risk of death compared with T1a-T1b-T2 MF/IG patients (p = 0.95). CONCLUSION: Among patients undergoing curative-intent resection of ICC, morphological status was a predictor of long-term outcome. Patients with PI or MF + PI ICC had an approximately 45% increased risk of death long-term compared with patients who had an MF or IG ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance neutrophil lymphocyte ratio biliary tract cancers systematic review meta analysis background inflammation considered perform crucial roles development metastasis malignancies heightened neutrophil lymphocyte ratio described associated detrimental survivals different malignancies debate remains impact heightened neutrophil lymphocyte ratio survivals biliary tract cancer review evaluated prognostic value neutrophil lymphocyte ratio biliary tract cancer methods medline cochrane library embase chinese sinomed systematically searched relevant articles associations neutrophil lymphocyte ratio long term outcomes expressed hazard ratios 95 confidence intervals odds ratio utilized assess association neutrophil lymphocyte ratio clinicopathological parameters results fourteen studies consisting 3217 patients analyzed 1278 39 73 high pretreatment neutrophil lymphocyte ratio group 1939 60 27 low pretreatment neutrophil lymphocyte ratio one results proved heightened pretreatment neutrophil lymphocyte ratio significantly associated detrimental overall survival relapse free survival biliary tract cancer patients addition elevated neutrophil lymphocyte ratio positively correlated higher carbohydrate antigen 19 9 levels advanced tnm staging greater lymph node involvement conclusion meta analysis marked increased pretreatment neutrophil lymphocyte ratio significantly linked detrimental long term outcomes clinicopathological parameters patients biliary tract cancer pubmed","probabilities":0.9799733,"Title":"Prognostic significance of neutrophil-to-lymphocyte ratio in biliary tract cancers: a systematic review and meta-analysis","Abstract":"BACKGROUND: Inflammation was considered to perform crucial roles in the development and metastasis of malignancies. A heightened neutrophil-lymphocyte ratio has been described to be associated with detrimental survivals in different malignancies. Debate remains over the impact of heightened neutrophil-lymphocyte ratio on survivals in biliary tract cancer. The review evaluated the prognostic value of neutrophil-lymphocyte ratio in biliary tract cancer. METHODS: MEDLINE, the Cochrane Library, EMBASE, and the Chinese SinoMed were systematically searched for relevant articles. Associations between neutrophil-lymphocyte ratio and long-term outcomes were expressed as the hazard ratios and 95% confidence intervals. The odds ratio was utilized to assess the association between neutrophil-lymphocyte ratio and clinicopathological parameters. RESULTS: Fourteen studies consisting of 3217 patients were analyzed: 1278 (39.73%) in the high pretreatment neutrophil-lymphocyte ratio group and 1939 (60.27%) in the low pretreatment neutrophil-lymphocyte ratio one. The results proved that heightened pretreatment neutrophil-lymphocyte ratio was significantly associated with detrimental overall survival and relapse free survival for biliary tract cancer patients. In addition, elevated neutrophil-lymphocyte ratio was positively correlated with higher carbohydrate antigen 19-9 levels, advanced TNM staging and greater lymph node involvement. CONCLUSION: This meta-analysis marked that an increased pretreatment neutrophil-lymphocyte ratio was significantly linked with detrimental long-term outcomes and clinicopathological parameters for patients with biliary tract cancer.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of neutrophil-to-lymphocyte ratio in biliary tract cancers: a systematic review and meta-analysis BACKGROUND: Inflammation was considered to perform crucial roles in the development and metastasis of malignancies. A heightened neutrophil-lymphocyte ratio has been described to be associated with detrimental survivals in different malignancies. Debate remains over the impact of heightened neutrophil-lymphocyte ratio on survivals in biliary tract cancer. The review evaluated the prognostic value of neutrophil-lymphocyte ratio in biliary tract cancer. METHODS: MEDLINE, the Cochrane Library, EMBASE, and the Chinese SinoMed were systematically searched for relevant articles. Associations between neutrophil-lymphocyte ratio and long-term outcomes were expressed as the hazard ratios and 95% confidence intervals. The odds ratio was utilized to assess the association between neutrophil-lymphocyte ratio and clinicopathological parameters. RESULTS: Fourteen studies consisting of 3217 patients were analyzed: 1278 (39.73%) in the high pretreatment neutrophil-lymphocyte ratio group and 1939 (60.27%) in the low pretreatment neutrophil-lymphocyte ratio one. The results proved that heightened pretreatment neutrophil-lymphocyte ratio was significantly associated with detrimental overall survival and relapse free survival for biliary tract cancer patients. In addition, elevated neutrophil-lymphocyte ratio was positively correlated with higher carbohydrate antigen 19-9 levels, advanced TNM staging and greater lymph node involvement. CONCLUSION: This meta-analysis marked that an increased pretreatment neutrophil-lymphocyte ratio was significantly linked with detrimental long-term outcomes and clinicopathological parameters for patients with biliary tract cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"dysregulation mir 148a glut1 axis promotes progression chemoresistance human intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icca highly fatal malignant cancer worldwide elucidating underlying molecular mechanism icca progression critical identification new therapeutic targets present study explored role mir 148a glut1 axis progression icca expression glut1 detected using immunohistochemistry western blot assays real time polymerase chain reaction effects glut1 cell proliferation invasion chemoresistance investigated vitro vivo luciferase reporter assay used explore effect mir 148a glut1 expression glut1 overexpressed icca tissues glut1 overexpression associated shorter overall disease free survival knockdown glut1 reduced overexpression glut1 promoted proliferation motility invasiveness icca cells vitro vivo silencing glut1 significantly sensitized icca cells gemcitabine vitro vivo glut1 directly regulated mir 148a whose downregulation associated proliferation migration invasion icca cells wzb117 glut1 inhibitor inhibited tumor growth icca patient derived xenograft model results indicate downregulation mir 148a levels results glut1 overexpression icca leading icca progression gemcitabine resistance stn","probabilities":0.9467213,"Title":"Dysregulation Of The Mir-148A-Glut1 Axis Promotes The Progression And Chemoresistance Of Human Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (iCCA) is a highly fatal malignant cancer worldwide. Elucidating the underlying molecular mechanism of iCCA progression is critical for the identification of new therapeutic targets. The present study explored the role of the miR-148a-GLUT1 axis in the progression of iCCA. The expression of GLUT1 was detected by using immunohistochemistry, western blot assays, and real-time polymerase chain reaction. The effects of GLUT1 on cell proliferation, invasion, and chemoresistance were investigated both in vitro and in vivo. A luciferase reporter assay was used to explore the effect of miR-148a on GLUT1 expression. GLUT1 was overexpressed in iCCA tissues. GLUT1 overexpression was associated with shorter overall and disease-free survival. Knockdown of GLUT1 reduced, while overexpression of GLUT1 promoted, the proliferation, motility, and invasiveness of iCCA cells in vitro and in vivo. Silencing GLUT1 significantly sensitized iCCA cells to gemcitabine in vitro and in vivo. GLUT1 was directly regulated by miR-148a, whose downregulation was associated with the proliferation, migration, and invasion of iCCA cells. WZB117, a GLUT1 inhibitor, inhibited tumor growth in an iCCA patient-derived xenograft model. These results indicate that downregulation of miR-148a levels results in GLUT1 overexpression in iCCA, leading to iCCA progression and gemcitabine resistance.","Source":"STN","category":"ANIMAL","training_data":"Dysregulation Of The Mir-148A-Glut1 Axis Promotes The Progression And Chemoresistance Of Human Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma (iCCA) is a highly fatal malignant cancer worldwide. Elucidating the underlying molecular mechanism of iCCA progression is critical for the identification of new therapeutic targets. The present study explored the role of the miR-148a-GLUT1 axis in the progression of iCCA. The expression of GLUT1 was detected by using immunohistochemistry, western blot assays, and real-time polymerase chain reaction. The effects of GLUT1 on cell proliferation, invasion, and chemoresistance were investigated both in vitro and in vivo. A luciferase reporter assay was used to explore the effect of miR-148a on GLUT1 expression. GLUT1 was overexpressed in iCCA tissues. GLUT1 overexpression was associated with shorter overall and disease-free survival. Knockdown of GLUT1 reduced, while overexpression of GLUT1 promoted, the proliferation, motility, and invasiveness of iCCA cells in vitro and in vivo. Silencing GLUT1 significantly sensitized iCCA cells to gemcitabine in vitro and in vivo. GLUT1 was directly regulated by miR-148a, whose downregulation was associated with the proliferation, migration, and invasion of iCCA cells. WZB117, a GLUT1 inhibitor, inhibited tumor growth in an iCCA patient-derived xenograft model. These results indicate that downregulation of miR-148a levels results in GLUT1 overexpression in iCCA, leading to iCCA progression and gemcitabine resistance. STN","prediction_labels":"ANIMAL"},{"cleaned":"immunohistochemical expression vascular endothelial growth factor advanced gallbladder carcinoma gallbladder cancer gbc highly fatal disease poor prognosis therapeutic alternatives molecular mechanisms involved pathogenesis gbc remain poorly understood vascular endothelial growth factor vegf potent proangiogenic agent involved carcinogenesis many human tumors attractive target cancer therapy characterized vegf expression advanced gbc relation clinicopathologic features vegf expression examined immunohistochemistry tissue microarrays containing 224 advanced gallbladder carcinomas 39 chronic cholecystitis cases classified low high expression evaluate association vegf expression level clinicopathologic variables kaplan meier method used estimate survival function time survival differences analyzed log rank test high expression vegf observed 81 183 224 tumors 5 1 2 39 chronic cholecystitis p 0 0001 vegf expression significant relationship histologic grade tnm stage p 0 05 moreover 5 year survival analysis indicated high expression vegf associated poor prognosis patients advanced gbc p 0 0116 results indicate vegf highly expressed gbc correlates poor prognosis suggesting vegf expression used biomarker predicting malignant behavior identifying subset patients may benefit anti vegf therapies stn","probabilities":0.8333333,"Title":"Immunohistochemical Expression Of Vascular Endothelial Growth Factor A In Advanced Gallbladder Carcinoma","Abstract":"Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The molecular mechanisms involved in the pathogenesis of GBC remain poorly understood. The vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic agent involved in the carcinogenesis of many human tumors and is an attractive target for cancer therapy. We characterized VEGF-A expression in advanced GBC and its relation to clinicopathologic features. VEGF-A expression was examined by immunohistochemistry in tissue microarrays containing 224 advanced gallbladder carcinomas and 39 chronic cholecystitis. The cases were classified as low or high expression to evaluate the association of VEGF-A expression level with clinicopathologic variables. The Kaplan-Meier method was used to estimate survival as a function of time, and survival differences were analyzed by the log-rank test. High expression of VEGF-A was observed in 81% (183/224) of tumors and 5.1% (2/39) of chronic cholecystitis (P<0.0001). The VEGF-A expression had a significant relationship with histologic grade and TNM stage (P<0.05). Moreover, 5-year survival analysis indicated that high expression of VEGF-A is associated with a poor prognosis in patients with advanced GBC (P=0.0116). Our results indicate that VEGF-A is highly expressed in GBC and correlates with poor prognosis, suggesting that VEGF-A expression could be used as a biomarker for predicting malignant behavior and for identifying a subset of patients who may benefit from anti-VEGF-A therapies.","Source":"STN","category":"ANIMAL","training_data":"Immunohistochemical Expression Of Vascular Endothelial Growth Factor A In Advanced Gallbladder Carcinoma Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The molecular mechanisms involved in the pathogenesis of GBC remain poorly understood. The vascular endothelial growth factor A (VEGF-A) is a potent proangiogenic agent involved in the carcinogenesis of many human tumors and is an attractive target for cancer therapy. We characterized VEGF-A expression in advanced GBC and its relation to clinicopathologic features. VEGF-A expression was examined by immunohistochemistry in tissue microarrays containing 224 advanced gallbladder carcinomas and 39 chronic cholecystitis. The cases were classified as low or high expression to evaluate the association of VEGF-A expression level with clinicopathologic variables. The Kaplan-Meier method was used to estimate survival as a function of time, and survival differences were analyzed by the log-rank test. High expression of VEGF-A was observed in 81% (183/224) of tumors and 5.1% (2/39) of chronic cholecystitis (P<0.0001). The VEGF-A expression had a significant relationship with histologic grade and TNM stage (P<0.05). Moreover, 5-year survival analysis indicated that high expression of VEGF-A is associated with a poor prognosis in patients with advanced GBC (P=0.0116). Our results indicate that VEGF-A is highly expressed in GBC and correlates with poor prognosis, suggesting that VEGF-A expression could be used as a biomarker for predicting malignant behavior and for identifying a subset of patients who may benefit from anti-VEGF-A therapies. STN","prediction_labels":"HUMAN"},{"cleaned":"excision repair cross complementing gene 1 ribonucleotide reductase subunit m1 ribonucleotide reductase subunit m2 human equilibrative nucleoside transporter 1 expression prognostic value biliary tract malignancy background tumor expression excision cross complementing gene 1 ercc1 human equilibrative nucleoside transporter 1 hent1 ribonucleotide reductase subunit m1 rrm1 ribonucleotide reductase subunit m2 rrm2 associated efficacy platinum gemcitabine chemotherapy authors report recently demonstrated high ercc1 rrm2 expression levels independent negative prognostic markers survival early stage pancreas cancer differential expression prognostic value biomarkers biliary tract malignancy btm unknown methods total 63 patients tissue available analysis selected prospective database patients n 104 underwent resection btm intrahepatic hilar distal cholangiocarcinoma gallbladder carcinoma january 2000 december 2008 immunohistochemistry ercc1 hent1 rrm1 rrm2 expression performed staining scored single pathologist blinded patient outcomes results median patient age 67 years median overall survival os 16 2 months median follow 32 7 months 3 btms 4 8 high ercc1 expression 92 1 81 btms exhibited high hent1 rrm1 expression respectively rrm2 expression varied 32 tumors demonstrated high rrm2 expression ercc1 rrm1 associated os high rrm2 expression associated trend toward improved os 30 8 months vs 16 2 months p 06 high hent1 expression associated improved os 17 7 months vs 9 5 months p 04 conclusions btms exhibited low ercc1 expression high hent1 rrm1 expression whereas rrm2 expression levels varied high expression hent1 associated improved os findings may implications selection chemotherapy agents gemcitabine vs platinum stratification patients chemotherapy trials assess outcome pubmed","probabilities":0.8684211,"Title":"Excision repair cross-complementing gene-1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and human equilibrative nucleoside transporter-1 expression and prognostic value in biliary tract malignancy","Abstract":"BACKGROUND: Tumor expression of excision cross-complementing gene-1 (ERCC1), human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunit M1 (RRM1), and ribonucleotide reductase subunit M2 (RRM2), is associated with the efficacy of platinum and gemcitabine chemotherapy. The authors of this report recently demonstrated that high ERCC1 and RRM2 expression levels are independent negative prognostic markers for survival in early stage pancreas cancer. The differential expression and prognostic value of these biomarkers in biliary tract malignancy (BTM) is unknown. METHODS: In total, 63 patients who had tissue available for analysis were selected from a prospective database of all patients (n = 104) who underwent resection of BTM (intrahepatic, hilar, or distal cholangiocarcinoma; gallbladder carcinoma) between January 2000 and December 2008. Immunohistochemistry for ERCC1, hENT1, RRM1, and RRM2 expression was performed. Staining was scored by a single pathologist who was blinded to patient outcomes. RESULTS: The median patient age was 67 years. The median overall survival (OS) was 16.2 months, and the median follow-up was 32.7 months. Only 3 BTMs (4.8%) had high ERCC1 expression, and 92.1% and 81% of BTMs exhibited high hENT1 and RRM1 expression, respectively. RRM2 expression varied, and 32% of tumors demonstrated high RRM2 expression. ERCC1 and RRM1 were not associated with OS. High RRM2 expression was associated with a trend toward improved OS (30.8 months vs 16.2 months; P = .06), and high hENT1 expression was associated with improved OS (17.7 months vs 9.5 months; P = .04). CONCLUSIONS: Most BTMs exhibited low ERCC1 expression and high hENT1 and RRM1 expression, whereas RRM2 expression levels varied. High expression of hENT1 was associated with improved OS. These findings may have implications for the selection of chemotherapy agents (gemcitabine vs platinum) and the stratification of patients in chemotherapy trials that assess outcome.","Source":"PubMed","category":"HUMAN","training_data":"Excision repair cross-complementing gene-1, ribonucleotide reductase subunit M1, ribonucleotide reductase subunit M2, and human equilibrative nucleoside transporter-1 expression and prognostic value in biliary tract malignancy BACKGROUND: Tumor expression of excision cross-complementing gene-1 (ERCC1), human equilibrative nucleoside transporter 1 (hENT1), ribonucleotide reductase subunit M1 (RRM1), and ribonucleotide reductase subunit M2 (RRM2), is associated with the efficacy of platinum and gemcitabine chemotherapy. The authors of this report recently demonstrated that high ERCC1 and RRM2 expression levels are independent negative prognostic markers for survival in early stage pancreas cancer. The differential expression and prognostic value of these biomarkers in biliary tract malignancy (BTM) is unknown. METHODS: In total, 63 patients who had tissue available for analysis were selected from a prospective database of all patients (n = 104) who underwent resection of BTM (intrahepatic, hilar, or distal cholangiocarcinoma; gallbladder carcinoma) between January 2000 and December 2008. Immunohistochemistry for ERCC1, hENT1, RRM1, and RRM2 expression was performed. Staining was scored by a single pathologist who was blinded to patient outcomes. RESULTS: The median patient age was 67 years. The median overall survival (OS) was 16.2 months, and the median follow-up was 32.7 months. Only 3 BTMs (4.8%) had high ERCC1 expression, and 92.1% and 81% of BTMs exhibited high hENT1 and RRM1 expression, respectively. RRM2 expression varied, and 32% of tumors demonstrated high RRM2 expression. ERCC1 and RRM1 were not associated with OS. High RRM2 expression was associated with a trend toward improved OS (30.8 months vs 16.2 months; P = .06), and high hENT1 expression was associated with improved OS (17.7 months vs 9.5 months; P = .04). CONCLUSIONS: Most BTMs exhibited low ERCC1 expression and high hENT1 and RRM1 expression, whereas RRM2 expression levels varied. High expression of hENT1 was associated with improved OS. These findings may have implications for the selection of chemotherapy agents (gemcitabine vs platinum) and the stratification of patients in chemotherapy trials that assess outcome. PubMed","prediction_labels":"HUMAN"},{"cleaned":"number parity risk gallbladder cancer systematic review dose response meta analysis observational studies background current epidemiological evidence suggests association parity risk gallbladder cancer gbc studies yielded inconsistent conclusions objective purpose meta analysis systematically analyze effect number parity gbc risk methods searched web science embase pubmed china biological medicine database inception end april 2015 studies investigating parity risk gbc included systematic review dose response meta analysis performed investigate association parity gbc risk using odds ratios 95 confidence intervals ci results thirteen case control studies eligible inclusion meta analysis including total 2 164 cases 11 340 controls significant association identified ever parity vs nulliparous 1 39 95 ci 1 15 1 68 power 0 73 2 0 0 p 0 90 similarly summary estimate high vs low parity number 1 86 95 ci 1 51 2 30 power 0 26 2 66 0 p 0 01 dose response relationship non linear association parity number gbc risk observed p non linearity 0 578 clear linear relationship detected combined odds ratio gbc increase parity one live birth 1 12 95 ci 1 09 1 21 power 0 99 2 39 9 p 0 139 subgroup sensitivity analyses showed similar associations publication bias found results significant heterogeneity subgroups detected meta regression analyses conclusions females higher parity may associated increased risk gallbladder cancer future high quality cohort studies larger sample sizes randomized controlled trials needed fully scrutinize association pubmed","probabilities":0.9799733,"Title":"Number of parity and the risk of gallbladder cancer: a systematic review and dose-response meta-analysis of observational studies","Abstract":"BACKGROUND: Current epidemiological evidence suggests an association between parity and risk of gallbladder cancer (GBC), but studies have yielded inconsistent conclusions. OBJECTIVE: The purpose of this meta-analysis is to systematically analyze the effect of the number of parity on GBC risk. METHODS: We searched Web of Science, EMBASE, PubMed, China Biological Medicine Database from inception to the end of April 2015. Studies investigating parity and risk of GBC were included. A systematic review and a dose-response meta-analysis were performed to investigate the association between parity and GBC risk using odds ratios (OR) and 95 % confidence intervals (CI). RESULTS: Thirteen case-control studies were eligible for inclusion in this meta-analysis, including a total of 2,164 cases and 11,340 controls. A significant association was identified for the ever parity vs. nulliparous at 1.39 (95 % CI 1.15-1.68; Power = 0.73; I (2) =0.0 %; P = 0.90). Similarly, the summary estimate for high vs. low parity number was 1.86 (95 % CI 1.51-2.30; Power = 0.26; I (2) = 66.0 % P < 0.01). For the dose-response relationship, a non-linear association between the parity number and GBC risk was not observed (P non-linearity = 0.578), but a clear linear relationship was detected. The combined odds ratio of GBC for an increase in parity of one live birth was 1.12 (95 % CI 1.09-1.21; Power = 0.99; I (2) = 39.9 %; P = 0.139). Subgroup and sensitivity analyses showed similar associations. No publication bias was found in all results. Significant heterogeneity between subgroups was detected by meta-regression analyses. CONCLUSIONS: In females, higher parity may be associated with an increased risk of gallbladder cancer. In the future, high-quality cohort studies with larger sample sizes and randomized controlled trials are needed to fully scrutinize this association.","Source":"PubMed","category":"HUMAN","training_data":"Number of parity and the risk of gallbladder cancer: a systematic review and dose-response meta-analysis of observational studies BACKGROUND: Current epidemiological evidence suggests an association between parity and risk of gallbladder cancer (GBC), but studies have yielded inconsistent conclusions. OBJECTIVE: The purpose of this meta-analysis is to systematically analyze the effect of the number of parity on GBC risk. METHODS: We searched Web of Science, EMBASE, PubMed, China Biological Medicine Database from inception to the end of April 2015. Studies investigating parity and risk of GBC were included. A systematic review and a dose-response meta-analysis were performed to investigate the association between parity and GBC risk using odds ratios (OR) and 95 % confidence intervals (CI). RESULTS: Thirteen case-control studies were eligible for inclusion in this meta-analysis, including a total of 2,164 cases and 11,340 controls. A significant association was identified for the ever parity vs. nulliparous at 1.39 (95 % CI 1.15-1.68; Power = 0.73; I (2) =0.0 %; P = 0.90). Similarly, the summary estimate for high vs. low parity number was 1.86 (95 % CI 1.51-2.30; Power = 0.26; I (2) = 66.0 % P < 0.01). For the dose-response relationship, a non-linear association between the parity number and GBC risk was not observed (P non-linearity = 0.578), but a clear linear relationship was detected. The combined odds ratio of GBC for an increase in parity of one live birth was 1.12 (95 % CI 1.09-1.21; Power = 0.99; I (2) = 39.9 %; P = 0.139). Subgroup and sensitivity analyses showed similar associations. No publication bias was found in all results. Significant heterogeneity between subgroups was detected by meta-regression analyses. CONCLUSIONS: In females, higher parity may be associated with an increased risk of gallbladder cancer. In the future, high-quality cohort studies with larger sample sizes and randomized controlled trials are needed to fully scrutinize this association. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surveillance cholangiocellular carcinoma cholangiocellular carcinoma frequent malignant neoplasm originating epithelium intra extrahepatic bile ducts past decades incidence cholangiocarcinoma shown increase overall mortality remained high approximate 5 year overall survival 20 surgery remains curative option systemic treatment limited palliative chemotherapy therefore surveillance strategies patients risk developing cholangiocarcinoma urgently needed particularly patients primary sclerosing cholangitis patients infected liver flukes summarize currently available data surveillance risk populations methods detection cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Surveillance in cholangiocellular carcinoma","Abstract":"Cholangiocellular carcinoma is the most frequent malignant neoplasm originating from the epithelium of intra- or extrahepatic bile ducts. In the past decades, the incidence of cholangiocarcinoma has been shown to increase while overall mortality has remained high with an approximate 5-year overall survival below 20%. Surgery remains the only curative option while systemic treatment is limited to palliative chemotherapy. Therefore, surveillance strategies for patients at risk of developing cholangiocarcinoma are urgently needed, particularly in patients with primary sclerosing cholangitis and patients infected with liver flukes. Here we summarize the currently available data on surveillance of risk populations and methods for the detection of cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Surveillance in cholangiocellular carcinoma Cholangiocellular carcinoma is the most frequent malignant neoplasm originating from the epithelium of intra- or extrahepatic bile ducts. In the past decades, the incidence of cholangiocarcinoma has been shown to increase while overall mortality has remained high with an approximate 5-year overall survival below 20%. Surgery remains the only curative option while systemic treatment is limited to palliative chemotherapy. Therefore, surveillance strategies for patients at risk of developing cholangiocarcinoma are urgently needed, particularly in patients with primary sclerosing cholangitis and patients infected with liver flukes. Here we summarize the currently available data on surveillance of risk populations and methods for the detection of cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"c24 ceramide drives gallbladder cancer progression directly targeting pip4k2c facilitate mtor signaling activation wide prevalence chemoresistance compromised early diagnosis gallbladder cancer gbc led poor patient prognosis requiring sustained efforts identification effective biomarkers novel therapeutic intervention ceramides emerged intracellular signaling molecules linked tumorigenesis therapeutic response cancers however clinical relevance ceramides gallbladder cancer investigated present study revealed aberrant gene expressions e g sptlc1 cers2 de novo ceramide biosynthesis length specific ceramide production gbc tissues analyses serum ceramide pattern healthy control gallbladder stone gbc patients identified c24 ceramide potential diagnostic biomarker patients gbc importantly elevation sptlc1 cers2 product c24 ceramide associated tumor staging distal metastasis worse prognosis line c24 ceramide promoted gbc cell proliferation migration vitro vivo mechanistically c24 ceramide directly bound pip4k2c regulator mtor facilitate mtor complex formation activation c6 ceramide analogue natural ceramide competed c24 ceramide pip4k2c binding thereby abrogating c24 ceramide mediated mtor signaling activation oncogenic activity furthermore stimulation c6 ceramide significantly suppressed proliferative metastatic capacity gbc cells vitro vivo dependent pip4k2c conclusion findings highlights clinical relevance ceramide metabolism gbc progression identify c24 ceramide novel diagnostic biomarker gbc propose pip4k2c indispensable c6 ceramide potential therapeutic intervention gbc direct competition c24 ceramide stn","probabilities":0.9467213,"Title":"C24 -Ceramide Drives Gallbladder Cancer Progression Through Directly Targeting Pip4K2C To Facilitate Mtor Signaling Activation","Abstract":"The wide prevalence of chemoresistance and compromised early diagnosis of gallbladder cancer (GBC) has led to poor patient prognosis, requiring sustained efforts for the identification of effective biomarkers and novel therapeutic intervention. Ceramides have emerged as intracellular signaling molecules linked to tumorigenesis and therapeutic response in cancers. However, the clinical relevance of ceramides with gallbladder cancer has not been investigated. In present study, we revealed aberrant gene expressions (e.g. SPTLC1 and CERS2) of de novo ceramide biosynthesis and length-specific ceramide production in GBC tissues. Analyses of serum ceramide pattern in healthy control, gallbladder stone and GBC patients identified C24-Ceramide as a potential diagnostic biomarker for patients with GBC. Importantly, elevation of SPTLC1, CERS2 and its product C24-Ceramide were associated with tumor staging, distal metastasis and worse prognosis. In line with this, C24 -Ceramide promoted GBC cell proliferation and migration in vitro and in vivo. Mechanistically, C24-Ceramide directly bound to PIP4K2C, a regulator of mTOR, to facilitate mTOR complex formation and activation. C6-Ceramide, an analogue of natural ceramide, competed with C24-Ceramide for PIP4K2C binding, thereby abrogating C24-Ceramide -mediated mTOR signaling activation and oncogenic activity. Furthermore, stimulation with C6-Ceramide significantly suppressed the proliferative and metastatic capacity of GBC cells in vitro and in vivo, which was dependent on PIP4K2C. Conclusion: Our findings highlights the clinical relevance of ceramide metabolism with GBC progression, and identify C24-Ceramide as a novel diagnostic biomarker for GBC. We propose that PIP4K2C is indispensable for C6-Ceramide as potential therapeutic intervention for GBC through a direct competition with C24-Ceramide.","Source":"STN","category":"ANIMAL","training_data":"C24 -Ceramide Drives Gallbladder Cancer Progression Through Directly Targeting Pip4K2C To Facilitate Mtor Signaling Activation The wide prevalence of chemoresistance and compromised early diagnosis of gallbladder cancer (GBC) has led to poor patient prognosis, requiring sustained efforts for the identification of effective biomarkers and novel therapeutic intervention. Ceramides have emerged as intracellular signaling molecules linked to tumorigenesis and therapeutic response in cancers. However, the clinical relevance of ceramides with gallbladder cancer has not been investigated. In present study, we revealed aberrant gene expressions (e.g. SPTLC1 and CERS2) of de novo ceramide biosynthesis and length-specific ceramide production in GBC tissues. Analyses of serum ceramide pattern in healthy control, gallbladder stone and GBC patients identified C24-Ceramide as a potential diagnostic biomarker for patients with GBC. Importantly, elevation of SPTLC1, CERS2 and its product C24-Ceramide were associated with tumor staging, distal metastasis and worse prognosis. In line with this, C24 -Ceramide promoted GBC cell proliferation and migration in vitro and in vivo. Mechanistically, C24-Ceramide directly bound to PIP4K2C, a regulator of mTOR, to facilitate mTOR complex formation and activation. C6-Ceramide, an analogue of natural ceramide, competed with C24-Ceramide for PIP4K2C binding, thereby abrogating C24-Ceramide -mediated mTOR signaling activation and oncogenic activity. Furthermore, stimulation with C6-Ceramide significantly suppressed the proliferative and metastatic capacity of GBC cells in vitro and in vivo, which was dependent on PIP4K2C. Conclusion: Our findings highlights the clinical relevance of ceramide metabolism with GBC progression, and identify C24-Ceramide as a novel diagnostic biomarker for GBC. We propose that PIP4K2C is indispensable for C6-Ceramide as potential therapeutic intervention for GBC through a direct competition with C24-Ceramide. STN","prediction_labels":"ANIMAL"},{"cleaned":"lncrna fendrr represses proliferation migration invasion suppression survivin cholangiocarcinoma cells study investigate biological function underlying mechanisms fendrr cholangiocarcinoma cca cell proliferation migration invasion fendrr survivin expression cca tissues cell lines measured qrt pcr qbc939 hucctl cells cell proliferation detected cck 8 cell migration invasion using transwell assay rna pull rip assay performed determine whether fendrr combine setdb1 cca cell effect setdb1 survivin h3k9me1 expression cca cells determined western blotting chip analysis performed analyze combination setdb1 survivin promoter cca cell effect setdb1 knockdown survivin h3k9me1 expression cca cells transfection fendrr determined western blotting results showed lncrna fendrr downregulated cca tissues cells negatively correlated survivin expression investigation demonstrated fendrr represses cca cell proliferation migration invasion regulating survivin expression fendrr associated setdb1 h3k9 epigenetically silence survivin regulated cell proliferation migration invasion findings indicate important role fendrr survivin axis cca cell proliferation migration invasion reveal novel epigenetic mechanism survivin silencing data indicated fendrr silences survivin via setdb1 mediated h3k9 methylation thereby represses cca cell proliferation migration invasion stn","probabilities":0.9467213,"Title":"Lncrna Fendrr Represses Proliferation Migration And Invasion Through Suppression Of Survivin In Cholangiocarcinoma Cells","Abstract":"This study was to investigate the biological function and underlying mechanisms of FENDRR in cholangiocarcinoma (CCA) cell proliferation, migration and invasion. FENDRR and survivin expression in CCA tissues or cell lines were measured by qRT-PCR. In QBC939 and HuCCTl cells, cell proliferation was detected by CCK-8, cell migration and invasion were using transwell assay. RNA pull-down and RIP assay were performed to determine whether FENDRR can combine with SETDB1 in CCA cell. The effect of SETDB1 on survivin and H3K9me1 expression in CCA cells were determined by western blotting. ChIP analysis was performed to analyze the combination of SETDB1 with survivin promoter in CCA cell. The effect of SETDB1 knockdown on survivin and H3K9me1 expression in CCA cells after transfection with FENDRR were determined by western blotting. The results showed that lncRNA FENDRR was downregulated in CCA tissues and cells, and was negatively correlated with survivin expression. Further investigation demonstrated that FENDRR represses CCA cell proliferation, migration and invasion through regulating survivin expression. FENDRR associated with SETDB1 and H3K9 to epigenetically silence survivin and then regulated cell proliferation, migration and invasion. These findings indicate an important role for FENDRR-survivin axis in CCA cell proliferation, migration and invasion, and reveal a novel epigenetic mechanism for survivin silencing. Our data indicated that FENDRR silences survivin via SETDB1-mediated H3K9 methylation, thereby represses CCA cell proliferation, migration and invasion.","Source":"STN","category":"ANIMAL","training_data":"Lncrna Fendrr Represses Proliferation Migration And Invasion Through Suppression Of Survivin In Cholangiocarcinoma Cells This study was to investigate the biological function and underlying mechanisms of FENDRR in cholangiocarcinoma (CCA) cell proliferation, migration and invasion. FENDRR and survivin expression in CCA tissues or cell lines were measured by qRT-PCR. In QBC939 and HuCCTl cells, cell proliferation was detected by CCK-8, cell migration and invasion were using transwell assay. RNA pull-down and RIP assay were performed to determine whether FENDRR can combine with SETDB1 in CCA cell. The effect of SETDB1 on survivin and H3K9me1 expression in CCA cells were determined by western blotting. ChIP analysis was performed to analyze the combination of SETDB1 with survivin promoter in CCA cell. The effect of SETDB1 knockdown on survivin and H3K9me1 expression in CCA cells after transfection with FENDRR were determined by western blotting. The results showed that lncRNA FENDRR was downregulated in CCA tissues and cells, and was negatively correlated with survivin expression. Further investigation demonstrated that FENDRR represses CCA cell proliferation, migration and invasion through regulating survivin expression. FENDRR associated with SETDB1 and H3K9 to epigenetically silence survivin and then regulated cell proliferation, migration and invasion. These findings indicate an important role for FENDRR-survivin axis in CCA cell proliferation, migration and invasion, and reveal a novel epigenetic mechanism for survivin silencing. Our data indicated that FENDRR silences survivin via SETDB1-mediated H3K9 methylation, thereby represses CCA cell proliferation, migration and invasion. STN","prediction_labels":"ANIMAL"},{"cleaned":"role stereotactic body radiation therapy hepatocellular carcinoma integration new technologies raised interest liver tumor radiotherapy literature evolving support efficacy advances particularly stereotactic body radiation therapy sbrt critical improving local control potential cure liver lesions amenable first line surgical resection radiofrequency ablation active investigation sbrt particularly hepatocellular carcinoma hcc recently started yielding promising local control rates addition data suggest possibility sbrt alternative option hcc unfit local therapies however information optimal treatment indications doses methods remains limited hcc significant differences patient characteristics treatment availability exist country addition prognosis hcc greatly influenced underlying liver dysfunction treatment addition tumor stage since closely linked treatment approach important understand differences interpreting outcomes various reports studies required validate maximize efficacy sbrt large multi institutional setting pubmed","probabilities":0.9799733,"Title":"Role of stereotactic body radiation therapy for hepatocellular carcinoma","Abstract":"The integration of new technologies has raised an interest in liver tumor radiotherapy, with literature evolving to support its efficacy. These advances, particularly stereotactic body radiation therapy (SBRT), have been critical in improving local control or potential cure in liver lesions not amenable to first-line surgical resection or radiofrequency ablation. Active investigation of SBRT, particularly for hepatocellular carcinoma (HCC), has recently started, yielding promising local control rates. In addition, data suggest a possibility that SBRT can be an alternative option for HCC unfit for other local therapies. However, information on optimal treatment indications, doses, and methods remains limited. In HCC, significant differences in patient characteristics and treatment availability exist by country. In addition, the prognosis of HCC is greatly influenced by underlying liver dysfunction and treatment itself in addition to tumor stage. Since they are closely linked to treatment approach, it is important to understand these differences in interpreting outcomes from various reports. Further studies are required to validate and maximize the efficacy of SBRT by a large, multi-institutional setting.","Source":"PubMed","category":"HUMAN","training_data":"Role of stereotactic body radiation therapy for hepatocellular carcinoma The integration of new technologies has raised an interest in liver tumor radiotherapy, with literature evolving to support its efficacy. These advances, particularly stereotactic body radiation therapy (SBRT), have been critical in improving local control or potential cure in liver lesions not amenable to first-line surgical resection or radiofrequency ablation. Active investigation of SBRT, particularly for hepatocellular carcinoma (HCC), has recently started, yielding promising local control rates. In addition, data suggest a possibility that SBRT can be an alternative option for HCC unfit for other local therapies. However, information on optimal treatment indications, doses, and methods remains limited. In HCC, significant differences in patient characteristics and treatment availability exist by country. In addition, the prognosis of HCC is greatly influenced by underlying liver dysfunction and treatment itself in addition to tumor stage. Since they are closely linked to treatment approach, it is important to understand these differences in interpreting outcomes from various reports. Further studies are required to validate and maximize the efficacy of SBRT by a large, multi-institutional setting. PubMed","prediction_labels":"HUMAN"},{"cleaned":"decline ca19 9 chemotherapy predicts survival four independent cohorts patients inoperable cholangiocarcinoma background carbohydrate associated antigen ca19 9 approved fda biomarker monitoring treatment effect pancreatic cancer however value serum ca19 9 biomarker response chemotherapy bile duct cancer unclear aim study determine decline ca19 9 ca19 9 response chemotherapy predictive survival patients inoperable bile duct cancer methods consecutive patients inoperable bile duct cancer treated university hospital retrospectively included investigational cohort n 212 three validation cohorts established including patients 1 participating phase ii trials danish hospital n 71 2 identified retrospectively canadian cohort n 196 3 randomized abc 02 trial n 410 patients baseline ca19 9 least one ca19 9 value measured 10 12 weeks start chemotherapy included multivariate cox regression analyses performed results patients meeting criteria included 54 investigational cohort 34 68 148 three validation sets respectively multivariate analysis included radiological response performance status bilirubin gender site cancer extend disease ca19 9 baseline age hazard ratio hr 0 60 95 ci 0 44 0 80 p 0 0005 death ca19 9 responders reached investigational cohort predictive value ca 19 9 response confirmed three validation cohorts conclusions ca19 9 response robust predictor survival patients inoperable bile duct cancer four independent data sets stn","probabilities":0.9799733,"Title":"Decline In Ca19-9 During Chemotherapy Predicts Survival In Four Independent Cohorts Of Patients With Inoperable Cholangiocarcinoma","Abstract":"Background: Carbohydrate associated antigen (CA19-9) has been approved by the FDA as a biomarker for monitoring treatment effect in pancreatic cancer. However, the value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct cancer is unclear. The aim of this study was to determine if a decline in CA19-9 (CA19-9 response) during chemotherapy is predictive of survival in patients with inoperable bile duct cancer. \r\n\r\n Methods: Consecutive patients with inoperable bile duct cancer treated at a University Hospital were retrospectively included in an investigational cohort (n = 212). Three validation cohorts were established including patients 1) participating in phase I/II trials at a Danish Hospital (n = 71), 2) identified retrospectively in a Canadian cohort (n = 196) and 3) randomized in the ABC-02 trial (n = 410). Patients with a baseline CA19-9 and at least one CA19-9 value measured 10-12 weeks after the start of chemotherapy were included. Multivariate Cox regression analyses were performed. \r\n\r\n Results: Patients meeting the criteria to be included were 54 in the investigational cohort and 34, 68 and 148 in the three validation sets, respectively. Multivariate analysis included radiological response, performance status, bilirubin, gender, site of cancer, extend of disease, CA19-9 at baseline and age. A hazard ratio (HR) of 0.60 (95%CI: 0.44-0.80, p = 0.0005) for death in CA19-9 responders was reached in the investigational cohort. The predictive value of CA 19-9 response was confirmed in all three validation cohorts. \r\n\r\n Conclusions: CA19-9 response is a robust predictor of survival in patients with inoperable bile duct cancer in four independent data sets.","Source":"STN","category":"HUMAN","training_data":"Decline In Ca19-9 During Chemotherapy Predicts Survival In Four Independent Cohorts Of Patients With Inoperable Cholangiocarcinoma Background: Carbohydrate associated antigen (CA19-9) has been approved by the FDA as a biomarker for monitoring treatment effect in pancreatic cancer. However, the value of serum CA19-9 as a biomarker of response to chemotherapy in bile duct cancer is unclear. The aim of this study was to determine if a decline in CA19-9 (CA19-9 response) during chemotherapy is predictive of survival in patients with inoperable bile duct cancer. \r\n\r\n Methods: Consecutive patients with inoperable bile duct cancer treated at a University Hospital were retrospectively included in an investigational cohort (n = 212). Three validation cohorts were established including patients 1) participating in phase I/II trials at a Danish Hospital (n = 71), 2) identified retrospectively in a Canadian cohort (n = 196) and 3) randomized in the ABC-02 trial (n = 410). Patients with a baseline CA19-9 and at least one CA19-9 value measured 10-12 weeks after the start of chemotherapy were included. Multivariate Cox regression analyses were performed. \r\n\r\n Results: Patients meeting the criteria to be included were 54 in the investigational cohort and 34, 68 and 148 in the three validation sets, respectively. Multivariate analysis included radiological response, performance status, bilirubin, gender, site of cancer, extend of disease, CA19-9 at baseline and age. A hazard ratio (HR) of 0.60 (95%CI: 0.44-0.80, p = 0.0005) for death in CA19-9 responders was reached in the investigational cohort. The predictive value of CA 19-9 response was confirmed in all three validation cohorts. \r\n\r\n Conclusions: CA19-9 response is a robust predictor of survival in patients with inoperable bile duct cancer in four independent data sets. STN","prediction_labels":"HUMAN"},{"cleaned":"molecular factors associated recurrence survival following hepatectomy patients intrahepatic cholangiocarcinoma guide adjuvant clinical trials background study sought determine clinical molecular factors related recurrence survival patients icc following hepatectomy methods database review identified 34 patients molecular markers ki67 p53 beta catenin standard pathological evaluations performed results common resections right n 11 extended right n 8 left hepatectomy n 7 30 90 day mortality rates 5 9 11 8 median tumor size 7 8 cm nine patients 26 5 positive lymph nodes ten patients 29 4 received adjuvant therapy median follow 33 5 months median disease free interval 6 months median overall survival 37 9 months univariate predictors recurrence tumor size p 0 02 differentiation p 0 05 multivariate analysis differentiation p 0 03 0 38 95 ci 0 17 0 89 remained significant univariate predictors survival tumor size p 0 02 lymphovascular invasion p 0 02 satellite nodules p 0 006 beta catenin expression p 0 008 recurrence p 0 026 multivariate analyses satellite lesions p 0 05 3 15 95 ci 0 96 10 4 beta catenin p 0 04 3 23 95 ci 1 1 9 7 remained significant differentiation p 0 045 0 42 95 ci 0 18 0 98 additional predictor conclusion future clinical trials include certain molecular pathologic factors assist determining necessity type adjuvant therapy pubmed","probabilities":0.9799733,"Title":"Molecular factors associated with recurrence and survival following hepatectomy in patients with intrahepatic cholangiocarcinoma: a guide to adjuvant clinical trials","Abstract":"BACKGROUND: This study sought to determine clinical and molecular factors related to recurrence and survival in patients with ICC following hepatectomy. METHODS: Database review identified 34 patients. Molecular markers (Ki67, p53, beta-catenin) and standard pathological evaluations were performed. RESULTS: The most common resections were right (n = 11), extended right (n = 8), and left hepatectomy (n = 7). The 30- and 90 -day mortality rates were 5.9% and 11.8%. The median tumor size was 7.8 cm. Nine patients (26.5%) had positive lymph nodes and ten patients (29.4%) received adjuvant therapy. Median follow up was 33.5 months. The median disease-free interval was 6 months. The median overall survival was 37.9 months. Univariate predictors of recurrence were tumor size (P = 0.02) and differentiation (P = 0.05). On multivariate analysis, differentiation (P = 0.03; OR = 0.38; 95% CI: 0.17-0.89) remained significant. Univariate predictors of survival were tumor size (P = 0.02), lymphovascular invasion (P = 0.02), satellite nodules (P = 0.006), beta-catenin expression (P = 0.008), and recurrence (P = 0.026). On multivariate analyses, satellite lesions (P = 0.05, OR = 3.15, 95% CI: 0.96-10.4) and beta-catenin (P = 0.04, OR = 3.23; 95% CI: 1.1-9.7) remained significant and differentiation (P = 0.045; OR = 0.42; 95% CI: 0.18-0.98) was an additional predictor. CONCLUSION: Future clinical trials could include certain molecular and pathologic factors to assist in determining the necessity and type of adjuvant therapy.","Source":"PubMed","category":"HUMAN","training_data":"Molecular factors associated with recurrence and survival following hepatectomy in patients with intrahepatic cholangiocarcinoma: a guide to adjuvant clinical trials BACKGROUND: This study sought to determine clinical and molecular factors related to recurrence and survival in patients with ICC following hepatectomy. METHODS: Database review identified 34 patients. Molecular markers (Ki67, p53, beta-catenin) and standard pathological evaluations were performed. RESULTS: The most common resections were right (n = 11), extended right (n = 8), and left hepatectomy (n = 7). The 30- and 90 -day mortality rates were 5.9% and 11.8%. The median tumor size was 7.8 cm. Nine patients (26.5%) had positive lymph nodes and ten patients (29.4%) received adjuvant therapy. Median follow up was 33.5 months. The median disease-free interval was 6 months. The median overall survival was 37.9 months. Univariate predictors of recurrence were tumor size (P = 0.02) and differentiation (P = 0.05). On multivariate analysis, differentiation (P = 0.03; OR = 0.38; 95% CI: 0.17-0.89) remained significant. Univariate predictors of survival were tumor size (P = 0.02), lymphovascular invasion (P = 0.02), satellite nodules (P = 0.006), beta-catenin expression (P = 0.008), and recurrence (P = 0.026). On multivariate analyses, satellite lesions (P = 0.05, OR = 3.15, 95% CI: 0.96-10.4) and beta-catenin (P = 0.04, OR = 3.23; 95% CI: 1.1-9.7) remained significant and differentiation (P = 0.045; OR = 0.42; 95% CI: 0.18-0.98) was an additional predictor. CONCLUSION: Future clinical trials could include certain molecular and pathologic factors to assist in determining the necessity and type of adjuvant therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact prediction lymph node involvement patients intrahepatic cholangiocarcinoma curative resection background aim study identify preoperative predictors prognosis patients intrahepatic cholangiocarcinoma icc undergoing resection patients methods enrolled 90 patients icc underwent surgical resection including 59 surgery considered curative measured overall survival os recurrence free survival rfs outcomes potential prognostic factors results multivariate cox proportional hazards analysis showed tumor resection margins r 0 independently predicted long term os whole cohort curatively resected group r0 lymph node involvement independent predictor long term os multiple tumors perihilar tumor location serum carcinoembryonic antigen cea concentration 2 2 ng ml independent predictors lymph node involvement curative resection conclusion patients icc multiple tumors perihilar tumors serum cea concentration 2 2 ng ml association lymph node involvement may need additional preoperative chemotherapy pubmed","probabilities":0.9799733,"Title":"Impact and Prediction of Lymph Node Involvement in Patients with Intrahepatic Cholangiocarcinoma After Curative Resection","Abstract":"BACKGROUND: The aim of this study was to identify the preoperative predictors of prognosis in patients with intrahepatic cholangiocarcinoma (ICC) undergoing resection. PATIENTS AND METHODS: We enrolled 90 patients with ICC who underwent surgical resection, including 59 in whom surgery was considered curative, and measured the overall survival (OS), recurrence-free survival (RFS), and other outcomes and potential prognostic factors. RESULTS: Multivariate Cox proportional hazards analysis showed that tumor in the resection margins (R>0) independently predicted long-term OS in the whole cohort. In the curatively-resected group (R0), lymph node involvement was the only independent predictor of long-term OS. Multiple tumors, perihilar tumor location and serum carcinoembryonic antigen (CEA) concentration >2.2 ng/ml were independent predictors of lymph node involvement before curative resection. CONCLUSION: Patients with ICC with multiple tumors, perihilar tumors and serum CEA concentration >2.2 ng/ml in association with lymph node involvement may need additional preoperative chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Impact and Prediction of Lymph Node Involvement in Patients with Intrahepatic Cholangiocarcinoma After Curative Resection BACKGROUND: The aim of this study was to identify the preoperative predictors of prognosis in patients with intrahepatic cholangiocarcinoma (ICC) undergoing resection. PATIENTS AND METHODS: We enrolled 90 patients with ICC who underwent surgical resection, including 59 in whom surgery was considered curative, and measured the overall survival (OS), recurrence-free survival (RFS), and other outcomes and potential prognostic factors. RESULTS: Multivariate Cox proportional hazards analysis showed that tumor in the resection margins (R>0) independently predicted long-term OS in the whole cohort. In the curatively-resected group (R0), lymph node involvement was the only independent predictor of long-term OS. Multiple tumors, perihilar tumor location and serum carcinoembryonic antigen (CEA) concentration >2.2 ng/ml were independent predictors of lymph node involvement before curative resection. CONCLUSION: Patients with ICC with multiple tumors, perihilar tumors and serum CEA concentration >2.2 ng/ml in association with lymph node involvement may need additional preoperative chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact initial postoperative ca19 9 level patients extrahepatic bile duct cancer background aim study investigate prognostic impact initial serum postoperative ca19 9 levels patients extrahepatic bile duct cancer methods data total 143 patients extrahepatic bile duct cancer elevated preoperative serum ca19 9 levels 37 u ml underwent surgery curative intent reviewed retrospectively patients divided normalization group non normalization group initial postoperative serum ca19 9 37 37 u ml respectively clinicopathological factors survival outcomes groups comparatively analyzed results cumulative 5 year overall survival os rate median survival time mst 39 2 42 9 months respectively normalization group 17 9 24 0 months respectively non normalization group p 0 001 presence jaundice poorer histological differentiation grade g3 4 lymph node metastasis initial postoperative serum ca19 9 level 37 u ml significant independent predictors poor prognosis multivariate analysis conclusion non normalization serum ca19 9 level initial postoperative phase strong predictor poor prognosis useful marker identify patients need additional treatments stricter follow pubmed","probabilities":0.9799733,"Title":"Prognostic Impact of the Initial Postoperative CA19-9 Level in Patients with Extrahepatic Bile Duct Cancer","Abstract":"BACKGROUND: The aim of this study was to investigate the prognostic impact of the initial serum postoperative CA19-9 levels in patients with extrahepatic bile duct cancer. METHODS: Data of a total of 143 patients of extrahepatic bile duct cancer with elevated preoperative serum CA19-9 levels (>37 U/ml) who underwent surgery with curative intent were reviewed retrospectively. The patients were divided into the \"Normalization group\" and \"Non-normalization group\" (initial postoperative serum CA19-9 ≤37 and >37 U/ml, respectively), and the clinicopathological factors and survival outcomes in these groups were comparatively analyzed. RESULTS: The cumulative 5-year overall survival (OS) rate and median survival time (MST) were 39.2 % and 42.9 months, respectively, in the Normalization group and 17.9 % and 24.0 months, respectively, in the Non-normalization group (P < 0.001). Presence of jaundice, a poorer histological differentiation grade (G3-4), lymph node metastasis, and initial postoperative serum CA19-9 level (>37 U/ml) were significant independent predictors of a poor prognosis on multivariate analysis. CONCLUSION: Non-normalization of the serum CA19-9 level in the initial postoperative phase is a strong predictor of a poor prognosis and is a useful marker to identify patients who would need additional treatments and stricter follow-up.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Impact of the Initial Postoperative CA19-9 Level in Patients with Extrahepatic Bile Duct Cancer BACKGROUND: The aim of this study was to investigate the prognostic impact of the initial serum postoperative CA19-9 levels in patients with extrahepatic bile duct cancer. METHODS: Data of a total of 143 patients of extrahepatic bile duct cancer with elevated preoperative serum CA19-9 levels (>37 U/ml) who underwent surgery with curative intent were reviewed retrospectively. The patients were divided into the \"Normalization group\" and \"Non-normalization group\" (initial postoperative serum CA19-9 ≤37 and >37 U/ml, respectively), and the clinicopathological factors and survival outcomes in these groups were comparatively analyzed. RESULTS: The cumulative 5-year overall survival (OS) rate and median survival time (MST) were 39.2 % and 42.9 months, respectively, in the Normalization group and 17.9 % and 24.0 months, respectively, in the Non-normalization group (P < 0.001). Presence of jaundice, a poorer histological differentiation grade (G3-4), lymph node metastasis, and initial postoperative serum CA19-9 level (>37 U/ml) were significant independent predictors of a poor prognosis on multivariate analysis. CONCLUSION: Non-normalization of the serum CA19-9 level in the initial postoperative phase is a strong predictor of a poor prognosis and is a useful marker to identify patients who would need additional treatments and stricter follow-up. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact radiotherapy management locally advanced extrahepatic cholangiocarcinoma background optimal therapy patients unresectable locally advanced extrahepatic cholangiocarcinoma ulac remains controversial analysed role radiotherapy management tumors methods retrospectively reviewed charts patients treated institution conformal 3d external beam radiotherapy ebrt without concurrent chemotherapy results thirty patients included 24 primary tumor group 1 6 local relapse group 2 toxicity low among 25 patients assessable ebrt response observed 9 complete responses 4 partial responses 10 stabilisations 2 progressions median follow 12 months twenty 30 patients 66 experienced relapse metastatic 75 cases whole series 87 group 1 60 group 2 p 0 25 twenty eight patients 93 died relapse disease complications median overall survivals whole group group 1 2 respectively 12 11 21 months p 0 11 1 year 3 year progression free survivals respectively 38 16 whole series 31 11 group 1 67 33 group 2 p 0 35 conclusion ebrt seems efficient treat ulac acceptable toxicity primary disease high rate metastatic relapse suggests limit ebrt non progressive patients induction chemotherapy pubmed","probabilities":0.9799733,"Title":"Impact of radiotherapy in the management of locally advanced extrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Optimal therapy for patients with unresectable locally advanced extrahepatic cholangiocarcinoma (ULAC) remains controversial. We analysed the role of radiotherapy in the management of such tumors. METHODS: We retrospectively reviewed the charts of patients treated in our institution with conformal-3D external-beam-radiotherapy (EBRT) with or without concurrent chemotherapy. RESULTS: Thirty patients were included: 24 with a primary tumor (group 1) and 6 with a local relapse (group 2). Toxicity was low. Among 25 patients assessable for EBRT response, we observed 9 complete responses, 4 partial responses, 10 stabilisations, and 2 progressions. The median follow-up was 12 months. Twenty out of 30 patients (66%) experienced a relapse, which was metastatic in 75% of cases in the whole series, 87% in group 1, 60% in group 2 (p = 0.25). Twenty-eight patients (93%) died of relapse or disease complications. Median overall survivals in the whole group and in group 1 or 2 were respectively 12, 11 and 21 months (p = 0.11). The 1-year and 3-year progression-free survivals were respectively 38% and 16% in the whole series; 31% and 11% in group 1, 67% and 33% in group 2 (p = 0.35). CONCLUSION: EBRT seems efficient to treat ULAC, with acceptable toxicity. For primary disease, the high rate of metastatic relapse suggests to limit EBRT to non-progressive patients after induction chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Impact of radiotherapy in the management of locally advanced extrahepatic cholangiocarcinoma BACKGROUND: Optimal therapy for patients with unresectable locally advanced extrahepatic cholangiocarcinoma (ULAC) remains controversial. We analysed the role of radiotherapy in the management of such tumors. METHODS: We retrospectively reviewed the charts of patients treated in our institution with conformal-3D external-beam-radiotherapy (EBRT) with or without concurrent chemotherapy. RESULTS: Thirty patients were included: 24 with a primary tumor (group 1) and 6 with a local relapse (group 2). Toxicity was low. Among 25 patients assessable for EBRT response, we observed 9 complete responses, 4 partial responses, 10 stabilisations, and 2 progressions. The median follow-up was 12 months. Twenty out of 30 patients (66%) experienced a relapse, which was metastatic in 75% of cases in the whole series, 87% in group 1, 60% in group 2 (p = 0.25). Twenty-eight patients (93%) died of relapse or disease complications. Median overall survivals in the whole group and in group 1 or 2 were respectively 12, 11 and 21 months (p = 0.11). The 1-year and 3-year progression-free survivals were respectively 38% and 16% in the whole series; 31% and 11% in group 1, 67% and 33% in group 2 (p = 0.35). CONCLUSION: EBRT seems efficient to treat ULAC, with acceptable toxicity. For primary disease, the high rate of metastatic relapse suggests to limit EBRT to non-progressive patients after induction chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"perioperative transfusion indicator poor prognosis surgical resection hilar cholangiocarcinoma introduction surgery potentially curative treatment hilar cholangiocarcinoma recent progress surgical techniques hilar cholangiocarcinoma led improved outcomes aggressive liver bile duct resections however still show considerable morbidity poor prognosis study assessed prognostic indicators longterm survival surgical resection hilar cholangiocarcinoma method sixty one consecutive hepatectomies en bloc resection caudate lobe extrahepatic bile duct hilar cholangiocarcinoma performed institute 2004 2012 twenty four clinicopathologic factors recurrence survival retrospectively assessed univariate kaplan meier curves log rank test multivariate analyses cox proportional hazards model results surgical morbidity clavien grades iii v mortality rates 49 2 respectively results univariate analysis showed male preoperative jaundice elevated level serum ca19 9 preoperative portal vein embolization right hepatectomy perioperative transfusion postoperative morbidity postoperative hyperbilirubinemia lymphnode metastasis major vascular invasion microvascular invasion lymphovascular invasion histological positive margin found signi cant prognostic factors recurrence survival p 0 05 multivariate analysis revealed perioperative transfusion independently associated recurrence hr 4 38 95 ci 1 89 10 03 p 0 001 survival hr 3 19 95 ci 1 23 8 27 p 0 017 conclusions perioperative transfusion strong predictor poor survival radical hepatectomy hilar cholangiocarcinoma suggest circumventing perioperative transfusion plays important role long term survival patients hilar cholangiocarcinoma google scholar","probabilities":0.9799733,"Title":"Perioperative Transfusion As An Indicator For Poor Prognosis After Surgical Resection For Hilar Cholangiocarcinoma","Abstract":"Introduction: Surgery is the only potentially curative treatment for hilar cholangiocarcinoma. Recent progress in surgical techniques for hilar cholangiocarcinoma has led to improved outcomes for aggressive liver and bile duct resections, which, however, still show considerable morbidity and poor prognosis. In this study, we assessed the prognostic indicators for longterm survival after surgical resection for hilar cholangiocarcinoma. Method: Sixty-one consecutive hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile duct for hilar cholangiocarcinoma were performed at our institute from 2004 to 2012. Twenty-four clinicopathologic factors for recurrence and survival were retrospectively assessed by univariate (Kaplan-Meier curves and log-rank test) and multivariate analyses (Cox proportional hazards model). Results: The surgical morbidity (Clavien grades III–V) and mortality rates were 49% and 2%, respectively. Results of univariate analysis showed that male, preoperative jaundice, elevated level of serum CA19-9, preoperative portal vein embolization, right hepatectomy, perioperative transfusion, postoperative morbidity, postoperative hyperbilirubinemia, lymphnode metastasis, major vascular invasion, microvascular invasion, lymphovascular invasion, and histological positive margin were found to be significant prognostic factors for both recurrence and survival (p < 0.05). Multivariate analysis revealed that the only perioperative transfusion was independently associated with both recurrence (HR=4.38, 95% CI 1.89–10.03, p = 0.001) and survival (HR=3.19, 95% CI 1.23–8.27, p = 0.017). Conclusions: Perioperative transfusion was a strong predictor for poor survival after radical hepatectomy for hilar cholangiocarcinoma. We suggest that circumventing perioperative transfusion plays an important role in long-term survival for the patients with hilar cholangiocarcinoma.","Source":"Google Scholar","category":"HUMAN","training_data":"Perioperative Transfusion As An Indicator For Poor Prognosis After Surgical Resection For Hilar Cholangiocarcinoma Introduction: Surgery is the only potentially curative treatment for hilar cholangiocarcinoma. Recent progress in surgical techniques for hilar cholangiocarcinoma has led to improved outcomes for aggressive liver and bile duct resections, which, however, still show considerable morbidity and poor prognosis. In this study, we assessed the prognostic indicators for longterm survival after surgical resection for hilar cholangiocarcinoma. Method: Sixty-one consecutive hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile duct for hilar cholangiocarcinoma were performed at our institute from 2004 to 2012. Twenty-four clinicopathologic factors for recurrence and survival were retrospectively assessed by univariate (Kaplan-Meier curves and log-rank test) and multivariate analyses (Cox proportional hazards model). Results: The surgical morbidity (Clavien grades III–V) and mortality rates were 49% and 2%, respectively. Results of univariate analysis showed that male, preoperative jaundice, elevated level of serum CA19-9, preoperative portal vein embolization, right hepatectomy, perioperative transfusion, postoperative morbidity, postoperative hyperbilirubinemia, lymphnode metastasis, major vascular invasion, microvascular invasion, lymphovascular invasion, and histological positive margin were found to be significant prognostic factors for both recurrence and survival (p < 0.05). Multivariate analysis revealed that the only perioperative transfusion was independently associated with both recurrence (HR=4.38, 95% CI 1.89–10.03, p = 0.001) and survival (HR=3.19, 95% CI 1.23–8.27, p = 0.017). Conclusions: Perioperative transfusion was a strong predictor for poor survival after radical hepatectomy for hilar cholangiocarcinoma. We suggest that circumventing perioperative transfusion plays an important role in long-term survival for the patients with hilar cholangiocarcinoma. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"genetic epigenetic alterations riz1 correlation clinicopathological parameters liver fluke related cholangiocarcinoma retinoblastoma interacting zinc finger riz1 gene adjacent d1s228 microsatellite instability associated poor patient survival liver fluke associated cholangiocarcinoma cca understanding molecular mechanisms underlying carcinogenesis pathogenesis cca necessary improve patient survival therefore determined genetic epigenetic alterations riz1 81 cca samples 69 matched non tumor tissues methylation found 31 81 38 tumor samples 5 69 7 matched non tumor tissues frameshift mutations 2 81 loss heterozygosity loh 14 81 common statistical analysis found significant correlation riz1 alterations clinicopathological features rizpro704 loh associated patient survival multivariate analysis riz1 hypermethylation may one crucial molecular events contributing cholangiocarcinogenesis rizpro704 loh may adversely impact patient survival biological function riz1 cca investigated order verify potential role regulating cancer stn","probabilities":0.9285714,"Title":"Genetic And Epigenetic Alterations Of Riz1 And The Correlation To Clinicopathological Parameters In Liver Fluke-Related Cholangiocarcinoma","Abstract":"The retinoblastoma interacting zinc finger (RIZ1) gene is adjacent to D1S228 where microsatellite instability has been associated with poor patient survival in liver fluke-associated cholangiocarcinoma (CCA). An understanding of the molecular mechanisms underlying the carcinogenesis and pathogenesis of CCA is necessary to improve patient survival. Therefore, we determined the genetic and epigenetic alterations of RIZ1 in 81 CCA samples and 69 matched non-tumor tissues. Methylation was found in 31 of 81 (38%) tumor samples and in 5 of 69 (7%) matched non-tumor tissues. Frameshift mutations (2 of 81) and loss of heterozygosity (LOH) (14 of 81) were not common. Statistical analysis found no significant correlation between RIZ1 alterations and clinicopathological features, but RIZPro704 LOH was associated with patient survival in the multivariate analysis. RIZ1 hypermethylation may be one of the crucial molecular events contributing to cholangiocarcinogenesis, and RIZPro704 LOH may adversely impact patient survival. The biological function of RIZ1 in CCA should be further investigated in order to verify its potential role in regulating this cancer.","Source":"STN","category":"ANIMAL","training_data":"Genetic And Epigenetic Alterations Of Riz1 And The Correlation To Clinicopathological Parameters In Liver Fluke-Related Cholangiocarcinoma The retinoblastoma interacting zinc finger (RIZ1) gene is adjacent to D1S228 where microsatellite instability has been associated with poor patient survival in liver fluke-associated cholangiocarcinoma (CCA). An understanding of the molecular mechanisms underlying the carcinogenesis and pathogenesis of CCA is necessary to improve patient survival. Therefore, we determined the genetic and epigenetic alterations of RIZ1 in 81 CCA samples and 69 matched non-tumor tissues. Methylation was found in 31 of 81 (38%) tumor samples and in 5 of 69 (7%) matched non-tumor tissues. Frameshift mutations (2 of 81) and loss of heterozygosity (LOH) (14 of 81) were not common. Statistical analysis found no significant correlation between RIZ1 alterations and clinicopathological features, but RIZPro704 LOH was associated with patient survival in the multivariate analysis. RIZ1 hypermethylation may be one of the crucial molecular events contributing to cholangiocarcinogenesis, and RIZPro704 LOH may adversely impact patient survival. The biological function of RIZ1 in CCA should be further investigated in order to verify its potential role in regulating this cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"clinical significance isolated biliary candidiasis patients unresectable cholangiocarcinoma background frequency isolated biliary candidiasis increasing cancer patients clinical significance isolated biliary candidiasis remains unclear analyzed risk factors biliary candidiasis outcomes patients unresectable cholangiocarcinoma percutaneous transhepatic biliary drainage ptbd methods among 430 patients underwent ptbd january 2012 march 2015 121 patients unresectable cholangiocarcinoma bile blood samples collected consecutive fungal culture results study cohort included 49 women 72 men median age 71 years multivariate analysis showed cancer progression p 0 013 concurrent presence another microorganism p 0 010 previous long term 7 days antibiotic use p 0 011 potential risk factors biliary candidiasis chemotherapy associated overall biliary candidiasis p 0 196 significantly related repeated biliary candidiasis p 0 011 patients isolated biliary candidiasis showed remarkably reduced survival compared without median overall survival os 32 vs 62 days p 0 011 subgroup analysis also performed patients repeated candidiasis markedly decreased survival compared transient candidiasis median os 30 vs 49 days p 0 046 biliary candidiasis identified poor prognostic factor univariate multivariate analyses p 0 033 four cases repeated candidiasis 4 19 21 showed candida species consecutive blood culture end study others showed candidemia conclusions isolated biliary candidiasis may associated poor prognosis patients unresectable cholangiocarcinoma especially repeated biliary candidiasis may possibility progression candidemia suggest biliary dilatation treatment antifungal agents might helpful patients biliary candidiasis pubmed","probabilities":0.9799733,"Title":"Clinical significance of isolated biliary candidiasis in patients with unresectable cholangiocarcinoma","Abstract":"BACKGROUND: The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical significance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasis and outcomes of the patients with unresectable cholangiocarcinoma after percutaneous transhepatic biliary drainage (PTBD). METHODS: Among 430 patients who underwent PTBD between January 2012 and March 2015, 121 patients had unresectable cholangiocarcinoma. Bile and blood samples were collected for consecutive fungal culture. RESULTS: The study cohort included 49 women and 72 men with a median age of 71 years. Multivariate analysis showed that cancer progression (P=0.013), concurrent presence of another microorganism (P=0.010), and previous long-term (>7 days) antibiotic use (P=0.011) were potential risk factors of biliary candidiasis. Chemotherapy was not associated with overall biliary candidiasis (P=0.196), but was significantly related to repeated biliary candidiasis (P=0.011). Patients with isolated biliary candidiasis showed remarkably reduced survival compared with those without [median overall survival (OS): 32 vs 62 days, P=0.011]. Subgroup analysis was also performed. Patients with repeated candidiasis had markedly decreased survival compared with those with transient candidiasis (median OS: 30 vs 49 days, P=0.046). Biliary candidiasis was identified as a poor prognostic factor by univariate and multivariate analyses (P=0.033). Four cases of repeated candidiasis (4/19, 21%) showed Candida species in consecutive blood culture until the end of the study, but others showed no candidemia. CONCLUSIONS: Isolated biliary candidiasis may be associated with poor prognosis in patients with unresectable cholangiocarcinoma. Especially, repeated biliary candidiasis may have the possibility of progression to candidemia. We suggest that biliary dilatation treatment or antifungal agents might be helpful for patients with biliary candidiasis.","Source":"PubMed","category":"HUMAN","training_data":"Clinical significance of isolated biliary candidiasis in patients with unresectable cholangiocarcinoma BACKGROUND: The frequency of isolated biliary candidiasis is increasing in cancer patients. The clinical significance of isolated biliary candidiasis remains unclear. We analyzed the risk factors of biliary candidiasis and outcomes of the patients with unresectable cholangiocarcinoma after percutaneous transhepatic biliary drainage (PTBD). METHODS: Among 430 patients who underwent PTBD between January 2012 and March 2015, 121 patients had unresectable cholangiocarcinoma. Bile and blood samples were collected for consecutive fungal culture. RESULTS: The study cohort included 49 women and 72 men with a median age of 71 years. Multivariate analysis showed that cancer progression (P=0.013), concurrent presence of another microorganism (P=0.010), and previous long-term (>7 days) antibiotic use (P=0.011) were potential risk factors of biliary candidiasis. Chemotherapy was not associated with overall biliary candidiasis (P=0.196), but was significantly related to repeated biliary candidiasis (P=0.011). Patients with isolated biliary candidiasis showed remarkably reduced survival compared with those without [median overall survival (OS): 32 vs 62 days, P=0.011]. Subgroup analysis was also performed. Patients with repeated candidiasis had markedly decreased survival compared with those with transient candidiasis (median OS: 30 vs 49 days, P=0.046). Biliary candidiasis was identified as a poor prognostic factor by univariate and multivariate analyses (P=0.033). Four cases of repeated candidiasis (4/19, 21%) showed Candida species in consecutive blood culture until the end of the study, but others showed no candidemia. CONCLUSIONS: Isolated biliary candidiasis may be associated with poor prognosis in patients with unresectable cholangiocarcinoma. Especially, repeated biliary candidiasis may have the possibility of progression to candidemia. We suggest that biliary dilatation treatment or antifungal agents might be helpful for patients with biliary candidiasis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"lncrna linc01061 sponges mir 612 regulate oncogenic role sema4d cholangiocarcinoma cholangiocarcinoma cca usual malignancy biliary tract possessing relatively low overall survival rate due limited treatment options recently long non coding rnas lncrnas testified marked regulatory impacts human cancers purpose paper explore potent regulation mechanism linc01061 involved cca firstly observed linc01061 expression heightened cca cell lines whose knockdown suppressed cell proliferation induced cell apoptosis restrained cell migration besides linc01061 existing cytoplasm cca cells interacted mir 612 moreover subsequent experiments affirmed linc01061 regulated sema4d expression acting competing endogenous rna cerna mir 612 last rescue assays validated sema4d overexpression restored repression caused linc01061 silence biological activities cca containing cell proliferation apoptosis migration sum present exploration demonstrated linc01061 sponges mir 612 upregulate sema4d expression progression cca suggesting optional promising effective target therapy patients cca stn","probabilities":0.9467213,"Title":"Lncrna Linc01061 Sponges Mir-612 To Regulate The Oncogenic Role Of Sema4D In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is the most usual malignancy of biliary tract, possessing a relatively low overall survival rate due to limited treatment options. Recently, long non-coding RNAs (lncRNAs) have been testified to have marked regulatory impacts on human cancers. The purpose of this paper is to explore the potent regulation mechanism of LINC01061 involved in CCA. Firstly, it was observed that LINC01061 expression was heightened in CCA cell lines, whose knockdown suppressed cell proliferation, induced cell apoptosis and restrained cell migration. Besides, LINC01061 existing in the cytoplasm of CCA cells interacted with miR-612. Moreover, subsequent experiments affirmed that LINC01061 regulated SEMA4D expression by acting as a competing endogenous RNA (ceRNA) of miR-612. At last, rescue assays validated that SEMA4D overexpression restored the repression caused by LINC01061 silence on the biological activities of CCA containing cell proliferation, apoptosis and migration. To sum up, our present exploration demonstrated that LINC01061 sponges miR-612 so as to upregulate SEMA4D expression for the progression of CCA, suggesting an optional promising and effective target for the therapy of patients with CCA.","Source":"STN","category":"ANIMAL","training_data":"Lncrna Linc01061 Sponges Mir-612 To Regulate The Oncogenic Role Of Sema4D In Cholangiocarcinoma Cholangiocarcinoma (CCA) is the most usual malignancy of biliary tract, possessing a relatively low overall survival rate due to limited treatment options. Recently, long non-coding RNAs (lncRNAs) have been testified to have marked regulatory impacts on human cancers. The purpose of this paper is to explore the potent regulation mechanism of LINC01061 involved in CCA. Firstly, it was observed that LINC01061 expression was heightened in CCA cell lines, whose knockdown suppressed cell proliferation, induced cell apoptosis and restrained cell migration. Besides, LINC01061 existing in the cytoplasm of CCA cells interacted with miR-612. Moreover, subsequent experiments affirmed that LINC01061 regulated SEMA4D expression by acting as a competing endogenous RNA (ceRNA) of miR-612. At last, rescue assays validated that SEMA4D overexpression restored the repression caused by LINC01061 silence on the biological activities of CCA containing cell proliferation, apoptosis and migration. To sum up, our present exploration demonstrated that LINC01061 sponges miR-612 so as to upregulate SEMA4D expression for the progression of CCA, suggesting an optional promising and effective target for the therapy of patients with CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"comparison resection transarterial chemoembolisation treatment advanced intrahepatic cholangiocarcinoma single center experience aims aim study evaluate factors associated outcome surgical resection compare efficacy surgery transarterial chemoembolisation tace patients advanced intrahepatic cholangiocarcinoma ihc materials methods 273 patients ihc treated department 1997 2012 included study patients divided according therapy surgical n 130 tace n 32 systemic chemotherapy best supportive care n 111 groups clinicopathological characteristics survival reviewed retrospectively results 1 3 5 year survival rates patients surgical resection 60 40 23 respectively recurrence occurred 63 percent patients r0 resection median time recurrence free survival 14 months univariate analysis revealed nine significant risk factors overall survival resection group major surgery extrahepatic resection vascular bile duct resection lymph node invasion poor tumour differentiation positive surgical margin multiple lesions tumour diameter uicc stage multivariate analysis showed lymph node metastasis p 0 001 poor tumour differentiation p 0 002 positive resection margins p 0 001 independent prognostic factors survival median survival well overall survival rates tace patients comparable lymph node positive patients patients tumour positive surgical margins conclusions r0 resection patients negative lymph node status remains best chance long term survival patients ihc significant survival benefit surgery lymph node positive patients patients positive resection margin tace pubmed","probabilities":0.9799733,"Title":"Comparison of resection and transarterial chemoembolisation in the treatment of advanced intrahepatic cholangiocarcinoma--a single-center experience","Abstract":"AIMS: The aim of this study is to evaluate factors associated with the outcome after surgical resection and to compare the efficacy of surgery to transarterial chemoembolisation (TACE) in patients with advanced intrahepatic cholangiocarcinoma (IHC). MATERIALS AND METHODS: 273 patients with IHC treated in our department between 1997 and 2012 were included in our study. Patients were divided according to therapy into surgical (n = 130), TACE (n = 32), and systemic chemotherapy/best supportive care (n = 111) groups. Clinicopathological characteristics and survival were reviewed retrospectively. RESULTS: The 1-, 3-, and 5-year survival rates in patients after surgical resection were 60%, 40%, and 23%, respectively. Recurrence occurred in 63 percent of patients after R0 resection. Median time of recurrence-free survival was 14 months. Univariate analysis revealed nine significant risk factors for overall survival in the resection group: major surgery, extrahepatic resection, vascular and bile duct resection, lymph node invasion, poor tumour differentiation, positive surgical margin, multiple lesions, tumour diameter, and UICC-Stage. Multivariate analysis showed that lymph node metastasis (P < 0.001), poor tumour differentiation (P = 0.002), and positive resection margins (P = 0.001) were independent prognostic factors for survival. Median survival as well as overall survival rates of TACE patients were comparable to those of lymph node positive patients and patients with tumour positive surgical margins. CONCLUSIONS: R0 resection in patients with negative lymph node status remains the best chance for long-term survival in patients with IHC. There is no significant survival benefit of surgery in lymph node positive patients or patients with positive resection margin over TACE.","Source":"PubMed","category":"HUMAN","training_data":"Comparison of resection and transarterial chemoembolisation in the treatment of advanced intrahepatic cholangiocarcinoma--a single-center experience AIMS: The aim of this study is to evaluate factors associated with the outcome after surgical resection and to compare the efficacy of surgery to transarterial chemoembolisation (TACE) in patients with advanced intrahepatic cholangiocarcinoma (IHC). MATERIALS AND METHODS: 273 patients with IHC treated in our department between 1997 and 2012 were included in our study. Patients were divided according to therapy into surgical (n = 130), TACE (n = 32), and systemic chemotherapy/best supportive care (n = 111) groups. Clinicopathological characteristics and survival were reviewed retrospectively. RESULTS: The 1-, 3-, and 5-year survival rates in patients after surgical resection were 60%, 40%, and 23%, respectively. Recurrence occurred in 63 percent of patients after R0 resection. Median time of recurrence-free survival was 14 months. Univariate analysis revealed nine significant risk factors for overall survival in the resection group: major surgery, extrahepatic resection, vascular and bile duct resection, lymph node invasion, poor tumour differentiation, positive surgical margin, multiple lesions, tumour diameter, and UICC-Stage. Multivariate analysis showed that lymph node metastasis (P < 0.001), poor tumour differentiation (P = 0.002), and positive resection margins (P = 0.001) were independent prognostic factors for survival. Median survival as well as overall survival rates of TACE patients were comparable to those of lymph node positive patients and patients with tumour positive surgical margins. CONCLUSIONS: R0 resection in patients with negative lymph node status remains the best chance for long-term survival in patients with IHC. There is no significant survival benefit of surgery in lymph node positive patients or patients with positive resection margin over TACE. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cancer surveillance patients primary sclerosing cholangitis primary sclerosing cholangitis psc chronic fibroinflammatory syndrome involving biliary tract often accompanied inflammatory bowel disease ibd syndrome prototype disease linking chronic inflammation carcinogenesis indeed psc associated increased risk cholangiocarcinoma cca gallbladder cancer hepatocellular carcinoma hcc colorectal cancer herein review risk malignancies psc discuss rational cancer surveillance strategies patients evidence limited suggest pragmatic approach regard recommend interval screening cca noninvasive imaging modalities serum carbohydrate antigen 19 9 determinations annually imaging studies also serve screen gallbladder cancer hcc screening colorectal cancer firmly established psc patients ibd includes colonoscopy time psc diagnosis thereafter 1 2 year intervals also highlight areas information required management biliary tract dysplasia cancer chemoprevention psc pubmed","probabilities":0.9799733,"Title":"Cancer surveillance in patients with primary sclerosing cholangitis","Abstract":"Primary sclerosing cholangitis (PSC) is a chronic fibroinflammatory syndrome involving the biliary tract, often accompanied by inflammatory bowel disease (IBD). This syndrome is a prototype disease linking chronic inflammation to carcinogenesis. Indeed, PSC is associated with an increased risk of cholangiocarcinoma (CCA), gallbladder cancer, hepatocellular carcinoma (HCC), and colorectal cancer. Herein, we review the risk for these malignancies in PSC and discuss rational cancer surveillance strategies for these patients. Where evidence is limited, we suggest a pragmatic approach. In this regard, we recommend interval screening for CCA with noninvasive imaging modalities and serum carbohydrate antigen 19-9 determinations annually. These imaging studies also serve to screen for gallbladder cancer and HCC. Screening for colorectal cancer is more firmly established in PSC patients with IBD and includes colonoscopy at the time of PSC diagnosis and, thereafter, at 1-2-year intervals. We also highlight areas where more information is required, such as management of biliary tract dysplasia and cancer chemoprevention in PSC.","Source":"PubMed","category":"HUMAN","training_data":"Cancer surveillance in patients with primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is a chronic fibroinflammatory syndrome involving the biliary tract, often accompanied by inflammatory bowel disease (IBD). This syndrome is a prototype disease linking chronic inflammation to carcinogenesis. Indeed, PSC is associated with an increased risk of cholangiocarcinoma (CCA), gallbladder cancer, hepatocellular carcinoma (HCC), and colorectal cancer. Herein, we review the risk for these malignancies in PSC and discuss rational cancer surveillance strategies for these patients. Where evidence is limited, we suggest a pragmatic approach. In this regard, we recommend interval screening for CCA with noninvasive imaging modalities and serum carbohydrate antigen 19-9 determinations annually. These imaging studies also serve to screen for gallbladder cancer and HCC. Screening for colorectal cancer is more firmly established in PSC patients with IBD and includes colonoscopy at the time of PSC diagnosis and, thereafter, at 1-2-year intervals. We also highlight areas where more information is required, such as management of biliary tract dysplasia and cancer chemoprevention in PSC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"therapeutic relevance targeted sequencing management patients advanced biliary tract cancer dna damage repair gene mutations predictive biomarker purpose biliary tract cancer btc standard chemotherapy limited benefit molecular targeted agents approved study investigated genetic profile btc identify potential new therapeutic targets predictive biomarkers methods targeted exome sequencing performed 124 patients btc gallbladder cancer gbc 25 intrahepatic cholangiocarcinoma icc 55 extrahepatic cholangiocarcinoma ecc 44 survival analysis performed 112 patients received palliative chemotherapy locally unresectable metastatic disease results genetic alterations observed 104 patients 83 8 commonly mutated genes tp53 44 4 kras 29 0 arid1a 12 1 idh1 9 7 idh1 2 mutations appeared frequently icc 23 6 p 0 0002 gbc 4 0 ecc 2 3 erbb2 3 mutations found gbc 20 0 ecc 11 4 patients harbouring tp53 mutations shorter overall survival os median 15 2 vs 37 8 months p 0 018 idh1 mutations showed tendency longer progression free survival pfs 10 6 vs 6 1 months p 0 124 potentially actionable genetic alterations found 54 8 7 1 received appropriate molecular targeted therapy clinical trial setting germline somatic mutations dna damage repair ddr genes found 63 5 patients significantly associated longer pfs 6 9 vs 5 7 months p 0 013 os 21 0 vs 13 3 months p 0 009 patients received first line platinum containing chemotherapies n 88 conclusions subgroup patients btc may benefit targeted therapy aid genetic information particular ddr alterations may predictive biomarker response platinum containing chemotherapy patients btc stn","probabilities":0.9799733,"Title":"Therapeutic Relevance Of Targeted Sequencing In Management Of Patients With Advanced Biliary Tract Cancer: Dna Damage Repair Gene Mutations As A Predictive Biomarker","Abstract":"Purpose: In biliary tract cancer (BTC), standard chemotherapy has limited benefit and no molecular targeted agents have been approved. This study investigated the genetic profile of BTC to identify potential new therapeutic targets and predictive biomarkers. \r\n\r\n Methods: Targeted exome sequencing was performed for 124 patients with BTC [gallbladder cancer (GBC), 25; intrahepatic cholangiocarcinoma (ICC), 55; extrahepatic cholangiocarcinoma (ECC), 44]. Survival analysis was performed in 112 patients who received palliative chemotherapy for locally unresectable or metastatic disease. \r\n\r\n Results: Genetic alterations were observed in 104 patients (83.8%); the most commonly mutated genes were TP53 (44.4%), KRAS (29.0%), ARID1A (12.1%) and IDH1 (9.7%). IDH1/2 mutations appeared more frequently in ICC (23.6%, P = 0.0002) than in GBC (4.0%) or ECC (2.3%), while ERBB2/3 mutations were found only in GBC (20.0%) and ECC (11.4%). Patients harbouring TP53 mutations had shorter overall survival (OS; median 15.2 vs. 37.8 months, P = 0.018), while IDH1 mutations showed a tendency for longer progression-free survival (PFS; 10.6 vs. 6.1 months, P = 0.124). Potentially actionable genetic alterations were found in 54.8%, and 7.1% received appropriate molecular targeted therapy in the clinical trial setting. Germline or somatic mutations in DNA damage repair (DDR) genes were found in 63.5% of patients and were significantly associated with longer PFS (6.9 vs. 5.7 months, P = 0.013) and OS (21.0 vs. 13.3 months, P = 0.009) in patients who received first-line platinum-containing chemotherapies (n = 88). \r\n\r\n Conclusions: A subgroup of patients with BTC may benefit from targeted therapy by the aid of genetic information. In particular, DDR alterations may be a predictive biomarker for response to platinum-containing chemotherapy in patients with BTC.","Source":"STN","category":"HUMAN","training_data":"Therapeutic Relevance Of Targeted Sequencing In Management Of Patients With Advanced Biliary Tract Cancer: Dna Damage Repair Gene Mutations As A Predictive Biomarker Purpose: In biliary tract cancer (BTC), standard chemotherapy has limited benefit and no molecular targeted agents have been approved. This study investigated the genetic profile of BTC to identify potential new therapeutic targets and predictive biomarkers. \r\n\r\n Methods: Targeted exome sequencing was performed for 124 patients with BTC [gallbladder cancer (GBC), 25; intrahepatic cholangiocarcinoma (ICC), 55; extrahepatic cholangiocarcinoma (ECC), 44]. Survival analysis was performed in 112 patients who received palliative chemotherapy for locally unresectable or metastatic disease. \r\n\r\n Results: Genetic alterations were observed in 104 patients (83.8%); the most commonly mutated genes were TP53 (44.4%), KRAS (29.0%), ARID1A (12.1%) and IDH1 (9.7%). IDH1/2 mutations appeared more frequently in ICC (23.6%, P = 0.0002) than in GBC (4.0%) or ECC (2.3%), while ERBB2/3 mutations were found only in GBC (20.0%) and ECC (11.4%). Patients harbouring TP53 mutations had shorter overall survival (OS; median 15.2 vs. 37.8 months, P = 0.018), while IDH1 mutations showed a tendency for longer progression-free survival (PFS; 10.6 vs. 6.1 months, P = 0.124). Potentially actionable genetic alterations were found in 54.8%, and 7.1% received appropriate molecular targeted therapy in the clinical trial setting. Germline or somatic mutations in DNA damage repair (DDR) genes were found in 63.5% of patients and were significantly associated with longer PFS (6.9 vs. 5.7 months, P = 0.013) and OS (21.0 vs. 13.3 months, P = 0.009) in patients who received first-line platinum-containing chemotherapies (n = 88). \r\n\r\n Conclusions: A subgroup of patients with BTC may benefit from targeted therapy by the aid of genetic information. In particular, DDR alterations may be a predictive biomarker for response to platinum-containing chemotherapy in patients with BTC. STN","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer epidemiology genetic risk associations gallbladder cancer gbc form hepatobiliary malignancy develops mucosal lining gallbladder early development gallbladder cancer usually asymptomatic gallbladder cancer high propensity metastatic dissemination thus patients diagnosed intermediate advanced stages curative treatment consequently gallbladder cancer highly lethal though overall global incidence gallbladder cancer low marked geographic variation ethnic communities asia well native american populations north south america affected disproportionately article provides comprehensive overview current epidemiology risk protective factors associated gallbladder cancer development addition current knowledge environmental genetic risk associations gallbladder cancer need additional large scale genome wide association studies gwas discussed pubmed","probabilities":0.9799733,"Title":"Gallbladder cancer: epidemiology and genetic risk associations","Abstract":"Gallbladder cancer (GBC) is a form of hepatobiliary malignancy that develops from the mucosal lining of the gallbladder. The early development of gallbladder cancer is usually asymptomatic and gallbladder cancer has a high propensity to metastatic dissemination, thus most patients are diagnosed at intermediate to advanced stages for which there is no curative treatment. Consequently, gallbladder cancer is highly lethal. Though the overall global incidence of gallbladder cancer is low, there is marked geographic variation and ethnic communities in Asia as well as Native American populations in both North and South America are affected disproportionately. This article provides a comprehensive overview of the current epidemiology and risk and protective factors associated with gallbladder cancer development. In addition, the current knowledge on environmental and genetic risk associations for gallbladder cancer and the need for additional large-scale genome wide association studies (GWAS) are discussed.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder cancer: epidemiology and genetic risk associations Gallbladder cancer (GBC) is a form of hepatobiliary malignancy that develops from the mucosal lining of the gallbladder. The early development of gallbladder cancer is usually asymptomatic and gallbladder cancer has a high propensity to metastatic dissemination, thus most patients are diagnosed at intermediate to advanced stages for which there is no curative treatment. Consequently, gallbladder cancer is highly lethal. Though the overall global incidence of gallbladder cancer is low, there is marked geographic variation and ethnic communities in Asia as well as Native American populations in both North and South America are affected disproportionately. This article provides a comprehensive overview of the current epidemiology and risk and protective factors associated with gallbladder cancer development. In addition, the current knowledge on environmental and genetic risk associations for gallbladder cancer and the need for additional large-scale genome wide association studies (GWAS) are discussed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"human equilibrative nucleoside transporter 1 hent1 levels predict response gemcitabine patients biliary tract cancer btc background aim translational data suggest nucleoside transporters particular human equilibrative nucleoside transporter 1 hent1 play important role predicting clinical outcome gemcitabine chemotherapy several types cancer aim study retrospectively determine patients outcome according expression hent1 tumoral cells patients receiving gemcitabine based therapy materials methods immunohistochemistry analysis performed samples thirty one patients unresectable biliary tract cancer btc consecutively treated first line gemcitabine based regimens results positive hent1 staining patients 21 67 7 negative hent1 staining patients 10 32 3 statistical analysis revealed association baseline characteristics toxicities tumor response gemcitabine hent1 levels univariate analysis hent1 expression significantly correlated time progression ttp p 0 0394 hr 2 902 95 ci 1 053 7 996 median ttp 6 33 versus 2 83 months respectively patients positive versus negative hent1 staining moreover patients positive hent1 expression showed longer median overall survival compared patients low hent1 expression 14 versus 7 months respectively difference reach statistical significance p 0 128 conclusions therefore hent1 may relevant predictive marker benefit gemcitabine based therapies patients advanced btc pubmed","probabilities":0.8684211,"Title":"Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC)","Abstract":"BACKGROUND AND AIM: Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy. MATERIALS AND METHODS: The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens. RESULTS: Positive hENT1 staining patients were 21 (67.7%); negative hENT1 staining patients were 10 (32.3%). Statistical analysis revealed no association between baseline characteristics, toxicities and tumor response to gemcitabine and hENT1 levels. In the univariate analysis, HENT1 expression was significantly correlated with time to progression (TTP) (p=0.0394; HR 2.902, 95%CI 1.053-7.996). The median TTP was 6.33 versus 2.83 months, respectively in patients with positive versus negative hENT1 staining. Moreover, patients with positive hENT1 expression showed a longer median overall survival when compared with patients with low hENT1 expression (14 versus 7 months, respectively), but this difference did not reach the statistical significance (p=0.128). CONCLUSIONS: Therefore, hENT1 may be a relevant predictive marker of benefit from gemcitabine-based therapies in patients with advanced BTC.","Source":"PubMed","category":"HUMAN","training_data":"Human equilibrative nucleoside transporter 1 (hENT1) levels predict response to gemcitabine in patients with biliary tract cancer (BTC) BACKGROUND AND AIM: Translational data suggest that nucleoside transporters, in particular human equilibrative nucleoside transporter 1 (hENT1), play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of this study was to retrospectively determine patients' outcome according to the expression of hENT1 in tumoral cells of patients receiving gemcitabine-based therapy. MATERIALS AND METHODS: The immunohistochemistry analysis was performed on samples from thirty-one patients with unresectable biliary tract cancer (BTC) consecutively treated with first line gemcitabine-based regimens. RESULTS: Positive hENT1 staining patients were 21 (67.7%); negative hENT1 staining patients were 10 (32.3%). Statistical analysis revealed no association between baseline characteristics, toxicities and tumor response to gemcitabine and hENT1 levels. In the univariate analysis, HENT1 expression was significantly correlated with time to progression (TTP) (p=0.0394; HR 2.902, 95%CI 1.053-7.996). The median TTP was 6.33 versus 2.83 months, respectively in patients with positive versus negative hENT1 staining. Moreover, patients with positive hENT1 expression showed a longer median overall survival when compared with patients with low hENT1 expression (14 versus 7 months, respectively), but this difference did not reach the statistical significance (p=0.128). CONCLUSIONS: Therefore, hENT1 may be a relevant predictive marker of benefit from gemcitabine-based therapies in patients with advanced BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"oncologic effects preoperative biliary drainage resectable hilar cholangiocarcinoma percutaneous biliary drainage adverse effects survival background objectives objective current study define long term survival patients resectable hilar cholangiocarcinoma hcca preoperative percutaneous transhepatic biliary drainage ptbd versus endoscopic biliary drainage ebd methods 2000 2014 240 patients underwent curative intent resection hcca identified 10 major hepatobiliary centers postoperative morbidity mortality well disease specific survival dss recurrence free survival rfs analyzed among patients results median decrease total bilirubin levels biliary drainage similar comparing ptbd n 104 versus ebd n 92 mg dl 4 9 vs 4 9 p 0 589 surgery difference baseline demographic characteristics type surgical procedure performed final ajcc tumor stage postoperative morbidity among patients underwent ebd versus ptbd p 0 05 patients underwent ptbd versus ebd comparable long term dss median 43 7 vs 36 9 months p 0 802 rfs median 26 7 vs 24 0 months p 0 571 overall pattern recurrence relative regional distant disease also among patients undergoing ptbd ebd p 0 669 conclusions oncologic outcomes including dss rfs similar among patients underwent ptbd versus ebd difference tumor recurrence location pubmed","probabilities":0.9799733,"Title":"Oncologic effects of preoperative biliary drainage in resectable hilar cholangiocarcinoma: Percutaneous biliary drainage has no adverse effects on survival","Abstract":"BACKGROUND AND OBJECTIVES: The objective of the current study was to define long-term survival of patients with resectable hilar cholangiocarcinoma (HCCA) after preoperative percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD). METHODS: Between 2000 and 2014, 240 patients who underwent curative-intent resection for HCCA were identified at 10 major hepatobiliary centers. Postoperative morbidity and mortality, as well as disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed among patients. RESULTS: The median decrease in total bilirubin levels after biliary drainage was similar comparing PTBD (n = 104) versus EBD (n = 92) (mg/dL, 4.9 vs 4.9, P = 0.589) before surgery. There was no difference in baseline demographic characteristics, type of surgical procedure performed, final AJCC tumor stage or postoperative morbidity among patients who underwent EBD only versus PTBD (all P > 0.05). Patients who underwent PTBD versus EBD had a comparable long-term DSS (median, 43.7 vs 36.9 months, P = 0.802) and RFS (median, 26.7 vs 24.0 months, P = 0.571). The overall pattern of recurrence relative to regional or distant disease was also the same among patients undergoing PTBD and EBD (P = 0.669) CONCLUSIONS: Oncologic outcomes including DSS and RFS were similar among patients who underwent PTBD versus EBD with no difference in tumor recurrence location.","Source":"PubMed","category":"HUMAN","training_data":"Oncologic effects of preoperative biliary drainage in resectable hilar cholangiocarcinoma: Percutaneous biliary drainage has no adverse effects on survival BACKGROUND AND OBJECTIVES: The objective of the current study was to define long-term survival of patients with resectable hilar cholangiocarcinoma (HCCA) after preoperative percutaneous transhepatic biliary drainage (PTBD) versus endoscopic biliary drainage (EBD). METHODS: Between 2000 and 2014, 240 patients who underwent curative-intent resection for HCCA were identified at 10 major hepatobiliary centers. Postoperative morbidity and mortality, as well as disease-specific survival (DSS) and recurrence-free survival (RFS) were analyzed among patients. RESULTS: The median decrease in total bilirubin levels after biliary drainage was similar comparing PTBD (n = 104) versus EBD (n = 92) (mg/dL, 4.9 vs 4.9, P = 0.589) before surgery. There was no difference in baseline demographic characteristics, type of surgical procedure performed, final AJCC tumor stage or postoperative morbidity among patients who underwent EBD only versus PTBD (all P > 0.05). Patients who underwent PTBD versus EBD had a comparable long-term DSS (median, 43.7 vs 36.9 months, P = 0.802) and RFS (median, 26.7 vs 24.0 months, P = 0.571). The overall pattern of recurrence relative to regional or distant disease was also the same among patients undergoing PTBD and EBD (P = 0.669) CONCLUSIONS: Oncologic outcomes including DSS and RFS were similar among patients who underwent PTBD versus EBD with no difference in tumor recurrence location. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intra hepatic cholangiocarcinoma frequency demographic patterns thirty year data md anderson cancer center purpose recent reports shown increase frequency intra hepatic cholangiocarcinoma ihc stable decreased frequency extra hepatic cholangiocarcinoma ehc however data demographic patterns associated change limited analyzed cases cholangiocarcinoma cc aim study frequency demographic patterns time ihc ehc methods data collected md anderson cancer center tumor registry cc 1978 2007 stratified age 50 50 59 60 69 70 years gender ethnicity caucasian african american hispanic time 1978 1987 1988 1997 1998 2007 diagnosis ihc ehc chi square tests logistic regression used statistics results 1 061 cc 445 ihc proportion ihc increased 30 1978 1998 48 1998 2007 p 0 0001 compared ehc ihc occurred frequently relatively young age 60 years 21 27 vs 15 23 0 49 years 50 59 years respectively p 0 003 females 48 vs 42 p 0 03 ethnic distribution similar significant p 0 019 interaction age gender using logistic regression analysis conclusions increase frequency ihc occurred time frequently observed among females 60 years data may implications understanding pathogenesis ihc stn","probabilities":0.9799733,"Title":"Intra-Hepatic Cholangiocarcinoma--Frequency And Demographic Patterns: Thirty-Year Data From The Md Anderson Cancer Center","Abstract":"Purpose: Recent reports have shown an increase in frequency of intra-hepatic cholangiocarcinoma (IHC) with a stable or decreased frequency of extra-hepatic cholangiocarcinoma (EHC). However, data on the demographic patterns associated with this change are limited. We analyzed cases of cholangiocarcinoma (CC) with aim to study frequency and demographic patterns over time of IHC and EHC. \n\n Methods: Data were collected from MD Anderson Cancer Center Tumor Registry on CC (1978-2007) and stratified on age (<50, 50-59, 60-69, and ≥70 years), gender, ethnicity (Caucasian, African-American, Hispanic, and Other), time (1978-1987, 1988-1997, 1998-2007), and diagnosis (IHC and EHC). Chi-square tests and logistic regression were used for statistics. \n\n Results: Of 1,061 CC (445 IHC), proportion of IHC increased from 30% in 1978-1998 to 48% during 1998-2007 (P < 0.0001). Compared to EHC, IHC occurred more frequently in relatively young (age < 60 years) (21 and 27% vs. 15 and 23% in 0-49 years and 50-59 years, respectively; P = 0.003) and females (48 vs. 42%, P = 0.03). Ethnic distribution was similar. There was significant (P = 0.019) interaction between age and gender using logistic regression analysis. \n\n Conclusions: Increase in frequency of IHC occurred over time and is more frequently observed among females <60 years. These data may have implications in understanding pathogenesis of IHC.","Source":"STN","category":"HUMAN","training_data":"Intra-Hepatic Cholangiocarcinoma--Frequency And Demographic Patterns: Thirty-Year Data From The Md Anderson Cancer Center Purpose: Recent reports have shown an increase in frequency of intra-hepatic cholangiocarcinoma (IHC) with a stable or decreased frequency of extra-hepatic cholangiocarcinoma (EHC). However, data on the demographic patterns associated with this change are limited. We analyzed cases of cholangiocarcinoma (CC) with aim to study frequency and demographic patterns over time of IHC and EHC. \n\n Methods: Data were collected from MD Anderson Cancer Center Tumor Registry on CC (1978-2007) and stratified on age (<50, 50-59, 60-69, and ≥70 years), gender, ethnicity (Caucasian, African-American, Hispanic, and Other), time (1978-1987, 1988-1997, 1998-2007), and diagnosis (IHC and EHC). Chi-square tests and logistic regression were used for statistics. \n\n Results: Of 1,061 CC (445 IHC), proportion of IHC increased from 30% in 1978-1998 to 48% during 1998-2007 (P < 0.0001). Compared to EHC, IHC occurred more frequently in relatively young (age < 60 years) (21 and 27% vs. 15 and 23% in 0-49 years and 50-59 years, respectively; P = 0.003) and females (48 vs. 42%, P = 0.03). Ethnic distribution was similar. There was significant (P = 0.019) interaction between age and gender using logistic regression analysis. \n\n Conclusions: Increase in frequency of IHC occurred over time and is more frequently observed among females <60 years. These data may have implications in understanding pathogenesis of IHC. STN","prediction_labels":"HUMAN"},{"cleaned":"predictors incidental gallbladder cancer patients undergoing cholecystectomy benign gallbladder disease results population based gallstone surgery registry background gallbladder cancer rare neoplasm poor prognosis early diagnosis correct treatment strategy important aim study identify predictors incidental gallbladder cancer methods data cholecystectomies registered nationwide swedish register gallstone surgery 2007 2014 analyzed incidental gallbladder cancer exclusion criteria patients gallbladder sent histopathology preoperative suspicion polyps gallbladder cancer indication operation reasons gallstone disease predictive factors incidental gallbladder cancer identified using multivariable logistic regression results total 86 154 procedures registered swedish register gallstone surgery 36 355 patients included analysis 215 included patients incidental gallbladder cancer 0 59 mean age 70 11 years index cases 54 16 years control group 80 cases 60 controls female predictors incidental gallbladder cancer older age odds ratio 1 08 p 001 female sex odds ratio 3 58 p 001 previous cholecystitis odds ratio 1 37 p 045 combination acute cholecystitis without jaundice odds ratio 1 39 p 041 jaundice without acute cholecystitis odds ratio 2 02 p 009 preoperative risk model including factors gave area receiver operating characteristic curve 0 82 adding macroscopic evaluation gallbladder surgeon area receiver operating characteristic curve increased 0 87 intraoperatively suspected gallbladder cancer confirmed cancer 31 cases conclusion incidental gallbladder cancer likely diagnosed older patients women previous cholecystitis jaundice acute cholecystitis also shown important risk factors intraoperative inspection gallbladder improved risk model stn","probabilities":0.9799733,"Title":"Predictors Of Incidental Gallbladder Cancer In Patients Undergoing Cholecystectomy For Benign Gallbladder Disease: Results From A Population-Based Gallstone Surgery Registry","Abstract":"Background: Gallbladder cancer is a rare neoplasm with a poor prognosis. Early diagnosis and correct treatment strategy is important. The aim of this study was to identify predictors for incidental gallbladder cancer. \r\n\r\n Methods: Data from cholecystectomies registered in the nationwide Swedish Register for Gallstone Surgery between 2007 and 2014 were analyzed for incidental gallbladder cancer. Exclusion criteria were patients with a gallbladder not sent for histopathology, preoperative suspicion of polyps/gallbladder cancer, and indication for operation for other reasons than gallstone disease. Predictive factors for incidental gallbladder cancer were identified using multivariable logistic regression. \r\n\r\n Results: A total of 86,154 procedures were registered in the Swedish Register for Gallstone Surgery. Of these, 36,355 patients were included in the analysis, and 215 of the included patients had incidental gallbladder cancer (0.59%). Mean age was 70 ± 11 years for index cases and 54 ± 16 years for the control group, and 80% of cases and 60% of controls were female. Predictors for incidental gallbladder cancer were older age (odds ratio = 1.08; P < .001), female sex (odds ratio = 3.58; P < .001), previous cholecystitis (odds ratio = 1.37; P = .045), and the combination of acute cholecystitis without jaundice (odds ratio = 1.39; P = .041) and jaundice without acute cholecystitis (odds ratio = 2.02; P = .009). A preoperative risk model including these factors gave an area under receiver operating characteristic curve of 0.82. By adding macroscopic evaluation of the gallbladder by the surgeon, the area under receiver operating characteristic curve increased to 0.87. Intraoperatively suspected gallbladder cancer was confirmed as cancer in 31% of the cases. \r\n\r\n Conclusion: Incidental gallbladder cancer is more likely to be diagnosed in older patients, women, and after previous cholecystitis. Jaundice and acute cholecystitis were also shown to be important risk factors. Intraoperative inspection of the gallbladder improved the risk model.","Source":"STN","category":"HUMAN","training_data":"Predictors Of Incidental Gallbladder Cancer In Patients Undergoing Cholecystectomy For Benign Gallbladder Disease: Results From A Population-Based Gallstone Surgery Registry Background: Gallbladder cancer is a rare neoplasm with a poor prognosis. Early diagnosis and correct treatment strategy is important. The aim of this study was to identify predictors for incidental gallbladder cancer. \r\n\r\n Methods: Data from cholecystectomies registered in the nationwide Swedish Register for Gallstone Surgery between 2007 and 2014 were analyzed for incidental gallbladder cancer. Exclusion criteria were patients with a gallbladder not sent for histopathology, preoperative suspicion of polyps/gallbladder cancer, and indication for operation for other reasons than gallstone disease. Predictive factors for incidental gallbladder cancer were identified using multivariable logistic regression. \r\n\r\n Results: A total of 86,154 procedures were registered in the Swedish Register for Gallstone Surgery. Of these, 36,355 patients were included in the analysis, and 215 of the included patients had incidental gallbladder cancer (0.59%). Mean age was 70 ± 11 years for index cases and 54 ± 16 years for the control group, and 80% of cases and 60% of controls were female. Predictors for incidental gallbladder cancer were older age (odds ratio = 1.08; P < .001), female sex (odds ratio = 3.58; P < .001), previous cholecystitis (odds ratio = 1.37; P = .045), and the combination of acute cholecystitis without jaundice (odds ratio = 1.39; P = .041) and jaundice without acute cholecystitis (odds ratio = 2.02; P = .009). A preoperative risk model including these factors gave an area under receiver operating characteristic curve of 0.82. By adding macroscopic evaluation of the gallbladder by the surgeon, the area under receiver operating characteristic curve increased to 0.87. Intraoperatively suspected gallbladder cancer was confirmed as cancer in 31% of the cases. \r\n\r\n Conclusion: Incidental gallbladder cancer is more likely to be diagnosed in older patients, women, and after previous cholecystitis. Jaundice and acute cholecystitis were also shown to be important risk factors. Intraoperative inspection of the gallbladder improved the risk model. STN","prediction_labels":"HUMAN"},{"cleaned":"tumor location strong predictor tumor progression survival t2 gallbladder cancer international multicenter study objective determine prognostic impact tumor location gallbladder cancer background depth tumor strong predictor survival curative resection gallbladder cancer however gallbladder unique anatomical relationship liver clinical significance tumor location remains unclear methods 437 patients gallbladder cancer underwent resection 4 international institutions clinicopathologic characteristics association survival analyzed tumor location defined hepatic side peritoneal side prognostic significance tumor location evaluated results among 252 patients t2 disease patients tumors hepatic side t2h n 99 higher rates vascular invasion neural invasion nodal metastasis patients tumors peritoneal side t2p n 153 51 vs 19 33 vs 8 40 vs 17 respectively p 0 01 median follow 58 9 months 3 year 5 year survival rates 52 1 42 6 respectively t2h tumors 73 7 64 7 respectively t2p tumors p 0 0006 differences observed t1 t3 tumors multivariate analysis confirmed independent association hepatic side location survival t2 tumors hazard ratio 2 7 95 confidence interval 1 7 4 2 p 0 001 subclassification t2 tumors predicted recurrence liver 23 vs 3 p 0 003 distant lymph nodes 16 vs 3 p 0 019 even radical resection conclusions curative resection t2 gallbladder cancer tumor location predicts pattern recurrence survival pubmed","probabilities":0.9799733,"Title":"Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study","Abstract":"OBJECTIVE: To determine the prognostic impact of tumor location in gallbladder cancer. BACKGROUND: Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear. METHODS: For 437 patients with gallbladder cancer who underwent resection at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as \"hepatic side\" or \"peritoneal side,\" and the prognostic significance of tumor location was evaluated. RESULTS: Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs 8%, and 40% vs 17%, respectively; P < 0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P < 0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P = 0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical resection. CONCLUSIONS: After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival.","Source":"PubMed","category":"HUMAN","training_data":"Tumor location is a strong predictor of tumor progression and survival in T2 gallbladder cancer: an international multicenter study OBJECTIVE: To determine the prognostic impact of tumor location in gallbladder cancer. BACKGROUND: Depth of tumor is a strong predictor of survival after curative resection of gallbladder cancer. However, the gallbladder has a unique anatomical relationship with the liver, and the clinical significance of tumor location remains unclear. METHODS: For 437 patients with gallbladder cancer who underwent resection at 4 international institutions, clinicopathologic characteristics and their association with survival were analyzed. Tumor location was defined as \"hepatic side\" or \"peritoneal side,\" and the prognostic significance of tumor location was evaluated. RESULTS: Among the 252 patients with T2 disease, patients with tumors on the hepatic side (T2h, n = 99) had higher rates of vascular invasion, neural invasion, and nodal metastasis than patients with tumors on the peritoneal side (T2p, n = 153) (51% vs 19%, 33% vs 8%, and 40% vs 17%, respectively; P < 0.01 for all). After a median follow-up of 58.9 months, 3-year and 5-year survival rates were 52.1% and 42.6%, respectively, for T2h tumors and 73.7% and 64.7%, respectively, for T2p tumors (P = 0.0006). No such differences were observed in T1 or T3 tumors. Multivariate analysis confirmed the independent association of hepatic-side location with survival in T2 tumors (hazard ratio, 2.7; 95% confidence interval, 1.7-4.2; P < 0.001). This subclassification of T2 tumors predicted recurrence in the liver (23% vs 3%; P = 0.003) and distant lymph nodes (16% vs 3%; P = 0.019) even after radical resection. CONCLUSIONS: After curative resection of T2 gallbladder cancer, tumor location predicts the pattern of recurrence and survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ablative therapy unresectable intrahepatic cholangiocarcinoma systematic review meta analysis background intrahepatic cholangiocarcinoma icca usually fatal malignancy rising incidence globally surgical resection currently remains curative treatment however minority icca amenable resection new therapeutic modalities needed aims systematically review perform meta analysis existing literature regarding use ablative therapies icca assess efficacy treatment modality calculating pooled survival results investigate associations prognostic factors survival methods comprehensive search pubmed database relevant articles performed studies assessing survival patients icca undergoing ablation included data extracted patient tumour treatment characteristics survival random effects meta analysis used pool data galbraith plots used investigate heterogeneity bubble plots formulated using regression based meta analysis results total 10 studies included final analysis yielding aggregate 206 patients 69 5 males median age 51 2 72 5 320 tumours patients 70 4 recurrent cases icca 29 6 cases primary icca median overall survival ranged 8 7 52 4 months pooled 1 3 5 year survival rates 76 95 confidence interval 68 83 33 21 44 16 7 26 respectively significant association found median age number tumours median tumour size 1 year survival conclusions ablative therapies display promising potential treatment modalities icca however research necessary validate findings stn","probabilities":0.9799733,"Title":"Ablative Therapy For Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review And Meta-Analysis","Abstract":"Background: Intrahepatic cholangiocarcinoma (iCCA) is usually a fatal malignancy with rising incidence globally. Surgical resection currently remains the only curative treatment. However, as only a minority of iCCA is amenable to resection, new therapeutic modalities are needed. Our aims were to systematically review and perform a meta-analysis on the existing literature regarding the use of ablative therapies for iCCA and to assess their efficacy as a treatment modality by calculating pooled survival results and investigate associations between prognostic factors and survival. \r\n\r\n Methods: A comprehensive search of the PubMed database for relevant articles was performed. Studies assessing survival in patients with iCCA undergoing ablation were included. Data were extracted on patient, tumour and treatment characteristics and survival. Random effects meta-analysis was used to pool the data. Galbraith plots were used to investigate heterogeneity; bubble plots were formulated using regression-based meta-analysis. \r\n\r\n Results: A total of 10 studies were included in the final analysis, yielding an aggregate of 206 patients (69.5% males, median age: 51.2-72.5) and 320 tumours. Of all patients, 70.4% were recurrent cases of iCCA, and 29.6% were cases of primary iCCA. The median overall survival ranged from 8.7 to 52.4 months. Pooled 1-, 3- and 5-year survival rates were 76% (95% confidence interval: 68-83%), 33% (21-44%) and 16% (7-26%), respectively. No significant association was found between the median age, number of tumours or median tumour size and 1-year survival. \r\n\r\n Conclusions: Ablative therapies display promising potential as treatment modalities for iCCA. However, further research is necessary to validate these findings.","Source":"STN","category":"HUMAN","training_data":"Ablative Therapy For Unresectable Intrahepatic Cholangiocarcinoma: A Systematic Review And Meta-Analysis Background: Intrahepatic cholangiocarcinoma (iCCA) is usually a fatal malignancy with rising incidence globally. Surgical resection currently remains the only curative treatment. However, as only a minority of iCCA is amenable to resection, new therapeutic modalities are needed. Our aims were to systematically review and perform a meta-analysis on the existing literature regarding the use of ablative therapies for iCCA and to assess their efficacy as a treatment modality by calculating pooled survival results and investigate associations between prognostic factors and survival. \r\n\r\n Methods: A comprehensive search of the PubMed database for relevant articles was performed. Studies assessing survival in patients with iCCA undergoing ablation were included. Data were extracted on patient, tumour and treatment characteristics and survival. Random effects meta-analysis was used to pool the data. Galbraith plots were used to investigate heterogeneity; bubble plots were formulated using regression-based meta-analysis. \r\n\r\n Results: A total of 10 studies were included in the final analysis, yielding an aggregate of 206 patients (69.5% males, median age: 51.2-72.5) and 320 tumours. Of all patients, 70.4% were recurrent cases of iCCA, and 29.6% were cases of primary iCCA. The median overall survival ranged from 8.7 to 52.4 months. Pooled 1-, 3- and 5-year survival rates were 76% (95% confidence interval: 68-83%), 33% (21-44%) and 16% (7-26%), respectively. No significant association was found between the median age, number of tumours or median tumour size and 1-year survival. \r\n\r\n Conclusions: Ablative therapies display promising potential as treatment modalities for iCCA. However, further research is necessary to validate these findings. STN","prediction_labels":"HUMAN"},{"cleaned":"conjugated bile acids promote cholangiocarcinoma cell invasive growth activation sphingosine 1 phosphate receptor 2 cholangiocarcinoma cca often fatal primarymalignancyof intra extrahepatic biliary tract commonly associated chronic cholestasis signi cantlyelevated levels primary conjugated bile acids cbas correlated bile duct obstruction bdo bdo also recently shown promote cca progression however whereas increasing evidence linking chronic cholestasis abnormal bile acid pro les cca development progression speci c mechanisms bile acids may acting promote cholangiocarcinogenesis invasive biliary tumor growth fully established recent studies shown cbas free bile acids stimulate cca cell growth imbalance ratio free cbas may play important role tumorigenesis cca also cbas able activate extracellular signal regulated kinase erk 1 2 phosphatidylinositol 3 kinase protein kinase b akt signaling pathways sphingosine 1 phosphate receptor 2 s1pr2 rodent hepatocytes current study demonstrate s1pr2 highly expressed rat human cca cells well human cca tissues show cbas activate erk1 2 akt signaling pathways signi cantly stimulate cca cell growth invasion vitro taurocholate tca mediated cca cell proliferation migration invasion signi cantly inhibited jte 013 chemical antagonist s1pr2 lentiviral short hairpin rna silencing s1pr2 novel organotypic rat cca coculture model tca found signi cantly increase growth cca cell spheroidal duct like structures blocked treatment jte 013 conclusion collective data support hypothesis cbas promote cca cell invasive growth s1pr2 google scholar","probabilities":0.9467213,"Title":"Conjugated Bile Acids Promote Cholangiocarcinoma Cell Invasive Growth Through Activation Of Sphingosine 1-Phosphate Receptor 2","Abstract":"Cholangiocarcinoma (CCA) is an often fatal primarymalignancyof the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantlyelevated levels of primary and conjugated bile acids (CBAs), which are correlated with bile duct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, the specific mechanisms by which bile acids may be acting to promote cholangiocarcinogenesis and invasive biliary tumor growth have not been fully established. Recent studies have shown that CBAs, but not free bile acids, stimulate CCA cell growth, and that an imbalance in the ratio of free to CBAs may play an important role in the tumorigenesis of CCA. Also, CBAs are able to activate extracellular signal-regulated kinase (ERK)1/2- and phosphatidylinositol-3-kinase/protein kinase B (AKT)-signaling pathways through sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes. In the current study, we demonstrate S1PR2 to be highly expressed in rat and human CCA cells, as well as in human CCA tissues. We further show that CBAs activate the ERK1/2- and AKT-signaling pathways and significantly stimulate CCA cell growth and invasion in vitro. Taurocholate (TCA)-mediated CCA cell proliferation, migration, and invasion were significantly inhibited by JTE-013, a chemical antagonist of S1PR2, or by lentiviral short hairpin RNA silencing of S1PR2. In a novel organotypic rat CCA coculture model, TCA was further found to significantly increase the growth of CCA cell spheroidal/“duct-like” structures, which was blocked by treatment with JTE-013. Conclusion: Our collective data support the hypothesis that CBAs promote CCA cell-invasive growth through S1PR2","Source":"Google Scholar","category":"ANIMAL","training_data":"Conjugated Bile Acids Promote Cholangiocarcinoma Cell Invasive Growth Through Activation Of Sphingosine 1-Phosphate Receptor 2 Cholangiocarcinoma (CCA) is an often fatal primarymalignancyof the intra- and extrahepatic biliary tract that is commonly associated with chronic cholestasis and significantlyelevated levels of primary and conjugated bile acids (CBAs), which are correlated with bile duct obstruction (BDO). BDO has also recently been shown to promote CCA progression. However, whereas there is increasing evidence linking chronic cholestasis and abnormal bile acid profiles to CCA development and progression, the specific mechanisms by which bile acids may be acting to promote cholangiocarcinogenesis and invasive biliary tumor growth have not been fully established. Recent studies have shown that CBAs, but not free bile acids, stimulate CCA cell growth, and that an imbalance in the ratio of free to CBAs may play an important role in the tumorigenesis of CCA. Also, CBAs are able to activate extracellular signal-regulated kinase (ERK)1/2- and phosphatidylinositol-3-kinase/protein kinase B (AKT)-signaling pathways through sphingosine 1-phosphate receptor 2 (S1PR2) in rodent hepatocytes. In the current study, we demonstrate S1PR2 to be highly expressed in rat and human CCA cells, as well as in human CCA tissues. We further show that CBAs activate the ERK1/2- and AKT-signaling pathways and significantly stimulate CCA cell growth and invasion in vitro. Taurocholate (TCA)-mediated CCA cell proliferation, migration, and invasion were significantly inhibited by JTE-013, a chemical antagonist of S1PR2, or by lentiviral short hairpin RNA silencing of S1PR2. In a novel organotypic rat CCA coculture model, TCA was further found to significantly increase the growth of CCA cell spheroidal/“duct-like” structures, which was blocked by treatment with JTE-013. Conclusion: Our collective data support the hypothesis that CBAs promote CCA cell-invasive growth through S1PR2 Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"appraisal inflammation based prognostic scores patients unresectable perihilar cholangiocarcinoma background inflammation based prognostic scores useful prognostic indicators several types cancer aim study evaluate whether scores predict survival impact unresectable perihilar cholangiocarcinoma methods modified glasgow prognostic score mgps neutrophil lymphocyte ratio nlr platelet lymphocyte ratio prognostic nutritional index retrospectively assessed 219 patients unresectable perihilar cholangiocarcinoma results four scores evaluated mgps nlr demonstrated prognostic value whereas remaining two systems median survival time mst patients mgps 0 nlr 0 1 significantly better patients mgps 1 2 nlr 2 12 3 vs 4 8 months p 0 001 10 5 vs 4 4 months p 0 001 multivariate analysis revealed mgps nlr independent prognostic factors combination mgps nlr stratified survival well mst 12 8 months patients mgps 0 nlr 1 2 3 0 months patients mgps 1 2 nlr 2 conclusions mgps nlr independent prognostic factors pivotal refining patient stratification unresectable perihilar cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Appraisal of inflammation-based prognostic scores in patients with unresectable perihilar cholangiocarcinoma","Abstract":"BACKGROUND: Inflammation-based prognostic scores are useful prognostic indicators for several types of cancer. The aim of this study was to evaluate whether the scores predict survival impact in unresectable perihilar cholangiocarcinoma. METHODS: The modified Glasgow Prognostic Score (mGPS), Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio, and Prognostic Nutritional Index, were retrospectively assessed in 219 patients with unresectable perihilar cholangiocarcinoma. RESULTS: Of the four scores evaluated, mGPS and NLR demonstrated prognostic value, whereas the remaining two systems did not. The median survival time (MST) of patients with a mGPS of 0 and NLR of 0 or 1 were significantly better than that of patients with a mGPS of 1 or 2 and NLR of 2 (12.3 vs. 4.8 months, P < 0.001, and 10.5 vs. 4.4 months, P = 0.001). Multivariate analysis revealed that both mGPS and NLR were independent prognostic factors. The combination of mGPS and NLR stratified survival well: the MST was 12.8 months in patients with a mGPS of 0 and NLR of 1 or 2, while only 3.0 months in patients with a mGPS of 1 or 2 and NLR of 2. CONCLUSIONS: Both mGPS and NLR are independent prognostic factors and pivotal in refining patient stratification in unresectable perihilar cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Appraisal of inflammation-based prognostic scores in patients with unresectable perihilar cholangiocarcinoma BACKGROUND: Inflammation-based prognostic scores are useful prognostic indicators for several types of cancer. The aim of this study was to evaluate whether the scores predict survival impact in unresectable perihilar cholangiocarcinoma. METHODS: The modified Glasgow Prognostic Score (mGPS), Neutrophil Lymphocyte Ratio (NLR), Platelet Lymphocyte Ratio, and Prognostic Nutritional Index, were retrospectively assessed in 219 patients with unresectable perihilar cholangiocarcinoma. RESULTS: Of the four scores evaluated, mGPS and NLR demonstrated prognostic value, whereas the remaining two systems did not. The median survival time (MST) of patients with a mGPS of 0 and NLR of 0 or 1 were significantly better than that of patients with a mGPS of 1 or 2 and NLR of 2 (12.3 vs. 4.8 months, P < 0.001, and 10.5 vs. 4.4 months, P = 0.001). Multivariate analysis revealed that both mGPS and NLR were independent prognostic factors. The combination of mGPS and NLR stratified survival well: the MST was 12.8 months in patients with a mGPS of 0 and NLR of 1 or 2, while only 3.0 months in patients with a mGPS of 1 or 2 and NLR of 2. CONCLUSIONS: Both mGPS and NLR are independent prognostic factors and pivotal in refining patient stratification in unresectable perihilar cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma improved survival elderly surgical intervention cholangiocarcinoma cca continues difficult disease diagnose treat optimal treatment includes resection histologically negative margins recent years advanced imaging including magnetic resonance cholangiography endoscopic ultrasound presumably improved accuracy determining resectability 2004 2009 total 61 patients cholangiocarcinoma evaluated resection majority men 37 ages ranged 29 87 years mean 67 years 31 per cent found obviously unresectable based imaging alone remaining 69 per cent underwent exploration time resection found unfeasible additional 25 per cent overall 56 unresectable although resection specimens grossly negative margins 37 per cent ultimately found microscopically positive overall 5 year actuarial survival patients undergoing resection 39 2 per cent survival difference positive negative margins despite advances diagnostic imaging half patients cca presenting surgical evaluation ultimately found unresectable however final determination still made time exploration even presence microscopic residual disease surgical intervention results improved survival aggressive stance toward surgical intervention patients cca remains justified stn","probabilities":0.9799733,"Title":"Intrahepatic Cholangiocarcinoma: Improved Survival In The Elderly With Surgical Intervention","Abstract":"Cholangiocarcinoma (CCA) continues to be a difficult disease to both diagnose and treat. Optimal treatment includes resection to histologically negative margins. In recent years, advanced imaging, including magnetic resonance cholangiography and endoscopic ultrasound, has presumably improved the accuracy of determining resectability. From 2004 to 2009, a total of 61 patients with cholangiocarcinoma were evaluated for resection. The majority were men (37) and ages ranged from 29 to 87 years (mean, 67 years). Only 31 per cent were found to be obviously unresectable based on imaging alone. The remaining 69 per cent underwent exploration, at which time resection was found unfeasible in an additional 25 per cent (overall 56% unresectable). Although all resection specimens had grossly negative margins, 37 per cent were ultimately found to be microscopically positive. The overall 5-year actuarial survival for patients undergoing resection was 39.2 per cent with no survival difference between those with positive and negative margins. Despite advances in diagnostic imaging, more than half of patients with CCA presenting for surgical evaluation are ultimately found to be unresectable. However, the final determination can still only be made at the time of exploration. Even in the presence of microscopic residual disease, surgical intervention results in improved survival. An aggressive stance toward surgical intervention in patients with CCA remains justified.","Source":"STN","category":"HUMAN","training_data":"Intrahepatic Cholangiocarcinoma: Improved Survival In The Elderly With Surgical Intervention Cholangiocarcinoma (CCA) continues to be a difficult disease to both diagnose and treat. Optimal treatment includes resection to histologically negative margins. In recent years, advanced imaging, including magnetic resonance cholangiography and endoscopic ultrasound, has presumably improved the accuracy of determining resectability. From 2004 to 2009, a total of 61 patients with cholangiocarcinoma were evaluated for resection. The majority were men (37) and ages ranged from 29 to 87 years (mean, 67 years). Only 31 per cent were found to be obviously unresectable based on imaging alone. The remaining 69 per cent underwent exploration, at which time resection was found unfeasible in an additional 25 per cent (overall 56% unresectable). Although all resection specimens had grossly negative margins, 37 per cent were ultimately found to be microscopically positive. The overall 5-year actuarial survival for patients undergoing resection was 39.2 per cent with no survival difference between those with positive and negative margins. Despite advances in diagnostic imaging, more than half of patients with CCA presenting for surgical evaluation are ultimately found to be unresectable. However, the final determination can still only be made at the time of exploration. Even in the presence of microscopic residual disease, surgical intervention results in improved survival. An aggressive stance toward surgical intervention in patients with CCA remains justified. STN","prediction_labels":"HUMAN"},{"cleaned":"apoptosis related protein 1 acts tumor suppressor cholangiocarcinoma cells inducing cell cycle arrest via downregulation cyclin dependent kinase subunits cholangiocarcinoma malignancy arising biliary tract associated high mortality due late diagnosis lack effective therapeutic approaches knowledge molecular alterations carcinogenesis cholangiocarcinoma limited previous study suggests apoptosis related protein 1 apr 1 involved cancer cell proliferation survival present study first detected expression pattern apr 1 human cholangiocarcinoma tissues effects forced apr 1 expression cell proliferation cell cycle progression cell cycle gene array analysis used identify downstream molecules regulated apr 1 expression levels evaluated human cholangiocarcinoma tissues showed apr 1 expression downregulated human cholangiocarcinoma tissues forced expression apr 1 inhibited cell proliferation cholangiocarcinoma cell line qbc939 induced g2 m phase arrest downregulation cell cycle related genes cyclin dependent kinase cdk 2 cyclin dependent kinase subunits cks 1 2 involved apr 1 induced cell cycle arrest furthermore found cdk2 cks1 2 expression levels elevated human cholangiocarcinoma tissues taken together data showed apr 1 plays crucial role cell proliferation controlling cell cycle progression implying tumor suppressor function apr 1 cholangiocarcinoma carcinogenesis thus present study provides rationale study underlying mechanisms apr 1 downregulation cholangiocarcinoma exploring potential diagnostic therapeutic targets stn","probabilities":0.9467213,"Title":"Apoptosis-Related Protein-1 Acts As A Tumor Suppressor In Cholangiocarcinoma Cells By Inducing Cell Cycle Arrest Via Downregulation Of Cyclin-Dependent Kinase Subunits","Abstract":"Cholangiocarcinoma, a malignancy arising from the biliary tract, is associated with high mortality due to the late diagnosis and lack of effective therapeutic approaches. Our knowledge of the molecular alterations during the carcinogenesis of cholangiocarcinoma is limited. Previous study suggests that apoptosis-related protein-1 (Apr-1) is involved in cancer cell proliferation and survival. In the present study, we first detected the expression pattern of Apr-1 in human cholangiocarcinoma tissues and the effects of forced Apr-1 expression on cell proliferation and cell cycle progression. Cell cycle gene array analysis was used to identify downstream molecules that were regulated by Apr-1, and their expression levels were further evaluated in human cholangiocarcinoma tissues. We showed that Apr-1 expression was downregulated in human cholangiocarcinoma tissues. Forced expression of Apr-1 inhibited cell proliferation of cholangiocarcinoma cell line QBC939 and induced G2/M phase arrest. Downregulation of cell cycle-related genes cyclin-dependent kinase (Cdk) 2, and cyclin-dependent kinase subunits (Cks) 1 and 2 was involved in Apr-1-induced cell cycle arrest. Furthermore, we found that Cdk2 and Cks1/2 expression levels were elevated in human cholangiocarcinoma tissues. Taken together, our data showed that Apr-1 plays a crucial role in cell proliferation by controlling cell cycle progression, implying a tumor-suppressor function of Apr-1 in cholangiocarcinoma carcinogenesis. Thus, the present study provides a rationale to further study the underlying mechanisms of Apr-1 downregulation in cholangiocarcinoma for exploring potential diagnostic and therapeutic targets.","Source":"STN","category":"ANIMAL","training_data":"Apoptosis-Related Protein-1 Acts As A Tumor Suppressor In Cholangiocarcinoma Cells By Inducing Cell Cycle Arrest Via Downregulation Of Cyclin-Dependent Kinase Subunits Cholangiocarcinoma, a malignancy arising from the biliary tract, is associated with high mortality due to the late diagnosis and lack of effective therapeutic approaches. Our knowledge of the molecular alterations during the carcinogenesis of cholangiocarcinoma is limited. Previous study suggests that apoptosis-related protein-1 (Apr-1) is involved in cancer cell proliferation and survival. In the present study, we first detected the expression pattern of Apr-1 in human cholangiocarcinoma tissues and the effects of forced Apr-1 expression on cell proliferation and cell cycle progression. Cell cycle gene array analysis was used to identify downstream molecules that were regulated by Apr-1, and their expression levels were further evaluated in human cholangiocarcinoma tissues. We showed that Apr-1 expression was downregulated in human cholangiocarcinoma tissues. Forced expression of Apr-1 inhibited cell proliferation of cholangiocarcinoma cell line QBC939 and induced G2/M phase arrest. Downregulation of cell cycle-related genes cyclin-dependent kinase (Cdk) 2, and cyclin-dependent kinase subunits (Cks) 1 and 2 was involved in Apr-1-induced cell cycle arrest. Furthermore, we found that Cdk2 and Cks1/2 expression levels were elevated in human cholangiocarcinoma tissues. Taken together, our data showed that Apr-1 plays a crucial role in cell proliferation by controlling cell cycle progression, implying a tumor-suppressor function of Apr-1 in cholangiocarcinoma carcinogenesis. Thus, the present study provides a rationale to further study the underlying mechanisms of Apr-1 downregulation in cholangiocarcinoma for exploring potential diagnostic and therapeutic targets. STN","prediction_labels":"ANIMAL"},{"cleaned":"racial ethnic age disparities incidence survival intrahepatic cholangiocarcinoma united states 1995 2014 introduction introduction despite reports increased incidence intrahepatic cholangiocarcinoma icca united states impact age influences race ethnicity clear disparities icca outcomes across various population subgroups also readily recognized due rarity cancer examined ethnic race age gender variations icca incidence survival using data surveillance epidemiology end results program 1995 2014 materials methods materials methods materials methods materials methods materials methods assessed age adjusted incidence rates average annual percentage change incidence hazard ratios hrs 95 confidence intervals cis cause icca specific mortality results results results results results overall 11 127 cases icca identified age adjusted incidence rate 0 92 per 100 000 incidence rate increased twofold 0 49 per 100 000 1995 1 49 per 100 000 2014 average annual rate increase 5 49 icca incidence rate higher among persons age 45 years older younger 45 years 1 71 vs 0 07 per 100 000 among males females 0 97 vs 0 88 per 100 000 among hispanics non hispanics 1 18 vs 0 89 per 100 000 compared non hispanics hispanics poorer 5 year cause mortality hr 1 11 95 ci 1 05 1 19 poorer icca specific mortality hr 1 15 95 ci 1 07 1 24 survival rates poor also individuals age 45 years older men blacks american indians alaska natives conclusion conclusion conclusion conclusion conclusion results demonstrate ethnic race age gender disparities icca incidence survival confirm continued increase icca incidence united states google scholar","probabilities":0.9799733,"Title":"Racial Ethnic And Age Disparities In Incidence And Survival Of Intrahepatic Cholangiocarcinoma In The United States; 1995-2014","Abstract":"Introduction. Introduction. Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014). Materials and methods. Materials and methods. Materials and methods. Materials and methods. Materials and methods. We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality. Results. Results. Results. Results. Results. Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year all-cause mortality (HR = 1.11, 95%CI: 1.05–1.19) and poorer iCCA-specific mortality (HR = 1.15, 95%CI: 1.07–1.24). Survival rates were poor also for individuals age 45 years or older, men, Blacks, and American Indians/Alaska Natives. Conclusion. Conclusion. Conclusion. Conclusion. Conclusion. The results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States.","Source":"Google Scholar","category":"HUMAN","training_data":"Racial Ethnic And Age Disparities In Incidence And Survival Of Intrahepatic Cholangiocarcinoma In The United States; 1995-2014 Introduction. Introduction. Despite reports of increased incidence of intrahepatic cholangiocarcinoma (iCCA) in the United States, the impact of age or influences of race and ethnicity are not clear. Disparities in iCCA outcomes across various population subgroups also are not readily recognized due to the rarity of this cancer. We examined ethnic, race, age, and gender variations in iCCA incidence and survival using data from the Surveillance, Epidemiology, and End Results Program (1995-2014). Materials and methods. Materials and methods. Materials and methods. Materials and methods. Materials and methods. We assessed age-adjusted incidence rates, average annual percentage change in incidence, and hazard ratios (HRs) with 95% confidence intervals (CIs) for all-cause and iCCA-specific mortality. Results. Results. Results. Results. Results. Overall, 11,127 cases of iCCA were identified, with an age-adjusted incidence rate of 0.92 per 100,000. The incidence rate increased twofold, from 0.49 per 100,000 in 1995 to 1.49 per 100,000 in 2014, with an average annual rate of increase of 5.49%. The iCCA incidence rate was higher among persons age 45 years or older than those younger than 45 years (1.71 vs. 0.07 per 100,000), among males than females (0.97 vs. 0.88 per 100,000) and among Hispanics than non-Hispanics (1.18 vs. 0.89 per 100,000). Compared to non-Hispanics, Hispanics had poorer 5-year all-cause mortality (HR = 1.11, 95%CI: 1.05–1.19) and poorer iCCA-specific mortality (HR = 1.15, 95%CI: 1.07–1.24). Survival rates were poor also for individuals age 45 years or older, men, Blacks, and American Indians/Alaska Natives. Conclusion. Conclusion. Conclusion. Conclusion. Conclusion. The results demonstrate ethnic, race, age and gender disparities in iCCA incidence and survival, and confirm continued increase in iCCA incidence in the United States. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"histone deacetylase inhibitors inhibit proliferation gallbladder carcinoma cells suppressing akt mtor signaling gallbladder carcinoma aggressive malignancy high mortality mainly due limited potential curative resection resistance chemotherapeutic agents show histone deacetylase inhibitors hdacis trichostatin tsa suberoylanilide hydroxamic acid saha reduce proliferation induce apoptosis gallbladder carcinoma cells suppressing akt mammalian target rapamycin mtor signaling gallbladder carcinoma sgc 996 cells treated different concentrations tsa saha different lengths time cell proliferation morphology assessed mtt assay microscopy respectively cell cycle distribution cell apoptosis analyzed flow cytometry western blotting used detect proteins related apoptosis cell cycle akt mtor signaling pathway data showed tsa saha reduced sgc 996 cell viability arrested cell cycle g1 phase dose time dependent manner tsa saha promoted apoptosis sgc 996 cells regulated expression cyclin d1 c myc bmi1 decreased phosphorylation akt mtor p70s6k1 s6 4e bp1 additionally mtor inhibitor rapamycin reduced cell viability tsa saha treated sgc 996 cells phosphorylation mtor whereas mtor activator 1 2 dioctanoyl sn glycero 3 phosphate c8 pa exerted opposite influence results demonstrate histone deacetylase inhibitors hdacis suppress proliferation gallbladder carcinoma cell via inhibition akt mtor signaling findings offer mechanistic rationale application hdacis gallbladder carcinoma treatment stn","probabilities":0.9467213,"Title":"Histone Deacetylase Inhibitors Inhibit The Proliferation Of Gallbladder Carcinoma Cells By Suppressing Akt/Mtor Signaling","Abstract":"Gallbladder carcinoma is an aggressive malignancy with high mortality mainly due to the limited potential for curative resection and its resistance to chemotherapeutic agents. Here, we show that the histone deacetylase inhibitors (HDACIs) trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA) reduce the proliferation and induce apoptosis of gallbladder carcinoma cells by suppressing the AKT/mammalian target of rapamycin (mTOR) signaling. Gallbladder carcinoma SGC-996 cells were treated with different concentrations of TSA and SAHA for different lengths of time. Cell proliferation and morphology were assessed with MTT assay and microscopy, respectively. Cell cycle distribution and cell apoptosis were analyzed with flow cytometry. Western blotting was used to detect the proteins related to apoptosis, cell cycle, and the AKT/mTOR signaling pathway. Our data showed that TSA and SAHA reduced SGC-996 cell viability and arrested cell cycle at the G1 phase in a dose- and time-dependent manner. TSA and SAHA promoted apoptosis of SGC-996 cells, down-regulated the expression of cyclin D1, c-Myc and Bmi1, and decreased the phosphorylation of AKT, mTOR p70S6K1, S6 and 4E-BP1. Additionally, the mTOR inhibitor rapamycin further reduced the cell viability of TSA- and SAHA-treated SGC-996 cells and the phosphorylation of mTOR, whereas the mTOR activator 1,2-dioctanoyl-sn-glycero-3-phosphate (C8-PA) exerted the opposite influence. Our results demonstrate that histone deacetylase inhibitors (HDACIs) suppress the proliferation of gallbladder carcinoma cell via inhibition of AKT/mTOR signaling. These findings offer a mechanistic rationale for the application of HDACIs in gallbladder carcinoma treatment.","Source":"STN","category":"ANIMAL","training_data":"Histone Deacetylase Inhibitors Inhibit The Proliferation Of Gallbladder Carcinoma Cells By Suppressing Akt/Mtor Signaling Gallbladder carcinoma is an aggressive malignancy with high mortality mainly due to the limited potential for curative resection and its resistance to chemotherapeutic agents. Here, we show that the histone deacetylase inhibitors (HDACIs) trichostatin-A (TSA) and suberoylanilide hydroxamic acid (SAHA) reduce the proliferation and induce apoptosis of gallbladder carcinoma cells by suppressing the AKT/mammalian target of rapamycin (mTOR) signaling. Gallbladder carcinoma SGC-996 cells were treated with different concentrations of TSA and SAHA for different lengths of time. Cell proliferation and morphology were assessed with MTT assay and microscopy, respectively. Cell cycle distribution and cell apoptosis were analyzed with flow cytometry. Western blotting was used to detect the proteins related to apoptosis, cell cycle, and the AKT/mTOR signaling pathway. Our data showed that TSA and SAHA reduced SGC-996 cell viability and arrested cell cycle at the G1 phase in a dose- and time-dependent manner. TSA and SAHA promoted apoptosis of SGC-996 cells, down-regulated the expression of cyclin D1, c-Myc and Bmi1, and decreased the phosphorylation of AKT, mTOR p70S6K1, S6 and 4E-BP1. Additionally, the mTOR inhibitor rapamycin further reduced the cell viability of TSA- and SAHA-treated SGC-996 cells and the phosphorylation of mTOR, whereas the mTOR activator 1,2-dioctanoyl-sn-glycero-3-phosphate (C8-PA) exerted the opposite influence. Our results demonstrate that histone deacetylase inhibitors (HDACIs) suppress the proliferation of gallbladder carcinoma cell via inhibition of AKT/mTOR signaling. These findings offer a mechanistic rationale for the application of HDACIs in gallbladder carcinoma treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"downsizing chemotherapy initially unresectable locally advanced biliary tract cancer patients treated gemcitabine plus cisplatin combination therapy followed radical surgery backgound treated patients initially unresectable locally advanced biliary tract cancer btc administering gemcitabine found surgical resection became feasible downsized patients aim study investigate usefulness downsizing combination chemotherapy using gemcitabine plus cisplatin treat initially unresectable locally advanced btc methods subjects study 150 consecutive patients treated btc october 2011 april 2014 downsizing chemotherapy carried 39 patients 26 0 whose lesions unresectable locally advanced btc results reduction tumor size downsizing chemotherapy seen 18 patients surgical resection performed 10 39 patients 25 6 median survival time patients surgical resection following downsizing chemotherapy chemotherapy alone 17 9 12 4 months respectively p 0 0378 according historical comparison gemcitabine gemcitabine plus cisplatin chemotherapy significant difference overall survival however significant difference pathologic response rate grade iii higher patients gemcitabine plus cisplatin chemotherapy compared gemcitabine monotherapy conclusions preoperative downsizing chemotherapy gemcitabine plus cisplatin provides longer survival conversion surgical resection patients initially unresectable locally advanced btc may potential disease eradication new multidisciplinary approach initially unresectable locally advanced btc pubmed","probabilities":0.9799733,"Title":"Downsizing Chemotherapy for Initially Unresectable Locally Advanced Biliary Tract Cancer Patients Treated with Gemcitabine Plus Cisplatin Combination Therapy Followed by Radical Surgery","Abstract":"BACKGOUND: We have treated patients with initially unresectable locally advanced biliary tract cancer (BTC) by administering gemcitabine and have found that surgical resection became feasible in some downsized patients. The aim of this study was to investigate the usefulness of downsizing combination chemotherapy using gemcitabine plus cisplatin to treat initially unresectable locally advanced BTC. METHODS: The subjects of the study were 150 consecutive patients who were treated for BTC between October 2011 and April 2014. Downsizing chemotherapy was carried out for 39 patients (26.0 %) whose lesions were unresectable because of locally advanced BTC. RESULTS: Reduction in tumor size with downsizing chemotherapy was seen in 18 patients, and surgical resection was performed in 10 of 39 patients (25.6 %). Median survival time in patients with surgical resection following downsizing chemotherapy and those with chemotherapy alone was 17.9 and 12.4 months, respectively (p = 0.0378). According to the historical comparison between gemcitabine and gemcitabine plus cisplatin chemotherapy, there is no significant difference in overall survival. However, there was a significant difference for the pathologic response rate (≥Grade III) to be higher in patients with gemcitabine plus cisplatin chemotherapy compared with gemcitabine monotherapy. CONCLUSIONS: Preoperative downsizing chemotherapy with gemcitabine plus cisplatin provides longer survival by the conversion to the surgical resection in patients with initially unresectable locally advanced BTC. It may have the potential for disease eradication as a new multidisciplinary approach for initially unresectable locally advanced BTC.","Source":"PubMed","category":"HUMAN","training_data":"Downsizing Chemotherapy for Initially Unresectable Locally Advanced Biliary Tract Cancer Patients Treated with Gemcitabine Plus Cisplatin Combination Therapy Followed by Radical Surgery BACKGOUND: We have treated patients with initially unresectable locally advanced biliary tract cancer (BTC) by administering gemcitabine and have found that surgical resection became feasible in some downsized patients. The aim of this study was to investigate the usefulness of downsizing combination chemotherapy using gemcitabine plus cisplatin to treat initially unresectable locally advanced BTC. METHODS: The subjects of the study were 150 consecutive patients who were treated for BTC between October 2011 and April 2014. Downsizing chemotherapy was carried out for 39 patients (26.0 %) whose lesions were unresectable because of locally advanced BTC. RESULTS: Reduction in tumor size with downsizing chemotherapy was seen in 18 patients, and surgical resection was performed in 10 of 39 patients (25.6 %). Median survival time in patients with surgical resection following downsizing chemotherapy and those with chemotherapy alone was 17.9 and 12.4 months, respectively (p = 0.0378). According to the historical comparison between gemcitabine and gemcitabine plus cisplatin chemotherapy, there is no significant difference in overall survival. However, there was a significant difference for the pathologic response rate (≥Grade III) to be higher in patients with gemcitabine plus cisplatin chemotherapy compared with gemcitabine monotherapy. CONCLUSIONS: Preoperative downsizing chemotherapy with gemcitabine plus cisplatin provides longer survival by the conversion to the surgical resection in patients with initially unresectable locally advanced BTC. It may have the potential for disease eradication as a new multidisciplinary approach for initially unresectable locally advanced BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"malignancies patients inflammatory bowel disease nationwide register study finland objective patients inflammatory bowel disease ibd increased risk certain cancers assessed long term risks malignancies among patients ibd finland methods total 21 964 patients ibd 16 649 uc 5315 cd database social insurance institution diagnosed periods 1987 1993 2000 2007 followed end 2010 linkage nationwide finnish cancer registry numbers cancers observed compared expected general population expressed standardized incidence ratio sir results overall male patients cd uc slightly increased risk malignancies patients uc found increased risk colon sir 1 81 95 confidence interval 1 46 2 21 rectal 1 76 1 35 2 25 biliary tract 7 26 4 37 11 1 thyroid cancers 1 93 1 28 2 79 risk colorectal cancer crc highest among youngest uc patients patients cd significantly increased sir cancers small intestine 9 97 4 30 19 6 anus 9 51 1 96 27 8 biliary tract 4 93 1 02 14 4 also myeloma 2 84 1 14 5 85 addition risk basal cell skin cancer increased ibd 1 29 1 16 1 43 males uc slightly decreased risk lung prostate cancers conclusions incidence cancer among male patients cd cu higher general population patients uc increased risk crc biliary tract cancers crc risk highest youngest patients pubmed","probabilities":0.962963,"Title":"Malignancies in patients with inflammatory bowel disease: a nationwide register study in Finland","Abstract":"OBJECTIVE. Patients with inflammatory bowel disease (IBD) are at increased risk of certain cancers. We assessed the long-term risks of malignancies among patients with IBD in Finland. METHODS. A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the database of the Social Insurance Institution were diagnosed in the periods 1987-1993 and 2000-2007 and followed up to the end of 2010 in a linkage with the nationwide Finnish Cancer Registry. The numbers of cancers observed were compared to those expected in general population and expressed as a standardized incidence ratio (SIR). RESULTS. Overall, male patients with CD and UC had a slightly increased risk of malignancies. Patients with UC were found to have an increased risk of colon (SIR 1.81, 95% confidence interval 1.46-2.21), rectal (1.76, 1.35-2.25), biliary tract (7.26, 4.37-11.1), and thyroid cancers (1.93, 1.28-2.79). The risk of colorectal cancer (CRC) was highest among the youngest UC patients. Patients with CD had a significantly increased SIR for cancers of the small intestine (9.97, 4.30-19.6), anus (9.51, 1.96-27.8), and biliary tract (4.93, 1.02-14.4), and also for myeloma (2.84, 1.14-5.85). In addition, the risk of basal cell skin cancer was increased in IBD (1.29, 1.16-1.43). Males with UC had a slightly decreased risk of lung and prostate cancers. CONCLUSIONS. The incidence of cancer among male patients with CD and CU was higher than that in general population. Patients with UC are at increased risk for CRC and biliary tract cancers. CRC risk was highest in the youngest patients.","Source":"PubMed","category":"HUMAN","training_data":"Malignancies in patients with inflammatory bowel disease: a nationwide register study in Finland OBJECTIVE. Patients with inflammatory bowel disease (IBD) are at increased risk of certain cancers. We assessed the long-term risks of malignancies among patients with IBD in Finland. METHODS. A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the database of the Social Insurance Institution were diagnosed in the periods 1987-1993 and 2000-2007 and followed up to the end of 2010 in a linkage with the nationwide Finnish Cancer Registry. The numbers of cancers observed were compared to those expected in general population and expressed as a standardized incidence ratio (SIR). RESULTS. Overall, male patients with CD and UC had a slightly increased risk of malignancies. Patients with UC were found to have an increased risk of colon (SIR 1.81, 95% confidence interval 1.46-2.21), rectal (1.76, 1.35-2.25), biliary tract (7.26, 4.37-11.1), and thyroid cancers (1.93, 1.28-2.79). The risk of colorectal cancer (CRC) was highest among the youngest UC patients. Patients with CD had a significantly increased SIR for cancers of the small intestine (9.97, 4.30-19.6), anus (9.51, 1.96-27.8), and biliary tract (4.93, 1.02-14.4), and also for myeloma (2.84, 1.14-5.85). In addition, the risk of basal cell skin cancer was increased in IBD (1.29, 1.16-1.43). Males with UC had a slightly decreased risk of lung and prostate cancers. CONCLUSIONS. The incidence of cancer among male patients with CD and CU was higher than that in general population. Patients with UC are at increased risk for CRC and biliary tract cancers. CRC risk was highest in the youngest patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"polypoid lesions gallbladder consecutive series 2631 patients single center experience background challenges diagnosis polypoid gallbladder lesion plg due low sensibility se ultrasound scan us selection criteria patients plg addressed surgical treatment followup yet fully defined materials methods retrospective observational study conducted 2631 patients 1175 44 6 m mean age 56 years 1456 55 4 f mean age 46 years underwent laparoscopic open cholecystectomy results us diagnosis plg placed 38 2631 1 4 patients histological examination polyps identified 68 2631 2 6 patients associated biliary lithiasis 28 2631 1 1 cases us comparison ultrasound diagnosis burdened false positives 8 38 21 false negatives 38 2631 1 45 se 44 95 c 32 2 55 7 histological incidence gall bladder cancer gbc 0 38 10 2631 discussion us survey underestimated incidence plg compared histological finding p 0 021 female gender shown specific risk factor benign malignant plg non polypoid mucosal lesions p 0 041 parietal lesion size 0 5cm exclude neoplastic nature currently prevention diagnosis gbc based early detection treatment potentially evolutionary polypoid lesions period 15 years conclusions probably early cholecystectomy patients plg diameter 1cm isolated associated lithiasis symptomatic asymptomatic contribute reduction incidence gbc key words cholecystectomy gallbladder polyps gallbladder cancer ultrasound scan pubmed","probabilities":0.9799733,"Title":"Polypoid lesions of the gallbladder in a consecutive series of 2631 patients A single-center experience","Abstract":"BACKGROUND: Challenges in the diagnosis of polypoid gallbladder lesion (PLG) is due to the low sensibility (SE) of ultrasound scan (US), and the selection criteria of patients with PLG to be addressed to surgical treatment or followup are not yet fully defined. MATERIALS AND METHODS: Retrospective observational study was conducted on 2631 patients, 1175(44.6%) M, mean age 56 years, 1456(55.4%) F, mean age 46 years, who underwent laparoscopic and open cholecystectomy. RESULTS: The US diagnosis for PLG was placed in 38/2631(1.4%) patients. On histological examination (HE) the polyps were identified in 68/2631(2.6%) patients and it was associated with biliary lithiasis in 28/2631 (1.1%) cases. From the US and HE comparison, the ultrasound diagnosis was burdened by false positives (8/38; 21%) and false negatives (38/2631;1.45%), with SE 44% (95% c.i.:32.2-55.7). The histological incidence of gall bladder cancer (GBC) was 0.38%(10/2631). DISCUSSION: US survey underestimated the incidence of PLG compared to the histological finding (p=0.021). Female gender has been shown to be a specific risk factor for benign and malignant PLG and non-polypoid mucosal lesions (p=0.041). The parietal lesion size <0.5cm does not exclude the neoplastic nature. Currently the prevention and diagnosis of GBC is based on the early detection and treatment of potentially evolutionary polypoid lesions over a period of about 15 years. CONCLUSIONS: It is probably that early cholecystectomy in all the patients with PLG of diameter <1cm, isolated or associated with lithiasis, symptomatic and asymptomatic, can contribute to the reduction of the incidence of GBC. KEY WORDS: Cholecystectomy, Gallbladder polyps, Gallbladder cancer, Ultrasound scan.","Source":"PubMed","category":"HUMAN","training_data":"Polypoid lesions of the gallbladder in a consecutive series of 2631 patients A single-center experience BACKGROUND: Challenges in the diagnosis of polypoid gallbladder lesion (PLG) is due to the low sensibility (SE) of ultrasound scan (US), and the selection criteria of patients with PLG to be addressed to surgical treatment or followup are not yet fully defined. MATERIALS AND METHODS: Retrospective observational study was conducted on 2631 patients, 1175(44.6%) M, mean age 56 years, 1456(55.4%) F, mean age 46 years, who underwent laparoscopic and open cholecystectomy. RESULTS: The US diagnosis for PLG was placed in 38/2631(1.4%) patients. On histological examination (HE) the polyps were identified in 68/2631(2.6%) patients and it was associated with biliary lithiasis in 28/2631 (1.1%) cases. From the US and HE comparison, the ultrasound diagnosis was burdened by false positives (8/38; 21%) and false negatives (38/2631;1.45%), with SE 44% (95% c.i.:32.2-55.7). The histological incidence of gall bladder cancer (GBC) was 0.38%(10/2631). DISCUSSION: US survey underestimated the incidence of PLG compared to the histological finding (p=0.021). Female gender has been shown to be a specific risk factor for benign and malignant PLG and non-polypoid mucosal lesions (p=0.041). The parietal lesion size <0.5cm does not exclude the neoplastic nature. Currently the prevention and diagnosis of GBC is based on the early detection and treatment of potentially evolutionary polypoid lesions over a period of about 15 years. CONCLUSIONS: It is probably that early cholecystectomy in all the patients with PLG of diameter <1cm, isolated or associated with lithiasis, symptomatic and asymptomatic, can contribute to the reduction of the incidence of GBC. KEY WORDS: Cholecystectomy, Gallbladder polyps, Gallbladder cancer, Ultrasound scan. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance tumor stroma ratio gallbladder cancer recent years tumor stroma ratio tsr attracted increasing attention independent prognostic factor several solid tumors however importance stromal compartment investigated yet gallbladder cancer gbc objective study investigate prognostic value tsr gbc relationship tsr known prognostic parameters total 51 patients underwent operations gallbladder carcinoma selected study tsr determined haematoxylin eosin h et e stained sections two independent investigators stromal ratio groups classified stroma poor ratio stroma 50 mann whitney test chi squared test kaplan meier method cox proportional hazards model used analyze data median survival time patients stroma rich group 6 00 months 95 ci 4 47 7 54 contrast stroma poor group median survival time 17 00 months 95 ci 3 64 30 36 3 year overall survival rate 19 7 stroma poor group 7 2 stroma rich group patients stroma rich tumors worse prognosis stroma poor tumors log rank p 0 004 according univariate analysis tsr differentiation grade ptnm stage operative methods shown related overall survival os statistical significance hazard ratio hr tsr 2 428 95 ci 1 29 4 58 p 0 006 however tsr prove independent prognostic factor multivariate analysis study demonstrated tumor stroma ratio tsr important prognostic parameter gallbladder cancer gbc stroma rich tumors associated poor overall survival pubmed","probabilities":0.9799733,"Title":"Prognostic significance of the tumor-stroma ratio in gallbladder cancer","Abstract":"In recent years, the tumor-stroma ratio (TSR) has attracted increasing attention as an independent prognostic factor for several solid tumors. However, the importance of the stromal compartment has not been investigated yet in gallbladder cancer (GBC). The objective of this study is to investigate the prognostic value of TSR in GBC and the relationship between TSR and other known prognostic parameters. A total of 51 patients who underwent operations for gallbladder carcinoma were selected for this study. TSR was determined on haematoxylin and eosin (H et E)-stained sections by two independent investigators. Stromal ratio groups were classified as stroma-poor (ratio of stroma 50%). The Mann-Whitney test, the Chi-squared test, the Kaplan-Meier method, and the Cox proportional hazards model were used to analyze the data. The median survival time for patients in the stroma-rich group was 6.00 months (95% CI, 4.47-7.54). In contrast, for the stroma-poor group, the median survival time was 17.00 months (95% CI, 3.64-30.36). The 3-year overall survival rate was 19.7% in the stroma-poor group and 7.2% in the stroma-rich group. Patients with stroma-rich tumors had a worse prognosis than those with stroma-poor tumors (log-rank P = 0.004). According to the univariate analysis, the TSR, differentiation grade, pTNM stage, and operative methods were shown to be related to overall survival (OS) with statistical significance. The hazard ratio (HR) of TSR was 2.428 (95% CI, 1.29-4.58; P = 0.006). However, the TSR did not prove to be an independent prognostic factor in the multivariate analysis. Our study demonstrated that the tumor-stroma ratio (TSR) is an important prognostic parameter for gallbladder cancer (GBC). Stroma-rich tumors were associated with poor overall survival.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of the tumor-stroma ratio in gallbladder cancer In recent years, the tumor-stroma ratio (TSR) has attracted increasing attention as an independent prognostic factor for several solid tumors. However, the importance of the stromal compartment has not been investigated yet in gallbladder cancer (GBC). The objective of this study is to investigate the prognostic value of TSR in GBC and the relationship between TSR and other known prognostic parameters. A total of 51 patients who underwent operations for gallbladder carcinoma were selected for this study. TSR was determined on haematoxylin and eosin (H et E)-stained sections by two independent investigators. Stromal ratio groups were classified as stroma-poor (ratio of stroma 50%). The Mann-Whitney test, the Chi-squared test, the Kaplan-Meier method, and the Cox proportional hazards model were used to analyze the data. The median survival time for patients in the stroma-rich group was 6.00 months (95% CI, 4.47-7.54). In contrast, for the stroma-poor group, the median survival time was 17.00 months (95% CI, 3.64-30.36). The 3-year overall survival rate was 19.7% in the stroma-poor group and 7.2% in the stroma-rich group. Patients with stroma-rich tumors had a worse prognosis than those with stroma-poor tumors (log-rank P = 0.004). According to the univariate analysis, the TSR, differentiation grade, pTNM stage, and operative methods were shown to be related to overall survival (OS) with statistical significance. The hazard ratio (HR) of TSR was 2.428 (95% CI, 1.29-4.58; P = 0.006). However, the TSR did not prove to be an independent prognostic factor in the multivariate analysis. Our study demonstrated that the tumor-stroma ratio (TSR) is an important prognostic parameter for gallbladder cancer (GBC). Stroma-rich tumors were associated with poor overall survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison yttrium 90 therapy unresectable liver metastasis glass versus biocompatible resin microspheres objectives yttrium 90 radioembolization hepatic intra arterial based therapy using glass resin based microspheres carriers deliver high dose radiation tumors maximize dose minimizing collateral damage study aimed compare safety efficacy glass therasphere versus resin selective internal radiation spheres sir spheres y 90 treatment intrahepatic metastatic disease methods review prospectively collected institutional review board approved database conducted identify patients underwent y 90 therapy excluding hepatocellular carcinoma hcc results 119 patients 79 received sir spheres 40 received therasphere therapy intrahepatic cholangiocarcinoma mean survival 10 6 months sir spheres group compared 29 2 months therasphere group log rank 0 05 colorectal cancer crc mean survival 16 3 months sir spheres therapy 26 8 therasphere therapy log rank 0 097 documented severe grade 3 side effects therasphere group compared 14 patients experienced side effects sir spheres group conclusions therasphere microsphere appears superior sir spheres treating non hcc intrahepatic malignancy however patient selection better multi disciplinary care may play role differences continued studies combination therapies hepatic malignancies critical long term success sustainability y 90 therapy google scholar","probabilities":0.9799733,"Title":"Comparison Of Yttrium-90 Therapy For Unresectable Liver Metastasis: Glass Versus Biocompatible Resin Microspheres","Abstract":"Objectives\nYttrium-90 radioembolization is a hepatic intra-arterial-based therapy using glass- or resin-based microspheres as carriers to deliver high-dose radiation to tumors to maximize dose while minimizing collateral damage. This study aimed to compare the safety and efficacy of glass (TheraSphere) versus resin (Selective Internal Radiation Spheres, SIR-Spheres) Y-90 in the treatment of intrahepatic metastatic disease.\nMethods\nA review of a prospectively collected, institutional review board-approved database was conducted to identify patients who underwent Y-90 therapy, excluding those with hepatocellular carcinoma (HCC).\nResults\nOf 119 patients, 79 received SIR-Spheres and 40 received TheraSphere therapy. For intrahepatic cholangiocarcinoma, mean survival was 10.6 months in the SIR-Spheres group compared to 29.2 months in the TheraSphere group (log-rank 0.05). In colorectal cancer (CRC), mean survival was 16.3 months for SIR-Spheres therapy and 26.8 for TheraSphere therapy (log-rank 0.097). There were no documented severe (grade 3) side effects in the TheraSphere group compared to 14 % of patients who experienced side effects in the SIR-Spheres group.\nConclusions\nTheraSphere microsphere appears superior to SIR-Spheres in treating non-HCC intrahepatic malignancy. However, patient selection and better multi-disciplinary care may play a role in these differences. Continued studies in combination therapies for all hepatic malignancies is critical to the long-term success and sustainability of Y-90 therapy.","Source":"Google Scholar","category":"HUMAN","training_data":"Comparison Of Yttrium-90 Therapy For Unresectable Liver Metastasis: Glass Versus Biocompatible Resin Microspheres Objectives\nYttrium-90 radioembolization is a hepatic intra-arterial-based therapy using glass- or resin-based microspheres as carriers to deliver high-dose radiation to tumors to maximize dose while minimizing collateral damage. This study aimed to compare the safety and efficacy of glass (TheraSphere) versus resin (Selective Internal Radiation Spheres, SIR-Spheres) Y-90 in the treatment of intrahepatic metastatic disease.\nMethods\nA review of a prospectively collected, institutional review board-approved database was conducted to identify patients who underwent Y-90 therapy, excluding those with hepatocellular carcinoma (HCC).\nResults\nOf 119 patients, 79 received SIR-Spheres and 40 received TheraSphere therapy. For intrahepatic cholangiocarcinoma, mean survival was 10.6 months in the SIR-Spheres group compared to 29.2 months in the TheraSphere group (log-rank 0.05). In colorectal cancer (CRC), mean survival was 16.3 months for SIR-Spheres therapy and 26.8 for TheraSphere therapy (log-rank 0.097). There were no documented severe (grade 3) side effects in the TheraSphere group compared to 14 % of patients who experienced side effects in the SIR-Spheres group.\nConclusions\nTheraSphere microsphere appears superior to SIR-Spheres in treating non-HCC intrahepatic malignancy. However, patient selection and better multi-disciplinary care may play a role in these differences. Continued studies in combination therapies for all hepatic malignancies is critical to the long-term success and sustainability of Y-90 therapy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"diagnosis differential diagnosis epidemiology primary sclerosing cholangitis according recent guidelines primary sclerosing cholangitis psc diagnosed patient cholestatic liver enzyme profile characteristic bile duct changes imaging secondary causes sclerosing cholangitis excluded patients clinical suspicion normal cholangiography liver biopsy indicated establish diagnosis small duct psc several disease entities igg4 associated cholangitis iac cholangiocarcinoma cca secondary causes sclerosing cholangitis choledocholithiasis aids cholangiopathy ischemia surgical bile duct trauma mast cell cholangiopathy mimic psc iac differentiated psc applying hisort criteria including serum igg4 level cases serum igg4 less 2 uln ratio igg4 igg1 0 24 indicative iac choledocholithiasis recurrent cholangitis cause sclerosing cholangitis pose conundrum since psc associated increased prevalence gallstones epidemiology psc worldwide poorly described incidence prevalence rates vary 0 1 3 0 16 2 per 100 000 inhabitants respectively however figures based population based cohorts recent large population based cohort netherlands reported incidence 0 5 prevalence 6 100 000 approximately 10 fulfil criteria small duct psc diagnosis psc concurrent inflammatory bowel disease ibd primarily ulcerative colitis crohn colitis present 50 increasing 80 10 years diagnosis conversely 3 ibd patients develop psc psc predisposes malignancy estimated cumulative risk developing cca 30 years 20 colorectal carcinoma psc colitis patients estimated cumulative risk 30 years 13 pubmed","probabilities":0.962963,"Title":"Diagnosis, Differential Diagnosis, and Epidemiology of Primary Sclerosing Cholangitis","Abstract":"According to recent guidelines, primary sclerosing cholangitis (PSC) is diagnosed when a patient has a cholestatic liver enzyme profile, characteristic bile duct changes on imaging, and when secondary causes of sclerosing cholangitis are excluded. In patients with a clinical suspicion but normal cholangiography, a liver biopsy is indicated to establish a diagnosis of small duct PSC. Several other disease entities such as IgG4-associated cholangitis (IAC), cholangiocarcinoma (CCA), and secondary causes of sclerosing cholangitis such as choledocholithiasis, AIDS-cholangiopathy, ischemia, surgical bile duct trauma, or mast cell cholangiopathy can mimic PSC. IAC can be differentiated from PSC by applying the HISORt criteria including the serum IgG4 level. In cases where serum IgG4 is less than 2 × ULN, the ratio of IgG4/IgG1 >0.24 is indicative for IAC. Choledocholithiasis with recurrent cholangitis as a cause of sclerosing cholangitis can pose a conundrum, since PSC itself is associated with an increased prevalence of gallstones. The epidemiology of PSC worldwide has been poorly described. Incidence and prevalence rates vary from 0-1.3 and 0-16.2 per 100,000 inhabitants respectively. However, these figures are not based on population-based cohorts. A recent large population-based cohort from the Netherlands reported an incidence of 0.5 and a prevalence of 6/100,000. Approximately 10% fulfil the criteria for small duct PSC. At diagnosis of PSC, concurrent inflammatory bowel disease (IBD), primarily ulcerative colitis or Crohn's colitis is present in 50%, but increasing to 80%, 10 years or more after diagnosis. Conversely, 3% of IBD patients will develop PSC. PSC predisposes to malignancy. The estimated cumulative risk of developing CCA after 30 years is 20%. For colorectal carcinoma in PSC/colitis patients, the estimated cumulative risk at 30 years is 13%.","Source":"PubMed","category":"HUMAN","training_data":"Diagnosis, Differential Diagnosis, and Epidemiology of Primary Sclerosing Cholangitis According to recent guidelines, primary sclerosing cholangitis (PSC) is diagnosed when a patient has a cholestatic liver enzyme profile, characteristic bile duct changes on imaging, and when secondary causes of sclerosing cholangitis are excluded. In patients with a clinical suspicion but normal cholangiography, a liver biopsy is indicated to establish a diagnosis of small duct PSC. Several other disease entities such as IgG4-associated cholangitis (IAC), cholangiocarcinoma (CCA), and secondary causes of sclerosing cholangitis such as choledocholithiasis, AIDS-cholangiopathy, ischemia, surgical bile duct trauma, or mast cell cholangiopathy can mimic PSC. IAC can be differentiated from PSC by applying the HISORt criteria including the serum IgG4 level. In cases where serum IgG4 is less than 2 × ULN, the ratio of IgG4/IgG1 >0.24 is indicative for IAC. Choledocholithiasis with recurrent cholangitis as a cause of sclerosing cholangitis can pose a conundrum, since PSC itself is associated with an increased prevalence of gallstones. The epidemiology of PSC worldwide has been poorly described. Incidence and prevalence rates vary from 0-1.3 and 0-16.2 per 100,000 inhabitants respectively. However, these figures are not based on population-based cohorts. A recent large population-based cohort from the Netherlands reported an incidence of 0.5 and a prevalence of 6/100,000. Approximately 10% fulfil the criteria for small duct PSC. At diagnosis of PSC, concurrent inflammatory bowel disease (IBD), primarily ulcerative colitis or Crohn's colitis is present in 50%, but increasing to 80%, 10 years or more after diagnosis. Conversely, 3% of IBD patients will develop PSC. PSC predisposes to malignancy. The estimated cumulative risk of developing CCA after 30 years is 20%. For colorectal carcinoma in PSC/colitis patients, the estimated cumulative risk at 30 years is 13%. PubMed","prediction_labels":"HUMAN"},{"cleaned":"mirna profiling diagnosis prognosis stratification cancer treatment cholangiocarcinoma cholangiocarcinoma cca lethal malignancy originating biliary tract epithelium patients diagnosed advanced stage even resection curative intent prognosis remains poor previous studies reported evolving role mirnas novel biomarkers cancer diagnosis prognostication chemotherapy response various mirnas mir 21 mir 26 mir 122 mir 150 identified possible blood based biomarkers noninvasive diagnosis cca moreover epithelial mesenchymal transition emt angiogenesis associated mirnas implicated tumor cell dissemination able determine clinical outcome fact mirnas involved cell survival might even determine chemotherapy response review provides overview known mirnas cca specific biomarkers pubmed","probabilities":0.962963,"Title":"miRNA profiling for diagnosis, prognosis and stratification of cancer treatment in cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a lethal malignancy originating from the biliary tract epithelium. Most patients are diagnosed at an advanced stage. Even after resection with curative intent, prognosis remains poor. Previous studies have reported the evolving role of miRNAs as novel biomarkers in cancer diagnosis, prognostication and chemotherapy response. Various miRNAs, such as miR-21, miR-26, miR-122 and miR-150, have been identified as possible blood-based biomarkers for noninvasive diagnosis of CCA. Moreover, epithelial-mesenchymal transition (EMT)- and angiogenesis-associated miRNAs have been implicated in tumor cell dissemination and are able to determine clinical outcome. In fact, miRNAs involved in cell survival might even determine chemotherapy response. This review provides an overview of known miRNAs as CCA-specific biomarkers.","Source":"PubMed","category":"HUMAN","training_data":"miRNA profiling for diagnosis, prognosis and stratification of cancer treatment in cholangiocarcinoma Cholangiocarcinoma (CCA) is a lethal malignancy originating from the biliary tract epithelium. Most patients are diagnosed at an advanced stage. Even after resection with curative intent, prognosis remains poor. Previous studies have reported the evolving role of miRNAs as novel biomarkers in cancer diagnosis, prognostication and chemotherapy response. Various miRNAs, such as miR-21, miR-26, miR-122 and miR-150, have been identified as possible blood-based biomarkers for noninvasive diagnosis of CCA. Moreover, epithelial-mesenchymal transition (EMT)- and angiogenesis-associated miRNAs have been implicated in tumor cell dissemination and are able to determine clinical outcome. In fact, miRNAs involved in cell survival might even determine chemotherapy response. This review provides an overview of known miRNAs as CCA-specific biomarkers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"novel investigational therapies treating biliary tract carcinoma cholangiocarcinoma cca epithelial cell malignancy arising bile ducts peribiliary glands even though considered rare neoplasm incidence raising particularly developed countries prognosis generally poor patients present inclusion criteria surgery mainstay treatment tumour several genetic alterations potentially driving tumour progression described representing possible target new compounds areas covered clinical trial search clinicaltrials gov encompassing literature search pubmed asco esmo websites undertaken march 2016 expert opinion notwithstanding large number drug tested results still disappointing main reasons low number patients enrolled trials lack patient selection based biological profile tumours potential active drugs discharged simply beneficial particular subgroup patients un unselected population future direction research consider biomarker evaluation order describe genetic alteration drive tumour progression aggressiveness mechanisms drug resistance finally great interest consider results immunotherapy whenever available pubmed","probabilities":0.962963,"Title":"Novel investigational therapies for treating biliary tract carcinoma","Abstract":"Cholangiocarcinoma (CCA) is an epithelial cell malignancy arising from bile ducts and/or peribiliary glands. Even though it is considered as a rare neoplasm, its incidence is raising, particularly in developed countries. Prognosis is generally poor with few patients who present the inclusion criteria for surgery (the mainstay treatment for this tumour). Several genetic alterations potentially driving tumour progression have been described, representing a possible target for new compounds. Areas covered: A clinical trial search in Clinicaltrials.gov encompassing a literature search in PubMed and ASCO/ESMO Websites was undertaken in March 2016. Expert opinion: Notwithstanding a large number of drug tested, results are still disappointing. The main reasons could be the low number of patients enrolled in trials, and the lack of a patient selection based on the biological profile of the tumours. Potential active drugs could have been discharged simply because beneficial in a particular subgroup of patients and not in un unselected population. The future direction of the research should consider biomarker evaluation in order to describe the genetic alteration/s that drive tumour progression and aggressiveness and the mechanisms of drug resistance. Finally, it will be of great interest to consider the results of immunotherapy whenever available.","Source":"PubMed","category":"HUMAN","training_data":"Novel investigational therapies for treating biliary tract carcinoma Cholangiocarcinoma (CCA) is an epithelial cell malignancy arising from bile ducts and/or peribiliary glands. Even though it is considered as a rare neoplasm, its incidence is raising, particularly in developed countries. Prognosis is generally poor with few patients who present the inclusion criteria for surgery (the mainstay treatment for this tumour). Several genetic alterations potentially driving tumour progression have been described, representing a possible target for new compounds. Areas covered: A clinical trial search in Clinicaltrials.gov encompassing a literature search in PubMed and ASCO/ESMO Websites was undertaken in March 2016. Expert opinion: Notwithstanding a large number of drug tested, results are still disappointing. The main reasons could be the low number of patients enrolled in trials, and the lack of a patient selection based on the biological profile of the tumours. Potential active drugs could have been discharged simply because beneficial in a particular subgroup of patients and not in un unselected population. The future direction of the research should consider biomarker evaluation in order to describe the genetic alteration/s that drive tumour progression and aggressiveness and the mechanisms of drug resistance. Finally, it will be of great interest to consider the results of immunotherapy whenever available. PubMed","prediction_labels":"HUMAN"},{"cleaned":"improved overall survival intraductal papillary mucinous neoplasm bile duct analysis large national cancer registry abstract available google scholar","probabilities":0.9799733,"Title":"Improved Overall Survival With Intraductal Papillary Mucinous Neoplasm Of The Bile Duct: Analysis Of A Large National Cancer Registry","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Improved Overall Survival With Intraductal Papillary Mucinous Neoplasm Of The Bile Duct: Analysis Of A Large National Cancer Registry Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma stem like subset shapes tumor initiating niche educating associated macrophages background aims therapeutically challenging subset cells termed cancer stem cells cscs responsible cholangiocarcinoma cca clinical severity presence tumor associated macrophages tams prognostic significance cca malignancies thus hypothesized cscs may actively shape tumor supportive immune niche methods cca cells cultured 3d conditions generate spheres cca sphere analysis vivo tumorigenic engraftment immune deficient mice molecular characterization performed vitro vivo effect cca spheres macrophage precursors tested culturing healthy donor cluster differentiation cd 14 cca sphere conditioned medium results cca spheres engrafted 100 transplanted mice revealed significant 20 3 fold increase tumor initiating fraction p 0 0011 sustained tumorigenic potential diverse xenograft generations moreover cca spheres highly enriched csc liver cancer embryonic stem cell markers gene protein levels next fluorescence activated cell sorting analysis showed presence cca sphere conditioned medium cd14 macrophages expressed key markers cd68 cd115 human leukocyte antigen d related cd206 indicating cca sphere conditioned medium strong macrophage activator gene expression profile cca sphere activated macrophages revealed unique molecular tam like features confirmed high invasion capacity also freshly isolated macrophages cca resections recapitulated similar molecular phenotype vitro educated macrophages consistent invasive features largest cd163 set found tumor front human cca specimens n 23 correlated high level serum cancer antigen 19 9 n 17 among mediators released cca spheres interleukin il 13 il34 osteoactivin detected confirmed cca patient sera n 12 surprisingly significant association il13 il34 osteoactivin sphere stem like genes provided cca database n 104 vitro combination il13 il34 osteoactivin responsible macrophage differentiation invasion well vivo tumor promoting effect conclusion cca cscs molded specific subset stem like associated macrophages thus providing rationale synergistic therapeutic strategy cca disease lay summary immune plasticity represents important hallmark tumor outcome since cancer stem cells able manipulate stromal cells needs better definition key dysregulated immune subtypes responsible cooperating supporting tumor initiation may facilitate development new therapeutic approaches considering human cholangiocarcinoma represents clinical emergency essential move predictive models order understand adaptive process macrophage component imprinting polarization maintenance engaged tumor stem like compartment stn","probabilities":0.9467213,"Title":"Cholangiocarcinoma Stem-Like Subset Shapes Tumor-Initiating Niche By Educating Associated Macrophages","Abstract":"Background & aims: A therapeutically challenging subset of cells, termed cancer stem cells (CSCs) are responsible for cholangiocarcinoma (CCA) clinical severity. Presence of tumor-associated macrophages (TAMs) has prognostic significance in CCA and other malignancies. Thus, we hypothesized that CSCs may actively shape their tumor-supportive immune niche. \r\n\r\n Methods: CCA cells were cultured in 3D conditions to generate spheres. CCA sphere analysis of in vivo tumorigenic-engraftment in immune-deficient mice and molecular characterization was performed. The in vitro and in vivo effect of CCA spheres on macrophage precursors was tested after culturing healthy donor cluster of differentiation (CD)14+ with CCA-sphere conditioned medium. \r\n\r\n Results: CCA spheres engrafted in 100% of transplanted mice and revealed a significant 20.3-fold increase in tumor-initiating fraction (p=0.0011) and a sustained tumorigenic potential through diverse xenograft-generations. Moreover, CCA spheres were highly enriched for CSC, liver cancer and embryonic stem cell markers both at gene and protein levels. Next, fluorescence-activated cell sorting analysis showed that in the presence of CCA sphere conditioned medium, CD14+ macrophages expressed key markers (CD68, CD115, human leukocyte antigen-D related, CD206) indicating that CCA sphere conditioned medium was a strong macrophage-activator. Gene expression profile of CCA sphere activated macrophages revealed unique molecular TAM-like features confirmed by high invasion capacity. Also, freshly isolated macrophages from CCA resections recapitulated a similar molecular phenotype of in vitro-educated macrophages. Consistent with invasive features, the largest CD163+ set was found in the tumor front of human CCA specimens (n=23) and correlated with a high level of serum cancer antigen 19.9 (n=17). Among mediators released by CCA spheres, only interleukin (IL)13, IL34 and osteoactivin were detected and further confirmed in CCA patient sera (n=12). Surprisingly, a significant association of IL13, IL34 and osteoactivin with sphere stem-like genes was provided by a CCA database (n=104). In vitro combination of IL13, IL34, osteoactivin was responsible for macrophage-differentiation and invasion, as well as for in vivo tumor-promoting effect. \r\n\r\n Conclusion: CCA-CSCs molded a specific subset of stem-like associated macrophages thus providing a rationale for a synergistic therapeutic strategy for CCA-disease. \r\n\r\n Lay summary: Immune plasticity represents an important hallmark of tumor outcome. Since cancer stem cells are able to manipulate stromal cells to their needs, a better definition of the key dysregulated immune subtypes responsible for cooperating in supporting tumor initiation may facilitate the development of new therapeutic approaches. Considering that human cholangiocarcinoma represents a clinical emergency, it is essential to move to predictive models in order to understand the adaptive process of macrophage component (imprinting, polarization and maintenance) engaged by tumor stem-like compartment.","Source":"STN","category":"ANIMAL","training_data":"Cholangiocarcinoma Stem-Like Subset Shapes Tumor-Initiating Niche By Educating Associated Macrophages Background & aims: A therapeutically challenging subset of cells, termed cancer stem cells (CSCs) are responsible for cholangiocarcinoma (CCA) clinical severity. Presence of tumor-associated macrophages (TAMs) has prognostic significance in CCA and other malignancies. Thus, we hypothesized that CSCs may actively shape their tumor-supportive immune niche. \r\n\r\n Methods: CCA cells were cultured in 3D conditions to generate spheres. CCA sphere analysis of in vivo tumorigenic-engraftment in immune-deficient mice and molecular characterization was performed. The in vitro and in vivo effect of CCA spheres on macrophage precursors was tested after culturing healthy donor cluster of differentiation (CD)14+ with CCA-sphere conditioned medium. \r\n\r\n Results: CCA spheres engrafted in 100% of transplanted mice and revealed a significant 20.3-fold increase in tumor-initiating fraction (p=0.0011) and a sustained tumorigenic potential through diverse xenograft-generations. Moreover, CCA spheres were highly enriched for CSC, liver cancer and embryonic stem cell markers both at gene and protein levels. Next, fluorescence-activated cell sorting analysis showed that in the presence of CCA sphere conditioned medium, CD14+ macrophages expressed key markers (CD68, CD115, human leukocyte antigen-D related, CD206) indicating that CCA sphere conditioned medium was a strong macrophage-activator. Gene expression profile of CCA sphere activated macrophages revealed unique molecular TAM-like features confirmed by high invasion capacity. Also, freshly isolated macrophages from CCA resections recapitulated a similar molecular phenotype of in vitro-educated macrophages. Consistent with invasive features, the largest CD163+ set was found in the tumor front of human CCA specimens (n=23) and correlated with a high level of serum cancer antigen 19.9 (n=17). Among mediators released by CCA spheres, only interleukin (IL)13, IL34 and osteoactivin were detected and further confirmed in CCA patient sera (n=12). Surprisingly, a significant association of IL13, IL34 and osteoactivin with sphere stem-like genes was provided by a CCA database (n=104). In vitro combination of IL13, IL34, osteoactivin was responsible for macrophage-differentiation and invasion, as well as for in vivo tumor-promoting effect. \r\n\r\n Conclusion: CCA-CSCs molded a specific subset of stem-like associated macrophages thus providing a rationale for a synergistic therapeutic strategy for CCA-disease. \r\n\r\n Lay summary: Immune plasticity represents an important hallmark of tumor outcome. Since cancer stem cells are able to manipulate stromal cells to their needs, a better definition of the key dysregulated immune subtypes responsible for cooperating in supporting tumor initiation may facilitate the development of new therapeutic approaches. Considering that human cholangiocarcinoma represents a clinical emergency, it is essential to move to predictive models in order to understand the adaptive process of macrophage component (imprinting, polarization and maintenance) engaged by tumor stem-like compartment. STN","prediction_labels":"ANIMAL"},{"cleaned":"racial ethnic disparities national cohort ampullary cancer patients background objectives racial ethnic variations described different malignancies data exists ampullary cancer aim study present updated report epidemiology treatment patterns survival national cohort ampullary cancer patients methods patients diagnosed ampullary cancer 2004 2014 identified national cancer database overall survival estimated compared racial ethnic groups using log rank test results total 14 879 patients identified 78 patients white 9 hispanic 8 black 5 asian noted significant differences disease presentation socioeconomic status outcomes blacks lowest median overall survival 18 9 months followed whites 23 9 months hispanics 32 7 months asians 37 4 months multivariate cox proportional hazards model black associated worse survival compared white asian hispanic associated better survival conclusions overall survival ampullary cancer patients independently associated race ethnicity studies needed clarify whether disparities primarily due socioeconomic status biologic factors pubmed","probabilities":0.9799733,"Title":"Racial and ethnic disparities in a national cohort of ampullary cancer patients","Abstract":"BACKGROUND AND OBJECTIVES: Racial and ethnic variations have been described in the different malignancies, but no such data exists for ampullary cancer. The aim of this study was to present an updated report on the epidemiology, treatment patterns, and survival of a national cohort of ampullary cancer patients. METHODS: Patients diagnosed with ampullary cancer between 2004 and 2014 were identified in the National Cancer Database. Overall survival was estimated and compared between racial/ethnic groups using the log-rank test. RESULTS: A total of 14 879 patients were identified; 78% of the patients were White, 9% Hispanic, 8% Black, and 5% Asian. We noted significant differences in disease presentation, socioeconomic status, and outcomes. Blacks had the lowest median overall survival at 18.9 months followed by Whites at 23.9 months, Hispanics at 32.7 months, and Asians at 37.4 months. On a multivariate Cox proportional-hazards model, being Black was associated with worse survival compared to being White while being Asian and Hispanic were associated with better survival. CONCLUSIONS: Overall survival of ampullary cancer patients was independently associated with race and ethnicity. Further studies are needed to clarify whether these disparities are primarily due to socioeconomic status or biologic factors.","Source":"PubMed","category":"HUMAN","training_data":"Racial and ethnic disparities in a national cohort of ampullary cancer patients BACKGROUND AND OBJECTIVES: Racial and ethnic variations have been described in the different malignancies, but no such data exists for ampullary cancer. The aim of this study was to present an updated report on the epidemiology, treatment patterns, and survival of a national cohort of ampullary cancer patients. METHODS: Patients diagnosed with ampullary cancer between 2004 and 2014 were identified in the National Cancer Database. Overall survival was estimated and compared between racial/ethnic groups using the log-rank test. RESULTS: A total of 14 879 patients were identified; 78% of the patients were White, 9% Hispanic, 8% Black, and 5% Asian. We noted significant differences in disease presentation, socioeconomic status, and outcomes. Blacks had the lowest median overall survival at 18.9 months followed by Whites at 23.9 months, Hispanics at 32.7 months, and Asians at 37.4 months. On a multivariate Cox proportional-hazards model, being Black was associated with worse survival compared to being White while being Asian and Hispanic were associated with better survival. CONCLUSIONS: Overall survival of ampullary cancer patients was independently associated with race and ethnicity. Further studies are needed to clarify whether these disparities are primarily due to socioeconomic status or biologic factors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"aldh1a3 major aldehyde dehydrogenase isoform human cholangiocarcinoma cells affects prognosis gemcitabine resistance cholangiocarcinoma patients purpose intrahepatic cholangiocarcinoma fatal primary liver cancer resulting diagnosis advanced stage understanding mechanisms drug resistance metastasis cholangiocarcinoma may improve disease prognosis enhanced aldehyde dehydrogenase aldh activity suggested associated increased drug resistance metastasis study aims investigate roles aldh isoforms cholangiocarcinoma experimental design aldefluor assays rt pcr western blot analysis used identify major aldh isoforms contributing aldefluor activity human cholangiocarcinoma cell lines manipulated isoform expression hucct1 cells elucidate role aldh1a3 malignant progression cells finally used immunohistochemical staining evaluate clinical significance aldh1a3 77 hepatectomized cholangiocarcinoma patients additional 31 patients advanced cholangiocarcinoma received gemcitabine based therapy results aldh high cholangiocarcinoma cells migrated faster resistant gemcitabine among 19 aldh isoforms studied aldh1a3 found main contributor aldefluor activity addition also found knockdown aldh1a3 expression hucct1 cells markedly reduced sensitivity gemcitabine might attributed decreased expression ribonucleotide reductase m1 also migration importantly enzyme also identified independent poor prognostic factor patients intrahepatic cholangiocarcinoma well prognostic biomarker gemcitabine treated patients conclusions aldh1a3 plays important role enhancing malignant behavior cholangiocarcinoma serves new therapeutic target clin cancer res 22 16 4225 35 2016 aacr stn","probabilities":0.9467213,"Title":"Aldh1A3 The Major Aldehyde Dehydrogenase Isoform In Human Cholangiocarcinoma Cells Affects Prognosis And Gemcitabine Resistance In Cholangiocarcinoma Patients","Abstract":"Purpose: Intrahepatic cholangiocarcinoma is a fatal primary liver cancer resulting from diagnosis at an advanced stage. Understanding the mechanisms of drug resistance and metastasis of cholangiocarcinoma may improve the disease prognosis. Enhanced aldehyde dehydrogenase (ALDH) activity is suggested to be associated with increased drug resistance and the metastasis. This study aims to investigate the roles of the ALDH isoforms in cholangiocarcinoma. \r\n\r\n Experimental design: Aldefluor assays, RT-PCR, and Western blot analysis were used to identify the major ALDH isoforms contributing to Aldefluor activity in human cholangiocarcinoma cell lines. We manipulated isoform expression in HuCCT1 cells to elucidate the role of ALDH1A3 in the malignant progression of these cells. Finally, we used immunohistochemical staining to evaluate the clinical significance of ALDH1A3 in 77 hepatectomized cholangiocarcinoma patients and an additional 31 patients with advanced cholangiocarcinoma who received gemcitabine-based therapy. \r\n\r\n Results: ALDH(high) cholangiocarcinoma cells not only migrated faster but were more resistant to gemcitabine. Among the 19 ALDH isoforms studied, ALDH1A3 was found to be the main contributor to Aldefluor activity. In addition, we also found that knockdown of ALDH1A3 expression in HuCCT1 cells markedly reduced not only their sensitivity to gemcitabine, which might be attributed to a decreased expression of ribonucleotide reductase M1, but also their migration. Most importantly, this enzyme was also identified as an independent poor prognostic factor for patients with intrahepatic cholangiocarcinoma, as well as a prognostic biomarker of gemcitabine-treated patients. \r\n\r\n Conclusions: ALDH1A3 plays an important role in enhancing malignant behavior of cholangiocarcinoma and serves as a new therapeutic target. Clin Cancer Res; 22(16); 4225-35. ©2016 AACR.","Source":"STN","category":"ANIMAL","training_data":"Aldh1A3 The Major Aldehyde Dehydrogenase Isoform In Human Cholangiocarcinoma Cells Affects Prognosis And Gemcitabine Resistance In Cholangiocarcinoma Patients Purpose: Intrahepatic cholangiocarcinoma is a fatal primary liver cancer resulting from diagnosis at an advanced stage. Understanding the mechanisms of drug resistance and metastasis of cholangiocarcinoma may improve the disease prognosis. Enhanced aldehyde dehydrogenase (ALDH) activity is suggested to be associated with increased drug resistance and the metastasis. This study aims to investigate the roles of the ALDH isoforms in cholangiocarcinoma. \r\n\r\n Experimental design: Aldefluor assays, RT-PCR, and Western blot analysis were used to identify the major ALDH isoforms contributing to Aldefluor activity in human cholangiocarcinoma cell lines. We manipulated isoform expression in HuCCT1 cells to elucidate the role of ALDH1A3 in the malignant progression of these cells. Finally, we used immunohistochemical staining to evaluate the clinical significance of ALDH1A3 in 77 hepatectomized cholangiocarcinoma patients and an additional 31 patients with advanced cholangiocarcinoma who received gemcitabine-based therapy. \r\n\r\n Results: ALDH(high) cholangiocarcinoma cells not only migrated faster but were more resistant to gemcitabine. Among the 19 ALDH isoforms studied, ALDH1A3 was found to be the main contributor to Aldefluor activity. In addition, we also found that knockdown of ALDH1A3 expression in HuCCT1 cells markedly reduced not only their sensitivity to gemcitabine, which might be attributed to a decreased expression of ribonucleotide reductase M1, but also their migration. Most importantly, this enzyme was also identified as an independent poor prognostic factor for patients with intrahepatic cholangiocarcinoma, as well as a prognostic biomarker of gemcitabine-treated patients. \r\n\r\n Conclusions: ALDH1A3 plays an important role in enhancing malignant behavior of cholangiocarcinoma and serves as a new therapeutic target. Clin Cancer Res; 22(16); 4225-35. ©2016 AACR. STN","prediction_labels":"ANIMAL"},{"cleaned":"liver resection intrahepatic cholangiocarcinoma ajcc stage evaluation survival benefit prognostic accuracy current ajcc staging system n m classification intrahepatic cholangiocarcinoma icc usually confirmed advanced stage time diagnosis surgical exploration however indication surgical treatment usually controversial icc advanced stages retrospective study aims evaluate clinical value surgery tumors order identify appropriate patients benefit surgery evaluate prognostic accuracy current staging system advanced icc january 2007 december 2011 387 consecutive surgically treated patients icc ajcc stage evaluated survival compared among different patients grouped different elements ajcc staging system prognostic importance extent lymph node ln metastasis relative ajcc n m classification system assessed data showed survival much better patients ajcc stage group median survival time mst 9 0 months ajcc stage b group mst 5 0 months p 0 001 ajcc stage b group survival patients anytn2 3m0 subgroup mst 9 0 months much better anytn0m1 subgroup mst 3 0 months better anytn2 3m1 subgroup mst 4 0 months p 0 001 overall r0 r1 liver resection indicated patients ajcc stage group anytn2 3m0 subgroup ajcc stage b group patients groups benefit surgery relatively better survival staging advanced icc n2 3 instead m1 extended ln metastasis classification superior comparison ajcc staging system pubmed","probabilities":0.9799733,"Title":"Liver resection for intrahepatic cholangiocarcinoma in AJCC‑stage Ⅳ: An evaluation of the survival benefit and prognostic accuracy of current AJCC staging system on N and M classification","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is usually confirmed in advanced stage at the time of diagnosis or after surgical exploration, however, indication of surgical treatment is usually controversial for ICC in advanced stages. This retrospective study aims to evaluate clinical value of surgery for such tumors, in order to identify the appropriate patients who will benefit from surgery, and to evaluate the prognostic accuracy of the current staging system for advanced ICC. From January 2007 to December 2011, 387 consecutive surgically treated patients with ICC in AJCC‑stage Ⅳ were evaluated. Survival was compared among different patients grouped by different elements of AJCC staging system. The prognostic importance of extent of lymph node (LN) metastasis relative to the AJCC N and M classification system was assessed. Our data showed that survival was much better for patients in AJCC‑stage ⅣA group (median survival time, MST, 9.0 months) than in AJCC‑stage ⅣB group (MST, 5.0 months) (P<0.001). While in AJCC‑stage ⅣB group, survival for patients in AnyTN2‑3M0 subgroup (MST, 9.0 months) was much better than in AnyTN0M1 subgroup (MST, 3.0 months); and better than in AnyTN2‑3M1 subgroup (MST, 4.0 months) (P<0.001). Overall, R0 and R1 liver resection should be indicated for patients in AJCC‑stage ⅣA group and AnyTN2‑3M0 subgroup in AJCC‑stage ⅣB group, as patients in these groups will benefit from surgery with relatively better survival. Staging of advanced ICC by N2‑3 instead of M1 for extended LN metastasis classification is superior in comparison with the AJCC staging system.","Source":"PubMed","category":"HUMAN","training_data":"Liver resection for intrahepatic cholangiocarcinoma in AJCC‑stage Ⅳ: An evaluation of the survival benefit and prognostic accuracy of current AJCC staging system on N and M classification Intrahepatic cholangiocarcinoma (ICC) is usually confirmed in advanced stage at the time of diagnosis or after surgical exploration, however, indication of surgical treatment is usually controversial for ICC in advanced stages. This retrospective study aims to evaluate clinical value of surgery for such tumors, in order to identify the appropriate patients who will benefit from surgery, and to evaluate the prognostic accuracy of the current staging system for advanced ICC. From January 2007 to December 2011, 387 consecutive surgically treated patients with ICC in AJCC‑stage Ⅳ were evaluated. Survival was compared among different patients grouped by different elements of AJCC staging system. The prognostic importance of extent of lymph node (LN) metastasis relative to the AJCC N and M classification system was assessed. Our data showed that survival was much better for patients in AJCC‑stage ⅣA group (median survival time, MST, 9.0 months) than in AJCC‑stage ⅣB group (MST, 5.0 months) (P<0.001). While in AJCC‑stage ⅣB group, survival for patients in AnyTN2‑3M0 subgroup (MST, 9.0 months) was much better than in AnyTN0M1 subgroup (MST, 3.0 months); and better than in AnyTN2‑3M1 subgroup (MST, 4.0 months) (P<0.001). Overall, R0 and R1 liver resection should be indicated for patients in AJCC‑stage ⅣA group and AnyTN2‑3M0 subgroup in AJCC‑stage ⅣB group, as patients in these groups will benefit from surgery with relatively better survival. Staging of advanced ICC by N2‑3 instead of M1 for extended LN metastasis classification is superior in comparison with the AJCC staging system. PubMed","prediction_labels":"HUMAN"},{"cleaned":"smoking alcohol consumption risk extrahepatic cholangiocarcinoma meta analysis aim assess association smoking alcohol consumption extrahepatic cholangiocarcinoma ecc meta analysis clinical observational studies methods literature search conducted using embase medline databases inception 31 may 2013 without language limitations manually searching references retrieved articles case control cohort studies investigated association smoking alcohol consumption ecc included quality studies assessed using newcastle ottawa quality assessment scale summary relative risks corresponding 95 ci calculated using random effects model publication bias assessed begg funnel plot egger test results total 12 eligible articles 11 case control studies one cohort study included meta analysis eleven studies reported association smoking ecc pooled analysis indicated smokers increased risk ecc development compared non smokers summary rr 1 23 95 ci 1 01 1 50 correlation present population based studies n 5 summary rr 1 47 95 ci 1 06 2 05 hospital based studies n 6 summary rr 1 10 95 ci 0 88 1 37 non asian regions n 7 summary rr 1 39 95 ci 1 03 1 87 asia n 4 summary rr 1 08 95 ci 0 85 1 38 seven studies reported association consuming alcohol ecc pooled analysis indicated alcohol drinkers similar risk ecc development individuals drink alcohol summary rr 1 09 95 ci 0 87 1 37 moderate heterogeneity among studies evidence publication bias conclusion smoking associated increased risk ecc alcohol consumption population based studies particularly cohort studies warranted enable definitive conclusions pubmed","probabilities":0.9799733,"Title":"Smoking, alcohol consumption, and the risk of extrahepatic cholangiocarcinoma: a meta-analysis","Abstract":"AIM: To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma (ECC) through a meta-analysis of clinical observational studies. METHODS: A literature search was conducted using Embase and MEDLINE databases from inception to 31 May 2013 without language limitations, and by manually searching the references of retrieved articles. Case-control and cohort studies that investigated the association between smoking or alcohol consumption and ECC were included. The quality of these studies was assessed using the Newcastle-Ottawa quality assessment scale. Summary relative risks and corresponding 95%CI were calculated using a random-effects model. Publication bias was assessed by Begg's funnel plot and Egger's test. RESULTS: A total of 12 eligible articles (11 case-control studies and one cohort study) were included in this meta-analysis. Eleven studies reported the association between smoking and ECC. Pooled analysis indicated that smokers had an increased risk of ECC development as compared with non-smokers (summary RR = 1.23; 95%CI: 1.01-1.50). This correlation was present in population-based studies (n = 5; summary RR = 1.47; 95%CI: 1.06-2.05) but not in hospital-based studies (n = 6; summary RR = 1.10; 95%CI: 0.88-1.37) and in non-Asian regions (n = 7; summary RR = 1.39; 95%CI: 1.03-1.87) but not in Asia (n = 4; summary RR = 1.08; 95%CI: 0.85-1.38). Seven studies reported an association between consuming alcohol and ECC. Pooled analysis indicated that alcohol drinkers had a similar risk of ECC development as did individuals who did not drink alcohol (summary RR = 1.09; 95%CI: 0.87-1.37). There was moderate heterogeneity among the studies and no evidence of publication bias. CONCLUSION: Smoking is associated with an increased risk of ECC, but alcohol consumption is not. Further population-based studies, particularly cohort studies, are warranted to enable definitive conclusions.","Source":"PubMed","category":"HUMAN","training_data":"Smoking, alcohol consumption, and the risk of extrahepatic cholangiocarcinoma: a meta-analysis AIM: To assess the association between smoking and alcohol consumption and extrahepatic cholangiocarcinoma (ECC) through a meta-analysis of clinical observational studies. METHODS: A literature search was conducted using Embase and MEDLINE databases from inception to 31 May 2013 without language limitations, and by manually searching the references of retrieved articles. Case-control and cohort studies that investigated the association between smoking or alcohol consumption and ECC were included. The quality of these studies was assessed using the Newcastle-Ottawa quality assessment scale. Summary relative risks and corresponding 95%CI were calculated using a random-effects model. Publication bias was assessed by Begg's funnel plot and Egger's test. RESULTS: A total of 12 eligible articles (11 case-control studies and one cohort study) were included in this meta-analysis. Eleven studies reported the association between smoking and ECC. Pooled analysis indicated that smokers had an increased risk of ECC development as compared with non-smokers (summary RR = 1.23; 95%CI: 1.01-1.50). This correlation was present in population-based studies (n = 5; summary RR = 1.47; 95%CI: 1.06-2.05) but not in hospital-based studies (n = 6; summary RR = 1.10; 95%CI: 0.88-1.37) and in non-Asian regions (n = 7; summary RR = 1.39; 95%CI: 1.03-1.87) but not in Asia (n = 4; summary RR = 1.08; 95%CI: 0.85-1.38). Seven studies reported an association between consuming alcohol and ECC. Pooled analysis indicated that alcohol drinkers had a similar risk of ECC development as did individuals who did not drink alcohol (summary RR = 1.09; 95%CI: 0.87-1.37). There was moderate heterogeneity among the studies and no evidence of publication bias. CONCLUSION: Smoking is associated with an increased risk of ECC, but alcohol consumption is not. Further population-based studies, particularly cohort studies, are warranted to enable definitive conclusions. PubMed","prediction_labels":"HUMAN"},{"cleaned":"biliary intervention beyond drainage intraductal photodynamic therapy klatskin tumor patients purpose percutaneous transhepatic biliary drainage ptbd gold standard palliation non surgical klatskin tumor patients impact additional intraductal photodynamic therapy pdt patient survival quality life object presentation material methods ninety three pdt procedures one ten per patient performed 30 biopsy confirmed klatskin tumor patients 12 females 18 males age range 34 75 years previous ptbd since february 2008 patients bismuth iv type tumors surgical candidates second generation chlorin sensitizers 0 6 2 0 mg kg administrated intravenously 2 4 hours prior procedure consecutive wire guided insertion optical fiber intraductal laser irradiation 662 nm laser lahta milon low fluence rate pulse mode regimens 12 50 mw cm2 1000 j per liver follow included clinical examination lab tests abdomen mri every 3 months results post procedural mortality patient developed post procedural liver abscess required percutaneous biliary drainage intraductal pdt resulted bile duct recanalization cholangitis abatement improvement liver function tests several mri findings post pdt peritumoral inflammatory infiltration lymph node reaction etc assumed possible immune system activation median survival rate 1 2 year survival rates first pdt procedure diagnosis 13 2 months range 2 47 months 65 7 23 5 27 6 months range 5 68 months 81 8 54 5 respectively conclusion intraductal pdt safe effective strategy non surgical klatskin tumor patient management increasing survival rate quality life google scholar","probabilities":0.9799733,"Title":"Biliary Intervention Beyond The Drainage: Intraductal Photodynamic Therapy In Klatskin Tumor Patients","Abstract":"Purpose: Percutaneous transhepatic biliary drainage (PTBD) is a\n“gold standard for palliation” in non-surgical Klatskin tumor patients.\nImpact of additional intraductal photodynamic therapy (PDT) on\npatient survival and quality of life is an object of this presentation.\nMaterial and Methods: Ninety-three PDT procedures (from one\nto ten per patient) have been performed in 30 biopsy-confirmed\nKlatskin tumor patients (12 females, 18 males; age range 34-75 years)\nwith previous PTBD since February 2008. All patients had Bismuth\nIV type tumors and were not surgical candidates. The second generation\nchlorin sensitizers, 0.6-2.0 mg/kg, were administrated intravenously\n2-4 hours prior the procedure with consecutive wire-guided\ninsertion of optical fiber and intraductal laser irradiation (662-nm\nlaser LAHTA-MILON) at low fluence rate pulse mode regimens (12-\n50 mW/cm2, up to 1000 J per liver). The follow-up included clinical\nexamination, lab tests, and abdomen MRI every 3 months.\nResults: There was no post-procedural mortality. The only patient\nwho developed post-procedural liver abscess required percutaneous\nbiliary drainage. Intraductal PDT resulted in bile duct recanalization,\ncholangitis abatement, and improvement of liver function\ntests. Several MRI findings (post-PDT peritumoral inflammatory infiltration,\nlymph node reaction, etc.) assumed possible immune system\nactivation. The median survival rate and 1- and 2-year survival\nrates from the first PDT procedure and from the diagnosis were 13.2\nmonths (range 2-47 months), 65.7%, and 23.5% and 27.6 months\n(range 5-68 months), 81.8%, and 54.5%, respectively.\nConclusion: The intraductal PDT is a safe and an effective strategy\nin non-surgical Klatskin tumor patient management, increasing\nboth survival rate and quality of life.","Source":"Google Scholar","category":"HUMAN","training_data":"Biliary Intervention Beyond The Drainage: Intraductal Photodynamic Therapy In Klatskin Tumor Patients Purpose: Percutaneous transhepatic biliary drainage (PTBD) is a\n“gold standard for palliation” in non-surgical Klatskin tumor patients.\nImpact of additional intraductal photodynamic therapy (PDT) on\npatient survival and quality of life is an object of this presentation.\nMaterial and Methods: Ninety-three PDT procedures (from one\nto ten per patient) have been performed in 30 biopsy-confirmed\nKlatskin tumor patients (12 females, 18 males; age range 34-75 years)\nwith previous PTBD since February 2008. All patients had Bismuth\nIV type tumors and were not surgical candidates. The second generation\nchlorin sensitizers, 0.6-2.0 mg/kg, were administrated intravenously\n2-4 hours prior the procedure with consecutive wire-guided\ninsertion of optical fiber and intraductal laser irradiation (662-nm\nlaser LAHTA-MILON) at low fluence rate pulse mode regimens (12-\n50 mW/cm2, up to 1000 J per liver). The follow-up included clinical\nexamination, lab tests, and abdomen MRI every 3 months.\nResults: There was no post-procedural mortality. The only patient\nwho developed post-procedural liver abscess required percutaneous\nbiliary drainage. Intraductal PDT resulted in bile duct recanalization,\ncholangitis abatement, and improvement of liver function\ntests. Several MRI findings (post-PDT peritumoral inflammatory infiltration,\nlymph node reaction, etc.) assumed possible immune system\nactivation. The median survival rate and 1- and 2-year survival\nrates from the first PDT procedure and from the diagnosis were 13.2\nmonths (range 2-47 months), 65.7%, and 23.5% and 27.6 months\n(range 5-68 months), 81.8%, and 54.5%, respectively.\nConclusion: The intraductal PDT is a safe and an effective strategy\nin non-surgical Klatskin tumor patient management, increasing\nboth survival rate and quality of life. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"high expression matrix metalloproteinase 9 indicates poor prognosis human hilar cholangiocarcinoma high expression matrix metalloproteinase 9 mmp 9 found correlated tumor progression poor prognosis variety carcinomas however studies investigated role mmp 9 human hilar cholangiocarcinoma study total 58 patients hilar cholangiocarcinoma underwent curative resection included study expression mmp 9 analyzed immunohistochemistry using streptavidin peroxidase complex method correlation mmp 9 overexpression clinicopathological features survival time patients investigated results showed mmp 9 overexpression prominent cancer cells mainly localized cytoplasm mmp 9 overexpression observed 46 5 tumors showed correlation clinicopathological parameters patients high mmp 9 expression significantly poorer overall survival rate negative low mmp 9 expression p 0 038 multivariate analysis confirmed mmp 9 overexpression independent prognostic factor p 0 007 conclusion overexpression mmp 9 valuable independent prognostic indicator hilar cholangiocarcinoma pubmed","probabilities":0.8684211,"Title":"High expression of matrix metalloproteinase-9 indicates poor prognosis in human hilar cholangiocarcinoma","Abstract":"High expression of matrix metalloproteinase-9 (MMP-9) was found to be correlated with tumor progression and poor prognosis in a variety of carcinomas. However, few studies have investigated the role of MMP-9 in human hilar cholangiocarcinoma. In this study, a total of 58 patients with hilar cholangiocarcinoma who underwent curative resection were included in this study. The expression of MMP-9 was analyzed by immunohistochemistry using the streptavidin peroxidase complex method. The correlation of MMP-9 overexpression with clinicopathological features and survival time of patients was investigated. The results showed that MMP-9 overexpression was prominent in cancer cells and mainly localized in the cytoplasm. MMP-9 overexpression was observed in 46.5% tumors, which showed no correlation with clinicopathological parameters. Patients with high MMP-9 expression had a significantly poorer overall survival rate than those with negative or low MMP-9 expression (P = 0.038). Multivariate analysis confirmed that MMP-9 overexpression was an independent prognostic factor (P = 0.007). In conclusion, overexpression of MMP-9 is a valuable independent prognostic indicator in hilar cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"High expression of matrix metalloproteinase-9 indicates poor prognosis in human hilar cholangiocarcinoma High expression of matrix metalloproteinase-9 (MMP-9) was found to be correlated with tumor progression and poor prognosis in a variety of carcinomas. However, few studies have investigated the role of MMP-9 in human hilar cholangiocarcinoma. In this study, a total of 58 patients with hilar cholangiocarcinoma who underwent curative resection were included in this study. The expression of MMP-9 was analyzed by immunohistochemistry using the streptavidin peroxidase complex method. The correlation of MMP-9 overexpression with clinicopathological features and survival time of patients was investigated. The results showed that MMP-9 overexpression was prominent in cancer cells and mainly localized in the cytoplasm. MMP-9 overexpression was observed in 46.5% tumors, which showed no correlation with clinicopathological parameters. Patients with high MMP-9 expression had a significantly poorer overall survival rate than those with negative or low MMP-9 expression (P = 0.038). Multivariate analysis confirmed that MMP-9 overexpression was an independent prognostic factor (P = 0.007). In conclusion, overexpression of MMP-9 is a valuable independent prognostic indicator in hilar cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"modified response evaluation criteria solid tumors european association study liver criteria using delayed phase imaging early time point predict survival patients unresectable intrahepatic cholangiocarcinoma following yttrium 90 radioembolization purpose investigate early imaging prognostic factors unresectable intrahepatic cholangiocarcinoma icc refractory standard chemotherapy yttrium 90 90 y radioembolization therapy materials methods institutional review board approved prospective correlative study 21 consecutive patients icc refractory standard chemotherapy underwent 90 y radioembolization therapy target overall response evaluation criteria solid tumors recist modified recist mrecist european association study liver easl treatment responses assessed mrecist easl criteria modified application delayed phases dynamic contrast enhanced cross sectional imaging studies conventional definitions complete partial response applied responses comprised objective response restaging imaging obtained 1 3 month intervals patient death survival analyses kaplan meier log rank proportional models including application landmark method avoid lead time bias performed day treatment significance set p 05 results median overall survival os time 90 y therapy 16 3 months 95 confidence interval 7 2 25 4 mo significant differences mrecist easl versus recist found categorizing patients responders nonresponders p 001 significantly prolonged os observed patients targeted objective response based modified mrecist easl criteria p 005 p 001 respectively 3 months recist found correlate survival 1 3 month follow conclusions modified target mrecist easl criteria employ delayed phase contrast enhancement 3 months 90 y radioembolization therapy icc predicted os recist correlate survival pubmed","probabilities":0.9799733,"Title":"Modified response evaluation criteria in solid tumors and European Association for The Study of the Liver criteria using delayed-phase imaging at an early time point predict survival in patients with unresectable intrahepatic cholangiocarcinoma following yttrium-90 radioembolization","Abstract":"PURPOSE: To investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) refractory to standard chemotherapy after yttrium-90 ((90)Y) radioembolization therapy. MATERIALS AND METHODS: In an institutional review board-approved prospective correlative study, 21 consecutive patients with ICC refractory to standard chemotherapy underwent (90)Y radioembolization therapy. Target and overall Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) treatment responses were assessed. The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies. Conventional definitions for complete and partial response were applied; these responses comprised objective response. Restaging imaging was obtained at 1- and 3-month intervals until patient death. Survival analyses by Kaplan-Meier and log-rank proportional models including application of the landmark method to avoid lead-time bias were performed from the day of treatment. Significance was set at P < .05. RESULTS: Median overall survival (OS) from the time of (90)Y therapy was 16.3 months (95% confidence interval, 7.2-25.4 mo). Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders (P < .001). Significantly prolonged OS was observed for patients with targeted objective response based on modified mRECIST and EASL criteria (P = .005 and P = .001, respectively) at 3 months. RECIST was not found to correlate with survival at 1- or 3-month follow-up. CONCLUSIONS: Modified target mRECIST and EASL criteria that employ delayed-phase contrast enhancement at 3 months after (90)Y radioembolization therapy for ICC predicted OS. RECIST did not correlate with survival.","Source":"PubMed","category":"HUMAN","training_data":"Modified response evaluation criteria in solid tumors and European Association for The Study of the Liver criteria using delayed-phase imaging at an early time point predict survival in patients with unresectable intrahepatic cholangiocarcinoma following yttrium-90 radioembolization PURPOSE: To investigate early imaging prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) refractory to standard chemotherapy after yttrium-90 ((90)Y) radioembolization therapy. MATERIALS AND METHODS: In an institutional review board-approved prospective correlative study, 21 consecutive patients with ICC refractory to standard chemotherapy underwent (90)Y radioembolization therapy. Target and overall Response Evaluation Criteria In Solid Tumors (RECIST), modified RECIST (mRECIST), and European Association for the Study of the Liver (EASL) treatment responses were assessed. The mRECIST and EASL criteria were modified for application on delayed phases of dynamic contrast-enhanced cross-sectional imaging studies. Conventional definitions for complete and partial response were applied; these responses comprised objective response. Restaging imaging was obtained at 1- and 3-month intervals until patient death. Survival analyses by Kaplan-Meier and log-rank proportional models including application of the landmark method to avoid lead-time bias were performed from the day of treatment. Significance was set at P < .05. RESULTS: Median overall survival (OS) from the time of (90)Y therapy was 16.3 months (95% confidence interval, 7.2-25.4 mo). Significant differences between mRECIST and EASL versus RECIST were found when categorizing patients into responders and nonresponders (P < .001). Significantly prolonged OS was observed for patients with targeted objective response based on modified mRECIST and EASL criteria (P = .005 and P = .001, respectively) at 3 months. RECIST was not found to correlate with survival at 1- or 3-month follow-up. CONCLUSIONS: Modified target mRECIST and EASL criteria that employ delayed-phase contrast enhancement at 3 months after (90)Y radioembolization therapy for ICC predicted OS. RECIST did not correlate with survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"eukaryotic translation initiation factor 6 overexpression plays major role translational control gallbladder cancer background gallbladder cancer gbc rare neoplasia biliary tract high mortality rates poor prognosis signs symptoms gbc specific often arise late stage disease reason diagnosis typically made cancer already advanced stages prognosis survival less 5 years 90 cases biomarkers monitor disease progression novel therapeutic alternative targets tumors strongly required commonly dysregulated protein synthesis contributes carcinogenesis cancer progression case protein synthesis directs translation specific mrnas turn promotes cell survival invasion angiogenesis metastasis tumors eukaryotes protein synthesis regulated initiation rate limiting step involving eukaryotic translation initiation factors eifs hypothesize eifs represent crossroads development gbc might serve potential biomarkers study focus role eif6 anti association factor ribosomal subunits gbc methods human gbc samples expression eif6 analyzed biochemically protein immunohistochemistry immunoblot analyses mrna levels qrt pcr results high levels eif6 correlated shorter overall survival biliary tract cancer btc patients n 28 immunohistochemical data tissue microarrays n 114 demonstrated significantly higher expression levels eif6 gbc compared non neoplastic tissue higher eif6 expression protein immunoblot mrna qrt pcr level confirmed analyzing fresh frozen gbc patient samples n 14 depletion eif6 using specific sirna mediated knockdown mz cha 2 tfk 1 cell lines inhibited cell proliferation induced apoptosis conclusion data indicates eif6 overexpression plays major role translational control gbc indicates potential new biomarker therapeutic target gbc pubmed","probabilities":1.0,"Title":"Eukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer","Abstract":"BACKGROUND: Gallbladder cancer (GBC) is a rare neoplasia of the biliary tract with high mortality rates and poor prognosis. Signs and symptoms of GBC are not specific and often arise at late stage of disease. For this reason, diagnosis is typically made when the cancer is already in advanced stages, and prognosis for survival is less than 5 years in 90% of cases. Biomarkers to monitor disease progression and novel therapeutic alternative targets for these tumors are strongly required. Commonly, dysregulated protein synthesis contributes to carcinogenesis and cancer progression. In this case, protein synthesis directs translation of specific mRNAs, and, in turn, promotes cell survival, invasion, angiogenesis, and metastasis of tumors. In eukaryotes, protein synthesis is regulated at its initiation, which is a rate-limiting step involving eukaryotic translation initiation factors (eIFs). We hypothesize that eIFs represent crossroads in the development of GBC, and might serve as potential biomarkers. The study focus was the role of eIF6 (an anti-association factor for the ribosomal subunits) in GBC. METHODS: In human GBC samples, the expression of eIF6 was analyzed biochemically at the protein (immunohistochemistry, immunoblot analyses) and mRNA levels (qRT-PCR). RESULTS: High levels of eIF6 correlated with shorter overall survival in biliary tract cancer (BTC) patients (n = 28). Immunohistochemical data from tissue microarrays (n = 114) demonstrated significantly higher expression levels of eIF6 in GBC compared to non-neoplastic tissue. Higher eIF6 expression on protein (immunoblot) and mRNA (qRT-PCR) level was confirmed by analyzing fresh frozen GBC patient samples (n = 14). Depletion of eIF6 (using specific siRNA-mediated knockdown) in Mz-ChA-2 and TFK-1 cell lines inhibited cell proliferation and induced apoptosis. CONCLUSION: Our data indicates that eIF6 overexpression plays a major role in the translational control of GBC, and indicates its potential as a new biomarker and therapeutic target in GBC.","Source":"PubMed","category":"HUMAN","training_data":"Eukaryotic translation initiation factor 6 overexpression plays a major role in the translational control of gallbladder cancer BACKGROUND: Gallbladder cancer (GBC) is a rare neoplasia of the biliary tract with high mortality rates and poor prognosis. Signs and symptoms of GBC are not specific and often arise at late stage of disease. For this reason, diagnosis is typically made when the cancer is already in advanced stages, and prognosis for survival is less than 5 years in 90% of cases. Biomarkers to monitor disease progression and novel therapeutic alternative targets for these tumors are strongly required. Commonly, dysregulated protein synthesis contributes to carcinogenesis and cancer progression. In this case, protein synthesis directs translation of specific mRNAs, and, in turn, promotes cell survival, invasion, angiogenesis, and metastasis of tumors. In eukaryotes, protein synthesis is regulated at its initiation, which is a rate-limiting step involving eukaryotic translation initiation factors (eIFs). We hypothesize that eIFs represent crossroads in the development of GBC, and might serve as potential biomarkers. The study focus was the role of eIF6 (an anti-association factor for the ribosomal subunits) in GBC. METHODS: In human GBC samples, the expression of eIF6 was analyzed biochemically at the protein (immunohistochemistry, immunoblot analyses) and mRNA levels (qRT-PCR). RESULTS: High levels of eIF6 correlated with shorter overall survival in biliary tract cancer (BTC) patients (n = 28). Immunohistochemical data from tissue microarrays (n = 114) demonstrated significantly higher expression levels of eIF6 in GBC compared to non-neoplastic tissue. Higher eIF6 expression on protein (immunoblot) and mRNA (qRT-PCR) level was confirmed by analyzing fresh frozen GBC patient samples (n = 14). Depletion of eIF6 (using specific siRNA-mediated knockdown) in Mz-ChA-2 and TFK-1 cell lines inhibited cell proliferation and induced apoptosis. CONCLUSION: Our data indicates that eIF6 overexpression plays a major role in the translational control of GBC, and indicates its potential as a new biomarker and therapeutic target in GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognosis clinicopathologic features patients advanced stage isocitrate dehydrogenase idh mutant idh wild type intrahepatic cholangiocarcinoma background conflicting data exist regarding prognostic impact isocitrate dehydrogenase idh mutation intrahepatic cholangiocarcinoma icc limited data exist patients advanced stage disease similarly clinical phenotype patients advanced idh mutant idhm icc characterized study report correlation idh mutation status prognosis clinicopathologic features patients advanced icc methods patients histologically confirmed advanced icc underwent tumor mutational profiling routine part care 2009 2014 evaluated clinical pathological data collected retrospective chart review patients idhm versus idh wild type idhwt icc pretreatment tumor volume calculated computed tomography magnetic resonance imaging results 104 patients icc evaluated 30 28 8 idh mutation 25 0 idh1 3 8 idh2 median overall survival differ significantly idhm idhwt patients 15 0 vs 20 1 months respectively p 17 pretreatment serum carbohydrate antigen 19 9 ca19 9 level idhm idhwt patients 34 5 118 0 u ml respectively p 04 age diagnosis sex histologic grade pattern metastasis differ significantly idh mutation status conclusion idh mutation associated prognosis patients advanced icc clinical phenotypes advanced idhm idhwt icc similar patients idhm icc lower median serum ca19 9 level presentation implications practice previous studies assessing prognostic impact isocitrate dehydrogenase idh gene mutation intrahepatic cholangiocarcinoma icc mainly focused patients early stage disease undergone resection studies offer conflicting results target population clinical trials idh inhibitors patients unresectable metastatic disease current study first focus prognosis clinical phenotype population reports largest cohort patients advanced idh mutant icc date finding idh mutation lacks prognostic significance advanced icc preliminary needs confirmed prospectively larger study pubmed","probabilities":0.9799733,"Title":"Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC. METHODS: Patients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging. RESULTS: Of the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status. CONCLUSION: The IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation. IMPLICATIONS FOR PRACTICE: Previous studies assessing the prognostic impact of the isocitrate dehydrogenase (IDH) gene mutation in intrahepatic cholangiocarcinoma (ICC) mainly focused on patients with early-stage disease who have undergone resection. These studies offer conflicting results. The target population for clinical trials of IDH inhibitors is patients with unresectable or metastatic disease, and the current study is the first to focus on the prognosis and clinical phenotype of this population and reports on the largest cohort of patients with advanced IDH mutant ICC to date. The finding that the IDH mutation lacks prognostic significance in advanced ICC is preliminary and needs to be confirmed prospectively in a larger study.","Source":"PubMed","category":"HUMAN","training_data":"Prognosis and Clinicopathologic Features of Patients With Advanced Stage Isocitrate Dehydrogenase (IDH) Mutant and IDH Wild-Type Intrahepatic Cholangiocarcinoma BACKGROUND: Conflicting data exist regarding the prognostic impact of the isocitrate dehydrogenase (IDH) mutation in intrahepatic cholangiocarcinoma (ICC), and limited data exist in patients with advanced-stage disease. Similarly, the clinical phenotype of patients with advanced IDH mutant (IDHm) ICC has not been characterized. In this study, we report the correlation of IDH mutation status with prognosis and clinicopathologic features in patients with advanced ICC. METHODS: Patients with histologically confirmed advanced ICC who underwent tumor mutational profiling as a routine part of their care between 2009 and 2014 were evaluated. Clinical and pathological data were collected by retrospective chart review for patients with IDHm versus IDH wild-type (IDHwt) ICC. Pretreatment tumor volume was calculated on computed tomography or magnetic resonance imaging. RESULTS: Of the 104 patients with ICC who were evaluated, 30 (28.8%) had an IDH mutation (25.0% IDH1, 3.8% IDH2). The median overall survival did not differ significantly between IDHm and IDHwt patients (15.0 vs. 20.1 months, respectively; p = .17). The pretreatment serum carbohydrate antigen 19-9 (CA19-9) level in IDHm and IDHwt patients was 34.5 and 118.0 U/mL, respectively (p = .04). Age at diagnosis, sex, histologic grade, and pattern of metastasis did not differ significantly by IDH mutation status. CONCLUSION: The IDH mutation was not associated with prognosis in patients with advanced ICC. The clinical phenotypes of advanced IDHm and IDHwt ICC were similar, but patients with IDHm ICC had a lower median serum CA19-9 level at presentation. IMPLICATIONS FOR PRACTICE: Previous studies assessing the prognostic impact of the isocitrate dehydrogenase (IDH) gene mutation in intrahepatic cholangiocarcinoma (ICC) mainly focused on patients with early-stage disease who have undergone resection. These studies offer conflicting results. The target population for clinical trials of IDH inhibitors is patients with unresectable or metastatic disease, and the current study is the first to focus on the prognosis and clinical phenotype of this population and reports on the largest cohort of patients with advanced IDH mutant ICC to date. The finding that the IDH mutation lacks prognostic significance in advanced ICC is preliminary and needs to be confirmed prospectively in a larger study. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical resection hilar cholangiocarcinoma experience improves resectability objectives hilar cholangiocarcinoma resection provides opportunity longterm survival us experience hilar cholangiocarcinoma examined determine effect clinical experience negative margin r0 resection rates methods conducted retrospective analysis 110 consecutive hilar cholangiocarcinoma patients presenting 18 year period analyses performed using chi squared wilcoxon rank sum kaplan meier methods multivariable cox logistic regression modelling results 110 patients cohort 59 1 male 90 9 white median patient age 64 years total 59 53 6 patients underwent resection 37 demonstrated r0 30 day mortality rate 5 1 complication rate 39 0 rate resectability increased time 36 4 vs 70 9 p 0 001 percentage r0 resections 10 9 vs 56 5 p 0 001 59 patients underwent resection 23 39 0 experienced recurrence multivariable cox regression analysis identified resection margins hazard ratio hr 4 124 positive vs negative p 0 002 type operation hr 5 075 exploration vs resection p 0 001 significant survival conclusions although r0 resection achieved minority patients patients reasonable chance longterm survival last decade seen significant rise rates resectability klatskin tumour specialty centres pubmed","probabilities":0.9799733,"Title":"Surgical resection for hilar cholangiocarcinoma: experience improves resectability","Abstract":"OBJECTIVES:   In hilar cholangiocarcinoma, resection provides the only opportunity for longterm survival. A US experience of hilar cholangiocarcinoma was examined to determine the effect of clinical experience on negative margin (R0) resection rates. METHODS:   We conducted a retrospective analysis of 110 consecutive hilar cholangiocarcinoma patients presenting over an 18-year period. Analyses were performed using chi-squared, Wilcoxon rank sum and Kaplan-Meier methods, and multivariable Cox and logistic regression modelling. RESULTS:   Of the 110 patients in the cohort, 59.1% were male and 90.9% were White. The median patient age was 64 years. A total of 59 (53.6%) patients underwent resection; 37 of these demonstrated R0. The 30-day mortality rate was 5.1%; the complication rate was 39.0%. The rate of resectability increased over time (36.4% vs. 70.9%; P= 0.001), as did the percentage of R0 resections (10.9% vs. 56.5%; P < 0.001). Of the 59 patients who underwent resection, 23 (39.0%) experienced recurrence. Multivariable Cox regression analysis identified resection margins [hazard ratio (HR) = 4.124 for positive vs. negative; P= 0.002] and type of operation (HR = 5.075 for exploration vs. resection; P= 0.001) as significant to survival. CONCLUSIONS:   Although R0 resection can be achieved in only a minority of patients, these patients have a reasonable chance of longterm survival. The last decade has seen a significant rise in rates of resectability of Klatskin's tumour at specialty centres.","Source":"PubMed","category":"HUMAN","training_data":"Surgical resection for hilar cholangiocarcinoma: experience improves resectability OBJECTIVES:   In hilar cholangiocarcinoma, resection provides the only opportunity for longterm survival. A US experience of hilar cholangiocarcinoma was examined to determine the effect of clinical experience on negative margin (R0) resection rates. METHODS:   We conducted a retrospective analysis of 110 consecutive hilar cholangiocarcinoma patients presenting over an 18-year period. Analyses were performed using chi-squared, Wilcoxon rank sum and Kaplan-Meier methods, and multivariable Cox and logistic regression modelling. RESULTS:   Of the 110 patients in the cohort, 59.1% were male and 90.9% were White. The median patient age was 64 years. A total of 59 (53.6%) patients underwent resection; 37 of these demonstrated R0. The 30-day mortality rate was 5.1%; the complication rate was 39.0%. The rate of resectability increased over time (36.4% vs. 70.9%; P= 0.001), as did the percentage of R0 resections (10.9% vs. 56.5%; P < 0.001). Of the 59 patients who underwent resection, 23 (39.0%) experienced recurrence. Multivariable Cox regression analysis identified resection margins [hazard ratio (HR) = 4.124 for positive vs. negative; P= 0.002] and type of operation (HR = 5.075 for exploration vs. resection; P= 0.001) as significant to survival. CONCLUSIONS:   Although R0 resection can be achieved in only a minority of patients, these patients have a reasonable chance of longterm survival. The last decade has seen a significant rise in rates of resectability of Klatskin's tumour at specialty centres. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term survival analysis liver transplantation hepatocellular carcinoma bile duct tumor thrombus background long term prognosis liver transplantation lt hepatocellular carcinoma hcc macroscopic bile duct tumor thrombus bdtt well assessed study intended analyze post transplantation outcomes patients hcc macroscopic bdtt methods retrospective study performed 14 patients underwent lt hcc bdtt 0 7 selection institutional database 2052 adult lt cases results types lt living donor lt 13 deceased donor lt 1 extents bdtt ueda type 1 4 type 2 3 type 3 7 milan criteria met 8 57 1 concurrent bile duct resection performed 7 50 mean model end stage liver disease score 18 7 4 9 mean graft recipient weight ratio 1 2 0 3 one case perioperative mortality one case hcc unrelated late mortality cumulative hcc recurrence rates 15 4 1 year 46 2 3 years 46 2 5 years overall patient survival rates 92 9 1 year 57 1 3 years 50 5 years univariate risk factor analyses revealed macrovascular invasion significant risk factor hcc recurrence p 019 conclusions results study revealed lt hcc macroscopic bdtt high risk post transplantation hcc recurrence therefore large volume studies necessary elucidate risk factors google scholar","probabilities":0.9799733,"Title":"Long-Term Survival Analysis Of Liver Transplantation For Hepatocellular Carcinoma With Bile Duct Tumor Thrombus","Abstract":"Background\nLong-term prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) has not been well assessed. This study intended to analyze the post-transplantation outcomes in patients who had HCC with macroscopic BDTT.\nMethods\nA retrospective study was performed with 14 patients who underwent LT for HCC with BDTT (0.7%) after selection from an institutional database of 2052 adult LT cases.\nResults\nTypes of LT were living donor LT in 13 and deceased donor LT in 1. The extents of BDTT were Ueda type 1 in 4, type 2 in 3, and type 3 in 7. Milan criteria were met in 8 (57.1%). Concurrent bile duct resection was performed in 7 (50%). Mean model for end-stage liver disease score was 18.7 ± 4.9. Mean graft-recipient weight ratio was 1.2 ± 0.3. There was one case of perioperative mortality and one case of HCC-unrelated late mortality. Cumulative HCC recurrence rates were 15.4% at 1 year, 46.2% at 3 years, and 46.2% at 5 years. Overall patient survival rates were 92.9% at 1 year, 57.1% at 3 years, and 50% at 5 years. Univariate risk factor analyses revealed that only macrovascular invasion was a significant risk factor for HCC recurrence (P = .019).\nConclusions\nThe results of this study revealed that LT for HCC with macroscopic BDTT has a high risk of post-transplantation HCC recurrence; therefore, further large-volume studies are necessary to elucidate the risk factors.","Source":"Google Scholar","category":"HUMAN","training_data":"Long-Term Survival Analysis Of Liver Transplantation For Hepatocellular Carcinoma With Bile Duct Tumor Thrombus Background\nLong-term prognosis of liver transplantation (LT) for hepatocellular carcinoma (HCC) with macroscopic bile duct tumor thrombus (BDTT) has not been well assessed. This study intended to analyze the post-transplantation outcomes in patients who had HCC with macroscopic BDTT.\nMethods\nA retrospective study was performed with 14 patients who underwent LT for HCC with BDTT (0.7%) after selection from an institutional database of 2052 adult LT cases.\nResults\nTypes of LT were living donor LT in 13 and deceased donor LT in 1. The extents of BDTT were Ueda type 1 in 4, type 2 in 3, and type 3 in 7. Milan criteria were met in 8 (57.1%). Concurrent bile duct resection was performed in 7 (50%). Mean model for end-stage liver disease score was 18.7 ± 4.9. Mean graft-recipient weight ratio was 1.2 ± 0.3. There was one case of perioperative mortality and one case of HCC-unrelated late mortality. Cumulative HCC recurrence rates were 15.4% at 1 year, 46.2% at 3 years, and 46.2% at 5 years. Overall patient survival rates were 92.9% at 1 year, 57.1% at 3 years, and 50% at 5 years. Univariate risk factor analyses revealed that only macrovascular invasion was a significant risk factor for HCC recurrence (P = .019).\nConclusions\nThe results of this study revealed that LT for HCC with macroscopic BDTT has a high risk of post-transplantation HCC recurrence; therefore, further large-volume studies are necessary to elucidate the risk factors. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"dose escalation radiotherapy unresectable extrahepatic cholangiocarcinoma purpose evaluate effect escalated dose radiation therapy edr defined doses 50 4 gy 28 fractions 59 5 gy bed overall survival os freedom local progression fflp freedom distant progression ffdp patients unresectable extrahepatic cholangiocarcinoma ehcc methods consecutive cohort 80 patients underwent radiotherapy unresectable ehcc 2001 2015 identified demographic tumor treatment toxicity laboratory variables collected maximal rt doses ranged 30 75 gy median 50 4 gy 1 8 4 5 gy fraction gross tumor volume gtv coverage maximal dose edr group ranged 38 100 kaplan meier method used estimate os fflp ffdp univariate multivariate cox regression models analyzed results radiotherapy median os fflp ffdp 18 7 22 6 24 3 months respectively significant difference os fflp patients received edr portions gtv patients multivariate analysis bigger gtv age ecog performance status independently associated shorter os local progression chemotherapy prior rt independently associated shorter fflp high baseline neutrophil lymphocyte ratio 5 3 independently associated shorter ffdp toxicity grades similar edr lower doses except lymphopenia higher edr p 0 053 conclusions edr selective portions gtv may benefit patients unresectable ehcc despite acceptable toxicity new methods improve local control survival unresectable ehcc needed pubmed","probabilities":0.9799733,"Title":"Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma","Abstract":"PURPOSE: To evaluate the effect of escalated dose radiation therapy (EDR, defined as doses >50.4 Gy in 28 fractions [59.5 Gy BED]) on overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) of patients with unresectable extrahepatic cholangiocarcinoma (EHCC). METHODS: A consecutive cohort of 80 patients who underwent radiotherapy for unresectable EHCC from 2001 to 2015 was identified. Demographic, tumor, treatment, toxicity, and laboratory variables were collected. The maximal RT doses ranged from 30 to 75 Gy (median 50.4 Gy, at 1.8-4.5 Gy/fraction). Gross tumor volume (GTV) coverage by maximal dose in EDR group ranged from 38% to 100%. Kaplan-Meier method was used to estimate OS, FFLP, and FFDP. Univariate and multivariate Cox regression models were analyzed. RESULTS: After radiotherapy, median OS, FFLP, and FFDP were 18.7, 22.6, and 24.3 months, respectively. There was no significant difference in OS or FFLP between patients who received EDR to portions of the GTV and patients who did not. On multivariate analysis, bigger GTV, age, and ECOG performance status were independently associated with shorter OS. Local progression on chemotherapy prior to RT was independently associated with shorter FFLP. High baseline neutrophil/lymphocyte ratio (>5.3) was independently associated with shorter FFDP. Toxicity grades were similar in EDR and lower doses except lymphopenia which was higher in EDR (P = 0.053). CONCLUSIONS: EDR to selective portions of the GTV may not benefit patients with unresectable EHCC despite having acceptable toxicity. New methods to improve local control and survival for unresectable EHCC are needed.","Source":"PubMed","category":"HUMAN","training_data":"Dose escalation of radiotherapy in unresectable extrahepatic cholangiocarcinoma PURPOSE: To evaluate the effect of escalated dose radiation therapy (EDR, defined as doses >50.4 Gy in 28 fractions [59.5 Gy BED]) on overall survival (OS), freedom from local progression (FFLP), and freedom from distant progression (FFDP) of patients with unresectable extrahepatic cholangiocarcinoma (EHCC). METHODS: A consecutive cohort of 80 patients who underwent radiotherapy for unresectable EHCC from 2001 to 2015 was identified. Demographic, tumor, treatment, toxicity, and laboratory variables were collected. The maximal RT doses ranged from 30 to 75 Gy (median 50.4 Gy, at 1.8-4.5 Gy/fraction). Gross tumor volume (GTV) coverage by maximal dose in EDR group ranged from 38% to 100%. Kaplan-Meier method was used to estimate OS, FFLP, and FFDP. Univariate and multivariate Cox regression models were analyzed. RESULTS: After radiotherapy, median OS, FFLP, and FFDP were 18.7, 22.6, and 24.3 months, respectively. There was no significant difference in OS or FFLP between patients who received EDR to portions of the GTV and patients who did not. On multivariate analysis, bigger GTV, age, and ECOG performance status were independently associated with shorter OS. Local progression on chemotherapy prior to RT was independently associated with shorter FFLP. High baseline neutrophil/lymphocyte ratio (>5.3) was independently associated with shorter FFDP. Toxicity grades were similar in EDR and lower doses except lymphopenia which was higher in EDR (P = 0.053). CONCLUSIONS: EDR to selective portions of the GTV may not benefit patients with unresectable EHCC despite having acceptable toxicity. New methods to improve local control and survival for unresectable EHCC are needed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma clinicopathological differences peripheral type hilar type background intrahepatic cholangiocarcinoma icc categorized peripheral icc picc hilar icc hicc aims study clarify clinicopathological differences picc hicc determine useful prognostic factors patients icc following aggressive surgical resection methods medical records 44 patients icc underwent surgical resection retrospectively reviewed clinicopathological factors compared patients picc hicc univariate multivariate models used analyze effect clinicopathological factors disease specific survival results disease specific survival rates 44 patients 76 1 year 60 3 years 47 5 years clinicopathological factors differ patients picc hicc except preoperative jaundice p 0 001 preoperative biliary drainage p 0 001 postoperative complication p 0 046 macroscopic type p 0 001 multivariate analysis revealed lymph node status independent prognostic factor disease specific survival 5 year disease specific survival rates patients without nodal involvement 23 66 respectively p 0 004 conclusions clinicopathological characteristics almost similar patients picc hicc nodal involvement potent prognostic factor patients icc pubmed","probabilities":0.9799733,"Title":"Intrahepatic cholangiocarcinoma: clinicopathological differences between peripheral type and hilar type","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is categorized as peripheral ICC (PICC) or hilar ICC (HICC). The aims of this study are to clarify clinicopathological differences between PICC and HICC and to determine useful prognostic factors for patients with ICC following aggressive surgical resection. METHODS: Medical records of 44 patients with ICC who underwent surgical resection were retrospectively reviewed. Clinicopathological factors were compared between patients with PICC and HICC. Univariate and multivariate models were used to analyze the effect of clinicopathological factors on disease-specific survival. RESULTS: Disease-specific survival rates for the 44 patients were 76% at 1 year, 60% at 3 years, and 47% at 5 years. Clinicopathological factors did not differ between patients with PICC and HICC except preoperative jaundice (P<0.001), preoperative biliary drainage (P=0.001), postoperative complication (P=0.046), and macroscopic type (P<0.001). Multivariate analysis revealed that only lymph node status was an independent prognostic factor of disease-specific survival. The 5-year disease-specific survival rates of patients with or without nodal involvement were 23% and 66%, respectively (P=0.004). CONCLUSIONS: Clinicopathological characteristics are almost similar between patients with PICC and HICC. Nodal involvement is a potent prognostic factor for patients with ICC.","Source":"PubMed","category":"HUMAN","training_data":"Intrahepatic cholangiocarcinoma: clinicopathological differences between peripheral type and hilar type BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is categorized as peripheral ICC (PICC) or hilar ICC (HICC). The aims of this study are to clarify clinicopathological differences between PICC and HICC and to determine useful prognostic factors for patients with ICC following aggressive surgical resection. METHODS: Medical records of 44 patients with ICC who underwent surgical resection were retrospectively reviewed. Clinicopathological factors were compared between patients with PICC and HICC. Univariate and multivariate models were used to analyze the effect of clinicopathological factors on disease-specific survival. RESULTS: Disease-specific survival rates for the 44 patients were 76% at 1 year, 60% at 3 years, and 47% at 5 years. Clinicopathological factors did not differ between patients with PICC and HICC except preoperative jaundice (P<0.001), preoperative biliary drainage (P=0.001), postoperative complication (P=0.046), and macroscopic type (P<0.001). Multivariate analysis revealed that only lymph node status was an independent prognostic factor of disease-specific survival. The 5-year disease-specific survival rates of patients with or without nodal involvement were 23% and 66%, respectively (P=0.004). CONCLUSIONS: Clinicopathological characteristics are almost similar between patients with PICC and HICC. Nodal involvement is a potent prognostic factor for patients with ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiology characteristics patients hepatocellular carcinoma care united states background incidence liver intrahepatic bile duct cancer hepatocellular carcinoma hcc accounts 72 7 dou bled 1992 2014 united states us objectives non interventional cross sectional study aimed examine latest epidemiology hcc analyzing 2 large us databases methods ibm marketscan ibm ms surveillance epidemiol ogy end results national program cancer registries seer npcr databases analyzed separately patients age 18 years hcc primary cancer covered employer pro vided commercial medicare supplemental insurance identified ibm ms database using international classification dis eases ninth tenth revision icd 9 10 codes index diagnosis defined first eligible hcc diagnosis within study period jan 2012 sep 2017 hcc diagnosis prior 12 months comorbidities performance status distribution patients treatments received described seer npcr jan 2010 dec 2014 nationally representative patient sample analyzed describe incidence mortality patients hcc results total 8150 119 927 patients identified ibm ms seer npcr respectively patients predominately male databases ibm ms 72 seer npcr 75 hcc inci dence rates among ibm ms cohort 5 9 5 5 4 9 4 7 per 100 000 person years 2013 2014 2015 2016 respectively downward trend hcc incidence rate post 2013 pop ulation coincided drop hcc incidence rate 2013 2014 seer npcr among ibm ms cohort 6 36 59 patients hepatitis b hepatitis c cirrhosis index diagnosis respectively patients 88 considered good perfor mance status defined without hospice hospital bed oxygen use etc index diagnosis embolization chemo targeted therapies common treatments received patients irrespective disease stage 31 12 respectively patients metastatic hcc 19 18 respectively approximately 44 index hcc diagnosis occurred hospital outpatient settings 31 inpatient settings 23 physician offices conclusions study identified recent epidemiologic changes patients hcc characterized comorbidities commer cially insured us representative population epidemiologic data may important considerations us payers making coverage policies patients hcc google scholar","probabilities":0.9799733,"Title":"Epidemiology And Characteristics Of Patients With Hepatocellular Carcinoma And Care In The United States","Abstract":"Background: The incidence of liver and intrahepatic bile duct cancer,\nof which hepatocellular carcinoma (HCC) accounts for 72.7%, has dou-\nbled from 1992 to 2014 in the United States (US).\nObjectives: This non‐interventional, cross‐sectional study aimed to\nexamine the latest epidemiology of HCC by analyzing 2 large US\ndatabases\nMethods: The IBM MarketScan (IBM‐MS) and Surveillance, Epidemiol-\nogy, and End Results‐National Program of Cancer Registries (SEER‐\nNPCR) databases were analyzed separately. Patients (age ≥ 18 years)\nwith HCC as the primary cancer who were covered by employer‐pro-\nvided commercial or Medicare supplemental insurance were identified\nfrom the IBM‐MS database using International Classification of Dis-\neases, Ninth and Tenth Revision (ICD‐9/10) codes. Index diagnosis was defined as the first eligible HCC diagnosis within the study period\n(Jan 2012‐Sep 2017) and no other HCC diagnosis in the prior\n12 months. Comorbidities, performance status, distribution of\npatients, and treatments received were described. In SEER‐NPCR\n(Jan 2010 ‐Dec 2014), a nationally representative patient sample was\nanalyzed to describe the incidence and mortality of patients with HCC.\nResults: A total of 8150 and 119,927 patients were identified in IBM‐\nMS and SEER‐NPCR, respectively. Patients were predominately male\nin both databases (IBM‐MS: 72%; SEER‐NPCR: 75%). The HCC inci-\ndence rates among the IBM‐MS cohort were 5.9, 5.5, 4.9, and 4.7 per\n100,000 person‐years in 2013, 2014, 2015, and 2016, respectively.\nThe downward trend in the HCC incidence rate post‐2013 for this pop-\nulation coincided with the drop in HCC incidence rate from 2013 to\n2014 in SEER‐NPCR. Among the IBM‐MS cohort, 6%, 36%, and 59%\nof patients had hepatitis B, hepatitis C, and cirrhosis at index diagnosis,\nrespectively. Most patients (88%) were considered to have good perfor-\nmance status (defined as without any hospice, hospital bed, oxygen use,\netc.) at index diagnosis. Embolization and chemo/targeted therapies\nwere the most common treatments received by patients irrespective\nof the disease stage (31% and 12%, respectively) and in patients with\nmetastatic HCC (19% and 18%, respectively). Approximately 44% of\nthe index HCC diagnosis occurred in hospital outpatient settings, 31%\nin inpatient settings, and 23% in physician offices.\nConclusions: This study identified the recent epidemiologic changes in\npatients with HCC and characterized their comorbidities in a commer-\ncially insured and a US representative population. These epidemiologic\ndata may be important considerations for US payers making coverage\npolicies for patients with HCC","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology And Characteristics Of Patients With Hepatocellular Carcinoma And Care In The United States Background: The incidence of liver and intrahepatic bile duct cancer,\nof which hepatocellular carcinoma (HCC) accounts for 72.7%, has dou-\nbled from 1992 to 2014 in the United States (US).\nObjectives: This non‐interventional, cross‐sectional study aimed to\nexamine the latest epidemiology of HCC by analyzing 2 large US\ndatabases\nMethods: The IBM MarketScan (IBM‐MS) and Surveillance, Epidemiol-\nogy, and End Results‐National Program of Cancer Registries (SEER‐\nNPCR) databases were analyzed separately. Patients (age ≥ 18 years)\nwith HCC as the primary cancer who were covered by employer‐pro-\nvided commercial or Medicare supplemental insurance were identified\nfrom the IBM‐MS database using International Classification of Dis-\neases, Ninth and Tenth Revision (ICD‐9/10) codes. Index diagnosis was defined as the first eligible HCC diagnosis within the study period\n(Jan 2012‐Sep 2017) and no other HCC diagnosis in the prior\n12 months. Comorbidities, performance status, distribution of\npatients, and treatments received were described. In SEER‐NPCR\n(Jan 2010 ‐Dec 2014), a nationally representative patient sample was\nanalyzed to describe the incidence and mortality of patients with HCC.\nResults: A total of 8150 and 119,927 patients were identified in IBM‐\nMS and SEER‐NPCR, respectively. Patients were predominately male\nin both databases (IBM‐MS: 72%; SEER‐NPCR: 75%). The HCC inci-\ndence rates among the IBM‐MS cohort were 5.9, 5.5, 4.9, and 4.7 per\n100,000 person‐years in 2013, 2014, 2015, and 2016, respectively.\nThe downward trend in the HCC incidence rate post‐2013 for this pop-\nulation coincided with the drop in HCC incidence rate from 2013 to\n2014 in SEER‐NPCR. Among the IBM‐MS cohort, 6%, 36%, and 59%\nof patients had hepatitis B, hepatitis C, and cirrhosis at index diagnosis,\nrespectively. Most patients (88%) were considered to have good perfor-\nmance status (defined as without any hospice, hospital bed, oxygen use,\netc.) at index diagnosis. Embolization and chemo/targeted therapies\nwere the most common treatments received by patients irrespective\nof the disease stage (31% and 12%, respectively) and in patients with\nmetastatic HCC (19% and 18%, respectively). Approximately 44% of\nthe index HCC diagnosis occurred in hospital outpatient settings, 31%\nin inpatient settings, and 23% in physician offices.\nConclusions: This study identified the recent epidemiologic changes in\npatients with HCC and characterized their comorbidities in a commer-\ncially insured and a US representative population. These epidemiologic\ndata may be important considerations for US payers making coverage\npolicies for patients with HCC Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"diagnostic prognostic serum marker cholangiocarcinoma review cholangiocarcinoma cca fatal disease typically diagnosed late treated ineffectively morbidity mortality rates cca rise markedly patietns cca currently poor prognosis however possible diagnose cca early effective treat methods available cca patients achieve better quality life therefore preventing process cca early stages urgent problem solve accurate quick safe method diagnose early stage cca required present review discusses risk factors status research certain serum markers cca sensitivity specificity markers differ explore accurate serum markers may novel direction method diagnosis cca laboratory medicine future google scholar","probabilities":0.9799733,"Title":"Diagnostic And Prognostic Serum Marker Of Cholangiocarcinoma (Review)","Abstract":"Cholangiocarcinoma (CCA) is a fatal disease that is typically diagnosed late and treated ineffectively. As the morbidity and mortality rates for CCA rise markedly, patietns with CCA currently have a poor prognosis. However, if it were possible to diagnose CCA early while effective treat methods are available, CCA patients would achieve a better quality of life. Therefore, preventing the process of CCA in the early stages is an urgent problem to solve. An accurate, quick and safe method to diagnose early‑stage CCA is required. The present review discusses the risk factors, status of research and certain serum markers of CCA. The sensitivity and specificity of these markers differ from each other. To explore the more accurate serum markers may be a novel direction and method for the diagnosis of CCA in laboratory medicine in the future.","Source":"Google Scholar","category":"HUMAN","training_data":"Diagnostic And Prognostic Serum Marker Of Cholangiocarcinoma (Review) Cholangiocarcinoma (CCA) is a fatal disease that is typically diagnosed late and treated ineffectively. As the morbidity and mortality rates for CCA rise markedly, patietns with CCA currently have a poor prognosis. However, if it were possible to diagnose CCA early while effective treat methods are available, CCA patients would achieve a better quality of life. Therefore, preventing the process of CCA in the early stages is an urgent problem to solve. An accurate, quick and safe method to diagnose early‑stage CCA is required. The present review discusses the risk factors, status of research and certain serum markers of CCA. The sensitivity and specificity of these markers differ from each other. To explore the more accurate serum markers may be a novel direction and method for the diagnosis of CCA in laboratory medicine in the future. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"ampullary cancer twenty year series single centre abstract available google scholar","probabilities":0.9799733,"Title":"Ampullary Cancer: Twenty Year-Series In A Single Centre","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Ampullary Cancer: Twenty Year-Series In A Single Centre Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"expression long non coding rna anril predicts poor prognosis intrahepatic cholangiocarcinoma background intrahepatic cholangiocarcinoma icca deadly cancer worldwide associated increased incidence limited therapeutic options absence reliable prognostic biomarkers long non coding rnas lncrna emerge relevant biomarkers cancer associated tumor progression however lncrna poorly investigated icca aim identify lncrna significantly associated survival patients icca tumor resection curative intent methods gene expression profiling q rt pcr performed cohort 39 clinically well annotated icca univariate cox proportional hazards model wald statistic used identify lncrna significantly associated overall os disease free dfs survival results signature made 9 lncrna identified significantly p 0 05 associated os dfs including 4 lncrna lnc cdk9 1 xloc_l2_009441 cdkn2b as1 hoxc13 highly expressed poor prognosis icca 5 lncrna lnc cchcr1 1 lnc af131215 3 1 lnc cblb 5 col18a1 as2 lnc rell2 1 highly expressed better prognosis icca validated cdkn2b as1 anril poor prognosis biomarker icca also hepatocellular carcinoma kidney renal clear cell carcinoma uterine corpus endometrial carcinoma conclusions report prognosis lncrna signature icca clinical relevance cdkn2b as1 anril overexpression several cancers pubmed","probabilities":0.962963,"Title":"Expression of long non-coding RNA ANRIL predicts a poor prognosis in intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide associated with an increased incidence, limited therapeutic options and absence of reliable prognostic biomarkers. Long non-coding RNAs (lncRNA) emerge as relevant biomarkers in cancer being associated with tumor progression. However, lncRNA have been poorly investigated in iCCA. AIM: To identify lncRNA significantly associated with the survival of patients with iCCA after tumor resection for curative intent. METHODS: Gene expression profiling and Q-RT-PCR were performed from a cohort of 39 clinically well-annotated iCCA. Univariate Cox proportional hazards model with Wald Statistic was used to identify lncRNA significantly associated with overall (OS) and/or disease-free (DFS) survival. RESULTS: A signature made of 9 lncRNA was identified to be significantly (P < 0.05) associated with OS and DFS, including 4 lncRNA (lnc-CDK9-1, XLOC_l2_009441, CDKN2B-AS1, HOXC13-AS) highly expressed in poor prognosis iCCA and 5 lncRNA (lnc-CCHCR1-1, lnc-AF131215.3.1, lnc-CBLB-5, COL18A1-AS2, lnc-RELL2-1) highly expressed in better prognosis iCCA. We further validated CDKN2B-AS1 (ANRIL) as a poor prognosis biomarker, not only in iCCA, but also in hepatocellular carcinoma, kidney renal clear cell carcinoma and uterine corpus endometrial carcinoma. CONCLUSIONS: We report a prognosis lncRNA signature in iCCA and the clinical relevance of CDKN2B-AS1 (ANRIL) overexpression in several cancers.","Source":"PubMed","category":"HUMAN","training_data":"Expression of long non-coding RNA ANRIL predicts a poor prognosis in intrahepatic cholangiocarcinoma BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide associated with an increased incidence, limited therapeutic options and absence of reliable prognostic biomarkers. Long non-coding RNAs (lncRNA) emerge as relevant biomarkers in cancer being associated with tumor progression. However, lncRNA have been poorly investigated in iCCA. AIM: To identify lncRNA significantly associated with the survival of patients with iCCA after tumor resection for curative intent. METHODS: Gene expression profiling and Q-RT-PCR were performed from a cohort of 39 clinically well-annotated iCCA. Univariate Cox proportional hazards model with Wald Statistic was used to identify lncRNA significantly associated with overall (OS) and/or disease-free (DFS) survival. RESULTS: A signature made of 9 lncRNA was identified to be significantly (P < 0.05) associated with OS and DFS, including 4 lncRNA (lnc-CDK9-1, XLOC_l2_009441, CDKN2B-AS1, HOXC13-AS) highly expressed in poor prognosis iCCA and 5 lncRNA (lnc-CCHCR1-1, lnc-AF131215.3.1, lnc-CBLB-5, COL18A1-AS2, lnc-RELL2-1) highly expressed in better prognosis iCCA. We further validated CDKN2B-AS1 (ANRIL) as a poor prognosis biomarker, not only in iCCA, but also in hepatocellular carcinoma, kidney renal clear cell carcinoma and uterine corpus endometrial carcinoma. CONCLUSIONS: We report a prognosis lncRNA signature in iCCA and the clinical relevance of CDKN2B-AS1 (ANRIL) overexpression in several cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"asbestos ingestion gastrointestinal cancer possible underestimated hazard presence asbestos fibres afs drinking water linked gastrointestinal cancers however regulated several countries due conflicting evidence areas covered reports mainly associated af ingestion gastric colorectal cancer experimental evidence suggested role timing extent exposure showed ingested afs induce toxic effects stomach ileum colon histological alterations negative effects molecular level cross placenta enter foetal organs including liver seem able act co carcinogen agent occupational studies suggest associations asbestos exposure intrahepatic cholangiocarcinoma observations exist indicating possibility afs enter liver bile enteric absorption expert commentary risk threshold af concentration drinking water digestive cancers convincingly identified far regulations adopted weak scientific basis may adequate definitive studies evidence might become sufficient justify monitoring plans persuade countries current limits set maximum level afs drinking water might induce revision existing legislations pointing efficient primary prevention policies pubmed","probabilities":0.9799733,"Title":"Asbestos ingestion and gastrointestinal cancer: a possible underestimated hazard","Abstract":"The presence of asbestos fibres (AFs) in drinking water could be linked with gastrointestinal cancers. However, it is not regulated in several countries due to conflicting evidence. Areas covered: Some reports mainly associated AF ingestion with gastric and colorectal cancer. Experimental evidence suggested a role for timing and extent of exposure, and showed that ingested AFs induce toxic effects on the stomach, ileum and colon, histological alterations and negative effects at a molecular level, cross the placenta and enter foetal organs (including the liver), and seem able to act as a co-carcinogen agent. Occupational studies suggest associations between asbestos exposure and intrahepatic cholangiocarcinoma, and observations exist indicating the possibility that AFs could enter the liver and bile through enteric absorption. Expert commentary: A risk threshold (AF concentration in drinking water) for digestive cancers has not been convincingly identified so far and regulations, where adopted, have weak scientific basis and may not be adequate. With further and more definitive studies, evidence might become sufficient to justify monitoring plans, persuade countries with no current limits to set a maximum level of AFs in drinking water and might induce a revision of the existing legislations, pointing to efficient primary prevention policies.","Source":"PubMed","category":"HUMAN","training_data":"Asbestos ingestion and gastrointestinal cancer: a possible underestimated hazard The presence of asbestos fibres (AFs) in drinking water could be linked with gastrointestinal cancers. However, it is not regulated in several countries due to conflicting evidence. Areas covered: Some reports mainly associated AF ingestion with gastric and colorectal cancer. Experimental evidence suggested a role for timing and extent of exposure, and showed that ingested AFs induce toxic effects on the stomach, ileum and colon, histological alterations and negative effects at a molecular level, cross the placenta and enter foetal organs (including the liver), and seem able to act as a co-carcinogen agent. Occupational studies suggest associations between asbestos exposure and intrahepatic cholangiocarcinoma, and observations exist indicating the possibility that AFs could enter the liver and bile through enteric absorption. Expert commentary: A risk threshold (AF concentration in drinking water) for digestive cancers has not been convincingly identified so far and regulations, where adopted, have weak scientific basis and may not be adequate. With further and more definitive studies, evidence might become sufficient to justify monitoring plans, persuade countries with no current limits to set a maximum level of AFs in drinking water and might induce a revision of the existing legislations, pointing to efficient primary prevention policies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"burden cost gastrointestinal liver pancreatic diseases united states update 2018 background aims estimates disease burden inform national health priorities research clinical care policy aimed estimate health care use spending among gastrointestinal gi including luminal liver pancreatic diseases united states methods estimated health care use spending based currently available administrative claims commercial medicare supplemental plans data gi quality improvement consortium registry national databases results 2015 annual health care expenditures gastrointestinal diseases totaled 135 9 billion hepatitis 23 3 billion esophageal disorders 18 1 billion biliary tract disease 10 3 billion abdominal pain 10 2 billion inflammatory bowel disease 7 2 billion expensive yearly 54 4 million ambulatory visits primary diagnosis gi disease 3 0 million hospital admissions 540 500 cause 30 day readmissions 266 600 new cases gi cancers diagnosed 144 300 cancer deaths year 97 700 deaths non malignant gi diseases estimated 11 0 million colonoscopies 6 1 million upper endoscopies 313 000 flexible sigmoidoscopies 178 400 upper endoscopic ultrasound examinations 169 500 endoscopic retrograde cholangiopancreatography procedures performed annually among average risk persons aged 50 75 years underwent colonoscopy 34 6 1 adenomatous polyps 4 7 1 advanced adenomatous polyps 5 7 1 serrated polyps removed conclusions gi diseases contribute substantially health care use united states total expenditures gi diseases 135 9 billion annually greater common diseases expenditures likely continue increasing pubmed","probabilities":0.9799733,"Title":"Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018","Abstract":"BACKGROUND & AIMS: Estimates of disease burden can inform national health priorities for research, clinical care, and policy. We aimed to estimate health care use and spending among gastrointestinal (GI) (including luminal, liver, and pancreatic) diseases in the United States. METHODS: We estimated health care use and spending based on the most currently available administrative claims from commercial and Medicare Supplemental plans, data from the GI Quality Improvement Consortium Registry, and national databases. RESULTS: In 2015, annual health care expenditures for gastrointestinal diseases totaled $135.9 billion. Hepatitis ($23.3 billion), esophageal disorders ($18.1 billion), biliary tract disease ($10.3 billion), abdominal pain ($10.2 billion), and inflammatory bowel disease ($7.2 billion) were the most expensive. Yearly, there were more than 54.4 million ambulatory visits with a primary diagnosis for a GI disease, 3.0 million hospital admissions, and 540,500 all-cause 30-day readmissions. There were 266,600 new cases of GI cancers diagnosed and 144,300 cancer deaths. Each year, there were 97,700 deaths from non-malignant GI diseases. An estimated 11.0 million colonoscopies, 6.1 million upper endoscopies, 313,000 flexible sigmoidoscopies, 178,400 upper endoscopic ultrasound examinations, and 169,500 endoscopic retrograde cholangiopancreatography procedures were performed annually. Among average-risk persons aged 50-75 years who underwent colonoscopy, 34.6% had 1 or more adenomatous polyps, 4.7% had 1 or more advanced adenomatous polyps, and 5.7% had 1 or more serrated polyps removed. CONCLUSIONS: GI diseases contribute substantially to health care use in the United States. Total expenditures for GI diseases are $135.9 billion annually-greater than for other common diseases. Expenditures are likely to continue increasing.","Source":"PubMed","category":"HUMAN","training_data":"Burden and Cost of Gastrointestinal, Liver, and Pancreatic Diseases in the United States: Update 2018 BACKGROUND & AIMS: Estimates of disease burden can inform national health priorities for research, clinical care, and policy. We aimed to estimate health care use and spending among gastrointestinal (GI) (including luminal, liver, and pancreatic) diseases in the United States. METHODS: We estimated health care use and spending based on the most currently available administrative claims from commercial and Medicare Supplemental plans, data from the GI Quality Improvement Consortium Registry, and national databases. RESULTS: In 2015, annual health care expenditures for gastrointestinal diseases totaled $135.9 billion. Hepatitis ($23.3 billion), esophageal disorders ($18.1 billion), biliary tract disease ($10.3 billion), abdominal pain ($10.2 billion), and inflammatory bowel disease ($7.2 billion) were the most expensive. Yearly, there were more than 54.4 million ambulatory visits with a primary diagnosis for a GI disease, 3.0 million hospital admissions, and 540,500 all-cause 30-day readmissions. There were 266,600 new cases of GI cancers diagnosed and 144,300 cancer deaths. Each year, there were 97,700 deaths from non-malignant GI diseases. An estimated 11.0 million colonoscopies, 6.1 million upper endoscopies, 313,000 flexible sigmoidoscopies, 178,400 upper endoscopic ultrasound examinations, and 169,500 endoscopic retrograde cholangiopancreatography procedures were performed annually. Among average-risk persons aged 50-75 years who underwent colonoscopy, 34.6% had 1 or more adenomatous polyps, 4.7% had 1 or more advanced adenomatous polyps, and 5.7% had 1 or more serrated polyps removed. CONCLUSIONS: GI diseases contribute substantially to health care use in the United States. Total expenditures for GI diseases are $135.9 billion annually-greater than for other common diseases. Expenditures are likely to continue increasing. PubMed","prediction_labels":"HUMAN"},{"cleaned":"largest western experience hepatopancreatoduodenectomy lessons learned 35 cases background hepatopancreatoduodenectomy one complex abdominal operations mainly indicated advanced biliary carcinoma aim present 10 year experience performing operation advanced malignant tumors methods retrospective descriptive study 2004 2014 35 hepatopancreatoduodenectomies performed three different institutions common indication advanced biliary carcinoma 24 patients 68 5 results eighteen patients gallbladder cancer eight klatskin tumors five neuroendocrine tumors liver metastasis one colorectal metastasis invading pancreatic head one intraductal papillary mucinous neoplasm liver metastasis one gastric cancer recurrence liver involvement one ocular melanoma pancreatic head right liver lobe metastasis patients submitted pancreatoduodenectomy liver resection follows eight right trisectionectomies five right lobectomies four left lobectomies 18 central lobectomies ivb v viii overall mortality 34 2 12 35 overall morbidity rate 97 4 conclusion high mortality seen major liver resection performed pancreatoduodenectomy including right lobectomy trisectionectomy liver failure combination pancreatic leak invariably lethal efforts ensure remnant liver 40 50 total liver volume key obtain patient survival pubmed","probabilities":0.9799733,"Title":"THE LARGEST WESTERN EXPERIENCE WITH HEPATOPANCREATODUODENECTOMY: LESSONS LEARNED WITH 35 CASES","Abstract":"BACKGROUND: Hepatopancreatoduodenectomy is one of the most complex abdominal operations mainly indicated in advanced biliary carcinoma. AIM: To present 10-year experience performing this operation in advanced malignant tumors. METHODS: This is a retrospective descriptive study. From 2004 to 2014, 35 hepatopancreatoduodenectomies were performed in three different institutions. The most common indication was advanced biliary carcinoma in 24 patients (68.5%). RESULTS: Eighteen patients had gallbladder cancer, eight Klatskin tumors, five neuroendocrine tumors with liver metastasis, one colorectal metastasis invading the pancreatic head, one intraductal papillary mucinous neoplasm with liver metastasis, one gastric cancer recurrence with liver involvement and one ocular melanoma with pancreatic head and right liver lobe metastasis. All patients were submitted to pancreatoduodenectomy with a liver resection as follows: eight right trisectionectomies, five right lobectomies, four left lobectomies, 18 central lobectomies (IVb, V and VIII). The overall mortality was 34.2% (12/35) and the overall morbidity rate was 97.4%. CONCLUSION: Very high mortality is seen when major liver resection is performed with pancreatoduodenectomy, including right lobectomy and trisectionectomy. Liver failure in combination with a pancreatic leak is invariably lethal. Efforts to ensure a remnant liver over 40-50% of the total liver volume are the key to obtain patient survival.","Source":"PubMed","category":"HUMAN","training_data":"THE LARGEST WESTERN EXPERIENCE WITH HEPATOPANCREATODUODENECTOMY: LESSONS LEARNED WITH 35 CASES BACKGROUND: Hepatopancreatoduodenectomy is one of the most complex abdominal operations mainly indicated in advanced biliary carcinoma. AIM: To present 10-year experience performing this operation in advanced malignant tumors. METHODS: This is a retrospective descriptive study. From 2004 to 2014, 35 hepatopancreatoduodenectomies were performed in three different institutions. The most common indication was advanced biliary carcinoma in 24 patients (68.5%). RESULTS: Eighteen patients had gallbladder cancer, eight Klatskin tumors, five neuroendocrine tumors with liver metastasis, one colorectal metastasis invading the pancreatic head, one intraductal papillary mucinous neoplasm with liver metastasis, one gastric cancer recurrence with liver involvement and one ocular melanoma with pancreatic head and right liver lobe metastasis. All patients were submitted to pancreatoduodenectomy with a liver resection as follows: eight right trisectionectomies, five right lobectomies, four left lobectomies, 18 central lobectomies (IVb, V and VIII). The overall mortality was 34.2% (12/35) and the overall morbidity rate was 97.4%. CONCLUSION: Very high mortality is seen when major liver resection is performed with pancreatoduodenectomy, including right lobectomy and trisectionectomy. Liver failure in combination with a pancreatic leak is invariably lethal. Efforts to ensure a remnant liver over 40-50% of the total liver volume are the key to obtain patient survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"wnt inhibitory factor 1 promoter hypermethylation early event gallbladder cancer tumorigenesis predicts poor survival gallbladder cancer gbc common malignant tumor human biliary tract lack marker timely diagnosis leads extremely poor prognosis study assessed cpg sites wif 1 promoter using bisulfite sequencing pcr methylation specific pcr detect methylation gallbladder cancer cholecystitis tissues wif 1 promoter methylation present 36 50 72 0 gallbladder cancers 5 20 25 0 cholecystitis tissues p 0 000 0 05 suggesting wif 1 promoter methylation might participate malignant transformation cholecystitis gallbladder cancer wif 1 methylation negatively correlated wif 1 protein expression immunohistochemistry demonstrating wif 1 expression downregulated promoter hypermethylation analyzed prognosis 50 gbc patients 5years follow univariate analysis revealed patients hypermethylated wif 1 exhibited worse overall survival hypomethylated wif 1 2 8 137 p 0 004 0 05 furthermore multivariate analysis revealed wif 1 methylation independent prognostic factor 5 year overall survival p 0 011 therefore wif 1 methylation candidate marker early gallbladder cancer diagnosis prognosis stn","probabilities":0.8333333,"Title":"Wnt Inhibitory Factor 1 Promoter Hypermethylation Is An Early Event During Gallbladder Cancer Tumorigenesis That Predicts Poor Survival","Abstract":"Gallbladder cancer (GBC) is the most common malignant tumor in the human biliary tract, but the lack of a marker for timely diagnosis leads to an extremely poor prognosis. In this study, we assessed CpG sites in the WIF-1 promoter using bisulfite sequencing PCR and methylation-specific PCR to detect methylation in gallbladder cancer and cholecystitis tissues. WIF-1 promoter methylation was present in 36 of 50 (72.0%) gallbladder cancers but only 5 of 20 (25.0%) cholecystitis tissues (P=0.000<0.05), suggesting that WIF-1 promoter methylation might participate in the malignant transformation of cholecystitis into gallbladder cancer. WIF-1 methylation was negatively correlated with WIF-1 protein expression by immunohistochemistry, demonstrating that WIF-1 expression is downregulated by promoter hypermethylation. We analyzed the prognosis of 50 GBC patients with 5years of follow-up. Univariate analysis revealed that patients with hypermethylated WIF-1 exhibited worse overall survival than those with hypomethylated WIF-1 (χ2=8.137, P=0.004<0.05). Furthermore, multivariate analysis revealed that WIF-1 methylation was an independent prognostic factor for 5-year overall survival (P=0.011). Therefore, WIF-1 methylation is a candidate as a marker for early gallbladder cancer diagnosis and prognosis.","Source":"STN","category":"HUMAN","training_data":"Wnt Inhibitory Factor 1 Promoter Hypermethylation Is An Early Event During Gallbladder Cancer Tumorigenesis That Predicts Poor Survival Gallbladder cancer (GBC) is the most common malignant tumor in the human biliary tract, but the lack of a marker for timely diagnosis leads to an extremely poor prognosis. In this study, we assessed CpG sites in the WIF-1 promoter using bisulfite sequencing PCR and methylation-specific PCR to detect methylation in gallbladder cancer and cholecystitis tissues. WIF-1 promoter methylation was present in 36 of 50 (72.0%) gallbladder cancers but only 5 of 20 (25.0%) cholecystitis tissues (P=0.000<0.05), suggesting that WIF-1 promoter methylation might participate in the malignant transformation of cholecystitis into gallbladder cancer. WIF-1 methylation was negatively correlated with WIF-1 protein expression by immunohistochemistry, demonstrating that WIF-1 expression is downregulated by promoter hypermethylation. We analyzed the prognosis of 50 GBC patients with 5years of follow-up. Univariate analysis revealed that patients with hypermethylated WIF-1 exhibited worse overall survival than those with hypomethylated WIF-1 (χ2=8.137, P=0.004<0.05). Furthermore, multivariate analysis revealed that WIF-1 methylation was an independent prognostic factor for 5-year overall survival (P=0.011). Therefore, WIF-1 methylation is a candidate as a marker for early gallbladder cancer diagnosis and prognosis. STN","prediction_labels":"HUMAN"},{"cleaned":"svct 2 determines sensitivity ascorbate induced cell death cholangiocarcinoma cell lines patient derived xenografts cholangiocarcinoma cc devastating malignancy late diagnosis poor response conventional chemotherapy recent studies revealed anti cancer effect vitamin c l ascorbic acid ascorbate several types cancer however effect l ascorbic acid aa cc remains elusive herein demonstrated aa induced cytotoxicity cc cells generating intracellular reactive oxygen species ros subsequently dna damage atp depletion mtor pathway inhibition moreover aa worked synergistically chemotherapeutic agent cisplatin impair cc cells growth vitro vivo intriguingly sodium dependent vitamin c transporter 2 svct 2 expression inversely correlated ic50 values aa knockdown svct 2 dramatically alleviated dna damage atp depletion inhibition mtor pathway induced aa furthermore svct 2 knockdown endowed cc cells resistance aa treatment finally inhibitory effects aa confirmed patient derived cc xenograft models thus results unravel therapeutic potential aa alone combination cisplatin cc svct2 expression level may serve positive outcome predictor aa treatment cc stn","probabilities":0.9467213,"Title":"Svct-2 Determines The Sensitivity To Ascorbate-Induced Cell Death In Cholangiocarcinoma Cell Lines And Patient Derived Xenografts","Abstract":"Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C (l-ascorbic acid, ascorbate) in several types of cancer. However, the effect of l-ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo. Intriguingly, sodium-dependent vitamin C transporter 2 (SVCT-2) expression was inversely correlated with IC50 values of AA. Knockdown of SVCT-2 dramatically alleviated DNA damage, ATP depletion, and inhibition of mTOR pathway induced by AA. Furthermore, SVCT-2 knockdown endowed CC cells with the resistance to AA treatment. Finally, the inhibitory effects of AA were further confirmed in patient-derived CC xenograft models. Thus, our results unravel therapeutic potential of AA alone or in combination with cisplatin for CC. SVCT2 expression level may serve as a positive outcome predictor for AA treatment in CC.","Source":"STN","category":"ANIMAL","training_data":"Svct-2 Determines The Sensitivity To Ascorbate-Induced Cell Death In Cholangiocarcinoma Cell Lines And Patient Derived Xenografts Cholangiocarcinoma (CC) is a devastating malignancy with late diagnosis and poor response to conventional chemotherapy. Recent studies have revealed anti-cancer effect of vitamin C (l-ascorbic acid, ascorbate) in several types of cancer. However, the effect of l-ascorbic acid (AA) in CC remains elusive. Herein, we demonstrated that AA induced cytotoxicity in CC cells by generating intracellular reactive oxygen species (ROS), and subsequently DNA damage, ATP depletion, mTOR pathway inhibition. Moreover, AA worked synergistically with chemotherapeutic agent cisplatin to impair CC cells growth both in vitro and in vivo. Intriguingly, sodium-dependent vitamin C transporter 2 (SVCT-2) expression was inversely correlated with IC50 values of AA. Knockdown of SVCT-2 dramatically alleviated DNA damage, ATP depletion, and inhibition of mTOR pathway induced by AA. Furthermore, SVCT-2 knockdown endowed CC cells with the resistance to AA treatment. Finally, the inhibitory effects of AA were further confirmed in patient-derived CC xenograft models. Thus, our results unravel therapeutic potential of AA alone or in combination with cisplatin for CC. SVCT2 expression level may serve as a positive outcome predictor for AA treatment in CC. STN","prediction_labels":"ANIMAL"},{"cleaned":"triptolide trail combination enhances cell death via apoptosis cholangiocarcinoma cells human cholangiocarcinoma tumor extra intra hepatic cholangiocytes remains difficult tumor cure overall survival rate less 20 hypothesis inhibition hsp 70 combination activation tumor death receptors lead increased tumor killing death receptor 4 5 dr4 dr5 known overexpressed several cancer types activation trail known induce cell death tumors however cholangiocarcinoma trail marginally effective objective determine combination trail triptolide induce significant cell death cholangiocarcinoma cholangiocarcinoma cell lines kmch kmbc oz skcha 1 one pancreatic cancer cell line incubated various doses triptolide trail alone combination cell viability assessed 24 48 hours annexin caspase 3 measured 24 hours triptolide trail combination treatment using trail triptolide determine percent cell apoptosis caspase 3 activity western blots assessed protein levels parp xiap combination treatment trail triptolide decreased cell viability cell lines 48 hours either drug used alone decrease viability statistically significant mediated increase annexin staining caspase 3 activity western blot analysis demonstrated dose dependent relationship increased parp cleavage decreased xiap increased triptolide concentration trail triptolide combination decreased cell viability enhanced cell death via apoptosis furthermore western blot analysis suggests triptolide sensitizes cells trail induced apoptotic cell death inhibiting expression xiap protein known inhibit apoptosis results demonstrate trail triptolide enhance apoptosis cholangiocarcinoma cell lines google scholar","probabilities":0.9467213,"Title":"Triptolide And Trail Combination Enhances Cell Death Via Apoptosis In Cholangiocarcinoma Cells","Abstract":"Human cholangiocarcinoma tumor of the extra- or intra-hepatic cholangiocytes remains a difficult tumor to cure with an overall survival rate of less than 20%. It is our hypothesis that inhibition of HSP-70 in combination with the activation of tumor death receptors will lead to increased tumor killing. Death Receptor 4 and 5 (DR4 and DR5) are known to be overexpressed in several cancer types and their activation by TRAIL is known to induce cell death in those tumors. However, in cholangiocarcinoma TRAIL is only marginally effective. Our objective was to determine if the combination of TRAIL and triptolide could induce significant cell death in cholangiocarcinoma. Cholangiocarcinoma cell lines (KMCH, KMBC, Oz and SkChA-1) and one pancreatic cancer cell line were incubated with various doses of triptolide and TRAIL alone and in combination; cell viability was assessed at 24 and 48 hours. Annexin and caspase-3 were measured after 24 hours of triptolide, TRAIL or combination treatment using TRAIL and triptolide to determine the percent of cell apoptosis and caspase-3 activity. Western blots assessed protein levels of PARP and XIAP. Combination treatment with TRAIL and triptolide decreased cell viability in all cell lines at 48 hours more than when either drug was used alone. This decrease in viability was statistically significant and mediated by an increase in annexin staining and caspase-3 activity. Western blot analysis demonstrated a dose dependent relationship between increased PARP cleavage, decreased XIAP and increased triptolide concentration. TRAIL and triptolide in combination decreased cell viability and enhanced cell death via apoptosis. Furthermore, Western blot analysis suggests that triptolide sensitizes cells to TRAIL-induced apoptotic cell death by inhibiting the expression of XIAP, a protein known to inhibit apoptosis. These results demonstrate that TRAIL and triptolide enhance apoptosis in cholangiocarcinoma cell lines.","Source":"Google Scholar","category":"ANIMAL","training_data":"Triptolide And Trail Combination Enhances Cell Death Via Apoptosis In Cholangiocarcinoma Cells Human cholangiocarcinoma tumor of the extra- or intra-hepatic cholangiocytes remains a difficult tumor to cure with an overall survival rate of less than 20%. It is our hypothesis that inhibition of HSP-70 in combination with the activation of tumor death receptors will lead to increased tumor killing. Death Receptor 4 and 5 (DR4 and DR5) are known to be overexpressed in several cancer types and their activation by TRAIL is known to induce cell death in those tumors. However, in cholangiocarcinoma TRAIL is only marginally effective. Our objective was to determine if the combination of TRAIL and triptolide could induce significant cell death in cholangiocarcinoma. Cholangiocarcinoma cell lines (KMCH, KMBC, Oz and SkChA-1) and one pancreatic cancer cell line were incubated with various doses of triptolide and TRAIL alone and in combination; cell viability was assessed at 24 and 48 hours. Annexin and caspase-3 were measured after 24 hours of triptolide, TRAIL or combination treatment using TRAIL and triptolide to determine the percent of cell apoptosis and caspase-3 activity. Western blots assessed protein levels of PARP and XIAP. Combination treatment with TRAIL and triptolide decreased cell viability in all cell lines at 48 hours more than when either drug was used alone. This decrease in viability was statistically significant and mediated by an increase in annexin staining and caspase-3 activity. Western blot analysis demonstrated a dose dependent relationship between increased PARP cleavage, decreased XIAP and increased triptolide concentration. TRAIL and triptolide in combination decreased cell viability and enhanced cell death via apoptosis. Furthermore, Western blot analysis suggests that triptolide sensitizes cells to TRAIL-induced apoptotic cell death by inhibiting the expression of XIAP, a protein known to inhibit apoptosis. These results demonstrate that TRAIL and triptolide enhance apoptosis in cholangiocarcinoma cell lines. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"elevation o glcnacylation enhances progression cholangiocarcinoma cells o glcnacylation post translational modification nucleocytoplasmic proteins single n acetylglucosamine glcnac process controlled two enzymes o glcnac transferase ogt transfers glcnac serine threonine protein yielding o glcnacylated proteins ogps o glcnacase oga catalyzes reversed reaction ogps important many cellular processes including tumor progression expression ogt cholangiocarcinoma cca tissues correlation shorter survival cca patients reported recently addition knockdown ogt alleviated migration invasion cca cell lines study elucidate novel ogps modulate progression cca cells enhance ogps cca cells suppression oga using pugnac oga inhibitor used model study increase o glcnacylation via pugnac treatment significantly increased cca cell migration invasion two cca cell lines ogps related progression cca determined using click o glcnac enzymatic labeling system label o glcnacylated peptides identified q exactive orbitrap mass spectrometer majority ogps found kku 213 kku 214 cells nucleocytoplasmic proteins 21 ogps commonly found cell lines almost similar intensity 12 yet reported o glcnacylated forms e g solute carrier family 3 member 2 meprin subunit alpha heterogeneous nuclear ribonucleoprotein k calnexin etc novel ogp candidates selected confirmed o glcnacylated forms using immunoprecipitation swga pull assay studies required demonstrate o glcnacylated site novel ogp candidate role related cancer progression google scholar","probabilities":0.9467213,"Title":"Elevation Of O-Glcnacylation Enhances Progression Of Cholangiocarcinoma Cells","Abstract":"O-GlcNAcylation is a post-translational modification of nucleocytoplasmic proteins with a single N-acetylglucosamine (GlcNAc). This process is controlled by two enzymes; the O-GlcNAc transferase (OGT) which transfers GlcNAc to serine or threonine of protein yielding the O-GlcNAcylated proteins (OGPs); and O-GlcNAcase (OGA) which catalyzes the reversed reaction. The OGPs are important in many cellular processes including tumor progression. Over-expression of OGT in cholangiocarcinoma (CCA) tissues and its correlation with shorter survival of CCA patients have been reported recently. In addition, knockdown of OGT alleviated the migration/invasion of CCA cell lines. This study, we further elucidate the novel OGPs that modulate the progression of CCA cells. To enhance the OGPs in CCA cells, suppression of OGA using PUGNAc, an OGA inhibitor, was used as the model of study. Increase of O-GlcNAcylation via PUGNAc treatment significantly increased CCA cell migration and invasion in two CCA cell lines. The OGPs related to the progression of CCA were further determined using Click-iT™ O-GlcNAc Enzymatic Labeling System to label O-GlcNAcylated peptides and identified by Q-Exactive Orbitrap mass spectrometer. Majority of OGPs found in KKU-213 and KKU-214 cells were nucleocytoplasmic proteins. There were 21 OGPs commonly found in both cell lines with almost similar intensity, of which 12 have not yet been reported for their O-GlcNAcylated forms, e.g., the solute carrier family 3 member 2, meprin A subunit alpha, heterogeneous nuclear ribonucleoprotein K, and calnexin, etc. The novel OGP candidates were selected and confirmed for the O-GlcNAcylated forms using immunoprecipitation and sWGA pull-down assay. Further studies are required to demonstrate the O-GlcNAcylated site of the novel OGP candidate and its role related to cancer progression.","Source":"Google Scholar","category":"ANIMAL","training_data":"Elevation Of O-Glcnacylation Enhances Progression Of Cholangiocarcinoma Cells O-GlcNAcylation is a post-translational modification of nucleocytoplasmic proteins with a single N-acetylglucosamine (GlcNAc). This process is controlled by two enzymes; the O-GlcNAc transferase (OGT) which transfers GlcNAc to serine or threonine of protein yielding the O-GlcNAcylated proteins (OGPs); and O-GlcNAcase (OGA) which catalyzes the reversed reaction. The OGPs are important in many cellular processes including tumor progression. Over-expression of OGT in cholangiocarcinoma (CCA) tissues and its correlation with shorter survival of CCA patients have been reported recently. In addition, knockdown of OGT alleviated the migration/invasion of CCA cell lines. This study, we further elucidate the novel OGPs that modulate the progression of CCA cells. To enhance the OGPs in CCA cells, suppression of OGA using PUGNAc, an OGA inhibitor, was used as the model of study. Increase of O-GlcNAcylation via PUGNAc treatment significantly increased CCA cell migration and invasion in two CCA cell lines. The OGPs related to the progression of CCA were further determined using Click-iT™ O-GlcNAc Enzymatic Labeling System to label O-GlcNAcylated peptides and identified by Q-Exactive Orbitrap mass spectrometer. Majority of OGPs found in KKU-213 and KKU-214 cells were nucleocytoplasmic proteins. There were 21 OGPs commonly found in both cell lines with almost similar intensity, of which 12 have not yet been reported for their O-GlcNAcylated forms, e.g., the solute carrier family 3 member 2, meprin A subunit alpha, heterogeneous nuclear ribonucleoprotein K, and calnexin, etc. The novel OGP candidates were selected and confirmed for the O-GlcNAcylated forms using immunoprecipitation and sWGA pull-down assay. Further studies are required to demonstrate the O-GlcNAcylated site of the novel OGP candidate and its role related to cancer progression. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"matching genomic molecular aberrations molecular targeted agents biliary tract cancers ideal playground biliary tract cancers btcs heterogeneous group tumours geographical discrepancies terms incidence risk factors however convergent genomic epigenetic mutational landscape emerges genome wide screens btcs south east asia latin america western world specificities observed alterations anatomical subtypes frequent fibroblast growth factor receptor 2 fgfr2 isocitrate dehydrogenase 1 2 idh1 2 alterations specific intrahepatic cholangiocarcinomas iccs whereas frequent erbb2 oncogene alterations specific extrahepatic cholangiocarcinomas eccs gallbladder carcinomas gbcs outcome patients btcs treated molecular targeted agents mtas alone combination conventional chemotherapy non biology driven trials remains poor exceed outcome patients treated chemotherapy alone encouraging reports biology driven therapeutic approaches accelerate clinical development mtas btcs additionally frequent epigenetic aberrations idh1 2 mutations switch sucrose non fermenting swi snf complex dysfunctions suggest epidrugs must also considered review expose rationale feasibility biologically drive treatment btc patients pubmed","probabilities":0.9799733,"Title":"Matching genomic molecular aberrations with molecular targeted agents: Are biliary tract cancers an ideal playground?","Abstract":"Biliary tract cancers (BTCs) are a heterogeneous group of tumours with geographical discrepancies in terms of incidence and risk factors. However, a convergent genomic and epigenetic mutational landscape emerges from the genome-wide screens of BTCs in South East Asia, Latin America and in the Western World. Specificities are observed for some alterations and anatomical subtypes: frequent fibroblast growth factor receptor 2 (FGFR2) and isocitrate dehydrogenase 1/2 (IDH1/2) alterations are specific to intrahepatic cholangiocarcinomas (ICCs), whereas frequent ERBB2 oncogene alterations are specific to extrahepatic cholangiocarcinomas (ECCs) and gallbladder carcinomas (GBCs). Until now, the outcome of patients with BTCs treated by molecular targeted agents (MTAs) alone or in combination with conventional chemotherapy in non-biology driven trials remains poor and does not exceed the outcome of patients treated with chemotherapy alone. Encouraging reports of biology-driven therapeutic approaches should accelerate the clinical development of MTAs in BTCs. Additionally, frequent epigenetic aberrations such as IDH1/2 mutations and switch/sucrose non-fermenting (SWI/SNF) complex dysfunctions suggest that epidrugs must also be considered. In this review, we expose the rationale and feasibility to biologically drive the treatment of BTC patients.","Source":"PubMed","category":"HUMAN","training_data":"Matching genomic molecular aberrations with molecular targeted agents: Are biliary tract cancers an ideal playground? Biliary tract cancers (BTCs) are a heterogeneous group of tumours with geographical discrepancies in terms of incidence and risk factors. However, a convergent genomic and epigenetic mutational landscape emerges from the genome-wide screens of BTCs in South East Asia, Latin America and in the Western World. Specificities are observed for some alterations and anatomical subtypes: frequent fibroblast growth factor receptor 2 (FGFR2) and isocitrate dehydrogenase 1/2 (IDH1/2) alterations are specific to intrahepatic cholangiocarcinomas (ICCs), whereas frequent ERBB2 oncogene alterations are specific to extrahepatic cholangiocarcinomas (ECCs) and gallbladder carcinomas (GBCs). Until now, the outcome of patients with BTCs treated by molecular targeted agents (MTAs) alone or in combination with conventional chemotherapy in non-biology driven trials remains poor and does not exceed the outcome of patients treated with chemotherapy alone. Encouraging reports of biology-driven therapeutic approaches should accelerate the clinical development of MTAs in BTCs. Additionally, frequent epigenetic aberrations such as IDH1/2 mutations and switch/sucrose non-fermenting (SWI/SNF) complex dysfunctions suggest that epidrugs must also be considered. In this review, we expose the rationale and feasibility to biologically drive the treatment of BTC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"angiotensin ii induces tumor progression fibrosis intrahepatic cholangiocarcinoma interaction hepatic stellate cells intrahepatic cholangiocarcinoma icc characterized highly fatal tumor poor prognosis strong progression early invasion widespread metastasis rich cancerous stroma although widely accepted fibroblasts facilitate stromal fibrosis tumor progression mechanisms interaction cancer cells activated fibroblasts fully elucidated thus far study demonstrate presence angiotensin ii angii icc tissues explore interaction hepatic stellate cells hscs icc cells one sources stromal fibrosis tumor progression interaction angii angii type 1 receptor 1 axis concentrations angii icc tissues significantly higher hcc normal liver two human icc cell lines hucct 1 ccks 1 human hsc cell line li 90 expressed 1 mrna protein proliferative activity icc cells hscs angii added dose dependently increased 1 antagonist inhibited proliferative effects hscs angii added showed higher expression smooth muscle actin sma marker activated hscs myofibroblasts glial fibrillary acidic protein gfap specific marker hscs collagen type control cells 1 antagonist also inhibited activation transformation hscs stimulated angii findings suggested locally formed angii icc tissues plays role proliferation activation icc cells hscs expressing 1 growth factor autocrine paracrine fashions mechanistic findings provide first insight autocrine paracrine angii initiated signaling pathway regulates icc proliferation fibrosis stn","probabilities":0.9467213,"Title":"Angiotensin Ii Induces Tumor Progression And Fibrosis In Intrahepatic Cholangiocarcinoma Through An Interaction With Hepatic Stellate Cells","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is characterized as a highly fatal tumor with poor prognosis because of its strong progression, early invasion, widespread metastasis and rich cancerous stroma. Although it is widely accepted that fibroblasts facilitate stromal fibrosis and tumor progression, the mechanisms of the interaction between cancer cells and activated fibroblasts have not been fully elucidated thus far. In this study, we demonstrate the presence of angiotensin II (AngII) in ICC tissues and explore the interaction between hepatic stellate cells (HSCs) and ICC cells as one of the sources of stromal fibrosis and tumor progression through the interaction of the AngII/AngII type 1 receptor (AT-1) axis. The concentrations of AngII in ICC tissues were significantly higher than those of HCC and normal liver. Two human ICC cell lines (HuCCT-1, CCKS-1) and a human HSC cell line (LI-90) expressed AT-1 mRNA and protein. The proliferative activity of ICC cells and HSCs to which AngII was added dose-dependently increased and AT-1 antagonist inhibited the proliferative effects. HSCs to which AngII was added showed a higher expression of α-smooth muscle actin (α-SMA, a marker of activated HSCs and myofibroblasts), glial fibrillary acidic protein (GFAP, a specific marker of HSCs) and collagen type I than control cells. AT-1 antagonist also inhibited the activation and transformation of HSCs stimulated by AngII. These findings suggested that locally formed AngII in ICC tissues plays a role in the proliferation and activation of ICC cells and HSCs expressing AT-1 as a growth factor in autocrine and paracrine fashions. Our mechanistic findings provide the first insight into an autocrine and paracrine AngII-initiated signaling pathway that regulates ICC proliferation and fibrosis.","Source":"STN","category":"ANIMAL","training_data":"Angiotensin Ii Induces Tumor Progression And Fibrosis In Intrahepatic Cholangiocarcinoma Through An Interaction With Hepatic Stellate Cells Intrahepatic cholangiocarcinoma (ICC) is characterized as a highly fatal tumor with poor prognosis because of its strong progression, early invasion, widespread metastasis and rich cancerous stroma. Although it is widely accepted that fibroblasts facilitate stromal fibrosis and tumor progression, the mechanisms of the interaction between cancer cells and activated fibroblasts have not been fully elucidated thus far. In this study, we demonstrate the presence of angiotensin II (AngII) in ICC tissues and explore the interaction between hepatic stellate cells (HSCs) and ICC cells as one of the sources of stromal fibrosis and tumor progression through the interaction of the AngII/AngII type 1 receptor (AT-1) axis. The concentrations of AngII in ICC tissues were significantly higher than those of HCC and normal liver. Two human ICC cell lines (HuCCT-1, CCKS-1) and a human HSC cell line (LI-90) expressed AT-1 mRNA and protein. The proliferative activity of ICC cells and HSCs to which AngII was added dose-dependently increased and AT-1 antagonist inhibited the proliferative effects. HSCs to which AngII was added showed a higher expression of α-smooth muscle actin (α-SMA, a marker of activated HSCs and myofibroblasts), glial fibrillary acidic protein (GFAP, a specific marker of HSCs) and collagen type I than control cells. AT-1 antagonist also inhibited the activation and transformation of HSCs stimulated by AngII. These findings suggested that locally formed AngII in ICC tissues plays a role in the proliferation and activation of ICC cells and HSCs expressing AT-1 as a growth factor in autocrine and paracrine fashions. Our mechanistic findings provide the first insight into an autocrine and paracrine AngII-initiated signaling pathway that regulates ICC proliferation and fibrosis. STN","prediction_labels":"ANIMAL"},{"cleaned":"association low level vitamin retinol binding protein liver complications patients primary sclerosing cholangitis background recent study showed vitamin deficiency mice may contribute increased intraluminal pressure cholangioles resulting liver damage aimed determine association vitamin retinol binding protein rbp levels outcome liver complications patients psc methods used prospectively collected data multicenter randomized trial high dose udca psc versus placebo outcomes liver complications presence liver related death transplant development varices cholangiocarcinoma progression cirrhosis serum samples analyzed 76 150 patients psc 50 7 serum available vitamin level measured standard high pressure liquid chromatography serum rbp levels measured nephelometryin academic medical center amsterdam performing assays blinded results primary outcome results median age range 44 years 17 9 75 6 51 3 male low vitamin low rbp levels found 26 3 44 7 patients respectively eighteen patients 23 7 low level vitamin rbp 76 patients 68 available results vitamin rbp level twenty two patients 32 4 developed liver complications follow linear regression vitamin level significant relationship rbp level p 0 0001 r square 0 4 total bilirubin level p 0 0001 rsquare 0 2 andplatelet counts p 0 0002 r square 0 2 univariate logisticregression model patients liver complications significantly higher mayo risk score advanced liver fibrosis varices baseline often higher total bilirubin higher alp higher ast alt ratio baseline lower albumin lower level vitamin rbp baseline without liver complications p 0 05 multivariable logistic analysis presence low level vitamin rbp higher alp level significantly associated presence liver complications 6 3 95 ci 1 6 25 5 1 0 95 ci 1 0 1 004 respectively conclusions one fourth patientswith psc low level vitamin rbp presence low level vitamin rbp higher alp level baseline associated increasing risk liver complications unknown causal connection low vitamin rbp levels liver complications google scholar","probabilities":0.5555556,"Title":"The Association Of Low Level Of Both Vitamin A And Retinol Binding Protein With The Liver Complications In Patients With Primary Sclerosing Cholangitis","Abstract":"Background: A recent study showed that vitamin A deficiency in mice may contribute to increased intraluminal pressure in the cholangioles resulting in liver damage. We aimed to determine the association of vitamin A and retinol binding protein (RBP) levels and the outcome of liver complications in patients with PSC. Methods: We used prospectively collected data from a multicenter randomized trial of high dose UDCA for PSC versus placebo. The outcomes of liver complications were the presence of liver-related death, transplant, development of varices, cholangiocarcinoma or progression to cirrhosis. Serum samples were analyzed from all 76 of the 150 patients with PSC (50.7%)who had serum available. Vitamin A level was measured by standard high-pressure liquid chromatography and serum RBP levels was measured by nephelometryin the Academic Medical Center, Amsterdam. Those performing the assays were blinded to the results of primary outcome. Results: The median age (range) was 44 years (17.9, 75.6) with 51.3% male. Low vitamin A and low RBP levels were found in 26.3% and 44.7% of patients, respectively. Eighteen patients (23.7%) had low level of both vitamin A and RBP. Of the 76 patients, 68 had available results of both vitamin A and RBP level. Twenty-two patients (32.4%) developed liver complications during follow-up. By linear regression, vitamin A level had a significant relationship with RBP level (P <0.0001, R-square=0.4), total bilirubin level (P = 0.0001, Rsquare=0.2), andplatelet counts(P =0.0002, R-square=0.2).In univariate logisticregression model, patients with liver complications had significantly higher Mayo risk score, had advanced liver fibrosis and varices at baseline more often, higher total bilirubin, higher ALP, and higher AST/ALT ratio at baseline, lower albumin, lower level of both vitamin A and RBP at baseline than those without liver complications (P<0.05). By a multivariable logistic analysis, presence of low level of both vitamin A and RBP and higher ALP level were significantly associated with the presence of liver complications (OR= 6.3, 95%CI=1.6-25.5 and 1.0, 95%CI=1.0-1.004,respectively). Conclusions: One-fourth of patientswith PSC had low level of both vitamin A and RBP. Presence of low level of both vitamin A and RBP and higher ALP level at baseline were associated with the increasing risk of liver complications. It is unknown if there is a causal connection between low vitamin A and RBP levels and the liver complications.","Source":"Google Scholar","category":"ANIMAL","training_data":"The Association Of Low Level Of Both Vitamin A And Retinol Binding Protein With The Liver Complications In Patients With Primary Sclerosing Cholangitis Background: A recent study showed that vitamin A deficiency in mice may contribute to increased intraluminal pressure in the cholangioles resulting in liver damage. We aimed to determine the association of vitamin A and retinol binding protein (RBP) levels and the outcome of liver complications in patients with PSC. Methods: We used prospectively collected data from a multicenter randomized trial of high dose UDCA for PSC versus placebo. The outcomes of liver complications were the presence of liver-related death, transplant, development of varices, cholangiocarcinoma or progression to cirrhosis. Serum samples were analyzed from all 76 of the 150 patients with PSC (50.7%)who had serum available. Vitamin A level was measured by standard high-pressure liquid chromatography and serum RBP levels was measured by nephelometryin the Academic Medical Center, Amsterdam. Those performing the assays were blinded to the results of primary outcome. Results: The median age (range) was 44 years (17.9, 75.6) with 51.3% male. Low vitamin A and low RBP levels were found in 26.3% and 44.7% of patients, respectively. Eighteen patients (23.7%) had low level of both vitamin A and RBP. Of the 76 patients, 68 had available results of both vitamin A and RBP level. Twenty-two patients (32.4%) developed liver complications during follow-up. By linear regression, vitamin A level had a significant relationship with RBP level (P <0.0001, R-square=0.4), total bilirubin level (P = 0.0001, Rsquare=0.2), andplatelet counts(P =0.0002, R-square=0.2).In univariate logisticregression model, patients with liver complications had significantly higher Mayo risk score, had advanced liver fibrosis and varices at baseline more often, higher total bilirubin, higher ALP, and higher AST/ALT ratio at baseline, lower albumin, lower level of both vitamin A and RBP at baseline than those without liver complications (P<0.05). By a multivariable logistic analysis, presence of low level of both vitamin A and RBP and higher ALP level were significantly associated with the presence of liver complications (OR= 6.3, 95%CI=1.6-25.5 and 1.0, 95%CI=1.0-1.004,respectively). Conclusions: One-fourth of patientswith PSC had low level of both vitamin A and RBP. Presence of low level of both vitamin A and RBP and higher ALP level at baseline were associated with the increasing risk of liver complications. It is unknown if there is a causal connection between low vitamin A and RBP levels and the liver complications. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"expression programmed death ligand 1 associated prognosis intrahepatic cholangiocarcinoma background programmed death ligand 1 pd l1 expressed many malignancies plays critical role escape immune surveillance inhibition receptor programmed death 1 role pd l1 intrahepatic cholangiocarcinoma icc mechanisms regulation however remain largely unknown aims analyze expression prognostic significance pd l1 icc study regulatory mechanisms pd l1 methods samples obtained 125 patients diagnosed icc eastern hepatobiliary surgery hospital january 2012 january 2013 records patient analyzed examine relationship pd l1 clinical data vitro experiments performed investigate relationship pd l1 il 6 mtor signaling pathway feedback mechanism pathway pd l1 results expression pd l1 closely related tumor vascular invasion lymphatic metastasis tnm staging high pd l1 expression closely related poor prognosis icc mechanically il 6 induces pd l1 expression mtor signaling icc cells addition pd l1 negative feedback inhibition effect akt signaling conclusions summary high pd l1 expression found associated poor prognosis il 6 mtor pathway upregulates expression pd l1 thus promoting tumor invasion pd l1 negatively inhibits akt pathway google scholar","probabilities":0.9799733,"Title":"Expression Of Programmed Death Ligand 1 Is Associated With The Prognosis Of Intrahepatic Cholangiocarcinoma","Abstract":"Background\nProgrammed death ligand 1 (PD-L1) is expressed in many malignancies and plays a critical role in escape from immune surveillance through inhibition of its receptor programmed death 1. The role of PD-L1 in intrahepatic cholangiocarcinoma (ICC) and mechanisms of its regulation, however, remain largely unknown.\nAims\nTo analyze the expression and prognostic significance of PD-L1 in ICC and to study the regulatory mechanisms of PD-L1.\nMethods\nSamples were obtained from 125 patients diagnosed with ICC in the Eastern Hepatobiliary Surgery Hospital from January 2012 to January 2013. The records of each patient were analyzed to examine the relationship between PD-L1 and clinical data. In vitro experiments were performed to investigate the relationship between PD-L1 and the IL-6/mTOR signaling pathway and the feedback mechanism pathway of PD-L1.\nResults\nExpression of PD-L1 is closely related to tumor vascular invasion, lymphatic metastasis and TNM staging. High PD-L1 expression is closely related to poor prognosis in ICC. Mechanically, IL-6 induces PD-L1 expression through mTOR signaling in ICC cells. In addition, PD-L1 has a negative feedback inhibition effect on AKT signaling.\nConclusions\nIn summary, high PD-L1 expression was found to be associated with poor prognosis. The IL-6/mTOR pathway upregulates expression of PD-L1, thus promoting tumor invasion, and PD-L1 negatively inhibits the AKT pathway.","Source":"Google Scholar","category":"ANIMAL","training_data":"Expression Of Programmed Death Ligand 1 Is Associated With The Prognosis Of Intrahepatic Cholangiocarcinoma Background\nProgrammed death ligand 1 (PD-L1) is expressed in many malignancies and plays a critical role in escape from immune surveillance through inhibition of its receptor programmed death 1. The role of PD-L1 in intrahepatic cholangiocarcinoma (ICC) and mechanisms of its regulation, however, remain largely unknown.\nAims\nTo analyze the expression and prognostic significance of PD-L1 in ICC and to study the regulatory mechanisms of PD-L1.\nMethods\nSamples were obtained from 125 patients diagnosed with ICC in the Eastern Hepatobiliary Surgery Hospital from January 2012 to January 2013. The records of each patient were analyzed to examine the relationship between PD-L1 and clinical data. In vitro experiments were performed to investigate the relationship between PD-L1 and the IL-6/mTOR signaling pathway and the feedback mechanism pathway of PD-L1.\nResults\nExpression of PD-L1 is closely related to tumor vascular invasion, lymphatic metastasis and TNM staging. High PD-L1 expression is closely related to poor prognosis in ICC. Mechanically, IL-6 induces PD-L1 expression through mTOR signaling in ICC cells. In addition, PD-L1 has a negative feedback inhibition effect on AKT signaling.\nConclusions\nIn summary, high PD-L1 expression was found to be associated with poor prognosis. The IL-6/mTOR pathway upregulates expression of PD-L1, thus promoting tumor invasion, and PD-L1 negatively inhibits the AKT pathway. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic relevance lymph node status patients ampullary adenocarcinoma radical resection followed adjuvant treatment purpose attempts made revise nodal stage due simplicity current n staging system ampullary adenocarcinoma however disease rarity studies assessing prognostic impact lymph node ln parameters methods retrospectively analyzed 120 patients underwent radical resection followed adjuvant chemoradiotherapy ampullary adenocarcinoma effect ln parameters number total harvest lns number metastatic ln mln lymph node ratio lnr log odds positive lns lodds overall survival os locoregional relapse free survival lrfs distant metastasis free survival evaluated cutoff points mln lnr lodds determined using maximal 2 method results fifty seven patients 48 staged pn1 survival significantly decreased compared pn0 patients also significant difference patients mln 0 vs 1 univariate analyses mln 0 1 vs 2 lnr 17 vs 17 perineural invasion common prognosticators os lrfs distant metastasis free survival influenced ln status addition multivariate analysis revealed among ln parameters lnr able independently predict os lrfs conclusions lnr performs better ln related parameters predicting survival radical resection followed adjuvant treatment survival patients one positive ln seem differ patients without ln metastasis pubmed","probabilities":0.9799733,"Title":"Prognostic relevance of lymph node status for patients with ampullary adenocarcinoma after radical resection followed by adjuvant treatment","Abstract":"PURPOSE: Attempts have been made to revise the nodal stage due to simplicity of current N staging system in ampullary adenocarcinoma. However, because of the disease rarity, there have only been a few studies assessing the prognostic impact of lymph node (LN) parameters. METHODS: We retrospectively analyzed 120 patients who underwent radical resection followed by adjuvant chemoradiotherapy for ampullary adenocarcinoma. The effect of LN parameters (number of total harvest LNs, number of metastatic LN (MLN), lymph node ratio (LNR), and log odds of positive LNs (LODDS)) on overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival were evaluated. Cutoff points of MLN, LNR and LODDs were determined using maximal χ(2) method. RESULTS: Fifty-seven patients (48%) were staged as pN1 and their survival was not significantly decreased compared with pN0 patients. There was also no significant difference between patients with MLN 0 vs. 1. In univariate analyses, MLN (0-1 vs. ≥2), LNR (≤17% vs. >17%) and perineural invasion were common prognosticators for OS and LRFS. Distant metastasis-free survival was not influenced by LN status. In addition, multivariate analysis revealed that among the LN parameters, LNR was able to independently predict both OS and LRFS. CONCLUSIONS: LNR performs better than other LN related parameters for predicting survival. After radical resection followed by adjuvant treatment, survival of patients with one positive LN does not seem to differ from patients without LN metastasis.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic relevance of lymph node status for patients with ampullary adenocarcinoma after radical resection followed by adjuvant treatment PURPOSE: Attempts have been made to revise the nodal stage due to simplicity of current N staging system in ampullary adenocarcinoma. However, because of the disease rarity, there have only been a few studies assessing the prognostic impact of lymph node (LN) parameters. METHODS: We retrospectively analyzed 120 patients who underwent radical resection followed by adjuvant chemoradiotherapy for ampullary adenocarcinoma. The effect of LN parameters (number of total harvest LNs, number of metastatic LN (MLN), lymph node ratio (LNR), and log odds of positive LNs (LODDS)) on overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival were evaluated. Cutoff points of MLN, LNR and LODDs were determined using maximal χ(2) method. RESULTS: Fifty-seven patients (48%) were staged as pN1 and their survival was not significantly decreased compared with pN0 patients. There was also no significant difference between patients with MLN 0 vs. 1. In univariate analyses, MLN (0-1 vs. ≥2), LNR (≤17% vs. >17%) and perineural invasion were common prognosticators for OS and LRFS. Distant metastasis-free survival was not influenced by LN status. In addition, multivariate analysis revealed that among the LN parameters, LNR was able to independently predict both OS and LRFS. CONCLUSIONS: LNR performs better than other LN related parameters for predicting survival. After radical resection followed by adjuvant treatment, survival of patients with one positive LN does not seem to differ from patients without LN metastasis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"correlation jaundice prognosis gallbladder cancer background explore correlation jaundice prognosis gallbladder cancer methods retrospectively analyzed 181 patients gallbladder cancer treated department december 2002 june 2010 jaundice found 91 patients 90 patients without jaundice results median survival time patients jaundice 8 8 1 6 months signi cantly shorter one without jaundice 24 8 3 0 months p 0 01 patients jaundice stage iii iv gallbladder cancer median survival time shorter stage iii iv gallbladder cancer patients without jaundice 16 3 2 3 months p 0 01 patients jaundice lower rate radical resection 30 8 stage iii iv gallbladder cancer patients without jaundice 62 2 jaundice group median survival 19 5 4 5 months comparable survival 22 1 3 1months patients without jaundice stages iii iv p 0 05 conclusions jaundice important factor indicating prognosis patients gallbladder carcinoma patients jaundice reached stages iii iv low rate radical resection also results poor prognosis patients therefore increased rate radical resection improve prognosis patients jaundice key words gallbladder cancer radical resection patient survival google scholar","probabilities":0.9799733,"Title":"Correlation Between Jaundice And Prognosis Of Gallbladder Cancer","Abstract":"Background: To explore the correlation between the jaundice and the prognosis of gallbladder cancer. Methods: We retrospectively analyzed 181 patients with gallbladder cancer who were treated at our department from December 2002 to June 2010. Jaundice was found in 91 patients and 90 patients without jaundice. Results: The median survival time in patients with jaundice (8.8 \u0001 1.6 months) was significantly shorter than that in one without jaundice (24.8 \u0001 3.0 months) (p < 0.01). All patients with jaundice had stage III or IV gallbladder cancer of whom the median survival time was shorter than that in stage III or IV gallbladder cancer patients without jaundice (16.3 \u0001 2.3 months) (p < 0.01). The patients with jaundice had a lower rate of radical resection (30.8%) than did stage III or IV gallbladder cancer patients without jaundice (62.2%). The jaundice group’s median survival (19.5 \u0001 4.5 months) was comparable to the survival (22.1 \u0001 3.1months) of in-patients without jaundice in stages III & IV (P > 0.05). Conclusions: Jaundice is an important factor indicating the prognosis of patients with gallbladder carcinoma. Most patients with jaundice have reached stages III & IV, and the low rate of radical resection also results in the poor prognosis of these patients. Therefore; an increased rate of radical resection should improve the prognosis of patients with jaundice. Key words: Gallbladder cancer; Radical resection; Patient survival","Source":"Google Scholar","category":"HUMAN","training_data":"Correlation Between Jaundice And Prognosis Of Gallbladder Cancer Background: To explore the correlation between the jaundice and the prognosis of gallbladder cancer. Methods: We retrospectively analyzed 181 patients with gallbladder cancer who were treated at our department from December 2002 to June 2010. Jaundice was found in 91 patients and 90 patients without jaundice. Results: The median survival time in patients with jaundice (8.8 \u0001 1.6 months) was significantly shorter than that in one without jaundice (24.8 \u0001 3.0 months) (p < 0.01). All patients with jaundice had stage III or IV gallbladder cancer of whom the median survival time was shorter than that in stage III or IV gallbladder cancer patients without jaundice (16.3 \u0001 2.3 months) (p < 0.01). The patients with jaundice had a lower rate of radical resection (30.8%) than did stage III or IV gallbladder cancer patients without jaundice (62.2%). The jaundice group’s median survival (19.5 \u0001 4.5 months) was comparable to the survival (22.1 \u0001 3.1months) of in-patients without jaundice in stages III & IV (P > 0.05). Conclusions: Jaundice is an important factor indicating the prognosis of patients with gallbladder carcinoma. Most patients with jaundice have reached stages III & IV, and the low rate of radical resection also results in the poor prognosis of these patients. Therefore; an increased rate of radical resection should improve the prognosis of patients with jaundice. Key words: Gallbladder cancer; Radical resection; Patient survival Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors overall survival advanced intrahepatic cholangiocarcinoma treated yttrium 90 radioembolization abstract purpose evaluate factors associated survival following transarterial 90y yttrium radioembolization tare patients advanced intrahepatic cholangiocarcinoma icc methods retrospective multicenter study analyzed outcome three tertiary care cancer centers patients advanced icc following resin microsphere tare patients included either failed previous anticancer therapy including relapse surgical resection minimum 25 total liver volume ected icc patients stratified response assessed response evaluation criteria solid tumors recist criteria 3 months kaplan meier analysis performed analyze survival followed cox regression determine independent prognostic factors survival results 46 patients included 19 male 27 female median age 62 5 years range 29 88 years total 65 patients undergone previous therapy 63 tumor volume 25 entire liver volume median survival 9 5 months 95 ci 6 1 12 9 months due loss follow n 37 patients included survival analysis cox regression revealed extent liver disease one liver lobes associated survival irrespective tumor volume p 0 041 patients previous surgical resection icc significantly decreased survival 3 9 vs 12 8 months p 0 002 case radiation induced liver disease observed discussion survival 90y tare patients advanced icc primarily depends disease extent limited prognostic factors associated general poor overall survival google scholar","probabilities":0.9799733,"Title":"Prognostic Factors For Overall Survival In Advanced Intrahepatic Cholangiocarcinoma Treated With Yttrium-90 Radioembolization","Abstract":"Abstract: Purpose: To evaluate factors associated with survival following transarterial 90Y (yttrium)\nradioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods:\nThis retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in\npatients with advanced ICC following resin microsphere TARE. Patients were included either after\nfailed previous anticancer therapy, including relapse after surgical resection, or for having a minimum\nof 25% of total liver volume a\u000bected by ICC. Patients were stratified and response was assessed\nby the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan–Meier\nanalysis was performed to analyze survival followed by cox regression to determine independent\nprognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age\n62.5 years (range 29–88 years). A total of 65% of patients had undergone previous therapy, while\n63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI:\n6.1–12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis.\nCox regression revealed the extent of liver disease to one or both liver lobes being associated with\nsurvival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC\nhad significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced\nliver disease was observed. Discussion: Survival after 90Y TARE in patients with advanced ICC\nprimarily depends on disease extent. Only limited prognostic factors are associated with a general\npoor overall survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Factors For Overall Survival In Advanced Intrahepatic Cholangiocarcinoma Treated With Yttrium-90 Radioembolization Abstract: Purpose: To evaluate factors associated with survival following transarterial 90Y (yttrium)\nradioembolization (TARE) in patients with advanced intrahepatic cholangiocarcinoma (ICC). Methods:\nThis retrospective multicenter study analyzed the outcome of three tertiary care cancer centers in\npatients with advanced ICC following resin microsphere TARE. Patients were included either after\nfailed previous anticancer therapy, including relapse after surgical resection, or for having a minimum\nof 25% of total liver volume a\u000bected by ICC. Patients were stratified and response was assessed\nby the Response Evaluation Criteria in Solid Tumors (RECIST) criteria at 3 months. Kaplan–Meier\nanalysis was performed to analyze survival followed by cox regression to determine independent\nprognostic factors for survival. Results: 46 patients were included (19 male, 27 female), median age\n62.5 years (range 29–88 years). A total of 65% of patients had undergone previous therapy, while\n63% had a tumor volume > 25% of the entire liver volume. Median survival was 9.5 months (95% CI:\n6.1–12.9 months). Due to loss in follow-up, n = 37 patients were included in the survival analysis.\nCox regression revealed the extent of liver disease to one or both liver lobes being associated with\nsurvival, irrespective of tumor volume (p = 0.041). Patients with previous surgical resection of ICC\nhad significantly decreased survival (3.9 vs. 12.8 months, p = 0.002). No case of radiation-induced\nliver disease was observed. Discussion: Survival after 90Y TARE in patients with advanced ICC\nprimarily depends on disease extent. Only limited prognostic factors are associated with a general\npoor overall survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder carcinoma utility histopathological evaluation routine cholecystectomy specimens background incidental gallbladder carcinoma igbc rare cancer diagnosed cholecystectomy done benign gallbladder disease concern whether routine histopathological examination needed cholecystectomy specimens still remains debatable materials methods twenty patients diagnosed igbc period 2 years retrospectively reviewed clinical details including clinical presentation preoperative ultrasound usg findings macroscopic features retrieved diagnosis igbc confirmed microscopic examination staging done using tumor node metastasis staging system results 4800 cholecystectomy specimens retrieved diagnosis igbc rendered twenty cases 0 41 mean patient age 50 65 years female preponderance preoperative usg detected increase wall thickness six cases 30 contrast gross examination revealed 55 11 20 cases mucosal ulceration observed two cases 10 igbc seven cases 35 reveal preoperative macroscopic findings suggestive malignancy associated cholelithiasis observed 14 cases final diagnosis igbc made histomorphological assessment tumor cells infiltrating lamina propria three cases pt1b muscularis propria 15 cases pt1b serosa remaining 2 cases pt2 conclusion igbc clinical masquerader often evades eye radiologist comes pathological surprise histopathological examination cholecystectomy specimens remains gold standard detection occult yet notorious malignancy assessment depth invasion igbc guide management stn","probabilities":0.9799733,"Title":"Incidental Gallbladder Carcinoma: Utility Of Histopathological Evaluation Of Routine Cholecystectomy Specimens","Abstract":"Background: Incidental gallbladder carcinoma (IGBC) is rare cancer diagnosed during or after cholecystectomy done for benign gallbladder disease. The concern whether routine histopathological examination is needed for all cholecystectomy specimens still remains debatable. \r\n\r\n Materials and methods: Twenty patients diagnosed with IGBC over a period of 2 years were retrospectively reviewed. Clinical details including clinical presentation, preoperative ultrasound (USG) findings, and macroscopic features were retrieved. Diagnosis of IGBC was confirmed on microscopic examination, and staging was done using the tumor node metastasis staging system. \r\n\r\n Results: Of the 4800 cholecystectomy specimens retrieved, diagnosis of IGBC was rendered in twenty cases (0.41%). Mean patient age was 50.65 years with a female preponderance. Preoperative USG detected an increase in wall thickness in six cases (30%) in contrast to gross examination which revealed the same in 55% (11/20) cases. Mucosal ulceration was observed in two cases (10%) of IGBC and seven cases (35%) did not reveal any preoperative or macroscopic findings suggestive of malignancy. Associated cholelithiasis was observed in 14 cases. Final diagnosis of IGBC was made on histomorphological assessment with tumor cells infiltrating the lamina propria in three cases (pT1b), muscularis propria in 15 cases (pT1b), and serosa in the remaining 2 cases (pT2). \r\n\r\n Conclusion: IGBC is a clinical masquerader which often evades the eye of a radiologist and comes as pathological surprise. Histopathological examination of cholecystectomy specimens remains the gold standard for the detection of this occult, yet notorious malignancy and assessment of the depth of invasion in IGBC guide further management.","Source":"STN","category":"HUMAN","training_data":"Incidental Gallbladder Carcinoma: Utility Of Histopathological Evaluation Of Routine Cholecystectomy Specimens Background: Incidental gallbladder carcinoma (IGBC) is rare cancer diagnosed during or after cholecystectomy done for benign gallbladder disease. The concern whether routine histopathological examination is needed for all cholecystectomy specimens still remains debatable. \r\n\r\n Materials and methods: Twenty patients diagnosed with IGBC over a period of 2 years were retrospectively reviewed. Clinical details including clinical presentation, preoperative ultrasound (USG) findings, and macroscopic features were retrieved. Diagnosis of IGBC was confirmed on microscopic examination, and staging was done using the tumor node metastasis staging system. \r\n\r\n Results: Of the 4800 cholecystectomy specimens retrieved, diagnosis of IGBC was rendered in twenty cases (0.41%). Mean patient age was 50.65 years with a female preponderance. Preoperative USG detected an increase in wall thickness in six cases (30%) in contrast to gross examination which revealed the same in 55% (11/20) cases. Mucosal ulceration was observed in two cases (10%) of IGBC and seven cases (35%) did not reveal any preoperative or macroscopic findings suggestive of malignancy. Associated cholelithiasis was observed in 14 cases. Final diagnosis of IGBC was made on histomorphological assessment with tumor cells infiltrating the lamina propria in three cases (pT1b), muscularis propria in 15 cases (pT1b), and serosa in the remaining 2 cases (pT2). \r\n\r\n Conclusion: IGBC is a clinical masquerader which often evades the eye of a radiologist and comes as pathological surprise. Histopathological examination of cholecystectomy specimens remains the gold standard for the detection of this occult, yet notorious malignancy and assessment of the depth of invasion in IGBC guide further management. STN","prediction_labels":"HUMAN"},{"cleaned":"transarterial chemoembolization tace improved survival unresectable intrahepatic cholangiocarcinoma background patients unresectable intrahepatic cholangio carcinoma icc poor prognosis tace shown prolong survival hepatocellular carcinoma patients ever benefit tace palliative treatment icc unclear aims aims 1 compare survival rates icc patients tace received treatment controls 2 evaluate tumor responses tace treatment 3 evaluate factors affecting outcomes tace treatment methods 563 patients icc diagnosed mayo clinic rochester mn 2000 2009 32 patients unresectable icc received tace identified controls matched patients sex age medical records retrospec tively reviewed survival calculated kaplan meier method tumor responses evaluated modified recist criteria percentage tumor necrosis results icc patients treated tace significantly better survival controls median survival 324 days vs 119 days p 0 01 one two year survival rate 46 9 vs 21 9 p 0 02 18 8 vs 3 1 p 0 01 tace control groups respectively 83 tumor nodules evaluated response tace size tumor stable 59 71 1 decreased 17 20 5 nodules tumor necro sis decrease vascularity found 40 48 2 nodules among 90 necrosis 90 decrease vascularity found 26 31 3 nodules tace group univariate analysis ca 19 9 level 500 calcium level 12 ecog performance status 1 meld 10 significantly associated poor survival p 0 01 multivariate analysis ca 19 9 level hr 9 7 95 ci 2 8 33 4 ecog status hr 5 5 95 ci 1 8 16 5 significant predictors poor outcome p 0 01 conclu sion tace significantly improved survival unresectable icc patients although degrees tumor responses modest prospective studies needed validate results google scholar","probabilities":0.9799733,"Title":"Transarterial Chemoembolization (Tace) Improved Survival In Unresectable Intrahepatic Cholangiocarcinoma","Abstract":"Background: Patients with unresectable intrahepatic cholangio-\ncarcinoma (ICC) have a poor prognosis. TACE has been shown\nto prolong survival in hepatocellular carcinoma patients. How-\never, the benefit of TACE as a palliative treatment for ICC has\nbeen unclear. Aims: Our aims were 1) to compare survival\nrates between ICC patients who had TACE and those who did\nnot received any treatment (controls), 2) to evaluate tumor\nresponses after TACE treatment, and 3) to evaluate factors\naffecting outcomes after TACE treatment. Methods: Of the 563\npatients with ICC diagnosed at Mayo Clinic, Rochester, MN\nfrom 2000-2009, 32 patients with unresectable ICC who\nreceived TACE were identified. Controls were matched to these\npatients by sex and age. All medical records were retrospec-\ntively reviewed. Survival was calculated by the Kaplan-Meier\nmethod. Tumor responses were evaluated by modified RECIST\ncriteria and percentage of tumor necrosis. Results: ICC patients\ntreated with TACE had significantly better survival than controls\n(median survival was 324 days vs 119 days, P = 0.01). The\none- and two-year survival rate was 46.9% vs 21.9% (P =\n0.02) and 18.8% vs 3.1% (P = 0.01) in the TACE and control\ngroups, respectively. Of 83 tumor nodules evaluated for\nresponse to TACE, the size of the tumor was stable in 59\n(71.1%) and decreased in 17 (20.5%) of nodules. Tumor necro-\nsis and a decrease in vascularity was found in 40 (48.2%) nodules. Among these, more than 90% necrosis and more than\n90% decrease in vascularity were found in 26 (31.3%) of all\nnodules. In the TACE group, by univariate analysis, CA 19-9\nlevel ≥ 500, calcium level ≥ 12, ECOG performance status ≥ 1\nand MELD ≥ 10 were significantly associated with poor survival\n(P<0.01). By multivariate analysis, CA 19-9 level (HR 9.7, 95%\nCI 2.8-33.4), and ECOG status (HR 5.5, 95% CI 1.8-16.5)\nwere significant predictors of poor outcome (P<0.01. Conclu-\nsion: TACE significantly improved survival in unresectable ICC\npatients although degrees of tumor responses were modest.\nProspective studies are needed to validate these results.","Source":"Google Scholar","category":"HUMAN","training_data":"Transarterial Chemoembolization (Tace) Improved Survival In Unresectable Intrahepatic Cholangiocarcinoma Background: Patients with unresectable intrahepatic cholangio-\ncarcinoma (ICC) have a poor prognosis. TACE has been shown\nto prolong survival in hepatocellular carcinoma patients. How-\never, the benefit of TACE as a palliative treatment for ICC has\nbeen unclear. Aims: Our aims were 1) to compare survival\nrates between ICC patients who had TACE and those who did\nnot received any treatment (controls), 2) to evaluate tumor\nresponses after TACE treatment, and 3) to evaluate factors\naffecting outcomes after TACE treatment. Methods: Of the 563\npatients with ICC diagnosed at Mayo Clinic, Rochester, MN\nfrom 2000-2009, 32 patients with unresectable ICC who\nreceived TACE were identified. Controls were matched to these\npatients by sex and age. All medical records were retrospec-\ntively reviewed. Survival was calculated by the Kaplan-Meier\nmethod. Tumor responses were evaluated by modified RECIST\ncriteria and percentage of tumor necrosis. Results: ICC patients\ntreated with TACE had significantly better survival than controls\n(median survival was 324 days vs 119 days, P = 0.01). The\none- and two-year survival rate was 46.9% vs 21.9% (P =\n0.02) and 18.8% vs 3.1% (P = 0.01) in the TACE and control\ngroups, respectively. Of 83 tumor nodules evaluated for\nresponse to TACE, the size of the tumor was stable in 59\n(71.1%) and decreased in 17 (20.5%) of nodules. Tumor necro-\nsis and a decrease in vascularity was found in 40 (48.2%) nodules. Among these, more than 90% necrosis and more than\n90% decrease in vascularity were found in 26 (31.3%) of all\nnodules. In the TACE group, by univariate analysis, CA 19-9\nlevel ≥ 500, calcium level ≥ 12, ECOG performance status ≥ 1\nand MELD ≥ 10 were significantly associated with poor survival\n(P<0.01). By multivariate analysis, CA 19-9 level (HR 9.7, 95%\nCI 2.8-33.4), and ECOG status (HR 5.5, 95% CI 1.8-16.5)\nwere significant predictors of poor outcome (P<0.01. Conclu-\nsion: TACE significantly improved survival in unresectable ICC\npatients although degrees of tumor responses were modest.\nProspective studies are needed to validate these results. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance lymph node ratio surgical patients distal cholangiocarcinoma background aim study compare prognostic impact lymph node ratio lnr versus positive lymph node count plnc patients undergone resection distal cholangiocarcinoma methods identified 448 patients resected distal cholangiocarcinoma surveillance epidemiology end results database x tile program used calculate cutoff values lnr plnc discriminate survival overall survival cancer specific survival rates calculated relationships clinicopathological factors patient survival assessed using univariate multivariate analyses results optimal cutoff values lnr plnc 0 45 3 respectively univariate analysis revealed tumor size american joint committee cancer stage stage lnr plnc significantly associated prognosis p 0 05 multivariate analysis demonstrated lnr stage tumor size independent prognostic factors cancer specific overall survival whereas plnc subgroup patients positive lymph nodes patients lnr greater 0 45 significantly worse cancer specific survival hazard ratio 2 418 95 confidence interval 1 588 3 682 p 0 001 overall survival hazard ratio 2 149 95 ci 1 421 3 249 p 0 001 lnr 0 45 less conclusions lnr better predictor long term prognosis plnc patients distal cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic Significance of the Lymph Node Ratio in Surgical Patients With Distal Cholangiocarcinoma","Abstract":"BACKGROUND: The aim of this study was to compare the prognostic impact of the lymph node ratio (LNR) versus positive lymph node count (PLNC) in patients who had undergone resection for distal cholangiocarcinoma. METHODS: We identified 448 patients with resected distal cholangiocarcinoma from the Surveillance, Epidemiology, and End Results database. The X-Tile program was used to calculate the cutoff values for the LNR and PLNC that discriminate survival. The overall survival and cancer-specific survival rates were calculated. Relationships between clinicopathological factors and patient survival were assessed using univariate and multivariate analyses. RESULTS: The optimal cutoff values for the LNR and PLNC were 0.45 and 3, respectively. Univariate analysis revealed that tumor size, the American Joint Committee on Cancer stage, T stage, the LNR and PLNC were significantly associated with prognosis (P < 0.05). Multivariate analysis demonstrated that the LNR, T stage, and tumor size were independent prognostic factors for cancer-specific and overall survival, whereas PLNC was not. In the subgroup of patients with positive lymph nodes, patients with an LNR of greater than 0.45 had significantly worse cancer-specific survival (hazard ratio, 2.418; 95% confidence interval, 1.588 to 3.682; P < 0.001) and overall survival (hazard ratio, 2.149; 95% CI, 1.421 to 3.249; P < 0.001) than those with an LNR of 0.45 or less. CONCLUSIONS: The LNR was a better predictor of long-term prognosis than PLNC in patients with distal cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Significance of the Lymph Node Ratio in Surgical Patients With Distal Cholangiocarcinoma BACKGROUND: The aim of this study was to compare the prognostic impact of the lymph node ratio (LNR) versus positive lymph node count (PLNC) in patients who had undergone resection for distal cholangiocarcinoma. METHODS: We identified 448 patients with resected distal cholangiocarcinoma from the Surveillance, Epidemiology, and End Results database. The X-Tile program was used to calculate the cutoff values for the LNR and PLNC that discriminate survival. The overall survival and cancer-specific survival rates were calculated. Relationships between clinicopathological factors and patient survival were assessed using univariate and multivariate analyses. RESULTS: The optimal cutoff values for the LNR and PLNC were 0.45 and 3, respectively. Univariate analysis revealed that tumor size, the American Joint Committee on Cancer stage, T stage, the LNR and PLNC were significantly associated with prognosis (P < 0.05). Multivariate analysis demonstrated that the LNR, T stage, and tumor size were independent prognostic factors for cancer-specific and overall survival, whereas PLNC was not. In the subgroup of patients with positive lymph nodes, patients with an LNR of greater than 0.45 had significantly worse cancer-specific survival (hazard ratio, 2.418; 95% confidence interval, 1.588 to 3.682; P < 0.001) and overall survival (hazard ratio, 2.149; 95% CI, 1.421 to 3.249; P < 0.001) than those with an LNR of 0.45 or less. CONCLUSIONS: The LNR was a better predictor of long-term prognosis than PLNC in patients with distal cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comprehensive analysis dna methylation gene expression profiles cholangiocarcinoma background incidence cholangiocarcinoma cca risen recent years become significant health burden worldwide however mechanisms underlying tumorigenesis progression disease remain largely unknown increasing number studies demonstrated crucial biological functions epigenetic modifications especially dna methylation cca present study aimed identify analyze methylation regulated differentially expressed genes medegs involved cca tumorigenesis progression bioinformatics analysis methods gene expression profiling dataset gse119336 gene methylation profiling dataset gse38860 obtained gene expression omnibus geo database differentially expressed genes degs differentially methylated genes dmgs identified using limma packages r geo2r respectively medegs obtained overlapping degs dmgs functional enrichment analyses genes carried protein protein interaction ppi networks constructed using string visualized cytoscape determine hub genes finally results verified based cancer genome atlas tcga database results identified 98 hypermethylated downregulated genes 93 hypomethylated upregulated genes overlapping degs dmgs genes mainly enriched biological processes cell cycle nuclear division xenobiotic metabolism drug catabolism negative regulation proteolysis top nine hub genes ppi network f2 ahsg rrm2 aurkb ccna2 top2a birc5 plk1 aspm moreover expression methylation status hub genes significantly altered tcga conclusions study identified novel methylation regulated differentially expressed genes medegs explored related pathways functions cca may provide novel insights understanding methylation mediated regulatory mechanisms cca google scholar","probabilities":0.9467213,"Title":"Comprehensive Analysis Of Dna Methylation And Gene Expression Profiles In Cholangiocarcinoma","Abstract":"Background\nThe incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis.\nMethods\nThe gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein–protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database.\nResults\nWe identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA.\nConclusions\nOur study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA.","Source":"Google Scholar","category":"ANIMAL","training_data":"Comprehensive Analysis Of Dna Methylation And Gene Expression Profiles In Cholangiocarcinoma Background\nThe incidence of cholangiocarcinoma (CCA) has risen in recent years, and it has become a significant health burden worldwide. However, the mechanisms underlying tumorigenesis and progression of this disease remain largely unknown. An increasing number of studies have demonstrated crucial biological functions of epigenetic modifications, especially DNA methylation, in CCA. The present study aimed to identify and analyze methylation-regulated differentially expressed genes (MeDEGs) involved in CCA tumorigenesis and progression by bioinformatics analysis.\nMethods\nThe gene expression profiling dataset (GSE119336) and gene methylation profiling dataset (GSE38860) were obtained from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) and differentially methylated genes (DMGs) were identified using the limma packages of R and GEO2R, respectively. The MeDEGs were obtained by overlapping the DEGs and DMGs. Functional enrichment analyses of these genes were then carried out. Protein–protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape to determine hub genes. Finally, the results were verified based on The Cancer Genome Atlas (TCGA) database.\nResults\nWe identified 98 hypermethylated, downregulated genes and 93 hypomethylated, upregulated genes after overlapping the DEGs and DMGs. These genes were mainly enriched in the biological processes of the cell cycle, nuclear division, xenobiotic metabolism, drug catabolism, and negative regulation of proteolysis. The top nine hub genes of the PPI network were F2, AHSG, RRM2, AURKB, CCNA2, TOP2A, BIRC5, PLK1, and ASPM. Moreover, the expression and methylation status of the hub genes were significantly altered in TCGA.\nConclusions\nOur study identified novel methylation-regulated differentially expressed genes (MeDEGs) and explored their related pathways and functions in CCA, which may provide novel insights into a further understanding of methylation-mediated regulatory mechanisms in CCA. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"pulmonary metastasis resection cholangiocarcinoma incidence resectability survival background reports pulmonary metastasis cholangiocarcinoma therefore incidence resectability survival unclear methods patients underwent surgical resection cholangiocarcinoma including intrahepatic perihilar distal cholangiocarcinoma retrospectively reviewed study focused patients pulmonary metastasis results january 2003 december 2014 681 patients underwent surgical resection cholangiocarcinoma 407 patients experienced disease recurrence including 46 11 3 developed pulmonary metastasis 46 patients 9 underwent resection pulmonary metastasis resection performed remaining 37 patients r0 resection achieved patients complications related pulmonary metastasectomy observed median time recurrence significantly longer 9 patients underwent surgery 37 patients without surgery 2 5 vs 1 0 years p 0 010 survival surgery primary cancer survival recurrence significantly better former group latter group primary cancer 66 7 vs 0 5 years p 0 001 recurrence 40 0 vs 8 7 3 years p 0 003 multivariate analysis identified time recurrence resection pulmonary metastasis independent prognostic factors survival recurrence conclusion resection pulmonary metastasis originating cholangiocarcinoma safely performed confers survival benefits select patients especially longer time recurrence initial surgery pubmed","probabilities":0.9799733,"Title":"Pulmonary Metastasis After Resection of Cholangiocarcinoma: Incidence, Resectability, and Survival","Abstract":"BACKGROUND: There are few reports on pulmonary metastasis from cholangiocarcinoma; therefore, its incidence, resectability, and survival are unclear. METHODS: Patients who underwent surgical resection for cholangiocarcinoma, including intrahepatic, perihilar, and distal cholangiocarcinoma were retrospectively reviewed, and this study focused on patients with pulmonary metastasis. RESULTS: Between January 2003 and December 2014, 681 patients underwent surgical resection for cholangiocarcinoma. Of these, 407 patients experienced disease recurrence, including 46 (11.3%) who developed pulmonary metastasis. Of these 46 patients, 9 underwent resection for pulmonary metastasis; no resection was performed in the remaining 37 patients. R0 resection was achieved in all patients, and no complications related to pulmonary metastasectomy were observed. The median time to recurrence was significantly longer in the 9 patients who underwent surgery than in the 37 patients without surgery (2.5 vs 1.0 years, p < 0.010). Survival after surgery for primary cancer and survival after recurrence were significantly better in the former group than in the latter group (after primary cancer: 66.7 vs 0% at 5 years, p < 0.001; after recurrence: 40.0 vs 8.7% at 3 years, p = 0.003). Multivariate analysis identified the time to recurrence and resection for pulmonary metastasis as independent prognostic factors for survival after recurrence. CONCLUSION: Resection for pulmonary metastasis originating from cholangiocarcinoma can be safely performed and confers survival benefits for select patients, especially those with a longer time to recurrence after initial surgery.","Source":"PubMed","category":"HUMAN","training_data":"Pulmonary Metastasis After Resection of Cholangiocarcinoma: Incidence, Resectability, and Survival BACKGROUND: There are few reports on pulmonary metastasis from cholangiocarcinoma; therefore, its incidence, resectability, and survival are unclear. METHODS: Patients who underwent surgical resection for cholangiocarcinoma, including intrahepatic, perihilar, and distal cholangiocarcinoma were retrospectively reviewed, and this study focused on patients with pulmonary metastasis. RESULTS: Between January 2003 and December 2014, 681 patients underwent surgical resection for cholangiocarcinoma. Of these, 407 patients experienced disease recurrence, including 46 (11.3%) who developed pulmonary metastasis. Of these 46 patients, 9 underwent resection for pulmonary metastasis; no resection was performed in the remaining 37 patients. R0 resection was achieved in all patients, and no complications related to pulmonary metastasectomy were observed. The median time to recurrence was significantly longer in the 9 patients who underwent surgery than in the 37 patients without surgery (2.5 vs 1.0 years, p < 0.010). Survival after surgery for primary cancer and survival after recurrence were significantly better in the former group than in the latter group (after primary cancer: 66.7 vs 0% at 5 years, p < 0.001; after recurrence: 40.0 vs 8.7% at 3 years, p = 0.003). Multivariate analysis identified the time to recurrence and resection for pulmonary metastasis as independent prognostic factors for survival after recurrence. CONCLUSION: Resection for pulmonary metastasis originating from cholangiocarcinoma can be safely performed and confers survival benefits for select patients, especially those with a longer time to recurrence after initial surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"alcohol gastrointestinal cancers purpose review alcohol type carcinogen stated caused 5 deaths 2016 13 cancers among digestive tract cancers association clear esophageal liver colorectal cancer debated gastric pancreatic cancer present review revise recent evidence epidemiologic association mechanisms linking alcohol risk esophageal gastric colorectal pancreatic cancers recent findings moderate alcohol intake increases risk esophageal squamous cell carcinoma colorectal cancer heavy alcohol intake associated increased risk gastric pancreatic cancers risks also depend genetic variants interaction smoking inconsistent carcinogenic mechanisms multiple key role acetaldehyde ability cause dna damage alter telomere length induce ros data role gut microbiome possible mediator alcohol induced carcinogenesis limited summary sufficient evidence association alcohol consumption cancers esophagus stomach colon rectum pancreas public health policies prevent cancer types include modification alcohol intake habits especially among individuals increased risk pubmed","probabilities":0.962963,"Title":"Alcohol and gastrointestinal cancers","Abstract":"PURPOSE OF REVIEW: Alcohol is a type I carcinogen and the WHO stated that it caused 5% of all deaths in 2016, of which 13% because of cancers. Among digestive tract cancers, this association is clear for esophageal, liver and colorectal cancer, and more debated for gastric and pancreatic cancer. The present review will revise recent evidence on epidemiologic association and mechanisms linking alcohol with the risk of esophageal, gastric, colorectal and pancreatic cancers. RECENT FINDINGS: Moderate alcohol intake increases the risk of esophageal squamous cell carcinoma and colorectal cancer. Heavy alcohol intake is associated with an increased risk of gastric and pancreatic cancers. These risks also depend on genetic variants and the interaction with smoking is inconsistent. The carcinogenic mechanisms are multiple with a key role of acetaldehyde because of its ability to cause DNA damage, alter telomere length and induce ROS. Data on the role of the gut microbiome as possible mediator of alcohol-induced carcinogenesis are limited. SUMMARY: There is sufficient evidence for the association between alcohol consumption and cancers of the esophagus, stomach, colon-rectum and pancreas. Public health policies to prevent these cancer types should include modification of alcohol intake habits, especially among individuals at increased risk.","Source":"PubMed","category":"HUMAN","training_data":"Alcohol and gastrointestinal cancers PURPOSE OF REVIEW: Alcohol is a type I carcinogen and the WHO stated that it caused 5% of all deaths in 2016, of which 13% because of cancers. Among digestive tract cancers, this association is clear for esophageal, liver and colorectal cancer, and more debated for gastric and pancreatic cancer. The present review will revise recent evidence on epidemiologic association and mechanisms linking alcohol with the risk of esophageal, gastric, colorectal and pancreatic cancers. RECENT FINDINGS: Moderate alcohol intake increases the risk of esophageal squamous cell carcinoma and colorectal cancer. Heavy alcohol intake is associated with an increased risk of gastric and pancreatic cancers. These risks also depend on genetic variants and the interaction with smoking is inconsistent. The carcinogenic mechanisms are multiple with a key role of acetaldehyde because of its ability to cause DNA damage, alter telomere length and induce ROS. Data on the role of the gut microbiome as possible mediator of alcohol-induced carcinogenesis are limited. SUMMARY: There is sufficient evidence for the association between alcohol consumption and cancers of the esophagus, stomach, colon-rectum and pancreas. Public health policies to prevent these cancer types should include modification of alcohol intake habits, especially among individuals at increased risk. PubMed","prediction_labels":"HUMAN"},{"cleaned":"reduced expression raf 1 kinase inhibitory protein significant prognostic marker patients gallbladder carcinoma gallbladder carcinoma one aggressive malignancies usually diagnosed advanced stage prognosis remains poor despite advances imaging techniques aggressive surgical treatment lack reliable prognostic markers aim study investigate prognostic significance raf 1 kinase inhibitory protein expression gallbladder carcinomas immunostaining raf 1 kinase inhibitory protein performed chronic cholecystitis adenoma carcinoma situ primary nodal metastatic gallbladder carcinoma raf 1 kinase inhibitory protein expression reduced 68 8 11 16 42 3 44 104 nodal metastatic primary gallbladder carcinoma cases respectively case carcinoma situ adenoma chronic cholecystitis differences raf 1 kinase inhibitory protein expression gallbladder carcinoma versus nongallbladder carcinoma tissues p 001 nodal metastatic gallbladder carcinoma versus primary gallbladder carcinoma p 009 statistically significant kaplan meier curves showed patients raf 1 kinase inhibitory protein negative weakly positive gallbladder carcinoma significantly shorter overall survival patients raf 1 kinase inhibitory protein positive gallbladder carcinoma median 14 versus 120 months p 011 multivariate survival analysis showed reduced raf 1 kinase inhibitory protein expression independent prognostic predictor overall survival p 020 results suggest reduction raf 1 kinase inhibitory protein expression gallbladder carcinoma contributes invasion metastasis significant prognostic marker patients gallbladder carcinoma stn","probabilities":0.88235295,"Title":"Reduced Expression Of Raf-1 Kinase Inhibitory Protein Is A Significant Prognostic Marker In Patients With Gallbladder Carcinoma","Abstract":"Gallbladder carcinoma is one of the most aggressive malignancies. It is usually diagnosed at an advanced stage, and the prognosis remains poor despite advances in imaging techniques and aggressive surgical treatment. Because of the lack of reliable prognostic markers, the aim of this study was to investigate the prognostic significance of Raf-1 kinase inhibitory protein expression in gallbladder carcinomas. Immunostaining for Raf-1 kinase inhibitory protein was performed on chronic cholecystitis, adenoma, carcinoma in situ, and primary and nodal metastatic gallbladder carcinoma. Raf-1 kinase inhibitory protein expression was reduced in 68.8% (11/16) and 42.3% (44/104) of nodal metastatic and primary gallbladder carcinoma cases, respectively, but in no case of carcinoma in situ, adenoma, or chronic cholecystitis. The differences in Raf-1 kinase inhibitory protein expression in gallbladder carcinoma versus nongallbladder carcinoma tissues (P < .001), and in nodal metastatic gallbladder carcinoma versus primary gallbladder carcinoma (P = .009), were statistically significant. Kaplan-Meier curves showed that patients with Raf-1 kinase inhibitory protein-negative or weakly positive gallbladder carcinoma had a significantly shorter overall survival than did patients with Raf-1 kinase inhibitory protein-positive gallbladder carcinoma (median, 14 versus 120 months; P = .011). Multivariate survival analysis showed that reduced Raf-1 kinase inhibitory protein expression was an independent prognostic predictor for overall survival (P = .020). Our results suggest that reduction in Raf-1 kinase inhibitory protein expression in gallbladder carcinoma contributes to invasion and metastasis and is a significant prognostic marker in patients with gallbladder carcinoma.","Source":"STN","category":"HUMAN","training_data":"Reduced Expression Of Raf-1 Kinase Inhibitory Protein Is A Significant Prognostic Marker In Patients With Gallbladder Carcinoma Gallbladder carcinoma is one of the most aggressive malignancies. It is usually diagnosed at an advanced stage, and the prognosis remains poor despite advances in imaging techniques and aggressive surgical treatment. Because of the lack of reliable prognostic markers, the aim of this study was to investigate the prognostic significance of Raf-1 kinase inhibitory protein expression in gallbladder carcinomas. Immunostaining for Raf-1 kinase inhibitory protein was performed on chronic cholecystitis, adenoma, carcinoma in situ, and primary and nodal metastatic gallbladder carcinoma. Raf-1 kinase inhibitory protein expression was reduced in 68.8% (11/16) and 42.3% (44/104) of nodal metastatic and primary gallbladder carcinoma cases, respectively, but in no case of carcinoma in situ, adenoma, or chronic cholecystitis. The differences in Raf-1 kinase inhibitory protein expression in gallbladder carcinoma versus nongallbladder carcinoma tissues (P < .001), and in nodal metastatic gallbladder carcinoma versus primary gallbladder carcinoma (P = .009), were statistically significant. Kaplan-Meier curves showed that patients with Raf-1 kinase inhibitory protein-negative or weakly positive gallbladder carcinoma had a significantly shorter overall survival than did patients with Raf-1 kinase inhibitory protein-positive gallbladder carcinoma (median, 14 versus 120 months; P = .011). Multivariate survival analysis showed that reduced Raf-1 kinase inhibitory protein expression was an independent prognostic predictor for overall survival (P = .020). Our results suggest that reduction in Raf-1 kinase inhibitory protein expression in gallbladder carcinoma contributes to invasion and metastasis and is a significant prognostic marker in patients with gallbladder carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"incidence mortality trends biliary tract cancers austria background aims epidemiology biliary tract cancers btc varies geographical regions changed time globally investigated incidence mortality trends patients diagnosed btc 20 year period austria methods patients diagnosed intrahepatic iccc extrahepatic cholangiocarcinoma eccc ampullary carcinoma gall bladder carcinoma gbc overlapping lesions unspecified carcinomas biliary tract liver included data age adjusted incidence obtained austrian national cancer registry compiles data newly diagnosed cancers data age adjusted mortality obtained national death registry statistics austria results 1990 2009 15201 patients diagnosed btc m f 42 58 mean age 73 years median survival patients btc 4 8 months 1 5 year survival rate 31 10 iccc incidence mortality rates increased 1990 2009 men women eccc incidence mortality rates decreased time sexes ampullary carcinoma incidence slightly decreased men remained stable women mortality rate remained stable sexes gbc age adjusted incidence mortality rates dramatically decreased sexes conclusions gbc iccc common entities amongst btc incidence mortality rates iccc increased men women time incidence mortality rates eccc gbc decreased sexes carcinomas biliary tract e ampullary carcinoma rarely diagnosed stn","probabilities":0.9799733,"Title":"Incidence And Mortality Trends For Biliary Tract Cancers In Austria","Abstract":"Background & aims: The epidemiology of biliary tract cancers (BTC) varies between geographical regions and has changed over time globally. We investigated the incidence and mortality trends of patients diagnosed with BTC over a 20-year period in Austria. \r\n\r\n Methods: Patients diagnosed with intrahepatic (iCCC)/extrahepatic cholangiocarcinoma (eCCC), ampullary carcinoma, gall bladder carcinoma (GBC), overlapping lesions or unspecified carcinomas of the biliary tract and liver were included. Data on age-adjusted incidence were obtained from the Austrian National Cancer Registry which compiles data on all newly diagnosed cancers. Data on age-adjusted mortality were obtained from the national death registry (Statistics Austria). \r\n\r\n Results: Between 1990 and 2009, 15201 patients were diagnosed with BTC (m/f=42/58%; mean age, 73 years). The median survival of all patients with BTC was 4.8 months with a 1-/5-year survival rate of 31%/10%. In iCCC, the incidence and mortality rates increased from 1990 to 2009 in both men and women while in eCCC, the incidence and mortality rates decreased over time in both sexes. In ampullary carcinoma, the incidence slightly decreased in men and remained stable in women. The mortality rate remained stable in both sexes. In GBC, the age-adjusted incidence and mortality rates dramatically decreased in both sexes. \r\n\r\n Conclusions: GBC and iCCC were the most common entities amongst BTC. While incidence and mortality rates of iCCC increased in men and women over time, incidence and mortality rates of eCCC and GBC decreased in both sexes. Other carcinomas of the biliary tract i.e. ampullary carcinoma were rarely diagnosed.","Source":"STN","category":"HUMAN","training_data":"Incidence And Mortality Trends For Biliary Tract Cancers In Austria Background & aims: The epidemiology of biliary tract cancers (BTC) varies between geographical regions and has changed over time globally. We investigated the incidence and mortality trends of patients diagnosed with BTC over a 20-year period in Austria. \r\n\r\n Methods: Patients diagnosed with intrahepatic (iCCC)/extrahepatic cholangiocarcinoma (eCCC), ampullary carcinoma, gall bladder carcinoma (GBC), overlapping lesions or unspecified carcinomas of the biliary tract and liver were included. Data on age-adjusted incidence were obtained from the Austrian National Cancer Registry which compiles data on all newly diagnosed cancers. Data on age-adjusted mortality were obtained from the national death registry (Statistics Austria). \r\n\r\n Results: Between 1990 and 2009, 15201 patients were diagnosed with BTC (m/f=42/58%; mean age, 73 years). The median survival of all patients with BTC was 4.8 months with a 1-/5-year survival rate of 31%/10%. In iCCC, the incidence and mortality rates increased from 1990 to 2009 in both men and women while in eCCC, the incidence and mortality rates decreased over time in both sexes. In ampullary carcinoma, the incidence slightly decreased in men and remained stable in women. The mortality rate remained stable in both sexes. In GBC, the age-adjusted incidence and mortality rates dramatically decreased in both sexes. \r\n\r\n Conclusions: GBC and iCCC were the most common entities amongst BTC. While incidence and mortality rates of iCCC increased in men and women over time, incidence and mortality rates of eCCC and GBC decreased in both sexes. Other carcinomas of the biliary tract i.e. ampullary carcinoma were rarely diagnosed. STN","prediction_labels":"HUMAN"},{"cleaned":"longterm outcome photodynamic therapy compared biliary stenting alone patients advanced hilar cholangiocarcinoma objectives study aimed determine longterm outcomes factors associated increased survival photodynamic therapy pdt compared endoscopic biliary drainage alone patients presenting advanced hilar cholangiocarcinoma cc methods retrospective analysis institutional database identifying patients presented diagnosis hilar cc december 1999 january 2011 conducted results 232 patients identified 72 31 treated pdt group 71 31 treated endoscopic biliary drainage alone group b median survival 9 8 months 95 confidence interval ci 7 42 12 25 group 7 3 months 95 ci 4 79 9 88 group b p 0 029 multivariate analysis biliary drainage without pdt p 0 025 higher stage p 0 002 significant predictors shorter survival patients subgroup analysis patients pdt group lower pre pdt bilirubin level p 0 005 multiple pdt treatments p 0 044 shortened time treatment diagnosis p 0 013 significant predictors improved survival median metal stent patency longer group group b 215 days vs 181 days p 0 018 conclusions photodynamic therapy stenting resulted longer survival stenting alone early pdt diagnosis multiple pdt treatments shown survival benefits metal stent patency longer patients receiving pdt higher stage appears predictor early mortality advanced bile duct cancer treated pdt pubmed","probabilities":0.9799733,"Title":"Longterm outcome of photodynamic therapy compared with biliary stenting alone in patients with advanced hilar cholangiocarcinoma","Abstract":"OBJECTIVES: This study aimed to determine longterm outcomes and factors associated with increased survival after photodynamic therapy (PDT) compared with endoscopic biliary drainage alone in patients presenting with advanced hilar cholangiocarcinoma (CC). METHODS: A retrospective analysis of the institutional database identifying all patients who presented with a diagnosis of hilar CC between December 1999 and January 2011 was conducted. RESULTS: Of the 232 patients identified, 72 (31%) were treated with PDT (Group A) and 71 (31%) were treated with endoscopic biliary drainage alone (Group B). Median survival was 9.8 months [95% confidence interval (CI) 7.42-12.25] in Group A and 7.3 months (95% CI 4.79-9.88) in Group B (P= 0.029). On multivariate analysis, biliary drainage without PDT (P= 0.025) and higher T-stage (P= 0.002) were significant predictors of shorter survival in all patients. In a subgroup analysis of patients in the PDT group, lower pre-PDT bilirubin level (P= 0.005), multiple PDT treatments (P= 0.044) and shortened time to treatment after diagnosis (P= 0.013) were significant predictors of improved survival. Median metal stent patency was longer in Group A than in Group B (215 days vs. 181 days; P= 0.018). CONCLUSIONS: Photodynamic therapy with stenting resulted in longer survival than stenting alone. Early PDT after diagnosis and multiple PDT treatments were shown to have survival benefits. Metal stent patency was longer in patients receiving PDT. Higher T-stage appears to be a predictor of early mortality in advanced bile duct cancer treated with PDT.","Source":"PubMed","category":"HUMAN","training_data":"Longterm outcome of photodynamic therapy compared with biliary stenting alone in patients with advanced hilar cholangiocarcinoma OBJECTIVES: This study aimed to determine longterm outcomes and factors associated with increased survival after photodynamic therapy (PDT) compared with endoscopic biliary drainage alone in patients presenting with advanced hilar cholangiocarcinoma (CC). METHODS: A retrospective analysis of the institutional database identifying all patients who presented with a diagnosis of hilar CC between December 1999 and January 2011 was conducted. RESULTS: Of the 232 patients identified, 72 (31%) were treated with PDT (Group A) and 71 (31%) were treated with endoscopic biliary drainage alone (Group B). Median survival was 9.8 months [95% confidence interval (CI) 7.42-12.25] in Group A and 7.3 months (95% CI 4.79-9.88) in Group B (P= 0.029). On multivariate analysis, biliary drainage without PDT (P= 0.025) and higher T-stage (P= 0.002) were significant predictors of shorter survival in all patients. In a subgroup analysis of patients in the PDT group, lower pre-PDT bilirubin level (P= 0.005), multiple PDT treatments (P= 0.044) and shortened time to treatment after diagnosis (P= 0.013) were significant predictors of improved survival. Median metal stent patency was longer in Group A than in Group B (215 days vs. 181 days; P= 0.018). CONCLUSIONS: Photodynamic therapy with stenting resulted in longer survival than stenting alone. Early PDT after diagnosis and multiple PDT treatments were shown to have survival benefits. Metal stent patency was longer in patients receiving PDT. Higher T-stage appears to be a predictor of early mortality in advanced bile duct cancer treated with PDT. PubMed","prediction_labels":"HUMAN"},{"cleaned":"primary gallbladder cancer discovered postoperatively elective emergency cholecystectomy background gallbladder cancer rare neoplasm associated high mortality poor prognosis usually correlated cholelithiasis presents commonly elderly female patients diagnosis seldom made preoperatively indolent progression tumor methods hospitalization surgical records surgical department examined january 1992 december 2001 searching patients undergone cholecystectomy additionally histopathological diagnoses period studied searching patients diagnosis gallbladder cancer established post operatively intraoperatively frozen section results period 1992 2001 total 1 536 cholecystectomies took place 14 cases gallbladder cancer diagnosed postoperatively ratio men women 3 11 mean age 69 4 years clinical symptoms nonspecific mortality 57 conclusion cases gallbladder cancer diagnosed cholecystectomy even cases advanced stage prognosis rare neoplasm poor stn","probabilities":0.9799733,"Title":"Primary Gallbladder Cancer Discovered Postoperatively After Elective And Emergency Cholecystectomy","Abstract":"Background: Gallbladder cancer is a rare neoplasm associated with high mortality and poor prognosis. It is usually correlated with cholelithiasis and presents more commonly in elderly and female patients. Diagnosis is seldom made preoperatively because of the indolent progression of the tumor. \r\n\r\n Methods: The hospitalization and surgical records of our surgical department were examined from January 1992 to December 2001, searching for patients who had undergone cholecystectomy. Additionally, the histopathological diagnoses of the same period were studied searching for patients with the diagnosis of gallbladder cancer established post-operatively and not intraoperatively by frozen section. \r\n\r\n Results: In the period of 1992- 2001, a total of 1,536 cholecystectomies took place and 14 cases of gallbladder cancer were diagnosed postoperatively. The ratio of men to women is 3/ 11 with a mean age of 69.4 years. The clinical symptoms were nonspecific and mortality was 57%. \r\n\r\n Conclusion: In most cases gallbladder cancer is diagnosed after cholecystectomy and even in these cases it can be in an advanced stage and the prognosis of this rare neoplasm is poor.","Source":"STN","category":"HUMAN","training_data":"Primary Gallbladder Cancer Discovered Postoperatively After Elective And Emergency Cholecystectomy Background: Gallbladder cancer is a rare neoplasm associated with high mortality and poor prognosis. It is usually correlated with cholelithiasis and presents more commonly in elderly and female patients. Diagnosis is seldom made preoperatively because of the indolent progression of the tumor. \r\n\r\n Methods: The hospitalization and surgical records of our surgical department were examined from January 1992 to December 2001, searching for patients who had undergone cholecystectomy. Additionally, the histopathological diagnoses of the same period were studied searching for patients with the diagnosis of gallbladder cancer established post-operatively and not intraoperatively by frozen section. \r\n\r\n Results: In the period of 1992- 2001, a total of 1,536 cholecystectomies took place and 14 cases of gallbladder cancer were diagnosed postoperatively. The ratio of men to women is 3/ 11 with a mean age of 69.4 years. The clinical symptoms were nonspecific and mortality was 57%. \r\n\r\n Conclusion: In most cases gallbladder cancer is diagnosed after cholecystectomy and even in these cases it can be in an advanced stage and the prognosis of this rare neoplasm is poor. STN","prediction_labels":"HUMAN"},{"cleaned":"pathohistological subtype strongly predicts survival patients ampullary carcinoma ampullary cancer represents approximately 6 malignant periampullary tumors early occurrence symptoms leads 5 year survival rate curative surgery 30 67 addition tumor stage immunohistological subtypes appear important postoperative prognosis aim study analyze different subtypes regarding prognostic relevance total 170 patients ampullary cancer retrospectively analyzed 1999 2016 pancreatic resection patients grouped according pathohistological subtype ampullary cancer pancreatobiliary intestinal mixed characteristics among groups analyzed using univariate multivariate models survival probability analyzed kaplan meier method exact subtyping possible 119 patients pancreatobiliary subtype diagnosed 69 patients 58 intestinal 41 patients 34 5 mixed subtype 9 patients 7 6 survival analysis showed significantly worse 5 year survival rate pancreatobiliary subtype compared intestinal subtype 27 5 versus 61 p 0 001 mean overall survival patients pancreatobiliary intestinal mixed subtype 52 5 115 94 7 months respectively p 0 001 pathohistological subtypes ampullary cancer allows prediction postoperative prognosis stn","probabilities":0.9799733,"Title":"The Pathohistological Subtype Strongly Predicts Survival In Patients With Ampullary Carcinoma","Abstract":"Ampullary cancer represents approximately 6% of the malignant periampullary tumors. An early occurrence of symptoms leads to a 5-year survival rate after curative surgery of 30 to 67%. In addition to the tumor stage, the immunohistological subtypes appear to be important for postoperative prognosis. The aim of this study was to analyze the different subtypes regarding their prognostic relevance. A total of 170 patients with ampullary cancer were retrospectively analyzed between 1999 until 2016 after pancreatic resection. Patients were grouped according to their pathohistological subtype of ampullary cancer (pancreatobiliary, intestinal, mixed). Characteristics among the groups were analyzed using univariate and multivariate models. Survival probability was analyzed by the Kaplan-Meier method. An exact subtyping was possible in 119 patients. A pancreatobiliary subtype was diagnosed in 69 patients (58%), intestinal in 41 patients (34.5%), and a mixed subtype in 9 patients (7.6%). Survival analysis showed a significantly worse 5-year survival rate for the pancreatobiliary subtype compared with the intestinal subtype (27.5% versus 61%, p < 0.001). The mean overall survival of patients with pancreatobiliary, intestinal, and mixed subtype was 52.5, 115 and 94.7 months, respectively (p < 0.001). The pathohistological subtypes of ampullary cancer allows a prediction of the postoperative prognosis.","Source":"STN","category":"HUMAN","training_data":"The Pathohistological Subtype Strongly Predicts Survival In Patients With Ampullary Carcinoma Ampullary cancer represents approximately 6% of the malignant periampullary tumors. An early occurrence of symptoms leads to a 5-year survival rate after curative surgery of 30 to 67%. In addition to the tumor stage, the immunohistological subtypes appear to be important for postoperative prognosis. The aim of this study was to analyze the different subtypes regarding their prognostic relevance. A total of 170 patients with ampullary cancer were retrospectively analyzed between 1999 until 2016 after pancreatic resection. Patients were grouped according to their pathohistological subtype of ampullary cancer (pancreatobiliary, intestinal, mixed). Characteristics among the groups were analyzed using univariate and multivariate models. Survival probability was analyzed by the Kaplan-Meier method. An exact subtyping was possible in 119 patients. A pancreatobiliary subtype was diagnosed in 69 patients (58%), intestinal in 41 patients (34.5%), and a mixed subtype in 9 patients (7.6%). Survival analysis showed a significantly worse 5-year survival rate for the pancreatobiliary subtype compared with the intestinal subtype (27.5% versus 61%, p < 0.001). The mean overall survival of patients with pancreatobiliary, intestinal, and mixed subtype was 52.5, 115 and 94.7 months, respectively (p < 0.001). The pathohistological subtypes of ampullary cancer allows a prediction of the postoperative prognosis. STN","prediction_labels":"HUMAN"},{"cleaned":"evaluation tumor markers impact prognosis gallbladder bile duct cholangiocellular carcinomas pilot study background aim behavior tumor markers biliary tract malignancies well known scarcely studied markers play important roles diagnostic prognostic schemes well decision making best treatment strategies study analyzed preoperative serum levels conventional tumor markers afp cea ca 19 9 ca 72 4 proliferative marker thymidine kinase tk cytokeratins tpa tps cyfra 21 1 patients gallbladder carcinoma bile duct carcinoma klatskin cholangiocellular carcinoma relation patient prognosis study aimed finding role tumor markers properly investigated diseases importance often marginalized materials methods study included 43 patients underwent either radical surgical procedure n 21 explorative laparotomy without surgical treatment n 22 gallbladder carcinoma bile duct carcinoma klatskin tumor cholangiocellular carcinoma 24 8 11 patients respectively 2003 2010 department association serum tumor markers patients prognosis assessed entire cohort cancer type also regard treatment radical surgery versus explorative laparotomy overall survival os disease free interval dfi estimated kaplan meier method statistically evaluated using logrank test dfi computed subgroup patients treated radical surgery results statistical analysis tumor markers revealed tk poor prognostic factor shorter dfi hr 3 5 95 ci 0 6 21 3 p 0 05 also os hr 4 6 95 ci 1 0 4 7 p 0 05 patients gallbladder carcinoma treated radical surgery tps demonstrated poor prognostic factor os patients gallbladder carcinoma hr 12 7 95 ci 1 4 117 7 p 0 05 cea proven factor poor prognosis shorter os patients explorative laparotomy cumulated studied diagnoses hr 9 8 95 ci 1 05 92 7 p 0 05 conclusion results study suggested importance tumor markers assessment prognosis os dfi patients gallbladder carcinoma bile duct carcinoma cholangiocellular carcinoma pubmed","probabilities":0.9799733,"Title":"Evaluation of Tumor Markers and Their Impact on Prognosis in Gallbladder, Bile Duct and Cholangiocellular Carcinomas - A Pilot Study","Abstract":"BACKGROUND/AIM: The behavior of tumor markers in biliary tract malignancies is not well-known and has been scarcely studied. Such markers could play important roles in diagnostic and prognostic schemes as well as in decision-making about the best treatment strategies. This study analyzed the preoperative serum levels of conventional tumor markers (AFP, CEA, CA 19-9, CA 72-4), proliferative marker thymidine kinase (TK) and cytokeratins (TPA, TPS and CYFRA 21.1) in patients with gallbladder carcinoma, bile duct carcinoma (Klatskin) and cholangiocellular carcinoma, in relation to the patient prognosis. The study aimed in finding the role of tumor markers in not properly investigated diseases, where their importance is often marginalized. MATERIALS AND METHODS: The study included 43 patients, who underwent either radical surgical procedure (n=21) or explorative laparotomy without any surgical treatment (n=22) for gallbladder carcinoma, bile duct carcinoma (Klatskin tumor) and cholangiocellular carcinoma (24, 8 and 11 patients, respectively) between 2003 and 2010 at our Department. The association of serum tumor markers and patients' prognosis were assessed for the entire cohort and for each cancer type and also with regard to treatment (radical surgery versus explorative laparotomy). Overall survival (OS) and disease-free interval (DFI) were estimated by the Kaplan-Meier method and statistically evaluated using the LogRank test. DFI was computed only in the subgroup of patients treated by radical surgery. RESULTS: The statistical analysis of tumor markers revealed TK as a poor prognostic factor for shorter DFI (HR=3.5, 95%CI=0.6-21.3, p<0.05) and also OS (HR=4.6, 95%CI=1.0-4.7, p<0.05) in patients with gallbladder carcinoma treated with radical surgery. TPS was demonstrated as a poor prognostic factor for OS in patients with gallbladder carcinoma (HR=12.7, 95%CI=1.4-117.7, p<0.05). CEA was proven to be a factor of poor prognosis with shorter OS in patients after explorative laparotomy for all cumulated studied diagnoses (HR=9.8, 95%CI=1.05-92.7, p<0.05). CONCLUSION: The results of this study suggested the importance of tumor markers for assessment of prognosis (OS or DFI) in patients with gallbladder carcinoma, bile duct carcinoma, and cholangiocellular carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of Tumor Markers and Their Impact on Prognosis in Gallbladder, Bile Duct and Cholangiocellular Carcinomas - A Pilot Study BACKGROUND/AIM: The behavior of tumor markers in biliary tract malignancies is not well-known and has been scarcely studied. Such markers could play important roles in diagnostic and prognostic schemes as well as in decision-making about the best treatment strategies. This study analyzed the preoperative serum levels of conventional tumor markers (AFP, CEA, CA 19-9, CA 72-4), proliferative marker thymidine kinase (TK) and cytokeratins (TPA, TPS and CYFRA 21.1) in patients with gallbladder carcinoma, bile duct carcinoma (Klatskin) and cholangiocellular carcinoma, in relation to the patient prognosis. The study aimed in finding the role of tumor markers in not properly investigated diseases, where their importance is often marginalized. MATERIALS AND METHODS: The study included 43 patients, who underwent either radical surgical procedure (n=21) or explorative laparotomy without any surgical treatment (n=22) for gallbladder carcinoma, bile duct carcinoma (Klatskin tumor) and cholangiocellular carcinoma (24, 8 and 11 patients, respectively) between 2003 and 2010 at our Department. The association of serum tumor markers and patients' prognosis were assessed for the entire cohort and for each cancer type and also with regard to treatment (radical surgery versus explorative laparotomy). Overall survival (OS) and disease-free interval (DFI) were estimated by the Kaplan-Meier method and statistically evaluated using the LogRank test. DFI was computed only in the subgroup of patients treated by radical surgery. RESULTS: The statistical analysis of tumor markers revealed TK as a poor prognostic factor for shorter DFI (HR=3.5, 95%CI=0.6-21.3, p<0.05) and also OS (HR=4.6, 95%CI=1.0-4.7, p<0.05) in patients with gallbladder carcinoma treated with radical surgery. TPS was demonstrated as a poor prognostic factor for OS in patients with gallbladder carcinoma (HR=12.7, 95%CI=1.4-117.7, p<0.05). CEA was proven to be a factor of poor prognosis with shorter OS in patients after explorative laparotomy for all cumulated studied diagnoses (HR=9.8, 95%CI=1.05-92.7, p<0.05). CONCLUSION: The results of this study suggested the importance of tumor markers for assessment of prognosis (OS or DFI) in patients with gallbladder carcinoma, bile duct carcinoma, and cholangiocellular carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiology cholangiocarcinoma cholangiocarcinoma cca cancer arising intra extrahepatic bile ducts mainly characterized late diagnosis fatal outcome cca second common primary liver tumour accounts approximately 10 15 hepatobiliary malignancies development cca linked wide spectrum conditions causing biliary inflammation cholestasis inflammation liver geographic diversity risk factors reflected considerable differences incidence worldwide although data consistent incidence seems rising western world given limited opportunities treating advanced cca surveillance suggested strategy detection early disease high risk group patients primary sclerosing cholangitis psc review present updated overview epidemiology cca also highlight risk cca psc special focus surveillance strategies pubmed","probabilities":0.9799733,"Title":"Epidemiology of cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a cancer arising from the intra- or extrahepatic bile ducts and mainly characterized by its late diagnosis and fatal outcome. CCA is the second most common primary liver tumour and accounts for approximately 10-15% of all hepatobiliary malignancies. The development of CCA is linked to a wide spectrum of conditions causing biliary inflammation, cholestasis and inflammation of the liver. The geographic diversity of risk factors is reflected in considerable differences in incidence worldwide. Although data are not consistent, incidence seems to be rising in the Western World. Given the limited opportunities of treating advanced CCA, surveillance has been suggested as a strategy for detection of early disease in the high-risk group of patients with primary sclerosing cholangitis (PSC). In this review we present an updated overview of the epidemiology of CCA. We also highlight the risk of CCA in PSC with special focus on surveillance strategies.","Source":"PubMed","category":"HUMAN","training_data":"Epidemiology of cholangiocarcinoma Cholangiocarcinoma (CCA) is a cancer arising from the intra- or extrahepatic bile ducts and mainly characterized by its late diagnosis and fatal outcome. CCA is the second most common primary liver tumour and accounts for approximately 10-15% of all hepatobiliary malignancies. The development of CCA is linked to a wide spectrum of conditions causing biliary inflammation, cholestasis and inflammation of the liver. The geographic diversity of risk factors is reflected in considerable differences in incidence worldwide. Although data are not consistent, incidence seems to be rising in the Western World. Given the limited opportunities of treating advanced CCA, surveillance has been suggested as a strategy for detection of early disease in the high-risk group of patients with primary sclerosing cholangitis (PSC). In this review we present an updated overview of the epidemiology of CCA. We also highlight the risk of CCA in PSC with special focus on surveillance strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"second line therapy advanced biliary tract cancer baseline data retrospective multi centre series background effective first line treatment patients advanced biliary tract cancer btc established median survival approaching 12 months nejm 2010 362 1273 second line regimen established although small retrospective series suggest chemotherapy may active selected patients present results large retrospective series patients undergoing second line chemotherapy institutions across uk use abc 02 standard cisplatin gemcitabine cisgem first line treatment methods patients abc previously treated cisgem went receive second line chemotherapy identified institutional databases demographic data response survival outcome measures collected according agreed proforma results sixty three eligible patients median age 61 6 years range 39 8 78 3 years identified feb 2007 feb 2011 9 centres patients treated mostly platinum based regimen n 42 either re challenge cisgem n 17 oxaliplatin infused 5 fu regimen mfolfox n 17 oxaliplatin capecitabine n 4 patients performance status 0 1 median pfs 4 0 months 95 ci 3 3 5 6 months os 8 1 months 95 ci 5 3 11 4 months following second line therapy demonstrated patients overall os 19 5 months 95 ci 17 0 25 2 months start first line therapy compares median os 11 7 months abc 02 study conclusions use second line chemotherapy advanced btc potential benefit data although retrospective suggests population suitable second line prospective randomised studies chemotherapy targeted agents provide baseline outcome data statistically design studies updated data shown google scholar","probabilities":0.9799733,"Title":"Second-Line Therapy In Advanced Biliary Tract Cancer: Baseline Data From A Retrospective Multi-Centre Series","Abstract":"Background: Effective first-line treatment for patients with advanced biliary tract cancer (BTC) has been established with a median survival of approaching 12 months (NEJM 2010; 362:1273). No second line regimen is established although small retrospective series suggest that chemotherapy may be active in selected patients. We present results of a large retrospective series of patients undergoing second-line chemotherapy at institutions across the UK that use the ABC-02 standard of Cisplatin and Gemcitabine (CisGem) as first-line treatment. Methods: Patients with ABC, previously treated with CisGem and who went on to receive second-line chemotherapy, were identified from institutional databases. Demographic data, response and survival outcome measures were collected according to an agreed proforma. Results: Sixty-three eligible patients (median age: 61.6 years (range: 39.8 – 78.3 years)) were identified between Feb 2007 and Feb 2011, from 9 centres. Patients were treated mostly with a platinum based regimen (n=42), either a re-challenge of CisGem (n=17), an oxaliplatin/ infused 5-FU regimen (mFOLFOX, n=17) or oxaliplatin with capecitabine (n=4). Most patients had a performance status of 0 or 1. A median PFS of 4.0 months (95% CI: 3.3 – 5.6 months) and an OS of 8.1 months (95% CI: 5.3 – 11.4 months) following second line therapy were demonstrated. Patients had an overall OS of 19.5 months (95% CI: 17.0 – 25.2 months) from the start of first-line therapy; this compares with a median OS of 11.7 months from the ABC-02 study. Conclusions: Use of second-line chemotherapy in advanced BTC is of potential benefit. These data, although retrospective, suggests there is a population suitable for second-line, prospective randomised studies with chemotherapy or targeted agents and provide baseline outcome data with which to statistically design such studies. Updated data will be shown.","Source":"Google Scholar","category":"HUMAN","training_data":"Second-Line Therapy In Advanced Biliary Tract Cancer: Baseline Data From A Retrospective Multi-Centre Series Background: Effective first-line treatment for patients with advanced biliary tract cancer (BTC) has been established with a median survival of approaching 12 months (NEJM 2010; 362:1273). No second line regimen is established although small retrospective series suggest that chemotherapy may be active in selected patients. We present results of a large retrospective series of patients undergoing second-line chemotherapy at institutions across the UK that use the ABC-02 standard of Cisplatin and Gemcitabine (CisGem) as first-line treatment. Methods: Patients with ABC, previously treated with CisGem and who went on to receive second-line chemotherapy, were identified from institutional databases. Demographic data, response and survival outcome measures were collected according to an agreed proforma. Results: Sixty-three eligible patients (median age: 61.6 years (range: 39.8 – 78.3 years)) were identified between Feb 2007 and Feb 2011, from 9 centres. Patients were treated mostly with a platinum based regimen (n=42), either a re-challenge of CisGem (n=17), an oxaliplatin/ infused 5-FU regimen (mFOLFOX, n=17) or oxaliplatin with capecitabine (n=4). Most patients had a performance status of 0 or 1. A median PFS of 4.0 months (95% CI: 3.3 – 5.6 months) and an OS of 8.1 months (95% CI: 5.3 – 11.4 months) following second line therapy were demonstrated. Patients had an overall OS of 19.5 months (95% CI: 17.0 – 25.2 months) from the start of first-line therapy; this compares with a median OS of 11.7 months from the ABC-02 study. Conclusions: Use of second-line chemotherapy in advanced BTC is of potential benefit. These data, although retrospective, suggests there is a population suitable for second-line, prospective randomised studies with chemotherapy or targeted agents and provide baseline outcome data with which to statistically design such studies. Updated data will be shown. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"high incidence metastases detected 18f fdg pet ct patients gall bladder cancer incidentally discovered laparoscopic cholecystectomy background gall bladder cancer gbc relatively rare disease clinical imaging features similar benign gall bladder diseases bgbd like gall stone disease cholecystitis bgbd patients undergo laparoscopic cholecystectomy lc later found gbc patients important evaluate extent disease management study conducted evaluate incidence metastases patients referred 18f fluorodeoxyglucose positron emission tomography computed tomography fdg pet ct following incidental discovery gbc lc bgbd methods retrospectively evaluated data patients referred department january 2011 december 2015 fdg pet ct gbc diagnosed histopathology hp lc bgbd abnormal fdg uptake pet images corresponding morphological abnormalities contrast enhanced ct images considered positive disease hp examination clinical imaging follow used reference standard confirmation diagnosis results fdg pet ct imaging performed 1 8 median 3 5 months lc 44 patients 8m 36f aged 30 75 median 50 2 years pet ct positive 32 44 72 7 negative 12 44 patients 27 3 loco regional disease detected 30 44 patients 68 2 involving gall bladder fossa liver regional lymph nodes metastatic seeding omentum mesentery laparoscopic port sites found 15 34 1 distant metastasis 5 patients 11 3 based reference standard 28 patients true positive scans findings 4 scan positive patients confirmed presumed false positive remain follow 12 scan negative patients true negative pet ct showed sensitivity specificity ppv npv accuracy 100 75 0 87 5 100 90 9 respectively detecting residual recurrent disease conclusions high propensity seeding metastasis gbc discovered lc bgbd fdg pet ct high diagnostic performance detecting residual recurrent disease well metastases patients google scholar","probabilities":0.9799733,"Title":"High Incidence Of Metastases Detected On 18F-Fdg Pet-Ct In Patients With Gall Bladder Cancer Incidentally Discovered After Laparoscopic Cholecystectomy","Abstract":"Background\nGall bladder cancer (GBC) is a relatively rare disease with clinical and imaging features similar to benign gall bladder diseases (BGBD) like gall stone disease or cholecystitis. A few of the BGBD patients who undergo laparoscopic cholecystectomy (LC) are later found to have GBC. In these patients, it is important to evaluate the extent of disease for further management. This study was conducted to evaluate the incidence of metastases in patients referred for 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) following incidental discovery of GBC after LC for BGBD.\nMethods\nWe retrospectively evaluated the data of patients referred to our department between January 2011 and December 2015 for FDG PET-CT with GBC diagnosed on histopathology (HP) after LC for BGBD. Abnormal FDG uptake on PET images corresponding to morphological abnormalities on contrast enhanced CT images was considered positive for disease. HP examination and clinical or imaging follow-up were used as the reference standard for confirmation of diagnosis.\nResults\nFDG PET-CT imaging was performed 1-8 (median 3.5) months after LC in 44 patients (8M, 36F) aged 30-75 (median 50.2) years. PET-CT was positive in 32/44 (72.7%) and negative in 12/44 patients (27.3%). Loco-regional disease was detected in 30/44 patients (68.2%) involving the gall bladder fossa, liver or regional lymph nodes. Metastatic seeding to the omentum, mesentery or laparoscopic port sites was found in 15 (34.1%) and distant metastasis in 5 patients (11.3%). Based on the reference standard, 28 patients had true positive scans. Findings in 4 scan-positive patients could not be confirmed; these were presumed false positive and remain on follow-up. All 12 scan-negative patients were true negative. PET-CT showed sensitivity, specificity, PPV, NPV and accuracy of 100%, 75.0%, 87.5%, 100%, and 90.9% respectively in detecting residual / recurrent disease.\nConclusions\nThere is high propensity for seeding metastasis when GBC is discovered after LC for BGBD. FDG PET-CT has high diagnostic performance in detecting residual / recurrent disease as well as metastases in these patients.","Source":"Google Scholar","category":"HUMAN","training_data":"High Incidence Of Metastases Detected On 18F-Fdg Pet-Ct In Patients With Gall Bladder Cancer Incidentally Discovered After Laparoscopic Cholecystectomy Background\nGall bladder cancer (GBC) is a relatively rare disease with clinical and imaging features similar to benign gall bladder diseases (BGBD) like gall stone disease or cholecystitis. A few of the BGBD patients who undergo laparoscopic cholecystectomy (LC) are later found to have GBC. In these patients, it is important to evaluate the extent of disease for further management. This study was conducted to evaluate the incidence of metastases in patients referred for 18F-fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET-CT) following incidental discovery of GBC after LC for BGBD.\nMethods\nWe retrospectively evaluated the data of patients referred to our department between January 2011 and December 2015 for FDG PET-CT with GBC diagnosed on histopathology (HP) after LC for BGBD. Abnormal FDG uptake on PET images corresponding to morphological abnormalities on contrast enhanced CT images was considered positive for disease. HP examination and clinical or imaging follow-up were used as the reference standard for confirmation of diagnosis.\nResults\nFDG PET-CT imaging was performed 1-8 (median 3.5) months after LC in 44 patients (8M, 36F) aged 30-75 (median 50.2) years. PET-CT was positive in 32/44 (72.7%) and negative in 12/44 patients (27.3%). Loco-regional disease was detected in 30/44 patients (68.2%) involving the gall bladder fossa, liver or regional lymph nodes. Metastatic seeding to the omentum, mesentery or laparoscopic port sites was found in 15 (34.1%) and distant metastasis in 5 patients (11.3%). Based on the reference standard, 28 patients had true positive scans. Findings in 4 scan-positive patients could not be confirmed; these were presumed false positive and remain on follow-up. All 12 scan-negative patients were true negative. PET-CT showed sensitivity, specificity, PPV, NPV and accuracy of 100%, 75.0%, 87.5%, 100%, and 90.9% respectively in detecting residual / recurrent disease.\nConclusions\nThere is high propensity for seeding metastasis when GBC is discovered after LC for BGBD. FDG PET-CT has high diagnostic performance in detecting residual / recurrent disease as well as metastases in these patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"fgf19 promotes epithelial mesenchymal transition hepatocellular carcinoma cells modulating gsk3 catenin signaling cascade via fgfr4 activation compelling evidence suggests epithelial mesenchymal transition emt correlates aggressiveness tumors poor survival fgf19 shown involved emt cholangiocarcinoma colorectal cancer however molecular mechanisms underlying fgf19 induced emt process hepatocellular carcinoma hcc remain largely unknown show expression fgf19 significantly elevated negatively associated expression e cadherin hcc tissues cell lines ectopic fgf19 expression promotes emt invasion epithelial like hcc cells repression e cadherin expression whereas fgf19 knockdown enhances e cadherin expression hence diminishes emt traits mesenchymal like hcc cells suggesting fgf19 exerts tumor progressing functions emt inducer interestingly depletion fgf19 abrogate emt traits presence gsk3 inhibitors furthermore fgf19 induced emt markedly attenuated fgfr4 knocked observations clearly indicate fgfr4 gsk3 catenin axis may play pivotal role fgf19 induced emt hcc cells fgf19 specific receptor fgfr4 frequently amplified hcc cells selective targeting signaling node may lend insights potential effective therapeutic approach blocking metastasis hcc pubmed","probabilities":0.875,"Title":"FGF19 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3β/β- catenin signaling cascade via FGFR4 activation","Abstract":"Compelling evidence suggests that the epithelial-mesenchymal transition (EMT) correlates with aggressiveness of tumors and poor survival. FGF19 has been shown to be involved in EMT in cholangiocarcinoma and colorectal cancer, however, molecular mechanisms underlying FGF19-induced EMT process in hepatocellular carcinoma (HCC) remain largely unknown. Here, we show the expression of FGF19 is significantly elevated and negatively associated with the expression of E-cadherin in HCC tissues and cell lines. Ectopic FGF19 expression promotes EMT and invasion in epithelial-like HCC cells through repression of E-cadherin expression, whereas FGF19 knockdown enhances E-cadherin expression and hence diminishes EMT traits in mesenchymal-like HCC cells, suggesting FGF19 exerts its tumor progressing functions as an EMT inducer. Interestingly, depletion of FGF19 cannot abrogate EMT traits in the presence of GSK3β inhibitors. Furthermore, FGF19-induced EMT can be markedly attenuated when FGFR4 is knocked out. These observations clearly indicate that FGFR4/GSK3β/β-catenin axis may play a pivotal role in FGF19-induced EMT in HCC cells. As FGF19 and its specific receptor FGFR4 are frequently amplified in HCC cells, selective targeting this signaling node may lend insights into a potential effective therapeutic approach for blocking metastasis of HCC.","Source":"PubMed","category":"ANIMAL","training_data":"FGF19 promotes epithelial-mesenchymal transition in hepatocellular carcinoma cells by modulating the GSK3β/β- catenin signaling cascade via FGFR4 activation Compelling evidence suggests that the epithelial-mesenchymal transition (EMT) correlates with aggressiveness of tumors and poor survival. FGF19 has been shown to be involved in EMT in cholangiocarcinoma and colorectal cancer, however, molecular mechanisms underlying FGF19-induced EMT process in hepatocellular carcinoma (HCC) remain largely unknown. Here, we show the expression of FGF19 is significantly elevated and negatively associated with the expression of E-cadherin in HCC tissues and cell lines. Ectopic FGF19 expression promotes EMT and invasion in epithelial-like HCC cells through repression of E-cadherin expression, whereas FGF19 knockdown enhances E-cadherin expression and hence diminishes EMT traits in mesenchymal-like HCC cells, suggesting FGF19 exerts its tumor progressing functions as an EMT inducer. Interestingly, depletion of FGF19 cannot abrogate EMT traits in the presence of GSK3β inhibitors. Furthermore, FGF19-induced EMT can be markedly attenuated when FGFR4 is knocked out. These observations clearly indicate that FGFR4/GSK3β/β-catenin axis may play a pivotal role in FGF19-induced EMT in HCC cells. As FGF19 and its specific receptor FGFR4 are frequently amplified in HCC cells, selective targeting this signaling node may lend insights into a potential effective therapeutic approach for blocking metastasis of HCC. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"metastasectomy recurrent metastatic biliary tract cancers single center experience purpose assess efficacy long term result metastasectomy recurrent metastatic biliary tract carcinoma btc conducted retrospective review outcomes metastasectomy recurrent metastatic btcs comprising intrahepatic cholangiocellular carcinoma ihccc proximal distal common bile duct cancer pcbdc dcbdc gallbladder cancer gbc ampulla vater cancer aovc patients methods clinicopathological features outcomes btc patients underwent surgical resection primary metastatic disease gachon university gil medical centre 2003 2013 reviewed retrospectively results found 19 eligible patients primary sites gbc seven patients 37 ihccc five patients 26 dcbdc three patients 16 pcbdc two patients 11 aovc two patients 11 eight patients 42 synchronous metastasis whereas 11 58 metachronous metastasis common metastatic site liver nine patients 47 lymph node nine patients 47 peritoneum three patients 16 nine patients 47 achieved r0 resection whereas four 21 six 32 patients r1 r2 resection respectively median follow period 26 7 months estimated median overall survival os 18 2 months 95 confidence interval 13 6 22 9 months lower eastern cooperative oncology group performance status p 0 023 metachronous metastasis p 0 04 absence lymph node metastasis p 0 009 lower numbers metastatic organs p 0 001 normal postoperative ca19 9 level p 0 034 time diagnosis metastasectomy 1 year p 0 019 identified prognostic factors longer os metastasectomy conclusions recurrent metastatic btcs metastasectomy viable option selected patients pubmed","probabilities":0.9799733,"Title":"Metastasectomy for recurrent or metastatic biliary tract cancers: A single center experience","Abstract":"PURPOSE: To assess efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC), we conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs, comprising intrahepatic cholangiocellular carcinoma (IHCCC), proximal and distal common bile duct cancer (pCBDC and dCBDC), gallbladder cancer (GBC), and ampulla of Vater cancer (AoVC). PATIENTS AND METHODS: The clinicopathological features and outcomes of BTC patients who underwent surgical resection for the primary and metastatic disease at the Gachon University Gil Medical Centre from 2003 to 2013 were reviewed retrospectively. RESULTS: We found 19 eligible patients. Primary sites were GBC (seven patients, 37%), IHCCC (five patients, 26%), dCBDC (three patients, 16%), pCBDC (two patients, 11%), and AoVC (two patients, 11%). Eight patients (42%) had synchronous metastasis whereas 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, whereas four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval, 13.6-22.9 months). Lower Eastern Cooperative Oncology Group performance status (P = 0.023), metachronous metastasis (P = 0.04), absence of lymph node metastasis (P = 0.009), lower numbers of metastatic organs (P < 0.001), normal postoperative CA19-9 level (P = 0.034), and time from diagnosis to metastasectomy more than 1 year (P = 0.019) were identified as prognostic factors for a longer OS after metastasectomy. CONCLUSIONS: For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients.","Source":"PubMed","category":"HUMAN","training_data":"Metastasectomy for recurrent or metastatic biliary tract cancers: A single center experience PURPOSE: To assess efficacy or long-term result of metastasectomy for recurrent or metastatic biliary tract carcinoma (BTC), we conducted a retrospective review of the outcomes of metastasectomy for recurrent or metastatic BTCs, comprising intrahepatic cholangiocellular carcinoma (IHCCC), proximal and distal common bile duct cancer (pCBDC and dCBDC), gallbladder cancer (GBC), and ampulla of Vater cancer (AoVC). PATIENTS AND METHODS: The clinicopathological features and outcomes of BTC patients who underwent surgical resection for the primary and metastatic disease at the Gachon University Gil Medical Centre from 2003 to 2013 were reviewed retrospectively. RESULTS: We found 19 eligible patients. Primary sites were GBC (seven patients, 37%), IHCCC (five patients, 26%), dCBDC (three patients, 16%), pCBDC (two patients, 11%), and AoVC (two patients, 11%). Eight patients (42%) had synchronous metastasis whereas 11 (58%) had metachronous metastasis. The most common metastatic site was liver (nine patients, 47%), lymph node (nine patients, 47%), and peritoneum (three patients, 16%). Nine patients (47%) achieved R0 resection, whereas four (21%) and six (32%) patients had R1 and R2 resection, respectively. With a median follow-up period of 26.7 months, the estimated median overall survival (OS) was 18.2 months (95% confidence interval, 13.6-22.9 months). Lower Eastern Cooperative Oncology Group performance status (P = 0.023), metachronous metastasis (P = 0.04), absence of lymph node metastasis (P = 0.009), lower numbers of metastatic organs (P < 0.001), normal postoperative CA19-9 level (P = 0.034), and time from diagnosis to metastasectomy more than 1 year (P = 0.019) were identified as prognostic factors for a longer OS after metastasectomy. CONCLUSIONS: For recurrent or metastatic BTCs, metastasectomy can be a viable option for selected patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic heterogeneity seventh edition uicc stage iii gallbladder carcinoma patients benefit surgical resection background study sought evaluate prognostic heterogeneity stage iii union international cancer control seventh edition gallbladder carcinoma methods 175 patients enrolled gallbladder carcinoma underwent radical resection 22 classified stage iiia disease t3n0m0 46 stage iiib disease t2n1m0 n 23 t3n1m0 n 23 median number retrieved lymph nodes per patient 18 results staging system failed stratify outcomes stages iiia iiib survival resection better patients stage iiib disease patients stage iiia disease 5 year survival 54 9 41 0 respectively p 0 366 multivariate analysis patients stage iii disease revealed independently better survival patients t2n1m0 patients t3n0m0 p 0 016 t3n1m0 p 0 001 5 year survival 77 0 41 0 31 0 respectively n1 status subdivided according number positive nodes 5 year survival patients t2m0 1 2 positive nodes t2m0 3 positive nodes t3m0 1 2 positive nodes t3m0 3 positive nodes 83 3 50 0 45 8 0 respectively p 0 001 conclusions prognosis t2n1m0 disease better t3n0 1m0 disease suggesting node positive patients uniformly poor outcomes resection gallbladder carcinoma t2m0 1 2 positive nodes leads favorable outcome resection whereas t3m0 3 positive nodes indicates dismal prognosis pubmed","probabilities":0.9799733,"Title":"Prognostic heterogeneity of the seventh edition of UICC Stage III gallbladder carcinoma: Which patients benefit from surgical resection?","Abstract":"BACKGROUND: This study sought to evaluate the prognostic heterogeneity of Stage III (Union for International Cancer Control, seventh edition) gallbladder carcinoma. METHODS: Of 175 patients enrolled with gallbladder carcinoma who underwent radical resection, 22 were classified with Stage IIIA disease (T3N0M0) and 46 with Stage IIIB disease (T2N1M0 [n = 23] and T3N1M0 [n = 23]). The median number of retrieved lymph nodes per patient was 18. RESULTS: This staging system failed to stratify outcomes between Stages IIIA and IIIB; survival after resection was better for patients with Stage IIIB disease than for patients with Stage IIIA disease, with 5-year survival of 54.9% and 41.0%, respectively (p = 0.366). Multivariate analysis for patients with Stage III disease revealed independently better survival for patients with T2N1M0 than for patients with T3N0M0 (p = 0.016) or T3N1M0 (p = 0.001), with 5-year survival of 77.0%, 41.0%, and 31.0%, respectively. When N1 status was subdivided according to the number of positive nodes, 5-year survival in patients with T2M0 with 1-2 positive nodes, T2M0 with ≥3 positive nodes, T3M0 with 1-2 positive nodes, and T3M0 with ≥3 positive nodes was 83.3%, 50.0%, 45.8%, and 0%, respectively (p < 0.001). CONCLUSIONS: The prognosis of T2N1M0 disease was better than that of T3N0/1M0 disease, suggesting that not all node-positive patients will have uniformly poor outcomes after resection of gallbladder carcinoma. T2M0 with 1-2 positive nodes leads to a favorable outcome after resection, whereas T3M0 with ≥3 positive nodes indicates a dismal prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic heterogeneity of the seventh edition of UICC Stage III gallbladder carcinoma: Which patients benefit from surgical resection? BACKGROUND: This study sought to evaluate the prognostic heterogeneity of Stage III (Union for International Cancer Control, seventh edition) gallbladder carcinoma. METHODS: Of 175 patients enrolled with gallbladder carcinoma who underwent radical resection, 22 were classified with Stage IIIA disease (T3N0M0) and 46 with Stage IIIB disease (T2N1M0 [n = 23] and T3N1M0 [n = 23]). The median number of retrieved lymph nodes per patient was 18. RESULTS: This staging system failed to stratify outcomes between Stages IIIA and IIIB; survival after resection was better for patients with Stage IIIB disease than for patients with Stage IIIA disease, with 5-year survival of 54.9% and 41.0%, respectively (p = 0.366). Multivariate analysis for patients with Stage III disease revealed independently better survival for patients with T2N1M0 than for patients with T3N0M0 (p = 0.016) or T3N1M0 (p = 0.001), with 5-year survival of 77.0%, 41.0%, and 31.0%, respectively. When N1 status was subdivided according to the number of positive nodes, 5-year survival in patients with T2M0 with 1-2 positive nodes, T2M0 with ≥3 positive nodes, T3M0 with 1-2 positive nodes, and T3M0 with ≥3 positive nodes was 83.3%, 50.0%, 45.8%, and 0%, respectively (p < 0.001). CONCLUSIONS: The prognosis of T2N1M0 disease was better than that of T3N0/1M0 disease, suggesting that not all node-positive patients will have uniformly poor outcomes after resection of gallbladder carcinoma. T2M0 with 1-2 positive nodes leads to a favorable outcome after resection, whereas T3M0 with ≥3 positive nodes indicates a dismal prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"liver transplantation appropriate patients potentially resectable de novo hilar cholangiocarcinoma background liver transplantation ltx curative selected patients hilar cholangiocarcinoma hc setting sclerosing cholangitis however outcome ltx vs liver resection rtx patients de novo hc remains unclear study design patients de novo hc treated protocol ltx n 90 rtx n 124 1993 2013 reviewed based preoperative imaging rtx pursued bismuth type iii hc ltx unresectable bismuth type iv results unadjusted analysis showed overall survival operation greater ltx rtx p 0 003 one 3 5 year overall survival rates respectively 90 71 59 ltx 81 53 36 rtx survival different ltx rtx adjusting patient age lymph node metastases tumor size postoperative pathologic review hc rtx reclassified bismuth corlette b c iv based necessity multiple biliary anastomoses 40 patients accurately compare treatment outcomes overall survival greater ltx rtx p 0 039 patients bismuth corlette iv hc conclusions patients clearly resectable de novo hc treated resection evidence fare better ltx patients locally unresectable de novo hc meeting criteria protocol treated ltx decision proceed rtx ltx patients borderline resectable de novo hc remains difficult results suggest patients b c type iv hc might best treated transplantation excellent transplant candidates pubmed","probabilities":0.9799733,"Title":"Is Liver Transplantation Appropriate for Patients with Potentially Resectable De Novo Hilar Cholangiocarcinoma?","Abstract":"BACKGROUND: Liver transplantation (LTX) is curative for selected patients with hilar cholangiocarcinoma (HC) in the setting of sclerosing cholangitis. However, the outcome of LTX vs liver resection (RTX) for patients with de novo HC remains unclear. STUDY DESIGN: Patients with de novo HC treated by protocol LTX (n = 90) or RTX (n = 124) between 1993 and 2013 were reviewed. Based on preoperative imaging, RTX was pursued for Bismuth type III HC and LTX for unresectable Bismuth type IV. RESULTS: Unadjusted analysis showed that overall survival after operation was greater for LTX than RTX (p = 0.003). One-, 3-, and 5-year overall survival rates, respectively, were 90%, 71%, and 59% for LTX and 81%, 53%, and 36% for RTX. Survival was not different between LTX and RTX after adjusting for patient age, lymph node metastases, and tumor size. After postoperative pathologic review, HC after RTX was reclassified as Bismuth-Corlette (B-C) IV, based on the necessity of multiple biliary anastomoses in 40 patients to more accurately compare treatment outcomes. Overall survival was greater after LTX than RTX (p = 0.039) for patients with Bismuth-Corlette IV HC. CONCLUSIONS: Patients with clearly resectable de novo HC should be treated with resection because there is no evidence that they would fare better with LTX. Patients with locally unresectable de novo HC, meeting criteria for our protocol, should be treated with LTX. The decision to proceed with RTX or LTX for patients with borderline resectable de novo HC remains difficult, but our results suggest that patients with B-C type IV HC might be best treated with transplantation, if they are excellent transplant candidates.","Source":"PubMed","category":"HUMAN","training_data":"Is Liver Transplantation Appropriate for Patients with Potentially Resectable De Novo Hilar Cholangiocarcinoma? BACKGROUND: Liver transplantation (LTX) is curative for selected patients with hilar cholangiocarcinoma (HC) in the setting of sclerosing cholangitis. However, the outcome of LTX vs liver resection (RTX) for patients with de novo HC remains unclear. STUDY DESIGN: Patients with de novo HC treated by protocol LTX (n = 90) or RTX (n = 124) between 1993 and 2013 were reviewed. Based on preoperative imaging, RTX was pursued for Bismuth type III HC and LTX for unresectable Bismuth type IV. RESULTS: Unadjusted analysis showed that overall survival after operation was greater for LTX than RTX (p = 0.003). One-, 3-, and 5-year overall survival rates, respectively, were 90%, 71%, and 59% for LTX and 81%, 53%, and 36% for RTX. Survival was not different between LTX and RTX after adjusting for patient age, lymph node metastases, and tumor size. After postoperative pathologic review, HC after RTX was reclassified as Bismuth-Corlette (B-C) IV, based on the necessity of multiple biliary anastomoses in 40 patients to more accurately compare treatment outcomes. Overall survival was greater after LTX than RTX (p = 0.039) for patients with Bismuth-Corlette IV HC. CONCLUSIONS: Patients with clearly resectable de novo HC should be treated with resection because there is no evidence that they would fare better with LTX. Patients with locally unresectable de novo HC, meeting criteria for our protocol, should be treated with LTX. The decision to proceed with RTX or LTX for patients with borderline resectable de novo HC remains difficult, but our results suggest that patients with B-C type IV HC might be best treated with transplantation, if they are excellent transplant candidates. PubMed","prediction_labels":"HUMAN"},{"cleaned":"risk factors cholangiocarcinoma cholangiocarcinoma cc second common primary hepatic malignancy hepatocellular cancer cc accounts approximately 10 25 hepatobiliary malignancies considerable geographic demographic variations incidence cc several established risk factors cc including parasitic infections primary sclerosing cholangitis biliary duct cysts hepatolithiasis toxins less established potential risk factors include inflammatory bowel disease hepatitis c virus hepatitis b virus cirrhosis diabetes obesity alcohol drinking tobacco smoking host genetic polymorphisms studies distinction intra extrahepatic cc used potential risk factors seem differential effect cc depending site therefore consistent use refined classification allow better understanding risk factors cc pubmed","probabilities":0.9799733,"Title":"Risk factors for cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy after hepatocellular cancer. CC accounts for approximately 10%-25% of all hepatobiliary malignancies. There are considerable geographic and demographic variations in the incidence of CC. There are several established risk factors for CC, including parasitic infections, primary sclerosing cholangitis, biliary-duct cysts, hepatolithiasis, and toxins. Other less-established potential risk factors include inflammatory bowel disease, hepatitis C virus, hepatitis B virus, cirrhosis, diabetes, obesity, alcohol drinking, tobacco smoking, and host genetic polymorphisms. In studies where the distinction between intra- and extrahepatic CC was used, some potential risk factors seem to have a differential effect on CC, depending on the site. Therefore, the consistent use of a more refined classification would allow a better understanding of risk factors for CC.","Source":"PubMed","category":"HUMAN","training_data":"Risk factors for cholangiocarcinoma Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy after hepatocellular cancer. CC accounts for approximately 10%-25% of all hepatobiliary malignancies. There are considerable geographic and demographic variations in the incidence of CC. There are several established risk factors for CC, including parasitic infections, primary sclerosing cholangitis, biliary-duct cysts, hepatolithiasis, and toxins. Other less-established potential risk factors include inflammatory bowel disease, hepatitis C virus, hepatitis B virus, cirrhosis, diabetes, obesity, alcohol drinking, tobacco smoking, and host genetic polymorphisms. In studies where the distinction between intra- and extrahepatic CC was used, some potential risk factors seem to have a differential effect on CC, depending on the site. Therefore, the consistent use of a more refined classification would allow a better understanding of risk factors for CC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"enhanced cytotoxic activity effector cells cholangiocarcinoma dendritic cells pulsed pooled mrna cholangiocarcinoma malignancy bile duct epithelia increasing incidence rate worldwide surgery curative treatment adjuvant chemotherapy radiotherapy render poor responses cell based immunotherapy potential strategy cholangiocarcinoma treatment however variation tumor antigens cholangiocarcinoma leads ineffectiveness cell based immunotherapy study examined activation effector cells dendritic cells pulsed protein lysate total rna cholangiocarcinoma cell lines cytolytic activity cholangiocarcinoma broad spectrum antigen types respect rna antigen sources obtained combination three cholangiocarcinoma cell lines kku 213 kku 100 kku 055 compared protein lysate pulsed dendritic cells total rna pulsed dendritic cells induced anti tumor effector cell response higher killing ability kku 100 kku 213 cells compared protein lysate pulsed dendritic cells moreover pooled messenger rna three cholangiocarcinoma cell lines significantly increased specific killing capacity activated lymphocytes kku 213 cells results suggest activation anti tumor effector cells cholangiocarcinoma rna pulsed dendritic cells effective protein lysate pulsed dendritic cells addition pulsing dendritic cells pooled messenger rna multiple cell lines enhanced efficacy cellular immune response cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Enhanced Cytotoxic Activity Of Effector T-Cells Against Cholangiocarcinoma By Dendritic Cells Pulsed With Pooled Mrna","Abstract":"Cholangiocarcinoma is a malignancy of bile duct epithelia with an increasing in incidence rate worldwide. Surgery is the only curative treatment, while adjuvant chemotherapy and radiotherapy render poor responses. Cell-based immunotherapy is a potential strategy for cholangiocarcinoma treatment. However, variation of tumor antigens in cholangiocarcinoma leads to the ineffectiveness of cell-based immunotherapy. In this study, we examined the activation of effector T-cells by dendritic cells pulsed with protein lysate or total RNA from cholangiocarcinoma cell lines for their cytolytic activity against cholangiocarcinoma. Broad-spectrum antigen types with respect to RNA antigen sources were obtained from combination of three cholangiocarcinoma cell lines (KKU-213, KKU-100, and KKU-055). Compared with protein lysate-pulsed dendritic cells, total RNA-pulsed dendritic cells induced anti-tumor effector T-cell response with higher killing ability to KKU-100 and KKU-213 cells compared with protein lysate-pulsed dendritic cells. Moreover, pooled messenger RNA from three cholangiocarcinoma cell lines significantly increased the specific killing capacity of activated lymphocytes against KKU-213 cells. These results suggest that activation of anti-tumor effector T-cells against cholangiocarcinoma by RNA-pulsed dendritic cells is more effective than that by protein lysate-pulsed dendritic cells. In addition, pulsing dendritic cells with pooled messenger RNA from multiple cell lines enhanced the efficacy of a cellular immune response against cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Enhanced Cytotoxic Activity Of Effector T-Cells Against Cholangiocarcinoma By Dendritic Cells Pulsed With Pooled Mrna Cholangiocarcinoma is a malignancy of bile duct epithelia with an increasing in incidence rate worldwide. Surgery is the only curative treatment, while adjuvant chemotherapy and radiotherapy render poor responses. Cell-based immunotherapy is a potential strategy for cholangiocarcinoma treatment. However, variation of tumor antigens in cholangiocarcinoma leads to the ineffectiveness of cell-based immunotherapy. In this study, we examined the activation of effector T-cells by dendritic cells pulsed with protein lysate or total RNA from cholangiocarcinoma cell lines for their cytolytic activity against cholangiocarcinoma. Broad-spectrum antigen types with respect to RNA antigen sources were obtained from combination of three cholangiocarcinoma cell lines (KKU-213, KKU-100, and KKU-055). Compared with protein lysate-pulsed dendritic cells, total RNA-pulsed dendritic cells induced anti-tumor effector T-cell response with higher killing ability to KKU-100 and KKU-213 cells compared with protein lysate-pulsed dendritic cells. Moreover, pooled messenger RNA from three cholangiocarcinoma cell lines significantly increased the specific killing capacity of activated lymphocytes against KKU-213 cells. These results suggest that activation of anti-tumor effector T-cells against cholangiocarcinoma by RNA-pulsed dendritic cells is more effective than that by protein lysate-pulsed dendritic cells. In addition, pulsing dendritic cells with pooled messenger RNA from multiple cell lines enhanced the efficacy of a cellular immune response against cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"body mass index risk cancer women compared men meta analysis prospective cohort studies studies investigating association bmi risk common cancers men women reported inconsistent results searched pubmed embase cochrane library electronic databases relevant articles published april 2015 overall analyzed 128 datasets 51 articles including 154 939 incident cancer cases pooled relative risk ratio rrr female male showed relative risk overweight associated colorectal rrr 0 91 95 confidence interval ci 0 85 0 97 rectal cancer rrr 0 94 95 ci 0 88 0 99 significantly lower women men however relative risk overweight associated lung rrr 1 14 95 ci 1 06 1 22 kidney cancer rrr 1 15 95 ci 1 05 1 26 significantly higher women men furthermore relative risk obesity associated liver rrr 0 71 95 ci 0 51 0 99 colorectal rrr 0 83 95 ci 0 75 0 93 colon rrr 0 73 95 ci 0 68 0 0 78 rectal rrr 0 84 95 ci 0 76 0 92 kidney cancer rrr 1 20 95 ci 1 06 1 37 differed significantly women men finally relative risk underweight associated gastric rrr 0 83 95 ci 0 70 0 97 liver rrr 0 83 95 ci 0 71 0 97 gallbladder cancer rrr 1 25 95 ci 1 04 1 49 differed significantly according sex conclusion study showed association bmi risk several cancers significantly different sexes cancer types sex difference affected country sample size follow duration study quality pubmed","probabilities":0.9799733,"Title":"Body mass index and the risk of cancer in women compared with men: a meta-analysis of prospective cohort studies","Abstract":"Studies investigating the association between BMI and the risk of the common cancers in men or women have reported inconsistent results. We searched the PubMed, Embase, and Cochrane Library electronic databases for relevant articles published until April 2015. Overall, we analyzed 128 datasets (51 articles), including 154 939 incident cancer cases. The pooled relative risk ratio (RRR) (female to male) showed that the relative risk of overweight associated with colorectal [RRR: 0.91; 95% confidence interval (CI): 0.85-0.97] or rectal cancer (RRR: 0.94; 95% CI: 0.88-0.99) was significantly lower in women than in men. However, the relative risk of overweight associated with lung (RRR: 1.14; 95% CI: 1.06-1.22) or kidney cancer (RRR: 1.15; 95% CI: 1.05-1.26) was significantly higher in women than in men. Furthermore, the relative risk of obesity associated with liver (RRR: 0.71; 95% CI: 0.51-0.99), colorectal (RRR: 0.83; 95% CI: 0.75-0.93), colon (RRR: 0.73; 95% CI: 0.68-0.0.78), rectal (RRR: 0.84; 95% CI: 0.76-0.92), and kidney cancer (RRR: 1.20; 95% CI: 1.06-1.37) differed significantly between women and men. Finally, the relative risk of underweight associated with gastric (RRR: 0.83; 95% CI: 0.70-0.97), liver (RRR: 0.83; 95% CI: 0.71-0.97), and gallbladder cancer (RRR: 1.25; 95% CI: 1.04-1.49) differed significantly according to sex. In conclusion, our study showed that the association between BMI and the risk of several cancers was significantly different between the sexes. For some cancer types, the sex difference was affected by country, sample size, follow-up duration, and study quality.","Source":"PubMed","category":"HUMAN","training_data":"Body mass index and the risk of cancer in women compared with men: a meta-analysis of prospective cohort studies Studies investigating the association between BMI and the risk of the common cancers in men or women have reported inconsistent results. We searched the PubMed, Embase, and Cochrane Library electronic databases for relevant articles published until April 2015. Overall, we analyzed 128 datasets (51 articles), including 154 939 incident cancer cases. The pooled relative risk ratio (RRR) (female to male) showed that the relative risk of overweight associated with colorectal [RRR: 0.91; 95% confidence interval (CI): 0.85-0.97] or rectal cancer (RRR: 0.94; 95% CI: 0.88-0.99) was significantly lower in women than in men. However, the relative risk of overweight associated with lung (RRR: 1.14; 95% CI: 1.06-1.22) or kidney cancer (RRR: 1.15; 95% CI: 1.05-1.26) was significantly higher in women than in men. Furthermore, the relative risk of obesity associated with liver (RRR: 0.71; 95% CI: 0.51-0.99), colorectal (RRR: 0.83; 95% CI: 0.75-0.93), colon (RRR: 0.73; 95% CI: 0.68-0.0.78), rectal (RRR: 0.84; 95% CI: 0.76-0.92), and kidney cancer (RRR: 1.20; 95% CI: 1.06-1.37) differed significantly between women and men. Finally, the relative risk of underweight associated with gastric (RRR: 0.83; 95% CI: 0.70-0.97), liver (RRR: 0.83; 95% CI: 0.71-0.97), and gallbladder cancer (RRR: 1.25; 95% CI: 1.04-1.49) differed significantly according to sex. In conclusion, our study showed that the association between BMI and the risk of several cancers was significantly different between the sexes. For some cancer types, the sex difference was affected by country, sample size, follow-up duration, and study quality. PubMed","prediction_labels":"HUMAN"},{"cleaned":"immunohistochemical expression phospho mtor associated poor prognosis patients gallbladder adenocarcinoma context advanced gallbladder carcinoma gbc highly fatal disease poor prognosis therapeutic alternatives mammalian target rapamycin mtor serine threonine kinase plays central role cell growth homeostasis regulation frequently altered various tumors attractive target cancer therapy however status gbc remains unclear objective characterize immunohistochemical expression prognostic significance phospho mtor advanced gallbladder carcinoma design phospho mtor expression examined immunohistochemistry tissue microarrays containing 128 advanced gbcs 99 cases chronic cholecystitis divided 2 groups according presence absence metaplasia evaluate association level phospho mtor expression clinical variables patient survival advanced gbcs classified low high expression statistical analysis performed using significance level p 05 kaplan meier curves constructed survival analysis results immunostaining phospho mtor positive 82 128 tumors 64 1 24 chronic cholecystitis cases 16 nonmetaplasia 32 metaplasia p 001 survival analysis indicated high phospho mtor immunohistochemical expression associated poorer prognosis patients advanced gbc p 02 conclusions metaplasia common finding chronic cholecystitis considered precursor lesion dysplasia results suggest activation mtor occurs early development gbc contributing carcinogenesis process phospho mtor expression correlated poor survival supporting potential mtor targeted therapy pubmed","probabilities":0.962963,"Title":"Immunohistochemical expression of phospho-mTOR is associated with poor prognosis in patients with gallbladder adenocarcinoma","Abstract":"CONTEXT: Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear. OBJECTIVE: To characterize immunohistochemical expression and prognostic significance of phospho-mTOR in advanced gallbladder carcinoma. DESIGN: Phospho-mTOR expression was examined by immunohistochemistry in tissue microarrays containing 128 advanced GBCs and 99 cases of chronic cholecystitis, which were divided into 2 groups according to the presence or absence of metaplasia. To evaluate the association of the level of phospho-mTOR expression with clinical variables and patient survival, the advanced GBCs were classified as having low or high expression. Statistical analysis was performed by using a significance level of P < .05, and Kaplan-Meier curves were constructed for survival analysis. RESULTS: Immunostaining for phospho-mTOR was positive in 82 of 128 tumors (64.1%) and in 24% of chronic cholecystitis cases (16% nonmetaplasia and 32% with metaplasia) (P < .001). Survival analysis indicated that a high phospho-mTOR immunohistochemical expression was associated with poorer prognosis in patients with advanced GBC (P = .02). CONCLUSIONS: Metaplasia is a common finding in chronic cholecystitis and is considered a precursor lesion of dysplasia. Our results suggest that the activation of mTOR occurs very early during the development of GBC, contributing to the carcinogenesis process. Phospho-mTOR expression is correlated with poor survival, supporting the potential of mTOR for targeted therapy.","Source":"PubMed","category":"HUMAN","training_data":"Immunohistochemical expression of phospho-mTOR is associated with poor prognosis in patients with gallbladder adenocarcinoma CONTEXT: Advanced gallbladder carcinoma (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that plays a central role in cell growth and homeostasis. Its regulation is frequently altered in various tumors and is an attractive target for cancer therapy; however, its status in GBC remains unclear. OBJECTIVE: To characterize immunohistochemical expression and prognostic significance of phospho-mTOR in advanced gallbladder carcinoma. DESIGN: Phospho-mTOR expression was examined by immunohistochemistry in tissue microarrays containing 128 advanced GBCs and 99 cases of chronic cholecystitis, which were divided into 2 groups according to the presence or absence of metaplasia. To evaluate the association of the level of phospho-mTOR expression with clinical variables and patient survival, the advanced GBCs were classified as having low or high expression. Statistical analysis was performed by using a significance level of P < .05, and Kaplan-Meier curves were constructed for survival analysis. RESULTS: Immunostaining for phospho-mTOR was positive in 82 of 128 tumors (64.1%) and in 24% of chronic cholecystitis cases (16% nonmetaplasia and 32% with metaplasia) (P < .001). Survival analysis indicated that a high phospho-mTOR immunohistochemical expression was associated with poorer prognosis in patients with advanced GBC (P = .02). CONCLUSIONS: Metaplasia is a common finding in chronic cholecystitis and is considered a precursor lesion of dysplasia. Our results suggest that the activation of mTOR occurs very early during the development of GBC, contributing to the carcinogenesis process. Phospho-mTOR expression is correlated with poor survival, supporting the potential of mTOR for targeted therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic relevance lymph node ratio surgical patients extrahepatic cholangiocarcinoma aim studies investigated influence lymph node ratio lnr ratio number lymph nodes harboring metastatic cancer total number lymph nodes removed outcome surgery extrahepatic cholangiocarcinoma study conducted examine prognostic impact lnr patients undergoing resection extrahepatic cholangiocarcinoma patients methods retrospectively analyzed total 60 consecutive patients underwent resection extrahepatic cholangiocarcinoma focused lnr classified 0 34 patients 0 0 2 13 patients greater 0 2 13 patients results overall five year survival rates patients lnrs 0 0 0 2 0 2 44 10 0 respectively p 0 023 lnr independent predictive factor estimated survival univariate p 0 016 multivariate p 0 022 analyses including lnr sites primary tumors surgical margin variables statistically significant differences patients less 12 lymph nodes removed 12 lymph nodes removed p 0 484 conclusion lnr powerful independent predictor estimated survival patients undergoing surgical resection extrahepatic cholangiocarcinoma lnr considered stratifying patients future clinical trials pubmed","probabilities":0.9799733,"Title":"Prognostic relevance of the lymph node ratio in surgical patients with extrahepatic cholangiocarcinoma","Abstract":"AIM: Few studies have investigated the influence of the lymph node ratio (LNR), the ratio of the number of lymph nodes harboring metastatic cancer to the total number of lymph nodes removed, on the outcome after surgery for extrahepatic cholangiocarcinoma. This study was conducted to examine the prognostic impact of LNR in patients undergoing resection for extrahepatic cholangiocarcinoma. PATIENTS AND METHODS: We retrospectively analyzed a total of 60 consecutive patients who underwent resection for extrahepatic cholangiocarcinoma. We focused on the LNR, which was classified as 0 in 34 patients, between 0 and 0.2 in 13 patients, and greater than 0.2 in 13 patients. RESULTS: The overall five-year survival rates for patients with LNRs of 0, 0 to 0.2, and ≥0.2 were 44%, 10%, and 0%, respectively (p = 0.023). LNR was an independent predictive factor for estimated survival by both univariate (p = 0.016) and multivariate (p = 0.022) analyses including LNR, the sites of the primary tumors, and surgical margin as the variables. There were no statistically significant differences between patients who had less than 12 lymph nodes removed and those who had 12 or more lymph nodes removed (p = 0.484). CONCLUSION: LNR was a powerful, independent predictor of estimated survival in patients undergoing surgical resection for extrahepatic cholangiocarcinoma. LNR should be considered when stratifying patients for future clinical trials.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic relevance of the lymph node ratio in surgical patients with extrahepatic cholangiocarcinoma AIM: Few studies have investigated the influence of the lymph node ratio (LNR), the ratio of the number of lymph nodes harboring metastatic cancer to the total number of lymph nodes removed, on the outcome after surgery for extrahepatic cholangiocarcinoma. This study was conducted to examine the prognostic impact of LNR in patients undergoing resection for extrahepatic cholangiocarcinoma. PATIENTS AND METHODS: We retrospectively analyzed a total of 60 consecutive patients who underwent resection for extrahepatic cholangiocarcinoma. We focused on the LNR, which was classified as 0 in 34 patients, between 0 and 0.2 in 13 patients, and greater than 0.2 in 13 patients. RESULTS: The overall five-year survival rates for patients with LNRs of 0, 0 to 0.2, and ≥0.2 were 44%, 10%, and 0%, respectively (p = 0.023). LNR was an independent predictive factor for estimated survival by both univariate (p = 0.016) and multivariate (p = 0.022) analyses including LNR, the sites of the primary tumors, and surgical margin as the variables. There were no statistically significant differences between patients who had less than 12 lymph nodes removed and those who had 12 or more lymph nodes removed (p = 0.484). CONCLUSION: LNR was a powerful, independent predictor of estimated survival in patients undergoing surgical resection for extrahepatic cholangiocarcinoma. LNR should be considered when stratifying patients for future clinical trials. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance circulating intact cleaved forms urokinase plasminogen activator receptor inoperable chemotherapy treated cholangiocarcinoma patients background high levels intact cleaved forms urokinase type plasminogen activator receptor upar tissue blood associated poor survival several cancer diseases prognostic significance upar cholangiocarcinoma unknown aims study determine pre treatment serum levels upar forms decrease levels chemotherapy predictive survival patients inoperable cholangiocarcinoma design methods patients inoperable cholangiocarcinoma consecutively included training set n 108 test set included patients different hospital using similar treatment guidelines n 60 serum levels different upar forms determined using time resolved fluorescence immunoassays tr fia cox proportional hazards model used uni multivariate survival analyses results baseline level upar iii upar ii iii independent predictor survival hr 2 08 95 ci 1 46 2 97 p 0 0001 applying linear predictor training set test set validated upar iii upar ii iii predicted overall survival p 0 049 high level upar iii upar ii iii 2cycles chemotherapy associated poor survival hr 1 79 95 ci 1 08 2 97 p 0 023 n 57 predictor however significant test set p 0 21 26 events 27 patients conclusion baseline level upar iii upar ii iii predictor survival inoperable cholangiocarcinoma patients pubmed","probabilities":0.7966102,"Title":"Prognostic significance of circulating intact and cleaved forms of urokinase plasminogen activator receptor in inoperable chemotherapy treated cholangiocarcinoma patients","Abstract":"BACKGROUND: High levels of intact and cleaved forms of the urokinase-type plasminogen activator receptor (uPAR) in both tissue and blood are associated with poor survival in several cancer diseases. The prognostic significance of uPAR in cholangiocarcinoma is unknown. The aims of this study were to determine if pre-treatment serum levels of uPAR forms and a decrease in levels during chemotherapy are predictive of survival in patients with inoperable cholangiocarcinoma. DESIGN AND METHODS: Patients with inoperable cholangiocarcinoma were consecutively included in the training set (n=108). A test set included patients from a different hospital using similar treatment guidelines (n=60). Serum levels of the different uPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for the uni- and multivariate survival analyses. RESULTS: Baseline level of uPAR(I-III)+uPAR(II-III) was an independent predictor of survival (HR=2.08, 95% CI:1.46-2.97, p<0.0001). Applying the linear predictor from the training set to the test set, it was validated that uPAR(I-III)+uPAR(II-III) predicted overall survival (p=0.049). A high level of uPAR(I-III)+uPAR(II-III) after 2cycles of chemotherapy was associated with poor survival (HR=1.79, 95% CI:1.08-2.97, p=0.023, n=57). This predictor, however, was not significant in the test set (p=0.21, 26 events in 27 patients). CONCLUSION: The baseline level of uPAR(I-III)+uPAR(II-III) is a predictor of survival in inoperable cholangiocarcinoma patients.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of circulating intact and cleaved forms of urokinase plasminogen activator receptor in inoperable chemotherapy treated cholangiocarcinoma patients BACKGROUND: High levels of intact and cleaved forms of the urokinase-type plasminogen activator receptor (uPAR) in both tissue and blood are associated with poor survival in several cancer diseases. The prognostic significance of uPAR in cholangiocarcinoma is unknown. The aims of this study were to determine if pre-treatment serum levels of uPAR forms and a decrease in levels during chemotherapy are predictive of survival in patients with inoperable cholangiocarcinoma. DESIGN AND METHODS: Patients with inoperable cholangiocarcinoma were consecutively included in the training set (n=108). A test set included patients from a different hospital using similar treatment guidelines (n=60). Serum levels of the different uPAR forms were determined using time-resolved fluorescence immunoassays (TR-FIA). The Cox proportional hazards model was used for the uni- and multivariate survival analyses. RESULTS: Baseline level of uPAR(I-III)+uPAR(II-III) was an independent predictor of survival (HR=2.08, 95% CI:1.46-2.97, p<0.0001). Applying the linear predictor from the training set to the test set, it was validated that uPAR(I-III)+uPAR(II-III) predicted overall survival (p=0.049). A high level of uPAR(I-III)+uPAR(II-III) after 2cycles of chemotherapy was associated with poor survival (HR=1.79, 95% CI:1.08-2.97, p=0.023, n=57). This predictor, however, was not significant in the test set (p=0.21, 26 events in 27 patients). CONCLUSION: The baseline level of uPAR(I-III)+uPAR(II-III) is a predictor of survival in inoperable cholangiocarcinoma patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"positive relationship number negative lymph nodes duration gallbladder cancer cause specific survival surgery background although prognostic implications negative lymph nodes nlns reported variety tumors little information published nlns gallbladder cancer gbc patients methods study clinicopathological characteristics survival times patients undergone surgery gbc collected surveillance epidemiology end results program registered tnm stage database analyzed univariate multivariate cox proportional hazards models used identify predictors survival results found cutoff one two nlns optimal assessing association survival survival rates consistently better two nlns fewer two optimal cutoff value 2 identified independent prognostic factor univariate multivariate analyses p 0 001 specifically patients two nlns better 5 year gallbladder cancer cause specific survival fewer nlns examined stage ii stage iii iv tnm stages p 0 001 conclusion findings indicate number nlns independent prognostic factor gbc surgery together number positive lymph nodes provide better prognostic information number positive lymph nodes alone stn","probabilities":0.9799733,"Title":"Positive Relationship Between Number Of Negative Lymph Nodes And Duration Of Gallbladder Cancer Cause-Specific Survival After Surgery","Abstract":"Background: Although the prognostic implications of negative lymph nodes (NLNs) has been reported for a variety of tumors, little information has been published about the NLNs in gallbladder cancer (GBC). \r\n\r\n Patients and methods: In this study, clinicopathological characteristics and survival times of patients who had undergone surgery for GBC were collected from the Surveillance, Epidemiology, and End Results Program-registered TNM stage database and analyzed. Univariate and multivariate Cox proportional hazards models were used to identify the predictors of survival. \r\n\r\n Results: It was found that a cutoff of one to two NLNs is optimal when assessing the association with survival, survival rates being consistently better with two or more NLNs than with fewer than two. This optimal cutoff value of 2 was identified as an independent prognostic factor by univariate and multivariate analyses (all P<0.001). Specifically, patients with two or more NLNs had better 5-year gallbladder cancer cause-specific survival than those with fewer than NLNs examined for stage I/II, stage III/IV, and all TNM stages (all P<0.001). \r\n\r\n Conclusion: Our findings indicate that the number of NLNs is an independent prognostic factor after GBC surgery, and, together with the number of positive lymph nodes, this will provide better prognostic information than the number of positive lymph nodes alone.","Source":"STN","category":"HUMAN","training_data":"Positive Relationship Between Number Of Negative Lymph Nodes And Duration Of Gallbladder Cancer Cause-Specific Survival After Surgery Background: Although the prognostic implications of negative lymph nodes (NLNs) has been reported for a variety of tumors, little information has been published about the NLNs in gallbladder cancer (GBC). \r\n\r\n Patients and methods: In this study, clinicopathological characteristics and survival times of patients who had undergone surgery for GBC were collected from the Surveillance, Epidemiology, and End Results Program-registered TNM stage database and analyzed. Univariate and multivariate Cox proportional hazards models were used to identify the predictors of survival. \r\n\r\n Results: It was found that a cutoff of one to two NLNs is optimal when assessing the association with survival, survival rates being consistently better with two or more NLNs than with fewer than two. This optimal cutoff value of 2 was identified as an independent prognostic factor by univariate and multivariate analyses (all P<0.001). Specifically, patients with two or more NLNs had better 5-year gallbladder cancer cause-specific survival than those with fewer than NLNs examined for stage I/II, stage III/IV, and all TNM stages (all P<0.001). \r\n\r\n Conclusion: Our findings indicate that the number of NLNs is an independent prognostic factor after GBC surgery, and, together with the number of positive lymph nodes, this will provide better prognostic information than the number of positive lymph nodes alone. STN","prediction_labels":"HUMAN"},{"cleaned":"resected biliary tract cancers novel clinical pathological score correlates global outcome background biliary tract cancer presents poor prognosis aims objective study find clinical laboratory parameters like prognostic factors select patients benefit surgery post operative treatments methods 2005 2010 41 patients underwent radical surgery institution novel score retrospectively calculated assigning grade clinical laboratory findings diagnosis 0 1 point respectively assigned normal abnormal parameter two groups identified score 0 score 1 results patients cholangiocarcinoma klatskin tumours asymptomatic diagnosis presented significantly better overall survival os patients different primary sites presented pain jaundice cholangitis univariate analysis high levels aspartate aminotransferase alanine aminotransferase ca19 9 surgery hyperbilirubinemia surgery negative correlation os worse os observed patients higher score median os score 0 group 30 79 months vs median os score 1 17 98 months conclusion results suggest pre post surgery clinical laboratory parameters novel score useful especially intrahepatic tumours predicting outcome patients undergoing surgery selecting patients receive adjuvant therapy pubmed","probabilities":0.9799733,"Title":"Resected biliary tract cancers: a novel clinical-pathological score correlates with global outcome","Abstract":"BACKGROUND: Biliary tract cancer presents a poor prognosis. AIMS: The objective of this study is to find clinical-laboratory parameters like prognostic factors to select patients who can benefit from surgery and post-operative treatments. METHODS: Between 2005 and 2010, 41 patients underwent radical surgery at our Institution. A novel score was retrospectively calculated assigning a grade to the clinical-laboratory findings at diagnosis. 0 and 1 point were respectively assigned to the normal or abnormal parameter. Two groups were identified: SCORE 0 and SCORE 1. RESULTS: Patients with cholangiocarcinoma or Klatskin tumours or asymptomatic at diagnosis presented a significantly better overall survival (OS) than patients with different primary sites or who presented pain, jaundice or cholangitis. At univariate analysis, high levels of aspartate aminotransferase, alanine aminotransferase and CA19-9 before surgery, hyperbilirubinemia before and after surgery had a negative correlation with OS. A worse OS was observed in patients with a higher score (median OS in the \"score 0\" group=30.79 months vs. median OS in the \"score 1\"=17.98 months). CONCLUSION: Our results suggest that pre and post-surgery clinical-laboratory parameters and the novel score, could be useful, especially for intrahepatic tumours, in predicting the outcome in patients undergoing surgery and in selecting patients to receive adjuvant therapy.","Source":"PubMed","category":"HUMAN","training_data":"Resected biliary tract cancers: a novel clinical-pathological score correlates with global outcome BACKGROUND: Biliary tract cancer presents a poor prognosis. AIMS: The objective of this study is to find clinical-laboratory parameters like prognostic factors to select patients who can benefit from surgery and post-operative treatments. METHODS: Between 2005 and 2010, 41 patients underwent radical surgery at our Institution. A novel score was retrospectively calculated assigning a grade to the clinical-laboratory findings at diagnosis. 0 and 1 point were respectively assigned to the normal or abnormal parameter. Two groups were identified: SCORE 0 and SCORE 1. RESULTS: Patients with cholangiocarcinoma or Klatskin tumours or asymptomatic at diagnosis presented a significantly better overall survival (OS) than patients with different primary sites or who presented pain, jaundice or cholangitis. At univariate analysis, high levels of aspartate aminotransferase, alanine aminotransferase and CA19-9 before surgery, hyperbilirubinemia before and after surgery had a negative correlation with OS. A worse OS was observed in patients with a higher score (median OS in the \"score 0\" group=30.79 months vs. median OS in the \"score 1\"=17.98 months). CONCLUSION: Our results suggest that pre and post-surgery clinical-laboratory parameters and the novel score, could be useful, especially for intrahepatic tumours, in predicting the outcome in patients undergoing surgery and in selecting patients to receive adjuvant therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"sociodemographic trends incidence pancreatic biliary tract cancer uk primary care background uk incidence pancreatic ductal adenocarcinoma pdac approximately 9 100 000 population compared 1 2 100 000 biliary tract cancer btc study explores incidence cancers time influence socio demographic geographic factors uk primary care cohort methods study uses data large uk primary care database health improvement network thin adult patients contributing data thin january 2000 december 2010 included annual incidence rates calculated adjusted age gender time period deprivation score townsend quintile strategic health authority results 2000 2010 annual incidence pdac increased average 3 per year 95 ci 1 00 4 00 btc 4 95 ci 2 00 6 00 incidence cancers increased steeply age higher men btc associated increasing deprivation deprived versus least deprived quintile 1 45 95 ci 1 17 1 79 conclusions overall incidence cancers low increasing variations incidence may reflect changes coding practice increased exposure associated risk factors stn","probabilities":0.9799733,"Title":"Sociodemographic Trends In The Incidence Of Pancreatic And Biliary Tract Cancer In Uk Primary Care","Abstract":"Background: The UK incidence of pancreatic ductal adenocarcinoma (PDAC) is approximately 9/100,000 population compared with 1-2/100,000 for biliary tract cancer (BTC). This study explores the incidence of these cancers over time and the influence of socio-demographic and geographic factors in a UK primary care cohort. \r\n\r\n Methods: This study uses data from a large UK primary care database, The Health Improvement Network (THIN). All adult patients contributing data to THIN between January 2000 and December 2010 were included. Annual incidence rates were calculated, adjusted for age, gender, time period, deprivation score (Townsend quintile) and strategic health authority. \r\n\r\n Results: From 2000-2010, the annual incidence of PDAC increased by an average of 3% per year (95% CI 1.00-4.00%) and BTC by 4% (95% CI 2.00-6.00%). Incidence of both cancers increased steeply with age and was higher in men. BTC was associated with increasing deprivation (most deprived versus least deprived quintile (OR: 1.45 [95% CI: 1.17, 1.79.]). \r\n\r\n Conclusions: The overall incidence of both cancers is low but increasing. Variations in incidence may reflect changes in coding practice or increased exposure to associated risk factors.","Source":"STN","category":"HUMAN","training_data":"Sociodemographic Trends In The Incidence Of Pancreatic And Biliary Tract Cancer In Uk Primary Care Background: The UK incidence of pancreatic ductal adenocarcinoma (PDAC) is approximately 9/100,000 population compared with 1-2/100,000 for biliary tract cancer (BTC). This study explores the incidence of these cancers over time and the influence of socio-demographic and geographic factors in a UK primary care cohort. \r\n\r\n Methods: This study uses data from a large UK primary care database, The Health Improvement Network (THIN). All adult patients contributing data to THIN between January 2000 and December 2010 were included. Annual incidence rates were calculated, adjusted for age, gender, time period, deprivation score (Townsend quintile) and strategic health authority. \r\n\r\n Results: From 2000-2010, the annual incidence of PDAC increased by an average of 3% per year (95% CI 1.00-4.00%) and BTC by 4% (95% CI 2.00-6.00%). Incidence of both cancers increased steeply with age and was higher in men. BTC was associated with increasing deprivation (most deprived versus least deprived quintile (OR: 1.45 [95% CI: 1.17, 1.79.]). \r\n\r\n Conclusions: The overall incidence of both cancers is low but increasing. Variations in incidence may reflect changes in coding practice or increased exposure to associated risk factors. STN","prediction_labels":"HUMAN"},{"cleaned":"novel serum marker biliary tract cancer diagnostic prognostic values quantitative evaluation serum mucin 5ac muc5ac background aims mucin 5ac muc5ac glycoprotein found different epithelial cancers including biliary tract cancer btc aims study investigate role muc5ac serum marker btc prognostic value operation curative intent patients method january 2007 july 2012 quantitative assessment serum muc5ac performed enzyme linked immunoassay total 88 subjects clinical biochemical data including cea ca 19 9 49 patients btc compared control population included 23 patients benign biliary disease bbd 16 healthy control subjects hcs results serum muc5ac greater btc patients mean 17 93 10 39 ng ml compared bbd mean 5 95 5 39 ng ml p 01 hcs mean 2 74 1 35 ng ml p 01 multivariate analysis showed muc5ac related presence btc compared ca 19 9 cea p 01 p 080 p 463 respectively btc group serum muc5ac 14 ng ml associated lymph node metastasis p 050 american joint committee cancer international union cancer control stage ivb disease p 047 moreover patients underwent operation curative intent serum muc5ac 14 ng ml related worse prognosis compared patients lesser levels 3 year survival rates 21 5 59 3 respectively p 039 conclusion muc5ac proposed new serum marker btc moreover quantitative assessment serum muc5ac related tumor stage long term survival patients btc undergoing operation curative intent pubmed","probabilities":0.9799733,"Title":"A novel serum marker for biliary tract cancer: diagnostic and prognostic values of quantitative evaluation of serum mucin 5AC (MUC5AC)","Abstract":"BACKGROUND AND AIMS: Mucin 5AC (MUC5AC) is a glycoprotein found in different epithelial cancers, including biliary tract cancer (BTC). The aims of this study were to investigate the role of MUC5AC as serum marker for BTC and its prognostic value after operation with curative intent. PATIENTS AND METHOD: From January 2007 to July 2012, a quantitative assessment of serum MUC5AC was performed with enzyme-linked immunoassay in a total of 88 subjects. Clinical and biochemical data (including CEA and Ca 19-9) of 49 patients with BTC were compared with a control population that included 23 patients with benign biliary disease (BBD) and 16 healthy control subjects (HCS). RESULTS: Serum MUC5AC was greater in BTC patients (mean 17.93 ± 10.39 ng/mL) compared with BBD (mean 5.95 ± 5.39 ng/mL; P < .01) and HCS (mean 2.74 ± 1.35 ng/mL) (P < .01). Multivariate analysis showed that MUC5AC was related with the presence of BTC compared with Ca 19-9 and CEA: P < .01, P = .080, and P = .463, respectively. In the BTC group, serum MUC5AC ≥ 14 ng/mL was associated with lymph-node metastasis (P = .050) and American Joint Committee on Cancer and International Union for Cancer Control stage IVb disease (P = .047). Moreover, in patients who underwent operation with curative intent, serum MUC5AC ≥ 14 ng/mL was related to a worse prognosis compared with patients with lesser levels, with 3-year survival rates of 21.5% and 59.3%, respectively (P = .039). CONCLUSION: MUC5AC could be proposed as new serum marker for BTC. Moreover, the quantitative assessment of serum MUC5AC could be related to tumor stage and long-term survival in patients with BTC undergoing operation with curative intent.","Source":"PubMed","category":"HUMAN","training_data":"A novel serum marker for biliary tract cancer: diagnostic and prognostic values of quantitative evaluation of serum mucin 5AC (MUC5AC) BACKGROUND AND AIMS: Mucin 5AC (MUC5AC) is a glycoprotein found in different epithelial cancers, including biliary tract cancer (BTC). The aims of this study were to investigate the role of MUC5AC as serum marker for BTC and its prognostic value after operation with curative intent. PATIENTS AND METHOD: From January 2007 to July 2012, a quantitative assessment of serum MUC5AC was performed with enzyme-linked immunoassay in a total of 88 subjects. Clinical and biochemical data (including CEA and Ca 19-9) of 49 patients with BTC were compared with a control population that included 23 patients with benign biliary disease (BBD) and 16 healthy control subjects (HCS). RESULTS: Serum MUC5AC was greater in BTC patients (mean 17.93 ± 10.39 ng/mL) compared with BBD (mean 5.95 ± 5.39 ng/mL; P < .01) and HCS (mean 2.74 ± 1.35 ng/mL) (P < .01). Multivariate analysis showed that MUC5AC was related with the presence of BTC compared with Ca 19-9 and CEA: P < .01, P = .080, and P = .463, respectively. In the BTC group, serum MUC5AC ≥ 14 ng/mL was associated with lymph-node metastasis (P = .050) and American Joint Committee on Cancer and International Union for Cancer Control stage IVb disease (P = .047). Moreover, in patients who underwent operation with curative intent, serum MUC5AC ≥ 14 ng/mL was related to a worse prognosis compared with patients with lesser levels, with 3-year survival rates of 21.5% and 59.3%, respectively (P = .039). CONCLUSION: MUC5AC could be proposed as new serum marker for BTC. Moreover, the quantitative assessment of serum MUC5AC could be related to tumor stage and long-term survival in patients with BTC undergoing operation with curative intent. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pyruvate kinase m2 novel diagnostic marker predicts tumor progression human biliary tract cancer background early diagnosis biliary tract cancer btc remains challenging effective therapies study investigated whether m2 isotype pyruvate kinase m2 pk serves key regulator cellular energy metabolism proliferating cells play role diagnosis therapy btc methods plasma bile m2 pk concentrations measured enzyme linked immunosorbent assay 88 patients btc 79 benign biliary diseases 17 healthy controls m2 pk expression assayed btc tissue array immunohistochemistry role m2 pk tumor growth invasion angiogenesis evaluated btc cell lines retrovirus mediated m2 pk transfection short hairpin rna silencing techniques results sensitivity 90 3 specificity 84 3 bile m2 pk malignancy significantly higher plasma m2 pk serum carbohydrate antigen 19 9 m2 pk expression specific cancer cells correlated microvessel density m2 pk positivity significant independent prognostic factor multivariable analysis transfection m2 pk negatively expressed cell line hucct 1 cells increased cell invasion whereas silencing m2 pk positive cell line tfk cells decreased tumor nodule formation cellular invasion significant increase endothelial tube formation noted supernatants m2 pk transfected cells added vitro angiogenesis assay whereas supernatants silenced cells negated endothelial tube formation conclusions bile m2 pk novel tumor marker btc correlates tumor aggressiveness poor outcome short hairpin rna mediated inhibition m2 pk indicates potential m2 pk therapeutic target pubmed","probabilities":1.0,"Title":"Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in human biliary tract cancer","Abstract":"BACKGROUND: The early diagnosis of biliary tract cancer (BTC) remains challenging, and there are few effective therapies. This study investigated whether the M2 isotype of pyruvate kinase (M2-PK), which serves as the key regulator of cellular energy metabolism in proliferating cells, could play a role in the diagnosis and therapy of BTC. METHODS: Plasma and bile M2-PK concentrations were measured by enzyme-linked immunosorbent assay in 88 patients with BTC, 79 with benign biliary diseases, and 17 healthy controls. M2-PK expression was assayed in a BTC tissue array by immunohistochemistry. The role of M2-PK in tumor growth, invasion, and angiogenesis was evaluated in BTC cell lines by retrovirus-mediated M2-PK transfection and short hairpin RNA silencing techniques. RESULTS: Sensitivity (90.3%) and specificity (84.3%) of bile M2-PK for malignancy were significantly higher than those for plasma M2-PK and serum carbohydrate antigen 19-9. M2-PK expression was specific for cancer cells and correlated with microvessel density. M2-PK positivity was a significant independent prognostic factor by multivariable analysis. Transfection of M2-PK in a negatively expressed cell line (HuCCT-1 cells) increased cell invasion, whereas silencing in an M2-PK-positive cell line (TFK cells) decreased tumor nodule formation and cellular invasion. A significant increase in endothelial tube formation was noted when supernatants from M2-PK-transfected cells were added to an in vitro angiogenesis assay, whereas supernatants from silenced cells negated endothelial tube formation. CONCLUSIONS: Bile M2-PK is a novel tumor marker for BTC and correlates with tumor aggressiveness and poor outcome. Short hairpin RNA-mediated inhibition of M2-PK indicates the potential of M2-PK as a therapeutic target.","Source":"PubMed","category":"HUMAN","training_data":"Pyruvate kinase M2 is a novel diagnostic marker and predicts tumor progression in human biliary tract cancer BACKGROUND: The early diagnosis of biliary tract cancer (BTC) remains challenging, and there are few effective therapies. This study investigated whether the M2 isotype of pyruvate kinase (M2-PK), which serves as the key regulator of cellular energy metabolism in proliferating cells, could play a role in the diagnosis and therapy of BTC. METHODS: Plasma and bile M2-PK concentrations were measured by enzyme-linked immunosorbent assay in 88 patients with BTC, 79 with benign biliary diseases, and 17 healthy controls. M2-PK expression was assayed in a BTC tissue array by immunohistochemistry. The role of M2-PK in tumor growth, invasion, and angiogenesis was evaluated in BTC cell lines by retrovirus-mediated M2-PK transfection and short hairpin RNA silencing techniques. RESULTS: Sensitivity (90.3%) and specificity (84.3%) of bile M2-PK for malignancy were significantly higher than those for plasma M2-PK and serum carbohydrate antigen 19-9. M2-PK expression was specific for cancer cells and correlated with microvessel density. M2-PK positivity was a significant independent prognostic factor by multivariable analysis. Transfection of M2-PK in a negatively expressed cell line (HuCCT-1 cells) increased cell invasion, whereas silencing in an M2-PK-positive cell line (TFK cells) decreased tumor nodule formation and cellular invasion. A significant increase in endothelial tube formation was noted when supernatants from M2-PK-transfected cells were added to an in vitro angiogenesis assay, whereas supernatants from silenced cells negated endothelial tube formation. CONCLUSIONS: Bile M2-PK is a novel tumor marker for BTC and correlates with tumor aggressiveness and poor outcome. Short hairpin RNA-mediated inhibition of M2-PK indicates the potential of M2-PK as a therapeutic target. PubMed","prediction_labels":"HUMAN"},{"cleaned":"histomorphologic spectrum bap1 negative melanocytic neoplasms family bap1 associated cancer susceptibility syndrome background multiple bap1 negative melanocytic neoplasms hallmark familial cancer susceptibility syndrome caused bap1 germline mutation syndrome characterized increased incidence renal cell carcinoma mesothelioma cholangiocarcinoma cutaneous uveal melanoma neoplasms methods report histomorphologic characteristics six cutaneous melanocytic neoplasms loss bap1 expression two members family bap1 associated cancer susceptibility syndrome results neoplasms dermal melanocytic nevi characterized proliferation large epithelioid spitzoid melanocytes adipocytic metaplasia nuclear pseudoinclusions multinucleated melanocytes present neoplasms two cases nodular melanoma found associated dermal nevus none melanomas recurred metastasized 6 3 years follow conclusions report two new cases melanoma arising bap1 deficient melanocytic nevus setting familial tumor predisposition syndrome adipocytic metaplasia nuclear pseudoinclusions may additional morphologic clues bap1 deficient nevus remains seen whether features common familial sporadic lesions google scholar","probabilities":0.9467213,"Title":"Histomorphologic Spectrum Of Bap1 Negative Melanocytic Neoplasms In A Family With Bap1-Associated Cancer Susceptibility Syndrome","Abstract":"Background\nMultiple BAP1 negative melanocytic neoplasms are a hallmark of familial cancer susceptibility syndrome caused by BAP1 germline mutation. The syndrome is characterized by increased incidence of renal cell carcinoma, mesothelioma, cholangiocarcinoma, cutaneous and uveal melanoma and some other neoplasms. \nMethods\nWe report histomorphologic characteristics of six cutaneous melanocytic neoplasms with loss of BAP1 expression in two members of a family with BAP1 ‐associated cancer susceptibility syndrome. \nResults\nThe neoplasms were dermal melanocytic nevi characterized by a proliferation of large epithelioid (spitzoid) melanocytes, and adipocytic metaplasia. Nuclear pseudoinclusions and multinucleated melanocytes were present in most neoplasms. In two of the cases, a nodular melanoma was found associated with a dermal nevus. None of the melanomas recurred or metastasized after 6 and 3 years of follow up.\nConclusions\nWe report two new cases of melanoma arising in a BAP1 ‐deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1 ‐deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions.","Source":"Google Scholar","category":"HUMAN","training_data":"Histomorphologic Spectrum Of Bap1 Negative Melanocytic Neoplasms In A Family With Bap1-Associated Cancer Susceptibility Syndrome Background\nMultiple BAP1 negative melanocytic neoplasms are a hallmark of familial cancer susceptibility syndrome caused by BAP1 germline mutation. The syndrome is characterized by increased incidence of renal cell carcinoma, mesothelioma, cholangiocarcinoma, cutaneous and uveal melanoma and some other neoplasms. \nMethods\nWe report histomorphologic characteristics of six cutaneous melanocytic neoplasms with loss of BAP1 expression in two members of a family with BAP1 ‐associated cancer susceptibility syndrome. \nResults\nThe neoplasms were dermal melanocytic nevi characterized by a proliferation of large epithelioid (spitzoid) melanocytes, and adipocytic metaplasia. Nuclear pseudoinclusions and multinucleated melanocytes were present in most neoplasms. In two of the cases, a nodular melanoma was found associated with a dermal nevus. None of the melanomas recurred or metastasized after 6 and 3 years of follow up.\nConclusions\nWe report two new cases of melanoma arising in a BAP1 ‐deficient melanocytic nevus in the setting of familial tumor predisposition syndrome. Adipocytic metaplasia and nuclear pseudoinclusions may be additional morphologic clues to a BAP1 ‐deficient nevus. It remains to be seen whether these features are more common in familial than sporadic lesions. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"major hepatopancreatoduodenectomy simultaneous resection hepatic artery advanced biliary cancer background major hepatopancreatoduodenectomy hpd simultaneous resection hepatic artery ha biliary cancer extended surgery obtaining curative resection clinical significance unclear aim study appraise clinical value extended procedure treatment biliary cancer methods retrospectively reviewed medical records 38 patients biliary cancer underwent major hpd 1994 2014 clinicopathological factors survival following hpd compared patients without simultaneous resection ha results 38 study patients 12 patients 32 underwent major hpd ha significant difference major complications two groups overall 2 year survival rate median survival time following major hpd ha 71 42 3 months survival patients gallbladder cancer significantly worse patients bile duct cancer p 0 001 conclusions major hpd simultaneous resection ha preferable treatment option bile duct cancer offers acceptable perioperative morbidity mortality well long term survival however procedure gallbladder cancer performed pubmed","probabilities":0.9799733,"Title":"Major hepatopancreatoduodenectomy with simultaneous resection of the hepatic artery for advanced biliary cancer","Abstract":"BACKGROUND: Major hepatopancreatoduodenectomy (HPD) with simultaneous resection of the hepatic artery (HA) for biliary cancer is the most extended surgery for obtaining curative resection, and its clinical significance is unclear. The aim of this study was to appraise the clinical value of this extended procedure as a treatment for biliary cancer. METHODS: We retrospectively reviewed the medical records of 38 patients with biliary cancer who underwent major HPD from 1994 to 2014. Clinicopathological factors and survival following HPD were compared between patients with and without simultaneous resection of the HA. RESULTS: Of the 38 study patients, 12 patients (32 %) underwent major HPD with HA. There was no significant difference in major complications between the two groups. The overall 2-year survival rate and the median survival time following major HPD with HA were 71 % and 42.3 months. The survival of the patients with gallbladder cancer was significantly worse than that of the patients with bile duct cancer (p = 0.001). CONCLUSIONS: Major HPD with simultaneous resection of the HA can be a preferable treatment option for bile duct cancer that offers acceptable perioperative morbidity and mortality, as well as long-term survival. However, this procedure for gallbladder cancer should not be performed.","Source":"PubMed","category":"HUMAN","training_data":"Major hepatopancreatoduodenectomy with simultaneous resection of the hepatic artery for advanced biliary cancer BACKGROUND: Major hepatopancreatoduodenectomy (HPD) with simultaneous resection of the hepatic artery (HA) for biliary cancer is the most extended surgery for obtaining curative resection, and its clinical significance is unclear. The aim of this study was to appraise the clinical value of this extended procedure as a treatment for biliary cancer. METHODS: We retrospectively reviewed the medical records of 38 patients with biliary cancer who underwent major HPD from 1994 to 2014. Clinicopathological factors and survival following HPD were compared between patients with and without simultaneous resection of the HA. RESULTS: Of the 38 study patients, 12 patients (32 %) underwent major HPD with HA. There was no significant difference in major complications between the two groups. The overall 2-year survival rate and the median survival time following major HPD with HA were 71 % and 42.3 months. The survival of the patients with gallbladder cancer was significantly worse than that of the patients with bile duct cancer (p = 0.001). CONCLUSIONS: Major HPD with simultaneous resection of the HA can be a preferable treatment option for bile duct cancer that offers acceptable perioperative morbidity and mortality, as well as long-term survival. However, this procedure for gallbladder cancer should not be performed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"imaging features predict prognosis patients combined hepatocellular cholangiocarcinoma aim evaluate prognostic value imaging patterns combined hepatocellular cholangiocarcinoma materials methods total 36 patients histopathologically confirmed combined hepatocellular cholangiocarcinoma enrolled pretreatment imaging conducted evaluate tumour enhancement patterns based disease classified two subtypes radiographic hepatocellular carcinoma dominant n 26 radiographic cholangiocarcinoma dominant n 10 moreover based proportion components combined hepatocellular cholangiocarcinoma cases divided histopathological hepatocellular carcinoma dominant n 26 histopathological cholangiocarcinoma dominant n 10 kaplan meier method used compare patient outcome two subtypes classification univariate cox regression analysis employed evaluate prognostic relevance imaging histopathological classification results consistency histopathological imaging classification high 66 7 patients consistent classification moreover median overall survival radiographic cholangiocarcinoma dominant radiographic hepatocellular carcinoma dominant population 15 03 40 4 months respectively p 0 012 however significant difference observed histopathological type median overall survival 32 07 40 4 months histopathological cholangiocarcinoma dominant group histopathological hepatocellular carcinoma dominant group respectively p 0 784 conclusion association imaging patterns overall survival combined hepatocellular cholangiocarcinoma postoperative re evaluation imaging patterns help assess patient outcome google scholar","probabilities":0.9799733,"Title":"Imaging Features Predict Prognosis Of Patients With Combined Hepatocellular-Cholangiocarcinoma","Abstract":"Aim\nTo evaluate the prognostic value of imaging patterns in combined hepatocellular-cholangiocarcinoma.\nMaterials and methods\nA total of 36 patients with histopathologically confirmed combined hepatocellular-cholangiocarcinoma were enrolled. Pretreatment imaging was conducted to evaluate the tumour enhancement patterns, based on which the disease was classified as two subtypes: radiographic hepatocellular carcinoma-dominant (n=26) and radiographic cholangiocarcinoma-dominant (n=10). Moreover, based on the proportion of components, all combined hepatocellular-cholangiocarcinoma cases were divided into histopathological hepatocellular carcinoma-dominant (n=26) or histopathological cholangiocarcinoma-dominant (n=10). The Kaplan–Meier method was used to compare patient outcome between the two subtypes of each classification. Univariate Cox regression analysis were employed to evaluate the prognostic relevance of the imaging and histopathological classification.\nResults\nConsistency between histopathological and imaging classification was not high. Only 66.7% of patients had consistent classification. Moreover, the median overall survival of the radiographic cholangiocarcinoma-dominant and radiographic hepatocellular carcinoma-dominant population was 15.03 and 40.4 months, respectively (p=0.012); however, no significant difference was observed between histopathological type, with median overall survival being 32.07 and 40.4 months in the histopathological cholangiocarcinoma-dominant group and histopathological hepatocellular carcinoma-dominant group, respectively (p=0.784).\nConclusion\nThere was an association between imaging patterns and overall survival in combined hepatocellular-cholangiocarcinoma. Postoperative re-evaluation of imaging patterns could help to assess patient outcome.","Source":"Google Scholar","category":"HUMAN","training_data":"Imaging Features Predict Prognosis Of Patients With Combined Hepatocellular-Cholangiocarcinoma Aim\nTo evaluate the prognostic value of imaging patterns in combined hepatocellular-cholangiocarcinoma.\nMaterials and methods\nA total of 36 patients with histopathologically confirmed combined hepatocellular-cholangiocarcinoma were enrolled. Pretreatment imaging was conducted to evaluate the tumour enhancement patterns, based on which the disease was classified as two subtypes: radiographic hepatocellular carcinoma-dominant (n=26) and radiographic cholangiocarcinoma-dominant (n=10). Moreover, based on the proportion of components, all combined hepatocellular-cholangiocarcinoma cases were divided into histopathological hepatocellular carcinoma-dominant (n=26) or histopathological cholangiocarcinoma-dominant (n=10). The Kaplan–Meier method was used to compare patient outcome between the two subtypes of each classification. Univariate Cox regression analysis were employed to evaluate the prognostic relevance of the imaging and histopathological classification.\nResults\nConsistency between histopathological and imaging classification was not high. Only 66.7% of patients had consistent classification. Moreover, the median overall survival of the radiographic cholangiocarcinoma-dominant and radiographic hepatocellular carcinoma-dominant population was 15.03 and 40.4 months, respectively (p=0.012); however, no significant difference was observed between histopathological type, with median overall survival being 32.07 and 40.4 months in the histopathological cholangiocarcinoma-dominant group and histopathological hepatocellular carcinoma-dominant group, respectively (p=0.784).\nConclusion\nThere was an association between imaging patterns and overall survival in combined hepatocellular-cholangiocarcinoma. Postoperative re-evaluation of imaging patterns could help to assess patient outcome. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"diabetes mellitus risk factor intrahepatic extrahepatic cholangiocarcinoma meta analysis case control studies background diabetes mellitus dm associated increased risk several cancers including gastrointestinal cancers recent studies reported dm possible risk factor biliary tract cancers conducted meta analysis case control studies assess risk intrahepatic icc extrahepatic cholangiocarcinoma ecc aim quantifythe riskoficcand eccinpatientswith dm methods performedasystematic searchofmedline embaseandthecochranelibraryforstudieswithoutlanguagerestriction case control studies evaluating risk intrahepatic extrahepatic cholangiocarcinoma adult patients diabetes mellitus search date 11 2010 also hand searched greyliterature frommajor gastrointestinalmeetings standardizedforms wereusedto extract dataregardingnumberofcasesofdiabetes intrahepaticcholangiocarcinomaandextrahepatic cholangiocarcinoma data extracted two reviewers independently summary odds ratiowascalculatedusingcomprehensivemeta analysissoftware heterogeneityandpublication bias also assessed random effects model used pooling data results seven studies 3219 icc cases 237208 controls evaluated risk icc 4 studies 1202 ecc cases 127041 controls evaluated risk ecc patients dm studies werepublished fromus europeand asia populationbased controlswere usedin 3studies risk icc dm higher non diabetic patients 1 91 95 ci 1 492 46 p 0 005 analysis studies western countries revealed increased odds oficc 1 81 95 ci 1 6 2 05 dm howeverodds notsignificantly increased among asian countries 1 76 95 ci 0 73 4 20 p 0 21 difference noted among studies using either population based controls hospital based controls odds ecc dm also increased 1 58 95 ci 1 35 1 86 p 0 0001 increased risk seen western asian countries significant heterogeneity present among studies thus data analyzed random effects model conclusion diabetesmellitusisassociatedanincreasedriskofbothintra andextrahepaticcholangiocarcinoma theincreasedriskoficcwasseeninthewesterncountriesbutnotasiancountries cohort studies needed confirm association google scholar","probabilities":0.9799733,"Title":"Is Diabetes Mellitus A Risk Factor For Intrahepatic And Extrahepatic Cholangiocarcinoma?: A Meta-Analysis Of Case Control Studies","Abstract":"Background : Diabetes mellitus (DM) has been associated with increased risk of several cancers, including gastrointestinal cancers. Recent studies have reported DM as a possible risk factor for biliary tract cancers. We conducted a meta-analysis of case control studies to assess the risk of intrahepatic (ICC) and extrahepatic cholangiocarcinoma (ECC). Aim: To quantifythe riskofICCand ECCinpatientswith DM.Methods:We performedasystematic searchofMedline,EMBASEandtheCochraneLibraryforstudieswithoutlanguagerestriction for case control studies evaluating the risk of intrahepatic and extrahepatic cholangiocarcinoma in adult patients with diabetes mellitus (search date 11/2010). We also hand searched greyliterature frommajor gastrointestinalmeetings. Standardizedforms wereusedto extract dataregardingnumberofcasesofdiabetes,intrahepaticcholangiocarcinomaandextrahepatic cholangiocarcinoma. Data was extracted by two reviewers independently. Summary odds ratiowascalculatedusingComprehensiveMeta-analysissoftware.Heterogeneityandpublication bias were also assessed. Random effects model was used for pooling the data. Results : Seven studies (3219 ICC cases/ 237208 controls) evaluated the risk of ICC while 4 studies (1202 ECC cases/ 127041 Controls) evaluated the risk of ECC in patients with DM. Studies werepublished fromUS, Europeand Asia.Populationbased controlswere usedin 3studies. The risk of ICC in DM was higher than non-diabetic patients ( OR 1.91 :95% CI: 1.492.46, p< 0.005). Analysis of the studies from the Western countries revealed an increased odds ofICC ( 1.81:95% CI, 1.6-2.05)in DM, howeverodds were notsignificantly increased among Asian countries ( OR 1.76: (95% CI, 0.73-4.20, p=0.21). No difference was noted among studies using either population based controls or hospital based controls. The odds of ECC in DM was also increased ( OR 1.58, 95% CI: 1.35-1.86, p< 0.0001). The increased risk was seen both in Western and Asian countries. Significant heterogeneity was present among the studies and thus the data was analyzed by random effects model. Conclusion: DiabetesMellitusisassociatedanincreasedriskofbothintra-andextrahepaticcholangiocarcinoma.TheincreasedriskofICCwasseenintheWesterncountriesbutnotAsiancountries. Cohort studies are needed to confirm this association.","Source":"Google Scholar","category":"HUMAN","training_data":"Is Diabetes Mellitus A Risk Factor For Intrahepatic And Extrahepatic Cholangiocarcinoma?: A Meta-Analysis Of Case Control Studies Background : Diabetes mellitus (DM) has been associated with increased risk of several cancers, including gastrointestinal cancers. Recent studies have reported DM as a possible risk factor for biliary tract cancers. We conducted a meta-analysis of case control studies to assess the risk of intrahepatic (ICC) and extrahepatic cholangiocarcinoma (ECC). Aim: To quantifythe riskofICCand ECCinpatientswith DM.Methods:We performedasystematic searchofMedline,EMBASEandtheCochraneLibraryforstudieswithoutlanguagerestriction for case control studies evaluating the risk of intrahepatic and extrahepatic cholangiocarcinoma in adult patients with diabetes mellitus (search date 11/2010). We also hand searched greyliterature frommajor gastrointestinalmeetings. Standardizedforms wereusedto extract dataregardingnumberofcasesofdiabetes,intrahepaticcholangiocarcinomaandextrahepatic cholangiocarcinoma. Data was extracted by two reviewers independently. Summary odds ratiowascalculatedusingComprehensiveMeta-analysissoftware.Heterogeneityandpublication bias were also assessed. Random effects model was used for pooling the data. Results : Seven studies (3219 ICC cases/ 237208 controls) evaluated the risk of ICC while 4 studies (1202 ECC cases/ 127041 Controls) evaluated the risk of ECC in patients with DM. Studies werepublished fromUS, Europeand Asia.Populationbased controlswere usedin 3studies. The risk of ICC in DM was higher than non-diabetic patients ( OR 1.91 :95% CI: 1.492.46, p< 0.005). Analysis of the studies from the Western countries revealed an increased odds ofICC ( 1.81:95% CI, 1.6-2.05)in DM, howeverodds were notsignificantly increased among Asian countries ( OR 1.76: (95% CI, 0.73-4.20, p=0.21). No difference was noted among studies using either population based controls or hospital based controls. The odds of ECC in DM was also increased ( OR 1.58, 95% CI: 1.35-1.86, p< 0.0001). The increased risk was seen both in Western and Asian countries. Significant heterogeneity was present among the studies and thus the data was analyzed by random effects model. Conclusion: DiabetesMellitusisassociatedanincreasedriskofbothintra-andextrahepaticcholangiocarcinoma.TheincreasedriskofICCwasseenintheWesterncountriesbutnotAsiancountries. Cohort studies are needed to confirm this association. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"treatment cholangiocarcinoma bromelain papain cholangiocarcinoma cc worldwide common biliary malignancy poor prognostic value new systemic treatments desirable plant extracts like bromelain papain cysteine proteases fruit pineapple papaya known antitumor activities therefore study first time investigated anticancer effect bromelain papain intra extrahepatic human cc cell lines effect bromelain papain human cc cell growth migration invasion epithelial plasticity analyzed using cell proliferation wound healing invasion apoptosis assay well western blotting bromelain papain lead decrease proliferation invasion migration cc cells plant extracts inhibited nf b ampk signalling well downstream signalling proteins p akt p erk p stat3 additionally mmp9 epithelial mesenchymal transition markers partially found downregulated apoptosis induced bromelain papain treatment interestingly bromelain showed overall effective inhibition cc compared papain sirna mediated silencing nf b cc cells indicated bromelain papain cytotoxic effects human cc cell lines bromelain partially papain comparison impair tumor growth nf b ampk signalling especially bromelain evolve promising potential therapeutic option might open new insights treatment human cc stn","probabilities":0.9467213,"Title":"Treatment Of Cholangiocarcinoma By Bromelain And Papain","Abstract":"Cholangiocarcinoma (CC) worldwide is the most common biliary malignancy with poor prognostic value and new systemic treatments are desirable. Plant extracts like bromelain and papain, which are cysteine proteases from the fruit pineapple and papaya, are known to have antitumor activities. Therefore, in this study for the first time we investigated the anticancer effect of bromelain and papain in intra- and extrahepatic human CC cell lines. The effect of bromelain and papain on human CC cell growth, migration, invasion and epithelial plasticity was analyzed using cell proliferation, wound healing, invasion and apoptosis assay, as well as western blotting. Bromelain and papain lead to a decrease in the proliferation, invasion and migration of CC cells. Both plant extracts inhibited NFκB/AMPK signalling as well as their downstream signalling proteins such as p-AKT, p-ERK, p-Stat3. Additionally, MMP9 and other epithelial-mesenchymal-transition markers were partially found to be downregulated. Apoptosis was induced after bromelain and papain treatment. Interestingly, bromelain showed an overall more effective inhibition of CC as compared to papain. siRNA mediated silencing of NFκB on CC cells indicated that bromelain and papain have cytotoxic effects on human CC cell lines and bromelain and partially papain in comparison impair tumor growth by NFκB/AMPK signalling. Especially bromelain can evolve as promising, potential therapeutic option that might open new insights for the treatment of human CC.","Source":"STN","category":"ANIMAL","training_data":"Treatment Of Cholangiocarcinoma By Bromelain And Papain Cholangiocarcinoma (CC) worldwide is the most common biliary malignancy with poor prognostic value and new systemic treatments are desirable. Plant extracts like bromelain and papain, which are cysteine proteases from the fruit pineapple and papaya, are known to have antitumor activities. Therefore, in this study for the first time we investigated the anticancer effect of bromelain and papain in intra- and extrahepatic human CC cell lines. The effect of bromelain and papain on human CC cell growth, migration, invasion and epithelial plasticity was analyzed using cell proliferation, wound healing, invasion and apoptosis assay, as well as western blotting. Bromelain and papain lead to a decrease in the proliferation, invasion and migration of CC cells. Both plant extracts inhibited NFκB/AMPK signalling as well as their downstream signalling proteins such as p-AKT, p-ERK, p-Stat3. Additionally, MMP9 and other epithelial-mesenchymal-transition markers were partially found to be downregulated. Apoptosis was induced after bromelain and papain treatment. Interestingly, bromelain showed an overall more effective inhibition of CC as compared to papain. siRNA mediated silencing of NFκB on CC cells indicated that bromelain and papain have cytotoxic effects on human CC cell lines and bromelain and partially papain in comparison impair tumor growth by NFκB/AMPK signalling. Especially bromelain can evolve as promising, potential therapeutic option that might open new insights for the treatment of human CC. STN","prediction_labels":"ANIMAL"},{"cleaned":"arterial infusion cisplatin plus 1 unresectable intrahepatic cholangiocarcinoma conventional regimens unresectable intrahepatic cholangiocarcinoma considered limited effectiveness evaluate efficacy toxicity combination chemotherapy hepatic arterial infusion ia call fine powder formulation cisplatin plus oral 1 patients unresectable intrahepatic cholangiocarcinoma clinicopathological data long term outcome 12 patients received ia call plus 1 compared 16 patients received treatments radiation therapy trans arterial chemoembolization systemic chemotherapy ia call plus 1 regimen consisted ia call 65 mg m2 administered hepatic artery day 1 oral 1 60 mg m2 day days 1 28 every 42 days repeated cycle prognostic factors patients evaluated uni multivariate analysis significant difference two groups disease status number tumor tumor size overall survival significantly longer patients receiving arterial ia call 1 regimen median survival time 10 1 range 3 6 24 2 months receiving treatments median survival time 4 0 range 0 3 24 2 months p 0 01 multivariate analysis revealed chemotherapy regimen significantly related survival hazard ratio 3 97 p 0 02 ia call plus 1 group overall response rate 33 3 major toxic effect grade 3 anemia occurring 1 patient 4 5 combination chemotherapy arterial ia call plus oral 1 effective regimen may improve survival patients unresectable intrahepatic cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Arterial Infusion Of Cisplatin Plus S-1 Against Unresectable Intrahepatic Cholangiocarcinoma","Abstract":"Conventional regimens for unresectable intrahepatic cholangiocarcinoma are considered of limited effectiveness. To evaluate the efficacy and toxicity of combination chemotherapy with hepatic arterial infusion of IA-call (a fine-powder formulation of cisplatin) plus oral S-1 in patients with unresectable intrahepatic cholangiocarcinoma. The clinicopathological data and long-term outcome of 12 patients who were received with IA-call plus S-1 were compared with those of 16 patients who were received other treatments, such as radiation therapy, trans-arterial chemoembolization, and systemic chemotherapy. The IA-call plus S-1 regimen consisted of IA-call (65 mg/m2, administered into the hepatic artery) on day 1 and oral S-1 (60 mg/m2/day) on days 1-28, every 42 days, repeated cycle. Prognostic factors of these patients were evaluated by uni- and multivariate analysis. There was no significant difference between the two groups in the disease status, such as the number of tumor and the tumor size. The overall survival was significantly longer in the patients receiving the arterial IA-call and S-1 regimen (median survival time = 10.1; range, 3.6-24.2 months) than in the receiving other treatments (median survival time = 4.0; range; 0.3-24.2 months, p = 0.01). The multivariate analysis revealed that chemotherapy regimen was significantly related to survival, with a hazard ratio of 3.97 (p = 0.02). In the IA-call plus S-1 group, the overall response rate was 33.3%. The major toxic effect was grade 3 anemia, occurring in 1 patient (4.5%). Combination chemotherapy with arterial IA-call plus oral S-1 is an effective regimen that may improve survival in patients with unresectable intrahepatic cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Arterial Infusion Of Cisplatin Plus S-1 Against Unresectable Intrahepatic Cholangiocarcinoma Conventional regimens for unresectable intrahepatic cholangiocarcinoma are considered of limited effectiveness. To evaluate the efficacy and toxicity of combination chemotherapy with hepatic arterial infusion of IA-call (a fine-powder formulation of cisplatin) plus oral S-1 in patients with unresectable intrahepatic cholangiocarcinoma. The clinicopathological data and long-term outcome of 12 patients who were received with IA-call plus S-1 were compared with those of 16 patients who were received other treatments, such as radiation therapy, trans-arterial chemoembolization, and systemic chemotherapy. The IA-call plus S-1 regimen consisted of IA-call (65 mg/m2, administered into the hepatic artery) on day 1 and oral S-1 (60 mg/m2/day) on days 1-28, every 42 days, repeated cycle. Prognostic factors of these patients were evaluated by uni- and multivariate analysis. There was no significant difference between the two groups in the disease status, such as the number of tumor and the tumor size. The overall survival was significantly longer in the patients receiving the arterial IA-call and S-1 regimen (median survival time = 10.1; range, 3.6-24.2 months) than in the receiving other treatments (median survival time = 4.0; range; 0.3-24.2 months, p = 0.01). The multivariate analysis revealed that chemotherapy regimen was significantly related to survival, with a hazard ratio of 3.97 (p = 0.02). In the IA-call plus S-1 group, the overall response rate was 33.3%. The major toxic effect was grade 3 anemia, occurring in 1 patient (4.5%). Combination chemotherapy with arterial IA-call plus oral S-1 is an effective regimen that may improve survival in patients with unresectable intrahepatic cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"endoscopic versus surgical ampullectomy algorithm treat disease ampulla vater objective objective study compare effectiveness morbidity mortality associated endoscopic ampullectomy ea surgical ampullectomy sa background proposed management benign ampullary lesions includes local resection ea sa en bloc resection pancreaticoduodenectomy agree en bloc resection entails significant morbidity mortality study previously compared ea sa treatment benign ampullary lesions methods medical records patients selected ampullectomy duke university medical center 1991 2010 reviewed results review 109 patients confirmed undergone ampullectomy suspected benign ampullary lesion sixty eight patients underwent ea whereas 41 patients underwent sa patients group identical terms age sex race comorbid conditions except ea higher rate severe obesity body mass index 35 endoscopic ampullectomy found significantly reduced length stay lower morbidity readmission rates similar rates mortality margin positive excisions reinterventions conclusions patients selected ampullectomy benign ampullary lesions ea found equivalent efficacy compared sa moreover ea lower morbidity identical mortality findings suggest patients likely benefit aggressive endoscopic approach consideration surgery pubmed","probabilities":0.9799733,"Title":"Endoscopic versus surgical ampullectomy: an algorithm to treat disease of the ampulla of Vater","Abstract":"OBJECTIVE: The objective of this study was to compare the effectiveness, morbidity, and mortality associated with endoscopic ampullectomy (EA) and surgical ampullectomy (SA). BACKGROUND: The proposed management of benign ampullary lesions includes local resection (EA or SA) and en bloc resection (pancreaticoduodenectomy). Most agree that en bloc resection entails a significant morbidity and mortality. No study has previously compared EA and SA for the treatment of benign ampullary lesions. METHODS: Medical records of patients selected for ampullectomy at Duke University Medical Center from 1991 to 2010 were reviewed. RESULTS: After review, 109 patients were confirmed to have undergone ampullectomy for a suspected benign ampullary lesion. Sixty-eight patients underwent EA, whereas 41 patients underwent SA. Patients in each group were identical in terms of age, sex, race, and comorbid conditions, except that EA had a higher rate of severe obesity (body mass index >35). Endoscopic ampullectomy was found to have a significantly reduced length of stay, lower morbidity, and readmission rates, but it had similar rates of mortality, margin-positive excisions, and reinterventions. CONCLUSIONS: In patients selected for ampullectomy for benign ampullary lesions, EA was found to have equivalent efficacy when compared with SA. Moreover, EA had lower morbidity and identical mortality. These findings suggest that patients would likely benefit from an aggressive endoscopic approach before consideration for surgery.","Source":"PubMed","category":"HUMAN","training_data":"Endoscopic versus surgical ampullectomy: an algorithm to treat disease of the ampulla of Vater OBJECTIVE: The objective of this study was to compare the effectiveness, morbidity, and mortality associated with endoscopic ampullectomy (EA) and surgical ampullectomy (SA). BACKGROUND: The proposed management of benign ampullary lesions includes local resection (EA or SA) and en bloc resection (pancreaticoduodenectomy). Most agree that en bloc resection entails a significant morbidity and mortality. No study has previously compared EA and SA for the treatment of benign ampullary lesions. METHODS: Medical records of patients selected for ampullectomy at Duke University Medical Center from 1991 to 2010 were reviewed. RESULTS: After review, 109 patients were confirmed to have undergone ampullectomy for a suspected benign ampullary lesion. Sixty-eight patients underwent EA, whereas 41 patients underwent SA. Patients in each group were identical in terms of age, sex, race, and comorbid conditions, except that EA had a higher rate of severe obesity (body mass index >35). Endoscopic ampullectomy was found to have a significantly reduced length of stay, lower morbidity, and readmission rates, but it had similar rates of mortality, margin-positive excisions, and reinterventions. CONCLUSIONS: In patients selected for ampullectomy for benign ampullary lesions, EA was found to have equivalent efficacy when compared with SA. Moreover, EA had lower morbidity and identical mortality. These findings suggest that patients would likely benefit from an aggressive endoscopic approach before consideration for surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression clinicopathological significance notch signaling cell fate genes biliary tract cancer objectives biliary tract cancer btc fatal cancer originating epithelial cells intra extra hepatic biliary duct system gallbladder genes pathways regulating stem progenitor cells well cell fate decisions increasingly recognized tumorigenesis evaluated expression notch1 notch2 hes1 hairy enhancer split 1 well biliary cell fate regulators sox9 sry sex determining region y box 9 hnf1 hepatocyte nuclear factor 1 btc correlation clinicopathological parameters methods tissue microarrays including normal bile ducts 111 btcs consisting 17 intrahepatic cholangiocarcinomas 58 extrahepatic cholangiocarcinomas 36 gallbladder carcinomas analyzed using immunohistochemistry results lack cytoplasmic sox9 expression associated higher tumor grade p 0 010 significantly reduced overall survival p 0 002 median 6 months vs 24 months univariate survival analysis whereas lack nuclear sox9 expression associated higher tumor stage p 0 003 notch pathway members showed high expression btc however correlation found cytoplasmic nuclear notch1 notch2 hes1 well hnf1 expression clinicopathological parameters multivariate analysis cytoplasmic sox9 expression independent prognostic factor overall survival p 0 031 relative risk 0 571 conclusions show strong notch pathway activation identify sox9 prognostic marker btc results substantiate diagnostic therapeutic approaches targeting developmentally active genes pathways pubmed","probabilities":0.962963,"Title":"Expression and clinicopathological significance of notch signaling and cell-fate genes in biliary tract cancer","Abstract":"OBJECTIVES: Biliary tract cancer (BTC) is a fatal cancer originating from epithelial cells of the intra- and extra-hepatic biliary duct system and the gallbladder. Genes and pathways regulating stem and progenitor cells as well as cell-fate decisions are increasingly recognized in tumorigenesis. We evaluated the expression of Notch1, Notch2, and HES1 (hairy and enhancer of split 1), as well as the biliary cell-fate regulators SOX9 (SRY (sex determining region Y)-box 9) and HNF1β (hepatocyte nuclear factor 1β), in BTC for correlation with clinicopathological parameters. METHODS: Tissue microarrays including normal bile ducts and 111 BTCs consisting of 17 intrahepatic cholangiocarcinomas, 58 extrahepatic cholangiocarcinomas, and 36 gallbladder carcinomas were analyzed using immunohistochemistry. RESULTS: Lack of cytoplasmic SOX9 expression was associated with a higher tumor grade (P=0.010) and a significantly reduced overall survival (P=0.002; median 6 months vs. 24 months) in univariate survival analysis, whereas lack of nuclear SOX9 expression was associated with a higher tumor stage (P=0.003). Notch pathway members showed high expression in BTC. However, no correlation was found between cytoplasmic or nuclear Notch1, Notch2, and HES1, as well as HNF1β expression, and any of the clinicopathological parameters. In multivariate analysis, cytoplasmic SOX9 expression was an independent prognostic factor for overall survival (P=0.031, relative risk=0.571). CONCLUSIONS: We show strong Notch pathway activation and identify SOX9 as a prognostic marker in BTC. These results substantiate diagnostic and therapeutic approaches targeting developmentally active genes and pathways.","Source":"PubMed","category":"HUMAN","training_data":"Expression and clinicopathological significance of notch signaling and cell-fate genes in biliary tract cancer OBJECTIVES: Biliary tract cancer (BTC) is a fatal cancer originating from epithelial cells of the intra- and extra-hepatic biliary duct system and the gallbladder. Genes and pathways regulating stem and progenitor cells as well as cell-fate decisions are increasingly recognized in tumorigenesis. We evaluated the expression of Notch1, Notch2, and HES1 (hairy and enhancer of split 1), as well as the biliary cell-fate regulators SOX9 (SRY (sex determining region Y)-box 9) and HNF1β (hepatocyte nuclear factor 1β), in BTC for correlation with clinicopathological parameters. METHODS: Tissue microarrays including normal bile ducts and 111 BTCs consisting of 17 intrahepatic cholangiocarcinomas, 58 extrahepatic cholangiocarcinomas, and 36 gallbladder carcinomas were analyzed using immunohistochemistry. RESULTS: Lack of cytoplasmic SOX9 expression was associated with a higher tumor grade (P=0.010) and a significantly reduced overall survival (P=0.002; median 6 months vs. 24 months) in univariate survival analysis, whereas lack of nuclear SOX9 expression was associated with a higher tumor stage (P=0.003). Notch pathway members showed high expression in BTC. However, no correlation was found between cytoplasmic or nuclear Notch1, Notch2, and HES1, as well as HNF1β expression, and any of the clinicopathological parameters. In multivariate analysis, cytoplasmic SOX9 expression was an independent prognostic factor for overall survival (P=0.031, relative risk=0.571). CONCLUSIONS: We show strong Notch pathway activation and identify SOX9 as a prognostic marker in BTC. These results substantiate diagnostic and therapeutic approaches targeting developmentally active genes and pathways. PubMed","prediction_labels":"HUMAN"},{"cleaned":"contemporary perspectives use radiation therapy locally advanced gallbladder cancer locally advanced gallbladder cancer poor prognosis due high distant metastatic rate poor overall disease control impact standard therapeutic options unfortunately modest due rarity disease evidence based management continues evolve goal review highlight contemporary landscape radiation therapy gallbladder cancer first rationale radiation therapy described includes risk locoregional recurrence following resection based patterns failure data along high locoregional disease burden frequent cause morbidity mortality unresected cases additionally improvements systemic therapy next decade shift contemporary patterns failure towards proportionally higher locoregional recurrence rates second clinical data radiation therapy gallbladder cancer discussed include consideration postoperative chemoradiotherapy margin node positive cases patients localized unresectable disease benefit ablative radiation therapy based promising data non gallbladder cancer pancreaticobiliary neoplasms use advanced radiation therapy technologies proton beam therapy means deliver ablative radiation therapy potentially safer manner also mentioned lastly emerging concept neoadjuvant therapy gallbladder cancer also described efforts allow patients receive curative resection pubmed","probabilities":0.9799733,"Title":"Contemporary perspectives on the use of radiation therapy for locally advanced gallbladder cancer","Abstract":"Locally advanced gallbladder cancer poor prognosis due to a high distant metastatic rate and poor overall disease control. The impact of standard therapeutic options is unfortunately modest. Due to the rarity of the disease, evidence-based management continues to evolve. The goal of this review is to highlight the contemporary landscape of radiation therapy for gallbladder cancer. First, the rationale for radiation therapy is described. This includes the risk of locoregional recurrence following resection based on patterns-of-failure data, along with the high locoregional disease burden being a frequent cause morbidity and mortality in unresected cases. Additionally, improvements in systemic therapy over the next decade could shift contemporary patterns of failure more towards proportionally higher locoregional recurrence rates. Second, clinical data of radiation therapy for gallbladder cancer are discussed. These include consideration of postoperative chemoradiotherapy for margin- and/or node-positive cases. Patients with localized unresectable disease could benefit from ablative radiation therapy, based on promising data in non-gallbladder cancer pancreaticobiliary neoplasms. The use of advanced radiation therapy technologies such as proton beam therapy, as a means to deliver ablative radiation therapy in a potentially safer manner, is also mentioned. Lastly, the emerging concept of neoadjuvant therapy for gallbladder cancer is also described, in efforts to allow more patients to receive curative resection.","Source":"PubMed","category":"HUMAN","training_data":"Contemporary perspectives on the use of radiation therapy for locally advanced gallbladder cancer Locally advanced gallbladder cancer poor prognosis due to a high distant metastatic rate and poor overall disease control. The impact of standard therapeutic options is unfortunately modest. Due to the rarity of the disease, evidence-based management continues to evolve. The goal of this review is to highlight the contemporary landscape of radiation therapy for gallbladder cancer. First, the rationale for radiation therapy is described. This includes the risk of locoregional recurrence following resection based on patterns-of-failure data, along with the high locoregional disease burden being a frequent cause morbidity and mortality in unresected cases. Additionally, improvements in systemic therapy over the next decade could shift contemporary patterns of failure more towards proportionally higher locoregional recurrence rates. Second, clinical data of radiation therapy for gallbladder cancer are discussed. These include consideration of postoperative chemoradiotherapy for margin- and/or node-positive cases. Patients with localized unresectable disease could benefit from ablative radiation therapy, based on promising data in non-gallbladder cancer pancreaticobiliary neoplasms. The use of advanced radiation therapy technologies such as proton beam therapy, as a means to deliver ablative radiation therapy in a potentially safer manner, is also mentioned. Lastly, the emerging concept of neoadjuvant therapy for gallbladder cancer is also described, in efforts to allow more patients to receive curative resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"differential expression fascin e cadherin vimentin proteins associated survival cholangiocarcinoma patients introduction study investigated differential expression fascin e cadherin vimentin human carcinogenesis methods study detected expressions 142 cholangiocarcinoma 20 benign bile duct tissue specimens using immunohistochemistry clinicopathologic characteristics survival data also collected analyzed association expression 3 proteins results data showed fascin vimentin proteins significantly overexpressed cholangiocarcinoma whereas e cadherin expression reduced cholangiocarcinoma compared normal tissues fascin protein expression associated tumor dedifferentiation venous invasion lymph node distant metastasis similarly vimentin expression associated tumor dedifferentiation venous invasion well hepatitis virus infection contrast loss e cadherin expression associated tumor dedifferentiation p 0 05 functions 3 proteins closely related data showed fascin e cadherin protein expression reversely associated however fascin vimentin protein expression positively associated cholangiocarcinoma cox multiple regression analysis showed distant tumor metastasis tumor differentiation overexpression fascin vimentin proteins independent risk factors prognosis p 0 05 conclusion data current study demonstrated overexpression fascin vimentin proteins evaluated biomarkers prediction cholangiocarcinoma patient survival stn","probabilities":0.8333333,"Title":"Differential Expression Of Fascin E-Cadherin And Vimentin: Proteins Associated With Survival Of Cholangiocarcinoma Patients","Abstract":"Introduction: This study investigated the differential expression of fascin, E-cadherin and vimentin in human carcinogenesis. \r\n\r\n Methods: This study detected their expressions in 142 cholangiocarcinoma and 20 benign bile duct tissue specimens using immunohistochemistry. Clinicopathologic characteristics and survival data were also collected and analyzed for their association with expression of these 3 proteins. \r\n\r\n Results: The data showed that both fascin and vimentin proteins were significantly overexpressed in cholangiocarcinoma, whereas E-cadherin expression was reduced in cholangiocarcinoma compared with normal tissues. Fascin protein expression was associated with tumor dedifferentiation, venous invasion and lymph node or distant metastasis. Similarly, vimentin expression was associated with tumor dedifferentiation and venous invasion, as well as hepatitis virus infection. In contrast, loss of E-cadherin expression was associated with tumor dedifferentiation (P < 0.05). Because the functions of these 3 proteins were closely related, the data showed that fascin and E-cadherin protein expression was reversely associated. However, fascin and vimentin protein expression was positively associated with cholangiocarcinoma. Cox multiple regression analysis showed that distant tumor metastasis, tumor differentiation and overexpression of fascin and vimentin proteins were all independent risk factors for prognosis (P < 0.05). \r\n\r\n Conclusion: The data from the current study demonstrated that overexpression of fascin and vimentin proteins could be further evaluated as biomarkers for the prediction of cholangiocarcinoma patient survival.","Source":"STN","category":"HUMAN","training_data":"Differential Expression Of Fascin E-Cadherin And Vimentin: Proteins Associated With Survival Of Cholangiocarcinoma Patients Introduction: This study investigated the differential expression of fascin, E-cadherin and vimentin in human carcinogenesis. \r\n\r\n Methods: This study detected their expressions in 142 cholangiocarcinoma and 20 benign bile duct tissue specimens using immunohistochemistry. Clinicopathologic characteristics and survival data were also collected and analyzed for their association with expression of these 3 proteins. \r\n\r\n Results: The data showed that both fascin and vimentin proteins were significantly overexpressed in cholangiocarcinoma, whereas E-cadherin expression was reduced in cholangiocarcinoma compared with normal tissues. Fascin protein expression was associated with tumor dedifferentiation, venous invasion and lymph node or distant metastasis. Similarly, vimentin expression was associated with tumor dedifferentiation and venous invasion, as well as hepatitis virus infection. In contrast, loss of E-cadherin expression was associated with tumor dedifferentiation (P < 0.05). Because the functions of these 3 proteins were closely related, the data showed that fascin and E-cadherin protein expression was reversely associated. However, fascin and vimentin protein expression was positively associated with cholangiocarcinoma. Cox multiple regression analysis showed that distant tumor metastasis, tumor differentiation and overexpression of fascin and vimentin proteins were all independent risk factors for prognosis (P < 0.05). \r\n\r\n Conclusion: The data from the current study demonstrated that overexpression of fascin and vimentin proteins could be further evaluated as biomarkers for the prediction of cholangiocarcinoma patient survival. STN","prediction_labels":"HUMAN"},{"cleaned":"polymorphisms natural killer cell receptor protein 2d nkg2d risk factor cholangiocarcinoma background aims understanding significant genetic risk factors cholangiocarcinoma cc remains limited polymorphisms natural killer cell receptor g2d nkg2d gene shown increase risk cc transformation patients primary sclerosing cholangitis psc present validation study nkg2d polymorphisms cc patients without psc methods seven common single nucleotide polymorphisms snps nkg2d gene genotyped 164 non psc related cc subjects 257 controls haploview two snps positively identified previous scandinavian study rs11053781 rs2617167 included results seven genotyped snps associated risk cc furthermore haplotype analysis revealed evidence suggest haplotype differs frequency cases controls p 0 1 conclusion common genetic variation nkg2d correlate significantly sporadic cc risk contrast previous positive findings scandinavian study psc patients failure reproduce association may reflect important difference pathogenesis sporadic cc psc related cc given genetic susceptibility likely multifaceted complex validation studies include sporadic psc related cc required stn","probabilities":0.9467213,"Title":"Polymorphisms In Natural Killer Cell Receptor Protein 2D (Nkg2D) As A Risk Factor For Cholangiocarcinoma","Abstract":"Background and aims: Understanding of the significant genetic risk factors for Cholangiocarcinoma (CC) remains limited. Polymorphisms in the natural killer cell receptor G2D (NKG2D) gene have been shown to increase risk of CC transformation in patients with Primary Sclerosing Cholangitis (PSC). We present a validation study of NKG2D polymorphisms in CC patients without PSC. \r\n\r\n Methods: Seven common Single Nucleotide Polymorphisms (SNPs) of the NKG2D gene were genotyped in 164 non-PSC related CC subjects and 257 controls with HaploView. The two SNPs that were positively identified in the previous Scandinavian study, rs11053781 and rs2617167, were included. \r\n\r\n Results: The seven genotyped SNPs were not associated with risk of CC. Furthermore, haplotype analysis revealed that there was no evidence to suggest that any haplotype differs in frequency between cases and controls (P > 0.1). \r\n\r\n Conclusion: The common genetic variation in NKG2D does not correlate significantly with sporadic CC risk. This is in contrast to the previous positive findings in the Scandinavian study with PSC-patients. The failure to reproduce the association may reflect an important difference between the pathogenesis of sporadic CC and that of PSC-related CC. Given that genetic susceptibility is likely to be multifaceted and complex, further validation studies that include both sporadic and PSC-related CC are required.","Source":"STN","category":"HUMAN","training_data":"Polymorphisms In Natural Killer Cell Receptor Protein 2D (Nkg2D) As A Risk Factor For Cholangiocarcinoma Background and aims: Understanding of the significant genetic risk factors for Cholangiocarcinoma (CC) remains limited. Polymorphisms in the natural killer cell receptor G2D (NKG2D) gene have been shown to increase risk of CC transformation in patients with Primary Sclerosing Cholangitis (PSC). We present a validation study of NKG2D polymorphisms in CC patients without PSC. \r\n\r\n Methods: Seven common Single Nucleotide Polymorphisms (SNPs) of the NKG2D gene were genotyped in 164 non-PSC related CC subjects and 257 controls with HaploView. The two SNPs that were positively identified in the previous Scandinavian study, rs11053781 and rs2617167, were included. \r\n\r\n Results: The seven genotyped SNPs were not associated with risk of CC. Furthermore, haplotype analysis revealed that there was no evidence to suggest that any haplotype differs in frequency between cases and controls (P > 0.1). \r\n\r\n Conclusion: The common genetic variation in NKG2D does not correlate significantly with sporadic CC risk. This is in contrast to the previous positive findings in the Scandinavian study with PSC-patients. The failure to reproduce the association may reflect an important difference between the pathogenesis of sporadic CC and that of PSC-related CC. Given that genetic susceptibility is likely to be multifaceted and complex, further validation studies that include both sporadic and PSC-related CC are required. STN","prediction_labels":"ANIMAL"},{"cleaned":"epigenetic aberrations cholangiocarcinoma potential biomarkers promising target novel therapeutic strategies cholangiocarcinoma cca notoriously lethal malignancy arising biliary tract epithelium relatively rare incidence rates increased markedly worldwide past decade although definite risk factors primary sclerosing cholangitis liver fluke infestation hepatolithiasis well documented cause cca remains unknown cases importance genetic alterations also epigenetic aberrations including promoter hypermethylation histone modifications indicated processes carcinogenesis pathogenesis cca review focuses epigenetic mechanisms involved cca genesis special emphasis applicability potential biomarkers diagnosis prognosis prediction well promising targets novel therapeutic strategies pubmed","probabilities":0.9799733,"Title":"Epigenetic aberrations in cholangiocarcinoma: potential biomarkers and promising target for novel therapeutic strategies","Abstract":"Cholangiocarcinoma (CCA) is a notoriously lethal malignancy arising from the biliary tract epithelium. While relatively rare, incidence rates have increased markedly worldwide in the past decade. Although definite risk factors such as primary sclerosing cholangitis, liver fluke infestation, and hepatolithiasis have been well- documented, the cause of CCA remains unknown for most cases. An importance of not only genetic alterations but also epigenetic aberrations, including promoter hypermethylation and histone modifications, has been indicated for the processes of carcinogenesis and pathogenesis of CCA. This review focuses on epigenetic mechanisms involved in CCA genesis, with special emphasis on their applicability as potential biomarkers for diagnosis, prognosis and prediction as well as promising targets for novel therapeutic strategies.","Source":"PubMed","category":"HUMAN","training_data":"Epigenetic aberrations in cholangiocarcinoma: potential biomarkers and promising target for novel therapeutic strategies Cholangiocarcinoma (CCA) is a notoriously lethal malignancy arising from the biliary tract epithelium. While relatively rare, incidence rates have increased markedly worldwide in the past decade. Although definite risk factors such as primary sclerosing cholangitis, liver fluke infestation, and hepatolithiasis have been well- documented, the cause of CCA remains unknown for most cases. An importance of not only genetic alterations but also epigenetic aberrations, including promoter hypermethylation and histone modifications, has been indicated for the processes of carcinogenesis and pathogenesis of CCA. This review focuses on epigenetic mechanisms involved in CCA genesis, with special emphasis on their applicability as potential biomarkers for diagnosis, prognosis and prediction as well as promising targets for novel therapeutic strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association green tea coffee consumption biliary tract cancer population based cohort study japan green tea coffee consumption may decrease risk types cancers however effects biliary tract cancer btc poorly understood population based prospective cohort study japan investigated association green tea total green tea sencha bancha genmaicha coffee consumption risk btc subtypes gallbladder cancer extrahepatic bile duct cancer hazard ratios 95 confidence intervals calculated using cox proportional hazard model total 89 555 people aged 45 74 years enrolled 1995 1999 followed 1 138 623 person years 2010 284 cases btc identified consumption 720 ml day green tea significantly associated decreased risk compared consumption 120 ml day hazard ratio 0 67 95 confidence interval 0 46 0 97 non significant trend decreased risk associated increased consumption observed p trend 0 095 analysis according location primary tumor consuming 120 ml green tea tended associated decreased risk gallbladder cancer extrahepatic bile duct cancer sencha bancha genmaicha analyzed separately observed non significant trend decreased risk btc associated sencha association bancha genmaicha coffee clear association biliary tract gallbladder extrahepatic bile duct cancer findings suggest high green tea consumption may lower risk btc effect may attributable sencha consumption pubmed","probabilities":0.9799733,"Title":"Association between green tea/coffee consumption and biliary tract cancer: A population-based cohort study in Japan","Abstract":"Green tea and coffee consumption may decrease the risk of some types of cancers. However, their effects on biliary tract cancer (BTC) have been poorly understood. In this population-based prospective cohort study in Japan, we investigated the association of green tea (total green tea, Sencha, and Bancha/Genmaicha) and coffee consumption with the risk for BTC and its subtypes, gallbladder cancer, and extrahepatic bile duct cancer. The hazard ratios and 95% confidence intervals were calculated using the Cox proportional hazard model. A total of 89 555 people aged 45-74 years were enrolled between 1995 and 1999 and followed up for 1 138 623 person-years until 2010, during which 284 cases of BTC were identified. Consumption of >720 mL/day green tea was significantly associated with decreased risk compared with consumption of ≤120 mL/day (hazard ratio = 0.67 [95% confidence interval, 0.46-0.97]), and a non-significant trend of decreased risk associated with increased consumption was observed (P-trend = 0.095). In the analysis according to the location of the primary tumor, consuming >120 mL green tea tended to be associated with decreased risk of gallbladder cancer and extrahepatic bile duct cancer. When Sencha and Bancha/Genmaicha were analyzed separately, we observed a non-significant trend of decreased risk of BTC associated with Sencha but no association with Bancha/Genmaicha. For coffee, there was no clear association with biliary tract, gallbladder, or extrahepatic bile duct cancer. Our findings suggest that high green tea consumption may lower the risk of BTC, and the effect may be attributable to Sencha consumption.","Source":"PubMed","category":"HUMAN","training_data":"Association between green tea/coffee consumption and biliary tract cancer: A population-based cohort study in Japan Green tea and coffee consumption may decrease the risk of some types of cancers. However, their effects on biliary tract cancer (BTC) have been poorly understood. In this population-based prospective cohort study in Japan, we investigated the association of green tea (total green tea, Sencha, and Bancha/Genmaicha) and coffee consumption with the risk for BTC and its subtypes, gallbladder cancer, and extrahepatic bile duct cancer. The hazard ratios and 95% confidence intervals were calculated using the Cox proportional hazard model. A total of 89 555 people aged 45-74 years were enrolled between 1995 and 1999 and followed up for 1 138 623 person-years until 2010, during which 284 cases of BTC were identified. Consumption of >720 mL/day green tea was significantly associated with decreased risk compared with consumption of ≤120 mL/day (hazard ratio = 0.67 [95% confidence interval, 0.46-0.97]), and a non-significant trend of decreased risk associated with increased consumption was observed (P-trend = 0.095). In the analysis according to the location of the primary tumor, consuming >120 mL green tea tended to be associated with decreased risk of gallbladder cancer and extrahepatic bile duct cancer. When Sencha and Bancha/Genmaicha were analyzed separately, we observed a non-significant trend of decreased risk of BTC associated with Sencha but no association with Bancha/Genmaicha. For coffee, there was no clear association with biliary tract, gallbladder, or extrahepatic bile duct cancer. Our findings suggest that high green tea consumption may lower the risk of BTC, and the effect may be attributable to Sencha consumption. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long noncoding rna gcaspc target mir 17 3p negatively regulates pyruvate carboxylase dependent cell proliferation gallbladder cancer long noncoding rnas lncrna implicated development many cancers report discovery critical role lncrna gcaspc determining progression gallbladder cancer differentially expressed lncrnas mrnas gallbladder cancer specimens paired adjacent nontumor tissues five patients identified validated expression microarray analysis quantitative real time pcr used measure gcaspc levels tissues 42 gallbladder cancer patients levels gcaspc confirmed separate cohort 89 gallbladder cancer patients gcaspc overexpressed silenced several gallbladder cancer cell lines molecular biological analyses performed gcaspc levels significantly lower gallbladder cancer adjacent nontumor tissues associated tumor size american joint committee cancer tumor stage patient outcomes gcaspc overexpression suppressed cell proliferation vitro vivo whereas gcaspc silencing opposite effects rna pull mass spectrometry identified pyruvate carboxylase rna binding protein associated gcaspc gcaspc target mir 17 3p confirmed mir 17 3p gcaspc downregulated pyruvate carboxylase level activity limiting protein stability taken together results defined novel mechanism lncrna regulated cell proliferation gallbladder cancer illuminating new basis understanding pathogenicity cancer res 76 18 5361 71 2016 aacr pubmed","probabilities":0.875,"Title":"Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase-Dependent Cell Proliferation in Gallbladder Cancer","Abstract":"Long noncoding RNAs (lncRNA) are being implicated in the development of many cancers. Here, we report the discovery of a critical role for the lncRNA GCASPC in determining the progression of gallbladder cancer. Differentially expressed lncRNAs and mRNAs between gallbladder cancer specimens and paired adjacent nontumor tissues from five patients were identified and validated by an expression microarray analysis. Quantitative real-time PCR was used to measure GCASPC levels in tissues from 42 gallbladder cancer patients, and levels of GCASPC were confirmed further in a separate cohort of 89 gallbladder cancer patients. GCASPC was overexpressed or silenced in several gallbladder cancer cell lines where molecular and biological analyses were performed. GCASPC levels were significantly lower in gallbladder cancer than adjacent nontumor tissues and were associated with tumor size, American Joint Committee on Cancer tumor stage, and patient outcomes. GCASPC overexpression suppressed cell proliferation in vitro and in vivo, whereas GCASPC silencing had opposite effects. By RNA pull-down and mass spectrometry, we identified pyruvate carboxylase as an RNA-binding protein that associated with GCASPC. Because GCASPC is a target of miR-17-3p, we confirmed that both miR-17-3p and GCASPC downregulated pyruvate carboxylase level and activity by limiting protein stability. Taken together, our results defined a novel mechanism of lncRNA-regulated cell proliferation in gallbladder cancer, illuminating a new basis for understanding its pathogenicity. Cancer Res; 76(18); 5361-71. ©2016 AACR.","Source":"PubMed","category":"ANIMAL","training_data":"Long Noncoding RNA GCASPC, a Target of miR-17-3p, Negatively Regulates Pyruvate Carboxylase-Dependent Cell Proliferation in Gallbladder Cancer Long noncoding RNAs (lncRNA) are being implicated in the development of many cancers. Here, we report the discovery of a critical role for the lncRNA GCASPC in determining the progression of gallbladder cancer. Differentially expressed lncRNAs and mRNAs between gallbladder cancer specimens and paired adjacent nontumor tissues from five patients were identified and validated by an expression microarray analysis. Quantitative real-time PCR was used to measure GCASPC levels in tissues from 42 gallbladder cancer patients, and levels of GCASPC were confirmed further in a separate cohort of 89 gallbladder cancer patients. GCASPC was overexpressed or silenced in several gallbladder cancer cell lines where molecular and biological analyses were performed. GCASPC levels were significantly lower in gallbladder cancer than adjacent nontumor tissues and were associated with tumor size, American Joint Committee on Cancer tumor stage, and patient outcomes. GCASPC overexpression suppressed cell proliferation in vitro and in vivo, whereas GCASPC silencing had opposite effects. By RNA pull-down and mass spectrometry, we identified pyruvate carboxylase as an RNA-binding protein that associated with GCASPC. Because GCASPC is a target of miR-17-3p, we confirmed that both miR-17-3p and GCASPC downregulated pyruvate carboxylase level and activity by limiting protein stability. Taken together, our results defined a novel mechanism of lncRNA-regulated cell proliferation in gallbladder cancer, illuminating a new basis for understanding its pathogenicity. Cancer Res; 76(18); 5361-71. ©2016 AACR. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"rationale initiating neoadjuvant chemotherapy hilar cholangiocarcinoma proposal criteria borderline resectable field surgery hilar cholangiocarcinoma background concept borderline resectable recently introduced field surgery pancreatic cancer surgical outcomes disease extremely dismal prognosis improved since introduction concept however concept yet introduced field surgery hilar cholangiocarcinoma hcca aim determine definition criteria borderline resectable field surgery hcca patients methods retrospective analysis 88 patients undergoing curative intent surgery hcca institution may 1992 december 2008 clarify independent prognostic factors results survival outcomes obtained 88 patients 5 year overall survival rate 31 8 independent factors predictive cancer death determined multivariate analysis presence regional lymph node metastasis lnm pathological confirmed vascular invasion vi cumulative survival rates 23 patients lnm vi underwent surgery significantly worse remaining 65 surgically treated patients similar 26 patients considered unresectable disease treated non surgical multidisciplinary treatment study period conclusion outcomes surgery cases hcca showing regional lnm vi better non surgical treatment unresectable disease coexistence two factors indicates oncologically dismal condition thus cases considered borderline resectable treatments additional surgery required borderline resectable cases obtain better outcomes pubmed","probabilities":0.9799733,"Title":"Our Rationale of Initiating Neoadjuvant Chemotherapy for Hilar Cholangiocarcinoma: A Proposal of Criteria for Borderline Resectable in the Field of Surgery for Hilar Cholangiocarcinoma","Abstract":"BACKGROUND: The concept of \"borderline resectable\" was recently introduced to the field of surgery for pancreatic cancer, and surgical outcomes for this disease with extremely dismal prognosis have improved since the introduction of this concept. However, no such concept has yet been introduced to the field of surgery for hilar cholangiocarcinoma (HCca). AIM: To determine a definition and criteria for \"borderline resectable\" in the field of surgery for HCca. PATIENTS AND METHODS: Retrospective analysis of 88 patients undergoing curative-intent surgery for HCca at our institution between May 1992 and December 2008 to clarify independent prognostic factors. RESULTS: Survival outcomes were obtained for these 88 patients, with a 5-year overall survival rate of 31.8%. Independent factors predictive of cancer death were determined by multivariate analysis to be the presence of regional lymph node metastasis (LNM) and pathological confirmed vascular invasion (VI). Cumulative survival rates of 23 patients with both LNM and VI who underwent surgery were significantly worse than those of the remaining 65 surgically treated patients and similar to those of 26 patients who were considered to have unresectable disease and treated with non-surgical multidisciplinary treatment during the same study period. CONCLUSION: Outcomes of surgery for cases of HCca showing regional LNM and VI were no better than those of non-surgical treatment for unresectable disease. Coexistence of these two factors indicates oncologically dismal condition and thus such cases should be considered \"borderline resectable.\" Treatments additional to surgery are required for \"borderline resectable\" cases to obtain better outcomes.","Source":"PubMed","category":"HUMAN","training_data":"Our Rationale of Initiating Neoadjuvant Chemotherapy for Hilar Cholangiocarcinoma: A Proposal of Criteria for Borderline Resectable in the Field of Surgery for Hilar Cholangiocarcinoma BACKGROUND: The concept of \"borderline resectable\" was recently introduced to the field of surgery for pancreatic cancer, and surgical outcomes for this disease with extremely dismal prognosis have improved since the introduction of this concept. However, no such concept has yet been introduced to the field of surgery for hilar cholangiocarcinoma (HCca). AIM: To determine a definition and criteria for \"borderline resectable\" in the field of surgery for HCca. PATIENTS AND METHODS: Retrospective analysis of 88 patients undergoing curative-intent surgery for HCca at our institution between May 1992 and December 2008 to clarify independent prognostic factors. RESULTS: Survival outcomes were obtained for these 88 patients, with a 5-year overall survival rate of 31.8%. Independent factors predictive of cancer death were determined by multivariate analysis to be the presence of regional lymph node metastasis (LNM) and pathological confirmed vascular invasion (VI). Cumulative survival rates of 23 patients with both LNM and VI who underwent surgery were significantly worse than those of the remaining 65 surgically treated patients and similar to those of 26 patients who were considered to have unresectable disease and treated with non-surgical multidisciplinary treatment during the same study period. CONCLUSION: Outcomes of surgery for cases of HCca showing regional LNM and VI were no better than those of non-surgical treatment for unresectable disease. Coexistence of these two factors indicates oncologically dismal condition and thus such cases should be considered \"borderline resectable.\" Treatments additional to surgery are required for \"borderline resectable\" cases to obtain better outcomes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"soluble programmed death ligand 1 spdl1 neutrophil lymphocyte ratio nlr predicts survival advanced biliary tract cancer patients treated palliative chemotherapy programmed death ligand 1 pd l1 expression tumor tissue investigation candidate biomarker immuno oncology dug development soluble form pd l1 spdl1 suggested immunosuppressive activity study measured serum level spdl1 evaluated prognostic implication biliary tract cancer btc blood collected 158 advanced btc patients 68 intrahepatic cholangiocarcinoma 56 gallbladder cancer 22 extrahepatic cholangiocarcinoma 12 ampulla vater cancer initiation palliative chemotherapy serum spdl1 measured using enzyme linked immunosorbent assay clinical data included neutrophil lymphocyte ratio nlr platelet lymphocyte ratio plr systemic immune inflammation index sii neutrophil platelet lymphocyte patients assigned two cohorts training validation cohort using simple random sampling method validate cut value marker validation performed using twofold cross validation method overall survival os patients 9 07 months 95 ci 8 20 11 33 median spdl1 1 20 ng ml range 0 03 7 28 mean 1 50 sd 1 22 median nlr plr sii 2 60 142 85 584 93 respectively patients high spdl1 0 94 ng ml showed worse os patients low spdl1 7 93 vs 14 10 months hr 1 891 1 35 2 65 p 0 001 multivariate analysis high spdl1 nlr independent poor prognostic factors conclusion serum spdl1 measured significant role prognosis advanced btc patients treated palliative chemotherapy pubmed","probabilities":0.7966102,"Title":"Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy","Abstract":"Programmed death-ligand 1 (PD-L1) expression in tumor tissue is under investigation as a candidate biomarker in immuno-oncology dug development. The soluble form of PD-L1 (sPDL1) is suggested to have immunosuppressive activity. In this study, we measured the serum level of sPDL1 and evaluated its prognostic implication in biliary tract cancer (BTC). Blood was collected from 158 advanced BTC patients (68 intrahepatic cholangiocarcinoma, 56 gallbladder cancer, 22 extrahepatic cholangiocarcinoma and 12 ampulla of vater cancer) before initiation of palliative chemotherapy. Serum sPDL1 was measured using an enzyme-linked immunosorbent assay. Clinical data included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII, neutrophil × platelet/lymphocyte). The patients were assigned to two cohorts (training and validation cohort) using a simple random sampling method to validate the cut-off value of each marker. Validation was performed using a twofold cross-validation method. Overall survival (OS) of all patients was 9.07 months (95% CI: 8.20-11.33). Median sPDL1 was 1.20 ng/mL (range 0.03-7.28, mean 1.50, SD 1.22). Median NLR, PLR and SII were 2.60, 142.85 and 584.93, respectively. Patients with high sPDL1 (≥0.94 ng/mL) showed worse OS than patients with low sPDL1 (7.93 vs. 14.10 months, HR 1.891 (1.35-2.65), p<0.001). In multivariate analysis, high sPDL1 and NLR were independent poor prognostic factors. In conclusion, serum sPDL1 can be measured and has significant role on the prognosis of advanced BTC patients treated with palliative chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Soluble programmed death-ligand 1 (sPDL1) and neutrophil-to-lymphocyte ratio (NLR) predicts survival in advanced biliary tract cancer patients treated with palliative chemotherapy Programmed death-ligand 1 (PD-L1) expression in tumor tissue is under investigation as a candidate biomarker in immuno-oncology dug development. The soluble form of PD-L1 (sPDL1) is suggested to have immunosuppressive activity. In this study, we measured the serum level of sPDL1 and evaluated its prognostic implication in biliary tract cancer (BTC). Blood was collected from 158 advanced BTC patients (68 intrahepatic cholangiocarcinoma, 56 gallbladder cancer, 22 extrahepatic cholangiocarcinoma and 12 ampulla of vater cancer) before initiation of palliative chemotherapy. Serum sPDL1 was measured using an enzyme-linked immunosorbent assay. Clinical data included neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and systemic immune-inflammation index (SII, neutrophil × platelet/lymphocyte). The patients were assigned to two cohorts (training and validation cohort) using a simple random sampling method to validate the cut-off value of each marker. Validation was performed using a twofold cross-validation method. Overall survival (OS) of all patients was 9.07 months (95% CI: 8.20-11.33). Median sPDL1 was 1.20 ng/mL (range 0.03-7.28, mean 1.50, SD 1.22). Median NLR, PLR and SII were 2.60, 142.85 and 584.93, respectively. Patients with high sPDL1 (≥0.94 ng/mL) showed worse OS than patients with low sPDL1 (7.93 vs. 14.10 months, HR 1.891 (1.35-2.65), p<0.001). In multivariate analysis, high sPDL1 and NLR were independent poor prognostic factors. In conclusion, serum sPDL1 can be measured and has significant role on the prognosis of advanced BTC patients treated with palliative chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ruthenium complex induce cell death g 415 gallbladder cancer cells purpose work present recently developed ruthenium complex shows anticancer activity gallbladder cancer cells methods synthesis new ruthenium complexes antiproliferative cytotoxicity apoptosis activities evaluated vitro triple assay apotox glo transcription levels genes related apoptosis evaluated real time pcr q pcr results ruthenium complex called ru ucn3 inhibits proliferation gallbladder cancer cells g 415 means apoptosis demonstrated overexpression pro apoptotic genes puma diablo caspasa 9 together repression anti apoptotic genes bcl xl bcl 2 addition found strong caspase 3 7 activity cells 24 h ru ucn3 exposure evaluated triple apotox glo assay conclusion new ruthenium complexes evaluated inhibitory effect g 415 cells think ru ucn3 promising anticancer agent explored vitro vivo assays probably chemical modulation molecule stn","probabilities":0.9467213,"Title":"Ruthenium Complex Induce Cell Death In G-415 Gallbladder Cancer Cells","Abstract":"Purpose: In this work, we present a recently developed ruthenium complex that shows anticancer activity in gallbladder cancer cells. \r\n\r\n Methods: After the synthesis of the new ruthenium complexes, the antiproliferative, cytotoxicity, and apoptosis activities were evaluated in vitro by the triple assay ApoTox-Glo. Then, the transcription levels of genes related to apoptosis were evaluated by real-time PCR (q-PCR). \r\n\r\n Results: The ruthenium complex, called Ru-UCN3, inhibits the proliferation of gallbladder cancer cells G-415 by means of apoptosis, which was demonstrated by the overexpression of the pro-apoptotic genes Puma, Diablo, and Caspasa-9 together with the repression of the anti-apoptotic genes Bcl-xL and Bcl-2. In addition, we found strong caspase 3/7 activity in the cells at 24 h of the Ru-UCN3 exposure, which was evaluated by the triple ApoTox-Glo assay. \r\n\r\n Conclusion: The new ruthenium complexes evaluated had an inhibitory effect on G-415 cells. We think that Ru-UCN3 could be a promising anticancer agent, which should be explored with more in vitro and in vivo assays and probably with the chemical modulation of this molecule.","Source":"STN","category":"ANIMAL","training_data":"Ruthenium Complex Induce Cell Death In G-415 Gallbladder Cancer Cells Purpose: In this work, we present a recently developed ruthenium complex that shows anticancer activity in gallbladder cancer cells. \r\n\r\n Methods: After the synthesis of the new ruthenium complexes, the antiproliferative, cytotoxicity, and apoptosis activities were evaluated in vitro by the triple assay ApoTox-Glo. Then, the transcription levels of genes related to apoptosis were evaluated by real-time PCR (q-PCR). \r\n\r\n Results: The ruthenium complex, called Ru-UCN3, inhibits the proliferation of gallbladder cancer cells G-415 by means of apoptosis, which was demonstrated by the overexpression of the pro-apoptotic genes Puma, Diablo, and Caspasa-9 together with the repression of the anti-apoptotic genes Bcl-xL and Bcl-2. In addition, we found strong caspase 3/7 activity in the cells at 24 h of the Ru-UCN3 exposure, which was evaluated by the triple ApoTox-Glo assay. \r\n\r\n Conclusion: The new ruthenium complexes evaluated had an inhibitory effect on G-415 cells. We think that Ru-UCN3 could be a promising anticancer agent, which should be explored with more in vitro and in vivo assays and probably with the chemical modulation of this molecule. STN","prediction_labels":"ANIMAL"},{"cleaned":"tumor lysate loaded dendritic cells induce cell specific antitumor response gallbladder cancer introduction although infrequent gallbladder cancer gbc high incidence rates south america fact chile highest gbc incidence mortality worldwide currently surgery effective treatment five year survival rate less 10 previously demonstrated allogeneic melanoma cell lysates loaded dendritic cells dcs provide standardized applicable tumor specific vaccine capable induce cell mediated immune response melanoma patients improving survival investigated effect tumor lysates derived gallbladder cancer cell gcc lines immature dcs capacity induce cell mediated anti gbc responses vitro material methods dcs stimulated gcc lysates analyzed flow cytometry panel surface markers autologous cd3 cells co cultured dcs 14 days cd4 cd8 cells analyzed flow cytometry activation chemokine receptor expression cd8 cells isolated co cultured gcc lines gbd1 tgbc 2tkb melanoma cell line mel1 16hrs ifn secretion measured elispot results gcc lysates induced dcs maturation increasing surface expression mhc mhc ii cd80 cd83 cd86 ccr7 dcs maturated gcc lysate induced cd3 cells activation increasing expression cd25 cd69 cxcr3 cxcr4 cd4 cd8 cells compared non stimulated lymphocytes additionally cd8 cells co cultured gbc loaded dcs released higher amounts ifn controls discussion based results dcs maturated gcc lysates capable induce specific cells activation gbc considered future immunotherapy approaches google scholar","probabilities":0.9467213,"Title":"Tumor Lysate Loaded Dendritic Cells Induce A T Cell Specific Antitumor Response Against Gallbladder Cancer","Abstract":"Introduction Although infrequent, Gallbladder cancer (GBC) has high incidence rates in South America. In fact, Chile has the highest GBC incidence and mortality worldwide. Currently, surgery is the only effective treatment, and the five-year survival rate is less than 10%. Previously, we demonstrated that allogeneic melanoma cell lysates-loaded dendritic cells (DCs) provide a standardized, applicable tumor-specific vaccine; capable to induce a cell mediated immune response in melanoma patients, improving survival. Here, we investigated the effect of tumor lysates derived from gallbladder cancer cell (GCC) lines on immature DCs and their capacity to induce a T cell mediated anti GBC responses in vitro.\nMaterial and Methods DCs were stimulated with GCC lysates and analyzed by flow cytometry for a panel of surface markers. Autologous CD3+ T cells were co-cultured with these DCs for 14 days. CD4+ and CD8+ T cells were analyzed by flow cytometry for activation and chemokine receptor expression. CD8+ T cells were isolated and co-cultured with GCC lines GBd1, TGBC-2TKB and melanoma cell line Mel1 for 16hrs. IFN-γ secretion was measured by ELISPOT.\nResults All GCC lysates induced DCs maturation, increasing surface expression of MHC-I, MHC-II, CD80, CD83, CD86, CCR7. DCs maturated with GCC lysate induced CD3+ T cells activation, increasing expression of CD25, CD69, CXCR3, CXCR4 in both CD4+ and CD8+ T cells compared with non-stimulated lymphocytes. Additionally, CD8+ T cells co-cultured with GBC-loaded DCs, released higher amounts of IFN-γ than controls.\nDiscussion Based on these results, DCs maturated with GCC lysates are capable to induce specific T cells activation against GBC and can be considered for future immunotherapy approaches.","Source":"Google Scholar","category":"ANIMAL","training_data":"Tumor Lysate Loaded Dendritic Cells Induce A T Cell Specific Antitumor Response Against Gallbladder Cancer Introduction Although infrequent, Gallbladder cancer (GBC) has high incidence rates in South America. In fact, Chile has the highest GBC incidence and mortality worldwide. Currently, surgery is the only effective treatment, and the five-year survival rate is less than 10%. Previously, we demonstrated that allogeneic melanoma cell lysates-loaded dendritic cells (DCs) provide a standardized, applicable tumor-specific vaccine; capable to induce a cell mediated immune response in melanoma patients, improving survival. Here, we investigated the effect of tumor lysates derived from gallbladder cancer cell (GCC) lines on immature DCs and their capacity to induce a T cell mediated anti GBC responses in vitro.\nMaterial and Methods DCs were stimulated with GCC lysates and analyzed by flow cytometry for a panel of surface markers. Autologous CD3+ T cells were co-cultured with these DCs for 14 days. CD4+ and CD8+ T cells were analyzed by flow cytometry for activation and chemokine receptor expression. CD8+ T cells were isolated and co-cultured with GCC lines GBd1, TGBC-2TKB and melanoma cell line Mel1 for 16hrs. IFN-γ secretion was measured by ELISPOT.\nResults All GCC lysates induced DCs maturation, increasing surface expression of MHC-I, MHC-II, CD80, CD83, CD86, CCR7. DCs maturated with GCC lysate induced CD3+ T cells activation, increasing expression of CD25, CD69, CXCR3, CXCR4 in both CD4+ and CD8+ T cells compared with non-stimulated lymphocytes. Additionally, CD8+ T cells co-cultured with GBC-loaded DCs, released higher amounts of IFN-γ than controls.\nDiscussion Based on these results, DCs maturated with GCC lysates are capable to induce specific T cells activation against GBC and can be considered for future immunotherapy approaches. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"comparison sixth seventh editions ajcc tnm classification gallbladder cancer background study aimed compare seventh edition tumor node metastasis tnm staging system sixth edition validate usefulness predicting prognosis gallbladder cancer methods gallbladder cancer patients staged according sixth seventh editions american joint committee cancer ajcc staging system results total 142 patients underwent cholecystectomy gallbladder cancer according seventh edition survival time n1 n2 different p 0 006 survival difference n0 n1 became significant excluding cases lymph node dissection p 0 035 2 log likelihoods sixth seventh edition tnm stages 216 282 217 460 respectively suggesting non superiority seventh edition excluding cases lymph node dissection resulted lower 2 log likelihood score editions sixth 157 002 seventh 158 758 conclusions sufficient lymph node dissection allows better prognostic stratification application ajcc staging system even though new n stage seventh edition showed improvement predicting prognosis overall performance seventh edition much better sixth improvement needed gallbladder cancer staging system pubmed","probabilities":0.9799733,"Title":"Comparison of the sixth and seventh editions of the AJCC TNM classification for gallbladder cancer","Abstract":"BACKGROUND: This study aimed to compare the seventh edition of the tumor node metastasis (TNM) staging system to the sixth edition to validate its usefulness in predicting prognosis for gallbladder cancer. METHODS: Gallbladder cancer patients were staged according to both the sixth and seventh editions of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: A total of 142 patients underwent cholecystectomy for gallbladder cancer. According to the seventh edition, the survival time of N1 and N2 was different (P = 0.006), and the survival difference between N0 and N1 became significant after excluding cases with no lymph node dissection (P = 0.035). The -2 log likelihoods of the sixth and seventh edition TNM stages were 216.282 and 217.460, respectively, suggesting non-superiority of the seventh edition. Excluding cases with no lymph node dissection resulted in a lower -2 log likelihood score for both editions (sixth, 157.002; seventh, 158.758). CONCLUSIONS: Sufficient lymph node dissection allows better prognostic stratification by application of the AJCC staging system. Even though the new N stage of the seventh edition showed some improvement in predicting prognosis, the overall performance of the seventh edition was not much better than the sixth. Further improvement is needed in the gallbladder cancer staging system.","Source":"PubMed","category":"HUMAN","training_data":"Comparison of the sixth and seventh editions of the AJCC TNM classification for gallbladder cancer BACKGROUND: This study aimed to compare the seventh edition of the tumor node metastasis (TNM) staging system to the sixth edition to validate its usefulness in predicting prognosis for gallbladder cancer. METHODS: Gallbladder cancer patients were staged according to both the sixth and seventh editions of the American Joint Committee on Cancer (AJCC) staging system. RESULTS: A total of 142 patients underwent cholecystectomy for gallbladder cancer. According to the seventh edition, the survival time of N1 and N2 was different (P = 0.006), and the survival difference between N0 and N1 became significant after excluding cases with no lymph node dissection (P = 0.035). The -2 log likelihoods of the sixth and seventh edition TNM stages were 216.282 and 217.460, respectively, suggesting non-superiority of the seventh edition. Excluding cases with no lymph node dissection resulted in a lower -2 log likelihood score for both editions (sixth, 157.002; seventh, 158.758). CONCLUSIONS: Sufficient lymph node dissection allows better prognostic stratification by application of the AJCC staging system. Even though the new N stage of the seventh edition showed some improvement in predicting prognosis, the overall performance of the seventh edition was not much better than the sixth. Further improvement is needed in the gallbladder cancer staging system. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance nqo1 expression intrahepatic cholangiocarcinoma study aimed evaluate association immunohistochemical expression nad p h quinone oxidoreductase 1 nqo1 nuclear factor erythroid 2 related factor 2 nrf2 resected specimens intrahepatic cholangiocarcinoma icc elucidate prognostic value nqo1 nrf2 expression retrospective analysis conducted 34 consecutive patients underwent surgical resection icc immunohistochemistry resected specimens conducted using following primary monoclonal antibodies nqo1 nrf2 34 patients 23 classified tumors nqo1 positive expression 11 tumors loss nqo1 expression whereas 22 patients tumors nrf2 positive expression 12 tumors loss nrf2 expression nqo1 expression showed positive association nrf2 expression p 0 005 loss nqo1 expression frequent tumor specimens moderately poorly differentiated 11 26 42 well differentiated tumors 0 8 0 p 0 034 post resection survival significantly worse patients tumors loss nqo1 expression patients nqo1 positive tumors cumulative 5 year survival rate 0 51 respectively p 0 005 nrf2 expression associated survival resection p 0 287 cox proportional hazards regression analysis revealed lymph node involvement p 0 001 loss nqo1 expression p 0 001 independent adverse effect survival loss nqo1 expression reflects dedifferentiation thus indicates poor prognosis patients undergoing resection icc pubmed","probabilities":0.9799733,"Title":"Prognostic significance of NQO1 expression in intrahepatic cholangiocarcinoma","Abstract":"This study aimed to evaluate the association between the immunohistochemical expression of NAD(P) H:quinone oxidoreductase-1 (NQO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in resected specimens of intrahepatic cholangiocarcinoma (ICC) and to elucidate the prognostic value of NQO1 and Nrf2 expression. A retrospective analysis was conducted of 34 consecutive patients who underwent surgical resection for ICC. Immunohistochemistry of the resected specimens was conducted using each of the following primary monoclonal antibodies against NQO1 and Nrf2. Of the 34 patients, 23 were classified as having tumors with NQO1-positive expression and 11 had tumors with loss of NQO1 expression, whereas 22 patients had tumors with Nrf2-positive expression and 12 had tumors with loss of Nrf2 expression. NQO1 expression showed a positive association with Nrf2 expression (p=0.005). Loss of NQO1 expression was more frequent in tumor specimens that were moderately or poorly differentiated (11/26; 42%) than in well-differentiated tumors (0/8; 0%; p=0.034). Post-resection survival was significantly worse in patients with tumors with loss of NQO1 expression than in patients with NQO1-positive tumors (cumulative 5 -year survival rate of 0% and 51%, respectively; p=0.005). Nrf2 expression was not associated with survival after resection (p=0.287). The Cox proportional hazards regression analysis revealed that lymph node involvement (p<0.001) and loss of NQO1 expression (p<0.001) had an independent adverse effect on survival. Loss of NQO1 expression reflects dedifferentiation and thus indicates a poor prognosis for patients undergoing resection for ICC.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of NQO1 expression in intrahepatic cholangiocarcinoma This study aimed to evaluate the association between the immunohistochemical expression of NAD(P) H:quinone oxidoreductase-1 (NQO1) and nuclear factor erythroid 2-related factor 2 (Nrf2) in resected specimens of intrahepatic cholangiocarcinoma (ICC) and to elucidate the prognostic value of NQO1 and Nrf2 expression. A retrospective analysis was conducted of 34 consecutive patients who underwent surgical resection for ICC. Immunohistochemistry of the resected specimens was conducted using each of the following primary monoclonal antibodies against NQO1 and Nrf2. Of the 34 patients, 23 were classified as having tumors with NQO1-positive expression and 11 had tumors with loss of NQO1 expression, whereas 22 patients had tumors with Nrf2-positive expression and 12 had tumors with loss of Nrf2 expression. NQO1 expression showed a positive association with Nrf2 expression (p=0.005). Loss of NQO1 expression was more frequent in tumor specimens that were moderately or poorly differentiated (11/26; 42%) than in well-differentiated tumors (0/8; 0%; p=0.034). Post-resection survival was significantly worse in patients with tumors with loss of NQO1 expression than in patients with NQO1-positive tumors (cumulative 5 -year survival rate of 0% and 51%, respectively; p=0.005). Nrf2 expression was not associated with survival after resection (p=0.287). The Cox proportional hazards regression analysis revealed that lymph node involvement (p<0.001) and loss of NQO1 expression (p<0.001) had an independent adverse effect on survival. Loss of NQO1 expression reflects dedifferentiation and thus indicates a poor prognosis for patients undergoing resection for ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"type 2 diabetes mellitus risk gallbladder cancer systematic review meta analysis observational studies aims increasing evidence suggests history type 2 diabetes mellitus type 2 dm may involved development various sites cancer however association risk gallbladder cancer remains unclear methods identified studies literature search medline embase 31 august 2014 searching reference lists pertinent articles data independently extracted two investigators using standardized data abstraction tool summary relative risks srrs 95 confidence intervals cis calculated random effects model results total 20 studies eight case control studies 12 cohort studies included meta analysis analysis 20 studies found compared non diabetic individuals diabetic individuals increased risk gallbladder cancer srr 1 56 95 ci 1 36 1 79 evidence moderate heterogeneity among studies p 0 010 2 43 5 increased risk relationship independent smoking body mass index history gallstones however whether controlled alcohol use may one potential confounders significantly affect association type 2 dm risk gallbladder cancer diabetic women men similarly increased risk gallbladder cancer associated type 2 dm conclusions findings systematic review indicate compared non diabetic individuals men women type 2 dm increased risk gallbladder cancer copyright 2015 john wiley sons ltd pubmed","probabilities":0.9799733,"Title":"Type 2 diabetes mellitus and risk of gallbladder cancer: a systematic review and meta-analysis of observational studies","Abstract":"AIMS: Increasing evidence suggests that a history of type 2 diabetes mellitus (type 2 DM) may be involved in the development of various sites of cancer. However, the association with risk of gallbladder cancer remains unclear. METHODS: We identified studies by a literature search of MEDLINE and EMBASE through 31 August 2014 and by searching the reference lists of pertinent articles. All data were independently extracted by two investigators using a standardized data abstraction tool. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were calculated with a random effects model. RESULTS: A total of 20 studies (eight case-control studies and 12 cohort studies) were included in this meta-analysis. Analysis of these 20 studies found that compared with non-diabetic individuals, diabetic individuals had an increased risk of gallbladder cancer (SRR = 1.56, 95% CI: 1.36-1.79). There was evidence of moderate heterogeneity among these studies (p = 0.010 and I(2)  = 43.5%). This increased risk relationship is independent of smoking, body mass index and a history of gallstones. However, whether or not controlled for, alcohol use may be one of the potential confounders that significantly affect the association between type 2 DM and the risk of gallbladder cancer. Diabetic women and men had a similarly increased risk of gallbladder cancer associated with type 2 DM. CONCLUSIONS: These findings of this systematic review indicate that compared with non-diabetic individuals, both men and women with type 2 DM had an increased risk of gallbladder cancer. Copyright © 2015 John Wiley & Sons, Ltd.","Source":"PubMed","category":"HUMAN","training_data":"Type 2 diabetes mellitus and risk of gallbladder cancer: a systematic review and meta-analysis of observational studies AIMS: Increasing evidence suggests that a history of type 2 diabetes mellitus (type 2 DM) may be involved in the development of various sites of cancer. However, the association with risk of gallbladder cancer remains unclear. METHODS: We identified studies by a literature search of MEDLINE and EMBASE through 31 August 2014 and by searching the reference lists of pertinent articles. All data were independently extracted by two investigators using a standardized data abstraction tool. Summary relative risks (SRRs) with 95% confidence intervals (CIs) were calculated with a random effects model. RESULTS: A total of 20 studies (eight case-control studies and 12 cohort studies) were included in this meta-analysis. Analysis of these 20 studies found that compared with non-diabetic individuals, diabetic individuals had an increased risk of gallbladder cancer (SRR = 1.56, 95% CI: 1.36-1.79). There was evidence of moderate heterogeneity among these studies (p = 0.010 and I(2)  = 43.5%). This increased risk relationship is independent of smoking, body mass index and a history of gallstones. However, whether or not controlled for, alcohol use may be one of the potential confounders that significantly affect the association between type 2 DM and the risk of gallbladder cancer. Diabetic women and men had a similarly increased risk of gallbladder cancer associated with type 2 DM. CONCLUSIONS: These findings of this systematic review indicate that compared with non-diabetic individuals, both men and women with type 2 DM had an increased risk of gallbladder cancer. Copyright © 2015 John Wiley & Sons, Ltd. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical outcomes intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc considered fatal disease frequent recurrence despite curative surgery macroscopic classification icc general rules clinical pathological study primary liver cancer liver cancer study group japan reflects tumor spreading patterns therefore clinicopathological findings surgical outcomes predicted using classification lymph node intrahepatic metastases curative resection important prognostic factors icc however lymph node dissection still controversial particular intraductal growth type periductal infiltrating type icc without hilar invasion favorable surgical outcomes whereas mass forming type periductal infiltrating type icc hilar invasion high hepatic recurrence local recurrence respectively multimodal treatments therefore needed improve surgical outcomes icc pubmed","probabilities":0.9799733,"Title":"Surgical outcomes of intrahepatic cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is considered to be a fatal disease because of frequent recurrence despite curative surgery. The macroscopic classification of ICC in the General Rules for the Clinical and Pathological Study of Primary Liver Cancer of the Liver Cancer Study Group of Japan reflects tumor-spreading patterns; therefore, the clinicopathological findings and surgical outcomes can be predicted using this classification. Lymph node and intrahepatic metastases, and a curative resection are important prognostic factors in ICC; however, lymph node dissection is still controversial. In particular, the intraductal growth type and periductal infiltrating type of ICC without hilar invasion have favorable surgical outcomes, whereas the mass-forming type and periductal infiltrating type of ICC with hilar invasion have high hepatic recurrence and local recurrence, respectively. Multimodal treatments are therefore needed to improve the surgical outcomes of ICC.","Source":"PubMed","category":"HUMAN","training_data":"Surgical outcomes of intrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is considered to be a fatal disease because of frequent recurrence despite curative surgery. The macroscopic classification of ICC in the General Rules for the Clinical and Pathological Study of Primary Liver Cancer of the Liver Cancer Study Group of Japan reflects tumor-spreading patterns; therefore, the clinicopathological findings and surgical outcomes can be predicted using this classification. Lymph node and intrahepatic metastases, and a curative resection are important prognostic factors in ICC; however, lymph node dissection is still controversial. In particular, the intraductal growth type and periductal infiltrating type of ICC without hilar invasion have favorable surgical outcomes, whereas the mass-forming type and periductal infiltrating type of ICC with hilar invasion have high hepatic recurrence and local recurrence, respectively. Multimodal treatments are therefore needed to improve the surgical outcomes of ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effective enrichment cholangiocarcinoma secretomes using hollow fiber bioreactor culture system northeastern region thailand well known high incidence bile duct cancer known cholangiocarcinoma continued need improve diagnosis treatment discovery biomarkers early detection bile duct cancer greatly improve treatment outcome patients secretome collection proteins secreted cells useful source identifying circulating biomarkers blood secreted cancer cells hollow fiber bioreactor culture system used enrichment cholangiocarcinoma secretomes since culture system mimics dense three dimensional microenvironment tumor found vivo two dimensional fluorescence difference gel electrophoresis using sensitive fluor saturation dye staining followed lc ms ms used compare protein expression secretomes cells cultured hollow fiber system cells cultured monolayer culture system first time 2d patterns cholangiocarcinoma secretomes two culture systems compared hollow fiber system improved quality quantity cholangiocarcinoma secreted proteins compared conventional monolayer system showing less interference cytoplasmic proteins yielding secreted proteins overall 75 spots analyzed lc ms ms 106 secreted proteins identified two novel secreted proteins c19orf10 cystatin b found hollow fiber system absent traditional monolayer culture system among highly expressed proteins 22 secreted soluble proteins enriched 5 fold hollow fiber system compared monolayer culture system hollow fiber system therefore useful preparing wide range proteins low abundance cell secretomes stn","probabilities":0.9467213,"Title":"Effective Enrichment Of Cholangiocarcinoma Secretomes Using The Hollow Fiber Bioreactor Culture System","Abstract":"The Northeastern region of Thailand is well known to have high incidence of bile duct cancer known as cholangiocarcinoma. So there is a continued need to improve diagnosis and treatment, and discovery of biomarkers for early detection of bile duct cancer should greatly improve treatment outcome for these patients. The secretome, a collection of proteins secreted from cells, is a useful source for identifying circulating biomarkers in blood secreted from cancer cells. Here a Hollow Fiber Bioreactor culture system was used for enrichment of cholangiocarcinoma secretomes, since this culture system mimics the dense three-dimensional microenvironment of the tumor found in vivo. Two-dimensional fluorescence difference gel electrophoresis using a sensitive Fluor saturation dye staining, followed by LC/MS/MS, was used to compare protein expression in the secretomes of cells cultured in the Hollow Fiber system and cells cultured in the monolayer culture system. For the first time, the 2D-patterns of cholangiocarcinoma secretomes from the two culture systems could be compared. The Hollow Fiber system improved the quality and quantity of cholangiocarcinoma secreted proteins compared to conventional monolayer system, showing less interference by cytoplasmic proteins and yielding more secreted proteins. Overall, 75 spots were analyzed by LC/MS/MS and 106 secreted proteins were identified. Two novel secreted proteins (C19orf10 and cystatin B) were found only in the Hollow Fiber system and were absent from the traditional monolayer culture system. Among the highly expressed proteins, 22 secreted soluble proteins were enriched by 5 fold in Hollow Fiber system compared to monolayer culture system. The Hollow Fiber system is therefore useful for preparing a wide range of proteins from low-abundance cell secretomes.","Source":"STN","category":"ANIMAL","training_data":"Effective Enrichment Of Cholangiocarcinoma Secretomes Using The Hollow Fiber Bioreactor Culture System The Northeastern region of Thailand is well known to have high incidence of bile duct cancer known as cholangiocarcinoma. So there is a continued need to improve diagnosis and treatment, and discovery of biomarkers for early detection of bile duct cancer should greatly improve treatment outcome for these patients. The secretome, a collection of proteins secreted from cells, is a useful source for identifying circulating biomarkers in blood secreted from cancer cells. Here a Hollow Fiber Bioreactor culture system was used for enrichment of cholangiocarcinoma secretomes, since this culture system mimics the dense three-dimensional microenvironment of the tumor found in vivo. Two-dimensional fluorescence difference gel electrophoresis using a sensitive Fluor saturation dye staining, followed by LC/MS/MS, was used to compare protein expression in the secretomes of cells cultured in the Hollow Fiber system and cells cultured in the monolayer culture system. For the first time, the 2D-patterns of cholangiocarcinoma secretomes from the two culture systems could be compared. The Hollow Fiber system improved the quality and quantity of cholangiocarcinoma secreted proteins compared to conventional monolayer system, showing less interference by cytoplasmic proteins and yielding more secreted proteins. Overall, 75 spots were analyzed by LC/MS/MS and 106 secreted proteins were identified. Two novel secreted proteins (C19orf10 and cystatin B) were found only in the Hollow Fiber system and were absent from the traditional monolayer culture system. Among the highly expressed proteins, 22 secreted soluble proteins were enriched by 5 fold in Hollow Fiber system compared to monolayer culture system. The Hollow Fiber system is therefore useful for preparing a wide range of proteins from low-abundance cell secretomes. STN","prediction_labels":"ANIMAL"},{"cleaned":"association obesity gallbladder cancer obesity become global health issue increased morbidity mortality close association least 20 different cancers clinical epidemiological studies suggested obesity overweight positively related risk gbc gallbladder cancer gbc relatively infrequent highly lethal neoplasm obesity may disturb lipid endogenous hormones metabolism affect gallbladder motility increase risk gallstones thus plays role gbc control obesity measures lifestyle modification healthy diet regular exercise may prove useful prevention gbc pubmed","probabilities":0.9799733,"Title":"Association between obesity and gallbladder cancer","Abstract":"Obesity has become a global health issue because of its increased morbidity and mortality, and a close association with at least 20 different cancers. Clinical and epidemiological studies have suggested that obesity and overweight are positively related with the risk of GBC. Gallbladder cancer (GBC) is a relatively infrequent but highly lethal neoplasm. Obesity may disturb lipid and endogenous hormones metabolism, affect gallbladder motility, increase the risk of gallstones, and thus plays a role in GBC. Control of obesity through measures such as lifestyle modification, healthy diet, and regular exercise may prove useful in the prevention of GBC.","Source":"PubMed","category":"HUMAN","training_data":"Association between obesity and gallbladder cancer Obesity has become a global health issue because of its increased morbidity and mortality, and a close association with at least 20 different cancers. Clinical and epidemiological studies have suggested that obesity and overweight are positively related with the risk of GBC. Gallbladder cancer (GBC) is a relatively infrequent but highly lethal neoplasm. Obesity may disturb lipid and endogenous hormones metabolism, affect gallbladder motility, increase the risk of gallstones, and thus plays a role in GBC. Control of obesity through measures such as lifestyle modification, healthy diet, and regular exercise may prove useful in the prevention of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"evaluation clinical value concomitant portal vein resection advanced gallbladder carcinoma introduction recently reported clinical value surgical resection advanced gallbladder carcinoma involving extrahepatic bile duct locally advanced gallbladder carcinoma required concomitant portal vein resection pvr aggressively performed surgical resection aim study evaluate clinical value pvr advanced gallbladder carcinoma methods 2000 2010 127 consecutive patients gallbladder carcinoma underwent surgical resection 30 24 underwent pvr obtain complete resection two patients synchronous biliary malignant disease excluded study remaining 28 patients formed cohort present study medical records retrospectively reviewed results pancreatoduodenectomy pd gallbladder bed resection gb plus extrahepatic bile duct resection ebd gb plus pd major hepatectomy mh plus ebd mh plus pd hpd performed 1 1 4 14 8 patients respectively histologically 19 patients regional lymph node metastasis n 4 periaortic lymph node metastasis pa n 3 distant metastasis pa n m r0 resection achieved 20 71 patients five patients died postoperative complications 3 5 patients underwent hpd 5 year survival 23 patients tolerated surgery 33 actually 3 patients survived 5 years 5 year survivors patients underwent hpd conclusion long term survivors patients locally advanced gallbladder carcinoma underwent combined pvr surgical indication hpd pvr carefully considered google scholar","probabilities":0.9799733,"Title":"Evaluation Of Clinical Value Of Concomitant Portal Vein Resection For Advanced Gallbladder Carcinoma","Abstract":"Introduction: Recently, we reported clinical value of surgical resection for advanced gallbladder carcinoma involving the extrahepatic bile duct. For locally advanced gallbladder carcinoma which required concomitant portal vein resection (PVR), we have aggressively performed surgical resection.\nThe aim of this study is to evaluate clinical value of PVR for advanced gallbladder carcinoma. Methods: From 2000 to 2010, 127 consecutive patients with gallbladder carcinoma underwent surgical resection. Of them, 30 (24%) underwent PVR to obtain complete resection. Two patients who had synchronous biliary malignant disease were excluded from this study. The remaining 28 patients formed the cohort of the present study. Their medical records were retrospectively reviewed. Results: Pancreatoduodenectomy (PD), gallbladder bed resection (GB) plus extrahepatic bile duct resection (EBD), GB plus PD, major hepatectomy (MH) plus EBD, and MH plus PD (HPD) were performed in 1, 1, 4, 14, and 8 patients, respectively. Histologically, 19 patients had regional lymph node metastasis (N), 4 had periaortic lymph node metastasis (PA-N), and 3 had distant metastasis other than PA-N (M). R0 resection was achieved in 20 (71%) patients. Five patients died of postoperative complications, and 3 of the 5 patients underwent HPD. The 5-year survival for the 23 patients who tolerated surgery was 33%; actually, 3 patients survived more than 5 years. There were no 5-year survivors in the patients who underwent HPD. Conclusion: There were only a few long-term survivors in patients with locally advanced gallbladder carcinoma who underwent combined PVR. Surgical indication of HPD with PVR should be carefully considered","Source":"Google Scholar","category":"HUMAN","training_data":"Evaluation Of Clinical Value Of Concomitant Portal Vein Resection For Advanced Gallbladder Carcinoma Introduction: Recently, we reported clinical value of surgical resection for advanced gallbladder carcinoma involving the extrahepatic bile duct. For locally advanced gallbladder carcinoma which required concomitant portal vein resection (PVR), we have aggressively performed surgical resection.\nThe aim of this study is to evaluate clinical value of PVR for advanced gallbladder carcinoma. Methods: From 2000 to 2010, 127 consecutive patients with gallbladder carcinoma underwent surgical resection. Of them, 30 (24%) underwent PVR to obtain complete resection. Two patients who had synchronous biliary malignant disease were excluded from this study. The remaining 28 patients formed the cohort of the present study. Their medical records were retrospectively reviewed. Results: Pancreatoduodenectomy (PD), gallbladder bed resection (GB) plus extrahepatic bile duct resection (EBD), GB plus PD, major hepatectomy (MH) plus EBD, and MH plus PD (HPD) were performed in 1, 1, 4, 14, and 8 patients, respectively. Histologically, 19 patients had regional lymph node metastasis (N), 4 had periaortic lymph node metastasis (PA-N), and 3 had distant metastasis other than PA-N (M). R0 resection was achieved in 20 (71%) patients. Five patients died of postoperative complications, and 3 of the 5 patients underwent HPD. The 5-year survival for the 23 patients who tolerated surgery was 33%; actually, 3 patients survived more than 5 years. There were no 5-year survivors in the patients who underwent HPD. Conclusion: There were only a few long-term survivors in patients with locally advanced gallbladder carcinoma who underwent combined PVR. Surgical indication of HPD with PVR should be carefully considered Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"predictive factors early recurrence patients distal cholangiocarcinoma pancreaticoduodenectomy read link google scholar","probabilities":0.9799733,"Title":"Predictive Factors Of Early Recurrence In Patients With Distal Cholangiocarcinoma After Pancreaticoduodenectomy","Abstract":"Read from the link","Source":"Google Scholar","category":"HUMAN","training_data":"Predictive Factors Of Early Recurrence In Patients With Distal Cholangiocarcinoma After Pancreaticoduodenectomy Read from the link Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"expression bcl 2 19 kda interacting protein 3 predicts prognosis ampullary carcinoma resection background adequate management strategy ampullary carcinoma ac rare neoplasm yet determined aim study identify specific molecular markers allowing adequate management ac methods clinicopathological data 41 patients underwent curative resection ac reviewed retrospectively expression thymidylate synthase ts bcl 2 19 kda interacting protein 3 bnip3 two sensitive markers 1 gemcitabine respectively evaluated immunohistochemically relationship expression levels markers clinicopathological data investigated results 5 year overall survival rate study population 62 univariate multivariate analyses lymph node metastasis neural invasion lymphatic invasion high level bnip3 expression significant predictive factors poor postoperative prognosis neither ts bnip3 expression able predict survival disease recurrence rate patients received postoperative adjuvant chemotherapy ac conclusions bnip3 expression may serve prognostic marker patients ac neither ts bnip3 contributes selection criteria adjuvant chemotherapy ac least respect current drug regimens pubmed","probabilities":0.9799733,"Title":"Expression of Bcl-2 19-kDa interacting protein 3 predicts prognosis after ampullary carcinoma resection","Abstract":"BACKGROUND: An adequate management strategy for ampullary carcinoma (AC), a rare neoplasm, has yet to be determined. The aim of this study was to identify specific molecular markers allowing for the adequate management of AC. METHODS: The clinicopathological data of 41 patients who underwent curative resection of AC were reviewed retrospectively. The expression of thymidylate synthase (TS) and Bcl-2 19-kDa interacting protein 3 (BNIP3), two sensitive markers for S-1 and gemcitabine, respectively, was evaluated immunohistochemically. The relationship between the expression levels of these markers and the clinicopathological data were then investigated. RESULTS: The 5-year overall survival rate in the study population was 62%. In univariate and multivariate analyses, lymph node metastasis, neural invasion, lymphatic invasion, and the high-level BNIP3 expression were significant predictive factors for a poor postoperative prognosis. Neither TS nor BNIP3 expression were able to predict survival or the disease recurrence rate in patients who received postoperative adjuvant chemotherapy for AC. CONCLUSIONS: BNIP3 expression may serve as a prognostic marker for patients with AC, but neither TS nor BNIP3 contributes to the selection criteria for adjuvant chemotherapy for AC, at least with respect to current drug regimens.","Source":"PubMed","category":"HUMAN","training_data":"Expression of Bcl-2 19-kDa interacting protein 3 predicts prognosis after ampullary carcinoma resection BACKGROUND: An adequate management strategy for ampullary carcinoma (AC), a rare neoplasm, has yet to be determined. The aim of this study was to identify specific molecular markers allowing for the adequate management of AC. METHODS: The clinicopathological data of 41 patients who underwent curative resection of AC were reviewed retrospectively. The expression of thymidylate synthase (TS) and Bcl-2 19-kDa interacting protein 3 (BNIP3), two sensitive markers for S-1 and gemcitabine, respectively, was evaluated immunohistochemically. The relationship between the expression levels of these markers and the clinicopathological data were then investigated. RESULTS: The 5-year overall survival rate in the study population was 62%. In univariate and multivariate analyses, lymph node metastasis, neural invasion, lymphatic invasion, and the high-level BNIP3 expression were significant predictive factors for a poor postoperative prognosis. Neither TS nor BNIP3 expression were able to predict survival or the disease recurrence rate in patients who received postoperative adjuvant chemotherapy for AC. CONCLUSIONS: BNIP3 expression may serve as a prognostic marker for patients with AC, but neither TS nor BNIP3 contributes to the selection criteria for adjuvant chemotherapy for AC, at least with respect to current drug regimens. PubMed","prediction_labels":"HUMAN"},{"cleaned":"immunomodulation inducible co stimulator icos human cytokine induced killer cells cholangiocarcinoma icos icos ligand interaction objective evaluate immunomodulation inducible co stimulator icos cytokine induced killer cik cells cholangiocarcinoma methods cik cells generated normal peripheral blood mononuclear cells methyl thiazolyl tetrazolium assay performed assess proliferation cik icos controlled cik cells elisa used analyze expression cytokines reverse transcription polymerase chain reaction immunohistochemistry performed evaluate expression icos ligand icosl cik cells human cholangiocarcinoma cell line qbc939 cells cytotoxicity cik cells determined either lactate dehydrogenase releasing assay vivo alteration tumor size prior treatment cik cells vivo results cik icos cells proliferated expressed higher secretion level interferon controlled cik cells exhibited higher cytotoxicity cholangiocarcinoma cell lines efficacy toxicity e ratios tested controlled cik cells importantly anti icosl antibody able attenuate elevated cytotoxicity mediated icos overexpression injected cholangiocarcinoma xenografts severe combined immunodeficiency mice cik icos cells survived better controlled cik cells around xenografts significantly reduced growth rate cholangiocarcinoma least volume increase severe necrosis xenografts controlled mice treated saline cik cik enhanced green fluorescent protein conclusion icos enhance cytotoxic effect cik cells cholangiocarcinoma vitro vivo effect mediated icos augmented cytokine secretion cell proliferation part icos icosl interaction stn","probabilities":0.9467213,"Title":"Immunomodulation Of Inducible Co-Stimulator (Icos) In Human Cytokine-Induced Killer Cells Against Cholangiocarcinoma Through Icos/Icos Ligand Interaction","Abstract":"Objective: To evaluate the immunomodulation of inducible co-stimulator (ICOS) in cytokine-induced killer (CIK) cells against cholangiocarcinoma. \r\n\r\n Methods: CIK cells were generated from normal peripheral blood mononuclear cells. Methyl thiazolyl tetrazolium assay was performed to assess proliferation of CIK-ICOS and controlled CIK cells; ELISA was used to analyze the expression of cytokines. Reverse transcription-polymerase chain reaction and immunohistochemistry were performed to evaluate the expression of ICOS ligand (ICOSL) in CIK cells and human cholangiocarcinoma cell line QBC939 cells. The cytotoxicity of CIK cells was determined either by lactate dehydrogenase-releasing assay in vivo or alteration of tumor size prior to and after the treatment of CIK cells in vivo. \r\n\r\n Results: CIK-ICOS cells proliferated more and expressed higher secretion a level of interferon-γ than the controlled CIK. These cells exhibited higher cytotoxicity against cholangiocarcinoma cell lines at all efficacy: toxicity (E:T) ratios tested than the controlled CIK cells. More importantly, the anti-ICOSL antibody was able to attenuate the elevated cytotoxicity mediated by ICOS overexpression. When injected into cholangiocarcinoma xenografts in severe combined immunodeficiency mice, CIK-ICOS cells survived better than the controlled CIK cells around xenografts and significantly reduced the growth rate of cholangiocarcinoma, with least volume increase and more severe necrosis of the xenografts than controlled mice treated with saline, CIK or CIK-enhanced green fluorescent protein. \r\n\r\n Conclusion: ICOS can enhance the cytotoxic effect of CIK cells against cholangiocarcinoma both in vitro and in vivo. This effect is mediated by ICOS-augmented cytokine secretion and cell proliferation, and in part through ICOS-ICOSL interaction.","Source":"STN","category":"ANIMAL","training_data":"Immunomodulation Of Inducible Co-Stimulator (Icos) In Human Cytokine-Induced Killer Cells Against Cholangiocarcinoma Through Icos/Icos Ligand Interaction Objective: To evaluate the immunomodulation of inducible co-stimulator (ICOS) in cytokine-induced killer (CIK) cells against cholangiocarcinoma. \r\n\r\n Methods: CIK cells were generated from normal peripheral blood mononuclear cells. Methyl thiazolyl tetrazolium assay was performed to assess proliferation of CIK-ICOS and controlled CIK cells; ELISA was used to analyze the expression of cytokines. Reverse transcription-polymerase chain reaction and immunohistochemistry were performed to evaluate the expression of ICOS ligand (ICOSL) in CIK cells and human cholangiocarcinoma cell line QBC939 cells. The cytotoxicity of CIK cells was determined either by lactate dehydrogenase-releasing assay in vivo or alteration of tumor size prior to and after the treatment of CIK cells in vivo. \r\n\r\n Results: CIK-ICOS cells proliferated more and expressed higher secretion a level of interferon-γ than the controlled CIK. These cells exhibited higher cytotoxicity against cholangiocarcinoma cell lines at all efficacy: toxicity (E:T) ratios tested than the controlled CIK cells. More importantly, the anti-ICOSL antibody was able to attenuate the elevated cytotoxicity mediated by ICOS overexpression. When injected into cholangiocarcinoma xenografts in severe combined immunodeficiency mice, CIK-ICOS cells survived better than the controlled CIK cells around xenografts and significantly reduced the growth rate of cholangiocarcinoma, with least volume increase and more severe necrosis of the xenografts than controlled mice treated with saline, CIK or CIK-enhanced green fluorescent protein. \r\n\r\n Conclusion: ICOS can enhance the cytotoxic effect of CIK cells against cholangiocarcinoma both in vitro and in vivo. This effect is mediated by ICOS-augmented cytokine secretion and cell proliferation, and in part through ICOS-ICOSL interaction. STN","prediction_labels":"ANIMAL"},{"cleaned":"gallbladder carcinoma surgical management gallblad der carcinoma analysis 37 cases background aims gallbladder carcinoma rare yet aggressive cancer study evaluate presentation staging procedures complications survival patients gallbladder carcinoma material methods data presentation operative findings postoperative evolution complications survival data analyzed 37 patients gallbladder carcinoma cohort study confirmed histopathology january 2005 december 2011 surgical department regional institute gastroenterology hepatology octavian fodor cluj napoca romania results 12 cases suspicion gbc gallbladder carcinoma surgery 6 cases gbc suspected intraoperatory 19 cases histopathology exam radical cholecystectomy considered 9 cases 24 32 4 cases cholecystectomy alone patients tis t1 5 cases liver resection associated conclusion gbc low incidence 0 35 cholecystectomies females affected f b 4 3 1 gbc associated low resecability rate 24 32 bad prognosis survival year stages t3 t4 cases diagnosis hidden acute inflammatory process acute cholecystitis diagnosis made surgical intervention therefore histopathology crucial situations key words gallbladder carcinoma jaundice palliative treatment resection survival pubmed","probabilities":0.9799733,"Title":"Gallbladder carcinoma Surgical management of gallblad-der carcinoma An analysis of 37 cases","Abstract":"BACKGROUND & AIMS: Gallbladder carcinoma is a rare yet very aggressive cancer. In this study we evaluate the presentation, staging, procedures, complications and survival of patients with gallbladder carcinoma. MATERIAL AND METHODS: Data at presentation, operative findings, postoperative evolution, complications and survival data were analyzed for 37 patients with gallbladder carcinoma (as cohort study) confirmed at histopathology between January 2005 and December 2011 in Surgical Department of Regional Institute of Gastroenterology And Hepatology \"Octavian Fodor\" Cluj-Napoca, Romania. RESULTS: In 12 cases we had the suspicion of GBC (gallbladder carcinoma) before surgery, in 6 cases GBC was suspected intraoperatory and in 19 cases only after the histopathology exam. Radical cholecystectomy was considered in 9 cases (24.32%): 4 cases with cholecystectomy alone (patients with Tis-T1) and in 5 cases liver resection was associated. CONCLUSION: The GBC has a low incidence (0.35% out of all cholecystectomies), the females being more affected (F:B=4.3:1). GBC was associated with low resecability rate (24.32%) and having a bad prognosis (survival under a year in stages T3 and T4). In most cases the diagnosis was hidden by an acute inflammatory process (acute cholecystitis) and the diagnosis was made after surgical intervention, therefore, the histopathology is crucial in these situations. KEY WORDS: Gallbladder carcinoma, Jaundice, Palliative treatment, Resection, Survival.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder carcinoma Surgical management of gallblad-der carcinoma An analysis of 37 cases BACKGROUND & AIMS: Gallbladder carcinoma is a rare yet very aggressive cancer. In this study we evaluate the presentation, staging, procedures, complications and survival of patients with gallbladder carcinoma. MATERIAL AND METHODS: Data at presentation, operative findings, postoperative evolution, complications and survival data were analyzed for 37 patients with gallbladder carcinoma (as cohort study) confirmed at histopathology between January 2005 and December 2011 in Surgical Department of Regional Institute of Gastroenterology And Hepatology \"Octavian Fodor\" Cluj-Napoca, Romania. RESULTS: In 12 cases we had the suspicion of GBC (gallbladder carcinoma) before surgery, in 6 cases GBC was suspected intraoperatory and in 19 cases only after the histopathology exam. Radical cholecystectomy was considered in 9 cases (24.32%): 4 cases with cholecystectomy alone (patients with Tis-T1) and in 5 cases liver resection was associated. CONCLUSION: The GBC has a low incidence (0.35% out of all cholecystectomies), the females being more affected (F:B=4.3:1). GBC was associated with low resecability rate (24.32%) and having a bad prognosis (survival under a year in stages T3 and T4). In most cases the diagnosis was hidden by an acute inflammatory process (acute cholecystitis) and the diagnosis was made after surgical intervention, therefore, the histopathology is crucial in these situations. KEY WORDS: Gallbladder carcinoma, Jaundice, Palliative treatment, Resection, Survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"genomic transcriptional alterations cholangiocarcinoma cholangiocarcinoma cca one representative cancers refractory therapeutic approach incidence cca highest northeastern part thailand chronic inflammation caused liver fluke opisthorchis viverrini ov infection major etiologic factor incidence cca also increasing countries including japan overview genetic transcriptional alterations cca without association ov infection cca ov shows enhanced expression genes involved xenobiotic metabolism chronic inflammatory responses including cytokine signaling whereas cca without ov shows enhanced expression growth factor signaling her2 exome following prevalence sequencing identified mutations bap1 arid1a idh1 idh2 genes cca addition high incidence known mutations tp53 kras2 smad4 cdkn2a genes suggesting role chromatin modulators cca pathogenesis cca ov shows significantly higher incidence tp53 gene mutation whereas cca without ov showed significantly frequent mutations bap1 idh1 idh2 genes however ccas ov without ov share similar mutation spectrum dominated c g transitions mainly cpg dinucleotides suggesting cca shares etiologic factors pancreatic ductal carcinoma hepatocellular carcinoma comprehensive analyses genetic transcriptional alterations cca without ov infection provide useful information prevention early diagnosis treatment cca pubmed","probabilities":0.9799733,"Title":"Genomic and transcriptional alterations of cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is one of the representative cancers refractory to any therapeutic approach. The incidence of CCA is highest in the northeastern part of Thailand, where chronic inflammation caused by liver fluke (Opisthorchis viverrini: Ov) infection is a major etiologic factor. The incidence of CCA is also increasing in other countries, including Japan. Here, we overview the genetic and transcriptional alterations of CCA with and without association with Ov infection. CCA with Ov shows enhanced expression of the genes involved in xenobiotic metabolism and chronic inflammatory responses, including cytokine signaling, whereas CCA without Ov shows enhanced expression of growth factor signaling, such as HER2. Exome and the following prevalence sequencing identified mutations of the BAP1, ARID1A, IDH1 and IDH2 genes in CCA, in addition to the high incidence of known mutations in the TP53, KRAS2 SMAD4, and CDKN2A genes, suggesting the role of chromatin modulators in CCA pathogenesis. CCA with Ov shows significantly higher incidence of the TP53 gene mutation, whereas CCA without Ov showed significantly more frequent mutations of the BAP1, IDH1 and IDH2 genes. However, CCAs with Ov and without Ov share a similar mutation spectrum dominated by C : G > T : A transitions mainly at CpG dinucleotides, suggesting that CCA shares etiologic factors with pancreatic ductal carcinoma but not with hepatocellular carcinoma. Comprehensive analyses of the genetic and transcriptional alterations of CCA with and without Ov infection would provide useful information for the prevention, early diagnosis, and treatment of CCA.","Source":"PubMed","category":"HUMAN","training_data":"Genomic and transcriptional alterations of cholangiocarcinoma Cholangiocarcinoma (CCA) is one of the representative cancers refractory to any therapeutic approach. The incidence of CCA is highest in the northeastern part of Thailand, where chronic inflammation caused by liver fluke (Opisthorchis viverrini: Ov) infection is a major etiologic factor. The incidence of CCA is also increasing in other countries, including Japan. Here, we overview the genetic and transcriptional alterations of CCA with and without association with Ov infection. CCA with Ov shows enhanced expression of the genes involved in xenobiotic metabolism and chronic inflammatory responses, including cytokine signaling, whereas CCA without Ov shows enhanced expression of growth factor signaling, such as HER2. Exome and the following prevalence sequencing identified mutations of the BAP1, ARID1A, IDH1 and IDH2 genes in CCA, in addition to the high incidence of known mutations in the TP53, KRAS2 SMAD4, and CDKN2A genes, suggesting the role of chromatin modulators in CCA pathogenesis. CCA with Ov shows significantly higher incidence of the TP53 gene mutation, whereas CCA without Ov showed significantly more frequent mutations of the BAP1, IDH1 and IDH2 genes. However, CCAs with Ov and without Ov share a similar mutation spectrum dominated by C : G > T : A transitions mainly at CpG dinucleotides, suggesting that CCA shares etiologic factors with pancreatic ductal carcinoma but not with hepatocellular carcinoma. Comprehensive analyses of the genetic and transcriptional alterations of CCA with and without Ov infection would provide useful information for the prevention, early diagnosis, and treatment of CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"il17 producing cells induce angiogenesis associated poor survival gallbladder cancer patients despite conventional treatment modalities gallbladder cancer gbc remains highly lethal malignancy prognostic biomarkers effective adjuvant immunotherapy gbc available recent past immunotherapeutic approaches targeting tumor associated inflammation gained importance mediators inflammatory circuit remain unexplored gbc patients current prospective study investigated role il17 producing tcr 17 cd4 th17 cd8 tc17 regulatory cells tregs pathogenesis gbc analysis multi color flow cytometry revealed compared healthy individuals hi 17 th17 tc17 cells increased peripheral blood mononuclear cells pbmcs tumor infiltrating lymphocytes til gbc patients tregs decreased pbmcs increased tils gbc patients suppressive potential tregs gbc patients hi comparable serum cytokines profile gbc patients showed elevated levels cytokines il6 il23 il1 required polarization stabilization il17 producing cells demonstrated 17 cells migrate toward tumor bed using cxcl9 cxcr3 axis il17 secreted 17 induced productions vascular endothelial growth factor angiogenesis related factors gbc cells 17 cells promote vasculogenesis studied chick chorioallantoic membrane assay survival analysis showed 17 th17 treg cells peripheral blood associated poor survival gbc patients findings suggest 17 protumorigenic subtype cells induces angiogenesis 17 may considered predictive biomarker gbc thus opening avenues targeted therapies pubmed","probabilities":0.9799733,"Title":"IL17 producing γδT cells induce angiogenesis and are associated with poor survival in gallbladder cancer patients","Abstract":"Despite conventional treatment modalities, gallbladder cancer (GBC) remains a highly lethal malignancy. Prognostic biomarkers and effective adjuvant immunotherapy for GBC are not available. In the recent past, immunotherapeutic approaches targeting tumor associated inflammation have gained importance but the mediators of inflammatory circuit remain unexplored in GBC patients. In the current prospective study, we investigated the role of IL17 producing TCRγδ(+) (Tγδ17), CD4(+) (Th17), CD8(+) (Tc17) and regulatory T cells (Tregs) in pathogenesis of GBC. Analysis by multi-color flow cytometry revealed that compared to healthy individuals (HI), Tγδ17, Th17 and Tc17 cells were increased in peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TIL) of GBC patients. Tregs were decreased in PBMCs but increased in TILs of GBC patients. The suppressive potential of Tregs from GBC patients and HI were comparable. Serum cytokines profile of GBC patients showed elevated levels of cytokines (IL6, IL23 and IL1β) required for polarization and/or stabilization of IL17 producing cells. We demonstrated that Tγδ17 cells migrate toward tumor bed using CXCL9-CXCR3 axis. IL17 secreted by Tγδ17 induced productions of vascular endothelial growth factor and other angiogenesis related factors in GBC cells. Tγδ17 cells promote vasculogenesis as studied by chick chorioallantoic membrane assay. Survival analysis showed that Tγδ17, Th17 and Treg cells in peripheral blood were associated with poor survival of GBC patients. Our findings suggest that Tγδ17 is a protumorigenic subtype of γδT cells which induces angiogenesis. Tγδ17 may be considered as a predictive biomarker in GBC thus opening avenues for targeted therapies.","Source":"PubMed","category":"HUMAN","training_data":"IL17 producing γδT cells induce angiogenesis and are associated with poor survival in gallbladder cancer patients Despite conventional treatment modalities, gallbladder cancer (GBC) remains a highly lethal malignancy. Prognostic biomarkers and effective adjuvant immunotherapy for GBC are not available. In the recent past, immunotherapeutic approaches targeting tumor associated inflammation have gained importance but the mediators of inflammatory circuit remain unexplored in GBC patients. In the current prospective study, we investigated the role of IL17 producing TCRγδ(+) (Tγδ17), CD4(+) (Th17), CD8(+) (Tc17) and regulatory T cells (Tregs) in pathogenesis of GBC. Analysis by multi-color flow cytometry revealed that compared to healthy individuals (HI), Tγδ17, Th17 and Tc17 cells were increased in peripheral blood mononuclear cells (PBMCs) and tumor infiltrating lymphocytes (TIL) of GBC patients. Tregs were decreased in PBMCs but increased in TILs of GBC patients. The suppressive potential of Tregs from GBC patients and HI were comparable. Serum cytokines profile of GBC patients showed elevated levels of cytokines (IL6, IL23 and IL1β) required for polarization and/or stabilization of IL17 producing cells. We demonstrated that Tγδ17 cells migrate toward tumor bed using CXCL9-CXCR3 axis. IL17 secreted by Tγδ17 induced productions of vascular endothelial growth factor and other angiogenesis related factors in GBC cells. Tγδ17 cells promote vasculogenesis as studied by chick chorioallantoic membrane assay. Survival analysis showed that Tγδ17, Th17 and Treg cells in peripheral blood were associated with poor survival of GBC patients. Our findings suggest that Tγδ17 is a protumorigenic subtype of γδT cells which induces angiogenesis. Tγδ17 may be considered as a predictive biomarker in GBC thus opening avenues for targeted therapies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term survival recurrent intrahepatic cholangiocarcinoma impact selection repeat surgery background definitive guidelines recurrent intrahepatic cholangiocarcinoma icc exist study focused repeat surgery analyzing survival outcomes recurrent icc evaluated relationship clinicopathological features primary tumor implementation repeat surgery identify potential selection criteria methods total 108 patients recurrent icc 1993 2015 analyzed 15 patients underwent repeat surgery 93 results seven 29 patients intrahepatic recurrence eight 44 patients extrahepatic recurrence amenable repeat surgery thirty five patients simultaneous consequent intrahepatic recurrence extrahepatic recurrence amenable repeat surgery patients underwent repeat surgery lower proportion lymph node metastases n 0 0 vs n 47 50 5 p 0 001 multiple tumors primary tumor n 1 6 7 vs n 31 33 3 p 0 037 early recurrence 1 year n 4 26 7 vs n 62 66 7 p 0 003 survival recurrence sar better patients underwent repeat surgery median sar time 91 6 vs 10 4 months 3 year survival 86 7 vs 8 7 respectively p 0 001 conclusions repeat surgery recurrent icc appropriate selection associated prolonged survival regarding feasibility nodal status number tumors primary tumor time recurrence may considered selection criteria stn","probabilities":0.9799733,"Title":"Long-Term Survival Of Recurrent Intrahepatic Cholangiocarcinoma: The Impact And Selection Of Repeat Surgery","Abstract":"Background: Definitive guidelines for recurrent intrahepatic cholangiocarcinoma (ICC) do not exist. This study has focused on the repeat surgery when analyzing the survival outcomes of recurrent ICC. We evaluated the relationship between clinicopathological features of the primary tumor and implementation of the repeat surgery to identify its potential selection criteria. \r\n\r\n Methods: A total of 108 patients with recurrent ICC between 1993 and 2015 were analyzed. Of these, 15 patients underwent repeat surgery and 93 did not. \r\n\r\n Results: Seven out of 29 patients with intrahepatic recurrence and eight out of 44 patients with extrahepatic recurrence were amenable to the repeat surgery. Thirty-five patients with simultaneous or consequent intrahepatic recurrence and extrahepatic recurrence were not amenable to the repeat surgery. Patients who underwent repeat surgery had a lower proportion of lymph node metastases (n = 0 [0%] vs. n = 47 [50.5%], p < 0.001), multiple tumors in the primary tumor (n = 1 [6.7%] vs. n = 31 [33.3%], p = 0.037), or early recurrence (≤ 1 year; n = 4 [26.7%] vs. n = 62 [66.7%], p = 0.003). Survival after recurrence (SAR) was better in patients who underwent repeat surgery than in those who did not (median SAR time: 91.6 vs. 10.4 months, and 3-year survival: 86.7 vs. 8.7%, respectively, p < 0.001). \r\n\r\n Conclusions: Repeat surgery for recurrent ICC with an appropriate selection can be associated with prolonged survival. Regarding the feasibility, nodal status, number of tumors on the primary tumor, and time to recurrence may be considered as selection criteria.","Source":"STN","category":"HUMAN","training_data":"Long-Term Survival Of Recurrent Intrahepatic Cholangiocarcinoma: The Impact And Selection Of Repeat Surgery Background: Definitive guidelines for recurrent intrahepatic cholangiocarcinoma (ICC) do not exist. This study has focused on the repeat surgery when analyzing the survival outcomes of recurrent ICC. We evaluated the relationship between clinicopathological features of the primary tumor and implementation of the repeat surgery to identify its potential selection criteria. \r\n\r\n Methods: A total of 108 patients with recurrent ICC between 1993 and 2015 were analyzed. Of these, 15 patients underwent repeat surgery and 93 did not. \r\n\r\n Results: Seven out of 29 patients with intrahepatic recurrence and eight out of 44 patients with extrahepatic recurrence were amenable to the repeat surgery. Thirty-five patients with simultaneous or consequent intrahepatic recurrence and extrahepatic recurrence were not amenable to the repeat surgery. Patients who underwent repeat surgery had a lower proportion of lymph node metastases (n = 0 [0%] vs. n = 47 [50.5%], p < 0.001), multiple tumors in the primary tumor (n = 1 [6.7%] vs. n = 31 [33.3%], p = 0.037), or early recurrence (≤ 1 year; n = 4 [26.7%] vs. n = 62 [66.7%], p = 0.003). Survival after recurrence (SAR) was better in patients who underwent repeat surgery than in those who did not (median SAR time: 91.6 vs. 10.4 months, and 3-year survival: 86.7 vs. 8.7%, respectively, p < 0.001). \r\n\r\n Conclusions: Repeat surgery for recurrent ICC with an appropriate selection can be associated with prolonged survival. Regarding the feasibility, nodal status, number of tumors on the primary tumor, and time to recurrence may be considered as selection criteria. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact lymph node metastasis distal cholangiocarcinoma background aim study investigate prognostic impact lymph node metastasis cholangiocarcinoma using three different classifications methods patients underwent pancreaticoduodenectomy distal cholangiocarcinoma 24 hospitals japan 2001 2010 included survival calculated means kaplan meier method differences subgroups assessed log rank test cox proportional hazards model used identify independent predictors survival 2 scores calculated determine cut value number involved nodes lymph node ratio lnr total lymph node count tlnc discriminating survival results 370 patients included median range tlnc 19 3 59 nodal metastasis occurred 157 patients 42 4 per cent median range number involved nodes lnr 2 1 19 0 11 0 02 0 80 respectively four involved nodes associated significantly shorter median survival 1 3 versus 2 2 years p 0 001 lnr least 0 17 1 4 versus 2 3 years p 0 002 involvement nodes along common hepatic artery present 21 patients 13 4 per cent also associated shorter survival median 1 3 versus 2 1 years p 0 046 multivariable analysis among 157 node positive patients identified number involved nodes independent prognostic factor risk ratio 1 87 p 0 002 conclusion number involved nodes strong predictor survival patients distal cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic impact of lymph node metastasis in distal cholangiocarcinoma","Abstract":"BACKGROUND: The aim of the study was to investigate the prognostic impact of lymph node metastasis in cholangiocarcinoma using three different classifications. METHODS: Patients who underwent pancreaticoduodenectomy for distal cholangiocarcinoma in 24 hospitals in Japan between 2001 and 2010 were included. Survival was calculated by means of the Kaplan-Meier method and differences between subgroups were assessed with the log rank test. The Cox proportional hazards model was used to identify independent predictors of survival. χ(2) scores were calculated to determine the cut-off value of the number of involved nodes, lymph node ratio (LNR) and total lymph node count (TLNC) for discriminating survival. RESULTS: Some 370 patients were included. The median (range) TLNC was 19 (3-59). Nodal metastasis occurred in 157 patients (42·4 per cent); the median (range) number of involved nodes and LNR were 2 (1-19) and 0·11 (0·02-0·80) respectively. Four or more involved nodes was associated with a significantly shorter median survival (1·3 versus 2·2 years; P = 0·001), as was a LNR of at least 0·17 (1·4 versus 2·3 years; P = 0·002). Involvement of nodes along the common hepatic artery, present in 21 patients (13·4 per cent), was also associated with a shorter survival (median 1·3 versus 2·1 years; P = 0·046). Multivariable analysis among 157 node-positive patients identified the number of involved nodes as an independent prognostic factor (risk ratio 1·87; P = 0·002). CONCLUSION: The number of involved nodes was a strong predictor of survival in patients with distal cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic impact of lymph node metastasis in distal cholangiocarcinoma BACKGROUND: The aim of the study was to investigate the prognostic impact of lymph node metastasis in cholangiocarcinoma using three different classifications. METHODS: Patients who underwent pancreaticoduodenectomy for distal cholangiocarcinoma in 24 hospitals in Japan between 2001 and 2010 were included. Survival was calculated by means of the Kaplan-Meier method and differences between subgroups were assessed with the log rank test. The Cox proportional hazards model was used to identify independent predictors of survival. χ(2) scores were calculated to determine the cut-off value of the number of involved nodes, lymph node ratio (LNR) and total lymph node count (TLNC) for discriminating survival. RESULTS: Some 370 patients were included. The median (range) TLNC was 19 (3-59). Nodal metastasis occurred in 157 patients (42·4 per cent); the median (range) number of involved nodes and LNR were 2 (1-19) and 0·11 (0·02-0·80) respectively. Four or more involved nodes was associated with a significantly shorter median survival (1·3 versus 2·2 years; P = 0·001), as was a LNR of at least 0·17 (1·4 versus 2·3 years; P = 0·002). Involvement of nodes along the common hepatic artery, present in 21 patients (13·4 per cent), was also associated with a shorter survival (median 1·3 versus 2·1 years; P = 0·046). Multivariable analysis among 157 node-positive patients identified the number of involved nodes as an independent prognostic factor (risk ratio 1·87; P = 0·002). CONCLUSION: The number of involved nodes was a strong predictor of survival in patients with distal cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder cancer management gallbladder cancer gbc represents 3 8 gastrointestinal cancers usually known poor prognosis 0 2 2 9 cases cancer found cholecystectomy specimens better understanding spread mode tumor helps better surgical management aim present review underline management gbc based comprehension risk factors anatomic features medline pubmed database search performed identify articles published 2000 2011 using keywords carcinoma gallbladder incidental gallbladder cancer gallbladder neoplasm cholecystectomy pathological situations chronic lithiasis biliopancreatic junction abnormalities clearly identified predisposing gbc laparoscopy increases peritoneal parietal tumor dissemination thus performed gbc suspected determinant prognostic factors nodal perineural venous involvement invasion cystic duct tumor differentiation simple cholecystectomy sufficient tumors classified t1a cancers exceeding muscularis radical re resection required due high risk recurrence aggressive surgery improved overall survival patients still standard adjuvant treatment patients included prospective trials google scholar","probabilities":0.9799733,"Title":"Incidental Gallbladder Cancer: What Management?","Abstract":"Gallbladder cancer (GBC) represents 3.8% of all gastrointestinal cancers and usually known to be of a poor prognosis. In 0.2–2.9% of cases, this cancer is found in cholecystectomy specimens. A better understanding of spread mode of this tumor helps a better surgical management. The aim of the present review is to underline the management of GBC based on the comprehension of risk factors and anatomic features. A Medline, PubMed database search was performed to identify articles published from 2000 to 2011 using the keywords ‘carcinoma of gallbladder’, ‘incidental gallbladder cancer’, ‘gallbladder neoplasm’ and ‘cholecystectomy’. Some pathological situations such as chronic lithiasis and biliopancreatic junction abnormalities have been clearly identified as predisposing to GBC. Laparoscopy increases peritoneal and parietal tumor dissemination, thus, it should not be performed when GBC is suspected. Most determinant prognostic factors are nodal, perineural and venous involvement, invasion of the cystic duct and the tumor differentiation. The simple cholecystectomy is sufficient for tumors classified as T1a; for other cancers exceeding the muscularis, radical re-resection is required due to the high risk of recurrence. This aggressive surgery improved the overall survival of patients. There is still no standard adjuvant treatment; patients should be included in prospective trials.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidental Gallbladder Cancer: What Management? Gallbladder cancer (GBC) represents 3.8% of all gastrointestinal cancers and usually known to be of a poor prognosis. In 0.2–2.9% of cases, this cancer is found in cholecystectomy specimens. A better understanding of spread mode of this tumor helps a better surgical management. The aim of the present review is to underline the management of GBC based on the comprehension of risk factors and anatomic features. A Medline, PubMed database search was performed to identify articles published from 2000 to 2011 using the keywords ‘carcinoma of gallbladder’, ‘incidental gallbladder cancer’, ‘gallbladder neoplasm’ and ‘cholecystectomy’. Some pathological situations such as chronic lithiasis and biliopancreatic junction abnormalities have been clearly identified as predisposing to GBC. Laparoscopy increases peritoneal and parietal tumor dissemination, thus, it should not be performed when GBC is suspected. Most determinant prognostic factors are nodal, perineural and venous involvement, invasion of the cystic duct and the tumor differentiation. The simple cholecystectomy is sufficient for tumors classified as T1a; for other cancers exceeding the muscularis, radical re-resection is required due to the high risk of recurrence. This aggressive surgery improved the overall survival of patients. There is still no standard adjuvant treatment; patients should be included in prospective trials. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"high incidence colorectal cancer finnish patients concomitant inflammatory bowel disease primary sclerosing cholangitis background increased risk colorectal cancer reported worldwide patients comorbidity ammatory bowel diseases ibd primary sclerosing cholangitis psc risk ratio 4 9 27 1 1 4 report incidence colorectal cancer finnish patients ibd psc methods data based prospective ibd register catchment area follow covered years 1986 2007 population based cohort comprised 1915 adult patients 1254 ulcerative colitis 550 crohn diseased 111 ammatory bowel disease unclassi ed altogether 45 2 4 patients concomitant psc 45 patients 10 22 patients underwent colectomy 9 20 liver transplantation results 45 patients ibd psc 7 developed cholangiocarcinoma 3 colorectal carcinoma standardised incidence ratio sir colorectal carcinoma 33 91 observed 3 expected 0 1 compared population 95 ci 6 99 99 10 incidence cholangiocarcinoma gall bladder cancer 3 100 000 inhabitants finland means risk cholangiocarcinoma ibd cohort least 500 fold conclusions risk colorectal cancer one highest reported despite con dence intervals broad risk cholangiocarcinoma seems much higher reference 1 claessen mm 2009 high lifetime risk cancer primary sclerosing cholangitis 2 jess 2006 incidence prevalence colorectal dysplasia ammatory bowel disease populationbased study olmsted county minnesota 3 lakatos l 2006 risk factors ulcerative colitisassociated colorectal cancer hungarian cohort patients ulcerative colitis results populationbased study 4 sokol h 2008 disease activity cancer risk ammatory bowel disease associated primary sclerosing cholangitis google scholar","probabilities":0.9799733,"Title":"High Incidence Of Colorectal Cancer In Finnish Patients With Concomitant Inflammatory Bowel Disease And Primary Sclerosing Cholangitis","Abstract":"Background: An increased risk of colorectal cancer has been reported worldwide in patients with comorbidity of inflammatory bowel diseases (IBD) and primary sclerosing cholangitis (PSC), the risk ratio being 4.9 27.1 [1 4]. We report the incidence of colorectal cancer in Finnish patients with both IBD and PSC. Methods: The data were based on a prospective IBD register in our catchment area; the follow-up covered years 1986 2007. This population based cohort comprised 1915 adult patients, 1254 with ulcerative colitis, 550 with Crohn’s diseased, and 111 with inflammatory bowel disease unclassified. Altogether 45 (2.4%) patients had concomitant PSC. Of these 45 patients, 10 (22%) patients had underwent colectomy, and 9 (20%) liver transplantation.Results: Of the 45 patients with IBD and PSC, 7 developed cholangiocarcinoma and 3 colorectal carcinoma. The standardised incidence ratio (SIR) for colorectal carcinoma was 33.91 (observed 3/expected 0.1 compared to the population; 95% CI 6.99 99.10). The incidence of cholangiocarcinoma and gall bladder cancer is 3/100,000 inhabitants in Finland, which means that the risk for cholangiocarcinoma in our IBD cohort is at least 500-fold. Conclusions: The risk of colorectal cancer was one of the highest reported, despite confidence intervals were broad. The risk of cholangiocarcinoma seems to be much higher. Reference(s) [1] Claessen, MM (2009), High lifetime risk of cancer in primary sclerosing cholangitis. [2] Jess T (2006), Incidence and prevalence of colorectal dysplasia in inflammatory bowel disease: A populationbased study in Olmsted County, Minnesota. [3] Lakatos, L (2006), Risk factors of ulcerative colitisassociated colorectal cancer in a Hungarian cohort of patients with ulcerative colitis: results of a populationbased study. [4] Sokol H (2008), Disease activity and cancer risk in inflammatory bowel disease associated with primary sclerosing cholangitis","Source":"Google Scholar","category":"HUMAN","training_data":"High Incidence Of Colorectal Cancer In Finnish Patients With Concomitant Inflammatory Bowel Disease And Primary Sclerosing Cholangitis Background: An increased risk of colorectal cancer has been reported worldwide in patients with comorbidity of inflammatory bowel diseases (IBD) and primary sclerosing cholangitis (PSC), the risk ratio being 4.9 27.1 [1 4]. We report the incidence of colorectal cancer in Finnish patients with both IBD and PSC. Methods: The data were based on a prospective IBD register in our catchment area; the follow-up covered years 1986 2007. This population based cohort comprised 1915 adult patients, 1254 with ulcerative colitis, 550 with Crohn’s diseased, and 111 with inflammatory bowel disease unclassified. Altogether 45 (2.4%) patients had concomitant PSC. Of these 45 patients, 10 (22%) patients had underwent colectomy, and 9 (20%) liver transplantation.Results: Of the 45 patients with IBD and PSC, 7 developed cholangiocarcinoma and 3 colorectal carcinoma. The standardised incidence ratio (SIR) for colorectal carcinoma was 33.91 (observed 3/expected 0.1 compared to the population; 95% CI 6.99 99.10). The incidence of cholangiocarcinoma and gall bladder cancer is 3/100,000 inhabitants in Finland, which means that the risk for cholangiocarcinoma in our IBD cohort is at least 500-fold. Conclusions: The risk of colorectal cancer was one of the highest reported, despite confidence intervals were broad. The risk of cholangiocarcinoma seems to be much higher. Reference(s) [1] Claessen, MM (2009), High lifetime risk of cancer in primary sclerosing cholangitis. [2] Jess T (2006), Incidence and prevalence of colorectal dysplasia in inflammatory bowel disease: A populationbased study in Olmsted County, Minnesota. [3] Lakatos, L (2006), Risk factors of ulcerative colitisassociated colorectal cancer in a Hungarian cohort of patients with ulcerative colitis: results of a populationbased study. [4] Sokol H (2008), Disease activity and cancer risk in inflammatory bowel disease associated with primary sclerosing cholangitis Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"recurrent gallbladder carcinoma presenting malignant ascites abstract available google scholar","probabilities":0.9799733,"Title":"Recurrent Gallbladder Carcinoma Presenting with Malignant Ascites","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Recurrent Gallbladder Carcinoma Presenting with Malignant Ascites Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"risk factors intrahepatic extrahepatic cholangiocarcinoma systematic review meta analysis background aims cholangiocarcinoma cca carries poor prognosis increasing incidence causes poorly understood although risk factors known vary globally collectively account minority cases aim study perform comprehensive meta analysis risk factors intrahepatic icca extrahepatic cholangiocarcinoma ecca eastern western world studies methods literature search case control studies performed identify potential risk factors icca ecca pooled odds ratios ors 95 cis heterogeneity calculated funnel plots used assess publication bias meta regression used select risk factors comparison eastern western studies results total 13 risk factors selected 25 case control studies 7 geographically diverse countries strongest risk factors icca ecca biliary cysts stones cirrhosis hepatitis b hepatitis c choledochal cysts conferred greatest risk icca ecca pooled ors 26 71 95 ci 15 80 45 16 34 94 24 36 50 12 respectively significant associations found hypertension obesity either icca ecca comparing eastern western populations difference association hepatitis b icca coefficient 0 15195 95 ci 0 278 0 025 p 0 022 conclusion comprehensive meta analysis cca risk factors date risk factors diabetes although less strong increasing globally may contributing rising rates cancer lay summary cholangiocarcinoma cca cancer arising bile ducts inside intrahepatic cca connected liver extrahepatic cca aggressive cancer 95 patients die within 5 years cca rates increasing globally causes cca poorly understood risk factors known account minority cases study found strongest risk factors intrahepatic extrahepatic cca cysts stones bile ducts cirrhosis hepatitis b c viruses risk factors cca diabetes although less strong increasing globally may contributing rising rates cca google scholar","probabilities":0.9799733,"Title":"Risk Factors For Intrahepatic And Extrahepatic Cholangiocarcinoma: A Systematic Review And Meta-Analysis","Abstract":"Background & aims: Cholangiocarcinoma (CCA) carries a poor prognosis, is increasing in incidence and its causes are poorly understood. Although some risk factors are known, they vary globally and collectively account for a minority of cases. The aim of this study was to perform a comprehensive meta-analysis of risk factors for intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA), from Eastern and Western world studies. \nMethods: A literature search of case-control studies was performed to identify potential risk factors for iCCA and eCCA. Pooled odds ratios (ORs) with 95% CIs and heterogeneity were calculated. Funnel plots were used to assess publication bias, and meta-regression was used to select risk factors for comparison between Eastern and Western studies. \nResults: A total of 13 risk factors were selected from 25 case-control studies in 7 geographically diverse countries. The strongest risk factors for both iCCA and eCCA were biliary cysts and stones, cirrhosis, hepatitis B and hepatitis C. Choledochal cysts conferred the greatest risk of both iCCA and eCCA with pooled ORs of 26.71 (95% CI 15.80-45.16) and 34.94 (24.36-50.12), respectively. No significant associations were found between hypertension and obesity for either iCCA or eCCA. Comparing Eastern and Western populations, there was a difference for the association of hepatitis B with iCCA (coefficient = -0.15195; 95% CI -0.278 to -0.025; p = 0.022). \nConclusion: This is the most comprehensive meta-analysis of CCA risk factors to date. Some risk factors, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of this cancer. \nLay summary: Cholangiocarcinoma (CCA) is a cancer arising in the bile ducts inside (intrahepatic CCA) and connected to the liver (extrahepatic CCA). It is a very aggressive cancer: 95% of patients die within 5 years. CCA rates are increasing globally, but the causes of CCA are poorly understood. The few risk factors that are known account for only a minority of cases. In this study, we found that the strongest risk factors for both intrahepatic and extrahepatic CCA are cysts and stones in the bile ducts, cirrhosis, and hepatitis B and C viruses. Some risk factors for CCA, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of CCA.","Source":"Google Scholar","category":"HUMAN","training_data":"Risk Factors For Intrahepatic And Extrahepatic Cholangiocarcinoma: A Systematic Review And Meta-Analysis Background & aims: Cholangiocarcinoma (CCA) carries a poor prognosis, is increasing in incidence and its causes are poorly understood. Although some risk factors are known, they vary globally and collectively account for a minority of cases. The aim of this study was to perform a comprehensive meta-analysis of risk factors for intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA), from Eastern and Western world studies. \nMethods: A literature search of case-control studies was performed to identify potential risk factors for iCCA and eCCA. Pooled odds ratios (ORs) with 95% CIs and heterogeneity were calculated. Funnel plots were used to assess publication bias, and meta-regression was used to select risk factors for comparison between Eastern and Western studies. \nResults: A total of 13 risk factors were selected from 25 case-control studies in 7 geographically diverse countries. The strongest risk factors for both iCCA and eCCA were biliary cysts and stones, cirrhosis, hepatitis B and hepatitis C. Choledochal cysts conferred the greatest risk of both iCCA and eCCA with pooled ORs of 26.71 (95% CI 15.80-45.16) and 34.94 (24.36-50.12), respectively. No significant associations were found between hypertension and obesity for either iCCA or eCCA. Comparing Eastern and Western populations, there was a difference for the association of hepatitis B with iCCA (coefficient = -0.15195; 95% CI -0.278 to -0.025; p = 0.022). \nConclusion: This is the most comprehensive meta-analysis of CCA risk factors to date. Some risk factors, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of this cancer. \nLay summary: Cholangiocarcinoma (CCA) is a cancer arising in the bile ducts inside (intrahepatic CCA) and connected to the liver (extrahepatic CCA). It is a very aggressive cancer: 95% of patients die within 5 years. CCA rates are increasing globally, but the causes of CCA are poorly understood. The few risk factors that are known account for only a minority of cases. In this study, we found that the strongest risk factors for both intrahepatic and extrahepatic CCA are cysts and stones in the bile ducts, cirrhosis, and hepatitis B and C viruses. Some risk factors for CCA, such as diabetes, although less strong, are increasing globally and may be contributing to rising rates of CCA. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"new proposal criteria future remnant liver volume older patients undergoing major hepatectomy biliary tract cancer objective evaluate whether advanced age increases risk severe complications major hepatectomy bile duct resection bdr patients biliary tract cancer establish new criteria percentage future remnant liver volume flv older patients undergoing operation background advanced age reported inhibit liver regeneration suppress immune function however little known risk aging high stress surgery biliary tract surgery methods consecutive patients underwent major hepatectomy bdr 2000 2013 retrospectively reviewed severe postoperative complications defined clavien dindo grade iv results 225 patients undergoing major hepatectomy bdr advanced age significantly correlated incidence severe postoperative complications cut value 69 years comparing postoperative complications incidences hyperbilirubinemia liver failure respiratory failure sepsis severe complications operation related death frequent older group moreover advanced age 69 years independent risk factor associated severe complications major hepatectomy bdr delayed liver regeneration reason age related risks incidence severe postoperative complications older patients significantly decreased flv set 45 conclusions advanced age strong independent risk factor severe complications major hepatectomy bdr decrease risk advanced age minimum limit flv operation set 45 patients aged 69 years pubmed","probabilities":0.9799733,"Title":"A New Proposal of Criteria for the Future Remnant Liver Volume in Older Patients Undergoing Major Hepatectomy for Biliary Tract Cancer","Abstract":"OBJECTIVE: To evaluate whether advanced age increases the risk of severe complications after major hepatectomy with bile duct resection (BDR) in patients with biliary tract cancer, and to establish new criteria for the percentage of the future remnant liver volume (%FLV) in older patients undergoing this operation. BACKGROUND: Advanced age is reported to inhibit liver regeneration and suppress immune function; however, little is known about the risk of aging in high-stress surgery, such as biliary tract surgery. METHODS: Consecutive patients who underwent major hepatectomy with BDR between 2000 and 2013 were retrospectively reviewed. Severe postoperative complications were defined as Clavien-Dindo grade ≥IV. RESULTS: In 225 patients undergoing major hepatectomy with BDR, advanced age was significantly correlated with the incidence of severe postoperative complications, with cut-off value of 69 years. In comparing postoperative complications, the incidences of hyperbilirubinemia, liver failure, respiratory failure, sepsis, severe complications, and operation-related death were more frequent in the older group. Moreover, advanced age (≥69 years) was an independent risk factor associated with severe complications after major hepatectomy with BDR. Delayed liver regeneration was the reason for the age-related risks. The incidence of severe postoperative complications in older patients was significantly decreased if %FLV was set at ≥45%. CONCLUSIONS: Advanced age is a strong independent risk factor for severe complications after major hepatectomy with BDR. To decrease the risk of advanced age, the minimum limit of %FLV for this operation should be set at ≥45% in patients aged ≥69 years.","Source":"PubMed","category":"HUMAN","training_data":"A New Proposal of Criteria for the Future Remnant Liver Volume in Older Patients Undergoing Major Hepatectomy for Biliary Tract Cancer OBJECTIVE: To evaluate whether advanced age increases the risk of severe complications after major hepatectomy with bile duct resection (BDR) in patients with biliary tract cancer, and to establish new criteria for the percentage of the future remnant liver volume (%FLV) in older patients undergoing this operation. BACKGROUND: Advanced age is reported to inhibit liver regeneration and suppress immune function; however, little is known about the risk of aging in high-stress surgery, such as biliary tract surgery. METHODS: Consecutive patients who underwent major hepatectomy with BDR between 2000 and 2013 were retrospectively reviewed. Severe postoperative complications were defined as Clavien-Dindo grade ≥IV. RESULTS: In 225 patients undergoing major hepatectomy with BDR, advanced age was significantly correlated with the incidence of severe postoperative complications, with cut-off value of 69 years. In comparing postoperative complications, the incidences of hyperbilirubinemia, liver failure, respiratory failure, sepsis, severe complications, and operation-related death were more frequent in the older group. Moreover, advanced age (≥69 years) was an independent risk factor associated with severe complications after major hepatectomy with BDR. Delayed liver regeneration was the reason for the age-related risks. The incidence of severe postoperative complications in older patients was significantly decreased if %FLV was set at ≥45%. CONCLUSIONS: Advanced age is a strong independent risk factor for severe complications after major hepatectomy with BDR. To decrease the risk of advanced age, the minimum limit of %FLV for this operation should be set at ≥45% in patients aged ≥69 years. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gemcitabine 1 versus gemcitabine cisplatin treatment patients advanced biliary tract cancer multicenter retrospective study objective study aimed compare safety efficacy combination therapy gemcitabine 1 gs versus gemcitabine cisplatin gc patients advanced biliary tract cancer btc methods multicenter retrospective cohort study total 212 patients advanced btc receiving gs n 125 gc n 87 july 2006 august 2015 analyzed primary endpoint overall survival os secondary endpoints progression free survival pfs objective tumor response safety results patient characteristics well balanced two groups except tumor size baseline sum largest diameter tumor 6 3 cm gs group vs 8 6 cm gc group p 0 01 although response rate higher gs group gc group 28 8 vs 10 3 p 0 01 median pfs os comparable two groups pfs 5 6 vs 7 6 months p 0 74 os 12 4 vs 9 2 months p 0 20 respectively stomatitis skin rash frequently observed gs group whereas anemia thrombocytopenia nausea renal toxicity commonly observed gc group conclusion study demonstrates gs gc similar regard safety efficacy patients advanced btc gs serve alternative treatment advanced btc first line chemotherapy pubmed","probabilities":0.9799733,"Title":"Gemcitabine and S-1 versus gemcitabine and cisplatin treatment in patients with advanced biliary tract cancer: a multicenter retrospective study","Abstract":"Objective This study aimed to compare the safety and efficacy of the combination therapy of gemcitabine and S-1 (GS) versus gemcitabine and cisplatin (GC) in patients with advanced biliary tract cancer (BTC). Methods In this multicenter retrospective cohort study, a total of 212 patients with advanced BTC receiving GS (n = 125) or GC (n = 87) between July 2006 and August 2015 were analyzed. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective tumor response, and safety. Results Patient characteristics were well balanced between the two groups, except for tumor size (the baseline sum of the largest diameter of the tumor: 6.3 cm in the GS group vs. 8.6 cm in the GC group, p = 0.01). Although the response rate was higher in the GS group than in the GC group (28.8% vs. 10.3%, p = 0.01), the median PFS and OS were comparable between the two groups (PFS of 5.6 vs. 7.6 months, p = 0.74; OS of 12.4 vs. 9.2 months, p = 0.20, respectively). Stomatitis and skin rash were more frequently observed in the GS group, whereas anemia, thrombocytopenia, nausea, and renal toxicity were more commonly observed in the GC group. Conclusion This study demonstrates that GS and GC are similar with regard to their safety and efficacy in patients with advanced BTC. GS could serve as an alternative treatment for advanced BTC as a first-line chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Gemcitabine and S-1 versus gemcitabine and cisplatin treatment in patients with advanced biliary tract cancer: a multicenter retrospective study Objective This study aimed to compare the safety and efficacy of the combination therapy of gemcitabine and S-1 (GS) versus gemcitabine and cisplatin (GC) in patients with advanced biliary tract cancer (BTC). Methods In this multicenter retrospective cohort study, a total of 212 patients with advanced BTC receiving GS (n = 125) or GC (n = 87) between July 2006 and August 2015 were analyzed. The primary endpoint was overall survival (OS). The secondary endpoints were progression-free survival (PFS), objective tumor response, and safety. Results Patient characteristics were well balanced between the two groups, except for tumor size (the baseline sum of the largest diameter of the tumor: 6.3 cm in the GS group vs. 8.6 cm in the GC group, p = 0.01). Although the response rate was higher in the GS group than in the GC group (28.8% vs. 10.3%, p = 0.01), the median PFS and OS were comparable between the two groups (PFS of 5.6 vs. 7.6 months, p = 0.74; OS of 12.4 vs. 9.2 months, p = 0.20, respectively). Stomatitis and skin rash were more frequently observed in the GS group, whereas anemia, thrombocytopenia, nausea, and renal toxicity were more commonly observed in the GC group. Conclusion This study demonstrates that GS and GC are similar with regard to their safety and efficacy in patients with advanced BTC. GS could serve as an alternative treatment for advanced BTC as a first-line chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"modifiable factors genetic predisposition associated gallbladder cancer concise review gallbladder cancer gbca frequent malignancy biliary tract also 6th common gastrointestinal tumor associated high lethality mainly due lack symptoms late thus incurable state many 80 patients diagnosed late stages disease allow palliative therapy result patients gbca die within 6 months diagnosis hence average 5 year survival exceed 5 currently surgical resection represents curative option gbca approach feasible early stage disease oncologic therapies limited use incidence gbca remarkably increased certain populations native north americans south indian females europe polish population clear date enhanced risk populations result common environmental exposure shared genetic risk factors review provide overview state art gbca research focus current knowledge concerning genetic environmental triggers tumor pubmed","probabilities":0.9799733,"Title":"Modifiable Factors and Genetic Predisposition Associated with Gallbladder Cancer A Concise Review","Abstract":"Gallbladder cancer (GbCa) is the most frequent malignancy of the biliary tract. It is also the 6th most common gastrointestinal tumor. It is associated with very high lethality, mainly due to the lack of symptoms up to a very late and thus incurable state. As many as 80% of patients are diagnosed at very late stages of disease, which allow only palliative therapy. As a result, most of the patients with GbCa will die within 6 months of the diagnosis, hence the average 5-year survival does not exceed 5%. Currently, surgical resection represents the only curative option in GbCa, but this approach is feasible only at an early stage of the disease. Other oncologic therapies are of limited use. The incidence of GbCa is remarkably increased in certain populations such as Native North Americans, South Indian females and, in Europe, in the Polish population. It is not clear to date if these enhanced risk populations are the result of common environmental exposure or of shared genetic risk factors. In this review we provide an overview of the state-of-art in GbCa research with the focus on the current knowledge concerning genetic and environmental triggers of this tumor.","Source":"PubMed","category":"HUMAN","training_data":"Modifiable Factors and Genetic Predisposition Associated with Gallbladder Cancer A Concise Review Gallbladder cancer (GbCa) is the most frequent malignancy of the biliary tract. It is also the 6th most common gastrointestinal tumor. It is associated with very high lethality, mainly due to the lack of symptoms up to a very late and thus incurable state. As many as 80% of patients are diagnosed at very late stages of disease, which allow only palliative therapy. As a result, most of the patients with GbCa will die within 6 months of the diagnosis, hence the average 5-year survival does not exceed 5%. Currently, surgical resection represents the only curative option in GbCa, but this approach is feasible only at an early stage of the disease. Other oncologic therapies are of limited use. The incidence of GbCa is remarkably increased in certain populations such as Native North Americans, South Indian females and, in Europe, in the Polish population. It is not clear to date if these enhanced risk populations are the result of common environmental exposure or of shared genetic risk factors. In this review we provide an overview of the state-of-art in GbCa research with the focus on the current knowledge concerning genetic and environmental triggers of this tumor. PubMed","prediction_labels":"HUMAN"},{"cleaned":"identification patients adjuvant therapy resection carcinoma extrahepatic bile ducts propensity score matched analysis background resectability rates extrahepatic cholangiocarcinoma increased time long term survival resection alone curative intent remains poor recent series suggest improved survival adjuvant therapy patient subsets benefiting adjuvant therapy clearly defined methods patients extrahepatic cholangiocarcinoma underwent resection curative intent received adjuvant therapy chemotherapy radiotherapy surgery alone sa identified u national cancer data base 2004 2014 cox regression identified covariates associated overall survival os adjuvant therapy sa cohorts matched 1 1 propensity scores based survival hazard cox modeling overall survival compared kaplan meier estimates results 4872 patients adjuvant chemotherapy used frequently 2416 49 6 often conjunction radiotherapy rt n 1555 64 4 adjuvant chemotherapy without rt used increasingly cases higher classification reference t1 2 t3 1 36 95 confidence interval ci 1 19 1 55 t4 1 77 95 ci 1 38 2 26 nodal positivity odds ratio 1 26 95 ci 1 01 1 56 lymphovascular invasion 1 21 95 ci 1 01 1 46 margin positive resection 1 85 95 ci 1 61 2 12 associated significant improvements os high risk subset propensity score matched cohort adjuvant therapy associated improved median os hilar tumors 40 0 vs 30 6 months p 0 025 distal tumors 33 0 vs 30 3 months p 0 123 chemoradiotherapy associated superior outcomes compared chemotherapy alone subset margin positive resection hazard ratio hr 0 63 95 ci 0 42 0 94 conclusions adjuvant multimodality therapy associated improved survival patients resected extrahepatic cholangiocarcinoma high risk features pubmed","probabilities":0.9799733,"Title":"Identification of Patients for Adjuvant Therapy After Resection of Carcinoma of the Extrahepatic Bile Ducts: A Propensity Score-Matched Analysis","Abstract":"BACKGROUND: Resectability rates for extrahepatic cholangiocarcinoma have increased over time, but long-term survival after resection alone with curative intent remains poor. Recent series suggest improved survival with adjuvant therapy. Patient subsets benefiting most from adjuvant therapy have not been clearly defined. METHODS: Patients with extrahepatic cholangiocarcinoma who underwent resection with curative intent and received adjuvant therapy (chemotherapy ± radiotherapy) or surgery alone (SA) were identified in the U.S. National Cancer Data Base (2004-2014). Cox regression identified covariates associated with overall survival (OS). Adjuvant therapy and SA cohorts were matched (1:1) by propensity scores based on the survival hazard in Cox modeling. Overall survival was compared by Kaplan-Meier estimates. RESULTS: Of 4872 patients, adjuvant chemotherapy was used frequently for 2416 (49.6%), often in conjunction with radiotherapy (RT) (n = 1555, 64.4%). Adjuvant chemotherapy with or without RT was used increasingly for cases with higher T classification [reference: T1-2; T3: 1.36; 95% confidence interval (CI), 1.19-1.55; T4: 1.77; 95% CI 1.38-2.26], nodal positivity [odds ratio (OR), 1.26; 95% CI 1.01-1.56], lymphovascular invasion (OR 1.21; 95% CI 1.01-1.46), or margin-positive resection (OR 1.85; 95% CI 1.61-2.12), and was associated with significant improvements in OS for each high-risk subset in the propensity score-matched cohort. Adjuvant therapy was associated with improved median OS for hilar tumors (40.0 vs 30.6 months; p = 0.025) but not distal tumors (33.0 vs 30.3 months; p = 0.123). Chemoradiotherapy was associated with superior outcomes compared with chemotherapy alone in the subset of margin-positive resection [hazard ratio (HR), 0.63; 95% CI 0.42-0.94]. CONCLUSIONS: Adjuvant multimodality therapy is associated with improved survival for patients with resected extrahepatic cholangiocarcinoma and high-risk features.","Source":"PubMed","category":"HUMAN","training_data":"Identification of Patients for Adjuvant Therapy After Resection of Carcinoma of the Extrahepatic Bile Ducts: A Propensity Score-Matched Analysis BACKGROUND: Resectability rates for extrahepatic cholangiocarcinoma have increased over time, but long-term survival after resection alone with curative intent remains poor. Recent series suggest improved survival with adjuvant therapy. Patient subsets benefiting most from adjuvant therapy have not been clearly defined. METHODS: Patients with extrahepatic cholangiocarcinoma who underwent resection with curative intent and received adjuvant therapy (chemotherapy ± radiotherapy) or surgery alone (SA) were identified in the U.S. National Cancer Data Base (2004-2014). Cox regression identified covariates associated with overall survival (OS). Adjuvant therapy and SA cohorts were matched (1:1) by propensity scores based on the survival hazard in Cox modeling. Overall survival was compared by Kaplan-Meier estimates. RESULTS: Of 4872 patients, adjuvant chemotherapy was used frequently for 2416 (49.6%), often in conjunction with radiotherapy (RT) (n = 1555, 64.4%). Adjuvant chemotherapy with or without RT was used increasingly for cases with higher T classification [reference: T1-2; T3: 1.36; 95% confidence interval (CI), 1.19-1.55; T4: 1.77; 95% CI 1.38-2.26], nodal positivity [odds ratio (OR), 1.26; 95% CI 1.01-1.56], lymphovascular invasion (OR 1.21; 95% CI 1.01-1.46), or margin-positive resection (OR 1.85; 95% CI 1.61-2.12), and was associated with significant improvements in OS for each high-risk subset in the propensity score-matched cohort. Adjuvant therapy was associated with improved median OS for hilar tumors (40.0 vs 30.6 months; p = 0.025) but not distal tumors (33.0 vs 30.3 months; p = 0.123). Chemoradiotherapy was associated with superior outcomes compared with chemotherapy alone in the subset of margin-positive resection [hazard ratio (HR), 0.63; 95% CI 0.42-0.94]. CONCLUSIONS: Adjuvant multimodality therapy is associated with improved survival for patients with resected extrahepatic cholangiocarcinoma and high-risk features. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical treatment gallbladder cancer systematic literature review objective evaluate existing evidence regarding surgical treatments gallbladder cancer health technology assessment specific aim evaluate whether extended surgery regarding liver lymph nodes bile duct adjacent organs compared cholecystectomy alone adult patient gallbladder cancer early late stages implies improved survival methods april 2015 updated june 2016 systematic literature search conducted pubmed embase cochrane library two authors independently screened titles abstracts full text articles certainty evidence evaluated according grade main results forty four observational studies non randomised controlled studies seven case series included radical resection including liver lymph node resection compared cholecystectomy alone showed significantly better survival patients stages t1b studies serious study limitations certainty evidence low grade survival benefit seen patients stage t1b higher lymph node resection evident stage t2 certainty evidence low grade uncertain whether routine bile duct resections improve overall survival patients gallbladder cancer stage t2 t4 grade conclusion data indicate prognosis improved liver resection lymph node resection performed patients tumour stage t1b higher evidence supporting resection bile duct adjacent organs necessary order achieve radicality pubmed","probabilities":0.9799733,"Title":"Surgical treatment for gallbladder cancer - a systematic literature review","Abstract":"OBJECTIVE: To evaluate existing evidence regarding surgical treatments for gallbladder cancer in a Health Technology Assessment. A specific aim was to evaluate whether extended surgery regarding liver, lymph nodes, bile duct, and adjacent organs compared with cholecystectomy alone in the adult patient with gallbladder cancer in early and late stages implies improved survival. METHODS: In April 2015 and updated in June 2016, a systematic literature search was conducted in PubMed, Embase, and the Cochrane Library. Two authors independently screened titles, abstracts, and full-text articles. The certainty of evidence was evaluated according to GRADE. MAIN RESULTS: Forty-four observational studies (non-randomised, controlled studies) and seven case series were included. Radical resection, including liver and lymph node resection, compared with cholecystectomy alone showed significantly better survival for patients with stages T1b and above. All studies had serious study limitations and the certainty of evidence was very low (GRADE ⊕○○○). A survival benefit seen in patients with stage T1b or higher with lymph node resection, was most evident in stage T2, but the certainty of evidence was low (GRADE ⊕⊕○○). It is uncertain whether routine bile duct resections improve overall survival in patients with gallbladder cancer stage T2-T4 (GRADE ⊕○○○). CONCLUSION: Data indicate that prognosis can be improved if liver resection and lymph node resection is performed in patients with tumour stage T1b or higher. There is no evidence supporting resection of the bile duct or adjacent organs if it is not necessary in order to achieve radicality.","Source":"PubMed","category":"HUMAN","training_data":"Surgical treatment for gallbladder cancer - a systematic literature review OBJECTIVE: To evaluate existing evidence regarding surgical treatments for gallbladder cancer in a Health Technology Assessment. A specific aim was to evaluate whether extended surgery regarding liver, lymph nodes, bile duct, and adjacent organs compared with cholecystectomy alone in the adult patient with gallbladder cancer in early and late stages implies improved survival. METHODS: In April 2015 and updated in June 2016, a systematic literature search was conducted in PubMed, Embase, and the Cochrane Library. Two authors independently screened titles, abstracts, and full-text articles. The certainty of evidence was evaluated according to GRADE. MAIN RESULTS: Forty-four observational studies (non-randomised, controlled studies) and seven case series were included. Radical resection, including liver and lymph node resection, compared with cholecystectomy alone showed significantly better survival for patients with stages T1b and above. All studies had serious study limitations and the certainty of evidence was very low (GRADE ⊕○○○). A survival benefit seen in patients with stage T1b or higher with lymph node resection, was most evident in stage T2, but the certainty of evidence was low (GRADE ⊕⊕○○). It is uncertain whether routine bile duct resections improve overall survival in patients with gallbladder cancer stage T2-T4 (GRADE ⊕○○○). CONCLUSION: Data indicate that prognosis can be improved if liver resection and lymph node resection is performed in patients with tumour stage T1b or higher. There is no evidence supporting resection of the bile duct or adjacent organs if it is not necessary in order to achieve radicality. PubMed","prediction_labels":"HUMAN"},{"cleaned":"shox2 sept9 methylation potential biomarker diagnosis biliary tract cancer background biliary tract carcinoma btc fatal malignancy late clinical presentation novel molecular markers early diagnosis urgently needed purpose study evaluate diagnostic prognostic value promoter hypermethylation shox2 sept9 btc methods relative dna methylation shox2 sept9 quantified tumor specimens matched normal adjacent tissue nat 71 btc patients well plasma samples independent prospective cohort 20 cholangiocarcinoma patients 100 control patients receiver operating characteristic roc curve analyses performed probe diagnostic ability methylation markers dna methylation correlated clinicopathological survival data results shox2 methylation significantly higher tumor tissue nat p 0 001 correctly identified 71 btc specimens 100 specificity auc 0 918 95 ci 0 865 0 971 elevated dna methylation levels also found plasma derived cholangiocarcinoma patients shox2 sept9 methylation marker panel achieved sensitivity 45 specificity 99 differentiating samples patients without cholangiocarcinoma auc 0 752 95 ci 0 631 0 873 conclusion shox2 sept9 frequently methylated biliary tract cancers promoter hypermethylation shox2 sept9 may therefore serve biomarker supporting diagnosis finding therapy monitoring clinical specimens google scholar","probabilities":0.875,"Title":"Shox2 And Sept9 Methylation Is A Potential Biomarker For The Diagnosis Of Biliary Tract Cancer","Abstract":"Background: Biliary tract carcinoma (BTC) is a fatal malignancy with a late clinical presentation. Novel molecular markers for early diagnosis are urgently needed. The purpose of this study was to evaluate the diagnostic and prognostic value of promoter hypermethylation of SHOX2 and SEPT9 in BTC.\nMethods: Relative DNA methylation of SHOX2 and SEPT9 was quantified in tumor specimens and matched normal adjacent tissue (NAT) from 71 BTC patients, as well as in plasma samples from an independent prospective cohort of 20 cholangiocarcinoma patients and 100 control patients. Receiver operating characteristic (ROC) curve analyses were performed to probe the diagnostic ability of both methylation markers. DNA methylation was correlated to clinicopathological and survival data.\nResults: SHOX2 methylation was significantly higher in tumor tissue than in NAT (p < 0.001) and correctly identified 71% of BTC specimens with 100% specificity (AUC = 0.918; 95% CI 0.865-0.971). Elevated DNA methylation levels were also found in plasma derived from cholangiocarcinoma patients. SHOX2 and SEPT9 methylation as a marker panel achieved a sensitivity of 45% and a specificity of 99% in differentiating between samples from patients with and without cholangiocarcinoma (AUC = 0.752; 95% CI 0.631-0.873).\nConclusion: SHOX2 and SEPT9 are frequently methylated in biliary tract cancers. Promoter hypermethylation of SHOX2 and SEPT9 may therefore serve as a biomarker supporting diagnosis finding and therapy monitoring in clinical specimens.","Source":"Google Scholar","category":"ANIMAL","training_data":"Shox2 And Sept9 Methylation Is A Potential Biomarker For The Diagnosis Of Biliary Tract Cancer Background: Biliary tract carcinoma (BTC) is a fatal malignancy with a late clinical presentation. Novel molecular markers for early diagnosis are urgently needed. The purpose of this study was to evaluate the diagnostic and prognostic value of promoter hypermethylation of SHOX2 and SEPT9 in BTC.\nMethods: Relative DNA methylation of SHOX2 and SEPT9 was quantified in tumor specimens and matched normal adjacent tissue (NAT) from 71 BTC patients, as well as in plasma samples from an independent prospective cohort of 20 cholangiocarcinoma patients and 100 control patients. Receiver operating characteristic (ROC) curve analyses were performed to probe the diagnostic ability of both methylation markers. DNA methylation was correlated to clinicopathological and survival data.\nResults: SHOX2 methylation was significantly higher in tumor tissue than in NAT (p < 0.001) and correctly identified 71% of BTC specimens with 100% specificity (AUC = 0.918; 95% CI 0.865-0.971). Elevated DNA methylation levels were also found in plasma derived from cholangiocarcinoma patients. SHOX2 and SEPT9 methylation as a marker panel achieved a sensitivity of 45% and a specificity of 99% in differentiating between samples from patients with and without cholangiocarcinoma (AUC = 0.752; 95% CI 0.631-0.873).\nConclusion: SHOX2 and SEPT9 are frequently methylated in biliary tract cancers. Promoter hypermethylation of SHOX2 and SEPT9 may therefore serve as a biomarker supporting diagnosis finding and therapy monitoring in clinical specimens. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"expression clinicopathological significance antiapoptotis protein survivin gallbladder cancer background clinical significance survivin antiapoptosis protein gallbladder cancer yet established aims study performed assess expression pattern survivin benign malignant gallbladder lesions using immunohistochemistry ihc assess clinicopathological significance settings design prospective study july 2012 july 2014 performed part intramural research project materials methods tissue samples resected gallbladder cholelithiasis n 27 carcinoma gallbladder n 24 evaluated survivin expression ihc using scoring system expression correlated different clinicopathological parameters statistical analysis fisher exact test student test chi square test used appropriate data analysis kaplan meier methods used calculate overall disease free survival rates among different groups two sided p 0 05 considered significant results benign group 19 females age mean standard deviation sd 45 14 years malignant group 20 females age mean sd 48 9 13 4 years comparable respect menopausal status presence size types stones however survivin expression significantly higher 66 7 95 confidence interval ci 24 75 gallbladder cancer cholelithiasis group 33 ci 46 83 p 0 025 expression correlate gender age menopausal status presence gallstones size number type tumor differentiation tumor stage conclusions significantly higher expression survivin protein gallbladder cancer compared cholelithiasis group suggests role gallbladder carcinogenesis though may prognostic value pubmed","probabilities":0.7966102,"Title":"Expression and clinicopathological significance of antiapoptotis protein survivin in gallbladder cancer","Abstract":"BACKGROUND: Clinical significance of survivin (antiapoptosis protein) in gallbladder cancer is not yet established. AIMS: This study was performed to assess the expression pattern of survivin in benign and malignant gallbladder lesions using immunohistochemistry (IHC), and to assess its clinicopathological significance. SETTINGS AND DESIGN: Prospective study from July 2012 to July 2014 was performed as a part of intramural research project. MATERIALS AND METHODS: Tissue samples from resected gallbladder for cholelithiasis (n = 27) and carcinoma gallbladder (n= 24) were evaluated for survivin expression by IHC using a scoring system. Their expression was correlated with different clinicopathological parameters. STATISTICAL ANALYSIS: Fisher's exact test, Student's t-test, and Chi-square test were used as appropriate for data analysis. Kaplan-Meier methods were used to calculate overall and disease-free survival rates among different groups. Two-sided P< 0.05 was considered as significant. RESULTS: Benign group (19 females, age [mean ± standard deviation [SD] 45 ± 14 years) and malignant group (20 females, age [mean ± SD] 48.9 ± 13.4 years) were comparable with respect to menopausal status, presence, size and types of stones. However, survivin expression was significantly higher (66.7%, 95% confidence interval [CI] 24-75) in gallbladder cancer than in cholelithiasis group (33%, CI 46-83), P= 0.025). Its expression did not correlate with gender, age, menopausal status, presence of gallstones or their size, number and type, tumor differentiation, and tumor stage. CONCLUSIONS: Significantly higher expression of survivin protein in gallbladder cancer as compared to cholelithiasis group suggests its role in gallbladder carcinogenesis though it may not have prognostic value.","Source":"PubMed","category":"HUMAN","training_data":"Expression and clinicopathological significance of antiapoptotis protein survivin in gallbladder cancer BACKGROUND: Clinical significance of survivin (antiapoptosis protein) in gallbladder cancer is not yet established. AIMS: This study was performed to assess the expression pattern of survivin in benign and malignant gallbladder lesions using immunohistochemistry (IHC), and to assess its clinicopathological significance. SETTINGS AND DESIGN: Prospective study from July 2012 to July 2014 was performed as a part of intramural research project. MATERIALS AND METHODS: Tissue samples from resected gallbladder for cholelithiasis (n = 27) and carcinoma gallbladder (n= 24) were evaluated for survivin expression by IHC using a scoring system. Their expression was correlated with different clinicopathological parameters. STATISTICAL ANALYSIS: Fisher's exact test, Student's t-test, and Chi-square test were used as appropriate for data analysis. Kaplan-Meier methods were used to calculate overall and disease-free survival rates among different groups. Two-sided P< 0.05 was considered as significant. RESULTS: Benign group (19 females, age [mean ± standard deviation [SD] 45 ± 14 years) and malignant group (20 females, age [mean ± SD] 48.9 ± 13.4 years) were comparable with respect to menopausal status, presence, size and types of stones. However, survivin expression was significantly higher (66.7%, 95% confidence interval [CI] 24-75) in gallbladder cancer than in cholelithiasis group (33%, CI 46-83), P= 0.025). Its expression did not correlate with gender, age, menopausal status, presence of gallstones or their size, number and type, tumor differentiation, and tumor stage. CONCLUSIONS: Significantly higher expression of survivin protein in gallbladder cancer as compared to cholelithiasis group suggests its role in gallbladder carcinogenesis though it may not have prognostic value. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatic arterial infusion unresectable intrahepatic cholangiocarcinoma update survival two prospective clinical trials background patients unresectable intrahepatic cholangiocarcinoma icc treatment options limited survival poor study summarizes long term outcome two previously reported clinical trials using hepatic arterial infusion hai floxuridine dexamethasone without bevacizumab advanced icc methods prospectively collected clinicopathologic survival data retrospectively reviewed response based response evaluation criteria solid tumors recist pre hai dynamic contrast enhanced magnetic resonance imaging dce mri images reviewed tumor perfusion data correlated outcome results forty four patients analyzed floxuridine 26 floxuridine bevacizumab 18 median follow 29 3 months 41 patients died disease partial response recist observed 48 50 stable disease three patients underwent resection response 82 received additional hai removal trials median survival similar trials floxuridine 29 3 months vs floxuridine bevacizumab 28 5 months p 0 96 ten 23 patients survived 3 years including 5 11 survived 5 years tumor perfusion measured pre treatment dce mri area gadolinium concentration curve 90 180 auc90 auc180 respectively significantly higher 3 year survivors factor distinguished group 3 year survivors mean auc90 22 6 vs 15 9 mm p 0 025 mean auc180 48 9 vs 32 3 mm p 0 003 respectively median hepatic progression free survival longer 3 year survivors 12 9 vs 9 3 months respectively p 0 008 conclusions hai chemotherapy result prolonged survival unresectable icc pre hai dce mri may predict treatment outcome stn","probabilities":0.9799733,"Title":"Hepatic Arterial Infusion For Unresectable Intrahepatic Cholangiocarcinoma: An Update On Survival From Two Prospective Clinical Trials","Abstract":"Background: For patients with unresectable intrahepatic cholangiocarcinoma (ICC), treatment options are limited and survival is poor. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine and dexamethasone (with or without bevacizumab) in advanced ICC. \r\n\r\n Methods: Prospectively collected clinicopathologic and survival data were retrospectively reviewed. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion data correlated with outcome. \r\n\r\n Results: Forty-four patients were analyzed (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3 months, 41 patients had died of disease. Partial response by RECIST was observed in 48 %, and 50 % had stable disease. Three patients underwent resection after response, and 82 % received additional HAI after removal from the trials. Median survival was similar in both trials (floxuridine 29.3 months vs. floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived ≥3 years, including 5 (11 %) who survived ≥5 years. Tumor perfusion measured on pre-treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s (AUC90 and AUC180, respectively)] was significantly higher in ≥3-year survivors and was the only factor that distinguished this group from <3-year survivors (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p = 0.003, respectively). Median hepatic progression-free survival was longer in ≥3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008). \r\n\r\n Conclusions: HAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI DCE-MRI may predict treatment outcome.","Source":"STN","category":"HUMAN","training_data":"Hepatic Arterial Infusion For Unresectable Intrahepatic Cholangiocarcinoma: An Update On Survival From Two Prospective Clinical Trials Background: For patients with unresectable intrahepatic cholangiocarcinoma (ICC), treatment options are limited and survival is poor. This study summarizes the long-term outcome of two previously reported clinical trials using hepatic arterial infusion (HAI) with floxuridine and dexamethasone (with or without bevacizumab) in advanced ICC. \r\n\r\n Methods: Prospectively collected clinicopathologic and survival data were retrospectively reviewed. Response was based on Response Evaluation Criteria in Solid Tumors (RECIST). Pre-HAI dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) images were reviewed, and tumor perfusion data correlated with outcome. \r\n\r\n Results: Forty-four patients were analyzed (floxuridine, 26; floxuridine/bevacizumab, 18). At a median follow-up of 29.3 months, 41 patients had died of disease. Partial response by RECIST was observed in 48 %, and 50 % had stable disease. Three patients underwent resection after response, and 82 % received additional HAI after removal from the trials. Median survival was similar in both trials (floxuridine 29.3 months vs. floxuridine/bevacizumab 28.5 months; p = 0.96). Ten (23 %) patients survived ≥3 years, including 5 (11 %) who survived ≥5 years. Tumor perfusion measured on pre-treatment DCE-MRI [area under the gadolinium concentration curve at 90 and 180 s (AUC90 and AUC180, respectively)] was significantly higher in ≥3-year survivors and was the only factor that distinguished this group from <3-year survivors (mean AUC90 22.6 vs. 15.9 mM s, p = 0.025, and mean AUC180 48.9 vs. 32.3 mM s, p = 0.003, respectively). Median hepatic progression-free survival was longer in ≥3-year survivors (12.9 vs. 9.3 months, respectively; p = 0.008). \r\n\r\n Conclusions: HAI chemotherapy can result in prolonged survival in unresectable ICC. Pre-HAI DCE-MRI may predict treatment outcome. STN","prediction_labels":"HUMAN"},{"cleaned":"retrospective study 1 monotherapy second line treatment patients advanced biliary tract cancer objective gemcitabine widely used cisplatin plus gemcitabine considered standard first line chemotherapy patients advanced biliary tract cancer however standard therapy established following progression gemcitabine containing first line therapy 1 monotherapy second line chemotherapy still well known practical setting study aimed clarify efficacy safety methods retrospectively reviewed 55 consecutive patients received 1 monotherapy second line chemotherapy failure gemcitabine containing regimen institution september 2007 march 2011 inclusion criteria preserved organ function eastern cooperative oncology group performance status 0 2 without massive ascites pleural effusion 1 administered orally twice day dose 40 mg m 2 28 days followed 14 days rest results fifty one patients selected analysis overall response rate 4 0 disease control rate 38 0 median survival time 6 0 months median progression free survival 2 3 months adverse events generally mild treatment related death occur subgroup analysis overall survival significantly shorter patients peritoneal dissemination shown response first line chemotherapy p 0 033 0 023 respectively conclusions 1 monotherapy second line chemotherapy patients gemcitabine refractory advanced biliary tract cancer also feasible practical setting efficacy almost previous prospective study pubmed","probabilities":0.9799733,"Title":"A retrospective study of S-1 monotherapy as second-line treatment for patients with advanced biliary tract cancer","Abstract":"OBJECTIVE: Gemcitabine has been widely used, and cisplatin plus gemcitabine is considered as standard first-line chemotherapy for patients with advanced biliary tract cancer. However, no standard therapy was established following the progression to gemcitabine-containing first-line therapy. As S-1 monotherapy as second-line chemotherapy is still not well known in a practical setting this study aimed to clarify its efficacy and safety. METHODS: We retrospectively reviewed 55 consecutive patients who received S-1 monotherapy as second-line chemotherapy after failure of a gemcitabine-containing regimen at our institution from September 2007 to March 2011. The inclusion criteria were preserved organ function and an Eastern Cooperative Oncology Group performance status of 0-2 and without massive ascites or pleural effusion. S-1 was administered orally twice a day at a dose of 40 mg/m(2) for 28 days, followed by 14 days of rest. RESULTS: Fifty-one patients were selected for this analysis. The overall response rate was 4.0% and the disease control rate was 38.0%. The median survival time was 6.0 months and the median progression-free survival was 2.3 months. Adverse events were generally mild, and treatment-related death did not occur. In the subgroup analysis, overall survival was significantly shorter in the patients with peritoneal dissemination and those who had shown no response to the first-line chemotherapy (P= 0.033 and 0.023, respectively). CONCLUSIONS: S-1 monotherapy as the second-line chemotherapy for patients with gemcitabine-refractory advanced biliary tract cancer is also feasible in a practical setting and its efficacy is almost the same as in the previous prospective study.","Source":"PubMed","category":"HUMAN","training_data":"A retrospective study of S-1 monotherapy as second-line treatment for patients with advanced biliary tract cancer OBJECTIVE: Gemcitabine has been widely used, and cisplatin plus gemcitabine is considered as standard first-line chemotherapy for patients with advanced biliary tract cancer. However, no standard therapy was established following the progression to gemcitabine-containing first-line therapy. As S-1 monotherapy as second-line chemotherapy is still not well known in a practical setting this study aimed to clarify its efficacy and safety. METHODS: We retrospectively reviewed 55 consecutive patients who received S-1 monotherapy as second-line chemotherapy after failure of a gemcitabine-containing regimen at our institution from September 2007 to March 2011. The inclusion criteria were preserved organ function and an Eastern Cooperative Oncology Group performance status of 0-2 and without massive ascites or pleural effusion. S-1 was administered orally twice a day at a dose of 40 mg/m(2) for 28 days, followed by 14 days of rest. RESULTS: Fifty-one patients were selected for this analysis. The overall response rate was 4.0% and the disease control rate was 38.0%. The median survival time was 6.0 months and the median progression-free survival was 2.3 months. Adverse events were generally mild, and treatment-related death did not occur. In the subgroup analysis, overall survival was significantly shorter in the patients with peritoneal dissemination and those who had shown no response to the first-line chemotherapy (P= 0.033 and 0.023, respectively). CONCLUSIONS: S-1 monotherapy as the second-line chemotherapy for patients with gemcitabine-refractory advanced biliary tract cancer is also feasible in a practical setting and its efficacy is almost the same as in the previous prospective study. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact neutrophil lymphocyte ratio platelet lymphocyte ratio among patients intrahepatic cholangiocarcinoma background neutrophil lymphocyte ratio platelets lymphocyte ratio may host factors associated prognosis sought determine whether neutrophil lymphocyte platelets lymphocyte ratio associated overall survival among patients undergoing surgery intrahepatic cholangiocarcinoma methods patients underwent resection intrahepatic cholangiocarcinoma 1990 2015 identified 12 major centers clinicopathologic factors overall survival compared among patients stratified neutrophil lymphocyte ratio platelets lymphocyte ratio risk factors identified multivariable analysis included prognostic model discrimination assessed using harrell concordance index c index results total 991 patients identified median neutrophil lymphocyte ratio platelets lymphocyte ratio 2 7 interquartile range iqr 2 0 4 0 109 6 iqr 72 4 158 8 respectively preoperative neutrophil lymphocyte ratio elevated 5 100 patients 10 0 preoperative platelets lymphocyte ratio 190 94 patients 15 2 patients low high neutrophil lymphocyte ratio platelets lymphocyte ratio generally similar baseline characteristics regard tumor characteristics overall survival 37 7 months 95 confidence interval ci 32 7 42 6 1 3 5 year overall survival 78 8 51 6 39 3 respectively patients neutrophil lymphocyte ratio 5 median survival 47 1 months 95 ci 37 9 53 3 compared median survival 21 9 months 95 ci 4 8 39 1 among patients neutrophil lymphocyte ratio 5 p 001 contrast patients platelets lymphocyte ratio 190 vs platelets lymphocyte ratio 190 comparable long term survival p 05 multivariable analysis elevated neutrophil lymphocyte ratio independently associated decreased overall survival hazard ratio 1 04 95 ci 1 01 1 07 p 002 patients stratified low versus high risk groups based standard tumor specific factors lymph node status tumor size number vascular invasion c index 0 62 neutrophil lymphocyte ratio added prognostic model discriminatory ability model improved c index 0 71 conclusion elevated neutrophil lymphocyte ratio independently associated worse overall survival improved prognostic estimation long term survival among patients intrahepatic cholangiocarcinoma undergoing resection pubmed","probabilities":0.9799733,"Title":"The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio may be host factors associated with prognosis. We sought to determine whether neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio were associated with overall survival among patients undergoing surgery for intrahepatic cholangiocarcinoma. METHODS: Patients who underwent resection for intrahepatic cholangiocarcinoma between 1990 and 2015 were identified from 12 major centers. Clinicopathologic factors and overall survival were compared among patients stratified by neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio. Risk factors identified on multivariable analysis were included in a prognostic model and the discrimination was assessed using Harrell's concordance index (C index). RESULTS: A total of 991 patients were identified. Median neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio were 2.7 (interquartile range [IQR]: 2.0-4.0) and 109.6 (IQR: 72.4-158.8), respectively. Preoperative neutrophil-to-lymphocyte ratio was elevated (≥5) in 100 patients (10.0%) and preoperative platelets-to-lymphocyte ratio (≥190) in 94 patients (15.2%). Patients with low and high neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio generally had similar baseline characteristics with regard to tumor characteristics. Overall survival was 37.7 months (95% confidence interval [CI]: 32.7-42.6); 1-, 3-, and 5-year overall survival was 78.8%, 51.6%, and 39.3%, respectively. Patients with an neutrophil-to-lymphocyte ratio <5 had a median survival of 47.1 months (95% CI: 37.9-53.3) compared with a median survival of 21.9 months (95% CI: 4.8-39.1) among patients with an neutrophil-to-lymphocyte ratio ≥5 (P = .001). In contrast, patients who had a platelets-to-lymphocyte ratio <190 vs platelets-to-lymphocyte ratio ≥190 had comparable long-term survival (P > .05). On multivariable analysis, an elevated neutrophil-to-lymphocyte ratio was independently associated with decreased overall survival (hazard ratio: 1.04, 95% CI: 1.01-1.07; P = .002). Patients could be stratified into low- versus high-risk groups based on standard tumor-specific factors such as lymph node status, tumor size, number, and vascular invasion (C index 0.62). When neutrophil-to-lymphocyte ratio was added to the prognostic model, the discriminatory ability of the model improved (C index 0.71). CONCLUSION: Elevated neutrophil-to-lymphocyte ratio was independently associated with worse overall survival and improved the prognostic estimation of long-term survival among patients with intrahepatic cholangiocarcinoma undergoing resection.","Source":"PubMed","category":"HUMAN","training_data":"The impact of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio among patients with intrahepatic cholangiocarcinoma BACKGROUND: Neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio may be host factors associated with prognosis. We sought to determine whether neutrophil-to-lymphocyte and platelets-to-lymphocyte ratio were associated with overall survival among patients undergoing surgery for intrahepatic cholangiocarcinoma. METHODS: Patients who underwent resection for intrahepatic cholangiocarcinoma between 1990 and 2015 were identified from 12 major centers. Clinicopathologic factors and overall survival were compared among patients stratified by neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio. Risk factors identified on multivariable analysis were included in a prognostic model and the discrimination was assessed using Harrell's concordance index (C index). RESULTS: A total of 991 patients were identified. Median neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio were 2.7 (interquartile range [IQR]: 2.0-4.0) and 109.6 (IQR: 72.4-158.8), respectively. Preoperative neutrophil-to-lymphocyte ratio was elevated (≥5) in 100 patients (10.0%) and preoperative platelets-to-lymphocyte ratio (≥190) in 94 patients (15.2%). Patients with low and high neutrophil-to-lymphocyte ratio and platelets-to-lymphocyte ratio generally had similar baseline characteristics with regard to tumor characteristics. Overall survival was 37.7 months (95% confidence interval [CI]: 32.7-42.6); 1-, 3-, and 5-year overall survival was 78.8%, 51.6%, and 39.3%, respectively. Patients with an neutrophil-to-lymphocyte ratio <5 had a median survival of 47.1 months (95% CI: 37.9-53.3) compared with a median survival of 21.9 months (95% CI: 4.8-39.1) among patients with an neutrophil-to-lymphocyte ratio ≥5 (P = .001). In contrast, patients who had a platelets-to-lymphocyte ratio <190 vs platelets-to-lymphocyte ratio ≥190 had comparable long-term survival (P > .05). On multivariable analysis, an elevated neutrophil-to-lymphocyte ratio was independently associated with decreased overall survival (hazard ratio: 1.04, 95% CI: 1.01-1.07; P = .002). Patients could be stratified into low- versus high-risk groups based on standard tumor-specific factors such as lymph node status, tumor size, number, and vascular invasion (C index 0.62). When neutrophil-to-lymphocyte ratio was added to the prognostic model, the discriminatory ability of the model improved (C index 0.71). CONCLUSION: Elevated neutrophil-to-lymphocyte ratio was independently associated with worse overall survival and improved the prognostic estimation of long-term survival among patients with intrahepatic cholangiocarcinoma undergoing resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"dysfunction subtelomeric methylation telomere length different grades gallbladder cancer background telomeres play important role cancer progression recently shown subtelomeric methylation negatively regulates telomere length various diseases including cancers evaluated influence subtelomeric methylation telomere dysfunction gallbladder cancer gbc whether dysfunction affected presence gallstones methods relative telomere length subtelomeric methylation levels assessed using monochrome multiplex quantitative polymerase chain reaction bisulfite sequencing respectively different gallbladder tissue types including different grades gbc gallstones adjacent non tumor results found telomere length shorten significantly overall gbc specifically early grade cancer also found d4z4 dnf92 subtelomeric sequences hypermethylated hypomethylated respectively gbc however methylation levels differed significantly early grade cancer find specific correlation subtelomeric methylation telomere length gbc interestingly telomere length subtelomeric methylation differed significantly gbc without gallstones gbc gallstones conclusions study thus suggests telomere dysfunction changes methylation levels may occur earlier progression gbc presence gallstones may influence telomere length well methylation levels stn","probabilities":0.7966102,"Title":"Dysfunction Of Subtelomeric Methylation And Telomere Length In Different Grades Of Gallbladder Cancer","Abstract":"Background: Telomeres play an important role in cancer progression. Recently it has been shown that subtelomeric methylation negatively regulates telomere length in various diseases, including cancers. Here, we evaluated the influence of subtelomeric methylation in telomere dysfunction in gallbladder cancer (GBC), and whether this dysfunction is affected by the presence of gallstones. \r\n\r\n Methods: Relative telomere length and subtelomeric methylation levels were assessed using monochrome multiplex quantitative polymerase chain reaction and bisulfite sequencing, respectively, in different gallbladder tissue types including different grades of GBC, gallstones and adjacent non-tumor. \r\n\r\n Results: We found telomere length to shorten significantly in overall GBC, but specifically in early grade cancer. We also found D4Z4 and DNF92 subtelomeric sequences to be hypermethylated and hypomethylated, respectively, in GBC; however, their methylation levels differed significantly, only in early grade cancer. We could not find any specific correlation between subtelomeric methylation and telomere length in GBC. Interestingly, telomere length and subtelomeric methylation differed significantly in GBC without gallstones but not in GBC with gallstones. \r\n\r\n Conclusions: This study, thus, suggests that telomere dysfunction and changes in methylation levels may occur earlier in the progression of GBC, while the presence of gallstones may have no influence on telomere length as well as on methylation levels.","Source":"STN","category":"ANIMAL","training_data":"Dysfunction Of Subtelomeric Methylation And Telomere Length In Different Grades Of Gallbladder Cancer Background: Telomeres play an important role in cancer progression. Recently it has been shown that subtelomeric methylation negatively regulates telomere length in various diseases, including cancers. Here, we evaluated the influence of subtelomeric methylation in telomere dysfunction in gallbladder cancer (GBC), and whether this dysfunction is affected by the presence of gallstones. \r\n\r\n Methods: Relative telomere length and subtelomeric methylation levels were assessed using monochrome multiplex quantitative polymerase chain reaction and bisulfite sequencing, respectively, in different gallbladder tissue types including different grades of GBC, gallstones and adjacent non-tumor. \r\n\r\n Results: We found telomere length to shorten significantly in overall GBC, but specifically in early grade cancer. We also found D4Z4 and DNF92 subtelomeric sequences to be hypermethylated and hypomethylated, respectively, in GBC; however, their methylation levels differed significantly, only in early grade cancer. We could not find any specific correlation between subtelomeric methylation and telomere length in GBC. Interestingly, telomere length and subtelomeric methylation differed significantly in GBC without gallstones but not in GBC with gallstones. \r\n\r\n Conclusions: This study, thus, suggests that telomere dysfunction and changes in methylation levels may occur earlier in the progression of GBC, while the presence of gallstones may have no influence on telomere length as well as on methylation levels. STN","prediction_labels":"HUMAN"},{"cleaned":"retrospective study ampullary adenocarcinomas overall survival responsiveness fluoropyrimidine based chemotherapy background whether carcinomas ampulla vater classified biliary tract tumors treated similar manner remains unknown sought compare outcomes similarly staged periampullary adenocarcinomas aas analyze chemotherapy responsiveness aas patients methods total 905 patients resected periampullary adenocarcinomas identified prospective surgical registry 1988 2010 second cohort 64 metastatic aa patients 1992 2009 received either front line fluoropyrimidine based gemcitabine based chemotherapy also identified results overall survival os aas similar survival duodenal adenocarcinomas significantly different extrahepatic biliary pancreatic adenocarcinomas p 0 001 comparison multivariate analysis aas significantly improved os comparison extrahepatic biliary adenocarcinomas hr 1 97 p 0 006 fluoropyrimidine based opposed gemcitabine based chemotherapy metastatic aas resulted significant improvement time progression p 0 001 trend toward benefit os p 0 07 multivariate analysis conclusions differences natural history ampullary extrahepatic biliary adenocarcinomas exist analyses metastatic ampullary adenocarcinomas suggest fluoropyrimidine based chemotherapy may represent appropriate front line chemotherapy approach pubmed","probabilities":0.9799733,"Title":"A retrospective study of ampullary adenocarcinomas: overall survival and responsiveness to fluoropyrimidine-based chemotherapy","Abstract":"BACKGROUND: Whether carcinomas of the ampulla of Vater should be classified with biliary tract tumors and treated in a similar manner remains unknown. We sought to compare the outcomes of similarly staged periampullary adenocarcinomas (AAs) and analyze the chemotherapy responsiveness of AAs. PATIENTS AND METHODS: A total of 905 patients with resected periampullary adenocarcinomas were identified from a prospective surgical registry from 1988 to 2010. A second cohort of 64 metastatic AA patients from 1992 to 2009 who received either front-line fluoropyrimidine-based or gemcitabine-based chemotherapy was also identified. RESULTS: Overall survival (OS) for AAs was similar to survival with duodenal adenocarcinomas, but was significantly different from both extrahepatic biliary and pancreatic adenocarcinomas (P < 0.001 for each comparison). In multivariate analysis, AAs had a significantly improved OS in comparison with extrahepatic biliary adenocarcinomas (HR = 1.97, P = 0.006). Fluoropyrimidine-based as opposed to gemcitabine-based chemotherapy for metastatic AAs resulted in a significant improvement in time to progression (P = 0.001) but only a trend toward benefit for OS (P = 0.07) in multivariate analysis. CONCLUSIONS: Differences in the natural history of ampullary and extrahepatic biliary adenocarcinomas exist. Analyses of metastatic ampullary adenocarcinomas suggest that fluoropyrimidine-based chemotherapy may represent a more appropriate front-line chemotherapy approach.","Source":"PubMed","category":"HUMAN","training_data":"A retrospective study of ampullary adenocarcinomas: overall survival and responsiveness to fluoropyrimidine-based chemotherapy BACKGROUND: Whether carcinomas of the ampulla of Vater should be classified with biliary tract tumors and treated in a similar manner remains unknown. We sought to compare the outcomes of similarly staged periampullary adenocarcinomas (AAs) and analyze the chemotherapy responsiveness of AAs. PATIENTS AND METHODS: A total of 905 patients with resected periampullary adenocarcinomas were identified from a prospective surgical registry from 1988 to 2010. A second cohort of 64 metastatic AA patients from 1992 to 2009 who received either front-line fluoropyrimidine-based or gemcitabine-based chemotherapy was also identified. RESULTS: Overall survival (OS) for AAs was similar to survival with duodenal adenocarcinomas, but was significantly different from both extrahepatic biliary and pancreatic adenocarcinomas (P < 0.001 for each comparison). In multivariate analysis, AAs had a significantly improved OS in comparison with extrahepatic biliary adenocarcinomas (HR = 1.97, P = 0.006). Fluoropyrimidine-based as opposed to gemcitabine-based chemotherapy for metastatic AAs resulted in a significant improvement in time to progression (P = 0.001) but only a trend toward benefit for OS (P = 0.07) in multivariate analysis. CONCLUSIONS: Differences in the natural history of ampullary and extrahepatic biliary adenocarcinomas exist. Analyses of metastatic ampullary adenocarcinomas suggest that fluoropyrimidine-based chemotherapy may represent a more appropriate front-line chemotherapy approach. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental non benign gallbladder histopathology routine cholecystectomy uk population aim analyse range histopathology detected largest published united kingdom series cholecystectomy specimens evaluate rational selective histopathological analysis methods incidental gallbladder malignancy rare united kingdom recent literature supporting selective histological assessment gallbladders routine cholecystectomy cholecystectomy gallbladder specimens examined histopathology department hospital five year period march 2008 march 2013 retrospectively analysed data collected specimens demonstrating carcinoma dysplasia polypoid growths results study included 4027 patients majority 97 specimens exhibited gallstone cholecystitis related disease polyps demonstrated 44 1 09 majority cholesterol based 41 44 dysplasia ranging low multifocal high grade demonstrated 55 1 37 incidental primary gallbladder adenocarcinoma detected 6 specimens 0 15 5 female 1 male single gallbladder revealed carcinoma situ 0 02 large single centre study demonstrated full range gallbladder disease cholecystectomy specimens including 1 neoplastic histology two cases macroscopically occult gallbladder malignancies conclusion routine histological evaluation elective emergency cholecystectomies justified united kingdom population selective analysis potential miss potentially curable life threatening pathology stn","probabilities":0.9799733,"Title":"Incidental Non-Benign Gallbladder Histopathology After Routine Cholecystectomy In A Uk Population","Abstract":"Aim: To analyse the range of histopathology detected in the largest published United Kingdom series of cholecystectomy specimens and to evaluate the rational for selective histopathological analysis. \r\n\r\n Methods: Incidental gallbladder malignancy is rare in the United Kingdom with recent literature supporting selective histological assessment of gallbladders after routine cholecystectomy. All cholecystectomy gallbladder specimens examined by the histopathology department at our hospital during a five year period between March 2008 and March 2013 were retrospectively analysed. Further data was collected on all specimens demonstrating carcinoma, dysplasia and polypoid growths. \r\n\r\n Results: The study included 4027 patients. The majority (97%) of specimens exhibited gallstone or cholecystitis related disease. Polyps were demonstrated in 44 (1.09%), the majority of which were cholesterol based (41/44). Dysplasia, ranging from low to multifocal high-grade was demonstrated in 55 (1.37%). Incidental primary gallbladder adenocarcinoma was detected in 6 specimens (0.15%, 5 female and 1 male), and a single gallbladder revealed carcinoma in situ (0.02%). This large single centre study demonstrated a full range of gallbladder disease from cholecystectomy specimens, including more than 1% neoplastic histology and two cases of macroscopically occult gallbladder malignancies. \r\n\r\n Conclusion: Routine histological evaluation of all elective and emergency cholecystectomies is justified in a United Kingdom population as selective analysis has potential to miss potentially curable life threatening pathology.","Source":"STN","category":"HUMAN","training_data":"Incidental Non-Benign Gallbladder Histopathology After Routine Cholecystectomy In A Uk Population Aim: To analyse the range of histopathology detected in the largest published United Kingdom series of cholecystectomy specimens and to evaluate the rational for selective histopathological analysis. \r\n\r\n Methods: Incidental gallbladder malignancy is rare in the United Kingdom with recent literature supporting selective histological assessment of gallbladders after routine cholecystectomy. All cholecystectomy gallbladder specimens examined by the histopathology department at our hospital during a five year period between March 2008 and March 2013 were retrospectively analysed. Further data was collected on all specimens demonstrating carcinoma, dysplasia and polypoid growths. \r\n\r\n Results: The study included 4027 patients. The majority (97%) of specimens exhibited gallstone or cholecystitis related disease. Polyps were demonstrated in 44 (1.09%), the majority of which were cholesterol based (41/44). Dysplasia, ranging from low to multifocal high-grade was demonstrated in 55 (1.37%). Incidental primary gallbladder adenocarcinoma was detected in 6 specimens (0.15%, 5 female and 1 male), and a single gallbladder revealed carcinoma in situ (0.02%). This large single centre study demonstrated a full range of gallbladder disease from cholecystectomy specimens, including more than 1% neoplastic histology and two cases of macroscopically occult gallbladder malignancies. \r\n\r\n Conclusion: Routine histological evaluation of all elective and emergency cholecystectomies is justified in a United Kingdom population as selective analysis has potential to miss potentially curable life threatening pathology. STN","prediction_labels":"HUMAN"},{"cleaned":"curcumin induces apoptosis gallbladder carcinoma cell line gbc sd cells background gallbladder carcinoma malignant tumor low 5 year survival rate difficulty early diagnosis poor prognosis advanced cancer state aims study determine whether curcumin induce apoptosis gallbladder carcinoma cell line gbc sd clarify related mechanism methods first anti proliferative activities curcumin treated untreated gbc sd cells determined using mtt colony formation assays early apoptosis cells detected annexin v propidium iodide double staining assay hoechst 33342 staining assay detection mitochondrial membrane potential used validate ability curcumin inducing apoptosis gbc sd cells cell cycle changes detected flow cytometric analysis finally expressions apoptosis related proteins genes caspase 3 parp bcl 2 bax analyzed western blot quantitative real time pcr assay statistical analyses performed using student test comparison results obtained cells without curcumin treatment results mtt assay revealed curcumin induced dose time dependent decrease cell viability colony counting indicated curcumin induced dose dependent decrease colony formation ability gbc sd cells cells treated curcumin arrested phase according flow cytometric analysis significant induction early late phases apoptosis shown annexin v fitc pi staining morphological changes apoptotic cells also found hoechst 33342 staining treatment curcumin fluorescence shifted red green m decreased furthermore western blot quantitative real time pcr assays demonstrated curcumin induced apoptosis gbc sd cells regulating ratio bcl 2 bax activating expression cleaved caspase 3 conclusions taken together results indicate curcumin may potential agent treatment gallbladder cancer stn","probabilities":0.9467213,"Title":"Curcumin Induces Apoptosis In Gallbladder Carcinoma Cell Line Gbc-Sd Cells","Abstract":"Background: Gallbladder carcinoma is a malignant tumor with a very low 5-year survival rate because of the difficulty with its early diagnosis and the very poor prognosis of the advanced cancer state. The aims of this study were to determine whether curcumin could induce the apoptosis of a gallbladder carcinoma cell line, GBC-SD, and to clarify its related mechanism. \r\n\r\n Methods: First, the anti-proliferative activities of curcumin-treated and untreated GBC-SD cells were determined using the MTT and colony formation assays. Then, the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay and Hoechst 33342 staining assay. Detection of mitochondrial membrane potential was used to validate the ability of curcumin on inducing apoptosis in GBC-SD cells. Cell cycle changes were detected by flow cytometric analysis. Finally, the expressions of the apoptosis-related proteins or genes caspase-3, PARP, Bcl-2, and Bax were analyzed by western blot and quantitative real time PCR assay. Statistical analyses were performed using the Student's t-test for comparison of the results obtained from cells with or without curcumin treatment. \r\n\r\n Results: The MTT assay revealed that curcumin had induced a dose- and a time-dependent decrease in cell viability. Colony counting indicated that curcumin had induced a dose-dependent decrease in the colony formation ability in GBC-SD cells. Cells treated with curcumin were arrested at the S phase, according to the flow cytometric analysis. A significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. Morphological changes in apoptotic cells were also found by the Hoechst 33342 staining. After treatment with curcumin fluorescence shifted from red to green as ΔΨm decreased. Furthermore, western blot and quantitative real time PCR assays demonstrated that the curcumin induced apoptosis in GBC-SD cells by regulating the ratio of Bcl-2/Bax and activating the expression of cleaved caspase-3. \r\n\r\n Conclusions: Taken together, the results indicate that curcumin may be a potential agent for the treatment of gallbladder cancer.","Source":"STN","category":"ANIMAL","training_data":"Curcumin Induces Apoptosis In Gallbladder Carcinoma Cell Line Gbc-Sd Cells Background: Gallbladder carcinoma is a malignant tumor with a very low 5-year survival rate because of the difficulty with its early diagnosis and the very poor prognosis of the advanced cancer state. The aims of this study were to determine whether curcumin could induce the apoptosis of a gallbladder carcinoma cell line, GBC-SD, and to clarify its related mechanism. \r\n\r\n Methods: First, the anti-proliferative activities of curcumin-treated and untreated GBC-SD cells were determined using the MTT and colony formation assays. Then, the early apoptosis of cells was detected by the annexin V/propidium iodide double-staining assay and Hoechst 33342 staining assay. Detection of mitochondrial membrane potential was used to validate the ability of curcumin on inducing apoptosis in GBC-SD cells. Cell cycle changes were detected by flow cytometric analysis. Finally, the expressions of the apoptosis-related proteins or genes caspase-3, PARP, Bcl-2, and Bax were analyzed by western blot and quantitative real time PCR assay. Statistical analyses were performed using the Student's t-test for comparison of the results obtained from cells with or without curcumin treatment. \r\n\r\n Results: The MTT assay revealed that curcumin had induced a dose- and a time-dependent decrease in cell viability. Colony counting indicated that curcumin had induced a dose-dependent decrease in the colony formation ability in GBC-SD cells. Cells treated with curcumin were arrested at the S phase, according to the flow cytometric analysis. A significant induction of both the early and late phases of apoptosis was shown by the annexin V-FITC and PI staining. Morphological changes in apoptotic cells were also found by the Hoechst 33342 staining. After treatment with curcumin fluorescence shifted from red to green as ΔΨm decreased. Furthermore, western blot and quantitative real time PCR assays demonstrated that the curcumin induced apoptosis in GBC-SD cells by regulating the ratio of Bcl-2/Bax and activating the expression of cleaved caspase-3. \r\n\r\n Conclusions: Taken together, the results indicate that curcumin may be a potential agent for the treatment of gallbladder cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"increased number metastatic lymph nodes adenocarcinoma ampulla vater prognostic factor proposal new nodal classification background although number metastatic lymph nodes gastrointestinal carcinomas correlated inversely prognosis prognostic value number metastatic lymph nodes ampullary adenocarcinoma well characterized methods lymph node metastasis assessed surveillance epidemiology end results database 1 057 ampullary adenocarcinomas operatively resected least 12 lymph nodes examined complex pattern survival versus extent lymph node metastasis captured censored local regression impact extent lymph nodes metastasis survival investigated use k adaptive partitioning algorithm identify significant cut points metastatic lymph nodes affecting survival results two significant cut points 0 2 metastatic lymph node segregated patients 3 groups clinically important differences median survival patients metastatic lymph node 477 cases median survival 91 months patients 1 2 metastatic lymph nodes 279 cases median survival 29 months whereas patients 3 metastatic lymph nodes 301 cases median survival 19 months p 0001 results validated additional single institution dataset 318 cases p 0001 conclusion present results suggest nodal classification ampullary adenocarcinoma categorized n0 metastatic lymph node n1 1 2 metastatic lymph nodes n2 3 metastatic lymph nodes pubmed","probabilities":0.9799733,"Title":"Increased number of metastatic lymph nodes in adenocarcinoma of the ampulla of Vater as a prognostic factor: a proposal of new nodal classification","Abstract":"BACKGROUND: Although the number of metastatic lymph nodes in most gastrointestinal carcinomas is correlated inversely with prognosis, the prognostic value of the number of metastatic lymph nodes in ampullary adenocarcinoma has not been well characterized. METHODS: Lymph node metastasis was assessed in the Surveillance, Epidemiology and End Results database in 1,057 ampullary adenocarcinomas that were operatively resected and for which at least 12 lymph nodes were examined. A complex pattern of survival versus extent of lymph node metastasis was captured by censored local regression. The impact of the extent of lymph nodes metastasis on survival was investigated by use of the K-adaptive partitioning algorithm to identify the most significant cut-off points of metastatic lymph nodes affecting survival. RESULTS: Two significant cut-off points (0 and 2) for the metastatic lymph node segregated patients into 3 groups with clinically important differences in median survival: patients with no metastatic lymph node (477 cases) had a median survival of 91 months, patients with 1-2 metastatic lymph nodes (279 cases) had a median survival of 29 months, whereas patients with ≥3 metastatic Lymph nodes (301 cases) had a median survival of 19 months (P < .0001). These results were validated with additional single institution dataset (318 cases, P < .0001). CONCLUSION: The present results suggest that the nodal classification of ampullary adenocarcinoma should be categorized N0 (no metastatic lymph node), N1 (1-2 metastatic lymph nodes), and N2 (≥3 metastatic lymph nodes).","Source":"PubMed","category":"HUMAN","training_data":"Increased number of metastatic lymph nodes in adenocarcinoma of the ampulla of Vater as a prognostic factor: a proposal of new nodal classification BACKGROUND: Although the number of metastatic lymph nodes in most gastrointestinal carcinomas is correlated inversely with prognosis, the prognostic value of the number of metastatic lymph nodes in ampullary adenocarcinoma has not been well characterized. METHODS: Lymph node metastasis was assessed in the Surveillance, Epidemiology and End Results database in 1,057 ampullary adenocarcinomas that were operatively resected and for which at least 12 lymph nodes were examined. A complex pattern of survival versus extent of lymph node metastasis was captured by censored local regression. The impact of the extent of lymph nodes metastasis on survival was investigated by use of the K-adaptive partitioning algorithm to identify the most significant cut-off points of metastatic lymph nodes affecting survival. RESULTS: Two significant cut-off points (0 and 2) for the metastatic lymph node segregated patients into 3 groups with clinically important differences in median survival: patients with no metastatic lymph node (477 cases) had a median survival of 91 months, patients with 1-2 metastatic lymph nodes (279 cases) had a median survival of 29 months, whereas patients with ≥3 metastatic Lymph nodes (301 cases) had a median survival of 19 months (P < .0001). These results were validated with additional single institution dataset (318 cases, P < .0001). CONCLUSION: The present results suggest that the nodal classification of ampullary adenocarcinoma should be categorized N0 (no metastatic lymph node), N1 (1-2 metastatic lymph nodes), and N2 (≥3 metastatic lymph nodes). PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcomes resection intrahepatic cholangiocarcinoma external validation comparison prognostic models background published prognostic models overall survival liver resection intrahepatic cholangiocarcinoma require external validation use clinical practice study design january 1993 may 2013 consecutive patients underwent resection intrahepatic cholangiocarcinoma identified prospective database wang nomogram derived asian cohort n 367 included clinicopathologic variables preoperative cea cancer antigen 19 9 levels hyder nomogram derived eastern western multicenter cohort n 514 using clinicopathologic variables ajcc cancer staging system 7th ed preoperative fudan risk score also evaluated prognostic performance assessed terms discrimination calibration stratification results one hundred eighty eight patients included median follow 41 months median overall survival 48 7 months estimated 3 year 5 year overall survival rates 59 45 respectively overall survival prediction accuracy according concordance index calculation 0 72 wang nomogram 0 66 hyder nomogram 0 63 ajcc system 0 55 using fudan score nomograms provided effective patient stratification distinct survival groups conclusions wang hyder nomograms provided accurate patient prognosis estimation liver resection intrahepatic cholangiocarcinoma useful decision making adjuvant therapy wang nomogram appears appropriate patients undergoing formal portal lymphadenectomy requires preoperative cea cancer antigen 19 9 levels optimal performance pubmed","probabilities":0.9799733,"Title":"Outcomes after Resection of Intrahepatic Cholangiocarcinoma: External Validation and Comparison of Prognostic Models","Abstract":"BACKGROUND: Published prognostic models for overall survival after liver resection for intrahepatic cholangiocarcinoma require external validation before use in clinical practice. STUDY DESIGN: From January 1993 to May 2013, consecutive patients who underwent resection of intrahepatic cholangiocarcinoma were identified from a prospective database. The Wang nomogram was derived in an Asian cohort (n = 367) and included clinicopathologic variables and preoperative CEA and cancer antigen 19-9 levels. The Hyder nomogram was derived in an Eastern and Western multicenter cohort (n = 514) using clinicopathologic variables only. The AJCC Cancer Staging System (7th ed) and the preoperative Fudan risk score were also evaluated. Prognostic performance was assessed in terms of discrimination, calibration, and stratification. RESULTS: One hundred and eighty-eight patients were included, with a median follow-up of 41 months. Median overall survival was 48.7 months and estimated 3-year and 5-year overall survival rates were 59% and 45%, respectively. Overall survival prediction accuracy, according to concordance-index calculation, was 0.72 with the Wang nomogram, 0.66 with the Hyder nomogram, 0.63 with the AJCC system, and 0.55 using the Fudan score. Both nomograms provided effective patient stratification in distinct survival groups. CONCLUSIONS: Both the Wang and Hyder nomograms provided accurate patient prognosis estimation after liver resection for intrahepatic cholangiocarcinoma and can be useful for decision making about adjuvant therapy. The Wang nomogram appears to be more appropriate in patients undergoing formal portal lymphadenectomy and requires preoperative CEA and cancer antigen 19-9 levels for optimal performance.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes after Resection of Intrahepatic Cholangiocarcinoma: External Validation and Comparison of Prognostic Models BACKGROUND: Published prognostic models for overall survival after liver resection for intrahepatic cholangiocarcinoma require external validation before use in clinical practice. STUDY DESIGN: From January 1993 to May 2013, consecutive patients who underwent resection of intrahepatic cholangiocarcinoma were identified from a prospective database. The Wang nomogram was derived in an Asian cohort (n = 367) and included clinicopathologic variables and preoperative CEA and cancer antigen 19-9 levels. The Hyder nomogram was derived in an Eastern and Western multicenter cohort (n = 514) using clinicopathologic variables only. The AJCC Cancer Staging System (7th ed) and the preoperative Fudan risk score were also evaluated. Prognostic performance was assessed in terms of discrimination, calibration, and stratification. RESULTS: One hundred and eighty-eight patients were included, with a median follow-up of 41 months. Median overall survival was 48.7 months and estimated 3-year and 5-year overall survival rates were 59% and 45%, respectively. Overall survival prediction accuracy, according to concordance-index calculation, was 0.72 with the Wang nomogram, 0.66 with the Hyder nomogram, 0.63 with the AJCC system, and 0.55 using the Fudan score. Both nomograms provided effective patient stratification in distinct survival groups. CONCLUSIONS: Both the Wang and Hyder nomograms provided accurate patient prognosis estimation after liver resection for intrahepatic cholangiocarcinoma and can be useful for decision making about adjuvant therapy. The Wang nomogram appears to be more appropriate in patients undergoing formal portal lymphadenectomy and requires preoperative CEA and cancer antigen 19-9 levels for optimal performance. PubMed","prediction_labels":"HUMAN"},{"cleaned":"anti mica b monoclonal antibody supports antibody dependent cell mediated cytotoxicity intrahepatic cholangiocarcinoma cells abstract available google scholar","probabilities":0.9467213,"Title":"An Anti-Mica/B Monoclonal Antibody Supports Antibody-Dependent Cell-Mediated Cytotoxicity To Intrahepatic Cholangiocarcinoma Cells","Abstract":"Abstract not available","Source":"Google Scholar","category":"ANIMAL","training_data":"An Anti-Mica/B Monoclonal Antibody Supports Antibody-Dependent Cell-Mediated Cytotoxicity To Intrahepatic Cholangiocarcinoma Cells Abstract not available Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"preoperative inflammation prognostic factor gallbladder carcinoma background inflammation frequently accompanies gallbladder carcinoma gbc impact outcome unclear present study investigated impact concomitant inflammation survival patients gbc methods patients undergoing surgery gbc october 2003 may 2009 identified retrospectively prospectively collected database patients classified according whether preoperative inflammation present 65 patients 23 results total 88 patients enrolled differences sex mean age tumour node metastasis tnm stage radicality resection two groups overall 3 year survival rate lower patients preoperative inflammation without 33 versus 73 per cent p 0 001 univariable analysis preoperative inflammation n m category tnm stage radicality surgery tumour differentiation significant prognostic factors presence preoperative inflammation hazard ratio hr 2 38 95 per cent confidence interval 1 04 5 43 lymph node metastases hr 5 23 1 05 26 09 r1 r2 resection hr 3 77 1 47 9 72 independent prognostic factors poor survival conclusion presence preoperative inflammation independent prognostic factor poor survival patients gbc pubmed","probabilities":0.9799733,"Title":"Preoperative inflammation is a prognostic factor for gallbladder carcinoma","Abstract":"BACKGROUND: Inflammation frequently accompanies gallbladder carcinoma (GBC), but its impact on outcome is unclear. The present study investigated the impact of concomitant inflammation on survival of patients with GBC. METHODS: All patients undergoing surgery for GBC between October 2003 and May 2009 were identified retrospectively from a prospectively collected database. Patients were classified according to whether preoperative inflammation was present (65 patients) or not (23). RESULTS: A total of 88 patients were enrolled. There were no differences in sex, mean age, tumour node metastasis (TNM) stage and radicality of resection between the two groups. The overall 3-year survival rate was lower in patients with preoperative inflammation than in those without (33 versus 73 per cent; P = 0·001). In univariable analysis, preoperative inflammation, T, N and M category, TNM stage, radicality of surgery and tumour differentiation were significant prognostic factors. The presence of preoperative inflammation (hazard ratio (HR) 2·38, 95 per cent confidence interval 1·04 to 5·43), lymph node metastases (HR 5·23, 1·05 to 26·09) and R1 or R2 resection (HR 3·77, 1·47 to 9·72) were independent prognostic factors for poor survival. CONCLUSION: The presence of preoperative inflammation is an independent prognostic factor for poor survival in patients with GBC.","Source":"PubMed","category":"HUMAN","training_data":"Preoperative inflammation is a prognostic factor for gallbladder carcinoma BACKGROUND: Inflammation frequently accompanies gallbladder carcinoma (GBC), but its impact on outcome is unclear. The present study investigated the impact of concomitant inflammation on survival of patients with GBC. METHODS: All patients undergoing surgery for GBC between October 2003 and May 2009 were identified retrospectively from a prospectively collected database. Patients were classified according to whether preoperative inflammation was present (65 patients) or not (23). RESULTS: A total of 88 patients were enrolled. There were no differences in sex, mean age, tumour node metastasis (TNM) stage and radicality of resection between the two groups. The overall 3-year survival rate was lower in patients with preoperative inflammation than in those without (33 versus 73 per cent; P = 0·001). In univariable analysis, preoperative inflammation, T, N and M category, TNM stage, radicality of surgery and tumour differentiation were significant prognostic factors. The presence of preoperative inflammation (hazard ratio (HR) 2·38, 95 per cent confidence interval 1·04 to 5·43), lymph node metastases (HR 5·23, 1·05 to 26·09) and R1 or R2 resection (HR 3·77, 1·47 to 9·72) were independent prognostic factors for poor survival. CONCLUSION: The presence of preoperative inflammation is an independent prognostic factor for poor survival in patients with GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"obesity cancer risk emerging biological mechanisms perspectives continuously rising trends obesity related malignancies render disease spectrum public health priority worldwide burden cancer attributable obesity expressed population attributable fraction 11 9 men 13 1 women convincing evidence excess body weight associated increased risk cancer least 13 anatomic sites including endometrial esophageal renal pancreatic adenocarcinomas hepatocellular carcinoma gastric cardia cancer meningioma multiple myeloma colorectal postmenopausal breast ovarian gallbladder thyroid cancers first synopsize current epidemiologic evidence obesity paradox cancer risk mortality role weight gain weight loss modulation cancer risk reliable somatometric indicators obesity cancer research gender differences obesity related cancers critically summarize emerging biological mechanisms linking obesity cancer encompassing insulin resistance abnormalities igf system signaling sex hormones biosynthesis pathway subclinical chronic low grade inflammation oxidative stress alterations adipokine pathophysiology factors deriving ectopic fat deposition microenvironment cellular perturbations including vascular perturbations epithelial mesenchymal transition endoplasmic reticulum stress migrating adipose progenitor cells disruption circadian rhythms dietary nutrients factors potential significance altered intestinal microbiome mechanic factors obesity cancer future perspectives regarding prevention diagnosis therapeutics discussed aim review investigate interplay main potential mechanisms risk factors exerts effects target tissues provoking acquire cancerous phenotype pubmed","probabilities":0.88235295,"Title":"Obesity and cancer risk: Emerging biological mechanisms and perspectives","Abstract":"Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype.","Source":"PubMed","category":"HUMAN","training_data":"Obesity and cancer risk: Emerging biological mechanisms and perspectives Continuously rising trends in obesity-related malignancies render this disease spectrum a public health priority. Worldwide, the burden of cancer attributable to obesity, expressed as population attributable fraction, is 11.9% in men and 13.1% in women. There is convincing evidence that excess body weight is associated with an increased risk for cancer of at least 13 anatomic sites, including endometrial, esophageal, renal and pancreatic adenocarcinomas; hepatocellular carcinoma; gastric cardia cancer; meningioma; multiple myeloma; colorectal, postmenopausal breast, ovarian, gallbladder and thyroid cancers. We first synopsize current epidemiologic evidence; the obesity paradox in cancer risk and mortality; the role of weight gain and weight loss in the modulation of cancer risk; reliable somatometric indicators for obesity and cancer research; and gender differences in obesity related cancers. We critically summarize emerging biological mechanisms linking obesity to cancer encompassing insulin resistance and abnormalities of the IGF-I system and signaling; sex hormones biosynthesis and pathway; subclinical chronic low-grade inflammation and oxidative stress; alterations in adipokine pathophysiology; factors deriving from ectopic fat deposition; microenvironment and cellular perturbations including vascular perturbations, epithelial-mesenchymal transition, endoplasmic reticulum stress and migrating adipose progenitor cells; disruption of circadian rhythms; dietary nutrients; factors with potential significance such as the altered intestinal microbiome; and mechanic factors in obesity and cancer. Future perspectives regarding prevention, diagnosis and therapeutics are discussed. The aim of this review is to investigate how the interplay of these main potential mechanisms and risk factors, exerts their effects on target tissues provoking them to acquire a cancerous phenotype. PubMed","prediction_labels":"HUMAN"},{"cleaned":"diagnostic prognostic biomarkers cholangiocarcinoma high mortality rate cholangiocarcinoma cca due part lack non invasive approaches able accurately detect silent tumour early stages therapeutic options potentially curative may least increase overall survival patients fact majority cca tumours linked known aetiological factor highly compromises monitoring patients risk tumour development also early diagnosis combination clinical biochemical features imaging techniques analysis non specific tumour biomarkers serum commonly used help diagnosis cca tumour biopsy usually required confirm diagnosis moreover prognostic biomarkers currently used clinical setting deserving innovative research international validation consensus important efforts made last years identify accurate non invasive biomarkers using innovative techniques high throughput omics technologies review summarizes discusses advances investigation novel diagnostic prognostic biomarkers cca envisions future directions field research pubmed","probabilities":0.9799733,"Title":"Diagnostic and prognostic biomarkers in cholangiocarcinoma","Abstract":"The high mortality rate of cholangiocarcinoma (CCA) is due, in part, to the lack of non-invasive approaches able to accurately detect this silent tumour at early stages, when therapeutic options can be potentially curative or may at least increase the overall survival of patients. The fact that the majority of CCA tumours are not linked to any known aetiological factor highly compromises the monitoring of patients at risk for tumour development and also their early diagnosis. Combination of clinical/biochemical features, imaging techniques and analysis of non-specific tumour biomarkers in serum are commonly used to help in the diagnosis of CCA, but tumour biopsy is usually required to confirm the diagnosis. Moreover, no prognostic biomarkers are currently used in the clinical setting, deserving more innovative research, and international validation and consensus. Important efforts have been made in the last few years to identify accurate non-invasive biomarkers, by using innovative techniques and high-throughput omics technologies. This review summarizes and discusses the advances in the investigation of novel diagnostic and prognostic biomarkers in CCA and envisions the future directions in this field of research.","Source":"PubMed","category":"HUMAN","training_data":"Diagnostic and prognostic biomarkers in cholangiocarcinoma The high mortality rate of cholangiocarcinoma (CCA) is due, in part, to the lack of non-invasive approaches able to accurately detect this silent tumour at early stages, when therapeutic options can be potentially curative or may at least increase the overall survival of patients. The fact that the majority of CCA tumours are not linked to any known aetiological factor highly compromises the monitoring of patients at risk for tumour development and also their early diagnosis. Combination of clinical/biochemical features, imaging techniques and analysis of non-specific tumour biomarkers in serum are commonly used to help in the diagnosis of CCA, but tumour biopsy is usually required to confirm the diagnosis. Moreover, no prognostic biomarkers are currently used in the clinical setting, deserving more innovative research, and international validation and consensus. Important efforts have been made in the last few years to identify accurate non-invasive biomarkers, by using innovative techniques and high-throughput omics technologies. This review summarizes and discusses the advances in the investigation of novel diagnostic and prognostic biomarkers in CCA and envisions the future directions in this field of research. PubMed","prediction_labels":"HUMAN"},{"cleaned":"regulation pkm2 promote malignancy related adverse prognostic risk factor human gallbladder cancer recently pyruvate kinase m2 pkm2 implicated progression certain cancers might play pivotal roles formation malignancy however role pkm2 gallbladder cancer well investigated study analyzed associations pkm2 expression status various clinical pathologic parameters large cohort gallbladder cancer gbc patients long term follow results expression level pyruvate kinase isotypes gbc tissues adjacent normal gallbladder tissues estimated qrt pcr western blot pkm2 mrna level significantly high gallbladder cancer tissues adjacent noncancerous tissues p 0 001 high expression pkm2 detected 55 71 paraffin embedded gbc tissue high pkm2 expression independently associated poorer overall survival patients gbc median survival 11 9 vs 30 1 months hazard ratio 2 79 95 ci 1 18 6 55 p 0 02 findings indicated elevated expression pkm2 prognostic factor poor gbc clinical outcomes implied involving pkm2 gbc progression stn","probabilities":1.0,"Title":"Up-Regulation Of Pkm2 Promote Malignancy And Related To Adverse Prognostic Risk Factor In Human Gallbladder Cancer","Abstract":"Recently, pyruvate kinase M2 (PKM2) has been implicated in the progression of certain cancers and might play pivotal roles in the formation of malignancy. However, the role of PKM2 in gallbladder cancer had not been well investigated. This study analyzed associations between PKM2 expression status with various clinical and pathologic parameters in a large cohort of gallbladder cancer (GBC) patients from a long term follow up results. The expression level of pyruvate kinase isotypes in GBC tissues and their adjacent normal gallbladder tissues were estimated by qRT-PCR and Western blot. PKM2 mRNA level were significantly high in gallbladder cancer tissues than in adjacent noncancerous tissues (P < 0.001). High expression of the PKM2 was detected in 55.71% paraffin-embedded GBC tissue. The high PKM2 expression was independently associated with poorer overall survival in patients with GBC (median survival 11.9 vs 30.1 months; hazard ratio 2.79; 95% CI = 1.18 to 6.55; P = 0.02). These findings indicated elevated expression of PKM2 is a prognostic factor for poor GBC clinical outcomes, implied involving of PKM2 in GBC progression.","Source":"STN","category":"ANIMAL","training_data":"Up-Regulation Of Pkm2 Promote Malignancy And Related To Adverse Prognostic Risk Factor In Human Gallbladder Cancer Recently, pyruvate kinase M2 (PKM2) has been implicated in the progression of certain cancers and might play pivotal roles in the formation of malignancy. However, the role of PKM2 in gallbladder cancer had not been well investigated. This study analyzed associations between PKM2 expression status with various clinical and pathologic parameters in a large cohort of gallbladder cancer (GBC) patients from a long term follow up results. The expression level of pyruvate kinase isotypes in GBC tissues and their adjacent normal gallbladder tissues were estimated by qRT-PCR and Western blot. PKM2 mRNA level were significantly high in gallbladder cancer tissues than in adjacent noncancerous tissues (P < 0.001). High expression of the PKM2 was detected in 55.71% paraffin-embedded GBC tissue. The high PKM2 expression was independently associated with poorer overall survival in patients with GBC (median survival 11.9 vs 30.1 months; hazard ratio 2.79; 95% CI = 1.18 to 6.55; P = 0.02). These findings indicated elevated expression of PKM2 is a prognostic factor for poor GBC clinical outcomes, implied involving of PKM2 in GBC progression. STN","prediction_labels":"ANIMAL"},{"cleaned":"elevated preoperative neutrophil lymphocyte ratio predicts poor prognosis intrahepatic cholangiocarcinoma patients undergoing hepatectomy high preoperative peripheral blood neutrophil lymphocyte ratio nlr reported predictor poor survival patients various cancers aim study evaluate predictive significance nlr patients undergoing hepatectomy intrahepatic cholangiocarcinoma icc 2005 2011 322 patients underwent hepatectomy icc enrolled retrospective study clinicopathological parameters including nlr evaluated identify predictors overall recurrence free survival hepatectomy best cutoff nlr 2 49 177 322 patients 54 9 nlr 2 49 5 year survival rate hepatectomy 51 1 patients nlr 2 49 24 8 nlr 2 49 p 0 0001 univariate analyses revealed nlr significantly associated recurrence free survival rfs overall survival os p 0 05 multivariable analyses revealed elevated nlr independently predicted poorer os p 0 003 hazard ratio hr 1 600 summary results indicate elevated nlr promising independent predictor poor survival hepatectomy patients icc pubmed","probabilities":0.9799733,"Title":"The elevated preoperative neutrophil-to-lymphocyte ratio predicts poor prognosis in intrahepatic cholangiocarcinoma patients undergoing hepatectomy","Abstract":"A high preoperative peripheral blood neutrophil-to-lymphocyte ratio (NLR) has been reported to be a predictor of poor survival in patients with various cancers. The aim of this study was to evaluate the predictive significance of the NLR in patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). From 2005 to 2011, 322 patients who underwent hepatectomy for ICC were enrolled in this retrospective study. Clinicopathological parameters, including NLR, were evaluated to identify predictors of overall and recurrence-free survival after hepatectomy. The best cutoff for NLR was 2.49, and 177 of 322 patients (54.9 %) had an NLR ≥ 2.49. The 5-year survival rate after hepatectomy was 51.1 % in patients with NLR < 2.49 and 24.8 % in those with NLR ≥ 2.49 (P = 0.0001). Univariate analyses revealed that NLR was significantly associated with recurrence-free survival (RFS) and overall survival (OS; both P < 0.05). Multivariable analyses revealed that elevated NLR independently predicted poorer OS (P = 0.003, hazard ratio [HR] = 1.600). In summary, our results indicate that elevated NLR is a promising independent predictor of poor survival after hepatectomy in patients with ICC.","Source":"PubMed","category":"HUMAN","training_data":"The elevated preoperative neutrophil-to-lymphocyte ratio predicts poor prognosis in intrahepatic cholangiocarcinoma patients undergoing hepatectomy A high preoperative peripheral blood neutrophil-to-lymphocyte ratio (NLR) has been reported to be a predictor of poor survival in patients with various cancers. The aim of this study was to evaluate the predictive significance of the NLR in patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC). From 2005 to 2011, 322 patients who underwent hepatectomy for ICC were enrolled in this retrospective study. Clinicopathological parameters, including NLR, were evaluated to identify predictors of overall and recurrence-free survival after hepatectomy. The best cutoff for NLR was 2.49, and 177 of 322 patients (54.9 %) had an NLR ≥ 2.49. The 5-year survival rate after hepatectomy was 51.1 % in patients with NLR < 2.49 and 24.8 % in those with NLR ≥ 2.49 (P = 0.0001). Univariate analyses revealed that NLR was significantly associated with recurrence-free survival (RFS) and overall survival (OS; both P < 0.05). Multivariable analyses revealed that elevated NLR independently predicted poorer OS (P = 0.003, hazard ratio [HR] = 1.600). In summary, our results indicate that elevated NLR is a promising independent predictor of poor survival after hepatectomy in patients with ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extrahepatic surgically treated klatskin tumors overall better outcomes background objective study investigate incidence demographics tumor characteristics treatment survival patients hilar cholangiocarcinoma methods data klatskin tumors 2004 2013 extracted surveillance epidemiology end results registry epidemiology tumors analyzed results total 254 patients klatskin tumors identified overall age adjusted incidence klatskin tumors 2004 2013 0 38 per 1 000 000 per year gradual decline incidence noted highest 0 44 2005 lowest 0 24 2010 males higher incidence klatskin tumors compared females 0 47 vs 0 25 per 1 000 000 per year tumors common among asian pacific islanders age adjusted incidence rate 0 48 per 1 000 000 incidence increased age peak incidence ages 80 84 years majority tumors extrahepatic 67 3 approximately one fourth 22 4 patients metastatic disease presentation 26 8 patients surgically resectable disease presentation one 5 year cause specific survival klatskin tumors 41 10 4 respectively median survival 7 months cox proportional hazard regression analysis extrahepatic tumors hazard ratio hr 0 54 95 confidence interval ci 0 37 0 80 p 0 02 treated surgically hr 0 47 95 ci 0 29 0 77 p 0 003 significantly better outcomes conclusions klatskin tumors rare poor prognosis low survival rate among tumors extrahepatic surgically treated tumors tend better outcomes stn","probabilities":0.9799733,"Title":"Extrahepatic And Surgically Treated Klatskin Tumors Have Overall Better Outcomes","Abstract":"Background: The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with hilar cholangiocarcinoma. \r\n\r\n Methods: Data on Klatskin tumors between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results Registry. The epidemiology of these tumors was then analyzed. \r\n\r\n Results: A total of 254 patients with Klatskin tumors were identified. The overall age-adjusted incidence of Klatskin tumors between 2004 and 2013 was 0.38 per 1,000,000 per year. A gradual decline in the incidence was noted, with the highest (0.44) in 2005 and lowest (0.24) in 2010. Males had a higher incidence of Klatskin tumors compared to females (0.47 vs. 0.25 per 1,000,000 per year). These tumors were more common among Asian and Pacific islanders, who had an age-adjusted incidence rate of 0.48 per 1,000,000. Incidence increased with age, with the peak incidence between the ages of 80 and 84 years. The majority of the tumors were extrahepatic (67.3%). Approximately one-fourth (22.4%) of these patients had metastatic disease at presentation. Only 26.8% of patients had surgically resectable disease at presentation. One- and 5-year cause-specific survival for Klatskin tumors was 41% and 10.4%, respectively, with a median survival of 7 months. On Cox proportional hazard regression analysis, extrahepatic tumors (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.37-0.80, P=0.02) and those treated surgically (HR 0.47, 95%CI 0.29-0.77, P=0.003) had significantly better outcomes. \r\n\r\n Conclusions: Klatskin tumors are rare and have a very poor prognosis with low survival rate. Among these tumors, extrahepatic and surgically treated tumors tend to have better outcomes.","Source":"STN","category":"HUMAN","training_data":"Extrahepatic And Surgically Treated Klatskin Tumors Have Overall Better Outcomes Background: The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with hilar cholangiocarcinoma. \r\n\r\n Methods: Data on Klatskin tumors between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results Registry. The epidemiology of these tumors was then analyzed. \r\n\r\n Results: A total of 254 patients with Klatskin tumors were identified. The overall age-adjusted incidence of Klatskin tumors between 2004 and 2013 was 0.38 per 1,000,000 per year. A gradual decline in the incidence was noted, with the highest (0.44) in 2005 and lowest (0.24) in 2010. Males had a higher incidence of Klatskin tumors compared to females (0.47 vs. 0.25 per 1,000,000 per year). These tumors were more common among Asian and Pacific islanders, who had an age-adjusted incidence rate of 0.48 per 1,000,000. Incidence increased with age, with the peak incidence between the ages of 80 and 84 years. The majority of the tumors were extrahepatic (67.3%). Approximately one-fourth (22.4%) of these patients had metastatic disease at presentation. Only 26.8% of patients had surgically resectable disease at presentation. One- and 5-year cause-specific survival for Klatskin tumors was 41% and 10.4%, respectively, with a median survival of 7 months. On Cox proportional hazard regression analysis, extrahepatic tumors (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.37-0.80, P=0.02) and those treated surgically (HR 0.47, 95%CI 0.29-0.77, P=0.003) had significantly better outcomes. \r\n\r\n Conclusions: Klatskin tumors are rare and have a very poor prognosis with low survival rate. Among these tumors, extrahepatic and surgically treated tumors tend to have better outcomes. STN","prediction_labels":"HUMAN"},{"cleaned":"role preoperative optimization liver resection patients hilar cholangiocarcinoma type iii background long term survival complete resection hilar cholangiocarcinoma remains disappointing aim retrospective study assess impact liver optimization postoperative outcome hilar cholangiocarcinoma type iii materials methods retrospective single center analysis outcomes patients hilar cholangiocarcinoma type iii underwent resection preoperative liver optimization preoperative transhepatic biliary drainage ptbd bile replacement portal vein embolization pve compared nonoptimized controls results 41 patients undergoing surgery 38 patients undergoing curative intent procedures identified 15 underwent preoperative optimization ptbd direct bilirubin decreased 218 0 184 2 75 9 42 7 mol l p 0 03 trend toward decreased ast alt levels overall 3 5 year survival rates 47 9 9 1 41 9 9 8 primary endpoint 5 year survival surgery significantly different groups preoperative jaundice identified independent prognostic factor poor outcome hazard ratio hr 2 12 p 0 02 four patients 10 5 without preoperative optimization died liver failure within first 30 days postsurgery preceded three cases intra abdominal abscesses ptbd associated lower rate postoperative intra abdominal abscesses however factor independently predictive higher survival conclusion preoperative optimization liver hilar cholangiocarcinoma type iii reduced incidence intra abdominal abscesses impact postoperative survival remains unclear stn","probabilities":0.9799733,"Title":"Role Of Preoperative Optimization Of The Liver For Resection In Patients With Hilar Cholangiocarcinoma Type Iii","Abstract":"Background: Long-term survival after complete resection of hilar cholangiocarcinoma remains disappointing. The aim of this retrospective study was to assess the impact of liver optimization on postoperative outcome of hilar cholangiocarcinoma type III. \r\n\r\n Materials and methods: In a retrospective, single-center analysis, outcomes in patients with hilar cholangiocarcinoma type III who underwent resection after preoperative liver optimization (preoperative transhepatic biliary drainage [PTBD], bile replacement, and/or portal vein embolization [PVE]) were compared with nonoptimized controls. \r\n\r\n Results: Of 41 patients undergoing surgery, 38 patients undergoing curative intent procedures were identified, of whom 15 underwent preoperative optimization. After PTBD, direct bilirubin decreased from 218.0 ± 184.2 to 75.9 ± 42.7 μmol/L (P = 0.03), and there was a trend toward decreased AST and ALT levels. Overall, 3- and 5-year survival rates were 47.9 ± 9.1 and 41.9 ± 9.8%. The primary endpoint, 5-year survival after surgery, was not significantly different between groups. Preoperative jaundice was identified as an independent prognostic factor for poor outcome (hazard ratio [HR] 2.12, P = 0.02). Four patients (10.5%) without preoperative optimization died of liver failure within the first 30 days postsurgery, preceded in three cases by intra-abdominal abscesses. PTBD was associated with a lower rate of postoperative intra-abdominal abscesses; however this factor was not independently predictive of higher survival. \r\n\r\n Conclusion: Preoperative optimization of the liver in hilar cholangiocarcinoma Type III reduced the incidence of intra-abdominal abscesses, but its impact on postoperative survival remains unclear.","Source":"STN","category":"HUMAN","training_data":"Role Of Preoperative Optimization Of The Liver For Resection In Patients With Hilar Cholangiocarcinoma Type Iii Background: Long-term survival after complete resection of hilar cholangiocarcinoma remains disappointing. The aim of this retrospective study was to assess the impact of liver optimization on postoperative outcome of hilar cholangiocarcinoma type III. \r\n\r\n Materials and methods: In a retrospective, single-center analysis, outcomes in patients with hilar cholangiocarcinoma type III who underwent resection after preoperative liver optimization (preoperative transhepatic biliary drainage [PTBD], bile replacement, and/or portal vein embolization [PVE]) were compared with nonoptimized controls. \r\n\r\n Results: Of 41 patients undergoing surgery, 38 patients undergoing curative intent procedures were identified, of whom 15 underwent preoperative optimization. After PTBD, direct bilirubin decreased from 218.0 ± 184.2 to 75.9 ± 42.7 μmol/L (P = 0.03), and there was a trend toward decreased AST and ALT levels. Overall, 3- and 5-year survival rates were 47.9 ± 9.1 and 41.9 ± 9.8%. The primary endpoint, 5-year survival after surgery, was not significantly different between groups. Preoperative jaundice was identified as an independent prognostic factor for poor outcome (hazard ratio [HR] 2.12, P = 0.02). Four patients (10.5%) without preoperative optimization died of liver failure within the first 30 days postsurgery, preceded in three cases by intra-abdominal abscesses. PTBD was associated with a lower rate of postoperative intra-abdominal abscesses; however this factor was not independently predictive of higher survival. \r\n\r\n Conclusion: Preoperative optimization of the liver in hilar cholangiocarcinoma Type III reduced the incidence of intra-abdominal abscesses, but its impact on postoperative survival remains unclear. STN","prediction_labels":"HUMAN"},{"cleaned":"dna methylation alterations bile patients biliary disease purpose need enhance endobiliary cytotechniques molecular marker lesions special significance patients primary sclerosing cholangitis disease predisposing development cholangiocarcinoma ink4a adp ribosylation factor arf locus encodes two tumor suppressor genes p16ink4a p14arf p16ink4a shown major significance cholangiocarcinoma experimental design effort evaluate potential diagnostic role p16ink4a p14arf promoter methylation biliary disease endoscopical obtained bile specimens 71 patients analyzed 26 choledocholithiasis 6 normal results 23 bile duct carcinoma 5 gall bladder carcinoma eleven patients primary sclerosing cholangitis enrolled results merely 6 specimens 2 32 obtained patients without evidence malignant biliary disease 53 5 malignancies 15 28 showed p16 promoter methylation p14 3 46 2 respectively concordance methylation rates detected either bile tissue specimens high primary sclerosing cholangitis similar prevalence methylation detected malignant disease conclusions study demonstrates high frequency specificity ink4a arf methylation malignant biliary disease compared mere cholangitis b capability detect alterations reliably endoscopically obtained bile thus ink4a arf promoter methylation status represents candidate marker endoscopic diagnosis biliary disease stn","probabilities":0.875,"Title":"Dna Methylation Alterations In Bile Of Patients With Biliary Disease","Abstract":"Purpose: There is a need to enhance endobiliary cytotechniques by molecular marker lesions. This is of special significance for patients with primary sclerosing cholangitis, a disease predisposing for the development of cholangiocarcinoma. The INK4a/ADP ribosylation factor (ARF) locus encodes two tumor suppressor genes: p16INK4a and p14ARF. p16INK4a has been shown to be of major significance in cholangiocarcinoma. \r\n\r\n Experimental design: In an effort to evaluate the potential diagnostic role of p16INK4a and p14ARF promoter methylation in biliary disease, endoscopical obtained bile specimens of 71 patients were analyzed (26 choledocholithiasis, 6 with normal results, 23 bile duct carcinoma, 5 gall bladder carcinoma). Eleven patients with primary sclerosing cholangitis were enrolled. \r\n\r\n Results: Merely 6% of specimens (2 of 32) obtained from patients without evidence for malignant biliary disease but 53.5% of malignancies (15 of 28) showed p16 promoter methylation (p14: 3 and 46.2%, respectively). The concordance of methylation rates detected in either bile or tissue specimens was high. In primary sclerosing cholangitis, a similar prevalence of methylation was detected as in malignant disease. \r\n\r\n Conclusions: This study demonstrates: (a) a high frequency and specificity of INK4a/ARF methylation in malignant biliary disease compared with mere cholangitis; and (b) the capability to detect these alterations reliably in endoscopically obtained bile. Thus, INK4a/ARF's promoter methylation status represents a candidate marker for the endoscopic diagnosis of biliary disease.","Source":"STN","category":"ANIMAL","training_data":"Dna Methylation Alterations In Bile Of Patients With Biliary Disease Purpose: There is a need to enhance endobiliary cytotechniques by molecular marker lesions. This is of special significance for patients with primary sclerosing cholangitis, a disease predisposing for the development of cholangiocarcinoma. The INK4a/ADP ribosylation factor (ARF) locus encodes two tumor suppressor genes: p16INK4a and p14ARF. p16INK4a has been shown to be of major significance in cholangiocarcinoma. \r\n\r\n Experimental design: In an effort to evaluate the potential diagnostic role of p16INK4a and p14ARF promoter methylation in biliary disease, endoscopical obtained bile specimens of 71 patients were analyzed (26 choledocholithiasis, 6 with normal results, 23 bile duct carcinoma, 5 gall bladder carcinoma). Eleven patients with primary sclerosing cholangitis were enrolled. \r\n\r\n Results: Merely 6% of specimens (2 of 32) obtained from patients without evidence for malignant biliary disease but 53.5% of malignancies (15 of 28) showed p16 promoter methylation (p14: 3 and 46.2%, respectively). The concordance of methylation rates detected in either bile or tissue specimens was high. In primary sclerosing cholangitis, a similar prevalence of methylation was detected as in malignant disease. \r\n\r\n Conclusions: This study demonstrates: (a) a high frequency and specificity of INK4a/ARF methylation in malignant biliary disease compared with mere cholangitis; and (b) the capability to detect these alterations reliably in endoscopically obtained bile. Thus, INK4a/ARF's promoter methylation status represents a candidate marker for the endoscopic diagnosis of biliary disease. STN","prediction_labels":"ANIMAL"},{"cleaned":"second line chemotherapy patients advanced recurrent biliary tract cancer single center retrospective analysis 294 cases purpose survival benefit first line chemotherapy ct1 biliary tract cancer btc established role second line chemotherapy ct2 fully elucidated yet methods consecutive advanced btc patients receiving ct1 2000 2016 retrospectively studied investigated safety efficacy ct2 prognostic factors residual survival ct1 explored subgroups benefit ct2 results among 294 patients receiving ct1 advanced btc ct2 given 139 patients 47 ct2 provided response rate 4 disease control rate 52 median progression free survival 2 8 overall survival 7 7 months respectively ct2 associated longer residual survival ct1 hazard ratio hr 0 61 p 0 01 well ps 0 1 hr 0 53 p 0 01 best response ct1 pd hr 1 46 p 0 01 cea 5 0 ng ml hr 1 69 p 0 01 effects ct2 homogeneous across almost subgroups prominent patients age 70 years hr 0 32 p interaction 0 02 ca19 9 200 iu ml hr 0 41 p interaction 0 08 cea 5 0 ng ml hr 0 41 p interaction 0 06 conclusions introduction rate ct2 47 although efficacy ct2 modest terms tumor response associated better survival investigations necessary develop effective regimens select patients benefit ct2 pubmed","probabilities":0.9799733,"Title":"Second-line chemotherapy in patients with advanced or recurrent biliary tract cancer: a single center, retrospective analysis of 294 cases","Abstract":"Purpose The survival benefit of first-line chemotherapy (CT1) for biliary tract cancer (BTC) is now established but the role of second-line chemotherapy (CT2) has not been fully elucidated yet. Methods Consecutive advanced BTC patients receiving CT1 between 2000 and 2016 were retrospectively studied. We investigated the safety and efficacy of CT2, prognostic factors for residual survival after CT1, and explored subgroups who would benefit from CT2. Results Among 294 patients receiving CT1 for advanced BTC, CT2 was given in 139 patients (47%). CT2 provided a response rate of 4%, a disease control rate of 52%, a median progression-free survival of 2.8 and overall survival of 7.7 months, respectively. CT2 was associated with longer residual survival after CT1 (hazard ratio [HR] 0.61, p < 0.01), as well as PS of 0-1 (HR 0.53, p < 0.01), best response to CT1 of PD (HR 1.46, p = 0.01), and CEA ≥5.0 ng/mL (HR 1.69, p < 0.01). The effects of CT2 were homogeneous across almost all subgroups but were more prominent in patients with age ≥ 70 years (HR 0.32, p for interaction =0.02), CA19-9 ≥ 200 IU/mL (HR 0.41, p for interaction = 0.08) and CEA ≥5.0 ng/mL (HR 0.41, p for interaction = 0.06). Conclusions The introduction rate of CT2 was 47%. Although the efficacy of CT2 was modest in terms of tumor response, it was associated with better survival. Further investigations are necessary both to develop more effective regimens and to select patients who will benefit from CT2.","Source":"PubMed","category":"HUMAN","training_data":"Second-line chemotherapy in patients with advanced or recurrent biliary tract cancer: a single center, retrospective analysis of 294 cases Purpose The survival benefit of first-line chemotherapy (CT1) for biliary tract cancer (BTC) is now established but the role of second-line chemotherapy (CT2) has not been fully elucidated yet. Methods Consecutive advanced BTC patients receiving CT1 between 2000 and 2016 were retrospectively studied. We investigated the safety and efficacy of CT2, prognostic factors for residual survival after CT1, and explored subgroups who would benefit from CT2. Results Among 294 patients receiving CT1 for advanced BTC, CT2 was given in 139 patients (47%). CT2 provided a response rate of 4%, a disease control rate of 52%, a median progression-free survival of 2.8 and overall survival of 7.7 months, respectively. CT2 was associated with longer residual survival after CT1 (hazard ratio [HR] 0.61, p < 0.01), as well as PS of 0-1 (HR 0.53, p < 0.01), best response to CT1 of PD (HR 1.46, p = 0.01), and CEA ≥5.0 ng/mL (HR 1.69, p < 0.01). The effects of CT2 were homogeneous across almost all subgroups but were more prominent in patients with age ≥ 70 years (HR 0.32, p for interaction =0.02), CA19-9 ≥ 200 IU/mL (HR 0.41, p for interaction = 0.08) and CEA ≥5.0 ng/mL (HR 0.41, p for interaction = 0.06). Conclusions The introduction rate of CT2 was 47%. Although the efficacy of CT2 was modest in terms of tumor response, it was associated with better survival. Further investigations are necessary both to develop more effective regimens and to select patients who will benefit from CT2. PubMed","prediction_labels":"HUMAN"},{"cleaned":"optimal indications additional resection invasive cancer positive proximal bile duct margin cases advanced perihilar cholangiocarcinoma background survival benefits additional resection positive proximal ductal margin cases perihilar cholangiocarcinoma remain elucidated purpose retrospective study clarify optimal indications additional resection invasive cancer positive proximal ductal margin pm methods patients underwent hepatectomy perihilar cholangiocarcinoma 2000 2011 analyzed surgical variables status pm prognostic factors survival evaluated results total 224 patients enrolled additional resection performed 52 75 positive pms invasive cancer resulting 43 negative pms survival patients negative pm treated additional resection n 43 significantly worse patients negative pm treated without additional resection n 149 p 0 031 significantly differ patients positive pm n 32 p 0 215 multivariate analysis demonstrated carbohydrate antigen 19 9 ca19 9 level 64 64 combined vascular resection pn pm histological grade perineural invasion liver invasion r status independent prognostic factors subgroups ca19 9 64 pm0 survival patients negative pm treated additional resection significantly better patients positive pm p 0 019 p 0 021 respectively conclusions additional resection invasive cancer positive pms may warranted limited patients lower level ca19 9 distant metastatic disease pubmed","probabilities":0.9799733,"Title":"Optimal indications for additional resection of the invasive cancer-positive proximal bile duct margin in cases of advanced perihilar cholangiocarcinoma","Abstract":"BACKGROUND: The survival benefits of additional resection of the positive proximal ductal margin in cases of perihilar cholangiocarcinoma remain to be elucidated. The purpose of this retrospective study was to clarify the optimal indications for additional resection of the invasive cancer-positive proximal ductal margin (PM) METHODS: All patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2011 were analyzed. Surgical variables, the status of the PM, prognostic factors, and survival were evaluated. RESULTS: A total of 224 patients were enrolled. Additional resection was performed in 52 of 75 positive PMs of invasive cancer, resulting in 43 negative PMs. The survival of patients with a negative PM treated with additional resection (n = 43) was significantly worse than that of the patients with a negative PM treated without additional resection (n = 149; P = 0.031) and did not significantly differ from that of the patients with a positive PM (n = 32; P = 0.215). A multivariate analysis demonstrated that the carbohydrate antigen 19-9 (CA19-9) level (<64 or ≥64), combined vascular resection, pN, pM, the histological grade, perineural invasion, liver invasion, and R status were independent prognostic factors. Only in the subgroups of CA19-9 < 64 and pM0, the survival of the patients with a negative PM treated with additional resection was significantly better than that of the patients with a positive PM (P = 0.019 and P = 0.021, respectively). CONCLUSIONS: Additional resection of the invasive cancer-positive PMs may be warranted only in limited patients with a lower level of CA19-9 and no distant metastatic disease.","Source":"PubMed","category":"HUMAN","training_data":"Optimal indications for additional resection of the invasive cancer-positive proximal bile duct margin in cases of advanced perihilar cholangiocarcinoma BACKGROUND: The survival benefits of additional resection of the positive proximal ductal margin in cases of perihilar cholangiocarcinoma remain to be elucidated. The purpose of this retrospective study was to clarify the optimal indications for additional resection of the invasive cancer-positive proximal ductal margin (PM) METHODS: All patients who underwent hepatectomy for perihilar cholangiocarcinoma between 2000 and 2011 were analyzed. Surgical variables, the status of the PM, prognostic factors, and survival were evaluated. RESULTS: A total of 224 patients were enrolled. Additional resection was performed in 52 of 75 positive PMs of invasive cancer, resulting in 43 negative PMs. The survival of patients with a negative PM treated with additional resection (n = 43) was significantly worse than that of the patients with a negative PM treated without additional resection (n = 149; P = 0.031) and did not significantly differ from that of the patients with a positive PM (n = 32; P = 0.215). A multivariate analysis demonstrated that the carbohydrate antigen 19-9 (CA19-9) level (<64 or ≥64), combined vascular resection, pN, pM, the histological grade, perineural invasion, liver invasion, and R status were independent prognostic factors. Only in the subgroups of CA19-9 < 64 and pM0, the survival of the patients with a negative PM treated with additional resection was significantly better than that of the patients with a positive PM (P = 0.019 and P = 0.021, respectively). CONCLUSIONS: Additional resection of the invasive cancer-positive PMs may be warranted only in limited patients with a lower level of CA19-9 and no distant metastatic disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative biliary drainage versus direct surgery perihilar cholangiocarcinoma retrospective study single center perihilar cholangiocarcinoma pcc also known klatskin tumor common type cholangiocarcinoma cc preoperative biliary drainage pbd indicated pcc patients acute cholangitis patients need portal vein embolization pve however routine performance pbd patients pcc still controversial current study retrospectively examined patients pcc undergo pve cholangitis seen hospital assess advantages disadvantages pbd study also sought find optimal value total bilirubin tb indicate performing pbd 2009 2014 excluding patients acute cholangitis pve patients undergone hepatectomy pcc enrolled study first surgical outcomes postoperative outcomes compared pbd group direct surgery group second roc curve analysis subgroup patients performed find best cut value tb indicating pbd third costs patients including total charges charges per day compared two groups subjects 218 patients total fifty five patients underwent pbd group longer operative time 390 210 700 vs 360 105 730 min p 0 013 longer hospital stay 20 9 48 vs 17 6 93 days p 0 007 underwent vascular resection reconstruction less often 8 14 5 vs 50 30 7 p 0 019 mortality morbidity comparable two groups roc curve analysis subgroup patients indicated cut value total bilirubin 218 75 mol l 12 4 mg dl total hospital charges charges per day differ significantly two groups disadvantages pbd longer operating time longer duration hospitalization short term surgical outcomes hospital charges pbd group comparable direct surgery group pbd considered patients diagnosis still suspicious pcc based current data optimal cut value preoperative tb 218 75 mol l 12 4 mg dl indicate pbd patients pcc pubmed","probabilities":0.9799733,"Title":"Preoperative biliary drainage versus direct surgery for perihilar cholangiocarcinoma: A retrospective study at a single center","Abstract":"Perihilar cholangiocarcinoma (pCC, also known as a Klatskin tumor) is the most common type of cholangiocarcinoma (CC). Preoperative biliary drainage (PBD) is indicated for pCC patients with acute cholangitis or patients who need portal vein embolization (PVE). However, the routine performance of PBD in other patients with pCC is still controversial. The current study retrospectively examined patients with pCC who did not undergo PVE and who did not have cholangitis who were seen at this Hospital to assess the advantages and disadvantages of PBD. This study also sought to find an optimal value of total bilirubin (TB) to indicate performing PBD. Between 2009 and 2014, after excluding patients with acute cholangitis and PVE, patients who had undergone hepatectomy for pCC were enrolled in this study. First, the surgical outcomes and postoperative outcomes were compared between PBD group and direct surgery group. Second, ROC curve analysis of a subgroup of patients was performed to find the best cut off value of TB for indicating the PBD. Third, the costs for patients, including the total charges and the charges per day were compared between the two groups. Subjects were 218 patients in total. Fifty-five patients underwent PBD. This group had a longer operative time [390 (210-700) vs. 360 (105-730) min, p = 0.013], and a longer hospital stay [20 (9-48) vs. 17 (6-93) days, p = 0.007], but underwent vascular resection and reconstruction less often [8 (14.5%) vs. 50 (30.7%), p = 0.019]. Mortality and morbidity were comparable between the two groups. ROC curve analysis of a subgroup of patients indicated that the cut-off value for total bilirubin was 218.75 μmol/L (12.4 mg/dL). The total hospital charges and the charges per day did not differ significantly for the two groups. Disadvantages of PBD were a longer operating time and a longer duration of hospitalization, but the short-term surgical outcomes and hospital charges of PBD group were comparable to the direct surgery group. PBD should be considered for patients when the diagnosis is still suspicious of pCC. Based on the current data, the optimal cut-off value for preoperative TB was 218.75 μmol/L (12.4 mg/dL) to indicate PBD for patients with pCC.","Source":"PubMed","category":"HUMAN","training_data":"Preoperative biliary drainage versus direct surgery for perihilar cholangiocarcinoma: A retrospective study at a single center Perihilar cholangiocarcinoma (pCC, also known as a Klatskin tumor) is the most common type of cholangiocarcinoma (CC). Preoperative biliary drainage (PBD) is indicated for pCC patients with acute cholangitis or patients who need portal vein embolization (PVE). However, the routine performance of PBD in other patients with pCC is still controversial. The current study retrospectively examined patients with pCC who did not undergo PVE and who did not have cholangitis who were seen at this Hospital to assess the advantages and disadvantages of PBD. This study also sought to find an optimal value of total bilirubin (TB) to indicate performing PBD. Between 2009 and 2014, after excluding patients with acute cholangitis and PVE, patients who had undergone hepatectomy for pCC were enrolled in this study. First, the surgical outcomes and postoperative outcomes were compared between PBD group and direct surgery group. Second, ROC curve analysis of a subgroup of patients was performed to find the best cut off value of TB for indicating the PBD. Third, the costs for patients, including the total charges and the charges per day were compared between the two groups. Subjects were 218 patients in total. Fifty-five patients underwent PBD. This group had a longer operative time [390 (210-700) vs. 360 (105-730) min, p = 0.013], and a longer hospital stay [20 (9-48) vs. 17 (6-93) days, p = 0.007], but underwent vascular resection and reconstruction less often [8 (14.5%) vs. 50 (30.7%), p = 0.019]. Mortality and morbidity were comparable between the two groups. ROC curve analysis of a subgroup of patients indicated that the cut-off value for total bilirubin was 218.75 μmol/L (12.4 mg/dL). The total hospital charges and the charges per day did not differ significantly for the two groups. Disadvantages of PBD were a longer operating time and a longer duration of hospitalization, but the short-term surgical outcomes and hospital charges of PBD group were comparable to the direct surgery group. PBD should be considered for patients when the diagnosis is still suspicious of pCC. Based on the current data, the optimal cut-off value for preoperative TB was 218.75 μmol/L (12.4 mg/dL) to indicate PBD for patients with pCC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ww domain containing oxidoreductase induces apoptosis gallbladder derived malignant cell upregulating expression p73 puma gallbladder cancer gbc one leading cause cancer related death worldwide ww domain containing oxidoreductase wwox tumor suppressor gene suppress proliferation variety tumors however little known relationships wwox gallbladder cancer current study intended investigate tumor suppressive role wwox gallbladder malignant cells vitro vivo explore potential mechanism tumor toxic function wwox results shown wwox triggerred apoptosis gbc cells increased expression p73 puma cytoplasm also found bax upregulated overexpression wwox whereas bcl 2 downregulated wwox validate results vivo evaluated tumor suppressive role wwox mouse model gallbladder cancer results shown proliferation tumor inhibited delivery wwox expressions p73 puma upregulated target tissues mice models administrated wwox shown better prognosis mice negative control groups results study indicated wwox used therapeutic agent gene therapy gallbladder cancer stn","probabilities":0.9467213,"Title":"Ww Domain Containing Oxidoreductase Induces Apoptosis In Gallbladder-Derived Malignant Cell By Upregulating Expression Of P73 And Puma","Abstract":"Gallbladder cancer (GBC) is one leading cause of cancer-related death worldwide. WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene which can suppress proliferation of a variety of tumors. However, little was known about the relationships between WWOX and gallbladder cancer. In the current study, we intended to investigate the tumor suppressive role of WWOX in gallbladder malignant cells both in vitro and in vivo, and explore the potential mechanism of tumor toxic function of WWOX. Our results have shown that WWOX triggerred apoptosis in GBC cells and increased the expression of P73 and PUMA in cytoplasm. We also have found that Bax has been upregulated after overexpression of WWOX, whereas, Bcl-2 was downregulated by WWOX. To further validate the results in vivo, we evaluated the tumor suppressive role of WWOX in mouse model of gallbladder cancer. The results have shown that the proliferation of the tumor was inhibited after delivery of WWOX, and the expressions of P73 and PUMA were upregulated in target tissues. The mice models administrated with WWOX have shown better prognosis than mice in negative control groups. The results from our study indicated that WWOX could be used as a therapeutic agent in the gene therapy of gallbladder cancer.","Source":"STN","category":"ANIMAL","training_data":"Ww Domain Containing Oxidoreductase Induces Apoptosis In Gallbladder-Derived Malignant Cell By Upregulating Expression Of P73 And Puma Gallbladder cancer (GBC) is one leading cause of cancer-related death worldwide. WW domain-containing oxidoreductase (WWOX) is a tumor suppressor gene which can suppress proliferation of a variety of tumors. However, little was known about the relationships between WWOX and gallbladder cancer. In the current study, we intended to investigate the tumor suppressive role of WWOX in gallbladder malignant cells both in vitro and in vivo, and explore the potential mechanism of tumor toxic function of WWOX. Our results have shown that WWOX triggerred apoptosis in GBC cells and increased the expression of P73 and PUMA in cytoplasm. We also have found that Bax has been upregulated after overexpression of WWOX, whereas, Bcl-2 was downregulated by WWOX. To further validate the results in vivo, we evaluated the tumor suppressive role of WWOX in mouse model of gallbladder cancer. The results have shown that the proliferation of the tumor was inhibited after delivery of WWOX, and the expressions of P73 and PUMA were upregulated in target tissues. The mice models administrated with WWOX have shown better prognosis than mice in negative control groups. The results from our study indicated that WWOX could be used as a therapeutic agent in the gene therapy of gallbladder cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"new horizons precision medicine biliary tract cancers biliary tract cancers btc including cholangiocarcinoma gallbladder cancer poor prognosis low incidence cancers although incidence intrahepatic cholangiocarcinoma rising minority patients present resectable disease relapse rates high benefit adjuvant capecitabine chemotherapy demonstrated cisplatin gemcitabine combination chemotherapy emerged reference first line treatment regimen standard second line therapy selected patients may suitable liver directed therapy e g radioembolization external beam radiation pending confirmation benefit randomized studies initial trials targeting epithelial growth factor receptor angiogenesis pathways failed deliver new treatments emerging data next generation sequencing analyses identified actionable mutations e g fgfr fusion rearrangements idh1 idh2 mutations several targeted drugs entering clinical development encouraging results role systemic therapies including targeted therapies immunotherapy btc rapidly evolving subject review significance authors address genetic drivers molecular biology translational perspective intent offer clear view recent past present future btc review describes state art update current status future directions research therapy advanced btc cancer discov 7 9 943 62 2017 aacr pubmed","probabilities":0.9799733,"Title":"New Horizons for Precision Medicine in Biliary Tract Cancers","Abstract":"Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e.g., radioembolization or external beam radiation), pending confirmation of benefit in randomized studies. Initial trials targeting the epithelial growth factor receptor and angiogenesis pathways have failed to deliver new treatments. Emerging data from next-generation sequencing analyses have identified actionable mutations (e.g., FGFR fusion rearrangements and IDH1 and IDH2 mutations), with several targeted drugs entering clinical development with encouraging results. The role of systemic therapies, including targeted therapies and immunotherapy for BTC, is rapidly evolving and is the subject of this review.Significance: The authors address genetic drivers and molecular biology from a translational perspective, in an intent to offer a clear view of the recent past, present, and future of BTC. The review describes a state-of-the-art update of the current status and future directions of research and therapy in advanced BTC. Cancer Discov; 7(9); 943-62. ©2017 AACR.","Source":"PubMed","category":"HUMAN","training_data":"New Horizons for Precision Medicine in Biliary Tract Cancers Biliary tract cancers (BTC), including cholangiocarcinoma and gallbladder cancer, are poor-prognosis and low-incidence cancers, although the incidence of intrahepatic cholangiocarcinoma is rising. A minority of patients present with resectable disease but relapse rates are high; benefit from adjuvant capecitabine chemotherapy has been demonstrated. Cisplatin/gemcitabine combination chemotherapy has emerged as the reference first-line treatment regimen; there is no standard second-line therapy. Selected patients may be suitable for liver-directed therapy (e.g., radioembolization or external beam radiation), pending confirmation of benefit in randomized studies. Initial trials targeting the epithelial growth factor receptor and angiogenesis pathways have failed to deliver new treatments. Emerging data from next-generation sequencing analyses have identified actionable mutations (e.g., FGFR fusion rearrangements and IDH1 and IDH2 mutations), with several targeted drugs entering clinical development with encouraging results. The role of systemic therapies, including targeted therapies and immunotherapy for BTC, is rapidly evolving and is the subject of this review.Significance: The authors address genetic drivers and molecular biology from a translational perspective, in an intent to offer a clear view of the recent past, present, and future of BTC. The review describes a state-of-the-art update of the current status and future directions of research and therapy in advanced BTC. Cancer Discov; 7(9); 943-62. ©2017 AACR. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative endoscopic biliary drainage may negatively impact survival following pancreatoduodenectomy ampullary cancer background aims ampullary carcinoma rare tumour high resectability rate increasing body evidence indicating tumour related factors also jaundice influence survival following curative resection several modalities preoperative biliary drainage available however routine preoperative endoscopic biliary drainage pebd recommended sufficient data regarding impact pebd long term outcomes aim study identify predictive factors survival special regard pebd patients undergoing curative resection ampullary carcinoma patients methods data 64 consecutive patients adenocarcinoma papilla vater operated analysed overall survival defined date surgery date death censored last patient contact survival analysis determined means kaplan meier method significance demographic clinical histopathologic factors ascertained log rank test cox proportional hazard model used determine independent prognostic factors survival results twenty patients 31 2 underwent pebd univariate analysis revealed tumour related factors age 70 pebd negatively influence survival five excluding stage identified independent prognosticators pebd appeared decisive factor median survival patients underwent pebd 25 3 months compared 112 9 months conclusion pebd negatively affected long term outcomes patients resected ampullary carcinoma stn","probabilities":0.9799733,"Title":"Preoperative Endoscopic Biliary Drainage May Negatively Impact Survival Following Pancreatoduodenectomy For Ampullary Cancer","Abstract":"Background/aims: Ampullary carcinoma is a rare tumour with a high resectability rate. There is an increasing body of evidence indicating not only tumour-related factors, but also jaundice influence survival following curative resection. Several modalities for preoperative biliary drainage are available; however, routine preoperative endoscopic biliary drainage (PEBD) is not recommended. There is no sufficient data regarding the impact of PEBD on long-term outcomes. The aim of our study was to identify predictive factors of survival with special regard to PEBD in patients undergoing curative resection for ampullary carcinoma. \n\n Patients and methods: Data from 64 consecutive patients with adenocarcinoma of the papilla of Vater who have been operated on was analysed. Overall survival was defined from the date of surgery to the date of death, or censored at the last patient contact. Survival analysis was determined by means of the Kaplan-Meier method. The significance of the demographic, clinical and histopathologic factors was ascertained by the log-rank test. A Cox proportional hazard model was used to determine independent prognostic factors of survival. \n\n Results: Twenty patients (31.2%) underwent PEBD. Univariate analysis revealed tumour-related factors, age over 70, and PEBD to negatively influence survival. Five of them (excluding T stage) were identified as the independent prognosticators, while PEBD appeared to be the most decisive factor. Median survival for patients who underwent PEBD was 25.3 months as compared to 112.9 months for those who did not. In conclusion, PEBD negatively affected long-term outcomes in our patients with resected ampullary carcinoma.","Source":"STN","category":"HUMAN","training_data":"Preoperative Endoscopic Biliary Drainage May Negatively Impact Survival Following Pancreatoduodenectomy For Ampullary Cancer Background/aims: Ampullary carcinoma is a rare tumour with a high resectability rate. There is an increasing body of evidence indicating not only tumour-related factors, but also jaundice influence survival following curative resection. Several modalities for preoperative biliary drainage are available; however, routine preoperative endoscopic biliary drainage (PEBD) is not recommended. There is no sufficient data regarding the impact of PEBD on long-term outcomes. The aim of our study was to identify predictive factors of survival with special regard to PEBD in patients undergoing curative resection for ampullary carcinoma. \n\n Patients and methods: Data from 64 consecutive patients with adenocarcinoma of the papilla of Vater who have been operated on was analysed. Overall survival was defined from the date of surgery to the date of death, or censored at the last patient contact. Survival analysis was determined by means of the Kaplan-Meier method. The significance of the demographic, clinical and histopathologic factors was ascertained by the log-rank test. A Cox proportional hazard model was used to determine independent prognostic factors of survival. \n\n Results: Twenty patients (31.2%) underwent PEBD. Univariate analysis revealed tumour-related factors, age over 70, and PEBD to negatively influence survival. Five of them (excluding T stage) were identified as the independent prognosticators, while PEBD appeared to be the most decisive factor. Median survival for patients who underwent PEBD was 25.3 months as compared to 112.9 months for those who did not. In conclusion, PEBD negatively affected long-term outcomes in our patients with resected ampullary carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"enhanced expression lncrna tp73 as1 predicts adverse phenotypes cholangiocarcinoma exerts oncogenic properties vitro vivo cholangiocarcinoma cca one aggressive malignancies increasing incidence worldwide various evidence documents abnormally expressed long non coding rnas lncrnas play important roles tumorigenesis progression tp73 as1 novel cancer related lncrna contributes development several malignancies however clinical value potential effects cca remains unknown rt qpcr used measure expression levels tp73 as1 cca tissues paired non tumor tissues association tp73 as1 expression clinicopathological characteristics analyzed addition functional roles tp73 as1 cca detected vitro vivo results illustrated tp73 as1 transcription enhanced cca tissue samples cell lines upregulation closely associated larger tumor size p 0 008 advanced tnm stage p 0 026 patients cca part functional assays silencing tp73 as1 attenuate cca cell growth vitro vivo additionally silencing tp73 as1 facilitates apoptosis via activating caspase 3 caspase 9 importantly tp73 as1 expression affect hibec cell growth apoptosis moreover tp73 as1 also facilitate migration invasion potential cca cells collectively findings may help develop potential therapeutic target patients cca stn","probabilities":0.9467213,"Title":"Enhanced Expression Of Lncrna Tp73-As1 Predicts Adverse Phenotypes For Cholangiocarcinoma And Exerts Oncogenic Properties In Vitro And In Vivo","Abstract":"Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with increasing incidence worldwide. Various evidence documents that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression. TP73-AS1 is a novel cancer-related lncRNA that contributes to the development of several malignancies. However, its clinical value and potential effects on CCA remains unknown. RT-qPCR was used to measure the expression levels of TP73-AS1 in CCA tissues and paired non-tumor tissues and the association between TP73-AS1 expression and clinicopathological characteristics was analyzed. In addition, the functional roles of TP73-AS1 in CCA were detected both in vitro and in vivo. The results illustrated that TP73-AS1 transcription is enhanced in both CCA tissue samples and cell lines, and this upregulation is closely associated with larger tumor size (p=0.008) and advanced TNM stage (p=0.026) in patients with CCA. For the part of functional assays, silencing of TP73-AS1 could attenuate CCA cell growth both in vitro and in vivo. Additionally, silencing of TP73-AS1 facilitates apoptosis via activating caspase-3 and caspase-9. Importantly, TP73-AS1 expression did not affect HIBEC cell growth and apoptosis. Moreover, TP73-AS1 could also facilitate migration and invasion potential of CCA cells. Collectively, these findings may help to develop a potential therapeutic target for the patients with CCA.","Source":"STN","category":"ANIMAL","training_data":"Enhanced Expression Of Lncrna Tp73-As1 Predicts Adverse Phenotypes For Cholangiocarcinoma And Exerts Oncogenic Properties In Vitro And In Vivo Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with increasing incidence worldwide. Various evidence documents that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression. TP73-AS1 is a novel cancer-related lncRNA that contributes to the development of several malignancies. However, its clinical value and potential effects on CCA remains unknown. RT-qPCR was used to measure the expression levels of TP73-AS1 in CCA tissues and paired non-tumor tissues and the association between TP73-AS1 expression and clinicopathological characteristics was analyzed. In addition, the functional roles of TP73-AS1 in CCA were detected both in vitro and in vivo. The results illustrated that TP73-AS1 transcription is enhanced in both CCA tissue samples and cell lines, and this upregulation is closely associated with larger tumor size (p=0.008) and advanced TNM stage (p=0.026) in patients with CCA. For the part of functional assays, silencing of TP73-AS1 could attenuate CCA cell growth both in vitro and in vivo. Additionally, silencing of TP73-AS1 facilitates apoptosis via activating caspase-3 and caspase-9. Importantly, TP73-AS1 expression did not affect HIBEC cell growth and apoptosis. Moreover, TP73-AS1 could also facilitate migration and invasion potential of CCA cells. Collectively, these findings may help to develop a potential therapeutic target for the patients with CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"improved survival surgically resected distal cholangiocarcinoma treated adjuvant therapy propensity score matched analysis background data efficacy adjuvant therapy distal cholangiocarcinoma dcca limited study aimed determine role resected dcca identify subgroups benefit methods conducted retrospective review surgically resected dcca ncdb 2004 2013 patients received observation ob matched propensity score log rank test used compare os results 1782 patients resected dcca 840 47 ob group 942 53 group younger 64 0 vs 68 7 years p 0 001 less comorbidities charlson deyo score 0 74 6 vs 68 0 p 0 001 likely private insurance p 0 001 likely present t3 t4 stage 72 vs 57 p 0 001 n1 n2 disease 58 vs 37 p 0 001 positive surgical margins 26 vs 16 p 0 001 1 1 propensity score matching 500 ob 500 patients compared associated better os hr 0 79 95 ci 0 67 0 93 median os 31 25 months ob p 0 006 1 3 5 year survival rates 87 46 31 79 39 24 ob subgroup analysis revealed associated survival advantage t3 t4 tumors hr 0 72 95 ci 0 59 0 89 node positive disease hr 0 70 95 ci 0 56 0 87 positive margins hr 0 58 95 ci 0 42 0 81 conclusion associated improved os resected dcca especially t3 t4 tumors node positive disease positive margins pubmed","probabilities":0.9799733,"Title":"Improved Survival in Surgically Resected Distal Cholangiocarcinoma Treated with Adjuvant Therapy: a Propensity Score Matched Analysis","Abstract":"BACKGROUND: Data on the efficacy of adjuvant therapy (AT) in distal cholangiocarcinoma (dCCA) is limited. This study aimed to determine the role of AT in resected dCCA and identify subgroups that benefit from AT. METHODS: We conducted a retrospective review of surgically resected dCCA in the NCDB from 2004 to 2013. Patients who received AT or observation (OB) were matched by propensity score. Log-rank test was used to compare OS. RESULTS: Of 1782 patients with resected dCCA, 840 (47%) were in the OB group and 942 (53%) in the AT group. AT was younger (64.0 vs. 68.7 years, p < 0.001), had less comorbidities (Charlson Deyo score 0) (74.6 vs. 68.0%, p < 0.001), and more likely to have private insurance (p < 0.001). AT was more likely to present with T3/T4 stage (72 vs. 57%, p < 0.001), N1/N2 disease (58 vs. 37%, p < 0.001), and positive surgical margins (26 vs. 16%, p < 0.001). After 1:1 propensity score matching, 500 OB and 500 AT patients were compared. AT was associated with better OS (HR 0.79; 95% CI 0.67-0.93). Median OS was 31 and 25 months for the AT and OB (p = 0.006). The 1-, 3-, and 5-year survival rates were 87, 46, and 31% for AT; 79, 39, and 24% for OB. Subgroup analysis revealed an associated survival advantage for AT in T3/T4 tumors (HR = 0.72; 95% CI 0.59-0.89), node positive disease (HR 0.70; 95% CI 0.56-0.87), and positive margins (HR 0.58; 95% CI 0.42-0.81). CONCLUSION: AT is associated with improved OS in resected dCCA, especially in T3/T4 tumors, node positive disease, and positive margins.","Source":"PubMed","category":"HUMAN","training_data":"Improved Survival in Surgically Resected Distal Cholangiocarcinoma Treated with Adjuvant Therapy: a Propensity Score Matched Analysis BACKGROUND: Data on the efficacy of adjuvant therapy (AT) in distal cholangiocarcinoma (dCCA) is limited. This study aimed to determine the role of AT in resected dCCA and identify subgroups that benefit from AT. METHODS: We conducted a retrospective review of surgically resected dCCA in the NCDB from 2004 to 2013. Patients who received AT or observation (OB) were matched by propensity score. Log-rank test was used to compare OS. RESULTS: Of 1782 patients with resected dCCA, 840 (47%) were in the OB group and 942 (53%) in the AT group. AT was younger (64.0 vs. 68.7 years, p < 0.001), had less comorbidities (Charlson Deyo score 0) (74.6 vs. 68.0%, p < 0.001), and more likely to have private insurance (p < 0.001). AT was more likely to present with T3/T4 stage (72 vs. 57%, p < 0.001), N1/N2 disease (58 vs. 37%, p < 0.001), and positive surgical margins (26 vs. 16%, p < 0.001). After 1:1 propensity score matching, 500 OB and 500 AT patients were compared. AT was associated with better OS (HR 0.79; 95% CI 0.67-0.93). Median OS was 31 and 25 months for the AT and OB (p = 0.006). The 1-, 3-, and 5-year survival rates were 87, 46, and 31% for AT; 79, 39, and 24% for OB. Subgroup analysis revealed an associated survival advantage for AT in T3/T4 tumors (HR = 0.72; 95% CI 0.59-0.89), node positive disease (HR 0.70; 95% CI 0.56-0.87), and positive margins (HR 0.58; 95% CI 0.42-0.81). CONCLUSION: AT is associated with improved OS in resected dCCA, especially in T3/T4 tumors, node positive disease, and positive margins. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role tumour microenvironment new vision cholangiocarcinoma cholangiocarcinoma cca relatively rare malignant lethal tumour derived bile duct epithelium morbidity increasing worldwide disease difficult diagnose inchoate stage poor prognosis therefore clear understanding pathogenesis major influencing factors key develop effective therapeutic methods cca previous studies canonical correlation analysis demonstrated tumour microenvironment plays intricate role progression various types cancers including cca cca tumour microenvironment dynamic environment consisting authoritative tumour stromal cells extracellular matrix tumour stromal cells cancer cells thrive cca stromal cells include immune non immune cells inflammatory cells endothelial cells fibroblasts macrophages likewise cca tumour microenvironment contains abundant proliferative factors significantly impact behaviour cancer cells abominably intricate interactions cca cells cca tumour microenvironment plays important role promoting tumour proliferation accelerating neovascularization facilitating tumour invasion preventing tumour cells organismal immune reactions apoptosis review summarizes recent research progress regarding connection tumour behaviours tumour stromal cells cca well mechanism underlying effect tumour stromal cells growth cca thorough understanding relationship cca tumour stromal cells shed light development new therapeutic methods treating cca pubmed","probabilities":0.9799733,"Title":"The role of tumour microenvironment: a new vision for cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a relatively rare malignant and lethal tumour derived from bile duct epithelium and the morbidity is now increasing worldwide. This disease is difficult to diagnose at its inchoate stage and has poor prognosis. Therefore, a clear understanding of pathogenesis and major influencing factors is the key to develop effective therapeutic methods for CCA. In previous studies, canonical correlation analysis has demonstrated that tumour microenvironment plays an intricate role in the progression of various types of cancers including CCA. CCA tumour microenvironment is a dynamic environment consisting of authoritative tumour stromal cells and extracellular matrix where tumour stromal cells and cancer cells can thrive. CCA stromal cells include immune and non-immune cells, such as inflammatory cells, endothelial cells, fibroblasts, and macrophages. Likewise, CCA tumour microenvironment contains abundant proliferative factors and can significantly impact the behaviour of cancer cells. Through abominably intricate interactions with CCA cells, CCA tumour microenvironment plays an important role in promoting tumour proliferation, accelerating neovascularization, facilitating tumour invasion, and preventing tumour cells from organismal immune reactions and apoptosis. This review summarizes the recent research progress regarding the connection between tumour behaviours and tumour stromal cells in CCA, as well as the mechanism underlying the effect of tumour stromal cells on the growth of CCA. A thorough understanding of the relationship between CCA and tumour stromal cells can shed some light on the development of new therapeutic methods for treating CCA.","Source":"PubMed","category":"HUMAN","training_data":"The role of tumour microenvironment: a new vision for cholangiocarcinoma Cholangiocarcinoma (CCA) is a relatively rare malignant and lethal tumour derived from bile duct epithelium and the morbidity is now increasing worldwide. This disease is difficult to diagnose at its inchoate stage and has poor prognosis. Therefore, a clear understanding of pathogenesis and major influencing factors is the key to develop effective therapeutic methods for CCA. In previous studies, canonical correlation analysis has demonstrated that tumour microenvironment plays an intricate role in the progression of various types of cancers including CCA. CCA tumour microenvironment is a dynamic environment consisting of authoritative tumour stromal cells and extracellular matrix where tumour stromal cells and cancer cells can thrive. CCA stromal cells include immune and non-immune cells, such as inflammatory cells, endothelial cells, fibroblasts, and macrophages. Likewise, CCA tumour microenvironment contains abundant proliferative factors and can significantly impact the behaviour of cancer cells. Through abominably intricate interactions with CCA cells, CCA tumour microenvironment plays an important role in promoting tumour proliferation, accelerating neovascularization, facilitating tumour invasion, and preventing tumour cells from organismal immune reactions and apoptosis. This review summarizes the recent research progress regarding the connection between tumour behaviours and tumour stromal cells in CCA, as well as the mechanism underlying the effect of tumour stromal cells on the growth of CCA. A thorough understanding of the relationship between CCA and tumour stromal cells can shed some light on the development of new therapeutic methods for treating CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"biliary tract cancer incidence trends united states demographic group 1999 2013 background biliary tract cancers btcs rare deadly cancers gallbladder cancer gbc intrahepatic cholangiocarcinoma icc extrahepatic cholangiocarcinoma ecc ampulla vater cancer avc recent us study reported increasing gbc incidence among people younger 45 years blacks however examine trends biliary tract sites methods study characterized demographic differences btc incidence rates time trends anatomic site population based north american association central cancer registries data used calculate age adjusted incidence rates incidence rate ratios irrs estimated annual percent changes eapcs 1999 2013 site demographic group sites significant differences eapc age group irrs compared age group results gbc incidence rates declined among women eapc 0 5 y p 01 racial ethnic groups except non hispanic blacks among rates increased 1 8 y p 0001 although gbc rates increased among 18 44 year olds eapc 1 8 y p 01 decreased among people 45 years old older 0 4 y p 009 sex p 0001 racial ethnic differences p 003 02 gbc incidence larger younger people older people period icc eapc 3 2 y p 0001 ecc rates 1 8 y p 001 steadily increased across sex racial ethnic groups although avc incidence rates increased among younger adults eapc 1 8 y p 03 older adults 0 20 y p 30 sex racial ethnic irrs differ age conclusions differential patterns btc rates temporal trends identified anatomic site demographic groups findings highlight need large pooling projects evaluate btc risk factors anatomic site stn","probabilities":0.9799733,"Title":"Biliary Tract Cancer Incidence And Trends In The United States By Demographic Group 1999-2013","Abstract":"Background: Biliary tract cancers (BTCs) are rare but deadly cancers (gallbladder cancer [GBC], intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], and ampulla of Vater cancer [AVC]). A recent US study reported increasing GBC incidence among people younger than 45 years and blacks; however, it did not examine trends for other biliary tract sites. \r\n\r\n Methods: This study characterized demographic differences in BTC incidence rates and time trends by anatomic site. Population-based North American Association of Central Cancer Registries data were used to calculate age-adjusted incidence rates, incidence rate ratios (IRRs), and estimated annual percent changes (eAPCs) for 1999-2013 by site and demographic group. For sites with significant differences in eAPC by age group, IRRs were compared by age group. \r\n\r\n Results: GBC incidence rates declined among women (eAPC, -0.5%/y; P = .01) and all racial/ethnic groups except for non-Hispanic blacks, among whom rates increased (1.8%/y; P < .0001). Although GBC rates increased among 18- to 44-year-olds (eAPC, 1.8%/y; P = .01), they decreased among people 45 years old or older (-0.4%/y; P = .009). Sex (P < .0001) and racial/ethnic differences (P = .003 to .02) in GBC incidence were larger for younger people than older people. During this period, ICC (eAPC, 3.2%/y; P < .0001) and ECC rates (1.8%/y; P = .001) steadily increased across sex and racial/ethnic groups. Although AVC incidence rates increased among younger adults (eAPC, 1.8%/y; P = .03) but not older adults (-0.20%/y; P = .30), sex and racial/ethnic IRRs did not differ by age. \r\n\r\n Conclusions: Differential patterns of BTC rates and temporal trends have been identified by anatomic site and demographic groups. These findings highlight the need for large pooling projects to evaluate BTC risk factors by anatomic site.","Source":"STN","category":"HUMAN","training_data":"Biliary Tract Cancer Incidence And Trends In The United States By Demographic Group 1999-2013 Background: Biliary tract cancers (BTCs) are rare but deadly cancers (gallbladder cancer [GBC], intrahepatic cholangiocarcinoma [ICC], extrahepatic cholangiocarcinoma [ECC], and ampulla of Vater cancer [AVC]). A recent US study reported increasing GBC incidence among people younger than 45 years and blacks; however, it did not examine trends for other biliary tract sites. \r\n\r\n Methods: This study characterized demographic differences in BTC incidence rates and time trends by anatomic site. Population-based North American Association of Central Cancer Registries data were used to calculate age-adjusted incidence rates, incidence rate ratios (IRRs), and estimated annual percent changes (eAPCs) for 1999-2013 by site and demographic group. For sites with significant differences in eAPC by age group, IRRs were compared by age group. \r\n\r\n Results: GBC incidence rates declined among women (eAPC, -0.5%/y; P = .01) and all racial/ethnic groups except for non-Hispanic blacks, among whom rates increased (1.8%/y; P < .0001). Although GBC rates increased among 18- to 44-year-olds (eAPC, 1.8%/y; P = .01), they decreased among people 45 years old or older (-0.4%/y; P = .009). Sex (P < .0001) and racial/ethnic differences (P = .003 to .02) in GBC incidence were larger for younger people than older people. During this period, ICC (eAPC, 3.2%/y; P < .0001) and ECC rates (1.8%/y; P = .001) steadily increased across sex and racial/ethnic groups. Although AVC incidence rates increased among younger adults (eAPC, 1.8%/y; P = .03) but not older adults (-0.20%/y; P = .30), sex and racial/ethnic IRRs did not differ by age. \r\n\r\n Conclusions: Differential patterns of BTC rates and temporal trends have been identified by anatomic site and demographic groups. These findings highlight the need for large pooling projects to evaluate BTC risk factors by anatomic site. STN","prediction_labels":"HUMAN"},{"cleaned":"mboat7 rs641738 variant associated improved outcome primary sclerosing cholangitis background aims primary sclerosing cholangitis psc chronic cholestatic disease causes liver cirrhosis leading liver failure additionally psc risk factor cholangiocarcinoma mechanism unknown liver transplantation remains sole curative option membrane bound o acyltransferase domain containing 7 mboat7 rs641738 rs626283 variant alleles associated accelerated progression disease higher risk developing severe phenotype many chronic hepatic diseases thus analysed effect long term outcomes laboratory parameters psc patients methods determined mboat7 genotypes estimated actuarial survival rate free liver transplantation using kaplan meier estimator differences estimates analysed using log rank test patient blood drawn analysed different serum parameters including cholestatic markers additionally mboat7 rna expression human hepatic cell lines mzcha1 biliary adenocarcinoma cell line hepg2 hepatocellular carcinoma cell line lx 2 hepatic stellate cell line h 69 cholangiocyte cell line analysed results transplant free survival significantly prolonged carriers two rs641738 variant alleles referred tt genotype mean 19 6 years 95 confidence interval ci 16 3 22 9 years compared cc mean 15 4 years 95 ci 12 8 18 0 years heterozygous genotypes mean 13 2 years 95 ci 11 4 15 0 years p 0 017 effect restricted male patients confirmed high expression mboat7 hepatic stellate cells found mboat7 less expressed biliary epithelial cell lines compared parenchymal hepatic cells conclusions unlike chronic liver diseases carrying two mboat7 variant alleles seem affect psc patients negatively seems positive effect transplant free survival study help improve individual prognosis psc patients give new perspective involvement immune system psc stn","probabilities":0.9467213,"Title":"The Mboat7 Rs641738 Variant Is Associated With An Improved Outcome In Primary Sclerosing Cholangitis","Abstract":"Background and aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that causes liver cirrhosis, leading to liver failure. Additionally, PSC is a risk factor for cholangiocarcinoma. Its mechanism is unknown, and liver transplantation remains the sole curative option. The membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738 and rs626283 variant alleles have been associated with both an accelerated progression of the disease and a higher risk for developing a more severe phenotype in many chronic hepatic diseases. Thus, we analysed their effect on long-term outcomes and laboratory parameters in PSC patients. \n\n Methods: We determined MBOAT7 genotypes and estimated the actuarial survival rate free of liver transplantation, using the Kaplan-Meier estimator. The differences between the estimates were analysed using the log-rank test. Patient blood was drawn and analysed for different serum parameters including cholestatic markers. Additionally, MBOAT7 RNA expression in human hepatic cell lines MZCHA1 (a biliary adenocarcinoma cell line), HepG2 (a hepatocellular carcinoma cell line), LX-2 (hepatic stellate cell line) and H-69 (cholangiocyte cell line) was analysed. \n\n Results: Transplant-free survival was significantly prolonged in carriers of two rs641738 variant alleles, which was referred to as the TT genotype (mean 19.6 years; 95% confidence interval [CI]: 16.3-22.9 years) compared to the CC (mean 15.4 years, 95% CI 12.8-18.0 years) and heterozygous genotypes (mean 13.2 years, 95% CI 11.4-15.0 years) (P=0.017). This effect was restricted to male patients. We confirmed the high expression of MBOAT7 in hepatic stellate cells and found that MBOAT7 is less expressed in biliary epithelial cell lines, compared to parenchymal hepatic cells. \n\n Conclusions: Unlike other chronic liver diseases, carrying two MBOAT7 variant alleles does not seem to affect PSC patients negatively, but seems to have a positive effect on transplant-free survival. This study could help improve individual prognosis in PSC patients and give some new perspective on the involvement of the immune system in PSC.","Source":"STN","category":"ANIMAL","training_data":"The Mboat7 Rs641738 Variant Is Associated With An Improved Outcome In Primary Sclerosing Cholangitis Background and aims: Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease that causes liver cirrhosis, leading to liver failure. Additionally, PSC is a risk factor for cholangiocarcinoma. Its mechanism is unknown, and liver transplantation remains the sole curative option. The membrane bound O-acyltransferase domain containing 7 (MBOAT7) rs641738 and rs626283 variant alleles have been associated with both an accelerated progression of the disease and a higher risk for developing a more severe phenotype in many chronic hepatic diseases. Thus, we analysed their effect on long-term outcomes and laboratory parameters in PSC patients. \n\n Methods: We determined MBOAT7 genotypes and estimated the actuarial survival rate free of liver transplantation, using the Kaplan-Meier estimator. The differences between the estimates were analysed using the log-rank test. Patient blood was drawn and analysed for different serum parameters including cholestatic markers. Additionally, MBOAT7 RNA expression in human hepatic cell lines MZCHA1 (a biliary adenocarcinoma cell line), HepG2 (a hepatocellular carcinoma cell line), LX-2 (hepatic stellate cell line) and H-69 (cholangiocyte cell line) was analysed. \n\n Results: Transplant-free survival was significantly prolonged in carriers of two rs641738 variant alleles, which was referred to as the TT genotype (mean 19.6 years; 95% confidence interval [CI]: 16.3-22.9 years) compared to the CC (mean 15.4 years, 95% CI 12.8-18.0 years) and heterozygous genotypes (mean 13.2 years, 95% CI 11.4-15.0 years) (P=0.017). This effect was restricted to male patients. We confirmed the high expression of MBOAT7 in hepatic stellate cells and found that MBOAT7 is less expressed in biliary epithelial cell lines, compared to parenchymal hepatic cells. \n\n Conclusions: Unlike other chronic liver diseases, carrying two MBOAT7 variant alleles does not seem to affect PSC patients negatively, but seems to have a positive effect on transplant-free survival. This study could help improve individual prognosis in PSC patients and give some new perspective on the involvement of the immune system in PSC. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic factors survival curative resection distal cholangiocarcinoma perineural invasion lymphovascular invasion purpose purpose study elucidate prognostic factors distal cholangiocarcinoma curative resection assess significance perineural invasion pni lymphovascular invasion lvi prognostic factors methods retrospective analysis 91 patients underwent radical surgery distal cholangiocarcinoma march 2004 october 2011 performed analyzed survival rate prognostic factors affecting survival results overall 1 3 5 year survival rates 84 1 49 7 38 9 respectively univariate analysis prognostic factors influencing survival histological differentiation lymph node ln involvement tnm stage multivariate analysis ln metastasis independent prognostic factor although patients pni tended show poorer survival statistically significant factor 3 5 year os 62 0 54 6 vs 42 8 30 9 p 0 166 patients total lymph node count tlnc 11 less pni significant prognostic factor however significant factor patients tlnc 11 overall lvi influence patient survival conclusions ln metastasis significant prognostic factor curative resection distal cholangiocarcinoma cases adequate dissection performed appeared pni lvi influence survival pubmed","probabilities":0.9799733,"Title":"Prognostic factors for survival after curative resection of distal cholangiocarcinoma: perineural invasion and lymphovascular invasion","Abstract":"PURPOSE: The purpose of this study was to elucidate the prognostic factors for distal cholangiocarcinoma after curative resection, and to assess the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) as prognostic factors. METHODS: A retrospective analysis of 91 patients who underwent radical surgery for distal cholangiocarcinoma between March 2004 and October 2011 was performed. We analyzed the survival rate and prognostic factors affecting the survival. RESULTS: The overall 1-, 3- and 5-year survival rates were 84.1, 49.7 and 38.9 %, respectively. In the univariate analysis, the prognostic factors influencing the survival were the histological differentiation, lymph node (LN) involvement and TNM stage. In the multivariate analysis, LN metastasis was the only independent prognostic factor. Although patients with PNI tended to show poorer survival, it was not a statistically significant factor (3- and 5-year OS; 62.0 and 54.6 % vs. 42.8 and 30.9 %, P = 0.166). In the patients with a total lymph node count (TLNC) of 11 or less, PNI was a significant prognostic factor; however, it was not a significant factor in the patients with a TLNC over 11. Overall, the LVI had no influence on the patient survival. CONCLUSIONS: LN metastasis was the only significant prognostic factor after the curative resection of distal cholangiocarcinoma. In cases where adequate dissection was performed, it appeared that the PNI and LVI had no influence on the survival.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors for survival after curative resection of distal cholangiocarcinoma: perineural invasion and lymphovascular invasion PURPOSE: The purpose of this study was to elucidate the prognostic factors for distal cholangiocarcinoma after curative resection, and to assess the significance of perineural invasion (PNI) and lymphovascular invasion (LVI) as prognostic factors. METHODS: A retrospective analysis of 91 patients who underwent radical surgery for distal cholangiocarcinoma between March 2004 and October 2011 was performed. We analyzed the survival rate and prognostic factors affecting the survival. RESULTS: The overall 1-, 3- and 5-year survival rates were 84.1, 49.7 and 38.9 %, respectively. In the univariate analysis, the prognostic factors influencing the survival were the histological differentiation, lymph node (LN) involvement and TNM stage. In the multivariate analysis, LN metastasis was the only independent prognostic factor. Although patients with PNI tended to show poorer survival, it was not a statistically significant factor (3- and 5-year OS; 62.0 and 54.6 % vs. 42.8 and 30.9 %, P = 0.166). In the patients with a total lymph node count (TLNC) of 11 or less, PNI was a significant prognostic factor; however, it was not a significant factor in the patients with a TLNC over 11. Overall, the LVI had no influence on the patient survival. CONCLUSIONS: LN metastasis was the only significant prognostic factor after the curative resection of distal cholangiocarcinoma. In cases where adequate dissection was performed, it appeared that the PNI and LVI had no influence on the survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect ablative radiotherapy survival patients inoperable intrahepatic cholangiocarcinoma dose response analysis purpose standard therapies localized inoperable intrahepatic cholangiocarcinoma ihcc ineffective advances radiotherapy rt techniques image guidance enabled ablative doses delivered large liver tumors study evaluated effects rt dose escalation treatment ihcc patients methods seventy nine consecutive patients inoperable ihcc identified treated definitive rt 2002 2014 diagnosis median tumor size 7 9 cm range 2 2 17 cm seventy patients 89 received systemic chemotherapy rt rt doses 35 100 gy median 58 05 gy three 30 fractions median biologic equivalent dose bed 80 5 gy range 43 75 180 gy results median follow time patients alive time analysis 33 months range 11 93 months median overall survival os time diagnosis 30 months 3 year os rate 44 radiation dose single important prognostic factor higher doses correlated improved local control lc rate os 3 year os rate patients receiving bed greater 80 5 gy 73 versus 38 receiving lower doses p 017 3 year lc rate significantly higher 78 bed greater 80 5 gy lower doses 45 p 04 bed continuous variable significantly affected lc p 009 os p 004 significant treatment related toxicities conclusion delivery higher doses rt improves lc os inoperable ihcc bed greater 80 5 gy seems ablative dose rt large ihccs long term survival rates compare favorably resection stn","probabilities":0.9799733,"Title":"Effect Of Ablative Radiotherapy On Survival In Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Dose Response Analysis","Abstract":"Purpose: Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. \r\n\r\n Patients and methods: Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). \r\n\r\n Results: Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. \r\n\r\n Conclusion: Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection.","Source":"STN","category":"HUMAN","training_data":"Effect Of Ablative Radiotherapy On Survival In Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Dose Response Analysis Purpose: Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. \r\n\r\n Patients and methods: Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). \r\n\r\n Results: Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. \r\n\r\n Conclusion: Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection. STN","prediction_labels":"HUMAN"},{"cleaned":"correlation mmp1 par1 axis clinical outcome primary gallbladder carcinoma objective matrix metalloprotease 1 protease activated receptor 1 axis plays important role many cancers activation often associated poor survival aim present study determine whether immunohistochemical detection matrix metalloprotease 1 protease activated receptor 1 provide useful information novel therapeutic prognostic factors primary gallbladder carcinoma methods eighty six gallbladder carcinoma tissues evaluated immunohistochemistry matrix metalloprotease 1 protease activated receptor 1 expressions association matrix metalloprotease 1 protease activated receptor 1 expressions clinicopathological characteristics univariate survival analysis influence matrix metalloprotease 1 protease activated receptor 1 expressions overall survival analyzed results matrix metalloprotease 1 protease activated receptor 1 immunoreactivities observed 62 72 1 59 68 6 86 gallbladder carcinoma cases respectively tumors positive expressions matrix metalloprotease 1 p 0 007 protease activated receptor 1 p 0 01 frequently showed lymph node metastasis respectively addition tumors positive expressions matrix metalloprotease 1 protease activated receptor 1 tended show deeper invasion depth p 0 006 0 008 respectively frequent lymphovascular invasion p 0 01 kaplan meier survival curves demonstrated patients positive expressions matrix metalloprotease 1 protease activated receptor 1 significantly shorter survival time patients negative expression p 0 02 conclusions subset gallbladder carcinoma cases revealed overexpression matrix metalloprotease 1 protease activated receptor 1 associated progressive pathological feature aggressive clinical course therefore matrix metalloprotease 1 protease activated receptor 1 expressions may predictors poor prognosis patients gallbladder carcinoma first report describing involvement matrix metalloprotease 1 protease activated receptor 1 axis gallbladder carcinoma stn","probabilities":0.88235295,"Title":"Correlation Between Mmp1-Par1 Axis And Clinical Outcome Of Primary Gallbladder Carcinoma","Abstract":"Objective: Matrix metalloprotease-1 and protease-activated receptor-1 axis plays an important role in many cancers, with activation often associated with poor survival. The aim of the present study was to determine whether the immunohistochemical detection of matrix metalloprotease-1 and protease-activated receptor-1 could provide useful information as novel therapeutic or prognostic factors in primary gallbladder carcinoma. \r\n\r\n Methods: Eighty-six gallbladder carcinoma tissues were evaluated by immunohistochemistry for matrix metalloprotease-1 and protease-activated receptor-1 expressions. The association of matrix metalloprotease-1 and protease-activated receptor-1 expressions with clinicopathological characteristics and the univariate survival analysis for the influence of matrix metalloprotease-1 and protease-activated receptor-1 expressions on the overall survival were analyzed. \r\n\r\n Results: Matrix metalloprotease-1 and protease-activated receptor-1 immunoreactivities were observed in 62 (72.1%) and 59 (68.6%) of the 86 gallbladder carcinoma cases, respectively. The tumors with the positive expressions of matrix metalloprotease-1 (P= 0.007) and protease-activated receptor-1 (P= 0.01) more frequently showed lymph node metastasis, respectively. In addition, the tumors with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 tended to show a deeper invasion depth (P= 0.006 and 0.008, respectively) and more frequent lymphovascular invasion (both P= 0.01). The Kaplan-Meier survival curves demonstrated that patients with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 had a significantly shorter survival time than those patients with their negative expression (both P= 0.02). \r\n\r\n Conclusions: A subset of gallbladder carcinoma cases revealed the overexpression of matrix metalloprotease-1 and protease-activated receptor-1, which was associated with a progressive pathological feature and an aggressive clinical course. Therefore, matrix metalloprotease-1 and protease-activated receptor-1 expressions may be predictors for a poor prognosis in patients with gallbladder carcinoma. This is the first report describing about the involvement of matrix metalloprotease-1 and protease-activated receptor-1 axis in gallbladder carcinoma.","Source":"STN","category":"ANIMAL","training_data":"Correlation Between Mmp1-Par1 Axis And Clinical Outcome Of Primary Gallbladder Carcinoma Objective: Matrix metalloprotease-1 and protease-activated receptor-1 axis plays an important role in many cancers, with activation often associated with poor survival. The aim of the present study was to determine whether the immunohistochemical detection of matrix metalloprotease-1 and protease-activated receptor-1 could provide useful information as novel therapeutic or prognostic factors in primary gallbladder carcinoma. \r\n\r\n Methods: Eighty-six gallbladder carcinoma tissues were evaluated by immunohistochemistry for matrix metalloprotease-1 and protease-activated receptor-1 expressions. The association of matrix metalloprotease-1 and protease-activated receptor-1 expressions with clinicopathological characteristics and the univariate survival analysis for the influence of matrix metalloprotease-1 and protease-activated receptor-1 expressions on the overall survival were analyzed. \r\n\r\n Results: Matrix metalloprotease-1 and protease-activated receptor-1 immunoreactivities were observed in 62 (72.1%) and 59 (68.6%) of the 86 gallbladder carcinoma cases, respectively. The tumors with the positive expressions of matrix metalloprotease-1 (P= 0.007) and protease-activated receptor-1 (P= 0.01) more frequently showed lymph node metastasis, respectively. In addition, the tumors with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 tended to show a deeper invasion depth (P= 0.006 and 0.008, respectively) and more frequent lymphovascular invasion (both P= 0.01). The Kaplan-Meier survival curves demonstrated that patients with the positive expressions of matrix metalloprotease-1 and protease-activated receptor-1 had a significantly shorter survival time than those patients with their negative expression (both P= 0.02). \r\n\r\n Conclusions: A subset of gallbladder carcinoma cases revealed the overexpression of matrix metalloprotease-1 and protease-activated receptor-1, which was associated with a progressive pathological feature and an aggressive clinical course. Therefore, matrix metalloprotease-1 and protease-activated receptor-1 expressions may be predictors for a poor prognosis in patients with gallbladder carcinoma. This is the first report describing about the involvement of matrix metalloprotease-1 and protease-activated receptor-1 axis in gallbladder carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"albumin gamma glutamyltransferase ratio prognostic indicator intrahepatic cholangiocarcinoma curative resection prognosis intrahepatic cholangiocarcinoma icc remains poor whereas predictive models survival prediction icc patients following curative resection limited herein established novel inflammation based score derived preoperative albumin gamma glutamyltransferase ratio agr evaluated prognostic significance icc patients underwent curative resection prognostic value agr retrospectively studied cohort comprising 206 icc patients following curative resection predictive performance agr compared inflammation based scores serological tumor markers terms concordance index c index prognostic nomograms incorporating agr tumor node metastasis tnm staging systems established achieve better discriminatory ability optimal cut value agr 0 6 multivariate analysis showed agr independent predictor overall survival os p 0 003 recurrence free survival rfs p 0 046 c index agr superior inflammation based scores serological tumor markers os rfs prediction established nomograms showed improved predictive accuracy compared tnm staging systems alone results indicate agr independent prognostic indicator icc underwent curative resection incorporation agr existing tnm staging systems achieved improved predictive accuracy pubmed","probabilities":0.9799733,"Title":"Albumin to gamma-glutamyltransferase ratio as a prognostic indicator in intrahepatic cholangiocarcinoma after curative resection","Abstract":"The prognosis of intrahepatic cholangiocarcinoma (ICC) remains poor whereas predictive models for survival prediction in ICC patients following curative resection are limited. Herein, we established a novel inflammation-based score derived from preoperative albumin to gamma-glutamyltransferase ratio (AGR) and evaluated its prognostic significance in ICC patients underwent curative resection. Prognostic value of AGR was retrospectively studied in a cohort comprising 206 ICC patients following curative resection. The predictive performance of AGR was compared with other inflammation-based scores and serological tumor markers in terms of concordance index (C-index). Further, prognostic nomograms incorporating AGR into the tumor-node-metastasis (TNM) staging systems were established to achieve a better discriminatory ability. The optimal cut-off value of AGR was 0.6. Multivariate analysis showed that AGR was an independent predictor for overall survival (OS; P = 0.003) and recurrence-free survival (RFS; P = 0.046). The C-index of AGR was superior to other inflammation-based scores and serological tumor markers in OS and RFS prediction. The established nomograms showed improved predictive accuracy compared with the TNM staging systems alone. These results indicate that AGR is an independent prognostic indicator for ICC underwent curative resection. The incorporation of AGR into the existing TNM staging systems achieved improved predictive accuracy.","Source":"PubMed","category":"HUMAN","training_data":"Albumin to gamma-glutamyltransferase ratio as a prognostic indicator in intrahepatic cholangiocarcinoma after curative resection The prognosis of intrahepatic cholangiocarcinoma (ICC) remains poor whereas predictive models for survival prediction in ICC patients following curative resection are limited. Herein, we established a novel inflammation-based score derived from preoperative albumin to gamma-glutamyltransferase ratio (AGR) and evaluated its prognostic significance in ICC patients underwent curative resection. Prognostic value of AGR was retrospectively studied in a cohort comprising 206 ICC patients following curative resection. The predictive performance of AGR was compared with other inflammation-based scores and serological tumor markers in terms of concordance index (C-index). Further, prognostic nomograms incorporating AGR into the tumor-node-metastasis (TNM) staging systems were established to achieve a better discriminatory ability. The optimal cut-off value of AGR was 0.6. Multivariate analysis showed that AGR was an independent predictor for overall survival (OS; P = 0.003) and recurrence-free survival (RFS; P = 0.046). The C-index of AGR was superior to other inflammation-based scores and serological tumor markers in OS and RFS prediction. The established nomograms showed improved predictive accuracy compared with the TNM staging systems alone. These results indicate that AGR is an independent prognostic indicator for ICC underwent curative resection. The incorporation of AGR into the existing TNM staging systems achieved improved predictive accuracy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment outcomes gall bladder cancer 10 years experience introduction purpose gall bladder cancers even curative surgery survivals dismal loco regional failure accounts 40 86 although considered radio resistant adjuvant radiation without chemotherapy tried improve loco regional control overall survival rates aim evaluate natural history gall bladder cancers role radiation therapy rt prognostication retrospective analysis undertaken materials methods 1991 2000 60 patients gall bladder cancer treated radical intent evaluated patients details including history physical examination liver function tests ultrasonography abdomen chest x ray ct scan abdomen done noted patients underwent surgery surgical details histopathology pathological staging recorded details post operative adjuvant treatment including radiation therapy details well chemotherapeutic agents number cycles type infusion bolus infusion noted results sixty patients underwent surgery histopathological staging 28 patients 46 5 stage ii 19 32 stage iii 12 20 stage 1 patient stage iv disease thirteen 21 patents receive adjuvant treatment 32 53 patients received adjuvant rt alone 8 14 received post operative ct rt 7 12 patients received ct alone median follow 18 months 12 124 months 27 45 patients disease free 11 19 local failures 7 11 loco regional 7 11 loco regional distant 4 7 distant 4 7 patients local distant failures overall disease free survival dfs overall survival 30 25 5 years respectively stage grouping p 0 007 pathological p 0 01 significant impact dfs univariate analysis histological grade p 0 06 showed trend towards significance conclusion gall bladder cancers aggressive lethal early diagnosis curative surgery followed appropriate adjuvant radiation therapy may improve survivals established consensus till date following curative surgery pathological stage stage grouping significant prognostic factors outcome stn","probabilities":0.9799733,"Title":"Treatment Outcomes Of Gall Bladder Cancer 10 Years Experience","Abstract":"Introduction and purpose: In gall bladder cancers, even after curative surgery, survivals are dismal and loco-regional failure accounts for 40-86%. Although these are considered radio-resistant, adjuvant radiation, with or without chemotherapy, has been tried to improve loco-regional control and overall survival rates. With an aim to evaluate the natural history of gall bladder cancers, role of radiation therapy (RT) and prognostication, a retrospective analysis was undertaken. \n\n Materials and methods: Between 1991-2000, 60 patients with gall bladder cancer, treated with radical intent, were evaluated. Patients details including history, physical examination, liver function tests, ultrasonography of the abdomen and chest X-ray; and CT scan Abdomen if done, were noted. In patients who underwent surgery, surgical details, histopathology and pathological staging, were recorded. The details of post-operative adjuvant treatment, including radiation therapy details, as well as chemotherapeutic agents, number of cycles and type of infusion [bolus/infusion], were noted. \n\n Results: Sixty patients underwent surgery. On histopathological staging, 28 patients (46.5%) had stage II, 19 (32%) had stage III, 12 (20%) had stage-I and 1 patient had stage IV disease. Thirteen (21%) patents did not receive any adjuvant treatment, 32 (53%) patients received adjuvant RT alone, 8(14%) received post-operative CT+RT and 7 (12%) patients received CT alone. With a median follow-up of 18 months (12-124 months), 27 (45%) patients were disease free, 11 (19%) had local failures, 7 (11%) had loco-regional, 7 (11%) loco-regional+distant, 4 (7%) distant and 4 (7%) patients had local+distant failures. The Overall Disease Free Survival (DFS) and overall survival was 30% and 25%, at 5 years, respectively. Stage grouping ('P' = 0.007), Pathological T ('P' = 0.01) had significant impact on DFS on univariate analysis, where as histological grade ('P' = 0.06) showed trend towards significance. \n\n Conclusion: Gall bladder cancers are aggressive and lethal. Early diagnosis and curative surgery, followed by appropriate adjuvant radiation therapy, may improve survivals, with no established consensus till date. Following curative surgery, pathological T stage and stage grouping, are the significant prognostic factors for outcome.","Source":"STN","category":"HUMAN","training_data":"Treatment Outcomes Of Gall Bladder Cancer 10 Years Experience Introduction and purpose: In gall bladder cancers, even after curative surgery, survivals are dismal and loco-regional failure accounts for 40-86%. Although these are considered radio-resistant, adjuvant radiation, with or without chemotherapy, has been tried to improve loco-regional control and overall survival rates. With an aim to evaluate the natural history of gall bladder cancers, role of radiation therapy (RT) and prognostication, a retrospective analysis was undertaken. \n\n Materials and methods: Between 1991-2000, 60 patients with gall bladder cancer, treated with radical intent, were evaluated. Patients details including history, physical examination, liver function tests, ultrasonography of the abdomen and chest X-ray; and CT scan Abdomen if done, were noted. In patients who underwent surgery, surgical details, histopathology and pathological staging, were recorded. The details of post-operative adjuvant treatment, including radiation therapy details, as well as chemotherapeutic agents, number of cycles and type of infusion [bolus/infusion], were noted. \n\n Results: Sixty patients underwent surgery. On histopathological staging, 28 patients (46.5%) had stage II, 19 (32%) had stage III, 12 (20%) had stage-I and 1 patient had stage IV disease. Thirteen (21%) patents did not receive any adjuvant treatment, 32 (53%) patients received adjuvant RT alone, 8(14%) received post-operative CT+RT and 7 (12%) patients received CT alone. With a median follow-up of 18 months (12-124 months), 27 (45%) patients were disease free, 11 (19%) had local failures, 7 (11%) had loco-regional, 7 (11%) loco-regional+distant, 4 (7%) distant and 4 (7%) patients had local+distant failures. The Overall Disease Free Survival (DFS) and overall survival was 30% and 25%, at 5 years, respectively. Stage grouping ('P' = 0.007), Pathological T ('P' = 0.01) had significant impact on DFS on univariate analysis, where as histological grade ('P' = 0.06) showed trend towards significance. \n\n Conclusion: Gall bladder cancers are aggressive and lethal. Early diagnosis and curative surgery, followed by appropriate adjuvant radiation therapy, may improve survivals, with no established consensus till date. Following curative surgery, pathological T stage and stage grouping, are the significant prognostic factors for outcome. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance neutrophil prealbumin ratio intrahepatic cholangiocarcinoma undergoing curative resection background study aimed clarify prognostic significance neutrophil prealbumin ratio index npri overall survival os recurrence free survival rfs icc curative surgery methods two hundred seventy six icc patients underwent curative resection december 2006 april 2017 recruited analyzed retrospectively correlations clinicopathological features npri analyzed os rfs calculated using kaplan meier curve cox univariate multivariate analyses used identify prognostic factors results optimal cut value npri determined roc curve 1 74 patients divided high value low value groups high value npri associated higher risk postoperative complications p 0 035 longer hospitalization p 0 004 univariate multivariate cox analyses demonstrated npri independent predictor os p 0 015 rfs p 0 004 icc curative resection furthermore npri also significant predictor os rfs different subgroups icc including ca19 9 35u ml single tumor vascular invasion local invasion ajcc stages ii conclusions npri independent prognostic predictor icc curative resection high clinical values due convenience pubmed","probabilities":0.9799733,"Title":"Prognostic significance of neutrophil/prealbumin ratio for intrahepatic cholangiocarcinoma undergoing curative resection","Abstract":"BACKGROUND: This study aimed to clarify the prognostic significance of neutrophil/prealbumin ratio index (NPRI) for overall survival (OS) and recurrence free survival (RFS) of ICC after curative surgery. METHODS: Two-hundred and seventy-six ICC patients who underwent curative resection from December 2006 to April 2017 were recruited and analyzed retrospectively. The correlations between clinicopathological features and NPRI were analyzed. OS and RFS were calculated using Kaplan-Meier curve, and cox univariate and multivariate analyses were used to identify the prognostic factors. RESULTS: The optimal cut-off value of NPRI determined by ROC curve was 1.74 and the patients were divided into high-value and low-value groups. High-value NPRI was associated with higher risk of postoperative complications (p = 0.035) and longer hospitalization (p = 0.004).Univariate and multivariate cox analyses demonstrated that NPRI was an independent predictor for OS (p = 0.015) and RFS (p = 0.004) in ICC after curative resection. Furthermore, NPRI was also a significant predictor for OS and RFS in different subgroups of ICC, including CA19-9<35U/mL, single tumor, no vascular invasion, no local invasion and AJCC stages I + II. CONCLUSIONS: NPRI was an independent prognostic predictor for ICC after curative resection. It would have high clinical values due to its convenience.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of neutrophil/prealbumin ratio for intrahepatic cholangiocarcinoma undergoing curative resection BACKGROUND: This study aimed to clarify the prognostic significance of neutrophil/prealbumin ratio index (NPRI) for overall survival (OS) and recurrence free survival (RFS) of ICC after curative surgery. METHODS: Two-hundred and seventy-six ICC patients who underwent curative resection from December 2006 to April 2017 were recruited and analyzed retrospectively. The correlations between clinicopathological features and NPRI were analyzed. OS and RFS were calculated using Kaplan-Meier curve, and cox univariate and multivariate analyses were used to identify the prognostic factors. RESULTS: The optimal cut-off value of NPRI determined by ROC curve was 1.74 and the patients were divided into high-value and low-value groups. High-value NPRI was associated with higher risk of postoperative complications (p = 0.035) and longer hospitalization (p = 0.004).Univariate and multivariate cox analyses demonstrated that NPRI was an independent predictor for OS (p = 0.015) and RFS (p = 0.004) in ICC after curative resection. Furthermore, NPRI was also a significant predictor for OS and RFS in different subgroups of ICC, including CA19-9<35U/mL, single tumor, no vascular invasion, no local invasion and AJCC stages I + II. CONCLUSIONS: NPRI was an independent prognostic predictor for ICC after curative resection. It would have high clinical values due to its convenience. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma definition intrahepatic malignant tumour composed cells resembling bile ducts intrahepatic peripheral cholangiocarcinoma icc arises portion intrahepatic bile duct epithelium e intrahepatic large bile ducts segmental area ducts finer branches intrahepatic small bile ducts cholangiocarcinoma arising right left hepatic ducts near junction called hilar cholangiocarcinoma considered extrahepatic lesion epidemiology incidence geographical distribution icc relatively rare tumour populations second among primary malignant liver tumours 15 liver cancers estimated icc 61 2162 1467 frequency icc among liver cancers ranges 5 males 12 females osaka japan 90 males 94 females khon kaen thailand 1467 1471 fig 8 29 highest incidence icc found areas laos north northeast thailand suffering endemic infection liver fluke opisthorchis viverrini 1997 age standardized incidence icc khon kaen thailand 88 per 100 000 males 37 105 females 1467 1471 90 histologically confirmed cases liver cancer khon kaen icc almost icc cases found related chronic o viverrini infection 2006 2007 clonorchis sinensis endemic area korea also high incidence liver cancer truncate incidence rates 35 64 years group 75 per 100 000 males 16 per 100 000 females 23 20 liver cancers pusan korea icc 871 time trends endemic non endemic areas significant changes incidence icc recent years 61 less 10 years since o viverrini drug therapy initiated since probably takes 30 years icc complicate opisthorchiasis trends icc probably likely change next decade 2007 2009 age sex distribution patients icc elderly clear sex differences icc occurs rather older ages hepatocellular carcinoma hcc clinical series 1419 google scholar","probabilities":0.9799733,"Title":"Intrahepatic Cholangiocarcinoma","Abstract":"Definition An intrahepatic malignant tumour composed of cells resembling those of bile ducts. Intrahepatic (or peripheral) cholangiocarcinoma (ICC) arises from any portion of the intrahepatic bile duct epithelium, i.e. from intrahepatic large bile ducts (the segmental and area ducts and their finer branches) or intrahepatic small bile ducts. Cholangiocarcinoma arising from the right and left hepatic ducts at or near their junction is called hilar cholangiocarcinoma and is considered an extrahepatic lesion.\nEpidemiology Incidence and geographical distribution ICC is a relatively rare tumour in most populations but second among primary malignant liver tumours; about 15% of liver cancers are estimated to be ICC {61, 2162, 1467}. The frequency of ICC among all liver cancers ranges from 5% in males and 12% in females in Osaka, Japan, to 90% in males and 94% in females in Khon Kaen, Thailand {1467, 1471} (Fig. 8.29). The highest incidence of ICC is found in areas of Laos and North and Northeast Thailand suffering from endemic infection with the liver fluke, Opisthorchis viverrini . In 1997, the age standardized incidence of ICC in Khon Kaen (Thailand) was 88 per 100,000 in males and 37/105 in females {1467, 1471}. About 90% of the histologically confirmed cases of liver cancer in Khon Kaen are ICC, and almost all the ICC cases were found to be related to chronic O. viverrini infection {2006, 2007}. In the Clonorchis sinensis endemic area in Korea, there is also a high incidence of liver cancer with truncate incidence rates (35-64 years group) of 75 per 100,000 in males and 16 per 100,000 in females {23}. About 20% of liver cancers in Pusan, Korea, are ICC {871}.\nTime trends In both endemic and non-endemic areas, there have been no significant changes in the incidence of ICC in recent years {61}. It is less than 10 years since O. viverrini drug therapy was initiated; since it probably takes 30 years for ICC to complicate opisthorchiasis, the trends of ICC are probably not likely to change in the next decade {2007, 2009}.\nAge and sex distribution Patients with ICC are elderly, with no clear sex differences. ICC occurs at rather older ages than hepatocellular carcinoma (HCC) in most clinical series {1419}.","Source":"Google Scholar","category":"HUMAN","training_data":"Intrahepatic Cholangiocarcinoma Definition An intrahepatic malignant tumour composed of cells resembling those of bile ducts. Intrahepatic (or peripheral) cholangiocarcinoma (ICC) arises from any portion of the intrahepatic bile duct epithelium, i.e. from intrahepatic large bile ducts (the segmental and area ducts and their finer branches) or intrahepatic small bile ducts. Cholangiocarcinoma arising from the right and left hepatic ducts at or near their junction is called hilar cholangiocarcinoma and is considered an extrahepatic lesion.\nEpidemiology Incidence and geographical distribution ICC is a relatively rare tumour in most populations but second among primary malignant liver tumours; about 15% of liver cancers are estimated to be ICC {61, 2162, 1467}. The frequency of ICC among all liver cancers ranges from 5% in males and 12% in females in Osaka, Japan, to 90% in males and 94% in females in Khon Kaen, Thailand {1467, 1471} (Fig. 8.29). The highest incidence of ICC is found in areas of Laos and North and Northeast Thailand suffering from endemic infection with the liver fluke, Opisthorchis viverrini . In 1997, the age standardized incidence of ICC in Khon Kaen (Thailand) was 88 per 100,000 in males and 37/105 in females {1467, 1471}. About 90% of the histologically confirmed cases of liver cancer in Khon Kaen are ICC, and almost all the ICC cases were found to be related to chronic O. viverrini infection {2006, 2007}. In the Clonorchis sinensis endemic area in Korea, there is also a high incidence of liver cancer with truncate incidence rates (35-64 years group) of 75 per 100,000 in males and 16 per 100,000 in females {23}. About 20% of liver cancers in Pusan, Korea, are ICC {871}.\nTime trends In both endemic and non-endemic areas, there have been no significant changes in the incidence of ICC in recent years {61}. It is less than 10 years since O. viverrini drug therapy was initiated; since it probably takes 30 years for ICC to complicate opisthorchiasis, the trends of ICC are probably not likely to change in the next decade {2007, 2009}.\nAge and sex distribution Patients with ICC are elderly, with no clear sex differences. ICC occurs at rather older ages than hepatocellular carcinoma (HCC) in most clinical series {1419}. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"impact prior cancer history overall survival patients newly diagnosed cancer pan cancer analysis seer database population cancer survivors prior cancer rapidly growing whether prior cancer diagnosis interferes outcome unknown conducted pan cancer analysis determine impact prior cancer history patients newly diagnosed cancer identified 20 types primary solid tumors 2004 2008 surveillance epidemiology end results database demographic clinicopathologic variables compared 2 test test appropriate propensity score adjusted kaplan meier method cox proportional hazards models used evaluate impact prior cancer overall survival os among 1 557 663 eligible patients 261 474 16 79 history prior cancer 65 prior cancers diagnosed within 5 years classified 20 cancer sites two groups pci pcs according different impacts prior cancer os pci patients prior cancer history involved colon rectum bone soft tissues melanoma breast cervix uteri corpus uterus prostate urinary bladder kidney renal pelvis eye orbits thyroid inferior os pcs patients nasopharynx esophagus stomach liver gallbladder pancreas lung ovary brain prior cancer history showed similar os patients without prior cancer pan cancer study presents landscape survival impact prior cancer across 20 cancer types compared patients without prior cancer pci group inferior os pcs group similar os studies still needed pubmed","probabilities":0.88235295,"Title":"Impact of prior cancer history on the overall survival of patients newly diagnosed with cancer: A pan-cancer analysis of the SEER database","Abstract":"The population of cancer survivors with prior cancer is rapidly growing. Whether a prior cancer diagnosis interferes with outcome is unknown. We conducted a pan-cancer analysis to determine the impact of prior cancer history for patients newly diagnosed with cancer. We identified 20 types of primary solid tumors between 2004 and 2008 in the Surveillance, Epidemiology, and End Results database. Demographic and clinicopathologic variables were compared by χ(2) test and t-test as appropriate. The propensity score-adjusted Kaplan-Meier method and Cox proportional hazards models were used to evaluate the impact of prior cancer on overall survival (OS). Among 1,557,663 eligible patients, 261,474 (16.79%) had a history of prior cancer. More than 65% of prior cancers were diagnosed within 5 years. We classified 20 cancer sites into two groups (PCI and PCS) according to the different impacts of prior cancer on OS. PCI patients with a prior cancer history, which involved the colon and rectum, bone and soft tissues, melanoma, breast, cervix uteri, corpus and uterus, prostate, urinary bladder, kidney and renal pelvis, eye and orbits, thyroid, had inferior OS. The PCS patients (nasopharynx, esophagus, stomach, liver, gallbladder, pancreas, lung, ovary and brain) with a prior cancer history showed similar OS to that of patients without prior cancer. Our pan-cancer study presents the landscape for the survival impact of prior cancer across 20 cancer types. Compared to the patients without prior cancer, the PCI group had inferior OS, while the PCS group had similar OS. Further studies are still needed.","Source":"PubMed","category":"HUMAN","training_data":"Impact of prior cancer history on the overall survival of patients newly diagnosed with cancer: A pan-cancer analysis of the SEER database The population of cancer survivors with prior cancer is rapidly growing. Whether a prior cancer diagnosis interferes with outcome is unknown. We conducted a pan-cancer analysis to determine the impact of prior cancer history for patients newly diagnosed with cancer. We identified 20 types of primary solid tumors between 2004 and 2008 in the Surveillance, Epidemiology, and End Results database. Demographic and clinicopathologic variables were compared by χ(2) test and t-test as appropriate. The propensity score-adjusted Kaplan-Meier method and Cox proportional hazards models were used to evaluate the impact of prior cancer on overall survival (OS). Among 1,557,663 eligible patients, 261,474 (16.79%) had a history of prior cancer. More than 65% of prior cancers were diagnosed within 5 years. We classified 20 cancer sites into two groups (PCI and PCS) according to the different impacts of prior cancer on OS. PCI patients with a prior cancer history, which involved the colon and rectum, bone and soft tissues, melanoma, breast, cervix uteri, corpus and uterus, prostate, urinary bladder, kidney and renal pelvis, eye and orbits, thyroid, had inferior OS. The PCS patients (nasopharynx, esophagus, stomach, liver, gallbladder, pancreas, lung, ovary and brain) with a prior cancer history showed similar OS to that of patients without prior cancer. Our pan-cancer study presents the landscape for the survival impact of prior cancer across 20 cancer types. Compared to the patients without prior cancer, the PCI group had inferior OS, while the PCS group had similar OS. Further studies are still needed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"nerve growth factor expression associated perineural invasion extrahepatic cholangiocarcinoma background although presence perineural invasion recognized poor prognostic factor extrahepatic cholangiocarcinoma molecular mechanisms perineural invasion extrahepatic cholangiocarcinoma remain unclear nerve growth factor reported candidate predictive biomarker perineural invasion cancers aim investigate impact intratumoral nerve growth factor expression resected extrahepatic cholangiocarcinoma survival methods intratumoral nerve growth factor expression investigated immunohistochemically 112 patients resected extrahepatic cholangiocarcinoma associations nerve growth factor expression clinicopathological factors statistically evaluated risk factors poor survival analyzed using univariate multivariate analyses results high low nerve growth factor expression observed 62 55 50 45 patients respectively 112 patients significant correlation found nerve growth factor expression presence perineural invasion p 0 942 moreover nerve growth factor expression associated recurrence free survival p 0 861 overall survival p 0 973 multivariate analysis lymph node metastasis p 0 004 identified independent risk factor early recurrence presence perineural invasion p 0 002 lymph node metastasis p 0 001 identified independent risk factors poor survival conclusions intratumoral nerve growth factor expression associated perineural invasion recurrence free overall survival patients resected extrahepatic cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Nerve Growth Factor Expression Is Not Associated with Perineural Invasion in Extrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers. AIM: To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival. METHODS: Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses. RESULTS: High and low nerve growth factor expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P < 0.001) was identified as independent risk factors for poor survival. CONCLUSIONS: Intratumoral nerve growth factor expression is not associated with perineural invasion or recurrence-free and overall survival in patients with resected extrahepatic cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Nerve Growth Factor Expression Is Not Associated with Perineural Invasion in Extrahepatic Cholangiocarcinoma BACKGROUND: Although the presence of perineural invasion has been recognized as a poor prognostic factor in extrahepatic cholangiocarcinoma, the molecular mechanisms of perineural invasion in extrahepatic cholangiocarcinoma remain unclear. Nerve growth factor has been reported to be a candidate predictive biomarker of perineural invasion in some cancers. AIM: To investigate the impact of intratumoral nerve growth factor expression in resected extrahepatic cholangiocarcinoma on survival. METHODS: Intratumoral nerve growth factor expression was investigated immunohistochemically in 112 patients with resected extrahepatic cholangiocarcinoma. Associations between nerve growth factor expression and clinicopathological factors were statistically evaluated, and risk factors for poor survival were analyzed using univariate and multivariate analyses. RESULTS: High and low nerve growth factor expression was observed in 62 (55%) and 50 (45%) patients, respectively. For all 112 patients, no significant correlation was found between nerve growth factor expression and presence of perineural invasion (P = 0.942). Moreover, nerve growth factor expression was not associated with recurrence-free survival (P = 0.861) and overall survival (P = 0.973). In multivariate analysis, lymph node metastasis (P = 0.004) was identified as an independent risk factor for early recurrence and the presence of perineural invasion (P = 0.002) and lymph node metastasis (P < 0.001) was identified as independent risk factors for poor survival. CONCLUSIONS: Intratumoral nerve growth factor expression is not associated with perineural invasion or recurrence-free and overall survival in patients with resected extrahepatic cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prevalence clinical significance biliary intraepithelial neoplasia bilin cholangiocarcinoma biliary intraepithelial neoplasia bilin common noninvasive precursor lesion progresses cholangiocarcinoma cc often found synchronously adjacent tumor surgical resection margin aim study elucidate prevalence prognostic effect bilin survival resection cc retrospectively analyzed database patients cc underwent surgery performed institution 2010 2017 142 patients underwent surgery cc bilin detected 42 patients 29 5 univariate analysis extrahepatic cc extrah cc patients bilin lesions significantly showed better disease free survival p 0 05 also although statistically significant extrah cc patients bilin lesions revealed better overall survival os p 0 09 multivariate analysis presence bilin lesion irrespective location significantly associated better disease free survival hr 2 059 95 confidence interval ci 1 057 4 432 p 0 041 os hr 1 831 95 ci 1 149 3 534 p 0 044 extrah cc patients presence bilin lesions uncommon cc patients significantly associated better disease free survival os extrah cc patients however larger studies longer follow needed accurately determine clinical significance pubmed","probabilities":0.9799733,"Title":"Prevalence and Clinical Significance of Biliary Intraepithelial Neoplasia (BilIN) in Cholangiocarcinoma","Abstract":"Biliary intraepithelial neoplasia (BilIN) is the most common noninvasive precursor lesion which progresses to cholangiocarcinoma (CC) and is often found synchronously adjacent to the tumor or at the surgical resection margin. The aim of this study was to elucidate the prevalence and prognostic effect of BilIN on survival after resection for CC. We retrospectively analyzed the database of patients with CC who underwent surgery performed at our institution from 2010 to 2017. There were 142 patients who underwent surgery for CC. BilIN was detected in 42 patients (29.5%). On univariate analysis, extrahepatic CC (ExtraH CC) patients with BilIN lesions significantly showed better disease-free survival (P = 0.05). Also, although not statistically significant, ExtraH CC patients with BilIN lesions revealed better overall survival (OS) (P = 0.09). On multivariate analysis, presence of BilIN lesion, irrespective of location, was significantly associated with better disease-free survival (HR = 2.059, 95% confidence interval (CI): 1.057-4.432, P = 0.041) and OS (HR = 1.831, 95% CI: 1.149-3.534, P = 0.044) in ExtraH CC patients. The presence of BilIN lesions was not uncommon in CC patients and was significantly associated with better disease-free survival and OS in ExtraH CC patients. However, larger studies with longer follow-up are needed to accurately determine its clinical significance.","Source":"PubMed","category":"HUMAN","training_data":"Prevalence and Clinical Significance of Biliary Intraepithelial Neoplasia (BilIN) in Cholangiocarcinoma Biliary intraepithelial neoplasia (BilIN) is the most common noninvasive precursor lesion which progresses to cholangiocarcinoma (CC) and is often found synchronously adjacent to the tumor or at the surgical resection margin. The aim of this study was to elucidate the prevalence and prognostic effect of BilIN on survival after resection for CC. We retrospectively analyzed the database of patients with CC who underwent surgery performed at our institution from 2010 to 2017. There were 142 patients who underwent surgery for CC. BilIN was detected in 42 patients (29.5%). On univariate analysis, extrahepatic CC (ExtraH CC) patients with BilIN lesions significantly showed better disease-free survival (P = 0.05). Also, although not statistically significant, ExtraH CC patients with BilIN lesions revealed better overall survival (OS) (P = 0.09). On multivariate analysis, presence of BilIN lesion, irrespective of location, was significantly associated with better disease-free survival (HR = 2.059, 95% confidence interval (CI): 1.057-4.432, P = 0.041) and OS (HR = 1.831, 95% CI: 1.149-3.534, P = 0.044) in ExtraH CC patients. The presence of BilIN lesions was not uncommon in CC patients and was significantly associated with better disease-free survival and OS in ExtraH CC patients. However, larger studies with longer follow-up are needed to accurately determine its clinical significance. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance neutrophil lymphocyte ratio oncologic outcomes cholangiocarcinoma meta analysis increasing evidence indicates neutrophil lymphocyte ratio nlr useful biomarker long term outcomes patients cholangiocarcinoma however prognostic role nlr patients cholangiocarcinoma remains unclear thus current meta analysis undertaken clarify correlation nlr overall survival os cholangiocarcinoma comprehensive literature research conducted understand association nlr prognosis cholangiocarcinoma hazard ratio hr 95 confidence interval ci used assess os synthesized hr 1 449 95 ci 1 296 1 619 p 0 001 indicated high nlr unfavourable effect os overall meta analysis suggested elevated preoperative nlr associated poorer rates survival cholangiocarcinoma patients pubmed","probabilities":0.9799733,"Title":"Prognostic Significance of Neutrophil to Lymphocyte Ratio in Oncologic Outcomes of Cholangiocarcinoma: A Meta-analysis","Abstract":"Increasing evidence indicates that the neutrophil to lymphocyte ratio (NLR) is a useful biomarker of long-term outcomes in patients with cholangiocarcinoma. However, the prognostic role of NLR in patients with cholangiocarcinoma remains unclear. Thus, the current meta-analysis was undertaken to clarify the correlation between NLR and overall survival (OS) in cholangiocarcinoma, and a comprehensive literature research was conducted to understand the association of NLR and prognosis of cholangiocarcinoma. The hazard ratio (HR) with 95% confidence interval (CI) was used to assess OS. The synthesized HR of 1.449 (95% CI: 1.296-1.619, P < 0.001) indicated that a high NLR had an unfavourable effect on OS. Overall, this meta-analysis suggested that elevated preoperative NLR is associated with poorer rates of survival in cholangiocarcinoma patients.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Significance of Neutrophil to Lymphocyte Ratio in Oncologic Outcomes of Cholangiocarcinoma: A Meta-analysis Increasing evidence indicates that the neutrophil to lymphocyte ratio (NLR) is a useful biomarker of long-term outcomes in patients with cholangiocarcinoma. However, the prognostic role of NLR in patients with cholangiocarcinoma remains unclear. Thus, the current meta-analysis was undertaken to clarify the correlation between NLR and overall survival (OS) in cholangiocarcinoma, and a comprehensive literature research was conducted to understand the association of NLR and prognosis of cholangiocarcinoma. The hazard ratio (HR) with 95% confidence interval (CI) was used to assess OS. The synthesized HR of 1.449 (95% CI: 1.296-1.619, P < 0.001) indicated that a high NLR had an unfavourable effect on OS. Overall, this meta-analysis suggested that elevated preoperative NLR is associated with poorer rates of survival in cholangiocarcinoma patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association stem cell marker expression pattern survival human biliary tract cancer aim study investigate molecular protein expression pattern markers stemness phenotype clinicopathological significance human biliary tract cancer btc human btc cell lines cclp 1 egi 1 mzcha 1 mzcha 2 skcha 1 tfk 1 gbc analyzed vitro xenotransplanted animals expression markers stemness compared tissue microarrays tma 34 cases human btc complete pathomorphological clinical data survival molecular analyses mrna protein level included makers stemness progenitor bmi 1 sox 2 nestin cd133 cd44 nanog proliferation differentiation cell cycle proteins intermediate filaments investigated btc samples showed low moderate partially significantly different expression pattern stem cell markers vitro vivo tma hierarchical cluster analysis identified subgroups homogenous expression stem cell markers significantly differing respect cytokeratin expression xenografts ki67 proliferation marker human tma respectively thus indicating possible heterogeneous carcinogenesis pathways btc additionally stem cell markers linked morphology molecular markers proliferation differentiation mrna protein level finally survival analysis identified combination cd133 cd44 independent prognostic factor yet value prognostic factors need testing prospective study design stn","probabilities":0.9467213,"Title":"Association Of Stem Cell Marker Expression Pattern And Survival In Human Biliary Tract Cancer","Abstract":"The aim of this study was to investigate the molecular and protein expression pattern of markers of stemness phenotype and its clinicopathological significance in human biliary tract cancer (BTC). Human BTC cell lines (CCLP-1, Egi-1, MzChA-1, MzChA-2, SkChA-1, TFK-1 and GBC) were analyzed in vitro and in xenotransplanted animals for expression of markers of stemness and compared to tissue microarrays (TMA) of 34 cases of human BTC with complete pathomorphological and clinical data (survival). Molecular analyses on the mRNA and protein level included makers of stemness and progenitor (Bmi-1, Sox-2, Nestin, CD133, CD44 and Nanog), proliferation and differentiation (cell cycle proteins, intermediate filaments). The investigated BTC samples showed a low to moderate and partially significantly different expression pattern of the stem cell markers in vitro, in vivo and in TMA. Hierarchical cluster analysis identified subgroups with homogenous expression of stem cell markers significantly differing with respect to cytokeratin expression in xenografts and Ki67 proliferation marker in human TMA, respectively - thus indicating possible heterogeneous carcinogenesis pathways in BTC. Additionally, these stem cell markers could be linked to morphology and molecular markers of proliferation and differentiation on the mRNA and protein level. Finally, survival analysis identified the combination of CD133 and CD44 as an independent prognostic factor yet their value as prognostic factors need testing in prospective study design.","Source":"STN","category":"ANIMAL","training_data":"Association Of Stem Cell Marker Expression Pattern And Survival In Human Biliary Tract Cancer The aim of this study was to investigate the molecular and protein expression pattern of markers of stemness phenotype and its clinicopathological significance in human biliary tract cancer (BTC). Human BTC cell lines (CCLP-1, Egi-1, MzChA-1, MzChA-2, SkChA-1, TFK-1 and GBC) were analyzed in vitro and in xenotransplanted animals for expression of markers of stemness and compared to tissue microarrays (TMA) of 34 cases of human BTC with complete pathomorphological and clinical data (survival). Molecular analyses on the mRNA and protein level included makers of stemness and progenitor (Bmi-1, Sox-2, Nestin, CD133, CD44 and Nanog), proliferation and differentiation (cell cycle proteins, intermediate filaments). The investigated BTC samples showed a low to moderate and partially significantly different expression pattern of the stem cell markers in vitro, in vivo and in TMA. Hierarchical cluster analysis identified subgroups with homogenous expression of stem cell markers significantly differing with respect to cytokeratin expression in xenografts and Ki67 proliferation marker in human TMA, respectively - thus indicating possible heterogeneous carcinogenesis pathways in BTC. Additionally, these stem cell markers could be linked to morphology and molecular markers of proliferation and differentiation on the mRNA and protein level. Finally, survival analysis identified the combination of CD133 and CD44 as an independent prognostic factor yet their value as prognostic factors need testing in prospective study design. STN","prediction_labels":"ANIMAL"},{"cleaned":"cholangiocyte senescence caused lysophosphatidylcholine potential implication carcinogenesis background incidence biliary tract cancer patients pancreaticobiliary maljunction intrahepatic cholelithiasis markedly high undefined mechanism diseases biliary lysophosphatidylcholine lpc level reportedly increased study investigated influence lpc cholangiocytes focusing cellular senescence potential contribution carcinogenesis methods cultured mmnk 1 immortalized human cholangiocyte treated lpc vitro effect evaluated results lysophosphatidylcholine demonstrated cytotoxicity generation intracellular reactive oxygen species accordingly lpc provoked oxidative dna injury whereas gene expressions dna repair enzyme ogg1 mutyh mth1 remained unchanged interestingly lpc caused global dna hypomethylation frequently observed cancer tissues microarray analysis identified differentially regulated genes response lpc included components senescence associated secretory phenotype sasp including interleukin 8 il 8 il 6 transforming growth factor plasminogen activator inhibitor 1 significant induction genes confirmed quantitative real time polymerase chain reaction addition upregulation p21 gene expression senescence associated beta galactosidase activity widely used marker cellular senescence significantly induced treatment lpc conclusions based data cholangiocyte senescence sasp caused lpc potential pathogenic mechanisms development biliary tract cancer stn","probabilities":1.0,"Title":"Cholangiocyte Senescence Caused By Lysophosphatidylcholine As A Potential Implication In Carcinogenesis","Abstract":"Background: The incidence of biliary tract cancer in patients with pancreaticobiliary maljunction or intrahepatic cholelithiasis is markedly high with undefined mechanism. In these diseases, biliary lysophosphatidylcholine (LPC) level is reportedly increased. This study investigated the influence of LPC on cholangiocytes focusing on cellular senescence and its potential contribution to carcinogenesis. \r\n\r\n Methods: Cultured MMNK-1, an immortalized human cholangiocyte was treated with LPC in vitro and its effect was evaluated. \r\n\r\n Results: Lysophosphatidylcholine demonstrated cytotoxicity with generation of intracellular reactive oxygen species. Accordingly, LPC provoked oxidative DNA injury, whereas the gene expressions of DNA repair enzyme (OGG1, MUTYH, MTH1) remained unchanged. Interestingly, LPC caused global DNA hypomethylation, which is frequently observed in cancer tissues. Microarray analysis identified differentially regulated genes in response to LPC, which included the components of senescence-associated secretory phenotype (SASP) including interleukin-8 (IL-8), IL-6, transforming growth factor-β and plasminogen activator inhibitor-1. Significant induction of these genes was further confirmed by quantitative real-time polymerase chain reaction. In addition to upregulation of p21 gene expression, senescence-associated beta-galactosidase activity, a widely used marker of cellular senescence was significantly induced by the treatment of LPC. \r\n\r\n Conclusions: Based on these data, cholangiocyte senescence and SASP caused by LPC are potential pathogenic mechanisms in the development of biliary tract cancer.","Source":"STN","category":"ANIMAL","training_data":"Cholangiocyte Senescence Caused By Lysophosphatidylcholine As A Potential Implication In Carcinogenesis Background: The incidence of biliary tract cancer in patients with pancreaticobiliary maljunction or intrahepatic cholelithiasis is markedly high with undefined mechanism. In these diseases, biliary lysophosphatidylcholine (LPC) level is reportedly increased. This study investigated the influence of LPC on cholangiocytes focusing on cellular senescence and its potential contribution to carcinogenesis. \r\n\r\n Methods: Cultured MMNK-1, an immortalized human cholangiocyte was treated with LPC in vitro and its effect was evaluated. \r\n\r\n Results: Lysophosphatidylcholine demonstrated cytotoxicity with generation of intracellular reactive oxygen species. Accordingly, LPC provoked oxidative DNA injury, whereas the gene expressions of DNA repair enzyme (OGG1, MUTYH, MTH1) remained unchanged. Interestingly, LPC caused global DNA hypomethylation, which is frequently observed in cancer tissues. Microarray analysis identified differentially regulated genes in response to LPC, which included the components of senescence-associated secretory phenotype (SASP) including interleukin-8 (IL-8), IL-6, transforming growth factor-β and plasminogen activator inhibitor-1. Significant induction of these genes was further confirmed by quantitative real-time polymerase chain reaction. In addition to upregulation of p21 gene expression, senescence-associated beta-galactosidase activity, a widely used marker of cellular senescence was significantly induced by the treatment of LPC. \r\n\r\n Conclusions: Based on these data, cholangiocyte senescence and SASP caused by LPC are potential pathogenic mechanisms in the development of biliary tract cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"incidence cancer among grand multiparous women finland special focus non gynaecological cancers population based cohort study background many studies previously revealed evidence association grand multiparity five deliveries gynaecological cancer oestrogen impact cancer formation amount circulating oestrogen significantly higher pregnancy also lifestyle grand multiparous women differs somewhat average population considering factors plausible also non gynaecological cancers associated multiparity aim study determine cancer incidence among grand multiparous women special attention non gynaecological cancers material methods 102 541 women alive 1974 2011 least five deliveries identified finnish population register followed cancer incidence finnish cancer registry end 2011 standardised incidence ratios sirs defined ratios observed expected numbers cases latter ones based incidence entire finnish female population results overall incidence non gynaecological cancers reference population sir 0 98 95 confidence interval 0 90 1 06 incidence cancers gall bladder sir 1 42 1 26 1 58 biliary tract 1 19 1 04 1 35 kidney 1 22 1 14 1 31 increased significantly fewer cases expected urinary bladder cancer sir 0 70 0 61 0 78 lung cancer 0 87 0 81 0 92 colon cancer 0 94 0 89 0 99 types skin cancers consequence decreased incidence gynaecological cancers sir 0 74 0 71 0 77 breast cancer 0 60 0 58 0 61 sir cancer overall 0 84 0 83 0 85 conclusion study demonstrated grand multiparous women similar overall risk non gynaecological cancers women despite significant differences specific forms cancer pubmed","probabilities":0.9799733,"Title":"Incidence of cancer among grand multiparous women in Finland with special focus on non-gynaecological cancers: A population-based cohort study","Abstract":"BACKGROUND: Many studies have previously revealed evidence of an association between grand multiparity (five or more deliveries) and gynaecological cancer. Oestrogen has an impact on cancer formation and the amount of circulating oestrogen is significantly higher during pregnancy. Also the lifestyle of grand multiparous women differs somewhat from the average population. Considering these factors it is plausible that also non-gynaecological cancers are associated with multiparity. The aim of our study was to determine cancer incidence among grand multiparous women, with special attention to non-gynaecological cancers. MATERIAL AND METHODS: All 102 541 women alive in 1974-2011 and having had at least five deliveries were identified in the Finnish Population Register and followed up for cancer incidence through the Finnish Cancer Registry to the end of 2011. Standardised incidence ratios (SIRs) were defined as ratios between observed and expected numbers of cases, the latter ones based on incidence in the entire Finnish female population. RESULTS: The overall incidence of non-gynaecological cancers was the same as in the reference population (SIR 0.98, 95% confidence interval 0.90-1.06). The incidence of cancers of the gall-bladder (SIR 1.42, 1.26-1.58), biliary tract (1.19, 1.04-1.35) and kidney (1.22, 1.14-1.31) was increased. There were significantly fewer cases than expected of urinary bladder cancer (SIR 0.70, 0.61-0.78), lung cancer (0.87, 0.81-0.92), colon cancer (0.94, 0.89-0.99) and all types of skin cancers. As a consequence of the decreased incidence of gynaecological cancers (SIR 0.74, 0.71-0.77) and breast cancer (0.60, 0.58-0.61), the SIR for cancer overall was 0.84 (0.83-0.85). CONCLUSION: The study demonstrated that grand multiparous women have a similar overall risk of non-gynaecological cancers as other women, despite significant differences in some specific forms of cancer.","Source":"PubMed","category":"HUMAN","training_data":"Incidence of cancer among grand multiparous women in Finland with special focus on non-gynaecological cancers: A population-based cohort study BACKGROUND: Many studies have previously revealed evidence of an association between grand multiparity (five or more deliveries) and gynaecological cancer. Oestrogen has an impact on cancer formation and the amount of circulating oestrogen is significantly higher during pregnancy. Also the lifestyle of grand multiparous women differs somewhat from the average population. Considering these factors it is plausible that also non-gynaecological cancers are associated with multiparity. The aim of our study was to determine cancer incidence among grand multiparous women, with special attention to non-gynaecological cancers. MATERIAL AND METHODS: All 102 541 women alive in 1974-2011 and having had at least five deliveries were identified in the Finnish Population Register and followed up for cancer incidence through the Finnish Cancer Registry to the end of 2011. Standardised incidence ratios (SIRs) were defined as ratios between observed and expected numbers of cases, the latter ones based on incidence in the entire Finnish female population. RESULTS: The overall incidence of non-gynaecological cancers was the same as in the reference population (SIR 0.98, 95% confidence interval 0.90-1.06). The incidence of cancers of the gall-bladder (SIR 1.42, 1.26-1.58), biliary tract (1.19, 1.04-1.35) and kidney (1.22, 1.14-1.31) was increased. There were significantly fewer cases than expected of urinary bladder cancer (SIR 0.70, 0.61-0.78), lung cancer (0.87, 0.81-0.92), colon cancer (0.94, 0.89-0.99) and all types of skin cancers. As a consequence of the decreased incidence of gynaecological cancers (SIR 0.74, 0.71-0.77) and breast cancer (0.60, 0.58-0.61), the SIR for cancer overall was 0.84 (0.83-0.85). CONCLUSION: The study demonstrated that grand multiparous women have a similar overall risk of non-gynaecological cancers as other women, despite significant differences in some specific forms of cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"italian cancer figures report 2015 burden rare cancers italy objectives collaborative study based data collected network italian cancer registries airtum describes burden rare cancers italy estimated number new rare cancer cases yearly diagnosed incidence proportion patients alive diagnosis survival estimated number people still alive new cancer diagnosis prevalence provided 200 different cancer entities materials methods data herein presented provided airtum population based cancer registries crs covering nowadays 52 italian population monograph uses airtum database january 2015 includes malignant cancer cases diagnosed 1976 2010 cases coded according international classification diseases oncology icd o 3 data underwent standard quality checks described airtum data management protocol checked rare cancer specific quality indicators proposed published rarecare haemacare www rarecarenet eu www haemacare eu definition list rare cancers proposed rarecarenet information network rare cancers project adopted rare cancers entities defined combination topographical morphological codes icd o 3 incidence rate less 6 per 100 000 per year european population monograph presents 198 rare cancers grouped 14 major groups crude incidence rates estimated number new cancers occurring 2000 2010 divided overall population risk males females also gender specific tumours proportion rare cancers total cancers rare common site also calculated incidence rates sex age reported expected number new cases 2015 italy estimated assuming incidence italy airtum area one 5 year relative survival estimates cases aged 0 99 years diagnosed 2000 2008 airtum database followed 31 december 2009 calculated using complete cohort survival analysis estimate observed prevalence italy incidence follow data 11 crs period 1992 2006 used prevalence index date 1 january 2007 observed prevalence general population disentangled time prior reference date 2 years 2 5 years 15 years calculate complete prevalence proportion 1 january 2007 italy 15 year observed prevalence corrected completeness index order account cancer survivors diagnosed cancer registry activity started completeness index cancer age obtained means statistical regression models using incidence survival data available european rarecarenet data results total 339 403 tumours included incidence analysis annual incidence rate ir 198 rare cancers period 2000 2010 147 per 100 000 per year corresponding 89 000 new diagnoses italy year accounting 25 cancer five cancers rare european level rare italy ir higher 6 per 100 000 tumours diffuse large b cell lymphoma squamous cell carcinoma larynx whose irs italy 7 per 100 000 multiple myeloma ir 8 per 100 000 hepatocellular carcinoma ir 9 per 100 000 carcinoma thyroid gland ir 14 per 100 000 among remaining 193 rare cancers two thirds 139 annual ir 0 5 per 100 000 accounting 7 100 new cancers cases 25 cancer types ir ranged 0 5 1 per 100 000 accounting 10 000 new diagnoses 29 cancer types ir 1 6 per 100 000 accounting 41 000 new cancer cases among rare cancers diagnosed italy 7 rare haematological diseases ir 41 per 100 000 18 solid rare cancers among latter rare epithelial tumours digestive system common 23 ir 26 per 100 000 followed epithelial tumours head neck 17 ir 19 rare cancers female genital system 17 ir 17 endocrine tumours 13 including thyroid carcinomas less 1 ir 0 4 excluding thyroid carcinomas sarcomas 8 ir 9 per 100 000 central nervous system tumours rare epithelial tumours thoracic cavity 5 ir equal 6 5 per 100 000 respectively remaining rare male genital tumours ir 4 per 100 000 tumours eye ir 0 7 per 100 000 neuroendocrine tumours ir 4 per 100 000 embryonal tumours ir 0 4 per 100 000 rare skin tumours malignant melanoma mucosae ir 0 8 per 100 000 constituted 4 solid rare cancers patients rare cancers average younger common cancers essentially childhood cancers rare age 40 years common cancers breast prostate colon rectum lung became increasingly frequent 254 821 rare cancers diagnosed 2000 2008 5 year rs average 55 lower corresponding figures patients common cancers 68 rs lower rare cancers common cancers 1 year continued diverge 3 years gap remained constant 3 5 years diagnosis rare common cancers survival decreased increasing age five year rs similar high rare common cancers 54 years decreased age especially 54 years elderly 75 years 37 20 lower survival aged 55 64 years rare common cancers respectively estimated 900 000 people alive italy previous diagnosis rare cancer 2010 prevalence highest prevalence observed rare haematological diseases 278 per 100 000 rare tumours female genital system 265 per 100 000 low prevalence 10 prt 100 000 observed rare epithelial skin cancers rare epithelial tumours digestive system rare epithelial tumours thoracic cavity comments one four cancers cases diagnosed italy rare cancer agreement estimates 24 calculated europe overall italy group rare cancers combined include 5 cancer types ir 6 per 100 000 italy particular thyroid cancer ir 14 per 100 000 exclusion thyroid carcinoma rare cancers reduces proportion italy 2010 22 differences incidence across population due different distribution risk factors whether environmental lifestyle occupational genetic heterogeneous diagnostic intensity activity well different diagnostic capacity moreover heterogeneity accuracy registration may determine minor differences account rare cancers rare cancers worse prognosis common cancers 1 3 5 years diagnosis differences rare common cancers small 1 year diagnosis survival rare cancers declined markedly thereafter consistent idea treatments rare cancers less effective common cancers however differences stage diagnosis excluded 1 3 year rs rare cancers lower corresponding figures common cancers moreover rare cancers include many cancer entities bad prognosis 5 year rs 50 cancer head neck oesophagus small intestine ovary brain biliary tract liver pleura multiple myeloma acute myeloid lymphatic leukaemia contrast common cancer cases breast prostate colorectal cancers good prognosis high prevalence observed rare haematological diseases rare tumours female genital system due high incidence majority haematological diseases rare gynaecological cancers added fairly high incidence rates relatively good prognosis low prevalence rare epithelial tumours digestive system due low survival rates majority tumours included group oesophagus stomach small intestine pancreas liver regardless high incidence rate rare epithelial cancers sites airtum study confirms rare cancers major public health problem italy provides quantitative estimations first time italy problem long known exist monograph provides detailed epidemiologic indicators almost 200 rare cancers majority 72 rare ir 0 5 per 100 000 data major interest different stakeholders health care planners find useful information herein properly plan think reorganise health care services researchers numbers design clinical trials considering alternative study designs statistical approaches population based cancer registries good quality data best source information describe rare cancer burden population pubmed","probabilities":0.962963,"Title":"Italian cancer figures--Report 2015: The burden of rare cancers in Italy","Abstract":"OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet \"Information Network on Rare Cancers\" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population.","Source":"PubMed","category":"HUMAN","training_data":"Italian cancer figures--Report 2015: The burden of rare cancers in Italy OBJECTIVES: This collaborative study, based on data collected by the network of Italian Cancer Registries (AIRTUM), describes the burden of rare cancers in Italy. Estimated number of new rare cancer cases yearly diagnosed (incidence), proportion of patients alive after diagnosis (survival), and estimated number of people still alive after a new cancer diagnosis (prevalence) are provided for about 200 different cancer entities. MATERIALS AND METHODS: Data herein presented were provided by AIRTUM population- based cancer registries (CRs), covering nowadays 52% of the Italian population. This monograph uses the AIRTUM database (January 2015), which includes all malignant cancer cases diagnosed between 1976 and 2010. All cases are coded according to the International Classification of Diseases for Oncology (ICD-O-3). Data underwent standard quality checks (described in the AIRTUM data management protocol) and were checked against rare-cancer specific quality indicators proposed and published by RARECARE and HAEMACARE (www.rarecarenet.eu; www.haemacare.eu). The definition and list of rare cancers proposed by the RARECAREnet \"Information Network on Rare Cancers\" project were adopted: rare cancers are entities (defined as a combination of topographical and morphological codes of the ICD-O-3) having an incidence rate of less than 6 per 100,000 per year in the European population. This monograph presents 198 rare cancers grouped in 14 major groups. Crude incidence rates were estimated as the number of all new cancers occurring in 2000-2010 divided by the overall population at risk, for males and females (also for gender-specific tumours).The proportion of rare cancers out of the total cancers (rare and common) by site was also calculated. Incidence rates by sex and age are reported. The expected number of new cases in 2015 in Italy was estimated assuming the incidence in Italy to be the same as in the AIRTUM area. One- and 5-year relative survival estimates of cases aged 0-99 years diagnosed between 2000 and 2008 in the AIRTUM database, and followed up to 31 December 2009, were calculated using complete cohort survival analysis. To estimate the observed prevalence in Italy, incidence and follow-up data from 11 CRs for the period 1992-2006 were used, with a prevalence index date of 1 January 2007. Observed prevalence in the general population was disentangled by time prior to the reference date (≤2 years, 2-5 years, ≤15 years). To calculate the complete prevalence proportion at 1 January 2007 in Italy, the 15-year observed prevalence was corrected by the completeness index, in order to account for those cancer survivors diagnosed before the cancer registry activity started. The completeness index by cancer and age was obtained by means of statistical regression models, using incidence and survival data available in the European RARECAREnet data. RESULTS: In total, 339,403 tumours were included in the incidence analysis. The annual incidence rate (IR) of all 198 rare cancers in the period 2000-2010 was 147 per 100,000 per year, corresponding to about 89,000 new diagnoses in Italy each year, accounting for 25% of all cancer. Five cancers, rare at European level, were not rare in Italy because their IR was higher than 6 per 100,000; these tumours were: diffuse large B-cell lymphoma and squamous cell carcinoma of larynx (whose IRs in Italy were 7 per 100,000), multiple myeloma (IR: 8 per 100,000), hepatocellular carcinoma (IR: 9 per 100,000) and carcinoma of thyroid gland (IR: 14 per 100,000). Among the remaining 193 rare cancers, more than two thirds (No. 139) had an annual IR <0.5 per 100,000, accounting for about 7,100 new cancers cases; for 25 cancer types, the IR ranged between 0.5 and 1 per 100,000, accounting for about 10,000 new diagnoses; while for 29 cancer types the IR was between 1 and 6 per 100,000, accounting for about 41,000 new cancer cases. Among all rare cancers diagnosed in Italy, 7% were rare haematological diseases (IR: 41 per 100,000), 18% were solid rare cancers. Among the latter, the rare epithelial tumours of the digestive system were the most common (23%, IR: 26 per 100,000), followed by epithelial tumours of head and neck (17%, IR: 19) and rare cancers of the female genital system (17%, IR: 17), endocrine tumours (13% including thyroid carcinomas and less than 1% with an IR of 0.4 excluding thyroid carcinomas), sarcomas (8%, IR: 9 per 100,000), central nervous system tumours and rare epithelial tumours of the thoracic cavity (5%with an IR equal to 6 and 5 per 100,000, respectively). The remaining (rare male genital tumours, IR: 4 per 100,000; tumours of eye, IR: 0.7 per 100,000; neuroendocrine tumours, IR: 4 per 100,000; embryonal tumours, IR: 0.4 per 100,000; rare skin tumours and malignant melanoma of mucosae, IR: 0.8 per 100,000) each constituted <4% of all solid rare cancers. Patients with rare cancers were on average younger than those with common cancers. Essentially, all childhood cancers were rare, while after age 40 years, the common cancers (breast, prostate, colon, rectum, and lung) became increasingly more frequent. For 254,821 rare cancers diagnosed in 2000-2008, 5-year RS was on average 55%, lower than the corresponding figures for patients with common cancers (68%). RS was lower for rare cancers than for common cancers at 1 year and continued to diverge up to 3 years, while the gap remained constant from 3 to 5 years after diagnosis. For rare and common cancers, survival decreased with increasing age. Five-year RS was similar and high for both rare and common cancers up to 54 years; it decreased with age, especially after 54 years, with the elderly (75+ years) having a 37% and 20% lower survival than those aged 55-64 years for rare and common cancers, respectively. We estimated that about 900,000 people were alive in Italy with a previous diagnosis of a rare cancer in 2010 (prevalence). The highest prevalence was observed for rare haematological diseases (278 per 100,000) and rare tumours of the female genital system (265 per 100,000). Very low prevalence (<10 prt 100,000) was observed for rare epithelial skin cancers, for rare epithelial tumours of the digestive system and rare epithelial tumours of the thoracic cavity. COMMENTS: One in four cancers cases diagnosed in Italy is a rare cancer, in agreement with estimates of 24% calculated in Europe overall. In Italy, the group of all rare cancers combined, include 5 cancer types with an IR>6 per 100,000 in Italy, in particular thyroid cancer (IR: 14 per 100,000).The exclusion of thyroid carcinoma from rare cancers reduces the proportion of them in Italy in 2010 to 22%. Differences in incidence across population can be due to the different distribution of risk factors (whether environmental, lifestyle, occupational, or genetic), heterogeneous diagnostic intensity activity, as well as different diagnostic capacity; moreover heterogeneity in accuracy of registration may determine some minor differences in the account of rare cancers. Rare cancers had worse prognosis than common cancers at 1, 3, and 5 years from diagnosis. Differences between rare and common cancers were small 1 year after diagnosis, but survival for rare cancers declined more markedly thereafter, consistent with the idea that treatments for rare cancers are less effective than those for common cancers. However, differences in stage at diagnosis could not be excluded, as 1- and 3-year RS for rare cancers was lower than the corresponding figures for common cancers. Moreover, rare cancers include many cancer entities with a bad prognosis (5-year RS <50%): cancer of head and neck, oesophagus, small intestine, ovary, brain, biliary tract, liver, pleura, multiple myeloma, acute myeloid and lymphatic leukaemia; in contrast, most common cancer cases are breast, prostate, and colorectal cancers, which have a good prognosis. The high prevalence observed for rare haematological diseases and rare tumours of the female genital system is due to their high incidence (the majority of haematological diseases are rare and gynaecological cancers added up to fairly high incidence rates) and relatively good prognosis. The low prevalence of rare epithelial tumours of the digestive system was due to the low survival rates of the majority of tumours included in this group (oesophagus, stomach, small intestine, pancreas, and liver), regardless of the high incidence rate of rare epithelial cancers of these sites. This AIRTUM study confirms that rare cancers are a major public health problem in Italy and provides quantitative estimations, for the first time in Italy, to a problem long known to exist. This monograph provides detailed epidemiologic indicators for almost 200 rare cancers, the majority of which (72%) are very rare (IR<0.5 per 100,000). These data are of major interest for different stakeholders. Health care planners can find useful information herein to properly plan and think of how to reorganise health care services. Researchers now have numbers to design clinical trials considering alternative study designs and statistical approaches. Population-based cancer registries with good quality data are the best source of information to describe the rare cancer burden in a population. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact type preoperative biliary drainage patients distal cholangiocarcinoma background surgical results patients resected distal cholangiocarcinoma dcc evaluated elucidate prognostic impact type preoperative biliary drainage pbd methods eighty eight patients resected dcc stratified two groups according type pbd percutaneous transhepatic biliary drainage ptbd group n 25 endoscopic biliary drainage ebd group n 63 results overall 5 year survival rate patients ptbd group poorer ebd group 24 vs 52 p 0 020 univariate analysis ptbd pancreatic invasion perineural invasion lymph node involvement significant prognostic factors poor overall survival multivariate analysis ptbd significantly independent prognostic factor poor overall survival incidence liver metastasis significantly higher ptbd group ebd group 32 0 vs 13 3 p 0 034 conclusions ptbd avoided much possible patients dcc since patients underwent ptbd poorer overall survival higher incidence liver metastasis underwent ebd pubmed","probabilities":0.9799733,"Title":"Prognostic impact of type of preoperative biliary drainage in patients with distal cholangiocarcinoma","Abstract":"BACKGROUND: Surgical results of patients with resected distal cholangiocarcinoma (DCC) were evaluated to elucidate prognostic impact of the type of preoperative biliary drainage (PBD). METHODS: Eighty-eight patients with resected DCC were stratified into two groups according to the type of PBD: the percutaneous transhepatic biliary drainage (PTBD) group (n = 25) and the endoscopic biliary drainage (EBD) group (n = 63). RESULTS: Overall 5-year survival rate of the patients in the PTBD group was poorer than in the EBD group (24% vs. 52%, P = 0.020). On univariate analysis, PTBD, pancreatic invasion, perineural invasion, and lymph node involvement were significant prognostic factors for poor overall survival. On multivariate analysis, PTBD was the only significantly independent prognostic factor for poor overall survival. The incidence of liver metastasis was significantly higher in the PTBD group than in the EBD group (32.0% vs. 13.3%, P = 0.034). CONCLUSIONS: PTBD should be avoided as much as possible in patients with DCC since the patients who underwent PTBD had poorer overall survival and higher incidence of liver metastasis than those who underwent EBD.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic impact of type of preoperative biliary drainage in patients with distal cholangiocarcinoma BACKGROUND: Surgical results of patients with resected distal cholangiocarcinoma (DCC) were evaluated to elucidate prognostic impact of the type of preoperative biliary drainage (PBD). METHODS: Eighty-eight patients with resected DCC were stratified into two groups according to the type of PBD: the percutaneous transhepatic biliary drainage (PTBD) group (n = 25) and the endoscopic biliary drainage (EBD) group (n = 63). RESULTS: Overall 5-year survival rate of the patients in the PTBD group was poorer than in the EBD group (24% vs. 52%, P = 0.020). On univariate analysis, PTBD, pancreatic invasion, perineural invasion, and lymph node involvement were significant prognostic factors for poor overall survival. On multivariate analysis, PTBD was the only significantly independent prognostic factor for poor overall survival. The incidence of liver metastasis was significantly higher in the PTBD group than in the EBD group (32.0% vs. 13.3%, P = 0.034). CONCLUSIONS: PTBD should be avoided as much as possible in patients with DCC since the patients who underwent PTBD had poorer overall survival and higher incidence of liver metastasis than those who underwent EBD. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival benefit hepatopancreatoduodenectomy cholangiocarcinoma comparison hepatectomy pancreatoduodenectomy background perihilar distal cholangiocarcinoma remain difficult treat long term survival poor conducted retrospective study patients cholangiocarcinoma examine whether hepatopancreatoduodenectomy comparison standard surgeries provides survival benefit methods subjects 75 patients perihilar distal cholangiocarcinoma april 1997 may 2007 underwent hepatectomy bile duct resection hx n 29 pancreatoduodenectomy pd n 32 hepatopancreatoduodenectomy hpd n 14 hospital compared surgical outcomes survival groups identified factors negatively influencing survival results morbidity hospital mortality differ significantly groups hx group 34 10 respectively pd group 44 3 hpd 57 0 overall median survival time 39 months overall 5 year survival including hospital mortality 42 respective group values follows hx 24 months 31 pd 51 months 49 hpd 63 months 50 although number patients small survival hpd influenced type invasion whether widespread intramural invasion n 8 superficial spread n 4 hepatoduodenal ligament invasion n 2 multivariate analysis cox proportional hazards model showed perineural invasion p 007 decreased curability r1 2 resection p 017 independent risk factors influencing survival conclusions cases perihilar distal cholangiocarcinoma aggressive surgery must aimed overcoming perineural invasion findings indicate hpd improves survival patients undergoing surgery widespread cholangiocarcinoma comparison standard surgeries pubmed","probabilities":0.9799733,"Title":"Survival benefit of hepatopancreatoduodenectomy for cholangiocarcinoma in comparison to hepatectomy or pancreatoduodenectomy","Abstract":"BACKGROUND: Perihilar and distal cholangiocarcinoma remain difficult to treat, and long-term survival is poor. We conducted a retrospective study of patients with cholangiocarcinoma to examine whether hepatopancreatoduodenectomy, in comparison to standard surgeries, provides a survival benefit. METHODS: Subjects were 75 patients with perihilar or distal cholangiocarcinoma who, between April 1997 and May 2007, underwent hepatectomy with bile duct resection (Hx, n = 29), pancreatoduodenectomy (PD, n = 32), or hepatopancreatoduodenectomy (HPD, n = 14) at our hospital. We compared surgical outcomes and survival between groups and identified factors negatively influencing survival. RESULTS: Morbidity and in-hospital mortality did not differ significantly between groups (Hx group, 34% and 10%, respectively; PD group, 44% and 3%; and HPD, 57% and 0%). The overall median survival time was 39 months, and overall 5-year survival (including in-hospital mortality) was 42%. Respective group values were as follows: Hx, 24 months and 31%; PD, 51 months and 49%, and HPD, 63 months and 50%. Although the number of patients was small, survival in the HPD was not influenced by the type of invasion whether widespread intramural invasion (n = 8), superficial spread (n = 4), or hepatoduodenal ligament invasion (n = 2). Multivariate analysis (Cox proportional hazards model) showed only perineural invasion (p = .007) and decreased curability (R1/2 resection) (p = .017) to be independent risk factors influencing survival. CONCLUSIONS: In cases of perihilar or distal cholangiocarcinoma, aggressive surgery must be aimed at overcoming perineural invasion. Our findings indicate that HPD improves survival of patients undergoing surgery for widespread cholangiocarcinoma in comparison to standard surgeries.","Source":"PubMed","category":"HUMAN","training_data":"Survival benefit of hepatopancreatoduodenectomy for cholangiocarcinoma in comparison to hepatectomy or pancreatoduodenectomy BACKGROUND: Perihilar and distal cholangiocarcinoma remain difficult to treat, and long-term survival is poor. We conducted a retrospective study of patients with cholangiocarcinoma to examine whether hepatopancreatoduodenectomy, in comparison to standard surgeries, provides a survival benefit. METHODS: Subjects were 75 patients with perihilar or distal cholangiocarcinoma who, between April 1997 and May 2007, underwent hepatectomy with bile duct resection (Hx, n = 29), pancreatoduodenectomy (PD, n = 32), or hepatopancreatoduodenectomy (HPD, n = 14) at our hospital. We compared surgical outcomes and survival between groups and identified factors negatively influencing survival. RESULTS: Morbidity and in-hospital mortality did not differ significantly between groups (Hx group, 34% and 10%, respectively; PD group, 44% and 3%; and HPD, 57% and 0%). The overall median survival time was 39 months, and overall 5-year survival (including in-hospital mortality) was 42%. Respective group values were as follows: Hx, 24 months and 31%; PD, 51 months and 49%, and HPD, 63 months and 50%. Although the number of patients was small, survival in the HPD was not influenced by the type of invasion whether widespread intramural invasion (n = 8), superficial spread (n = 4), or hepatoduodenal ligament invasion (n = 2). Multivariate analysis (Cox proportional hazards model) showed only perineural invasion (p = .007) and decreased curability (R1/2 resection) (p = .017) to be independent risk factors influencing survival. CONCLUSIONS: In cases of perihilar or distal cholangiocarcinoma, aggressive surgery must be aimed at overcoming perineural invasion. Our findings indicate that HPD improves survival of patients undergoing surgery for widespread cholangiocarcinoma in comparison to standard surgeries. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tobacco smoking risk gallbladder disease tobacco smoking inconsistently associated gallbladder disease risk clarify association conducted systematic review meta analysis cohort studies published subject searched pubmed embase databases studies smoking gallbladder disease january 9th 2015 prospective studies included reported relative risk estimates 95 confidence intervals gallbladder disease associated current former ever smoking number cigarettes per day summary relative risks estimated use random effects model identified ten prospective studies including 59 530 gallbladder disease cases among 4 213 482 participants included meta analysis summary rr 1 19 95 ci 1 12 1 28 2 46 9 n 6 current smokers 1 10 95 ci 1 07 1 13 2 0 n 6 former smokers 1 15 95 ci 1 13 1 18 2 0 n 7 ever smokers dose response analysis summary relative risk 1 11 95 ci 1 08 1 14 2 33 n 3 per 10 cigarettes per day although indication nonlinearity dose dependent positive association increasing number cigarettes smoked per day current meta analysis provides evidence increased risk gallbladder disease associated tobacco smoking pubmed","probabilities":0.9799733,"Title":"Tobacco smoking and the risk of gallbladder disease","Abstract":"Tobacco smoking has been inconsistently associated with gallbladder disease risk. To clarify the association we conducted a systematic review and meta-analysis of cohort studies published on the subject. We searched the PubMed and Embase databases for studies of smoking and gallbladder disease up to January 9th 2015. Prospective studies were included if they reported relative risk estimates and 95 % confidence intervals of gallbladder disease associated with current, former or ever smoking and by number of cigarettes per day. Summary relative risks were estimated by use of a random effects model. We identified ten prospective studies including 59,530 gallbladder disease cases among 4,213,482 participants that could be included in the meta-analysis. The summary RR was 1.19 (95 % CI 1.12-1.28, I(2) = 46.9 %, n = 6) for current smokers, 1.10 (95 % CI 1.07-1.13, I(2) = 0 %, n = 6) for former smokers and 1.15 (95 % CI 1.13-1.18, I(2) = 0 %, n = 7) for ever smokers. In the dose-response analysis the summary relative risk was 1.11 (95 % CI 1.08-1.14, I(2) = 33 %, n = 3) per 10 cigarettes per day and although there was indication of nonlinearity there was a dose-dependent positive association with increasing number of cigarettes smoked per day. The current meta-analysis provides evidence of an increased risk of gallbladder disease associated with tobacco smoking.","Source":"PubMed","category":"HUMAN","training_data":"Tobacco smoking and the risk of gallbladder disease Tobacco smoking has been inconsistently associated with gallbladder disease risk. To clarify the association we conducted a systematic review and meta-analysis of cohort studies published on the subject. We searched the PubMed and Embase databases for studies of smoking and gallbladder disease up to January 9th 2015. Prospective studies were included if they reported relative risk estimates and 95 % confidence intervals of gallbladder disease associated with current, former or ever smoking and by number of cigarettes per day. Summary relative risks were estimated by use of a random effects model. We identified ten prospective studies including 59,530 gallbladder disease cases among 4,213,482 participants that could be included in the meta-analysis. The summary RR was 1.19 (95 % CI 1.12-1.28, I(2) = 46.9 %, n = 6) for current smokers, 1.10 (95 % CI 1.07-1.13, I(2) = 0 %, n = 6) for former smokers and 1.15 (95 % CI 1.13-1.18, I(2) = 0 %, n = 7) for ever smokers. In the dose-response analysis the summary relative risk was 1.11 (95 % CI 1.08-1.14, I(2) = 33 %, n = 3) per 10 cigarettes per day and although there was indication of nonlinearity there was a dose-dependent positive association with increasing number of cigarettes smoked per day. The current meta-analysis provides evidence of an increased risk of gallbladder disease associated with tobacco smoking. PubMed","prediction_labels":"HUMAN"},{"cleaned":"predictive model neoplastic potential gallbladder polyp goal provide statistical predictive model neoplastic potential gallbladder polyp gbp background many studies attempted define risk factors neoplastic potential gbp remains difficult precisely adapt reported risk factors decision surgery estimating probability neoplastic potential gbp using combination several risk factors surgical resection useful patient consultation study collected data patients confirmed gbp cholecystectomy samsung medical center january 1997 march 2015 definite evidence malignancy adjacent organ invasion metastasis preoperative imaging studies polyp 15 mm absence proper preoperative ultrasonographic imaging excluded total 1976 patients enrolled make validate predictive model divided cohort modeling group n 979 validation group n 997 clinical information ultrasonographic findings blood tests retrospectively analyzed results clinical factors older age single lesion sessile shape polyp size showed statistical significance neoplastic potential gbp modeling group predictive model neoplastic potential gbp constructed utilizing statistical outcome modeling group statistical validation performed validation group determine optimal clinical sensitivity specificity predictive model optimal cut value neoplastic probability 7 4 conclusions predictive model neoplastic potential gbp may support clinical decisions cholecystectomy stn","probabilities":0.9799733,"Title":"Predictive Model For Neoplastic Potential Of Gallbladder Polyp","Abstract":"Goal: To provide the statistical predictive model for neoplastic potential of gallbladder polyp (GBP). \r\n\r\n Background: Many studies have attempted to define the risk factors for neoplastic potential of GBP. It remains difficult to precisely adapt the reported risk factors for the decision of surgery. Estimating the probability for neoplastic potential of GBP using a combination of several risk factors before surgical resection would be useful in patient consultation. \r\n\r\n Study: We collected data of patients confirmed as GBP through cholecystectomy at Samsung Medical Center between January 1997 and March 2015. Those with a definite evidence for malignancy, such as adjacent organ invasion, metastasis on preoperative imaging studies, polyp >15 mm, and absence of proper preoperative ultrasonographic imaging were excluded. A total of 1976 patients were enrolled. To make and validate the predictive model, we divided the cohort into the modeling group (n=979) and validation group (n=997). Clinical information, ultrasonographic findings, and blood tests were retrospectively analyzed. \r\n\r\n Results: Clinical factors of older age, single lesion, sessile shape, and polyp size showed statistical significance for neoplastic potential of GBP in the modeling group. A predictive model for neoplastic potential of GBP was constructed utilizing the statistical outcome of the modeling group. Statistical validation was performed with the validation group to determine the optimal clinical sensitivity and specificity of the predictive model. Optimal cut-off value for neoplastic probability was 7.4%. \r\n\r\n Conclusions: The predictive model for neoplastic potential of GBP may support clinical decisions before cholecystectomy.","Source":"STN","category":"HUMAN","training_data":"Predictive Model For Neoplastic Potential Of Gallbladder Polyp Goal: To provide the statistical predictive model for neoplastic potential of gallbladder polyp (GBP). \r\n\r\n Background: Many studies have attempted to define the risk factors for neoplastic potential of GBP. It remains difficult to precisely adapt the reported risk factors for the decision of surgery. Estimating the probability for neoplastic potential of GBP using a combination of several risk factors before surgical resection would be useful in patient consultation. \r\n\r\n Study: We collected data of patients confirmed as GBP through cholecystectomy at Samsung Medical Center between January 1997 and March 2015. Those with a definite evidence for malignancy, such as adjacent organ invasion, metastasis on preoperative imaging studies, polyp >15 mm, and absence of proper preoperative ultrasonographic imaging were excluded. A total of 1976 patients were enrolled. To make and validate the predictive model, we divided the cohort into the modeling group (n=979) and validation group (n=997). Clinical information, ultrasonographic findings, and blood tests were retrospectively analyzed. \r\n\r\n Results: Clinical factors of older age, single lesion, sessile shape, and polyp size showed statistical significance for neoplastic potential of GBP in the modeling group. A predictive model for neoplastic potential of GBP was constructed utilizing the statistical outcome of the modeling group. Statistical validation was performed with the validation group to determine the optimal clinical sensitivity and specificity of the predictive model. Optimal cut-off value for neoplastic probability was 7.4%. \r\n\r\n Conclusions: The predictive model for neoplastic potential of GBP may support clinical decisions before cholecystectomy. STN","prediction_labels":"HUMAN"},{"cleaned":"liver fluke granulin promotes extracellular vesicle mediated crosstalk cellular microenvironment conducive cholangiocarcinoma crosstalk malignant neighboring cells contributes tumor growth east asia infection liver fluke major risk factor cholangiocarcinoma cca liver fluke opisthorchis viverrini secretes growth factor termed liver fluke granulin homologue human progranulin contributes significantly biliary tract fibrosis morbidity extracellular vesicle ev mediated transfer mrnas human cholangiocytes na ve recipient cells investigated following exposure liver fluke granulin minimize influence endogenous progranulin cognate gene inactivated using crispr cas9 based gene knock several progranulin depleted cell lines termed hupgrn h69 established lines exhibited 80 reductions levels specific transcript progranulin gene edited cells within evs released cells profiles extracellular vesicle rnas evrna hupgrn h69 cca associated characteristics revealed paucity transcripts estrogen wnt signaling pathways peptidase inhibitors tyrosine phosphatase related cellular processes including oncogenic transformation several cca specific evrnas including mapk akt pathway members induced exposure liver fluke granulin comparison estrogen wnt pi3k tgf signaling cca pathway mrnas upregulated wild type h69 cells exposed liver fluke granulin cca associated evrnas modified cca microenvironment na ve cells co cultured evs hupgrn h69 cells exposed liver fluke granulin induced translation mapk phosphorylation related protein na ve recipient cells comparison control recipient cells exosome mediated crosstalk response liver fluke granulin promoted cca specific program mapk pathway turn established cca conducive disposition stn","probabilities":0.9467213,"Title":"Liver Fluke Granulin Promotes Extracellular Vesicle-Mediated Crosstalk And Cellular Microenvironment Conducive To Cholangiocarcinoma","Abstract":"Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the liver fluke is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor termed liver fluke granulin, a homologue of the human progranulin, which contributes significantly to biliary tract fibrosis and morbidity. Here, extracellular vesicle (EV)-mediated transfer of mRNAs from human cholangiocytes to naïve recipient cells was investigated following exposure to liver fluke granulin. To minimize the influence of endogenous progranulin, its cognate gene was inactivated using CRISPR/Cas9-based gene knock-out. Several progranulin-depleted cell lines, termed ΔhuPGRN-H69, were established. These lines exhibited >80% reductions in levels of specific transcript and progranulin, both in gene-edited cells and within EVs released by these cells. Profiles of extracellular vesicle RNAs (evRNA) from ΔhuPGRN-H69 for CCA-associated characteristics revealed a paucity of transcripts for estrogen- and Wnt-signaling pathways, peptidase inhibitors and tyrosine phosphatase related to cellular processes including oncogenic transformation. Several CCA-specific evRNAs including MAPK/AKT pathway members were induced by exposure to liver fluke granulin. By comparison, estrogen, Wnt/PI3K and TGF signaling and other CCA pathway mRNAs were upregulated in wild type H69 cells exposed to liver fluke granulin. Of these, CCA-associated evRNAs modified the CCA microenvironment in naïve cells co-cultured with EVs from ΔhuPGRN-H69 cells exposed to liver fluke granulin, and induced translation of MAPK phosphorylation related-protein in naïve recipient cells in comparison with control recipient cells. Exosome-mediated crosstalk in response to liver fluke granulin promoted a CCA-specific program through MAPK pathway which, in turn, established a CCA-conducive disposition.","Source":"STN","category":"ANIMAL","training_data":"Liver Fluke Granulin Promotes Extracellular Vesicle-Mediated Crosstalk And Cellular Microenvironment Conducive To Cholangiocarcinoma Crosstalk between malignant and neighboring cells contributes to tumor growth. In East Asia, infection with the liver fluke is a major risk factor for cholangiocarcinoma (CCA). The liver fluke Opisthorchis viverrini secretes a growth factor termed liver fluke granulin, a homologue of the human progranulin, which contributes significantly to biliary tract fibrosis and morbidity. Here, extracellular vesicle (EV)-mediated transfer of mRNAs from human cholangiocytes to naïve recipient cells was investigated following exposure to liver fluke granulin. To minimize the influence of endogenous progranulin, its cognate gene was inactivated using CRISPR/Cas9-based gene knock-out. Several progranulin-depleted cell lines, termed ΔhuPGRN-H69, were established. These lines exhibited >80% reductions in levels of specific transcript and progranulin, both in gene-edited cells and within EVs released by these cells. Profiles of extracellular vesicle RNAs (evRNA) from ΔhuPGRN-H69 for CCA-associated characteristics revealed a paucity of transcripts for estrogen- and Wnt-signaling pathways, peptidase inhibitors and tyrosine phosphatase related to cellular processes including oncogenic transformation. Several CCA-specific evRNAs including MAPK/AKT pathway members were induced by exposure to liver fluke granulin. By comparison, estrogen, Wnt/PI3K and TGF signaling and other CCA pathway mRNAs were upregulated in wild type H69 cells exposed to liver fluke granulin. Of these, CCA-associated evRNAs modified the CCA microenvironment in naïve cells co-cultured with EVs from ΔhuPGRN-H69 cells exposed to liver fluke granulin, and induced translation of MAPK phosphorylation related-protein in naïve recipient cells in comparison with control recipient cells. Exosome-mediated crosstalk in response to liver fluke granulin promoted a CCA-specific program through MAPK pathway which, in turn, established a CCA-conducive disposition. STN","prediction_labels":"ANIMAL"},{"cleaned":"advanced presentation gallbladder cancer epidemioclinicopathological study evaluate risk factors assess outcome objective evaluate risk factors assess short term prognosis independent prognostic factors cases gallbladder cancer methods retrospective analysis data 52 patients gallbladder cancer done clinical presentation laboratory investigations treatment given operative findings histopathological findings reviewed results forty four patients unresectable presentation 2 year survival rate early gallbladder cancer 100 29 2 advanced stage group conclusion overall 2 year survival rate 39 58 tnm stage important factor affecting survival stn","probabilities":0.9799733,"Title":"Advanced Presentation Of Gallbladder Cancer: Epidemioclinicopathological Study To Evaluate The Risk Factors And Assess The Outcome","Abstract":"Objective: To evaluate the risk factors and assess the short-term prognosis and independent prognostic factors of cases of gallbladder cancer. \r\n\r\n Methods: A retrospective analysis of the data of 52 patients of gallbladder cancer was done. Clinical presentation, laboratory investigations, treatment given, operative findings and histopathological findings were reviewed. \r\n\r\n Results: Forty-four patients were unresectable at presentation. A 2-year survival rate for early gallbladder cancer was 100% while it was only 29.2% in the advanced stage group. \r\n\r\n Conclusion: The overall 2-year survival rate was 39.58%. The TNM stage was the most important factor affecting the survival.","Source":"STN","category":"HUMAN","training_data":"Advanced Presentation Of Gallbladder Cancer: Epidemioclinicopathological Study To Evaluate The Risk Factors And Assess The Outcome Objective: To evaluate the risk factors and assess the short-term prognosis and independent prognostic factors of cases of gallbladder cancer. \r\n\r\n Methods: A retrospective analysis of the data of 52 patients of gallbladder cancer was done. Clinical presentation, laboratory investigations, treatment given, operative findings and histopathological findings were reviewed. \r\n\r\n Results: Forty-four patients were unresectable at presentation. A 2-year survival rate for early gallbladder cancer was 100% while it was only 29.2% in the advanced stage group. \r\n\r\n Conclusion: The overall 2-year survival rate was 39.58%. The TNM stage was the most important factor affecting the survival. STN","prediction_labels":"HUMAN"},{"cleaned":"splenic fdg uptake predicts poor prognosis patients unresectable cholangiocarcinoma aim diffuse splenic 18f fluorodeoxyglucose fdg uptake shown associated concurrent inflammation evaluated prognostic value diffuse splenic fdg uptake predicting prognosis cholangiocarcinoma patients patients methods sixty four patients unresectable cholangiocarcinoma performed positron emission tomography computed tomography pet ct using fdg july 2009 april 2012 patients divided two groups according splenic fdg uptake relative hepatic fdg uptake eleven patients showing splenic fdg uptake exceeding hepatic uptake included group 53 patients hepatic fdg uptake exceeding splenic uptake included group b prognostic factors overall survival evaluated using log rank test variables probability less equal 0 1 univariate analysis considered possible independent factors cox proportional hazards model used analyze univariate multivariate analysis results mean standardized uptake value liver liver suvmean spleen suvmean l ratio 1 p 0 0034 wbc 10 000 p 0 1155 cea 30 p 0 0946 predictors overall survival univariate analysis subsequent multivariate analysis l ratio 1 remained significant independent predictor poor prognosis hr 6 0153 95 ci 1 7193 21 0460 p 0 0052 conclusion study shown splenic fdg uptake predictor overall survival unresectable cholangiocarcinoma patients stn","probabilities":0.9799733,"Title":"Splenic Fdg Uptake Predicts Poor Prognosis In Patients With Unresectable Cholangiocarcinoma","Abstract":"Aim: Diffuse splenic 18F-Fluorodeoxyglucose (FDG) uptake has shown to be associated with concurrent inflammation. We evaluated the prognostic value of diffuse splenic FDG uptake for predicting prognosis in cholangiocarcinoma patients. \r\n\r\n Patients, methods: Sixty-four patients with unresectable cholangiocarcinoma performed Positron emission tomography/computed tomography (PET/CT) using FDG between July 2009 and April 2012. Patients were divided into two groups according to splenic FDG uptake relative to hepatic FDG uptake. Eleven patients showing splenic FDG uptake exceeding hepatic uptake were included in group A, while 53 patients with hepatic FDG uptake exceeding splenic uptake were included in group B. Prognostic factors for overall survival were evaluated using log-rank test. Variables with a probability of less than or equal to 0.1 on univariate analysis were considered as possible independent factors. Cox-proportional hazards model was used to analyze univariate and multivariate analysis. \r\n\r\n Results: Mean standardized uptake value of the liver (Liver SUVmean)/Spleen SUVmean (L/S) ratio <1 (p = 0.0034), WBC > 10 000 (p = 0.1155) and CEA >30 (p = 0.0946) were predictors of overall survival on univariate analysis. In a subsequent multivariate analysis, L/S ratio <1 remained a significant independent predictor of poor prognosis (HR 6.0153, 95% CI, 1.7193-21.0460, p = 0.0052). \r\n\r\n Conclusion: Our study has shown that splenic FDG uptake could be a predictor of overall survival of unresectable cholangiocarcinoma patients.","Source":"STN","category":"HUMAN","training_data":"Splenic Fdg Uptake Predicts Poor Prognosis In Patients With Unresectable Cholangiocarcinoma Aim: Diffuse splenic 18F-Fluorodeoxyglucose (FDG) uptake has shown to be associated with concurrent inflammation. We evaluated the prognostic value of diffuse splenic FDG uptake for predicting prognosis in cholangiocarcinoma patients. \r\n\r\n Patients, methods: Sixty-four patients with unresectable cholangiocarcinoma performed Positron emission tomography/computed tomography (PET/CT) using FDG between July 2009 and April 2012. Patients were divided into two groups according to splenic FDG uptake relative to hepatic FDG uptake. Eleven patients showing splenic FDG uptake exceeding hepatic uptake were included in group A, while 53 patients with hepatic FDG uptake exceeding splenic uptake were included in group B. Prognostic factors for overall survival were evaluated using log-rank test. Variables with a probability of less than or equal to 0.1 on univariate analysis were considered as possible independent factors. Cox-proportional hazards model was used to analyze univariate and multivariate analysis. \r\n\r\n Results: Mean standardized uptake value of the liver (Liver SUVmean)/Spleen SUVmean (L/S) ratio <1 (p = 0.0034), WBC > 10 000 (p = 0.1155) and CEA >30 (p = 0.0946) were predictors of overall survival on univariate analysis. In a subsequent multivariate analysis, L/S ratio <1 remained a significant independent predictor of poor prognosis (HR 6.0153, 95% CI, 1.7193-21.0460, p = 0.0052). \r\n\r\n Conclusion: Our study has shown that splenic FDG uptake could be a predictor of overall survival of unresectable cholangiocarcinoma patients. STN","prediction_labels":"HUMAN"},{"cleaned":"adjuvant therapy patients gallbladder carcinoma aim study aimed investigate effects adjuvant therapy chemotherapeutic agents survival patients gallbladder carcinoma factors may affect survival examined method files 74 patients followed 2004 2013 retrospectively reviewed stage iii gallbladder carcinoma patients included study results median age 65 36 82 years 55 74 4 patients female stage determined 12 16 2 patients whereas stage ii iii determined 62 83 8 patients patients undergone surgical intervention positive surgical margin present 21 28 4 patients 14 58 4 patients re operated thirty nine 52 7 patients received chemotherapy combination cisplatin fluorouracil commonly used chemotherapy regimen received 15 38 5 patients radiotherapy alone performed none patients 8 10 8 patients received chemoradiotherapy whereas dfs 21 1 7 17 2 24 9 95 ci adjuvant therapy arm os found 24 2 05 19 9 28 9 95 ci dfs 23 6 7 9 7 36 3 95 ci os 28 2 8 22 5 33 5 95 ci patients receive adjuvant therapy differences dfs p 0 246 os statistically significant p 0 534 effectiveness adjuvant therapy dfs os subgroups surgical margin positivity stage ii patients older 65 years old statistically significant conclusion standard adjuvant therapy gallbladder carcinoma present study demonstrated favorable effect adjuvant therapy particularly selected patients prospective studies large patient groups needed clarify benefits adjuvant therapy google scholar","probabilities":0.9799733,"Title":"Adjuvant Therapy In Patients With Gallbladder Carcinoma","Abstract":"AIM: This study aimed to investigate the effects of adjuvant therapy and chemotherapeutic agents on survival of patients with gallbladder carcinoma. Factors that may affect survival were examined. METHOD: The files of 74 patients who had been followed between 2004 and 2013 were retrospectively reviewed. Only stage I-III gallbladder carcinoma patients were included in the study. RESULTS: The median age was 65 (36-82) years and 55 (74.4%) of the patients were female. Stage I was determined in 12 (16.2%) patients, whereas Stage II and III were determined in 62 (83.8%) patients. All of the patients had undergone surgical intervention. Positive surgical margin was present in 21 (28.4%) patients and 14 (58.4%) of these patients were re-operated. Thirty-nine (52.7%) patients received chemotherapy. The combination of cisplatin-fluorouracil was the most commonly used chemotherapy regimen, received by 15 (38.5%) patients. Radiotherapy alone was performed in none of the patients, while 8 (10.8%) patients received chemoradiotherapy. Whereas DFS was 21±1.7 (17.2-24.9 95% CI) in the adjuvant therapy arm, OS was found to be 24±2.05 (19.9-28.9 95% CI). DFS was 23±6.7 (9.7-36.3 95% CI) and OS was 28±2.8 (22.5-33.5 95% CI) in the patients that did not receive adjuvant therapy. The differences in both DFS (p=0.246) and OS were not statistically significant (p=0.534). The effectiveness of adjuvant therapy on DFS and OS in the subgroups (surgical margin positivity, stage II patients, older than 65 years old) was statistically significant. CONCLUSION: There is no standard adjuvant therapy for gallbladder carcinoma. The present study demonstrated the favorable effect of adjuvant therapy, particularly for selected patients. Prospective studies in large patient groups are needed to clarify the benefits of adjuvant therapy.","Source":"Google Scholar","category":"HUMAN","training_data":"Adjuvant Therapy In Patients With Gallbladder Carcinoma AIM: This study aimed to investigate the effects of adjuvant therapy and chemotherapeutic agents on survival of patients with gallbladder carcinoma. Factors that may affect survival were examined. METHOD: The files of 74 patients who had been followed between 2004 and 2013 were retrospectively reviewed. Only stage I-III gallbladder carcinoma patients were included in the study. RESULTS: The median age was 65 (36-82) years and 55 (74.4%) of the patients were female. Stage I was determined in 12 (16.2%) patients, whereas Stage II and III were determined in 62 (83.8%) patients. All of the patients had undergone surgical intervention. Positive surgical margin was present in 21 (28.4%) patients and 14 (58.4%) of these patients were re-operated. Thirty-nine (52.7%) patients received chemotherapy. The combination of cisplatin-fluorouracil was the most commonly used chemotherapy regimen, received by 15 (38.5%) patients. Radiotherapy alone was performed in none of the patients, while 8 (10.8%) patients received chemoradiotherapy. Whereas DFS was 21±1.7 (17.2-24.9 95% CI) in the adjuvant therapy arm, OS was found to be 24±2.05 (19.9-28.9 95% CI). DFS was 23±6.7 (9.7-36.3 95% CI) and OS was 28±2.8 (22.5-33.5 95% CI) in the patients that did not receive adjuvant therapy. The differences in both DFS (p=0.246) and OS were not statistically significant (p=0.534). The effectiveness of adjuvant therapy on DFS and OS in the subgroups (surgical margin positivity, stage II patients, older than 65 years old) was statistically significant. CONCLUSION: There is no standard adjuvant therapy for gallbladder carcinoma. The present study demonstrated the favorable effect of adjuvant therapy, particularly for selected patients. Prospective studies in large patient groups are needed to clarify the benefits of adjuvant therapy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"enhancer zeste homolog 2 ezh2 promotes progression cholangiocarcinoma cells regulating cell cycle apoptosis background enhancer zeste homolog 2 ezh2 catalytic subunit polycomb repressive complex 2 prc2 present prc2 ezh2 catalyzes trimethylation lysine 27 residue histone h3 resulting epigenetic silencing gene expression cancer progression investigated expression function ezh2 intrahepatic extrahepatic cholangiocarcinoma icc ecc methods influence ezh2 cell growth apoptosis assessed knockdown experiments target gene ezh2 searched quantitative rt pcr clinical significance ezh2 86 cholangiocarcinoma patients 45 icc 41 ecc underwent curative surgery examined immunohistochemistry results vitro analysis knockdown ezh2 reduced cell growth induced g1 arrest induced apoptosis confirmed annexin v staining increased sub g1 populations cholangiocarcinoma cell lines expression levels p16 ink4a p27 kip1 remarkably increased knockdown ezh2 cell lines immunohistochemical study ezh2 upregulation correlated tumor diameter p 0 0103 icc lymph node metastasis p 0 0292 ecc ki67 index icc p 0 0364 ecc p 0 0017 addition ezh2 expression correlated poor prognosis icc p 0 0447 ecc p 0 0227 conclusions current study demonstrated relationships ezh2 expression acceleration cell cycle antiapoptosis poor prognosis cholangiocarcinoma results suggest ezh2 may represent potential therapeutic target patients cholangiocarcinoma pubmed","probabilities":0.875,"Title":"Enhancer of zeste homolog 2 (EZH2) promotes progression of cholangiocarcinoma cells by regulating cell cycle and apoptosis","Abstract":"BACKGROUND: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2). When present in PRC2, EZH2 catalyzes trimethylation on lysine 27 residue of histone H3, resulting in epigenetic silencing of gene expression and cancer progression. We investigated the expression and function of EZH2 in intrahepatic and extrahepatic cholangiocarcinoma (ICC and ECC). METHODS: The influence of EZH2 on cell growth and apoptosis was assessed by knockdown experiments. Target gene of EZH2 was searched by quantitative RT-PCR. Clinical significance of EZH2 in 86 cholangiocarcinoma patients (45 ICC and 41 ECC) who underwent curative surgery was examined by immunohistochemistry. RESULTS: In vitro analysis, knockdown of EZH2 reduced cell growth, induced G1 arrest, and induced apoptosis, as confirmed by Annexin V staining and increased sub-G1 populations in cholangiocarcinoma cell lines. The expression levels of p16 (INK4a) and p27 (KIP1) were remarkably increased by knockdown of EZH2 in these cell lines. In immunohistochemical study, EZH2 upregulation correlated with tumor diameter (p = 0.0103) in ICC, lymph node metastasis (p = 0.0292) in ECC, and Ki67 index in both ICC (p = 0.0364) and ECC (p = 0.0017). In addition, EZH2 expression was correlated with poor prognosis in both ICC (p = 0.0447) and ECC (p = 0.0227). CONCLUSIONS: The current study demonstrated relationships between EZH2 expression and acceleration of the cell cycle and antiapoptosis, and poor prognosis in cholangiocarcinoma. These results suggest that EZH2 may represent a potential therapeutic target in patients with cholangiocarcinoma.","Source":"PubMed","category":"ANIMAL","training_data":"Enhancer of zeste homolog 2 (EZH2) promotes progression of cholangiocarcinoma cells by regulating cell cycle and apoptosis BACKGROUND: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2). When present in PRC2, EZH2 catalyzes trimethylation on lysine 27 residue of histone H3, resulting in epigenetic silencing of gene expression and cancer progression. We investigated the expression and function of EZH2 in intrahepatic and extrahepatic cholangiocarcinoma (ICC and ECC). METHODS: The influence of EZH2 on cell growth and apoptosis was assessed by knockdown experiments. Target gene of EZH2 was searched by quantitative RT-PCR. Clinical significance of EZH2 in 86 cholangiocarcinoma patients (45 ICC and 41 ECC) who underwent curative surgery was examined by immunohistochemistry. RESULTS: In vitro analysis, knockdown of EZH2 reduced cell growth, induced G1 arrest, and induced apoptosis, as confirmed by Annexin V staining and increased sub-G1 populations in cholangiocarcinoma cell lines. The expression levels of p16 (INK4a) and p27 (KIP1) were remarkably increased by knockdown of EZH2 in these cell lines. In immunohistochemical study, EZH2 upregulation correlated with tumor diameter (p = 0.0103) in ICC, lymph node metastasis (p = 0.0292) in ECC, and Ki67 index in both ICC (p = 0.0364) and ECC (p = 0.0017). In addition, EZH2 expression was correlated with poor prognosis in both ICC (p = 0.0447) and ECC (p = 0.0227). CONCLUSIONS: The current study demonstrated relationships between EZH2 expression and acceleration of the cell cycle and antiapoptosis, and poor prognosis in cholangiocarcinoma. These results suggest that EZH2 may represent a potential therapeutic target in patients with cholangiocarcinoma. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"altered expression oxidative metabolism related genes cholangiocarcinomas cholangiocarcinoma cca rare highly fatal cancer molecular mechanisms diagnostic markers obscure therefore investigated kinetic expression isocitrate dehydrogenase 1 idh1 isocitrate dehydrogenase 2 idh2 homogentisate 1 2 dioxygenase hgd tumorigenesis o viverrini infection associated cca animal model confirmed regulation expression human cases opisthorchiasis associated cca real time pcr kinetic expression hgd idh1 idh2 animal model o viverrini infection induced cca correlated human cca cases animal model expression hgd decreased time points p 0 01 expression idh1 idh2 decreased cca group human cases expression hgd idh1 idh2 decreased 2 fold 55 cases 70 5 25 cases 32 1 24 cases 30 8 respectively present study suggests reduction hgd idh1 idh2 may involve cholangiocarcinoma genesis may useful molecular diagnosis stn","probabilities":1.0,"Title":"Altered Expression Of Oxidative Metabolism Related Genes In Cholangiocarcinomas","Abstract":"Cholangiocarcinoma (CCA) is a rare but highly fatal cancer for which the molecular mechanisms and diagnostic markers are obscure. We therefore investigated the kinetic expression of isocitrate dehydrogenase-1 (IDH1), isocitrate dehydrogenase-2 (IDH2) and homogentisate 1,2-dioxygenase (HGD) during the tumorigenesis of O. viverrini infection-associated CCA in an animal model, and confirmed down-regulation of expression in human cases of opisthorchiasis-associated CCA through real time PCR. Kinetic expression of HGD, IDH1 and IDH2 in the animal model of O. viverrini infection-induced CCA was correlated with human CCA cases. In the animal model, expression of HGD was decreased at all time points (p<0.01) and expression of both IDH1 and IDH2 was decreased in the CCA group. In human cases, expression of HGD, IDH1 and IDH2 was decreased more than 2 fold in 55 cases (70.5%), 25 cases (32.1%) and 24 cases (30.8%) respectively. The present study suggests that reduction of HGD, IDH1 and IDH2 may be involve in cholangiocarcinoma genesis and may be useful for molecular diagnosis.","Source":"STN","category":"ANIMAL","training_data":"Altered Expression Of Oxidative Metabolism Related Genes In Cholangiocarcinomas Cholangiocarcinoma (CCA) is a rare but highly fatal cancer for which the molecular mechanisms and diagnostic markers are obscure. We therefore investigated the kinetic expression of isocitrate dehydrogenase-1 (IDH1), isocitrate dehydrogenase-2 (IDH2) and homogentisate 1,2-dioxygenase (HGD) during the tumorigenesis of O. viverrini infection-associated CCA in an animal model, and confirmed down-regulation of expression in human cases of opisthorchiasis-associated CCA through real time PCR. Kinetic expression of HGD, IDH1 and IDH2 in the animal model of O. viverrini infection-induced CCA was correlated with human CCA cases. In the animal model, expression of HGD was decreased at all time points (p<0.01) and expression of both IDH1 and IDH2 was decreased in the CCA group. In human cases, expression of HGD, IDH1 and IDH2 was decreased more than 2 fold in 55 cases (70.5%), 25 cases (32.1%) and 24 cases (30.8%) respectively. The present study suggests that reduction of HGD, IDH1 and IDH2 may be involve in cholangiocarcinoma genesis and may be useful for molecular diagnosis. STN","prediction_labels":"ANIMAL"},{"cleaned":"long term outcomes patients intraductal growth sub type intrahepatic cholangiocarcinoma background intraductal growth ig type intrahepatic cholangiocarcinoma icc may associated favorable prognosis compared mass forming mf periductal infiltrating pi icc methods clinico pathological characteristics long term outcomes 1206 patients undergoing liver resection icc compared based icc morphological classification results compared mf patients ig patients higher incidence poor un differentiated tumor lympho vascular perineural invasion poor un differentiated mf 18 vs ig 24 lympho vascular invasion mf 30 vs ig 35 perineural invasion mf 17 vs ig 33 p 0 05 pattern recurrence different among mf patients intrahepatic 63 extrahepatic 22 intra extrahepatic 16 versus ig patients intrahepatic 46 extrahepatic 25 intra extrahepatic 29 p 0 001 moreover 78 patients mf early recurrence 18 months surgery 59 ig patients early recurrence p 0 039 multivariable analysis controlling competing risk factors ig patients similar prognosis mf patients hr 0 90 p 0 69 conclusion ig patients frequently presented adverse pathological characteristics prognosis ig patients comparable mf patients controlling adverse factors pubmed","probabilities":0.9799733,"Title":"Long-term outcomes of patients with intraductal growth sub-type of intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Intraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC) may be associated with a favorable prognosis compared with mass-forming (MF) and periductal-infiltrating (PI) ICC. METHODS: The clinico-pathological characteristics and long-term outcomes of 1206 patients undergoing liver resection for ICC were compared based on the ICC morphological classification. RESULTS: Compared with MF patients, IG patients had a higher incidence of poor/un-differentiated tumor, lympho-vascular, and perineural invasion (poor/un-differentiated: MF, 18% vs. IG, 24%; lympho-vascular invasion: MF, 30% vs. IG, 35%; perineural invasion: MF, 17% vs. IG, 33%; all p > 0.05). The pattern of recurrence was different among MF patients (intrahepatic only: 63%; extrahepatic only: 22%; both intra- and extrahepatic: 16%) versus IG patients (intrahepatic only: 46%; extrahepatic: 25%; both intra- and extrahepatic: 29%) (p < 0.001). Moreover, while 78% of patients with MF had an early recurrence (<18 months from surgery), 59% of IG patients had and early recurrence (p = 0.039). On multivariable analysis, after controlling for competing risk factors, IG patients had a similar prognosis as MF patients (HR 0.90, p = 0.69). CONCLUSION: While IG patients more frequently presented with more adverse pathological characteristics, the prognosis of IG patients was comparable with MF patients after controlling for all these adverse factors.","Source":"PubMed","category":"HUMAN","training_data":"Long-term outcomes of patients with intraductal growth sub-type of intrahepatic cholangiocarcinoma BACKGROUND: Intraductal-growth (IG) type of intrahepatic cholangiocarcinoma (ICC) may be associated with a favorable prognosis compared with mass-forming (MF) and periductal-infiltrating (PI) ICC. METHODS: The clinico-pathological characteristics and long-term outcomes of 1206 patients undergoing liver resection for ICC were compared based on the ICC morphological classification. RESULTS: Compared with MF patients, IG patients had a higher incidence of poor/un-differentiated tumor, lympho-vascular, and perineural invasion (poor/un-differentiated: MF, 18% vs. IG, 24%; lympho-vascular invasion: MF, 30% vs. IG, 35%; perineural invasion: MF, 17% vs. IG, 33%; all p > 0.05). The pattern of recurrence was different among MF patients (intrahepatic only: 63%; extrahepatic only: 22%; both intra- and extrahepatic: 16%) versus IG patients (intrahepatic only: 46%; extrahepatic: 25%; both intra- and extrahepatic: 29%) (p < 0.001). Moreover, while 78% of patients with MF had an early recurrence (<18 months from surgery), 59% of IG patients had and early recurrence (p = 0.039). On multivariable analysis, after controlling for competing risk factors, IG patients had a similar prognosis as MF patients (HR 0.90, p = 0.69). CONCLUSION: While IG patients more frequently presented with more adverse pathological characteristics, the prognosis of IG patients was comparable with MF patients after controlling for all these adverse factors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic score recurrence whipple pancreaticoduodenectomy ampullary carcinomas results ageo retrospective multicenter cohort background ampullary carcinoma ac relatively rare entity often managed biliopancreatic carcinoma ac better prognosis peri ampullary tumors resection third patients relapse factors predictive recurrence controversial mainly relevant studies small also included non ac tumors guidelines use adjuvant neoadjuvant chemotherapy aim study identify prognostic factors recurrence ac resection large multicentric cohort establish simple practical predictive score recurrence order guide multidisciplinary decisions methods included 152 consecutive patients underwent whipple pancreaticoduodenectomy ampullary carcinoma january 2000 december 2010 10 gastrointestinal oncology departments results estimated overall 5 year disease free survival rate dfs 47 1 multivariate analysis age 75 years diagnosis p 0 0001 poor general condition p 0 01 poorly p 0 005 moderately differentiated tumors p 0 01 tnm stage iib iii p 0 05 associated poor dfs based multivariate analysis developed prognostic score three levels risk dfs 5 years 73 5 low risk group 20 1 high risk group conclusion simple score based age general condition tumor differentiation tnm stage classify patients subgroups different risks recurrence help therapeutic decisionmaking pubmed","probabilities":0.9799733,"Title":"Prognostic score for recurrence after Whipple's pancreaticoduodenectomy for ampullary carcinomas; results of an AGEO retrospective multicenter cohort","Abstract":"BACKGROUND: Ampullary carcinoma (AC) is a relatively rare entity often managed as a biliopancreatic carcinoma. AC has a better prognosis than peri ampullary tumors after resection, but more than a third of patients relapse. Factors predictive of recurrence are controversial, mainly because the relevant studies are very small or also included non AC tumors. There are no guidelines on the use of adjuvant or neoadjuvant chemotherapy. The aim of this study was to identify prognostic factors for recurrence after AC resection in a large multicentric cohort, and to establish a simple, practical, predictive score for recurrence in order to guide multidisciplinary decisions. METHODS: We included 152 consecutive patients who underwent Whipple's pancreaticoduodenectomy for ampullary carcinoma from January 2000 to December 2010 in 10 gastrointestinal oncology departments. RESULTS: The estimated overall 5-year disease-free survival rate (DFS) was 47.1%. In multivariate analysis, age≥ 75 years at diagnosis (p < 0.0001), poor general condition (p = 0.01), poorly (p = 0.005) or moderately differentiated tumors (p = 0.01) and TNM stage IIb or III (p = 0.05) were associated with poor DFS. Based on this multivariate analysis, we developed a prognostic score with three levels of risk: DFS at 5 years was 73.5% in the low-risk group and 20.1% in the high-risk group. CONCLUSION: This simple score based on age, general condition, tumor differentiation and TNM stage can classify patients into subgroups with different risks of recurrence and could help with therapeutic decisionmaking.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic score for recurrence after Whipple's pancreaticoduodenectomy for ampullary carcinomas; results of an AGEO retrospective multicenter cohort BACKGROUND: Ampullary carcinoma (AC) is a relatively rare entity often managed as a biliopancreatic carcinoma. AC has a better prognosis than peri ampullary tumors after resection, but more than a third of patients relapse. Factors predictive of recurrence are controversial, mainly because the relevant studies are very small or also included non AC tumors. There are no guidelines on the use of adjuvant or neoadjuvant chemotherapy. The aim of this study was to identify prognostic factors for recurrence after AC resection in a large multicentric cohort, and to establish a simple, practical, predictive score for recurrence in order to guide multidisciplinary decisions. METHODS: We included 152 consecutive patients who underwent Whipple's pancreaticoduodenectomy for ampullary carcinoma from January 2000 to December 2010 in 10 gastrointestinal oncology departments. RESULTS: The estimated overall 5-year disease-free survival rate (DFS) was 47.1%. In multivariate analysis, age≥ 75 years at diagnosis (p < 0.0001), poor general condition (p = 0.01), poorly (p = 0.005) or moderately differentiated tumors (p = 0.01) and TNM stage IIb or III (p = 0.05) were associated with poor DFS. Based on this multivariate analysis, we developed a prognostic score with three levels of risk: DFS at 5 years was 73.5% in the low-risk group and 20.1% in the high-risk group. CONCLUSION: This simple score based on age, general condition, tumor differentiation and TNM stage can classify patients into subgroups with different risks of recurrence and could help with therapeutic decisionmaking. PubMed","prediction_labels":"HUMAN"},{"cleaned":"efficacy sequential treatment strategy gemox followed folfiri advanced cholangiocarcinoma background gemcitabine gem platinum chemotherapy stands first line therapy patients recurrent advanced biliary tract cancer btc yielding progression free survival pfs 3 4 6 4 months standard second line chemotherapy gem platinum failure exists data survival benefit remain limited material methods retrospectively reviewed patients recurrent advanced btc received gemcitabine oxaliplatin gemox based chemotherapy followed 5 fluorouracil irinotecan folfiri based chemotherapy evaluate efficacy sequential treatment strategy overall survival os pfs calculated kaplan meier method results fifty two patients analyzed 21 40 intrahepatic 14 27 hilar extrahepatic 17 33 gallbladder cancer median age 64 years range 38 79 years prior curative intent resection primary tumor performed 23 44 2 patients gemox adjuvant chemotherapy given 12 23 1 patients median follow 36 3 months 47 90 4 patients completed treatment strategy first sequence gemox second sequence folfiri achieved 4 8 months 3 2 months median pfs respectively global os sequential chemotherapy 21 9 months sequence folfiri resulted median os 8 4 months conclusion sequence gemox folfiri potential treatment strategy patients recurrent advanced btc google scholar","probabilities":0.9799733,"Title":"Efficacy Of A Sequential Treatment Strategy With Gemox Followed By Folfiri In Advanced Cholangiocarcinoma","Abstract":"Background: Gemcitabine (GEM)-platinum chemotherapy stands as first-line therapy for patients with recurrent/advanced biliary tract cancer (BTC), yielding progression-free survival (PFS) of 3.4–6.4 months. No standard second-line chemotherapy after GEM-platinum failure exists and data on survival benefit remain limited. Material and methods: We retrospectively reviewed patients with recurrent/advanced BTC who received gemcitabine-oxaliplatin (GEMOX)-based chemotherapy followed by 5-fluorouracil-irinotecan (FOLFIRI)-based chemotherapy to evaluate the efficacy of the sequential treatment strategy. Overall survival (OS) and PFS were calculated by Kaplan–Meier method. Results: Fifty-two patients were analyzed, 21 (40%) had intrahepatic, 14 (27%) had hilar/extrahepatic, and 17 (33%) had gallbladder cancer. Median age was 64 years (range 38–79 years). Prior curative intent resection of the primary tumor was performed in 23 (44.2%) patients and GEMOX adjuvant chemotherapy was given in 12 (23.1%) patients. After a median follow-up of 36.3 months, 47 (90.4%) patients completed the treatment strategy. First-sequence GEMOX and second sequence FOLFIRI achieved 4.8 months and 3.2 months median PFS, respectively. The global OS for the sequential chemotherapy was 21.9 months. The sequence of FOLFIRI resulted in a median OS of 8.4 months. Conclusion: The sequence of GEMOX-FOLFIRI is a potential treatment strategy for patients with recurrent/advanced BTC.","Source":"Google Scholar","category":"HUMAN","training_data":"Efficacy Of A Sequential Treatment Strategy With Gemox Followed By Folfiri In Advanced Cholangiocarcinoma Background: Gemcitabine (GEM)-platinum chemotherapy stands as first-line therapy for patients with recurrent/advanced biliary tract cancer (BTC), yielding progression-free survival (PFS) of 3.4–6.4 months. No standard second-line chemotherapy after GEM-platinum failure exists and data on survival benefit remain limited. Material and methods: We retrospectively reviewed patients with recurrent/advanced BTC who received gemcitabine-oxaliplatin (GEMOX)-based chemotherapy followed by 5-fluorouracil-irinotecan (FOLFIRI)-based chemotherapy to evaluate the efficacy of the sequential treatment strategy. Overall survival (OS) and PFS were calculated by Kaplan–Meier method. Results: Fifty-two patients were analyzed, 21 (40%) had intrahepatic, 14 (27%) had hilar/extrahepatic, and 17 (33%) had gallbladder cancer. Median age was 64 years (range 38–79 years). Prior curative intent resection of the primary tumor was performed in 23 (44.2%) patients and GEMOX adjuvant chemotherapy was given in 12 (23.1%) patients. After a median follow-up of 36.3 months, 47 (90.4%) patients completed the treatment strategy. First-sequence GEMOX and second sequence FOLFIRI achieved 4.8 months and 3.2 months median PFS, respectively. The global OS for the sequential chemotherapy was 21.9 months. The sequence of FOLFIRI resulted in a median OS of 8.4 months. Conclusion: The sequence of GEMOX-FOLFIRI is a potential treatment strategy for patients with recurrent/advanced BTC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"bax mediated mechanism obatoclax induced apoptosis cholangiocarcinoma cells apoptosis induction bh3 mimetics therapeutic strategy human cancer mimetics exert single agent activity cells primed cell death primed cells dependent upon antiapoptotic bcl 2 proteins survival characterized ability bh3 mimetic induce cytochrome c release isolated mitochondria aim examine single agent activity obatoclax bh3 mimetic cholangiocarcinoma cell lines clonogenic assays inhibition colony formation observed obatoclax treatment despite single agent activity obatoclax mitochondria cells release cytochrome c incubation bh3 mimetic however immunofluorescence cell fractionation studies identified bax activation translocation mitochondria treatment obatoclax shrna targeted knockdown bax doubled ic50 obatoclax abrogate cytotoxicity whereas knockdown bak alter ic50 cell free system obatoclax induced activating conformational change bax attenuated site directed mutagenesis previously identified protein activation site finally drug also elicited significant vivo response rodent model disease conclusion single agent obatoclax treatment results bax activation contributes part cell death cholangiocarcinoma cells data indicate bh3 mimetics may also function direct activators bax induce cytotoxicity cells otherwise primed cell death stn","probabilities":0.9467213,"Title":"A Bax-Mediated Mechanism For Obatoclax-Induced Apoptosis Of Cholangiocarcinoma Cells","Abstract":"Apoptosis induction by BH3 mimetics is a therapeutic strategy for human cancer. These mimetics exert single-agent activity in cells \"primed\" for cell death. Primed cells are dependent upon antiapoptotic Bcl-2 proteins for survival and are characterized by the ability of the BH3 mimetic to induce cytochrome c release from their isolated mitochondria. Our aim was to examine the single-agent activity of obatoclax, a BH3 mimetic in cholangiocarcinoma cell lines. In clonogenic assays, inhibition of colony formation was observed by obatoclax treatment. Despite single-agent activity by obatoclax, the mitochondria from these cells did not release cytochrome c after incubation with this BH3 mimetic. However, immunofluorescence and cell fractionation studies identified Bax activation and translocation to mitochondria after treatment with obatoclax. shRNA targeted knockdown of Bax doubled the IC50 for obatoclax but did not abrogate its cytotoxicity, whereas knockdown of Bak did not alter the IC50. In a cell-free system, obatoclax induced an activating conformational change of Bax, which was attenuated by a site-directed mutagenesis of a previously identified protein activation site. Finally, the drug also elicited a significant in vivo response in a rodent model of this disease. In conclusion, single-agent obatoclax treatment results in Bax activation, which contributes, in part, to cell death in cholangiocarcinoma cells. These data indicate that BH3 mimetics may also function as direct activators of Bax and induce cytotoxicity in cells not otherwise primed for cell death.","Source":"STN","category":"ANIMAL","training_data":"A Bax-Mediated Mechanism For Obatoclax-Induced Apoptosis Of Cholangiocarcinoma Cells Apoptosis induction by BH3 mimetics is a therapeutic strategy for human cancer. These mimetics exert single-agent activity in cells \"primed\" for cell death. Primed cells are dependent upon antiapoptotic Bcl-2 proteins for survival and are characterized by the ability of the BH3 mimetic to induce cytochrome c release from their isolated mitochondria. Our aim was to examine the single-agent activity of obatoclax, a BH3 mimetic in cholangiocarcinoma cell lines. In clonogenic assays, inhibition of colony formation was observed by obatoclax treatment. Despite single-agent activity by obatoclax, the mitochondria from these cells did not release cytochrome c after incubation with this BH3 mimetic. However, immunofluorescence and cell fractionation studies identified Bax activation and translocation to mitochondria after treatment with obatoclax. shRNA targeted knockdown of Bax doubled the IC50 for obatoclax but did not abrogate its cytotoxicity, whereas knockdown of Bak did not alter the IC50. In a cell-free system, obatoclax induced an activating conformational change of Bax, which was attenuated by a site-directed mutagenesis of a previously identified protein activation site. Finally, the drug also elicited a significant in vivo response in a rodent model of this disease. In conclusion, single-agent obatoclax treatment results in Bax activation, which contributes, in part, to cell death in cholangiocarcinoma cells. These data indicate that BH3 mimetics may also function as direct activators of Bax and induce cytotoxicity in cells not otherwise primed for cell death. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic value preoperative serum carcinoembryonic antigen carbohydrate antigen 19 9 resection ampullary cancer background purpose study investigate prognostic value pre resection serum carcinoembryonic antigen cea carbohydrate antigen ca 19 9 resection ampullary cancer ac consideration intestinal pancreatobiliary pt subtypes methods overall survival os analysis patients undergoing curative resection ampullary cancer results elevated preoperative cea p 0 013 ca 19 9 levels p 0 030 significant prognostic factors subgroup analysis however showed markers prognostic value subgroup pre resection cea within normal range identified subgroup patients excellent median survival 145 months compared ac patients low risk cea subpopulation characterized less frequent advanced pt stages pt3 pt4 41 vs 62 p 0 047 lymph node involvement pn 30 vs 65 p 0 001 os subgroup significantly better compared ac patients 145 vs 25 months hr 3 8 p 0 001 multivariate survival analysis patient age pt subtype elevated pre resection serum cea value identified independent prognostic variables conclusions ac histomorphologic subclassification highly relevant regarding prognostic value preoperative serum cea ca 19 9 patients normal preoperative cea represent favorable subgroup excellent long term survival pubmed","probabilities":0.9799733,"Title":"Prognostic Value of Preoperative Serum Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 After Resection of Ampullary Cancer","Abstract":"BACKGROUND: The purpose of this study is to investigate the prognostic value of pre-resection serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 after resection of ampullary cancer (AC) in consideration of intestinal (IT) and pancreatobiliary (PT) subtypes. METHODS: Overall survival (OS) analysis of patients undergoing curative resection of ampullary cancer. RESULTS: Elevated preoperative CEA (P = 0.013) and CA 19-9 levels (P = 0.030) were significant prognostic factors. Subgroup analysis, however, showed both markers having prognostic value only for the IT subgroup. Pre-resection CEA within normal range identified a subgroup of IT patients with an excellent median survival of 145 months. Compared to other AC patients, this low-risk IT(CEA)(-) subpopulation was characterized by less frequent advanced pT stages (pT3/pT4, 41 vs. 62%; P = 0.047) and lymph node involvement (pN+, 30 vs. 65%; P = 0.001). OS of this subgroup was significantly better compared to other AC patients (145 vs. 25 months; HR = 3.8; P < 0.001). By multivariate survival analysis, the patient age, the PT subtype, and an elevated pre-resection serum CEA value were identified as independent prognostic variables. CONCLUSIONS: In AC, the histomorphologic subclassification is highly relevant regarding the prognostic value of preoperative serum CEA and CA 19-9. IT-patients with normal preoperative CEA represent a favorable subgroup with excellent long-term survival.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Value of Preoperative Serum Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 After Resection of Ampullary Cancer BACKGROUND: The purpose of this study is to investigate the prognostic value of pre-resection serum carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 after resection of ampullary cancer (AC) in consideration of intestinal (IT) and pancreatobiliary (PT) subtypes. METHODS: Overall survival (OS) analysis of patients undergoing curative resection of ampullary cancer. RESULTS: Elevated preoperative CEA (P = 0.013) and CA 19-9 levels (P = 0.030) were significant prognostic factors. Subgroup analysis, however, showed both markers having prognostic value only for the IT subgroup. Pre-resection CEA within normal range identified a subgroup of IT patients with an excellent median survival of 145 months. Compared to other AC patients, this low-risk IT(CEA)(-) subpopulation was characterized by less frequent advanced pT stages (pT3/pT4, 41 vs. 62%; P = 0.047) and lymph node involvement (pN+, 30 vs. 65%; P = 0.001). OS of this subgroup was significantly better compared to other AC patients (145 vs. 25 months; HR = 3.8; P < 0.001). By multivariate survival analysis, the patient age, the PT subtype, and an elevated pre-resection serum CEA value were identified as independent prognostic variables. CONCLUSIONS: In AC, the histomorphologic subclassification is highly relevant regarding the prognostic value of preoperative serum CEA and CA 19-9. IT-patients with normal preoperative CEA represent a favorable subgroup with excellent long-term survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"diversification trends biliary tree cancer among three major ethnic groups state new mexico background new mexico population composed 45 non hispanic whites 42 hispanics 10 american indians 3 minorities purpose study compare trends biliary tract cancer among groups past 3 decades methods state tumor registry used ascertain incidence gallbladder cancer extrahepatic bile duct cancer intrahepatic bile duct cancer results total 1 449 new biliary cancers diagnosed 1981 2008 contemporary incidence gallbladder cancer remains several times higher among american indians ethnicities men 4 1 1 1 8 american indians hispanics non hispanic whites respectively women 8 1 2 1 1 0 respectively conclusions biliary malignancies prevalent among american indians despite decline incidence gallbladder cancer among american indians hispanics remains higher compared state non hispanic white population stn","probabilities":0.9799733,"Title":"Diversification And Trends In Biliary Tree Cancer Among The Three Major Ethnic Groups In The State Of New Mexico","Abstract":"Background: New Mexico's population is composed of 45% non-Hispanic whites, 42% Hispanics, 10% American Indians, and 3% other minorities. The purpose of this study was to compare the trends of biliary tract cancer among these groups over the past 3 decades. \r\n\r\n Methods: The state's tumor registry was used to ascertain the incidence of gallbladder cancer, extrahepatic bile duct cancer, and intrahepatic bile duct cancer. \r\n\r\n Results: A total of 1,449 new biliary cancers were diagnosed between 1981 and 2008. The contemporary incidence of gallbladder cancer remains several times higher among American Indians than in other ethnicities: for men, 4.1%, 1.1%, and .8% for American Indians, Hispanics, and non-Hispanic whites, respectively, and for women, 8.1%, 2.1%, and 1.0%, respectively. \r\n\r\n Conclusions: Biliary malignancies are more prevalent among American Indians. Despite a decline in the incidence of gallbladder cancer among American Indians and Hispanics, it remains higher compared with the state's non-Hispanic white population.","Source":"STN","category":"HUMAN","training_data":"Diversification And Trends In Biliary Tree Cancer Among The Three Major Ethnic Groups In The State Of New Mexico Background: New Mexico's population is composed of 45% non-Hispanic whites, 42% Hispanics, 10% American Indians, and 3% other minorities. The purpose of this study was to compare the trends of biliary tract cancer among these groups over the past 3 decades. \r\n\r\n Methods: The state's tumor registry was used to ascertain the incidence of gallbladder cancer, extrahepatic bile duct cancer, and intrahepatic bile duct cancer. \r\n\r\n Results: A total of 1,449 new biliary cancers were diagnosed between 1981 and 2008. The contemporary incidence of gallbladder cancer remains several times higher among American Indians than in other ethnicities: for men, 4.1%, 1.1%, and .8% for American Indians, Hispanics, and non-Hispanic whites, respectively, and for women, 8.1%, 2.1%, and 1.0%, respectively. \r\n\r\n Conclusions: Biliary malignancies are more prevalent among American Indians. Despite a decline in the incidence of gallbladder cancer among American Indians and Hispanics, it remains higher compared with the state's non-Hispanic white population. STN","prediction_labels":"HUMAN"},{"cleaned":"hmga1 correlates metastasis short survival cholangiocarcinoma patients properly copy pasted go link click p 3118 google scholar","probabilities":0.9799733,"Title":"Hmga1 Correlates With Metastasis And Short Survival Of Cholangiocarcinoma Patients","Abstract":"Cannot be properly copy-pasted. Go through the link Click P-3118","Source":"Google Scholar","category":"HUMAN","training_data":"Hmga1 Correlates With Metastasis And Short Survival Of Cholangiocarcinoma Patients Cannot be properly copy-pasted. Go through the link Click P-3118 Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"major hepatectomy safe modality treatment intrahepatic cholangiocarcinoma selected patients complicated cirrhosis objective objective paper evaluate perioperative outcomes major hepatectomy intrahepatic cholangiocarcinoma icc patients cirrhosis methods retrospectively evaluated preoperative intraoperative postoperative findings 42 consecutive patients cirrhosis 102 patients normal livers underwent major hepatectomy icc results preoperative liver function worse patients cirrhosis compared patients without cirrhosis cirrhotic patients significantly higher intraoperative blood loss longer operation time longer hospital stay non cirrhotic patients however two groups similar overall morbidity hospital mortality rates similar rates liver failure complications r0 resection rates resection margin widths disease free survival rates also similar conclusions major hepatectomy icc performed selected cirrhotic patients acceptable morbidity mortality rates compared patients without cirrhosis pubmed","probabilities":0.9799733,"Title":"Major hepatectomy is a safe modality for the treatment of intrahepatic cholangiocarcinoma in selected patients complicated with cirrhosis","Abstract":"OBJECTIVE: The objective of this paper is to evaluate the perioperative outcomes of major hepatectomy for intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis. METHODS: We retrospectively evaluated the preoperative, intraoperative, and postoperative findings in 42 consecutive patients with cirrhosis and in 102 patients with normal livers who underwent major hepatectomy for ICC. RESULTS: Preoperative liver function was worse in patients with cirrhosis compared to patients without cirrhosis. Cirrhotic patients had significantly higher intraoperative blood loss, longer operation time, and longer hospital stay than non-cirrhotic patients. However, the two groups had similar overall morbidity and hospital mortality rates and similar rates of liver failure or other complications. Their R0 resection rates, resection margin widths and disease-free survival rates were also similar. CONCLUSIONS: Major hepatectomy for ICC can be performed in selected cirrhotic patients with acceptable morbidity and mortality rates, as compared to patients without cirrhosis.","Source":"PubMed","category":"HUMAN","training_data":"Major hepatectomy is a safe modality for the treatment of intrahepatic cholangiocarcinoma in selected patients complicated with cirrhosis OBJECTIVE: The objective of this paper is to evaluate the perioperative outcomes of major hepatectomy for intrahepatic cholangiocarcinoma (ICC) in patients with cirrhosis. METHODS: We retrospectively evaluated the preoperative, intraoperative, and postoperative findings in 42 consecutive patients with cirrhosis and in 102 patients with normal livers who underwent major hepatectomy for ICC. RESULTS: Preoperative liver function was worse in patients with cirrhosis compared to patients without cirrhosis. Cirrhotic patients had significantly higher intraoperative blood loss, longer operation time, and longer hospital stay than non-cirrhotic patients. However, the two groups had similar overall morbidity and hospital mortality rates and similar rates of liver failure or other complications. Their R0 resection rates, resection margin widths and disease-free survival rates were also similar. CONCLUSIONS: Major hepatectomy for ICC can be performed in selected cirrhotic patients with acceptable morbidity and mortality rates, as compared to patients without cirrhosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors gallbladder cancer report 53 cases although small cell carcinoma gallbladder rare prognosis tumor type poorer differentiated carcinomas report herein case 62 year old man small cell carcinoma gallbladder operative findings showed unresectable large tumor gallbladder multiple metastases involving liver lymph nodes pathological findings revealed small sized carcinoma cells round oval shape displayed cord like solid appearance diagnosis confirmed ultrastructural study showed presence neurosecretory type cored granules treated intraarterial chemotherapy cisplatin etoposide six months later abdominal computed tomography scan confirmed loss large mass complete response chemotherapy noted period six months suggesting efficacy intraarterial chemotherapy disease fifty three cases small cell carcinoma reported english literature reviewed cases including radical operation indicated prognosis extremely poor due difficulty early diagnosis rapid progression disease chemotherapy effective general intraarterial chemotherapy performed present case may particularly useful improve survival stn","probabilities":0.9467213,"Title":"Prognostic Factors Of Gallbladder Cancer: A Report Of 53 Cases","Abstract":"Although small cell carcinoma of the gallbladder is rare, the prognosis of this tumor type is poorer than that of differentiated carcinomas. We report herein the case of a 62-year-old man with small cell carcinoma of the gallbladder. The operative findings showed an unresectable large tumor of the gallbladder and multiple metastases involving the liver and lymph nodes. Pathological findings revealed small sized carcinoma cells, round or oval in shape which displayed a cord-like or solid appearance. Diagnosis was confirmed by ultrastructural study that showed the presence of neurosecretory-type cored granules. He was treated by intraarterial chemotherapy with cisplatin and etoposide. Six months later, abdominal computed tomography scan confirmed loss of the large mass. A complete response to the chemotherapy was noted over a period of six months, suggesting the efficacy of intraarterial chemotherapy for this disease. Fifty-three cases of small cell carcinoma reported in the English literature are reviewed. In most cases, including ours, a radical operation was not indicated and the prognosis was extremely poor, due to the difficulty of early diagnosis and the rapid progression of the disease. Chemotherapy is effective in general and intraarterial chemotherapy performed in the present case may be particularly useful to improve survival.","Source":"STN","category":"HUMAN","training_data":"Prognostic Factors Of Gallbladder Cancer: A Report Of 53 Cases Although small cell carcinoma of the gallbladder is rare, the prognosis of this tumor type is poorer than that of differentiated carcinomas. We report herein the case of a 62-year-old man with small cell carcinoma of the gallbladder. The operative findings showed an unresectable large tumor of the gallbladder and multiple metastases involving the liver and lymph nodes. Pathological findings revealed small sized carcinoma cells, round or oval in shape which displayed a cord-like or solid appearance. Diagnosis was confirmed by ultrastructural study that showed the presence of neurosecretory-type cored granules. He was treated by intraarterial chemotherapy with cisplatin and etoposide. Six months later, abdominal computed tomography scan confirmed loss of the large mass. A complete response to the chemotherapy was noted over a period of six months, suggesting the efficacy of intraarterial chemotherapy for this disease. Fifty-three cases of small cell carcinoma reported in the English literature are reviewed. In most cases, including ours, a radical operation was not indicated and the prognosis was extremely poor, due to the difficulty of early diagnosis and the rapid progression of the disease. Chemotherapy is effective in general and intraarterial chemotherapy performed in the present case may be particularly useful to improve survival. STN","prediction_labels":"ANIMAL"},{"cleaned":"long non coding rna linc itgb1 knockdown inhibits cell migration invasion gbc sd m gbc sd gallbladder cancer cell lines gallbladder cancer highly aggressive malignancy low 5 year survival rate despite advances molecular understanding initiation progression gallbladder cancer treatment modalities surgery radiotherapy chemotherapy advanced cases yield promising outcomes therefore great importance uncover new mechanism underlying gallbladder cancer growth metastasis study identified differentially expressed long intergenic non coding rna linc itgb1 pair higher lower metastatic gallbladder cancer cell sublines potential role linc itgb1 gallbladder cancer cell proliferation migration invasion explored using lentivirus mediated rna interference system functional analysis showed knockdown linc itgb1 significantly inhibited gallbladder cancer cell proliferation moreover cell migration invasion reduced twofold linc itgb1 knockdown cells probably due upregulation catenin downregulation vimentin slug tcf8 conclusion linc itgb1 potentially promoted gallbladder cancer invasion metastasis accelerating process epithelial mesenchymal transition application rna interference targeting linc itgb1 might potential form gallbladder cancer treatment advanced cases stn","probabilities":0.9467213,"Title":"Long Non-Coding Rna Linc-Itgb1 Knockdown Inhibits Cell Migration And Invasion In Gbc-Sd/M And Gbc-Sd Gallbladder Cancer Cell Lines","Abstract":"Gallbladder cancer is a highly aggressive malignancy with a low 5-year survival rate. Despite advances in the molecular understanding of the initiation and progression in gallbladder cancer, treatment modalities such as surgery, radiotherapy, or chemotherapy in advanced cases did not yield promising outcomes. Therefore, it is of great importance to uncover new mechanism underlying gallbladder cancer growth and metastasis. In this study, we identified a differentially expressed long intergenic non-coding RNA, linc-ITGB1, in a pair of higher and lower metastatic gallbladder cancer cell sublines. Then, the potential role of linc-ITGB1 in gallbladder cancer cell proliferation, migration, and invasion was explored using a lentivirus-mediated RNA interference system. Functional analysis showed that knockdown of linc-ITGB1 significantly inhibited gallbladder cancer cell proliferation. Moreover, cell migration and invasion were reduced by over twofold in linc-ITGB1 knockdown cells probably due to upregulation of β-catenin and downregulation of vimentin, slug, and TCF8. In conclusion, linc-ITGB1 potentially promoted gallbladder cancer invasion and metastasis by accelerating the process of epithelial-to-mesenchymal transition, and the application of RNA interference targeting linc-ITGB1 might be a potential form of gallbladder cancer treatment in advanced cases.","Source":"STN","category":"ANIMAL","training_data":"Long Non-Coding Rna Linc-Itgb1 Knockdown Inhibits Cell Migration And Invasion In Gbc-Sd/M And Gbc-Sd Gallbladder Cancer Cell Lines Gallbladder cancer is a highly aggressive malignancy with a low 5-year survival rate. Despite advances in the molecular understanding of the initiation and progression in gallbladder cancer, treatment modalities such as surgery, radiotherapy, or chemotherapy in advanced cases did not yield promising outcomes. Therefore, it is of great importance to uncover new mechanism underlying gallbladder cancer growth and metastasis. In this study, we identified a differentially expressed long intergenic non-coding RNA, linc-ITGB1, in a pair of higher and lower metastatic gallbladder cancer cell sublines. Then, the potential role of linc-ITGB1 in gallbladder cancer cell proliferation, migration, and invasion was explored using a lentivirus-mediated RNA interference system. Functional analysis showed that knockdown of linc-ITGB1 significantly inhibited gallbladder cancer cell proliferation. Moreover, cell migration and invasion were reduced by over twofold in linc-ITGB1 knockdown cells probably due to upregulation of β-catenin and downregulation of vimentin, slug, and TCF8. In conclusion, linc-ITGB1 potentially promoted gallbladder cancer invasion and metastasis by accelerating the process of epithelial-to-mesenchymal transition, and the application of RNA interference targeting linc-ITGB1 might be a potential form of gallbladder cancer treatment in advanced cases. STN","prediction_labels":"ANIMAL"},{"cleaned":"significance ceacam6 expression cholangiocarcinoma purpose study investigate clinicopathological biological significance human carcinoembryonic antigen related cell adhesion molecule 6 ceacam6 gene expression human intrahepatic cholangiocarcinoma ceacam6 reported involved human malignancies however cholangiocarcinoma expression ceacam6 clinicopathological significance investigated ceacam6 expression status determined analysed respect various clinicopathological parameters 23 intrahepatic cholangiocarcinomas additionally investigated effects ceacam6 gene cholangiocarcinoma cell lines ceacam6 gene expression cancer tissues higher noncancerous tissues 16 23 cases however statistically significant tumours elevated ceacam6 expression showed tendency associated lymphatic invasion stage disease interestingly patients high ceacam6 expression showed significantly poorer disease free survival rate low ceacam6 expression demonstrated ceacam6 transfected cells proliferative invasive chemoresistant gemcitabine compared mock transfected cells furthermore ceacam6 gene silencing ceacam6 specific sirna resulted higher chemosensitivity gemcitabine ceacam6 potential prognostic indicator potential chemoresistant marker gemcitabine patients intrahepatic cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Significance Of Ceacam6 Expression In Cholangiocarcinoma","Abstract":"The purpose of this study was to investigate the clinicopathological and biological significance of human carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) gene expression in human intrahepatic cholangiocarcinoma. CEACAM6 is reported to be involved in human malignancies. However, in cholangiocarcinoma expression of CEACAM6 and its clinicopathological significance have not been investigated. CEACAM6 expression status was determined and analysed with respect to various clinicopathological parameters in 23 intrahepatic cholangiocarcinomas. Additionally, we investigated effects of CEACAM6 gene in the cholangiocarcinoma cell lines. CEACAM6 gene expression in cancer tissues was higher than in noncancerous tissues in 16 of the 23 cases; however, it was not statistically significant. The tumours with elevated CEACAM6 expression showed a tendency to be associated with lymphatic invasion and stage of the disease. Interestingly, patients with high CEACAM6 expression showed a significantly poorer disease-free survival rate than those with low CEACAM6 expression. We demonstrated that CEACAM6-transfected cells were more proliferative, more invasive and more chemoresistant to gemcitabine compared to mock-transfected cells. Furthermore, CEACAM6 gene silencing by CEACAM6-specific siRNA resulted in higher chemosensitivity to gemcitabine. CEACAM6 is a potential prognostic indicator and potential chemoresistant marker to gemcitabine for patients with intrahepatic cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Significance Of Ceacam6 Expression In Cholangiocarcinoma The purpose of this study was to investigate the clinicopathological and biological significance of human carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6) gene expression in human intrahepatic cholangiocarcinoma. CEACAM6 is reported to be involved in human malignancies. However, in cholangiocarcinoma expression of CEACAM6 and its clinicopathological significance have not been investigated. CEACAM6 expression status was determined and analysed with respect to various clinicopathological parameters in 23 intrahepatic cholangiocarcinomas. Additionally, we investigated effects of CEACAM6 gene in the cholangiocarcinoma cell lines. CEACAM6 gene expression in cancer tissues was higher than in noncancerous tissues in 16 of the 23 cases; however, it was not statistically significant. The tumours with elevated CEACAM6 expression showed a tendency to be associated with lymphatic invasion and stage of the disease. Interestingly, patients with high CEACAM6 expression showed a significantly poorer disease-free survival rate than those with low CEACAM6 expression. We demonstrated that CEACAM6-transfected cells were more proliferative, more invasive and more chemoresistant to gemcitabine compared to mock-transfected cells. Furthermore, CEACAM6 gene silencing by CEACAM6-specific siRNA resulted in higher chemosensitivity to gemcitabine. CEACAM6 is a potential prognostic indicator and potential chemoresistant marker to gemcitabine for patients with intrahepatic cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"molecular pathogenesis cholangiocarcinoma become increasingly apparent late inflammation plays integral role spectrum malignancies including cholangiocarcinoma cca primary sclerosing cholangitis chronic inflammation common risk factor cca western world recent work highlighted inflammatory pathways essential carcinogenesis tissue invasion migration inflammation advances carcinogenesis induction dna damage evasion apoptosis promotion cell proliferation neoangiogenesis cca characterized presence desmoplastic stroma consisting cancer associated fibroblasts tumor associated macrophages tumor infiltrating lymphocytes rich inflammatory milieu vital cancer ecosystem targeting components represents attractive therapeutic option pubmed","probabilities":0.962963,"Title":"Molecular pathogenesis of cholangiocarcinoma","Abstract":"It has become increasingly apparent of late that inflammation plays an integral role in a spectrum of malignancies including cholangiocarcinoma (CCA). Primary sclerosing cholangitis with chronic inflammation is the most common risk factor for CCA in the Western world. Recent work has highlighted that inflammatory pathways are essential in carcinogenesis and tissue invasion and migration. Inflammation advances carcinogenesis by induction of DNA damage, evasion of apoptosis, promotion of cell proliferation, and neoangiogenesis. CCA is characterized by the presence of a desmoplastic stroma consisting of cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating lymphocytes. This rich inflammatory milieu is vital to the cancer ecosystem, and targeting its components represents an attractive therapeutic option.","Source":"PubMed","category":"HUMAN","training_data":"Molecular pathogenesis of cholangiocarcinoma It has become increasingly apparent of late that inflammation plays an integral role in a spectrum of malignancies including cholangiocarcinoma (CCA). Primary sclerosing cholangitis with chronic inflammation is the most common risk factor for CCA in the Western world. Recent work has highlighted that inflammatory pathways are essential in carcinogenesis and tissue invasion and migration. Inflammation advances carcinogenesis by induction of DNA damage, evasion of apoptosis, promotion of cell proliferation, and neoangiogenesis. CCA is characterized by the presence of a desmoplastic stroma consisting of cancer-associated fibroblasts, tumor-associated macrophages, and tumor-infiltrating lymphocytes. This rich inflammatory milieu is vital to the cancer ecosystem, and targeting its components represents an attractive therapeutic option. PubMed","prediction_labels":"HUMAN"},{"cleaned":"orthotopic liver transplantation combination neoadjuvant therapy new paradigm treatment unresectable intrahepatic cholangiocarcinoma purpose review surgical resection primary modality treatment hilar intrahepatic cholangiocarcinoma hcca icca unresectable early stage hcca excellent long term tumor recurrence free patient survival achieved using strict regimen preoperative staging neoadjuvant chemoradiation treatment followed orthotopic liver transplantation olt however case unresectable icca data outcomes olt limited present article reviews current literature surgical treatment icca focusing role olt combination neoadjuvant therapy risk stratification patients considered transplantation unresectable icca recent findings numerous studies reported poor survival outcomes olt icca recent data using combination neoadjuvant therapy followed olt appropriately selected patients unresectable icca demonstrated promising disease recurrence free survival summary risk stratification patient selection crucial optimize survival outcomes excellent long term disease recurrence free survival achieved selected patients unresectable icca using combination olt neoadjuvant therapy current data support expansion liver transplant criteria treatment unresectable icca pubmed","probabilities":0.9799733,"Title":"Orthotopic liver transplantation in combination with neoadjuvant therapy: a new paradigm in the treatment of unresectable intrahepatic cholangiocarcinoma","Abstract":"PURPOSE OF REVIEW: Surgical resection is the primary modality of treatment for hilar and intrahepatic cholangiocarcinoma (HCCA-ICCA). For unresectable early-stage HCCA, excellent long-term tumor recurrence-free patient survival has been achieved using a strict regimen of preoperative staging and neoadjuvant chemoradiation treatment followed by orthotopic liver transplantation (OLT). However, in the case of unresectable ICCA, data on outcomes after OLT are limited. The present article reviews the current literature on the surgical treatment of ICCA focusing on the role of OLT in combination with neoadjuvant therapy and risk stratification of patients being considered for transplantation for unresectable ICCA. RECENT FINDINGS: Numerous studies reported poor survival outcomes after OLT for ICCA. Recent data using a combination of neoadjuvant therapy followed by OLT in appropriately selected patients with unresectable ICCA demonstrated promising disease recurrence-free survival. SUMMARY: Risk stratification for patient selection is crucial to optimize survival outcomes. Excellent long-term disease recurrence-free survival can be achieved in selected patients with unresectable ICCA using a combination of OLT and neoadjuvant therapy. Current data support the expansion of liver transplant criteria for treatment of unresectable ICCA.","Source":"PubMed","category":"HUMAN","training_data":"Orthotopic liver transplantation in combination with neoadjuvant therapy: a new paradigm in the treatment of unresectable intrahepatic cholangiocarcinoma PURPOSE OF REVIEW: Surgical resection is the primary modality of treatment for hilar and intrahepatic cholangiocarcinoma (HCCA-ICCA). For unresectable early-stage HCCA, excellent long-term tumor recurrence-free patient survival has been achieved using a strict regimen of preoperative staging and neoadjuvant chemoradiation treatment followed by orthotopic liver transplantation (OLT). However, in the case of unresectable ICCA, data on outcomes after OLT are limited. The present article reviews the current literature on the surgical treatment of ICCA focusing on the role of OLT in combination with neoadjuvant therapy and risk stratification of patients being considered for transplantation for unresectable ICCA. RECENT FINDINGS: Numerous studies reported poor survival outcomes after OLT for ICCA. Recent data using a combination of neoadjuvant therapy followed by OLT in appropriately selected patients with unresectable ICCA demonstrated promising disease recurrence-free survival. SUMMARY: Risk stratification for patient selection is crucial to optimize survival outcomes. Excellent long-term disease recurrence-free survival can be achieved in selected patients with unresectable ICCA using a combination of OLT and neoadjuvant therapy. Current data support the expansion of liver transplant criteria for treatment of unresectable ICCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association wnt signaling pathway genetic variants gallbladder cancer susceptibility survival gallbladder cancer gbc common malignancy biliary tract adverse prognosis poor survival wnt signaling plays important role embryonic development regeneration tissues species deregulation expression mutations pathway may lead disease state cancer study assessed association common germline variants wnt pathway genes sfrp2 sfrp4 dkk2 dkk3 wisp3 apc catenin axin 2 gli 1 evaluate contribution predisposition gbc treatment outcomes study included 564 gbc patients 250 controls 564 200 patients followed treatment response survival tumor response recist 1 1 recorded 116 patients undergoing non adjuvant chemotherapy nact survival assessed kaplan meier curve cox proportional hazard regression single locus analysis showed significant association sfrp4 rs1802073g p value 0 0001 dkk2 rs17037102c p value 0 0001 dkk3 rs3206824c p value 0 012 apc rs4595552 p value 0 021 apc rs11954856g p value 0 047 axin 2 rs4791171c p value 0 001 catenin rs4135385a g p value 0 031 gli 1 rs222826c g p value 0 001 increased risk gbc gene gene interaction using gmdr analysis predicted apc rs11954856 axin2 rs4791171 significant conferring gbc susceptibility cox proportional hazard model showed gli 1 rs2228226 cg gg axin 2 rs4791171 tt genotype higher hazard ratio recursive partitioning axin 2 rs4791171 tt genotype showed higher mortality hazard studied genetic variants influence gbc susceptibility apc rs11954856 gli 1 rs2228226 axin 2 rs4791171 found associated poor survival advanced gbc patients pubmed","probabilities":1.0,"Title":"Association of Wnt signaling pathway genetic variants in gallbladder cancer susceptibility and survival","Abstract":"Gallbladder cancer (GBC) is the most common malignancy of the biliary tract with adverse prognosis and poor survival. Wnt signaling plays an important role in embryonic development and regeneration of tissues in all the species. Deregulation of expression and mutations in this pathway may lead to disease state such as cancer. In this study, we assessed the association of common germline variants of Wnt pathway genes (SFRP2, SFRP4, DKK2, DKK3, WISP3, APC, β-catenin, AXIN-2, GLI-1) to evaluate their contribution in predisposition to GBC and treatment outcomes. The study included 564 GBC patients and 250 controls. Out of 564, 200 patients were followed up for treatment response and survival. Tumor response (RECIST 1.1) was recorded in 116 patients undergoing non-adjuvant chemotherapy (NACT). Survival was assessed by Kaplan-Meier curve and Cox-proportional hazard regression. Single locus analysis showed significant association of SFRP4 rs1802073G > T [p value = 0.0001], DKK2 rs17037102C > T [p value = 0.0001], DKK3 rs3206824C > T [p value = 0.012], APC rs4595552 A/T [p value = 0.021], APC rs11954856G > T [p value = 0.047], AXIN-2 rs4791171C > T [p value = 0.001], β-catenin rs4135385A > G [p value = 0.031], and GLI-1 rs222826C > G [p value = 0.001] with increased risk of GBC. Gene-gene interaction using GMDR analysis predicted APC rs11954856 and AXIN2 rs4791171 as significant in conferring GBC susceptibility. Cox-proportional hazard model showed GLI-1 rs2228226 CG/GG and AXIN-2 rs4791171 TT genotype higher hazard ratio. In recursive partitioning, AXIN-2 rs4791171 TT genotype showed higher mortality and hazard. Most of studied genetic variants influence GBC susceptibility. APC rs11954856, GLI-1 rs2228226, and AXIN-2 rs4791171 were found to be associated with poor survival in advanced GBC patients.","Source":"PubMed","category":"HUMAN","training_data":"Association of Wnt signaling pathway genetic variants in gallbladder cancer susceptibility and survival Gallbladder cancer (GBC) is the most common malignancy of the biliary tract with adverse prognosis and poor survival. Wnt signaling plays an important role in embryonic development and regeneration of tissues in all the species. Deregulation of expression and mutations in this pathway may lead to disease state such as cancer. In this study, we assessed the association of common germline variants of Wnt pathway genes (SFRP2, SFRP4, DKK2, DKK3, WISP3, APC, β-catenin, AXIN-2, GLI-1) to evaluate their contribution in predisposition to GBC and treatment outcomes. The study included 564 GBC patients and 250 controls. Out of 564, 200 patients were followed up for treatment response and survival. Tumor response (RECIST 1.1) was recorded in 116 patients undergoing non-adjuvant chemotherapy (NACT). Survival was assessed by Kaplan-Meier curve and Cox-proportional hazard regression. Single locus analysis showed significant association of SFRP4 rs1802073G > T [p value = 0.0001], DKK2 rs17037102C > T [p value = 0.0001], DKK3 rs3206824C > T [p value = 0.012], APC rs4595552 A/T [p value = 0.021], APC rs11954856G > T [p value = 0.047], AXIN-2 rs4791171C > T [p value = 0.001], β-catenin rs4135385A > G [p value = 0.031], and GLI-1 rs222826C > G [p value = 0.001] with increased risk of GBC. Gene-gene interaction using GMDR analysis predicted APC rs11954856 and AXIN2 rs4791171 as significant in conferring GBC susceptibility. Cox-proportional hazard model showed GLI-1 rs2228226 CG/GG and AXIN-2 rs4791171 TT genotype higher hazard ratio. In recursive partitioning, AXIN-2 rs4791171 TT genotype showed higher mortality and hazard. Most of studied genetic variants influence GBC susceptibility. APC rs11954856, GLI-1 rs2228226, and AXIN-2 rs4791171 were found to be associated with poor survival in advanced GBC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathologic significance sox2 cd44 cd44v6 expression intrahepatic cholangiocarcinoma embryonic stem cells esc cancer stem cells csc capacity self renewal differentiation multiple cell lineages sox2 plays critical role esc shown participate carcinogenesis tumor progression many human cancers cd44 cd44v6 putative csc markers association tumor progression metastasis tumor relapse treatment demonstrated evaluated immunoexpression sox2 cd44 cd44v6 85 cases intrahepatic cholangiocarcinomas ihcc assessed prognostic significance sox2 expression showed significant association lymph node metastasis p 0 025 t4 stage p 0 046 worse overall survival p 0 047 greater expression sox2 observed ihcc poor differentiation vascular invasion stage iv without statistical significance p 0 05 cd44 expression showed association periductal infiltrative type p 0 034 poor differentiation p 0 012 vascular invasion p 0 009 cd44v6 expression evident patients stage iv p 0 019 results demonstrated sox2 expression associated aggressive behavior poor overall survival ihcc pubmed","probabilities":0.962963,"Title":"Clinicopathologic significance of Sox2, CD44 and CD44v6 expression in intrahepatic cholangiocarcinoma","Abstract":"Embryonic stem cells (ESC) and cancer stem cells (CSC) have a capacity for self-renewal and differentiation into multiple cell lineages. Sox2 plays a critical role in ESC and has been shown to participate in carcinogenesis and tumor progression in many human cancers. CD44 and CD44v6 are putative CSC markers and their association with tumor progression, metastasis, and tumor relapse after treatment has been demonstrated. We evaluated the immunoexpression of Sox2, CD44, and CD44v6 in 85 cases of Intrahepatic cholangiocarcinomas (IHCC) and assessed their prognostic significance. Sox2 expression showed a significant association with lymph node metastasis (p = 0.025), T4 stage (p = 0.046), and worse overall survival (p = 0.047). Greater expression of Sox2 was observed in IHCC with poor differentiation, vascular invasion, and stage IV, without statistical significance (p > 0.05). CD44 expression showed an association with periductal infiltrative type (p = 0.034), poor differentiation (p = 0.012), and vascular invasion (p = 0.009). CD44v6 expression was evident in patients with stage IV (p = 0.019). These results demonstrated that Sox2 expression is associated with aggressive behavior and poor overall survival in IHCC.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathologic significance of Sox2, CD44 and CD44v6 expression in intrahepatic cholangiocarcinoma Embryonic stem cells (ESC) and cancer stem cells (CSC) have a capacity for self-renewal and differentiation into multiple cell lineages. Sox2 plays a critical role in ESC and has been shown to participate in carcinogenesis and tumor progression in many human cancers. CD44 and CD44v6 are putative CSC markers and their association with tumor progression, metastasis, and tumor relapse after treatment has been demonstrated. We evaluated the immunoexpression of Sox2, CD44, and CD44v6 in 85 cases of Intrahepatic cholangiocarcinomas (IHCC) and assessed their prognostic significance. Sox2 expression showed a significant association with lymph node metastasis (p = 0.025), T4 stage (p = 0.046), and worse overall survival (p = 0.047). Greater expression of Sox2 was observed in IHCC with poor differentiation, vascular invasion, and stage IV, without statistical significance (p > 0.05). CD44 expression showed an association with periductal infiltrative type (p = 0.034), poor differentiation (p = 0.012), and vascular invasion (p = 0.009). CD44v6 expression was evident in patients with stage IV (p = 0.019). These results demonstrated that Sox2 expression is associated with aggressive behavior and poor overall survival in IHCC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"genetic polymorphism drug metabolizing enzymes association risk bile duct cancer cholangiocarcinoma cca common cancer endemic areas liver fluke infection although liver fluke recognized carcinogenic agent cholangiocarcinogenesis factors may play important roles bringing high prevalence cancer populations region drug metabolizing enzymes dme essential detoxification toxic carcinogenic chemicals moreover dme play alternative role activating chemicals toxic metabolites large variation dme activity among individuals partly due polymorphism genes encoding enzymes defective variant alleles dme genes may modify risk cancer exposeed carcinogenic agents focus review dme genes reported associated cca risk include cyp1a2 arylamine n acetyltransferase 1 nat1 nat2 nadph quinone oxidorecutase 1 nqo1 glutathione transferase m1 gstm1 gstt1 gsto1 methylenetetrahydrofolate reductase mthfr mutant alleles reportedly associated increased risk include cyp1a2 1f gstt1 null gsto1 mthfr 677c whereas slow nat2 nqo1 2 decrease risk nat1 variants gstm1 null effect genes modify risk cancer potentially interaction exposure certain environmental conditions thereby altering metabolism causative agents pubmed","probabilities":0.9799733,"Title":"Genetic polymorphism of drug metabolizing enzymes in association with risk of bile duct cancer","Abstract":"Cholangiocarcinoma (CCA) is the most common cancer in endemic areas of liver fluke infection. Although the liver fluke is recognized as a carcinogenic agent in cholangiocarcinogenesis, other factors may play important roles in bringing about the high prevalence of the cancer in populations of this region. Drug metabolizing enzymes (DME) are essential for detoxification of toxic and carcinogenic chemicals. Moreover, DME can play an alternative role by activating chemicals to more toxic metabolites. The large variation of DME activity among individuals is partly due to polymorphism of the genes encoding enzymes. Defective or variant alleles of DME genes may modify the risk of cancer in those who are exposeed to carcinogenic agents. The focus in this review is on DME genes which have been reported to be associated with CCA risk. These include CYP1A2, arylamine- N-acetyltransferase-1 (NAT1) and NAT2, NADPH-quinone oxidorecutase-1 (NQO1), glutathione-S-transferase M1 (GSTM1), GSTT1, GSTO1 and methylenetetrahydrofolate reductase (MTHFR). Mutant alleles which have been reportedly associated with an increased risk include CYP1A2*1F, GSTT1 null, GSTO1 and MTHFR 677C>T, whereas, slow NAT2 and NQO1*2 decrease risk and NAT1 variants and GSTM1 null have no effect. These genes modify the risk of cancer potentially by interaction and exposure with certain environmental conditions, thereby altering the metabolism of causative agents.","Source":"PubMed","category":"HUMAN","training_data":"Genetic polymorphism of drug metabolizing enzymes in association with risk of bile duct cancer Cholangiocarcinoma (CCA) is the most common cancer in endemic areas of liver fluke infection. Although the liver fluke is recognized as a carcinogenic agent in cholangiocarcinogenesis, other factors may play important roles in bringing about the high prevalence of the cancer in populations of this region. Drug metabolizing enzymes (DME) are essential for detoxification of toxic and carcinogenic chemicals. Moreover, DME can play an alternative role by activating chemicals to more toxic metabolites. The large variation of DME activity among individuals is partly due to polymorphism of the genes encoding enzymes. Defective or variant alleles of DME genes may modify the risk of cancer in those who are exposeed to carcinogenic agents. The focus in this review is on DME genes which have been reported to be associated with CCA risk. These include CYP1A2, arylamine- N-acetyltransferase-1 (NAT1) and NAT2, NADPH-quinone oxidorecutase-1 (NQO1), glutathione-S-transferase M1 (GSTM1), GSTT1, GSTO1 and methylenetetrahydrofolate reductase (MTHFR). Mutant alleles which have been reportedly associated with an increased risk include CYP1A2*1F, GSTT1 null, GSTO1 and MTHFR 677C>T, whereas, slow NAT2 and NQO1*2 decrease risk and NAT1 variants and GSTM1 null have no effect. These genes modify the risk of cancer potentially by interaction and exposure with certain environmental conditions, thereby altering the metabolism of causative agents. PubMed","prediction_labels":"HUMAN"},{"cleaned":"histopathologic type predicts survival patients ampullary carcinoma resection meta analysis objectives results studies prognostic value histopathologic differentiation intestinal pancreatobiliary types ampullary carcinoma resection conflicting meta analysis undertaken investigate issue methods systematic literature search performed identify articles published january 2000 august 2016 data pooled meta analysis using review manager 5 3 results twenty three retrospective studies involving total 2234 patients identified inclusion 1021 45 7 intestinal type tumors 899 40 2 pancreaticobiliary type tumors patients pancreaticobiliary type high rates poor tumor differentiation p 0 001 lymph node metastasis p 0 001 vascular invasion p 0 001 perineural invasion p 0 001 positive resection margins p 0 004 compared intestinal type pancreaticobiliary type predicted worse overall survival hazard ratio hr 1 84 95 ci 1 49 2 27 p 0 001 disease free survival hr 1 93 95 ci 1 23 3 01 p 0 004 conclusion histopathologic type major impact survival patients ampullary carcinoma resection pancreaticobiliary type reflects aggressive tumor biology associated worse survival pubmed","probabilities":0.9799733,"Title":"The histopathologic type predicts survival of patients with ampullary carcinoma after resection: A meta-analysis","Abstract":"OBJECTIVES: The results of studies on the prognostic value of histopathologic differentiation of the intestinal and pancreatobiliary types of ampullary carcinoma after resection are conflicting. A meta-analysis was undertaken to investigate this issue. METHODS: A systematic literature search was performed to identify articles published from January 2000 to August 2016. Data were pooled for meta-analysis using Review Manager 5.3. RESULTS: Twenty three retrospective studies involving a total of 2234 patients were identified for inclusion, of whom 1021 (45.7%) had intestinal type tumors and 899 (40.2%) had pancreaticobiliary type tumors. Patients with the pancreaticobiliary type had high rates of poor tumor differentiation (P < 0.001), lymph node metastasis (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and positive resection margins (P = 0.004), as compared with those with the intestinal type. The pancreaticobiliary type predicted a worse overall survival (hazard ratio [HR] 1.84, 95% CI 1.49-2.27; P < 0.001) and disease-free survival (HR 1.93, 95% CI 1.23-3.01; P = 0.004). CONCLUSION: The histopathologic type has major impact on survival in patients with ampullary carcinoma after resection, and the pancreaticobiliary type reflects a more aggressive tumor biology and is associated with worse survival.","Source":"PubMed","category":"HUMAN","training_data":"The histopathologic type predicts survival of patients with ampullary carcinoma after resection: A meta-analysis OBJECTIVES: The results of studies on the prognostic value of histopathologic differentiation of the intestinal and pancreatobiliary types of ampullary carcinoma after resection are conflicting. A meta-analysis was undertaken to investigate this issue. METHODS: A systematic literature search was performed to identify articles published from January 2000 to August 2016. Data were pooled for meta-analysis using Review Manager 5.3. RESULTS: Twenty three retrospective studies involving a total of 2234 patients were identified for inclusion, of whom 1021 (45.7%) had intestinal type tumors and 899 (40.2%) had pancreaticobiliary type tumors. Patients with the pancreaticobiliary type had high rates of poor tumor differentiation (P < 0.001), lymph node metastasis (P < 0.001), vascular invasion (P < 0.001), perineural invasion (P < 0.001), and positive resection margins (P = 0.004), as compared with those with the intestinal type. The pancreaticobiliary type predicted a worse overall survival (hazard ratio [HR] 1.84, 95% CI 1.49-2.27; P < 0.001) and disease-free survival (HR 1.93, 95% CI 1.23-3.01; P = 0.004). CONCLUSION: The histopathologic type has major impact on survival in patients with ampullary carcinoma after resection, and the pancreaticobiliary type reflects a more aggressive tumor biology and is associated with worse survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"primary sclerosing cholangitis premalignant biliary tract disease surveillance management primary sclerosing cholangitis psc premalignant biliary tract disease confers significant risk development cholangiocarcinoma cca chronic biliary tract inflammation psc promotes pro oncogenic processes cellular proliferation induction dna damage alterations extracellular matrix cholestasis diagnosis malignancy psc challenging inflammation related changes psc may produce dominant biliary tract strictures mimicking cca biomarkers detection methylated genes biliary specimens represent noninvasive techniques may discriminate malignant biliary ductal changes psc strictures however conventional cytology advanced cytologic techniques fluorescence situ hybridization polysomy remain practice standard diagnosing cca psc curative treatment options malignancy arising psc limited subset patients selected using stringent criteria liver transplantation neoadjuvant chemoradiation potential curative therapy however patients advanced malignancy time diagnosis advances directed identifying high risk patients early cancer detection development chemopreventive strategies essential better manage cancer risk premalignant disease better understanding dysplasia definition especially natural history also needed disease herein review recent developments understanding risk factors pathogenic mechanisms psc associated cca well advances early detection therapies pubmed","probabilities":0.9799733,"Title":"Primary Sclerosing Cholangitis as a Premalignant Biliary Tract Disease: Surveillance and Management","Abstract":"Primary sclerosing cholangitis (PSC) is a premalignant biliary tract disease that confers a significant risk for the development of cholangiocarcinoma (CCA). The chronic biliary tract inflammation of PSC promotes pro-oncogenic processes such as cellular proliferation, induction of DNA damage, alterations of the extracellular matrix, and cholestasis. The diagnosis of malignancy in PSC can be challenging because inflammation-related changes in PSC may produce dominant biliary tract strictures mimicking CCA. Biomarkers such as detection of methylated genes in biliary specimens represent noninvasive techniques that may discriminate malignant biliary ductal changes from PSC strictures. However, conventional cytology and advanced cytologic techniques such as fluorescence in situ hybridization for polysomy remain the practice standard for diagnosing CCA in PSC. Curative treatment options of malignancy arising in PSC are limited. For a subset of patients selected by using stringent criteria, liver transplantation after neoadjuvant chemoradiation is a potential curative therapy. However, most patients have advanced malignancy at the time of diagnosis. Advances directed at identifying high-risk patients, early cancer detection, and development of chemopreventive strategies will be essential to better manage the cancer risk in this premalignant disease. A better understanding of dysplasia definition and especially its natural history is also needed in this disease. Herein, we review recent developments in our understanding of the risk factors, pathogenic mechanisms of PSC associated with CCA, as well as advances in early detection and therapies.","Source":"PubMed","category":"HUMAN","training_data":"Primary Sclerosing Cholangitis as a Premalignant Biliary Tract Disease: Surveillance and Management Primary sclerosing cholangitis (PSC) is a premalignant biliary tract disease that confers a significant risk for the development of cholangiocarcinoma (CCA). The chronic biliary tract inflammation of PSC promotes pro-oncogenic processes such as cellular proliferation, induction of DNA damage, alterations of the extracellular matrix, and cholestasis. The diagnosis of malignancy in PSC can be challenging because inflammation-related changes in PSC may produce dominant biliary tract strictures mimicking CCA. Biomarkers such as detection of methylated genes in biliary specimens represent noninvasive techniques that may discriminate malignant biliary ductal changes from PSC strictures. However, conventional cytology and advanced cytologic techniques such as fluorescence in situ hybridization for polysomy remain the practice standard for diagnosing CCA in PSC. Curative treatment options of malignancy arising in PSC are limited. For a subset of patients selected by using stringent criteria, liver transplantation after neoadjuvant chemoradiation is a potential curative therapy. However, most patients have advanced malignancy at the time of diagnosis. Advances directed at identifying high-risk patients, early cancer detection, and development of chemopreventive strategies will be essential to better manage the cancer risk in this premalignant disease. A better understanding of dysplasia definition and especially its natural history is also needed in this disease. Herein, we review recent developments in our understanding of the risk factors, pathogenic mechanisms of PSC associated with CCA, as well as advances in early detection and therapies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"high expression protein tyrosine kinase 7 significantly associates invasiveness poor prognosis intrahepatic cholangiocarcinoma background incidence prevalence mortality intrahepatic cholangiocarcinoma icc increasing worldwide protein tyrosine kinase 7 ptk7 upregulated many common human cancers however expression icc studied present study aimed explore underlying mechanism ptk7 icc materials methods role ptk7 studied vitro suppressing ptk7 expression icc cell lines vivo effect ptk7 evaluated using nude mouse model inoculated human icc cell line also examined role ptk7 human icc samples results cells high ptk7 expression exhibited higher proliferation dna synthesis invasion migration abilities cells low ptk7 expression knockdown ptk7 small interfering rna sirna high ptk7 expressing cells resulted impairment invasion migration dna synthesis regulation several cell cycle related proteins also induced cell apoptosis decreased phospho rhoa expression xenograft nude mouse model ptk7 sirna resulted reduction tumor size compared scrambled sirna injection ptk7 expression higher human icc normal bile duct patients low expression ptk7 longer disease free survival overall survival high expression conclusions ptk7 expression plays important role invasiveness icc cells leads poor prognosis icc patients thus ptk7 used prognostic indicator inhibition ptk7 expression new therapeutic target icc google scholar","probabilities":0.9467213,"Title":"High Expression Of Protein Tyrosine Kinase 7 Significantly Associates With Invasiveness And Poor Prognosis In Intrahepatic Cholangiocarcinoma","Abstract":"Background\nThe incidence, prevalence, and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. Protein tyrosine kinase-7 (PTK7) is upregulated in many common human cancers. However, its expression in ICC has not been studied. The present study aimed to explore the underlying mechanism of PTK7 in ICC.\nMaterials and Methods\nThe role of PTK7 was studied in vitro by suppressing PTK7 expression in ICC cell lines. The in vivo effect of PTK7 was evaluated using a nude mouse model inoculated with a human ICC cell line. We also examined the role of PTK7 in human ICC samples.\nResults\nCells with high PTK7 expression exhibited higher proliferation, DNA synthesis, invasion, and migration abilities than did cells with low PTK7 expression. The knockdown of PTK7 with small interfering RNA (siRNA) in high PTK7 expressing cells resulted in impairment of invasion, migration, and DNA synthesis through the regulation of several cell-cycle-related proteins. It also induced cell apoptosis and decreased phospho-RhoA expression. In a xenograft nude mouse model, PTK7 siRNA resulted in a reduction of the tumor size, compared with scrambled siRNA injection. PTK7 expression was higher in human ICC than in the normal bile duct. Patients with low expression of PTK7 had a longer disease-free survival and overall survival than those with high expression.\nConclusions\nPTK7 expression plays an important role in the invasiveness of ICC cells and leads to a poor prognosis in ICC patients. Thus, PTK7 can be used as a prognostic indicator, and the inhibition of PTK7 expression could be a new therapeutic target for ICC.","Source":"Google Scholar","category":"ANIMAL","training_data":"High Expression Of Protein Tyrosine Kinase 7 Significantly Associates With Invasiveness And Poor Prognosis In Intrahepatic Cholangiocarcinoma Background\nThe incidence, prevalence, and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing worldwide. Protein tyrosine kinase-7 (PTK7) is upregulated in many common human cancers. However, its expression in ICC has not been studied. The present study aimed to explore the underlying mechanism of PTK7 in ICC.\nMaterials and Methods\nThe role of PTK7 was studied in vitro by suppressing PTK7 expression in ICC cell lines. The in vivo effect of PTK7 was evaluated using a nude mouse model inoculated with a human ICC cell line. We also examined the role of PTK7 in human ICC samples.\nResults\nCells with high PTK7 expression exhibited higher proliferation, DNA synthesis, invasion, and migration abilities than did cells with low PTK7 expression. The knockdown of PTK7 with small interfering RNA (siRNA) in high PTK7 expressing cells resulted in impairment of invasion, migration, and DNA synthesis through the regulation of several cell-cycle-related proteins. It also induced cell apoptosis and decreased phospho-RhoA expression. In a xenograft nude mouse model, PTK7 siRNA resulted in a reduction of the tumor size, compared with scrambled siRNA injection. PTK7 expression was higher in human ICC than in the normal bile duct. Patients with low expression of PTK7 had a longer disease-free survival and overall survival than those with high expression.\nConclusions\nPTK7 expression plays an important role in the invasiveness of ICC cells and leads to a poor prognosis in ICC patients. Thus, PTK7 can be used as a prognostic indicator, and the inhibition of PTK7 expression could be a new therapeutic target for ICC. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"polo like kinase 3 associated improved overall survival cholangiocarcinoma background aims cholangiocarcinomas cca paradoxically express death ligand trail thus dependent effective survival signals circumvent apoptosis hedgehog signalling exerts major survival signals cca regulating serine threonine kinase polo like kinase plk 2 aimed examine role plk1 2 3 expression cca tumour biology methods employed cca samples 73 patients human hucct 1 mz cha1 kmch 1 cca cells immunohistochemistry plk1 2 3 performed using tissue microarrays representative tumour areas results plk1 2 3 immunoreactive cancer cells present cca samples however plk1 especially plk3 expressed higher amounts within cca cells compared normal liver given fibroblast growth factor fgf induce plk3 expression also present cca examined effect fgf plk3 vitro indeed rhfgf rapidly increased plk3 mrna expression three cca cell lines giving explanation abundant plk3 presence tissue samples clinicopathologically plk3 expression associated decreased tumour cell migration lymph blood vessel infiltration whereas higher levels plk1 correlated larger tumour sizes moreover strong plk3 expression associated prolonged overall survival conclusions results suggest plk3 predominantly expressed cca cells high plk3 expression correlates prolonged overall survival observations might implications prognosis prediction human cca well potential therapeutic use polo like kinase inhibitors e plk1 2 specifity stn","probabilities":0.9467213,"Title":"Polo-Like Kinase 3 Is Associated With Improved Overall Survival In Cholangiocarcinoma","Abstract":"Background & aims: Cholangiocarcinomas (CCA) paradoxically express the death ligand TRAIL and thus, are dependent on effective survival signals to circumvent apoptosis. Hedgehog signalling exerts major survival signals in CCA by regulating serine/threonine kinase polo-like kinase (PLK)2. We here aimed to examine the role of PLK1/2/3 expression for CCA tumour biology. \r\n\r\n Methods: We employed CCA samples from 73 patients and human HUCCT-1/Mz-CHA1/KMCH-1 CCA cells. Immunohistochemistry for PLK1/2/3 was performed using tissue microarrays from representative tumour areas. \r\n\r\n Results: PLK1/2/3-immunoreactive cancer cells were present in most of the CCA samples. However, only PLK1 and especially PLK3 were expressed in higher amounts within CCA cells as compared to normal liver. Given that fibroblast growth factor (FGF) can induce PLK3 expression and also is present in CCA, we examined the effect of FGF on PLK3 in vitro. Indeed, rhFGF rapidly increased PLK3 mRNA expression all three CCA cell lines giving an explanation for the abundant PLK3 presence in the tissue samples. Clinicopathologically, PLK3 expression was associated with decreased tumour cell migration and lymph/blood vessel infiltration whereas higher levels of PLK1 were correlated with larger tumour sizes. Moreover, strong PLK3 expression was associated with prolonged overall survival. \r\n\r\n Conclusions: The results suggest that PLK3 predominantly is expressed in CCA cells and that high PLK3 expression correlates with prolonged overall survival. These observations might have implications for prognosis prediction of human CCA as well as the potential therapeutic use of polo-like kinase inhibitors (i.e., PLK1/2 specifity).","Source":"STN","category":"ANIMAL","training_data":"Polo-Like Kinase 3 Is Associated With Improved Overall Survival In Cholangiocarcinoma Background & aims: Cholangiocarcinomas (CCA) paradoxically express the death ligand TRAIL and thus, are dependent on effective survival signals to circumvent apoptosis. Hedgehog signalling exerts major survival signals in CCA by regulating serine/threonine kinase polo-like kinase (PLK)2. We here aimed to examine the role of PLK1/2/3 expression for CCA tumour biology. \r\n\r\n Methods: We employed CCA samples from 73 patients and human HUCCT-1/Mz-CHA1/KMCH-1 CCA cells. Immunohistochemistry for PLK1/2/3 was performed using tissue microarrays from representative tumour areas. \r\n\r\n Results: PLK1/2/3-immunoreactive cancer cells were present in most of the CCA samples. However, only PLK1 and especially PLK3 were expressed in higher amounts within CCA cells as compared to normal liver. Given that fibroblast growth factor (FGF) can induce PLK3 expression and also is present in CCA, we examined the effect of FGF on PLK3 in vitro. Indeed, rhFGF rapidly increased PLK3 mRNA expression all three CCA cell lines giving an explanation for the abundant PLK3 presence in the tissue samples. Clinicopathologically, PLK3 expression was associated with decreased tumour cell migration and lymph/blood vessel infiltration whereas higher levels of PLK1 were correlated with larger tumour sizes. Moreover, strong PLK3 expression was associated with prolonged overall survival. \r\n\r\n Conclusions: The results suggest that PLK3 predominantly is expressed in CCA cells and that high PLK3 expression correlates with prolonged overall survival. These observations might have implications for prognosis prediction of human CCA as well as the potential therapeutic use of polo-like kinase inhibitors (i.e., PLK1/2 specifity). STN","prediction_labels":"ANIMAL"},{"cleaned":"enhancement patterns intrahepatic cholangiocarcinoma contrast enhanced ultrasound correlation clinicopathologic findings prognosis evaluate correlations enhancement pattern intrahepatic cholangiocarcinoma icc contrast enhanced ultrasound ceus clinicopathologic findings prognosis retrospective study performed 197 patients mass forming icc underwent pre operative ceus surgical resection contrast medium employed ceus sonovue contains microbubbles consisting sulfur hexafluoride bubbles within phospholipid shell study approved institutional review board informed consent waived patients classified arterial rim like enhancement group arterial non rim like enhancement group arterial enhancement patterns correlated clinicopathologic factors overall survival os times calculated using kaplan meier method differences groups compared log rank test univariate multivariate cox regression models os used evaluate independent prognostic factors mean range icc tumor size arterial rim like group 59 41 22 09 mm 20 100 mm similar arterial non rim like group 59 82 30 35 mm 14 162 mm p 0 914 arterial enhancement patterns correlated chronic viral hepatitis cirrhosis vascular invasion lymph node metastasis single multiple tumors total 78 patients 39 6 exhibited arterial rim like enhancement 119 patients 60 4 exhibited arterial non rim like enhancement arterial enhancement pattern p 0 045 vascular invasion p 0 005 lymph node metastasis p 0 000 number tumors p 0 001 independent prognostic factors os arterial non rim like enhancement pattern icc ceus independent prognostic factor better os may offer new information predicting prognosis icc patients surgical resection pubmed","probabilities":0.9799733,"Title":"Enhancement Patterns of Intrahepatic Cholangiocarcinoma on Contrast-Enhanced Ultrasound: Correlation with Clinicopathologic Findings and Prognosis","Abstract":"To evaluate the correlations between the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and clinicopathologic findings and prognosis, a retrospective study was performed on 197 patients with mass-forming ICC who underwent pre-operative CEUS and surgical resection. The contrast medium we employed in CEUS was SonoVue, which contains microbubbles consisting of sulfur hexafluoride bubbles within a phospholipid shell. This study was approved by the institutional review board with informed consent waived. Patients were classified into an arterial rim-like enhancement group or an arterial non-rim-like enhancement group, and arterial enhancement patterns were correlated with clinicopathologic factors. Overall survival (OS) times were calculated using the Kaplan-Meier method, and differences between groups were compared with the log-rank test. Univariate and multivariate Cox regression models for OS were used to evaluate the independent prognostic factors. The mean and range of ICC tumor size of the arterial rim-like group (59.41 ± 22.09 mm, 20-100 mm) were similar to those of the arterial non-rim-like group (59.82 ± 30.35 mm, 14-162 mm, p = 0.914). Arterial enhancement patterns were correlated with chronic viral hepatitis or cirrhosis, vascular invasion, lymph node metastasis and single/multiple tumors. A total of 78 patients (39.6%) exhibited arterial rim-like enhancement, and the other 119 patients (60.4%) exhibited arterial non-rim-like enhancement. Arterial enhancement pattern (p = 0.045), vascular invasion (p = 0.005), lymph node metastasis (p = 0.000) and number of tumors (p = 0.001) were independent prognostic factors for OS. The arterial non-rim-like enhancement pattern of ICC on CEUS is an independent prognostic factor for better OS and may offer new information for predicting the prognosis of ICC patients before surgical resection.","Source":"PubMed","category":"HUMAN","training_data":"Enhancement Patterns of Intrahepatic Cholangiocarcinoma on Contrast-Enhanced Ultrasound: Correlation with Clinicopathologic Findings and Prognosis To evaluate the correlations between the enhancement pattern of intrahepatic cholangiocarcinoma (ICC) on contrast-enhanced ultrasound (CEUS) and clinicopathologic findings and prognosis, a retrospective study was performed on 197 patients with mass-forming ICC who underwent pre-operative CEUS and surgical resection. The contrast medium we employed in CEUS was SonoVue, which contains microbubbles consisting of sulfur hexafluoride bubbles within a phospholipid shell. This study was approved by the institutional review board with informed consent waived. Patients were classified into an arterial rim-like enhancement group or an arterial non-rim-like enhancement group, and arterial enhancement patterns were correlated with clinicopathologic factors. Overall survival (OS) times were calculated using the Kaplan-Meier method, and differences between groups were compared with the log-rank test. Univariate and multivariate Cox regression models for OS were used to evaluate the independent prognostic factors. The mean and range of ICC tumor size of the arterial rim-like group (59.41 ± 22.09 mm, 20-100 mm) were similar to those of the arterial non-rim-like group (59.82 ± 30.35 mm, 14-162 mm, p = 0.914). Arterial enhancement patterns were correlated with chronic viral hepatitis or cirrhosis, vascular invasion, lymph node metastasis and single/multiple tumors. A total of 78 patients (39.6%) exhibited arterial rim-like enhancement, and the other 119 patients (60.4%) exhibited arterial non-rim-like enhancement. Arterial enhancement pattern (p = 0.045), vascular invasion (p = 0.005), lymph node metastasis (p = 0.000) and number of tumors (p = 0.001) were independent prognostic factors for OS. The arterial non-rim-like enhancement pattern of ICC on CEUS is an independent prognostic factor for better OS and may offer new information for predicting the prognosis of ICC patients before surgical resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"model predict survival surgical resection intrahepatic cholangiocarcinoma mayo clinic experience background 7th edition american joint committee cancer ajcc staging system recently validated shown predict survival patients intrahepatic cholangiocarcinoma icc present study attempted investigate validity findings methods single centre retrospective cohort study conducted histopathological restaging disease subsequent primary surgical resection carried consecutive icc patients overall survival compared using kaplan meier estimates log rank tests results total 150 patients underwent surgery 126 84 met present study inclusion criteria 126 patients 68 54 female median length follow 4 5 years median patient age 58 years range 24 79 years median body mass index 27 kg m 2 range 17 46 kg m 2 staging according ajcc 7th edition categorized 33 26 patients stage disease 27 21 stage ii disease five 4 stage iii disease 61 48 stage iva disease ajcc 7th edition failed accurately stratify survival current cohort analysis revealed significantly worse survival microvascular invasion tumour size 5 cm grade 4 disease multiple tumours positive lymph nodes p 0 001 negative resection margin associated improved survival p 0 001 conclusions ajcc 7th edition accurately predict survival patients icc multivariable model including tumour size differentiation addition criteria used ajcc 7th edition may offer accurate method predicting survival patients icc pubmed","probabilities":0.9799733,"Title":"Model to predict survival after surgical resection of intrahepatic cholangiocarcinoma: the Mayo Clinic experience","Abstract":"BACKGROUND: The 7th edition of the American Joint Committee on Cancer (AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma (ICC). The present study attempted to investigate the validity of these findings. METHODS: A single-centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan-Meier estimates and log-rank tests. RESULTS: A total of 150 patients underwent surgery, 126 (84%) of whom met the present study's inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow-up was 4.5 years. The median patient age was 58 years (range: 24-79 years). Median body mass index was 27 kg/m(2) (range: 17-46 kg/m(2) ). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes (P < 0.001). A negative resection margin was associated with improved survival (P < 0.001). CONCLUSIONS: The AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC.","Source":"PubMed","category":"HUMAN","training_data":"Model to predict survival after surgical resection of intrahepatic cholangiocarcinoma: the Mayo Clinic experience BACKGROUND: The 7th edition of the American Joint Committee on Cancer (AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma (ICC). The present study attempted to investigate the validity of these findings. METHODS: A single-centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan-Meier estimates and log-rank tests. RESULTS: A total of 150 patients underwent surgery, 126 (84%) of whom met the present study's inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow-up was 4.5 years. The median patient age was 58 years (range: 24-79 years). Median body mass index was 27 kg/m(2) (range: 17-46 kg/m(2) ). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes (P < 0.001). A negative resection margin was associated with improved survival (P < 0.001). CONCLUSIONS: The AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison cancer incidence china usa objective incidence cancer varies around globe especially less developed developed regions aim study explore differences cancer incidence china usa methods data obtained globocan 2008 database estimated numbers new cancer cases usa obtained american cancer society numbers cases china including urban rural areas obtained 36 cancer registries 2003 2005 cancer incidence major sites china usa analyzed results china lung cancer predominant type cancer detected males females breast cancer main type cancer gastrointestinal cancers liver stomach esophagus commonly seen china usa significant difference incidence melanoma skin observed china usa comparison differences age standardized rates world population asrws major cancer sites two countries 4 sites males e nasopharynx esophagus stomach liver 6 sites females e nasopharynx esophagus stomach liver gallbladder cervix uteri showed higher cancer incidence rates china usa conclusions significant differences cancer incidence sites found two countries cancer may prevented public education awareness programs promote cancer prevention china especially lung breast gastrointestinal region must also implemented google scholar","probabilities":0.9799733,"Title":"Comparison Of Cancer Incidence Between China And The Usa","Abstract":"Objective\nThe incidence of cancer varies around the globe, especially between less-developed and developed regions. The aim of this study is to explore differences in cancer incidence between China and the USA.\nMethods\nData were obtained from the GLOBOCAN 2008 database. Estimated numbers of new cancer cases in the USA were obtained from the American Cancer Society, while the numbers of cases in China, including those in urban and rural areas, were obtained from 36 cancer registries (2003-2005). Cancer incidence for major sites between China and the USA were analyzed.\nResults\nIn China, lung cancer was the predominant type of cancer detected in males; in females, breast cancer was the main type of cancer. Gastrointestinal cancers, such as those of the liver, stomach, and esophagus, were more commonly seen in China than in the USA. A significant difference in the incidence of melanoma of the skin was observed between China and the USA. During comparison of differences in the age-standardized rates by world population (ASRWs) of major cancer sites between the two countries, 4 sites in males (i.e., nasopharynx, esophagus, stomach, and liver) and 6 sites in females (i.e., nasopharynx, esophagus, stomach, liver, gallbladder, and cervix uteri) showed higher cancer incidence rates in China than in the USA.\nConclusions\nSignificant differences in cancer incidence sites were found between the two countries. Cancer may be prevented through public education and awareness. Programs to promote cancer prevention in China, especially those of the lung, breast, and gastrointestinal region, must also be implemented.","Source":"Google Scholar","category":"HUMAN","training_data":"Comparison Of Cancer Incidence Between China And The Usa Objective\nThe incidence of cancer varies around the globe, especially between less-developed and developed regions. The aim of this study is to explore differences in cancer incidence between China and the USA.\nMethods\nData were obtained from the GLOBOCAN 2008 database. Estimated numbers of new cancer cases in the USA were obtained from the American Cancer Society, while the numbers of cases in China, including those in urban and rural areas, were obtained from 36 cancer registries (2003-2005). Cancer incidence for major sites between China and the USA were analyzed.\nResults\nIn China, lung cancer was the predominant type of cancer detected in males; in females, breast cancer was the main type of cancer. Gastrointestinal cancers, such as those of the liver, stomach, and esophagus, were more commonly seen in China than in the USA. A significant difference in the incidence of melanoma of the skin was observed between China and the USA. During comparison of differences in the age-standardized rates by world population (ASRWs) of major cancer sites between the two countries, 4 sites in males (i.e., nasopharynx, esophagus, stomach, and liver) and 6 sites in females (i.e., nasopharynx, esophagus, stomach, liver, gallbladder, and cervix uteri) showed higher cancer incidence rates in China than in the USA.\nConclusions\nSignificant differences in cancer incidence sites were found between the two countries. Cancer may be prevented through public education and awareness. Programs to promote cancer prevention in China, especially those of the lung, breast, and gastrointestinal region, must also be implemented. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cpg island methylation study liver fluke related cholangiocarcinoma background genetic changes widely reported association cholangiocarcinoma cca epigenetic changes poorly characterised aimed evaluate cpg island hypermethylation cca candidate loci may potential diagnostic prognostic biomarkers methods analysed methylation 26 cpg islands 102 liver fluke related cca 29 adjacent normal samples using methylation specific pcr msp methylation interest loci confirmed using pyrosequencing combined bisulfite restriction analysis protein expression immunohistochemistry results number cpg islands opcml sfrp1 hic1 pten dcr1 showed frequency hypermethylation 28 cca adjacent normal tissues results showed 91 cca methylated least one cpg island opcml frequently methylated locus 72 5 frequently methylated less differentiated cca patients methylated dcr1 significantly longer overall survival median 41 7 vs 21 7 weeks p 0 027 low protein expression found 70 cca methylation opcml dcr1 conclusion aberrant hypermethylation certain loci common event liver fluke related cca may potentially contribute cholangiocarcinogenesis opcml dcr1 might serve methylation biomarkers cca readily examined msp pubmed","probabilities":0.9285714,"Title":"CpG-island methylation study of liver fluke-related cholangiocarcinoma","Abstract":"BACKGROUND: Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers. METHODS: We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry. RESULTS: A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1. CONCLUSION: Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP.","Source":"PubMed","category":"ANIMAL","training_data":"CpG-island methylation study of liver fluke-related cholangiocarcinoma BACKGROUND: Genetic changes have been widely reported in association with cholangiocarcinoma (CCA), while epigenetic changes are poorly characterised. We aimed to further evaluate CpG-island hypermethylation in CCA at candidate loci, which may have potential as diagnostic or prognostic biomarkers. METHODS: We analysed methylation of 26 CpG-islands in 102 liver fluke related-CCA and 29 adjacent normal samples using methylation-specific PCR (MSP). Methylation of interest loci was confirmed using pyrosequencing and/or combined bisulfite restriction analysis, and protein expression by immunohistochemistry. RESULTS: A number of CpG-islands (OPCML, SFRP1, HIC1, PTEN and DcR1) showed frequency of hypermethylation in >28% of CCA, but not adjacent normal tissues. The results showed that 91% of CCA were methylated in at least one CpG-island. The OPCML was the most frequently methylated locus (72.5%) and was more frequently methylated in less differentiated CCA. Patients with methylated DcR1 had significantly longer overall survival (Median; 41.7 vs 21.7 weeks, P=0.027). Low-protein expression was found in >70% of CCA with methylation of OPCML or DcR1. CONCLUSION: Aberrant hypermethylation of certain loci is a common event in liver fluke-related CCA and may potentially contribute to cholangiocarcinogenesis. The OPCML and DcR1 might serve as methylation biomarkers in CCA that can be readily examined by MSP. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"body mass index cancer incidence finrisk study relation body mass index bmi risk cancer incidence controversial cancer incidence 1972 2008 relation bmi investigated prospective cohort 54 725 finns aged 24 74 years free cancer enrollment mean follow 20 6 years 8 429 15 4 incident cancers recorded 4 208 49 9 men parametric nonparametric approaches used evaluate shape relationship bmi incidence cancer bmi linear positive association incidence cancers colon liver kidney bladder sites combined men cancers stomach colon gallbladder ovary women inverse association incidence cancers lung men lung breast women j shaped association incidence cancers combined women high bmi women associated increased overall cancer risk never smokers reduced risk smokers elevated bmi associated increased risk incidence cancers certain sites pubmed","probabilities":0.9799733,"Title":"Body mass index and cancer incidence: the FINRISK study","Abstract":"The relation between body mass index (BMI) and risk of cancer incidence is controversial. Cancer incidence during 1972-2008 in relation to BMI was investigated in a prospective cohort of 54,725 Finns aged 24-74 years and free of cancer at enrollment. Over a mean follow-up of 20.6 years, 8,429 (15.4%) incident cancers were recorded, 4,208 (49.9%) from men. Both parametric and nonparametric approaches were used to evaluate the shape of the relationship between BMI and incidence of cancer. BMI had a linear positive association with incidence of cancers of the colon, liver, kidney, bladder and all sites combined in men, and of cancers of the stomach, colon, gallbladder and ovary in women, an inverse association with incidence of cancers of the lung in men and the lung and breast in women, a J-shaped association with incidence of all cancers combined in women. High BMI in women was associated with an increased overall cancer risk in never smokers but a reduced risk in smokers. Elevated BMI was associated with an increased risk of incidence of cancers of certain sites.","Source":"PubMed","category":"HUMAN","training_data":"Body mass index and cancer incidence: the FINRISK study The relation between body mass index (BMI) and risk of cancer incidence is controversial. Cancer incidence during 1972-2008 in relation to BMI was investigated in a prospective cohort of 54,725 Finns aged 24-74 years and free of cancer at enrollment. Over a mean follow-up of 20.6 years, 8,429 (15.4%) incident cancers were recorded, 4,208 (49.9%) from men. Both parametric and nonparametric approaches were used to evaluate the shape of the relationship between BMI and incidence of cancer. BMI had a linear positive association with incidence of cancers of the colon, liver, kidney, bladder and all sites combined in men, and of cancers of the stomach, colon, gallbladder and ovary in women, an inverse association with incidence of cancers of the lung in men and the lung and breast in women, a J-shaped association with incidence of all cancers combined in women. High BMI in women was associated with an increased overall cancer risk in never smokers but a reduced risk in smokers. Elevated BMI was associated with an increased risk of incidence of cancers of certain sites. PubMed","prediction_labels":"HUMAN"},{"cleaned":"body fatness cause cancer epidemiologic clues biologic mechanisms carrying excess body fat leading cause cancer epidemiologic evidence gives strong clues mechanisms link excess adiposity risk several cancer sites postmenopausal breast cancer endometrial cancer hyper estrogenic state induced excess body fatness likely cause esophageal cancer gallbladder cancer chronic local inflammation induced acid reflux gallstones likely cause liver cancer local inflammation induced hepatic fatty infiltration likely cause however several cancers known associated excess adiposity including cancers colon pancreas ovary kidney prostate specific causes known possible candidates include elevated systemic local tissue inflammation induced adiposity effects elevated levels leptin insulin igfs depressed immune function seen excess adiposity growing evidence intentional weight loss reduces circulating levels cancer associated factors also reduces cancer incidence recurrence better research needed understand mechanisms link excess body fat cancer risk well understand amount weight loss needed substantial cancer risk reduction finally develop better understanding mediators effects excess body fatness cancer risk identify pharmacologic interventions target mediators used complement weight loss order reduce cancer risk pubmed","probabilities":0.7966102,"Title":"Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms","Abstract":"Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cause. For esophageal cancer and gallbladder cancer, chronic local inflammation induced by acid reflux and gallstones is the likely cause, and for liver cancer, local inflammation induced by hepatic fatty infiltration is the likely cause. However, for several other cancers known to be associated with excess adiposity, including cancers of the colon, pancreas, ovary, kidney, and prostate, specific causes are not known. Possible candidates include elevated systemic or local tissue inflammation induced by adiposity and effects of the elevated levels of leptin, insulin, IGFs, and depressed immune function that are seen with excess adiposity. There is growing evidence that intentional weight loss not only reduces circulating levels of cancer-associated factors but that it also reduces cancer incidence and recurrence. Better research is needed to understand the mechanisms that link excess body fat to cancer risk as well as to understand the amount of weight loss needed for substantial cancer risk reduction. Finally, as we develop better understanding of the mediators of the effects of excess body fatness on cancer risk, we should identify pharmacologic interventions that target those mediators so that they can be used to complement weight loss in order to reduce cancer risk.","Source":"PubMed","category":"HUMAN","training_data":"Body fatness as a cause of cancer: epidemiologic clues to biologic mechanisms Carrying excess body fat is a leading cause of cancer. Epidemiologic evidence gives strong clues about the mechanisms that link excess adiposity to risk for several cancer sites. For postmenopausal breast cancer and endometrial cancer, the hyper-estrogenic state that is induced by excess body fatness is the likely cause. For esophageal cancer and gallbladder cancer, chronic local inflammation induced by acid reflux and gallstones is the likely cause, and for liver cancer, local inflammation induced by hepatic fatty infiltration is the likely cause. However, for several other cancers known to be associated with excess adiposity, including cancers of the colon, pancreas, ovary, kidney, and prostate, specific causes are not known. Possible candidates include elevated systemic or local tissue inflammation induced by adiposity and effects of the elevated levels of leptin, insulin, IGFs, and depressed immune function that are seen with excess adiposity. There is growing evidence that intentional weight loss not only reduces circulating levels of cancer-associated factors but that it also reduces cancer incidence and recurrence. Better research is needed to understand the mechanisms that link excess body fat to cancer risk as well as to understand the amount of weight loss needed for substantial cancer risk reduction. Finally, as we develop better understanding of the mediators of the effects of excess body fatness on cancer risk, we should identify pharmacologic interventions that target those mediators so that they can be used to complement weight loss in order to reduce cancer risk. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic delineation papillary cholangiocarcinoma based invasive proportion single institution study 184 patients background intraductal papillary neoplasm bile duct ipnb presumed precursor lesion biliary carcinogenesis clinicopathologically overlapping papillary cholangiocarcinomas pcc however ipnb standardized definition relationship remains equivocal herein aimed develop new prognostic model pcc focusing invasive proportion methods among 644 patients resected cholangiocarcinoma 1998 2011 184 28 intraductal exophytic papillary lesions divided 4 subsets based invasive component noninvasive pcc 1 n 14 10 pcc 2 n 32 11 50 pcc 3 n 60 50 pcc 4 n 78 remaining 460 identified non pccs npcc results invasion beyond duct wall regional lymph node metastases frequent npcc pcc p 001 five year survival better pcc 55 npcc 35 p 001 indicating papillary component significant independent prognosticator pcc 4 npcc similar clinicopathologic features overlapping survival curves 33 35 5 years p 835 less pcc 1 pcc 2 pcc 3 respectively 92 74 64 5 years p 005 combinations multivariate analysis pcc showed 50 invasive component nodal metastasis positive operative margin independent predictors conclusion pcc survival decreased progression invasive component pcc 50 invasive component clinicopathologically similar npcc although ipnb might nosologically applied pcc cases 50 invasive component present prognostic delineation suggests pcc subgroups belonged singular disease group pubmed","probabilities":0.9799733,"Title":"Prognostic delineation of papillary cholangiocarcinoma based on the invasive proportion: a single-institution study with 184 patients","Abstract":"BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a presumed precursor lesion in biliary carcinogenesis, clinicopathologically overlapping with papillary cholangiocarcinomas (PCC); however, because IPNB has no standardized definition, this relationship remains equivocal. Herein, we aimed to develop a new prognostic model for PCC by focusing on the invasive proportion. METHODS: Among 644 patients with resected cholangiocarcinoma (1998-2011), 184 (28%) had intraductal, exophytic, papillary lesions. These were divided into 4 subsets based on the invasive component: Noninvasive (PCC-1; n = 14), ≤10% (PCC-2; n = 32), 11-50% (PCC-3; n = 60), and >50% (PCC-4; n = 78). The remaining 460 were identified as non-PCCs (NPCC). RESULTS: Invasion beyond the duct wall and regional lymph node metastases were more frequent in NPCC than PCC (P < .001 for both). Five-year survival was better for PCC (55%) than NPCC (35%; P < .001), indicating the papillary component to be a significant, independent prognosticator. PCC-4 and NPCC had similar clinicopathologic features and overlapping survival curves: 33% and 35% at 5 years (P = .835), both less than those of PCC-1, PCC-2, and PCC-3 (respectively, 92%, 74%, and 64% at 5 years; P < .005 in all combinations). Multivariate analysis in PCC showed >50% invasive component, nodal metastasis, and a positive operative margin as independent predictors. CONCLUSION: PCC survival decreased with progression of the invasive component. PCC with >50% invasive component was clinicopathologically similar to NPCC. Although IPNB might be nosologically applied only for PCC cases with ≤50% invasive component, the present prognostic delineation suggests that all PCC subgroups belonged to a singular disease group.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic delineation of papillary cholangiocarcinoma based on the invasive proportion: a single-institution study with 184 patients BACKGROUND: Intraductal papillary neoplasm of the bile duct (IPNB) is a presumed precursor lesion in biliary carcinogenesis, clinicopathologically overlapping with papillary cholangiocarcinomas (PCC); however, because IPNB has no standardized definition, this relationship remains equivocal. Herein, we aimed to develop a new prognostic model for PCC by focusing on the invasive proportion. METHODS: Among 644 patients with resected cholangiocarcinoma (1998-2011), 184 (28%) had intraductal, exophytic, papillary lesions. These were divided into 4 subsets based on the invasive component: Noninvasive (PCC-1; n = 14), ≤10% (PCC-2; n = 32), 11-50% (PCC-3; n = 60), and >50% (PCC-4; n = 78). The remaining 460 were identified as non-PCCs (NPCC). RESULTS: Invasion beyond the duct wall and regional lymph node metastases were more frequent in NPCC than PCC (P < .001 for both). Five-year survival was better for PCC (55%) than NPCC (35%; P < .001), indicating the papillary component to be a significant, independent prognosticator. PCC-4 and NPCC had similar clinicopathologic features and overlapping survival curves: 33% and 35% at 5 years (P = .835), both less than those of PCC-1, PCC-2, and PCC-3 (respectively, 92%, 74%, and 64% at 5 years; P < .005 in all combinations). Multivariate analysis in PCC showed >50% invasive component, nodal metastasis, and a positive operative margin as independent predictors. CONCLUSION: PCC survival decreased with progression of the invasive component. PCC with >50% invasive component was clinicopathologically similar to NPCC. Although IPNB might be nosologically applied only for PCC cases with ≤50% invasive component, the present prognostic delineation suggests that all PCC subgroups belonged to a singular disease group. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatitis c virus infection risk malignancies hepatocellular carcinoma possible relationship objectives hcv liver tropic pro carcinogenic pathogen since recently suggested risk factor malignancies hcc aimed detect relevant studies possible association hcv infection non liver malignancies methods systematic review according prisma statement focusing following cancers lymphomas biliary ducts renal kidney pancreatic thyroid breast lung stomach colon skin oral prostate carcinomas results hcv infection resulted associated elevated incidence b cell non hodgkin lymphoma subtypes diffuse large b cell marginal zone lymphoplasmocytic follicular burkitt lymphoma geographical areas high prevalence 10 pathogen may found 2 intrahepatic extrahepatic cholangiocarcinoma 3 pancreatic cancer definitive univocal conclusions may obtained analysis relationship hcv breast renal skin oraland thyroid cancers although possible association renal skin oral thyroid malignancies hcv infection reported studies conclusions well designed large sample size studies carried different geographical areas need confirm deny results google scholar","probabilities":0.9467213,"Title":"Hepatitis C Virus Infection And Risk Of Malignancies Other Than Hepatocellular Carcinoma: Is There A Possible Relationship?","Abstract":"Objectives: HCV is a liver-tropic pro-carcinogenic pathogen. Since it\nwas recently suggested to be a risk factor for malignancies other than\nHCC, we aimed to detect relevant studies on the possible association\nbetween HCV infection and non-liver malignancies.\nMethods: A systematic review, according to PRISMA statement, focusing\non the following cancers: lymphomas, biliary ducts, renal/kidney,\npancreatic, thyroid, breast, lung, stomach, colon, skin/oral, and\nprostate-carcinomas.\nResults: HCV infection has resulted to be associated with a more elevated\nincidence of: (a) some B-cell non-Hodgkin Lymphoma subtypes\n(diffuse large B-cell-, marginal zone-, lymphoplasmocytic-,\nfollicular- and Burkitt’s- lymphoma) in geographical areas, where a\nhigh prevalence (about 10%) of this pathogen may be found; (2) intrahepatic-,\nbut not extrahepatic-cholangiocarcinoma; and (3) pancreatic\ncancer. No definitive and univocal conclusions may be obtained from\nthe analysis of relationship between HCV and breast-, renal-, skin/oraland\nthyroid-cancers, although a possible association between renal-\n, skin/oral- and thyroid malignancies and HCV infection has been reported\nby some studies.\nConclusions: Further well-designed and large sample-size studies,\ncarried out in different geographical areas are need to confirm or deny\nthese results.","Source":"Google Scholar","category":"HUMAN","training_data":"Hepatitis C Virus Infection And Risk Of Malignancies Other Than Hepatocellular Carcinoma: Is There A Possible Relationship? Objectives: HCV is a liver-tropic pro-carcinogenic pathogen. Since it\nwas recently suggested to be a risk factor for malignancies other than\nHCC, we aimed to detect relevant studies on the possible association\nbetween HCV infection and non-liver malignancies.\nMethods: A systematic review, according to PRISMA statement, focusing\non the following cancers: lymphomas, biliary ducts, renal/kidney,\npancreatic, thyroid, breast, lung, stomach, colon, skin/oral, and\nprostate-carcinomas.\nResults: HCV infection has resulted to be associated with a more elevated\nincidence of: (a) some B-cell non-Hodgkin Lymphoma subtypes\n(diffuse large B-cell-, marginal zone-, lymphoplasmocytic-,\nfollicular- and Burkitt’s- lymphoma) in geographical areas, where a\nhigh prevalence (about 10%) of this pathogen may be found; (2) intrahepatic-,\nbut not extrahepatic-cholangiocarcinoma; and (3) pancreatic\ncancer. No definitive and univocal conclusions may be obtained from\nthe analysis of relationship between HCV and breast-, renal-, skin/oraland\nthyroid-cancers, although a possible association between renal-\n, skin/oral- and thyroid malignancies and HCV infection has been reported\nby some studies.\nConclusions: Further well-designed and large sample-size studies,\ncarried out in different geographical areas are need to confirm or deny\nthese results. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"induction mkp 1 prevents cytotoxic effects pi3k inhibition hilar cholangiocarcinoma cells purpose hilar cholangiocarcinoma klatskin tumor one difficult cancers treat demonstrate activation phosphoinositide 3 kinase pi3k akt signaling critical pathway cell survival hilar cholangiocarcinoma cells however inhibition pi3k little effect hilar cholangiocarcinoma cell survival study investigated mechanism hilar cholangiocarcinoma cells resist pi3k inhibitors methods human hilar cholangiocarcinoma cells kku 100 treated pi3k inhibitors cell viability apoptosis assays performed expression mapk phosphatase mkp 1 contributes cancer cell survival response multiple stress stimuli assayed quantitative real time rt pcr western blotting addition effects mkp 1 inhibitor studied kku 100 cells treated pi3k inhibitors results incubation kku 100 cells pi3k inhibitors resulted increased expression mkp 1 furthermore found inhibition mkp 1 using sirna silencing sensitized kku 100 cells pi3k inhibitor induced apoptosis via increased phosphorylation p38 mapk conclusions results indicate concurrent inhibition pi3k mkp 1 induces apoptosis kku 100 cells simultaneous targeting pi3k pathway mkp 1 may useful approach improve therapies directed hilar cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Induction Of Mkp-1 Prevents The Cytotoxic Effects Of Pi3K Inhibition In Hilar Cholangiocarcinoma Cells","Abstract":"Purpose: Hilar cholangiocarcinoma (Klatskin tumor) is one of the most difficult cancers to treat. We demonstrate activation of phosphoinositide-3-kinase (PI3K)/Akt signaling, which is a critical pathway for cell survival, in hilar cholangiocarcinoma cells. However, inhibition of PI3K has little effect on hilar cholangiocarcinoma cell survival. In this study, we investigated the mechanism by which hilar cholangiocarcinoma cells resist PI3K inhibitors. \r\n\r\n Methods: Human hilar cholangiocarcinoma cells KKU-100 were treated with PI3K inhibitors, and cell viability and apoptosis assays were performed. The expression of a MAPK phosphatase (MKP-1) that contributes to cancer cell survival in response to multiple stress stimuli was assayed by quantitative real-time RT-PCR and western blotting. In addition, the effects of the MKP-1 inhibitor were studied in KKU-100 cells treated with PI3K inhibitors. \r\n\r\n Results: Incubation of KKU-100 cells with PI3K inhibitors resulted in increased expression of MKP-1. Furthermore, we found that inhibition of MKP-1 using siRNA silencing sensitized KKU-100 cells to PI3K inhibitor-induced apoptosis via increased phosphorylation of p38 MAPK. \r\n\r\n Conclusions: These results indicate that concurrent inhibition of PI3K and MKP-1 induces apoptosis in KKU-100 cells. Simultaneous targeting of the PI3K pathway and MKP-1 may be a useful approach to improve therapies directed against hilar cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Induction Of Mkp-1 Prevents The Cytotoxic Effects Of Pi3K Inhibition In Hilar Cholangiocarcinoma Cells Purpose: Hilar cholangiocarcinoma (Klatskin tumor) is one of the most difficult cancers to treat. We demonstrate activation of phosphoinositide-3-kinase (PI3K)/Akt signaling, which is a critical pathway for cell survival, in hilar cholangiocarcinoma cells. However, inhibition of PI3K has little effect on hilar cholangiocarcinoma cell survival. In this study, we investigated the mechanism by which hilar cholangiocarcinoma cells resist PI3K inhibitors. \r\n\r\n Methods: Human hilar cholangiocarcinoma cells KKU-100 were treated with PI3K inhibitors, and cell viability and apoptosis assays were performed. The expression of a MAPK phosphatase (MKP-1) that contributes to cancer cell survival in response to multiple stress stimuli was assayed by quantitative real-time RT-PCR and western blotting. In addition, the effects of the MKP-1 inhibitor were studied in KKU-100 cells treated with PI3K inhibitors. \r\n\r\n Results: Incubation of KKU-100 cells with PI3K inhibitors resulted in increased expression of MKP-1. Furthermore, we found that inhibition of MKP-1 using siRNA silencing sensitized KKU-100 cells to PI3K inhibitor-induced apoptosis via increased phosphorylation of p38 MAPK. \r\n\r\n Conclusions: These results indicate that concurrent inhibition of PI3K and MKP-1 induces apoptosis in KKU-100 cells. Simultaneous targeting of the PI3K pathway and MKP-1 may be a useful approach to improve therapies directed against hilar cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"effectiveness percutaneous metal stent placement cholangiocarcinoma patients midterm follow single center experience purpose patients advanced cholangiocarcinoma present high rate local complications primary aim study report clinical course advanced cholangiocarcinoma patients presented biliary obstruction treated percutaneous biliary stenting material methods patients unresectable locally advanced metastatic cholangiocarcinoma followed center period 4 years analyzed statistical analysis demographic clinical characteristics patients primary biliary drainage method metal stent occlusion rate time stent occlusion overall survival rates recorded results total 34 eligible patients analyzed 27 patients metal stent placement 27 patients formed basis study median overall survival os 6 0 months metal stent deployment bilurubin levels normalized within mean 10 days follow period 13 patients experienced metal stent occlusion median ttso 10 weeks cytotoxic chemotherapy administered 14 52 patients patients without stent dysfunction significantly higher rate chemotherapy exposure rate p 0 021 statistical analysis however failed exhibit significant effect stent dysfunction os conclusion advanced cholangiocarcinoma relief bile duct obstruction important part initial patient management study therefore described clinical value percutaneous metal stent cholangiocarcinoma patients raises question patency metal stent cholangiocarcinoma whether expect success similar success achieved pancreas carcinoma pubmed","probabilities":0.9799733,"Title":"Effectiveness of percutaneous metal stent placement in cholangiocarcinoma patients with midterm follow-up: Single center experience","Abstract":"PURPOSE: Patients with advanced cholangiocarcinoma present with high rate of local complications. The primary aim of this study is to report clinical course of advanced cholangiocarcinoma patients those who were presented with biliary obstruction and treated with percutaneous biliary stenting. MATERIAL AND METHODS: Patients with unresectable locally advanced or metastatic cholangiocarcinoma followed by our center for a period of 4 years were analyzed. For statistical analysis demographic and clinical characteristics of patients, primary biliary drainage method, metal stent occlusion rate, time to stent occlusion, and overall survival rates were recorded. RESULTS: A total of 34 eligible patients were analyzed. 27 patients had metal stent placement. These 27 patients formed the basis of this study. Median overall survival (OS) was 6.0 months. After metal stent deployment bilurubin levels were normalized within a mean of 10 days. During the follow-up period, 13 patients were experienced metal stent occlusion. Median TtSO was 10 weeks. Cytotoxic chemotherapy was administered to 14 (52%) patients. Patients without stent dysfunction had significantly higher rate of chemotherapy exposure rate (p=0.021). Statistical analysis, however, failed to exhibit significant effect of stent dysfunction on OS. CONCLUSION: In advanced cholangiocarcinoma, relief of bile duct obstruction is an important part of the initial patient management. This study therefore described the clinical value of percutaneous metal stent in cholangiocarcinoma patients and raises the question about patency of metal stent in cholangiocarcinoma whether we can expect success similar to the success achieved in pancreas carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Effectiveness of percutaneous metal stent placement in cholangiocarcinoma patients with midterm follow-up: Single center experience PURPOSE: Patients with advanced cholangiocarcinoma present with high rate of local complications. The primary aim of this study is to report clinical course of advanced cholangiocarcinoma patients those who were presented with biliary obstruction and treated with percutaneous biliary stenting. MATERIAL AND METHODS: Patients with unresectable locally advanced or metastatic cholangiocarcinoma followed by our center for a period of 4 years were analyzed. For statistical analysis demographic and clinical characteristics of patients, primary biliary drainage method, metal stent occlusion rate, time to stent occlusion, and overall survival rates were recorded. RESULTS: A total of 34 eligible patients were analyzed. 27 patients had metal stent placement. These 27 patients formed the basis of this study. Median overall survival (OS) was 6.0 months. After metal stent deployment bilurubin levels were normalized within a mean of 10 days. During the follow-up period, 13 patients were experienced metal stent occlusion. Median TtSO was 10 weeks. Cytotoxic chemotherapy was administered to 14 (52%) patients. Patients without stent dysfunction had significantly higher rate of chemotherapy exposure rate (p=0.021). Statistical analysis, however, failed to exhibit significant effect of stent dysfunction on OS. CONCLUSION: In advanced cholangiocarcinoma, relief of bile duct obstruction is an important part of the initial patient management. This study therefore described the clinical value of percutaneous metal stent in cholangiocarcinoma patients and raises the question about patency of metal stent in cholangiocarcinoma whether we can expect success similar to the success achieved in pancreas carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"perioperative blood transfusion poor prognostic factor aggressive surgical resection hilar cholangiocarcinoma background blood transfusion linked negative outcome malignant tumors aim study evaluate aggressive surgical resection hilar cholangiocarcinoma hcca assess impact perioperative blood transfusion long term survival methods sixty six consecutive major hepatectomies en bloc resection caudate lobe extrahepatic bile duct hcca performed using macroscopically curative resection institute 2002 2012 clinicopathologic factors recurrence survival retrospectively assessed results overall survival rates 1 3 5 years 86 7 47 3 35 7 respectively univariate analysis perioperative blood transfusion histological positive margin two several variables found significant prognostic factors recurrence survival p 0 05 multivariate analysis perioperative blood transfusion independently associated recurrence hazard ratio hr 2 839 95 confidence interval ci 1 370 5 884 p 0 005 perioperative blood transfusion hr 3 383 95 ci 1 499 7 637 p 0 003 r1 resection hr 3 125 95 ci 1 025 9 530 p 0 045 independent risk factors poor survival conclusions perioperative blood transfusion strong predictor poor survival radical hepatectomy hcca suggest circumvention perioperative blood transfusion play important role long term survival patients hcca pubmed","probabilities":0.9799733,"Title":"Perioperative blood transfusion as a poor prognostic factor after aggressive surgical resection for hilar cholangiocarcinoma","Abstract":"BACKGROUND: Blood transfusion is linked to a negative outcome for malignant tumors. The aim of this study was to evaluate aggressive surgical resection for hilar cholangiocarcinoma (HCCA) and assess the impact of perioperative blood transfusion on long-term survival. METHODS: Sixty-six consecutive major hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile duct for HCCA were performed using macroscopically curative resection at our institute from 2002 to 2012. Clinicopathologic factors for recurrence and survival were retrospectively assessed. RESULTS: Overall survival rates at 1, 3, and 5 years were 86.7, 47.3, and 35.7 %, respectively. In univariate analysis, perioperative blood transfusion and a histological positive margin were two of several variables found to be significant prognostic factors for recurrence or survival (P<0.05). In multivariate analysis, only perioperative blood transfusion was independently associated with recurrence (hazard ratio (HR)=2.839 (95 % confidence interval (CI), 1.370-5.884), P=0.005), while perioperative blood transfusion (HR=3.383 (95 % CI, 1.499-7.637), P=0.003) and R1 resection (HR=3.125 (95 % CI, 1.025-9.530), P=0.045) were independent risk factors for poor survival. CONCLUSIONS: Perioperative blood transfusion is a strong predictor of poor survival after radical hepatectomy for HCCA. We suggest that circumvention of perioperative blood transfusion can play an important role in long-term survival for patients with HCCA.","Source":"PubMed","category":"HUMAN","training_data":"Perioperative blood transfusion as a poor prognostic factor after aggressive surgical resection for hilar cholangiocarcinoma BACKGROUND: Blood transfusion is linked to a negative outcome for malignant tumors. The aim of this study was to evaluate aggressive surgical resection for hilar cholangiocarcinoma (HCCA) and assess the impact of perioperative blood transfusion on long-term survival. METHODS: Sixty-six consecutive major hepatectomies with en bloc resection of the caudate lobe and extrahepatic bile duct for HCCA were performed using macroscopically curative resection at our institute from 2002 to 2012. Clinicopathologic factors for recurrence and survival were retrospectively assessed. RESULTS: Overall survival rates at 1, 3, and 5 years were 86.7, 47.3, and 35.7 %, respectively. In univariate analysis, perioperative blood transfusion and a histological positive margin were two of several variables found to be significant prognostic factors for recurrence or survival (P<0.05). In multivariate analysis, only perioperative blood transfusion was independently associated with recurrence (hazard ratio (HR)=2.839 (95 % confidence interval (CI), 1.370-5.884), P=0.005), while perioperative blood transfusion (HR=3.383 (95 % CI, 1.499-7.637), P=0.003) and R1 resection (HR=3.125 (95 % CI, 1.025-9.530), P=0.045) were independent risk factors for poor survival. CONCLUSIONS: Perioperative blood transfusion is a strong predictor of poor survival after radical hepatectomy for HCCA. We suggest that circumvention of perioperative blood transfusion can play an important role in long-term survival for patients with HCCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"antineutrophil cytoplasmic antibodies bile associated disease activity primary sclerosing cholangitis objective primary sclerosing cholangitis psc autoimmune cholestatic liver disease unknown etiology role antineutrophil cytoplasmic antibodies ancas serum patients psc remains unclear hypothesized anca maybe detectable bile potentially providing diagnostic prognostic information methods serum andbile prospectively collected endoscopic retrograde cholangiography erc 72 patients psc nonpsc obstructive biliary diseases anca measurements performed indirect immuno uorescence iif results immunoglobulin g igg anca detected signi cantly often bile psc patients 15 39 38 without 2 33 6 p 0 001 igg anca bile associated ten times higher risk psc p 0 005 addition igg anca positivity bile associated presence dominant strictures p 0 03 cholangiographic severity p 0 004 number erc p 0 01 interventions performed p 0 03 however igg anca bile correlate transplantation cholangiocarcinoma death association observed anca positivity sera ana asca positivity sera bile mentioned clinical features conclusions presence anca bile patients psc novel nding highly suggestive psc biliary igg anca correlates severity bile duct strictures ensuing number ercs interventions therefore positive anca status bile may serve diagnostic prognostic marker disease progression biliary complications google scholar","probabilities":0.9799733,"Title":"Antineutrophil Cytoplasmic Antibodies In Bile Are Associated With Disease Activity In Primary Sclerosing Cholangitis","Abstract":"Objective. Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology. The role of antineutrophil cytoplasmic antibodies (ANCAs) in the serum of patients with PSC remains unclear. We hypothesized that ANCA maybe detectable in bile,potentially providing diagnostic and prognostic information. Methods.Serum andbile were prospectively collected during endoscopic retrograde cholangiography (ERC) in 72 patients with PSC and other nonPSC obstructive biliary diseases. ANCA measurements were performed by indirect immunofluorescence (IIF). Results. Immunoglobulin G (IgG) ANCA was detected significantly more often in the bile of PSC patients (15/39; 38%) than without (2/33; 6%) (p = 0.001). IgG ANCA in bile was associated with a ten times higher risk of PSC (p = 0.005). In addition, IgG ANCA positivity in bile was associated with the presence of dominant strictures (p = 0.03), cholangiographic severity (p= 0.004), number of ERC (p=0.01) and interventions performed (p =0.03). However, IgG ANCA in bile did not correlate with transplantation, cholangiocarcinoma or death. No association was observed between ANCA positivity in sera and ANA and ASCA positivity in sera or bile with the above-mentioned clinical features. Conclusions. The presence of ANCA in the bile of patients with PSC is a novel finding and highly suggestive of PSC. Biliary IgG ANCA correlates with the severity of bile duct strictures and the ensuing number of ERCs and interventions. Therefore, a positive ANCA status in bile may serve as a diagnostic and prognostic marker of the disease progression and biliary complications.","Source":"Google Scholar","category":"HUMAN","training_data":"Antineutrophil Cytoplasmic Antibodies In Bile Are Associated With Disease Activity In Primary Sclerosing Cholangitis Objective. Primary sclerosing cholangitis (PSC) is an autoimmune cholestatic liver disease of unknown etiology. The role of antineutrophil cytoplasmic antibodies (ANCAs) in the serum of patients with PSC remains unclear. We hypothesized that ANCA maybe detectable in bile,potentially providing diagnostic and prognostic information. Methods.Serum andbile were prospectively collected during endoscopic retrograde cholangiography (ERC) in 72 patients with PSC and other nonPSC obstructive biliary diseases. ANCA measurements were performed by indirect immunofluorescence (IIF). Results. Immunoglobulin G (IgG) ANCA was detected significantly more often in the bile of PSC patients (15/39; 38%) than without (2/33; 6%) (p = 0.001). IgG ANCA in bile was associated with a ten times higher risk of PSC (p = 0.005). In addition, IgG ANCA positivity in bile was associated with the presence of dominant strictures (p = 0.03), cholangiographic severity (p= 0.004), number of ERC (p=0.01) and interventions performed (p =0.03). However, IgG ANCA in bile did not correlate with transplantation, cholangiocarcinoma or death. No association was observed between ANCA positivity in sera and ANA and ASCA positivity in sera or bile with the above-mentioned clinical features. Conclusions. The presence of ANCA in the bile of patients with PSC is a novel finding and highly suggestive of PSC. Biliary IgG ANCA correlates with the severity of bile duct strictures and the ensuing number of ERCs and interventions. Therefore, a positive ANCA status in bile may serve as a diagnostic and prognostic marker of the disease progression and biliary complications. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"feasibility study gemcitabine 1 leucovorin combination therapy gsl advanced biliary tract cancer objective gemcitabine cisplatin gc combination chemotherapy current standard care patients advanced biliary tract cancer btc recently randomized controlled trial showed non inferiority overall survival gemcitabine 1 gs compared gc leucovorin known enhance activity 1 conducted study evaluate feasibility combination therapy gemcitabine 1 leucovorin gsl methods advanced btc patients without prior treatment surgery adjuvant chemotherapy eligible study gemcitabine administered dose 1000 mg m 2 day 1 oral 1 dose 40 mg m 2 oral leucovorin dose 25 mg twice daily days 1 7 every 2 weeks primary endpoint pfs secondary endpoints included os objective tumour response safety results june 2013 december 2015 20 patients advanced btc 12 gallbladder 4 extrahepatic 2 intrahepatic 2 ampulla including 16 unresectable disease 4 recurrent disease enroled median pfs os 5 5 95 confidence interval ci 1 8 reached 16 0 95 ci 6 4 20 8 months respectively partial response achieved 3 15 stable disease 8 40 giving disease control rate 55 major grade 3 4 toxicities included neutropenia 30 anaemia 5 stomatitis 15 diarrhoea 15 anorexia 10 treatment related deaths conclusions study showed feasibility potential efficacy gsl first line treatment patients advanced btc pubmed","probabilities":0.9799733,"Title":"A feasibility study of gemcitabine, S-1 and leucovorin combination therapy (GSL) for advanced biliary tract cancer","Abstract":"Objective: Gemcitabine and cisplatin (GC) combination chemotherapy is the current standard of care for patients with advanced biliary tract cancer (BTC). Recently, a randomized controlled trial showed the non-inferiority in overall survival of gemcitabine and S-1 (GS) compared to GC. Because leucovorin is known to enhance the activity of S-1, we conducted this study to evaluate the feasibility of combination therapy of gemcitabine, S-1 and leucovorin (GSL). Methods: Advanced BTC patients without prior treatment other than surgery or adjuvant chemotherapy were eligible to this study. Gemcitabine was administered at a dose of 1000 mg/m(2) on day 1, and oral S-1 at a dose of 40 mg/m(2) and oral leucovorin at a dose of 25 mg twice daily on days 1-7, every 2 weeks. The primary endpoint was PFS and the secondary endpoints included OS, objective tumour response and the safety. Results: Between June 2013 and December 2015, 20 patients with advanced BTC (12 gallbladder, 4 extrahepatic, 2 intrahepatic, 2 ampulla) including 16 unresectable disease and 4 recurrent disease were enroled. The median PFS and OS were 5.5 (95% confidence interval [CI], 1.8 - not reached) and 16.0 (95% CI, 6.4-20.8) months, respectively. A partial response was achieved in 3 (15%) and stable disease in 8 (40%), giving a disease control rate of 55%. Major grade 3/4 toxicities included neutropenia (30%), anaemia (5%), stomatitis (15%), diarrhoea (15%) and anorexia (10%). There were no treatment-related deaths. Conclusions: This study showed the feasibility and potential efficacy of GSL as a first-line treatment in patients with advanced BTC.","Source":"PubMed","category":"HUMAN","training_data":"A feasibility study of gemcitabine, S-1 and leucovorin combination therapy (GSL) for advanced biliary tract cancer Objective: Gemcitabine and cisplatin (GC) combination chemotherapy is the current standard of care for patients with advanced biliary tract cancer (BTC). Recently, a randomized controlled trial showed the non-inferiority in overall survival of gemcitabine and S-1 (GS) compared to GC. Because leucovorin is known to enhance the activity of S-1, we conducted this study to evaluate the feasibility of combination therapy of gemcitabine, S-1 and leucovorin (GSL). Methods: Advanced BTC patients without prior treatment other than surgery or adjuvant chemotherapy were eligible to this study. Gemcitabine was administered at a dose of 1000 mg/m(2) on day 1, and oral S-1 at a dose of 40 mg/m(2) and oral leucovorin at a dose of 25 mg twice daily on days 1-7, every 2 weeks. The primary endpoint was PFS and the secondary endpoints included OS, objective tumour response and the safety. Results: Between June 2013 and December 2015, 20 patients with advanced BTC (12 gallbladder, 4 extrahepatic, 2 intrahepatic, 2 ampulla) including 16 unresectable disease and 4 recurrent disease were enroled. The median PFS and OS were 5.5 (95% confidence interval [CI], 1.8 - not reached) and 16.0 (95% CI, 6.4-20.8) months, respectively. A partial response was achieved in 3 (15%) and stable disease in 8 (40%), giving a disease control rate of 55%. Major grade 3/4 toxicities included neutropenia (30%), anaemia (5%), stomatitis (15%), diarrhoea (15%) and anorexia (10%). There were no treatment-related deaths. Conclusions: This study showed the feasibility and potential efficacy of GSL as a first-line treatment in patients with advanced BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"liver transplantation hilar cholangiocarcinoma single centre experience background cholangiocarcinoma infrequent malignancy often unresectable time diagnosis liver transplantation may offer chance cure results past disappointing prompting transplant centres adopt multimodal treatment protocols extreme patient selection purpose study designed evaluate outcome patients irresectable hilar cholangiocarcinoma undergoing liver transplantation order determine criteria patient selection methods reviewed prospective cancer registry patients hilar cholangiocarcinoma treated transplantation since 1997 data evaluated regarding tumour location stage overall survival recurrence rates prognostic factors results liver transplantation lymphadenectomy realised 16 patients hilar cholangiocarcinoma seven patients received living donor graft lymph node metastases found eight patients median 13 harvested nodes statistically significant negative impact overall survival irrespective tumour size one patient underwent neoadjuvant brachytherapy developed fatal septic complications 3 5 year survival rates 63 50 lymph node negative patients without neoadjuvant treatment conclusions acceptable survival rates achieved transplantation hilar cholangiocarcinoma lymph node metastases exclusion criterion recommend staging laparotomy lymphadenectomy along common hepatic artery prior liver transplantation pubmed","probabilities":0.9799733,"Title":"Liver transplantation for hilar cholangiocarcinoma--a single-centre experience","Abstract":"BACKGROUND: Cholangiocarcinoma is an infrequent malignancy, often unresectable at the time of diagnosis. Liver transplantation may offer a chance for cure, but results in the past have been disappointing, prompting transplant centres to adopt multimodal treatment protocols and extreme patient selection. PURPOSE: This study was designed to evaluate the outcome of patients with irresectable hilar cholangiocarcinoma undergoing liver transplantation in order to determine criteria for patient selection. METHODS: We reviewed our prospective cancer registry for patients with hilar cholangiocarcinoma treated by transplantation since 1997. Data were evaluated regarding tumour location, stage, overall survival, recurrence rates and prognostic factors. RESULTS: Liver transplantation with lymphadenectomy was realised in 16 patients with hilar cholangiocarcinoma. Seven patients received a living donor graft. Lymph node metastases were found in eight patients with a median of 13 harvested nodes and had a statistically significant negative impact on overall survival irrespective of tumour size. Only one patient underwent neoadjuvant brachytherapy and developed fatal septic complications; 3- and 5-year survival rates were 63 and 50 % in lymph node-negative patients without neoadjuvant treatment. CONCLUSIONS: Acceptable survival rates can be achieved by transplantation for hilar cholangiocarcinoma with lymph node metastases as the only exclusion criterion. We recommend staging laparotomy with lymphadenectomy along the common hepatic artery prior to liver transplantation.","Source":"PubMed","category":"HUMAN","training_data":"Liver transplantation for hilar cholangiocarcinoma--a single-centre experience BACKGROUND: Cholangiocarcinoma is an infrequent malignancy, often unresectable at the time of diagnosis. Liver transplantation may offer a chance for cure, but results in the past have been disappointing, prompting transplant centres to adopt multimodal treatment protocols and extreme patient selection. PURPOSE: This study was designed to evaluate the outcome of patients with irresectable hilar cholangiocarcinoma undergoing liver transplantation in order to determine criteria for patient selection. METHODS: We reviewed our prospective cancer registry for patients with hilar cholangiocarcinoma treated by transplantation since 1997. Data were evaluated regarding tumour location, stage, overall survival, recurrence rates and prognostic factors. RESULTS: Liver transplantation with lymphadenectomy was realised in 16 patients with hilar cholangiocarcinoma. Seven patients received a living donor graft. Lymph node metastases were found in eight patients with a median of 13 harvested nodes and had a statistically significant negative impact on overall survival irrespective of tumour size. Only one patient underwent neoadjuvant brachytherapy and developed fatal septic complications; 3- and 5-year survival rates were 63 and 50 % in lymph node-negative patients without neoadjuvant treatment. CONCLUSIONS: Acceptable survival rates can be achieved by transplantation for hilar cholangiocarcinoma with lymph node metastases as the only exclusion criterion. We recommend staging laparotomy with lymphadenectomy along the common hepatic artery prior to liver transplantation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"predictive factors cholangiocarcinoma associated hepatolithiasis determined basis japanese multicenter study aim aim study delineate predictive factors cholangiocarcinoma patients hepatolithiasis establish optimal management hepatolithiasis viewpoint carcinogenesis basis japanese nationwide survey hepatolithiasis methods hepatolithiasis research group organized 2006 ministry health labour welfare japan conducted nationwide survey research group collected data 336 cases hepatolithiasis 2006 cross sectional survey involving 2592 institutions japan predictive factors cholangiocarcinoma associated hepatolithiasis analyzed univariate multivariate analyses clinicopathological therapeutic factors results twenty three patients cholangiocarcinoma histories choledocoenterostomy liver atrophy found significantly predictive factors multivariate analysis 87 5 cases cholangiocarcinoma liver atrophy cholangiocarcinoma located atrophic lobes method reconstruction affect incidence cholangiocarcinoma choledochojejunostomy vs choledochoduodenostomy side end vs side side anastomosis conclusions choledocoenterostomy liver atrophy may increase risk developing cholangiocarcinoma choledocoenterostomy thus contraindicated patients hepatolithiasis aggressive resection strategy recommended atrophic segment stn","probabilities":0.9799733,"Title":"Predictive Factors For Cholangiocarcinoma Associated With Hepatolithiasis Determined On The Basis Of Japanese Multicenter Study","Abstract":"Aim: The aim of this study was to delineate predictive factors for cholangiocarcinoma in patients with hepatolithiasis, and to establish optimal management for hepatolithiasis from the viewpoint of carcinogenesis on the basis of a Japanese nationwide survey for hepatolithiasis. \r\n\r\n Methods: The Hepatolithiasis Research Group was organized in 2006 by the Ministry of Health, Labour and Welfare of Japan, and conducted a nationwide survey. The research group collected data on 336 cases of hepatolithiasis in 2006, in a cross-sectional survey involving 2592 institutions in Japan. Predictive factors for cholangiocarcinoma associated with hepatolithiasis were analyzed by univariate and multivariate analyses of clinicopathological and therapeutic factors. \r\n\r\n Results: Twenty-three patients had cholangiocarcinoma. Histories of choledocoenterostomy and liver atrophy were found to be significantly predictive factors by multivariate analysis. In 87.5% of cases of cholangiocarcinoma with liver atrophy, cholangiocarcinoma was located in the atrophic lobes. The method of reconstruction did not affect the incidence of cholangiocarcinoma (choledochojejunostomy vs. choledochoduodenostomy; side-to-end vs. side-to-side anastomosis). \r\n\r\n Conclusions: Choledocoenterostomy and liver atrophy may increase the risk of developing cholangiocarcinoma. Choledocoenterostomy is thus contraindicated in patients with hepatolithiasis. An aggressive resection strategy is recommended for an atrophic segment.","Source":"STN","category":"HUMAN","training_data":"Predictive Factors For Cholangiocarcinoma Associated With Hepatolithiasis Determined On The Basis Of Japanese Multicenter Study Aim: The aim of this study was to delineate predictive factors for cholangiocarcinoma in patients with hepatolithiasis, and to establish optimal management for hepatolithiasis from the viewpoint of carcinogenesis on the basis of a Japanese nationwide survey for hepatolithiasis. \r\n\r\n Methods: The Hepatolithiasis Research Group was organized in 2006 by the Ministry of Health, Labour and Welfare of Japan, and conducted a nationwide survey. The research group collected data on 336 cases of hepatolithiasis in 2006, in a cross-sectional survey involving 2592 institutions in Japan. Predictive factors for cholangiocarcinoma associated with hepatolithiasis were analyzed by univariate and multivariate analyses of clinicopathological and therapeutic factors. \r\n\r\n Results: Twenty-three patients had cholangiocarcinoma. Histories of choledocoenterostomy and liver atrophy were found to be significantly predictive factors by multivariate analysis. In 87.5% of cases of cholangiocarcinoma with liver atrophy, cholangiocarcinoma was located in the atrophic lobes. The method of reconstruction did not affect the incidence of cholangiocarcinoma (choledochojejunostomy vs. choledochoduodenostomy; side-to-end vs. side-to-side anastomosis). \r\n\r\n Conclusions: Choledocoenterostomy and liver atrophy may increase the risk of developing cholangiocarcinoma. Choledocoenterostomy is thus contraindicated in patients with hepatolithiasis. An aggressive resection strategy is recommended for an atrophic segment. STN","prediction_labels":"HUMAN"},{"cleaned":"routine histopathological gallbladder examination necessary cholecystectomy evaluation results 1366 cholecystectomy specimens single center objective aimed evaluate results routine histopathological examination cholecystectomy investigate necessity routine histopathologic examination cholecystectomy methods study designed retrospectively 1366 patients underwent laparoscopic open cholecystectomy center pre diagnosis benign gallbladder disease november 2011 may 2017were included study patients demographic data pathologic results macroscopic appearance specimen cancer staging recorded distribution frequency pathologic diagnoses prevalence incidental gallbladder cancer gbc evaluated pathologic findings compared terms age groups gender relations results number patients included study 1 366 1 303 patients 95 diagnosed chronic cholecystitis 39 3 acute cholecystitis 7 0 5 gbc 17 1 5 diagnoses patients statistical significance found groups terms mean age p 0 0002 comparisons groups terms cholesterolysis statistically significant p 0 0003 significant relationship mucosa atrophy gender p 0 001 discussion histopathological spectrum gallbladder quite extensive incidental gbc may detected preoperative imaging methods incidental gbc usually asymptomatic t2 t3 t4 gbc also encountered study patients need additional operations absence routine histopathologic examination metastatic advanced gbc may encountered treatment plans make thus recommend routine histopathological examination google scholar","probabilities":0.9799733,"Title":"Is Routine Histopathological Gallbladder Examination Necessary After Cholecystectomy? Evaluation Of The Results Of 1366 Cholecystectomy Specimens In Single Center","Abstract":"Objective: it was aimed to evaluate the results of routine histopathological examination after cholecystectomy and to investigate the necessity of routine histopathologic examination after cholecystectomy.\n\n Methods: The study was designed retrospectively. 1366 patients who underwent laparoscopic and open cholecystectomy at our center with pre-diagnosis of benign gallbladder disease between November 2011 and May 2017were included in the study. Patients' demographic data, pathologic results, macroscopic appearance of the specimen, and cancer staging were recorded. The distribution and frequency of pathologic diagnoses and the prevalence of incidental gallbladder cancer (GBC) were evaluated. Pathologic findings were compared in terms of age groups and gender relations.\n\nResults: The number of patients included in the study was 1,366. 1,303 patients (95%) were diagnosed with chronic cholecystitis, 39 (3%) with acute cholecystitis, 7 (0.5%) with GBC, and 17 (1.5%) with other diagnoses of the patients. Statistical significance was found between the groups in terms of the mean age (p = 0.0002). Comparisons between groups in terms of cholesterolysis were statistically significant (p = 0.0003). There was a significant relationship between mucosa atrophy and gender (p = 0.001).\n\nDiscussion: The histopathological spectrum of gallbladder is quite extensive. Incidental GBC may not be detected by preoperative imaging methods. Incidental GBC are usually asymptomatic. T2, T3 and T4 GBC were also encountered in our study. All of these patients need additional operations. In the absence of routine histopathologic examination, metastatic advanced GBC may be encountered because no treatment plans could make. Thus, we do recommend routine histopathological examination.","Source":"Google Scholar","category":"HUMAN","training_data":"Is Routine Histopathological Gallbladder Examination Necessary After Cholecystectomy? Evaluation Of The Results Of 1366 Cholecystectomy Specimens In Single Center Objective: it was aimed to evaluate the results of routine histopathological examination after cholecystectomy and to investigate the necessity of routine histopathologic examination after cholecystectomy.\n\n Methods: The study was designed retrospectively. 1366 patients who underwent laparoscopic and open cholecystectomy at our center with pre-diagnosis of benign gallbladder disease between November 2011 and May 2017were included in the study. Patients' demographic data, pathologic results, macroscopic appearance of the specimen, and cancer staging were recorded. The distribution and frequency of pathologic diagnoses and the prevalence of incidental gallbladder cancer (GBC) were evaluated. Pathologic findings were compared in terms of age groups and gender relations.\n\nResults: The number of patients included in the study was 1,366. 1,303 patients (95%) were diagnosed with chronic cholecystitis, 39 (3%) with acute cholecystitis, 7 (0.5%) with GBC, and 17 (1.5%) with other diagnoses of the patients. Statistical significance was found between the groups in terms of the mean age (p = 0.0002). Comparisons between groups in terms of cholesterolysis were statistically significant (p = 0.0003). There was a significant relationship between mucosa atrophy and gender (p = 0.001).\n\nDiscussion: The histopathological spectrum of gallbladder is quite extensive. Incidental GBC may not be detected by preoperative imaging methods. Incidental GBC are usually asymptomatic. T2, T3 and T4 GBC were also encountered in our study. All of these patients need additional operations. In the absence of routine histopathologic examination, metastatic advanced GBC may be encountered because no treatment plans could make. Thus, we do recommend routine histopathological examination. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors associated preoperative clinicophysiological outcomes distal cholangiocarcinoma background aims although biliary tract cancer generally associated high mortality rate patients distal cholangiocarcinoma better prognoses compared periampullary cancer study aimed determine preoperative clinicophysiological factors predictive survival recurrence patients distal cholangiocarcinoma methods forty five patients 34 men distal cholangiocarcinoma underwent pancreaticoduodenectomy 2005 2013 examined retrospectively center associated hospitals clinicophysiological parameters included predictors overall survival os kaplan meier survival curves generated compared using log rank tests cox proportional hazard multivariate analyses performed results mean patient age 68 8 years range 54 81 years patients median os duration 43 months 1 3 5 year os rates 91 1 61 1 40 4 respectively univariate analyses indicated body mass index c reactive protein crp level carcinoembryonic antigen level independent prognostic factors os however crp level remained independent prognostic factor multivariate analysis conclusions crp level 0 3 mg dl predictive better outcome among patients distal cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic Factors Associated with Preoperative Clinicophysiological Outcomes of Distal Cholangiocarcinoma","Abstract":"BACKGROUND/AIMS: Although biliary tract cancer is generally associated with a high mortality rate, patients with distal cholangiocarcinoma have better prognoses, compared to those with periampullary cancer. This study aimed to determine the preoperative clinicophysiological factors predictive of survival and recurrence in patients with distal cholangiocarcinoma. METHODS: Forty-five patients (34 men) with distal cholangiocarcinoma who underwent pancreaticoduodenectomy between 2005 and 2013 were examined retrospectively at our center and associated hospitals. Clinicophysiological parameters included predictors of overall survival (OS). Kaplan-Meier survival curves were generated and compared using log-rank tests, and Cox proportional hazard multivariate analyses were performed. RESULTS: The mean patient age was 68.8 years (range 54-81 years). Patients had a median OS duration of 43 months, and 1-, 3-, and 5-year OS rates of 91.1, 61.1, and 40.4%, respectively. Univariate analyses indicated that the body mass index, C-reactive protein (CRP) level, and carcinoembryonic antigen level were independent prognostic factors for OS; however, only the CRP level remained an independent prognostic factor in a multivariate analysis. CONCLUSIONS: A CRP level <0.3 mg/dL was predictive of a better outcome among patients with distal cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Factors Associated with Preoperative Clinicophysiological Outcomes of Distal Cholangiocarcinoma BACKGROUND/AIMS: Although biliary tract cancer is generally associated with a high mortality rate, patients with distal cholangiocarcinoma have better prognoses, compared to those with periampullary cancer. This study aimed to determine the preoperative clinicophysiological factors predictive of survival and recurrence in patients with distal cholangiocarcinoma. METHODS: Forty-five patients (34 men) with distal cholangiocarcinoma who underwent pancreaticoduodenectomy between 2005 and 2013 were examined retrospectively at our center and associated hospitals. Clinicophysiological parameters included predictors of overall survival (OS). Kaplan-Meier survival curves were generated and compared using log-rank tests, and Cox proportional hazard multivariate analyses were performed. RESULTS: The mean patient age was 68.8 years (range 54-81 years). Patients had a median OS duration of 43 months, and 1-, 3-, and 5-year OS rates of 91.1, 61.1, and 40.4%, respectively. Univariate analyses indicated that the body mass index, C-reactive protein (CRP) level, and carcinoembryonic antigen level were independent prognostic factors for OS; however, only the CRP level remained an independent prognostic factor in a multivariate analysis. CONCLUSIONS: A CRP level <0.3 mg/dL was predictive of a better outcome among patients with distal cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"screening cholangiocarcinoma psc patients prolong survival single center cohort study background little data exists factors associated cholangiocarcinoma cca screening tests useful early detection patients psc aim identify characteristics associated cca utility commonly used screening tests methods analyzed characteristics patients psc seen institution 2004 2008 also analyzed screening modalities used detection cca patients diagnosed psc followed either diagnosis cca liver transplantation death occurred results 101 patients 69 males mean age 53 6 15 72 years included 87 patients white 13 patients black mean serum creatinine 0 90 0 43 mean inr 1 13 0 29 mean bilirubin 3 36 4 67 mean meld score 10 83 4 92 mean ca 19 9 level 129 95 490 72 study period 6 patients 5 94 diagnosed cca patients received mean number 1 65 mris 0 93 ercps 0 34 ct scans 0 69 ultrasounds screening tests observation period 4 patients found cca mri 2 diagnosed biliary aspirate brushings group cca slightly older 63 5 years vs 53 0 years p 0 025 significant difference creatinine levels 1 42 vs 0 87 p 0 46 bilirubin levels 5 34 vs 3 26 p 0 39 inr 1 16 vs 1 13 p 0 75 cca slightly higher meld score 14 26 vs 10 62 difference significant p 0 335 expected ca 19 9 levels appeared higher among cca group significantlydifferent 148 5vs89 4 p 0 63 therewerenoindependentlypredictedfactors associated development cca kaplan meier survival analysis oneyear survival patients cca statistically different without cca 94 5 vs 77 log rank 0 01 multivariate one year survival model none imaging modalities studied independent predictors diagnosis cca patients without cca underwent mri mrcps c scans total imaging tests conclusion using clinical characteristics stratify patients psc risk cca remains problematic parameters found impact risk using imaging techniques screen cca appear improve survival google scholar","probabilities":0.9799733,"Title":"Screening For Cholangiocarcinoma In Psc Patients Does Not Prolong Survival: A Single Center Cohort Study","Abstract":"Background: Little data exists on factors associated with cholangiocarcinoma (CCA) and screening tests useful for early detection in patients with PSC. Our aim was to identify characteristics associated with CCA and the utility of commonly used screening tests. Methods: We analyzed the characteristics of patients with PSC seen at our institution from 2004-2008. We also analyzed screening modalities used for detection of CCA. Patients diagnosed with PSC were followed until either diagnosis of CCA, liver transplantation, or death occurred. Results: 101 patients (69 males), mean age was 53.6 ± 15.72 years were included. 87 patients were white, 13 patients were black. Mean serum creatinine was 0.90 ± 0.43. Mean INR was 1.13 ± 0.29. Mean bilirubin was 3.36 ± 4.67. Mean MELD score was 10.83 ± 4.92. Mean CA 19-9 level was 129.95 ± 490.72. Over the study period, 6 patients (5.94%) were diagnosed with CCA. Patients received a mean number of 1.65 MRIs, 0.93 ERCPs, 0.34 CT scans, and 0.69 ultrasounds as screening tests during the observation period. 4 patients were found to have CCA on MRI, while 2 were diagnosed by biliary aspirate or brushings. The group with CCA was slightly older (63.5 years vs 53.0 years, p= 0.025). There was no significant difference in creatinine levels (1.42 vs 0.87, p=0.46), bilirubin levels (5.34 vs 3.26, p=0.39) or INR (1.16 vs 1.13, p=0.75). Those with CCA had a slightly higher MELD score (14.26 vs 10.62), but the difference was not significant (p= 0.335). As expected, CA 19-9 levels appeared higher among the CCA group, but were not significantlydifferent(148.5vs89.4,p=0.63).Therewerenoindependentlypredictedfactors that were associated with the development of CCA. In Kaplan-Meier survival analysis, oneyear survival in patients with CCA was statistically different than those without CCA (94.5% vs 77%, log rank = 0.01). In a multivariate one-year survival model, none of the imaging modalities studied were independent predictors of the diagnosis of CCA. Patients without CCA underwent more MRI/MRCPs, C T scans, and total imaging tests. Conclusion: Using clinical characteristics to stratify patients with PSC at risk for CCA remains problematic, as no parameters were found to impact risk. Using imaging techniques to screen for CCA did not appear to improve survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Screening For Cholangiocarcinoma In Psc Patients Does Not Prolong Survival: A Single Center Cohort Study Background: Little data exists on factors associated with cholangiocarcinoma (CCA) and screening tests useful for early detection in patients with PSC. Our aim was to identify characteristics associated with CCA and the utility of commonly used screening tests. Methods: We analyzed the characteristics of patients with PSC seen at our institution from 2004-2008. We also analyzed screening modalities used for detection of CCA. Patients diagnosed with PSC were followed until either diagnosis of CCA, liver transplantation, or death occurred. Results: 101 patients (69 males), mean age was 53.6 ± 15.72 years were included. 87 patients were white, 13 patients were black. Mean serum creatinine was 0.90 ± 0.43. Mean INR was 1.13 ± 0.29. Mean bilirubin was 3.36 ± 4.67. Mean MELD score was 10.83 ± 4.92. Mean CA 19-9 level was 129.95 ± 490.72. Over the study period, 6 patients (5.94%) were diagnosed with CCA. Patients received a mean number of 1.65 MRIs, 0.93 ERCPs, 0.34 CT scans, and 0.69 ultrasounds as screening tests during the observation period. 4 patients were found to have CCA on MRI, while 2 were diagnosed by biliary aspirate or brushings. The group with CCA was slightly older (63.5 years vs 53.0 years, p= 0.025). There was no significant difference in creatinine levels (1.42 vs 0.87, p=0.46), bilirubin levels (5.34 vs 3.26, p=0.39) or INR (1.16 vs 1.13, p=0.75). Those with CCA had a slightly higher MELD score (14.26 vs 10.62), but the difference was not significant (p= 0.335). As expected, CA 19-9 levels appeared higher among the CCA group, but were not significantlydifferent(148.5vs89.4,p=0.63).Therewerenoindependentlypredictedfactors that were associated with the development of CCA. In Kaplan-Meier survival analysis, oneyear survival in patients with CCA was statistically different than those without CCA (94.5% vs 77%, log rank = 0.01). In a multivariate one-year survival model, none of the imaging modalities studied were independent predictors of the diagnosis of CCA. Patients without CCA underwent more MRI/MRCPs, C T scans, and total imaging tests. Conclusion: Using clinical characteristics to stratify patients with PSC at risk for CCA remains problematic, as no parameters were found to impact risk. Using imaging techniques to screen for CCA did not appear to improve survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic role soluble transforming growth factor stgfb soluble programmed death ligand 1 spdl1 biliary tract cancer patients treated binimetinib capecitabine background previously reported soluble programmed death ligand 1 spd l1 pre chemotherapy indicated prognostic value overall survival os dynamics spd l1 palliative chemotherapy correlated disease burden biliary tract cancer btc transforming growth factor tgf attenuates tumor response pd1 pd l1 inhibitors strategy dual targeting pd1 pd l1 tgf investigation study aimed evaluate association soluble tgf stgf spd l1 dynamics chemotherapy prognostic role btc methods study population consisted 90 btc patients treated first line chemotherapy blood samples pre post chemotherapy disease progression pd prospectively collected plasma stgf spd l1 levels measured using enzyme linked immunosorbent assay results median progression free survival pfs os patients 6 9 months m 95 ci 5 2 8 6 11 5 m 95 ci 9 4 13 6 best response cr 7 7 8 pr 20 22 2 sd 52 57 8 pd 11 patients 12 2 mean baseline stgf spd l1 16 4 ng ml 1 3 ng ml positive association stgf spd l1 terms baseline levels changes chemotherapy pre chemo pearson correlation 0 578 p 0 001 change chemotherapy pearson correlation 0 542 p 0 001 patients higher pre chemotherapy spd l1 1 3 ng ml showed worse os 9 2 vs 16 2 m p 0 001 spd l1 1 8 vs 1 0 ng ml p 0 001 stgf 20 5 vs 11 6 ng ml p 0 001 increased significantly time pd compared pre chemotherapy regarding changes chemotherapy increased stgf chemotherapy 3 2 ng ml worse prognosis pfs 5 1 vs 7 3 m p 0 024 os 9 2 vs 12 3 m p 0 028 prognostic value change stgf chemotherapy also significant multivariable analysis clinical factors pfs hr 1 78 p 0 022 os hr 1 86 p 0 018 conclusions btc positive association stgf spd l1 value terms baseline levels changes chemotherapy stgf associated survival particularly increased value chemotherapy indicates worse prognosis google scholar","probabilities":0.9799733,"Title":"The Prognostic Role Of Soluble Transforming Growth Factor-ß (Stgfb) And Soluble Programmed Death-Ligand 1 (Spdl1) In Biliary Tract Cancer Patients Treated With Binimetinib And Capecitabine","Abstract":"Background: We previously reported that soluble programmed death-Ligand 1 (sPD-L1) at pre-chemotherapy indicated the prognostic value for overall survival (OS) and the dynamics of sPD-L1 during palliative chemotherapy correlated with disease burden in biliary tract cancer (BTC). Transforming growth factor (TGF) -β attenuates tumor response to PD1/PD-L1 inhibitors. Strategy of dual targeting of PD1/PD-L1 and TGF-β is now under investigation. This study aimed to evaluate the association between soluble TGF-β (sTGF-β) and sPD-L1, dynamics during chemotherapy and its prognostic role in BTC. Methods: Study population consisted of 90 BTC patients treated with first line chemotherapy. Blood samples at pre-and post-chemotherapy and at disease progression (PD) were prospectively collected. Plasma sTGF-β and sPD-L1 levels were measured by using an enzyme-linked immunosorbent assay. Results: The median progression free survival (PFS) and OS of all patients was 6.9 months (m) (95% CI, 5.2-8.6) and 11.5 m (95% CI, 9.4-13.6). The best response was CR in 7 (7.8%), PR in 20 (22.2%), SD in 52 (57.8%), and PD in 11 patients (12.2%). The mean baseline sTGF-β and sPD-L1 were 16.4 ng/ml and 1.3 ng/ml. There was a positive association between sTGF-β and sPD-L1 in terms of baseline levels and changes after chemotherapy (at pre-chemo, Pearson correlation = 0.578, p < 0.001; change after chemotherapy, Pearson correlation = 0.542, p < 0.001). Patients with higher pre-chemotherapy sPD-L1 ( > 1.3 ng/ml) showed worse OS (9.2 vs 16.2 m, p < 0.001). Both sPD-L1 (1.8 vs 1.0 ng/ml, p < 0.001) and sTGF-β (20.5 vs 11.6 ng/ml, p < 0.001) were increased significantly at the time of PD compared with pre-chemotherapy. Regarding changes after chemotherapy, increased sTGF-β after chemotherapy (Δ > 3.2 ng/ml) had worse prognosis (PFS: 5.1 vs 7.3 m, p = 0.024; OS: 9.2 vs 12.3 m, p = 0.028). This prognostic value of change of sTGF-β after chemotherapy was also significant in multivariable analysis with other clinical factors (PFS: HR = 1.78, p = 0.022; OS: HR = 1.86, p = 0.018). Conclusions: In BTC, there is a positive association between sTGF-β and sPD-L1 value in terms of baseline levels and changes after chemotherapy. sTGF-β could be associated with the survival, particularly, increased value after chemotherapy indicates worse prognosis.","Source":"Google Scholar","category":"HUMAN","training_data":"The Prognostic Role Of Soluble Transforming Growth Factor-ß (Stgfb) And Soluble Programmed Death-Ligand 1 (Spdl1) In Biliary Tract Cancer Patients Treated With Binimetinib And Capecitabine Background: We previously reported that soluble programmed death-Ligand 1 (sPD-L1) at pre-chemotherapy indicated the prognostic value for overall survival (OS) and the dynamics of sPD-L1 during palliative chemotherapy correlated with disease burden in biliary tract cancer (BTC). Transforming growth factor (TGF) -β attenuates tumor response to PD1/PD-L1 inhibitors. Strategy of dual targeting of PD1/PD-L1 and TGF-β is now under investigation. This study aimed to evaluate the association between soluble TGF-β (sTGF-β) and sPD-L1, dynamics during chemotherapy and its prognostic role in BTC. Methods: Study population consisted of 90 BTC patients treated with first line chemotherapy. Blood samples at pre-and post-chemotherapy and at disease progression (PD) were prospectively collected. Plasma sTGF-β and sPD-L1 levels were measured by using an enzyme-linked immunosorbent assay. Results: The median progression free survival (PFS) and OS of all patients was 6.9 months (m) (95% CI, 5.2-8.6) and 11.5 m (95% CI, 9.4-13.6). The best response was CR in 7 (7.8%), PR in 20 (22.2%), SD in 52 (57.8%), and PD in 11 patients (12.2%). The mean baseline sTGF-β and sPD-L1 were 16.4 ng/ml and 1.3 ng/ml. There was a positive association between sTGF-β and sPD-L1 in terms of baseline levels and changes after chemotherapy (at pre-chemo, Pearson correlation = 0.578, p < 0.001; change after chemotherapy, Pearson correlation = 0.542, p < 0.001). Patients with higher pre-chemotherapy sPD-L1 ( > 1.3 ng/ml) showed worse OS (9.2 vs 16.2 m, p < 0.001). Both sPD-L1 (1.8 vs 1.0 ng/ml, p < 0.001) and sTGF-β (20.5 vs 11.6 ng/ml, p < 0.001) were increased significantly at the time of PD compared with pre-chemotherapy. Regarding changes after chemotherapy, increased sTGF-β after chemotherapy (Δ > 3.2 ng/ml) had worse prognosis (PFS: 5.1 vs 7.3 m, p = 0.024; OS: 9.2 vs 12.3 m, p = 0.028). This prognostic value of change of sTGF-β after chemotherapy was also significant in multivariable analysis with other clinical factors (PFS: HR = 1.78, p = 0.022; OS: HR = 1.86, p = 0.018). Conclusions: In BTC, there is a positive association between sTGF-β and sPD-L1 value in terms of baseline levels and changes after chemotherapy. sTGF-β could be associated with the survival, particularly, increased value after chemotherapy indicates worse prognosis. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"improvement prognosis unresectable biliary tract cancer aim evaluate chemotherapeutic outcomes confirm recent improvement prognosis unresectable biliary tract cancer methods total 186 consecutive patients unresectable biliary tract cancer treated chemotherapy 2000 2009 five institutions japan retrospectively analyzed patients divided three groups based year beginning chemotherapy group 2000 2003 group b 2004 2006 group c 2007 2009 data fixed end december 2011 overall survival time progression analyzed compared chronologically results patient characteristics significantly different among three groups gallbladder involved half patients group metastatic biliary tract cancer present three quarters enrollees group 5 fluorouracil based chemotherapies primarily selected first line chemotherapy 24 treated second line chemotherapy group b gemcitabine 1 monotherapy mainly introduced first line chemotherapy 51 patients refractory first line chemotherapy treated second line chemotherapy mainly monotherapy group c combination therapy gemcitabine 1 mainly chosen first line chemotherapy 53 patients refractory first line chemotherapy treated second line chemotherapy mainly combination therapy median time progressions 4 4 mo 3 5 mo 5 9 mo groups b c respectively 4 4 mo vs 3 5 mo vs 5 9 mo p 0 01 median overall survivals 7 1 7 3 11 7 mo groups b c 7 1 mo vs 7 3 mo vs 11 7 mo p 0 03 induction rates three drugs gemcitabine platinum analogs fluoropyrimidine groups b c 4 2 27 4 vs 2 vs 27 p 0 01 conclusion prognosis unresectable biliary tract cancer improved recently using three effective drugs gemcitabine platinum analogs fluoropyrimidine may improve prognosis cancer pubmed","probabilities":0.9799733,"Title":"Improvement of prognosis for unresectable biliary tract cancer","Abstract":"AIM: To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer. METHODS: A total of 186 consecutive patients with unresectable biliary tract cancer, who had been treated with chemotherapy between 2000 and 2009 at five institutions in Japan, were retrospectively analyzed. These patients were divided into three groups based on the year beginning chemotherapy: Group A (2000-2003), Group B (2004-2006), and Group C (2007-2009). The data were fixed at the end of December 2011. Overall survival and time-to-progression were analyzed and compared chronologically. RESULTS: No patient characteristics were significantly different among the three groups. The gallbladder was involved in about half of the patients in each group, and metastatic biliary tract cancer was present in three quarters of the enrollees. In Group A, 5-fluorouracil-based chemotherapies were primarily selected as first-line chemotherapy, and only 24% were treated with second-line chemotherapy. In Group B, gemcitabine or S-1 monotherapy was mainly introduced as first-line chemotherapy, and 51% of the patients who were refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with monotherapy. In Group C, the combination therapy with gemcitabine and S-1 was mainly chosen as first-line chemotherapy, and 53% of the patients refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with combination therapy. The median time-to-progressions were 4.4 mo, 3.5 mo and 5.9 mo in Groups A, B and C, respectively (4.4 mo vs 3.5 mo vs 5.9 mo, P < 0.01). The median overall survivals were 7.1, 7.3, and 11.7 mo in Groups A, B and C (7.1 mo vs 7.3 mo vs 11.7 mo, P = 0.03). Induction rates of all three drugs (gemcitabine, platinum analogs, and fluoropyrimidine) in Groups A, B and C were 4%, 2% and 27% (4% vs 2% vs 27%, P < 0.01). CONCLUSION: The prognosis of unresectable biliary tract cancer has improved recently. Using three effective drugs (gemcitabine, platinum analogs, and fluoropyrimidine) may improve the prognosis of this cancer.","Source":"PubMed","category":"HUMAN","training_data":"Improvement of prognosis for unresectable biliary tract cancer AIM: To evaluate the chemotherapeutic outcomes and confirm the recent improvement of prognosis for unresectable biliary tract cancer. METHODS: A total of 186 consecutive patients with unresectable biliary tract cancer, who had been treated with chemotherapy between 2000 and 2009 at five institutions in Japan, were retrospectively analyzed. These patients were divided into three groups based on the year beginning chemotherapy: Group A (2000-2003), Group B (2004-2006), and Group C (2007-2009). The data were fixed at the end of December 2011. Overall survival and time-to-progression were analyzed and compared chronologically. RESULTS: No patient characteristics were significantly different among the three groups. The gallbladder was involved in about half of the patients in each group, and metastatic biliary tract cancer was present in three quarters of the enrollees. In Group A, 5-fluorouracil-based chemotherapies were primarily selected as first-line chemotherapy, and only 24% were treated with second-line chemotherapy. In Group B, gemcitabine or S-1 monotherapy was mainly introduced as first-line chemotherapy, and 51% of the patients who were refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with monotherapy. In Group C, the combination therapy with gemcitabine and S-1 was mainly chosen as first-line chemotherapy, and 53% of the patients refractory to first-line chemotherapy were treated with second-line chemotherapy mainly with combination therapy. The median time-to-progressions were 4.4 mo, 3.5 mo and 5.9 mo in Groups A, B and C, respectively (4.4 mo vs 3.5 mo vs 5.9 mo, P < 0.01). The median overall survivals were 7.1, 7.3, and 11.7 mo in Groups A, B and C (7.1 mo vs 7.3 mo vs 11.7 mo, P = 0.03). Induction rates of all three drugs (gemcitabine, platinum analogs, and fluoropyrimidine) in Groups A, B and C were 4%, 2% and 27% (4% vs 2% vs 27%, P < 0.01). CONCLUSION: The prognosis of unresectable biliary tract cancer has improved recently. Using three effective drugs (gemcitabine, platinum analogs, and fluoropyrimidine) may improve the prognosis of this cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cyclooxygenase 2 p53 glucose transporter 1 predictors malignancy development gallbladder carcinomas gallbladder carcinoma fifth common malignancy gastrointestinal tract absolute characteristics disease high mortality rate due late discovery tumor low therapeutic possibilities except surgical intervention oncology predict outcome disease combination classical standard clinico pathological parameters stage tumors differentiation intrinsic genetic biochemical properties tumor intrinzic properties tumors connected outcome disease denominators markers author searched extensively expression influence 3 markers included chronic inflammation early carcinogenesis cell cycle regulation tissue hypoxia cyclooxygenase 2 cox 2 p53 gene glucose transporter 1 protein glut 1 author discusses possible role development well fighting disease specific medications targeting available pubmed","probabilities":0.962963,"Title":"Cyclooxygenase-2, p53 and glucose transporter-1 as predictors of malignancy in the development of gallbladder carcinomas","Abstract":"Gallbladder carcinoma is the fifth most common malignancy of the gastrointestinal tract. The absolute characteristics of the disease are the high mortality rate due to the late discovery of a tumor and the low therapeutic possibilities except by surgical intervention. In oncology we can predict the outcome of the disease with a combination of classical standard clinico/pathological parameters (stage of the tumors, differentiation) and the intrinsic genetic and biochemical properties of the tumor. Such intrinzic properties of the tumors that are connected with the outcome of the disease are the denominators (markers). The author searched extensively for the expression and influence of 3 markers included in chronic inflammation and early carcinogenesis, cell cycle regulation and tissue hypoxia: cyclooxygenase-2 (COX-2), p53 gene and glucose transporter-1 protein (GLUT-1). The author discusses their possible role in the development as well as fighting this disease, if specific medications targeting them were available.","Source":"PubMed","category":"HUMAN","training_data":"Cyclooxygenase-2, p53 and glucose transporter-1 as predictors of malignancy in the development of gallbladder carcinomas Gallbladder carcinoma is the fifth most common malignancy of the gastrointestinal tract. The absolute characteristics of the disease are the high mortality rate due to the late discovery of a tumor and the low therapeutic possibilities except by surgical intervention. In oncology we can predict the outcome of the disease with a combination of classical standard clinico/pathological parameters (stage of the tumors, differentiation) and the intrinsic genetic and biochemical properties of the tumor. Such intrinzic properties of the tumors that are connected with the outcome of the disease are the denominators (markers). The author searched extensively for the expression and influence of 3 markers included in chronic inflammation and early carcinogenesis, cell cycle regulation and tissue hypoxia: cyclooxygenase-2 (COX-2), p53 gene and glucose transporter-1 protein (GLUT-1). The author discusses their possible role in the development as well as fighting this disease, if specific medications targeting them were available. PubMed","prediction_labels":"HUMAN"},{"cleaned":"liver flukes clonorchis opisthorchis clonorchis sinensis opisthorchis viverrini o felineus liver flukes human animal pathogens occurring across much europe asia nevertheless often underestimated compared better known neglected diseases spite fact many millions people infected hundreds millions risk possibly chronic nature infection disease takes several decades prior life threatening pathology develop several studies past decade provided information molecular biology liver flukes clearly lead better understanding parasite biology systematics population genetics clonorchiasis opisthorchiasis characterized chronic infection induces hepatobiliary inflammation especially periductal fibrosis detected ultrasonography chronic inflammations eventually lead cholangiocarcinoma cca usually fatal bile duct cancer develops infected individuals thailand alone opisthorchiasis associated cca kills 20 000 people every year therefore substantial public health importance socioeconomic impacts impoverished families communities considerable reduce hepatobiliary morbidity cca primary intervention measures focus control elimination liver fluke accurate diagnosis liver fluke infections human mammalian snail fish intermediate hosts important achieving goals short term goal liver fluke control achieved praziquantel chemotherapy comprehensive health education package targeting school children believed beneficial long term goal solution recommended transdisciplinary research multisectoral control approach including one health eco health intervention strategy applied combat liver flukes hence contribute reduction cholangiocarcinoma endemic areas google scholar","probabilities":0.8684211,"Title":"Liver Flukes: Clonorchis And Opisthorchis","Abstract":"Clonorchis sinensis, Opisthorchis viverrini, and O. felineus are liver flukes of human and animal pathogens occurring across much of Europe and Asia. Nevertheless, they are often underestimated compared to other, better known neglected diseases in spite of the fact that many millions of people are infected and hundreds of millions are at risk. This is possibly because of the chronic nature of the infection and disease and that it takes several decades prior to a life-threatening pathology to develop. Several studies in the past decade have provided more information on the molecular biology of the liver flukes which clearly lead to better understanding of parasite biology, systematics, and population genetics. Clonorchiasis and opisthorchiasis are characterized by a chronic infection that induces hepatobiliary inflammation, especially periductal fibrosis, which can be detected by ultrasonography. These chronic inflammations eventually lead to cholangiocarcinoma (CCA), a usually fatal bile duct cancer that develops in some infected individuals. In Thailand alone, opisthorchiasis-associated CCA kills up to 20,000 people every year and is therefore of substantial public health importance. Its socioeconomic impacts on impoverished families and communities are considerable. To reduce hepatobiliary morbidity and CCA, the primary intervention measures focus on control and elimination of the liver fluke. Accurate diagnosis of liver fluke infections in both human and other mammalian, snail and fish intermediate hosts, are important for achieving these goals. While the short-term goal of liver fluke control can be achieved by praziquantel chemotherapy, a comprehensive health education package targeting school children is believed to be more beneficial for a long-term goal/solution. It is recommended that a transdisciplinary research or multisectoral control approach including one health and/or eco health intervention strategy should be applied to combat the liver flukes, and hence contribute to reduction of cholangiocarcinoma in endemic areas.","Source":"Google Scholar","category":"HUMAN","training_data":"Liver Flukes: Clonorchis And Opisthorchis Clonorchis sinensis, Opisthorchis viverrini, and O. felineus are liver flukes of human and animal pathogens occurring across much of Europe and Asia. Nevertheless, they are often underestimated compared to other, better known neglected diseases in spite of the fact that many millions of people are infected and hundreds of millions are at risk. This is possibly because of the chronic nature of the infection and disease and that it takes several decades prior to a life-threatening pathology to develop. Several studies in the past decade have provided more information on the molecular biology of the liver flukes which clearly lead to better understanding of parasite biology, systematics, and population genetics. Clonorchiasis and opisthorchiasis are characterized by a chronic infection that induces hepatobiliary inflammation, especially periductal fibrosis, which can be detected by ultrasonography. These chronic inflammations eventually lead to cholangiocarcinoma (CCA), a usually fatal bile duct cancer that develops in some infected individuals. In Thailand alone, opisthorchiasis-associated CCA kills up to 20,000 people every year and is therefore of substantial public health importance. Its socioeconomic impacts on impoverished families and communities are considerable. To reduce hepatobiliary morbidity and CCA, the primary intervention measures focus on control and elimination of the liver fluke. Accurate diagnosis of liver fluke infections in both human and other mammalian, snail and fish intermediate hosts, are important for achieving these goals. While the short-term goal of liver fluke control can be achieved by praziquantel chemotherapy, a comprehensive health education package targeting school children is believed to be more beneficial for a long-term goal/solution. It is recommended that a transdisciplinary research or multisectoral control approach including one health and/or eco health intervention strategy should be applied to combat the liver flukes, and hence contribute to reduction of cholangiocarcinoma in endemic areas. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"isolation cancer associated fibroblasts promotion progression intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma highly fatal tumor characterized abundant stromal environment cancer associated fibroblasts play key roles tumor growth invasiveness regarded potential therapeutic target study designed isolate human primary cancer associated fibroblasts intrahepatic cholangiocarcinoma study tumor stroma interactions analyze clinical relevance alpha smooth muscle actin positive cancer associated fibroblasts patients intrahepatic cholangiocarcinoma isolated cancer associated fibroblasts positive alpha smooth actin fibroblast specific protein 1 fibroblast activation protein pdgfr addition cancer associated fibroblasts found increase proliferation migration invasion cholangiocarcinoma cells vitro promote tumor growth mice vivo moreover alpha smooth muscle actin positive expression cancer associated fibroblasts predicted unfavorable prognosis patients intrahepatic cholangiocarcinoma showed correlation presence lymph node metastasis study may provide useful tool investigate effect cancer associated fibroblasts molecular mechanism cholangiocarcinoma cells well contribution cancer associated fibroblasts lymphangiogenesis lymph node metastasis stn","probabilities":1.0,"Title":"Isolation Of Cancer-Associated Fibroblasts And Its Promotion To The Progression Of Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma is a highly fatal tumor characterized by an abundant stromal environment. Cancer-associated fibroblasts play key roles in tumor growth and invasiveness and have been regarded as a potential therapeutic target. This study was designed to isolate human primary cancer-associated fibroblasts of intrahepatic cholangiocarcinoma to study tumor-stroma interactions and to analyze the clinical relevance of alpha-smooth muscle actin -positive cancer-associated fibroblasts in patients with intrahepatic cholangiocarcinoma. The isolated cancer-associated fibroblasts were positive for alpha-smooth actin, fibroblast-specific protein-1, fibroblast activation protein, and PDGFR-β. In addition, cancer-associated fibroblasts were found to increase proliferation, migration, and invasion of cholangiocarcinoma cells in vitro and promote tumor growth of mice in vivo. Moreover, alpha-smooth muscle actin-positive expression of cancer-associated fibroblasts predicted unfavorable prognosis in patients with intrahepatic cholangiocarcinoma and showed correlation with presence of lymph node metastasis. This study may provide a useful tool to investigate further effect of cancer-associated fibroblasts on the molecular mechanism of cholangiocarcinoma cells as well as contribution of cancer-associated fibroblasts in lymphangiogenesis and lymph node metastasis.","Source":"STN","category":"ANIMAL","training_data":"Isolation Of Cancer-Associated Fibroblasts And Its Promotion To The Progression Of Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma is a highly fatal tumor characterized by an abundant stromal environment. Cancer-associated fibroblasts play key roles in tumor growth and invasiveness and have been regarded as a potential therapeutic target. This study was designed to isolate human primary cancer-associated fibroblasts of intrahepatic cholangiocarcinoma to study tumor-stroma interactions and to analyze the clinical relevance of alpha-smooth muscle actin -positive cancer-associated fibroblasts in patients with intrahepatic cholangiocarcinoma. The isolated cancer-associated fibroblasts were positive for alpha-smooth actin, fibroblast-specific protein-1, fibroblast activation protein, and PDGFR-β. In addition, cancer-associated fibroblasts were found to increase proliferation, migration, and invasion of cholangiocarcinoma cells in vitro and promote tumor growth of mice in vivo. Moreover, alpha-smooth muscle actin-positive expression of cancer-associated fibroblasts predicted unfavorable prognosis in patients with intrahepatic cholangiocarcinoma and showed correlation with presence of lymph node metastasis. This study may provide a useful tool to investigate further effect of cancer-associated fibroblasts on the molecular mechanism of cholangiocarcinoma cells as well as contribution of cancer-associated fibroblasts in lymphangiogenesis and lymph node metastasis. STN","prediction_labels":"ANIMAL"},{"cleaned":"whole genome epigenomic landscapes etiologically distinct subtypes cholangiocarcinoma cholangiocarcinoma cca hepatobiliary malignancy exhibiting high incidence countries endemic liver fluke infection analyzed 489 ccas 10 countries combining whole genome 71 cases targeted exome copy number gene expression dna methylation information integrative clustering defined 4 cca clusters fluke positive ccas clusters 1 2 enriched erbb2 amplifications tp53 mutations conversely fluke negative ccas clusters 3 4 exhibit high copy number alterations pd 1 pd l2 expression epigenetic mutations idh1 2 bap1 fgfr prka related gene rearrangements whole genome analysis highlighted fgfr2 3 untranslated region deletion mechanism fgfr2 upregulation integration noncoding promoter mutations protein dna binding profiles demonstrates pervasive modulation h3k27me3 associated sites cca clusters 1 4 exhibit distinct dna hypermethylation patterns targeting either cpg islands shores mutation signature subclonality analysis suggests reflect different mutational pathways results exemplify genetics epigenetics environmental carcinogens interplay across different geographies generate distinct molecular subtypes cancer significance integrated whole genome epigenomic analysis cca international scale identifies new cca driver genes noncoding promoter mutations structural variants cca molecular landscapes differ radically etiology underscoring distinct cancer subtypes organ may arise different extrinsic intrinsic carcinogenic processes cancer discov 7 10 1116 35 2017 aacr article highlighted issue feature p 1047 stn","probabilities":0.9799733,"Title":"Whole-Genome And Epigenomic Landscapes Of Etiologically Distinct Subtypes Of Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3' untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores-mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.Significance: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes. Cancer Discov; 7(10); 1116-35. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1047.","Source":"STN","category":"ANIMAL","training_data":"Whole-Genome And Epigenomic Landscapes Of Etiologically Distinct Subtypes Of Cholangiocarcinoma Cholangiocarcinoma (CCA) is a hepatobiliary malignancy exhibiting high incidence in countries with endemic liver-fluke infection. We analyzed 489 CCAs from 10 countries, combining whole-genome (71 cases), targeted/exome, copy-number, gene expression, and DNA methylation information. Integrative clustering defined 4 CCA clusters-fluke-positive CCAs (clusters 1/2) are enriched in ERBB2 amplifications and TP53 mutations; conversely, fluke-negative CCAs (clusters 3/4) exhibit high copy-number alterations and PD-1/PD-L2 expression, or epigenetic mutations (IDH1/2, BAP1) and FGFR/PRKA-related gene rearrangements. Whole-genome analysis highlighted FGFR2 3' untranslated region deletion as a mechanism of FGFR2 upregulation. Integration of noncoding promoter mutations with protein-DNA binding profiles demonstrates pervasive modulation of H3K27me3-associated sites in CCA. Clusters 1 and 4 exhibit distinct DNA hypermethylation patterns targeting either CpG islands or shores-mutation signature and subclonality analysis suggests that these reflect different mutational pathways. Our results exemplify how genetics, epigenetics, and environmental carcinogens can interplay across different geographies to generate distinct molecular subtypes of cancer.Significance: Integrated whole-genome and epigenomic analysis of CCA on an international scale identifies new CCA driver genes, noncoding promoter mutations, and structural variants. CCA molecular landscapes differ radically by etiology, underscoring how distinct cancer subtypes in the same organ may arise through different extrinsic and intrinsic carcinogenic processes. Cancer Discov; 7(10); 1116-35. ©2017 AACR.This article is highlighted in the In This Issue feature, p. 1047. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance immune cells tumor microenvironment peripheral blood gallbladder carcinoma patients background role interaction tumor cells inflammatory cells gallbladder carcinoma gbc unclear inflammatory cells exist tumor immune microenvironment host peripheral blood circulatory system current study examined prognostic value inflammatory cells tumor microenvironment peripheral blood patients gbc methods 98 patients gbc recruited retrospective study using immunohistochemistry examined tumor infiltrating cd3 generic cells cd8 cytotoxic cells cd45ro memory cells cd15 neutrophils peripheral venous blood samples also collected absolute neutrophil count anc absolute lymphocyte count alc neutrophil lymphocyte ratio nlr measured relationships variables patient outcome evaluated results survival analysis revealed density cd3 cell infiltrates tumor microenvironment positively correlated overall survival os density cd15 cell infiltrates negatively correlated os combined analysis showed high density cd3 cell infiltrates combined low density cd15 cell infiltrates independent prognostic factor gbc peripheral blood survival analysis suggested anc nlr negatively correlated alc positively correlated os multivariate survival analysis showed nlr independent prognostic factor gallbladder cancer prognosis conclusions results indicate combination high density cd3 cell infiltrates combined low density cd15 cell infiltrates tumor samples pretreatment peripheral blood nlr independent prognostic factors patients gbc pubmed","probabilities":0.962963,"Title":"Prognostic significance of immune cells in the tumor microenvironment and peripheral blood of gallbladder carcinoma patients","Abstract":"BACKGROUND: The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC. METHODS: 98 patients with GBC were recruited in this retrospective study. Using immunohistochemistry, we examined tumor-infiltrating CD3+ generic T-cells, CD8+ cytotoxic T-cells, CD45RO+ memory T-cells, and CD15+ neutrophils. Peripheral venous blood samples were also collected, and absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) were measured. The relationships between these variables and patient outcome were evaluated. RESULTS: Survival analysis revealed that the density of CD3+ cell infiltrates in the tumor microenvironment was positively correlated with overall survival (OS) and the density of CD15+ cell infiltrates was negatively correlated with the OS. The combined analysis showed that a high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates was an independent prognostic factor for GBC. In peripheral blood, survival analysis suggested that ANC and NLR were negatively correlated, while ALC was positively correlated with OS. Multivariate survival analysis showed that NLR was an independent prognostic factor for gallbladder cancer prognosis. CONCLUSIONS: The results indicate that the combination of high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates in tumor samples and pretreatment peripheral blood NLR were independent prognostic factors in patients with GBC.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of immune cells in the tumor microenvironment and peripheral blood of gallbladder carcinoma patients BACKGROUND: The role of the interaction between tumor cells and inflammatory cells in gallbladder carcinoma (GBC) is unclear. Inflammatory cells exist in both the tumor immune microenvironment and the host peripheral blood circulatory system. In the current study, we examined the prognostic value of inflammatory cells in the tumor microenvironment and peripheral blood in patients with GBC. METHODS: 98 patients with GBC were recruited in this retrospective study. Using immunohistochemistry, we examined tumor-infiltrating CD3+ generic T-cells, CD8+ cytotoxic T-cells, CD45RO+ memory T-cells, and CD15+ neutrophils. Peripheral venous blood samples were also collected, and absolute neutrophil count (ANC), absolute lymphocyte count (ALC) and neutrophil/lymphocyte ratio (NLR) were measured. The relationships between these variables and patient outcome were evaluated. RESULTS: Survival analysis revealed that the density of CD3+ cell infiltrates in the tumor microenvironment was positively correlated with overall survival (OS) and the density of CD15+ cell infiltrates was negatively correlated with the OS. The combined analysis showed that a high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates was an independent prognostic factor for GBC. In peripheral blood, survival analysis suggested that ANC and NLR were negatively correlated, while ALC was positively correlated with OS. Multivariate survival analysis showed that NLR was an independent prognostic factor for gallbladder cancer prognosis. CONCLUSIONS: The results indicate that the combination of high density of CD3+ cell infiltrates combined with a low density of CD15+ cell infiltrates in tumor samples and pretreatment peripheral blood NLR were independent prognostic factors in patients with GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"molecular pathogenesis cholangiocarcinoma background cholangiocarcinomas heterogeneous group malignancies arising number cells origin along biliary tree although cases western countries sporadic large population based studies identified number risk factors review summarises evidence behind reported risk factors current understanding molecular pathogenesis cholangiocarcinoma focus inflammation cholestasis driving forces cholangiocarcinoma development risk factors cholangiocarcinogenesis cholestatic liver diseases e g primary sclerosing cholangitis fibropolycystic liver diseases liver cirrhosis biliary stone disease increase risk cholangiocarcinoma certain bacterial viral parasitic infections hepatitis b c liver flukes also increase cholangiocarcinoma risk risk factors include inflammatory disorders inflammatory bowel disease chronic pancreatitis toxins e g alcohol tobacco metabolic conditions diabetes obesity non alcoholic fatty liver disease number genetic disorders molecular pathogenesis cholangiocarcinoma regardless aetiology risk factors cause chronic inflammation cholestasis chronic inflammation leads increased exposure cholangiocytes inflammatory mediators interleukin 6 tumour necrosis factor cyclo oxygenase 2 wnt resulting progressive mutations tumour suppressor genes proto oncogenes dna mismatch repair genes accumulating bile acids cholestasis lead reduced ph increased apoptosis activation erk1 2 akt nf b pathways encourage cell proliferation migration survival mediators upregulated cholangiocarcinoma include transforming growth factor vascular endothelial growth factor hepatocyte growth factor several micrornas increased expression cell surface receptor c met glucose transporter glut 1 sodium iodide symporter lead tumour growth angiogenesis cell migration stromal changes also observed resulting alterations extracellular matrix composition recruitment fibroblasts macrophages create microenvironment promoting cell survival invasion metastasis conclusion regardless aetiology risk factors cholangiocarcinoma cause chronic inflammation cholestasis leading activation common intracellular pathways result reactive cell proliferation genetic epigenetic mutations cholangiocarcinogenesis understanding molecular pathogenesis cholangiocarcinoma vital developing new diagnostic biomarkers targeted therapies disease pubmed","probabilities":0.962963,"Title":"Molecular Pathogenesis of Cholangiocarcinoma","Abstract":"BACKGROUND: Cholangiocarcinomas are a heterogeneous group of malignancies arising from a number of cells of origin along the biliary tree. Although most cases in Western countries are sporadic, large population-based studies have identified a number of risk factors. This review summarises the evidence behind reported risk factors and current understanding of the molecular pathogenesis of cholangiocarcinoma, with a focus on inflammation and cholestasis as the driving forces in cholangiocarcinoma development. RISK FACTORS FOR CHOLANGIOCARCINOGENESIS: Cholestatic liver diseases (e.g. primary sclerosing cholangitis and fibropolycystic liver diseases), liver cirrhosis, and biliary stone disease all increase the risk of cholangiocarcinoma. Certain bacterial, viral or parasitic infections such as hepatitis B and C and liver flukes also increase cholangiocarcinoma risk. Other risk factors include inflammatory disorders (such as inflammatory bowel disease and chronic pancreatitis), toxins (e.g. alcohol and tobacco), metabolic conditions (diabetes, obesity and non-alcoholic fatty liver disease) and a number of genetic disorders. MOLECULAR PATHOGENESIS OF CHOLANGIOCARCINOMA: Regardless of aetiology, most risk factors cause chronic inflammation or cholestasis. Chronic inflammation leads to increased exposure of cholangiocytes to the inflammatory mediators interleukin-6, Tumour Necrosis Factor-ɑ, Cyclo-oxygenase-2 and Wnt, resulting in progressive mutations in tumour suppressor genes, proto-oncogenes and DNA mismatch-repair genes. Accumulating bile acids from cholestasis lead to reduced pH, increased apoptosis and activation of ERK1/2, Akt and NF-κB pathways that encourage cell proliferation, migration and survival. Other mediators upregulated in cholangiocarcinoma include Transforming Growth Factor-β, Vascular Endothelial Growth Factor, Hepatocyte Growth Factor and several microRNAs. Increased expression of the cell surface receptor c-Met, the glucose transporter GLUT-1 and the sodium iodide symporter lead to tumour growth, angiogenesis and cell migration. Stromal changes are also observed, resulting in alterations to the extracellular matrix composition and recruitment of fibroblasts and macrophages that create a microenvironment promoting cell survival, invasion and metastasis. CONCLUSION: Regardless of aetiology, most risk factors for cholangiocarcinoma cause chronic inflammation and/or cholestasis, leading to the activation of common intracellular pathways that result in reactive cell proliferation, genetic/epigenetic mutations and cholangiocarcinogenesis. An understanding of the molecular pathogenesis of cholangiocarcinoma is vital when developing new diagnostic biomarkers and targeted therapies for this disease.","Source":"PubMed","category":"HUMAN","training_data":"Molecular Pathogenesis of Cholangiocarcinoma BACKGROUND: Cholangiocarcinomas are a heterogeneous group of malignancies arising from a number of cells of origin along the biliary tree. Although most cases in Western countries are sporadic, large population-based studies have identified a number of risk factors. This review summarises the evidence behind reported risk factors and current understanding of the molecular pathogenesis of cholangiocarcinoma, with a focus on inflammation and cholestasis as the driving forces in cholangiocarcinoma development. RISK FACTORS FOR CHOLANGIOCARCINOGENESIS: Cholestatic liver diseases (e.g. primary sclerosing cholangitis and fibropolycystic liver diseases), liver cirrhosis, and biliary stone disease all increase the risk of cholangiocarcinoma. Certain bacterial, viral or parasitic infections such as hepatitis B and C and liver flukes also increase cholangiocarcinoma risk. Other risk factors include inflammatory disorders (such as inflammatory bowel disease and chronic pancreatitis), toxins (e.g. alcohol and tobacco), metabolic conditions (diabetes, obesity and non-alcoholic fatty liver disease) and a number of genetic disorders. MOLECULAR PATHOGENESIS OF CHOLANGIOCARCINOMA: Regardless of aetiology, most risk factors cause chronic inflammation or cholestasis. Chronic inflammation leads to increased exposure of cholangiocytes to the inflammatory mediators interleukin-6, Tumour Necrosis Factor-ɑ, Cyclo-oxygenase-2 and Wnt, resulting in progressive mutations in tumour suppressor genes, proto-oncogenes and DNA mismatch-repair genes. Accumulating bile acids from cholestasis lead to reduced pH, increased apoptosis and activation of ERK1/2, Akt and NF-κB pathways that encourage cell proliferation, migration and survival. Other mediators upregulated in cholangiocarcinoma include Transforming Growth Factor-β, Vascular Endothelial Growth Factor, Hepatocyte Growth Factor and several microRNAs. Increased expression of the cell surface receptor c-Met, the glucose transporter GLUT-1 and the sodium iodide symporter lead to tumour growth, angiogenesis and cell migration. Stromal changes are also observed, resulting in alterations to the extracellular matrix composition and recruitment of fibroblasts and macrophages that create a microenvironment promoting cell survival, invasion and metastasis. CONCLUSION: Regardless of aetiology, most risk factors for cholangiocarcinoma cause chronic inflammation and/or cholestasis, leading to the activation of common intracellular pathways that result in reactive cell proliferation, genetic/epigenetic mutations and cholangiocarcinogenesis. An understanding of the molecular pathogenesis of cholangiocarcinoma is vital when developing new diagnostic biomarkers and targeted therapies for this disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"defining role adjuvant therapy ampullary duodenal adenocarcinoma adenocarcinomas ampulla vater duodenum rare pancreatic cancer better prognosis however studies conducted management cancers adjuvant chemotherapy radiation therapy limited small sample sizes series retrospective review evaluates ampullary duodenal adenocarcinomas regard incidence anatomy prognostic features patterns failure available literature studying adjuvant therapy pubmed","probabilities":0.9799733,"Title":"Defining the role of adjuvant therapy: ampullary and duodenal adenocarcinoma","Abstract":"Adenocarcinomas of the ampulla of Vater and duodenum are more rare than pancreatic cancer and have a better prognosis. However, studies conducted on the management of these cancers, such as adjuvant chemotherapy and radiation therapy, are limited by small sample sizes and series that are retrospective. This review evaluates ampullary and duodenal adenocarcinomas with regard to incidence, anatomy, prognostic features, patterns of failure, and the available literature studying adjuvant therapy.","Source":"PubMed","category":"HUMAN","training_data":"Defining the role of adjuvant therapy: ampullary and duodenal adenocarcinoma Adenocarcinomas of the ampulla of Vater and duodenum are more rare than pancreatic cancer and have a better prognosis. However, studies conducted on the management of these cancers, such as adjuvant chemotherapy and radiation therapy, are limited by small sample sizes and series that are retrospective. This review evaluates ampullary and duodenal adenocarcinomas with regard to incidence, anatomy, prognostic features, patterns of failure, and the available literature studying adjuvant therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"lymph node micrometastasis gallbladder cancer background prognosis gallbladder cancer gbc grim even curative surgery lymph node metastasis important prognostic factor distant relapses occurring absence point towards additional factor lymph node micrometastasis one present study aimed evaluate incidence clinical significance lymph node micrometastasis methods prospective study patients undergoing curative surgery gbc 1 march 2013 30 april 2015 institute lymph nodes examined hematoxylin eosin immunohistochemistry ck7 incidence lymph node relation clinicopathological parameters recurrence survival evaluated results 589 lymph nodes retrieved 40 patients metastasis seen 13 2 20 nodes 8 20 patients micrometastasis 4 0 68 nodes 3 7 5 patients micrometastases absent pt1 tumors 0 10 pt1 vs 3 30 pt2 4 common patients nodal metastasis 13 vs 6 though presence micrometastasis upstaged disease statistically relate clinicopathological parameters recurrence survival conclusions incidence lymph node micrometastasis gbc low correlate clinicopathological parameters recurrence survival pubmed","probabilities":0.9799733,"Title":"Lymph node micrometastasis in gallbladder cancer","Abstract":"BACKGROUND: Prognosis of gallbladder cancer (GBC) is grim even after curative surgery. Lymph node metastasis is the most important prognostic factor, but distant relapses occurring in their absence point towards additional factor. Lymph node micrometastasis could be one. The present study aimed to evaluate the incidence and clinical significance of lymph node micrometastasis. METHODS: This is a prospective study of patients undergoing curative surgery for GBC from 1 March 2013 to 30 April 2015, at our institute. All lymph nodes were examined with hematoxylin and eosin and immunohistochemistry against CK7. The incidence of lymph node and its relation to other clinicopathological parameters, recurrence, and survival was evaluated. RESULTS: Out of 589 lymph nodes retrieved from 40 patients, metastasis was seen in 13 (2.20%) nodes from 8 (20%) patients and micrometastasis in 4 (0.68%) nodes from 3 (7.5%) patients. Micrometastases were absent in pT1 tumors (0/10 in pT1 vs. 3/30 in pT2-4) and more common in patients with nodal metastasis (13% vs. 6%). Though the presence of micrometastasis would have upstaged the disease, it did not statistically relate to clinicopathological parameters, recurrence, and survival. CONCLUSIONS: Incidence of lymph node micrometastasis in GBC was low and did not correlate with other clinicopathological parameters, recurrence, and survival.","Source":"PubMed","category":"HUMAN","training_data":"Lymph node micrometastasis in gallbladder cancer BACKGROUND: Prognosis of gallbladder cancer (GBC) is grim even after curative surgery. Lymph node metastasis is the most important prognostic factor, but distant relapses occurring in their absence point towards additional factor. Lymph node micrometastasis could be one. The present study aimed to evaluate the incidence and clinical significance of lymph node micrometastasis. METHODS: This is a prospective study of patients undergoing curative surgery for GBC from 1 March 2013 to 30 April 2015, at our institute. All lymph nodes were examined with hematoxylin and eosin and immunohistochemistry against CK7. The incidence of lymph node and its relation to other clinicopathological parameters, recurrence, and survival was evaluated. RESULTS: Out of 589 lymph nodes retrieved from 40 patients, metastasis was seen in 13 (2.20%) nodes from 8 (20%) patients and micrometastasis in 4 (0.68%) nodes from 3 (7.5%) patients. Micrometastases were absent in pT1 tumors (0/10 in pT1 vs. 3/30 in pT2-4) and more common in patients with nodal metastasis (13% vs. 6%). Though the presence of micrometastasis would have upstaged the disease, it did not statistically relate to clinicopathological parameters, recurrence, and survival. CONCLUSIONS: Incidence of lymph node micrometastasis in GBC was low and did not correlate with other clinicopathological parameters, recurrence, and survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance telomerase activity human telomerase reverse transcriptase expression ampullary carcinoma background telomerase activity human telomerase reverse transcriptase tert reported markers tumor aggressiveness poor prognosis several digestive cancers present study examined telomerase activity tert expression ampullary carcinoma determine whether parameters used indicators aggressiveness prognosis methods telomerase activity analyzed using telomeric repeat amplification protocol assay tert examined immunohistochemistry ampullary carcinoma tissue samples resected 46 patients results telomerase activity detected 42 91 3 ampullary carcinomas 27 58 7 showed high activity whereas tert expression detected 35 76 1 including 21 weak expression 14 strong expression univariate analysis revealed histological grade p 0 029 tumor depth p 0 001 nodal status p 0 013 uicc stage p 0 009 perineural invasion p 0 001 telomerase activity p 0 031 significantly associated disease specific survival multivariate analysis telomerase activity remained independent predictor prognosis p 0 043 statistical significance survival among three grades tert expression p 0 054 however subgroup analysis patients strong tert expression showed significantly poorer prognosis without tert expression p 0 013 conclusions results suggest high telomerase activity strong tert expression may serve new prognostic markers evaluating prognosis patients resected ampullary carcinoma pubmed","probabilities":0.8684211,"Title":"Prognostic significance of telomerase activity and human telomerase reverse transcriptase expression in ampullary carcinoma","Abstract":"BACKGROUND: Telomerase activity and human telomerase reverse transcriptase (TERT) have been reported as markers of tumor aggressiveness and poor prognosis in several digestive cancers. In the present study, we examined telomerase activity and TERT expression in ampullary carcinoma to determine whether these parameters could be used as indicators of aggressiveness and prognosis. METHODS: Telomerase activity was analyzed by using the telomeric repeat amplification protocol assay, and TERT was examined by immunohistochemistry in ampullary carcinoma tissue samples resected from 46 patients. RESULTS: Telomerase activity was detected in 42 (91.3%) ampullary carcinomas and 27 (58.7%) showed high activity, whereas TERT expression was detected in 35 (76.1%), including 21 with weak expression and 14 with strong expression. Univariate analysis revealed that histological grade (P = 0.029), tumor depth (P < 0.001), nodal status (P = 0.013), UICC stage (P = 0.009), perineural invasion (P < 0.001), and telomerase activity (P = 0.031) were significantly associated with disease-specific survival. In multivariate analysis, only telomerase activity remained an independent predictor of prognosis (P = 0.043). There was no statistical significance for survival among the three grades of TERT expression (P = 0.054); however, in subgroup analysis, patients with strong TERT expression showed significantly poorer prognosis than those without TERT expression (P = 0.013). CONCLUSIONS: Our results suggest that high telomerase activity and strong TERT expression may serve as new prognostic markers for evaluating the prognosis of patients with resected ampullary carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of telomerase activity and human telomerase reverse transcriptase expression in ampullary carcinoma BACKGROUND: Telomerase activity and human telomerase reverse transcriptase (TERT) have been reported as markers of tumor aggressiveness and poor prognosis in several digestive cancers. In the present study, we examined telomerase activity and TERT expression in ampullary carcinoma to determine whether these parameters could be used as indicators of aggressiveness and prognosis. METHODS: Telomerase activity was analyzed by using the telomeric repeat amplification protocol assay, and TERT was examined by immunohistochemistry in ampullary carcinoma tissue samples resected from 46 patients. RESULTS: Telomerase activity was detected in 42 (91.3%) ampullary carcinomas and 27 (58.7%) showed high activity, whereas TERT expression was detected in 35 (76.1%), including 21 with weak expression and 14 with strong expression. Univariate analysis revealed that histological grade (P = 0.029), tumor depth (P < 0.001), nodal status (P = 0.013), UICC stage (P = 0.009), perineural invasion (P < 0.001), and telomerase activity (P = 0.031) were significantly associated with disease-specific survival. In multivariate analysis, only telomerase activity remained an independent predictor of prognosis (P = 0.043). There was no statistical significance for survival among the three grades of TERT expression (P = 0.054); however, in subgroup analysis, patients with strong TERT expression showed significantly poorer prognosis than those without TERT expression (P = 0.013). CONCLUSIONS: Our results suggest that high telomerase activity and strong TERT expression may serve as new prognostic markers for evaluating the prognosis of patients with resected ampullary carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumor associated lymphangiogenesis predicts unfavorable prognosis intrahepatic cholangiocarcinoma background tumor associated lymphangiogenesis considered significant number solid malignancies however impact prognosis intrahepatic cholangiocarcinoma icc resection remains confirmation herein conducted study evaluate prognostic impact tumor associated lymphangiogenesis patients icc methods extent tumor associated lymphangiogenesis icc evaluated quantifying microlymphatic vessel density mlvd immunohistochemical staining lymphatic endothelial specific antibody podoplanin clinicopathological characteristics comprehensively analyzed identify mlvd associated factors patients stratified high low mlvd groups according distinctive correlation mlvd overall survival using spearman correlation test kaplan meier estimation performed confirm prognostic impact mlvd patients icc univariate multivariate analyses performed using cox proportional hazard model results mlvd 4 12 counts showed inverse proportion overall survival spearman r 0 66 95 confidence interval ci 0 82 0 39 p 0 0001 set cut high mlvd group whereas mlvd 13 25 showed correlation overall survival r 0 11 95 ci 0 38 0 19 p 0 4791 high mlvd group showed frequent lymph node metastasis p 0 001 likely suffer recurrence tumor compared low mlvd group p 0 001 high mlvd found independently associated reduced overall recurrence free survival 5 year overall survival patients high mlvd significantly lower compared low mlvd 0 vs 48 conclusions study reveals tumor associated lymphangiogenesis significantly associated increased lymphatic metastasis recurrence tumor reduced overall survival patients icc thus providing guidance estimating postresection prognosis pubmed","probabilities":0.9799733,"Title":"Tumor-associated lymphangiogenesis predicts unfavorable prognosis of intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Tumor-associated lymphangiogenesis is considered significant in number of solid malignancies. However, its impact on prognosis of intrahepatic cholangiocarcinoma (ICC) after resection remains further confirmation. Herein, we conducted this study to evaluate prognostic impact of tumor-associated lymphangiogenesis in patients with ICC. METHODS: Extent of tumor-associated lymphangiogenesis of ICC was evaluated by quantifying microlymphatic vessel density (MLVD) from immunohistochemical staining of a lymphatic endothelial-specific antibody (podoplanin). Clinicopathological characteristics were comprehensively analyzed to identify MLVD-associated factors. The patients were stratified into high and low MLVD groups according to the distinctive correlation between the MLVD and overall survival using the Spearman's correlation test. Kaplan-Meier estimation was performed to confirm prognostic impact of MLVD in patients with ICC. Univariate and multivariate analyses were performed using the Cox proportional hazard model. RESULTS: The MLVD between 4 to 12 counts showed inverse proportion to the overall survival (Spearman's r = - 0.66; 95% confidence interval [CI], - 0.82 to - 0.39; p <  0.0001), which was set as a cut-off for the high MLVD group, whereas the MLVD between 13 to 25 showed no correlation to the overall survival (r = - 0.11; 95% CI, - 0.38 to 0.19; p = 0.4791). The high MLVD group showed more frequent lymph node metastasis (p <  0.001) and were more likely to suffer from recurrence of the tumor compared to the low MLVD group (p <  0.001). The high MLVD was found to be independently associated with reduced overall and recurrence-free survival. The 5-year overall survival of the patients with high MLVD was significantly lower compared to those with low MLVD (0% vs 48%). CONCLUSIONS: Our study reveals that tumor-associated lymphangiogenesis is significantly associated with increased lymphatic metastasis, recurrence of the tumor, and reduced overall survival in patients with ICC, thus providing guidance when estimating postresection prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Tumor-associated lymphangiogenesis predicts unfavorable prognosis of intrahepatic cholangiocarcinoma BACKGROUND: Tumor-associated lymphangiogenesis is considered significant in number of solid malignancies. However, its impact on prognosis of intrahepatic cholangiocarcinoma (ICC) after resection remains further confirmation. Herein, we conducted this study to evaluate prognostic impact of tumor-associated lymphangiogenesis in patients with ICC. METHODS: Extent of tumor-associated lymphangiogenesis of ICC was evaluated by quantifying microlymphatic vessel density (MLVD) from immunohistochemical staining of a lymphatic endothelial-specific antibody (podoplanin). Clinicopathological characteristics were comprehensively analyzed to identify MLVD-associated factors. The patients were stratified into high and low MLVD groups according to the distinctive correlation between the MLVD and overall survival using the Spearman's correlation test. Kaplan-Meier estimation was performed to confirm prognostic impact of MLVD in patients with ICC. Univariate and multivariate analyses were performed using the Cox proportional hazard model. RESULTS: The MLVD between 4 to 12 counts showed inverse proportion to the overall survival (Spearman's r = - 0.66; 95% confidence interval [CI], - 0.82 to - 0.39; p <  0.0001), which was set as a cut-off for the high MLVD group, whereas the MLVD between 13 to 25 showed no correlation to the overall survival (r = - 0.11; 95% CI, - 0.38 to 0.19; p = 0.4791). The high MLVD group showed more frequent lymph node metastasis (p <  0.001) and were more likely to suffer from recurrence of the tumor compared to the low MLVD group (p <  0.001). The high MLVD was found to be independently associated with reduced overall and recurrence-free survival. The 5-year overall survival of the patients with high MLVD was significantly lower compared to those with low MLVD (0% vs 48%). CONCLUSIONS: Our study reveals that tumor-associated lymphangiogenesis is significantly associated with increased lymphatic metastasis, recurrence of the tumor, and reduced overall survival in patients with ICC, thus providing guidance when estimating postresection prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact positive lymph nodes stages t1 t3 incidental gallbladder carcinoma results german registry background literature 5 year survival rates incidental gallbladder carcinoma igbc show large variations different stages lymph node status often addressed early stage carcinomas identified laparoscopy igbc radical re resection needed staging impossible without lymph node dissection comparison various survival rates impossible study aimed determine influence lymph node status survival patients stages t1 t3 igbc methods data analysis german registry used results study 709 patients igbc analyzed re resected nodal negative patients significant survival advantage re resected nodal positive patients 5 year survival rate patients nodal negative re resected t1 carcinomas 75 re resected t2 t3 nodal negative patients significantly better survival corresponding nodal positive patients influence radicalness different liver resection techniques results excluded 53 patients without radical resection known nodal positive status nodal positive patients radical re resection always show better survival rate nodal positive patients without radical re resection stage stage conclusions nodal positive status significant negative prognostic factor t1 t3 igbc patients radical re resection show better survival rate without lymph node dissection highly recommended stage t1b case t2 carcinomas lymph node dissection hepatoduodenal ligament seems minimum volume lymph node dissection required radical procedures beneficial tumors infiltrating serosa beyond stn","probabilities":0.9799733,"Title":"The Prognostic Impact Of Positive Lymph Nodes In Stages T1 To T3 Incidental Gallbladder Carcinoma: Results Of The German Registry","Abstract":"Background: In the literature, the 5 year survival rates for incidental gallbladder carcinoma (IGBC) show large variations in the different T-stages because the lymph node status often is not addressed. Most early-stage carcinomas are identified by laparoscopy as IGBC, and radical re-resection is needed. Staging is impossible without lymph node dissection, so comparison between various survival rates is impossible. This study aimed to determine the influence of lymph node status on the survival of patients with stages T1 to T3 IGBC. \r\n\r\n Methods: For data analysis, the German Registry was used. \r\n\r\n Results: In this study, 709 patients with IGBC were analyzed. The re-resected nodal-negative patients had a significant survival advantage over the re-resected nodal-positive patients. The 5 year survival rate for the patients with nodal-negative re-resected T1 carcinomas was 75%. The re-resected T2 and T3 nodal-negative patients had significantly better survival than the corresponding nodal-positive patients. The influence that the radicalness of the different liver resection techniques had on these results was excluded. 53 patients without radical resection had a known nodal-positive status. Nodal-positive patients with radical re-resection always show a better survival rate than nodal-positive patients without radical re-resection, stage for stage. \r\n\r\n Conclusions: Nodal-positive status is a significant negative prognostic factor in T1 to T3 IGBC. Patients with radical re-resection show a better survival rate than those without it. Lymph node dissection is to be highly recommended up to stage T1b. In the case of T2 carcinomas, lymph node dissection of the hepatoduodenal ligament seems to be the minimum volume of lymph node dissection required, but more radical procedures could be beneficial for tumors infiltrating the serosa or beyond.","Source":"STN","category":"HUMAN","training_data":"The Prognostic Impact Of Positive Lymph Nodes In Stages T1 To T3 Incidental Gallbladder Carcinoma: Results Of The German Registry Background: In the literature, the 5 year survival rates for incidental gallbladder carcinoma (IGBC) show large variations in the different T-stages because the lymph node status often is not addressed. Most early-stage carcinomas are identified by laparoscopy as IGBC, and radical re-resection is needed. Staging is impossible without lymph node dissection, so comparison between various survival rates is impossible. This study aimed to determine the influence of lymph node status on the survival of patients with stages T1 to T3 IGBC. \r\n\r\n Methods: For data analysis, the German Registry was used. \r\n\r\n Results: In this study, 709 patients with IGBC were analyzed. The re-resected nodal-negative patients had a significant survival advantage over the re-resected nodal-positive patients. The 5 year survival rate for the patients with nodal-negative re-resected T1 carcinomas was 75%. The re-resected T2 and T3 nodal-negative patients had significantly better survival than the corresponding nodal-positive patients. The influence that the radicalness of the different liver resection techniques had on these results was excluded. 53 patients without radical resection had a known nodal-positive status. Nodal-positive patients with radical re-resection always show a better survival rate than nodal-positive patients without radical re-resection, stage for stage. \r\n\r\n Conclusions: Nodal-positive status is a significant negative prognostic factor in T1 to T3 IGBC. Patients with radical re-resection show a better survival rate than those without it. Lymph node dissection is to be highly recommended up to stage T1b. In the case of T2 carcinomas, lymph node dissection of the hepatoduodenal ligament seems to be the minimum volume of lymph node dissection required, but more radical procedures could be beneficial for tumors infiltrating the serosa or beyond. STN","prediction_labels":"HUMAN"},{"cleaned":"risk hepatobiliary cancer metabolic syndrome nested case control study abstract available google scholar","probabilities":0.9799733,"Title":"The Risk Of Hepatobiliary Cancer With Metabolic Syndrome: A Nested Case-Control Study","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"The Risk Of Hepatobiliary Cancer With Metabolic Syndrome: A Nested Case-Control Study Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"advances diagnosis human opisthorchiasis development opisthorchis viverrini antigen detection urine background many strategies control opisthorchiasis employed thailand neighbouring countries specific control methods include mass drug administration mda health education reduce raw fish consumption control efforts greatly shifted epidemiology opisthorchis viverrini ov infection last decade presenting densely concentrated heavy infections single villages widespread light ov infections distributed wide geographical areas currently gold standard detection method ov infection formalin ethyl acetate concentration technique fect limited diagnostic sensitivity diagnostic specificity light ov infections ov eggs often confused eggs minute intestinal flukes mifs feces study developed evaluated diagnostic performance monoclonal antibody based enzyme linked immunosorbent assay measurement ov excretory secretory es antigens urine urine ov es assay diagnosis opisthorchiasis compared gold standard detection fect method methodology tested several methods pre treating urine samples prior testing diagnostic performance urine ov es assay using trichloroacetic acid tca pre treated urine compared detection quantification ov infection using urine ov es assay versus fect ov endemic areas northeastern thailand receiver operating characteristic roc curves used determine diagnostic sensitivity specificity urine ov es assay using tca pre treated urine establish diagnostic positivity thresholds positive predictive value well likelihood obtaining positive test result lr negative test result lr calculated established diagnostic positivity threshold diagnostic risks odds ratios estimated using logistic regression results urine samples pre treated tca prior use urine ov es assay analytical sensitivity significantly improved using tca pre treatment urine urine ov es assay limit detection lod 39 ng ml compared lod 52 ng ml reported coprological antigen detection methods similarly urine ov es assay correlated significantly intensity ov infection measured fect urine ov es assay also able detect 28 individuals positive 63 44 4 individuals previously determined negative using fect likelihood positive diagnosis ov infection urine ov es assay increased significantly intensity ov infection determined fect reference fect sensitivity specificity urine ov es assay 81 70 respectively conclusion detection ov infection urine ov es assay showed much greater diagnostic sensitivity diagnostic specificity current gold standard fect method detection quantification ov infection due ease use noninvasive sample collection urine urine ov es assay offers potential revolutionize diagnosis liver fluke infection provide effective tool control elimination tumorigenic parasites pubmed","probabilities":1.0,"Title":"Advances in the Diagnosis of Human Opisthorchiasis: Development of Opisthorchis viverrini Antigen Detection in Urine","Abstract":"BACKGROUND: Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated \"heavy\" infections in single villages to widespread \"light\" OV infections distributed over wide geographical areas. Currently, the \"gold standard\" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV eggs often confused with eggs of minute intestinal flukes (MIFs) in feces. In this study, we developed and evaluated the diagnostic performance of a monoclonal antibody-based enzyme-linked immunosorbent assay for the measurement of OV excretory-secretory (ES) antigens in urine (urine OV-ES assay) for the diagnosis of opisthorchiasis compared to the gold standard detection FECT method. METHODOLOGY: We tested several methods for pre-treating urine samples prior to testing the diagnostic performance of the urine OV-ES assay. Using trichloroacetic acid (TCA) pre-treated urine, we compared detection and quantification of OV infection using the urine OV-ES assay versus FECT in OV-endemic areas in Northeastern Thailand. Receiver operating characteristic (ROC) curves were used to determine the diagnostic sensitivity and specificity of the urine OV-ES assay using TCA pre-treated urine, and to establish diagnostic positivity thresholds. The Positive Predictive Value as well as the likelihood of obtaining a positive test result (LR+) or a negative test result (LR-) were calculated for the established diagnostic positivity threshold. Diagnostic risks (Odds Ratios) were estimated using logistic regression. RESULTS: When urine samples were pre-treated with TCA prior to use in the urine OV-ES assay, the analytical sensitivity was significantly improved. Using TCA pre-treatment of urine, the urine OV-ES assay had a limit of detection (LoD) of 39 ng/ml compared to the LoD of 52 ng/mL reported for coprological antigen detection methods. Similarly, the urine OV-ES assay correlated significantly with intensity of OV infection as measured by FECT. The urine OV-ES assay was also able to detect 28 individuals as positive from the 63 (44.4%) individuals previously determined to be negative using FECT. The likelihood of a positive diagnosis of OV infection by urine OV-ES assay increased significantly with the intensity of OV infection as determined by FECT. With reference to FECT, the sensitivity and specificity of the urine OV-ES assay was 81% and 70%, respectively. CONCLUSION: The detection of OV-infection by the urine OV-ES assay showed much greater diagnostic sensitivity and diagnostic specificity than the current \"gold standard\" FECT method for the detection and quantification of OV infection. Due to its ease-of-use, and noninvasive sample collection (urine), the urine OV-ES assay offers the potential to revolutionize the diagnosis of liver fluke infection and provide an effective tool for control and elimination of these tumorigenic parasites.","Source":"PubMed","category":"ANIMAL","training_data":"Advances in the Diagnosis of Human Opisthorchiasis: Development of Opisthorchis viverrini Antigen Detection in Urine BACKGROUND: Many strategies to control opisthorchiasis have been employed in Thailand, but not in the other neighbouring countries. Specific control methods include mass drug administration (MDA) and health education to reduce raw fish consumption. These control efforts have greatly shifted the epidemiology of Opisthorchis viverrini (OV) infection over the last decade from presenting as densely concentrated \"heavy\" infections in single villages to widespread \"light\" OV infections distributed over wide geographical areas. Currently, the \"gold standard\" detection method for OV infection is formalin ethyl-acetate concentration technique (FECT), which has limited diagnostic sensitivity and diagnostic specificity for light OV infections, with OV eggs often confused with eggs of minute intestinal flukes (MIFs) in feces. In this study, we developed and evaluated the diagnostic performance of a monoclonal antibody-based enzyme-linked immunosorbent assay for the measurement of OV excretory-secretory (ES) antigens in urine (urine OV-ES assay) for the diagnosis of opisthorchiasis compared to the gold standard detection FECT method. METHODOLOGY: We tested several methods for pre-treating urine samples prior to testing the diagnostic performance of the urine OV-ES assay. Using trichloroacetic acid (TCA) pre-treated urine, we compared detection and quantification of OV infection using the urine OV-ES assay versus FECT in OV-endemic areas in Northeastern Thailand. Receiver operating characteristic (ROC) curves were used to determine the diagnostic sensitivity and specificity of the urine OV-ES assay using TCA pre-treated urine, and to establish diagnostic positivity thresholds. The Positive Predictive Value as well as the likelihood of obtaining a positive test result (LR+) or a negative test result (LR-) were calculated for the established diagnostic positivity threshold. Diagnostic risks (Odds Ratios) were estimated using logistic regression. RESULTS: When urine samples were pre-treated with TCA prior to use in the urine OV-ES assay, the analytical sensitivity was significantly improved. Using TCA pre-treatment of urine, the urine OV-ES assay had a limit of detection (LoD) of 39 ng/ml compared to the LoD of 52 ng/mL reported for coprological antigen detection methods. Similarly, the urine OV-ES assay correlated significantly with intensity of OV infection as measured by FECT. The urine OV-ES assay was also able to detect 28 individuals as positive from the 63 (44.4%) individuals previously determined to be negative using FECT. The likelihood of a positive diagnosis of OV infection by urine OV-ES assay increased significantly with the intensity of OV infection as determined by FECT. With reference to FECT, the sensitivity and specificity of the urine OV-ES assay was 81% and 70%, respectively. CONCLUSION: The detection of OV-infection by the urine OV-ES assay showed much greater diagnostic sensitivity and diagnostic specificity than the current \"gold standard\" FECT method for the detection and quantification of OV infection. Due to its ease-of-use, and noninvasive sample collection (urine), the urine OV-ES assay offers the potential to revolutionize the diagnosis of liver fluke infection and provide an effective tool for control and elimination of these tumorigenic parasites. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"adjuvant therapy gallbladder bile duct cancers retrospective comparative study purpose study efficacy adjuvant therapy chemotherapy radiotherapy early stages iii gallbladder bile duct cancers methods clinical pathological characteristics treatment details survival data patients operated early stages iii gallbladder bile duct cancers followed clinic august 2002 november 2009 retrospectively evaluated results 52 patients median age 64 years early stages gallbladder n 36 bile duct n 16 cancers analysed twenty three 44 2 patients stage 23 44 2 stage ii 6 11 5 stage iii cancers approximately half patients n 25 48 1 received postoperative adjuvant chemotherapy radiotherapy patients adjuvant treatment younger without 62 vs 71 years p 0 06 eighteen patients received chemotherapy alone 2 chemotherapy followed radiotherapy 1 chemotherapy concurrently radiotherapy 4 radiotherapy alone adjuvant therapy regimen frequently used 57 1 cff cisplatin 50 mg m 2 day 1 folinic acid 200 mg m 2 day 1 5 fluorouracil 5 fu 400 mg m 2 bolus day 1 1600 mg m 2 48h continuous infusion poor prognostic factors like high tumor grade vascular invasion frequent patients received adjuvant therapy median disease free survival dfs 11 4 months patients received adjuvant therapy vs 8 2 months without adjuvant therapy p 0 67 follow 11 patients 44 0 adjuvant therapy 12 44 4 without died p 0 97 estimated median survival 29 months conclusion although previous studies shown 5 fu based adjuvant chemotherapy may provide small survival advantage confirmed present study prospective adjuvant trials standard chemotherapy regimen larger numbers patients required pubmed","probabilities":0.9799733,"Title":"Adjuvant therapy for gallbladder and bile duct cancers: retrospective comparative study","Abstract":"PURPOSE: To study the efficacy of adjuvant therapy (chemotherapy and radiotherapy) in early stages (I-III) of gallbladder and bile duct cancers. METHODS: The clinical and pathological characteristics, treatment details and survival data of patients operated with early stages (I-III) of gallbladder and bile duct cancers and followed up in our clinic between August 2002 - November 2009 were retrospectively evaluated. RESULTS: 52 patients (median age 64 years) with early stages of gallbladder (n=36) and bile duct (n=16) cancers were analysed. Twenty-three (44.2%) patients had stage I, 23 (44.2%) stage II, and 6 (11.5%) stage III cancers. Approximately half of the patients (n=25; 48.1%) received postoperative adjuvant chemotherapy and/or radiotherapy. Patients with adjuvant treatment were younger than those without (62 vs. 71 years, p=0.06). Eighteen patients received chemotherapy alone, 2 chemotherapy followed by radiotherapy, 1 chemotherapy concurrently with radiotherapy, and 4 radiotherapy alone as adjuvant therapy. The regimen most frequently used (57.1%) was CFF (cisplatin 50 mg/m(2), day 1; folinic acid 200 mg/m(2), day 1; 5-fluorouracil [5-FU] 400 mg/m(2) bolus day 1 and 1600 mg/m(2) 48h continuous infusion). Some poor prognostic factors like high tumor grade and vascular invasion were more frequent in patients who received adjuvant therapy. The median disease free survival (DFS) was 11.4 months for the patients that received adjuvant therapy vs. 8.2 months for those without adjuvant therapy (p=0.67). During follow up 11 patients (44.0%) with adjuvant therapy and 12 (44.4%) without have died (p=0.97). The estimated median survival was 29 months. CONCLUSION: Although previous studies had shown that 5-FU-based adjuvant chemotherapy may provide a small survival advantage, this was not confirmed in the present study. Prospective adjuvant trials with a standard chemotherapy regimen and larger numbers of patients are required.","Source":"PubMed","category":"HUMAN","training_data":"Adjuvant therapy for gallbladder and bile duct cancers: retrospective comparative study PURPOSE: To study the efficacy of adjuvant therapy (chemotherapy and radiotherapy) in early stages (I-III) of gallbladder and bile duct cancers. METHODS: The clinical and pathological characteristics, treatment details and survival data of patients operated with early stages (I-III) of gallbladder and bile duct cancers and followed up in our clinic between August 2002 - November 2009 were retrospectively evaluated. RESULTS: 52 patients (median age 64 years) with early stages of gallbladder (n=36) and bile duct (n=16) cancers were analysed. Twenty-three (44.2%) patients had stage I, 23 (44.2%) stage II, and 6 (11.5%) stage III cancers. Approximately half of the patients (n=25; 48.1%) received postoperative adjuvant chemotherapy and/or radiotherapy. Patients with adjuvant treatment were younger than those without (62 vs. 71 years, p=0.06). Eighteen patients received chemotherapy alone, 2 chemotherapy followed by radiotherapy, 1 chemotherapy concurrently with radiotherapy, and 4 radiotherapy alone as adjuvant therapy. The regimen most frequently used (57.1%) was CFF (cisplatin 50 mg/m(2), day 1; folinic acid 200 mg/m(2), day 1; 5-fluorouracil [5-FU] 400 mg/m(2) bolus day 1 and 1600 mg/m(2) 48h continuous infusion). Some poor prognostic factors like high tumor grade and vascular invasion were more frequent in patients who received adjuvant therapy. The median disease free survival (DFS) was 11.4 months for the patients that received adjuvant therapy vs. 8.2 months for those without adjuvant therapy (p=0.67). During follow up 11 patients (44.0%) with adjuvant therapy and 12 (44.4%) without have died (p=0.97). The estimated median survival was 29 months. CONCLUSION: Although previous studies had shown that 5-FU-based adjuvant chemotherapy may provide a small survival advantage, this was not confirmed in the present study. Prospective adjuvant trials with a standard chemotherapy regimen and larger numbers of patients are required. PubMed","prediction_labels":"HUMAN"},{"cleaned":"potent prognostic impact lymph node ratio survival resection extrahepatic cholangiocarcinoma aim studies investigated influence lymph node ratio lnr ratio number lymph nodes harboring metastatic cancer total number lymph nodes removed outcome surgery extrahepatic cholangiocarcinoma study conducted examine prognostic impact lnr patients undergoing resection extrahepatic cholangiocarcinoma patients methods retrospectively analyzed total 60 consecutive patients underwent resection extrahepatic cholangiocarcinoma focused lnr classified 0 34 patients 0 0 2 13 patients greater 0 2 13 patients results overall five year survival rates patients lnrs 0 0 0 2 0 2 44 10 0 respectively p 0 023 lnr independent predictive factor estimated survival univariate p 0 016 multivariate p 0 022 analyses including lnr sites primary tumors surgical margin variables statistically significant differences patients less 12 lymph nodes removed 12 lymph nodes removed p 0 484 conclusion lnr powerful independent predictor estimated survival patients undergoing surgical resection extrahepatic cholangiocarcinoma lnr considered stratifying patients future clinical trials stn","probabilities":0.9799733,"Title":"Potent Prognostic Impact Of The Lymph Node Ratio On Survival After Resection For Extrahepatic Cholangiocarcinoma","Abstract":"Aim: Few studies have investigated the influence of the lymph node ratio (LNR), the ratio of the number of lymph nodes harboring metastatic cancer to the total number of lymph nodes removed, on the outcome after surgery for extrahepatic cholangiocarcinoma. This study was conducted to examine the prognostic impact of LNR in patients undergoing resection for extrahepatic cholangiocarcinoma. \r\n\r\n Patients and methods: We retrospectively analyzed a total of 60 consecutive patients who underwent resection for extrahepatic cholangiocarcinoma. We focused on the LNR, which was classified as 0 in 34 patients, between 0 and 0.2 in 13 patients, and greater than 0.2 in 13 patients. \r\n\r\n Results: The overall five-year survival rates for patients with LNRs of 0, 0 to 0.2, and ≥0.2 were 44%, 10%, and 0%, respectively (p = 0.023). LNR was an independent predictive factor for estimated survival by both univariate (p = 0.016) and multivariate (p = 0.022) analyses including LNR, the sites of the primary tumors, and surgical margin as the variables. There were no statistically significant differences between patients who had less than 12 lymph nodes removed and those who had 12 or more lymph nodes removed (p = 0.484). \r\n\r\n Conclusion: LNR was a powerful, independent predictor of estimated survival in patients undergoing surgical resection for extrahepatic cholangiocarcinoma. LNR should be considered when stratifying patients for future clinical trials.","Source":"STN","category":"HUMAN","training_data":"Potent Prognostic Impact Of The Lymph Node Ratio On Survival After Resection For Extrahepatic Cholangiocarcinoma Aim: Few studies have investigated the influence of the lymph node ratio (LNR), the ratio of the number of lymph nodes harboring metastatic cancer to the total number of lymph nodes removed, on the outcome after surgery for extrahepatic cholangiocarcinoma. This study was conducted to examine the prognostic impact of LNR in patients undergoing resection for extrahepatic cholangiocarcinoma. \r\n\r\n Patients and methods: We retrospectively analyzed a total of 60 consecutive patients who underwent resection for extrahepatic cholangiocarcinoma. We focused on the LNR, which was classified as 0 in 34 patients, between 0 and 0.2 in 13 patients, and greater than 0.2 in 13 patients. \r\n\r\n Results: The overall five-year survival rates for patients with LNRs of 0, 0 to 0.2, and ≥0.2 were 44%, 10%, and 0%, respectively (p = 0.023). LNR was an independent predictive factor for estimated survival by both univariate (p = 0.016) and multivariate (p = 0.022) analyses including LNR, the sites of the primary tumors, and surgical margin as the variables. There were no statistically significant differences between patients who had less than 12 lymph nodes removed and those who had 12 or more lymph nodes removed (p = 0.484). \r\n\r\n Conclusion: LNR was a powerful, independent predictor of estimated survival in patients undergoing surgical resection for extrahepatic cholangiocarcinoma. LNR should be considered when stratifying patients for future clinical trials. STN","prediction_labels":"HUMAN"},{"cleaned":"gemcitabine plus cisplatin advanced biliary tract cancer systematic review evidence suggests combined gemcitabine cisplatin chemotherapy extends survival patients advanced biliary tract cancer btc conducted systematic review order collate evidence assess whether gemcitabine cisplatin efficacy influenced primary tumor site disease stage geographic region whether associated toxicities related regimen medline 1946 search date embase 1966 search date clinicaltrials gov 2008 search date abstracts major oncology conferences 2009 search date searched 5 dec 2013 using terms btc gemcitabine cisplatin study types reporting efficacy survival response rates safety toxicities outcomes gemcitabine cisplatin btc eligible inclusion efficacy data extracted prospective studies evidence retrieved one meta analysis abstract four randomized controlled trials 12 nonrandomized prospective studies three retrospective studies supported efficacy safety gemcitabine cisplatin btc median overall survival ranged 4 6 11 7 months response rate ranged 17 1 36 6 toxicities generally acceptable manageable heterogeneity study designs data collected prevented formal meta analysis however exploratory assessments suggested efficacy vary primary tumor site gallbladder vs others disease stage metastatic vs locally advanced geographic origin asia vs incidence grade 3 4 toxicities related gemcitabine dose cisplatin frequency despite individual variation study designs evidence presented suggests gemcitabine cisplatin effective patients diverse range countries heterogeneous disease characteristics substantial differences toxicity observed among different dosing schedules gemcitabine cisplatin google scholar","probabilities":0.9799733,"Title":"Gemcitabine Plus Cisplatin For Advanced Biliary Tract Cancer: A Systematic Review","Abstract":"Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends survival in patients with advanced biliary tract cancer (BTC). We conducted a systematic review in order to collate this evidence and assess whether gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease stage, or geographic region, and whether associated toxicities are related to regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials. gov (2008-search date), and abstracts from major oncology conferences (2009- search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and cisplatin. All study types reporting efficacy (survival, response rates) or safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for inclusion; efficacy data were extracted from prospective studies only. Evidence retrieved from one meta-analysis (abstract), four randomized controlled trials, 12 nonrandomized prospective studies, and three retrospective studies supported the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable. Heterogeneity in study designs and data collected prevented formal meta-analysis, however exploratory assessments suggested that efficacy did not vary with primary tumor site (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency. Despite individual variation in study designs, the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics. No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin.","Source":"Google Scholar","category":"HUMAN","training_data":"Gemcitabine Plus Cisplatin For Advanced Biliary Tract Cancer: A Systematic Review Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends survival in patients with advanced biliary tract cancer (BTC). We conducted a systematic review in order to collate this evidence and assess whether gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease stage, or geographic region, and whether associated toxicities are related to regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials. gov (2008-search date), and abstracts from major oncology conferences (2009- search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and cisplatin. All study types reporting efficacy (survival, response rates) or safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for inclusion; efficacy data were extracted from prospective studies only. Evidence retrieved from one meta-analysis (abstract), four randomized controlled trials, 12 nonrandomized prospective studies, and three retrospective studies supported the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable. Heterogeneity in study designs and data collected prevented formal meta-analysis, however exploratory assessments suggested that efficacy did not vary with primary tumor site (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency. Despite individual variation in study designs, the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics. No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"chd1l associated poor survival promotes proliferation metastasis intrahepatic cholangiocarcinoma chromodomain helicase atpase dna binding protein 1 like gene chd1l new oncogene confirmed crucial progression many solid tumors present study expression chd1l found upregulated intrahepatic cholangiocarcinoma icc significantly associated histological differentiation p 0 011 vascular invasion p 0 002 lymph node metastasis p 0 008 tnm stage p 0 001 kaplan meier survival analysis revealed icc patients positive chd1l expression shorter overall disease free survival negative chd1l expression functional study found chd1l exhibited strong oncogenic roles including increased cell growth cck 8 assay colony formation plate colony formation assay g1 transition flow cytometry tumor formation nude mice addition rnai mediated silencing chd1l inhibited icc invasion metastasis wound healing transwell migration matrigel invasion assays vitro vivo collectively results show chd1l upregulated promotes proliferation metastasis icc cells chd1l acts oncogene may prognostic factor therapeutic target patients icc google scholar","probabilities":0.9467213,"Title":"Chd1L Is Associated With Poor Survival And Promotes The Proliferation And Metastasis Of Intrahepatic Cholangiocarcinoma","Abstract":"Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L) is a new oncogene which has been confirmed to be crucial to the progression of many solid tumors. In the present study, the expression of CHD1L was found to be upregulated in intrahepatic cholangiocarcinoma (ICC), which was significantly associated with histological differentiation (P=0.011), vascular invasion (P=0.002), lymph node metastasis (P=0.008) and TNM stage (P=0.001). Kaplan-Meier survival analysis revealed that ICC patients with positive CHD1L expression had shorter overall and disease-free survival than those with negative CHD1L expression. Functional study found that CHD1L exhibited strong oncogenic roles, including increased cell growth by CCK-8 assay, colony formation by plate colony formation assay, G1/S transition by flow cytometry and tumor formation in nude mice. In addition, RNAi-mediated silencing of CHD1L inhibited ICC invasion and metastasis by wound healing, Transwell migration and Matrigel invasion assays in vitro and in vivo. Collectively, our results show that CHD1L is upregulated and promotes the proliferation and metastasis of ICC cells. CHD1L acts as an oncogene and may be a prognostic factor or therapeutic target for patients with ICC.","Source":"Google Scholar","category":"ANIMAL","training_data":"Chd1L Is Associated With Poor Survival And Promotes The Proliferation And Metastasis Of Intrahepatic Cholangiocarcinoma Chromodomain helicase/ATPase DNA-binding protein 1-like gene (CHD1L) is a new oncogene which has been confirmed to be crucial to the progression of many solid tumors. In the present study, the expression of CHD1L was found to be upregulated in intrahepatic cholangiocarcinoma (ICC), which was significantly associated with histological differentiation (P=0.011), vascular invasion (P=0.002), lymph node metastasis (P=0.008) and TNM stage (P=0.001). Kaplan-Meier survival analysis revealed that ICC patients with positive CHD1L expression had shorter overall and disease-free survival than those with negative CHD1L expression. Functional study found that CHD1L exhibited strong oncogenic roles, including increased cell growth by CCK-8 assay, colony formation by plate colony formation assay, G1/S transition by flow cytometry and tumor formation in nude mice. In addition, RNAi-mediated silencing of CHD1L inhibited ICC invasion and metastasis by wound healing, Transwell migration and Matrigel invasion assays in vitro and in vivo. Collectively, our results show that CHD1L is upregulated and promotes the proliferation and metastasis of ICC cells. CHD1L acts as an oncogene and may be a prognostic factor or therapeutic target for patients with ICC. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"investigation spatial clustering biliary tract cancer incidence osaka japan neighborhood effect printing factory background 2013 unusually high incidence biliary tract cancer among current former workers offset color proof printing department printing company osaka japan reported purpose study examine whether distance printing factory associated incidence biliary tract cancer whether incident biliary tract cancer cases clustered around printing factory osaka using population based cancer registry data methods estimated age standardized incidence ratio biliary tract cancer according distance printing factory also searched clusters biliary tract cancer incidence using spatial scan statistics results observe statistically significantly high low standardized incidence ratios residents area categorized distance printing factory entire sample either sex scan statistics show statistically significant clustering biliary tract cancer incidence anywhere osaka prefecture 2004 2007 conclusions statistically significant clustering biliary tract cancer incidence around printing factory areas osaka japan 2004 2007 date even substances diffused outside source factory appear influenced incidence biliary tract cancer neighboring residents stn","probabilities":0.9799733,"Title":"Investigation Of Spatial Clustering Of Biliary Tract Cancer Incidence In Osaka Japan: Neighborhood Effect Of A Printing Factory","Abstract":"Background: In 2013, an unusually high incidence of biliary tract cancer among current or former workers of the offset color proof printing department of a printing company in Osaka, Japan, was reported. The purpose of this study was to examine whether distance from the printing factory was associated with incidence of biliary tract cancer and whether incident biliary tract cancer cases clustered around the printing factory in Osaka using population-based cancer registry data. \r\n\r\n Methods: We estimated the age-standardized incidence ratio of biliary tract cancer according to distance from this printing factory. We also searched for clusters of biliary tract cancer incidence using spatial scan statistics. \r\n\r\n Results: We did not observe statistically significantly high or low standardized incidence ratios for residents in each area categorized by distance from the printing factory for the entire sample or for either sex. The scan statistics did not show any statistically significant clustering of biliary tract cancer incidence anywhere in Osaka prefecture in 2004-2007. \r\n\r\n Conclusions: There was no statistically significant clustering of biliary tract cancer incidence around the printing factory or in any other areas in Osaka, Japan, between 2004 and 2007. To date, even if some substances have diffused outside this source factory, they do not appear to have influenced the incidence of biliary tract cancer in neighboring residents.","Source":"STN","category":"HUMAN","training_data":"Investigation Of Spatial Clustering Of Biliary Tract Cancer Incidence In Osaka Japan: Neighborhood Effect Of A Printing Factory Background: In 2013, an unusually high incidence of biliary tract cancer among current or former workers of the offset color proof printing department of a printing company in Osaka, Japan, was reported. The purpose of this study was to examine whether distance from the printing factory was associated with incidence of biliary tract cancer and whether incident biliary tract cancer cases clustered around the printing factory in Osaka using population-based cancer registry data. \r\n\r\n Methods: We estimated the age-standardized incidence ratio of biliary tract cancer according to distance from this printing factory. We also searched for clusters of biliary tract cancer incidence using spatial scan statistics. \r\n\r\n Results: We did not observe statistically significantly high or low standardized incidence ratios for residents in each area categorized by distance from the printing factory for the entire sample or for either sex. The scan statistics did not show any statistically significant clustering of biliary tract cancer incidence anywhere in Osaka prefecture in 2004-2007. \r\n\r\n Conclusions: There was no statistically significant clustering of biliary tract cancer incidence around the printing factory or in any other areas in Osaka, Japan, between 2004 and 2007. To date, even if some substances have diffused outside this source factory, they do not appear to have influenced the incidence of biliary tract cancer in neighboring residents. STN","prediction_labels":"HUMAN"},{"cleaned":"role 5 hydroxymethylcytosine level diagnosis prognosis prediction intrahepatic cholangiocarcinoma loss 5 hydroxymethylcytosine 5 hmc identified epigenetic hallmark several malignancies however role intrahepatic cholangiocarcinoma icc still unknown study aims investigate level 5 hmc diagnosis prognosis prediction icc 5 hmc levels detected using dot blot tissue microarray technique immunohistochemical method correlation 5 hmc level icc clinicopathological parameters analysed compared matched liver tissues icc tissues presented loss 5 hmc furthermore subgroups cirrhotic poor differentiation tissues showed lowest level 5 hmc found 5 hmc level non elevated icc patients significantly related lymph node metastasis tnm stage related vessel invasion sex age hbv cirrhosis degree differentiation icc patients high tnm stage stages iii iv lymph node metastases significantly lower 5 hmc level low tnm stage stages ii lymph node metastases analysis showed low 5 hmc level significantly correlated worse overall survival os disease free survival dfs importantly multivariate analysis indicated 5 hmc level tumour diameter lymphatic metastasis tumour differentiation used independent prognostic factors icc loss 5 hmc implicated progression icc results contribute diagnostic ability postoperative surveillance icc patients stn","probabilities":0.9285714,"Title":"Role Of 5-Hydroxymethylcytosine Level In Diagnosis And Prognosis Prediction Of Intrahepatic Cholangiocarcinoma","Abstract":"The loss of 5-hydroxymethylcytosine (5-hmC) has been identified as an epigenetic hallmark in several malignancies. However, its role in intrahepatic cholangiocarcinoma (ICC) is still unknown. Our study aims to investigate the level of 5-hmC in diagnosis and prognosis prediction of ICC. The 5-hmC levels were detected using dot blot, tissue microarray technique and immunohistochemical method, and the correlation between 5-hmC level and ICC clinicopathological parameters was analysed. Compared with matched liver tissues, most of ICC tissues presented with the loss of 5-hmC. Furthermore, the subgroups of cirrhotic and poor differentiation tissues showed the lowest level of 5-hmC. We found that 5-hmC level in non-elevated ICC patients was significantly related to lymph node metastasis and TNM stage and not related to vessel invasion, sex, age, HBV, cirrhosis or degree of differentiation. ICC patients with high TNM stage (stages III and IV) and lymph node metastases had significantly lower 5-hmC level than those with low TNM stage (stages I and II) and no lymph node metastases. Further analysis showed that low 5-hmC level is significantly correlated with worse overall survival (OS) and disease-free survival (DFS). Importantly, multivariate analysis indicated that 5-hmC level, tumour diameter, lymphatic metastasis and tumour differentiation could be used as independent prognostic factors for ICC. The loss of 5-hmC is implicated in the progression of ICC. Our results can contribute to the diagnostic ability and postoperative surveillance of ICC patients.","Source":"STN","category":"ANIMAL","training_data":"Role Of 5-Hydroxymethylcytosine Level In Diagnosis And Prognosis Prediction Of Intrahepatic Cholangiocarcinoma The loss of 5-hydroxymethylcytosine (5-hmC) has been identified as an epigenetic hallmark in several malignancies. However, its role in intrahepatic cholangiocarcinoma (ICC) is still unknown. Our study aims to investigate the level of 5-hmC in diagnosis and prognosis prediction of ICC. The 5-hmC levels were detected using dot blot, tissue microarray technique and immunohistochemical method, and the correlation between 5-hmC level and ICC clinicopathological parameters was analysed. Compared with matched liver tissues, most of ICC tissues presented with the loss of 5-hmC. Furthermore, the subgroups of cirrhotic and poor differentiation tissues showed the lowest level of 5-hmC. We found that 5-hmC level in non-elevated ICC patients was significantly related to lymph node metastasis and TNM stage and not related to vessel invasion, sex, age, HBV, cirrhosis or degree of differentiation. ICC patients with high TNM stage (stages III and IV) and lymph node metastases had significantly lower 5-hmC level than those with low TNM stage (stages I and II) and no lymph node metastases. Further analysis showed that low 5-hmC level is significantly correlated with worse overall survival (OS) and disease-free survival (DFS). Importantly, multivariate analysis indicated that 5-hmC level, tumour diameter, lymphatic metastasis and tumour differentiation could be used as independent prognostic factors for ICC. The loss of 5-hmC is implicated in the progression of ICC. Our results can contribute to the diagnostic ability and postoperative surveillance of ICC patients. STN","prediction_labels":"ANIMAL"},{"cleaned":"primary sclerosing cholangitis cholangiocarcinoma pathogenesis modes diagnostics primary sclerosing cholangitis psc chronic cholestatic liver disease caused progressive inflammation intra extrahepatic bile duct system psc patients increased risk develop hepatobiliary well extrahepatic malignancies goal surveillance strategy hepatobiliary malignancy patients detection early cancer allow potentially curative therapy focus conceptual review pathogenesis cholangiocellular carcinoma gallbladder cancer discuss rational approach surveillance malignancies psc patients pubmed","probabilities":0.9799733,"Title":"Primary sclerosing cholangitis and cholangiocarcinoma: pathogenesis and modes of diagnostics","Abstract":"Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease caused by progressive inflammation of the intra- and extrahepatic bile duct system. PSC patients have an increased risk to develop hepatobiliary as well as extrahepatic malignancies. The goal of a surveillance strategy for hepatobiliary malignancy in these patients is the detection of early cancer which will allow a potentially curative therapy. Here, we focus on a conceptual review of the pathogenesis of cholangiocellular carcinoma and gallbladder cancer and we will discuss a rational approach for the surveillance of these malignancies in PSC patients.","Source":"PubMed","category":"HUMAN","training_data":"Primary sclerosing cholangitis and cholangiocarcinoma: pathogenesis and modes of diagnostics Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease caused by progressive inflammation of the intra- and extrahepatic bile duct system. PSC patients have an increased risk to develop hepatobiliary as well as extrahepatic malignancies. The goal of a surveillance strategy for hepatobiliary malignancy in these patients is the detection of early cancer which will allow a potentially curative therapy. Here, we focus on a conceptual review of the pathogenesis of cholangiocellular carcinoma and gallbladder cancer and we will discuss a rational approach for the surveillance of these malignancies in PSC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumor microenvironment versus cancer stem cells cholangiocarcinoma synergistic effects cholangiocarcinoma ccas may defined tumors derived biliary tree differentiation biliary epithelial cells tumor malignant extremely aggressive poor prognosis treated surgically pathogenesis poorly understood tumor microenvironment tme important factor regulation tumor angiogenesis invasion metastasis besides cancer stem cells cscs modulate tumor growth stroma formation migratory capability initial stage tumorigenesis characterized genetic mutations epigenetic alterations due intrinsic factors lead generation oncogenes thus inducing tumorigenesis cscs may result precancerous stem cells cell de differentiation normal stem cells epithelial mesenchymal transition emt cscs found cancer niche emt may occur early within tumor microenvironment previous studies demonstrated evidence cholangiocarcinoma stem cells cd133 cd24 epcam cd44 others presence markers associated malignant potential interaction tme cholangiocarcinoma stem cells via signaling mediators may create environment accommodates tumor growth yielding resistance cytotoxic insults chemotherarapeutic progress made understanding mechanisms interactions tumorigenic process still remain major challenge review addresses recent concepts tme cscs interaction emphasize importance early detection use novel diagnostic mechanisms cca csc biomarkers importance tumor stroma define new treatments j cell physiol 231 768 776 2016 2015 wiley periodicals inc pubmed","probabilities":0.962963,"Title":"Tumor Microenvironment Versus Cancer Stem Cells in Cholangiocarcinoma: Synergistic Effects?","Abstract":"Cholangiocarcinoma (CCAs) may be defined as tumors that derived from the biliary tree with the differentiation in the biliary epithelial cells. This tumor is malignant, extremely aggressive with a poor prognosis. It can be treated surgically and its pathogenesis is poorly understood. The tumor microenvironment (TME) is a very important factor in the regulation of tumor angiogenesis, invasion, and metastasis. Besides cancer stem cells (CSCs) can modulate tumor growth, stroma formation, and migratory capability. The initial stage of tumorigenesis is characterized by genetic mutations and epigenetic alterations due to intrinsic factors which lead to the generation of oncogenes thus inducing tumorigenesis. CSCs may result from precancerous stem cells, cell de-differentiation, normal stem cells, or an epithelial-mesenchymal transition (EMT). CSCs have been found in the cancer niche, and EMT may occur early within the tumor microenvironment. Previous studies have demonstrated evidence of cholangiocarcinoma stem cells (CD133, CD24, EpCAM, CD44, and others) and the presence of these markers has been associated with malignant potential. The interaction between TME and cholangiocarcinoma stem cells via signaling mediators may create an environment that accommodates tumor growth, yielding resistance to cytotoxic insults (chemotherarapeutic). While progress has been made in the understanding of the mechanisms, the interactions in the tumorigenic process still remain a major challenge. Our review, addresses recent concepts of TME-CSCs interaction and will emphasize the importance of early detection with the use of novel diagnostic mechanisms such as CCA-CSC biomarkers and the importance of tumor stroma to define new treatments. J. Cell. Physiol. 231: 768-776, 2016. © 2015 Wiley Periodicals, Inc.","Source":"PubMed","category":"HUMAN","training_data":"Tumor Microenvironment Versus Cancer Stem Cells in Cholangiocarcinoma: Synergistic Effects? Cholangiocarcinoma (CCAs) may be defined as tumors that derived from the biliary tree with the differentiation in the biliary epithelial cells. This tumor is malignant, extremely aggressive with a poor prognosis. It can be treated surgically and its pathogenesis is poorly understood. The tumor microenvironment (TME) is a very important factor in the regulation of tumor angiogenesis, invasion, and metastasis. Besides cancer stem cells (CSCs) can modulate tumor growth, stroma formation, and migratory capability. The initial stage of tumorigenesis is characterized by genetic mutations and epigenetic alterations due to intrinsic factors which lead to the generation of oncogenes thus inducing tumorigenesis. CSCs may result from precancerous stem cells, cell de-differentiation, normal stem cells, or an epithelial-mesenchymal transition (EMT). CSCs have been found in the cancer niche, and EMT may occur early within the tumor microenvironment. Previous studies have demonstrated evidence of cholangiocarcinoma stem cells (CD133, CD24, EpCAM, CD44, and others) and the presence of these markers has been associated with malignant potential. The interaction between TME and cholangiocarcinoma stem cells via signaling mediators may create an environment that accommodates tumor growth, yielding resistance to cytotoxic insults (chemotherarapeutic). While progress has been made in the understanding of the mechanisms, the interactions in the tumorigenic process still remain a major challenge. Our review, addresses recent concepts of TME-CSCs interaction and will emphasize the importance of early detection with the use of novel diagnostic mechanisms such as CCA-CSC biomarkers and the importance of tumor stroma to define new treatments. J. Cell. Physiol. 231: 768-776, 2016. © 2015 Wiley Periodicals, Inc. PubMed","prediction_labels":"HUMAN"},{"cleaned":"infection opisthorchis felineus induces intraepithelial neoplasia biliary tract rodent model liver fluke opisthorchis felineus member triad epidemiologically relevant species trematode family opisthorchiidae causative agent opisthorchiasis felinea extensive range spans regions eurasia international agency research cancer classifies infection liver flukes opisthorchis viverrini clonorchis sinensis group 1 agents major risk factor cholangiocarcinoma however carcinogenic potential infection o felineus less clear present findings support inclusion o felineus group 1 list biological carcinogens two discrete lines evidence support notion infection liver fluke carcinogenic first novel oxysterol like metabolites detected liquid chromatography mass spectroscopy egg adult developmental stages o felineus bile sera urine liver fluke infected hamsters exhibited marked similarity oxysterol like molecules known o viverrini numerous oxysterols related dna adducts detected liver fluke eggs bile infected hamsters suggested infection associated oxysterols induced chromosomal lesions host cells second histological analysis liver sections hamsters infected o felineus confirmed portal area enlargement inflammation severe periductal fibrosis changes epithelium biliary tract characterized biliary intraepithelial neoplasia bilin consonance biochemical histopathological changes revealed o felineus infection rodent model induced precancerous lesions conducive malignancy stn","probabilities":0.9799733,"Title":"Infection With Opisthorchis Felineus Induces Intraepithelial Neoplasia Of The Biliary Tract In A Rodent Model","Abstract":"The liver fluke Opisthorchis felineus is a member of the triad of epidemiologically relevant species of the trematode family Opisthorchiidae, and the causative agent of opisthorchiasis felinea over an extensive range that spans regions of Eurasia. The International Agency for Research on Cancer classifies the infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis as group 1 agents and a major risk factor for cholangiocarcinoma. However, the carcinogenic potential of the infection with O. felineus is less clear. Here, we present findings that support the inclusion of O. felineus in the Group 1 list of biological carcinogens. Two discrete lines of evidence support the notion that infection with this liver fluke is carcinogenic. First, novel oxysterol-like metabolites detected by liquid chromatography-mass spectroscopy in the egg and adult developmental stages of O. felineus, and in bile, sera, and urine of liver fluke-infected hamsters exhibited marked similarity to oxysterol-like molecules known from O. viverrini. Numerous oxysterols and related DNA-adducts detected in the liver fluke eggs and in bile from infected hamsters suggested that infection-associated oxysterols induced chromosomal lesions in host cells. Second, histological analysis of liver sections from hamsters infected with O. felineus confirmed portal area enlargement, inflammation with severe periductal fibrosis and changes in the epithelium of the biliary tract characterized as biliary intraepithelial neoplasia, BilIN. The consonance of these biochemical and histopathological changes revealed that O. felineus infection in this rodent model induced precancerous lesions conducive to malignancy.","Source":"STN","category":"ANIMAL","training_data":"Infection With Opisthorchis Felineus Induces Intraepithelial Neoplasia Of The Biliary Tract In A Rodent Model The liver fluke Opisthorchis felineus is a member of the triad of epidemiologically relevant species of the trematode family Opisthorchiidae, and the causative agent of opisthorchiasis felinea over an extensive range that spans regions of Eurasia. The International Agency for Research on Cancer classifies the infection with the liver flukes Opisthorchis viverrini and Clonorchis sinensis as group 1 agents and a major risk factor for cholangiocarcinoma. However, the carcinogenic potential of the infection with O. felineus is less clear. Here, we present findings that support the inclusion of O. felineus in the Group 1 list of biological carcinogens. Two discrete lines of evidence support the notion that infection with this liver fluke is carcinogenic. First, novel oxysterol-like metabolites detected by liquid chromatography-mass spectroscopy in the egg and adult developmental stages of O. felineus, and in bile, sera, and urine of liver fluke-infected hamsters exhibited marked similarity to oxysterol-like molecules known from O. viverrini. Numerous oxysterols and related DNA-adducts detected in the liver fluke eggs and in bile from infected hamsters suggested that infection-associated oxysterols induced chromosomal lesions in host cells. Second, histological analysis of liver sections from hamsters infected with O. felineus confirmed portal area enlargement, inflammation with severe periductal fibrosis and changes in the epithelium of the biliary tract characterized as biliary intraepithelial neoplasia, BilIN. The consonance of these biochemical and histopathological changes revealed that O. felineus infection in this rodent model induced precancerous lesions conducive to malignancy. STN","prediction_labels":"HUMAN"},{"cleaned":"efficacy neoadjuvant chemoradiation followed liver transplantation perihilar cholangiocarcinoma 12 us centers background aims excellent single center outcomes neoadjuvant chemoradiation liver transplantation unresectable perihilar cholangiocarcinoma caused united network organ sharing offer standardized model end stage liver disease meld exception disease analyzed data multiple centers determine effectiveness treatment appropriateness meld exception methods collected analyzed data 12 large volume transplant centers united states centers met inclusion criteria treating 3 patients perihilar cholangiocarcinoma using neoadjuvant therapy followed liver transplantation 1993 2010 n 287 total patients center specific protocols medical charts reviewed site results patients completed external radiation 99 brachytherapy 75 radiosensitizing therapy 98 maintenance chemotherapy 65 seventy one patients dropped liver transplantation rate 11 5 3 months intent treat survival rates 68 53 2 5 years therapy respectively post transplant recurrence free survival rates 78 65 respectively patients outside united network organ sharing criteria tumor mass 3 cm transperitoneal tumor biopsy metastatic disease prior malignancy significantly shorter survival times p 001 differences outcomes among patients based differences surgical staging brachytherapy although patients came 1 center n 193 11 centers similar survival times therapy conclusions patients perihilar cholangiocarcinoma treated neoadjuvant therapy followed liver transplantation 12 us centers 65 rate recurrence free survival 5 years showing therapy highly effective 11 5 drop rate 3 5 months therapy indicates appropriateness meld exception rigorous selection important continued success treatment pubmed","probabilities":0.9799733,"Title":"Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers","Abstract":"BACKGROUND & AIMS: Excellent single-center outcomes of neoadjuvant chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma caused the United Network of Organ Sharing to offer a standardized model of end-stage liver disease (MELD) exception for this disease. We analyzed data from multiple centers to determine the effectiveness of this treatment and the appropriateness of the MELD exception. METHODS: We collected and analyzed data from 12 large-volume transplant centers in the United States. These centers met the inclusion criteria of treating 3 or more patients with perihilar cholangiocarcinoma using neoadjuvant therapy, followed by liver transplantation, from 1993 to 2010 (n = 287 total patients). Center-specific protocols and medical charts were reviewed on-site. RESULTS: The patients completed external radiation (99%), brachytherapy (75%), radiosensitizing therapy (98%), and/or maintenance chemotherapy (65%). Seventy-one patients dropped out before liver transplantation (rate, 11.5% in 3 months). Intent-to-treat survival rates were 68% and 53%, 2 and 5 years after therapy, respectively; post-transplant, recurrence-free survival rates were 78% and 65%, respectively. Patients outside the United Network of Organ Sharing criteria (those with tumor mass >3 cm, transperitoneal tumor biopsy, or metastatic disease) or with a prior malignancy had significantly shorter survival times (P < .001). There were no differences in outcomes among patients based on differences in surgical staging or brachytherapy. Although most patients came from 1 center (n = 193), the other 11 centers had similar survival times after therapy. CONCLUSIONS: Patients with perihilar cholangiocarcinoma who were treated with neoadjuvant therapy followed up by liver transplantation at 12 US centers had a 65% rate of recurrence-free survival after 5 years, showing this therapy to be highly effective. An 11.5% drop-out rate after 3.5 months of therapy indicates the appropriateness of the MELD exception. Rigorous selection is important for the continued success of this treatment.","Source":"PubMed","category":"HUMAN","training_data":"Efficacy of neoadjuvant chemoradiation, followed by liver transplantation, for perihilar cholangiocarcinoma at 12 US centers BACKGROUND & AIMS: Excellent single-center outcomes of neoadjuvant chemoradiation and liver transplantation for unresectable perihilar cholangiocarcinoma caused the United Network of Organ Sharing to offer a standardized model of end-stage liver disease (MELD) exception for this disease. We analyzed data from multiple centers to determine the effectiveness of this treatment and the appropriateness of the MELD exception. METHODS: We collected and analyzed data from 12 large-volume transplant centers in the United States. These centers met the inclusion criteria of treating 3 or more patients with perihilar cholangiocarcinoma using neoadjuvant therapy, followed by liver transplantation, from 1993 to 2010 (n = 287 total patients). Center-specific protocols and medical charts were reviewed on-site. RESULTS: The patients completed external radiation (99%), brachytherapy (75%), radiosensitizing therapy (98%), and/or maintenance chemotherapy (65%). Seventy-one patients dropped out before liver transplantation (rate, 11.5% in 3 months). Intent-to-treat survival rates were 68% and 53%, 2 and 5 years after therapy, respectively; post-transplant, recurrence-free survival rates were 78% and 65%, respectively. Patients outside the United Network of Organ Sharing criteria (those with tumor mass >3 cm, transperitoneal tumor biopsy, or metastatic disease) or with a prior malignancy had significantly shorter survival times (P < .001). There were no differences in outcomes among patients based on differences in surgical staging or brachytherapy. Although most patients came from 1 center (n = 193), the other 11 centers had similar survival times after therapy. CONCLUSIONS: Patients with perihilar cholangiocarcinoma who were treated with neoadjuvant therapy followed up by liver transplantation at 12 US centers had a 65% rate of recurrence-free survival after 5 years, showing this therapy to be highly effective. An 11.5% drop-out rate after 3.5 months of therapy indicates the appropriateness of the MELD exception. Rigorous selection is important for the continued success of this treatment. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cancer risk screening surveillance primary sclerosing cholangitis primary sclerosing cholangitis psc rare chronic inflammatory condition mainly large bile ducts affecting predominantly young men associated presence inflammatory bowel disease known cure psc progresses cirrhosis death 10 20 years hepatobiliary malignancy especially cholangiocarcinoma feared complication associated poor overall survival screening surveillance appear improve overall outcomes capture many relevant studies broad search criteria employed within pubmed database given high prevalence ibd associations development malignancy two separate search strategies employed results filtered english language first search identified risks epidemiological factors surveillance strategies patients psc risk developing malignancy mesh terms included cholangitis sclerosing digestive system neoplasms liver neoplasms biliary tract neoplasms cholangiocarcinoma gallbladder neoplasms colonic neoplasms rectal neoplasms pancreatic neoplasms risk factors risk surveillance epidemiology screen second included inflammatory bowel diseases crohn colitis assessed additional malignancies lymphoma skin neoplasms total 288 results returned 21 duplicates 267 remaining abstracts assessed relevance inclusion authors patients psc show significantly higher average risk development hepatobiliary colonic malignancies including cholangiocarcinoma gallbladder carcinoma colorectal carcinoma yearly ultrasound surveillance followed definitive cross sectional imaging prudent arrive timely diagnosis carcinoma reducing morbidity mortality pubmed","probabilities":0.9799733,"Title":"Cancer risk, screening and surveillance in primary sclerosing cholangitis","Abstract":"Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory condition mainly of the large bile ducts, affecting predominantly young men, and is associated with the presence of inflammatory bowel disease. There is no known cure for PSC, which progresses to cirrhosis or death over 10-20 years. Hepatobiliary malignancy, especially cholangiocarcinoma, is a feared complication associated with poor overall survival. Screening and surveillance appear to improve overall outcomes. To capture as many relevant studies, broad search criteria were employed within the PubMed database. Given the high prevalence of IBD and its own associations with the development of malignancy two separate search strategies were employed. Results were filtered by English language. The first search identified the risks, epidemiological factors and surveillance strategies for patients with PSC at risk for developing malignancy. MeSH terms included: cholangitis, sclerosing, digestive system neoplasms, liver neoplasms, biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms, colonic neoplasms, rectal neoplasms, or pancreatic neoplasms, risk factors, risk, surveillance, epidemiology and screen. The second included inflammatory bowel diseases, Crohn's, or colitis, and assessed for additional malignancies such as lymphoma and skin neoplasms. A total of 288 results returned with 21 duplicates; 267 remaining abstracts were assessed for relevance for inclusion by the authors. Patients with PSC show significantly higher than average risk for the development of hepatobiliary and colonic malignancies including cholangiocarcinoma, gallbladder carcinoma and colorectal carcinoma. Yearly ultrasound surveillance followed with more definitive cross-sectional imaging is prudent to arrive in a timely diagnosis of carcinoma, reducing morbidity and mortality.","Source":"PubMed","category":"HUMAN","training_data":"Cancer risk, screening and surveillance in primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is a rare chronic inflammatory condition mainly of the large bile ducts, affecting predominantly young men, and is associated with the presence of inflammatory bowel disease. There is no known cure for PSC, which progresses to cirrhosis or death over 10-20 years. Hepatobiliary malignancy, especially cholangiocarcinoma, is a feared complication associated with poor overall survival. Screening and surveillance appear to improve overall outcomes. To capture as many relevant studies, broad search criteria were employed within the PubMed database. Given the high prevalence of IBD and its own associations with the development of malignancy two separate search strategies were employed. Results were filtered by English language. The first search identified the risks, epidemiological factors and surveillance strategies for patients with PSC at risk for developing malignancy. MeSH terms included: cholangitis, sclerosing, digestive system neoplasms, liver neoplasms, biliary tract neoplasms, cholangiocarcinoma, gallbladder neoplasms, colonic neoplasms, rectal neoplasms, or pancreatic neoplasms, risk factors, risk, surveillance, epidemiology and screen. The second included inflammatory bowel diseases, Crohn's, or colitis, and assessed for additional malignancies such as lymphoma and skin neoplasms. A total of 288 results returned with 21 duplicates; 267 remaining abstracts were assessed for relevance for inclusion by the authors. Patients with PSC show significantly higher than average risk for the development of hepatobiliary and colonic malignancies including cholangiocarcinoma, gallbladder carcinoma and colorectal carcinoma. Yearly ultrasound surveillance followed with more definitive cross-sectional imaging is prudent to arrive in a timely diagnosis of carcinoma, reducing morbidity and mortality. PubMed","prediction_labels":"HUMAN"},{"cleaned":"photodynamic therapy patients advanced hilar cholangiocarcinoma percutaneous cholangioscopic versus peroral transpapillary approach objective study aimed compare clinical outcomes patients advanced hilar cholangiocarcinoma cc underwent photodynamic therapy pdt either percutaneous transhepatic cholangioscopy ptcs endoscopic retrograde cholangiopancreatography ercp background data pdt proposed promising therapy treatment unresectable hilar cc resistant conventional standard treatment however studies compared delivery methods pdt unresectable hilar cc patients methods thirty seven adult patients advanced hilar cc included study twenty four patients treated ptcs directed pdt 13 patients treated ercp directed pdt analyzed retrospectively results ptcs ercp directed pdt groups comparable respect age gender health status pretreatment bilirubin levels bismuth type hilar cc stage length hospital stay differed significantly p 0 001 two groups median hospital stay 37 days range 13 77 days ercp directed pdt group versus 63 days range 23 125 days ptcs directed group ptcs directed pdt patients demonstrated overall survival similar ercp directed pdt patients median survival 11 6 versus 9 5 months respectively p 0 96 lower pre pdt bilirubin levels p 0 002 significant predictor improved survival patients underwent pdt determined multivariate analysis median metal stent patency similar groups ptcs directed pdt group n 8 6 2 months ercp directed pdt group n 7 7 2 months p 0 642 survival ptcs ercp directed pdt statistically different patients advanced hilar cc conclusions lower pre pdt bilirubin levels associated longer survival patients pubmed","probabilities":0.9799733,"Title":"Photodynamic Therapy in Patients with Advanced Hilar Cholangiocarcinoma: Percutaneous Cholangioscopic Versus Peroral Transpapillary Approach","Abstract":"OBJECTIVE: This study aimed to compare the clinical outcomes of patients with advanced hilar cholangiocarcinoma (CC) who underwent photodynamic therapy (PDT) with either percutaneous transhepatic cholangioscopy (PTCS) or endoscopic retrograde cholangiopancreatography (ERCP). BACKGROUND DATA: PDT has been proposed as a promising therapy for treatment of unresectable hilar CC that is resistant to conventional standard treatment. However, few studies have compared the delivery methods of PDT in unresectable hilar CC patients. METHODS: Thirty-seven adult patients with advanced hilar CC were included in this study. Twenty-four patients treated with PTCS-directed PDT and 13 patients treated with ERCP-directed PDT were analyzed retrospectively. RESULTS: The PTCS- and ERCP-directed PDT groups were comparable with respect to age, gender, health status, pretreatment bilirubin levels, Bismuth type, and hilar CC stage. The length of hospital stay differed significantly (p < 0.001) between the two groups, with a median hospital stay of 37 days (range, 13-77 days) in the ERCP-directed PDT group versus 63 days (range, 23-125 days) in the PTCS-directed group. PTCS-directed PDT patients demonstrated an overall survival similar to that of ERCP-directed PDT patients, with a median survival of 11.6 versus 9.5 months, respectively (p = 0.96). Only lower pre-PDT bilirubin levels (p = 0.002) were a significant predictor of improved survival in all patients who underwent PDT, as determined by multivariate analysis. Median metal stent patency was similar between the groups [PTCS-directed PDT group (n = 8), 6.2 months; ERCP-directed PDT group (n = 7), 7.2 months; p = 0.642]. Survival after PTCS- or ERCP-directed PDT was not statistically different in patients with advanced hilar CC. CONCLUSIONS: Lower pre-PDT bilirubin levels were associated with longer survival in all patients.","Source":"PubMed","category":"HUMAN","training_data":"Photodynamic Therapy in Patients with Advanced Hilar Cholangiocarcinoma: Percutaneous Cholangioscopic Versus Peroral Transpapillary Approach OBJECTIVE: This study aimed to compare the clinical outcomes of patients with advanced hilar cholangiocarcinoma (CC) who underwent photodynamic therapy (PDT) with either percutaneous transhepatic cholangioscopy (PTCS) or endoscopic retrograde cholangiopancreatography (ERCP). BACKGROUND DATA: PDT has been proposed as a promising therapy for treatment of unresectable hilar CC that is resistant to conventional standard treatment. However, few studies have compared the delivery methods of PDT in unresectable hilar CC patients. METHODS: Thirty-seven adult patients with advanced hilar CC were included in this study. Twenty-four patients treated with PTCS-directed PDT and 13 patients treated with ERCP-directed PDT were analyzed retrospectively. RESULTS: The PTCS- and ERCP-directed PDT groups were comparable with respect to age, gender, health status, pretreatment bilirubin levels, Bismuth type, and hilar CC stage. The length of hospital stay differed significantly (p < 0.001) between the two groups, with a median hospital stay of 37 days (range, 13-77 days) in the ERCP-directed PDT group versus 63 days (range, 23-125 days) in the PTCS-directed group. PTCS-directed PDT patients demonstrated an overall survival similar to that of ERCP-directed PDT patients, with a median survival of 11.6 versus 9.5 months, respectively (p = 0.96). Only lower pre-PDT bilirubin levels (p = 0.002) were a significant predictor of improved survival in all patients who underwent PDT, as determined by multivariate analysis. Median metal stent patency was similar between the groups [PTCS-directed PDT group (n = 8), 6.2 months; ERCP-directed PDT group (n = 7), 7.2 months; p = 0.642]. Survival after PTCS- or ERCP-directed PDT was not statistically different in patients with advanced hilar CC. CONCLUSIONS: Lower pre-PDT bilirubin levels were associated with longer survival in all patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"chromatin remodeling dna repair intrahepatic cholangiocarcinoma possible driver tumorigenesis background intrahepatic cholangiocarcinoma ihcc second common primary liver cancer poor survival poor response standard chemotherapy molecular mechanisms underlying tumorigenesis poorly understood reports idh1 2 kras mutations fgfr2 translocations herein investigate molecular landscape ihcc single tertiary care center design twelve cases selected dna extracted ffpe selection areas highest tumor content matched tumor normal tissue analyzed using customized panel targeting 580 exomes cancer related genes single nucleotide variation snv insertions deletions indels copy number variation cnv tumor mutational burden tmb using clinically validated pipeline results tested samples showed strikingly low tmb range 0 05 1 75 mutations per megabase flt4 atm nup98 lcg1 syne1 among commonly mutated genes altered snv indels 33 tested cases mutually exclusive ihd1 r132c mutation braf v600e mutation identified two separate cases her2 erbb2 amplification copy number 32 identified one case low tumor mutational burden google scholar","probabilities":0.875,"Title":"Chromatin Remodeling And Dna Repair In Intrahepatic Cholangiocarcinoma: A Possible Driver Of Tumorigenesis","Abstract":"Background: Intrahepatic cholangiocarcinoma (IHCC), the second most common primary liver cancer, has poor survival and a poor response to standard chemotherapy. Molecular mechanisms underlying tumorigenesis are poorly understood, with some reports of IDH1/2, KRAS mutations, and FGFR2 translocations. Herein, we investigate the molecular landscape of IHCC in a single tertiary care center. \nDesign: Twelve cases were selected. DNA was extracted from FFPE after selection of areas with highest tumor content. Matched tumor and normal tissue were analyzed using our customized panel targeting 580 exomes in cancer related genes for single nucleotide variation (SNV), insertions/deletions (InDels), copy number variation (CNV), and tumor mutational burden (TMB) using our clinically validated pipeline. \nResults: All of the tested samples showed a strikingly low TMB (range, 0.05 – 1.75 mutations per megabase). FLT4, ATM, NUP98, LCG1, and SYNE1 were among the most commonly mutated genes and were altered by SNV or indels in up to 33% of the tested cases. Mutually exclusive IHD1 R132C mutation and BRAF V600E mutation were identified in two separate cases. Her2/ERBB2 amplification (copy number = 32) was identified in one case with low tumor mutational burden.","Source":"Google Scholar","category":"ANIMAL","training_data":"Chromatin Remodeling And Dna Repair In Intrahepatic Cholangiocarcinoma: A Possible Driver Of Tumorigenesis Background: Intrahepatic cholangiocarcinoma (IHCC), the second most common primary liver cancer, has poor survival and a poor response to standard chemotherapy. Molecular mechanisms underlying tumorigenesis are poorly understood, with some reports of IDH1/2, KRAS mutations, and FGFR2 translocations. Herein, we investigate the molecular landscape of IHCC in a single tertiary care center. \nDesign: Twelve cases were selected. DNA was extracted from FFPE after selection of areas with highest tumor content. Matched tumor and normal tissue were analyzed using our customized panel targeting 580 exomes in cancer related genes for single nucleotide variation (SNV), insertions/deletions (InDels), copy number variation (CNV), and tumor mutational burden (TMB) using our clinically validated pipeline. \nResults: All of the tested samples showed a strikingly low TMB (range, 0.05 – 1.75 mutations per megabase). FLT4, ATM, NUP98, LCG1, and SYNE1 were among the most commonly mutated genes and were altered by SNV or indels in up to 33% of the tested cases. Mutually exclusive IHD1 R132C mutation and BRAF V600E mutation were identified in two separate cases. Her2/ERBB2 amplification (copy number = 32) was identified in one case with low tumor mutational burden. \n Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"anthropometric risk factors cancers biliary tract biliary tract cancers pooling project biliary tract cancers rare highly fatal poorly understood etiology identifying potentially modifiable risk factors cancers essential prevention estimated relationship adiposity cancer across biliary tract including cancers gallbladder gbc intrahepatic bile ducts ihbdc extrahepatic bile ducts ehbdc ampulla vater avc pooled data 27 prospective cohorts 2 7 million adults adiposity measured using baseline body mass index bmi waist circumference hip circumference waist hip waist height ratios hrs 95 confidence intervals 95 ci estimated using cox proportional hazards models adjusted sex education race smoking alcohol consumption age time metric baseline hazard stratified study 37 883 648 person years follow 1 343 gbc cases 1 194 ehbdc cases 784 ihbdc cases 623 avc cases occurred 5 kg m 2 increase bmi risk increases gbc hr 1 27 95 ci 1 19 1 36 ihbdc hr 1 32 95 ci 1 21 1 45 ehbdc hr 1 13 95 ci 1 03 1 23 avc hr 0 99 95 ci 0 88 1 11 increasing waist circumference hip circumference waist hip ratio waist height ratio associated gbc ihbdc ehbdc avc results indicate adult adiposity associated increased risk biliary tract cancer particularly gbc ihbdc moreover provide evidence recommending weight maintenance programs reduce risk developing cancers significance findings identify correlation adiposity biliary tract cancers indicating weight management programs may help minimize risk diseases pubmed","probabilities":0.9799733,"Title":"Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project","Abstract":"Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m(2) increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases.","Source":"PubMed","category":"HUMAN","training_data":"Anthropometric Risk Factors for Cancers of the Biliary Tract in the Biliary Tract Cancers Pooling Project Biliary tract cancers are rare but highly fatal with poorly understood etiology. Identifying potentially modifiable risk factors for these cancers is essential for prevention. Here we estimated the relationship between adiposity and cancer across the biliary tract, including cancers of the gallbladder (GBC), intrahepatic bile ducts (IHBDC), extrahepatic bile ducts (EHBDC), and the ampulla of Vater (AVC). We pooled data from 27 prospective cohorts with over 2.7 million adults. Adiposity was measured using baseline body mass index (BMI), waist circumference, hip circumference, waist-to-hip, and waist-to-height ratios. HRs and 95% confidence intervals (95% CI) were estimated using Cox proportional hazards models adjusted for sex, education, race, smoking, and alcohol consumption with age as the time metric and the baseline hazard stratified by study. During 37,883,648 person-years of follow-up, 1,343 GBC cases, 1,194 EHBDC cases, 784 IHBDC cases, and 623 AVC cases occurred. For each 5 kg/m(2) increase in BMI, there were risk increases for GBC (HR = 1.27; 95% CI, 1.19-1.36), IHBDC (HR = 1.32; 95% CI, 1.21-1.45), and EHBDC (HR = 1.13; 95% CI, 1.03-1.23), but not AVC (HR = 0.99; 95% CI, 0.88-1.11). Increasing waist circumference, hip circumference, waist-to-hip ratio, and waist-to-height ratio were associated with GBC and IHBDC but not EHBDC or AVC. These results indicate that adult adiposity is associated with an increased risk of biliary tract cancer, particularly GBC and IHBDC. Moreover, they provide evidence for recommending weight maintenance programs to reduce the risk of developing these cancers. SIGNIFICANCE: These findings identify a correlation between adiposity and biliary tract cancers, indicating that weight management programs may help minimize the risk of these diseases. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long noncoding rna component mitochondrial rna processing endoribonuclease involved progression cholangiocarcinoma regulating microrna 217 cholangiocarcinoma cca malignant tumor originating bile duct epithelium incidence increasing year year recent years long noncoding rnas lncrnas found play important role occurrence progression malignant tumors present study first time abnormal expression lnc rna component mitochondrial rna processing endoribonuclease rmrp possible role cca found explored effects rmrp various behaviors cca cells vitro vivo addition second generation sequencing explored microrna expression profiles rmrp may affect hccc 9810 cell line also validated explored role microrna 217 mir 217 high differential expression vitro experiments findings indicated rmrp play part promoting cancer regulating expression mir 217 rmrp involved progression cca novel indicator poor prognosis patients cca stn","probabilities":0.9467213,"Title":"Long Noncoding-Rna Component Of Mitochondrial Rna Processing Endoribonuclease Is Involved In The Progression Of Cholangiocarcinoma By Regulating Microrna-217","Abstract":"Cholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelium and its incidence is increasing year by year. In recent years, long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and progression of malignant tumors. In the present study, for the first time, abnormal expression of lnc-RNA component of mitochondrial RNA processing endoribonuclease (RMRP) and its possible role in CCA were found. We explored the effects of RMRP on various behaviors of CCA cells in vitro and in vivo. In addition, by second-generation sequencing, we explored the microRNA expression profiles that RMRP may affect in the HCCC-9810 cell line. We also validated and explored the role of microRNA-217 (miR-217) with high differential expression by in vitro experiments. Our findings indicated that RMRP can play a part in promoting cancer by regulating the expression of miR-217. RMRP is involved in the progression of CCA and can be a novel indicator of poor prognosis in patients with CCA.","Source":"STN","category":"ANIMAL","training_data":"Long Noncoding-Rna Component Of Mitochondrial Rna Processing Endoribonuclease Is Involved In The Progression Of Cholangiocarcinoma By Regulating Microrna-217 Cholangiocarcinoma (CCA) is a malignant tumor originating from bile duct epithelium and its incidence is increasing year by year. In recent years, long noncoding RNAs (lncRNAs) have been found to play an important role in the occurrence and progression of malignant tumors. In the present study, for the first time, abnormal expression of lnc-RNA component of mitochondrial RNA processing endoribonuclease (RMRP) and its possible role in CCA were found. We explored the effects of RMRP on various behaviors of CCA cells in vitro and in vivo. In addition, by second-generation sequencing, we explored the microRNA expression profiles that RMRP may affect in the HCCC-9810 cell line. We also validated and explored the role of microRNA-217 (miR-217) with high differential expression by in vitro experiments. Our findings indicated that RMRP can play a part in promoting cancer by regulating the expression of miR-217. RMRP is involved in the progression of CCA and can be a novel indicator of poor prognosis in patients with CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"glasgow prognostic score predicts therapeutic outcome pancreaticoduodenectomy carcinoma ampulla vater background systemic inflammation evidenced glasgow prognostic score gps predicts cancer specific survival various types cancer aim study evaluate significance gps therapeutic outcome pancreaticoduodenectomy carcinoma ampulla vater patients methods subjects study 30 patients underwent elective pancreaticoduodenectomy carcinoma ampulla vater assessment systemic inflammatory response using gps patients classified three groups patients normal albumin 3 5 g dl normal c reactive protein crp 1 0 mg dl gps 0 n 23 low albumin 3 5 g dl elevated crp 1 0 mg dl gps 1 n 5 low albumin 3 5 g dl elevated crp 1 0 mg dl gps 2 n 2 retrospectively investigated relationship patients characteristics including gps disease free survival well overall survival results disease free survival advanced tumor stage p 0 0401 advanced lymph node metastasis p 0 0001 preoperative biliary drainage p 0 0157 univariate analysis advanced lymph node metastasis p 0 0271 multivariate analysis significant independent predictors cancer recurrence overall survival univariate multivariate analyses advanced lymph node metastasis p 0 0006 p 0 0411 respectively gps 1 2 p 0 0034 p 0 0484 respectively significant independent predictors poor patient outcome conclusion gps patients carcinoma ampulla vater independent prognostic predictor elective pancreaticoduodenectomy pubmed","probabilities":0.9799733,"Title":"Glasgow prognostic score predicts therapeutic outcome after pancreaticoduodenectomy for carcinoma of the ampulla of vater","Abstract":"BACKGROUND: Systemic inflammation, as evidenced by the Glasgow prognostic score (GPS), predicts cancer-specific survival in various types of cancer. The aim of this study was to evaluate the significance of GPS on the therapeutic outcome after pancreaticoduodenectomy for carcinoma of the ampulla of Vater. PATIENTS AND METHODS: The subjects of this study were 30 patients who underwent elective pancreaticoduodenectomy for carcinoma of the ampulla of Vater. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: patients with normal albumin (≥ 3.5 g/dl) and normal C-reactive protein (CRP) (≤ 1.0 mg/dl) as GPS 0 (n=23), those with low albumin (<3.5 g/dl) or elevated CRP (>1.0 mg/dl) as GPS 1 (n=5), and those with low albumin (<3.5 g/dl) and elevated CRP (>1.0 mg/dl) as GPS 2 (n=2). We retrospectively investigated the relationship between patients' characteristics, including GPS, and disease-free survival, as well as overall survival. RESULTS: For disease-free survival, advanced tumor stage (p=0.0401), advanced lymph node metastasis (p<0.0001), and preoperative biliary drainage (p=0.0157) in univariate analysis, and advanced lymph node metastasis (p=0.0271) in multivariate analysis were significant and independent predictors of cancer recurrence. For overall survival, in both univariate and multivariate analyses, advanced lymph node metastasis (p=0.0006 and p=0.0411, respectively) and GPS 1 or 2 (p=0.0034 and p=0.0484, respectively) were significant and independent predictors of poor patient outcome. CONCLUSION: The GPS in patients with carcinoma of the ampulla of Vater is an independent prognostic predictor after elective pancreaticoduodenectomy.","Source":"PubMed","category":"HUMAN","training_data":"Glasgow prognostic score predicts therapeutic outcome after pancreaticoduodenectomy for carcinoma of the ampulla of vater BACKGROUND: Systemic inflammation, as evidenced by the Glasgow prognostic score (GPS), predicts cancer-specific survival in various types of cancer. The aim of this study was to evaluate the significance of GPS on the therapeutic outcome after pancreaticoduodenectomy for carcinoma of the ampulla of Vater. PATIENTS AND METHODS: The subjects of this study were 30 patients who underwent elective pancreaticoduodenectomy for carcinoma of the ampulla of Vater. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: patients with normal albumin (≥ 3.5 g/dl) and normal C-reactive protein (CRP) (≤ 1.0 mg/dl) as GPS 0 (n=23), those with low albumin (<3.5 g/dl) or elevated CRP (>1.0 mg/dl) as GPS 1 (n=5), and those with low albumin (<3.5 g/dl) and elevated CRP (>1.0 mg/dl) as GPS 2 (n=2). We retrospectively investigated the relationship between patients' characteristics, including GPS, and disease-free survival, as well as overall survival. RESULTS: For disease-free survival, advanced tumor stage (p=0.0401), advanced lymph node metastasis (p<0.0001), and preoperative biliary drainage (p=0.0157) in univariate analysis, and advanced lymph node metastasis (p=0.0271) in multivariate analysis were significant and independent predictors of cancer recurrence. For overall survival, in both univariate and multivariate analyses, advanced lymph node metastasis (p=0.0006 and p=0.0411, respectively) and GPS 1 or 2 (p=0.0034 and p=0.0484, respectively) were significant and independent predictors of poor patient outcome. CONCLUSION: The GPS in patients with carcinoma of the ampulla of Vater is an independent prognostic predictor after elective pancreaticoduodenectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma among offset colour proof printing workers exposed 12 dichloropropane dichloromethane objectives present study conducted investigate relationship occupational chemical exposure incidence cholangiocarcinoma among workers offset colour proof printing section small printing company osaka japan methods identified 51 men worked proof printing room 11 men worked front room least 1 year 1991 2006 interviewed chemicals used estimated levels exposure chemicals also investigated medical records 11 cholangiocarcinoma patients calculated standardised mortality ratio smr 1991 2011 results workers used 1 2 dichloropropane 1 2 dcp approximately 1985 2006 dichloromethane dcm approximately 1985 1997 1998 exposure concentrations estimated 100 670 ppm 1 2 dcp 80 540 ppm dcm among proof printing workers 11 patients pathologically diagnosed cholangiocarcinoma ages diagnosis 25 45 years ages death 27 46 years among six deceased individuals primary cancer site intrahepatic bile duct five patients extrahepatic bile ducts six patients exposed 1 2 dcp 7 17 years diagnosed cholangiocarcinoma 7 20 years first exposure ten patients also exposed dcm 1 13 years smr cholangiocarcinoma 2900 expected deaths 0 00204 95 ci 1100 6400 workers combined conclusions findings suggest 1 2 dcp dcm may cause cholangiocarcinoma humans stn","probabilities":0.9799733,"Title":"Cholangiocarcinoma Among Offset Colour Proof-Printing Workers Exposed To 12-Dichloropropane And/Or Dichloromethane","Abstract":"Objectives: The present study was conducted to investigate the relationship between occupational chemical exposure and incidence of cholangiocarcinoma among workers in the offset colour proof-printing section of a small printing company in Osaka, Japan. \r\n\r\n Methods: We identified 51 men who had worked in the proof-printing room, and 11 men who had worked in the front room for at least 1 year between 1991 and 2006. We interviewed them about the chemicals they used, and estimated their levels of exposure to chemicals. We also investigated the medical records of 11 cholangiocarcinoma patients, and calculated the standardised mortality ratio (SMR) from 1991 to 2011. \r\n\r\n Results: Workers used 1,2-dichloropropane (1,2-DCP) from approximately 1985 to 2006, and dichloromethane (DCM) from approximately 1985 to 1997/1998. Exposure concentrations were estimated to be 100-670 ppm for 1,2-DCP and 80-540 ppm for DCM among the proof-printing workers. All 11 patients were pathologically diagnosed with cholangiocarcinoma. Ages at diagnosis were 25-45 years, and ages at death were 27-46 years among the six deceased individuals. The primary cancer site was the intrahepatic bile duct for five patients, and the extrahepatic bile ducts for six. All patients were exposed to 1,2-DCP for 7-17 years and diagnosed with cholangiocarcinoma 7-20 years after their first exposure. Ten patients were also exposed to DCM for 1-13 years. The SMR for cholangiocarcinoma was 2900 (expected deaths: 0.00204, 95% CI 1100 to 6400) for all workers combined. \r\n\r\n Conclusions: These findings suggest that 1,2-DCP and/or DCM may cause cholangiocarcinoma in humans.","Source":"STN","category":"HUMAN","training_data":"Cholangiocarcinoma Among Offset Colour Proof-Printing Workers Exposed To 12-Dichloropropane And/Or Dichloromethane Objectives: The present study was conducted to investigate the relationship between occupational chemical exposure and incidence of cholangiocarcinoma among workers in the offset colour proof-printing section of a small printing company in Osaka, Japan. \r\n\r\n Methods: We identified 51 men who had worked in the proof-printing room, and 11 men who had worked in the front room for at least 1 year between 1991 and 2006. We interviewed them about the chemicals they used, and estimated their levels of exposure to chemicals. We also investigated the medical records of 11 cholangiocarcinoma patients, and calculated the standardised mortality ratio (SMR) from 1991 to 2011. \r\n\r\n Results: Workers used 1,2-dichloropropane (1,2-DCP) from approximately 1985 to 2006, and dichloromethane (DCM) from approximately 1985 to 1997/1998. Exposure concentrations were estimated to be 100-670 ppm for 1,2-DCP and 80-540 ppm for DCM among the proof-printing workers. All 11 patients were pathologically diagnosed with cholangiocarcinoma. Ages at diagnosis were 25-45 years, and ages at death were 27-46 years among the six deceased individuals. The primary cancer site was the intrahepatic bile duct for five patients, and the extrahepatic bile ducts for six. All patients were exposed to 1,2-DCP for 7-17 years and diagnosed with cholangiocarcinoma 7-20 years after their first exposure. Ten patients were also exposed to DCM for 1-13 years. The SMR for cholangiocarcinoma was 2900 (expected deaths: 0.00204, 95% CI 1100 to 6400) for all workers combined. \r\n\r\n Conclusions: These findings suggest that 1,2-DCP and/or DCM may cause cholangiocarcinoma in humans. STN","prediction_labels":"HUMAN"},{"cleaned":"targeting alpha133p53 isoform restore chemosensitivity 5 fluorouracil resistant cholangiocarcinoma cells lack normal p53 transactivation domain 133p53 isoform exhibits anti p53 function many studies report correlation 133p53 expression poor survival various cancers including cholangiocarcinoma cca cancer bile ducts cca almost always results short survival times relevance 133p53 drug resistance cca yet well understood study aimed demonstrate association 133p53 5 fluorouracil 5 fu resistance cca 133p53 protein highly expressed cca patients poor outcome compared favorable outcome statistically significant however significant correlation found normalized 133p53 levels 5 fu resistance defined ex vivo histoculture drug response assay p 0 019 two stable 5 fu resistant cca cell lines kku m139r ic50 38 8 m kku m214r ic50 39 5 m used model evaluate role 133p53 increased 133p53 correlated 5 fu dose dependent manner transient knockdown 133p53 expression restore drug sensitivity resistant cca cells 11 45 fold reduction ic50 compared control upon 133p53 silencing apoptotic signaling enhanced upregulation bax downregulation bcl 2 additionally p21 p27 upregulated resulting cell cycle arrest g2 inhibition colony formation prolong doubling time also observed findings demonstrated chemosensitivity modulated via targeting 133p53 suggesting potential use 133p53 candidate targeting therapy cca stn","probabilities":0.9467213,"Title":"Targeting The Alpha133P53 Isoform Can Restore Chemosensitivity In 5-Fluorouracil-Resistant Cholangiocarcinoma Cells","Abstract":"Lack of the normal p53 transactivation domain, ∆133p53 isoform exhibits anti-p53 function. Many studies report the correlation between ∆133p53 expression and poor survival in various cancers, including cholangiocarcinoma (CCA), which is a cancer of the bile ducts. CCA almost always results in short survival times. The relevance of ∆133p53 to drug resistance in CCA is not yet well understood. This study aimed to demonstrate the association between ∆133p53 and 5-fluorouracil (5-FU) resistance in CCA. ∆133p53 protein was highly expressed in CCA patients with poor outcome compared to favorable outcome but was not statistically significant. However, a significant correlation was found between normalized ∆133p53 levels and 5-FU resistance which was defined by an ex vivo histoculture drug response assay (P=0.019). Two stable 5-FU-resistant CCA cell lines, KKU-M139R (IC50 38.8 µM) and KKU-M214R (IC50 39.5 µM), were used as a model to evaluate the role of ∆133p53. Increased ∆133p53 was correlated with 5-FU in a dose-dependent manner. The transient knockdown of ∆133p53 expression can restore drug sensitivity in both resistant CCA cells with 11- to 45-fold reduction of IC50 compared to control. Upon ∆133p53 silencing, apoptotic signaling was enhanced by the upregulation of Bax and downregulation of Bcl-2. Additionally, p21 and p27 were upregulated, resulting in cell cycle arrest at G2. Inhibition of colony formation and prolong doubling time were also observed. Our findings demonstrated that chemosensitivity can be modulated via targeting of ∆133p53 suggesting the potential use of ∆133p53 as a candidate for targeting therapy in CCA.","Source":"STN","category":"ANIMAL","training_data":"Targeting The Alpha133P53 Isoform Can Restore Chemosensitivity In 5-Fluorouracil-Resistant Cholangiocarcinoma Cells Lack of the normal p53 transactivation domain, ∆133p53 isoform exhibits anti-p53 function. Many studies report the correlation between ∆133p53 expression and poor survival in various cancers, including cholangiocarcinoma (CCA), which is a cancer of the bile ducts. CCA almost always results in short survival times. The relevance of ∆133p53 to drug resistance in CCA is not yet well understood. This study aimed to demonstrate the association between ∆133p53 and 5-fluorouracil (5-FU) resistance in CCA. ∆133p53 protein was highly expressed in CCA patients with poor outcome compared to favorable outcome but was not statistically significant. However, a significant correlation was found between normalized ∆133p53 levels and 5-FU resistance which was defined by an ex vivo histoculture drug response assay (P=0.019). Two stable 5-FU-resistant CCA cell lines, KKU-M139R (IC50 38.8 µM) and KKU-M214R (IC50 39.5 µM), were used as a model to evaluate the role of ∆133p53. Increased ∆133p53 was correlated with 5-FU in a dose-dependent manner. The transient knockdown of ∆133p53 expression can restore drug sensitivity in both resistant CCA cells with 11- to 45-fold reduction of IC50 compared to control. Upon ∆133p53 silencing, apoptotic signaling was enhanced by the upregulation of Bax and downregulation of Bcl-2. Additionally, p21 and p27 were upregulated, resulting in cell cycle arrest at G2. Inhibition of colony formation and prolong doubling time were also observed. Our findings demonstrated that chemosensitivity can be modulated via targeting of ∆133p53 suggesting the potential use of ∆133p53 as a candidate for targeting therapy in CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"effect vascular endothelial growth factor c expression lymph node metastasis human cholangiocarcinoma present study aimed evaluate expression vascular endothelial growth factor c vegf c human cholangiocarcinoma tissues role metastasis vitro total 65 biopsy samples cholangiocarcinoma plus frh 0201 cell line investigated expression vegf c human cholangiocarcinoma specimens evaluated immunohistochemistry ihc effect vegf c tumor cell migration proliferation measured mtt transwell assays frh 0201 cell line according ihc results biopsies human cholangiocarcinoma stained positively vegf c positive rate 75 4 49 65 moreover vegf c expressed higher level patients lymph node metastasis without lymph node metastasis vitro vegf c exhibited marked growth stimulation concentration 5 ng ml able promote cholangiocarcinoma cell migration significantly findings suggested vegf c may useful factor predict lymph node metastasis cholangiocarcinoma tissues indicates vegf c plays significant role proliferation migration cholangiocarcinoma cells google scholar","probabilities":0.9467213,"Title":"Effect Of Vascular Endothelial Growth Factor-C Expression On Lymph Node Metastasis In Human Cholangiocarcinoma","Abstract":"The present study aimed to evaluate the expression of vascular endothelial growth factor C (VEGF‑C) in human cholangiocarcinoma tissues and its role in metastasis in vitro. A total of 65 biopsy samples of cholangiocarcinoma, plus the FRH‑0201 cell line, were investigated. The expression of VEGF‑C in the human cholangiocarcinoma specimens was evaluated by immunohistochemistry (IHC). The effect of VEGF‑C on tumor cell migration and proliferation was measured by MTT and Transwell assays in the FRH‑0201 cell line. According to the IHC results, the biopsies of human cholangiocarcinoma were stained positively for VEGF‑C, with a positive rate of 75.4% (49/65). Moreover, VEGF‑C was expressed at a higher level in the patients with lymph node metastasis than in those without lymph node metastasis. In vitro, VEGF‑C exhibited marked growth stimulation below the concentration of 5 ng/ml and was able to promote cholangiocarcinoma cell migration significantly. These findings suggested that VEGF‑C may be a useful factor to predict lymph node metastasis in cholangiocarcinoma tissues and indicates that VEGF‑C plays a significant role in proliferation and migration in cholangiocarcinoma cells.","Source":"Google Scholar","category":"ANIMAL","training_data":"Effect Of Vascular Endothelial Growth Factor-C Expression On Lymph Node Metastasis In Human Cholangiocarcinoma The present study aimed to evaluate the expression of vascular endothelial growth factor C (VEGF‑C) in human cholangiocarcinoma tissues and its role in metastasis in vitro. A total of 65 biopsy samples of cholangiocarcinoma, plus the FRH‑0201 cell line, were investigated. The expression of VEGF‑C in the human cholangiocarcinoma specimens was evaluated by immunohistochemistry (IHC). The effect of VEGF‑C on tumor cell migration and proliferation was measured by MTT and Transwell assays in the FRH‑0201 cell line. According to the IHC results, the biopsies of human cholangiocarcinoma were stained positively for VEGF‑C, with a positive rate of 75.4% (49/65). Moreover, VEGF‑C was expressed at a higher level in the patients with lymph node metastasis than in those without lymph node metastasis. In vitro, VEGF‑C exhibited marked growth stimulation below the concentration of 5 ng/ml and was able to promote cholangiocarcinoma cell migration significantly. These findings suggested that VEGF‑C may be a useful factor to predict lymph node metastasis in cholangiocarcinoma tissues and indicates that VEGF‑C plays a significant role in proliferation and migration in cholangiocarcinoma cells. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"prognostic evaluation mucin 5ac expression intrahepatic cholangiocarcinoma mass forming type following hepatectomy aim study aimed investigate clinicopathological predictors survival patients intrahepatic cholangiocarcinoma mass forming type icc mf following curative intent hepatectomy methods clinical characteristics outcomes analyzed series 42 patients underwent curative hepatectomy icc mf february 1987 december 2012 relationship immunohistochemical expression profiles mucin muc core proteins muc2 muc5ac muc6 surgical outcomes examined results overall median follow period 2 6 years 0 2 17 9 bile duct reconstruction p 0 017 lymph node metastasis p 0 049 maximal mass diameter 5 0 cm p 0 002 muc5ac expression p 0 003 identified significant adverse predictors overall survival univariate analysis bile duct reconstruction p 0 048 maximal mass diameter 5 0 cm p 0 002 muc5ac expression p 0 005 found independent predictors poor prognosis multivariate analysis maximal mass diameter 5 0 cm p 0 011 found independent predictor tumor recurrence strong correlation muc5ac expression lymph node metastasis p 0 021 muc6 expression frequent patients concurrent muc5ac expression p 0 019 conclusions muc5ac expression significantly related long term prognosis aggressive tumor development may useful prognostic marker pubmed","probabilities":0.9799733,"Title":"Prognostic evaluation of mucin-5AC expression in intrahepatic cholangiocarcinoma, mass-forming type, following hepatectomy","Abstract":"AIM: This study aimed to investigate the clinicopathological predictors of survival in patients with intrahepatic cholangiocarcinoma, mass-forming type (ICC-MF), following curative intent hepatectomy. METHODS: Clinical characteristics and outcomes were analyzed in a series of 42 patients who underwent curative hepatectomy for ICC-MF between February 1987 and December 2012. The relationship between immunohistochemical expression profiles of mucin (MUC) core proteins (MUC2, MUC5AC, and MUC6) and surgical outcomes was examined. RESULTS: The overall median follow-up period was 2.6 years (0.2-17.9). Bile duct reconstruction (p = 0.017), lymph node metastasis (p = 0.049), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.003) were identified as significant adverse predictors of overall survival by univariate analysis. Bile duct reconstruction (p = 0.048), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.005) were found to be independent predictors of poor prognosis by multivariate analysis. Maximal mass diameter ≥5.0 cm (p = 0.011) was found to be an independent predictor for the tumor recurrence. There was a strong correlation between MUC5AC expression and lymph node metastasis (p = 0.021). MUC6 expression was more frequent in patients with concurrent MUC5AC expression (p = 0.019). CONCLUSIONS: MUC5AC expression was significantly related to long-term prognosis and aggressive tumor development, and may be a useful prognostic marker.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic evaluation of mucin-5AC expression in intrahepatic cholangiocarcinoma, mass-forming type, following hepatectomy AIM: This study aimed to investigate the clinicopathological predictors of survival in patients with intrahepatic cholangiocarcinoma, mass-forming type (ICC-MF), following curative intent hepatectomy. METHODS: Clinical characteristics and outcomes were analyzed in a series of 42 patients who underwent curative hepatectomy for ICC-MF between February 1987 and December 2012. The relationship between immunohistochemical expression profiles of mucin (MUC) core proteins (MUC2, MUC5AC, and MUC6) and surgical outcomes was examined. RESULTS: The overall median follow-up period was 2.6 years (0.2-17.9). Bile duct reconstruction (p = 0.017), lymph node metastasis (p = 0.049), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.003) were identified as significant adverse predictors of overall survival by univariate analysis. Bile duct reconstruction (p = 0.048), maximal mass diameter ≥5.0 cm (p = 0.002), and MUC5AC expression (p = 0.005) were found to be independent predictors of poor prognosis by multivariate analysis. Maximal mass diameter ≥5.0 cm (p = 0.011) was found to be an independent predictor for the tumor recurrence. There was a strong correlation between MUC5AC expression and lymph node metastasis (p = 0.021). MUC6 expression was more frequent in patients with concurrent MUC5AC expression (p = 0.019). CONCLUSIONS: MUC5AC expression was significantly related to long-term prognosis and aggressive tumor development, and may be a useful prognostic marker. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparative study clinicopathological significance birc7 stc2 expression squamous cell adenosquamous carcinomas adenocarcinoma gallbladder gallbladder cancers gbcs uncommon highly aggressive cancers majority gbcs adenocarcinomas acs rare subtypes gbcs squamous cell carcinoma sc adenosquamous carcinoma asc observed well clinicopathological characteristics sc asc well documented expressions birc7 stc2 observed tumors however birc7 stc2 expressions clinical significances gallbladder cancer reported study protein expressions birc7 stc2 46 scs ascs 80 acs measured using immunohistochemistry demonstrated positive birc7 stc2 expressions significantly associated large tumor mass 3cm high tnm stage lymph node metastasis sc asc ac p 0 05 positive expression birc7 significantly associated invasion around tissues organs sc asc ac additionally negative birc7 stc2 expressions significantly associated surgical curability ac univariate kaplan meier analysis showed birc7 stc2 expressions differentiation tumor size tnm stages invasion lymph node metastasis surgical curability significantly associated post operative survival sc asc ac patients p 0 001 multivariate cox regression analysis showed positive birc7 stc2 expressions independent poor prognostic factors sc asc ac patients study suggested positive birc7 stc2 expressions closely correlated clinical pathological biological behaviors well poor prognosis gallbladder cancer pubmed","probabilities":0.962963,"Title":"Comparative study of clinicopathological significance, BIRC7, and STC2 expression between squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder","Abstract":"Gallbladder cancers (GBCs) are uncommon, but highly aggressive cancers. The majority of GBCs are adenocarcinomas (ACs), but rare subtypes of GBCs such as squamous cell carcinoma (SC) and adenosquamous carcinoma (ASC) are observed as well. The clinicopathological characteristics of SC/ASC have not been well documented. Expressions of BIRC7 and STC2 were observed in some tumors. However, BIRC7 and STC2 expressions and clinical significances in gallbladder cancer have not been reported.In this study, the protein expressions of BIRC7 and STC2 in 46 SCs/ASCs and 80 ACs were measured using immunohistochemistry. We demonstrated that positive BIRC7 and STC2 expressions were significantly associated with large tumor mass (>3cm), high TNM stage and lymph node metastasis in SC/ASC and AC (p<0.05). Positive expression of BIRC7 was significantly associated with invasion of around tissues and organs in both SC/ASC and AC. Additionally, negative BIRC7 and STC2 expressions were significantly associated with surgical curability in AC. Univariate Kaplan-Meier analysis showed that BIRC7 and STC2 expressions, differentiation, tumor size, TNM stages, invasion, lymph node metastasis, and surgical curability were significantly associated with post-operative survival in both SC/ASC and AC patients(p < 0.001). Multivariate Cox regression analysis showed that positive BIRC7 and STC2 expressions are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive BIRC7 and STC2 expressions are closely correlated with clinical, pathological, and biological behaviors as well as poor-prognosis of gallbladder cancer.","Source":"PubMed","category":"HUMAN","training_data":"Comparative study of clinicopathological significance, BIRC7, and STC2 expression between squamous cell/adenosquamous carcinomas and adenocarcinoma of gallbladder Gallbladder cancers (GBCs) are uncommon, but highly aggressive cancers. The majority of GBCs are adenocarcinomas (ACs), but rare subtypes of GBCs such as squamous cell carcinoma (SC) and adenosquamous carcinoma (ASC) are observed as well. The clinicopathological characteristics of SC/ASC have not been well documented. Expressions of BIRC7 and STC2 were observed in some tumors. However, BIRC7 and STC2 expressions and clinical significances in gallbladder cancer have not been reported.In this study, the protein expressions of BIRC7 and STC2 in 46 SCs/ASCs and 80 ACs were measured using immunohistochemistry. We demonstrated that positive BIRC7 and STC2 expressions were significantly associated with large tumor mass (>3cm), high TNM stage and lymph node metastasis in SC/ASC and AC (p<0.05). Positive expression of BIRC7 was significantly associated with invasion of around tissues and organs in both SC/ASC and AC. Additionally, negative BIRC7 and STC2 expressions were significantly associated with surgical curability in AC. Univariate Kaplan-Meier analysis showed that BIRC7 and STC2 expressions, differentiation, tumor size, TNM stages, invasion, lymph node metastasis, and surgical curability were significantly associated with post-operative survival in both SC/ASC and AC patients(p < 0.001). Multivariate Cox regression analysis showed that positive BIRC7 and STC2 expressions are independent poor-prognostic factors in both SC/ASC and AC patients. Our study suggested that positive BIRC7 and STC2 expressions are closely correlated with clinical, pathological, and biological behaviors as well as poor-prognosis of gallbladder cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"histopathology based immunoscore predicts recurrence intrahepatic cholangiocarcinoma hepatectomy intrahepatic cholangiocarcinoma icc rare malignancy poor prognosis evaluation recurrence risk liver resection great importance iccs aimed assess prognostic value intra peritumoral immune infiltrations establish novel histopathology related immunoscore hri associated icc recurrence total 280 icc patients received curative resection february 2005 july 2011 enrolled study patients randomly assigned derivation cohort n 176 validation cohort n 104 sixteen immune biomarkers intra peritumoral tissues examined immunohistochemistry least absolute shrinkage selection operator lasso cox model used establish hri score cox regression analysis used multivariate analysis nine recurrence related immune features identified integrated hri score hri score used categorize patients low risk high risk groups using x tile software kaplan meier analysis presented hri score showed good stratification low risk high risk groups derivation cohort p 0 001 validation cohort p 0 014 respectively multivariate analysis demonstrated serum glutamyl transpeptidase carbohydrate antigen 19 9 lymphoid metastasis tumor numbers hri score independent risk factors associated recurrence free survival rfs combination shen model hri score provided better performance recurrence prediction compared traditional staging systems hri score might serve promising rfs predictor icc prognostic values pubmed","probabilities":0.88235295,"Title":"Histopathology-based immunoscore predicts recurrence for intrahepatic cholangiocarcinoma after hepatectomy","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with poor prognosis. The evaluation of recurrence risk after liver resection is of great importance for ICCs. We aimed to assess the prognostic value of intra- and peritumoral immune infiltrations and to establish a novel histopathology-related immunoscore (HRI) associated with ICC recurrence. A total of 280 ICC patients who received curative resection between February 2005 and July 2011 were enrolled in our study. Patients were randomly assigned to the derivation cohort (n = 176) or the validation cohort (n = 104). Sixteen immune biomarkers in both intra- and peritumoral tissues were examined by immunohistochemistry. The least absolute shrinkage and selection operator (LASSO) Cox model was used to establish the HRI score. Cox regression analysis was used for multivariate analysis. Nine recurrence-related immune features were identified and integrated into the HRI score. The HRI score was used to categorize patients into low-risk and high-risk groups using the X-tile software. Kaplan-Meier analysis presented that the HRI score showed good stratification between low-risk and high-risk groups in both the derivation cohort (P < 0.001) and the validation cohort (P = 0.014), respectively. Multivariate analysis demonstrated that serum γ-glutamyl transpeptidase, carbohydrate antigen 19-9, lymphoid metastasis, tumor numbers, and the HRI score were independent risk factors associated with recurrence-free survival (RFS). The combination of Shen's model and HRI score provided better performance in recurrence prediction compared with traditional staging systems. The HRI score might serve as a promising RFS predictor for ICC with prognostic values.","Source":"PubMed","category":"HUMAN","training_data":"Histopathology-based immunoscore predicts recurrence for intrahepatic cholangiocarcinoma after hepatectomy Intrahepatic cholangiocarcinoma (ICC) is a rare malignancy with poor prognosis. The evaluation of recurrence risk after liver resection is of great importance for ICCs. We aimed to assess the prognostic value of intra- and peritumoral immune infiltrations and to establish a novel histopathology-related immunoscore (HRI) associated with ICC recurrence. A total of 280 ICC patients who received curative resection between February 2005 and July 2011 were enrolled in our study. Patients were randomly assigned to the derivation cohort (n = 176) or the validation cohort (n = 104). Sixteen immune biomarkers in both intra- and peritumoral tissues were examined by immunohistochemistry. The least absolute shrinkage and selection operator (LASSO) Cox model was used to establish the HRI score. Cox regression analysis was used for multivariate analysis. Nine recurrence-related immune features were identified and integrated into the HRI score. The HRI score was used to categorize patients into low-risk and high-risk groups using the X-tile software. Kaplan-Meier analysis presented that the HRI score showed good stratification between low-risk and high-risk groups in both the derivation cohort (P < 0.001) and the validation cohort (P = 0.014), respectively. Multivariate analysis demonstrated that serum γ-glutamyl transpeptidase, carbohydrate antigen 19-9, lymphoid metastasis, tumor numbers, and the HRI score were independent risk factors associated with recurrence-free survival (RFS). The combination of Shen's model and HRI score provided better performance in recurrence prediction compared with traditional staging systems. The HRI score might serve as a promising RFS predictor for ICC with prognostic values. PubMed","prediction_labels":"HUMAN"},{"cleaned":"value lymph node dissection patients intrahepatic cholangiocarcinom underwent hepetectomy impact long term survival background surgical resection shown improve long term survival patients intrahepatic cholangiocarcinoma icc benefit lymph node dissection still controversial aims study investigate prognostic factors icc examine impact lymph node metastasis extent lymph node dissection survival materials methods total 64 patients icc operated curative intent resultant macroscopic curative resection r0 r1 patients classified according extent lymph node dissection clinicopathological characteristics survival reviewed retrospectively results patients underwent anatomical resection 5 year survival rates 39 5 multivariate analysis revealed lymph node metastasis hazard ratio 3 317 independent prognostic factors survival recurrence occurred 41 patients median disease free survival time 12 3 months tumor differentiation independent prognostic factor disease free survival hazard ratio 3 158 extent lymph node dissection affect occurrence complication regional alpha lymph node dissection group demonstrated similar survival lymph node sampling group although significant high incidence lymph node metastases observed regional alpha lymph node dissection group extent lymph node dissection affect survival patients without lymph node involvement conclusions regional alpha lymph node dissection enhanced survival icc patients lymph node metastasis exact nodal status confirmed lymph node dissection pericholedochal lymph nodes stn","probabilities":0.9799733,"Title":"Value Of Lymph Node Dissection In Patients With Intrahepatic Cholangiocarcinom Underwent Hepetectomy-Impact On Long Term Survival","Abstract":"Background: Surgical resection has been shown to improve long-term survival for patients with intrahepatic cholangiocarcinoma (ICC). The benefit of lymph node dissection is still controversial. The aims of this study were to investigate the prognostic factors of ICC and to examine the impact of lymph node metastasis and extent of lymph node dissection on survival. \r\n\r\n Materials and methods: A total of 64 patients with ICC were operated on with curative intent and resultant macroscopic curative resection (R0 and R1). The patients were classified according to the extent of the lymph node dissection. Clinicopathological characteristics and survival were reviewed retrospectively. \r\n\r\n Results: All patients underwent anatomical resection. The 5-year survival rates were 39.5%. Multivariate analysis revealed that lymph node metastasis (hazard ratio: 3.317) was an independent prognostic factors on survival. Recurrence occurred in 41 patients. Median disease-free survival time was 12.3 months. Tumor differentiation was an independent prognostic factor for disease-free survival (hazard ratio: 3.158). The extent of lymph node dissection did not affect the occurrence of complication. Regional+alpha lymph node dissection group demonstrated similar survival to those of lymph node sampling group, although significant high incidence of lymph node metastases was observed in the regional+alpha lymph node dissection group. The extent of lymph node dissection did not affect the survival in the patients without lymph node involvement. \r\n\r\n Conclusions: The regional+alpha lymph node dissection enhanced the survival in the ICC patients with lymph node metastasis, and the exact nodal status could be confirmed by lymph node dissection in the pericholedochal lymph nodes.","Source":"STN","category":"HUMAN","training_data":"Value Of Lymph Node Dissection In Patients With Intrahepatic Cholangiocarcinom Underwent Hepetectomy-Impact On Long Term Survival Background: Surgical resection has been shown to improve long-term survival for patients with intrahepatic cholangiocarcinoma (ICC). The benefit of lymph node dissection is still controversial. The aims of this study were to investigate the prognostic factors of ICC and to examine the impact of lymph node metastasis and extent of lymph node dissection on survival. \r\n\r\n Materials and methods: A total of 64 patients with ICC were operated on with curative intent and resultant macroscopic curative resection (R0 and R1). The patients were classified according to the extent of the lymph node dissection. Clinicopathological characteristics and survival were reviewed retrospectively. \r\n\r\n Results: All patients underwent anatomical resection. The 5-year survival rates were 39.5%. Multivariate analysis revealed that lymph node metastasis (hazard ratio: 3.317) was an independent prognostic factors on survival. Recurrence occurred in 41 patients. Median disease-free survival time was 12.3 months. Tumor differentiation was an independent prognostic factor for disease-free survival (hazard ratio: 3.158). The extent of lymph node dissection did not affect the occurrence of complication. Regional+alpha lymph node dissection group demonstrated similar survival to those of lymph node sampling group, although significant high incidence of lymph node metastases was observed in the regional+alpha lymph node dissection group. The extent of lymph node dissection did not affect the survival in the patients without lymph node involvement. \r\n\r\n Conclusions: The regional+alpha lymph node dissection enhanced the survival in the ICC patients with lymph node metastasis, and the exact nodal status could be confirmed by lymph node dissection in the pericholedochal lymph nodes. STN","prediction_labels":"HUMAN"},{"cleaned":"upregulation gastric adenocarcinoma predictive long intergenic non coding rna promotes progression predicts poor prognosis perihilar cholangiocarcinoma perihilar cholangiocarcinoma phcc one aggressive complex types cancer poor survival despite advances phcc diagnosis treatment biology tumor remains poorly understood recent studies suggested long non coding rnas lncrnas crucial determinants cancer progression however role lncrnas phcc rarely reported function gastric adenocarcinoma predictive long intergenic non coding rna gaplinc phcc yet elucidated present study observed significant upregulation gaplinc phcc cell lines clinical specimens p 0 05 furthermore comparing clinicopathological characteristics expression data high gaplinc expression revealed associated stage p 0 013 n stage p 0 001 tumor node metastasis stage p 0 001 phcc furthermore kaplan meier analysis demonstrated gaplinc expression associated poor overall survival progression free survival rates phcc furthermore univariate multivariate cox regression analyses identified high gaplinc expression risk factor poor prognosis phcc gaplinc upregulation promoted migration invasion phcc cells transwell matrigel assays respectively gaplinc deficiency inhibited phcc cell metastasis furthermore phcc cells gaplinc overexpression exhibited markedly increased proliferation ability cell counting kit 8 assay however gaplinc interference significantly suppressed cell proliferation conclusion gaplinc may promote phcc progression may serve potential prognostic marker therapeutic target phcc stn","probabilities":0.9467213,"Title":"Upregulation Of Gastric Adenocarcinoma Predictive Long Intergenic Non Coding Rna Promotes Progression And Predicts Poor Prognosis In Perihilar Cholangiocarcinoma","Abstract":"Perihilar cholangiocarcinoma (PHCC) is one of the most aggressive and complex types of cancer with a poor survival. Despite advances in PHCC diagnosis and treatment, the biology of this tumor remains poorly understood. Recent studies have suggested long non-coding RNAs (lncRNAs) as crucial determinants of cancer progression. However, the role of lncRNAs in PHCC is rarely reported and the function of gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in PHCC has yet to be elucidated. The present study observed a significant upregulation of GAPLINC in PHCC cell lines and clinical specimens (P<0.05). Furthermore, by comparing clinicopathological characteristics with expression data, high GAPLINC expression was revealed to be associated with the T stage (P=0.013), N stage (P<0.001) and Tumor-Node-Metastasis stage (P<0.001) of PHCC. Furthermore, Kaplan-Meier analysis demonstrated that GAPLINC expression was associated with poor overall survival and progression-free survival rates in PHCC. Furthermore, univariate and multivariate COX regression analyses identified high GAPLINC expression as a risk factor of a poor prognosis in PHCC. GAPLINC upregulation promoted the migration and invasion of PHCC cells in Transwell and Matrigel assays, respectively, while GAPLINC deficiency inhibited PHCC cell metastasis. Furthermore, PHCC cells with GAPLINC overexpression exhibited markedly increased proliferation ability in a Cell Counting kit-8 assay. However, GAPLINC interference significantly suppressed cell proliferation. In conclusion, GAPLINC may promote PHCC progression and may serve as a potential prognostic marker and therapeutic target of PHCC.","Source":"STN","category":"ANIMAL","training_data":"Upregulation Of Gastric Adenocarcinoma Predictive Long Intergenic Non Coding Rna Promotes Progression And Predicts Poor Prognosis In Perihilar Cholangiocarcinoma Perihilar cholangiocarcinoma (PHCC) is one of the most aggressive and complex types of cancer with a poor survival. Despite advances in PHCC diagnosis and treatment, the biology of this tumor remains poorly understood. Recent studies have suggested long non-coding RNAs (lncRNAs) as crucial determinants of cancer progression. However, the role of lncRNAs in PHCC is rarely reported and the function of gastric adenocarcinoma predictive long intergenic non-coding RNA (GAPLINC) in PHCC has yet to be elucidated. The present study observed a significant upregulation of GAPLINC in PHCC cell lines and clinical specimens (P<0.05). Furthermore, by comparing clinicopathological characteristics with expression data, high GAPLINC expression was revealed to be associated with the T stage (P=0.013), N stage (P<0.001) and Tumor-Node-Metastasis stage (P<0.001) of PHCC. Furthermore, Kaplan-Meier analysis demonstrated that GAPLINC expression was associated with poor overall survival and progression-free survival rates in PHCC. Furthermore, univariate and multivariate COX regression analyses identified high GAPLINC expression as a risk factor of a poor prognosis in PHCC. GAPLINC upregulation promoted the migration and invasion of PHCC cells in Transwell and Matrigel assays, respectively, while GAPLINC deficiency inhibited PHCC cell metastasis. Furthermore, PHCC cells with GAPLINC overexpression exhibited markedly increased proliferation ability in a Cell Counting kit-8 assay. However, GAPLINC interference significantly suppressed cell proliferation. In conclusion, GAPLINC may promote PHCC progression and may serve as a potential prognostic marker and therapeutic target of PHCC. STN","prediction_labels":"ANIMAL"},{"cleaned":"dyskerin expression human fetal adult neoplastic intrahepatic bile ducts correlations cholangiocarcinoma aggressiveness aims investigate immunohistochemical expression dyskerin biomarker involved ribosome production telomere maintenance human fetal adult neoplastic bile ducts possible correlations cholangiocarcinoma aggressiveness methods results sixty consecutive intrahepatic cholangiocarcinomas collected used tissue microarray construction total 176 cores clinical data follow also collected five fetal 10 normal adult livers included controls automated immunohistochemistry dyskerin p53 ki67 nucleolar silver staining performed normal livers dyskerin expression negative smaller bile ducts mean 44 8 m positive bile ducts larger diameter mean 116 1 m p 0 001 expression positive 56 7 cholangiocarcinomas correlated p53 mutation p 0 008 higher proliferative ki67 index p 0 003 included markers tumour aggressiveness finally dyskerin positive cholangiocarcinomas showed negative trend disease free survival p 0 078 univariate analysis conclusions non neoplastic biliary tree seems progressively lose dyskerin expression major branches peripheral portal bile ducts similarly intrahepatic cholangiocarcinomas showed two patterns dyskerin expression dyskerin positive phenotype seemed characterize aggressive cholangiocarcinomas stn","probabilities":1.0,"Title":"Dyskerin Expression In Human Fetal Adult And Neoplastic Intrahepatic Bile Ducts: Correlations With Cholangiocarcinoma Aggressiveness","Abstract":"Aims: To investigate the immunohistochemical expression of dyskerin, a biomarker involved in ribosome production and telomere maintenance, in human fetal, adult and neoplastic bile ducts, and possible correlations with cholangiocarcinoma aggressiveness. \r\n\r\n Methods and results: Sixty consecutive intrahepatic cholangiocarcinomas were collected and used for tissue microarray construction (total: 176 cores); clinical data and follow-up were also collected. Five fetal and 10 normal adult livers were included as controls. Automated immunohistochemistry for dyskerin, p53, and Ki67, and nucleolar silver staining, were performed. In normal livers, dyskerin expression was negative in smaller bile ducts (mean 44.8 μm) and positive in bile ducts of larger diameter (mean 116.1 μm; P < 0.001). Expression was positive in 56.7% of cholangiocarcinomas, and correlated with p53 mutation (P = 0.008) and a higher proliferative (Ki67) index (P = 0.003), which were included as markers of tumour aggressiveness. Finally, dyskerin-positive cholangiocarcinomas showed a negative trend in disease-free survival (P = 0.078) on univariate analysis. \r\n\r\n Conclusions: The non-neoplastic biliary tree seems to progressively lose dyskerin expression from the major branches to the peripheral portal bile ducts. Similarly, intrahepatic cholangiocarcinomas showed two patterns of dyskerin expression, and the dyskerin-positive phenotype seemed to characterize more aggressive cholangiocarcinomas.","Source":"STN","category":"ANIMAL","training_data":"Dyskerin Expression In Human Fetal Adult And Neoplastic Intrahepatic Bile Ducts: Correlations With Cholangiocarcinoma Aggressiveness Aims: To investigate the immunohistochemical expression of dyskerin, a biomarker involved in ribosome production and telomere maintenance, in human fetal, adult and neoplastic bile ducts, and possible correlations with cholangiocarcinoma aggressiveness. \r\n\r\n Methods and results: Sixty consecutive intrahepatic cholangiocarcinomas were collected and used for tissue microarray construction (total: 176 cores); clinical data and follow-up were also collected. Five fetal and 10 normal adult livers were included as controls. Automated immunohistochemistry for dyskerin, p53, and Ki67, and nucleolar silver staining, were performed. In normal livers, dyskerin expression was negative in smaller bile ducts (mean 44.8 μm) and positive in bile ducts of larger diameter (mean 116.1 μm; P < 0.001). Expression was positive in 56.7% of cholangiocarcinomas, and correlated with p53 mutation (P = 0.008) and a higher proliferative (Ki67) index (P = 0.003), which were included as markers of tumour aggressiveness. Finally, dyskerin-positive cholangiocarcinomas showed a negative trend in disease-free survival (P = 0.078) on univariate analysis. \r\n\r\n Conclusions: The non-neoplastic biliary tree seems to progressively lose dyskerin expression from the major branches to the peripheral portal bile ducts. Similarly, intrahepatic cholangiocarcinomas showed two patterns of dyskerin expression, and the dyskerin-positive phenotype seemed to characterize more aggressive cholangiocarcinomas. STN","prediction_labels":"ANIMAL"},{"cleaned":"long noncoding rna neat1 upregulates survivin facilitates gallbladder cancer progression sponging microrna 335 background gallbladder cancer gbc common cancer biliary tract molecularly targeted therapies available gbc loss microrna mir 335 expression may useful predictor clinical outcomes reversal loss expression may useful treatment strategy gbc study investigated whether long noncoding rna nuclear paraspeckle assembly transcript 1 neat1 sponges mir 335 gbc cells materials methods quantitative reverse transcription polymerase chain reaction qrt pcr western blotting immunohistochemistry used determine expression mir 335 neat1 survivin ki67 gbc cell lines gbc sd sgc 996 tissue samples patients n 25 cell counting kit 8 colony formation transwell migration invasion assays performed measure cell proliferation migration invasion bioinformatic analysis dual luciferase reporter assays utilized analyze correlativity results mir 335 overexpression resulted inhibition gbc cell proliferation invasion addition knockdown neat1 resulted downregulation survivin expression neat1 competitively sponges mir 335 neat1 knockdown resulted inhibited gbc cell proliferation invasion vitro gbc tumor growth vivo furthermore neat1 found upregulated gbc samples expression inversely correlated mir 335 levels positively correlated survivin levels conclusion findings indicate neat1 promotes survivin expression functioning competitive endogenous rna mir 335 gbc cells thus identified potential biomarker target gbc diagnosis therapy stn","probabilities":0.9467213,"Title":"Long Noncoding Rna Neat1 Upregulates Survivin And Facilitates Gallbladder Cancer Progression By Sponging Microrna-335","Abstract":"Background: Gallbladder cancer (GBC) is the most common cancer of the biliary tract, but molecularly targeted therapies are not available for GBC. Loss of microRNA (miR)-335 expression may be a useful predictor of clinical outcomes and the reversal of its loss of expression may be a useful treatment strategy for GBC. In this study, we investigated whether a long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) sponges miR-335 in GBC cells. \r\n\r\n Materials and methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to determine the expression of miR-335; NEAT1; survivin; and Ki67 in GBC cell lines (GBC-SD and SGC-996) and tissue samples from patients (n = 25). Cell Counting Kit-8, colony-formation, and Transwell migration and invasion assays were performed to measure cell proliferation, migration, and invasion. Bioinformatic analysis and dual-luciferase reporter assays were utilized to analyze correlativity. \r\n\r\n Results: miR-335 overexpression resulted in inhibition of GBC cell proliferation and invasion. In addition, knockdown of NEAT1 resulted in downregulation of survivin expression. As NEAT1 competitively \"sponges\" miR-335, NEAT1 knockdown resulted in inhibited GBC cell proliferation and invasion in vitro and GBC tumor growth in vivo. Furthermore, NEAT1 was found to be upregulated in GBC samples, and its expression was inversely correlated with miR-335 levels, but positively correlated with survivin levels. \r\n\r\n Conclusion: These findings indicate that NEAT1 promotes survivin expression by functioning as a competitive endogenous RNA for miR-335 in GBC cells; thus, we have identified a potential biomarker and target for GBC diagnosis and therapy.","Source":"STN","category":"ANIMAL","training_data":"Long Noncoding Rna Neat1 Upregulates Survivin And Facilitates Gallbladder Cancer Progression By Sponging Microrna-335 Background: Gallbladder cancer (GBC) is the most common cancer of the biliary tract, but molecularly targeted therapies are not available for GBC. Loss of microRNA (miR)-335 expression may be a useful predictor of clinical outcomes and the reversal of its loss of expression may be a useful treatment strategy for GBC. In this study, we investigated whether a long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) sponges miR-335 in GBC cells. \r\n\r\n Materials and methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), Western blotting, and immunohistochemistry were used to determine the expression of miR-335; NEAT1; survivin; and Ki67 in GBC cell lines (GBC-SD and SGC-996) and tissue samples from patients (n = 25). Cell Counting Kit-8, colony-formation, and Transwell migration and invasion assays were performed to measure cell proliferation, migration, and invasion. Bioinformatic analysis and dual-luciferase reporter assays were utilized to analyze correlativity. \r\n\r\n Results: miR-335 overexpression resulted in inhibition of GBC cell proliferation and invasion. In addition, knockdown of NEAT1 resulted in downregulation of survivin expression. As NEAT1 competitively \"sponges\" miR-335, NEAT1 knockdown resulted in inhibited GBC cell proliferation and invasion in vitro and GBC tumor growth in vivo. Furthermore, NEAT1 was found to be upregulated in GBC samples, and its expression was inversely correlated with miR-335 levels, but positively correlated with survivin levels. \r\n\r\n Conclusion: These findings indicate that NEAT1 promotes survivin expression by functioning as a competitive endogenous RNA for miR-335 in GBC cells; thus, we have identified a potential biomarker and target for GBC diagnosis and therapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"differential expression e cadherin catenin s100a4 intestinal type nonintestinal type ampulla vater cancers background aims epithelial mesenchymal transition emt related proteins may exhibit differential expression intestinal type pancreatobiliary type ampulla vater carcinomas avcs evaluated expression e cadherin catenin s100a4 intestinal nonintestinal type avcs analyzed relationships clinicopathological variables survival methods clinicopathological review 105 patients avcs immunohistochemical staining e cadherin catenin s100a4 performed association clinicopathological parameters histological type expression emt proteins effects survival analyzed results sixty five intestinal type 35 pancreatobiliary type five types avcs identified severity emt changes differed avc types membranous loss e cadherin catenin observed nonintestinal type tumors whereas aberrant nonmembranous catenin expression observed intestinal type tumors emt related changes pronounced invasive tumor margin tumor center emt related changes related tumor aggressiveness among clinicopathological parameters desmoplastic reaction related overall survival reaction severe nonintestinal type intestinal type avcs conclusions dysregulation e cadherin cadherin s100a4 expression may play role carcinogenesis tumor progression avcs pubmed","probabilities":0.9799733,"Title":"Differential expression of E-cadherin, β-catenin, and S100A4 in intestinal type and nonintestinal type ampulla of Vater cancers","Abstract":"BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, β-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. METHODS: A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, β-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. RESULTS: Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and β-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous β-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. CONCLUSIONS: Dysregulation of E-cadherin, β-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs.","Source":"PubMed","category":"HUMAN","training_data":"Differential expression of E-cadherin, β-catenin, and S100A4 in intestinal type and nonintestinal type ampulla of Vater cancers BACKGROUND/AIMS: Epithelial-mesenchymal transition (EMT)-related proteins may exhibit differential expression in intestinal type or pancreatobiliary type ampulla of Vater carcinomas (AVCs). We evaluated the expression of E-cadherin, β-catenin, and S100A4 in intestinal and nonintestinal type AVCs and analyzed their relationships with clinicopathological variables and survival. METHODS: A clinicopathological review of 105 patients with AVCs and immunohistochemical staining for E-cadherin, β-catenin, and S100A4 were performed. The association between clinicopathological parameters, histological type, and expression of EMT proteins and their effects on survival were analyzed. RESULTS: Sixty-five intestinal type, 35 pancreatobiliary type, and five other types of AVCs were identified. The severity of EMT changes differed between the AVC types; membranous loss of E-cadherin and β-catenin was observed in nonintestinal type tumors, whereas aberrant nonmembranous β-catenin expression was observed in intestinal type tumors. EMT-related changes were more pronounced in the invasive tumor margin than in the tumor center, and these EMT-related changes were related to tumor aggressiveness. Among the clinicopathological parameters, a desmoplastic reaction was related to overall survival, and the reaction was more severe in nonintestinal type than in intestinal type AVCs. CONCLUSIONS: Dysregulation of E-cadherin, β-cadherin, and S100A4 expression may play a role in the carcinogenesis and tumor progression of AVCs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcomes left trisectionectomy right hepatectomy perihilar cholangiocarcinoma background right hepatectomy rh standard surgical procedure perihilar cholangiocarcinoma phc right sided predominance many centers although left trisectionectomy lt aggressively performed phc left sided predominance high volume centers surgical survival outcomes lt unclear therefore study aimed compare outcomes lt rh phc methods consecutive patients underwent surgical resection phc chiba university hospital 2008 2016 retrospectively reviewed outcomes patients phc underwent lt compared underwent rh following one one propensity score matching results 171 consecutive phc resection patients 111 eligible study 41 37 underwent lt 70 63 underwent rh matched cohort lt n 27 rh n 27 major complication rates 67 vs 52 p 0 42 90 day mortality rates 15 vs 0 p 0 11 r0 resection rates 56 vs 44 p 0 58 similar groups 3 year recurrence free survival rates 27 vs 47 p 0 27 overall survival rates 45 vs 60 p 0 17 also similar groups conclusions patients phc lt achieve similar surgical survival outcomes rh pubmed","probabilities":0.9799733,"Title":"Outcomes of left trisectionectomy and right hepatectomy for perihilar cholangiocarcinoma","Abstract":"BACKGROUND: Right hepatectomy (RH) is the standard surgical procedure for perihilar cholangiocarcinoma (PHC) with right-sided predominance in many centers. Although left trisectionectomy (LT) is aggressively performed for PHC with left-sided predominance in high-volume centers, the surgical and survival outcomes of LT are unclear. Therefore, this study aimed to compare the outcomes of LT and RH for PHC. METHODS: Consecutive patients who underwent surgical resection for PHC at Chiba University Hospital from 2008 to 2016 were retrospectively reviewed. The outcomes of patients with PHC who underwent LT were compared with those who underwent RH following one-to-one propensity score matching. RESULTS: Of 171 consecutive PHC resection patients, 111 were eligible for the study; 41 (37%) underwent LT, and 70 (63%) underwent RH. In a matched cohort (LT: n = 27, RH: n = 27), major complication rates (67% vs. 52%; p = 0.42), 90-day mortality rates (15% vs. 0%; p = 0.11) and R0 resection rates (56% vs. 44%; p = 0.58) were similar in both groups. The 3-year recurrence-free survival rates (27% vs. 47%; p = 0.27) and overall survival rates (45% vs. 60%; p = 0.17) were also similar in both groups. CONCLUSIONS: In patients with PHC, LT could achieve similar surgical and survival outcomes as RH.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes of left trisectionectomy and right hepatectomy for perihilar cholangiocarcinoma BACKGROUND: Right hepatectomy (RH) is the standard surgical procedure for perihilar cholangiocarcinoma (PHC) with right-sided predominance in many centers. Although left trisectionectomy (LT) is aggressively performed for PHC with left-sided predominance in high-volume centers, the surgical and survival outcomes of LT are unclear. Therefore, this study aimed to compare the outcomes of LT and RH for PHC. METHODS: Consecutive patients who underwent surgical resection for PHC at Chiba University Hospital from 2008 to 2016 were retrospectively reviewed. The outcomes of patients with PHC who underwent LT were compared with those who underwent RH following one-to-one propensity score matching. RESULTS: Of 171 consecutive PHC resection patients, 111 were eligible for the study; 41 (37%) underwent LT, and 70 (63%) underwent RH. In a matched cohort (LT: n = 27, RH: n = 27), major complication rates (67% vs. 52%; p = 0.42), 90-day mortality rates (15% vs. 0%; p = 0.11) and R0 resection rates (56% vs. 44%; p = 0.58) were similar in both groups. The 3-year recurrence-free survival rates (27% vs. 47%; p = 0.27) and overall survival rates (45% vs. 60%; p = 0.17) were also similar in both groups. CONCLUSIONS: In patients with PHC, LT could achieve similar surgical and survival outcomes as RH. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact vascular endothelial growth factor expression resected gallbladder carcinoma purpose study evaluate value vascular endothelial growth factor vegf expression confirmed prognostic factors predicting clinical outcomes resection gallbladder carcinoma gbc january 1999 january 2006 total 84 consecutive non selected patients underwent resection gbc retrospectively reviewed 84 patients studied 45 cases 53 6 exhibited high expression vegf placed high expression group 14 cases 16 7 showed vegf expression 25 cases 29 7 lower vegf levels pooled low expression group 46 4 relationship vegf status pm stage p 0 027 well histologic differentiation p 0 001 univariate analysis log rank test ecog performance status ca 19 9 pn stage pm stage histologic differentiation vegf expression significant prognostic factors p 0 015 0 001 0 020 0 001 0 040 0 001 respectively multivariate analysis revealed pn status vegf expression maintained independent prognostic influence overall survival p 0 001 p 0 013 respectively vegf expression positive correlation pm stage histologic differentiation pn status vegf expression independent prognostic factors overall survival patients resected gbc pubmed","probabilities":0.9799733,"Title":"Prognostic impact of vascular endothelial growth factor-A expression in resected gallbladder carcinoma","Abstract":"The purpose of this study was to evaluate the value of vascular endothelial growth factor-A (VEGF-A) expression and other confirmed prognostic factors in predicting clinical outcomes after the resection of gallbladder carcinoma (GBC). Between January 1999 and January 2006, a total of 84 consecutive and non-selected patients who underwent resection for GBC were retrospectively reviewed. Of the 84 patients studied, 45 cases (53.6%) exhibited high expression of VEGF-A and were placed into the high expression group. The 14 cases (16.7%) that showed no VEGF expression and the 25 cases (29.7%) that had lower VEGF-A levels were pooled into the low expression group (46.4%). There was a relationship between VEGF-A status and pM stage (P = 0.027) as well as histologic differentiation (P < 0.001). In univariate analysis by log-rank test, ECOG performance status, CA 19-9, pN stage, pM stage, histologic differentiation, and VEGF-A expression were significant prognostic factors (P = 0.015, 0.001, 0.020, <0.001, 0.040, and <0.001, respectively). Multivariate analysis revealed that pN status and VEGF-A expression maintained independent prognostic influence on overall survival (P < 0.001 and P = 0.013, respectively). VEGF-A expression has a positive correlation with pM stage and histologic differentiation. pN status and VEGF-A expression were independent prognostic factors of overall survival in patients with resected GBC.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic impact of vascular endothelial growth factor-A expression in resected gallbladder carcinoma The purpose of this study was to evaluate the value of vascular endothelial growth factor-A (VEGF-A) expression and other confirmed prognostic factors in predicting clinical outcomes after the resection of gallbladder carcinoma (GBC). Between January 1999 and January 2006, a total of 84 consecutive and non-selected patients who underwent resection for GBC were retrospectively reviewed. Of the 84 patients studied, 45 cases (53.6%) exhibited high expression of VEGF-A and were placed into the high expression group. The 14 cases (16.7%) that showed no VEGF expression and the 25 cases (29.7%) that had lower VEGF-A levels were pooled into the low expression group (46.4%). There was a relationship between VEGF-A status and pM stage (P = 0.027) as well as histologic differentiation (P < 0.001). In univariate analysis by log-rank test, ECOG performance status, CA 19-9, pN stage, pM stage, histologic differentiation, and VEGF-A expression were significant prognostic factors (P = 0.015, 0.001, 0.020, <0.001, 0.040, and <0.001, respectively). Multivariate analysis revealed that pN status and VEGF-A expression maintained independent prognostic influence on overall survival (P < 0.001 and P = 0.013, respectively). VEGF-A expression has a positive correlation with pM stage and histologic differentiation. pN status and VEGF-A expression were independent prognostic factors of overall survival in patients with resected GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"race intrahepatic cholangiocarcinoma disparities management survival abstract available google scholar","probabilities":0.9799733,"Title":"Race And Intrahepatic Cholangiocarcinoma: Disparities In Management And Survival","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Race And Intrahepatic Cholangiocarcinoma: Disparities In Management And Survival Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"human equilibrative nucleoside transporter 1 hent1 expression predictive biomarker gemcitabine chemotherapy biliary tract cancer gemcitabine principal chemotherapeutic agent biliary tract cancer btc expression human equilibrative nucleoside transporter 1 hent1 regarded potential predictive biomarker gemcitabine response cancers study conducted investigate association hent1 expression effects gemcitabine btc cell lines patients advanced btc receiving gemcitabine based chemotherapy total four btc cell lines hucct1 snu 478 snu 1079 snu 1196 tested mrna protein expression levels hent1 measured quantitative reverse transcription polymerase chain reaction western blotting respectively cell viability gemcitabine treatment measured chemosensitivity assay clinical assessment 40 patients unresectable recurrent btc treated gemcitabine 1000 mg m2 cisplatin 25 mg m2 june 2012 may 2014 enrolled among four cell lines snu1196 showed highest mrna protein levels hent1 expression hent1 showed linear correlation log value half maximal inhibitory concentration gemcitabine incubation gemcitabine pretreatment hent1 specific small interfering rna sirna resulted higher cell viability samples pretreated control sirna clinical evaluation median progression free survival 24 11 weeks among patients strong weak intratumoral hent1 immunohistochemical staining p 0 05 median overall survival 52 26 weeks p 0 15 respectively conclusion study showed increased hent1 expression associated stronger toxic effect gemcitabine btc cell lines clinical outcomes study suggest increased intratumoral hent1 immunohistochemical staining possible biomarker predicting better therapeutic effects gemcitabine patients advanced btc studies needed determine precise role hent1 btc google scholar","probabilities":0.9467213,"Title":"Human Equilibrative Nucleoside Transporter 1 (Hent1) Expression As A Predictive Biomarker For Gemcitabine Chemotherapy In Biliary Tract Cancer","Abstract":"Gemcitabine is a principal chemotherapeutic agent for biliary tract cancer (BTC). Expression of human equilibrative nucleoside transporter 1 (hENT1) is regarded as a potential predictive biomarker for a gemcitabine response in some cancers. This study was conducted to investigate the association between hENT1 expression and the effects of gemcitabine on BTC cell lines and on patients with advanced BTC receiving gemcitabine-based chemotherapy. A total of four BTC cell lines, HuCCT1, SNU-478, SNU-1079, and SNU-1196, were tested. mRNA and protein expression levels of hENT1 were measured by quantitative reverse-transcription polymerase chain reaction and western blotting, respectively. Cell viability after gemcitabine treatment was measured in a chemosensitivity assay. For clinical assessment, 40 patients with unresectable or recurrent BTC who were treated with gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) between June 2012 and May 2014 were enrolled. Among the four cell lines, SNU1196 showed the highest mRNA and protein levels of hENT1. Expression of hENT1 showed a linear correlation with the log value of the half-maximal inhibitory concentration of gemcitabine. During incubation with gemcitabine, pretreatment with hENT1-specific small interfering RNA (siRNA) resulted in higher cell viability than that in samples pretreated with control siRNA. In a clinical evaluation, the median progression-free survival was 24 and 11 weeks among patients with strong and weak intratumoral hENT1 immunohistochemical staining (P = 0.05), and the median overall survival was 52 and 26 weeks (P = 0.15), respectively. In conclusion, this study showed that increased hENT1 expression is associated with a stronger toxic effect of gemcitabine on BTC cell lines. The clinical outcomes in this study suggest that increased intratumoral hENT1 immunohistochemical staining is a possible biomarker predicting better therapeutic effects of gemcitabine on patients with advanced BTC. Further studies are needed to determine the precise role of hENT1 in BTC.","Source":"Google Scholar","category":"HUMAN","training_data":"Human Equilibrative Nucleoside Transporter 1 (Hent1) Expression As A Predictive Biomarker For Gemcitabine Chemotherapy In Biliary Tract Cancer Gemcitabine is a principal chemotherapeutic agent for biliary tract cancer (BTC). Expression of human equilibrative nucleoside transporter 1 (hENT1) is regarded as a potential predictive biomarker for a gemcitabine response in some cancers. This study was conducted to investigate the association between hENT1 expression and the effects of gemcitabine on BTC cell lines and on patients with advanced BTC receiving gemcitabine-based chemotherapy. A total of four BTC cell lines, HuCCT1, SNU-478, SNU-1079, and SNU-1196, were tested. mRNA and protein expression levels of hENT1 were measured by quantitative reverse-transcription polymerase chain reaction and western blotting, respectively. Cell viability after gemcitabine treatment was measured in a chemosensitivity assay. For clinical assessment, 40 patients with unresectable or recurrent BTC who were treated with gemcitabine (1000 mg/m2) and cisplatin (25 mg/m2) between June 2012 and May 2014 were enrolled. Among the four cell lines, SNU1196 showed the highest mRNA and protein levels of hENT1. Expression of hENT1 showed a linear correlation with the log value of the half-maximal inhibitory concentration of gemcitabine. During incubation with gemcitabine, pretreatment with hENT1-specific small interfering RNA (siRNA) resulted in higher cell viability than that in samples pretreated with control siRNA. In a clinical evaluation, the median progression-free survival was 24 and 11 weeks among patients with strong and weak intratumoral hENT1 immunohistochemical staining (P = 0.05), and the median overall survival was 52 and 26 weeks (P = 0.15), respectively. In conclusion, this study showed that increased hENT1 expression is associated with a stronger toxic effect of gemcitabine on BTC cell lines. The clinical outcomes in this study suggest that increased intratumoral hENT1 immunohistochemical staining is a possible biomarker predicting better therapeutic effects of gemcitabine on patients with advanced BTC. Further studies are needed to determine the precise role of hENT1 in BTC. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"pleural dissemination cholangiocarcinoma caused percutaneous transhepatic biliary drainage management resectable cholangiocarcinoma background 3 case reports addressed pleural dissemination association percutaneous transhepatic biliary drainage aim study investigate recurrence resection cholangiocarcinoma percutaneous transhepatic biliary drainage clarify incidence factors responsible pleural dissemination methods 2001 2015 reviewed retrospectively consecutive patients underwent resection perihilar distal cholangiocarcinoma percutaneous transhepatic biliary drainage recurrence including pleural dissemination results study period consecutive patients underwent resection cholangiocarcinoma management percutaneous transhepatic biliary drainage 100 patients 32 1 underwent left sided percutaneous transhepatic biliary drainage alone 212 67 9 underwent right sided percutaneous transhepatic biliary drainage without left sided percutaneous transhepatic biliary drainage pleural dissemination developed exclusively right side thoracic cavity resection found 12 patients 3 8 patients underwent right sided percutaneous transhepatic biliary drainage computed tomography demonstrated percutaneous transhepatic biliary drainage catheter passed thoracic cavity 12 patients diagnosis pleural dissemination made median 381 days range 44 2 944 days operation survival poor median survival time 516 days statistically right sided percutaneous transhepatic biliary drainage identified risk factor pleural dissemination conclusion pleural dissemination right sided percutaneous transhepatic biliary drainage likely procedure related iatrogenic complication special route percutaneous transhepatic biliary drainage catheter must passed right thoracic cavity pubmed","probabilities":0.9799733,"Title":"Pleural dissemination of cholangiocarcinoma caused by percutaneous transhepatic biliary drainage during the management of resectable cholangiocarcinoma","Abstract":"BACKGROUND: Only 3 case reports have addressed pleural dissemination in association with percutaneous transhepatic biliary drainage. The aim of this study was to investigate recurrence after resection of cholangiocarcinoma after percutaneous transhepatic biliary drainage and to clarify the incidence of and the factors responsible for pleural dissemination. METHODS: Between 2001 and 2015, we reviewed retrospectively all consecutive patients who underwent resection for perihilar or distal cholangiocarcinoma after percutaneous transhepatic biliary drainage for recurrence, including pleural dissemination. RESULTS: During the study period, all consecutive patients underwent resection of cholangiocarcinoma after management with percutaneous transhepatic biliary drainage. Of these, 100 patients (32.1%) underwent left-sided percutaneous transhepatic biliary drainage alone, and 212 (67.9%) underwent right-sided percutaneous transhepatic biliary drainage with or without left-sided percutaneous transhepatic biliary drainage. Pleural dissemination, which developed exclusively on the right side of the thoracic cavity after resection, was found in 12 patients (3.8%); these patients underwent right-sided percutaneous transhepatic biliary drainage; computed tomography demonstrated that the percutaneous transhepatic biliary drainage catheter passed through the thoracic cavity in all 12 patients. The diagnosis of pleural dissemination was made at a median of 381 days (range, 44 to 2,944 days) after operation. Survival was poor, with a median survival time of 516 days. Statistically, right-sided percutaneous transhepatic biliary drainage was identified as a risk factor for pleural dissemination. CONCLUSION: Pleural dissemination after right-sided percutaneous transhepatic biliary drainage is likely a procedure-related iatrogenic complication because of the \"special route\" by which the percutaneous transhepatic biliary drainage catheter must be passed through the right thoracic cavity.","Source":"PubMed","category":"HUMAN","training_data":"Pleural dissemination of cholangiocarcinoma caused by percutaneous transhepatic biliary drainage during the management of resectable cholangiocarcinoma BACKGROUND: Only 3 case reports have addressed pleural dissemination in association with percutaneous transhepatic biliary drainage. The aim of this study was to investigate recurrence after resection of cholangiocarcinoma after percutaneous transhepatic biliary drainage and to clarify the incidence of and the factors responsible for pleural dissemination. METHODS: Between 2001 and 2015, we reviewed retrospectively all consecutive patients who underwent resection for perihilar or distal cholangiocarcinoma after percutaneous transhepatic biliary drainage for recurrence, including pleural dissemination. RESULTS: During the study period, all consecutive patients underwent resection of cholangiocarcinoma after management with percutaneous transhepatic biliary drainage. Of these, 100 patients (32.1%) underwent left-sided percutaneous transhepatic biliary drainage alone, and 212 (67.9%) underwent right-sided percutaneous transhepatic biliary drainage with or without left-sided percutaneous transhepatic biliary drainage. Pleural dissemination, which developed exclusively on the right side of the thoracic cavity after resection, was found in 12 patients (3.8%); these patients underwent right-sided percutaneous transhepatic biliary drainage; computed tomography demonstrated that the percutaneous transhepatic biliary drainage catheter passed through the thoracic cavity in all 12 patients. The diagnosis of pleural dissemination was made at a median of 381 days (range, 44 to 2,944 days) after operation. Survival was poor, with a median survival time of 516 days. Statistically, right-sided percutaneous transhepatic biliary drainage was identified as a risk factor for pleural dissemination. CONCLUSION: Pleural dissemination after right-sided percutaneous transhepatic biliary drainage is likely a procedure-related iatrogenic complication because of the \"special route\" by which the percutaneous transhepatic biliary drainage catheter must be passed through the right thoracic cavity. PubMed","prediction_labels":"HUMAN"},{"cleaned":"biliary tract malignancies population based study incidence prognosis management patients background biliary tract malignancies uncommon population based studies available methods nationwide population based study iceland included patients diagnosed intra extrahepatic cholangiocarcinoma gallbladder ampullary cancer 1984 2012 patients identified icelandic cancer registry clinical information obtained patient records results overall 245 patients identified 38 intrahepatic cholangiocarcinoma 66 extrahepatic cholangiocarcinoma 73 gallbladder cancer gbc 68 ampullary cancer overall incidence bile tract malignancies 1 3 per 100 000 person years less 1 sub type overall bile tract malignancies males increased 1 3 95 ci 0 8 1 8 2 5 1 9 3 1 per 100 000 inhabitants incidence gbc among females decreased 1 1 0 7 1 5 0 5 0 2 0 7 surgery decreased extrahepatic cholangiocarcinoma 56 23 p 027 ampullary cancer 80 48 p 03 overall bile tract cancer 61 32 p 0001 use chemotherapy increased 4 32 p 0001 five year relative survival rates men 15 24 women significant improvement found survival conclusions overall incidence bile tract malignancies increased males gbc decreased women long term survival poor improve despite changes treatment stn","probabilities":0.9799733,"Title":"Biliary Tract Malignancies: A Population-Based Study On Incidence Prognosis And Management Of Patients","Abstract":"Background: Biliary tract malignancies are uncommon and few population-based studies are available. \r\n\r\n Methods: This nationwide population-based study in Iceland included all patients diagnosed with intra- and extrahepatic cholangiocarcinoma, gallbladder and ampullary cancer from 1984 to 2012. Patients were identified through the Icelandic Cancer Registry. Clinical information was obtained from patient records. \r\n\r\n Results: Overall 245 patients were identified: 38 had intrahepatic cholangiocarcinoma, 66 extrahepatic cholangiocarcinoma, 73 gallbladder cancer (GBC) and 68 ampullary cancer. Overall incidence for bile tract malignancies was 1-3 per 100,000 person-years and less than 1 by sub-type. The overall bile tract malignancies in males increased from 1.3 (95% CI 0.8-1.8) to 2.5 (1.9-3.1) per 100,000 inhabitants. The incidence of GBC among females decreased from 1.1 (0.7-1.5) to 0.5 (0.2-0.7). Surgery decreased for extrahepatic cholangiocarcinoma (56 to 23%, p = .027), ampullary cancer (80 to 48%, p = .03) and overall bile tract cancer (61 to 32%, p < .0001) but use of chemotherapy increased (4 to 32%, p < .0001). Five-year relative survival rates for men were 15% and 24% for women. No significant improvement was found in survival. \r\n\r\n Conclusions: Overall incidence of bile tract malignancies increased in males and GBC decreased in women. Long-term survival is poor and did not improve despite changes in treatment.","Source":"STN","category":"HUMAN","training_data":"Biliary Tract Malignancies: A Population-Based Study On Incidence Prognosis And Management Of Patients Background: Biliary tract malignancies are uncommon and few population-based studies are available. \r\n\r\n Methods: This nationwide population-based study in Iceland included all patients diagnosed with intra- and extrahepatic cholangiocarcinoma, gallbladder and ampullary cancer from 1984 to 2012. Patients were identified through the Icelandic Cancer Registry. Clinical information was obtained from patient records. \r\n\r\n Results: Overall 245 patients were identified: 38 had intrahepatic cholangiocarcinoma, 66 extrahepatic cholangiocarcinoma, 73 gallbladder cancer (GBC) and 68 ampullary cancer. Overall incidence for bile tract malignancies was 1-3 per 100,000 person-years and less than 1 by sub-type. The overall bile tract malignancies in males increased from 1.3 (95% CI 0.8-1.8) to 2.5 (1.9-3.1) per 100,000 inhabitants. The incidence of GBC among females decreased from 1.1 (0.7-1.5) to 0.5 (0.2-0.7). Surgery decreased for extrahepatic cholangiocarcinoma (56 to 23%, p = .027), ampullary cancer (80 to 48%, p = .03) and overall bile tract cancer (61 to 32%, p < .0001) but use of chemotherapy increased (4 to 32%, p < .0001). Five-year relative survival rates for men were 15% and 24% for women. No significant improvement was found in survival. \r\n\r\n Conclusions: Overall incidence of bile tract malignancies increased in males and GBC decreased in women. Long-term survival is poor and did not improve despite changes in treatment. STN","prediction_labels":"HUMAN"},{"cleaned":"autophagy may early event stepwise carcinogenesis via biliary intraepithelial neoplasia cholangiocarcinoma associated hepatolithiasis ackgrounds aims similar pancreatic intraepithelial neoplasia panin pancreatic carcinoma sequence model chol angiocarcinoma also reported follow stepwise carcino genesis process arise precursor lesion biliary intraepithelial neoplasia bilin previously disclosed cellular senescence participates cholangiocarcinogen esis large bile duct via bilin overexpression ezh2 plays role bypass escape senescence followed development overt carcinoma accumulating data suggest autophagy play important role occur rence development carcinomas autophagy pre cedes cellular senescence examined whether autophagy may involved multistep carcinogenesis cholangio carcinoma associated hepatolithiasis methods thirty five cases hepatolithiasis associated bilin chol angiocarcinoma 7 intrahepatic cholangiocarcinoma 8 intraductal papillary neoplasm bile duct ipnb 6 control livers surveyed lesions categorized following invasive carcinoma n 16 ipnb n 8 biln 3 n 16 bilin 1 2 n 41 normal large bile duct lbd n 56 peribiliary gland pbg n 54 examined immu nohistochemical expressions autophagy related proteins microtubule associated proteins light chain 3 lc3 beclin 1 p62 sequestosome 1 p62 extent expression semiquantitatively assessed using scores 0 3 posi tive cells 0 5 1 5 30 2 30 70 3 70 results expression lc3 cytoplasmic vesicular beclin 1 cyto plasmic p62 cytoplasmic nuclear significantly high bilin 1 2 compared lbd pbg p 0 01 expression lc3 beclin 1 p62 also significantly high bilin 3 ipnb invasive carcinoma p 0 05 com pared lbd pbg significant difference expression autophagy related proteins lbd pbg cases without hepatolithiasis conclusion study firstly disclosed expression autophagy re lated proteins lc3 beclin 1 p62 upregulated early stage bilin 1 2 multistep carcinogenesis cholangiocarcinoma associated hepatolithiasis autoph agy may involved occurrence development cholangiocarcinoma google scholar","probabilities":0.9799733,"Title":"Autophagy May Be An Early Event In The Stepwise Carcinogenesis Via Biliary Intraepithelial Neoplasia In Cholangiocarcinoma Associated With Hepatolithiasis","Abstract":"ackgrounds/Aims. Similar to the pancreatic intraepithelial neoplasia (PanIN)-pancreatic carcinoma sequence model, chol-angiocarcinoma is also reported to follow a stepwise carcino-genesis process and arise from the precursor lesion biliary intraepithelial neoplasia (BilIN). We have previously disclosed that cellular senescence participates in cholangiocarcinogen-esis in the large bile duct via BilIN and the overexpression of EZH2 plays a role in the bypass/escape from senescence followed by the development of overt carcinoma. Accumulating data suggest that autophagy play an important role in occur-rence and development of carcinomas and that autophagy pre-cedes cellular senescence. We examined whether autophagy may be involved in the multistep carcinogenesis in cholangio-carcinoma associated with hepatolithiasis. Methods. Thirty-five cases of hepatolithiasis associated with BilIN and /or chol-angiocarcinoma, 7 of intrahepatic cholangiocarcinoma, 8 of intraductal papillary neoplasm of the bile duct (IPNB) and 6 control livers were surveyed and lesions were categorized into the following: invasive carcinoma (n=16), IPNB (n=8), BIlN-3 (n=16), BilIN-1/2 (n=41), normal large bile duct (LBD, n=56) and peribiliary gland (PBG, n=54). We examined the immu-nohistochemical expressions of autophagy related proteins, microtubule-associated proteins-light chain 3β (LC3), Beclin-1 and p62/sequestosome-1 (p62). The extent of expression was semiquantitatively assessed using scores 0 to 3 (% of posi-tive cells, 0, <5%; 1, 5-30%; 2, 30-70%; 3, >70%). Results. The expression of LC3 (cytoplasmic, vesicular), Beclin-1 (cyto-plasmic) and p62 (cytoplasmic and nuclear) was significantly high in BilIN-1/2, compared to LBD and PBG (p<0.01). The expression of LC3, Beclin-1 and p62 was also significantly high in BilIN-3, IPNB and invasive carcinoma (p<0.05), com-pared to LBD and PBG. There was no significant difference in the expression of autophagy-related proteins in LBD and PBG between cases with and without hepatolithiasis. In conclusion, this study firstly disclosed that the expression of autophagy-re-lated proteins, LC3, Beclin-1 and p62, was upregulated at the early stage, BilIN-1/2, in the multistep carcinogenesis in cholangiocarcinoma associated with hepatolithiasis. Autoph-agy may be involved in the occurrence and development of cholangiocarcinoma","Source":"Google Scholar","category":"HUMAN","training_data":"Autophagy May Be An Early Event In The Stepwise Carcinogenesis Via Biliary Intraepithelial Neoplasia In Cholangiocarcinoma Associated With Hepatolithiasis ackgrounds/Aims. Similar to the pancreatic intraepithelial neoplasia (PanIN)-pancreatic carcinoma sequence model, chol-angiocarcinoma is also reported to follow a stepwise carcino-genesis process and arise from the precursor lesion biliary intraepithelial neoplasia (BilIN). We have previously disclosed that cellular senescence participates in cholangiocarcinogen-esis in the large bile duct via BilIN and the overexpression of EZH2 plays a role in the bypass/escape from senescence followed by the development of overt carcinoma. Accumulating data suggest that autophagy play an important role in occur-rence and development of carcinomas and that autophagy pre-cedes cellular senescence. We examined whether autophagy may be involved in the multistep carcinogenesis in cholangio-carcinoma associated with hepatolithiasis. Methods. Thirty-five cases of hepatolithiasis associated with BilIN and /or chol-angiocarcinoma, 7 of intrahepatic cholangiocarcinoma, 8 of intraductal papillary neoplasm of the bile duct (IPNB) and 6 control livers were surveyed and lesions were categorized into the following: invasive carcinoma (n=16), IPNB (n=8), BIlN-3 (n=16), BilIN-1/2 (n=41), normal large bile duct (LBD, n=56) and peribiliary gland (PBG, n=54). We examined the immu-nohistochemical expressions of autophagy related proteins, microtubule-associated proteins-light chain 3β (LC3), Beclin-1 and p62/sequestosome-1 (p62). The extent of expression was semiquantitatively assessed using scores 0 to 3 (% of posi-tive cells, 0, <5%; 1, 5-30%; 2, 30-70%; 3, >70%). Results. The expression of LC3 (cytoplasmic, vesicular), Beclin-1 (cyto-plasmic) and p62 (cytoplasmic and nuclear) was significantly high in BilIN-1/2, compared to LBD and PBG (p<0.01). The expression of LC3, Beclin-1 and p62 was also significantly high in BilIN-3, IPNB and invasive carcinoma (p<0.05), com-pared to LBD and PBG. There was no significant difference in the expression of autophagy-related proteins in LBD and PBG between cases with and without hepatolithiasis. In conclusion, this study firstly disclosed that the expression of autophagy-re-lated proteins, LC3, Beclin-1 and p62, was upregulated at the early stage, BilIN-1/2, in the multistep carcinogenesis in cholangiocarcinoma associated with hepatolithiasis. Autoph-agy may be involved in the occurrence and development of cholangiocarcinoma Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"characterization gut microbiota bile acid metabolism cytokines intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc type bile duct cancer high mortality rate gut microbiota bile acid ba metabolism cytokines characterized patients icc better noninvasive diagnostic approaches icc essential established therefore study aimed improve understanding changes gut microbiota ba metabolism cytokines patients icc found diversities diversities icc highest abundances four genera lactobacillus actinomyces peptostreptococcaceae alloscardovia increased patients icc compared patients hepatocellular carcinoma liver cirrhosis healthy individuals glycoursodeoxycholic acid tauroursodeoxycholic acid tudca plasma stool ratios obviously increased patients icc furthermore genera lactobacillus alloscardovia positively correlated tudca plasma stool ratios combined discriminate icc three diseases vascular invasion vi frequently led poor prognosis patients icc compared patients icc without vi patients vi greater abundance family ruminococcaceae increased levels plasma interleukin il 4 six conjugated bas decreased levels plasma il 6 chenodeoxycholic acid positive correlation plasma taurocholic acid il 4 observed patients icc plasma tudca negatively correlated abundance genus pseudoramibacter survival time patients icc effect tumor size determined two murine tumor models conclusion study identified biomarkers including gut microbiota bas inflammatory cytokines diagnosis icc prediction vi patients icc stn","probabilities":0.9799733,"Title":"Characterization Of Gut Microbiota Bile Acid Metabolism And Cytokines In Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC), a type of bile duct cancer, has a high mortality rate. Gut microbiota, bile acid (BA) metabolism, and cytokines have not been characterized in patients with ICC, and better noninvasive diagnostic approaches for ICC are essential to be established. Therefore, in this study we aimed to improve our understanding of changes in gut microbiota, BA metabolism, and cytokines in patients with ICC. We found that the α-diversities and β-diversities of ICC were highest and that the abundances of four genera (Lactobacillus, Actinomyces, Peptostreptococcaceae, and Alloscardovia) were increased in patients with ICC compared with those in patients with hepatocellular carcinoma or liver cirrhosis and in healthy individuals. The glycoursodeoxycholic acid and tauroursodeoxycholic acid (TUDCA) plasma-stool ratios were obviously increased in patients with ICC. Furthermore, the genera Lactobacillus and Alloscardovia that were positively correlated with TUDCA plasma-stool ratios were combined to discriminate ICC from the other three diseases. Vascular invasion (VI) frequently led to a poor prognosis in patients with ICC. Compared with patients with ICC without VI, patients with VI had a greater abundance of the family Ruminococcaceae, increased levels of plasma interleukin (IL)-4 and six conjugated BAs, and decreased levels of plasma IL-6 and chenodeoxycholic acid. A positive correlation between plasma taurocholic acid and IL-4 was observed in patients with ICC. Plasma TUDCA was negatively correlated with the abundance of the genus Pseudoramibacter and the survival time of patients with ICC, but had no effect on tumor size, as determined in two murine tumor models. Conclusion: In this study, we identified some biomarkers, including gut microbiota, BAs and inflammatory cytokines, for the diagnosis of ICC and prediction of VI in patients with ICC.","Source":"STN","category":"ANIMAL","training_data":"Characterization Of Gut Microbiota Bile Acid Metabolism And Cytokines In Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC), a type of bile duct cancer, has a high mortality rate. Gut microbiota, bile acid (BA) metabolism, and cytokines have not been characterized in patients with ICC, and better noninvasive diagnostic approaches for ICC are essential to be established. Therefore, in this study we aimed to improve our understanding of changes in gut microbiota, BA metabolism, and cytokines in patients with ICC. We found that the α-diversities and β-diversities of ICC were highest and that the abundances of four genera (Lactobacillus, Actinomyces, Peptostreptococcaceae, and Alloscardovia) were increased in patients with ICC compared with those in patients with hepatocellular carcinoma or liver cirrhosis and in healthy individuals. The glycoursodeoxycholic acid and tauroursodeoxycholic acid (TUDCA) plasma-stool ratios were obviously increased in patients with ICC. Furthermore, the genera Lactobacillus and Alloscardovia that were positively correlated with TUDCA plasma-stool ratios were combined to discriminate ICC from the other three diseases. Vascular invasion (VI) frequently led to a poor prognosis in patients with ICC. Compared with patients with ICC without VI, patients with VI had a greater abundance of the family Ruminococcaceae, increased levels of plasma interleukin (IL)-4 and six conjugated BAs, and decreased levels of plasma IL-6 and chenodeoxycholic acid. A positive correlation between plasma taurocholic acid and IL-4 was observed in patients with ICC. Plasma TUDCA was negatively correlated with the abundance of the genus Pseudoramibacter and the survival time of patients with ICC, but had no effect on tumor size, as determined in two murine tumor models. Conclusion: In this study, we identified some biomarkers, including gut microbiota, BAs and inflammatory cytokines, for the diagnosis of ICC and prediction of VI in patients with ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"differences phosphatidylcholine bile acids bile egyptian uk patients without cholangiocarcinoma background cholangiocarcinoma cc fatal malignancy incidence increasing worldwide substantial regional variation current diagnostic techniques distinguish benign malignant biliary disease unsatisfactory metabolic profiling bile may help differentiate benign malignant disease previous studies compared metabolic profiles bile two geographically racially distinct groups cc patients objectives study aimed compare metabolic profiles bile using vitro proton magnetic resonance spectroscopy cc patients egypt uk patients cc patients non malignant biliary disease methods total 29 bile samples collected cholangiography analysed using 11 7 system samples eight cc patients either egypt n 4 uk n 4 21 patients benign biliary disease choledocholithiasis n 8 sphincter oddi dysfunction n 8 primary sclerosing cholangitis n 5 results bile phosphatidylcholine ptc significantly reduced cc patients egyptian cc patients significantly lower biliary ptc levels compared uk patients taurine glycine conjugated bile acids h 26 h 25 protons respectively significantly elevated bile patients cc compared bile patients benign diseases p 0 013 p 0 01 respectively conclusions biliary ptc levels potentially differentiate cc benign biliary disease reduced biliary ptc egyptian compared uk patients may reflect underlying carcinogenic mechanisms stn","probabilities":0.9799733,"Title":"Differences In Phosphatidylcholine And Bile Acids In Bile From Egyptian And Uk Patients With And Without Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinoma (CC) is a fatal malignancy, the incidence of which is increasing worldwide, with substantial regional variation. Current diagnostic techniques to distinguish benign from malignant biliary disease are unsatisfactory. Metabolic profiling of bile may help to differentiate benign from malignant disease. No previous studies have compared the metabolic profiles of bile from two geographically and racially distinct groups of CC patients. \r\n\r\n Objectives: This study aimed to compare metabolic profiles of bile, using in vitro proton magnetic resonance spectroscopy, from CC patients from Egypt and the UK, and from patients with CC and patients with non-malignant biliary disease. \r\n\r\n Methods: A total of 29 bile samples, collected at cholangiography, were analysed using an 11.7-T system. Samples were from eight CC patients in either Egypt (n = 4) or the UK (n = 4) and 21 patients with benign biliary disease (choledocholithiasis [n = 8], sphincter of Oddi dysfunction [n = 8], primary sclerosing cholangitis [n = 5]). \r\n\r\n Results: Bile phosphatidylcholine (PtC) was significantly reduced in CC patients. Egyptian CC patients had significantly lower biliary PtC levels compared with UK patients. Taurine- and glycine-conjugated bile acids (H-26 and H-25 protons, respectively) were significantly elevated in bile from patients with CC compared with bile from patients with benign diseases (P = 0.013 and P < 0.01, respectively). \r\n\r\n Conclusions: Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms.","Source":"STN","category":"ANIMAL","training_data":"Differences In Phosphatidylcholine And Bile Acids In Bile From Egyptian And Uk Patients With And Without Cholangiocarcinoma Background: Cholangiocarcinoma (CC) is a fatal malignancy, the incidence of which is increasing worldwide, with substantial regional variation. Current diagnostic techniques to distinguish benign from malignant biliary disease are unsatisfactory. Metabolic profiling of bile may help to differentiate benign from malignant disease. No previous studies have compared the metabolic profiles of bile from two geographically and racially distinct groups of CC patients. \r\n\r\n Objectives: This study aimed to compare metabolic profiles of bile, using in vitro proton magnetic resonance spectroscopy, from CC patients from Egypt and the UK, and from patients with CC and patients with non-malignant biliary disease. \r\n\r\n Methods: A total of 29 bile samples, collected at cholangiography, were analysed using an 11.7-T system. Samples were from eight CC patients in either Egypt (n = 4) or the UK (n = 4) and 21 patients with benign biliary disease (choledocholithiasis [n = 8], sphincter of Oddi dysfunction [n = 8], primary sclerosing cholangitis [n = 5]). \r\n\r\n Results: Bile phosphatidylcholine (PtC) was significantly reduced in CC patients. Egyptian CC patients had significantly lower biliary PtC levels compared with UK patients. Taurine- and glycine-conjugated bile acids (H-26 and H-25 protons, respectively) were significantly elevated in bile from patients with CC compared with bile from patients with benign diseases (P = 0.013 and P < 0.01, respectively). \r\n\r\n Conclusions: Biliary PtC levels potentially differentiate CC from benign biliary disease. Reduced biliary PtC in Egyptian compared with UK patients may reflect underlying carcinogenic mechanisms. STN","prediction_labels":"HUMAN"},{"cleaned":"inhibitory effect survivin promoter regulated oncolytic adenovirus carrying p53 gene gallbladder cancer gene therapy become important strategy treatment malignancies problems remains concerning low gene transferring efficiency poor transgene expression limited targeting specific tumors greatly hampered clinical application tumor gene therapy gallbladder cancer characterized rapid progress poor prognosis aberrantly high expression survivin present study used human tumor specific survivin promoter regulated oncolytic adenovirus vector carrying p53 gene whose anti cancer effect widely confirmed construct wide spectrum specific safe effective gene viral therapy system adsurp p53 examining expression enhanced green fluorecent protein egfp e1a target gene p53 oncolytic adenovirus system validated survivin promoter regulated oncolytic adenovirus high proliferation activity high p53 expression survivin positive gallbladder cancer cells vitro cytotoxicity experiment demonstrated adsurp p53 possessed stronger cytotoxic effect gallbladder cancer cells hepatic cancer cells survival rate eh gb1 cells lower 40 infection adsurp p53 multiplicity infection moi 1 pfu cell rate higher 90 infection ad p53 moi demonstrating adsurp p53 potent cytotoxicity eh gb1 cells tumor growth greatly inhibited nude mice bearing eh gb1 xenografts total dose adsurp p53 1 10 9 pfu terminal dutp nick end labeling tunel revealed apoptotic rate cancer cells 33 4 8 4 oncolytic adenovirus system overcomes long standing shortcomings gene therapy poor transgene expression targeting specific tumors therapeutic effect better traditional ad p53 therapy regimen already market system might used patients advanced gallbladder cancer cancers sensitive chemotherapy radiotherapy lost chance surgical treatment stn","probabilities":0.9467213,"Title":"Inhibitory Effect Of Survivin Promoter-Regulated Oncolytic Adenovirus Carrying P53 Gene Against Gallbladder Cancer","Abstract":"Gene therapy has become an important strategy for treatment of malignancies, but problems remains concerning the low gene transferring efficiency, poor transgene expression and limited targeting specific tumors, which have greatly hampered the clinical application of tumor gene therapy. Gallbladder cancer is characterized by rapid progress, poor prognosis, and aberrantly high expression of Survivin. In the present study, we used a human tumor-specific Survivin promoter-regulated oncolytic adenovirus vector carrying P53 gene, whose anti-cancer effect has been widely confirmed, to construct a wide spectrum, specific, safe, effective gene-viral therapy system, AdSurp-P53. Examining expression of enhanced green fluorecent protein (EGFP), E1A and the target gene P53 in the oncolytic adenovirus system validated that Survivin promoter-regulated oncolytic adenovirus had high proliferation activity and high P53 expression in Survivin-positive gallbladder cancer cells. Our in vitro cytotoxicity experiment demonstrated that AdSurp-P53 possessed a stronger cytotoxic effect against gallbladder cancer cells and hepatic cancer cells. The survival rate of EH-GB1 cells was lower than 40% after infection of AdSurp-P53 at multiplicity of infection (MOI) = 1 pfu/cell, while the rate was higher than 90% after infection of Ad-P53 at the same MOI, demonstrating that AdSurp-P53 has a potent cytotoxicity against EH-GB1 cells. The tumor growth was greatly inhibited in nude mice bearing EH-GB1 xenografts when the total dose of AdSurp-P53 was 1 × 10(9) pfu, and terminal dUTP nick end-labeling (TUNEL) revealed that the apoptotic rate of cancer cells was (33.4 ± 8.4)%. This oncolytic adenovirus system overcomes the long-standing shortcomings of gene therapy: poor transgene expression and targeting of only specific tumors, with its therapeutic effect better than the traditional Ad-P53 therapy regimen already on market; our system might be used for patients with advanced gallbladder cancer and other cancers, who are not sensitive to chemotherapy, radiotherapy, or who lost their chance for surgical treatment.","Source":"STN","category":"ANIMAL","training_data":"Inhibitory Effect Of Survivin Promoter-Regulated Oncolytic Adenovirus Carrying P53 Gene Against Gallbladder Cancer Gene therapy has become an important strategy for treatment of malignancies, but problems remains concerning the low gene transferring efficiency, poor transgene expression and limited targeting specific tumors, which have greatly hampered the clinical application of tumor gene therapy. Gallbladder cancer is characterized by rapid progress, poor prognosis, and aberrantly high expression of Survivin. In the present study, we used a human tumor-specific Survivin promoter-regulated oncolytic adenovirus vector carrying P53 gene, whose anti-cancer effect has been widely confirmed, to construct a wide spectrum, specific, safe, effective gene-viral therapy system, AdSurp-P53. Examining expression of enhanced green fluorecent protein (EGFP), E1A and the target gene P53 in the oncolytic adenovirus system validated that Survivin promoter-regulated oncolytic adenovirus had high proliferation activity and high P53 expression in Survivin-positive gallbladder cancer cells. Our in vitro cytotoxicity experiment demonstrated that AdSurp-P53 possessed a stronger cytotoxic effect against gallbladder cancer cells and hepatic cancer cells. The survival rate of EH-GB1 cells was lower than 40% after infection of AdSurp-P53 at multiplicity of infection (MOI) = 1 pfu/cell, while the rate was higher than 90% after infection of Ad-P53 at the same MOI, demonstrating that AdSurp-P53 has a potent cytotoxicity against EH-GB1 cells. The tumor growth was greatly inhibited in nude mice bearing EH-GB1 xenografts when the total dose of AdSurp-P53 was 1 × 10(9) pfu, and terminal dUTP nick end-labeling (TUNEL) revealed that the apoptotic rate of cancer cells was (33.4 ± 8.4)%. This oncolytic adenovirus system overcomes the long-standing shortcomings of gene therapy: poor transgene expression and targeting of only specific tumors, with its therapeutic effect better than the traditional Ad-P53 therapy regimen already on market; our system might be used for patients with advanced gallbladder cancer and other cancers, who are not sensitive to chemotherapy, radiotherapy, or who lost their chance for surgical treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"photodynamic therapy prolongs metal stent patency patients unresectable hilar cholangiocarcinoma aim evaluate effect photodynamic therapy pdt metal stent patency patients unresectable hilar cholangiocarcinoma cc methods retrospective analysis patients hilar cc referred institution december 1999 january 2011 232 patients thirty three patients unresectable hilar cc treated eighteen patients pdt group treated uncovered metal stents one session pdt fifteen patients control group treated metal stents alone porfimer sodium 2 mg kg administered intravenously pdt patients forty eight hours later pdt administered using diffusing fiber advanced across tumor either endoscopic retrograde cholangiopancreatography percutaneous cholangiography performance pdt uncovered metal stents inserted ensure adequate decompression bile drainage patient survival rates cumulative stent patency calculated using kaplan meier analysis log rank test results pdt control patients comparable respect age gender health status pre treatment bilirubin hilar cc stage compared control pdt group associated significantly prolonged stent patency median 244 66 177 45 d respectively p 0 002 longer patient survival median 356 213 230 73 d respectively p 0 006 early complication rates similar groups pdt group 17 control group 13 patients treated conservatively stent malfunctions occurred 14 pdt patients 78 12 control patients 80 26 patients twenty two treated endoscopically four treated external drainage conclusion metal stenting one session pdt may safe acceptable complication rates pdt group associated significantly longer stent patency control group patients unresectable hilar cc pubmed","probabilities":0.9799733,"Title":"Photodynamic therapy prolongs metal stent patency in patients with unresectable hilar cholangiocarcinoma","Abstract":"AIM: To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS: This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Forty-eight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS: The PDT and control patients were comparable with respect to age, gender, health status, pre-treatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION: Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC.","Source":"PubMed","category":"HUMAN","training_data":"Photodynamic therapy prolongs metal stent patency in patients with unresectable hilar cholangiocarcinoma AIM: To evaluate the effect of photodynamic therapy (PDT) on metal stent patency in patients with unresectable hilar cholangiocarcinoma (CC). METHODS: This was a retrospective analysis of patients with hilar CC referred to our institution from December, 1999 to January, 2011. Out of 232 patients, thirty-three patients with unresectable hilar CC were treated. Eighteen patients in the PDT group were treated with uncovered metal stents after one session of PDT. Fifteen patients in the control group were treated with metal stents alone. Porfimer sodium (2 mg/kg) was administered intravenously to PDT patients. Forty-eight hours later, PDT was administered using a diffusing fiber that was advanced across the tumor by either endoscopic retrograde cholangiopancreatography or percutaneous cholangiography. After performance of PDT, uncovered metal stents were inserted to ensure adequate decompression and bile drainage. Patient survival rates and cumulative stent patency were calculated using Kaplan-Meier analysis with the log-rank test. RESULTS: The PDT and control patients were comparable with respect to age, gender, health status, pre-treatment bilirubin, and hilar CC stage. When compared to control, the PDT group was associated with significantly prolonged stent patency (median 244 ± 66 and 177 ± 45 d, respectively, P = 0.002) and longer patient survival (median 356 ± 213 and 230 ± 73 d, respectively, P = 0.006). Early complication rates were similar between the groups (PDT group 17%, control group 13%) and all patients were treated conservatively. Stent malfunctions occurred in 14 PDT patients (78%) and 12 control patients (80%). Of these 26 patients, twenty-two were treated endoscopically and four were treated with external drainage. CONCLUSION: Metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency than the control group in patients with unresectable hilar CC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"staging prognostic models hepatocellular carcinoma intrahepatic cholangiocarcinoma several important roles staging systems prognostic models play modern medical care patients cancer first accurate staging systems assist clinicians identifying optimal treatment selection based scope disease time diagnosis second physicians patients may infer prognostic information staging models may help decision makers identify appropriate therapies individual patients third research benefit classifying patients disease subgroups ensuring greater parity experimental control arms staging systems solid organ malignancies rely heavily accurate pathologic assessment tumor size site number tumors locoregional spread distant spread another consideration primary liver cancer hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc fact underlying liver function significantly impact patient survival hcc least dozen options proposed staging disease herein review widely used systems discuss strengths weaknesses prognostic models nomograms also discussed variety subpopulations hcc interestingly 2010 staging system proposed american joint committee cancer icc identical hcc modern staging system unique icc reviewed future modifications identified primary supporting literature discussed pubmed","probabilities":0.9799733,"Title":"Staging and Prognostic Models for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma","Abstract":"There are several important roles that staging systems and prognostic models play in the modern medical care of patients with cancer. First, accurate staging systems can assist clinicians by identifying optimal treatment selection based on the scope of disease at the time of diagnosis. Second, both physicians and patients may infer prognostic information from staging and models that may help decision makers identify appropriate therapies for individual patients. Third, in research, there is benefit to classifying patients with disease into subgroups ensuring greater parity between experimental and control arms. Staging systems in most solid organ malignancies rely heavily on an accurate pathologic assessment of the tumor (size, site, number of tumors, locoregional spread, and distant spread). Another consideration in primary liver cancer, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the fact that the underlying liver function can significantly impact patient survival. In HCC, there are at least a dozen options that have been proposed for staging the disease. Herein, we review the most widely used systems and discuss their strengths and weaknesses. Prognostic models and nomograms are also discussed for a variety of subpopulations with HCC. Interestingly, until 2010, the staging system proposed by the American Joint Committee on Cancer for ICC was identical to HCC. The modern staging system, unique to ICC, is reviewed, and future modifications are identified with the primary supporting literature discussed.","Source":"PubMed","category":"HUMAN","training_data":"Staging and Prognostic Models for Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma There are several important roles that staging systems and prognostic models play in the modern medical care of patients with cancer. First, accurate staging systems can assist clinicians by identifying optimal treatment selection based on the scope of disease at the time of diagnosis. Second, both physicians and patients may infer prognostic information from staging and models that may help decision makers identify appropriate therapies for individual patients. Third, in research, there is benefit to classifying patients with disease into subgroups ensuring greater parity between experimental and control arms. Staging systems in most solid organ malignancies rely heavily on an accurate pathologic assessment of the tumor (size, site, number of tumors, locoregional spread, and distant spread). Another consideration in primary liver cancer, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the fact that the underlying liver function can significantly impact patient survival. In HCC, there are at least a dozen options that have been proposed for staging the disease. Herein, we review the most widely used systems and discuss their strengths and weaknesses. Prognostic models and nomograms are also discussed for a variety of subpopulations with HCC. Interestingly, until 2010, the staging system proposed by the American Joint Committee on Cancer for ICC was identical to HCC. The modern staging system, unique to ICC, is reviewed, and future modifications are identified with the primary supporting literature discussed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"defining chance statistical cure among patients extrahepatic biliary tract cancer background surgery offers best curative intent treatment many patients biliary tract malignancies poor long term outcomes sought apply non mixture cure model calculate cure fraction time cure surgery patients peri hilar cholangiocarcinoma phcc gallbladder cancer gbc methods using extrahepatic biliary malignancy consortium 576 patients underwent curative intent surgery gallbladder carcinoma peri hilar cholangiocarcinoma 1998 2014 10 major hepatobiliary institutions identified included analysis non mixture cure model adopted compare mortality surgery mortality expected general population matched sex age results median 5 year overall survival os 1 9 years iqr 0 9 4 9 23 9 95 ci 19 6 28 6 among patients phcc gbc probability cured surgery 14 5 95 ci 8 7 23 2 time cure 9 7 years median survival uncured patients 1 8 years determinants cure probabilities included lymph node metastasis ca 19 9 level p 0 05 cure fraction patients ca 19 9 50 u ml lymph nodes metastases 39 0 versus 5 1 among patients ca 19 9 50 also lymph node metastasis conclusions examining comer cohort 15 patients phcc gbc considered cured surgery factors ca 19 9 level lymph node metastasis independently predicted long term outcome estimating odds statistical cure following surgery biliary tract cancer assist decision making well inform discussions around survivorship pubmed","probabilities":0.9799733,"Title":"Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer","Abstract":"BACKGROUND: While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC). METHODS: Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non-mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age. RESULTS: The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9-4.9) and 23.9 % (95 % CI, 19.6-28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7-23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p ≤ 0.05). The cure fraction for patients with a CA 19.9 < 50 U/ml and no lymph nodes metastases were 39.0 % versus only 5.1 % among patients with a CA 19.9 ≥ 50 who also had lymph node metastasis. CONCLUSIONS: Examining an \"all comer\" cohort, <15 % of patients with PHCC or GBC could be considered cured after surgery. Factors such CA 19.9 level and lymph node metastasis independently predicted long-term outcome. Estimating the odds of statistical cure following surgery for biliary tract cancer can assist in decision-making as well as inform discussions around survivorship.","Source":"PubMed","category":"HUMAN","training_data":"Defining the Chance of Statistical Cure Among Patients with Extrahepatic Biliary Tract Cancer BACKGROUND: While surgery offers the best curative-intent treatment, many patients with biliary tract malignancies have poor long-term outcomes. We sought to apply a non-mixture cure model to calculate the cure fraction and the time to cure after surgery of patients with peri-hilar cholangiocarcinoma (PHCC) or gallbladder cancer (GBC). METHODS: Using the Extrahepatic Biliary Malignancy Consortium, 576 patients who underwent curative-intent surgery for gallbladder carcinoma or peri-hilar cholangiocarcinoma between 1998 and 2014 at 10 major hepatobiliary institutions were identified and included in the analysis. A non-mixture cure model was adopted to compare mortality after surgery to the mortality expected for the general population matched by sex and age. RESULTS: The median and 5-year overall survival (OS) were 1.9 years (IQR, 0.9-4.9) and 23.9 % (95 % CI, 19.6-28.6). Among all patients with PHCC or GBC, the probability of being cured after surgery was 14.5 % (95 % CI, 8.7-23.2); the time to cure was 9.7 years and the median survival of uncured patients was 1.8 years. Determinants of cure probabilities included lymph node metastasis and CA 19.9 level (p ≤ 0.05). The cure fraction for patients with a CA 19.9 < 50 U/ml and no lymph nodes metastases were 39.0 % versus only 5.1 % among patients with a CA 19.9 ≥ 50 who also had lymph node metastasis. CONCLUSIONS: Examining an \"all comer\" cohort, <15 % of patients with PHCC or GBC could be considered cured after surgery. Factors such CA 19.9 level and lymph node metastasis independently predicted long-term outcome. Estimating the odds of statistical cure following surgery for biliary tract cancer can assist in decision-making as well as inform discussions around survivorship. PubMed","prediction_labels":"HUMAN"},{"cleaned":"risk cholangiocarcinoma patients primary sclerosing cholangitis diagnosis surveillance purpose review primary sclerosing cholangitis psc associated increased risk hepatobiliary extrahepatic malignancy particularly risk cholangiocarcinoma cca greatly increased provide potentially curative treatments affected patients early diagnosis cca crucial review current advances respect cca diagnosis surveillance discuss rational approach perform surveillance cca psc patients recent findings given shortcomings current modalities surveillance diagnosis cca psc recent studies focused novel biomarkers cca include serum biomarkers e g circulating angiopoeitin 2 cytokeratin 19 fragments antiglycoprotein 2 iga autoantibodies microrna well proteomics obtained urine bile novel approaches may enhance diagnostic value brush cytology future include optimization fluorescence situ hybridization probes assessment genetic aberrations addition studies advanced techniques e g single operator cholangioscopy probe based confocal laser endomicroscopy shown promising results respect cca detection summary despite recent advances diagnosis cca psc detection early stage cca remains difficult better understanding cca pathogenesis large prospective studies novel biomarkers techniques required timely diagnose cca future pubmed","probabilities":0.9799733,"Title":"Risk of cholangiocarcinoma in patients with primary sclerosing cholangitis: diagnosis and surveillance","Abstract":"PURPOSE OF REVIEW: Primary sclerosing cholangitis (PSC) is associated with an increased risk of hepatobiliary and extrahepatic malignancy. Particularly the risk of cholangiocarcinoma (CCA) is greatly increased. To provide potentially curative treatments for affected patients an early diagnosis of CCA is crucial. We here review the current advances with respect to CCA diagnosis and surveillance and discuss a rational approach on how to perform surveillance of CCA in PSC patients. RECENT FINDINGS: Given the shortcomings of the current modalities for the surveillance and diagnosis of CCA in PSC, recent studies have focused on novel biomarkers for CCA. These include serum biomarkers (e.g., circulating angiopoeitin-2, cytokeratin-19 fragments, and antiglycoprotein 2 IgA autoantibodies, microRNA) as well as proteomics obtained from urine and/or bile. Novel approaches that may enhance the diagnostic value of brush cytology in future include the optimization of fluorescence in situ hybridization probes and the assessment of genetic aberrations. In addition, studies on advanced techniques (e.g., single-operator cholangioscopy and probe-based confocal laser endomicroscopy) have shown promising results with respect to CCA detection. SUMMARY: Despite recent advances in the diagnosis of CCA in PSC, the detection of early-stage CCA remains difficult. A better understanding of CCA pathogenesis and large prospective studies on novel biomarkers and techniques are required to timely diagnose CCA in the future.","Source":"PubMed","category":"HUMAN","training_data":"Risk of cholangiocarcinoma in patients with primary sclerosing cholangitis: diagnosis and surveillance PURPOSE OF REVIEW: Primary sclerosing cholangitis (PSC) is associated with an increased risk of hepatobiliary and extrahepatic malignancy. Particularly the risk of cholangiocarcinoma (CCA) is greatly increased. To provide potentially curative treatments for affected patients an early diagnosis of CCA is crucial. We here review the current advances with respect to CCA diagnosis and surveillance and discuss a rational approach on how to perform surveillance of CCA in PSC patients. RECENT FINDINGS: Given the shortcomings of the current modalities for the surveillance and diagnosis of CCA in PSC, recent studies have focused on novel biomarkers for CCA. These include serum biomarkers (e.g., circulating angiopoeitin-2, cytokeratin-19 fragments, and antiglycoprotein 2 IgA autoantibodies, microRNA) as well as proteomics obtained from urine and/or bile. Novel approaches that may enhance the diagnostic value of brush cytology in future include the optimization of fluorescence in situ hybridization probes and the assessment of genetic aberrations. In addition, studies on advanced techniques (e.g., single-operator cholangioscopy and probe-based confocal laser endomicroscopy) have shown promising results with respect to CCA detection. SUMMARY: Despite recent advances in the diagnosis of CCA in PSC, the detection of early-stage CCA remains difficult. A better understanding of CCA pathogenesis and large prospective studies on novel biomarkers and techniques are required to timely diagnose CCA in the future. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ca 19 9 prognostic relevance gallbladder carcinoma gbc background scarce data prognostic relevance carbohydrate antigen ca 19 9 retrospective study undertaken evaluate prognostic relevance different prognostic subsets gallbladder carcinoma gbc materials methods one hundred forty one patients gbc treated january 2012 december 2014 subjects retrospective analysis baseline ca 19 9 levels four cohorts patients extended cholecystectomy ec simple cholecystectomy sc residual recurrent disease locally advanced disease lagbc metastatic disease ascertained difference median baseline values among groups ascertained effect clinicopathological variables treatment related variables ca 19 9 overall survival os also evaluated auc curve computed evaluate performance results median baseline levels ca 19 9 significantly different 10 units ml 24 units ml 48 units ml 75 units ml ec n 33 sc n 21 lagbc n 38 metastatic disease n 49 respectively p value 0 001 median os also significantly different 24 15 7 6 months ec sc lagbc metastatic disease respectively p value 0 001 univariate analysis revealed significant influence log transformed value ca 19 9 ca 19 9 levels 20 units 35 units surgery vs none chemoradiation vs chemotherapy os multivariate analysis treatment related variables significant hr 1 1 95 ci 1 026 1 19 p 0 009 auc curve 0 63 patients 0 72 ec group conclusions median values baseline ca 19 9 predict burden disease raised levels serum ca 19 9 beyond 20 units ml used prognostication purposes ec level beyond 35 units trend towards prognostication prognostic groups needs evaluated large subset patients pubmed","probabilities":0.9799733,"Title":"Does CA 19-9 Have Prognostic Relevance in Gallbladder Carcinoma (GBC)?","Abstract":"BACKGROUND: There is a scarce data on prognostic relevance of carbohydrate antigen (CA 19-9). This retrospective study was undertaken to evaluate its prognostic relevance in different prognostic subsets of gallbladder carcinoma (GBC). MATERIALS AND METHODS: One hundred forty-one patients of GBC treated between January 2012 and December 2014 were the subjects of this retrospective analysis. Baseline CA 19-9 levels of four cohorts of patients: extended cholecystectomy (EC), simple cholecystectomy (SC) with residual or recurrent disease, locally advanced disease (LAGBC) and metastatic disease were ascertained. The difference in its median baseline values among above groups was ascertained. The effect of clinicopathological variables, treatment-related variables and CA 19-9 on overall survival (OS) was also evaluated. AUC curve was computed to evaluate its performance. RESULTS: The median baseline levels of CA 19-9 were significantly different [10 units/ml, 24 units/ml, 48 units/ml and 75 units/ml in EC (n = 33), SC (n = 21), LAGBC (n = 38) and metastatic disease (n = 49), respectively, (p value 0.001)]. The median OS was also significantly different [24, 15, 7 and 6 months in EC, SC, LAGBC and metastatic disease, respectively, (p value 0.001)]. Univariate analysis revealed a significant influence of log transformed value of CA 19-9, CA 19-9 levels < or >20 units or 35 units, surgery vs. none and chemoradiation vs. chemotherapy on OS. On multivariate analysis, only treatment-related variables were significant (HR 1.1, 95% CI 1.026-1.19, p = 0.009). AUC curve was 0.63 for all patients and 0.72 for EC group. CONCLUSIONS: The median values of baseline CA 19-9 predict the burden of disease. Raised levels of serum CA 19-9 beyond 20 units/ml should be used for prognostication purposes after EC. A level beyond 35 units has a trend towards prognostication in other prognostic groups and needs to be evaluated in large subset of patients.","Source":"PubMed","category":"HUMAN","training_data":"Does CA 19-9 Have Prognostic Relevance in Gallbladder Carcinoma (GBC)? BACKGROUND: There is a scarce data on prognostic relevance of carbohydrate antigen (CA 19-9). This retrospective study was undertaken to evaluate its prognostic relevance in different prognostic subsets of gallbladder carcinoma (GBC). MATERIALS AND METHODS: One hundred forty-one patients of GBC treated between January 2012 and December 2014 were the subjects of this retrospective analysis. Baseline CA 19-9 levels of four cohorts of patients: extended cholecystectomy (EC), simple cholecystectomy (SC) with residual or recurrent disease, locally advanced disease (LAGBC) and metastatic disease were ascertained. The difference in its median baseline values among above groups was ascertained. The effect of clinicopathological variables, treatment-related variables and CA 19-9 on overall survival (OS) was also evaluated. AUC curve was computed to evaluate its performance. RESULTS: The median baseline levels of CA 19-9 were significantly different [10 units/ml, 24 units/ml, 48 units/ml and 75 units/ml in EC (n = 33), SC (n = 21), LAGBC (n = 38) and metastatic disease (n = 49), respectively, (p value 0.001)]. The median OS was also significantly different [24, 15, 7 and 6 months in EC, SC, LAGBC and metastatic disease, respectively, (p value 0.001)]. Univariate analysis revealed a significant influence of log transformed value of CA 19-9, CA 19-9 levels < or >20 units or 35 units, surgery vs. none and chemoradiation vs. chemotherapy on OS. On multivariate analysis, only treatment-related variables were significant (HR 1.1, 95% CI 1.026-1.19, p = 0.009). AUC curve was 0.63 for all patients and 0.72 for EC group. CONCLUSIONS: The median values of baseline CA 19-9 predict the burden of disease. Raised levels of serum CA 19-9 beyond 20 units/ml should be used for prognostication purposes after EC. A level beyond 35 units has a trend towards prognostication in other prognostic groups and needs to be evaluated in large subset of patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term survival patients cholangiolocellular carcinoma curative hepatectomy background cholangiolocellular carcinoma cocc distinct pathological characteristics cocc considered originate hepatic progenitor stem cells however surgical outcome cocc clarified detail methods retrospectively studied 275 patients intrahepatic cholangiocarcinoma icc underwent hepatectomy 1990 2011 surgical outcomes compared 29 patients cocc 130 patients mass forming mf type icc since patients cocc showed mf type macroscopic findings results number patients chronic liver disease significantly higher cocc group icc group number patients abnormal levels ca19 9 significantly lower cocc group icc group portal vein invasion intrahepatic metastasis significantly lower patients cocc group icc group cocc group 15 28 patients survived 5 years curative surgery whereas 15 102 patients icc survived 5 years curative surgery 5 year survival rate significantly higher patients cocc 75 patients icc 33 p 0 0005 multivariate analysis showed cocc absence portal vein invasion hepatic vein invasion absence intrahepatic metastasis significant independent prognostic factors overall survival patients mf type icc cocc conclusions cocc rare patients cocc special characteristics favorable long term survival due less invasive histopathologic characteristics pubmed","probabilities":0.9799733,"Title":"Long-term survival of patients with cholangiolocellular carcinoma after curative hepatectomy","Abstract":"BACKGROUND: Cholangiolocellular carcinoma (CoCC) has distinct pathological characteristics, and CoCC is considered to originate from hepatic progenitor or stem cells. However, the surgical outcome of CoCC has not been clarified in detail. METHODS: We retrospectively studied 275 patients with intrahepatic cholangiocarcinoma (ICC) who underwent hepatectomy between 1990 and 2011. Surgical outcomes were compared between 29 patients with CoCC and 130 patients with mass-forming (MF) type ICC since all patients with CoCC showed MF type on macroscopic findings. RESULTS: The number of patients with chronic liver disease was significantly higher in the CoCC group than in the ICC group. The number of patients with abnormal levels of CA19-9 was significantly lower in the CoCC group than in the ICC group. Portal vein invasion and intrahepatic metastasis were significantly lower in patients with CoCC group than in the ICC group. In the CoCC group, 15 of 28 patients survived for more than 5 years after curative surgery whereas 15 of 102 patients with ICC survived for more than 5 years after curative surgery. The 5-year survival rate was significantly higher in patients with CoCC (75 %) than in patients with ICC (33 %, p = 0.0005). Multivariate analysis showed CoCC, absence of portal vein invasion or hepatic vein invasion, and absence of intrahepatic metastasis to be significant independent prognostic factors for overall survival in patients with MF-type ICC and CoCC. CONCLUSIONS: CoCC is rare, but patients with CoCC had special characteristics with favorable long-term survival due to its less invasive histopathologic characteristics.","Source":"PubMed","category":"HUMAN","training_data":"Long-term survival of patients with cholangiolocellular carcinoma after curative hepatectomy BACKGROUND: Cholangiolocellular carcinoma (CoCC) has distinct pathological characteristics, and CoCC is considered to originate from hepatic progenitor or stem cells. However, the surgical outcome of CoCC has not been clarified in detail. METHODS: We retrospectively studied 275 patients with intrahepatic cholangiocarcinoma (ICC) who underwent hepatectomy between 1990 and 2011. Surgical outcomes were compared between 29 patients with CoCC and 130 patients with mass-forming (MF) type ICC since all patients with CoCC showed MF type on macroscopic findings. RESULTS: The number of patients with chronic liver disease was significantly higher in the CoCC group than in the ICC group. The number of patients with abnormal levels of CA19-9 was significantly lower in the CoCC group than in the ICC group. Portal vein invasion and intrahepatic metastasis were significantly lower in patients with CoCC group than in the ICC group. In the CoCC group, 15 of 28 patients survived for more than 5 years after curative surgery whereas 15 of 102 patients with ICC survived for more than 5 years after curative surgery. The 5-year survival rate was significantly higher in patients with CoCC (75 %) than in patients with ICC (33 %, p = 0.0005). Multivariate analysis showed CoCC, absence of portal vein invasion or hepatic vein invasion, and absence of intrahepatic metastasis to be significant independent prognostic factors for overall survival in patients with MF-type ICC and CoCC. CONCLUSIONS: CoCC is rare, but patients with CoCC had special characteristics with favorable long-term survival due to its less invasive histopathologic characteristics. PubMed","prediction_labels":"HUMAN"},{"cleaned":"staging peripheral type intrahepatic cholangiocarcinoma appraisal new tnm classification modifications background seventh edition tnm classification intrahepatic cholangiocarcinoma ihc separated hepatocellular carcinoma first independent classification ihc validity new classification needs evaluated methods medical records 93 patients peripheral type ihc underwent treatment 61 resected 32 unresectable tumors retrospectively reviewed focusing new tnm classification ihc results 5 year survival rate median survival time 61 patients resected tumors 33 9 2 05 years respectively survival patients periductal invasion similar patients without survival patients metastasis gastrohepatic lymph nodes g ln dismal without 2 year survivors similar patients unresectable tumors p 0 247 multivariate analysis histologic differentiation p 0 034 multiple tumors p 0 014 lymph node metastasis p 0 001 distant metastasis lymph node metastasis p 0 007 identified independent prognostic factors according results modified new tnm classification follows ihc multiple tumors classified pt4 disease periductal invasion excluded determinant categories metastasis g ln treated distant metastasis survival curves based modifications better stratified based new tnm classification conclusions tnm classification ihc included clinical inconsistencies therefore proposed modifications new tnm classification ihc demonstrated modifications offer better stratification survival data revisions necessary improvement pubmed","probabilities":0.9799733,"Title":"Staging of peripheral-type intrahepatic cholangiocarcinoma: appraisal of the new TNM classification and its modifications","Abstract":"BACKGROUND: In the seventh edition, the TNM classification for intrahepatic cholangiocarcinoma (IHC) is separated from that for hepatocellular carcinoma. Because it is the first independent classification for IHC, the validity of the new classification needs to be evaluated. METHODS: The medical records of 93 patients with peripheral-type IHC who underwent treatment (61 resected and 32 unresectable tumors) were retrospectively reviewed focusing on the new TNM classification for IHC. RESULTS: The 5-year survival rate and the median survival time for the 61 patients with resected tumors were 33.9% and 2.05 years, respectively. The survival of the patients with periductal invasion was similar to that of the patients without. The survival of the patients with metastasis to the gastrohepatic lymph nodes (G-LN) was dismal without any 2-year survivors and similar to that of the patients with unresectable tumors (P = 0.247). On multivariate analysis, histologic differentiation (P = 0.034), multiple tumors (P = 0.014), lymph node metastasis (P < 0.001), and distant metastasis other than lymph node metastasis (P = 0.007) were identified as independent prognostic factors. According to the above results, we modified the new TNM classification as follows: IHC with multiple tumors was classified as pT4 disease; periductal invasion was excluded from determinant of the T-categories; and metastasis to G-LN was treated as distant metastasis. The survival curves based on our modifications were better stratified than those based on the new TNM classification. CONCLUSIONS: The TNM classification for IHC included some clinical inconsistencies; therefore, we proposed some modifications of the new TNM classification for IHC and demonstrated that these modifications offer better stratification of the survival data. Further revisions are necessary for its improvement.","Source":"PubMed","category":"HUMAN","training_data":"Staging of peripheral-type intrahepatic cholangiocarcinoma: appraisal of the new TNM classification and its modifications BACKGROUND: In the seventh edition, the TNM classification for intrahepatic cholangiocarcinoma (IHC) is separated from that for hepatocellular carcinoma. Because it is the first independent classification for IHC, the validity of the new classification needs to be evaluated. METHODS: The medical records of 93 patients with peripheral-type IHC who underwent treatment (61 resected and 32 unresectable tumors) were retrospectively reviewed focusing on the new TNM classification for IHC. RESULTS: The 5-year survival rate and the median survival time for the 61 patients with resected tumors were 33.9% and 2.05 years, respectively. The survival of the patients with periductal invasion was similar to that of the patients without. The survival of the patients with metastasis to the gastrohepatic lymph nodes (G-LN) was dismal without any 2-year survivors and similar to that of the patients with unresectable tumors (P = 0.247). On multivariate analysis, histologic differentiation (P = 0.034), multiple tumors (P = 0.014), lymph node metastasis (P < 0.001), and distant metastasis other than lymph node metastasis (P = 0.007) were identified as independent prognostic factors. According to the above results, we modified the new TNM classification as follows: IHC with multiple tumors was classified as pT4 disease; periductal invasion was excluded from determinant of the T-categories; and metastasis to G-LN was treated as distant metastasis. The survival curves based on our modifications were better stratified than those based on the new TNM classification. CONCLUSIONS: The TNM classification for IHC included some clinical inconsistencies; therefore, we proposed some modifications of the new TNM classification for IHC and demonstrated that these modifications offer better stratification of the survival data. Further revisions are necessary for its improvement. PubMed","prediction_labels":"HUMAN"},{"cleaned":"anti diabetic drug metformin inhibits cell proliferation tumor growth gallbladder cancer via g0 g1 cell cycle arrest gallbladder cancer common biliary tract cancer poor prognosis wide variation incidence rates worldwide high countries latin america asia treatment type 2 diabetes metformin causes reduction incidence cancer till date reports anti tumor effects metformin gall bladder cancer therefore study evaluated effects metformin proliferation human gallbladder adenocarcinoma cells vitro vivo well explored micrornas associated anti tumor effects metformin metformin inhibited proliferation gallbladder adenocarcinoma cell lines noz tgbc14tkb tgbc24tkb blocked g0 g1 transition cell cycle accompanied strong reduction expression g1 cyclins especially cyclin d1 catalytic subunits including cyclin dependent kinase 4 retinoblastoma protein phosphorylation addition metformin reduced phosphorylation receptor tyrosine kinases especially tie 2 alk pyk epha4 epha10 well angiogenesis related proteins including rantes tgf timp 1 moreover metformin also markedly altered microrna expression profile leading anti tumor effect treatment athymic nude mice bearing xenograft tumors metformin inhibited tumor growth results suggest metformin may used clinically treatment gallbladder adenocarcinoma stn","probabilities":0.9467213,"Title":"Anti-Diabetic Drug Metformin Inhibits Cell Proliferation And Tumor Growth In Gallbladder Cancer Via G0/G1 Cell Cycle Arrest","Abstract":"Gallbladder cancer is the most common biliary tract cancer with poor prognosis and wide variation in incidence rates worldwide, being very high in some countries in Latin America and Asia. Treatment of type 2 diabetes with metformin causes a reduction in the incidence of cancer. Till date, there are no reports on the anti-tumor effects of metformin in gall bladder cancer. Therefore, this study evaluated the effects of metformin on the proliferation of human gallbladder adenocarcinoma cells in vitro and in vivo, as well as explored the microRNAs associated with the anti-tumor effects of metformin. Metformin inhibited the proliferation in gallbladder adenocarcinoma cell lines NOZ, TGBC14TKB, and TGBC24TKB, and blocked the G0 to G1 transition in the cell cycle. This was accompanied by strong reduction in the expression of G1 cyclins, especially cyclin D1 and its catalytic subunits including cyclin-dependent kinase 4, and in retinoblastoma protein phosphorylation. In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-β, and TIMP-1. Moreover, metformin also markedly altered microRNA expression profile leading to an anti-tumor effect. Treatment of athymic nude mice bearing xenograft tumors with metformin inhibited tumor growth. These results suggest that metformin may be used clinically for the treatment of gallbladder adenocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Anti-Diabetic Drug Metformin Inhibits Cell Proliferation And Tumor Growth In Gallbladder Cancer Via G0/G1 Cell Cycle Arrest Gallbladder cancer is the most common biliary tract cancer with poor prognosis and wide variation in incidence rates worldwide, being very high in some countries in Latin America and Asia. Treatment of type 2 diabetes with metformin causes a reduction in the incidence of cancer. Till date, there are no reports on the anti-tumor effects of metformin in gall bladder cancer. Therefore, this study evaluated the effects of metformin on the proliferation of human gallbladder adenocarcinoma cells in vitro and in vivo, as well as explored the microRNAs associated with the anti-tumor effects of metformin. Metformin inhibited the proliferation in gallbladder adenocarcinoma cell lines NOZ, TGBC14TKB, and TGBC24TKB, and blocked the G0 to G1 transition in the cell cycle. This was accompanied by strong reduction in the expression of G1 cyclins, especially cyclin D1 and its catalytic subunits including cyclin-dependent kinase 4, and in retinoblastoma protein phosphorylation. In addition, metformin reduced the phosphorylation of receptor tyrosine kinases, especially Tie-2, ALK, PYK, EphA4, and EphA10, as well as angiogenesis-related proteins, including RANTES, TGF-β, and TIMP-1. Moreover, metformin also markedly altered microRNA expression profile leading to an anti-tumor effect. Treatment of athymic nude mice bearing xenograft tumors with metformin inhibited tumor growth. These results suggest that metformin may be used clinically for the treatment of gallbladder adenocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"multivariate prognostic factors analysis second line chemotherapy advanced biliary tract cancer background role second line chemotherapy ct established advanced biliary tract cancer abtc investigated outcome abtc patients treated second line ct devised prognostic model methods baseline clinical laboratory data 300 consecutive abtc patients collected association overall survival os investigated multivariable cox models results following parameters resulted independently associated longer os eastern cooperative oncology group performance status 0 p 0 001 hazard ratio hr 0 348 95 confidence interval ci 0 215 0 562 ca19 9 lower median p 0 013 hr 0 574 95 ci 0 370 0 891 progression free survival first line ct 6 months p 0 027 hr 0 633 95 ci 0 422 0 949 previous surgery primary tumour p 0 027 hr 0 609 95 ci 0 392 0 945 grouped 249 patients complete data available three categories according number fulfilled risk factors median os times good risk zero one factors intermediate risk two factors poor risk three four factors groups 13 1 6 6 3 7 months respectively p 0 001 conclusions easily available clinical laboratory factors predict prognosis abtc patients undergoing second line ct model allows individual patient risk stratification may help treatment decision trial design pubmed","probabilities":0.9799733,"Title":"Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer","Abstract":"BACKGROUND: The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic model. METHODS: Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models. RESULTS: The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P<0.001; hazard ratio (HR), 0.348; 95% confidence interval (CI) 0.215-0.562), CA19.9 lower than median (P=0.013; HR, 0.574; 95% CI 0.370-0.891), progression-free survival after first-line CT ≥ 6 months (P=0.027; HR, 0.633; 95% CI 0.422-0.949) and previous surgery on primary tumour (P=0.027; HR, 0.609; 95% CI 0.392-0.945). We grouped the 249 patients with complete data available into three categories according to the number of fulfilled risk factors: median OS times for good-risk (zero to one factors), intermediate-risk (two factors) and poor-risk (three to four factors) groups were 13.1, 6.6 and 3.7 months, respectively (P<0.001). CONCLUSIONS: Easily available clinical and laboratory factors predict prognosis of aBTC patients undergoing second-line CT. This model allows individual patient-risk stratification and may help in treatment decision and trial design.","Source":"PubMed","category":"HUMAN","training_data":"Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer BACKGROUND: The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic model. METHODS: Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models. RESULTS: The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P<0.001; hazard ratio (HR), 0.348; 95% confidence interval (CI) 0.215-0.562), CA19.9 lower than median (P=0.013; HR, 0.574; 95% CI 0.370-0.891), progression-free survival after first-line CT ≥ 6 months (P=0.027; HR, 0.633; 95% CI 0.422-0.949) and previous surgery on primary tumour (P=0.027; HR, 0.609; 95% CI 0.392-0.945). We grouped the 249 patients with complete data available into three categories according to the number of fulfilled risk factors: median OS times for good-risk (zero to one factors), intermediate-risk (two factors) and poor-risk (three to four factors) groups were 13.1, 6.6 and 3.7 months, respectively (P<0.001). CONCLUSIONS: Easily available clinical and laboratory factors predict prognosis of aBTC patients undergoing second-line CT. This model allows individual patient-risk stratification and may help in treatment decision and trial design. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance nuclear hepatoma derived growth factor expression gallbladder cancer aim assess expression nuclear hepatoma derived growth factor hdgf benign malignant gallbladder lesions determine clinicopathological significance methods studied 40 patients gallbladder cancer gbc control group 40 patients cholelithiasis diagnoses gbc cholelithiasis confirmed histopathological examination surgery none patients received chemotherapy radiotherapy surgery tissue samples fixed 4 formalin immediately removal embedded paraffin immunohistochemical staining hdgf expression gbc cholelithiasis specimens examined immunohistochemical staining relationship hdgf expression clinicopathological parameters gbc analyzed results nuclear hdgf expression significantly higher 77 5 gbc chronic cholelithiasis 21 5 p 0 001 high nuclear hdgf levels associated histopathological subtype p 0 05 clinical stage p 0 01 perineural invasion p 0 01 sex age history gallstones lymph node metastasis univariate kaplan meier analysis showed positive nuclear hdgf expression associated decreased overall survival p 0 01 multivariate cox regression analysis showed nuclear hdgf expression lymph node metastasis independent risk factors disease free survival conclusion expression nuclear hdgf might closely related carcinogenesis clinical biological behaviors prognosis gallbladder adenocarcinoma pubmed","probabilities":0.7966102,"Title":"Prognostic significance of nuclear hepatoma-derived growth factor expression in gallbladder cancer","Abstract":"AIM: To assess the expression of nuclear hepatoma-derived growth factor (HDGF) in benign and malignant gallbladder lesions and to determine its clinicopathological significance. METHODS: We studied 40 patients with gallbladder cancer (GBC) and a control group of 40 patients with cholelithiasis. All diagnoses of GBC and cholelithiasis were confirmed by histopathological examination after surgery. None of the patients received chemotherapy or radiotherapy before surgery. All tissue samples were fixed in 4% formalin immediately after removal and embedded in paraffin for immunohistochemical staining. The HDGF expression in the GBC and cholelithiasis specimens was examined by immunohistochemical staining. The relationship between the HDGF expression and the clinicopathological parameters of GBC was analyzed. RESULTS: Nuclear HDGF expression was significantly higher (77.5%) in GBC than in chronic cholelithiasis (21.5%, P < 0.001). High nuclear HDGF levels were associated with histopathological subtype (P < 0.05), clinical stage (P < 0.01), and perineural invasion (P < 0.01) but not with sex, age, history of gallstones, or lymph node metastasis. A univariate Kaplan-Meier analysis showed that positive nuclear HDGF expression was associated with decreased overall survival (P < 0.01). Multivariate Cox regression analysis showed that nuclear HDGF expression and lymph node metastasis were independent risk factors for disease-free survival. CONCLUSION: The expression of nuclear HDGF might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of nuclear hepatoma-derived growth factor expression in gallbladder cancer AIM: To assess the expression of nuclear hepatoma-derived growth factor (HDGF) in benign and malignant gallbladder lesions and to determine its clinicopathological significance. METHODS: We studied 40 patients with gallbladder cancer (GBC) and a control group of 40 patients with cholelithiasis. All diagnoses of GBC and cholelithiasis were confirmed by histopathological examination after surgery. None of the patients received chemotherapy or radiotherapy before surgery. All tissue samples were fixed in 4% formalin immediately after removal and embedded in paraffin for immunohistochemical staining. The HDGF expression in the GBC and cholelithiasis specimens was examined by immunohistochemical staining. The relationship between the HDGF expression and the clinicopathological parameters of GBC was analyzed. RESULTS: Nuclear HDGF expression was significantly higher (77.5%) in GBC than in chronic cholelithiasis (21.5%, P < 0.001). High nuclear HDGF levels were associated with histopathological subtype (P < 0.05), clinical stage (P < 0.01), and perineural invasion (P < 0.01) but not with sex, age, history of gallstones, or lymph node metastasis. A univariate Kaplan-Meier analysis showed that positive nuclear HDGF expression was associated with decreased overall survival (P < 0.01). Multivariate Cox regression analysis showed that nuclear HDGF expression and lymph node metastasis were independent risk factors for disease-free survival. CONCLUSION: The expression of nuclear HDGF might be closely related to the carcinogenesis, clinical biological behaviors, and prognosis of gallbladder adenocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact intraoperative blood transfusion short long term outcomes curative hepatectomy intrahepatic cholangiocarcinoma propensity score matching analysis afc ihcc study group background impact intraoperative blood transfusion ibt outcomes following intrahepatic cholangiocarcinoma ihcc resection remains ascertained methods consecutive ihcc resected analyzed first cohort n 569 used investigating short term outcomes morbidity mortality second cohort n 522 excluding patients dead within 90 days surgery analyzed exploring overall survival os disease free survival dfs patients received ibt compared using propensity score matching psm method results among 569 patients 90 day morbidity mortality rates 47 n 269 8 n 47 psm 208 patients matched association ibt increased overall morbidity severe morbidity p 0 010 however ibt impact 90 day mortality rate p 0 999 regarding long term outcomes analysis second cohort n 522 5 year os dfs rates 39 25 using psm 196 patients matched association ibt os dfs found p 0 333 p 0 491 conclusions ibt associated increased risk morbidity impact long term outcomes need ibt considered surrogate advanced disease requiring complex resection still restricted transfusion policy remain advocated ihcc resection pubmed","probabilities":0.9799733,"Title":"Impact of intraoperative blood transfusion on short and long term outcomes after curative hepatectomy for intrahepatic cholangiocarcinoma: a propensity score matching analysis by the AFC-IHCC study group","Abstract":"BACKGROUND: The impact of intraoperative blood transfusion (IBT) on outcomes following intrahepatic cholangiocarcinoma (IHCC) resection remains to be ascertained. METHODS: All consecutive IHCC resected were analyzed. A first cohort (n = 569) was used for investigating short-term outcomes (morbidity and mortality). A second cohort (n = 522) excluding patients dead within 90 days of surgery was analyzed for exploring overall survival (OS) and disease free survival (DFS). Patients who received IBT were compared to those who did not, after using a propensity score matching (PSM) method. RESULTS: Among 569 patients, 90-day morbidity and mortality rates were 47% (n = 269) and 8% (n = 47). After PSM, 208 patients were matched. There was an association between IBT and increased overall morbidity and severe morbidity (p = 0.010). However, IBT did not impact 90-day mortality rate (p > 0.999). Regarding long-term outcomes analysis in the second cohort (n = 522), 5-year OS and DFS rates were 39% and 25%. Using PSM, 196 patients were matched and no association between IBT and OS or DFS was found (p = 0.333 and p = 0.491). CONCLUSIONS: IBT is associated with an increased risk of morbidity but does not impact on long-term outcomes. Need for IBT should be considered as a surrogate of advanced disease requiring complex resection. Still, restricted transfusion policy should remain advocated for IHCC resection.","Source":"PubMed","category":"HUMAN","training_data":"Impact of intraoperative blood transfusion on short and long term outcomes after curative hepatectomy for intrahepatic cholangiocarcinoma: a propensity score matching analysis by the AFC-IHCC study group BACKGROUND: The impact of intraoperative blood transfusion (IBT) on outcomes following intrahepatic cholangiocarcinoma (IHCC) resection remains to be ascertained. METHODS: All consecutive IHCC resected were analyzed. A first cohort (n = 569) was used for investigating short-term outcomes (morbidity and mortality). A second cohort (n = 522) excluding patients dead within 90 days of surgery was analyzed for exploring overall survival (OS) and disease free survival (DFS). Patients who received IBT were compared to those who did not, after using a propensity score matching (PSM) method. RESULTS: Among 569 patients, 90-day morbidity and mortality rates were 47% (n = 269) and 8% (n = 47). After PSM, 208 patients were matched. There was an association between IBT and increased overall morbidity and severe morbidity (p = 0.010). However, IBT did not impact 90-day mortality rate (p > 0.999). Regarding long-term outcomes analysis in the second cohort (n = 522), 5-year OS and DFS rates were 39% and 25%. Using PSM, 196 patients were matched and no association between IBT and OS or DFS was found (p = 0.333 and p = 0.491). CONCLUSIONS: IBT is associated with an increased risk of morbidity but does not impact on long-term outcomes. Need for IBT should be considered as a surrogate of advanced disease requiring complex resection. Still, restricted transfusion policy should remain advocated for IHCC resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association adjuvant chemoradiotherapy survival patients resected gallbladder carcinoma systematic review meta analysis background impact adjuvant radiotherapy art survival gallbladder carcinoma gbc remains underexplored conflicting results reported systematic review meta analysis performed clarify impact art gbc methods systematic literature search several databases performed following preferred reporting items systematic reviews meta analyses prisma guidelines inception august 2016 studies reported survival outcomes patients without art curative surgery included results inclusion criteria met 14 retrospective studies including 9364 analyzable patients studies moderate risk bias generally art group patients unfavorable characteristics group surgery alone nevertheless pooled results showed art significantly reduced risk death hazard ratio hr 0 54 95 confidence interval ci 0 44 0 67 p 0 001 recurrence hr 0 61 95 ci 0 38 0 98 p 0 04 gbc compared surgery alone exploratory analyses demonstrated survival benefit art subgroup patients lymph node positive diseases hr 0 61 p 0 001 r1 resections hr 0 55 p 0 001 patients lymph node negative disease hr 1 06 p 0 78 evidence publication bias found p 0 663 conclusions study first meta analysis evaluate role art provide supporting evidence art may offer survival benefits especially high risk patients however confirmation randomized prospective study needed clarify subgroup gbc patients benefit art stn","probabilities":0.9799733,"Title":"Association Of Adjuvant Chemoradiotherapy With Survival In Patients With Resected Gallbladder Carcinoma: A Systematic Review And Meta-Analysis","Abstract":"Background: The impact of adjuvant radiotherapy (ART) on survival from gallbladder carcinoma (GBC) remains underexplored, with conflicting results reported. A systematic review and meta-analysis was performed to clarify the impact of ART in GBC. \r\n\r\n Methods: A systematic literature search of several databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, from inception to August 2016. Studies that reported survival outcomes for patients with or without ART after curative surgery were included. \r\n\r\n Results: All the inclusion criteria was met by 14 retrospective studies including 9364 analyzable patients, but most of the studies had a moderate risk of bias. Generally, the ART group had more patients with unfavorable characteristics than the group that had surgery alone. Nevertheless, the pooled results showed that ART significantly reduced the risk of death (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.44-0.67; p < 0.001) and recurrence (HR 0.61; 95% CI 0.38-0.98; p = 0.04) of GBC compared with surgery alone. Exploratory analyses demonstrated a survival benefit from ART for a subgroup of patients with lymph node-positive diseases (HR 0.61; p < 0.001) and R1 resections (HR 0.55; p < 0.001), but not for patients with lymph node-negative disease (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663). \r\n\r\n Conclusions: This study is the first meta-analysis to evaluate the role of ART and to provide supporting evidence that ART may offer survival benefits, especially for high-risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would benefit most from ART.","Source":"STN","category":"HUMAN","training_data":"Association Of Adjuvant Chemoradiotherapy With Survival In Patients With Resected Gallbladder Carcinoma: A Systematic Review And Meta-Analysis Background: The impact of adjuvant radiotherapy (ART) on survival from gallbladder carcinoma (GBC) remains underexplored, with conflicting results reported. A systematic review and meta-analysis was performed to clarify the impact of ART in GBC. \r\n\r\n Methods: A systematic literature search of several databases was performed following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, from inception to August 2016. Studies that reported survival outcomes for patients with or without ART after curative surgery were included. \r\n\r\n Results: All the inclusion criteria was met by 14 retrospective studies including 9364 analyzable patients, but most of the studies had a moderate risk of bias. Generally, the ART group had more patients with unfavorable characteristics than the group that had surgery alone. Nevertheless, the pooled results showed that ART significantly reduced the risk of death (hazard ratio [HR], 0.54; 95% confidence interval [CI] 0.44-0.67; p < 0.001) and recurrence (HR 0.61; 95% CI 0.38-0.98; p = 0.04) of GBC compared with surgery alone. Exploratory analyses demonstrated a survival benefit from ART for a subgroup of patients with lymph node-positive diseases (HR 0.61; p < 0.001) and R1 resections (HR 0.55; p < 0.001), but not for patients with lymph node-negative disease (HR 1.06; p = 0.78). No evidence of publication bias was found (p = 0.663). \r\n\r\n Conclusions: This study is the first meta-analysis to evaluate the role of ART and to provide supporting evidence that ART may offer survival benefits, especially for high-risk patients. However, further confirmation with a randomized prospective study is needed to clarify the subgroup of GBC patients who would benefit most from ART. STN","prediction_labels":"HUMAN"},{"cleaned":"serum tumor markers bile duct cancer review context bile duct cancer bdc disease grave prognosis often diagnosed late objective aim review evaluate available literature tumor markers serum patients bdc methods using search words serum markers bile duct cancer cholangiocarcinoma biomarker tumor marker search carried results seventy five studies included review conclusion ca19 9 far studied promising diagnostic prognostic marker bdc also different mucins interesting new markers bdc serum pubmed","probabilities":0.9799733,"Title":"Serum tumor markers in bile duct cancer--a review","Abstract":"CONTEXT: Bile duct cancer (BDC) is a disease with a very grave prognosis, often diagnosed too late. OBJECTIVE: The aim of this review is to evaluate available literature on tumor markers in serum from patients with BDC. METHODS: Using the search words \"serum markers\", \"bile duct cancer\", \"cholangiocarcinoma\", \"biomarker\" and \"tumor marker\", a search was carried out. RESULTS: Seventy-five studies were included in the review. CONCLUSION: CA19-9 is by far the most studied and most promising diagnostic and/or prognostic marker in BDC. But also the different mucins are interesting as new markers of BDC in serum.","Source":"PubMed","category":"HUMAN","training_data":"Serum tumor markers in bile duct cancer--a review CONTEXT: Bile duct cancer (BDC) is a disease with a very grave prognosis, often diagnosed too late. OBJECTIVE: The aim of this review is to evaluate available literature on tumor markers in serum from patients with BDC. METHODS: Using the search words \"serum markers\", \"bile duct cancer\", \"cholangiocarcinoma\", \"biomarker\" and \"tumor marker\", a search was carried out. RESULTS: Seventy-five studies were included in the review. CONCLUSION: CA19-9 is by far the most studied and most promising diagnostic and/or prognostic marker in BDC. But also the different mucins are interesting as new markers of BDC in serum. PubMed","prediction_labels":"HUMAN"},{"cleaned":"defining benefit adjuvant therapy following resection intrahepatic cholangiocarcinoma background intrahepatic cholangiocarcinoma icc rare increasing incidence hepatectomy curative benefit adjuvant therapy remains unclear utilized national cancer data base ncdb isolate predictors overall survival describe national pattern administration identify characteristics patients experience survival benefit following resection icc methods patients diagnosed icc 1998 2006 underwent surgical resection identified ncdb kaplan meier cox regression analyses evaluated differences overall survival patients received results overall 638 patients underwent surgery icc identified multivariate cox regression analysis identified positive lymph nodes unexamined lymph nodes positive margins lack predictors decreased overall survival 28 1 patients positive margins 20 1 positive nodes patients well younger fewer co morbid conditions likely receive adjusting prognostic variables patients found significantly benefit positive lymph nodes chemotherapy hazard ratio hr 0 54 p 0 0365 chemoradiation hr 0 50 p 0 005 positive margins chemotherapy hr 0 44 p 0 0016 chemoradiation hr 0 57 p 0 0039 conclusions positive lymph nodes positive margins associated poor survival resection icc controlling prognostic factors associated significant survival benefits among patients positive nodes positive margins pubmed","probabilities":0.9799733,"Title":"Defining the Benefit of Adjuvant Therapy Following Resection for Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is rare but is increasing in incidence. While hepatectomy can be curative, the benefit of adjuvant therapy (AT) remains unclear. We utilized the National Cancer Data Base (NCDB) to isolate predictors of overall survival, describe the national pattern of AT administration, and identify characteristics of patients who experience a survival benefit from AT following resection for ICC. METHODS: Patients who were diagnosed with ICC between 1998 and 2006 and underwent surgical resection were identified through the NCDB. Kaplan-Meier and Cox regression analyses evaluated differences in overall survival between patients who received AT and those who did not. RESULTS: Overall, 638 patients who underwent surgery for ICC were identified. Multivariate Cox regression analysis identified positive lymph nodes, unexamined lymph nodes, positive margins, and lack of AT as predictors of decreased overall survival; 28.1 % of patients had positive margins while 20.1 % had positive nodes. These patients, as well as those who were younger and had fewer co-morbid conditions, were most likely to receive AT. After adjusting for other prognostic variables, patients were found to significantly benefit from AT if they had positive lymph nodes [chemotherapy: hazard ratio (HR) 0.54, p = 0.0365; chemoradiation: HR 0.50, p = 0.005] or positive margins (chemotherapy: HR 0.44, p = 0.0016; chemoradiation: HR 0.57, p = 0.0039). CONCLUSIONS: Positive lymph nodes and positive margins were associated with poor survival after resection for ICC. After controlling for other prognostic factors, AT was associated with significant survival benefits among patients with positive nodes or positive margins.","Source":"PubMed","category":"HUMAN","training_data":"Defining the Benefit of Adjuvant Therapy Following Resection for Intrahepatic Cholangiocarcinoma BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is rare but is increasing in incidence. While hepatectomy can be curative, the benefit of adjuvant therapy (AT) remains unclear. We utilized the National Cancer Data Base (NCDB) to isolate predictors of overall survival, describe the national pattern of AT administration, and identify characteristics of patients who experience a survival benefit from AT following resection for ICC. METHODS: Patients who were diagnosed with ICC between 1998 and 2006 and underwent surgical resection were identified through the NCDB. Kaplan-Meier and Cox regression analyses evaluated differences in overall survival between patients who received AT and those who did not. RESULTS: Overall, 638 patients who underwent surgery for ICC were identified. Multivariate Cox regression analysis identified positive lymph nodes, unexamined lymph nodes, positive margins, and lack of AT as predictors of decreased overall survival; 28.1 % of patients had positive margins while 20.1 % had positive nodes. These patients, as well as those who were younger and had fewer co-morbid conditions, were most likely to receive AT. After adjusting for other prognostic variables, patients were found to significantly benefit from AT if they had positive lymph nodes [chemotherapy: hazard ratio (HR) 0.54, p = 0.0365; chemoradiation: HR 0.50, p = 0.005] or positive margins (chemotherapy: HR 0.44, p = 0.0016; chemoradiation: HR 0.57, p = 0.0039). CONCLUSIONS: Positive lymph nodes and positive margins were associated with poor survival after resection for ICC. After controlling for other prognostic factors, AT was associated with significant survival benefits among patients with positive nodes or positive margins. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic biomarkers patients resected cholangiocarcinoma systematic review meta analysis purpose biomarkers patients resected cholangiocarcinoma cc improve staging may ultimately result personalized medicine studies evaluating biomarkers often shown inconsistent results performed systematic review meta analysis investigate prognostic value immunohistochemistry based markers evaluated patients resected cc methods july 2013 searched two main medical literature databases medline embase extracted hazard ratios hrs associated 95 confidence intervals cis identified studies performed random effects model meta analyses overall survival os accordance preferred reporting items systematic reviews meta analyses statement reporting recommendations tumor marker prognostic studies remark guidelines results total 73 studies including 4 126 patients studying 77 individual biomarkers met inclusion criteria fourteen studies graded low risk bias biomarkers prognostic os pooled analysis included fascin hr 2 58 95 ci 1 19 5 58 egfr hr 1 79 95 ci 1 14 2 8 muc1 hr 2 52 95 ci 1 49 4 26 muc4 hr 2 45 95 ci 1 56 3 86 p27 hr 0 29 95 ci 0 14 0 6 markers showed promising results single studies including hsp27 akt hdgf muc6 p16 p 4ebp1 s100a4 sma keratin 903 trop2 conclusions meta analysis demonstrated biomarkers fascin egfr muc1 muc4 p27 associated survival patients resected cc future studies validate promising biomarkers adhere remark guidelines pubmed","probabilities":0.9799733,"Title":"Prognostic biomarkers in patients with resected cholangiocarcinoma: a systematic review and meta-analysis","Abstract":"PURPOSE: Biomarkers for patients with resected cholangiocarcinoma (CC) can improve staging and may ultimately result in personalized medicine. Studies evaluating these biomarkers often have shown inconsistent results. We performed a systematic review and meta-analysis to investigate the prognostic value of all immunohistochemistry-based markers that have been evaluated in patients with resected CC. METHODS: In July 2013, we searched the two main medical literature databases: MEDLINE and EMBASE. We extracted hazard ratios (HRs) and associated 95% confidence intervals (CIs) from the identified studies and performed random-effects model meta-analyses on overall survival (OS) in accordance with preferred reporting items for systematic reviews and meta-analyses statement and reporting recommendations for tumor marker prognostic studies (REMARK) guidelines. RESULTS: A total of 73 studies, including 4,126 patients studying 77 individual biomarkers, met the inclusion criteria. Fourteen studies were graded with a low risk of bias. Biomarkers prognostic of OS in pooled analysis included fascin (HR 2.58; 95% CI 1.19-5.58), EGFR (HR 1.79; 95% CI 1.14-2.8), MUC1 (HR 2.52; 95% CI 1.49-4.26), MUC4 (HR 2.45; 95% CI 1.56-3.86), and p27 (HR 0.29; 95% CI 0.14-0.6). Other markers showed promising results in single studies, including HSP27, Akt, HDGF, MUC6, p16, p-4EBP1, S100A4, α-SMA, Keratin 903, and TROP2. CONCLUSIONS: Meta-analysis demonstrated that the biomarkers fascin, EGFR, MUC1, MUC4, and p27 are associated with survival in patients with resected CC. Future studies should validate these, and other promising biomarkers, and adhere to the REMARK guidelines.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic biomarkers in patients with resected cholangiocarcinoma: a systematic review and meta-analysis PURPOSE: Biomarkers for patients with resected cholangiocarcinoma (CC) can improve staging and may ultimately result in personalized medicine. Studies evaluating these biomarkers often have shown inconsistent results. We performed a systematic review and meta-analysis to investigate the prognostic value of all immunohistochemistry-based markers that have been evaluated in patients with resected CC. METHODS: In July 2013, we searched the two main medical literature databases: MEDLINE and EMBASE. We extracted hazard ratios (HRs) and associated 95% confidence intervals (CIs) from the identified studies and performed random-effects model meta-analyses on overall survival (OS) in accordance with preferred reporting items for systematic reviews and meta-analyses statement and reporting recommendations for tumor marker prognostic studies (REMARK) guidelines. RESULTS: A total of 73 studies, including 4,126 patients studying 77 individual biomarkers, met the inclusion criteria. Fourteen studies were graded with a low risk of bias. Biomarkers prognostic of OS in pooled analysis included fascin (HR 2.58; 95% CI 1.19-5.58), EGFR (HR 1.79; 95% CI 1.14-2.8), MUC1 (HR 2.52; 95% CI 1.49-4.26), MUC4 (HR 2.45; 95% CI 1.56-3.86), and p27 (HR 0.29; 95% CI 0.14-0.6). Other markers showed promising results in single studies, including HSP27, Akt, HDGF, MUC6, p16, p-4EBP1, S100A4, α-SMA, Keratin 903, and TROP2. CONCLUSIONS: Meta-analysis demonstrated that the biomarkers fascin, EGFR, MUC1, MUC4, and p27 are associated with survival in patients with resected CC. Future studies should validate these, and other promising biomarkers, and adhere to the REMARK guidelines. PubMed","prediction_labels":"HUMAN"},{"cleaned":"identification lifr pik3r1 mmp12 novel prognostic signatures gallbladder cancer using network based module analysis background gallbladder cancer gbc rare aggressive malignancy biliary tract dismal survival rate effective biomarkers therapeutic targets urgently needed methods analyzed gene expression profiles gbc identify differentially expressed genes degs used degs identify functional module biomarkers based protein functional interaction fi networks evaluated module gene protein expression clinical significance immunohistochemistry staining ihc tissue microarray tma 80 gbc samples results five functional modules identified module 0 included classical cancer signaling pathways ras pi3k akt modules 1 4 included genes associated muscle cells fibrinogen extracellular matrix integrins respectively validated expression lifr pik3r1 mmp12 hubs functional nodes modules compared paired peritumoural tissues found expression lifr p 0 002 pik3r1 p 0 046 proteins significantly downregulated mmp12 p 0 006 significantly upregulated prognostic analysis showed patients low expression lifr shorter overall survival high expression log rank test p 0 028 trend pik3r1 p 0 053 mmp12 p 0 006 multivariate analysis indicated expression mmp12 protein hazard ratio hr 0 429 95 confidence interval ci 0 198 0 930 p 0 032 one significant independent prognostic factors overall survival conclusions found highly reliable fi network revealed lifr pik3r1 mmp12 novel prognostic biomarker candidates gbc findings accelerate biomarker discovery therapeutic development cancer stn","probabilities":0.9285714,"Title":"Identification Of Lifr Pik3R1 And Mmp12 As Novel Prognostic Signatures In Gallbladder Cancer Using Network-Based Module Analysis","Abstract":"Background: Gallbladder cancer (GBC) is a rare and aggressive malignancy of the biliary tract with a dismal survival rate. Effective biomarkers and therapeutic targets are urgently needed. Methods: We analyzed gene expression profiles of GBC to identify differentially expressed genes (DEGs) and then used these DEGs to identify functional module biomarkers based on protein functional interaction (FI) networks. We further evaluated the module-gene protein expression and clinical significance with immunohistochemistry staining (IHC) in a tissue microarray (TMA) from 80 GBC samples. Results: Five functional modules were identified. Module 0 included classical cancer signaling pathways, such as Ras and PI3K-Akt; and modules 1-4 included genes associated with muscle cells, fibrinogen, extracellular matrix, and integrins, respectively. We validated the expression of LIFR, PIK3R1, and MMP12, which were hubs or functional nodes in modules. Compared with paired peritumoural tissues, we found that the expression of LIFR (P = 0.002) and PIK3R1 (P = 0.046) proteins were significantly downregulated, and MMP12 (P = 0.006) was significantly upregulated. Further prognostic analysis showed that patients with low expression of LIFR had shorter overall survival than those with high expression (log-rank test P = 0.028), the same trend as for PIK3R1 (P = 0.053) and MMP12 (P = 0.006). Multivariate analysis indicated that expression of MMP12 protein (hazard ratio [HR] = 0.429; 95% confidence interval [CI] 0.198, 0.930; P = 0.032) was one of the significant independent prognostic factors for overall survival. Conclusions: We found a highly reliable FI network, which revealed LIFR, PIK3R1, and MMP12 as novel prognostic biomarker candidates for GBC. These findings could accelerate biomarker discovery and therapeutic development in this cancer.","Source":"STN","category":"ANIMAL","training_data":"Identification Of Lifr Pik3R1 And Mmp12 As Novel Prognostic Signatures In Gallbladder Cancer Using Network-Based Module Analysis Background: Gallbladder cancer (GBC) is a rare and aggressive malignancy of the biliary tract with a dismal survival rate. Effective biomarkers and therapeutic targets are urgently needed. Methods: We analyzed gene expression profiles of GBC to identify differentially expressed genes (DEGs) and then used these DEGs to identify functional module biomarkers based on protein functional interaction (FI) networks. We further evaluated the module-gene protein expression and clinical significance with immunohistochemistry staining (IHC) in a tissue microarray (TMA) from 80 GBC samples. Results: Five functional modules were identified. Module 0 included classical cancer signaling pathways, such as Ras and PI3K-Akt; and modules 1-4 included genes associated with muscle cells, fibrinogen, extracellular matrix, and integrins, respectively. We validated the expression of LIFR, PIK3R1, and MMP12, which were hubs or functional nodes in modules. Compared with paired peritumoural tissues, we found that the expression of LIFR (P = 0.002) and PIK3R1 (P = 0.046) proteins were significantly downregulated, and MMP12 (P = 0.006) was significantly upregulated. Further prognostic analysis showed that patients with low expression of LIFR had shorter overall survival than those with high expression (log-rank test P = 0.028), the same trend as for PIK3R1 (P = 0.053) and MMP12 (P = 0.006). Multivariate analysis indicated that expression of MMP12 protein (hazard ratio [HR] = 0.429; 95% confidence interval [CI] 0.198, 0.930; P = 0.032) was one of the significant independent prognostic factors for overall survival. Conclusions: We found a highly reliable FI network, which revealed LIFR, PIK3R1, and MMP12 as novel prognostic biomarker candidates for GBC. These findings could accelerate biomarker discovery and therapeutic development in this cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"identification calmodulin binding domains fas death receptor extrinsic apoptotic pathway initiated binding fas ligand ectodomain surface death receptor fas protein subsequently intracellular death domain fas fasdd fas associated protein fadd interact form core death inducing signaling complex disc crucial step activation caspases induce cell death previous studies shown calmodulin cam recruited disc cholangiocarcinoma cells specifically interacts fasdd regulate apoptotic survival signaling pathway inhibition cam activity disc stimulates apoptosis significantly recently shown cam forms ternary complex fasdd 2 1 cam fasdd however molecular mechanism cam binds two distinct fasdd motifs fully understood employed mass spectrometry nuclear magnetic resonance nmr biophysical biochemical methods identify binding regions fasdd provide molecular basis role cam fas mediated apoptosis proteolytic digestion mass spectrometry data revealed peptides spanning residues 209 239 fas pep1 251 288 fas pep2 constitute two cam binding regions fasdd determine molecular mechanism interaction characterized binding recombinant synthetic fas pep1 fas pep2 peptides cam data show peptides engage n c terminal lobes cam simultaneously binding fas pep1 cam entropically driven fas pep2 cam enthalpically driven indicating combination electrostatic hydrophobic forces contribute stabilization fasdd cam complex data suggest fas pep1 fas pep2 involved extensive intermolecular contacts death domain fadd binding cam regions may hinder ability bind fadd thus greatly inhibiting initiation apoptotic signaling pathway stn","probabilities":0.9467213,"Title":"Identification Of The Calmodulin-Binding Domains Of Fas Death Receptor","Abstract":"The extrinsic apoptotic pathway is initiated by binding of a Fas ligand to the ectodomain of the surface death receptor Fas protein. Subsequently, the intracellular death domain of Fas (FasDD) and that of the Fas-associated protein (FADD) interact to form the core of the death-inducing signaling complex (DISC), a crucial step for activation of caspases that induce cell death. Previous studies have shown that calmodulin (CaM) is recruited into the DISC in cholangiocarcinoma cells and specifically interacts with FasDD to regulate the apoptotic/survival signaling pathway. Inhibition of CaM activity in DISC stimulates apoptosis significantly. We have recently shown that CaM forms a ternary complex with FasDD (2:1 CaM:FasDD). However, the molecular mechanism by which CaM binds to two distinct FasDD motifs is not fully understood. Here, we employed mass spectrometry, nuclear magnetic resonance (NMR), biophysical, and biochemical methods to identify the binding regions of FasDD and provide a molecular basis for the role of CaM in Fas-mediated apoptosis. Proteolytic digestion and mass spectrometry data revealed that peptides spanning residues 209-239 (Fas-Pep1) and 251-288 (Fas-Pep2) constitute the two CaM-binding regions of FasDD. To determine the molecular mechanism of interaction, we have characterized the binding of recombinant/synthetic Fas-Pep1 and Fas-Pep2 peptides with CaM. Our data show that both peptides engage the N- and C-terminal lobes of CaM simultaneously. Binding of Fas-Pep1 to CaM is entropically driven while that of Fas-Pep2 to CaM is enthalpically driven, indicating that a combination of electrostatic and hydrophobic forces contribute to the stabilization of the FasDD-CaM complex. Our data suggest that because Fas-Pep1 and Fas-Pep2 are involved in extensive intermolecular contacts with the death domain of FADD, binding of CaM to these regions may hinder its ability to bind to FADD, thus greatly inhibiting the initiation of apoptotic signaling pathway.","Source":"STN","category":"ANIMAL","training_data":"Identification Of The Calmodulin-Binding Domains Of Fas Death Receptor The extrinsic apoptotic pathway is initiated by binding of a Fas ligand to the ectodomain of the surface death receptor Fas protein. Subsequently, the intracellular death domain of Fas (FasDD) and that of the Fas-associated protein (FADD) interact to form the core of the death-inducing signaling complex (DISC), a crucial step for activation of caspases that induce cell death. Previous studies have shown that calmodulin (CaM) is recruited into the DISC in cholangiocarcinoma cells and specifically interacts with FasDD to regulate the apoptotic/survival signaling pathway. Inhibition of CaM activity in DISC stimulates apoptosis significantly. We have recently shown that CaM forms a ternary complex with FasDD (2:1 CaM:FasDD). However, the molecular mechanism by which CaM binds to two distinct FasDD motifs is not fully understood. Here, we employed mass spectrometry, nuclear magnetic resonance (NMR), biophysical, and biochemical methods to identify the binding regions of FasDD and provide a molecular basis for the role of CaM in Fas-mediated apoptosis. Proteolytic digestion and mass spectrometry data revealed that peptides spanning residues 209-239 (Fas-Pep1) and 251-288 (Fas-Pep2) constitute the two CaM-binding regions of FasDD. To determine the molecular mechanism of interaction, we have characterized the binding of recombinant/synthetic Fas-Pep1 and Fas-Pep2 peptides with CaM. Our data show that both peptides engage the N- and C-terminal lobes of CaM simultaneously. Binding of Fas-Pep1 to CaM is entropically driven while that of Fas-Pep2 to CaM is enthalpically driven, indicating that a combination of electrostatic and hydrophobic forces contribute to the stabilization of the FasDD-CaM complex. Our data suggest that because Fas-Pep1 and Fas-Pep2 are involved in extensive intermolecular contacts with the death domain of FADD, binding of CaM to these regions may hinder its ability to bind to FADD, thus greatly inhibiting the initiation of apoptotic signaling pathway. STN","prediction_labels":"ANIMAL"},{"cleaned":"six microrna set prognostic indicators bile duct cancer micrornas mirnas play important roles cancer progression altering transcriptional control purpose study identify explore specific mirnas prognostic predictive biomarkers bile duct cancer bdc analyzing next generation data mirna expression profiles corresponding clinical information bdc samples extracted cancer genome atlas tcga differentially expressed mirnas determined samr package r software target genes mirnas predicted targetscan functional enrichment analysis hypergeometric test analysis target genes performed diagnosis accuracy mirnas judged roc curves analysis total 120 differentially expressed mirnas obtained six important mirnas selected predicted prognosis predicting biomarkers bdc besides functional analysis showed enriched pathways significantly related ion binding might involve carcinogenesis bdc moreover top 3 important pathways sharing influence noted results demonstrated hsa mir 483 5p hsa mir 675 hsa mir 139 3p hsa mir 598 hsa mir 625 hsa mir 187 serve prognostic predictive markers survival bdc patients potentially provided targets future therapy stn","probabilities":0.9799733,"Title":"A Six-Microrna Set As Prognostic Indicators For Bile Duct Cancer","Abstract":"MicroRNAs (miRNAs) play important roles in cancer progression by altering transcriptional control. The purpose of this study is to identify and explore specific miRNAs as prognostic and predictive biomarkers for bile duct cancer (BDC) by analyzing Next-generation data. miRNA expression profiles and corresponding clinical information of BDC samples were extracted from The Cancer Genome Atlas (TCGA). The differentially expressed miRNAs were determined by SAMR package in R software. Target genes of those miRNAs were predicted by Targetscan. Functional enrichment analysis and hypergeometric test analysis of target genes were performed. Then, diagnosis accuracy of miRNAs was judged by ROC Curves analysis. Total 120 differentially expressed miRNAs were obtained, of which six important miRNAs were selected and predicted as prognosis and predicting biomarkers in BDC. Besides, functional analysis showed that both enriched pathways were significantly related with ion binding, which might involve in the carcinogenesis of BDC. Moreover, top 3 important pathways sharing the most influence were noted. Our results demonstrated that hsa-miR-483-5p, hsa-miR-675, hsa-miR-139-3p, hsa-miR-598, hsa-miR-625 and hsa-miR-187 could serve as prognostic and predictive markers for survival of BDC patients and could potentially be provided as targets for future therapy.","Source":"STN","category":"HUMAN","training_data":"A Six-Microrna Set As Prognostic Indicators For Bile Duct Cancer MicroRNAs (miRNAs) play important roles in cancer progression by altering transcriptional control. The purpose of this study is to identify and explore specific miRNAs as prognostic and predictive biomarkers for bile duct cancer (BDC) by analyzing Next-generation data. miRNA expression profiles and corresponding clinical information of BDC samples were extracted from The Cancer Genome Atlas (TCGA). The differentially expressed miRNAs were determined by SAMR package in R software. Target genes of those miRNAs were predicted by Targetscan. Functional enrichment analysis and hypergeometric test analysis of target genes were performed. Then, diagnosis accuracy of miRNAs was judged by ROC Curves analysis. Total 120 differentially expressed miRNAs were obtained, of which six important miRNAs were selected and predicted as prognosis and predicting biomarkers in BDC. Besides, functional analysis showed that both enriched pathways were significantly related with ion binding, which might involve in the carcinogenesis of BDC. Moreover, top 3 important pathways sharing the most influence were noted. Our results demonstrated that hsa-miR-483-5p, hsa-miR-675, hsa-miR-139-3p, hsa-miR-598, hsa-miR-625 and hsa-miR-187 could serve as prognostic and predictive markers for survival of BDC patients and could potentially be provided as targets for future therapy. STN","prediction_labels":"HUMAN"},{"cleaned":"postoperative ca19 9 change useful predictor intrahepatic cholangiocarcinoma survival following liver resection background investigate clinical significance perioperative ca19 9 change predicting survival intrahepatic cholangiocarcinoma icc patients treated surgical resection methods retrospectively reviewed data 74 icc patients treated surgical resection april 2001 july 2010 perioperative ca19 9 preoperative level postoperative lowest level level recurrence levels analyzed patient distribution survival results surgery 45 patients high preoperative ca19 9 levels 37 u ml 29 normal levels 37 u ml 45 patients high ca19 9 levels 34 normalized ca19 9 levels resection 11 persistently high levels 34 patients normalized ca19 9 levels 18 showed recurrence 29 patients normal preoperative levels 15 showed recurrence multivariate analysis presented old age hazard ratio hr 3 881 p 0 01 persistently high postoperative ca19 9 level hr 4 41 p 0 001 perineural invasion hr 3 073 p 0 01 narrow resection margin hr 3 152 p 0 05 lymph node metastasis hr 3 427 p 0 02 significant independent risk factors survival conclusions patients normalized ca19 9 levels postoperatively longer survival outcomes therefore normalized postoperative ca19 9 may useful clinical marker icc survival stn","probabilities":0.9799733,"Title":"Postoperative Ca19-9 Change Is A Useful Predictor Of Intrahepatic Cholangiocarcinoma Survival Following Liver Resection","Abstract":"Background: To investigate the clinical significance of the perioperative CA19-9 change for predicting survival in intrahepatic cholangiocarcinoma (ICC) patients treated with surgical resection. \r\n\r\n Methods: We retrospectively reviewed the data from 74 ICC patients treated with surgical resection between April 2001 and July 2010. Perioperative CA19-9 (preoperative level, postoperative lowest level, and level at recurrence) levels were analyzed for patient distribution and survival. \r\n\r\n Results: Before surgery, there were 45 patients who had high preoperative CA19-9 levels (>37 U/mL) and 29 who had normal levels (≤37 U/mL). Of 45 patients with high CA19-9 levels, 34 had normalized CA19-9 levels after resection and 11 had persistently high levels. Of 34 patients with normalized CA19-9 levels, 18 showed recurrence. Of 29 patients with normal preoperative levels, 15 showed recurrence. Multivariate analysis presented that old age (hazard ratio [HR] = 3.881, p < 0.01), persistently high postoperative CA19-9 level (HR = 4.41, p < 0.001), perineural invasion (HR = 3.073, p = 0.01), narrow resection margin (HR = 3.152, p = 0.05), and lymph node metastasis (HR = 3.427, p = 0.02) were significant independent risk factors for survival. \r\n\r\n Conclusions: Patients who have normalized CA19-9 levels postoperatively have longer survival outcomes. Therefore, normalized postoperative CA19-9 may be a useful clinical marker for ICC survival.","Source":"STN","category":"HUMAN","training_data":"Postoperative Ca19-9 Change Is A Useful Predictor Of Intrahepatic Cholangiocarcinoma Survival Following Liver Resection Background: To investigate the clinical significance of the perioperative CA19-9 change for predicting survival in intrahepatic cholangiocarcinoma (ICC) patients treated with surgical resection. \r\n\r\n Methods: We retrospectively reviewed the data from 74 ICC patients treated with surgical resection between April 2001 and July 2010. Perioperative CA19-9 (preoperative level, postoperative lowest level, and level at recurrence) levels were analyzed for patient distribution and survival. \r\n\r\n Results: Before surgery, there were 45 patients who had high preoperative CA19-9 levels (>37 U/mL) and 29 who had normal levels (≤37 U/mL). Of 45 patients with high CA19-9 levels, 34 had normalized CA19-9 levels after resection and 11 had persistently high levels. Of 34 patients with normalized CA19-9 levels, 18 showed recurrence. Of 29 patients with normal preoperative levels, 15 showed recurrence. Multivariate analysis presented that old age (hazard ratio [HR] = 3.881, p < 0.01), persistently high postoperative CA19-9 level (HR = 4.41, p < 0.001), perineural invasion (HR = 3.073, p = 0.01), narrow resection margin (HR = 3.152, p = 0.05), and lymph node metastasis (HR = 3.427, p = 0.02) were significant independent risk factors for survival. \r\n\r\n Conclusions: Patients who have normalized CA19-9 levels postoperatively have longer survival outcomes. Therefore, normalized postoperative CA19-9 may be a useful clinical marker for ICC survival. STN","prediction_labels":"HUMAN"},{"cleaned":"capecitabine plus cisplatin first line chemotherapy advanced biliary tract cancer retrospective single center study background palliative chemotherapy currently primary therapeutic approach treatment advanced biliary tract cancer btc aim assess efficacy safety capecitabine plus cisplatin first line chemotherapy patients advanced btc analyze relationship level ca19 9 clinical outcome methods retrospectively reviewed records patients unresectable metastatic recurrent btc treated capecitabine plus cisplatin capecitabine administered orally dose 1 000 mg m 2 twice day 14 days followed 1 week rest period cisplatin administered intravenously days 1 8 dose 30 mg m 2 60 min every 3 weeks results total 176 patients enrolled among 143 assessable patients 24 17 partial response complete response radiologically confirmed 1 patient gallbladder cancer sixty two patients 43 stable disease 56 patients 39 progressive disease median follow 5 7 months median time progression ttp 3 7 months 95 ci 3 1 4 3 median overall survival os 7 4 months 95 ci 6 1 8 7 significant positive correlation ca19 9 response ttp r 0 66 p 0 01 ca19 9 response also significantly correlated os r 0 57 p 0 01 common grade 3 4 toxicities nausea vomiting 12 patients 6 8 conclusions results indicate capecitabine cisplatin regimen well tolerated moderate activity advanced btc ca19 9 response may suitable surrogate marker patients btc treated capecitabine cisplatin pubmed","probabilities":0.9799733,"Title":"Capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective single-center study","Abstract":"BACKGROUND: Palliative chemotherapy is currently the primary therapeutic approach in the treatment of advanced biliary tract cancer (BTC). Our aim was to assess the efficacy and safety of capecitabine plus cisplatin as first-line chemotherapy for patients with advanced BTC and to analyze the relationship between the level of CA19-9 and clinical outcome. METHODS: We retrospectively reviewed the records of patients who had unresectable, metastatic or recurrent BTC who were treated with capecitabine plus cisplatin. Capecitabine was administered orally at a dose of 1,000 mg/m(2) twice a day for 14 days, followed by a 1-week rest period. Cisplatin was administered intravenously on days 1 and 8 at a dose of 30 mg/m(2) for 60 min every 3 weeks. RESULTS: A total of 176 patients were enrolled. Among the 143 assessable patients, 24 (17%) had a partial response. A complete response was radiologically confirmed in 1 patient who had gallbladder cancer. Sixty-two patients (43%) had stable disease and 56 patients (39%) had progressive disease. With a median follow-up of 5.7 months, the median time-to-progression (TTP) was 3.7 months (95% CI 3.1-4.3) and the median overall survival (OS) was 7.4 months (95% CI 6.1-8.7). There was a significant positive correlation between CA19-9 response and TTP (r = 0.66, p = 0.01). CA19-9 response was also significantly correlated with OS (r = 0.57, p < 0.01). The most common grade 3/4 toxicities were nausea/vomiting [12 patients (6.8%)]. CONCLUSIONS: Our results indicate that the capecitabine/cisplatin regimen is well tolerated and has moderate activity against advanced BTC. The CA19-9 response may be a suitable surrogate marker for patients with BTC who are treated with capecitabine/cisplatin.","Source":"PubMed","category":"HUMAN","training_data":"Capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective single-center study BACKGROUND: Palliative chemotherapy is currently the primary therapeutic approach in the treatment of advanced biliary tract cancer (BTC). Our aim was to assess the efficacy and safety of capecitabine plus cisplatin as first-line chemotherapy for patients with advanced BTC and to analyze the relationship between the level of CA19-9 and clinical outcome. METHODS: We retrospectively reviewed the records of patients who had unresectable, metastatic or recurrent BTC who were treated with capecitabine plus cisplatin. Capecitabine was administered orally at a dose of 1,000 mg/m(2) twice a day for 14 days, followed by a 1-week rest period. Cisplatin was administered intravenously on days 1 and 8 at a dose of 30 mg/m(2) for 60 min every 3 weeks. RESULTS: A total of 176 patients were enrolled. Among the 143 assessable patients, 24 (17%) had a partial response. A complete response was radiologically confirmed in 1 patient who had gallbladder cancer. Sixty-two patients (43%) had stable disease and 56 patients (39%) had progressive disease. With a median follow-up of 5.7 months, the median time-to-progression (TTP) was 3.7 months (95% CI 3.1-4.3) and the median overall survival (OS) was 7.4 months (95% CI 6.1-8.7). There was a significant positive correlation between CA19-9 response and TTP (r = 0.66, p = 0.01). CA19-9 response was also significantly correlated with OS (r = 0.57, p < 0.01). The most common grade 3/4 toxicities were nausea/vomiting [12 patients (6.8%)]. CONCLUSIONS: Our results indicate that the capecitabine/cisplatin regimen is well tolerated and has moderate activity against advanced BTC. The CA19-9 response may be a suitable surrogate marker for patients with BTC who are treated with capecitabine/cisplatin. PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcome patterns care advanced biliary tract carcinoma abc experience two tertiary institutions united kingdom aims background abc 02 trial defined standard therapy patients advanced biliary tract cancer abc however outcome unselected patient population uk described aimed investigate outcome series patients abc two large uk cancer networks methods study design retrospectively reviewed cases abc presenting two uk cancer networks nine year period overall survival os factors influencing os assessed results four hundred two patients available analysis median os 6 2 months univariate analysis age 70 years p 0 047 advanced disease stage p 0 001 gall bladder primary p 0 033 poor performance status p 0 001 lack chemotherapy p 0 001 associated worse outcome survival superior 36 4 patients received palliative chemotherapy 12 5 vs 4 3 months p 0 001 multivariate analysis patients chemotherapy receive fluoropyrimidine based regimens hr 5 12 p 0 022 gemcitabine based regimens hr 5 01 p 0 021 higher mortality whereas effect platinum containing regimens borderline significance hr 2 23 p 0 086 sites age multi agent regimens significant conclusions one largest retrospective studies reporting outcome palliative chemotherapy abc confirms benefit palliative chemotherapy unselected group patients fluoropyrimidine based regimens appear effective gemcitabine based treatments pubmed","probabilities":0.9799733,"Title":"Outcome and patterns of care in advanced biliary tract carcinoma (ABC): experience from two tertiary institutions in the United Kingdom","Abstract":"AIMS AND BACKGROUND: The ABC-02 trial has defined the standard therapy for patients with advanced biliary tract cancer (ABC); however, outcome in an unselected patient population in the UK has not been described. We aimed to investigate the outcome of a series of patients with ABC from two large UK cancer networks. METHODS AND STUDY DESIGN: We retrospectively reviewed all cases of ABC presenting to two UK cancer networks over a nine-year period. Overall survival (OS) and factors influencing OS were assessed. RESULTS: Four hundred and two patients were available for analysis. The median OS was 6.2 months. On univariate analysis, age ≥70 years (P = 0.047), advanced disease stage (P <0.001), gall bladder primary (P = 0.033), poor performance status (P <0.001) and lack of chemotherapy (P <0.001) were associated with worse outcome. Survival was superior in the 36.4% of patients who received palliative chemotherapy (12.5 vs 4.3 months; P <0.001). On multivariate analysis of patients who had chemotherapy, those who did not receive fluoropyrimidine-based regimens (HR = 5.12; P = 0.022) or gemcitabine-based regimens (HR = 5.01; P = 0.021) had a higher mortality, whereas the effect of platinum-containing regimens was of borderline significance (HR = 2.23; P = 0.086). Sites, age, and multi-agent regimens were not significant. CONCLUSIONS: This is one of the largest retrospective studies reporting outcome of palliative chemotherapy for ABC. It confirms the benefit of palliative chemotherapy in an unselected group of patients. Fluoropyrimidine-based regimens appear to be as effective as gemcitabine-based treatments.","Source":"PubMed","category":"HUMAN","training_data":"Outcome and patterns of care in advanced biliary tract carcinoma (ABC): experience from two tertiary institutions in the United Kingdom AIMS AND BACKGROUND: The ABC-02 trial has defined the standard therapy for patients with advanced biliary tract cancer (ABC); however, outcome in an unselected patient population in the UK has not been described. We aimed to investigate the outcome of a series of patients with ABC from two large UK cancer networks. METHODS AND STUDY DESIGN: We retrospectively reviewed all cases of ABC presenting to two UK cancer networks over a nine-year period. Overall survival (OS) and factors influencing OS were assessed. RESULTS: Four hundred and two patients were available for analysis. The median OS was 6.2 months. On univariate analysis, age ≥70 years (P = 0.047), advanced disease stage (P <0.001), gall bladder primary (P = 0.033), poor performance status (P <0.001) and lack of chemotherapy (P <0.001) were associated with worse outcome. Survival was superior in the 36.4% of patients who received palliative chemotherapy (12.5 vs 4.3 months; P <0.001). On multivariate analysis of patients who had chemotherapy, those who did not receive fluoropyrimidine-based regimens (HR = 5.12; P = 0.022) or gemcitabine-based regimens (HR = 5.01; P = 0.021) had a higher mortality, whereas the effect of platinum-containing regimens was of borderline significance (HR = 2.23; P = 0.086). Sites, age, and multi-agent regimens were not significant. CONCLUSIONS: This is one of the largest retrospective studies reporting outcome of palliative chemotherapy for ABC. It confirms the benefit of palliative chemotherapy in an unselected group of patients. Fluoropyrimidine-based regimens appear to be as effective as gemcitabine-based treatments. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative risk score predict occult metastatic locally advanced disease patients resectable perihilar cholangiocarcinoma imaging background many patients resectable perihilar cholangiocarcinoma phc imaging diagnosed intraoperatively occult metastatic locally advanced disease precluding curative intent resection study aimed develop validate preoperative risk score study design patients resectable phc imaging underwent operations 2 high volume centers us europe 2000 2015 included multivariable logistic regression analysis used develop risk score cross validation used validate score alternating 2 centers training testing datasets results 566 patients underwent operations 309 55 patients resection 257 45 patients curative intent resection precluded due distant metastasis n 151 27 locally advanced disease n 106 19 preoperative predictors included bilirubin 2 mg dl bile duct involvement imaging portal vein involvement imaging 180 degrees hepatic artery involvement imaging 180 degrees suspicious lymph nodes imaging new risk score c index 0 75 cross validation provided significantly accurate predictions bismuth classification c index 0 62 blumgart staging c index 0 67 ctnm staging c index 0 68 new risk score identified 4 risk groups occult metastatic locally advanced disease low 14 7 intermediate 29 5 high 47 3 high risk 81 3 preoperative score groups also predicted survival operation irrespective intraoperative findings p 0 001 conclusions validated risk score predict occult distant metastatic locally advanced phc based 5 preoperatively available factors score useful preoperative shared decision making selection patients neoadjuvant clinical trials pubmed","probabilities":0.9799733,"Title":"Preoperative Risk Score to Predict Occult Metastatic or Locally Advanced Disease in Patients with Resectable Perihilar Cholangiocarcinoma on Imaging","Abstract":"BACKGROUND: Many patients with resectable perihilar cholangiocarcinoma (PHC) on imaging are diagnosed intraoperatively with occult metastatic or locally advanced disease, precluding a curative-intent resection. This study aimed to develop and validate a preoperative risk score. STUDY DESIGN: Patients with resectable PHC on imaging who underwent operations in 2 high-volume centers (US and Europe) between 2000 and 2015 were included. Multivariable logistic regression analysis was used to develop the risk score. Cross-validation was used to validate the score, alternating the 2 centers as \"training\" and \"testing\" datasets. RESULTS: Of 566 patients who underwent operations, 309 (55%) patients had a resection, and in 257 (45%) patients, a curative-intent resection was precluded due to distant metastasis (n = 151 [27%]) or locally advanced disease (n = 106 [19%]). Preoperative predictors included bilirubin >2 mg/dL, bile duct involvement on imaging, portal vein involvement on imaging (≥180 degrees), hepatic artery involvement on imaging (≥180 degrees), and suspicious lymph nodes on imaging. The new risk score (c-index 0.75 after cross-validation) provided significantly more accurate predictions than the Bismuth classification (c-index 0.62), Blumgart T-staging (c-index 0.67), and cTNM staging (c-index 0.68). The new risk score identified 4 risk groups for occult metastatic or locally advanced disease: low (14.7%), intermediate (29.5%), high (47.3%), and very high risk (81.3%). The preoperative score groups also predicted survival after operation, irrespective of intraoperative findings (p < 0.001). CONCLUSIONS: The validated risk score can predict occult distant metastatic or locally advanced PHC based on 5 preoperatively available factors. The score can be useful in preoperative shared decision making and selection of patients in neoadjuvant clinical trials.","Source":"PubMed","category":"HUMAN","training_data":"Preoperative Risk Score to Predict Occult Metastatic or Locally Advanced Disease in Patients with Resectable Perihilar Cholangiocarcinoma on Imaging BACKGROUND: Many patients with resectable perihilar cholangiocarcinoma (PHC) on imaging are diagnosed intraoperatively with occult metastatic or locally advanced disease, precluding a curative-intent resection. This study aimed to develop and validate a preoperative risk score. STUDY DESIGN: Patients with resectable PHC on imaging who underwent operations in 2 high-volume centers (US and Europe) between 2000 and 2015 were included. Multivariable logistic regression analysis was used to develop the risk score. Cross-validation was used to validate the score, alternating the 2 centers as \"training\" and \"testing\" datasets. RESULTS: Of 566 patients who underwent operations, 309 (55%) patients had a resection, and in 257 (45%) patients, a curative-intent resection was precluded due to distant metastasis (n = 151 [27%]) or locally advanced disease (n = 106 [19%]). Preoperative predictors included bilirubin >2 mg/dL, bile duct involvement on imaging, portal vein involvement on imaging (≥180 degrees), hepatic artery involvement on imaging (≥180 degrees), and suspicious lymph nodes on imaging. The new risk score (c-index 0.75 after cross-validation) provided significantly more accurate predictions than the Bismuth classification (c-index 0.62), Blumgart T-staging (c-index 0.67), and cTNM staging (c-index 0.68). The new risk score identified 4 risk groups for occult metastatic or locally advanced disease: low (14.7%), intermediate (29.5%), high (47.3%), and very high risk (81.3%). The preoperative score groups also predicted survival after operation, irrespective of intraoperative findings (p < 0.001). CONCLUSIONS: The validated risk score can predict occult distant metastatic or locally advanced PHC based on 5 preoperatively available factors. The score can be useful in preoperative shared decision making and selection of patients in neoadjuvant clinical trials. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact tumor growth type 7th ajcc staging system intrahepatic cholangiocarcinoma single center experience 659 cases objective noticeable changes made 7th american joint committee cancer ajcc tumor node metastasis tnm staging intrahepatic cholangiocarcinoma ihcc validated prognostic impact tumor staging macroscopic curative resection ihcc methods cohort 659 ihcc patients underwent r0 n 539 r1 n 120 resection selected exclusion r2 resection n 111 study patients followed 24 months death patient lost survival analysis results anatomical resection performed 599 90 9 concurrent bile duct resection conducted 97 14 7 median survival periods following r0 r1 r2 resections 28 12 3 months respectively p 0 000 r0 resection group 1 3 5 10 year tumor recurrence rates 36 4 57 9 64 7 65 0 respectively 1 3 5 10 year patient survival rates 73 1 44 2 33 0 23 1 respectively independent risk factors tumor recurrence patient survival tumor growth type tumor size 5 cm perineural invasion lymph node metastasis according 7th ajcc staging system prognostic contrast marginal stage t2 4 tumors without lymph node metastasis p 0 8 redefined staging system tumor growth types risk factors including tumor number perineural lymphovascular invasion clear prognostic contrast achieved among t1 3 stages p 0 000 conclusion growth type ihcc seems essential determining tumor stage although stratification 7th ajcc ihcc staging system seems reasonably established refinements validation improve prognostic predictability pubmed","probabilities":0.9799733,"Title":"Prognostic Impact of Tumor Growth Type on 7th AJCC Staging System for Intrahepatic Cholangiocarcinoma: a Single-Center Experience of 659 Cases","Abstract":"OBJECTIVE: Because noticeable changes were made to the 7th American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging for intrahepatic cholangiocarcinoma (IHCC), we validated the prognostic impact of tumor staging after macroscopic curative resection of IHCC. METHODS: A cohort of 659 IHCC patients who underwent R0 (n = 539) or R1 (n = 120) resection were selected with exclusion of R2 resection (n = 111). Study patients were followed up for ≥24 months or until death with no patient lost during survival analysis. RESULTS: Anatomical resection was performed in 599 (90.9%) and concurrent bile duct resection was conducted in 97 (14.7%). Median survival periods following R0, R1, and R2 resections were 28, 12, and 3 months, respectively (p = 0.000). In the R0 resection group, the 1-, 3-, 5-, and 10-year tumor recurrence rates were 36.4%, 57.9%, 64.7%, and 65.0%, respectively, and the 1-, 3-, 5-, and 10-year patient survival rates were 73.1%, 44.2%, 33.0%, and 23.1%, respectively. Independent risk factors for tumor recurrence and patient survival were tumor growth type, tumor size > 5 cm, perineural invasion, and lymph node metastasis. According to the 7th AJCC staging system, the prognostic contrast was marginal in stage T2-4 tumors without lymph node metastasis (p > 0.8). With our redefined staging system with tumor growth types and risk factors including tumor number and perineural/lymphovascular invasion, clear prognostic contrast was achieved among T1-3 stages (p = 0.000). CONCLUSION: Growth type of IHCC seems to be essential for determining tumor stage. Although the stratification of the 7th AJCC IHCC staging system seems reasonably established, refinements and further validation could improve prognostic predictability.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Impact of Tumor Growth Type on 7th AJCC Staging System for Intrahepatic Cholangiocarcinoma: a Single-Center Experience of 659 Cases OBJECTIVE: Because noticeable changes were made to the 7th American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging for intrahepatic cholangiocarcinoma (IHCC), we validated the prognostic impact of tumor staging after macroscopic curative resection of IHCC. METHODS: A cohort of 659 IHCC patients who underwent R0 (n = 539) or R1 (n = 120) resection were selected with exclusion of R2 resection (n = 111). Study patients were followed up for ≥24 months or until death with no patient lost during survival analysis. RESULTS: Anatomical resection was performed in 599 (90.9%) and concurrent bile duct resection was conducted in 97 (14.7%). Median survival periods following R0, R1, and R2 resections were 28, 12, and 3 months, respectively (p = 0.000). In the R0 resection group, the 1-, 3-, 5-, and 10-year tumor recurrence rates were 36.4%, 57.9%, 64.7%, and 65.0%, respectively, and the 1-, 3-, 5-, and 10-year patient survival rates were 73.1%, 44.2%, 33.0%, and 23.1%, respectively. Independent risk factors for tumor recurrence and patient survival were tumor growth type, tumor size > 5 cm, perineural invasion, and lymph node metastasis. According to the 7th AJCC staging system, the prognostic contrast was marginal in stage T2-4 tumors without lymph node metastasis (p > 0.8). With our redefined staging system with tumor growth types and risk factors including tumor number and perineural/lymphovascular invasion, clear prognostic contrast was achieved among T1-3 stages (p = 0.000). CONCLUSION: Growth type of IHCC seems to be essential for determining tumor stage. Although the stratification of the 7th AJCC IHCC staging system seems reasonably established, refinements and further validation could improve prognostic predictability. PubMed","prediction_labels":"HUMAN"},{"cleaned":"total meso pancreatoduodenum excision pancreaticoduodenectomy lower biliary tract cancer background incomplete tumor resection insufficient lymphadenectomy following pancreaticoduodenectomy pd lower biliary tract cancer results dismal outcome study aimed compare short term outcomes pd total meso pancreatoduodenum excision tmpde conventional procedure lower biliary tract cancer methods patients underwent pd lower biliary tract cancer may 2003 march 2015 included study devised new surgical technique tmpde mesenteric plane surgery artery first approach achieving complete clearance peripancreatic retroperitoneal tissue lymph nodes perioperative data including complications short term survival evaluated results total 74 consecutive patients underwent pd 41 patients underwent conventional pd cpd 33 underwent tmpde tumor stages similar two study groups r0 achieved 32 patients 78 0 cpd 31 patients 93 9 tmpde p 0 046 survival rates 1 3 years surgery 82 5 64 0 cpd group median follow period 44 6 months 92 8 84 4 tmpde group median follow period 28 6 months respectively conclusions tmpde technique significantly increased r0 resection contributed better oncological outcomes lower biliary tract cancer pubmed","probabilities":0.7966102,"Title":"Total meso-pancreatoduodenum excision with pancreaticoduodenectomy in lower biliary tract cancer","Abstract":"BACKGROUND: Incomplete tumor resection with insufficient lymphadenectomy following a pancreaticoduodenectomy (PD) for lower biliary tract cancer results in a dismal outcome. This study aimed to compare the short-term outcomes of PD between total meso-pancreatoduodenum excision (tMPDe) and the conventional procedure for lower biliary tract cancer. METHODS: Patients who underwent PD for lower biliary tract cancer between May 2003 and March 2015 were included in this study. We have devised a new surgical technique, tMPDe, as a mesenteric plane surgery with an artery-first approach, for achieving complete clearance of the peripancreatic retroperitoneal tissue and lymph nodes. Perioperative data, including complications and short-term survival, were evaluated. RESULTS: A total of 74 consecutive patients underwent a PD: 41 patients underwent conventional PD (cPD), and 33 underwent tMPDe. The tumor stages were similar in the two study groups. R0 was achieved in 32 patients (78.0 %) with cPD and in 31 patients (93.9 %) with tMPDe (p = 0.046). The survival rates at 1 and 3 years after surgery were 82.5 and 64.0 % for the cPD group, with a median follow-up period of 44.6 months, and 92.8 and 84.4 % for the tMPDe group, with a median follow-up period of 28.6 months, respectively. CONCLUSIONS: The tMPDe technique significantly increased R0 resection and contributed to better oncological outcomes in lower biliary tract cancer.","Source":"PubMed","category":"HUMAN","training_data":"Total meso-pancreatoduodenum excision with pancreaticoduodenectomy in lower biliary tract cancer BACKGROUND: Incomplete tumor resection with insufficient lymphadenectomy following a pancreaticoduodenectomy (PD) for lower biliary tract cancer results in a dismal outcome. This study aimed to compare the short-term outcomes of PD between total meso-pancreatoduodenum excision (tMPDe) and the conventional procedure for lower biliary tract cancer. METHODS: Patients who underwent PD for lower biliary tract cancer between May 2003 and March 2015 were included in this study. We have devised a new surgical technique, tMPDe, as a mesenteric plane surgery with an artery-first approach, for achieving complete clearance of the peripancreatic retroperitoneal tissue and lymph nodes. Perioperative data, including complications and short-term survival, were evaluated. RESULTS: A total of 74 consecutive patients underwent a PD: 41 patients underwent conventional PD (cPD), and 33 underwent tMPDe. The tumor stages were similar in the two study groups. R0 was achieved in 32 patients (78.0 %) with cPD and in 31 patients (93.9 %) with tMPDe (p = 0.046). The survival rates at 1 and 3 years after surgery were 82.5 and 64.0 % for the cPD group, with a median follow-up period of 44.6 months, and 92.8 and 84.4 % for the tMPDe group, with a median follow-up period of 28.6 months, respectively. CONCLUSIONS: The tMPDe technique significantly increased R0 resection and contributed to better oncological outcomes in lower biliary tract cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma prognostic factors liver resection liver resection may represent hope cure patients intrahepatic cholangiocarcinoma ihc long term results still far satisfactory impact prognostic factors still controversial fifty five patients underwent hepatectomy ihc 1997 2008 unit features patients tumors operations postoperative long term results retrospectively assessed twenty one patients hbv hcv infection four congenital biliary dilatation thirty two patients increased ca 19 9 12 multiple 4 tumors operations included 43 major resections 9 resections biliary confluence 40 regional lymphadenectomies operative mortality morbidity 0 27 3 respectively 44 r0 resections 80 0 lymphadenectomy yielded lymph node metastases 14 cases 14 40 35 0 five year overall disease free survival rates 30 2 27 5 respectively multivariate analysis strongest poor prognostic factor overall survival tumor stage factor multiplicity lesions 4 tumor grading 2 significant predictor recurrence ca19 9 100 iu ml tumor grading 2 found significantly related early multinodular hepatic recurrence patients lymph node metastases significantly lower overall disease free survival patients underwent lymph node dissection negative lymph nodes final pathology showed significantly higher 5 year disease free survival patients underwent lymphadenectomy conclusion results support role hepatectomy regional lymphadenectomy best available treatment ihc prognosis liver resection correlates clinical stage multiplicity lesions pubmed","probabilities":0.9799733,"Title":"Intrahepatic cholangiocarcinoma: prognostic factors after liver resection","Abstract":"Liver resection may represent the only hope of cure for patients with intrahepatic cholangiocarcinoma (IHC) but long-term results are still far from satisfactory and the impact of prognostic factors is still controversial. Fifty-five patients underwent hepatectomy for IHC between 1997 and 2008 in our unit. Features of the patients and the tumors, operations, postoperative and long-term results were retrospectively assessed. Twenty-one patients had HBV/HCV infection, four had congenital biliary dilatation. Thirty-two patients had increased CA 19-9; 12 had multiple (≥ 4) tumors. Operations included 43 major resections, with 9 resections of biliary confluence, 40 regional lymphadenectomies. Operative mortality and morbidity were 0 and 27.3%, respectively. There were 44 R0-resections (80.0%). Lymphadenectomy yielded lymph node metastases in 14 cases (14/40; 35.0%). Five-year overall and disease-free survival rates were 30.2 and 27.5%, respectively. At multivariate analysis the strongest poor prognostic factor for overall survival was tumor stage. This factor, with multiplicity of lesions (≥ 4) and tumor grading > 2, was significant predictor of recurrence. CA19-9 > 100 IU/mL and tumor grading > 2 were found to be significantly related with early multinodular hepatic recurrence. Patients with lymph node metastases had significantly lower overall and disease-free survival but patients who underwent lymph node dissection with negative lymph nodes at final pathology showed significantly higher 5-year disease-free survival than patients who did not underwent lymphadenectomy. In conclusion, these results support the role of hepatectomy with regional lymphadenectomy as the best available treatment for IHC. Prognosis after liver resection correlates with clinical stage and multiplicity of lesions.","Source":"PubMed","category":"HUMAN","training_data":"Intrahepatic cholangiocarcinoma: prognostic factors after liver resection Liver resection may represent the only hope of cure for patients with intrahepatic cholangiocarcinoma (IHC) but long-term results are still far from satisfactory and the impact of prognostic factors is still controversial. Fifty-five patients underwent hepatectomy for IHC between 1997 and 2008 in our unit. Features of the patients and the tumors, operations, postoperative and long-term results were retrospectively assessed. Twenty-one patients had HBV/HCV infection, four had congenital biliary dilatation. Thirty-two patients had increased CA 19-9; 12 had multiple (≥ 4) tumors. Operations included 43 major resections, with 9 resections of biliary confluence, 40 regional lymphadenectomies. Operative mortality and morbidity were 0 and 27.3%, respectively. There were 44 R0-resections (80.0%). Lymphadenectomy yielded lymph node metastases in 14 cases (14/40; 35.0%). Five-year overall and disease-free survival rates were 30.2 and 27.5%, respectively. At multivariate analysis the strongest poor prognostic factor for overall survival was tumor stage. This factor, with multiplicity of lesions (≥ 4) and tumor grading > 2, was significant predictor of recurrence. CA19-9 > 100 IU/mL and tumor grading > 2 were found to be significantly related with early multinodular hepatic recurrence. Patients with lymph node metastases had significantly lower overall and disease-free survival but patients who underwent lymph node dissection with negative lymph nodes at final pathology showed significantly higher 5-year disease-free survival than patients who did not underwent lymphadenectomy. In conclusion, these results support the role of hepatectomy with regional lymphadenectomy as the best available treatment for IHC. Prognosis after liver resection correlates with clinical stage and multiplicity of lesions. PubMed","prediction_labels":"HUMAN"},{"cleaned":"bile duct involvement portends poor prognosis resected gallbladder carcinoma background gallbladder cancer gbc carries unfavorable prognosis high mortality retrospective study conducted identify prognostic factors resection gbc assist selecting appropriate surgical adjuvant therapy methods sixty two patients two institutions identified gbc pathology 25 cancer unresectable presentation remaining 37 patients comprised study population log rank analysis used assess univariate association disease free survival dfs disease specific survival dss cox regression used multivariate analysis results median dfs dss 22 6 28 5 months respectively median follow 44 2 months univariate analysis bile duct bd involvement significantly associated decreased dfs p 001 dss p 004 bd involvement uniformly fatal ln involvement significantly associated dfs dss p 85 p 54 conclusions patients bd involvement population died disease subset patients resectable gbc bd involvement group high risk recurrence treated small population preoperative intraoperative methods evaluating bd involvement unreliable stn","probabilities":0.9799733,"Title":"Bile Duct Involvement Portends Poor Prognosis In Resected Gallbladder Carcinoma","Abstract":"Background: Gallbladder cancer (GBC) carries an unfavorable prognosis with high mortality. This retrospective study was conducted to identify prognostic factors after resection of GBC, to assist in selecting appropriate surgical and adjuvant therapy. \r\n\r\n Methods: Sixty-two patients from two institutions were identified with GBC by pathology. In 25, the cancer was unresectable at presentation. The remaining 37 patients comprised the study population. Log-rank analysis was used to assess univariate association with disease-free survival (DFS) and disease-specific survival (DSS). Cox regression was used for multivariate analysis. \r\n\r\n Results: Median DFS and DSS were 22.6 and 28.5 months respectively, with a median follow-up of 44.2 months. On univariate analysis, bile duct (BD) involvement was significantly associated with decreased DFS (P ≤ .001) and DSS (P = .004). BD involvement was uniformly fatal. LN involvement was not significantly associated with DFS or DSS (P = .85, P = .54). \r\n\r\n Conclusions: All patients with BD involvement in our population died of the disease. The subset of patients with resectable GBC and BD involvement is a group that is at high risk for recurrence and should be treated as such. In our small population, preoperative and intraoperative methods evaluating BD involvement were unreliable.","Source":"STN","category":"HUMAN","training_data":"Bile Duct Involvement Portends Poor Prognosis In Resected Gallbladder Carcinoma Background: Gallbladder cancer (GBC) carries an unfavorable prognosis with high mortality. This retrospective study was conducted to identify prognostic factors after resection of GBC, to assist in selecting appropriate surgical and adjuvant therapy. \r\n\r\n Methods: Sixty-two patients from two institutions were identified with GBC by pathology. In 25, the cancer was unresectable at presentation. The remaining 37 patients comprised the study population. Log-rank analysis was used to assess univariate association with disease-free survival (DFS) and disease-specific survival (DSS). Cox regression was used for multivariate analysis. \r\n\r\n Results: Median DFS and DSS were 22.6 and 28.5 months respectively, with a median follow-up of 44.2 months. On univariate analysis, bile duct (BD) involvement was significantly associated with decreased DFS (P ≤ .001) and DSS (P = .004). BD involvement was uniformly fatal. LN involvement was not significantly associated with DFS or DSS (P = .85, P = .54). \r\n\r\n Conclusions: All patients with BD involvement in our population died of the disease. The subset of patients with resectable GBC and BD involvement is a group that is at high risk for recurrence and should be treated as such. In our small population, preoperative and intraoperative methods evaluating BD involvement were unreliable. STN","prediction_labels":"HUMAN"},{"cleaned":"high cd47 expression correlates shorter survival lymph node metastasis cholangiocarcinoma subgroup abstract available google scholar","probabilities":0.9799733,"Title":"High Cd47 Expression Correlates With A Shorter Survival And Lymph Node Metastasis Of Cholangiocarcinoma Subgroup","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"High Cd47 Expression Correlates With A Shorter Survival And Lymph Node Metastasis Of Cholangiocarcinoma Subgroup Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"body size indicators risk gallbladder cancer pooled analysis individual level data 19 prospective cohort studies background established risk factors gallbladder cancer beyond gallstones recent studies suggest higher risk high body mass index bmi indicator general heaviness evidence body size measures lacking methods associations adult bmi young adult bmi height adult weight gain waist circumference wc waist height ratio whtr hip circumference hc waist hip ratio whr gallbladder cancer risk evaluated individual level data 1 878 801 participants 19 prospective cohort studies 14 studies circumference measures harmonized included analysis multivariable cox proportional hazards regression estimated hazard ratios hr 95 confidence intervals ci results enrollment 567 gallbladder cancer cases identified 20 1 million person years observation including 361 cases wc measures higher adult bmi per 5 kg m 2 hr 1 24 95 ci 1 13 1 35 young adult bmi per 5 kg m 2 hr 1 12 95 ci 1 00 1 26 adult weight gain per 5 kg hr 1 07 95 ci 1 02 1 12 height per 5 cm hr 1 10 95 ci 1 03 1 17 wc per 5 cm hr 1 09 95 ci 1 02 1 17 whtr per 0 1 unit hr 1 24 95 ci 1 00 1 54 hc per 5 cm hr 1 13 95 ci 1 04 1 22 whr per 0 1 unit hr 1 03 95 ci 0 87 1 22 associated higher risks gallbladder cancer results differ meaningfully sex demographic lifestyle factors conclusions findings indicate measures overall central excess body weight associated higher gallbladder cancer risks impact excess body weight important potentially preventable gallbladder cancer risk factor cancer epidemiol biomarkers prev 26 4 597 606 2017 aacr pubmed","probabilities":0.9799733,"Title":"Body Size Indicators and Risk of Gallbladder Cancer: Pooled Analysis of Individual-Level Data from 19 Prospective Cohort Studies","Abstract":"Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking.Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist-height ratio (WHtR), hip circumference (HC), and waist-hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI).Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m(2), HR: 1.24; 95% CI, 1.13-1.35), young adult BMI (per 5 kg/m(2), HR: 1.12; 95% CI, 1.00-1.26), adult weight gain (per 5 kg, HR: 1.07; 95% CI, 1.02-1.12), height (per 5 cm, HR: 1.10; 95% CI, 1.03-1.17), WC (per 5 cm, HR: 1.09; 95% CI, 1.02-1.17), WHtR (per 0.1 unit, HR: 1.24; 95% CI, 1.00-1.54), and HC (per 5 cm, HR: 1.13; 95% CI, 1.04-1.22), but not WHR (per 0.1 unit, HR: 1.03; 95% CI, 0.87-1.22), were associated with higher risks of gallbladder cancer, and results did not differ meaningfully by sex or other demographic/lifestyle factors.Conclusions: These findings indicate that measures of overall and central excess body weight are associated with higher gallbladder cancer risks.Impact: Excess body weight is an important, and potentially preventable, gallbladder cancer risk factor. Cancer Epidemiol Biomarkers Prev; 26(4); 597-606. ©2017 AACR.","Source":"PubMed","category":"HUMAN","training_data":"Body Size Indicators and Risk of Gallbladder Cancer: Pooled Analysis of Individual-Level Data from 19 Prospective Cohort Studies Background: There are few established risk factors for gallbladder cancer beyond gallstones. Recent studies suggest a higher risk with high body mass index (BMI), an indicator of general heaviness, but evidence from other body size measures is lacking.Methods: Associations of adult BMI, young adult BMI, height, adult weight gain, waist circumference (WC), waist-height ratio (WHtR), hip circumference (HC), and waist-hip ratio (WHR) with gallbladder cancer risk were evaluated. Individual-level data from 1,878,801 participants in 19 prospective cohort studies (14 studies had circumference measures) were harmonized and included in this analysis. Multivariable Cox proportional hazards regression estimated hazard ratios (HR) and 95% confidence intervals (CI).Results: After enrollment, 567 gallbladder cancer cases were identified during 20.1 million person-years of observation, including 361 cases with WC measures. Higher adult BMI (per 5 kg/m(2), HR: 1.24; 95% CI, 1.13-1.35), young adult BMI (per 5 kg/m(2), HR: 1.12; 95% CI, 1.00-1.26), adult weight gain (per 5 kg, HR: 1.07; 95% CI, 1.02-1.12), height (per 5 cm, HR: 1.10; 95% CI, 1.03-1.17), WC (per 5 cm, HR: 1.09; 95% CI, 1.02-1.17), WHtR (per 0.1 unit, HR: 1.24; 95% CI, 1.00-1.54), and HC (per 5 cm, HR: 1.13; 95% CI, 1.04-1.22), but not WHR (per 0.1 unit, HR: 1.03; 95% CI, 0.87-1.22), were associated with higher risks of gallbladder cancer, and results did not differ meaningfully by sex or other demographic/lifestyle factors.Conclusions: These findings indicate that measures of overall and central excess body weight are associated with higher gallbladder cancer risks.Impact: Excess body weight is an important, and potentially preventable, gallbladder cancer risk factor. Cancer Epidemiol Biomarkers Prev; 26(4); 597-606. ©2017 AACR. PubMed","prediction_labels":"HUMAN"},{"cleaned":"carcinoma ampulla vater morphological immunophenotypical classification predicts overall survival objectives objective study verify histopathological differentiation ampullary carcinoma surgical resection may related survival methods prognostic role accurate histological immunohistochemical classification investigated multicentric series carcinoma ampulla vater immunohistochemical expression cytokeratin 7 ck7 ck20 analyzed different morphological histotypes ampullary cancers results compared overall survival results 72 ampullary cancers 48 6 classified pancreaticobiliary type carcinomas 43 1 classified intestinal type carcinomas 8 3 classified unusual type carcinomas cytokeratin 20 expressed 28 90 3 31 intestinal type carcinomas whereas always negative pancreaticobiliary histotype ck7 expressed 32 91 4 35 pancreaticobiliary type carcinomas 18 58 1 31 intestinal type carcinomas univariate analysis overall survival influenced significantly pathological factor lymph node involvement histological immunohistochemical subtyping furthermore using multivariate cox regression model lymph node metastasis ck20 identified significant independent factors related prognosis conclusion results prove clinical use ampullary cancer subclassification based different histotypes indicate useful role ck7 ck20 expression profile consistent histopathological classification prognostic relevance pubmed","probabilities":0.9799733,"Title":"Carcinoma of the ampulla of Vater: morphological and immunophenotypical classification predicts overall survival","Abstract":"OBJECTIVES: The objective of the study was to verify if histopathological differentiation of ampullary carcinoma after surgical resection may be related to survival. METHODS: The prognostic role of an accurate histological and immunohistochemical classification has been investigated in a multicentric series of carcinoma of the ampulla of Vater. Immunohistochemical expression of cytokeratin 7 (CK7) and CK20 were analyzed in the different morphological histotypes of ampullary cancers, and results were compared with overall survival. RESULTS: Of 72 ampullary cancers, 48.6% were classified as pancreaticobiliary-type carcinomas, 43.1% were classified as intestinal-type carcinomas, and 8.3% were classified as \"unusual\"-type carcinomas. Cytokeratin 20 was expressed in 28 (90.3%) of the 31 intestinal-type carcinomas, whereas it was always negative in the pancreaticobiliary histotype; CK7 was expressed in 32 (91.4%) of the 35 pancreaticobiliary-type carcinomas and in 18 (58.1%) of the 31 intestinal-type carcinomas. By univariate analysis, overall survival was influenced significantly by pathological T factor, lymph node involvement, and histological/immunohistochemical subtyping. Furthermore, using a multivariate Cox regression model, lymph node metastasis and CK20 were identified as significant independent factors related to prognosis. CONCLUSION: Our results prove the clinical use of ampullary cancer subclassification based on different histotypes and indicate the useful role of the CK7/CK20 expression profile for consistent histopathological classification and prognostic relevance.","Source":"PubMed","category":"HUMAN","training_data":"Carcinoma of the ampulla of Vater: morphological and immunophenotypical classification predicts overall survival OBJECTIVES: The objective of the study was to verify if histopathological differentiation of ampullary carcinoma after surgical resection may be related to survival. METHODS: The prognostic role of an accurate histological and immunohistochemical classification has been investigated in a multicentric series of carcinoma of the ampulla of Vater. Immunohistochemical expression of cytokeratin 7 (CK7) and CK20 were analyzed in the different morphological histotypes of ampullary cancers, and results were compared with overall survival. RESULTS: Of 72 ampullary cancers, 48.6% were classified as pancreaticobiliary-type carcinomas, 43.1% were classified as intestinal-type carcinomas, and 8.3% were classified as \"unusual\"-type carcinomas. Cytokeratin 20 was expressed in 28 (90.3%) of the 31 intestinal-type carcinomas, whereas it was always negative in the pancreaticobiliary histotype; CK7 was expressed in 32 (91.4%) of the 35 pancreaticobiliary-type carcinomas and in 18 (58.1%) of the 31 intestinal-type carcinomas. By univariate analysis, overall survival was influenced significantly by pathological T factor, lymph node involvement, and histological/immunohistochemical subtyping. Furthermore, using a multivariate Cox regression model, lymph node metastasis and CK20 were identified as significant independent factors related to prognosis. CONCLUSION: Our results prove the clinical use of ampullary cancer subclassification based on different histotypes and indicate the useful role of the CK7/CK20 expression profile for consistent histopathological classification and prognostic relevance. PubMed","prediction_labels":"HUMAN"},{"cleaned":"predictive performance blumgart staging perihilar cholangiocarcinoma japanese center background blumgart system used local tumor assessment perihilar cholangiocarcinoma predict resectability survival t3 tumors considered unresectable disease aim validate predictive performance system using japanese cohort methods medical records consecutive patients perihilar cholangiocarcinoma 2006 2016 retrospectively reviewed resectability surgical procedure r0 resection rate survival compared among stages results among 729 study patients 191 patients t1 tumors 94 patients t2 tumors 444 60 9 patients t3 tumors according blumgart stage resection performed 513 70 4 patients resectability rate decreased progression stage 89 0 t1 79 8 t2 60 4 t3 tumors p 0 001 incidences left hepatic trisectionectomy portal vein resection 44 0 54 1 respectively patients t3 tumors significantly greater t1 2 tumors p 0 001 p 0 001 r0 resection reduced advanced stage 92 4 t1 81 3 t2 70 9 t3 tumors p 0 001 5 year survival rate 53 4 38 4 19 7 t1 t2 t3 tumors respectively p 0 001 59 6 48 6 30 7 respectively resected cohort p 0 001 conclusion blumgart stage closely associated resectability rate surgical procedures r0 resection rate survival time suggesting stage works well presurgical staging system however unresectable classification t3 tumors revised stn","probabilities":0.9799733,"Title":"Predictive Performance Of Blumgart T Staging For Perihilar Cholangiocarcinoma In A Japanese Center","Abstract":"Background: The Blumgart system has been used for local tumor assessment in perihilar cholangiocarcinoma to predict resectability and survival, and T3 tumors are considered unresectable disease. The aim was to validate the predictive performance of this system using a Japanese cohort. \r\n\r\n Methods: Medical records of consecutive patients with perihilar cholangiocarcinoma between 2006 and 2016 were retrospectively reviewed. Resectability, surgical procedure, R0 resection rate, and survival were compared among T stages. \r\n\r\n Results: Among 729 study patients, 191 patients had T1 tumors, 94 patients had T2 tumors, and 444 (60.9%) patients had T3 tumors according to the Blumgart T stage. Resection was performed in 513 (70.4%) patients; resectability rate decreased with the progression of T stage: 89.0% in T1, 79.8% in T2, and 60.4% in T3 tumors (P < 0.001). The incidences of left hepatic trisectionectomy and portal vein resection were 44.0% and 54.1%, respectively, in patients with T3 tumors, which were significantly greater than those of T1/2 tumors (P = 0.001 and P < 0.001). R0 resection reduced with advanced T stage: 92.4% in T1, 81.3% in T2, and 70.9% in T3 tumors (P < 0.001). The 5-year survival rate was 53.4%, 38.4%, and 19.7% in T1, T2, and T3 tumors, respectively (P < 0.001); that was 59.6%, 48.6%, and 30.7%, respectively, in the resected cohort (P < 0.001). \r\n\r\n Conclusion: Blumgart T stage was closely associated with the resectability rate, surgical procedures, R0 resection rate, and survival time, suggesting that the T stage works as well as a presurgical staging system. However, the unresectable classification of T3 tumors should be revised.","Source":"STN","category":"HUMAN","training_data":"Predictive Performance Of Blumgart T Staging For Perihilar Cholangiocarcinoma In A Japanese Center Background: The Blumgart system has been used for local tumor assessment in perihilar cholangiocarcinoma to predict resectability and survival, and T3 tumors are considered unresectable disease. The aim was to validate the predictive performance of this system using a Japanese cohort. \r\n\r\n Methods: Medical records of consecutive patients with perihilar cholangiocarcinoma between 2006 and 2016 were retrospectively reviewed. Resectability, surgical procedure, R0 resection rate, and survival were compared among T stages. \r\n\r\n Results: Among 729 study patients, 191 patients had T1 tumors, 94 patients had T2 tumors, and 444 (60.9%) patients had T3 tumors according to the Blumgart T stage. Resection was performed in 513 (70.4%) patients; resectability rate decreased with the progression of T stage: 89.0% in T1, 79.8% in T2, and 60.4% in T3 tumors (P < 0.001). The incidences of left hepatic trisectionectomy and portal vein resection were 44.0% and 54.1%, respectively, in patients with T3 tumors, which were significantly greater than those of T1/2 tumors (P = 0.001 and P < 0.001). R0 resection reduced with advanced T stage: 92.4% in T1, 81.3% in T2, and 70.9% in T3 tumors (P < 0.001). The 5-year survival rate was 53.4%, 38.4%, and 19.7% in T1, T2, and T3 tumors, respectively (P < 0.001); that was 59.6%, 48.6%, and 30.7%, respectively, in the resected cohort (P < 0.001). \r\n\r\n Conclusion: Blumgart T stage was closely associated with the resectability rate, surgical procedures, R0 resection rate, and survival time, suggesting that the T stage works as well as a presurgical staging system. However, the unresectable classification of T3 tumors should be revised. STN","prediction_labels":"HUMAN"},{"cleaned":"us characteristics prediction neoplasm gallbladder polyps 10 mm larger purpose evaluate characteristics gallbladder polyps 10 mm larger predict neoplasm us examinations materials methods fifty three patients gallbladder polyps 10 mm follow images pathologic diagnosis included retrospective study images reports reviewed determine imaging characteristics gallbladder polyps univariate multivariate analyses used evaluate predictors neoplastic polyp results neoplastic polyp verified 12 53 patients mean size 13 9 mm univariate analysis revealed adjacent gallbladder wall thickening larger size 15 mm older age 57 years absence hyperechoic foci polyp ct visibility sessile shape solitary polyp irregular surface significant predictors neoplastic polyp multivariate analysis larger size 15 mm significant predictor neoplastic polyp conclusion polyp size 15 mm strongest predictor neoplastic polyp us hyperechoic foci polyp ct visibility useful indicators differentiation neoplastic polyp addition established predictors key points polyp size 15 mm strongest predictor neoplastic polyp us hyperechoic foci polyp ct visibility new predictors rate malignancy low polyps even 10 mm larger 15 1 stn","probabilities":0.9799733,"Title":"Us Characteristics For The Prediction Of Neoplasm In Gallbladder Polyps 10 Mm Or Larger","Abstract":"Purpose: To evaluate the characteristics of gallbladder polyps 10 mm or larger to predict a neoplasm in US examinations. \n\n Materials and methods: Fifty-three patients with gallbladder polyps ≥ 10 mm with follow-up images or pathologic diagnosis were included in the retrospective study. All images and reports were reviewed to determine the imaging characteristics of gallbladder polyps. Univariate and multivariate analyses were used to evaluate predictors for a neoplastic polyp. \n\n Results: A neoplastic polyp was verified in 12 of 53 patients and the mean size was 13.9 mm. The univariate analysis revealed that adjacent gallbladder wall thickening, larger size (≥15 mm), older age (≥57 years), absence of hyperechoic foci in a polyp, CT visibility, sessile shape, a solitary polyp, and an irregular surface were significant predictors for a neoplastic polyp. In the multivariate analysis, larger size (≥15 mm) was a significant predictor for a neoplastic polyp. \n\n Conclusion: A polyp size ≥15 mm was the strongest predictor for a neoplastic polyp with US. The hyperechoic foci in a polyp and CT visibility would be useful indicators for the differentiation of a neoplastic polyp, in addition to the established predictors. \n\n Key points: • A polyp size ≥15 mm is the strongest predictor for a neoplastic polyp with US. • Hyperechoic foci in a polyp and CT visibility are new predictors. • The rate of malignancy is low in polyps even 10 mm or larger (15.1 %).","Source":"STN","category":"HUMAN","training_data":"Us Characteristics For The Prediction Of Neoplasm In Gallbladder Polyps 10 Mm Or Larger Purpose: To evaluate the characteristics of gallbladder polyps 10 mm or larger to predict a neoplasm in US examinations. \n\n Materials and methods: Fifty-three patients with gallbladder polyps ≥ 10 mm with follow-up images or pathologic diagnosis were included in the retrospective study. All images and reports were reviewed to determine the imaging characteristics of gallbladder polyps. Univariate and multivariate analyses were used to evaluate predictors for a neoplastic polyp. \n\n Results: A neoplastic polyp was verified in 12 of 53 patients and the mean size was 13.9 mm. The univariate analysis revealed that adjacent gallbladder wall thickening, larger size (≥15 mm), older age (≥57 years), absence of hyperechoic foci in a polyp, CT visibility, sessile shape, a solitary polyp, and an irregular surface were significant predictors for a neoplastic polyp. In the multivariate analysis, larger size (≥15 mm) was a significant predictor for a neoplastic polyp. \n\n Conclusion: A polyp size ≥15 mm was the strongest predictor for a neoplastic polyp with US. The hyperechoic foci in a polyp and CT visibility would be useful indicators for the differentiation of a neoplastic polyp, in addition to the established predictors. \n\n Key points: • A polyp size ≥15 mm is the strongest predictor for a neoplastic polyp with US. • Hyperechoic foci in a polyp and CT visibility are new predictors. • The rate of malignancy is low in polyps even 10 mm or larger (15.1 %). STN","prediction_labels":"HUMAN"},{"cleaned":"cox 2 overexpression resected pancreatic head adenocarcinomas correlates favourable prognosis background overexpression cyclooxygenase 2 cox 2 implicated oncogenesis progression adenocarcinomas pancreatic head data prognostic importance cox expression tumours inconsistent conflicting evaluated cox 2 overexpression affected overall postoperative survival pancreatic head adenocarcinomas methods study included 230 consecutive pancreatoduodenectomies pancreatic cancer pc n 92 ampullary cancer ac n 62 distal bile duct cancer dbc n 76 cox 2 expression assessed immunohistochemistry associations cox 2 expression histopathologic variables including degree differentiation histopathologic type differentiation pancreatobiliary vs intestinal lymph node ratio lnr evaluated unadjusted adjusted survival analysis performed results cox 2 staining positive 71 pc 77 ac 72 dbc irrespective tumour origin overall patient survival favourable patients cox 2 positive tumours cox 2 negative p 0 043 pc p 0 011 ac p 0 06 dbc tumours pancreatobiliary type histopathological differentiation cox 2 expression significantly affect overall patient survival ac intestinal differentiation cox 2 expression significantly predicted favourable survival p 0 003 pc cox 2 expression significantly associated high degree differentiation p 0 002 cox 2 lnr independently predicted good prognosis multivariate model conclusions cox 2 overexpressed pancreatic cancer ampullary cancer distal bile duct cancer confers survival benefit three cancer types pancreatic cancer cox 2 overexpression significantly associated degree differentiation independently predicts favourable prognosis stn","probabilities":0.9799733,"Title":"Cox-2 Overexpression In Resected Pancreatic Head Adenocarcinomas Correlates With Favourable Prognosis","Abstract":"Background: Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas. \r\n\r\n Methods: The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n = 92), ampullary cancer (AC, n = 62) and distal bile duct cancer (DBC, n = 76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed. \r\n\r\n Results: COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p = 0.043 in PC, p = 0.011 in AC, p = 0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p = 0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model. \r\n\r\n Conclusions: COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis.","Source":"STN","category":"HUMAN","training_data":"Cox-2 Overexpression In Resected Pancreatic Head Adenocarcinomas Correlates With Favourable Prognosis Background: Overexpression of cyclooxygenase-2 (COX-2) has been implicated in oncogenesis and progression of adenocarcinomas of the pancreatic head. The data on the prognostic importance of COX expression in these tumours is inconsistent and conflicting. We evaluated how COX-2 overexpression affected overall postoperative survival in pancreatic head adenocarcinomas. \r\n\r\n Methods: The study included 230 consecutive pancreatoduodenectomies for pancreatic cancer (PC, n = 92), ampullary cancer (AC, n = 62) and distal bile duct cancer (DBC, n = 76). COX-2 expression was assessed by immunohistochemistry. Associations between COX-2 expression and histopathologic variables including degree of differentiation, histopathologic type of differentiation (pancreatobiliary vs. intestinal) and lymph node ratio (LNR) were evaluated. Unadjusted and adjusted survival analysis was performed. \r\n\r\n Results: COX-2 staining was positive in 71% of PC, 77% in AC and 72% in DBC. Irrespective of tumour origin, overall patient survival was more favourable in patients with COX-2 positive tumours than COX-2 negative (p = 0.043 in PC, p = 0.011 in AC, p = 0.06 in DBC). In tumours of pancreatobiliary type of histopathological differentiation, COX-2 expression did not significantly affect overall patient survival. In AC with intestinal differentiation COX-2 expression significantly predicted favourable survival (p = 0.003). In PC, COX-2 expression was significantly associated with high degree of differentiation (p = 0.002). COX-2 and LNR independently predicted good prognosis in a multivariate model. \r\n\r\n Conclusions: COX-2 is overexpressed in pancreatic cancer, ampullary cancer and distal bile duct cancer and confers a survival benefit in all three cancer types. In pancreatic cancer, COX-2 overexpression is significantly associated with the degree of differentiation and independently predicts a favourable prognosis. STN","prediction_labels":"HUMAN"},{"cleaned":"trends 5 year relative survival rates intrahepatic cholangiocarcinoma us introduction intrahepatic cholangiocarcinoma icc aggressive cancer increasing incidence rates purpose study investigate impact sex race ethnicity 5 year relative survival rate individuals age 20 using surveillance epidemiology end results seer database 1992 2011 methods patients diagnosed icc 1992 2011 identified seer registry 5 year relative survival rates icc us calculated different time intervals consisting 1992 1996 1997 2001 2002 2006 2007 2011 ethnic groups used analysis consisted black white included american indians alaskans asian pacific islanders results black men highest 5 year relative survival rate 11 9 2007 2011 5 year relative survival rate 5 50 6 1 white men men denoted category respectively 2007 2011 5 year relative survival rate decreased 2002 2006 2007 2011 white men men however increased black men 2002 2006 5 year relative survival rate 6 60 white men 8 3 men 2007 2011 5 year survival rate 5 50 white men 6 1 men white men lowest 5 year relative survival rate amongst ethnic groups women 5 year survival rate highest black women 10 8 2007 2011 5 year survival rate increased years 1992 2011 ethnic groups comparing women decrease 5 year relative survival rate 11 40 10 60 2002 2006 2007 2011 women white women lowest 5 year relative survival rate 2002 2011 comparison ethnic groups google scholar","probabilities":0.9799733,"Title":"Trends In 5-Year Relative Survival Rates For Intrahepatic Cholangiocarcinoma In The Us","Abstract":"Introduction: Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer with increasing incidence rates. The purpose of this study is to investigate the impact of sex, and race/ethnicity on the 5-year relative survival rate for individuals above the age of 20 using the Surveillance, Epidemiology, and End Results (SEER) database from 1992-2011.\nMethods: Patients diagnosed with ICC from 1992-2011 were identified from the SEER Registry. The 5-year relative survival rates of ICC in the US were calculated during different time intervals consisting of 1992-1996, 1997-2001, 2002-2006, and 2007-2011. The ethnic groups used in this analysis consisted of black, white, and other where “other” included American Indians, Alaskans and Asian/Pacific Islanders.\nResults: Black men had the highest 5-year relative survival rate at 11.9% from 2007-2011. The 5-year relative survival rate was 5.50% and 6.1% for white men and men denoted in the other category, respectively from 2007-2011. The 5-year relative survival rate has decreased from 2002-2006 to 2007-2011 for white men and “other” men, however it has increased for black men. In 2002-2006, the 5-year relative survival rate was 6.60% for white men, and 8.3% for “other” men. In 2007-2011, the 5-year survival rate was 5.50% for white men, and 6.1% for “other” men. White men had the lowest 5-year relative survival rate amongst all ethnic groups. For women, the 5-year survival rate is highest for black women at 10.8% from 2007-2011. The 5-year survival rate has increased over the years from 1992-2011 for most ethnic groups when comparing women. There was a decrease in 5-year relative survival rate of 11.40% to 10.60% from 2002-2006 and 2007-2011 for “other” women. White women had the lowest 5-year relative survival rate from 2002-2011 in comparison to other ethnic groups.","Source":"Google Scholar","category":"HUMAN","training_data":"Trends In 5-Year Relative Survival Rates For Intrahepatic Cholangiocarcinoma In The Us Introduction: Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer with increasing incidence rates. The purpose of this study is to investigate the impact of sex, and race/ethnicity on the 5-year relative survival rate for individuals above the age of 20 using the Surveillance, Epidemiology, and End Results (SEER) database from 1992-2011.\nMethods: Patients diagnosed with ICC from 1992-2011 were identified from the SEER Registry. The 5-year relative survival rates of ICC in the US were calculated during different time intervals consisting of 1992-1996, 1997-2001, 2002-2006, and 2007-2011. The ethnic groups used in this analysis consisted of black, white, and other where “other” included American Indians, Alaskans and Asian/Pacific Islanders.\nResults: Black men had the highest 5-year relative survival rate at 11.9% from 2007-2011. The 5-year relative survival rate was 5.50% and 6.1% for white men and men denoted in the other category, respectively from 2007-2011. The 5-year relative survival rate has decreased from 2002-2006 to 2007-2011 for white men and “other” men, however it has increased for black men. In 2002-2006, the 5-year relative survival rate was 6.60% for white men, and 8.3% for “other” men. In 2007-2011, the 5-year survival rate was 5.50% for white men, and 6.1% for “other” men. White men had the lowest 5-year relative survival rate amongst all ethnic groups. For women, the 5-year survival rate is highest for black women at 10.8% from 2007-2011. The 5-year survival rate has increased over the years from 1992-2011 for most ethnic groups when comparing women. There was a decrease in 5-year relative survival rate of 11.40% to 10.60% from 2002-2006 and 2007-2011 for “other” women. White women had the lowest 5-year relative survival rate from 2002-2011 in comparison to other ethnic groups. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"alpha methylacyl coenzyme racemase overexpression gallbladder carcinoma confers independent prognostic indicator aims increased oxidation branched chain fatty acids provides additional metabolic advantage cancer cells thereby enhancing tumour development progression alpha methylacyl coenzyme racemase amacr enzyme essential catabolism branched chain fatty acids allows subsequent oxidation thus plays important role generating biological energy however expression amacr never systemically investigated gallbladder carcinoma study evaluated expression status associations clinicopathological variables prognostic implications amacr well defined cohort gallbladder carcinoma confirmed expression status gallbladder carcinoma cells methods amacr immunostaining assessable 89 cases tissue microarrays gallbladder carcinoma correlated clinicopathological factors patient survival three gallbladder carcinoma cell lines one non tumorigenic cholangiocyte amacr mrna expression measured real time reverse transcription pcr endogenous expression amacr protein analysed western blotting results amacr overexpression significantly associated advanced primary tumour status p 0 027 american joint committee cancer stage p 0 027 increased histological grade p 0 002 vascular invasion p 0 017 importantly amacr overexpression independently predicted worse disease specific survival p 0 0452 rr 1 887 expression levels amacr mrna total protein various cells comparable abundance amacr expression increased tumour cells even higher metastatic cell line conclusions primary gallbladder carcinoma amacr overexpression correlated important prognosticators independently portended worse outcomes highlighting potential prognostic therapeutic utility amacr gallbladder carcinoma stn","probabilities":0.54545456,"Title":"Alpha-Methylacyl Coenzyme A Racemase Overexpression In Gallbladder Carcinoma Confers An Independent Prognostic Indicator","Abstract":"Aims: Increased β-oxidation of branched-chain fatty acids provides an additional metabolic advantage for cancer cells thereby enhancing tumour development and progression. Alpha-methylacyl coenzyme A racemase (AMACR) is an enzyme essential for the catabolism of branched-chain fatty acids that allows their subsequent β-oxidation and thus plays an important role in generating biological energy. However, the expression of AMACR has never been systemically investigated in gallbladder carcinoma. This study evaluated the expression status, associations with clinicopathological variables and prognostic implications of AMACR in a well-defined cohort of gallbladder carcinoma and confirmed their expression status in gallbladder carcinoma cells. \r\n\r\n Methods: AMACR immunostaining was assessable in 89 cases on tissue microarrays of gallbladder carcinoma, and it was correlated with clinicopathological factors and patient survival. In three gallbladder carcinoma cell lines and one non-tumorigenic cholangiocyte, AMACR mRNA expression was measured by real-time reverse transcription PCR and the endogenous expression of AMACR protein was analysed by western blotting. \r\n\r\n Results: AMACR overexpression was significantly associated with an advanced primary tumour status (p=0.027) and American Joint Committee on Cancer stage (p=0.027), an increased histological grade (p=0.002) and vascular invasion (p=0.017). Importantly, AMACR overexpression independently predicted worse disease-specific survival (p=0.0452, RR 1.887). Expression levels of AMACR mRNA and total protein in various cells were comparable. The abundance of AMACR expression increased in tumour cells and was even higher in the metastatic cell line. \r\n\r\n Conclusions: In primary gallbladder carcinoma, AMACR overexpression was correlated with important prognosticators and independently portended worse outcomes, highlighting the potential prognostic and therapeutic utility of AMACR in gallbladder carcinoma.","Source":"STN","category":"ANIMAL","training_data":"Alpha-Methylacyl Coenzyme A Racemase Overexpression In Gallbladder Carcinoma Confers An Independent Prognostic Indicator Aims: Increased β-oxidation of branched-chain fatty acids provides an additional metabolic advantage for cancer cells thereby enhancing tumour development and progression. Alpha-methylacyl coenzyme A racemase (AMACR) is an enzyme essential for the catabolism of branched-chain fatty acids that allows their subsequent β-oxidation and thus plays an important role in generating biological energy. However, the expression of AMACR has never been systemically investigated in gallbladder carcinoma. This study evaluated the expression status, associations with clinicopathological variables and prognostic implications of AMACR in a well-defined cohort of gallbladder carcinoma and confirmed their expression status in gallbladder carcinoma cells. \r\n\r\n Methods: AMACR immunostaining was assessable in 89 cases on tissue microarrays of gallbladder carcinoma, and it was correlated with clinicopathological factors and patient survival. In three gallbladder carcinoma cell lines and one non-tumorigenic cholangiocyte, AMACR mRNA expression was measured by real-time reverse transcription PCR and the endogenous expression of AMACR protein was analysed by western blotting. \r\n\r\n Results: AMACR overexpression was significantly associated with an advanced primary tumour status (p=0.027) and American Joint Committee on Cancer stage (p=0.027), an increased histological grade (p=0.002) and vascular invasion (p=0.017). Importantly, AMACR overexpression independently predicted worse disease-specific survival (p=0.0452, RR 1.887). Expression levels of AMACR mRNA and total protein in various cells were comparable. The abundance of AMACR expression increased in tumour cells and was even higher in the metastatic cell line. \r\n\r\n Conclusions: In primary gallbladder carcinoma, AMACR overexpression was correlated with important prognosticators and independently portended worse outcomes, highlighting the potential prognostic and therapeutic utility of AMACR in gallbladder carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"evaluation hormonal growth factor receptor expression clinicopathological correlation carcinoma gallbladder way forward abstract introduction north india reports one highest incidence gallbladder cancer gbc world common type biliary tract cancer marked gender bias female sex affecting women 2 6 times frequently men studies evaluating biomolecular marker profile gbc aims objectives study carried immunohistochemically determine hormone receptor estrogen receptor er progesterone receptor pr growth factor receptors 2 neu egfr 1 expression level patients gbc study clinicopathological correlation methods materials study group comprised 50 cases 8 male 42 female histologically proven gbc immunohistochemical expression receptors er pr egfr 1and 2 neu quantified using standard protocol guidelines based percentage intensity cell staining line 2 neu status determination guidelines proposed gastric cancer ga study results 50 patients 30 patients presented locally advanced metastatic disease underwent palliative chemotherapy 20 patients underwent radical cholecystectomy followed adjuvant chemotherapy histology predominantly adenocarcinoma 47 50 er consistently negative immunohistochemical staining 48 50 96 patients pr positive 22 50 44 patients 2 neu receptor strongly positive 24 50 48 negative 18 50 36 equivocal 8 patients egfr 1 strongly positive 16 50 32 patients conclusions gbc associated late diagnosis unsatisfactory treatment poor prognosis clearly new therapeutic regimens need hour based evolving understanding molecular biology carcinogenic mechanisms underlying development gbc role targeted therapy 2 neu egfr 1 receptor needs evaluation gbc prove dawn new era orphan tumors gbc keywords carcinoma gallbladder immunohistochemistry clinicopathological google scholar","probabilities":1.0,"Title":"Evaluation Of Hormonal And Growth Factor Receptor Expression And Its Clinicopathological Correlation In Carcinoma Gallbladder Is It The Way Forward?","Abstract":"Abstract: Introduction: North India reports one of the highest incidence\nof gallbladder cancer (GBC) in the world. It is the most common\ntype of biliary tract cancer with marked gender bias for female sex,\naffecting women 2-6 times more frequently than men. There are very\nfew studies evaluating biomolecular marker profile of GBC. Aims/Objectives:\nThis study was carried out to immunohistochemically determine\nthe Hormone receptor (Estrogen receptor(ER) and Progesterone\nreceptor(PR)) and Growth factor receptors (Her-2/neu and EGFR-1)\nexpression level in patients of GBC and to study its clinicopathological\ncorrelation. Methods (Materials): The study group comprised of 50\ncases (8 male and 42 female) of histologically proven GBC. Immunohistochemical\nexpression of receptors ER, PR, EGFR-1and HER-2/neu\nwas quantified using standard protocol and guidelines based on percentage\nand the intensity of cell staining. This was in line with Her-\n2/neu status determination guidelines proposed for gastric cancer (To-\nGA study). Results: Of the 50 patients, 30 patients presented with\nlocally advanced/metastatic disease and underwent palliative chemotherapy\nwhile 20 patients underwent radical cholecystectomy followed\nby adjuvant chemotherapy. Histology was predominantly adenocarcinoma\n(47/50). ER was consistently negative on immunohistochemical\nstaining 48/50 (96 %) patients, while PR was positive in 22/50 (44 %)\nof the patients. Her-2/neu receptor was strongly positive in 24/50\n(48 %), negative in 18/50 (36 %) and equivocal in 8 patients. EGFR-\n1 was strongly positive in 16/50 (32 %) patients. Conclusions: GBC is\nassociated with late diagnosis, unsatisfactory treatment and poor prognosis.\nClearly, new therapeutic regimens are the need of the hour, based\non our evolving understanding of molecular biology and carcinogenic\nmechanisms underlying development of GBC. Role of targeted therapy\nagainst Her-2/neu and EGFR-1 receptor needs further evaluation in\nGBC and could prove to be the dawn of a new era in orphan tumors\nsuch as GBC. Keywords: carcinoma gallbladder, immunohistochemistry,\nclinicopathological","Source":"Google Scholar","category":"HUMAN","training_data":"Evaluation Of Hormonal And Growth Factor Receptor Expression And Its Clinicopathological Correlation In Carcinoma Gallbladder Is It The Way Forward? Abstract: Introduction: North India reports one of the highest incidence\nof gallbladder cancer (GBC) in the world. It is the most common\ntype of biliary tract cancer with marked gender bias for female sex,\naffecting women 2-6 times more frequently than men. There are very\nfew studies evaluating biomolecular marker profile of GBC. Aims/Objectives:\nThis study was carried out to immunohistochemically determine\nthe Hormone receptor (Estrogen receptor(ER) and Progesterone\nreceptor(PR)) and Growth factor receptors (Her-2/neu and EGFR-1)\nexpression level in patients of GBC and to study its clinicopathological\ncorrelation. Methods (Materials): The study group comprised of 50\ncases (8 male and 42 female) of histologically proven GBC. Immunohistochemical\nexpression of receptors ER, PR, EGFR-1and HER-2/neu\nwas quantified using standard protocol and guidelines based on percentage\nand the intensity of cell staining. This was in line with Her-\n2/neu status determination guidelines proposed for gastric cancer (To-\nGA study). Results: Of the 50 patients, 30 patients presented with\nlocally advanced/metastatic disease and underwent palliative chemotherapy\nwhile 20 patients underwent radical cholecystectomy followed\nby adjuvant chemotherapy. Histology was predominantly adenocarcinoma\n(47/50). ER was consistently negative on immunohistochemical\nstaining 48/50 (96 %) patients, while PR was positive in 22/50 (44 %)\nof the patients. Her-2/neu receptor was strongly positive in 24/50\n(48 %), negative in 18/50 (36 %) and equivocal in 8 patients. EGFR-\n1 was strongly positive in 16/50 (32 %) patients. Conclusions: GBC is\nassociated with late diagnosis, unsatisfactory treatment and poor prognosis.\nClearly, new therapeutic regimens are the need of the hour, based\non our evolving understanding of molecular biology and carcinogenic\nmechanisms underlying development of GBC. Role of targeted therapy\nagainst Her-2/neu and EGFR-1 receptor needs further evaluation in\nGBC and could prove to be the dawn of a new era in orphan tumors\nsuch as GBC. Keywords: carcinoma gallbladder, immunohistochemistry,\nclinicopathological Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"neoadjuvant chemoradiotherapy followed liver transplantation unresectable cholangiocarcinoma single centre national experience background unresectable cholangiocarcinoma cca dismal prognosis initial studies orthotopic liver transplantation olt alone cca yielded disappointing outcomes mayo clinic demonstrated long term survival using neoadjuvant chemoradiotherapy followed olt selected patients unresectable cca study reports irish national liver transplant programme experience neoadjuvant therapy olt unresectable cca materials methods twenty seven patients cca selected neoadjuvant chemoradiotherapy single centre october 2004 september 2011 patients given brachytherapy external beam radiotherapy 5 fluorouracil 5 fu followed liver transplantation progression free 20 patients results twenty progression free patients neoadjuvant therapy underwent olt hospital mortality 20 16 patients left hospital survival rates 94 61 1 4 years seven patients developed recurrent disease died intervals 10 58 months olt whereas 9 disease free median follow 37 months 18 76 predictors disease recurrence tumour explant specimen high ca 19 9 levels discussion selected patients unresectable cca long term survival achieved using neoadjuvant chemoradiotherapy olt although short term mortality high prospective international registries may aid patient selection refinement neoadjuvant regimens pubmed","probabilities":0.9799733,"Title":"Neoadjuvant chemoradiotherapy followed by liver transplantation for unresectable cholangiocarcinoma: a single-centre national experience","Abstract":"BACKGROUND: Unresectable cholangiocarcinoma (CCA) has a dismal prognosis. Initial studies of orthotopic liver transplantation (OLT) alone for CCA yielded disappointing outcomes. The Mayo Clinic demonstrated long-term survival using neoadjuvant chemoradiotherapy followed by OLT in selected patients with unresectable CCA. This study reports the Irish National Liver Transplant Programme experience of neoadjuvant therapy and OLT for unresectable CCA. MATERIALS AND METHODS: Twenty-seven patients with CCA were selected for neoadjuvant chemoradiotherapy in a single centre from October 2004 to September 2011. Patients were given brachytherapy, external beam radiotherapy and 5-fluorouracil (5-Fu), followed by liver transplantation if progression free (20 patients). RESULTS: Twenty progression-free patients after neoadjuvant therapy underwent OLT. Hospital mortality was 20%. Of the 16 patients who left hospital, survival rates were 94% and 61% at 1 and 4 years. Seven patients developed recurrent disease and died at intervals of 10-58 months after OLT, whereas 9 are disease free with a median follow-up of 37 months (18-76). Predictors of disease recurrence were a tumour in explant specimen and high CA 19.9 levels. DISCUSSION: In selected patients with unresectable CCA, long-term survival can be achieved using neoadjuvant chemoradiotherapy and OLT although short-term mortality is high. Prospective international registries may aid patient selection and refinement of neoadjuvant regimens.","Source":"PubMed","category":"HUMAN","training_data":"Neoadjuvant chemoradiotherapy followed by liver transplantation for unresectable cholangiocarcinoma: a single-centre national experience BACKGROUND: Unresectable cholangiocarcinoma (CCA) has a dismal prognosis. Initial studies of orthotopic liver transplantation (OLT) alone for CCA yielded disappointing outcomes. The Mayo Clinic demonstrated long-term survival using neoadjuvant chemoradiotherapy followed by OLT in selected patients with unresectable CCA. This study reports the Irish National Liver Transplant Programme experience of neoadjuvant therapy and OLT for unresectable CCA. MATERIALS AND METHODS: Twenty-seven patients with CCA were selected for neoadjuvant chemoradiotherapy in a single centre from October 2004 to September 2011. Patients were given brachytherapy, external beam radiotherapy and 5-fluorouracil (5-Fu), followed by liver transplantation if progression free (20 patients). RESULTS: Twenty progression-free patients after neoadjuvant therapy underwent OLT. Hospital mortality was 20%. Of the 16 patients who left hospital, survival rates were 94% and 61% at 1 and 4 years. Seven patients developed recurrent disease and died at intervals of 10-58 months after OLT, whereas 9 are disease free with a median follow-up of 37 months (18-76). Predictors of disease recurrence were a tumour in explant specimen and high CA 19.9 levels. DISCUSSION: In selected patients with unresectable CCA, long-term survival can be achieved using neoadjuvant chemoradiotherapy and OLT although short-term mortality is high. Prospective international registries may aid patient selection and refinement of neoadjuvant regimens. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical value fibulin 1 prognosis prospective mechanism intrahepatic cholangiocarcinoma background intrahepatic cholangiocarcinoma icc second common malignancy arising liver fibulin 1 demonstrated involved various cancers however role icc remains unclear methods study clinical value potential molecular mechanism fibulin 1 icc immunohistochemistry bioinformatic analyses performed using data gene expression omnibus datasets cancer genome atlas database results fibulin 1 expression overexpressed icc tissues compared adjacent non cancerous tissues significantly associated unfavorable overall survival moreover similar genes identified gene expression profiling interactive analysis microarray data set next functional pathway enrichment analysis demonstrated fibulin 1 overrepresented pathways extracellular matrix organization angiogenesis associated tumor progression potential metastasis gene set enrichment analysis indicated gene sets epithelial mesenchymal transition tgf beta signaling pathway angiogenesis enriched tissues high fibulin 1 level furthermore fibulin 1 silencing suppressed ability icc tumor cells form colonies sifibulin 1 repressed endogenous protein level p akt conclusion collectively study suggests fibulin 1 overexpression may play key roles carcinogenesis progression icc via regulation tumor related pathways pubmed","probabilities":0.88235295,"Title":"The clinical value of Fibulin-1 for prognosis and its prospective mechanism in intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy arising from the liver. Fibulin-1 has been demonstrated to be involved in various cancers, however, its role in ICC remains unclear. METHODS: To study the clinical value and potential molecular mechanism of Fibulin-1 in ICC, immunohistochemistry and bioinformatic analyses were performed using data in the Gene Expression Omnibus Datasets and The Cancer Genome Atlas database. RESULTS: Fibulin-1 expression was overexpressed in ICC tissues compared with adjacent non-cancerous tissues, and was significantly associated with unfavorable overall survival. Moreover, similar genes were identified by Gene Expression Profiling Interactive Analysis and microarray data set. Next, functional and pathway enrichment analysis demonstrated that Fibulin-1 was overrepresented in the pathways of extracellular matrix organization and angiogenesis, which are associated with tumor progression and potential for metastasis. Gene set enrichment analysis indicated that the gene sets of epithelial mesenchymal transition, TGF-beta signaling pathway and angiogenesis were enriched in tissues with high Fibulin-1 level. Furthermore, Fibulin-1 silencing suppressed the ability of ICC tumor cells to form colonies and siFibulin-1 repressed the endogenous protein level of p-AKT. CONCLUSION: Collectively, this study suggests that Fibulin-1 overexpression may play key roles in the carcinogenesis and progression of ICC via regulation of tumor-related pathways.","Source":"PubMed","category":"HUMAN","training_data":"The clinical value of Fibulin-1 for prognosis and its prospective mechanism in intrahepatic cholangiocarcinoma BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common malignancy arising from the liver. Fibulin-1 has been demonstrated to be involved in various cancers, however, its role in ICC remains unclear. METHODS: To study the clinical value and potential molecular mechanism of Fibulin-1 in ICC, immunohistochemistry and bioinformatic analyses were performed using data in the Gene Expression Omnibus Datasets and The Cancer Genome Atlas database. RESULTS: Fibulin-1 expression was overexpressed in ICC tissues compared with adjacent non-cancerous tissues, and was significantly associated with unfavorable overall survival. Moreover, similar genes were identified by Gene Expression Profiling Interactive Analysis and microarray data set. Next, functional and pathway enrichment analysis demonstrated that Fibulin-1 was overrepresented in the pathways of extracellular matrix organization and angiogenesis, which are associated with tumor progression and potential for metastasis. Gene set enrichment analysis indicated that the gene sets of epithelial mesenchymal transition, TGF-beta signaling pathway and angiogenesis were enriched in tissues with high Fibulin-1 level. Furthermore, Fibulin-1 silencing suppressed the ability of ICC tumor cells to form colonies and siFibulin-1 repressed the endogenous protein level of p-AKT. CONCLUSION: Collectively, this study suggests that Fibulin-1 overexpression may play key roles in the carcinogenesis and progression of ICC via regulation of tumor-related pathways. PubMed","prediction_labels":"HUMAN"},{"cleaned":"guggulsterone inhibits human cholangiocarcinoma sk cha 1 mz cha 1 cell growth inducing caspase dependent apoptosis downregulation survivin bcl 2 expression guggulsterone recently reported demonstrate anti tumor effects variety cancers present study aims investigate biological roles underlying mechanism action guggulsterone cholangiocarcinoma immortalized human cholangiocarcinoma sk cha 1 mz cha 1 cell lines treated various concentrations trans isomer guggulsterone z guggulsterone cellular proliferation determined using xtt assay apoptotic status cholangiocarcinoma cells assessed hoechst 33258 staining dna fragmentation assay ow cytometry specific caspase inhibitor used explore role caspase guggulsterone induced apoptosis colorimetric assay performed measure alterations activities caspase 3 8 9 western blot analysis used detect protein expression survivin b cell lymphoma 2 bcl 2 bcl 2 associated x protein cleaved poly adenosine diphosphate ribose polymerase parp revealed present data guggulsterone significantly inhibited growth two human cholangiocarcinoma cell lines inducing cellular apoptosis addition guggulsterone induced apoptosis cholangiocarcinoma cells demonstrated partially inhibited caspase inhibitors z vad fmk z lehd fmk z ietd fmk accompanied activation caspases 3 8 9 accumulation cleaved parp decreased expression survivin bcl 2 conclusion present study demonstrated guggulsterone able suppress proliferation cholangiocarcinoma inducing caspase dependent apoptosis downregulating survivin bcl 2 stn","probabilities":0.9467213,"Title":"Guggulsterone Inhibits Human Cholangiocarcinoma Sk-Cha-1 And Mz-Cha-1 Cell Growth By Inducing Caspase-Dependent Apoptosis And Downregulation Of Survivin And Bcl-2 Expression","Abstract":"Guggulsterone has recently been reported to demonstrate anti-tumor effects in a variety of cancers. The present study aims to investigate the biological roles and underlying mechanism of the action of guggulsterone in cholangiocarcinoma. The immortalized human cholangiocarcinoma Sk-ChA-1 and Mz-ChA-1 cell lines were treated with various concentrations of the trans isomer of guggulsterone, Z-guggulsterone. Cellular proliferation was determined using the XTT assay. The apoptotic status of cholangiocarcinoma cells was assessed by Hoechst 33258 staining, DNA fragmentation assay and flow cytometry. Specific caspase inhibitor was used to explore the role of caspase in guggulsterone-induced apoptosis. A colorimetric assay was performed to measure the alterations of the activities of caspase-3, -8 and -9. Western blot analysis was used to detect the protein expression of survivin, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein and cleaved poly (adenosine diphosphate-ribose) polymerase (PARP). As revealed by the present data, guggulsterone significantly inhibited the growth of the two human cholangiocarcinoma cell lines by inducing cellular apoptosis. In addition, guggulsterone-induced apoptosis of cholangiocarcinoma cells was demonstrated to be partially inhibited by the caspase inhibitors z-VAD-fmk, z-LEHD-fmk and z-IETD-fmk, accompanied by the activation of caspases-3, -8 and -9, accumulation of cleaved PARP and decreased expression of survivin and Bcl-2. In conclusion, the present study demonstrated that guggulsterone was able to suppress the proliferation of cholangiocarcinoma by inducing caspase-dependent apoptosis and downregulating survivin and Bcl-2.","Source":"STN","category":"ANIMAL","training_data":"Guggulsterone Inhibits Human Cholangiocarcinoma Sk-Cha-1 And Mz-Cha-1 Cell Growth By Inducing Caspase-Dependent Apoptosis And Downregulation Of Survivin And Bcl-2 Expression Guggulsterone has recently been reported to demonstrate anti-tumor effects in a variety of cancers. The present study aims to investigate the biological roles and underlying mechanism of the action of guggulsterone in cholangiocarcinoma. The immortalized human cholangiocarcinoma Sk-ChA-1 and Mz-ChA-1 cell lines were treated with various concentrations of the trans isomer of guggulsterone, Z-guggulsterone. Cellular proliferation was determined using the XTT assay. The apoptotic status of cholangiocarcinoma cells was assessed by Hoechst 33258 staining, DNA fragmentation assay and flow cytometry. Specific caspase inhibitor was used to explore the role of caspase in guggulsterone-induced apoptosis. A colorimetric assay was performed to measure the alterations of the activities of caspase-3, -8 and -9. Western blot analysis was used to detect the protein expression of survivin, B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein and cleaved poly (adenosine diphosphate-ribose) polymerase (PARP). As revealed by the present data, guggulsterone significantly inhibited the growth of the two human cholangiocarcinoma cell lines by inducing cellular apoptosis. In addition, guggulsterone-induced apoptosis of cholangiocarcinoma cells was demonstrated to be partially inhibited by the caspase inhibitors z-VAD-fmk, z-LEHD-fmk and z-IETD-fmk, accompanied by the activation of caspases-3, -8 and -9, accumulation of cleaved PARP and decreased expression of survivin and Bcl-2. In conclusion, the present study demonstrated that guggulsterone was able to suppress the proliferation of cholangiocarcinoma by inducing caspase-dependent apoptosis and downregulating survivin and Bcl-2. STN","prediction_labels":"ANIMAL"},{"cleaned":"adiposity across adult life course incidence primary liver cancer nih aarp cohort obesity relatively late adulthood consistently associated increased risk primary liver cancer however little known role early adult adiposity evolution adiposity across adulthood hepatocarcinogenesis examined adult body mass index bmi kg m 2 relation hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc large prospective cohort weight ages 18 35 50 study baseline retrospectively reported 303 620 participants bmi trajectories identified using latent class trajectory modeling incidence hcc icc determined 2011 cox proportional hazards modeling used calculate adjusted hazard ratios hrs 95 confidence intervals cis total 372 hcc cases 104 icc cases occurred follow obese bmi 30 ages 18 35 50 baseline mean age 62 3 years range 50 3 71 5 years associated 86 119 elevated risk hcc bmi trajectories resulted obesity associated 80 higher hcc incidence bmi age 18 per 5 kg m 2 associated 34 higher risk icc association attenuated bmi older ages conclusion findings suggest maintaining healthy bmi throughout lifetime may reduce liver cancer risk future studies longitudinally collected weight information warranted elucidate role life course adiposity liver cancer development pubmed","probabilities":0.9799733,"Title":"Adiposity across the adult life course and incidence of primary liver cancer: The NIH-AARP cohort","Abstract":"Obesity relatively late in adulthood has been consistently associated with increased risk of primary liver cancer. However, little is known about the role of early adult adiposity and evolution of adiposity across adulthood in hepatocarcinogenesis. We examined adult body mass index (BMI; kg/m(2) ) in relation to hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a large prospective cohort. Weight at ages 18, 35, 50 and at study baseline was retrospectively reported by 303,620 participants. BMI trajectories were identified using latent class trajectory modeling. Incidence of HCC and ICC was determined through 2011. Cox proportional hazards modeling was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 372 HCC cases and 104 ICC cases occurred during follow-up. Being obese (BMI ≥ 30) at ages 18, 35, 50 and at baseline (mean age 62.3 years, range 50.3-71.5 years) was associated with an 86-119% elevated risk of HCC. BMI trajectories that resulted in obesity were associated with ∼80% higher HCC incidence. BMI at age 18, per 5 kg/m(2) , was associated with a 34% higher risk of ICC, but the association attenuated for BMI at older ages. In conclusion, our findings suggest that maintaining a healthy BMI throughout the lifetime may reduce liver cancer risk. Future studies with longitudinally collected weight information are warranted to further elucidate the role of life-course adiposity in liver cancer development.","Source":"PubMed","category":"HUMAN","training_data":"Adiposity across the adult life course and incidence of primary liver cancer: The NIH-AARP cohort Obesity relatively late in adulthood has been consistently associated with increased risk of primary liver cancer. However, little is known about the role of early adult adiposity and evolution of adiposity across adulthood in hepatocarcinogenesis. We examined adult body mass index (BMI; kg/m(2) ) in relation to hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) in a large prospective cohort. Weight at ages 18, 35, 50 and at study baseline was retrospectively reported by 303,620 participants. BMI trajectories were identified using latent class trajectory modeling. Incidence of HCC and ICC was determined through 2011. Cox proportional hazards modeling was used to calculate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 372 HCC cases and 104 ICC cases occurred during follow-up. Being obese (BMI ≥ 30) at ages 18, 35, 50 and at baseline (mean age 62.3 years, range 50.3-71.5 years) was associated with an 86-119% elevated risk of HCC. BMI trajectories that resulted in obesity were associated with ∼80% higher HCC incidence. BMI at age 18, per 5 kg/m(2) , was associated with a 34% higher risk of ICC, but the association attenuated for BMI at older ages. In conclusion, our findings suggest that maintaining a healthy BMI throughout the lifetime may reduce liver cancer risk. Future studies with longitudinally collected weight information are warranted to further elucidate the role of life-course adiposity in liver cancer development. PubMed","prediction_labels":"HUMAN"},{"cleaned":"body mass index risk incident gallbladder cancer results two large us prospective cohort studies background aims gallbladder cancer relatively rare malignancy highly lethal 5 year relative survival rate 15 men women cholesterol gallstones face higher risk disease little else known etiology obesity usually defined high body mass index bmi weight kg divided height meters squared greatly increases risk gallstones excess body mass emerges candidate risk factor gallbladder cancer lethality gallbladder cancer makes prospective studies useful date prospective studies inconsistent limited data suggest higher risks among obese women results among men equivocal rarity cancer motivated us combine cohorts derive stable risk estimates investigated association bmi incident gallbladder cancer risk two large u cohort studies methods american cancer society cancer prevention study ii nutrition cohort cps ii prospective study cancer incidence conducted among u men women resided 21 states population based state cancer registries 1992 1993 184 194 adult participants aged 40 93 years completed detailed self administered questionnaire included body weight physical activity lifestyle medical factors nih aarp diet health study prospective study men women aged 50 71 years six u states two metropolitan areas 1995 1996 566 401 adult participants completed self administered questionnaire regarding demographic lifestyle characteristics including body weight height cox proportional hazards regression analysis used calculate relative risks rr 95 confidence intervals ci association bmi incident gallbladder cancer risk study sex adjusting covariates included age baseline physical activity cigarette smoking random effects meta analysis used combine results results exclusions 154 493 73 174 men 81 319 women cps ii participants 479 593 192 095 men 287 498 women aarp participants remained final analytic cohorts among analytic cohort participants twenty men 50 women cps ii 59 men 53 women aarp diagnosed incident gallbladder cancer icd o 3 23 9 end follow june 2007 cps ii december 2006 aarp cps ii study suggestive association linear bmi per 5 kg m 2 gallbladder cancer risk although risk estimates statistically significant men rr 1 31 95 ci 0 75 2 28 women rr 1 15 95 ci 0 85 1 54 larger aarp cohort bmi per 5 kg m 2 positively associated risk gallbladder cancer men rr 1 18 95 ci 0 97 1 44 women rr 1 14 95 ci 1 03 1 25 pooled estimates random effects meta analysis found summary relative risks 5 kg m 2 bmi increase 1 19 men 95 ci 0 99 1 44 1 14 women 95 ci 1 04 1 25 1 15 men women combined 95 ci 1 06 1 25 conclusions results study suggest bmi positively associated risk incident gallbladder cancer among women men lack statistical precision study lack categorical comparisons obese versus normal bmi due small case numbers highlights necessity pooling data multiple prospective studies assess impact energy balance indicators risk rarer cancers google scholar","probabilities":0.9799733,"Title":"Body Mass Index And Risk Of Incident Gallbladder Cancer: Results From Two Large Us Prospective Cohort Studies","Abstract":"Background and Aims: Gallbladder cancer, a relatively rare malignancy, is highly lethal with a 5-year relative survival rate of 15%. Men and women with cholesterol gallstones face higher risk of the disease, and little else is known of its etiology. Because obesity, usually defined by a high body mass index (BMI: weight in kg divided by height in meters squared), greatly increases risk for gallstones, excess body mass emerges as a candidate risk factor for gallbladder cancer. The lethality of gallbladder cancer makes prospective studies most useful. To date, prospective studies have been inconsistent, but limited data suggest higher risks among obese women, while results among men have been equivocal. The rarity of the cancer motivated us to combine cohorts to derive more stable risk estimates. We investigated the association between BMI and incident gallbladder cancer risk in two large U.S. cohort studies.\nMethods: The American Cancer Society's Cancer Prevention Study II Nutrition Cohort (CPS-II) is a prospective study of cancer incidence conducted among U.S. men and women who resided in 21 states with population-based state cancer registries. In 1992 or 1993, 184,194 adult participants, aged 40 to 93 years, completed a detailed, self-administered questionnaire that included body weight, physical activity and other lifestyle and medical factors. The NIH-AARP Diet and Health Study is a prospective study of men and women, aged 50 to 71 years, from six U.S. states and two metropolitan areas. In 1995 or 1996, 566,401 adult participants completed a self-administered questionnaire regarding demographic and lifestyle characteristics, including body weight and height. Cox proportional hazards regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI) for the association between BMI and incident gallbladder cancer risk, by study and sex, adjusting for covariates that included age at baseline, physical activity and cigarette smoking. Random-effects meta-analysis was used to combine results.\nResults: After exclusions, 154,493 (73,174 men and 81,319 women) CPS-II participants and 479,593 (192,095 men and 287,498 women) AARP participants remained in the final analytic cohorts; among analytic cohort participants. Twenty men and 50 women in CPS-II and 59 men and 53 women in AARP were diagnosed with an incident gallbladder cancer (ICD-O-3: 23.9) by the end of follow-up in June 2007 (CPS-II) and December 2006 (AARP). In the CPS-II study, there was a suggestive association between linear BMI, per 5 kg/m⁁2, and gallbladder cancer risk, although the risk estimates were not statistically significant in men (RR 1.31; 95%CI 0.75–2.28) or in women (RR 1.15; 95%CI 0.85–1.54). In the larger AARP cohort, BMI per 5 kg/m⁁2 was positively associated with risk of gallbladder cancer in men (RR 1.18; 95%CI 0.97–1.44) and in women (RR 1.14; 95%CI 1.03–1.25). Pooled estimates, from random-effects meta-analysis, found summary relative risks for a 5 kg/m⁁2 BMI increase of 1.19 for men (95%CI 0.99–1.44), 1.14 for women (95%CI 1.04–1.25), and 1.15 for men and women combined (95%CI 1.06–1.25).\nConclusions: Results of this study suggest that BMI is positively associated with risk of incident gallbladder cancer among women and men. The lack of statistical precision in this study, and the lack of categorical comparisons for obese versus normal BMI due to small case numbers, highlights the necessity of pooling data from multiple prospective studies to assess the impact of energy balance indicators on risk of rarer cancers.","Source":"Google Scholar","category":"HUMAN","training_data":"Body Mass Index And Risk Of Incident Gallbladder Cancer: Results From Two Large Us Prospective Cohort Studies Background and Aims: Gallbladder cancer, a relatively rare malignancy, is highly lethal with a 5-year relative survival rate of 15%. Men and women with cholesterol gallstones face higher risk of the disease, and little else is known of its etiology. Because obesity, usually defined by a high body mass index (BMI: weight in kg divided by height in meters squared), greatly increases risk for gallstones, excess body mass emerges as a candidate risk factor for gallbladder cancer. The lethality of gallbladder cancer makes prospective studies most useful. To date, prospective studies have been inconsistent, but limited data suggest higher risks among obese women, while results among men have been equivocal. The rarity of the cancer motivated us to combine cohorts to derive more stable risk estimates. We investigated the association between BMI and incident gallbladder cancer risk in two large U.S. cohort studies.\nMethods: The American Cancer Society's Cancer Prevention Study II Nutrition Cohort (CPS-II) is a prospective study of cancer incidence conducted among U.S. men and women who resided in 21 states with population-based state cancer registries. In 1992 or 1993, 184,194 adult participants, aged 40 to 93 years, completed a detailed, self-administered questionnaire that included body weight, physical activity and other lifestyle and medical factors. The NIH-AARP Diet and Health Study is a prospective study of men and women, aged 50 to 71 years, from six U.S. states and two metropolitan areas. In 1995 or 1996, 566,401 adult participants completed a self-administered questionnaire regarding demographic and lifestyle characteristics, including body weight and height. Cox proportional hazards regression analysis was used to calculate relative risks (RR) and 95% confidence intervals (CI) for the association between BMI and incident gallbladder cancer risk, by study and sex, adjusting for covariates that included age at baseline, physical activity and cigarette smoking. Random-effects meta-analysis was used to combine results.\nResults: After exclusions, 154,493 (73,174 men and 81,319 women) CPS-II participants and 479,593 (192,095 men and 287,498 women) AARP participants remained in the final analytic cohorts; among analytic cohort participants. Twenty men and 50 women in CPS-II and 59 men and 53 women in AARP were diagnosed with an incident gallbladder cancer (ICD-O-3: 23.9) by the end of follow-up in June 2007 (CPS-II) and December 2006 (AARP). In the CPS-II study, there was a suggestive association between linear BMI, per 5 kg/m⁁2, and gallbladder cancer risk, although the risk estimates were not statistically significant in men (RR 1.31; 95%CI 0.75–2.28) or in women (RR 1.15; 95%CI 0.85–1.54). In the larger AARP cohort, BMI per 5 kg/m⁁2 was positively associated with risk of gallbladder cancer in men (RR 1.18; 95%CI 0.97–1.44) and in women (RR 1.14; 95%CI 1.03–1.25). Pooled estimates, from random-effects meta-analysis, found summary relative risks for a 5 kg/m⁁2 BMI increase of 1.19 for men (95%CI 0.99–1.44), 1.14 for women (95%CI 1.04–1.25), and 1.15 for men and women combined (95%CI 1.06–1.25).\nConclusions: Results of this study suggest that BMI is positively associated with risk of incident gallbladder cancer among women and men. The lack of statistical precision in this study, and the lack of categorical comparisons for obese versus normal BMI due to small case numbers, highlights the necessity of pooling data from multiple prospective studies to assess the impact of energy balance indicators on risk of rarer cancers. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinicopathologic features surgical outcomes neuroendocrine carcinoma gallbladder neuroendocrine carcinoma nec gallbladder highly aggressive poor prognosis even curative resection purpose study collate analyze published data clarify surgical outcome nec gallbladder relationships potential prognostic factors survival surgery surveyed worldwide literature 1981 2018 obtained clinicopathological data 65 patients undergone surgical resection nec gallbladder relationships potential prognostic factors survival rates examined kaplan meier method log rank test 1 3 5 year disease specific survival rates surgery 70 2 39 3 29 5 respectively multivariate analysis revealed factors independently associated poor outcomes surgery patients nec gallbladder older age higher pathologic stage positive lymph node metastasis major sites recurrence liver lung lymph node local recurrence median time event recurrence 4 0 months even curative resection achieved 36 9 patients exhibited recurrence within 12 months curative resection gallbladder nec although nec gallbladder remains rare disease worldwide poor prognosis even curative resection demands epidemiological pathological studies lead development new management strategies pubmed","probabilities":0.9799733,"Title":"Clinicopathologic Features and Surgical Outcomes of Neuroendocrine Carcinoma of the Gallbladder","Abstract":"Neuroendocrine carcinoma (NEC) of the gallbladder is highly aggressive and has a poor prognosis even after curative resection. The purpose of this study was to collate and analyze published data to clarify the surgical outcome of NEC of the gallbladder and the relationships between potential prognostic factors and survival after surgery. We surveyed worldwide literature from 1981 to 2018 and obtained clinicopathological data for 65 patients who had undergone surgical resection for NEC of the gallbladder. The relationships between potential prognostic factors and survival rates were examined by the Kaplan-Meier method and the log-rank test. The 1-, 3-, and 5-year disease-specific survival rates after surgery were 70.2%, 39.3%, and 29.5%, respectively. A multivariate analysis revealed that the factors that were independently associated with poor outcomes after surgery in patients with NEC of the gallbladder were older age, higher pathologic T stage, and positive lymph node metastasis. The major sites of recurrence were the liver, lung, lymph node, and local recurrence. The median time to the event for recurrence was 4.0 months. Even when curative resection was achieved, 36.9% of patients exhibited recurrence within 12 months after curative resection of gallbladder NEC. Although NEC of the gallbladder remains a rare disease worldwide, its poor prognosis, even after curative resection, demands further epidemiological and pathological studies that could lead to the development of new management strategies.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathologic Features and Surgical Outcomes of Neuroendocrine Carcinoma of the Gallbladder Neuroendocrine carcinoma (NEC) of the gallbladder is highly aggressive and has a poor prognosis even after curative resection. The purpose of this study was to collate and analyze published data to clarify the surgical outcome of NEC of the gallbladder and the relationships between potential prognostic factors and survival after surgery. We surveyed worldwide literature from 1981 to 2018 and obtained clinicopathological data for 65 patients who had undergone surgical resection for NEC of the gallbladder. The relationships between potential prognostic factors and survival rates were examined by the Kaplan-Meier method and the log-rank test. The 1-, 3-, and 5-year disease-specific survival rates after surgery were 70.2%, 39.3%, and 29.5%, respectively. A multivariate analysis revealed that the factors that were independently associated with poor outcomes after surgery in patients with NEC of the gallbladder were older age, higher pathologic T stage, and positive lymph node metastasis. The major sites of recurrence were the liver, lung, lymph node, and local recurrence. The median time to the event for recurrence was 4.0 months. Even when curative resection was achieved, 36.9% of patients exhibited recurrence within 12 months after curative resection of gallbladder NEC. Although NEC of the gallbladder remains a rare disease worldwide, its poor prognosis, even after curative resection, demands further epidemiological and pathological studies that could lead to the development of new management strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"management incidental gallbladder cancer national cohort background incidental gallbladder cancer rare event prognosis largely affected tumour stage treatment aim study analyse management treatment survival patients incidental gallbladder cancer national cohort decade methods patients identified swedish registry gallstone surgery gallriks data cross linked national registry liver surgery sweliv cancer registry medical records collected registry data missing survival measured disease specific survival study divided two intervals 2007 2011 2012 2016 evaluate changes time results total 249 patients identified incidental gallbladder cancer 92 36 9 per cent underwent re resection curative intent patients pt2 pt3 disease median disease specific survival improved re resection 12 4 versus 44 1 months pt2 9 7 versus 23 0 months pt3 residual disease present 53 per cent patients pt2 tumours underwent re resection patients median disease specific survival 32 2 months whereas median reached patients without residual disease median survival increased 11 months patients early late periods p 0 030 conclusion re resection pt2 pt3 incidental gallbladder cancer associated improved survival survival impaired residual disease present higher re resection rate r0 resections later time period may associated improved survival pubmed","probabilities":0.9799733,"Title":"Management of incidental gallbladder cancer in a national cohort","Abstract":"BACKGROUND: Incidental gallbladder cancer is a rare event, and its prognosis is largely affected by the tumour stage and treatment. The aim of this study was to analyse the management, treatment and survival of patients with incidental gallbladder cancer in a national cohort over a decade. METHODS: Patients were identified through the Swedish Registry of Gallstone Surgery (GallRiks). Data were cross-linked to the national registry for liver surgery (SweLiv) and the Cancer Registry. Medical records were collected if registry data were missing. Survival was measured as disease-specific survival. The study was divided into two intervals (2007-2011 and 2012-2016) to evaluate changes over time. RESULTS: In total, 249 patients were identified with incidental gallbladder cancer, of whom 92 (36·9 per cent) underwent re-resection with curative intent. For patients with pT2 and pT3 disease, median disease-specific survival improved after re-resection (12·4 versus 44·1 months for pT2, and 9·7 versus 23·0 months for pT3). Residual disease was present in 53 per cent of patients with pT2 tumours who underwent re-resection; these patients had a median disease-specific survival of 32·2 months, whereas the median was not reached in patients without residual disease. Median survival increased by 11 months for all patients between the early and late periods (P = 0·030). CONCLUSION: Re-resection of pT2 and pT3 incidental gallbladder cancer was associated with improved survival, but survival was impaired when residual disease was present. A higher re-resection rate and more R0 resections in the later time period may have been associated with improved survival.","Source":"PubMed","category":"HUMAN","training_data":"Management of incidental gallbladder cancer in a national cohort BACKGROUND: Incidental gallbladder cancer is a rare event, and its prognosis is largely affected by the tumour stage and treatment. The aim of this study was to analyse the management, treatment and survival of patients with incidental gallbladder cancer in a national cohort over a decade. METHODS: Patients were identified through the Swedish Registry of Gallstone Surgery (GallRiks). Data were cross-linked to the national registry for liver surgery (SweLiv) and the Cancer Registry. Medical records were collected if registry data were missing. Survival was measured as disease-specific survival. The study was divided into two intervals (2007-2011 and 2012-2016) to evaluate changes over time. RESULTS: In total, 249 patients were identified with incidental gallbladder cancer, of whom 92 (36·9 per cent) underwent re-resection with curative intent. For patients with pT2 and pT3 disease, median disease-specific survival improved after re-resection (12·4 versus 44·1 months for pT2, and 9·7 versus 23·0 months for pT3). Residual disease was present in 53 per cent of patients with pT2 tumours who underwent re-resection; these patients had a median disease-specific survival of 32·2 months, whereas the median was not reached in patients without residual disease. Median survival increased by 11 months for all patients between the early and late periods (P = 0·030). CONCLUSION: Re-resection of pT2 and pT3 incidental gallbladder cancer was associated with improved survival, but survival was impaired when residual disease was present. A higher re-resection rate and more R0 resections in the later time period may have been associated with improved survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"significance s100p biomarker diagnosis prognosis therapy opisthorchiasis associated cholangiocarcinoma cholangiocarcinoma cca malignancy bile duct difficulty early diagnosis poor prognosis less alternation therapy s100p member s100 family proteins plays important roles cancers investigated s100p expression correlation clinicopathology 78 cases opisthorchiasis associated cca effects s100p knockdown shrna interference proliferation cell cycle migration apoptosis sensitivity anti cancer drug extremely high expression s100p mrna detected cca tumor tissues increased s100p protein expression immunohistochemically confirmed localized cca cytoplasm nuclei well hyperneoplasia dysplasia bile ducts normal bile ducts intensity immunostaining correlated survival tumor stage metastasis high expression independent prognostic factor high levels s100p detected serum bile fluid cca patients shrna mediated knockdown s100p expression inhibited proliferation vitro vivo migration cca cells arrested cell cycle regulated expression cell cycle arrest related factors p21 p27 gadd45a 14 3 3 zeta s100p knockdown also promoted cca cell apoptosis regulating expression apoptosis related factors dr5 tradd caspase 3 bax increased sensitivity cca cells chemotherapeutic agents sunitinib apigenin taken together study indicates s100p might promising biomarker diagnosis prognosis therapy cca stn","probabilities":0.9467213,"Title":"Significance Of S100P As A Biomarker In Diagnosis Prognosis And Therapy Of Opisthorchiasis-Associated Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a malignancy of bile duct with the difficulty in early diagnosis, poor prognosis and less alternation in therapy. S100P is a member of S100 family proteins and plays important roles in cancers. We investigated the S100P expression and its correlation with clinicopathology in 78 cases of opisthorchiasis-associated CCA, and the effects of S100P knockdown with shRNA interference on the proliferation, cell cycle, migration, apoptosis and sensitivity to anti-cancer drug. Extremely high expression of S100P mRNA was detected in the CCA tumor tissues. The increased S100P protein expression was immunohistochemically confirmed and localized in the CCA cytoplasm and/or nuclei as well as in the hyperneoplasia and dysplasia bile ducts, but not in normal bile ducts. The intensity of immunostaining was correlated with survival, tumor stage and metastasis, and the high expression could be an independent prognostic factor. High levels of S100P were detected in the serum and bile fluid of CCA patients. The shRNA-mediated knockdown of S100P expression inhibited the proliferation in vitro and in vivo, and migration of CCA cells, arrested cell cycle with the up-regulated expression of cell cycle arrest related factors, p21, p27, GADD45A, and 14-3-3 zeta. S100P knockdown also promoted CCA cell apoptosis by up-regulating expression of apoptosis related factors, DR5, TRADD, caspase 3 and BAX, and increased the sensitivity of CCA cells to the chemotherapeutic agents sunitinib and apigenin. Taken together, this study indicates that S100P might be a promising biomarker for the diagnosis, prognosis and therapy of CCA.","Source":"STN","category":"ANIMAL","training_data":"Significance Of S100P As A Biomarker In Diagnosis Prognosis And Therapy Of Opisthorchiasis-Associated Cholangiocarcinoma Cholangiocarcinoma (CCA) is a malignancy of bile duct with the difficulty in early diagnosis, poor prognosis and less alternation in therapy. S100P is a member of S100 family proteins and plays important roles in cancers. We investigated the S100P expression and its correlation with clinicopathology in 78 cases of opisthorchiasis-associated CCA, and the effects of S100P knockdown with shRNA interference on the proliferation, cell cycle, migration, apoptosis and sensitivity to anti-cancer drug. Extremely high expression of S100P mRNA was detected in the CCA tumor tissues. The increased S100P protein expression was immunohistochemically confirmed and localized in the CCA cytoplasm and/or nuclei as well as in the hyperneoplasia and dysplasia bile ducts, but not in normal bile ducts. The intensity of immunostaining was correlated with survival, tumor stage and metastasis, and the high expression could be an independent prognostic factor. High levels of S100P were detected in the serum and bile fluid of CCA patients. The shRNA-mediated knockdown of S100P expression inhibited the proliferation in vitro and in vivo, and migration of CCA cells, arrested cell cycle with the up-regulated expression of cell cycle arrest related factors, p21, p27, GADD45A, and 14-3-3 zeta. S100P knockdown also promoted CCA cell apoptosis by up-regulating expression of apoptosis related factors, DR5, TRADD, caspase 3 and BAX, and increased the sensitivity of CCA cells to the chemotherapeutic agents sunitinib and apigenin. Taken together, this study indicates that S100P might be a promising biomarker for the diagnosis, prognosis and therapy of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"radiotherapy still role unresected biliary tract cancer benefits radiotherapy inoperable biliary tract cancer remain unclear due lack randomized data evaluated impact radiotherapy survival elderly patients using seer medicare database patients seer medicare database inoperable biliary tract tumors diagnosed 1998 2011 included used multivariate logistic regression evaluate factors associated treatment selection multivariate cox regression propensity score matching evaluate treatment selection relation subsequent survival 2343 patients included 451 19 received radiotherapy within 4 months diagnosis use radiotherapy declined time influenced receipt chemotherapy patient age race marital status poverty status tumor stage type median survival 9 3 95 ci 8 7 9 7 months among patients receive radiation 10 0 95 ci 9 1 11 3 months among received radiation conditional survived 4 months patients received chemotherapy n 1053 receipt radiation associated improved survival adjusted hazard ratio 0 82 95 0 70 0 97 p 0 02 patients receive chemotherapy n 1290 receipt radiation associated improved survival adjusted hazard ratio 1 09 95 0 91 1 30 p 0 34 propensity scored matched analyses showed similar results despite survival benefit associated addition radiotherapy chemotherapy use radiation unresectable biliary tract cancers declined time pubmed","probabilities":0.9799733,"Title":"Does radiotherapy still have a role in unresected biliary tract cancer?","Abstract":"The benefits of radiotherapy for inoperable biliary tract cancer remain unclear due to the lack of randomized data. We evaluated the impact of radiotherapy on survival in elderly patients using the SEER-Medicare database. Patients in the SEER-Medicare database with inoperable biliary tract tumors diagnosed between 1998 and 2011 were included. We used multivariate logistic regression to evaluate factors associated with treatment selection, and multivariate Cox regression and propensity score matching to evaluate treatment selection in relation to subsequent survival. Of the 2343 patients included, 451 (19%) received radiotherapy within 4 months of diagnosis. The use of radiotherapy declined over time, and was influenced by receipt of chemotherapy and patient age, race, marital status, poverty status, and tumor stage and type. Median survival was 9.3 (95% CI 8.7-9.7) months among patients who did not receive radiation and 10.0 (95% CI 9.1-11.3) months among those who received radiation, conditional on having survived 4 months. In patients who received chemotherapy (n = 1053), receipt of radiation was associated with improved survival, with an adjusted hazard ratio of 0.82 (95% 0.70-0.97, P = 0.02). In patients who did not receive chemotherapy (n = 1290), receipt of radiation was not associated with improved survival, with an adjusted hazard ratio of 1.09 (95% 0.91-1.30, P = 0.34). Propensity-scored matched analyses showed similar results. Despite the survival benefit associated with the addition of radiotherapy to chemotherapy, the use of radiation for unresectable biliary tract cancers has declined over time.","Source":"PubMed","category":"HUMAN","training_data":"Does radiotherapy still have a role in unresected biliary tract cancer? The benefits of radiotherapy for inoperable biliary tract cancer remain unclear due to the lack of randomized data. We evaluated the impact of radiotherapy on survival in elderly patients using the SEER-Medicare database. Patients in the SEER-Medicare database with inoperable biliary tract tumors diagnosed between 1998 and 2011 were included. We used multivariate logistic regression to evaluate factors associated with treatment selection, and multivariate Cox regression and propensity score matching to evaluate treatment selection in relation to subsequent survival. Of the 2343 patients included, 451 (19%) received radiotherapy within 4 months of diagnosis. The use of radiotherapy declined over time, and was influenced by receipt of chemotherapy and patient age, race, marital status, poverty status, and tumor stage and type. Median survival was 9.3 (95% CI 8.7-9.7) months among patients who did not receive radiation and 10.0 (95% CI 9.1-11.3) months among those who received radiation, conditional on having survived 4 months. In patients who received chemotherapy (n = 1053), receipt of radiation was associated with improved survival, with an adjusted hazard ratio of 0.82 (95% 0.70-0.97, P = 0.02). In patients who did not receive chemotherapy (n = 1290), receipt of radiation was not associated with improved survival, with an adjusted hazard ratio of 1.09 (95% 0.91-1.30, P = 0.34). Propensity-scored matched analyses showed similar results. Despite the survival benefit associated with the addition of radiotherapy to chemotherapy, the use of radiation for unresectable biliary tract cancers has declined over time. PubMed","prediction_labels":"HUMAN"},{"cleaned":"evaluation cholangiocarcinoma risk related factors wetland geographical communities ubon ratchathani thailand wetland geographical areas higher incidence opisthorchis viverrini associated cholangiocarcinoma cca confirmed data geographic information systems areas behavioral data also indicate people areas traditionally eat uncooked freshwater fish dishes vehicle o viverrini infection best approach reducing cca incidence decreasing risk factors together behavior alteration evaluation cca risk related factors first needed planning prevention control programs future therefore aimed evaluate cca risk explore related factors among people wetland communities ubon ratchathani thailand cross sectional study conducted july august 2014 total 906 participants informed consent completed questionnaires overall risk cca determined multiplying odds ratios ors risk factors cca literature reviews mean score 5 95 applied cut point assessment factors related overall risk cca accomplished using conditional logistic regression participants 60 15 high level overall risk cca factors related overall risk cca gender 0 001 marital status 0 001 perceived susceptibility p 0 043 prevention behavior cca 0 001 conclusion participants community high level overall risk cca therefore integrated prevention control programs continue urgently required stn","probabilities":0.9799733,"Title":"Evaluation Of Cholangiocarcinoma Risk And Its Related Factors In Wetland Geographical Communities Of Ubon Ratchathani Thailand","Abstract":"Wetland geographical areas have a higher incidence of Opisthorchis viverrini-associated cholangiocarcinoma (CCA), confirmed by data from geographic information systems, than other areas. Behavioral data also indicate that people in these areas traditionally eat uncooked freshwater fish dishes, a vehicle for O. viverrini infection. The best approach to reducing CCA incidence is decreasing risk factors together with behavior alteration. Evaluation of CCA risk and its related factors are first needed for planning the prevention and control programs in the future. We therefore aimed to evaluate the CCA risk and explore its related factors among people in wetland communities of Ubon Ratchathani, Thailand. A cross-sectional study was conducted between July and August 2014. In total 906 participants, with informed consent, completed questionnaires. Overall risk of CCA was determined by multiplying odds ratios (ORs) of the risk factors for CCA from literature reviews. A mean score of 5.95 was applied as the cut-off point. Assessment of factors related to overall risk of CCA was accomplished using conditional logistic regression. Of all participants, 60.15% had a high level of the overall risk of CCA. Factors related to the overall risk of CCA were gender (<0.001), marital status (<0.001), perceived susceptibility (p=0.043) and prevention behavior for CCA (<0.001). In conclusion, most participants in this community had a high level of overall risk of CCA. Therefore, integrated prevention and control programs continue to be urgently required.","Source":"STN","category":"ANIMAL","training_data":"Evaluation Of Cholangiocarcinoma Risk And Its Related Factors In Wetland Geographical Communities Of Ubon Ratchathani Thailand Wetland geographical areas have a higher incidence of Opisthorchis viverrini-associated cholangiocarcinoma (CCA), confirmed by data from geographic information systems, than other areas. Behavioral data also indicate that people in these areas traditionally eat uncooked freshwater fish dishes, a vehicle for O. viverrini infection. The best approach to reducing CCA incidence is decreasing risk factors together with behavior alteration. Evaluation of CCA risk and its related factors are first needed for planning the prevention and control programs in the future. We therefore aimed to evaluate the CCA risk and explore its related factors among people in wetland communities of Ubon Ratchathani, Thailand. A cross-sectional study was conducted between July and August 2014. In total 906 participants, with informed consent, completed questionnaires. Overall risk of CCA was determined by multiplying odds ratios (ORs) of the risk factors for CCA from literature reviews. A mean score of 5.95 was applied as the cut-off point. Assessment of factors related to overall risk of CCA was accomplished using conditional logistic regression. Of all participants, 60.15% had a high level of the overall risk of CCA. Factors related to the overall risk of CCA were gender (<0.001), marital status (<0.001), perceived susceptibility (p=0.043) and prevention behavior for CCA (<0.001). In conclusion, most participants in this community had a high level of overall risk of CCA. Therefore, integrated prevention and control programs continue to be urgently required. STN","prediction_labels":"HUMAN"},{"cleaned":"chemoradiation therapy unresected extrahepatic cholangiocarcinoma propensity score matched analysis background unresected extrahepatic cholangiocarcinoma uehcc remains deadly disease guidelines uehcc recommend either chemotherapy alone ct chemoradiotherapy crt study used national cancer database ncdb compare outcomes patients treated ct underwent crt methods patients initially diagnosed non metastatic uehcc 2004 2014 identified using chi square analysis patients underwent ct compared received crt uni multivariate cox regression analyses used compare characteristics related survival propensity score matching shared frailty analysis undertaken correct baseline differences two groups additional analyses performed compare survival minority patients underwent surgery advanced stage patients results study identified 2996 patients uehcc chemoradiation associated better survival median survival ms 14 5 months hazard ratio hr 0 84 p 0 001 ct alone ms 12 6 months induction ct crt associated trend toward decreased risk death compared concurrent crt hr 0 81 p 0 051 patients able undergo surgery initial treatment ms 24 5 months hr 0 38 p 0 001 versus 12 2 months surgery patients crt also associated better survival ms 31 2 months hr 0 66 p 0 001 ct ms 22 1 months positive margins surgery yielded survival equivalent surgery conclusion although crt may associated slightly better survival uehcc ct alone majority benefit observed patients able undergo eventual surgery pubmed","probabilities":0.9799733,"Title":"Chemoradiation Therapy for Unresected Extrahepatic Cholangiocarcinoma: A Propensity Score-Matched Analysis","Abstract":"BACKGROUND: Unresected extrahepatic cholangiocarcinoma (uEHCC) remains a deadly disease. Guidelines for uEHCC recommend either chemotherapy alone (CT) or chemoradiotherapy (CRT). This study used the National Cancer Database (NCDB) to compare outcomes for patients treated with CT and those who underwent CRT. METHODS: Patients with initially diagnosed non-metastatic uEHCC from 2004 to 2014 were identified. Using Chi square analysis, patients who underwent CT were compared with those who received CRT. Uni- and multivariate Cox regression analyses were used to compare characteristics related to survival. Propensity score matching and shared frailty analysis were undertaken to correct for baseline differences between the two groups. Additional analyses were performed to compare survival for the minority of patients who underwent surgery and advanced-stage patients. RESULTS: The study identified 2996 patients with uEHCC. Chemoradiation was associated with better survival (median survival [MS], 14.5 months; hazard ratio [HR] 0.84; p < 0.001) than CT alone (MS, 12.6 months). Induction of CT before CRT was associated with a trend toward decreased risk of death compared with concurrent CRT (HR 0.81; p = 0.051). For the patients able to undergo surgery after initial treatment, MS was 24.5 months (HR 0.38; p < 0.001) versus 12.2 months for those who had no surgery. For these patients, CRT also was associated with better survival (MS, 31.2 months; HR 0.66; p = 0.001) than CT (MS, 22.1 months). Positive margins at surgery yielded survival equivalent to that with no surgery. CONCLUSION: Although CRT may be associated with slightly better survival in uEHCC than CT alone, the majority of the benefit was observed for patients able to undergo eventual surgery.","Source":"PubMed","category":"HUMAN","training_data":"Chemoradiation Therapy for Unresected Extrahepatic Cholangiocarcinoma: A Propensity Score-Matched Analysis BACKGROUND: Unresected extrahepatic cholangiocarcinoma (uEHCC) remains a deadly disease. Guidelines for uEHCC recommend either chemotherapy alone (CT) or chemoradiotherapy (CRT). This study used the National Cancer Database (NCDB) to compare outcomes for patients treated with CT and those who underwent CRT. METHODS: Patients with initially diagnosed non-metastatic uEHCC from 2004 to 2014 were identified. Using Chi square analysis, patients who underwent CT were compared with those who received CRT. Uni- and multivariate Cox regression analyses were used to compare characteristics related to survival. Propensity score matching and shared frailty analysis were undertaken to correct for baseline differences between the two groups. Additional analyses were performed to compare survival for the minority of patients who underwent surgery and advanced-stage patients. RESULTS: The study identified 2996 patients with uEHCC. Chemoradiation was associated with better survival (median survival [MS], 14.5 months; hazard ratio [HR] 0.84; p < 0.001) than CT alone (MS, 12.6 months). Induction of CT before CRT was associated with a trend toward decreased risk of death compared with concurrent CRT (HR 0.81; p = 0.051). For the patients able to undergo surgery after initial treatment, MS was 24.5 months (HR 0.38; p < 0.001) versus 12.2 months for those who had no surgery. For these patients, CRT also was associated with better survival (MS, 31.2 months; HR 0.66; p = 0.001) than CT (MS, 22.1 months). Positive margins at surgery yielded survival equivalent to that with no surgery. CONCLUSION: Although CRT may be associated with slightly better survival in uEHCC than CT alone, the majority of the benefit was observed for patients able to undergo eventual surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"perioperative transfusion real prognostic factor periampullary cancer following pancreatoduodenectomy purpose study clarify prognostic significance transfusion following pancreatoduodenectomy periampullary cancers analyzed 357 periampullary cancers 1985 1997 ampullary cancer 130 cases distal bile duct cancer 141 cases pancreatic head cancer 86 cases total 215 60 357 patients received intraoperative transfusion 5 year survival rate 130 ampullary cancer patients 59 altogether 76 patients 58 underwent intraoperative transfusion 5 year survival rate patients without intraoperative transfusion 79 whereas patients transfusion 47 p 0 029 following multivariate analysis intraoperative transfusion found independent poor prognostic factor ampullary cancer relative risk 2 174 among common bile duct cancer overall 5 year survival rate 33 5 year survival rates patients n 87 without n 54 transfusion 25 38 respectively reach statistical significance p 0 0717 pancreatic head cancer overall 5 year survival rate 16 survival difference transfused n 52 untransfused n 34 patients present study reason clear although intraoperative transfusion independent significant prognostic factor ampullary cancer careful dissection minimize intraoperative bleeding mandatory pancreatoduodenectomy ampullary cancer stn","probabilities":0.9799733,"Title":"Perioperative Transfusion: Is It A Real Prognostic Factor Of Periampullary Cancer Following Pancreatoduodenectomy?","Abstract":"The purpose of this study was to clarify the prognostic significance of transfusion following pancreatoduodenectomy for periampullary cancers. We analyzed 357 periampullary cancers from 1985 to 1997 (ampullary cancer 130 cases, distal bile duct cancer 141 cases, pancreatic head cancer 86 cases). A total of 215 (60%) of the 357 patients have received intraoperative transfusion. The 5-year survival rate of 130 ampullary cancer patients was 59%; altogether, 76 patients (58%) underwent intraoperative transfusion. The 5-year survival rate of patients without intraoperative transfusion was 79%, whereas that of patients with a transfusion was 47% (p = 0.029). Following multivariate analysis, intraoperative transfusion was found to be an independent poor prognostic factor for those with ampullary cancer (relative risk 2.174). Among those with common bile duct cancer, the overall 5-year survival rate was 33%, and the 5-year survival rates for patients with (n = 87) or without (n = 54) transfusion were 25% and 38%, respectively, which did not reach statistical significance (p = 0.0717). For those with pancreatic head cancer, the overall 5-year survival rate was 16%, and there was no survival difference between transfused (n = 52) and untransfused (n = 34) patients. In the present study the reason was not clear, although intraoperative transfusion was an independent significant prognostic factor for ampullary cancer. Careful dissection to minimize intraoperative bleeding is mandatory during pancreatoduodenectomy for ampullary cancer.","Source":"STN","category":"HUMAN","training_data":"Perioperative Transfusion: Is It A Real Prognostic Factor Of Periampullary Cancer Following Pancreatoduodenectomy? The purpose of this study was to clarify the prognostic significance of transfusion following pancreatoduodenectomy for periampullary cancers. We analyzed 357 periampullary cancers from 1985 to 1997 (ampullary cancer 130 cases, distal bile duct cancer 141 cases, pancreatic head cancer 86 cases). A total of 215 (60%) of the 357 patients have received intraoperative transfusion. The 5-year survival rate of 130 ampullary cancer patients was 59%; altogether, 76 patients (58%) underwent intraoperative transfusion. The 5-year survival rate of patients without intraoperative transfusion was 79%, whereas that of patients with a transfusion was 47% (p = 0.029). Following multivariate analysis, intraoperative transfusion was found to be an independent poor prognostic factor for those with ampullary cancer (relative risk 2.174). Among those with common bile duct cancer, the overall 5-year survival rate was 33%, and the 5-year survival rates for patients with (n = 87) or without (n = 54) transfusion were 25% and 38%, respectively, which did not reach statistical significance (p = 0.0717). For those with pancreatic head cancer, the overall 5-year survival rate was 16%, and there was no survival difference between transfused (n = 52) and untransfused (n = 34) patients. In the present study the reason was not clear, although intraoperative transfusion was an independent significant prognostic factor for ampullary cancer. Careful dissection to minimize intraoperative bleeding is mandatory during pancreatoduodenectomy for ampullary cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"significant increase incidence hepatocellular carcinoma wales introduction increasing mortality rates types primary liver cancer documented several coun tries recent years figures published england wales described marked increase mortality intrahepatic cholangiocarcinoma static declining rate hepatocellular carcinoma hcc khan sa et al 2002 however last decade prevalence several risk factors hcc chronic viral hepatitis alcoholic liver disease obesity nash dramatically increased wales therefore hypothesised due significant difference population size two regions dilutional effect may masked true incidence hcc within wales methods database welsh cancer intelligence surveillance unit examined liver tumour types affect ing welsh residents regardless treatment location across years 1999 2008 inclusive incidence recorded european age standardised rate easr per 100 000 pop ulation sub category analysis made hepatocellular car cinoma fibrolamellar hcc combined hcc cholangiocarcinoma liver malignant neoplasms patients stratified according age sex addi tional three year moving average easr calculated across whole study period results significant pro gressive increase incidence hcc wales 1999 2008 absolute numbers hcc cases easr proportion malignant liver neoplasms caused hcc risen men easr increased 100 8 years 1 9 3 8 per 100 000 addition easr increased women 83 0 6 1 1 per 100 000 rolling three year average rates closely followed trends throughout 10 year study period importantly detected significant rise proportion hcc cases affecting women age 75 years rising 47 75 last decade p 0 05 conclusion data reveals important differences previously published pooled figures england wales contrast studies found incidence hepatocellular carcinoma consistently increased last decade wales also documented significant rise hcc cases affecting younger women findings may reflect regional changes hcc risk factors may obscured combining figures much larger population england research necessary determine underlying causes increase improve prevention early detec tion hcc wales google scholar","probabilities":0.9799733,"Title":"Significant Increase In The Incidence Of Hepatocellular Carcinoma In Wales","Abstract":"INTRODUCTION: Increasing mortality rates for some types of\nprimary liver cancer have been documented in several coun-\ntries in recent years. The figures published for England and\nWales have described a marked increase in mortality from\nintrahepatic cholangiocarcinoma with a static or declining rate\nfor hepatocellular carcinoma (HCC) [Khan SA et al 2002].\nHowever, over the last decade, the prevalence of several risk\nfactors for HCC (chronic viral hepatitis, alcoholic liver disease\nand obesity/NASH) have all dramatically increased in Wales.\nWe therefore hypothesised that, due to the significant difference\nin population size between these two regions, a dilutional effect\nmay have masked the true incidence of HCC within Wales.\nMETHODS: The database of the Welsh Cancer Intelligence and\nSurveillance Unit was examined for all liver tumour types affect-\ning Welsh residents regardless of treatment location across the\nyears 1999 to 2008 inclusive. The incidence was recorded as\nthe European Age Standardised Rate (EASR) per 100,000 pop-\nulation. Sub-category analysis was made for hepatocellular car-\ncinoma, fibrolamellar HCC, combined HCC and cholangiocarcinoma and all liver malignant neoplasms.\nPatients were stratified according to age and sex and an addi-\ntional three year moving-average EASR calculated across the\nwhole study period. RESULTS: There was a significant and pro-\ngressive increase in the incidence of HCC in Wales from 1999\nto 2008. The absolute numbers of HCC cases, the EASR and\nthe proportion of malignant liver neoplasms caused by HCC\nhave all risen. In men, the EASR increased by 100% in just 8\nyears from 1.9 to 3.8 per 100,000. In addition, the EASR\nincreased in women by 83% from 0.6 to 1.1 per 100,000. The\nrolling three year average rates closely followed these trends\nthroughout the 10 year study period. Importantly, we detected\na significant rise in the proportion of HCC cases affecting\nwomen below the age of 75 years, rising from 47% to 75%\nover the last decade (p<0.05). CONCLUSION: Our data\nreveals important differences from the previously-published,\npooled figures for England and Wales. In contrast with these\nstudies, we found the incidence of hepatocellular carcinoma\nhas consistently increased over the last decade in Wales. We\nalso documented a significant rise in HCC cases affecting\nyounger women. These findings may reflect regional changes\nin HCC risk factors and may have been obscured by combining\nfigures with the much larger population of England. Further\nresearch will be necessary to determine the underlying causes\nof this increase and to improve the prevention and early detec-\ntion of HCC in Wales","Source":"Google Scholar","category":"HUMAN","training_data":"Significant Increase In The Incidence Of Hepatocellular Carcinoma In Wales INTRODUCTION: Increasing mortality rates for some types of\nprimary liver cancer have been documented in several coun-\ntries in recent years. The figures published for England and\nWales have described a marked increase in mortality from\nintrahepatic cholangiocarcinoma with a static or declining rate\nfor hepatocellular carcinoma (HCC) [Khan SA et al 2002].\nHowever, over the last decade, the prevalence of several risk\nfactors for HCC (chronic viral hepatitis, alcoholic liver disease\nand obesity/NASH) have all dramatically increased in Wales.\nWe therefore hypothesised that, due to the significant difference\nin population size between these two regions, a dilutional effect\nmay have masked the true incidence of HCC within Wales.\nMETHODS: The database of the Welsh Cancer Intelligence and\nSurveillance Unit was examined for all liver tumour types affect-\ning Welsh residents regardless of treatment location across the\nyears 1999 to 2008 inclusive. The incidence was recorded as\nthe European Age Standardised Rate (EASR) per 100,000 pop-\nulation. Sub-category analysis was made for hepatocellular car-\ncinoma, fibrolamellar HCC, combined HCC and cholangiocarcinoma and all liver malignant neoplasms.\nPatients were stratified according to age and sex and an addi-\ntional three year moving-average EASR calculated across the\nwhole study period. RESULTS: There was a significant and pro-\ngressive increase in the incidence of HCC in Wales from 1999\nto 2008. The absolute numbers of HCC cases, the EASR and\nthe proportion of malignant liver neoplasms caused by HCC\nhave all risen. In men, the EASR increased by 100% in just 8\nyears from 1.9 to 3.8 per 100,000. In addition, the EASR\nincreased in women by 83% from 0.6 to 1.1 per 100,000. The\nrolling three year average rates closely followed these trends\nthroughout the 10 year study period. Importantly, we detected\na significant rise in the proportion of HCC cases affecting\nwomen below the age of 75 years, rising from 47% to 75%\nover the last decade (p<0.05). CONCLUSION: Our data\nreveals important differences from the previously-published,\npooled figures for England and Wales. In contrast with these\nstudies, we found the incidence of hepatocellular carcinoma\nhas consistently increased over the last decade in Wales. We\nalso documented a significant rise in HCC cases affecting\nyounger women. These findings may reflect regional changes\nin HCC risk factors and may have been obscured by combining\nfigures with the much larger population of England. Further\nresearch will be necessary to determine the underlying causes\nof this increase and to improve the prevention and early detec-\ntion of HCC in Wales Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"development validation prognostic score intrahepatic cholangiocarcinoma importance patients intrahepatic cholangiocarcinoma icc oncologic benefit surgery perioperative outcomes large multifocal tumors tumors contiguous organ involvement remain defined objectives develop externally validate simplified prognostic score icc determine perioperative outcomes large multifocal iccs tumors contiguous organ involvement design setting participants study contemporary cohort merged data california cancer registry january 1 2004 december 31 2011 office statewide health planning development inpatient database clinicopathologic variables compared tumors intrahepatic small 7 cm solitary iss extrahepatic extension large 7 cm multifocal elm external validation prognostic model performed using independent data set national cancer institute surveillance epidemiology end results database january 1 2004 december 31 2013 main outcomes measures patient overall survival hepatectomy results total 275 patients 123 men 44 7 152 women 55 3 median interquartile range age 65 55 72 years met inclusion criteria significant differences overall complication rate iss 48 34 5 elm 37 27 2 p 19 mortality rate iss 10 7 2 elm 6 4 4 p 32 found multivariate cox proportional hazards model demonstrated multifocality extrahepatic extension grade node positivity age greater 60 years independently associated worse overall survival variables used develop megna prognostic score prognostic separation discrimination index improved megna prognostic score 0 21 95 ci 0 11 0 33 compared staging systems american joint committee cancer sixth 0 17 95 ci 0 09 0 29 seventh 0 18 95 ci 0 08 0 30 editions conclusions relevance megna prognostic score allows accurate superior estimation patient survival hepatectomy compared current staging systems pubmed","probabilities":0.9799733,"Title":"Development and Validation of a Prognostic Score for Intrahepatic Cholangiocarcinoma","Abstract":"IMPORTANCE: In patients with intrahepatic cholangiocarcinoma (ICC), the oncologic benefit of surgery and perioperative outcomes for large multifocal tumors or tumors with contiguous organ involvement remain to be defined. OBJECTIVES: To develop and externally validate a simplified prognostic score for ICC and to determine perioperative outcomes for large multifocal ICCs or tumors with contiguous organ involvement. DESIGN, SETTING, AND PARTICIPANTS: This study of a contemporary cohort merged data from the California Cancer Registry (January 1, 2004, through December 31, 2011) and the Office of Statewide Health Planning and Development inpatient database. Clinicopathologic variables were compared between tumors that were intrahepatic, small (<7 cm), and solitary (ISS) and those that had extrahepatic extension and were large (≥7 cm) and multifocal (ELM). External validation of the prognostic model was performed using an independent data set from the National Cancer Institute's Surveillance, Epidemiology, and End Results database from January 1, 2004, through December 31, 2013. MAIN OUTCOMES AND MEASURES: Patient overall survival after hepatectomy. RESULTS: A total of 275 patients (123 men [44.7%] and 152 women [55.3%]; median [interquartile range] age, 65 [55-72] years) met the inclusion criteria. No significant differences in overall complication rate (ISS, 48 [34.5%]; ELM, 37 [27.2%]; P = .19) and mortality rate (ISS, 10 [7.2%]; ELM, 6 [4.4%]; P = .32) were found. A multivariate Cox proportional hazards model demonstrated that multifocality, extrahepatic extension, grade, node positivity, and age greater than 60 years are independently associated with worse overall survival. These variables were used to develop the MEGNA prognostic score. The prognostic separation/discrimination index was improved with the MEGNA prognostic score (0.21; 95% CI, 0.11-0.33) compared with the staging systems of the American Joint Committee on Cancer sixth (0.17; 95% CI, 0.09-0.29) and seventh (0.18; 95% CI, 0.08-0.30) editions. CONCLUSIONS AND RELEVANCE: The MEGNA prognostic score allows more accurate and superior estimation of patient survival after hepatectomy compared with current staging systems.","Source":"PubMed","category":"HUMAN","training_data":"Development and Validation of a Prognostic Score for Intrahepatic Cholangiocarcinoma IMPORTANCE: In patients with intrahepatic cholangiocarcinoma (ICC), the oncologic benefit of surgery and perioperative outcomes for large multifocal tumors or tumors with contiguous organ involvement remain to be defined. OBJECTIVES: To develop and externally validate a simplified prognostic score for ICC and to determine perioperative outcomes for large multifocal ICCs or tumors with contiguous organ involvement. DESIGN, SETTING, AND PARTICIPANTS: This study of a contemporary cohort merged data from the California Cancer Registry (January 1, 2004, through December 31, 2011) and the Office of Statewide Health Planning and Development inpatient database. Clinicopathologic variables were compared between tumors that were intrahepatic, small (<7 cm), and solitary (ISS) and those that had extrahepatic extension and were large (≥7 cm) and multifocal (ELM). External validation of the prognostic model was performed using an independent data set from the National Cancer Institute's Surveillance, Epidemiology, and End Results database from January 1, 2004, through December 31, 2013. MAIN OUTCOMES AND MEASURES: Patient overall survival after hepatectomy. RESULTS: A total of 275 patients (123 men [44.7%] and 152 women [55.3%]; median [interquartile range] age, 65 [55-72] years) met the inclusion criteria. No significant differences in overall complication rate (ISS, 48 [34.5%]; ELM, 37 [27.2%]; P = .19) and mortality rate (ISS, 10 [7.2%]; ELM, 6 [4.4%]; P = .32) were found. A multivariate Cox proportional hazards model demonstrated that multifocality, extrahepatic extension, grade, node positivity, and age greater than 60 years are independently associated with worse overall survival. These variables were used to develop the MEGNA prognostic score. The prognostic separation/discrimination index was improved with the MEGNA prognostic score (0.21; 95% CI, 0.11-0.33) compared with the staging systems of the American Joint Committee on Cancer sixth (0.17; 95% CI, 0.09-0.29) and seventh (0.18; 95% CI, 0.08-0.30) editions. CONCLUSIONS AND RELEVANCE: The MEGNA prognostic score allows more accurate and superior estimation of patient survival after hepatectomy compared with current staging systems. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer decreasing view increasing laparoscopic cholecystectomy background gallstone disease affects 20 million people u major risk factor gallbladder cancer gbc 1988 less invasive low cost procedure laparoscopic cholecystectomy lc introduced became standard care management gallstones methods gbc incidence 1973 2007 mortality rates 1969 2006 calculated using seer program data lc rates 1993 2008 obtained namcs nhamcs hcup annual percent change estimated gender age race statistical significance assessed p 0 05 correlation analysis performed gbc lc trends results since early 1970s gbc incidence mortality rate declined women older age groups continue highest risk gbc despite greater declines incidence significantly decreased among whites among blacks number inpatient lc procedures increased 15 1994 2008 however inpatient outpatient lc rates remained stable lc rate significantly correlated either gbc incidence mortality conclusions decline incidence mortality gbc began decades introduction lc apparently stabilized past decade temporal relationship existed lc rate incidence mortality rates gbc study suggests prevention rare tumor may extremely difficult surgical removal risk factor involved pubmed","probabilities":0.9799733,"Title":"Is gallbladder cancer decreasing in view of increasing laparoscopic cholecystectomy?","Abstract":"BACKGROUND: Gallstone disease affects over 20 million people in the U.S. and is a major risk factor for gallbladder cancer (GBC). In 1988, a less invasive, low-cost procedure, laparoscopic cholecystectomy (LC), was introduced and became the standard of care for management of gallstones. METHODS: GBC incidence (1973-2007) and mortality rates (1969-2006) were calculated using SEER Program data. LC rates (1993-2008) were obtained from NAMCS, NHAMCS, and HCUP. Annual percent change was estimated by gender, age, and race, and the statistical significance was assessed at p < 0.05. Correlation analysis was performed on GBC and LC trends. RESULTS: Since the early 1970s, GBC incidence and mortality rate have declined. Women and older age groups continue to have the highest risk for GBC, despite having greater declines. Incidence significantly decreased among whites, but did not among blacks. The number of inpatient LC procedures increased by 15% between 1994 and 2008; however, inpatient and outpatient LC rates remained stable. LC rate was not significantly correlated with either GBC incidence or mortality. CONCLUSIONS: The decline in incidence and mortality of GBC began decades before the introduction of LC and apparently has stabilized in the past decade. No temporal relationship existed between LC rate and the incidence and mortality rates of GBC. Our study suggests that prevention of a rare tumor may be extremely difficult if the surgical removal of a risk factor is involved.","Source":"PubMed","category":"HUMAN","training_data":"Is gallbladder cancer decreasing in view of increasing laparoscopic cholecystectomy? BACKGROUND: Gallstone disease affects over 20 million people in the U.S. and is a major risk factor for gallbladder cancer (GBC). In 1988, a less invasive, low-cost procedure, laparoscopic cholecystectomy (LC), was introduced and became the standard of care for management of gallstones. METHODS: GBC incidence (1973-2007) and mortality rates (1969-2006) were calculated using SEER Program data. LC rates (1993-2008) were obtained from NAMCS, NHAMCS, and HCUP. Annual percent change was estimated by gender, age, and race, and the statistical significance was assessed at p < 0.05. Correlation analysis was performed on GBC and LC trends. RESULTS: Since the early 1970s, GBC incidence and mortality rate have declined. Women and older age groups continue to have the highest risk for GBC, despite having greater declines. Incidence significantly decreased among whites, but did not among blacks. The number of inpatient LC procedures increased by 15% between 1994 and 2008; however, inpatient and outpatient LC rates remained stable. LC rate was not significantly correlated with either GBC incidence or mortality. CONCLUSIONS: The decline in incidence and mortality of GBC began decades before the introduction of LC and apparently has stabilized in the past decade. No temporal relationship existed between LC rate and the incidence and mortality rates of GBC. Our study suggests that prevention of a rare tumor may be extremely difficult if the surgical removal of a risk factor is involved. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors scoring model survival advanced biliary tract cancer background metastatic biliary tract cancer btc dismal prognosis herein presented multivariate analysis using routinely evaluated clinico laboratory parameters time initial diagnosis implement scoring model effectively identify risk groups finally validated model using independent dataset methods september 2006 february 2015 482 patients metastatic btc analyzed patients randomly assigned 7 3 investigational n 340 validation dataset n 142 continuous variables dichotomized according normal range best cutoff values statistically determined contal o quigley method multivariate analysis using cox proportional hazard model done find independent prognostic factors scoring model derived summing rounded 2 scores factors emerged multivariate analysis results performance status ecog 3 4 hypoalbuminemia 3 4 mg dl carcinoembryonic antigen 9 ng ml neutrophil lymphocyte ratio 3 0 carbohydrate antigen 19 9 120 u ml identified independent factors poor survival investigational dataset assigning patients three risk groups based factors survival 14 0 7 3 2 3 months low intermediate high risk groups respectively p 0 001 harrell c index integrated auc scoring model 0 682 0 653 respectively validation dataset prognosis also well divided according risk groups median os 16 7 7 5 1 9 months respectively p 0 001 chemotherapy gave survival benefit low intermediate risk group 11 4 vs 4 8 months p 0 001 high risk group median os 4 3 vs 1 1 months p 0 105 conclusions propose set prognostic criteria metastatic btc help accurate patient risk stratification aid treatment selection google scholar","probabilities":0.9799733,"Title":"Prognostic Factors And Scoring Model For Survival In Advanced Biliary Tract Cancer","Abstract":"Background: Metastatic biliary tract cancer (BTC) has dismal prognosis. We herein presented multivariate analysis using routinely evaluated clinico-laboratory parameters at the time of initial diagnosis, to implement a scoring model that can effectively identify risk groups, and we finally validated the model using independent dataset. Methods: From September 2006 to February 2015, 482 patients with metastatic BTC were analyzed. Patients were randomly assigned (7:3) into investigational (n = 340) and validation dataset (n = 142). Continuous variables were dichotomized according to the normal range or the best cutoff values statistically determined by Contal and O’Quigley method. Multivariate analysis using Cox’s proportional hazard model was done to find independent prognostic factors, and scoring model were derived by summing the rounded χ2 scores for the factors emerged in the multivariate analysis. Results: Performance status (ECOG 3-4), hypoalbuminemia ( < 3.4 mg/dL), carcinoembryonic antigen (≥9 ng/mL), neutrophil-lymphocyte ratio (≥3.0), and carbohydrate antigen 19-9 (≥120 U/mL) were identified as independent factors for poor survival in investigational dataset. When assigning patients into three risk groups based on these factors, survival was 14.0, 7.3, and 2.3 months for the low, intermediate, and high-risk groups, respectively (P < 0.001). Harrell’s C-index and integrated AUC for scoring model were 0.682 and 0.653, respectively. In validation dataset, prognosis was also well-divided according to the risk groups (median OS, 16.7, 7.5 and 1.9 months, respectively, P < 0.001). Chemotherapy gave a survival benefit in low and intermediate-risk group (11.4 vs. 4.8 months; P< 0.001), but not in high-risk group (median OS, 4.3 vs. 1.1 months; P = 0.105). Conclusions: We propose a set of prognostic criteria for metastatic BTC, which can help accurate patient risk stratification and aid in treatment selection.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Factors And Scoring Model For Survival In Advanced Biliary Tract Cancer Background: Metastatic biliary tract cancer (BTC) has dismal prognosis. We herein presented multivariate analysis using routinely evaluated clinico-laboratory parameters at the time of initial diagnosis, to implement a scoring model that can effectively identify risk groups, and we finally validated the model using independent dataset. Methods: From September 2006 to February 2015, 482 patients with metastatic BTC were analyzed. Patients were randomly assigned (7:3) into investigational (n = 340) and validation dataset (n = 142). Continuous variables were dichotomized according to the normal range or the best cutoff values statistically determined by Contal and O’Quigley method. Multivariate analysis using Cox’s proportional hazard model was done to find independent prognostic factors, and scoring model were derived by summing the rounded χ2 scores for the factors emerged in the multivariate analysis. Results: Performance status (ECOG 3-4), hypoalbuminemia ( < 3.4 mg/dL), carcinoembryonic antigen (≥9 ng/mL), neutrophil-lymphocyte ratio (≥3.0), and carbohydrate antigen 19-9 (≥120 U/mL) were identified as independent factors for poor survival in investigational dataset. When assigning patients into three risk groups based on these factors, survival was 14.0, 7.3, and 2.3 months for the low, intermediate, and high-risk groups, respectively (P < 0.001). Harrell’s C-index and integrated AUC for scoring model were 0.682 and 0.653, respectively. In validation dataset, prognosis was also well-divided according to the risk groups (median OS, 16.7, 7.5 and 1.9 months, respectively, P < 0.001). Chemotherapy gave a survival benefit in low and intermediate-risk group (11.4 vs. 4.8 months; P< 0.001), but not in high-risk group (median OS, 4.3 vs. 1.1 months; P = 0.105). Conclusions: We propose a set of prognostic criteria for metastatic BTC, which can help accurate patient risk stratification and aid in treatment selection. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"increase mal ii binding alpha23 sialylated glycan associated 5 fu resistance short survival cholangiocarcinoma patients background objectives sialylation plays important roles tumor progression present study aimed demonstrate alteration sialylation role cholangiocarcinoma cca materials methods 2 3 2 6 sialylation cca tissue analyzed lectin histochemistry using maackia amurensis lectin ii mal ii sambucus nigra agglutinin sna cca cell lines treated pan sialylation inhibitor 3fax peracetyl neu5ac 3f sia followed proliferation chemosensitivity assays results mal ii binding 2 3 sialylated glycan mal sg sna binding 2 6 sialylated glycan sna sg elevated cca compared hyperplastic dysplastic hp dp normal bile ducts nbd positive staining mal sg sna sg found 82 61 74 cca cases higher expression mal sg cca associated shorter survival patients median survival patients high low mal sg 167 308 days respectively overall survival 233 days suggesting involvement mal sg cca progression mal sg expression cca cell lines markedly decreased treatment 3f sia 48 72 h proliferation cca cells affected 3f sia treatment susceptibility 5 fluorouracil 5 fu significantly enhanced results suggest sialylation involved development 5 fu resistance sialylation inhibitor 3f sia used chemosensitizer cca conclusions sialylation critically involved development chemoresistance cca sialylation inhibitors may used chemosensitizer cca treatment stn","probabilities":0.9467213,"Title":"Increase Of Mal-Ii Binding Alpha23-Sialylated Glycan Is Associated With 5-Fu Resistance And Short Survival Of Cholangiocarcinoma Patients","Abstract":"Background and objectives: Sialylation plays important roles in tumor progression. Our present study aimed to demonstrate the alteration of sialylation and its role in cholangiocarcinoma (CCA). \r\n\r\n Materials and methods: The α2,3- and α2,6-sialylation in CCA tissue was analyzed by lectin-histochemistry using Maackia amurensis lectin-II (MAL-II) and Sambucus nigra agglutinin (SNA). CCA cell lines were treated with the pan-sialylation inhibitor 3Fax-peracetyl-Neu5Ac (3F-Sia) followed by proliferation and chemosensitivity assays. \r\n\r\n Results: MAL-II binding α2,3-Sialylated Glycan (MAL-SG) and SNA binding α2,6-Sialylated Glycan (SNA-SG) were both elevated in CCA compared with hyperplastic/dysplastic (HP/DP) and normal bile ducts (NBD). The positive staining for MAL-SG or SNA-SG were found in 82% (61/74) of the CCA cases. Higher expression of MAL-SG in CCA was associated with shorter survival of the patients. The median survival of patients with high and low MAL-SG were 167 and 308 days, respectively, with overall survival of 233 days, suggesting the involvement of MAL-SG in CCA progression. MAL-SG expression of CCA cell lines was markedly decreased after treatment with 3F-Sia for 48 to 72 h. While proliferation of CCA cells were not affected by 3F-Sia treatment, their susceptibility to 5-fluorouracil (5-FU) was significantly enhanced. These results suggest that sialylation is involved in the development of 5-FU resistance and the sialylation inhibitor 3F-Sia can be used as a chemosensitizer for CCA. \r\n\r\n Conclusions: Sialylation is critically involved in the development of chemoresistance of CCA, and sialylation inhibitors may be used as a chemosensitizer in CCA treatment.","Source":"STN","category":"ANIMAL","training_data":"Increase Of Mal-Ii Binding Alpha23-Sialylated Glycan Is Associated With 5-Fu Resistance And Short Survival Of Cholangiocarcinoma Patients Background and objectives: Sialylation plays important roles in tumor progression. Our present study aimed to demonstrate the alteration of sialylation and its role in cholangiocarcinoma (CCA). \r\n\r\n Materials and methods: The α2,3- and α2,6-sialylation in CCA tissue was analyzed by lectin-histochemistry using Maackia amurensis lectin-II (MAL-II) and Sambucus nigra agglutinin (SNA). CCA cell lines were treated with the pan-sialylation inhibitor 3Fax-peracetyl-Neu5Ac (3F-Sia) followed by proliferation and chemosensitivity assays. \r\n\r\n Results: MAL-II binding α2,3-Sialylated Glycan (MAL-SG) and SNA binding α2,6-Sialylated Glycan (SNA-SG) were both elevated in CCA compared with hyperplastic/dysplastic (HP/DP) and normal bile ducts (NBD). The positive staining for MAL-SG or SNA-SG were found in 82% (61/74) of the CCA cases. Higher expression of MAL-SG in CCA was associated with shorter survival of the patients. The median survival of patients with high and low MAL-SG were 167 and 308 days, respectively, with overall survival of 233 days, suggesting the involvement of MAL-SG in CCA progression. MAL-SG expression of CCA cell lines was markedly decreased after treatment with 3F-Sia for 48 to 72 h. While proliferation of CCA cells were not affected by 3F-Sia treatment, their susceptibility to 5-fluorouracil (5-FU) was significantly enhanced. These results suggest that sialylation is involved in the development of 5-FU resistance and the sialylation inhibitor 3F-Sia can be used as a chemosensitizer for CCA. \r\n\r\n Conclusions: Sialylation is critically involved in the development of chemoresistance of CCA, and sialylation inhibitors may be used as a chemosensitizer in CCA treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"proposal modify international union cancer staging system perihilar cholangiocarcinomas background international union cancer uicc staging system perihilar cholangiocarcinoma changed 2009 aim study validate optimize uicc system tumours methods retrospective study conducted eight japanese hospitals 2001 2010 perihilar cholangiocarcinoma defined cholangiocarcinoma involves hilar bile duct independent presence absence liver mass component stratification ability uicc tumour node metastasis tnm system compared modified system results 1352 patients 35 9 44 8 12 6 per cent bismuth type iv tumours nodal metastasis n1 distant metastasis m1 respectively t4 tumours 43 2 per cent stage iva t4 nany m0 36 3 per cent disease common survival significantly different patients t3 versus t4 tumours p 0 284 survival patients stage iva disease comparable patients stage iiib tumours t1 3 n1 m0 p 0 426 vascular invasion pancreatic invasion positive margin n1 m1 status identified independent predictors survival bismuth type iv tumours removed t4 determinants n1 tumours grouped together modified grouping higher linear trend 2 likelihood ratio 2 compared original system 245 6 versus 170 3 respectively 255 8 versus 209 3 respectively conclusion present data suggest minimal modification removal bismuth type iv tumours t4 determinants bundling n1 disease may enhance prognostic ability uicc system however requires validation independent data set pubmed","probabilities":0.9799733,"Title":"Proposal to modify the International Union Against Cancer staging system for perihilar cholangiocarcinomas","Abstract":"BACKGROUND: The International Union Against Cancer (UICC) staging system for perihilar cholangiocarcinoma changed in 2009. The aim of this study was to validate and optimize the UICC system for these tumours. METHODS: This retrospective study was conducted in eight Japanese hospitals between 2001 and 2010. Perihilar cholangiocarcinoma was defined as a cholangiocarcinoma that involves the hilar bile duct, independent of the presence or absence of a liver mass component. The stratification ability of the UICC tumour node metastasis (TNM) system was compared with that of a modified system. RESULTS: Of 1352 patients, 35.9, 44.8 and 12.6 per cent had Bismuth type IV tumours, nodal metastasis (N1) and distant metastasis (M1) respectively. T4 tumours (43.2 per cent) and stage IVA (T4 Nany M0; 36.3 per cent) disease were most common. Survival was not significantly different between patients with T3 versus T4 tumours (P = 0.284). Survival for patients with stage IVA disease was comparable to that for patients with stage IIIB tumours (T1-3 N1 M0) (P = 0.426). Vascular invasion, pancreatic invasion, positive margin, N1 and M1 status were identified as independent predictors of survival. When Bismuth type IV tumours were removed from the T4 determinants and N1 tumours grouped together, the modified grouping had a higher linear trend χ2 and likelihood ratio χ2 compared with the original system (245.6 versus 170.3 respectively and 255.8 versus 209.3 respectively). CONCLUSION: The present data suggest that minimal modification with removal of Bismuth type IV tumours from the T4 determinants and bundling of N1 disease may enhance the prognostic ability of the UICC system. However, this requires validation on an independent data set.","Source":"PubMed","category":"HUMAN","training_data":"Proposal to modify the International Union Against Cancer staging system for perihilar cholangiocarcinomas BACKGROUND: The International Union Against Cancer (UICC) staging system for perihilar cholangiocarcinoma changed in 2009. The aim of this study was to validate and optimize the UICC system for these tumours. METHODS: This retrospective study was conducted in eight Japanese hospitals between 2001 and 2010. Perihilar cholangiocarcinoma was defined as a cholangiocarcinoma that involves the hilar bile duct, independent of the presence or absence of a liver mass component. The stratification ability of the UICC tumour node metastasis (TNM) system was compared with that of a modified system. RESULTS: Of 1352 patients, 35.9, 44.8 and 12.6 per cent had Bismuth type IV tumours, nodal metastasis (N1) and distant metastasis (M1) respectively. T4 tumours (43.2 per cent) and stage IVA (T4 Nany M0; 36.3 per cent) disease were most common. Survival was not significantly different between patients with T3 versus T4 tumours (P = 0.284). Survival for patients with stage IVA disease was comparable to that for patients with stage IIIB tumours (T1-3 N1 M0) (P = 0.426). Vascular invasion, pancreatic invasion, positive margin, N1 and M1 status were identified as independent predictors of survival. When Bismuth type IV tumours were removed from the T4 determinants and N1 tumours grouped together, the modified grouping had a higher linear trend χ2 and likelihood ratio χ2 compared with the original system (245.6 versus 170.3 respectively and 255.8 versus 209.3 respectively). CONCLUSION: The present data suggest that minimal modification with removal of Bismuth type IV tumours from the T4 determinants and bundling of N1 disease may enhance the prognostic ability of the UICC system. However, this requires validation on an independent data set. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association aspirin use biliary tract cancer survival database study analyzes association aspirin use survival patients biliary tract cancer stn","probabilities":0.9799733,"Title":"Association Between Aspirin Use And Biliary Tract Cancer Survival","Abstract":"This database study analyzes the association between aspirin use and survival in patients with biliary tract cancer.","Source":"STN","category":"HUMAN","training_data":"Association Between Aspirin Use And Biliary Tract Cancer Survival This database study analyzes the association between aspirin use and survival in patients with biliary tract cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"relationship enteric fever gallbladder cancer systematic review meta analysis background carcinoma gallbladder fth commonest gastro intestinal tract cancer endemic several countries association chronic typhoid carriage carcinoma gallbladder reported aim clarify whether chronic salmonella typhi carrier state associated carcinoma gallbladder methods systematic search conducted using medline pubmed embase current contents connect cochrane library google scholar science direct web science original data abstracted study used calculate pooled event rate er odd ratio 95 con dence interval 95 ci results studies south asia subgroup analysis performed according region signi cant association observed south east asia 4 13 95 ci 2 87 5 94 based study design performed subgroup analysis summary cohort studies 19 48 95 ci 0 27 1418 18 hand case control studies 3 08 95 ci 1 67 5 71 however overall 4 28 95 ci 1 84 9 96 chronic salmonella typhi carrier state associated carcinoma gallbladder based detection methods salmonella typhi antibody levels 3 52 95 ci 2 48 5 00 even culture 4 14 95 ci 2 41 7 12 hand past medical history typhoid related carcinoma gallbladder 3 33 95 ci 0 77 14 38 association prominent healthy controls 5 86 95 ci 3 84 8 95 compared controls gallstones 2 71 95 ci 1 92 3 83 conclusions chronic typhoid carrier state important risk factor among patients carcinoma gallbladder google scholar","probabilities":0.9799733,"Title":"Relationship Between Enteric Fever And Gallbladder Cancer: A Systematic Review And Meta-Analysis","Abstract":"Background: Carcinoma of the gallbladder is the fifth commonest gastro-\nintestinal tract cancer and is endemic in several countries. An association of\nchronic typhoid carriage and carcinoma of the gallbladder has been\nreported.\nAim: To clarify whether chronic Salmonella typhi carrier state is associated\nwith carcinoma of the gallbladder.\nMethods: A systematic search was conducted using MEDLINE, PubMed,\nEMBASE, Current Contents Connect, Cochrane library, Google Scholar,\nScience Direct, and Web of Science. Original data were abstracted from each\nstudy and used to calculate a pooled event rate (ER), odd ratio (OR) and\n95% confidence interval (95% CI) Results: Most of the studies were from South Asia. When a subgroup\nanalysis was performed according to region, a significant association was\nobserved in South East Asia (OR: 4.13, 95% CI: 2.87–5.94). Based on study\ndesign we performed a subgroup analysis. The summary OR for cohort studies was 19.48 (95% CI: 0.27–1418.18) on the other hand for the case\ncontrol studies the OR was 3.08 (95% CI: 1.67–5.71). However, the overall\nOR was 4.28(95% CI: 1.84–9.96).\nChronic Salmonella typhi carrier state was associated with carcinoma of the\ngallbladder based on detection methods of Salmonella typhi by antibody\nlevels (OR: 3.52, 95% CI: 2.48–5.00) and even more so on culture (OR:\n4.14, 95% CI: 2.41–7.12). On the other hand, a past medical history of\ntyphoid was not related with carcinoma of the gallbladder (OR: 3.33, 95%\nCI: 0.77–14.38). The association was prominent in healthy controls (OR:\n5.86, 95% CI: 3.84–8.95) when compared to controls with gallstones (OR:\n2.71, 95% CI: 1.92–3.83).\nConclusions: Chronic typhoid carrier state is an important risk factor\namong patients with carcinoma of the gallbladder.","Source":"Google Scholar","category":"HUMAN","training_data":"Relationship Between Enteric Fever And Gallbladder Cancer: A Systematic Review And Meta-Analysis Background: Carcinoma of the gallbladder is the fifth commonest gastro-\nintestinal tract cancer and is endemic in several countries. An association of\nchronic typhoid carriage and carcinoma of the gallbladder has been\nreported.\nAim: To clarify whether chronic Salmonella typhi carrier state is associated\nwith carcinoma of the gallbladder.\nMethods: A systematic search was conducted using MEDLINE, PubMed,\nEMBASE, Current Contents Connect, Cochrane library, Google Scholar,\nScience Direct, and Web of Science. Original data were abstracted from each\nstudy and used to calculate a pooled event rate (ER), odd ratio (OR) and\n95% confidence interval (95% CI) Results: Most of the studies were from South Asia. When a subgroup\nanalysis was performed according to region, a significant association was\nobserved in South East Asia (OR: 4.13, 95% CI: 2.87–5.94). Based on study\ndesign we performed a subgroup analysis. The summary OR for cohort studies was 19.48 (95% CI: 0.27–1418.18) on the other hand for the case\ncontrol studies the OR was 3.08 (95% CI: 1.67–5.71). However, the overall\nOR was 4.28(95% CI: 1.84–9.96).\nChronic Salmonella typhi carrier state was associated with carcinoma of the\ngallbladder based on detection methods of Salmonella typhi by antibody\nlevels (OR: 3.52, 95% CI: 2.48–5.00) and even more so on culture (OR:\n4.14, 95% CI: 2.41–7.12). On the other hand, a past medical history of\ntyphoid was not related with carcinoma of the gallbladder (OR: 3.33, 95%\nCI: 0.77–14.38). The association was prominent in healthy controls (OR:\n5.86, 95% CI: 3.84–8.95) when compared to controls with gallstones (OR:\n2.71, 95% CI: 1.92–3.83).\nConclusions: Chronic typhoid carrier state is an important risk factor\namong patients with carcinoma of the gallbladder. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"flotillin 2 predicts poor prognosis promotes tumor invasion intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icca highly malignant neoplasm arising intrahepatic bile ducts scaffold protein lipid rafts flotillin 2 upregulated several types cancer promotes tumor progression metastasis best knowledge present study first detect upregulation flotillin 2 icca tissues compared matched adjacent non tumor tissues addition immunohistochemistry used investigate expression flotillin 2 microarray consisting 92 icca tissues total 59 samples 64 1 exhibited high flotillin 2 expression significantly related lymph node metastasis p 0 029 tumor node metastasis stage p 0 016 vitro study demonstrated knockdown flotillin 2 inhibited invasive capability icca cell lines supporting participation flotillin 2 cancer invasion metastasis moreover kaplan meier analysis showed patients high flotillin 2 expression worse overall survival outcomes multivariate cox proportional hazards model revealed high flotillin 2 expression independent indicator p 0 005 poor prognosis patients icca collectively present study revealed promoter invasion independent marker poor prognosis flotillin 2 may serve potential target development novel therapeutic agents icca stn","probabilities":0.9467213,"Title":"Flotillin-2 Predicts Poor Prognosis And Promotes Tumor Invasion In Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant neoplasm arising from the intrahepatic bile ducts. As a scaffold protein of lipid rafts, flotillin-2 is upregulated in several types of cancer and promotes tumor progression and metastasis. To the best of our knowledge, the present study was the first to detect the upregulation of flotillin-2 in iCCA tissues compared with matched adjacent non-tumor tissues. In addition, immunohistochemistry was used to investigate the expression of flotillin-2 in a microarray consisting of 92 iCCA tissues. A total of 59 samples (64.1%) exhibited high flotillin-2 expression, which was significantly related to lymph node metastasis (P=0.029) and tumor-node-metastasis stage (P=0.016). Further in vitro study demonstrated that knockdown of flotillin-2 inhibited the invasive capability of iCCA cell lines, further supporting the participation of flotillin-2 in cancer invasion and metastasis. Moreover, Kaplan-Meier analysis showed patients with high flotillin-2 expression had worse overall survival outcomes. The multivariate Cox proportional hazards model further revealed that high flotillin-2 expression was an independent indicator (P=0.005) of poor prognosis for patients with iCCA. Collectively, the present study revealed that as a promoter of invasion and an independent marker of poor prognosis, flotillin-2 may serve as a potential target for the development of novel therapeutic agents for iCCA.","Source":"STN","category":"ANIMAL","training_data":"Flotillin-2 Predicts Poor Prognosis And Promotes Tumor Invasion In Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma (iCCA) is a highly malignant neoplasm arising from the intrahepatic bile ducts. As a scaffold protein of lipid rafts, flotillin-2 is upregulated in several types of cancer and promotes tumor progression and metastasis. To the best of our knowledge, the present study was the first to detect the upregulation of flotillin-2 in iCCA tissues compared with matched adjacent non-tumor tissues. In addition, immunohistochemistry was used to investigate the expression of flotillin-2 in a microarray consisting of 92 iCCA tissues. A total of 59 samples (64.1%) exhibited high flotillin-2 expression, which was significantly related to lymph node metastasis (P=0.029) and tumor-node-metastasis stage (P=0.016). Further in vitro study demonstrated that knockdown of flotillin-2 inhibited the invasive capability of iCCA cell lines, further supporting the participation of flotillin-2 in cancer invasion and metastasis. Moreover, Kaplan-Meier analysis showed patients with high flotillin-2 expression had worse overall survival outcomes. The multivariate Cox proportional hazards model further revealed that high flotillin-2 expression was an independent indicator (P=0.005) of poor prognosis for patients with iCCA. Collectively, the present study revealed that as a promoter of invasion and an independent marker of poor prognosis, flotillin-2 may serve as a potential target for the development of novel therapeutic agents for iCCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"lymph node micrometastases associated worse survival patients otherwise node negative hilar cholangiocarcinoma background lymph node metastases routine histology strong negative predictor survival resection hilar cholangiocarcinoma additional immunohistochemistry detect lymph node micrometastases patients otherwise node negative prognostic value unsure objective study assess effect survival immunohistochemically detected lymph node micrometastases patients node negative pn0 hilar cholangiocarcinoma routine histology methods 1990 2010 total 146 patients underwent curative intent resection hilar cholangiocarcinoma regional lymphadenectomy two university medical centers netherlands ninety one patients 62 without lymph node metastases routine histology included micrometastases identified multiple sectioning lymph nodes additional immunostaining antibody cytokeratin 19 k19 association overall survival assessed univariable multivariable analysis median follow 48 months results micrometastases identified 16 5 324 lymph nodes corresponding 11 12 91 patients differences clinical variables k19 lymph node positive negative patients five year survival rates patients lymph node micrometastases significantly lower compared patients without micrometastases 27 vs 54 p 0 01 multivariable analysis confirmed micrometastases independent prognostic factor survival adjusted hazard ratio 2 4 p 0 02 conclusions lymph node micrometastases associated worse survival resection hilar cholangiocarcinoma immunohistochemical detection lymph node micrometastases leads better staging patients initially diagnosed node negative pn0 hilar cholangiocarcinoma routine histology pubmed","probabilities":0.9799733,"Title":"Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma","Abstract":"BACKGROUND: Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of this study was to assess the effect on survival of immunohistochemically detected lymph node micrometastases in patients with node-negative (pN0) hilar cholangiocarcinoma on routine histology. METHODS: Between 1990 and 2010, a total of 146 patients underwent curative-intent resection of hilar cholangiocarcinoma with regional lymphadenectomy at two university medical centers in the Netherlands. Ninety-one patients (62 %) without lymph node metastases at routine histology were included. Micrometastases were identified by multiple sectioning of all lymph nodes and additional immunostaining with an antibody against cytokeratin 19 (K19). The association with overall survival was assessed in univariable and multivariable analysis. Median follow-up was 48 months. RESULTS: Micrometastases were identified in 16 (5 %) of 324 lymph nodes, corresponding to 11 (12 %) of 91 patients. There were no differences in clinical variables between K19 lymph node-positive and -negative patients. Five-year survival rates in patients with lymph node micrometastases were significantly lower compared to patients without micrometastases (27 vs. 54 %, P = 0.01). Multivariable analysis confirmed micrometastases as an independent prognostic factor for survival (adjusted Hazard ratio 2.4, P = 0.02). CONCLUSIONS: Lymph node micrometastases are associated with worse survival after resection of hilar cholangiocarcinoma. Immunohistochemical detection of lymph node micrometastases leads to better staging of patients who were initially diagnosed with node-negative (pN0) hilar cholangiocarcinoma on routine histology.","Source":"PubMed","category":"HUMAN","training_data":"Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma BACKGROUND: Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of this study was to assess the effect on survival of immunohistochemically detected lymph node micrometastases in patients with node-negative (pN0) hilar cholangiocarcinoma on routine histology. METHODS: Between 1990 and 2010, a total of 146 patients underwent curative-intent resection of hilar cholangiocarcinoma with regional lymphadenectomy at two university medical centers in the Netherlands. Ninety-one patients (62 %) without lymph node metastases at routine histology were included. Micrometastases were identified by multiple sectioning of all lymph nodes and additional immunostaining with an antibody against cytokeratin 19 (K19). The association with overall survival was assessed in univariable and multivariable analysis. Median follow-up was 48 months. RESULTS: Micrometastases were identified in 16 (5 %) of 324 lymph nodes, corresponding to 11 (12 %) of 91 patients. There were no differences in clinical variables between K19 lymph node-positive and -negative patients. Five-year survival rates in patients with lymph node micrometastases were significantly lower compared to patients without micrometastases (27 vs. 54 %, P = 0.01). Multivariable analysis confirmed micrometastases as an independent prognostic factor for survival (adjusted Hazard ratio 2.4, P = 0.02). CONCLUSIONS: Lymph node micrometastases are associated with worse survival after resection of hilar cholangiocarcinoma. Immunohistochemical detection of lymph node micrometastases leads to better staging of patients who were initially diagnosed with node-negative (pN0) hilar cholangiocarcinoma on routine histology. PubMed","prediction_labels":"HUMAN"},{"cleaned":"adequacy lymph node retrieval ampullary cancer association improved staging survival background aim present study determine optimal number lymph nodes ln examined stage pn0 tumors surgery ampulla vater carcinoma avc methods reviewed retrospectively 127 patients avc underwent pancreaticoduodenectomy 1990 2008 univariate multivariate analysis performed results fifty nine patients 46 5 pn0 whereas 68 patients 53 5 pn1 5 year disease specific survival dss worse pn1 patients pn0 patients 46 vs 77 p 0 0001 pn0 cohort optimal cut number ln analyzed found 12 5 year dss patients 12 ln 50 compared 89 12 ln p 0 001 multivariate analysis ln count 12 independent predictor associated improved survival hr 0 16 p 0 003 among pn0 patients among pn1 patients ln count 12 associated significantly better 5 year dss 59 vs 22 p 0 027 patients lymph node ratio lnr 0 20 5 year dss 24 compared 58 0 lnr 0 20 p 0 038 conclusions removal 12 ln examination associated improved survival rate surgery avc pn0 pn1 patients pubmed","probabilities":0.9799733,"Title":"Adequacy of lymph node retrieval for ampullary cancer and its association with improved staging and survival","Abstract":"BACKGROUND: The aim of the present study was to determine the optimal number of lymph nodes (LN) examined to stage pN0 tumors after surgery for ampulla of Vater carcinoma (AVC). METHODS: We reviewed retrospectively 127 patients with AVC who underwent pancreaticoduodenectomy (1990-2008). Univariate and multivariate analysis was performed. RESULTS: Fifty-nine patients (46.5 %) were pN0, whereas 68 patients (53.5 %) were pN1. The 5-year disease-specific survival (DSS) was worse for pN1 patients than for pN0 patients (46 vs. 77 %; P < 0.0001). In the pN0 cohort, the optimal cut-off number of LN analyzed was found to be 12. The 5-year DSS for patients with ≤ 12 LN was 50 %, compared with 89 % in those with >12 LN (P = 0.001). By multivariate analysis, a LN count >12 was the only independent predictor associated with improved survival (HR 0.16, P = 0.003) among pN0 patients. Among pN1 patients, a LN count >12 was associated with a significantly better 5-year DSS (59 vs. 22 %; P = 0.027). Patients with a lymph node ratio (LNR) >0.20 had a 5-year DSS of 24 %, compared with 58 % in those with 0 < LNR ≤ 0.20 (P = 0.038). CONCLUSIONS: Removal of more than 12 LN for examination is associated with improved survival rate after surgery for AVC in both pN0 and pN1 patients.","Source":"PubMed","category":"HUMAN","training_data":"Adequacy of lymph node retrieval for ampullary cancer and its association with improved staging and survival BACKGROUND: The aim of the present study was to determine the optimal number of lymph nodes (LN) examined to stage pN0 tumors after surgery for ampulla of Vater carcinoma (AVC). METHODS: We reviewed retrospectively 127 patients with AVC who underwent pancreaticoduodenectomy (1990-2008). Univariate and multivariate analysis was performed. RESULTS: Fifty-nine patients (46.5 %) were pN0, whereas 68 patients (53.5 %) were pN1. The 5-year disease-specific survival (DSS) was worse for pN1 patients than for pN0 patients (46 vs. 77 %; P < 0.0001). In the pN0 cohort, the optimal cut-off number of LN analyzed was found to be 12. The 5-year DSS for patients with ≤ 12 LN was 50 %, compared with 89 % in those with >12 LN (P = 0.001). By multivariate analysis, a LN count >12 was the only independent predictor associated with improved survival (HR 0.16, P = 0.003) among pN0 patients. Among pN1 patients, a LN count >12 was associated with a significantly better 5-year DSS (59 vs. 22 %; P = 0.027). Patients with a lymph node ratio (LNR) >0.20 had a 5-year DSS of 24 %, compared with 58 % in those with 0 < LNR ≤ 0.20 (P = 0.038). CONCLUSIONS: Removal of more than 12 LN for examination is associated with improved survival rate after surgery for AVC in both pN0 and pN1 patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatopancreatoduodenectomy acceptable operation biliary cancer hepatopancreatoduodenectomy hpd usually indicated resection locally advanced bile duct bd cancer gallbladder gb cancer previous studies demonstrated favorable survival rate bd cancer patients hpd r0 resection achieved contrast benefit hpd gb cancer remains controversial study aimed analyze outcomes gb bd cancer hpd january 2004 december 2013 total 22 patients underwent hpd bd n 14 gb cancer n 8 analyzed survival mortality morbidity prognostic factors hpd mortality rate 4 5 per cent morbidity rate 68 2 per cent pancreatic fistula occurred 50 0 per cent patients grade 40 9 grade b 9 1 liver failure occur 1 3 5 year survival rates bd cancer patients 57 1 17 9 17 9 per cent gb cancer patients 62 5 25 0 25 0 per cent respectively p 0 768 bd cancer significant prognostic factors tumor size portal vein invasion multiple lymph node metastases operation time furthermore bd cancer patients three risk factors showed poorer survival fewer three risk factors hpd gb bd cancer performed acceptable mortality morbidity rates gb cancer patients underwent hpd showed comparable survival rates compared bd cancer patients long term survival achieved selected patients bd cancer pubmed","probabilities":0.9799733,"Title":"Is Hepatopancreatoduodenectomy an Acceptable Operation for Biliary Cancer?","Abstract":"Hepatopancreatoduodenectomy (HPD) is usually indicated for the resection of locally advanced bile duct (BD) cancer or gallbladder (GB) cancer. Previous studies have demonstrated a favorable survival rate in BD cancer patients after HPD if R0 resection is achieved. By contrast, the benefit of HPD for GB cancer remains controversial. This study aimed to analyze the outcomes of GB and BD cancer after HPD. Between January 2004 and December 2013, a total of 22 patients underwent HPD for BD (n = 14) or GB cancer (n = 8). We analyzed the survival, mortality, morbidity, and prognostic factors. After HPD, the mortality rate was 4.5 per cent and the morbidity rate was 68.2 per cent. Pancreatic fistula occurred in 50.0 per cent of the patients (grade A, 40.9%; grade B, 9.1%). Liver failure did not occur. The 1-, 3-, and 5-year survival rates for BD cancer patients were 57.1, 17.9, and 17.9 per cent and those for GB cancer patients were 62.5, 25.0, and 25.0 per cent, respectively (P = 0.768). In BD cancer, significant prognostic factors were tumor size, portal vein invasion, multiple lymph node metastases, and operation time. Furthermore, BD cancer patients with three or more of risk factors showed poorer survival than those with fewer than three risk factors. HPD for GB and BD cancer can be performed with acceptable mortality and morbidity rates. GB cancer patients who underwent HPD showed comparable survival rates compared with BD cancer patients. Long-term survival can be achieved in selected patients with BD cancer.","Source":"PubMed","category":"HUMAN","training_data":"Is Hepatopancreatoduodenectomy an Acceptable Operation for Biliary Cancer? Hepatopancreatoduodenectomy (HPD) is usually indicated for the resection of locally advanced bile duct (BD) cancer or gallbladder (GB) cancer. Previous studies have demonstrated a favorable survival rate in BD cancer patients after HPD if R0 resection is achieved. By contrast, the benefit of HPD for GB cancer remains controversial. This study aimed to analyze the outcomes of GB and BD cancer after HPD. Between January 2004 and December 2013, a total of 22 patients underwent HPD for BD (n = 14) or GB cancer (n = 8). We analyzed the survival, mortality, morbidity, and prognostic factors. After HPD, the mortality rate was 4.5 per cent and the morbidity rate was 68.2 per cent. Pancreatic fistula occurred in 50.0 per cent of the patients (grade A, 40.9%; grade B, 9.1%). Liver failure did not occur. The 1-, 3-, and 5-year survival rates for BD cancer patients were 57.1, 17.9, and 17.9 per cent and those for GB cancer patients were 62.5, 25.0, and 25.0 per cent, respectively (P = 0.768). In BD cancer, significant prognostic factors were tumor size, portal vein invasion, multiple lymph node metastases, and operation time. Furthermore, BD cancer patients with three or more of risk factors showed poorer survival than those with fewer than three risk factors. HPD for GB and BD cancer can be performed with acceptable mortality and morbidity rates. GB cancer patients who underwent HPD showed comparable survival rates compared with BD cancer patients. Long-term survival can be achieved in selected patients with BD cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role micrornas intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc second common primary hepatic malignancy poor prognosis despite improvements diagnosis therapy prognosis icc patients remains poor improved understanding icc pathogenesis consequential identification novel therapeutic targets improve prognosis icc patients micrornas mirnas class highly conserved endogenous small non coding rna molecules 18 23 nucleotides length regulate gene expression complementary base pairing target messenger rnas subsequent gene silencing several studies shown deregulated expression mirnas icc cell lines tissues mirnas play important roles icc apoptosis cell proliferation invasion migration metastasis review illustrate potential role mirna pathogenesis icc explore possibilities using mirnas prognostic diagnostic markers well therapeutic targets icc pubmed","probabilities":0.875,"Title":"The role of microRNAs in intrahepatic cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy with poor prognosis. Despite improvements in its diagnosis and therapy, the prognosis for ICC patients remains poor. An improved understanding of ICC pathogenesis and consequential identification of novel therapeutic targets would improve the prognosis of ICC patients. MicroRNAs (miRNAs) are a class of highly conserved, endogenous, small non-coding RNA molecules of 18-23 nucleotides in length, which regulate gene expression through complementary base-pairing with target messenger RNAs and subsequent gene silencing. Several studies have shown deregulated expression of miRNAs in ICC cell lines and tissues, in which these miRNAs play important roles in ICC apoptosis, cell proliferation, invasion, migration and metastasis. In this review, we illustrate the potential role of miRNA in the pathogenesis of ICC and explore the possibilities of using miRNAs as prognostic and diagnostic markers, as well as therapeutic targets in ICC.","Source":"PubMed","category":"HUMAN","training_data":"The role of microRNAs in intrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy with poor prognosis. Despite improvements in its diagnosis and therapy, the prognosis for ICC patients remains poor. An improved understanding of ICC pathogenesis and consequential identification of novel therapeutic targets would improve the prognosis of ICC patients. MicroRNAs (miRNAs) are a class of highly conserved, endogenous, small non-coding RNA molecules of 18-23 nucleotides in length, which regulate gene expression through complementary base-pairing with target messenger RNAs and subsequent gene silencing. Several studies have shown deregulated expression of miRNAs in ICC cell lines and tissues, in which these miRNAs play important roles in ICC apoptosis, cell proliferation, invasion, migration and metastasis. In this review, we illustrate the potential role of miRNA in the pathogenesis of ICC and explore the possibilities of using miRNAs as prognostic and diagnostic markers, as well as therapeutic targets in ICC. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"radioembolization cost effective intrahepatic cholangiocarcinoma seermedicare population study purpose analyze cost effectiveness radioembolization treatment intrahepatic cholangiocarcinoma icc using surveillance epidemiology end results seer medicare cancer database materials methods cost measured total treatment related reimbursement patients diagnosed icc received chemotherapy alone chemotherapy yttrium 90 radioembolization assessed seer medicare cancer database 1999 2012 survival analysis performed incremental cost effectiveness ratios generated results study included 585 patients average age diagnosis 71 years standard deviation 9 9 52 patients male twelve percent patients received chemotherapy radioembolization n 72 88 patients n 513 received chemotherapy median survival 1043 days 95 confidence interval ci 894 1244 chemotherapy plus radioembolization 811 days 95 ci 705 925 chemotherapy alone p 02 patients received combination therapy slightly younger 71 vs 69 years p 03 significant differences observed treatment groups age treatment sex race city size multivariable analysis showed hazard ratio progression combination therapy versus chemotherapy alone 0 76 95 ci 0 59 0 97 p 029 incremental cost effectiveness ratio measure cost added year life 50 058 65 per year quartiles 11 454 63 52 763 28 conclusions combination therapy icc chemotherapy radioembolization associated higher median survival cost effective treatment median cost 50 058 65 per additional year survival stn","probabilities":0.9799733,"Title":"Radioembolization Is Cost Effective In Intrahepatic Cholangiocarcinoma: A Seermedicare Population Study","Abstract":"Purpose: To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database. \r\n\r\n Materials and methods: Cost as measured by total treatment-related reimbursement in patients diagnosed with ICC who received chemotherapy alone or chemotherapy and yttrium-90 radioembolization was assessed in the SEER Medicare cancer database (1999-2012). Survival analysis was performed, and incremental cost-effectiveness ratios were generated. \r\n\r\n Results: The study included 585 patients. Average age at diagnosis was 71 years (standard deviation: 9.9), and 52% of patients were male. Twelve percent of patients received chemotherapy with radioembolization (n = 72), and 88% of patients (n = 513) received only chemotherapy. Median survival was 1043 days (95% confidence interval [CI]: 894-1244) for chemotherapy plus radioembolization and 811 days (95% CI: 705-925) for chemotherapy alone (P = .02). Patients who received combination therapy were slightly younger (71 vs 69 years, P = .03). No significant differences were observed between treatment groups in age at treatment, sex, race, or city size. Multivariable analysis showed a hazard ratio for progression for combination therapy versus chemotherapy alone of 0.76 (95% CI: 0.59-0.97, P = .029). The incremental cost-effectiveness ratio, a measure of cost of each added year of life, was $50,058.65 per year (quartiles: $11,454.63, $52,763.28). \r\n\r\n Conclusions: Combination therapy of ICC with chemotherapy and radioembolization is associated with higher median survival and can be a cost-effective treatment, with a median cost of $50,058.65 per additional year of survival.","Source":"STN","category":"HUMAN","training_data":"Radioembolization Is Cost Effective In Intrahepatic Cholangiocarcinoma: A Seermedicare Population Study Purpose: To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database. \r\n\r\n Materials and methods: Cost as measured by total treatment-related reimbursement in patients diagnosed with ICC who received chemotherapy alone or chemotherapy and yttrium-90 radioembolization was assessed in the SEER Medicare cancer database (1999-2012). Survival analysis was performed, and incremental cost-effectiveness ratios were generated. \r\n\r\n Results: The study included 585 patients. Average age at diagnosis was 71 years (standard deviation: 9.9), and 52% of patients were male. Twelve percent of patients received chemotherapy with radioembolization (n = 72), and 88% of patients (n = 513) received only chemotherapy. Median survival was 1043 days (95% confidence interval [CI]: 894-1244) for chemotherapy plus radioembolization and 811 days (95% CI: 705-925) for chemotherapy alone (P = .02). Patients who received combination therapy were slightly younger (71 vs 69 years, P = .03). No significant differences were observed between treatment groups in age at treatment, sex, race, or city size. Multivariable analysis showed a hazard ratio for progression for combination therapy versus chemotherapy alone of 0.76 (95% CI: 0.59-0.97, P = .029). The incremental cost-effectiveness ratio, a measure of cost of each added year of life, was $50,058.65 per year (quartiles: $11,454.63, $52,763.28). \r\n\r\n Conclusions: Combination therapy of ICC with chemotherapy and radioembolization is associated with higher median survival and can be a cost-effective treatment, with a median cost of $50,058.65 per additional year of survival. STN","prediction_labels":"HUMAN"},{"cleaned":"translational approach standardization machine perfusion adoption ex vivo liver resection background hepatic resection represents best treatment primary metastatic liver tumors always feasible early 1980 piclmayr described complex liver resection technique termed ex vivo liver resection treatment locally advanced tumors conventionally resectable authors approached technique translational research preclinical setting similarly reproduced human patients methods swine median xyphopubic laparotomy liver mobilized expose vena cava temporary porto caval shunt previously prepared back table using segment thoracic aorta vascular anastomosis supra hepatic vena cava caval graft quickly performed liver placed machine perfusion system continuously perfused 2 h final implantation orthotopically animal anastomoses performed usual based experience intervention reproduced human model 39 year old woman affected large intrahepatic cholangiocarcinoma considered unresectable results animals survived procedure peak aspartate aminotransferase level 460 87 u l recorded 60 min reperfusion lactate levels flared 120 min 3 6 0 2 mmol l clinical case postoperative period uneventful patient discharged day 22 conclusions described procedure feasible surgeons transplantation background study showed translational approach enhances surgeon ability perform intervention systematically shorter time good outcome stn","probabilities":1.0,"Title":"A Translational Approach To Standardization Of Machine Perfusion Adoption In Ex Vivo Liver Resection","Abstract":"Background: Hepatic resection represents the best treatment for primary and metastatic liver tumors but is not always feasible. In early 1980, Piclmayr described a complex liver resection technique, termed \"ex vivo liver resection,\" for the treatment of locally advanced tumors not conventionally resectable. The authors approached this technique with translational research in a preclinical setting and then similarly reproduced it in human patients. \r\n\r\n Methods: In the swine median xyphopubic laparotomy, the liver was mobilized to expose the vena cava. A temporary porto-caval shunt was previously prepared on the back table using a segment of thoracic aorta, and a vascular anastomosis between the supra-hepatic vena cava and a caval graft was quickly performed. The liver was placed in a machine perfusion system and continuously perfused for 2 h for its final implantation orthotopically in the same animal. The anastomoses were performed as usual. Based on this experience, the intervention was reproduced in the human model of a 39-year-old woman affected by large intrahepatic cholangiocarcinoma considered unresectable.' \r\n\r\n Results: All animals survived the procedure. The peak aspartate aminotransferase level (460 ± 87 U/L) was recorded 60 min after reperfusion. Lactate levels flared up for 120 min (3.6 ± 0.2 mmol/L). In the clinical case, the postoperative period was uneventful, and the patient was discharged on day 22. \r\n\r\n Conclusions: The described procedure is feasible only for surgeons with a transplantation background. The study showed that this translational approach enhances the surgeon's ability to perform the intervention systematically in a shorter time and with a good outcome.","Source":"STN","category":"ANIMAL","training_data":"A Translational Approach To Standardization Of Machine Perfusion Adoption In Ex Vivo Liver Resection Background: Hepatic resection represents the best treatment for primary and metastatic liver tumors but is not always feasible. In early 1980, Piclmayr described a complex liver resection technique, termed \"ex vivo liver resection,\" for the treatment of locally advanced tumors not conventionally resectable. The authors approached this technique with translational research in a preclinical setting and then similarly reproduced it in human patients. \r\n\r\n Methods: In the swine median xyphopubic laparotomy, the liver was mobilized to expose the vena cava. A temporary porto-caval shunt was previously prepared on the back table using a segment of thoracic aorta, and a vascular anastomosis between the supra-hepatic vena cava and a caval graft was quickly performed. The liver was placed in a machine perfusion system and continuously perfused for 2 h for its final implantation orthotopically in the same animal. The anastomoses were performed as usual. Based on this experience, the intervention was reproduced in the human model of a 39-year-old woman affected by large intrahepatic cholangiocarcinoma considered unresectable.' \r\n\r\n Results: All animals survived the procedure. The peak aspartate aminotransferase level (460 ± 87 U/L) was recorded 60 min after reperfusion. Lactate levels flared up for 120 min (3.6 ± 0.2 mmol/L). In the clinical case, the postoperative period was uneventful, and the patient was discharged on day 22. \r\n\r\n Conclusions: The described procedure is feasible only for surgeons with a transplantation background. The study showed that this translational approach enhances the surgeon's ability to perform the intervention systematically in a shorter time and with a good outcome. STN","prediction_labels":"ANIMAL"},{"cleaned":"calpain system protein expression carcinomas pancreas bile duct ampulla background pancreatic cancer including cancer ampulla vater bile duct aggressive poor five year survival rate improved methods patient stratification required methods assessed expression calpain 1 calpain 2 calpastatin two patient cohorts using immunohistochemistry tissue microarrays first cohort composed 68 pancreatic adenocarcinomas second cohort composed 120 cancers bile duct ampulla results bile duct ampullary carcinomas association observed cytoplasmic calpastatin expression patient age p 0 036 nuclear calpastatin expression increased tumour stage p 0 026 presence vascular invasion p 0 043 pancreatic cancer high calpain 2 expression significantly associated improved overall survival p 0 036 remained significant multivariate cox regression analysis hazard ratio 0 342 95 confidence interva l 0 157 0 741 p 0 007 cancers bile duct ampulla low cytoplasmic expression calpastatin significantly associated poor overall survival p 0 012 remained significant multivariate cox regression analysis hazard ratio 0 595 95 confidence interval 0 365 0 968 p 0 037 conclusion results suggest calpain 2 calpastatin expression important pancreatic cancers influencing disease progression findings study warrant larger follow study pubmed","probabilities":0.7966102,"Title":"Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla","Abstract":"BACKGROUND: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. METHODS: We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. RESULTS: In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037). CONCLUSION: The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study.","Source":"PubMed","category":"HUMAN","training_data":"Calpain system protein expression in carcinomas of the pancreas, bile duct and ampulla BACKGROUND: Pancreatic cancer, including cancer of the ampulla of Vater and bile duct, is very aggressive and has a poor five year survival rate; improved methods of patient stratification are required. METHODS: We assessed the expression of calpain-1, calpain-2 and calpastatin in two patient cohorts using immunohistochemistry on tissue microarrays. The first cohort was composed of 68 pancreatic adenocarcinomas and the second cohort was composed of 120 cancers of the bile duct and ampulla. RESULTS: In bile duct and ampullary carcinomas an association was observed between cytoplasmic calpastatin expression and patient age (P = 0.036), and between nuclear calpastatin expression and increased tumour stage (P = 0.026) and the presence of vascular invasion (P = 0.043). In pancreatic cancer, high calpain-2 expression was significantly associated with improved overall survival (P = 0.036), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.342; 95% confidence interva l = 0.157-0.741; P = 0.007). In cancers of the bile duct and ampulla, low cytoplasmic expression of calpastatin was significantly associated with poor overall survival (P = 0.012), which remained significant in multivariate Cox-regression analysis (hazard ratio = 0.595; 95% confidence interval = 0.365-0.968; P = 0.037). CONCLUSION: The results suggest that calpain-2 and calpastatin expression is important in pancreatic cancers, influencing disease progression. The findings of this study warrant a larger follow-up study. PubMed","prediction_labels":"HUMAN"},{"cleaned":"management occluded metallic stents malignant hilar biliary stricture background aims little known management occluded multiple metallic stent ms deployed malignant hilar biliary strictures hbs purpose study evaluate endoscopic management occluded multiple mss deployed hbs methodology fifty five patients unresectable biliary tract carcinoma multiple mss inserted due hbs endoscopic intervention duodenal papilla performed 30 cases ms occlusion procedure success rate survival time procedure number endoscopic interventions death analyzed retrospectively results causes ms obstruction tissue ingrowth n 20 sludge n 7 tumor overgrowth n 2 hemobilia n 1 endoscopic cleaning deployment plastic stents metallic stents performed patients successfully accomplished via transpapillary approach survival time ms obstruction 219 days median number endoscopic interventions death 3 median interval endoscopic intervention first plastic stent occlusion 84 days conclusions long term data regarding endoscopic management occluded mss deployed malignant hilar biliary strictures acceptable although patency time plastic stents deployed ms occlusion relatively short pubmed","probabilities":0.7966102,"Title":"Management of occluded metallic stents in malignant hilar biliary stricture","Abstract":"BACKGROUND/AIMS: Little is known about the management of occluded multiple metallic stent (MS) deployed in malignant hilar biliary strictures (HBS). The purpose of this study was to evaluate the endoscopic management of occluded multiple MSs deployed in HBS. METHODOLOGY: Fifty-five patients with unresectable biliary tract carcinoma had multiple MSs inserted due to HBS. The endoscopic intervention through the duodenal papilla was performed on 30 cases that had MS occlusion. The procedure success rate, the survival time after the procedure and the number of endoscopic interventions before death were analyzed, retrospectively. RESULTS: The causes of MS obstruction were tissue ingrowth (n=20), sludge (n=7), tumor overgrowth (n=2), and hemobilia (n=1). Endoscopic cleaning or deployment of plastic stents or metallic stents was performed on these patients and was successfully accomplished only via the transpapillary approach. The survival time after MS obstruction was 219 days. The median number of endoscopic interventions before death was 3. The median interval of endoscopic intervention after the first plastic stent occlusion was 84 days. CONCLUSIONS: Our long-term data regarding the endoscopic management of occluded MSs deployed in malignant hilar biliary strictures are acceptable although the patency time of plastic stents deployed after MS occlusion was relatively short.","Source":"PubMed","category":"HUMAN","training_data":"Management of occluded metallic stents in malignant hilar biliary stricture BACKGROUND/AIMS: Little is known about the management of occluded multiple metallic stent (MS) deployed in malignant hilar biliary strictures (HBS). The purpose of this study was to evaluate the endoscopic management of occluded multiple MSs deployed in HBS. METHODOLOGY: Fifty-five patients with unresectable biliary tract carcinoma had multiple MSs inserted due to HBS. The endoscopic intervention through the duodenal papilla was performed on 30 cases that had MS occlusion. The procedure success rate, the survival time after the procedure and the number of endoscopic interventions before death were analyzed, retrospectively. RESULTS: The causes of MS obstruction were tissue ingrowth (n=20), sludge (n=7), tumor overgrowth (n=2), and hemobilia (n=1). Endoscopic cleaning or deployment of plastic stents or metallic stents was performed on these patients and was successfully accomplished only via the transpapillary approach. The survival time after MS obstruction was 219 days. The median number of endoscopic interventions before death was 3. The median interval of endoscopic intervention after the first plastic stent occlusion was 84 days. CONCLUSIONS: Our long-term data regarding the endoscopic management of occluded MSs deployed in malignant hilar biliary strictures are acceptable although the patency time of plastic stents deployed after MS occlusion was relatively short. PubMed","prediction_labels":"HUMAN"},{"cleaned":"risk bile duct cancer among printing workers exposed 1 2 dichloropropane dichloromethane objectives conducted retrospective cohort study examine risk bile duct cancer among current former workers offset color proof printing department printing company osaka japan methods standardized incidence ratios sirs january 1 1985 december 31 2012 estimated cumulative years exposure two chemicals dichloromethane dcm 1 2 dichloropropane 1 2 dcp using national incidence level reference addition examined risk patterns calendar year observation started results among 106 workers total 1 452 4 person years exposure 17 bile duct cancer cases observed resulting estimated overall sir 1 132 5 95 confidence interval ci 659 7 1 813 2 sir 1 319 9 95 ci 658 9 2 361 7 exposed dcm 1 2 dcp 1 002 8 95 ci 368 0 2 182 8 exposed 1 2 dcp sirs tended increase according years exposure 1 2 dcp dcm 5 year lag time assumed sirs higher cohorts observation started 1993 2000 particularly cohorts started 1996 1999 compared started 1993 2000 conclusions observed extraordinarily high risk bile duct cancer among offset color proof printing workers elevated risk may related cumulative exposure 1 2 dcp remains possibility portion risk due unidentified substances pubmed","probabilities":0.9799733,"Title":"Risk of bile duct cancer among printing workers exposed to 1,2-dichloropropane and/or dichloromethane","Abstract":"OBJECTIVES: We conducted a retrospective cohort study to examine the risk of bile duct cancer among current and former workers in the offset color proof printing department at a printing company in Osaka, Japan. METHODS: Standardized incidence ratios (SIRs) between January 1, 1985, and December 31, 2012, were estimated for the cumulative years of exposure to two chemicals, dichloromethane (DCM) and 1,2-dichloropropane (1,2-DCP), using the national incidence level as a reference. In addition, we examined risk patterns by the calendar year in which observation started. RESULTS: Among 106 workers with a total of 1,452.4 person-years of exposure, 17 bile duct cancer cases were observed, resulting in an estimated overall SIR of 1,132.5 (95% confidence interval (CI): 659.7-1,813.2). The SIR was 1,319.9 (95% CI: 658.9-2,361.7) for those who were exposed to both DCM and 1,2-DCP, and it was 1,002.8 (95% CI: 368.0-2,182.8) for those exposed to 1,2-DCP only. SIRs tended to increase according to years of exposure to 1,2-DCP but not DCM when a 5-year lag time was assumed. The SIRs were higher for the cohorts in which observation started in 1993-2000, particularly in cohorts in which it started in 1996-1999, compared with those in which it started before or after 1993-2000. CONCLUSIONS: We observed an extraordinarily high risk of bile duct cancer among the offset color proof printing workers. Elevated risk may be related to cumulative exposure to 1,2-DCP, but there remains some possibility that a portion of the risk is due to other unidentified substances.","Source":"PubMed","category":"HUMAN","training_data":"Risk of bile duct cancer among printing workers exposed to 1,2-dichloropropane and/or dichloromethane OBJECTIVES: We conducted a retrospective cohort study to examine the risk of bile duct cancer among current and former workers in the offset color proof printing department at a printing company in Osaka, Japan. METHODS: Standardized incidence ratios (SIRs) between January 1, 1985, and December 31, 2012, were estimated for the cumulative years of exposure to two chemicals, dichloromethane (DCM) and 1,2-dichloropropane (1,2-DCP), using the national incidence level as a reference. In addition, we examined risk patterns by the calendar year in which observation started. RESULTS: Among 106 workers with a total of 1,452.4 person-years of exposure, 17 bile duct cancer cases were observed, resulting in an estimated overall SIR of 1,132.5 (95% confidence interval (CI): 659.7-1,813.2). The SIR was 1,319.9 (95% CI: 658.9-2,361.7) for those who were exposed to both DCM and 1,2-DCP, and it was 1,002.8 (95% CI: 368.0-2,182.8) for those exposed to 1,2-DCP only. SIRs tended to increase according to years of exposure to 1,2-DCP but not DCM when a 5-year lag time was assumed. The SIRs were higher for the cohorts in which observation started in 1993-2000, particularly in cohorts in which it started in 1996-1999, compared with those in which it started before or after 1993-2000. CONCLUSIONS: We observed an extraordinarily high risk of bile duct cancer among the offset color proof printing workers. Elevated risk may be related to cumulative exposure to 1,2-DCP, but there remains some possibility that a portion of the risk is due to other unidentified substances. PubMed","prediction_labels":"HUMAN"},{"cleaned":"promising prediction model survival gallbladder carcinoma patients pretreatment prognostic nutrient index pretreatment nutritional immunological status play indispensable roles predicting outcome patients various types malignancies aim study investigate whether preoperative prognostic nutritional index pni simply accounts nutritional immunological status associated overall survival os patients gallbladder carcinoma gbc retrospective study included total 315 gbc patients surgery 2002 2012 pni calculated according following formula 10 serum albumin g dl 0 005 total lymphocyte count per mm3 receiver operating characteristic roc curve survival prediction plotted verify optimal cutoff value lmr set 46 14 according value patients categorized two different groups namely high pni group n 133 low pni group n 182 univariate multivariate cox regression models used identify independent prognostic factors results showed low pretreatment pni value significantly associated elderly age partial surgery procedure advanced tumor status tumor stage node stage tumor node metastasis stage p 0 05 low pni group worse os compare high pni group p 0 05 via univariate multivariate analyses pretreatment pni identified independent prognostic factor os hr 0 613 95 ci 0 448 0 838 p 0 001 subgroup analyses revealed pni significantly associated postoperative os independent tumor node metastasis stage surgical procedure conclusion pretreatment pni might serve effective predictor evaluate prognosis gbc patients surgery based findings pni characterized accessibility objectivity noninvasiveness included routine assessment gbc stn","probabilities":0.9799733,"Title":"A Promising Prediction Model For Survival In Gallbladder Carcinoma Patients: Pretreatment Prognostic Nutrient Index","Abstract":"The pretreatment nutritional and immunological status play indispensable roles in predicting the outcome of patients with various types of malignancies. The aim of the study was to investigate whether preoperative prognostic nutritional index (PNI), which simply accounts for nutritional and immunological status, was associated with overall survival (OS) in patients with gallbladder carcinoma (GBC). The retrospective study included a total of 315 GBC patients after surgery between 2002 and 2012. PNI was calculated according to the following formula: 10× serum albumin (g/dl) +0.005× total lymphocyte count (per mm3). A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff value for LMR, which was set at 46.14. According the value, patients were categorized into two different groups, namely high-PNI group (n = 133) and low-PNI group (n = 182). The univariate and multivariate Cox regression models were used to identify the independent prognostic factors. The results showed that low pretreatment PNI value was significantly associated with elderly age, partial surgery procedure, and advanced tumor status such as tumor stage, node stage, and tumor-node-metastasis stage (P < 0.05). The low-PNI group had a worse OS compare with the high-PNI group (P < 0.05). Via univariate and multivariate analyses, pretreatment PNI was identified as an independent prognostic factor for OS [HR: 0.613; 95%CI: 0.448-0.838; P < 0.001]. Subgroup analyses further revealed that PNI was significantly associated with postoperative OS independent of tumor node metastasis stage and surgical procedure. In conclusion, pretreatment PNI might serve as an effective predictor to evaluate prognosis of GBC patients after surgery. Based on the findings, PNI, characterized with accessibility, objectivity and noninvasiveness, should be included in the routine assessment of GBC.","Source":"STN","category":"HUMAN","training_data":"A Promising Prediction Model For Survival In Gallbladder Carcinoma Patients: Pretreatment Prognostic Nutrient Index The pretreatment nutritional and immunological status play indispensable roles in predicting the outcome of patients with various types of malignancies. The aim of the study was to investigate whether preoperative prognostic nutritional index (PNI), which simply accounts for nutritional and immunological status, was associated with overall survival (OS) in patients with gallbladder carcinoma (GBC). The retrospective study included a total of 315 GBC patients after surgery between 2002 and 2012. PNI was calculated according to the following formula: 10× serum albumin (g/dl) +0.005× total lymphocyte count (per mm3). A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimal cutoff value for LMR, which was set at 46.14. According the value, patients were categorized into two different groups, namely high-PNI group (n = 133) and low-PNI group (n = 182). The univariate and multivariate Cox regression models were used to identify the independent prognostic factors. The results showed that low pretreatment PNI value was significantly associated with elderly age, partial surgery procedure, and advanced tumor status such as tumor stage, node stage, and tumor-node-metastasis stage (P < 0.05). The low-PNI group had a worse OS compare with the high-PNI group (P < 0.05). Via univariate and multivariate analyses, pretreatment PNI was identified as an independent prognostic factor for OS [HR: 0.613; 95%CI: 0.448-0.838; P < 0.001]. Subgroup analyses further revealed that PNI was significantly associated with postoperative OS independent of tumor node metastasis stage and surgical procedure. In conclusion, pretreatment PNI might serve as an effective predictor to evaluate prognosis of GBC patients after surgery. Based on the findings, PNI, characterized with accessibility, objectivity and noninvasiveness, should be included in the routine assessment of GBC. STN","prediction_labels":"HUMAN"},{"cleaned":"frequency cholecystectomy affect ensuing incidence gallbladder cancer sweden population based study 16 year coverage background gallbladder cancer gbc rare among different gastrointestinal cancers significant global variation incidence high cholecystectomy rates benign indications assumed prevent development gallbladder cancer aim present study explore relationship rate cholecystectomy different time periods regions country annual incidence gbc methods standardized cholecystectomy gbc incidences swedish counties obtained swedish national inpatient national cancer registries years 1998 2013 incidences calculated ages 15 years per 100 000 population relationships cholecystectomy gbc incidences analyzed using regression models correlation analyses performed total cumulative incidence rates well incidence rates calculated first last 8 years entire study period results cholecystectomy rates ranged 99 205 per 100 000 year gbc incidence 2 3 5 1 overall observed slow steady decline cholecystectomy rates well gbc incidences 16 year period significant correlation cholecystectomy rates gbc incidences seen conclusions nationwide population based study demonstrates substantial geographic differences annual cholecystectomy rates without significant inverse co variation cholecystectomy rates ensuing gbc incidence supported idea frequent cholecystectomy affects incidence gbc stn","probabilities":0.9799733,"Title":"Does The Frequency Of Cholecystectomy Affect The Ensuing Incidence Of Gallbladder Cancer In Sweden? A Population-Based Study With A 16-Year Coverage","Abstract":"Background: Gallbladder cancer (GBC) is rare among the different gastrointestinal cancers with a significant global variation in incidence. High cholecystectomy rates on benign indications have been assumed to prevent the development of gallbladder cancer. The aim of the present study was to explore the relationship between the rate of cholecystectomy at different time periods and regions of the country and the annual incidence of GBC. \r\n\r\n Methods: Standardized cholecystectomy and GBC incidences for Swedish counties have been obtained from the Swedish national inpatient and National Cancer registries for the years 1998–2013. The incidences have been calculated for ages over 15 years and per 100,000 population. The relationships between cholecystectomy and GBC incidences have been analyzed using regression models. Correlation analyses were performed for the total cumulative incidence rates as well as the incidence rates calculated for the first and last 8 years of the entire study period. \r\n\r\n Results: Cholecystectomy rates ranged from 99 to 205 per 100,000 and year, and the GBC incidence from 2.3 to 5.1. Overall, we observed a slow but steady decline in cholecystectomy rates—as well as GBC incidences during the 16-year period. No significant correlation between the cholecystectomy rates and GBC incidences was seen. \r\n\r\n Conclusions: This nationwide population-based study demonstrates substantial geographic differences in annual cholecystectomy rates without any significant inverse co-variation between cholecystectomy rates and the ensuing GBC incidence which would have supported the idea that frequent cholecystectomy affects the incidence of GBC.","Source":"STN","category":"HUMAN","training_data":"Does The Frequency Of Cholecystectomy Affect The Ensuing Incidence Of Gallbladder Cancer In Sweden? A Population-Based Study With A 16-Year Coverage Background: Gallbladder cancer (GBC) is rare among the different gastrointestinal cancers with a significant global variation in incidence. High cholecystectomy rates on benign indications have been assumed to prevent the development of gallbladder cancer. The aim of the present study was to explore the relationship between the rate of cholecystectomy at different time periods and regions of the country and the annual incidence of GBC. \r\n\r\n Methods: Standardized cholecystectomy and GBC incidences for Swedish counties have been obtained from the Swedish national inpatient and National Cancer registries for the years 1998–2013. The incidences have been calculated for ages over 15 years and per 100,000 population. The relationships between cholecystectomy and GBC incidences have been analyzed using regression models. Correlation analyses were performed for the total cumulative incidence rates as well as the incidence rates calculated for the first and last 8 years of the entire study period. \r\n\r\n Results: Cholecystectomy rates ranged from 99 to 205 per 100,000 and year, and the GBC incidence from 2.3 to 5.1. Overall, we observed a slow but steady decline in cholecystectomy rates—as well as GBC incidences during the 16-year period. No significant correlation between the cholecystectomy rates and GBC incidences was seen. \r\n\r\n Conclusions: This nationwide population-based study demonstrates substantial geographic differences in annual cholecystectomy rates without any significant inverse co-variation between cholecystectomy rates and the ensuing GBC incidence which would have supported the idea that frequent cholecystectomy affects the incidence of GBC. STN","prediction_labels":"HUMAN"},{"cleaned":"autophagy suppression accelerates apoptosis induced norcantharidin cholangiocarcinoma norcantharidin cantharidin demethylated analog antitumor effects many tumors including cholangiocarcinoma autophagy suppression known increase chemosensitivity cholangiocarcinoma study aimed determine whether autophagy suppression accelerates apoptosis induced norcantharidin human cholangiocarcinoma cells human cholangiocarcinoma cell line qbc939 incubated rpmi 1640 medium without norcantharidin autophagy induced using hbss media ca2 mg2 supported 10 mm hepes suppressed treatment 3 ma transfection sirna atg5 comparison drawn conditions mitochondrial membrane potential disturbance levels reactive oxygen species ros apoptotic proteins apoptosis cholangiocarcinoma cell apoptosis accelerated norcantharidin autophagy suppression regulated norcantharidin pro apoptotic effect autophagy induction weakened apoptosis accelerated ros production regulated bax protein expression cytochrome c levels localization mitochondrial membrane disturbance levels caspase 9 caspase 3 cleaved parp higher autophagy suppressed regulated autophagy induced sum found norcantharidin induced cholangiocarcinoma cell death autophagy suppression enhanced pro apoptotic action norcantharidin appears involve mitochondrial apoptosis pathway activation ros generation stn","probabilities":0.9467213,"Title":"Autophagy Suppression Accelerates Apoptosis Induced By Norcantharidin In Cholangiocarcinoma","Abstract":"Norcantharidin is a cantharidin demethylated analog with antitumor effects in many tumors, including cholangiocarcinoma. Autophagy suppression is known to increase chemosensitivity in cholangiocarcinoma. This study aimed to determine whether autophagy suppression accelerates apoptosis induced by norcantharidin in human cholangiocarcinoma cells. The human cholangiocarcinoma cell line QBC939 was incubated in RPMI 1640 medium with or without norcantharidin. Autophagy was induced using HBSS media with Ca2+ and Mg2+ supported by 10 mM HEPES or suppressed by treatment with 3-MA or transfection with siRNA against Atg5. The comparison was drawn between these conditions in mitochondrial membrane potential disturbance, the levels of reactive oxygen species (ROS), apoptotic proteins, and apoptosis. Cholangiocarcinoma cell apoptosis was accelerated by norcantharidin. Autophagy suppression up-regulated norcantharidin's pro-apoptotic effect, but autophagy induction weakened it. As apoptosis was accelerated, ROS production was up-regulated. Bax protein expression, cytochrome c levels and localization, mitochondrial membrane disturbance, and the levels of caspase-9, caspase-3, and cleaved PARP were higher when autophagy was suppressed, and all of those were down-regulated when autophagy was induced. To sum up, it was found that norcantharidin induced cholangiocarcinoma cell death, and autophagy suppression enhanced the pro-apoptotic action of norcantharidin, which appears to involve the mitochondrial apoptosis pathway activation and ROS generation.","Source":"STN","category":"ANIMAL","training_data":"Autophagy Suppression Accelerates Apoptosis Induced By Norcantharidin In Cholangiocarcinoma Norcantharidin is a cantharidin demethylated analog with antitumor effects in many tumors, including cholangiocarcinoma. Autophagy suppression is known to increase chemosensitivity in cholangiocarcinoma. This study aimed to determine whether autophagy suppression accelerates apoptosis induced by norcantharidin in human cholangiocarcinoma cells. The human cholangiocarcinoma cell line QBC939 was incubated in RPMI 1640 medium with or without norcantharidin. Autophagy was induced using HBSS media with Ca2+ and Mg2+ supported by 10 mM HEPES or suppressed by treatment with 3-MA or transfection with siRNA against Atg5. The comparison was drawn between these conditions in mitochondrial membrane potential disturbance, the levels of reactive oxygen species (ROS), apoptotic proteins, and apoptosis. Cholangiocarcinoma cell apoptosis was accelerated by norcantharidin. Autophagy suppression up-regulated norcantharidin's pro-apoptotic effect, but autophagy induction weakened it. As apoptosis was accelerated, ROS production was up-regulated. Bax protein expression, cytochrome c levels and localization, mitochondrial membrane disturbance, and the levels of caspase-9, caspase-3, and cleaved PARP were higher when autophagy was suppressed, and all of those were down-regulated when autophagy was induced. To sum up, it was found that norcantharidin induced cholangiocarcinoma cell death, and autophagy suppression enhanced the pro-apoptotic action of norcantharidin, which appears to involve the mitochondrial apoptosis pathway activation and ROS generation. STN","prediction_labels":"ANIMAL"},{"cleaned":"definition t3 4 regional lymph nodes gallbladder cancer valid uicc japanese staging system background union international cancer control uicc japanese society biliary surgery jsbs staging systems differ staging gallbladder cancer define hepatic invasion without invasion another organ t3 either t3 t4 respectively posterosuperior pancreatic lymph node pspln metastases m1 n2 respectively methods retrospectively evaluated survival 224 patients undergone macroscopically curative resection gallbladder cancer assessed influence differences two staging systems survival results jsbs staging stratified survival curves better stages iii iv fifty seven patients classified uicc t3 jsbs t4 patients better survival 43 patients uicc t4 jsbs t4 comparable survival 17 patients uicc t3 jsbs t3 uicc stage iiib composed two subgroups u t2n1 18 patients u t3n1 21 patients 5 year survivals 85 41 respectively p 0 01 latter comparable 28 t3n0 patients 35 p 0 93 survival uicc m1 patients disease restricted psplns significantly better involvement beyond psplns 5 year survival 35 vs 17 p 0 04 conclusions although uicc staging accurately defines category jsbs staging better stratifies prognosis patients gallbladder cancer mainly uicc stage iiib includes t1 2n1m0 associated significantly better survival t3n0m0 appropriate classify psplns regional lymph nodes pubmed","probabilities":0.9799733,"Title":"Definition of T3/4 and regional lymph nodes in gallbladder cancer: which is more valid, the UICC or the Japanese staging system?","Abstract":"BACKGROUND: The Union for International Cancer Control (UICC) and Japanese Society of Biliary Surgery (JSBS) staging systems differ in their staging of gallbladder cancer: they define hepatic invasion with or without invasion of another organ as T3 and either T3 or T4, respectively, and posterosuperior pancreatic lymph node (PSPLN) metastases as M1 and N2, respectively. METHODS: We retrospectively evaluated the survival of 224 patients who had undergone macroscopically curative resection for gallbladder cancer and assessed the influence of the differences between the two staging systems on survival. RESULTS: JSBS staging stratified the survival curves better for stages III or IV. Fifty-seven patients were classified as UICC-T3 but JSBS-T4. These patients had better survival than did 43 patients with UICC-T4/JSBS-T4 and comparable survival to 17 patients with UICC-T3/JSBS-T3. UICC stage IIIB is composed of two subgroups: U-T2N1 (18 patients) and U-T3N1 (21 patients). Their 5-year survivals were 85 and 41%, respectively (P = 0.01). The latter was comparable to that of 28 T3N0 patients (35%, P = 0.93). The survival of the UICC-M1 patients with disease restricted to PSPLNs was significantly better than that of those with involvement beyond PSPLNs (5-year survival 35 vs. 17%; P = 0.04). CONCLUSIONS: Although UICC staging more accurately defines the T category, JSBS staging better stratifies the prognosis of patients with gallbladder cancer, mainly because UICC stage IIIB includes T1/2N1M0, which is associated with significantly better survival than T3N0M0. It would be appropriate to classify PSPLNs as regional lymph nodes.","Source":"PubMed","category":"HUMAN","training_data":"Definition of T3/4 and regional lymph nodes in gallbladder cancer: which is more valid, the UICC or the Japanese staging system? BACKGROUND: The Union for International Cancer Control (UICC) and Japanese Society of Biliary Surgery (JSBS) staging systems differ in their staging of gallbladder cancer: they define hepatic invasion with or without invasion of another organ as T3 and either T3 or T4, respectively, and posterosuperior pancreatic lymph node (PSPLN) metastases as M1 and N2, respectively. METHODS: We retrospectively evaluated the survival of 224 patients who had undergone macroscopically curative resection for gallbladder cancer and assessed the influence of the differences between the two staging systems on survival. RESULTS: JSBS staging stratified the survival curves better for stages III or IV. Fifty-seven patients were classified as UICC-T3 but JSBS-T4. These patients had better survival than did 43 patients with UICC-T4/JSBS-T4 and comparable survival to 17 patients with UICC-T3/JSBS-T3. UICC stage IIIB is composed of two subgroups: U-T2N1 (18 patients) and U-T3N1 (21 patients). Their 5-year survivals were 85 and 41%, respectively (P = 0.01). The latter was comparable to that of 28 T3N0 patients (35%, P = 0.93). The survival of the UICC-M1 patients with disease restricted to PSPLNs was significantly better than that of those with involvement beyond PSPLNs (5-year survival 35 vs. 17%; P = 0.04). CONCLUSIONS: Although UICC staging more accurately defines the T category, JSBS staging better stratifies the prognosis of patients with gallbladder cancer, mainly because UICC stage IIIB includes T1/2N1M0, which is associated with significantly better survival than T3N0M0. It would be appropriate to classify PSPLNs as regional lymph nodes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"evaluation inflammation based prognostic scores patients undergoing hepatobiliary resection perihilar cholangiocarcinoma background inflammation based prognostic scores prognostic value several kinds cancer however little known value perihilar cholangiocarcinoma evaluated whether inflammation based prognostic scores associated survival patients perihilar cholangiocarcinoma methods inflammation based scores e modified glasgow prognostic score mgps neutrophil lymphocyte ratio platelet lymphocyte ratio prognostic nutritional index retrospectively evaluated 534 patients underwent resection perihilar cholangiocarcinoma blood samples obtained 1 3 days surgery jaundice fully resolved biliary drainage cholangitis subsided used obtain scores results four scores evaluated mgps showed prognostic value whereas remaining three scores patients mgps 0 significantly better survival patients mgps 1 2 41 9 vs 26 3 5 years p 0 001 mgps 1 2 significantly associated higher incidence preoperative cholangitis node metastasis distant metastasis pm irrespective absence n 442 presence n 92 preoperative cholangitis survival patients mgps 0 significantly better patients mgps 1 2 multivariate analysis revealed mgps blood transfusion histologic grade curability r status lymph node metastasis distant metastasis independent prognostic factors conclusions solid cancers mgps independent prognostic factor resected perihilar cholangiocarcinoma simple inexpensive scoring system plays important role refining patient stratification predicting survival stn","probabilities":0.9799733,"Title":"Evaluation Of Inflammation-Based Prognostic Scores In Patients Undergoing Hepatobiliary Resection For Perihilar Cholangiocarcinoma","Abstract":"Background: Inflammation-based prognostic scores have prognostic value in several kinds of cancer. However, little is known about their value in perihilar cholangiocarcinoma. We evaluated whether inflammation-based prognostic scores are associated with survival of patients with perihilar cholangiocarcinoma. \r\n\r\n Methods: Inflammation-based scores (i.e., the modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and prognostic nutritional index) were retrospectively evaluated in 534 patients who underwent resection for perihilar cholangiocarcinoma. Blood samples obtained 1-3 days before surgery after jaundice had fully resolved with biliary drainage and after cholangitis had subsided were used to obtain the scores. \r\n\r\n Results: Of the four scores evaluated, the mGPS showed prognostic value, whereas the remaining three scores did not. Patients with an mGPS of 0 had significantly better survival than patients with an mGPS of 1 or 2 (41.9 % vs 26.3 % at 5 years, P < 0.001). An mGPS of 1 or 2 was significantly associated with a higher incidence of preoperative cholangitis, node metastasis, and distant metastasis (pM). Irrespective of the absence (n = 442) or presence (n = 92) of preoperative cholangitis, the survival of patients with an mGPS of 0 was significantly better than that of patients with an mGPS of 1 or 2. Multivariate analysis revealed that the mGPS, blood transfusion, histologic grade, curability (R status), lymph node metastasis, and distant metastasis were independent prognostic factors. \r\n\r\n Conclusions: As in other solid cancers, the mGPS is an independent prognostic factor in resected perihilar cholangiocarcinoma. This simple and inexpensive scoring system plays an important role in refining patient stratification and predicting survival.","Source":"STN","category":"HUMAN","training_data":"Evaluation Of Inflammation-Based Prognostic Scores In Patients Undergoing Hepatobiliary Resection For Perihilar Cholangiocarcinoma Background: Inflammation-based prognostic scores have prognostic value in several kinds of cancer. However, little is known about their value in perihilar cholangiocarcinoma. We evaluated whether inflammation-based prognostic scores are associated with survival of patients with perihilar cholangiocarcinoma. \r\n\r\n Methods: Inflammation-based scores (i.e., the modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio, platelet-lymphocyte ratio, and prognostic nutritional index) were retrospectively evaluated in 534 patients who underwent resection for perihilar cholangiocarcinoma. Blood samples obtained 1-3 days before surgery after jaundice had fully resolved with biliary drainage and after cholangitis had subsided were used to obtain the scores. \r\n\r\n Results: Of the four scores evaluated, the mGPS showed prognostic value, whereas the remaining three scores did not. Patients with an mGPS of 0 had significantly better survival than patients with an mGPS of 1 or 2 (41.9 % vs 26.3 % at 5 years, P < 0.001). An mGPS of 1 or 2 was significantly associated with a higher incidence of preoperative cholangitis, node metastasis, and distant metastasis (pM). Irrespective of the absence (n = 442) or presence (n = 92) of preoperative cholangitis, the survival of patients with an mGPS of 0 was significantly better than that of patients with an mGPS of 1 or 2. Multivariate analysis revealed that the mGPS, blood transfusion, histologic grade, curability (R status), lymph node metastasis, and distant metastasis were independent prognostic factors. \r\n\r\n Conclusions: As in other solid cancers, the mGPS is an independent prognostic factor in resected perihilar cholangiocarcinoma. This simple and inexpensive scoring system plays an important role in refining patient stratification and predicting survival. STN","prediction_labels":"HUMAN"},{"cleaned":"spock1 potential cancer prognostic marker promotes proliferation metastasis gallbladder cancer cells activating pi3k akt pathway background gallbladder cancer gbc leading cause cancer related death worldwide prognosis remains poor 5 year survival approximately 5 study analyzed involvement novel proteoglycan sparc osteonectin cwcv kazal like domains proteoglycan 1 spock1 tumor progression prognosis human gbc methods spock1 expression levels measured fresh samples stored specimens gbc adjacent nontumor tissues effect spock1 cell growth dna replication migration invasion explored cell counting kit 8 colony formation edu retention assay wound healing transwell migration assays flow cytometric analysis western blotting vivo tumorigenesis metastasis nude mice results spock1 mrna protein levels increased human gbc tissues compared nontumor tissues immunohistochemical analysis indicated spock1 levels increased tumors became metastatic compared significantly associated histological differentiation patients shorter overall survival periods knockdown spock1 expression lentivirus mediated shrna transduction resulted significant inhibition gbc cell growth colony formation dna replication invasion vitro knockdown cells also formed smaller xenografted tumors control gbc cells nude mice overexpression spock1 opposite effects addition spock1 promoted cancer cell migration epithelial mesenchymal transition regulating expression relevant genes found activation pi3k akt pathway involved oncogenic functions spock1 gbc conclusions spock1 activates pi3k akt signaling block apoptosis promote proliferation metastasis gbc cells vitro vivo levels spock1 increase progression human gbc spock1 acts oncogene may prognostic factor therapeutic target patients gbc stn","probabilities":0.9467213,"Title":"Spock1 As A Potential Cancer Prognostic Marker Promotes The Proliferation And Metastasis Of Gallbladder Cancer Cells By Activating The Pi3K/Akt Pathway","Abstract":"Background: Gallbladder cancer (GBC) is a leading cause of cancer-related death worldwide, and its prognosis remains poor, with 5-year survival of approximately 5%. In this study, we analyzed the involvement of a novel proteoglycan, Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1), in the tumor progression and prognosis of human GBC. \r\n\r\n Methods: SPOCK1 expression levels were measured in fresh samples and stored specimens of GBC and adjacent nontumor tissues. The effect of SPOCK1 on cell growth, DNA replication, migration and invasion were explored by Cell Counting Kit-8, colony formation, EdU retention assay, wound healing, and transwell migration assays, flow cytometric analysis, western blotting, and in vivo tumorigenesis and metastasis in nude mice. \r\n\r\n Results: SPOCK1 mRNA and protein levels were increased in human GBC tissues compared with those in nontumor tissues. Immunohistochemical analysis indicated that SPOCK1 levels were increased in tumors that became metastatic, compared with those that did not, which was significantly associated with histological differentiation and patients with shorter overall survival periods. Knockdown of SPOCK1 expression by lentivirus-mediated shRNA transduction resulted in significant inhibition of GBC cell growth, colony formation, DNA replication, and invasion in vitro. The knockdown cells also formed smaller xenografted tumors than control GBC cells in nude mice. Overexpression of SPOCK1 had the opposite effects. In addition, SPOCK1 promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of relevant genes. We found that activation of the PI3K/Akt pathway was involved in the oncogenic functions of SPOCK1 in GBC. \r\n\r\n Conclusions: SPOCK1 activates PI3K/Akt signaling to block apoptosis and promote proliferation and metastasis by GBC cells in vitro and in vivo. Levels of SPOCK1 increase with the progression of human GBC. SPOCK1 acts as an oncogene and may be a prognostic factor or therapeutic target for patients with GBC.","Source":"STN","category":"ANIMAL","training_data":"Spock1 As A Potential Cancer Prognostic Marker Promotes The Proliferation And Metastasis Of Gallbladder Cancer Cells By Activating The Pi3K/Akt Pathway Background: Gallbladder cancer (GBC) is a leading cause of cancer-related death worldwide, and its prognosis remains poor, with 5-year survival of approximately 5%. In this study, we analyzed the involvement of a novel proteoglycan, Sparc/osteonectin, cwcv, and kazal-like domains proteoglycan 1 (SPOCK1), in the tumor progression and prognosis of human GBC. \r\n\r\n Methods: SPOCK1 expression levels were measured in fresh samples and stored specimens of GBC and adjacent nontumor tissues. The effect of SPOCK1 on cell growth, DNA replication, migration and invasion were explored by Cell Counting Kit-8, colony formation, EdU retention assay, wound healing, and transwell migration assays, flow cytometric analysis, western blotting, and in vivo tumorigenesis and metastasis in nude mice. \r\n\r\n Results: SPOCK1 mRNA and protein levels were increased in human GBC tissues compared with those in nontumor tissues. Immunohistochemical analysis indicated that SPOCK1 levels were increased in tumors that became metastatic, compared with those that did not, which was significantly associated with histological differentiation and patients with shorter overall survival periods. Knockdown of SPOCK1 expression by lentivirus-mediated shRNA transduction resulted in significant inhibition of GBC cell growth, colony formation, DNA replication, and invasion in vitro. The knockdown cells also formed smaller xenografted tumors than control GBC cells in nude mice. Overexpression of SPOCK1 had the opposite effects. In addition, SPOCK1 promoted cancer cell migration and epithelial-mesenchymal transition by regulating the expression of relevant genes. We found that activation of the PI3K/Akt pathway was involved in the oncogenic functions of SPOCK1 in GBC. \r\n\r\n Conclusions: SPOCK1 activates PI3K/Akt signaling to block apoptosis and promote proliferation and metastasis by GBC cells in vitro and in vivo. Levels of SPOCK1 increase with the progression of human GBC. SPOCK1 acts as an oncogene and may be a prognostic factor or therapeutic target for patients with GBC. STN","prediction_labels":"ANIMAL"},{"cleaned":"gallbladder neuroendocrine carcinoma report 10 cases comparision clinicopathologic features gallbladder adenocarcinoma cases neuroendocrine carcinoma nec gallbladder gb nec reported data obtained 10 patients gb nec treated hospital january 2008 december 2012 retrospectively analyzed compared 377 patients gallbladder adenocarcinoma gb nec accounted 2 2 gallbladder cancers patients 8 females 2 males 59 0 10 0 years old four patients presented mixed adenocarcinoma six pure nec immunohistochemical examinations showed positive rate 100 cga nse ck positive rates syn ema cd56 88 9 87 5 75 respectively tnm grades ii iva ivb found 1 2 7 patients respectively gb nec patients showed significantly higher n2 lymphatic metastasis rates gallbladder adenocarcinoma patients 70 0 vs 34 0 p 0 05 two patients treated radical resection remaining 8 palliative operation 1 2 3 year survival rates 20 10 0 respectively median survival time 3 0 m 1 2 3 5 year survival rates gallbladder adenocarcinoma patients 38 0 31 0 30 1 28 4 respectively median survival time 6 0 m difference statistically significant p 0 038 results demonstrate gb nec mainly found aged females shows high malignancy prognosis poorer gallbladder adenocarcinoma surgical resection combined tace radiotherapy chemotherapy increase patient survival pubmed","probabilities":0.9799733,"Title":"Gallbladder neuroendocrine carcinoma: report of 10 cases and comparision of clinicopathologic features with gallbladder adenocarcinoma","Abstract":"Few cases of neuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) have been reported. Data obtained from the 10 patients with GB-NEC treated in our hospital between January 2008 and December 2012 were retrospectively analyzed and compared with those of 377 patients with gallbladder adenocarcinoma. GB-NEC accounted for 2.2% of all gallbladder cancers. The patients (8 females and 2 males) were 59.0 ± 10.0 years old. Four patients presented mixed adenocarcinoma, while six had pure NEC. Immunohistochemical examinations showed a positive rate of 100% for CgA, NSE, and CK; the positive rates for Syn, EMA, and CD56 were 88.9, 87.5, and 75%, respectively. TNM grades II, IVA, and IVB were found in 1, 2, and 7 patients, respectively. GB-NEC patients showed significantly higher N2 lymphatic metastasis rates than gallbladder adenocarcinoma patients (70.0 vs. 34.0%; P < 0.05). Two patients were treated with radical resection and the remaining 8 with palliative operation. The 1-, 2-, and 3-year survival rates were 20, 10, and 0%, respectively (median survival time, 3.0 m); the 1-, 2-, 3-, and 5-year survival rates for all gallbladder adenocarcinoma patients were 38.0, 31.0, 30.1, and 28.4%, respectively (median survival time, 6.0 m), the difference was statistically significant (P = 0.038). The results demonstrate that GB-NEC was mainly found in aged females and shows high malignancy. Its prognosis is poorer than that of gallbladder adenocarcinoma, and surgical resection combined with TACE, radiotherapy, and chemotherapy could increase patient survival.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder neuroendocrine carcinoma: report of 10 cases and comparision of clinicopathologic features with gallbladder adenocarcinoma Few cases of neuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) have been reported. Data obtained from the 10 patients with GB-NEC treated in our hospital between January 2008 and December 2012 were retrospectively analyzed and compared with those of 377 patients with gallbladder adenocarcinoma. GB-NEC accounted for 2.2% of all gallbladder cancers. The patients (8 females and 2 males) were 59.0 ± 10.0 years old. Four patients presented mixed adenocarcinoma, while six had pure NEC. Immunohistochemical examinations showed a positive rate of 100% for CgA, NSE, and CK; the positive rates for Syn, EMA, and CD56 were 88.9, 87.5, and 75%, respectively. TNM grades II, IVA, and IVB were found in 1, 2, and 7 patients, respectively. GB-NEC patients showed significantly higher N2 lymphatic metastasis rates than gallbladder adenocarcinoma patients (70.0 vs. 34.0%; P < 0.05). Two patients were treated with radical resection and the remaining 8 with palliative operation. The 1-, 2-, and 3-year survival rates were 20, 10, and 0%, respectively (median survival time, 3.0 m); the 1-, 2-, 3-, and 5-year survival rates for all gallbladder adenocarcinoma patients were 38.0, 31.0, 30.1, and 28.4%, respectively (median survival time, 6.0 m), the difference was statistically significant (P = 0.038). The results demonstrate that GB-NEC was mainly found in aged females and shows high malignancy. Its prognosis is poorer than that of gallbladder adenocarcinoma, and surgical resection combined with TACE, radiotherapy, and chemotherapy could increase patient survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"beclin 1 deficiency correlated lymph node metastasis predicts distinct outcome intrahepatic extrahepatic cholangiocarcinoma autophagy tumor suppressive well promotive regulation tumorigenesis disease progression accordingly prognostic significance autophagy key regulator beclin 1 varied among different tumors detected clinicopathological prognostic effect beclin 1 subtypes intrahepatic cholangiocarcinoma icc extrahepatic cholangiocarcinoma ecc beclin 1 expression level detected immunohistochemistry staining 106 icc 74 ecc patients found beclin 1 lowly expressed 126 70 cholangiocarcinoma patients consist 72 icc 54 ecc moreover cholangiocarcinoma patients lymph node metastasis n1 lower beclin 1 level n0 subgroup p 0 012 however detect correlations beclin 1 clinicopathological features including tumor subtypes vascular invasion hbv infection liver cirrhosis cholecystolithiasis tnm stage survival analysis showed compared high expression subset beclin 1 low expression correlated poorer 3 year progression free survival pfs 69 1 vs 46 8 p 041 cholangiocarcinoma importantly stratified univariate multivariate analysis confirmed beclin 1 lowly expressed icc inferior pfs well overall survival ecc particularly beclin 1 highly expressed ecc patients thus study demonstrated beclin 1low expression correlated lymph node metastasis might negative prognostic biomarker cholangiocarcinoma combined beclin 1 level anatomical location might lead refined prognosis subtypes icc ecc stn","probabilities":0.9799733,"Title":"Beclin 1 Deficiency Correlated With Lymph Node Metastasis Predicts A Distinct Outcome In Intrahepatic And Extrahepatic Cholangiocarcinoma","Abstract":"Autophagy can be tumor suppressive as well as promotive in regulation of tumorigenesis and disease progression. Accordingly, the prognostic significance of autophagy key regulator Beclin 1 was varied among different tumors. Here, we detected the clinicopathological and prognostic effect of Beclin 1 in the subtypes of intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Beclin 1 expression level was detected by immunohistochemistry staining in 106 ICC and 74 ECC patients. We found that Beclin 1 was lowly expressed in 126 (70%) cholangiocarcinoma patients, consist of 72 ICC and 54 ECC. Moreover, the cholangiocarcinoma patients with lymph node metastasis (N1) had a lower Beclin 1 level than that of N0 subgroup (P=0.012). However, we did not detect any correlations between Beclin 1 and other clinicopathological features, including tumor subtypes, vascular invasion, HBV infection, liver cirrhosis, cholecystolithiasis and TNM stage. Survival analysis showed that, compared with the high expression subset, Beclin 1 low expression was correlated with a poorer 3-year progression-free survival (PFS, 69.1% VS 46.8%, P=041) for cholangiocarcinoma. Importantly, our stratified univariate and multivariate analysis confirmed that Beclin 1 lowly expressed ICC had an inferior PFS as well as overall survival than ECC, particularly than that of Beclin 1 highly expressed ECC patients. Thus, our study demonstrated that Beclin 1low expression, correlated with lymph node metastasis, and might be a negative prognostic biomarker for cholangiocarcinoma. Combined Beclin 1 level with the anatomical location might lead to refined prognosis for the subtypes of ICC and ECC.","Source":"STN","category":"HUMAN","training_data":"Beclin 1 Deficiency Correlated With Lymph Node Metastasis Predicts A Distinct Outcome In Intrahepatic And Extrahepatic Cholangiocarcinoma Autophagy can be tumor suppressive as well as promotive in regulation of tumorigenesis and disease progression. Accordingly, the prognostic significance of autophagy key regulator Beclin 1 was varied among different tumors. Here, we detected the clinicopathological and prognostic effect of Beclin 1 in the subtypes of intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). Beclin 1 expression level was detected by immunohistochemistry staining in 106 ICC and 74 ECC patients. We found that Beclin 1 was lowly expressed in 126 (70%) cholangiocarcinoma patients, consist of 72 ICC and 54 ECC. Moreover, the cholangiocarcinoma patients with lymph node metastasis (N1) had a lower Beclin 1 level than that of N0 subgroup (P=0.012). However, we did not detect any correlations between Beclin 1 and other clinicopathological features, including tumor subtypes, vascular invasion, HBV infection, liver cirrhosis, cholecystolithiasis and TNM stage. Survival analysis showed that, compared with the high expression subset, Beclin 1 low expression was correlated with a poorer 3-year progression-free survival (PFS, 69.1% VS 46.8%, P=041) for cholangiocarcinoma. Importantly, our stratified univariate and multivariate analysis confirmed that Beclin 1 lowly expressed ICC had an inferior PFS as well as overall survival than ECC, particularly than that of Beclin 1 highly expressed ECC patients. Thus, our study demonstrated that Beclin 1low expression, correlated with lymph node metastasis, and might be a negative prognostic biomarker for cholangiocarcinoma. Combined Beclin 1 level with the anatomical location might lead to refined prognosis for the subtypes of ICC and ECC. STN","prediction_labels":"HUMAN"},{"cleaned":"patients gall bladder cancer likely survive long abstract available google scholar","probabilities":0.9799733,"Title":"Which Patients With Gall Bladder Cancer Are Likely To Survive Long?","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Which Patients With Gall Bladder Cancer Are Likely To Survive Long? Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"geographical temporal variation incidence mortality hepato pancreato biliary primary malignancies 1990 2017 background hepatic pancreas biliary hpb cancers pose serious challenges global health care systems malignancies demonstrate great geographical variations shifting trends time aim present study determine recent trends incidence prevalence mortality primary hpb malignancies guide development effective strategies prevention screening treatment methods global burden disease gbd dataset 1990 2017 interrogated end point variables age sex year geography epidemiologic data modeled dismod mr 2 1 bayesian meta regression tool pools data points different sources adjusts known sources variability global burden disease data extracted 284 country year 976 subnational year combinations 27 countries north america latin america europe india new zealand results although global incidence primary hpb malignancies increased 1 43 1990 2017 1 400 739 cases incidence extrahepatic biliary gallbladder malignancies decreased 0 32 210 878 cases period significant variability incidence prevalence mortality hpb cancers sociodemographic index sdi well geography largest incidence increase primary liver pancreas cancers seen high income asia pacific group followed high income north america western europe groups highest incidences prevalence extrahepatic biliary gallbladder malignancies observed asia pacific southern latin american andean latin american regions general mortality rates hpb malignancies larger low sdi compared high sdi group geographical regions conclusions global incidence prevalence primary liver pancreatic malignancies continue increase great geographical variation mortality trends mirror incidence although global incidence prevalence extrahepatic biliary gallbladder malignancies decreased mortality rate significantly changed results article assist local regional authorities policy development improve health care access screening early detection treatment hpb malignancies pubmed","probabilities":0.9799733,"Title":"Geographical and Temporal Variation in the Incidence and Mortality of Hepato-Pancreato-Biliary Primary Malignancies:1990-2017","Abstract":"BACKGROUND: Hepatic, pancreas, and biliary (HPB) cancers pose serious challenges to global health care systems. These malignancies demonstrate great geographical variations with shifting trends over time. The aim of the present study was to determine the recent trends in incidence, prevalence, and mortality of primary HPB malignancies to guide the further development of effective strategies for prevention, screening, and treatment. METHODS: The Global Burden of Disease (GBD) dataset 1990-2017 was interrogated for end point variables by age, sex, year, and geography. Epidemiologic data were modeled in DisMod-MR 2.1, a Bayesian meta-regression tool that pools data points from different sources and adjusts for known sources of variability. Global Burden of Disease data were extracted from 284 country-year, and 976 subnational-year combinations from 27 countries in North America, Latin America, Europe, India, and New Zealand. RESULTS: Although the global incidence of primary HPB malignancies increased by 1.43% from 1990 to 2017 (1,400,739 cases), the incidence of extrahepatic biliary and gallbladder malignancies decreased by -0.32% (210,878 cases) over the same period. There was significant variability in the incidence, prevalence, and mortality of HPB cancers by the sociodemographic index (SDI), as well as by geography. The largest incidence increase of primary liver and pancreas cancers was seen in the high-income Asia-Pacific group, followed by the high-income North America and Western Europe groups. The highest incidences and prevalence of extrahepatic biliary and gallbladder malignancies were observed in Asia-Pacific, Southern Latin American, and Andean Latin American regions. In general, mortality rates of HPB malignancies were larger in the low SDI when compared with the high SDI group in all geographical regions. CONCLUSIONS: The global incidence and prevalence of primary liver and pancreatic malignancies continue to increase with great geographical variation. The mortality trends mirror those of the incidence. Although the global incidence and prevalence of extrahepatic biliary and gallbladder malignancies has decreased, the mortality rate has not significantly changed. The results of this article can assist local and regional authorities in policy development to improve health care access for screening, early detection, and treatment of HPB malignancies.","Source":"PubMed","category":"HUMAN","training_data":"Geographical and Temporal Variation in the Incidence and Mortality of Hepato-Pancreato-Biliary Primary Malignancies:1990-2017 BACKGROUND: Hepatic, pancreas, and biliary (HPB) cancers pose serious challenges to global health care systems. These malignancies demonstrate great geographical variations with shifting trends over time. The aim of the present study was to determine the recent trends in incidence, prevalence, and mortality of primary HPB malignancies to guide the further development of effective strategies for prevention, screening, and treatment. METHODS: The Global Burden of Disease (GBD) dataset 1990-2017 was interrogated for end point variables by age, sex, year, and geography. Epidemiologic data were modeled in DisMod-MR 2.1, a Bayesian meta-regression tool that pools data points from different sources and adjusts for known sources of variability. Global Burden of Disease data were extracted from 284 country-year, and 976 subnational-year combinations from 27 countries in North America, Latin America, Europe, India, and New Zealand. RESULTS: Although the global incidence of primary HPB malignancies increased by 1.43% from 1990 to 2017 (1,400,739 cases), the incidence of extrahepatic biliary and gallbladder malignancies decreased by -0.32% (210,878 cases) over the same period. There was significant variability in the incidence, prevalence, and mortality of HPB cancers by the sociodemographic index (SDI), as well as by geography. The largest incidence increase of primary liver and pancreas cancers was seen in the high-income Asia-Pacific group, followed by the high-income North America and Western Europe groups. The highest incidences and prevalence of extrahepatic biliary and gallbladder malignancies were observed in Asia-Pacific, Southern Latin American, and Andean Latin American regions. In general, mortality rates of HPB malignancies were larger in the low SDI when compared with the high SDI group in all geographical regions. CONCLUSIONS: The global incidence and prevalence of primary liver and pancreatic malignancies continue to increase with great geographical variation. The mortality trends mirror those of the incidence. Although the global incidence and prevalence of extrahepatic biliary and gallbladder malignancies has decreased, the mortality rate has not significantly changed. The results of this article can assist local and regional authorities in policy development to improve health care access for screening, early detection, and treatment of HPB malignancies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"improving understanding surgical oncology workforce objective study characterizes surgical oncology workforce baseline future workforce projections background measuring capacity surgical oncology workforce difficult due wide variety surgeons contribute surgical cancer care hypothesize bulk surgical oncology care provided general surgeons methods using medicare claims data linked north carolina central cancer registry patients 65 years older diagnosis incident cancer bladder breast colon rectum esophagus gallbladder kidney liver lung skin melanoma ovary pancreas prostate small bowel stomach uterus 2005 underwent extirpative procedure cancer identified proportion procedures performed different types providers examined results total 7759 patients underwent 16 734 extirpative surgical procedures excluding procedures gynecologic urologic malignancies proportion procedures performed general surgeons surgical oncologists 48 12 respectively patients treated general surgeons likely older female minority areas high poverty tumor type travel distances shorter patients treated general surgeons treated specialists conclusions workforce projections must account significant overlap scope services delivered providers different specialties large contribution general surgeons cancer care efforts improve quality cancer care need move beyond centralization focus educating surgeons providing bulk oncology care pubmed","probabilities":0.9799733,"Title":"Improving our understanding of the surgical oncology workforce","Abstract":"OBJECTIVE: This study characterizes the surgical oncology workforce as a baseline for future workforce projections. BACKGROUND: Measuring the capacity of the surgical oncology workforce is difficult due to the wide variety of surgeons who contribute to surgical cancer care. We hypothesize that the bulk of surgical oncology care is provided by general surgeons. METHODS: Using Medicare claims data linked to the North Carolina Central Cancer Registry, all patients 65 years or older who had a diagnosis of incident cancer of the bladder, breast, colon/rectum, esophagus, gallbladder, kidney, liver, lung, skin (melanoma-only), ovary, pancreas, prostate, small bowel, stomach, or uterus in 2005 and who underwent an extirpative procedure for cancer were identified. The proportion of procedures performed by different types of providers was examined. RESULTS: A total of 7759 patients underwent 16,734 extirpative surgical procedures. Excluding procedures for gynecologic/urologic malignancies, the proportion of procedures performed by general surgeons and surgical oncologists was 48% and 12%, respectively. Patients treated by general surgeons were more likely to be older, female, minority, and from areas of high poverty. For each tumor type, travel distances were shorter for patients treated by general surgeons than those treated by specialists. CONCLUSIONS: Workforce projections must account for the significant overlap in the scope of services delivered by providers of different specialties and for the large contribution of general surgeons to cancer care. Efforts to improve the quality of cancer care need to move beyond centralization and focus on educating the surgeons who are providing the bulk of oncology care.","Source":"PubMed","category":"HUMAN","training_data":"Improving our understanding of the surgical oncology workforce OBJECTIVE: This study characterizes the surgical oncology workforce as a baseline for future workforce projections. BACKGROUND: Measuring the capacity of the surgical oncology workforce is difficult due to the wide variety of surgeons who contribute to surgical cancer care. We hypothesize that the bulk of surgical oncology care is provided by general surgeons. METHODS: Using Medicare claims data linked to the North Carolina Central Cancer Registry, all patients 65 years or older who had a diagnosis of incident cancer of the bladder, breast, colon/rectum, esophagus, gallbladder, kidney, liver, lung, skin (melanoma-only), ovary, pancreas, prostate, small bowel, stomach, or uterus in 2005 and who underwent an extirpative procedure for cancer were identified. The proportion of procedures performed by different types of providers was examined. RESULTS: A total of 7759 patients underwent 16,734 extirpative surgical procedures. Excluding procedures for gynecologic/urologic malignancies, the proportion of procedures performed by general surgeons and surgical oncologists was 48% and 12%, respectively. Patients treated by general surgeons were more likely to be older, female, minority, and from areas of high poverty. For each tumor type, travel distances were shorter for patients treated by general surgeons than those treated by specialists. CONCLUSIONS: Workforce projections must account for the significant overlap in the scope of services delivered by providers of different specialties and for the large contribution of general surgeons to cancer care. Efforts to improve the quality of cancer care need to move beyond centralization and focus on educating the surgeons who are providing the bulk of oncology care. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognosis incidental gallbladder carcinoma influenced primary access technique analysis 837 incidental gallbladder carcinomas german registry background use laparoscopic approach lc gallbladder carcinoma incidental gallbladder carcinomas igbc remains controversial however recent studies suggest lc adverse effects relative open approach definitive conclusion regarding safety lc based data large patient cohort needed methods draw definite conclusion safety lc igbc data 837 patients igbc registered german registry gr analyzed results 837 patients 492 underwent lc 200 underwent open surgery oc 142 initially underwent lc approach converted oc 5 year survival rates three groups indicated lc associated significantly better survival lc associated poorer prognosis patients t1 t2 t3 stage disease patients underwent immediate radical re resection irr n 330 lc associated significant survival benefit 490 patients undergo irr lc comparable oc terms overall recurrence rates rate accidental intraoperative perforation conclusions gr data relate large homogenous patient cohort showed potential influencing factors e g irr eliminated primary access technique effect prognosis stage adjusted therapy always performed irrespective primary access technique pubmed","probabilities":0.9799733,"Title":"Prognosis of incidental gallbladder carcinoma is not influenced by the primary access technique: analysis of 837 incidental gallbladder carcinomas in the German Registry","Abstract":"BACKGROUND: The use of the laparoscopic approach (LC) for gallbladder carcinoma and incidental gallbladder carcinomas (IGBC) remains controversial. However, recent studies suggest that LC has no adverse effects relative to the open approach. A definitive conclusion regarding the safety of LC that is based on data from a large patient cohort is needed. METHODS: To draw a definite conclusion about the safety of LC in IGBC, data from the 837 patients with IGBC [registered in the German Registry (GR)] were analyzed. RESULTS: Of the 837 patients, 492 underwent LC, 200 underwent open surgery (OC), and 142 initially underwent LC, but the approach was converted to OC. The 5-year survival rates of the three groups indicated that LC was associated with significantly better survival. LC was not associated with a poorer prognosis in patients with T1, T2, or T3 stage disease or in patients who underwent immediate radical re-resection (IRR; n = 330). LC was associated with a significant survival benefit in the 490 patients who did not undergo IRR. LC was comparable with OC in terms of overall recurrence rates and the rate of accidental intraoperative perforation. CONCLUSIONS: The GR data, which relate to a large homogenous patient cohort, showed that when other potential influencing factors, e.g., IRR were eliminated, the primary access technique had no effect on prognosis. Stage-adjusted therapy should always be performed irrespective of the primary access technique.","Source":"PubMed","category":"HUMAN","training_data":"Prognosis of incidental gallbladder carcinoma is not influenced by the primary access technique: analysis of 837 incidental gallbladder carcinomas in the German Registry BACKGROUND: The use of the laparoscopic approach (LC) for gallbladder carcinoma and incidental gallbladder carcinomas (IGBC) remains controversial. However, recent studies suggest that LC has no adverse effects relative to the open approach. A definitive conclusion regarding the safety of LC that is based on data from a large patient cohort is needed. METHODS: To draw a definite conclusion about the safety of LC in IGBC, data from the 837 patients with IGBC [registered in the German Registry (GR)] were analyzed. RESULTS: Of the 837 patients, 492 underwent LC, 200 underwent open surgery (OC), and 142 initially underwent LC, but the approach was converted to OC. The 5-year survival rates of the three groups indicated that LC was associated with significantly better survival. LC was not associated with a poorer prognosis in patients with T1, T2, or T3 stage disease or in patients who underwent immediate radical re-resection (IRR; n = 330). LC was associated with a significant survival benefit in the 490 patients who did not undergo IRR. LC was comparable with OC in terms of overall recurrence rates and the rate of accidental intraoperative perforation. CONCLUSIONS: The GR data, which relate to a large homogenous patient cohort, showed that when other potential influencing factors, e.g., IRR were eliminated, the primary access technique had no effect on prognosis. Stage-adjusted therapy should always be performed irrespective of the primary access technique. PubMed","prediction_labels":"HUMAN"},{"cleaned":"major hepatectomy bismuth types ii hilar cholangiocarcinoma background historically hilar bile duct resection hbdr regarded choice treatment bismuth types ii hilar cholangiocarcinoma hcca present study aimed evaluate advantages major liver resection mlr treatment patients bismuth types ii hcca compared hbdr materials methods january 2005 september 2012 total 52 patients bismuth types ii hcca underwent hbdr alone mlr included retrospective analysis intraoperative outcomes postoperative complications oncological outcomes including recurrence overall disease free survival rate compared results mlr group significantly higher curative resection rates compared hbdr group 95 versus 62 5 p 0 021 lower tumor recurrence 28 versus 63 p 0 049 albeit longer operating time 395 5 112 7 versus 270 9 98 8 p 0 001 higher blood transfusion requirements 70 versus 16 p 0 001 mlr resulted significantly higher overall postoperative morbidity 70 versus 34 4 p 0 012 compared hbdr alone restricted r0 resections procedures mlr significantly increased overall postoperative survival rate compared hbdr group p 0 016 overall survival rate 1 3 y 68 4 60 8 mlr group 59 6 21 9 hbdr group respectively also disease free survival rate significantly higher patients underwent mlr compared underwent hbdr 53 2 versus 0 3 y p 0 005 conclusions study shown mlr results higher curative resections fewer recurrences increased postoperative survival rate bismuth types ii hcca compared hbdr alone however need well designed multicenter studies undertaken better inform decision standard treatment bismuth types ii hcca pubmed","probabilities":0.9799733,"Title":"Major hepatectomy in Bismuth types I and II hilar cholangiocarcinoma","Abstract":"BACKGROUND: Historically, hilar bile duct resection (HBDR) has been regarded as the choice of treatment for Bismuth types I and II hilar cholangiocarcinoma (HCCA). The present study aimed to evaluate the advantages of major liver resection (MLR) in the treatment of patients with Bismuth types I and II HCCA when compared with HBDR. MATERIALS AND METHODS: Between January 2005 and September 2012, in total, 52 patients with Bismuth types I and II HCCA who underwent HBDR alone or MLR were included for retrospective analysis. The intraoperative outcomes, postoperative complications, and oncological outcomes including recurrence and overall or disease-free survival rate were compared. RESULTS: The MLR group had significantly higher curative resection rates compared with the HBDR group (95% versus 62.5%, P = 0.021) and lower tumor recurrence (28% versus 63%, P = 0.049), albeit with longer operating time (395.5 ± 112.7 versus 270.9 ± 98.8, P < 0.001), and higher blood transfusion requirements (70% versus 16%, P < 0.001). MLR resulted in significantly higher overall postoperative morbidity (70% versus 34.4%, P = 0.012), compared with HBDR alone. When restricted to R0 resections for all the procedures, MLR significantly increased the overall postoperative survival rate compared with the HBDR group (P = 0.016); the overall survival rate at 1, 3 y was 68.4% and 60.8% for MLR group and 59.6% and 21.9% for HBDR group, respectively. Also, the disease-free survival rate was significantly higher in patients who underwent MLR, as compared with those who underwent HBDR (53.2% versus 0% at 3 y, P = 0.005). CONCLUSIONS: Our study has shown that MLR results in higher curative resections, fewer recurrences, and increased postoperative survival rate for Bismuth types I and II HCCA as compared with HBDR alone. However, there is a need for well-designed, multicenter studies to be undertaken to better inform a decision on the standard treatment for Bismuth types I and II HCCA.","Source":"PubMed","category":"HUMAN","training_data":"Major hepatectomy in Bismuth types I and II hilar cholangiocarcinoma BACKGROUND: Historically, hilar bile duct resection (HBDR) has been regarded as the choice of treatment for Bismuth types I and II hilar cholangiocarcinoma (HCCA). The present study aimed to evaluate the advantages of major liver resection (MLR) in the treatment of patients with Bismuth types I and II HCCA when compared with HBDR. MATERIALS AND METHODS: Between January 2005 and September 2012, in total, 52 patients with Bismuth types I and II HCCA who underwent HBDR alone or MLR were included for retrospective analysis. The intraoperative outcomes, postoperative complications, and oncological outcomes including recurrence and overall or disease-free survival rate were compared. RESULTS: The MLR group had significantly higher curative resection rates compared with the HBDR group (95% versus 62.5%, P = 0.021) and lower tumor recurrence (28% versus 63%, P = 0.049), albeit with longer operating time (395.5 ± 112.7 versus 270.9 ± 98.8, P < 0.001), and higher blood transfusion requirements (70% versus 16%, P < 0.001). MLR resulted in significantly higher overall postoperative morbidity (70% versus 34.4%, P = 0.012), compared with HBDR alone. When restricted to R0 resections for all the procedures, MLR significantly increased the overall postoperative survival rate compared with the HBDR group (P = 0.016); the overall survival rate at 1, 3 y was 68.4% and 60.8% for MLR group and 59.6% and 21.9% for HBDR group, respectively. Also, the disease-free survival rate was significantly higher in patients who underwent MLR, as compared with those who underwent HBDR (53.2% versus 0% at 3 y, P = 0.005). CONCLUSIONS: Our study has shown that MLR results in higher curative resections, fewer recurrences, and increased postoperative survival rate for Bismuth types I and II HCCA as compared with HBDR alone. However, there is a need for well-designed, multicenter studies to be undertaken to better inform a decision on the standard treatment for Bismuth types I and II HCCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"readmission liver resection intrahepatic cholangiocarcinoma multi institutional analysis background objective current study define incidence 30 day readmission hepatic resection intrahepatic cholangiocarcinoma icc particular sought identify risk factors associated higher risk readmission among patients undergoing resection icc methods patients underwent hepatic resection icc 12 major hepatobiliary centers usa europe australia asia 1990 2013 identified thirty day readmission clinicopathologic characteristics associated higher risk readmission examined results among 602 patients 401 68 3 patients underwent major hepatectomy 256 43 3 experienced least one post operative complication overall 30 day readmission 7 8 n 47 risk factors associated readmission included pre operative jaundice odds ratio 2 45 presence major complication 3 38 fact 95 7 readmitted patients experienced post operative complication versus 38 8 non readmitted patients p 0 001 among patients readmitted repeat hospitalization associated median los 6 5 days interquartile range iqr 4 0 11 5 one patient died readmission conclusions readmission hepatic resection icc occurred 1 13 patients patients pre operative jaundice experienced complication threefold higher risk readmitted pubmed","probabilities":0.9799733,"Title":"Readmission After Liver Resection for Intrahepatic Cholangiocarcinoma: a Multi-Institutional Analysis","Abstract":"BACKGROUND: The objective of the current study was to define the incidence of 30-day readmission after hepatic resection for intrahepatic cholangiocarcinoma (ICC). In particular, we sought to identify risk factors associated with a higher risk of readmission among patients undergoing resection for ICC. METHODS: Patients who underwent hepatic resection for ICC at 12 major hepatobiliary centers in the USA, Europe, Australia, and Asia between 1990 and 2013 were identified. Thirty-day readmission and clinicopathologic characteristics associated with higher risk of readmission were examined. RESULTS: Among 602 patients, 401 (68.3%) patients underwent a major hepatectomy and 256 (43.3%) experienced at least one post-operative complication. Overall 30-day readmission was 7.8% (n = 47). Risk factors associated with readmission included pre-operative jaundice (odds ratio (OR) 2.45) and the presence of a major complication (OR 3.38). In fact, 95.7% of readmitted patients had experienced a post-operative complication versus only 38.8% of non-readmitted patients (P < 0.001). Among patients who were readmitted, repeat hospitalization was associated with a median LOS of 6.5 days (interquartile range (IQR) 4.0-11.5) and one patient died during readmission. CONCLUSIONS: Readmission after hepatic resection for ICC occurred in 1 in 13 patients. Patients with pre-operative jaundice and those who experienced a complication had over a threefold higher risk of being readmitted.","Source":"PubMed","category":"HUMAN","training_data":"Readmission After Liver Resection for Intrahepatic Cholangiocarcinoma: a Multi-Institutional Analysis BACKGROUND: The objective of the current study was to define the incidence of 30-day readmission after hepatic resection for intrahepatic cholangiocarcinoma (ICC). In particular, we sought to identify risk factors associated with a higher risk of readmission among patients undergoing resection for ICC. METHODS: Patients who underwent hepatic resection for ICC at 12 major hepatobiliary centers in the USA, Europe, Australia, and Asia between 1990 and 2013 were identified. Thirty-day readmission and clinicopathologic characteristics associated with higher risk of readmission were examined. RESULTS: Among 602 patients, 401 (68.3%) patients underwent a major hepatectomy and 256 (43.3%) experienced at least one post-operative complication. Overall 30-day readmission was 7.8% (n = 47). Risk factors associated with readmission included pre-operative jaundice (odds ratio (OR) 2.45) and the presence of a major complication (OR 3.38). In fact, 95.7% of readmitted patients had experienced a post-operative complication versus only 38.8% of non-readmitted patients (P < 0.001). Among patients who were readmitted, repeat hospitalization was associated with a median LOS of 6.5 days (interquartile range (IQR) 4.0-11.5) and one patient died during readmission. CONCLUSIONS: Readmission after hepatic resection for ICC occurred in 1 in 13 patients. Patients with pre-operative jaundice and those who experienced a complication had over a threefold higher risk of being readmitted. PubMed","prediction_labels":"HUMAN"},{"cleaned":"recurrent pyogenic cholangitis independent poor prognostic indicator resectable intrahepatic cholangiocarcinoma propensity score matched analysis background recurrent pyogenic cholangitis rpc known risk factor intrahepatic cholangiocarcinoma icc whether represents poor prognostic factor remains controversial aim study investigate post hepatectomy oncological outcomes patients icc coexisting rpc method retrospective analysis propensity score matching psm performed comparison icc patient without rpc results 143 patients icc median follow 21 months rpc diagnosed 18 patients time rpc diagnosis icc diagnosis 137 47 481 months 3 year disease free dfs overall survival whole population 34 43 respectively preoperative child score elevated carcinoembryonic antigen presence microvascular invasion multiple tumours presence postoperative complications rpc independent factors dfs os psm 60 icc patients rpc compared 20 icc patients rpc patients rpc significantly worse median dfs 10 vs 23 months p 0 020 os 15 vs 45 months p 0 004 compared patients without rpc conclusion rpc represents poor prognostic factor affecting outcomes hepatectomy patients icc pubmed","probabilities":0.9799733,"Title":"Recurrent pyogenic cholangitis - an independent poor prognostic indicator for resectable intrahepatic cholangiocarcinoma: A propensity score matched analysis","Abstract":"BACKGROUND: Recurrent pyogenic cholangitis (RPC) is a known risk factor for intrahepatic cholangiocarcinoma (ICC), whether it represents a poor prognostic factor remains controversial. The aim of this study was to investigate the post-hepatectomy oncological outcomes of patients with ICC and coexisting RPC. METHOD: A retrospective analysis with propensity score matching (PSM) was performed for comparison between ICC patient with and without RPC. RESULTS: There were 143 patients with ICC with a median follow-up of 21 months. RPC was diagnosed in 18% of patients. The time from RPC diagnosis to ICC diagnosis was 137(47-481) months. The 3-year disease-free (DFS) and overall survival for the whole population was 34% and 43% respectively. Preoperative child score, elevated carcinoembryonic antigen, presence of microvascular invasion, multiple tumours, presence of postoperative complications and RPC were independent factors for DFS and OS. After PSM, 60 ICC patients who did not have RPC were compared with 20 ICC patients with RPC. Patients with RPC had significantly worse median DFS (10 vs 23 months, P = 0.020) and OS (15 vs 45 months, P = 0.004) when compared to the patients without RPC. CONCLUSION: RPC represents a poor prognostic factor affecting outcomes after hepatectomy for patients with ICC.","Source":"PubMed","category":"HUMAN","training_data":"Recurrent pyogenic cholangitis - an independent poor prognostic indicator for resectable intrahepatic cholangiocarcinoma: A propensity score matched analysis BACKGROUND: Recurrent pyogenic cholangitis (RPC) is a known risk factor for intrahepatic cholangiocarcinoma (ICC), whether it represents a poor prognostic factor remains controversial. The aim of this study was to investigate the post-hepatectomy oncological outcomes of patients with ICC and coexisting RPC. METHOD: A retrospective analysis with propensity score matching (PSM) was performed for comparison between ICC patient with and without RPC. RESULTS: There were 143 patients with ICC with a median follow-up of 21 months. RPC was diagnosed in 18% of patients. The time from RPC diagnosis to ICC diagnosis was 137(47-481) months. The 3-year disease-free (DFS) and overall survival for the whole population was 34% and 43% respectively. Preoperative child score, elevated carcinoembryonic antigen, presence of microvascular invasion, multiple tumours, presence of postoperative complications and RPC were independent factors for DFS and OS. After PSM, 60 ICC patients who did not have RPC were compared with 20 ICC patients with RPC. Patients with RPC had significantly worse median DFS (10 vs 23 months, P = 0.020) and OS (15 vs 45 months, P = 0.004) when compared to the patients without RPC. CONCLUSION: RPC represents a poor prognostic factor affecting outcomes after hepatectomy for patients with ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatitis b risk non hepatocellular carcinoma malignancy chronic hepatitis b infection chb known risk factor malignancy unlike hepatocellular carcinoma hcc less known risk non hcc malignancy however epidemiology pathologic evidence suggests strong association non hodgkin lymphoma chb data regarding risk malignancies pancreatic adenocarcinoma intrahepatic cholangiocarcinoma mixed surveillance appropriate treatment infection malignancy patients essential study associations needed may bring new insights pathogenesis treatment diseases pubmed","probabilities":0.9799733,"Title":"Hepatitis B and Risk of Non-Hepatocellular Carcinoma Malignancy","Abstract":"Chronic hepatitis B infection (CHB) is a known risk factor for malignancy. Unlike hepatocellular carcinoma (HCC), less is known about the risk of non-HCC malignancy. However, epidemiology and pathologic evidence suggests a strong association between non-Hodgkin lymphoma and CHB. Data regarding the risk of other malignancies, such as pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma, are mixed. Surveillance and appropriate treatment of infection and malignancy in these patients is essential. Further study of these associations is needed and may bring new insights in the pathogenesis and treatment of these diseases.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis B and Risk of Non-Hepatocellular Carcinoma Malignancy Chronic hepatitis B infection (CHB) is a known risk factor for malignancy. Unlike hepatocellular carcinoma (HCC), less is known about the risk of non-HCC malignancy. However, epidemiology and pathologic evidence suggests a strong association between non-Hodgkin lymphoma and CHB. Data regarding the risk of other malignancies, such as pancreatic adenocarcinoma and intrahepatic cholangiocarcinoma, are mixed. Surveillance and appropriate treatment of infection and malignancy in these patients is essential. Further study of these associations is needed and may bring new insights in the pathogenesis and treatment of these diseases. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact toll like receptor 4 polymorphisms risk cancer toll like receptor 4 tlr4 one key immune system effectors playing main role recognition viruses bacteria dysregulation tlr4 signaling owing single nucleotide polymorphisms snps may alter ligand binding balance pro anti inflammatory cytokines thereby modulating risk chronic inflammation cancer tlr4 polymorphisms may associated least nine types cancer intensively investigating tlr4 polymorphisms asp299gly rs4986790 thr399ile rs4986791 seems asp299gly thr399ile related increased risk precancerous gastric lesions possibly gastric cancer thr399ile also may connected gallbladder cancer polymorphisms apparently impact risk prostate cancer however data many snps associations different types cancer conflicting large well designed comprehensive studies various populations necessary solution problem short list tlr4 snps investigation may include tlr4_896a g asp299gly rs4986790 tlr4_1196c thr399ile rs4986791 thr135ala tlr4_1859 g rs11536858 tlr4_2032t c rs10116253 tlr4_2437a g rs1927914 tlr4_2856t c rs10759932 tlr4_3725 g c rs11536889 tlr4_7764 g rs1927911 tlr4_11350g c tlr4_11912 g rs2149356 tlr4_16649g c rs7873784 tlr4_17050t c rs11536891 pubmed","probabilities":0.9799733,"Title":"Impact of Toll-like receptor 4 polymorphisms on risk of cancer","Abstract":"Toll-like receptor 4 (TLR4) is one of the key immune system effectors playing the main role in recognition of viruses and bacteria. Dysregulation of the TLR4 signaling owing to single nucleotide polymorphisms (SNPs) may alter the ligand binding and balance between pro- and anti-inflammatory cytokines, thereby modulating the risk of chronic inflammation and cancer. TLR4 polymorphisms may be associated with at least nine types of cancer. The most intensively investigating TLR4 polymorphisms are Asp299Gly (rs4986790) and Thr399Ile (rs4986791). It seems to be that Asp299Gly and Thr399Ile are related to increased risk of precancerous gastric lesions, and, possibly, gastric cancer. Thr399Ile also may be connected with gallbladder cancer, and both of these polymorphisms apparently have no impact on risk of prostate cancer. However, the data about many SNPs and their associations with different types of cancer are conflicting, and further large, well-designed, comprehensive studies in various populations are necessary for solution of this problem. The short list of TLR4 SNPs for further investigation may include TLR4_896A/G (Asp299Gly, rs4986790), TLR4_1196C/T (Thr399Ile, rs4986791), Thr135Ala, TLR4_1859 G/A (rs11536858), TLR4_2032T/C (rs10116253), TLR4_2437A/G (rs1927914), TLR4_2856T/C (rs10759932), TLR4_3725 G/C (rs11536889), TLR4_7764 G/A (rs1927911), TLR4_11350G/C, TLR4_11912 G/T (rs2149356), TLR4_16649G/C (rs7873784), and TLR4_17050T/C (rs11536891).","Source":"PubMed","category":"HUMAN","training_data":"Impact of Toll-like receptor 4 polymorphisms on risk of cancer Toll-like receptor 4 (TLR4) is one of the key immune system effectors playing the main role in recognition of viruses and bacteria. Dysregulation of the TLR4 signaling owing to single nucleotide polymorphisms (SNPs) may alter the ligand binding and balance between pro- and anti-inflammatory cytokines, thereby modulating the risk of chronic inflammation and cancer. TLR4 polymorphisms may be associated with at least nine types of cancer. The most intensively investigating TLR4 polymorphisms are Asp299Gly (rs4986790) and Thr399Ile (rs4986791). It seems to be that Asp299Gly and Thr399Ile are related to increased risk of precancerous gastric lesions, and, possibly, gastric cancer. Thr399Ile also may be connected with gallbladder cancer, and both of these polymorphisms apparently have no impact on risk of prostate cancer. However, the data about many SNPs and their associations with different types of cancer are conflicting, and further large, well-designed, comprehensive studies in various populations are necessary for solution of this problem. The short list of TLR4 SNPs for further investigation may include TLR4_896A/G (Asp299Gly, rs4986790), TLR4_1196C/T (Thr399Ile, rs4986791), Thr135Ala, TLR4_1859 G/A (rs11536858), TLR4_2032T/C (rs10116253), TLR4_2437A/G (rs1927914), TLR4_2856T/C (rs10759932), TLR4_3725 G/C (rs11536889), TLR4_7764 G/A (rs1927911), TLR4_11350G/C, TLR4_11912 G/T (rs2149356), TLR4_16649G/C (rs7873784), and TLR4_17050T/C (rs11536891). PubMed","prediction_labels":"HUMAN"},{"cleaned":"screening malignancy primary sclerosing cholangitis psc primary sclerosing cholangitis psc frequently progressive fatal disease death cancer occurs significant subset patients psc patients psc 10 15 lifetime risk developing cholangiocarcinoma cca one third ccas present first year diagnosis psc remainder present frequency 1 5 year patients concomitant psc inflammatory bowel disease ibd 4 fold higher risk colorectal cancer crc patients ibd alone 10 fold higher risk crc general population risk diminish liver transplantation patient population also high frequency carcinoma gallbladder mass lesions risk hepatocellular carcinoma hcc presence cirrhosis uncertain two large cohort studies suggest hcc common causes cirrhosis although aasld guidelines recommend routine screening liver tumors patients psc recommend mri mrcp serum ca 19 9 levels patients psc every 6 months screen cca hcc pancreatic cancer gallbladder cancer screening colonoscopy diagnosis psc surveillance colonoscopies every 1 2 years performed psc ibd pubmed","probabilities":0.9799733,"Title":"Screening for malignancy in primary sclerosing cholangitis (PSC)","Abstract":"Primary sclerosing cholangitis (PSC) is a frequently progressive and fatal disease. Death from cancer occurs in a significant subset of patients with PSC. Patients with PSC have a 10 to 15 % lifetime risk of developing cholangiocarcinoma (CCA). About one third of CCAs are present in the first year after a diagnosis of PSC; the remainder are present with a frequency of about 1.5 % each year. Patients with concomitant PSC and inflammatory bowel disease (IBD) have a 4-fold higher risk of colorectal cancer (CRC) than patients with IBD alone and a 10-fold higher risk of CRC than the general population. The risk does not diminish with liver transplantation. This patient population also has a high frequency of carcinoma in gallbladder mass lesions. The risk for hepatocellular carcinoma (HCC) in the presence of cirrhosis is uncertain-two large cohort studies suggest that HCC is not as common as in other causes of cirrhosis. Although AASLD guidelines do not recommend routine screening for liver tumors in patients with PSC, we recommend MRI/MRCP and serum CA 19-9 levels in patients with PSC every 6 months to screen for CCA, HCC, pancreatic cancer, and gallbladder cancer. Screening colonoscopy at the diagnosis of PSC and surveillance colonoscopies every 1-2 years should be performed in those with PSC and IBD.","Source":"PubMed","category":"HUMAN","training_data":"Screening for malignancy in primary sclerosing cholangitis (PSC) Primary sclerosing cholangitis (PSC) is a frequently progressive and fatal disease. Death from cancer occurs in a significant subset of patients with PSC. Patients with PSC have a 10 to 15 % lifetime risk of developing cholangiocarcinoma (CCA). About one third of CCAs are present in the first year after a diagnosis of PSC; the remainder are present with a frequency of about 1.5 % each year. Patients with concomitant PSC and inflammatory bowel disease (IBD) have a 4-fold higher risk of colorectal cancer (CRC) than patients with IBD alone and a 10-fold higher risk of CRC than the general population. The risk does not diminish with liver transplantation. This patient population also has a high frequency of carcinoma in gallbladder mass lesions. The risk for hepatocellular carcinoma (HCC) in the presence of cirrhosis is uncertain-two large cohort studies suggest that HCC is not as common as in other causes of cirrhosis. Although AASLD guidelines do not recommend routine screening for liver tumors in patients with PSC, we recommend MRI/MRCP and serum CA 19-9 levels in patients with PSC every 6 months to screen for CCA, HCC, pancreatic cancer, and gallbladder cancer. Screening colonoscopy at the diagnosis of PSC and surveillance colonoscopies every 1-2 years should be performed in those with PSC and IBD. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance muc4 expression gallbladder carcinoma background mucins high molecular glycoproteins play protective lubricating roles various epithelial tissues deregulated expression mucins involved carcinogenesis tumor invasion muc4 expression identified poor prognostic factor pancreatobiliary carcinomas date relation muc4 expression prognosis gallbladder carcinoma remains determined authors examined muc4 expression gallbladder carcinoma investigated impact prognosis methods expression profiles muc4 muc1 muc2 mucins gallbladder carcinoma tissues 63 patients investigated using immunohistochemical staining results gallbladder carcinoma positive staining muc4 muc1 muc2 55 6 81 0 28 6 respectively significant correlation expression muc4 expression muc1 muc2 p 0 004 p 0 009 respectively univariate analysis showed muc4 expression p 0 047 differentiation p 0 05 stage p 0 05 lymph node metastasis p 0 001 significantly associated poor survival expression muc1 muc2 correlated survival backward stepwise multivariate analysis showed muc4 expression p 0 039 lymph node metastasis p 0 001 significant independent risk factors combined assessment muc4 muc2 expression muc4 positive muc2 negative group showed significantly worse outcome muc4 negative groups muc4 muc2 muc4 muc2 muc4 muc2 co expression group muc4 muc2 p 0 05 conclusions muc4 expression gallbladder carcinoma independent poor prognostic factor therefore muc4 expression may useful marker predict outcome patients surgically resected gallbladder carcinoma muc2 expression may prognostic value combined muc4 expression google scholar","probabilities":0.7777778,"Title":"Prognostic Significance Of Muc4 Expression In Gallbladder Carcinoma","Abstract":"Background\nMucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis.\nMethods\nThe expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining.\nResults\nFor gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05).\nConclusions\nMUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression.","Source":"Google Scholar","category":"ANIMAL","training_data":"Prognostic Significance Of Muc4 Expression In Gallbladder Carcinoma Background\nMucins are high molecular glycoproteins and play protective and lubricating roles in various epithelial tissues. Deregulated expression of mucins is involved in carcinogenesis and tumor invasion. MUC4 expression has been identified as a poor prognostic factor in pancreatobiliary carcinomas. To date, the relation between MUC4 expression and prognosis in gallbladder carcinoma remains to be determined. Authors examined MUC4 expression in gallbladder carcinoma and investigated its impact on prognosis.\nMethods\nThe expression profiles of MUC4, MUC1, MUC2 mucins in gallbladder carcinoma tissues from 63 patients were investigated using immunohistochemical staining.\nResults\nFor gallbladder carcinoma, positive staining of MUC4, MUC1, and MUC2 was 55.6%, 81.0%, 28.6%, respectively. There was a significant correlation between the expression of MUC4 and the expression of MUC1 or MUC2 (p = 0.004, p = 0.009, respectively). Univariate analysis showed that MUC4 expression (p = 0.047), differentiation (p < 0.05), T-stage (p < 0.05) and lymph node metastasis (p < 0.001) were significantly associated with poor survival. Expression of MUC1 and MUC2 was not correlated to survival. The backward stepwise multivariate analysis showed that MUC4 expression (p = 0.039) and lymph node metastasis (p = 0.001) were significant independent risk factors. In combined assessment of MUC4 and MUC2 expression, MUC4 positive and MUC2 negative group showed a significantly worse outcome than MUC4 negative groups(MUC4-/MUC2+ and MUC4-/MUC2-) and MUC4/MUC2 co-expression group(MUC4+/MUC2+) (p < 0.05).\nConclusions\nMUC4 expression in gallbladder carcinoma is an independent poor prognostic factor. Therefore, MUC4 expression may be a useful marker to predict the outcome of patients with surgically resected gallbladder carcinoma. MUC2 expression may have prognostic value when combined with MUC4 expression. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"long term outcome surgical resection cholangiocarcinoma prognostic index value objective investigate prognostic factors patients cholangiocarcinoma establish prognostic model evaluate prognosis methods 169 cases cholangiocarcinoma analyzed retrospectively clinicopathological factors evaluated using univariate multivariate analysis prognostic index pi calculated based results multivariate analysis patients different pi divided 3 groups order compare survival rate group draw survival curves individual expected survival rate calculated based prognostic cox model pi pi equation built included significant variables coefficients follow formula pi 1 lymph node metastasis 2 cea level 3 surgical margin results univariate analysis showed cea lymph node metastasis surgical margin ajcc staging tumor differentiation adjuvant chemotherapy prognostic impacts difference statistically significant p 0 05 cox multivariate analysis showed cea lymph node metastasis surgical margin three separate prognostic factors according different pi patients divided high risk group middle risk group low risk group three groups statistically significant difference survival rate p 0 05 conclusion racical resection key improve long term survival rate cholangiocarcinoma using prognostic cox model pi prognosis patients estimated individualized clinical treatment conducted pubmed","probabilities":0.9799733,"Title":"Long-term outcome after surgical resection for cholangiocarcinoma and prognostic index value","Abstract":"OBJECTIVE: To investigate the prognostic factors of patients with cholangiocarcinoma and establish a prognostic model to evaluate the prognosis. METHODS: 169 cases of cholangiocarcinoma were analyzed retrospectively. Clinicopathological factors were evaluated using univariate and multivariate analysis. Prognostic index (PI) was calculated based on the results of multivariate analysis. Patients with different PI were divided into 3 groups in order to compare the survival rate of each group and draw the survival curves. Individual expected survival rate was calculated based on the prognostic Cox model and PI. The PI equation was built that included all significant variables and coefficients as follow formula: PI = (β1 × lymph node metastasis) + (β2 × CEA level) - (β3 × surgical margin). RESULTS: Univariate analysis showed that CEA, lymph node metastasis, surgical margin, AJCC staging, tumor differentiation and adjuvant chemotherapy were prognostic impacts. The difference was statistically significant (p < 0.05). Cox multivariate analysis showed that CEA, lymph node metastasis and surgical margin are three separate prognostic factors. According to different PI, patients were divided into high-risk group, middle-risk group and low-risk group and three groups were statistically significant difference in survival rate (P < 0.05). CONCLUSION: Racical resection is the key to improve the long-term survival rate of cholangiocarcinoma. By using prognostic Cox model and the PI, the prognosis of patients could be estimated and individualized clinical treatment could be conducted.","Source":"PubMed","category":"HUMAN","training_data":"Long-term outcome after surgical resection for cholangiocarcinoma and prognostic index value OBJECTIVE: To investigate the prognostic factors of patients with cholangiocarcinoma and establish a prognostic model to evaluate the prognosis. METHODS: 169 cases of cholangiocarcinoma were analyzed retrospectively. Clinicopathological factors were evaluated using univariate and multivariate analysis. Prognostic index (PI) was calculated based on the results of multivariate analysis. Patients with different PI were divided into 3 groups in order to compare the survival rate of each group and draw the survival curves. Individual expected survival rate was calculated based on the prognostic Cox model and PI. The PI equation was built that included all significant variables and coefficients as follow formula: PI = (β1 × lymph node metastasis) + (β2 × CEA level) - (β3 × surgical margin). RESULTS: Univariate analysis showed that CEA, lymph node metastasis, surgical margin, AJCC staging, tumor differentiation and adjuvant chemotherapy were prognostic impacts. The difference was statistically significant (p < 0.05). Cox multivariate analysis showed that CEA, lymph node metastasis and surgical margin are three separate prognostic factors. According to different PI, patients were divided into high-risk group, middle-risk group and low-risk group and three groups were statistically significant difference in survival rate (P < 0.05). CONCLUSION: Racical resection is the key to improve the long-term survival rate of cholangiocarcinoma. By using prognostic Cox model and the PI, the prognosis of patients could be estimated and individualized clinical treatment could be conducted. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical presentation prognostic factors intrahepatic extrahepatic cholangiocarcinoma tertiary care centre background incidence cholangiocarcinoma rising accurate predictors survival diagnosis well defined aim clarify clinical presentation prognostic factors intrahepatic cholangiocarcinoma extrahepatic cholangiocarcinoma contemporary cohort patients methods records consecutive patients university michigan hospital diagnosed cholangiocarcinoma january 2003 april 2008 reviewed results 136 patients cholangiocarcinoma 79 intra 57 extrahepatic cholangiocarcinoma median survival 27 3 months 25 8 months intrahepatic cholangiocarcinoma 30 3 months extrahepatic cholangiocarcinoma independent predictors mortality presentation multivariate analysis elevated bilirubin level hr 1 04 95 ci 1 01 1 07 ca 19 9 levels 100 u ml hr 1 90 95 ci 1 17 3 08 stage disease hr 1 51 95 ci 1 16 1 96 adjusting baseline prognostic factors surgical therapy associated improved survival hr 0 48 95 ci 0 26 0 88 significant differences regarding clinical presentation disease stage p 0 98 survival p 0 51 intra extrahepatic cholangiocarcinoma conclusions survival cholangiocarcinoma remains poor significant difference outcomes intra extrahepatic cholangiocarcinoma stage disease bilirubin level ca 19 9 level important prognostic factors presentation surgical therapy provides similar efficacy tumours adjusted prognostic variables stn","probabilities":0.9799733,"Title":"The Clinical Presentation And Prognostic Factors For Intrahepatic And Extrahepatic Cholangiocarcinoma In A Tertiary Care Centre","Abstract":"Background: The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined. \n\n Aim: To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients. \n\n Methods: Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed. \n\n Results: In all, 136 patients had cholangiocarcinoma (79 intra- and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months-25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01-1.07), CA 19-9 levels >100 U/mL (HR 1.90, 95%CI 1.17-3.08) and stage of disease (HR 1.51, 95%CI 1.16-1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26-0.88). There were no significant differences regarding clinical presentation, disease stage (P = 0.98), and survival (P = 0.51) between intra- and extrahepatic cholangiocarcinoma. \n\n Conclusions: Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra- and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19-9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables.","Source":"STN","category":"HUMAN","training_data":"The Clinical Presentation And Prognostic Factors For Intrahepatic And Extrahepatic Cholangiocarcinoma In A Tertiary Care Centre Background: The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined. \n\n Aim: To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients. \n\n Methods: Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed. \n\n Results: In all, 136 patients had cholangiocarcinoma (79 intra- and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months-25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01-1.07), CA 19-9 levels >100 U/mL (HR 1.90, 95%CI 1.17-3.08) and stage of disease (HR 1.51, 95%CI 1.16-1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26-0.88). There were no significant differences regarding clinical presentation, disease stage (P = 0.98), and survival (P = 0.51) between intra- and extrahepatic cholangiocarcinoma. \n\n Conclusions: Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra- and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19-9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables. STN","prediction_labels":"HUMAN"},{"cleaned":"incidence patterns survival gallbladder cancer four decades impact age ethnicity socioeconomic status treatment modalities background gallbladder cancer gbc rare tumor often presents advanced stage associated poor prognosis little known incidence patterns factors influence outcomes gbc methods gbc cases diagnosed 1973 2012 identified using surveillance epidemiology end results seer database annual percent change apc incidence rates calculated time period retrospective cohort 16547 gbc patients diagnosed 1973 2008 analyzed using chi square test cox proportional hazards model results overall incidence gbc decreased last four decades significant increase observed among blacks table subsets population belonging hispanic origin ethnicities including american indians significant decrease gbc incidence 5 year overall survival os disease specific survival dss 12 8 11 7 respectively poor prognostic factors included age 50 years hr 1 115 male gender hr 1 082 multi level variables poor prognosis included lack high school education higher grade stage diagnosis p 0 0001 hand marital status hispanic ethnicity higher income level treatment associated better os dss p 0 005 conclusions analysis suggests overall decrease incidence gbc significant decrease among hispanics american indians possibly due increasing early cholecystectomy rates however incidence rates gbc seem increasing among blacks furthermore younger age diagnosis associated poor outcomes additional studies required validate findings understand molecular basis heterogeneity outcomes google scholar","probabilities":0.9799733,"Title":"Incidence Patterns And Survival Of Gallbladder Cancer Over Four Decades: Impact Of Age Ethnicity Socioeconomic Status And Treatment Modalities","Abstract":"Background: Gallbladder cancer (GBC) is a rare tumor that often presents at an advanced stage and is associated with a poor prognosis. Little is known about the incidence patterns and factors that influence outcomes in GBC. Methods: GBC cases diagnosed between 1973 and 2012 were identified using Surveillance, Epidemiology and End Results (SEER) database and annual percent change (APC) in the incidence rates were calculated for the same time period. A retrospective cohort of 16547 GBC patients diagnosed from 1973 to 2008 was further analyzed using Chi-square test and Cox proportional hazards model. Results: While the overall incidence of GBC decreased over last four decades, a significant increase was observed among Blacks (Table). Subsets of population belonging to Hispanic origin and other ethnicities (including American Indians) had a significant decrease in GBC incidence. 5-year overall survival (OS) and disease specific survival (DSS) were 12.8% and 11.7%, respectively. Poor prognostic factors included age < 50 years (HR 1.115) and male gender (HR 1.082). Other multi-level variables with poor prognosis included lack of high school education, and higher grade and stage at diagnosis (p<0.0001). On the other hand, marital status, Hispanic ethnicity, higher income level and treatment were associated with better OS and DSS (p<0.005). Conclusions: Our analysis suggests an overall decrease in incidence of GBC with a significant decrease among Hispanics and American Indians, possibly due to increasing early cholecystectomy rates. However, the incidence rates of GBC seem to be increasing among Blacks. Furthermore, younger age at diagnosis was associated with poor outcomes. Additional studies are required to validate these findings and understand the molecular basis for this heterogeneity in outcomes.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidence Patterns And Survival Of Gallbladder Cancer Over Four Decades: Impact Of Age Ethnicity Socioeconomic Status And Treatment Modalities Background: Gallbladder cancer (GBC) is a rare tumor that often presents at an advanced stage and is associated with a poor prognosis. Little is known about the incidence patterns and factors that influence outcomes in GBC. Methods: GBC cases diagnosed between 1973 and 2012 were identified using Surveillance, Epidemiology and End Results (SEER) database and annual percent change (APC) in the incidence rates were calculated for the same time period. A retrospective cohort of 16547 GBC patients diagnosed from 1973 to 2008 was further analyzed using Chi-square test and Cox proportional hazards model. Results: While the overall incidence of GBC decreased over last four decades, a significant increase was observed among Blacks (Table). Subsets of population belonging to Hispanic origin and other ethnicities (including American Indians) had a significant decrease in GBC incidence. 5-year overall survival (OS) and disease specific survival (DSS) were 12.8% and 11.7%, respectively. Poor prognostic factors included age < 50 years (HR 1.115) and male gender (HR 1.082). Other multi-level variables with poor prognosis included lack of high school education, and higher grade and stage at diagnosis (p<0.0001). On the other hand, marital status, Hispanic ethnicity, higher income level and treatment were associated with better OS and DSS (p<0.005). Conclusions: Our analysis suggests an overall decrease in incidence of GBC with a significant decrease among Hispanics and American Indians, possibly due to increasing early cholecystectomy rates. However, the incidence rates of GBC seem to be increasing among Blacks. Furthermore, younger age at diagnosis was associated with poor outcomes. Additional studies are required to validate these findings and understand the molecular basis for this heterogeneity in outcomes. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"extent liver resection hilar cholangiocarcinoma klatskin tumor much enough background hilar resection combination extended liver resections resulted higher rate r0 resections increased survival patients hilar cholangiocarcinoma hcca aggressive surgical approach however associated high rates operative morbidity mortality largely due postresectional liver failure previously reported series resection hcca r0 resection rate 59 mortality rate 10 study assessed mortality extended liver resections optimizing liver functional reserve application parenchyma sparing techniques methods 2008 june 2010 41 consecutive patients underwent resection suspicion hcca preoperative workup included staging laparoscopy preoperative biliary drainage assessment volume function future remnant liver radiation therapy prevent seeding metastases modified right left extended hemihepatectomies performed preserving parts segments 4 8 respectively pursuing complete excision tumor outcomes resection evaluated results majority resections 78 performed bismuth type iii iv tumors preoperative biliary drainage undertaken 37 90 patients hilar resection combination liver resection performed 35 85 patients resections 61 modified extended resections including central liver resections r0 resection rate 92 postoperative morbidity mortality rates 54 7 respectively conclusion strategies optimize liver function reduce removal functional liver parenchyma associated decrease mortality 7 undertaking extended resection hcca r0 resection rate 92 stn","probabilities":0.9799733,"Title":"Extent Of Liver Resection For Hilar Cholangiocarcinoma (Klatskin Tumor): How Much Is Enough?","Abstract":"Background: Hilar resection in combination with extended liver resections has resulted in a higher rate of R0 resections and increased survival in patients with hilar cholangiocarcinoma (HCCA). This aggressive surgical approach is, however, associated with high rates of operative morbidity and mortality, largely due to postresectional liver failure. We previously reported a series after resection of HCCA in which R0 resection rate was 59% with a mortality rate of 10%. In this study, we assessed mortality of extended liver resections after optimizing liver functional reserve and application of parenchyma-sparing techniques. \r\n\r\n Methods: From 2008 until June 2010, 41 consecutive patients underwent resection on the suspicion of HCCA. Preoperative workup included staging laparoscopy, preoperative biliary drainage, assessment of volume/function of future remnant liver and radiation therapy to prevent seeding metastases. Modified right and left extended hemihepatectomies were performed preserving parts of segments 4 and 8, respectively, while pursuing complete excision of the tumor. Outcomes of resection were evaluated. \r\n\r\n Results: The majority of resections (78%) were performed for Bismuth type III-IV tumors. Preoperative biliary drainage was undertaken in 37 (90%) patients. Hilar resection in combination with liver resection was performed in 35 (85%) patients. Of these resections, 61% were modified extended resections including central liver resections. The R0 resection rate was 92%. Postoperative morbidity and mortality rates were 54 and 7%, respectively. \r\n\r\n Conclusion: Strategies to optimize liver function and to reduce removal of functional liver parenchyma were associated with a decrease in mortality (7%) while undertaking extended resection for HCCA with an R0 resection rate of 92%.","Source":"STN","category":"HUMAN","training_data":"Extent Of Liver Resection For Hilar Cholangiocarcinoma (Klatskin Tumor): How Much Is Enough? Background: Hilar resection in combination with extended liver resections has resulted in a higher rate of R0 resections and increased survival in patients with hilar cholangiocarcinoma (HCCA). This aggressive surgical approach is, however, associated with high rates of operative morbidity and mortality, largely due to postresectional liver failure. We previously reported a series after resection of HCCA in which R0 resection rate was 59% with a mortality rate of 10%. In this study, we assessed mortality of extended liver resections after optimizing liver functional reserve and application of parenchyma-sparing techniques. \r\n\r\n Methods: From 2008 until June 2010, 41 consecutive patients underwent resection on the suspicion of HCCA. Preoperative workup included staging laparoscopy, preoperative biliary drainage, assessment of volume/function of future remnant liver and radiation therapy to prevent seeding metastases. Modified right and left extended hemihepatectomies were performed preserving parts of segments 4 and 8, respectively, while pursuing complete excision of the tumor. Outcomes of resection were evaluated. \r\n\r\n Results: The majority of resections (78%) were performed for Bismuth type III-IV tumors. Preoperative biliary drainage was undertaken in 37 (90%) patients. Hilar resection in combination with liver resection was performed in 35 (85%) patients. Of these resections, 61% were modified extended resections including central liver resections. The R0 resection rate was 92%. Postoperative morbidity and mortality rates were 54 and 7%, respectively. \r\n\r\n Conclusion: Strategies to optimize liver function and to reduce removal of functional liver parenchyma were associated with a decrease in mortality (7%) while undertaking extended resection for HCCA with an R0 resection rate of 92%. STN","prediction_labels":"HUMAN"},{"cleaned":"study correlation neutrophil tolymphocyte ratio prognostic factor cholangiocarcinoma objective aimed verify nlr used another prognostic factor cholangiocarcinoma methods recruited 171 patients cholangiocarcinoma proven pathological imaging confirmation january 2006 december 2015 baseline characteristics laboratory data modalities treatment therapeutic outcomes collected associations clinical characteristics nlr laboratory variables including tumor markers well survival investigated regression analysis proper cut level nlr also identified using sensitivity analysis comparison patients nlr 2 nlr 2 performed using logistic regression analysis results 171 patients categorized 3 groups according treatment modalities included palliative chemotherapy n 77 45 adjuvant therapy n 37 21 6 surgery group n 57 33 cut nlr value 2 selected predict prognosis 74 sensitivity 53 specificity patients nlr 2 across study timeline treatment best survival median os 34 8 37 1 months patients initial nlr 2 median overall survival os progression free survival pfs disease free survival dfs 34 8 50 6 months respectively compared median os 21 6 months p 0 001 median pfs dfs 16 6 months p 0 004 nlr 2 multivariate analysis demonstrated high level cea ca19 9 significant predictors poor pfs dfs hr 2 29 2 03 p 0 016 0 04 respectively worse os predicted nlr 2 hr 1 76 p 0 021 ca 19 1 300 hr 1 79 p 0 009 ecog 2 hr 6 24 p 0 016 conclusion nlr considered another independent prognostic factor predict survival patients cholangiocarcinoma since nlr cheap simple available test propose use useful biomarker predict prognosis cholangiocarcinoma google scholar","probabilities":0.9799733,"Title":"A Study Of Correlation Between Neutrophil-Tolymphocyte Ratio As A Prognostic Factor In Cholangiocarcinoma","Abstract":"Objective: We aimed to verify if NLR could be used as another prognostic factor in cholangiocarcinoma. \n Methods: We recruited 171 patients with cholangiocarcinoma, proven by pathological and/or imaging confirmation from January 2006 to December 2015. Baseline characteristics, laboratory data, modalities of treatment, and therapeutic outcomes were collected. Associations between clinical characteristics, NLR, laboratory variables including tumor markers, as well as survival were investigated by regression analysis. The proper cut-off level of NLR was also identified using sensitivity analysis. Comparison between patients with NLR<2 and NLR ≥2 was performed using logistic regression analysis. Results: 171 patients were categorized into 3 groups according to treatment modalities, which included palliative chemotherapy (N=77, 45%), adjuvant therapy (N=37, 21.6%), and surgery group (N=57, 33%). The cut-off NLR value of 2 was selected to predict prognosis with 74% sensitivity and 53% specificity. Patients with NLR < 2 across the study timeline (before, during, and after treatment) had the best survival (Median OS=34.8 and 37.1 months). Patients with initial NLR < 2, had median overall survival (OS) and progression-free survival (PFS)/disease-free survival (DFS) of 34.8 and 50.6 months, respectively compared to median OS of 21.6 months (P = 0.001) and median PFS/DFS of 16.6 months (P = 0.004) in those with NLR ≥ 2. Multivariate analysis demonstrated that high level of CEA and CA19-9 were significant predictors of poor PFS/DFS with HR=2.29 and 2.03, P=0.016 and 0.04, respectively). Worse OS was predicted by NLR ≥ 2 (HR 1.76, P=0.021), CA 19-1 > 300 (HR 1.79, P=0.009), and ECOG ≥ 2 (HR 6.24, P=0.016). Conclusion: NLR can be considered as another independent prognostic factor to predict survival in patients with cholangiocarcinoma. Since NLR is a cheap, simple, and available test, we propose to use it as a useful biomarker to predict prognosis of cholangiocarcinoma.","Source":"Google Scholar","category":"HUMAN","training_data":"A Study Of Correlation Between Neutrophil-Tolymphocyte Ratio As A Prognostic Factor In Cholangiocarcinoma Objective: We aimed to verify if NLR could be used as another prognostic factor in cholangiocarcinoma. \n Methods: We recruited 171 patients with cholangiocarcinoma, proven by pathological and/or imaging confirmation from January 2006 to December 2015. Baseline characteristics, laboratory data, modalities of treatment, and therapeutic outcomes were collected. Associations between clinical characteristics, NLR, laboratory variables including tumor markers, as well as survival were investigated by regression analysis. The proper cut-off level of NLR was also identified using sensitivity analysis. Comparison between patients with NLR<2 and NLR ≥2 was performed using logistic regression analysis. Results: 171 patients were categorized into 3 groups according to treatment modalities, which included palliative chemotherapy (N=77, 45%), adjuvant therapy (N=37, 21.6%), and surgery group (N=57, 33%). The cut-off NLR value of 2 was selected to predict prognosis with 74% sensitivity and 53% specificity. Patients with NLR < 2 across the study timeline (before, during, and after treatment) had the best survival (Median OS=34.8 and 37.1 months). Patients with initial NLR < 2, had median overall survival (OS) and progression-free survival (PFS)/disease-free survival (DFS) of 34.8 and 50.6 months, respectively compared to median OS of 21.6 months (P = 0.001) and median PFS/DFS of 16.6 months (P = 0.004) in those with NLR ≥ 2. Multivariate analysis demonstrated that high level of CEA and CA19-9 were significant predictors of poor PFS/DFS with HR=2.29 and 2.03, P=0.016 and 0.04, respectively). Worse OS was predicted by NLR ≥ 2 (HR 1.76, P=0.021), CA 19-1 > 300 (HR 1.79, P=0.009), and ECOG ≥ 2 (HR 6.24, P=0.016). Conclusion: NLR can be considered as another independent prognostic factor to predict survival in patients with cholangiocarcinoma. Since NLR is a cheap, simple, and available test, we propose to use it as a useful biomarker to predict prognosis of cholangiocarcinoma. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinicopathologic correlations gallbladder cancer ethnicity new mexico 1980 2009 background gallbladder cancer gbca rare malignancy however within u incidence varies geographically gbca higher occurrence american indian ai population versus non hispanic whites nhw hispanics h goal study determine clinicopathologic features correlate ethnicity methods incident gbca diagnosed new mexico 1980 2009 identified population based new mexico tumor registry average age adjusted incidence rates calculated direct method using united states 2000 standard population chi squared statistic used assess ethnicity differences case distribution diagnosis sex age stage grade cause specific survival calculated kaplan meier method assessed log rank statistic results gbca incidence rates new mexico highest ai 7 6 per 100 000 95 confidence interval ci 6 5 8 9 followed h 2 8 per 100 000 95 ci 2 5 3 2 nhw 1 0 per 100 000 95 ci 0 9 1 1 females predominantly affected table median ages varied among nhw 74 years h 71 years ai 69 years appreciable differences respect stage tumor grade cause specific survival 60 months also similar among nhw 20 25 h 17 94 ai 22 43 log rank p value 0 7388 conclusions gbca higher prevalence ai regardless shares similar characteristics evaluated ethnicities predominantly disease older females similar tumor grade stage equally poor survival google scholar","probabilities":0.9799733,"Title":"Clinicopathologic Correlations Of Gallbladder Cancer By Ethnicity In New Mexico 1980-2009","Abstract":"Background: Gallbladder cancer (GBCA) is a rare malignancy; however, within the U.S. incidence varies geographically. GBCA has a higher occurrence in the American Indian (AI) population versus non-Hispanic whites (NHW) and Hispanics (H). The goal of the study is to determine if clinicopathologic features correlate with ethnicity. Methods: Incident GBCA diagnosed in New Mexico from 1980-2009 were identified from the population-based New Mexico Tumor Registry. Average age-adjusted incidence rates were calculated by direct method using the United States 2000 standard population. Chi-squared statistic was used to assess ethnicity differences in case distribution at diagnosis by sex, age, stage and grade. Cause-specific survival was calculated by the Kaplan-Meier method and assessed with log-rank statistic. Results: GBCA incidence rates in New Mexico are highest for AI (7.6 per 100,000–95% confidence interval (CI)=6.5-8.9), followed by H (2.8 per 100,000 – 95% CI=2.5-3.2) and NHW (1.0 per 100,000 – 95% CI=0.9-1.1). Females are predominantly affected (Table). Median ages varied among NHW (74 years), H (71 years) and AI (69 years). There are no appreciable differences with respect to stage and tumor grade. Cause-specific survival at 60 months is also similar among NHW (20.25%), H (17.94%), and AI (22.43%) (log-rank p-value=0.7388). Conclusions: GBCA has a higher prevalence in AI. Regardless it shares similar characteristics in all evaluated ethnicities as it is predominantly a disease of older females, with similar tumor grade and stage and with equally poor survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Clinicopathologic Correlations Of Gallbladder Cancer By Ethnicity In New Mexico 1980-2009 Background: Gallbladder cancer (GBCA) is a rare malignancy; however, within the U.S. incidence varies geographically. GBCA has a higher occurrence in the American Indian (AI) population versus non-Hispanic whites (NHW) and Hispanics (H). The goal of the study is to determine if clinicopathologic features correlate with ethnicity. Methods: Incident GBCA diagnosed in New Mexico from 1980-2009 were identified from the population-based New Mexico Tumor Registry. Average age-adjusted incidence rates were calculated by direct method using the United States 2000 standard population. Chi-squared statistic was used to assess ethnicity differences in case distribution at diagnosis by sex, age, stage and grade. Cause-specific survival was calculated by the Kaplan-Meier method and assessed with log-rank statistic. Results: GBCA incidence rates in New Mexico are highest for AI (7.6 per 100,000–95% confidence interval (CI)=6.5-8.9), followed by H (2.8 per 100,000 – 95% CI=2.5-3.2) and NHW (1.0 per 100,000 – 95% CI=0.9-1.1). Females are predominantly affected (Table). Median ages varied among NHW (74 years), H (71 years) and AI (69 years). There are no appreciable differences with respect to stage and tumor grade. Cause-specific survival at 60 months is also similar among NHW (20.25%), H (17.94%), and AI (22.43%) (log-rank p-value=0.7388). Conclusions: GBCA has a higher prevalence in AI. Regardless it shares similar characteristics in all evaluated ethnicities as it is predominantly a disease of older females, with similar tumor grade and stage and with equally poor survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"conversion surgery downsizing chemotherapy initially unresectable locally advanced biliary tract cancer backgound treated patients initially unresectable locally advanced biliary tract cancer btc administering gemcitabine found surgical resection became feasible downsized patients aim study investigate usefulness downsizing combination chemotherapy using gemcitabine plus cisplatin treat initially unresectable locally advanced btc methods subjects study 150 consecutive patients treated btc october 2011 april 2014 downsizing chemotherapy carried 39 patients 26 0 whose lesions unresectable locally advanced btc results reduction tumor size downsizing chemotherapy seen 18 patients surgical resection performed 10 39 patients 25 6 median survival time patients surgical resection following downsizing chemotherapy chemotherapy alone 17 9 12 4 months respectively p 0 0378 according historical comparison gemcitabine gemcitabine plus cisplatin chemotherapy significant difference overall survival however significant difference pathologic response rate grade iii higher patients gemcitabine plus cisplatin chemotherapy compared gemcitabine monotherapy conclusions preoperative downsizing chemotherapy gemcitabine plus cisplatin provides longer survival conversion surgical resection patients initially unresectable locally advanced btc may potential disease eradication new multidisciplinary approach initially unresectable locally advanced btc google scholar","probabilities":0.9799733,"Title":"Conversion Surgery After Downsizing Chemotherapy For Initially Unresectable Locally Advanced Biliary Tract Cancer","Abstract":"Backgound\nWe have treated patients with initially unresectable locally advanced biliary tract cancer (BTC) by administering gemcitabine and have found that surgical resection became feasible in some downsized patients. The aim of this study was to investigate the usefulness of downsizing combination chemotherapy using gemcitabine plus cisplatin to treat initially unresectable locally advanced BTC.\nMethods\nThe subjects of the study were 150 consecutive patients who were treated for BTC between October 2011 and April 2014. Downsizing chemotherapy was carried out for 39 patients (26.0 %) whose lesions were unresectable because of locally advanced BTC.\nResults\nReduction in tumor size with downsizing chemotherapy was seen in 18 patients, and surgical resection was performed in 10 of 39 patients (25.6 %). Median survival time in patients with surgical resection following downsizing chemotherapy and those with chemotherapy alone was 17.9 and 12.4 months, respectively (p = 0.0378). According to the historical comparison between gemcitabine and gemcitabine plus cisplatin chemotherapy, there is no significant difference in overall survival. However, there was a significant difference for the pathologic response rate (≥Grade III) to be higher in patients with gemcitabine plus cisplatin chemotherapy compared with gemcitabine monotherapy.\nConclusions\nPreoperative downsizing chemotherapy with gemcitabine plus cisplatin provides longer survival by the conversion to the surgical resection in patients with initially unresectable locally advanced BTC. It may have the potential for disease eradication as a new multidisciplinary approach for initially unresectable locally advanced BTC.","Source":"Google Scholar","category":"HUMAN","training_data":"Conversion Surgery After Downsizing Chemotherapy For Initially Unresectable Locally Advanced Biliary Tract Cancer Backgound\nWe have treated patients with initially unresectable locally advanced biliary tract cancer (BTC) by administering gemcitabine and have found that surgical resection became feasible in some downsized patients. The aim of this study was to investigate the usefulness of downsizing combination chemotherapy using gemcitabine plus cisplatin to treat initially unresectable locally advanced BTC.\nMethods\nThe subjects of the study were 150 consecutive patients who were treated for BTC between October 2011 and April 2014. Downsizing chemotherapy was carried out for 39 patients (26.0 %) whose lesions were unresectable because of locally advanced BTC.\nResults\nReduction in tumor size with downsizing chemotherapy was seen in 18 patients, and surgical resection was performed in 10 of 39 patients (25.6 %). Median survival time in patients with surgical resection following downsizing chemotherapy and those with chemotherapy alone was 17.9 and 12.4 months, respectively (p = 0.0378). According to the historical comparison between gemcitabine and gemcitabine plus cisplatin chemotherapy, there is no significant difference in overall survival. However, there was a significant difference for the pathologic response rate (≥Grade III) to be higher in patients with gemcitabine plus cisplatin chemotherapy compared with gemcitabine monotherapy.\nConclusions\nPreoperative downsizing chemotherapy with gemcitabine plus cisplatin provides longer survival by the conversion to the surgical resection in patients with initially unresectable locally advanced BTC. It may have the potential for disease eradication as a new multidisciplinary approach for initially unresectable locally advanced BTC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"surgical outcome hepatopancreatoduodenectomy associated hemihepatectomy extended liver resection biliary cancers introduction hepatopancreatoduodenectomy associated hemihepatectomy extended liver resection hpd occasionally indicated patients advanced gallbladder bile duct cancers still highly invasive surgical procedure feasibility invasive procedure biliary cancers fully invastigated aims methods aim study review surgical outcome hpd terms case series single surgeon three japanese tertiary referral centers consecutive one hundred one hepatobiliary resections caudate lobectomy carried single surgeon ts national cancer center tokyo aichi cancer center nagoya aichi medical university nagakute since 2002 2016 14 included 13 patients bile duct cancer one gallbladder cancer underwent hpd analyzed essentially liver transection performed terms pean clamp crushing method intermittent inflow occlusion pancreatojujunostomy carried terms duct mucosa anastomosis results 9 men 5 women median age 66 years old 34 81 patients underwent preoperative biliary drainage 12 patients underwent preoperative portal vein embolization extent liver resection left hemihepatectomy performed 2 right hemihepatectomy 11 right trisectionectomy 1 patient respectively combined portal vein resection reconstruction carried 6 42 9 hepatic arterial resection reconstruction one patients 7 1 median operation time 822 minutes 518 992 median intraoperative blood loss 1716 ml 730 2930 respectively although one patient underwent left trisectionectomy segmental portal vein resection reconstruction 101 hepatobiliary resections resulted postoperative mortality mortality rate 1 0 hpd accomplished zero mortality studied period histologically proximal bile duct margins confirmed positive cancer cells two patients bile duct cancer r1 resection four patients bile duct cancer survived 5 years without evidence tumor recurrence hand one patient gallbladder cancer died recurrence 7 months surgery conclusion hpd may become safe potentially feasible surgical procedure bile duct cancer indication hpd gallbladder cancer elucidated investigations terms large case series google scholar","probabilities":0.9799733,"Title":"Surgical Outcome Of Hepatopancreatoduodenectomy Associated With Hemihepatectomy Or More Extended Liver Resection For Biliary Cancers","Abstract":"Introduction: Hepatopancreatoduodenectomy associated with hemihepatectomy\nor more extended liver resection (HPD) is occasionally indicated in patients with\nadvanced gallbladder or bile duct cancers, and is still a highly invasive surgical\nprocedure. Feasibility of this invasive procedure for biliary cancers has not fully\ninvastigated.\nAims & Methods: The aim of this study is to review surgical outcome of HPD in\nterms of case series of a single surgeon at three Japanese tertiary referral centers.\nConsecutive one hundred one hepatobiliary resections with caudate lobectomy\nwere carried out by a single surgeon (TS) at National Cancer Center, Tokyo,\nAichi Cancer Center, Nagoya, and Aichi Medical University, Nagakute since\n2002 and 2016. Of these 14 included 13 patients with bile duct cancer and one\nwith gallbladder cancer underwent HPD were analyzed. Essentially, liver transection\nwas performed in terms of Pean clamp crushing method under intermittent\ninflow occlusion and pancreatojujunostomy was carried out in terms of duct to\nmucosa anastomosis.\nResults: There were 9 men and 5 women. The median age was 66 years old (34–\n81). All patients underwent preoperative biliary drainage and 12 patients underwent\npreoperative portal vein embolization. As to the extent of liver resection,\nleft hemihepatectomy was performed in 2, right hemihepatectomy in 11, and\nright trisectionectomy in 1 patient, respectively. Combined portal vein resection\nand reconstruction was carried out in 6 (42.9%), and hepatic arterial resection\nand reconstruction in one patients (7.1%). The median operation time was 822\nminutes (518–992), and the median intraoperative blood loss was 1716 ml (730–\n2930), respectively. Although one patient underwent left trisectionectomy with\nsegmental portal vein resection and reconstruction of 101 hepatobiliary resections\nresulted in the postoperative mortality (mortality rate 1.0%), HPD was\naccomplished with zero mortality in this studied period. Histologically, the proximal\nbile duct margins were confirmed positive for cancer cells in two patients\nwith bile duct cancer (R1 resection). Four patients with bile duct cancer survived\nmore than 5 years without evidence of tumor recurrence, on the other hand one\npatient with gallbladder cancer died from recurrence 7 months after the surgery.\nConclusion: HPD may become a safe and potentially feasible surgical procedure\nfor bile duct cancer, the indication of HPD for gallbladder cancer should be\nelucidated for further investigations in terms of large case series.","Source":"Google Scholar","category":"HUMAN","training_data":"Surgical Outcome Of Hepatopancreatoduodenectomy Associated With Hemihepatectomy Or More Extended Liver Resection For Biliary Cancers Introduction: Hepatopancreatoduodenectomy associated with hemihepatectomy\nor more extended liver resection (HPD) is occasionally indicated in patients with\nadvanced gallbladder or bile duct cancers, and is still a highly invasive surgical\nprocedure. Feasibility of this invasive procedure for biliary cancers has not fully\ninvastigated.\nAims & Methods: The aim of this study is to review surgical outcome of HPD in\nterms of case series of a single surgeon at three Japanese tertiary referral centers.\nConsecutive one hundred one hepatobiliary resections with caudate lobectomy\nwere carried out by a single surgeon (TS) at National Cancer Center, Tokyo,\nAichi Cancer Center, Nagoya, and Aichi Medical University, Nagakute since\n2002 and 2016. Of these 14 included 13 patients with bile duct cancer and one\nwith gallbladder cancer underwent HPD were analyzed. Essentially, liver transection\nwas performed in terms of Pean clamp crushing method under intermittent\ninflow occlusion and pancreatojujunostomy was carried out in terms of duct to\nmucosa anastomosis.\nResults: There were 9 men and 5 women. The median age was 66 years old (34–\n81). All patients underwent preoperative biliary drainage and 12 patients underwent\npreoperative portal vein embolization. As to the extent of liver resection,\nleft hemihepatectomy was performed in 2, right hemihepatectomy in 11, and\nright trisectionectomy in 1 patient, respectively. Combined portal vein resection\nand reconstruction was carried out in 6 (42.9%), and hepatic arterial resection\nand reconstruction in one patients (7.1%). The median operation time was 822\nminutes (518–992), and the median intraoperative blood loss was 1716 ml (730–\n2930), respectively. Although one patient underwent left trisectionectomy with\nsegmental portal vein resection and reconstruction of 101 hepatobiliary resections\nresulted in the postoperative mortality (mortality rate 1.0%), HPD was\naccomplished with zero mortality in this studied period. Histologically, the proximal\nbile duct margins were confirmed positive for cancer cells in two patients\nwith bile duct cancer (R1 resection). Four patients with bile duct cancer survived\nmore than 5 years without evidence of tumor recurrence, on the other hand one\npatient with gallbladder cancer died from recurrence 7 months after the surgery.\nConclusion: HPD may become a safe and potentially feasible surgical procedure\nfor bile duct cancer, the indication of HPD for gallbladder cancer should be\nelucidated for further investigations in terms of large case series. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"outcomes surgical resection gallbladder cancer patients presenting jaundice systematic review meta analysis introduction preoperative jaundice considered relative contraindication radical gallbladder cancer gbc resection due poor prognosis high postoperative morbidity recent reports indicated aggressive surgery may improve long term survival patients advanced gbc present obstructive jaundice current systematic review meta analysis aimed compare postoperative outcomes among jaundiced non jaundiced patients resectable gbc methods electronic search performed using several medical subject headings terms cholecyst gallbladder tumor cancer carcinoma adenocarcinoma neoplasia neoplasm jaundice icterus overall survival surgery primary outcome resectability postoperative morbidity secondary outcomes results overall survival shorter among patients presented jaundice hazard ratio hr 2 21 95 confidence interval ci 1 64 2 97 p 0 001 patients jaundice less likely resectable disease odds ratio 0 27 95 ci 0 17 0 43 p 0 001 jaundice group higher odds postoperative morbidity bile leak posthepatectomy failure versus non jaundiced control group conclusions radical surgery gbc resection patients presenting obstructive jaundice associated reduced overall survival increased postoperative morbidity jaundiced patients advanced gbc considered surgical resection need careful evaluation counseling undertaking extensive surgical resection pubmed","probabilities":0.9799733,"Title":"Outcomes of surgical resection of gallbladder cancer in patients presenting with jaundice: A systematic review and meta-analysis","Abstract":"INTRODUCTION: Preoperative jaundice is considered a relative contraindication to radical gallbladder cancer (GBC) resection due to poor prognosis and high postoperative morbidity. Recent reports have indicated that aggressive surgery may improve long-term survival for patients with advanced GBC who present with obstructive jaundice. The current systematic review and meta-analysis aimed to compare postoperative outcomes among jaundiced and non-jaundiced patients with resectable GBC. METHODS: An electronic search was performed using several Medical Subject Headings terms: cholecyst, gallbladder, tumor, cancer, carcinoma, adenocarcinoma, neoplasia, neoplasm, jaundice, and icterus. Overall survival after surgery was the primary outcome; resectability and postoperative morbidity were the secondary outcomes. RESULTS: Overall survival was shorter among patients who presented with jaundice (Hazard ratio [HR]: 2.21, 95% confidence interval [CI], 1.64-2.97; P < 0.001). Patients with jaundice were less likely to have resectable disease (odds ratio: 0.27, 95% CI, 0.17-0.43; P < 0.001). The jaundice group had higher odds of postoperative morbidity, bile-leak, and posthepatectomy failure versus the non-jaundiced control group. CONCLUSIONS: Radical surgery for GBC resection for patients presenting with obstructive jaundice was associated with reduced overall survival and increased postoperative morbidity. Jaundiced patients with advanced GBC should be considered for surgical resection but need careful evaluation and counseling before undertaking extensive surgical resection.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes of surgical resection of gallbladder cancer in patients presenting with jaundice: A systematic review and meta-analysis INTRODUCTION: Preoperative jaundice is considered a relative contraindication to radical gallbladder cancer (GBC) resection due to poor prognosis and high postoperative morbidity. Recent reports have indicated that aggressive surgery may improve long-term survival for patients with advanced GBC who present with obstructive jaundice. The current systematic review and meta-analysis aimed to compare postoperative outcomes among jaundiced and non-jaundiced patients with resectable GBC. METHODS: An electronic search was performed using several Medical Subject Headings terms: cholecyst, gallbladder, tumor, cancer, carcinoma, adenocarcinoma, neoplasia, neoplasm, jaundice, and icterus. Overall survival after surgery was the primary outcome; resectability and postoperative morbidity were the secondary outcomes. RESULTS: Overall survival was shorter among patients who presented with jaundice (Hazard ratio [HR]: 2.21, 95% confidence interval [CI], 1.64-2.97; P < 0.001). Patients with jaundice were less likely to have resectable disease (odds ratio: 0.27, 95% CI, 0.17-0.43; P < 0.001). The jaundice group had higher odds of postoperative morbidity, bile-leak, and posthepatectomy failure versus the non-jaundiced control group. CONCLUSIONS: Radical surgery for GBC resection for patients presenting with obstructive jaundice was associated with reduced overall survival and increased postoperative morbidity. Jaundiced patients with advanced GBC should be considered for surgical resection but need careful evaluation and counseling before undertaking extensive surgical resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"demographics tumor characteristics treatment clinical outcomes patients ampullary cancer surveillance epidemiology end results seer cohort study background ampullary cancer accounts 0 2 gastrointestinal cancers objective study investigate incidence demographics tumor characteristics treatment survival patients ampullary tumors methods data ampullary cancer 2004 2013 extracted surveillance epidemiology end results seer registry clinical epidemiology tumors analyzed using seer stat results total 6803 patients ampullary cancer identified median age diagnosis 71 13 years overall age adjusted incidence ampullary cancer 0 59 per 100 000 per year higher incidence ampullary cancer observed males compared females 0 74 vs 0 48 per 100 000 per year tumors moderately differentiated 39 5 common stage presentation stage 21 followed stage ii 20 majority 63 tumors surgically resected 20 patients received radiotherapy one 5 year cause specific survival ampullary cancer 71 7 38 8 respectively median survival 31 months cox regression analysis black race increasing cancer stage grade n1 stage non surgical treatment associated poorer prognosis treated surgical intervention 4 5 times increased risk death hazard ratio 4 5 95 ci 3 93 5 09 p 0 000 conclusions annual incidence ampullary cancer fairly constant though males likely affected incidence increases age patients treated surgical intervention significantly better outcomes additionally use endoscopic techniques ampullary cancer detected treated much earlier pubmed","probabilities":0.9799733,"Title":"Demographics, tumor characteristics, treatment, and clinical outcomes of patients with ampullary cancer: a Surveillance, Epidemiology, and End Results (SEER) cohort study","Abstract":"BACKGROUND: Ampullary cancer accounts for only 0.2% of gastrointestinal cancers. The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with ampullary tumors. METHODS: Data on ampullary cancer between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results (SEER) Registry. The clinical epidemiology of these tumors was analyzed using SEER*Stat. RESULTS: A total of 6803 patients with ampullary cancer were identified. Median age at diagnosis was 71±13 years. The overall age-adjusted incidence of ampullary cancer was 0.59 per 100,000 per year. A higher incidence of ampullary cancer was observed in males compared to females (0.74 vs. 0.48 per 100,000 per year). Most tumors were moderately differentiated (39.5%). The most common stage at presentation was Stage I (21%), followed by Stage II (20%). The majority (63%) of these tumors were surgically resected while 20% of patients received radiotherapy. One and 5-year cause-specific survival for ampullary cancer was 71.7% and 38.8% respectively, with a median survival of 31 months. On Cox regression analysis, black race, increasing cancer stage and grade, N1 stage, and non-surgical treatment were associated with poorer prognosis. Those who were not treated with surgical intervention were at 4.5 times increased risk for death (hazard ratio 4.5, 95% CI: 3.93-5.09, P=0.000). CONCLUSIONS: The annual incidence of ampullary cancer has been fairly constant, though males are more likely to be affected. While its incidence increases with age, patients who are treated by surgical intervention have significantly better outcomes. Additionally, through the use of endoscopic techniques, ampullary cancer can be detected and treated much earlier.","Source":"PubMed","category":"HUMAN","training_data":"Demographics, tumor characteristics, treatment, and clinical outcomes of patients with ampullary cancer: a Surveillance, Epidemiology, and End Results (SEER) cohort study BACKGROUND: Ampullary cancer accounts for only 0.2% of gastrointestinal cancers. The objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with ampullary tumors. METHODS: Data on ampullary cancer between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results (SEER) Registry. The clinical epidemiology of these tumors was analyzed using SEER*Stat. RESULTS: A total of 6803 patients with ampullary cancer were identified. Median age at diagnosis was 71±13 years. The overall age-adjusted incidence of ampullary cancer was 0.59 per 100,000 per year. A higher incidence of ampullary cancer was observed in males compared to females (0.74 vs. 0.48 per 100,000 per year). Most tumors were moderately differentiated (39.5%). The most common stage at presentation was Stage I (21%), followed by Stage II (20%). The majority (63%) of these tumors were surgically resected while 20% of patients received radiotherapy. One and 5-year cause-specific survival for ampullary cancer was 71.7% and 38.8% respectively, with a median survival of 31 months. On Cox regression analysis, black race, increasing cancer stage and grade, N1 stage, and non-surgical treatment were associated with poorer prognosis. Those who were not treated with surgical intervention were at 4.5 times increased risk for death (hazard ratio 4.5, 95% CI: 3.93-5.09, P=0.000). CONCLUSIONS: The annual incidence of ampullary cancer has been fairly constant, though males are more likely to be affected. While its incidence increases with age, patients who are treated by surgical intervention have significantly better outcomes. Additionally, through the use of endoscopic techniques, ampullary cancer can be detected and treated much earlier. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder cancer laparoscopic cholecystectomy incidence management prognosis aims although incidental gallbladder cancer igbc diagnosed laparoscopic cholecystectomy lc rare incidence management prognosis still unclear controversial present study aimed increase understanding igbc lc medical community methods patients igbc treated institution january 2001 december 2018 enrolled data collected included demographic characteristics treatment pattern pathological information prognoses compared characteristics patients different prognoses calculated cumulative overall survival rate mean survival period igbc results cohort comprised 26 patients mean age 66 4 12 5 years patients diagnosed igbc via postoperative pathology three patients underwent radical reoperation june 2019 26 patients followed mean 31 6 29 6 months fourteen patients died follow period 12 survived without recurrence mean survival duration 50 5 months 1 3 5 year cumulative overall survival rates entire cohort 79 8 49 0 40 8 respectively igbc patients t1a stage significantly longer survival t1b advanced stages 96 1 vs 32 6 months p 006 conclusions igbc lc diagnosed 0 2 patients accounting 5 4 gallbladder cancer cases igbc patients t1a stage significantly longer survival t1b advanced stages simple cholecystectomy probably acceptable t1a lesions stn","probabilities":0.9799733,"Title":"Incidental Gallbladder Cancer After Laparoscopic Cholecystectomy: Incidence Management And Prognosis","Abstract":"Aims: Although incidental gallbladder cancer (IGBC) diagnosed after laparoscopic cholecystectomy (LC) is not rare, its incidence, management, and prognosis are still unclear and controversial. The present study aimed to increase the understanding of IGBC after LC in the medical community. \n\n Methods: Patients with IGBC treated at our institution between January 2001 and December 2018 were enrolled. Data collected included demographic characteristics, treatment pattern, pathological information, and prognoses. We compared the characteristics of patients with different prognoses and calculated the cumulative overall survival rate and mean survival period for IGBC. \n\n Results: The cohort comprised 26 patients with a mean age of 66.4 ± 12.5 years. All patients were diagnosed with IGBC via postoperative pathology. Three patients underwent radical reoperation. As of June 2019, 26 patients were followed for a mean of 31.6 ± 29.6 months. Fourteen patients died during the follow-up period, and 12 survived without recurrence. The mean survival duration was 50.5 months. The 1-, 3-, and 5-year cumulative overall survival rates of the entire cohort were 79.8, 49.0, and 40.8%, respectively. IGBC patients with T1a stage had significantly longer survival than those with T1b or more advanced stages (96.1 vs 32.6 months, P = .006). \n\n Conclusions: IGBC after LC is diagnosed in 0.2% of patients, accounting for 5.4% of all gallbladder cancer cases. IGBC patients with T1a stage had significantly longer survival than those with T1b or more advanced stages. Simple cholecystectomy is probably acceptable only in T1a lesions.","Source":"STN","category":"HUMAN","training_data":"Incidental Gallbladder Cancer After Laparoscopic Cholecystectomy: Incidence Management And Prognosis Aims: Although incidental gallbladder cancer (IGBC) diagnosed after laparoscopic cholecystectomy (LC) is not rare, its incidence, management, and prognosis are still unclear and controversial. The present study aimed to increase the understanding of IGBC after LC in the medical community. \n\n Methods: Patients with IGBC treated at our institution between January 2001 and December 2018 were enrolled. Data collected included demographic characteristics, treatment pattern, pathological information, and prognoses. We compared the characteristics of patients with different prognoses and calculated the cumulative overall survival rate and mean survival period for IGBC. \n\n Results: The cohort comprised 26 patients with a mean age of 66.4 ± 12.5 years. All patients were diagnosed with IGBC via postoperative pathology. Three patients underwent radical reoperation. As of June 2019, 26 patients were followed for a mean of 31.6 ± 29.6 months. Fourteen patients died during the follow-up period, and 12 survived without recurrence. The mean survival duration was 50.5 months. The 1-, 3-, and 5-year cumulative overall survival rates of the entire cohort were 79.8, 49.0, and 40.8%, respectively. IGBC patients with T1a stage had significantly longer survival than those with T1b or more advanced stages (96.1 vs 32.6 months, P = .006). \n\n Conclusions: IGBC after LC is diagnosed in 0.2% of patients, accounting for 5.4% of all gallbladder cancer cases. IGBC patients with T1a stage had significantly longer survival than those with T1b or more advanced stages. Simple cholecystectomy is probably acceptable only in T1a lesions. STN","prediction_labels":"HUMAN"},{"cleaned":"pre operative sarcopenia identifies patients risk poor survival resection biliary tract cancers introduction biliary tract cancers btc aggressive malignancies require complex surgical procedures patients btc present skeletal muscle depletion yet effects muscle wasting sarcopenia outcomes well studied objective current study define impact sarcopenia survival among patients undergoing resection btc methods patients underwent exploration btc pre operative ct scan available review identified body composition variables including total psoas muscle area cm 2 muscle density hounsfield units visceral fat area subcutaneous fat area waist hip ratio analyzed level l3 outcomes assessed according presence absence sarcopenia defined using sex bmi specific threshold values psoas muscle index pmi cm 2 m 2 results among 117 patients btc 78 67 underwent curative intent resection 39 33 explored undergo resection due metastatic locally advanced disease tumor type included distal cholangiocarcinoma n 18 15 4 hilar cholangiocarcinoma n 27 23 1 gallbladder carcinoma n 52 44 4 intrahepatic cholangiocarcinoma n 20 17 1 median patient age 65 6 years 43 6 male mean patient bmi 26 1 kg m 2 among men 27 5 kg m 2 among women overall 41 35 0 patients sarcopenia sarcopenia associated increased risk death among patients underwent resection hr 3 52 95 ci 1 60 7 78 p 0 002 comparable patients unresectable metastatic disease factors low serum albumin hr 3 17 95 ci 1 30 7 74 p 0 011 low psoas density hr 2 96 95 ci 1 21 7 21 p 0 017 also associated increased risk death survival stratified based sarcopenia psoas density serum albumin presence variable associated incremental increased risk death 0 variables ref 1 variable hr 3 8 95 ci 1 0 14 p 0 043 2 variables hr 13 1 95 ci 3 0 57 7 p 0 001 3 variables hr 14 6 95 ci 2 5 87 1 p 0 003 patients adverse prognostic factors 3 year os 67 versus survival among patients 3 factors conclusions sarcopenia common among patients undergoing resection btc occurring 1 every 3 patients sarcopenia associated poor survival resection particularly among patients experienced recurrence body composition metrics sarcopenia low psoas muscle density addition low albumin level able stratify patients different prognostic categories pubmed","probabilities":0.9799733,"Title":"Pre-operative Sarcopenia Identifies Patients at Risk for Poor Survival After Resection of Biliary Tract Cancers","Abstract":"INTRODUCTION: Biliary tract cancers (BTC) are aggressive malignancies that require complex surgical procedures. Patients with BTC can present with skeletal muscle depletion, yet the effects of muscle wasting (sarcopenia) on outcomes have not been well studied. The objective of the current study was to define the impact of sarcopenia on survival among patients undergoing resection of BTC. METHODS: Patients who underwent exploration for BTC who had a pre-operative CT scan available for review were identified. Body composition variables including total and psoas muscle area (cm(2)), muscle density (Hounsfield units), visceral fat area, subcutaneous fat area, and waist-to-hip ratio were analyzed at the level of L3. Outcomes were assessed according to the presence or absence of sarcopenia defined using sex- and BMI-specific threshold values for Psoas Muscle Index (PMI, cm(2)/m(2)). RESULTS: Among 117 patients with BTC, 78 (67%) underwent curative-intent resection and 39 (33%) were explored but did not undergo resection due to metastatic/locally advanced disease. Tumor type included distal cholangiocarcinoma (n = 18, 15.4%), hilar cholangiocarcinoma (n = 27, 23.1%), gallbladder carcinoma (n = 52, 44.4%), and intrahepatic cholangiocarcinoma (n = 20, 17.1%). Median patient age was 65.6 years and 43.6% were male. Mean patient BMI was 26.1 kg/m(2) among men and 27.5 kg/m(2) among women. Overall, 41 (35.0%) patients had sarcopenia. Sarcopenia was associated with an increased risk of death among patients who underwent resection (HR 3.52, 95%CI 1.60-7.78, p = 0.002), which was comparable to patients with unresectable metastatic disease. Other factors such as low serum albumin (HR 3.17, 95% CI 1.30-7.74, p = 0.011) and low psoas density (HR 2.96, 95% CI 1.21-7.21, p = 0.017) were also associated with increased risk of death. Survival was stratified based on sarcopenia, psoas density, and serum albumin. The presence of each variable was associated with an incremental increased risk of death (0 variables ref.; 1 variable HR 3.8, 95% CI 1.0-14, p = 0.043; 2 variables HR 13.1, 95% CI 3.0-57.7, p = 0.001; 3 variables HR 14.6, 95% CI 2.5-87.1, p = 0.003). Patients who had no adverse prognostic factors had a 3-year OS of 67% versus no survival among patients with all 3 factors. CONCLUSIONS: Sarcopenia was common among patients undergoing resection of BTC, occurring in 1 of every 3 patients. Sarcopenia was associated with poor survival after resection, particularly among patients who experienced a recurrence. Body composition metrics such as sarcopenia and low psoas muscle density in addition to low albumin level were able to stratify patients into different prognostic categories.","Source":"PubMed","category":"HUMAN","training_data":"Pre-operative Sarcopenia Identifies Patients at Risk for Poor Survival After Resection of Biliary Tract Cancers INTRODUCTION: Biliary tract cancers (BTC) are aggressive malignancies that require complex surgical procedures. Patients with BTC can present with skeletal muscle depletion, yet the effects of muscle wasting (sarcopenia) on outcomes have not been well studied. The objective of the current study was to define the impact of sarcopenia on survival among patients undergoing resection of BTC. METHODS: Patients who underwent exploration for BTC who had a pre-operative CT scan available for review were identified. Body composition variables including total and psoas muscle area (cm(2)), muscle density (Hounsfield units), visceral fat area, subcutaneous fat area, and waist-to-hip ratio were analyzed at the level of L3. Outcomes were assessed according to the presence or absence of sarcopenia defined using sex- and BMI-specific threshold values for Psoas Muscle Index (PMI, cm(2)/m(2)). RESULTS: Among 117 patients with BTC, 78 (67%) underwent curative-intent resection and 39 (33%) were explored but did not undergo resection due to metastatic/locally advanced disease. Tumor type included distal cholangiocarcinoma (n = 18, 15.4%), hilar cholangiocarcinoma (n = 27, 23.1%), gallbladder carcinoma (n = 52, 44.4%), and intrahepatic cholangiocarcinoma (n = 20, 17.1%). Median patient age was 65.6 years and 43.6% were male. Mean patient BMI was 26.1 kg/m(2) among men and 27.5 kg/m(2) among women. Overall, 41 (35.0%) patients had sarcopenia. Sarcopenia was associated with an increased risk of death among patients who underwent resection (HR 3.52, 95%CI 1.60-7.78, p = 0.002), which was comparable to patients with unresectable metastatic disease. Other factors such as low serum albumin (HR 3.17, 95% CI 1.30-7.74, p = 0.011) and low psoas density (HR 2.96, 95% CI 1.21-7.21, p = 0.017) were also associated with increased risk of death. Survival was stratified based on sarcopenia, psoas density, and serum albumin. The presence of each variable was associated with an incremental increased risk of death (0 variables ref.; 1 variable HR 3.8, 95% CI 1.0-14, p = 0.043; 2 variables HR 13.1, 95% CI 3.0-57.7, p = 0.001; 3 variables HR 14.6, 95% CI 2.5-87.1, p = 0.003). Patients who had no adverse prognostic factors had a 3-year OS of 67% versus no survival among patients with all 3 factors. CONCLUSIONS: Sarcopenia was common among patients undergoing resection of BTC, occurring in 1 of every 3 patients. Sarcopenia was associated with poor survival after resection, particularly among patients who experienced a recurrence. Body composition metrics such as sarcopenia and low psoas muscle density in addition to low albumin level were able to stratify patients into different prognostic categories. PubMed","prediction_labels":"HUMAN"},{"cleaned":"obesity cholangiocarcinoma estimated half population developed countries either overweight obese developing nations obesity rates increased surpass seen western countries rate increase obesity many implications obesity associated numerous negative health effects including increased risks hypertension diabetes cardiovascular disease stroke liver disease apnea cancer types obesity considered one major public health concerns facing society cholangiocarcinomas bile duct cancers malignant tumors arising cholangiocytes inside outside liver although cholangiocarcinomas relatively rare highly lethal low survival rate associated cholangiocarcinoma due advanced stage disease time diagnosis prevention therefore especially important cancer type data suggest incidence cholangiocarcinoma western world rise increasing rate obesity may one factors responsible increase determining whether obesity risk factor cholangiocarcinoma significant clinical societal implications obesity prevalent modifiable paper seeks provide summary current knowledge linking obesity cholangiocarcinoma encourage research topic pubmed","probabilities":0.9799733,"Title":"Obesity and cholangiocarcinoma","Abstract":"It is estimated that about half of the population in developed countries are either overweight or obese. In some developing nations obesity rates have increased to surpass those seen in Western countries. This rate increase in obesity has many implications as obesity has been associated with numerous negative health effects including increased risks of hypertension, diabetes, cardiovascular disease, stroke, liver disease, apnea, and some cancer types. Obesity is now considered to be one of the major public health concerns facing the society. Cholangiocarcinomas (bile duct cancers) are malignant tumors arising from cholangiocytes inside or outside of the liver. Although cholangiocarcinomas are relatively rare, they are highly lethal. The low survival rate associated with cholangiocarcinoma is due to the advanced stage of the disease at the time of diagnosis. Prevention is therefore especially important in this cancer type. Some data suggest that the incidence of cholangiocarcinoma in the western world is on the rise. Increasing rate of obesity may be one of the factors responsible for this increase. Determining whether obesity is a risk factor for cholangiocarcinoma has significant clinical and societal implications as obesity is both prevalent and modifiable. This paper seeks to provide a summary of the current knowledge linking obesity and cholangiocarcinoma, and encourage further research on this topic.","Source":"PubMed","category":"HUMAN","training_data":"Obesity and cholangiocarcinoma It is estimated that about half of the population in developed countries are either overweight or obese. In some developing nations obesity rates have increased to surpass those seen in Western countries. This rate increase in obesity has many implications as obesity has been associated with numerous negative health effects including increased risks of hypertension, diabetes, cardiovascular disease, stroke, liver disease, apnea, and some cancer types. Obesity is now considered to be one of the major public health concerns facing the society. Cholangiocarcinomas (bile duct cancers) are malignant tumors arising from cholangiocytes inside or outside of the liver. Although cholangiocarcinomas are relatively rare, they are highly lethal. The low survival rate associated with cholangiocarcinoma is due to the advanced stage of the disease at the time of diagnosis. Prevention is therefore especially important in this cancer type. Some data suggest that the incidence of cholangiocarcinoma in the western world is on the rise. Increasing rate of obesity may be one of the factors responsible for this increase. Determining whether obesity is a risk factor for cholangiocarcinoma has significant clinical and societal implications as obesity is both prevalent and modifiable. This paper seeks to provide a summary of the current knowledge linking obesity and cholangiocarcinoma, and encourage further research on this topic. PubMed","prediction_labels":"HUMAN"},{"cleaned":"evaluation surgical resection gallbladder carcinoma japanese cancer institute background aims surgical resection radical treatment option gallbladder carcinoma gbc however still difficult cure patient prognosis poor assessment surgical results chemotherapy options may elucidate effective treatments methodology retrospectively examined demographics surgical records outcome 33 patients gbc undergoing surgical resection results postoperative cancer recurrence observed 36 patients mean cancer free survival time 84 months 3 year cancer free survival rate 70 mean overall survival time 96 months 5 year overall survival rate 52 3 year cancer free survival 5 year overall survival significantly different final tumor stages p 0 001 higher cea ca19 9 level significantly related poor overall survival p 0 05 macroscopically papillary type tumor showed significantly better overall survival compared nodular flat types p 0 05 degree invasion node metastasis moderate poor differentiation vascular perineural invasion invasion liver hepatoduodenal ligament significantly associated poor overall survival p 0 05 cancerfree margin hepatic cut end dissected periductal structures showed significantly poor prognosis p 0 05 overall survival final curability significantly associated better curability b c p 0 05 conclusions radically extended surgical resection gbc necessary obtain improved patient survival new adjuvant chemotherapy expected improve results surgery pubmed","probabilities":0.9799733,"Title":"Evaluation of surgical resection for gallbladder carcinoma at a Japanese cancer institute","Abstract":"BACKGROUND/AIMS: Surgical resection is a radical treatment option for gallbladder carcinoma (GBC); however, it is still difficult to cure and patient prognosis is poor. An assessment of the surgical results and chemotherapy options may elucidate effective treatments. METHODOLOGY: We retrospectively examined the demographics, surgical records and outcome in 33 patients with GBC undergoing surgical resection. RESULTS: Postoperative cancer recurrence was observed in 36% of patients. Mean cancer-free survival time was 84 months and 3-year cancer-free survival rate was 70% Mean overall survival time was 96 months and 5-year overall survival rate was 52%. The 3-year cancer-free survival and the 5-year overall survival were significantly different between the final tumor stages (p<0.001). Higher CEA and CA19- 9 level were significantly related to poor overall survival (p<0.05). Macroscopically, papillary type tumor showed significantly better overall survival compared to nodular or flat types (p<0.05). Degree of invasion, node metastasis, moderate or poor differentiation, vascular or perineural invasion and invasion of the liver or hepatoduodenal ligament were significantly associated with poor overall survival (p<0.05). A cancerfree margin at the hepatic cut end and dissected periductal structures showed a significantly poor prognosis (p<0.05). The overall survival in final curability A was significantly associated with better curability than B or C (p<0.05). CONCLUSIONS: Radically extended surgical resection for GBC is necessary to obtain improved patient survival and new adjuvant chemotherapy would be expected to improve results after surgery.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of surgical resection for gallbladder carcinoma at a Japanese cancer institute BACKGROUND/AIMS: Surgical resection is a radical treatment option for gallbladder carcinoma (GBC); however, it is still difficult to cure and patient prognosis is poor. An assessment of the surgical results and chemotherapy options may elucidate effective treatments. METHODOLOGY: We retrospectively examined the demographics, surgical records and outcome in 33 patients with GBC undergoing surgical resection. RESULTS: Postoperative cancer recurrence was observed in 36% of patients. Mean cancer-free survival time was 84 months and 3-year cancer-free survival rate was 70% Mean overall survival time was 96 months and 5-year overall survival rate was 52%. The 3-year cancer-free survival and the 5-year overall survival were significantly different between the final tumor stages (p<0.001). Higher CEA and CA19- 9 level were significantly related to poor overall survival (p<0.05). Macroscopically, papillary type tumor showed significantly better overall survival compared to nodular or flat types (p<0.05). Degree of invasion, node metastasis, moderate or poor differentiation, vascular or perineural invasion and invasion of the liver or hepatoduodenal ligament were significantly associated with poor overall survival (p<0.05). A cancerfree margin at the hepatic cut end and dissected periductal structures showed a significantly poor prognosis (p<0.05). The overall survival in final curability A was significantly associated with better curability than B or C (p<0.05). CONCLUSIONS: Radically extended surgical resection for GBC is necessary to obtain improved patient survival and new adjuvant chemotherapy would be expected to improve results after surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival patients gallbladder carcinoma last 13 years better population based study introduction cancer screening surgical improvement increased steadily recent years leading improvement survival cancers aims study investigate trend survival time patients gallbladder carcinoma using large population based study methods surveillance epidemiology end results seer cancer registry utilized identify patients histologically diagnosed gallbladder carcinoma 2000 2013 kaplan meier analysis used compare differences carcinoma specific survival 2000 2007 2008 2013 results total 414 patients identified study analysis including 185 patients 2000 2007 229 patients 2008 2013 mean age entire study cohort 66 9 years sem 0 632 range 28 96 80 white 10 black 10 36 male staging available 174 42 pts demonstrated 8 stage 36 stage ii 53 stage iii 3 stage iv tumors significant difference age race grade localized regional distal extension time periods p 0 05 treatment entire cohort included primary site surgery 25 radiation form 7 9 surgery plus radiation 6 9 neither 60 proportion patients undergoing treatment either surgery radiation significantly different two study periods p 0 011 15 absolute increase patients undergo either surgery radiation kaplan meier analysis revealed significant differences survival 2000 2007 6 month survival 46 12 month survival 34 2008 2013 time periods 6 month survival 48 12 month survival 28 log rank p 0 930 figure 1 significant differences survival last 13 years every year considered individually p 0 05 conclusion significant difference gallbladder carcinoma specific survival last 13 years despite improvements treatment strategies surgical techniques gallbladder carcinoma unfortunately continues present high mortality patients afflicted disease google scholar","probabilities":0.9799733,"Title":"Survival In Patients With Gallbladder Carcinoma Over Last 13 Years: Are We Doing Any Better? A Population Based Study","Abstract":"Introduction: Cancer screening and surgical improvement have increased steadily over recent years leading to improvement in the survival in most cancers. The aims of this study was to investigate the trend in the survival over time in patients with gallbladder carcinoma using a large population-based study.\nMethods: The Surveillance Epidemiology & End Results (SEER) Cancer registry was utilized to identify patients with histologically diagnosed gallbladder carcinoma between 2000 and 2013. Kaplan-Meier analysis was used to compare differences in carcinoma-specific survival between 2000-2007 and 2008-2013.\nResults: A total of 414 patients were identified for the study analysis, including 185 patients in 2000-2007 & 229 patients in 2008-2013. The mean age of the entire study cohort was 66.9 years (SEM: 0.632, range: 28-96), 80% white (10% black, 10% other) & 36% male. Staging was available in 174 (42%) pts, which demonstrated 8% in stage I, 36% in stage II, 53% in stage III & 3% in stage IV tumors. There was no significant difference in age, race, grade or localized/regional/distal extension between the time periods (all P>0.05). Treatment for the entire cohort included primary site surgery only (25%), radiation only (any form; 7.9%), surgery plus radiation (6.9%) or neither (60%). The proportion of patients undergoing treatment with either surgery or radiation was significantly different between the two study periods (P=0.011) with a 15% absolute increase in patients who did not undergo either surgery or radiation. Kaplan-Meier analysis revealed no significant differences in survival between 2000-2007 (6-month survival: 46%; 12-month survival: 34%) and 2008-2013 time periods (6-month survival: 48%; 12-month survival: 28%; log-rank: P=0.930) (figure 1). There were no significant differences in survival in last 13 years when every year was considered individually (all p>0.05).\nConclusion: There was no significant difference in the gallbladder carcinoma-specific survival in the last 13 years. Despite improvements in treatment strategies and surgical techniques, gallbladder carcinoma unfortunately continues to present with high mortality in patients afflicted with the disease.","Source":"Google Scholar","category":"HUMAN","training_data":"Survival In Patients With Gallbladder Carcinoma Over Last 13 Years: Are We Doing Any Better? A Population Based Study Introduction: Cancer screening and surgical improvement have increased steadily over recent years leading to improvement in the survival in most cancers. The aims of this study was to investigate the trend in the survival over time in patients with gallbladder carcinoma using a large population-based study.\nMethods: The Surveillance Epidemiology & End Results (SEER) Cancer registry was utilized to identify patients with histologically diagnosed gallbladder carcinoma between 2000 and 2013. Kaplan-Meier analysis was used to compare differences in carcinoma-specific survival between 2000-2007 and 2008-2013.\nResults: A total of 414 patients were identified for the study analysis, including 185 patients in 2000-2007 & 229 patients in 2008-2013. The mean age of the entire study cohort was 66.9 years (SEM: 0.632, range: 28-96), 80% white (10% black, 10% other) & 36% male. Staging was available in 174 (42%) pts, which demonstrated 8% in stage I, 36% in stage II, 53% in stage III & 3% in stage IV tumors. There was no significant difference in age, race, grade or localized/regional/distal extension between the time periods (all P>0.05). Treatment for the entire cohort included primary site surgery only (25%), radiation only (any form; 7.9%), surgery plus radiation (6.9%) or neither (60%). The proportion of patients undergoing treatment with either surgery or radiation was significantly different between the two study periods (P=0.011) with a 15% absolute increase in patients who did not undergo either surgery or radiation. Kaplan-Meier analysis revealed no significant differences in survival between 2000-2007 (6-month survival: 46%; 12-month survival: 34%) and 2008-2013 time periods (6-month survival: 48%; 12-month survival: 28%; log-rank: P=0.930) (figure 1). There were no significant differences in survival in last 13 years when every year was considered individually (all p>0.05).\nConclusion: There was no significant difference in the gallbladder carcinoma-specific survival in the last 13 years. Despite improvements in treatment strategies and surgical techniques, gallbladder carcinoma unfortunately continues to present with high mortality in patients afflicted with the disease. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder cancer diagnosed cholecystectomy specimens study 30 cases background gallbladder cancer rare cancer poor prognosis association gallstone disease main risk factor cancer aim describe demographics clinic pathologic therapeutic management incidentally gallbladder cancer diagnosed cholecystectomy specimens methods retrospective study including 30 cases gallbladder cancer incidentally detected cholecystectomy specimens results incidence gallbladder cancer incidentally discovered 0 83 sex ratio m f 0 5 average age 68 years main risk factor cholelithiasis 38 adenocarcinoma frequent histological type found 86 6 cases biliary type 56 6 cases 76 7 tumors classified early stages stages 0 ii 23 3 advanced stages iii iv simple cholecystectomy curative 66 7 cases overall survival rate 56 7 one year best survival rate early stages 100 stages 0 45 4 stage ii conclusions gallbladder cancer poor prognosis late diagnosis thorough sampling careful attention histological examination parts cholecystectomy specimens allows detection early cancer better prognosis pubmed","probabilities":0.9799733,"Title":"Incidental gallbladder cancer diagnosed on cholecystectomy specimens: a study of 30 cases","Abstract":"Background - The gallbladder cancer is a rare cancer with poor prognosis. The association with gallstone disease is the main risk factor of this cancer. Aim - Describe the demographics, clinic-pathologic and therapeutic management of incidentally gallbladder cancer diagnosed on cholecystectomy specimens. Methods - retrospective study including 30 cases of gallbladder cancer incidentally detected on cholecystectomy specimens. Results - The incidence of gallbladder cancer incidentally discovered was 0.83%. The sex ratio M/F was 0.5 and the average age was 68 years. The main risk factor was cholelithiasis (38%). Adenocarcinoma was the most frequent histological type found in 86.6% of cases and it was biliary-type in 56.6% of cases. 76,7% of the tumors were classified in early stages (stages 0, I and II) and 23,3% were in advanced stages (III and IV). A simple cholecystectomy was curative in 66.7% of cases. Overall survival rate was 56.7% at one year. The best survival rate was for the early stages: 100% stages 0-I and 45.4% stage II. Conclusions - The gallbladder cancer has poor prognosis because of its late diagnosis. Thorough sampling and careful attention on histological examination of all parts of cholecystectomy specimens allows detection of early cancer with better prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Incidental gallbladder cancer diagnosed on cholecystectomy specimens: a study of 30 cases Background - The gallbladder cancer is a rare cancer with poor prognosis. The association with gallstone disease is the main risk factor of this cancer. Aim - Describe the demographics, clinic-pathologic and therapeutic management of incidentally gallbladder cancer diagnosed on cholecystectomy specimens. Methods - retrospective study including 30 cases of gallbladder cancer incidentally detected on cholecystectomy specimens. Results - The incidence of gallbladder cancer incidentally discovered was 0.83%. The sex ratio M/F was 0.5 and the average age was 68 years. The main risk factor was cholelithiasis (38%). Adenocarcinoma was the most frequent histological type found in 86.6% of cases and it was biliary-type in 56.6% of cases. 76,7% of the tumors were classified in early stages (stages 0, I and II) and 23,3% were in advanced stages (III and IV). A simple cholecystectomy was curative in 66.7% of cases. Overall survival rate was 56.7% at one year. The best survival rate was for the early stages: 100% stages 0-I and 45.4% stage II. Conclusions - The gallbladder cancer has poor prognosis because of its late diagnosis. Thorough sampling and careful attention on histological examination of all parts of cholecystectomy specimens allows detection of early cancer with better prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatopancreatoduodenectomy advanced hepatobiliary malignancies single center experience background hepatopancreatoduodenectomy complicated challenging procedure necessary curative resection advanced hepatobiliary malignancies retrospective study examine safety survival outcomes hepatopancreatoduodenectomy center methods prospectively collected data 12 patients underwent hepatopancreatoduodenectomy advanced hepatobiliary malignancies hospital january 1998 december 2014 analyzed primary endpoints treatment related morbidity mortality secondary endpoints overall survival disease free survival results curative resection achieved 11 91 7 patients complications developed 10 83 3 patients three hospital deaths resulted multiorgan failure secondary postoperative pancreatic fistula hepaticojejunostomy leakage six nine remaining patients disease recurrence nine patients median survival 39 8 5 3 151 8 months 1 3 5 year overall survival rates 66 7 55 6 27 8 respectively corresponding disease free survival rates 55 6 44 4 29 6 respectively conclusions morbidity mortality hepatopancreatoduodenectomy significant r0 resection 5 year overall survival disease free survival rates 27 8 29 6 respectively pubmed","probabilities":0.9799733,"Title":"Hepatopancreatoduodenectomy for advanced hepatobiliary malignancies: a single-center experience","Abstract":"BACKGROUND: Hepatopancreatoduodenectomy is a complicated and challenging procedure but necessary for curative resection for advanced hepatobiliary malignancies. This retrospective study was to examine the safety and survival outcomes of hepatopancreatoduodenectomy in our center. METHODS: Prospectively collected data of 12 patients who underwent hepatopancreatoduodenectomy for advanced hepatobiliary malignancies in our hospital from January 1998 to December 2014 were analyzed. The primary endpoints are treatment-related morbidity and mortality and the secondary endpoints are overall survival and disease-free survival. RESULTS: Curative resection was achieved in 11 (91.7%) patients. Complications developed in 10 (83.3%) patients. Three hospital deaths resulted from multiorgan failure secondary to postoperative pancreatic fistula or hepaticojejunostomy leakage. Six of the nine remaining patients had disease recurrence. The nine patients had a median survival of 39.8 (5.3-151.8) months. The 1-, 3- and 5-year overall survival rates were 66.7%, 55.6% and 27.8%, respectively. The corresponding disease-free survival rates were 55.6%, 44.4% and 29.6%, respectively. CONCLUSIONS: Morbidity and mortality after hepatopancreatoduodenectomy were significant. With R0 resection, the 5-year overall survival and disease-free survival rates were 27.8% and 29.6%, respectively.","Source":"PubMed","category":"HUMAN","training_data":"Hepatopancreatoduodenectomy for advanced hepatobiliary malignancies: a single-center experience BACKGROUND: Hepatopancreatoduodenectomy is a complicated and challenging procedure but necessary for curative resection for advanced hepatobiliary malignancies. This retrospective study was to examine the safety and survival outcomes of hepatopancreatoduodenectomy in our center. METHODS: Prospectively collected data of 12 patients who underwent hepatopancreatoduodenectomy for advanced hepatobiliary malignancies in our hospital from January 1998 to December 2014 were analyzed. The primary endpoints are treatment-related morbidity and mortality and the secondary endpoints are overall survival and disease-free survival. RESULTS: Curative resection was achieved in 11 (91.7%) patients. Complications developed in 10 (83.3%) patients. Three hospital deaths resulted from multiorgan failure secondary to postoperative pancreatic fistula or hepaticojejunostomy leakage. Six of the nine remaining patients had disease recurrence. The nine patients had a median survival of 39.8 (5.3-151.8) months. The 1-, 3- and 5-year overall survival rates were 66.7%, 55.6% and 27.8%, respectively. The corresponding disease-free survival rates were 55.6%, 44.4% and 29.6%, respectively. CONCLUSIONS: Morbidity and mortality after hepatopancreatoduodenectomy were significant. With R0 resection, the 5-year overall survival and disease-free survival rates were 27.8% and 29.6%, respectively. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value lymphadenectomy long term outcomes node negative intrahepatic cholangiocarcinoma multicenter study background lymphadenectomy ensures accurate staging patients intrahepatic cholangiocarcinoma especially without preoperatively suspected positive lymph nodes clinically node negative however prognostic value poorly documented aim study evaluate prognostic value lymphadenectomy long term outcomes patients undergoing surgery clinically node negative intrahepatic cholangiocarcinoma methods data patients underwent liver resection without lymphadenectomy preoperatively diagnosed intrahepatic cholangiocarcinoma 2000 2016 3 tertiary hepatobiliary centers analyzed retrospectively propensity score matching 1 1 ratio conducted based clinically relevant covariates patients clinically node negative intrahepatic cholangiocarcinoma underwent liver resection lnd group without nlnd group lymphadenectomy overall survival disease free survival compared matched cohort results among 350 patients underwent surgery study period 192 55 clinically node negative intrahepatic cholangiocarcinoma met inclusion criteria propensity score matching 2 well balanced groups 56 patients analyzed significant difference regarding postoperative variables among 112 matched patients patients underwent liver resection lymphadenectomy achieved better 3 5 year overall survival 78 65 vs 52 46 p 017 disease free survival 46 34 vs 31 31 p 042 compared patients underwent liver resection without lymphadenectomy conclusion lymphadenectomy associated better long term outcomes patients node negative intrahepatic cholangiocarcinoma data may support routine lymphadenectomy node negative intrahepatic cholangiocarcinoma objective achieving better long term outcomes pubmed","probabilities":0.9799733,"Title":"Prognostic value of lymphadenectomy for long-term outcomes in node-negative intrahepatic cholangiocarcinoma: A multicenter study","Abstract":"BACKGROUND: Lymphadenectomy ensures accurate staging for patients with intrahepatic cholangiocarcinoma, especially for those without preoperatively suspected positive lymph nodes (clinically node-negative); however, its prognostic value has been poorly documented. The aim of this study was to evaluate the prognostic value of lymphadenectomy on long-term outcomes in patients undergoing surgery for clinically node-negative intrahepatic cholangiocarcinoma. METHODS: Data from all patients who underwent liver resection with or without lymphadenectomy for preoperatively diagnosed intrahepatic cholangiocarcinoma between 2000 and 2016 at 3 tertiary hepatobiliary centers were analyzed retrospectively. Propensity score matching in a 1:1 ratio was conducted based on clinically relevant covariates between patients with clinically node-negative intrahepatic cholangiocarcinoma who underwent liver resection with (LND group) and without (NLND group) lymphadenectomy. Overall survival and disease-free survival were compared in the matched cohort. RESULTS: Among 350 patients who underwent surgery during the study period, 192 (55%) with clinically node-negative intrahepatic cholangiocarcinoma met the inclusion criteria. After propensity score matching, 2 well-balanced groups of 56 patients each were analyzed. There was no significant difference regarding postoperative variables among these 112 matched patients. Patients who underwent a liver resection with lymphadenectomy achieved better 3- and 5-year overall survival (78% and 65% vs 52% and 46%, P = .017) and disease-free survival (46% and 34% vs 31% and 31%; P = .042) compared with patients who underwent liver resection without lymphadenectomy. CONCLUSION: Lymphadenectomy can be associated with better long-term outcomes in patients with node-negative intrahepatic cholangiocarcinoma. Our data may support routine lymphadenectomy for node-negative intrahepatic cholangiocarcinoma with the objective of achieving better long-term outcomes.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic value of lymphadenectomy for long-term outcomes in node-negative intrahepatic cholangiocarcinoma: A multicenter study BACKGROUND: Lymphadenectomy ensures accurate staging for patients with intrahepatic cholangiocarcinoma, especially for those without preoperatively suspected positive lymph nodes (clinically node-negative); however, its prognostic value has been poorly documented. The aim of this study was to evaluate the prognostic value of lymphadenectomy on long-term outcomes in patients undergoing surgery for clinically node-negative intrahepatic cholangiocarcinoma. METHODS: Data from all patients who underwent liver resection with or without lymphadenectomy for preoperatively diagnosed intrahepatic cholangiocarcinoma between 2000 and 2016 at 3 tertiary hepatobiliary centers were analyzed retrospectively. Propensity score matching in a 1:1 ratio was conducted based on clinically relevant covariates between patients with clinically node-negative intrahepatic cholangiocarcinoma who underwent liver resection with (LND group) and without (NLND group) lymphadenectomy. Overall survival and disease-free survival were compared in the matched cohort. RESULTS: Among 350 patients who underwent surgery during the study period, 192 (55%) with clinically node-negative intrahepatic cholangiocarcinoma met the inclusion criteria. After propensity score matching, 2 well-balanced groups of 56 patients each were analyzed. There was no significant difference regarding postoperative variables among these 112 matched patients. Patients who underwent a liver resection with lymphadenectomy achieved better 3- and 5-year overall survival (78% and 65% vs 52% and 46%, P = .017) and disease-free survival (46% and 34% vs 31% and 31%; P = .042) compared with patients who underwent liver resection without lymphadenectomy. CONCLUSION: Lymphadenectomy can be associated with better long-term outcomes in patients with node-negative intrahepatic cholangiocarcinoma. Our data may support routine lymphadenectomy for node-negative intrahepatic cholangiocarcinoma with the objective of achieving better long-term outcomes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"rationality resectional surgery palliative interventions management patients gallbladder cancer aim present study evaluate retrospective manner survival period survival rate according stages groups r0 r1 r2 resections palliative interventions 2003 2012 67 patients diagnosed gallbladder carcinoma retrospectively analyzed patient demographics survival period survival rate according stages groups r0 r1 r2 resections palliative interventions retrospectively analyzed sixty seven patients diagnosed gallbladder carcinoma thirty eight patients 56 7 female 29 patients 43 3 male median survival period significantly longer stage ii iii diseases stage iv disease p 0 001 r0 r1 r2 resection rates patients underwent surgery curative intent 67 7 19 4 12 9 per cent respectively r0 resection rate according tumor stages 100 per cent stage 87 5 per cent stage ii 66 7 per cent stage iii 42 8 per cent stage iv disease median follow period six months eight days 36 months follow period 53 patients 79 1 died conclusion r0 resection rate decreases tumor stage increases highest survival rates r0 resection achieved patients stage ii iii diseases radical surgery benefit palliative surgery stage iv disease terms survival pubmed","probabilities":0.9799733,"Title":"The rationality of resectional surgery and palliative interventions in the management of patients with gallbladder cancer","Abstract":"The aim of the present study was to evaluate in a retrospective manner, the survival period and survival rate according to stages and groups after R0, R1, R2 resections and palliative interventions. Between 2003 and 2012, 67 patients diagnosed with gallbladder carcinoma were retrospectively analyzed. Patient demographics, the survival period, and survival rate according to stages and groups after R0, R1, R2 resections and palliative interventions were retrospectively analyzed. Sixty-seven patients were diagnosed with gallbladder carcinoma. Thirty-eight patients (56.7%) were female and 29 patients (43.3%) were male. The median survival period was significantly longer in stage II and III diseases than in stage IV disease (P < 0.001). The R0, R1, and R2 resection rates in patients who underwent surgery with curative intent were 67.7, 19.4, and 12.9 per cent, respectively. The R0 resection rate according to the tumor stages was 100 per cent for stage I, 87.5 per cent for stage II, 66.7 per cent for stage III, and 42.8 per cent for stage IV disease. The median follow-up period was six months (eight days to 36 months). During this follow-up period, 53 patients (79.1%) died. In conclusion, R0 resection rate decreases when tumor stage increases. The highest survival rates after R0 resection are achieved in patients with stage I, II, and III diseases. Radical surgery has no benefit over palliative surgery for stage IV disease in terms of survival.","Source":"PubMed","category":"HUMAN","training_data":"The rationality of resectional surgery and palliative interventions in the management of patients with gallbladder cancer The aim of the present study was to evaluate in a retrospective manner, the survival period and survival rate according to stages and groups after R0, R1, R2 resections and palliative interventions. Between 2003 and 2012, 67 patients diagnosed with gallbladder carcinoma were retrospectively analyzed. Patient demographics, the survival period, and survival rate according to stages and groups after R0, R1, R2 resections and palliative interventions were retrospectively analyzed. Sixty-seven patients were diagnosed with gallbladder carcinoma. Thirty-eight patients (56.7%) were female and 29 patients (43.3%) were male. The median survival period was significantly longer in stage II and III diseases than in stage IV disease (P < 0.001). The R0, R1, and R2 resection rates in patients who underwent surgery with curative intent were 67.7, 19.4, and 12.9 per cent, respectively. The R0 resection rate according to the tumor stages was 100 per cent for stage I, 87.5 per cent for stage II, 66.7 per cent for stage III, and 42.8 per cent for stage IV disease. The median follow-up period was six months (eight days to 36 months). During this follow-up period, 53 patients (79.1%) died. In conclusion, R0 resection rate decreases when tumor stage increases. The highest survival rates after R0 resection are achieved in patients with stage I, II, and III diseases. Radical surgery has no benefit over palliative surgery for stage IV disease in terms of survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"therapeutic targeting cdk7 suppresses tumor progression intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc lethal malignancy high mortality lack effective therapeutic targets found expression cyclin dependent kinase 7 cdk7 significantly associated higher tumor grade worse prognosis 96 icc specimens depletion cdk7 significantly inhibited cell growth induced g2 m cell cycle arrest reduced migratory invasive potential icc cells subsequent experiments demonstrated icc cells highly sensitive cdk7 inhibitor thz1 low concentration thz1 markedly inhibited cell growth cell cycle migration invasion icc cell lines rna sequencing rna seq analysis revealed thz1 treatment decreased levels massive oncogene transcripts particularly associated cell cycle cell migration quantitative reverse transcriptase pcr qrt pcr analysis confirmed transcription oncogenes involved cell cycle regulation aurka aurkb cdc25b cdk1 ccna2 mki67 c met pathway c met akt1 ptk2 crk pdpk1 arf6 selectively repressed thz1 addition thz1 exhibited significant anti tumor activity patient derived xenograft pdx model icc without causing detectable side effects stn","probabilities":0.9467213,"Title":"Therapeutic Targeting Of Cdk7 Suppresses Tumor Progression In Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy with high mortality and lack of effective therapeutic targets. Here, we found that expression of cyclin-dependent kinase 7 (CDK7) was significantly associated with higher tumor grade and worse prognosis in 96 ICC specimens. Depletion of CDK7 significantly inhibited cell growth, induced a G2/M cell cycle arrest, and reduced the migratory and invasive potential in ICC cells. Subsequent experiments demonstrated that ICC cells were highly sensitive to the CDK7 inhibitor THZ1. A low concentration of THZ1 markedly inhibited cell growth, cell cycle, migration, and invasion in ICC cell lines. RNA-sequencing (RNA-seq) analysis revealed that THZ1 treatment decreased the levels of massive oncogene transcripts, particularly those associated with cell cycle and cell migration. Quantitative reverse transcriptase PCR (qRT-PCR) analysis confirmed that transcription of oncogenes involved in cell cycle regulation (AURKA, AURKB, CDC25B, CDK1, CCNA2, and MKI67) and the c-Met pathway (c-Met, AKT1, PTK2, CRK, PDPK1, and ARF6) was selectively repressed by THZ1. In addition, THZ1 exhibited significant anti-tumor activity in a patient-derived xenograft (PDX) model of ICC, without causing detectable side effects.","Source":"STN","category":"ANIMAL","training_data":"Therapeutic Targeting Of Cdk7 Suppresses Tumor Progression In Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is a lethal malignancy with high mortality and lack of effective therapeutic targets. Here, we found that expression of cyclin-dependent kinase 7 (CDK7) was significantly associated with higher tumor grade and worse prognosis in 96 ICC specimens. Depletion of CDK7 significantly inhibited cell growth, induced a G2/M cell cycle arrest, and reduced the migratory and invasive potential in ICC cells. Subsequent experiments demonstrated that ICC cells were highly sensitive to the CDK7 inhibitor THZ1. A low concentration of THZ1 markedly inhibited cell growth, cell cycle, migration, and invasion in ICC cell lines. RNA-sequencing (RNA-seq) analysis revealed that THZ1 treatment decreased the levels of massive oncogene transcripts, particularly those associated with cell cycle and cell migration. Quantitative reverse transcriptase PCR (qRT-PCR) analysis confirmed that transcription of oncogenes involved in cell cycle regulation (AURKA, AURKB, CDC25B, CDK1, CCNA2, and MKI67) and the c-Met pathway (c-Met, AKT1, PTK2, CRK, PDPK1, and ARF6) was selectively repressed by THZ1. In addition, THZ1 exhibited significant anti-tumor activity in a patient-derived xenograft (PDX) model of ICC, without causing detectable side effects. STN","prediction_labels":"ANIMAL"},{"cleaned":"female sex hormone receptors gallbladder cancer background higher incidence gallbladder cancer among women suggests role female sex hormones etiopathogenesis objectives paper aims study estrogen progesterone receptor er pr expression gallbladder cancer correlate receptor expression clinicopathological profile patients understand implication materials methods forty seven patients gallbladder cancer studied tumor specimens subjected histopathologic examination er pr expression evaluated using immunohistochemistry ihc receptor expression correlated clinicopathological profile patients results 47 patients 11 23 4 patients expressed sex hormone receptors receptor positive patients er pr expressed simultaneously eight patients er pr expressed individually two one patients respectively metaplasia p 0 009 dysplasia p 0 002 found significantly hormone positive group presence hormone receptor correlated early operable stage tumor p 0 048 hormone negativity correlated inoperable metastatic stage ivb p 0 004 receptor status correlation age sex menopausal status presence absence gallstones tumor type tumor differentiation desmoplasia necrosis conclusions er pr expressed mostly simultaneously significant proportion 23 4 patients gallbladder cancer receptor expression correlates metaplasia dysplasia early operable stage tumor non expression inoperable metastatic stage receptor study patients gallbladder cancer may prognostic implications pubmed","probabilities":0.9799733,"Title":"Female sex hormone receptors in gallbladder cancer","Abstract":"BACKGROUND: Higher incidence of gallbladder cancer among women suggests a role of female sex hormones in its etiopathogenesis. OBJECTIVES: This paper aims to study the estrogen/progesterone receptor (ER/PR) expression in gallbladder cancer and to correlate the receptor expression with the clinicopathological profile of patients to understand its implication. MATERIALS AND METHODS: Forty-seven patients of gallbladder cancer were studied. Tumor specimens were subjected to histopathologic examination. ER/PR expression was evaluated using immunohistochemistry (IHC). Receptor expression was correlated with the clinicopathological profile of the patients. RESULTS: Of the 47 patients, 11 (23.4 %) patients expressed sex hormone receptors. Of the receptor-positive patients, ER and PR were expressed simultaneously in eight patients while ER and PR were expressed individually in two and one patients, respectively. Metaplasia (p < 0.009) and dysplasia (p < 0.002) were found significantly more in hormone-positive group. The presence of hormone receptor correlated with early/operable stage of the tumor (p < 0.048). Hormone negativity correlated with inoperable/metastatic stage IVB (p < 0.004). The receptor status did not have any correlation with age, sex, menopausal status, presence/absence of gallstones, tumor type, tumor differentiation, desmoplasia, or necrosis. CONCLUSIONS: ER and PR are expressed, mostly simultaneously, in a significant proportion (23.4 %) of patients with gallbladder cancer. Receptor expression correlates with metaplasia, dysplasia, and early/operable stage of tumor, while its non-expression with inoperable/metastatic stage. Receptor study in patients of gallbladder cancer may have prognostic implications.","Source":"PubMed","category":"HUMAN","training_data":"Female sex hormone receptors in gallbladder cancer BACKGROUND: Higher incidence of gallbladder cancer among women suggests a role of female sex hormones in its etiopathogenesis. OBJECTIVES: This paper aims to study the estrogen/progesterone receptor (ER/PR) expression in gallbladder cancer and to correlate the receptor expression with the clinicopathological profile of patients to understand its implication. MATERIALS AND METHODS: Forty-seven patients of gallbladder cancer were studied. Tumor specimens were subjected to histopathologic examination. ER/PR expression was evaluated using immunohistochemistry (IHC). Receptor expression was correlated with the clinicopathological profile of the patients. RESULTS: Of the 47 patients, 11 (23.4 %) patients expressed sex hormone receptors. Of the receptor-positive patients, ER and PR were expressed simultaneously in eight patients while ER and PR were expressed individually in two and one patients, respectively. Metaplasia (p < 0.009) and dysplasia (p < 0.002) were found significantly more in hormone-positive group. The presence of hormone receptor correlated with early/operable stage of the tumor (p < 0.048). Hormone negativity correlated with inoperable/metastatic stage IVB (p < 0.004). The receptor status did not have any correlation with age, sex, menopausal status, presence/absence of gallstones, tumor type, tumor differentiation, desmoplasia, or necrosis. CONCLUSIONS: ER and PR are expressed, mostly simultaneously, in a significant proportion (23.4 %) of patients with gallbladder cancer. Receptor expression correlates with metaplasia, dysplasia, and early/operable stage of tumor, while its non-expression with inoperable/metastatic stage. Receptor study in patients of gallbladder cancer may have prognostic implications. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prevalence risk factors survival patients intrahepatic cholangiocarcinoma purpose investigate prevalence related risk factors survival intrahepatic cholangiocarcinoma mexican population material methods conducted cross sectional study medica sur hospital mexico city approval local research ethics committee found cases reviewing clinical records patients october 2005 january 2016 diagnosed malignant liver tumors clinical characteristics comorbidities obtained evaluate probable risk factors charlson index cases staged based tnm staging system bile duct tumors used american joint committee cancer median patient survival rates calculated using kaplan meier method results reviewed 233 cases hepatic cancer amongst hepatocellular carcinomas represented 19 3 n 45 followed intrahepatic cholangiocarcinomas accounted 7 7 n 18 median age patients intrahepatic cholangiocarcinoma 63 years presented cholestasis intrahepatic biliary ductal dilation unfortunately 89 n 16 advanced stage 80 multicentric tumors median survival 286 days among patients advanced stage tumors 25th 75th interquartile range 174 645 days correlation found presence comorbidities defined charlson index survival evaluated presence definite probable risk factors development intrahepatic cholangiocarcinoma smoking alcohol consumption primary sclerosing cholangitis discussion found overall prevalence intrahepatic cholangiocarcinoma 7 7 unfortunately patients diagnosed advanced stages smoking primary sclerosing cholangitis positive risk factors development population pubmed","probabilities":0.9799733,"Title":"Prevalence, Risk Factors, and Survival of Patients with Intrahepatic Cholangiocarcinoma","Abstract":"PURPOSE: To investigate the prevalence, related risk factors, and survival of intrahepatic cholangiocarcinoma in a Mexican population. MATERIAL AND METHODS: We conducted a cross-sectional study at Medica Sur Hospital in Mexico City with approval of the local research ethics committee. We found cases by reviewing all clinical records of in-patients between October 2005 and January 2016 who had been diagnosed with malignant liver tumors. Clinical characteristics and comorbidities were obtained to evaluate the probable risk factors and the Charlson index. The cases were staged based on the TNM staging system for bile duct tumors used by the American Joint Committee on Cancer and median patient survival rates were calculated using the Kaplan-Meier method. RESULTS: We reviewed 233 cases of hepatic cancer. Amongst these, hepatocellular carcinomas represented 19.3% (n = 45), followed by intrahepatic cholangiocarcinomas, which accounted for 7.7% (n = 18). The median age of patients with intrahepatic cholangiocarcinoma was 63 years, and most of them presented with cholestasis and intrahepatic biliary ductal dilation. Unfortunately, 89% (n = 16) of them were in an advanced stage and 80% had multicentric tumors. Median survival was 286 days among patients with advanced stage tumors (25th-75th interquartile range, 174-645 days). No correlation was found between the presence of comorbidities defined by the Charlson index, and survival. We evaluated the presence of definite and probable risk factors for the development of intrahepatic cholangiocarcinoma, that is, smoking, alcohol consumption, and primary sclerosing cholangitis. DISCUSSION: We found an overall prevalence of intrahepatic cholangiocarcinoma of 7.7%; unfortunately, these patients were diagnosed at advanced stages. Smoking and primary sclerosing cholangitis were the positive risk factors for its development in this population.","Source":"PubMed","category":"HUMAN","training_data":"Prevalence, Risk Factors, and Survival of Patients with Intrahepatic Cholangiocarcinoma PURPOSE: To investigate the prevalence, related risk factors, and survival of intrahepatic cholangiocarcinoma in a Mexican population. MATERIAL AND METHODS: We conducted a cross-sectional study at Medica Sur Hospital in Mexico City with approval of the local research ethics committee. We found cases by reviewing all clinical records of in-patients between October 2005 and January 2016 who had been diagnosed with malignant liver tumors. Clinical characteristics and comorbidities were obtained to evaluate the probable risk factors and the Charlson index. The cases were staged based on the TNM staging system for bile duct tumors used by the American Joint Committee on Cancer and median patient survival rates were calculated using the Kaplan-Meier method. RESULTS: We reviewed 233 cases of hepatic cancer. Amongst these, hepatocellular carcinomas represented 19.3% (n = 45), followed by intrahepatic cholangiocarcinomas, which accounted for 7.7% (n = 18). The median age of patients with intrahepatic cholangiocarcinoma was 63 years, and most of them presented with cholestasis and intrahepatic biliary ductal dilation. Unfortunately, 89% (n = 16) of them were in an advanced stage and 80% had multicentric tumors. Median survival was 286 days among patients with advanced stage tumors (25th-75th interquartile range, 174-645 days). No correlation was found between the presence of comorbidities defined by the Charlson index, and survival. We evaluated the presence of definite and probable risk factors for the development of intrahepatic cholangiocarcinoma, that is, smoking, alcohol consumption, and primary sclerosing cholangitis. DISCUSSION: We found an overall prevalence of intrahepatic cholangiocarcinoma of 7.7%; unfortunately, these patients were diagnosed at advanced stages. Smoking and primary sclerosing cholangitis were the positive risk factors for its development in this population. PubMed","prediction_labels":"HUMAN"},{"cleaned":"distal bile duct adenocarcinoma location influence survival abstract available google scholar","probabilities":0.9799733,"Title":"Distal Bile Duct Adenocarcinoma - Does Location Influence Survival?","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Distal Bile Duct Adenocarcinoma - Does Location Influence Survival? Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"triptolide induces apoptotic cell death human cholangiocarcinoma cells inhibition myeloid cell leukemia 1 background cholangiocarcinoma cca devastating neoplasm highly resistant current chemotherapies cca cells frequently overexpress antiapoptotic protein myeloid cell leukemia 1 mcl 1 responsible extraordinary ability evade cell death triptolide bioactive ingredient extracted chinese medicinal plant shown inhibit cell proliferation induce apoptosis several cancers methods cck 8 assay performed detect cell survival rate vitro dapi staining flow cytometry used analyze apoptosis western blot performed determine expression levels caspase 3 caspase 7 caspase 9 parp mcl 1 quantitative real time pcr immunofluorescence used detect expression levels mcl 1 nude mice xenograft model used evaluate antitumor effect triptolide vivo results triptolide reduced cell viability cholangiocarcinoma cell lines dose time dependent manner ic50 values 12 6 0 6 nm 20 5 4 2 nm 18 5 0 7 nm 48 h hucct1 qbc939 frh0201 respectively triptolide induced apoptosis cca cell lines part mitochondrial pathway using quantitative real time pcr western blot immunofluorescence shown triptolide downregulates mcl 1 mrna protein levels furthermore triptolide inhibited cca growth vivo conclusions triptolide profound antitumor effect cca probably inducing apoptosis inhibition mcl 1 triptolide promising therapeutic agent cca stn","probabilities":0.9467213,"Title":"Triptolide Induces Apoptotic Cell Death Of Human Cholangiocarcinoma Cells Through Inhibition Of Myeloid Cell Leukemia-1","Abstract":"Background: Cholangiocarcinoma (CCA), a devastating neoplasm, is highly resistant to current chemotherapies. CCA cells frequently overexpress the antiapoptotic protein myeloid cell leukemia-1(Mcl-1), which is responsible for its extraordinary ability to evade cell death. Triptolide, a bioactive ingredient extracted from Chinese medicinal plant, has been shown to inhibit cell proliferation and induce apoptosis in several cancers. \r\n\r\n Methods: CCK-8 assay was performed to detect cell survival rate in vitro. DAPI staining and Flow cytometry were used to analyze apoptosis. Western blot was performed to determine the expression levels of caspase-3, caspase-7, caspase-9, PARP, and Mcl-1. Quantitative real-time PCR and immunofluorescence were used to detect the expression levels of Mcl-1. The nude mice xenograft model was used to evaluate the antitumor effect of triptolide in vivo. \r\n\r\n Results: Triptolide reduced cell viability in cholangiocarcinoma cell lines in a dose- and time-dependent manner, with IC50 values of 12.6 ± 0.6 nM, 20.5 ± 4.2 nM, and 18.5 ± 0.7 nM at 48 h for HuCCT1, QBC939, and FRH0201 respectively. Triptolide induced apoptosis in CCA cell lines in part through mitochondrial pathway. Using quantitative real-time PCR, western blot and immunofluorescence, we have shown that triptolide downregulates Mcl-1 mRNA and protein levels. Furthermore, triptolide inhibited the CCA growth in vivo. \r\n\r\n Conclusions: Triptolide has profound antitumor effect on CCA, probably by inducing apoptosis through inhibition of Mcl-1. Triptolide would be a promising therapeutic agent for CCA.","Source":"STN","category":"ANIMAL","training_data":"Triptolide Induces Apoptotic Cell Death Of Human Cholangiocarcinoma Cells Through Inhibition Of Myeloid Cell Leukemia-1 Background: Cholangiocarcinoma (CCA), a devastating neoplasm, is highly resistant to current chemotherapies. CCA cells frequently overexpress the antiapoptotic protein myeloid cell leukemia-1(Mcl-1), which is responsible for its extraordinary ability to evade cell death. Triptolide, a bioactive ingredient extracted from Chinese medicinal plant, has been shown to inhibit cell proliferation and induce apoptosis in several cancers. \r\n\r\n Methods: CCK-8 assay was performed to detect cell survival rate in vitro. DAPI staining and Flow cytometry were used to analyze apoptosis. Western blot was performed to determine the expression levels of caspase-3, caspase-7, caspase-9, PARP, and Mcl-1. Quantitative real-time PCR and immunofluorescence were used to detect the expression levels of Mcl-1. The nude mice xenograft model was used to evaluate the antitumor effect of triptolide in vivo. \r\n\r\n Results: Triptolide reduced cell viability in cholangiocarcinoma cell lines in a dose- and time-dependent manner, with IC50 values of 12.6 ± 0.6 nM, 20.5 ± 4.2 nM, and 18.5 ± 0.7 nM at 48 h for HuCCT1, QBC939, and FRH0201 respectively. Triptolide induced apoptosis in CCA cell lines in part through mitochondrial pathway. Using quantitative real-time PCR, western blot and immunofluorescence, we have shown that triptolide downregulates Mcl-1 mRNA and protein levels. Furthermore, triptolide inhibited the CCA growth in vivo. \r\n\r\n Conclusions: Triptolide has profound antitumor effect on CCA, probably by inducing apoptosis through inhibition of Mcl-1. Triptolide would be a promising therapeutic agent for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"cholelithiasis cholecystectomy risk hepatocellular carcinoma meta analysis available evidence relationship cholelithiasis cholecystectomy risk liver cancer hence conducted meta analysis investigate relationships pubmed embase isi web knowledge searched identify published cohort studies case control studies evaluated relationships cholelithiasis cholecystectomy risk liver cancer single cohort studies evaluated incidence liver cancer among patients understood cholecystectomy february 2013 comprehensive meta analysis software used meta analysis total 11 observational studies six cohort studies five case control studies included meta analysis result meta analysis showed cholecystectomy risk ratio rr 1 59 95 confidence interval ci 1 01 2 51 i2 72 cholecystolithiasis rr 5 40 95 ci 3 69 7 89 i2 93 associated liver cancer especially intrahepatic cholangiocarcinoma icc cholecystectomy rr 3 51 95 ci 1 84 6 71 i2 26 cholecystolithiasis rr 11 06 95 ci 6 99 17 52 i2 0 pooled standardized incidence rates sir liver cancer patients understood cholecystectomy showed cholecystectomy might increase incidence liver cancer sir 1 57 95 ci 1 13 2 20 i2 15 based results meta analysis cholecystectomy cholecystolithiasis seemed involved development liver cancer especially icc however available studies case control studies short term cohort studies future studies long term cohort studies well conducted evaluate long term relationship pubmed","probabilities":0.9799733,"Title":"Cholelithiasis, cholecystectomy and risk of hepatocellular carcinoma: a meta-analysis","Abstract":"Available evidence of the relationship between cholelithiasis, cholecystectomy, and risk of liver cancer and hence we conducted a meta-analysis to investigate the relationships. PubMed, EMBASE, and ISI Web of Knowledge were searched to identify all published cohort studies and case-control studies that evaluated the relationships of cholelithiasis, cholecystectomy and risk of liver cancer and single-cohort studies which evaluated the incidence of liver cancer among patients who understood cholecystectomy (up to February 2013). Comprehensive meta-analysis software was used for meta-analysis. A total of 11 observational studies (six cohort studies and five case-control studies) were included in this meta-analysis. The result from meta-analysis showed that cholecystectomy (risk ratio [RR]: 1.59, 95% confidence interval [CI]: 1.01-2.51, I2=72%) and cholecystolithiasis (RR: 5.40, 95% CI: 3.69-7.89, I2=93%) was associated with more liver cancer, especially for intrahepatic cholangiocarcinoma (ICC) (cholecystectomy: RR: 3.51, 95% CI: 1.84-6.71, I2=26%; cholecystolithiasis: RR: 11.06, 95% CI: 6.99-17.52, I2=0%). The pooled standardized incidence rates (SIR) of liver cancer in patients who understood cholecystectomy showed cholecystectomy might increase the incidence of liver cancer (SIR: 1.57, 95% CI: 1.13-2.20, I2=15%). Based on the results of the meta-analysis, cholecystectomy and cholecystolithiasis seemed to be involved in the development of liver cancer, especially for ICC. However, most available studies were case-control studies and short-term cohort studies, so the future studies should more long-term cohort studies should be well-conducted to evaluate the long-term relationship.","Source":"PubMed","category":"HUMAN","training_data":"Cholelithiasis, cholecystectomy and risk of hepatocellular carcinoma: a meta-analysis Available evidence of the relationship between cholelithiasis, cholecystectomy, and risk of liver cancer and hence we conducted a meta-analysis to investigate the relationships. PubMed, EMBASE, and ISI Web of Knowledge were searched to identify all published cohort studies and case-control studies that evaluated the relationships of cholelithiasis, cholecystectomy and risk of liver cancer and single-cohort studies which evaluated the incidence of liver cancer among patients who understood cholecystectomy (up to February 2013). Comprehensive meta-analysis software was used for meta-analysis. A total of 11 observational studies (six cohort studies and five case-control studies) were included in this meta-analysis. The result from meta-analysis showed that cholecystectomy (risk ratio [RR]: 1.59, 95% confidence interval [CI]: 1.01-2.51, I2=72%) and cholecystolithiasis (RR: 5.40, 95% CI: 3.69-7.89, I2=93%) was associated with more liver cancer, especially for intrahepatic cholangiocarcinoma (ICC) (cholecystectomy: RR: 3.51, 95% CI: 1.84-6.71, I2=26%; cholecystolithiasis: RR: 11.06, 95% CI: 6.99-17.52, I2=0%). The pooled standardized incidence rates (SIR) of liver cancer in patients who understood cholecystectomy showed cholecystectomy might increase the incidence of liver cancer (SIR: 1.57, 95% CI: 1.13-2.20, I2=15%). Based on the results of the meta-analysis, cholecystectomy and cholecystolithiasis seemed to be involved in the development of liver cancer, especially for ICC. However, most available studies were case-control studies and short-term cohort studies, so the future studies should more long-term cohort studies should be well-conducted to evaluate the long-term relationship. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison clinicopathological features survival small bile duct type bile ductular type intrahepatic cholangiocarcinoma background classification intrahepatic cholangiocarcinomas iccs reported several studies however remains controversial materials methods january 2003 december 2015 94 patients underwent hepatectomy icc iccs 63 patients classified predominantly small bile duct type bile ductular type icc included analysis results thirty seven patients 58 7 classified small bile duct icc group 26 41 3 bile ductular icc group multivariate analysis identified intrahepatic metastasis hazard ratio hr 2 53 p 0 011 small bile duct icc hr 2 05 p 0 046 portal vein invasion hr 2 05 p 0 047 independent prognostic factors poorer survival conclusion important correctly distinguish small bile duct bile ductular icc types two types clearly different clinicopathological prognostic features stn","probabilities":0.9799733,"Title":"Comparison Of The Clinicopathological Features And Survival In Small Bile Duct Type And Bile Ductular Type Intrahepatic Cholangiocarcinoma","Abstract":"Background: The classification of intrahepatic cholangiocarcinomas (ICCs) has been reported in several studies, however, it remains controversial. \r\n\r\n Materials and methods: Between January 2003 and December 2015, 94 patients underwent hepatectomy for ICC. The ICCs of 63 of these patients were classified as predominantly small bile duct type or bile ductular type ICC and were included in this analysis. \r\n\r\n Results: Thirty-seven patients (58.7%) were classified into the small bile duct ICC group, and 26 (41.3%) into the bile ductular ICC group. A multivariate analysis identified intrahepatic metastasis [hazard ratio (HR)=2.53, p=0.011], small bile duct ICC (HR=2.05, p=0.046) and portal vein invasion (HR 2.05, p=0.047) as independent prognostic factors for poorer survival. \r\n\r\n Conclusion: It is important to correctly distinguish between small bile duct and bile ductular ICC types because these two types clearly have different clinicopathological and prognostic features.","Source":"STN","category":"HUMAN","training_data":"Comparison Of The Clinicopathological Features And Survival In Small Bile Duct Type And Bile Ductular Type Intrahepatic Cholangiocarcinoma Background: The classification of intrahepatic cholangiocarcinomas (ICCs) has been reported in several studies, however, it remains controversial. \r\n\r\n Materials and methods: Between January 2003 and December 2015, 94 patients underwent hepatectomy for ICC. The ICCs of 63 of these patients were classified as predominantly small bile duct type or bile ductular type ICC and were included in this analysis. \r\n\r\n Results: Thirty-seven patients (58.7%) were classified into the small bile duct ICC group, and 26 (41.3%) into the bile ductular ICC group. A multivariate analysis identified intrahepatic metastasis [hazard ratio (HR)=2.53, p=0.011], small bile duct ICC (HR=2.05, p=0.046) and portal vein invasion (HR 2.05, p=0.047) as independent prognostic factors for poorer survival. \r\n\r\n Conclusion: It is important to correctly distinguish between small bile duct and bile ductular ICC types because these two types clearly have different clinicopathological and prognostic features. STN","prediction_labels":"HUMAN"},{"cleaned":"hepatitis b virus infection risk cancer elderly us population hepatitis b virus hbv infection causes hepatocellular carcinoma hcc associations cancers established systematically assessed associations hbv infection cancers us elderly population conducted case control study using surveillance epidemiology end results seer medicare database us adults aged 66 years cases n 1 825 316 people first cancers diagnosed seer registries 1993 2013 controls n 200 000 randomly selected cancer free individuals frequency matched cases age sex race calendar year associations hbv infection ascertained medicare claims assessed logistic regression hbv prevalence higher cases controls 0 6 vs 0 5 hbv positively associated cancers stomach adjusted odds ratio aor 1 19 95 confidence intervals ci 1 03 1 37 anus 1 66 1 17 2 33 liver 10 6 9 66 11 6 intrahepatic bile ducts 1 67 1 18 2 37 nasopharynx 2 08 1 33 3 25 well myelodysplastic syndrome 1 26 1 07 1 49 diffuse large b cell lymphoma dlbcl 1 24 1 06 1 46 inverse associations observed female breast aor 0 86 95 ci 0 76 0 98 prostate 0 81 0 73 0 91 cancers chronic lymphocytic leukemia 0 77 0 62 0 96 associations maintained sensitivity analyses conducted people without claims cirrhosis hepatitis c human immunodeficiency virus infections hbv infection associated increased risk cancers hcc bile duct cancers dlbcl biological mechanisms hbv may lead cancers need explored pubmed","probabilities":0.962963,"Title":"Hepatitis B virus infection and the risk of cancer in the elderly US population","Abstract":"Hepatitis B virus (HBV) infection causes hepatocellular carcinoma (HCC). Associations with other cancers are not established. We systematically assessed associations between HBV infection and cancers in the US elderly population. We conducted a case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database in US adults aged ≥66 years. Cases (N = 1,825,316) were people with first cancers diagnosed in SEER registries (1993-2013). Controls (N = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race and calendar year. Associations with HBV infection (ascertained by Medicare claims) were assessed by logistic regression. HBV prevalence was higher in cases than controls (0.6% vs. 0.5%). HBV was positively associated with cancers of the stomach (adjusted odds ratio [aOR] = 1.19; 95% confidence intervals [CI] = 1.03-1.37), anus (1.66; 1.17-2.33), liver (10.6; 9.66-11.6), intrahepatic bile ducts (1.67; 1.18-2.37), nasopharynx (2.08; 1.33-3.25), as well as myelodysplastic syndrome (1.26; 1.07-1.49) and diffuse large B-cell lymphoma (DLBCL) (1.24; 1.06-1.46). Inverse associations were observed with female breast (aOR = 0.86; 95%CI = 0.76-0.98) and prostate (0.81; 0.73-0.91) cancers and chronic lymphocytic leukemia (0.77; 0.62-0.96). Associations were maintained in sensitivity analyses conducted in people without claims for cirrhosis or hepatitis C or human immunodeficiency virus infections. HBV infection is associated with increased risk of cancers other than HCC, such as bile duct cancers and DLBCL. The biological mechanisms by which HBV may lead to these cancers need to be explored.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis B virus infection and the risk of cancer in the elderly US population Hepatitis B virus (HBV) infection causes hepatocellular carcinoma (HCC). Associations with other cancers are not established. We systematically assessed associations between HBV infection and cancers in the US elderly population. We conducted a case-control study using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database in US adults aged ≥66 years. Cases (N = 1,825,316) were people with first cancers diagnosed in SEER registries (1993-2013). Controls (N = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race and calendar year. Associations with HBV infection (ascertained by Medicare claims) were assessed by logistic regression. HBV prevalence was higher in cases than controls (0.6% vs. 0.5%). HBV was positively associated with cancers of the stomach (adjusted odds ratio [aOR] = 1.19; 95% confidence intervals [CI] = 1.03-1.37), anus (1.66; 1.17-2.33), liver (10.6; 9.66-11.6), intrahepatic bile ducts (1.67; 1.18-2.37), nasopharynx (2.08; 1.33-3.25), as well as myelodysplastic syndrome (1.26; 1.07-1.49) and diffuse large B-cell lymphoma (DLBCL) (1.24; 1.06-1.46). Inverse associations were observed with female breast (aOR = 0.86; 95%CI = 0.76-0.98) and prostate (0.81; 0.73-0.91) cancers and chronic lymphocytic leukemia (0.77; 0.62-0.96). Associations were maintained in sensitivity analyses conducted in people without claims for cirrhosis or hepatitis C or human immunodeficiency virus infections. HBV infection is associated with increased risk of cancers other than HCC, such as bile duct cancers and DLBCL. The biological mechanisms by which HBV may lead to these cancers need to be explored. PubMed","prediction_labels":"HUMAN"},{"cleaned":"unresectable intrahepatic cholangiocarcinoma systemic plus hepatic arterial infusion chemotherapy associated longer survival comparison systemic chemotherapy alone background intrahepatic cholangiocarcinoma icc associated poor survival study compared outcomes patients unresectable icc treated hepatic arterial infusion hai plus systemic chemotherapy sys outcomes patients treated sys alone methods consecutive patients icc retrospectively reviewed clinicopathologic data reviewed survival rates compared kaplan meier analysis log rank testing results january 2000 august 2012 525 patients icc evaluated memorial sloan kettering cancer center 236 patients unresectable tumors locally advanced metastatic analyzed disease confined liver 104 patients underwent treatment combined hai sys n 78 75 sys alone n 26 25 response rate combined group better rate group receiving sys alone although reach statistical significance 59 vs 39 p 11 overall survival combined group longer overall survival patients received sys alone 30 8 vs 18 4 months p 001 difference maintained patients portal lymph node disease included survival analysis 29 6 months hai sys n 93 vs 15 9 months sys n 74 p 001 eight patients initially presented unresectable tumors responded enough undergo complete resection median overall survival 37 months range 10 4 92 3 months conclusions patients unresectable icc confined liver limited regional nodal disease combination sys hai chemotherapy associated greater survival sys alone cancer 2016 122 758 765 2015 american cancer society pubmed","probabilities":0.9799733,"Title":"Unresectable intrahepatic cholangiocarcinoma: Systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with poor survival. This study compared the outcomes of patients with unresectable ICC treated with hepatic arterial infusion (HAI) plus systemic chemotherapy (SYS) with the outcomes of patients treated with SYS alone. METHODS: Consecutive patients with ICC were retrospectively reviewed. Clinicopathologic data were reviewed. Survival rates were compared by Kaplan-Meier analysis and log-rank testing. RESULTS: Between January 2000 and August 2012, 525 patients with ICC were evaluated at Memorial Sloan Kettering Cancer Center, and 236 patients with unresectable tumors (locally advanced or metastatic) were analyzed. Disease was confined to the liver in 104 patients, who underwent treatment with combined HAI and SYS (n = 78 or 75%) or SYS alone (n = 26 or 25%). The response rate in the combined group was better than the rate in the group receiving SYS alone, although this did not reach statistical significance (59% vs 39%, P = .11). Overall survival for the combined group was longer than overall survival for the patients who received SYS alone (30.8 vs 18.4 months, P < .001), and this difference was maintained when patients with portal lymph node disease were included in the survival analysis (29.6 months with HAI and SYS [n = 93] vs 15.9 months with SYS [n = 74], P < .001). Eight patients who initially presented with unresectable tumors responded enough to undergo complete resection and had a median overall survival of 37 months (range, 10.4-92.3 months). CONCLUSIONS: In patients with unresectable ICC confined to the liver or with limited regional nodal disease, a combination of SYS and HAI chemotherapy is associated with greater survival than SYS alone. Cancer 2016;122:758-765. © 2015 American Cancer Society.","Source":"PubMed","category":"HUMAN","training_data":"Unresectable intrahepatic cholangiocarcinoma: Systemic plus hepatic arterial infusion chemotherapy is associated with longer survival in comparison with systemic chemotherapy alone BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with poor survival. This study compared the outcomes of patients with unresectable ICC treated with hepatic arterial infusion (HAI) plus systemic chemotherapy (SYS) with the outcomes of patients treated with SYS alone. METHODS: Consecutive patients with ICC were retrospectively reviewed. Clinicopathologic data were reviewed. Survival rates were compared by Kaplan-Meier analysis and log-rank testing. RESULTS: Between January 2000 and August 2012, 525 patients with ICC were evaluated at Memorial Sloan Kettering Cancer Center, and 236 patients with unresectable tumors (locally advanced or metastatic) were analyzed. Disease was confined to the liver in 104 patients, who underwent treatment with combined HAI and SYS (n = 78 or 75%) or SYS alone (n = 26 or 25%). The response rate in the combined group was better than the rate in the group receiving SYS alone, although this did not reach statistical significance (59% vs 39%, P = .11). Overall survival for the combined group was longer than overall survival for the patients who received SYS alone (30.8 vs 18.4 months, P < .001), and this difference was maintained when patients with portal lymph node disease were included in the survival analysis (29.6 months with HAI and SYS [n = 93] vs 15.9 months with SYS [n = 74], P < .001). Eight patients who initially presented with unresectable tumors responded enough to undergo complete resection and had a median overall survival of 37 months (range, 10.4-92.3 months). CONCLUSIONS: In patients with unresectable ICC confined to the liver or with limited regional nodal disease, a combination of SYS and HAI chemotherapy is associated with greater survival than SYS alone. Cancer 2016;122:758-765. © 2015 American Cancer Society. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical impact lymph node dissection surgery peripheral type intrahepatic cholangiocarcinoma purpose investigate prognostic factors peripheral type intrahepatic cholangiocarcinoma pp ihcc evaluate surgical outcomes according surgical strategy alterations methods twenty two patients divided two groups according surgical strategy extended surgery group ex group n 10 composed underwent hepatic lobectomy combined lymph node ln dissection bile duct resection customized surgery group cx group n 12 composed underwent hepatectomy bile duct resection according tumor spread ln dissection performed patients without ln metastasis results multivariate analysis revealed r2 resection ln metastasis intrahepatic metastasis independent prognostic factors ln dissection significantly infrequent cx group survival curative resection similar two groups 3 year survival 42 9 vs 57 1 liver metastasis frequent primary recurrence occurring 80 patients groups conclusions curative surgery might improve prognosis patients pp ihcc routine ln dissection recommended particularly patients without ln metastasis surgery alone including ln dissection control type tumor additional treatment given pubmed","probabilities":0.9799733,"Title":"Clinical impact of lymph node dissection in surgery for peripheral-type intrahepatic cholangiocarcinoma","Abstract":"PURPOSE: To investigate the prognostic factors of peripheral-type intrahepatic cholangiocarcinoma (PP-IHCC) and evaluate the surgical outcomes according to surgical strategy alterations. METHODS: Twenty-two patients were divided into two groups according to the surgical strategy: an extended surgery group (Ex group: n = 10), composed of those who underwent hepatic lobectomy combined with lymph node (LN) dissection and bile duct resection; and a customized surgery group (Cx group: n = 12), composed of those who underwent hepatectomy and bile duct resection according to tumor spread. LN dissection was not performed in patients without LN metastasis. RESULTS: Multivariate analysis revealed that R2 resection, LN metastasis, and intrahepatic metastasis were independent prognostic factors. LN dissection was significantly infrequent in the Cx group. Survival after curative resection was similar in the two groups (3-year survival: 42.9 vs. 57.1%). Liver metastasis was the most frequent primary recurrence, occurring in more than 80% of patients from both groups. CONCLUSIONS: Curative surgery might improve the prognosis of patients with PP-IHCC, but routine LN dissection is not recommended, particularly for patients without LN metastasis. Surgery alone, including LN dissection, cannot control this type of tumor, and additional treatment should be given.","Source":"PubMed","category":"HUMAN","training_data":"Clinical impact of lymph node dissection in surgery for peripheral-type intrahepatic cholangiocarcinoma PURPOSE: To investigate the prognostic factors of peripheral-type intrahepatic cholangiocarcinoma (PP-IHCC) and evaluate the surgical outcomes according to surgical strategy alterations. METHODS: Twenty-two patients were divided into two groups according to the surgical strategy: an extended surgery group (Ex group: n = 10), composed of those who underwent hepatic lobectomy combined with lymph node (LN) dissection and bile duct resection; and a customized surgery group (Cx group: n = 12), composed of those who underwent hepatectomy and bile duct resection according to tumor spread. LN dissection was not performed in patients without LN metastasis. RESULTS: Multivariate analysis revealed that R2 resection, LN metastasis, and intrahepatic metastasis were independent prognostic factors. LN dissection was significantly infrequent in the Cx group. Survival after curative resection was similar in the two groups (3-year survival: 42.9 vs. 57.1%). Liver metastasis was the most frequent primary recurrence, occurring in more than 80% of patients from both groups. CONCLUSIONS: Curative surgery might improve the prognosis of patients with PP-IHCC, but routine LN dissection is not recommended, particularly for patients without LN metastasis. Surgery alone, including LN dissection, cannot control this type of tumor, and additional treatment should be given. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ca19 9 level intrahepatic cholangiocarcinoma independently associated increased mortality hazard aggressive tumor biology ncdb study introduction triage patients elevated ca19 9 intrahepatic cholangiocarcinoma icc remains undefined hypothesized elevation ca 19 9 normal considered biologically borderline prompt multidisciplinary therapy approach methods national cancer data base 2008 2011 reviewed patients icc measured ca 19 9 non secretors analyzed separately patients stratified ca 19 9 normal reference range 37 u ml unadjusted kaplan meier analysis adjusted cox proportional hazards modeling overall survival os performed results 1734 patients measured ca 19 9 identified 148 8 5 non secretors 435 25 1 normal ca 19 9 levels 1151 66 4 elevated levels 294 patients 16 9 sufficient information staging among stage patients n 223 26 11 6 non secretors 78 34 9 normal levels 119 53 5 elevated levels demographics peri operative outcomes similar ca 19 9 groups stages stage specific survival decreased stages patients elevated ca 19 9 difference survival greatest stage see figure cox modeling adjusting patient comorbidity pathologic adjuvant treatment variables revealed elevated ca 19 9 independently confers increased mortality hazard overall hr 1 43 p 0 01 stages hr 1 85 1 48 2 10 1 24 p 0 03 stage 1 4 respectively comparison nodal status margin positivity conferred increased mortality hazards 1 38 p 0 06 1 87 p 0 01 respectively conclusions elevated ca 19 9 independent risk factor mortality similar magnitude nodal margin status may merit consideration inclusion new staging variable multi disciplinary therapeutic approach considered patients icc ca 19 9 elevation normal google scholar","probabilities":0.9799733,"Title":"Ca19-9 Level In Intrahepatic Cholangiocarcinoma Is Independently Associated With Increased Mortality Hazard And Aggressive Tumor Biology: A Ncdb Study","Abstract":"Introduction: Triage of patients with elevated CA19-9 in intrahepatic cholangiocarcinoma (ICC) remains undefined. We hypothesized that any elevation of CA 19-9 above normal should be considered biologically borderline and prompt a multidisciplinary therapy approach. Methods: The National Cancer Data Base (2008-2011) was reviewed for patients with ICC and measured CA 19-9. Non-secretors were analyzed separately. Patients were stratified by CA 19-9 above and below normal reference range (37 U/mL). Unadjusted Kaplan-Meier analysis and adjusted Cox proportional hazards modeling of overall survival (OS) were performed. Results: 1734 patients with measured CA 19-9 were identified. Of these, 148 (8.5%) were non-secretors, 435 (25.1%) had normal CA 19-9 levels, and 1151 (66.4%) had elevated levels. 294 patients (16.9%) did not have sufficient information for staging. Among Stage I patients (N=223), 26 (11.6%) were non-secretors, 78 (34.9%) had normal levels, and 119 (53.5%) had elevated levels. Demographics and peri-operative outcomes were similar between CA 19-9 groups in all stages. Stage-specific survival was decreased in all stages for patients with elevated CA 19-9, and the difference in survival was greatest in Stage I (see figure). Cox modeling adjusting for patient comorbidity, pathologic, and adjuvant treatment variables revealed elevated CA 19-9 independently confers increased mortality hazard overall (HR 1.43, p<0.01) and in all stages (HR’s 1.85, 1.48, 2.10, and 1.24, all p<0.03 in Stage 1-4 respectively). For comparison, nodal status and margin positivity conferred increased mortality hazards of 1.38 (p=0.06) and 1.87 (p<0.01) respectively. Conclusions: Elevated CA 19-9 is an independent risk factor for mortality similar in magnitude to nodal and margin status and this may merit its consideration for inclusion as a new staging variable. A multi-disciplinary therapeutic approach should be considered in patients with ICC and any CA 19-9 elevation above normal.","Source":"Google Scholar","category":"HUMAN","training_data":"Ca19-9 Level In Intrahepatic Cholangiocarcinoma Is Independently Associated With Increased Mortality Hazard And Aggressive Tumor Biology: A Ncdb Study Introduction: Triage of patients with elevated CA19-9 in intrahepatic cholangiocarcinoma (ICC) remains undefined. We hypothesized that any elevation of CA 19-9 above normal should be considered biologically borderline and prompt a multidisciplinary therapy approach. Methods: The National Cancer Data Base (2008-2011) was reviewed for patients with ICC and measured CA 19-9. Non-secretors were analyzed separately. Patients were stratified by CA 19-9 above and below normal reference range (37 U/mL). Unadjusted Kaplan-Meier analysis and adjusted Cox proportional hazards modeling of overall survival (OS) were performed. Results: 1734 patients with measured CA 19-9 were identified. Of these, 148 (8.5%) were non-secretors, 435 (25.1%) had normal CA 19-9 levels, and 1151 (66.4%) had elevated levels. 294 patients (16.9%) did not have sufficient information for staging. Among Stage I patients (N=223), 26 (11.6%) were non-secretors, 78 (34.9%) had normal levels, and 119 (53.5%) had elevated levels. Demographics and peri-operative outcomes were similar between CA 19-9 groups in all stages. Stage-specific survival was decreased in all stages for patients with elevated CA 19-9, and the difference in survival was greatest in Stage I (see figure). Cox modeling adjusting for patient comorbidity, pathologic, and adjuvant treatment variables revealed elevated CA 19-9 independently confers increased mortality hazard overall (HR 1.43, p<0.01) and in all stages (HR’s 1.85, 1.48, 2.10, and 1.24, all p<0.03 in Stage 1-4 respectively). For comparison, nodal status and margin positivity conferred increased mortality hazards of 1.38 (p=0.06) and 1.87 (p<0.01) respectively. Conclusions: Elevated CA 19-9 is an independent risk factor for mortality similar in magnitude to nodal and margin status and this may merit its consideration for inclusion as a new staging variable. A multi-disciplinary therapeutic approach should be considered in patients with ICC and any CA 19-9 elevation above normal. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"yttrium 90 transarterial radioembolization chemotherapy refractory intrahepatic cholangiocarcinoma prospective observational study purpose evaluate safety efficacy yttrium 90 transarterial radioembolization tare treatment unresectable chemotherapy refractory intrahepatic cholangiocarcinoma icc methods prospective observational study carried 10 centers 2013 2017 tare plus standard care delivered patients unresectable chemotherapy refractory chemotherapy intolerant icc primary outcome overall survival secondary outcomes included safety progression free survival pfs liver specific progression free survival lpfs results sixty one patients treated tare patients 53 male median age 64 years 91 performance status 0 1 92 received prior chemotherapy 59 extrahepatic disease median follow 13 9 months 95 confidence interval ci 9 6 18 1 overall survival 8 7 months 95 ci 5 3 12 1 37 patients survived 12 months pfs 2 8 months 95 ci 2 6 3 1 lpfs 3 1 months 95 ci 1 3 4 8 one severe complication abdominal pain occurred time tare procedure thirty patients experienced total 49 adverse events 8 grade 3 common grade 1 2 fatigue abdominal pain total 77 abnormal laboratory value events recorded 4 grade 3 conclusions patients advanced icc limited therapeutic options poor prognosis prospective study examined survival patients unresectable chemotherapy refractory primary icc treated tare real world practice results demonstrate treatment merits investigation patient cohort larger study including collection patient reported outcomes pubmed","probabilities":0.9799733,"Title":"Yttrium-90 Transarterial Radioembolization for Chemotherapy-Refractory Intrahepatic Cholangiocarcinoma: A Prospective, Observational Study","Abstract":"PURPOSE: To evaluate the safety and efficacy of yttrium-90 transarterial radioembolization (TARE) for the treatment of unresectable, chemotherapy-refractory intrahepatic cholangiocarcinoma (ICC). METHODS: A prospective, observational study was carried out in 10 centers between 2013 and 2017. TARE plus standard care was delivered to patients with unresectable, chemotherapy-refractory or chemotherapy-intolerant ICC. Primary outcome was overall survival. Secondary outcomes included safety, progression-free survival (PFS), and liver-specific progression-free survival (LPFS). RESULTS: Sixty-one patients were treated with TARE. Patients were 53% male; median age was 64 years; 91% had performance status 0/1; 92% had received prior chemotherapy; and 59% had no extrahepatic disease. Median follow-up was 13.9 months (95% confidence interval [CI], 9.6-18.1). Overall survival was 8.7 months (95% CI, 5.3-12.1), and 37% of patients survived to 12 months. PFS was 2.8 months (95% CI, 2.6-3.1), and LPFS was 3.1 months (95% CI, 1.3-4.8). One severe complication (abdominal pain) occurred at the time of the TARE procedure. Thirty patients experienced a total of 49 adverse events, of which 8% were grade ≥3; most common were grade 1-2 fatigue and abdominal pain. A total of 77 abnormal laboratory value events were recorded, of which 4% were grade ≥3. CONCLUSIONS: Patients with advanced ICC have limited therapeutic options and a poor prognosis. This prospective study examined the survival of patients with unresectable, chemotherapy-refractory primary ICC treated with TARE in real-world practice. The results demonstrate that this treatment merits further investigation in this patient cohort in a larger study, including collection of patient-reported outcomes.","Source":"PubMed","category":"HUMAN","training_data":"Yttrium-90 Transarterial Radioembolization for Chemotherapy-Refractory Intrahepatic Cholangiocarcinoma: A Prospective, Observational Study PURPOSE: To evaluate the safety and efficacy of yttrium-90 transarterial radioembolization (TARE) for the treatment of unresectable, chemotherapy-refractory intrahepatic cholangiocarcinoma (ICC). METHODS: A prospective, observational study was carried out in 10 centers between 2013 and 2017. TARE plus standard care was delivered to patients with unresectable, chemotherapy-refractory or chemotherapy-intolerant ICC. Primary outcome was overall survival. Secondary outcomes included safety, progression-free survival (PFS), and liver-specific progression-free survival (LPFS). RESULTS: Sixty-one patients were treated with TARE. Patients were 53% male; median age was 64 years; 91% had performance status 0/1; 92% had received prior chemotherapy; and 59% had no extrahepatic disease. Median follow-up was 13.9 months (95% confidence interval [CI], 9.6-18.1). Overall survival was 8.7 months (95% CI, 5.3-12.1), and 37% of patients survived to 12 months. PFS was 2.8 months (95% CI, 2.6-3.1), and LPFS was 3.1 months (95% CI, 1.3-4.8). One severe complication (abdominal pain) occurred at the time of the TARE procedure. Thirty patients experienced a total of 49 adverse events, of which 8% were grade ≥3; most common were grade 1-2 fatigue and abdominal pain. A total of 77 abnormal laboratory value events were recorded, of which 4% were grade ≥3. CONCLUSIONS: Patients with advanced ICC have limited therapeutic options and a poor prognosis. This prospective study examined the survival of patients with unresectable, chemotherapy-refractory primary ICC treated with TARE in real-world practice. The results demonstrate that this treatment merits further investigation in this patient cohort in a larger study, including collection of patient-reported outcomes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"demographics tumor characteristics treatment survival patients klatskin tumors background objective study investigate incidence demographics tumor characteristics treatment survival patients hilar cholangiocarcinoma methods data klatskin tumors 2004 2013 extracted surveillance epidemiology end results registry epidemiology tumors analyzed results total 254 patients klatskin tumors identified overall age adjusted incidence klatskin tumors 2004 2013 0 38 per 1 000 000 per year gradual decline incidence noted highest 0 44 2005 lowest 0 24 2010 males higher incidence klatskin tumors compared females 0 47 vs 0 25 per 1 000 000 per year tumors common among asian pacific islanders age adjusted incidence rate 0 48 per 1 000 000 incidence increased age peak incidence ages 80 84 years majority tumors extrahepatic 67 3 approximately one fourth 22 4 patients metastatic disease presentation 26 8 patients surgically resectable disease presentation one 5 year cause specific survival klatskin tumors 41 10 4 respectively median survival 7 months cox proportional hazard regression analysis extrahepatic tumors hazard ratio hr 0 54 95 confidence interval ci 0 37 0 80 p 0 02 treated surgically hr 0 47 95 ci 0 29 0 77 p 0 003 significantly better outcomes conclusions klatskin tumors rare poor prognosis low survival rate among tumors extrahepatic surgically treated tumors tend better outcomes google scholar","probabilities":0.9799733,"Title":"Demographics Tumor Characteristics Treatment And Survival Of Patients With Klatskin Tumors","Abstract":"Background\nThe objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with hilar cholangiocarcinoma.\nMethods\nData on Klatskin tumors between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results Registry. The epidemiology of these tumors was then analyzed.\nResults\nA total of 254 patients with Klatskin tumors were identified. The overall age-adjusted incidence of Klatskin tumors between 2004 and 2013 was 0.38 per 1,000,000 per year. A gradual decline in the incidence was noted, with the highest (0.44) in 2005 and lowest (0.24) in 2010. Males had a higher incidence of Klatskin tumors compared to females (0.47 vs. 0.25 per 1,000,000 per year). These tumors were more common among Asian and Pacific islanders, who had an age-adjusted incidence rate of 0.48 per 1,000,000. Incidence increased with age, with the peak incidence between the ages of 80 and 84 years. The majority of the tumors were extrahepatic (67.3%). Approximately one-fourth (22.4%) of these patients had metastatic disease at presentation. Only 26.8% of patients had surgically resectable disease at presentation. One- and 5-year cause-specific survival for Klatskin tumors was 41% and 10.4%, respectively, with a median survival of 7 months. On Cox proportional hazard regression analysis, extrahepatic tumors (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.37-0.80, P=0.02) and those treated surgically (HR 0.47, 95%CI 0.29-0.77, P=0.003) had significantly better outcomes.\nConclusions\nKlatskin tumors are rare and have a very poor prognosis with low survival rate. Among these tumors, extrahepatic and surgically treated tumors tend to have better outcomes.","Source":"Google Scholar","category":"HUMAN","training_data":"Demographics Tumor Characteristics Treatment And Survival Of Patients With Klatskin Tumors Background\nThe objective of this study was to investigate the incidence, demographics, tumor characteristics, treatment, and survival of patients with hilar cholangiocarcinoma.\nMethods\nData on Klatskin tumors between 2004 and 2013 was extracted from the Surveillance, Epidemiology and End Results Registry. The epidemiology of these tumors was then analyzed.\nResults\nA total of 254 patients with Klatskin tumors were identified. The overall age-adjusted incidence of Klatskin tumors between 2004 and 2013 was 0.38 per 1,000,000 per year. A gradual decline in the incidence was noted, with the highest (0.44) in 2005 and lowest (0.24) in 2010. Males had a higher incidence of Klatskin tumors compared to females (0.47 vs. 0.25 per 1,000,000 per year). These tumors were more common among Asian and Pacific islanders, who had an age-adjusted incidence rate of 0.48 per 1,000,000. Incidence increased with age, with the peak incidence between the ages of 80 and 84 years. The majority of the tumors were extrahepatic (67.3%). Approximately one-fourth (22.4%) of these patients had metastatic disease at presentation. Only 26.8% of patients had surgically resectable disease at presentation. One- and 5-year cause-specific survival for Klatskin tumors was 41% and 10.4%, respectively, with a median survival of 7 months. On Cox proportional hazard regression analysis, extrahepatic tumors (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.37-0.80, P=0.02) and those treated surgically (HR 0.47, 95%CI 0.29-0.77, P=0.003) had significantly better outcomes.\nConclusions\nKlatskin tumors are rare and have a very poor prognosis with low survival rate. Among these tumors, extrahepatic and surgically treated tumors tend to have better outcomes. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"pathologic prognostic implications incidental versus nonincidental gallbladder cancer 10 institution study united states extrahepatic biliary malignancy consortium gallbladder cancers gbcs discovered incidentally routine cholecystectomy influence timing diagnosis disease stage treatment prognosis known patients gbc underwent resection 10 institutions 2000 2015 included patients diagnosed incidentally igbc nonincidentally non igbc compared primary outcome overall survival os 445 patients gbc 266 60 igbc 179 40 non igbc compared igbc non igbc patients likely r2 resections 43 vs 19 p 0 001 advanced stage t3 t4 70 vs 40 p 0 001 high grade tumors 50 vs 31 p 0 001 lymphovascular invasion 64 vs 45 p 0 01 positive lymph nodes 60 vs 43 p 0 009 receipt adjuvant chemotherapy similar groups 49 vs 49 non igbc associated worse median os compared igbc 17 vs 32 months p 0 001 persisted among stage iii patients 12 vs 29 months p 0 001 stages ii iv despite accounting adverse pathologic factors grade stage lymphovascular invasion margin lymph node adjuvant chemotherapy associated improved os stage iii igbc non igbc compared incidental discovery non igbc associated reduced os evident stage iii disease despite well matched adverse pathologic factors adjuvant chemotherapy associated improved survival stage iii patients incidentally discovered cancer underscores importance timing diagnosis gbc suggests two groups may represent distinct biology disease treatment paradigm may appropriate stn","probabilities":0.9799733,"Title":"Pathologic And Prognostic Implications Of Incidental Versus Nonincidental Gallbladder Cancer: A 10-Institution Study From The United States Extrahepatic Biliary Malignancy Consortium","Abstract":"Most gallbladder cancers (GBCs) are discovered incidentally after routine cholecystectomy. The influence of timing of diagnosis on disease stage, treatment, and prognosis is not known. Patients with GBC who underwent resection at 10 institutions from 2000 to 2015 were included. Patients diagnosed incidentally (IGBC) and nonincidentally (non-IGBC) were compared. Primary outcome was overall survival (OS). Of 445 patients with GBC, 266 (60%) were IGBC and 179 (40%) were non-IGBC. Compared with IGBC, non-IGBC patients were more likely to have R2 resections (43% vs 19%; P < 0.001), advanced T-stage (T3/T4: 70% vs 40%; P < 0.001), high-grade tumors (50% vs 31%; P < 0.001), lymphovascular invasion (64% vs 45%; P = 0.01), and positive lymph nodes (60% vs 43%; P = 0.009). Receipt of adjuvant chemotherapy was similar between groups (49% vs 49%). Non-IGBC was associated with worse median OS compared with IGBC (17 vs 32 months; P < 0.001), which persisted among stage III patients (12 vs 29 months; P < 0.001), but not stages I, II, or IV. Despite accounting for other adverse pathologic factors (grade, T-stage, lymphovascular invasion, margin, lymph node), adjuvant chemotherapy was associated with improved OS only in stage III IGBC, but not in non-IGBC. Compared with incidental discovery, non-IGBC is associated with reduced OS, which is most evident in stage III disease. Despite being well matched for other adverse pathologic factors, adjuvant chemotherapy was associated with improved survival only in stage III patients with incidentally discovered cancer. This underscores the importance of timing of diagnosis in GBC and suggests that these two groups may represent a distinct biology of disease, and the same treatment paradigm may not be appropriate.","Source":"STN","category":"HUMAN","training_data":"Pathologic And Prognostic Implications Of Incidental Versus Nonincidental Gallbladder Cancer: A 10-Institution Study From The United States Extrahepatic Biliary Malignancy Consortium Most gallbladder cancers (GBCs) are discovered incidentally after routine cholecystectomy. The influence of timing of diagnosis on disease stage, treatment, and prognosis is not known. Patients with GBC who underwent resection at 10 institutions from 2000 to 2015 were included. Patients diagnosed incidentally (IGBC) and nonincidentally (non-IGBC) were compared. Primary outcome was overall survival (OS). Of 445 patients with GBC, 266 (60%) were IGBC and 179 (40%) were non-IGBC. Compared with IGBC, non-IGBC patients were more likely to have R2 resections (43% vs 19%; P < 0.001), advanced T-stage (T3/T4: 70% vs 40%; P < 0.001), high-grade tumors (50% vs 31%; P < 0.001), lymphovascular invasion (64% vs 45%; P = 0.01), and positive lymph nodes (60% vs 43%; P = 0.009). Receipt of adjuvant chemotherapy was similar between groups (49% vs 49%). Non-IGBC was associated with worse median OS compared with IGBC (17 vs 32 months; P < 0.001), which persisted among stage III patients (12 vs 29 months; P < 0.001), but not stages I, II, or IV. Despite accounting for other adverse pathologic factors (grade, T-stage, lymphovascular invasion, margin, lymph node), adjuvant chemotherapy was associated with improved OS only in stage III IGBC, but not in non-IGBC. Compared with incidental discovery, non-IGBC is associated with reduced OS, which is most evident in stage III disease. Despite being well matched for other adverse pathologic factors, adjuvant chemotherapy was associated with improved survival only in stage III patients with incidentally discovered cancer. This underscores the importance of timing of diagnosis in GBC and suggests that these two groups may represent a distinct biology of disease, and the same treatment paradigm may not be appropriate. STN","prediction_labels":"HUMAN"},{"cleaned":"improved post transplant survival united states patients cholangiocarcinoma 2000 background incidence cholangiocarcinoma cca continues rise orthotopic liver transplantation olt used selected patients localized unresectable hilar cca although initial post olt survival rates poor outcomes introduction mayo clinic protocol promising increased interest olt cca nationally aims aim study determine post transplant survival prognostic factors patients undergoing olt cca methods retrospective analysis patients cca listed nationwide olt october 1987 may 2008 performed using scientific registry transplant recipients database survival curves generated using kaplan meier method compared using log rank test results 595 patients cca listed olt 359 60 3 underwent olt median age olt 49 years 66 male 91 caucasian median follow time 2 years increasing number liver transplants performed cca since 2000 1 5 year probability survival 85 8 51 4 respectively multivariate analysis significant prognostic factors decreased post olt survival included transplant 2000 hr 11 25 95 ci 1 28 98 7 acute cellular rejection hr 5 64 95 ci 1 14 27 8 conclusions survival transplant cca improved time olt used frequently treatment cca significant predictors post olt survival include history acute rejection date transplant relation publication mayo protocol results pubmed","probabilities":0.9799733,"Title":"Improved post-transplant survival in the United States for patients with cholangiocarcinoma after 2000","Abstract":"BACKGROUND: The incidence of cholangiocarcinoma (CCA) continues to rise. Orthotopic liver transplantation (OLT) can be used for selected patients with localized but unresectable hilar CCA. Although initial post-OLT survival rates were poor, outcomes after introduction of the Mayo Clinic protocol have been more promising and there has been increased interest in OLT for CCA nationally. AIMS: The aim of this study is to determine post-transplant survival and prognostic factors for patients undergoing OLT for CCA. METHODS: A retrospective analysis of all patients with CCA listed nationwide for OLT between October 1987 and May 2008 was performed using the Scientific Registry of Transplant Recipients database. Survival curves were generated using the Kaplan-Meier method and compared using log-rank test. RESULTS: Of 595 patients with CCA listed for OLT, 359 (60.3 %) underwent OLT. Median age at OLT was 49 years, 66 % were male and 91 % were Caucasian. The median follow-up time was 2 years. There has been an increasing number of liver transplants performed for CCA since 2000. The 1- and 5-year probability of survival was 85.8 and 51.4 %, respectively. On multivariate analysis, significant prognostic factors for decreased post-OLT survival included transplant before 2000 (HR 11.25, 95 % CI 1.28-98.7) and acute cellular rejection (HR 5.64, 95 % CI 1.14-27.8). CONCLUSIONS: Survival after transplant for CCA has improved over time, and OLT is being used more frequently in the treatment of CCA. Significant predictors of post-OLT survival include a history of acute rejection and date of transplant in relation to the publication of Mayo protocol results.","Source":"PubMed","category":"HUMAN","training_data":"Improved post-transplant survival in the United States for patients with cholangiocarcinoma after 2000 BACKGROUND: The incidence of cholangiocarcinoma (CCA) continues to rise. Orthotopic liver transplantation (OLT) can be used for selected patients with localized but unresectable hilar CCA. Although initial post-OLT survival rates were poor, outcomes after introduction of the Mayo Clinic protocol have been more promising and there has been increased interest in OLT for CCA nationally. AIMS: The aim of this study is to determine post-transplant survival and prognostic factors for patients undergoing OLT for CCA. METHODS: A retrospective analysis of all patients with CCA listed nationwide for OLT between October 1987 and May 2008 was performed using the Scientific Registry of Transplant Recipients database. Survival curves were generated using the Kaplan-Meier method and compared using log-rank test. RESULTS: Of 595 patients with CCA listed for OLT, 359 (60.3 %) underwent OLT. Median age at OLT was 49 years, 66 % were male and 91 % were Caucasian. The median follow-up time was 2 years. There has been an increasing number of liver transplants performed for CCA since 2000. The 1- and 5-year probability of survival was 85.8 and 51.4 %, respectively. On multivariate analysis, significant prognostic factors for decreased post-OLT survival included transplant before 2000 (HR 11.25, 95 % CI 1.28-98.7) and acute cellular rejection (HR 5.64, 95 % CI 1.14-27.8). CONCLUSIONS: Survival after transplant for CCA has improved over time, and OLT is being used more frequently in the treatment of CCA. Significant predictors of post-OLT survival include a history of acute rejection and date of transplant in relation to the publication of Mayo protocol results. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment induced changes circulating lymphocyte populations associate survival patients hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc treated hypofractionated proton therapy hpt non editable google scholar","probabilities":0.9799733,"Title":"Treatment-Induced Changes In Circulating Lymphocyte Populations Associate With Survival Of Patients With Hepatocellular Carcinoma (Hcc) And Intrahepatic Cholangiocarcinoma (Icc) Treated With Hypofractionated Proton Therapy (Hpt)","Abstract":"Non-editable","Source":"Google Scholar","category":"HUMAN","training_data":"Treatment-Induced Changes In Circulating Lymphocyte Populations Associate With Survival Of Patients With Hepatocellular Carcinoma (Hcc) And Intrahepatic Cholangiocarcinoma (Icc) Treated With Hypofractionated Proton Therapy (Hpt) Non-editable Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"late complications endoscopic sphincterotomy abstract introduction endoscopic retrograde cholangiopancreatography endoscopic sphincterotomy es changed treatment choledocholithiasis increasing number young patients requiring es raises concern regarding potential long term complications arising irreversibly altering anatomy sphincter oddi particular concern raised regarding risk late cholangiocarcioma review performed evaluating relationship es benign disease subsequent development late complications including biliary tract malignancy formation primary duct stones recurring cholangitis systematic review articles published 1970 2013 undertaken current evidence shows es safe e ective treatment common bile duct stones long term risk subsequent cholangiocarcinoma convincingly proven although many studies follow period inadequate appear associated increased incidence cholangiocarcinomas following sphincterotomy although proven causative increased risk cholangiocarcinoma following es likely small western populations however longer follow studies published may prudent avoid es young google scholar","probabilities":0.9799733,"Title":"Late Complications After Endoscopic Sphincterotomy","Abstract":"Abstract: The introduction of endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy (ES) has changed the treatment of choledocholithiasis. An increasing number of young patients are requiring ES, and this raises concern regarding any potential long-term complications arising from irreversibly altering the anatomy of the sphincter of Oddi. In particular, concern has been raised regarding the risk of late cholangiocarcioma. A review was performed evaluating the relationship between ES for benign disease and the subsequent development of late complications, including biliary tract malignancy, the formation of primary duct stones, and recurring cholangitis. A systematic review of articles published between 1970 and 2013 was undertaken. Current evidence shows that ES is a safe and effective treatment for common bile duct stones. The long-term risk of subsequent cholangiocarcinoma has not been convincingly proven although in many of these studies the follow-up period was inadequate. There does appear to be an associated increased incidence of cholangiocarcinomas following sphincterotomy although this is not proven to be causative. If there is an increased risk of cholangiocarcinoma following ES, it is likely to be small in western populations. However, until longer follow-up studies are published, it may be prudent to avoid ES in the very young.","Source":"Google Scholar","category":"HUMAN","training_data":"Late Complications After Endoscopic Sphincterotomy Abstract: The introduction of endoscopic retrograde cholangiopancreatography with endoscopic sphincterotomy (ES) has changed the treatment of choledocholithiasis. An increasing number of young patients are requiring ES, and this raises concern regarding any potential long-term complications arising from irreversibly altering the anatomy of the sphincter of Oddi. In particular, concern has been raised regarding the risk of late cholangiocarcioma. A review was performed evaluating the relationship between ES for benign disease and the subsequent development of late complications, including biliary tract malignancy, the formation of primary duct stones, and recurring cholangitis. A systematic review of articles published between 1970 and 2013 was undertaken. Current evidence shows that ES is a safe and effective treatment for common bile duct stones. The long-term risk of subsequent cholangiocarcinoma has not been convincingly proven although in many of these studies the follow-up period was inadequate. There does appear to be an associated increased incidence of cholangiocarcinomas following sphincterotomy although this is not proven to be causative. If there is an increased risk of cholangiocarcinoma following ES, it is likely to be small in western populations. However, until longer follow-up studies are published, it may be prudent to avoid ES in the very young. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"systemic therapy gallbladder cancer review first line maintenance neoadjuvant second line therapy specific gallbladder cancer gallbladder cancer common malignant cancer biliary tract distinct forms biliary tract cancer several risk factors molecular aberrations locally advanced unresectable metastatic gallbladder cancer associated poor prognosis systemic chemotherapy main form treatment available patients review focused available evidence supporting use first line chemotherapy specifically gallbladder cancer numerous non randomised studies published certain forms monotherapy combination therapy lead response rates rrs approximately 40 may prove affect overall survival notably recent phase ii study triplet therapy gemcitabine cisplatin nab paclitaxel however relatively randomised phases ii iii studies base recommendations demonstrate significant survival advantages gemcitabine containing combination therapies best supportive care chemotherapeutic monotherapy abc 02 trial established combination gemcitabine cisplatin standard therapy 2010 recent phase iii studies reported conference papers may support alternative gemcitabine containing doublet chemotherapy regimens gemcitabine combination oxaliplatin s1 manuscript also highlights available data studies examining maintenance chemotherapy biomarkers neoadjuvant therapy second line studies gallbladder cancer unfortunately insufficient evidence make recommendations regards prognosis unresectable metastatic gallbladder cancer remains poor biomarkers stratifying patients particular first line therapies defined might improved gallbladder cancer specific analysis reporting making histological primary specific data available publicly analysis pubmed","probabilities":0.9799733,"Title":"Systemic therapy of gallbladder cancer: review of first line, maintenance, neoadjuvant and second line therapy specific to gallbladder cancer","Abstract":"Gallbladder cancer is the most common malignant cancer of the biliary tract and is distinct from other forms of biliary tract cancer in several of its risk factors and molecular aberrations. Locally advanced, unresectable and metastatic gallbladder cancer is associated with a poor prognosis and systemic chemotherapy is the main form of treatment available to these patients. This review is focused on the available evidence supporting the use of first-line chemotherapy specifically for gallbladder cancer. Numerous non-randomised studies have been published and certain forms of monotherapy and combination therapy can both lead to response rates (RRs) of approximately 40% and may prove to affect overall survival, most notably a recent phase II study of triplet therapy with gemcitabine, cisplatin and nab-paclitaxel. There are however relatively few randomised phases II and III studies on which to base recommendations, but they do demonstrate significant survival advantages of gemcitabine-containing combination therapies over best supportive care and chemotherapeutic monotherapy. The ABC-02 trial established the combination of gemcitabine and cisplatin as standard therapy in 2010, but more recent phase III studies reported as conference papers may support alternative, gemcitabine-containing doublet chemotherapy regimens such as gemcitabine in combination with oxaliplatin or S1. This manuscript also highlights the available data from studies examining maintenance chemotherapy, biomarkers, neoadjuvant therapy and second line studies in gallbladder cancer; unfortunately, there is insufficient evidence to make recommendations in these regards. The prognosis for unresectable and metastatic gallbladder cancer remains poor, and biomarkers for stratifying patients to particular first line therapies are not defined. This might be improved by gallbladder cancer specific analysis and reporting, and making histological primary specific data available publicly for further analysis.","Source":"PubMed","category":"HUMAN","training_data":"Systemic therapy of gallbladder cancer: review of first line, maintenance, neoadjuvant and second line therapy specific to gallbladder cancer Gallbladder cancer is the most common malignant cancer of the biliary tract and is distinct from other forms of biliary tract cancer in several of its risk factors and molecular aberrations. Locally advanced, unresectable and metastatic gallbladder cancer is associated with a poor prognosis and systemic chemotherapy is the main form of treatment available to these patients. This review is focused on the available evidence supporting the use of first-line chemotherapy specifically for gallbladder cancer. Numerous non-randomised studies have been published and certain forms of monotherapy and combination therapy can both lead to response rates (RRs) of approximately 40% and may prove to affect overall survival, most notably a recent phase II study of triplet therapy with gemcitabine, cisplatin and nab-paclitaxel. There are however relatively few randomised phases II and III studies on which to base recommendations, but they do demonstrate significant survival advantages of gemcitabine-containing combination therapies over best supportive care and chemotherapeutic monotherapy. The ABC-02 trial established the combination of gemcitabine and cisplatin as standard therapy in 2010, but more recent phase III studies reported as conference papers may support alternative, gemcitabine-containing doublet chemotherapy regimens such as gemcitabine in combination with oxaliplatin or S1. This manuscript also highlights the available data from studies examining maintenance chemotherapy, biomarkers, neoadjuvant therapy and second line studies in gallbladder cancer; unfortunately, there is insufficient evidence to make recommendations in these regards. The prognosis for unresectable and metastatic gallbladder cancer remains poor, and biomarkers for stratifying patients to particular first line therapies are not defined. This might be improved by gallbladder cancer specific analysis and reporting, and making histological primary specific data available publicly for further analysis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"inverse prognostic relationships 18f fdg pet ct metabolic parameters patients distal bile duct cancer undergoing curative surgery purpose previous studies small number subjects purpose evaluate prognostic significance 18f fdg pet ct patients distal bile duct cancer undergoing curative surgery methods study included 40 patients m f 24 16 age 68 0 8 0 years underwent preoperative 18f fdg pet ct followed curative surgical resection participant age sex eastern cooperative oncology group performance status score baseline serum ca 19 9 level stage pathologic n stages tumor size tumor grade tumor growth pattern r0 resection adjuvant therapy included clinicopathological variables predicting overall survival pet variables maximum standardized uptake value suvmax average suv suvavg metabolic tumor volume mtv total lesion glycolysis tlg tumor kaplan meyer method cox proportional hazards model used survival analysis results total 15 40 patients 37 5 died follow period univariate analysis low suvmax 2 7 p 0 0005 low suvavg 2 6 p 0 0034 significant predictors poor overall survival multivariate analyses low suvmax hr 6 7016 95 ci 1 9961 22 4993 p 0 0047 independent prognostic factor associated poor overall survival conclusion suvmax primary tumor measured 18f fdg pet ct independent significant prognostic factor overall survival patients distal bile duct cancer however different results previous study warrant large sample sized study stn","probabilities":0.9799733,"Title":"Inverse Prognostic Relationships Of 18F-Fdg Pet/Ct Metabolic Parameters In Patients With Distal Bile Duct Cancer Undergoing Curative Surgery","Abstract":"Purpose: As there were few previous studies with a small number of subjects, the purpose of this was to evaluate the prognostic significance of 18F-FDG PET/CT in patients with distal bile duct cancer undergoing curative surgery. \r\n\r\n Methods: The study included 40 patients (M/F = 24:16; age 68.0 ± 8.0 years) who underwent preoperative 18F-FDG PET/CT followed by curative surgical resection. The participant's age, sex, Eastern Cooperative Oncology Group performance-status score, baseline serum CA 19-9 level, stage, pathologic T and N stages, tumor size, tumor grade, tumor growth pattern, R0 resection, and adjuvant therapy were included as clinicopathological variables for predicting overall survival. The PET variables were maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the tumor. The Kaplan-Meyer method and Cox proportional hazards model were used for the survival analysis. \r\n\r\n Results: A total of 15 of 40 patients (37.5%) died during the follow-up period. In univariate analysis, low SUVmax (≤ 2.7, p = 0.0005) and low SUVavg (≤ 2.6, p = 0.0034) were significant predictors of poor overall survival. In multivariate analyses, only low SUVmax (HR = 6.7016, 95% CI 1.9961-22.4993, p = 0.0047) was an independent prognostic factor associated with poor overall survival. \r\n\r\n Conclusion: The SUVmax of the primary tumor measured by 18F-FDG PET/CT was an independent significant prognostic factor for overall survival in patients with distal bile duct cancer. However, different results from a previous study warrant further large sample-sized study.","Source":"STN","category":"HUMAN","training_data":"Inverse Prognostic Relationships Of 18F-Fdg Pet/Ct Metabolic Parameters In Patients With Distal Bile Duct Cancer Undergoing Curative Surgery Purpose: As there were few previous studies with a small number of subjects, the purpose of this was to evaluate the prognostic significance of 18F-FDG PET/CT in patients with distal bile duct cancer undergoing curative surgery. \r\n\r\n Methods: The study included 40 patients (M/F = 24:16; age 68.0 ± 8.0 years) who underwent preoperative 18F-FDG PET/CT followed by curative surgical resection. The participant's age, sex, Eastern Cooperative Oncology Group performance-status score, baseline serum CA 19-9 level, stage, pathologic T and N stages, tumor size, tumor grade, tumor growth pattern, R0 resection, and adjuvant therapy were included as clinicopathological variables for predicting overall survival. The PET variables were maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the tumor. The Kaplan-Meyer method and Cox proportional hazards model were used for the survival analysis. \r\n\r\n Results: A total of 15 of 40 patients (37.5%) died during the follow-up period. In univariate analysis, low SUVmax (≤ 2.7, p = 0.0005) and low SUVavg (≤ 2.6, p = 0.0034) were significant predictors of poor overall survival. In multivariate analyses, only low SUVmax (HR = 6.7016, 95% CI 1.9961-22.4993, p = 0.0047) was an independent prognostic factor associated with poor overall survival. \r\n\r\n Conclusion: The SUVmax of the primary tumor measured by 18F-FDG PET/CT was an independent significant prognostic factor for overall survival in patients with distal bile duct cancer. However, different results from a previous study warrant further large sample-sized study. STN","prediction_labels":"HUMAN"},{"cleaned":"impact preoperative quantity quality skeletal muscle outcomes resection extrahepatic biliary malignancies background skeletal muscle depletion referred sarcopenia predicts mortality major surgery study investigated impact preoperative skeletal muscle quantity quality outcomes patients undergoing resection extrahepatic biliary cancer methods performed retrospective analysis 207 patients undergoing resection biliary cancer 2004 2013 quantity quality skeletal muscle indicated psoas muscle mass index pmi intramuscular adipose tissue content imac measured preoperative images computed tomography overall survival os recurrence free survival rfs rates compared pmi imac prognostic factors operation assessed results os rfs rates less patients low pmi low muscle quantity normal pmi p 001 p 001 5 year os 15 7 vs 53 5 os rfs rates also less patients high imac low muscle quality normal imac p 001 p 001 5 year os 23 8 vs 55 9 low pmi high imac independent factors predictive poor os hazard ratio hr 2 921 95 ci 1 920 4 470 p 001 hr 1 725 95 ci 1 159 2 590 p 007 rfs hr 2 141 95 ci 1 464 3 129 p 001 hr 1 492 95 ci 1 032 2 166 p 034 conclusion preoperative sarcopenia indicating low quantity quality skeletal muscle related closely mortality resection biliary cancer pubmed","probabilities":0.7966102,"Title":"Impact of the preoperative quantity and quality of skeletal muscle on outcomes after resection of extrahepatic biliary malignancies","Abstract":"BACKGROUND: Skeletal muscle depletion, referred to as sarcopenia, predicts mortality after major surgery. This study investigated the impact of preoperative skeletal muscle quantity and quality on outcomes in patients undergoing resection of extrahepatic biliary cancer. METHODS: We performed a retrospective analysis of 207 patients undergoing resection for biliary cancer between 2004 and 2013. The quantity and quality of skeletal muscle, indicated by the psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), were measured on preoperative images of computed tomography. Overall survival (OS) and recurrence-free survival (RFS) rates were compared by PMI and IMAC, and prognostic factors after operation were assessed. RESULTS: The OS and RFS rates were less in patients with low PMI (low muscle quantity) than in those with normal PMI (P < .001 and P < .001; 5-year OS, 15.7 vs 53.5%). The OS and RFS rates were also less in patients with high IMAC (low muscle quality) than in those with normal IMAC (P < .001 and P < .001; 5-year OS, 23.8 vs 55.9%). Low PMI and high IMAC were independent factors predictive of poor OS (hazard ratio [HR], 2.921 [95% CI, 1.920-4.470; P < .001] and HR, 1.725 [95% CI, 1.159-2.590; P = .007]) and RFS (HR, 2.141 [95% CI, 1.464-3.129, P < .001] and HR, 1.492 [95% CI, 1.032-2.166, P = .034]). CONCLUSION: Preoperative sarcopenia, indicating a low quantity and quality of skeletal muscle, is related closely to mortality after resection of biliary cancer.","Source":"PubMed","category":"HUMAN","training_data":"Impact of the preoperative quantity and quality of skeletal muscle on outcomes after resection of extrahepatic biliary malignancies BACKGROUND: Skeletal muscle depletion, referred to as sarcopenia, predicts mortality after major surgery. This study investigated the impact of preoperative skeletal muscle quantity and quality on outcomes in patients undergoing resection of extrahepatic biliary cancer. METHODS: We performed a retrospective analysis of 207 patients undergoing resection for biliary cancer between 2004 and 2013. The quantity and quality of skeletal muscle, indicated by the psoas muscle mass index (PMI) and intramuscular adipose tissue content (IMAC), were measured on preoperative images of computed tomography. Overall survival (OS) and recurrence-free survival (RFS) rates were compared by PMI and IMAC, and prognostic factors after operation were assessed. RESULTS: The OS and RFS rates were less in patients with low PMI (low muscle quantity) than in those with normal PMI (P < .001 and P < .001; 5-year OS, 15.7 vs 53.5%). The OS and RFS rates were also less in patients with high IMAC (low muscle quality) than in those with normal IMAC (P < .001 and P < .001; 5-year OS, 23.8 vs 55.9%). Low PMI and high IMAC were independent factors predictive of poor OS (hazard ratio [HR], 2.921 [95% CI, 1.920-4.470; P < .001] and HR, 1.725 [95% CI, 1.159-2.590; P = .007]) and RFS (HR, 2.141 [95% CI, 1.464-3.129, P < .001] and HR, 1.492 [95% CI, 1.032-2.166, P = .034]). CONCLUSION: Preoperative sarcopenia, indicating a low quantity and quality of skeletal muscle, is related closely to mortality after resection of biliary cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"port site resection necessary surgical management gallbladder cancer introduction gallbladder carcinoma frequently discovered incidentally pathologic examination specimen laparoscopic cholecystectomy lc performed presumed benign disease objective present study assess role excision port sites initial lc patients incidental gallbladder carcinoma igbc french registry methods data patients igbc identified lc 1998 2008 retrospectively collated french multicenter database among patients undergoing re operation curative intent patients port site excision pse compared patients without pse analyzed differences recurrence patterns survival results among 218 patients igbc lc 68 men 150 women median age 64 years 148 underwent re resection curative intent 54 patients pse 94 groups comparable regard demographic data gender age 70 co morbidities surgical procedures major resection lymphadenectomy main bile duct resection postoperative morbidity pse group depth tumor invasion t1b six t2 24 t3 22 t4 two significantly different patients without pse p 0 69 port site metastasis observed one 2 patient t3 tumor died peritoneal metastases 15 months resection pse improve overall survival 77 58 21 1 3 5 years respectively compared patients pse 78 55 33 1 3 5 years respectively p 0 37 eight percent patients developed incisional hernia port site excision conclusion patients igbc pse associated improved survival considered mandatory definitive surgical treatment pubmed","probabilities":0.9799733,"Title":"Is port-site resection necessary in the surgical management of gallbladder cancer?","Abstract":"INTRODUCTION: Gallbladder carcinoma is frequently discovered incidentally on pathologic examination of the specimen after laparoscopic cholecystectomy (LC) performed for presumed \"benign\" disease. The objective of the present study was to assess the role of excision of port-sites from the initial LC for patients with incidental gallbladder carcinoma (IGBC) in a French registry. METHODS: Data on patients with IGBC identified after LC between 1998 and 2008 were retrospectively collated in a French multicenter database. Among those patients undergoing re-operation with curative intent, patients with port-site excision (PSE) were compared with patients without PSE and analyzed for differences in recurrence patterns and survival. RESULTS: Among 218 patients with IGBC after LC (68 men, 150 women, median age 64 years), 148 underwent re-resection with curative intent; 54 patients had PSE and 94 did not. Both groups were comparable with regard to demographic data (gender, age > 70, co-morbidities), surgical procedures (major resection, lymphadenectomy, main bile duct resection) and postoperative morbidity. In the PSE group, depth of tumor invasion was T1b in six, T2 in 24, T3 in 22, and T4 in two; this was not significantly different from patients without PSE (P = 0.69). Port-site metastasis was observed in only one (2%) patient with a T3 tumor who died with peritoneal metastases 15 months after resection. PSE did not improve the overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively) compared to patients with no PSE (78%, 55%, 33% at 1, 3, 5 years, respectively, P = 0.37). Eight percent of patients developed incisional hernia at the port-site after excision. CONCLUSION: In patients with IGBC, PSE was not associated with improved survival and should not be considered mandatory during definitive surgical treatment.","Source":"PubMed","category":"HUMAN","training_data":"Is port-site resection necessary in the surgical management of gallbladder cancer? INTRODUCTION: Gallbladder carcinoma is frequently discovered incidentally on pathologic examination of the specimen after laparoscopic cholecystectomy (LC) performed for presumed \"benign\" disease. The objective of the present study was to assess the role of excision of port-sites from the initial LC for patients with incidental gallbladder carcinoma (IGBC) in a French registry. METHODS: Data on patients with IGBC identified after LC between 1998 and 2008 were retrospectively collated in a French multicenter database. Among those patients undergoing re-operation with curative intent, patients with port-site excision (PSE) were compared with patients without PSE and analyzed for differences in recurrence patterns and survival. RESULTS: Among 218 patients with IGBC after LC (68 men, 150 women, median age 64 years), 148 underwent re-resection with curative intent; 54 patients had PSE and 94 did not. Both groups were comparable with regard to demographic data (gender, age > 70, co-morbidities), surgical procedures (major resection, lymphadenectomy, main bile duct resection) and postoperative morbidity. In the PSE group, depth of tumor invasion was T1b in six, T2 in 24, T3 in 22, and T4 in two; this was not significantly different from patients without PSE (P = 0.69). Port-site metastasis was observed in only one (2%) patient with a T3 tumor who died with peritoneal metastases 15 months after resection. PSE did not improve the overall survival (77%, 58%, 21% at 1, 3, 5 years, respectively) compared to patients with no PSE (78%, 55%, 33% at 1, 3, 5 years, respectively, P = 0.37). Eight percent of patients developed incisional hernia at the port-site after excision. CONCLUSION: In patients with IGBC, PSE was not associated with improved survival and should not be considered mandatory during definitive surgical treatment. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative platelet lymphocyte ratio predictor prognosis patients ampullary carcinoma aim emphasize significance platelet lymphocyte ratio plr estimating postoperative prognosis survival measures patients carcinoma ampulla vater methods retrospectively reviewed 82 patients underwent pancreaticoduodenectomy ampullary carcinoma july 2001 april 2014 investigated predictive significance preoperative plr disease free survival dfs overall survival os possible correlations plr clinical pathological features also evaluated results 5 year dfs os rates patients carcinoma ampulla vater pancreaticoduodenectomy 51 64 respectively multivariate analysis revealed significantly worse os patients plr 212 hazard ratio hr 3 446 95 confidence interval ci 1 4 8 43 p 0 007 lymphovascular invasion hr 2 973 95 ci 1 25 7 03 p 0 013 pathological stage pt3 4 hr 2 761 95 ci 1 7 1 p 0 035 similarly dfs significantly worse patients lymphovascular invasion hr 2 24 95 ci 1 1 4 56 p 0 025 stage pt3 4 hr 2 243 95 ci 1 03 4 84 p 0 04 conclusion preoperative plr shows predictive significance prognosis postoperative patients carcinoma ampulla vater suggest predictive value plr used development approaches monitor manage patients poor prognosis tab 4 fig 1 ref 45 pubmed","probabilities":0.9799733,"Title":"Preoperative platelet-to-lymphocyte ratio is a predictor of prognosis in patients with ampullary carcinoma","Abstract":"AIM: To emphasize the significance of the platelet-to-lymphocyte ratio (PLR) in estimating the postoperative prognosis or survival measures in patients with carcinoma of the ampulla of Vater. METHODS: We retrospectively reviewed 82 patients, who underwent pancreaticoduodenectomy for ampullary carcinoma between July 2001 and April 2014. We investigated the predictive significance of the preoperative PLR for disease-free survival (DFS) or overall survival (OS). The possible correlations between the PLR and clinical or pathological features were also evaluated. RESULTS: The 5-year DFS and OS rates of the patients with carcinoma of the ampulla of Vater after pancreaticoduodenectomy were 51 % and 64 %, respectively. Multivariate analysis revealed a significantly worse OS in patients with a PLR ≥ 212 [hazard ratio (HR): 3.446; 95% confidence interval (CI): 1.4-8.43; p = 0.007], lymphovascular invasion (HR: 2.973; 95% CI: 1.25-7.03; p = 0.013), or pathological stage pT3/4 (HR: 2.761; 95% CI: 1-7.1; p = 0.035). Similarly, DFS was significantly worse in patients with lymphovascular invasion (HR: 2.24; 95% CI: 1.1-4.56; p = 0.025) or stage pT3/4 (HR: 2.243; 95% CI, 1.03-4.84; p = 0.04). CONCLUSION: The preoperative PLR shows a predictive significance for the prognosis of postoperative patients with carcinoma of the ampulla of Vater. We suggest that because of its predictive value, the PLR can be used in the development of further approaches to monitor and manage patients with poor prognosis Tab. 4, Fig. 1, Ref. 45).","Source":"PubMed","category":"HUMAN","training_data":"Preoperative platelet-to-lymphocyte ratio is a predictor of prognosis in patients with ampullary carcinoma AIM: To emphasize the significance of the platelet-to-lymphocyte ratio (PLR) in estimating the postoperative prognosis or survival measures in patients with carcinoma of the ampulla of Vater. METHODS: We retrospectively reviewed 82 patients, who underwent pancreaticoduodenectomy for ampullary carcinoma between July 2001 and April 2014. We investigated the predictive significance of the preoperative PLR for disease-free survival (DFS) or overall survival (OS). The possible correlations between the PLR and clinical or pathological features were also evaluated. RESULTS: The 5-year DFS and OS rates of the patients with carcinoma of the ampulla of Vater after pancreaticoduodenectomy were 51 % and 64 %, respectively. Multivariate analysis revealed a significantly worse OS in patients with a PLR ≥ 212 [hazard ratio (HR): 3.446; 95% confidence interval (CI): 1.4-8.43; p = 0.007], lymphovascular invasion (HR: 2.973; 95% CI: 1.25-7.03; p = 0.013), or pathological stage pT3/4 (HR: 2.761; 95% CI: 1-7.1; p = 0.035). Similarly, DFS was significantly worse in patients with lymphovascular invasion (HR: 2.24; 95% CI: 1.1-4.56; p = 0.025) or stage pT3/4 (HR: 2.243; 95% CI, 1.03-4.84; p = 0.04). CONCLUSION: The preoperative PLR shows a predictive significance for the prognosis of postoperative patients with carcinoma of the ampulla of Vater. We suggest that because of its predictive value, the PLR can be used in the development of further approaches to monitor and manage patients with poor prognosis Tab. 4, Fig. 1, Ref. 45). PubMed","prediction_labels":"HUMAN"},{"cleaned":"axitinib ag 013736 oral specific vegfr tki shows potential therapeutic utility cholangiocarcinoma objective cholangiocarcinoma refractory cancer whose incidence increasing worldwide recent years neoangiogenesis plays important role growth various solid cancers including cholangiocarcinoma vascular endothelial growth factor plays important role tumor induced angiogenesis expression associated progression prognosis cholangiocarcinoma study examined whether axitinib ag 013736 inlyta potent selective second generation inhibitor vascular endothelial growth factor receptors 1 2 3 potentially useful therapeutic agent cholangiocarcinoma methods performed expression profiling angiogenesis related molecules eight cholangiocarcinoma cell lines found three showed high vascular endothelial growth factor expression among examined vivo anti tumor effect axitinib ncc bd1 gemcitabine sensitive extra hepatic cholangiocarcinoma cell line tkkk gemcitabine resistant intra hepatic cholangiocarcinoma cell line using subcutaneous xenograft models results oral administration axitinib significantly inhibited growth tkkk xenografts dose 6 mg kg 1 day 1 p 0 05 growth ncc bd1 xenografts 30 mg kg 1 day 1 p 0 05 treated tumors showed significant decrease microvessel density tumor cell proliferation index mild significant increase apoptotic index comparison untreated tumors conclusions results suggest axitinib promising therapy vascular endothelial growth factor expressing cholangiocarcinoma irrespective tumor origin gemcitabine sensitivity stn","probabilities":0.9467213,"Title":"Axitinib (Ag-013736) An Oral Specific Vegfr Tki Shows Potential Therapeutic Utility Against Cholangiocarcinoma","Abstract":"Objective: Cholangiocarcinoma is a refractory cancer whose incidence has been increasing worldwide in recent years. Neoangiogenesis plays an important role in the growth of various solid cancers, including cholangiocarcinoma. Vascular endothelial growth factor plays an important role in tumor-induced angiogenesis and its expression is associated with the progression and prognosis of cholangiocarcinoma. This study examined whether axitinib (AG-013736, INLYTA(®)), a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3, could be a potentially useful therapeutic agent for cholangiocarcinoma. \r\n\r\n Methods: We performed expression profiling of angiogenesis-related molecules in eight cholangiocarcinoma cell lines and found that three of them showed high vascular endothelial growth factor expression. Among them, we examined the in vivo anti-tumor effect of axitinib on NCC-BD1 (a gemcitabine-sensitive extra-hepatic cholangiocarcinoma cell line) and TKKK (a gemcitabine-resistant intra-hepatic cholangiocarcinoma cell line) using subcutaneous xenograft models. \r\n\r\n Results: Oral administration of axitinib significantly inhibited the growth of TKKK xenografts at a dose of 6 mg kg(-1) day(-1) (P<0.05), and the growth of NCC-BD1 xenografts at 30 mg kg(-1)day(-1) (P<0.05). Treated tumors showed a significant decrease of microvessel density and the tumor cell proliferation index and a mild but significant increase of the apoptotic index in comparison with untreated tumors. \r\n\r\n Conclusions: Our results suggest that axitinib should be a promising therapy for vascular endothelial growth factor-expressing cholangiocarcinoma, irrespective of tumor origin and gemcitabine sensitivity.","Source":"STN","category":"ANIMAL","training_data":"Axitinib (Ag-013736) An Oral Specific Vegfr Tki Shows Potential Therapeutic Utility Against Cholangiocarcinoma Objective: Cholangiocarcinoma is a refractory cancer whose incidence has been increasing worldwide in recent years. Neoangiogenesis plays an important role in the growth of various solid cancers, including cholangiocarcinoma. Vascular endothelial growth factor plays an important role in tumor-induced angiogenesis and its expression is associated with the progression and prognosis of cholangiocarcinoma. This study examined whether axitinib (AG-013736, INLYTA(®)), a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3, could be a potentially useful therapeutic agent for cholangiocarcinoma. \r\n\r\n Methods: We performed expression profiling of angiogenesis-related molecules in eight cholangiocarcinoma cell lines and found that three of them showed high vascular endothelial growth factor expression. Among them, we examined the in vivo anti-tumor effect of axitinib on NCC-BD1 (a gemcitabine-sensitive extra-hepatic cholangiocarcinoma cell line) and TKKK (a gemcitabine-resistant intra-hepatic cholangiocarcinoma cell line) using subcutaneous xenograft models. \r\n\r\n Results: Oral administration of axitinib significantly inhibited the growth of TKKK xenografts at a dose of 6 mg kg(-1) day(-1) (P<0.05), and the growth of NCC-BD1 xenografts at 30 mg kg(-1)day(-1) (P<0.05). Treated tumors showed a significant decrease of microvessel density and the tumor cell proliferation index and a mild but significant increase of the apoptotic index in comparison with untreated tumors. \r\n\r\n Conclusions: Our results suggest that axitinib should be a promising therapy for vascular endothelial growth factor-expressing cholangiocarcinoma, irrespective of tumor origin and gemcitabine sensitivity. STN","prediction_labels":"ANIMAL"},{"cleaned":"intra arterial therapy advanced intrahepatic cholangiocarcinoma multi institutional analysis background many patients intrahepatic cholangiocarcinoma icc present advanced inoperable disease data safety efficacy intra arterial therapy iat icc limited methods 1992 2012 total 198 patients advanced icc treated iat retrospectively identified databases five major hepatobiliary institutions data clinicopathological factors morbidity response rates overall survival collected analyzed results median patient age 61 years median tumor size 8 1 cm 47 5 patients solitary lesion iat consisted conventional transarterial chemoembolization ctace 64 7 drug eluting beads deb 5 6 bland embolization tae 6 6 yttrium 90 radioembolization 23 2 median number iat sessions 2 range 1 8 median time iat sessions 48 days periprocedural morbidity 29 8 complications minor n 43 however 16 patients grade 3 4 complication assessment tumor response revealed complete partial response 25 5 patients 61 5 stable disease 13 0 progressive disease median overall survival 13 2 months differ basis type iat ctace 13 4 months vs deb 10 5 months vs tae 14 3 months vs yttrium 90 11 3 months p 0 46 iat response modified response evaluation criteria solid tumors mrecist hazard ratio complete partial response 0 49 95 confidence interval 0 30 0 81 p 0 001 independently associated better survival conclusions iat icc safe led stable disease partial complete response three quarters patients among patients iat response overall survival prolonged role iat therapy icc warrants prospective evaluation clinical trials pubmed","probabilities":0.9799733,"Title":"Intra-arterial therapy for advanced intrahepatic cholangiocarcinoma: a multi-institutional analysis","Abstract":"BACKGROUND: Many patients with intrahepatic cholangiocarcinoma (ICC) present with advanced and inoperable disease. Data on the safety and efficacy of intra-arterial therapy (IAT) for ICC are limited. METHODS: Between 1992 and 2012, a total of 198 patients with advanced ICC treated with IAT were retrospectively identified from the databases of five major hepatobiliary institutions. Data on clinicopathological factors, morbidity, response rates, and overall survival were collected and analyzed. RESULTS: Median patient age was 61 years. Median tumor size was 8.1 cm, and 47.5% patients had a solitary lesion. IAT consisted of conventional transarterial chemoembolization (cTACE) (64.7%), drug-eluting beads (DEB) (5.6%), bland embolization (TAE) (6.6%), or yttrium-90 radioembolization (23.2%). Median number of IAT sessions was 2 (range 1-8). The median time between IAT sessions was 48 days. The periprocedural morbidity was 29.8%; most complications were minor (n = 43); however, 16 patients had a grade 3-4 complication. Assessment of tumor response revealed complete or partial response in 25.5% patients, while 61.5% had stable disease; 13.0% had progressive disease. Median overall survival was 13.2 months and did not differ on the basis of the type of IAT (cTACE, 13.4 months vs. DEB 10.5 months vs. TAE, 14.3 months vs. yttrium-90, 11.3 months; P = 0.46). IAT response on modified response evaluation criteria in solid tumors (mRECIST; hazard ratio for complete-partial response 0.49, 95% confidence interval 0.30-0.81; P < 0.001) was independently associated with better survival. CONCLUSIONS: IAT for ICC was safe and led to stable disease or partial to complete response in up to three-quarters of patients. Among patients with an IAT response, overall survival was prolonged. The role of IAT therapy for ICC warrants further prospective evaluation in clinical trials.","Source":"PubMed","category":"HUMAN","training_data":"Intra-arterial therapy for advanced intrahepatic cholangiocarcinoma: a multi-institutional analysis BACKGROUND: Many patients with intrahepatic cholangiocarcinoma (ICC) present with advanced and inoperable disease. Data on the safety and efficacy of intra-arterial therapy (IAT) for ICC are limited. METHODS: Between 1992 and 2012, a total of 198 patients with advanced ICC treated with IAT were retrospectively identified from the databases of five major hepatobiliary institutions. Data on clinicopathological factors, morbidity, response rates, and overall survival were collected and analyzed. RESULTS: Median patient age was 61 years. Median tumor size was 8.1 cm, and 47.5% patients had a solitary lesion. IAT consisted of conventional transarterial chemoembolization (cTACE) (64.7%), drug-eluting beads (DEB) (5.6%), bland embolization (TAE) (6.6%), or yttrium-90 radioembolization (23.2%). Median number of IAT sessions was 2 (range 1-8). The median time between IAT sessions was 48 days. The periprocedural morbidity was 29.8%; most complications were minor (n = 43); however, 16 patients had a grade 3-4 complication. Assessment of tumor response revealed complete or partial response in 25.5% patients, while 61.5% had stable disease; 13.0% had progressive disease. Median overall survival was 13.2 months and did not differ on the basis of the type of IAT (cTACE, 13.4 months vs. DEB 10.5 months vs. TAE, 14.3 months vs. yttrium-90, 11.3 months; P = 0.46). IAT response on modified response evaluation criteria in solid tumors (mRECIST; hazard ratio for complete-partial response 0.49, 95% confidence interval 0.30-0.81; P < 0.001) was independently associated with better survival. CONCLUSIONS: IAT for ICC was safe and led to stable disease or partial to complete response in up to three-quarters of patients. Among patients with an IAT response, overall survival was prolonged. The role of IAT therapy for ICC warrants further prospective evaluation in clinical trials. PubMed","prediction_labels":"HUMAN"},{"cleaned":"optimal extent surgical pathologic lymph node evaluation resected intrahepatic cholangiocarcinoma background lymph node ln status important predictor overall survival resected ihcc yet guidelines extent ln dissection evidence based evaluated whether number lns resected time surgery associated overall survival ihcc methods patients undergoing curative intent r0 r1 resection ihcc 2004 2012 identified within us national cancer database ln thresholds evaluated using maximal chi square testing five year overall survival modeled using kaplan meier cox regressions results 57 n 1 132 2 000 patients one lns resected pathologically examined 631 patients undergoing r0 resection pn0 disease maximal chi square testing identified 3 lns threshold closely associated overall survival 39 resections reached threshold multivariable survival analysis threshold lns associated overall survival including 3 lns p 0 186 current american joint committee cancer recommendation 6 lns p 0 318 conclusion determining extent lymphadenectomy time curative intent resection ihcc surgeons carefully consider prognostic yield absence overall survival benefit pubmed","probabilities":0.9799733,"Title":"Optimal extent of surgical and pathologic lymph node evaluation for resected intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Lymph node (LN) status is an important predictor of overall survival for resected IHCC, yet guidelines for the extent of LN dissection are not evidence-based. We evaluated whether the number of LNs resected at the time of surgery is associated with overall survival for IHCC. METHODS: Patients undergoing curative-intent (R0 or R1) resection for IHCC between 2004 and 2012 were identified within the US National Cancer Database. LN thresholds were evaluated using maximal chi-square testing and five-year overall survival was modeled using Kaplan-Meier and Cox regressions. RESULTS: 57% (n = 1,132) of 2,000 patients had one or more LNs resected and pathologically examined. In the 631 patients undergoing R0 resection with pN0 disease, maximal chi-square testing identified ≥3 LNs as the threshold most closely associated with overall survival. Only 39% of resections reached this threshold. On multivariable survival analysis, no threshold of LNs was associated with overall survival, including ≥3 LNs (p = 0.186) and the current American Joint Committee on Cancer recommendation of ≥6 LNs (p = 0.318). CONCLUSION: In determining the extent of lymphadenectomy at the time of curative-intent resection for IHCC, surgeons should carefully consider the prognostic yield in the absence of overall survival benefit.","Source":"PubMed","category":"HUMAN","training_data":"Optimal extent of surgical and pathologic lymph node evaluation for resected intrahepatic cholangiocarcinoma BACKGROUND: Lymph node (LN) status is an important predictor of overall survival for resected IHCC, yet guidelines for the extent of LN dissection are not evidence-based. We evaluated whether the number of LNs resected at the time of surgery is associated with overall survival for IHCC. METHODS: Patients undergoing curative-intent (R0 or R1) resection for IHCC between 2004 and 2012 were identified within the US National Cancer Database. LN thresholds were evaluated using maximal chi-square testing and five-year overall survival was modeled using Kaplan-Meier and Cox regressions. RESULTS: 57% (n = 1,132) of 2,000 patients had one or more LNs resected and pathologically examined. In the 631 patients undergoing R0 resection with pN0 disease, maximal chi-square testing identified ≥3 LNs as the threshold most closely associated with overall survival. Only 39% of resections reached this threshold. On multivariable survival analysis, no threshold of LNs was associated with overall survival, including ≥3 LNs (p = 0.186) and the current American Joint Committee on Cancer recommendation of ≥6 LNs (p = 0.318). CONCLUSION: In determining the extent of lymphadenectomy at the time of curative-intent resection for IHCC, surgeons should carefully consider the prognostic yield in the absence of overall survival benefit. PubMed","prediction_labels":"HUMAN"},{"cleaned":"squamous cell adenosquamous carcinomas gallbladder clinicopathological analysis 34 cases identified 606 carcinomas information literature squamous cell adenosquamous carcinomas gallbladder highly limited study 606 resected invasive gallbladder carcinoma cases analyzed squamous differentiation identified 41 cases 7 without identifiable glandular type invasive component classified pure squamous cell carcinomas 8 cases squamous component constituting 25 99 tumors classified adenosquamous carcinomas 26 cases included analysis remaining 7 25 squamous component classified adenocarcinoma focal squamous change excluded clinicopathological characteristics adenosquamous carcinoma squamous cell carcinomas documented contrasted ordinary gallbladder adenocarcinomas average patient age 65 years range 26 81 female male ratio 3 8 13 preoperative clinical suspicion malignancy grossly 58 presented thickening hardening wall 6 polypoid 12 mucosa adjacent tumor revealed squamous metaplasia pure squamous cell carcinomas prominent keratinization giant cells tumor infiltrating eosinophils observed 29 51 squamous cell carcinomas adenosquamous carcinomas versus 10 p 0 02 6 p 0 001 gallbladder adenocarcinomas respectively three cases advanced pt2 carcinomas follow available 31 patients 25 died disease median 5 months range 0 20 6 alive median 64 months range 5 112 5 survival patients squamous cell carcinomas adenosquamous carcinomas significantly worse gallbladder adenocarcinomas p 0 003 adverse prognosis persisted compared stage matched advanced gallbladder adenocarcinoma cases median 11 4 months p 0 01 conclusion squamous differentiation noted 7 gallbladder carcinomas incidence adenosquamous carcinoma defined 25 99 tumor squamous 4 pure squamous cell carcinoma without documented invasive glandular component 1 pure squamous cell carcinomas often showed prominent keratinization overall prognosis adenosquamous carcinoma squamous cell carcinoma appears even worse ordinary adenocarcinomas patients died within months however alive beyond 2 years cohort experienced long term survival pubmed","probabilities":0.962963,"Title":"Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas","Abstract":"The information in the literature on squamous cell and adenosquamous carcinomas of the gallbladder is highly limited. In this study, 606 resected invasive gallbladder carcinoma cases were analyzed. Squamous differentiation was identified in 41 cases (7%). Those without any identifiable glandular-type invasive component were classified as pure squamous cell carcinomas (8 cases) and those with the squamous component constituting 25-99% of the tumors were classified as adenosquamous carcinomas (26 cases) and included into the analysis. The remaining 7 that had <25% squamous component were classified as adenocarcinoma with focal squamous change and excluded. The clinicopathological characteristics of adenosquamous carcinoma/squamous cell carcinomas were documented and contrasted with that of ordinary gallbladder adenocarcinomas. The average patient age was 65 years (range 26-81); female/male ratio, 3.8. In only 13%, there was a preoperative clinical suspicion of malignancy. Grossly, 58% presented as thickening and hardening of the wall and 6% were polypoid. In 12%, mucosa adjacent to the tumor revealed squamous metaplasia. All pure squamous cell carcinomas had prominent keratinization. Giant cells and tumor-infiltrating eosinophils were observed in 29 and 51% of the squamous cell carcinomas/adenosquamous carcinomas versus 10% (P=0.02) and 6% (P=0.001) in gallbladder adenocarcinomas, respectively. All but three cases had 'advanced' (pT2 and above) carcinomas. Follow-up was available in 31 patients: 25 died of disease (median=5 months, range 0-20), and 6 were alive (median=64 months, range 5-112.5). The survival of patients with squamous cell carcinomas/adenosquamous carcinomas was significantly worse than that of gallbladder adenocarcinomas (P=0.003), and this adverse prognosis persisted when compared with stage-matched advanced gallbladder adenocarcinoma cases (median=11.4 months, P=0.01). In conclusion, squamous differentiation was noted in 7% of gallbladder carcinomas. The incidence of adenosquamous carcinoma (defined as 25-99% of the tumor being squamous) was 4%, and that of pure squamous cell carcinoma (without any documented invasive glandular component) was 1%. Pure squamous cell carcinomas often showed prominent keratinization. The overall prognosis of adenosquamous carcinoma/squamous cell carcinoma appears to be even worse than that of ordinary adenocarcinomas. Most patients died within a few months; however, those few who were alive beyond 2 years in this cohort experienced long-term survival.","Source":"PubMed","category":"HUMAN","training_data":"Squamous cell and adenosquamous carcinomas of the gallbladder: clinicopathological analysis of 34 cases identified in 606 carcinomas The information in the literature on squamous cell and adenosquamous carcinomas of the gallbladder is highly limited. In this study, 606 resected invasive gallbladder carcinoma cases were analyzed. Squamous differentiation was identified in 41 cases (7%). Those without any identifiable glandular-type invasive component were classified as pure squamous cell carcinomas (8 cases) and those with the squamous component constituting 25-99% of the tumors were classified as adenosquamous carcinomas (26 cases) and included into the analysis. The remaining 7 that had <25% squamous component were classified as adenocarcinoma with focal squamous change and excluded. The clinicopathological characteristics of adenosquamous carcinoma/squamous cell carcinomas were documented and contrasted with that of ordinary gallbladder adenocarcinomas. The average patient age was 65 years (range 26-81); female/male ratio, 3.8. In only 13%, there was a preoperative clinical suspicion of malignancy. Grossly, 58% presented as thickening and hardening of the wall and 6% were polypoid. In 12%, mucosa adjacent to the tumor revealed squamous metaplasia. All pure squamous cell carcinomas had prominent keratinization. Giant cells and tumor-infiltrating eosinophils were observed in 29 and 51% of the squamous cell carcinomas/adenosquamous carcinomas versus 10% (P=0.02) and 6% (P=0.001) in gallbladder adenocarcinomas, respectively. All but three cases had 'advanced' (pT2 and above) carcinomas. Follow-up was available in 31 patients: 25 died of disease (median=5 months, range 0-20), and 6 were alive (median=64 months, range 5-112.5). The survival of patients with squamous cell carcinomas/adenosquamous carcinomas was significantly worse than that of gallbladder adenocarcinomas (P=0.003), and this adverse prognosis persisted when compared with stage-matched advanced gallbladder adenocarcinoma cases (median=11.4 months, P=0.01). In conclusion, squamous differentiation was noted in 7% of gallbladder carcinomas. The incidence of adenosquamous carcinoma (defined as 25-99% of the tumor being squamous) was 4%, and that of pure squamous cell carcinoma (without any documented invasive glandular component) was 1%. Pure squamous cell carcinomas often showed prominent keratinization. The overall prognosis of adenosquamous carcinoma/squamous cell carcinoma appears to be even worse than that of ordinary adenocarcinomas. Most patients died within a few months; however, those few who were alive beyond 2 years in this cohort experienced long-term survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"downregulated expression tropomyosin 1 intrahepatic cholangiocarcinoma predictor recurrence prognosis background downregulation tropomyosin 1 tpm1 observed various tumors studies focused clinical significance tpm1 intrahepatic cholangiocarcinoma icc present study investigated prognostic significance tpm1 icc material methods total 124 patients icc enrolled study quantitative real time polymerase chain reaction qrt rcr performed examine mrna levels tpm1 icc tissue samples adjacent noncancerous tissue specimens protein level tpm1 tissue specimens investigated using immunohistochemistry assay correlation tpm1 clinicopathological features icc analyzed chi square test survival analysis performed kaplan meier method cox proportional hazards model used evaluate prognostic value tpm1 patients icc results tpm1 expression significantly downregulated icc tissues mrna protein levels p 0 001 downregulated tpm1 mrna negatively associated tumor size p 0 001 tnm stage p 0 007 moreover survival analysis demonstrated patients low tpm1 expression shorter overall survival os p 0 001 recurrence free survival rfs p 0 001 high tpm1 expression additionally multivariate analysis showed tpm1 potential biomarker predicting recurrence hr 4 632 95 ci 3 832 10 368 p 0 001 survival outcome hr 5 320 95 ci 2 627 11 776 p 0 001 icc conclusions tpm1 may serve useful biomarker predicting tumor recurrence prognosis patients icc stn","probabilities":0.88235295,"Title":"Downregulated Expression Of Tropomyosin 1 In Intrahepatic Cholangiocarcinoma: A Predictor Of Recurrence And Prognosis","Abstract":"BACKGROUND The downregulation of tropomyosin 1 (TPM1) has been observed in various tumors, but few studies have focused on the clinical significance of TPM1 in intrahepatic cholangiocarcinoma (ICC). In the present study, we investigated the prognostic significance of TPM1 in ICC. MATERIAL AND METHODS A total of 124 patients with ICC were enrolled in this study. Quantitative real-time polymerase chain reaction (qRT-RCR) was performed to examine the mRNA levels of TPM1 in ICC tissue samples and adjacent noncancerous tissue specimens, while the protein level of TPM1 in tissue specimens were investigated using immunohistochemistry assay. The correlation of TPM1 with clinicopathological features of ICC was analyzed by chi-square test. Survival analysis was performed with Kaplan-Meier method. The Cox proportional hazards model was used to evaluate the prognostic value of TPM1 in patients with ICC. RESULTS TPM1 expression was significantly downregulated in ICC tissues at mRNA and protein levels (P<0.001 for both). Downregulated TPM1 mRNA was negatively associated with tumor size (P=0.001) and TNM stage (P=0.007). Moreover, survival analysis demonstrated that patients with low TPM1 expression had a shorter overall survival (OS) (P<0.001) and recurrence-free survival (RFS) (P<0.001) than those with high TPM1 expression. Additionally, multivariate analysis showed that TPM1 could be a potential biomarker for predicting the recurrence (HR=4.632, 95% CI: 3.832-10.368, P<0.001) and survival outcome (HR=5.320, 95% CI: 2.627-11.776, P<0.001) of ICC. CONCLUSIONS TPM1 may serve as a useful biomarker for predicting tumor recurrence and prognosis in patients with ICC.","Source":"STN","category":"HUMAN","training_data":"Downregulated Expression Of Tropomyosin 1 In Intrahepatic Cholangiocarcinoma: A Predictor Of Recurrence And Prognosis BACKGROUND The downregulation of tropomyosin 1 (TPM1) has been observed in various tumors, but few studies have focused on the clinical significance of TPM1 in intrahepatic cholangiocarcinoma (ICC). In the present study, we investigated the prognostic significance of TPM1 in ICC. MATERIAL AND METHODS A total of 124 patients with ICC were enrolled in this study. Quantitative real-time polymerase chain reaction (qRT-RCR) was performed to examine the mRNA levels of TPM1 in ICC tissue samples and adjacent noncancerous tissue specimens, while the protein level of TPM1 in tissue specimens were investigated using immunohistochemistry assay. The correlation of TPM1 with clinicopathological features of ICC was analyzed by chi-square test. Survival analysis was performed with Kaplan-Meier method. The Cox proportional hazards model was used to evaluate the prognostic value of TPM1 in patients with ICC. RESULTS TPM1 expression was significantly downregulated in ICC tissues at mRNA and protein levels (P<0.001 for both). Downregulated TPM1 mRNA was negatively associated with tumor size (P=0.001) and TNM stage (P=0.007). Moreover, survival analysis demonstrated that patients with low TPM1 expression had a shorter overall survival (OS) (P<0.001) and recurrence-free survival (RFS) (P<0.001) than those with high TPM1 expression. Additionally, multivariate analysis showed that TPM1 could be a potential biomarker for predicting the recurrence (HR=4.632, 95% CI: 3.832-10.368, P<0.001) and survival outcome (HR=5.320, 95% CI: 2.627-11.776, P<0.001) of ICC. CONCLUSIONS TPM1 may serve as a useful biomarker for predicting tumor recurrence and prognosis in patients with ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"predictive factors gastroduodenal bleeding postoperative radiotherapy biliary tract cancer objective identify predictive factors gastroduodenal bleeding postoperative radiation therapy patients biliary tract cancer methods identified 186 patients biliary tract cancer completed scheduled postoperative radiation therapy march 2000 august 2013 isolate effects radiation gastroduodenal bleeding patients pylorus preserving pancreaticoduodenectomy pylorus resecting pancreaticoduodenectomy whipple surgery n 67 excluded analysis postoperative radiation therapy started median 5 weeks range 4 12 weeks surgery median dose 44 gy range 44 54 chemotherapy also concurrently administered 102 patients results median age patients 59 years range 36 76 years 119 patients 26 intrahepatic cholangiocarcinoma 29 hilar cholangiocarcinoma 64 extrahepatic tumors gallbladder cancer n 53 proximal bile duct cancer n 10 choledochal cyst cancer n 1 11 patients 9 developed gastroduodenal bleeding univariate analyses hepatic artery resection gastroduodenal wall thickening postoperative radiation therapy simulation computed tomography statistically significant factors gastroduodenal bleeding multivariate analysis logistic regression model using two variables revealed parameters independent predictors gastroduodenal bleeding conclusions concomitant hepatic artery resection presence gastroduodenal wall thickening postoperative radiation therapy simulation computed tomography predictive factors gastroduodenal bleeding postoperative radiation therapy biliary tract cancer cases patients informed high risk gastroduodenal bleeding closely observed postoperative radiation therapy stn","probabilities":0.9799733,"Title":"Predictive Factors Of Gastroduodenal Bleeding After Postoperative Radiotherapy In Biliary Tract Cancer","Abstract":"Objective: To identify predictive factors for gastroduodenal bleeding after postoperative radiation therapy in patients with biliary tract cancer. \r\n\r\n Methods: We identified 186 patients with biliary tract cancer who completed scheduled postoperative radiation therapy from March 2000 to August 2013. To isolate the effects of radiation on gastroduodenal bleeding, patients with pylorus-preserving pancreaticoduodenectomy, pylorus-resecting pancreaticoduodenectomy or Whipple surgery (n = 67) were excluded from this analysis. Postoperative radiation therapy was started at a median 5 weeks (range: 4-12 weeks) after surgery with a median dose of 44 Gy (range: 44-54), and chemotherapy was also concurrently administered to 102 patients. \r\n\r\n Results: The median age of the patients was 59 years (range: 36-76 years). Of the 119 patients, 26 had intrahepatic cholangiocarcinoma, 29 had hilar cholangiocarcinoma, while 64 had extrahepatic tumors (gallbladder cancer, n = 53; proximal bile duct cancer, n = 10; choledochal cyst cancer, n = 1). Of all, 11 patients (9%) developed gastroduodenal bleeding. In univariate analyses, hepatic artery resection and gastroduodenal wall thickening on postoperative radiation therapy simulation computed tomography were statistically significant factors for gastroduodenal bleeding. Multivariate analysis by a logistic regression model using those two variables revealed that both parameters were independent predictors for gastroduodenal bleeding. \r\n\r\n Conclusions: Concomitant hepatic artery resection and presence of gastroduodenal wall thickening on postoperative radiation therapy simulation computed tomography were predictive factors for gastroduodenal bleeding after postoperative radiation therapy in biliary tract cancer. In such cases, patients should be informed of the high risk of gastroduodenal bleeding, and should be closely observed during and after postoperative radiation therapy.","Source":"STN","category":"HUMAN","training_data":"Predictive Factors Of Gastroduodenal Bleeding After Postoperative Radiotherapy In Biliary Tract Cancer Objective: To identify predictive factors for gastroduodenal bleeding after postoperative radiation therapy in patients with biliary tract cancer. \r\n\r\n Methods: We identified 186 patients with biliary tract cancer who completed scheduled postoperative radiation therapy from March 2000 to August 2013. To isolate the effects of radiation on gastroduodenal bleeding, patients with pylorus-preserving pancreaticoduodenectomy, pylorus-resecting pancreaticoduodenectomy or Whipple surgery (n = 67) were excluded from this analysis. Postoperative radiation therapy was started at a median 5 weeks (range: 4-12 weeks) after surgery with a median dose of 44 Gy (range: 44-54), and chemotherapy was also concurrently administered to 102 patients. \r\n\r\n Results: The median age of the patients was 59 years (range: 36-76 years). Of the 119 patients, 26 had intrahepatic cholangiocarcinoma, 29 had hilar cholangiocarcinoma, while 64 had extrahepatic tumors (gallbladder cancer, n = 53; proximal bile duct cancer, n = 10; choledochal cyst cancer, n = 1). Of all, 11 patients (9%) developed gastroduodenal bleeding. In univariate analyses, hepatic artery resection and gastroduodenal wall thickening on postoperative radiation therapy simulation computed tomography were statistically significant factors for gastroduodenal bleeding. Multivariate analysis by a logistic regression model using those two variables revealed that both parameters were independent predictors for gastroduodenal bleeding. \r\n\r\n Conclusions: Concomitant hepatic artery resection and presence of gastroduodenal wall thickening on postoperative radiation therapy simulation computed tomography were predictive factors for gastroduodenal bleeding after postoperative radiation therapy in biliary tract cancer. In such cases, patients should be informed of the high risk of gastroduodenal bleeding, and should be closely observed during and after postoperative radiation therapy. STN","prediction_labels":"HUMAN"},{"cleaned":"hepatitis c virus infection risk intrahepatic cholangiocarcinoma extrahepatic cholangiocarcinoma evidence systematic review meta analysis 16 case control studies background studies investigating association hepatitis c virus hcv infections occurrence cholangiocarcinoma cca especially intrahepatic cholangiocarcinoma icc shown inconsistent findings although previous meta analyses referred hcv cca mainly focused icc rather cca extrahepatic cholangiocarcinoma ecc since relevant new studies published association hcv icc since different anatomic locations cca distinct epidemiologic features different risk factors necessary evaluate relationship hcv infection icc ecc cca methods relevant studies identified searching pubmed embase medline databases prior 1 august 2013 pooled risk estimates calculated random effects models using stata 11 0 results total 16 case control studies included final analysis pooled risk estimates showed statistically significant increasing risk cca odds ratio 5 44 95 ci 2 72 10 89 pooled risk estimate icc 3 38 95 ci 2 72 4 21 higher ecc 1 75 95 ci 1 00 3 05 subgroup analysis pooled risk estimate icc studies north america obviously higher asia 6 48 versus 2 01 begg funnel plot egger test showed evidence publication bias conclusions hcv infection associated increasing risk cca especially icc pubmed","probabilities":0.9799733,"Title":"Hepatitis C virus infection and the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma: evidence from a systematic review and meta-analysis of 16 case-control studies","Abstract":"BACKGROUND: Studies investigating the association between hepatitis C virus (HCV) infections and the occurrence of cholangiocarcinoma (CCA), especially intrahepatic cholangiocarcinoma (ICC), have shown inconsistent findings. Although previous meta-analyses referred to HCV and CCA, they mainly focused on ICC rather than CCA or extrahepatic cholangiocarcinoma (ECC). Since then, relevant new studies have been published on the association between HCV and ICC. Since the different anatomic locations of CCA have distinct epidemiologic features and different risk factors, it is necessary to evaluate the relationship between HCV infection and ICC, ECC, and CCA. METHODS: Relevant studies were identified by searching PUBMED, EMBASE, and MEDLINE databases prior to 1 August 2013. Pooled risk estimates were calculated with random-effects models using STATA 11.0. RESULTS: A total of 16 case-control studies were included in the final analysis. Pooled risk estimates showed a statistically significant increasing risk of CCA (odds ratio (OR) = 5.44, 95% CI, 2.72 to 10.89). The pooled risk estimate of ICC (OR = 3.38, 95% CI, 2.72 to 4.21) was higher than that of ECC (OR = 1.75, 95% CI, 1.00 to 3.05). In a subgroup analysis, the pooled risk estimate of ICC in studies from North America was obviously higher than in Asia (6.48 versus 2.01). The Begg funnel plot and Egger test showed no evidence of publication bias. CONCLUSIONS: HCV infection is associated with the increasing risk of CCA, especially ICC.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis C virus infection and the risk of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma: evidence from a systematic review and meta-analysis of 16 case-control studies BACKGROUND: Studies investigating the association between hepatitis C virus (HCV) infections and the occurrence of cholangiocarcinoma (CCA), especially intrahepatic cholangiocarcinoma (ICC), have shown inconsistent findings. Although previous meta-analyses referred to HCV and CCA, they mainly focused on ICC rather than CCA or extrahepatic cholangiocarcinoma (ECC). Since then, relevant new studies have been published on the association between HCV and ICC. Since the different anatomic locations of CCA have distinct epidemiologic features and different risk factors, it is necessary to evaluate the relationship between HCV infection and ICC, ECC, and CCA. METHODS: Relevant studies were identified by searching PUBMED, EMBASE, and MEDLINE databases prior to 1 August 2013. Pooled risk estimates were calculated with random-effects models using STATA 11.0. RESULTS: A total of 16 case-control studies were included in the final analysis. Pooled risk estimates showed a statistically significant increasing risk of CCA (odds ratio (OR) = 5.44, 95% CI, 2.72 to 10.89). The pooled risk estimate of ICC (OR = 3.38, 95% CI, 2.72 to 4.21) was higher than that of ECC (OR = 1.75, 95% CI, 1.00 to 3.05). In a subgroup analysis, the pooled risk estimate of ICC in studies from North America was obviously higher than in Asia (6.48 versus 2.01). The Begg funnel plot and Egger test showed no evidence of publication bias. CONCLUSIONS: HCV infection is associated with the increasing risk of CCA, especially ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative serum ca 19 9 level predictive factor recurrence curative resection biliary tract cancer background complete surgical removal biliary tract cancer btc offers chance cure however long term survival remains limited frequent recurrence surgery purpose study evaluate whether preoperative serum carbohydrate antigen ca 19 9 level predict recurrence curative resection btc methods performed retrospective review medical records patients diagnosed btc underwent curative resection optimal cutoff value preoperative serum level ca 19 9 predicted recurrence determined roc curve preoperative postoperative risk factors recurrence evaluated using log rank test results total 101 patients eligible study optimal cutoff value preoperative serum ca 19 9 level predict recurrence 55 u ml forty five patients 44 6 experienced recurrence curative resection median follow period 28 4 months recurrence occurred 33 61 1 54 patients ca 19 9 levels 55 u ml compared 12 25 5 47 patients ca 19 9 levels 55 u ml recurrence rate significantly higher patients baseline ca 19 9 serum levels 55 u ml hazard ratio 3 282 95 confidence interval 1 684 6 395 p 0 001 conclusions elevated preoperative serum ca 19 9 associated high risk recurrence curative resection btc different treatment plans might needed patients btc high serum levels ca 19 9 pubmed","probabilities":0.9799733,"Title":"Preoperative serum CA 19-9 level as a predictive factor for recurrence after curative resection in biliary tract cancer","Abstract":"BACKGROUND: Complete surgical removal of biliary tract cancer (BTC) offers the only chance of cure; however, long-term survival remains very limited because of frequent recurrence after surgery. The purpose of our study was to evaluate whether the preoperative serum carbohydrate antigen (CA) 19-9 level could predict recurrence after curative resection of BTC. METHODS: We performed a retrospective review of the medical records of patients who were diagnosed with BTC and underwent curative resection. The optimal cutoff value for the preoperative serum level of CA 19-9 that predicted recurrence was determined by a ROC curve. Preoperative and postoperative risk factors for recurrence were evaluated using log-rank test. RESULTS: A total of 101 patients were eligible for this study. The optimal cutoff value of preoperative serum CA 19-9 level to predict recurrence was 55 U/mL. Forty-five patients (44.6%) experienced recurrence after curative resection with a median follow-up period of 28.4 months. Recurrence occurred in 33 (61.1%) of 54 patients with CA 19-9 levels ≥55 U/mL compared with only 12 (25.5%) of 47 patients with CA 19-9 levels <55 U/mL. The recurrence rate was significantly higher in patients with baseline CA 19-9 serum levels ≥55 U/mL (hazard ratio, 3.282; 95% confidence interval, 1.684-6.395; P < 0.001). CONCLUSIONS: Elevated preoperative serum CA 19-9 was associated with a high risk of recurrence after curative resection of BTC. Different treatment plans might be needed for patients with BTC and high serum levels of CA 19-9.","Source":"PubMed","category":"HUMAN","training_data":"Preoperative serum CA 19-9 level as a predictive factor for recurrence after curative resection in biliary tract cancer BACKGROUND: Complete surgical removal of biliary tract cancer (BTC) offers the only chance of cure; however, long-term survival remains very limited because of frequent recurrence after surgery. The purpose of our study was to evaluate whether the preoperative serum carbohydrate antigen (CA) 19-9 level could predict recurrence after curative resection of BTC. METHODS: We performed a retrospective review of the medical records of patients who were diagnosed with BTC and underwent curative resection. The optimal cutoff value for the preoperative serum level of CA 19-9 that predicted recurrence was determined by a ROC curve. Preoperative and postoperative risk factors for recurrence were evaluated using log-rank test. RESULTS: A total of 101 patients were eligible for this study. The optimal cutoff value of preoperative serum CA 19-9 level to predict recurrence was 55 U/mL. Forty-five patients (44.6%) experienced recurrence after curative resection with a median follow-up period of 28.4 months. Recurrence occurred in 33 (61.1%) of 54 patients with CA 19-9 levels ≥55 U/mL compared with only 12 (25.5%) of 47 patients with CA 19-9 levels <55 U/mL. The recurrence rate was significantly higher in patients with baseline CA 19-9 serum levels ≥55 U/mL (hazard ratio, 3.282; 95% confidence interval, 1.684-6.395; P < 0.001). CONCLUSIONS: Elevated preoperative serum CA 19-9 was associated with a high risk of recurrence after curative resection of BTC. Different treatment plans might be needed for patients with BTC and high serum levels of CA 19-9. PubMed","prediction_labels":"HUMAN"},{"cleaned":"inhibition hypoxia inducible factor 1 topoisomerase acriflavine sensitizes perihilar cholangiocarcinomas photodynamic therapy background photodynamic therapy pdt induces tumor cell death oxidative stress hypoxia also survival signaling activation hypoxia inducible factor 1 hif 1 since perihilar cholangiocarcinomas relatively recalcitrant pdt aims 1 determine expression levels hif 1 associated proteins human perihilar cholangiocarcinomas 2 investigate role hif 1 pdt treated human perihilar cholangiocarcinoma cells 3 determine whether hif 1 inhibition reduces survival signaling enhances pdt efficacy results increased expression vegf cd105 cd31 ki 67 glut 1 confirmed human perihilar cholangiocarcinomas pdt liposome delivered zinc phthalocyanine caused hif 1 stabilization sk cha 1 cells increased transcription hif 1 downstream genes acriflavine taken sk cha 1 cells translocated nucleus hypoxic conditions importantly pretreatment sk cha 1 cells acriflavine enhanced pdt efficacy via inhibition hif 1 topoisomerases ii methods expression vegf cd105 cd31 ki 67 glut 1 determined immunohistochemistry human perihilar cholangiocarcinomas addition response human perihilar cholangiocarcinoma sk cha 1 cells pdt liposome delivered zinc phthalocyanine investigated normoxic hypoxic conditions acriflavine hif 1 hif 1 dimerization inhibitor potential dual topoisomerase ii inhibitor evaluated adjuvant effect pdt efficacy conclusions hif 1 activated human hilar cholangiocarcinomas contributes tumor cell survival following pdt vitro combining pdt acriflavine pretreatment improves pdt efficacy cultured cells therefore warrants preclinical validation therapy recalcitrant perihilar cholangiocarcinomas stn","probabilities":0.9467213,"Title":"Inhibition Of Hypoxia Inducible Factor 1 And Topoisomerase With Acriflavine Sensitizes Perihilar Cholangiocarcinomas To Photodynamic Therapy","Abstract":"Background: Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of HIF-1-associated proteins in human perihilar cholangiocarcinomas, (2) investigate the role of HIF-1 in PDT-treated human perihilar cholangiocarcinoma cells, and (3) determine whether HIF-1 inhibition reduces survival signaling and enhances PDT efficacy. \r\n\r\n Results: Increased expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was confirmed in human perihilar cholangiocarcinomas. PDT with liposome-delivered zinc phthalocyanine caused HIF-1α stabilization in SK-ChA-1 cells and increased transcription of HIF-1α downstream genes. Acriflavine was taken up by SK-ChA-1 cells and translocated to the nucleus under hypoxic conditions. Importantly, pretreatment of SK-ChA-1 cells with acriflavine enhanced PDT efficacy via inhibition of HIF-1 and topoisomerases I and II. \r\n\r\n Methods: The expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was determined by immunohistochemistry in human perihilar cholangiocarcinomas. In addition, the response of human perihilar cholangiocarcinoma (SK-ChA-1) cells to PDT with liposome-delivered zinc phthalocyanine was investigated under both normoxic and hypoxic conditions. Acriflavine, a HIF-1α/HIF-1β dimerization inhibitor and a potential dual topoisomerase I/II inhibitor, was evaluated for its adjuvant effect on PDT efficacy. \r\n\r\n Conclusions: HIF-1, which is activated in human hilar cholangiocarcinomas, contributes to tumor cell survival following PDT in vitro. Combining PDT with acriflavine pretreatment improves PDT efficacy in cultured cells and therefore warrants further preclinical validation for therapy-recalcitrant perihilar cholangiocarcinomas.","Source":"STN","category":"ANIMAL","training_data":"Inhibition Of Hypoxia Inducible Factor 1 And Topoisomerase With Acriflavine Sensitizes Perihilar Cholangiocarcinomas To Photodynamic Therapy Background: Photodynamic therapy (PDT) induces tumor cell death by oxidative stress and hypoxia but also survival signaling through activation of hypoxia-inducible factor 1 (HIF-1). Since perihilar cholangiocarcinomas are relatively recalcitrant to PDT, the aims were to (1) determine the expression levels of HIF-1-associated proteins in human perihilar cholangiocarcinomas, (2) investigate the role of HIF-1 in PDT-treated human perihilar cholangiocarcinoma cells, and (3) determine whether HIF-1 inhibition reduces survival signaling and enhances PDT efficacy. \r\n\r\n Results: Increased expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was confirmed in human perihilar cholangiocarcinomas. PDT with liposome-delivered zinc phthalocyanine caused HIF-1α stabilization in SK-ChA-1 cells and increased transcription of HIF-1α downstream genes. Acriflavine was taken up by SK-ChA-1 cells and translocated to the nucleus under hypoxic conditions. Importantly, pretreatment of SK-ChA-1 cells with acriflavine enhanced PDT efficacy via inhibition of HIF-1 and topoisomerases I and II. \r\n\r\n Methods: The expression of VEGF, CD105, CD31/Ki-67, and GLUT-1 was determined by immunohistochemistry in human perihilar cholangiocarcinomas. In addition, the response of human perihilar cholangiocarcinoma (SK-ChA-1) cells to PDT with liposome-delivered zinc phthalocyanine was investigated under both normoxic and hypoxic conditions. Acriflavine, a HIF-1α/HIF-1β dimerization inhibitor and a potential dual topoisomerase I/II inhibitor, was evaluated for its adjuvant effect on PDT efficacy. \r\n\r\n Conclusions: HIF-1, which is activated in human hilar cholangiocarcinomas, contributes to tumor cell survival following PDT in vitro. Combining PDT with acriflavine pretreatment improves PDT efficacy in cultured cells and therefore warrants further preclinical validation for therapy-recalcitrant perihilar cholangiocarcinomas. STN","prediction_labels":"ANIMAL"},{"cleaned":"neoadjuvant chemoradiation followed surgery locally advanced gallbladder cancers new paradigm purpose locally advanced t3 t4 gallbladder cancers large fixed portal nodes dismal prognosis undertaken surgery entails extensive resections high morbidity therefore many centers patients offered palliative chemotherapy prospective study used neoadjuvant concurrent chemoradiation intention downstaging facilitating r0 resection tumors patients methods twenty eight patients locally advanced carcinoma gallbladder stage iii deep liver infiltrations large portal nodes underwent prior positron emission tomography computed tomography rule metastatic disease treated concomitant chemoradiation using helical tomotherapy dose 57 gy 25 fractions gross tumor 45 gy 25 fractions surrounding nodes injectable gemcitabine 300 mg m 2 week 5 weeks results 28 patients 25 89 successfully completed planned chemoradiation 20 71 achieved partial complete radiologic response eighteen 64 patients surgically explored 14 56 achieved r0 resection median follow 37 months surviving patients median overall survival os 20 months patients one patient recurred common bile duct postsurgery whereas six patients distant metastasis 5 year os 24 patients 47 patients r0 resection biliary leak seen 6 43 patients two required interventions conclusion locally advanced unresectable cancers may benefit neoadjuvant chemoradiation facilitate curative resection good survival pubmed","probabilities":0.9799733,"Title":"Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Gallbladder Cancers: A New Paradigm","Abstract":"PURPOSE: Locally advanced (T3/T4) gallbladder cancers with large fixed portal nodes have a dismal prognosis. If undertaken, surgery entails extensive resections with high morbidity; therefore, in many centers, patients are offered palliative chemotherapy. In this prospective study, we used neoadjuvant concurrent chemoradiation with the intention of downstaging and facilitating R0 resection of these tumors. PATIENTS AND METHODS: Twenty-eight patients with locally advanced carcinoma gallbladder (stage III, having deep liver infiltrations and/or large portal nodes) underwent prior positron emission tomography/computed tomography to rule out metastatic disease. All were treated with concomitant chemoradiation using helical tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor and 45 Gy over 25 fractions to the surrounding nodes) with injectable gemcitabine (300 mg/m(2)/week × 5 weeks). RESULTS: Of the 28 patients, 25 (89 %) successfully completed planned chemoradiation and 20 (71 %) achieved partial or complete radiologic response. Eighteen (64 %) patients were surgically explored, of whom 14 (56 %) achieved R0 resection. At the median follow-up of 37 months for the surviving patients, the median overall survival (OS) was 20 months for all patients. Only one patient recurred in the common bile duct postsurgery, whereas six patients had distant metastasis. The 5-year OS was 24 % for all patients and 47 % for patients with R0 resection. Biliary leak was seen in 6 (43 %) patients, of whom two required interventions. CONCLUSION: Locally advanced unresectable cancers may benefit from neoadjuvant chemoradiation to facilitate a curative resection with a good survival.","Source":"PubMed","category":"HUMAN","training_data":"Neoadjuvant Chemoradiation Followed by Surgery for Locally Advanced Gallbladder Cancers: A New Paradigm PURPOSE: Locally advanced (T3/T4) gallbladder cancers with large fixed portal nodes have a dismal prognosis. If undertaken, surgery entails extensive resections with high morbidity; therefore, in many centers, patients are offered palliative chemotherapy. In this prospective study, we used neoadjuvant concurrent chemoradiation with the intention of downstaging and facilitating R0 resection of these tumors. PATIENTS AND METHODS: Twenty-eight patients with locally advanced carcinoma gallbladder (stage III, having deep liver infiltrations and/or large portal nodes) underwent prior positron emission tomography/computed tomography to rule out metastatic disease. All were treated with concomitant chemoradiation using helical tomotherapy (dose of 57 Gy over 25 fractions to the gross tumor and 45 Gy over 25 fractions to the surrounding nodes) with injectable gemcitabine (300 mg/m(2)/week × 5 weeks). RESULTS: Of the 28 patients, 25 (89 %) successfully completed planned chemoradiation and 20 (71 %) achieved partial or complete radiologic response. Eighteen (64 %) patients were surgically explored, of whom 14 (56 %) achieved R0 resection. At the median follow-up of 37 months for the surviving patients, the median overall survival (OS) was 20 months for all patients. Only one patient recurred in the common bile duct postsurgery, whereas six patients had distant metastasis. The 5-year OS was 24 % for all patients and 47 % for patients with R0 resection. Biliary leak was seen in 6 (43 %) patients, of whom two required interventions. CONCLUSION: Locally advanced unresectable cancers may benefit from neoadjuvant chemoradiation to facilitate a curative resection with a good survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"predictors long term survival pancreaticoduodenectomy peri ampullary adenocarcinoma retrospective study 5 year survivors background pancreaticoduodenectomy pd standard curative treatment periampullary tumors aim study report incidence predictors long term survival 5 years pd methods study included patients underwent pd pathologically proven periampullary adenocarcinomas patients divided 2 groups group patients survived less 5 years group ii patients survived 5 years results 47 20 6 long term survivors 5 years among 228 patients underwent pd periampullary adenocarcinoma patients ampullary adenocarcinoma represented 31 66 0 long term survivors primary analysis showed favourable factors long term survival include age 60 years old serum cea 5 ng ml serum ca 19 9 37 u ml non cirrhotic liver tumor size 2 cm site primary tumor postoperative pancreatic fistula r0 resection postoperative chemotherapy recurrence multivariate analysis demonstrated ca 19 9 37 u ml 95 ci 1 712 1 248 2 348 p 0 001 smaller tumor size 95 ci 1 335 1 032 1 726 p 0 028 ro resection 95 ci 3 098 2 095 4 582 p 0 001 independent factors survival 5 years prognosis best ampullary adenocarcinoma median survival 54 months 5 year survival rate 39 0 poorest pancreatic head adenocarcinoma median survival 27 months 5 year survival rate 7 conclusions majority long term survivors pd periampullary adenocarcinoma patients ampullary tumor ca 19 9 37 u ml smaller tumor size r0 resection found independent factors long term survival 5 years stn","probabilities":0.9799733,"Title":"Predictors Of Long-Term Survival After Pancreaticoduodenectomy For Peri-Ampullary Adenocarcinoma: A Retrospective Study Of 5-Year Survivors","Abstract":"Background: Pancreaticoduodenectomy (PD) is the standard curative treatment for periampullary tumors. The aim of this study is to report the incidence and predictors of long-term survival (≥ 5 years) after PD. \r\n\r\n Methods: This study included patients who underwent PD for pathologically proven periampullary adenocarcinomas. Patients were divided into 2 groups: group (I) patients who survived less than 5 years and group (II) patients who survived ≥ 5 years. \r\n\r\n Results: There were 47 (20.6%) long-term survivors (≥ 5 years) among 228 patients underwent PD for periampullary adenocarcinoma. Patients with ampullary adenocarcinoma represented 31 (66.0%) of the long-term survivors. Primary analysis showed that favourable factors for long-term survival include age < 60 years old, serum CEA < 5 ng/mL, serum CA 19-9 < 37 U/mL, non-cirrhotic liver, tumor size < 2 cm, site of primary tumor, postoperative pancreatic fistula, R0 resection, postoperative chemotherapy, and no recurrence. Multivariate analysis demonstrated that CA 19-9 < 37 U/mL [OR (95% CI) = 1.712 (1.248-2.348), P = 0.001], smaller tumor size [OR (95% CI )= 1.335 (1.032-1.726), P = 0.028] and Ro resection [OR (95% CI) = 3.098 (2.095-4.582), P < 0.001] were independent factors for survival ≥ 5 years. The prognosis was best for ampullary adenocarcinoma, for which the median survival was 54 months and 5-year survival rate was 39.0%, and the poorest was pancreatic head adenocarcinoma, for which the median survival was 27 months and 5-year survival rate was 7%. \r\n\r\n Conclusions: The majority of long-term survivors after PD for periampullary adenocarcinoma are patients with ampullary tumor. CA 19-9 < 37 U/mL, smaller tumor size, and R0 resection were found to be independent factors for long-term survival ≥ 5 years.","Source":"STN","category":"HUMAN","training_data":"Predictors Of Long-Term Survival After Pancreaticoduodenectomy For Peri-Ampullary Adenocarcinoma: A Retrospective Study Of 5-Year Survivors Background: Pancreaticoduodenectomy (PD) is the standard curative treatment for periampullary tumors. The aim of this study is to report the incidence and predictors of long-term survival (≥ 5 years) after PD. \r\n\r\n Methods: This study included patients who underwent PD for pathologically proven periampullary adenocarcinomas. Patients were divided into 2 groups: group (I) patients who survived less than 5 years and group (II) patients who survived ≥ 5 years. \r\n\r\n Results: There were 47 (20.6%) long-term survivors (≥ 5 years) among 228 patients underwent PD for periampullary adenocarcinoma. Patients with ampullary adenocarcinoma represented 31 (66.0%) of the long-term survivors. Primary analysis showed that favourable factors for long-term survival include age < 60 years old, serum CEA < 5 ng/mL, serum CA 19-9 < 37 U/mL, non-cirrhotic liver, tumor size < 2 cm, site of primary tumor, postoperative pancreatic fistula, R0 resection, postoperative chemotherapy, and no recurrence. Multivariate analysis demonstrated that CA 19-9 < 37 U/mL [OR (95% CI) = 1.712 (1.248-2.348), P = 0.001], smaller tumor size [OR (95% CI )= 1.335 (1.032-1.726), P = 0.028] and Ro resection [OR (95% CI) = 3.098 (2.095-4.582), P < 0.001] were independent factors for survival ≥ 5 years. The prognosis was best for ampullary adenocarcinoma, for which the median survival was 54 months and 5-year survival rate was 39.0%, and the poorest was pancreatic head adenocarcinoma, for which the median survival was 27 months and 5-year survival rate was 7%. \r\n\r\n Conclusions: The majority of long-term survivors after PD for periampullary adenocarcinoma are patients with ampullary tumor. CA 19-9 < 37 U/mL, smaller tumor size, and R0 resection were found to be independent factors for long-term survival ≥ 5 years. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic potential carcinogenesis long non coding rna tug1 human cholangiocarcinoma cholangiocarcinoma cca fatal disease increasing worldwide incidence characterized poor prognosis due poor response conventional chemotherapy radiotherapy long non coding rnas lncrnas play key roles multiple human cancers including cca cancer progression related lncrna taurine regulated gene 1 tug1 reported involved human carcinomas however impact tug1 cca unclear aim study explore expression pattern tug1 evaluate clinical significance well prognostic potential cca addition functional roles tug1 including cell proliferation apoptosis migration invasion epithelial mesenchymal transition emt evaluated tug1 silencing data demonstrated regulation tug1 cca tissues cell lines moreover overexpression tug1 linked tumor size p 0 005 tnm stage p 0 013 postoperative recurrence p 0 036 overall survival p 0 010 cca patients furthermore regulation tug1 following rna silencing reduced cell growth increased apoptosis cca cells additionally tug1 suppression inhibited metastasis potential vitro reversing emt overall results suggest tug1 may rational cca related prognostic factor therapeutic target stn","probabilities":0.54545456,"Title":"The Prognostic Potential And Carcinogenesis Of Long Non-Coding Rna Tug1 In Human Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a fatal disease with increasing worldwide incidence and is characterized by poor prognosis due to its poor response to conventional chemotherapy or radiotherapy. Long non-coding RNAs (lncRNAs) play key roles in multiple human cancers, including CCA. Cancer progression related lncRNA taurine-up-regulated gene 1 (TUG1) was reported to be involved in human carcinomas. However, the impact of TUG1 in CCA is unclear. The aim of this study was to explore the expression pattern of TUG1 and evaluate its clinical significance as well as prognostic potential in CCA. In addition, the functional roles of TUG1 including cell proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT), were evaluated after TUG1 silencing. Our data demonstrated up-regulation of TUG1 in both CCA tissues and cell lines. Moreover, overexpression of TUG1 is linked to tumor size (p=0.005), TNM stage (p=0.013), postoperative recurrence (p=0.036) and overall survival (p=0.010) of CCA patients. Furthermore, down-regulation of TUG1 following RNA silencing reduced cell growth and increased apoptosis in CCA cells. Additionally, TUG1 suppression inhibited metastasis potential in vitro by reversing EMT. Overall, our results suggest that TUG1 may be a rational CCA-related prognostic factor and therapeutic target.","Source":"STN","category":"ANIMAL","training_data":"The Prognostic Potential And Carcinogenesis Of Long Non-Coding Rna Tug1 In Human Cholangiocarcinoma Cholangiocarcinoma (CCA) is a fatal disease with increasing worldwide incidence and is characterized by poor prognosis due to its poor response to conventional chemotherapy or radiotherapy. Long non-coding RNAs (lncRNAs) play key roles in multiple human cancers, including CCA. Cancer progression related lncRNA taurine-up-regulated gene 1 (TUG1) was reported to be involved in human carcinomas. However, the impact of TUG1 in CCA is unclear. The aim of this study was to explore the expression pattern of TUG1 and evaluate its clinical significance as well as prognostic potential in CCA. In addition, the functional roles of TUG1 including cell proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT), were evaluated after TUG1 silencing. Our data demonstrated up-regulation of TUG1 in both CCA tissues and cell lines. Moreover, overexpression of TUG1 is linked to tumor size (p=0.005), TNM stage (p=0.013), postoperative recurrence (p=0.036) and overall survival (p=0.010) of CCA patients. Furthermore, down-regulation of TUG1 following RNA silencing reduced cell growth and increased apoptosis in CCA cells. Additionally, TUG1 suppression inhibited metastasis potential in vitro by reversing EMT. Overall, our results suggest that TUG1 may be a rational CCA-related prognostic factor and therapeutic target. STN","prediction_labels":"HUMAN"},{"cleaned":"clinical outcomes toxicity using stereotactic body radiotherapy sbrt advanced cholangiocarcinoma background report single institutional clinical outcomes toxicity sbrt cholangiocarcinoma methods march 2009 july 2011 10 patients 12 unresectable primary n 6 recurrent n 6 cholangiocarcinoma lesions underwent abdominal sbrt sites treated included liver n 10 abdominal lymph nodes n 1 adrenal gland n 1 sbrt delivered three n 2 five n 10 consecutive daily fractions one week median prescription dose 55 gy range 45 60 treatment response graded recist v 1 1 toxicities scored ctcae v 4 0 data analyzed using kaplan meier method determine rates local control lc freedom distant progression ffdm overall survival os results median follow 14 months range 2 26 months lc defined freedom progression within sbrt field 100 four patients treated intrahepatic sites experienced progression elsewhere liver estimates ffdm 6 12 months 73 31 respectively sites disease relapse included liver n 3 liver lymph nodes n 1 liver lungs n 1 lymph nodes n 1 mesentery n 1 os estimates cohort 6 12 months 83 73 respectively common grade 2 early toxicities grade 2 nausea vomiting n 5 gastrointestinal pain n 2 late 2 toxicities included grade 2 gastrointestinal pain n 3 grade 3 biliary stenosis n 1 grade 5 liver failure n 1 conclusions sbrt shows promise effective local therapy properly selected patients cholangiocarcinoma follow needed better quantify risk late complications associated sbrt pubmed","probabilities":0.9799733,"Title":"Clinical outcomes and toxicity using stereotactic body radiotherapy (SBRT) for advanced cholangiocarcinoma","Abstract":"BACKGROUND: To report single-institutional clinical outcomes and toxicity with SBRT for cholangiocarcinoma. METHODS: From March 2009 to July 2011, 10 patients with 12 unresectable primary (n = 6) or recurrent (n = 6) cholangiocarcinoma lesions underwent abdominal SBRT. Sites treated included liver (n = 10), abdominal lymph nodes (n = 1), and adrenal gland (n = 1). SBRT was delivered in three (n = 2) or five (n = 10) consecutive daily fractions over one week. The median prescription dose was 55 Gy (range, 45-60). Treatment response was graded by RECIST v.1.1, and toxicities were scored by CTCAE v.4.0. Data was analyzed using the Kaplan-Meier method to determine rates of local control (LC), freedom from distant progression (FFDM) and overall survival (OS). RESULTS: The median follow-up was 14 months (range, 2-26 months). LC, defined as freedom from progression within the SBRT field, was 100%, but four patients treated to intrahepatic sites experienced progression elsewhere in the liver. Estimates for FFDM at 6 and 12 months were 73% and 31%, respectively. Sites of disease relapse included liver (n = 3), liver and lymph nodes (n = 1), liver and lungs (n = 1), lymph nodes (n = 1), and mesentery (n = 1). OS estimates for the cohort at 6 and 12 months were 83% and 73%, respectively. The most common Grade ≥ 2 early toxicities were Grade 2 nausea and vomiting (n = 5) and gastrointestinal pain (n = 2). Late ≥ 2 toxicities included Grade 2 gastrointestinal pain (n = 3), Grade 3 biliary stenosis (n = 1), and Grade 5 liver failure (n = 1). CONCLUSIONS: SBRT shows promise as an effective local therapy for properly-selected patients with cholangiocarcinoma. Further follow-up is needed to better quantify the risk of late complications associated with SBRT.","Source":"PubMed","category":"HUMAN","training_data":"Clinical outcomes and toxicity using stereotactic body radiotherapy (SBRT) for advanced cholangiocarcinoma BACKGROUND: To report single-institutional clinical outcomes and toxicity with SBRT for cholangiocarcinoma. METHODS: From March 2009 to July 2011, 10 patients with 12 unresectable primary (n = 6) or recurrent (n = 6) cholangiocarcinoma lesions underwent abdominal SBRT. Sites treated included liver (n = 10), abdominal lymph nodes (n = 1), and adrenal gland (n = 1). SBRT was delivered in three (n = 2) or five (n = 10) consecutive daily fractions over one week. The median prescription dose was 55 Gy (range, 45-60). Treatment response was graded by RECIST v.1.1, and toxicities were scored by CTCAE v.4.0. Data was analyzed using the Kaplan-Meier method to determine rates of local control (LC), freedom from distant progression (FFDM) and overall survival (OS). RESULTS: The median follow-up was 14 months (range, 2-26 months). LC, defined as freedom from progression within the SBRT field, was 100%, but four patients treated to intrahepatic sites experienced progression elsewhere in the liver. Estimates for FFDM at 6 and 12 months were 73% and 31%, respectively. Sites of disease relapse included liver (n = 3), liver and lymph nodes (n = 1), liver and lungs (n = 1), lymph nodes (n = 1), and mesentery (n = 1). OS estimates for the cohort at 6 and 12 months were 83% and 73%, respectively. The most common Grade ≥ 2 early toxicities were Grade 2 nausea and vomiting (n = 5) and gastrointestinal pain (n = 2). Late ≥ 2 toxicities included Grade 2 gastrointestinal pain (n = 3), Grade 3 biliary stenosis (n = 1), and Grade 5 liver failure (n = 1). CONCLUSIONS: SBRT shows promise as an effective local therapy for properly-selected patients with cholangiocarcinoma. Further follow-up is needed to better quantify the risk of late complications associated with SBRT. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incretin based drugs risk cholangiocarcinoma among patients type 2 diabetes population based cohort study objective determine whether use dipeptidyl peptidase 4 dpp 4 inhibitors glucagon like peptide 1 glp 1 receptor agonists associated increased risk cholangiocarcinoma adults type 2 diabetes design population based cohort study setting general practices contributing data uk clinical practice research datalink participants 154 162 adults newly treated antidiabetic drugs 1 january 2007 31 march 2017 followed 31 march 2018 main outcome measures use dpp 4 inhibitors glp 1 receptor agonists modelled time varying variable compared use second third line antidiabetic drugs exposures lagged one year account cancer latency minimise reverse causality cox proportional hazards models used estimate hazard ratios 95 confidence intervals incident cholangiocarcinoma associated use dpp 4 inhibitors glp 1 receptor agonists separately post hoc pharmacovigilance analysis conducted using world health organization global individual case safety report database vigibase estimate reporting odds ratios cholangiocarcinoma results 614 274 person years follow 105 incident cholangiocarcinoma events occurred rate 17 1 per 100 000 person years use dpp 4 inhibitors associated 77 increased hazard cholangiocarcinoma hazard ratio 1 77 95 confidence interval 1 04 3 01 use glp 1 receptor agonists associated increased hazard wide confidence interval hazard ratio 1 97 0 83 4 66 pharmacovigilance analysis use dpp 4 inhibitors glp 1 receptor agonists associated increased reporting odds ratios cholangiocarcinoma compared use sulfonylureas thiazolidinediones 1 63 1 00 2 66 4 73 2 95 7 58 respectively conclusion compared use second third line antidiabetic drugs use dpp 4 inhibitors possibly glp 1 receptor agonists might associated increased risk cholangiocarcinoma adults type 2 diabetes pubmed","probabilities":0.9799733,"Title":"Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study","Abstract":"OBJECTIVE: To determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. DESIGN: Population based cohort study. SETTING: General practices contributing data to the UK Clinical Practice Research Datalink. PARTICIPANTS: 154 162 adults newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2017, followed until 31 March 2018. MAIN OUTCOME MEASURES: Use of DPP-4 inhibitors and GLP-1 receptor agonists was modelled as a time varying variable and compared with use of other second or third line antidiabetic drugs. All exposures were lagged by one year to account for cancer latency and to minimise reverse causality. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of incident cholangiocarcinoma associated with use of DPP-4 inhibitors and GLP-1 receptor agonists, separately. A post hoc pharmacovigilance analysis was conducted using the World Health Organization's global individual case safety report database, VigiBase, to estimate reporting odds ratios of cholangiocarcinoma. RESULTS: During 614 274 person years of follow-up, 105 incident cholangiocarcinoma events occurred (rate 17.1 per 100 000 person years). Use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma (hazard ratio 1.77, 95% confidence interval 1.04 to 3.01). Use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval (hazard ratio 1.97, 0.83 to 4.66). In the pharmacovigilance analysis, the use of DPP-4 inhibitors and GLP-1 receptor agonists were both associated with increased reporting odds ratios for cholangiocarcinoma, compared with use of sulfonylureas or thiazolidinediones (1.63, 1.00 to 2.66, 4.73, 2.95 to 7.58, respectively). CONCLUSION: Compared with use of other second or third line antidiabetic drugs, use of DPP-4 inhibitors, and possibly GLP-1 receptor agonists, might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes.","Source":"PubMed","category":"HUMAN","training_data":"Incretin based drugs and risk of cholangiocarcinoma among patients with type 2 diabetes: population based cohort study OBJECTIVE: To determine whether use of dipeptidyl peptidase-4 (DPP-4) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists are associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. DESIGN: Population based cohort study. SETTING: General practices contributing data to the UK Clinical Practice Research Datalink. PARTICIPANTS: 154 162 adults newly treated with antidiabetic drugs between 1 January 2007 and 31 March 2017, followed until 31 March 2018. MAIN OUTCOME MEASURES: Use of DPP-4 inhibitors and GLP-1 receptor agonists was modelled as a time varying variable and compared with use of other second or third line antidiabetic drugs. All exposures were lagged by one year to account for cancer latency and to minimise reverse causality. Cox proportional hazards models were used to estimate hazard ratios and 95% confidence intervals of incident cholangiocarcinoma associated with use of DPP-4 inhibitors and GLP-1 receptor agonists, separately. A post hoc pharmacovigilance analysis was conducted using the World Health Organization's global individual case safety report database, VigiBase, to estimate reporting odds ratios of cholangiocarcinoma. RESULTS: During 614 274 person years of follow-up, 105 incident cholangiocarcinoma events occurred (rate 17.1 per 100 000 person years). Use of DPP-4 inhibitors was associated with a 77% increased hazard of cholangiocarcinoma (hazard ratio 1.77, 95% confidence interval 1.04 to 3.01). Use of GLP-1 receptor agonists was associated with an increased hazard with a wide confidence interval (hazard ratio 1.97, 0.83 to 4.66). In the pharmacovigilance analysis, the use of DPP-4 inhibitors and GLP-1 receptor agonists were both associated with increased reporting odds ratios for cholangiocarcinoma, compared with use of sulfonylureas or thiazolidinediones (1.63, 1.00 to 2.66, 4.73, 2.95 to 7.58, respectively). CONCLUSION: Compared with use of other second or third line antidiabetic drugs, use of DPP-4 inhibitors, and possibly GLP-1 receptor agonists, might be associated with an increased risk of cholangiocarcinoma in adults with type 2 diabetes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"serum vascular endothelial growth factor c levels predict lymph node metastasis prognosis patients gallbladder cancer lymph node metastasis primary site metastasis patients gallbladder cancer gbc vascular endothelial growth factor c vegf c implicated control lymphangiogenesis lymph node metastasis various malignant tumors however function circulating vegf c unclear often difficult evaluate lymph node metastasis provide prognosis gbc present study elisa used measure preoperative serum vegf c svegf c levels 51 patients gbc 15 patients chronic cholecystitis 10 healthy volunteers results revealed significantly increased svegf c level patients gbc compared healthy donors however statistically significant difference identified patients gbc chronic cholecystitis svegf c levels associated lymph node metastasis gbc presented positive correlation vegf c expression lymphatic vessel density lvd patients gbc mean survival time high svegf c significantly reduced compared low svegf c similar result also observed vegf c expression lvd summary svegf c levels may predict lymph node metastasis prognosis patients gbc stn","probabilities":0.9799733,"Title":"Serum Vascular Endothelial Growth Factor-C Levels Predict Lymph Node Metastasis And Prognosis Of Patients With Gallbladder Cancer","Abstract":"Lymph node metastasis is the primary site of metastasis for patients with gallbladder cancer (GBC). Vascular endothelial growth factor-C (VEGF-C) has been implicated in the control of lymphangiogenesis and lymph node metastasis in various malignant tumors. However, the function of circulating VEGF-C is unclear and it is often difficult to evaluate lymph node metastasis and provide a prognosis for GBC. In the present study, ELISA was used to measure the preoperative serum VEGF-C (sVEGF-C) levels of 51 patients with GBC, 15 patients with chronic cholecystitis and 10 healthy volunteers. The results revealed a significantly increased sVEGF-C level in patients with GBC compared with the healthy donors, however no statistically significant difference was identified between patients with GBC and chronic cholecystitis. sVEGF-C levels were associated with lymph node metastasis in GBC and presented a positive correlation with VEGF-C expression and lymphatic vessel density (LVD) in patients with GBC. The mean survival time with high sVEGF-C was significantly reduced compared with low sVEGF-C. A similar result was also observed for VEGF-C expression and LVD. In summary, sVEGF-C levels may predict lymph node metastasis and the prognosis of patients with GBC.","Source":"STN","category":"HUMAN","training_data":"Serum Vascular Endothelial Growth Factor-C Levels Predict Lymph Node Metastasis And Prognosis Of Patients With Gallbladder Cancer Lymph node metastasis is the primary site of metastasis for patients with gallbladder cancer (GBC). Vascular endothelial growth factor-C (VEGF-C) has been implicated in the control of lymphangiogenesis and lymph node metastasis in various malignant tumors. However, the function of circulating VEGF-C is unclear and it is often difficult to evaluate lymph node metastasis and provide a prognosis for GBC. In the present study, ELISA was used to measure the preoperative serum VEGF-C (sVEGF-C) levels of 51 patients with GBC, 15 patients with chronic cholecystitis and 10 healthy volunteers. The results revealed a significantly increased sVEGF-C level in patients with GBC compared with the healthy donors, however no statistically significant difference was identified between patients with GBC and chronic cholecystitis. sVEGF-C levels were associated with lymph node metastasis in GBC and presented a positive correlation with VEGF-C expression and lymphatic vessel density (LVD) in patients with GBC. The mean survival time with high sVEGF-C was significantly reduced compared with low sVEGF-C. A similar result was also observed for VEGF-C expression and LVD. In summary, sVEGF-C levels may predict lymph node metastasis and the prognosis of patients with GBC. STN","prediction_labels":"HUMAN"},{"cleaned":"circulating tumor cells associated poor overall survival patients cholangiocarcinoma circulating tumor cells ctcs blood associated poor survival patients breast prostate colon cancer hypothesized ctcs associated poor survival patients cholangiocarcinoma cca eighty eight patients cca prospectively enrolled mayo clinic rochester june 2010 september 2014 cellsearch system veridex used detection ctcs peripheral blood associations ctc patient tumor characteristics survival examined using cox proportional hazards model fifteen patients 17 positive ctc 2 8 patients 9 ctc 5 ctcs associated tumor extent ctc 2 hazard ratio hr 2 5 95 confidence interval ci 1 1 5 4 p 0 02 ctc 5 hr 4 1 95 ci 1 4 10 8 p 0 01 independent predictors survival subgroup analyses ctc 2 hr 8 2 95 ci 1 8 57 5 p 0 01 ctc 5 hr 7 7 95 ci 1 4 42 9 p 0 02 associated shorter survival among patients metastasis trend toward association ctc 5 shorter survival patients nonmetastatic cca hr 4 3 95 ci 1 0 13 8 p 0 06 ctc 2 hr 10 5 95 ci 2 2 40 1 p 0 01 ctc 5 hr 10 2 95 ci 1 5 42 3 p 0 02 associated shorter survival among patients perihilar distal cca ctc 5 associated shorter survival patients intrahepatic cca hr 4 2 95 ci 1 1 14 1 p 0 04 conclusion ctcs associated aggressive tumor characteristics independently associated survival patients cca assessment ctcs may useful identifying cca patients risk early mortality pubmed","probabilities":0.9799733,"Title":"Circulating tumor cells are associated with poor overall survival in patients with cholangiocarcinoma","Abstract":"Circulating tumor cells (CTCs) in blood are associated with poor survival of patients with breast, prostate, or colon cancer. We hypothesized that CTCs are associated with poor survival of patients with cholangiocarcinoma (CCA). Eighty-eight patients with CCA were prospectively enrolled at Mayo Clinic Rochester between June 2010 and September 2014. The CellSearch system by Veridex was used for detection of CTCs in peripheral blood. Associations between CTC, patient and tumor characteristics, and survival were examined using the Cox's proportional hazards model. Fifteen patients (17%) were positive for CTC ≥2 and 8 patients (9%) for CTC ≥5. CTCs were associated with tumor extent. CTC ≥2 (hazard ratio [HR]: 2.5; 95% confidence interval [CI]: 1.1-5.4; P = 0.02) and CTC ≥5 (HR, 4.1; 95% CI: 1.4-10.8; P = 0.01) were both independent predictors of survival. In subgroup analyses, CTC ≥2 (HR, 8.2; 95% CI: 1.8-57.5; P < 0.01) and CTC ≥5 (HR, 7.7; 95% CI: 1.4-42.9; P = 0.02) were both associated with shorter survival among patients with metastasis. There was a trend toward association of CTC ≥5 with shorter survival in patients with nonmetastatic CCA (HR, 4.3; 95% CI: 1.0-13.8; P = 0.06). CTC ≥2 (HR, 10.5; 95% CI: 2.2-40.1; P < 0.01) and CTC ≥5 (HR, 10.2; 95% CI: 1.5-42.3; P = 0.02) were both associated with shorter survival among patients with perihilar/distal CCA. CTC ≥5 was associated with shorter survival of patients with intrahepatic CCA (HR, 4.2; 95% CI: 1.1-14.1; P = 0.04). CONCLUSION: CTCs were associated with more-aggressive tumor characteristics and independently associated with survival in patients with CCA. Assessment of CTCs may be useful for identifying CCA patients at risk of early mortality.","Source":"PubMed","category":"HUMAN","training_data":"Circulating tumor cells are associated with poor overall survival in patients with cholangiocarcinoma Circulating tumor cells (CTCs) in blood are associated with poor survival of patients with breast, prostate, or colon cancer. We hypothesized that CTCs are associated with poor survival of patients with cholangiocarcinoma (CCA). Eighty-eight patients with CCA were prospectively enrolled at Mayo Clinic Rochester between June 2010 and September 2014. The CellSearch system by Veridex was used for detection of CTCs in peripheral blood. Associations between CTC, patient and tumor characteristics, and survival were examined using the Cox's proportional hazards model. Fifteen patients (17%) were positive for CTC ≥2 and 8 patients (9%) for CTC ≥5. CTCs were associated with tumor extent. CTC ≥2 (hazard ratio [HR]: 2.5; 95% confidence interval [CI]: 1.1-5.4; P = 0.02) and CTC ≥5 (HR, 4.1; 95% CI: 1.4-10.8; P = 0.01) were both independent predictors of survival. In subgroup analyses, CTC ≥2 (HR, 8.2; 95% CI: 1.8-57.5; P < 0.01) and CTC ≥5 (HR, 7.7; 95% CI: 1.4-42.9; P = 0.02) were both associated with shorter survival among patients with metastasis. There was a trend toward association of CTC ≥5 with shorter survival in patients with nonmetastatic CCA (HR, 4.3; 95% CI: 1.0-13.8; P = 0.06). CTC ≥2 (HR, 10.5; 95% CI: 2.2-40.1; P < 0.01) and CTC ≥5 (HR, 10.2; 95% CI: 1.5-42.3; P = 0.02) were both associated with shorter survival among patients with perihilar/distal CCA. CTC ≥5 was associated with shorter survival of patients with intrahepatic CCA (HR, 4.2; 95% CI: 1.1-14.1; P = 0.04). CONCLUSION: CTCs were associated with more-aggressive tumor characteristics and independently associated with survival in patients with CCA. Assessment of CTCs may be useful for identifying CCA patients at risk of early mortality. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence survival mortality trends hepatic intrahepatic bile duct cancer united states surveillance epidemiology end results seer database study 1975 2016 background using seer data studied trends patient characteristics age gender race incidence survival liver intrahepatic bile duct cancer us methods patients diagnosed primary hepatic intrahepatic biliary duct cancer 1975 2016 identi ed seer registries incorporated seer 9 21 registries determine incidence ethnicity disease characteristics study survival trends results hepatocellular carcinoma hcc cholangiocarcinoma common subtypes 70 0 vs 24 subtypes include carcinomas 4 hepatoblastoma 1 sarcoma 1 higher proportion cases diagnosed localized 44 compared regional 27 distant 18 disease males m higher incidence rates females f 13 6 vs 4 7 100000 age ethnicity observed incidence rate increasing average 2 1 year y last 10 years observed highest incidence rates races age range 55 64 years whites w 80 84 years blacks b 60 64 years incidence rate highest hispanics asian paci c islanders 13 6 100000 compared american indian alaska natives b w 13 vs 10 8 vs 8 100000 mortality rates increased average 2 4 y 2007 16 5 3 6 6 100000 5 y survival rates 2009 2015 similar m f 20 vs 19 higher patients 65y compared 65 y older 22 vs 14 comparison 5 y survival rates strati cation aforementioned age categories shows w 22 vs 12 b 16 vs 13 wm 20 vs 14 wf 27 vs 13 bm 14 vs 13 bf 21 vs 13 indicating overall poor survival bm bf age 65 5 y survival rates worse distant disease compared localized disease 2 vs 11 vs 33 conclusion epidemiological trends show increasing incidence rate hepatic intrahepatic bile duct malignancies overall 5 y survival rates improved black males advanced age distant disease worse outcomes since bf 65y age better outcome bm similar age group postulate disease pathogenesis varies gender races without considering socioeconomic factorss google scholar","probabilities":0.9799733,"Title":"Incidence Survival And Mortality Trends For Hepatic And Intrahepatic Bile Duct Cancer In The United States: A Surveillance Epidemiology And End Results (Seer) Database Study 1975-2016","Abstract":"Background: Using SEER data, we studied trends in patient characteristics such as age, gender and race and the incidence and survival in liver and intrahepatic bile duct cancer in the US. Methods: Patients diagnosed with primary hepatic and intrahepatic biliary duct cancer between 1975-2016 were identied in SEER registries. We incorporated SEER-9 and 21 registries to determine incidence, ethnicity and disease characteristics and to study survival trends. Results: Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the most common subtypes (70.0 vs 24%); other subtypes include other carcinomas (4%), hepatoblastoma (1%) and sarcoma (1%). Higher proportion of cases were diagnosed with localized (44%) compared to regional (27%) or distant (18%) disease. Males (M) had higher incidence rates than females (F) (13.6 vs 4.7/100000) for any age and ethnicity. Observed incidence rate has been increasing on average 2.1%/year(y) over last 10 years. We observed highest incidence rates: for all races between age range 55-64 years; Whites (W) between 80-84 years; Blacks (B) 60-64 years. Incidence rate is highest for Hispanics and Asian/Pacic Islanders (13.6/100000 each) compared to American Indian/Alaska Natives, B and W (13 vs 10.8 vs 8/100000). Mortality rates increased an average of 2.4% /y between 2007-16 from 5.3 to 6.6/100000. 5-y survival rates between 2009-2015 were similar for M and F (20% vs 19%) and higher for patients < 65y compared to 65 y and older (22% vs 14%). Comparison of the 5-y survival rates after stratication by aforementioned age-categories shows: W (22% vs 12%); B (16% vs 13%); WM (20% vs 14%) and WF (27% vs 13%); BM (14% vs 13%) and BF (21% vs 13%), indicating overall poor survival for BM and BF >age 65. 5-y survival rates are worse for distant disease compared to localized disease (2% vs 11% vs 33%). Conclusion: Epidemiological trends show increasing incidence rate for hepatic/intrahepatic bile duct malignancies. Overall 5-y survival rates have improved. Black males, advanced age and distant disease have worse outcomes. Since BF <65y age have better outcome than BM in similar age group, we postulate that the disease pathogenesis varies by gender and races without considering the socioeconomic factorss","Source":"Google Scholar","category":"HUMAN","training_data":"Incidence Survival And Mortality Trends For Hepatic And Intrahepatic Bile Duct Cancer In The United States: A Surveillance Epidemiology And End Results (Seer) Database Study 1975-2016 Background: Using SEER data, we studied trends in patient characteristics such as age, gender and race and the incidence and survival in liver and intrahepatic bile duct cancer in the US. Methods: Patients diagnosed with primary hepatic and intrahepatic biliary duct cancer between 1975-2016 were identied in SEER registries. We incorporated SEER-9 and 21 registries to determine incidence, ethnicity and disease characteristics and to study survival trends. Results: Hepatocellular carcinoma (HCC) and cholangiocarcinoma are the most common subtypes (70.0 vs 24%); other subtypes include other carcinomas (4%), hepatoblastoma (1%) and sarcoma (1%). Higher proportion of cases were diagnosed with localized (44%) compared to regional (27%) or distant (18%) disease. Males (M) had higher incidence rates than females (F) (13.6 vs 4.7/100000) for any age and ethnicity. Observed incidence rate has been increasing on average 2.1%/year(y) over last 10 years. We observed highest incidence rates: for all races between age range 55-64 years; Whites (W) between 80-84 years; Blacks (B) 60-64 years. Incidence rate is highest for Hispanics and Asian/Pacic Islanders (13.6/100000 each) compared to American Indian/Alaska Natives, B and W (13 vs 10.8 vs 8/100000). Mortality rates increased an average of 2.4% /y between 2007-16 from 5.3 to 6.6/100000. 5-y survival rates between 2009-2015 were similar for M and F (20% vs 19%) and higher for patients < 65y compared to 65 y and older (22% vs 14%). Comparison of the 5-y survival rates after stratication by aforementioned age-categories shows: W (22% vs 12%); B (16% vs 13%); WM (20% vs 14%) and WF (27% vs 13%); BM (14% vs 13%) and BF (21% vs 13%), indicating overall poor survival for BM and BF >age 65. 5-y survival rates are worse for distant disease compared to localized disease (2% vs 11% vs 33%). Conclusion: Epidemiological trends show increasing incidence rate for hepatic/intrahepatic bile duct malignancies. Overall 5-y survival rates have improved. Black males, advanced age and distant disease have worse outcomes. Since BF <65y age have better outcome than BM in similar age group, we postulate that the disease pathogenesis varies by gender and races without considering the socioeconomic factorss Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"induction survival pathways human cholangiocarcinoma cells following photodynamic therapy background photodynamic therapy pdt solid cancers comprises administration photosensitizer followed illumination photosensitizer replete tumor laser light induces state local oxidative stress culminating destruction tumor tissue microvasculature induction anti tumor immune response however tumor types including perihilar cholangiocarcinoma relatively refractory pdt may attributable activation survival pathways tumor cells following pdt e activator protein 1 ap 1 nuclear factor kappa light polypeptide gene enhancer b cells nf b hypoxia inducible factor 1 alpha hif 1 nuclear factor erythroid derived 2 like 2 nfe2l2 unfolded protein response mediated pathways methods assess activation survival pathways pdt human perihilar cholangiocarcinoma sk cha 1 cells subjected pdt zinc phthalocyanine znpc encapsulating liposomes following 30 minute incubation liposomes cells either left untreated treated low 50 mw high 500 mw laser power cumulative light dose 15 j cm 2 cells harvested 90 min post pdt whole genome expression analysis performed using illumina humanht 12 v4 expression beadchips data interpreted context survival pathways addition safety znpc encapsulating liposomes tested vitro vivo results pdt treated sk cha 1 cells exhibited activation hypoxia induced stress response via hif 1 initiation pro inflammatory response via nf b pdt low laser power particular caused extensive survival signaling evidenced significant upregulation hif 1 p 0 001 nf b related p 0 001 genes low power pdt less lethal sk cha 1 cells 90 min post pdt confirmed annexin v propidium iodide staining vitro toxicogenomics toxicological testing chicken embryos mice revealed znpc encapsulating liposomes non toxic conclusions pdt treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling may translate suboptimal therapeutic response possibly tumor recurrence findings encourage development photosensitizer delivery systems co encapsulated inhibitors survival pathways stn","probabilities":1.0,"Title":"Induction Of Survival Pathways In Human Cholangiocarcinoma Cells Following Photodynamic Therapy","Abstract":"Background: Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways). \r\n\r\n Methods: To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm(2)). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo. \r\n\r\n Results: PDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic. \r\n\r\n Conclusions: PDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways.","Source":"STN","category":"ANIMAL","training_data":"Induction Of Survival Pathways In Human Cholangiocarcinoma Cells Following Photodynamic Therapy Background: Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways). \r\n\r\n Methods: To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm(2)). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo. \r\n\r\n Results: PDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic. \r\n\r\n Conclusions: PDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways. STN","prediction_labels":"ANIMAL"},{"cleaned":"differences metabolic behavior intra extrahepatic cholangiocarcinomas 18 f fdg pet ct prognostic implication metabolic parameters tumor markers background purpose cholangiocarcinoma infrequent neoplasm barely studied 18 f fdg pet ct evaluated metabolic behavior cholangiocarcinoma pet ct according location intra extrahepatic analyzed relationship metabolic parameters primary tumor tumor markers ca19 9 cea determining prognostic significance methods retrospective study pet ct 60 patients untreated cholangiocarcinoma divided two groups according tumor location fdg uptake evaluated visually semiquantitatively suvmax tumor liver ratio tlr differences intra extrahepatic cholangiocarcinomas tested fdg uptake primary tumor presence regional distant disease per patient well regarding tumor marker levels correlation metabolic parameters tumor markers performed prognostic value factors determined univariate multivariate analyses results intrahepatic cholangiocarcinomas significantly fdg avid extrahepatic ones p 0 006 suvmax p 0 002 tlr differences neither groups considering capacity pet ct detect regional p 0 261 distant involvement p 0 876 regarding levels tumor markers p 0 160 ca19 9 p 0 708 cea metabolic parameters tumor markers showed weak positive correlation r 2 0 22 0 27 multivariate analysis advanced stage p 0 024 increased cea p 0 022 higher tlr p 0 003 significantly related shorter overall survival conclusions intra extrahepatic cholangiocarcinomas behave differently pet ct though differences groups exist capacity detect regional distant disease metabolic parameters levels tumor markers seem relate tumor burden impacting prognosis pubmed","probabilities":0.9799733,"Title":"Differences on metabolic behavior between intra and extrahepatic cholangiocarcinomas at (18)F-FDG-PET/CT: prognostic implication of metabolic parameters and tumor markers","Abstract":"BACKGROUND AND PURPOSE: Cholangiocarcinoma is an infrequent neoplasm barely studied with (18)F-FDG-PET/CT. We evaluated the metabolic behavior of cholangiocarcinoma in PET/CT according to its location (intra or extrahepatic) and analyzed the relationship between metabolic parameters of the primary tumor and tumor markers (CA19-9 and CEA), determining their prognostic significance. METHODS: Retrospective study of PET/CT of 60 patients with untreated cholangiocarcinoma, divided into two groups according to tumor location. FDG uptake was evaluated visually and semiquantitatively [SUVmax and tumor-to-liver ratio (TLR)], and differences between intra and extrahepatic cholangiocarcinomas were tested, both for FDG uptake in the primary tumor and for the presence of regional or distant disease (per-patient), as well as regarding tumor marker levels. A correlation between metabolic parameters and tumor markers was performed, and prognostic value of these factors was determined (univariate and multivariate analyses). RESULTS: Intrahepatic cholangiocarcinomas were significantly more FDG-avid than extrahepatic ones (p = 0.006 for SUVmax; p = 0.002 for TLR). There were differences neither between both groups considering the capacity of PET/CT to detect regional (p = 0.261) and distant involvement (p = 0.876), nor regarding the levels of tumor markers (p = 0.160 for CA19-9; p = 0.708 for CEA). Metabolic parameters and tumor markers showed a weak positive correlation (R(2) 0.22-0.27). At the multivariate analysis, advanced stage (p = 0.024), increased CEA (p = 0.022), and higher TLR (p = 0.003) were significantly related with shorter overall survival. CONCLUSIONS: Intra and extrahepatic cholangiocarcinomas behave differently on PET/CT, though no differences between both groups exist in its capacity to detect regional or distant disease. Metabolic parameters and levels of tumor markers seem to relate with tumor burden, impacting in prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Differences on metabolic behavior between intra and extrahepatic cholangiocarcinomas at (18)F-FDG-PET/CT: prognostic implication of metabolic parameters and tumor markers BACKGROUND AND PURPOSE: Cholangiocarcinoma is an infrequent neoplasm barely studied with (18)F-FDG-PET/CT. We evaluated the metabolic behavior of cholangiocarcinoma in PET/CT according to its location (intra or extrahepatic) and analyzed the relationship between metabolic parameters of the primary tumor and tumor markers (CA19-9 and CEA), determining their prognostic significance. METHODS: Retrospective study of PET/CT of 60 patients with untreated cholangiocarcinoma, divided into two groups according to tumor location. FDG uptake was evaluated visually and semiquantitatively [SUVmax and tumor-to-liver ratio (TLR)], and differences between intra and extrahepatic cholangiocarcinomas were tested, both for FDG uptake in the primary tumor and for the presence of regional or distant disease (per-patient), as well as regarding tumor marker levels. A correlation between metabolic parameters and tumor markers was performed, and prognostic value of these factors was determined (univariate and multivariate analyses). RESULTS: Intrahepatic cholangiocarcinomas were significantly more FDG-avid than extrahepatic ones (p = 0.006 for SUVmax; p = 0.002 for TLR). There were differences neither between both groups considering the capacity of PET/CT to detect regional (p = 0.261) and distant involvement (p = 0.876), nor regarding the levels of tumor markers (p = 0.160 for CA19-9; p = 0.708 for CEA). Metabolic parameters and tumor markers showed a weak positive correlation (R(2) 0.22-0.27). At the multivariate analysis, advanced stage (p = 0.024), increased CEA (p = 0.022), and higher TLR (p = 0.003) were significantly related with shorter overall survival. CONCLUSIONS: Intra and extrahepatic cholangiocarcinomas behave differently on PET/CT, though no differences between both groups exist in its capacity to detect regional or distant disease. Metabolic parameters and levels of tumor markers seem to relate with tumor burden, impacting in prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"reduced levels n methyl 2 pyridone 5 carboxamide lysophosphatidylcholine 16 0 serum patients intrahepatic cholangiocarcinoma correlation recurrence free survival searched metabolic biomarkers may predict prognosis patients intrahepatic cholangiocarcinoma ihcc end total 237 serum samples obtained ihcc patients n 87 healthy controls n 150 serum metabolites analyzed liquid chromatography tandem mass spectrometry lc ms ms two stratified algorithms used select metabolites levels predicted prognosis ihcc patients performed ms ms multiple reaction monitoring ms analyses identify quantify selected metabolites continuous biomarker levels dichotomized based cutoffs maximized group differences recurrence free survival rfs terms log rank test statistic rfs differences analyzed using log rank test survival curves drawn aid kaplan meier method six metabolites l glutamine lysophosphatidylcholine lpc 16 0 lpc 18 0 n methyl 2 pyridone 5 carboxamide 2py fibrinopeptide fpa uric acid identified candidate metabolic biomarkers predicting prognosis ihcc patients metabolites levels l glutamine uric acid lpc 16 0 lpc 18 0 significantly lower serum ihcc patients whereas levels 2py fpa significantly higher p 0 01 2py lpc 16 0 showed significantly better rfs low level high level 2py median rfs 15 16 months vs 5 90 months p 0 037 lpc 16 0 median rfs 15 62 months vs 9 83 months p 0 035 findings study suggest 2py lpc 16 0 identified metabolome based approaches may useful biomarkers ihcc patients stn","probabilities":0.9799733,"Title":"Reduced Levels Of N'-Methyl-2-Pyridone-5-Carboxamide And Lysophosphatidylcholine 16:0 In The Serum Of Patients With Intrahepatic Cholangiocarcinoma And The Correlation With Recurrence-Free Survival","Abstract":"We searched for metabolic biomarkers that may predict the prognosis of patients with intrahepatic cholangiocarcinoma (IHCC). To this end, a total of 237 serum samples were obtained from IHCC patients (n = 87) and healthy controls (n = 150), and serum metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two stratified algorithms were used to select the metabolites, the levels of which predicted the prognosis of IHCC patients. We performed MS/MS and multiple-reaction-monitoring MS analyses to identify and quantify the selected metabolites. Continuous biomarker levels were dichotomized based on cutoffs that maximized between-group differences in recurrence-free survival (RFS) in terms of the log-rank test statistic. These RFS differences were analyzed using the log-rank test, and survival curves were drawn with the aid of the Kaplan-Meier method. Six metabolites (l-glutamine, lysophosphatidylcholine [LPC] 16:0, LPC 18:0, N'-methyl-2-pyridone-5-carboxamide [2PY], fibrinopeptide A [FPA] and uric acid) were identified as candidate metabolic biomarkers for predicting the prognosis of IHCC patients. Of these metabolites, levels of l-glutamine, uric acid, LPC 16:0, and LPC 18:0 were significantly lower in the serum from IHCC patients, whereas levels of 2PY and FPA were significantly higher (p < 0.01). 2PY and LPC 16:0 showed significantly better RFS at low level than high level (2PY, median RFS: 15.16 months vs. 5.90 months, p = 0.037; LPC 16:0, median RFS: 15.62 months vs. 9.83 months, p = 0.035). The findings of this study suggest that 2PY and LPC 16:0 identified by metabolome-based approaches may be useful biomarkers for IHCC patients.","Source":"STN","category":"ANIMAL","training_data":"Reduced Levels Of N'-Methyl-2-Pyridone-5-Carboxamide And Lysophosphatidylcholine 16:0 In The Serum Of Patients With Intrahepatic Cholangiocarcinoma And The Correlation With Recurrence-Free Survival We searched for metabolic biomarkers that may predict the prognosis of patients with intrahepatic cholangiocarcinoma (IHCC). To this end, a total of 237 serum samples were obtained from IHCC patients (n = 87) and healthy controls (n = 150), and serum metabolites were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Two stratified algorithms were used to select the metabolites, the levels of which predicted the prognosis of IHCC patients. We performed MS/MS and multiple-reaction-monitoring MS analyses to identify and quantify the selected metabolites. Continuous biomarker levels were dichotomized based on cutoffs that maximized between-group differences in recurrence-free survival (RFS) in terms of the log-rank test statistic. These RFS differences were analyzed using the log-rank test, and survival curves were drawn with the aid of the Kaplan-Meier method. Six metabolites (l-glutamine, lysophosphatidylcholine [LPC] 16:0, LPC 18:0, N'-methyl-2-pyridone-5-carboxamide [2PY], fibrinopeptide A [FPA] and uric acid) were identified as candidate metabolic biomarkers for predicting the prognosis of IHCC patients. Of these metabolites, levels of l-glutamine, uric acid, LPC 16:0, and LPC 18:0 were significantly lower in the serum from IHCC patients, whereas levels of 2PY and FPA were significantly higher (p < 0.01). 2PY and LPC 16:0 showed significantly better RFS at low level than high level (2PY, median RFS: 15.16 months vs. 5.90 months, p = 0.037; LPC 16:0, median RFS: 15.62 months vs. 9.83 months, p = 0.035). The findings of this study suggest that 2PY and LPC 16:0 identified by metabolome-based approaches may be useful biomarkers for IHCC patients. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance neutrophil lymphocyte ratio carbohydrate antigen 19 9 patients gallbladder carcinoma neutrophil lymphocyte ratio nlr immune response related indicator associated poor prognosis various cancers carbohydrate antigen19 9 ca19 9 tumor associated antigen prognostic relevance gallbladder carcinoma gbc aimed analyze whether preoperative nlr serum ca19 9 associated outcomes gbc patients surgery curative intent january 2010 may 2015 90 resectable gbc patients underwent curative surgery institution included final diagnoses confirmed pathologic examination demographics clinical histopathology data analyzed cox regression proportional hazard model kaplan meier method used assess prognostic factors cutoff values 4 33 250 90 u ml defined high nlr high ca19 9 respectively univariate analyses showed tnm stage lymph node metastasis degree tumor differentiation margin status combined hepatectomy ca19 9 nlr pni associated overall survival p 05 according multivariable analysis nlr hazard ratio hr 3 840 95 confidence interval 95 ci 2 122 6 947 p 001 ca19 9 hr 2 230 95 ci 1 297 3 835 p 004 tnm stage hr 3 864 95 ci 1 819 8 207 p 001 lymph node metastasis hr 1 679 95 ci 1 005 2 805 p 048 margin status hr 1 873 95 ci 1 063 3 300 p 030 independent prognostic factors median survival time low nlr ca19 9 group better high nlr ca19 9 group p 05 preoperative nlr serum ca19 9 associated prognosis patients gbc high nlr high ca19 9 predictors poor long term outcome among patients gbc undergoing curative surgery pubmed","probabilities":0.9799733,"Title":"Prognostic significance of neutrophil-lymphocyte ratio and carbohydrate antigen 19-9 in patients with gallbladder carcinoma","Abstract":"The neutrophil-lymphocyte ratio (NLR) is an immune response-related indicator and it is associated with poor prognosis of various cancers. The carbohydrate antigen19-9 (CA19-9) is a tumor-associated antigen and it has prognostic relevance in gallbladder carcinoma (GBC). We aimed to analyze whether preoperative NLR and serum CA19-9 were associated with outcomes of GBC patients after surgery with curative intent.Between January 2010 and May 2015, 90 resectable GBC patients who underwent curative surgery in our institution were included. All final diagnoses were confirmed by pathologic examination. The demographics, clinical, and histopathology data were analyzed. The Cox regression proportional hazard model and Kaplan-Meier method were used to assess prognostic factors.The cutoff values of 4.33 and 250.90 U/mL were defined as high NLR and high CA19-9, respectively. The univariate analyses showed that TNM stage, lymph node metastasis, the degree of tumor differentiation, margin status, combined hepatectomy, CA19-9, NLR, and PNI were all associated with overall survival (P < .05). According to the multivariable analysis, NLR (hazard ratio (HR) 3.840, 95% confidence interval (95% CI): 2.122-6.947, P < .001), CA19-9 (HR 2.230, 95% CI: 1.297-3.835, P = .004), TNM stage (HR 3.864, 95% CI: 1.819-8.207, P < .001), lymph node metastasis (HR 1.679, 95% CI: 1.005-2.805, P = .048), and margin status (HR 1.873, 95% CI: 1.063-3.300, P = .030) were independent prognostic factors. The median survival time in low NLR and CA19-9 group was better than high NLR and CA19-9 group (P < .05).The preoperative NLR and serum CA19-9 are associated with prognosis of patients with GBC. High NLR and high CA19-9 were predictors of poor long-term outcome among patients with GBC undergoing curative surgery.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of neutrophil-lymphocyte ratio and carbohydrate antigen 19-9 in patients with gallbladder carcinoma The neutrophil-lymphocyte ratio (NLR) is an immune response-related indicator and it is associated with poor prognosis of various cancers. The carbohydrate antigen19-9 (CA19-9) is a tumor-associated antigen and it has prognostic relevance in gallbladder carcinoma (GBC). We aimed to analyze whether preoperative NLR and serum CA19-9 were associated with outcomes of GBC patients after surgery with curative intent.Between January 2010 and May 2015, 90 resectable GBC patients who underwent curative surgery in our institution were included. All final diagnoses were confirmed by pathologic examination. The demographics, clinical, and histopathology data were analyzed. The Cox regression proportional hazard model and Kaplan-Meier method were used to assess prognostic factors.The cutoff values of 4.33 and 250.90 U/mL were defined as high NLR and high CA19-9, respectively. The univariate analyses showed that TNM stage, lymph node metastasis, the degree of tumor differentiation, margin status, combined hepatectomy, CA19-9, NLR, and PNI were all associated with overall survival (P < .05). According to the multivariable analysis, NLR (hazard ratio (HR) 3.840, 95% confidence interval (95% CI): 2.122-6.947, P < .001), CA19-9 (HR 2.230, 95% CI: 1.297-3.835, P = .004), TNM stage (HR 3.864, 95% CI: 1.819-8.207, P < .001), lymph node metastasis (HR 1.679, 95% CI: 1.005-2.805, P = .048), and margin status (HR 1.873, 95% CI: 1.063-3.300, P = .030) were independent prognostic factors. The median survival time in low NLR and CA19-9 group was better than high NLR and CA19-9 group (P < .05).The preoperative NLR and serum CA19-9 are associated with prognosis of patients with GBC. High NLR and high CA19-9 were predictors of poor long-term outcome among patients with GBC undergoing curative surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"triptolide induces phase arrest apoptosis gallbladder cancer cells gallbladder carcinoma common malignancy biliary tract low 5 year survival rate extremely poor prognosis thus new effective treatments drugs urgently needed treatment malignancy study first time investigated effects triptolide gallbladder cancer cells identified mechanisms underlying potential anticancer effects mtt assay showed triptolide decreased cell viability dose time dependent manner results colony formation assay indicated triptolide strongly suppressed colony formation ability gbc sd sgc 996 cells flow cytometric analysis revealed triptolide induced phase arrest gallbladder cancer cells addition triptolide induced apoptosis shown results annexin v propidium iodide double staining hoechst 33342 staining furthermore triptolide decreased mitochondrial membrane potential m dose dependent manner finally western blot analysis triptolide treated cells revealed activation caspase 3 caspase 9 parp bcl 2 result demonstrated triptolide induced apoptosis gallbladder cancer cells regulating apoptosis related protein expression suggests triptolide may promising drug treat gallbladder carcinoma stn","probabilities":0.9467213,"Title":"Triptolide Induces S Phase Arrest And Apoptosis In Gallbladder Cancer Cells","Abstract":"Gallbladder carcinoma is the most common malignancy of the biliary tract, with a very low 5-year survival rate and extremely poor prognosis. Thus, new effective treatments and drugs are urgently needed for the treatment of this malignancy. In this study, for the first time we investigated the effects of triptolide on gallbladder cancer cells and identified the mechanisms underlying its potential anticancer effects. The MTT assay showed that triptolide decreased cell viability in a dose- and time-dependent manner. The results of the colony formation assay indicated that triptolide strongly suppressed colony formation ability in GBC-SD and SGC-996 cells. Flow cytometric analysis revealed that triptolide induced S phase arrest in gallbladder cancer cells. In addition, triptolide induced apoptosis, as shown by the results of annexin V/propidium iodide double-staining and Hoechst 33342 staining. Furthermore, triptolide decreased mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Finally, western blot analysis of triptolide-treated cells revealed the activation of caspase-3, caspase-9, PARP, and Bcl-2; this result demonstrated that triptolide induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that triptolide may be a promising drug to treat gallbladder carcinoma.","Source":"STN","category":"ANIMAL","training_data":"Triptolide Induces S Phase Arrest And Apoptosis In Gallbladder Cancer Cells Gallbladder carcinoma is the most common malignancy of the biliary tract, with a very low 5-year survival rate and extremely poor prognosis. Thus, new effective treatments and drugs are urgently needed for the treatment of this malignancy. In this study, for the first time we investigated the effects of triptolide on gallbladder cancer cells and identified the mechanisms underlying its potential anticancer effects. The MTT assay showed that triptolide decreased cell viability in a dose- and time-dependent manner. The results of the colony formation assay indicated that triptolide strongly suppressed colony formation ability in GBC-SD and SGC-996 cells. Flow cytometric analysis revealed that triptolide induced S phase arrest in gallbladder cancer cells. In addition, triptolide induced apoptosis, as shown by the results of annexin V/propidium iodide double-staining and Hoechst 33342 staining. Furthermore, triptolide decreased mitochondrial membrane potential (ΔΨm) in a dose-dependent manner. Finally, western blot analysis of triptolide-treated cells revealed the activation of caspase-3, caspase-9, PARP, and Bcl-2; this result demonstrated that triptolide induced apoptosis in gallbladder cancer cells by regulating apoptosis-related protein expression, and suggests that triptolide may be a promising drug to treat gallbladder carcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"use dna methylation distinguish gallbladder carcinoma background gallbladder cancer gbc uncommon malignancy high mortality rate often diagnosed late due lack early symptoms relative hidden nature gallbladder despite advancements imaging technologies reliable screening test gbc role aberrant dna methylation process tumorigenesis individual genes genome wide scale well elucidated occurs early cancer development thus capable serving screening marker methods panel design methylation data tumor samples 12 types n 4 772 adjacent normal 8 types n 411 normal white blood cells n 656 tcga gse compared differentially methylated sites derived using bayesian hierarchical model dss adjusted p value 0 05 panel covers 80 672 cpg sites spanning 1 05mb human genome panel contains 12 196 gbc relevant cpg sites performed targeted bisulfite sequencing 23 gbc patients 6 stage ii iii 17 stage iv 13 patients non malignant gallbladder diseases cholecystitis gallstones 23 gbc patients obtained adjacent normal tissue 7 basic clinical features age gender patients gbc patients non malignant gallbladder diseases comparable results among 12 196 gbc relevant cpg sites 10 216 sites statistically significantly hypermethylated 275 sites statistically significantly hypomethylated comparing patients non malignant gallbladder disease well adjacent normal gallbladder tissues subsequently used derived differentially methylated cpg sites construct linear regression model achieving area curve 99 collectively methylation levels comparable tissues non malignant disease adjacent normal interestingly considering 275 hypomethylated markers alone observed methylation level adjacent normal tissues significantly higher tissues non malignant disease conclusions collectively panel effectively distinguish gbc samples non cancerous samples demonstrating potential dna methylation gbc screening furthermore hypomethylation markers used distinguish non malignant disease healthy google scholar","probabilities":1.0,"Title":"Use Of Dna Methylation To Distinguish Gallbladder Carcinoma","Abstract":"Background: Gallbladder cancer (GBC), an uncommon malignancy with a high mortality rate, is often diagnosed late due to lack of early symptoms and the relative hidden nature of the gallbladder. Despite the advancements in imaging technologies, there is no reliable screening test for GBC. The role of aberrant DNA methylation in the process of tumorigenesis both at individual genes and a genome-wide scale has been well elucidated. It occurs very early in cancer development, thus capable of serving as a screening marker. Methods: Panel Design: Methylation data of tumor samples (12 types, n = 4,772), adjacent normal (8 types, n = 411), and normal white blood cells (n = 656) from TCGA and GSE were compared. Differentially methylated sites were derived using a Bayesian hierarchical model-DSS with an adjusted p-value < 0.05. Our panel covers 80,672 CpG sites, spanning 1.05Mb of human genome. This panel contains 12,196 GBC relevant CpG sites. We performed targeted bisulfite sequencing on 23 GBC patients (6 stage II-III, 17 stage IV) and 13 patients with non-malignant gallbladder diseases (cholecystitis and gallstones). Of the 23 GBC patients, we obtained adjacent normal tissue from 7 of them. Basic clinical features such as age, gender, of patients with GBC and patients with non-malignant gallbladder diseases were comparable. Results: Among the 12,196 GBC relevant CpG sites, 10,216 sites were statistically significantly hypermethylated and 275 sites were statistically significantly hypomethylated comparing to patients with non-malignant gallbladder disease as well as adjacent normal gallbladder tissues. Subsequently, we used the derived differentially methylated CpG sites to construct a linear regression model, achieving an area under curve of 99%. Collectively, the methylation levels were comparable between tissues with non-malignant disease and adjacent normal. Interestingly, when considering the 275 hypomethylated markers alone, we observed that the methylation level of adjacent normal tissues is significantly higher than tissues with non-malignant disease. Conclusions: Collectively, our panel can effectively distinguish GBC samples from non-cancerous samples, demonstrating the potential of DNA methylation in GBC screening. Furthermore, hypomethylation markers can be used to distinguish non-malignant disease from the healthy.","Source":"Google Scholar","category":"ANIMAL","training_data":"Use Of Dna Methylation To Distinguish Gallbladder Carcinoma Background: Gallbladder cancer (GBC), an uncommon malignancy with a high mortality rate, is often diagnosed late due to lack of early symptoms and the relative hidden nature of the gallbladder. Despite the advancements in imaging technologies, there is no reliable screening test for GBC. The role of aberrant DNA methylation in the process of tumorigenesis both at individual genes and a genome-wide scale has been well elucidated. It occurs very early in cancer development, thus capable of serving as a screening marker. Methods: Panel Design: Methylation data of tumor samples (12 types, n = 4,772), adjacent normal (8 types, n = 411), and normal white blood cells (n = 656) from TCGA and GSE were compared. Differentially methylated sites were derived using a Bayesian hierarchical model-DSS with an adjusted p-value < 0.05. Our panel covers 80,672 CpG sites, spanning 1.05Mb of human genome. This panel contains 12,196 GBC relevant CpG sites. We performed targeted bisulfite sequencing on 23 GBC patients (6 stage II-III, 17 stage IV) and 13 patients with non-malignant gallbladder diseases (cholecystitis and gallstones). Of the 23 GBC patients, we obtained adjacent normal tissue from 7 of them. Basic clinical features such as age, gender, of patients with GBC and patients with non-malignant gallbladder diseases were comparable. Results: Among the 12,196 GBC relevant CpG sites, 10,216 sites were statistically significantly hypermethylated and 275 sites were statistically significantly hypomethylated comparing to patients with non-malignant gallbladder disease as well as adjacent normal gallbladder tissues. Subsequently, we used the derived differentially methylated CpG sites to construct a linear regression model, achieving an area under curve of 99%. Collectively, the methylation levels were comparable between tissues with non-malignant disease and adjacent normal. Interestingly, when considering the 275 hypomethylated markers alone, we observed that the methylation level of adjacent normal tissues is significantly higher than tissues with non-malignant disease. Conclusions: Collectively, our panel can effectively distinguish GBC samples from non-cancerous samples, demonstrating the potential of DNA methylation in GBC screening. Furthermore, hypomethylation markers can be used to distinguish non-malignant disease from the healthy. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"comparative analysis clinical characteristics histomorphologic immunohistochemical spectrum gallbladder carcinoma young adults 45 years elderly adults 60 years gallbladder carcinoma gbc frequent 60 years age behavior young adults much studied retrospective analysis performed patients underwent cholecystectomy procedure years 2001 2016 group young patients 45 compared elderly patients 60 years reference various clinical histomorphologic immunohistochemical parameters statistical analysis performed using test fisher test survival curves calculated kaplan meier actuarial survival curves log rank tests one hundred one patients gbc observed study period 14 patients 13 9 belonged study group age range 20 45 years 43 patients 42 6 constituted comparison elderly control group age range 60 80 years forty four pts middle aged group 46 59 years thus excluded study reference age 45 60 significant difference found sex females 64 3 vs 69 8 p 0 7 presence gall stones 64 vs 60 p 0 8 advanced disease presentation t4 14 3 vs 7 p 0 40 incidental detection gallbladder carcinoma 28 5 vs 28 p 0 9 tumor stage presentation stage ii 35 7 vs 49 p 0 39 poor differentiation tumor grades g3 14 vs 12 p 0 79 full length involvement 28 5 vs 11 6 p 0 015 gallbladder abundant tumor necrosis 43 vs 14 p 0 021 common younger patients group whereas adenosquamous pure squamous cell carcinoma predominantly observed elderly patients immunohistochemical studies showed higher percentage overexpression p53 ki 67 proliferation indices younger population overall survival younger patients 48 months whereas elderly patients 36 months histological markers denoting aggressive tumor behavior observed gallbladder carcinomas younger individuals studies needed delineate differences molecular mechanisms involved progression tumor two groups stn","probabilities":1.0,"Title":"A Comparative Analysis Of Clinical Characteristics And Histomorphologic And Immunohistochemical Spectrum Of Gallbladder Carcinoma In Young Adults (< 45 Years) And Elderly Adults (> 60 Years)","Abstract":"Gallbladder carcinoma (GBC) is more frequent after 60 years of age; its behavior in young adults has not been much studied. A retrospective analysis was performed in patients who underwent a cholecystectomy procedure between the years 2001 to 2016. A group of young patients (< 45) were compared with elderly patients (> 60 years) with reference to various clinical, histomorphologic, and immunohistochemical parameters. Statistical analysis was performed using t test and Fisher's test. Survival curves were calculated by Kaplan-Meier actuarial survival curves and log-rank tests. One hundred and one patients with GBC were observed during the study period. Of these, 14 patients (13.9%) belonged to the study group (age range 20 to 45 years) and 43 patients (42.6%) constituted the comparison elderly control group (age range 60 to 80 years). Forty-four pts. were in the middle-aged group (46 to 59 years) and were thus excluded from the study. With reference to age (< 45 and > 60), no significant difference was found in sex (females 64.3% vs 69.8%, p = 0.7), presence of gall stones (64% vs 60%, p = 0.8), advanced disease at presentation (T4) (14.3% vs 7%, p = 0.40), incidental detection of gallbladder carcinoma (28.5% vs 28%, p = 0.9), tumor stage at presentation (stage I/II) (35.7% vs 49%, p = 0.39), and poor differentiation (tumor grades G3) (14% vs 12%, p = 0.79). Full-length involvement (28.5% vs 11.6%, p = 0.015) of the gallbladder and abundant tumor necrosis (43% vs 14%, p = 0.021) were more common in the younger patients group whereas adenosquamous and pure squamous cell carcinoma were predominantly observed in elderly patients. Immunohistochemical studies showed higher percentage of overexpression of p53 and Ki-67 proliferation indices in the younger population. Overall survival in younger patients was 48 months whereas in elderly patients it was 36 months. Histological markers denoting aggressive tumor behavior were observed in gallbladder carcinomas of younger individuals; further studies are needed to delineate the differences in molecular mechanisms involved in progression of the tumor in the two groups.","Source":"STN","category":"HUMAN","training_data":"A Comparative Analysis Of Clinical Characteristics And Histomorphologic And Immunohistochemical Spectrum Of Gallbladder Carcinoma In Young Adults (< 45 Years) And Elderly Adults (> 60 Years) Gallbladder carcinoma (GBC) is more frequent after 60 years of age; its behavior in young adults has not been much studied. A retrospective analysis was performed in patients who underwent a cholecystectomy procedure between the years 2001 to 2016. A group of young patients (< 45) were compared with elderly patients (> 60 years) with reference to various clinical, histomorphologic, and immunohistochemical parameters. Statistical analysis was performed using t test and Fisher's test. Survival curves were calculated by Kaplan-Meier actuarial survival curves and log-rank tests. One hundred and one patients with GBC were observed during the study period. Of these, 14 patients (13.9%) belonged to the study group (age range 20 to 45 years) and 43 patients (42.6%) constituted the comparison elderly control group (age range 60 to 80 years). Forty-four pts. were in the middle-aged group (46 to 59 years) and were thus excluded from the study. With reference to age (< 45 and > 60), no significant difference was found in sex (females 64.3% vs 69.8%, p = 0.7), presence of gall stones (64% vs 60%, p = 0.8), advanced disease at presentation (T4) (14.3% vs 7%, p = 0.40), incidental detection of gallbladder carcinoma (28.5% vs 28%, p = 0.9), tumor stage at presentation (stage I/II) (35.7% vs 49%, p = 0.39), and poor differentiation (tumor grades G3) (14% vs 12%, p = 0.79). Full-length involvement (28.5% vs 11.6%, p = 0.015) of the gallbladder and abundant tumor necrosis (43% vs 14%, p = 0.021) were more common in the younger patients group whereas adenosquamous and pure squamous cell carcinoma were predominantly observed in elderly patients. Immunohistochemical studies showed higher percentage of overexpression of p53 and Ki-67 proliferation indices in the younger population. Overall survival in younger patients was 48 months whereas in elderly patients it was 36 months. Histological markers denoting aggressive tumor behavior were observed in gallbladder carcinomas of younger individuals; further studies are needed to delineate the differences in molecular mechanisms involved in progression of the tumor in the two groups. STN","prediction_labels":"HUMAN"},{"cleaned":"multicentre european study preoperative biliary drainage hilar cholangiocarcinoma background indications preoperative biliary drainage pbd context hepatectomy hilar malignancies still debated aim study investigate current european practice regarding biliary drainage hepatectomy klatskin tumours methods retrospective analysis patients underwent formal extended right left hepatectomy hilar cholangiocarcinoma 1997 2008 11 european teaching hospitals details serum bilirubin levels admission time surgery available pbd performed physicians discretion primary outcome 90 day mortality secondary outcomes morbidity cause death association pbd preoperative serum bilirubin levels postoperative mortality assessed logistic regression entire population well separately right left sided hepatectomy groups adjusted confounding factors results total 366 patients enrolled pbd performed 180 patients overall mortality rate 10 7 per cent higher right left sided hepatectomy 14 7 versus 6 6 per cent adjusted odds ratio 3 16 95 per cent confidence interval 1 50 6 65 p 0 001 pbd affect overall postoperative mortality associated decreased mortality rate right hepatectomy adjusted 0 29 0 11 0 77 p 0 013 increased mortality rate left hepatectomy adjusted 4 06 1 01 16 30 p 0 035 preoperative serum bilirubin level greater 50 mol l also associated increased mortality right hepatectomy adjusted 7 02 1 73 28 52 p 0 002 conclusion pbd affect overall mortality jaundiced patients hilar cholangiocarcinoma may difference patients undergoing right sided versus left sided hepatectomy pubmed","probabilities":0.9799733,"Title":"Multicentre European study of preoperative biliary drainage for hilar cholangiocarcinoma","Abstract":"BACKGROUND: Indications for preoperative biliary drainage (PBD) in the context of hepatectomy for hilar malignancies are still debated. The aim of this study was to investigate current European practice regarding biliary drainage before hepatectomy for Klatskin tumours. METHODS: This was a retrospective analysis of all patients who underwent formal or extended right or left hepatectomy for hilar cholangiocarcinoma between 1997 and 2008 at 11 European teaching hospitals, and for whom details of serum bilirubin levels at admission and at the time of surgery were available. PBD was performed at the physicians' discretion. The primary outcome was 90-day mortality. Secondary outcomes were morbidity and cause of death. The association of PBD and of preoperative serum bilirubin levels with postoperative mortality was assessed by logistic regression, in the entire population as well as separately in the right- and left-sided hepatectomy groups, and was adjusted for confounding factors. RESULTS: A total of 366 patients were enrolled; PBD was performed in 180 patients. The overall mortality rate was 10·7 per cent and was higher after right- than left-sided hepatectomy (14·7 versus 6·6 per cent; adjusted odds ratio (OR) 3·16, 95 per cent confidence interval 1·50 to 6·65; P = 0·001). PBD did not affect overall postoperative mortality, but was associated with a decreased mortality rate after right hepatectomy (adjusted OR 0·29, 0·11 to 0·77; P = 0·013) and an increased mortality rate after left hepatectomy (adjusted OR 4·06, 1·01 to 16·30; P = 0·035). A preoperative serum bilirubin level greater than 50 µmol/l was also associated with increased mortality, but only after right hepatectomy (adjusted OR 7·02, 1·73 to 28·52; P = 0·002). CONCLUSION: PBD does not affect overall mortality in jaundiced patients with hilar cholangiocarcinoma, but there may be a difference between patients undergoing right-sided versus left-sided hepatectomy.","Source":"PubMed","category":"HUMAN","training_data":"Multicentre European study of preoperative biliary drainage for hilar cholangiocarcinoma BACKGROUND: Indications for preoperative biliary drainage (PBD) in the context of hepatectomy for hilar malignancies are still debated. The aim of this study was to investigate current European practice regarding biliary drainage before hepatectomy for Klatskin tumours. METHODS: This was a retrospective analysis of all patients who underwent formal or extended right or left hepatectomy for hilar cholangiocarcinoma between 1997 and 2008 at 11 European teaching hospitals, and for whom details of serum bilirubin levels at admission and at the time of surgery were available. PBD was performed at the physicians' discretion. The primary outcome was 90-day mortality. Secondary outcomes were morbidity and cause of death. The association of PBD and of preoperative serum bilirubin levels with postoperative mortality was assessed by logistic regression, in the entire population as well as separately in the right- and left-sided hepatectomy groups, and was adjusted for confounding factors. RESULTS: A total of 366 patients were enrolled; PBD was performed in 180 patients. The overall mortality rate was 10·7 per cent and was higher after right- than left-sided hepatectomy (14·7 versus 6·6 per cent; adjusted odds ratio (OR) 3·16, 95 per cent confidence interval 1·50 to 6·65; P = 0·001). PBD did not affect overall postoperative mortality, but was associated with a decreased mortality rate after right hepatectomy (adjusted OR 0·29, 0·11 to 0·77; P = 0·013) and an increased mortality rate after left hepatectomy (adjusted OR 4·06, 1·01 to 16·30; P = 0·035). A preoperative serum bilirubin level greater than 50 µmol/l was also associated with increased mortality, but only after right hepatectomy (adjusted OR 7·02, 1·73 to 28·52; P = 0·002). CONCLUSION: PBD does not affect overall mortality in jaundiced patients with hilar cholangiocarcinoma, but there may be a difference between patients undergoing right-sided versus left-sided hepatectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extended radical cholecystectomy gallbladder cancer long term outcomes indications limitations aim delineate indications limitations extended radical cholecystectomy gallbladder cancer procedure instituted department 1982 methods 145 patients underwent radical resection gallbladder cancer 1982 2006 52 36 extended radical cholecystectomy involved en bloc resection gallbladder gallbladder fossa extrahepatic bile duct regional lymph nodes first second echelon node groups retrospective analysis 52 patients conducted including least 5 years follow residual tumor status judged residual tumor r0 microscopic macroscopic residual tumor r1 2 pathological findings documented according american joint committee cancer cancer staging manual 7th edition results primary tumor classified pathological t1 pt1 3 patients pt2 36 pt3 12 pt4 1 twenty three patients lymph node metastases 11 single positive node 4 two positive nodes 8 three positive nodes none three patients pt1 tumors nodal disease whereas 23 49 47 pt2 advanced tumors nodal disease one patient died hospital stay definitive resection giving hospital mortality rate 2 overall survival os extended radical cholecystectomy 65 5 years 53 10 years 52 patients os differed according pt classification p 0 001 nodal status p 0 010 3 patients pt1 tumors 29 36 patients pt2 tumors survived 5 years 12 patients pt3 tumors 8 r1 2 resection distant metastasis extensive extrahepatic organ involvement died soon resection remaining four pt3 patients localized hepatic spread gallbladder fossa underwent r0 resection 2 survived 5 years another survived 4 years 2 mo patient pt4 tumor died disease soon resection among 23 node positive patients 11 survived 5 years 10 modest degree nodal disease one two positive nodes conclusion extended radical cholecystectomy indicated pt2 tumors pt3 tumors localized hepatic invasion provided regional nodal disease limited modest degree two positive nodes extensive pt3 disease pt4 disease marked nodal disease appears beyond scope radical procedure pubmed","probabilities":0.9799733,"Title":"Extended radical cholecystectomy for gallbladder cancer: long-term outcomes, indications and limitations","Abstract":"AIM: To delineate indications and limitations for \"extended\" radical cholecystectomy for gallbladder cancer: a procedure which was instituted in our department in 1982. METHODS: Of 145 patients who underwent a radical resection for gallbladder cancer from 1982 through 2006, 52 (36%) had an extended radical cholecystectomy, which involved en bloc resection of the gallbladder, gallbladder fossa, extrahepatic bile duct, and the regional lymph nodes (first- and second-echelon node groups). A retrospective analysis of the 52 patients was conducted including at least 5 years of follow up. Residual tumor status was judged as no residual tumor (R0) or microscopic/macroscopic residual tumor (R1-2). Pathological findings were documented according to the American Joint Committee on Cancer Cancer Staging Manual (7th edition). RESULTS: The primary tumor was classified as pathological T1 (pT1) in 3 patients, pT2 in 36, pT3 in 12, and pT4 in 1. Twenty-three patients had lymph node metastases; 11 had a single positive node, 4 had two positive nodes, and 8 had three or more positive nodes. None of the three patients with pT1 tumors had nodal disease, whereas 23 of 49 (47%) with pT2 or more advanced tumors had nodal disease. One patient died during the hospital stay for definitive resection, giving an in-hospital mortality rate of 2%. Overall survival (OS) after extended radical cholecystectomy was 65% at 5 years and 53% at 10 years in all 52 patients. OS differed according to the pT classification (P < 0.001) and the nodal status (P = 0.010). All of 3 patients with pT1 tumors and most (29 of 36) patients with pT2 tumors survived for more than 5 years. Of 12 patients with pT3 tumors, 8 who had an R1-2 resection, distant metastasis, or extensive extrahepatic organ involvement died soon after resection. Of the remaining four pT3 patients who had localized hepatic spread through the gallbladder fossa and underwent an R0 resection, 2 survived for more than 5 years and another survived for 4 years and 2 mo. The only patient with pT4 tumor died of disease soon after resection. Among 23 node-positive patients, 11 survived for more than 5 years, and of these, 10 had a modest degree of nodal disease (one or two positive nodes). CONCLUSION: Extended radical cholecystectomy is indicated for pT2 tumors and some pT3 tumors with localized hepatic invasion, provided that the regional nodal disease is limited to a modest degree (up to two positive nodes). Extensive pT3 disease, pT4 disease, or marked nodal disease appears to be beyond the scope of this radical procedure.","Source":"PubMed","category":"HUMAN","training_data":"Extended radical cholecystectomy for gallbladder cancer: long-term outcomes, indications and limitations AIM: To delineate indications and limitations for \"extended\" radical cholecystectomy for gallbladder cancer: a procedure which was instituted in our department in 1982. METHODS: Of 145 patients who underwent a radical resection for gallbladder cancer from 1982 through 2006, 52 (36%) had an extended radical cholecystectomy, which involved en bloc resection of the gallbladder, gallbladder fossa, extrahepatic bile duct, and the regional lymph nodes (first- and second-echelon node groups). A retrospective analysis of the 52 patients was conducted including at least 5 years of follow up. Residual tumor status was judged as no residual tumor (R0) or microscopic/macroscopic residual tumor (R1-2). Pathological findings were documented according to the American Joint Committee on Cancer Cancer Staging Manual (7th edition). RESULTS: The primary tumor was classified as pathological T1 (pT1) in 3 patients, pT2 in 36, pT3 in 12, and pT4 in 1. Twenty-three patients had lymph node metastases; 11 had a single positive node, 4 had two positive nodes, and 8 had three or more positive nodes. None of the three patients with pT1 tumors had nodal disease, whereas 23 of 49 (47%) with pT2 or more advanced tumors had nodal disease. One patient died during the hospital stay for definitive resection, giving an in-hospital mortality rate of 2%. Overall survival (OS) after extended radical cholecystectomy was 65% at 5 years and 53% at 10 years in all 52 patients. OS differed according to the pT classification (P < 0.001) and the nodal status (P = 0.010). All of 3 patients with pT1 tumors and most (29 of 36) patients with pT2 tumors survived for more than 5 years. Of 12 patients with pT3 tumors, 8 who had an R1-2 resection, distant metastasis, or extensive extrahepatic organ involvement died soon after resection. Of the remaining four pT3 patients who had localized hepatic spread through the gallbladder fossa and underwent an R0 resection, 2 survived for more than 5 years and another survived for 4 years and 2 mo. The only patient with pT4 tumor died of disease soon after resection. Among 23 node-positive patients, 11 survived for more than 5 years, and of these, 10 had a modest degree of nodal disease (one or two positive nodes). CONCLUSION: Extended radical cholecystectomy is indicated for pT2 tumors and some pT3 tumors with localized hepatic invasion, provided that the regional nodal disease is limited to a modest degree (up to two positive nodes). Extensive pT3 disease, pT4 disease, or marked nodal disease appears to be beyond the scope of this radical procedure. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative risk score prediction long term outcomes hepatectomy intrahepatic cholangiocarcinoma background accurate prediction prognosis patients intrahepatic cholangiocarcinoma icc remains challenge sought define preoperative risk tool predict long term survival resection icc study design patients underwent hepatectomy icc 1 16 major hepatobiliary centers 1990 2015 identified clinicopathologic data analyzed prognostic model developed based regression coefficients data training set model subsequently assessed using validation set results among 538 patients patients solitary tumor median tumor number 1 interquartile range 1 2 median tumor size 5 7 cm interquartile range 4 0 8 0 cm median 5 year overall survival 39 0 months 39 0 respectively multivariable analyses preoperative factors associated long term survival included tumor size hazard ratio hr 1 12 95 ci 1 06 1 18 natural logarithm carbohydrate antigen 19 9 level hr 1 33 95 ci 1 22 1 45 albumin level hr 0 76 95 ci 0 55 0 99 neutrophil lymphocyte ratio hr 1 05 95 ci 1 02 1 09 weighted composite prognostic score constructed based factors 9 1 12 tumor size 2 81 natural logarithm carbohydrate antigen 19 9 0 50 neutrophil lymphocyte ratio 2 79 albumin model demonstrated good performance testing area curve 0 696 validation 0 691 datasets model performed better categories area curve 0 532 cumulative stage classifications american joint committee cancer staging manual 8th edition area curve 0 559 assessing risk death within 1 year operation risk score 25 positive predictive value 59 8 compared positive predictive value 35 3 american joint committee cancer staging manual 8th edition t4 disease 31 8 stage iiib disease conclusions postsurgical long term outcomes predicted using composite weighted scoring system based preoperative clinical parameters preoperative risk model used inform patient provider conversations expectations operation pubmed","probabilities":0.9799733,"Title":"Preoperative Risk Score and Prediction of Long-Term Outcomes after Hepatectomy for Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: Accurate prediction of prognosis for patients with intrahepatic cholangiocarcinoma (ICC) remains a challenge. We sought to define a preoperative risk tool to predict long-term survival after resection of ICC. STUDY DESIGN: Patients who underwent hepatectomy for ICC at 1 of 16 major hepatobiliary centers between 1990 and 2015 were identified. Clinicopathologic data were analyzed and a prognostic model was developed based on the regression β-coefficients on data in training set. The model was subsequently assessed using a validation set. RESULTS: Among 538 patients, most patients had a solitary tumor (median tumor number 1; interquartile range 1 to 2) and median tumor size was 5.7 cm (interquartile range 4.0 to 8.0 cm). Median and 5-year overall survival was 39.0 months and 39.0%, respectively. On multivariable analyses, preoperative factors associated with long-term survival included tumor size (hazard ratio [HR] 1.12; 95% CI 1.06 to 1.18), natural logarithm carbohydrate antigen 19-9 level (HR 1.33; 95% CI 1.22 to 1.45), albumin level (HR 0.76; 95% CI 0.55 to 0.99), and neutrophil to lymphocyte ratio (HR 1.05; 95% CI 1.02 to 1.09). A weighted composite prognostic score was constructed based on these factors: [9 + (1.12 × tumor size) + (2.81 × natural logarithm carbohydrate antigen 19-9) + (0.50 × neutrophil to lymphocyte ratio) + (-2.79 × albumin)]. The model demonstrated good performance in the testing (area under the curve 0.696) and validation (0.691) datasets. The model performed better than both the T categories (area under the curve 0.532) and the cumulative stage classifications in the American Joint Committee on Cancer staging manual, 8th edition (area under the curve 0.559). When assessing risk of death within 1 year of operation, a risk score ≥25 had a positive predictive value of 59.8% compared with a positive predictive value of 35.3% for American Joint Committee on Cancer staging manual, 8th edition T4 disease and 31.8% for stage IIIB disease. CONCLUSIONS: Postsurgical long-term outcomes could be predicted using a composite weighted scoring system based on preoperative clinical parameters. The preoperative risk model can be used to inform patient to provider conversations and expectations before operation.","Source":"PubMed","category":"HUMAN","training_data":"Preoperative Risk Score and Prediction of Long-Term Outcomes after Hepatectomy for Intrahepatic Cholangiocarcinoma BACKGROUND: Accurate prediction of prognosis for patients with intrahepatic cholangiocarcinoma (ICC) remains a challenge. We sought to define a preoperative risk tool to predict long-term survival after resection of ICC. STUDY DESIGN: Patients who underwent hepatectomy for ICC at 1 of 16 major hepatobiliary centers between 1990 and 2015 were identified. Clinicopathologic data were analyzed and a prognostic model was developed based on the regression β-coefficients on data in training set. The model was subsequently assessed using a validation set. RESULTS: Among 538 patients, most patients had a solitary tumor (median tumor number 1; interquartile range 1 to 2) and median tumor size was 5.7 cm (interquartile range 4.0 to 8.0 cm). Median and 5-year overall survival was 39.0 months and 39.0%, respectively. On multivariable analyses, preoperative factors associated with long-term survival included tumor size (hazard ratio [HR] 1.12; 95% CI 1.06 to 1.18), natural logarithm carbohydrate antigen 19-9 level (HR 1.33; 95% CI 1.22 to 1.45), albumin level (HR 0.76; 95% CI 0.55 to 0.99), and neutrophil to lymphocyte ratio (HR 1.05; 95% CI 1.02 to 1.09). A weighted composite prognostic score was constructed based on these factors: [9 + (1.12 × tumor size) + (2.81 × natural logarithm carbohydrate antigen 19-9) + (0.50 × neutrophil to lymphocyte ratio) + (-2.79 × albumin)]. The model demonstrated good performance in the testing (area under the curve 0.696) and validation (0.691) datasets. The model performed better than both the T categories (area under the curve 0.532) and the cumulative stage classifications in the American Joint Committee on Cancer staging manual, 8th edition (area under the curve 0.559). When assessing risk of death within 1 year of operation, a risk score ≥25 had a positive predictive value of 59.8% compared with a positive predictive value of 35.3% for American Joint Committee on Cancer staging manual, 8th edition T4 disease and 31.8% for stage IIIB disease. CONCLUSIONS: Postsurgical long-term outcomes could be predicted using a composite weighted scoring system based on preoperative clinical parameters. The preoperative risk model can be used to inform patient to provider conversations and expectations before operation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"p53 status prognostic role extrahepatic bile duct cancer meta analysis published studies dysfunction p53 common genetic alteration human cancer variety studies investigated clinicopathologic correlation p53 impact patient survival different types cancer extrahepatic bile duct cancer ebdc however results limited conflicting study performed investigation confirm whether correlation p53 status routine parameters observe impact p53 survival ebdc patients meta analysis based published studies conducted candidate studies searched pubmed embase isi web science results demonstrated significant correlations p53 expression clinicopathological parameters furthermore pooled results meta analysis showed combined hazard ratio hr estimate overall survival os 1 53 95 ci 1 10 2 14 1 23 95 ci 0 93 1 75 univariate multivariate analysis respectively conclusion high level p53 appears effective prognostic factor os ebdc patients however limitations unavoidable meta analysis problems previous p53 studies ebdc mean studies necessary significant conclusions made pubmed","probabilities":0.8684211,"Title":"p53 status and its prognostic role in extrahepatic bile duct cancer: a meta-analysis of published studies","Abstract":"The dysfunction of p53 is the most common genetic alteration in human cancer. A variety of studies have investigated the clinicopathologic correlation of p53 and its impact on patient survival in different types of cancer. For extrahepatic bile duct cancer (EBDC), however, the results were limited and conflicting. In this study, we performed an investigation to confirm whether there was a correlation between p53 status and some routine parameters. To further observe the impact of p53 on the survival of EBDC patients, a meta-analysis based on published studies was conducted. Candidate studies were searched from PubMed, EMBASE, and ISI Web of Science. Our results demonstrated that there were significant correlations between p53 expression and some clinicopathological parameters. Furthermore, the pooled results of the meta-analysis showed that the combined hazard ratio (HR) estimate for overall survival (OS) was 1.53 (95% CI, 1.10-2.14) and 1.23 (95% CI, 0.93-1.75) in univariate and multivariate analysis, respectively. In conclusion, the high level of p53 appears to be an effective prognostic factor to OS of EBDC patients. However, some limitations unavoidable in this meta-analysis and problems of previous p53 studies in EBDC mean that further studies are necessary before significant conclusions can be made.","Source":"PubMed","category":"HUMAN","training_data":"p53 status and its prognostic role in extrahepatic bile duct cancer: a meta-analysis of published studies The dysfunction of p53 is the most common genetic alteration in human cancer. A variety of studies have investigated the clinicopathologic correlation of p53 and its impact on patient survival in different types of cancer. For extrahepatic bile duct cancer (EBDC), however, the results were limited and conflicting. In this study, we performed an investigation to confirm whether there was a correlation between p53 status and some routine parameters. To further observe the impact of p53 on the survival of EBDC patients, a meta-analysis based on published studies was conducted. Candidate studies were searched from PubMed, EMBASE, and ISI Web of Science. Our results demonstrated that there were significant correlations between p53 expression and some clinicopathological parameters. Furthermore, the pooled results of the meta-analysis showed that the combined hazard ratio (HR) estimate for overall survival (OS) was 1.53 (95% CI, 1.10-2.14) and 1.23 (95% CI, 0.93-1.75) in univariate and multivariate analysis, respectively. In conclusion, the high level of p53 appears to be an effective prognostic factor to OS of EBDC patients. However, some limitations unavoidable in this meta-analysis and problems of previous p53 studies in EBDC mean that further studies are necessary before significant conclusions can be made. PubMed","prediction_labels":"HUMAN"},{"cleaned":"serum nardilysin surrogate marker epithelial mesenchymal transition predicts prognosis intrahepatic cholangiocarcinoma surgical resection purpose studies investigated prognostic biomarkers patients intrahepatic cholangiocarcinoma icc nardilysin nrdc metalloendopeptidase m16 family suggested play important roles inflammation several cancer types herein examined clinical significance biological function nrdc icc experimental design measured serum nrdc levels 98 patients icc underwent surgical resection two independent cohorts assess prognostic impact also analyzed nrdc mrna levels cancerous tissue specimens 43 patients icc investigated roles nrdc cell proliferation migration gemcitabine sensitivity gene expression icc cell lines using gene silencing results high serum nrdc levels associated shorter overall survival disease free survival primary n 79 validation n 19 cohorts correlation observed serum protein levels cancerous tissue mrna levels nrdc spearman 0 413 p 0 006 gene knockdown nrdc icc cell lines attenuated cell proliferation migration tumor growth xenografts increased sensitivity gemcitabine gene knockdown nrdc also accompanied significant changes expression several epithelial mesenchymal transition emt related genes strong correlations observed mrna levels nrdc emt inducing transcription factors zeb1 snai1 surgical specimens patients icc conclusions serum nrdc possible surrogate marker reflecting emt state primary tumors predicts outcome icc surgical resection stn","probabilities":0.9467213,"Title":"Serum Nardilysin A Surrogate Marker For Epithelial-Mesenchymal Transition Predicts Prognosis Of Intrahepatic Cholangiocarcinoma After Surgical Resection","Abstract":"Purpose: Few studies have investigated prognostic biomarkers in patients with intrahepatic cholangiocarcinoma (ICC). Nardilysin (NRDC), a metalloendopeptidase of the M16 family, has been suggested to play important roles in inflammation and several cancer types. We herein examined the clinical significance and biological function of NRDC in ICC.Experimental Design: We measured serum NRDC levels in 98 patients with ICC who underwent surgical resection in two independent cohorts to assess its prognostic impact. We also analyzed NRDC mRNA levels in cancerous tissue specimens from 43 patients with ICC. We investigated the roles of NRDC in cell proliferation, migration, gemcitabine sensitivity, and gene expression in ICC cell lines using gene silencing. \n\n Results: High serum NRDC levels were associated with shorter overall survival and disease-free survival in the primary (n = 79) and validation (n = 19) cohorts. A correlation was observed between serum protein levels and cancerous tissue mRNA levels of NRDC (Spearman ρ = 0.413; P = 0.006). The gene knockdown of NRDC in ICC cell lines attenuated cell proliferation, migration, and tumor growth in xenografts, and increased sensitivity to gemcitabine. The gene knockdown of NRDC was also accompanied by significant changes in the expression of several epithelial-mesenchymal transition (EMT)-related genes. Strong correlations were observed between the mRNA levels of NRDC and EMT-inducing transcription factors, ZEB1 and SNAI1, in surgical specimens from patients with ICC. \n\n Conclusions: Serum NRDC, a possible surrogate marker reflecting the EMT state in primary tumors, predicts the outcome of ICC after surgical resection.","Source":"STN","category":"ANIMAL","training_data":"Serum Nardilysin A Surrogate Marker For Epithelial-Mesenchymal Transition Predicts Prognosis Of Intrahepatic Cholangiocarcinoma After Surgical Resection Purpose: Few studies have investigated prognostic biomarkers in patients with intrahepatic cholangiocarcinoma (ICC). Nardilysin (NRDC), a metalloendopeptidase of the M16 family, has been suggested to play important roles in inflammation and several cancer types. We herein examined the clinical significance and biological function of NRDC in ICC.Experimental Design: We measured serum NRDC levels in 98 patients with ICC who underwent surgical resection in two independent cohorts to assess its prognostic impact. We also analyzed NRDC mRNA levels in cancerous tissue specimens from 43 patients with ICC. We investigated the roles of NRDC in cell proliferation, migration, gemcitabine sensitivity, and gene expression in ICC cell lines using gene silencing. \n\n Results: High serum NRDC levels were associated with shorter overall survival and disease-free survival in the primary (n = 79) and validation (n = 19) cohorts. A correlation was observed between serum protein levels and cancerous tissue mRNA levels of NRDC (Spearman ρ = 0.413; P = 0.006). The gene knockdown of NRDC in ICC cell lines attenuated cell proliferation, migration, and tumor growth in xenografts, and increased sensitivity to gemcitabine. The gene knockdown of NRDC was also accompanied by significant changes in the expression of several epithelial-mesenchymal transition (EMT)-related genes. Strong correlations were observed between the mRNA levels of NRDC and EMT-inducing transcription factors, ZEB1 and SNAI1, in surgical specimens from patients with ICC. \n\n Conclusions: Serum NRDC, a possible surrogate marker reflecting the EMT state in primary tumors, predicts the outcome of ICC after surgical resection. STN","prediction_labels":"ANIMAL"},{"cleaned":"tumor size predicts vascular invasion histologic grade among patients undergoing resection intrahepatic cholangiocarcinoma association tumor size survival patients intrahepatic cholangiocarcinoma icc undergoing surgical resection controversial sought define incidence major microscopic vascular invasion relative icc tumor size identify predictors microscopic vascular invasion patients icc 5 cm total 443 patients undergoing surgical resection icc 1973 2011 one 11 participating institutions identified clinical pathologic data evaluated using uni multivariate analyses tumor sized increased incidence microscopic vascular invasion increased 3 cm 3 6 3 5 cm 24 7 5 7 cm 38 3 7 15 cm 32 9 15 cm 55 6 p 0 001 increasing tumor size also found associated worsening tumor grade incidence poorly differentiated tumors increased increasing icc tumor size 3 cm 9 7 3 5 cm 19 8 5 7 cm 24 2 7 15 cm 21 1 15 cm 31 6 p 0 04 presence perineural invasion odds ratio 2 98 regional lymph node metastasis 4 43 independently associated increased risk microscopic vascular invasion tumors 5 cm p 0 05 risk microscopic vascular invasion worse tumor grade increased tumor size large tumors likely harbor worse pathologic features information considered determining therapy prognosis patients large icc pubmed","probabilities":0.9799733,"Title":"Tumor size predicts vascular invasion and histologic grade among patients undergoing resection of intrahepatic cholangiocarcinoma","Abstract":"The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection is controversial. We sought to define the incidence of major and microscopic vascular invasion relative to ICC tumor size, and identify predictors of microscopic vascular invasion in patients with ICC ≥5 cm. A total of 443 patients undergoing surgical resection for ICC between 1973 and 2011 at one of 11 participating institutions were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. As tumor sized increased, the incidence of microscopic vascular invasion increased: <3 cm, 3.6 %; 3-5 cm, 24.7 %; 5-7 cm, 38.3 %; 7-15 cm, 32.9 %, ≥15 cm, 55.6 %; (p < 0.001). Increasing tumor size was also found to be associated with worsening tumor grade. The incidence of poorly differentiated tumors increased with increasing ICC tumor size: <3 cm, 9.7 %; 3-5 cm, 19.8 %; 5-7 cm, 24.2 %; 7-15 cm, 21.1 %; >15 cm, 31.6 % (p = 0.04). The presence of perineural invasion (odds ratio [OR] = 2.98) and regional lymph node metastasis (OR = 4.43) were independently associated with an increased risk of microscopic vascular invasion in tumors ≥5 cm (both p < 0.05). Risk of microscopic vascular invasion and worse tumor grade increased with tumor size. Large tumors likely harbor worse pathologic features; this information should be considered when determining therapy and prognosis of patients with large ICC.","Source":"PubMed","category":"HUMAN","training_data":"Tumor size predicts vascular invasion and histologic grade among patients undergoing resection of intrahepatic cholangiocarcinoma The association between tumor size and survival in patients with intrahepatic cholangiocarcinoma (ICC) undergoing surgical resection is controversial. We sought to define the incidence of major and microscopic vascular invasion relative to ICC tumor size, and identify predictors of microscopic vascular invasion in patients with ICC ≥5 cm. A total of 443 patients undergoing surgical resection for ICC between 1973 and 2011 at one of 11 participating institutions were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. As tumor sized increased, the incidence of microscopic vascular invasion increased: <3 cm, 3.6 %; 3-5 cm, 24.7 %; 5-7 cm, 38.3 %; 7-15 cm, 32.9 %, ≥15 cm, 55.6 %; (p < 0.001). Increasing tumor size was also found to be associated with worsening tumor grade. The incidence of poorly differentiated tumors increased with increasing ICC tumor size: <3 cm, 9.7 %; 3-5 cm, 19.8 %; 5-7 cm, 24.2 %; 7-15 cm, 21.1 %; >15 cm, 31.6 % (p = 0.04). The presence of perineural invasion (odds ratio [OR] = 2.98) and regional lymph node metastasis (OR = 4.43) were independently associated with an increased risk of microscopic vascular invasion in tumors ≥5 cm (both p < 0.05). Risk of microscopic vascular invasion and worse tumor grade increased with tumor size. Large tumors likely harbor worse pathologic features; this information should be considered when determining therapy and prognosis of patients with large ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"influence marital status survival adults extrahepatic intrahepatic cholangiocarcinoma although prognostic value marital status implicated many cancers prognostic impact cholangiocarcinoma yet determined aim study examine association marital status cholangiocarcinoma survival included 8 776 extrahepatic cholangiocarcinoma cases 1 352 intrahepatic cholangiocarcinoma cases 1973 2013 surveillance epidemiology end results database found widowed patients likely female aged 70 low income areas multivariate analysis indicated marital status independent prognostic factor extrahepatic cholangiocarcinoma patients subgroup analysis suggested widowed status independently predicted poor survival regional stage older patients intrahepatic cholangiocarcinoma conclude marital status valuable prognostic factor cholangiocarcinoma widowed patients greater risk death others stn","probabilities":0.9799733,"Title":"Influence Of Marital Status On The Survival Of Adults With Extrahepatic/Intrahepatic Cholangiocarcinoma","Abstract":"Although the prognostic value of marital status has been implicated in many cancers, its prognostic impact on cholangiocarcinoma has not yet been determined. The aim of this study was to examine the association between marital status and cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from the Surveillance, Epidemiology, and End Results database. We found widowed patients were more likely to be female, aged more than 70, and from low income areas. Multivariate analysis indicated that marital status was an independent prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis suggested the widowed status independently predicted poor survival at regional stage and in older patients with intrahepatic cholangiocarcinoma. To conclude, marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed patients are at greater risk of death than others.","Source":"STN","category":"HUMAN","training_data":"Influence Of Marital Status On The Survival Of Adults With Extrahepatic/Intrahepatic Cholangiocarcinoma Although the prognostic value of marital status has been implicated in many cancers, its prognostic impact on cholangiocarcinoma has not yet been determined. The aim of this study was to examine the association between marital status and cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from the Surveillance, Epidemiology, and End Results database. We found widowed patients were more likely to be female, aged more than 70, and from low income areas. Multivariate analysis indicated that marital status was an independent prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis suggested the widowed status independently predicted poor survival at regional stage and in older patients with intrahepatic cholangiocarcinoma. To conclude, marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed patients are at greater risk of death than others. STN","prediction_labels":"HUMAN"},{"cleaned":"second line chemotherapy advanced biliary cancers retrospective multicenter analysis outcomes background although gemcitabine plus platinum chemotherapy established first line regimen advanced biliary cancer abc standard second line therapy study evaluated current practice outcomes second line chemotherapy patients abc across 3 us academic medical centers methods institutional registries reviewed identify patients received second line chemotherapy abc april 2010 march 2015 along demographics diagnoses staging treatment histories clinical outcomes overall survival initiation second line chemotherapy os2 estimated kaplan meier methods results study identified 198 patients cholangiocarcinoma intrahepatic 61 1 extrahepatic 14 1 gallbladder carcinoma 24 8 52 received least 3 lines systemic chemotherapy median os2 11 months 95 confidence interval ci 8 8 13 1 months median os2 patients intrahepatic cholangiocarcinoma 13 4 months 95 ci 10 7 17 8 months longer patients extrahepatic cholangiocarcinoma 6 8 months 95 ci 5 10 6 months gallbladder carcinoma 9 4 months 95 ci 7 2 12 3 months p 018 median time second line treatment failure 2 2 months 95 ci 1 8 2 7 months similar across tumor locations p 60 conclusions large cohort patients abc treated across 3 academic medical centers failure first line chemotherapy time treatment failure standard therapies short although median os2 longer reported previously half patients received additional lines treatment multicenter collaboration represents largest cohort studied date second line chemotherapy abc provides contemporary benchmark future clinical trials pubmed","probabilities":0.9799733,"Title":"Second-line chemotherapy in advanced biliary cancers: A retrospective, multicenter analysis of outcomes","Abstract":"BACKGROUND: Although gemcitabine plus platinum chemotherapy is the established first-line regimen for advanced biliary cancer (ABC), there is no standard second-line therapy. This study evaluated current practice and outcomes for second-line chemotherapy in patients with ABC across 3 US academic medical centers. METHODS: Institutional registries were reviewed to identify patients who had received second-line chemotherapy for ABC from April 2010 to March 2015 along with their demographics, diagnoses and staging, treatment histories, and clinical outcomes. Overall survival from the initiation of second-line chemotherapy (OS2) was estimated with Kaplan-Meier methods. RESULTS: This study identified 198 patients with cholangiocarcinoma (intrahepatic [61.1%] or extrahepatic [14.1%]) or gallbladder carcinoma (24.8%); 52% received at least 3 lines of systemic chemotherapy. The median OS2 was 11 months (95% confidence interval [CI], 8.8-13.1 months). The median OS2 for patients with intrahepatic cholangiocarcinoma was 13.4 months (95% CI, 10.7-17.8 months), which was longer than that for patients with extrahepatic cholangiocarcinoma (6.8 months; 95% CI, 5-10.6 months) or gallbladder carcinoma (9.4 months; 95% CI, 7.2-12.3 months; P = .018). The median time to second-line treatment failure was 2.2 months (95% CI, 1.8-2.7 months), and it was similar across tumor locations (P = .60). CONCLUSIONS: In this large cohort of patients with ABC treated across 3 academic medical centers after the failure of first-line chemotherapy, the time to treatment failure on standard therapies was short, although the median OS2 was longer than has been reported previously, and more than half of the patients received additional lines of treatment. This multicenter collaboration represents the largest cohort studied to date of second-line chemotherapy for ABC and provides a contemporary benchmark for future clinical trials.","Source":"PubMed","category":"HUMAN","training_data":"Second-line chemotherapy in advanced biliary cancers: A retrospective, multicenter analysis of outcomes BACKGROUND: Although gemcitabine plus platinum chemotherapy is the established first-line regimen for advanced biliary cancer (ABC), there is no standard second-line therapy. This study evaluated current practice and outcomes for second-line chemotherapy in patients with ABC across 3 US academic medical centers. METHODS: Institutional registries were reviewed to identify patients who had received second-line chemotherapy for ABC from April 2010 to March 2015 along with their demographics, diagnoses and staging, treatment histories, and clinical outcomes. Overall survival from the initiation of second-line chemotherapy (OS2) was estimated with Kaplan-Meier methods. RESULTS: This study identified 198 patients with cholangiocarcinoma (intrahepatic [61.1%] or extrahepatic [14.1%]) or gallbladder carcinoma (24.8%); 52% received at least 3 lines of systemic chemotherapy. The median OS2 was 11 months (95% confidence interval [CI], 8.8-13.1 months). The median OS2 for patients with intrahepatic cholangiocarcinoma was 13.4 months (95% CI, 10.7-17.8 months), which was longer than that for patients with extrahepatic cholangiocarcinoma (6.8 months; 95% CI, 5-10.6 months) or gallbladder carcinoma (9.4 months; 95% CI, 7.2-12.3 months; P = .018). The median time to second-line treatment failure was 2.2 months (95% CI, 1.8-2.7 months), and it was similar across tumor locations (P = .60). CONCLUSIONS: In this large cohort of patients with ABC treated across 3 academic medical centers after the failure of first-line chemotherapy, the time to treatment failure on standard therapies was short, although the median OS2 was longer than has been reported previously, and more than half of the patients received additional lines of treatment. This multicenter collaboration represents the largest cohort studied to date of second-line chemotherapy for ABC and provides a contemporary benchmark for future clinical trials. PubMed","prediction_labels":"HUMAN"},{"cleaned":"targeted gene sequencing gallbladder carcinoma identifies high impact somatic rare germline mutations background gallbladder carcinoma gbc subtype biliary tract malignancy poor prognosis high fatality rate present study designed uncover somatic rare germline mutations gbc reveal disease biology understand clinical importance mutation profile terms prognostics actionability materials methods performed ultra deep sequencing across 409 cancer related genes 11 gbc patients north indian descent ngs data analysis performed using ion reporter several publicly available resources databases results identified 184 nonsynonymous somatic 60 rare germline mutations bona fide cancer drivers smad family member 4 smad4 lysine methyltransferase 2c kmt2c tumor protein p53 tp53 early onset cases hypermutated cases harbored mutation critical dna repair genes additionally detected 9 novel genes high impact somatic mutations gbc conclusion results indicated significance inherited rare germline mutations dna repair pathway genes addition acquired somatic mutations gb carcinogenesis pubmed","probabilities":0.9799733,"Title":"Targeted Gene Sequencing of Gallbladder Carcinoma Identifies High-impact Somatic and Rare Germline Mutations","Abstract":"BACKGROUND: Gallbladder carcinoma (GBC) is a subtype of biliary tract malignancy with poor prognosis and high fatality rate. The present study was designed to uncover somatic and rare germline mutations in GBC to reveal the disease biology and understand the clinical importance of mutation profile in terms of prognostics and actionability. MATERIALS AND METHODS: We performed ultra-deep sequencing across 409 cancer-related genes in 11 GBC patients of North-Indian descent. NGS data analysis was performed using Ion Reporter and several other publicly available resources and databases. RESULTS: We identified 184 nonsynonymous somatic and 60 rare germline mutations in bona-fide cancer drivers such as SMAD family member 4 (SMAD4), lysine methyltransferase 2C (KMT2C), and tumor protein p53 (TP53). All the early-onset cases or hypermutated cases harbored mutation(s) in critical DNA-repair genes. Additionally, we detected 9 novel genes with high-impact somatic mutations in GBC. CONCLUSION: Our results indicated the significance of inherited rare germline mutations in DNA-repair pathway genes in addition to acquired somatic mutations in GB carcinogenesis.","Source":"PubMed","category":"HUMAN","training_data":"Targeted Gene Sequencing of Gallbladder Carcinoma Identifies High-impact Somatic and Rare Germline Mutations BACKGROUND: Gallbladder carcinoma (GBC) is a subtype of biliary tract malignancy with poor prognosis and high fatality rate. The present study was designed to uncover somatic and rare germline mutations in GBC to reveal the disease biology and understand the clinical importance of mutation profile in terms of prognostics and actionability. MATERIALS AND METHODS: We performed ultra-deep sequencing across 409 cancer-related genes in 11 GBC patients of North-Indian descent. NGS data analysis was performed using Ion Reporter and several other publicly available resources and databases. RESULTS: We identified 184 nonsynonymous somatic and 60 rare germline mutations in bona-fide cancer drivers such as SMAD family member 4 (SMAD4), lysine methyltransferase 2C (KMT2C), and tumor protein p53 (TP53). All the early-onset cases or hypermutated cases harbored mutation(s) in critical DNA-repair genes. Additionally, we detected 9 novel genes with high-impact somatic mutations in GBC. CONCLUSION: Our results indicated the significance of inherited rare germline mutations in DNA-repair pathway genes in addition to acquired somatic mutations in GB carcinogenesis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"early estimates seer cancer incidence 2014 background cancer incidence rates trends cases diagnosed 2014 using data reported surveillance epidemiology end results seer program february 2016 validation rates trends cases diagnosed 2013 submitted february 2015 using november 2015 submission reported new cancer sites include pancreas kidney renal pelvis corpus uterus childhood cancer sites ages birth 19 years inclusive methods new reporting delay model presented estimates consistent results model used usual november seer submissions adjusting large case undercount february submission joinpoint regression methodology used assess trends delay adjusted rates trends checked validity february 2016 november 2016 submissions results validation revealed delay model provides similar estimates eventual counts using either february november submission data trends declined 2014 prostate colon rectum cancer males females male female lung cancer cervical cancer thyroid cancer liver intrahepatic bile duct cancer increased pancreas male female corpus uterus cancer demonstrated modest increase slight increases occurred male kidney renal pelvis childhood cancer sites ages birth 19 years conclusions evaluating early cancer data submissions adjusted reporting delay produces timely valid incidence rates trends results current study support using delay adjusted february submission data valid incidence rate trend estimates several data cycles cancer 2017 123 2524 34 2017 american cancer society pubmed","probabilities":0.9799733,"Title":"Early estimates of SEER cancer incidence, 2014","Abstract":"BACKGROUND: Cancer incidence rates and trends for cases diagnosed through 2014 using data reported to the Surveillance, Epidemiology, and End Results (SEER) program in February 2016 and a validation of rates and trends for cases diagnosed through 2013 and submitted in February 2015 using the November 2015 submission are reported. New cancer sites include the pancreas, kidney and renal pelvis, corpus and uterus, and childhood cancer sites for ages birth to 19 years inclusive. METHODS: A new reporting delay model is presented for these estimates for more consistent results with the model used for the usual November SEER submissions, adjusting for the large case undercount in the February submission. Joinpoint regression methodology was used to assess trends. Delay-adjusted rates and trends were checked for validity between the February 2016 and November 2016 submissions. RESULTS: Validation revealed that the delay model provides similar estimates of eventual counts using either February or November submission data. Trends declined through 2014 for prostate and colon and rectum cancer for males and females, male and female lung cancer, and cervical cancer. Thyroid cancer and liver and intrahepatic bile duct cancer increased. Pancreas (male and female) and corpus and uterus cancer demonstrated a modest increase. Slight increases occurred for male kidney and renal pelvis, and for all childhood cancer sites for ages birth to 19 years. CONCLUSIONS: Evaluating early cancer data submissions, adjusted for reporting delay, produces timely and valid incidence rates and trends. The results of the current study support using delay-adjusted February submission data for valid incidence rate and trend estimates over several data cycles. Cancer 2017;123:2524-34. © 2017 American Cancer Society.","Source":"PubMed","category":"HUMAN","training_data":"Early estimates of SEER cancer incidence, 2014 BACKGROUND: Cancer incidence rates and trends for cases diagnosed through 2014 using data reported to the Surveillance, Epidemiology, and End Results (SEER) program in February 2016 and a validation of rates and trends for cases diagnosed through 2013 and submitted in February 2015 using the November 2015 submission are reported. New cancer sites include the pancreas, kidney and renal pelvis, corpus and uterus, and childhood cancer sites for ages birth to 19 years inclusive. METHODS: A new reporting delay model is presented for these estimates for more consistent results with the model used for the usual November SEER submissions, adjusting for the large case undercount in the February submission. Joinpoint regression methodology was used to assess trends. Delay-adjusted rates and trends were checked for validity between the February 2016 and November 2016 submissions. RESULTS: Validation revealed that the delay model provides similar estimates of eventual counts using either February or November submission data. Trends declined through 2014 for prostate and colon and rectum cancer for males and females, male and female lung cancer, and cervical cancer. Thyroid cancer and liver and intrahepatic bile duct cancer increased. Pancreas (male and female) and corpus and uterus cancer demonstrated a modest increase. Slight increases occurred for male kidney and renal pelvis, and for all childhood cancer sites for ages birth to 19 years. CONCLUSIONS: Evaluating early cancer data submissions, adjusted for reporting delay, produces timely and valid incidence rates and trends. The results of the current study support using delay-adjusted February submission data for valid incidence rate and trend estimates over several data cycles. Cancer 2017;123:2524-34. © 2017 American Cancer Society. PubMed","prediction_labels":"HUMAN"},{"cleaned":"combination therapy capecitabine cisplatin second line chemotherapy advanced biliary tract cancer background aims palliative chemotherapy main treatment advanced biliary tract cancer btc however lack established second line chemotherapy treat disease progression first line chemotherapy examined combination therapy capecitabine cisplatin advanced btc second line regimen methods analyzed medical records 40 patients diagnosed btc received palliative second line chemotherapy capecitabine cisplatin results median overall survival start second line chemotherapy 6 3 months median overall survival diagnosis 17 9 months median progression free survival second line chemotherapy 2 3 months nine 30 patients experienced adverse events grade 3 eastern cooperative oncology group performance score independent predictor adverse events conclusions combination therapy capecitabine cisplatin may option second line chemotherapy patients advanced btc pubmed","probabilities":0.9799733,"Title":"Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer","Abstract":"BACKGROUND/AIMS: Palliative chemotherapy is the main treatment for advanced biliary tract cancer (BTC). However, there is a lack of established second-line chemotherapy to treat disease progression after first-line chemotherapy. We examined combination therapy with capecitabine and cisplatin for advanced BTC as a second-line regimen. METHODS: We analyzed the medical records of 40 patients diagnosed with BTC who received palliative second-line chemotherapy with capecitabine and cisplatin. RESULTS: The median overall survival from the start of second-line chemotherapy was 6.3 months. The median overall survival from diagnosis was 17.9 months. The median progression-free survival during second-line chemotherapy was 2.3 months. Nine (30%) patients experienced adverse events of grade ≥3. Eastern Cooperative Oncology Group performance score was an independent predictor of adverse events. CONCLUSIONS: Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC.","Source":"PubMed","category":"HUMAN","training_data":"Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer BACKGROUND/AIMS: Palliative chemotherapy is the main treatment for advanced biliary tract cancer (BTC). However, there is a lack of established second-line chemotherapy to treat disease progression after first-line chemotherapy. We examined combination therapy with capecitabine and cisplatin for advanced BTC as a second-line regimen. METHODS: We analyzed the medical records of 40 patients diagnosed with BTC who received palliative second-line chemotherapy with capecitabine and cisplatin. RESULTS: The median overall survival from the start of second-line chemotherapy was 6.3 months. The median overall survival from diagnosis was 17.9 months. The median progression-free survival during second-line chemotherapy was 2.3 months. Nine (30%) patients experienced adverse events of grade ≥3. Eastern Cooperative Oncology Group performance score was an independent predictor of adverse events. CONCLUSIONS: Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"serum mir 26a diagnostic prognostic biomarker cholangiocarcinoma order determine diagnostic prognostic value mir 26a cholangiocarcinoma cca compared mir 26a levels serum 66 cca patients 66 healthy controls followed serum analysis pre operative serum post operative serum cca patients found concentration levels mir 26a serum cca patients significantly higher healthy controls p 0 01 furthermore concentration levels mir 26a post operative serum significantly reduced compared pre operative serum p 0 001 high mir 26a serum correlated significantly clinical stage distant metastasis differentiation status poor survival cca patients importantly serum mir 26a independent prognostic marker cca conclusion results suggested mir 26a serum might potential useful noninvasive biomarker early detection cca pubmed","probabilities":0.9799733,"Title":"Serum miR-26a as a diagnostic and prognostic biomarker in cholangiocarcinoma","Abstract":"In order to determine the diagnostic and prognostic value of miR-26a in Cholangiocarcinoma (CCA), we compared miR-26a levels in serum from 66 CCA patients and 66 healthy controls, which was followed by serum analysis between the pre-operative serum and post-operative serum of these CCA patients. We found the concentration levels of miR-26a in serum of CCA patients were significantly higher than that from healthy controls (P < 0.01). Furthermore, the concentration levels of miR-26a in the post-operative serum were significantly reduced when compared to the pre-operative serum (P < 0.001). High miR-26a in serum was correlated significantly with clinical stage, distant metastasis, differentiation status, and poor survival of CCA patients. More importantly, serum miR-26a was an independent prognostic marker for CCA. In conclusion, our results suggested that miR-26a in serum might be a potential and useful noninvasive biomarker for the early detection of CCA.","Source":"PubMed","category":"HUMAN","training_data":"Serum miR-26a as a diagnostic and prognostic biomarker in cholangiocarcinoma In order to determine the diagnostic and prognostic value of miR-26a in Cholangiocarcinoma (CCA), we compared miR-26a levels in serum from 66 CCA patients and 66 healthy controls, which was followed by serum analysis between the pre-operative serum and post-operative serum of these CCA patients. We found the concentration levels of miR-26a in serum of CCA patients were significantly higher than that from healthy controls (P < 0.01). Furthermore, the concentration levels of miR-26a in the post-operative serum were significantly reduced when compared to the pre-operative serum (P < 0.001). High miR-26a in serum was correlated significantly with clinical stage, distant metastasis, differentiation status, and poor survival of CCA patients. More importantly, serum miR-26a was an independent prognostic marker for CCA. In conclusion, our results suggested that miR-26a in serum might be a potential and useful noninvasive biomarker for the early detection of CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"chemoembolization degradable starch microspheres treatment patients primary recurrent unresectable locally advanced intrahepatic cholangiocarcinoma pilot study purpose evaluate efficacy complication rates tace degradable starch microspheres dsm tace patients unresectable intrahepatic cholangiocarcinoma icc without prior major liver resection mlr methods retrospective single center study 21 patients age 63 15 years either unresectable icc progressive systemic chemotherapy unresectable intrahepatic tumor recurrence prior mlr patients treated multi agent cisplatin doxorubicin mitomycin c dsm tace august 2012 july 2016 repeated 3 times 4 week intervals imaging response evaluated using recist 1 1 overall survival os complication rates stratified history mlr investigated results patients underwent total 64 dsm tace sessions two patients without mlr lost follow one uneventful dsm tace session one patient underwent living donor liver transplantation one dsm tace session yielding partial remission remaining 18 patients imaging response according recist 1 1 complete remission 2 18 11 1 pr 9 18 50 stable disease 7 18 38 9 yielding objective response rate 61 1 disease control rate 100 median os patients objective response significantly longer 18 0 months survival patients stable disease 4 8 months p 0 001 median os patients mlr 12 5 months similar patients without mlr 13 2 months 21 patients 2 9 5 developed post interventional hepatobiliary abscesses one patients died due subsequent sepsis conclusion dsm tace effective treatment unresectable otherwise therapy refractory intrahepatic cholangiocarcinoma even patients intrahepatic disease recurrence prior mlr level evidence level ii therapeutic study pubmed","probabilities":0.9799733,"Title":"Chemoembolization with Degradable Starch Microspheres for Treatment of Patients with Primary or Recurrent Unresectable, Locally Advanced Intrahepatic Cholangiocarcinoma: A Pilot Study","Abstract":"PURPOSE: To evaluate efficacy and complication rates of TACE with degradable starch microspheres (DSM-TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICC) with or without prior major liver resection (MLR). METHODS: This is a retrospective single-center study on 21 patients (age 63 ± 15 years) with either unresectable ICC progressive under systemic chemotherapy or unresectable intrahepatic tumor recurrence after prior MLR. Patients were treated by multi-agent (cisplatin/doxorubicin/mitomycin C) DSM-TACE between August 2012 and July 2016, repeated 3 times at 4-week intervals. Imaging response was evaluated using RECIST 1.1. Overall survival (OS) and complication rates, stratified by history of MLR, were investigated. RESULTS: Patients underwent a total 64 DSM-TACE sessions. Two patients (without MLR) were lost to follow-up after one uneventful DSM-TACE session. One patient underwent living-donor-liver transplantation after one DSM-TACE-session yielding partial remission. Of the remaining 18 patients, imaging response according to RECIST 1.1 was: complete remission in 2/18 (11.1%); PR in 9/18 (50%), and stable disease in 7/18 (38.9%), yielding an objective response rate of 61.1% and a disease control rate of 100%. Median OS of patients with objective response was significantly longer (18.0 months) than that of survival of patients with stable disease (4.8 months) (p = 0.001). Median OS of patients with MLR (12.5 months) was similar to that of patients without MLR (13.2 months). Of 21 patients, 2 (9.5%) developed post-interventional hepatobiliary abscesses, and one of these patients died due to subsequent sepsis. CONCLUSION: DSM-TACE is an effective treatment for unresectable and otherwise therapy-refractory intrahepatic cholangiocarcinoma, even in those patients with intrahepatic disease recurrence after prior MLR. LEVEL OF EVIDENCE: Level II, therapeutic study.","Source":"PubMed","category":"HUMAN","training_data":"Chemoembolization with Degradable Starch Microspheres for Treatment of Patients with Primary or Recurrent Unresectable, Locally Advanced Intrahepatic Cholangiocarcinoma: A Pilot Study PURPOSE: To evaluate efficacy and complication rates of TACE with degradable starch microspheres (DSM-TACE) in patients with unresectable intrahepatic cholangiocarcinoma (ICC) with or without prior major liver resection (MLR). METHODS: This is a retrospective single-center study on 21 patients (age 63 ± 15 years) with either unresectable ICC progressive under systemic chemotherapy or unresectable intrahepatic tumor recurrence after prior MLR. Patients were treated by multi-agent (cisplatin/doxorubicin/mitomycin C) DSM-TACE between August 2012 and July 2016, repeated 3 times at 4-week intervals. Imaging response was evaluated using RECIST 1.1. Overall survival (OS) and complication rates, stratified by history of MLR, were investigated. RESULTS: Patients underwent a total 64 DSM-TACE sessions. Two patients (without MLR) were lost to follow-up after one uneventful DSM-TACE session. One patient underwent living-donor-liver transplantation after one DSM-TACE-session yielding partial remission. Of the remaining 18 patients, imaging response according to RECIST 1.1 was: complete remission in 2/18 (11.1%); PR in 9/18 (50%), and stable disease in 7/18 (38.9%), yielding an objective response rate of 61.1% and a disease control rate of 100%. Median OS of patients with objective response was significantly longer (18.0 months) than that of survival of patients with stable disease (4.8 months) (p = 0.001). Median OS of patients with MLR (12.5 months) was similar to that of patients without MLR (13.2 months). Of 21 patients, 2 (9.5%) developed post-interventional hepatobiliary abscesses, and one of these patients died due to subsequent sepsis. CONCLUSION: DSM-TACE is an effective treatment for unresectable and otherwise therapy-refractory intrahepatic cholangiocarcinoma, even in those patients with intrahepatic disease recurrence after prior MLR. LEVEL OF EVIDENCE: Level II, therapeutic study. PubMed","prediction_labels":"HUMAN"},{"cleaned":"nomogram predicting benefit adjuvant chemoradiotherapy resected gallbladder cancer purpose although adjuvant chemoradiotherapy resected gallbladder cancer may improve survival patients identifying patients benefit remains challenging rarity disease specific aim study create decision aid help make individualized estimates potential survival benefit adjuvant chemoradiotherapy patients resected gallbladder cancer methods patients resected gallbladder cancer selected surveillance epidemiology end results seer medicare database diagnosed 1995 2005 covariates included age race sex stage receipt adjuvant chemotherapy chemoradiotherapy crt propensity score weighting used balance covariates treated untreated groups several types multivariate survival regression models constructed compared including cox proportional hazards weibull exponential log logistic lognormal models model performance compared using akaike information criterion primary end point overall survival without adjuvant chemotherapy crt results total 1 137 patients met inclusion criteria study lognormal survival model showed best performance web browser based nomogram built model make individualized estimates survival model predicts certain subsets patients least t2 n1 disease gain survival benefit adjuvant crt magnitude benefit individual patient vary conclusion nomogram built parametric survival model seer medicare database used decision aid predict gallbladder patients may benefit adjuvant crt pubmed","probabilities":0.9799733,"Title":"Nomogram for predicting the benefit of adjuvant chemoradiotherapy for resected gallbladder cancer","Abstract":"PURPOSE: Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer. METHODS: Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) -Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT. RESULTS: A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser-based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary. CONCLUSION: A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT.","Source":"PubMed","category":"HUMAN","training_data":"Nomogram for predicting the benefit of adjuvant chemoradiotherapy for resected gallbladder cancer PURPOSE: Although adjuvant chemoradiotherapy for resected gallbladder cancer may improve survival for some patients, identifying which patients will benefit remains challenging because of the rarity of this disease. The specific aim of this study was to create a decision aid to help make individualized estimates of the potential survival benefit of adjuvant chemoradiotherapy for patients with resected gallbladder cancer. METHODS: Patients with resected gallbladder cancer were selected from the Surveillance, Epidemiology, and End Results (SEER) -Medicare database who were diagnosed between 1995 and 2005. Covariates included age, race, sex, stage, and receipt of adjuvant chemotherapy or chemoradiotherapy (CRT). Propensity score weighting was used to balance covariates between treated and untreated groups. Several types of multivariate survival regression models were constructed and compared, including Cox proportional hazards, Weibull, exponential, log-logistic, and lognormal models. Model performance was compared using the Akaike information criterion. The primary end point was overall survival with or without adjuvant chemotherapy or CRT. RESULTS: A total of 1,137 patients met the inclusion criteria for the study. The lognormal survival model showed the best performance. A Web browser-based nomogram was built from this model to make individualized estimates of survival. The model predicts that certain subsets of patients with at least T2 or N1 disease will gain a survival benefit from adjuvant CRT, and the magnitude of benefit for an individual patient can vary. CONCLUSION: A nomogram built from a parametric survival model from the SEER-Medicare database can be used as a decision aid to predict which gallbladder patients may benefit from adjuvant CRT. PubMed","prediction_labels":"HUMAN"},{"cleaned":"distal cholangiocarcinoma pancreas adenocarcinoma really disease 13 institution study us extrahepatic biliary malignancy consortium central pancreas consortium background distal cholangiocarcinoma dc pancreatic ductal adenocarcinoma pdac often managed 1 entity yet direct comparisons lacking aim use 2 large multi institutional databases assess treatment pathologic survival differences diseases study design study included patients dc pdac underwent curative intent pancreaticoduodenectomy 2000 2015 13 institutions comprising us extrahepatic biliary malignancy central pancreas consortiums primary endpoint disease specific survival dss results 1 463 patients 224 15 dc 1 239 85 pdac compared pdac dc patients less likely margin positive 19 vs 25 p 0 005 lymph node ln positive 55 vs 69 p 0 001 receive adjuvant therapy 57 vs 71 p 0 001 dc patients treated adjuvant therapy 62 got gemcitabine alone 16 got gemcitabine cisplatin distal cholangiocarcinoma associated improved median dss 40 months compared pdac 22 months p 0 001 persisted multivariable analysis hazard ratio 0 65 95 ci 0 50 0 84 p 0 001 lymph node involvement factor independently associated decreased dss dc pdac dc ln positive patients similar dss pdac ln negative patients p 0 74 adjuvant therapy chemotherapy radiation associated improved median dss pdac ln positive patients 21 vs 13 months p 0 001 dc patients 38 vs 40 months p 0 62 regardless ln status conclusions distal cholangiocarcinoma pancreatic ductal adenocarcinoma distinct entities distal cholangiocarcinoma favorable prognosis compared pdac yet current adjuvant therapy regimens associated improved survival pdac dc therefore treatment paradigms used pdac extrapolated dc despite similar operative approaches novel therapies dc explored pubmed","probabilities":0.9799733,"Title":"Distal Cholangiocarcinoma and Pancreas Adenocarcinoma: Are They Really the Same Disease? A 13-Institution Study from the US Extrahepatic Biliary Malignancy Consortium and the Central Pancreas Consortium","Abstract":"BACKGROUND: Distal cholangiocarcinoma (DC) and pancreatic ductal adenocarcinoma (PDAC) are often managed as 1 entity, yet direct comparisons are lacking. Our aim was to use 2 large multi-institutional databases to assess treatment, pathologic, and survival differences between these diseases. STUDY DESIGN: This study included patients with DC and PDAC who underwent curative-intent pancreaticoduodenectomy from 2000 to 2015 at 13 institutions comprising the US Extrahepatic Biliary Malignancy and Central Pancreas Consortiums. Primary endpoint was disease-specific survival (DSS). RESULTS: Of 1,463 patients, 224 (15%) had DC and 1,239 (85%) had PDAC. Compared with PDAC, DC patients were less likely to be margin-positive (19% vs 25%; p = 0.005), lymph node (LN)-positive (55% vs 69%; p < 0.001), and receive adjuvant therapy (57% vs 71%; p < 0.001). Of DC patients treated with adjuvant therapy, 62% got gemcitabine alone and 16% got gemcitabine/cisplatin. Distal cholangiocarcinoma was associated with improved median DSS (40 months) compared with PDAC (22 months; p < 0.001), which persisted on multivariable analysis (hazard ratio 0.65; 95% CI 0.50 to 0.84; p = 0.001). Lymph node involvement was the only factor independently associated with decreased DSS for both DC and PDAC. The DC/LN-positive patients had similar DSS as PDAC/LN-negative patients (p = 0.74). Adjuvant therapy (chemotherapy ± radiation) was associated with improved median DSS for PDAC/LN-positive patients (21 vs 13 months; p = 0.001), but not for DC patients (38 vs 40 months; p = 0.62), regardless of LN status. CONCLUSIONS: Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are distinct entities. Distal cholangiocarcinoma has a favorable prognosis compared with PDAC, yet current adjuvant therapy regimens are only associated with improved survival in PDAC, not DC. Therefore, treatment paradigms used for PDAC should not be extrapolated to DC, despite similar operative approaches, and novel therapies for DC should be explored.","Source":"PubMed","category":"HUMAN","training_data":"Distal Cholangiocarcinoma and Pancreas Adenocarcinoma: Are They Really the Same Disease? A 13-Institution Study from the US Extrahepatic Biliary Malignancy Consortium and the Central Pancreas Consortium BACKGROUND: Distal cholangiocarcinoma (DC) and pancreatic ductal adenocarcinoma (PDAC) are often managed as 1 entity, yet direct comparisons are lacking. Our aim was to use 2 large multi-institutional databases to assess treatment, pathologic, and survival differences between these diseases. STUDY DESIGN: This study included patients with DC and PDAC who underwent curative-intent pancreaticoduodenectomy from 2000 to 2015 at 13 institutions comprising the US Extrahepatic Biliary Malignancy and Central Pancreas Consortiums. Primary endpoint was disease-specific survival (DSS). RESULTS: Of 1,463 patients, 224 (15%) had DC and 1,239 (85%) had PDAC. Compared with PDAC, DC patients were less likely to be margin-positive (19% vs 25%; p = 0.005), lymph node (LN)-positive (55% vs 69%; p < 0.001), and receive adjuvant therapy (57% vs 71%; p < 0.001). Of DC patients treated with adjuvant therapy, 62% got gemcitabine alone and 16% got gemcitabine/cisplatin. Distal cholangiocarcinoma was associated with improved median DSS (40 months) compared with PDAC (22 months; p < 0.001), which persisted on multivariable analysis (hazard ratio 0.65; 95% CI 0.50 to 0.84; p = 0.001). Lymph node involvement was the only factor independently associated with decreased DSS for both DC and PDAC. The DC/LN-positive patients had similar DSS as PDAC/LN-negative patients (p = 0.74). Adjuvant therapy (chemotherapy ± radiation) was associated with improved median DSS for PDAC/LN-positive patients (21 vs 13 months; p = 0.001), but not for DC patients (38 vs 40 months; p = 0.62), regardless of LN status. CONCLUSIONS: Distal cholangiocarcinoma and pancreatic ductal adenocarcinoma are distinct entities. Distal cholangiocarcinoma has a favorable prognosis compared with PDAC, yet current adjuvant therapy regimens are only associated with improved survival in PDAC, not DC. Therefore, treatment paradigms used for PDAC should not be extrapolated to DC, despite similar operative approaches, and novel therapies for DC should be explored. PubMed","prediction_labels":"HUMAN"},{"cleaned":"frozen sections liver intraoperative consultation requires skills gross examination histologic diagnosis well ability perform rapid interpretations time constraints aim review provide surgical pathologists framework dealing hepatic specimens frozen section area covering common clinical scenarios histologic findings differential diagnoses considered relation primary hepatic neoplasia metastatic diseases benign mimics malignancy pitfalls frozen section diagnosis lesional tissue covered finally assessment donor liver biopsy organ transplant evaluation discussed pubmed","probabilities":0.7966102,"Title":"Frozen Sections of the Liver","Abstract":"Intraoperative consultation requires skills in gross examination and histologic diagnosis, as well as an ability to perform rapid interpretations under time constraints. The aim of this review is to provide surgical pathologists with a framework for dealing with hepatic specimens in the frozen section area by covering common clinical scenarios and histologic findings. Differential diagnoses are considered in relation to primary hepatic neoplasia and metastatic diseases. Benign mimics of malignancy and other pitfalls in frozen section diagnosis of lesional tissue are covered. Finally, assessment of donor liver biopsy for organ transplant evaluation is discussed.","Source":"PubMed","category":"ANIMAL","training_data":"Frozen Sections of the Liver Intraoperative consultation requires skills in gross examination and histologic diagnosis, as well as an ability to perform rapid interpretations under time constraints. The aim of this review is to provide surgical pathologists with a framework for dealing with hepatic specimens in the frozen section area by covering common clinical scenarios and histologic findings. Differential diagnoses are considered in relation to primary hepatic neoplasia and metastatic diseases. Benign mimics of malignancy and other pitfalls in frozen section diagnosis of lesional tissue are covered. Finally, assessment of donor liver biopsy for organ transplant evaluation is discussed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"increased risk hepatobiliary cancers hospitalization autoimmune disease background aims autoimmune diseases associated increased risk liver cancer however comprehensive evaluation autoimmune diseases among patients develop different subtypes hepatobiliary cancer examined association autoimmune diseases cancers liver biliary tract swedish population methods analyzed data national datasets center primary health care research lund university sweden data patients autoimmune disorders retrieved swedish hospital discharge register 1964 2008 33 diseases evaluated hepatobiliary cancer cases retrieved swedish cancer registry calculated standardized incidence ratios sirs hazard ratios incident cancers deaths hepatobiliary cancers results among 402 462 patients autoimmune disorders 582 diagnosed primary liver cancer 330 gallbladder cancer 115 extrahepatic bile duct cancer 43 ampulla vater cancers identified 14 autoimmune conditions significantly associated increased risk primary liver cancer overall sir autoimmune disease 2 1 95 confidence interval ci 2 0 2 3 5 conditions associated gallbladder cancer overall sir 1 3 95 ci 1 1 1 4 3 associated extrahepatic bile duct cancer overall sir 1 6 95 ci 1 3 1 9 autoimmune disorders strongest association primary liver cancer primary biliary cirrhosis sir 39 5 95 ci 28 2 53 8 autoimmune hepatitis sir 29 0 95 ci 9 1 68 2 ulcerative colitis strongly associated extrahepatic bile duct cancer sir 5 6 95 ci 3 6 8 4 celiac disease crohn disease systemic sclerosis ulcerative colitis associated least 2 types cancer increased hazard ratios observed patients biliary tract cancer hospitalized autoimmune conditions conclusions study swedish population identified increased risk hepatobiliary cancers among individuals diagnosed autoimmune disease associations among different cancer types indicate shared immunomodulatory mechanisms determine susceptibility hepatobiliary cancer pubmed","probabilities":0.9799733,"Title":"Increased risk of hepatobiliary cancers after hospitalization for autoimmune disease","Abstract":"BACKGROUND & AIMS: Some autoimmune diseases are associated with increased risk of liver cancer. However, there has been no comprehensive evaluation of autoimmune diseases among patients who develop different subtypes of hepatobiliary cancer. We examined the association between autoimmune diseases and cancers of the liver and biliary tract in the Swedish population. METHODS: We analyzed data from national datasets at the Center for Primary Health Care Research (Lund University, Sweden). Data on patients with autoimmune disorders were retrieved from the Swedish Hospital Discharge Register, from 1964 through 2008; 33 diseases were evaluated. Hepatobiliary cancer cases were retrieved from the Swedish Cancer Registry. We calculated standardized incidence ratios (SIRs) and hazard ratios for incident cancers and deaths from hepatobiliary cancers. RESULTS: Among 402,462 patients with autoimmune disorders, 582 were diagnosed with primary liver cancer, 330 with gallbladder cancer, 115 with extrahepatic bile duct cancer, and 43 with ampulla of Vater cancers. We identified 14 autoimmune conditions that were significantly associated with increased risk of primary liver cancer (overall SIR [any autoimmune disease], 2.1; 95% confidence interval [CI], 2.0-2.3), 5 conditions associated with gallbladder cancer (overall SIR, 1.3; 95% CI, 1.1-1.4), and 3 associated with extrahepatic bile duct cancer (overall SIR, 1.6; 95% CI, 1.3-1.9). The autoimmune disorders with the strongest association with primary liver cancer were primary biliary cirrhosis (SIR, 39.5; 95% CI, 28.2-53.8) and autoimmune hepatitis (SIR, 29.0; 95% CI, 9.1-68.2); ulcerative colitis was strongly associated with extrahepatic bile duct cancer (SIR, 5.6; 95% CI, 3.6-8.4). Celiac disease, Crohn's disease, systemic sclerosis, and ulcerative colitis were associated with at least 2 types of cancer. Increased hazard ratios were observed only for patients with biliary tract cancer who had been hospitalized for autoimmune conditions. CONCLUSIONS: In a study of the Swedish population, we identified an increased risk of hepatobiliary cancers among individuals diagnosed with autoimmune disease. Associations among different cancer types indicate that shared immunomodulatory mechanisms determine susceptibility to hepatobiliary cancer.","Source":"PubMed","category":"HUMAN","training_data":"Increased risk of hepatobiliary cancers after hospitalization for autoimmune disease BACKGROUND & AIMS: Some autoimmune diseases are associated with increased risk of liver cancer. However, there has been no comprehensive evaluation of autoimmune diseases among patients who develop different subtypes of hepatobiliary cancer. We examined the association between autoimmune diseases and cancers of the liver and biliary tract in the Swedish population. METHODS: We analyzed data from national datasets at the Center for Primary Health Care Research (Lund University, Sweden). Data on patients with autoimmune disorders were retrieved from the Swedish Hospital Discharge Register, from 1964 through 2008; 33 diseases were evaluated. Hepatobiliary cancer cases were retrieved from the Swedish Cancer Registry. We calculated standardized incidence ratios (SIRs) and hazard ratios for incident cancers and deaths from hepatobiliary cancers. RESULTS: Among 402,462 patients with autoimmune disorders, 582 were diagnosed with primary liver cancer, 330 with gallbladder cancer, 115 with extrahepatic bile duct cancer, and 43 with ampulla of Vater cancers. We identified 14 autoimmune conditions that were significantly associated with increased risk of primary liver cancer (overall SIR [any autoimmune disease], 2.1; 95% confidence interval [CI], 2.0-2.3), 5 conditions associated with gallbladder cancer (overall SIR, 1.3; 95% CI, 1.1-1.4), and 3 associated with extrahepatic bile duct cancer (overall SIR, 1.6; 95% CI, 1.3-1.9). The autoimmune disorders with the strongest association with primary liver cancer were primary biliary cirrhosis (SIR, 39.5; 95% CI, 28.2-53.8) and autoimmune hepatitis (SIR, 29.0; 95% CI, 9.1-68.2); ulcerative colitis was strongly associated with extrahepatic bile duct cancer (SIR, 5.6; 95% CI, 3.6-8.4). Celiac disease, Crohn's disease, systemic sclerosis, and ulcerative colitis were associated with at least 2 types of cancer. Increased hazard ratios were observed only for patients with biliary tract cancer who had been hospitalized for autoimmune conditions. CONCLUSIONS: In a study of the Swedish population, we identified an increased risk of hepatobiliary cancers among individuals diagnosed with autoimmune disease. Associations among different cancer types indicate that shared immunomodulatory mechanisms determine susceptibility to hepatobiliary cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"stereotactic body radiation therapy cholangiocarcinoma systematic review objective stereotactic body radiation therapy sbrt used treatment cholangiocarcinoma cc toxicity clinical results sbrt cc still limited sparse therefore aim systematic review analyze results sbrt setting advanced cc methods systematic literature search conducted pubmed scopus cochrane library using prisma methodology studies including least 10 patients diagnosis advanced cc regardless tumor site treatments included primary outcome overall survival os secondary endpoints local control lc toxicity rates robins risk bias tool used results 10 studies 231 patients fulfilled selection criteria included review one study showed moderate serious risk bias median follow 15 months range 7 8 64 0 months pooled 1 year os 58 3 95 ci 50 2 66 1 pooled 2 year os 35 5 95 ci 22 1 50 1 pooled 1 year lc 83 4 95 ci 76 5 89 4 reported toxicities acceptable manageable one treatment related death conclusion role sbrt cc yet supported robust evidence literature however within limit preliminary results seem almost comparable ones standard chemotherapy chemoradiation advances knowledge sbrt seems effective terms lc acceptable treatment related toxicities therefore sbrt considered therapeutic option least selected patients cc possibly combined adjuvant chemotherapy cht pubmed","probabilities":0.9799733,"Title":"Stereotactic body radiation therapy in cholangiocarcinoma: a systematic review","Abstract":"OBJECTIVE: Stereotactic body radiation therapy (SBRT) has been used in the treatment of cholangiocarcinoma (CC) but toxicity and clinical results of SBRT in CC are still limited and sparse. Therefore, the aim of this systematic review was to analyze the results of SBRT in the setting of advanced CC. METHODS: A systematic literature search was conducted on PubMed, Scopus, and Cochrane library using the PRISMA methodology. Studies including at least 10 patients with diagnosis of advanced CC regardless of tumor site and other treatments were included. The primary outcome was overall survival (OS) and secondary endpoints were local control (LC) and toxicity rates. The ROBINS-I risk of bias tool was used. RESULTS: 10 studies (231 patients) fulfilled the selection criteria and were included in this review. All but one study showed moderate to serious risk of bias. Median follow up was 15 months (range: 7.8-64.0 months). Pooled 1 year OS was 58.3% ((95%) CI: 50.2-66.1%) and pooled 2 year OS was 35.5% ((95%) CI: 22.1-50.1%). Pooled 1 year LC was 83.4%, ((95%) CI: 76.5-89.4%). The reported toxicities were acceptable and manageable with only one treatment-related death. CONCLUSION: The role of SBRT in CC is not yet supported by robust evidence in literature. However, within this limit, preliminary results seem almost comparable to the ones of standard chemotherapy or chemoradiation. ADVANCES IN KNOWLEDGE: SBRT seems effective in terms of LC with acceptable treatment-related toxicities. Therefore, SBRT can be considered a therapeutic option at least in selected patients with CC, possibly combined with adjuvant chemotherapy (CHT).","Source":"PubMed","category":"HUMAN","training_data":"Stereotactic body radiation therapy in cholangiocarcinoma: a systematic review OBJECTIVE: Stereotactic body radiation therapy (SBRT) has been used in the treatment of cholangiocarcinoma (CC) but toxicity and clinical results of SBRT in CC are still limited and sparse. Therefore, the aim of this systematic review was to analyze the results of SBRT in the setting of advanced CC. METHODS: A systematic literature search was conducted on PubMed, Scopus, and Cochrane library using the PRISMA methodology. Studies including at least 10 patients with diagnosis of advanced CC regardless of tumor site and other treatments were included. The primary outcome was overall survival (OS) and secondary endpoints were local control (LC) and toxicity rates. The ROBINS-I risk of bias tool was used. RESULTS: 10 studies (231 patients) fulfilled the selection criteria and were included in this review. All but one study showed moderate to serious risk of bias. Median follow up was 15 months (range: 7.8-64.0 months). Pooled 1 year OS was 58.3% ((95%) CI: 50.2-66.1%) and pooled 2 year OS was 35.5% ((95%) CI: 22.1-50.1%). Pooled 1 year LC was 83.4%, ((95%) CI: 76.5-89.4%). The reported toxicities were acceptable and manageable with only one treatment-related death. CONCLUSION: The role of SBRT in CC is not yet supported by robust evidence in literature. However, within this limit, preliminary results seem almost comparable to the ones of standard chemotherapy or chemoradiation. ADVANCES IN KNOWLEDGE: SBRT seems effective in terms of LC with acceptable treatment-related toxicities. Therefore, SBRT can be considered a therapeutic option at least in selected patients with CC, possibly combined with adjuvant chemotherapy (CHT). PubMed","prediction_labels":"HUMAN"},{"cleaned":"adjuvant therapy associated improved overall survival patients pancreatobiliary mixed subtype ampullary cancer pancreatoduodenectomy multicenter cohort study background objective benefit adjuvant therapy ampullary cancer ampac patients following pancreatoduodenectomy pd debated aim study determine role adjuvant therapy pancreatoduodenectomy pd histological subtypes ampac methods patients undergoing pd ampac 5 high volume european surgical centers 1996 2017 identified patient baseline characteristics surgical histopathological parameters long term overall survival os resection evaluated results 214 patients undergoing pd ampac included asa score asa1 2 149 vs asa 3 4 82 months median os p 0 002 preoperative serum cea cea 0 5 ng ml 128 vs cea 0 5 ng ml 62 months p 0 013 preoperative serum ca19 9 ca19 9 40 iu ml 147 vs ca19 9 40iu ml 111 months p 0 042 stage t1 2 163 vs t3 4 98 months p 0 001 n stage n0 159 vs n 110 months p 0 001 grading g1 2 145 vs g3 4 113 months p 0 026 r status r0 136 vs r 38 months p 0 031 histological subtype intestinal subtype 156 vs pb m subtype 118 months p 0 003 qualified prognostic parameters multivariable analysis asa score hr 1 784 95 ci 0 997 3 193 p 0 050 n stage hr 1 831 95 ci 0 904 3 707 p 0 033 remained independent prognostic factors pb m subtype ampac patients undergoing adjuvant therapy showed improved median overall survival adjuvant therapy 85 months vs adjuvant therapy 65 months p 0 005 adjuvant therapy remained independent prognostic parameter multivariate analysis hr 0 351 95 ci 0 151 0 851 p 0 015 significant benefit adjuvant therapy intestinal subtype ampac patients conclusion adjuvant treatment seems indicated pancreatobiliary mixed type ampac stn","probabilities":0.9799733,"Title":"Adjuvant Therapy Is Associated With Improved Overall Survival In Patients With Pancreatobiliary Or Mixed Subtype Ampullary Cancer After Pancreatoduodenectomy - A Multicenter Cohort Study","Abstract":"Background/objective: The benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC. \n\n Methods: Patients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated. \n\n Results: 214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3-4 82 months median OS, p = 0.002), preoperative serum CEA (CEA <0.5 ng/ml 128 vs. CEA >0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 < 40 IU/ml 147 vs. CA19-9 > 40IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p < 0.001), N stage (N0 159 vs. N+ 110 months, p < 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997-3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904-3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151-0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients. \n\n Conclusion: Adjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC.","Source":"STN","category":"HUMAN","training_data":"Adjuvant Therapy Is Associated With Improved Overall Survival In Patients With Pancreatobiliary Or Mixed Subtype Ampullary Cancer After Pancreatoduodenectomy - A Multicenter Cohort Study Background/objective: The benefit of adjuvant therapy in ampullary cancer (AMPAC) patients following pancreatoduodenectomy (PD) is debated. The aim of this study was to determine the role of adjuvant therapy after pancreatoduodenectomy (PD) in histological subtypes of AMPAC. \n\n Methods: Patients undergoing PD for AMPAC at 5 high-volume European surgical centers from 1996 to 2017 were identified. Patient baseline characteristics, surgical and histopathological parameters, and long-term overall survival (OS) after resection were evaluated. \n\n Results: 214 patients undergoing PD for AMPAC were included. ASA score (ASA1-2 149 vs. ASA 3-4 82 months median OS, p = 0.002), preoperative serum CEA (CEA <0.5 ng/ml 128 vs. CEA >0.5 ng/ml 62 months, p = 0.013), preoperative serum CA19-9 (CA19-9 < 40 IU/ml 147 vs. CA19-9 > 40IU/ml 111 months, p = 0.042), T stage (T1-2 163 vs. T3-4 98 months, p < 0.001), N stage (N0 159 vs. N+ 110 months, p < 0.001), grading (G1-2 145 vs. G3-4 113 months, p = 0.026), R status (R0 136 vs. R+ 38 months, p = 0.031), and histological subtype (intestinal subtype 156 vs. PB/M subtype 118 months, p = 0.003) qualified as prognostic parameters. In multivariable analysis, ASA score (HR 1.784, 95%CI 0.997-3.193, p = 0.050) and N stage (HR 1.831, 95%CI 0.904-3.707, p = 0.033) remained independent prognostic factors. In PB/M subtype AMPAC, patients undergoing adjuvant therapy showed an improved median overall survival (adjuvant therapy 85 months vs. no adjuvant therapy 65 months, p = 0.005), and adjuvant therapy remained an independent prognostic parameter in multivariate analysis (HR 0.351, 95%CI 0.151-0.851, p = 0.015). There was no significant benefit of adjuvant therapy in intestinal subtype AMPAC patients. \n\n Conclusion: Adjuvant treatment seems indicated in pancreatobiliary or mixed type AMPAC. STN","prediction_labels":"HUMAN"},{"cleaned":"stratification prognosis patients ampullary carcinoma surgery preoperative platelet lymphocyte ratio conventional tumor markers background aim platelet lymphocyte ratio plr recently suggested new predictor prognosis several carcinoma types however clinical impact remains controversial patients ampullary carcinoma thus aim study investigate useful biomarkers identifying poor prognosis patients ampullary carcinoma patients methods forty one patients ampullary carcinoma underwent pancreaticoduodenectomy pd curative resection april 2000 april 2017 various clinicopathological findings patients tumors evaluated potential prognostic factors might enable better stratification prognosis results platelet lymphocyte ratio well markers found prognostic factor patients ampullary carcinoma 2 year disease free survival percentage significantly higher group low plr high plr group 70 2 vs 28 6 p 0 005 combinational analysis plr conventional tms enabled us stratify prognosis patients clearly marker alone conclusion plr useful prognostic factor patients ampullary cancer combination preoperative plr conventional tms markers may powerful predictive factors postoperative prognosis patients ampullary carcinoma following pd stn","probabilities":0.9799733,"Title":"Stratification Of Prognosis In Patients With Ampullary Carcinoma After Surgery By Preoperative Platelet-To-Lymphocyte Ratio And Conventional Tumor Markers","Abstract":"Background/aim: The platelet-to-lymphocyte ratio (PLR) has recently been suggested as a new predictor of the prognosis in several carcinoma types. However, the clinical impact remains controversial in patients with ampullary carcinoma. Thus, the aim of this study was to investigate other useful biomarkers for identifying poor prognosis in patients with ampullary carcinoma. \r\n\r\n Patients and methods: Forty-one patients with ampullary carcinoma underwent pancreaticoduodenectomy (PD) with curative resection between April 2000 and April 2017. Various clinicopathological findings of the patients and their tumors were evaluated as potential prognostic factors which might enable better stratification of prognosis. \r\n\r\n Results: Platelet-to-lymphocyte ratio, as well as other markers, was found to be a prognostic factor in patients with ampullary carcinoma. The 2-year disease-free survival percentage was significantly higher in the group with low PLR than in the high PLR group (70.2% vs. 28.6%; p=0.005). Combinational analysis of the PLR and conventional TMs enabled us to stratify prognosis of the patients more clearly than by each marker alone. \r\n\r\n Conclusion: PLR was a useful prognostic factor for patients with ampullary cancer. The combination of preoperative PLR and conventional TMs markers may be powerful predictive factors for postoperative prognosis in patients with ampullary carcinoma following PD.","Source":"STN","category":"HUMAN","training_data":"Stratification Of Prognosis In Patients With Ampullary Carcinoma After Surgery By Preoperative Platelet-To-Lymphocyte Ratio And Conventional Tumor Markers Background/aim: The platelet-to-lymphocyte ratio (PLR) has recently been suggested as a new predictor of the prognosis in several carcinoma types. However, the clinical impact remains controversial in patients with ampullary carcinoma. Thus, the aim of this study was to investigate other useful biomarkers for identifying poor prognosis in patients with ampullary carcinoma. \r\n\r\n Patients and methods: Forty-one patients with ampullary carcinoma underwent pancreaticoduodenectomy (PD) with curative resection between April 2000 and April 2017. Various clinicopathological findings of the patients and their tumors were evaluated as potential prognostic factors which might enable better stratification of prognosis. \r\n\r\n Results: Platelet-to-lymphocyte ratio, as well as other markers, was found to be a prognostic factor in patients with ampullary carcinoma. The 2-year disease-free survival percentage was significantly higher in the group with low PLR than in the high PLR group (70.2% vs. 28.6%; p=0.005). Combinational analysis of the PLR and conventional TMs enabled us to stratify prognosis of the patients more clearly than by each marker alone. \r\n\r\n Conclusion: PLR was a useful prognostic factor for patients with ampullary cancer. The combination of preoperative PLR and conventional TMs markers may be powerful predictive factors for postoperative prognosis in patients with ampullary carcinoma following PD. STN","prediction_labels":"HUMAN"},{"cleaned":"crenigacestat selective notch1 inhibitor reduces intrahepatic cholangiocarcinoma progression blocking vegfa dll4 mmp13 axis intrahepatic cholangiocarcinoma icca deadly disease rising incidence treatment options altered expression activation notch1 3 receptors shown play role icca development progression study established new cca patient derived xenograft model validated immunohistochemistry transcriptomic analysis effects notch pathway suppression crenigacestat ly3039478 specific inhibitor evaluated human icca cell lines pdx model vitro ly3039478 significantly reduced notch pathway components including nicd1 hes1 notch receptors panel five different icca cell lines pdx model ly3039478 significantly inhibited notch pathway tumor growth extent gemcitabine furthermore gene expression analysis icca mouse tissues treated ly3039478 revealed downregulation vegfa hes1 mmp13 genes tissues dll4 cd31 co localized expression significantly inhibited treated mice happened case mmp13 vitro angiogenesis model ly3039478 inhibited vessel formation restored addition mmp13 finally rna sequencing expression data icca patients matched surrounding normal liver tissues downloaded geo database demonstrated notch1 hes1 mmp13 dll4 vegfa genes significantly upregulated tumors compared adjacent nontumorous tissues data confirmed group using independent cohort icca specimens conclusion developed validated new icca pdx model test vivo activity ly3039478 demonstrating inhibitory role notch dependent angiogenesis thus present data provide new knowledge notch signaling icca support inhibition notch cascade promising strategy treatment disease stn","probabilities":0.9467213,"Title":"Crenigacestat A Selective Notch1 Inhibitor Reduces Intrahepatic Cholangiocarcinoma Progression By Blocking Vegfa/Dll4/Mmp13 Axis","Abstract":"Intrahepatic cholangiocarcinoma (iCCA) is a deadly disease with rising incidence and few treatment options. An altered expression and/or activation of NOTCH1-3 receptors has been shown to play a role in iCCA development and progression. In this study, we established a new CCA patient-derived xenograft model, which was validated by immunohistochemistry and transcriptomic analysis. The effects of Notch pathway suppression by the Crenigacestat (LY3039478)-specific inhibitor were evaluated in human iCCA cell lines and the PDX model. In vitro, LY3039478 significantly reduced Notch pathway components, including NICD1 and HES1, but not the other Notch receptors, in a panel of five different iCCA cell lines. In the PDX model, LY3039478 significantly inhibited the Notch pathway and tumor growth to the same extent as gemcitabine. Furthermore, gene expression analysis of iCCA mouse tissues treated with LY3039478 revealed a downregulation of VEGFA, HES1, and MMP13 genes. In the same tissues, DLL4 and CD31 co-localized, and their expression was significantly inhibited in the treated mice, as it happened in the case of MMP13. In an in vitro angiogenesis model, LY3039478 inhibited vessel formation, which was restored by the addition of MMP13. Finally, RNA-sequencing expression data of iCCA patients and matched surrounding normal liver tissues downloaded from the GEO database demonstrated that NOTCH1, HES1, MMP13, DLL4, and VEGFA genes were significantly upregulated in tumors compared with adjacent nontumorous tissues. These data were confirmed by our group, using an independent cohort of iCCA specimens. Conclusion: We have developed and validated a new iCCA PDX model to test in vivo the activity of LY3039478, demonstrating its inhibitory role in Notch-dependent angiogenesis. Thus, the present data provide new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease.","Source":"STN","category":"ANIMAL","training_data":"Crenigacestat A Selective Notch1 Inhibitor Reduces Intrahepatic Cholangiocarcinoma Progression By Blocking Vegfa/Dll4/Mmp13 Axis Intrahepatic cholangiocarcinoma (iCCA) is a deadly disease with rising incidence and few treatment options. An altered expression and/or activation of NOTCH1-3 receptors has been shown to play a role in iCCA development and progression. In this study, we established a new CCA patient-derived xenograft model, which was validated by immunohistochemistry and transcriptomic analysis. The effects of Notch pathway suppression by the Crenigacestat (LY3039478)-specific inhibitor were evaluated in human iCCA cell lines and the PDX model. In vitro, LY3039478 significantly reduced Notch pathway components, including NICD1 and HES1, but not the other Notch receptors, in a panel of five different iCCA cell lines. In the PDX model, LY3039478 significantly inhibited the Notch pathway and tumor growth to the same extent as gemcitabine. Furthermore, gene expression analysis of iCCA mouse tissues treated with LY3039478 revealed a downregulation of VEGFA, HES1, and MMP13 genes. In the same tissues, DLL4 and CD31 co-localized, and their expression was significantly inhibited in the treated mice, as it happened in the case of MMP13. In an in vitro angiogenesis model, LY3039478 inhibited vessel formation, which was restored by the addition of MMP13. Finally, RNA-sequencing expression data of iCCA patients and matched surrounding normal liver tissues downloaded from the GEO database demonstrated that NOTCH1, HES1, MMP13, DLL4, and VEGFA genes were significantly upregulated in tumors compared with adjacent nontumorous tissues. These data were confirmed by our group, using an independent cohort of iCCA specimens. Conclusion: We have developed and validated a new iCCA PDX model to test in vivo the activity of LY3039478, demonstrating its inhibitory role in Notch-dependent angiogenesis. Thus, the present data provide new knowledge on Notch signaling in iCCA, and support the inhibition of the Notch cascade as a promising strategy for the treatment of this disease. STN","prediction_labels":"ANIMAL"},{"cleaned":"sex specific race ethnicity specific disparities cancer incidence prevalence among adults cholangiocarcinoma us analysis 2000 2011 surveillance epidemiology end results registry aim cholangiocarcinoma cca uncommon lethal malignancy increasing worldwide incidence intrahepatic cholangiocarcinoma icc decreasing incidence extrahepatic cholangiocarcinoma ecc evaluate age specific sex specific race ethnicity specific variations cca incidence usa methods using population based cancer registry data 2000 2011 surveillance epidemiology end results registry retrospectively evaluated age specific sex specific race ethnicity specific variations incidence prevalence cca stratified icc ecc subtypes among adults usa results total 11 296 patients icc 8672 patients ecc identified icc incidence significantly higher ecc incidence 1 6 vs 1 3 per 100 000 year p 0 01 among race ethnic groups among icc ecc asians highest cancer incidence stratified age cca incidence increased age among groups however rising incidence rapid among asians example among patients aged 80 years incidence icc among asians nearly twice incidence among non hispanic whites 13 8 vs 7 2 per 100 000 year overall cca incidence higher among men compared women increasing age sex specific disparity pronounced example among patients aged 80 years incidence icc 9 8 per 100 000 year among men 6 9 per 100 000 year among women conclusion among adults cca usa increasing age associated increasing incidence cca addition sex specific race ethnicity specific disparities seen highest incidence cca among men among asians stn","probabilities":0.9799733,"Title":"Sex-Specific And Race/Ethnicity-Specific Disparities In Cancer Incidence And Prevalence Among Adults With Cholangiocarcinoma In The Us: An Analysis Of The 2000-2011 Surveillance Epidemiology And End Results Registry","Abstract":"Aim: Cholangiocarcinoma (CCA) is an uncommon but lethal malignancy with an increasing worldwide incidence of intrahepatic cholangiocarcinoma (ICC), but decreasing incidence of extrahepatic cholangiocarcinoma (ECC). To evaluate age-specific, sex-specific, race/ethnicity-specific variations in CCA incidence in the USA. \r\n\r\n Methods: Using population-based cancer registry data from the 2000-2011 Surveillance, Epidemiology and End Results registry, we retrospectively evaluated age-specific, sex-specific, race/ethnicity-specific variations in incidence and prevalence of CCA stratified by ICC and ECC subtypes among adults in the USA. \r\n\r\n Results: A total of 11 296 patients with ICC and 8672 patients with ECC were identified. ICC incidence was significantly higher than ECC incidence (1.6 vs 1.3 per 100 000/year, P < 0.01). Among all race/ethnic groups and among both ICC and ECC, Asians had the highest cancer incidence. When stratified by age, CCA incidence increased with age among all groups; however, the rising incidence was most rapid among Asians. For example, among patients aged 80 years and over, the incidence of ICC among Asians was nearly twice the incidence among non-Hispanic whites (13.8 vs 7.2 per 100 000/year). Overall, CCA incidence was higher among men compared with women, and with increasing age, this sex-specific disparity was more pronounced. For example, among patients aged 80 years and over, the incidence of ICC was 9.8 per 100 000/year among men and 6.9 per 100 000/year among women. \r\n\r\n Conclusion: Among adults with CCA in the USA, increasing age was associated with increasing incidence of CCA. In addition, sex-specific and race/ethnicity-specific disparities were seen with the highest incidence of CCA among men and among Asians.","Source":"STN","category":"HUMAN","training_data":"Sex-Specific And Race/Ethnicity-Specific Disparities In Cancer Incidence And Prevalence Among Adults With Cholangiocarcinoma In The Us: An Analysis Of The 2000-2011 Surveillance Epidemiology And End Results Registry Aim: Cholangiocarcinoma (CCA) is an uncommon but lethal malignancy with an increasing worldwide incidence of intrahepatic cholangiocarcinoma (ICC), but decreasing incidence of extrahepatic cholangiocarcinoma (ECC). To evaluate age-specific, sex-specific, race/ethnicity-specific variations in CCA incidence in the USA. \r\n\r\n Methods: Using population-based cancer registry data from the 2000-2011 Surveillance, Epidemiology and End Results registry, we retrospectively evaluated age-specific, sex-specific, race/ethnicity-specific variations in incidence and prevalence of CCA stratified by ICC and ECC subtypes among adults in the USA. \r\n\r\n Results: A total of 11 296 patients with ICC and 8672 patients with ECC were identified. ICC incidence was significantly higher than ECC incidence (1.6 vs 1.3 per 100 000/year, P < 0.01). Among all race/ethnic groups and among both ICC and ECC, Asians had the highest cancer incidence. When stratified by age, CCA incidence increased with age among all groups; however, the rising incidence was most rapid among Asians. For example, among patients aged 80 years and over, the incidence of ICC among Asians was nearly twice the incidence among non-Hispanic whites (13.8 vs 7.2 per 100 000/year). Overall, CCA incidence was higher among men compared with women, and with increasing age, this sex-specific disparity was more pronounced. For example, among patients aged 80 years and over, the incidence of ICC was 9.8 per 100 000/year among men and 6.9 per 100 000/year among women. \r\n\r\n Conclusion: Among adults with CCA in the USA, increasing age was associated with increasing incidence of CCA. In addition, sex-specific and race/ethnicity-specific disparities were seen with the highest incidence of CCA among men and among Asians. STN","prediction_labels":"HUMAN"},{"cleaned":"autocrine parathyroid hormone like hormone promotes intrahepatic cholangiocarcinoma cell proliferation via increased erk jnk atf2 cyclind1 signaling background aims intrahepatic cholangiocarcinoma icc aggressive tumor high fatality rate recently found parathyroid hormone like hormone pthlh frequently overexpressed icc compared non tumor tissue study aimed elucidate underlying mechanisms pthlh icc development methods cck 8 assay colony formation assays flow cytometry xenograft model used examine role pthlh icc cells proliferation immunohistochemistry ihc western blot assays used detect target proteins luciferase reporter chromatin immunoprecipitation chip dna pull assays used verify transcription regulation activating transcription factor 2 atf2 results pthlh significantly upregulated icc compared adjacent normal tissues upregulation pthlh indicated poor pathological differentiation intrahepatic metastasis functional study demonstrated pthlh silencing markedly suppressed icc cells growth specific overexpression pthlh opposite effect mechanistically secreted pthlh promote icc cell growth activating extracellular signal related kinase erk c jun n terminal kinase jnk signaling pathways subsequently upregulated atf2 cyclind1 expression study found promoter activity pthlh negatively regulated atf2 indicating negative feedback loop exists conclusions findings demonstrated icc secreted pthlh plays characteristic growth promoting role activating canonical erk jnk atf2 cyclind1 signaling pathways icc development identified negative feedback loop formed atf2 pthlh study explored therapeutic implication icc patients stn","probabilities":0.9467213,"Title":"Autocrine Parathyroid Hormone-Like Hormone Promotes Intrahepatic Cholangiocarcinoma Cell Proliferation Via Increased Erk/Jnk-Atf2-Cyclind1 Signaling","Abstract":"Background and aims: Intrahepatic cholangiocarcinoma (ICC) is an aggressive tumor with a high fatality rate. It was recently found that parathyroid hormone-like hormone (PTHLH) was frequently overexpressed in ICC compared with non-tumor tissue. This study aimed to elucidate the underlying mechanisms of PTHLH in ICC development. \r\n\r\n Methods: The CCK-8 assay, colony formation assays, flow cytometry and a xenograft model were used to examine the role of PTHLH in ICC cells proliferation. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. Luciferase reporter, chromatin immunoprecipitation (ChIP) and DNA pull-down assays were used to verify the transcription regulation of activating transcription factor-2 (ATF2). \r\n\r\n Results: PTHLH was significantly upregulated in ICC compared with adjacent and normal tissues. Upregulation of PTHLH indicated a poor pathological differentiation and intrahepatic metastasis. Functional study demonstrated that PTHLH silencing markedly suppressed ICC cells growth, while specific overexpression of PTHLH has the opposite effect. Mechanistically, secreted PTHLH could promote ICC cell growth by activating extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and subsequently upregulated ATF2 and cyclinD1 expression. Further study found that the promoter activity of PTHLH were negatively regulated by ATF2, indicating that a negative feedback loop exists. \r\n\r\n Conclusions: Our findings demonstrated that the ICC-secreted PTHLH plays a characteristic growth-promoting role through activating the canonical ERK/JNK-ATF2-cyclinD1 signaling pathways in ICC development. We identified a negative feedback loop formed by ATF2 and PTHLH. In this study, we explored the therapeutic implication for ICC patients.","Source":"STN","category":"ANIMAL","training_data":"Autocrine Parathyroid Hormone-Like Hormone Promotes Intrahepatic Cholangiocarcinoma Cell Proliferation Via Increased Erk/Jnk-Atf2-Cyclind1 Signaling Background and aims: Intrahepatic cholangiocarcinoma (ICC) is an aggressive tumor with a high fatality rate. It was recently found that parathyroid hormone-like hormone (PTHLH) was frequently overexpressed in ICC compared with non-tumor tissue. This study aimed to elucidate the underlying mechanisms of PTHLH in ICC development. \r\n\r\n Methods: The CCK-8 assay, colony formation assays, flow cytometry and a xenograft model were used to examine the role of PTHLH in ICC cells proliferation. Immunohistochemistry (IHC) and western blot assays were used to detect target proteins. Luciferase reporter, chromatin immunoprecipitation (ChIP) and DNA pull-down assays were used to verify the transcription regulation of activating transcription factor-2 (ATF2). \r\n\r\n Results: PTHLH was significantly upregulated in ICC compared with adjacent and normal tissues. Upregulation of PTHLH indicated a poor pathological differentiation and intrahepatic metastasis. Functional study demonstrated that PTHLH silencing markedly suppressed ICC cells growth, while specific overexpression of PTHLH has the opposite effect. Mechanistically, secreted PTHLH could promote ICC cell growth by activating extracellular signal-related kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways, and subsequently upregulated ATF2 and cyclinD1 expression. Further study found that the promoter activity of PTHLH were negatively regulated by ATF2, indicating that a negative feedback loop exists. \r\n\r\n Conclusions: Our findings demonstrated that the ICC-secreted PTHLH plays a characteristic growth-promoting role through activating the canonical ERK/JNK-ATF2-cyclinD1 signaling pathways in ICC development. We identified a negative feedback loop formed by ATF2 and PTHLH. In this study, we explored the therapeutic implication for ICC patients. STN","prediction_labels":"ANIMAL"},{"cleaned":"human equilibrative nucleoside transporter 1 expression predicts survival advanced cholangiocarcinoma patients treated gemcitabine based adjuvant chemotherapy surgical resection objective aim study evaluate whether intratumoral human equilibrative nucleoside transporter 1 hent1 expression predict survival advanced cholangiocarcinoma patients treated adjuvant gemcitabine based chemotherapy agc surgical resection background reports concerning useful predictive biomarker patients cholangiocarcinoma treated adjuvant gemcitabine chemotherapy methods intratumoral hent1 expression investigated immunohistochemically 105 patients resected advanced cholangiocarcinoma relationships intratumoral hent1 expression clinicopathological factors evaluated univariate multivariate analyses study retrospective analysis retrospectively collected tissue data results fifty one patients received agc 54 high low intratumoral hent1 expression found 74 70 31 patients 30 respectively significant differences clinicopathological factors patients high hent1 expression low hent1 expression survival patients high hent1 expression significantly better low hent1 expression among patients received agc p 0 008 among patients p 0 894 moreover significant difference survival patients received agc observed among patients high hent1 expression p 0 002 among patients low hent1 expression p 0 525 intratumoral hent1 expression independent predictive factor patients treated agc multivariate analysis p 0 027 conclusions intratumoral hent1 expression may potent predictive marker advanced cholangiocarcinoma patients treated agc pubmed","probabilities":0.8684211,"Title":"Human equilibrative nucleoside transporter 1 expression predicts survival of advanced cholangiocarcinoma patients treated with gemcitabine-based adjuvant chemotherapy after surgical resection","Abstract":"OBJECTIVE: The aim of this study was to evaluate whether intratumoral human equilibrative nucleoside transporter 1 (hENT1) expression can predict the survival of advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. BACKGROUND: There have been no reports concerning a useful predictive biomarker in patients with cholangiocarcinoma treated with adjuvant gemcitabine chemotherapy. METHODS: Intratumoral hENT1 expression was investigated immunohistochemically in 105 patients with resected advanced cholangiocarcinoma. Relationships between intratumoral hENT1 expression and clinicopathological factors were evaluated by univariate and multivariate analyses. This study was a retrospective analysis on retrospectively collected tissue and data. RESULTS: Fifty-one patients received AGC, and 54 did not. High and low intratumoral hENT1 expression was found in 74 (70%) and 31 patients (30%), respectively. There were no significant differences in clinicopathological factors between patients with high hENT1 expression and those with low hENT1 expression. Survival patients with high hENT1 expression were significantly better than those with low hENT1 expression among patients who received AGC (P = 0.008), but not among patients who did not (P = 0.894). Moreover, a significant difference in survival between patients who received AGC and those who did not was observed among patients with high hENT1 expression (P = 0.002), but not among patients with low hENT1 expression (P = 0.525). Intratumoral hENT1 expression was only an independent predictive factor for patients treated with AGC by multivariate analysis (P = 0.027). CONCLUSIONS: Intratumoral hENT1 expression may be a potent predictive marker for advanced cholangiocarcinoma patients treated with AGC.","Source":"PubMed","category":"HUMAN","training_data":"Human equilibrative nucleoside transporter 1 expression predicts survival of advanced cholangiocarcinoma patients treated with gemcitabine-based adjuvant chemotherapy after surgical resection OBJECTIVE: The aim of this study was to evaluate whether intratumoral human equilibrative nucleoside transporter 1 (hENT1) expression can predict the survival of advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. BACKGROUND: There have been no reports concerning a useful predictive biomarker in patients with cholangiocarcinoma treated with adjuvant gemcitabine chemotherapy. METHODS: Intratumoral hENT1 expression was investigated immunohistochemically in 105 patients with resected advanced cholangiocarcinoma. Relationships between intratumoral hENT1 expression and clinicopathological factors were evaluated by univariate and multivariate analyses. This study was a retrospective analysis on retrospectively collected tissue and data. RESULTS: Fifty-one patients received AGC, and 54 did not. High and low intratumoral hENT1 expression was found in 74 (70%) and 31 patients (30%), respectively. There were no significant differences in clinicopathological factors between patients with high hENT1 expression and those with low hENT1 expression. Survival patients with high hENT1 expression were significantly better than those with low hENT1 expression among patients who received AGC (P = 0.008), but not among patients who did not (P = 0.894). Moreover, a significant difference in survival between patients who received AGC and those who did not was observed among patients with high hENT1 expression (P = 0.002), but not among patients with low hENT1 expression (P = 0.525). Intratumoral hENT1 expression was only an independent predictive factor for patients treated with AGC by multivariate analysis (P = 0.027). CONCLUSIONS: Intratumoral hENT1 expression may be a potent predictive marker for advanced cholangiocarcinoma patients treated with AGC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"orotate phosphoribosyltransferase predictor benefit 1 adjuvant chemotherapy cholangiocarcinoma patients background aim improve prognosis cholangiocarcinoma investigated potential biomarkers may enable selection patients postoperative adjuvant chemotherapy likely effective methods cohort retrospective study included 170 surgically resected cholangiocarcinoma patients 26 gemcitabine adjuvant chemotherapy gem group 36 1 adjuvant chemotherapy 1 group 103 receiving adjuvant chemotherapy nc group propensity score matching performed adjust patient backgrounds 36 patients nc group selected immunohistochemistry orotate phosphoribosyltransferase oprt human equilibrative nucleoside transporter 1 hent1 performed determine correlation expression disease free survival dfs results matching backgrounds three groups unbiased significant improvement dfs adjuvant chemotherapy observed whole cohort however among high oprt expression patients dfs gem 1 nc groups 5 years 28 8 53 8 25 5 respectively dfs 1 group significantly longer nc group p 0 034 hand significant differences dfs observed among low oprt expression patients hent1 expression shown predictive value multivariate analysis high oprt expression patients demonstrated 1 adjuvant chemotherapy reduce tumor recurrence hr 0 303 p 0 013 conclusion cholangiocarcinoma patients high oprt expression benefit postoperative adjuvant 1 therapy increases dfs assessment oprt expression may contribute optimization adjuvant chemotherapy cholangiocarcinoma pubmed","probabilities":0.8684211,"Title":"Orotate phosphoribosyltransferase as a predictor of benefit from S-1 adjuvant chemotherapy for cholangiocarcinoma patients","Abstract":"BACKGROUND AND AIM: To improve the prognosis of cholangiocarcinoma, we investigated potential biomarkers that may enable the selection of patients for whom postoperative adjuvant chemotherapy is likely effective. METHODS: The cohort of this retrospective study included 170 surgically resected cholangiocarcinoma patients, 26 with gemcitabine adjuvant chemotherapy (GEM group), 36 with S-1 adjuvant chemotherapy (S-1 group), and 103 receiving no adjuvant chemotherapy (NC group). Propensity score matching was performed to adjust patient backgrounds; 36 patients from the NC group then were selected. Immunohistochemistry of orotate phosphoribosyltransferase (OPRT) and human equilibrative nucleoside transporter 1 (hENT1) was performed to determine the correlation between their expression and disease-free survival (DFS). RESULTS: After matching, the backgrounds of these three groups were unbiased. No significant improvement of DFS by adjuvant chemotherapy was observed in the whole cohort. However, among the high-OPRT-expression patients, DFS of GEM, S-1, and NC groups at 5 years was 28.8%, 53.8%, and 25.5%, respectively. The DFS of the S-1 group was significantly longer than that of the NC group (P = 0.034). On the other hand, no significant differences in DFS were observed among the low OPRT expression patients. hENT1 expression was shown to have no predictive value. Multivariate analysis of the high-OPRT-expression patients demonstrated that S-1 adjuvant chemotherapy can reduce tumor recurrence (HR, 0.303; P = 0.013). CONCLUSION: Cholangiocarcinoma patients with high OPRT expression would benefit from postoperative adjuvant S-1 therapy, which increases the DFS. Assessment of OPRT expression may contribute to the optimization of adjuvant chemotherapy for cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Orotate phosphoribosyltransferase as a predictor of benefit from S-1 adjuvant chemotherapy for cholangiocarcinoma patients BACKGROUND AND AIM: To improve the prognosis of cholangiocarcinoma, we investigated potential biomarkers that may enable the selection of patients for whom postoperative adjuvant chemotherapy is likely effective. METHODS: The cohort of this retrospective study included 170 surgically resected cholangiocarcinoma patients, 26 with gemcitabine adjuvant chemotherapy (GEM group), 36 with S-1 adjuvant chemotherapy (S-1 group), and 103 receiving no adjuvant chemotherapy (NC group). Propensity score matching was performed to adjust patient backgrounds; 36 patients from the NC group then were selected. Immunohistochemistry of orotate phosphoribosyltransferase (OPRT) and human equilibrative nucleoside transporter 1 (hENT1) was performed to determine the correlation between their expression and disease-free survival (DFS). RESULTS: After matching, the backgrounds of these three groups were unbiased. No significant improvement of DFS by adjuvant chemotherapy was observed in the whole cohort. However, among the high-OPRT-expression patients, DFS of GEM, S-1, and NC groups at 5 years was 28.8%, 53.8%, and 25.5%, respectively. The DFS of the S-1 group was significantly longer than that of the NC group (P = 0.034). On the other hand, no significant differences in DFS were observed among the low OPRT expression patients. hENT1 expression was shown to have no predictive value. Multivariate analysis of the high-OPRT-expression patients demonstrated that S-1 adjuvant chemotherapy can reduce tumor recurrence (HR, 0.303; P = 0.013). CONCLUSION: Cholangiocarcinoma patients with high OPRT expression would benefit from postoperative adjuvant S-1 therapy, which increases the DFS. Assessment of OPRT expression may contribute to the optimization of adjuvant chemotherapy for cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"photodynamic therapy may provide benefit systemic chemotherapy among non surgically managed patients extrahepatic cholangiocarcinoma background systemic chemotherapy standard treatment patients unresectable extrahepatic cholangiocarcinoma ecc however survival benefit chemotherapy limited photodynamic therapy pdt associated improved survival among patients advanced ecc yet utilization pdt remains low sought compare outcomes patients unresectable ecc following treatment pdt versus chemotherapy methods review national cancer database conducted identify patients ecc nonsurgically managed 2004 2013 overall survival os patients receiving pdt vs systemic chemotherapy compared using propensity score matching results propensity matching pdt n 59 chemotherapy n 177 5 year os 17 6 95 confidence interval ci 9 0 28 6 among patients underwent pdt vs 3 8 95 ci 0 4 14 0 among patients receiving chemotherapy p 001 multivariable analysis pdt associated os benefit hazard ratio 0 72 95 ci 0 52 0 998 p 048 subset analysis patients receiving pdt n 45 patients receiving chemotherapy demonstrated similar results subset analysis patients undergoing pdt vs pdt chemotherapy os comparable conclusion pdt associated survival benefit compared chemotherapy alone among patients unresectable ecc stn","probabilities":0.9799733,"Title":"Photodynamic Therapy May Provide A Benefit Over Systemic Chemotherapy Among Non-Surgically Managed Patients With Extrahepatic Cholangiocarcinoma","Abstract":"Background: Systemic chemotherapy is the standard treatment for patients with unresectable extrahepatic cholangiocarcinoma (ECC), however, the survival benefit of chemotherapy is limited. Photodynamic therapy (PDT) has been associated with improved survival among patients with advanced ECC, yet utilization of PDT remains low. We sought to compare the outcomes of patients with unresectable ECC following treatment with PDT versus chemotherapy. \r\n\r\n Methods: A review of the National Cancer Database was conducted to identify patients with ECC who were nonsurgically managed between 2004 and 2013. Overall survival (OS) of patients receiving PDT vs systemic chemotherapy was compared using propensity score matching. \r\n\r\n Results: After propensity matching (PDT, n = 59; chemotherapy, n = 177), 5-year OS was 17.6% (95% confidence interval [CI], 9.0%-28.6%) among patients who underwent PDT vs 3.8% (95%CI, 0.4%-14.0%) among patients receiving chemotherapy (P < .001). On multivariable analysis PDT was associated with an OS benefit (hazard ratio, 0.72; 95%CI, 0.52-0.998; P = .048). Subset analysis of patients receiving PDT only (n = 45) and patients receiving chemotherapy demonstrated similar results. In subset analysis of patients undergoing PDT-only vs PDT-chemotherapy, OS was comparable. \r\n\r\n Conclusion: PDT was associated with a survival benefit compared with chemotherapy alone among patients with unresectable ECC.","Source":"STN","category":"HUMAN","training_data":"Photodynamic Therapy May Provide A Benefit Over Systemic Chemotherapy Among Non-Surgically Managed Patients With Extrahepatic Cholangiocarcinoma Background: Systemic chemotherapy is the standard treatment for patients with unresectable extrahepatic cholangiocarcinoma (ECC), however, the survival benefit of chemotherapy is limited. Photodynamic therapy (PDT) has been associated with improved survival among patients with advanced ECC, yet utilization of PDT remains low. We sought to compare the outcomes of patients with unresectable ECC following treatment with PDT versus chemotherapy. \r\n\r\n Methods: A review of the National Cancer Database was conducted to identify patients with ECC who were nonsurgically managed between 2004 and 2013. Overall survival (OS) of patients receiving PDT vs systemic chemotherapy was compared using propensity score matching. \r\n\r\n Results: After propensity matching (PDT, n = 59; chemotherapy, n = 177), 5-year OS was 17.6% (95% confidence interval [CI], 9.0%-28.6%) among patients who underwent PDT vs 3.8% (95%CI, 0.4%-14.0%) among patients receiving chemotherapy (P < .001). On multivariable analysis PDT was associated with an OS benefit (hazard ratio, 0.72; 95%CI, 0.52-0.998; P = .048). Subset analysis of patients receiving PDT only (n = 45) and patients receiving chemotherapy demonstrated similar results. In subset analysis of patients undergoing PDT-only vs PDT-chemotherapy, OS was comparable. \r\n\r\n Conclusion: PDT was associated with a survival benefit compared with chemotherapy alone among patients with unresectable ECC. STN","prediction_labels":"HUMAN"},{"cleaned":"extended liver resections intrahepatic cholangiocarcinoma friend foe background patients intrahepatic cholangiocarcinoma icc extended liver resections elrs increase rate resectability aims present study evaluate morbidity oncologic outcomes elr compared liver resections lr icc methods lr icc performed center january 1997 september 2013 conducted curative intent included retrospective analysis elrs defined resections 5 liver segments factors influenced occurrence major complications clavien 3 overall survival os tested univariate multivariate analyses results one hundred seven patients 82 men 25 women resected 27 25 3 underwent elrs compared lrs elrs performed larger tumors p 003 significantly associated complex surgeries vascular p 001 biliary reconstructions p 001 multivariate analysis revealed elr independent risk factor major complications odds ratio 6 2 95 ci 2 11 19 62 p 001 compared lrs elrs effects os disease free survival p 881 p 228 respectively perioperative blood transfusion hazard ratio hr 2 51 95 ci 1 49 4 23 p 001 presence 1 nodule hr 3 17 95 ci 1 67 5 97 p 001 age 65 years hr 1 72 95 ci 1 03 2 86 p 036 independent prognostic factors os conclusion study suggests elrs performed large iccs affect negatively oncologic outcomes despite increased risk major complications pubmed","probabilities":0.9799733,"Title":"Extended liver resections for intrahepatic cholangiocarcinoma: friend or foe?","Abstract":"BACKGROUND: In patients with intrahepatic cholangiocarcinoma (ICC), extended liver resections (ELRs) increase the rate of resectability. The aims of the present study were to evaluate the morbidity and oncologic outcomes of ELR compared with other liver resections (LR) for ICC. METHODS: All LR for ICC that were performed in our center between January 1997 and September 2013 and conducted with curative intent were included in this retrospective analysis. ELRs were defined by resections of ≥5 liver segments. The factors that influenced the occurrence of major complications (Clavien ≥ 3) and overall survival (OS) were tested with univariate and multivariate analyses. RESULTS: One hundred seven patients (82 men and 25 women) were resected, and 27 (25.3%) underwent ELRs. Compared with the LRs, the ELRs were performed in larger tumors (P = .003) and were significantly associated with more complex surgeries such as vascular (P < .001) or biliary reconstructions (P < .001). Multivariate analysis revealed that ELR was an independent risk factor for major complications (odds ratio [OR], 6.2; 95% CI, 2.11-19.62; P < .001). Compared with the other LRs, ELRs had no effects on OS or disease-free survival (P = .881 and P = .228, respectively). Perioperative blood transfusion (Hazard ratio (HR), 2.51; 95% CI, 1.49-4.23; P < .001), the presence of >1 nodule (HR, 3.17; 95% CI, 1.67-5.97; P < .001), and age ≥65 years (HR, 1.72; 95% CI, 1.03-2.86; P = .036) were independent prognostic factors for OS. CONCLUSION: This study suggests that ELRs performed for large ICCs do not affect negatively oncologic outcomes, despite the increased risk of major complications.","Source":"PubMed","category":"HUMAN","training_data":"Extended liver resections for intrahepatic cholangiocarcinoma: friend or foe? BACKGROUND: In patients with intrahepatic cholangiocarcinoma (ICC), extended liver resections (ELRs) increase the rate of resectability. The aims of the present study were to evaluate the morbidity and oncologic outcomes of ELR compared with other liver resections (LR) for ICC. METHODS: All LR for ICC that were performed in our center between January 1997 and September 2013 and conducted with curative intent were included in this retrospective analysis. ELRs were defined by resections of ≥5 liver segments. The factors that influenced the occurrence of major complications (Clavien ≥ 3) and overall survival (OS) were tested with univariate and multivariate analyses. RESULTS: One hundred seven patients (82 men and 25 women) were resected, and 27 (25.3%) underwent ELRs. Compared with the LRs, the ELRs were performed in larger tumors (P = .003) and were significantly associated with more complex surgeries such as vascular (P < .001) or biliary reconstructions (P < .001). Multivariate analysis revealed that ELR was an independent risk factor for major complications (odds ratio [OR], 6.2; 95% CI, 2.11-19.62; P < .001). Compared with the other LRs, ELRs had no effects on OS or disease-free survival (P = .881 and P = .228, respectively). Perioperative blood transfusion (Hazard ratio (HR), 2.51; 95% CI, 1.49-4.23; P < .001), the presence of >1 nodule (HR, 3.17; 95% CI, 1.67-5.97; P < .001), and age ≥65 years (HR, 1.72; 95% CI, 1.03-2.86; P = .036) were independent prognostic factors for OS. CONCLUSION: This study suggests that ELRs performed for large ICCs do not affect negatively oncologic outcomes, despite the increased risk of major complications. PubMed","prediction_labels":"HUMAN"},{"cleaned":"world wide incidence biliary tract cancer btc background existing epidemiologic research btc limited certain subtypes eg gallbladder cancer gbc combines btc liver cancer reports regional statistics main sources global btc epidemiology particularly anatomic sites literature reviews subject limitations like inconsistent classification subtypes varying standard population adjustment comparison timeframes given increasing incidence btc critical monitor global epidemiology provide insight public health management clinical program development methods evaluated btc incidence 15 countries using cancer incidence five continents database volume xi ci5 xi international agency research cancer ci5 xi registries cover data 2008 12 variations incidence examined country region anatomic site extrahepatic cholangiocarcinoma ecc intrahepatic cholangiocarcinoma icc gbc ampulla vater cancer avc unspecified btcs incidence adjusted standard world population reported age standardized rate asr per 100 000 person years standard error se results highest incidence total btc south korea sk asr 3 00 se 0 02 lowest uk asr 0 66 se 0 01 overall btc incidence higher asian countries western asian americans general us population asr 1 00 se 0 02 0 77 se 0 01 respectively thailand btc incidence higher north south asr 1 93 se 0 05 1 05 se 0 03 respectively gbc ecc top common subtypes countries reported sk highest incidence subtypes asr 2 gbc ecc icc outside sk gbc ecc common japan asr 1 93 se 0 02 2 66 se 0 03 respectively icc common thailand asr 1 73 se 0 05 high france asr 1 01 se 0 03 conclusions registry data support past reports higher btc incidence asian vs western countries well regional variation within countries data also suggests high btc rates asian populations may entirely geographical asian americans suffer higher btc incidence overall us population google scholar","probabilities":0.9799733,"Title":"The World-Wide Incidence Of Biliary Tract Cancer (Btc)","Abstract":"Background: Existing epidemiologic research for BTC is limited to certain subtypes, eg gallbladder cancer (GBC), or combines BTC with liver cancer, and only reports regional statistics. Main sources for global BTC epidemiology (particularly anatomic sites) are literature reviews, which can be subject to limitations like inconsistent classification of subtypes, and varying standard population adjustment and comparison timeframes. Given the increasing incidence of BTC, it is critical to monitor global epidemiology to provide insight to public health management and clinical program development. Methods: We evaluated BTC incidence in 15 countries using the Cancer Incidence in Five Continents database Volume XI (CI5 XI) from the International Agency for Research on Cancer. Most CI5 XI registries cover data from 2008-12 with some variations. Incidence was examined by country, region, and anatomic site (extrahepatic cholangiocarcinoma, ECC; intrahepatic cholangiocarcinoma, ICC; GBC; ampulla of Vater cancer, AVC; and unspecified BTCs). Incidence was adjusted to standard world population and reported as age-standardized rate (ASR; per 100,000 person-years) with standard error (SE). Results: The highest incidence of total BTC was in South Korea (SK; ASR = 3.00, SE = 0.02) and lowest in the UK (ASR = 0.66, SE = 0.01). Overall, BTC incidence was higher in Asian countries than Western, and in Asian-Americans than the general US population (ASR = 1.00, SE = 0.02 and 0.77, SE > 0.01, respectively). In Thailand, BTC incidence was higher in the North than South (ASR = 1.93, SE = 0.05 and 1.05, SE = 0.03, respectively). GBC and ECC are the top common subtypes in most countries reported. SK had the highest incidence of all subtypes, with ASR > 2 in GBC, ECC, and ICC. Outside of SK, GBC and ECC were most common in Japan (ASR = 1.93, SE = 0.02 and 2.66, SE = 0.03, respectively); ICC was most common in Thailand (ASR = 1.73, SE = 0.05) and high in France (ASR = 1.01, SE = 0.03). Conclusions: These registry data support past reports of higher BTC incidence in Asian vs Western countries as well as regional variation within countries. Data also suggests that high BTC rates in Asian populations may not be entirely geographical as Asian-Americans suffer a higher BTC incidence than the overall US population.","Source":"Google Scholar","category":"HUMAN","training_data":"The World-Wide Incidence Of Biliary Tract Cancer (Btc) Background: Existing epidemiologic research for BTC is limited to certain subtypes, eg gallbladder cancer (GBC), or combines BTC with liver cancer, and only reports regional statistics. Main sources for global BTC epidemiology (particularly anatomic sites) are literature reviews, which can be subject to limitations like inconsistent classification of subtypes, and varying standard population adjustment and comparison timeframes. Given the increasing incidence of BTC, it is critical to monitor global epidemiology to provide insight to public health management and clinical program development. Methods: We evaluated BTC incidence in 15 countries using the Cancer Incidence in Five Continents database Volume XI (CI5 XI) from the International Agency for Research on Cancer. Most CI5 XI registries cover data from 2008-12 with some variations. Incidence was examined by country, region, and anatomic site (extrahepatic cholangiocarcinoma, ECC; intrahepatic cholangiocarcinoma, ICC; GBC; ampulla of Vater cancer, AVC; and unspecified BTCs). Incidence was adjusted to standard world population and reported as age-standardized rate (ASR; per 100,000 person-years) with standard error (SE). Results: The highest incidence of total BTC was in South Korea (SK; ASR = 3.00, SE = 0.02) and lowest in the UK (ASR = 0.66, SE = 0.01). Overall, BTC incidence was higher in Asian countries than Western, and in Asian-Americans than the general US population (ASR = 1.00, SE = 0.02 and 0.77, SE > 0.01, respectively). In Thailand, BTC incidence was higher in the North than South (ASR = 1.93, SE = 0.05 and 1.05, SE = 0.03, respectively). GBC and ECC are the top common subtypes in most countries reported. SK had the highest incidence of all subtypes, with ASR > 2 in GBC, ECC, and ICC. Outside of SK, GBC and ECC were most common in Japan (ASR = 1.93, SE = 0.02 and 2.66, SE = 0.03, respectively); ICC was most common in Thailand (ASR = 1.73, SE = 0.05) and high in France (ASR = 1.01, SE = 0.03). Conclusions: These registry data support past reports of higher BTC incidence in Asian vs Western countries as well as regional variation within countries. Data also suggests that high BTC rates in Asian populations may not be entirely geographical as Asian-Americans suffer a higher BTC incidence than the overall US population. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"potent vitro vivo antitumor activity sorafenib human intrahepatic cholangiocarcinoma cells background intrahepatic cholangiocarcinoma icc rising clinical importance due increasing incidence worldwide poor prognosis suboptimal response therapies new effective therapeutic approaches needed improvement treatment outcome recent study showed sorafenib multikinase inhibitor acts predominantly inhibition raf kinase vascular endothelial growth factor vegf platelet derived growth factor pdgf receptors exhibited potent antitumor activity preclinical model cholangiocarcinoma cells method tested vitro vivo antitumor activity sorafenib human icc cell lines results treatment icc cells sorafenib resulted inhibition proliferation induction apoptosis cell lines cells treated sorafenib phosphorylation mitogen activated protein kinase kinase mek mitogen activated protein kinase mapk also interleukin 6 induced phosphorylation signal transducer activator transcription 3 stat3 inhibited dose dependent manner regulation anti apoptotic protein myeloid cell leukemia 1 mcl 1 paralleled reduced phosphorylation stat3 however sorafenib induced significant change cell cycle distribution expression levels cyclin d1 p27 kip1 cells vivo antitumor activity oral administration sorafenib significantly inhibited growth subcutaneous tumors established immunodeficient mice doses 10 30 100 mg kg moreover administration sorafenib 30 mg kg animals peritoneally disseminated icc resulted significantly prolonged survival compared untreated animals 76 vs 43 days treated vehicle treated mice respectively conclusion results indicate sorafenib potent agent may provide new therapeutic option human icc stn","probabilities":0.9467213,"Title":"Potent In Vitro And In Vivo Antitumor Activity Of Sorafenib Against Human Intrahepatic Cholangiocarcinoma Cells","Abstract":"Background: Intrahepatic cholangiocarcinoma (ICC) is rising in clinical importance due to the increasing incidence worldwide, poor prognosis, and suboptimal response to therapies. New effective therapeutic approaches are needed for improvement of treatment outcome. A recent study showed that sorafenib, a multikinase inhibitor that acts predominantly through inhibition of Raf kinase and vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, exhibited potent antitumor activity in a preclinical model of cholangiocarcinoma cells. \r\n\r\n Method: We tested the in vitro and in vivo antitumor activity of sorafenib against human ICC cell lines. \r\n\r\n Results: Treatment of ICC cells with sorafenib resulted in inhibition of proliferation and induction of apoptosis in the cell lines. In the cells treated with sorafenib, phosphorylation of mitogen-activated protein kinase kinase (MEK) and mitogen-activated protein kinase (MAPK) and also interleukin-6-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) were inhibited in a dose-dependent manner. Down-regulation of the anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) paralleled the reduced phosphorylation of STAT3. However, sorafenib induced no significant change in the cell cycle distribution and the expression levels of cyclin D1 and p27(Kip1) in the cells. For the in vivo antitumor activity, oral administration of sorafenib significantly inhibited the growth of subcutaneous tumors established in immunodeficient mice at doses of 10, 30, and 100 mg/kg. Moreover, administration of sorafenib (30 mg/kg) to animals with peritoneally disseminated ICC resulted in significantly prolonged survival compared with that of untreated animals (76 vs. 43 days in treated and vehicle-treated mice, respectively). \r\n\r\n Conclusion: These results indicate that sorafenib is a potent agent that may provide a new therapeutic option for human ICC.","Source":"STN","category":"ANIMAL","training_data":"Potent In Vitro And In Vivo Antitumor Activity Of Sorafenib Against Human Intrahepatic Cholangiocarcinoma Cells Background: Intrahepatic cholangiocarcinoma (ICC) is rising in clinical importance due to the increasing incidence worldwide, poor prognosis, and suboptimal response to therapies. New effective therapeutic approaches are needed for improvement of treatment outcome. A recent study showed that sorafenib, a multikinase inhibitor that acts predominantly through inhibition of Raf kinase and vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) receptors, exhibited potent antitumor activity in a preclinical model of cholangiocarcinoma cells. \r\n\r\n Method: We tested the in vitro and in vivo antitumor activity of sorafenib against human ICC cell lines. \r\n\r\n Results: Treatment of ICC cells with sorafenib resulted in inhibition of proliferation and induction of apoptosis in the cell lines. In the cells treated with sorafenib, phosphorylation of mitogen-activated protein kinase kinase (MEK) and mitogen-activated protein kinase (MAPK) and also interleukin-6-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3) were inhibited in a dose-dependent manner. Down-regulation of the anti-apoptotic protein myeloid cell leukemia-1 (Mcl-1) paralleled the reduced phosphorylation of STAT3. However, sorafenib induced no significant change in the cell cycle distribution and the expression levels of cyclin D1 and p27(Kip1) in the cells. For the in vivo antitumor activity, oral administration of sorafenib significantly inhibited the growth of subcutaneous tumors established in immunodeficient mice at doses of 10, 30, and 100 mg/kg. Moreover, administration of sorafenib (30 mg/kg) to animals with peritoneally disseminated ICC resulted in significantly prolonged survival compared with that of untreated animals (76 vs. 43 days in treated and vehicle-treated mice, respectively). \r\n\r\n Conclusion: These results indicate that sorafenib is a potent agent that may provide a new therapeutic option for human ICC. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic factors survival patients advanced intrahepatic cholangiocarcinoma treated gemcitabine plus cisplatin first line treatment objectives intrahepatic cholangiocarcinoma icc rare type liver cancer clinically useful prognostic factors reported patients advanced icc present study aimed evaluate clinical prognostic factors patients advanced icc receiving gemcitabine plus cisplatin combination therapy gc standard first line chemotherapy methods retrospective analysis performed data patients icc treated institution march 2011 january 2016 used cox regression model estimated hazard ratios potential prognostic factors survival results 216 patients biliary tract cancer receiving gc first line chemotherapy extracted data 77 patients diagnosed icc received gc first line chemotherapy median overall survival 13 8 months 95 ci 8 9 18 6 multivariate analysis pretreatment serum lactate dehydrogenase hazard ratio hr 2 53 p 0 005 c reactive protein hr 3 06 p 0 001 carcinoembryonic antigen hr 2 39 p 0 03 levels significantly associated overall survival conclusions readily available clinical laboratory values reliably predicted prognosis icc patients receiving gc therapy validated studies results may provide useful tool individual patient risk evaluation design interpretation future trials pubmed","probabilities":0.9799733,"Title":"Prognostic Factors for Survival in Patients with Advanced Intrahepatic Cholangiocarcinoma Treated with Gemcitabine plus Cisplatin as First-Line Treatment","Abstract":"OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. METHODS: A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. RESULTS: Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. CONCLUSIONS: Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Factors for Survival in Patients with Advanced Intrahepatic Cholangiocarcinoma Treated with Gemcitabine plus Cisplatin as First-Line Treatment OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. METHODS: A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. RESULTS: Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. CONCLUSIONS: Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials. PubMed","prediction_labels":"HUMAN"},{"cleaned":"dna methyltransferase inhibitor zebularine induces human cholangiocarcinoma cell death alteration dna methylation status cholangiocarcinoma cca cancer arising neoplastic transformation cholangiocytes tumorigenesis tumor suppressor cancer related genes commonly silenced aberrant dna methylation promoter regions zebularine 1 d ribofuranosyl 1 2 dihydropyrimidin 2 one acts inhibitor dna methylation exhibits chemical stability minimal cytotoxicity vitro vivo study explore effect possible mechanism action zebularine cca cells demonstrate zebularine exerts antitumor effect cca cells zebularine treatment decreased concentrations dna methyltransferase dnmt proteins dnmt1 knockdown led apoptotic cell death cca cell lines tfk 1 hucct1 dna methylation analysis demonstrated zebularine induced dna demethylation go biological process terms hemophilic cell adhesion regulation transcription dna dependent wnt signaling pathway found significantly enriched association demethylated genes furthermore observed zebularine treatment decreased catenin protein levels tfk 1 hucct1 cells results suggest zebularine alters dna methylation status aspect dna demethylation zebularine induces suppression wnt signaling pathway leads apoptotic cell death cca previously reported novel mechanism zebularine induced cell growth arrest apoptosis hepatocellular carcinoma via dna methylation independent pathway together present previous studies indicate zebularine function dnmt inhibitor non dnmt inhibitor reagent optimal usage zebularine may depend cancer type zebularine may useful chemotherapy cancer stn","probabilities":0.9467213,"Title":"Dna Methyltransferase Inhibitor Zebularine Induces Human Cholangiocarcinoma Cell Death Through Alteration Of Dna Methylation Status","Abstract":"Cholangiocarcinoma (CCA) is a cancer arising from the neoplastic transformation of cholangiocytes. During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. In this study, we explore the effect and possible mechanism of action of zebularine on CCA cells. We demonstrate that zebularine exerts an antitumor effect on CCA cells. Zebularine treatment decreased the concentrations of DNA methyltransferase (DNMT) proteins, and DNMT1 knockdown led to apoptotic cell death in the CCA cell lines TFK-1 and HuCCT1. DNA methylation analysis demonstrated that zebularine induced DNA demethylation, and the GO Biological Process terms \"hemophilic cell adhesion\", \"regulation of transcription, DNA-dependent\" and \"Wnt signaling pathway\" were found to be significantly enriched in association with demethylated genes. Furthermore, we observed that zebularine treatment decreased β-catenin protein levels in TFK-1 and HuCCT1 cells. These results suggest that zebularine alters DNA methylation status, and that some aspect of DNA demethylation by zebularine induces suppression of the Wnt signaling pathway, which leads to apoptotic cell death in CCA. We previously reported a novel mechanism of zebularine-induced cell growth arrest and apoptosis in hepatocellular carcinoma via a DNA methylation-independent pathway. Together, our present and previous studies indicate that zebularine could function as both a DNMT inhibitor and a non-DNMT inhibitor reagent, and that, while the optimal usage of zebularine may depend on cancer type, zebularine may be useful for chemotherapy against cancer.","Source":"STN","category":"ANIMAL","training_data":"Dna Methyltransferase Inhibitor Zebularine Induces Human Cholangiocarcinoma Cell Death Through Alteration Of Dna Methylation Status Cholangiocarcinoma (CCA) is a cancer arising from the neoplastic transformation of cholangiocytes. During tumorigenesis, tumor suppressor and cancer-related genes are commonly silenced by aberrant DNA methylation in their promoter regions. Zebularine (1-(β-D-ribofuranosyl)-1,2-dihydropyrimidin-2-one) acts as an inhibitor of DNA methylation and exhibits chemical stability and minimal cytotoxicity both in vitro and in vivo. In this study, we explore the effect and possible mechanism of action of zebularine on CCA cells. We demonstrate that zebularine exerts an antitumor effect on CCA cells. Zebularine treatment decreased the concentrations of DNA methyltransferase (DNMT) proteins, and DNMT1 knockdown led to apoptotic cell death in the CCA cell lines TFK-1 and HuCCT1. DNA methylation analysis demonstrated that zebularine induced DNA demethylation, and the GO Biological Process terms \"hemophilic cell adhesion\", \"regulation of transcription, DNA-dependent\" and \"Wnt signaling pathway\" were found to be significantly enriched in association with demethylated genes. Furthermore, we observed that zebularine treatment decreased β-catenin protein levels in TFK-1 and HuCCT1 cells. These results suggest that zebularine alters DNA methylation status, and that some aspect of DNA demethylation by zebularine induces suppression of the Wnt signaling pathway, which leads to apoptotic cell death in CCA. We previously reported a novel mechanism of zebularine-induced cell growth arrest and apoptosis in hepatocellular carcinoma via a DNA methylation-independent pathway. Together, our present and previous studies indicate that zebularine could function as both a DNMT inhibitor and a non-DNMT inhibitor reagent, and that, while the optimal usage of zebularine may depend on cancer type, zebularine may be useful for chemotherapy against cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"potential biomarkers gallbladder cancer present status future directions context carcinoma gallbladder gbc common biliary tree cancer world beside gallstones specific risk factors gbc currently established several published studies identified various prognostic gene expression markers gbc objective present article reviewed published studies gene expression biomarkers gallbladder cancer susceptibility methods searched pubmed medline embase databases using search terms gallbladder cancer carcinoma expression genes proteins biomarker updated june 2012 limited english language papers online searching accompanied checking reference lists identified articles potentially eligible original reports results potential gbc biomarkers identified different studies summarized conclusion infer present article highlights potential biomarkers gbc however none markers identified far effective routine screening test gbc pubmed","probabilities":0.9799733,"Title":"Potential biomarkers in gallbladder cancer: present status and future directions","Abstract":"CONTEXT: Carcinoma of the gallbladder (GBC) is the most common biliary tree cancer in the world. Beside gallstones, no specific risk factors for GBC are currently established. Several published studies have identified various prognostic gene expression markers in GBC. OBJECTIVE: The present article reviewed published studies on gene expression biomarkers and gallbladder cancer susceptibility. METHODS: We searched the PubMed, Medline, and Embase databases using the search terms \"Gallbladder\", \"cancer/carcinoma\", \"expression\", \"genes\", \"proteins\", and \"biomarker\" updated until June 2012 and limited to English language papers. The online searching was accompanied by checking reference lists from the identified articles for potentially eligible original reports. RESULTS: Potential GBC biomarkers identified by different studies were summarized. CONCLUSION: To infer, the present article highlights a few potential biomarkers in GBC. However, none of the markers identified so far are effective as a routine screening test in GBC.","Source":"PubMed","category":"HUMAN","training_data":"Potential biomarkers in gallbladder cancer: present status and future directions CONTEXT: Carcinoma of the gallbladder (GBC) is the most common biliary tree cancer in the world. Beside gallstones, no specific risk factors for GBC are currently established. Several published studies have identified various prognostic gene expression markers in GBC. OBJECTIVE: The present article reviewed published studies on gene expression biomarkers and gallbladder cancer susceptibility. METHODS: We searched the PubMed, Medline, and Embase databases using the search terms \"Gallbladder\", \"cancer/carcinoma\", \"expression\", \"genes\", \"proteins\", and \"biomarker\" updated until June 2012 and limited to English language papers. The online searching was accompanied by checking reference lists from the identified articles for potentially eligible original reports. RESULTS: Potential GBC biomarkers identified by different studies were summarized. CONCLUSION: To infer, the present article highlights a few potential biomarkers in GBC. However, none of the markers identified so far are effective as a routine screening test in GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pre therapeutic factors predicting survival radioembolization single center experience 389 patients purpose determine pre therapeutic predictive factors overall survival os yttrium y 90 radioembolization re methods retrospectively analyzed pre therapeutic characteristics sex age tumor entity hepatic tumor burden extrahepatic disease ehd liver function focus bilirubin cholinesterase level 389 consecutive patients various refractory liver dominant tumors hepatocellular carcinoma hcc cholangiocarcinoma ccc neuroendocrine tumor net colorectal cancer crc metastatic breast cancer mbc received y 90 radioembolization predicting survival predictive factors selected univariate cox regression analysis subsequently tested multivariate analysis predicting patient survival results median os 356 days 95 ci 285 427 days stable disease observed 132 patients objective response 71 one complete remission progressive disease 122 best survival rate observed patients net worst patients mbc univariate analyses extrahepatic disease p 0 001 large tumor burden p 0 001 high bilirubin levels 1 9 mg dl p 0 001 low cholinesterase levels che 4 62 u p 0 001 baseline significantly associated poor survival tumor entity tumor burden extrahepatic disease che confirmed multivariate analysis independent predictors survival sex applied re dose age significant influence os conclusions pre therapeutic baseline bilirubin che levels extrahepatic disease hepatic tumor burden associated patient survival re parameters may used improve patient selection re primary metastatic liver tumors pubmed","probabilities":0.9799733,"Title":"Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients","Abstract":"PURPOSE: To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). METHODS: We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. RESULTS: The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. CONCLUSIONS: Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors.","Source":"PubMed","category":"HUMAN","training_data":"Pre-therapeutic factors for predicting survival after radioembolization: a single-center experience in 389 patients PURPOSE: To determine pre-therapeutic predictive factors for overall survival (OS) after yttrium (Y)-90 radioembolization (RE). METHODS: We retrospectively analyzed the pre-therapeutic characteristics (sex, age, tumor entity, hepatic tumor burden, extrahepatic disease [EHD] and liver function [with focus on bilirubin and cholinesterase level]) of 389 consecutive patients with various refractory liver-dominant tumors (hepatocellular carcinoma [HCC], cholangiocarcinoma [CCC], neuroendocrine tumor [NET], colorectal cancer [CRC] and metastatic breast cancer [MBC]), who received Y-90 radioembolization for predicting survival. Predictive factors were selected by univariate Cox regression analysis and subsequently tested by multivariate analysis for predicting patient survival. RESULTS: The median OS was 356 days (95% CI 285-427 days). Stable disease was observed in 132 patients, an objective response in 71 (one of which was complete remission) and progressive disease in 122. The best survival rate was observed in patients with NET, and the worst in patients with MBC. In the univariate analyses, extrahepatic disease (P < 0.001), large tumor burden (P = 0.001), high bilirubin levels (>1.9 mg/dL, P < 0.001) and low cholinesterase levels (CHE <4.62 U/I, P < 0.001) at baseline were significantly associated with poor survival. Tumor entity, tumor burden, extrahepatic disease and CHE were confirmed in the multivariate analysis as independent predictors of survival. Sex, applied RE dose and age had no significant influence on OS. CONCLUSIONS: Pre-therapeutic baseline bilirubin and CHE levels, extrahepatic disease and hepatic tumor burden are associated with patient survival after RE. Such parameters may be used to improve patient selection for RE of primary or metastatic liver tumors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"allogeneic blood transfusion affect outcome curative resection advanced cholangiocarcinoma purpose assess impact perioperative blood transfusion overall disease free survival patients undergoing curative resection cholangiocarcinoma methods single center study 128 patients undergoing curative resection cholangiocarcinoma 2001 2010 assessed median follow period 19 months transfused nontransfused patients compared cox regression propensity score analyses results overall 38 patients 29 7 received blood transfusions patient characteristics highly biased respect receiving transfusions propensity score 0 69 0 22 vs 0 11 0 16 p 0 001 unadjusted analysis blood transfusion associated 105 increased risk mortality hazard ratio hr 2 05 95 ci 1 19 3 51 p 0 010 multivariate hr 1 14 95 ci 0 52 2 48 p 0 745 propensity score adjusted cox regression hr 1 02 95 ci 0 39 2 62 p 0 974 blood transfusion influence overall survival similarly propensity score adjusted cox regression hr 0 62 95 ci 0 24 1 58 p 0 295 relevant effect blood transfusion disease free survival observed conclusions knowledge first propensity score based analysis providing compelling evidence worse oncological outcome curative resection advanced cholangiocarcinoma patients receiving perioperative blood transfusions caused clinical circumstances requiring transfusions blood transfusions stn","probabilities":0.9799733,"Title":"Allogeneic Blood Transfusion Does Not Affect Outcome After Curative Resection For Advanced Cholangiocarcinoma","Abstract":"Purpose: To assess the impact of perioperative blood transfusion on overall and disease-free survival in patients undergoing curative resection for cholangiocarcinoma. \r\n\r\n Methods: In a single-center study, 128 patients undergoing curative resection for cholangiocarcinoma between 2001 and 2010 were assessed. The median follow-up period was 19 months. Transfused and nontransfused patients were compared by Cox regression and propensity score analyses. \r\n\r\n Results: Overall, 38 patients (29.7 %) received blood transfusions. The patient characteristics were highly biased with respect to receiving transfusions (propensity score 0.69 ± 0.22 vs. 0.11 ± 0.16, p < 0.001). In the unadjusted analysis, blood transfusion was associated with a 105 % increased risk of mortality [hazard ratio (HR) 2.05, 95 % CI 1.19-3.51, p = 0.010]. In the multivariate (HR 1.14, 95 % CI 0.52-2.48, p = 0.745) and the propensity score-adjusted Cox regression (HR 1.02, 95 % CI 0.39-2.62, p = 0.974), blood transfusion had no influence on overall survival. Similarly, in the propensity score-adjusted Cox regression (HR 0.62, 95 % CI 0.24-1.58, p = 0.295), no relevant effect of blood transfusion on disease-free survival was observed. \r\n\r\n Conclusions: To our knowledge, this is the first propensity score-based analysis providing compelling evidence that the worse oncological outcome after curative resection for advanced cholangiocarcinoma in patients receiving perioperative blood transfusions is caused by the clinical circumstances requiring the transfusions, not by the blood transfusions themselves.","Source":"STN","category":"HUMAN","training_data":"Allogeneic Blood Transfusion Does Not Affect Outcome After Curative Resection For Advanced Cholangiocarcinoma Purpose: To assess the impact of perioperative blood transfusion on overall and disease-free survival in patients undergoing curative resection for cholangiocarcinoma. \r\n\r\n Methods: In a single-center study, 128 patients undergoing curative resection for cholangiocarcinoma between 2001 and 2010 were assessed. The median follow-up period was 19 months. Transfused and nontransfused patients were compared by Cox regression and propensity score analyses. \r\n\r\n Results: Overall, 38 patients (29.7 %) received blood transfusions. The patient characteristics were highly biased with respect to receiving transfusions (propensity score 0.69 ± 0.22 vs. 0.11 ± 0.16, p < 0.001). In the unadjusted analysis, blood transfusion was associated with a 105 % increased risk of mortality [hazard ratio (HR) 2.05, 95 % CI 1.19-3.51, p = 0.010]. In the multivariate (HR 1.14, 95 % CI 0.52-2.48, p = 0.745) and the propensity score-adjusted Cox regression (HR 1.02, 95 % CI 0.39-2.62, p = 0.974), blood transfusion had no influence on overall survival. Similarly, in the propensity score-adjusted Cox regression (HR 0.62, 95 % CI 0.24-1.58, p = 0.295), no relevant effect of blood transfusion on disease-free survival was observed. \r\n\r\n Conclusions: To our knowledge, this is the first propensity score-based analysis providing compelling evidence that the worse oncological outcome after curative resection for advanced cholangiocarcinoma in patients receiving perioperative blood transfusions is caused by the clinical circumstances requiring the transfusions, not by the blood transfusions themselves. STN","prediction_labels":"HUMAN"},{"cleaned":"safe laparoscopic oncologic re resection incidentally discovered gallbladder cancer propensity score matching analysis non editable google scholar","probabilities":0.9799733,"Title":"Safe Laparoscopic Oncologic Re-Resection Of Incidentally Discovered Gallbladder Cancer: A Propensity Score Matching Analysis","Abstract":"Non-editable","Source":"Google Scholar","category":"HUMAN","training_data":"Safe Laparoscopic Oncologic Re-Resection Of Incidentally Discovered Gallbladder Cancer: A Propensity Score Matching Analysis Non-editable Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"photodynamic therapy bile duct invasion hepatocellular carcinoma prognosis patients obstructive jaundice caused hepatocellular carcinoma hcc dismal effective biliary drainage difficult due frequent malfunction drainage tube caused hemobilia tumor emboli photodynamic therapy pdt improves biliary patency prolongs survival hilar cholangiocarcinoma aim study assess safety efficacy pdt unresectable hcc bile duct invasion january 2009 september 2010 eleven patients bile duct invasion unresectable hcc enrolled samsung medical center pdt performed 180 j cm 1 light activation 48 hours administration photosensitizer dose 2 mg kg 1 body weight biliary drainages performed patients safety efficacy pdt prospectively evaluated eleven patients successful pdt biliary drainage jaundice improved seven ten patients jaundice pdt hemobilia developed six cases controlled pdt complications photosensitizer 30 day mortality mean survival 140 5 days pdt controlled hemobilia associated bile duct invasion hcc effective treatment option patients google scholar","probabilities":0.9799733,"Title":"Photodynamic Therapy For Bile Duct Invasion Of Hepatocellular Carcinoma","Abstract":"The prognosis of patients with obstructive jaundice caused by hepatocellular carcinoma (HCC) is dismal, because effective biliary drainage is difficult due to frequent malfunction of the drainage tube caused by hemobilia and/or tumor emboli. Photodynamic therapy (PDT) improves biliary patency and prolongs survival in hilar cholangiocarcinoma. The aim of this study was to assess the safety and efficacy of PDT in unresectable HCC with bile duct invasion. Between January 2009 and September 2010, eleven patients with bile duct invasion of unresectable HCC were enrolled at Samsung Medical Center. PDT was performed with 180 J cm−1 light activation 48 hours after administration of the photosensitizer at a dose of 2 mg kg−1 body weight. Biliary drainages were performed in all patients. The safety and efficacy of PDT were prospectively evaluated. Eleven patients had successful PDT and biliary drainage. Jaundice improved in seven out of ten patients who had jaundice before PDT. Hemobilia, which had developed in six cases, was controlled by PDT. There were no complications from the photosensitizer. There was no 30-day mortality, and the mean survival was 140.5 days. PDT controlled hemobilia associated with bile duct invasion of HCC and could be an effective treatment option in these patients.","Source":"Google Scholar","category":"HUMAN","training_data":"Photodynamic Therapy For Bile Duct Invasion Of Hepatocellular Carcinoma The prognosis of patients with obstructive jaundice caused by hepatocellular carcinoma (HCC) is dismal, because effective biliary drainage is difficult due to frequent malfunction of the drainage tube caused by hemobilia and/or tumor emboli. Photodynamic therapy (PDT) improves biliary patency and prolongs survival in hilar cholangiocarcinoma. The aim of this study was to assess the safety and efficacy of PDT in unresectable HCC with bile duct invasion. Between January 2009 and September 2010, eleven patients with bile duct invasion of unresectable HCC were enrolled at Samsung Medical Center. PDT was performed with 180 J cm−1 light activation 48 hours after administration of the photosensitizer at a dose of 2 mg kg−1 body weight. Biliary drainages were performed in all patients. The safety and efficacy of PDT were prospectively evaluated. Eleven patients had successful PDT and biliary drainage. Jaundice improved in seven out of ten patients who had jaundice before PDT. Hemobilia, which had developed in six cases, was controlled by PDT. There were no complications from the photosensitizer. There was no 30-day mortality, and the mean survival was 140.5 days. PDT controlled hemobilia associated with bile duct invasion of HCC and could be an effective treatment option in these patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"paracrine interaction cholangiocellular tumor cells cancer associated fibroblasts activates jak stat signaling pathway increases phosphorilation erk ccc cell lines hucct1 tfk1 abstract available google scholar","probabilities":0.9467213,"Title":"The Paracrine Interaction Of Cholangiocellular Tumor Cells And Cancer-Associated Fibroblasts Activates The Jak/Stat Signaling Pathway And Increases Phosphorilation Of Erk In Ccc Cell Lines Hucct1 And Tfk1","Abstract":"Abstract not available","Source":"Google Scholar","category":"ANIMAL","training_data":"The Paracrine Interaction Of Cholangiocellular Tumor Cells And Cancer-Associated Fibroblasts Activates The Jak/Stat Signaling Pathway And Increases Phosphorilation Of Erk In Ccc Cell Lines Hucct1 And Tfk1 Abstract not available Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"differential expression prognostic value hmga1 pancreatic head periampullary cancer high mortality rate minimal progress made treatment pancreatic cancer last decades warrant alternative approach treatment protocols individualised patient guided prognostic markers particularly interesting target architectural transcription factor high mobility group a1 hmga1 low undetectable normal tissue induced neoplastic transformation consequently often exceptionally high cancer aim current study therefore determine differential expression hmga1 pancreatic head periampullary cancer investigate relation outcome hmga1 expression determined immunohistochemistry original paraffin embedded tissue 99 pancreatic head 112 periampullary cancers r0 expression investigated associations recurrence free rfs cancer specific css overall survival os conventional prognostic factors hmga1 expressed 47 26 pancreatic head periampullary cancer respectively associated poor rfs css os periampullary cancer css 5years following surgery 25 44 patients tumours positive negative hmga1 protein respectively hmga1 expression associated survival pancreatic head cancer conclusion hmga1 identified independent prognostic marker predicting poor outcome periampullary cancer although expressed higher extent compared periampullary cancer hmga1 associated survival pancreatic head cancer pubmed","probabilities":0.7966102,"Title":"Differential expression and prognostic value of HMGA1 in pancreatic head and periampullary cancer","Abstract":"The high mortality rate and minimal progress made in the treatment of pancreatic cancer over the last few decades, warrant an alternative approach. Treatment protocols should be individualised to the patient guided by prognostic markers. A particularly interesting target would be the architectural transcription factor high mobility group A1 (HMGA1), that is low or undetectable in normal tissue, induced during neoplastic transformation and consequently often exceptionally high in cancer. The aim of the current study was therefore to determine the differential expression of HMGA1 in pancreatic head and periampullary cancer and investigate its relation with outcome. HMGA1 expression was determined by immunohistochemistry on original paraffin embedded tissue from 99 pancreatic head- and 112 periampullary cancers (with R0). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS) and conventional prognostic factors. HMGA1 was expressed in 47% and 26% of pancreatic head- and periampullary cancer, respectively and associated with poor RFS, CSS and OS in periampullary cancer. CSS 5years following surgery was 25% and 44% for patients with tumours which were positive or negative for HMGA1 protein, respectively. HMGA1 expression was not associated with survival in pancreatic head cancer. In conclusion HMGA1 was identified as an independent prognostic marker predicting poor outcome in periampullary cancer. Although expressed to a higher extent as compared to periampullary cancer, HMGA1 was not associated with survival in pancreatic head cancer.","Source":"PubMed","category":"HUMAN","training_data":"Differential expression and prognostic value of HMGA1 in pancreatic head and periampullary cancer The high mortality rate and minimal progress made in the treatment of pancreatic cancer over the last few decades, warrant an alternative approach. Treatment protocols should be individualised to the patient guided by prognostic markers. A particularly interesting target would be the architectural transcription factor high mobility group A1 (HMGA1), that is low or undetectable in normal tissue, induced during neoplastic transformation and consequently often exceptionally high in cancer. The aim of the current study was therefore to determine the differential expression of HMGA1 in pancreatic head and periampullary cancer and investigate its relation with outcome. HMGA1 expression was determined by immunohistochemistry on original paraffin embedded tissue from 99 pancreatic head- and 112 periampullary cancers (with R0). Expression was investigated for associations with recurrence free (RFS), cancer specific (CSS) and overall survival (OS) and conventional prognostic factors. HMGA1 was expressed in 47% and 26% of pancreatic head- and periampullary cancer, respectively and associated with poor RFS, CSS and OS in periampullary cancer. CSS 5years following surgery was 25% and 44% for patients with tumours which were positive or negative for HMGA1 protein, respectively. HMGA1 expression was not associated with survival in pancreatic head cancer. In conclusion HMGA1 was identified as an independent prognostic marker predicting poor outcome in periampullary cancer. Although expressed to a higher extent as compared to periampullary cancer, HMGA1 was not associated with survival in pancreatic head cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"lncrna asap1 it1 positively modulates development cholangiocarcinoma via hedgehog signaling pathway past decades lncrnas attracted attentions researchers verified lncrnas modulate multiple biological behaviors various human cancers lncrna asap1 it1 certified tumor facilitator several malignant tumors study aims investigate effects dysregulated asap1 it1 biological processes cholangiocarcinoma high expression level asap1 it1 tested cholangiocarcinoma tissues cells qrt pcr upregulation asap1 predicted unfavorable prognosis cholangiocarcinoma patients next asap1 it1 knocked cancerous cells loss function assay mtt colony formation transwell western bot assays performed demonstrate specific impacts asap1 it1 proliferation migration emt progression cholangiocarcinoma cells results cholangiocarcinoma progression inhibited hedgehog signaling pathway discovered treatment target cholangiocarcinoma study interaction asap1 it1 hedgehog pathway specifically investigated smo gli1 two hedgehog related proteins examined cholangiocarcinoma cells results qrt pcr western blot assay suggested asap1 it1 positively modulate smo gli1 cholangiocarcinoma finally rescue assays carried prove asap1 it1 improve cholangiocarcinoma progression development via hedgehog signaling pathway stn","probabilities":1.0,"Title":"Lncrna Asap1-It1 Positively Modulates The Development Of Cholangiocarcinoma Via Hedgehog Signaling Pathway","Abstract":"Over the past decades, lncRNAs have attracted more and more attentions of researchers. It has been verified that lncRNAs can modulate multiple biological behaviors in various human cancers. LncRNA ASAP1-IT1 has been certified to be a tumor facilitator in several malignant tumors. This study aims to investigate the effects of dysregulated ASAP1-IT1 on biological processes of Cholangiocarcinoma. The high expression level of ASAP1-IT1 was tested in Cholangiocarcinoma tissues and cells with qRT-PCR. Upregulation of ASAP1-IT predicted the unfavorable prognosis for Cholangiocarcinoma patients. Next, ASAP1-IT1 was knocked down in cancerous cells for loss-of function assay. MTT, colony formation and transwell and western bot assays were performed to demonstrate the specific impacts of ASAP1-IT1 on proliferation, migration and EMT progression of Cholangiocarcinoma. Cells. As a results, the Cholangiocarcinoma progression was inhibited. Hedgehog signaling pathway has been discovered to be a treatment target in Cholangiocarcinoma. In this study, the interaction between ASAP1-IT1 and hedgehog pathway was specifically investigated. Smo and Gli1, two hedgehog-related proteins were examined in Cholangiocarcinoma cells. The results of qRT-PCR and western blot assay suggested that ASAP1-IT1 could positively modulate Smo and Gli1 in Cholangiocarcinoma. Finally, rescue assays were carried out to prove that ASAP1-IT1 could improve Cholangiocarcinoma progression and development via hedgehog signaling pathway.","Source":"STN","category":"ANIMAL","training_data":"Lncrna Asap1-It1 Positively Modulates The Development Of Cholangiocarcinoma Via Hedgehog Signaling Pathway Over the past decades, lncRNAs have attracted more and more attentions of researchers. It has been verified that lncRNAs can modulate multiple biological behaviors in various human cancers. LncRNA ASAP1-IT1 has been certified to be a tumor facilitator in several malignant tumors. This study aims to investigate the effects of dysregulated ASAP1-IT1 on biological processes of Cholangiocarcinoma. The high expression level of ASAP1-IT1 was tested in Cholangiocarcinoma tissues and cells with qRT-PCR. Upregulation of ASAP1-IT predicted the unfavorable prognosis for Cholangiocarcinoma patients. Next, ASAP1-IT1 was knocked down in cancerous cells for loss-of function assay. MTT, colony formation and transwell and western bot assays were performed to demonstrate the specific impacts of ASAP1-IT1 on proliferation, migration and EMT progression of Cholangiocarcinoma. Cells. As a results, the Cholangiocarcinoma progression was inhibited. Hedgehog signaling pathway has been discovered to be a treatment target in Cholangiocarcinoma. In this study, the interaction between ASAP1-IT1 and hedgehog pathway was specifically investigated. Smo and Gli1, two hedgehog-related proteins were examined in Cholangiocarcinoma cells. The results of qRT-PCR and western blot assay suggested that ASAP1-IT1 could positively modulate Smo and Gli1 in Cholangiocarcinoma. Finally, rescue assays were carried out to prove that ASAP1-IT1 could improve Cholangiocarcinoma progression and development via hedgehog signaling pathway. STN","prediction_labels":"ANIMAL"},{"cleaned":"clinicopathologic features advanced gallbladder cancer associated adenomyomatosis adenomyomatosis gallbladder considered malignant potential gross features adenomyomatosis sometimes encountered gallbladders resected diagnosis gallbladder carcinoma purpose study determine clinicopathologic features survival rates cases gallbladder cancer gross features adenomyomatosis study subjects 97 surgically treated gallbladder carcinoma patients gallbladder showing typical gross features adenomyomatosis judged adenomyomatosis positive gallbladder cancer terms gross findings 25 cases 25 8 classified adenomyomatosis positive status adenomyomatosis significantly associated stage p 0 0004 lymph node ln metastasis p 0 0001 distant metastasis p 0 008 stage p 0 0005 adenomyomatosis positive group 16 25 cases 64 0 classified segmental type 9 cases 36 0 classified fundal type diffuse type cases present series status adenomyomatosis correlated significantly survival p 0 0007 however multivariate analysis significant variables identified univariate analysis identified stage p 0 0178 ln metastasis p 0 0048 independent prognostic factors subset analysis stage according status adenomyomatosis showed significant impact survival results indicate adenomyomatosis positive gallbladder cancer often diagnosed clinically advanced stages since preceding adenomyomatosis may prevent early detection gallbladder cancer usefulness preventive cholecystectomy cases asymptomatic adenomyomatosis considered pubmed","probabilities":0.9799733,"Title":"Clinicopathologic features of advanced gallbladder cancer associated with adenomyomatosis","Abstract":"Adenomyomatosis of the gallbladder has not been considered to have malignant potential, but gross features of adenomyomatosis are sometimes encountered in gallbladders resected under a diagnosis of gallbladder carcinoma. The purpose of this study was to determine the clinicopathologic features and survival rates in cases of gallbladder cancer with gross features of adenomyomatosis. The study subjects were 97 surgically treated gallbladder carcinoma patients. Only gallbladder showing typical gross features of adenomyomatosis was judged as adenomyomatosis-positive gallbladder cancer. In terms of gross findings, 25 cases (25.8%) were classified as adenomyomatosis-positive. The status of adenomyomatosis was significantly associated with the T stage (P=0.0004), lymph node (LN) metastasis (P<0.0001), distant metastasis (P=0.008), and stage (P=0.0005). In the adenomyomatosis-positive group, 16 of the 25 cases (64.0%) were classified as segmental type and 9 cases (36.0%) were classified as fundal type. No diffuse-type cases were present in this series. The status of adenomyomatosis correlated significantly with survival (P=0.0007). However, the multivariate analysis of significant variables identified from the univariate analysis identified only T stage (P=0.0178) and LN metastasis (P=0.0048) as independent prognostic factors. Subset analysis with T stage according to the status of adenomyomatosis showed no significant impact on survival. These results indicate that adenomyomatosis-positive gallbladder cancer is more often diagnosed clinically in the advanced stages. Since preceding adenomyomatosis may prevent the early detection of gallbladder cancer, the usefulness of preventive cholecystectomy in cases of asymptomatic adenomyomatosis should be considered.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathologic features of advanced gallbladder cancer associated with adenomyomatosis Adenomyomatosis of the gallbladder has not been considered to have malignant potential, but gross features of adenomyomatosis are sometimes encountered in gallbladders resected under a diagnosis of gallbladder carcinoma. The purpose of this study was to determine the clinicopathologic features and survival rates in cases of gallbladder cancer with gross features of adenomyomatosis. The study subjects were 97 surgically treated gallbladder carcinoma patients. Only gallbladder showing typical gross features of adenomyomatosis was judged as adenomyomatosis-positive gallbladder cancer. In terms of gross findings, 25 cases (25.8%) were classified as adenomyomatosis-positive. The status of adenomyomatosis was significantly associated with the T stage (P=0.0004), lymph node (LN) metastasis (P<0.0001), distant metastasis (P=0.008), and stage (P=0.0005). In the adenomyomatosis-positive group, 16 of the 25 cases (64.0%) were classified as segmental type and 9 cases (36.0%) were classified as fundal type. No diffuse-type cases were present in this series. The status of adenomyomatosis correlated significantly with survival (P=0.0007). However, the multivariate analysis of significant variables identified from the univariate analysis identified only T stage (P=0.0178) and LN metastasis (P=0.0048) as independent prognostic factors. Subset analysis with T stage according to the status of adenomyomatosis showed no significant impact on survival. These results indicate that adenomyomatosis-positive gallbladder cancer is more often diagnosed clinically in the advanced stages. Since preceding adenomyomatosis may prevent the early detection of gallbladder cancer, the usefulness of preventive cholecystectomy in cases of asymptomatic adenomyomatosis should be considered. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical treatment advanced gallbladder cancer objective radical lymph node dissection surgery advanced gallbladder cancer controversial purpose study evaluate different extent lymph node dissection n2 stage gallbladder cancer patients patients methods retrospective analysis made 60 patients n2 stage underwent standard regional lymphadenectomy srln extended regional lymphadenectomy erln september 2000 june 2011 60 advanced gallbladder cancer patients n2 stage lymph node metastasis included study curative effects different extent lymphadenctomy lymph node n2 stage gallbladder cancer patients compared results median survival time 34 83 months srln group 30 28 months erln group significant difference survival rate srln erln group p 0 51 postoperative major morbidity mortality rates 64 3 7 14 srln group 81 3 9 34 erln group respectively moreover number positive lymph nodes chemotherapy found correlate survival univariate analyses p 0 05 conclusions advanced gallbladder patients n2 stage lymph node metastasis erln provide significant survival benefit srln rate morbidity mortality erln exceptionally high erln therefore considered advanced gallbladder cancers n2 stage pubmed","probabilities":0.9799733,"Title":"Surgical treatment of advanced gallbladder cancer","Abstract":"OBJECTIVE: Radical lymph node dissection in surgery for advanced gallbladder cancer is controversial. The purpose of this study is to evaluate the different extent of lymph node dissection for N2 stage gallbladder cancer patients. PATIENTS AND METHODS: A retrospective analysis was made of 60 patients with N2 stage who underwent standard regional lymphadenectomy (SRLN) and extended regional lymphadenectomy (ERLN). Between September 2000 and June 2011, 60 advanced gallbladder cancer patients with N2 stage of lymph node metastasis were included in this study. The curative effects with different extent of lymphadenctomy for lymph node N2 stage of gallbladder cancer patients were compared. RESULTS: The median survival time was 34.83 months in the SRLN group and 30.28 months in the ERLN group. There was no significant difference of survival rate between SRLN and ERLN group (P=0.51). Postoperative major morbidity and mortality rates were 64.3% and 7.14% in the SRLN group, 81.3% and 9.34% in the ERLN group, respectively. Moreover, the number of positive lymph nodes and chemotherapy were found to correlate with survival on univariate analyses (P<0.05). CONCLUSIONS: For advanced gallbladder patients with N2 stage lymph node metastasis, ERLN cannot provide a significant survival benefit over SRLN and the rate of morbidity and mortality in ERLN is exceptionally high. ERLN therefore should not be considered in the advanced gallbladder cancers with N2 stage.","Source":"PubMed","category":"HUMAN","training_data":"Surgical treatment of advanced gallbladder cancer OBJECTIVE: Radical lymph node dissection in surgery for advanced gallbladder cancer is controversial. The purpose of this study is to evaluate the different extent of lymph node dissection for N2 stage gallbladder cancer patients. PATIENTS AND METHODS: A retrospective analysis was made of 60 patients with N2 stage who underwent standard regional lymphadenectomy (SRLN) and extended regional lymphadenectomy (ERLN). Between September 2000 and June 2011, 60 advanced gallbladder cancer patients with N2 stage of lymph node metastasis were included in this study. The curative effects with different extent of lymphadenctomy for lymph node N2 stage of gallbladder cancer patients were compared. RESULTS: The median survival time was 34.83 months in the SRLN group and 30.28 months in the ERLN group. There was no significant difference of survival rate between SRLN and ERLN group (P=0.51). Postoperative major morbidity and mortality rates were 64.3% and 7.14% in the SRLN group, 81.3% and 9.34% in the ERLN group, respectively. Moreover, the number of positive lymph nodes and chemotherapy were found to correlate with survival on univariate analyses (P<0.05). CONCLUSIONS: For advanced gallbladder patients with N2 stage lymph node metastasis, ERLN cannot provide a significant survival benefit over SRLN and the rate of morbidity and mortality in ERLN is exceptionally high. ERLN therefore should not be considered in the advanced gallbladder cancers with N2 stage. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role adjuvant radiotherapy localized extrahepatic bile duct cancer objective evaluate benefit adjuvant radiotherapy rt surgical resection extrahepatic bile duct ehbd cancer methods 1997 2015 59 patients ehbd cancer subject study 36 patients undergoing adjuvant treatment surgery observation group 23 patients receiving adjuvant rt rt group compared microscopic residual disease r1 9 25 patients 5 22 patients macroscopic residual disease r2 2 6 patients 6 26 patients observation rt groups respectively adjuvant rt delivered tumour bed regional lymph nodes 50 4 gy range 45 61 gy results median follow 19 months local recurrence observed 10 28 patients 2 9 patients observation rt groups respectively univariate analysis 5 year local recurrence free survival lrfs rates 50 observation group 54 rt group p 0 401 5 year overall survival os rates 29 3 observation group 26 3 rt group p 0 602 multivariable analysis however adjuvant rt significantly improved lrfs hazard ratio hr 0 310 95 confidence interval ci 0 100 0 963 p 0 043 trend towards increased os hr 0 491 95 ci 0 219 1 102 p 0 085 resection margin rm status also correlated lrfs hr r1 6 134 95 ci 2 051 18 344 hr r2 18 551 95 ci 3 680 93 520 p 0 001 os hr r1 1 816 95 ci 0 853 3 867 hr r2 3 564 95 ci 1 175 10 809 p 0 054 conclusion rm status significant prognosticator ehbd cancer adjuvant rt improved local control rate thereby survival rate might increased advances knowledge benefit adjuvant rt ehbd cancer demonstrated via comparison observation group pubmed","probabilities":0.9799733,"Title":"Role of adjuvant radiotherapy for localized extrahepatic bile duct cancer","Abstract":"OBJECTIVE: To evaluate the benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic bile duct (EHBD) cancer. METHODS: From 1997 to 2015, 59 patients with EHBD cancer were the subject of this study; 36 patients not undergoing adjuvant treatment after surgery (observation group) and 23 patients receiving adjuvant RT (RT group) were compared. Microscopic residual disease (R1) was in 9 (25%) patients and 5 (22%) patients, and macroscopic residual disease (R2) was in 2 (6%) patients and 6 (26%) patients in the observation and RT groups, respectively. Adjuvant RT was delivered to the tumour bed and regional lymph nodes up to 50.4 Gy (range, 45-61 Gy). RESULTS: With a median follow-up of 19 months, local recurrence was observed in 10 (28%) patients and 2 (9%) patients in the observation and RT groups, respectively. On univariate analysis, the 5-year local recurrence-free survival (LRFS) rates were 50% in the observation group and 54% in the RT group (p = 0.401). The 5-year overall survival (OS) rates were 29.3% in the observation group and 26.3% in the RT group (p = 0.602). On multivariable analysis, however, adjuvant RT significantly improved LRFS [hazard ratio (HR), 0.310; 95% confidence interval (CI), 0.100-0.963; p = 0.043] and had a trend towards increased OS (HR, 0.491; 95% CI, 0.219-1.102; p = 0.085). Resection margin (RM) status was also correlated with LRFS (HR for R1 6.134, 95% CI 2.051-18.344; and HR for R2 18.551, 95% CI 3.680-93.520; p < 0.001) and OS (HR for R1 1.816, 95% CI 0.853-3.867; and HR for R2 3.564, 95% CI 1.175-10.809; p = 0.054). CONCLUSION: RM status was a significant prognosticator of EHBD cancer, and adjuvant RT improved local control rate; thereby, survival rate might be increased. Advances in knowledge: The benefit of adjuvant RT in EHBD cancer was demonstrated via comparison with observation group.","Source":"PubMed","category":"HUMAN","training_data":"Role of adjuvant radiotherapy for localized extrahepatic bile duct cancer OBJECTIVE: To evaluate the benefit of adjuvant radiotherapy (RT) after surgical resection for extrahepatic bile duct (EHBD) cancer. METHODS: From 1997 to 2015, 59 patients with EHBD cancer were the subject of this study; 36 patients not undergoing adjuvant treatment after surgery (observation group) and 23 patients receiving adjuvant RT (RT group) were compared. Microscopic residual disease (R1) was in 9 (25%) patients and 5 (22%) patients, and macroscopic residual disease (R2) was in 2 (6%) patients and 6 (26%) patients in the observation and RT groups, respectively. Adjuvant RT was delivered to the tumour bed and regional lymph nodes up to 50.4 Gy (range, 45-61 Gy). RESULTS: With a median follow-up of 19 months, local recurrence was observed in 10 (28%) patients and 2 (9%) patients in the observation and RT groups, respectively. On univariate analysis, the 5-year local recurrence-free survival (LRFS) rates were 50% in the observation group and 54% in the RT group (p = 0.401). The 5-year overall survival (OS) rates were 29.3% in the observation group and 26.3% in the RT group (p = 0.602). On multivariable analysis, however, adjuvant RT significantly improved LRFS [hazard ratio (HR), 0.310; 95% confidence interval (CI), 0.100-0.963; p = 0.043] and had a trend towards increased OS (HR, 0.491; 95% CI, 0.219-1.102; p = 0.085). Resection margin (RM) status was also correlated with LRFS (HR for R1 6.134, 95% CI 2.051-18.344; and HR for R2 18.551, 95% CI 3.680-93.520; p < 0.001) and OS (HR for R1 1.816, 95% CI 0.853-3.867; and HR for R2 3.564, 95% CI 1.175-10.809; p = 0.054). CONCLUSION: RM status was a significant prognosticator of EHBD cancer, and adjuvant RT improved local control rate; thereby, survival rate might be increased. Advances in knowledge: The benefit of adjuvant RT in EHBD cancer was demonstrated via comparison with observation group. PubMed","prediction_labels":"HUMAN"},{"cleaned":"sox9 expression decreases survival patients intrahepatic cholangiocarcinoma conferring chemoresistance background sex determining region y box sry box containing gene 9 sox9 expression confers cancer stem cell features however sox9 function intrahepatic cholangiocarcinoma icca unknown study investigated effects underlying mechanisms sox9 icca methods sox9 expression 59 icca patients examined immunohistochemistry association sox9 expression clinical outcome evaluated gene signature biological functions sox9 icca examined vitro results icca patients high sox9 expression shorter survival time low sox9 patients receiving chemotherapy median survival time patients low high levels sox9 62 22 months respectively vitro gemcitabine increased sox9 expression icca cells sox9 knocked gemcitabine induced apoptosis markedly increased silencing sox9 significantly inhibited gemcitabine induced phosphorylation checkpoint kinase 1 key cell cycle checkpoint protein coordinates dna damage response inhibited expression multidrug resistance genes microarray analyses showed sox9 knockdown cca cells altered gene signatures associated multidrug resistance p53 signalling conclusions sox9 governs response cca cells chemotherapy sox9 biomarker select icca patients eligible efficient chemotherapy stn","probabilities":0.9467213,"Title":"Sox9 Expression Decreases Survival Of Patients With Intrahepatic Cholangiocarcinoma By Conferring Chemoresistance","Abstract":"Background: Sex-determining region Y-box (SRY-box) containing gene 9 (SOX9) expression confers cancer stem cell features. However, SOX9 function in intrahepatic cholangiocarcinoma (iCCA) is unknown. This study investigated the effects and underlying mechanisms of SOX9 in iCCA. \n\n Methods: SOX9 expression in 59 iCCA patients was examined by immunohistochemistry. The association between SOX9 expression and clinical outcome was evaluated. Gene signature and biological functions of SOX9 in iCCA were examined in vitro. \n\n Results: iCCA patients with high SOX9 expression had shorter survival time than those with low SOX9. In patients receiving chemotherapy, median survival time in patients with low and high levels of SOX9 were 62 and 22 months, respectively. In vitro, gemcitabine increased SOX9 expression in iCCA cells. When SOX9 was knocked down, gemcitabine-induced apoptosis was markedly increased. Silencing SOX9 significantly inhibited gemcitabine-induced phosphorylation of checkpoint kinase 1, a key cell cycle checkpoint protein that coordinates the DNA damage response and inhibited the expression of multidrug resistance genes. Microarray analyses showed that SOX9 knockdown in CCA cells altered gene signatures associated with multidrug resistance and p53 signalling. \n\n Conclusions: SOX9 governs the response of CCA cells to chemotherapy. SOX9 is a biomarker to select iCCA patients eligible for efficient chemotherapy.","Source":"STN","category":"ANIMAL","training_data":"Sox9 Expression Decreases Survival Of Patients With Intrahepatic Cholangiocarcinoma By Conferring Chemoresistance Background: Sex-determining region Y-box (SRY-box) containing gene 9 (SOX9) expression confers cancer stem cell features. However, SOX9 function in intrahepatic cholangiocarcinoma (iCCA) is unknown. This study investigated the effects and underlying mechanisms of SOX9 in iCCA. \n\n Methods: SOX9 expression in 59 iCCA patients was examined by immunohistochemistry. The association between SOX9 expression and clinical outcome was evaluated. Gene signature and biological functions of SOX9 in iCCA were examined in vitro. \n\n Results: iCCA patients with high SOX9 expression had shorter survival time than those with low SOX9. In patients receiving chemotherapy, median survival time in patients with low and high levels of SOX9 were 62 and 22 months, respectively. In vitro, gemcitabine increased SOX9 expression in iCCA cells. When SOX9 was knocked down, gemcitabine-induced apoptosis was markedly increased. Silencing SOX9 significantly inhibited gemcitabine-induced phosphorylation of checkpoint kinase 1, a key cell cycle checkpoint protein that coordinates the DNA damage response and inhibited the expression of multidrug resistance genes. Microarray analyses showed that SOX9 knockdown in CCA cells altered gene signatures associated with multidrug resistance and p53 signalling. \n\n Conclusions: SOX9 governs the response of CCA cells to chemotherapy. SOX9 is a biomarker to select iCCA patients eligible for efficient chemotherapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"gemcitabine based adjuvant chemotherapy patients advanced gallbladder cancer aim investigated effects gemcitabine based adjuvant chemotherapy gem prognosis patients gallbladder cancer patients methods retrospectively analyzed outcomes 36 patients underwent radical resection gallbladder cancer 2001 2012 using 2 prognostic factors kaplan meier estimator log rank tests survival data results gem group higher rates lymph node positivity distant metastasis higher uicc stage fewer r0 resections 5 year survival rate 60 significantly differ controls 70 0 gem significant prognostic factor univariate analysis however among patients underwent r1 r2 resections gem significantly improved prognosis univariate multivariate analyses median survival r1 2 gem group 66 4 months significantly better controls 5 4 months p 0 002 conclusion gem improved prognosis patients gallbladder cancer r1 r2 resections pubmed","probabilities":0.9799733,"Title":"Gemcitabine-based adjuvant chemotherapy for patients with advanced gallbladder cancer","Abstract":"AIM: We investigated effects of gemcitabine-based adjuvant chemotherapy (GEM) on prognosis of patients with gallbladder cancer. PATIENTS AND METHODS: We retrospectively analyzed outcomes of 36 patients who underwent radical resection for gallbladder cancer from 2001 through to 2012, using χ(2) for prognostic factors and Kaplan-Meier estimator and log-rank tests for survival data. RESULTS: The GEM group had higher rates of lymph node positivity and distant metastasis, higher UICC stage and fewer R0 resections; their 5-year survival rate (60%) did not significantly differ from that of the controls (70.0%), nor was GEM a significant prognostic factor in univariate analysis. However, among patients who underwent R1 and R2 resections, GEM significantly improved prognosis in both univariate and multivariate analyses. Median survival of the R1/2 GEM group (66.4 months) was significantly better than that of controls (5.4 months) (p=0.002). CONCLUSION: GEM improved prognosis of patients with gallbladder cancer after R1/R2 resections.","Source":"PubMed","category":"HUMAN","training_data":"Gemcitabine-based adjuvant chemotherapy for patients with advanced gallbladder cancer AIM: We investigated effects of gemcitabine-based adjuvant chemotherapy (GEM) on prognosis of patients with gallbladder cancer. PATIENTS AND METHODS: We retrospectively analyzed outcomes of 36 patients who underwent radical resection for gallbladder cancer from 2001 through to 2012, using χ(2) for prognostic factors and Kaplan-Meier estimator and log-rank tests for survival data. RESULTS: The GEM group had higher rates of lymph node positivity and distant metastasis, higher UICC stage and fewer R0 resections; their 5-year survival rate (60%) did not significantly differ from that of the controls (70.0%), nor was GEM a significant prognostic factor in univariate analysis. However, among patients who underwent R1 and R2 resections, GEM significantly improved prognosis in both univariate and multivariate analyses. Median survival of the R1/2 GEM group (66.4 months) was significantly better than that of controls (5.4 months) (p=0.002). CONCLUSION: GEM improved prognosis of patients with gallbladder cancer after R1/R2 resections. PubMed","prediction_labels":"HUMAN"},{"cleaned":"etoposide radiosensitizes p53 defective cholangiocarcinoma cell lines independent g2 checkpoint efficacies radiotherapy accounted comprehensive cancer treatment modality past decades however failure treatment modality occurs several malignancies due resistance cancer cells radiation previously reported present authors defective cell cycle checkpoints used biomarkers predicting responsiveness radiation individual patients cholangiocarcinoma cca however identification functional defective cell cycle checkpoints cells patient tissues cumbersome applicable clinic present study evaluated radiosensitization potential etoposide p53 defective cca kku m055 kku m214 cell lines treatment etoposide enhanced responsiveness two p53 defective cca cell lines radiation independent g2 checkpoint function addition etoposide treatment increased radiation induced cell death without altering dominant mode cell death two cell lines findings indicate etoposide used radiation sensitizer p53 defective tumors independent function g2 checkpoint stn","probabilities":0.9467213,"Title":"Etoposide Radiosensitizes P53-Defective Cholangiocarcinoma Cell Lines Independent Of Their G2 Checkpoint Efficacies","Abstract":"Radiotherapy has been accounted as the most comprehensive cancer treatment modality over the past few decades. However, failure of this treatment modality occurs in several malignancies due to the resistance of cancer cells to radiation. It was previously reported by the present authors that defective cell cycle checkpoints could be used as biomarkers for predicting the responsiveness to radiation in individual patients with cholangiocarcinoma (CCA). However, identification of functional defective cell cycle checkpoints from cells from a patient's tissues is cumbersome and not applicable in the clinic. The present study evaluated the radiosensitization potential of etoposide in p53-defective CCA KKU-M055 and KKU-M214 cell lines. Treatment with etoposide enhanced the responsiveness of two p53-defective CCA cell lines to radiation independent of G2 checkpoint function. In addition, etoposide treatment increased radiation-induced cell death without altering the dominant mode of cell death of the two cell lines. These findings indicate that etoposide could be used as a radiation sensitizer for p53-defective tumors, independent of the function of G2 checkpoint.","Source":"STN","category":"ANIMAL","training_data":"Etoposide Radiosensitizes P53-Defective Cholangiocarcinoma Cell Lines Independent Of Their G2 Checkpoint Efficacies Radiotherapy has been accounted as the most comprehensive cancer treatment modality over the past few decades. However, failure of this treatment modality occurs in several malignancies due to the resistance of cancer cells to radiation. It was previously reported by the present authors that defective cell cycle checkpoints could be used as biomarkers for predicting the responsiveness to radiation in individual patients with cholangiocarcinoma (CCA). However, identification of functional defective cell cycle checkpoints from cells from a patient's tissues is cumbersome and not applicable in the clinic. The present study evaluated the radiosensitization potential of etoposide in p53-defective CCA KKU-M055 and KKU-M214 cell lines. Treatment with etoposide enhanced the responsiveness of two p53-defective CCA cell lines to radiation independent of G2 checkpoint function. In addition, etoposide treatment increased radiation-induced cell death without altering the dominant mode of cell death of the two cell lines. These findings indicate that etoposide could be used as a radiation sensitizer for p53-defective tumors, independent of the function of G2 checkpoint. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic significance contrast enhanced ct attenuation value extrahepatic cholangiocarcinoma objectives determine whether washout characteristics dynamic contrast enhanced computed tomography ct predict survival patients extrahepatic cholangiocarcinoma ehc methods study collected 46 resected cases cases examined dynamic contrast study multidetector row ct region interest measurements obtained non enhanced portal venous phase delayed phase tumour used calculate washout ratio follows attenuation value portal venous phase ct attenuation value delayed enhanced ct attenuation value portal venous phase ct attenuation value unenhanced ct 100 basis median washout ratio classified cases two groups high washout group low washout group associations overall survival various factors including washout rates analysed results median washout ratio 29 4 univariate analysis revealed lower washout ratio venous invasion lymphatic permeation lymph node metastasis associated shorter survival multivariate analysis identified lower washout ratio independent prognostic factor hazard ratio 3 768 p value 0 027 conclusions washout ratio obtained contrast enhanced ct may useful imaging biomarker prediction survival patients ehc key points dynamic contrast study evaluate aggressiveness extrahepatic cholangiocarcinoma lower washout ratio independent prognostic factor overall survival ct predict survival inform decisions surgical options chemotherapy pubmed","probabilities":0.9799733,"Title":"Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma","Abstract":"OBJECTIVES: To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). METHODS: This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT - attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT - attenuation value at unenhanced CT)] × 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. RESULTS: The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). CONCLUSIONS: The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. KEY POINTS: • Dynamic contrast study can evaluate the aggressiveness of extrahepatic cholangiocarcinoma. • A lower washout ratio was an independent prognostic factor for overall survival. • CT can predict survival and inform decisions on surgical options or chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of contrast-enhanced CT attenuation value in extrahepatic cholangiocarcinoma OBJECTIVES: To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). METHODS: This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT - attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT - attenuation value at unenhanced CT)] × 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. RESULTS: The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). CONCLUSIONS: The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. KEY POINTS: • Dynamic contrast study can evaluate the aggressiveness of extrahepatic cholangiocarcinoma. • A lower washout ratio was an independent prognostic factor for overall survival. • CT can predict survival and inform decisions on surgical options or chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"helicobacter pylori biliary tract cancers meta analysis objective helicobacter spp successfully isolated biliary system hypothetical question raised role organisms development biliary tract cancer meta analysis carried explore association helicobacter spp infection biliary tract cancer methods systematic literature search carried identify eligible articles meta analysis used odds ratio random effect model 95 confidence intervals odds ratios calculated heterogeneity quantitatively assessed using test significance set p value 0 01 measured using statistic results ten studies published 2002 2011 finally included meta analysis helicobacter pylori helicobacter bilis helicobacter hepaticus helicobacter ganmani studied heterogeneity 0 p 0 685 significantly higher pooled infection rate helicobacter spp observed biliary tract cancer group compared normal group p 0 0001 benign biliary disease group respectively p 0 0001 studies east asia south asia showed higher prevalence helicobacter spp malignant group evidence supporting higher presence helicobacter spp cancer group obtained using pcr immunohistochemical analysis specimens bile biliary tissues conclusion meta analysis suggests trend higher presence helicobacter spp patients biliary tract cancers compared normal controls benign biliary diseases stn","probabilities":0.88235295,"Title":"Helicobacter Pylori And Biliary Tract Cancers: A Meta-Analysis","Abstract":"Objective: As Helicobacter spp. have been successfully isolated from the biliary system, a hypothetical question was raised about the role of these organisms in the development of biliary tract cancer. This meta-analysis has been carried out to explore the association between Helicobacter spp. infection and biliary tract cancer. \r\n\r\n Methods: A systematic literature search was carried out to identify all eligible articles. Meta-analysis used odds ratio and a random-effect model, and 95% confidence intervals for odds ratios were calculated. Heterogeneity was quantitatively assessed using the χ-test, with significance set at a P-value of 0.01, and was measured using the I-statistic. \r\n\r\n Results: Ten studies published between 2002 and 2011 were finally included for meta-analysis. Helicobacter pylori, Helicobacter bilis, Helicobacter hepaticus, and Helicobacter ganmani were studied. With heterogeneity (I=0%, P=0.685), a significantly higher pooled infection rate of Helicobacter spp. was observed in the biliary tract cancer group compared with the normal group (P=0.0001) and the benign biliary disease group, respectively (P=0.0001). Studies from East Asia and South Asia showed a higher prevalence of Helicobacter spp. in the malignant group. Evidence supporting the higher presence of Helicobacter spp. in the cancer group was obtained using PCR and immunohistochemical analysis of specimens from bile and biliary tissues. \r\n\r\n Conclusion: Our meta-analysis suggests a trend of a higher presence of Helicobacter spp. in patients with biliary tract cancers compared with normal controls or those with benign biliary diseases.","Source":"STN","category":"HUMAN","training_data":"Helicobacter Pylori And Biliary Tract Cancers: A Meta-Analysis Objective: As Helicobacter spp. have been successfully isolated from the biliary system, a hypothetical question was raised about the role of these organisms in the development of biliary tract cancer. This meta-analysis has been carried out to explore the association between Helicobacter spp. infection and biliary tract cancer. \r\n\r\n Methods: A systematic literature search was carried out to identify all eligible articles. Meta-analysis used odds ratio and a random-effect model, and 95% confidence intervals for odds ratios were calculated. Heterogeneity was quantitatively assessed using the χ-test, with significance set at a P-value of 0.01, and was measured using the I-statistic. \r\n\r\n Results: Ten studies published between 2002 and 2011 were finally included for meta-analysis. Helicobacter pylori, Helicobacter bilis, Helicobacter hepaticus, and Helicobacter ganmani were studied. With heterogeneity (I=0%, P=0.685), a significantly higher pooled infection rate of Helicobacter spp. was observed in the biliary tract cancer group compared with the normal group (P=0.0001) and the benign biliary disease group, respectively (P=0.0001). Studies from East Asia and South Asia showed a higher prevalence of Helicobacter spp. in the malignant group. Evidence supporting the higher presence of Helicobacter spp. in the cancer group was obtained using PCR and immunohistochemical analysis of specimens from bile and biliary tissues. \r\n\r\n Conclusion: Our meta-analysis suggests a trend of a higher presence of Helicobacter spp. in patients with biliary tract cancers compared with normal controls or those with benign biliary diseases. STN","prediction_labels":"HUMAN"},{"cleaned":"pilot study novel large bore fully covered self expandable metallic stent unresectable distal biliary malignancies background aim patients unresectable malignant distal biliary obstruction covered self expandable metallic stents csems may remain patent longer uncovered self expandable metallic stents result tumor ingrowth prevention one main cause recurrent biliary obstruction rbo csems sludge formation prevented using large bore stent therefore developed novel 12 mm diameter fully covered sems fcsems investigated clinical safety efficacy rate adverse events methods prospective multicenter pilot study ran june 2011 november 2012 included 38 consecutive patients unresectable malignant distal biliary obstruction patients underwent endoscopic insertion novel stent primary endpoint non rbo rate 6 months placement results technical functional success rates procedures 100 six month non rbo rate 50 median time rbo 184 days median survival time 241 days twelve patients died within 6 months stent placement without rbo rbo observed 10 patients 26 seven experiencing stent occlusion three experiencing stent migration adverse events rbo 30 days developed six patients 16 cholecystitis one pancreatitis one hyperamylasemia one pancreatic ductitis one abdominal pain two stent removal reintervention successfully completed eight patients conclusion novel fcsems may safe effective managing malignant distal obstruction acceptable incidence adverse events pubmed","probabilities":0.9799733,"Title":"Pilot study of a novel, large-bore, fully covered self-expandable metallic stent for unresectable distal biliary malignancies","Abstract":"BACKGROUND AND AIM: In patients with unresectable malignant distal biliary obstruction, covered self-expandable metallic stents (CSEMS) may remain patent longer than uncovered self-expandable metallic stents as a result of tumor ingrowth prevention. One main cause of recurrent biliary obstruction (RBO) in CSEMS is sludge formation, which can be prevented using a large-bore stent. Therefore, we developed a novel, 12-mm diameter fully covered SEMS (FCSEMS) and investigated its clinical safety, efficacy, and rate of adverse events. METHODS: This prospective, multicenter pilot study, which ran between June 2011 and November 2012, included 38 consecutive patients with unresectable malignant distal biliary obstruction. All patients underwent endoscopic insertion of our novel stent. Primary endpoint was non-RBO rate 6 months after placement. RESULTS: Technical and functional success rates of the procedures were 100%. Six-month non-RBO rate was 50%, and median time to RBO was 184 days. Median survival time was 241 days. Twelve patients died within 6 months after stent placement without RBO. RBO was observed in 10 patients (26%), with seven experiencing stent occlusion and three experiencing stent migration. Adverse events other than RBO (at <30 days) developed in six patients (16%; cholecystitis, one; pancreatitis, one; hyperamylasemia, one; pancreatic ductitis, one; abdominal pain, two). Stent removal for reintervention was successfully completed in eight patients. CONCLUSION: Our novel FCSEMS may be safe and effective for managing malignant distal obstruction with an acceptable incidence of adverse events.","Source":"PubMed","category":"HUMAN","training_data":"Pilot study of a novel, large-bore, fully covered self-expandable metallic stent for unresectable distal biliary malignancies BACKGROUND AND AIM: In patients with unresectable malignant distal biliary obstruction, covered self-expandable metallic stents (CSEMS) may remain patent longer than uncovered self-expandable metallic stents as a result of tumor ingrowth prevention. One main cause of recurrent biliary obstruction (RBO) in CSEMS is sludge formation, which can be prevented using a large-bore stent. Therefore, we developed a novel, 12-mm diameter fully covered SEMS (FCSEMS) and investigated its clinical safety, efficacy, and rate of adverse events. METHODS: This prospective, multicenter pilot study, which ran between June 2011 and November 2012, included 38 consecutive patients with unresectable malignant distal biliary obstruction. All patients underwent endoscopic insertion of our novel stent. Primary endpoint was non-RBO rate 6 months after placement. RESULTS: Technical and functional success rates of the procedures were 100%. Six-month non-RBO rate was 50%, and median time to RBO was 184 days. Median survival time was 241 days. Twelve patients died within 6 months after stent placement without RBO. RBO was observed in 10 patients (26%), with seven experiencing stent occlusion and three experiencing stent migration. Adverse events other than RBO (at <30 days) developed in six patients (16%; cholecystitis, one; pancreatitis, one; hyperamylasemia, one; pancreatic ductitis, one; abdominal pain, two). Stent removal for reintervention was successfully completed in eight patients. CONCLUSION: Our novel FCSEMS may be safe and effective for managing malignant distal obstruction with an acceptable incidence of adverse events. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pkm2 regulates neural invasion predicts poor prognosis human hilar cholangiocarcinoma background therapeutic prognostic value glycolytic enzymes hexokinase phosphofructokinase pyruvate kinase pk implicated variety cancers roles treatment prognosis hilar cholangiocarcinoma hc remain unclear study determined expression pkm2 impact biology clinical outcome human hc methods regulation function pkm2 hc pathogenesis evaluated using human tissues molecular cell biology animal models prognostic significance determined according impact patient survival results found expression hexokinase 1 m2 splice isoform pk pkm2 upregulated hc tissues expression correlated tumor recurrence outcome pkm2 expression increased hc cases chronic cholangitis demonstrated isobaric tags relative absolute quantification high pkm2 expression highly correlated high syndecan 2 sdc2 expression neural invasion pkm2 downregulation led decrease sdc2 expression treatment metformin markedly suppressed pkm2 sdc2 expression transcriptional posttranscriptional levels inhibited hc cell proliferation tumor growth conclusions pkm2 regulates neural invasion hc cells least part via regulation sdc2 inhibition pkm2 sdc2 expression contributes therapeutic effect metformin hc therefore pkm2 independent prognostic factor potential therapeutic target human hc stn","probabilities":0.54545456,"Title":"Pkm2 Regulates Neural Invasion Of And Predicts Poor Prognosis For Human Hilar Cholangiocarcinoma","Abstract":"Background: The therapeutic and prognostic value of the glycolytic enzymes hexokinase, phosphofructokinase, and pyruvate kinase (PK) has been implicated in a variety of cancers, while their roles in treatment of and prognosis for hilar cholangiocarcinoma (HC) remain unclear. In this study, we determined the expression of PKM2 in and its impact on biology and clinical outcome of human HC. \r\n\r\n Methods: The regulation and function of PKM2 in HC pathogenesis was evaluated using human tissues, molecular and cell biology, and animal models, and its prognostic significance was determined according to its impact on patient survival. \r\n\r\n Results: We found that expression of hexokinase 1 and the M2 splice isoform of PK (PKM2) was upregulated in HC tissues and that this expression correlated with tumor recurrence and outcome. PKM2 expression was increased in HC cases with chronic cholangitis as demonstrated by isobaric tags for relative and absolute quantification. High PKM2 expression was highly correlated with high syndecan 2 (SDC2) expression and neural invasion. PKM2 downregulation led to a decrease in SDC2 expression. Treatment with metformin markedly suppressed PKM2 and SDC2 expression at both the transcriptional and posttranscriptional levels and inhibited HC cell proliferation and tumor growth. \r\n\r\n Conclusions: PKM2 regulates neural invasion of HC cells at least in part via regulation of SDC2. Inhibition of PKM2 and SDC2 expression contributes to the therapeutic effect of metformin on HC. Therefore, PKM2 is an independent prognostic factor and potential therapeutic target for human HC.","Source":"STN","category":"HUMAN","training_data":"Pkm2 Regulates Neural Invasion Of And Predicts Poor Prognosis For Human Hilar Cholangiocarcinoma Background: The therapeutic and prognostic value of the glycolytic enzymes hexokinase, phosphofructokinase, and pyruvate kinase (PK) has been implicated in a variety of cancers, while their roles in treatment of and prognosis for hilar cholangiocarcinoma (HC) remain unclear. In this study, we determined the expression of PKM2 in and its impact on biology and clinical outcome of human HC. \r\n\r\n Methods: The regulation and function of PKM2 in HC pathogenesis was evaluated using human tissues, molecular and cell biology, and animal models, and its prognostic significance was determined according to its impact on patient survival. \r\n\r\n Results: We found that expression of hexokinase 1 and the M2 splice isoform of PK (PKM2) was upregulated in HC tissues and that this expression correlated with tumor recurrence and outcome. PKM2 expression was increased in HC cases with chronic cholangitis as demonstrated by isobaric tags for relative and absolute quantification. High PKM2 expression was highly correlated with high syndecan 2 (SDC2) expression and neural invasion. PKM2 downregulation led to a decrease in SDC2 expression. Treatment with metformin markedly suppressed PKM2 and SDC2 expression at both the transcriptional and posttranscriptional levels and inhibited HC cell proliferation and tumor growth. \r\n\r\n Conclusions: PKM2 regulates neural invasion of HC cells at least in part via regulation of SDC2. Inhibition of PKM2 and SDC2 expression contributes to the therapeutic effect of metformin on HC. Therefore, PKM2 is an independent prognostic factor and potential therapeutic target for human HC. STN","prediction_labels":"HUMAN"},{"cleaned":"iodine 131 metabolic radiotherapy leads cell death genomic alterations nis overexpression cholangiocarcinoma cholangiocarcinoma cc aggressive liver tumor limited therapeutic options natrium iodide symporter nis mediates uptake iodine thyroid representing key component metabolic radiotherapy using iodine 131 131i treatment thyroid cancer nis expression increased cc providing opportunity novel therapeutic approach type tumor thus study aimed evaluate therapeutic efficacy 131i two human cc cell lines uptake experiments analyzed 131i uptake pro les tumor cell lines study cells irradiated various doses 131i evaluate characterize effects metabolic radiotherapy nis protein expression assessed immunofluorescence methods cell survival evaluated clonogenic assay flow cytometry used assess cell viability type death alterations cell cycle genomic epigenetic characterization cc cells performed irradiation nis gene expression evaluated cc cells rt qpcr results revealed cc cells higher expression nis 131i induced decrease cell survival dose dependent manner increasing irradiation dose decrease cell viability observed consequent increase cell death initial apoptosis karyotype array comparative genomic hybridization acgh analyses revealed cc cell lines near triploid several numerical structural chromosomal rearrangements nis gene expression increased tfk 1 hucct1 cells time dependent manner whole findings study demonstrate presence nis cholangiocarcinoma cell lines crucial decreased cell viability survival observed following exposure cholangiocarcinoma cells 131i stn","probabilities":0.9467213,"Title":"Iodine-131 Metabolic Radiotherapy Leads To Cell Death And Genomic Alterations Through Nis Overexpression On Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CC) is an aggressive liver tumor with limited therapeutic options. Natrium‑iodide symporter (NIS) mediates the uptake of iodine by the thyroid, representing a key component in metabolic radiotherapy using iodine‑131 (131I) for the treatment of thyroid cancer. NIS expression is increased in CC, providing the opportunity for a novel therapeutic approach for this type of tumor. Thus, in this study, we aimed to evaluate therapeutic efficacy of 131I in two human CC cell lines. Uptake experiments analyzed the 131I uptake profiles of the tumor cell lines under study. The cells were irradiated with various doses of 131I to evaluate and characterize the effects of metabolic radiotherapy. NIS protein expression was assessed by immunofluorescence methods. Cell survival was evaluated by clonogenic assay and flow cytometry was used to assess cell viability, and the type of death and alterations in the cell cycle. The genomic and epigenetic characterization of both CC cells was performed before and after irradiation. NIS gene expression was evaluated in the CC cells by RT‑qPCR. The results revealed that CC cells had a higher expression of NIS. 131I induced a decrease in cell survival in a dose‑dependent manner. With the increasing irradiation dose, a decrease in cell viability was observed, with a consequent increase in cell death by initial apoptosis. Karyotype and array comparative genomic hybridization (aCGH) analyses revealed that both CC cell lines were near‑triploid with several numerical and structural chromosomal rearrangements. NIS gene expression was increased in the TFK‑1 and HuCCT1 cells in a time‑dependent manner. On the whole, the findings of this study demonstrate that the presence of NIS in cholangiocarcinoma cell lines is crucial for the decreased cell viability and survival observed following the exposure of cholangiocarcinoma cells to 131I.","Source":"STN","category":"ANIMAL","training_data":"Iodine-131 Metabolic Radiotherapy Leads To Cell Death And Genomic Alterations Through Nis Overexpression On Cholangiocarcinoma Cholangiocarcinoma (CC) is an aggressive liver tumor with limited therapeutic options. Natrium‑iodide symporter (NIS) mediates the uptake of iodine by the thyroid, representing a key component in metabolic radiotherapy using iodine‑131 (131I) for the treatment of thyroid cancer. NIS expression is increased in CC, providing the opportunity for a novel therapeutic approach for this type of tumor. Thus, in this study, we aimed to evaluate therapeutic efficacy of 131I in two human CC cell lines. Uptake experiments analyzed the 131I uptake profiles of the tumor cell lines under study. The cells were irradiated with various doses of 131I to evaluate and characterize the effects of metabolic radiotherapy. NIS protein expression was assessed by immunofluorescence methods. Cell survival was evaluated by clonogenic assay and flow cytometry was used to assess cell viability, and the type of death and alterations in the cell cycle. The genomic and epigenetic characterization of both CC cells was performed before and after irradiation. NIS gene expression was evaluated in the CC cells by RT‑qPCR. The results revealed that CC cells had a higher expression of NIS. 131I induced a decrease in cell survival in a dose‑dependent manner. With the increasing irradiation dose, a decrease in cell viability was observed, with a consequent increase in cell death by initial apoptosis. Karyotype and array comparative genomic hybridization (aCGH) analyses revealed that both CC cell lines were near‑triploid with several numerical and structural chromosomal rearrangements. NIS gene expression was increased in the TFK‑1 and HuCCT1 cells in a time‑dependent manner. On the whole, the findings of this study demonstrate that the presence of NIS in cholangiocarcinoma cell lines is crucial for the decreased cell viability and survival observed following the exposure of cholangiocarcinoma cells to 131I. STN","prediction_labels":"ANIMAL"},{"cleaned":"fruit vegetable fiber intake relation cancer risk findings european prospective investigation cancer nutrition epic fruit vegetables certain components plant foods fiber long thought protect cancer european prospective investigation cancer nutrition epic prospective cohort includes 500 000 participants 10 european countries made substantial contribution knowledge research area purpose article summarize findings published thus far epic study associations fruit vegetable fiber consumption risk cancer 14 different sites risk cancers upper gastrointestinal tract inversely associated fruit intake associated vegetable intake risk colorectal cancer inversely associated intakes total fruit vegetables total fiber risk liver cancer also inversely associated intake total fiber risk cancer lung inversely associated fruit intake associated vegetable intake association fruit intake restricted smokers might influenced residual confounding due smoking borderline inverse association fiber intake breast cancer risk 9 cancer sites studied stomach biliary tract pancreas cervix endometrium prostate kidney bladder lymphoma reported significant associations risk intakes total fruit vegetables fiber pubmed","probabilities":0.9799733,"Title":"Fruit, vegetable, and fiber intake in relation to cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC)","Abstract":"Fruit, vegetables, and certain components of plant foods, such as fiber, have long been thought to protect against cancer. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort that includes >500,000 participants from 10 European countries and has made a substantial contribution to knowledge in this research area. The purpose of this article is to summarize the findings published thus far from the EPIC study on the associations between fruit, vegetable, or fiber consumption and the risk of cancer at 14 different sites. The risk of cancers of the upper gastrointestinal tract was inversely associated with fruit intake but was not associated with vegetable intake. The risk of colorectal cancer was inversely associated with intakes of total fruit and vegetables and total fiber, and the risk of liver cancer was also inversely associated with the intake of total fiber. The risk of cancer of the lung was inversely associated with fruit intake but was not associated with vegetable intake; this association with fruit intake was restricted to smokers and might be influenced by residual confounding due to smoking. There was a borderline inverse association of fiber intake with breast cancer risk. For the other 9 cancer sites studied (stomach, biliary tract, pancreas, cervix, endometrium, prostate, kidney, bladder, and lymphoma) there were no reported significant associations of risk with intakes of total fruit, vegetables, or fiber.","Source":"PubMed","category":"HUMAN","training_data":"Fruit, vegetable, and fiber intake in relation to cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC) Fruit, vegetables, and certain components of plant foods, such as fiber, have long been thought to protect against cancer. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort that includes >500,000 participants from 10 European countries and has made a substantial contribution to knowledge in this research area. The purpose of this article is to summarize the findings published thus far from the EPIC study on the associations between fruit, vegetable, or fiber consumption and the risk of cancer at 14 different sites. The risk of cancers of the upper gastrointestinal tract was inversely associated with fruit intake but was not associated with vegetable intake. The risk of colorectal cancer was inversely associated with intakes of total fruit and vegetables and total fiber, and the risk of liver cancer was also inversely associated with the intake of total fiber. The risk of cancer of the lung was inversely associated with fruit intake but was not associated with vegetable intake; this association with fruit intake was restricted to smokers and might be influenced by residual confounding due to smoking. There was a borderline inverse association of fiber intake with breast cancer risk. For the other 9 cancer sites studied (stomach, biliary tract, pancreas, cervix, endometrium, prostate, kidney, bladder, and lymphoma) there were no reported significant associations of risk with intakes of total fruit, vegetables, or fiber. PubMed","prediction_labels":"HUMAN"},{"cleaned":"body mass index risk gallbladder cancer systematic review meta analysis observational studies objectives provide quantitative assessment association excess body weight interpreted increased body mass index bmi risk gallbladder cancer gbc methods identified eligible studies medline embase 1 february 2015 reference lists retrieved articles summary relative risks 95 confidence intervals calculated random effects model subgroup analyses performed according study design gender geographic location ascertainment exposure adjustment confounders resuits total 12 cohort studies 8 case control studies included meta analysis overall compared normal weight summary relative risks gbc 1 14 95 ci 1 04 1 25 overweight individuals bmi 25 30 kg m 1 56 95 ci 1 41 1 73 obese individuals bmi 30 kg m obese women higher risk gbc men women srrs 1 67 95 ci 1 38 2 02 men srrs 1 42 95 ci 1 21 1 66 significant association overweight gbc risk women srrs 1 26 95 ci 1 13 1 40 men srrs 1 06 95 ci 0 94 1 20 conclusions findings meta analysis indicate obesity associated increased risk gbc especially women overweight associated gbc risk women pubmed","probabilities":0.9799733,"Title":"Body Mass Index and Risk of Gallbladder Cancer: Systematic Review and Meta-Analysis of Observational Studies","Abstract":"OBJECTIVES: To provide a quantitative assessment of the association between excess body weight, interpreted as increased body mass index (BMI), and the risk of gallbladder cancer (GBC). METHODS: We identified eligible studies in Medline and EMBASE up to 1 February 2015, and reference lists of retrieved articles. Summary relative risks with their 95% confidence intervals were calculated in a random-effects model. Subgroup analyses were performed according to study design, gender, geographic location, ascertainment of exposure and adjustment for confounders. RESUITS: A total of 12 cohort studies and 8 case-control studies were included in the meta-analysis. Overall, compared with \"normal\" weight, the summary relative risks of GBC were 1.14 (95% CI, 1.04-1.25) for overweight individuals (BMI 25-30 kg/m²) and 1.56 (95% CI, 1.41-1.73) for obese individuals (BMI > 30 kg/m²). Obese women had a higher risk of GBC than men did (women: SRRs 1.67, 95% CI 1.38-2.02; men: SRRs 1.42, 95% CI 1.21-1.66), and there was significant association between overweight and GBC risk in women (SRRs 1.26, 95% CI 1.13-1.40), but not in men (SRRs 1.06, 95% CI 0.94-1.20). CONCLUSIONS: Findings from this meta-analysis indicate that obesity is associated with an increased risk of GBC, especially in women. Overweight is associated with GBC risk only in women.","Source":"PubMed","category":"HUMAN","training_data":"Body Mass Index and Risk of Gallbladder Cancer: Systematic Review and Meta-Analysis of Observational Studies OBJECTIVES: To provide a quantitative assessment of the association between excess body weight, interpreted as increased body mass index (BMI), and the risk of gallbladder cancer (GBC). METHODS: We identified eligible studies in Medline and EMBASE up to 1 February 2015, and reference lists of retrieved articles. Summary relative risks with their 95% confidence intervals were calculated in a random-effects model. Subgroup analyses were performed according to study design, gender, geographic location, ascertainment of exposure and adjustment for confounders. RESUITS: A total of 12 cohort studies and 8 case-control studies were included in the meta-analysis. Overall, compared with \"normal\" weight, the summary relative risks of GBC were 1.14 (95% CI, 1.04-1.25) for overweight individuals (BMI 25-30 kg/m²) and 1.56 (95% CI, 1.41-1.73) for obese individuals (BMI > 30 kg/m²). Obese women had a higher risk of GBC than men did (women: SRRs 1.67, 95% CI 1.38-2.02; men: SRRs 1.42, 95% CI 1.21-1.66), and there was significant association between overweight and GBC risk in women (SRRs 1.26, 95% CI 1.13-1.40), but not in men (SRRs 1.06, 95% CI 0.94-1.20). CONCLUSIONS: Findings from this meta-analysis indicate that obesity is associated with an increased risk of GBC, especially in women. Overweight is associated with GBC risk only in women. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors operated gallbladder cancer purpose prognosis gallbladder cancer poor lymph node metastasis stage known strongest prognostic factors survival aim study determine importance complementary surgery prognostic factors survival operated gallbladder cancer material method retrospectively analyzed 62 localized gallbladder cancers prognostic factors survival evaluated univariate multivariate analysis results 3 year overall survival os disease free survival dfs rates 52 8 43 5 respectively totally 37 patients 59 6 diagnosed incidentally simple cholecystectomy performed benign causes 56 4 underwent complementary surgery 51 6 recurrence detected 18 4 months follow time r0 resection stage pathological stage found related os dfs univariate analysis grade lymph node metastasis adjuvant chemotherapy also related dfs presence recurrence recurrence side performance score ps perineural invasion pni related os peritoneal metastasis advanced stage disease lymph node metastasis common among patients undergo complementary surgery adjuvant chemotherapy given frequently patients undergone complementary surgery group multivariate analysis indicated grade lymph node metastasis stage recurrence site ps adjuvant chemotherapy stage independent prognostic factors dfs stage prognostic factor os conclusion results showed incidental diagnosis complementary surgery related dfs os stage independent prognostic factor os dfs resected gallbladder cancer pubmed","probabilities":0.9799733,"Title":"Prognostic Factors for Operated Gallbladder Cancer","Abstract":"PURPOSE: The prognosis of gallbladder cancer is poor. Lymph node metastasis and the stage are known to be the strongest prognostic factors for survival. The aim of this study was to determine the importance of complementary surgery and other prognostic factors for survival of operated gallbladder cancer. MATERIAL AND METHOD: We retrospectively analyzed 62 localized gallbladder cancers. The prognostic factors for survival were evaluated by univariate and multivariate analysis. RESULTS: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.8 and 43.5%, respectively. Totally, 37 patients (59.6%) were diagnosed incidentally during simple cholecystectomy which was performed for benign causes but only 56.4% of them underwent complementary surgery. 51.6% of the recurrence was detected during 18.4 months of follow-up time. R0 resection, T stage, and pathological stage were found to be related with both OS and DFS by univariate analysis. Grade, lymph node metastasis, and adjuvant chemotherapy were also related with DFS. Presence of recurrence, recurrence side, performance score (PS), and perineural invasion (PNI) were related with OS. Peritoneal metastasis, advanced stage disease, and lymph node metastasis were more common among patients who did not undergo complementary surgery. Adjuvant chemotherapy was given more frequently to patients who undergone complementary surgery group. The multivariate analysis indicated that grade, lymph node metastasis, stage, recurrence site, PS, and adjuvant chemotherapy stage were independent prognostic factors for DFS on the other and only stage was a prognostic factor for OS. CONCLUSION: Our results showed that incidental diagnosis or complementary surgery was not related with DFS or OS but stage was only an independent prognostic factor for both OS and DFS in resected gallbladder cancer.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Factors for Operated Gallbladder Cancer PURPOSE: The prognosis of gallbladder cancer is poor. Lymph node metastasis and the stage are known to be the strongest prognostic factors for survival. The aim of this study was to determine the importance of complementary surgery and other prognostic factors for survival of operated gallbladder cancer. MATERIAL AND METHOD: We retrospectively analyzed 62 localized gallbladder cancers. The prognostic factors for survival were evaluated by univariate and multivariate analysis. RESULTS: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 52.8 and 43.5%, respectively. Totally, 37 patients (59.6%) were diagnosed incidentally during simple cholecystectomy which was performed for benign causes but only 56.4% of them underwent complementary surgery. 51.6% of the recurrence was detected during 18.4 months of follow-up time. R0 resection, T stage, and pathological stage were found to be related with both OS and DFS by univariate analysis. Grade, lymph node metastasis, and adjuvant chemotherapy were also related with DFS. Presence of recurrence, recurrence side, performance score (PS), and perineural invasion (PNI) were related with OS. Peritoneal metastasis, advanced stage disease, and lymph node metastasis were more common among patients who did not undergo complementary surgery. Adjuvant chemotherapy was given more frequently to patients who undergone complementary surgery group. The multivariate analysis indicated that grade, lymph node metastasis, stage, recurrence site, PS, and adjuvant chemotherapy stage were independent prognostic factors for DFS on the other and only stage was a prognostic factor for OS. CONCLUSION: Our results showed that incidental diagnosis or complementary surgery was not related with DFS or OS but stage was only an independent prognostic factor for both OS and DFS in resected gallbladder cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"micro rna 130a 3p regulates gemcitabine resistance via pparg cholangiocarcinoma background prognosis cholangiocarcinoma cca poor chemoresistance needs reduced study focused micrornas mirnas associated gemcitabine resistance cca assessed clinical significance mirnas target genes methods performed mirna microarray analysis two cca cell lines cclp 1 mzcha 1 gemcitabine resistant gr cells mir 130a 3p mimic induced cca cells using lipofection used pioglitazone peroxisome proliferator activated receptor ppar agonist vitro expression mir 130a 3p studied 27 intrahepatic cca samples laser capture microdissection lcm immunohistochemistry patients undergone curative resection march 2004 november 2012 osaka university hospital results mir 130a 3p expression upregulated cclp 1 grs mzcha 1 grs significantly parental cells transfection mir 130a 3p mimic cca cells increased gemcitabine resistance detected pparg target gene mir 130a 3p furthermore pioglitazone synergistic effect gemcitabine alleviated gemcitabine resistance cca gr cells moreover clinical examination revealed patients underwent adjuvant gemcitabine therapy ppar positive significantly longer disease free survival ppar negative n 5 11 respectively p 0 027 conclusions data suggest mir 130a 3p associated gemcitabine resistance cca pparg possibility pioglitazone used treatment cca pubmed","probabilities":0.875,"Title":"Micro-RNA-130a-3p Regulates Gemcitabine Resistance via PPARG in Cholangiocarcinoma","Abstract":"BACKGROUND: The prognosis of cholangiocarcinoma (CCA) is so poor that its chemoresistance needs to be reduced. In this study, we focused on the microRNAs (miRNAs) associated with gemcitabine resistance of CCA and assessed the clinical significance of miRNAs and their target genes. METHODS: We performed miRNA microarray analysis for two CCA cell lines (CCLP-1 and MzChA-1) and their gemcitabine-resistant (GR) cells. An miR-130a-3p mimic was induced into CCA cells using lipofection, and we used pioglitazone as a peroxisome proliferator-activated receptor-γ (PPARγ) agonist in vitro. The expression of miR-130a-3p was studied in 27 intrahepatic CCA samples after laser capture microdissection (LCM) and by immunohistochemistry from patients who had undergone curative resection from March 2004 to November 2012 at Osaka University Hospital. RESULTS: miR-130a-3p expression was upregulated in CCLP-1-GRs and MzChA-1-GRs significantly more than in their parental cells. Transfection of the miR-130a-3p mimic into CCA cells increased gemcitabine resistance, and we detected PPARG as a target gene of miR-130a-3p. Furthermore, pioglitazone had a synergistic effect with gemcitabine and alleviated gemcitabine resistance of CCA GR cells. Moreover, clinical examination revealed that for patients who underwent adjuvant gemcitabine therapy, those who were PPARγ positive had significantly longer disease-free survival than those who were PPARγ negative (n = 5 and 11, respectively; p = 0.027). CONCLUSIONS: Our data suggest that miR-130a-3p was associated with gemcitabine resistance in CCA through PPARG, and there is a possibility that pioglitazone can be used for the treatment of CCA.","Source":"PubMed","category":"ANIMAL","training_data":"Micro-RNA-130a-3p Regulates Gemcitabine Resistance via PPARG in Cholangiocarcinoma BACKGROUND: The prognosis of cholangiocarcinoma (CCA) is so poor that its chemoresistance needs to be reduced. In this study, we focused on the microRNAs (miRNAs) associated with gemcitabine resistance of CCA and assessed the clinical significance of miRNAs and their target genes. METHODS: We performed miRNA microarray analysis for two CCA cell lines (CCLP-1 and MzChA-1) and their gemcitabine-resistant (GR) cells. An miR-130a-3p mimic was induced into CCA cells using lipofection, and we used pioglitazone as a peroxisome proliferator-activated receptor-γ (PPARγ) agonist in vitro. The expression of miR-130a-3p was studied in 27 intrahepatic CCA samples after laser capture microdissection (LCM) and by immunohistochemistry from patients who had undergone curative resection from March 2004 to November 2012 at Osaka University Hospital. RESULTS: miR-130a-3p expression was upregulated in CCLP-1-GRs and MzChA-1-GRs significantly more than in their parental cells. Transfection of the miR-130a-3p mimic into CCA cells increased gemcitabine resistance, and we detected PPARG as a target gene of miR-130a-3p. Furthermore, pioglitazone had a synergistic effect with gemcitabine and alleviated gemcitabine resistance of CCA GR cells. Moreover, clinical examination revealed that for patients who underwent adjuvant gemcitabine therapy, those who were PPARγ positive had significantly longer disease-free survival than those who were PPARγ negative (n = 5 and 11, respectively; p = 0.027). CONCLUSIONS: Our data suggest that miR-130a-3p was associated with gemcitabine resistance in CCA through PPARG, and there is a possibility that pioglitazone can be used for the treatment of CCA. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"dna methylation epigenetic regulator gallbladder cancer overview gallbladder cancer gbc lethal health issue affecting mostly women middle age high incidence gbc reported across world specifically asian countries india pakistan exact etiology remains unknown although several risk factors genetic aberrations involving mutations epigenetic changes may involved gallbladder carcinogenesis article presents review published literature mainly year 2003 onwards topic main concerns epigenetic regulation gbc relevant studies identified included described according aforementioned subheadings review discussed role dna methylation gbc clinical implication future prospects biomarker development early diagnosis therapeutic interventions pubmed","probabilities":0.9799733,"Title":"DNA methylation as an epigenetic regulator of gallbladder cancer: An overview","Abstract":"Gallbladder cancer (GBC) is a lethal health issue affecting mostly the women in their middle-age. High incidence of GBC has been reported across the world specifically in Asian countries, India and Pakistan. The exact etiology remains unknown, although several risk factors and genetic aberrations involving mutations or epigenetic changes may be involved in gallbladder carcinogenesis. This article presents a review of the published literature mainly from the year 2003 onwards. The topic of main concerns was epigenetic regulation of GBC. All relevant studies identified were included and are described according to the aforementioned subheadings. In this review, we have discussed the role of DNA methylation in GBC, clinical implication and future prospects of biomarker development for early diagnosis and therapeutic interventions.","Source":"PubMed","category":"HUMAN","training_data":"DNA methylation as an epigenetic regulator of gallbladder cancer: An overview Gallbladder cancer (GBC) is a lethal health issue affecting mostly the women in their middle-age. High incidence of GBC has been reported across the world specifically in Asian countries, India and Pakistan. The exact etiology remains unknown, although several risk factors and genetic aberrations involving mutations or epigenetic changes may be involved in gallbladder carcinogenesis. This article presents a review of the published literature mainly from the year 2003 onwards. The topic of main concerns was epigenetic regulation of GBC. All relevant studies identified were included and are described according to the aforementioned subheadings. In this review, we have discussed the role of DNA methylation in GBC, clinical implication and future prospects of biomarker development for early diagnosis and therapeutic interventions. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence mortality primary liver cancer england wales changing patterns ethnic variations aim explore recent trends modes diagnosis ethnic distribution mortality incidence ratio primary liver cancer subtypes england wales methods obtained incidence 1979 2008 mortality 1968 2008 data primary liver cancer england wales calculated age standardised incidence mortality rates trends age standardised mortality asmr incidence asir rates basis diagnosis primary liver cancer subcategories hepatocellular carcinoma intrahepatic bile duct unspecified liver tumours analysed study period changes guidelines diagnosis primary liver cancer plc may impact changing trends rates may obtained thus explored changes mode diagnosis reported cancer registries furthermore examined distribution tumours ethnicity statistical manipulations data carried microsoft excel seattle washington united sttaes additional epidemiological statistics done epi info software atlanta ga united sttaes define patterns change time evaluated trends asmr asir plc intrahepatic bile duct carcinoma ihbd using least squares regression line fitted natural logarithm mortality incidence rates estimated patterns survival subsequent 5 10 years using complement mortality incidence ratio 1 mir results age standardised mortality rate primary liver cancer increased sexes 2 56 1 29 100000 1968 5 10 2 63 100000 2008 men women respectively use histology diagnostic confirmation primary liver cancer increased 35 7 registered cases 1993 plateau 50 2005 2008 reliance cytology basis diagnosis maintained downward trend throughout study period although approximately 30 plc registrations information ethnicity relatively higher registration major tumour subtypes patients whose ethnic backgrounds high incident regions world survival plc estimated get poorer 10 years 2018 relative 2008 particularly result ihbd conclusion incidence mortality plc particularly ihbd continued rise england wales changes modes diagnosis may contributing pubmed","probabilities":0.9799733,"Title":"Incidence and mortality of primary liver cancer in England and Wales: changing patterns and ethnic variations","Abstract":"AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. METHODS: We obtained incidence (1979-2008) and mortality (1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality (ASMR) and incidence (ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer (PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel® (Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software (Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma (IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio (1-MIR). RESULTS: Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had information on ethnicity, there was a relatively higher registration of the major tumour subtypes in patients whose ethnic backgrounds were from high incident regions of the world. Survival from PLC is estimated to get poorer in 10 years (2018) relative to 2008, particularly as a result of IHBD. CONCLUSION: Incidence and mortality of PLC, and particularly IHBD, have continued to rise in England and Wales. Changes in the modes of diagnosis may be contributing.","Source":"PubMed","category":"HUMAN","training_data":"Incidence and mortality of primary liver cancer in England and Wales: changing patterns and ethnic variations AIM: To explore recent trends, modes of diagnosis, ethnic distribution and the mortality to incidence ratio of primary liver cancer by subtypes in England and Wales. METHODS: We obtained incidence (1979-2008) and mortality (1968-2008) data for primary liver cancer for England and Wales and calculated age-standardised incidence and mortality rates. Trends in age-standardised mortality (ASMR) and incidence (ASIR) rates and basis of diagnosis of primary liver cancer and subcategories: hepatocellular carcinoma, intrahepatic bile duct and unspecified liver tumours, were analysed over the study period. Changes in guidelines for the diagnosis of primary liver cancer (PLC) may impact changing trends in the rates that may be obtained. We thus explored changes in the mode of diagnosis as reported to cancer registries. Furthermore, we examined the distribution of these tumours by ethnicity. Most of the statistical manipulations of these data was carried out in Microsoft excel® (Seattle, Washington, United Sttaes). Additional epidemiological statistics were done in Epi Info software (Atlanta, GA, United Sttaes). To define patterns of change over time, we evaluated trends in ASMR and ASIR of PLC and intrahepatic bile duct carcinoma (IHBD) using a least squares regression line fitted to the natural logarithm of the mortality and incidence rates. We estimated the patterns of survival over subsequent 5 and 10 years using complement of mortality to incidence ratio (1-MIR). RESULTS: Age-standardised mortality rate of primary liver cancer increased in both sexes: from 2.56 and 1.29/100000 in 1968 to 5.10 and 2.63/100000 in 2008 for men and women respectively. The use of histology for diagnostic confirmation of primary liver cancer increased from 35.7% of registered cases in 1993 to plateau at about 50% during 2005 to 2008. Reliance on cytology as a basis of diagnosis has maintained a downward trend throughout the study period. Although approximately 30% of the PLC registrations had information on ethnicity, there was a relatively higher registration of the major tumour subtypes in patients whose ethnic backgrounds were from high incident regions of the world. Survival from PLC is estimated to get poorer in 10 years (2018) relative to 2008, particularly as a result of IHBD. CONCLUSION: Incidence and mortality of PLC, and particularly IHBD, have continued to rise in England and Wales. Changes in the modes of diagnosis may be contributing. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiology hepatocellular carcinoma intrahepatic cholangiocarcinoma hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc frequently occurring types primary liver cancer together among common incident cancers worldwide number modifiable nonmodifiable hcc icc risk factors reported review existing literature epidemiology risk factors hcc icc performed number major infectious lifestyle metabolic heritable risk factors hcc icc risk factors either potentially preventable eg alcohol tobacco use currently treatable eg hepatitis infection cases molecular pathway mechanism etiologic factors cause primary liver cancer well delineated however nearly cases believed given risk factor causes liver injury inflammation results chronic liver disease given rising prevalence several common hcc icc risk factors western world best opportunities improving care patients either prevention modifiable risk factors associated development chronic liver disease identification risk patients ensuring appropriately screened development primary liver cancer initiating treatment early pubmed","probabilities":0.9799733,"Title":"Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma","Abstract":"Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most frequently occurring types of primary liver cancer and together are among the most common incident cancers worldwide. There are a number of modifiable and nonmodifiable HCC and ICC risk factors that have been reported. A review of the existing literature the epidemiology and risk factors for HCC and ICC was performed. There are a number of major infectious, lifestyle, metabolic, and heritable risk factors for both HCC and ICC. Some of these risk factors are either potentially preventable (eg, alcohol and tobacco use) or are currently treatable (eg hepatitis infection). In most cases, the molecular pathway or mechanism by which these etiologic factors cause primary liver cancer has not been well delineated. However, in nearly all cases, it is believed that a given risk factor causes liver injury and inflammation which results in chronic liver disease. Given the rising prevalence of several common HCC and ICC risk factors in the western world, the best opportunities for improving the care of these patients are either through the prevention of modifiable risk factors that are associated with the development of chronic liver disease or the identification of at risk patients, ensuring they are appropriately screened for the development of primary liver cancer, and initiating treatment early.","Source":"PubMed","category":"HUMAN","training_data":"Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most frequently occurring types of primary liver cancer and together are among the most common incident cancers worldwide. There are a number of modifiable and nonmodifiable HCC and ICC risk factors that have been reported. A review of the existing literature the epidemiology and risk factors for HCC and ICC was performed. There are a number of major infectious, lifestyle, metabolic, and heritable risk factors for both HCC and ICC. Some of these risk factors are either potentially preventable (eg, alcohol and tobacco use) or are currently treatable (eg hepatitis infection). In most cases, the molecular pathway or mechanism by which these etiologic factors cause primary liver cancer has not been well delineated. However, in nearly all cases, it is believed that a given risk factor causes liver injury and inflammation which results in chronic liver disease. Given the rising prevalence of several common HCC and ICC risk factors in the western world, the best opportunities for improving the care of these patients are either through the prevention of modifiable risk factors that are associated with the development of chronic liver disease or the identification of at risk patients, ensuring they are appropriately screened for the development of primary liver cancer, and initiating treatment early. PubMed","prediction_labels":"HUMAN"},{"cleaned":"serum carbohydrate antigen ca 19 9 prognostic factor cholangiocarcinoma meta analysis study performed determine prognostic role preoperative serum carbohydrate antigen ca 19 9 levels survival patients cholangiocarcinoma articles published june 1 st 2010 evaluated preoperative ca19 9 levels prognosis cholangiocarcinoma collected meta analysis required information calculating individual relative risk rr extracted studies combined overall rr estimated nine eligible studies included one study dealt extra hepatic cholangiocarcinoma eight studies analyzed intra hepatic cholangiocarcinoma mean methodological quality score 74 1 ranging 65 5 82 5 overall rr nine studies 1 28 95 confidence interval 1 10 1 46 z score overall effect 13 83 p 0 001 association serum ca19 9 level lymph node involvement also assessed combined rr 1 471 95 confidence interval 0 411 5 264 z score overall effect 0 59 p 0 553 ca19 9 levels associated significantly prognosis patients cholangiocarcinoma meta analysis shows elevation preoperative ca19 9 levels correlated poor prognosis patients cholangiocarcinoma however larger scale randomized studies needed draw substantive conclusion pubmed","probabilities":0.9799733,"Title":"Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in cholangiocarcinoma: a meta-analysis","Abstract":"This study was performed to determine the prognostic role of preoperative serum carbohydrate antigen (CA) 19-9 levels in the survival of patients with cholangiocarcinoma. Articles published up to June 1(st), 2010 that evaluated preoperative CA19-9 levels and the prognosis of cholangiocarcinoma were collected for meta-analysis. The required information for calculating individual relative risk (RR) was extracted from the studies, and a combined overall RR was estimated. Nine eligible studies were included. One study dealt with extra-hepatic cholangiocarcinoma, while the other eight studies analyzed intra-hepatic cholangiocarcinoma. The mean methodological quality score was 74.1%, ranging from 65.5% to 82.5%. The overall RR for the nine studies was 1.28 (95% confidence interval = 1.10-1.46), and the Z-score for overall effect was 13.83 (P<0.001). The association between serum CA19-9 level and lymph node involvement was also assessed. The combined RR was 1.471 (95% confidence interval = 0.411-5.264) and Z-score for overall effect was 0.59 (P = 0.553). CA19-9 levels were associated significantly with the prognosis of patients with cholangiocarcinoma. This meta-analysis shows that elevation of preoperative CA19-9 levels is correlated with a poor prognosis of patients with cholangiocarcinoma. However, larger scale and randomized studies are needed to draw a more substantive conclusion.","Source":"PubMed","category":"HUMAN","training_data":"Serum carbohydrate antigen (CA) 19-9 as a prognostic factor in cholangiocarcinoma: a meta-analysis This study was performed to determine the prognostic role of preoperative serum carbohydrate antigen (CA) 19-9 levels in the survival of patients with cholangiocarcinoma. Articles published up to June 1(st), 2010 that evaluated preoperative CA19-9 levels and the prognosis of cholangiocarcinoma were collected for meta-analysis. The required information for calculating individual relative risk (RR) was extracted from the studies, and a combined overall RR was estimated. Nine eligible studies were included. One study dealt with extra-hepatic cholangiocarcinoma, while the other eight studies analyzed intra-hepatic cholangiocarcinoma. The mean methodological quality score was 74.1%, ranging from 65.5% to 82.5%. The overall RR for the nine studies was 1.28 (95% confidence interval = 1.10-1.46), and the Z-score for overall effect was 13.83 (P<0.001). The association between serum CA19-9 level and lymph node involvement was also assessed. The combined RR was 1.471 (95% confidence interval = 0.411-5.264) and Z-score for overall effect was 0.59 (P = 0.553). CA19-9 levels were associated significantly with the prognosis of patients with cholangiocarcinoma. This meta-analysis shows that elevation of preoperative CA19-9 levels is correlated with a poor prognosis of patients with cholangiocarcinoma. However, larger scale and randomized studies are needed to draw a more substantive conclusion. PubMed","prediction_labels":"HUMAN"},{"cleaned":"retrospective study gemcitabine cisplatin combination therapy second line treatment advanced biliary tract cancer background evaluate treatment outcome gemcitabine cisplatin combination therapy second line treatment advanced biliary tract cancer patients methods patients advanced biliary tract cancer refractory gemcitabine based first line chemotherapy treated gemcitabine cisplatin combination therapy gemcitabine 1 000 mg m 2 cisplatin 25 mg m 2 administered intravenously days 1 8 repeated every 3 weeks results sixty patients included tumor response disease control rates 1 7 58 3 respectively median overall survival time progression 6 7 months 95 ci 4 9 8 1 3 5 months 95 ci 2 5 5 0 respectively grade 3 4 toxicities included leucopenia 20 neutropenia 25 anemia 23 thrombocytopenia 17 nausea 2 anorexia 2 liver dysfunction 2 conclusions gemcitabine cisplatin combination therapy showed moderate efficacy safety second line treatment advanced biliary tract cancer refractory gemcitabine based first line chemotherapy pubmed","probabilities":0.9799733,"Title":"A retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer","Abstract":"BACKGROUND: To evaluate the treatment outcome of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer. PATIENTS AND METHODS: Patients with advanced biliary tract cancer who were refractory to gemcitabine-based first-line chemotherapy were treated with gemcitabine and cisplatin combination therapy. Gemcitabine (1,000 mg/m(2)) and cisplatin (25 mg/m(2)) were administered intravenously on days 1 and 8, repeated every 3 weeks. RESULTS: Sixty patients were included. The tumor response and disease control rates were 1.7 and 58.3%, respectively. The median overall survival and time to progression were 6.7 months (95% CI 4.9-8.1) and 3.5 months (95% CI 2.5-5.0), respectively. Grade 3/4 toxicities included leucopenia (20%), neutropenia (25%), anemia (23%), thrombocytopenia (17%), nausea (2%), anorexia (2%), and liver dysfunction (2%). CONCLUSIONS: Gemcitabine and cisplatin combination therapy showed moderate efficacy and safety as second-line treatment for advanced biliary tract cancer that is refractory to gemcitabine-based first-line chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"A retrospective study of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer BACKGROUND: To evaluate the treatment outcome of gemcitabine and cisplatin combination therapy as second-line treatment for advanced biliary tract cancer. PATIENTS AND METHODS: Patients with advanced biliary tract cancer who were refractory to gemcitabine-based first-line chemotherapy were treated with gemcitabine and cisplatin combination therapy. Gemcitabine (1,000 mg/m(2)) and cisplatin (25 mg/m(2)) were administered intravenously on days 1 and 8, repeated every 3 weeks. RESULTS: Sixty patients were included. The tumor response and disease control rates were 1.7 and 58.3%, respectively. The median overall survival and time to progression were 6.7 months (95% CI 4.9-8.1) and 3.5 months (95% CI 2.5-5.0), respectively. Grade 3/4 toxicities included leucopenia (20%), neutropenia (25%), anemia (23%), thrombocytopenia (17%), nausea (2%), anorexia (2%), and liver dysfunction (2%). CONCLUSIONS: Gemcitabine and cisplatin combination therapy showed moderate efficacy and safety as second-line treatment for advanced biliary tract cancer that is refractory to gemcitabine-based first-line chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison sixth seventh editions uicc classification perihilar cholangiocarcinoma background seventh edition tnm classification separates extrahepatic bile duct tumors perihilar distal tumors changes definition tnm classification impact seventh edition stage based prognostic prediction patients perihilar cholangiocarcinoma evaluated methods january 1998 march 2010 223 consecutive patients perihilar cholangiocarcinoma underwent surgery west german cancer center median survival times calculated 195 evaluable patients excluding hospital mortality separate classification sixth seventh editions results median overall survival increased patients classified using seventh compared sixth edition uicc 56 5 vs 23 75 months ii 45 9 vs 31 6 months iii 21 3 vs 8 76 months iv 7 03 vs 5 93 months category seventh edition alter median survival times t1 54 07 months t4 7 83 months cases median survival prolonged t2 patients 29 4 vs 31 6 months shortened t3 patients 19 43 vs 11 8 months staged using seventh edition according cox proportional hazards regression analysis patient survival better predicted seventh edition uicc stage pt categories p 0 0014 p 0 0396 respectively corresponding sixth edition categories p 0 4376 p 0 0926 respectively conclusions uicc seventh edition tnm classification perihilar cholangiocarcinoma improves separation patients intermediate stage tumors compared sixth edition prognostic value uicc staging system strengthened introduction seventh edition stn","probabilities":0.9799733,"Title":"Comparison Of The Sixth And The Seventh Editions Of The Uicc Classification For Perihilar Cholangiocarcinoma","Abstract":"Background: The seventh edition of the TNM classification separates extrahepatic bile duct tumors into perihilar and distal tumors and further changes the definition of the TNM classification. The impact of the seventh edition on stage-based prognostic prediction for patients with perihilar cholangiocarcinoma was evaluated. \r\n\r\n Methods: Between January 1998 and March 2010, 223 consecutive patients with perihilar cholangiocarcinoma underwent surgery at the West German Cancer Center. Median survival times were calculated for the 195 evaluable patients (excluding those with in-hospital mortality) after separate classification by both sixth and seventh editions. \r\n\r\n Results: Median overall survival was increased in patients classified using the seventh compared with the sixth edition (UICC I: 56.5 vs 23.75 months; II: 45.9 vs 31.6 months; III: 21.3 vs. 8.76 months; IV: 7.03 vs 5.93 months). The T category of the seventh edition did not alter median survival times of T1 (54.07 months) and T4 (7.83 months) cases, but median survival was prolonged for T2 patients (29.4 vs 31.6 months), and shortened for T3 patients (19.43 vs 11.8 months) staged using the seventh edition. According to Cox proportional hazards regression analysis, patient survival was better predicted by the seventh edition UICC stage and pT categories (p=0.0014 and p=0.0396, respectively), than the corresponding sixth edition categories (p=0.4376 and p=0.0926, respectively). \r\n\r\n Conclusions: The UICC seventh edition TNM classification for perihilar cholangiocarcinoma improves separation of patients with intermediate stage tumors compared with the sixth edition. The prognostic value of the UICC staging system has been strengthened by the introduction of the seventh edition.","Source":"STN","category":"HUMAN","training_data":"Comparison Of The Sixth And The Seventh Editions Of The Uicc Classification For Perihilar Cholangiocarcinoma Background: The seventh edition of the TNM classification separates extrahepatic bile duct tumors into perihilar and distal tumors and further changes the definition of the TNM classification. The impact of the seventh edition on stage-based prognostic prediction for patients with perihilar cholangiocarcinoma was evaluated. \r\n\r\n Methods: Between January 1998 and March 2010, 223 consecutive patients with perihilar cholangiocarcinoma underwent surgery at the West German Cancer Center. Median survival times were calculated for the 195 evaluable patients (excluding those with in-hospital mortality) after separate classification by both sixth and seventh editions. \r\n\r\n Results: Median overall survival was increased in patients classified using the seventh compared with the sixth edition (UICC I: 56.5 vs 23.75 months; II: 45.9 vs 31.6 months; III: 21.3 vs. 8.76 months; IV: 7.03 vs 5.93 months). The T category of the seventh edition did not alter median survival times of T1 (54.07 months) and T4 (7.83 months) cases, but median survival was prolonged for T2 patients (29.4 vs 31.6 months), and shortened for T3 patients (19.43 vs 11.8 months) staged using the seventh edition. According to Cox proportional hazards regression analysis, patient survival was better predicted by the seventh edition UICC stage and pT categories (p=0.0014 and p=0.0396, respectively), than the corresponding sixth edition categories (p=0.4376 and p=0.0926, respectively). \r\n\r\n Conclusions: The UICC seventh edition TNM classification for perihilar cholangiocarcinoma improves separation of patients with intermediate stage tumors compared with the sixth edition. The prognostic value of the UICC staging system has been strengthened by the introduction of the seventh edition. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic value retrieved lymph node counts patients node negative perihilar cholangiocarcinomas background study aimed find prognostic value optimal cut value retrieved lymph node ln counts patients node negative perihilar cholangiocarcinomas methods surveillance epidemiology end results seer database used screen patients perihilar cholangiocarcinoma cut number retrieved lns determined x tile programme kaplan meier methods log rank tests cox regression analysis used survival analysis results total 778 patients perihilar cholangiocarcinoma 2004 2014 met inclusion criteria research 403 patients without ln metastases n0 among cut numbers retrieved lns determined using x tile programme 8 18 results univariate multivariate survival analyses n0 patients showed patients 18 retrieved lns significantly better survival rate patients 1 7 retrieved lns patients 8 17 retrieved lns subgroup patients early stage tumours patients least 13 retrieved lns significantly better overall cancer specific survival patients fewer retrieved lns conclusions retrieved ln counts independent prognostic factor patients node negative perihilar cholangiocarcinoma patients least 18 retrieved lns better overall cancer specific survival patients fewer retrieved lns minimum requirement retrieving lns reach 18 perihilar cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic value of retrieved lymph node counts in patients with node-negative perihilar cholangiocarcinomas","Abstract":"BACKGROUND: This study aimed to find out the prognostic value and optimal cut-off value of retrieved lymph node (LN) counts in patients with node-negative perihilar cholangiocarcinomas. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to screen out patients with perihilar cholangiocarcinoma. The cut-off number of retrieved LNs was determined by the X-tile programme. Kaplan-Meier methods with log-rank tests and Cox regression analysis were used for survival analysis. RESULTS: A total of 778 patients with perihilar cholangiocarcinoma (2004-2014) met the inclusion criteria for this research, and there were 403 patients without LN metastases (N0) among them. The cut-off numbers of retrieved LNs, which were determined using the X-tile programme, were 8 and 18. Both results of univariate and multivariate survival analyses in N0 patients showed that patients with ≥18 retrieved LNs had a significantly better survival rate than patients with 1-7 retrieved LNs and patients with 8-17 retrieved LNs. In the subgroup of patients with early-stage tumours, patients with at least 13 retrieved LNs had a significantly better overall and cancer-specific survival than patients with fewer retrieved LNs. CONCLUSIONS: The retrieved LN counts are an independent prognostic factor for patients with node-negative perihilar cholangiocarcinoma. Patients with at least 18 retrieved LNs had a better overall and cancer-specific survival than patients with fewer retrieved LNs. The minimum requirement for retrieving of LNs should reach 18 in perihilar cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic value of retrieved lymph node counts in patients with node-negative perihilar cholangiocarcinomas BACKGROUND: This study aimed to find out the prognostic value and optimal cut-off value of retrieved lymph node (LN) counts in patients with node-negative perihilar cholangiocarcinomas. METHODS: The Surveillance, Epidemiology and End Results (SEER) database was used to screen out patients with perihilar cholangiocarcinoma. The cut-off number of retrieved LNs was determined by the X-tile programme. Kaplan-Meier methods with log-rank tests and Cox regression analysis were used for survival analysis. RESULTS: A total of 778 patients with perihilar cholangiocarcinoma (2004-2014) met the inclusion criteria for this research, and there were 403 patients without LN metastases (N0) among them. The cut-off numbers of retrieved LNs, which were determined using the X-tile programme, were 8 and 18. Both results of univariate and multivariate survival analyses in N0 patients showed that patients with ≥18 retrieved LNs had a significantly better survival rate than patients with 1-7 retrieved LNs and patients with 8-17 retrieved LNs. In the subgroup of patients with early-stage tumours, patients with at least 13 retrieved LNs had a significantly better overall and cancer-specific survival than patients with fewer retrieved LNs. CONCLUSIONS: The retrieved LN counts are an independent prognostic factor for patients with node-negative perihilar cholangiocarcinoma. Patients with at least 18 retrieved LNs had a better overall and cancer-specific survival than patients with fewer retrieved LNs. The minimum requirement for retrieving of LNs should reach 18 in perihilar cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radical operation hilar cholangiocarcinoma comparable eastern western centers outcome analysis prognostic factors background extensive resection hilar cholangiocarcinoma effective treatment high morbidity poor prognosis remain concerns previous data shown marked differences outcomes comparable eastern western centers compared outcomes management hilar cholangiocarcinoma one japanese one british institution comparable experience methods 298 consecutive patients hilar cholangiocarcinoma evaluated hirosaki university hospital japan st james university hospital leeds uk 183 underwent radical resection clinicopathologic variables postoperative outcomes compared results significant differences observed hirosaki leeds cohorts overall outcomes despite several differences patient characteristics although difference 90 day mortality 2 5 vs 13 6 respectively disease specific 5 year survival rates 32 8 31 9 respectively p 767 multivariate analysis identified trisectionectomy odds ratio 2 32 p 010 combined pancreatoduodenectomy odds ratio 7 88 p 010 perioperative blood transfusion odds ratio 1 88 p 045 associated postoperative major complications preoperative biliary drainage associated postoperative major complications preoperative biliary drainage risk ratio 2 21 p 018 perioperative blood transfusion risk ratio 1 58 p 029 lymph node metastasis risk ratio 2 00 p 002 moderate poorly differentiated tumor risk ratio 1 72 p 029 microvascular invasion risk ratio 1 63 p 046 r1 resection risk ratio 1 90 p 005 risk factors poor survival conclusion disease specific survival prognostic factors similar centers meticulous operative technique avoid perioperative blood transfusion may improve long term survival pubmed","probabilities":0.9799733,"Title":"Radical operation for hilar cholangiocarcinoma in comparable Eastern and Western centers: Outcome analysis and prognostic factors","Abstract":"BACKGROUND: Extensive resection for hilar cholangiocarcinoma is the most effective treatment, but high morbidity and poor prognosis remain concerns. Previous data have shown marked differences in outcomes between comparable Eastern and Western centers. We compared the outcomes of the management for hilar cholangiocarcinoma at one Japanese and one British institution with comparable experience. METHODS: Of 298 consecutive patients with hilar cholangiocarcinoma evaluated at Hirosaki University Hospital, Japan and St. James's University Hospital, Leeds, UK, 183 underwent radical resection. Clinicopathologic variables and postoperative outcomes were compared. RESULTS: Significant differences were not observed between the Hirosaki and Leeds cohorts in overall outcomes despite several differences in the patient characteristics. Although there was a difference in 90-day mortality (2.5% vs 13.6%, respectively), disease-specific 5-year survival rates were 32.8% and 31.9%, respectively (P = .767). Multivariate analysis identified trisectionectomy (odds ratio = 2.32; P = .010), combined pancreatoduodenectomy (odds ratio = 7.88; P = .010), and perioperative blood transfusion (odds ratio = 1.88; P = .045) were associated with postoperative major complications, while preoperative biliary drainage associated with postoperative major complications, while preoperative biliary drainage (risk ratio = 2.21; P = .018), perioperative blood transfusion (risk ratio = 1.58; P = .029), lymph node metastasis (risk ratio = 2.00; P = .002), moderate/poorly differentiated tumor (risk ratio = 1.72; P = .029), microvascular invasion (risk ratio = 1.63; P = .046), and R1 resection (risk ratio = 1.90; P = .005) were risk factors for poor survival. CONCLUSION: Disease-specific survival and prognostic factors were similar in both centers. Meticulous operative technique to avoid perioperative blood transfusion may improve long-term survival.","Source":"PubMed","category":"HUMAN","training_data":"Radical operation for hilar cholangiocarcinoma in comparable Eastern and Western centers: Outcome analysis and prognostic factors BACKGROUND: Extensive resection for hilar cholangiocarcinoma is the most effective treatment, but high morbidity and poor prognosis remain concerns. Previous data have shown marked differences in outcomes between comparable Eastern and Western centers. We compared the outcomes of the management for hilar cholangiocarcinoma at one Japanese and one British institution with comparable experience. METHODS: Of 298 consecutive patients with hilar cholangiocarcinoma evaluated at Hirosaki University Hospital, Japan and St. James's University Hospital, Leeds, UK, 183 underwent radical resection. Clinicopathologic variables and postoperative outcomes were compared. RESULTS: Significant differences were not observed between the Hirosaki and Leeds cohorts in overall outcomes despite several differences in the patient characteristics. Although there was a difference in 90-day mortality (2.5% vs 13.6%, respectively), disease-specific 5-year survival rates were 32.8% and 31.9%, respectively (P = .767). Multivariate analysis identified trisectionectomy (odds ratio = 2.32; P = .010), combined pancreatoduodenectomy (odds ratio = 7.88; P = .010), and perioperative blood transfusion (odds ratio = 1.88; P = .045) were associated with postoperative major complications, while preoperative biliary drainage associated with postoperative major complications, while preoperative biliary drainage (risk ratio = 2.21; P = .018), perioperative blood transfusion (risk ratio = 1.58; P = .029), lymph node metastasis (risk ratio = 2.00; P = .002), moderate/poorly differentiated tumor (risk ratio = 1.72; P = .029), microvascular invasion (risk ratio = 1.63; P = .046), and R1 resection (risk ratio = 1.90; P = .005) were risk factors for poor survival. CONCLUSION: Disease-specific survival and prognostic factors were similar in both centers. Meticulous operative technique to avoid perioperative blood transfusion may improve long-term survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"early recurrence following pancreaticoduodenectomy patients ampullary cancer aimed identify factors early recurrence within 6 months ampullary cancer following curative resection compare immunohistochemical expression rate various antibodies 2 main histologic subtypes ampullary adenocarcinoma retrospective study postoperative outcomes clinicopathologic factors early recurrence occurred 14 93 patients underwent pancreaticoduodenectomy pd ampullary adenocarcinoma january 2002 august 2014 analyzed thereafter identified factors associated early recurrence following surgery additionally compared expression rates ck7 ck20 muc1 muc2 muc5ac muc6 s100p cdx2 2 main histologic subtypes ampullary adenocarcinoma ncc2019 0138 patients underwent pd ampullary cancer divided 2 groups early recurrence others compared patients 14 patients 32 6 developed early recurrence shorter median disease free survival 4 2 vs 49 7 months p 001 overall survival 18 2 vs 113 7 months p 001 large tumor lymph node metastasis pancreatobiliary type independently associated early recurrence ampullary cancer following pd large tumor lymph node metastasis pancreatobiliary type independent risk factors early recurrence ampullary cancer following curative resection therefore ampullary cancer patients factors considered receive aggressive adjuvant treatment frequent post operative follow pubmed","probabilities":0.9799733,"Title":"Very early recurrence following pancreaticoduodenectomy in patients with ampullary cancer","Abstract":"We aimed to identify the factors for very early recurrence (within 6 months) of ampullary cancer following curative resection and to compare the immunohistochemical expression rate of various antibodies between the 2 main histologic subtypes of ampullary adenocarcinoma.In this retrospective study, the postoperative outcomes and clinicopathologic factors for very early recurrence that occurred in 14 of 93 patients who underwent pancreaticoduodenectomy (PD) for ampullary adenocarcinoma between January 2002 and August 2014 were analyzed. Thereafter, we identified the factors associated with very early recurrence following surgery. Additionally, we compared the expression rates of CK7, CK20, MUC1, MUC2, MUC5AC, MUC6, S100P, and CDX2 between the 2 main histologic subtypes of ampullary adenocarcinoma (NCC2019-0138).The patients who underwent PD for ampullary cancer were divided into 2 groups: very early recurrence and others. Compared with the other patients, the 14 patients (32.6%) who developed very early recurrence had shorter median disease-free survival (4.2 vs 49.7 months, P = .001) and overall survival (18.2 vs 113.7 months, P < .001). Large tumor, lymph node metastasis, and pancreatobiliary type were independently associated with very early recurrence of ampullary cancer following PD.Large tumor, lymph node metastasis, and pancreatobiliary type were the independent risk factors for very early recurrence of ampullary cancer following curative resection. Therefore, ampullary cancer patients with these factors should be considered to receive aggressive adjuvant treatment and frequent post-operative follow-up.","Source":"PubMed","category":"HUMAN","training_data":"Very early recurrence following pancreaticoduodenectomy in patients with ampullary cancer We aimed to identify the factors for very early recurrence (within 6 months) of ampullary cancer following curative resection and to compare the immunohistochemical expression rate of various antibodies between the 2 main histologic subtypes of ampullary adenocarcinoma.In this retrospective study, the postoperative outcomes and clinicopathologic factors for very early recurrence that occurred in 14 of 93 patients who underwent pancreaticoduodenectomy (PD) for ampullary adenocarcinoma between January 2002 and August 2014 were analyzed. Thereafter, we identified the factors associated with very early recurrence following surgery. Additionally, we compared the expression rates of CK7, CK20, MUC1, MUC2, MUC5AC, MUC6, S100P, and CDX2 between the 2 main histologic subtypes of ampullary adenocarcinoma (NCC2019-0138).The patients who underwent PD for ampullary cancer were divided into 2 groups: very early recurrence and others. Compared with the other patients, the 14 patients (32.6%) who developed very early recurrence had shorter median disease-free survival (4.2 vs 49.7 months, P = .001) and overall survival (18.2 vs 113.7 months, P < .001). Large tumor, lymph node metastasis, and pancreatobiliary type were independently associated with very early recurrence of ampullary cancer following PD.Large tumor, lymph node metastasis, and pancreatobiliary type were the independent risk factors for very early recurrence of ampullary cancer following curative resection. Therefore, ampullary cancer patients with these factors should be considered to receive aggressive adjuvant treatment and frequent post-operative follow-up. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiology cholangiocarcinoma united states incidence mortality trends background cholangiocarcinoma aggressive malignancy available studies assessing incidence mortality study aim investigate trends incidence mortality large nation wide epidemiologic study methods used seer 18 database study cholangiocarcinoma cases us 2000 2015 incidence mortality rates cholangiocarcinoma calculated race expressed 1 000 000 person years annual percent change apc calculated using joinpoint regression software results reviewed 16 189 patients cholangiocarcinoma 64 4 intrahepatic patients whites 78 4 males 51 3 older 65 years 63 total 13 121 patients died cholangiocarcinoma study period cholangiocarcinoma incidence mortality 11 977 10 295 higher among asians males individuals older 65 years incidence rates significantly increased study period apc 5 063 p 001 mortality increased significantly study period apc 5 964 p 001 decreased 2013 apc 25 029 p 001 conclusion incidence mortality cholangiocarcinoma increasing study period significant observed disparities based race gender google scholar","probabilities":0.9799733,"Title":"Epidemiology Of Cholangiocarcinoma; United States Incidence And Mortality Trends","Abstract":"Background\nCholangiocarcinoma is an aggressive malignancy with few available studies assessing incidence and mortality. In this study, we aim to investigate trends of incidence and mortality in a large nation-wide epidemiologic study.\nMethods\nWe used SEER 18 database to study cholangiocarcinoma cases in the US during 2000-2015. Incidence and mortality rates of cholangiocarcinoma were calculated by race and were expressed by 1,000,000 person-years. Annual percent change (APC) was calculated using joinpoint regression software.\nResults\nWe reviewed 16,189 patients with cholangiocarcinoma, of which 64.4% were intrahepatic. Most patients were whites (78.4%), males (51.3%), and older than 65 years (63%). A total of 13,121 patients died of cholangiocarcinoma during the study period. Cholangiocarcinoma incidence and mortality were 11.977 and 10.295 and were both higher among Asians, males, and individuals older than 65 years. Incidence rates have significantly increased over the study period (APC = 5.063%, P < .001), while mortality increased significantly over the study period (APC = 5.964%, P < .001), but decreased after 2013 (APC = −25.029, P < .001).\nConclusion\nThe incidence and mortality of cholangiocarcinoma were increasing in the study period with significant observed disparities based on race and gender.","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology Of Cholangiocarcinoma; United States Incidence And Mortality Trends Background\nCholangiocarcinoma is an aggressive malignancy with few available studies assessing incidence and mortality. In this study, we aim to investigate trends of incidence and mortality in a large nation-wide epidemiologic study.\nMethods\nWe used SEER 18 database to study cholangiocarcinoma cases in the US during 2000-2015. Incidence and mortality rates of cholangiocarcinoma were calculated by race and were expressed by 1,000,000 person-years. Annual percent change (APC) was calculated using joinpoint regression software.\nResults\nWe reviewed 16,189 patients with cholangiocarcinoma, of which 64.4% were intrahepatic. Most patients were whites (78.4%), males (51.3%), and older than 65 years (63%). A total of 13,121 patients died of cholangiocarcinoma during the study period. Cholangiocarcinoma incidence and mortality were 11.977 and 10.295 and were both higher among Asians, males, and individuals older than 65 years. Incidence rates have significantly increased over the study period (APC = 5.063%, P < .001), while mortality increased significantly over the study period (APC = 5.964%, P < .001), but decreased after 2013 (APC = −25.029, P < .001).\nConclusion\nThe incidence and mortality of cholangiocarcinoma were increasing in the study period with significant observed disparities based on race and gender. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"coffee consumption risk hepatocellular carcinoma intrahepatic cholangiocarcinoma sex liver cancer pooling project background coffee consumption reported inversely associated hepatocellular carcinoma hcc common type liver cancer caffeine chemopreventive properties whether caffeine responsible coffee hcc association well studied addition studies examined relationship sex studies examined whether association coffee intrahepatic cholangiocarcinoma icc second common type liver cancer methods liver cancer pooling project consortium u based cohort studies data 1 212 893 individuals hcc n 860 icc n 260 nine cohorts pooled multivariable adjusted hazard ratios hr 95 confidence intervals ci estimated using proportional hazards regression results higher coffee consumption associated lower risk hcc hr 3 cups day vs non drinker 0 73 95 ci 0 53 0 99 ptrend cups day 0 0001 notable reduced risk seen among women men pinteraction 0 07 women consumed three cups coffee per day 54 lower risk hcc hr 0 46 95 ci 0 26 0 81 whereas men modest reduced risk hcc hr 0 93 95 ci 0 63 1 37 associations stronger caffeinated coffee hr 3 cups day vs non drinker 0 71 95 ci 0 50 1 01 decaffeinated coffee hr 0 92 95 ci 0 55 1 54 association coffee consumption icc conclusions findings suggest u population coffee consumption associated reduced risk hcc impact research specific coffee compounds mechanisms may account associations needed pubmed","probabilities":0.9799733,"Title":"Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project","Abstract":"BACKGROUND: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. METHODS: In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression. RESULTS: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; Ptrend cups/day = <0.0001). More notable reduced risk was seen among women than men (Pinteraction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no association between coffee consumption and ICC. CONCLUSIONS: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. IMPACT: Further research into specific coffee compounds and mechanisms that may account for these associations is needed.","Source":"PubMed","category":"HUMAN","training_data":"Coffee Consumption and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma by Sex: The Liver Cancer Pooling Project BACKGROUND: Coffee consumption has been reported to be inversely associated with hepatocellular carcinoma (HCC), the most common type of liver cancer. Caffeine has chemopreventive properties, but whether caffeine is responsible for the coffee-HCC association is not well studied. In addition, few studies have examined the relationship by sex, and no studies have examined whether there is an association between coffee and intrahepatic cholangiocarcinoma (ICC), the second most common type of liver cancer. METHODS: In the Liver Cancer Pooling Project, a consortium of U.S.-based cohort studies, data from 1,212,893 individuals (HCC, n = 860; ICC, n = 260) in nine cohorts were pooled. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using proportional hazards regression. RESULTS: Higher coffee consumption was associated with lower risk of HCC (HR>3 cups/day vs. non-drinker, 0.73; 95% CI, 0.53-0.99; Ptrend cups/day = <0.0001). More notable reduced risk was seen among women than men (Pinteraction = 0.07). Women who consumed more than three cups of coffee per day were at a 54% lower risk of HCC (HR, 0.46; 95% CI, 0.26-0.81), whereas men had more modest reduced risk of HCC (HR, 0.93; 95% CI, 0.63-1.37). The associations were stronger for caffeinated coffee (HR>3 cups/day vs. non-drinker, 0.71; 95% CI, 0.50-1.01) than decaffeinated coffee (HR, 0.92; 95% CI, 0.55-1.54). There was no association between coffee consumption and ICC. CONCLUSIONS: These findings suggest that, in a U.S. population, coffee consumption is associated with reduced risk of HCC. IMPACT: Further research into specific coffee compounds and mechanisms that may account for these associations is needed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"crossroad obesity gastric cancer obesity reached epidemic proportions worldwide disproportionate prevalence different communities ethnic groups recently american medical association recognized obesity disease significant milestone opens possibilities treating obesity standardized health plans obesity inflammatory disease characterized elevated levels biomarkers associated abnormal lipid profiles glucose levels blood pressure lead onset metabolic syndrome interestingly inflammatory biomarkers particular implicated risk developing several types cancer likewise obesity linked esophageal breast gallbladder kidney pancreatic colorectal cancers thus exists link obesity status tumor appearance may associated differential levels circulating profiles several inflammatory molecules example mediators inflammatory responses obesity gastric cancer risk pro inflammatory molecules produced activated cells infiltrating inflamed tissues molecules trigger pathways activation shared obesity cancer therefore understanding different pathways modulated help reduce impact diseases concomitant existence society pubmed","probabilities":0.88235295,"Title":"At the crossroad between obesity and gastric cancer","Abstract":"Obesity has reached epidemic proportions worldwide with disproportionate prevalence in different communities and ethnic groups. Recently, the American Medical Association recognized obesity as a disease, which is a significant milestone that opens the possibilities of treating obesity under standardized health plans. Obesity is an inflammatory disease characterized by elevated levels of biomarkers associated with abnormal lipid profiles, glucose levels, and blood pressure that lead to the onset of metabolic syndrome. Interestingly, inflammatory biomarkers, in particular, have been implicated in the risk of developing several types of cancer. Likewise, obesity has been linked to esophageal, breast, gallbladder, kidney, pancreatic, and colorectal cancers. Thus, there exists a link between obesity status and tumor appearance, which may be associated to the differential levels and the circulating profiles of several inflammatory molecules. For example, mediators of the inflammatory responses in both obesity and gastric cancer risk are the same: pro-inflammatory molecules produced by the activated cells infiltrating the inflamed tissues. These molecules trigger pathways of activation shared by obesity and cancer. Therefore, understanding how these different pathways are modulated would help reduce the impact that both diseases, and their concomitant existence, have on society.","Source":"PubMed","category":"HUMAN","training_data":"At the crossroad between obesity and gastric cancer Obesity has reached epidemic proportions worldwide with disproportionate prevalence in different communities and ethnic groups. Recently, the American Medical Association recognized obesity as a disease, which is a significant milestone that opens the possibilities of treating obesity under standardized health plans. Obesity is an inflammatory disease characterized by elevated levels of biomarkers associated with abnormal lipid profiles, glucose levels, and blood pressure that lead to the onset of metabolic syndrome. Interestingly, inflammatory biomarkers, in particular, have been implicated in the risk of developing several types of cancer. Likewise, obesity has been linked to esophageal, breast, gallbladder, kidney, pancreatic, and colorectal cancers. Thus, there exists a link between obesity status and tumor appearance, which may be associated to the differential levels and the circulating profiles of several inflammatory molecules. For example, mediators of the inflammatory responses in both obesity and gastric cancer risk are the same: pro-inflammatory molecules produced by the activated cells infiltrating the inflamed tissues. These molecules trigger pathways of activation shared by obesity and cancer. Therefore, understanding how these different pathways are modulated would help reduce the impact that both diseases, and their concomitant existence, have on society. PubMed","prediction_labels":"HUMAN"},{"cleaned":"bloodstream infections patients solid tumors epidemiology antibiotic therapy outcomes 528 episodes single cancer center current information regarding bloodstream infection bsi patients solid tumors scarce assessed epidemiology antibiotic therapy outcomes bsi patients also compared patients died survived identify risk factors associated mortality january 2006 july 2012 episodes bsi patients solid tumors cancer center prospectively recorded analyzed total 528 episodes bsi documented 489 patients frequent neoplasms hepatobiliary tumors 19 followed lung cancer 18 lower gastrointestinal malignancies 16 many patients received corticosteroid therapy 41 15 neutropenia 500 neutrophils l time bsi common source bsi cholangitis 21 followed abdominal 19 5 urinary tract infections 17 gram negative bsi occurred 55 cases mainly due escherichia coli 55 pseudomonas aeruginosa 18 klebsiella pneumoniae 16 among gram positive bsi 35 viridans group streptococci frequent causative organisms 22 followed staphylococcus aureus 21 enterococcus species 18 identified 61 multidrug resistant mdr organisms 13 mainly extended spectrum lactamase producing enterobacteriaceae n 20 ampc producing enterobacteriaceae n 13 majority patients bsi caused mdr organisms received antibiotics 70 previously hospitalized 61 4 frequently patients bsi caused susceptible strains inadequate empirical antibiotic therapy given 23 patients higher proportion bsi due mdr strain 69 early 48 h overall 30 d case fatality rates 7 32 respectively overall case fatality rate higher among cases caused mdr organisms 39 3 independent risk factors early case fatality rate endogenous source bsi odds ratio 3 57 95 confidence interval ci 1 06 12 02 shock presentation 3 63 95 ci 1 63 8 09 corticosteroid therapy 3 245 95 ci 1 43 7 32 independent risk factors overall case fatality rate presence chronic advanced cancer 35 39 95 ci 2 48 504 91 shock presentation 25 84 95 ci 3 73 179 0 corticosteroid therapy 6 98 95 ci 1 61 30 21 bsi patients solid tumors occurred mainly among hepatobiliary cancer cholangitis frequent source gram negative bacilli frequent causative agents mdr organisms relatively common particularly patients previously received antibiotics hospitalized patients frequently treated inadequate empirical antibiotic therapy poorer outcome case fatality rate patients solid tumors bsi high associated chronic advanced cancer corticosteroid therapy shock presentation pubmed","probabilities":0.9799733,"Title":"Bloodstream infections in patients with solid tumors: epidemiology, antibiotic therapy, and outcomes in 528 episodes in a single cancer center","Abstract":"Current information regarding bloodstream infection (BSI) in patients with solid tumors is scarce. We assessed the epidemiology, antibiotic therapy, and outcomes of BSI in these patients. We also compared patients who died with those who survived to identify risk factors associated with mortality. From January 2006 to July 2012 all episodes of BSI in patients with solid tumors at a cancer center were prospectively recorded and analyzed. A total of 528 episodes of BSI were documented in 489 patients. The most frequent neoplasms were hepatobiliary tumors (19%), followed by lung cancer (18%) and lower gastrointestinal malignancies (16%). Many patients had received corticosteroid therapy (41%), and 15% had neutropenia (<500 neutrophils/μL) at the time of BSI. The most common source of BSI was cholangitis (21%), followed by other abdominal (19.5%) and urinary tract infections (17%). Gram-negative BSI occurred in 55% of cases, mainly due to Escherichia coli (55%), Pseudomonas aeruginosa (18%), and Klebsiella pneumoniae (16%). Among gram-positive BSI (35%), viridans group streptococci were the most frequent causative organisms (22%), followed by Staphylococcus aureus (21%) and Enterococcus species (18%). We identified 61 multidrug-resistant (MDR) organisms (13%), mainly extended-spectrum β-lactamase-producing Enterobacteriaceae (n = 20) and AmpC-producing Enterobacteriaceae (n = 13). The majority of patients with BSI caused by MDR organisms had received antibiotics (70%), and they had been previously hospitalized (61.4%) more frequently than patients with BSI caused by susceptible strains. Inadequate empirical antibiotic therapy was given to 23% of patients, with a higher proportion in those with BSI due to a MDR strain (69%). Early (<48 h) and overall (30 d) case-fatality rates were 7% and 32%, respectively. The overall case-fatality rate was higher among cases caused by MDR organisms (39.3%). The only independent risk factors for the early case-fatality rate were the endogenous source of BSI (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.06-12.02), shock at presentation (OR, 3.63; 95% CI, 1.63-8.09), and corticosteroid therapy (OR, 3.245; 95% CI, 1.43-7.32). The independent risk factors for overall case-fatality rate were the presence of a chronic advanced cancer (OR, 35.39; 95% CI, 2.48-504.91), shock at presentation (OR, 25.84; 95% CI, 3.73-179.0), and corticosteroid therapy (OR, 6.98; 95% CI, 1.61-30.21).BSI in patients with solid tumors occurred mainly among those with hepatobiliary cancer, and cholangitis was the most frequent source; gram-negative bacilli were the most frequent causative agents. MDR organisms were relatively common, particularly in patients who had previously received antibiotics and had been hospitalized; these patients were frequently treated with inadequate empirical antibiotic therapy and had a poorer outcome. The case-fatality rate of patients with solid tumors and BSI was high and was associated with chronic advanced cancer, corticosteroid therapy, and shock at presentation.","Source":"PubMed","category":"HUMAN","training_data":"Bloodstream infections in patients with solid tumors: epidemiology, antibiotic therapy, and outcomes in 528 episodes in a single cancer center Current information regarding bloodstream infection (BSI) in patients with solid tumors is scarce. We assessed the epidemiology, antibiotic therapy, and outcomes of BSI in these patients. We also compared patients who died with those who survived to identify risk factors associated with mortality. From January 2006 to July 2012 all episodes of BSI in patients with solid tumors at a cancer center were prospectively recorded and analyzed. A total of 528 episodes of BSI were documented in 489 patients. The most frequent neoplasms were hepatobiliary tumors (19%), followed by lung cancer (18%) and lower gastrointestinal malignancies (16%). Many patients had received corticosteroid therapy (41%), and 15% had neutropenia (<500 neutrophils/μL) at the time of BSI. The most common source of BSI was cholangitis (21%), followed by other abdominal (19.5%) and urinary tract infections (17%). Gram-negative BSI occurred in 55% of cases, mainly due to Escherichia coli (55%), Pseudomonas aeruginosa (18%), and Klebsiella pneumoniae (16%). Among gram-positive BSI (35%), viridans group streptococci were the most frequent causative organisms (22%), followed by Staphylococcus aureus (21%) and Enterococcus species (18%). We identified 61 multidrug-resistant (MDR) organisms (13%), mainly extended-spectrum β-lactamase-producing Enterobacteriaceae (n = 20) and AmpC-producing Enterobacteriaceae (n = 13). The majority of patients with BSI caused by MDR organisms had received antibiotics (70%), and they had been previously hospitalized (61.4%) more frequently than patients with BSI caused by susceptible strains. Inadequate empirical antibiotic therapy was given to 23% of patients, with a higher proportion in those with BSI due to a MDR strain (69%). Early (<48 h) and overall (30 d) case-fatality rates were 7% and 32%, respectively. The overall case-fatality rate was higher among cases caused by MDR organisms (39.3%). The only independent risk factors for the early case-fatality rate were the endogenous source of BSI (odds ratio [OR], 3.57; 95% confidence interval [CI], 1.06-12.02), shock at presentation (OR, 3.63; 95% CI, 1.63-8.09), and corticosteroid therapy (OR, 3.245; 95% CI, 1.43-7.32). The independent risk factors for overall case-fatality rate were the presence of a chronic advanced cancer (OR, 35.39; 95% CI, 2.48-504.91), shock at presentation (OR, 25.84; 95% CI, 3.73-179.0), and corticosteroid therapy (OR, 6.98; 95% CI, 1.61-30.21).BSI in patients with solid tumors occurred mainly among those with hepatobiliary cancer, and cholangitis was the most frequent source; gram-negative bacilli were the most frequent causative agents. MDR organisms were relatively common, particularly in patients who had previously received antibiotics and had been hospitalized; these patients were frequently treated with inadequate empirical antibiotic therapy and had a poorer outcome. The case-fatality rate of patients with solid tumors and BSI was high and was associated with chronic advanced cancer, corticosteroid therapy, and shock at presentation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"conization marker persistent cervical human papillomavirus hpv infection risk gastrointestinal cancer danish 34 year nationwide cohort study purpose persistent cervical infection human papillomavirus hpv may marker poor immune function thus associated increased cancer risk hpv infection implicated cases cervical cancer except anal esophageal cancers association persistent hpv infection gastrointestinal cancer investigated methods performed nationwide population based cohort study 83 008 women undergoing cervical conization 1978 2011 using cervical conization marker chronic hpv infection computed standardized incidence ratios sirs measure relative risk cancer comparing women undergoing conization expected general population also calculated absolute risks results follow 988 gi cancers occurred versus 880 expected among 83 008 women followed median 14 9 years corresponding sir 1 1 95 ci 1 1 1 2 risks increased anal sir 2 9 95 ci 2 3 3 5 esophageal sir 1 5 95 ci 1 1 2 0 cancers suggested increased risks cancers gallbladder biliary tract sir 1 3 95 ci 0 90 1 8 pancreas sir 1 2 95 ci 0 97 1 4 liver sir 1 1 95 ci 0 79 1 6 sirs decreased increasing follow time risks gastric small intestinal colon rectal cancers elevated overall absolute cancer risk 0 18 95 ci 0 15 0 21 5 years conclusions relative risks several gastrointestinal cancers raised among women underwent cervical conization persistent hpv infection absolute risks low pubmed","probabilities":0.8684211,"Title":"Conization as a marker of persistent cervical human papillomavirus (HPV) infection and risk of gastrointestinal cancer: a Danish 34-year nationwide cohort study","Abstract":"PURPOSE: Persistent cervical infection with human papillomavirus (HPV) may be a marker of poor immune function and thus associated with an increased cancer risk. HPV infection is implicated in all cases of cervical cancer, but except for anal and esophageal cancers, the association between persistent HPV infection and gastrointestinal cancer has not been investigated. METHODS: We performed a nationwide population-based cohort study of 83,008 women undergoing cervical conization between 1978 and 2011, using cervical conization as a marker of chronic HPV infection. We computed standardized incidence ratios (SIRs) as a measure of the relative risk of each cancer comparing women undergoing conization with that expected in the general population. We also calculated absolute risks. RESULTS: During follow-up, 988 GI cancers occurred versus 880 expected among 83,008 women followed for a median of 14.9 years, corresponding to a SIR of 1.1 (95 % CI 1.1-1.2). Risks were increased for anal (SIR 2.9; 95 % CI 2.3-3.5) and esophageal (SIR 1.5; 95 % CI 1.1-2.0) cancers, with suggested increased risks of cancers of the gallbladder and biliary tract (SIR 1.3; 95 % CI 0.90-1.8), pancreas (SIR 1.2; 95 % CI 0.97-1.4), and liver (SIR 1.1; 95 % CI 0.79-1.6). The SIRs decreased with increasing follow-up time. The risks of gastric, small intestinal, colon, or rectal cancers were not elevated. Overall, the absolute cancer risk was 0.18 % (95 % CI 0.15-0.21) after 5 years. CONCLUSIONS: The relative risks of several gastrointestinal cancers were raised among women who underwent cervical conization for persistent HPV infection, but the absolute risks were low.","Source":"PubMed","category":"HUMAN","training_data":"Conization as a marker of persistent cervical human papillomavirus (HPV) infection and risk of gastrointestinal cancer: a Danish 34-year nationwide cohort study PURPOSE: Persistent cervical infection with human papillomavirus (HPV) may be a marker of poor immune function and thus associated with an increased cancer risk. HPV infection is implicated in all cases of cervical cancer, but except for anal and esophageal cancers, the association between persistent HPV infection and gastrointestinal cancer has not been investigated. METHODS: We performed a nationwide population-based cohort study of 83,008 women undergoing cervical conization between 1978 and 2011, using cervical conization as a marker of chronic HPV infection. We computed standardized incidence ratios (SIRs) as a measure of the relative risk of each cancer comparing women undergoing conization with that expected in the general population. We also calculated absolute risks. RESULTS: During follow-up, 988 GI cancers occurred versus 880 expected among 83,008 women followed for a median of 14.9 years, corresponding to a SIR of 1.1 (95 % CI 1.1-1.2). Risks were increased for anal (SIR 2.9; 95 % CI 2.3-3.5) and esophageal (SIR 1.5; 95 % CI 1.1-2.0) cancers, with suggested increased risks of cancers of the gallbladder and biliary tract (SIR 1.3; 95 % CI 0.90-1.8), pancreas (SIR 1.2; 95 % CI 0.97-1.4), and liver (SIR 1.1; 95 % CI 0.79-1.6). The SIRs decreased with increasing follow-up time. The risks of gastric, small intestinal, colon, or rectal cancers were not elevated. Overall, the absolute cancer risk was 0.18 % (95 % CI 0.15-0.21) after 5 years. CONCLUSIONS: The relative risks of several gastrointestinal cancers were raised among women who underwent cervical conization for persistent HPV infection, but the absolute risks were low. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pathology cholangiocellular carcinoma cholangiocellular carcinoma ccc malignant tumor harboring poor prognosis occurring liver gallbladder extra intrahepatic biliary ducts article reviews topic concerning ccc point view surgical pathologist paper deals classification ccc intrahepatic peripheral hilar extrahepatic subtype different morphology molecular features prognosis together classical gross pathology histopathology natural history ccc hilar extrahepatic ccc share biological characteristics pancreatic ductal adenocarcinoma review comprises various types precancerous lesions biliary tract summarizes updates 8th edition tnm classification describes routine issues concerning histopathological diagnostics ccc including immunohistochemistry frozen section methods pubmed","probabilities":0.9799733,"Title":"Pathology of cholangiocellular carcinoma","Abstract":"Cholangiocellular carcinoma (CCC) is a malignant tumor harboring a poor prognosis, occurring in the liver, gallbladder and in extra- or intrahepatic biliary ducts. The article reviews the topic concerning CCC from the point of view of a surgical pathologist. The paper deals with classification of CCC into an intrahepatic/peripheral and hilar/extrahepatic subtype with different morphology, molecular features and prognosis; together with classical gross pathology, histopathology and natural history of CCC. Hilar and extrahepatic CCC share some biological characteristics with pancreatic ductal adenocarcinoma. The review comprises various types of precancerous lesions of biliary tract, summarizes updates in 8th edition of TNM classification and describes the routine issues concerning histopathological diagnostics of CCC, including immunohistochemistry and frozen section methods.","Source":"PubMed","category":"HUMAN","training_data":"Pathology of cholangiocellular carcinoma Cholangiocellular carcinoma (CCC) is a malignant tumor harboring a poor prognosis, occurring in the liver, gallbladder and in extra- or intrahepatic biliary ducts. The article reviews the topic concerning CCC from the point of view of a surgical pathologist. The paper deals with classification of CCC into an intrahepatic/peripheral and hilar/extrahepatic subtype with different morphology, molecular features and prognosis; together with classical gross pathology, histopathology and natural history of CCC. Hilar and extrahepatic CCC share some biological characteristics with pancreatic ductal adenocarcinoma. The review comprises various types of precancerous lesions of biliary tract, summarizes updates in 8th edition of TNM classification and describes the routine issues concerning histopathological diagnostics of CCC, including immunohistochemistry and frozen section methods. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival line therapy older patients advanced biliary tract cancer btc background overall survival os advanced metastatic btc adequately described outside clinical trial setting real world descriptions os line therapy including patients receive systemic chemotherapy widely available study used data recent cohort us patients available seer medicare linked database examine os diagnosis advanced metastatic btc well initiation first second line treatment methods patients advanced metastatic btc diagnosed 2010 2013 identified seer medicare follow 2014 demographic clinical characteristics analyzed kaplan meier estimator used describe os diagnosis among patients os diagnosis among patients receive systemic treatment os line treatment date treatment initiation cox proportional hazards model used identify demographic clinical factors associated survival results 1 461 eligible patients aged 66 years 39 gallbladder 22 intrahepatic 22 extrahepatic 9 ampulla vater cancer two thirds patients stage iv disease 38 patients n 558 received systemic chemotherapy systemic treatment patients somewhat younger likely white stage iv cancer less likely mobility limitations 24 vs 38 patients receive systemic treatment among patients unadjusted median os diagnosis 5 6 months 95 ci 5 0 6 1 among patients treated unadjusted median survival 3 3 months n 903 95 ci 2 8 4 0 diagnosis os evaluated line treatment median os 8 2 months n 558 95 ci 7 6 9 0 first line initiation 5 6 months n 220 95 ci 4 6 6 5 second line initiation conclusions among newly diagnosed older us patients less half receive systemic treatment advanced btc outcomes among treated untreated patients remain poor immediate need better therapies treat patients advanced btc google scholar","probabilities":0.9799733,"Title":"Survival By Line Of Therapy Of Older Patients With Advanced Biliary Tract Cancer (Btc)","Abstract":"Background: Overall survival (OS) in advanced or metastatic BTC has not been adequately described outside the clinical trial setting. Further, real-world descriptions of OS by line of therapy, including in patients who do not receive systemic chemotherapy, are not widely available. In this study, we used data from a recent cohort of US patients available in the SEER-Medicare linked database to examine OS from diagnosis of advanced or metastatic BTC as well as from initiation of first- and second-line treatment. Methods: Patients with advanced or metastatic BTC diagnosed between 2010 and 2013 were identified in SEER-Medicare, with follow-up through 2014. Demographic and clinical characteristics were analyzed. The Kaplan-Meier estimator was used to describe OS from diagnosis among all patients, OS from diagnosis among patients who did not receive systemic treatment, and OS by line of treatment, from date of treatment initiation. The Cox proportional hazards model was used to identify demographic and clinical factors associated with survival. Results: Of the 1,461 eligible patients aged ≥66 years, 39% had gallbladder, 22% had intrahepatic, 22% had extrahepatic, and 9% had ampulla of Vater cancer. More than two-thirds of patients had stage IV disease, and 38% of patients (n = 558) received systemic chemotherapy. Systemic treatment patients were somewhat younger, more likely to be white, have stage IV cancer and less likely to have mobility limitations (24% vs. 38%) than patients who did not receive systemic treatment. Among all patients, unadjusted median OS from diagnosis was 5.6 months (95% CI 5.0-6.1). Among patients who were not treated, unadjusted median survival was 3.3 months (n = 903; 95% CI 2.8-4.0) from diagnosis. When OS was evaluated by line of treatment, median OS was 8.2 months (n = 558; 95% CI 7.6-9.0) from first-line initiation and 5.6 months (n = 220; 95% CI 4.6-6.5) from second-line initiation. Conclusions: Among newly diagnosed, older US patients, less than half receive systemic treatment for their advanced BTC, and outcomes among both treated and untreated patients remain poor. There is an immediate need for better therapies to treat patients with advanced BTC.","Source":"Google Scholar","category":"HUMAN","training_data":"Survival By Line Of Therapy Of Older Patients With Advanced Biliary Tract Cancer (Btc) Background: Overall survival (OS) in advanced or metastatic BTC has not been adequately described outside the clinical trial setting. Further, real-world descriptions of OS by line of therapy, including in patients who do not receive systemic chemotherapy, are not widely available. In this study, we used data from a recent cohort of US patients available in the SEER-Medicare linked database to examine OS from diagnosis of advanced or metastatic BTC as well as from initiation of first- and second-line treatment. Methods: Patients with advanced or metastatic BTC diagnosed between 2010 and 2013 were identified in SEER-Medicare, with follow-up through 2014. Demographic and clinical characteristics were analyzed. The Kaplan-Meier estimator was used to describe OS from diagnosis among all patients, OS from diagnosis among patients who did not receive systemic treatment, and OS by line of treatment, from date of treatment initiation. The Cox proportional hazards model was used to identify demographic and clinical factors associated with survival. Results: Of the 1,461 eligible patients aged ≥66 years, 39% had gallbladder, 22% had intrahepatic, 22% had extrahepatic, and 9% had ampulla of Vater cancer. More than two-thirds of patients had stage IV disease, and 38% of patients (n = 558) received systemic chemotherapy. Systemic treatment patients were somewhat younger, more likely to be white, have stage IV cancer and less likely to have mobility limitations (24% vs. 38%) than patients who did not receive systemic treatment. Among all patients, unadjusted median OS from diagnosis was 5.6 months (95% CI 5.0-6.1). Among patients who were not treated, unadjusted median survival was 3.3 months (n = 903; 95% CI 2.8-4.0) from diagnosis. When OS was evaluated by line of treatment, median OS was 8.2 months (n = 558; 95% CI 7.6-9.0) from first-line initiation and 5.6 months (n = 220; 95% CI 4.6-6.5) from second-line initiation. Conclusions: Among newly diagnosed, older US patients, less than half receive systemic treatment for their advanced BTC, and outcomes among both treated and untreated patients remain poor. There is an immediate need for better therapies to treat patients with advanced BTC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"patients advanced cancer biliary obstruction benefit biliary stenting analysis prognostic factors background patients advanced cancer may present obstructive jaundice biliary stenting treatment choice however patients benefit well defined yet aim delineate clinical factors affecting prognosis material methods charts 140 patients advanced cancer underwent biliary stenting retrospectively analyzed median age 63 5 years patients 73 52 1 male 32 22 9 ecog ps 1 81 57 9 ps 2 frequent cancer types cholangiocellular cancer 64 45 7 pancreatic cancer 36 25 7 results median overall survival os 141 95 ci 100 7 185 3 days female patients lived longer 161 0 vs 124 0 days p 0 036 patients colorectal cancer lived longest 667 0 days followed cholangiocellular 211 0 days gastric cancers 106 0 days p 0 004 distribution primary diagnosis differed significantly sexes cholangiocellular cancer present 22 30 1 73 men 42 62 7 67 women chi square p 0 001 trend longer overall survival alt p 0 08 ast p 0 06 normalized stent insertion 137 patients 63 45 5 experience complication 74 patients complications 39 28 5 episodes cholangitic infections 35 25 5 biliary obstructions three patients find data infections conclusion underlying malignancy hence natural biology therapeutic expectations probably important factors must considered decision making pubmed","probabilities":0.9799733,"Title":"Which patients with advanced cancer and biliary obstruction benefit from biliary stenting most? An analysis of prognostic factors","Abstract":"BACKGROUND: Patients with advanced cancer may present with obstructive jaundice. Biliary stenting is the treatment of choice. However, which patients benefit most is not well-defined, yet. Our aim was to delineate the clinical factors affecting prognosis. MATERIAL AND METHODS: Charts of 140 patients with advanced cancer who underwent biliary stenting were retrospectively analyzed. Their median age was 63.5 years. Of these patients, 73 (52.1 %) were male, 32 (22.9 %) had ECOG PS 1 and 81 (57.9 %) had PS 2. The most frequent cancer types were cholangiocellular cancer (64, 45.7 %) and pancreatic cancer (36, 25.7 %). RESULTS: Median overall survival (OS) was 141 (95 % CI, 100.7-185.3) days. Female patients lived longer (161.0 vs. 124.0 days) (p = 0.036). Those patients with colorectal cancer lived the longest (667.0 days), followed by cholangiocellular (211.0 days), and gastric cancers (106.0 days) (p = 0.004). The distribution of primary diagnosis differed significantly between sexes: cholangiocellular cancer was present in 22 (30.1 %) out of 73 men and 42(62.7 %) out of 67 women (chi-square p < 0.001). There was a trend for longer overall survival if ALT (p = 0.08) and AST (p = 0.06) were normalized after stent insertion. Of the 137 patients, 63 (45.5 %) did not experience any complication. In 74 patients with complications, there were 39 (28.5 %) episodes of cholangitic infections and 35 (25.5 %) biliary obstructions. In three patients, we could not find data on infections. CONCLUSION: Underlying malignancy, hence the natural biology and the therapeutic expectations are probably the most important factors which must be considered during decision-making.","Source":"PubMed","category":"HUMAN","training_data":"Which patients with advanced cancer and biliary obstruction benefit from biliary stenting most? An analysis of prognostic factors BACKGROUND: Patients with advanced cancer may present with obstructive jaundice. Biliary stenting is the treatment of choice. However, which patients benefit most is not well-defined, yet. Our aim was to delineate the clinical factors affecting prognosis. MATERIAL AND METHODS: Charts of 140 patients with advanced cancer who underwent biliary stenting were retrospectively analyzed. Their median age was 63.5 years. Of these patients, 73 (52.1 %) were male, 32 (22.9 %) had ECOG PS 1 and 81 (57.9 %) had PS 2. The most frequent cancer types were cholangiocellular cancer (64, 45.7 %) and pancreatic cancer (36, 25.7 %). RESULTS: Median overall survival (OS) was 141 (95 % CI, 100.7-185.3) days. Female patients lived longer (161.0 vs. 124.0 days) (p = 0.036). Those patients with colorectal cancer lived the longest (667.0 days), followed by cholangiocellular (211.0 days), and gastric cancers (106.0 days) (p = 0.004). The distribution of primary diagnosis differed significantly between sexes: cholangiocellular cancer was present in 22 (30.1 %) out of 73 men and 42(62.7 %) out of 67 women (chi-square p < 0.001). There was a trend for longer overall survival if ALT (p = 0.08) and AST (p = 0.06) were normalized after stent insertion. Of the 137 patients, 63 (45.5 %) did not experience any complication. In 74 patients with complications, there were 39 (28.5 %) episodes of cholangitic infections and 35 (25.5 %) biliary obstructions. In three patients, we could not find data on infections. CONCLUSION: Underlying malignancy, hence the natural biology and the therapeutic expectations are probably the most important factors which must be considered during decision-making. PubMed","prediction_labels":"HUMAN"},{"cleaned":"non alcoholic fatty liver disease risk factor cholangiocarcinoma systematic review meta analysis background non alcoholic fatty liver disease nafld recently identified risk factor gastrointestinal tract cancers especially hepatocellular carcinoma colorectal cancer whether nafld risk factor cholangiocarcinoma cca remains inconclusive aim study determine potential association nafld cca stratifying subtypes intrahepatic cca icca extrahepatic cca ecca methods search conducted relevant studies published april 2017 using medline embase scopus cochrane databases odds ratio adjusted 95 confidence interval ci estimated using random effects model subgroup analyses conducted study characteristics results seven case control studies included analysis total 9 102 cca patients 5 067 icca 4 035 ecca 129 111 controls overall nafld associated increased risk cca pooled 1 95 95 ci 1 36 2 79 2 76 classified subtypes nafld associated icca ecca ors 2 22 95 ci 1 52 3 24 2 67 1 55 95 ci 1 03 2 33 2 69 respectively overall pooled adjusted ors 1 97 95 ci 1 41 2 75 2 71 2 09 95 ci 1 49 2 91 2 42 2 05 95 ci 1 59 2 64 2 0 ccas icca ecca respectively conclusions meta analysis suggests nafld may potentially increase risk cca development magnitude nafld cca risk greater icca ecca subtype suggestive common pathogenesis icca hepatocellular carcinoma studies confirm association warranted trial registration protocol study registered prospero international prospective register systematic reviews crd42016046573 pubmed","probabilities":0.9799733,"Title":"Non-alcoholic fatty liver disease as a risk factor for cholangiocarcinoma: a systematic review and meta-analysis","Abstract":"BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been recently identified as a risk factor of gastrointestinal tract cancers, especially hepatocellular carcinoma, and colorectal cancer. Whether NAFLD is a risk factor for cholangiocarcinoma (CCA) remains inconclusive. The aim of this study is to determine a potential association between NAFLD and CCA, stratifying by its subtypes; intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA). METHODS: A search was conducted for relevant studies published up to April 2017 using MEDLINE, EMBASE, Scopus and Cochrane databases. Odds ratio (OR) and adjusted OR with 95% confidence interval (CI) were estimated using a random-effects model. Subgroup analyses were conducted with study characteristics. RESULTS: Seven case-control studies were included in the analysis, with a total of 9,102 CCA patients (5,067 iCCA and 4,035 eCCA) and 129,111 controls. Overall, NAFLD was associated with an increased risk for CCA, with pooled OR of 1.95 (95%CI: 1.36-2.79, I (2) =76%). When classified by subtypes, NAFLD was associated with both iCCA and eCCA, with ORs of 2.22 (95%CI: 1.52-3.24, I (2) =67%) and 1.55 (95%CI: 1.03-2.33, I (2) =69%), respectively. The overall pooled adjusted ORs were 1.97 (95%CI: 1.41-2.75, I (2) =71%), 2.09 (95%CI, 1.49-2.91, I (2) =42%) and 2.05 (95%CI, 1.59-2.64, I (2) =0%) for all CCAs, iCCA, and eCCA, respectively. CONCLUSIONS: This meta-analysis suggests that NAFLD may potentially increase the risk of CCA development. The magnitude of NAFLD on CCA risk is greater for iCCA than eCCA subtype, suggestive of a common pathogenesis of iCCA and hepatocellular carcinoma. Further studies to confirm this association are warranted. TRIAL REGISTRATION: The protocol for this study was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016046573).","Source":"PubMed","category":"HUMAN","training_data":"Non-alcoholic fatty liver disease as a risk factor for cholangiocarcinoma: a systematic review and meta-analysis BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been recently identified as a risk factor of gastrointestinal tract cancers, especially hepatocellular carcinoma, and colorectal cancer. Whether NAFLD is a risk factor for cholangiocarcinoma (CCA) remains inconclusive. The aim of this study is to determine a potential association between NAFLD and CCA, stratifying by its subtypes; intrahepatic CCA (iCCA), and extrahepatic CCA (eCCA). METHODS: A search was conducted for relevant studies published up to April 2017 using MEDLINE, EMBASE, Scopus and Cochrane databases. Odds ratio (OR) and adjusted OR with 95% confidence interval (CI) were estimated using a random-effects model. Subgroup analyses were conducted with study characteristics. RESULTS: Seven case-control studies were included in the analysis, with a total of 9,102 CCA patients (5,067 iCCA and 4,035 eCCA) and 129,111 controls. Overall, NAFLD was associated with an increased risk for CCA, with pooled OR of 1.95 (95%CI: 1.36-2.79, I (2) =76%). When classified by subtypes, NAFLD was associated with both iCCA and eCCA, with ORs of 2.22 (95%CI: 1.52-3.24, I (2) =67%) and 1.55 (95%CI: 1.03-2.33, I (2) =69%), respectively. The overall pooled adjusted ORs were 1.97 (95%CI: 1.41-2.75, I (2) =71%), 2.09 (95%CI, 1.49-2.91, I (2) =42%) and 2.05 (95%CI, 1.59-2.64, I (2) =0%) for all CCAs, iCCA, and eCCA, respectively. CONCLUSIONS: This meta-analysis suggests that NAFLD may potentially increase the risk of CCA development. The magnitude of NAFLD on CCA risk is greater for iCCA than eCCA subtype, suggestive of a common pathogenesis of iCCA and hepatocellular carcinoma. Further studies to confirm this association are warranted. TRIAL REGISTRATION: The protocol for this study was registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42016046573). PubMed","prediction_labels":"HUMAN"},{"cleaned":"porcelain gallbladder benign process concern malignancy background gallbladder wall calcifications otherwise known porcelain gallbladder received considerable attention due perceived association gallbladder carcinoma perception strong correlation persists recent reports raise conceivable doubts study design systematic literature search conducted human studies describing gallbladder wall calcification association gallbladder malignancy results 111 articles met inclusion criteria identified 340 patients gallbladder wall calcification 340 patients 72 21 diagnosed malignancy gallbladder examining subgroup 13 studies n 124 without obvious selection bias rate gallbladder malignancy 6 0 33 compared 1 0 4 matched cohort patients without gallbladder wall calcification p 0 036 relative risk 8 0 95 ci 1 0 63 0 multivariate analysis identified presence symptoms typical gallbladder cancer odds ratio 83 6 95 ci 2 3 2979 1 p 0 015 presence gallbladder mass odds ratio 3226 6 95 ci 17 2 603884 8 p 0 003 independent prognostic factors harboring gallbladder malignancy conclusions risk harboring gallbladder cancer patients gallbladder wall calcifications lower recently anticipated risk factors identified limited clinical value since stigmatic advanced gallbladder cancer absence better risk stratification presence relative low rate associated malignancy prophylactic cholecystectomy appears appropriate otherwise healthy patients whereas non operative approach considered patients significant co morbidity pubmed","probabilities":0.8684211,"Title":"Porcelain gallbladder: a benign process or concern for malignancy?","Abstract":"BACKGROUND: Gallbladder wall calcifications, otherwise known as porcelain gallbladder, have received considerable attention due to its perceived association with gallbladder carcinoma. While the perception of a strong correlation persists, more recent reports raise conceivable doubts. STUDY DESIGN: A systematic literature search was conducted of human studies describing gallbladder wall calcification and its association with gallbladder malignancy. RESULTS: The 111 articles which met inclusion criteria identified 340 patients with gallbladder wall calcification. Of the 340 patients, 72 (21 %) were diagnosed with malignancy of the gallbladder. When examining a subgroup of 13 studies (n = 124) without obvious selection bias, the rate of gallbladder malignancy was only 6 % (0-33 %) compared to 1 % (0-4 %) in a matched cohort of patients without gallbladder wall calcification (p = 0.036, relative risk 8.0 (95%CI 1.0-63.0)). Multivariate analysis identified the presence of symptoms typical for gallbladder cancer (odds ratio 83.6, 95%CI 2.3-2979.1, p = 0.015) and the presence of a gallbladder mass (odds ratio 3226.6, 95%CI 17.2-603884.8, p = 0.003) as the only independent prognostic factors for harboring gallbladder malignancy. CONCLUSIONS: The risk of harboring gallbladder cancer in patients with gallbladder wall calcifications is lower than recently anticipated. The risk factors identified have only limited clinical value, since they are stigmatic for advanced gallbladder cancer. In the absence of better risk stratification and in the presence of a relative low rate of associated malignancy, prophylactic cholecystectomy appears appropriate for otherwise healthy patients; whereas a non-operative approach should be considered in patients with significant co-morbidity.","Source":"PubMed","category":"HUMAN","training_data":"Porcelain gallbladder: a benign process or concern for malignancy? BACKGROUND: Gallbladder wall calcifications, otherwise known as porcelain gallbladder, have received considerable attention due to its perceived association with gallbladder carcinoma. While the perception of a strong correlation persists, more recent reports raise conceivable doubts. STUDY DESIGN: A systematic literature search was conducted of human studies describing gallbladder wall calcification and its association with gallbladder malignancy. RESULTS: The 111 articles which met inclusion criteria identified 340 patients with gallbladder wall calcification. Of the 340 patients, 72 (21 %) were diagnosed with malignancy of the gallbladder. When examining a subgroup of 13 studies (n = 124) without obvious selection bias, the rate of gallbladder malignancy was only 6 % (0-33 %) compared to 1 % (0-4 %) in a matched cohort of patients without gallbladder wall calcification (p = 0.036, relative risk 8.0 (95%CI 1.0-63.0)). Multivariate analysis identified the presence of symptoms typical for gallbladder cancer (odds ratio 83.6, 95%CI 2.3-2979.1, p = 0.015) and the presence of a gallbladder mass (odds ratio 3226.6, 95%CI 17.2-603884.8, p = 0.003) as the only independent prognostic factors for harboring gallbladder malignancy. CONCLUSIONS: The risk of harboring gallbladder cancer in patients with gallbladder wall calcifications is lower than recently anticipated. The risk factors identified have only limited clinical value, since they are stigmatic for advanced gallbladder cancer. In the absence of better risk stratification and in the presence of a relative low rate of associated malignancy, prophylactic cholecystectomy appears appropriate for otherwise healthy patients; whereas a non-operative approach should be considered in patients with significant co-morbidity. PubMed","prediction_labels":"HUMAN"},{"cleaned":"predictive factors treatment outcome patients advanced biliary tract cancer receiving gemcitabine plus cisplatin first line chemotherapy background studies clearly identified prognostic factors patients advanced biliary tract cancer btc receiving gemcitabine plus cisplatin gc acknowledged standard chemotherapy regimen objectives aim study identify predictive factors overall survival os advanced btc patients receiving gc therapy methods data 307 patients advanced btc received gc therapy first line chemotherapy institution january 2007 june 2017 reviewed retrospectively patients randomly assigned investigation validation dataset ratio 2 1 multivariate analysis conducted identify prognostic factors prognostic index proposed investigation dataset usefulness index confirmed validation dataset results multivariate analysis identified poor performance status elevated serum lactate dehydrogenase elevated neutrophil lymphocyte ratio independent unfavorable predictors patients classified three groups according factors found outcomes differed significantly among three groups p 0 0002 good vs intermediate prognosis groups p 0 005 intermediate vs poor prognosis groups index applied validation dataset os confirmed differ significantly among three groups p 0 04 good vs intermediate prognosis groups p 0 0001 intermediate vs poor prognosis groups conclusions identified three predictors os patients advanced btc receiving gc therapy study based classify patients three risk groups stn","probabilities":0.9799733,"Title":"Predictive Factors Of The Treatment Outcome In Patients With Advanced Biliary Tract Cancer Receiving Gemcitabine Plus Cisplatin As First-Line Chemotherapy","Abstract":"Background: Few studies have clearly identified the prognostic factors in patients with advanced biliary tract cancer (BTC) receiving gemcitabine plus cisplatin (GC) which is acknowledged as standard chemotherapy regimen. \r\n\r\n Objectives: The aim of this study was to identify predictive factors of the overall survival (OS) in advanced BTC patients receiving GC therapy. \r\n\r\n Methods: Data of 307 patients with advanced BTC who received GC therapy as the first-line chemotherapy at our institution from January 2007 to June 2017 were reviewed retrospectively. The patients were randomly assigned to the investigation or the validation dataset at the ratio of 2:1. Multivariate analysis was conducted to identify the prognostic factors, a prognostic index is proposed from the investigation dataset, and the usefulness of this index was confirmed in the validation dataset. \r\n\r\n Results: Multivariate analysis identified poor performance status, elevated serum lactate dehydrogenase, and elevated neutrophil-to-lymphocyte ratio as independent unfavorable predictors. The patients could be classified into three groups according to these factors, and it was found that the outcomes differed significantly among the three groups (P = 0.0002, good- vs. intermediate-prognosis groups; P = 0.005, intermediate- vs. poor-prognosis groups). When this index was applied to the validation dataset, the OS was confirmed to differ significantly among the three groups (P = 0.04, good- vs. intermediate-prognosis groups, P < 0.0001, intermediate- vs. poor-prognosis groups). \r\n\r\n Conclusions: We identified three predictors of the OS in patients with advanced BTC receiving GC therapy in this study, based on which we could classify the patients into three risk groups.","Source":"STN","category":"HUMAN","training_data":"Predictive Factors Of The Treatment Outcome In Patients With Advanced Biliary Tract Cancer Receiving Gemcitabine Plus Cisplatin As First-Line Chemotherapy Background: Few studies have clearly identified the prognostic factors in patients with advanced biliary tract cancer (BTC) receiving gemcitabine plus cisplatin (GC) which is acknowledged as standard chemotherapy regimen. \r\n\r\n Objectives: The aim of this study was to identify predictive factors of the overall survival (OS) in advanced BTC patients receiving GC therapy. \r\n\r\n Methods: Data of 307 patients with advanced BTC who received GC therapy as the first-line chemotherapy at our institution from January 2007 to June 2017 were reviewed retrospectively. The patients were randomly assigned to the investigation or the validation dataset at the ratio of 2:1. Multivariate analysis was conducted to identify the prognostic factors, a prognostic index is proposed from the investigation dataset, and the usefulness of this index was confirmed in the validation dataset. \r\n\r\n Results: Multivariate analysis identified poor performance status, elevated serum lactate dehydrogenase, and elevated neutrophil-to-lymphocyte ratio as independent unfavorable predictors. The patients could be classified into three groups according to these factors, and it was found that the outcomes differed significantly among the three groups (P = 0.0002, good- vs. intermediate-prognosis groups; P = 0.005, intermediate- vs. poor-prognosis groups). When this index was applied to the validation dataset, the OS was confirmed to differ significantly among the three groups (P = 0.04, good- vs. intermediate-prognosis groups, P < 0.0001, intermediate- vs. poor-prognosis groups). \r\n\r\n Conclusions: We identified three predictors of the OS in patients with advanced BTC receiving GC therapy in this study, based on which we could classify the patients into three risk groups. STN","prediction_labels":"HUMAN"},{"cleaned":"platynosomum fastosum induced cholangiocarcinomas cats platynosomum fastosum feline biliary tract trematode generally causes asymptomatic infections early 1980s brazil p fastosum associated cholangiocarcinomas finding confirmed various publications parasite last 30 years study aims report three cases cholangiocarcinomas cats associated presence p fastosum 2000 2011 veterinary hospital federal university campina grande northeast brazil 348 cats necropsied 11 3 16 parasitized p fastosum three cases resulted death associated cholangiocarcinomas found associated p fastosum histologically tumors consisted acini composed cells pleomorphic nuclei loose chromatin evident nucleoli lightly eosinophilic cytoplasm metastases observed two cases first case involved metastases lungs kidneys ovary peritoneum second case lymph nodes kidneys heart encephalon involved 8 cats died causes parasite incidental finding cases histologic lesions nonsuppurative cholangiohepatitis periductal fibrosis p fastosum present six animals also showed pre neoplastic changes hyperplasia dysplasia biliary duct epithelium study concluded observed human biliary tract trematodes p fastosum causes cholangiocarcinomas liver cats stn","probabilities":1.0,"Title":"Platynosomum Fastosum-Induced Cholangiocarcinomas In Cats","Abstract":"Platynosomum fastosum is a feline biliary tract trematode that generally causes asymptomatic infections. In the early 1980s in Brazil, P. fastosum was associated with cholangiocarcinomas, but this finding was not confirmed in the various publications on the parasite during the last 30 years. This study aims to report three cases of cholangiocarcinomas in cats associated with the presence of P. fastosum. From 2000 to 2011, in the Veterinary Hospital of the Federal University of Campina Grande in northeast Brazil, 348 cats were necropsied, 11 of which (3.16%) were parasitized by P. fastosum. Three cases that resulted in death were associated with cholangiocarcinomas that were found to be associated with P. fastosum. Histologically, the tumors consisted of acini composed of cells with pleomorphic nuclei, loose chromatin, evident nucleoli and lightly eosinophilic cytoplasm. Metastases were observed in two cases. The first case involved metastases to the lungs, kidneys, ovary and peritoneum, and in the second case, the lymph nodes, kidneys, heart and encephalon were involved. The other 8 cats died from other causes, and the parasite was an incidental finding. In those cases, the histologic lesions were nonsuppurative cholangiohepatitis and periductal fibrosis with P. fastosum present. Six animals also showed pre-neoplastic changes (hyperplasia and dysplasia) of the biliary duct epithelium. The study concluded that, as observed in other human biliary tract trematodes, P. fastosum causes cholangiocarcinomas in the liver of cats.","Source":"STN","category":"ANIMAL","training_data":"Platynosomum Fastosum-Induced Cholangiocarcinomas In Cats Platynosomum fastosum is a feline biliary tract trematode that generally causes asymptomatic infections. In the early 1980s in Brazil, P. fastosum was associated with cholangiocarcinomas, but this finding was not confirmed in the various publications on the parasite during the last 30 years. This study aims to report three cases of cholangiocarcinomas in cats associated with the presence of P. fastosum. From 2000 to 2011, in the Veterinary Hospital of the Federal University of Campina Grande in northeast Brazil, 348 cats were necropsied, 11 of which (3.16%) were parasitized by P. fastosum. Three cases that resulted in death were associated with cholangiocarcinomas that were found to be associated with P. fastosum. Histologically, the tumors consisted of acini composed of cells with pleomorphic nuclei, loose chromatin, evident nucleoli and lightly eosinophilic cytoplasm. Metastases were observed in two cases. The first case involved metastases to the lungs, kidneys, ovary and peritoneum, and in the second case, the lymph nodes, kidneys, heart and encephalon were involved. The other 8 cats died from other causes, and the parasite was an incidental finding. In those cases, the histologic lesions were nonsuppurative cholangiohepatitis and periductal fibrosis with P. fastosum present. Six animals also showed pre-neoplastic changes (hyperplasia and dysplasia) of the biliary duct epithelium. The study concluded that, as observed in other human biliary tract trematodes, P. fastosum causes cholangiocarcinomas in the liver of cats. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic factors patients middle distal bile duct cancers aim identify influence surgery type prognostic factors middle distal bile duct cancers methods august 1990 june 2011 data regarding clinicopathological factors 194 patients surgical pathological confirmation collected total 133 patients underwent resections r0 r1 r2 n 102 24 7 whereas 61 patients underwent nonresectional surgery either pancreaticoduodenectomy pd bile duct resection bdr selected according sites tumors co morbidities patients confirming resection margin frozen histology cases univariate multivariate analyses clinicopathologic factors performed utilizing kaplan meyer method cox hazard regression analysis results overall 5 year survival rate 133 patients underwent resection r0 r1 r2 41 2 whereas patients survived longer 3 years among 61 patient underwent nonresectional surgeries 5 year survival rate patients underwent pd n 90 higher rate underwent bdr n 43 although difference statistically significant 46 6 vs 30 0 p 0 105 however pd higher rate r0 resection bdr 90 0 vs 48 8 p 0 0001 r0 resection achieved pd bdr showed similar survival rates 49 4 vs 46 5 p 0 762 5 year survival rates r0 r1 resections significantly different 49 0 vs 21 0 p 0 132 r2 resections lower survival 0 p 0 0001 although positive lymph node presence perineural invasion presence lymphovascular invasion lvi 7th ajcc uicc tumor node metastasis tnm stage involvement resection margin significant prognostic factors univariate analysis multivariate analysis identified tnm stage lvi independent prognostic factors conclusion pd greater likelihood curative resection r1 resection might positive impact tnm stage lvi independent prognostic factors pubmed","probabilities":0.9799733,"Title":"Prognostic factors in patients with middle and distal bile duct cancers","Abstract":"AIM: To identify the influence of the surgery type and prognostic factors in middle and distal bile duct cancers. METHODS: Between August 1990 and June 2011, data regarding the clinicopathological factors of 194 patients with surgical and pathological confirmation were collected. A total of 133 patients underwent resections (R0, R1, R2; n = 102, 24, 7), whereas 61 patients underwent nonresectional surgery. Either pancreaticoduodenectomy (PD) or bile duct resection (BDR) was selected according to the sites of tumors and co-morbidities of the patients after confirming resection margin by the frozen histology in all cases. Univariate and multivariate analyses of clinicopathologic factors were performed, utilizing the Kaplan-Meyer method and Cox hazard regression analysis. RESULTS: The overall 5-year survival rate for the 133 patients who underwent resection (R0, R1, and R2) was 41.2%, whereas no patients survived longer than 3 years among the 61 patient who underwent nonresectional surgeries. The 5-year survival rate of the patients who underwent a PD (n = 90) was higher than the rate of those who underwent BDR (n = 43), although the difference was not statistically significant (46.6% vs 30.0% P = 0.105). However, PD had a higher rate of R0 resection than BDR (90.0% vs 48.8%, P < 0.0001). If R0 resection was achieved, PD and BDR showed similar survival rates (49.4% vs 46.5% P = 0.762). The 5-year survival rates of R0 and R1 resections were not significantly different (49.0% vs 21.0% P = 0.132), but R2 resections had lower survival (0%, P = 0.0001). Although positive lymph node, presence of perineural invasion, presence of lymphovascular invasion (LVI), 7th AJCC-UICC tumor node metastasis (TNM) stage, and involvement of resection margin were significant prognostic factors in univariate analysis, multivariate analysis identified only TNM stage and LVI as independent prognostic factors. CONCLUSION: PD had a greater likelihood of curative resection and R1 resection might have some positive impact. The TNM stage and LVI were independent prognostic factors.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors in patients with middle and distal bile duct cancers AIM: To identify the influence of the surgery type and prognostic factors in middle and distal bile duct cancers. METHODS: Between August 1990 and June 2011, data regarding the clinicopathological factors of 194 patients with surgical and pathological confirmation were collected. A total of 133 patients underwent resections (R0, R1, R2; n = 102, 24, 7), whereas 61 patients underwent nonresectional surgery. Either pancreaticoduodenectomy (PD) or bile duct resection (BDR) was selected according to the sites of tumors and co-morbidities of the patients after confirming resection margin by the frozen histology in all cases. Univariate and multivariate analyses of clinicopathologic factors were performed, utilizing the Kaplan-Meyer method and Cox hazard regression analysis. RESULTS: The overall 5-year survival rate for the 133 patients who underwent resection (R0, R1, and R2) was 41.2%, whereas no patients survived longer than 3 years among the 61 patient who underwent nonresectional surgeries. The 5-year survival rate of the patients who underwent a PD (n = 90) was higher than the rate of those who underwent BDR (n = 43), although the difference was not statistically significant (46.6% vs 30.0% P = 0.105). However, PD had a higher rate of R0 resection than BDR (90.0% vs 48.8%, P < 0.0001). If R0 resection was achieved, PD and BDR showed similar survival rates (49.4% vs 46.5% P = 0.762). The 5-year survival rates of R0 and R1 resections were not significantly different (49.0% vs 21.0% P = 0.132), but R2 resections had lower survival (0%, P = 0.0001). Although positive lymph node, presence of perineural invasion, presence of lymphovascular invasion (LVI), 7th AJCC-UICC tumor node metastasis (TNM) stage, and involvement of resection margin were significant prognostic factors in univariate analysis, multivariate analysis identified only TNM stage and LVI as independent prognostic factors. CONCLUSION: PD had a greater likelihood of curative resection and R1 resection might have some positive impact. The TNM stage and LVI were independent prognostic factors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"utility fdg pet based volumetric metabolic parameters vmp predicting overall survival patients stage iii iv primary gall bladder carcinoma pgbc objectives aim study evaluate utility vmp derived 18f fdg pet ct predicting overall survival patients diagnosed stage iii iv pgbc methods fdg pet studies 31 patients diagnosed stage iii iv pgbc retrospectively analyzed fdg pet ct acquired 45 min injection 370 440 mbq 18f fdg pet images analyzed vmp including maximal standardized uptake value suvmax metabolic tumor volume mtv total lesion glycolysis tlg using pet vcar software semi automated isoactivity contour voi generated utilizing gradient threshold segmentation algorithm around metabolically active pathological lesions obtain mtv suvmean tlg overall survival estimated duration pet ct imaging death patient roc curves cox hazard regression model used statistical analysis results total 31 patients 24 females 7 males age range 38 75 yrs mean 54 61 yrs 26 patients died disease follow mean duration 6 2 months range 1 16 months median duration overall survival 5 months among non survivors median follow 5 survivors 10 months range 10 16 mtv tlg exhibited greater accuracy suvmax roc analysis auc 0 769 0 762 0 638 respectively prediction event however significant statistical association time death suvmax kaplan meier curves drawn utilizing cutoffs 82 cm3 mtv 270 g ml x cm3 tlg derived roc auc data univariate analysis mtv tlg significant effect overall survival negative regression coefficient 2 33 1 99 respectively conclusions study mtv tlg showed significant prognostic significance overall survival advanced stage disease pgbc thus vmp may impact decision therapeutic intervention role stratifying patients future randomized trials google scholar","probabilities":0.9799733,"Title":"Utility Of Fdg Pet Based Volumetric Metabolic Parameters (Vmp) In Predicting Overall Survival Of Patients With Stage Iii/Iv Primary Gall Bladder Carcinoma (Pgbc)","Abstract":"Objectives Aim of this study was to evaluate the utility of VMP derived from 18F-FDG PET/CT in predicting the overall survival of patients diagnosed with stage III / IV PGBC \nMethods FDG PET studies of 31 patients diagnosed with Stage III/ IV PGBC were retrospectively analyzed. FDG PET/CT was acquired 45 min after the injection of 370 - 440 MBq of 18F FDG. PET images were analyzed for VMP including maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) using PET VCAR software. Semi-automated isoactivity contour VOI’s were generated utilizing the gradient threshold segmentation algorithm around all the metabolically active pathological lesions to obtain MTV, SUVmean and TLG. Overall survival was estimated as duration from the PET/CT imaging to death of the patient. ROC curves and Cox Hazard Regression Model were used for statistical analysis. \nResults Of the total 31 patients (24 Females, 7 Males; Age range 38-75 yrs; mean 54.61 yrs), 26 patients died of the disease on follow up (mean duration 6.2 months, range 1-16 months). Median duration of overall survival was 5 months among the non survivors. The median follow up of the 5 survivors was 10 months (range 10-16). MTV and TLG exhibited greater accuracy than SUVmax on ROC analysis (AUC 0.769, 0.762 and 0.638 respectively) for prediction of event.However, there was no significant statistical association between time to death and SUVmax. Kaplan Meier curves were drawn utilizing these cutoffs of 82 cm3 for MTV and 270 g/ml x cm3 for TLG (derived from the ROC AUC data).On univariate analysis,MTV and TLG had significant effect on overall survival with a negative regression coefficient of 2.33 and 1.99 respectively. \nConclusions In our study, MTV and TLG showed significant prognostic significance on overall survival of advanced stage disease of PGBC. Thus these VMP may have impact on decision for therapeutic intervention and role in stratifying patients for future randomized trials.","Source":"Google Scholar","category":"HUMAN","training_data":"Utility Of Fdg Pet Based Volumetric Metabolic Parameters (Vmp) In Predicting Overall Survival Of Patients With Stage Iii/Iv Primary Gall Bladder Carcinoma (Pgbc) Objectives Aim of this study was to evaluate the utility of VMP derived from 18F-FDG PET/CT in predicting the overall survival of patients diagnosed with stage III / IV PGBC \nMethods FDG PET studies of 31 patients diagnosed with Stage III/ IV PGBC were retrospectively analyzed. FDG PET/CT was acquired 45 min after the injection of 370 - 440 MBq of 18F FDG. PET images were analyzed for VMP including maximal standardized uptake value (SUVmax), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) using PET VCAR software. Semi-automated isoactivity contour VOI’s were generated utilizing the gradient threshold segmentation algorithm around all the metabolically active pathological lesions to obtain MTV, SUVmean and TLG. Overall survival was estimated as duration from the PET/CT imaging to death of the patient. ROC curves and Cox Hazard Regression Model were used for statistical analysis. \nResults Of the total 31 patients (24 Females, 7 Males; Age range 38-75 yrs; mean 54.61 yrs), 26 patients died of the disease on follow up (mean duration 6.2 months, range 1-16 months). Median duration of overall survival was 5 months among the non survivors. The median follow up of the 5 survivors was 10 months (range 10-16). MTV and TLG exhibited greater accuracy than SUVmax on ROC analysis (AUC 0.769, 0.762 and 0.638 respectively) for prediction of event.However, there was no significant statistical association between time to death and SUVmax. Kaplan Meier curves were drawn utilizing these cutoffs of 82 cm3 for MTV and 270 g/ml x cm3 for TLG (derived from the ROC AUC data).On univariate analysis,MTV and TLG had significant effect on overall survival with a negative regression coefficient of 2.33 and 1.99 respectively. \nConclusions In our study, MTV and TLG showed significant prognostic significance on overall survival of advanced stage disease of PGBC. Thus these VMP may have impact on decision for therapeutic intervention and role in stratifying patients for future randomized trials. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"gemcitabine plus cisplatin versus capecitabine plus cisplatin first line chemotherapy advanced biliary tract cancer retrospective cohort study background aim gemcitabine plus cisplatin gp standard chemotherapy option patients advanced biliary tract cancer btc compared efficacy safety capecitabine plus cisplatin xp versus gp advanced btc methods records patients treated gp xp chemotherapy unresectable metastatic recurrent btc national cancer center december 2001 august 2012 reviewed retrospectively patients histologically confirmed intrahepatic cholangiocarcinoma gallbladder cancer extrahepatic cholangiocarcinoma enrolled results 344 patients enrolled 127 received gp 217 received xp median follow time 8 9 months median time progression longer gp group xp group 5 6 vs 4 7 months difference statistically significant p 0 081 median overall survival os 8 4 months 95 ci 6 2 10 7 gp group 7 6 months 95 ci 6 8 8 7 xp group p 0 024 statistical significance retained following multivariate analysis hr 0 72 95 ci 0 527 0 987 p 0 004 grade 3 4 toxicities significantly frequent gp group xp group 40 9 vs 24 9 p 0 002 conclusions gp superior xp prolonging os despite increasing rate grade 3 4 adverse events pubmed","probabilities":0.9799733,"Title":"Gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective cohort study","Abstract":"BACKGROUND AND AIM: Gemcitabine plus cisplatin (GP) is a standard chemotherapy option for patients with advanced biliary tract cancer (BTC). We compared the efficacy and safety of capecitabine plus cisplatin (XP) versus GP in advanced BTC. METHODS: The records of all patients treated with GP or XP chemotherapy for unresectable, metastatic, or recurrent BTC at the National Cancer Center between December 2001 and August 2012 were reviewed retrospectively. Patients with histologically confirmed intrahepatic cholangiocarcinoma, gallbladder cancer, or extrahepatic cholangiocarcinoma were enrolled. RESULTS: Of the 344 patients enrolled, 127 received GP and 217 received XP. At a median follow-up time of 8.9 months, the median time to progression was longer in the GP group than in the XP group (5.6 vs. 4.7 months), but the difference was not statistically significant (p = 0.081). The median overall survival (OS) was 8.4 months (95% CI 6.2-10.7) in the GP group and 7.6 months (95% CI 6.8-8.7) in the XP group (p = 0.024), with statistical significance retained following multivariate analysis (HR 0.72; 95% CI 0.527-0.987; p = 0.004). Grade 3/4 toxicities were significantly more frequent in the GP group than in the XP group (40.9 vs. 24.9%, p = 0.002). CONCLUSIONS: GP was superior to XP in prolonging OS, despite increasing the rate of grade 3/4 adverse events.","Source":"PubMed","category":"HUMAN","training_data":"Gemcitabine plus cisplatin versus capecitabine plus cisplatin as first-line chemotherapy for advanced biliary tract cancer: a retrospective cohort study BACKGROUND AND AIM: Gemcitabine plus cisplatin (GP) is a standard chemotherapy option for patients with advanced biliary tract cancer (BTC). We compared the efficacy and safety of capecitabine plus cisplatin (XP) versus GP in advanced BTC. METHODS: The records of all patients treated with GP or XP chemotherapy for unresectable, metastatic, or recurrent BTC at the National Cancer Center between December 2001 and August 2012 were reviewed retrospectively. Patients with histologically confirmed intrahepatic cholangiocarcinoma, gallbladder cancer, or extrahepatic cholangiocarcinoma were enrolled. RESULTS: Of the 344 patients enrolled, 127 received GP and 217 received XP. At a median follow-up time of 8.9 months, the median time to progression was longer in the GP group than in the XP group (5.6 vs. 4.7 months), but the difference was not statistically significant (p = 0.081). The median overall survival (OS) was 8.4 months (95% CI 6.2-10.7) in the GP group and 7.6 months (95% CI 6.8-8.7) in the XP group (p = 0.024), with statistical significance retained following multivariate analysis (HR 0.72; 95% CI 0.527-0.987; p = 0.004). Grade 3/4 toxicities were significantly more frequent in the GP group than in the XP group (40.9 vs. 24.9%, p = 0.002). CONCLUSIONS: GP was superior to XP in prolonging OS, despite increasing the rate of grade 3/4 adverse events. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intracellular localization mesothelin predicts patient prognosis extrahepatic bile duct cancer mesothelin expressed various types malignant tumors recently reported expression mesothelin related unfavorable patient outcome pancreatic ductal adenocarcinoma gastric adenocarcinoma study examined clinicopathological significance mesothelin expression extrahepatic bile duct cancer ehbdca especially terms association staining pattern tissue samples 61 ehbdca 16 hilar cholangiocarcinoma 17 upper bile duct adenocarci noma 20 middle bile duct adenocarcinoma 8 distal bile duct adenocarcinoma immunohistochemically examined expression levels mesothelin tumor cells classified localization mesothelin luminal membrane cytoplasm addition high low according staining intensity proportion conventional analysis high level expression mesothelin 47 5 statistically correlated liver metastasis p 0 013 poorer patient outcome p 0 022 luminal membrane positive mesothelin 52 5 significantly correlated liver metastasis p 0 006 peritoneal metastasis p 0 024 unfavorable patient outcome p 0 017 moreover found cytoplasmic expression isolated luminal membrane negative mesothelin represented best patient prognosis throughout study describe expression pattern level mesothelin e luminal membrane cytoplasm high low level evidently indicate patient prognosis ehbdca suggesting pivotal role mesothelin cancer promotion depending intracellular localization stn","probabilities":0.7966102,"Title":"Intracellular Localization Of Mesothelin Predicts Patient Prognosis Of Extrahepatic Bile Duct Cancer","Abstract":"Mesothelin is expressed in various types of malignant tumors, and we recently reported that the expression of mesothelin was related to unfavorable patient outcome in pancreatic ductal adenocarcinoma and gastric adenocarcinoma. In this study, we examined the clinicopathological significance of mesothelin expression in extrahepatic bile duct cancer (EHBDCA), especially in terms of its association with the staining pattern. Tissue samples from 61 EHBDCA (16 hilar cholangiocarcinoma, 17 upper bile duct adenocarci-noma, 20 middle bile duct adenocarcinoma and 8 distal bile duct adenocarcinoma) were immunohistochemically examined. The expression levels of mesothelin in tumor cells was classified into the localization of mesothelin in luminal membrane and/or cytoplasm, in addition to high and low according to the staining intensity and proportion as a conventional analysis. 'High-level expression' of mesothelin (47.5%) was statistically correlated with liver metastasis (P=0.013) and poorer patient outcome (P=0.022), while 'luminal membrane positive' of mesothelin (52.5%) was more significantly correlated with liver metastasis (P=0.006), peritoneal metastasis (P=0.024) and unfavorable patient outcome (P=0.017). Moreover, we found that 'cytoplasmic expression' isolated from 'luminal membrane negative' of mesothelin represented the best patient prognosis throughout this study. We describe the expression pattern level of mesothelin, i.e., in luminal membrane or cytoplasm both high and low level, evidently indicate the patient prognosis of EHBDCA, suggesting the pivotal role of mesothelin in cancer promotion depending on its intracellular localization.","Source":"STN","category":"ANIMAL","training_data":"Intracellular Localization Of Mesothelin Predicts Patient Prognosis Of Extrahepatic Bile Duct Cancer Mesothelin is expressed in various types of malignant tumors, and we recently reported that the expression of mesothelin was related to unfavorable patient outcome in pancreatic ductal adenocarcinoma and gastric adenocarcinoma. In this study, we examined the clinicopathological significance of mesothelin expression in extrahepatic bile duct cancer (EHBDCA), especially in terms of its association with the staining pattern. Tissue samples from 61 EHBDCA (16 hilar cholangiocarcinoma, 17 upper bile duct adenocarci-noma, 20 middle bile duct adenocarcinoma and 8 distal bile duct adenocarcinoma) were immunohistochemically examined. The expression levels of mesothelin in tumor cells was classified into the localization of mesothelin in luminal membrane and/or cytoplasm, in addition to high and low according to the staining intensity and proportion as a conventional analysis. 'High-level expression' of mesothelin (47.5%) was statistically correlated with liver metastasis (P=0.013) and poorer patient outcome (P=0.022), while 'luminal membrane positive' of mesothelin (52.5%) was more significantly correlated with liver metastasis (P=0.006), peritoneal metastasis (P=0.024) and unfavorable patient outcome (P=0.017). Moreover, we found that 'cytoplasmic expression' isolated from 'luminal membrane negative' of mesothelin represented the best patient prognosis throughout this study. We describe the expression pattern level of mesothelin, i.e., in luminal membrane or cytoplasm both high and low level, evidently indicate the patient prognosis of EHBDCA, suggesting the pivotal role of mesothelin in cancer promotion depending on its intracellular localization. STN","prediction_labels":"HUMAN"},{"cleaned":"analysis relationships clinicopathologic factors survival gallbladder cancer following surgical resection curative intent background study elucidated relationships various clinicopathologic factors outcome patients gallbladder cancer gbc treated surgical resection curative intent methods january 2003 january 2011 76 patients gbc underwent surgical resection curative intent department conducted retrospective analysis clinicopathologic data fourteen clinicopathological variables selected univariate multivariate analysis evaluate influence outcome results actuarial 1 3 5 year survival rates 76 resected cases 56 6 32 7 23 8 respectively univariate analysis revealed curative resection p 0 001 lymph node metastasis p 0 001 ajcc stage p 0 030 tumor location p 0 008 histologic differentiation p 0 028 intraoperative blood loss p 0 011 preoperative jaundice p 0 012 significant risk factors survival multivariate analysis revealed noncurative resection tumor location gallbladder neck significant risk factors poor outcome among jaundiced patients discovered gallbladder carcinoma tumor thrombus common bile duct cbd rare relatively special clinical manifestation characteristic radiography manifestation prognosis gallbladder carcinoma tumor thrombus cbd surgical procedure apparently better gallbladder carcinoma invasion hilar tissues conclusions curative surgical resection remains effective approach treatment gbc series confirm jaundice poor prognostic factor however presence jaundice preclude resection especially highly selected patients r0 resection achievable gallbladder carcinoma tumor thrombus cbd special clinical characteristics need awared radiologists clinicians pubmed","probabilities":0.88235295,"Title":"Analysis of the relationships between clinicopathologic factors and survival in gallbladder cancer following surgical resection with curative intent","Abstract":"BACKGROUND: This study elucidated the relationships between various clinicopathologic factors and the outcome of patients with gallbladder cancer (GBC) treated by surgical resection with curative intent. METHODS: Between January 2003 and January 2011, 76 patients with GBC underwent surgical resection with curative intent at our department. We then conducted a retrospective analysis of clinicopathologic data. Fourteen clinicopathological variables were selected for univariate and multivariate analysis to evaluate their influence on the outcome. RESULTS: The actuarial 1-, 3-, and 5-year survival rates in the 76 resected cases were 56.6%, 32.7%, and 23.8%, respectively. The univariate analysis revealed that curative resection (P<0.001), lymph node metastasis (P<0.001), AJCC stage (P = 0.030), tumor location (P = 0.008), histologic differentiation (P = 0.028), intraoperative blood loss (P = 0.011), and preoperative jaundice (P = 0.012) were significant risk factors for survival. Multivariate analysis revealed that noncurative resection and tumor location on gallbladder neck were significant risk factors for poor outcome. Among jaundiced patients, we discovered that gallbladder carcinoma with tumor thrombus in common bile duct (CBD) was very rare but with relatively special clinical manifestation and characteristic radiography manifestation. The prognosis of gallbladder carcinoma with tumor thrombus in CBD after surgical procedure was apparently better than gallbladder carcinoma with invasion of hilar tissues. CONCLUSIONS: Curative surgical resection remains the only effective approach to the treatment of GBC. This series confirm that jaundice is a poor prognostic factor. However, the presence of jaundice does not preclude resection, especially in highly selected patients (when R0 resection is achievable). Gallbladder carcinoma with tumor thrombus in CBD has special clinical characteristics, which need to be awared by radiologists and clinicians.","Source":"PubMed","category":"HUMAN","training_data":"Analysis of the relationships between clinicopathologic factors and survival in gallbladder cancer following surgical resection with curative intent BACKGROUND: This study elucidated the relationships between various clinicopathologic factors and the outcome of patients with gallbladder cancer (GBC) treated by surgical resection with curative intent. METHODS: Between January 2003 and January 2011, 76 patients with GBC underwent surgical resection with curative intent at our department. We then conducted a retrospective analysis of clinicopathologic data. Fourteen clinicopathological variables were selected for univariate and multivariate analysis to evaluate their influence on the outcome. RESULTS: The actuarial 1-, 3-, and 5-year survival rates in the 76 resected cases were 56.6%, 32.7%, and 23.8%, respectively. The univariate analysis revealed that curative resection (P<0.001), lymph node metastasis (P<0.001), AJCC stage (P = 0.030), tumor location (P = 0.008), histologic differentiation (P = 0.028), intraoperative blood loss (P = 0.011), and preoperative jaundice (P = 0.012) were significant risk factors for survival. Multivariate analysis revealed that noncurative resection and tumor location on gallbladder neck were significant risk factors for poor outcome. Among jaundiced patients, we discovered that gallbladder carcinoma with tumor thrombus in common bile duct (CBD) was very rare but with relatively special clinical manifestation and characteristic radiography manifestation. The prognosis of gallbladder carcinoma with tumor thrombus in CBD after surgical procedure was apparently better than gallbladder carcinoma with invasion of hilar tissues. CONCLUSIONS: Curative surgical resection remains the only effective approach to the treatment of GBC. This series confirm that jaundice is a poor prognostic factor. However, the presence of jaundice does not preclude resection, especially in highly selected patients (when R0 resection is achievable). Gallbladder carcinoma with tumor thrombus in CBD has special clinical characteristics, which need to be awared by radiologists and clinicians. PubMed","prediction_labels":"HUMAN"},{"cleaned":"high dose rate intraluminal brachytherapy effective palliation cholangiocarcinoma causing bile duct obstruction nan pubmed","probabilities":0.9799733,"Title":"High-dose rate intraluminal brachytherapy: An effective palliation for cholangiocarcinoma causing bile duct obstruction","Abstract":"NaN","Source":"PubMed","category":"HUMAN","training_data":"High-dose rate intraluminal brachytherapy: An effective palliation for cholangiocarcinoma causing bile duct obstruction nan PubMed","prediction_labels":"HUMAN"},{"cleaned":"risk factors morbidity predictors long term survival hepatopancreatoduodenectomy biliary cancer background aims hepatopancreatoduodenectomy hpd performed achieve radical resection malignant biliary tumors reviewed clinical outcomes evaluate utility hpd terms morbidity mortality methodology retrospective analysis conducted 17 patients underwent hpd august 1991 may 2013 9 bile duct cancer 5 advanced gallbladder 3 pancreatic tumor liver metastasis results morbidity mortality rates 88 3 0 respectively univariate analysis showed body mass index 22 preoperative total bilirubin level 0 8 mg dl significantly associated severe complications one 3 5 year survival rate 73 3 60 0 30 0 14 patients biliary carcinoma univariate analysis showed histological grade g1 significantly associated survival patients without pancreatic invasion portal vein invasion tended survive longer patients types invasion although difference significant conclusions hpd performed mortality provides survival benefit patients biliary carcinoma undergoing curative resection patients grade g1 biliary carcinoma without pancreatic portal vein invasion particular aggressive surgery might offer chance long term survival pubmed","probabilities":0.9799733,"Title":"Risk factors of morbidity and predictors of long-term survival after hepatopancreatoduodenectomy for biliary cancer","Abstract":"BACKGROUND/AIMS: Hepatopancreatoduodenectomy (HPD) is performed to achieve radical resection of malignant biliary tumors. We reviewed clinical outcomes to evaluate the utility of HPD in terms of morbidity and mortality. METHODOLOGY: A retrospective analysis was conducted on 17 patients underwent HPD between August 1991 and May 2013; 9 bile duct cancer, 5 advanced gallbladder and 3 pancreatic tumor with liver metastasis. RESULTS: The morbidity and mortality rates were 88.3% and 0%, respectively. Univariate analysis showed that a body mass index of ≥22 and preoperative total bilirubin level ≥0.8 mg/dl were significantly associated with severe complications. One-, 3- and 5-year survival rate were 73.3%, 60.0% and 30.0%. In 14 patients with biliary carcinoma, univariate analysis showed that a histological grade of G1 was significantly associated with survival. Patients without pancreatic invasion or portal vein invasion tended to survive longer than patients with these types of invasion, although the difference was not significant. CONCLUSIONS: HPD can be performed with no mortality and provides a survival benefit for some patients with biliary carcinoma undergoing curative resection. In patients with grade G1 biliary carcinoma without pancreatic or portal vein invasion in particular, this aggressive surgery might offer a chance of long-term survival.","Source":"PubMed","category":"HUMAN","training_data":"Risk factors of morbidity and predictors of long-term survival after hepatopancreatoduodenectomy for biliary cancer BACKGROUND/AIMS: Hepatopancreatoduodenectomy (HPD) is performed to achieve radical resection of malignant biliary tumors. We reviewed clinical outcomes to evaluate the utility of HPD in terms of morbidity and mortality. METHODOLOGY: A retrospective analysis was conducted on 17 patients underwent HPD between August 1991 and May 2013; 9 bile duct cancer, 5 advanced gallbladder and 3 pancreatic tumor with liver metastasis. RESULTS: The morbidity and mortality rates were 88.3% and 0%, respectively. Univariate analysis showed that a body mass index of ≥22 and preoperative total bilirubin level ≥0.8 mg/dl were significantly associated with severe complications. One-, 3- and 5-year survival rate were 73.3%, 60.0% and 30.0%. In 14 patients with biliary carcinoma, univariate analysis showed that a histological grade of G1 was significantly associated with survival. Patients without pancreatic invasion or portal vein invasion tended to survive longer than patients with these types of invasion, although the difference was not significant. CONCLUSIONS: HPD can be performed with no mortality and provides a survival benefit for some patients with biliary carcinoma undergoing curative resection. In patients with grade G1 biliary carcinoma without pancreatic or portal vein invasion in particular, this aggressive surgery might offer a chance of long-term survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival outcome prognostic factors distal cholangiocarcinoma following surgical resection meta analysis 5 year survival purpose assess available evidence prognostic factors 5 year survival patients distal cholangiocarcinoma dcc following surgical resection methods performed comprehensive search abstracts included databases relevant studies published january 2000 august 2015 risk ratios rrs 95 confidence intervals 95 cis random effects model calculated using revman 5 3 software results total 23 observational studies involving 2063 patients dcc analyzed meta analysis showed postoperative adjuvant chemotherapy confirmed prognostic factor similar 5 year survival rates receiving receiving chemotherapy rr 0 71 95 ci 0 21 2 36 p 0 57 perineural invasion rr 0 51 95 ci 0 40 0 64 p 0 00001 lymph node metastasis rr 0 51 95 ci 0 38 0 70 p 0 0001 positive resection margin status rr 2 11 95 ci 1 36 3 30 p 0 001 well differentiated adenocarcinoma rr 1 77 95 ci 1 39 2 25 p 0 00001 associated shorter survival conclusions perineural invasion lymph node metastasis resection margin status tumor differentiation significant prognostic factors 5 year survival pubmed","probabilities":0.9799733,"Title":"The survival outcome and prognostic factors for distal cholangiocarcinoma following surgical resection: a meta-analysis for the 5-year survival","Abstract":"PURPOSE: To assess the available evidence on the prognostic factors for the 5-year survival for patients with distal cholangiocarcinoma (DCC) following surgical resection. METHODS: We performed a comprehensive search of abstracts included in databases where relevant studies were published between January 2000 and August 2015. Risk ratios (RRs), 95 % confidence intervals (95 % CIs), and random-effects model were calculated using RevMan 5.3 software. RESULTS: A total of 23 observational studies involving 2063 patients with DCC were analyzed. The meta-analysis showed that postoperative adjuvant chemotherapy was not confirmed as a prognostic factor, with similar 5-year survival rates between those receiving and not receiving chemotherapy (RR 0.71; 95 % CI 0.21-2.36; P = 0.57). Perineural invasion (RR 0.51; 95 % CI 0.40-0.64; P < 0.00001), lymph node metastasis (RR 0.51; 95 % CI 0.38-0.70; P < 0.0001), positive resection margin status (RR 2.11; 95 % CI 1.36-3.30; P = 0.001), and not-well-differentiated adenocarcinoma (RR 1.77; 95 % CI 1.39-2.25; P < 0.00001) were associated with shorter survival. CONCLUSIONS: Perineural invasion, lymph node metastasis, resection margin status, and tumor differentiation were the significant prognostic factors for the 5-year survival.","Source":"PubMed","category":"HUMAN","training_data":"The survival outcome and prognostic factors for distal cholangiocarcinoma following surgical resection: a meta-analysis for the 5-year survival PURPOSE: To assess the available evidence on the prognostic factors for the 5-year survival for patients with distal cholangiocarcinoma (DCC) following surgical resection. METHODS: We performed a comprehensive search of abstracts included in databases where relevant studies were published between January 2000 and August 2015. Risk ratios (RRs), 95 % confidence intervals (95 % CIs), and random-effects model were calculated using RevMan 5.3 software. RESULTS: A total of 23 observational studies involving 2063 patients with DCC were analyzed. The meta-analysis showed that postoperative adjuvant chemotherapy was not confirmed as a prognostic factor, with similar 5-year survival rates between those receiving and not receiving chemotherapy (RR 0.71; 95 % CI 0.21-2.36; P = 0.57). Perineural invasion (RR 0.51; 95 % CI 0.40-0.64; P < 0.00001), lymph node metastasis (RR 0.51; 95 % CI 0.38-0.70; P < 0.0001), positive resection margin status (RR 2.11; 95 % CI 1.36-3.30; P = 0.001), and not-well-differentiated adenocarcinoma (RR 1.77; 95 % CI 1.39-2.25; P < 0.00001) were associated with shorter survival. CONCLUSIONS: Perineural invasion, lymph node metastasis, resection margin status, and tumor differentiation were the significant prognostic factors for the 5-year survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intraductal radiofrequency ablation followed locoregional tumor treatments treating occluded biliary stents non resectable malignant biliary obstruction single institution experience objectives determine safety feasibility intraductal radiofrequency ablation rfa followed locoregional tumor treatments patients non resectable malignant biliary obstruction stent re occlusion methods fourteen patients malignant biliary obstruction blocked metal stents studied retrospectively intraductal rfa followed locoregional tumor treatments monitored clinically radiologically practicality safety postoperative complications jaundice remission stent patency survival time analyzed results combination treatment successful patients severe complications rfa local treatments patients stent patency restored decline serum bilirubin three patients recurrent jaundice 195 237 357 days two patients underwent repeat intraductal rfa one required internal external biliary drain average stent patency time 234 days range 187 544 days median follow 384 days range 187 544 days six patients alive eight died mortality 30 days 3 6 12 18 month survival rates 100 100 64 3 42 9 respectively conclusion intraductal rfa followed locoregional tumor treatments occluded metal stents safe practically feasible potential increase stent patency survival times pubmed","probabilities":0.9799733,"Title":"Intraductal Radiofrequency Ablation Followed by Locoregional Tumor Treatments for Treating Occluded Biliary Stents in Non-Resectable Malignant Biliary Obstruction: A Single-Institution Experience","Abstract":"OBJECTIVES: To determine the safety and feasibility of intraductal radiofrequency ablation (RFA) followed by locoregional tumor treatments in patients with non-resectable malignant biliary obstruction and stent re-occlusion. METHODS: Fourteen patients with malignant biliary obstruction and blocked metal stents were studied retrospectively. All had intraductal RFA followed by locoregional tumor treatments and were monitored clinically and radiologically. The practicality, safety, postoperative complications, jaundice remission, stent patency and survival time were analyzed. RESULTS: Combination treatment was successful for all patients. There were no severe complications during RFA or local treatments. All patients had stent patency restored, with a decline in serum bilirubin. Three patients had recurrent jaundice by 195, 237 and 357 days; two patients underwent repeat intraductal RFA; and one required an internal-external biliary drain. The average stent patency time was 234 days (range 187-544 days). With a median follow-up of 384 days (range 187-544 days), six patients were alive, while eight had died. There was no mortality at 30 days. The 3, 6, 12 and 18 month survival rates were 100%, 100%, 64.3% and 42.9%, respectively. CONCLUSION: Intraductal RFA followed by locoregional tumor treatments for occluded metal stents is safe and practically feasible and potential increase stent patency and survival times.","Source":"PubMed","category":"HUMAN","training_data":"Intraductal Radiofrequency Ablation Followed by Locoregional Tumor Treatments for Treating Occluded Biliary Stents in Non-Resectable Malignant Biliary Obstruction: A Single-Institution Experience OBJECTIVES: To determine the safety and feasibility of intraductal radiofrequency ablation (RFA) followed by locoregional tumor treatments in patients with non-resectable malignant biliary obstruction and stent re-occlusion. METHODS: Fourteen patients with malignant biliary obstruction and blocked metal stents were studied retrospectively. All had intraductal RFA followed by locoregional tumor treatments and were monitored clinically and radiologically. The practicality, safety, postoperative complications, jaundice remission, stent patency and survival time were analyzed. RESULTS: Combination treatment was successful for all patients. There were no severe complications during RFA or local treatments. All patients had stent patency restored, with a decline in serum bilirubin. Three patients had recurrent jaundice by 195, 237 and 357 days; two patients underwent repeat intraductal RFA; and one required an internal-external biliary drain. The average stent patency time was 234 days (range 187-544 days). With a median follow-up of 384 days (range 187-544 days), six patients were alive, while eight had died. There was no mortality at 30 days. The 3, 6, 12 and 18 month survival rates were 100%, 100%, 64.3% and 42.9%, respectively. CONCLUSION: Intraductal RFA followed by locoregional tumor treatments for occluded metal stents is safe and practically feasible and potential increase stent patency and survival times. PubMed","prediction_labels":"HUMAN"},{"cleaned":"toxicity carcinogenicity furan human diet furan formed commercial domestic thermal treatment food initial surveys furan concentrations heat treated foods published european us authorities revealed presence relatively high furan levels coffee sauces soups importantly furan consistently found commercial ready eat baby foods furan induces hepatocellular tumors rats mice bile duct tumors rats high incidence epidemiological studies available assumed cis 2 butene 1 4 dial reactive metabolite furan causative agent leading toxicity carcinogenicity based data furan classified possible human carcinogen initial exposure estimates revealed relatively small margin 2 000 human exposure furan doses induce liver tumors experimental animals may give rise concern review currently available toxicological mechanistic data furan summarized discussed regard applicability assessing risk furan human diet stn","probabilities":1.0,"Title":"Toxicity And Carcinogenicity Of Furan In Human Diet","Abstract":"Furan is formed during commercial or domestic thermal treatment of food. The initial surveys of furan concentrations in heat-treated foods, published by European and US authorities, revealed the presence of relatively high furan levels in coffee, sauces, and soups. Importantly, furan is consistently found in commercial ready-to-eat baby foods. Furan induces hepatocellular tumors in rats and mice and bile duct tumors in rats with a high incidence. Epidemiological studies are not available. It is assumed that cis-2-butene-1,4-dial, the reactive metabolite of furan, is the causative agent leading to toxicity and carcinogenicity. Based on this data, furan is classified as a possible human carcinogen. The initial exposure estimates revealed a relatively small margin (~2,000) between human exposure and those furan doses, which induce liver tumors in experimental animals. As this may give rise for concern, in this review, the currently available toxicological and mechanistic data of furan are summarized and discussed with regard to its applicability in assessing the risk of furan in human diet.","Source":"STN","category":"ANIMAL","training_data":"Toxicity And Carcinogenicity Of Furan In Human Diet Furan is formed during commercial or domestic thermal treatment of food. The initial surveys of furan concentrations in heat-treated foods, published by European and US authorities, revealed the presence of relatively high furan levels in coffee, sauces, and soups. Importantly, furan is consistently found in commercial ready-to-eat baby foods. Furan induces hepatocellular tumors in rats and mice and bile duct tumors in rats with a high incidence. Epidemiological studies are not available. It is assumed that cis-2-butene-1,4-dial, the reactive metabolite of furan, is the causative agent leading to toxicity and carcinogenicity. Based on this data, furan is classified as a possible human carcinogen. The initial exposure estimates revealed a relatively small margin (~2,000) between human exposure and those furan doses, which induce liver tumors in experimental animals. As this may give rise for concern, in this review, the currently available toxicological and mechanistic data of furan are summarized and discussed with regard to its applicability in assessing the risk of furan in human diet. STN","prediction_labels":"ANIMAL"},{"cleaned":"toxicology carcinogenesis studies 23 44 5 pentachlorobiphenyl pcb 118 cas 31508 00 6 female harlan sprague dawley rats gavage studies dioxin toxic equivalency factor evaluation overview polyhalogenated aromatic hydrocarbons 2 3 7 8 tetrachlorodibenzo p dioxin tcdd ability bind activate ligand activated transcription factor aryl hydrocarbon receptor ahr structurally related compounds bind ahr exhibit biological actions similar tcdd commonly referred dioxin like compounds dlcs ambient human exposure dlcs occurs ingestion foods containing residues dlcs bioconcentrate food chain due lipophilicity persistence internalized accumulate adipose tissue resulting chronic lifetime human exposure since human exposure dlcs always occurs complex mixture toxic equivalency factor tef methodology developed mathematical tool assess health risk posed complex mixtures compounds tef methodology relative potency scheme ranks dioxin like activity compound relative tcdd potent congener allows estimation potential dioxin like activity mixture chemicals based common mechanism action involving initial binding dlcs ahr toxic equivalency dlcs nominated evaluation widespread human exposure dlcs lack data adequacy tef methodology predicting relative potency cancer risk address national toxicology program conducted series 2 year bioassays female harlan sprague dawley rats evaluate chronic toxicity carcinogenicity dlcs structurally related polychlorinated biphenyls pcbs mixtures compounds polychlorinated biphenyls pcbs mixtures including 2 3 4 4 5 pentachlorobiphenyl pcb 118 produced commercially 1977 electric industry dielectric insulating fluids transformers capacitors manufacture use chemicals stopped increased pcb residues environment continue released environment use disposal products containing pcbs products manufacture certain organic chemicals combustion waste materials atmospheric recycling pcb 118 study conducted part dioxin tef evaluation included multiple 2 year rat bioassays evaluate relative chronic toxicity carcinogenicity dlcs structurally related pcbs mixtures compounds female harlan sprague dawley rats administered pcb 118 least 99 pure corn oil acetone 99 1 gavage 14 31 53 weeks 2 years 2 year study groups 80 female rats administered 100 220 460 1 000 4 600 g pcb 118 kg body weight corn oil acetone 99 1 gavage 5 days per week 105 weeks group 80 vehicle control female rats received corn oil acetone vehicle alone groups 30 female rats received 10 30 g kg 53 weeks 10 rats per group evaluated 14 31 53 weeks stop exposure group 50 female rats administered 4 600 g kg pcb 118 corn oil acetone 99 1 gavage 30 weeks vehicle remainder study survival dosed groups rats similar vehicle control group mean body weights 1 000 g kg rats 7 less vehicle controls week 36 4 600 g kg core study stop exposure groups 7 less vehicle controls week 7 following cessation treatment body weight gain stop exposure group similar vehicle control group general exposure pcb 118 lead dose dependent decreases concentrations serum total thyroxine t4 free t4 dosed groups effects triiodothyronine thyroid stimulating hormone levels dosed groups evaluated 14 31 53 week interim evaluations increases hepatic cell proliferation 4 600 g kg group 14 31 53 weeks administration pcb 118 led dose dependent increases cyp1a1 associated 7 ethoxyresorufin o deethylase cyp1a2 associated acetanilide4 hydroxylase cyp2b associated pentoxyresorufin o deethylase activities 14 31 53 week interim evaluations analysis pcb 118 concentrations dosed groups showed dose duration dosing dependent increases fat liver lung blood highest concentrations seen fat 2 years lower concentrations observed liver lung blood 53 week interim evaluation three 4 600 g kg rats liver cholangiocarcinoma one hepatocellular adenoma 2 years significant treatment related increases incidences cholangiocarcinoma hepatocellular adenoma four incidences hepatocholangioma occurred 4 600 g kg core study group 2 years significant dose related increase hepatic toxicity observed characterized increased incidences numerous lesions including hepatocyte hypertrophy inflammation oval cell hyperplasia pigmentation multinucleated hepatocyte eosinophilic mixed cell foci diffuse fatty change toxic hepatopathy nodular hyperplasia necrosis bile duct hyperplasia cyst cholangiofibrosis incidences lesions often decreased 4 600 g kg stop exposure group compared 4 600 g kg core study group lung 2 years significantly increased incidence cystic keratinizing epithelioma occurred 4 600 g kg core study group compared vehicle control group incidence incidences bronchiolar metaplasia alveolar epithelium significantly increased groups administered 460 g kg greater incidence squamous metaplasia significantly increased 4 600 g kg core study group incidence carcinoma uterus 4 600 g kg stop exposure group significantly greater vehicle control 4 600 g kg core study groups 2 years marginal increase squamous cell carcinoma occurred 220 g kg group 2 years marginally increased incidences exocrine pancreatic adenoma carcinoma 460 1 000 4 600 g kg core study groups numerous nonneoplastic effects seen organs including adrenal cortical atrophy cytoplasmic vacuolization pancreatic acinar cell cytoplasmic vacuolization arterial chronic active inflammation follicular cell hypertrophy thyroid gland inflammation respiratory epithelial hyperplasia nose kidney pigmentation google scholar","probabilities":0.9467213,"Title":"Toxicology And Carcinogenesis Studies Of 23'44'5-Pentachlorobiphenyl (Pcb 118) (Cas No 31508-00-6) In Female Harlan Sprague-Dawley Rats (Gavage Studies)","Abstract":"Dioxin Toxic Equivalency Factor Evaluation Overview- Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as \"dioxin-like compounds\"(DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized they accumulate in adipose tissue resulting in chronic lifetime human exposure. Since human exposure to DLCs always occurs as a complex mixture, the toxic equivalency factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally related polychlorinated biphenyls (PCBs) and mixtures of these compounds. Polychlorinated biphenyls (PCBs) and their mixtures including 2,3',4,4',5-pentachlorobiphenyl (PCB 118) were produced commercially before 1977 for the electric industry as dielectric insulating fluids for transformers and capacitors. Manufacture and use of these chemicals were stopped because of increased PCB residues in the environment, but they continue to be released into the environment through the use and disposal of products containing PCBs, as by-products during the manufacture of certain organic chemicals, during combustion of some waste materials, and during atmospheric recycling. This PCB 118 study was conducted as part of the dioxin TEF evaluation that included multiple 2-year rat bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLCs, structurally related PCBs, and mixtures of these compounds. Female Harlan Sprague-Dawley rats were administered PCB 118 (at least 99% pure) in corn oil:acetone (99:1) by gavage for 14, 31, or 53 weeks or 2 years. 2-YEAR STUDY: Groups of 80 female rats were administered 100, 220, 460, 1,000, or 4,600 g PCB 118/kg body weight in corn oil:acetone (99:1) by gavage, 5 days per week, for up to 105 weeks; a group of 80 vehicle control female rats received the corn oil/acetone vehicle alone. Groups of 30 female rats received 10 or 30 g/kg for up to 53 weeks only. Up to 10 rats per group were evaluated at 14, 31, or 53 weeks. A stop-exposure group of 50 female rats was administered 4,600 g/kg PCB 118 in corn oil:acetone (99:1) by gavage for 30 weeks then the vehicle for the remainder of the study. Survival of all dosed groups of rats was similar to that of the vehicle control group. Mean body weights of 1,000 g/kg rats were 7% less than those of the vehicle controls after week 36, and those of the 4,600 g/kg core study and stop-exposure groups were 7% less than those of the vehicle controls after week 7. Following cessation of treatment, the body weight gain in the stop-exposure group was similar to that of the vehicle control group. In general, exposure to PCB 118 lead to dose-dependent decreases in the concentrations of serum total thyroxine (T4) and free T4 in all dosed groups. There were no effects on triiodothyronine or thyroid stimulating hormone levels in any dosed groups evaluated at the 14-, 31-, and 53-week interim evaluations. There were increases in hepatic cell proliferation in the 4,600 g/kg group at 14, 31, and 53 weeks. Administration of PCB 118 led to dose-dependent increases in CYP1A1-associated 7-ethoxyresorufin-O-deethylase, CYP1A2-associated acetanilide4-hydroxylase, and CYP2B-associated pentoxyresorufin-O-deethylase activities at the 14-, 31-, and 53-week interim evaluations. Analysis of PCB 118 concentrations in dosed groups showed dose- and duration of dosing-dependent increases in fat, liver, lung, and blood. The highest concentrations were seen in fat at 2 years with lower concentrations observed in the liver, lung, and blood. At the 53-week interim evaluation, three 4,600 g/kg rats had liver cholangiocarcinoma and one had hepatocellular adenoma. At 2 years, there were significant treatment-related increases in the incidences of cholangiocarcinoma and hepatocellular adenoma. Four incidences of hepatocholangioma occurred in the 4,600 g/kg core study group. At 2 years, a significant dose-related increase in hepatic toxicity was observed and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, inflammation, oval cell hyperplasia, pigmentation, multinucleated hepatocyte, eosinophilic and mixed cell foci, diffuse fatty change, toxic hepatopathy, nodular hyperplasia, necrosis, bile duct hyperplasia and cyst, and cholangiofibrosis. The incidences of these lesions were often decreased in the 4,600 g/kg stop-exposure group compared to the 4,600 g/kg core study group. In the lung at 2 years, a significantly increased incidence of cystic keratinizing epithelioma occurred in the 4,600 g/kg core study group compared to the vehicle control group incidence. Incidences of bronchiolar metaplasia of the alveolar epithelium were significantly increased in the groups administered 460 g/kg or greater, and the incidence of squamous metaplasia was significantly increased in the 4,600 g/kg core study group. The incidence of carcinoma of the uterus in the 4,600 g/kg stop-exposure group was significantly greater than those in the vehicle control and 4,600 g/kg core study groups at 2 years. A marginal increase in squamous cell carcinoma occurred in the 220 g/kg group. At 2 years, there were marginally increased incidences of exocrine pancreatic adenoma or carcinoma in the 460, 1,000, and 4,600 g/kg core study groups. Numerous nonneoplastic effects were seen in other organs including: adrenal cortical atrophy and cytoplasmic vacuolization, pancreatic acinar cell cytoplasmic vacuolization and arterial chronic active inflammation, follicular cell hypertrophy of the thyroid gland, inflammation and respiratory epithelial hyperplasia of the nose, and kidney pigmentation.","Source":"Google Scholar","category":"ANIMAL","training_data":"Toxicology And Carcinogenesis Studies Of 23'44'5-Pentachlorobiphenyl (Pcb 118) (Cas No 31508-00-6) In Female Harlan Sprague-Dawley Rats (Gavage Studies) Dioxin Toxic Equivalency Factor Evaluation Overview- Polyhalogenated aromatic hydrocarbons such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have the ability to bind to and activate the ligand-activated transcription factor, the aryl hydrocarbon receptor (AhR). Structurally related compounds that bind to the AhR and exhibit biological actions similar to TCDD are commonly referred to as \"dioxin-like compounds\"(DLCs). Ambient human exposure to DLCs occurs through the ingestion of foods containing residues of DLCs that bioconcentrate through the food chain. Due to their lipophilicity and persistence, once internalized they accumulate in adipose tissue resulting in chronic lifetime human exposure. Since human exposure to DLCs always occurs as a complex mixture, the toxic equivalency factor (TEF) methodology has been developed as a mathematical tool to assess the health risk posed by complex mixtures of these compounds. The TEF methodology is a relative potency scheme that ranks the dioxin-like activity of a compound relative to TCDD, which is the most potent congener. This allows for the estimation of the potential dioxin-like activity of a mixture of chemicals, based on a common mechanism of action involving an initial binding of DLCs to the AhR. The toxic equivalency of DLCs was nominated for evaluation because of the widespread human exposure to DLCs and the lack of data on the adequacy of the TEF methodology for predicting relative potency for cancer risk. To address this, the National Toxicology Program conducted a series of 2-year bioassays in female Harlan Sprague-Dawley rats to evaluate the chronic toxicity and carcinogenicity of DLCs and structurally related polychlorinated biphenyls (PCBs) and mixtures of these compounds. Polychlorinated biphenyls (PCBs) and their mixtures including 2,3',4,4',5-pentachlorobiphenyl (PCB 118) were produced commercially before 1977 for the electric industry as dielectric insulating fluids for transformers and capacitors. Manufacture and use of these chemicals were stopped because of increased PCB residues in the environment, but they continue to be released into the environment through the use and disposal of products containing PCBs, as by-products during the manufacture of certain organic chemicals, during combustion of some waste materials, and during atmospheric recycling. This PCB 118 study was conducted as part of the dioxin TEF evaluation that included multiple 2-year rat bioassays to evaluate the relative chronic toxicity and carcinogenicity of DLCs, structurally related PCBs, and mixtures of these compounds. Female Harlan Sprague-Dawley rats were administered PCB 118 (at least 99% pure) in corn oil:acetone (99:1) by gavage for 14, 31, or 53 weeks or 2 years. 2-YEAR STUDY: Groups of 80 female rats were administered 100, 220, 460, 1,000, or 4,600 g PCB 118/kg body weight in corn oil:acetone (99:1) by gavage, 5 days per week, for up to 105 weeks; a group of 80 vehicle control female rats received the corn oil/acetone vehicle alone. Groups of 30 female rats received 10 or 30 g/kg for up to 53 weeks only. Up to 10 rats per group were evaluated at 14, 31, or 53 weeks. A stop-exposure group of 50 female rats was administered 4,600 g/kg PCB 118 in corn oil:acetone (99:1) by gavage for 30 weeks then the vehicle for the remainder of the study. Survival of all dosed groups of rats was similar to that of the vehicle control group. Mean body weights of 1,000 g/kg rats were 7% less than those of the vehicle controls after week 36, and those of the 4,600 g/kg core study and stop-exposure groups were 7% less than those of the vehicle controls after week 7. Following cessation of treatment, the body weight gain in the stop-exposure group was similar to that of the vehicle control group. In general, exposure to PCB 118 lead to dose-dependent decreases in the concentrations of serum total thyroxine (T4) and free T4 in all dosed groups. There were no effects on triiodothyronine or thyroid stimulating hormone levels in any dosed groups evaluated at the 14-, 31-, and 53-week interim evaluations. There were increases in hepatic cell proliferation in the 4,600 g/kg group at 14, 31, and 53 weeks. Administration of PCB 118 led to dose-dependent increases in CYP1A1-associated 7-ethoxyresorufin-O-deethylase, CYP1A2-associated acetanilide4-hydroxylase, and CYP2B-associated pentoxyresorufin-O-deethylase activities at the 14-, 31-, and 53-week interim evaluations. Analysis of PCB 118 concentrations in dosed groups showed dose- and duration of dosing-dependent increases in fat, liver, lung, and blood. The highest concentrations were seen in fat at 2 years with lower concentrations observed in the liver, lung, and blood. At the 53-week interim evaluation, three 4,600 g/kg rats had liver cholangiocarcinoma and one had hepatocellular adenoma. At 2 years, there were significant treatment-related increases in the incidences of cholangiocarcinoma and hepatocellular adenoma. Four incidences of hepatocholangioma occurred in the 4,600 g/kg core study group. At 2 years, a significant dose-related increase in hepatic toxicity was observed and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, inflammation, oval cell hyperplasia, pigmentation, multinucleated hepatocyte, eosinophilic and mixed cell foci, diffuse fatty change, toxic hepatopathy, nodular hyperplasia, necrosis, bile duct hyperplasia and cyst, and cholangiofibrosis. The incidences of these lesions were often decreased in the 4,600 g/kg stop-exposure group compared to the 4,600 g/kg core study group. In the lung at 2 years, a significantly increased incidence of cystic keratinizing epithelioma occurred in the 4,600 g/kg core study group compared to the vehicle control group incidence. Incidences of bronchiolar metaplasia of the alveolar epithelium were significantly increased in the groups administered 460 g/kg or greater, and the incidence of squamous metaplasia was significantly increased in the 4,600 g/kg core study group. The incidence of carcinoma of the uterus in the 4,600 g/kg stop-exposure group was significantly greater than those in the vehicle control and 4,600 g/kg core study groups at 2 years. A marginal increase in squamous cell carcinoma occurred in the 220 g/kg group. At 2 years, there were marginally increased incidences of exocrine pancreatic adenoma or carcinoma in the 460, 1,000, and 4,600 g/kg core study groups. Numerous nonneoplastic effects were seen in other organs including: adrenal cortical atrophy and cytoplasmic vacuolization, pancreatic acinar cell cytoplasmic vacuolization and arterial chronic active inflammation, follicular cell hypertrophy of the thyroid gland, inflammation and respiratory epithelial hyperplasia of the nose, and kidney pigmentation. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"hepatic arterial infusion polyethylene glycol drug eluting beads primary metastatic liver cancer therapy background aim recently launch new polyethylene glycol peg drug eluting beads lifepearl transarterial chemoembolization innovation peg guarantees compressibility elasticity maximizes beads suspension time applied beads hepatic intra arterial infusion irinotecan doxorubicin therapy primary metastatic liver cancer patients methods treated 20 consecutive patients affected unresectable primary liver cancer plc hepatic metastases refractory chemotherapy using chemoembolization doxorubicin irinotecan pre loaded lifepearls results tumor response rate 80 patients 63 complete 37 partial response observed complications chemoembolization severe general drug related side effects conclusion data suggest chemoembolization lifepearl efficacious safe treatment liver cancer indicated good tolerability quality life high tumor response pubmed","probabilities":0.9799733,"Title":"Hepatic Arterial Infusion of Polyethylene Glycol Drug-eluting Beads for Primary and Metastatic Liver Cancer Therapy","Abstract":"BACKGROUND/AIM: Recently, there has been the launch of the new Polyethylene glycol (PEG) drug-eluting beads (LifePearl®) for transarterial chemoembolization. Their innovation is that PEG guarantees more compressibility, elasticity and maximizes beads' suspension time. We applied these beads for hepatic intra-arterial infusion of irinotecan or doxorubicin for the therapy of primary and metastatic liver cancer. PATIENTS AND METHODS: We treated 20 consecutive patients, affected by unresectable primary liver cancer (PLC) or hepatic metastases (refractory to chemotherapy) using chemoembolization with doxorubicin or irinotecan pre-loaded Lifepearls. RESULTS: Tumor response rate was >80% in most patients with 63% of complete and 37% of partial response. We observed no complications during the chemoembolization and no severe general drug-related side-effects. CONCLUSION: Our data suggest that chemoembolization with LifePearl® is efficacious and safe for the treatment of liver cancer as indicated by good tolerability, quality of life and high tumor response.","Source":"PubMed","category":"HUMAN","training_data":"Hepatic Arterial Infusion of Polyethylene Glycol Drug-eluting Beads for Primary and Metastatic Liver Cancer Therapy BACKGROUND/AIM: Recently, there has been the launch of the new Polyethylene glycol (PEG) drug-eluting beads (LifePearl®) for transarterial chemoembolization. Their innovation is that PEG guarantees more compressibility, elasticity and maximizes beads' suspension time. We applied these beads for hepatic intra-arterial infusion of irinotecan or doxorubicin for the therapy of primary and metastatic liver cancer. PATIENTS AND METHODS: We treated 20 consecutive patients, affected by unresectable primary liver cancer (PLC) or hepatic metastases (refractory to chemotherapy) using chemoembolization with doxorubicin or irinotecan pre-loaded Lifepearls. RESULTS: Tumor response rate was >80% in most patients with 63% of complete and 37% of partial response. We observed no complications during the chemoembolization and no severe general drug-related side-effects. CONCLUSION: Our data suggest that chemoembolization with LifePearl® is efficacious and safe for the treatment of liver cancer as indicated by good tolerability, quality of life and high tumor response. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison 7th 8th editions american joint committee cancer staging systems perihilar cholangiocarcinoma background performances american joint committee cancer staging systems 7th 8th edition compared using cohort patients undergoing surgery perihilar cholangiocarcinoma 2 tertiary referral italian hepatobiliary centers methods american joint committee cancer 7th 8th edition staging systems used classify 214 patients underwent surgery perihilar cholangiocarcinoma performances 2 staging systems compared using concordance index results using american joint committee cancer 7th edition staging system found 5 year overall survival stages ii iva 71 34 34 patients stages iiia iiib ivb survived 5 years comparison american joint committee cancer 8th edition staging system used 5 year overall survival 71 35 stages ii resulting 23 19 22 stages iiia iiib iiic respectively note patients stages iva ivb survived 5 years american joint committee cancer 8th edition staging system slightly better discriminatory ability concordance index 0 624 compared 0 619 american joint committee cancer 7th edition conclusion newly released classification american joint committee cancer 8th edition staging system demonstrated poor moderate ability predict prognosis patients undergoing liver resection perihilar cholangiocarcinoma slightly better previous edition refinements needed improve prognostic ability american joint committee cancer staging system perihilar cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Comparison of the 7th and 8th editions of the American Joint Committee on Cancer Staging Systems for perihilar cholangiocarcinoma","Abstract":"BACKGROUND: The performances of the American Joint Committee on Cancer staging systems of the 7th and 8th edition were compared using a cohort of patients undergoing surgery for perihilar cholangiocarcinoma at 2 tertiary referral Italian hepatobiliary centers. METHODS: The American Joint Committee on Cancer 7th and 8th edition staging systems were used to classify 214 patients who underwent surgery for perihilar cholangiocarcinoma. The performances of the 2 staging systems were compared using the concordance index. RESULTS: Using the American Joint Committee on Cancer 7th edition staging system, we found that the 5-year overall survival for stages I, II, and IVa was 71%, 34%, and 34%, while no patients in stages IIIa, IIIb, and IVb survived 5 years. In comparison, when the American Joint Committee on Cancer 8th edition staging system was used, the 5-year overall survival was 71% and 35% in stages I and II, resulting in 23%, 19%, and 22% in stages IIIa, IIIb, and IIIc, respectively. Of note, no patients in stages IVa and IVb survived 5 years. The American Joint Committee on Cancer 8th edition staging system had a slightly better discriminatory ability with a concordance index of 0.624 compared with 0.619 for the American Joint Committee on Cancer 7th edition. CONCLUSION: The newly released classification American Joint Committee on Cancer 8th edition staging system demonstrated a poor to moderate ability to predict prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma, which was only slightly better than the previous edition. Further refinements are needed to improve the prognostic ability of the American Joint Committee on Cancer staging system for perihilar cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Comparison of the 7th and 8th editions of the American Joint Committee on Cancer Staging Systems for perihilar cholangiocarcinoma BACKGROUND: The performances of the American Joint Committee on Cancer staging systems of the 7th and 8th edition were compared using a cohort of patients undergoing surgery for perihilar cholangiocarcinoma at 2 tertiary referral Italian hepatobiliary centers. METHODS: The American Joint Committee on Cancer 7th and 8th edition staging systems were used to classify 214 patients who underwent surgery for perihilar cholangiocarcinoma. The performances of the 2 staging systems were compared using the concordance index. RESULTS: Using the American Joint Committee on Cancer 7th edition staging system, we found that the 5-year overall survival for stages I, II, and IVa was 71%, 34%, and 34%, while no patients in stages IIIa, IIIb, and IVb survived 5 years. In comparison, when the American Joint Committee on Cancer 8th edition staging system was used, the 5-year overall survival was 71% and 35% in stages I and II, resulting in 23%, 19%, and 22% in stages IIIa, IIIb, and IIIc, respectively. Of note, no patients in stages IVa and IVb survived 5 years. The American Joint Committee on Cancer 8th edition staging system had a slightly better discriminatory ability with a concordance index of 0.624 compared with 0.619 for the American Joint Committee on Cancer 7th edition. CONCLUSION: The newly released classification American Joint Committee on Cancer 8th edition staging system demonstrated a poor to moderate ability to predict prognosis of patients undergoing liver resection for perihilar cholangiocarcinoma, which was only slightly better than the previous edition. Further refinements are needed to improve the prognostic ability of the American Joint Committee on Cancer staging system for perihilar cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"benefit radiotherapy 90 patients resected intrahepatic cholangiocarcinoma concurrent lymph node metastases purpose evaluate role radiotherapy patients resected intrahepatic cholangiocarcinoma concurrent macroscopic abdominal lymph node metastases methods identified 90 patients resected intrahepatic cholangiocarcinoma concurrent regional lymph node metastases treated 1999 2008 thereinto 24 patients received local limited external beam radiotherapy classified radiotherapy group median total dose 50 gy range 34 60 gy fractions 2 gy five times week remaining 66 patients receive external beam radiotherapy classified non radiotherapy group studied survival tumor response radiotherapy demonstrated symptoms results imaging kaplan meier method cox analysis results radiotherapy lymph nodes showed partial response nine patients 37 5 complete response nine patients 37 5 median survival 19 1 months radiotherapy group 9 5 months non radiotherapy group p 0 011 multivariate analysis showed increasing age multiple intrahepatic primary tumors higher level ca19 9 non radiotherapy group related poorer prognosis common cause death intrahepatic recurrence death resulting lymph node related complications similar two groups conclusions external beam radiotherapy seems improve prognosis patients resected intrahepatic cholangiocarcinoma concurrent macroscopic lymph node metastases pubmed","probabilities":0.9799733,"Title":"Benefit of radiotherapy for 90 patients with resected intrahepatic cholangiocarcinoma and concurrent lymph node metastases","Abstract":"PURPOSE: To evaluate the role of radiotherapy for patients with resected intrahepatic cholangiocarcinoma with concurrent macroscopic abdominal lymph node metastases. METHODS: We identified 90 patients with resected intrahepatic cholangiocarcinoma and concurrent regional lymph node metastases treated between 1999 and 2008, thereinto 24 patients received local limited external beam radiotherapy (classified as the radiotherapy group) with a median total dose of 50 Gy (range 34-60 Gy) in fractions of 2 Gy five times a week. The remaining 66 patients did not receive external beam radiotherapy (classified as the non-radiotherapy group). We studied survival and tumor response to radiotherapy, demonstrated by symptoms and results of imaging, by Kaplan-Meier method and Cox analysis. RESULTS: After radiotherapy, lymph nodes showed partial response in nine patients (37.5%) and complete response in nine patients (37.5%). Median survival was 19.1 months in the radiotherapy group and 9.5 months in the non-radiotherapy group (P = 0.011). Multivariate analysis showed that increasing age, multiple intrahepatic primary tumors, higher level of CA19-9, and non-radiotherapy group were related to a poorer prognosis. The most common cause of death was intrahepatic recurrence, and death resulting from lymph node-related complications was similar between the two groups. CONCLUSIONS: External beam radiotherapy seems to improve the prognosis of patients with resected intrahepatic cholangiocarcinoma and concurrent macroscopic lymph node metastases.","Source":"PubMed","category":"HUMAN","training_data":"Benefit of radiotherapy for 90 patients with resected intrahepatic cholangiocarcinoma and concurrent lymph node metastases PURPOSE: To evaluate the role of radiotherapy for patients with resected intrahepatic cholangiocarcinoma with concurrent macroscopic abdominal lymph node metastases. METHODS: We identified 90 patients with resected intrahepatic cholangiocarcinoma and concurrent regional lymph node metastases treated between 1999 and 2008, thereinto 24 patients received local limited external beam radiotherapy (classified as the radiotherapy group) with a median total dose of 50 Gy (range 34-60 Gy) in fractions of 2 Gy five times a week. The remaining 66 patients did not receive external beam radiotherapy (classified as the non-radiotherapy group). We studied survival and tumor response to radiotherapy, demonstrated by symptoms and results of imaging, by Kaplan-Meier method and Cox analysis. RESULTS: After radiotherapy, lymph nodes showed partial response in nine patients (37.5%) and complete response in nine patients (37.5%). Median survival was 19.1 months in the radiotherapy group and 9.5 months in the non-radiotherapy group (P = 0.011). Multivariate analysis showed that increasing age, multiple intrahepatic primary tumors, higher level of CA19-9, and non-radiotherapy group were related to a poorer prognosis. The most common cause of death was intrahepatic recurrence, and death resulting from lymph node-related complications was similar between the two groups. CONCLUSIONS: External beam radiotherapy seems to improve the prognosis of patients with resected intrahepatic cholangiocarcinoma and concurrent macroscopic lymph node metastases. PubMed","prediction_labels":"HUMAN"},{"cleaned":"efficacy safety compound tri metal stent placement malignant perihilar biliary obstruction background despite many attempts improve patency rate biliary stents patients inoperable perihilar cholangiocarcinomas longevity stents satisfactory purpose present study report technical outcomes clinical efficacy placement compound tri metal stent patients malignant perihilar biliary obstruction materials methods retrospective analysis performed medical records 26 consecutive patients inoperable malignant perihilar biliary obstruction underwent compound tri metal stent placement percutaneous transhepatic biliary drainage tube january 2012 april 2017 results placement compound tri metal stent successfully completed 26 patients technical success 100 neither procedure related mortality 30 day mortality none patients underwent additional metallic stent placement within 60 days secondary recurrent cholangitis stent occlusion successful drainage achieved 25 96 2 26 patients received compound tri metal stent patients treated compound tri metal stent placement median stent patency 145 days range 24 426 weeks median survival time 188 days range 37 1732 days conclusions placement compound tri metal stent patients malignant perihilar biliary obstruction may offer safe effective alternate technique improve biliary drainage stent patency pubmed","probabilities":0.9799733,"Title":"Efficacy and safety of compound tri-metal stent placement for malignant perihilar biliary obstruction","Abstract":"BACKGROUND: Despite many attempts to improve the patency rate of biliary stents in patients with inoperable perihilar cholangiocarcinomas, the longevity of these stents has not been satisfactory. The purpose of the present study is to report technical outcomes and clinical efficacy of the placement of compound tri-metal stent in patients with malignant perihilar biliary obstruction. MATERIALS AND METHODS: Retrospective analysis was performed of the medical records of 26 consecutive patients with inoperable malignant perihilar biliary obstruction who underwent compound tri-metal stent placement through a percutaneous transhepatic biliary drainage tube from January 2012 to April 2017. RESULTS: Placement of the compound tri-metal stent was successfully completed in all 26 patients (technical success, 100%). There was neither procedure-related mortality nor 30-day mortality. None of these patients underwent additional metallic stent placement within 60 days secondary to recurrent cholangitis or stent occlusion. Successful drainage was achieved in 25 (96.2%) of 26 patients who received a compound tri-metal stent. Patients treated with compound tri-metal stent placement had a median stent patency of 145 days (range, 24-426 weeks) and a median survival time of 188 days (range, 37-1732 days). CONCLUSIONS: Placement of compound tri-metal stent in patients with malignant perihilar biliary obstruction may offer a safe and effective alternate technique to improve biliary drainage and stent patency.","Source":"PubMed","category":"HUMAN","training_data":"Efficacy and safety of compound tri-metal stent placement for malignant perihilar biliary obstruction BACKGROUND: Despite many attempts to improve the patency rate of biliary stents in patients with inoperable perihilar cholangiocarcinomas, the longevity of these stents has not been satisfactory. The purpose of the present study is to report technical outcomes and clinical efficacy of the placement of compound tri-metal stent in patients with malignant perihilar biliary obstruction. MATERIALS AND METHODS: Retrospective analysis was performed of the medical records of 26 consecutive patients with inoperable malignant perihilar biliary obstruction who underwent compound tri-metal stent placement through a percutaneous transhepatic biliary drainage tube from January 2012 to April 2017. RESULTS: Placement of the compound tri-metal stent was successfully completed in all 26 patients (technical success, 100%). There was neither procedure-related mortality nor 30-day mortality. None of these patients underwent additional metallic stent placement within 60 days secondary to recurrent cholangitis or stent occlusion. Successful drainage was achieved in 25 (96.2%) of 26 patients who received a compound tri-metal stent. Patients treated with compound tri-metal stent placement had a median stent patency of 145 days (range, 24-426 weeks) and a median survival time of 188 days (range, 37-1732 days). CONCLUSIONS: Placement of compound tri-metal stent in patients with malignant perihilar biliary obstruction may offer a safe and effective alternate technique to improve biliary drainage and stent patency. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association shift work risk death biliary tract cancer japanese men background increasing evidence suggesting shift work involving night work may increase cancer risk methods examined association working rotating shifts risk death biliary tract cancer among japanese men participated japan collaborative cohort study 46 395 men recruited 22 224 men aged 40 65 baseline 1988 1990 reported working full time self employed included present analysis study subjects followed december 31 2009 information regarding occupation lifestyle factors collected using self administered questionnaire cox proportional hazard models used estimate hazard ratio hr 95 confidence interval ci risk death biliary tract cancer relation shift work results mean 17 year follow observed 94 biliary tract cancer deaths including 23 deaths gallbladder cancer 71 deaths extrahepatic bile duct cancer overall shift work associated statistically non significant increase risk biliary tract cancer hr 1 50 95 ci 0 81 2 77 among rotating shift workers analysis limited extrahepatic bile duct cancer significant association appeared multivariable adjusted hr 1 93 95 ci 1 00 3 72 rotating shift workers conclusion data indicate shift work may associated increased risk death extrahepatic bile duct cancer cohort japanese men association gallbladder cancer remains unclear small number deaths pubmed","probabilities":0.9799733,"Title":"Association between shift work and the risk of death from biliary tract cancer in Japanese men","Abstract":"BACKGROUND: There is increasing evidence suggesting that shift work involving night work may increase cancer risk. METHODS: We examined the association between working rotating shifts and the risk of death from biliary tract cancer among Japanese men who participated in the Japan Collaborative Cohort Study. Of the 46,395 men recruited, 22,224 men aged 40-65 at baseline (1988-1990) who reported working full-time or were self-employed were included in the present analysis. The study subjects were followed through December 31, 2009. Information regarding occupation and lifestyle factors was collected using a self-administered questionnaire. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for the risk of death from biliary tract cancer in relation to shift work. RESULTS: During a mean 17-year follow-up, we observed 94 biliary tract cancer deaths, including 23 deaths from gallbladder cancer and 71 deaths from extrahepatic bile duct cancer. Overall, shift work was associated with a statistically non-significant increase in the risk of biliary tract cancer, with an HR of 1.50 (95 % CI: 0.81-2.77), among rotating shift workers. When the analysis was limited to extrahepatic bile duct cancer, a significant association appeared, with a multivariable-adjusted HR of 1.93 (95 % CI: 1.00-3.72) for rotating shift workers. CONCLUSION: Our data indicate that shift work may be associated with increased risk of death from extrahepatic bile duct cancer in this cohort of Japanese men. The association with gallbladder cancer remains unclear because of the small number of deaths.","Source":"PubMed","category":"HUMAN","training_data":"Association between shift work and the risk of death from biliary tract cancer in Japanese men BACKGROUND: There is increasing evidence suggesting that shift work involving night work may increase cancer risk. METHODS: We examined the association between working rotating shifts and the risk of death from biliary tract cancer among Japanese men who participated in the Japan Collaborative Cohort Study. Of the 46,395 men recruited, 22,224 men aged 40-65 at baseline (1988-1990) who reported working full-time or were self-employed were included in the present analysis. The study subjects were followed through December 31, 2009. Information regarding occupation and lifestyle factors was collected using a self-administered questionnaire. Cox proportional hazard models were used to estimate the hazard ratio (HR) and 95 % confidence interval (CI) for the risk of death from biliary tract cancer in relation to shift work. RESULTS: During a mean 17-year follow-up, we observed 94 biliary tract cancer deaths, including 23 deaths from gallbladder cancer and 71 deaths from extrahepatic bile duct cancer. Overall, shift work was associated with a statistically non-significant increase in the risk of biliary tract cancer, with an HR of 1.50 (95 % CI: 0.81-2.77), among rotating shift workers. When the analysis was limited to extrahepatic bile duct cancer, a significant association appeared, with a multivariable-adjusted HR of 1.93 (95 % CI: 1.00-3.72) for rotating shift workers. CONCLUSION: Our data indicate that shift work may be associated with increased risk of death from extrahepatic bile duct cancer in this cohort of Japanese men. The association with gallbladder cancer remains unclear because of the small number of deaths. PubMed","prediction_labels":"HUMAN"},{"cleaned":"contemporary surgical approach hilar cholangiocarcinoma background diagnostic therapeutic approach hilar cholangiocarcinoma thus prognosis changed significantly last two decades nonetheless hilar cholangiocarcinoma presents complex surgical challenge objectives assess outcome radical approach management types iii iv hilar cholangiocarcinoma methods conducted retrospective single center study preoperative diagnosis based ultrasound computed tomography selective percutaneous cholangiography without tissue diagnosis surgery radical included en bloc liver extrahepatic biliary tree hilar lymph nodes resection followed biliary reconstruction hepaticojejunostomy results fifteen patients mean age 49 years range 24 72 managed accordingly anatomic classification biliary involvement bismuth corlette type iiia n 4 type iiib n 3 type iv n 8 surgical procedures performed included four right hepatic lobectomies five left hepatic lobectomies six trisegmentectomies extended caudate lobe complete negative resection margins ro accomplished 12 cases 80 regional lymph node metastases detected five cases two perioperative mortalities long term follow mean 30 months range 6 72 revealed local recurrences two cases distant metastases three local distant two cases eleven patients alive 6 without evidence disease overall 2 5 year survival 78 38 respectively conclusions selected patients aggressive surgical approach hilar cholangiocarcinoma justified result long term survival pubmed","probabilities":0.7966102,"Title":"Contemporary surgical approach to hilar cholangiocarcinoma","Abstract":"BACKGROUND: The diagnostic and therapeutic approach to hilar cholangiocarcinoma and thus the prognosis have changed significantly over the last two decades. Nonetheless, hilar cholangiocarcinoma presents a complex surgical challenge. OBJECTIVES: To assess the outcome of the radical approach for the management of types III and IV hilar cholangiocarcinoma. METHODS: We conducted a retrospective single-center study. Preoperative diagnosis was based on ultrasound, computed tomography and selective percutaneous cholangiography without tissue diagnosis. Surgery was radical and included en-bloc liver, extrahepatic biliary tree and hilar lymph nodes resection, followed by biliary reconstruction with hepaticojejunostomy. RESULTS: Fifteen patients (mean age 49 years, range 24-72) were managed accordingly. Anatomic classification of the biliary involvement was Bismuth-Corlette type IIIA (n=4), type IIIB (n=3) and type IV (n=8). The surgical procedures performed included four right hepatic lobectomies, five left hepatic lobectomies and six trisegmentectomies (all extended to the caudate lobe). Complete negative resection margins (RO) were accomplished in 12 cases (80%). Regional lymph node metastases were detected in five cases. There were two perioperative mortalities. Long-term follow-up (mean 30 months, range 6-72) revealed local recurrences in two cases, distant metastases in three, and both local and distant in two cases. Eleven patients are alive and 6 are without evidence of disease. The overall 2- and 5-year survival is 78% and 38% respectively. CONCLUSIONS: In selected patients the aggressive surgical approach to hilar cholangiocarcinoma is justified and can result in long-term survival.","Source":"PubMed","category":"HUMAN","training_data":"Contemporary surgical approach to hilar cholangiocarcinoma BACKGROUND: The diagnostic and therapeutic approach to hilar cholangiocarcinoma and thus the prognosis have changed significantly over the last two decades. Nonetheless, hilar cholangiocarcinoma presents a complex surgical challenge. OBJECTIVES: To assess the outcome of the radical approach for the management of types III and IV hilar cholangiocarcinoma. METHODS: We conducted a retrospective single-center study. Preoperative diagnosis was based on ultrasound, computed tomography and selective percutaneous cholangiography without tissue diagnosis. Surgery was radical and included en-bloc liver, extrahepatic biliary tree and hilar lymph nodes resection, followed by biliary reconstruction with hepaticojejunostomy. RESULTS: Fifteen patients (mean age 49 years, range 24-72) were managed accordingly. Anatomic classification of the biliary involvement was Bismuth-Corlette type IIIA (n=4), type IIIB (n=3) and type IV (n=8). The surgical procedures performed included four right hepatic lobectomies, five left hepatic lobectomies and six trisegmentectomies (all extended to the caudate lobe). Complete negative resection margins (RO) were accomplished in 12 cases (80%). Regional lymph node metastases were detected in five cases. There were two perioperative mortalities. Long-term follow-up (mean 30 months, range 6-72) revealed local recurrences in two cases, distant metastases in three, and both local and distant in two cases. Eleven patients are alive and 6 are without evidence of disease. The overall 2- and 5-year survival is 78% and 38% respectively. CONCLUSIONS: In selected patients the aggressive surgical approach to hilar cholangiocarcinoma is justified and can result in long-term survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"major hepatectomy without pancreatoduodenectomy advanced gallbladder cancer background indications major hepatectomy gallbladder cancer either without pancreatoduodenectomy remain controversial clinical value extended procedures evaluated study methods patients underwent major hepatectomy gallbladder cancer 1996 2016 identified prospectively compiled database postoperative outcomes overall survival compared patients undergoing major hepatectomy alone combined pancreatoduodenectomy hpd results seventy nine patients underwent major hepatectomy alone 38 patients hpd patients underwent hpd likely t4 disease p 0 001 nodal metastasis p 0 015 periaortic nodal metastasis p 0 006 less likely receive adjuvant therapy p 0 006 hpd associated high incidence grade iii higher complications p 0 002 death p 0 037 overall survival longer patients underwent major hepatectomy alone patients underwent hpd median survival time 32 versus 10 months p 0 001 multivariable analysis surgery early period 1996 2006 p 0 002 pathological t4 disease p 0 005 distant metastasis p 0 001 associated shorter overall survival cystic duct tumour p 0 002 longer overall survival conclusion major hepatectomy alone gallbladder cancer contributes favourable overall survival low morbidity mortality whereas hpd associated poor overall survival high morbidity mortality rates hpd may eradicate locally spreading gallbladder cancer however indication procedure questioned oncological viewpoint pubmed","probabilities":0.9799733,"Title":"Major hepatectomy with or without pancreatoduodenectomy for advanced gallbladder cancer","Abstract":"BACKGROUND: The indications for major hepatectomy for gallbladder cancer either with or without pancreatoduodenectomy remain controversial. The clinical value of these extended procedures was evaluated in this study. METHODS: Patients who underwent major hepatectomy for gallbladder cancer between 1996 and 2016 were identified from a prospectively compiled database. Postoperative outcomes and overall survival were compared between patients undergoing major hepatectomy alone or combined with pancreatoduodenectomy (HPD). RESULTS: Seventy-nine patients underwent major hepatectomy alone and 38 patients had HPD. The patients who underwent HPD were more likely to have T4 disease (P < 0·001), nodal metastasis (P = 0·015) and periaortic nodal metastasis (P = 0·006), but were less likely to receive adjuvant therapy (P = 0·006). HPD was associated with a high incidence of grade III or higher complications (P = 0·002) and death (P = 0·037). Overall survival was longer in patients who underwent major hepatectomy alone than in patients who underwent HPD (median survival time 32 versus 10 months; P < 0·001). In multivariable analysis, surgery in the early period (1996-2006) (P = 0·002), pathological T4 disease (P = 0·005) and distant metastasis (P < 0·001) were associated with shorter overall survival, and cystic duct tumour (P = 0·002) with longer overall survival. CONCLUSION: Major hepatectomy alone for gallbladder cancer contributes to favourable overall survival with low morbidity and mortality, whereas HPD is associated with poor overall survival and high morbidity and mortality rates. HPD may eradicate locally spreading gallbladder cancer; however, the indication for the procedure is questioned from an oncological viewpoint.","Source":"PubMed","category":"HUMAN","training_data":"Major hepatectomy with or without pancreatoduodenectomy for advanced gallbladder cancer BACKGROUND: The indications for major hepatectomy for gallbladder cancer either with or without pancreatoduodenectomy remain controversial. The clinical value of these extended procedures was evaluated in this study. METHODS: Patients who underwent major hepatectomy for gallbladder cancer between 1996 and 2016 were identified from a prospectively compiled database. Postoperative outcomes and overall survival were compared between patients undergoing major hepatectomy alone or combined with pancreatoduodenectomy (HPD). RESULTS: Seventy-nine patients underwent major hepatectomy alone and 38 patients had HPD. The patients who underwent HPD were more likely to have T4 disease (P < 0·001), nodal metastasis (P = 0·015) and periaortic nodal metastasis (P = 0·006), but were less likely to receive adjuvant therapy (P = 0·006). HPD was associated with a high incidence of grade III or higher complications (P = 0·002) and death (P = 0·037). Overall survival was longer in patients who underwent major hepatectomy alone than in patients who underwent HPD (median survival time 32 versus 10 months; P < 0·001). In multivariable analysis, surgery in the early period (1996-2006) (P = 0·002), pathological T4 disease (P = 0·005) and distant metastasis (P < 0·001) were associated with shorter overall survival, and cystic duct tumour (P = 0·002) with longer overall survival. CONCLUSION: Major hepatectomy alone for gallbladder cancer contributes to favourable overall survival with low morbidity and mortality, whereas HPD is associated with poor overall survival and high morbidity and mortality rates. HPD may eradicate locally spreading gallbladder cancer; however, the indication for the procedure is questioned from an oncological viewpoint. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparative analysis left versus right sided resection klatskin tumor surgery lesion side considered prognostic factor background achievement negative margins goal curative intent surgery hilar cholangiocarcinoma study analyzed factors affecting survival hilar cholangiocarcinoma patients compared short long term outcomes left right sided resections methods one hundred five patients 124 diagnosed klatskin tumors underwent major liver resection sixty one patients underwent right sided resections right group whereas 44 underwent left sided resections left group perioperative morbidity perioperative mortality overall disease free survival compared groups results morbidity mortality higher right group 59 8 2 respectively left group 38 6 2 3 respectively p 0 005 frequent cause death liver failure r0 rate 75 4 right 61 4 left group 5 year survival rate 42 8 right 35 3 left group p 0 05 patients left group frequently developed local recurrence 87 vs 69 right group conclusion lesion side impacts outcome right resections still cause significant morbidity related extensive parenchymal sacrifice associated better long term survival right hepatic pedicle resection enables better radicality compared left resections stn","probabilities":0.9799733,"Title":"Comparative Analysis Of Left- Versus Right-Sided Resection In Klatskin Tumor Surgery: Can Lesion Side Be Considered A Prognostic Factor?","Abstract":"Background: Achievement of negative margins is the goal of curative intent surgery for hilar cholangiocarcinoma. This study analyzed factors affecting survival in hilar cholangiocarcinoma patients and compared short- and long-term outcomes of left- and right-sided resections. \r\n\r\n Methods: One hundred and five patients out of 124 diagnosed with Klatskin tumors underwent major liver resection. Sixty-one patients underwent right-sided resections (right group), whereas 44 underwent left-sided resections (left group). Perioperative morbidity, perioperative mortality, and overall and disease-free survival were compared between the groups. \r\n\r\n Results: Morbidity and mortality were higher in the right group (59 and 8.2%, respectively) than in the left group (38.6 and 2.3%, respectively) (p < 0.005). The most frequent cause of death was liver failure. The R0 rate was 75.4% in the right and 61.4% in the left group. The 5-year survival rate was 42.8% in the right and 35.3% in the left group (p < 0.05). Patients in the left group more frequently developed local recurrence (87 vs. 69% in the right group). \r\n\r\n Conclusion: Lesion side impacts outcome: right resections still cause significant morbidity related to extensive parenchymal sacrifice but are associated with better long-term survival because right hepatic pedicle resection enables better radicality compared with left resections.","Source":"STN","category":"HUMAN","training_data":"Comparative Analysis Of Left- Versus Right-Sided Resection In Klatskin Tumor Surgery: Can Lesion Side Be Considered A Prognostic Factor? Background: Achievement of negative margins is the goal of curative intent surgery for hilar cholangiocarcinoma. This study analyzed factors affecting survival in hilar cholangiocarcinoma patients and compared short- and long-term outcomes of left- and right-sided resections. \r\n\r\n Methods: One hundred and five patients out of 124 diagnosed with Klatskin tumors underwent major liver resection. Sixty-one patients underwent right-sided resections (right group), whereas 44 underwent left-sided resections (left group). Perioperative morbidity, perioperative mortality, and overall and disease-free survival were compared between the groups. \r\n\r\n Results: Morbidity and mortality were higher in the right group (59 and 8.2%, respectively) than in the left group (38.6 and 2.3%, respectively) (p < 0.005). The most frequent cause of death was liver failure. The R0 rate was 75.4% in the right and 61.4% in the left group. The 5-year survival rate was 42.8% in the right and 35.3% in the left group (p < 0.05). Patients in the left group more frequently developed local recurrence (87 vs. 69% in the right group). \r\n\r\n Conclusion: Lesion side impacts outcome: right resections still cause significant morbidity related to extensive parenchymal sacrifice but are associated with better long-term survival because right hepatic pedicle resection enables better radicality compared with left resections. STN","prediction_labels":"HUMAN"},{"cleaned":"racial socioeconomic disparities incidence rates survival gallbladder cancer united states abstract available google scholar","probabilities":0.9799733,"Title":"Racial And Socioeconomic Disparities In The Incidence Rates And Survival Of Gallbladder Cancer In The United States","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Racial And Socioeconomic Disparities In The Incidence Rates And Survival Of Gallbladder Cancer In The United States Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"impact detection bias risk gastrointestinal cancer subsites type 2 diabetes mellitus background type 2 diabetes mellitus t2dm may risk factor gastrointestinal gi cancers variations study designs observational studies may yielded biased results due detection bias furthermore differences risk gi cancer subsites extensively evaluated aimed determine risk gi cancer subsites patients t2dm affected detection bias methods matched cohort study performed using ncr pharmo database new users 1 non insulin anti diabetic drug 1998 2011 matched non diabetic controls year birth sex time database entry index cox regression analyses performed without lag period estimate hazard ratios hrs gi cancer subsites covariables included age sex use drugs history hospitalisation results increased risk gi cancer observed t2dm patients hr 1 5 95 confidence interval ci 1 3 1 7 compared controls attenuated 1 year lagged analysis hr 1 4 95 ci 1 2 1 7 stratified subsite statistically significant increased risks pancreatic hr 4 7 95 ci 3 1 7 2 extrahepatic bile duct hr 4 2 95 ci 1 5 11 8 distal colon cancer hr 1 5 95 ci 1 1 2 1 found remained statistically significantly increased lagged analysis conclusions t2dm patients 40 increased risk gi cancer increased gi cancer risks tended weaker reducing detection bias applying 1 year lag period future observational studies therefore include sensitivity analyses bias minimised pubmed","probabilities":0.9799733,"Title":"Impact of detection bias on the risk of gastrointestinal cancer and its subsites in type 2 diabetes mellitus","Abstract":"BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for gastrointestinal (GI) cancers, but variations in study designs of observational studies may have yielded biased results due to detection bias. Furthermore, differences in risk for GI cancer subsites have not been extensively evaluated. We aimed to determine the risk of GI cancer and its subsites in patients with T2DM and how it is affected by detection bias. METHODS: A matched cohort study was performed using the NCR-PHARMO database. New-users of ≥1 non-insulin anti-diabetic drug during 1998-2011 were matched with non-diabetic controls by year of birth, sex, and time between database entry and index. Cox regression analyses were performed with and without lag-period to estimate hazard ratios (HRs) for GI cancer and its subsites. Covariables included age, sex, use of other drugs and history of hospitalisation. RESULTS: An increased risk of GI cancer was observed in T2DM patients (HR 1.5, 95% confidence interval [CI] 1.3-1.7) compared with controls, which was attenuated in the 1-year lagged analysis (HR 1.4, 95% CI 1.2-1.7). Stratified by subsite, statistically significant increased risks of pancreatic (HR 4.7, 95% CI 3.1-7.2), extrahepatic bile duct (HR 4.2, 95% CI 1.5-11.8) and distal colon cancer (HR 1.5, 95% CI 1.1-2.1) were found, which remained statistically significantly increased in the lagged analysis. CONCLUSIONS: T2DM patients had a 40% increased risk of GI cancer. Increased GI cancer risks tended to be weaker when reducing detection bias by applying a 1-year lag-period. Future observational studies should therefore include sensitivity analyses in which this bias is minimised.","Source":"PubMed","category":"HUMAN","training_data":"Impact of detection bias on the risk of gastrointestinal cancer and its subsites in type 2 diabetes mellitus BACKGROUND: Type 2 diabetes mellitus (T2DM) may be a risk factor for gastrointestinal (GI) cancers, but variations in study designs of observational studies may have yielded biased results due to detection bias. Furthermore, differences in risk for GI cancer subsites have not been extensively evaluated. We aimed to determine the risk of GI cancer and its subsites in patients with T2DM and how it is affected by detection bias. METHODS: A matched cohort study was performed using the NCR-PHARMO database. New-users of ≥1 non-insulin anti-diabetic drug during 1998-2011 were matched with non-diabetic controls by year of birth, sex, and time between database entry and index. Cox regression analyses were performed with and without lag-period to estimate hazard ratios (HRs) for GI cancer and its subsites. Covariables included age, sex, use of other drugs and history of hospitalisation. RESULTS: An increased risk of GI cancer was observed in T2DM patients (HR 1.5, 95% confidence interval [CI] 1.3-1.7) compared with controls, which was attenuated in the 1-year lagged analysis (HR 1.4, 95% CI 1.2-1.7). Stratified by subsite, statistically significant increased risks of pancreatic (HR 4.7, 95% CI 3.1-7.2), extrahepatic bile duct (HR 4.2, 95% CI 1.5-11.8) and distal colon cancer (HR 1.5, 95% CI 1.1-2.1) were found, which remained statistically significantly increased in the lagged analysis. CONCLUSIONS: T2DM patients had a 40% increased risk of GI cancer. Increased GI cancer risks tended to be weaker when reducing detection bias by applying a 1-year lag-period. Future observational studies should therefore include sensitivity analyses in which this bias is minimised. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cyp1a1 gstm1 gstt1 tp53 polymorphisms risk gallbladder cancer bolivians plurinational state bolivia bolivia high incidence rate gallbladder cancer gbc however genetic environmental risk factors gbc development well understood aimed assess whether cytochrome p450 cyp1a1 glutathione transferase mu 1 gstm1 theta 1 gstt1 tumor suppressor protein p53 tp53 genetic polymorphisms modulate gbc susceptibility bolivians case control study covered 32 patients gbc 86 healthy subjects gbc diagnosed basis histological analysis tissues instituto de gastroenterologia boliviano japones igbj healthy subjects members staff igbj distributions cyp1a1 rs1048943 tp53 rs1042522 polymorphisms assayed using pcr restriction fragment length polymorphism assay gstm1 gstt1 deletion polymorphisms detected multiplex pcr assay frequency gstm1 null genotype significantly higher gbc patients healthy subjects odds ratio 2 35 95 confidence interval ci 1 03 5 37 age adjusted 3 53 95 ci 1 29 9 66 age sex adjusted 3 40 95 ci 1 24 9 34 significant differences observed frequencies cyp1a1 gstt1 tp53 polymorphisms two groups gstm1 null genotype associated increased gbc risk bolivians additional studies larger control case populations warranted confirm association gstm1 deletion polymorphism gbc risk suggested present study pubmed","probabilities":0.88235295,"Title":"CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians","Abstract":"The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study.","Source":"PubMed","category":"ANIMAL","training_data":"CYP1A1, GSTM1, GSTT1 and TP53 Polymorphisms and Risk of Gallbladder Cancer in Bolivians The Plurinational State of Bolivia (Bolivia) has a high incidence rate of gallbladder cancer (GBC). However, the genetic and environmental risk factors for GBC development are not well understood. We aimed to assess whether or not cytochrome P450 (CYP1A1), glutathione S-transferase mu 1 (GSTM1), theta 1 (GSTT1) and tumor suppressor protein p53 (TP53) genetic polymorphisms modulate GBC susceptibility in Bolivians. This case-control study covered 32 patients with GBC and 86 healthy subjects. GBC was diagnosed on the basis of histological analysis of tissues at the Instituto de Gastroenterologia Boliviano-Japones (IGBJ); the healthy subjects were members of the staff at the IGBJ. Distributions of the CYP1A1 rs1048943 and TP53 rs1042522 polymorphisms were assayed using PCR-restriction fragment length polymorphism assay. GSTM1 and GSTT1 deletion polymorphisms were detected by a multiplex PCR assay. The frequency of the GSTM1 null genotype was significantly higher in GBC patients than in the healthy subjects (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.03-5.37; age-adjusted OR, 3.53; 95% CI, 1.29-9.66; age- and sex-adjusted OR, 3.40; 95% CI, 1.24-9.34). No significant differences were observed in the frequencies of CYP1A1, GSTT1, or TP53 polymorphisms between the two groups. The GSTM1 null genotype was associated with increased GBC risk in Bolivians. Additional studies with larger control and case populations are warranted to confirm the association between the GSTM1 deletion polymorphism and GBC risk suggested in the present study. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact marital status survival among patients cholangiocarcinoma although prognostic value marital status implicated many cancers prognostic impact cholangiocarcinoma yet determined aim study examine association marital status cholangiocarcinoma survival included 8 776 extrahepatic cholangiocarcinoma cases 1 352 intrahepatic cholangiocarcinoma cases 1973 2013 surveillance epidemiology end results database found widowed patients likely female aged 70 low income areas multivariate analysis indicated marital status independent prognostic factor extrahepatic cholangiocarcinoma patients subgroup analysis suggested widowed status independently predicted poor survival regional stage older patients intrahepatic cholangiocarcinoma conclude marital status valuable prognostic factor cholangiocarcinoma widowed patients greater risk death others stn","probabilities":0.9799733,"Title":"Impact Of Marital Status On Survival Among Patients With Cholangiocarcinoma","Abstract":"Although the prognostic value of marital status has been implicated in many cancers, its prognostic impact on cholangiocarcinoma has not yet been determined. The aim of this study was to examine the association between marital status and cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from the Surveillance, Epidemiology, and End Results database. We found widowed patients were more likely to be female, aged more than 70, and from low income areas. Multivariate analysis indicated that marital status was an independent prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis suggested the widowed status independently predicted poor survival at regional stage and in older patients with intrahepatic cholangiocarcinoma. To conclude, marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed patients are at greater risk of death than others.","Source":"STN","category":"HUMAN","training_data":"Impact Of Marital Status On Survival Among Patients With Cholangiocarcinoma Although the prognostic value of marital status has been implicated in many cancers, its prognostic impact on cholangiocarcinoma has not yet been determined. The aim of this study was to examine the association between marital status and cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from the Surveillance, Epidemiology, and End Results database. We found widowed patients were more likely to be female, aged more than 70, and from low income areas. Multivariate analysis indicated that marital status was an independent prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis suggested the widowed status independently predicted poor survival at regional stage and in older patients with intrahepatic cholangiocarcinoma. To conclude, marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed patients are at greater risk of death than others. STN","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma epidemiology risk factors diagnosis surgical management intrahepatic cholangiocarcinoma icc least common form cholangiocarcinomas rare hepatobiliary malignancy arises epithelial cells intrahepatic bile ducts incidence icc rising global scale last twenty years may reflect true increase trend earlier detection disease well recognized causative risk factors association viral metabolic factors icc pathogenesis increasingly identified recently surgical resection currently feasible modality curative ability resectability curability remain low high invasiveness icc predisposes tumors multifocality node metastasis vascular invasions leading poor long term survival resection role liver transplantation controversial locoregional treatments systematic therapies may provide survival benefits especially patients unresectable advanced tumors present review discussed epidemiology risk factors surgical multimodal management iccs mainly focused outcomes factors associated surgical treatment pubmed","probabilities":0.9799733,"Title":"Intrahepatic cholangiocarcinoma: Epidemiology, risk factors, diagnosis and surgical management","Abstract":"Intrahepatic cholangiocarcinoma (ICC), the least common form of cholangiocarcinomas, is a rare hepatobiliary malignancy that arises from the epithelial cells of the intrahepatic bile ducts. The incidence of ICC has been rising in the global scale over the last twenty years, which may reflect both a true increase and the trend of earlier detection of the disease. Other than some well recognized causative risk factors, the association between viral and metabolic factors and ICC pathogenesis has been increasingly identified recently. Surgical resection is currently the only feasible modality with a curative ability, but the resectability and curability remain low. The high invasiveness of ICC predisposes the tumors to multifocality, node metastasis and vascular invasions, leading to poor long-term survival after resection. The role of liver transplantation is controversial, while locoregional treatments and systematic therapies may provide survival benefits, especially in patients with unresectable and advanced tumors. The present review discussed the epidemiology, risk factors, surgical and multimodal management of ICCs, which mainly focused on the outcomes and factors associated with surgical treatment.","Source":"PubMed","category":"HUMAN","training_data":"Intrahepatic cholangiocarcinoma: Epidemiology, risk factors, diagnosis and surgical management Intrahepatic cholangiocarcinoma (ICC), the least common form of cholangiocarcinomas, is a rare hepatobiliary malignancy that arises from the epithelial cells of the intrahepatic bile ducts. The incidence of ICC has been rising in the global scale over the last twenty years, which may reflect both a true increase and the trend of earlier detection of the disease. Other than some well recognized causative risk factors, the association between viral and metabolic factors and ICC pathogenesis has been increasingly identified recently. Surgical resection is currently the only feasible modality with a curative ability, but the resectability and curability remain low. The high invasiveness of ICC predisposes the tumors to multifocality, node metastasis and vascular invasions, leading to poor long-term survival after resection. The role of liver transplantation is controversial, while locoregional treatments and systematic therapies may provide survival benefits, especially in patients with unresectable and advanced tumors. The present review discussed the epidemiology, risk factors, surgical and multimodal management of ICCs, which mainly focused on the outcomes and factors associated with surgical treatment. PubMed","prediction_labels":"HUMAN"},{"cleaned":"efficacy stereotactic body radiotherapy unresectable recurrent cholangiocarcinoma meta analysis systematic review purpose non surgical treatment including stereotactic body radiation therapy sbrt used practically alternative modalities unresectable recurrent cholangiocarcinoma cc performed systematic review meta analysis examine efficacy sbrt patients methods embase pubmed medline cochrane library databases searched systematically october 2017 primary endpoint 1 year local control lc rate 1 year overall survival os response rates grade 3 toxicities assessed secondary endpoints results eleven studies 226 patients included prescribed median sbrt dose 45 range 30 55 gy 3 5 fractions pooled 1 year lc rate 81 8 95 confidence interval ci 69 4 89 9 studies using equivalent dose 2 gy per fraction eqd2 71 3 gy 2 74 7 95 ci 57 1 86 7 studies using eqd2 71 3 gy 2 median os 13 6 range 10 35 5 months pooled 1 year os rate 53 8 95 ci 44 9 62 5 pooled 1 year lc rate 78 6 95 ci 69 0 85 8 common toxicity duodenal ulcer gastric ulcer available studies acute incidence grade 3 less 10 late incidence 10 20 conclusions sbrt feasible treatment option respect achieving high lc unresectable recurrent cc gastrointestinal toxicity acceptable remains obstacle related dose escalation pubmed","probabilities":0.9799733,"Title":"Efficacy of stereotactic body radiotherapy for unresectable or recurrent cholangiocarcinoma: a meta-analysis and systematic review","Abstract":"PURPOSE: Non-surgical treatment including stereotactic body radiation therapy (SBRT) have been used practically as alternative modalities for unresectable or recurrent cholangiocarcinoma (CC). We performed a systematic review and meta-analysis to examine the efficacy of SBRT for such patients. METHODS: Embase, PubMed, MEDLINE, and Cochrane library databases were searched systematically until October 2017. Primary endpoint was 1‑year local control (LC) rate; 1‑year overall survival (OS), response rates, and grade ≥3 toxicities were assessed as secondary endpoints. RESULTS: Eleven studies (226 patients) were included. The prescribed median SBRT dose was 45 (range 30-55) Gy in 3-5 fractions. The pooled 1‑year LC rate was 81.8% (95% confidence interval [CI] 69.4-89.9%) in the studies using an equivalent dose in 2 Gy per fraction (EQD2) ≥71.3 Gy(2) and 74.7% (95% CI 57.1-86.7%) in the studies using an EQD2 <71.3 Gy(2). The median OS was 13.6 (range 10-35.5) months. The pooled 1‑year OS rate was 53.8% (95% CI 44.9-62.5%) and the pooled 1‑year LC rate was 78.6% (95% CI 69.0-85.8%). Most common toxicity was duodenal ulcer and gastric ulcer in available studies, with the acute incidence of grade ≥3 of less than 10% and the late incidence of 10-20%. CONCLUSIONS: SBRT was a feasible treatment option with respect to achieving a high LC for unresectable or recurrent CC. Gastrointestinal toxicity is acceptable, but remains an obstacle related to dose escalation.","Source":"PubMed","category":"HUMAN","training_data":"Efficacy of stereotactic body radiotherapy for unresectable or recurrent cholangiocarcinoma: a meta-analysis and systematic review PURPOSE: Non-surgical treatment including stereotactic body radiation therapy (SBRT) have been used practically as alternative modalities for unresectable or recurrent cholangiocarcinoma (CC). We performed a systematic review and meta-analysis to examine the efficacy of SBRT for such patients. METHODS: Embase, PubMed, MEDLINE, and Cochrane library databases were searched systematically until October 2017. Primary endpoint was 1‑year local control (LC) rate; 1‑year overall survival (OS), response rates, and grade ≥3 toxicities were assessed as secondary endpoints. RESULTS: Eleven studies (226 patients) were included. The prescribed median SBRT dose was 45 (range 30-55) Gy in 3-5 fractions. The pooled 1‑year LC rate was 81.8% (95% confidence interval [CI] 69.4-89.9%) in the studies using an equivalent dose in 2 Gy per fraction (EQD2) ≥71.3 Gy(2) and 74.7% (95% CI 57.1-86.7%) in the studies using an EQD2 <71.3 Gy(2). The median OS was 13.6 (range 10-35.5) months. The pooled 1‑year OS rate was 53.8% (95% CI 44.9-62.5%) and the pooled 1‑year LC rate was 78.6% (95% CI 69.0-85.8%). Most common toxicity was duodenal ulcer and gastric ulcer in available studies, with the acute incidence of grade ≥3 of less than 10% and the late incidence of 10-20%. CONCLUSIONS: SBRT was a feasible treatment option with respect to achieving a high LC for unresectable or recurrent CC. Gastrointestinal toxicity is acceptable, but remains an obstacle related to dose escalation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"differential protein expression marks transition infection opisthorchis viverrini cholangiocarcinoma parts southeast asia highest incidence intrahepatic cholangiocarcinoma cca world infection liver fluke opisthorchis viverrini ov ov associated cca culmination chronic ov infection persistent production growth factors cytokines associated persistent inflammation endure years ov infected individuals prior transitioning cca isobaric labeling tandem mass spectrometry liver tissue hamster model cca used compare protein expression profiles inflammed tissue ovinfected cancerous versus cancerous tissue ov induced cca immunohistochemistry immunoblotting used verify dysregulated proteins animal model human tissue identified 154 dysregulated proteins marked transition ov infection ov induced cca e proteins dysregulated carcinogenesis ov infection verification dysregulated proteins resected liver tissue humans ov associated cca showed numerous parallels protein dysregulation human animal models ov induced cca identify potential circulating markers cca dysregulated proteins compared proteins isolated exosomes secreted human cca cell line kku055 27 proteins identified dysregulated cca present exosomes data form basis potential diagnostic biomarkers human ov associated cca profile protein dysregulation observed chronic ovinfection ov induced cca provides insight etiology infection induced inflammation related cancer stn","probabilities":0.9467213,"Title":"Differential Protein Expression Marks The Transition From Infection With Opisthorchis Viverrini To Cholangiocarcinoma","Abstract":"Parts of Southeast Asia have the highest incidence of intrahepatic cholangiocarcinoma (CCA) in the world because of infection by the liver fluke Opisthorchis viverrini (Ov). Ov-associated CCA is the culmination of chronic Ov-infection, with the persistent production of the growth factors and cytokines associated with persistent inflammation, which can endure for years in Ov-infected individuals prior to transitioning to CCA. Isobaric labeling and tandem mass spectrometry of liver tissue from a hamster model of CCA was used to compare protein expression profiles from inflammed tissue (Ovinfected but not cancerous) versus cancerous tissue (Ov-induced CCA). Immunohistochemistry and immunoblotting were used to verify dysregulated proteins in the animal model and in human tissue. We identified 154 dysregulated proteins that marked the transition from Ov-infection to Ov-induced CCA, i.e. proteins dysregulated during carcinogenesis but not Ov-infection. The verification of dysregulated proteins in resected liver tissue from humans with Ov-associated CCA showed the numerous parallels in protein dysregulation between human and animal models of Ov-induced CCA. To identify potential circulating markers for CCA, dysregulated proteins were compared with proteins isolated from exosomes secreted by a human CCA cell line (KKU055) and 27 proteins were identified as dysregulated in CCA and present in exosomes. These data form the basis of potential diagnostic biomarkers for human Ov-associated CCA. The profile of protein dysregulation observed during chronic Ovinfection and then in Ov-induced CCA provides insight into the etiology of an infection-induced inflammation-related cancer.","Source":"STN","category":"ANIMAL","training_data":"Differential Protein Expression Marks The Transition From Infection With Opisthorchis Viverrini To Cholangiocarcinoma Parts of Southeast Asia have the highest incidence of intrahepatic cholangiocarcinoma (CCA) in the world because of infection by the liver fluke Opisthorchis viverrini (Ov). Ov-associated CCA is the culmination of chronic Ov-infection, with the persistent production of the growth factors and cytokines associated with persistent inflammation, which can endure for years in Ov-infected individuals prior to transitioning to CCA. Isobaric labeling and tandem mass spectrometry of liver tissue from a hamster model of CCA was used to compare protein expression profiles from inflammed tissue (Ovinfected but not cancerous) versus cancerous tissue (Ov-induced CCA). Immunohistochemistry and immunoblotting were used to verify dysregulated proteins in the animal model and in human tissue. We identified 154 dysregulated proteins that marked the transition from Ov-infection to Ov-induced CCA, i.e. proteins dysregulated during carcinogenesis but not Ov-infection. The verification of dysregulated proteins in resected liver tissue from humans with Ov-associated CCA showed the numerous parallels in protein dysregulation between human and animal models of Ov-induced CCA. To identify potential circulating markers for CCA, dysregulated proteins were compared with proteins isolated from exosomes secreted by a human CCA cell line (KKU055) and 27 proteins were identified as dysregulated in CCA and present in exosomes. These data form the basis of potential diagnostic biomarkers for human Ov-associated CCA. The profile of protein dysregulation observed during chronic Ovinfection and then in Ov-induced CCA provides insight into the etiology of an infection-induced inflammation-related cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"efficacy endoscopic 3 branched partial stent stent drainage using self expandable metallic stents patients unresectable hilar biliary carcinoma background treatment biliary stricture crucially important continuing stable chemotherapy unresectable biliary carcinoma however consensus regarding use hilar biliary drainage study examined efficacy endoscopic 3 branched biliary drainage using self expandable metallic stents semss patients unresectable malignant hilar biliary stricture hbs methods total 77 patients unresectable hbs treated sems chemotherapy retrospectively reviewed 59 patients cholangiocarcinoma 18 patients gallbladder carcinoma patients divided 2 groups 4 3 branched group 2 1 branched group compared respect duration stent patency overall survival results comparison patients baseline characteristics showed significant differences 4 3 branched group 2 1 branched group neither duration patency survival time exhibited significant differences 2 groups although among patients achieving disease control duration patency period survival time 4 3 branched group significantly higher observed 2 1 branched group p 0 0231 0 0466 conclusions use endoscopic 3 branched biliary drainage sems may improve duration patency patients hbs pubmed","probabilities":0.9799733,"Title":"Efficacy of Endoscopic Over 3-branched Partial Stent-in-Stent Drainage Using Self-expandable Metallic Stents in Patients With Unresectable Hilar Biliary Carcinoma","Abstract":"BACKGROUND: The treatment of biliary stricture is crucially important for continuing stable chemotherapy for unresectable biliary carcinoma; however, there is no consensus regarding the use of hilar biliary drainage. In this study, we examined the efficacy of endoscopic over 3-branched biliary drainage using self-expandable metallic stents (SEMSs) in patients with unresectable malignant hilar biliary stricture (HBS). METHODS: A total of 77 patients with unresectable HBS treated with a SEMS and chemotherapy were retrospectively reviewed. There were 59 patients with cholangiocarcinoma and 18 patients with gallbladder carcinoma. The patients were divided into 2 groups (4- or 3-branched group and 2- or 1-branched group) and compared with respect to the duration of stent patency and overall survival. RESULTS: A comparison of the patients' baseline characteristics showed no significant differences between the 4- or 3-branched group and the 2- or 1-branched group. Neither the duration of patency nor survival time exhibited significant differences between the 2 groups, although, among the patients achieving disease control , the duration of patency period and survival time of the 4- or 3-branched group were significantly higher than those observed in the 2- or 1-branched group (P=0.0231 and 0.0466). CONCLUSIONS: The use of endoscopic over 3-branched biliary drainage with a SEMS may improve the duration of patency in patients with HBS.","Source":"PubMed","category":"HUMAN","training_data":"Efficacy of Endoscopic Over 3-branched Partial Stent-in-Stent Drainage Using Self-expandable Metallic Stents in Patients With Unresectable Hilar Biliary Carcinoma BACKGROUND: The treatment of biliary stricture is crucially important for continuing stable chemotherapy for unresectable biliary carcinoma; however, there is no consensus regarding the use of hilar biliary drainage. In this study, we examined the efficacy of endoscopic over 3-branched biliary drainage using self-expandable metallic stents (SEMSs) in patients with unresectable malignant hilar biliary stricture (HBS). METHODS: A total of 77 patients with unresectable HBS treated with a SEMS and chemotherapy were retrospectively reviewed. There were 59 patients with cholangiocarcinoma and 18 patients with gallbladder carcinoma. The patients were divided into 2 groups (4- or 3-branched group and 2- or 1-branched group) and compared with respect to the duration of stent patency and overall survival. RESULTS: A comparison of the patients' baseline characteristics showed no significant differences between the 4- or 3-branched group and the 2- or 1-branched group. Neither the duration of patency nor survival time exhibited significant differences between the 2 groups, although, among the patients achieving disease control , the duration of patency period and survival time of the 4- or 3-branched group were significantly higher than those observed in the 2- or 1-branched group (P=0.0231 and 0.0466). CONCLUSIONS: The use of endoscopic over 3-branched biliary drainage with a SEMS may improve the duration of patency in patients with HBS. PubMed","prediction_labels":"HUMAN"},{"cleaned":"novel diagnostic prognostic biomarkers biliary tract cancer introduction worldwide incidence biliary tract carcinoma btc tumours bile ducts gall bladder continues rise potentially curative treatment remaining surgical resection transplantation possible minority patients late presentation paucity effective treatments mandate development techniques early lesion detection areas covered article reviews currently available biomarkers diagnosis prognosis btc well recently published studies describing novel serum bile urinary biomarkers expert opinion incorporation novel analysis techniques digital image analysis fluorescence situ hybridization existing management algorithms enhances accuracy brush cytology taken time therapeutic endoscopy however key goal discovery reliable non invasive biomarkers high sensitivity specificity recent advances gene sequencing expression clonal evolution tumour heterogeneity cancers advance understanding btc tumour biology facilitate biomarker discovery pubmed","probabilities":0.9799733,"Title":"Novel diagnostic and prognostic biomarkers in biliary tract cancer","Abstract":"INTRODUCTION: The worldwide incidence of biliary tract carcinoma (BTC, tumours of the bile ducts and gall-bladder) continues to rise, with the only potentially curative treatment remaining surgical resection or transplantation, possible in only a minority of patients. Late presentation and a paucity of effective treatments mandate the development of techniques for early lesion detection. AREAS COVERED: This article reviews currently available biomarkers for the diagnosis and prognosis of BTC, as well as recently published studies describing novel serum, bile and urinary biomarkers. EXPERT OPINION: The incorporation of novel analysis techniques, such as digital image analysis and fluorescence in situ hybridization, into existing management algorithms enhances the accuracy of brush cytology taken at the time of therapeutic endoscopy. However, a key goal is the discovery of reliable non-invasive biomarkers with high sensitivity and specificity. Recent advances in gene sequencing and expression, clonal evolution and tumour heterogeneity in other cancers should advance understanding of BTC tumour biology and facilitate biomarker discovery.","Source":"PubMed","category":"HUMAN","training_data":"Novel diagnostic and prognostic biomarkers in biliary tract cancer INTRODUCTION: The worldwide incidence of biliary tract carcinoma (BTC, tumours of the bile ducts and gall-bladder) continues to rise, with the only potentially curative treatment remaining surgical resection or transplantation, possible in only a minority of patients. Late presentation and a paucity of effective treatments mandate the development of techniques for early lesion detection. AREAS COVERED: This article reviews currently available biomarkers for the diagnosis and prognosis of BTC, as well as recently published studies describing novel serum, bile and urinary biomarkers. EXPERT OPINION: The incorporation of novel analysis techniques, such as digital image analysis and fluorescence in situ hybridization, into existing management algorithms enhances the accuracy of brush cytology taken at the time of therapeutic endoscopy. However, a key goal is the discovery of reliable non-invasive biomarkers with high sensitivity and specificity. Recent advances in gene sequencing and expression, clonal evolution and tumour heterogeneity in other cancers should advance understanding of BTC tumour biology and facilitate biomarker discovery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathologic analysis prognosis extrahepatic bile duct cancer microscopic positive ductal margin background fate microscopic positive ductal margin mpdm extrahepatic bile duct ehbd cancer unclear purpose study analyse clinicopathological features ehbd cancer mpdm identify prognostic factors associated survival methods 1995 2007 retrospective analysis 464 patients undergone surgical resection ehbd cancer conducted clinicopathological factors likely influence survival assessed using univariate multivariate analysis results one hundred twenty four patients mpdm included invasive carcinoma ic n 85 carcinoma situ cis high grade dysplasia hgd n 39 median survival ms r0 r1 cis hgd r1 ic 41 months 29 months 18 months respectively adverse prognostic factors ic resection margin hr 1 66 95 confidence intervals cis 1 06 2 59 p 0 026 use adjuvant chemoradiotherapy hr 1 57 95 cis 1 04 2 39 p 0 033 adjuvant chemoradiotherapy beneficial patients mpdm ic 5 year survival rate 19 7 compared 2 8 p 0 011 conclusions presence mpdm important prognostic factor ehbd cancer ductal resection margin positive discrimination ic cis hgd important stn","probabilities":0.9799733,"Title":"Clinicopathologic Analysis And Prognosis Of Extrahepatic Bile Duct Cancer With A Microscopic Positive Ductal Margin","Abstract":"Background: The fate of a microscopic positive ductal margin (MPDM) of extrahepatic bile duct (EHBD) cancer is unclear. The purpose of this study was to analyse the clinicopathological features of EHBD cancer with MPDM and to identify the prognostic factors associated with survival. \r\n\r\n Methods: Between 1995 and 2007, a retrospective analysis of 464 patients who had undergone surgical resection for EHBD cancer was conducted. Clinicopathological factors likely to influence survival were assessed using univariate and multivariate analysis. \r\n\r\n Results: One hundred twenty-four patients had MPDM which included invasive carcinoma (IC) (n =85) and carcinoma in situ (CIS)/ high-grade dysplasia (HGD) (n = 39). The median survival (MS) of R0, R1 as CIS/ HGD, and R1 as IC were 41 months, 29 months, and 18 months, respectively. Adverse prognostic factors were 'IC' on the resection margin [HR = 1.66, 95% confidence intervals (CIs) 1.06-2.59, P = 0.026], and no use of adjuvant chemoradiotherapy (HR = 1.57, 95% CIs 1.04-2.39, P = 0.033). Adjuvant chemoradiotherapy was beneficial in patients with MPDM as IC (5-year survival rate 19.7 compared with 2.8%, P = 0.011). \r\n\r\n Conclusions: The presence of MPDM is an important prognostic factor in EHBD cancer. When a ductal resection margin is positive, discrimination between 'IC' and 'CIS/ HGD' is important.","Source":"STN","category":"HUMAN","training_data":"Clinicopathologic Analysis And Prognosis Of Extrahepatic Bile Duct Cancer With A Microscopic Positive Ductal Margin Background: The fate of a microscopic positive ductal margin (MPDM) of extrahepatic bile duct (EHBD) cancer is unclear. The purpose of this study was to analyse the clinicopathological features of EHBD cancer with MPDM and to identify the prognostic factors associated with survival. \r\n\r\n Methods: Between 1995 and 2007, a retrospective analysis of 464 patients who had undergone surgical resection for EHBD cancer was conducted. Clinicopathological factors likely to influence survival were assessed using univariate and multivariate analysis. \r\n\r\n Results: One hundred twenty-four patients had MPDM which included invasive carcinoma (IC) (n =85) and carcinoma in situ (CIS)/ high-grade dysplasia (HGD) (n = 39). The median survival (MS) of R0, R1 as CIS/ HGD, and R1 as IC were 41 months, 29 months, and 18 months, respectively. Adverse prognostic factors were 'IC' on the resection margin [HR = 1.66, 95% confidence intervals (CIs) 1.06-2.59, P = 0.026], and no use of adjuvant chemoradiotherapy (HR = 1.57, 95% CIs 1.04-2.39, P = 0.033). Adjuvant chemoradiotherapy was beneficial in patients with MPDM as IC (5-year survival rate 19.7 compared with 2.8%, P = 0.011). \r\n\r\n Conclusions: The presence of MPDM is an important prognostic factor in EHBD cancer. When a ductal resection margin is positive, discrimination between 'IC' and 'CIS/ HGD' is important. STN","prediction_labels":"HUMAN"},{"cleaned":"lncrna meg3 inhibits cell proliferation invasion modulating bmi1 rnf2 cholangiocarcinoma cholangiocarcinoma cca mortal cancer gradually increasing incidences world whereas effective diagnosis treatment disease still lacking classical long noncoding rna lncrna maternally expressed gene 3 meg3 reported exhibit pivotal regulatory roles occurrence development various digestive system tumors nevertheless clinical relevance biological function meg3 cca remain largely unclear study meg3 expression significantly downregulated cca tissues cells comparison nontumor controls respectively downexpression prominently associated advanced tnm stage lymph node invasion poor survival moreover decreased meg3 independent forecaster poor prognosis cca patients functionally meg3 overexpression inhibited cca growth vitro vivo enhanced meg3 also suppressed migration invasion cclp 1 qbc939 cells reversing epithelial mesenchymal transition emt process contrary proliferation metastasis emt facilitated via knocking meg3 addition expression b lymphoma mo mlv insertion region 1 bmi1 ring finger protein 2 impacted gain loss meg3 furthermore malignant processes induced meg3 knockdown rescued means silencing bmi1 data suggested meg3 caused tumor suppressive effects partly mediating polycomb repressive complex 1 findings elucidate meg3 exerts critical functions cca development likely acts promising tumor indicator intervention target cca stn","probabilities":0.9467213,"Title":"Lncrna-Meg3 Inhibits Cell Proliferation And Invasion By Modulating Bmi1/Rnf2 In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a mortal cancer with gradually increasing incidences all over the world, whereas effective diagnosis and treatment for this disease are still lacking. As a classical long noncoding RNA (lncRNA), maternally expressed gene 3 (MEG3) has been reported to exhibit pivotal regulatory roles in the occurrence and development of various digestive system tumors. Nevertheless, the clinical relevance and biological function of MEG3 in CCA remain largely unclear. In this study, MEG3 expression was significantly downregulated in both CCA tissues and cells in comparison with that in nontumor controls, respectively, and this downexpression was prominently associated with advanced TNM stage, lymph node invasion, and poor survival. Moreover, decreased MEG3 was an independent forecaster of poor prognosis for CCA patients. Functionally, MEG3 overexpression inhibited CCA growth in vitro and in vivo. Enhanced MEG3 also suppressed migration and invasion of CCLP-1 and QBC939 cells by reversing epithelial-mesenchymal transition (EMT) process. On the contrary, the proliferation, metastasis, and EMT were facilitated via knocking down MEG3. In addition, the expression of B lymphoma Mo-MLV insertion region 1 (Bmi1) and RING finger protein 2 was impacted by gain or loss of MEG3, furthermore, the malignant processes induced by MEG3 knockdown were rescued by means of silencing Bmi1. These data suggested that MEG3 caused tumor suppressive effects partly through mediating polycomb repressive complex 1. Our findings elucidate that MEG3 exerts critical functions in CCA development and likely acts as a promising tumor indicator or intervention target for CCA.","Source":"STN","category":"ANIMAL","training_data":"Lncrna-Meg3 Inhibits Cell Proliferation And Invasion By Modulating Bmi1/Rnf2 In Cholangiocarcinoma Cholangiocarcinoma (CCA) is a mortal cancer with gradually increasing incidences all over the world, whereas effective diagnosis and treatment for this disease are still lacking. As a classical long noncoding RNA (lncRNA), maternally expressed gene 3 (MEG3) has been reported to exhibit pivotal regulatory roles in the occurrence and development of various digestive system tumors. Nevertheless, the clinical relevance and biological function of MEG3 in CCA remain largely unclear. In this study, MEG3 expression was significantly downregulated in both CCA tissues and cells in comparison with that in nontumor controls, respectively, and this downexpression was prominently associated with advanced TNM stage, lymph node invasion, and poor survival. Moreover, decreased MEG3 was an independent forecaster of poor prognosis for CCA patients. Functionally, MEG3 overexpression inhibited CCA growth in vitro and in vivo. Enhanced MEG3 also suppressed migration and invasion of CCLP-1 and QBC939 cells by reversing epithelial-mesenchymal transition (EMT) process. On the contrary, the proliferation, metastasis, and EMT were facilitated via knocking down MEG3. In addition, the expression of B lymphoma Mo-MLV insertion region 1 (Bmi1) and RING finger protein 2 was impacted by gain or loss of MEG3, furthermore, the malignant processes induced by MEG3 knockdown were rescued by means of silencing Bmi1. These data suggested that MEG3 caused tumor suppressive effects partly through mediating polycomb repressive complex 1. Our findings elucidate that MEG3 exerts critical functions in CCA development and likely acts as a promising tumor indicator or intervention target for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"clinicopathological differences t2 gallbladder cancer according tumor location aimed identify clinicopathological differences factors affecting survival outcomes stage t2a t2b gallbladder cancer gbc validate oncological benefits regional lymphadenectomy hepatic resection patients single center study enrolled patients diagnosed pathologically confirmed t2 gbc underwent curative resection january 1995 december 2017 eighty two patients t2a 50 t2b gbcs identified clinical information retrospectively collected medical records analyzed five year overall survival rates 96 8 80 7 t2a t2b groups respectively p 007 three 5 year survival rates among patients t2 gbc without lymph node metastasis 97 2 94 4 81 3 81 3 respectively p 029 difference survival rates 2 groups according whether hepatic resection performed p 320 however t2b group underwent hepatic resection demonstrated better survival rate p 029 t2b group multiple recurrence patterns t2a group lymph nodes common site groups multivariate analysis revealed lymph node metastasis vascular invasion tumor location significant independent prognostic factors hepatic resection always necessary patients peritoneal side gbc considering clinicopathological features recurrence patterns systematic treatment plan including radical resection adjuvant treatment established hepatic side gbc stn","probabilities":0.9799733,"Title":"Clinicopathological Differences In T2 Gallbladder Cancer According To Tumor Location","Abstract":"We aimed to identify clinicopathological differences and factors affecting survival outcomes of stage T2a and T2b gallbladder cancer (GBC) and validate the oncological benefits of regional lymphadenectomy and hepatic resection in these patients. This single-center study enrolled patients who were diagnosed with pathologically confirmed T2 GBC and underwent curative resection between January 1995 and December 2017. Eighty-two patients with T2a and 50 with T2b GBCs were identified, and clinical information was retrospectively collected from medical records and analyzed. Five-year overall survival rates were 96.8% and 80.7% in T2a and T2b groups, respectively (P = .007). Three- and 5-year survival rates among all patients with T2 GBC without and with lymph node metastasis were 97.2% and 94.4% and 81.3% and 81.3%, respectively (P = .029). There was no difference in survival rates between the 2 groups according to whether hepatic resection was performed (P = .320). However, in the T2b group, those who underwent hepatic resection demonstrated a better survival rate than those who did not (P = .029). The T2b group had more multiple recurrence patterns than the T2a group, and the lymph nodes were the most common site in both groups. Multivariate analysis revealed that lymph node metastasis, vascular invasion, and tumor location were significant independent prognostic factors. Hepatic resection was not always necessary in patients with peritoneal-side GBC. Considering clinicopathological features and recurrence patterns, a systematic treatment plan, including radical resection and adjuvant treatment, should be established for hepatic-side GBC.","Source":"STN","category":"HUMAN","training_data":"Clinicopathological Differences In T2 Gallbladder Cancer According To Tumor Location We aimed to identify clinicopathological differences and factors affecting survival outcomes of stage T2a and T2b gallbladder cancer (GBC) and validate the oncological benefits of regional lymphadenectomy and hepatic resection in these patients. This single-center study enrolled patients who were diagnosed with pathologically confirmed T2 GBC and underwent curative resection between January 1995 and December 2017. Eighty-two patients with T2a and 50 with T2b GBCs were identified, and clinical information was retrospectively collected from medical records and analyzed. Five-year overall survival rates were 96.8% and 80.7% in T2a and T2b groups, respectively (P = .007). Three- and 5-year survival rates among all patients with T2 GBC without and with lymph node metastasis were 97.2% and 94.4% and 81.3% and 81.3%, respectively (P = .029). There was no difference in survival rates between the 2 groups according to whether hepatic resection was performed (P = .320). However, in the T2b group, those who underwent hepatic resection demonstrated a better survival rate than those who did not (P = .029). The T2b group had more multiple recurrence patterns than the T2a group, and the lymph nodes were the most common site in both groups. Multivariate analysis revealed that lymph node metastasis, vascular invasion, and tumor location were significant independent prognostic factors. Hepatic resection was not always necessary in patients with peritoneal-side GBC. Considering clinicopathological features and recurrence patterns, a systematic treatment plan, including radical resection and adjuvant treatment, should be established for hepatic-side GBC. STN","prediction_labels":"HUMAN"},{"cleaned":"detection nrg1 gene fusions solid tumors purpose nrg1 gene fusions rare potentially actionable oncogenic drivers present solid tumors details regarding incidence gene rearrangements lacking assessed incidence nrg1 fusions across multiple tumor types described fusion partners experimental design tumor specimens submitted molecular profiling clinical laboratory improvement amendments clia certified genomics laboratory underwent fusion testing anchored multiplex pcr targeted rna sequencing retrospectively identified overall tumor specific incidence noted specific fusion partner results 21 858 tumor specimens profiled september 2015 december 2018 41 cases 0 2 harbored nrg1 fusion multiple fusion partners identified fusion events seen across tumor types greatest incidence non small cell lung cancer nsclc 25 though represented 0 3 nsclc cases tested tumor types harboring nrg1 fusion included gallbladder cancer renal cell carcinoma bladder cancer ovarian cancer pancreatic cancer breast cancer neuroendocrine tumor sarcoma colorectal cancer conclusions nrg1 fusions detected low incidence across multiple tumor types significant heterogeneity fusion partner see related commentary dimou camidge p 4865 pubmed","probabilities":0.962963,"Title":"Detection of NRG1 Gene Fusions in Solid Tumors","Abstract":"PURPOSE: NRG1 gene fusions are rare but potentially actionable oncogenic drivers that are present in some solid tumors. Details regarding the incidence of these gene rearrangements are lacking. Here, we assessed the incidence of NRG1 fusions across multiple tumor types and described fusion partners. EXPERIMENTAL DESIGN: Tumor specimens submitted for molecular profiling at a Clinical Laboratory Improvement Amendments (CLIA)-certified genomics laboratory and that underwent fusion testing by anchored multiplex PCR for targeted RNA sequencing were retrospectively identified. The overall and tumor-specific incidence was noted, as was the specific fusion partner. RESULTS: Out of 21,858 tumor specimens profiled from September 2015 to December 2018, 41 cases (0.2%) harbored an NRG1 fusion. Multiple fusion partners were identified. Fusion events were seen across tumor types. The greatest incidence was in non-small cell lung cancer (NSCLC, 25), though this represented only 0.3% of NSCLC cases tested. Other tumor types harboring an NRG1 fusion included gallbladder cancer, renal cell carcinoma, bladder cancer, ovarian cancer, pancreatic cancer, breast cancer, neuroendocrine tumor, sarcoma, and colorectal cancer. CONCLUSIONS: NRG1 fusions can be detected at a low incidence across multiple tumor types with significant heterogeneity in fusion partner.See related commentary by Dimou and Camidge, p. 4865.","Source":"PubMed","category":"ANIMAL","training_data":"Detection of NRG1 Gene Fusions in Solid Tumors PURPOSE: NRG1 gene fusions are rare but potentially actionable oncogenic drivers that are present in some solid tumors. Details regarding the incidence of these gene rearrangements are lacking. Here, we assessed the incidence of NRG1 fusions across multiple tumor types and described fusion partners. EXPERIMENTAL DESIGN: Tumor specimens submitted for molecular profiling at a Clinical Laboratory Improvement Amendments (CLIA)-certified genomics laboratory and that underwent fusion testing by anchored multiplex PCR for targeted RNA sequencing were retrospectively identified. The overall and tumor-specific incidence was noted, as was the specific fusion partner. RESULTS: Out of 21,858 tumor specimens profiled from September 2015 to December 2018, 41 cases (0.2%) harbored an NRG1 fusion. Multiple fusion partners were identified. Fusion events were seen across tumor types. The greatest incidence was in non-small cell lung cancer (NSCLC, 25), though this represented only 0.3% of NSCLC cases tested. Other tumor types harboring an NRG1 fusion included gallbladder cancer, renal cell carcinoma, bladder cancer, ovarian cancer, pancreatic cancer, breast cancer, neuroendocrine tumor, sarcoma, and colorectal cancer. CONCLUSIONS: NRG1 fusions can be detected at a low incidence across multiple tumor types with significant heterogeneity in fusion partner.See related commentary by Dimou and Camidge, p. 4865. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epigenetic silencing tumor suppressor gene cdkn1a oncogenic long non coding rna snhg1 cholangiocarcinoma cholangiocarcinoma cca frequently observed biliary tract malignancy low survival rate addition constrained treatment options nevertheless fundamental molecular phenomenon underlying malignant progression cca quite ambiguous recently long non coding rnas lncrnas found significant regulatory functions several human cancers herein figured lncrna snhg1 substantially enhanced expression cca capable acting oncogenic molecule cca revealed data snhg1 knockdown extensively inhibited cca cell migration well proliferation vitro vivo addition accordance findings rna seq analysis snhg1 knockdown exhibited significant impact target genes linked cell migration regulation cell proliferation addition apoptotic phenomenon mechanistic manner also showed snhg1 bound histone methyltransferase enhancer zeste homolog 2 ezh2 regarded catalytic subunit polycomb repressive complex 2 prc2 extremely conserved protein complex regulating gene expression help methylating lysine 27 histone h3 specifying histone alteration pattern target genes including cdkn1a result altered cca cell biology data verified major function epigenetic regulation snhg1 cca oncogenesis addition likely function target cca interruption stn","probabilities":0.9467213,"Title":"Epigenetic Silencing Of Tumor Suppressor Gene Cdkn1A By Oncogenic Long Non-Coding Rna Snhg1 In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options; nevertheless, the fundamental molecular phenomenon underlying malignant progression of CCA is quite ambiguous. Recently long non-coding RNAs (lncRNAs) have been found to have significant regulatory functions in several human cancers. Herein, we have figured out that lncRNA SNHG1, with substantially enhanced expression in CCA, is capable of acting as the oncogenic molecule of CCA. As revealed by our data, SNHG1 knockdown extensively inhibited CCA cell migration as well as proliferation in vitro and in vivo. In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. These data verified a major function of the epigenetic regulation of SNHG1 in CCA oncogenesis, in addition to its likely function as a target for CCA interruption.","Source":"STN","category":"ANIMAL","training_data":"Epigenetic Silencing Of Tumor Suppressor Gene Cdkn1A By Oncogenic Long Non-Coding Rna Snhg1 In Cholangiocarcinoma Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options; nevertheless, the fundamental molecular phenomenon underlying malignant progression of CCA is quite ambiguous. Recently long non-coding RNAs (lncRNAs) have been found to have significant regulatory functions in several human cancers. Herein, we have figured out that lncRNA SNHG1, with substantially enhanced expression in CCA, is capable of acting as the oncogenic molecule of CCA. As revealed by our data, SNHG1 knockdown extensively inhibited CCA cell migration as well as proliferation in vitro and in vivo. In addition, in accordance with the findings of the RNA-Seq analysis, SNHG1 knockdown exhibited a significant impact on the target genes that were linked to cell migration and regulation of cell proliferation, in addition to the apoptotic phenomenon. In a mechanistic manner, we also showed that SNHG1 bound to the histone methyltransferase enhancer of the zeste homolog 2 (EZH2, which is regarded as the catalytic subunit of the polycomb repressive complex 2 (PRC2), which is an extremely conserved protein complex regulating gene expression with the help of methylating lysine 27 on histone H3), specifying the histone alteration pattern on the target genes, including CDKN1A, and, as a result, altered the CCA cell biology. These data verified a major function of the epigenetic regulation of SNHG1 in CCA oncogenesis, in addition to its likely function as a target for CCA interruption. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic comparison 7th 8th editions american joint committee cancer staging system intrahepatic cholangiocarcinoma background several important changes made 8th edition american joint committee cancer ajcc tumor staging system intrahepatic cholangiocarcinoma icc assessed prognostic impact new tumor staging system compared 7th edition methods retrospective single institution study performed 626 patients underwent r0 resection icc 20 year period results anatomical resection concurrent bile duct resection performed 571 91 2 62 9 9 patients respectively cumulative tumor recurrence patient survival rates 40 6 73 3 1 year 66 7 43 8 3 years 73 6 30 4 5 years 74 4 20 3 10 years respectively independent prognostic factors tumor recurrence patient survival multiple tumors carbohydrate antigen 19 9 200 u ml tumor size 5 cm direct invasion extrahepatic structure lymph node metastasis tumor node metastasis stages 7th versus 8th editions concordance index 0 615 0 625 tumor recurrence 0 626 0 628 patient survival respectively conclusions 8th edition ajcc staging system appears provide high prognostic contrast stage categories except t3 however overall prognostic performance 8th edition markedly improved 7th edition pubmed","probabilities":0.9799733,"Title":"Prognostic comparison of the 7th and 8th editions of the American Joint Committee on Cancer staging system for intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Several important changes were made to the 8th edition of the American Joint Committee on Cancer (AJCC) tumor staging system for intrahepatic cholangiocarcinoma (ICC). We assessed the prognostic impact of this new tumor staging system compared to the 7th edition. METHODS: A retrospective single-institution study was performed with 626 patients who underwent R0 resection for ICC over 20-year period. RESULTS: Anatomical resection and concurrent bile duct resection were performed in 571 (91.2%) and 62 (9.9%) patients, respectively. Cumulative tumor recurrence and patient survival rates were 40.6% and 73.3% at 1 year; 66.7% and 43.8% at 3 years; 73.6% and 30.4% at 5 years; and 74.4% and 20.3% at 10 years, respectively. Independent prognostic factors for tumor recurrence and patient survival were multiple tumors, carbohydrate antigen 19-9 >200 U/ml, tumor size >5 cm, direct invasion to extrahepatic structure, and lymph node metastasis. For tumor-node-metastasis stages in the 7th versus the 8th editions, concordance index was 0.615 and 0.625 for tumor recurrence and 0.626 and 0.628 for patient survival, respectively. CONCLUSIONS: The 8th edition of the AJCC staging system appears to provide high prognostic contrast for T stage categories, except for T3. However, overall prognostic performance of the 8th edition was not markedly improved over the 7th edition.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic comparison of the 7th and 8th editions of the American Joint Committee on Cancer staging system for intrahepatic cholangiocarcinoma BACKGROUND: Several important changes were made to the 8th edition of the American Joint Committee on Cancer (AJCC) tumor staging system for intrahepatic cholangiocarcinoma (ICC). We assessed the prognostic impact of this new tumor staging system compared to the 7th edition. METHODS: A retrospective single-institution study was performed with 626 patients who underwent R0 resection for ICC over 20-year period. RESULTS: Anatomical resection and concurrent bile duct resection were performed in 571 (91.2%) and 62 (9.9%) patients, respectively. Cumulative tumor recurrence and patient survival rates were 40.6% and 73.3% at 1 year; 66.7% and 43.8% at 3 years; 73.6% and 30.4% at 5 years; and 74.4% and 20.3% at 10 years, respectively. Independent prognostic factors for tumor recurrence and patient survival were multiple tumors, carbohydrate antigen 19-9 >200 U/ml, tumor size >5 cm, direct invasion to extrahepatic structure, and lymph node metastasis. For tumor-node-metastasis stages in the 7th versus the 8th editions, concordance index was 0.615 and 0.625 for tumor recurrence and 0.626 and 0.628 for patient survival, respectively. CONCLUSIONS: The 8th edition of the AJCC staging system appears to provide high prognostic contrast for T stage categories, except for T3. However, overall prognostic performance of the 8th edition was not markedly improved over the 7th edition. PubMed","prediction_labels":"HUMAN"},{"cleaned":"usefulness pre treatment serum ca19 9 concentration prediction prognosis patients intrahepatic bile duct tumours abstract introduction serum concentration carbohydrate antigen 19 9 ca19 9 related survival patients cholangiocarcinoma cca evaluated cut value serum ca19 9 define predictive management strategies patients cca method three hundred forty one 341 patients retrospectively reviewed regional hepatobiliary centre liverpool uk hospital integrated database used extract clinical laboratory data receiver operating characteristic curve roc serum concentration ca19 9 location tumour type treatment offered assessed cut value ca19 9 providing optimal prognosis used evaluate differences survival patients using kaplan meier survival log rank test results one hundred sixty four 48 patients valid pre treatment ca19 9 measurements among treatment groups biliary stent placed 67 41 surgical resection 43 26 2 chemotherapy 36 22 0 18 11 supportive care site lesion roc ca19 9 0 74 95 ci 0 62 0 84 sensitivity 80 9 specificity 60 0 p 0 0002 prognosis intrahepatic disease roc hilar lesions 0 62 95 ci 0 51 0 71 sensitivity 90 2 specificity 36 1 p 0 05 treatment modality surgical resection showed significant relationship pre treatment ca19 9 value roc 0 75 95 ci 0 60 0 87 serum concentration 34 iu ml defined cut predictive prognosis surgical resection sensitivity 76 9 specificity 73 3 p 0 001 median survival patients surgical resection serum ca19 9 34 iu ml 18 months whereas value 34 iu ml 5 year survival 80 conclusion serum ca19 9 concentration useful predictor prognosis patients intrahepatic lesions well undergoing resection ihbd tumours validation cut value requires studies google scholar","probabilities":0.9799733,"Title":"Usefulness Of Pre-Treatment Serum Ca19-9 Concentration In Prediction Of Prognosis For Patients With Intrahepatic Bile Duct Tumours","Abstract":"Abstract\nIntroduction Serum concentration of Carbohydrate Antigen 19-9 (CA19-9) has been related to survival of patients with Cholangiocarcinoma (CCA). We evaluated the cut-off value of serum CA19–9 to define predictive management strategies in patients with CCA.\nMethod Three hundred and forty-one (341) Patients were retrospectively reviewed at a regional hepatobiliary centre in Liverpool, UK. The hospital integrated database was used to extract clinical and laboratory data. The receiver operating characteristic curve (ROC) of serum concentration of CA19–9 by location of tumour and type of treatment offered were assessed. The cut-off value of CA19–9 providing optimal prognosis was used to evaluate differences in survival of the patients using Kaplan-Meier survival log-rank test.\nResults One hundred and sixty-four (48%) patients had valid pre-treatment CA19–9 measurements. Among treatment groups; biliary stent was placed in 67(41%); surgical resection in 43 (26.2%); chemotherapy in 36 (22.0%); while 18 (11%) had supportive care. For site of lesion, ROC for CA19–9 was 0.74 (95% CI: 0.62–0.84; sensitivity: 80.9%; specificity: 60.0%, p = 0.0002). For prognosis of intrahepatic disease and ROC for hilar lesions was 0.62 (95% CI: 0.51–0.71; sensitivity: 90.2%; specificity: 36.1%, p = 0.05). By treatment modality, surgical resection showed significant relationship with pre-treatment CA19–9 value (ROC: 0.75; 95% CI: 0.60–0.87). Serum concentration of >34 IU/ml was defined as the cut-off predictive of prognosis for those who had surgical resection (sensitivity: 76.9% and specificity: 73.3%, p = 0.001). The median survival of patients who had surgical resection with serum CA19–9 >34 IU/ml was 18 months whereas for those with a value ≤34 IU/ml, 5 year survival was 80%.\nConclusion Serum CA19–9 concentration is a useful predictor of prognosis in patients with intrahepatic lesions as well as those undergoing resection for IHBD tumours. Validation of this cut-off value requires further studies.","Source":"Google Scholar","category":"HUMAN","training_data":"Usefulness Of Pre-Treatment Serum Ca19-9 Concentration In Prediction Of Prognosis For Patients With Intrahepatic Bile Duct Tumours Abstract\nIntroduction Serum concentration of Carbohydrate Antigen 19-9 (CA19-9) has been related to survival of patients with Cholangiocarcinoma (CCA). We evaluated the cut-off value of serum CA19–9 to define predictive management strategies in patients with CCA.\nMethod Three hundred and forty-one (341) Patients were retrospectively reviewed at a regional hepatobiliary centre in Liverpool, UK. The hospital integrated database was used to extract clinical and laboratory data. The receiver operating characteristic curve (ROC) of serum concentration of CA19–9 by location of tumour and type of treatment offered were assessed. The cut-off value of CA19–9 providing optimal prognosis was used to evaluate differences in survival of the patients using Kaplan-Meier survival log-rank test.\nResults One hundred and sixty-four (48%) patients had valid pre-treatment CA19–9 measurements. Among treatment groups; biliary stent was placed in 67(41%); surgical resection in 43 (26.2%); chemotherapy in 36 (22.0%); while 18 (11%) had supportive care. For site of lesion, ROC for CA19–9 was 0.74 (95% CI: 0.62–0.84; sensitivity: 80.9%; specificity: 60.0%, p = 0.0002). For prognosis of intrahepatic disease and ROC for hilar lesions was 0.62 (95% CI: 0.51–0.71; sensitivity: 90.2%; specificity: 36.1%, p = 0.05). By treatment modality, surgical resection showed significant relationship with pre-treatment CA19–9 value (ROC: 0.75; 95% CI: 0.60–0.87). Serum concentration of >34 IU/ml was defined as the cut-off predictive of prognosis for those who had surgical resection (sensitivity: 76.9% and specificity: 73.3%, p = 0.001). The median survival of patients who had surgical resection with serum CA19–9 >34 IU/ml was 18 months whereas for those with a value ≤34 IU/ml, 5 year survival was 80%.\nConclusion Serum CA19–9 concentration is a useful predictor of prognosis in patients with intrahepatic lesions as well as those undergoing resection for IHBD tumours. Validation of this cut-off value requires further studies. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"elevation circular rna circ_0005230 facilitates cell growth metastasis via sponging mir 1238 mir 1299 cholangiocarcinoma cholangiocarcinoma cca highly malignant carcinoma high mortality rate worldwide emerging evidence indicates aberrantly expressed circular rnas circrnas functions crucial roles tumor progression work focused novel circrna circ_0005230 carcinogenesis development cca circ_0005230 levels cca specimens cells measured qrt pcr clinical implication circ_0005230 analyzed fisher exact test gain loss function assays conducted reveal effects circ_0005230 cell proliferation apoptosis migration invasion cca cells xenograft lung metastatic models constructed confirm vitro data dual luciferase reporter rescue assays carried illuminate mechanism behind regulatory actions data showed circ_0005230 elevated tumors cca cells expression tumor samples related clinical severity functionally circ_0005230 significantly facilitated cell growth clone forming ability metastatic properties inhibit cell apoptosis cca cells vivo study validated vitro results however knockdown circ_0005230 affect normal biliary epithelial hibec cell growth apoptosis mechanism investigation circ_0005230 directly sponge mir 1238 mir 1299 exert oncogenic functions overall work showed circ_0005230 might act effective therapeutic target cca stn","probabilities":0.9467213,"Title":"Elevation Of Circular Rna Circ_0005230 Facilitates Cell Growth And Metastasis Via Sponging Mir-1238 And Mir-1299 In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a highly malignant carcinoma with high mortality rate worldwide. Emerging evidence indicates that aberrantly expressed circular RNAs (circRNAs) functions crucial roles in tumor progression. In this work, we focused on a novel circRNA, circ_0005230, in carcinogenesis and development of CCA. Circ_0005230 levels in CCA specimens and cells were measured by qRT-PCR. The clinical implication of circ_0005230 was analyzed by fisher's exact test. Gain/loss of-function assays were conducted to reveal the effects of circ_0005230 on the cell proliferation, apoptosis, migration and invasion of CCA cells. Xenograft and lung metastatic models were constructed to confirm the in vitro data. Dual luciferase reporter and rescue assays were carried out to illuminate the mechanism behind the regulatory actions. As data showed, circ_0005230 was elevated in tumors and CCA cells. Its expression in tumor samples was related to clinical severity. Functionally, circ_0005230 significantly facilitated cell growth, clone-forming ability and metastatic properties and inhibit cell apoptosis in CCA cells. The in vivo study further validated the in vitro results. However, knockdown of circ_0005230 did not affect normal biliary epithelial (HIBEC) cell growth and apoptosis. For the mechanism investigation, circ_0005230 could directly sponge miR-1238 and miR-1299 to exert its oncogenic functions. Overall, this work showed that circ_0005230 might act as an effective therapeutic target for CCA.","Source":"STN","category":"ANIMAL","training_data":"Elevation Of Circular Rna Circ_0005230 Facilitates Cell Growth And Metastasis Via Sponging Mir-1238 And Mir-1299 In Cholangiocarcinoma Cholangiocarcinoma (CCA) is a highly malignant carcinoma with high mortality rate worldwide. Emerging evidence indicates that aberrantly expressed circular RNAs (circRNAs) functions crucial roles in tumor progression. In this work, we focused on a novel circRNA, circ_0005230, in carcinogenesis and development of CCA. Circ_0005230 levels in CCA specimens and cells were measured by qRT-PCR. The clinical implication of circ_0005230 was analyzed by fisher's exact test. Gain/loss of-function assays were conducted to reveal the effects of circ_0005230 on the cell proliferation, apoptosis, migration and invasion of CCA cells. Xenograft and lung metastatic models were constructed to confirm the in vitro data. Dual luciferase reporter and rescue assays were carried out to illuminate the mechanism behind the regulatory actions. As data showed, circ_0005230 was elevated in tumors and CCA cells. Its expression in tumor samples was related to clinical severity. Functionally, circ_0005230 significantly facilitated cell growth, clone-forming ability and metastatic properties and inhibit cell apoptosis in CCA cells. The in vivo study further validated the in vitro results. However, knockdown of circ_0005230 did not affect normal biliary epithelial (HIBEC) cell growth and apoptosis. For the mechanism investigation, circ_0005230 could directly sponge miR-1238 and miR-1299 to exert its oncogenic functions. Overall, this work showed that circ_0005230 might act as an effective therapeutic target for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"expression insulin like growth factor ii mrna binding protein 3 predicts early recurrence poor prognosis intrahepatic cholangiocarcinoma introduction insulin like growth factor ii mrna binding protein 3 imp3 newly identified oncofetal rna binding protein plays pivotal role regulation cell growth migration early stages embryogenesis found expressed various human cancers study elucidated clinicopathological significance imp3 expression intrahepatic cholangiocarcinoma icc methods march 1995 december 2003 61 surgically resected unifocal primary iccs studied imp3 protein expression detected immunohistochemical staining results imp3 protein expressed 25 61 iccs 41 0 addition correlating tumor grade p 0 0276 tumor stage p 0 0059 lymphovascular invasion p 0 0198 serum carbohydrate antigen 19 9 level p 0 0146 imp3 expression predicted early tumor recurrence etr p 0 0059 strong indicator worse disease free survival p 0 0001 overall survival p 0 0007 even though find imp3 expression exerted prognostic impact independent tumor stage multivariate analysis confirmed imp3 expression independent risk factor high stage tumor etr p 0 0170 p 0 0052 respectively thus contributed poor prognosis icc patients conclusions imp3 expression serve novel maker etr prognostic prediction may target adjuvant therapy patients icc tumor resection stn","probabilities":0.9467213,"Title":"Expression Of Insulin-Like Growth Factor Ii Mrna-Binding Protein 3 Predicts Early Recurrence And Poor Prognosis In Intrahepatic Cholangiocarcinoma","Abstract":"Introduction: Insulin-like growth factor-II mRNA-binding protein 3 (IMP3), a newly identified oncofetal RNA-binding protein, plays a pivotal role in the regulation of cell growth and migration during early stages of embryogenesis, and is found to be expressed in various human cancers. In this study, we elucidated the clinicopathological significance of IMP3 expression in intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: From March 1995 to December 2003, 61 surgically resected, unifocal primary ICCs were studied. IMP3 protein expression was detected by immunohistochemical staining. \r\n\r\n Results: IMP3 protein was expressed in 25 of 61 ICCs (41.0%). In addition to correlating with tumor grade (p = 0.0276), tumor stage (p = 0.0059), lymphovascular invasion (p = 0.0198), serum carbohydrate antigen 19-9 level (p = 0.0146), IMP3 expression predicted early tumor recurrence (ETR) (p = 0.0059) and was a strong indicator of worse disease-free survival (p = 0.0001) and overall survival (p = 0.0007). Even though we did not find that IMP3 expression exerted prognostic impact independent of tumor stage, multivariate analysis confirmed that IMP3 expression was an independent risk factor of high-stage tumor and ETR (p = 0.0170, and p = 0.0052, respectively), and thus it contributed to poor prognosis in ICC patients. \r\n\r\n Conclusions: IMP3 expression can serve as a novel maker for ETR and prognostic prediction, and may be a target for adjuvant therapy of patients with ICC after tumor resection.","Source":"STN","category":"HUMAN","training_data":"Expression Of Insulin-Like Growth Factor Ii Mrna-Binding Protein 3 Predicts Early Recurrence And Poor Prognosis In Intrahepatic Cholangiocarcinoma Introduction: Insulin-like growth factor-II mRNA-binding protein 3 (IMP3), a newly identified oncofetal RNA-binding protein, plays a pivotal role in the regulation of cell growth and migration during early stages of embryogenesis, and is found to be expressed in various human cancers. In this study, we elucidated the clinicopathological significance of IMP3 expression in intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: From March 1995 to December 2003, 61 surgically resected, unifocal primary ICCs were studied. IMP3 protein expression was detected by immunohistochemical staining. \r\n\r\n Results: IMP3 protein was expressed in 25 of 61 ICCs (41.0%). In addition to correlating with tumor grade (p = 0.0276), tumor stage (p = 0.0059), lymphovascular invasion (p = 0.0198), serum carbohydrate antigen 19-9 level (p = 0.0146), IMP3 expression predicted early tumor recurrence (ETR) (p = 0.0059) and was a strong indicator of worse disease-free survival (p = 0.0001) and overall survival (p = 0.0007). Even though we did not find that IMP3 expression exerted prognostic impact independent of tumor stage, multivariate analysis confirmed that IMP3 expression was an independent risk factor of high-stage tumor and ETR (p = 0.0170, and p = 0.0052, respectively), and thus it contributed to poor prognosis in ICC patients. \r\n\r\n Conclusions: IMP3 expression can serve as a novel maker for ETR and prognostic prediction, and may be a target for adjuvant therapy of patients with ICC after tumor resection. STN","prediction_labels":"ANIMAL"},{"cleaned":"cyclin d1 retinoblastoma p16 protein expression carcinoma gallbladder background cancer gallbladder relatively rare neoplasm poor prognosis exact mechanisms genesis known little information available molecular events leading labeling orphan cancer materials methods prospective case control study evaluated expression p16 prb cyclin d1 immunohistochemistry study g1 cell cycle check point possible role gallbladder carcinogenesis total 25 patients gallbladder carcinoma group 25 cholelithiasis group ii 10 normal controls enrolled results cyclin d1 expression seen 10 40 patients carcinoma cholelithiasis 2 20 normal gallbladders differences statistically significant p value 0 488 p16 expressed 12 patients carcinoma gallbladder 28 cholelithiasis however difference statistically significant p value 0 095 retinoblastoma protein found expressed 50 normal gallbladders 6 24 carcinoma 8 32 gallstones present study failed demonstrate conclusive role cyclin d1 rb p16 pathway carcinoma gallbladder conclusions positive relation observed tumor metastasis cyclind1 expression p16 nodal metastasis suggested higher cyclin d1 p16 expression may act predictive biomarker aggressive behavior gallbladder malignancies stn","probabilities":1.0,"Title":"Cyclin D1 Retinoblastoma And P16 Protein Expression In Carcinoma Of The Gallbladder","Abstract":"Background: Cancer of the gallbladder is a relatively rare neoplasm with a poor prognosis. The exact mechanisms of its genesis are not known and very little information is available on molecular events leading to labeling this as an orphan cancer. \r\n\r\n Materials and methods: In this prospective case control study we evaluated the expression of p16, pRb and cyclin D1 by immunohistochemistry to study the G1-S cell-cycle check point and its possible role in gallbladder carcinogenesis. A total of 25 patients with gallbladder carcinoma (group I), 25 with cholelithiasis (group II) and 10 normal controls. were enrolled. \r\n\r\n Results: Cyclin D1 expression was seen in 10 (40%) patients each with carcinoma and cholelithiasis while only in 2 (20%) of the normal gallbladders but differences were not statistically significant (p value=0.488). p16 was expressed in 12% patients of carcinoma of the gallbladder and 28% of cholelithiasis, however this difference was not statistically significant (p value=0.095). Retinoblastoma protein was found to be expressed in 50% of normal gallbladders and 6 (24%) of carcinoma and 8 (32%) of gallstones. The present study failed to demonstrate any conclusive role of cyclin D1/RB/ p16 pathway in carcinoma of the gallbladder. \r\n\r\n Conclusions: The positive relation observed between tumor metastasis and cyclinD1 expression and p16 with nodal metastasis suggested that higher cyclin D1/p16 expression may act as a predictive biomarker for aggressive behavior of gallbladder malignancies.","Source":"STN","category":"HUMAN","training_data":"Cyclin D1 Retinoblastoma And P16 Protein Expression In Carcinoma Of The Gallbladder Background: Cancer of the gallbladder is a relatively rare neoplasm with a poor prognosis. The exact mechanisms of its genesis are not known and very little information is available on molecular events leading to labeling this as an orphan cancer. \r\n\r\n Materials and methods: In this prospective case control study we evaluated the expression of p16, pRb and cyclin D1 by immunohistochemistry to study the G1-S cell-cycle check point and its possible role in gallbladder carcinogenesis. A total of 25 patients with gallbladder carcinoma (group I), 25 with cholelithiasis (group II) and 10 normal controls. were enrolled. \r\n\r\n Results: Cyclin D1 expression was seen in 10 (40%) patients each with carcinoma and cholelithiasis while only in 2 (20%) of the normal gallbladders but differences were not statistically significant (p value=0.488). p16 was expressed in 12% patients of carcinoma of the gallbladder and 28% of cholelithiasis, however this difference was not statistically significant (p value=0.095). Retinoblastoma protein was found to be expressed in 50% of normal gallbladders and 6 (24%) of carcinoma and 8 (32%) of gallstones. The present study failed to demonstrate any conclusive role of cyclin D1/RB/ p16 pathway in carcinoma of the gallbladder. \r\n\r\n Conclusions: The positive relation observed between tumor metastasis and cyclinD1 expression and p16 with nodal metastasis suggested that higher cyclin D1/p16 expression may act as a predictive biomarker for aggressive behavior of gallbladder malignancies. STN","prediction_labels":"HUMAN"},{"cleaned":"expression vascular endothelial growth factor vegf advanced gallbladder cancer gallbladder cancer gbc highly fatal disease poor prognosis therapeutic alternatives molecular mechanisms involved gbc pathogenesis remain poorly understood vascular endothelial growth factor vegf potent proangiogenic agent involved carcinogenesis many human tumors attractive target cancer therapy aim study characterize vegf expression advanced gallbladder cancer determine relationships clinicopathologic features utility prognostic factor vegf expression examined immunohistochemistry ihc tissue microarrays containing 224 advanced gallbladder carcinomas 39 cases chronic cholecystitis cc advanced gbc classified low high expression evaluate association vegf expression level clinical variables statistical analysis performed using univariate analyses significance level p 0 05 survival analysis performed kaplan meier method log rank test high expression vegf observed 183 224 81 tumors 2 39 5 1 chronic cholecystitis p 0 0001 vegf expression significant relationship clinical pathological features included histological grade tnm stage p 0 05 moreover 5 year survival analysis indicated high expression vegf associated poor prognosis patients advanced gallbladder cancer p 0 0116 results indicate vegf highly expressed gallbladder cancer correlates poor prognostic suggesting vegf expression used biomarker predicting malignant behavior identify subset patients may benefit anti vegf therapies google scholar","probabilities":0.8684211,"Title":"Expression Of Vascular Endothelial Growth Factor A (Vegf-A) In Advanced Gallbladder Cancer","Abstract":"Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. The Vascular Endothelial Growth Factor A (VEGF) is a potent proangiogenic agent involved in the carcinogenesis of many human tumors and it is an attractive target for cancer therapy. The aim of this study was characterize VEGF expression in advanced gallbladder cancer and determine it's relationships with clinicopathologic features and utility as a prognostic factor. VEGF expression was examined by immunohistochemistry (IHC) in tissue microarrays containing 224 advanced gallbladder carcinomas and 39 cases of chronic cholecystitis (CC). The advanced GBC were classified as low or high expression to evaluate the association of VEGF expression level with clinical variables. Statistical analysis was performed using univariate analyses with a significance level of P<0.05; survival analysis was performed by the Kaplan- Meier method with the log-rank test. High expression of VEGF was observed in 183 of 224 (81%) tumors and 2 of 39 (5.1%) of chronic cholecystitis (P<0.0001). The VEGF expression had a significant relationship with clinical or pathological features included histological grade and TNM stage (P<0.05). Moreover, 5-year survival analysis indicated that high expression of VEGF is associated with a poor prognosis in patients with advanced gallbladder cancer (P = 0.0116). Our results indicate that VEGF is highly expressed in gallbladder cancer and correlates with poor prognostic, suggesting that VEGF expression could be used as a biomarker for predicting malignant behavior and to identify a subset of patients who may benefit from anti-VEGF therapies.","Source":"Google Scholar","category":"HUMAN","training_data":"Expression Of Vascular Endothelial Growth Factor A (Vegf-A) In Advanced Gallbladder Cancer Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular mechanisms involved in GBC pathogenesis remain poorly understood. The Vascular Endothelial Growth Factor A (VEGF) is a potent proangiogenic agent involved in the carcinogenesis of many human tumors and it is an attractive target for cancer therapy. The aim of this study was characterize VEGF expression in advanced gallbladder cancer and determine it's relationships with clinicopathologic features and utility as a prognostic factor. VEGF expression was examined by immunohistochemistry (IHC) in tissue microarrays containing 224 advanced gallbladder carcinomas and 39 cases of chronic cholecystitis (CC). The advanced GBC were classified as low or high expression to evaluate the association of VEGF expression level with clinical variables. Statistical analysis was performed using univariate analyses with a significance level of P<0.05; survival analysis was performed by the Kaplan- Meier method with the log-rank test. High expression of VEGF was observed in 183 of 224 (81%) tumors and 2 of 39 (5.1%) of chronic cholecystitis (P<0.0001). The VEGF expression had a significant relationship with clinical or pathological features included histological grade and TNM stage (P<0.05). Moreover, 5-year survival analysis indicated that high expression of VEGF is associated with a poor prognosis in patients with advanced gallbladder cancer (P = 0.0116). Our results indicate that VEGF is highly expressed in gallbladder cancer and correlates with poor prognostic, suggesting that VEGF expression could be used as a biomarker for predicting malignant behavior and to identify a subset of patients who may benefit from anti-VEGF therapies. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"pbk topk differential diagnosis cholangiocarcinoma hepatocellular carcinoma involvement prognosis human cholangiocarcinoma increased expression pdz binding kinase lymphokine activated killer cell originated protein kinase pbk topk associated human malignant tumors study analyzed pbk topk expression hepatic primary tumor explored role cholangiocarcinoma biology seventy four cholangiocarcinomas 33 hepatocellular carcinomas 10 normal liver tissues prepared paraffin embedded specimens pbk topk protein assessed immunohistochemical staining survival time analyzed kaplan meier method protein mrna pbk topk cell cycle cholangiocarcinoma cell line pbk topk suppression small interfere rna studied western blot semiquantitative reverse transcriptase polymerase chain reaction flow cytometry respectively pbk topk usually expressed normal bile duct epithelial cells much frequently expressed cholangiocarcinoma 68 74 never expressed hepatocytes hepatocellular carcinomas 0 33 pbk topk regulation related poor prognosis patients cholangiocarcinoma p 013 epidermal growth factor enhance pbk topk expression cholangiocarcinoma qbc 939 cells suppression pbk topk cells affect proliferation pbk topk protein serve useful indicator histopathologic differentiation cholangiocarcinoma hepatocellular carcinomas low expression pbk topk predicative poor survival cholangiocarcinoma patients stn","probabilities":0.9467213,"Title":"Pbk/Topk In The Differential Diagnosis Of Cholangiocarcinoma From Hepatocellular Carcinoma And Its Involvement In Prognosis Of Human Cholangiocarcinoma","Abstract":"The increased expression of PDZ binding kinase/lymphokine-activated killer T-cell-originated protein kinase (PBK/TOPK) is associated with some human malignant tumors. In this study, we analyzed PBK/TOPK expression in hepatic primary tumor and explored its role in cholangiocarcinoma biology. Seventy-four cholangiocarcinomas, 33 hepatocellular carcinomas, and 10 normal liver tissues were prepared from paraffin-embedded specimens. PBK/TOPK protein was assessed by immunohistochemical staining, and the survival time was analyzed with the Kaplan-Meier method. The protein, mRNA of PBK/TOPK, and cell cycle of cholangiocarcinoma cell line after PBK/TOPK suppression with small interfere RNA were studied by Western blot, semiquantitative reverse transcriptase-polymerase chain reaction, and flow cytometry, respectively. PBK/TOPK was usually expressed in normal bile duct epithelial cells and much more frequently expressed in cholangiocarcinoma (68/74) but never expressed in hepatocytes and hepatocellular carcinomas (0/33). PBK/TOPK down-regulation was related to the poor prognosis of patients with cholangiocarcinoma (P = .013). Epidermal growth factor can enhance PBK/TOPK expression in cholangiocarcinoma QBC 939 cells, but suppression of PBK/TOPK in the cells did not affect their proliferation. PBK/TOPK protein could serve as a useful indicator for histopathologic differentiation between cholangiocarcinoma and hepatocellular carcinomas and the low expression of PBK/TOPK is predicative of poor survival in cholangiocarcinoma patients.","Source":"STN","category":"HUMAN","training_data":"Pbk/Topk In The Differential Diagnosis Of Cholangiocarcinoma From Hepatocellular Carcinoma And Its Involvement In Prognosis Of Human Cholangiocarcinoma The increased expression of PDZ binding kinase/lymphokine-activated killer T-cell-originated protein kinase (PBK/TOPK) is associated with some human malignant tumors. In this study, we analyzed PBK/TOPK expression in hepatic primary tumor and explored its role in cholangiocarcinoma biology. Seventy-four cholangiocarcinomas, 33 hepatocellular carcinomas, and 10 normal liver tissues were prepared from paraffin-embedded specimens. PBK/TOPK protein was assessed by immunohistochemical staining, and the survival time was analyzed with the Kaplan-Meier method. The protein, mRNA of PBK/TOPK, and cell cycle of cholangiocarcinoma cell line after PBK/TOPK suppression with small interfere RNA were studied by Western blot, semiquantitative reverse transcriptase-polymerase chain reaction, and flow cytometry, respectively. PBK/TOPK was usually expressed in normal bile duct epithelial cells and much more frequently expressed in cholangiocarcinoma (68/74) but never expressed in hepatocytes and hepatocellular carcinomas (0/33). PBK/TOPK down-regulation was related to the poor prognosis of patients with cholangiocarcinoma (P = .013). Epidermal growth factor can enhance PBK/TOPK expression in cholangiocarcinoma QBC 939 cells, but suppression of PBK/TOPK in the cells did not affect their proliferation. PBK/TOPK protein could serve as a useful indicator for histopathologic differentiation between cholangiocarcinoma and hepatocellular carcinomas and the low expression of PBK/TOPK is predicative of poor survival in cholangiocarcinoma patients. STN","prediction_labels":"ANIMAL"},{"cleaned":"impact liver resection survival locally advanced intrahepatic cholangiocarcinoma tumors propensity score analysis background aim work investigate prognostic impact liver resection lr locally advanced intrahepatic cholangiocarcinoma ic comparison alternative palliative chemotherapy ctx method retrospective cohort study performed utilizing surveillance epidemiology end results seer database identify locally advanced ic patients based american joint committee cancer ajcc staging system locally advanced ic defined stage iii iva 7th edition 7th ed stage iii 8th edition 8th ed study population sub classified lr group propensity score ps matched ctx group results 7th ed module median survival lr group n 154 35 months 3 year survival rate 40 8 ps matched ctx group n 154 median survival 14 months 3 year survival rate 5 5 p 0 007 survival rates superior lr group ps matched ctx group 8th ed module well worse prognosis reported lr patients 65 years old hr 2 618 p 001 multifocal lesions hr 1 890 p 0 025 conclusion hepatic resection associated favorable impact prognosis chemotherapy ic stage iii iva 7th edition stage iiib 8th edition ajcc staging system worse outcome observed lr patients 65 years multifocal lesions randomized control studies recommended confirm role surgical resection management advanced cases ic clarify related prognostic factors stn","probabilities":0.9799733,"Title":"The Impact Of Liver Resection On Survival For Locally Advanced Intrahepatic Cholangiocarcinoma Tumors: A Propensity Score Analysis","Abstract":"Background: Aim of work was to investigate the prognostic impact of liver resection (LR) on locally advanced Intrahepatic Cholangiocarcinoma (IC) in comparison to alternative palliative chemotherapy (CTx). \r\n\r\n Method: A retrospective cohort study performed utilizing Surveillance, Epidemiology, and End Results (SEER) database to identify Locally advanced IC patients. Based on the American Joint Committee on Cancer (AJCC) Staging System, locally advanced IC was defined as: Stage III and IVa - 7th edition (7th-ed) or stage III - 8th edition (8th-ed). Study population were sub-classified into: LR group and a propensity score (PS) matched CTx group. \r\n\r\n Results: In 7th-ed module, the median survival for LR group (n = 154) was 35 months, and the 3-year survival rate was 40.8%. In PS matched CTx group (n = 154); the median survival was 14 months and the 3-year survival rate was 5.5% (P = 0.007). Survival rates were superior for LR group over PS matched CTx group in 8th-ed module as well. Worse prognosis has been reported in LR patients above 65 years old (HR 2.618, P = 001) and in multifocal lesions (HR 1.890, P = 0.025). \r\n\r\n Conclusion: Hepatic resection was associated with a favorable impact on prognosis over chemotherapy for IC stage III and IVa of the 7th edition and for stage IIIb of 8th edition of AJCC staging system. Worse outcome has been observed in LR patients >65 years and with multifocal lesions. Randomized control studies are recommended to confirm the role of surgical resection in the management for advanced cases of IC, and to clarify the related prognostic factors.","Source":"STN","category":"HUMAN","training_data":"The Impact Of Liver Resection On Survival For Locally Advanced Intrahepatic Cholangiocarcinoma Tumors: A Propensity Score Analysis Background: Aim of work was to investigate the prognostic impact of liver resection (LR) on locally advanced Intrahepatic Cholangiocarcinoma (IC) in comparison to alternative palliative chemotherapy (CTx). \r\n\r\n Method: A retrospective cohort study performed utilizing Surveillance, Epidemiology, and End Results (SEER) database to identify Locally advanced IC patients. Based on the American Joint Committee on Cancer (AJCC) Staging System, locally advanced IC was defined as: Stage III and IVa - 7th edition (7th-ed) or stage III - 8th edition (8th-ed). Study population were sub-classified into: LR group and a propensity score (PS) matched CTx group. \r\n\r\n Results: In 7th-ed module, the median survival for LR group (n = 154) was 35 months, and the 3-year survival rate was 40.8%. In PS matched CTx group (n = 154); the median survival was 14 months and the 3-year survival rate was 5.5% (P = 0.007). Survival rates were superior for LR group over PS matched CTx group in 8th-ed module as well. Worse prognosis has been reported in LR patients above 65 years old (HR 2.618, P = 001) and in multifocal lesions (HR 1.890, P = 0.025). \r\n\r\n Conclusion: Hepatic resection was associated with a favorable impact on prognosis over chemotherapy for IC stage III and IVa of the 7th edition and for stage IIIb of 8th edition of AJCC staging system. Worse outcome has been observed in LR patients >65 years and with multifocal lesions. Randomized control studies are recommended to confirm the role of surgical resection in the management for advanced cases of IC, and to clarify the related prognostic factors. STN","prediction_labels":"HUMAN"},{"cleaned":"detection circulating tumor cells peripheral blood independently predict survival patients advance malignant biliary tract diseases new guide selection stents abstract available google scholar","probabilities":0.9799733,"Title":"Detection Of Circulating Tumor Cells In The Peripheral Blood Independently Predict Survival In Patients With Advance Malignant Biliary Tract Diseases: A New Guide For Selection Of Stents","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Detection Of Circulating Tumor Cells In The Peripheral Blood Independently Predict Survival In Patients With Advance Malignant Biliary Tract Diseases: A New Guide For Selection Of Stents Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"high throughput molecular profiling reveals differential mutation patterns intrahepatic cholangiocarcinomas arising chronic advanced liver diseases intrahepatic cholangiocarcinomas occur mostly normal liver also arise chronic advanced liver diseases however genetic differences two groups yet examined high throughput mass spectrometry based platform used interrogate mutations intrahepatic cholangiocarcinomas compare mutation profiles 43 intrahepatic cholangiocarcinomas normal liver 38 chronic advanced liver diseases forty seven mutations 11 genes identified 38 81 cases 46 9 commonly mutated gene kras 11 81 13 6 followed mlh1 7 81 8 6 nras 7 81 8 6 gnas 6 81 7 4 egfr 6 81 7 4 braf apc pik3ca cdkn2a pten tp53 mutations found less 5 overall mutation rate intrahepatic cholangiocarcinomas chronic advanced liver disease 15 38 39 5 95 confidence interval 23 9 55 0 lower intrahepatic cholangiocarcinomas normal liver 23 43 53 5 95 confidence interval 38 5 68 3 intrahepatic cholangiocarcinomas chronic advanced liver disease showed higher egfr mutation rate 5 38 13 2 vs 1 43 2 3 lower mutation rates kras 3 38 7 9 vs 8 43 18 6 mlh1 2 38 5 3 vs 5 43 11 6 gnas 1 38 2 6 vs 5 43 11 6 compared intrahepatic cholangiocarcinomas normal liver mutations pik3ca pten cdkn2a tp53 harbored intrahepatic cholangiocarcinomas normal liver kras p 0 0075 gnas mutations p 0 0256 associated poor overall survival patients intrahepatic cholangiocarcinoma differential mutation patterns intrahepatic cholangiocarcinomas chronic advanced liver disease suggest different cholangiocarcinogenesis depending upon predisposing factors support different strategy targeted therapy applied intrahepatic cholangiocarcinoma subtypes stn","probabilities":0.9799733,"Title":"High Throughput Molecular Profiling Reveals Differential Mutation Patterns In Intrahepatic Cholangiocarcinomas Arising In Chronic Advanced Liver Diseases","Abstract":"Intrahepatic cholangiocarcinomas occur mostly in the normal liver but they also arise in chronic advanced liver diseases. However, genetic differences between two groups have yet to be examined. High throughput mass spectrometry-based platform was used to interrogate mutations in intrahepatic cholangiocarcinomas and to compare the mutation profiles between 43 intrahepatic cholangiocarcinomas with normal liver and 38 with chronic advanced liver diseases. Forty seven mutations in 11 genes were identified in 38 of 81 cases (46.9%). The most commonly mutated gene was KRAS (11/81, 13.6%), followed by MLH1 (7/81, 8.6%), NRAS (7/81, 8.6%), GNAS (6/81, 7.4%), and EGFR (6/81, 7.4%). BRAF, APC, PIK3CA, CDKN2A, PTEN, and TP53 mutations were found with less than 5%. Overall mutation rate of intrahepatic cholangiocarcinomas with chronic advanced liver disease (15/38, 39.5%, 95% confidence interval: 23.9-55.0) was lower than that of intrahepatic cholangiocarcinomas with normal liver (23/43, 53.5%, 95% confidence interval: 38.5-68.3). Intrahepatic cholangiocarcinomas with chronic advanced liver disease showed higher EGFR mutation rate (5/38, 13.2% vs 1/43, 2.3%) and lower mutation rates of KRAS (3/38, 7.9% vs 8/43, 18.6%), MLH1 (2/38, 5.3% vs 5/43, 11.6%), and GNAS (1/38, 2.6% vs 5/43, 11.6%), compared with those in intrahepatic cholangiocarcinomas with normal liver. Mutations in PIK3CA, PTEN, CDKN2A, and TP53 were harbored only in intrahepatic cholangiocarcinomas with normal liver. KRAS (P=0.0075) or GNAS mutations (P=0.0256) were associated with poor overall survival in all patients with intrahepatic cholangiocarcinoma. Differential mutation patterns of intrahepatic cholangiocarcinomas with chronic advanced liver disease suggest different cholangiocarcinogenesis depending upon the predisposing factors, and support that different strategy for targeted therapy should be applied in intrahepatic cholangiocarcinoma subtypes.","Source":"STN","category":"ANIMAL","training_data":"High Throughput Molecular Profiling Reveals Differential Mutation Patterns In Intrahepatic Cholangiocarcinomas Arising In Chronic Advanced Liver Diseases Intrahepatic cholangiocarcinomas occur mostly in the normal liver but they also arise in chronic advanced liver diseases. However, genetic differences between two groups have yet to be examined. High throughput mass spectrometry-based platform was used to interrogate mutations in intrahepatic cholangiocarcinomas and to compare the mutation profiles between 43 intrahepatic cholangiocarcinomas with normal liver and 38 with chronic advanced liver diseases. Forty seven mutations in 11 genes were identified in 38 of 81 cases (46.9%). The most commonly mutated gene was KRAS (11/81, 13.6%), followed by MLH1 (7/81, 8.6%), NRAS (7/81, 8.6%), GNAS (6/81, 7.4%), and EGFR (6/81, 7.4%). BRAF, APC, PIK3CA, CDKN2A, PTEN, and TP53 mutations were found with less than 5%. Overall mutation rate of intrahepatic cholangiocarcinomas with chronic advanced liver disease (15/38, 39.5%, 95% confidence interval: 23.9-55.0) was lower than that of intrahepatic cholangiocarcinomas with normal liver (23/43, 53.5%, 95% confidence interval: 38.5-68.3). Intrahepatic cholangiocarcinomas with chronic advanced liver disease showed higher EGFR mutation rate (5/38, 13.2% vs 1/43, 2.3%) and lower mutation rates of KRAS (3/38, 7.9% vs 8/43, 18.6%), MLH1 (2/38, 5.3% vs 5/43, 11.6%), and GNAS (1/38, 2.6% vs 5/43, 11.6%), compared with those in intrahepatic cholangiocarcinomas with normal liver. Mutations in PIK3CA, PTEN, CDKN2A, and TP53 were harbored only in intrahepatic cholangiocarcinomas with normal liver. KRAS (P=0.0075) or GNAS mutations (P=0.0256) were associated with poor overall survival in all patients with intrahepatic cholangiocarcinoma. Differential mutation patterns of intrahepatic cholangiocarcinomas with chronic advanced liver disease suggest different cholangiocarcinogenesis depending upon the predisposing factors, and support that different strategy for targeted therapy should be applied in intrahepatic cholangiocarcinoma subtypes. STN","prediction_labels":"HUMAN"},{"cleaned":"impact salinomycin human cholangiocarcinoma induction apoptosis impairment tumor cell proliferation vitro background cholangiocarcinoma cc primary liver cancer increasing incidence worldwide despite efforts made past years prognosis remains poor least part might explained pronounced resistance cc cells undergo apoptosis thus new therapeutic strategies imperatively required study investigated effect salinomycin polyether ionophore antibiotic cc cells appropriate agent treat cc salinomycin quite recently identified induce apoptosis cancer stem cells overcome apoptosis resistance several leukemia cells cancer cell lines different origin methods delineate effects salinomycin cc established vitro cell culture model using three different human cc cell lines treatment apoptosis well migration proliferation behavior assessed additional cell cycle analyses performed flowcytometry results demonstrating annexin v tunel positivity human cc cells provide evidence salinomycin reveals capacity break apoptosis resistance cc cells furthermore able demonstrate non apoptotic cell fraction characterized sustainable impaired migration proliferation cell cycle analyses revealed g2 phase accumulation human cc cells treatment salinomycin even though apoptosis induced two three cell lines cc cells one cell line remained unaffected regard apoptosis revealed cc cells decreased proliferation migration conclusion study able demonstrate salinomycin effective agent previously resistant cc cells might potential candidate treatment cc future stn","probabilities":0.9467213,"Title":"Impact Of Salinomycin On Human Cholangiocarcinoma: Induction Of Apoptosis And Impairment Of Tumor Cell Proliferation In Vitro","Abstract":"Background: Cholangiocarcinoma (CC) is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin. \r\n\r\n Methods: To delineate the effects of Salinomycin on CC, we established an in vitro cell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry. \r\n\r\n Results: By demonstrating Annexin V and TUNEL positivity of human CC cells, we provide evidence that Salinomycin reveals the capacity to break apoptosis-resistance in CC cells. Furthermore, we are able to demonstrate that the non-apoptotic cell fraction is characterized by sustainable impaired migration and proliferation. Cell cycle analyses revealed G2-phase accumulation of human CC cells after treatment with Salinomycin. Even though apoptosis is induced in two of three cell lines of CC cells, one cell line remained unaffected in regard of apoptosis but revealed as the other CC cells decreased proliferation and migration. \r\n\r\n Conclusion: In this study, we are able to demonstrate that Salinomycin is an effective agent against previously resistant CC cells and might be a potential candidate for the treatment of CC in the future.","Source":"STN","category":"ANIMAL","training_data":"Impact Of Salinomycin On Human Cholangiocarcinoma: Induction Of Apoptosis And Impairment Of Tumor Cell Proliferation In Vitro Background: Cholangiocarcinoma (CC) is a primary liver cancer with increasing incidence worldwide. Despite all efforts made in past years, prognosis remains to be poor. At least in part, this might be explained by a pronounced resistance of CC cells to undergo apoptosis. Thus, new therapeutic strategies are imperatively required. In this study we investigated the effect of Salinomycin, a polyether ionophore antibiotic, on CC cells as an appropriate agent to treat CC. Salinomycin was quite recently identified to induce apoptosis in cancer stem cells and to overcome apoptosis-resistance in several leukemia-cells and other cancer cell lines of different origin. \r\n\r\n Methods: To delineate the effects of Salinomycin on CC, we established an in vitro cell culture model using three different human CC cell lines. After treatment apoptosis as well as migration and proliferation behavior was assessed and additional cell cycle analyses were performed by flowcytometry. \r\n\r\n Results: By demonstrating Annexin V and TUNEL positivity of human CC cells, we provide evidence that Salinomycin reveals the capacity to break apoptosis-resistance in CC cells. Furthermore, we are able to demonstrate that the non-apoptotic cell fraction is characterized by sustainable impaired migration and proliferation. Cell cycle analyses revealed G2-phase accumulation of human CC cells after treatment with Salinomycin. Even though apoptosis is induced in two of three cell lines of CC cells, one cell line remained unaffected in regard of apoptosis but revealed as the other CC cells decreased proliferation and migration. \r\n\r\n Conclusion: In this study, we are able to demonstrate that Salinomycin is an effective agent against previously resistant CC cells and might be a potential candidate for the treatment of CC in the future. STN","prediction_labels":"ANIMAL"},{"cleaned":"contemporary management perihilar cholangiocarcinoma nontransplant hepatopancreatobiliary center background perihilar cholangiocarcinoma phcc rare tumor poor prognosis outcomes may optimized centralization recent trends suggest improvement localization transplant centers study examines outcomes management phcc nontransplant hepatopancreatobiliary center methods data collected prospectively patients undergoing treatment phcc october 1999 may 2011 twenty four patients underwent surgery 54 patients inoperable phcc outcome data reported results twenty two 24 patients required liver resection histological r0 status 12 50 hospital mortality occurred two 8 mean survival patients undergoing resection 39 95 ci 16 61 months mean survival nonresected patients 5 95 ci 3 7 months p 0 0001 log rank mantel cox test conclusion currently acceptable standards holistic care patients phcc provided nontransplant regional hepatopancreatobiliary center centralization may improve resection volumes allow patients benefit extended liver resection techniques pubmed","probabilities":0.9799733,"Title":"Contemporary management of perihilar cholangiocarcinoma in a nontransplant hepatopancreatobiliary center","Abstract":"BACKGROUND: Perihilar cholangiocarcinoma (PHCC) is a rare tumor with a poor prognosis. Outcomes may be optimized by centralization. Recent trends suggest further improvement by localization to transplant centers. This study examines outcomes from the management of PHCC in a nontransplant hepatopancreatobiliary center. METHODS: Data were collected prospectively from patients undergoing treatment for PHCC from October 1999 to May 2011. Twenty-four patients underwent surgery. A further 54 patients had inoperable PHCC. Outcome data are reported. RESULTS: Twenty-two of 24 patients required liver resection with histological R0 status in 12 (50%). In-hospital mortality occurred in two (8%). The mean survival of patients undergoing resection was 39 (95% CI: 16-61) months. The mean survival of nonresected patients was 5 (95% CI: 3-7) months (P<0.0001; log-rank; Mantel-Cox test). CONCLUSION: Currently acceptable standards of holistic care for patients with PHCC can be provided in a nontransplant regional hepatopancreatobiliary center. Further centralization may improve resection volumes and allow more patients to benefit from extended liver resection techniques.","Source":"PubMed","category":"HUMAN","training_data":"Contemporary management of perihilar cholangiocarcinoma in a nontransplant hepatopancreatobiliary center BACKGROUND: Perihilar cholangiocarcinoma (PHCC) is a rare tumor with a poor prognosis. Outcomes may be optimized by centralization. Recent trends suggest further improvement by localization to transplant centers. This study examines outcomes from the management of PHCC in a nontransplant hepatopancreatobiliary center. METHODS: Data were collected prospectively from patients undergoing treatment for PHCC from October 1999 to May 2011. Twenty-four patients underwent surgery. A further 54 patients had inoperable PHCC. Outcome data are reported. RESULTS: Twenty-two of 24 patients required liver resection with histological R0 status in 12 (50%). In-hospital mortality occurred in two (8%). The mean survival of patients undergoing resection was 39 (95% CI: 16-61) months. The mean survival of nonresected patients was 5 (95% CI: 3-7) months (P<0.0001; log-rank; Mantel-Cox test). CONCLUSION: Currently acceptable standards of holistic care for patients with PHCC can be provided in a nontransplant regional hepatopancreatobiliary center. Further centralization may improve resection volumes and allow more patients to benefit from extended liver resection techniques. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumor suppressor role mir 107 mir 326 peri ampullary carcinoma association metabolic reprogramming cells introduction peri ampullarycarcinomaisoneofthemostprevalentpancreaticmalignancies world due lack effective therapies ever increasing resistance drugs new approaches effective treatment warranted various factors regulate drug resistance cancer cells metabolism known play one important roles carcinogenesis itisalsoevidentthatthephenomenonofmetabolicreprogrammingpromotes tumor progression study designed check role mirnas metabolic reprogramming peri ampullary carcinoma methodology two mirnas mir 107 mir 325wereselectedonthebasisofexistingliteratureandtheirroleinmetabolicreprogramming different cancers expression mirnas target genes pyruvate kinase m2 pkm2 lactate dehydrogenase ldh glutaminase gls1 analyzed 30 peri ampullary carcinoma surgical tissue samples along healthy controls qpcr also circulating levels mir 107 mir 326 assessed q pcr corresponding blood samples tissues compared circulating levels 35 healthy controls mir 107 mir 326were transfected individually combination pancreatic cancer cell line miapaca effect cell proliferation cell survival mtt assay monitored alteration metabolic response measured glucose uptake lactate production glutamine production assay results significantly decreased expression mir 107 mir326 found tissue blood samples patients compared healthy controls also pkm2 ldh gls1 highly expressed tumor tissues compared adjacent normal tissue vitro transfection mir107 mir 326 co transfection mir 107 mir 326 significantly decreased expressionofmetabolic genes pkm2 ldh andgls1 simultaneously theglucoseuptake lactateproduction andglutamateproductionsignificantlydecreasedincellstransfectedwith individualmir 107and326andinco transfection thetransfectionresultsalsodemonstrated decreased cell proliferation survival conclusion results indicate role mir 107 326 tumor suppressor mirna pancreatic cancer enhancing sensitivityofcelltowardsthetreatment hence mir 107and326mayprovetobeapromising target designing novel therapeutic approach treatment pancreatic cancer google scholar","probabilities":0.9467213,"Title":"Tumor Suppressor Role Of Mir-107 And Mir-326 In Peri-Ampullary Carcinoma In Association With Metabolic Reprogramming Of Cells","Abstract":"Introduction:Peri-ampullarycarcinomaisoneofthemostprevalentpancreaticmalignancies in the world. Due to the lack of effective therapies, ever-increasing resistance against drugs, new approaches to effective treatment are warranted. Various factors regulate the drug resistance in cancer cells and metabolism is known to play one of the important roles in carcinogenesis.Itisalsoevidentthatthephenomenonofmetabolicreprogrammingpromotes tumor progression. So this study was designed to check the role of miRNAs in metabolic reprogramming in peri-ampullary carcinoma. Methodology: Two miRNAs; miR-107 and miR-325wereselectedonthebasisofexistingliteratureandtheirroleinmetabolicreprogramming in different cancers. The expression of these miRNAs and their target genes Pyruvate kinase M2 (PKM2), Lactate dehydrogenase (LDH) and Glutaminase (GLS1) were analyzed in 30 peri-ampullary carcinoma surgical tissue samples along with healthy controls by qPCR. Also, the circulating levels of miR-107 and miR-326 were assessed by q-PCR in corresponding blood samples (of above tissues) and were compared with circulating levels in 35 healthy controls. miR-107 and miR-326were transfected individually and in combination in a pancreatic cancer cell line (MiaPaCa) and its effect on cell proliferation and cell survival (by MTT assay) was monitored. Alteration in metabolic response was measured by glucose uptake, lactate production, and glutamine production assay. Results: Significantly decreased expression of miR-107 and miR326 was found in both tissue and blood samples from patients compared to healthy controls. Also, PKM2, LDH, and GLS1 were highly expressed in tumor tissues compared to adjacent normal tissue. In-vitro transfection of miR107 and mir-326 and co-transfection of mir-107 and mir-326 significantly decreased the expressionofmetabolic genes(PKM2,LDH,andGLS1). Simultaneously,theglucoseuptake, lactateproduction,andglutamateproductionsignificantlydecreasedincellstransfectedwith individualmiR-107and326andinco-transfection.Thetransfectionresultsalsodemonstrated decreased cell proliferation and survival. Conclusion: Our results indicate the role of miR 107 and 326 as the tumor suppressor and miRNA in pancreatic cancer by enhancing the sensitivityofcelltowardsthetreatment.Hence,mir-107and326mayprovetobeapromising target designing a novel therapeutic approach for the treatment of pancreatic cancer.","Source":"Google Scholar","category":"ANIMAL","training_data":"Tumor Suppressor Role Of Mir-107 And Mir-326 In Peri-Ampullary Carcinoma In Association With Metabolic Reprogramming Of Cells Introduction:Peri-ampullarycarcinomaisoneofthemostprevalentpancreaticmalignancies in the world. Due to the lack of effective therapies, ever-increasing resistance against drugs, new approaches to effective treatment are warranted. Various factors regulate the drug resistance in cancer cells and metabolism is known to play one of the important roles in carcinogenesis.Itisalsoevidentthatthephenomenonofmetabolicreprogrammingpromotes tumor progression. So this study was designed to check the role of miRNAs in metabolic reprogramming in peri-ampullary carcinoma. Methodology: Two miRNAs; miR-107 and miR-325wereselectedonthebasisofexistingliteratureandtheirroleinmetabolicreprogramming in different cancers. The expression of these miRNAs and their target genes Pyruvate kinase M2 (PKM2), Lactate dehydrogenase (LDH) and Glutaminase (GLS1) were analyzed in 30 peri-ampullary carcinoma surgical tissue samples along with healthy controls by qPCR. Also, the circulating levels of miR-107 and miR-326 were assessed by q-PCR in corresponding blood samples (of above tissues) and were compared with circulating levels in 35 healthy controls. miR-107 and miR-326were transfected individually and in combination in a pancreatic cancer cell line (MiaPaCa) and its effect on cell proliferation and cell survival (by MTT assay) was monitored. Alteration in metabolic response was measured by glucose uptake, lactate production, and glutamine production assay. Results: Significantly decreased expression of miR-107 and miR326 was found in both tissue and blood samples from patients compared to healthy controls. Also, PKM2, LDH, and GLS1 were highly expressed in tumor tissues compared to adjacent normal tissue. In-vitro transfection of miR107 and mir-326 and co-transfection of mir-107 and mir-326 significantly decreased the expressionofmetabolic genes(PKM2,LDH,andGLS1). Simultaneously,theglucoseuptake, lactateproduction,andglutamateproductionsignificantlydecreasedincellstransfectedwith individualmiR-107and326andinco-transfection.Thetransfectionresultsalsodemonstrated decreased cell proliferation and survival. Conclusion: Our results indicate the role of miR 107 and 326 as the tumor suppressor and miRNA in pancreatic cancer by enhancing the sensitivityofcelltowardsthetreatment.Hence,mir-107and326mayprovetobeapromising target designing a novel therapeutic approach for the treatment of pancreatic cancer. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"gallbladder cancer improvement survival time swedish population background gallbladder cancer gbc extremely poor outcome aim study examine trends gbc incidence treatment overall survival complete population affected persons well defined region sweden 2000 2014 material methods altogether 546 individuals gbc identified sweden regional cancer centre west subjects grouped three 5 year periods period 2000 2004 period b 2005 2009 period c 2010 2014 survival diagnosis staging grading treatment period investigated patients dead date diagnosis n 39 patients invasive cancer n 25 included analysis results incidence unchanged study period survival curves time periods significantly separated median survival 4 7 months period 4 8 months period b 6 1 months period c stage migration m1 periods b c occurred survival improved cohorts individuals diagnosed using diagnostic imaging p 02 177 curatively aiming operative procedures carried 482 persons 37 survival surgery three periods improved time p 02 individuals underwent liver bed resection cholecystectomy better survival individuals cholecystectomy combined liver resection persons treated chemotherapy significant impact found survival total gbc population conclusions although signs improved diagnosis gbc survival rate improve time significant stage migration m1 periods b c therapeutics able downsize cancer increase effectiveness surgery curative intent warranted stn","probabilities":0.9799733,"Title":"Gallbladder Cancer - No Improvement In Survival Over Time In A Swedish Population","Abstract":"Background: Gallbladder cancer (GBC) has an extremely poor outcome. The aim of this study was to examine trends in GBC incidence, treatment and overall survival in a complete population of affected persons in a well-defined region in Sweden in 2000-2014. \r\n\r\n Material and methods: Altogether 546 individuals with GBC were identified at Sweden's Regional Cancer Centre West. Subjects were grouped into three 5-year periods (Period A: 2000-2004, Period B: 2005-2009 and Period C: 2010-2014) and the survival, diagnosis, staging, grading and treatment for each period were investigated. Patients dead at date of diagnosis (n = 39) and patients with not invasive cancer (n = 25) were not included in the analysis. \r\n\r\n Results: The incidence was unchanged over the study period. The survival curves for the time periods were not significantly separated. Median survival was 4.7 months in Period A, 4.8 months in Period B and 6.1 months in Period C. Stage migration to more M1 in Periods B and C occurred and survival was improved for these cohorts. More individuals were diagnosed using only diagnostic imaging (p = .02). There were 177 curatively aiming operative procedures carried out on 482 persons (37%). The survival after surgery for the three periods improved over time (p = .02). Individuals who underwent a liver bed resection after a cholecystectomy had better survival than individuals who had cholecystectomy combined with liver resection. More persons were treated with chemotherapy, but no significant impact was found on survival in the total GBC population. \r\n\r\n Conclusions: Although there were signs of improved diagnosis of GBC, the survival rate did not improve over time. There was a significant stage migration to more M1 in Periods B and C. Therapeutics able to downsize a cancer and increase the effectiveness of surgery with curative intent are warranted.","Source":"STN","category":"HUMAN","training_data":"Gallbladder Cancer - No Improvement In Survival Over Time In A Swedish Population Background: Gallbladder cancer (GBC) has an extremely poor outcome. The aim of this study was to examine trends in GBC incidence, treatment and overall survival in a complete population of affected persons in a well-defined region in Sweden in 2000-2014. \r\n\r\n Material and methods: Altogether 546 individuals with GBC were identified at Sweden's Regional Cancer Centre West. Subjects were grouped into three 5-year periods (Period A: 2000-2004, Period B: 2005-2009 and Period C: 2010-2014) and the survival, diagnosis, staging, grading and treatment for each period were investigated. Patients dead at date of diagnosis (n = 39) and patients with not invasive cancer (n = 25) were not included in the analysis. \r\n\r\n Results: The incidence was unchanged over the study period. The survival curves for the time periods were not significantly separated. Median survival was 4.7 months in Period A, 4.8 months in Period B and 6.1 months in Period C. Stage migration to more M1 in Periods B and C occurred and survival was improved for these cohorts. More individuals were diagnosed using only diagnostic imaging (p = .02). There were 177 curatively aiming operative procedures carried out on 482 persons (37%). The survival after surgery for the three periods improved over time (p = .02). Individuals who underwent a liver bed resection after a cholecystectomy had better survival than individuals who had cholecystectomy combined with liver resection. More persons were treated with chemotherapy, but no significant impact was found on survival in the total GBC population. \r\n\r\n Conclusions: Although there were signs of improved diagnosis of GBC, the survival rate did not improve over time. There was a significant stage migration to more M1 in Periods B and C. Therapeutics able to downsize a cancer and increase the effectiveness of surgery with curative intent are warranted. STN","prediction_labels":"HUMAN"},{"cleaned":"14 3 3 apkc synergistically facilitate epithelial mesenchymal transition cholangiocarcinoma via gsk 3 snail signaling pathway cholangiocarcinoma cca invasion metastasis primary causes poor survival rates patients epithelial mesenchymal transition emt crucial step cancer invasion metastasis however still unclear molecular mechanism study expression 14 3 3 atypical protein kinase c apkc detected cca tissues cell lines meanwhile established emt model cca cells investigated 14 3 3 apkc co regulatory effect emt vitro vivo identified downstream molecular glycogen synthase kinase 3 beta gsk 3 snail signalling pathway contribute regulating emt data showed expression 14 3 3 apkc synergistically increased cca tissues compared adjacent noncancerous tissues intimately associated differentiation tumour node metastasis tnm stage multivariate cox regression analysis indicated high 14 3 3 apkc expression separately predicted poor prognosis independent prognostic indicators patients cca co ip experiment confirmed mutual binding relationship 14 3 3 apkc small interfering rnas sirna rescue experiment demonstrated 14 3 3 apkc regulated addition 14 3 3 apkc pretreatment si rna inhibit phosphorylated gsk 3 snail expression emt meanwhile silence 14 3 3 apkc suppressed cca cells migration metastasis proliferation vitro vivo study demonstrates 14 3 3 apkc synergistically facilitate emt cca via gsk 3 snail signalling pathway may potential therapeutic target cca stn","probabilities":0.9467213,"Title":"14-3-3? And Apkc-? Synergistically Facilitate Epithelial-Mesenchymal Transition Of Cholangiocarcinoma Via Gsk-3ß/Snail Signaling Pathway","Abstract":"Cholangiocarcinoma (CCA) invasion and metastasis are the primary causes of poor survival rates in patients. The epithelial-mesenchymal transition (EMT) is a crucial step in cancer invasion and metastasis. However, it is still unclear of the molecular mechanism. In this study, the expression of 14-3-3ζ and atypical protein kinase C-ι (aPKC-ι) was further detected in CCA tissues and cell lines. Meanwhile, we established the EMT model of CCA cells and investigated 14-3-3ζ and aPKC-ι co-regulatory effect on the EMT in vitro and in vivo. Further, we identified the downstream molecular glycogen synthase kinase 3 beta (GSK-3β)/Snail signalling pathway that contribute to regulating the EMT. Our data showed that the expression of 14-3-3ζ and aPKC-ι was synergistically increased in CCA tissues compared with adjacent noncancerous tissues and was intimately associated with differentiation and the tumour-node-metastasis (TNM) stage. Multivariate Cox regression analysis indicated that high 14-3-3ζ and aPKC-ι expression separately predicted a poor prognosis and were independent prognostic indicators in patients with CCA. The CO-IP experiment confirmed that the mutual binding relationship between 14-3-3ζ and aPKC-ι. Small interfering RNAs and siRNA rescue experiment demonstrated that 14-3-3ζ and aPKC-ι regulated each other. In addition, 14-3-3ζ and aPKC-ι pretreatment by si-RNA inhibit the phosphorylated GSK-3β and Snail expression during EMT. Meanwhile, silence of 14-3-3ζ or aPKC-ι suppressed CCA cells migration, metastasis and proliferation in vitro and in vivo. Our study demonstrates that 14-3-3ζ and aPKC-ι synergistically facilitate EMT of CCA via GSK-3β/Snail signalling pathway, and may be potential therapeutic target for CCA.","Source":"STN","category":"ANIMAL","training_data":"14-3-3? And Apkc-? Synergistically Facilitate Epithelial-Mesenchymal Transition Of Cholangiocarcinoma Via Gsk-3ß/Snail Signaling Pathway Cholangiocarcinoma (CCA) invasion and metastasis are the primary causes of poor survival rates in patients. The epithelial-mesenchymal transition (EMT) is a crucial step in cancer invasion and metastasis. However, it is still unclear of the molecular mechanism. In this study, the expression of 14-3-3ζ and atypical protein kinase C-ι (aPKC-ι) was further detected in CCA tissues and cell lines. Meanwhile, we established the EMT model of CCA cells and investigated 14-3-3ζ and aPKC-ι co-regulatory effect on the EMT in vitro and in vivo. Further, we identified the downstream molecular glycogen synthase kinase 3 beta (GSK-3β)/Snail signalling pathway that contribute to regulating the EMT. Our data showed that the expression of 14-3-3ζ and aPKC-ι was synergistically increased in CCA tissues compared with adjacent noncancerous tissues and was intimately associated with differentiation and the tumour-node-metastasis (TNM) stage. Multivariate Cox regression analysis indicated that high 14-3-3ζ and aPKC-ι expression separately predicted a poor prognosis and were independent prognostic indicators in patients with CCA. The CO-IP experiment confirmed that the mutual binding relationship between 14-3-3ζ and aPKC-ι. Small interfering RNAs and siRNA rescue experiment demonstrated that 14-3-3ζ and aPKC-ι regulated each other. In addition, 14-3-3ζ and aPKC-ι pretreatment by si-RNA inhibit the phosphorylated GSK-3β and Snail expression during EMT. Meanwhile, silence of 14-3-3ζ or aPKC-ι suppressed CCA cells migration, metastasis and proliferation in vitro and in vivo. Our study demonstrates that 14-3-3ζ and aPKC-ι synergistically facilitate EMT of CCA via GSK-3β/Snail signalling pathway, and may be potential therapeutic target for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"complications transarterial chemoembolization tace treatment liver tumors introduction transarterial chemoembolization tace considered therapeutic option mostly used hepatocellular carcinoma liver colorectal neuroendocrine melanoma metastases although considered safe procedure tace presents complications acute cholecystitis common procedure related complications include pulmonary embolism hepatic abscess bile duct injury gastric mucosa injury less frequently acute pancreatitis aim study review complications following tace liver tumors methods performed retrospective study including tace procedures performed single center period january 2013 december 2016 results 196 patients liver tumors undergone 322 tace 258 80 male 64 20 female mean patient age 66 5years major complications chemoembolization included decompensation edema ascites 6patients acute cholecystitis 4 acute pancreatitis 3 liver rupture 1 liver abscess 1 renal failure 1 postembolization syndrome appeared 71 20 patients multivariate analysis observed concomitant cardiovascular disease 4 5 95 ci 1 2 17 p 025 risk factor development complications conclusions tace safe effective procedure liver tumor treatment majority complications rare present low incidence mortality pubmed","probabilities":0.9799733,"Title":"Complications of transarterial chemoembolization (TACE) in the treatment of liver tumors","Abstract":"INTRODUCTION: Transarterial chemoembolization (TACE) is considered a therapeutic option. It is mostly used in hepatocellular carcinoma or liver colorectal, neuroendocrine or melanoma metastases. Although it is considered a safe procedure, TACE presents complications, such as acute cholecystitis, which is the most common. Other procedure-related complications include pulmonary embolism, hepatic abscess, bile duct injury, gastric mucosa injury and, less frequently, acute pancreatitis. The aim of this study is to review the complications following TACE for liver tumors. METHODS: We performed a retrospective study including all the TACE procedures performed in a single center during the period between January 2013 and December 2016. RESULTS: Out of the 196 patients with liver tumors who had undergone 322 TACE, 258 (80%) were male and 64 (20%) were female. Mean patient age was 66.5years. Major complications after chemoembolization included: decompensation with edema/ascites (6patients), acute cholecystitis (4), acute pancreatitis (3), liver rupture (1), liver abscess (1) and renal failure (1). Postembolization syndrome appeared in 71 (20%) patients. On multivariate analysis, it was observed that concomitant cardiovascular disease (OR: 4.5; 95%CI: 1.2-17; P=.025) is a risk factor for the development of complications. CONCLUSIONS: TACE is a safe and effective procedure for liver tumor treatment. The majority of the complications are rare and present a low incidence of mortality.","Source":"PubMed","category":"HUMAN","training_data":"Complications of transarterial chemoembolization (TACE) in the treatment of liver tumors INTRODUCTION: Transarterial chemoembolization (TACE) is considered a therapeutic option. It is mostly used in hepatocellular carcinoma or liver colorectal, neuroendocrine or melanoma metastases. Although it is considered a safe procedure, TACE presents complications, such as acute cholecystitis, which is the most common. Other procedure-related complications include pulmonary embolism, hepatic abscess, bile duct injury, gastric mucosa injury and, less frequently, acute pancreatitis. The aim of this study is to review the complications following TACE for liver tumors. METHODS: We performed a retrospective study including all the TACE procedures performed in a single center during the period between January 2013 and December 2016. RESULTS: Out of the 196 patients with liver tumors who had undergone 322 TACE, 258 (80%) were male and 64 (20%) were female. Mean patient age was 66.5years. Major complications after chemoembolization included: decompensation with edema/ascites (6patients), acute cholecystitis (4), acute pancreatitis (3), liver rupture (1), liver abscess (1) and renal failure (1). Postembolization syndrome appeared in 71 (20%) patients. On multivariate analysis, it was observed that concomitant cardiovascular disease (OR: 4.5; 95%CI: 1.2-17; P=.025) is a risk factor for the development of complications. CONCLUSIONS: TACE is a safe and effective procedure for liver tumor treatment. The majority of the complications are rare and present a low incidence of mortality. PubMed","prediction_labels":"HUMAN"},{"cleaned":"efficacy gallbladder cancer predictive risk score based pathological findings propensity score matched analysis background optimal prognostic predictive system gallbladder carcinoma gbc established gallbladder cancer predictive risk score gbrs based pathological findings identifies incidental gbc patients risk recurrence objective aimed validate prognostic ability gbrs gbc patients following curative surgery methods fifty six patients gbc underwent curative surgery 1996 2016 included study univariate multivariate analyses performed determine prognostic factors associated overall recurrence free survival propensity score matched analysis performed results median patient age 71 9 years 39 3 patients males patients underwent curative surgery 33 9 simple cholecystectomy 66 1 advanced procedures hepatectomy 32 1 bile duct reconstruction univariate analysis preoperative carbohydrate antigen 19 9 ca19 9 37 u ml p 0 042 postoperative complications p 0 043 high gbrs p 0 001 prognostic factors worse overall survival multivariate analysis ca19 9 37 u ml p 0 039 p 0 043 respectively high gbrs p 0 001 p 0 010 respectively independent risk factors poor overall recurrence free survival propensity score matched analysis gbrs precisely predicted prognosis patients gbc conclusions gbrs easy novel prognostic predicting score validation revealed good discrimination suggesting clinical utility improve individualized prediction survival patients undergoing resection gbc pubmed","probabilities":0.9799733,"Title":"Efficacy of the Gallbladder Cancer Predictive Risk Score Based on Pathological Findings: A Propensity Score-Matched Analysis","Abstract":"BACKGROUND: The optimal prognostic predictive system for gallbladder carcinoma (GBC) has not been established. The gallbladder cancer predictive risk score (GBRS) based on pathological findings identifies incidental GBC patients at risk of recurrence. OBJECTIVE: We aimed to validate the prognostic ability of the GBRS in all GBC patients following curative surgery. METHODS: Fifty-six patients with GBC who underwent curative surgery between 1996 and 2016 were included in this study. Univariate and multivariate analyses were performed to determine prognostic factors associated with overall and recurrence-free survival, and propensity score-matched analysis was performed. RESULTS: The median patient age was 71.9 years, and 39.3% of patients were males. All patients underwent curative surgery (33.9%, simple cholecystectomy; 66.1%, more advanced procedures, such as hepatectomy; and 32.1%, bile duct reconstruction). On univariate analysis, preoperative carbohydrate antigen 19-9 (CA19-9) ≥ 37 U/mL (p = 0.042), postoperative complications (p = 0.043), and a high GBRS (p < 0.001) were prognostic factors for worse overall survival. On multivariate analysis, CA19-9 ≥ 37 U/mL (p = 0.039 and p = 0.043, respectively) and a high GBRS (p = 0.001 and p = 0.010, respectively) were independent risk factors for poor overall and recurrence-free survival. After propensity score-matched analysis, the GBRS precisely predicted prognosis of patients with GBC. CONCLUSIONS: The GBRS is an easy and novel prognostic predicting score. Our validation revealed good discrimination, suggesting its clinical utility to improve individualized prediction of survival for patients undergoing resection of GBC.","Source":"PubMed","category":"HUMAN","training_data":"Efficacy of the Gallbladder Cancer Predictive Risk Score Based on Pathological Findings: A Propensity Score-Matched Analysis BACKGROUND: The optimal prognostic predictive system for gallbladder carcinoma (GBC) has not been established. The gallbladder cancer predictive risk score (GBRS) based on pathological findings identifies incidental GBC patients at risk of recurrence. OBJECTIVE: We aimed to validate the prognostic ability of the GBRS in all GBC patients following curative surgery. METHODS: Fifty-six patients with GBC who underwent curative surgery between 1996 and 2016 were included in this study. Univariate and multivariate analyses were performed to determine prognostic factors associated with overall and recurrence-free survival, and propensity score-matched analysis was performed. RESULTS: The median patient age was 71.9 years, and 39.3% of patients were males. All patients underwent curative surgery (33.9%, simple cholecystectomy; 66.1%, more advanced procedures, such as hepatectomy; and 32.1%, bile duct reconstruction). On univariate analysis, preoperative carbohydrate antigen 19-9 (CA19-9) ≥ 37 U/mL (p = 0.042), postoperative complications (p = 0.043), and a high GBRS (p < 0.001) were prognostic factors for worse overall survival. On multivariate analysis, CA19-9 ≥ 37 U/mL (p = 0.039 and p = 0.043, respectively) and a high GBRS (p = 0.001 and p = 0.010, respectively) were independent risk factors for poor overall and recurrence-free survival. After propensity score-matched analysis, the GBRS precisely predicted prognosis of patients with GBC. CONCLUSIONS: The GBRS is an easy and novel prognostic predicting score. Our validation revealed good discrimination, suggesting its clinical utility to improve individualized prediction of survival for patients undergoing resection of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"advanced biliary tract carcinomas retrospective multicenter analysis first second line chemotherapy background gemcitabine cisplatin gem cddp combination demonstrated clear survival advantage gemcitabine alone become new standard advanced biliary tract carcinoma abtc however gemcitabine oxaliplatin gemox combination gemcitabine carboplatin gem carb combination regimens shown efficacy phase ii trials comparative study different platinum salts assessed efficacy safety different platinum based chemotherapies first line abtc patients also analysed second line chemotherapy methods sixty four consecutive patients abtc diagnosed 1998 2010 included analysis first line chemotherapy 44 patients received one day gemox regimen gemcitabine 1000 mg m2 oxaliplatin 100 mg m2 day 1 every 2 weeks 20 patients received gem carb regimen gemcitabine 1000 mg m2 days 1 8 carboplatin delivered according area curve auc 5 day 1 every 3 weeks second line total 16 patients received fluoropyrimidine based chemotherapy results gemox regimen median progression free survival pfs 3 7 months 95 ci 2 4 5 median overall survival os 10 5 months 95 ci 6 4 to14 7 main toxicity peripheral neuropathy 20 grade 2 7 grade 3 grade 3 4 haematological toxicities rare gem carb regimen pfs 2 5 months 95 ci 2 1 3 7 os 4 8 months 95 ci 3 7 5 8 main grade 3 4 toxicities haematological anaemia 45 thrombocytopenia 45 neutropenia 40 second line fluoropyrimidine based chemotherapy feasible fourth patients median os 5 3 months 95 ci 4 1 6 6 median pfs 4 0 months 95 ci 2 6 5 5 conclusions one day gemox regimen favourable toxicity profile alternative standard gem cddp regimen particular unfit patients cddp second line selective patients may benefit fluoropyrimidine based chemotherapy pubmed","probabilities":0.9799733,"Title":"Advanced biliary tract carcinomas: a retrospective multicenter analysis of first and second-line chemotherapy","Abstract":"BACKGROUND: Gemcitabine/Cisplatin (Gem/CDDP) combination has demonstrated a clear survival advantage over gemcitabine alone and has become a new standard in advanced Biliary Tract Carcinoma (aBTC). However, Gemcitabine/Oxaliplatin (GEMOX) combination and Gemcitabine/Carboplatin (Gem/Carb) combination regimens have shown efficacy in phase II trials and there is no comparative study between different platinum salts.We assessed the efficacy and safety of different platinum-based chemotherapies at first line in aBTC patients. We also analysed the second-line chemotherapy. METHODS: Sixty-four consecutive patients with aBTC diagnosed between 1998 and 2010 were included for analysis. At first line chemotherapy, 44 patients received one day GEMOX regimen (gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 Day 1, every 2 weeks), and 20 patients received Gem/Carb regimen (gemcitabine at 1000 mg/m2 Days 1 and 8 with carboplatin delivered according to an area-under-the-curve (AUC) 5 at day 1, every 3 weeks). At second line, a total of 16 patients received a fluoropyrimidine-based chemotherapy. RESULTS: With GEMOX regimen, median progression-free survival (PFS) was 3.7 months (95%CI, 2.4 to 5) and median overall survival (OS) was 10.5 months (95%CI, 6.4 to14.7). The main toxicity was peripheral neuropathy (20% grade 2 and 7% grade 3). Grade 3/4 haematological toxicities were rare.With Gem/Carb regimen, PFS was 2.5 months (95%CI, 2.1 to 3.7) and OS was 4.8 months (95%CI, 3.7 to 5.8). The main grade 3/4 toxicities were haematological: anaemia (45%), thrombocytopenia (45%), and neutropenia (40%).At second-line, fluoropyrimidine-based chemotherapy was feasible in only a fourth of the patients. The median OS was 5.3 months (95%CI, 4.1 to 6.6), and median PFS was 4.0 months (95%CI, 2.6 to 5.5). CONCLUSIONS: One day GEMOX regimen has a favourable toxicity profile and could be an alternative to standard Gem/CDDP regimen, in particular in unfit patients for CDDP.At second-line, selective patients may benefit from fluoropyrimidine-based chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Advanced biliary tract carcinomas: a retrospective multicenter analysis of first and second-line chemotherapy BACKGROUND: Gemcitabine/Cisplatin (Gem/CDDP) combination has demonstrated a clear survival advantage over gemcitabine alone and has become a new standard in advanced Biliary Tract Carcinoma (aBTC). However, Gemcitabine/Oxaliplatin (GEMOX) combination and Gemcitabine/Carboplatin (Gem/Carb) combination regimens have shown efficacy in phase II trials and there is no comparative study between different platinum salts.We assessed the efficacy and safety of different platinum-based chemotherapies at first line in aBTC patients. We also analysed the second-line chemotherapy. METHODS: Sixty-four consecutive patients with aBTC diagnosed between 1998 and 2010 were included for analysis. At first line chemotherapy, 44 patients received one day GEMOX regimen (gemcitabine 1000 mg/m2 and oxaliplatin 100 mg/m2 Day 1, every 2 weeks), and 20 patients received Gem/Carb regimen (gemcitabine at 1000 mg/m2 Days 1 and 8 with carboplatin delivered according to an area-under-the-curve (AUC) 5 at day 1, every 3 weeks). At second line, a total of 16 patients received a fluoropyrimidine-based chemotherapy. RESULTS: With GEMOX regimen, median progression-free survival (PFS) was 3.7 months (95%CI, 2.4 to 5) and median overall survival (OS) was 10.5 months (95%CI, 6.4 to14.7). The main toxicity was peripheral neuropathy (20% grade 2 and 7% grade 3). Grade 3/4 haematological toxicities were rare.With Gem/Carb regimen, PFS was 2.5 months (95%CI, 2.1 to 3.7) and OS was 4.8 months (95%CI, 3.7 to 5.8). The main grade 3/4 toxicities were haematological: anaemia (45%), thrombocytopenia (45%), and neutropenia (40%).At second-line, fluoropyrimidine-based chemotherapy was feasible in only a fourth of the patients. The median OS was 5.3 months (95%CI, 4.1 to 6.6), and median PFS was 4.0 months (95%CI, 2.6 to 5.5). CONCLUSIONS: One day GEMOX regimen has a favourable toxicity profile and could be an alternative to standard Gem/CDDP regimen, in particular in unfit patients for CDDP.At second-line, selective patients may benefit from fluoropyrimidine-based chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"chemoembolization intrahepatic cholangiocarcinoma cisplatinum doxorubicin mitomycin c ethiodol polyvinyl alcohol 2 center study background unresectable intrahepatic cholangiocarcinoma poor prognosis median survival 5 8 months without treatment response survival chemoembolization evaluated methods lobar segmental chemoembolization cisplatinum doxorubicin mitomycin c ethiodol polyvinyl alcohol particles performed monthly intervals 1 4 sessions entire intrahepatic tumor burden treated cross sectional imaging clinical laboratory evaluation performed treatment 1 month treatment every 3 months second cycle treatment performed intrahepatic recurrence toxicity assessed using nci ctc v 3 0 response evaluated using recist criteria survival estimated kaplan meier analysis results sixty two patients treated thirty seven pathologically proven cholangiocarcinoma 25 poorly differentiated adenocarcinoma unknown primary likely cholangiocarcinoma one hundred twenty two total procedures performed initial cycle treatment mean 2 0 per patient twenty patients received second cycle total 165 procedures 5 major complications thirty day disease specific mortality 0 forty five 62 patients evaluable morphologic response completion initial cycle 11 n 5 partial responses 64 n 29 stable 24 n 11 progressed median time progression first chemoembolization 8 months 28 free progression 12 months median survival time diagnosis 20 months 1 2 3 year survival 75 39 17 respectively median survival time first chemoembolization 15 months 1 2 3 year survival 61 27 8 respectively statistically significant difference survival patients cholangiocarcinoma poorly differentiated adenocarcinoma patients also received systemic chemotherapy improved overall survival median 28 vs 16 months p 02 hr 1 94 95 ci 1 13 3 33 conclusions chemoembolization provided local disease control pr sd intrahepatic cholangiocarcinoma adenocarcinoma unknown primary 76 overall survival chemoembolization showed best outcomes receiving multidisciplinary integrated liver directed systemic therapies pubmed","probabilities":0.9799733,"Title":"Chemoembolization of intrahepatic cholangiocarcinoma with cisplatinum, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol: a 2-center study","Abstract":"BACKGROUND: Unresectable intrahepatic cholangiocarcinoma has a poor prognosis, with a median survival of 5 to 8 months without treatment. Response and survival after chemoembolization were evaluated. METHODS: Lobar or segmental chemoembolization with cisplatinum, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol particles was performed at monthly intervals for 1-4 sessions until the entire intrahepatic tumor burden was treated. Cross-sectional imaging and clinical and laboratory evaluation were performed before treatment, 1 month after treatment, and then every 3 months. A second cycle of treatment was performed for intrahepatic recurrence. Toxicity was assessed using NCI CTC v.3.0. Response was evaluated using RECIST criteria, and survival was estimated with Kaplan-Meier analysis. RESULTS: Sixty-two patients were treated. Thirty-seven had pathologically proven cholangiocarcinoma, and 25 had poorly differentiated adenocarcinoma of unknown primary, likely cholangiocarcinoma. One hundred and twenty-two total procedures were performed during the initial cycle of treatment (mean, 2.0 per patient). Twenty patients received a second cycle, for a total of 165 procedures. There were 5 major complications. Thirty-day disease-specific mortality was 0%. Forty-five of 62 patients were evaluable for morphologic response after completion of their initial cycle: 11% (n = 5) partial responses, 64% (n = 29) stable, and 24% (n = 11) progressed. Median time to progression from first chemoembolization was 8 months, with 28% free of progression at 12 months. Median survival from time of diagnosis was 20 months, with 1-, 2-, and 3-year survival of 75%, 39%, and 17%, respectively. Median survival from time of first chemoembolization was 15 months, with 1-, 2-, and 3-year survival of 61%, 27%, and 8%, respectively. There was no statistically significant difference in survival between patients with cholangiocarcinoma and those with poorly differentiated adenocarcinoma. Patients who also received systemic chemotherapy had improved overall survival (median 28 vs 16 months, P = .02; HR, 1.94; 95% CI, 1.13-3.33). CONCLUSIONS: Chemoembolization provided local disease control (PR + SD) of intrahepatic cholangiocarcinoma and adenocarcinoma of unknown primary in 76%. Overall survival after chemoembolization showed the best outcomes for those receiving multidisciplinary integrated liver-directed and systemic therapies.","Source":"PubMed","category":"HUMAN","training_data":"Chemoembolization of intrahepatic cholangiocarcinoma with cisplatinum, doxorubicin, mitomycin C, ethiodol, and polyvinyl alcohol: a 2-center study BACKGROUND: Unresectable intrahepatic cholangiocarcinoma has a poor prognosis, with a median survival of 5 to 8 months without treatment. Response and survival after chemoembolization were evaluated. METHODS: Lobar or segmental chemoembolization with cisplatinum, doxorubicin, mitomycin-C, ethiodol, and polyvinyl alcohol particles was performed at monthly intervals for 1-4 sessions until the entire intrahepatic tumor burden was treated. Cross-sectional imaging and clinical and laboratory evaluation were performed before treatment, 1 month after treatment, and then every 3 months. A second cycle of treatment was performed for intrahepatic recurrence. Toxicity was assessed using NCI CTC v.3.0. Response was evaluated using RECIST criteria, and survival was estimated with Kaplan-Meier analysis. RESULTS: Sixty-two patients were treated. Thirty-seven had pathologically proven cholangiocarcinoma, and 25 had poorly differentiated adenocarcinoma of unknown primary, likely cholangiocarcinoma. One hundred and twenty-two total procedures were performed during the initial cycle of treatment (mean, 2.0 per patient). Twenty patients received a second cycle, for a total of 165 procedures. There were 5 major complications. Thirty-day disease-specific mortality was 0%. Forty-five of 62 patients were evaluable for morphologic response after completion of their initial cycle: 11% (n = 5) partial responses, 64% (n = 29) stable, and 24% (n = 11) progressed. Median time to progression from first chemoembolization was 8 months, with 28% free of progression at 12 months. Median survival from time of diagnosis was 20 months, with 1-, 2-, and 3-year survival of 75%, 39%, and 17%, respectively. Median survival from time of first chemoembolization was 15 months, with 1-, 2-, and 3-year survival of 61%, 27%, and 8%, respectively. There was no statistically significant difference in survival between patients with cholangiocarcinoma and those with poorly differentiated adenocarcinoma. Patients who also received systemic chemotherapy had improved overall survival (median 28 vs 16 months, P = .02; HR, 1.94; 95% CI, 1.13-3.33). CONCLUSIONS: Chemoembolization provided local disease control (PR + SD) of intrahepatic cholangiocarcinoma and adenocarcinoma of unknown primary in 76%. Overall survival after chemoembolization showed the best outcomes for those receiving multidisciplinary integrated liver-directed and systemic therapies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative postoperative ca19 9 levels predict survival early recurrence patients resectable hilar cholangiocarcinoma background investigate predictive values preoperative postoperative serum ca19 9 levels survival prognostic factors including early recurrence patients resectable hilar cholangiocarcinoma results univariate analysis increased preoperative postoperative ca19 9 levels light different cut points 37 100 150 200 400 1000 u ml significantly associated poor survival outcomes cut point 150 u ml showed strongest predictive value p 0 001 preoperative postoperative increase ca19 9 level also correlated poor survival outcome p 0 001 multivariate analysis preoperative ca19 9 level 150 u ml significantly associated lymph node metastasis 3 471 95 ci 1 216 9 905 p 0 020 early recurrence 8 280 95 ci 2 391 28 674 p 0 001 meanwhile postoperative ca19 9 level 150 u ml also correlated early recurrence 4 006 95 ci 1 107 14 459 p 0 034 materials methods ninety eight patients undergone curative surgery hilar cholangiocarcinoma 1995 2014 institution selected study correlations preoperative postoperative serum ca19 9 levels basis different cut points survival various tumor factors retrospectively analyzed univariate multivariate methods conclusions patients resectable hilar cholangiocarcinoma serum ca19 9 predict survival early recurrence patients increased preoperative postoperative ca19 9 levels poor survival outcomes higher tendency early recurrence stn","probabilities":0.9799733,"Title":"Can Preoperative And Postoperative Ca19-9 Levels Predict Survival And Early Recurrence In Patients With Resectable Hilar Cholangiocarcinoma?","Abstract":"Background: To investigate the predictive values of preoperative and postoperative serum CA19-9 levels on survival and other prognostic factors including early recurrence in patients with resectable hilar cholangiocarcinoma. \r\n\r\n Results: In univariate analysis, increased preoperative and postoperative CA19-9 levels in the light of different cut-off points (37, 100, 150, 200, 400, 1000 U/ml) were significantly associated with poor survival outcomes, of which the cut-off point of 150 U/ml showed the strongest predictive value (both P < 0.001). Preoperative to postoperative increase in CA19-9 level was also correlated with poor survival outcome (P < 0.001). In multivariate analysis, preoperative CA19-9 level > 150 U/ml was significantly associated with lymph node metastasis (OR = 3.471, 95% CI 1.216-9.905; P = 0.020) and early recurrence (OR = 8.280, 95% CI 2.391-28.674; P = 0.001). Meanwhile, postoperative CA19-9 level > 150 U/ml was also correlated with early recurrence (OR = 4.006, 95% CI 1.107-14.459; P = 0.034). \r\n\r\n Materials and methods: Ninety-eight patients who had undergone curative surgery for hilar cholangiocarcinoma between 1995 and 2014 in our institution were selected for the study. The correlations of preoperative and postoperative serum CA19-9 levels on the basis of different cut-off points with survival and various tumor factors were retrospectively analyzed with univariate and multivariate methods. \r\n\r\n Conclusions: In patients with resectable hilar cholangiocarcinoma, serum CA19-9 predict survival and early recurrence. Patients with increased preoperative and postoperative CA19-9 levels have poor survival outcomes and higher tendency of early recurrence.","Source":"STN","category":"HUMAN","training_data":"Can Preoperative And Postoperative Ca19-9 Levels Predict Survival And Early Recurrence In Patients With Resectable Hilar Cholangiocarcinoma? Background: To investigate the predictive values of preoperative and postoperative serum CA19-9 levels on survival and other prognostic factors including early recurrence in patients with resectable hilar cholangiocarcinoma. \r\n\r\n Results: In univariate analysis, increased preoperative and postoperative CA19-9 levels in the light of different cut-off points (37, 100, 150, 200, 400, 1000 U/ml) were significantly associated with poor survival outcomes, of which the cut-off point of 150 U/ml showed the strongest predictive value (both P < 0.001). Preoperative to postoperative increase in CA19-9 level was also correlated with poor survival outcome (P < 0.001). In multivariate analysis, preoperative CA19-9 level > 150 U/ml was significantly associated with lymph node metastasis (OR = 3.471, 95% CI 1.216-9.905; P = 0.020) and early recurrence (OR = 8.280, 95% CI 2.391-28.674; P = 0.001). Meanwhile, postoperative CA19-9 level > 150 U/ml was also correlated with early recurrence (OR = 4.006, 95% CI 1.107-14.459; P = 0.034). \r\n\r\n Materials and methods: Ninety-eight patients who had undergone curative surgery for hilar cholangiocarcinoma between 1995 and 2014 in our institution were selected for the study. The correlations of preoperative and postoperative serum CA19-9 levels on the basis of different cut-off points with survival and various tumor factors were retrospectively analyzed with univariate and multivariate methods. \r\n\r\n Conclusions: In patients with resectable hilar cholangiocarcinoma, serum CA19-9 predict survival and early recurrence. Patients with increased preoperative and postoperative CA19-9 levels have poor survival outcomes and higher tendency of early recurrence. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact circulating tumor cells patients ampullary cancer circulating tumor cells ctcs important topic investigation basic clinical cancer research prospective study evaluated clinical role ctcs ampullary cancer analyzed blood samples 62 consecutively diagnosed patients ampullary adenocarcinoma 24 healthy controls ctc content combined data immunostaining cd45 4 6 diamidino 2 phenylindole dapi fluorescence situ hybridization chromosome 8 centromere cep8 probe used identify ctcs cells cd45 dapi cep8 2 considered ctcs cox proportional hazards model used assess relationship ctcs clinical characteristics patient outcomes detected 2 ctcs 3 2 ml whole blood 43 62 patients 69 4 well 5 ctcs 3 2 ml 16 patients 25 8 ctc cutoff value 2 cells 3 2 ml achieved 69 4 sensitivity 95 8 specificity diagnostic tool ctcs associated tumor burden ctc levels 3 3 2 ml hazard ratio hr 2 5 95 confidence interval ci 1 2 5 2 p 0 014 5 3 2 ml hr 3 5 95 ci 1 7 7 3 p 0 001 associated shorter disease free survival moreover 3 ctcs 3 2 ml hr 2 7 95 ci 1 2 6 3 p 0 019 5 ctcs 3 2 ml hr 3 8 95 ci 1 8 8 5 p 0 001 predictive shorter overall survival ctc assessment may help identify patients ampullary cancer high risk unfavorable outcome pubmed","probabilities":0.9799733,"Title":"Prognostic impact of circulating tumor cells in patients with ampullary cancer","Abstract":"Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4',6-diamidino-2-phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45-/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2-5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7-7.3, p < 0.001) were both associated with shorter disease-free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2-6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8-8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic impact of circulating tumor cells in patients with ampullary cancer Circulating tumor cells (CTCs) are an important topic of investigation for both basic and clinical cancer research. In this prospective study, we evaluated the clinical role of CTCs in ampullary cancer. We analyzed blood samples from 62 consecutively diagnosed patients with ampullary adenocarcinoma and 24 healthy controls for their CTC content. Combined data from immunostaining of CD45, 4',6-diamidino-2-phenylindole (DAPI), and fluorescence in situ hybridization with a chromosome 8 centromere (CEP8) probe were used to identify CTCs; cells that were CD45-/DAPI+/CEP8>2 were considered CTCs. The Cox proportional hazards model was used to assess the relationship between CTCs, clinical characteristics, and patient outcomes. We detected ≥2 CTCs/3.2 ml whole blood in 43 of 62 patients (69.4%), as well as ≥5 CTCs/3.2 ml in 16 of these patients (25.8%). A CTC cutoff value of 2 cells/3.2 ml achieved 69.4% sensitivity and 95.8% specificity as a diagnostic tool; CTCs were associated with tumor burden. CTC levels ≥3/3.2 ml (hazard ratio [HR]: 2.5, 95% confidence interval [CI]: (1.2-5.2), p = 0.014) and ≥5/3.2 ml (HR: 3.5, 95% CI: 1.7-7.3, p < 0.001) were both associated with shorter disease-free survival. Moreover, ≥3 CTCs/3.2 ml (HR: 2.7, 95% CI: 1.2-6.3, p = 0.019) and ≥5 CTCs/3.2 ml (HR: 3.8, 95% CI: 1.8-8.5, p < 0.001) were predictive of shorter overall survival. CTC assessment may help identify patients with ampullary cancer who are at high risk of an unfavorable outcome. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression prognostic value soluble cd97 ligand cd55 intrahepatic cholangiocarcinoma incidence rate intrahepatic cholangiocarcinoma rising treatment options limited therefore new biological markers intrahepatic cholangiocarcinoma needed immunohistochemistry enzyme linked immunosorbent assay applied analyze expressions cd97 cd55 soluble cd97 71 patients intrahepatic cholangiocarcinoma 10 patients hepatolithiasis cd97 cd55 expressed hepatolithiatic tissues positive expression observed 76 1 54 71 70 4 50 71 intrahepatic cholangiocarcinoma patients univariate analyses indicated positive expressions cd97 cd55 related short intrahepatic cholangiocarcinoma survival patients p 0 001 furthermore cd97 cd55 expressions biliary soluble cd97 levels significantly associated histological grade p 0 004 0 002 0 012 respectively lymph node metastases p 0 020 0 038 0 001 respectively venous invasion p 0 003 0 002 0 001 respectively multivariate analyses indicated lymph node metastases hazard ratio 2 407 p 0 003 positive cd55 expression hazard ratio 4 096 p 0 003 biliary soluble cd97 levels hazard ratio 2 434 p 0 002 independent risk factors intrahepatic cholangiocarcinoma survival receiver operating characteristic roc curve analysis indicated cutoff values biliary soluble cd97 1 15 u ml diagnostic value predicting lymph node metastasis sensitivity 87 5 specificity 51 3 intrahepatic cholangiocarcinoma patient death within 60 months cutoff value 0 940 u ml diagnostic value sensitivity 89 3 specificity 93 3 biliary soluble cd97 may new biological marker early diagnosis prediction lymph node metastasis poor prognosis discovery therapeutic target stn","probabilities":0.88235295,"Title":"Expression And Prognostic Value Of Soluble Cd97 And Its Ligand Cd55 In Intrahepatic Cholangiocarcinoma","Abstract":"The incidence rate of intrahepatic cholangiocarcinoma is rising, and treatment options are limited. Therefore, new biological markers of intrahepatic cholangiocarcinoma are needed. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to analyze the expressions of CD97, CD55, and soluble CD97 in 71 patients with intrahepatic cholangiocarcinoma and 10 patients with hepatolithiasis. CD97 and CD55 were not expressed in hepatolithiatic tissues, but positive expression was observed in 76.1% (54/71) and 70.4% (50/71) of intrahepatic cholangiocarcinoma patients. The univariate analyses indicated that the positive expressions of CD97 and CD55 were related to short intrahepatic cholangiocarcinoma survival of patients (both p = 0.001). Furthermore, CD97 and CD55 expressions and biliary soluble CD97 levels were significantly associated with histological grade (p = 0.004, 0.002, and 0.012, respectively), lymph node metastases (p = 0.020, 0.038, and 0.001, respectively), and venous invasion (p = 0.003, 0.002, and 0.001, respectively). The multivariate analyses indicated that lymph node metastases (hazard ratio: 2.407, p = 0.003), positive CD55 expression (hazard ratio: 4.096, p = 0.003), and biliary soluble CD97 levels (hazard ratio: 2.434, p = 0.002) were independent risk factors for the intrahepatic cholangiocarcinoma survival. The receiver operating characteristic (ROC) curve analysis indicated that when the cutoff values of biliary soluble CD97 were 1.15 U/mL, the diagnostic value for predicting lymph node metastasis had a sensitivity of 87.5% and a specificity of 51.3%. For intrahepatic cholangiocarcinoma patient death within 60 months at a cutoff value of 0.940 U/mL, the diagnostic value sensitivity was 89.3% and the specificity was 93.3%. Biliary soluble CD97 may be a new biological marker for early diagnosis, prediction of lymph node metastasis and poor prognosis, and discovery of a therapeutic target.","Source":"STN","category":"HUMAN","training_data":"Expression And Prognostic Value Of Soluble Cd97 And Its Ligand Cd55 In Intrahepatic Cholangiocarcinoma The incidence rate of intrahepatic cholangiocarcinoma is rising, and treatment options are limited. Therefore, new biological markers of intrahepatic cholangiocarcinoma are needed. Immunohistochemistry and enzyme-linked immunosorbent assay were applied to analyze the expressions of CD97, CD55, and soluble CD97 in 71 patients with intrahepatic cholangiocarcinoma and 10 patients with hepatolithiasis. CD97 and CD55 were not expressed in hepatolithiatic tissues, but positive expression was observed in 76.1% (54/71) and 70.4% (50/71) of intrahepatic cholangiocarcinoma patients. The univariate analyses indicated that the positive expressions of CD97 and CD55 were related to short intrahepatic cholangiocarcinoma survival of patients (both p = 0.001). Furthermore, CD97 and CD55 expressions and biliary soluble CD97 levels were significantly associated with histological grade (p = 0.004, 0.002, and 0.012, respectively), lymph node metastases (p = 0.020, 0.038, and 0.001, respectively), and venous invasion (p = 0.003, 0.002, and 0.001, respectively). The multivariate analyses indicated that lymph node metastases (hazard ratio: 2.407, p = 0.003), positive CD55 expression (hazard ratio: 4.096, p = 0.003), and biliary soluble CD97 levels (hazard ratio: 2.434, p = 0.002) were independent risk factors for the intrahepatic cholangiocarcinoma survival. The receiver operating characteristic (ROC) curve analysis indicated that when the cutoff values of biliary soluble CD97 were 1.15 U/mL, the diagnostic value for predicting lymph node metastasis had a sensitivity of 87.5% and a specificity of 51.3%. For intrahepatic cholangiocarcinoma patient death within 60 months at a cutoff value of 0.940 U/mL, the diagnostic value sensitivity was 89.3% and the specificity was 93.3%. Biliary soluble CD97 may be a new biological marker for early diagnosis, prediction of lymph node metastasis and poor prognosis, and discovery of a therapeutic target. STN","prediction_labels":"HUMAN"},{"cleaned":"dickkopf homolog 3 dkk3 acts potential tumor suppressor gallbladder cancer gallbladder cancer gbc common malignancy biliary tract cancers incidence rising rapidly worldwide prognosis disease dismal symptoms non specific leading definitive diagnosis late stage loss dkk3 gene associated possible tumor suppressor role human cancers role regulation dkk3 gbc studied found dkk3 expression levels low gbc patients cell lines treatment gbc cell lines demethylating agent 5 aza 2 deoxycytidine enhances expression establishing impact methylation dkk3 expression observed low expression dkk3 gallbladder adenocarcinoma tumors highly invasive gbc cell lines showed overexpression dkk3 decrease cell invasion proliferation colony forming ability gbc cells data thus demonstrated dkk3 gene potential tumor suppressor gene gbc aberrant promoter methylation involved downregulation may play role tumorigenesis aggressiveness gbc stn","probabilities":0.9467213,"Title":"Dickkopf Homolog 3 (Dkk3) Acts As A Potential Tumor Suppressor In Gallbladder Cancer","Abstract":"Gallbladder cancer (GBC) is a common malignancy of biliary tract cancers and its incidence has been rising rapidly worldwide. The prognosis for this disease is dismal as most of the symptoms are non-specific leading to a definitive diagnosis only at a late stage. Loss of DKK3 gene is associated with a possible tumor suppressor role in human cancers. The role and regulation of DKK3 in GBC have not been studied. We found that DKK3 expression levels were low in GBC patients and cell lines. Treatment of GBC cell lines with demethylating agent 5-Aza- 2'-deoxycytidine enhances its expression, establishing impact of methylation on DKK3 expression. We observed low expression of DKK3 in gallbladder adenocarcinoma tumors and highly invasive GBC cell lines. We showed that overexpression of DKK3 can decrease cell invasion, proliferation, and colony forming ability of GBC cells. Our data thus demonstrated the DKK3 gene is a potential tumor suppressor gene in GBC and aberrant promoter methylation could be involved in its downregulation, which may play a role in the tumorigenesis and aggressiveness of GBC.","Source":"STN","category":"ANIMAL","training_data":"Dickkopf Homolog 3 (Dkk3) Acts As A Potential Tumor Suppressor In Gallbladder Cancer Gallbladder cancer (GBC) is a common malignancy of biliary tract cancers and its incidence has been rising rapidly worldwide. The prognosis for this disease is dismal as most of the symptoms are non-specific leading to a definitive diagnosis only at a late stage. Loss of DKK3 gene is associated with a possible tumor suppressor role in human cancers. The role and regulation of DKK3 in GBC have not been studied. We found that DKK3 expression levels were low in GBC patients and cell lines. Treatment of GBC cell lines with demethylating agent 5-Aza- 2'-deoxycytidine enhances its expression, establishing impact of methylation on DKK3 expression. We observed low expression of DKK3 in gallbladder adenocarcinoma tumors and highly invasive GBC cell lines. We showed that overexpression of DKK3 can decrease cell invasion, proliferation, and colony forming ability of GBC cells. Our data thus demonstrated the DKK3 gene is a potential tumor suppressor gene in GBC and aberrant promoter methylation could be involved in its downregulation, which may play a role in the tumorigenesis and aggressiveness of GBC. STN","prediction_labels":"ANIMAL"},{"cleaned":"impact intrapancreatic extrapancreatic bile duct involvement survival following pancreatoduodenectomy common bile duct cancer background clinicopathological factors influence survival following pancreatoduodenectomy pd common bile duct cbd cancer well known study aimed investigate effect tumour involvement intrapancreatic versus extrapancreatic cbd margin status overall os disease free dfs survival methods retrospective study patients underwent pd cbd cancer 2001 2009 pathological examination performed according previously described standardized protocol based axial slicing clinicopathological data outcome terms margin status dfs os compared cancers involving exclusively intrapancreatic cbd cbdin involving extrapancreatic cbd isolation combined invasion intrapancreatic part duct cbdex results total 66 patients enrolled cbd cancers locally advanced 97 per cent pathological p t3 76 per cent pn1 microscopic margin involvement r1 frequent cbdex cbdin cancers 34 39 versus 13 27 p 0 001 often multifocal p 0 001 frequently affected periductal margin p 0 005 venous resection often required cbdex cancers p 0 009 cbdex cancers associated worse os median 21 versus 28 months p 0 020 dfs 14 versus 31 months p 0 015 rate site recurrence differ metastasis two lymph nodes independent predictor os dfs conclusion cbdex cancer associated higher rate r1 resection venous resection pd worse outcome cbdin cancer pubmed","probabilities":0.9799733,"Title":"Impact of intrapancreatic or extrapancreatic bile duct involvement on survival following pancreatoduodenectomy for common bile duct cancer","Abstract":"BACKGROUND: The clinicopathological factors that influence survival following pancreatoduodenectomy (PD) for common bile duct (CBD) cancer are not well known. This study aimed to investigate the effect of tumour involvement of the intrapancreatic versus extrapancreatic CBD on margin status, overall (OS) and disease-free (DFS) survival. METHODS: This was a retrospective study of patients who underwent PD for CBD cancer between 2001 and 2009. Pathological examination was performed according to a previously described standardized protocol based on axial slicing. Clinicopathological data and outcome in terms of margin status, DFS and OS were compared between cancers involving exclusively the intrapancreatic CBD (CBDin) and those involving the extrapancreatic CBD, in isolation or combined with invasion of the intrapancreatic part of the duct (CBDex). RESULTS: A total of 66 patients were enrolled. Most CBD cancers were locally advanced (97 per cent pathological (p) T3, 76 per cent pN1). Microscopic margin involvement (R1) was more frequent in CBDex than in CBDin cancers (34 of 39 versus 13 of 27; P = 0.001), more often multifocal (P < 0.001) and more frequently affected the periductal margin (P = 0.005). Venous resection was more often required for CBDex cancers (P = 0.009). CBDex cancers were associated with worse OS (median 21 versus 28 months; P = 0.020) and DFS (14 versus 31 months; P = 0.015), but the rate and site of recurrence did not differ. Metastasis to more than two lymph nodes was an independent predictor of OS and DFS. CONCLUSION: CBDex cancer is associated with a higher rate of R1 resection and venous resection after PD, and has a worse outcome than CBDin cancer.","Source":"PubMed","category":"HUMAN","training_data":"Impact of intrapancreatic or extrapancreatic bile duct involvement on survival following pancreatoduodenectomy for common bile duct cancer BACKGROUND: The clinicopathological factors that influence survival following pancreatoduodenectomy (PD) for common bile duct (CBD) cancer are not well known. This study aimed to investigate the effect of tumour involvement of the intrapancreatic versus extrapancreatic CBD on margin status, overall (OS) and disease-free (DFS) survival. METHODS: This was a retrospective study of patients who underwent PD for CBD cancer between 2001 and 2009. Pathological examination was performed according to a previously described standardized protocol based on axial slicing. Clinicopathological data and outcome in terms of margin status, DFS and OS were compared between cancers involving exclusively the intrapancreatic CBD (CBDin) and those involving the extrapancreatic CBD, in isolation or combined with invasion of the intrapancreatic part of the duct (CBDex). RESULTS: A total of 66 patients were enrolled. Most CBD cancers were locally advanced (97 per cent pathological (p) T3, 76 per cent pN1). Microscopic margin involvement (R1) was more frequent in CBDex than in CBDin cancers (34 of 39 versus 13 of 27; P = 0.001), more often multifocal (P < 0.001) and more frequently affected the periductal margin (P = 0.005). Venous resection was more often required for CBDex cancers (P = 0.009). CBDex cancers were associated with worse OS (median 21 versus 28 months; P = 0.020) and DFS (14 versus 31 months; P = 0.015), but the rate and site of recurrence did not differ. Metastasis to more than two lymph nodes was an independent predictor of OS and DFS. CONCLUSION: CBDex cancer is associated with a higher rate of R1 resection and venous resection after PD, and has a worse outcome than CBDin cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"neutrophil lymphocyte ratio predicts prognosis neoadjuvant chemotherapy resection intrahepatic cholangiocarcinoma background previous studies demonstrated strong association preoperative neutrophil lymphocyte ratio outcomes patients resected hepatocellular carcinoma colorectal liver metastases however predictive ability neutrophil lymphocyte ratio patients intrahepatic cholangiocarcinoma especially treated preoperative chemotherapy less well described methods clinicopathological characteristics overall survival recurrence free survival patients intrahepatic cholangiocarcinoma resected 2000 2015 compared elevated 3 0 normal 3 0 neutrophil lymphocyte ratio results among 119 patients met inclusion criteria 64 53 8 neutrophil lymphocyte ratio 3 0 55 46 2 neutrophil lymphocyte ratio 3 0 patients neutrophil lymphocyte ratio 3 0 likely female lymph node metastasis p 05 cumulative 5 year overall survival recurrence free survival rates 87 60 respectively patients neutrophil lymphocyte ratio 3 0 compared 64 39 respectively patients neutrophil lymphocyte ratio 3 0 p 049 038 among 43 patients treated preoperative chemotherapy resection 21 48 8 neutrophil lymphocyte ratio 3 0 22 51 2 neutrophil lymphocyte ratio 3 0 subgroup cumulative 5 year overall survival recurrence free survival rates 95 70 respectively patients neutrophil lymphocyte ratio 3 0 compared 50 26 respectively patients neutrophil lymphocyte ratio 3 0 p 002 p 004 multivariate analysis neutrophil lymphocyte ratio 3 0 associated significantly worse overall survival among patients well overall survival recurrence free survival among subgroup received preoperative chemotherapy conclusion neutrophil lymphocyte ratio associated independently worse survival patients intrahepatic cholangiocarcinoma undergoing resection neoadjuvant chemotherapy prior resection pubmed","probabilities":0.9799733,"Title":"Neutrophil-to-lymphocyte ratio predicts prognosis after neoadjuvant chemotherapy and resection of intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Previous studies have demonstrated a strong association between the preoperative neutrophil-to-lymphocyte ratio and the outcomes of patients with resected hepatocellular carcinoma and colorectal liver metastases. However, the predictive ability of neutrophil-to-lymphocyte ratio in patients with intrahepatic cholangiocarcinoma, especially those treated with preoperative chemotherapy, has been less well described. METHODS: The clinicopathological characteristics, overall survival, and recurrence free survival of all patients with intrahepatic cholangiocarcinoma resected between 2000-2015, were compared between those with elevated (≥3.0) and normal (<3.0) neutrophil-to-lymphocyte ratio. RESULTS: Among 119 patients who met the inclusion criteria, 64 (53.8%) had neutrophil-to-lymphocyte ratio <3.0 and 55 (46.2%) had neutrophil-to-lymphocyte ratio ≥3.0. Patients with neutrophil-to-lymphocyte ratio ≥3.0 were more likely to be female and have lymph node metastasis (P < .05). Cumulative 5-year overall survival and recurrence free survival rates were 87% and 60%, respectively in patients with neutrophil-to-lymphocyte ratio <3.0, compared with 64% and 39%, respectively in patients with neutrophil-to-lymphocyte ratio ≥3.0 (P = .049 and .038). Among 43 patients treated with preoperative chemotherapy and resection, 21 (48.8%) had neutrophil-to-lymphocyte ratio <3.0 and 22 (51.2%) had neutrophil-to-lymphocyte ratio ≥3.0. In this subgroup, cumulative 5-year overall survival and recurrence free survival rates were 95% and 70%, respectively in the patients with neutrophil-to-lymphocyte ratio <3.0 compared with 50% and 26%, respectively in the patients with neutrophil-to-lymphocyte ratio ≥3.0 (P = .002 and P = .004). On multivariate analysis, a neutrophil-to-lymphocyte ratio ≥3.0 was associated significantly with worse overall survival among all patients as well as overall survival and recurrence free survival among the subgroup who received preoperative chemotherapy. CONCLUSION: Neutrophil-to-lymphocyte ratio is associated independently with worse survival in patients with intrahepatic cholangiocarcinoma undergoing resection or neoadjuvant chemotherapy prior to resection.","Source":"PubMed","category":"HUMAN","training_data":"Neutrophil-to-lymphocyte ratio predicts prognosis after neoadjuvant chemotherapy and resection of intrahepatic cholangiocarcinoma BACKGROUND: Previous studies have demonstrated a strong association between the preoperative neutrophil-to-lymphocyte ratio and the outcomes of patients with resected hepatocellular carcinoma and colorectal liver metastases. However, the predictive ability of neutrophil-to-lymphocyte ratio in patients with intrahepatic cholangiocarcinoma, especially those treated with preoperative chemotherapy, has been less well described. METHODS: The clinicopathological characteristics, overall survival, and recurrence free survival of all patients with intrahepatic cholangiocarcinoma resected between 2000-2015, were compared between those with elevated (≥3.0) and normal (<3.0) neutrophil-to-lymphocyte ratio. RESULTS: Among 119 patients who met the inclusion criteria, 64 (53.8%) had neutrophil-to-lymphocyte ratio <3.0 and 55 (46.2%) had neutrophil-to-lymphocyte ratio ≥3.0. Patients with neutrophil-to-lymphocyte ratio ≥3.0 were more likely to be female and have lymph node metastasis (P < .05). Cumulative 5-year overall survival and recurrence free survival rates were 87% and 60%, respectively in patients with neutrophil-to-lymphocyte ratio <3.0, compared with 64% and 39%, respectively in patients with neutrophil-to-lymphocyte ratio ≥3.0 (P = .049 and .038). Among 43 patients treated with preoperative chemotherapy and resection, 21 (48.8%) had neutrophil-to-lymphocyte ratio <3.0 and 22 (51.2%) had neutrophil-to-lymphocyte ratio ≥3.0. In this subgroup, cumulative 5-year overall survival and recurrence free survival rates were 95% and 70%, respectively in the patients with neutrophil-to-lymphocyte ratio <3.0 compared with 50% and 26%, respectively in the patients with neutrophil-to-lymphocyte ratio ≥3.0 (P = .002 and P = .004). On multivariate analysis, a neutrophil-to-lymphocyte ratio ≥3.0 was associated significantly with worse overall survival among all patients as well as overall survival and recurrence free survival among the subgroup who received preoperative chemotherapy. CONCLUSION: Neutrophil-to-lymphocyte ratio is associated independently with worse survival in patients with intrahepatic cholangiocarcinoma undergoing resection or neoadjuvant chemotherapy prior to resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term survival among mismatch repair deficient cholangiocarcinomas associated lynch syndrome purpose patients lynch syndrome ls significantly elevated lifetime risk developing biliary tract cancers btcs compared general population however studies characterized clinical characteristics genetic features long term outcomes mismatch repair deficient dmmr cholangiocarcinomas associated ls methods retrospective review prospectively maintained familial high risk gi cancer clinic database identified patients btcs evaluated 2006 2016 carried germline mutations mlh1 msh2 msh6 pms2 results eleven patients btcs identified four perihilar four intrahepatic one extrahepatic one gallbladder one ampulla vater patients underlying germline mutations personal history ls associated malignancy commonly 63 3 colorectal cancer ten 90 9 patients surgically explored margin negative resection possible seven 63 3 chemotherapy 90 9 chemoradiation 45 5 administered patients among seven patients presenting non metastatic disease underwent surgical resection curative intent 5 year overall survival rate 53 3 median overall survival four patients treated curative intent 17 2 months conclusions dmmr biliary tract cancers associated ls rare long term outcomes may favorable contemporaneous cohorts non lynch associated cholangiocarcinomas given emerging promise immunotherapy patients dmmr malignancies tumor testing dmmr followed confirmatory germline testing considered patients btc personal history ls cancers stn","probabilities":0.9799733,"Title":"Long-Term Survival Among Mismatch Repair Deficient Cholangiocarcinomas Associated With Lynch Syndrome","Abstract":"Purpose: Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS. \r\n\r\n Methods: A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2. \r\n\r\n Results: Eleven patients with BTCs were identified: four perihilar, four intrahepatic, one extrahepatic, one gallbladder, and one ampulla of Vater. All patients had underlying germline mutations and a personal history of a LS-associated malignancy, most commonly (63.3%) colorectal cancer. Ten (90.9%) patients were surgically explored, and margin negative resection was possible in seven (63.3%). Chemotherapy (90.9%) and/or chemoradiation (45.5%) was administered to most patients. Among the seven patients presenting with non-metastatic disease who underwent surgical resection with curative intent, the 5-year overall survival rate was 53.3%. The median overall survival for the four patients not treated with curative intent was 17.2 months. \r\n\r\n Conclusions: dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.","Source":"STN","category":"HUMAN","training_data":"Long-Term Survival Among Mismatch Repair Deficient Cholangiocarcinomas Associated With Lynch Syndrome Purpose: Patients with Lynch syndrome (LS) have a significantly elevated lifetime risk of developing biliary tract cancers (BTCs) compared to the general population. However, few studies have characterized the clinical characteristics, genetic features, or long-term outcomes of mismatch-repair deficient (dMMR) cholangiocarcinomas associated with LS. \r\n\r\n Methods: A retrospective review of a prospectively maintained Familial High-Risk GI Cancer Clinic database identified all patients with BTCs evaluated from 2006 to 2016 who carried germline mutations in MLH1, MSH2, MSH6, or PMS2. \r\n\r\n Results: Eleven patients with BTCs were identified: four perihilar, four intrahepatic, one extrahepatic, one gallbladder, and one ampulla of Vater. All patients had underlying germline mutations and a personal history of a LS-associated malignancy, most commonly (63.3%) colorectal cancer. Ten (90.9%) patients were surgically explored, and margin negative resection was possible in seven (63.3%). Chemotherapy (90.9%) and/or chemoradiation (45.5%) was administered to most patients. Among the seven patients presenting with non-metastatic disease who underwent surgical resection with curative intent, the 5-year overall survival rate was 53.3%. The median overall survival for the four patients not treated with curative intent was 17.2 months. \r\n\r\n Conclusions: dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers. STN","prediction_labels":"HUMAN"},{"cleaned":"significance ceacam6 expression biliary tract carcinoma background entire biliary tree risk malignant change little known differences molecular pathogenesis respect anatomic site ceacam6 membrane protein involved cell adhesion signaling overexpressed pancreatic adenocarcinoma associated poor prognosis study examines ceacam6 expression entire spectrum biliary carcinomas relationship outcome methods tissue microarrays containing triplicate cores paraffin embedded surgical specimens patients bile duct carcinoma hilar intrahepatic distal control tissue stained ceacam6 immunohistochemistry clinical pathologic survival data analyzed correlated ceacam6 expression survival estimated using kaplan meier method compared log rank test results one hundred twenty cases bile duct carcinomas 1992 2007 assembled tissue microarrays strong ceacam6 signal present 30 60 50 hilar tumors 7 45 16 intrahepatic tumors 7 15 47 distal tumors none control tissues overall median survival follow 36 4 months 98 3 months respectively ceacam6 staining correlate sex grade positive lymph nodes vascular invasion metastases associated age 65 p 0 05 higher stage p 0 05 r0 resection ceacam6 expression associated disease specific survival dss subset patients intrahepatic cholangiocarcinoma median dss 78 months negative 16 months positive p 0 002 vascular invasion sole independent predictor survival multivariate proportional hazards regression hr 1 742 1 048 2 895 95 ci p 0 03 entire cohort conclusions ceacam6 may serve marker poor outcome patients intrahepatic cholangiocarcinoma evaluated means selecting patients adjuvant therapy resection google scholar","probabilities":0.9467213,"Title":"Significance Of Ceacam6 Expression In Biliary Tract Carcinoma","Abstract":"Background: The entire biliary tree is at risk for malignant change, but little is known about differences in molecular pathogenesis with respect to anatomic site. CEACAM6 is a membrane protein involved in cell adhesion and signaling that is overexpressed in pancreatic adenocarcinoma and associated with poor prognosis. This study examines CEACAM6 expression in the entire spectrum of biliary carcinomas and its relationship to outcome.\nMethods: Tissue microarrays containing triplicate cores of paraffin-embedded surgical specimens from patients with bile duct carcinoma (hilar, intrahepatic, distal) and control tissue were stained for CEACAM6 by immunohistochemistry. Clinical, pathologic and survival data were analyzed and correlated with CEACAM6 expression. Survival was estimated using the Kaplan-Meier method and compared with log rank test.\n\nResults: One hundred twenty cases of bile duct carcinomas from 1992-2007 were assembled in the tissue microarrays. Strong CEACAM6 signal was present in 30/60 (50%) of hilar tumors, 7/45 (16%) of intrahepatic tumors, 7/15 (47%) of distal tumors, and none of the control tissues. Overall median survival and follow-up were 36.4 months and 98.3 months, respectively. CEACAM6 staining did not correlate with sex, grade, positive lymph nodes, vascular invasion or metastases but was associated with age > 65 (p<0.05) and higher T stage (p<0.05). After R0 resection, CEACAM6 expression was associated with disease-specific survival (DSS) only in the subset of patients with intrahepatic cholangiocarcinoma (median DSS 78 months for negative and 16 months for positive, p<0.002). Vascular invasion was the sole independent predictor of survival on multivariate proportional hazards regression (HR=1.742 [1.048-2.895 95%CI], p<0.03) in the entire cohort.\n\nConclusions: CEACAM6 may serve as a marker of poor outcome in patients with intrahepatic cholangiocarcinoma and should be further evaluated as a means of selecting patients for adjuvant therapy after resection.","Source":"Google Scholar","category":"ANIMAL","training_data":"Significance Of Ceacam6 Expression In Biliary Tract Carcinoma Background: The entire biliary tree is at risk for malignant change, but little is known about differences in molecular pathogenesis with respect to anatomic site. CEACAM6 is a membrane protein involved in cell adhesion and signaling that is overexpressed in pancreatic adenocarcinoma and associated with poor prognosis. This study examines CEACAM6 expression in the entire spectrum of biliary carcinomas and its relationship to outcome.\nMethods: Tissue microarrays containing triplicate cores of paraffin-embedded surgical specimens from patients with bile duct carcinoma (hilar, intrahepatic, distal) and control tissue were stained for CEACAM6 by immunohistochemistry. Clinical, pathologic and survival data were analyzed and correlated with CEACAM6 expression. Survival was estimated using the Kaplan-Meier method and compared with log rank test.\n\nResults: One hundred twenty cases of bile duct carcinomas from 1992-2007 were assembled in the tissue microarrays. Strong CEACAM6 signal was present in 30/60 (50%) of hilar tumors, 7/45 (16%) of intrahepatic tumors, 7/15 (47%) of distal tumors, and none of the control tissues. Overall median survival and follow-up were 36.4 months and 98.3 months, respectively. CEACAM6 staining did not correlate with sex, grade, positive lymph nodes, vascular invasion or metastases but was associated with age > 65 (p<0.05) and higher T stage (p<0.05). After R0 resection, CEACAM6 expression was associated with disease-specific survival (DSS) only in the subset of patients with intrahepatic cholangiocarcinoma (median DSS 78 months for negative and 16 months for positive, p<0.002). Vascular invasion was the sole independent predictor of survival on multivariate proportional hazards regression (HR=1.742 [1.048-2.895 95%CI], p<0.03) in the entire cohort.\n\nConclusions: CEACAM6 may serve as a marker of poor outcome in patients with intrahepatic cholangiocarcinoma and should be further evaluated as a means of selecting patients for adjuvant therapy after resection. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"tumorigenic index determine liver cancer initiation prognosis background incidence mortality liver cancer mainly hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc increasing rapidly worldwide unmet effective therapeutic means far consistent complex multifactorial etiologies multi omics analyses human hcc icc samples identi ed vast genomic heterogeneity molecular cellular defects metabolic reprogramming subtypes tumors well altered tumor microenvironment however remains determined common molecular signatures transcriptomes exist liver cancer despite considerable genomic heterogeneity furthermore little known kinetics fashions either gradual accumulation dramatic transition generation cell intrinsic extrinsic signals intertwined drive malignant transformation tumor initiation methods probe stepwise mechanisms hepatocarcinogenesis interrogated temporal gene expression pro les several mouse models hepatic steatosis brosis ammation consequently tumorigenesis integrating pathological examination transcriptomic pro ling bioinformatic analysis mathematic modeling performed quantitative analysis dynamics molecular changes liver transcriptomes pre cancer cancer stages mouse hcc models liver cancer patients diverse etiologies well pre cancer patients chronic liver diseases results instead anticipated gradual changes identi ed sudden transcriptomic switch critical pre cancer stage based analysis transcription factor tf clusters coarse grained network modeling demonstrated abrupt transcriptomic transition occurred changes accumulated reach threshold conclusion de ned tumorigenic index ti quantify tumorigenic signal strengths based multi layer analysis transcriptomes used effectively predict tumor stages prognosis liver cancer patients public datasets work establishes powerful quantitative method risk assessment pre cancer liver disease subjects better triage liver cancer patients diverse backgrounds google scholar","probabilities":0.9467213,"Title":"A Tumorigenic Index To Determine Liver Cancer Initiation And Prognosis","Abstract":"Background: The incidence and mortality of liver cancer, mainly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), are increasing rapidly worldwide, which has been unmet with effective therapeutic means so far. Consistent with the complex and multifactorial etiologies, multi-omics analyses of human HCC and ICC samples have identied vast genomic heterogeneity, molecular and cellular defects, metabolic reprogramming, and subtypes of the tumors as well as the altered tumor microenvironment. However, it remains to be determined if any common molecular signatures in the transcriptomes exist for liver cancer, despite their considerable genomic heterogeneity. Furthermore, little is known about the kinetics and fashions, either gradual accumulation or dramatic transition, in generation of cell-intrinsic and -extrinsic signals that are intertwined to drive malignant transformation and tumor initiation. Methods: To probe the stepwise mechanisms of hepatocarcinogenesis, we interrogated temporal gene expression proles in several mouse models with hepatic steatosis, brosis, inammation and consequently tumorigenesis. By integrating pathological examination, transcriptomic proling, bioinformatic analysis and mathematic modeling, we performed quantitative analysis of the dynamics of molecular changes in liver transcriptomes at pre-cancer and cancer stages, in both mouse HCC models and liver cancer patients with diverse etiologies as well as pre-cancer patients with chronic liver diseases. Results: Instead of anticipated gradual changes, we identied a sudden transcriptomic switch at a critical pre-cancer stage based on analysis of transcription factor (TF) clusters. Coarse-grained network modeling further demonstrated that the abrupt transcriptomic transition occurred once changes were accumulated to reach a threshold. Conclusion: We dened a tumorigenic index (TI) to quantify tumorigenic signal strengths based on a multi-layer analysis of transcriptomes, which could be used to effectively predict tumor stages and prognosis of liver cancer patients in public datasets. This work establishes a powerful quantitative method for risk assessment of pre-cancer liver disease subjects and for better triage of liver cancer patients with diverse backgrounds.","Source":"Google Scholar","category":"ANIMAL","training_data":"A Tumorigenic Index To Determine Liver Cancer Initiation And Prognosis Background: The incidence and mortality of liver cancer, mainly hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), are increasing rapidly worldwide, which has been unmet with effective therapeutic means so far. Consistent with the complex and multifactorial etiologies, multi-omics analyses of human HCC and ICC samples have identied vast genomic heterogeneity, molecular and cellular defects, metabolic reprogramming, and subtypes of the tumors as well as the altered tumor microenvironment. However, it remains to be determined if any common molecular signatures in the transcriptomes exist for liver cancer, despite their considerable genomic heterogeneity. Furthermore, little is known about the kinetics and fashions, either gradual accumulation or dramatic transition, in generation of cell-intrinsic and -extrinsic signals that are intertwined to drive malignant transformation and tumor initiation. Methods: To probe the stepwise mechanisms of hepatocarcinogenesis, we interrogated temporal gene expression proles in several mouse models with hepatic steatosis, brosis, inammation and consequently tumorigenesis. By integrating pathological examination, transcriptomic proling, bioinformatic analysis and mathematic modeling, we performed quantitative analysis of the dynamics of molecular changes in liver transcriptomes at pre-cancer and cancer stages, in both mouse HCC models and liver cancer patients with diverse etiologies as well as pre-cancer patients with chronic liver diseases. Results: Instead of anticipated gradual changes, we identied a sudden transcriptomic switch at a critical pre-cancer stage based on analysis of transcription factor (TF) clusters. Coarse-grained network modeling further demonstrated that the abrupt transcriptomic transition occurred once changes were accumulated to reach a threshold. Conclusion: We dened a tumorigenic index (TI) to quantify tumorigenic signal strengths based on a multi-layer analysis of transcriptomes, which could be used to effectively predict tumor stages and prognosis of liver cancer patients in public datasets. This work establishes a powerful quantitative method for risk assessment of pre-cancer liver disease subjects and for better triage of liver cancer patients with diverse backgrounds. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"resection hilar cholangiocarcinoma analysis prognostic factors impact systemic inflammation long term outcome introduction resection hilar cholangiocarcinoma single hope long term survival methods ninety patients underwent curative intent surgery hilar cholangiocarcinoma 1996 2012 potential prognostic factors assessed univariate kaplan meier curves log rank test multivariate analyses cox proportional hazards model results median overall disease free survivals 26 17 months respectively multivariate analysis identified r0 resection hr 0 03 95 ci 0 0 19 p 0 001 caudate lobe invasion hr 6 33 95 ci 1 31 30 46 p 0 021 adjuvant gemcitabine based chemotherapy hr 0 38 95 ci 0 15 0 94 p 0 037 neutrophil lymphocyte ratio hr 0 78 95 ci 0 62 0 98 p 0 036 independent prognostic factors disease free survival independent prognostic factors overall survival r0 resection hr 0 03 95 ci 0 0 22 p 0 001 caudate lobe invasion hr 11 75 95 ci 1 65 83 33 p 0 014 adjuvant gemcitabine based chemotherapy hr 0 19 95 ci 0 06 0 56 p 0 003 conclusions negative resection margin represents important prognostic factor adjuvant gemcitabine based chemotherapy appears benefit survival neutrophil lymphocyte ratio may potentially used stratify patients future clinical trials pubmed","probabilities":0.9799733,"Title":"Resection for hilar cholangiocarcinoma: analysis of prognostic factors and the impact of systemic inflammation on long-term outcome","Abstract":"INTRODUCTION: Resection for hilar cholangiocarcinoma is the single hope for long-term survival. METHODS: Ninety patients underwent curative intent surgery for hilar cholangiocarcinoma between 1996 and 2012. The potential prognostic factors were assessed by univariate (Kaplan-Meier curves and log-rank test) and multivariate analyses (Cox proportional hazards model). RESULTS: The median overall and disease-free survivals were 26 and 17 months, respectively. The multivariate analysis identified R0 resection (HR = 0.03, 95 % CI 0-0.19, p < 0.001), caudate lobe invasion (HR = 6.33, 95 % CI 1.31-30.46, p = 0.021), adjuvant gemcitabine-based chemotherapy (HR = 0.38, 95 % CI 0.15-0.94, p = 0.037), and the neutrophil-to-lymphocyte ratio (HR = 0.78, 95 % CI 0.62-0.98, p = 0.036) as independent prognostic factors for disease-free survival. The independent prognostic factors for overall survival were R0 resection (HR = 0.03, 95 % CI 0-0.22, p < 0.001), caudate lobe invasion (HR = 11.75, 95 % CI 1.65-83.33, p = 0.014), and adjuvant gemcitabine-based chemotherapy (HR = 0.19, 95 % CI 0.06-0.56, p = 0.003). CONCLUSIONS: The negative resection margin represents the most important prognostic factor. Adjuvant gemcitabine-based chemotherapy appears to benefit survival. The neutrophil-to-lymphocyte ratio may potentially be used to stratify patients for future clinical trials.","Source":"PubMed","category":"HUMAN","training_data":"Resection for hilar cholangiocarcinoma: analysis of prognostic factors and the impact of systemic inflammation on long-term outcome INTRODUCTION: Resection for hilar cholangiocarcinoma is the single hope for long-term survival. METHODS: Ninety patients underwent curative intent surgery for hilar cholangiocarcinoma between 1996 and 2012. The potential prognostic factors were assessed by univariate (Kaplan-Meier curves and log-rank test) and multivariate analyses (Cox proportional hazards model). RESULTS: The median overall and disease-free survivals were 26 and 17 months, respectively. The multivariate analysis identified R0 resection (HR = 0.03, 95 % CI 0-0.19, p < 0.001), caudate lobe invasion (HR = 6.33, 95 % CI 1.31-30.46, p = 0.021), adjuvant gemcitabine-based chemotherapy (HR = 0.38, 95 % CI 0.15-0.94, p = 0.037), and the neutrophil-to-lymphocyte ratio (HR = 0.78, 95 % CI 0.62-0.98, p = 0.036) as independent prognostic factors for disease-free survival. The independent prognostic factors for overall survival were R0 resection (HR = 0.03, 95 % CI 0-0.22, p < 0.001), caudate lobe invasion (HR = 11.75, 95 % CI 1.65-83.33, p = 0.014), and adjuvant gemcitabine-based chemotherapy (HR = 0.19, 95 % CI 0.06-0.56, p = 0.003). CONCLUSIONS: The negative resection margin represents the most important prognostic factor. Adjuvant gemcitabine-based chemotherapy appears to benefit survival. The neutrophil-to-lymphocyte ratio may potentially be used to stratify patients for future clinical trials. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder cancer cholecystectomy 1990 2014 introduction cancer gallbladder serious diagnostic therapeutic problem according literature 30 cases confirmed surgery cases detected incidentally histopathology clinical trials meta analyses show incidental gallbladder cancer igbc occurs 0 19 2 8 patients cholecystectomy aim study analyze incidence severity igbc cholecystectomy procedures performed surgical department 4th military teaching hospital wroclaw years 1990 2014 patients methods years 1990 2014 total 7 314 cholecystectomies performed surgical department cholecystolithiasis 6 145 performed using laparoscopic approach 84 02 867 performed open surgery 11 8 302 cases required conversion 5 1 group 5 214 patients females 71 3 2 100 males 28 7 average age 54 7 years results found 64 igbc cases confirmed histopathology represented 0 87 cases group 50 patients females 78 1 14 males 21 8 average age 67 1 years group 40 patients underwent classic cholecystectomy 24 underwent laparoscopic procedures 13 cases ultimately required traditional surgery histopathology showed 15 carcinomas classified g1 23 4 28 g2 43 75 21 g3 32 8 conclusion igbc detected cholecystectomy due cholecystolithiasis rare disease found igbc 0 87 cases comparable scale world literature case cancer frequently found necessary convert open surgical procedure cancer common females people 60 years age stn","probabilities":0.9799733,"Title":"Incidental Gallbladder Cancer After Cholecystectomy: 1990 To 2014","Abstract":"Introduction: Cancer of the gallbladder is a serious diagnostic and therapeutic problem. According to the literature, 30% of cases are not confirmed before surgery. Other cases are detected incidentally by histopathology. Clinical trials and meta-analyses show that incidental gallbladder cancer (iGBC) occurs in 0.19%-2.8% of patients after cholecystectomy. The aim of this study was to analyze the incidence and severity of iGBC in cholecystectomy procedures performed in the surgical department at the 4th Military Teaching Hospital in Wroclaw during the years 1990-2014. \r\n\r\n Patients and methods: In the years 1990-2014, a total of 7,314 cholecystectomies were performed in the surgical department because of cholecystolithiasis: 6,145 were performed using the laparoscopic approach (84.02%), 867 were performed as open surgery (11.8%), and 302 cases required conversion (5.1%). In this group, 5,214 of the patients were females (71.3%) and 2,100 were males (28.7%), with an average age of 54.7 years. \r\n\r\n Results: We found 64 iGBC cases which were confirmed by histopathology. This represented 0.87% of all cases. In this group, 50 patients were females (78.1%) and 14 were males (21.8%), with an average age of 67.1 years. Of this group, 40 patients underwent a classic cholecystectomy, while 24 underwent laparoscopic procedures, out of which 13 cases ultimately required traditional surgery. The histopathology showed 15 carcinomas that were classified as G1 (23.4%), 28 were G2 (43.75%), and 21 were G3 (32.8%). \r\n\r\n Conclusion: iGBC detected after a cholecystectomy due to cholecystolithiasis is a rare disease. We found iGBC in 0.87% of cases, which is on a comparable scale to the world literature. In the case of cancer, we frequently found it necessary to convert to an open surgical procedure. This cancer is more common in females and in people over 60 years of age.","Source":"STN","category":"HUMAN","training_data":"Incidental Gallbladder Cancer After Cholecystectomy: 1990 To 2014 Introduction: Cancer of the gallbladder is a serious diagnostic and therapeutic problem. According to the literature, 30% of cases are not confirmed before surgery. Other cases are detected incidentally by histopathology. Clinical trials and meta-analyses show that incidental gallbladder cancer (iGBC) occurs in 0.19%-2.8% of patients after cholecystectomy. The aim of this study was to analyze the incidence and severity of iGBC in cholecystectomy procedures performed in the surgical department at the 4th Military Teaching Hospital in Wroclaw during the years 1990-2014. \r\n\r\n Patients and methods: In the years 1990-2014, a total of 7,314 cholecystectomies were performed in the surgical department because of cholecystolithiasis: 6,145 were performed using the laparoscopic approach (84.02%), 867 were performed as open surgery (11.8%), and 302 cases required conversion (5.1%). In this group, 5,214 of the patients were females (71.3%) and 2,100 were males (28.7%), with an average age of 54.7 years. \r\n\r\n Results: We found 64 iGBC cases which were confirmed by histopathology. This represented 0.87% of all cases. In this group, 50 patients were females (78.1%) and 14 were males (21.8%), with an average age of 67.1 years. Of this group, 40 patients underwent a classic cholecystectomy, while 24 underwent laparoscopic procedures, out of which 13 cases ultimately required traditional surgery. The histopathology showed 15 carcinomas that were classified as G1 (23.4%), 28 were G2 (43.75%), and 21 were G3 (32.8%). \r\n\r\n Conclusion: iGBC detected after a cholecystectomy due to cholecystolithiasis is a rare disease. We found iGBC in 0.87% of cases, which is on a comparable scale to the world literature. In the case of cancer, we frequently found it necessary to convert to an open surgical procedure. This cancer is more common in females and in people over 60 years of age. STN","prediction_labels":"HUMAN"},{"cleaned":"expression p53 upregulated modulator apoptosis puma c myb gallbladder adenocarcinoma pathological significance purpose increasing number studies shown puma c myb signaling pathways involved various human cancers including colon carcinomas however studies examined gallbladder cancer specimens little known clinical pathological significance signaling changes may gallbladder adenocarcinoma study investigated expression puma c myb benign malignant lesions gallbladder pathological significance methods tissue specimens 108 gallbladder adenocarcinoma patients 46 adjacent tissues 15 cases adenomatous polyps 35 surgical specimens chronic cholecystitis patients routinely paraffin embedded sectioned puma c myb expressions detected envision immunohistochemistry results positive rates puma c myb significantly higher gallbladder adenocarcinoma tissues three p 0 01 gallbladder epithelial cells puma c myb positive benign cases manifest moderate severe atypical dysplasia positive rates puma c myb well differentiated tumors maximum diameter 2 cm lymph node metastasis invasion surrounding tissues significantly lower poorly differentiated cases maximum diameter 2 cm lymph node metastasis invasion surrounding tissues p 0 05 p 0 01 postoperative survival patients whose tumor specimens positive puma c myb significantly shorter negative markers p 0 05 p 0 01 conclusions results demonstrated puma c myb positive gallbladder tumors progress rapidly prone metastasis possess strong invasive ability poor prognosis pubmed","probabilities":0.8684211,"Title":"Expression of p53 upregulated modulator of apoptosis (PUMA) and C-myb in gallbladder adenocarcinoma and their pathological significance","Abstract":"PURPOSE: An increasing number of studies have shown that PUMA and C-myb signaling pathways are involved in various human cancers including colon carcinomas. However, few studies have examined gallbladder cancer specimens, and little is known about the clinical and pathological significance signaling changes may have in gallbladder adenocarcinoma. This study has investigated the expression of PUMA and C-myb in benign and malignant lesions of gallbladder and its pathological significance. METHODS: Tissue specimens from 108 gallbladder adenocarcinoma patients, 46 adjacent tissues, 15 cases of adenomatous polyps, and 35 surgical specimens from chronic cholecystitis patients were routinely paraffin embedded and sectioned. PUMA and C-myb expressions were detected with EnVision immunohistochemistry. RESULTS: Positive rates of PUMA and C-myb are significantly higher in gallbladder adenocarcinoma tissues than that in the other three (P < 0.01). Gallbladder epithelial cells in PUMA and/or C-myb positive benign cases manifest moderate to severe atypical dysplasia. Positive rates of PUMA and C-myb in well-differentiated tumors with maximum diameter of <2 cm and with no lymph node metastasis and invasion of the surrounding tissues are significantly lower than that in those poorly differentiated cases with maximum diameter of ≥ 2 cm, lymph node metastasis, and invasion of the surrounding tissues (P < 0.05 or P < 0.01). The postoperative survival of patients whose tumor specimens are positive for PUMA and C-myb is significantly shorter than that of those who are negative for both markers (P < 0.05 or P < 0.01). CONCLUSIONS: Our results have demonstrated that PUMA and C-myb positive gallbladder tumors progress rapidly, are prone to metastasis, possess strong invasive ability, and have poor prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Expression of p53 upregulated modulator of apoptosis (PUMA) and C-myb in gallbladder adenocarcinoma and their pathological significance PURPOSE: An increasing number of studies have shown that PUMA and C-myb signaling pathways are involved in various human cancers including colon carcinomas. However, few studies have examined gallbladder cancer specimens, and little is known about the clinical and pathological significance signaling changes may have in gallbladder adenocarcinoma. This study has investigated the expression of PUMA and C-myb in benign and malignant lesions of gallbladder and its pathological significance. METHODS: Tissue specimens from 108 gallbladder adenocarcinoma patients, 46 adjacent tissues, 15 cases of adenomatous polyps, and 35 surgical specimens from chronic cholecystitis patients were routinely paraffin embedded and sectioned. PUMA and C-myb expressions were detected with EnVision immunohistochemistry. RESULTS: Positive rates of PUMA and C-myb are significantly higher in gallbladder adenocarcinoma tissues than that in the other three (P < 0.01). Gallbladder epithelial cells in PUMA and/or C-myb positive benign cases manifest moderate to severe atypical dysplasia. Positive rates of PUMA and C-myb in well-differentiated tumors with maximum diameter of <2 cm and with no lymph node metastasis and invasion of the surrounding tissues are significantly lower than that in those poorly differentiated cases with maximum diameter of ≥ 2 cm, lymph node metastasis, and invasion of the surrounding tissues (P < 0.05 or P < 0.01). The postoperative survival of patients whose tumor specimens are positive for PUMA and C-myb is significantly shorter than that of those who are negative for both markers (P < 0.05 or P < 0.01). CONCLUSIONS: Our results have demonstrated that PUMA and C-myb positive gallbladder tumors progress rapidly, are prone to metastasis, possess strong invasive ability, and have poor prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"molecular profiling stroma identifies osteopontin independent predictor poor prognosis intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc second common type primary cancer liver icc aggressive cancer poor prognosis limited therapeutic strategies identification new drug targets prognostic biomarkers important clinical challenge icc presence abundant stroma histological hallmark icc given well established role stromal compartment progression cancer diseases hypothesized relevant biomarkers identified analyzing stroma icc combining laser capture microdissection gene expression profiling demonstrate icc stromal cells exhibit dramatic genomic changes identified signature 1 073 nonredundant genes significantly discriminate tumor stroma nontumor fibrous tissue functional analysis differentially expressed genes demonstrated regulated genes stroma icc related cell cycle extracellular matrix transforming growth factor beta tgf pathways tissue microarray analysis using independent cohort 40 icc patients validated protein level increased expression collagen 4a1 col4a1 laminin gamma 2 lamc2 osteopontin spp1 kiaa0101 tgf 2 genes stroma icc statistical analysis clinical pathological features demonstrated expression osteopontin tgf 2 laminin stroma icc significantly correlated overall patient survival important multivariate analysis demonstrated stromal expression osteopontin independent prognostic marker overall disease free survival conclusion study identifies clinically relevant genomic alterations stroma icc including candidate biomarkers prognosis supporting idea tumor stroma important factor icc onset progression pubmed","probabilities":0.962963,"Title":"Molecular profiling of stroma identifies osteopontin as an independent predictor of poor prognosis in intrahepatic cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary cancer in the liver. ICC is an aggressive cancer with poor prognosis and limited therapeutic strategies. The identification of new drug targets and prognostic biomarkers is an important clinical challenge for ICC. The presence of an abundant stroma is a histological hallmark of ICC. Given the well-established role of the stromal compartment in the progression of cancer diseases, we hypothesized that relevant biomarkers could be identified by analyzing the stroma of ICC. By combining laser capture microdissection and gene expression profiling, we demonstrate that ICC stromal cells exhibit dramatic genomic changes. We identified a signature of 1,073 nonredundant genes that significantly discriminate the tumor stroma from nontumor fibrous tissue. Functional analysis of differentially expressed genes demonstrated that up-regulated genes in the stroma of ICC were related to cell cycle, extracellular matrix, and transforming growth factor beta (TGFβ) pathways. Tissue microarray analysis using an independent cohort of 40 ICC patients validated at a protein level the increased expression of collagen 4A1/COL4A1, laminin gamma 2/LAMC2, osteopontin/SPP1, KIAA0101, and TGFβ2 genes in the stroma of ICC. Statistical analysis of clinical and pathological features demonstrated that the expression of osteopontin, TGFβ2, and laminin in the stroma of ICC was significantly correlated with overall patient survival. More important, multivariate analysis demonstrated that the stromal expression of osteopontin was an independent prognostic marker for overall and disease-free survival. CONCLUSION: The study identifies clinically relevant genomic alterations in the stroma of ICC, including candidate biomarkers for prognosis, supporting the idea that tumor stroma is an important factor for ICC onset and progression.","Source":"PubMed","category":"HUMAN","training_data":"Molecular profiling of stroma identifies osteopontin as an independent predictor of poor prognosis in intrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary cancer in the liver. ICC is an aggressive cancer with poor prognosis and limited therapeutic strategies. The identification of new drug targets and prognostic biomarkers is an important clinical challenge for ICC. The presence of an abundant stroma is a histological hallmark of ICC. Given the well-established role of the stromal compartment in the progression of cancer diseases, we hypothesized that relevant biomarkers could be identified by analyzing the stroma of ICC. By combining laser capture microdissection and gene expression profiling, we demonstrate that ICC stromal cells exhibit dramatic genomic changes. We identified a signature of 1,073 nonredundant genes that significantly discriminate the tumor stroma from nontumor fibrous tissue. Functional analysis of differentially expressed genes demonstrated that up-regulated genes in the stroma of ICC were related to cell cycle, extracellular matrix, and transforming growth factor beta (TGFβ) pathways. Tissue microarray analysis using an independent cohort of 40 ICC patients validated at a protein level the increased expression of collagen 4A1/COL4A1, laminin gamma 2/LAMC2, osteopontin/SPP1, KIAA0101, and TGFβ2 genes in the stroma of ICC. Statistical analysis of clinical and pathological features demonstrated that the expression of osteopontin, TGFβ2, and laminin in the stroma of ICC was significantly correlated with overall patient survival. More important, multivariate analysis demonstrated that the stromal expression of osteopontin was an independent prognostic marker for overall and disease-free survival. CONCLUSION: The study identifies clinically relevant genomic alterations in the stroma of ICC, including candidate biomarkers for prognosis, supporting the idea that tumor stroma is an important factor for ICC onset and progression. PubMed","prediction_labels":"HUMAN"},{"cleaned":"high expression matrix metalloproteinase 11 indicates poor prognosis human cholangiocarcinoma background cholangiocarcinoma chca serious public health problem thailand especially northeastern northern regions chca known one aggressive malignant tumors associated local invasion high rate metastasis crucial step invasion process proteolytic degradation extracellular matrix ecm basal membranes several studies shown critical role played matrix metalloproteinase 11 mmp 11 objective study aim detect mmp 11 expression chca specimens correlation survival time materials methods retrospective analysis conducted 30 patients chca rajvithi hospital undergone immunohistochemical staining mmp 11 relationships clinicopathological data mmp 11 expression chca specimens analyzed 2 test fisher exact test estimated survival survival differences analyzed kaplan meier method log rank test respectively results mmp 11 expression found 15 specimens 50 overall mean survival time 237 0 days 95 ci 135 4 338 5 sd 271 9 specimens positive mmp 11 average survival time 136 7 days 95 ci 50 3 223 1 sd 156 0 survival differences signficant positive negative mmp 11 p 0 022 well differentiated tumor moderate poor differentiated tumor p 0 755 ca19 9 level 1 000 1 000 p 0 488 advanced non advanced staging p 0 388 conclusions positive mmp 11 expression indicates poor prognosis chca specimens pubmed","probabilities":0.8684211,"Title":"High Expression of Matrix Metalloproteinase-11 indicates Poor Prognosis in Human Cholangiocarcinoma","Abstract":"BACKGROUND: Cholangiocarcinoma (CHCA) is serious public health problem in Thailand, especially in the northeastern and northern regions. CHCA is known as one of the most aggressive malignant tumors associated with local invasion and a high rate of metastasis. A crucial step in the invasion process is the proteolytic degradation of the extracellular matrix (ECM) and basal membranes, for which several studies have shown a critical role played by matrix metalloproteinase-11 (MMP-11). OBJECTIVE: This study aim to detect MMP-11 expression in CHCA specimens and any correlation with survival time. MATERIALS AND METHODS: A retrospective analysis was conducted of 30 patients with CHCA in Rajvithi hospital, who had undergone immunohistochemical staining of MMP-11. Relationships between clinicopathological data and MMP-11 expression in CHCA specimens were analyzed by the χ2 test or Fisher's exact test. The estimated survival and the survival differences were analyzed by the Kaplan-Meier method and the log-rank test, respectively. RESULTS: MMP-11 expression was found in 15 specimens (50%). The overall mean survival time is 237.0 days (95% CI 135.4-338.5, SD 271.9). Specimens with a positive MMP-11 had an average survival time of 136.7 days (95%CI 50.3-223.1, SD 156.0). Survival differences was signficant for the positive and negative MMP-11(p=0.022), but not well differentiated tumor and moderate to poor differentiated tumor (p=0.755), CA19-9 level of >1,000 and <1,000 (p=0.488), and between advanced and non-advanced staging (p=0.388). CONCLUSIONS: The positive MMP-11 expression indicates poor prognosis in CHCA specimens.","Source":"PubMed","category":"ANIMAL","training_data":"High Expression of Matrix Metalloproteinase-11 indicates Poor Prognosis in Human Cholangiocarcinoma BACKGROUND: Cholangiocarcinoma (CHCA) is serious public health problem in Thailand, especially in the northeastern and northern regions. CHCA is known as one of the most aggressive malignant tumors associated with local invasion and a high rate of metastasis. A crucial step in the invasion process is the proteolytic degradation of the extracellular matrix (ECM) and basal membranes, for which several studies have shown a critical role played by matrix metalloproteinase-11 (MMP-11). OBJECTIVE: This study aim to detect MMP-11 expression in CHCA specimens and any correlation with survival time. MATERIALS AND METHODS: A retrospective analysis was conducted of 30 patients with CHCA in Rajvithi hospital, who had undergone immunohistochemical staining of MMP-11. Relationships between clinicopathological data and MMP-11 expression in CHCA specimens were analyzed by the χ2 test or Fisher's exact test. The estimated survival and the survival differences were analyzed by the Kaplan-Meier method and the log-rank test, respectively. RESULTS: MMP-11 expression was found in 15 specimens (50%). The overall mean survival time is 237.0 days (95% CI 135.4-338.5, SD 271.9). Specimens with a positive MMP-11 had an average survival time of 136.7 days (95%CI 50.3-223.1, SD 156.0). Survival differences was signficant for the positive and negative MMP-11(p=0.022), but not well differentiated tumor and moderate to poor differentiated tumor (p=0.755), CA19-9 level of >1,000 and <1,000 (p=0.488), and between advanced and non-advanced staging (p=0.388). CONCLUSIONS: The positive MMP-11 expression indicates poor prognosis in CHCA specimens. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prevalence bile duct cancer among printing industry workers comparison industries objectives aim study assess risk developing bile duct cancer among workers printing industry comparison workers industries general methods prevalence bile duct cancer compared workers printing industry age standardized controls industries using claims database japan health insurance association insures workers small medium sized employers industries results young aged 30 49 male workers printing industry showed elevated insignificant standardized prevalence rate ratio sprr bile duct cancer comparison workers industries sprr 1 78 95 ci 0 63 5 00 risk higher intrahepatic bile duct cancer remained insignificant sprr 3 03 95 ci 0 52 17 56 conclusions sharply elevated risk bile duct cancer observed among proof printing workers printing factory osaka may generalizable workers printing industry nationwide stn","probabilities":0.9799733,"Title":"Prevalence Of Bile Duct Cancer Among Printing Industry Workers In Comparison With Other Industries","Abstract":"Objectives: The aim of this study was to assess the risk of developing bile duct cancer among workers in the other printing industry in comparison with workers in all industries in general. \r\n\r\n Methods: Prevalence of bile duct cancer was compared between workers in the printing industry and age-standardized controls in all other industries using the claims database of the Japan Health Insurance Association, which insures workers of small-medium sized employers of all industries. \r\n\r\n Results: Young (aged 30-49) male workers in the printing industry showed an elevated but insignificant standardized prevalence rate ratio (SPRR) for bile duct cancer in comparison with workers in all other industries (SPRR: 1.78; 95%CI: 0.63-5.00). The risk was higher for intrahepatic bile duct cancer but remained insignificant (SPRR: 3.03; 95%CI: 0.52-17.56). \r\n\r\n Conclusions: The sharply elevated risk of bile duct cancer observed among proof-printing workers of a printing factory in Osaka may not be generalizable to workers in the printing industry nationwide.","Source":"STN","category":"HUMAN","training_data":"Prevalence Of Bile Duct Cancer Among Printing Industry Workers In Comparison With Other Industries Objectives: The aim of this study was to assess the risk of developing bile duct cancer among workers in the other printing industry in comparison with workers in all industries in general. \r\n\r\n Methods: Prevalence of bile duct cancer was compared between workers in the printing industry and age-standardized controls in all other industries using the claims database of the Japan Health Insurance Association, which insures workers of small-medium sized employers of all industries. \r\n\r\n Results: Young (aged 30-49) male workers in the printing industry showed an elevated but insignificant standardized prevalence rate ratio (SPRR) for bile duct cancer in comparison with workers in all other industries (SPRR: 1.78; 95%CI: 0.63-5.00). The risk was higher for intrahepatic bile duct cancer but remained insignificant (SPRR: 3.03; 95%CI: 0.52-17.56). \r\n\r\n Conclusions: The sharply elevated risk of bile duct cancer observed among proof-printing workers of a printing factory in Osaka may not be generalizable to workers in the printing industry nationwide. STN","prediction_labels":"HUMAN"},{"cleaned":"cg200745 hdac inhibitor induces anti tumour effects cholangiocarcinoma cell lines via mirnas targeting hippo pathway cholangiocarcinoma devastating malignancy fatal complications exhibits low response resistance chemotherapy evaluated anticancer effects cg200745 novel histone deacetylase inhibitor either alone combination standard chemotherapy drugs cholangiocarcinoma cells cg200745 dose dependently reduced viability cholangiocarcinoma cells vitro decreased tumour volume weight xenograft model administering cg200745 along chemotherapeutic agents including gemcitabine 5 fluorouracil 5 fu cisplatin oxaliplatin gemcitabine plus cisplatin decreased cholangiocarcinoma cell viability combination index 1 indicated synergistic action cg200745 also enhanced sensitivity gemcitabine resistant cells gemcitabine 5 fu thereby decreasing cell viability inducing apoptosis accompanied downregulation yap tead4 tgf 2 smad3 notch3 hes5 axl gas6 upregulation mirnas mir 22 3p mir 22 5p mir 194 5p mir 194 3p mir 194 5p mir 210 3p mir 509 3p ingenuity pathway analysis revealed cg200745 mainly targets hippo signalling pathway inducing mir 509 3p expression thus cg200745 inhibits cholangiocarcinoma growth vitro vivo acts synergistically administered combination standard chemotherapeutic agents enabling dose reduction cg200745 therefore expected improve outcome cholangiocarcinoma patients exhibit resistance conventional therapies stn","probabilities":0.9467213,"Title":"Cg200745 An Hdac Inhibitor Induces Anti-Tumour Effects In Cholangiocarcinoma Cell Lines Via Mirnas Targeting The Hippo Pathway","Abstract":"Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action. CG200745 also enhanced the sensitivity of gemcitabine-resistant cells to gemcitabine and 5-FU, thereby decreasing cell viability and inducing apoptosis. This was accompanied by downregulation of YAP, TEAD4, TGF-β2, SMAD3, NOTCH3, HES5, Axl, and Gas6 and upregulation of the miRNAs miR-22-3p, miR-22-5p, miR-194-5p, miR-194-3p, miR-194-5p, miR-210-3p, and miR-509-3p. The Ingenuity Pathway Analysis revealed that CG200745 mainly targets the Hippo signalling pathway by inducing miR-509-3p expression. Thus, CG200745 inhibits cholangiocarcinoma growth in vitro and in vivo, and acts synergistically when administered in combination with standard chemotherapeutic agents, enabling dose reduction. CG200745 is therefore expected to improve the outcome of cholangiocarcinoma patients who exhibit resistance to conventional therapies.","Source":"STN","category":"ANIMAL","training_data":"Cg200745 An Hdac Inhibitor Induces Anti-Tumour Effects In Cholangiocarcinoma Cell Lines Via Mirnas Targeting The Hippo Pathway Cholangiocarcinoma is a devastating malignancy with fatal complications that exhibits low response and resistance to chemotherapy. Here, we evaluated the anticancer effects of CG200745, a novel histone deacetylase inhibitor, either alone or in combination with standard chemotherapy drugs in cholangiocarcinoma cells. CG200745 dose-dependently reduced the viability of cholangiocarcinoma cells in vitro and decreased tumour volume and weight in a xenograft model. Administering CG200745 along with other chemotherapeutic agents including gemcitabine, 5-fluorouracil (5-FU), cisplatin, oxaliplatin, or gemcitabine plus cisplatin further decreased cholangiocarcinoma cell viability, with a combination index < 1 that indicated synergistic action. CG200745 also enhanced the sensitivity of gemcitabine-resistant cells to gemcitabine and 5-FU, thereby decreasing cell viability and inducing apoptosis. This was accompanied by downregulation of YAP, TEAD4, TGF-β2, SMAD3, NOTCH3, HES5, Axl, and Gas6 and upregulation of the miRNAs miR-22-3p, miR-22-5p, miR-194-5p, miR-194-3p, miR-194-5p, miR-210-3p, and miR-509-3p. The Ingenuity Pathway Analysis revealed that CG200745 mainly targets the Hippo signalling pathway by inducing miR-509-3p expression. Thus, CG200745 inhibits cholangiocarcinoma growth in vitro and in vivo, and acts synergistically when administered in combination with standard chemotherapeutic agents, enabling dose reduction. CG200745 is therefore expected to improve the outcome of cholangiocarcinoma patients who exhibit resistance to conventional therapies. STN","prediction_labels":"ANIMAL"},{"cleaned":"irreversible pan inhibitor pf00299804 alone combined gemcitabine antitumor effect biliary tract cancer cell lines biliary tract cancer btc associated poor survival unresponsiveness chemotherapy targeted therapies btc studied family members promising therapeutic targets btc study evaluated efficacy pf00299804 irreversible pan inhibitor eight btc cell lines alone combined gemcitabine pf00299804 potently inhibited growth two cell lines snu308 snu478 eight btc cell lines single agent pf00299804 blocked family downstream signaling pathways inducing g1 arrest apoptosis moreover pf00299804 exerted synergistic effects gemcitabine seven eight btc cell lines possibly regulation genes involved response gemcitabine ts thymidylate synthase rrm1 ribonucleotide reductase mageh1 negatively correlated gemcitabine sensitivity results support need study pf00299804 alone combined gemcitabine treatment btc stn","probabilities":0.9467213,"Title":"The Irreversible Pan-Her Inhibitor Pf00299804 Alone Or Combined With Gemcitabine Has An Antitumor Effect In Biliary Tract Cancer Cell Lines","Abstract":"Biliary tract cancer (BTC) is associated with poor survival and unresponsiveness to chemotherapy. Targeted therapies for BTC have been studied, and HER family members are promising therapeutic targets in BTC. In this study, we evaluated the efficacy of PF00299804, an irreversible pan-HER inhibitor, in eight BTC cell lines alone or combined with gemcitabine. PF00299804 potently inhibited the growth of two cell lines (SNU308 and SNU478) out of the eight BTC cell lines as a single agent. PF00299804 blocked HER family and downstream signaling pathways, inducing G1 arrest or apoptosis. Moreover, PF00299804 exerted synergistic effects with gemcitabine in seven of the eight BTC cell lines, possibly through the regulation of the genes involved in the response to gemcitabine, such as TS (thymidylate synthase), RRM1 (ribonucleotide reductase), and MAGEH1, which is negatively correlated with gemcitabine sensitivity. Our results support the need for further study of PF00299804 alone or combined with gemcitabine for the treatment of BTC.","Source":"STN","category":"ANIMAL","training_data":"The Irreversible Pan-Her Inhibitor Pf00299804 Alone Or Combined With Gemcitabine Has An Antitumor Effect In Biliary Tract Cancer Cell Lines Biliary tract cancer (BTC) is associated with poor survival and unresponsiveness to chemotherapy. Targeted therapies for BTC have been studied, and HER family members are promising therapeutic targets in BTC. In this study, we evaluated the efficacy of PF00299804, an irreversible pan-HER inhibitor, in eight BTC cell lines alone or combined with gemcitabine. PF00299804 potently inhibited the growth of two cell lines (SNU308 and SNU478) out of the eight BTC cell lines as a single agent. PF00299804 blocked HER family and downstream signaling pathways, inducing G1 arrest or apoptosis. Moreover, PF00299804 exerted synergistic effects with gemcitabine in seven of the eight BTC cell lines, possibly through the regulation of the genes involved in the response to gemcitabine, such as TS (thymidylate synthase), RRM1 (ribonucleotide reductase), and MAGEH1, which is negatively correlated with gemcitabine sensitivity. Our results support the need for further study of PF00299804 alone or combined with gemcitabine for the treatment of BTC. STN","prediction_labels":"ANIMAL"},{"cleaned":"body mass index risk 22 specific cancers population based cohort study 5 24 million uk adults background high body mass index bmi predisposes several site specific cancers large scale systematic detailed characterisation patterns risk across common cancers adjusted potential confounders previously undertaken aimed investigate links bmi common site specific cancers methods primary care data individuals clinical practice research datalink bmi data fitted cox models investigate associations bmi 22 common cancers adjusting potential confounders fitted linear non linear spline models investigated effect modification sex menopausal status smoking age calculated population effects findings 5 24 million individuals included 166 955 developed cancers interest bmi associated 17 22 cancers effects varied substantially site 5 kg m 2 increase bmi roughly linearly associated cancers uterus hazard ratio hr 1 62 99 ci 1 56 1 69 p 0 0001 gallbladder 1 31 1 12 1 52 p 0 0001 kidney 1 25 1 17 1 33 p 0 0001 cervix 1 10 1 03 1 17 p 0 00035 thyroid 1 09 1 00 1 19 p 0 0088 leukaemia 1 09 1 05 1 13 p 0 0001 bmi positively associated liver 1 19 1 12 1 27 colon 1 10 1 07 1 13 ovarian 1 09 1 04 1 14 postmenopausal breast cancers 1 05 1 03 1 07 overall p 0 0001 effects varied underlying bmi individual level characteristics estimated inverse associations prostate premenopausal breast cancer risk overall prostate 0 98 0 95 1 00 premenopausal breast cancer 0 89 0 86 0 92 never smokers prostate 0 96 0 93 0 99 premenopausal breast cancer 0 89 0 85 0 94 contrast lung oral cavity cancer observed association never smokers lung 0 99 0 93 1 05 oral cavity 1 07 0 91 1 26 inverse associations overall driven current smokers ex smokers probably residual confounding smoking amount assuming causality 41 uterine 10 gallbladder kidney liver colon cancers attributable excess weight estimated 1 kg m 2 population wide increase bmi result 3790 additional annual uk patients developing one ten cancers positively associated bmi interpretation bmi associated cancer risk substantial population level effects heterogeneity effects suggests different mechanisms associated different cancer sites different patient subgroups funding national institute health research wellcome trust medical research council pubmed","probabilities":0.9799733,"Title":"Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults","Abstract":"BACKGROUND: High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS: With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS: 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION: BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING: National Institute for Health Research, Wellcome Trust, and Medical Research Council.","Source":"PubMed","category":"HUMAN","training_data":"Body-mass index and risk of 22 specific cancers: a population-based cohort study of 5·24 million UK adults BACKGROUND: High body-mass index (BMI) predisposes to several site-specific cancers, but a large-scale systematic and detailed characterisation of patterns of risk across all common cancers adjusted for potential confounders has not previously been undertaken. We aimed to investigate the links between BMI and the most common site-specific cancers. METHODS: With primary care data from individuals in the Clinical Practice Research Datalink with BMI data, we fitted Cox models to investigate associations between BMI and 22 of the most common cancers, adjusting for potential confounders. We fitted linear then non-linear (spline) models; investigated effect modification by sex, menopausal status, smoking, and age; and calculated population effects. FINDINGS: 5·24 million individuals were included; 166,955 developed cancers of interest. BMI was associated with 17 of 22 cancers, but effects varied substantially by site. Each 5 kg/m(2) increase in BMI was roughly linearly associated with cancers of the uterus (hazard ratio [HR] 1·62, 99% CI 1·56-1·69; p<0·0001), gallbladder (1·31, 1·12-1·52; p<0·0001), kidney (1·25, 1·17-1·33; p<0·0001), cervix (1·10, 1·03-1·17; p=0·00035), thyroid (1·09, 1·00-1·19; p=0·0088), and leukaemia (1·09, 1·05-1·13; p≤0·0001). BMI was positively associated with liver (1·19, 1·12-1·27), colon (1·10, 1·07-1·13), ovarian (1·09, 1.04-1.14), and postmenopausal breast cancers (1·05, 1·03-1·07) overall (all p<0·0001), but these effects varied by underlying BMI or individual-level characteristics. We estimated inverse associations with prostate and premenopausal breast cancer risk, both overall (prostate 0·98, 0·95-1·00; premenopausal breast cancer 0·89, 0·86-0·92) and in never-smokers (prostate 0·96, 0·93-0·99; premenopausal breast cancer 0·89, 0·85-0·94). By contrast, for lung and oral cavity cancer, we observed no association in never smokers (lung 0·99, 0·93-1·05; oral cavity 1·07, 0·91-1·26): inverse associations overall were driven by current smokers and ex-smokers, probably because of residual confounding by smoking amount. Assuming causality, 41% of uterine and 10% or more of gallbladder, kidney, liver, and colon cancers could be attributable to excess weight. We estimated that a 1 kg/m(2) population-wide increase in BMI would result in 3790 additional annual UK patients developing one of the ten cancers positively associated with BMI. INTERPRETATION: BMI is associated with cancer risk, with substantial population-level effects. The heterogeneity in the effects suggests that different mechanisms are associated with different cancer sites and different patient subgroups. FUNDING: National Institute for Health Research, Wellcome Trust, and Medical Research Council. PubMed","prediction_labels":"HUMAN"},{"cleaned":"international trends liver cancer incidence overall histologic subtype 1978 2007 primary liver cancer common histologic types hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc second leading cause cancer death worldwide rising incidence liver cancer low risk areas decreasing incidence high risk areas reported trends thoroughly explored country histologic type examined liver cancer incidence overall histology calendar time birth cohort selected countries 1978 2007 successive 5 year period age standardized incidence rates calculated volumes v ix cancer incidence five continents electronic database ci5plus newly released ci5x volume x database wide global variations persist liver cancer incidence rates liver cancer remain highest asian countries specifically eastern south eastern asian countries rates high risk countries decreasing recent years rates india several low risk countries africa europe americas oceania rise liver cancer rates histologic type tend convey similar temporal profile however thailand france italy icc rates increased hcc rates declined expect rates high risk countries continue decrease population seroprevalence hepatitis b virus hbv continues decline low risk countries targeted screening treatment hepatitis c virus hcv treatment diabetes primary prevention obesity key reducing future liver cancer incidence pubmed","probabilities":0.9799733,"Title":"International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007","Abstract":"Primary liver cancer, the most common histologic types of which are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the second leading cause of cancer death worldwide. While rising incidence of liver cancer in low-risk areas and decreasing incidence in some high-risk areas has been reported, trends have not been thoroughly explored by country or by histologic type. We examined liver cancer incidence overall and by histology by calendar time and birth cohort for selected countries between 1978 and 2007. For each successive 5-year period, age-standardized incidence rates were calculated from volumes V-IX of the Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume X) database. Wide global variations persist in liver cancer incidence. Rates of liver cancer remain highest in Asian countries, specifically Eastern and South-Eastern Asian countries. While rates in most of these high-risk countries have been decreasing in recent years, rates in India and several low-risk countries of Africa, Europe, the Americas, and Oceania have been on the rise. Liver cancer rates by histologic type tend to convey a similar temporal profile. However, in Thailand, France, and Italy, ICC rates have increased while HCC rates have declined. We expect rates in high-risk countries to continue to decrease, as the population seroprevalence of hepatitis B virus (HBV) continues to decline. In low-risk countries, targeted screening and treatment of the hepatitis C virus (HCV), treatment of diabetes and primary prevention of obesity, will be key in reducing future liver cancer incidence.","Source":"PubMed","category":"HUMAN","training_data":"International trends in liver cancer incidence, overall and by histologic subtype, 1978-2007 Primary liver cancer, the most common histologic types of which are hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), is the second leading cause of cancer death worldwide. While rising incidence of liver cancer in low-risk areas and decreasing incidence in some high-risk areas has been reported, trends have not been thoroughly explored by country or by histologic type. We examined liver cancer incidence overall and by histology by calendar time and birth cohort for selected countries between 1978 and 2007. For each successive 5-year period, age-standardized incidence rates were calculated from volumes V-IX of the Cancer Incidence in Five Continents electronic database (CI5plus) and the newly released CI5X (volume X) database. Wide global variations persist in liver cancer incidence. Rates of liver cancer remain highest in Asian countries, specifically Eastern and South-Eastern Asian countries. While rates in most of these high-risk countries have been decreasing in recent years, rates in India and several low-risk countries of Africa, Europe, the Americas, and Oceania have been on the rise. Liver cancer rates by histologic type tend to convey a similar temporal profile. However, in Thailand, France, and Italy, ICC rates have increased while HCC rates have declined. We expect rates in high-risk countries to continue to decrease, as the population seroprevalence of hepatitis B virus (HBV) continues to decline. In low-risk countries, targeted screening and treatment of the hepatitis C virus (HCV), treatment of diabetes and primary prevention of obesity, will be key in reducing future liver cancer incidence. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ee 0207 pe 0029 favorable gallbladder cancer mortality incidence ratios countries good ranking world health system background mortality incidence ratio mir marker reflects clinical outcome cancer treatment mir prognostic marker accessible compared long term follow survival surveys theoretically countries good health care systems favorable outcomes cancer however report yet demonstrated association gallbladder cancer mir world health system ranking methods used linear regression analyze correlation mirs world health organization rankings total expenditures health gross domestic product e gdp 57 countries selected according data quality results results showed high crude rates incidence mortality low mir developed regions among continents europe highest crude rates incidence mortality whereas highest age standardized rates asr incidence mortality asia mir lowest north america highest africa 0 40 1 00 respectively furthermore favorable mirs correlated good rankings high e gdp p 0 01 p 0 030 respectively conclusions mir variation gallbladder cancer therefore associated ranking health system expenditure health stn","probabilities":0.9799733,"Title":"Ee-0207 (Pe-0029) Favorable Gallbladder Cancer Mortality-To-Incidence Ratios Of Countries With Good Ranking Of World'S Health System","Abstract":"Background: The mortality-to-incidence ratio (MIR) is a marker that reflects the clinical outcome of cancer treatment. MIR as a prognostic marker is more accessible when compared with long-term follow-up survival surveys. Theoretically, countries with good health care systems would have favorable outcomes for cancer; however, no report has yet demonstrated an association between gallbladder cancer MIR and the World's Health System ranking. \r\n\r\n Methods: We used linear regression to analyze the correlation of MIRs with the World Health Organization (WHO) rankings and total expenditures on health/gross domestic product (e/GDP) in 57 countries selected according to the data quality. \r\n\r\n Results: The results showed high crude rates of incidence/mortality but low MIR in more developed regions. Among continents, Europe had the highest crude rates of incidence/mortality, whereas the highest age-standardized rates (ASR) of incidence/mortality were in Asia. The MIR was lowest in North America and highest in Africa (0.40 and 1.00, respectively). Furthermore, favorable MIRs were correlated with good WHO rankings and high e/GDP (p = 0.01 and p = 0.030, respectively). \r\n\r\n Conclusions: The MIR variation for gallbladder cancer is therefore associated with the ranking of the health system and the expenditure on health.","Source":"STN","category":"HUMAN","training_data":"Ee-0207 (Pe-0029) Favorable Gallbladder Cancer Mortality-To-Incidence Ratios Of Countries With Good Ranking Of World'S Health System Background: The mortality-to-incidence ratio (MIR) is a marker that reflects the clinical outcome of cancer treatment. MIR as a prognostic marker is more accessible when compared with long-term follow-up survival surveys. Theoretically, countries with good health care systems would have favorable outcomes for cancer; however, no report has yet demonstrated an association between gallbladder cancer MIR and the World's Health System ranking. \r\n\r\n Methods: We used linear regression to analyze the correlation of MIRs with the World Health Organization (WHO) rankings and total expenditures on health/gross domestic product (e/GDP) in 57 countries selected according to the data quality. \r\n\r\n Results: The results showed high crude rates of incidence/mortality but low MIR in more developed regions. Among continents, Europe had the highest crude rates of incidence/mortality, whereas the highest age-standardized rates (ASR) of incidence/mortality were in Asia. The MIR was lowest in North America and highest in Africa (0.40 and 1.00, respectively). Furthermore, favorable MIRs were correlated with good WHO rankings and high e/GDP (p = 0.01 and p = 0.030, respectively). \r\n\r\n Conclusions: The MIR variation for gallbladder cancer is therefore associated with the ranking of the health system and the expenditure on health. STN","prediction_labels":"HUMAN"},{"cleaned":"extracellular vesicles carry microrna 195 intrahepatic cholangiocarcinoma improve survival rat model cancer microenvironment plays central role cancer development growth homeostasis paradigm suggests cancer fibroblasts support cancers probably response stimuli received cancer cells aimed investigating whether extracellular vesicles evs shuttle microrna mir species cancer associated fibroblasts cafs cancer cells end extracted evs according published protocols evs studied mir content quantitative reverse transcription polymerase chain reaction evs transfected select mir species utilized vitro well vivo rat model cholangiocarcinoma cca found mir 195 regulated cca cells well adjoining fibroblasts furthermore report evs shuttle mir 195 fibroblasts cancer cells last show fibroblast derived evs loaded mir 195 administered rat model cca concentrate within tumor decrease size cancers improve survival treated rats conclusion evs play salient role trafficking mir species cancer cells cafs human cca understanding mechanisms may allow devising novel therapeutics hepatology 2017 65 501 514 stn","probabilities":1.0,"Title":"Extracellular Vesicles Carry Microrna-195 To Intrahepatic Cholangiocarcinoma And Improve Survival In A Rat Model","Abstract":"The cancer microenvironment plays a central role in cancer development, growth, and homeostasis. This paradigm suggests that cancer fibroblasts support cancers, probably in response to stimuli received from the cancer cells. We aimed at investigating whether extracellular vesicles (EVs) can shuttle microRNA (miR) species between cancer-associated fibroblasts (CAFs) and cancer cells. To this end, we extracted EVs according to published protocols. EVs were studied for their miR content by quantitative reverse-transcription polymerase chain reaction. EVs were transfected with select miR species and utilized in vitro as well as in vivo in a rat model of cholangiocarcinoma (CCA). We found that miR-195 is down-regulated in CCA cells, as well as in adjoining fibroblasts. Furthermore, we report that EVs shuttle miR-195 from fibroblasts to cancer cells. Last, we show that fibroblast-derived EVs, loaded with miR-195, can be administered in a rat model of CCA, concentrate within the tumor, decrease the size of cancers, and improve survival of treated rats. \n\n Conclusion: EVs play a salient role in trafficking miR species between cancer cells and CAFs in human CCA. Understanding of these mechanisms may allow devising of novel therapeutics. (Hepatology 2017;65:501-514).","Source":"STN","category":"ANIMAL","training_data":"Extracellular Vesicles Carry Microrna-195 To Intrahepatic Cholangiocarcinoma And Improve Survival In A Rat Model The cancer microenvironment plays a central role in cancer development, growth, and homeostasis. This paradigm suggests that cancer fibroblasts support cancers, probably in response to stimuli received from the cancer cells. We aimed at investigating whether extracellular vesicles (EVs) can shuttle microRNA (miR) species between cancer-associated fibroblasts (CAFs) and cancer cells. To this end, we extracted EVs according to published protocols. EVs were studied for their miR content by quantitative reverse-transcription polymerase chain reaction. EVs were transfected with select miR species and utilized in vitro as well as in vivo in a rat model of cholangiocarcinoma (CCA). We found that miR-195 is down-regulated in CCA cells, as well as in adjoining fibroblasts. Furthermore, we report that EVs shuttle miR-195 from fibroblasts to cancer cells. Last, we show that fibroblast-derived EVs, loaded with miR-195, can be administered in a rat model of CCA, concentrate within the tumor, decrease the size of cancers, and improve survival of treated rats. \n\n Conclusion: EVs play a salient role in trafficking miR species between cancer cells and CAFs in human CCA. Understanding of these mechanisms may allow devising of novel therapeutics. (Hepatology 2017;65:501-514). STN","prediction_labels":"ANIMAL"},{"cleaned":"hepatitis b c virus infection risk factor development cholangiocarcinoma objective chronic hepatitis b virus hbv hepatitis c virus hcv infection may involved development cholangiocarcinoma prevalence hbv hcv infection examined patients intrahepatic cholangiocarcinoma icc extrahepatic cholangiocarcinoma ecc methods levels hbv surface antigens hbsag antibodies hbv core antigens hbcab hepatitis c virus antibodies hcv ab determined sera obtained 145 consecutive patients 50 patients icc 95 patients ecc results seroprevalence hbsag 10 icc patients 4 2 ecc patients prevalence hcv ab 20 icc patients 7 4 ecc patients conclusion prevalence hbsag hcv ab 0 8 2 2 1 2 respectively japanese population living tottori area furthermore hbv hcv infection possible risk factor development cholangiocarcinoma therefore surveillance icc ecc needed hbv hcv carriers pubmed","probabilities":0.9799733,"Title":"Hepatitis B and C virus infection is a risk factor for the development of cholangiocarcinoma","Abstract":"OBJECTIVE: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection may be involved in the development of cholangiocarcinoma. The prevalence of HBV and HCV infection was examined in patients with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). METHODS: The levels of HBV surface antigens (HBsAg), antibodies against HBV core antigens (HBcAb) and hepatitis C virus antibodies (HCV-Ab) were determined in sera obtained from 145 consecutive patients (50 patients with ICC, 95 patients with ECC). RESULTS: The seroprevalence of HBsAg was 10% in the ICC patients and 4.2% in the ECC patients. The prevalence of HCV-Ab was 20% in the ICC patients and 7.4% in the ECC patients. CONCLUSION: The prevalence of HBsAg and HCV-Ab is 0.8-2.2% and 1-2%, respectively, in the Japanese population living in the Tottori area. Furthermore, HBV and HCV infection is a possible risk factor for the development of cholangiocarcinoma. Therefore, the surveillance of ICC and ECC is needed in HBV and HCV carriers.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis B and C virus infection is a risk factor for the development of cholangiocarcinoma OBJECTIVE: Chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection may be involved in the development of cholangiocarcinoma. The prevalence of HBV and HCV infection was examined in patients with intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC). METHODS: The levels of HBV surface antigens (HBsAg), antibodies against HBV core antigens (HBcAb) and hepatitis C virus antibodies (HCV-Ab) were determined in sera obtained from 145 consecutive patients (50 patients with ICC, 95 patients with ECC). RESULTS: The seroprevalence of HBsAg was 10% in the ICC patients and 4.2% in the ECC patients. The prevalence of HCV-Ab was 20% in the ICC patients and 7.4% in the ECC patients. CONCLUSION: The prevalence of HBsAg and HCV-Ab is 0.8-2.2% and 1-2%, respectively, in the Japanese population living in the Tottori area. Furthermore, HBV and HCV infection is a possible risk factor for the development of cholangiocarcinoma. Therefore, the surveillance of ICC and ECC is needed in HBV and HCV carriers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"evaluation two inflammation based prognostic scores patients resectable gallbladder carcinoma background survival surgery gallbladder cancer generally poor number inflammation based prognostic scores established help predict survival surgery several types cancer objective study analyze compare utility two inflammation based prognostic scores glasgow prognostic score gps neutrophil lymphocyte ratio nlr predicting survival patients gallbladder cancer surgery curative intent methods retrospectively reviewed medical records 85 patients histologically confirmed resectable gallbladder carcinoma gbc receive curative surgery department univariate multivariate analyses performed evaluate relationship variables overall survival os results significant difference detected os patients low high gps nlr scores univariate analyses using clinicopathological characteristics revealed tumor differentiation tumor invasion lymph node metastasis tumor node metastasis classification system stage positive margin status combined common bile duct resection serum levels c reactive protein albumin carbohydrate antigen 19 9 ca19 9 carcinoembryonic antigen ca125 white blood cell count gps nlr associated os among characteristics multivariate analysis demonstrated high gps independently associated poorer os together tumor invasion lymph node metastasis positive margin status conclusions gps superior nlr respect prognostic value patients gbc surgery curative intent gps associated tumor progression also independent marker poor prognosis pubmed","probabilities":0.962963,"Title":"Evaluation of two inflammation-based prognostic scores in patients with resectable gallbladder carcinoma","Abstract":"BACKGROUND: Survival after surgery for gallbladder cancer is generally poor. A number of inflammation-based prognostic scores have been established to help predict survival after surgery for several types of cancer. The objective of this study was to analyze and compare the utility of two inflammation-based prognostic scores, the Glasgow prognostic score (GPS) and the neutrophil-to-lymphocyte ratio (NLR), for predicting survival in patients with gallbladder cancer after surgery with curative intent. METHODS: We retrospectively reviewed the medical records of 85 patients with histologically confirmed, resectable gallbladder carcinoma (GBC), who were to receive curative surgery in our department. Univariate and multivariate analyses were performed to evaluate the relationship between the variables to overall survival (OS). RESULTS: A significant difference was detected in OS in patients with low and high GPS and NLR scores. Univariate analyses using clinicopathological characteristics revealed that tumor differentiation; tumor invasion; lymph node metastasis; tumor, node, metastasis classification system stage; positive margin status; combined common bile duct resection; serum levels of C-reactive protein, albumin, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen, and CA125; white blood cell count; and GPS and NLR were all associated with OS. Among these characteristics, multivariate analysis demonstrated that a high GPS was independently associated with poorer OS, together with tumor invasion, lymph node metastasis, and positive margin status. CONCLUSIONS: GPS is superior to NLR with respect to its prognostic value for patients with GBC after surgery with curative intent. GPS is not only associated with tumor progression but is also an independent marker of poor prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of two inflammation-based prognostic scores in patients with resectable gallbladder carcinoma BACKGROUND: Survival after surgery for gallbladder cancer is generally poor. A number of inflammation-based prognostic scores have been established to help predict survival after surgery for several types of cancer. The objective of this study was to analyze and compare the utility of two inflammation-based prognostic scores, the Glasgow prognostic score (GPS) and the neutrophil-to-lymphocyte ratio (NLR), for predicting survival in patients with gallbladder cancer after surgery with curative intent. METHODS: We retrospectively reviewed the medical records of 85 patients with histologically confirmed, resectable gallbladder carcinoma (GBC), who were to receive curative surgery in our department. Univariate and multivariate analyses were performed to evaluate the relationship between the variables to overall survival (OS). RESULTS: A significant difference was detected in OS in patients with low and high GPS and NLR scores. Univariate analyses using clinicopathological characteristics revealed that tumor differentiation; tumor invasion; lymph node metastasis; tumor, node, metastasis classification system stage; positive margin status; combined common bile duct resection; serum levels of C-reactive protein, albumin, carbohydrate antigen 19-9 (CA19-9), carcinoembryonic antigen, and CA125; white blood cell count; and GPS and NLR were all associated with OS. Among these characteristics, multivariate analysis demonstrated that a high GPS was independently associated with poorer OS, together with tumor invasion, lymph node metastasis, and positive margin status. CONCLUSIONS: GPS is superior to NLR with respect to its prognostic value for patients with GBC after surgery with curative intent. GPS is not only associated with tumor progression but is also an independent marker of poor prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"plasmalemmal vesicle associated protein plvap new therapeutic target treatment cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Plasmalemmal Vesicle-Associated Protein (Plvap) Is A New Therapeutic Target For Treatment Of Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Plasmalemmal Vesicle-Associated Protein (Plvap) Is A New Therapeutic Target For Treatment Of Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"outcomes borderline resectable intra hepatic cholangiocarcinoma treated resin yttrium 90 radioembolization using mird model dosimetry purpose evaluate efficacy safety transarterial yttrium 90 y90 resin microsphere radioembolization using medical internal radiation dosimetry mird model patients intrahepatic cholangiocarcinoma icc materials irb approved retrospective review 22 consecutive patients 11 men 11 women age 70 8 years icc single center underwent resin y90 april 2015 april 2018 patients treated body surface area model n 7 excluded analysis survival data analyzed kaplan meier method results 15 patients met inclusion exclusion criteria age 69 8 years 60 male patients presented mass forming icc 7 9 3 6 cm good performance status ecog 0 1 normal lfts 15 15 biopsy time diagnosis revealed 33 poorly differentiated icc planning arteriography lung shunt fraction 8 13 extra hepatic vessel embolization 33 treatment dosimetry performed using mird model target dose 120 200 gy y90 treatment performed segmental 53 lobar 47 level prescribed activity 8 1 120 7 mci successfully delivered cases 90 108 prescribed dose y90 treatment provided first line treatment 73 patients grade 3 ctcae v5 0 adverse events occurred 3 15 20 patients y90 treatment provided neo adjuvant intent combination chemotherapy systemic gemcitabine cisplatin 53 patients surgical resection achieved 40 6 15 patients median follow time 18 months iqr 14 27 months median progression free survival 6 months iqr 3 14 months overall survival currently 80 12 15 mortalities occurred patients extra hepatic disease time presentation n 3 one year survival 84 11 13 2 year survival 63 5 8 conclusions transarterial y90 radioembolization resin microspheres using mird dosimetry intrahepatic cholangiocarcinoma safe promising survival outcomes google scholar","probabilities":0.9799733,"Title":"Outcomes For Borderline Resectable Intra-Hepatic Cholangiocarcinoma Treated With Resin Yttrium-90 Radioembolization Using Mird Model Dosimetry","Abstract":"Purpose: To evaluate the efficacy and safety of transarterial\nYttrium-90 (Y90) resin microsphere radioembolization using the Medical Internal Radiation Dosimetry (MIRD) model in patients\nwith intrahepatic cholangiocarcinoma (ICC).\nMaterials: IRB-approved, retrospective review of 22 consecutive\npatients (11 men and 11 women; age, 70±8 years) with ICC at a\nsingle center who underwent resin Y90 between April 2015 to\nApril 2018. Patients treated with the body-surface area model\n(n¼7) were excluded from analysis. Survival data were analyzed\nby the Kaplan-Meier method.\nResults: There were 15 patients who met inclusion and exclusion\ncriteria (Age: 69±8 years; 60% male). Patients presented\nwith mass forming ICC (7.9±3.6 cm), with good performance\nstatus (ECOG 0-1), and normal LFTs (15/15). Biopsy at the time\nof diagnosis revealed 33% with poorly differentiated ICC. After\nplanning arteriography (Lung shunt fraction: 8-13%; extra-hepatic\nvessel embolization: 33%), treatment dosimetry was performed\nusing the MIRD model (target dose: 120-200 Gy). Y90 treatment\nwas performed at a segmental (53%) or lobar (47%) level. The\nprescribed activity (8.1-120.7 mCi) was successfully delivered in\nall cases (90-108% of prescribed dose). Y90 treatment was provided\nas first-line treatment in 73% patients. Grade 3 CTCAE\nv5.0 adverse events occurred in 3/15 (20%) patients. Y90 treatment\nwas provided with neo-adjuvant intent in combination with\nchemotherapy (systemic gemcitabine and cisplatin) in 53% patients.\nSurgical resection was achieved in 40% (6/15) of patients.\nMedian follow-up at this time is 18 months (IQR: 14-27 months).\nMedian progression-free survival was 6 months (IQR: 3-14\nmonths). Overall survival is currently 80% (12/15). All mortalities\noccurred in patients with extra-hepatic disease at the time of\npresentation (n¼3). One-year survival is 84% (11/13) and 2-year\nsurvival is 63% (5/8).\nConclusions: Transarterial Y90 radioembolization with resin\nmicrospheres using MIRD dosimetry for intrahepatic cholangiocarcinoma\nis safe and has promising survival outcomes.","Source":"Google Scholar","category":"HUMAN","training_data":"Outcomes For Borderline Resectable Intra-Hepatic Cholangiocarcinoma Treated With Resin Yttrium-90 Radioembolization Using Mird Model Dosimetry Purpose: To evaluate the efficacy and safety of transarterial\nYttrium-90 (Y90) resin microsphere radioembolization using the Medical Internal Radiation Dosimetry (MIRD) model in patients\nwith intrahepatic cholangiocarcinoma (ICC).\nMaterials: IRB-approved, retrospective review of 22 consecutive\npatients (11 men and 11 women; age, 70±8 years) with ICC at a\nsingle center who underwent resin Y90 between April 2015 to\nApril 2018. Patients treated with the body-surface area model\n(n¼7) were excluded from analysis. Survival data were analyzed\nby the Kaplan-Meier method.\nResults: There were 15 patients who met inclusion and exclusion\ncriteria (Age: 69±8 years; 60% male). Patients presented\nwith mass forming ICC (7.9±3.6 cm), with good performance\nstatus (ECOG 0-1), and normal LFTs (15/15). Biopsy at the time\nof diagnosis revealed 33% with poorly differentiated ICC. After\nplanning arteriography (Lung shunt fraction: 8-13%; extra-hepatic\nvessel embolization: 33%), treatment dosimetry was performed\nusing the MIRD model (target dose: 120-200 Gy). Y90 treatment\nwas performed at a segmental (53%) or lobar (47%) level. The\nprescribed activity (8.1-120.7 mCi) was successfully delivered in\nall cases (90-108% of prescribed dose). Y90 treatment was provided\nas first-line treatment in 73% patients. Grade 3 CTCAE\nv5.0 adverse events occurred in 3/15 (20%) patients. Y90 treatment\nwas provided with neo-adjuvant intent in combination with\nchemotherapy (systemic gemcitabine and cisplatin) in 53% patients.\nSurgical resection was achieved in 40% (6/15) of patients.\nMedian follow-up at this time is 18 months (IQR: 14-27 months).\nMedian progression-free survival was 6 months (IQR: 3-14\nmonths). Overall survival is currently 80% (12/15). All mortalities\noccurred in patients with extra-hepatic disease at the time of\npresentation (n¼3). One-year survival is 84% (11/13) and 2-year\nsurvival is 63% (5/8).\nConclusions: Transarterial Y90 radioembolization with resin\nmicrospheres using MIRD dosimetry for intrahepatic cholangiocarcinoma\nis safe and has promising survival outcomes. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"high glucose enhances progression cholangiocarcinoma cells via stat3 activation epidemiological studies indicated diabetes mellitus dm risk cholangiocarcinoma cca however effects mechanisms high glucose progression cca remain unclear study reports first time enhancing effects high glucose aggressive phenotypes cca cells via stat3 activation cca cells cultured high glucose media exerted significantly higher rates cell proliferation adhesion migration invasion cultured normal glucose phosphokinase array revealed stat3 dominant signal activated response high glucose increased nuclear stat3 p stat3 downstream target proteins cyclin d1 vimentin mmp2 shown underling mechanisms high glucose stimulation link high glucose stat3 activation confirmed tumor tissues cca patients dm exhibited higher stat3 activation without dm moreover levels stat3 activation correlated levels blood glucose finally decreasing level glucose using stat3 inhibitor reduce effects high glucose findings suggest controlling blood glucose using stat3 inhibitor alternative approach may improve therapeutic outcome cca patients dm stn","probabilities":0.9467213,"Title":"High Glucose Enhances Progression Of Cholangiocarcinoma Cells Via Stat3 Activation","Abstract":"Epidemiological studies have indicated diabetes mellitus (DM) as a risk of cholangiocarcinoma (CCA), however, the effects and mechanisms of high glucose on progression of CCA remain unclear. This study reports for the first time of the enhancing effects of high glucose on aggressive phenotypes of CCA cells via STAT3 activation. CCA cells cultured in high glucose media exerted significantly higher rates of cell proliferation, adhesion, migration and invasion than those cultured in normal glucose. The phosphokinase array revealed STAT3 as the dominant signal activated in response to high glucose. Increased nuclear STAT3, p-STAT3 and its downstream target proteins, cyclin D1, vimentin and MMP2, were shown to be underling mechanisms of high glucose stimulation. The link of high glucose and STAT3 activation was confirmed in tumor tissues from CCA patients with DM that exhibited higher STAT3 activation than those without DM. Moreover, the levels of STAT3 activation were correlated with the levels of blood glucose. Finally, decreasing the level of glucose or using a STAT3 inhibitor could reduce the effects of high glucose. These findings suggest that controlling blood glucose or using a STAT3 inhibitor as an alternative approach may improve the therapeutic outcome of CCA patients with DM.","Source":"STN","category":"ANIMAL","training_data":"High Glucose Enhances Progression Of Cholangiocarcinoma Cells Via Stat3 Activation Epidemiological studies have indicated diabetes mellitus (DM) as a risk of cholangiocarcinoma (CCA), however, the effects and mechanisms of high glucose on progression of CCA remain unclear. This study reports for the first time of the enhancing effects of high glucose on aggressive phenotypes of CCA cells via STAT3 activation. CCA cells cultured in high glucose media exerted significantly higher rates of cell proliferation, adhesion, migration and invasion than those cultured in normal glucose. The phosphokinase array revealed STAT3 as the dominant signal activated in response to high glucose. Increased nuclear STAT3, p-STAT3 and its downstream target proteins, cyclin D1, vimentin and MMP2, were shown to be underling mechanisms of high glucose stimulation. The link of high glucose and STAT3 activation was confirmed in tumor tissues from CCA patients with DM that exhibited higher STAT3 activation than those without DM. Moreover, the levels of STAT3 activation were correlated with the levels of blood glucose. Finally, decreasing the level of glucose or using a STAT3 inhibitor could reduce the effects of high glucose. These findings suggest that controlling blood glucose or using a STAT3 inhibitor as an alternative approach may improve the therapeutic outcome of CCA patients with DM. STN","prediction_labels":"ANIMAL"},{"cleaned":"gallstones cholecystectomy relation risk intra extrahepatic cholangiocarcinoma background cholangiocarcinomas highly lethal tumours intrahepatic extrahepatic biliary tract aetiology largely unknown potential roles gallstones gall bladder removal cholecystectomy need addressed large study long follow methods population based nationwide swedish cohort study carried patients hospitalised gallstone diagnosis without gallbladder removal cholecystectomy 1965 2008 identified swedish patient registry cohort followed cancer swedish cancer registry observed numbers intra extrahepatic cholangiocarcinomas developed one year follow compared expected numbers calculated corresponding background population relative risks estimated standardised incidence ratios sirs 95 confidence intervals cis results among 192 960 non cholecystectomised individuals gallstones two fold overall increased risk intra extra hepatic cholangiocarcinomas remained stable follow period sir 2 77 95 ci 2 17 3 49 sir 2 58 95 ci 2 21 3 00 respectively cholecystectomy cohort including 345 251 people 4 854 969 person years 325 incident cholangiocarcinomas identified 98 30 intrahepatic 227 70 extrahepatic initially 1 4 years surgery risk increased intrahepatic cholangiocarcinoma sir 1 80 95 ci 1 19 2 62 extrahepatic cholangiocarcinoma sir 2 29 95 ci 1 83 2 82 increase remained 10 years follow sir 1 10 95 ci 0 79 1 48 sir 0 87 95 ci 0 70 1 07 respectively interpretation gallstones seem increase risk intra extrahepatic cholangiocarcinoma however risk seems decline level background population time cholecystectomy pubmed","probabilities":0.9799733,"Title":"Gallstones and cholecystectomy in relation to risk of intra- and extrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Cholangiocarcinomas are highly lethal tumours of the intrahepatic or extrahepatic biliary tract. The aetiology is largely unknown, and the potential roles of gallstones and gall bladder removal (cholecystectomy) need to be addressed in a large study with a long follow-up. METHODS: A population-based nationwide Swedish cohort study was carried out, in which patients hospitalised for gallstone diagnosis with or without gallbladder removal (cholecystectomy) between 1965 and 2008 were identified in the Swedish Patient Registry. The cohort was followed up for cancer in the Swedish Cancer Registry. The observed numbers of intra- and extrahepatic cholangiocarcinomas that developed after one year of follow-up were compared with the expected numbers, calculated from the corresponding background population, and the relative risks were estimated by standardised incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: Among the 192,960 non-cholecystectomised individuals with gallstones, there was a more than two-fold overall increased risk of both intra- and extra- hepatic cholangiocarcinomas, which remained stable over the follow-up period (SIR 2.77, 95% CI 2.17-3.49, and SIR 2.58, 95% CI 2.21-3.00, respectively). In the cholecystectomy cohort, including 345,251 people and 4,854,969 person-years, 325 incident cholangiocarcinomas were identified, of which 98 (30%) were intrahepatic and 227 (70%) were extrahepatic. Initially (1-4 years after surgery), the risk was increased for both intrahepatic cholangiocarcinoma (SIR 1.80, 95% CI 1.19-2.62) and extrahepatic cholangiocarcinoma (SIR 2.29, 95% CI 1.83-2.82), but no increase remained after 10 years of follow-up or more (SIR 1.10, 95% CI 0.79-1.48, and SIR 0.87, 95% CI 0.70-1.07, respectively). INTERPRETATION: Gallstones seem to increase the risk of both intra- and extrahepatic cholangiocarcinoma. However, this risk seems to decline to the level of the background population with time after cholecystectomy.","Source":"PubMed","category":"HUMAN","training_data":"Gallstones and cholecystectomy in relation to risk of intra- and extrahepatic cholangiocarcinoma BACKGROUND: Cholangiocarcinomas are highly lethal tumours of the intrahepatic or extrahepatic biliary tract. The aetiology is largely unknown, and the potential roles of gallstones and gall bladder removal (cholecystectomy) need to be addressed in a large study with a long follow-up. METHODS: A population-based nationwide Swedish cohort study was carried out, in which patients hospitalised for gallstone diagnosis with or without gallbladder removal (cholecystectomy) between 1965 and 2008 were identified in the Swedish Patient Registry. The cohort was followed up for cancer in the Swedish Cancer Registry. The observed numbers of intra- and extrahepatic cholangiocarcinomas that developed after one year of follow-up were compared with the expected numbers, calculated from the corresponding background population, and the relative risks were estimated by standardised incidence ratios (SIRs) and 95% confidence intervals (CIs). RESULTS: Among the 192,960 non-cholecystectomised individuals with gallstones, there was a more than two-fold overall increased risk of both intra- and extra- hepatic cholangiocarcinomas, which remained stable over the follow-up period (SIR 2.77, 95% CI 2.17-3.49, and SIR 2.58, 95% CI 2.21-3.00, respectively). In the cholecystectomy cohort, including 345,251 people and 4,854,969 person-years, 325 incident cholangiocarcinomas were identified, of which 98 (30%) were intrahepatic and 227 (70%) were extrahepatic. Initially (1-4 years after surgery), the risk was increased for both intrahepatic cholangiocarcinoma (SIR 1.80, 95% CI 1.19-2.62) and extrahepatic cholangiocarcinoma (SIR 2.29, 95% CI 1.83-2.82), but no increase remained after 10 years of follow-up or more (SIR 1.10, 95% CI 0.79-1.48, and SIR 0.87, 95% CI 0.70-1.07, respectively). INTERPRETATION: Gallstones seem to increase the risk of both intra- and extrahepatic cholangiocarcinoma. However, this risk seems to decline to the level of the background population with time after cholecystectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors patients recurrent intrahepatic cholangiocarcinoma curative resection retrospective cohort study background aim study determine outcomes prognostic factors patients recurrent intrahepatic cholangiocarcinoma curative hepatectomy methods clinical histopathological treatment data 53 patients recurrent cholangiocarcinoma curative resection 2005 2015 institutes investigated analyzed univariate multivariate analyses e 788 results recurrent cholangiocarcinoma occurred 53 97 patients underwent curative resection intrahepatic cholangiocarcinoma median overall survival recurrence 13 6 months range 1 55 months multivariate analysis revealed recurrent treatment without surgery p 0 0007 gross appearance except mass forming type p 0 0183 bile duct invasion initial surgery p 0 0093 significant poor prognostic factors recurrent cholangiocarcinoma median survival patients surgical treatment recurrent cholangiocarcinoma 36 7 months versus 13 1 months patients undergo surgery p 0 029 conclusions surgical treatment gross appearance mass forming type absence bile duct invasion independent favorable factors survival among patients recurrent cholangiocarcinoma recommend surgical treatment localized recurrence even occurs early initial hepatectomy pubmed","probabilities":0.9799733,"Title":"Prognostic factors in patients with recurrent intrahepatic cholangiocarcinoma after curative resection: A retrospective cohort study","Abstract":"BACKGROUND: The aim of this study is to determine the outcomes and prognostic factors in patients with recurrent intrahepatic cholangiocarcinoma after curative hepatectomy. METHODS: Clinical, histopathological, and treatment data of 53 patients with recurrent cholangiocarcinoma after curative resection from 2005 to 2015 at our institutes were investigated and analyzed by univariate and multivariate analyses (E-788). RESULTS: Recurrent cholangiocarcinoma occurred in 53 of 97 patients who underwent curative resection for intrahepatic cholangiocarcinoma. The median overall survival after recurrence was 13.6 months (range, 1-55 months). Multivariate analysis revealed that recurrent treatment without surgery (p = 0.0007), gross appearance except for mass-forming type (p = 0.0183) and bile duct invasion at the initial surgery (p = 0.0093) were significant poor prognostic factors in recurrent cholangiocarcinoma. Median survival of patients after surgical treatment for recurrent cholangiocarcinoma was 36.7 months versus 13.1 months in patients who did not undergo surgery (p = 0.029). CONCLUSIONS: Surgical treatment, gross appearance in mass-forming type and the absence of bile duct invasion were independent favorable factors for survival among patients with recurrent cholangiocarcinoma. We recommend surgical treatment for localized recurrence, even if it occurs early after the initial hepatectomy.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors in patients with recurrent intrahepatic cholangiocarcinoma after curative resection: A retrospective cohort study BACKGROUND: The aim of this study is to determine the outcomes and prognostic factors in patients with recurrent intrahepatic cholangiocarcinoma after curative hepatectomy. METHODS: Clinical, histopathological, and treatment data of 53 patients with recurrent cholangiocarcinoma after curative resection from 2005 to 2015 at our institutes were investigated and analyzed by univariate and multivariate analyses (E-788). RESULTS: Recurrent cholangiocarcinoma occurred in 53 of 97 patients who underwent curative resection for intrahepatic cholangiocarcinoma. The median overall survival after recurrence was 13.6 months (range, 1-55 months). Multivariate analysis revealed that recurrent treatment without surgery (p = 0.0007), gross appearance except for mass-forming type (p = 0.0183) and bile duct invasion at the initial surgery (p = 0.0093) were significant poor prognostic factors in recurrent cholangiocarcinoma. Median survival of patients after surgical treatment for recurrent cholangiocarcinoma was 36.7 months versus 13.1 months in patients who did not undergo surgery (p = 0.029). CONCLUSIONS: Surgical treatment, gross appearance in mass-forming type and the absence of bile duct invasion were independent favorable factors for survival among patients with recurrent cholangiocarcinoma. We recommend surgical treatment for localized recurrence, even if it occurs early after the initial hepatectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"unsuspected gallbladder cancer clinical retrospective study background morbidity unsuspected gallbladder carcinoma ugc increased study aimed explore factors may influence therapeutic strategies prognosis ucg additionally long term prognosis laparoscopic open surgeries ugc comparatively investigated methods thirty eight cases ugc enrolled study statistical analysis survival performed using kaplan meier test results examined using log rank test results morbidity ugc 0 43 cancer stagings pt1a one pt1b 11 pt2 14 pt3 10 pt3n1 one pt4 one median lifespan entire cohort 20 0 6 5 months one year survival rate 44 five year survival rate 11 one year recurrence free survival rate 44 three year recurrence free survival rate 0 twenty eight patients sustained cancer recurrence three patients sustained port site cancer recurrence cancer staging p 0 01 radical resection p 0 01 independent factors overall recurrence free survival radical resection improved prognosis patients pt2 stage ugc p 0 05 significant impact prognosis patients pt1b p 0 362 pt3 stage p 0 221 ugc survival rates significantly affected first operation matter laparoscopic surgery open surgery p 0 12 conclusion radical resection surgery recommended pt2 stage ugc difference long term prognosis laparoscopic surgery cholecystectomy open surgery ucg pubmed","probabilities":0.9799733,"Title":"Unsuspected gallbladder cancer: a clinical retrospective study","Abstract":"BACKGROUND: The morbidity of unsuspected gallbladder carcinoma (UGC) has increased. This study was aimed to explore the factors which may influence the therapeutic strategies and prognosis of UCG. Additionally, long-term prognosis of laparoscopic and open surgeries of UGC was comparatively investigated. METHODS: Thirty-eight cases of UGC were enrolled in this study. Statistical analysis of survival was performed using the Kaplan-Meier test and the results were examined using the log-rank test. RESULTS: The morbidity of UGC was 0.43 %. The cancer stagings were: pT1a (one), pT1b (11), pT2 (14), pT3 (10), pT3N1 (one), and pT4 (one). The median lifespan of the entire cohort was 20.0 ± 6.5 months, one-year survival rate was 44 %, and five-year survival rate was 11 %. One-year recurrence- free survival rate was 44 % and three-year recurrence- free survival rate was 0 %. Twenty-eight patients sustained cancer recurrence and three patients sustained port-site cancer recurrence. The cancer staging (P < 0.01) and radical resection (P < 0.01) were independent factors for both overall and recurrence-free survival. Radical resection improved the prognosis of the patients with pT2 stage UGC (P < 0.05), but no significant impact on the prognosis of the patients with pT1b (P = 0.362) or pT3 stage (P = 0.221) UGC. Survival rates were not significantly affected by the first operation no matter it was laparoscopic surgery or open surgery (P = 0.12). CONCLUSION: Radical resection surgery is recommended in pT2 stage UGC. There is no difference for the long-term prognosis between laparoscopic surgery (cholecystectomy) and open surgery of UCG.","Source":"PubMed","category":"HUMAN","training_data":"Unsuspected gallbladder cancer: a clinical retrospective study BACKGROUND: The morbidity of unsuspected gallbladder carcinoma (UGC) has increased. This study was aimed to explore the factors which may influence the therapeutic strategies and prognosis of UCG. Additionally, long-term prognosis of laparoscopic and open surgeries of UGC was comparatively investigated. METHODS: Thirty-eight cases of UGC were enrolled in this study. Statistical analysis of survival was performed using the Kaplan-Meier test and the results were examined using the log-rank test. RESULTS: The morbidity of UGC was 0.43 %. The cancer stagings were: pT1a (one), pT1b (11), pT2 (14), pT3 (10), pT3N1 (one), and pT4 (one). The median lifespan of the entire cohort was 20.0 ± 6.5 months, one-year survival rate was 44 %, and five-year survival rate was 11 %. One-year recurrence- free survival rate was 44 % and three-year recurrence- free survival rate was 0 %. Twenty-eight patients sustained cancer recurrence and three patients sustained port-site cancer recurrence. The cancer staging (P < 0.01) and radical resection (P < 0.01) were independent factors for both overall and recurrence-free survival. Radical resection improved the prognosis of the patients with pT2 stage UGC (P < 0.05), but no significant impact on the prognosis of the patients with pT1b (P = 0.362) or pT3 stage (P = 0.221) UGC. Survival rates were not significantly affected by the first operation no matter it was laparoscopic surgery or open surgery (P = 0.12). CONCLUSION: Radical resection surgery is recommended in pT2 stage UGC. There is no difference for the long-term prognosis between laparoscopic surgery (cholecystectomy) and open surgery of UCG. PubMed","prediction_labels":"HUMAN"},{"cleaned":"post operative lymphocyte count may predict outcome radical resection gallbladder carcinoma background gallbladder carcinoma gbc cancer digestive tract poor prognosis surgical resection potentially curative therapy prognostic value postoperative peripheral blood leukocyte subset count patients cancer fully investigated therefore retrospectively investigated relation ship postoperative peripheral blood lymphocyte count disease free well overall survival radical resection gbc patients methods study subjects 34 patients underwent radical resection gbc january 2005 april 2010 retrospectively investigated relation ship clinicopathological variables including postoperative peripheral blood lymphocyte count disease free well overall survival results univariate analysis disease free survival worse patients intraoperative blood transfusion p 0 0285 tumor node metastasis tnm stage ii p 0 0001 lymphocyte count less 1 000 l p 0 0002 overall survival worse patients tnm stage ii p 0 0002 lymphocyte count less 1 000 l p 0 0151 multivariate analysis tnm stage ii p 0 0089 peripheral blood lymphocyte count less 1 000 l p 0 0365 independent predictors poor disease free survival overall survival tnm stage ii p 0 0230 independent predictor moreover lymphocyte counts less 1 000 l correlated significantly tnm stage ii duration operation greater blood loss presence intraoperative blood transfusion conclusion postoperative peripheral blood lymphocyte count correlates outcome patients gbc treated radical resection stn","probabilities":0.9799733,"Title":"Post-Operative Lymphocyte Count May Predict The Outcome Of Radical Resection For Gallbladder Carcinoma","Abstract":"Background: Gallbladder carcinoma (GBC) is a cancer of the digestive tract with poor prognosis, for which surgical resection is the only potentially curative therapy. The prognostic value of postoperative peripheral blood leukocyte subset count in patients with cancer has not been fully investigated. Therefore, we retrospectively investigated the relation-ship between postoperative peripheral blood lymphocyte count and disease-free as well as overall survival after radical resection of GBC. \r\n\r\n Patients and methods: The study subjects were 34 patients who underwent radical resection for GBC between January 2005 and April 2010. We retrospectively investigated the relation-ship between clinicopathological variables, including postoperative peripheral blood lymphocyte count, and disease-free as well as overall survival. \r\n\r\n Results: In univariate analysis, disease-free survival was worse in patients with intraoperative blood transfusion (p=0.0285), tumor node metastasis (TNM) stage ≥II (p<0.0001), and lymphocyte count of less than 1,000/μl (p=0.0002). Overall survival was worse in patients with TNM stage ≥II (p=0.0002) and lymphocyte count of less than 1,000/μl (p=0.0151). In multivariate analysis, TNM stage ≥II (p<0.0089) and peripheral blood lymphocyte count of less than 1,000/μl (p=0.0365) were independent predictors of poor disease-free survival. For overall survival, TNM stage ≥II (p=0.0230) was the only independent predictor. Moreover, lymphocyte counts of less than 1,000/μl correlated significantly with TNM stage ≥II, duration of operation, greater blood loss, and presence of intraoperative blood transfusion. \r\n\r\n Conclusion: Postoperative peripheral blood lymphocyte count correlates with outcome of patients with GBC treated by radical resection.","Source":"STN","category":"HUMAN","training_data":"Post-Operative Lymphocyte Count May Predict The Outcome Of Radical Resection For Gallbladder Carcinoma Background: Gallbladder carcinoma (GBC) is a cancer of the digestive tract with poor prognosis, for which surgical resection is the only potentially curative therapy. The prognostic value of postoperative peripheral blood leukocyte subset count in patients with cancer has not been fully investigated. Therefore, we retrospectively investigated the relation-ship between postoperative peripheral blood lymphocyte count and disease-free as well as overall survival after radical resection of GBC. \r\n\r\n Patients and methods: The study subjects were 34 patients who underwent radical resection for GBC between January 2005 and April 2010. We retrospectively investigated the relation-ship between clinicopathological variables, including postoperative peripheral blood lymphocyte count, and disease-free as well as overall survival. \r\n\r\n Results: In univariate analysis, disease-free survival was worse in patients with intraoperative blood transfusion (p=0.0285), tumor node metastasis (TNM) stage ≥II (p<0.0001), and lymphocyte count of less than 1,000/μl (p=0.0002). Overall survival was worse in patients with TNM stage ≥II (p=0.0002) and lymphocyte count of less than 1,000/μl (p=0.0151). In multivariate analysis, TNM stage ≥II (p<0.0089) and peripheral blood lymphocyte count of less than 1,000/μl (p=0.0365) were independent predictors of poor disease-free survival. For overall survival, TNM stage ≥II (p=0.0230) was the only independent predictor. Moreover, lymphocyte counts of less than 1,000/μl correlated significantly with TNM stage ≥II, duration of operation, greater blood loss, and presence of intraoperative blood transfusion. \r\n\r\n Conclusion: Postoperative peripheral blood lymphocyte count correlates with outcome of patients with GBC treated by radical resection. STN","prediction_labels":"HUMAN"},{"cleaned":"role neoadjuvant chemotherapy chemoradiotherapy advanced gallbladder cancer systematic review background neoadjuvant chemotherapy advanced gallbladder cancer gbc recently proposed alternative adjuvant chemotherapy potential increase resectability rate overall survival aim undertake systematic review critical appraisal available literature use neoadjuvant chemotherapy nact chemoradiotherapy nacrt treatment advanced gbc methods systematic review carried line meta analysis observational studies epidemiology guidelines primary outcomes clinical benefit rate cbr neoadjuvant therapy defined percentage complete response partial response stable disease resectability rate r0 resection secondary outcomes overall disease free survival results 8 studies met inclusion criteria n 474 398 84 0 received nact 76 16 0 received nacrt 133 434 patients 30 6 progressive disease despite nact nacrt cbr 66 6 17 patients responded chemotherapy proceed surgery 50 4 patients considered suitable surgical resection 191 40 3 underwent curative resection r0 rate whole cohort 35 4 overall survival ranged 18 5 50 1 months underwent curative resection versus 5 0 10 8 months non resected group conclusions insufficient data support routine use nact nacrt advanced gbc benefited third whole cohort eventually achieved r0 resection future studies form randomized controlled trials investigate role neoadjuvant therapy advanced gbc pubmed","probabilities":0.9799733,"Title":"The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer - A systematic review","Abstract":"BACKGROUND: Neoadjuvant chemotherapy for advanced gallbladder cancer (GBC) has recently been proposed as an alternative to adjuvant chemotherapy, with potential increase in resectability rate and overall survival. AIM: To undertake a systematic review and critical appraisal of available literature on the use of neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) in the treatment of advanced GBC. METHODS: Systematic review carried out in line with the Meta-analysis Of Observational Studies in Epidemiology guidelines. Primary outcomes were clinical benefit rate (CBR) of neoadjuvant therapy, defined as percentage of complete response, partial response and stable disease, resectability rate and R0 resection. Secondary outcomes were overall and disease-free survival. RESULTS: 8 studies met the inclusion criteria (n = 474), of which 398 (84.0%) received NACT and 76 (16.0%) received NACRT. 133 of 434 patients (30.6%) had progressive disease despite NACT or NACRT. The CBR was 66.6%. 17% of the patients who responded to chemotherapy did not proceed to surgery. 50.4% of the patients were considered suitable for surgical resection, of which 191 (40.3%) underwent curative resection. The R0 rate for the whole cohort was 35.4%. Overall survival ranged from 18.5 to 50.1 months for those who underwent curative resection versus 5.0-10.8 months for non-resected group. CONCLUSIONS: There is insufficient data to support the routine use of NACT or NACRT in advanced GBC, as this has only benefited a third of whole cohort, who eventually achieved a R0 resection. Future studies should be in the form of randomized controlled trials to investigate the role of neoadjuvant therapy in advanced GBC.","Source":"PubMed","category":"HUMAN","training_data":"The role of neoadjuvant chemotherapy or chemoradiotherapy for advanced gallbladder cancer - A systematic review BACKGROUND: Neoadjuvant chemotherapy for advanced gallbladder cancer (GBC) has recently been proposed as an alternative to adjuvant chemotherapy, with potential increase in resectability rate and overall survival. AIM: To undertake a systematic review and critical appraisal of available literature on the use of neoadjuvant chemotherapy (NACT) or chemoradiotherapy (NACRT) in the treatment of advanced GBC. METHODS: Systematic review carried out in line with the Meta-analysis Of Observational Studies in Epidemiology guidelines. Primary outcomes were clinical benefit rate (CBR) of neoadjuvant therapy, defined as percentage of complete response, partial response and stable disease, resectability rate and R0 resection. Secondary outcomes were overall and disease-free survival. RESULTS: 8 studies met the inclusion criteria (n = 474), of which 398 (84.0%) received NACT and 76 (16.0%) received NACRT. 133 of 434 patients (30.6%) had progressive disease despite NACT or NACRT. The CBR was 66.6%. 17% of the patients who responded to chemotherapy did not proceed to surgery. 50.4% of the patients were considered suitable for surgical resection, of which 191 (40.3%) underwent curative resection. The R0 rate for the whole cohort was 35.4%. Overall survival ranged from 18.5 to 50.1 months for those who underwent curative resection versus 5.0-10.8 months for non-resected group. CONCLUSIONS: There is insufficient data to support the routine use of NACT or NACRT in advanced GBC, as this has only benefited a third of whole cohort, who eventually achieved a R0 resection. Future studies should be in the form of randomized controlled trials to investigate the role of neoadjuvant therapy in advanced GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic nutritional index serves predictive marker survival associates systemic inflammatory response metastatic intrahepatic cholangiocarcinoma objective significance prognostic nutritional index pni widely reported confirmed many types cancers however studies available indicating prognostic power patients intrahepatic cholangiocarcinoma icc thus investigated relationship overall survival os evaluate role predicting survival patients icc patients methods october 2011 october 2015 173 consecutive patients pathologically confirmed locally advanced metastatic icc enrolled first correlations pni clinical factors analyzed among patients next univariate multivariate analyses conducted evaluate association pni os among patients icc addition relationships pni three typical systemic inflammatory response sir markers neutrophil lymphocyte ratio nlr platelet lymphocyte ratio plr lymphocyte monocyte ratio lmr also assessed results lower pni linked shorter os patients icc reflected obviously kaplan meier analyses patients icc divided locally advanced group metastatic group analyses revealed pni associated os locally advanced group however subgroup patients metastatic icc lower pni significantly correlated worsened os os patients low pni 5 months whereas os 10 17 months patients high pni multivariate analyses revealed pni independently correlated os finally proved pni negatively proportional nlr plr positively proportional lmr conclusion results demonstrate decreased pni signifies poor os associated sir patients metastatic icc therefore may serve valuable predictive marker patients metastatic icc stn","probabilities":0.9799733,"Title":"Prognostic Nutritional Index Serves As A Predictive Marker Of Survival And Associates With Systemic Inflammatory Response In Metastatic Intrahepatic Cholangiocarcinoma","Abstract":"Objective: The significance of the prognostic nutritional index (PNI) has been widely reported and confirmed in many types of cancers. However, few studies are available indicating its prognostic power in patients with intrahepatic cholangiocarcinoma (ICC). Thus, we investigated its relationship with overall survival (OS) to evaluate its role in predicting survival in patients with ICC. \r\n\r\n Patients and methods: Between October 2011 and October 2015, 173 consecutive patients with pathologically confirmed locally advanced or metastatic ICC were enrolled. First, the correlations between PNI and clinical factors were analyzed among these patients. Next, univariate and multivariate analyses were conducted to evaluate the association between PNI and OS among these patients with ICC. In addition, the relationships between PNI and three typical systemic inflammatory response (SIR) markers - the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), and the lymphocyte/monocyte ratio (LMR) - were also assessed. \r\n\r\n Results: A lower PNI was linked with a shorter OS in patients with ICC, as reflected obviously in the Kaplan-Meier analyses. The patients with ICC were divided into the locally advanced group and the metastatic group. Further analyses revealed that PNI is not associated with OS in the locally advanced group. However, in the subgroup of patients with metastatic ICC, a lower PNI significantly correlated with a worsened OS. The OS for patients with a low PNI is 5 months, whereas the OS is 10.17 months for patients with a high PNI. Multivariate analyses revealed that PNI is independently correlated with OS. We finally proved that PNI is negatively proportional to NLR and PLR and positively proportional to LMR. \r\n\r\n Conclusion: Our results demonstrate that decreased PNI signifies a poor OS and is associated with SIR in patients with metastatic ICC. Therefore, it may serve as a valuable predictive marker in patients with metastatic ICC.","Source":"STN","category":"HUMAN","training_data":"Prognostic Nutritional Index Serves As A Predictive Marker Of Survival And Associates With Systemic Inflammatory Response In Metastatic Intrahepatic Cholangiocarcinoma Objective: The significance of the prognostic nutritional index (PNI) has been widely reported and confirmed in many types of cancers. However, few studies are available indicating its prognostic power in patients with intrahepatic cholangiocarcinoma (ICC). Thus, we investigated its relationship with overall survival (OS) to evaluate its role in predicting survival in patients with ICC. \r\n\r\n Patients and methods: Between October 2011 and October 2015, 173 consecutive patients with pathologically confirmed locally advanced or metastatic ICC were enrolled. First, the correlations between PNI and clinical factors were analyzed among these patients. Next, univariate and multivariate analyses were conducted to evaluate the association between PNI and OS among these patients with ICC. In addition, the relationships between PNI and three typical systemic inflammatory response (SIR) markers - the neutrophil/lymphocyte ratio (NLR), the platelet/lymphocyte ratio (PLR), and the lymphocyte/monocyte ratio (LMR) - were also assessed. \r\n\r\n Results: A lower PNI was linked with a shorter OS in patients with ICC, as reflected obviously in the Kaplan-Meier analyses. The patients with ICC were divided into the locally advanced group and the metastatic group. Further analyses revealed that PNI is not associated with OS in the locally advanced group. However, in the subgroup of patients with metastatic ICC, a lower PNI significantly correlated with a worsened OS. The OS for patients with a low PNI is 5 months, whereas the OS is 10.17 months for patients with a high PNI. Multivariate analyses revealed that PNI is independently correlated with OS. We finally proved that PNI is negatively proportional to NLR and PLR and positively proportional to LMR. \r\n\r\n Conclusion: Our results demonstrate that decreased PNI signifies a poor OS and is associated with SIR in patients with metastatic ICC. Therefore, it may serve as a valuable predictive marker in patients with metastatic ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer vanishing disease objective gallbladder cancer gbc rare gastrointestinal malignancy retrospective population based study conducted evaluate trends incidence treatment outcome gbc latter three decades south netherlands methods patients diagnosed gbc diagnosed dutch eindhoven cancer registry area 1975 2008 included n 659 trend analyses conducted treatment survival results time period standardized incidence females males plummeted 4 5 0 7 2 0 0 4 per 100 000 inhabitants respectively resection rates decreased 74 3 53 4 chemotherapy radiotherapy rates change used sparingly five year survival remained stable 10 time conclusion age standardized incidence gbc declined drastically last three decades increasing number early cholecystectomies gallstones may play role parallel decreasing incidence stomach cancer effective treatment helicobacter pylori may also resulted lowered incidence gbc pubmed","probabilities":0.9799733,"Title":"Gallbladder cancer, a vanishing disease?","Abstract":"OBJECTIVE: Gallbladder cancer (GBC) is a rare gastrointestinal malignancy. A retrospective population-based study was conducted to evaluate trends in incidence, treatment, and outcome of GBC in the latter three decades in the south of the Netherlands. METHODS: All patients diagnosed with GBC diagnosed in the Dutch Eindhoven Cancer Registry area between 1975 and 2008 were included (n = 659). Trend analyses were conducted for treatment and survival. RESULTS: During this time period, standardized incidence in females and males plummeted from 4.5 to 0.7 and from 2.0 to 0.4 per 100,000 inhabitants, respectively. Resection rates decreased from 74.3 to 53.4 %. Chemotherapy and radiotherapy rates did not change and were used sparingly. Five-year survival remained stable (10 %) over time. CONCLUSION: The age-standardized incidence of GBC declined drastically over the last three decades. An increasing number of early cholecystectomies for gallstones may play a role. Parallel to the decreasing incidence of stomach cancer, the effective treatment of Helicobacter pylori may also have resulted in a lowered incidence of GBC.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder cancer, a vanishing disease? OBJECTIVE: Gallbladder cancer (GBC) is a rare gastrointestinal malignancy. A retrospective population-based study was conducted to evaluate trends in incidence, treatment, and outcome of GBC in the latter three decades in the south of the Netherlands. METHODS: All patients diagnosed with GBC diagnosed in the Dutch Eindhoven Cancer Registry area between 1975 and 2008 were included (n = 659). Trend analyses were conducted for treatment and survival. RESULTS: During this time period, standardized incidence in females and males plummeted from 4.5 to 0.7 and from 2.0 to 0.4 per 100,000 inhabitants, respectively. Resection rates decreased from 74.3 to 53.4 %. Chemotherapy and radiotherapy rates did not change and were used sparingly. Five-year survival remained stable (10 %) over time. CONCLUSION: The age-standardized incidence of GBC declined drastically over the last three decades. An increasing number of early cholecystectomies for gallstones may play a role. Parallel to the decreasing incidence of stomach cancer, the effective treatment of Helicobacter pylori may also have resulted in a lowered incidence of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative bilirubin level predicts overall survival tumor recurrence resection perihilar cholangiocarcinoma patients objective currently correlation preoperative bilirubin level overall survival os remains poorly defined respectable perihilar cholangiocarcinoma cc objectives current study evaluate outcomes perihilar cc resection analyze factors influencing curative resection tumor recurrence os methods 115 patients perihilar cc underwent surgical resection retrospectively analyzed based clinic characteristics operative details tumor recurrence long term survival data results 1 3 5 year os rates resection 75 9 36 5 21 7 whereas corresponding tumor recurrence rates 29 6 70 8 85 3 respectively preoperative bilirubin level combined liver resection resection margin vascular invasion perineural invasion lymph node metastasis tnm stage found correlated os tumor recurrence multivariate analysis showed preoperative bilirubin level together resection margin perineural invasion tnm stage independent predictors os tumor recurrence furthermore preoperative bilirubin level related r0 resection lymph node metastasis tnm stage postoperative liver function recovery conclusion preoperative bilirubin level may effectively reflect severity perihilar cc predict os tumor recurrence resection perihilar cc patients stn","probabilities":0.9799733,"Title":"Preoperative Bilirubin Level Predicts Overall Survival And Tumor Recurrence After Resection For Perihilar Cholangiocarcinoma Patients","Abstract":"Objective: Currently, the correlation between preoperative bilirubin level and overall survival (OS) remains poorly defined in respectable perihilar cholangiocarcinoma (CC). The objectives of the current study were to evaluate the outcomes of perihilar CC after resection and then to analyze factors influencing curative resection, tumor recurrence and OS. \r\n\r\n Methods: 115 patients with perihilar CC underwent surgical resection were retrospectively analyzed based on clinic characteristics, operative details, tumor recurrence and long-term survival data. \r\n\r\n Results: The 1-, 3-, and 5-year OS rates after resection were 75.9%, 36.5%, 21.7%, whereas the corresponding tumor recurrence rates were 29.6%, 70.8%, 85.3%, respectively. Preoperative bilirubin level combined with liver resection, resection margin, vascular invasion and perineural invasion, lymph node metastasis and TNM stage were found to be correlated with OS and tumor recurrence. Multivariate analysis showed that preoperative bilirubin level together with resection margin, perineural invasion, and TNM stage were independent predictors of OS and tumor recurrence. Furthermore, preoperative bilirubin level was related with R0 resection, lymph node metastasis, TNM stage and postoperative liver function recovery. \r\n\r\n Conclusion: Preoperative bilirubin level may effectively reflect the severity of perihilar CC and predict the OS and tumor recurrence after resection for perihilar CC patients.","Source":"STN","category":"HUMAN","training_data":"Preoperative Bilirubin Level Predicts Overall Survival And Tumor Recurrence After Resection For Perihilar Cholangiocarcinoma Patients Objective: Currently, the correlation between preoperative bilirubin level and overall survival (OS) remains poorly defined in respectable perihilar cholangiocarcinoma (CC). The objectives of the current study were to evaluate the outcomes of perihilar CC after resection and then to analyze factors influencing curative resection, tumor recurrence and OS. \r\n\r\n Methods: 115 patients with perihilar CC underwent surgical resection were retrospectively analyzed based on clinic characteristics, operative details, tumor recurrence and long-term survival data. \r\n\r\n Results: The 1-, 3-, and 5-year OS rates after resection were 75.9%, 36.5%, 21.7%, whereas the corresponding tumor recurrence rates were 29.6%, 70.8%, 85.3%, respectively. Preoperative bilirubin level combined with liver resection, resection margin, vascular invasion and perineural invasion, lymph node metastasis and TNM stage were found to be correlated with OS and tumor recurrence. Multivariate analysis showed that preoperative bilirubin level together with resection margin, perineural invasion, and TNM stage were independent predictors of OS and tumor recurrence. Furthermore, preoperative bilirubin level was related with R0 resection, lymph node metastasis, TNM stage and postoperative liver function recovery. \r\n\r\n Conclusion: Preoperative bilirubin level may effectively reflect the severity of perihilar CC and predict the OS and tumor recurrence after resection for perihilar CC patients. STN","prediction_labels":"HUMAN"},{"cleaned":"comparison sixth seventh editions uicc classification intrahepatic cholangiocarcinoma background current seventh edition tnm classification intrahepatic cholangiocarcinoma icc includes tumor number vascular invasion lymph node involvement longer tumor size compared sixth edition impact seventh edition stage based prognostic prediction patients icc evaluated methods 03 2001 02 2013 98 patients diagnosis icc surgically treated center median survival times calculated patients separate classification sixth seventh editions results median overall survival increased patients classified lower tumor stages ii using seventh compared sixth edition stage 54 9 vs 47 3 months stage ii 19 9 vs 18 9 months stage iii 17 2 vs 19 9 months stage iv 23 2 vs 15 3 months respectively seventh edition definition category resulted increased median survival regarding t1 50 4 vs 47 3 months well t2 category 19 9 vs 15 6 months revealed reduced median survival patients within t3 21 6 vs 24 8 months well t4 category 19 9 vs 27 0 months conclusions uicc seventh edition tnm classification icc improves separation patients intermediate stage tumors compared sixth edition prognostic value uicc staging system improved seventh edition trial registration data study retrospectively registered study approved ethic committee medical faculty university hospital essen germany license number 15 6353 bo pubmed","probabilities":0.9799733,"Title":"Comparison of the sixth and the seventh editions of the UICC classification for intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: The current seventh edition of the TNM classification for intrahepatic cholangiocarcinoma (ICC) includes tumor number, vascular invasion, lymph node involvement but no longer the tumor size as compared to the sixth edition. The impact of the seventh edition on stage-based prognostic prediction for patients with ICC was evaluated. METHODS: Between 03/2001 and 02/2013, 98 patients with the diagnosis of an ICC were surgically treated at our center. Median survival times were calculated for these patients after separate classification by both sixth and seventh editions. RESULTS: Median overall survival was increased in patients classified to the lower tumor stages I and II using the seventh as compared to the sixth edition: stage I (54.9 vs. 47.3 months), stage II (19.9 vs. 18.9 months), stage III (17.2 vs. 19.9 months), and stage IV (23.2 vs. 15.3 months), respectively. The seventh edition definition of the T category resulted in an increased median survival regarding the T1 (50.4 vs. 47.3 months) as well as the T2 category (19.9 vs. 15.6 months) and revealed a reduced median survival of patients within the T3 (21.6 vs. 24.8 months) as well as the T4 category (19.9 vs. 27.0 months). CONCLUSIONS: The UICC seventh edition TNM classification for ICC improves separation of patients with intermediate stage tumors as compared to the sixth edition. The prognostic value of the UICC staging system has been improved by the seventh edition. Trial registration The data for this study have been retrospectively registered and the study has been approved by the ethic committee of the medical faculty of the University Hospital of Essen, Germany (license number 15-6353-BO).","Source":"PubMed","category":"HUMAN","training_data":"Comparison of the sixth and the seventh editions of the UICC classification for intrahepatic cholangiocarcinoma BACKGROUND: The current seventh edition of the TNM classification for intrahepatic cholangiocarcinoma (ICC) includes tumor number, vascular invasion, lymph node involvement but no longer the tumor size as compared to the sixth edition. The impact of the seventh edition on stage-based prognostic prediction for patients with ICC was evaluated. METHODS: Between 03/2001 and 02/2013, 98 patients with the diagnosis of an ICC were surgically treated at our center. Median survival times were calculated for these patients after separate classification by both sixth and seventh editions. RESULTS: Median overall survival was increased in patients classified to the lower tumor stages I and II using the seventh as compared to the sixth edition: stage I (54.9 vs. 47.3 months), stage II (19.9 vs. 18.9 months), stage III (17.2 vs. 19.9 months), and stage IV (23.2 vs. 15.3 months), respectively. The seventh edition definition of the T category resulted in an increased median survival regarding the T1 (50.4 vs. 47.3 months) as well as the T2 category (19.9 vs. 15.6 months) and revealed a reduced median survival of patients within the T3 (21.6 vs. 24.8 months) as well as the T4 category (19.9 vs. 27.0 months). CONCLUSIONS: The UICC seventh edition TNM classification for ICC improves separation of patients with intermediate stage tumors as compared to the sixth edition. The prognostic value of the UICC staging system has been improved by the seventh edition. Trial registration The data for this study have been retrospectively registered and the study has been approved by the ethic committee of the medical faculty of the University Hospital of Essen, Germany (license number 15-6353-BO). PubMed","prediction_labels":"HUMAN"},{"cleaned":"immunoreactivity prognostic value tumor associated glycoprotein 72 primary gallbladder carcinoma aim purpose study investigate expression tumor associated glycoprotein 72 tag 72 primary gallbladder carcinoma pgc attempt determine potential usefulness diagnostic prognostic applications methods tissue samples 118 patients pgc 30 patients chronic cholecystitis 20 normal gallbladders stained anti tag 72 antibodies immunohistochemical analysis clinical outcome patients maximum follow 5 years determined 110 118 patients results clinicopathological characteristics carcinomas clinical outcome patients associated tag 72 expression tag 72 expressed frequently cancerous tissues larger size lymph nodes metastasis poor differentiation especially statistical association found advanced uicc stages disease 55 77 65 38 92 86 93 75 100 stages ia ib iia iib iii respectively p 0 02 using proportional hazard model survival rate patients pgc expressing tag 72 significantly lower patients without tag 72 expression p 0 01 including information tag 72 staining patterns within cancerous tissues along clinical cancer staging may improve accuracy predicting patients prognosis conclusion data suggest tag 72 expression associated clinicopathological parameters aggressiveness pgc detection combined cancerous staging may increase ability investigators predict prognosis patients pgc pubmed","probabilities":1.0,"Title":"Immunoreactivity and prognostic value of tumor-associated glycoprotein 72 in primary gallbladder carcinoma","Abstract":"AIM: The purpose of this study was to investigate the expression of tumor-associated glycoprotein 72 (TAG-72) in primary gallbladder carcinoma (PGC) with an attempt to determine the potential usefulness of it in diagnostic and prognostic applications. METHODS: Tissue samples from 118 patients with PGC, 30 patients with chronic cholecystitis, and 20 normal gallbladders were stained with anti-TAG-72 antibodies for immunohistochemical analysis. Then, the clinical outcome of the patients after a maximum follow-up of 5 years was determined in 110 out of 118 patients. RESULTS: Clinicopathological characteristics of the carcinomas and clinical outcome of the patients were associated with the TAG-72 expression. TAG-72 was expressed more frequently in cancerous tissues of larger size, with lymph nodes metastasis, and with poor differentiation. Especially, a statistical association was found with more advanced UICC stages of the disease (55.77%, 65.38%, 92.86%, 93.75% and 100% in stages IA, IB, IIA, IIB, and III, respectively, p=0.02). Using a proportional hazard model, the survival rate of the patients with PGC expressing TAG-72 was significantly lower than the patients without TAG-72 expression (p<0.01), and including information of TAG-72 staining patterns within cancerous tissues along with clinical cancer staging may improve the accuracy of predicting patients' prognosis. CONCLUSION: These data suggest that TAG-72 expression is associated with clinicopathological parameters of aggressiveness in PGC. The detection of it combined with cancerous staging may increase the ability of investigators to predict the prognosis of patients with PGC.","Source":"PubMed","category":"HUMAN","training_data":"Immunoreactivity and prognostic value of tumor-associated glycoprotein 72 in primary gallbladder carcinoma AIM: The purpose of this study was to investigate the expression of tumor-associated glycoprotein 72 (TAG-72) in primary gallbladder carcinoma (PGC) with an attempt to determine the potential usefulness of it in diagnostic and prognostic applications. METHODS: Tissue samples from 118 patients with PGC, 30 patients with chronic cholecystitis, and 20 normal gallbladders were stained with anti-TAG-72 antibodies for immunohistochemical analysis. Then, the clinical outcome of the patients after a maximum follow-up of 5 years was determined in 110 out of 118 patients. RESULTS: Clinicopathological characteristics of the carcinomas and clinical outcome of the patients were associated with the TAG-72 expression. TAG-72 was expressed more frequently in cancerous tissues of larger size, with lymph nodes metastasis, and with poor differentiation. Especially, a statistical association was found with more advanced UICC stages of the disease (55.77%, 65.38%, 92.86%, 93.75% and 100% in stages IA, IB, IIA, IIB, and III, respectively, p=0.02). Using a proportional hazard model, the survival rate of the patients with PGC expressing TAG-72 was significantly lower than the patients without TAG-72 expression (p<0.01), and including information of TAG-72 staining patterns within cancerous tissues along with clinical cancer staging may improve the accuracy of predicting patients' prognosis. CONCLUSION: These data suggest that TAG-72 expression is associated with clinicopathological parameters of aggressiveness in PGC. The detection of it combined with cancerous staging may increase the ability of investigators to predict the prognosis of patients with PGC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treating primary liver cancer hepatic arterial infusion floxuridine dexamethasone addition systemic bevacizumab improve results objectives study investigated efficacy safety adding systemic iv bevacizumab bev hepatic arterial infusion hai floxuridine fudr dexamethasone dex unresectable primary liver cancer methods patients unresectable intrahepatic cholangiocarcinoma icc hepatocellular carcinoma hcc treated hai fudr dex plus iv bev results compared recent study hai without bev similar patient population results twenty two patients 18 icc 4 hcc treated hai fudr dex plus bev 7 31 8 partial response 15 68 2 stable disease median survival 31 1 months ci 14 14 33 59 progression free survival pfs 8 45 months ci 5 53 11 05 hepatic pfs 11 3 months ci 7 93 15 69 previous trial hai alone bev response 50 median survival pfs hepatic pfs 29 5 7 3 10 1 months present trial bilirubin elevation 2 mg dl seen 24 patients biliary stents placed 13 6 versus 5 8 0 respectively hai trial without bev due increased biliary toxicity trial prematurely terminated conclusion adding bev hai fudr dex appeared increase biliary toxicity without clear improvement outcome median pfs 8 45 vs 7 3 months median survival 31 1 vs 29 5 months hai bev vs hai alone groups respectively stn","probabilities":0.9799733,"Title":"Treating Primary Liver Cancer With Hepatic Arterial Infusion Of Floxuridine And Dexamethasone: Does The Addition Of Systemic Bevacizumab Improve Results?","Abstract":"Objectives: This study investigated the efficacy and safety of adding systemic (IV) bevacizumab (Bev) to hepatic arterial infusion (HAI) with floxuridine (FUDR)/dexamethasone (Dex) in unresectable primary liver cancer. \r\n\r\n Methods: Patients with unresectable intrahepatic cholangiocarcinoma (ICC) or hepatocellular carcinoma (HCC) were treated with HAI FUDR/Dex plus IV Bev. Results were compared to a recent study of HAI without Bev in a similar patient population. \r\n\r\n Results: Twenty-two patients (18 ICC, 4 HCC) were treated with HAI FUDR/Dex plus Bev; 7 (31.8%) had partial response and 15 (68.2%) had stable disease. Median survival was 31.1 months (CI 14.14-33.59), progression-free survival (PFS) 8.45 months (CI 5.53-11.05), and hepatic PFS 11.3 months (CI 7.93-15.69). In the previous trial with HAI alone (no Bev), the response was 50%; median survival, PFS, and hepatic PFS were 29.5, 7.3, and 10.1 months. In the present trial, bilirubin elevation (>2 mg/dl) was seen in 24% of patients and biliary stents were placed in 13.6%, versus 5.8 and 0%, respectively, in the HAI trial without Bev. Due to increased biliary toxicity, the trial was prematurely terminated. \r\n\r\n Conclusion: Adding Bev to HAI FUDR/Dex appeared to increase biliary toxicity without clear improvement in outcome (median PFS 8.45 vs. 7.3 months, and median survival 31.1 vs. 29.5 months, for HAI + Bev vs. HAI alone groups, respectively).","Source":"STN","category":"HUMAN","training_data":"Treating Primary Liver Cancer With Hepatic Arterial Infusion Of Floxuridine And Dexamethasone: Does The Addition Of Systemic Bevacizumab Improve Results? Objectives: This study investigated the efficacy and safety of adding systemic (IV) bevacizumab (Bev) to hepatic arterial infusion (HAI) with floxuridine (FUDR)/dexamethasone (Dex) in unresectable primary liver cancer. \r\n\r\n Methods: Patients with unresectable intrahepatic cholangiocarcinoma (ICC) or hepatocellular carcinoma (HCC) were treated with HAI FUDR/Dex plus IV Bev. Results were compared to a recent study of HAI without Bev in a similar patient population. \r\n\r\n Results: Twenty-two patients (18 ICC, 4 HCC) were treated with HAI FUDR/Dex plus Bev; 7 (31.8%) had partial response and 15 (68.2%) had stable disease. Median survival was 31.1 months (CI 14.14-33.59), progression-free survival (PFS) 8.45 months (CI 5.53-11.05), and hepatic PFS 11.3 months (CI 7.93-15.69). In the previous trial with HAI alone (no Bev), the response was 50%; median survival, PFS, and hepatic PFS were 29.5, 7.3, and 10.1 months. In the present trial, bilirubin elevation (>2 mg/dl) was seen in 24% of patients and biliary stents were placed in 13.6%, versus 5.8 and 0%, respectively, in the HAI trial without Bev. Due to increased biliary toxicity, the trial was prematurely terminated. \r\n\r\n Conclusion: Adding Bev to HAI FUDR/Dex appeared to increase biliary toxicity without clear improvement in outcome (median PFS 8.45 vs. 7.3 months, and median survival 31.1 vs. 29.5 months, for HAI + Bev vs. HAI alone groups, respectively). STN","prediction_labels":"HUMAN"},{"cleaned":"simvastatin atorvastatin inhibitors proliferation inducers apoptosis human cholangiocarcinoma cells aims study investigated whether statins induce human cholangiocarcinoma cca cell death apoptosis examined mechanism statins act cells main methods four cca cell lines kku 100 kku m055 kku m214 kku m156 cca cell lines examined hmgcr mrna expression rt pcr method two cca cell lines low high hmgcr mrna expression used evaluate sensitivity two statins simvastatin atorvastatin cytotoxic activity antiproliferative activity cell migratory effects statins cca cells evaluated using sulforhodamine b srb acridine orange ethidium bromide ao eb colony formation assay wound healing assay respectively ros formation measured apoptosis related proteins analyzed western blotting key findings statins induced kku 100 kku m214 cell death time dose dependent manner statins induced cell death potently kku 100 cells exhibiting low hmgcr expression kku m214 cells high hmgcr expression simvastatin potently cytotoxic atorvastatin lower ic50 values treatment statins also caused concentration dependent decline colony forming ability cell migration statins induced reactive oxygen species ros formation kku 100 cells kku m214 cells simvastatin enhanced release cytochrome c caspase 3 increased p21 levels especially kku 100 cells significance statins induced cca cell death inhibited cell migration induced apoptosis cell death probably induced via mitochondrial pathway statins potentially developed novel chemotherapeutic agents cca stn","probabilities":0.9467213,"Title":"Simvastatin And Atorvastatin As Inhibitors Of Proliferation And Inducers Of Apoptosis In Human Cholangiocarcinoma Cells","Abstract":"Aims: In this study, we investigated whether statins induce human cholangiocarcinoma (CCA) cell death and apoptosis, and examined the mechanism by which statins act on cells. \r\n\r\n Main methods: Four CCA cell lines, KKU-100, KKU-M055, KKU-M214, and KKU-M156 CCA cell lines were examined for HMGCR mRNA expression by the RT-PCR method. Two CCA cell lines, with low and high HMGCR mRNA expression, were used to evaluate the sensitivity to two statins, simvastatin and atorvastatin. Cytotoxic activity, antiproliferative activity, and cell migratory effects of the statins on CCA cells were evaluated using sulforhodamine B (SRB) and acridine orange/ethidium bromide (AO/EB), the colony formation assay, and wound healing assay, respectively. ROS formation was measured and apoptosis-related proteins were analyzed by Western blotting. \r\n\r\n Key findings: Both statins induced KKU-100 and KKU-M214 cell death in a time- and dose-dependent manner. Statins induced cell death more potently in the KKU-100 cells exhibiting low HMGCR expression than the KKU-M214 cells which had high HMGCR expression. Simvastatin was more potently cytotoxic than atorvastatin with lower IC50 values. Treatment with statins also caused a concentration-dependent decline in colony forming ability and cell migration. Both statins induced reactive oxygen species (ROS) formation in KKU-100 cells, but not in KKU-M214 cells. Simvastatin enhanced the release of cytochrome c, caspase 3, and increased p21 levels, especially for the KKU-100 cells. \r\n\r\n Significance: Statins induced CCA cell death, inhibited cell migration, and induced apoptosis. Cell death was probably induced via the mitochondrial pathway. Statins could potentially be developed as novel chemotherapeutic agents for CCA.","Source":"STN","category":"ANIMAL","training_data":"Simvastatin And Atorvastatin As Inhibitors Of Proliferation And Inducers Of Apoptosis In Human Cholangiocarcinoma Cells Aims: In this study, we investigated whether statins induce human cholangiocarcinoma (CCA) cell death and apoptosis, and examined the mechanism by which statins act on cells. \r\n\r\n Main methods: Four CCA cell lines, KKU-100, KKU-M055, KKU-M214, and KKU-M156 CCA cell lines were examined for HMGCR mRNA expression by the RT-PCR method. Two CCA cell lines, with low and high HMGCR mRNA expression, were used to evaluate the sensitivity to two statins, simvastatin and atorvastatin. Cytotoxic activity, antiproliferative activity, and cell migratory effects of the statins on CCA cells were evaluated using sulforhodamine B (SRB) and acridine orange/ethidium bromide (AO/EB), the colony formation assay, and wound healing assay, respectively. ROS formation was measured and apoptosis-related proteins were analyzed by Western blotting. \r\n\r\n Key findings: Both statins induced KKU-100 and KKU-M214 cell death in a time- and dose-dependent manner. Statins induced cell death more potently in the KKU-100 cells exhibiting low HMGCR expression than the KKU-M214 cells which had high HMGCR expression. Simvastatin was more potently cytotoxic than atorvastatin with lower IC50 values. Treatment with statins also caused a concentration-dependent decline in colony forming ability and cell migration. Both statins induced reactive oxygen species (ROS) formation in KKU-100 cells, but not in KKU-M214 cells. Simvastatin enhanced the release of cytochrome c, caspase 3, and increased p21 levels, especially for the KKU-100 cells. \r\n\r\n Significance: Statins induced CCA cell death, inhibited cell migration, and induced apoptosis. Cell death was probably induced via the mitochondrial pathway. Statins could potentially be developed as novel chemotherapeutic agents for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"therapeutic testing cholangiocarcinoma male female mice getting copy pasted properly go link google scholar","probabilities":0.9799733,"Title":"Therapeutic Testing Of Cholangiocarcinoma In Male And Female Mice","Abstract":"Not getting copy pasted properly. Go through the link","Source":"Google Scholar","category":"ANIMAL","training_data":"Therapeutic Testing Of Cholangiocarcinoma In Male And Female Mice Not getting copy pasted properly. Go through the link Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"epithelial cell adhesion molecule prognosis marker intrahepatic cholangiocarcinoma background recently identified gene signature intrahepatic cholangiocarcinoma icc stroma demonstrated clinical relevance prognosis upregulated genes included epithelial cell adhesion molecule epcam biomarker cancer stem cells csc hypothesized csc biomarkers predict recurrence resected icc methods functional analysis stroma signature previously obtained immunohistochemistry 40 resected icc performed relationships expression csc markers clinicopathologic factors including survival assessed univariate multivariable analyzes results gene expression profile stroma icc highlighted embryonic stem cells signature immunohistochemistry tissue microarray showed protein level increased expression csc biomarkers stroma icc compared nontumor fibrous liver tissue overexpression epcam stroma icc independent risk factor overall hazard ratio 2 6 95 confidence interval 1 3 5 1 p 0 005 disease free survival hazard ratio 2 2 95 confidence interval 1 2 4 2 p 0 012 addition overexpression epcam nontumor fibrous liver tissue closely correlated worst disease free survival p 0 035 conclusions findings provide new arguments potential role csc icc progression supporting idea targeting csc biomarkers might represent promise personalized treatment pubmed","probabilities":0.962963,"Title":"Epithelial cell adhesion molecule is a prognosis marker for intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC biomarkers could predict recurrence of resected ICC. METHODS: Both functional analysis of the stroma signature previously obtained and immunohistochemistry of 40 resected ICC were performed. The relationships between the expression of CSC markers and clinicopathologic factors including survival were assessed by univariate and multivariable analyzes. RESULTS: Gene expression profile of the stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on tissue microarray showed at a protein level the increased expression of CSC biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The overexpression of EpCAM in the stroma of ICC is an independent risk factor for overall (hazard ratio = 2.6; 95% confidence interval, 1.3-5.1; P = 0.005) and disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2-4.2; P = 0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue is closely correlated with a worst disease-free survival (P = 0.035). CONCLUSIONS: Our findings provide new arguments for a potential role of CSC on ICC progression supporting the idea that targeting CSC biomarkers might represent a promise personalized treatment.","Source":"PubMed","category":"HUMAN","training_data":"Epithelial cell adhesion molecule is a prognosis marker for intrahepatic cholangiocarcinoma BACKGROUND: Recently, we identified a gene signature of intrahepatic cholangiocarcinoma (ICC) stroma and demonstrated its clinical relevance for prognosis. The most upregulated genes included epithelial cell adhesion molecule (EpCAM), a biomarker of cancer stem cells (CSC). We hypothesized that CSC biomarkers could predict recurrence of resected ICC. METHODS: Both functional analysis of the stroma signature previously obtained and immunohistochemistry of 40 resected ICC were performed. The relationships between the expression of CSC markers and clinicopathologic factors including survival were assessed by univariate and multivariable analyzes. RESULTS: Gene expression profile of the stroma of ICC highlighted embryonic stem cells signature. Immunohistochemistry on tissue microarray showed at a protein level the increased expression of CSC biomarkers in the stroma of ICC compared with nontumor fibrous liver tissue. The overexpression of EpCAM in the stroma of ICC is an independent risk factor for overall (hazard ratio = 2.6; 95% confidence interval, 1.3-5.1; P = 0.005) and disease-free survival (hazard ratio = 2.2; 95% confidence interval, 1.2-4.2; P = 0.012). In addition, the overexpression of EpCAM in nontumor fibrous liver tissue is closely correlated with a worst disease-free survival (P = 0.035). CONCLUSIONS: Our findings provide new arguments for a potential role of CSC on ICC progression supporting the idea that targeting CSC biomarkers might represent a promise personalized treatment. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact secreted protein acidic rich cysteine sparc expression prognosis surgical resection biliary carcinoma background secreted protein acidic rich cysteine sparc matricellular protein influences chemotherapy effectiveness prognosis aim study investigate whether sparc expression correlates postoperative survival patients treated surgical resection biliary carcinoma methods sparc expression resected biliary carcinoma specimens investigated immunohistochemically 175 patients relationship sparc expression prognosis surgery evaluated using univariate multivariate analyses results high sparc expression peritumoral stroma found 61 35 patients patients stromal sparc expression significantly associated overall survival os p 0 006 multivariate analysis revealed high stromal sparc expression independent risk factor poor os hr 1 81 p 0 006 moreover high stromal sparc expression independently associated poor prognosis subset 118 patients treated gemcitabine based adjuvant chemotherapy hr 2 04 p 0 010 57 patients receive adjuvant chemotherapy p 0 21 conclusions stromal sparc expression correlated prognosis patients resectable biliary carcinoma significance enhanced patients treated adjuvant gemcitabine based chemotherapy pubmed","probabilities":0.9799733,"Title":"Impact of Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression on Prognosis After Surgical Resection for Biliary Carcinoma","Abstract":"BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that influences chemotherapy effectiveness and prognosis. The aim of this study was to investigate whether SPARC expression correlates with the postoperative survival of patients treated with surgical resection for biliary carcinoma. METHODS: SPARC expression in resected biliary carcinoma specimens was investigated immunohistochemically in 175 patients. The relationship between SPARC expression and prognosis after surgery was evaluated using univariate and multivariate analyses. RESULTS: High SPARC expression in peritumoral stroma was found in 61 (35%) patients. In all patients, stromal SPARC expression was significantly associated with overall survival (OS) (P = 0.006). Multivariate analysis revealed that high stromal SPARC expression was an independent risk factor for poor OS (HR 1.81, P = 0.006). Moreover, high stromal SPARC expression was independently associated with poor prognosis in a subset of 118 patients treated with gemcitabine-based adjuvant chemotherapy (HR 2.04, P = 0.010) but not in the 57 patients who did not receive adjuvant chemotherapy (P = 0.21). CONCLUSIONS: Stromal SPARC expression correlated with the prognosis of patients with resectable biliary carcinoma, and its significance was enhanced in patients treated with adjuvant gemcitabine-based chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Impact of Secreted Protein Acidic and Rich in Cysteine (SPARC) Expression on Prognosis After Surgical Resection for Biliary Carcinoma BACKGROUND: Secreted protein acidic and rich in cysteine (SPARC) is a matricellular protein that influences chemotherapy effectiveness and prognosis. The aim of this study was to investigate whether SPARC expression correlates with the postoperative survival of patients treated with surgical resection for biliary carcinoma. METHODS: SPARC expression in resected biliary carcinoma specimens was investigated immunohistochemically in 175 patients. The relationship between SPARC expression and prognosis after surgery was evaluated using univariate and multivariate analyses. RESULTS: High SPARC expression in peritumoral stroma was found in 61 (35%) patients. In all patients, stromal SPARC expression was significantly associated with overall survival (OS) (P = 0.006). Multivariate analysis revealed that high stromal SPARC expression was an independent risk factor for poor OS (HR 1.81, P = 0.006). Moreover, high stromal SPARC expression was independently associated with poor prognosis in a subset of 118 patients treated with gemcitabine-based adjuvant chemotherapy (HR 2.04, P = 0.010) but not in the 57 patients who did not receive adjuvant chemotherapy (P = 0.21). CONCLUSIONS: Stromal SPARC expression correlated with the prognosis of patients with resectable biliary carcinoma, and its significance was enhanced in patients treated with adjuvant gemcitabine-based chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer newer insights improve outcome gallbladder cancer gbc leading cause cancer related mortality certain geographic areas patients gbc advanced disease presentation precluding curative resection resulting dismal prognosis however recent advances understanding epidemiology pathogenesis coupled development newer diagnostic tools therapeutic options resulted enhanced optimism towards management disease leading risk factors gallstones advancing age female gender anomalous pancreaticobiliary ductal junction certain ethnic groups geographic populations advances radiological imaging advent endoscopic ultrasound facilitated early detection accurate staging tumor high index suspicion high risk groups necessary pick incidental early gbc surgical resection curative patients suspected gbc open surgical resection appropriate stage advocated adjuvant combination chemotherapy molecular targeted therapy emerging effective therapeutic options advanced gbc endoscopic palliation biliary gastric outlet obstruction metallic stents improved quality life prevention remains hitherto less explored option reduce gbc related mortality prophylactic cholecystectomy high risk groups cost effective option multi disciplinary systematic global approach initiate collaborative ventures understand epidemiology standardize management strategies conduct multi centric trials newer therapeutic agents initiate preventive measures pave way future conquest disease pubmed","probabilities":0.9799733,"Title":"Gallbladder cancer: can newer insights improve the outcome?","Abstract":"Gallbladder cancer (GBC) is the leading cause of cancer related mortality in certain geographic areas. Most of the patients with GBC have advanced disease at presentation, precluding curative resection resulting in a dismal prognosis. However, recent advances in the understanding of its epidemiology and pathogenesis coupled with development of newer diagnostic tools and therapeutic options, has resulted in enhanced optimism towards the management of the disease. The leading risk factors are gallstones, advancing age, female gender, anomalous pancreaticobiliary ductal junction, certain ethnic groups and geographic populations. Advances in radiological imaging and the advent of endoscopic ultrasound have facilitated early detection and accurate staging of the tumor. A high index of suspicion in high risk groups is necessary to pick up incidental and early GBC, as surgical resection is curative. In patients with suspected GBC, an open surgical resection that is appropriate for that stage is advocated. Adjuvant combination chemotherapy and molecular targeted therapy are emerging as effective therapeutic options in those with advanced GBC. Endoscopic palliation of biliary and gastric outlet obstruction with metallic stents has improved their quality of life. Prevention remains the hitherto less explored option to reduce GBC related mortality. Prophylactic cholecystectomy in high risk groups is a cost-effective option. A multi-disciplinary systematic global approach to initiate collaborative ventures to understand epidemiology, standardize management strategies, conduct multi-centric trials with newer therapeutic agents and initiate preventive measures, would pave way for the future conquest of the disease.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder cancer: can newer insights improve the outcome? Gallbladder cancer (GBC) is the leading cause of cancer related mortality in certain geographic areas. Most of the patients with GBC have advanced disease at presentation, precluding curative resection resulting in a dismal prognosis. However, recent advances in the understanding of its epidemiology and pathogenesis coupled with development of newer diagnostic tools and therapeutic options, has resulted in enhanced optimism towards the management of the disease. The leading risk factors are gallstones, advancing age, female gender, anomalous pancreaticobiliary ductal junction, certain ethnic groups and geographic populations. Advances in radiological imaging and the advent of endoscopic ultrasound have facilitated early detection and accurate staging of the tumor. A high index of suspicion in high risk groups is necessary to pick up incidental and early GBC, as surgical resection is curative. In patients with suspected GBC, an open surgical resection that is appropriate for that stage is advocated. Adjuvant combination chemotherapy and molecular targeted therapy are emerging as effective therapeutic options in those with advanced GBC. Endoscopic palliation of biliary and gastric outlet obstruction with metallic stents has improved their quality of life. Prevention remains the hitherto less explored option to reduce GBC related mortality. Prophylactic cholecystectomy in high risk groups is a cost-effective option. A multi-disciplinary systematic global approach to initiate collaborative ventures to understand epidemiology, standardize management strategies, conduct multi-centric trials with newer therapeutic agents and initiate preventive measures, would pave way for the future conquest of the disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"trop2 correlates microvessel density poor prognosis hilar cholangiocarcinoma background trophoblast cell surface antigen 2 trop2 found associated tumor progression poor prognosis variety epithelial carcinomas aim study investigate trop2 expression prognostic impact hilar cholangiocarcinoma methods immunohistochemistry quantitative real time pcr used determine trop2 expression surgical specimens 70 hilar cholangiocarcinoma patients receiving radical resection relationship trop2 expression microvessel density investigated standard statistical analysis used evaluate trop2 prognosis significance hilar cholangiocarcinoma results high trop2 expression immunohistochemistry found 43 61 4 70 tumor specimens quantitative real time pcr confirmed trop2 level tumor significantly higher non tumoral biliary tissues p 0 001 significant correlations found trop2 expression histological differentiation p 0 016 tumor stage p 0 031 hilar cholangiocarcinoma trop2 expression correlated microvessel density hilar cholangiocarcinoma p 0 026 high trop2 expression patients significantly poorer overall survival rate low trop2 expression 30 vs 68 5 p 0 001 multivariate cox regression analysis indicated trop2 independent prognostic factor hilar cholangiocarcinoma p 0 004 conclusion trop2 expression correlates microvessel density significantly independent prognostic factor human hilar cholangiocarcinoma pubmed","probabilities":0.962963,"Title":"TROP2 correlates with microvessel density and poor prognosis in hilar cholangiocarcinoma","Abstract":"BACKGROUND: Trophoblast cell surface antigen 2 (TROP2) was found to be associated with tumor progression and poor prognosis in a variety of epithelial carcinomas. The aim of the study was to investigate TROP2 expression and its prognostic impact in hilar cholangiocarcinoma. METHODS: Immunohistochemistry and quantitative real-time PCR were used to determine TROP2 expression in surgical specimens from 70 hilar cholangiocarcinoma patients receiving radical resection. The relationship between TROP2 expression and microvessel density was investigated and standard statistical analysis was used to evaluate TROP2 prognosis significance in hilar cholangiocarcinoma. RESULTS: High TROP2 expression by immunohistochemistry was found in 43 (61.4 %) of the 70 tumor specimens. Quantitative real-time PCR confirmed that TROP2 level in tumor was significantly higher than in non-tumoral biliary tissues (P = 0.001). Significant correlations were found between TROP2 expression and histological differentiation (P = 0.016) and tumor T stage (P = 0.031) in hilar cholangiocarcinoma. TROP2 expression correlated with microvessel density in hilar cholangiocarcinoma (P = 0.026). High TROP2 expression patients had a significantly poorer overall survival rate than those with low TROP2 expression (30 vs. 68.5 %, P = 0.001), and multivariate Cox regression analysis indicated TROP2 as an independent prognostic factor for hilar cholangiocarcinoma (P = 0.004). CONCLUSION: TROP2 expression correlates with microvessel density significantly and is an independent prognostic factor in human hilar cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"TROP2 correlates with microvessel density and poor prognosis in hilar cholangiocarcinoma BACKGROUND: Trophoblast cell surface antigen 2 (TROP2) was found to be associated with tumor progression and poor prognosis in a variety of epithelial carcinomas. The aim of the study was to investigate TROP2 expression and its prognostic impact in hilar cholangiocarcinoma. METHODS: Immunohistochemistry and quantitative real-time PCR were used to determine TROP2 expression in surgical specimens from 70 hilar cholangiocarcinoma patients receiving radical resection. The relationship between TROP2 expression and microvessel density was investigated and standard statistical analysis was used to evaluate TROP2 prognosis significance in hilar cholangiocarcinoma. RESULTS: High TROP2 expression by immunohistochemistry was found in 43 (61.4 %) of the 70 tumor specimens. Quantitative real-time PCR confirmed that TROP2 level in tumor was significantly higher than in non-tumoral biliary tissues (P = 0.001). Significant correlations were found between TROP2 expression and histological differentiation (P = 0.016) and tumor T stage (P = 0.031) in hilar cholangiocarcinoma. TROP2 expression correlated with microvessel density in hilar cholangiocarcinoma (P = 0.026). High TROP2 expression patients had a significantly poorer overall survival rate than those with low TROP2 expression (30 vs. 68.5 %, P = 0.001), and multivariate Cox regression analysis indicated TROP2 as an independent prognostic factor for hilar cholangiocarcinoma (P = 0.004). CONCLUSION: TROP2 expression correlates with microvessel density significantly and is an independent prognostic factor in human hilar cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"management perihilar cholangiocarcinoma era multimodal therapy perihilar cholangiocarcinoma cca second common primary malignant tumor liver usa approximately 3000 cases cca diagnosed annually approximately 50 70 tumors arising hilar plate biliary tree risk factors include advanced age male gender primary sclerosing cholangitis choledochal cysts cholelithiasis parasitic infection inflammatory bowel disease cirrhosis chronic pancreatitis patients typically present jaundice abdominal pain pruritus weight loss mainstays treatment include surgery chemotherapy radiation therapy photodynamic therapy specific preoperative interventions patients perihilar cca include endoscopic retrograde cholangiopancreatography percutanteous transhepatic cholangiography portal vein embolization surgical resection offers chance curative therapy perihilar cca r0 resection utmost importance linked improved survival major hepatic resection needed achieve longitudinal radial margins negative tumor fractionated stereotactic body radiotherapy shown promising results cca perihilar cca typically presents advanced disease many patients receive systemic therapy however response current regimens limited orthotopic liver transplantation offers complete resection locally advanced tumors select patient groups pubmed","probabilities":0.9799733,"Title":"Management of perihilar cholangiocarcinoma in the era of multimodal therapy","Abstract":"Perihilar cholangiocarcinoma (CCA) is the second most common primary malignant tumor of the liver. In the USA, there are approximately 3000 cases of CCA diagnosed annually, with approximately 50-70% of these tumors arising at the hilar plate of the biliary tree. Risk factors include advanced age, male gender, primary sclerosing cholangitis, choledochal cysts, cholelithiasis, parasitic infection, inflammatory bowel disease, cirrhosis and chronic pancreatitis. Patients typically present with jaundice, abdominal pain, pruritus and weight loss. The mainstays of treatment include surgery, chemotherapy, radiation therapy and photodynamic therapy. Specific preoperative interventions for patients with perihilar CCA include endoscopic retrograde cholangiopancreatography, percutanteous transhepatic cholangiography and portal vein embolization. Surgical resection offers the only chance for curative therapy in perihilar CCA. R0 resection is of utmost importance and has been linked to improved survival. Major hepatic resection is needed to achieve both longitudinal and radial margins negative for tumor. Fractionated stereotactic body radiotherapy has shown promising results in CCA. Perihilar CCA typically presents with advanced disease, and many patients receive systemic therapy; however, the response to current regimens is limited. Orthotopic liver transplantation offers complete resection of locally advanced tumors in select patient groups.","Source":"PubMed","category":"HUMAN","training_data":"Management of perihilar cholangiocarcinoma in the era of multimodal therapy Perihilar cholangiocarcinoma (CCA) is the second most common primary malignant tumor of the liver. In the USA, there are approximately 3000 cases of CCA diagnosed annually, with approximately 50-70% of these tumors arising at the hilar plate of the biliary tree. Risk factors include advanced age, male gender, primary sclerosing cholangitis, choledochal cysts, cholelithiasis, parasitic infection, inflammatory bowel disease, cirrhosis and chronic pancreatitis. Patients typically present with jaundice, abdominal pain, pruritus and weight loss. The mainstays of treatment include surgery, chemotherapy, radiation therapy and photodynamic therapy. Specific preoperative interventions for patients with perihilar CCA include endoscopic retrograde cholangiopancreatography, percutanteous transhepatic cholangiography and portal vein embolization. Surgical resection offers the only chance for curative therapy in perihilar CCA. R0 resection is of utmost importance and has been linked to improved survival. Major hepatic resection is needed to achieve both longitudinal and radial margins negative for tumor. Fractionated stereotactic body radiotherapy has shown promising results in CCA. Perihilar CCA typically presents with advanced disease, and many patients receive systemic therapy; however, the response to current regimens is limited. Orthotopic liver transplantation offers complete resection of locally advanced tumors in select patient groups. PubMed","prediction_labels":"HUMAN"},{"cleaned":"liver transplantation reconsidered patients intrahepatic cholangiocarcinoma systematic review meta regression analysis epidemiologic evidence abstract available google scholar","probabilities":0.9799733,"Title":"Should Liver Transplantation Be Reconsidered In Patients With Intrahepatic Cholangiocarcinoma? A Systematic Review And Meta-Regression Analysis Of Epidemiologic Evidence","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Should Liver Transplantation Be Reconsidered In Patients With Intrahepatic Cholangiocarcinoma? A Systematic Review And Meta-Regression Analysis Of Epidemiologic Evidence Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"one stage resection bismuth type iv hilar cholangiocarcinoma high hilar resection parenchyma preserving strategies cohort study background bismuth type iv hilar cholangiocarcinoma hc tumors usually considered unresectable strategies high hilar resection preserving liver parenchyma achieve potentially one stage curative resection condition aim present study investigate feasibility safety available strategies methods fifty one consecutive patients bismuth type iv hc underwent one stage resection retrospectively reviewed regard curative resection rate remnant liver volume morbidity mortality survival time results total median survival time 29 months r 0 curative resection rate 57 8 ratio remnant liver volume rlv standard liver volume slv ranged 35 0 60 6 mean 44 5 hospital mortality morbidity rates 3 9 37 2 respectively r0 patients survival significant difference bilioenteric anastomosis hepatoenteric anastomosis p 0 714 conclusions combined caudate lobe high hilar resection cchr technically safe oncologically justifiable adopted high cure rate one stage resection procedure patients bismuth type iv hc whose total bilirubin level less 20 mg l whose direct bilirubin 60 total bilirubin pubmed","probabilities":0.9799733,"Title":"One-stage resection for Bismuth type IV hilar cholangiocarcinoma with high hilar resection and parenchyma-preserving strategies: a cohort study","Abstract":"BACKGROUND: Bismuth type IV hilar cholangiocarcinoma (HC) tumors are usually considered unresectable. The strategies of high hilar resection while preserving liver parenchyma can achieve potentially one-stage curative resection for this condition. The aim of the present study was to investigate the feasibility and safety of available strategies. METHODS: Fifty-one consecutive patients with bismuth type IV HC who underwent one-stage resection were retrospectively reviewed with regard to curative resection rate, remnant liver volume, morbidity, mortality, and survival time. RESULTS: The total median survival time was 29 months. The R(0) (curative resection) rate was 57.8%. The ratio of the remnant liver volume (RLV) to the standard liver volume (SLV) ranged from 35.0 to 60.6%, with a mean of 44.5%. The in-hospital mortality and morbidity rates were 3.9 and 37.2%, respectively. In the R0 patients' survival, there was not a significant difference between bilioenteric anastomosis and hepatoenteric anastomosis (P = 0.714). CONCLUSIONS: Combined caudate lobe and high hilar resection (CCHR) is technically safe and oncologically justifiable and could be adopted with a high cure rate as a one-stage resection procedure for most patients with Bismuth type IV HC whose total bilirubin level is less than 20 mg/L and whose direct bilirubin is more than 60% of total bilirubin.","Source":"PubMed","category":"HUMAN","training_data":"One-stage resection for Bismuth type IV hilar cholangiocarcinoma with high hilar resection and parenchyma-preserving strategies: a cohort study BACKGROUND: Bismuth type IV hilar cholangiocarcinoma (HC) tumors are usually considered unresectable. The strategies of high hilar resection while preserving liver parenchyma can achieve potentially one-stage curative resection for this condition. The aim of the present study was to investigate the feasibility and safety of available strategies. METHODS: Fifty-one consecutive patients with bismuth type IV HC who underwent one-stage resection were retrospectively reviewed with regard to curative resection rate, remnant liver volume, morbidity, mortality, and survival time. RESULTS: The total median survival time was 29 months. The R(0) (curative resection) rate was 57.8%. The ratio of the remnant liver volume (RLV) to the standard liver volume (SLV) ranged from 35.0 to 60.6%, with a mean of 44.5%. The in-hospital mortality and morbidity rates were 3.9 and 37.2%, respectively. In the R0 patients' survival, there was not a significant difference between bilioenteric anastomosis and hepatoenteric anastomosis (P = 0.714). CONCLUSIONS: Combined caudate lobe and high hilar resection (CCHR) is technically safe and oncologically justifiable and could be adopted with a high cure rate as a one-stage resection procedure for most patients with Bismuth type IV HC whose total bilirubin level is less than 20 mg/L and whose direct bilirubin is more than 60% of total bilirubin. PubMed","prediction_labels":"HUMAN"},{"cleaned":"suvmax measured fdg pet ct prognostic value survival bile duct gallbladder cancer background aims studies assessed prognostic value primary tumor maximum standardized uptake value suv max measured 2 18 f fluoro 2 deoxy d glucose pet ct patients bile duct gallbladder cancer methods retrospective analysis 61 patients confirmed bile duct gallbladder cancer underwent fdg pet ct kangbuk samsung medical center seoul korea april 2008 april 2011 prognostic significance suv max clinicopathological variables assessed results twenty three patients diagnosed common bile duct cancer 17 hilar bile duct cancer 12 intrahepatic bile duct cancer nine gallbladder cancer univariate analysis diagnosis intrahepatic cholangiocarcinoma gallbladder cancer mass forming type poorly differentiated cell type nonsurgical treatment advanced american joint committee cancer ajcc staging primary tumor suv max significant predictors poor overall survival multivariate analysis adjusted age sex primary tumor suv max hazard ratio hr 4 526 95 ci 1 813 11 299 advanced ajcc staging hr 4 843 95 ci 1 760 13 328 nonsurgical treatment hr 6 029 95 ci 1 989 18 271 independently associated poor overall survival conclusions primary tumor suv max measured fdg pet ct independent significant prognostic factor overall survival bile duct gallbladder cancer stn","probabilities":0.54545456,"Title":"Suvmax Measured On Fdg Pet-Ct Is A Prognostic Value For Survival In Bile Duct And Gallbladder Cancer","Abstract":"Background/aims: Few studies have assessed the prognostic value of the primary tumor maximum standardized uptake value (SUV max) measured by 2-[(18)F]-fluoro-2-deoxy-D-glucose PET-CT for patients with bile duct and gallbladder cancer. \n\n Methods: A retrospective analysis of 61 patients with confirmed bile duct and gallbladder cancer who underwent FDG PET-CT in Kangbuk Samsung Medical Center (Seoul, Korea) from April 2008 to April 2011. Prognostic significance of SUV max and other clinicopathological variables was assessed. \n\n Results: Twenty-three patients were diagnosed as common bile duct cancer, 17 as hilar bile duct cancer, 12 as intrahepatic bile duct cancer, and nine as gallbladder cancer. In univariate analysis, diagnosis of intrahepatic cholangiocarcinoma and gallbladder cancer, mass forming type, poorly differentiated cell type, nonsurgical treatment, advanced American Joint Committee on Cancer (AJCC) staging and primary tumor SUV max were significant predictors of poor overall survival. In multivariate analysis adjusted for age and sex, primary tumor SUV max (hazard ratio [HR], 4.526; 95% CI, 1.813-11.299), advanced AJCC staging (HR, 4.843; 95% CI, 1.760-13.328), and nonsurgical treatment (HR, 6.029; 95% CI, 1.989-18.271) were independently associated with poor overall survival. \n\n Conclusions: Primary tumor SUV max measured by FDG PET-CT is an independent and significant prognostic factor for overall survival in bile duct and gallbladder cancer.","Source":"STN","category":"HUMAN","training_data":"Suvmax Measured On Fdg Pet-Ct Is A Prognostic Value For Survival In Bile Duct And Gallbladder Cancer Background/aims: Few studies have assessed the prognostic value of the primary tumor maximum standardized uptake value (SUV max) measured by 2-[(18)F]-fluoro-2-deoxy-D-glucose PET-CT for patients with bile duct and gallbladder cancer. \n\n Methods: A retrospective analysis of 61 patients with confirmed bile duct and gallbladder cancer who underwent FDG PET-CT in Kangbuk Samsung Medical Center (Seoul, Korea) from April 2008 to April 2011. Prognostic significance of SUV max and other clinicopathological variables was assessed. \n\n Results: Twenty-three patients were diagnosed as common bile duct cancer, 17 as hilar bile duct cancer, 12 as intrahepatic bile duct cancer, and nine as gallbladder cancer. In univariate analysis, diagnosis of intrahepatic cholangiocarcinoma and gallbladder cancer, mass forming type, poorly differentiated cell type, nonsurgical treatment, advanced American Joint Committee on Cancer (AJCC) staging and primary tumor SUV max were significant predictors of poor overall survival. In multivariate analysis adjusted for age and sex, primary tumor SUV max (hazard ratio [HR], 4.526; 95% CI, 1.813-11.299), advanced AJCC staging (HR, 4.843; 95% CI, 1.760-13.328), and nonsurgical treatment (HR, 6.029; 95% CI, 1.989-18.271) were independently associated with poor overall survival. \n\n Conclusions: Primary tumor SUV max measured by FDG PET-CT is an independent and significant prognostic factor for overall survival in bile duct and gallbladder cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"trends incidence intrahepatic cholangiocarcinoma united states 2004 2014 abstract available google scholar","probabilities":0.9799733,"Title":"Trends In The Incidence Of Intrahepatic Cholangiocarcinoma In The United States 2004 -2014","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Trends In The Incidence Of Intrahepatic Cholangiocarcinoma In The United States 2004 -2014 Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"low power photodynamic therapy induces survival signaling perihilar cholangiocarcinoma cells background photodynamic therapy pdt solid cancers comprises administration photosensitizer followed illumination photosensitizer replete tumor laser light induces state local oxidative stress culminating destruction tumor tissue microvasculature induction anti tumor immune response however tumor types including perihilar cholangiocarcinoma relatively refractory pdt may attributable activation survival pathways tumor cells following pdt e activator protein 1 ap 1 nuclear factor kappa light polypeptide gene enhancer b cells nf b hypoxia inducible factor 1 alpha hif 1 nuclear factor erythroid derived 2 like 2 nfe2l2 unfolded protein response mediated pathways methods assess activation survival pathways pdt human perihilar cholangiocarcinoma sk cha 1 cells subjected pdt zinc phthalocyanine znpc encapsulating liposomes following 30 minute incubation liposomes cells either left untreated treated low 50 mw high 500 mw laser power cumulative light dose 15 j cm 2 cells harvested 90 min post pdt whole genome expression analysis performed using illumina humanht 12 v4 expression beadchips data interpreted context survival pathways addition safety znpc encapsulating liposomes tested vitro vivo results pdt treated sk cha 1 cells exhibited activation hypoxia induced stress response via hif 1 initiation pro inflammatory response via nf b pdt low laser power particular caused extensive survival signaling evidenced significant upregulation hif 1 p 0 001 nf b related p 0 001 genes low power pdt less lethal sk cha 1 cells 90 min post pdt confirmed annexin v propidium iodide staining vitro toxicogenomics toxicological testing chicken embryos mice revealed znpc encapsulating liposomes non toxic conclusions pdt treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling may translate suboptimal therapeutic response possibly tumor recurrence findings encourage development photosensitizer delivery systems co encapsulated inhibitors survival pathways stn","probabilities":1.0,"Title":"Low-Power Photodynamic Therapy Induces Survival Signaling In Perihilar Cholangiocarcinoma Cells","Abstract":"Background: Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways). \r\n\r\n Methods: To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm(2)). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo. \r\n\r\n Results: PDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic. \r\n\r\n Conclusions: PDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways.","Source":"STN","category":"ANIMAL","training_data":"Low-Power Photodynamic Therapy Induces Survival Signaling In Perihilar Cholangiocarcinoma Cells Background: Photodynamic therapy (PDT) of solid cancers comprises the administration of a photosensitizer followed by illumination of the photosensitizer-replete tumor with laser light. This induces a state of local oxidative stress, culminating in the destruction of tumor tissue and microvasculature and induction of an anti-tumor immune response. However, some tumor types, including perihilar cholangiocarcinoma, are relatively refractory to PDT, which may be attributable to the activation of survival pathways in tumor cells following PDT (i.e., activator protein 1 (AP-1)-, nuclear factor of kappa light polypeptide gene enhancer in B-cells (NF-κB)-, hypoxia-inducible factor 1-alpha (HIF-1α)-, nuclear factor (erythroid-derived 2)-like 2 (NFE2L2)-, and unfolded protein response-mediated pathways). \r\n\r\n Methods: To assess the activation of survival pathways after PDT, human perihilar cholangiocarcinoma (SK-ChA-1) cells were subjected to PDT with zinc phthalocyanine (ZnPC)-encapsulating liposomes. Following 30-minute incubation with liposomes, the cells were either left untreated or treated at low (50 mW) or high (500 mW) laser power (cumulative light dose of 15 J/cm(2)). Cells were harvested 90 min post-PDT and whole genome expression analysis was performed using Illumina HumanHT-12 v4 expression beadchips. The data were interpreted in the context of the survival pathways. In addition, the safety of ZnPC-encapsulating liposomes was tested both in vitro and in vivo. \r\n\r\n Results: PDT-treated SK-ChA-1 cells exhibited activation of the hypoxia-induced stress response via HIF-1α and initiation of the pro-inflammatory response via NF-кB. PDT at low laser power in particular caused extensive survival signaling, as evidenced by the significant upregulation of HIF-1- (P < 0.001) and NF-кB-related (P < 0.001) genes. Low-power PDT was less lethal to SK-ChA-1 cells 90 min post-PDT, confirmed by annexin V/propidium iodide staining. In vitro toxicogenomics and toxicological testing in chicken embryos and mice revealed that the ZnPC-encapsulating liposomes are non-toxic. \r\n\r\n Conclusions: PDT-treated perihilar cholangiocarcinoma cells exhibit extensive survival signaling that may translate to a suboptimal therapeutic response and possibly tumor recurrence. These findings encourage the development of photosensitizer delivery systems with co-encapsulated inhibitors of survival pathways. STN","prediction_labels":"ANIMAL"},{"cleaned":"clinicopathological characteristics outcomes rare histologic subtypes gallbladder cancer two decades population based study background limited literature clinicopathological characteristics outcomes rare histologic variants gallbladder cancer gbc methods using seer database surgically managed gbc patients microscopically confirmed adenocarcinoma adenosquamous squamous cell carcinoma papillary carcinoma identified 1988 2009 patients second primary cancer distant metastasis presentation excluded effect clinicopathological variables overall survival os disease specific survival dss analyzed using univariate multivariate proportional hazards modeling associations considered statistically significant alpha error 0 01 results 4738 cases 217 adenosquamous squamous 4 6 367 papillary 7 7 4154 adenocarcinomas 87 7 identified median age 72 years higher tumor grade grade 2 3 4 versus grade 1 higher stage t2 t3 t4 versus t1 lymph node positivity n1 versus n0 adenosquamous squamous histology versus adenocarcinoma worse os dss p 001 papillary gbc better os dss adenocarcinoma hr 0 7 p 001 radical surgery versus simple cholecystectomy better os hr 0 83 p 0 002 multivariate analysis os rates 3 5 years 0 56 0 44 papillary 0 3 0 22 adenocarcinoma 0 14 0 12 adenosquamous squamous histology dss rates 3 5 years 0 67 0 61 papillary 0 38 0 31 adenocarcinoma 0 17 0 16 adenosquamous squamous subtypes respectively conclusion papillary gbc better survival outcomes adenosquamous squamous gbc worse survival outcomes compared gallbladder adenocarcinoma pubmed","probabilities":0.962963,"Title":"Clinicopathological characteristics and outcomes of rare histologic subtypes of gallbladder cancer over two decades: A population-based study","Abstract":"BACKGROUND: There is limited literature about the clinicopathological characteristics and outcomes of rare histologic variants of gallbladder cancer (GBC). METHODS: Using SEER database, surgically managed GBC patients with microscopically confirmed adenocarcinoma, adenosquamous/squamous cell carcinoma and papillary carcinoma were identified from 1988 to 2009. Patients with second primary cancer and distant metastasis at presentation were excluded. The effect of clinicopathological variables on overall survival (OS) and disease specific survival (DSS) were analyzed using univariate and multivariate proportional hazards modeling. All associations were considered statistically significant at an alpha error of 0.01. RESULTS: Out of 4738 cases, 217 adenosquamous/squamous (4.6%), 367 papillary (7.7%), and 4154 adenocarcinomas (87.7%) were identified. Median age was 72 years. Higher tumor grade (grade 2, 3, 4 versus grade 1), higher T stage (T2, T3, T4 versus T1), lymph node positivity (N1 versus N0) and adenosquamous/squamous histology (versus adenocarcinoma) had worse OS and DSS (p < .001). Papillary GBC had better OS and DSS than adenocarcinoma (HR = 0.7; p < .001). Radical surgery (versus simple cholecystectomy) had better OS (HR = 0.83, p = 0.002) in multivariate analysis. OS rates at 3 and 5 years were 0.56 and 0.44 for papillary, 0.3 and 0.22 for adenocarcinoma, and 0.14 and 0.12 for adenosquamous/squamous histology, while DSS rates at 3 and 5 years were 0.67 and 0.61 for papillary, 0.38 and 0.31 for adenocarcinoma, and 0.17 and 0.16 for adenosquamous/squamous subtypes respectively. CONCLUSION: Papillary GBC had better survival outcomes while adenosquamous/squamous GBC had worse survival outcomes compared to gallbladder adenocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological characteristics and outcomes of rare histologic subtypes of gallbladder cancer over two decades: A population-based study BACKGROUND: There is limited literature about the clinicopathological characteristics and outcomes of rare histologic variants of gallbladder cancer (GBC). METHODS: Using SEER database, surgically managed GBC patients with microscopically confirmed adenocarcinoma, adenosquamous/squamous cell carcinoma and papillary carcinoma were identified from 1988 to 2009. Patients with second primary cancer and distant metastasis at presentation were excluded. The effect of clinicopathological variables on overall survival (OS) and disease specific survival (DSS) were analyzed using univariate and multivariate proportional hazards modeling. All associations were considered statistically significant at an alpha error of 0.01. RESULTS: Out of 4738 cases, 217 adenosquamous/squamous (4.6%), 367 papillary (7.7%), and 4154 adenocarcinomas (87.7%) were identified. Median age was 72 years. Higher tumor grade (grade 2, 3, 4 versus grade 1), higher T stage (T2, T3, T4 versus T1), lymph node positivity (N1 versus N0) and adenosquamous/squamous histology (versus adenocarcinoma) had worse OS and DSS (p < .001). Papillary GBC had better OS and DSS than adenocarcinoma (HR = 0.7; p < .001). Radical surgery (versus simple cholecystectomy) had better OS (HR = 0.83, p = 0.002) in multivariate analysis. OS rates at 3 and 5 years were 0.56 and 0.44 for papillary, 0.3 and 0.22 for adenocarcinoma, and 0.14 and 0.12 for adenosquamous/squamous histology, while DSS rates at 3 and 5 years were 0.67 and 0.61 for papillary, 0.38 and 0.31 for adenocarcinoma, and 0.17 and 0.16 for adenosquamous/squamous subtypes respectively. CONCLUSION: Papillary GBC had better survival outcomes while adenosquamous/squamous GBC had worse survival outcomes compared to gallbladder adenocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"inflammatory inception gallbladder cancer gallbladder cancer lethal disease notable geographical variations worldwide predilection towards women main risk factor prolonged exposure gallstones although bacterial infections inflammatory conditions also associated recurrent cycles gallbladder epithelium damage repair enable chronic inflammatory environment promotes progressive morphological impairment metaplasia dysplasia carcinoma along cumulative genome instability inactivation tp53 mutated 50 gbc cases seems earliest one important carcinogenic pathways involved increased cell turnover oxidative stress promote early alteration tp53 cell cycle deregulation apoptosis replicative senescence review discuss evidence role inflammation gallbladder carcinogenesis obtained epidemiological studies genome wide association studies experimental carcinogenesis morphogenetic studies comparative studies inflammation driven malignancies evidence strongly supports chronic unresolved inflammation main carcinogenic mechanism gallbladder cancer regardless initial etiologic trigger given central role inflammation evaluation potential gbc prevention removing causes inflammation using anti inflammatory drugs high risk populations may warranted pubmed","probabilities":0.962963,"Title":"The inflammatory inception of gallbladder cancer","Abstract":"Gallbladder cancer is a lethal disease with notable geographical variations worldwide and a predilection towards women. Its main risk factor is prolonged exposure to gallstones, although bacterial infections and other inflammatory conditions are also associated. The recurrent cycles of gallbladder epithelium damage and repair enable a chronic inflammatory environment that promotes progressive morphological impairment through a metaplasia-dysplasia-carcinoma, along with cumulative genome instability. Inactivation of TP53, which is mutated in over 50% of GBC cases, seems to be the earliest and one of the most important carcinogenic pathways involved. Increased cell turnover and oxidative stress promote early alteration of TP53, cell cycle deregulation, apoptosis and replicative senescence. In this review, we will discuss evidence for the role of inflammation in gallbladder carcinogenesis obtained through epidemiological studies, genome-wide association studies, experimental carcinogenesis, morphogenetic studies and comparative studies with other inflammation-driven malignancies. The evidence strongly supports chronic, unresolved inflammation as the main carcinogenic mechanism of gallbladder cancer, regardless of the initial etiologic trigger. Given this central role of inflammation, evaluation of the potential for GBC prevention removing causes of inflammation or using anti-inflammatory drugs in high-risk populations may be warranted.","Source":"PubMed","category":"HUMAN","training_data":"The inflammatory inception of gallbladder cancer Gallbladder cancer is a lethal disease with notable geographical variations worldwide and a predilection towards women. Its main risk factor is prolonged exposure to gallstones, although bacterial infections and other inflammatory conditions are also associated. The recurrent cycles of gallbladder epithelium damage and repair enable a chronic inflammatory environment that promotes progressive morphological impairment through a metaplasia-dysplasia-carcinoma, along with cumulative genome instability. Inactivation of TP53, which is mutated in over 50% of GBC cases, seems to be the earliest and one of the most important carcinogenic pathways involved. Increased cell turnover and oxidative stress promote early alteration of TP53, cell cycle deregulation, apoptosis and replicative senescence. In this review, we will discuss evidence for the role of inflammation in gallbladder carcinogenesis obtained through epidemiological studies, genome-wide association studies, experimental carcinogenesis, morphogenetic studies and comparative studies with other inflammation-driven malignancies. The evidence strongly supports chronic, unresolved inflammation as the main carcinogenic mechanism of gallbladder cancer, regardless of the initial etiologic trigger. Given this central role of inflammation, evaluation of the potential for GBC prevention removing causes of inflammation or using anti-inflammatory drugs in high-risk populations may be warranted. PubMed","prediction_labels":"HUMAN"},{"cleaned":"conditional survival intrahepatic cholangiocarcinoma seer database analysis background conditional survival useful estimating survival probability patients survived one years initial diagnosis reflects possible change risk profile time especially malignancies poor outcome methods surveillance epidemiology end results database reviewed intrahepatic cholangiocarcinoma reviewed data intrahepatic cholangiocarcinoma year 2000 2010 data 8278 patients extracted seer database sub stratified using factors like age 50 versus 50 gender grade stage primary site surgery seer stat version 8 1 2 software used calculate conditional survival conditional survival defined calculated probability survival already survived specified number years diagnosis results analysis showed conditional survival cs probability intrahepatic cholangiocarcinoma increased 33 25 85 5 years age groups conditional surviving one year diagnoses age group 50 years cs increased 50 4 86 9 age group 50yrs 31 4 84 5 conditional survival well differentiated histology increased 60 7 81 0 moderately differentiated 53 8 87 7 poorly differentiated 37 1 83 6 conditional survival localized stage increased 50 7 88 8 regional 40 6 77 7 distant 19 0 65 6 majority cases missing data regard primary site surgery 1707 cases documented primary site surgery conditional survival group increased 30 7 82 8 subject surviving one year diagnosis conclusions several limitations associated results due missing data seer nonetheless results emphasize trend patient surviving 1 year diagnosis higher conditional survival probability cs may provide relevant prognostic information compared traditional survival estimates google scholar","probabilities":0.9799733,"Title":"Conditional Survival For Intrahepatic Cholangiocarcinoma: Seer Database Analysis","Abstract":"Background: Conditional survival can be useful for estimating survival probability for patients who have survived one or more years after the initial diagnosis. It reflects the possible change in risk profile over time especially for malignancies with poor outcome. Methods: The Surveillance, Epidemiology and End Results database was reviewed for intrahepatic cholangiocarcinoma. We reviewed data for all intrahepatic cholangiocarcinoma from year 2000-2010. Data of 8278 patients was extracted from SEER database. We sub stratified using factors like age <50 versus ≥50, gender, grade, stage, primary site surgery. SEER*Stat: Version *8.1.2 software was used to calculate conditional survival. Conditional survival is defined as the calculated probability of survival after having already survived a specified number of years from diagnosis. Results: The analysis showed that Conditional survival (CS) probability for intrahepatic cholangiocarcinoma increased from 33.25 to 85% at 5 years for all age groups conditional to surviving one year after diagnoses. For age group <50 years CS increased from 50.4% to 86.9%, while for age group >50yrs from 31.4% to 84.5%.The conditional survival for well differentiated histology increased from 60.7% to 81.0%, moderately differentiated from 53.8% to 87.7%, poorly differentiated from 37.1% to 83.6% .The conditional survival for localized stage increased from 50.7% to 88.8%, regional 40.6% to 77.7% and distant 19.0% to 65.6%.Majority of cases had missing data with regard to primary site surgery. 1707 cases had documented primary site surgery. Conditional survival for this group increased from 30.7% to 82.8% subject to surviving one year after diagnosis. Conclusions: There are several limitations associated with these results due to missing data in SEER. Nonetheless these results emphasize the trend of patient’s surviving more than 1 year after diagnosis have higher conditional survival probability. CS may provide more relevant prognostic information as compared to traditional survival estimates.","Source":"Google Scholar","category":"HUMAN","training_data":"Conditional Survival For Intrahepatic Cholangiocarcinoma: Seer Database Analysis Background: Conditional survival can be useful for estimating survival probability for patients who have survived one or more years after the initial diagnosis. It reflects the possible change in risk profile over time especially for malignancies with poor outcome. Methods: The Surveillance, Epidemiology and End Results database was reviewed for intrahepatic cholangiocarcinoma. We reviewed data for all intrahepatic cholangiocarcinoma from year 2000-2010. Data of 8278 patients was extracted from SEER database. We sub stratified using factors like age <50 versus ≥50, gender, grade, stage, primary site surgery. SEER*Stat: Version *8.1.2 software was used to calculate conditional survival. Conditional survival is defined as the calculated probability of survival after having already survived a specified number of years from diagnosis. Results: The analysis showed that Conditional survival (CS) probability for intrahepatic cholangiocarcinoma increased from 33.25 to 85% at 5 years for all age groups conditional to surviving one year after diagnoses. For age group <50 years CS increased from 50.4% to 86.9%, while for age group >50yrs from 31.4% to 84.5%.The conditional survival for well differentiated histology increased from 60.7% to 81.0%, moderately differentiated from 53.8% to 87.7%, poorly differentiated from 37.1% to 83.6% .The conditional survival for localized stage increased from 50.7% to 88.8%, regional 40.6% to 77.7% and distant 19.0% to 65.6%.Majority of cases had missing data with regard to primary site surgery. 1707 cases had documented primary site surgery. Conditional survival for this group increased from 30.7% to 82.8% subject to surviving one year after diagnosis. Conclusions: There are several limitations associated with these results due to missing data in SEER. Nonetheless these results emphasize the trend of patient’s surviving more than 1 year after diagnosis have higher conditional survival probability. CS may provide more relevant prognostic information as compared to traditional survival estimates. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"artesunate chloroquine induce cytotoxic activity cholangiocarcinoma cells via different cell death mechanisms chemotherapy cholangiocarcinoma cca quite successful study revisited possibility artesunate art chloroquine cq antimalarial drugs therapeutic agents cca possible mechanisms drugs exert cytotoxicity cca cells also explored effects art cq proliferation death patterns two cca cell lines kku 214 highly metastatic subtype kku 214l5 examined using water soluble tetrazolium wst assay time lapse photometry respectively differentiate verify death patterns necrosis apoptosis lactate dehydrogenase ldh release caspase 3 activity measured cellroxtm green reagent staining method used assess reactive oxygen species ros production art cq treated cells art cq significantly inhibited proliferation cca cells drugs kill malarial parasites via similar mechanism depending ros formation however art induced necrotic cell death cq induced apoptotic cell death cca cells art induced ldh release whereas cq activated caspase 3 confirming induction necrotic apoptotic cell deaths art cq respectively art treatment induced higher ros production cq art cq induce cca cells death via different death pathways art suitable necrosis sensitive cca whereas cq suitable apoptosis sensitive cca stn","probabilities":0.9467213,"Title":"Artesunate And Chloroquine Induce Cytotoxic Activity On Cholangiocarcinoma Cells Via Different Cell Death Mechanisms","Abstract":"Chemotherapy for cholangiocarcinoma (CCA) is not quite successful. In this study, we revisited the possibility of artesunate (ART) and chloroquine (CQ), the antimalarial drugs, as therapeutic agents against CCA. The possible mechanisms of these drugs to exert cytotoxicity on CCA cells were also explored. The effects of ART and CQ on proliferation and death patterns of two CCA cell lines, KKU-214 and its highly metastatic subtype KKU-214L5, were examined using water soluble tetrazolium (WST) assay and time-lapse photometry, respectively. To differentiate and verify the death patterns between necrosis and apoptosis, lactate dehydrogenase (LDH) release, and caspase 3 activity were measured. CellROXTM green reagent staining method was used to assess reactive oxygen species (ROS) production in ART- and CQ-treated cells. ART and CQ significantly inhibited proliferation of CCA cells. Both drugs kill malarial parasites via similar mechanism depending on ROS formation, however, ART induced necrotic cell death and CQ induced apoptotic cell death in CCA cells. ART induced LDH release, whereas CQ activated caspase 3, confirming induction of necrotic and apoptotic cell deaths by ART and CQ, respectively. ART treatment induced higher ROS production than CQ. ART and CQ induce CCA cells death via different death pathways. ART should be suitable for necrosis-sensitive CCA, whereas CQ is more suitable for apoptosis-sensitive CCA.","Source":"STN","category":"ANIMAL","training_data":"Artesunate And Chloroquine Induce Cytotoxic Activity On Cholangiocarcinoma Cells Via Different Cell Death Mechanisms Chemotherapy for cholangiocarcinoma (CCA) is not quite successful. In this study, we revisited the possibility of artesunate (ART) and chloroquine (CQ), the antimalarial drugs, as therapeutic agents against CCA. The possible mechanisms of these drugs to exert cytotoxicity on CCA cells were also explored. The effects of ART and CQ on proliferation and death patterns of two CCA cell lines, KKU-214 and its highly metastatic subtype KKU-214L5, were examined using water soluble tetrazolium (WST) assay and time-lapse photometry, respectively. To differentiate and verify the death patterns between necrosis and apoptosis, lactate dehydrogenase (LDH) release, and caspase 3 activity were measured. CellROXTM green reagent staining method was used to assess reactive oxygen species (ROS) production in ART- and CQ-treated cells. ART and CQ significantly inhibited proliferation of CCA cells. Both drugs kill malarial parasites via similar mechanism depending on ROS formation, however, ART induced necrotic cell death and CQ induced apoptotic cell death in CCA cells. ART induced LDH release, whereas CQ activated caspase 3, confirming induction of necrotic and apoptotic cell deaths by ART and CQ, respectively. ART treatment induced higher ROS production than CQ. ART and CQ induce CCA cells death via different death pathways. ART should be suitable for necrosis-sensitive CCA, whereas CQ is more suitable for apoptosis-sensitive CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"ercc1 advanced biliary tract cancer patients treated chemotherapy prognostic predictive roles background oncology tend look factors reflect better prognosis predict response treatments order make selection patients derive benefit avoiding futile therapies toxicities definitive prognostic predictive factors advanced biliary cancer remain unknown methods retrospectively analyzed consecutive patients institution advanced biliary tract cancer treated palliative cisplatin plus gemcitabine evaluated prognostic predictive role immunohistochemistry ihc expression ercc1 excision cross complementing gene 1 tumor response also examined several clinical laboratory prognostic factors overall survival results january 2009 july 2011 72 patients identified median overall survival 9 5 months independent variables associated shorter survival identified multivariable cox regression analysis ecog 2 3 hr 8 4 95 ci 3 4 20 7 p 0 001 charlson comorbidity index 1 hr 9 5 95 ci 1 6 55 3 p 0 012 pathology slides available 44 patients 23 52 stained positive ercc1 ihc score 0 5 subgroup expression ercc 1 prognostic associated either clinical benefit partial response stable disease tumor response partial response chemotherapy conclusions cohort unselected patients advanced biliary tract cancer treated first line gemcitabine plus cisplatin ihc expression ercc1 either predictive prognostic patients ecog 2 3 multiple comorbidities worse survival pubmed","probabilities":0.9799733,"Title":"ERCC1 in advanced biliary tract cancer patients treated with chemotherapy: prognostic and predictive roles","Abstract":"BACKGROUND: In oncology, we tend to look for factors that reflect better prognosis or predict response to treatments in order to make a selection from which patients will derive the benefit, avoiding futile therapies and/or toxicities. Definitive prognostic and predictive factors in advanced biliary cancer remain unknown. METHODS: We retrospectively analyzed all consecutive patients in our institution with advanced biliary tract cancer treated with palliative cisplatin plus gemcitabine. We evaluated the prognostic and predictive role of the immunohistochemistry (IHC) expression of ERCC1 (excision cross-complementing gene-1) on tumor response and also examined several clinical and laboratory prognostic factors for overall survival. RESULTS: From January 2009 to July 2011, 72 patients were identified; their median overall survival was 9.5 months. Independent variables associated with shorter survival identified by the multivariable Cox regression analysis were ECOG 2-3 (HR 8.4; 95% CI 3.4 to 20.7; p < 0.001) and Charlson Comorbidity Index >1 (HR 9.5; 95% CI 1.6 to 55.3; p = 0.012). Pathology slides were available from 44 patients: 23 (52%) stained positive for ERCC1 on IHC (score ≥0.5). In this subgroup, expression of ERCC-1 was not prognostic and was not associated with either clinical benefit (partial response and stable disease) or tumor response (partial response only) to chemotherapy. CONCLUSIONS: In this cohort of unselected patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin, IHC expression of ERCC1 was not either predictive or prognostic. Patients with ECOG 2-3 and/or multiple comorbidities had worse survival.","Source":"PubMed","category":"HUMAN","training_data":"ERCC1 in advanced biliary tract cancer patients treated with chemotherapy: prognostic and predictive roles BACKGROUND: In oncology, we tend to look for factors that reflect better prognosis or predict response to treatments in order to make a selection from which patients will derive the benefit, avoiding futile therapies and/or toxicities. Definitive prognostic and predictive factors in advanced biliary cancer remain unknown. METHODS: We retrospectively analyzed all consecutive patients in our institution with advanced biliary tract cancer treated with palliative cisplatin plus gemcitabine. We evaluated the prognostic and predictive role of the immunohistochemistry (IHC) expression of ERCC1 (excision cross-complementing gene-1) on tumor response and also examined several clinical and laboratory prognostic factors for overall survival. RESULTS: From January 2009 to July 2011, 72 patients were identified; their median overall survival was 9.5 months. Independent variables associated with shorter survival identified by the multivariable Cox regression analysis were ECOG 2-3 (HR 8.4; 95% CI 3.4 to 20.7; p < 0.001) and Charlson Comorbidity Index >1 (HR 9.5; 95% CI 1.6 to 55.3; p = 0.012). Pathology slides were available from 44 patients: 23 (52%) stained positive for ERCC1 on IHC (score ≥0.5). In this subgroup, expression of ERCC-1 was not prognostic and was not associated with either clinical benefit (partial response and stable disease) or tumor response (partial response only) to chemotherapy. CONCLUSIONS: In this cohort of unselected patients with advanced biliary tract cancer treated with first-line gemcitabine plus cisplatin, IHC expression of ERCC1 was not either predictive or prognostic. Patients with ECOG 2-3 and/or multiple comorbidities had worse survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment selection survival outcomes without radiation unresectable localized intrahepatic cholangiocarcinoma purpose patients intrahepatic cholangiocarcinoma present locally advanced disease amenable surgical resection inoperable patients chemotherapy alone generally considered standard care limited data regarding role radiotherapy used national cancer database investigate care patterns impact radiation component combined modality therapy overall survival methods queried national cancer database patients nonmetastatic intrahepatic cholangiocarcinoma diagnosed 2001 2011 undergoing surgery excluded included patients coded received chemotherapy kaplan meier overall survival estimates univariate multivariate cox proportional hazards regression analyses performed propensity score matched analysis performed account indication bias mitigate heterogeneity treatment groups results one thousand six hundred thirty six patients identified median follow 11 3 months median age 63 years 23 received combined modality therapy radiation two year overall survival entire cohort 21 chemotherapy alone combined modality therapy groups 20 versus 26 respectively univariate analysis overall survival improved combined modality therapy multivariate analysis combined modality therapy remained significantly associated improved overall survival younger age female sex higher median income lower comorbidity score earlier stage propensity score matched analysis confirmed overall survival benefit associated combined modality therapy discussion largest reported analysis combined modality therapy localized inoperable intrahepatic cholangiocarcinoma addition radiation chemotherapy associated improvement overall survival three quarters inoperable patients united states receive radiation survival remains relatively poor patients enthusiastically support ongoing randomized trials seeking incorporate radiotherapy possible means improve outcomes pubmed","probabilities":0.9799733,"Title":"Treatment Selection and Survival Outcomes With and Without Radiation for Unresectable, Localized Intrahepatic Cholangiocarcinoma","Abstract":"PURPOSE: Most patients with intrahepatic cholangiocarcinoma present with locally advanced disease not amenable to surgical resection. For these inoperable patients, chemotherapy alone is generally considered the standard of care, with limited data regarding the role of radiotherapy. We used the National Cancer Database to investigate care patterns and the impact of radiation as a component of combined modality therapy on overall survival. METHODS: We queried the National Cancer Database for patients with nonmetastatic intrahepatic cholangiocarcinoma diagnosed from 2001 to 2011. Those undergoing surgery were excluded. All included patients were coded as having received chemotherapy. Kaplan-Meier overall survival estimates and univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score-matched analysis was performed to account for indication bias and mitigate heterogeneity between treatment groups. RESULTS: One thousand six hundred thirty-six patients were identified with a median follow-up of 11.3 months. Median age was 63 years; 23% received combined modality therapy with radiation. Two-year overall survival for the entire cohort was 21%, and for the chemotherapy-alone and combined modality therapy groups, it was 20% versus 26%, respectively. On univariate analysis, overall survival was improved with combined modality therapy. On multivariate analysis, combined modality therapy remained significantly associated with improved overall survival, as did younger age, female sex, higher median income, lower comorbidity score, and earlier stage. Propensity score matched analysis confirmed the overall survival benefit associated with combined modality therapy. DISCUSSION: In this largest reported analysis of combined modality therapy for localized, inoperable intrahepatic cholangiocarcinoma, the addition of radiation to chemotherapy was associated with an improvement in overall survival. Three quarters of inoperable patients in the United States do not receive radiation. Survival remains relatively poor for all patients, and we enthusiastically support ongoing randomized trials seeking to incorporate radiotherapy as a possible means to improve outcomes.","Source":"PubMed","category":"HUMAN","training_data":"Treatment Selection and Survival Outcomes With and Without Radiation for Unresectable, Localized Intrahepatic Cholangiocarcinoma PURPOSE: Most patients with intrahepatic cholangiocarcinoma present with locally advanced disease not amenable to surgical resection. For these inoperable patients, chemotherapy alone is generally considered the standard of care, with limited data regarding the role of radiotherapy. We used the National Cancer Database to investigate care patterns and the impact of radiation as a component of combined modality therapy on overall survival. METHODS: We queried the National Cancer Database for patients with nonmetastatic intrahepatic cholangiocarcinoma diagnosed from 2001 to 2011. Those undergoing surgery were excluded. All included patients were coded as having received chemotherapy. Kaplan-Meier overall survival estimates and univariate and multivariate Cox proportional hazards regression analyses were performed. Propensity score-matched analysis was performed to account for indication bias and mitigate heterogeneity between treatment groups. RESULTS: One thousand six hundred thirty-six patients were identified with a median follow-up of 11.3 months. Median age was 63 years; 23% received combined modality therapy with radiation. Two-year overall survival for the entire cohort was 21%, and for the chemotherapy-alone and combined modality therapy groups, it was 20% versus 26%, respectively. On univariate analysis, overall survival was improved with combined modality therapy. On multivariate analysis, combined modality therapy remained significantly associated with improved overall survival, as did younger age, female sex, higher median income, lower comorbidity score, and earlier stage. Propensity score matched analysis confirmed the overall survival benefit associated with combined modality therapy. DISCUSSION: In this largest reported analysis of combined modality therapy for localized, inoperable intrahepatic cholangiocarcinoma, the addition of radiation to chemotherapy was associated with an improvement in overall survival. Three quarters of inoperable patients in the United States do not receive radiation. Survival remains relatively poor for all patients, and we enthusiastically support ongoing randomized trials seeking to incorporate radiotherapy as a possible means to improve outcomes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"papillary neoplasias biliary tract authors conducted revisional study intraepithelial papillary lesions bile ducts characterized kind rare intraductal growing cholangiocarcinoma articles published last 10 years reviewed authors considered adenoma carcinoma development important feature warrant prophylactic measures excisions histological type biomolecular behavior may relevance postoperative course lesions better prognosis compared histological types pubmed","probabilities":0.9799733,"Title":"Papillary neoplasias of the biliary tract","Abstract":"The authors conducted a revisional study of intraepithelial papillary lesions of the bile ducts, characterized by being a kind of rare, intraductal growing cholangiocarcinoma. Articles published in the last 10 years were reviewed. The authors considered that the adenoma-carcinoma development is an important feature to warrant prophylactic measures through excisions. The histological type and biomolecular behavior may have relevance in the postoperative course of such lesions, which have a better prognosis when compared with other histological types.","Source":"PubMed","category":"HUMAN","training_data":"Papillary neoplasias of the biliary tract The authors conducted a revisional study of intraepithelial papillary lesions of the bile ducts, characterized by being a kind of rare, intraductal growing cholangiocarcinoma. Articles published in the last 10 years were reviewed. The authors considered that the adenoma-carcinoma development is an important feature to warrant prophylactic measures through excisions. The histological type and biomolecular behavior may have relevance in the postoperative course of such lesions, which have a better prognosis when compared with other histological types. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative platelet lymphocyte ratio independent prognostic factor ampullary carcinoma following pancreaticoduodenectomy objective present study evaluate whether preoperative platelet lymphocyte ratio plr neutrophil lymphocyte ratio nlr predict prognosis curative resected ampullary carcinoma total 94 patients retrospectively included 6 year period consecutive cases underwent pancreaticoduodenectomy ampullary malignancy preoperative blood results available 94 cases resected ampullary carcinoma preoperative plr nlr cut values 226 8 2 58 determined represent optimal cut values cases survival analysis plr remained significant independent predictor survival multivariate analysis cox p 0 001 addition tumor differentiation p 0 001 nodal status p 0 001 stage p 0 001 nlr failed serve prognostic factor univariate p 0 0637 multivariate p 0 164 survival analysis furthermore nodal involvement rate higher high plr group 74 2 vs 19 05 p 0 001 preoperative plr nlr merit evaluation prognostic index curative resected ampullary carcinoma additionally candidate predictor lymph node metastasis stn","probabilities":0.9799733,"Title":"Preoperative Platelet-Lymphocyte Ratio Is An Independent Prognostic Factor In Ampullary Carcinoma Following Pancreaticoduodenectomy","Abstract":"The objective of the present study was to evaluate whether preoperative platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) could predict the prognosis for curative resected ampullary carcinoma. A total of 94 patients were retrospectively included over a 6-year period in which consecutive cases underwent pancreaticoduodenectomy for ampullary malignancy. Preoperative blood results were available in the 94 cases of resected ampullary carcinoma. Preoperative PLR and NLR cut-off values of 226.8 and 2.58 were determined to represent the optimal cut-off values in the cases for survival analysis. PLR remained a significant independent predictor of survival in multivariate analysis (Cox, P<0.001) in addition to tumor differentiation (P<0.001), nodal status (P<0.001) and stage (P<0.001). While NLR failed to serve as a prognostic factor in univariate (P=0.0637) and multivariate (P=0.164) survival analysis. Furthermore, the nodal involvement rate was higher in high PLR group (74.2 vs. 19.05%, P<0.001). Preoperative PLR and NLR merit further evaluation as a prognostic index in curative resected ampullary carcinoma. Additionally, it is a candidate predictor for the lymph node metastasis.","Source":"STN","category":"HUMAN","training_data":"Preoperative Platelet-Lymphocyte Ratio Is An Independent Prognostic Factor In Ampullary Carcinoma Following Pancreaticoduodenectomy The objective of the present study was to evaluate whether preoperative platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) could predict the prognosis for curative resected ampullary carcinoma. A total of 94 patients were retrospectively included over a 6-year period in which consecutive cases underwent pancreaticoduodenectomy for ampullary malignancy. Preoperative blood results were available in the 94 cases of resected ampullary carcinoma. Preoperative PLR and NLR cut-off values of 226.8 and 2.58 were determined to represent the optimal cut-off values in the cases for survival analysis. PLR remained a significant independent predictor of survival in multivariate analysis (Cox, P<0.001) in addition to tumor differentiation (P<0.001), nodal status (P<0.001) and stage (P<0.001). While NLR failed to serve as a prognostic factor in univariate (P=0.0637) and multivariate (P=0.164) survival analysis. Furthermore, the nodal involvement rate was higher in high PLR group (74.2 vs. 19.05%, P<0.001). Preoperative PLR and NLR merit further evaluation as a prognostic index in curative resected ampullary carcinoma. Additionally, it is a candidate predictor for the lymph node metastasis. STN","prediction_labels":"HUMAN"},{"cleaned":"alpha l fucosidase serves prognostic indicator intrahepatic cholangiocarcinoma inhibits invasion capacity alpha l fucosidase afu reported predictor survival patients several cancers unclear whether afu associated prognosis patients intrahepatic cholangiocarcinoma icca study used receiver operating characteristic roc analysis generate cutoff point afu overall survival os prognostic influence afu level serum os studied using kaplan meier curves moreover invasion assays western blotting performed explore effects afu icca invasion vitro found higher afu levels 20 85 u l significantly associated favorable median os 44 3 months versus 20 1 months p 0 022 icca patients cox regression models analyses showed afu level independent predictor os p 0 006 moreover results revealed afu impair invasion capability icca cells huh28 also downregulated expression matrix metalloproteinase 2 matrix metalloproteinase 9 conclusion results indicate afu significantly favorable prognostic factor icca patients pubmed","probabilities":0.5555556,"Title":"Alpha-L-Fucosidase Serves as a Prognostic Indicator for Intrahepatic Cholangiocarcinoma and Inhibits Its Invasion Capacity","Abstract":"Alpha-L-fucosidase (AFU) has been reported to be a predictor of survival in patients with several cancers, but it is unclear whether AFU is associated with prognosis in patients with intrahepatic cholangiocarcinoma (iCCA). In this study, we used receiver operating characteristic (ROC) analysis to generate the cutoff point of AFU for overall survival (OS). The prognostic influence of the AFU level in serum on OS was studied using Kaplan-Meier curves. Moreover, invasion assays and Western blotting were performed to explore the effects of AFU on iCCA invasion in vitro. We found that higher AFU levels (≥20.85 U/L) were significantly associated with favorable median OS (44.3 months versus 20.1 months; P = 0.022) in iCCA patients. Cox regression models' analyses showed that the AFU level was an independent predictor for OS (P = 0.006). Moreover, our results revealed that the AFU could impair the invasion capability of the iCCA cells, HuH28, and also downregulated the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. In conclusion, our results indicate that AFU is a significantly favorable prognostic factor in iCCA patients.","Source":"PubMed","category":"ANIMAL","training_data":"Alpha-L-Fucosidase Serves as a Prognostic Indicator for Intrahepatic Cholangiocarcinoma and Inhibits Its Invasion Capacity Alpha-L-fucosidase (AFU) has been reported to be a predictor of survival in patients with several cancers, but it is unclear whether AFU is associated with prognosis in patients with intrahepatic cholangiocarcinoma (iCCA). In this study, we used receiver operating characteristic (ROC) analysis to generate the cutoff point of AFU for overall survival (OS). The prognostic influence of the AFU level in serum on OS was studied using Kaplan-Meier curves. Moreover, invasion assays and Western blotting were performed to explore the effects of AFU on iCCA invasion in vitro. We found that higher AFU levels (≥20.85 U/L) were significantly associated with favorable median OS (44.3 months versus 20.1 months; P = 0.022) in iCCA patients. Cox regression models' analyses showed that the AFU level was an independent predictor for OS (P = 0.006). Moreover, our results revealed that the AFU could impair the invasion capability of the iCCA cells, HuH28, and also downregulated the expression of matrix metalloproteinase 2 and matrix metalloproteinase 9. In conclusion, our results indicate that AFU is a significantly favorable prognostic factor in iCCA patients. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"xiap antagonist embelin inhibited proliferation cholangiocarcinoma cells cholangiocarcinoma cells dependent antiapoptotic signaling survival resistance death stimuli recent mechanistic studies revealed increased cellular expression e3 ubiquitin protein ligase x linked inhibitor apoptosis xiap impairs trail chemotherapy induced cytotoxicity promoting survival cholangiocarcinoma cells study undertaken determine pharmacologic antagonism xiap protein sufficient sensitize cholangiocarcinoma cells cell death employed malignant cholangiocarcinoma cell lines used embelin antagonize xiap protein embelin treatment resulted decreased xiap protein levels 8 hours treatment maximal effect 16 hours kmch mz cha 1 cells assessment nuclear morphology demonstrated concentration dependent increase nuclear staining interestingly embelin induced nuclear morphology changes single agent independent addition tnf related apoptosis inducing ligand trail however caspase activity assays revealed increasing embelin concentrations resulted slight inhibition caspase activity activation addition use pan caspase inhibitor prevent nuclear morphology changes finally embelin treatment cholangiocarcinoma cells induce dna fragmentation parp cleavage apoptosis appear contribute effects embelin cholangiocarcinoma cells instead embelin caused inhibition cell proliferation cell cycle analysis indicated embelin increased number cells g2 m phase results demonstrate embelin decreased proliferation cholangiocarcinoma cell lines embelin treatment resulted decreased xiap protein expression induce enhance apoptosis thus cholangiocarcinoma cells mechanism action embelin may dependent apoptosis stn","probabilities":0.9467213,"Title":"Xiap Antagonist Embelin Inhibited Proliferation Of Cholangiocarcinoma Cells","Abstract":"Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP) impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 cells. Assessment of nuclear morphology demonstrated a concentration-dependent increase in nuclear staining. Interestingly, embelin induced nuclear morphology changes as a single agent, independent of the addition of TNF-related apoptosis inducing ligand (TRAIL). However, caspase activity assays revealed that increasing embelin concentrations resulted in slight inhibition of caspase activity, not activation. In addition, the use of a pan-caspase inhibitor did not prevent nuclear morphology changes. Finally, embelin treatment of cholangiocarcinoma cells did not induce DNA fragmentation or PARP cleavage. Apoptosis does not appear to contribute to the effects of embelin on cholangiocarcinoma cells. Instead, embelin caused inhibition of cell proliferation and cell cycle analysis indicated that embelin increased the number of cells in S and G2/M phase. Our results demonstrate that embelin decreased proliferation in cholangiocarcinoma cell lines. Embelin treatment resulted in decreased XIAP protein expression, but did not induce or enhance apoptosis. Thus, in cholangiocarcinoma cells the mechanism of action of embelin may not be dependent on apoptosis.","Source":"STN","category":"ANIMAL","training_data":"Xiap Antagonist Embelin Inhibited Proliferation Of Cholangiocarcinoma Cells Cholangiocarcinoma cells are dependent on antiapoptotic signaling for survival and resistance to death stimuli. Recent mechanistic studies have revealed that increased cellular expression of the E3 ubiquitin-protein ligase X-linked inhibitor of apoptosis (XIAP) impairs TRAIL- and chemotherapy-induced cytotoxicity, promoting survival of cholangiocarcinoma cells. This study was undertaken to determine if pharmacologic antagonism of XIAP protein was sufficient to sensitize cholangiocarcinoma cells to cell death. We employed malignant cholangiocarcinoma cell lines and used embelin to antagonize XIAP protein. Embelin treatment resulted in decreased XIAP protein levels by 8 hours of treatment with maximal effect at 16 hours in KMCH and Mz-ChA-1 cells. Assessment of nuclear morphology demonstrated a concentration-dependent increase in nuclear staining. Interestingly, embelin induced nuclear morphology changes as a single agent, independent of the addition of TNF-related apoptosis inducing ligand (TRAIL). However, caspase activity assays revealed that increasing embelin concentrations resulted in slight inhibition of caspase activity, not activation. In addition, the use of a pan-caspase inhibitor did not prevent nuclear morphology changes. Finally, embelin treatment of cholangiocarcinoma cells did not induce DNA fragmentation or PARP cleavage. Apoptosis does not appear to contribute to the effects of embelin on cholangiocarcinoma cells. Instead, embelin caused inhibition of cell proliferation and cell cycle analysis indicated that embelin increased the number of cells in S and G2/M phase. Our results demonstrate that embelin decreased proliferation in cholangiocarcinoma cell lines. Embelin treatment resulted in decreased XIAP protein expression, but did not induce or enhance apoptosis. Thus, in cholangiocarcinoma cells the mechanism of action of embelin may not be dependent on apoptosis. STN","prediction_labels":"ANIMAL"},{"cleaned":"benefit neoadjuvant concurrent chemoradiotherapy locally advanced perihilar cholangiocarcinoma aim clarify role neoadjuvant concurrent chemoradiotherapy naccrt followed surgical resection localized locally advanced perihilar cholangiocarcinoma cca methods retrospectively reviewed 57 patients underwent surgical resection without naccrt perihilar cca 12 patients received naccrt 45 patients received naccrt patients locally advanced perihilar cca requiring naccrt defined follows 1 mass involving unilateral branches portal vein hepatic artery insufficient volume anticipated remnant lobe 2 infiltrating mass main portal vein long reconstruction identified preoperative staging results median disease free survival dfs durations neoadjuvant non neoadjuvant ccrt groups 26 0 15 1 mo respectively p 0 91 median overall survival os durations neoadjuvant non neoadjuvant ccrt groups 32 9 27 1 mo respectively p 0 26 naccrt group showed downstaging tendency compared non naccrt group compared tumor stage confirmed histological examination surgery tumor stage confirmed imaging test time diagnosis p 0 01 conclusion naccrt prolong dfs os localized locally advanced perihilar cca however naccrt may allow tumor downstaging improve tumor resectability pubmed","probabilities":0.9799733,"Title":"Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma","Abstract":"AIM: To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA). METHODS: We retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging. RESULTS: The median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01). CONCLUSION: NACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability.","Source":"PubMed","category":"HUMAN","training_data":"Benefit of neoadjuvant concurrent chemoradiotherapy for locally advanced perihilar cholangiocarcinoma AIM: To clarify the role of neoadjuvant concurrent chemoradiotherapy (NACCRT) followed by surgical resection for localized or locally advanced perihilar cholangiocarcinoma (CCA). METHODS: We retrospectively reviewed 57 patients who underwent surgical resection with or without NACCRT for perihilar CCA; 12 patients received NACCRT and 45 patients did not received NACCRT. Patients with locally advanced perihilar CCA requiring NACCRT were defined as follows: (1) a mass involving unilateral branches of the portal vein or hepatic artery with insufficient volume of the anticipated remnant lobe; or (2) an infiltrating mass in the main portal vein that was too long for reconstruction, identified at preoperative staging. RESULTS: The median disease-free survival (DFS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 26.0 and 15.1 mo, respectively (P = 0.91). The median overall survival (OS) durations of the neoadjuvant and non-neoadjuvant CCRT groups were 32.9 and 27.1 mo, respectively (P = 0.26). The NACCRT group showed a downstaging tendency compared to the non-NACCRT group as compared with the tumor stage confirmed by histological examination after surgery and the tumor stage confirmed by imaging test at the time of diagnosis (P = 0.01). CONCLUSION: NACCRT does not prolong DFS and OS in localized or locally advanced perihilar CCA. However, NACCRT may allow tumor downstaging and improve tumor resectability. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gallbladder carcinoma prognostic factors therapeutic options outcome gallbladder carcinoma poor overall 5 year survival rate less 5 early stage disease 5 year survival rate 75 achieved stage adjusted therapy performed wide geographic variability frequency gallbladder carcinoma explained interaction genetic factors alteration gallstones chronic cholecystitis important risk factors formation gallbladder malignancies factors chronic bacterial infection primary sclerosing cholangitis anomalous junction pancreaticobiliary duct several types gallbladder polyps associated higher risk gallbladder cancer also interesting correlation risk factors histological type cancer however despite theoretical risk factors third gallbladder carcinomas recognized preoperatively patients tumor diagnosed pathologist routine cholecystectomy benign disease termed incidental occult gallbladder carcinoma igbc cholecystectomy performed frequently due minimal invasiveness laparoscopic technique therefore postoperative diagnosis potentially curable early stage disease frequent second radical re resection complete radical cholecystectomy required several igbcs however literature guidelines used different countries differ regarding radicality stage criteria performing radical cholecystectomy nccn guidelines data german registry gr records largest number incidental gallbladder carcinomas europe indicate carcinomas infiltrating muscularis propria beyond require radical surgery according gr data current literature wedge resection combined dissection lymph nodes hepatoduodenal ligament adequate t1b t2 carcinomas reason radical cholecystectomy simple ce formally r0 situation either occult invasion hepatic spread unknown lymphogenic dissemination unfortunately diverse interpretations practices regarding stage adjusted therapy gallbladder carcinoma current data suggest radical therapy warranted pubmed","probabilities":0.9799733,"Title":"Gallbladder carcinoma: Prognostic factors and therapeutic options","Abstract":"The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ''incidental or occult gallbladder carcinoma'' (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately, there are diverse interpretations and practices regarding stage-adjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder carcinoma: Prognostic factors and therapeutic options The outcome of gallbladder carcinoma is poor, and the overall 5-year survival rate is less than 5%. In early-stage disease, a 5-year survival rate up to 75% can be achieved if stage-adjusted therapy is performed. There is wide geographic variability in the frequency of gallbladder carcinoma, which can only be explained by an interaction between genetic factors and their alteration. Gallstones and chronic cholecystitis are important risk factors in the formation of gallbladder malignancies. Factors such as chronic bacterial infection, primary sclerosing cholangitis, an anomalous junction of the pancreaticobiliary duct, and several types of gallbladder polyps are associated with a higher risk of gallbladder cancer. There is also an interesting correlation between risk factors and the histological type of cancer. However, despite theoretical risk factors, only a third of gallbladder carcinomas are recognized preoperatively. In most patients, the tumor is diagnosed by the pathologist after a routine cholecystectomy for a benign disease and is termed ''incidental or occult gallbladder carcinoma'' (IGBC). A cholecystectomy is performed frequently due to the minimal invasiveness of the laparoscopic technique. Therefore, the postoperative diagnosis of potentially curable early-stage disease is more frequent. A second radical re-resection to complete a radical cholecystectomy is required for several IGBCs. However, the literature and guidelines used in different countries differ regarding the radicality or T-stage criteria for performing a radical cholecystectomy. The NCCN guidelines and data from the German registry (GR), which records the largest number of incidental gallbladder carcinomas in Europe, indicate that carcinomas infiltrating the muscularis propria or beyond require radical surgery. According to GR data and current literature, a wedge resection with a combined dissection of the lymph nodes of the hepatoduodenal ligament is adequate for T1b and T2 carcinomas. The reason for a radical cholecystectomy after simple CE in a formally R0 situation is either occult invasion or hepatic spread with unknown lymphogenic dissemination. Unfortunately, there are diverse interpretations and practices regarding stage-adjusted therapy for gallbladder carcinoma. The current data suggest that more radical therapy is warranted. PubMed","prediction_labels":"HUMAN"},{"cleaned":"staging laparoscopy hilar cholangiocarcinoma 100 patients purpose accurate preoperative radiological staging hilar cholangiocarcinoma remains difficult number patients found irresectable advanced tumours occult metastases exploration staging laparoscopy improve detection irresectable disease avoiding unnecessary laparotomy study examines role staging laparoscopy hilar cholangiocarcinoma focus yield different time periods identification preoperative factors increasing risk irresectable disease methods retrospective case note review patients undergoing staging laparoscopy radiologically resectable hilar cholangiocarcinoma identified hepatobiliary multidisciplinary team database performed results one hundred consecutive patients underwent staging laparoscopy 1998 2011 34 patients found irresectable due metastatic disease 11 due extensive local disease fifty patients proceeded exploratory laparotomy following staging laparoscopy 36 18 50 found irresectable disease 12 patients due advanced local disease 6 patients due metastases overall yield laparoscopy 45 accuracy 71 significant difference age preoperative bilirubin neutrophil lymphocyte ratio ca19 9 levels stage patients resectable disease irresectable disease laparoscopy also change yield laparoscopy time despite advances radiological imaging conclusion series staging laparoscopy avoided unnecessary laparotomy 45 patients radiologically resectable hilar cholangiocarcinoma factor able predict positive yield therefore patients potentially resectable hilar cholangiocarcinoma undergo staging laparoscopy google scholar","probabilities":0.9799733,"Title":"Staging Laparoscopy For Hilar Cholangiocarcinoma In 100 Patients","Abstract":"Purpose\nAccurate preoperative radiological staging of hilar cholangiocarcinoma remains difficult, and a number of patients are found to have irresectable advanced tumours or occult metastases at exploration. Staging laparoscopy can improve the detection of irresectable disease, avoiding unnecessary laparotomy. This study examines the role of staging laparoscopy in hilar cholangiocarcinoma, with a focus on yield over different time periods and identification of preoperative factors increasing the risk of irresectable disease.\nMethods\nRetrospective case note review of all patients undergoing staging laparoscopy for radiologically resectable hilar cholangiocarcinoma, identified from the hepatobiliary multidisciplinary team database, was performed.\nResults\nOne hundred consecutive patients underwent staging laparoscopy between 1998 and 2011. Of these, 34 patients were found to be irresectable due to metastatic disease, and 11, due to extensive local disease. Fifty patients proceeded to exploratory laparotomy following staging laparoscopy, and 36 % (18/50) of whom were found to have irresectable disease: 12 patients due to advanced local disease and 6 patients due to metastases. The overall yield of laparoscopy was 45 %, and the accuracy was 71 %.\nThere was no significant difference in age, preoperative bilirubin, neutrophil/lymphocyte ratio, Ca19-9 levels or T stage between patients with resectable disease and with irresectable disease on laparoscopy. There was also no change in the yield of laparoscopy over time, despite advances in radiological imaging.\nConclusion\nIn this series, staging laparoscopy avoided unnecessary laparotomy in 45 % of patients with radiologically resectable hilar cholangiocarcinoma. No factor was able to predict positive yield, and therefore, all patients with potentially resectable hilar cholangiocarcinoma should undergo staging laparoscopy.","Source":"Google Scholar","category":"HUMAN","training_data":"Staging Laparoscopy For Hilar Cholangiocarcinoma In 100 Patients Purpose\nAccurate preoperative radiological staging of hilar cholangiocarcinoma remains difficult, and a number of patients are found to have irresectable advanced tumours or occult metastases at exploration. Staging laparoscopy can improve the detection of irresectable disease, avoiding unnecessary laparotomy. This study examines the role of staging laparoscopy in hilar cholangiocarcinoma, with a focus on yield over different time periods and identification of preoperative factors increasing the risk of irresectable disease.\nMethods\nRetrospective case note review of all patients undergoing staging laparoscopy for radiologically resectable hilar cholangiocarcinoma, identified from the hepatobiliary multidisciplinary team database, was performed.\nResults\nOne hundred consecutive patients underwent staging laparoscopy between 1998 and 2011. Of these, 34 patients were found to be irresectable due to metastatic disease, and 11, due to extensive local disease. Fifty patients proceeded to exploratory laparotomy following staging laparoscopy, and 36 % (18/50) of whom were found to have irresectable disease: 12 patients due to advanced local disease and 6 patients due to metastases. The overall yield of laparoscopy was 45 %, and the accuracy was 71 %.\nThere was no significant difference in age, preoperative bilirubin, neutrophil/lymphocyte ratio, Ca19-9 levels or T stage between patients with resectable disease and with irresectable disease on laparoscopy. There was also no change in the yield of laparoscopy over time, despite advances in radiological imaging.\nConclusion\nIn this series, staging laparoscopy avoided unnecessary laparotomy in 45 % of patients with radiologically resectable hilar cholangiocarcinoma. No factor was able to predict positive yield, and therefore, all patients with potentially resectable hilar cholangiocarcinoma should undergo staging laparoscopy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"high dbc1 ccar2 expression gallbladder carcinoma associated favorable clinicopathological factors several studies gallbladder carcinogenesis mutations kras tp53 cdkn2a genes reported gallbladder carcinoma dbc1 gene deleted breast cancer 1 initially cloned region 8p21 homozygously deleted breast cancer dbc1 implicated cancer cell proliferation death functional role dbc1 normal cells role dbc1 loss cancer entirely clear dbc1 expression clinical implications gallbladder carcinoma yet thoroughly elucidated therefore evaluated dbc1 expression 104 gallbladder carcinoma tissues relation survival prognostic factors via immunohistochemical analysis dbc1 expression divided two categories high dbc1 expression observed 32 104 cases 30 8 low expression 72 104 cases 69 2 high dbc1 expression correlated significantly favorable clinicopathologic variables furthermore survival analysis high dbc1 expression group showed better survival rate compared low dbc1 expression group conclusion high dbc1 expression associated several favorable clinicopathologic factors gallbladder carcinoma findings suggest loss dbc1 expression plays role tumorigenesis tumor progression gallbladder carcinoma stn","probabilities":0.9467213,"Title":"High Dbc1 (Ccar2) Expression In Gallbladder Carcinoma Is Associated With Favorable Clinicopathological Factors","Abstract":"There have been several studies on gallbladder carcinogenesis, and mutations of the KRAS, TP53, and CDKN2A genes have been reported in gallbladder carcinoma. The DBC1 gene (deleted in breast cancer 1) was initially cloned from region 8p21, which was homozygously deleted in breast cancer. DBC1 has been implicated in cancer cell proliferation and death. The functional role of DBC1 in normal cells and the role of DBC1 loss in cancer are not entirely clear. And DBC1 expression and its clinical implications in gallbladder carcinoma have yet to be thoroughly elucidated. Therefore, we evaluated DBC1 expression in 104 gallbladder carcinoma tissues in relation to survival and other prognostic factors via immunohistochemical analysis. DBC1 expression was divided into two categories: high DBC1 expression was observed in 32/104 cases (30.8%) and low expression in 72/104 cases (69.2%). High DBC1 expression correlated significantly with favorable clinicopathologic variables. Furthermore, in survival analysis, the high-DBC1 expression group showed a better survival rate compared to the low-DBC1 expression group. In conclusion, high DBC1 expression is associated with several favorable clinicopathologic factors in gallbladder carcinoma. These findings suggest that loss of DBC1 expression plays a role in tumorigenesis and tumor progression in gallbladder carcinoma.","Source":"STN","category":"ANIMAL","training_data":"High Dbc1 (Ccar2) Expression In Gallbladder Carcinoma Is Associated With Favorable Clinicopathological Factors There have been several studies on gallbladder carcinogenesis, and mutations of the KRAS, TP53, and CDKN2A genes have been reported in gallbladder carcinoma. The DBC1 gene (deleted in breast cancer 1) was initially cloned from region 8p21, which was homozygously deleted in breast cancer. DBC1 has been implicated in cancer cell proliferation and death. The functional role of DBC1 in normal cells and the role of DBC1 loss in cancer are not entirely clear. And DBC1 expression and its clinical implications in gallbladder carcinoma have yet to be thoroughly elucidated. Therefore, we evaluated DBC1 expression in 104 gallbladder carcinoma tissues in relation to survival and other prognostic factors via immunohistochemical analysis. DBC1 expression was divided into two categories: high DBC1 expression was observed in 32/104 cases (30.8%) and low expression in 72/104 cases (69.2%). High DBC1 expression correlated significantly with favorable clinicopathologic variables. Furthermore, in survival analysis, the high-DBC1 expression group showed a better survival rate compared to the low-DBC1 expression group. In conclusion, high DBC1 expression is associated with several favorable clinicopathologic factors in gallbladder carcinoma. These findings suggest that loss of DBC1 expression plays a role in tumorigenesis and tumor progression in gallbladder carcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"autocrine requirement hedgehog signaling cholangiocarcinogenesis background aims hedgehog hh survival signalingpathway required progression cholangiocarcinoma cca highly desmoplastic cancer patient like preclini cal rodent model lethal malignancy however controversy regarding cellular targets hh signaling isunclear hh signaling inhibitors target tumor stromal cellsin microenvironment thereby indirectly reducing tumor pro gression inhibitors directly block hh signaling thecancer cells using syngeneic orthotopic rat ccamodel aim determine reducing hh signalingdirectly cancer cells tumor suppressive methods astable rat cca bdeneu cell line dominant negativepatched 1 blocks hh ligand dependent signaling wasgenerated using sleeping beauty transposon transfectionsystem following clonal selection constitutive inhibition thehh signaling verified reporter gene assay intrahep atic implantation wild type dominant negative patched 1transfected cells performed followed ipsilateral bile ductligation mimic cholestasis male adult fischer 344 rats 21days post implantation animals euthanized exam ined primary tumor characteristics presence metastaseswere recorded animal weight documented baseline 16 days post implantation time sacrifice results none animals implanted bdeneu cells domi nant negative patched 1 n 9 developed tumors contrast animals implanted wild type cca cells n 9 formedextremely aggressive tumors peritoneal 89 omental 89 diaphragmatic 55 metastases animals fromthe control wild type group systemic disease evidencedby appearance poor weight gain conclusion ananimal model cca cells constitutive inhibition hh sur vival signaling completely lacked ability establish tumors autocrine hh ligand survival signaling essential forcholangiocarcinoma development model google scholar","probabilities":0.9467213,"Title":"An Autocrine Requirement For Hedgehog Signaling In Cholangiocarcinogenesis","Abstract":"Background and Aims: The Hedgehog (Hh) survival signalingpathway is required for progression of cholangiocarcinoma(CCA), a highly desmoplastic cancer, in a patient-like, preclini-cal rodent model of this lethal malignancy. There is, however,controversy regarding the cellular targets of Hh signaling. It isunclear if Hh signaling inhibitors target the tumor stromal cellsin the microenvironment thereby indirectly reducing tumor pro-gression or if these inhibitors directly block Hh signaling in thecancer cells themselves. Using a syngeneic orthotopic rat CCAmodel, our aim was to determine if reducing Hh signalingdirectly in the cancer cells was tumor suppressive. Methods: Astable rat CCA BDEneu cell line with a dominant negativePatched-1, which blocks Hh ligand dependent signaling, wasgenerated using the Sleeping Beauty transposon transfectionsystem. Following clonal selection, constitutive inhibition of theHh signaling was verified by a reporter gene assay. Intrahep-atic implantation of wild-type or dominant negative Patched-1transfected cells was performed followed by ipsilateral bile ductligation to mimic cholestasis in male adult Fischer 344 rats. 21days post implantation animals were euthanized and exam-ined. Primary tumor characteristics and presence of metastaseswere recorded. Animal weight was documented at baseline,16 days post implantation, and at time of sacrifice. Results:None of the animals implanted with BDEneu cells with domi-nant negative Patched-1(n=9) developed tumors. In contrast,animals implanted with wild-type CCA cells (n=9) formedextremely aggressive tumors with peritoneal (89%), omental 89%), and diaphragmatic (55%) metastases. All animals fromthe control (wild-type) group had systemic disease as evidencedby their appearance and poor weight gain. Conclusion: In ananimal model, CCA cells with constitutive inhibition of Hh sur-vival signaling completely lacked the ability to establish tumors.An autocrine Hh ligand survival signaling is essential forcholangiocarcinoma development in this model","Source":"Google Scholar","category":"ANIMAL","training_data":"An Autocrine Requirement For Hedgehog Signaling In Cholangiocarcinogenesis Background and Aims: The Hedgehog (Hh) survival signalingpathway is required for progression of cholangiocarcinoma(CCA), a highly desmoplastic cancer, in a patient-like, preclini-cal rodent model of this lethal malignancy. There is, however,controversy regarding the cellular targets of Hh signaling. It isunclear if Hh signaling inhibitors target the tumor stromal cellsin the microenvironment thereby indirectly reducing tumor pro-gression or if these inhibitors directly block Hh signaling in thecancer cells themselves. Using a syngeneic orthotopic rat CCAmodel, our aim was to determine if reducing Hh signalingdirectly in the cancer cells was tumor suppressive. Methods: Astable rat CCA BDEneu cell line with a dominant negativePatched-1, which blocks Hh ligand dependent signaling, wasgenerated using the Sleeping Beauty transposon transfectionsystem. Following clonal selection, constitutive inhibition of theHh signaling was verified by a reporter gene assay. Intrahep-atic implantation of wild-type or dominant negative Patched-1transfected cells was performed followed by ipsilateral bile ductligation to mimic cholestasis in male adult Fischer 344 rats. 21days post implantation animals were euthanized and exam-ined. Primary tumor characteristics and presence of metastaseswere recorded. Animal weight was documented at baseline,16 days post implantation, and at time of sacrifice. Results:None of the animals implanted with BDEneu cells with domi-nant negative Patched-1(n=9) developed tumors. In contrast,animals implanted with wild-type CCA cells (n=9) formedextremely aggressive tumors with peritoneal (89%), omental 89%), and diaphragmatic (55%) metastases. All animals fromthe control (wild-type) group had systemic disease as evidencedby their appearance and poor weight gain. Conclusion: In ananimal model, CCA cells with constitutive inhibition of Hh sur-vival signaling completely lacked the ability to establish tumors.An autocrine Hh ligand survival signaling is essential forcholangiocarcinoma development in this model Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"potent antitumor activity liposomal irinotecan organoid crispr cas9 based murine model gallbladder cancer gallbladder cancer associated dismal prognosis accurate vivo models elemental improve understanding deadly disease develop better treatment options generated transplantation based murine model gallbladder cancer histologically mimics human disease including development distant metastasis murine gallbladder derived organoids genetically modified either retroviral transduction transfection crispr cas9 encoding plasmids thereby allowing rapid generation complex cancer genotypes characterize model presence two frequent oncogenic drivers kras erbb2 provide evidence tumor histology highly dependent driver oncogene demonstrate utility model preclinical assessment novel therapeutic approaches showing liposomal irinotecan nal iri retained tumor cells significantly prolongs survival gallbladder cancer bearing mice compared conventional irinotecan stn","probabilities":1.0,"Title":"Potent Antitumor Activity Of Liposomal Irinotecan In An Organoid-And Crispr-Cas9-Based Murine Model Of Gallbladder Cancer","Abstract":"Gallbladder cancer is associated with a dismal prognosis, and accurate in vivo models will be elemental to improve our understanding of this deadly disease and develop better treatment options. We have generated a transplantation-based murine model for gallbladder cancer that histologically mimics the human disease, including the development of distant metastasis. Murine gallbladder-derived organoids are genetically modified by either retroviral transduction or transfection with CRISPR/Cas9 encoding plasmids, thereby allowing the rapid generation of complex cancer genotypes. We characterize the model in the presence of two of the most frequent oncogenic drivers-Kras and ERBB2-and provide evidence that the tumor histology is highly dependent on the driver oncogene. Further, we demonstrate the utility of the model for the preclinical assessment of novel therapeutic approaches by showing that liposomal Irinotecan (Nal-IRI) is retained in tumor cells and significantly prolongs the survival of gallbladder cancer-bearing mice compared to conventional irinotecan.","Source":"STN","category":"ANIMAL","training_data":"Potent Antitumor Activity Of Liposomal Irinotecan In An Organoid-And Crispr-Cas9-Based Murine Model Of Gallbladder Cancer Gallbladder cancer is associated with a dismal prognosis, and accurate in vivo models will be elemental to improve our understanding of this deadly disease and develop better treatment options. We have generated a transplantation-based murine model for gallbladder cancer that histologically mimics the human disease, including the development of distant metastasis. Murine gallbladder-derived organoids are genetically modified by either retroviral transduction or transfection with CRISPR/Cas9 encoding plasmids, thereby allowing the rapid generation of complex cancer genotypes. We characterize the model in the presence of two of the most frequent oncogenic drivers-Kras and ERBB2-and provide evidence that the tumor histology is highly dependent on the driver oncogene. Further, we demonstrate the utility of the model for the preclinical assessment of novel therapeutic approaches by showing that liposomal Irinotecan (Nal-IRI) is retained in tumor cells and significantly prolongs the survival of gallbladder cancer-bearing mice compared to conventional irinotecan. STN","prediction_labels":"ANIMAL"},{"cleaned":"toxicology carcinogenesis studies 33 44 tetrachloroazobenzene tcab cas 14047 09 7 harlan sprague dawley rats b6c3f1 mice gavage studies 3 3 4 4 tetrachloroazobenzene tcab commercially manufactured formed unwanted product manufacture 3 4 dichloroaniline herbicidal derivatives propanil linuron diuron occurs degradation chloroanilide herbicides acylanilides phenylcarbamates phenylureas soil peroxide producing microorganisms formed photolysis biolysis 3 4 dichloroaniline humans may exposed tcab manufacture well application herbicides containing tcab contaminant tcab nominated united states environmental protection agency toxicity carcinogenicity testing based structural biological similarity 2 3 7 8 tetrachlorodibenzo p dioxin tcdd potential human exposure consumption crops contaminated 3 4 dichloroaniline derived herbicides male female harlan sprague dawley rats b6c3f1 mice administered tcab least 97 8 pure corn oil acetone 99 1 gavage 3 months rats 2 years 3 month study rats groups 10 male 10 female harlan sprague dawley rats administered 0 1 0 3 1 3 10 30 100 mg tcab kg body weight corn oil acetone 99 1 gavage 5 days week 14 weeks groups 10 male 10 female rats received corn oil acetone vehicle alone special study groups 30 dosed groups 6 vehicle control group female harlan sprague dawley rats administered 0 1 3 100 mg tcab kg body weight corn oil acetone 99 1 gavage 5 days week 13 weeks vehicle controls received corn oil acetone vehicle alone male female rats survived end study terminal mean body weights males significantly different vehicle controls group terminal mean body weights females administered 10 mg kg greater significantly less vehicle controls mean body weight gains dosed groups females significantly less vehicle controls hematology results indicate tcab induced microcytic normochromic responsive anemia male sprague dawley rats serum concentrations total thyroxine t4 free t4 significantly decreased dose related manner dosed groups sexes compared respective vehicle controls total triiodothyronine t3 thyroid stimulating hormone tsh concentrations generally unaffected statistically significant differences brdu labeling indices liver males females exposed tcab compared respective vehicle controls significant induction hepatic 7 ethoxyresorufin o deethylase erod 7 pentoxyresorufin o deethylase activities observed dosed groups males females significant induction hepatic acetanilide 4 hydroxylase activity observed males exposed 3 mg kg greater treated groups females erod activities lung generally increased increasing dose significantly greater treated groups males females compared respective vehicle controls highest concentrations tcab observed fat tissue lower concentrations liver lung tcab concentrations significantly increased dose dependent manner tissues dosed groups relative vehicle controls end 3 month study absolute relative liver weights significantly greater vehicle controls dosed groups males females administered 10 mg kg greater absolute relative lung weights significantly greater 100 mg kg males 3 mg kg greater females absolute relative right kidney spleen weights generally significantly greater dosed groups males absolute thymus weights 10 mg kg greater males absolute relative thymus weights 1 mg kg greater females significantly less vehicle controls liver incidences midzonal diffuse hepatocytic hypertrophy males administered 1 mg kg greater females administered 10 mg kg greater significantly greater vehicle control incidences hematopoietic cell proliferation occurred males administered 3 mg kg greater females administered 10 mg kg greater incidences midzonal hepatocytic cytoplasmic fatty vacuolization significantly increased males administered 3 mg kg greater lung significantly increased incidences bronchiolar metaplasia alveolar epithelium interstitial mononuclear cell infiltration occurred 10 30 100 mg kg males incidence interstitial mononuclear cell infiltration also significantly increased 100 mg kg females significantly increased incidences hematopoietic cell proliferation spleen occurred males administered 10 mg kg greater incidences hemosiderin pigment spleen significantly increased 10 mg kg greater females atrophy thymus significantly increased dosed groups females except 0 1 mg kg group males administered 10 mg kg greater 2 year study rats groups 50 male 50 female harlan sprague dawley rats administered 10 30 100 mg tcab kg body weight corn oil acetone 99 1 gavage 5 days week 2 years groups 50 male 50 female rats received corn oil acetone vehicle alone survival dosed groups males significantly less vehicle controls mean body weights 100 mg kg males less vehicle control group throughout study mean body weights 30 mg kg males 6 less vehicle control group week 24 10 mg kg males 7 less vehicle control group week 80 mean body weights 100 mg kg females less vehicle control group throughout study 30 mg kg females 6 less vehicle control group week 36 lung incidences multiple cystic keratinizing epithelioma single multiple cystic keratinizing epithelioma combined males females significantly increased dosed groups except multiple epithelioma 10 mg kg females significantly increased incidences pigmentation alveolar epithelium squamous metaplasia except 10 mg kg females alveolar epithelium bronchiolar metaplasia occurred dosed groups males females incidences histiocytic cellular infiltration dosed groups males significantly increased liver incidences cholangiocarcinoma single multiple occurred positive trend males significantly greater vehicle control group incidence 100 mg kg females also increased significant dose related increase hepatic toxicity observed dosed rats characterized increased incidences numerous lesions including hepatocyte hypertrophy centrilobular degeneration hepatocellular necrosis pigmentation fatty change bile duct hyperplasia oval cell hyperplasia nodular hyperplasia hematopoietic cell proliferation eosinophilic focus mixed cell focus multinucleated hepatocytes bile duct cyst toxic hepatopathy cholangiofibrosis significantly increased incidences gingival squamous cell carcinoma within oral mucosa occurred 10 mg kg males 100 mg kg males females incidences gingival squamous hyperplasia cystic keratinizing hyperplasia dosed groups males females generally significantly increased incidences follicular cell adenoma single multiple thyroid gland 30 100 mg kg males significantly greater vehicle control group incidences follicular cell hypertrophy follicular cell hyperplasia inflammation significantly increased 30 100 mg kg males three incidences single multiple squamous cell papilloma forestomach occurred 100 mg kg females single incidences squamous cell carcinoma forestomach occurred 10 100 mg kg females significantly increased incidences epithelial hyperplasia occurred dosed groups males females three incidences malignant schwanomma thoracic cavity 100 mg kg males single incidence 30 mg kg males adrenal cortex 30 100 mg kg females slightly increased incidences adenoma dosed groups males incidences degeneration cytoplasmic vacuolization hyperplasia zona fasciculata significantly increased increased incidences severities necrosis occurred 30 100 mg kg males incidences cytoplasmic vacuolation 10 100 mg kg females hyperplasia zona fasciculata 30 mg kg females significantly greater vehicle controls numerous nonneoplastic effects seen organs including atrophy acinar cytoplasmic vacuolization inflammation pancreas blood vessel inflammation lymphoid follicle atrophy pigmentation spleen pigmentation atrophy mesenteric lymph node germinal epithelial degeneration testes inflammation nose 2 year study mice groups 50 male 50 female mice administered 3 10 30 mg tcab kg body weight corn oil acetone 99 1 gavage 5 days week 2 years groups 50 male 50 female rats received corn oil acetone vehicle alone survival 10 30 mg kg males 30 mg kg females significantly less vehicle controls 30 mg kg males died end study abstract truncated stn","probabilities":0.9467213,"Title":"Toxicology And Carcinogenesis Studies Of 33'44'-Tetrachloroazobenzene (Tcab) (Cas No 14047-09-7) In Harlan Sprague-Dawley Rats And B6C3F1 Mice (Gavage Studies)","Abstract":"3,3',4,4'-Tetrachloroazobenzene (TCAB) is not commercially manufactured but is formed as an unwanted by-product in the manufacture of 3,4-dichloroaniline and its herbicidal derivatives Propanil, Linuron, and Diuron. It occurs from the degradation of chloroanilide herbicides (acylanilides, phenylcarbamates, and phenylureas) in soil by peroxide-producing microorganisms; and is formed by the photolysis and biolysis of 3,4-dichloroaniline. Humans may be exposed to TCAB during the manufacture as well as the application of herbicides containing TCAB as a contaminant. TCAB was nominated by the United States Environmental Protection Agency for toxicity and carcinogenicity testing based on its structural and biological similarity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the potential for human exposure from the consumption of crops contaminated with 3,4-dichloroaniline-derived herbicides. Male and female Harlan Sprague-Dawley rats and B6C3F1 mice were administered TCAB (at least 97.8% pure) in corn oil:acetone (99:1) by gavage for 3 months (rats only) or 2 years. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female Harlan Sprague-Dawley rats were administered 0.1, 0.3, 1, 3, 10, 30, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 14 weeks; groups of 10 male and 10 female rats received the corn oil:acetone vehicle alone. Special study groups of 30 (dosed groups) or 6 (vehicle control group) female Harlan Sprague-Dawley rats were administered 0.1, 3, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 13 weeks; vehicle controls received the corn oil:acetone vehicle alone. All male and female rats survived to the end of the study. Terminal mean body weights of males were not significantly different from vehicle controls in any group. Terminal mean body weights of females administered 10 mg/kg or greater were significantly less than those of the vehicle controls. Mean body weight gains of all dosed groups of females were significantly less than those of the vehicle controls. The hematology results indicate that TCAB induced a microcytic normochromic responsive anemia in male Sprague-Dawley rats. Serum concentrations of total thyroxine (T4) and free T4 were significantly decreased in a dose-related manner in all dosed groups in both sexes compared to their respective vehicle controls; total triiodothyronine (T3) and thyroid stimulating hormone (TSH) concentrations were generally unaffected. There were no statistically significant differences in the BrdU labeling indices in the liver of males or females exposed to TCAB compared to their respective vehicle controls. Significant induction of hepatic 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-deethylase activities was observed in all dosed groups of males and females. Significant induction of hepatic acetanilide-4-hydroxylase activity was observed in males exposed to 3 mg/kg or greater and all treated groups of females. EROD activities in the lung generally increased with increasing dose and were significantly greater in all treated groups of males and females compared to their respective vehicle controls. The highest concentrations of TCAB were observed in fat tissue with lower concentrations in the liver and lung. TCAB concentrations were significantly increased in a dose-dependent manner in all tissues from dosed groups relative to vehicle controls. At the end of the 3-month study, absolute and relative liver weights were significantly greater than those of the vehicle controls in all dosed groups of males and in females administered 10 mg/kg or greater. Absolute and relative lung weights were significantly greater in 100 mg/kg males and 3 mg/kg or greater females. Absolute and relative right kidney and spleen weights were generally significantly greater for all dosed groups of males. Absolute thymus weights of 10 mg/kg or greater males and absolute and relative thymus weights of 1 mg/kg or greater females were significantly less than those of the vehicle controls. In the liver, the incidences of midzonal to diffuse hepatocytic hypertrophy in males administered 1 mg/kg or greater and in females administered 10 mg/kg or greater were significantly greater than the vehicle control incidences. Hematopoietic cell proliferation occurred in most males administered 3 mg/kg or greater and most females administered 10 mg/kg or greater. The incidences of midzonal hepatocytic cytoplasmic fatty vacuolization were significantly increased in males administered 3 mg/kg or greater. In the lung, significantly increased incidences of bronchiolar metaplasia of the alveolar epithelium and interstitial mononuclear cell infiltration occurred in 10, 30, and 100 mg/kg males. The incidence of interstitial mononuclear cell infiltration was also significantly increased in 100 mg/kg females. Significantly increased incidences of hematopoietic cell proliferation of the spleen occurred in males administered 10 mg/kg or greater. The incidences of hemosiderin pigment of the spleen were significantly increased in 10 mg/kg or greater females. Atrophy in the thymus was significantly increased in all dosed groups of females, except the 0.1 mg/kg group, and in males administered 10 mg/kg or greater. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female Harlan Sprague-Dawley rats were administered 10, 30, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 2 years; groups of 50 male and 50 female rats received the corn oil:acetone vehicle alone. The survival of all dosed groups of males was significantly less than that of the vehicle controls. Mean body weights of 100 mg/kg males were less than those of the vehicle control group throughout the study. Mean body weights of 30 mg/kg males were 6% less than those of the vehicle control group after week 24, and those of 10 mg/kg males were 7% less than the vehicle control group after week 80. Mean body weights of 100 mg/kg females were less than those of the vehicle control group throughout the study, and those of 30 mg/kg females were 6% less than the vehicle control group after week 36. In the lung, the incidences of multiple cystic keratinizing epithelioma and single or multiple cystic keratinizing epithelioma (combined) in males and females were significantly increased in all dosed groups (except multiple epithelioma in 10 mg/kg females). Significantly increased incidences of pigmentation, alveolar epithelium squamous metaplasia (except 10 mg/kg females), and alveolar epithelium bronchiolar metaplasia occurred in all dosed groups of males and females. The incidences of histiocytic cellular infiltration in all dosed groups of males were significantly increased. In the liver, the incidences of cholangiocarcinoma (single or multiple) occurred in a positive trend in males and were significantly greater than that in the vehicle control group; the incidence in 100 mg/kg females was also increased. A significant dose-related increase in hepatic toxicity was observed in dosed rats and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, centrilobular degeneration, hepatocellular necrosis, pigmentation, fatty change, bile duct hyperplasia, oval cell hyperplasia, nodular hyperplasia, hematopoietic cell proliferation, eosinophilic focus, mixed cell focus, multinucleated hepatocytes, bile duct cyst, toxic hepatopathy, and cholangiofibrosis. Significantly increased incidences of gingival squamous cell carcinoma within the oral mucosa occurred in 10 mg/kg males and 100 mg/kg males and females. The incidences of gingival squamous hyperplasia and cystic keratinizing hyperplasia in dosed groups of males and females were generally significantly increased. The incidences of follicular cell adenoma (single or multiple) of the thyroid gland in 30 and 100 mg/kg males were significantly greater than that in the vehicle control group. The incidences of follicular cell hypertrophy, follicular cell hyperplasia, and inflammation were significantly increased in 30 and 100 mg/kg males. Three incidences of single or multiple squamous cell papilloma of the forestomach occurred in 100 mg/kg females, and single incidences of squamous cell carcinoma of the forestomach occurred in 10 and 100 mg/kg females. Significantly increased incidences of epithelial hyperplasia occurred in all dosed groups of males and females. There were three incidences of malignant schwanomma in the thoracic cavity in 100 mg/kg males and a single incidence in 30 mg/kg males. In the adrenal cortex of 30 and 100 mg/kg females, there were slightly increased incidences of adenoma. In all dosed groups of males, the incidences of degeneration, cytoplasmic vacuolization, and hyperplasia of the zona fasciculata were significantly increased. Increased incidences and severities of necrosis occurred in 30 and 100 mg/kg males. Incidences of cytoplasmic vacuolation in 10 and 100 mg/kg females and hyperplasia of the zona fasciculata in 30 mg/kg females were significantly greater than those in the vehicle controls. Numerous nonneoplastic effects were seen in other organs including atrophy, acinar cytoplasmic vacuolization, and inflammation of the pancreas; blood vessel inflammation; lymphoid follicle atrophy and pigmentation of the spleen; pigmentation and atrophy of the mesenteric lymph node; germinal epithelial degeneration of the testes; and inflammation of the nose. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered 3, 10, or 30 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 2 years; groups of 50 male and 50 female rats received the corn oil:acetone vehicle alone. Survival of 10 and 30 mg/kg males and 30 mg/kg females was significantly less than that of vehicle controls. All 30 mg/kg males died before the end of the study. (ABSTRACT TRUNCATED)","Source":"STN","category":"ANIMAL","training_data":"Toxicology And Carcinogenesis Studies Of 33'44'-Tetrachloroazobenzene (Tcab) (Cas No 14047-09-7) In Harlan Sprague-Dawley Rats And B6C3F1 Mice (Gavage Studies) 3,3',4,4'-Tetrachloroazobenzene (TCAB) is not commercially manufactured but is formed as an unwanted by-product in the manufacture of 3,4-dichloroaniline and its herbicidal derivatives Propanil, Linuron, and Diuron. It occurs from the degradation of chloroanilide herbicides (acylanilides, phenylcarbamates, and phenylureas) in soil by peroxide-producing microorganisms; and is formed by the photolysis and biolysis of 3,4-dichloroaniline. Humans may be exposed to TCAB during the manufacture as well as the application of herbicides containing TCAB as a contaminant. TCAB was nominated by the United States Environmental Protection Agency for toxicity and carcinogenicity testing based on its structural and biological similarity to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the potential for human exposure from the consumption of crops contaminated with 3,4-dichloroaniline-derived herbicides. Male and female Harlan Sprague-Dawley rats and B6C3F1 mice were administered TCAB (at least 97.8% pure) in corn oil:acetone (99:1) by gavage for 3 months (rats only) or 2 years. 3-MONTH STUDY IN RATS: Groups of 10 male and 10 female Harlan Sprague-Dawley rats were administered 0.1, 0.3, 1, 3, 10, 30, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 14 weeks; groups of 10 male and 10 female rats received the corn oil:acetone vehicle alone. Special study groups of 30 (dosed groups) or 6 (vehicle control group) female Harlan Sprague-Dawley rats were administered 0.1, 3, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 13 weeks; vehicle controls received the corn oil:acetone vehicle alone. All male and female rats survived to the end of the study. Terminal mean body weights of males were not significantly different from vehicle controls in any group. Terminal mean body weights of females administered 10 mg/kg or greater were significantly less than those of the vehicle controls. Mean body weight gains of all dosed groups of females were significantly less than those of the vehicle controls. The hematology results indicate that TCAB induced a microcytic normochromic responsive anemia in male Sprague-Dawley rats. Serum concentrations of total thyroxine (T4) and free T4 were significantly decreased in a dose-related manner in all dosed groups in both sexes compared to their respective vehicle controls; total triiodothyronine (T3) and thyroid stimulating hormone (TSH) concentrations were generally unaffected. There were no statistically significant differences in the BrdU labeling indices in the liver of males or females exposed to TCAB compared to their respective vehicle controls. Significant induction of hepatic 7-ethoxyresorufin-O-deethylase (EROD) and 7-pentoxyresorufin-O-deethylase activities was observed in all dosed groups of males and females. Significant induction of hepatic acetanilide-4-hydroxylase activity was observed in males exposed to 3 mg/kg or greater and all treated groups of females. EROD activities in the lung generally increased with increasing dose and were significantly greater in all treated groups of males and females compared to their respective vehicle controls. The highest concentrations of TCAB were observed in fat tissue with lower concentrations in the liver and lung. TCAB concentrations were significantly increased in a dose-dependent manner in all tissues from dosed groups relative to vehicle controls. At the end of the 3-month study, absolute and relative liver weights were significantly greater than those of the vehicle controls in all dosed groups of males and in females administered 10 mg/kg or greater. Absolute and relative lung weights were significantly greater in 100 mg/kg males and 3 mg/kg or greater females. Absolute and relative right kidney and spleen weights were generally significantly greater for all dosed groups of males. Absolute thymus weights of 10 mg/kg or greater males and absolute and relative thymus weights of 1 mg/kg or greater females were significantly less than those of the vehicle controls. In the liver, the incidences of midzonal to diffuse hepatocytic hypertrophy in males administered 1 mg/kg or greater and in females administered 10 mg/kg or greater were significantly greater than the vehicle control incidences. Hematopoietic cell proliferation occurred in most males administered 3 mg/kg or greater and most females administered 10 mg/kg or greater. The incidences of midzonal hepatocytic cytoplasmic fatty vacuolization were significantly increased in males administered 3 mg/kg or greater. In the lung, significantly increased incidences of bronchiolar metaplasia of the alveolar epithelium and interstitial mononuclear cell infiltration occurred in 10, 30, and 100 mg/kg males. The incidence of interstitial mononuclear cell infiltration was also significantly increased in 100 mg/kg females. Significantly increased incidences of hematopoietic cell proliferation of the spleen occurred in males administered 10 mg/kg or greater. The incidences of hemosiderin pigment of the spleen were significantly increased in 10 mg/kg or greater females. Atrophy in the thymus was significantly increased in all dosed groups of females, except the 0.1 mg/kg group, and in males administered 10 mg/kg or greater. 2-YEAR STUDY IN RATS: Groups of 50 male and 50 female Harlan Sprague-Dawley rats were administered 10, 30, or 100 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 2 years; groups of 50 male and 50 female rats received the corn oil:acetone vehicle alone. The survival of all dosed groups of males was significantly less than that of the vehicle controls. Mean body weights of 100 mg/kg males were less than those of the vehicle control group throughout the study. Mean body weights of 30 mg/kg males were 6% less than those of the vehicle control group after week 24, and those of 10 mg/kg males were 7% less than the vehicle control group after week 80. Mean body weights of 100 mg/kg females were less than those of the vehicle control group throughout the study, and those of 30 mg/kg females were 6% less than the vehicle control group after week 36. In the lung, the incidences of multiple cystic keratinizing epithelioma and single or multiple cystic keratinizing epithelioma (combined) in males and females were significantly increased in all dosed groups (except multiple epithelioma in 10 mg/kg females). Significantly increased incidences of pigmentation, alveolar epithelium squamous metaplasia (except 10 mg/kg females), and alveolar epithelium bronchiolar metaplasia occurred in all dosed groups of males and females. The incidences of histiocytic cellular infiltration in all dosed groups of males were significantly increased. In the liver, the incidences of cholangiocarcinoma (single or multiple) occurred in a positive trend in males and were significantly greater than that in the vehicle control group; the incidence in 100 mg/kg females was also increased. A significant dose-related increase in hepatic toxicity was observed in dosed rats and was characterized by increased incidences of numerous lesions including hepatocyte hypertrophy, centrilobular degeneration, hepatocellular necrosis, pigmentation, fatty change, bile duct hyperplasia, oval cell hyperplasia, nodular hyperplasia, hematopoietic cell proliferation, eosinophilic focus, mixed cell focus, multinucleated hepatocytes, bile duct cyst, toxic hepatopathy, and cholangiofibrosis. Significantly increased incidences of gingival squamous cell carcinoma within the oral mucosa occurred in 10 mg/kg males and 100 mg/kg males and females. The incidences of gingival squamous hyperplasia and cystic keratinizing hyperplasia in dosed groups of males and females were generally significantly increased. The incidences of follicular cell adenoma (single or multiple) of the thyroid gland in 30 and 100 mg/kg males were significantly greater than that in the vehicle control group. The incidences of follicular cell hypertrophy, follicular cell hyperplasia, and inflammation were significantly increased in 30 and 100 mg/kg males. Three incidences of single or multiple squamous cell papilloma of the forestomach occurred in 100 mg/kg females, and single incidences of squamous cell carcinoma of the forestomach occurred in 10 and 100 mg/kg females. Significantly increased incidences of epithelial hyperplasia occurred in all dosed groups of males and females. There were three incidences of malignant schwanomma in the thoracic cavity in 100 mg/kg males and a single incidence in 30 mg/kg males. In the adrenal cortex of 30 and 100 mg/kg females, there were slightly increased incidences of adenoma. In all dosed groups of males, the incidences of degeneration, cytoplasmic vacuolization, and hyperplasia of the zona fasciculata were significantly increased. Increased incidences and severities of necrosis occurred in 30 and 100 mg/kg males. Incidences of cytoplasmic vacuolation in 10 and 100 mg/kg females and hyperplasia of the zona fasciculata in 30 mg/kg females were significantly greater than those in the vehicle controls. Numerous nonneoplastic effects were seen in other organs including atrophy, acinar cytoplasmic vacuolization, and inflammation of the pancreas; blood vessel inflammation; lymphoid follicle atrophy and pigmentation of the spleen; pigmentation and atrophy of the mesenteric lymph node; germinal epithelial degeneration of the testes; and inflammation of the nose. 2-YEAR STUDY IN MICE: Groups of 50 male and 50 female mice were administered 3, 10, or 30 mg TCAB/kg body weight in corn oil:acetone (99:1) by gavage, 5 days a week, for 2 years; groups of 50 male and 50 female rats received the corn oil:acetone vehicle alone. Survival of 10 and 30 mg/kg males and 30 mg/kg females was significantly less than that of vehicle controls. All 30 mg/kg males died before the end of the study. (ABSTRACT TRUNCATED) STN","prediction_labels":"ANIMAL"},{"cleaned":"incidental carcinoma cholecystectomy benign disease gallbladder meta analysis study aimed determine incidence prognosis incidental carcinoma gallbladder igbc cholecystectomy meta analysis meta analysis included 51 studies 436 636 patients cholecystectomy incidence rate igbc cholecystectomy 0 6 95 confidence interval ci 0 5 0 8 incidence rate recent studies significantly different past studies mean age female ratio igbc subgroup significantly different overall patient group estimated rates igbc 13 0 34 1 39 7 22 7 12 5 ptis pt1 pt2 pt3 pt4 stages respectively patients igbc favorable overall survival rate compared patients non igbc hazard ratio hr 0 574 95 ci 0 445 0 739 however significant difference disease free survival igbc non igbc subgroups hr 0 931 95 ci 0 618 1 402 igbc found 0 6 patients cholecystectomy prognosis patients igbc favorable compared non igbc pathologic examination cholecystectomy benign diseases sufficient examination histology guaranteed detect igbc stn","probabilities":0.9799733,"Title":"Incidental Carcinoma After Cholecystectomy For Benign Disease Of The Gallbladder: A Meta-Analysis","Abstract":"This study aimed to determine the incidence and the prognosis of incidental carcinoma of the gallbladder (IGBC) after cholecystectomy through a meta-analysis. This meta-analysis included 51 studies and 436,636 patients with cholecystectomy. The incidence rate of IGBC after cholecystectomy was 0.6% (95% confidence interval (CI) 0.5%-0.8%). The incidence rate of recent studies was not significantly different from those of past studies. The mean age and female ratio of the IGBC subgroup were not significantly different from those of the overall patient group. The estimated rates of IGBC were 13.0%, 34.1%, 39.7%, 22.7%, and 12.5% in the pTis, pT1, pT2, pT3, and pT4 stages, respectively. Patients with IGBC had a favorable overall survival rate compared to patients with non-IGBC (hazard ratio (HR) 0.574, 95% CI 0.445-0.739). However, there was no significant difference of disease-free survival between the IGBC and non-IGBC subgroups (HR 0.931, 95% CI 0.618-1.402). IGBC was found in 0.6% of patients with cholecystectomy. The prognosis of patients with IGBC was favorable compared to those with non-IGBC. In the pathologic examination after cholecystectomy for benign diseases, a sufficient examination for histology should be guaranteed to detect IGBC.","Source":"STN","category":"HUMAN","training_data":"Incidental Carcinoma After Cholecystectomy For Benign Disease Of The Gallbladder: A Meta-Analysis This study aimed to determine the incidence and the prognosis of incidental carcinoma of the gallbladder (IGBC) after cholecystectomy through a meta-analysis. This meta-analysis included 51 studies and 436,636 patients with cholecystectomy. The incidence rate of IGBC after cholecystectomy was 0.6% (95% confidence interval (CI) 0.5%-0.8%). The incidence rate of recent studies was not significantly different from those of past studies. The mean age and female ratio of the IGBC subgroup were not significantly different from those of the overall patient group. The estimated rates of IGBC were 13.0%, 34.1%, 39.7%, 22.7%, and 12.5% in the pTis, pT1, pT2, pT3, and pT4 stages, respectively. Patients with IGBC had a favorable overall survival rate compared to patients with non-IGBC (hazard ratio (HR) 0.574, 95% CI 0.445-0.739). However, there was no significant difference of disease-free survival between the IGBC and non-IGBC subgroups (HR 0.931, 95% CI 0.618-1.402). IGBC was found in 0.6% of patients with cholecystectomy. The prognosis of patients with IGBC was favorable compared to those with non-IGBC. In the pathologic examination after cholecystectomy for benign diseases, a sufficient examination for histology should be guaranteed to detect IGBC. STN","prediction_labels":"HUMAN"},{"cleaned":"influence five potential anticancer drugs wnt pathway cell survival human biliary tract cancer cells background role wnt signalling carcinogenesis suggests compounds targeting pathway potential anti cancer drugs several studies report activation wnt signalling biliary tract cancer btc thus rendering wnt inhibitory drugs potential candidates targeted therapy highly chemoresistant disease methods study analysed five compounds suggested inhibitory effects wnt signalling dmat fh535 myricetin quercetin tbb cytotoxic efficiency mode cell death time cell line dependent characteristics well effects wnt pathway activity nine different btc cell lines results exposure cancer cells different concentrations compounds results clear dose dependent reduction viability drugs order fh535 dmat tbb myricetin quercetin first three substances show high cytotoxicity tested cell lines cause direct cytotoxic effect induction apoptosis inhibit pathway specific signal transduction wnt transcription factor reporter activity assay selected target genes growth promoting cyclin d1 cell cycle progression inhibitor p27 regulated treatment respectively conclusions taken together data demonstrate small molecular weight inhibitors dmat f535 tbb considerable cytotoxic possibly wnt specific effect btc cell lines vitro vivo investigation drugs well new wnt inhibitors may provide promising approach targeted therapy difficult treat tumour stn","probabilities":0.9467213,"Title":"Influence Of Five Potential Anticancer Drugs On Wnt Pathway And Cell Survival In Human Biliary Tract Cancer Cells","Abstract":"Background: The role of Wnt signalling in carcinogenesis suggests compounds targeting this pathway as potential anti-cancer drugs. Several studies report activation of Wnt signalling in biliary tract cancer (BTC) thus rendering Wnt inhibitory drugs as potential candidates for targeted therapy of this highly chemoresistant disease. \r\n\r\n Methods: In this study we analysed five compounds with suggested inhibitory effects on Wnt signalling (DMAT, FH535, myricetin, quercetin, and TBB) for their cytotoxic efficiency, mode of cell death, time- and cell line-dependent characteristics as well as their effects on Wnt pathway activity in nine different BTC cell lines. \r\n\r\n Results: Exposure of cancer cells to different concentrations of the compounds results in a clear dose-dependent reduction of viability for all drugs in the order FH535 > DMAT > TBB > myricetin > quercetin. The first three substances show high cytotoxicity in all tested cell lines, cause a direct cytotoxic effect by induction of apoptosis and inhibit pathway-specific signal transduction in a Wnt transcription factor reporter activity assay. Selected target genes such as growth-promoting cyclin D1 and the cell cycle progression inhibitor p27 are down- and up-regulated after treatment, respectively. \r\n\r\n Conclusions: Taken together, these data demonstrate that the small molecular weight inhibitors DMAT, F535 and TBB have a considerable cytotoxic and possibly Wnt-specific effect on BTC cell lines in vitro. Further in vivo investigation of these drugs as well as of new Wnt inhibitors may provide a promising approach for targeted therapy of this difficult-to-treat tumour.","Source":"STN","category":"ANIMAL","training_data":"Influence Of Five Potential Anticancer Drugs On Wnt Pathway And Cell Survival In Human Biliary Tract Cancer Cells Background: The role of Wnt signalling in carcinogenesis suggests compounds targeting this pathway as potential anti-cancer drugs. Several studies report activation of Wnt signalling in biliary tract cancer (BTC) thus rendering Wnt inhibitory drugs as potential candidates for targeted therapy of this highly chemoresistant disease. \r\n\r\n Methods: In this study we analysed five compounds with suggested inhibitory effects on Wnt signalling (DMAT, FH535, myricetin, quercetin, and TBB) for their cytotoxic efficiency, mode of cell death, time- and cell line-dependent characteristics as well as their effects on Wnt pathway activity in nine different BTC cell lines. \r\n\r\n Results: Exposure of cancer cells to different concentrations of the compounds results in a clear dose-dependent reduction of viability for all drugs in the order FH535 > DMAT > TBB > myricetin > quercetin. The first three substances show high cytotoxicity in all tested cell lines, cause a direct cytotoxic effect by induction of apoptosis and inhibit pathway-specific signal transduction in a Wnt transcription factor reporter activity assay. Selected target genes such as growth-promoting cyclin D1 and the cell cycle progression inhibitor p27 are down- and up-regulated after treatment, respectively. \r\n\r\n Conclusions: Taken together, these data demonstrate that the small molecular weight inhibitors DMAT, F535 and TBB have a considerable cytotoxic and possibly Wnt-specific effect on BTC cell lines in vitro. Further in vivo investigation of these drugs as well as of new Wnt inhibitors may provide a promising approach for targeted therapy of this difficult-to-treat tumour. STN","prediction_labels":"ANIMAL"},{"cleaned":"novel biomarker based preoperative prognostic grading system predicting survival surgery intrahepatic cholangiocarcinoma background although treatment strategies intrahepatic cholangiocarcinoma icc shifting towards multidisciplinary approaches preoperative radiographic methods identifying patients requiring therapy unclear study designed establish prognostic grading system using preoperatively available objective biomarkers methods novel preoperative prognostic grading system predicting survival surgery icc developed multivariate analysis 134 icc patients underwent surgery 1996 2015 using preoperatively available biomarkers results median overall survival time 3 5 year survival rates 33 3 months 48 38 respectively preoperative biomarkers neutrophil lymphocyte ratio 5 c reactive protein 5 mg l carbohydrate antigen 19 9 500 iu ml levels independently associated poor overall survival based presence factors preoperative prognostic grades defined follows grade 1 factor grade 2 one factor grade 3 two three factors median overall survival time 3 5 year survival rates patients grade 1 70 3 months 66 53 respectively higher patients grade 2 23 4 months 37 30 respectively p 0 004 grade 3 8 8 months 5 2 vs 3 p 0 001 multivariable analysis revealed preoperative prognostic grading system independently predicted survival adjusting known prognostic factors conclusions novel biomarker based preoperative prognostic grading system icc significantly stratifies survival surgery may identify patients requiring treatment stn","probabilities":0.9799733,"Title":"A Novel Biomarker-Based Preoperative Prognostic Grading System For Predicting Survival After Surgery For Intrahepatic Cholangiocarcinoma","Abstract":"Background: Although treatment strategies for intrahepatic cholangiocarcinoma (ICC) are shifting towards multidisciplinary approaches, preoperative radiographic methods for identifying patients requiring further therapy are unclear. This study was designed to establish a prognostic grading system using preoperatively available objective biomarkers. \r\n\r\n Methods: A novel preoperative prognostic grading system for predicting survival after surgery for ICC was developed from multivariate analysis of 134 ICC patients who underwent surgery between 1996 and 2015 using preoperatively available biomarkers. \r\n\r\n Results: The median overall survival time and 3- and 5 year survival rates were 33.3 months, 48, and 38%, respectively. Of the preoperative biomarkers, the neutrophil-to-lymphocyte ratio (≥5), and C-reactive protein (≥5 mg/L) and carbohydrate antigen 19-9 (≥500 IU/mL) levels were independently associated with poor overall survival. Based on the presence of these factors, the preoperative prognostic grades were defined as follows: grade 1, no factor; grade 2, one factor; and grade 3, two or three factors. The median overall survival time and 3- and 5 year survival rates of patients with grade 1 (70.3 months, 66, and 53%, respectively) were higher than those of patients with grade 2 (23.4 months, 37, and 30%, respectively; P = 0.004) and grade 3 (8.8 months, 5% both; 2 vs. 3, P < 0.001). Multivariable analysis revealed that the preoperative prognostic grading system independently predicted survival after adjusting for known prognostic factors. \r\n\r\n Conclusions: A novel biomarker-based preoperative prognostic grading system for ICC significantly stratifies survival after surgery and may identify patients requiring further treatment.","Source":"STN","category":"HUMAN","training_data":"A Novel Biomarker-Based Preoperative Prognostic Grading System For Predicting Survival After Surgery For Intrahepatic Cholangiocarcinoma Background: Although treatment strategies for intrahepatic cholangiocarcinoma (ICC) are shifting towards multidisciplinary approaches, preoperative radiographic methods for identifying patients requiring further therapy are unclear. This study was designed to establish a prognostic grading system using preoperatively available objective biomarkers. \r\n\r\n Methods: A novel preoperative prognostic grading system for predicting survival after surgery for ICC was developed from multivariate analysis of 134 ICC patients who underwent surgery between 1996 and 2015 using preoperatively available biomarkers. \r\n\r\n Results: The median overall survival time and 3- and 5 year survival rates were 33.3 months, 48, and 38%, respectively. Of the preoperative biomarkers, the neutrophil-to-lymphocyte ratio (≥5), and C-reactive protein (≥5 mg/L) and carbohydrate antigen 19-9 (≥500 IU/mL) levels were independently associated with poor overall survival. Based on the presence of these factors, the preoperative prognostic grades were defined as follows: grade 1, no factor; grade 2, one factor; and grade 3, two or three factors. The median overall survival time and 3- and 5 year survival rates of patients with grade 1 (70.3 months, 66, and 53%, respectively) were higher than those of patients with grade 2 (23.4 months, 37, and 30%, respectively; P = 0.004) and grade 3 (8.8 months, 5% both; 2 vs. 3, P < 0.001). Multivariable analysis revealed that the preoperative prognostic grading system independently predicted survival after adjusting for known prognostic factors. \r\n\r\n Conclusions: A novel biomarker-based preoperative prognostic grading system for ICC significantly stratifies survival after surgery and may identify patients requiring further treatment. STN","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma tumor burden prior tace value 3d quantitative analysis predict survival abstract available google scholar","probabilities":0.9799733,"Title":"Cholangiocarcinoma Tumor Burden Prior To Tace: The Value Of 3D Quantitative Analysis To Predict Survival","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Cholangiocarcinoma Tumor Burden Prior To Tace: The Value Of 3D Quantitative Analysis To Predict Survival Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance long non coding rna malat1 predicting recurrence metastasis gallbladder cancer effect cell proliferation migration invasion apoptosis objective study explore role malat1 molecular indicator predicting recurrence metastasis prognosis gallbladder cancer gbc effect proliferation invasion migration apoptosis gbc cells vitro gbc tissues adjacent normal tissues collected 102 patients malat1 short hairpin rna shrna plasmids first constructed transfect gbc sd cells reverse transcription quantitative polymerase chain reaction rt qpcr applied detect malat1 expression cck 8 assay flow cytometry transwell assay applied testify cell proliferation cell cycle apoptosis invasion migration receiver operating characteristic roc curve used evaluate values malat1 gbc recurrence metastasis prognosis cox regression analysis applied analyze independent influencing factors gbc patients survival status roc curve results showed malat1 expression predictor gbc recurrence metastasis prognosis according cox regression analysis malat1 expression tumor size tnm stage independent influencing factors gbc patients survival condition compared gbc sd cells transfected empty plasmids transfected malat1 shrna plasmids showed higher apoptosis rates weakened proliferation migration invasion conclusion findings demonstrate lncrna malat1 considered indicator evaluating recurrence metastasis prognosis gbc patients also demonstrate overexpression malat1 confers oncogenic function gbc google scholar","probabilities":0.9467213,"Title":"Prognostic Significance Of Long Non-Coding Rna Malat1 For Predicting The Recurrence And Metastasis Of Gallbladder Cancer And Its Effect On Cell Proliferation Migration Invasion And Apoptosis","Abstract":"The objective of this study is to explore the role of MALAT1 as a molecular indicator in predicting the recurrence, metastasis, and prognosis of gallbladder cancer (GBC) and its effect on the proliferation, invasion, migration, and apoptosis of GBC cells in vitro. GBC tissues and adjacent normal tissues were collected from 102 patients. MALAT1 short hairpin RNA (shRNA) plasmids were first constructed to transfect the GBC‐SD cells. Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) was applied to detect MALAT1 expression. CCK‐8 assay, flow cytometry, and Transwell assay were applied to testify the cell proliferation, cell cycle, apoptosis, invasion, and migration. A receiver operating characteristic (ROC) curve was used to evaluate the values of MALAT1 in GBC recurrence, metastasis, and prognosis. COX regression analysis was applied to analyze the independent influencing factors of GBC patients’ survival status. ROC curve results showed that the MALAT1 expression could be a predictor of the GBC recurrence, metastasis, and prognosis. According to the COX regression analysis, MALAT1 expression, tumor size, and TNM stage were independent influencing factors of GBC patients’ survival condition. Compared with the GBC‐SD cells transfected with empty plasmids, those transfected with MALAT1 shRNA plasmids showed higher apoptosis rates, weakened proliferation, migration, and invasion. In conclusion, our findings demonstrate that lncRNA MALAT1 can be considered as an indicator for evaluating the recurrence, metastasis, and prognosis of GBC patients. We also demonstrate how the overexpression of MALAT1 confers an oncogenic function in GBC.","Source":"Google Scholar","category":"ANIMAL","training_data":"Prognostic Significance Of Long Non-Coding Rna Malat1 For Predicting The Recurrence And Metastasis Of Gallbladder Cancer And Its Effect On Cell Proliferation Migration Invasion And Apoptosis The objective of this study is to explore the role of MALAT1 as a molecular indicator in predicting the recurrence, metastasis, and prognosis of gallbladder cancer (GBC) and its effect on the proliferation, invasion, migration, and apoptosis of GBC cells in vitro. GBC tissues and adjacent normal tissues were collected from 102 patients. MALAT1 short hairpin RNA (shRNA) plasmids were first constructed to transfect the GBC‐SD cells. Reverse transcription quantitative polymerase chain reaction (RT‐qPCR) was applied to detect MALAT1 expression. CCK‐8 assay, flow cytometry, and Transwell assay were applied to testify the cell proliferation, cell cycle, apoptosis, invasion, and migration. A receiver operating characteristic (ROC) curve was used to evaluate the values of MALAT1 in GBC recurrence, metastasis, and prognosis. COX regression analysis was applied to analyze the independent influencing factors of GBC patients’ survival status. ROC curve results showed that the MALAT1 expression could be a predictor of the GBC recurrence, metastasis, and prognosis. According to the COX regression analysis, MALAT1 expression, tumor size, and TNM stage were independent influencing factors of GBC patients’ survival condition. Compared with the GBC‐SD cells transfected with empty plasmids, those transfected with MALAT1 shRNA plasmids showed higher apoptosis rates, weakened proliferation, migration, and invasion. In conclusion, our findings demonstrate that lncRNA MALAT1 can be considered as an indicator for evaluating the recurrence, metastasis, and prognosis of GBC patients. We also demonstrate how the overexpression of MALAT1 confers an oncogenic function in GBC. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"family history cancer risk biliary tract cancers results biliary tract cancers pooling project background although familial cancer syndromes include biliary tract cancers btcs cancers gallbladder intrahepatic extrahepatic bile ducts ampulla vater studies examined relationships family history cancer fhc btcs reported inconclusive findings objective study investigate associations fhc risk btc biliary tract cancers pooling project bitcapp methods used cox proportional hazards regressions models estimate hrs 95 confidence intervals associations fhc first degree female relative male relative relative gastrointestinal cancer relative hormonally related cancer btc risk anatomic site within biliary tract adjusting sex race ethnicity sensitivity analyses conducted restricted studies reporting cholecystectomy data people without history cholecystectomy results data fhc available 12 prospective studies within bitcapp collectively contributed 2 246 cases 729 gallbladder 345 intrahepatic 615 extrahepatic bile duct 385 ampulla vater cancers 21 706 107 person years follow marginal inverse association fhc gallbladder cancer driven null analysis restricted studies reporting cholecystectomy data people without history cholecystectomy fhc associated risk btc anatomic sites conclusions findings support association fhc btcs impact study 1 5 million people fhc risk factor btcs cancer epidemiol biomarkers prev 27 3 348 51 2018 aacr pubmed","probabilities":0.9799733,"Title":"Family History of Cancer and Risk of Biliary Tract Cancers: Results from the Biliary Tract Cancers Pooling Project","Abstract":"Background: Although some familial cancer syndromes include biliary tract cancers (BTCs; cancers of the gallbladder, intrahepatic and extrahepatic bile ducts, and ampulla of Vater), the few studies that have examined the relationships between family history of cancer (FHC) and BTCs have reported inconclusive findings. The objective of this study was to investigate the associations of FHC with risk of BTC in the Biliary Tract Cancers Pooling Project (BiTCaPP).Methods: We used Cox proportional hazards regressions models to estimate HRs and 95% confidence intervals for associations between FHC (any, first-degree, in female relative, in male relative, relative with gastrointestinal cancer, and relative with hormonally related cancer) and BTC risk by anatomic site within the biliary tract, adjusting for sex and race/ethnicity. Sensitivity analyses were conducted that restricted to studies reporting cholecystectomy data and to people without a history of cholecystectomy.Results: Data on FHC were available from 12 prospective studies within BiTCaPP, which collectively contributed 2,246 cases (729 gallbladder, 345 intrahepatic and 615 extrahepatic bile duct, and 385 ampulla of Vater cancers) with 21,706,107 person-years of follow-up. A marginal, inverse association between FHC and gallbladder cancer was driven to the null when analysis was restricted to studies reporting cholecystectomy data and to people without a history of cholecystectomy. FHC was not associated with risk of BTC at the other anatomic sites.Conclusions: These findings do not support an association between FHC and BTCs.Impact: In a study of 1.5 million people, FHC is not a risk factor for BTCs. Cancer Epidemiol Biomarkers Prev; 27(3); 348-51. ©2018 AACR.","Source":"PubMed","category":"HUMAN","training_data":"Family History of Cancer and Risk of Biliary Tract Cancers: Results from the Biliary Tract Cancers Pooling Project Background: Although some familial cancer syndromes include biliary tract cancers (BTCs; cancers of the gallbladder, intrahepatic and extrahepatic bile ducts, and ampulla of Vater), the few studies that have examined the relationships between family history of cancer (FHC) and BTCs have reported inconclusive findings. The objective of this study was to investigate the associations of FHC with risk of BTC in the Biliary Tract Cancers Pooling Project (BiTCaPP).Methods: We used Cox proportional hazards regressions models to estimate HRs and 95% confidence intervals for associations between FHC (any, first-degree, in female relative, in male relative, relative with gastrointestinal cancer, and relative with hormonally related cancer) and BTC risk by anatomic site within the biliary tract, adjusting for sex and race/ethnicity. Sensitivity analyses were conducted that restricted to studies reporting cholecystectomy data and to people without a history of cholecystectomy.Results: Data on FHC were available from 12 prospective studies within BiTCaPP, which collectively contributed 2,246 cases (729 gallbladder, 345 intrahepatic and 615 extrahepatic bile duct, and 385 ampulla of Vater cancers) with 21,706,107 person-years of follow-up. A marginal, inverse association between FHC and gallbladder cancer was driven to the null when analysis was restricted to studies reporting cholecystectomy data and to people without a history of cholecystectomy. FHC was not associated with risk of BTC at the other anatomic sites.Conclusions: These findings do not support an association between FHC and BTCs.Impact: In a study of 1.5 million people, FHC is not a risk factor for BTCs. Cancer Epidemiol Biomarkers Prev; 27(3); 348-51. ©2018 AACR. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance survivin expression gallbladder carcinoma gallbladder cancers gbc characterized rapid progression early metastasis poor prognosis molecular mechanisms various signaling pathways involved elucidated develop effective therapies survivin apoptosis inhibitor protein expressed g2 m phase cell cycle plays role cell division affects cell survival proliferation survivin investigated many types cancer study aims examine relationship survivin expression gallbladder cancer patients clinicopathological features prognosis evaluated demographic characteristics age gender tumor characteristics histopathological type differentiation perineural lymphovascular invasion serosal invasion surgical margin positivity lymphocytic response survivin expression immunohistochemically analysed relationship characteristics prognosis 47 gallbladder carcinoma cases 2000 2011 immunohistochemically survivin expression observed 36 cases absent 11 cases follow data obtained 32 patients two 8 7 23 cases survivin positive tumor alive 74th 35th months whereas 5 55 6 nine cases survivin negative tumor alive 50th 89th 124th 126th 131th months survivin expression correlated short survival p 0 043 univariate analysis showed reduced overall survival associated age p 0 043 male gender p 0 038 infiltrative pattern p 0 019 lymphovascular invasion p 0 004 perineural invasion p 0 009 serosal invasion p 0 027 ulcer p 0 033 surgical margin positivity p 0 022 despite low number patients study analysis results suggest survivin positivity might actually significant prognostic factor finding reference point targeted treatment studies however studies involving broader series longer follow still required highly lethal gallbladder cancers pubmed","probabilities":0.962963,"Title":"The prognostic significance of survivin expression in gallbladder carcinoma","Abstract":"Gallbladder cancers (GBC) are characterized by rapid progression, early metastasis, and poor prognosis; the molecular mechanisms of the various signaling pathways involved should be elucidated to develop effective therapies. Survivin, an apoptosis inhibitor protein expressed in the G2/M phase of the cell cycle, plays a role in cell division and affects both cell survival and proliferation. Survivin has been investigated in many types of cancer, and this study aims to examine the relationship of survivin expression in gallbladder cancer patients with clinicopathological features and prognosis. We evaluated demographic characteristics (age, gender), tumor characteristics (histopathological type, differentiation, perineural, and lymphovascular invasion; serosal invasion, surgical margin positivity and lymphocytic response), and Survivin expression immunohistochemically, and we analysed the relationship between these characteristics and prognosis in 47 gallbladder carcinoma cases from 2000 to 2011. Immunohistochemically, while survivin expression was observed in 36 cases, it was absent in 11 cases. Follow-up data were obtained from 32 patients. Two (8.7%) of 23 cases with a Survivin-positive tumor were alive at 74th and 35th months, whereas 5 (%55.6) of nine cases with Survivin-negative tumor were alive at 50th, 89th, 124th, 126th, 131th months. Survivin expression was correlated with short survival (p = 0.043), and the univariate analysis showed that reduced overall survival was associated with age (p = 0.043), male gender (p = 0.038), infiltrative pattern (p = 0.019), lymphovascular invasion (p = 0.004), perineural invasion (p = 0.009), serosal invasion (p = 0.027), ulcer (p = 0.033), and surgical margin positivity (p = 0.022). Despite the low number of patients in our study, the analysis results suggest that survivin positivity might actually be a significant prognostic factor. This finding could be a reference point for targeted treatment studies. However, further studies involving broader series and longer follow-up are still required for highly lethal gallbladder cancers.","Source":"PubMed","category":"HUMAN","training_data":"The prognostic significance of survivin expression in gallbladder carcinoma Gallbladder cancers (GBC) are characterized by rapid progression, early metastasis, and poor prognosis; the molecular mechanisms of the various signaling pathways involved should be elucidated to develop effective therapies. Survivin, an apoptosis inhibitor protein expressed in the G2/M phase of the cell cycle, plays a role in cell division and affects both cell survival and proliferation. Survivin has been investigated in many types of cancer, and this study aims to examine the relationship of survivin expression in gallbladder cancer patients with clinicopathological features and prognosis. We evaluated demographic characteristics (age, gender), tumor characteristics (histopathological type, differentiation, perineural, and lymphovascular invasion; serosal invasion, surgical margin positivity and lymphocytic response), and Survivin expression immunohistochemically, and we analysed the relationship between these characteristics and prognosis in 47 gallbladder carcinoma cases from 2000 to 2011. Immunohistochemically, while survivin expression was observed in 36 cases, it was absent in 11 cases. Follow-up data were obtained from 32 patients. Two (8.7%) of 23 cases with a Survivin-positive tumor were alive at 74th and 35th months, whereas 5 (%55.6) of nine cases with Survivin-negative tumor were alive at 50th, 89th, 124th, 126th, 131th months. Survivin expression was correlated with short survival (p = 0.043), and the univariate analysis showed that reduced overall survival was associated with age (p = 0.043), male gender (p = 0.038), infiltrative pattern (p = 0.019), lymphovascular invasion (p = 0.004), perineural invasion (p = 0.009), serosal invasion (p = 0.027), ulcer (p = 0.033), and surgical margin positivity (p = 0.022). Despite the low number of patients in our study, the analysis results suggest that survivin positivity might actually be a significant prognostic factor. This finding could be a reference point for targeted treatment studies. However, further studies involving broader series and longer follow-up are still required for highly lethal gallbladder cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"neuroendocrine tumors extrahepatic biliary tract neuroendocrine tumors extrahepatic bile ducts ebnets rare aim present review elucidate characteristics ebnets treatment prognosis exhaustive systematic review literature performed 1959 date one hundred articles describing 150 cases collected article carefully analyzed database created common symptoms jaundice 60 3 pruritus 19 2 cholelithiasis co existed 15 cases 19 2 hormone vasoactive peptide related symptoms present 7 cases 9 frequent sites found common hepatic duct proximal common bile duct 19 2 surgical management considered main treatment ebnets excision extrahepatic biliary tree 62 82 portal vein lymphadenectomy 43 6 popular procedure ebnets extremely rare rarity makes characterization particularly difficult date final diagnosis made surgery pathology immunohistochemistry findings present analysis existing published cases elucidates many aspects tumours giving complete clinicopathological documentation pubmed","probabilities":0.9799733,"Title":"Neuroendocrine tumors of extrahepatic biliary tract","Abstract":"Neuroendocrine tumors of the extrahepatic bile ducts (EBNETs) are very rare. The aim of the present review is to elucidate the characteristics of EBNETs, their treatment and prognosis. An exhaustive systematic review of the literature was performed from 1959 up-to-date. One hundred articles, describing 150 cases were collected. Each article was carefully analyzed and a database was created. The most common symptoms were jaundice (60.3 %) and pruritus (19.2 %). Cholelithiasis co-existed in 15 cases (19.2 %). Hormone- and vasoactive peptide- related symptoms were present in only 7 cases (9 %). The most frequent sites were found to be the common hepatic duct and the proximal common bile duct (19.2 %). Surgical management was considered the main treatment for EBNETs, while excision of extrahepatic biliary tree (62.82 %) with portal vein lymphadenectomy (43.6 %) was the most popular procedure. EBNETs are extremely rare. Their rarity makes their characterization particularly difficult. Up to date the final diagnosis is made after surgery by pathology and immunohistochemistry findings. The present analysis of the existing published cases elucidates many aspects of these tumours, giving complete clinicopathological documentation.","Source":"PubMed","category":"HUMAN","training_data":"Neuroendocrine tumors of extrahepatic biliary tract Neuroendocrine tumors of the extrahepatic bile ducts (EBNETs) are very rare. The aim of the present review is to elucidate the characteristics of EBNETs, their treatment and prognosis. An exhaustive systematic review of the literature was performed from 1959 up-to-date. One hundred articles, describing 150 cases were collected. Each article was carefully analyzed and a database was created. The most common symptoms were jaundice (60.3 %) and pruritus (19.2 %). Cholelithiasis co-existed in 15 cases (19.2 %). Hormone- and vasoactive peptide- related symptoms were present in only 7 cases (9 %). The most frequent sites were found to be the common hepatic duct and the proximal common bile duct (19.2 %). Surgical management was considered the main treatment for EBNETs, while excision of extrahepatic biliary tree (62.82 %) with portal vein lymphadenectomy (43.6 %) was the most popular procedure. EBNETs are extremely rare. Their rarity makes their characterization particularly difficult. Up to date the final diagnosis is made after surgery by pathology and immunohistochemistry findings. The present analysis of the existing published cases elucidates many aspects of these tumours, giving complete clinicopathological documentation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"improved survival national cohort resected distal cholangiocarcinoma treated adjuvant therapy introduction data efficacy adjuvant therapy distal cholangiocarcinoma limited absence randomized clinical trials aim study determine subgroups following surgically resected distal cholangiocarcinoma adjuvant therapy efficacious methods conducted retrospective analysis ncbd patients diagnosed surgically resected distal cholangiocarcinoma 2006 2013 patients received adjuvant therapy observation ob included analysis 90 day mortality excluded minimize immortal time bias patients received adjuvant therapy matched observation ob propensity score minimize selection bias results 1 782 patients identified surgically resected distal cholangiocarcinoma 840 patients 47 ob group 942 53 group group younger p 0 001 less comorbidities charlson deyo score p 0 001 likely private insurance p 0 001 group also likely t3 t4 disease 72 vs 57 p 0 001 n1 n2 disease 58 vs 37 p 0 001 positive surgical margins 26 vs 16 p 0 001 1 1 propensity score matching 500 ob patients compared 500 patients receipt associated better overall survival compared ob group hr 0 79 95 ci 0 67 0 93 median overall survival 31 2 months group 25 2 months observation group p value 0 006 1 3 5 year survival 87 46 31 group 79 39 24 ob group subgroup analysis showed survival advantage evident t3 t4 disease hr 0 72 95 ci 0 59 0 89 node positive disease hr 0 70 95 ci 0 56 0 87 positive resection margin hr 0 58 95 ci 0 420 81 conclusions adjuvant therapy associated improved overall survival resected distal cholangiocarcinoma especially t3 t4 disease node positive disease positive resection margin study supports use adjuvant therapy high risk patients google scholar","probabilities":0.9799733,"Title":"Improved Survival In A National Cohort Of Resected Distal Cholangiocarcinoma Treated With Adjuvant Therapy","Abstract":"Introduction: The data on the efficacy of adjuvant therapy in distal cholangiocarcinoma is limited in the absence of randomized clinical trials. The aim of this study was to determine in what subgroups following surgically resected distal cholangiocarcinoma would adjuvant therapy be efficacious. Methods: We conducted a retrospective analysis of NCBD of patients diagnosed with surgically resected distal cholangiocarcinoma between 2006 and 2013. All patients who received adjuvant therapy (AT) or observation (OB) were included for analysis. 90-day mortality was excluded to minimize immortal time bias. Patients who received adjuvant therapy (AT) were matched to observation (OB) by propensity score to minimize selection bias. Results: Of the 1,782 patients identified with surgically resected distal cholangiocarcinoma, 840 patients (47%) were in the OB group and 942 (53%) in the AT group. The AT group was younger (p<0.001), had less comorbidities by Charlson-Deyo score (p<0.001), and was more likely to have private insurance (p<0.001). The AT group also was more likely to have T3/T4 disease (72% vs. 57%, p<0.001), N1/N2 disease (58% vs. 37%, p<0.001) and positive surgical margins (26% vs. 16%, p<0.001). After 1:1 propensity score matching, 500 OB patients were compared to 500 AT patients. The receipt of AT was associated with better overall survival compared to the OB group (HR=0.79; 95% CI:0.67-0.93). The median overall survival was 31.2 months for the AT group and 25.2 months for the observation group (P value = 0.006). The 1-, 3-, and 5-year survival were 87%, 46%, and 31% for the AT group; 79%, 39% and 24% for OB group. Subgroup analysis showed that the survival advantage for AT was evident in T3/T4 disease (HR=0.72; 95% CI:0.59-0.89), node positive disease (HR=0.70; 95% CI:0.56-0.87) and positive resection margin (HR=0.58; 95% CI:0.420.81). Conclusions: Adjuvant therapy is associated with improved overall survival in resected distal cholangiocarcinoma, especially in T3/T4 disease, node positive disease and positive resection margin. This study supports the use of adjuvant therapy in high-risk patients.","Source":"Google Scholar","category":"HUMAN","training_data":"Improved Survival In A National Cohort Of Resected Distal Cholangiocarcinoma Treated With Adjuvant Therapy Introduction: The data on the efficacy of adjuvant therapy in distal cholangiocarcinoma is limited in the absence of randomized clinical trials. The aim of this study was to determine in what subgroups following surgically resected distal cholangiocarcinoma would adjuvant therapy be efficacious. Methods: We conducted a retrospective analysis of NCBD of patients diagnosed with surgically resected distal cholangiocarcinoma between 2006 and 2013. All patients who received adjuvant therapy (AT) or observation (OB) were included for analysis. 90-day mortality was excluded to minimize immortal time bias. Patients who received adjuvant therapy (AT) were matched to observation (OB) by propensity score to minimize selection bias. Results: Of the 1,782 patients identified with surgically resected distal cholangiocarcinoma, 840 patients (47%) were in the OB group and 942 (53%) in the AT group. The AT group was younger (p<0.001), had less comorbidities by Charlson-Deyo score (p<0.001), and was more likely to have private insurance (p<0.001). The AT group also was more likely to have T3/T4 disease (72% vs. 57%, p<0.001), N1/N2 disease (58% vs. 37%, p<0.001) and positive surgical margins (26% vs. 16%, p<0.001). After 1:1 propensity score matching, 500 OB patients were compared to 500 AT patients. The receipt of AT was associated with better overall survival compared to the OB group (HR=0.79; 95% CI:0.67-0.93). The median overall survival was 31.2 months for the AT group and 25.2 months for the observation group (P value = 0.006). The 1-, 3-, and 5-year survival were 87%, 46%, and 31% for the AT group; 79%, 39% and 24% for OB group. Subgroup analysis showed that the survival advantage for AT was evident in T3/T4 disease (HR=0.72; 95% CI:0.59-0.89), node positive disease (HR=0.70; 95% CI:0.56-0.87) and positive resection margin (HR=0.58; 95% CI:0.420.81). Conclusions: Adjuvant therapy is associated with improved overall survival in resected distal cholangiocarcinoma, especially in T3/T4 disease, node positive disease and positive resection margin. This study supports the use of adjuvant therapy in high-risk patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"efficacy safety folfirinox advanced cholangiocarcinoma background cholangiocarcinomas invasive carcinomas uncommon diagnosis often diagnosed advanced metastatic stage date limited clinical data support standard chemotherapy regimen single agent systemic chemotherapy 5fu gemcitabine achieves orr 25 combination regimens including 5 fu adriamycin mitomycin 5 fu cisplatin os less year methods conducted single institution retrospective analysis survival response toxicity patients advanced metastatic hepatobiliary carcinoma treated fluoropyrimidine irinotecan oxaliplatin combination therapy october 2008 may 2015 primary endpoint pfs measured date first treatment evidence clinical progression death secondary endpoint toxicity based national cancer institute common terminology criteria adverse events nci ctcae non hematologic hematologic toxicity patients age greater equal 18 histologically confirmed locally advanced unresectable metastatic adenocarcinoma biliary tract intrahepatic extrahepatic cholangiocarcinoma treatment naive one prior chemotherapy ecog performance status 0 2 results twenty five patients eligible analysis total six patients 24 received folfirinox either first line therapy second line therapy progression gemcitabine based regimen median pfs 5 months 151 days median os 14 5 months 436 days frequency hematologic toxicity common non hematologic toxicity thrombocytopenia 67 nausea 67 common adverse event treatment related death recorded patients discontinued therapy due disease progression conclusions single institution retrospective outcome analysis folfirinox shown activity maintaining disease control either first second line therapy advanced cholangiocarcinoma hematologic non hematologic side effects frequent manageable without significant treatment delay discontinuation treatment related deaths google scholar","probabilities":0.9799733,"Title":"Efficacy And Safety Of Folfirinox In Advanced Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinomas are invasive carcinomas of uncommon diagnosis and often diagnosed at an advanced and metastatic stage. To this date, there is limited clinical data to support a standard chemotherapy regimen. Single agent systemic chemotherapy such as 5FU or gemcitabine achieves ORR of about 25% while combination regimens including 5-FU, adriamycin, mitomycin or 5-FU and cisplatin has OS of less than a year. Methods: We conducted a single institution retrospective analysis of survival, response and toxicity in patients with advanced or metastatic hepatobiliary carcinoma who had been treated with fluoropyrimidine, irinotecan, and oxaliplatin combination therapy from October 2008 to May 2015. Primary endpoint was PFS measured as the date of first treatment until evidence of clinical progression and/or death. Secondary endpoint was toxicity based on National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE) for non hematologic and hematologic toxicity. Patients were age greater or equal to 18, histologically confirmed, locally advanced unresectable or metastatic adenocarcinoma of the biliary tract (intrahepatic or extrahepatic cholangiocarcinoma), treatment naive or one prior chemotherapy, ECOG performance status of 0-2. Results: Twenty-five patients were eligible for analysis. A total of six patients (24%) received FOLFIRINOX either as first line therapy or as a second line therapy after progression on gemcitabine based regimen. The median PFS was 5 months (151 days). The median OS was about 14.5 months (436 days). Frequency of hematologic toxicity was more common than non-hematologic toxicity. Thrombocytopenia (67%) and nausea (67%) were the most common adverse event. No treatment related death was recorded. All patients discontinued therapy due to disease progression. Conclusions: In this single institution retrospective outcome analysis, FOLFIRINOX was shown to have activity in maintaining disease control as either a first or second line therapy in advanced cholangiocarcinoma. Hematologic and non-hematologic side effects were frequent but manageable without significant treatment delay or discontinuation. There was no treatment related deaths.","Source":"Google Scholar","category":"HUMAN","training_data":"Efficacy And Safety Of Folfirinox In Advanced Cholangiocarcinoma Background: Cholangiocarcinomas are invasive carcinomas of uncommon diagnosis and often diagnosed at an advanced and metastatic stage. To this date, there is limited clinical data to support a standard chemotherapy regimen. Single agent systemic chemotherapy such as 5FU or gemcitabine achieves ORR of about 25% while combination regimens including 5-FU, adriamycin, mitomycin or 5-FU and cisplatin has OS of less than a year. Methods: We conducted a single institution retrospective analysis of survival, response and toxicity in patients with advanced or metastatic hepatobiliary carcinoma who had been treated with fluoropyrimidine, irinotecan, and oxaliplatin combination therapy from October 2008 to May 2015. Primary endpoint was PFS measured as the date of first treatment until evidence of clinical progression and/or death. Secondary endpoint was toxicity based on National Cancer Institute Common Terminology Criteria for Adverse Events(NCI CTCAE) for non hematologic and hematologic toxicity. Patients were age greater or equal to 18, histologically confirmed, locally advanced unresectable or metastatic adenocarcinoma of the biliary tract (intrahepatic or extrahepatic cholangiocarcinoma), treatment naive or one prior chemotherapy, ECOG performance status of 0-2. Results: Twenty-five patients were eligible for analysis. A total of six patients (24%) received FOLFIRINOX either as first line therapy or as a second line therapy after progression on gemcitabine based regimen. The median PFS was 5 months (151 days). The median OS was about 14.5 months (436 days). Frequency of hematologic toxicity was more common than non-hematologic toxicity. Thrombocytopenia (67%) and nausea (67%) were the most common adverse event. No treatment related death was recorded. All patients discontinued therapy due to disease progression. Conclusions: In this single institution retrospective outcome analysis, FOLFIRINOX was shown to have activity in maintaining disease control as either a first or second line therapy in advanced cholangiocarcinoma. Hematologic and non-hematologic side effects were frequent but manageable without significant treatment delay or discontinuation. There was no treatment related deaths. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"predictive value tumor proliferative indices periampullary cancers ki 67 mitotic activity index mi volume corrected mitotic index m v using tissue microarrays background morphometry nuclear ki 67 labelling mitotic activity index mi volume corrected mitotic index m v forperiampullarycancersusingtissuemicroarrayshas performed previously purpose study assess indices tissue microarray tma sections constructed patients periampullary cancers study association clinicopathological variables methods immunohistochemical staining ki 67 performed formalin xed pancreatic tma sections expression ki 67 assessed percentage cancer cell nuclei expressing mib1 mi mean percentage ki 67 10 random high power elds m v calculated standardizing mi connective tissue volume microscope parameters tumor using established protocols results patients c70 years periampullary cancers higher ki 67 expression 15 compared patients 70 years age v2 3 9 p 0 047 ki 67 expression higher tumors c2 cm v2 4 9 p 0 028 compared smaller tumors higher mi 15 clearly associated worsening histological grade v2 9 2 p 0 010 median survival tumors pancreaticobiliary subtype pancreatic ductal adenocarcinoma cholangiocarcinoma 43 months group m v score 20 compared 18 months group score c20 p 0 001 statistically signi cant difference survival based m v score tumors intestinal subtype ampullary duodenal adenocarcinoma conclusions periampullary cancers ki 67 mi proliferative indices predictive tumor behavior m v predictive survival tumors pancreaticobiliary subtype google scholar","probabilities":0.9467213,"Title":"Predictive Value Of Tumor Proliferative Indices In Periampullary Cancers: Ki-67 Mitotic Activity Index (Mi) And Volume Corrected Mitotic Index (M/V) Using Tissue Microarrays","Abstract":"Background Morphometry [nuclear Ki-67 labelling, mitotic activity index (MI), and volume-corrected mitotic index (M/V)]forperiampullarycancersusingtissuemicroarrayshas not been performed previously. The purpose of the study was to assess these indices on tissue microarray (TMA) sections constructed from patients with periampullary cancers and study their association with clinicopathological variables. Methods Immunohistochemical staining for Ki-67 was performed on formalin-fixed pancreatic TMA sections. Expression of Ki-67 was assessed as the percentage of cancer cell nuclei expressing MIB1, MI as the mean percentage of Ki-67 from 10 random high-power fields, and M/V was calculated after standardizing MI for connective tissue volume and microscope parameters in the tumor using established protocols. Results Patients C70 years with periampullary cancers had higher Ki-67 expression ([15) compared with patients \\70 years of age (v2 = 3.9, P = 0.047). Ki-67 expression was higher in tumors C2 cm ( v2 = 4.9, P = 0.028)\ncompared with smaller tumors. Higher MI ([15) was clearly associated with worsening histological grade (v2 = 9.2, P = 0.010). The median survival for tumors of the pancreaticobiliary subtype (pancreatic ductal adenocarcinoma and cholangiocarcinoma) was 43 months in the group with an M/V score of \\20, compared with 18 months for the group with a score C20 (P = 0.001). There was no statistically significant difference in survival, based on M/V score, for tumors of the intestinal subtype (ampullary and duodenal adenocarcinoma). Conclusions In periampullary cancers, Ki-67 and MI are proliferative indices predictive of tumor behavior. M/V was predictive of survival in tumors of the pancreaticobiliary subtype","Source":"Google Scholar","category":"ANIMAL","training_data":"Predictive Value Of Tumor Proliferative Indices In Periampullary Cancers: Ki-67 Mitotic Activity Index (Mi) And Volume Corrected Mitotic Index (M/V) Using Tissue Microarrays Background Morphometry [nuclear Ki-67 labelling, mitotic activity index (MI), and volume-corrected mitotic index (M/V)]forperiampullarycancersusingtissuemicroarrayshas not been performed previously. The purpose of the study was to assess these indices on tissue microarray (TMA) sections constructed from patients with periampullary cancers and study their association with clinicopathological variables. Methods Immunohistochemical staining for Ki-67 was performed on formalin-fixed pancreatic TMA sections. Expression of Ki-67 was assessed as the percentage of cancer cell nuclei expressing MIB1, MI as the mean percentage of Ki-67 from 10 random high-power fields, and M/V was calculated after standardizing MI for connective tissue volume and microscope parameters in the tumor using established protocols. Results Patients C70 years with periampullary cancers had higher Ki-67 expression ([15) compared with patients \\70 years of age (v2 = 3.9, P = 0.047). Ki-67 expression was higher in tumors C2 cm ( v2 = 4.9, P = 0.028)\ncompared with smaller tumors. Higher MI ([15) was clearly associated with worsening histological grade (v2 = 9.2, P = 0.010). The median survival for tumors of the pancreaticobiliary subtype (pancreatic ductal adenocarcinoma and cholangiocarcinoma) was 43 months in the group with an M/V score of \\20, compared with 18 months for the group with a score C20 (P = 0.001). There was no statistically significant difference in survival, based on M/V score, for tumors of the intestinal subtype (ampullary and duodenal adenocarcinoma). Conclusions In periampullary cancers, Ki-67 and MI are proliferative indices predictive of tumor behavior. M/V was predictive of survival in tumors of the pancreaticobiliary subtype Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"postoperative radiotherapy dose correlates locoregional control patients extra hepatic bile duct cancer purpose evaluate results postoperative radiotherapy patients extra hepatic bile duct cancer ehbdc identify prognostic factors local control survival materials methods january 2001 december 2010 retrospectively reviewed cases 70 patients ehbdc undergone curative resection received postoperative radiotherapy median radiation dose 50 4 gy range 41 4 54 gy resection margin status r0 30 patients 42 9 r1 25 patients 35 7 r2 15 patients 21 4 results 5 year rates overall survival os event free survival efs locoregional control lrc patients 42 9 38 3 61 2 respectively major pattern failure distant relapses 33 patients 47 1 multivariate analysis showed postradiotherapy ca19 9 level radiation dose 50 gy r2 resection margins perineural invasion stage significant prognostic factors os efs lrc os significantly different patients receiving r0 r1 resections significantly lower among receiving r2 resection 54 6 56 1 7 1 r0 r1 r2 resections respectively conclusion patients ehbdc undergone curative resection postoperative radiotherapy dose less 50 gy suboptimal os lrc higher radiation doses may needed obtain better lrc investigation novel therapy palliative treatment considered patients receiving r2 resection stn","probabilities":0.9799733,"Title":"Postoperative Radiotherapy Dose Correlates With Locoregional Control In Patients With Extra-Hepatic Bile Duct Cancer","Abstract":"Purpose: To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival. \r\n\r\n Materials and methods: Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%). \r\n\r\n Results: The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (≥50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). \r\n\r\n Conclusion: In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection.","Source":"STN","category":"HUMAN","training_data":"Postoperative Radiotherapy Dose Correlates With Locoregional Control In Patients With Extra-Hepatic Bile Duct Cancer Purpose: To evaluate the results of postoperative radiotherapy in patients with extra-hepatic bile duct cancer (EHBDC) and identify the prognostic factors for local control and survival. \r\n\r\n Materials and methods: Between January 2001 and December 2010, we retrospectively reviewed the cases of 70 patients with EHBDC who had undergone curative resection and received postoperative radiotherapy. The median radiation dose was 50.4 Gy (range, 41.4 to 54 Gy). The resection margin status was R0 in 30 patients (42.9%), R1 in 25 patients (35.7%), and R2 in 15 patients (21.4%). \r\n\r\n Results: The 5-year rates of overall survival (OS), event-free survival (EFS), and locoregional control (LRC) for all patients were 42.9%, 38.3%, and 61.2%, respectively. The major pattern of failure was distant relapses (33 patients, 47.1%). A multivariate analysis showed that the postradiotherapy CA19-9 level, radiation dose (≥50 Gy), R2 resection margins, perineural invasion, and T stage were the significant prognostic factors for OS, EFS, and LRC. OS was not significantly different between the patients receiving R0 and R1 resections, but was significantly lower among those receiving R2 resection (54.6%, 56.1%, and 7.1% for R0, R1, and R2 resections, respectively). \r\n\r\n Conclusion: In patients with EHBDC who had undergone curative resection, a postoperative radiotherapy dose less than 50 Gy was suboptimal for OS and LRC. Higher radiation doses may be needed to obtain better LRC. Further investigation of novel therapy or palliative treatment should be considered for patients receiving R2 resection. STN","prediction_labels":"HUMAN"},{"cleaned":"bland embolization treatment intrahepatic cholangiocarcinoma analysis radiologic outcomes survival purpose unresectable cholangiocarcinoma limited treatment outcomes poor survival locoregional therapies shown limited outcomes although limited data exists bland embolization purpose study analyze radiologic response overall survival complications bland embolization patients unresectable intrahepatic cholangiocarcinoma icc materials methods single center retrospective study included 18 patients unresectable icc underwent total 25 bland embolization treatments 9 year period tumor response assessed modified response evaluation criteria solid tumors mrecist criteria follow computed tomography magnetic resonance imaging scans patients stratified tumor number morphology infiltrative vs peripheral tumor burden survival analyzed using kaplan meier technique compared using log rank test complications graded based sir guidelines results 14 patients received imaging followup 2 partial response 6 stable disease 6 progressive disease based mrecist median survival mean survival time embolization 7 7 95 confidence interval ci 6 7 8 7 months 12 2 95 ci 5 1 19 3 months respectively 6 12 months survival estimates 71 24 respectively one patient greater class b major complication severe pain requiring prolonged stay conclusion bland embolization cholangiocarcinoma resulted 57 rate partial radiologic response stable disease median 7 7 month overall survival results suggest bland embolization may reasonable treatment strategy consider given paucity effective therapies unresectable icc google scholar","probabilities":0.9799733,"Title":"Bland Embolization For Treatment Of Intrahepatic Cholangiocarcinoma: Analysis Of Radiologic Outcomes And Survival","Abstract":"Purpose\nUnresectable cholangiocarcinoma has limited treatment outcomes and poor survival. Locoregional therapies have shown limited outcomes although very limited data exists for bland embolization. The purpose of this study was to analyze radiologic response, overall survival, and complications of bland embolization for patients with unresectable intrahepatic cholangiocarcinoma (ICC).\nMaterials and Methods\nThis single-center retrospective study included 18 patients with unresectable ICC who underwent total of 25 bland embolization treatments over a 9 year period. Tumor response was assessed with the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria on follow-up computed tomography or magnetic resonance imaging scans. Patients were stratified by tumor number, morphology (infiltrative vs. peripheral), and tumor burden. Survival was analyzed using the Kaplan-Meier technique and compared using the log rank test. Complications were graded based SIR guidelines.\nResults\nOut of 14 patients who received imaging followup, 2 had a partial response, 6 had stable disease, and 6 had progressive disease based on mRECIST. Median survival and mean survival from the time of embolization was 7.7 (95% confidence interval (CI) 6.7-8.7) months and 12.2 (95% CI 5.1 - 19.3) months, respectively. The 6 and 12 months survival estimates were 71% and 24% respectively. Only one patient had a greater than Class B major complication of severe pain requiring prolonged stay.\nConclusion\nBland embolization for cholangiocarcinoma resulted in a 57% rate of partial radiologic response or stable disease with a median 7.7 month overall survival. These results suggest that bland embolization may be a reasonable treatment strategy to consider, given the paucity of effective therapies for unresectable ICC.","Source":"Google Scholar","category":"HUMAN","training_data":"Bland Embolization For Treatment Of Intrahepatic Cholangiocarcinoma: Analysis Of Radiologic Outcomes And Survival Purpose\nUnresectable cholangiocarcinoma has limited treatment outcomes and poor survival. Locoregional therapies have shown limited outcomes although very limited data exists for bland embolization. The purpose of this study was to analyze radiologic response, overall survival, and complications of bland embolization for patients with unresectable intrahepatic cholangiocarcinoma (ICC).\nMaterials and Methods\nThis single-center retrospective study included 18 patients with unresectable ICC who underwent total of 25 bland embolization treatments over a 9 year period. Tumor response was assessed with the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria on follow-up computed tomography or magnetic resonance imaging scans. Patients were stratified by tumor number, morphology (infiltrative vs. peripheral), and tumor burden. Survival was analyzed using the Kaplan-Meier technique and compared using the log rank test. Complications were graded based SIR guidelines.\nResults\nOut of 14 patients who received imaging followup, 2 had a partial response, 6 had stable disease, and 6 had progressive disease based on mRECIST. Median survival and mean survival from the time of embolization was 7.7 (95% confidence interval (CI) 6.7-8.7) months and 12.2 (95% CI 5.1 - 19.3) months, respectively. The 6 and 12 months survival estimates were 71% and 24% respectively. Only one patient had a greater than Class B major complication of severe pain requiring prolonged stay.\nConclusion\nBland embolization for cholangiocarcinoma resulted in a 57% rate of partial radiologic response or stable disease with a median 7.7 month overall survival. These results suggest that bland embolization may be a reasonable treatment strategy to consider, given the paucity of effective therapies for unresectable ICC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"elevated levels circulating osteopontin patients cholangiocarcinoma predict poor survival tumor resection abstract available google scholar","probabilities":0.9799733,"Title":"Elevated Levels Of Circulating Osteopontin In Patients With Cholangiocarcinoma Predict Poor Survival After Tumor Resection","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Elevated Levels Of Circulating Osteopontin In Patients With Cholangiocarcinoma Predict Poor Survival After Tumor Resection Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"circulating copper zinc levels risk hepatobiliary cancers europeans background copper zinc essential micronutrients cofactors many enzymatic reactions may involved liver cancer development aimed assess pre diagnostic circulating levels copper zinc ratio cu zn relation hepatocellular carcinoma hcc intrahepatic bile duct ihbd gall bladder biliary tract gbtc cancers methods nested case control study conducted within european prospective investigation cancer nutrition cohort serum zinc copper levels measured baseline blood samples total reflection x ray fluorescence cancer cases hcc n 106 ihdb n 34 gbtc n 96 matched controls 1 1 cu zn ratio indicator balance micronutrients computed multivariable adjusted odds ratios 95 confidence intervals 95 ci used estimate cancer risk results hcc highest vs lowest tertile showed strong inverse association zinc 0 36 95 ci 0 13 0 98 p trend 0 0123 association copper 1 06 95 ci 0 45 2 46 p trend 0 8878 multivariable models calculated cu zn ratio showed positive association hcc 4 63 95 ci 1 41 15 27 p trend 0 0135 ihbc gbtc significant associations observed conclusions zinc may role preventing liver cancer development finding requires investigation settings pubmed","probabilities":0.9799733,"Title":"Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans","Abstract":"BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers. METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk. RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, P(trend)=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, P(trend)=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, P(trend)=0.0135). For IHBC and GBTC, no significant associations were observed. CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings.","Source":"PubMed","category":"HUMAN","training_data":"Circulating copper and zinc levels and risk of hepatobiliary cancers in Europeans BACKGROUND: Copper and zinc are essential micronutrients and cofactors of many enzymatic reactions that may be involved in liver-cancer development. We aimed to assess pre-diagnostic circulating levels of copper, zinc and their ratio (Cu/Zn) in relation to hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBD) and gall bladder and biliary tract (GBTC) cancers. METHODS: A nested case-control study was conducted within the European Prospective Investigation into Cancer and Nutrition cohort. Serum zinc and copper levels were measured in baseline blood samples by total reflection X-ray fluorescence in cancer cases (HCC n=106, IHDB n=34, GBTC n=96) and their matched controls (1:1). The Cu/Zn ratio, an indicator of the balance between the micronutrients, was computed. Multivariable adjusted odds ratios and 95% confidence intervals (OR; 95% CI) were used to estimate cancer risk. RESULTS: For HCC, the highest vs lowest tertile showed a strong inverse association for zinc (OR=0.36; 95% CI: 0.13-0.98, P(trend)=0.0123), but no association for copper (OR=1.06; 95% CI: 0.45-2.46, P(trend)=0.8878) in multivariable models. The calculated Cu/Zn ratio showed a positive association for HCC (OR=4.63; 95% CI: 1.41-15.27, P(trend)=0.0135). For IHBC and GBTC, no significant associations were observed. CONCLUSIONS: Zinc may have a role in preventing liver-cancer development, but this finding requires further investigation in other settings. PubMed","prediction_labels":"HUMAN"},{"cleaned":"circulating mir 106a novel prognostic lymph node metastasis indicator cholangiocarcinoma cholangiocarcinoma cca common biliary malignancy despite continuing advances novel indicators urgently needed identify patients poor prognosis several micrornas mirnas reported dysregulated cca tissues purpose current study explore potential use certain mirnas serum indicators total 157 individuals including103 cca patients recruited study first used qrt pcr evaluate 5 cca related mirnas serum 95 individuals identify significantly deregulated mirnas logistic regression used analyse potential variables influencing lymph node metastasis cox proportional hazards regression models applied determine association possible prognostic variables overall survival os observed decreased serum mir 106a confers higher likelihood lymph node metastasis hazard ratio hr 18 3 95 confidence interval ci 5 9 56 4 p 0 01 additionally lower circulating mir 106a levels hr 5 1 95 ci 2 2 11 8 p 0 01 non radical surgery hr 4 2 95 ci 2 3 7 7 p 0 01 independent predictors poor prognosis together reduced expression serum mir 106a powerful prognostic indicator cca patients dismal outcome cca patients might correlate higher risk lymph node metastasis pubmed","probabilities":0.88235295,"Title":"Circulating miR-106a is a Novel Prognostic and Lymph Node Metastasis Indicator for Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a common biliary malignancy. Despite continuing advances, novel indicators are urgently needed to identify patients with a poor prognosis. Several microRNAs (miRNAs) have been reported to be dysregulated in CCA tissues. The purpose of the current study was to explore the potential use of certain miRNAs as serum indicators. A total of 157 individuals, including103 CCA patients, were recruited into this study. We first used qRT-PCR to evaluate 5 CCA-related miRNAs in the serum of 95 individuals to identify significantly deregulated miRNAs. A logistic regression was used to analyse the potential variables influencing lymph node metastasis. Cox proportional hazards regression models were applied to determine the association between possible prognostic variables and overall survival (OS). We observed that decreased serum miR-106a confers a higher likelihood of lymph node metastasis [hazard ratio (HR) 18.3, 95% confidence interval (CI) 5.9-56.4, p < 0.01]. Additionally, lower circulating miR-106a levels (HR 5.1; 95% CI 2.2-11.8; p < 0.01) and non-radical surgery (HR 4.2; 95% CI 2.3-7.7; p < 0.01) were independent predictors for poor prognosis. Together, reduced expression of serum miR-106a is a powerful prognostic indicator for CCA patients. The dismal outcome of these CCA patients might correlate with a higher risk of lymph node metastasis.","Source":"PubMed","category":"HUMAN","training_data":"Circulating miR-106a is a Novel Prognostic and Lymph Node Metastasis Indicator for Cholangiocarcinoma Cholangiocarcinoma (CCA) is a common biliary malignancy. Despite continuing advances, novel indicators are urgently needed to identify patients with a poor prognosis. Several microRNAs (miRNAs) have been reported to be dysregulated in CCA tissues. The purpose of the current study was to explore the potential use of certain miRNAs as serum indicators. A total of 157 individuals, including103 CCA patients, were recruited into this study. We first used qRT-PCR to evaluate 5 CCA-related miRNAs in the serum of 95 individuals to identify significantly deregulated miRNAs. A logistic regression was used to analyse the potential variables influencing lymph node metastasis. Cox proportional hazards regression models were applied to determine the association between possible prognostic variables and overall survival (OS). We observed that decreased serum miR-106a confers a higher likelihood of lymph node metastasis [hazard ratio (HR) 18.3, 95% confidence interval (CI) 5.9-56.4, p < 0.01]. Additionally, lower circulating miR-106a levels (HR 5.1; 95% CI 2.2-11.8; p < 0.01) and non-radical surgery (HR 4.2; 95% CI 2.3-7.7; p < 0.01) were independent predictors for poor prognosis. Together, reduced expression of serum miR-106a is a powerful prognostic indicator for CCA patients. The dismal outcome of these CCA patients might correlate with a higher risk of lymph node metastasis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"trends hospital variations surgical outcomes cholangiocarcinoma new york state background population based study examined surgical outcomes hospital post acute care resource use operations cholangiocarcinoma 2005 2012 study design using new york state hospital claims identified subjects intrahepatic tumor underwent hepatectomy n 2089 subjects perihilar tumor underwent hepatectomy biliary enteric anastomosis bea n 389 bea n 3721 subjects distal cholangiocarcinoma undergoing pancreatectomy pancreaticoduodenectomy n 228 performed trend analyses group calculated overall risk adjusted mortality complication 30 day readmission rates hospitals using multivariable logistic regressions results mortality rate roughly 12 years perihilar cases undergoing hepatectomy bea significantly higher rates 3 groups p 0 000 overall complication rate 40 subjects undergoing hepatectomy bea doubling rate subjects undergoing hepatectomy bea alone p 0 000 average los declined markedly perihilar cases undergoing hepatectomy bea 21 days 2005 16 days 2012 subjects distal cholangiocarcinoma 22 days 2005 16 days 2012 outcomes change dramatically risk adjusted hospital outcome rates varied substantially conclusions surgical patients cholangiocarcinoma incur considerable mortality postoperative complications resource uses especially among undergoing hepatectomy bea perihilar tumors stn","probabilities":0.9799733,"Title":"Trends And Hospital Variations In Surgical Outcomes For Cholangiocarcinoma In New York State","Abstract":"Background: This population-based study examined surgical outcomes and hospital and post-acute care resource use after operations of cholangiocarcinoma during 2005-2012. \r\n\r\n Study design: Using New York State hospital claims, we identified subjects with intrahepatic tumor who underwent hepatectomy only (n = 2089), subjects with perihilar tumor who underwent hepatectomy and biliary-enteric anastomosis (BEA; n = 389) or BEA only (n = 3721), and subjects with distal cholangiocarcinoma undergoing pancreatectomy or pancreaticoduodenectomy (n = 228). We performed trend analyses for each group and calculated overall risk-adjusted mortality, complication, and 30-day readmission rates for hospitals using multivariable logistic regressions. \r\n\r\n Results: Mortality rate was roughly 12 % over years for perihilar cases undergoing hepatectomy and BEA, significantly higher than the rates of other 3 groups (p = 0.000). The overall complication rate was 40 % for subjects undergoing both hepatectomy and BEA, more than doubling the rate for subjects undergoing hepatectomy or BEA alone (p = 0.000). Average LOS declined markedly for perihilar cases undergoing hepatectomy and BEA (from 21 days in 2005 to 16 days in 2012) and subjects with distal cholangiocarcinoma (from 22 days in 2005 to 16 days in 2012), but other outcomes did not change dramatically. Risk-adjusted hospital outcome rates varied substantially. \r\n\r\n Conclusions: Surgical patients with cholangiocarcinoma incur considerable mortality, postoperative complications, and resource uses, especially among those undergoing hepatectomy and BEA for perihilar tumors.","Source":"STN","category":"HUMAN","training_data":"Trends And Hospital Variations In Surgical Outcomes For Cholangiocarcinoma In New York State Background: This population-based study examined surgical outcomes and hospital and post-acute care resource use after operations of cholangiocarcinoma during 2005-2012. \r\n\r\n Study design: Using New York State hospital claims, we identified subjects with intrahepatic tumor who underwent hepatectomy only (n = 2089), subjects with perihilar tumor who underwent hepatectomy and biliary-enteric anastomosis (BEA; n = 389) or BEA only (n = 3721), and subjects with distal cholangiocarcinoma undergoing pancreatectomy or pancreaticoduodenectomy (n = 228). We performed trend analyses for each group and calculated overall risk-adjusted mortality, complication, and 30-day readmission rates for hospitals using multivariable logistic regressions. \r\n\r\n Results: Mortality rate was roughly 12 % over years for perihilar cases undergoing hepatectomy and BEA, significantly higher than the rates of other 3 groups (p = 0.000). The overall complication rate was 40 % for subjects undergoing both hepatectomy and BEA, more than doubling the rate for subjects undergoing hepatectomy or BEA alone (p = 0.000). Average LOS declined markedly for perihilar cases undergoing hepatectomy and BEA (from 21 days in 2005 to 16 days in 2012) and subjects with distal cholangiocarcinoma (from 22 days in 2005 to 16 days in 2012), but other outcomes did not change dramatically. Risk-adjusted hospital outcome rates varied substantially. \r\n\r\n Conclusions: Surgical patients with cholangiocarcinoma incur considerable mortality, postoperative complications, and resource uses, especially among those undergoing hepatectomy and BEA for perihilar tumors. STN","prediction_labels":"HUMAN"},{"cleaned":"functional microrna library screen reveals mir 410 novel anti apoptotic regulator cholangiocarcinoma background cholangiocarcinoma characterized late diagnosis poor survival rate micrornas involved pathogenesis different cancer types including cholangiocarcinoma aim identify novel micrornas regulating cholangiocarcinoma cell growth vitro vivo methods functional microrna library screen performed human cholangiocarcinoma cells identify micrornas regulate cholangiocarcinoma cell growth real time pcr analysis evaluated mir 9 xiap mrna levels cholangiocarcinoma cells tumors results screen identified 21 micrornas regulated 50 cholangiocarcinoma cell growth mir 410 identified top suppressor growth overexpression significantly inhibited invasion colony formation ability cholangiocarcinoma cells bioinformatics analysis revealed microrna 410 exerts effects direct regulation x linked inhibitor apoptosis protein xiap furthermore overexpression mir 410 significantly reduced cholangiocarcinoma tumor growth xenograft mouse model induction apoptosis addition identified inverse relationship mir 410 xiap mrna levels human cholangiocarcinomas conclusions taken together study revealed novel microrna signaling pathway involved cholangiocarcinoma suggests manipulation mir 410 xiap pathway therapeutic potential cholangiocarcinoma stn","probabilities":0.9467213,"Title":"A Functional Microrna Library Screen Reveals Mir-410 As A Novel Anti-Apoptotic Regulator Of Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. \r\n\r\n Methods: A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. \r\n\r\n Results: The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. \r\n\r\n Conclusions: Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"A Functional Microrna Library Screen Reveals Mir-410 As A Novel Anti-Apoptotic Regulator Of Cholangiocarcinoma Background: Cholangiocarcinoma is characterized by late diagnosis and a poor survival rate. MicroRNAs have been involved in the pathogenesis of different cancer types, including cholangiocarcinoma. Our aim was to identify novel microRNAs regulating cholangiocarcinoma cell growth in vitro and in vivo. \r\n\r\n Methods: A functional microRNA library screen was performed in human cholangiocarcinoma cells to identify microRNAs that regulate cholangiocarcinoma cell growth. Real-time PCR analysis evaluated miR-9 and XIAP mRNA levels in cholangiocarcinoma cells and tumors. \r\n\r\n Results: The screen identified 21 microRNAs that regulated >50 % cholangiocarcinoma cell growth. MiR-410 was identified as the top suppressor of growth, while its overexpression significantly inhibited the invasion and colony formation ability of cholangiocarcinoma cells. Bioinformatics analysis revealed that microRNA-410 exerts its effects through the direct regulation of the X-linked inhibitor of apoptosis protein (XIAP). Furthermore, overexpression of miR-410 significantly reduced cholangiocarcinoma tumor growth in a xenograft mouse model through induction of apoptosis. In addition, we identified an inverse relationship between miR-410 and XIAP mRNA levels in human cholangiocarcinomas. \r\n\r\n Conclusions: Taken together, our study revealed a novel microRNA signaling pathway involved in cholangiocarcinoma and suggests that manipulation of the miR-410/XIAP pathway could have a therapeutic potential for cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"nutritional factors nutritional aspects biliary disorders bile acid lipid metabolism gallstone diseases pancreaticobiliary maljunction nutritional factors play key role pathogenesis biliary diseases gallstones pancreaticobiliary maljunction gallstones primarily classified cholesterol stone pigment stone according major composition cholesterol gallstone formation likely based upon supersaturated bile formation pigment stones formed bile rich bilirubin thus defects hepatic metabolism lipids organic anions lead biliary stones recent understanding cholesterol gallstone pathogenesis elaborated hand another important link biliary lipid degradation serious biliary disease namely pancreaticobiliary maljunction lysophosphatidylcholine lysopc derivative phosphatidylcholine hydrolysis phospholipase a2 highly abundant bioactive lipid mediator present circulation well bile increases bile lysopc phospholipase a2 reported pancreaticobiliary maljunction considered major risk factor biliary tract cancers oxidized fatty acids established potent ligand g2a member g protein coupled receptor family mediates diverse array biological processes including cell growth apoptosis thus lysopc free fatty acids supposed play important role g2a biliary inflammation carcinogenesis pancreaticobiliary maljunction taken together nutritional factors especially lipid compounds seemingly crucial pathogenesis biliary diseases causal relationship reviewed mainly authors previous publications pubmed","probabilities":0.962963,"Title":"Nutritional factors (nutritional aspects) in biliary disorders: bile acid and lipid metabolism in gallstone diseases and pancreaticobiliary maljunction","Abstract":"Nutritional factors play a key role in the pathogenesis of biliary diseases such as gallstones and pancreaticobiliary maljunction. Gallstones are primarily classified into cholesterol stone and pigment stone according to the major composition. Cholesterol gallstone formation is very likely based upon supersaturated bile formation, and pigment stones are formed in bile rich in bilirubin. Thus, defects of hepatic metabolism of lipids and organic anions lead to biliary stones. Here, the recent understanding of cholesterol gallstone pathogenesis is elaborated. On the other hand, there is another important link of biliary lipid degradation to serious biliary disease, namely pancreaticobiliary maljunction. Lysophosphatidylcholine (lysoPC), a derivative of phosphatidylcholine hydrolysis by phospholipase A2, is a highly abundant bioactive lipid mediator present in circulation as well as in bile. Increases in bile of lysoPC and phospholipase A2 have been reported in pancreaticobiliary maljunction and considered to be the major risk factor for biliary tract cancers. Further, oxidized fatty acids have been established as a potent ligand for G2A, a member of G protein-coupled receptor family that mediates a diverse array of biological processes including cell growth and apoptosis. Thus, both of lysoPC and free fatty acids are supposed to play an important role through G2A in biliary inflammation and carcinogenesis of pancreaticobiliary maljunction. Taken together, nutritional factors, especially lipid compounds, are seemingly crucial in the pathogenesis of biliary diseases, and such a causal relationship is reviewed by mainly authors' previous publications.","Source":"PubMed","category":"HUMAN","training_data":"Nutritional factors (nutritional aspects) in biliary disorders: bile acid and lipid metabolism in gallstone diseases and pancreaticobiliary maljunction Nutritional factors play a key role in the pathogenesis of biliary diseases such as gallstones and pancreaticobiliary maljunction. Gallstones are primarily classified into cholesterol stone and pigment stone according to the major composition. Cholesterol gallstone formation is very likely based upon supersaturated bile formation, and pigment stones are formed in bile rich in bilirubin. Thus, defects of hepatic metabolism of lipids and organic anions lead to biliary stones. Here, the recent understanding of cholesterol gallstone pathogenesis is elaborated. On the other hand, there is another important link of biliary lipid degradation to serious biliary disease, namely pancreaticobiliary maljunction. Lysophosphatidylcholine (lysoPC), a derivative of phosphatidylcholine hydrolysis by phospholipase A2, is a highly abundant bioactive lipid mediator present in circulation as well as in bile. Increases in bile of lysoPC and phospholipase A2 have been reported in pancreaticobiliary maljunction and considered to be the major risk factor for biliary tract cancers. Further, oxidized fatty acids have been established as a potent ligand for G2A, a member of G protein-coupled receptor family that mediates a diverse array of biological processes including cell growth and apoptosis. Thus, both of lysoPC and free fatty acids are supposed to play an important role through G2A in biliary inflammation and carcinogenesis of pancreaticobiliary maljunction. Taken together, nutritional factors, especially lipid compounds, are seemingly crucial in the pathogenesis of biliary diseases, and such a causal relationship is reviewed by mainly authors' previous publications. PubMed","prediction_labels":"HUMAN"},{"cleaned":"type ii diabetes mellitus associated reduced risk cholangiocarcinoma patients biliary tract diseases yet reported whether type ii diabetes mellitus dm associated increased cholangiocarcinoma cc risk patients biliary tract diseases identified 123 050 patients concomitantly diagnosed biliary tract diseases dm 1998 2010 control cohort consisted 122 721 individuals biliary tract diseases dm cohorts followed end 2010 estimate risk cc also compared risk cc dm non dm cohorts without biliary tract diseases overall incidence cc 21 lower among dm patients among control patients 1 11 vs 1 41 per 1 000 person years dm cohorts exhibited significantly reduced risks intrahepatic extrahepatic cc multivariable cox proportional hazards regression model used adjusted hazard ratio hr cc 0 74 95 confidence interval ci 0 66 0 82 dm cohort comparison control cohort age specific data indicated compared control patients adjusted hrs dm patients significantly lower among patients 50 64 adjusted hr 0 67 95 ci 0 55 0 82 65 74 years old adjusted hr 0 70 95 ci 0 59 0 84 furthermore dm associated lower risk cc among patients biliary diseases regardless presence comorbidities status cholecystectomy patients without biliary tract diseases dm associated significantly increased risk cc adjusted hr 1 58 95 ci 1 37 1 82 pubmed","probabilities":0.9799733,"Title":"Type II diabetes mellitus is associated with a reduced risk of cholangiocarcinoma in patients with biliary tract diseases","Abstract":"It has not yet been reported whether Type II diabetes mellitus (DM) is associated with an increased cholangiocarcinoma (CC) risk in patients with biliary tract diseases. We identified 123,050 patients concomitantly diagnosed with biliary tract diseases and DM between 1998 and 2010. The control cohort consisted of 122,721 individuals with biliary tract diseases but not DM. Both cohorts were followed-up until the end of 2010 to estimate the risk of CC. We also compared the risk of CC between DM and non-DM cohorts without biliary tract diseases. Overall, the incidence of CC was 21% lower among the DM patients than among the control patients (1.11 vs. 1.41 per 1,000 person-years). DM cohorts exhibited significantly reduced risks for both intrahepatic and extrahepatic CC. A multivariable Cox proportional hazards regression model was used, and the adjusted hazard ratio (HR) of CC was 0.74 (95% confidence interval [CI], 0.66-0.82) for the DM cohort in comparison with the control cohort. The age-specific data indicated that compared with the control patients, the adjusted HRs for the DM patients were significantly lower among patients 50-64 (adjusted HR = 0.67; 95% CI = 0.55-0.82) and 65-74 years old (adjusted HR = 0.70; 95% CI, 0.59-0.84). Furthermore, DM was associated with a lower risk of CC among patients with biliary diseases, regardless of the presence of comorbidities and the status of cholecystectomy. In the patients without biliary tract diseases, DM is associated with significantly increased risk of CC (adjusted HR = 1.58; 95% CI, 1.37-1.82).","Source":"PubMed","category":"HUMAN","training_data":"Type II diabetes mellitus is associated with a reduced risk of cholangiocarcinoma in patients with biliary tract diseases It has not yet been reported whether Type II diabetes mellitus (DM) is associated with an increased cholangiocarcinoma (CC) risk in patients with biliary tract diseases. We identified 123,050 patients concomitantly diagnosed with biliary tract diseases and DM between 1998 and 2010. The control cohort consisted of 122,721 individuals with biliary tract diseases but not DM. Both cohorts were followed-up until the end of 2010 to estimate the risk of CC. We also compared the risk of CC between DM and non-DM cohorts without biliary tract diseases. Overall, the incidence of CC was 21% lower among the DM patients than among the control patients (1.11 vs. 1.41 per 1,000 person-years). DM cohorts exhibited significantly reduced risks for both intrahepatic and extrahepatic CC. A multivariable Cox proportional hazards regression model was used, and the adjusted hazard ratio (HR) of CC was 0.74 (95% confidence interval [CI], 0.66-0.82) for the DM cohort in comparison with the control cohort. The age-specific data indicated that compared with the control patients, the adjusted HRs for the DM patients were significantly lower among patients 50-64 (adjusted HR = 0.67; 95% CI = 0.55-0.82) and 65-74 years old (adjusted HR = 0.70; 95% CI, 0.59-0.84). Furthermore, DM was associated with a lower risk of CC among patients with biliary diseases, regardless of the presence of comorbidities and the status of cholecystectomy. In the patients without biliary tract diseases, DM is associated with significantly increased risk of CC (adjusted HR = 1.58; 95% CI, 1.37-1.82). PubMed","prediction_labels":"HUMAN"},{"cleaned":"dihydroartemisinin inhibits tctp dependent metastasis gallbladder cancer background patients metastatic relapsed gallbladder cancer generally poor prognosis therefore targeting metastasis one arm therapeutic strategies treat gallbladder cancer methods levels translationally controlled tumor protein tctp measured samples gallbladder cancer immunohistochemical staining wound healing migration invasion assays used investigate motility cells western blot assay used investigate levels tctp proteins liver metastasis models lung metastasis models established investigate inhibitory effect dihydroartemisinin gallbladder cancer metastasis results tctp aberrantly expressed gallbladder cancer patients associated metastasis poor prognosis depleting tctp significantly inhibited gallbladder cancer cell migration invasion found dihydroartemisinin potent inhibitor tctp inhibited tctp dependent cell migration invasion reducing cell division control protein 42 homolog cdc42 activation addition mice xenografted tumors treatment dihydroartemisinin decreased gallbladder cancer cell metastases improved survival conclusions findings provide new insights therapeutic activity dihydroartemisinin treatment gallbladder cancer metastasis google scholar","probabilities":0.9467213,"Title":"Dihydroartemisinin Inhibits Tctp-Dependent Metastasis In Gallbladder Cancer","Abstract":"Background\nPatients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer.\nMethods\nLevels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins. Liver metastasis models and lung metastasis models were established to investigate the inhibitory effect of Dihydroartemisinin on gallbladder cancer metastasis.\nResults\nTCTP is aberrantly expressed in gallbladder cancer patients and associated with metastasis and a poor prognosis. Depleting TCTP significantly inhibited gallbladder cancer cell migration and invasion. We found that Dihydroartemisinin as a potent inhibitor of TCTP inhibited TCTP-dependent cell migration and invasion by reducing cell division control protein 42 homolog (Cdc42) activation. In addition, in mice with xenografted tumors, treatment with Dihydroartemisinin decreased gallbladder cancer cell metastases and improved survival.\nConclusions\nThese findings provide new insights into the therapeutic activity of Dihydroartemisinin as a treatment for gallbladder cancer metastasis.","Source":"Google Scholar","category":"ANIMAL","training_data":"Dihydroartemisinin Inhibits Tctp-Dependent Metastasis In Gallbladder Cancer Background\nPatients with metastatic or relapsed gallbladder cancer generally have a poor prognosis. Therefore, targeting metastasis is one arm of therapeutic strategies to treat gallbladder cancer.\nMethods\nLevels of translationally controlled tumor protein (TCTP) were measured in samples of gallbladder cancer by immunohistochemical staining. Wound healing, migration and invasion assays were used to investigate the motility of cells. Western blot assay was used to investigate the levels of TCTP and other proteins. Liver metastasis models and lung metastasis models were established to investigate the inhibitory effect of Dihydroartemisinin on gallbladder cancer metastasis.\nResults\nTCTP is aberrantly expressed in gallbladder cancer patients and associated with metastasis and a poor prognosis. Depleting TCTP significantly inhibited gallbladder cancer cell migration and invasion. We found that Dihydroartemisinin as a potent inhibitor of TCTP inhibited TCTP-dependent cell migration and invasion by reducing cell division control protein 42 homolog (Cdc42) activation. In addition, in mice with xenografted tumors, treatment with Dihydroartemisinin decreased gallbladder cancer cell metastases and improved survival.\nConclusions\nThese findings provide new insights into the therapeutic activity of Dihydroartemisinin as a treatment for gallbladder cancer metastasis. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"clinicopathologic significance minichromosome maintenance protein 2 tat interacting protein 30 expression benign malignant lesions gallbladder gallbladder cancers aggressive tumors poor prognosis high mortality rate find specific biological markers early diagnosis prognosis develop possible alternative treatment strategies examined minichromosome maintenance protein 2 mcm2 tat interacting protein 30 tip30 expression 108 gallbladder adenocarcinomas 15 gallbladder polyps 35 chronic cholecystitis tissues 46 peritumoral tissues using immunohistochemistry expression mcm2 significantly higher adenocarcinomas peritumoral tissues 8 41 p 01 adenomatous polyps 6 81 p 01 chronic cholecystitis 21 00 p 01 contrast tat interacting protein 30 expression significantly less adenocarcinomas peritumoral tissues 13 26 p 01 adenomatous polyps 4 76 p 05 chronic cholecystitis 18 93 p 01 benign lesions gallbladder epithelium positive mcm2 negative tat interacting protein 30 expression showed moderate severe atypical hyperplasia expression mcm2 absence tat interacting protein 30 significantly associated poor differentiation large tumor mass lymph node metastasis invasion adenocarcinoma univariate kaplan meier analysis showed either elevated mcm2 p 006 lowered tat interacting protein 30 p 006 expression closely associated shorter overall survival multivariate cox regression analysis revealed expression mcm2 p 007 nonexpression tat interacting protein 30 p 009 independent predictor poor prognosis adenocarcinoma results suggest overexpression mcm2 loss expression tat interacting protein 30 closely related carcinogenesis progression biological behavior prognosis gallbladder adenocarcinoma stn","probabilities":0.88235295,"Title":"Clinicopathologic Significance Of Minichromosome Maintenance Protein 2 And Tat-Interacting Protein 30 Expression In Benign And Malignant Lesions Of The Gallbladder","Abstract":"Gallbladder cancers are aggressive tumors with a poor prognosis and high mortality rate. To find specific biological markers for early diagnosis and prognosis and to develop possible alternative treatment strategies, we examined minichromosome maintenance protein 2 (MCM2) and Tat-interacting protein 30 (TIP30) expression in 108 gallbladder adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using immunohistochemistry. Expression of MCM2 was significantly higher in adenocarcinomas than in peritumoral tissues (χ² = 8.41; P < .01), adenomatous polyps (χ² = 6.81; P < .01), and chronic cholecystitis (χ² = 21.00; P < .01). In contrast, Tat-interacting protein 30 expression was significantly less in adenocarcinomas than in peritumoral tissues (χ² = 13.26; P < .01), adenomatous polyps (χ² = 4.76; P < .05), and chronic cholecystitis (χ² = 18.93; P < .01). The benign lesions in gallbladder epithelium with positive MCM2 or negative Tat-interacting protein 30 expression showed moderate to severe atypical hyperplasia. Expression of MCM2 and absence of Tat-interacting protein 30 were significantly associated with poor differentiation, large tumor mass, lymph node metastasis, and invasion of adenocarcinoma. Univariate Kaplan-Meier analysis showed that either elevated MCM2 (P = .006) or lowered Tat-interacting protein 30 (P = .006) expression was closely associated with shorter overall survival. Multivariate Cox regression analysis revealed that expression of MCM2 (P = .007) or nonexpression of Tat-interacting protein 30 (P = .009) was an independent predictor of a poor prognosis in adenocarcinoma. Our results suggest that overexpression of MCM2 or loss of expression of Tat-interacting protein 30 is closely related to carcinogenesis, progression, biological behavior, and prognosis of gallbladder adenocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Clinicopathologic Significance Of Minichromosome Maintenance Protein 2 And Tat-Interacting Protein 30 Expression In Benign And Malignant Lesions Of The Gallbladder Gallbladder cancers are aggressive tumors with a poor prognosis and high mortality rate. To find specific biological markers for early diagnosis and prognosis and to develop possible alternative treatment strategies, we examined minichromosome maintenance protein 2 (MCM2) and Tat-interacting protein 30 (TIP30) expression in 108 gallbladder adenocarcinomas, 15 gallbladder polyps, 35 chronic cholecystitis tissues, and 46 peritumoral tissues using immunohistochemistry. Expression of MCM2 was significantly higher in adenocarcinomas than in peritumoral tissues (χ² = 8.41; P < .01), adenomatous polyps (χ² = 6.81; P < .01), and chronic cholecystitis (χ² = 21.00; P < .01). In contrast, Tat-interacting protein 30 expression was significantly less in adenocarcinomas than in peritumoral tissues (χ² = 13.26; P < .01), adenomatous polyps (χ² = 4.76; P < .05), and chronic cholecystitis (χ² = 18.93; P < .01). The benign lesions in gallbladder epithelium with positive MCM2 or negative Tat-interacting protein 30 expression showed moderate to severe atypical hyperplasia. Expression of MCM2 and absence of Tat-interacting protein 30 were significantly associated with poor differentiation, large tumor mass, lymph node metastasis, and invasion of adenocarcinoma. Univariate Kaplan-Meier analysis showed that either elevated MCM2 (P = .006) or lowered Tat-interacting protein 30 (P = .006) expression was closely associated with shorter overall survival. Multivariate Cox regression analysis revealed that expression of MCM2 (P = .007) or nonexpression of Tat-interacting protein 30 (P = .009) was an independent predictor of a poor prognosis in adenocarcinoma. Our results suggest that overexpression of MCM2 or loss of expression of Tat-interacting protein 30 is closely related to carcinogenesis, progression, biological behavior, and prognosis of gallbladder adenocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"multicentre study impact factors may affect long term survival following pancreaticoduodenectomy distal cholangiocarcinoma background although peri operative mortality following pancreaticoduodenectomy pd distal cholangiocarcinoma dcc decreased post operative morbidity remains high aim study evaluate impact factors may affect long term survival patients dcc following pd methods patients underwent pd dcc january 2000 december 2015 5 tertiary referral centers underwent retrospective medical record review factors likely influence overall os disease free dfs survivals assessed univariate multivariate analysis results total 201 217 patients underwent pd dcc included analysis median os 39 months actuarial survival rates 1 3 5 years 85 53 39 recurrence occurred 123 61 patients median dfs 16 months actuarial survival rates 1 3 5 years 60 37 28 following multivariate analysis peri operative blood transfusions pbt associated worse os hr 2 25 1 31 3 85 p 0 003 dfs hr 2 08 1 24 3 5 p 0 005 conclusion study confirms negative impact pbt oncologic result following pd dcc pubmed","probabilities":0.9799733,"Title":"Multicentre study of the impact of factors that may affect long-term survival following pancreaticoduodenectomy for distal cholangiocarcinoma","Abstract":"BACKGROUND: Although the peri-operative mortality following pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) has decreased, the post-operative morbidity remains high. The aim of this study was to evaluate the impact of factors that may affect the long term survival for patients with DCC following PD. METHODS: All patients who underwent PD for DCC between January 2000 and December 2015 in 5 tertiary referral centers underwent retrospective medical record review. Factors likely to influence overall (OS) and disease-free (DFS) survivals were assessed by univariate and multivariate analysis. RESULTS: A total of 201 on 217 patients who underwent PD for DCC were included for further analysis. The median OS was 39 months, with actuarial survival rates at 1, 3, and 5 years of 85%, 53% and 39%. Recurrence occurred in 123 (61%) patients. The median DFS was 16 months, with actuarial survival rates at 1, 3 and 5 years of 60%, 37% and 28%. Following multivariate analysis, peri-operative blood transfusions (PBT) were associated to worse OS (HR = 2.25 [1.31-3.85], P = 0.003) and DFS (HR = 2.08 [1.24-3.5], P = 0.005). CONCLUSION: This study confirms the negative impact of PBT on the oncologic result following PD for DCC.","Source":"PubMed","category":"HUMAN","training_data":"Multicentre study of the impact of factors that may affect long-term survival following pancreaticoduodenectomy for distal cholangiocarcinoma BACKGROUND: Although the peri-operative mortality following pancreaticoduodenectomy (PD) for distal cholangiocarcinoma (DCC) has decreased, the post-operative morbidity remains high. The aim of this study was to evaluate the impact of factors that may affect the long term survival for patients with DCC following PD. METHODS: All patients who underwent PD for DCC between January 2000 and December 2015 in 5 tertiary referral centers underwent retrospective medical record review. Factors likely to influence overall (OS) and disease-free (DFS) survivals were assessed by univariate and multivariate analysis. RESULTS: A total of 201 on 217 patients who underwent PD for DCC were included for further analysis. The median OS was 39 months, with actuarial survival rates at 1, 3, and 5 years of 85%, 53% and 39%. Recurrence occurred in 123 (61%) patients. The median DFS was 16 months, with actuarial survival rates at 1, 3 and 5 years of 60%, 37% and 28%. Following multivariate analysis, peri-operative blood transfusions (PBT) were associated to worse OS (HR = 2.25 [1.31-3.85], P = 0.003) and DFS (HR = 2.08 [1.24-3.5], P = 0.005). CONCLUSION: This study confirms the negative impact of PBT on the oncologic result following PD for DCC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison thymidine phosphorylase expression prognostic factors gallbladder bile duct cancer background biliary tract cancers limitations information different location related pathogenesis clinico pathological characteristics goal study investigate anatomical site related similarities differences biliary tract cancers assess expression clinical significance functional proteins p53 cyclin d1 survivin thymidine phosphorylase ercc1 methods one hundred sixty one patients biliary tract adenocarcinomas underwent curative palliative surgery single institution october 1994 december 2003 evaluated retrospectively level protein expression p53 cyclin d1 survivin thymidine phosphorylase ercc1 assessed immunohistochemistry results respect clinico pathological characteristics gallbladder cancer frequent women bile duct cancer common men perineural invasion common bile duct cancer recurrence distant metastasis common gallbladder cancer immunohistochemical analysis revealed thymidine phosphorylase expression significantly higher gallbladder cancer bile duct cancer positive thymidine phosphorylase p53 staining associated advanced stage differentiation vascular invasion perineural invasion lymphatic invasion lymph node metastasis tnm stage independently predicted poor prognosis biliary tract cancer correlations seen clearly gallbladder cancer immunohistochemical staining patterns p53 cyclin d1 survivin thymidine phosphorylase ercc1 showed prognostic significance biliary tract cancers conclusions concluded gallbladder bile duct cancers considered separate diseases different clinico pathological characteristics prognostic factors addition hypothesize high expression thymidine phosphorylase gallbladder cancer results higher response rate capecitabine gallbladder cancer bile duct cancer stn","probabilities":0.9799733,"Title":"Comparison Of Thymidine Phosphorylase Expression And Prognostic Factors In Gallbladder And Bile Duct Cancer","Abstract":"Background: Biliary tract cancers have limitations in information about different location-related pathogenesis and clinico-pathological characteristics. The goal of this study was to investigate anatomical site-related similarities and differences in biliary tract cancers and to assess the expression and clinical significance of functional proteins such as p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1. \r\n\r\n Methods: One hundred and sixty-one patients with biliary tract adenocarcinomas, who underwent curative or palliative surgery in a single institution between October 1994 and December 2003 were evaluated, retrospectively. The level of protein expression of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 was assessed by immunohistochemistry. \r\n\r\n Results: With respect to clinico-pathological characteristics, gallbladder cancer was more frequent in women, and bile duct cancer was more common in men. Perineural invasion was more common in bile duct cancer. Recurrence as a distant metastasis was more common in gallbladder cancer. Immunohistochemical analysis revealed that thymidine phosphorylase expression was significantly higher in gallbladder cancer than in bile duct cancer. Positive thymidine phosphorylase and p53 staining were associated with an advanced stage. Differentiation, vascular invasion, perineural invasion, lymphatic invasion, lymph node metastasis, and TNM stage independently predicted poor prognosis in biliary tract cancer. These correlations were seen more clearly in gallbladder cancer. The immunohistochemical staining patterns of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 showed no prognostic significance in biliary tract cancers. \r\n\r\n Conclusions: We concluded that gallbladder and bile duct cancers are considered to be separate diseases with different clinico-pathological characteristics and prognostic factors. In addition, we hypothesize that high expression of thymidine phosphorylase by gallbladder cancer results in a higher response rate to capecitabine by gallbladder cancer than bile duct cancer.","Source":"STN","category":"HUMAN","training_data":"Comparison Of Thymidine Phosphorylase Expression And Prognostic Factors In Gallbladder And Bile Duct Cancer Background: Biliary tract cancers have limitations in information about different location-related pathogenesis and clinico-pathological characteristics. The goal of this study was to investigate anatomical site-related similarities and differences in biliary tract cancers and to assess the expression and clinical significance of functional proteins such as p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1. \r\n\r\n Methods: One hundred and sixty-one patients with biliary tract adenocarcinomas, who underwent curative or palliative surgery in a single institution between October 1994 and December 2003 were evaluated, retrospectively. The level of protein expression of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 was assessed by immunohistochemistry. \r\n\r\n Results: With respect to clinico-pathological characteristics, gallbladder cancer was more frequent in women, and bile duct cancer was more common in men. Perineural invasion was more common in bile duct cancer. Recurrence as a distant metastasis was more common in gallbladder cancer. Immunohistochemical analysis revealed that thymidine phosphorylase expression was significantly higher in gallbladder cancer than in bile duct cancer. Positive thymidine phosphorylase and p53 staining were associated with an advanced stage. Differentiation, vascular invasion, perineural invasion, lymphatic invasion, lymph node metastasis, and TNM stage independently predicted poor prognosis in biliary tract cancer. These correlations were seen more clearly in gallbladder cancer. The immunohistochemical staining patterns of p53, cyclin D1, survivin, thymidine phosphorylase, and ERCC1 showed no prognostic significance in biliary tract cancers. \r\n\r\n Conclusions: We concluded that gallbladder and bile duct cancers are considered to be separate diseases with different clinico-pathological characteristics and prognostic factors. In addition, we hypothesize that high expression of thymidine phosphorylase by gallbladder cancer results in a higher response rate to capecitabine by gallbladder cancer than bile duct cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"endoscopic biliary radiofrequency ablation prolong survival patients unrespectable extrahepatic cholangiocarcinoma background endoscopic placement biliary stents relieve jaundice main palliative treatment unresectable extrahepatic cholangiocarcinoma endoscopic biliary radiofrequency ablation rfa reported prolong stent patency may beneficial improving patient survival however available evidence still insufficient reported studies retrospective case series aim study explore clinical effect safety rfa patients unresectable extrahepatic cholangiocarcinoma methods 65 patients unresectable extrahepatic cholangiocarcinoma except bismuth type iii iv hilar cholangiocarcinoma enrolled randomly underwent either rfa combined biliary stenting rfa stent group n 32 biliary stent stent group n 33 overall survival time stent patency period postoperative adverse events recorded results 21 month follow period overall mean survival time significantly longer rfa stent group stent group 13 2 0 6 vs 8 3 0 5 months p 0 001 mean stent patency period rfa stent group also significantly longer stent group 6 8 vs 3 4 months p 0 02 significant difference incidence postoperative adverse events two groups 6 3 2 32 vs 9 1 3 33 p 0 67 conclusion endoscopic rfa combined stenting significantly prolong survival stent patency period without increasing incidence adverse events patients extrahepatic cholangiocarcinoma patient except bismuth type iii iv hilar cholangiocarcinoma approach considered safe effective palliative treatment patients stn","probabilities":0.9799733,"Title":"Endoscopic Biliary Radiofrequency Ablation Prolong The Survival Of Patients With Unrespectable Extrahepatic Cholangiocarcinoma","Abstract":"Background: Endoscopic placement of biliary stents to relieve jaundice is the main palliative treatment for unresectable extrahepatic cholangiocarcinoma. Endoscopic biliary radiofrequency ablation (RFA) has been reported to prolong stent patency, which may be beneficial in improving patient survival. However, available evidence is still insufficient, as most reported studies are retrospective case series. The aim of this study was to explore the clinical effect and safety of RFA in patients with unresectable extrahepatic cholangiocarcinoma. \r\n\r\n Methods: 65 patients with unresectable extrahepatic cholangiocarcinoma, except Bismuth type III and IV hilar cholangiocarcinoma, were enrolled and randomly underwent either RFA combined with biliary stenting (RFA + stent group; n = 32) or biliary stent only (stent-only group; n = 33). Overall survival time, stent patency period, and postoperative adverse events were recorded. \r\n\r\n Results: In the 21-month follow-up period, the overall mean survival time was significantly longer in the RFA + stent group than in the stent-only group (13.2 ± 0.6 vs. 8.3 ± 0.5 months; P < 0.001). The mean stent patency period of the RFA + stent group was also significantly longer than that of the stent-only group (6.8 vs. 3.4 months; P = 0.02). There was no significant difference in the incidence of postoperative adverse events between the two groups (6.3 % [2/32] vs. 9.1 % [3/33]; P = 0.67). \r\n\r\n Conclusion: Endoscopic RFA combined with stenting can significantly prolong survival and the stent patency period without increasing the incidence of adverse events in patients with extrahepatic cholangiocarcinoma patient, except Bismuth type III and IV hilar cholangiocarcinoma. This approach can be considered as a safe and effective palliative treatment for these patients.","Source":"STN","category":"HUMAN","training_data":"Endoscopic Biliary Radiofrequency Ablation Prolong The Survival Of Patients With Unrespectable Extrahepatic Cholangiocarcinoma Background: Endoscopic placement of biliary stents to relieve jaundice is the main palliative treatment for unresectable extrahepatic cholangiocarcinoma. Endoscopic biliary radiofrequency ablation (RFA) has been reported to prolong stent patency, which may be beneficial in improving patient survival. However, available evidence is still insufficient, as most reported studies are retrospective case series. The aim of this study was to explore the clinical effect and safety of RFA in patients with unresectable extrahepatic cholangiocarcinoma. \r\n\r\n Methods: 65 patients with unresectable extrahepatic cholangiocarcinoma, except Bismuth type III and IV hilar cholangiocarcinoma, were enrolled and randomly underwent either RFA combined with biliary stenting (RFA + stent group; n = 32) or biliary stent only (stent-only group; n = 33). Overall survival time, stent patency period, and postoperative adverse events were recorded. \r\n\r\n Results: In the 21-month follow-up period, the overall mean survival time was significantly longer in the RFA + stent group than in the stent-only group (13.2 ± 0.6 vs. 8.3 ± 0.5 months; P < 0.001). The mean stent patency period of the RFA + stent group was also significantly longer than that of the stent-only group (6.8 vs. 3.4 months; P = 0.02). There was no significant difference in the incidence of postoperative adverse events between the two groups (6.3 % [2/32] vs. 9.1 % [3/33]; P = 0.67). \r\n\r\n Conclusion: Endoscopic RFA combined with stenting can significantly prolong survival and the stent patency period without increasing the incidence of adverse events in patients with extrahepatic cholangiocarcinoma patient, except Bismuth type III and IV hilar cholangiocarcinoma. This approach can be considered as a safe and effective palliative treatment for these patients. STN","prediction_labels":"HUMAN"},{"cleaned":"slug inhibition upregulates radiation induced puma activity leading apoptosis cholangiocarcinomas resistance cholangiocarcinoma irradiation therapy major problem cancer treatment slug snail family transcription factor suppressor puma p53 upregulated modulator apoptosis shown involved control apoptosis study investigated whether modulation slug expression using adeno associated virus mediated transfer sirna targeting slug gene raav2 slug sirna affects cholangiocarcinoma sensitivity radiation present study used raav2 slug sirna downregulate expression slug qbc939 cholangiocarcinoma cell lines vitro irradiation vivo studies done orthotopic cholangiocarcinoma radiosensitivity evaluated vitro vivo raav2 slug sirna transfection resulted downregulation levels slug qbc939 cells addition raav2 slug sirna combination radiation increased levels puma contributes radiosensitivity cholangiocarcinomas finally treatment raav2 slug sirna plus irradiation completely regressed tumor growth orthotopic cholangiocarcinomas model summary integrating gene therapy radiotherapy synergistic effect thereby improving survival patients cholangiocarcinomas stn","probabilities":0.9467213,"Title":"Slug Inhibition Upregulates Radiation-Induced Puma Activity Leading To Apoptosis In Cholangiocarcinomas","Abstract":"Resistance of cholangiocarcinoma to irradiation therapy is a major problem in cancer treatment. Slug, a snail family transcription factor, is a suppressor of PUMA (p53 upregulated modulator of apoptosis), which has been shown to be involved in the control of apoptosis. In this study, we investigated whether the modulation of Slug expression, using adeno-associated-virus-mediated transfer of siRNA targeting Slug gene (rAAV2-Slug siRNA), affects cholangiocarcinoma sensitivity to radiation. In the present study, we used rAAV2-Slug siRNA to downregulate the expression of Slug in QBC939 cholangiocarcinoma cell lines in vitro before γ-irradiation. In vivo studies were done with orthotopic cholangiocarcinoma, and radiosensitivity was evaluated both in vitro and in vivo. rAAV2-Slug siRNA transfection resulted in downregulation of the levels of Slug in QBC939 cells. In addition, rAAV2-Slug siRNA, in combination with radiation, increased levels of the PUMA, which contributes to the radiosensitivity of cholangiocarcinomas. Finally, treatment with rAAV2-Slug siRNA plus γ-irradiation completely regressed tumor growth in orthotopic cholangiocarcinomas model. In summary, integrating gene therapy with radiotherapy could have a synergistic effect, thereby improving the survival of patients with cholangiocarcinomas.","Source":"STN","category":"ANIMAL","training_data":"Slug Inhibition Upregulates Radiation-Induced Puma Activity Leading To Apoptosis In Cholangiocarcinomas Resistance of cholangiocarcinoma to irradiation therapy is a major problem in cancer treatment. Slug, a snail family transcription factor, is a suppressor of PUMA (p53 upregulated modulator of apoptosis), which has been shown to be involved in the control of apoptosis. In this study, we investigated whether the modulation of Slug expression, using adeno-associated-virus-mediated transfer of siRNA targeting Slug gene (rAAV2-Slug siRNA), affects cholangiocarcinoma sensitivity to radiation. In the present study, we used rAAV2-Slug siRNA to downregulate the expression of Slug in QBC939 cholangiocarcinoma cell lines in vitro before γ-irradiation. In vivo studies were done with orthotopic cholangiocarcinoma, and radiosensitivity was evaluated both in vitro and in vivo. rAAV2-Slug siRNA transfection resulted in downregulation of the levels of Slug in QBC939 cells. In addition, rAAV2-Slug siRNA, in combination with radiation, increased levels of the PUMA, which contributes to the radiosensitivity of cholangiocarcinomas. Finally, treatment with rAAV2-Slug siRNA plus γ-irradiation completely regressed tumor growth in orthotopic cholangiocarcinomas model. In summary, integrating gene therapy with radiotherapy could have a synergistic effect, thereby improving the survival of patients with cholangiocarcinomas. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic value risk stratification residual disease patients incidental gallbladder cancer background aim given poor prognosis patients residual disease rd re resection specimen incidental gallbladder carcinoma igbc benefit better selection surgical treatment gallbladder cancer risk score gbrs proposed preoperatively identify rd risk precisely stage alone aim study assess prognostic value rd validate gbrs retrospective series patients material methods prospectively collected database including 59 patients igbc diagnosed december 1996 november 2015 retrospectively analyzed three locations rd established local regional distant effect rd overall survival os analyzed kaplan meier method identify variables associated presence rd characteristics patients without rd compared using fisher exact test relative risk rd associated clinical pathologic factors studied univariate logistic regression analysis results rd found 30 patients 50 8 presence rd location associated worse os 29 vs 74 2 p 0 0001 even r0 resection 37 7 vs 74 2 p 0 003 significant difference survival patients without rd local rd 74 2 vs 64 3 p 0 266 patients regional rd distant rd 16 1 vs 20 p 0 411 selecting patients r0 resection achieved n 44 5 year survival rate patients without rd local rd regional rd respectively 74 2 75 13 9 p 0 0001 gbrs calculated 25 cases 42 3 usefulness predict presence regional distant rd rdrd confirmed 80 high risk patients 30 intermediate risk p 0 041 conclusion rdrd local rd represents negative prognostic factor os gbrs useful preoperatively identify patients high risk rdrd r0 resection improve os patients regional rd stn","probabilities":0.9799733,"Title":"Prognostic Value And Risk Stratification Of Residual Disease In Patients With Incidental Gallbladder Cancer","Abstract":"Background and aim: Given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than T-stage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients. \r\n\r\n Material and methods: A prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher's exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis. \r\n\r\n Results: RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041). \r\n\r\n Conclusion: RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD.","Source":"STN","category":"HUMAN","training_data":"Prognostic Value And Risk Stratification Of Residual Disease In Patients With Incidental Gallbladder Cancer Background and aim: Given their poor prognosis, patients with residual disease (RD) in the re-resection specimen of an incidental gallbladder carcinoma (IGBC) could benefit from a better selection for surgical treatment. The Gallbladder Cancer Risk Score (GBRS) has been proposed to preoperatively identify RD risk more precisely than T-stage alone. The aim of this study was to assess the prognostic value of RD and to validate the GBRS in a retrospective series of patients. \r\n\r\n Material and methods: A prospectively collected database including 59 patients with IGBC diagnosed from December 1996 to November 2015 was retrospectively analyzed. Three locations of RD were established: local, regional, and distant. The effect of RD on overall survival (OS) was analyzed with the Kaplan-Meier method. To identify variables associated with the presence of RD, characteristics of patients with and without RD were compared using Fisher's exact test. The relative risk of RD associated with clinical and pathologic factors was studied with a univariate logistic regression analysis. \r\n\r\n Results: RD was found in 30 patients (50.8%). The presence of RD in any location was associated with worse OS (29% vs. 74.2%, p = 0.0001), even after an R0 resection (37.7% vs 74.2%, p = 0.003). There was no significant difference in survival between patients without RD and with local RD (74.2% vs 64.3%, p = 0.266), nor between patients with regional RD and distant RD (16.1% vs 20%, p = 0.411). After selecting patients in which R0 resection was achieved (n = 44), 5-year survival rate for patients without RD, local RD, and regional RD was, respectively, 74.2%, 75%, and 13.9% (p = 0.0001). The GBRS could be calculated in 25 cases (42.3%), and its usefulness to predict the presence of regional or distant RD (RDRD) was confirmed (80% in high-risk patients and 30% in intermediate risk p = 0.041). \r\n\r\n Conclusion: RDRD, but not local RD, represents a negative prognostic factor of OS. The GBRS was useful to preoperatively identify patients with high risk of RDRD. An R0 resection did not improve OS of patients with regional RD. STN","prediction_labels":"HUMAN"},{"cleaned":"validation mayo clinic staging system determining prognoses patients perihilar cholangiocarcinoma background aims systems staging perihilar cholangiocarcinoma phc developed minority patients resectable disease recently developed mayo clinic system staging phc requires clinical radiologic variables yet validated performed retrospective study validate mayo clinic staging system methods identified consecutive patients suspected phc evaluated treated 2 tertiary centers netherlands january 2002 december 2014 baseline characteristics performance status carbohydrate antigen 19 9 level used staging system collected medical records imaging parameters tumor size suspected vascular involvement metastatic disease reassessed 2 experienced abdominal radiologists overall survival analyzed using kaplan meier method comparison staging groups performed using log rank test cox proportional hazard regression analysis discriminative performance quantified concordance index compared radiologic tnm staging american joint committee cancer 7th ed results phcs 600 patients staged according mayo clinic model 23 stage 80 stage ii 357 stage iii 140 stage iv median overall survival time 11 6 months median overall survival times patients stages ii iii iv 33 2 months 19 7 months 12 1 months 6 0 months respectively hazard ratios 1 0 reference 2 02 95 confidence interval ci 1 14 3 58 2 71 95 ci 1 59 4 64 4 00 95 ci 2 30 6 95 respectively p 001 concordance index score 0 59 entire cohort 95 ci 0 56 0 61 mayo clinic model performed slightly better radiologic american joint committee cancer tnm system conclusions retrospective study 600 patients phc validated mayo clinic system staging phc 4 tier staging system may aid clinicians making treatment decisions referral surgery predicting survival times pubmed","probabilities":0.9799733,"Title":"Validation of the Mayo Clinic Staging System in Determining Prognoses of Patients With Perihilar Cholangiocarcinoma","Abstract":"BACKGROUND & AIMS: Most systems for staging perihilar cholangiocarcinoma (PHC) have been developed for the minority of patients with resectable disease. The recently developed Mayo Clinic system for staging PHC requires only clinical and radiologic variables, but has not yet been validated. We performed a retrospective study to validate the Mayo Clinic staging system. METHODS: We identified consecutive patients with suspected PHC who were evaluated and treated at 2 tertiary centers in The Netherlands, from January 2002 through December 2014. Baseline characteristics (performance status, carbohydrate antigen 19-9 level) used in the staging system were collected from medical records and imaging parameters (tumor size, suspected vascular involvement, and metastatic disease) were reassessed by 2 experienced abdominal radiologists. Overall survival was analyzed using the Kaplan-Meier method and comparison of staging groups was performed using the log-rank test and Cox proportional hazard regression analysis. Discriminative performance was quantified by the concordance index and compared with the radiologic TNM staging of the American Joint Committee on Cancer (7th ed). RESULTS: PHCs from 600 patients were staged according to the Mayo Clinic model (23 stage I, 80 stage II, 357 stage III, and 140 stage IV). The median overall survival time was 11.6 months. The median overall survival times for patients with stages I, II, III, and IV were 33.2 months, 19.7 months, 12.1 months, and 6.0 months, respectively; with hazard ratios of 1.0 (reference), 2.02 (95% confidence interval [CI], 1.14-3.58), 2.71 (95% CI, 1.59-4.64), and 4.00 (95% CI, 2.30-6.95), respectively (P < .001). The concordance index score was 0.59 for the entire cohort (95% CI, 0.56-0.61). The Mayo Clinic model performed slightly better than the radiologic American Joint Committee on Cancer TNM system. CONCLUSIONS: In a retrospective study of 600 patients with PHC, we validated the Mayo Clinic system for staging PHC. This 4-tier staging system may aid clinicians in making treatment decisions, such as referral for surgery, and predicting survival times.","Source":"PubMed","category":"HUMAN","training_data":"Validation of the Mayo Clinic Staging System in Determining Prognoses of Patients With Perihilar Cholangiocarcinoma BACKGROUND & AIMS: Most systems for staging perihilar cholangiocarcinoma (PHC) have been developed for the minority of patients with resectable disease. The recently developed Mayo Clinic system for staging PHC requires only clinical and radiologic variables, but has not yet been validated. We performed a retrospective study to validate the Mayo Clinic staging system. METHODS: We identified consecutive patients with suspected PHC who were evaluated and treated at 2 tertiary centers in The Netherlands, from January 2002 through December 2014. Baseline characteristics (performance status, carbohydrate antigen 19-9 level) used in the staging system were collected from medical records and imaging parameters (tumor size, suspected vascular involvement, and metastatic disease) were reassessed by 2 experienced abdominal radiologists. Overall survival was analyzed using the Kaplan-Meier method and comparison of staging groups was performed using the log-rank test and Cox proportional hazard regression analysis. Discriminative performance was quantified by the concordance index and compared with the radiologic TNM staging of the American Joint Committee on Cancer (7th ed). RESULTS: PHCs from 600 patients were staged according to the Mayo Clinic model (23 stage I, 80 stage II, 357 stage III, and 140 stage IV). The median overall survival time was 11.6 months. The median overall survival times for patients with stages I, II, III, and IV were 33.2 months, 19.7 months, 12.1 months, and 6.0 months, respectively; with hazard ratios of 1.0 (reference), 2.02 (95% confidence interval [CI], 1.14-3.58), 2.71 (95% CI, 1.59-4.64), and 4.00 (95% CI, 2.30-6.95), respectively (P < .001). The concordance index score was 0.59 for the entire cohort (95% CI, 0.56-0.61). The Mayo Clinic model performed slightly better than the radiologic American Joint Committee on Cancer TNM system. CONCLUSIONS: In a retrospective study of 600 patients with PHC, we validated the Mayo Clinic system for staging PHC. This 4-tier staging system may aid clinicians in making treatment decisions, such as referral for surgery, and predicting survival times. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance angiogenesis chalkley counting node negative cancer ampulla vater angiogenesis essential tumor growth metastasis currently chalkley assay cd34 immunostaining proposed standard method angiogenesis quantification solid tumor sections purpose study evaluate expression cd34 prognostic significance using chalkley method node negative carcinoma ampulla vater january 1997 december 2006 56 node negative patients curative resection carcinoma ampulla vater retrospectively reviewed chalkley count expressed mean value three counts tumor divided two groups according mean value chalkley count low 4 high 4 mean chalkley count value 4 0 3 1 low chalkley group 1 3 yr recurrence rates 18 3 47 6 respectively high chalkley group 1 3 yr recurrence rates 26 5 60 6 respectively high chalkley count statistical significance factor recurrence node negative ampulla vater carcinoma assessment angiogenesis may important role prognostic evaluation node negative cancer ampulla vater pubmed","probabilities":0.9799733,"Title":"Prognostic significance of angiogenesis by Chalkley counting in node negative cancer of the ampulla of Vater","Abstract":"Angiogenesis is essential for tumor growth and metastasis. Currently, the Chalkley assay with CD34 immunostaining is the proposed standard method for angiogenesis quantification in solid tumor sections. The purpose of this study was to evaluate the expression of CD34 and its prognostic significance using the Chalkley method in node negative carcinoma of the ampulla of Vater. Between January 1997 and December 2006, 56 node negative patients who had curative resection for carcinoma of the ampulla of Vater were retrospectively reviewed. The Chalkley count was expressed as the mean value of the three counts for each tumor and further divided into two groups according to the mean value of the Chalkley count: low < 4 or high ≥ 4. The mean Chalkley count value was 4.0 (± 3.1). In the low Chalkley group, the 1- and 3-yr recurrence rates were 18.3%, 47.6% respectively; in the high Chalkley group, the 1- and 3-yr recurrence rates were 26.5% and 60.6% respectively. Only high Chalkley count had statistical significance as a factor in recurrence of node negative ampulla of Vater carcinoma. Assessment of angiogenesis may have an important role in the prognostic evaluation of node negative cancer of the ampulla of Vater.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of angiogenesis by Chalkley counting in node negative cancer of the ampulla of Vater Angiogenesis is essential for tumor growth and metastasis. Currently, the Chalkley assay with CD34 immunostaining is the proposed standard method for angiogenesis quantification in solid tumor sections. The purpose of this study was to evaluate the expression of CD34 and its prognostic significance using the Chalkley method in node negative carcinoma of the ampulla of Vater. Between January 1997 and December 2006, 56 node negative patients who had curative resection for carcinoma of the ampulla of Vater were retrospectively reviewed. The Chalkley count was expressed as the mean value of the three counts for each tumor and further divided into two groups according to the mean value of the Chalkley count: low < 4 or high ≥ 4. The mean Chalkley count value was 4.0 (± 3.1). In the low Chalkley group, the 1- and 3-yr recurrence rates were 18.3%, 47.6% respectively; in the high Chalkley group, the 1- and 3-yr recurrence rates were 26.5% and 60.6% respectively. Only high Chalkley count had statistical significance as a factor in recurrence of node negative ampulla of Vater carcinoma. Assessment of angiogenesis may have an important role in the prognostic evaluation of node negative cancer of the ampulla of Vater. PubMed","prediction_labels":"HUMAN"},{"cleaned":"polymorphism growth factors survival gall bladder cancer abstract available google scholar","probabilities":0.9799733,"Title":"Polymorphism Of Growth Factors And Survival In Gall Bladder Cancer","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Polymorphism Of Growth Factors And Survival In Gall Bladder Cancer Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"expression fibroblast activation protein clinicopathological relevance distal cholangiocarcinoma objectives current survival patients distal cholangiocarcinoma dcca poor need develop new prognostic predictive biomarkers improve survival patients fibroblast activation protein fap expression associated survival several solid malignancies goal study evaluate expression pattern prognostic significance fap dcca materials methods fap expression examined 57 resected dcca specimens 28 paired lymph node metastasis specimens well 10 benign bile ducts using immunohistochemistry fap expression scored epithelial stromal component dcca specimens association fap expression prognosis evaluated using univariable multivariable statistical modeling results fap expression absent benign controls fap expression evident epithelial 43 75 stromal compartment 34 60 dcca association epithelial stromal fap expression clinicopathological factors epithelial fap expression hr 0 4 95 ci 0 20 0 78 p 007 stromal fap expression significantly associated better survival univariable multivariable analysis conclusions fap overexpression evident dcca positive association epithelial fap expression better survival merits evaluation stn","probabilities":0.9799733,"Title":"Expression Of Fibroblast Activation Protein And The Clinicopathological Relevance In Distal Cholangiocarcinoma","Abstract":"Objectives: The current survival of patients with distal cholangiocarcinoma (dCCA) is poor. There is a need to develop new prognostic and predictive biomarkers to improve the survival of patients. Fibroblast activation protein (FAP) expression has been associated with survival in several solid malignancies. The goal of this study was to evaluate the expression pattern and prognostic significance of FAP in dCCA.Materials and methods: FAP expression was examined in 57 resected dCCA specimens and 28 paired lymph node metastasis specimens, as well as 10 benign bile ducts using immunohistochemistry. FAP expression was scored in the epithelial and stromal component of the dCCA specimens. The association between FAP expression and prognosis was evaluated using univariable and multivariable statistical modeling.Results: FAP expression was absent in the benign controls. FAP expression was evident in the epithelial 43 (75%) and stromal compartment 34 (60%) of dCCA. There was no association between epithelial or stromal FAP expression and clinicopathological factors. Epithelial FAP expression (HR 0.4 95% CI 0.20-0.78; p=.007) but not stromal FAP expression was significantly associated with better survival in univariable and multivariable analysis.Conclusions: FAP overexpression is evident in dCCA. There was a positive association between epithelial FAP expression and better survival which merits further evaluation.","Source":"STN","category":"ANIMAL","training_data":"Expression Of Fibroblast Activation Protein And The Clinicopathological Relevance In Distal Cholangiocarcinoma Objectives: The current survival of patients with distal cholangiocarcinoma (dCCA) is poor. There is a need to develop new prognostic and predictive biomarkers to improve the survival of patients. Fibroblast activation protein (FAP) expression has been associated with survival in several solid malignancies. The goal of this study was to evaluate the expression pattern and prognostic significance of FAP in dCCA.Materials and methods: FAP expression was examined in 57 resected dCCA specimens and 28 paired lymph node metastasis specimens, as well as 10 benign bile ducts using immunohistochemistry. FAP expression was scored in the epithelial and stromal component of the dCCA specimens. The association between FAP expression and prognosis was evaluated using univariable and multivariable statistical modeling.Results: FAP expression was absent in the benign controls. FAP expression was evident in the epithelial 43 (75%) and stromal compartment 34 (60%) of dCCA. There was no association between epithelial or stromal FAP expression and clinicopathological factors. Epithelial FAP expression (HR 0.4 95% CI 0.20-0.78; p=.007) but not stromal FAP expression was significantly associated with better survival in univariable and multivariable analysis.Conclusions: FAP overexpression is evident in dCCA. There was a positive association between epithelial FAP expression and better survival which merits further evaluation. STN","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder carcinoma discovered laparoscopic cholecystectomy identifying patients benefit reoperation background despite early radical reoperation recurrence poor survival observed 40 patients incidentally discovered gallbladder carcinoma gbc undergoing laparoscopic cholecystectomy lc study seeks identify prognostic factors re gbc resection methods retrospective review prospectively maintained patient database patients undergoing resection gbc january 1995 march 2017 performed prognostic factors survival assessed multivariate cox analysis results 50 consecutive patients median age 64 years range 38 82 undergoing reoperation 45 30 days lc re resection entailed major hepatectomy five patients 10 lymphadenectomy patients ninety day morbidity mortality 22 2 respectively lymph node ln involvement present 24 48 patients mean 5 79 14 4 ln median overall survival 40 months 1 3 5 10 year survival rates 80 50 41 36 respectively independent risk factors overall survival t3 tumours hr 7 58 95 confidence intervals ci 2 41 23 83 ln involvement hr 3 66 95 ci 1 42 9 45 patients presenting zero one two risk factors 3 year survival rates 85 31 0 respectively median overall survival 80 22 13 months respectively p 0 0001 conclusions gbc discovery following lc t3 tumours tumours ln characterised poor prognosis presence identification prognostic factors help identify patients need alternative perioperative treatments pubmed","probabilities":0.9799733,"Title":"Incidental Gallbladder Carcinoma Discovered after Laparoscopic Cholecystectomy: Identifying Patients Who will Benefit from Reoperation","Abstract":"BACKGROUND: Despite an early radical reoperation, recurrence and poor survival are observed in up to 40% of patients with an incidentally discovered gallbladder carcinoma (I-GBC) after undergoing a laparoscopic cholecystectomy (LC). This study seeks to identify prognostic factors after re-I-GBC resection. METHODS: A retrospective review of a prospectively maintained patient database with patients who were undergoing resection for I-GBC from January 1995 to March 2017 was performed. Prognostic factors for survival were assessed by multivariate Cox analysis. RESULTS: There were 50 consecutive patients (median age 64 years; range 38-82) undergoing reoperation 45 ± 30 days after LC. Re-resection entailed a major hepatectomy in five patients (10%) and lymphadenectomy in all patients. Ninety-day morbidity and mortality were 22 and 2%, respectively. Lymph node (LN) involvement was present in 24 (48%) patients with a mean of 5.79 ± 14.4 LN+. Median overall survival was 40 months with 1-, 3-, 5- and 10-year survival rates of 80, 50, 41 and 36%, respectively. Independent risk factors for overall survival were T3 tumours (HR = 7.58; 95% confidence intervals (CI), 2.41-23.83.) and LN involvement (HR = 3.66; 95% CI, 1.42-9.45). Patients presenting with zero, one and two risk factors had 3-year survival rates of 85, 31 and 0%, respectively, and median overall survival of 80, 22 and 13 months, respectively (p < 0.0001). CONCLUSIONS: After I-GBC discovery following an LC, T3 tumours and tumours with LN+ are characterised by poor prognosis. The presence and the identification of these prognostic factors help identify patients in need of alternative perioperative treatments.","Source":"PubMed","category":"HUMAN","training_data":"Incidental Gallbladder Carcinoma Discovered after Laparoscopic Cholecystectomy: Identifying Patients Who will Benefit from Reoperation BACKGROUND: Despite an early radical reoperation, recurrence and poor survival are observed in up to 40% of patients with an incidentally discovered gallbladder carcinoma (I-GBC) after undergoing a laparoscopic cholecystectomy (LC). This study seeks to identify prognostic factors after re-I-GBC resection. METHODS: A retrospective review of a prospectively maintained patient database with patients who were undergoing resection for I-GBC from January 1995 to March 2017 was performed. Prognostic factors for survival were assessed by multivariate Cox analysis. RESULTS: There were 50 consecutive patients (median age 64 years; range 38-82) undergoing reoperation 45 ± 30 days after LC. Re-resection entailed a major hepatectomy in five patients (10%) and lymphadenectomy in all patients. Ninety-day morbidity and mortality were 22 and 2%, respectively. Lymph node (LN) involvement was present in 24 (48%) patients with a mean of 5.79 ± 14.4 LN+. Median overall survival was 40 months with 1-, 3-, 5- and 10-year survival rates of 80, 50, 41 and 36%, respectively. Independent risk factors for overall survival were T3 tumours (HR = 7.58; 95% confidence intervals (CI), 2.41-23.83.) and LN involvement (HR = 3.66; 95% CI, 1.42-9.45). Patients presenting with zero, one and two risk factors had 3-year survival rates of 85, 31 and 0%, respectively, and median overall survival of 80, 22 and 13 months, respectively (p < 0.0001). CONCLUSIONS: After I-GBC discovery following an LC, T3 tumours and tumours with LN+ are characterised by poor prognosis. The presence and the identification of these prognostic factors help identify patients in need of alternative perioperative treatments. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radiofrequency ablation hepatic metastases curative resection extrahepatic cholangiocarcinoma objective objective study retrospectively evaluate local control survival radiofrequency ablation rfa patients liver metastases arising extrahepatic cholangiocarcinoma previously undergone curative resection materials methods may 2003 may 2009 rfa using internally cooled electrode performed 29 metachronous liver metastases mean number tumors per patient 1 6 arising extrahepatic cholangiocarcinoma 18 patients mean age 66 years tumor size ranged 0 9 4 6 cm maximum dimension mean 2 3 cm historical comparisons included 24 patients diagnosed recurrent metastasis limited liver february 1997 april 2003 met inclusion criteria rfa 16 patients received supportive therapy eight patients underwent chemotherapy without radiation results five patients major complications liver abscess n 4 patients biliary stricture n 1 17 per treatment complication rate 5 29 procedure related deaths complete tumor necrosis achieved 29 tumors one session rfa local tumor progression rate 38 median time detection 5 months first diagnosis liver metastasis median overall survival 12 4 months 3 year survival rate 10 patients received rfa lived significantly longer patients received chemoradiotherapy median survival 5 6 months received supportive treatment median survival 5 3 months p 0 001 conclusion percutaneous rfa results effective local tumor control may prolong survival patients recurrent hepatic metastases curative resection extrahepatic cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Radiofrequency ablation of hepatic metastases after curative resection of extrahepatic cholangiocarcinoma","Abstract":"OBJECTIVE: The objective of our study was to retrospectively evaluate local control and survival after radiofrequency ablation (RFA) in patients with liver metastases arising from extrahepatic cholangiocarcinoma who had previously undergone curative resection. MATERIALS AND METHODS: From May 2003 to May 2009, RFA using an internally cooled electrode was performed on 29 metachronous liver metastases (mean number of tumors per patient, 1.6) arising from extrahepatic cholangiocarcinoma in 18 patients (mean age, 66 years). Tumor size ranged from 0.9 to 4.6 cm in maximum dimension (mean, 2.3 cm). As historical comparisons, we included 24 patients diagnosed with recurrent metastasis limited to the liver between February 1997 and April 2003 and who met the inclusion criteria for RFA: 16 patients received supportive therapy only and eight patients underwent chemotherapy with or without radiation. RESULTS: Five patients had major complications (liver abscess, n = 4 patients; biliary stricture, n = 1; 17% per-treatment complication rate [5/29]), but there were no procedure-related deaths. Complete tumor necrosis was achieved in all 29 tumors after one session of RFA. The local tumor progression rate was 38% (median time to detection, 5 months). From the first diagnosis of liver metastasis, the median overall survival was 12.4 months and the 3-year survival rate was 10%. Patients who received RFA lived significantly longer than patients who received chemoradiotherapy (median survival, 5.6 months) and those who received supportive treatment (median survival, 5.3 months) (p < 0.001). CONCLUSION: Percutaneous RFA results in effective local tumor control and may prolong survival in patients with recurrent hepatic metastases after curative resection for extrahepatic cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Radiofrequency ablation of hepatic metastases after curative resection of extrahepatic cholangiocarcinoma OBJECTIVE: The objective of our study was to retrospectively evaluate local control and survival after radiofrequency ablation (RFA) in patients with liver metastases arising from extrahepatic cholangiocarcinoma who had previously undergone curative resection. MATERIALS AND METHODS: From May 2003 to May 2009, RFA using an internally cooled electrode was performed on 29 metachronous liver metastases (mean number of tumors per patient, 1.6) arising from extrahepatic cholangiocarcinoma in 18 patients (mean age, 66 years). Tumor size ranged from 0.9 to 4.6 cm in maximum dimension (mean, 2.3 cm). As historical comparisons, we included 24 patients diagnosed with recurrent metastasis limited to the liver between February 1997 and April 2003 and who met the inclusion criteria for RFA: 16 patients received supportive therapy only and eight patients underwent chemotherapy with or without radiation. RESULTS: Five patients had major complications (liver abscess, n = 4 patients; biliary stricture, n = 1; 17% per-treatment complication rate [5/29]), but there were no procedure-related deaths. Complete tumor necrosis was achieved in all 29 tumors after one session of RFA. The local tumor progression rate was 38% (median time to detection, 5 months). From the first diagnosis of liver metastasis, the median overall survival was 12.4 months and the 3-year survival rate was 10%. Patients who received RFA lived significantly longer than patients who received chemoradiotherapy (median survival, 5.6 months) and those who received supportive treatment (median survival, 5.3 months) (p < 0.001). CONCLUSION: Percutaneous RFA results in effective local tumor control and may prolong survival in patients with recurrent hepatic metastases after curative resection for extrahepatic cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance tumor necrosis macrophage invasion hilar cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Prognostic Significance Of Tumor Necrosis And Macrophage Invasion In Hilar Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Significance Of Tumor Necrosis And Macrophage Invasion In Hilar Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"expression analysis s100 calcium binding protein a9 erbb2 gallbladder cancer background gallbladder cancer uncommon malignancy rare neoplasm high incidence north india cholecystectomy way treatment left lack diagnostic biomarker chemotherapy resistant nature make disease fatal therefore improving survival rate gbc patients identification biomarker necessity s100a9 known modulate signal pathways directly promote invasion migration metastasis probably via activation nf kb akt map kinases erbb2 role tyrosine kinase aims objectives aim study analyze expression s100a9 erbb2 order understand likely role gallbladder carcinogenesis material methods approx 70 samples cancers gbc 34 non tumor samples recruited ihc 28 samples methylation study immunohistochemistry carried tissue microarray tma gallbladder cancer tissues compared non tumor tissues bisulfite modification followed ms pcr performed identify promoter methylation 2 analysis performed test statistical significance results ihc revealed underexpression 33 71 cases p 0 6 hypermethylation 14 25 cases p 0 4 s100a9 gbc contrast erbb2 49 74 cases p 0 1 found overexpressed conclusion downregulation upregulation s100a9 erbb2 respectively shown immunohistochemistry ms pcr seem involved progression gbc directly indirectly propose two genes may used diagnostic prognostic biomarkers gbc future therapeutics however results require validation real time pcr large number samples size google scholar","probabilities":0.9285714,"Title":"Expression Analysis Of S100 Calcium Binding Protein A9 And Erbb2 In Gallbladder Cancer","Abstract":"Background: Gallbladder cancer is an uncommon malignancy\nand a rare neoplasm with high incidence in North India.\nCholecystectomy is the only way of treatment left. Lack of\ndiagnostic biomarker(s) and being chemotherapy resistant in\nnature, make this disease fatal. Therefore for improving the\nsurvival rate of GBC patients, identification of biomarker is a\nnecessity. S100A9 is known to modulate signal pathways to\ndirectly promote invasion, migration and metastasis, probably via activation of NF-kB, Akt or MAP kinases and ERBB2\nhas a role as tyrosine kinase. Aims and Objectives: The\naim of this study is to analyze the expression of S100A9\nand ERBB2 in order to understand their likely role in\ngallbladder carcinogenesis. Material and Methods: Approx\n70 samples of cancers (GBC) and 34 of non tumor samples\nwere recruited for IHC and 28 samples for methylation study.\nImmunohistochemistry was carried out on Tissue Microarray\n(TMA) in gallbladder cancer tissues and compared with that\nof non tumor tissues. Bisulfite modification, followed by MS\nPCR, was performed to identify the promoter methylation.\nχ2 analysis was performed to test the statistical significance.\nResults: IHC revealed underexpression (33/71 of cases;\np=0.6) and hypermethylation (14/25 of cases; p=0.4) of\nS100A9 in GBC in contrast ERBB2 (49/74 of cases; p=0.1)\nwas found overexpressed. Conclusion: Downregulation and\nupregulation of S100A9 and ERBB2 respectively were shown\nby immunohistochemistry and MS PCR which seem to be\ninvolved in the progression of GBC directly or indirectly. We\npropose that there two genes may be used as diagnostic and\nprognostic biomarkers for GBC in future therapeutics. However,\nthese results require further validation by Real Time PCR in\nlarge number of samples size.","Source":"Google Scholar","category":"ANIMAL","training_data":"Expression Analysis Of S100 Calcium Binding Protein A9 And Erbb2 In Gallbladder Cancer Background: Gallbladder cancer is an uncommon malignancy\nand a rare neoplasm with high incidence in North India.\nCholecystectomy is the only way of treatment left. Lack of\ndiagnostic biomarker(s) and being chemotherapy resistant in\nnature, make this disease fatal. Therefore for improving the\nsurvival rate of GBC patients, identification of biomarker is a\nnecessity. S100A9 is known to modulate signal pathways to\ndirectly promote invasion, migration and metastasis, probably via activation of NF-kB, Akt or MAP kinases and ERBB2\nhas a role as tyrosine kinase. Aims and Objectives: The\naim of this study is to analyze the expression of S100A9\nand ERBB2 in order to understand their likely role in\ngallbladder carcinogenesis. Material and Methods: Approx\n70 samples of cancers (GBC) and 34 of non tumor samples\nwere recruited for IHC and 28 samples for methylation study.\nImmunohistochemistry was carried out on Tissue Microarray\n(TMA) in gallbladder cancer tissues and compared with that\nof non tumor tissues. Bisulfite modification, followed by MS\nPCR, was performed to identify the promoter methylation.\nχ2 analysis was performed to test the statistical significance.\nResults: IHC revealed underexpression (33/71 of cases;\np=0.6) and hypermethylation (14/25 of cases; p=0.4) of\nS100A9 in GBC in contrast ERBB2 (49/74 of cases; p=0.1)\nwas found overexpressed. Conclusion: Downregulation and\nupregulation of S100A9 and ERBB2 respectively were shown\nby immunohistochemistry and MS PCR which seem to be\ninvolved in the progression of GBC directly or indirectly. We\npropose that there two genes may be used as diagnostic and\nprognostic biomarkers for GBC in future therapeutics. However,\nthese results require further validation by Real Time PCR in\nlarge number of samples size. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"yttrium 90 radioembolization unresectable standard chemorefractory intrahepatic cholangiocarcinoma survival efficacy safety study purpose assess overall survival efficacy safety radioembolization yttrium 90 y90 unresectable standard chemorefractory intrahepatic cholangiocarcinoma icc methods patients unresectable standard chemorefractory icc treated y90 studied survival calculated date first y90 procedure tumor response assessed response evaluation criteria solid tumors criteria follow computed tomography magnetic resonance imaging scans national cancer institute common terminology criteria nci ctcae version 3 used complications statistical analysis performed kaplan meier estimator log rank test results nineteen patients underwent total 24 resin based y90 treatments median survival time diagnosis first y90 procedure 752 193 95 confidence interval ci 374 1130 345 128 95 ci 95 595 days respectively median survival eastern cooperative oncology group ecog performance status 1 n 15 ecog performance status 2 n 4 450 190 95 ci 78 822 345 227 95 ci 0 790 days respectively p 214 patients extrahepatic metastasis n 11 median survival 404 309 95 ci 0 1010 days versus 345 117 95 ci 115 575 days patients without metastasis n 8 p 491 mortality reported within 30 days first y90 radioembolization one patient developed grade 3 thrombocytopenia assessed nci ctcae fatigue transient abdominal pain observed 4 21 6 32 patients respectively conclusion y90 radioembolization effective unresectable standard chemorefractory icc pubmed","probabilities":0.9799733,"Title":"Yttrium-90 radioembolization for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma: survival, efficacy, and safety study","Abstract":"PURPOSE: To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC). METHODS: Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan-Meier estimator by the log rank test. RESULTS: Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 ± 193 [95 % confidence interval (CI) 374-1130] and 345 ± 128 (95 % CI 95-595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 ± 190 (95 % CI 78-822) and 345 ± 227 (95 % CI 0-790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 ± 309 (95 % CI 0-1010) days versus 345 ± 117 (95 % CI 115-575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively. CONCLUSION: Y90 radioembolization is effective for unresectable standard-chemorefractory ICC.","Source":"PubMed","category":"HUMAN","training_data":"Yttrium-90 radioembolization for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma: survival, efficacy, and safety study PURPOSE: To assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC). METHODS: Patients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan-Meier estimator by the log rank test. RESULTS: Nineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 ± 193 [95 % confidence interval (CI) 374-1130] and 345 ± 128 (95 % CI 95-595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 ± 190 (95 % CI 78-822) and 345 ± 227 (95 % CI 0-790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 ± 309 (95 % CI 0-1010) days versus 345 ± 117 (95 % CI 115-575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively. CONCLUSION: Y90 radioembolization is effective for unresectable standard-chemorefractory ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"different carcinogenic process cholangiocarcinoma cases epidemically developing among workers printing company japan recently cholangiocarcinoma epidemically developed among young adult workers printing company japan exposure organic solvents including 1 2 dichloropropane dichloromethane supposed associated carcinoma development metabolism dichloromethane proceeds theta class glutathione transferase gst t1 1 catalyzed pathway reactive intermediates implicated genotoxicity carcinogenicity study examined features carcinogenic process cholangiocarcinoma developed printing company surgically resected specimens cholangiocarcinoma cases analyzed cases associated precursor lesions biliary intraepithelial neoplasia bilin intraductal papillary neoplasm bile duct ipnb immunohistochemical analysis confirmed constitutional expression gst t1 1 normal hepatobiliary tract immunostaining h2ax marker dna double strand break showed expression significantly increased foci bilin ipnb invasive carcinoma well non neoplastic biliary epithelial cells printing company cases compared control groups printing company cases immunohistochemical expression p53 observed non neoplastic biliary epithelial cells bilin 1 mutations kras gnas detected foci bilin one 3 cases printing company results revealed different carcinogenic process printing company cases suggesting exposed organic solvents might act carcinogen biliary epithelial cells causing dna damage thereby contributing carcinoma development stn","probabilities":0.9799733,"Title":"Different Carcinogenic Process In Cholangiocarcinoma Cases Epidemically Developing Among Workers Of A Printing Company In Japan","Abstract":"Recently, cholangiocarcinoma has epidemically developed among young adult workers of a printing company in Japan. Exposure to organic solvents including 1,2-dichloropropane and/or dichloromethane is supposed to be associated with the carcinoma development. The metabolism of dichloromethane proceeds through a Theta-class glutathione S-transferase (GST) T1-1-catalyzed pathway, where its reactive intermediates have been implicated in genotoxicity and carcinogenicity. This study examined features of the carcinogenic process of the cholangiocarcinoma developed in the printing company. Surgically resected specimens of the cholangiocarcinoma cases were analyzed, where all cases were associated with precursor lesions such as biliary intraepithelial neoplasia (BilIN) and/or intraductal papillary neoplasm of the bile duct (IPNB). Immunohistochemical analysis confirmed constitutional expression of GST T1-1 in normal hepatobiliary tract. Immunostaining of γ-H2AX, a marker of DNA double strand break, showed that its expression was significantly increased in foci of BilIN, IPNB and invasive carcinoma as well as in non-neoplastic biliary epithelial cells of the printing company cases when compared to that of control groups. In the printing company cases, immunohistochemical expression of p53 was observed in non-neoplastic biliary epithelial cells and BilIN-1. Mutations of KRAS and GNAS were detected in foci of BilIN in one out of 3 cases of the printing company. These results revealed different carcinogenic process of the printing company cases, suggesting that the exposed organic solvents might act as a carcinogen for biliary epithelial cells by causing DNA damage, thereby contributing to the carcinoma development.","Source":"STN","category":"HUMAN","training_data":"Different Carcinogenic Process In Cholangiocarcinoma Cases Epidemically Developing Among Workers Of A Printing Company In Japan Recently, cholangiocarcinoma has epidemically developed among young adult workers of a printing company in Japan. Exposure to organic solvents including 1,2-dichloropropane and/or dichloromethane is supposed to be associated with the carcinoma development. The metabolism of dichloromethane proceeds through a Theta-class glutathione S-transferase (GST) T1-1-catalyzed pathway, where its reactive intermediates have been implicated in genotoxicity and carcinogenicity. This study examined features of the carcinogenic process of the cholangiocarcinoma developed in the printing company. Surgically resected specimens of the cholangiocarcinoma cases were analyzed, where all cases were associated with precursor lesions such as biliary intraepithelial neoplasia (BilIN) and/or intraductal papillary neoplasm of the bile duct (IPNB). Immunohistochemical analysis confirmed constitutional expression of GST T1-1 in normal hepatobiliary tract. Immunostaining of γ-H2AX, a marker of DNA double strand break, showed that its expression was significantly increased in foci of BilIN, IPNB and invasive carcinoma as well as in non-neoplastic biliary epithelial cells of the printing company cases when compared to that of control groups. In the printing company cases, immunohistochemical expression of p53 was observed in non-neoplastic biliary epithelial cells and BilIN-1. Mutations of KRAS and GNAS were detected in foci of BilIN in one out of 3 cases of the printing company. These results revealed different carcinogenic process of the printing company cases, suggesting that the exposed organic solvents might act as a carcinogen for biliary epithelial cells by causing DNA damage, thereby contributing to the carcinoma development. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance tumor necrosis hilar cholangiocarcinoma background tumor necrosis peritumoral fibrosis suggested prognostic value selected solid tumors however little known regarding influence tumor progression prognosis hilar cholangiocarcinoma hc methods surgically resected tumor specimens hc n 47 analyzed formation necrosis extent peritumoral fibrosis tumor necrosis grade fibrosis assessed histologically correlated clinicopathological characteristics tumor recurrence patients survival univariate kaplan meier analysis stepwise multivariable cox regression model applied results mild peritumoral fibrosis evident 12 tumor samples moderate peritumoral fibrosis 20 high grade fibrosis 15 necrosis evident 19 47 tumor samples patients tumors characterized necrosis showed significantly decreased 5 year recurrence free survival 37 9 vs 25 7 p 05 significantly decreased 5 year overall survival 42 6 vs 12 4 p 05 compared patients tumors showing necrosis r status tumor recurrence tumor necrosis prognostic value univariate analysis p 05 multivariate survival analysis confirmed tumor necrosis p 038 independent prognostic variable conclusions assessment tumor necrosis appears valuable additional prognostic tool routine histopathological evaluation hc observations might implications monitoring individualized multimodal therapeutic strategies pubmed","probabilities":0.9799733,"Title":"Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma","Abstract":"BACKGROUND: Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). METHODS: Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. RESULTS: Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. CONCLUSIONS: The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Significance of Tumor Necrosis in Hilar Cholangiocarcinoma BACKGROUND: Tumor necrosis and peritumoral fibrosis have both been suggested to have a prognostic value in selected solid tumors. However, little is known regarding their influence on tumor progression and prognosis in hilar cholangiocarcinoma (HC). METHODS: Surgically resected tumor specimens of HC (n = 47) were analyzed for formation of necrosis and extent of peritumoral fibrosis. Tumor necrosis and grade of fibrosis were assessed histologically and correlated with clinicopathological characteristics, tumor recurrence, and patients' survival. Univariate Kaplan-Meier analysis and a stepwise multivariable Cox regression model were applied. RESULTS: Mild peritumoral fibrosis was evident in 12 tumor samples, moderate peritumoral fibrosis in 20, and high-grade fibrosis in 15. Necrosis was evident in 19 of 47 tumor samples. Patients with tumors characterized by necrosis showed a significantly decreased 5-year recurrence-free survival (37.9 vs. 25.7 %; p < .05) and a significantly decreased 5-year overall survival (42.6 vs. 12.4 %; p < .05), when compared with patients with tumors showing no necrosis. R status, tumor recurrence, and tumor necrosis were of prognostic value in the univariate analysis (all p < .05). Multivariate survival analysis confirmed tumor necrosis (p = .038) as the only independent prognostic variable. CONCLUSIONS: The assessment of tumor necrosis appears as a valuable additional prognostic tool in routine histopathological evaluation of HC. These observations might have implications for monitoring and more individualized multimodal therapeutic strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prevalence gallbladder carcinoma among patients chronic cholecystitis cholelithiasis undergoing cholecystectomy gallbladder carcinoma lethal disease aggressiveness advanced stage presentation early detection gallbladder carcinoma difficult nonspecific symptoms stone chronic inflammation important risk factors exact picture frequency gallbladder carcinoma detected cholecystectomy specimen patients chronic cholecystitis cholelithiasis clear unknown early diagnosis prompt surgery gallstone disease may allow discovery deadly disease earlier stage simple cholecystectomy curative treatment determine frequency gallbladder carcinoma patients undergoing cholecystectomy cholelithiasis evaluation sociodemographic behavioral risk factors two hundred forty consecutive patients chronic cholecystitis due cholelithiasis admitted cholecystectomy dept surgery north bengal medical college darjeeling period february 2011 january 2012 included study detailed history examination findings histopathology reports noted cases histopathologically confirmed carcinoma gallbladders evaluated descriptive statistics 240 patients undergoing cholecystectomy 185 77 1 females 55 22 9 males highest incidence chronic cholecystitis cholelithiasis 34 43 years age group 29 2 multiple stones found 91 3 cases duration disease patients 2 4 years five patients 240 incidental gallbladder carcinoma 4 5 gallbladder carcinoma patients duration gallstone disease 10 years pt1 stage prompt cholecystectomy symptomatic gallstone disease patients effective secondary prevention detection treatment gallbladder carcinoma early treatable stage google scholar","probabilities":0.9799733,"Title":"Prevalence Of Gallbladder Carcinoma Among The Patients Of Chronic Cholecystitis With Cholelithiasis Undergoing Cholecystectomy","Abstract":"Gallbladder carcinoma is a lethal disease for its aggressiveness and advanced stage at presentation. Early detection of gallbladder carcinoma is very difficult because of its nonspecific symptoms. Stone and chronic inflammation are important risk factors. But, the exact picture of frequency of gallbladder carcinoma, detected in cholecystectomy specimen in patients with chronic cholecystitis with cholelithiasis, is not clear or unknown. Early diagnosis and prompt surgery for gallstone disease may allow discovery of this deadly disease at an earlier stage where simple cholecystectomy is the curative treatment. To determine the frequency of gallbladder carcinoma in patients undergoing cholecystectomy for cholelithiasis and evaluation of sociodemographic and behavioral risk factors. Two hundred and forty consecutive patients with chronic cholecystitis due to cholelithiasis admitted for cholecystectomy in the Dept. of Surgery, North Bengal Medical College, Darjeeling, during the period from February 2011 to January 2012 were included in the study. Detailed history, examination findings and histopathology reports were noted. Cases of histopathologically-confirmed carcinoma gallbladders were evaluated with descriptive statistics. Out of 240 patients undergoing cholecystectomy, 185 (77.1%) were females and 55 (22.9%) were males. Highest incidence of chronic cholecystitis with cholelithiasis were in the 34-43 years age group (29.2%). Multiple stones were found in 91.3% of cases and the duration of the disease in most patients was 2-4 years. Five patients out of 240 had incidental gallbladder carcinoma. 4 out of 5 gallbladder carcinoma patients had duration of gallstone disease more than 10 years and were in pT1 stage. Prompt cholecystectomy for symptomatic gallstone disease patients should be effective for secondary prevention, detection and treatment of gallbladder carcinoma at an early treatable stage.","Source":"Google Scholar","category":"HUMAN","training_data":"Prevalence Of Gallbladder Carcinoma Among The Patients Of Chronic Cholecystitis With Cholelithiasis Undergoing Cholecystectomy Gallbladder carcinoma is a lethal disease for its aggressiveness and advanced stage at presentation. Early detection of gallbladder carcinoma is very difficult because of its nonspecific symptoms. Stone and chronic inflammation are important risk factors. But, the exact picture of frequency of gallbladder carcinoma, detected in cholecystectomy specimen in patients with chronic cholecystitis with cholelithiasis, is not clear or unknown. Early diagnosis and prompt surgery for gallstone disease may allow discovery of this deadly disease at an earlier stage where simple cholecystectomy is the curative treatment. To determine the frequency of gallbladder carcinoma in patients undergoing cholecystectomy for cholelithiasis and evaluation of sociodemographic and behavioral risk factors. Two hundred and forty consecutive patients with chronic cholecystitis due to cholelithiasis admitted for cholecystectomy in the Dept. of Surgery, North Bengal Medical College, Darjeeling, during the period from February 2011 to January 2012 were included in the study. Detailed history, examination findings and histopathology reports were noted. Cases of histopathologically-confirmed carcinoma gallbladders were evaluated with descriptive statistics. Out of 240 patients undergoing cholecystectomy, 185 (77.1%) were females and 55 (22.9%) were males. Highest incidence of chronic cholecystitis with cholelithiasis were in the 34-43 years age group (29.2%). Multiple stones were found in 91.3% of cases and the duration of the disease in most patients was 2-4 years. Five patients out of 240 had incidental gallbladder carcinoma. 4 out of 5 gallbladder carcinoma patients had duration of gallstone disease more than 10 years and were in pT1 stage. Prompt cholecystectomy for symptomatic gallstone disease patients should be effective for secondary prevention, detection and treatment of gallbladder carcinoma at an early treatable stage. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder carcinoma igc ten years experience introduction gallbladder carcinoma rare high lethal neoplasm suspected preoperatively 30 patients 70 incidentally found histological examination role radical resection disease still debated little known long term survival different recommendation often drawn based small groups data aim study report experience igc evaluate survival outcomes prognosis methods paper offers retrospective descriptive analyses 16 cases igc 4118 cholecystectomies performed january 2000 november 2009 hpb unit according rigorous de nition igcs discovered rst pathologist pre intraoperative suspicion gallbladder cancer exclusion criteria oncological follow updated phone call interviews outpatient visits results total 4118 cholecystectomy 2975 laparoscopic 1143 open igc recognized 16 patients 0 39 13 females 3 males mean age 66 5 ys 43 89 ys following pathological stage according american joint committee cancer ajcc 4 patients t1a cancer 5 patients t1b 4 patients t2 3 patients t3 histological grade equally represented well differentiated g1 6 cases moderately differentiated g2 4 cases poorly differentiated g3 6 cases radical surgery hepatic resection lymphadenectomy performed 5 patients 1 t1b patient 3 t2 1 t3 patients present 7 patients still alive 2 dropped follow conclusion igc presented low incidence 0 39 ten years experience high mortality behaviour homogeneous recommending t2 t3 patients extended resection hepatic gallbladder bed regional lymphadenectomy although small number patients analysed register among 5 still alive disease free patient 3 t2 patients 60 1 t3 prospective studies useful improve knowledge igc google scholar","probabilities":0.9799733,"Title":"Incidental Gallbladder Carcinoma (Igc): Our Ten Years Experience","Abstract":"Introduction: Gallbladder carcinoma is a rare but high lethal neoplasm; it’s suspected preoperatively in 30% of patients, but 70% are incidentally found at the histological examination. The role of radical resection for this disease is still debated and little is known about the long-term survival. Different recommendation are often drawn based on small groups data. The aim of this study was to report our experience with IGC and evaluate survival outcomes and prognosis. Methods: This paper offers a retrospective descriptive analyses of 16 cases of IGC out of 4118 cholecystectomies performed between January 2000 and November 2009 in our HPB Unit, according to the most rigorous defi nition where IGCs were discovered fi rst by the pathologist; pre- and intraoperative suspicion of gallbladder cancer, was a exclusion criteria. Oncological follow up was updated through phone call interviews and outpatient visits. Results: On a total of 4118 cholecystectomy (2975 laparoscopic and 1143 open), IGC was recognized in 16 patients (0.39%), 13 females and 3 males, mean age 66.5 ys (43–89 ys) with the following pathological stage, according to the American Joint Committee on Cancer (AJCC): 4 patients had T1a cancer, 5 patients T1b, 4 patients T2 and 3 patients T3; histological grade was equally represented: well differentiated (G1): 6 cases, moderately differentiated (G2): 4 cases, poorly differentiated (G3): 6 cases. Radical surgery (hepatic resection and lymphadenectomy) was performed in 5 patients: 1 T1b patient, 3 T2 and 1 T3 patients. At present 7 patients are still alive and 2 dropped out the follow up. Conclusion: IGC presented a low incidence (0.39%) in our ten-years experience, with high mortality. Our behaviour was homogeneous in recommending for T2 and T3 patients extended resection of hepatic gallbladder bed and regional lymphadenectomy. Although the small number of patients analysed we can register as among the 5 still alive and disease free patient, 3 were T2 patients (60%) and 1 T3. Prospective studies should be useful to improve our knowledge about IGC.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidental Gallbladder Carcinoma (Igc): Our Ten Years Experience Introduction: Gallbladder carcinoma is a rare but high lethal neoplasm; it’s suspected preoperatively in 30% of patients, but 70% are incidentally found at the histological examination. The role of radical resection for this disease is still debated and little is known about the long-term survival. Different recommendation are often drawn based on small groups data. The aim of this study was to report our experience with IGC and evaluate survival outcomes and prognosis. Methods: This paper offers a retrospective descriptive analyses of 16 cases of IGC out of 4118 cholecystectomies performed between January 2000 and November 2009 in our HPB Unit, according to the most rigorous defi nition where IGCs were discovered fi rst by the pathologist; pre- and intraoperative suspicion of gallbladder cancer, was a exclusion criteria. Oncological follow up was updated through phone call interviews and outpatient visits. Results: On a total of 4118 cholecystectomy (2975 laparoscopic and 1143 open), IGC was recognized in 16 patients (0.39%), 13 females and 3 males, mean age 66.5 ys (43–89 ys) with the following pathological stage, according to the American Joint Committee on Cancer (AJCC): 4 patients had T1a cancer, 5 patients T1b, 4 patients T2 and 3 patients T3; histological grade was equally represented: well differentiated (G1): 6 cases, moderately differentiated (G2): 4 cases, poorly differentiated (G3): 6 cases. Radical surgery (hepatic resection and lymphadenectomy) was performed in 5 patients: 1 T1b patient, 3 T2 and 1 T3 patients. At present 7 patients are still alive and 2 dropped out the follow up. Conclusion: IGC presented a low incidence (0.39%) in our ten-years experience, with high mortality. Our behaviour was homogeneous in recommending for T2 and T3 patients extended resection of hepatic gallbladder bed and regional lymphadenectomy. Although the small number of patients analysed we can register as among the 5 still alive and disease free patient, 3 were T2 patients (60%) and 1 T3. Prospective studies should be useful to improve our knowledge about IGC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"defining unmet need primary sclerosing cholangitis international psc group risk stratification study introduction primary sclerosing cholangitis psc relatively uncommon hepatobiliary disorder associated inflammatory bowel disease ibd wherein therapy transplantation remains ineffective understand disease course within goal appropriately stratified care international psc study group describes natural history clinical phenotypes across largest cohort ever assembled methods collected individual patient data 1980 2010 37 centres 17 countries conducted risk assessment commonly recognised phenotypic associations results 7 119 patients 2 622 progressed liver transplantation death ltd median 14 2 years 722 developed hepatobiliary malignancy incidence rates 47 5 13 7 per 1 000 patient years respectively cholangiocarcinoma frequent malignancy n 596 38 1 cases identified within 1 year psc diagnosis observing patient cohort entirety majority men 65 5 classical large duct disease 89 5 developed ibd point 70 0 ibd consistent crohn disease vs ulcerative colitis absence ibd time conferred lower risk ltd time dependent unadjusted hazard ratio hr 0 61 p 0 001 hr 0 90 p 0 03 respectively malignancy unadj hr 0 68 p 0 007 hr 0 77 p 0 003 respectively small duct psc sdpsc unadj hr 0 50 p 0 001 hr 0 40 p 0 001 ltd malignancy respectively female sex unadj hr 0 89 p 0 018 hr 0 70 p 0 001 ltd malignancy respectively multivariable analyses assessing ltd impact sdpsc classical psc persisted greater protection apparent men adjusted hr 0 31 p 0 001 women adj hr 0 56 p 0 009 however women classical psc expressed lower independent risk disease progression men matched psc subtype adj hr 0 9 p 0 022 ibd phenotype retained independent stratification properties ltd crohn disease ibd absence characterising lower risk subgroups time dependent adj hr 0 69 hr 0 89 p 0 001 p 0 012 respectively sdpsc adj hr 0 45 p 0 02 crohn disease time dependent adj hr 0 72 p 0 045 ibd absence time dependent adj hr 0 72 p 0 02 also independently predictive lower hpb malignancy risk conclusion using robust internationally representative cohort unique size demonstrate distinct clinically meaningful phenotypes stratify outcomes psc highlight great unmet need patients provide risk markers clinically relevant patient care future trial design google scholar","probabilities":0.9799733,"Title":"Defining The Unmet Need In Primary Sclerosing Cholangitis: The International Psc Group Risk Stratification Study","Abstract":"Introduction Primary sclerosing cholangitis (PSC) is a relatively uncommon hepatobiliary disorder associated with inflammatory bowel disease (IBD), wherein therapy other than transplantation remains ineffective. To understand disease course, within a goal of appropriately stratified care, the International PSC Study Group describes the natural history and clinical phenotypes across the largest cohort ever assembled.\nMethods We collected individual-patient data from 1980 to 2010 (37 centres, 17 countries) and conducted risk-assessment for commonly recognised phenotypic associations.\nResults Of 7,119 patients, 2,622 progressed to liver transplantation/death (LTD) (median 14·2 years) and 722 developed hepatobiliary malignancy (incidence rates: 47·5 and 13·7 per-1,000-patient-years, respectively). Cholangiocarcinoma was the most frequent malignancy (n = 596), with 38·1% of cases identified within 1 year of PSC diagnosis. Observing the patient cohort in entirety, the majority were men (65·5%), had classical/large-duct disease (89·5%), and developed IBD at some point (70·0%).\nIBD consistent with Crohn’s disease (vs. ulcerative colitis) or an absence of IBD over time conferred a lower risk of LTD (time-dependent, unadjusted hazard ratio (HR): 0·61, p < 0.001; and HR:0·90, p = 0·03; respectively) and malignancy (unadj. HR:0·68, p = 0·007 and HR:0·77, p = 0·003; respectively), as did small-duct PSC (sdPSC) (unadj. HR:0·50, p < 0·001 and HR:0·40, p < 0·001; for LTD and malignancy, respectively) and female sex (unadj. HR:0·89, p = 0·018 and HR:0·70, p < 0·001; for LTD and malignancy, respectively).\nOn multivariable analyses assessing LTD, the impact of sdPSC over classical PSC persisted, with greater protection apparent for men (adjusted HR:0·31, p < 0·001) than women (adj. HR:0·56, p = 0·009). However, women with classical PSC expressed a lower independent risk of disease progression than men of matched PSC subtype (adj. HR:0·9, p = 0.022). IBD-phenotype retained independent stratification properties of LTD, with Crohn’s disease and IBD-absence characterising lower-risk subgroups (time-dependent adj. HR:0·69 and HR:0·89, p < 0·001 and p = 0.012; respectively). sdPSC (adj. HR:0·45, p = 0·02), Crohn’s disease (time-dependent adj. HR:0·72, p = 0·045), and IBD-absence (time-dependent adj. HR:0·72, p = 0·02) were also independently predictive of a lower HPB malignancy risk.\nConclusion Using a robust, internationally representative cohort of unique size we demonstrate how distinct, clinically meaningful phenotypes stratify outcomes in PSC. We highlight the great-unmet need for patients, and provide risk markers clinically relevant to patient care and future trial design.","Source":"Google Scholar","category":"HUMAN","training_data":"Defining The Unmet Need In Primary Sclerosing Cholangitis: The International Psc Group Risk Stratification Study Introduction Primary sclerosing cholangitis (PSC) is a relatively uncommon hepatobiliary disorder associated with inflammatory bowel disease (IBD), wherein therapy other than transplantation remains ineffective. To understand disease course, within a goal of appropriately stratified care, the International PSC Study Group describes the natural history and clinical phenotypes across the largest cohort ever assembled.\nMethods We collected individual-patient data from 1980 to 2010 (37 centres, 17 countries) and conducted risk-assessment for commonly recognised phenotypic associations.\nResults Of 7,119 patients, 2,622 progressed to liver transplantation/death (LTD) (median 14·2 years) and 722 developed hepatobiliary malignancy (incidence rates: 47·5 and 13·7 per-1,000-patient-years, respectively). Cholangiocarcinoma was the most frequent malignancy (n = 596), with 38·1% of cases identified within 1 year of PSC diagnosis. Observing the patient cohort in entirety, the majority were men (65·5%), had classical/large-duct disease (89·5%), and developed IBD at some point (70·0%).\nIBD consistent with Crohn’s disease (vs. ulcerative colitis) or an absence of IBD over time conferred a lower risk of LTD (time-dependent, unadjusted hazard ratio (HR): 0·61, p < 0.001; and HR:0·90, p = 0·03; respectively) and malignancy (unadj. HR:0·68, p = 0·007 and HR:0·77, p = 0·003; respectively), as did small-duct PSC (sdPSC) (unadj. HR:0·50, p < 0·001 and HR:0·40, p < 0·001; for LTD and malignancy, respectively) and female sex (unadj. HR:0·89, p = 0·018 and HR:0·70, p < 0·001; for LTD and malignancy, respectively).\nOn multivariable analyses assessing LTD, the impact of sdPSC over classical PSC persisted, with greater protection apparent for men (adjusted HR:0·31, p < 0·001) than women (adj. HR:0·56, p = 0·009). However, women with classical PSC expressed a lower independent risk of disease progression than men of matched PSC subtype (adj. HR:0·9, p = 0.022). IBD-phenotype retained independent stratification properties of LTD, with Crohn’s disease and IBD-absence characterising lower-risk subgroups (time-dependent adj. HR:0·69 and HR:0·89, p < 0·001 and p = 0.012; respectively). sdPSC (adj. HR:0·45, p = 0·02), Crohn’s disease (time-dependent adj. HR:0·72, p = 0·045), and IBD-absence (time-dependent adj. HR:0·72, p = 0·02) were also independently predictive of a lower HPB malignancy risk.\nConclusion Using a robust, internationally representative cohort of unique size we demonstrate how distinct, clinically meaningful phenotypes stratify outcomes in PSC. We highlight the great-unmet need for patients, and provide risk markers clinically relevant to patient care and future trial design. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"model based alkaline phosphatase gamma glutamyltransferase gallbladder cancer prognosis purpose evaluate prognostic value alkaline phosphatase alp gamma glutamyltransferase ggt gallbladder cancer gbc materials methods serum alp ggt levels clinicopathological parameters retrospectively evaluated 199 gbc patients receiver operating characteristic roc curve analysis performed determine cut values alp ggt associations overall survival assessed multivariate analysis based significant factors prognostic score model established results roc curve analysis alp 210 u l ggt 43 u l considered elevated overall survival patients elevated alp ggt significantly worse patients within normal range multivariate analysis showed elevated alp ggt tumor stage independent prognostic factors giving positive factor score 1 established preoperative prognostic score model varied outcomes significantly distinguished different score groups roc curve analysis simple score showed great superiority compared widely used tnm staging alp ggt alone traditional tumor markers cea afp ca125 ca199 conclusions elevated alp ggt levels risk predictors gbc patients prognostic model provides infomration varied outcomes patients different score groups pubmed","probabilities":0.9799733,"Title":"Model Based on Alkaline Phosphatase and Gamma-Glutamyltransferase for Gallbladder Cancer Prognosis","Abstract":"PURPOSE: To evaluate the prognostic value of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) in gallbladder cancer (GBC). MATERIALS AND METHODS: Serum ALP and GGT levels and clinicopathological parameters were retrospectively evaluated in 199 GBC patients. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values of ALP and GGT. Then, associations with overall survival were assessed by multivariate analysis. Based on the significant factors, a prognostic score model was established. RESULTS: By ROC curve analysis, ALP≥210 U/L and GGT≥43 U/L were considered elevated. Overall survival for patients with elevated ALP and GGT was significantly worse than for patients within the normal range. Multivariate analysis showed that the elevated ALP, GGT and tumor stage were independent prognostic factors. Giving each positive factor a score of 1, we established a preoperative prognostic score model. Varied outcomes would be significantly distinguished by the different score groups. By further ROC curve analysis, the simple score showed great superiority compared with the widely used TNM staging, each of the ALP or GGT alone, or traditional tumor markers such as CEA, AFP, CA125 and CA199. CONCLUSIONS: Elevated ALP and GGT levels were risk predictors in GBC patients. Our prognostic model provides infomration on varied outcomes of patients from different score groups.","Source":"PubMed","category":"HUMAN","training_data":"Model Based on Alkaline Phosphatase and Gamma-Glutamyltransferase for Gallbladder Cancer Prognosis PURPOSE: To evaluate the prognostic value of alkaline phosphatase (ALP) and gamma-glutamyltransferase (GGT) in gallbladder cancer (GBC). MATERIALS AND METHODS: Serum ALP and GGT levels and clinicopathological parameters were retrospectively evaluated in 199 GBC patients. Receiver operating characteristic (ROC) curve analysis was performed to determine the cut-off values of ALP and GGT. Then, associations with overall survival were assessed by multivariate analysis. Based on the significant factors, a prognostic score model was established. RESULTS: By ROC curve analysis, ALP≥210 U/L and GGT≥43 U/L were considered elevated. Overall survival for patients with elevated ALP and GGT was significantly worse than for patients within the normal range. Multivariate analysis showed that the elevated ALP, GGT and tumor stage were independent prognostic factors. Giving each positive factor a score of 1, we established a preoperative prognostic score model. Varied outcomes would be significantly distinguished by the different score groups. By further ROC curve analysis, the simple score showed great superiority compared with the widely used TNM staging, each of the ALP or GGT alone, or traditional tumor markers such as CEA, AFP, CA125 and CA199. CONCLUSIONS: Elevated ALP and GGT levels were risk predictors in GBC patients. Our prognostic model provides infomration on varied outcomes of patients from different score groups. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pharmacologic il 6ra inhibition cholangiocarcinoma promotes cancer cell growth survival biliary tract cancer btc represents malignant tumor biliary tract including cholangiocarcinoma cca carcinoma gallbladder gbc 5 year survival rate 5 18 due late diagnosis rapid disease progression chronic inflammation one main risk factors cca gbc particular il 6 mediator inflammation act membrane bound receptor alpha chain mil 6r il 6 classic signaling via soluble forms sil 6r il 6 trans signaling however little known impact cellular responses il 6 trans signaling btc analyzed primary tumors whole sections tissue microarrays also searched cancer genome atlas database compared non neoplastic non inflamed gallbladder tissue il 6r downregulated gbc correlated patients overall survival furthermore different cca cell lines compounds activation il 6 hyper il 6 inhibition tocilizumab sgp130fc il 6 classic signaling trans signaling used determine effects cellular processes two modes il 6 signaling inhibition il 6 trans signaling sgp130fc reduced cca cell line viability apoptosis whereas migration proliferation increased conclude il 6r expression good prognostic marker gbc blocking il 6 trans signaling activation il 6 classic signaling tumor promoting activity findings warrant exclusion patients gbc malignancies associated bile metabolism il 6r inhibitor therapy stn","probabilities":0.9467213,"Title":"Pharmacologic Il-6Ra Inhibition In Cholangiocarcinoma Promotes Cancer Cell Growth And Survival","Abstract":"Biliary tract cancer (BTC) represents a malignant tumor of the biliary tract including cholangiocarcinoma (CCA) and the carcinoma of the gallbladder (GBC) with a 5-year survival rate between 5 and 18% due to late diagnosis and rapid disease progression. Chronic inflammation is one of the main risk factors for CCA and GBC in particular. IL-6, as a mediator of inflammation, can act through a membrane-bound receptor alpha-chain (mIL-6R, \"IL-6 classic signaling\") or via soluble forms (sIL-6R, \"IL-6 trans-signaling\"). However, little is known about the impact on cellular responses of IL-6 trans-signaling on BTC. We analyzed primary tumors as whole sections and as tissue microarrays, and also searched The Cancer Genome Atlas database. Compared to non-neoplastic, non-inflamed gallbladder tissue, IL-6Rα was downregulated in GBC, and this correlated with the patients' overall survival. Furthermore, different CCA cell lines and compounds for activation (IL-6 and Hyper-IL-6) or inhibition (Tocilizumab and sgp130Fc) of IL-6 classic signaling and trans-signaling were used to determine their effects on cellular processes between the two modes of IL-6 signaling. Inhibition of IL-6 trans-signaling by sgp130Fc reduced CCA cell line viability and apoptosis, whereas migration and proliferation were increased. We conclude that IL-6Rα expression is a good prognostic marker for GBC, and that the blocking of IL-6 trans-signaling and activation of IL-6 classic signaling have tumor promoting activity. These findings warrant the exclusion of patients with GBC or other malignancies associated with bile metabolism from IL-6R inhibitor therapy.","Source":"STN","category":"HUMAN","training_data":"Pharmacologic Il-6Ra Inhibition In Cholangiocarcinoma Promotes Cancer Cell Growth And Survival Biliary tract cancer (BTC) represents a malignant tumor of the biliary tract including cholangiocarcinoma (CCA) and the carcinoma of the gallbladder (GBC) with a 5-year survival rate between 5 and 18% due to late diagnosis and rapid disease progression. Chronic inflammation is one of the main risk factors for CCA and GBC in particular. IL-6, as a mediator of inflammation, can act through a membrane-bound receptor alpha-chain (mIL-6R, \"IL-6 classic signaling\") or via soluble forms (sIL-6R, \"IL-6 trans-signaling\"). However, little is known about the impact on cellular responses of IL-6 trans-signaling on BTC. We analyzed primary tumors as whole sections and as tissue microarrays, and also searched The Cancer Genome Atlas database. Compared to non-neoplastic, non-inflamed gallbladder tissue, IL-6Rα was downregulated in GBC, and this correlated with the patients' overall survival. Furthermore, different CCA cell lines and compounds for activation (IL-6 and Hyper-IL-6) or inhibition (Tocilizumab and sgp130Fc) of IL-6 classic signaling and trans-signaling were used to determine their effects on cellular processes between the two modes of IL-6 signaling. Inhibition of IL-6 trans-signaling by sgp130Fc reduced CCA cell line viability and apoptosis, whereas migration and proliferation were increased. We conclude that IL-6Rα expression is a good prognostic marker for GBC, and that the blocking of IL-6 trans-signaling and activation of IL-6 classic signaling have tumor promoting activity. These findings warrant the exclusion of patients with GBC or other malignancies associated with bile metabolism from IL-6R inhibitor therapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"overexpression interleukin 35 intrahepatic cholangiocarcinoma prognostic indicator curative resection interleukin 35 il 35 implicated tumorigenesis exact impact intrahepatic cholangiocarcinoma icc clear aim present study explore specific effect il 35 patient prognosis additionally formulated effective prognostic nomogram icc patients curative resection immunohistochemistry applied explore il 35 expression well il 35 receptor il 35r 102 icc patients results showed il 35 highly expressed icc tumor tissues positively associated lymph node metastasis lnm tnm stage vascular invasion independent prognostic factor patients overall survival os recurrence free survival rfs high expression il 35r gp130 il 12r 2 also observed icc cancer tissues gp130 independent prognostic factor os rfs indispensable il 35 mediated icc clinical prognosis nomogram comprising carcinoembryonic antigen lnm il 35 gp130 expression achieved better predictive accuracy compared tnm stage os data support high il 35 expression correlates icc aggressiveness emerges valuable biomarker evaluating icc progression prognosis clinical work pubmed","probabilities":0.88235295,"Title":"Overexpression of interleukin-35 in intrahepatic cholangiocarcinoma is a prognostic indicator after curative resection","Abstract":"Interleukin-35 (IL-35) is implicated in tumorigenesis, but its exact impact on intrahepatic cholangiocarcinoma (ICC) is not clear. The aim of the present study was to explore the specific effect of IL-35 on patient prognosis. Additionally, we formulated an effective prognostic nomogram for ICC patients after curative resection. Immunohistochemistry was applied to explore IL-35 expression as well as IL-35 receptor (IL-35R) in 102 ICC patients. Results showed that IL-35 was highly expressed in ICC tumor tissues and was positively associated with lymph node metastasis (LNM), TNM stage and vascular invasion and was an independent prognostic factor for patients' overall survival (OS) and recurrence-free survival (RFS). High expression of IL-35R (gp130 and IL-12Rβ2) was also observed in ICC cancer tissues, but only gp130 was an independent prognostic factor for OS and RFS and was indispensable in IL-35-mediated ICC clinical prognosis. The nomogram comprising carcinoembryonic antigen, LNM, IL-35 and gp130 expression achieved better predictive accuracy compared with TNM stage for OS. Our data support that high IL-35 expression correlates with ICC aggressiveness and emerges as a valuable biomarker for evaluating ICC progression and prognosis in clinical work.","Source":"PubMed","category":"HUMAN","training_data":"Overexpression of interleukin-35 in intrahepatic cholangiocarcinoma is a prognostic indicator after curative resection Interleukin-35 (IL-35) is implicated in tumorigenesis, but its exact impact on intrahepatic cholangiocarcinoma (ICC) is not clear. The aim of the present study was to explore the specific effect of IL-35 on patient prognosis. Additionally, we formulated an effective prognostic nomogram for ICC patients after curative resection. Immunohistochemistry was applied to explore IL-35 expression as well as IL-35 receptor (IL-35R) in 102 ICC patients. Results showed that IL-35 was highly expressed in ICC tumor tissues and was positively associated with lymph node metastasis (LNM), TNM stage and vascular invasion and was an independent prognostic factor for patients' overall survival (OS) and recurrence-free survival (RFS). High expression of IL-35R (gp130 and IL-12Rβ2) was also observed in ICC cancer tissues, but only gp130 was an independent prognostic factor for OS and RFS and was indispensable in IL-35-mediated ICC clinical prognosis. The nomogram comprising carcinoembryonic antigen, LNM, IL-35 and gp130 expression achieved better predictive accuracy compared with TNM stage for OS. Our data support that high IL-35 expression correlates with ICC aggressiveness and emerges as a valuable biomarker for evaluating ICC progression and prognosis in clinical work. PubMed","prediction_labels":"HUMAN"},{"cleaned":"characterization prognostic significance mortalin bcl 2 bax intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc aggressive type cancer incidence mortality rates increasing worldwide mortalin highly conserved chaperone protein involved multiple pathological physiological processes including anti apoptosis carcinogenesis metastasis bcl 2 family proteins divided pro survival pro apoptotic members including b cell lymphoma 2 bcl 2 bcl 2 like protein 4 bax aim present study investigate association mortalin bcl 2 bax well prognostic significance combined expression mortalin bcl 2 bax icc immunohistochemistry used determine expression mortalin bcl 2 bax 116 icc samples assess association expression 3 markers clinicopathological features icc patients revealed icc tumor tissues overexpressed mortalin bcl 2 exhibited low expression bax icc tumor tissues compared corresponding peritumoral samples according pearson correlation coefficient analysis high expression mortalin icc positively correlated bcl 2 expression negatively correlated bax expression furthermore multiple linear regression analysis demonstrated mortalin positively associated bcl 2 bax patients icc patients icc exhibiting high expression mortalin bcl 2 low expression bax closely associated malignant icc phenotype relatively low overall survival rate high recurrence rate multivariate analysis indicated mortalin bcl 2 independent prognostic indicators icc patients meanwhile concomitant overexpression mortalin bcl 2 low expression bax independent markers predicting relatively poor prognosis icc overexpression mortalin bcl 2 low expression bax implicated anti apoptotic effect tumor progression icc mortalin bcl 2 combination mortalin bcl 2 bax may used predict prognosis icc well potential therapeutic targets stn","probabilities":0.54545456,"Title":"Characterization And Prognostic Significance Of Mortalin Bcl-2 And Bax In Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is an aggressive type of cancer, and its incidence and mortality rates are increasing worldwide. Mortalin is a highly conserved chaperone protein involved in multiple pathological and physiological processes, including anti-apoptosis, carcinogenesis and metastasis. The Bcl-2 family of proteins can be divided into pro-survival and pro-apoptotic members, including B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax). The aim of the present study was to investigate the association between mortalin, Bcl-2 and Bax, as well as the prognostic significance of the combined expression of mortalin, Bcl-2 and Bax in ICC. Immunohistochemistry was used to determine the expression of mortalin, Bcl-2 and Bax in 116 ICC samples and to assess the association between expression of 3 markers and clinicopathological features of ICC patients. This revealed that ICC tumor tissues overexpressed mortalin and Bcl-2 and exhibited low expression of Bax in ICC tumor tissues compared with that in corresponding peritumoral samples. According to Pearson's correlation coefficient analysis, high expression of mortalin in ICC was positively correlated with Bcl-2 expression and negatively correlated with Bax expression. Furthermore, multiple linear regression analysis demonstrated that mortalin was positively associated with Bcl-2, but not with Bax, in patients with ICC. Patients with ICC exhibiting high expression of mortalin/Bcl-2 or low expression of Bax were closely associated with a malignant ICC phenotype, a relatively low overall survival rate and a high recurrence rate. Multivariate analysis indicated that mortalin and Bcl-2 were independent prognostic indicators for ICC patients. Meanwhile, the concomitant overexpression of mortalin and Bcl-2 and the low expression of Bax were independent markers for predicting a relatively poor prognosis of ICC. The overexpression of mortalin and Bcl-2 and/or the low expression of Bax are implicated in the anti-apoptotic effect and tumor progression of ICC. Mortalin or Bcl-2, or a combination of mortalin, Bcl-2 and Bax may be used to predict the prognosis of ICC, as well as potential therapeutic targets.","Source":"STN","category":"HUMAN","training_data":"Characterization And Prognostic Significance Of Mortalin Bcl-2 And Bax In Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is an aggressive type of cancer, and its incidence and mortality rates are increasing worldwide. Mortalin is a highly conserved chaperone protein involved in multiple pathological and physiological processes, including anti-apoptosis, carcinogenesis and metastasis. The Bcl-2 family of proteins can be divided into pro-survival and pro-apoptotic members, including B-cell lymphoma 2 (Bcl-2) and Bcl-2-like protein 4 (Bax). The aim of the present study was to investigate the association between mortalin, Bcl-2 and Bax, as well as the prognostic significance of the combined expression of mortalin, Bcl-2 and Bax in ICC. Immunohistochemistry was used to determine the expression of mortalin, Bcl-2 and Bax in 116 ICC samples and to assess the association between expression of 3 markers and clinicopathological features of ICC patients. This revealed that ICC tumor tissues overexpressed mortalin and Bcl-2 and exhibited low expression of Bax in ICC tumor tissues compared with that in corresponding peritumoral samples. According to Pearson's correlation coefficient analysis, high expression of mortalin in ICC was positively correlated with Bcl-2 expression and negatively correlated with Bax expression. Furthermore, multiple linear regression analysis demonstrated that mortalin was positively associated with Bcl-2, but not with Bax, in patients with ICC. Patients with ICC exhibiting high expression of mortalin/Bcl-2 or low expression of Bax were closely associated with a malignant ICC phenotype, a relatively low overall survival rate and a high recurrence rate. Multivariate analysis indicated that mortalin and Bcl-2 were independent prognostic indicators for ICC patients. Meanwhile, the concomitant overexpression of mortalin and Bcl-2 and the low expression of Bax were independent markers for predicting a relatively poor prognosis of ICC. The overexpression of mortalin and Bcl-2 and/or the low expression of Bax are implicated in the anti-apoptotic effect and tumor progression of ICC. Mortalin or Bcl-2, or a combination of mortalin, Bcl-2 and Bax may be used to predict the prognosis of ICC, as well as potential therapeutic targets. STN","prediction_labels":"HUMAN"},{"cleaned":"abcc3 novel prognostic marker cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Abcc3 As A Novel Prognostic Marker In Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Abcc3 As A Novel Prognostic Marker In Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"karnofsky performance score predictive survival palliative irradiation metastatic bile duct cancer background aim palliative irradiation effective alleviating symptoms patients metastatic cancer general however little data exist regarding irradiation metastatic bile duct cancer selection best regimen patient based survival prognosis patients methods study included five patients irradiated metastatic bile duct cancer aimed identify predictors survival analyzing six factors age gender general condition karnofsky performance score metastatic site receiving palliative irradiation metastases outside irradiated sites time diagnosis bile duct cancer palliative irradiation results whole series median survival 3 months survival rates 3 6 months 40 40 respectively karnofsky performance score 70 borderline significant association better survival p 0 05 conclusion karnofsky performance score identified predictor survival considered assigning radiation regimen patients metastatic bile duct cancer stn","probabilities":0.9799733,"Title":"Karnofsky Performance Score Is Predictive Of Survival After Palliative Irradiation Of Metastatic Bile Duct Cancer","Abstract":"Background/aim: Palliative irradiation is effective in alleviating symptoms in patients with metastatic cancer in general. However, little data exist regarding irradiation of metastatic bile duct cancer. Selection of the best regimen for such a patient should be based on their survival prognosis. \r\n\r\n Patients and methods: This study included five patients irradiated for metastatic bile duct cancer and aimed to identify predictors of survival by analyzing six factors: age, gender, general condition (Karnofsky performance score), metastatic site receiving palliative irradiation, metastases outside irradiated sites and time between diagnosis of bile duct cancer and palliative irradiation. \r\n\r\n Results: In the whole series, median survival was 3 months. Survival rates at 3 and 6 months were 40% and 40%, respectively. A Karnofsky performance score >70% had a borderline significant association with better survival (p=0.05). \r\n\r\n Conclusion: Karnofsky performance score was identified as predictor of survival and should be considered when assigning the radiation regimen to patients with metastatic bile duct cancer.","Source":"STN","category":"HUMAN","training_data":"Karnofsky Performance Score Is Predictive Of Survival After Palliative Irradiation Of Metastatic Bile Duct Cancer Background/aim: Palliative irradiation is effective in alleviating symptoms in patients with metastatic cancer in general. However, little data exist regarding irradiation of metastatic bile duct cancer. Selection of the best regimen for such a patient should be based on their survival prognosis. \r\n\r\n Patients and methods: This study included five patients irradiated for metastatic bile duct cancer and aimed to identify predictors of survival by analyzing six factors: age, gender, general condition (Karnofsky performance score), metastatic site receiving palliative irradiation, metastases outside irradiated sites and time between diagnosis of bile duct cancer and palliative irradiation. \r\n\r\n Results: In the whole series, median survival was 3 months. Survival rates at 3 and 6 months were 40% and 40%, respectively. A Karnofsky performance score >70% had a borderline significant association with better survival (p=0.05). \r\n\r\n Conclusion: Karnofsky performance score was identified as predictor of survival and should be considered when assigning the radiation regimen to patients with metastatic bile duct cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"primary sclerosing cholangitis gastroenterologist hepatologist needs know primary sclerosing cholangitis psc chronic idiopathic biliary tract disease characterized segmental strictures disease progressive proven treatments may eventually lead cirrhosis end stage liver disease abrupt changes liver biochemistries pain cholangitis may suggest dominant stricture amenable endoscopic therapy development cholangiocarcinoma patients psc increased risk cholangiocarcinoma strong association inflammatory bowel disease associated increased risk colorectal cancer colonoscopy every 1 2 years appropriate pubmed","probabilities":0.9799733,"Title":"Primary Sclerosing Cholangitis: What the Gastroenterologist and Hepatologist Needs to Know","Abstract":"Primary sclerosing cholangitis (PSC) is a chronic, idiopathic biliary tract disease characterized by segmental strictures. The disease is progressive with no proven treatments and may eventually lead to cirrhosis and end-stage liver disease. Abrupt changes in liver biochemistries, pain, and/or cholangitis may suggest a dominant stricture amenable to endoscopic therapy or the development of cholangiocarcinoma. Patients with PSC are at increased risk of cholangiocarcinoma. There is a strong association with inflammatory bowel disease, and an associated increased risk of colorectal cancer. Colonoscopy every 1 to 2 years is appropriate.","Source":"PubMed","category":"HUMAN","training_data":"Primary Sclerosing Cholangitis: What the Gastroenterologist and Hepatologist Needs to Know Primary sclerosing cholangitis (PSC) is a chronic, idiopathic biliary tract disease characterized by segmental strictures. The disease is progressive with no proven treatments and may eventually lead to cirrhosis and end-stage liver disease. Abrupt changes in liver biochemistries, pain, and/or cholangitis may suggest a dominant stricture amenable to endoscopic therapy or the development of cholangiocarcinoma. Patients with PSC are at increased risk of cholangiocarcinoma. There is a strong association with inflammatory bowel disease, and an associated increased risk of colorectal cancer. Colonoscopy every 1 to 2 years is appropriate. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term survival resection perihilar cholangiocarcinoma impact uicc staging surgical procedure background aims perihilar cholangiocarcinoma rare disease unfavorable prognosis resulting low survival rates study aims retrospectively assess beneficial histopathological features surgical procedures long term survivors e patients surviving perihilar cholangiocarcinoma least 2 y material methods total 322 patients perihilar cholangiocarcinoma underwent surgery center follow ended 2017 76 patients survived 2 y type resection uicc stage histopathological features compared three survival groups 2 3 3 5 5 y results 5 year survival rate selected study cohort 43 4 3 5 y 31 6 2 3 y 25 0 14 5 patients survived 10 y surgery patients non regional lymph node positive tumors distant metastasis e uicc stage ivb p 0 0112 r2 status p 0 0288 exploratory laparotomy p 0 0157 showed poorest survival rates perineural invasion significant impact overall survival however 29 0 patients surviving 5 y displayed lowest perineural infiltration prevalence interestingly bismuth corlette stage iiia p 0 0467 especially caudate lobectomy p 0 0034 associated disease specific overall survival 5y conclusion complete extended tumor resection additional caudate lobe resection strongly associated long term survival perineural infiltration negative prognostic marker prolonged survival needs evaluated larger study cohorts pubmed","probabilities":0.9799733,"Title":"Long-term Survival after resection for perihilar cholangiocarcinoma: Impact of UICC staging and surgical procedure","Abstract":"BACKGROUND/AIMS: Perihilar cholangiocarcinoma is a rare disease with unfavorable prognosis resulting in low survival rates. This study aims to retrospectively assess the beneficial histopathological features and surgical procedures in long-term survivors (i.e., patients surviving perihilar cholangiocarcinoma for at least 2 y). MATERIAL AND METHODS: In total, 322 patients with perihilar cholangiocarcinoma underwent surgery at our center. The follow-up ended in 2017; 76 patients survived for >2 y. The type of resection, UICC stage, and histopathological features were compared between three survival groups (>2-3, >3-5, and >5 y). RESULTS: The >5-year-survival rate in our selected study cohort was 43.4% (>3-5 y,31.6% and >2-3 y, 25.0%), and 14.5% of the patients survived for >10 y after surgery. Patients with non-regional lymph node positive tumors and/or distant metastasis (i.e., UICC stage IVb; p=0.0112), R2 status (p=0.0288), and exploratory laparotomy only (p=0.0157) showed the poorest survival rates. Perineural invasion had no significant impact on the overall survival. However, 29.0% patients surviving for >5 y displayed the lowest perineural infiltration prevalence. Interestingly, Bismuth-Corlette stage IIIa (p=0.0467), especially caudate lobectomy (p=0.0034), was associated with disease-specific overall survival of >5y. CONCLUSION: Complete/extended tumor resection with additional caudate lobe resection is strongly associated with long-term survival. Perineural infiltration as a negative prognostic marker for prolonged survival needs to be evaluated in larger study cohorts.","Source":"PubMed","category":"HUMAN","training_data":"Long-term Survival after resection for perihilar cholangiocarcinoma: Impact of UICC staging and surgical procedure BACKGROUND/AIMS: Perihilar cholangiocarcinoma is a rare disease with unfavorable prognosis resulting in low survival rates. This study aims to retrospectively assess the beneficial histopathological features and surgical procedures in long-term survivors (i.e., patients surviving perihilar cholangiocarcinoma for at least 2 y). MATERIAL AND METHODS: In total, 322 patients with perihilar cholangiocarcinoma underwent surgery at our center. The follow-up ended in 2017; 76 patients survived for >2 y. The type of resection, UICC stage, and histopathological features were compared between three survival groups (>2-3, >3-5, and >5 y). RESULTS: The >5-year-survival rate in our selected study cohort was 43.4% (>3-5 y,31.6% and >2-3 y, 25.0%), and 14.5% of the patients survived for >10 y after surgery. Patients with non-regional lymph node positive tumors and/or distant metastasis (i.e., UICC stage IVb; p=0.0112), R2 status (p=0.0288), and exploratory laparotomy only (p=0.0157) showed the poorest survival rates. Perineural invasion had no significant impact on the overall survival. However, 29.0% patients surviving for >5 y displayed the lowest perineural infiltration prevalence. Interestingly, Bismuth-Corlette stage IIIa (p=0.0467), especially caudate lobectomy (p=0.0034), was associated with disease-specific overall survival of >5y. CONCLUSION: Complete/extended tumor resection with additional caudate lobe resection is strongly associated with long-term survival. Perineural infiltration as a negative prognostic marker for prolonged survival needs to be evaluated in larger study cohorts. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hospital mortality resection biliary tract cancer united states objective assess perioperative mortality following resection biliary tract cancer within u background resection remains curative treatment biliary tract cancer however current data operative mortality surgical resections biliary tract cancer limited small single center studies methods using nationwide inpatient sample 1998 2006 cohort patient discharges assembled diagnosis biliary tract cancer including intrahepatic bile duct extrahepatic bile duct gall bladder cancers patients undergoing resection including hepatic resection bile duct resection pancreaticoduodenectomy cholecystectomy retained primary outcome measure hospital mortality categorical variables analyzed chi square multivariable logistic regression performed identify independent predictors hospital mortality following resection results 31 870 patient discharges occurred diagnosis biliary tract cancer including 36 2 intrahepatic ductal 26 7 extrahepatic ductal 31 1 gall bladder total 18 6 underwent resection mean age 69 3 years median 70 0 60 8 female 73 7 white overall inpatient surgical mortality 5 6 independently predictive factors mortality included patient age 50 vs 50 age 50 59 odds ratio 5 51 95 confidence interval ci 1 70 17 93 age 60 69 7 25 95 ci 2 29 22 96 age 70 9 03 95 ci 2 86 28 56 presence identified comorbidities congestive heart failure 3 67 95 ci 2 61 5 16 renal failure 4 72 95 ci 2 97 7 49 admission designated emergent vs elective 1 82 95 ci 1 39 2 37 conclusion increased hospital mortality patients undergoing biliary tract cancer resection corresponded age comorbidity hospital volume emergent admission study warranted utilize observations promoting early detection diagnosis elective resection google scholar","probabilities":0.9799733,"Title":"In-Hospital Mortality After Resection Of Biliary Tract Cancer In The United States","Abstract":"Objective\nTo assess perioperative mortality following resection of biliary tract cancer within the U.S.\nBackground\nResection remains the only curative treatment for biliary tract cancer. However, current data on operative mortality after surgical resections for biliary tract cancer are limited to small and single-center studies.\nMethods\nUsing the Nationwide Inpatient Sample 1998–2006, a cohort of patient-discharges was assembled with a diagnosis of biliary tract cancer, including intrahepatic bile duct, extrahepatic bile duct, and gall bladder cancers. Patients undergoing resection, including hepatic resection, bile duct resection, pancreaticoduodenectomy, and cholecystectomy, were retained. The primary outcome measure was in-hospital mortality. Categorical variables were analyzed by chi-square. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality following resection.\nResults\n31 870 patient-discharges occurred for the diagnosis of biliary tract cancer, including 36.2% intrahepatic ductal, 26.7% extrahepatic ductal, and 31.1% gall bladder. Of the total, 18.6% underwent resection: mean age was 69.3 years (median 70.0); 60.8% were female; 73.7% were white. Overall inpatient surgical mortality was 5.6%. Independently predictive factors of mortality included patient age ≥50 (vs. <50; age 50–59 odds ratio [OR] 5.51, 95% confidence interval [CI] 1.70–17.93; age 60–69 OR 7.25, 95% CI 2.29–22.96; age ≥ 70 OR 9.03, 95% CI 2.86–28.56), the presence of identified comorbidities (congestive heart failure, OR 3.67, 95% CI 2.61–5.16; renal failure, OR 4.72, 95% CI 2.97–7.49), and admission designated as emergent (vs. elective; OR 1.82, 95% CI 1.39–2.37).\nConclusion\nIncreased in-hospital mortality for patients undergoing biliary tract cancer resection corresponded to age, comorbidity, hospital volume, and emergent admission. Further study is warranted to utilize these observations in promoting early detection, diagnosis, and elective resection.","Source":"Google Scholar","category":"HUMAN","training_data":"In-Hospital Mortality After Resection Of Biliary Tract Cancer In The United States Objective\nTo assess perioperative mortality following resection of biliary tract cancer within the U.S.\nBackground\nResection remains the only curative treatment for biliary tract cancer. However, current data on operative mortality after surgical resections for biliary tract cancer are limited to small and single-center studies.\nMethods\nUsing the Nationwide Inpatient Sample 1998–2006, a cohort of patient-discharges was assembled with a diagnosis of biliary tract cancer, including intrahepatic bile duct, extrahepatic bile duct, and gall bladder cancers. Patients undergoing resection, including hepatic resection, bile duct resection, pancreaticoduodenectomy, and cholecystectomy, were retained. The primary outcome measure was in-hospital mortality. Categorical variables were analyzed by chi-square. Multivariable logistic regression was performed to identify independent predictors of in-hospital mortality following resection.\nResults\n31 870 patient-discharges occurred for the diagnosis of biliary tract cancer, including 36.2% intrahepatic ductal, 26.7% extrahepatic ductal, and 31.1% gall bladder. Of the total, 18.6% underwent resection: mean age was 69.3 years (median 70.0); 60.8% were female; 73.7% were white. Overall inpatient surgical mortality was 5.6%. Independently predictive factors of mortality included patient age ≥50 (vs. <50; age 50–59 odds ratio [OR] 5.51, 95% confidence interval [CI] 1.70–17.93; age 60–69 OR 7.25, 95% CI 2.29–22.96; age ≥ 70 OR 9.03, 95% CI 2.86–28.56), the presence of identified comorbidities (congestive heart failure, OR 3.67, 95% CI 2.61–5.16; renal failure, OR 4.72, 95% CI 2.97–7.49), and admission designated as emergent (vs. elective; OR 1.82, 95% CI 1.39–2.37).\nConclusion\nIncreased in-hospital mortality for patients undergoing biliary tract cancer resection corresponded to age, comorbidity, hospital volume, and emergent admission. Further study is warranted to utilize these observations in promoting early detection, diagnosis, and elective resection. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"association cancer stem cell markers genetic variants gallbladder cancer susceptibility prognosis survival genes important stem cell progression involved genetics clinical outcome cancers investigated germ line variants cancer stem cell csc genes predict susceptibility efficacy chemoradiotherapy treatment gallbladder cancer gbc patients study assessed effect snps csc genes surface markers cd44 alcam epcam cd133 molecular markers nanog sox 2 lin 28a aldh1a1 oct 4 gbc susceptibility prognosis total 610 gbc patients 250 controls genotyped using pcr rflp arms pcr taqman allelic discrimination assays chemotoxicity graded 2 4 200 patients tumor response recorded 140 patients undergoing neoadjuvant chemotherapy nact differences genotype haplotype frequency distributions calculated binary logistic regression gene gene interaction model analyzed generalized multifactor dimensionality reduction gmdr overall survival assessed kaplan meier survival curve multivariate cox proportional methods alcam ars1157crs10511244 p 0 0035 haplotype significantly associated gbc susceptibility gmdr analysis alcam rs1157g epcam rs1126497t c emerged best significant interaction model gbc susceptibility aldh1a1 rs13959t g increased risk grade 3 4 hematological toxicity sox 2 rs11915160a c oct 4 rs3130932t g nanog rs11055786t c found best gene gene interaction model predicting response nact cox proportional recursive partitioning alcam rs1157ga aa genotype showed higher mortality hazard ratio alcam gene polymorphisms associated gbc susceptibility survival oct 4 sox 2 nanog variants showed interactive role treatment response pubmed","probabilities":0.962963,"Title":"Association of cancer stem cell markers genetic variants with gallbladder cancer susceptibility, prognosis, and survival","Abstract":"Genes important to stem cell progression have been involved in the genetics and clinical outcome of cancers. We investigated germ line variants in cancer stem cell (CSC) genes to predict susceptibility and efficacy of chemoradiotherapy treatment in gallbladder cancer (GBC) patients. In this study, we assessed the effect of SNPs in CSC genes (surface markers CD44, ALCAM, EpCAM, CD133) and (molecular markers NANOG, SOX-2, LIN-28A, ALDH1A1, OCT-4) with GBC susceptibility and prognosis. Total 610 GBC patients and 250 controls were genotyped by using PCR-RFLP, ARMS-PCR, and TaqMan allelic discrimination assays. Chemotoxicity graded 2-4 in 200 patients and tumor response was recorded in 140 patients undergoing neoadjuvant chemotherapy (NACT). Differences in genotype and haplotype frequency distributions were calculated by binary logistic regression. Gene-gene interaction model was analyzed by generalized multifactor dimensionality reduction (GMDR). Overall survival was assessed by Kaplan-Meier survival curve and multivariate Cox-proportional methods. ALCAM Ars1157Crs10511244 (P = 0.0035) haplotype was significantly associated with GBC susceptibility. In GMDR analysis, ALCAM rs1157G>A, EpCAM rs1126497T>C emerged as best significant interaction model with GBC susceptibility and ALDH1A1 rs13959T>G with increased risk of grade 3-4 hematological toxicity. SOX-2 rs11915160A>C, OCT-4 rs3130932T>G, and NANOG rs11055786T>C were found best gene-gene interaction model for predicting response to NACT. In both Cox-proportional and recursive partitioning ALCAM rs1157GA+AA genotype showed higher mortality and hazard ratio. ALCAM gene polymorphisms associated with GBC susceptibility and survival while OCT-4, SOX-2, and NANOG variants showed an interactive role with treatment response.","Source":"PubMed","category":"HUMAN","training_data":"Association of cancer stem cell markers genetic variants with gallbladder cancer susceptibility, prognosis, and survival Genes important to stem cell progression have been involved in the genetics and clinical outcome of cancers. We investigated germ line variants in cancer stem cell (CSC) genes to predict susceptibility and efficacy of chemoradiotherapy treatment in gallbladder cancer (GBC) patients. In this study, we assessed the effect of SNPs in CSC genes (surface markers CD44, ALCAM, EpCAM, CD133) and (molecular markers NANOG, SOX-2, LIN-28A, ALDH1A1, OCT-4) with GBC susceptibility and prognosis. Total 610 GBC patients and 250 controls were genotyped by using PCR-RFLP, ARMS-PCR, and TaqMan allelic discrimination assays. Chemotoxicity graded 2-4 in 200 patients and tumor response was recorded in 140 patients undergoing neoadjuvant chemotherapy (NACT). Differences in genotype and haplotype frequency distributions were calculated by binary logistic regression. Gene-gene interaction model was analyzed by generalized multifactor dimensionality reduction (GMDR). Overall survival was assessed by Kaplan-Meier survival curve and multivariate Cox-proportional methods. ALCAM Ars1157Crs10511244 (P = 0.0035) haplotype was significantly associated with GBC susceptibility. In GMDR analysis, ALCAM rs1157G>A, EpCAM rs1126497T>C emerged as best significant interaction model with GBC susceptibility and ALDH1A1 rs13959T>G with increased risk of grade 3-4 hematological toxicity. SOX-2 rs11915160A>C, OCT-4 rs3130932T>G, and NANOG rs11055786T>C were found best gene-gene interaction model for predicting response to NACT. In both Cox-proportional and recursive partitioning ALCAM rs1157GA+AA genotype showed higher mortality and hazard ratio. ALCAM gene polymorphisms associated with GBC susceptibility and survival while OCT-4, SOX-2, and NANOG variants showed an interactive role with treatment response. PubMed","prediction_labels":"HUMAN"},{"cleaned":"platelet lymphocyte ratio novel prognostic tool gallbladder carcinoma aim preliminarily investigate prognostic significance platelet lymphocyte ratio plr patients gallbladder carcinoma gbc methods clinical data 316 surgical gbc patients analyzed retrospectively preoperative serum platelet lymphocyte counts used calculate plr optimal cut value plr detecting death determined receiver operating characteristic roc curve primary outcome overall survival estimated kaplan meier method log rank test used compare differences survival conducted multivariate cox analysis assess independent effect plr survival gbc patients results plr area roc curve 0 620 95 ci 0 542 0 698 p 0 040 detecting death cut value plr determined 117 7 73 6 sensitivity 53 2 specificity plr found significantly positively correlated ca125 serum level tumor node metastasis tnm stage tumor differentiation univariate analysis identified carcinoembryonic antigen cea ca125 ca199 levels plr tnm stage degree differentiation significant prognostic factors gbc expressed binary data multivariate analysis showed ca125 35 u ml ca199 39 u ml plr 117 7 tnm stage iv independently associated poor survival gbc expressed continuous variable plr still independent predictor survival hazard ratio 1 018 95 ci 1 001 1 037 per 10 unit increase p 0 043 conclusion plr used simple inexpensive valuable tool predicting prognosis gbc patients pubmed","probabilities":0.9799733,"Title":"Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma","Abstract":"AIM: To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio (PLR) in patients with gallbladder carcinoma (GBC). METHODS: Clinical data of 316 surgical GBC patients were analyzed retrospectively, and preoperative serum platelet and lymphocyte counts were used to calculate the PLR. The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic (ROC) curve. The primary outcome was overall survival, which was estimated by the Kaplan-Meier method. The log-rank test was used to compare the differences in survival. Then, we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients. RESULTS: For the PLR, the area under the ROC curve was 0.620 (95%CI: 0.542-0.698, P = 0.040) in detecting death. The cut-off value for the PLR was determined to be 117.7, with 73.6% sensitivity and 53.2% specificity. The PLR was found to be significantly positively correlated with CA125 serum level, tumor-node-metastasis (TNM) stage, and tumor differentiation. Univariate analysis identified carcinoembryonic antigen (CEA), CA125 and CA199 levels, PLR, TNM stage, and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data. Multivariate analysis showed that CA125 > 35 U/mL, CA199 > 39 U/mL, PLR ≥ 117.7, and TNM stage IV were independently associated with poor survival in GBC. When expressed as a continuous variable, the PLR was still an independent predictor for survival, with a hazard ratio of 1.018 (95%CI: 1.001-1.037 per 10-unit increase, P = 0.043). CONCLUSION: The PLR could be used as a simple, inexpensive, and valuable tool for predicting the prognosis of GBC patients.","Source":"PubMed","category":"HUMAN","training_data":"Platelet to lymphocyte ratio as a novel prognostic tool for gallbladder carcinoma AIM: To preliminarily investigate the prognostic significance of the platelet to lymphocyte ratio (PLR) in patients with gallbladder carcinoma (GBC). METHODS: Clinical data of 316 surgical GBC patients were analyzed retrospectively, and preoperative serum platelet and lymphocyte counts were used to calculate the PLR. The optimal cut-off value of the PLR for detecting death was determined by the receiver operating characteristic (ROC) curve. The primary outcome was overall survival, which was estimated by the Kaplan-Meier method. The log-rank test was used to compare the differences in survival. Then, we conducted multivariate Cox analysis to assess the independent effect of the PLR on the survival of GBC patients. RESULTS: For the PLR, the area under the ROC curve was 0.620 (95%CI: 0.542-0.698, P = 0.040) in detecting death. The cut-off value for the PLR was determined to be 117.7, with 73.6% sensitivity and 53.2% specificity. The PLR was found to be significantly positively correlated with CA125 serum level, tumor-node-metastasis (TNM) stage, and tumor differentiation. Univariate analysis identified carcinoembryonic antigen (CEA), CA125 and CA199 levels, PLR, TNM stage, and the degree of differentiation as significant prognostic factors for GBC when they were expressed as binary data. Multivariate analysis showed that CA125 > 35 U/mL, CA199 > 39 U/mL, PLR ≥ 117.7, and TNM stage IV were independently associated with poor survival in GBC. When expressed as a continuous variable, the PLR was still an independent predictor for survival, with a hazard ratio of 1.018 (95%CI: 1.001-1.037 per 10-unit increase, P = 0.043). CONCLUSION: The PLR could be used as a simple, inexpensive, and valuable tool for predicting the prognosis of GBC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radiotherapy chemoradiation unresectable biliary cancer retrospective study background aim retrospectively evaluate outcome patients unresectable biliary cholangiocarcinoma cc treated radiotherapy rt plus minus chemotherapy cht materials methods data patients intrahepatic cc icc klatskin tumor kt distal extrahepatic cc ecc gallbladder cancer gbc diagnosed 1991 2017 retrospectively analyzed treatment mainly based rt plus concurrent cht brachytherapy brt boost kaplan meier method used calculate survival curves compared using log rank test results seventy six patients included analysis males 59 females 41 median age 66 5 years minority patients 7 9 treated disease recurrence surgery according tnm 78 5 patients stage 3 77 6 patients treated concurrent cht rt 22 3 received rt followed sequential cht median rt dose 50 gy range 16 75 gy delivered conventional fractionation cht based gemcitabine 5 fluorouracil brt prescribed 51 3 patient median dose 14 gy reported grade 3 acute gi hematological toxicity 13 2 8 1 respectively severe acute toxicities reported one 2 year overall survival os 58 1 25 8 respectively median 13 5 months 1 2 year progression free survival pfs 43 4 9 4 respectively none following variables significant impact os pfs brt boost tumor site concurrent cht drugs used concurrent cht contrast patients receiving rt 2d technique showed pfs significantly higher compared patients treated 3d technique median 15 5 vs 8 5 months p 0 02 conclusion combined modality treatment rt cht brt unresectable biliary cancer associated acceptable toxicity os comparable actual standard treatment cht significantly improved pfs patients undergoing 2d rt raises doubts regarding adequacy target delineation neoplasms pubmed","probabilities":0.9799733,"Title":"Radiotherapy or Chemoradiation in Unresectable Biliary Cancer: A Retrospective Study","Abstract":"BACKGROUND/AIM: To retrospectively evaluate the outcome of patients with unresectable biliary cholangiocarcinoma (CC) treated with radiotherapy (RT) plus/minus chemotherapy (CHT). MATERIALS AND METHODS: Data of patients with intrahepatic CC (ICC), Klatskin's tumor (KT), distal extrahepatic CC (ECC), and gallbladder cancer (GBC) diagnosed from 1991 to 2017 were retrospectively analyzed. The treatment was mainly based on RT plus concurrent CHT +/- brachytherapy (BRT) boost. The Kaplan-Meier method was used to calculate survival curves that were compared using the log-rank test. RESULTS: Seventy-six patients were included in this analysis (males: 59%; females: 41%; median age: 66.5 years). A minority of patients (7.9%) were treated for disease recurrence after surgery. According to TNM, 78.5% of patients had T stage >3 and 77.6% of patients were treated with concurrent CHT-RT while 22.3% received RT followed by sequential CHT. Median RT dose was 50 Gy (range: 16-75 Gy) delivered with conventional fractionation. CHT was based on Gemcitabine or 5-fluorouracil. BRT was prescribed to 51.3% of patient with a median dose of 14 Gy. Reported Grade ≥3 acute GI and hematological toxicity were 13.2% and 8.1%, respectively. No other severe acute toxicities were reported. One- and 2-year overall survival (OS) were 58.1% and 25.8%, respectively (median: 13.5 months), while 1- and 2-year progression-free survival (PFS) were 43.4% and 9.4%, respectively. None of the following variables had a significant impact on OS and PFS: BRT boost, tumor site, concurrent CHT, and the drugs used in concurrent CHT. In contrast, patients receiving RT with 2D technique showed a PFS significantly higher compared to patients treated with the 3D technique (median: 15.5 vs. 8.5 months; p=0.02). CONCLUSION: Combined modality treatment (RT+CHT±BRT) in unresectable biliary cancer was associated with acceptable toxicity and OS comparable to the actual standard treatment (CHT). The significantly improved PFS in patients undergoing 2D-RT raises doubts regarding the adequacy of target delineation in these neoplasms.","Source":"PubMed","category":"HUMAN","training_data":"Radiotherapy or Chemoradiation in Unresectable Biliary Cancer: A Retrospective Study BACKGROUND/AIM: To retrospectively evaluate the outcome of patients with unresectable biliary cholangiocarcinoma (CC) treated with radiotherapy (RT) plus/minus chemotherapy (CHT). MATERIALS AND METHODS: Data of patients with intrahepatic CC (ICC), Klatskin's tumor (KT), distal extrahepatic CC (ECC), and gallbladder cancer (GBC) diagnosed from 1991 to 2017 were retrospectively analyzed. The treatment was mainly based on RT plus concurrent CHT +/- brachytherapy (BRT) boost. The Kaplan-Meier method was used to calculate survival curves that were compared using the log-rank test. RESULTS: Seventy-six patients were included in this analysis (males: 59%; females: 41%; median age: 66.5 years). A minority of patients (7.9%) were treated for disease recurrence after surgery. According to TNM, 78.5% of patients had T stage >3 and 77.6% of patients were treated with concurrent CHT-RT while 22.3% received RT followed by sequential CHT. Median RT dose was 50 Gy (range: 16-75 Gy) delivered with conventional fractionation. CHT was based on Gemcitabine or 5-fluorouracil. BRT was prescribed to 51.3% of patient with a median dose of 14 Gy. Reported Grade ≥3 acute GI and hematological toxicity were 13.2% and 8.1%, respectively. No other severe acute toxicities were reported. One- and 2-year overall survival (OS) were 58.1% and 25.8%, respectively (median: 13.5 months), while 1- and 2-year progression-free survival (PFS) were 43.4% and 9.4%, respectively. None of the following variables had a significant impact on OS and PFS: BRT boost, tumor site, concurrent CHT, and the drugs used in concurrent CHT. In contrast, patients receiving RT with 2D technique showed a PFS significantly higher compared to patients treated with the 3D technique (median: 15.5 vs. 8.5 months; p=0.02). CONCLUSION: Combined modality treatment (RT+CHT±BRT) in unresectable biliary cancer was associated with acceptable toxicity and OS comparable to the actual standard treatment (CHT). The significantly improved PFS in patients undergoing 2D-RT raises doubts regarding the adequacy of target delineation in these neoplasms. PubMed","prediction_labels":"HUMAN"},{"cleaned":"value indocyanine green clearance future liver remnant predicting outcome resection biliary cancer background difficult predict hepatic functional reserve accurately major hepatectomy aim study analyse usefulness future liver remnant plasma clearance rate indocyanine green icgk f calculated plasma clearance rate indocyanine green icgk x proportion future liver remnant predicting death major hepatectomy methods data icgk icgk f collected prospectively analysed retrospectively 274 patients underwent right hepatectomy right trisectionectomy left trisectionectomy biliary cancer 1991 2008 mortality rate incidence postoperative complications analysed patients separated two groups according year operation 85 patients operated 1991 2000 189 2001 2008 results multiple logistic regression analyses icgk f less 0 05 strongest impact incidence postoperative mortality odds ratio 8 06 p 0 001 postoperative mortality rate significantly lower later period p 0 001 patients icgk f value 0 040 0 049 mortality rate early period 30 per cent whereas 8 per cent later period conclusion icgk f 0 05 useful cut value predicting mortality morbidity careful perioperative patient management experienced institution cut value lowered pubmed","probabilities":0.9799733,"Title":"Value of indocyanine green clearance of the future liver remnant in predicting outcome after resection for biliary cancer","Abstract":"BACKGROUND: It is difficult to predict hepatic functional reserve accurately before major hepatectomy. The aim of this study was to analyse the usefulness of the future liver remnant plasma clearance rate of indocyanine green (ICGK-F, calculated as plasma clearance rate of indocyanine green (ICGK) x proportion of the future liver remnant) in predicting death after major hepatectomy. METHODS: Data on ICGK and ICGK-F were collected prospectively and analysed retrospectively for 274 patients who underwent right hepatectomy, right trisectionectomy or left trisectionectomy for biliary cancer between 1991 and 2008. The mortality rate and incidence of postoperative complications were analysed. Patients were separated into two groups according to year of operation (85 patients operated on between 1991 and 2000; 189 from 2001 to 2008). RESULTS: In multiple logistic regression analyses, an ICGK-F less than 0.05 had the strongest impact on the incidence of postoperative mortality (odds ratio 8.06; P < 0.001). The postoperative mortality rate was significantly lower in the later period (P < 0.001). In patients with an ICGK-F value between 0.040 and 0.049, the mortality rate in the early period was 30 per cent, whereas it was only 8 per cent in the later period. CONCLUSION: An ICGK-F of 0.05 is a useful cut-off value for predicting mortality and morbidity. With careful perioperative patient management in an experienced institution, this cut-off value can be lowered further.","Source":"PubMed","category":"HUMAN","training_data":"Value of indocyanine green clearance of the future liver remnant in predicting outcome after resection for biliary cancer BACKGROUND: It is difficult to predict hepatic functional reserve accurately before major hepatectomy. The aim of this study was to analyse the usefulness of the future liver remnant plasma clearance rate of indocyanine green (ICGK-F, calculated as plasma clearance rate of indocyanine green (ICGK) x proportion of the future liver remnant) in predicting death after major hepatectomy. METHODS: Data on ICGK and ICGK-F were collected prospectively and analysed retrospectively for 274 patients who underwent right hepatectomy, right trisectionectomy or left trisectionectomy for biliary cancer between 1991 and 2008. The mortality rate and incidence of postoperative complications were analysed. Patients were separated into two groups according to year of operation (85 patients operated on between 1991 and 2000; 189 from 2001 to 2008). RESULTS: In multiple logistic regression analyses, an ICGK-F less than 0.05 had the strongest impact on the incidence of postoperative mortality (odds ratio 8.06; P < 0.001). The postoperative mortality rate was significantly lower in the later period (P < 0.001). In patients with an ICGK-F value between 0.040 and 0.049, the mortality rate in the early period was 30 per cent, whereas it was only 8 per cent in the later period. CONCLUSION: An ICGK-F of 0.05 is a useful cut-off value for predicting mortality and morbidity. With careful perioperative patient management in an experienced institution, this cut-off value can be lowered further. PubMed","prediction_labels":"HUMAN"},{"cleaned":"excretory secretory products carcinogenic liver fluke endocytosed human cholangiocytes drive cell proliferation il6 production liver fluke infection caused opisthorchis viverrini remains major public health problem many parts asia including thailand lao pdr vietnam cambodia strikingly high incidence cholangiocarcinoma cca hepatic cancer bile duct epithelium among factors uptake o viverrini excretory secretory products oves biliary epithelial cells postulated responsible chronic inflammation proliferation cholangiocytes mechanisms cells internalise o viverrini excretory secretory products still unknown herein incubated normal human cholangiocytes h69 human cholangiocarcinoma cells kku 100 kku m156 human colon cancer caco 2 cells o viverrini excretory secretory products analysed effects different endocytic inhibitors address mechanism cellular uptake es proteins opisthorchis viverrini excretory secretory products internalised preferentially liver cell lines efficiently rapidly h69 cells evidence trafficking es proteins cholangiocyte organelles fluorescence detected cytoplasm pretreatment clathrin inhibitors significantly reduced uptake o viverrini excretory secretory products particularly h69 cells opisthorchis viverrini excretory secretory products induced proliferation liver cells h69 cca lines intestinal caco 2 cells proliferation blocked using inhibitors classical endocytic pathways clathrin caveolae opisthorchis viverrini excretory secretory products drove il6 secretion h69 cells caco 2 cells cytokine secretion significantly reduced endocytosis inhibitors first known study address endocytosis helminth es proteins host epithelial cells sheds light pathways parasite causes one devastating forms cancer south eastern asia stn","probabilities":0.9467213,"Title":"Excretory/Secretory Products Of The Carcinogenic Liver Fluke Are Endocytosed By Human Cholangiocytes And Drive Cell Proliferation And Il6 Production","Abstract":"Liver fluke infection caused by Opisthorchis viverrini remains a major public health problem in many parts of Asia including Thailand, Lao PDR, Vietnam and Cambodia, where there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium). Among other factors, uptake of O. viverrini excretory/secretory products (OvES) by biliary epithelial cells has been postulated to be responsible for chronic inflammation and proliferation of cholangiocytes, but the mechanisms by which cells internalise O. viverrini excretory/secretory products are still unknown. Herein we incubated normal human cholangiocytes (H69), human cholangiocarcinoma cells (KKU-100, KKU-M156) and human colon cancer (Caco-2) cells with O. viverrini excretory/secretory products and analysed the effects of different endocytic inhibitors to address the mechanism of cellular uptake of ES proteins. Opisthorchis viverrini excretory/secretory products was internalised preferentially by liver cell lines, and most efficiently/rapidly by H69 cells. There was no evidence for trafficking of ES proteins to cholangiocyte organelles, and most of the fluorescence was detected in the cytoplasm. Pretreatment with clathrin inhibitors significantly reduced the uptake of O. viverrini excretory/secretory products, particularly by H69 cells. Opisthorchis viverrini excretory/secretory products induced proliferation of liver cells (H69 and CCA lines) but not intestinal (Caco-2) cells, and proliferation was blocked using inhibitors of the classical endocytic pathways (clathrin and caveolae). Opisthorchis viverrini excretory/secretory products drove IL6 secretion by H69 cells but not Caco-2 cells, and cytokine secretion was significantly reduced by endocytosis inhibitors. This the first known study to address the endocytosis of helminth ES proteins by host epithelial cells and sheds light on the pathways by which this parasite causes one of the most devastating forms of cancer in south-eastern Asia.","Source":"STN","category":"ANIMAL","training_data":"Excretory/Secretory Products Of The Carcinogenic Liver Fluke Are Endocytosed By Human Cholangiocytes And Drive Cell Proliferation And Il6 Production Liver fluke infection caused by Opisthorchis viverrini remains a major public health problem in many parts of Asia including Thailand, Lao PDR, Vietnam and Cambodia, where there is a strikingly high incidence of cholangiocarcinoma (CCA - hepatic cancer of the bile duct epithelium). Among other factors, uptake of O. viverrini excretory/secretory products (OvES) by biliary epithelial cells has been postulated to be responsible for chronic inflammation and proliferation of cholangiocytes, but the mechanisms by which cells internalise O. viverrini excretory/secretory products are still unknown. Herein we incubated normal human cholangiocytes (H69), human cholangiocarcinoma cells (KKU-100, KKU-M156) and human colon cancer (Caco-2) cells with O. viverrini excretory/secretory products and analysed the effects of different endocytic inhibitors to address the mechanism of cellular uptake of ES proteins. Opisthorchis viverrini excretory/secretory products was internalised preferentially by liver cell lines, and most efficiently/rapidly by H69 cells. There was no evidence for trafficking of ES proteins to cholangiocyte organelles, and most of the fluorescence was detected in the cytoplasm. Pretreatment with clathrin inhibitors significantly reduced the uptake of O. viverrini excretory/secretory products, particularly by H69 cells. Opisthorchis viverrini excretory/secretory products induced proliferation of liver cells (H69 and CCA lines) but not intestinal (Caco-2) cells, and proliferation was blocked using inhibitors of the classical endocytic pathways (clathrin and caveolae). Opisthorchis viverrini excretory/secretory products drove IL6 secretion by H69 cells but not Caco-2 cells, and cytokine secretion was significantly reduced by endocytosis inhibitors. This the first known study to address the endocytosis of helminth ES proteins by host epithelial cells and sheds light on the pathways by which this parasite causes one of the most devastating forms of cancer in south-eastern Asia. STN","prediction_labels":"ANIMAL"},{"cleaned":"en bloc resection hepatoduodenal ligament advanced biliary malignancy background en bloc resection hepatoduodenal ligament hdl advanced biliary malignancy hepato ligamento pancreatoduodenectomy hlpd hepatoligamentectomy hl remains challenging short term outcomes reported showed surgical technique hlpd hl retrospectively investigated surgical outcomes patients methods 2003 2014 performed four hlpd three hl including major hepatectomy concomitant caudate lobectomy portal vein reconstruction pvr performed right external iliac vein graft hepatic artery reconstruction har accomplished heterogeneous artery using continuous suturing method results mean operation time blood loss 575 111 min 1539 950 ml respectively patency reconstructed vessels confirmed postoperatively cases histologically negative surgical margins r0 achieved 57 patients resected vascular invasion confirmed patients overall morbidity high 57 achieved postoperative mortality overall median survival time patients 36 months patient hl survived 5 years conclusions en bloc resection hdl based steady vascular reconstruction improve surgical outcome biliary cancer selected patients pubmed","probabilities":0.9799733,"Title":"En bloc resection of the hepatoduodenal ligament for advanced biliary malignancy","Abstract":"BACKGROUND: En bloc resection of the hepatoduodenal ligament (HDL) for advanced biliary malignancy by hepato-ligamento-pancreatoduodenectomy (HLPD) or hepatoligamentectomy (HL) remains challenging, and only short-term outcomes have been reported. We showed our surgical technique of HLPD and HL, and retrospectively investigated surgical outcomes of the patients. METHODS: Between 2003 and 2014, we performed four HLPD and three HL including major hepatectomy with concomitant caudate lobectomy. Portal vein reconstruction (PVR) was performed with a right external iliac vein graft, and hepatic artery reconstruction (HAR) was accomplished with the heterogeneous artery using the continuous suturing method. RESULTS: Mean operation time and blood loss were 575 ± 111 min and 1539 ± 950 mL, respectively, and patency of the reconstructed vessels was confirmed postoperatively in all cases. Histologically, negative surgical margins (R0) were achieved in 57% of patients, while the resected vascular invasion was confirmed in all patients. Overall morbidity was high at 57%, but we have achieved no postoperative mortality. Overall median survival time of the patients was 36 months, and a patient of HL survived over 5 years. CONCLUSIONS: En bloc resection of the HDL based on steady vascular reconstruction can improve the surgical outcome of biliary cancer in selected patients.","Source":"PubMed","category":"HUMAN","training_data":"En bloc resection of the hepatoduodenal ligament for advanced biliary malignancy BACKGROUND: En bloc resection of the hepatoduodenal ligament (HDL) for advanced biliary malignancy by hepato-ligamento-pancreatoduodenectomy (HLPD) or hepatoligamentectomy (HL) remains challenging, and only short-term outcomes have been reported. We showed our surgical technique of HLPD and HL, and retrospectively investigated surgical outcomes of the patients. METHODS: Between 2003 and 2014, we performed four HLPD and three HL including major hepatectomy with concomitant caudate lobectomy. Portal vein reconstruction (PVR) was performed with a right external iliac vein graft, and hepatic artery reconstruction (HAR) was accomplished with the heterogeneous artery using the continuous suturing method. RESULTS: Mean operation time and blood loss were 575 ± 111 min and 1539 ± 950 mL, respectively, and patency of the reconstructed vessels was confirmed postoperatively in all cases. Histologically, negative surgical margins (R0) were achieved in 57% of patients, while the resected vascular invasion was confirmed in all patients. Overall morbidity was high at 57%, but we have achieved no postoperative mortality. Overall median survival time of the patients was 36 months, and a patient of HL survived over 5 years. CONCLUSIONS: En bloc resection of the HDL based on steady vascular reconstruction can improve the surgical outcome of biliary cancer in selected patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"endoscopic bilateral stent stent placement malignant hilar obstruction using large cell type stent background bilateral stent stent sis self expandable metal stent placement technically challenging palliation unresectable malignant hilar obstruction sis technique uniform large cell type biliary stent facilitates contralateral stent deployment mesh first metallic stent study aimed assess technical success clinical effectiveness technique uniform large cell type biliary stent methods thirty one patients underwent bilateral sis placement using large cell type stent reviewed retrospectively patients showed malignant hilar obstruction bismuth types ii iii iv different etiologies results sixteen 51 6 patients male mean age patients 67 0 14 0 years patients diagnosed hilar cholangiocarcinoma 58 1 gallbladder cancer 29 0 technical success rate 83 9 success achieved frequently patients without masses obstructing biliary confluence moc moc 95 2 vs 60 0 p 0 03 functional success rate 77 4 complications occurred 29 0 patients tended occur frequently patients moc 50 0 vs 19 0 p 0 11 median time recurrent biliary obstruction 188 days median survival 175 days conclusions large cell type stent used efficiently bilateral sis placement malignant hilar obstruction however risk technical failure increases patients moc caution needed prevent complications patients pubmed","probabilities":0.962963,"Title":"Endoscopic bilateral stent-in-stent placement for malignant hilar obstruction using a large cell type stent","Abstract":"BACKGROUND: Bilateral stent-in-stent (SIS) self-expandable metal stent placement is technically challenging for palliation of unresectable malignant hilar obstruction. In the SIS technique, the uniform large cell type biliary stent facilitates contralateral stent deployment through the mesh of the first metallic stent. This study aimed to assess the technical success and clinical effectiveness of this technique with a uniform large cell type biliary stent. METHODS: Thirty-one patients who underwent bilateral SIS placement using a large cell type stent were reviewed retrospectively. All patients showed malignant hilar obstruction (Bismuth types II, III, IV) with different etiologies. RESULTS: Sixteen (51.6%) patients were male. The mean age of the patients was 67.0+/-14.0 years. Most patients were diagnosed as having hilar cholangiocarcinoma (58.1%) and gallbladder cancer (29.0%). Technical success rate was 83.9%. Success was achieved more frequently in patients without masses obstructing the biliary confluence (MOC) than those with MOC (95.2% vs 60.0%, P=0.03). Functional success rate was 77.4%. Complications occurred in 29.0% of the patients. These tended to occur more frequently in patients with MOC (50.0% vs 19.0%, P=0.11). Median time to recurrent biliary obstruction was 188 days and median survival was 175 days. CONCLUSIONS: The large cell type stent can be used efficiently for bilateral SIS placement in malignant hilar obstruction. However, the risk of technical failure increases in patients with MOC, and caution is needed to prevent complications for these patients.","Source":"PubMed","category":"HUMAN","training_data":"Endoscopic bilateral stent-in-stent placement for malignant hilar obstruction using a large cell type stent BACKGROUND: Bilateral stent-in-stent (SIS) self-expandable metal stent placement is technically challenging for palliation of unresectable malignant hilar obstruction. In the SIS technique, the uniform large cell type biliary stent facilitates contralateral stent deployment through the mesh of the first metallic stent. This study aimed to assess the technical success and clinical effectiveness of this technique with a uniform large cell type biliary stent. METHODS: Thirty-one patients who underwent bilateral SIS placement using a large cell type stent were reviewed retrospectively. All patients showed malignant hilar obstruction (Bismuth types II, III, IV) with different etiologies. RESULTS: Sixteen (51.6%) patients were male. The mean age of the patients was 67.0+/-14.0 years. Most patients were diagnosed as having hilar cholangiocarcinoma (58.1%) and gallbladder cancer (29.0%). Technical success rate was 83.9%. Success was achieved more frequently in patients without masses obstructing the biliary confluence (MOC) than those with MOC (95.2% vs 60.0%, P=0.03). Functional success rate was 77.4%. Complications occurred in 29.0% of the patients. These tended to occur more frequently in patients with MOC (50.0% vs 19.0%, P=0.11). Median time to recurrent biliary obstruction was 188 days and median survival was 175 days. CONCLUSIONS: The large cell type stent can be used efficiently for bilateral SIS placement in malignant hilar obstruction. However, the risk of technical failure increases in patients with MOC, and caution is needed to prevent complications for these patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"systemic lupus erythematosus malignancies risk objective evaluate risk site specific overall malignancies sle explore potential influencing factors methods searched electronic databases articles assessed risk malignancies sle february 2015 extracted incidence rates irs corresponding 95 confidence intervals cis used random effects models calculate pooled irs assessed impact study designs region gender age duration follow results eighteen studies included giving pooled ir 1 44 95 ci 1 23 1 69 europeans americans asians showed ir 1 56 95 ci 1 07 2 28 1 18 95 ci 1 01 1 39 1 62 95 ci 1 38 1 89 respectively males females eight studies demonstrated ir 1 34 95 ci 1 07 1 67 1 51 95 ci 1 20 1 90 respectively prospective retrospective studies showed ir 1 55 95 ci 0 97 2 47 1 44 95 ci 1 21 1 73 respectively increment 10 years age conferred decrease ir 0 6 increment 5 years sle duration conferred decrease ir 2 5 increased ir malignancies observed nhl vagina vulva hematology head neck leukemia thyroid liver gallbladder kidney anal cervix esophagus lung pancreas decreased ir malignancies observed ovary colon rectum conclusions sle patients increased risk developing overall malignancies particularly among asians females age sle duration inversely associated risk overall malignancies sle patients showed different role onset various site specific malignancies pubmed","probabilities":0.9799733,"Title":"Systemic lupus erythematosus and malignancies risk","Abstract":"OBJECTIVE: To evaluate the risk of site-specific and overall malignancies after SLE and explore the potential influencing factors. METHODS: We searched electronic databases for articles that assessed the risk of malignancies after SLE through February 2015. We extracted the incidence rates (IRs) and corresponding 95 % confidence intervals (CIs). We used random effects models to calculate the pooled IRs and assessed the impact of study designs, region, gender, age and duration of follow-up. RESULTS: Eighteen studies were included, giving a pooled IR of 1.44 (95 % CI 1.23-1.69). Europeans, Americans and Asians showed a IR of 1.56 (95 % CI 1.07-2.28), 1.18 (95 % CI 1.01-1.39) and 1.62 (95 % CI 1.38-1.89), respectively. Males and females (eight studies) demonstrated a IR of 1.34 (95 % CI 1.07-1.67) and 1.51 (95 % CI 1.20-1.90), respectively. Prospective and retrospective studies showed a IR of 1.55 (95 % CI 0.97-2.47) and 1.44 (95 % CI 1.21-1.73), respectively. An increment of 10 years of age conferred a decrease in IR of 0.6. An increment of 5 years of SLE duration conferred a decrease in IR of 2.5. An increased IR of malignancies was observed in NHL, vagina/vulva, hematology, head/neck, leukemia, thyroid, liver/gallbladder, kidney, anal, cervix, esophagus, lung and pancreas. A decreased IR of malignancies was observed in ovary and colon/rectum. CONCLUSIONS: SLE patients had an increased risk of developing overall malignancies, particularly among Asians and females. Age and SLE duration are inversely associated with the risk of overall malignancies. SLE patients showed a different role in the onset of various site-specific malignancies.","Source":"PubMed","category":"HUMAN","training_data":"Systemic lupus erythematosus and malignancies risk OBJECTIVE: To evaluate the risk of site-specific and overall malignancies after SLE and explore the potential influencing factors. METHODS: We searched electronic databases for articles that assessed the risk of malignancies after SLE through February 2015. We extracted the incidence rates (IRs) and corresponding 95 % confidence intervals (CIs). We used random effects models to calculate the pooled IRs and assessed the impact of study designs, region, gender, age and duration of follow-up. RESULTS: Eighteen studies were included, giving a pooled IR of 1.44 (95 % CI 1.23-1.69). Europeans, Americans and Asians showed a IR of 1.56 (95 % CI 1.07-2.28), 1.18 (95 % CI 1.01-1.39) and 1.62 (95 % CI 1.38-1.89), respectively. Males and females (eight studies) demonstrated a IR of 1.34 (95 % CI 1.07-1.67) and 1.51 (95 % CI 1.20-1.90), respectively. Prospective and retrospective studies showed a IR of 1.55 (95 % CI 0.97-2.47) and 1.44 (95 % CI 1.21-1.73), respectively. An increment of 10 years of age conferred a decrease in IR of 0.6. An increment of 5 years of SLE duration conferred a decrease in IR of 2.5. An increased IR of malignancies was observed in NHL, vagina/vulva, hematology, head/neck, leukemia, thyroid, liver/gallbladder, kidney, anal, cervix, esophagus, lung and pancreas. A decreased IR of malignancies was observed in ovary and colon/rectum. CONCLUSIONS: SLE patients had an increased risk of developing overall malignancies, particularly among Asians and females. Age and SLE duration are inversely associated with the risk of overall malignancies. SLE patients showed a different role in the onset of various site-specific malignancies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"high prevalence asbestos exposure bile duct cancer patients background asbestos exposure well recognized risk factor mesothelioma lung cancer development association tumors gastrointestinal bile ducts cancers btc uncertain univocally demonstrated asbestos fibers cross alveolar barrier inhalation penetrate gastrointestinal mucosa ingestion reach interstitial environment circulatory system finally delivered tissues including liver bile ducts work aims evaluating potential correlation previous asbestos exposure btc occurrence methods previous year carefully interviewed 70 consecutive btc patients using standardized questionnaire asking exposure asbestos known risk factors linked bile duct carcinogenesis results addition association known risk factors onset btc observed occupational household exposure asbes tos 25 patients 36 11 intrahepatic icc 8 extrahepatic ecc 6 patients gallbladder cancer gbc 11 patients certain risk factors remaining 14 patients presented hcv chronic infection exposure proven suspected carcinogenic compounds primary sclerosing cholangitis occupational exposure occurred 5 11 icc 4 8 ecc household exposure noticed 7 11 icc 4 8 ecc 6 6 gbc one icc patient exposure type conclusions substantial proportion btc patients history asbestos exposure studies clarify putative relation perhaps explain increasing incidence icc western countries observed last decades google scholar","probabilities":0.88235295,"Title":"High Prevalence Of Asbestos Exposure In Bile Duct Cancer Patients","Abstract":"Background: Asbestos exposure is a well recognized risk factor in mesothelioma and lung cancer development but the association with other tumors, such as gastrointestinal and bile ducts cancers (BTC), is uncertain and has not been univocally demonstrated. Asbestos fibers can cross the alveolar barrier after inhalation and penetrate the gastrointestinal mucosa by ingestion. Than they can reach the interstitial environment, the circulatory system and are finally delivered to all tissues, including liver and bile ducts. This work aims at evaluating the potential correlation between previous asbestos exposure and BTC occurrence.\nMethods: Over the previous year, we carefully interviewed 70 consecutive BTC patients using a standardized questionnaire asking about their exposure to asbestos and other known risk factors linked to bile duct carcinogenesis.\nResults: In addition to the association with known risk factors for the onset of BTC, we observed occupational or household exposure to asbes-tos in 25 patients (36%), 11 of whom were intrahepatic (ICC), 8 extrahepatic (ECC) and 6 patients had gallbladder cancer (GBC). 11 patients did not have other certain risk factors. The remaining 14 patients presented HCV chronic infection, exposure to proven or suspected carcinogenic compounds, or primary sclerosing cholangitis. Occupational exposure occurred in 5/11 ICC and 4/8 ECC; household exposure was noticed in 7/11 ICC, 4/8 ECC and 6/6 GBC. Only one ICC patient had both exposure type.\nConclusions: A substantial proportion of BTC patients had an history of asbestos exposure. Further studies could clarify this putative relation and perhaps explain the increasing incidence of ICC in Western countries observed during the last decades.","Source":"Google Scholar","category":"HUMAN","training_data":"High Prevalence Of Asbestos Exposure In Bile Duct Cancer Patients Background: Asbestos exposure is a well recognized risk factor in mesothelioma and lung cancer development but the association with other tumors, such as gastrointestinal and bile ducts cancers (BTC), is uncertain and has not been univocally demonstrated. Asbestos fibers can cross the alveolar barrier after inhalation and penetrate the gastrointestinal mucosa by ingestion. Than they can reach the interstitial environment, the circulatory system and are finally delivered to all tissues, including liver and bile ducts. This work aims at evaluating the potential correlation between previous asbestos exposure and BTC occurrence.\nMethods: Over the previous year, we carefully interviewed 70 consecutive BTC patients using a standardized questionnaire asking about their exposure to asbestos and other known risk factors linked to bile duct carcinogenesis.\nResults: In addition to the association with known risk factors for the onset of BTC, we observed occupational or household exposure to asbes-tos in 25 patients (36%), 11 of whom were intrahepatic (ICC), 8 extrahepatic (ECC) and 6 patients had gallbladder cancer (GBC). 11 patients did not have other certain risk factors. The remaining 14 patients presented HCV chronic infection, exposure to proven or suspected carcinogenic compounds, or primary sclerosing cholangitis. Occupational exposure occurred in 5/11 ICC and 4/8 ECC; household exposure was noticed in 7/11 ICC, 4/8 ECC and 6/6 GBC. Only one ICC patient had both exposure type.\nConclusions: A substantial proportion of BTC patients had an history of asbestos exposure. Further studies could clarify this putative relation and perhaps explain the increasing incidence of ICC in Western countries observed during the last decades. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"histomorphologic molecular phenotypes predict gemcitabine response overall survival adenocarcinoma ampulla vater background need adjuvant chemotherapy resection ampullary cancer papca remains undefined recent data suggest different epithelial origin papca might associated different tumor biology aim present study assess clinical value morphologic immunohistochemic subclassification papca intestinal type pancreaticobiliary type pt predict chemotherapy response overall survival os methods via prospective database 112 papca identified 95 included present study compared 206 matching patients periampullary pancreatic cancer ie pancreatic ductal adenocarcinoma pdac pt papca classified morphologically tissue microarray prepared immunohistochemistry ck7 ck20 muc2 cdx2 catenin villin multivariate survival analysis performed results os pt patients less compared patients 25 vs 98 months p 001 whereas comparable patients pdac 25 vs 14 months p 123 pt patients receiving adjuvant gemcitabine chemotherapy featured improved os 32 vs 13 months p 013 whereas gemcitabine tended associated decreased os patients 35 vs 112 months p 193 besides histopathologic classification expression ck7 muc2 important prognostic variables pt patients ck7 positivity muc2 negativity segregated even poorer prognostic group conclusion papca separate tumor entity demonstrate important differences papca pt papca long term survival also response adjuvant gemcitabine tumor biology clinical course pt tumors resemble pdac pt tumors therefore treated like pdac pubmed","probabilities":0.7966102,"Title":"Histomorphologic and molecular phenotypes predict gemcitabine response and overall survival in adenocarcinoma of the ampulla of Vater","Abstract":"BACKGROUND: The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS). METHODS: Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study. Those were compared with 206 matching patients with periampullary pancreatic cancer (ie, pancreatic ductal adenocarcinoma, PDAC). IT and PT PapCa were classified morphologically, and tissue microarray was prepared with immunohistochemistry for CK7, CK20, MUC2, CDX2, ß-Catenin, and Villin. Multivariate survival analysis was performed. RESULTS: OS of PT patients was less compared with IT patients (25 vs 98 months; P < .001), whereas it was comparable with patients with PDAC (25 vs 14 months; P = .123). PT patients receiving adjuvant gemcitabine chemotherapy featured improved OS (32 vs 13 months; P = .013), whereas gemcitabine tended to be associated with decreased OS in IT patients (35 vs 112 months; P = .193). Besides histopathologic classification, expression of CK7 and MUC2 were important prognostic variables. PT patients with CK7-positivity or MUC2-negativity were segregated into an even poorer prognostic group. CONCLUSION: PapCa is not a separate tumor entity. We demonstrate important differences between IT-PapCa and PT-PapCa not only in long-term survival but also in response to adjuvant gemcitabine. Tumor biology and clinical course of PT tumors resemble those of PDAC. PT tumors should therefore be treated like PDAC.","Source":"PubMed","category":"HUMAN","training_data":"Histomorphologic and molecular phenotypes predict gemcitabine response and overall survival in adenocarcinoma of the ampulla of Vater BACKGROUND: The need for adjuvant chemotherapy after resection of ampullary cancer (PapCa) remains undefined. Recent data suggest that a different epithelial origin of PapCa might be associated with different tumor biology. The aim of the present study was to assess the clinical value of morphologic and immunohistochemic subclassification of PapCa into intestinal-type (IT) and pancreaticobiliary-type (PT) to predict chemotherapy response and overall survival (OS). METHODS: Via a prospective database, 112 PapCa were identified, of which 95 could be included in the present study. Those were compared with 206 matching patients with periampullary pancreatic cancer (ie, pancreatic ductal adenocarcinoma, PDAC). IT and PT PapCa were classified morphologically, and tissue microarray was prepared with immunohistochemistry for CK7, CK20, MUC2, CDX2, ß-Catenin, and Villin. Multivariate survival analysis was performed. RESULTS: OS of PT patients was less compared with IT patients (25 vs 98 months; P < .001), whereas it was comparable with patients with PDAC (25 vs 14 months; P = .123). PT patients receiving adjuvant gemcitabine chemotherapy featured improved OS (32 vs 13 months; P = .013), whereas gemcitabine tended to be associated with decreased OS in IT patients (35 vs 112 months; P = .193). Besides histopathologic classification, expression of CK7 and MUC2 were important prognostic variables. PT patients with CK7-positivity or MUC2-negativity were segregated into an even poorer prognostic group. CONCLUSION: PapCa is not a separate tumor entity. We demonstrate important differences between IT-PapCa and PT-PapCa not only in long-term survival but also in response to adjuvant gemcitabine. Tumor biology and clinical course of PT tumors resemble those of PDAC. PT tumors should therefore be treated like PDAC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"egfr flt1 heparanase markers identifying patients risk short survival cholangiocarcinoma background cholangiocarcinoma remains tumor treatment choices limited prognosis study sought determine prognostic role fms related tyrosine kinase 1 vascular endothelial growth factor receptor 1 flt1 vegfr1 heparanase hpse epidermal growth factor receptor egfr gene expression patients resected ccc methods 47 formalin fixed paraffin embedded ffpe tumor samples patients resected ccc analyzed ffpe tissues dissected using laser captured microdissection analyzed flt1 flt4 hpse hif1a vegfa c hb egf pdgfa pdgf ra egfr mrna expression using quantitative real time rt pcr method gene expression values relative mrna levels expressed ratios target gene internal reference genes beta actin b2mg rplp2 sdha results egfr flt1 hpse expression levels significantly associated overall survival os flt1 showed strongest significant independent association overall survival multivariate cox regression analysis compared genes clinicopathological factors nearly 5 times higher relative risk 4 74 dying earlier expressed low levels p 0 04 roc curve analysis revealed measuring egfr potentially identifies patients risk worsened outcome sensitivity 80 specificity 75 p 0 01 conclusions egfr flt1 seem potential markers identify patients high risk dying cholangiocarcinoma therefore markers may help identify patient subgroups need aggressive approach disease desperate need new approaches stn","probabilities":0.88235295,"Title":"Egfr Flt1 And Heparanase As Markers Identifying Patients At Risk Of Short Survival In Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinoma remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of fms-related tyrosine kinase 1/vascular endothelial growth factor receptor 1 (FLT1/VEGFR1), heparanase (HPSE) and epidermal growth factor receptor (EGFR) gene expression in patients with resected CCC. \r\n\r\n Methods: 47 formalin-fixed paraffin embedded FFPE tumor samples from patients with resected CCC were analyzed. FFPE tissues were dissected using laser-captured microdissection and analyzed for FLT1, FLT4, HPSE, Hif1a, VEGFA/C, HB-EGF, PDGFA, PDGF-RA and EGFR mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference genes (beta-actin, b2mg, rplp2, sdha). \r\n\r\n Results: EGFR, FLT1 and HPSE expression levels were significantly associated with overall survival (OS). FLT1 showed the strongest significant independent association with overall survival in a multivariate cox regression analysis when compared to the other genes and clinicopathological factors with a nearly 5 times higher relative risk (4.74) of dying earlier when expressed in low levels (p = 0.04). ROC Curve Analysis revealed that measuring EGFR potentially identifies patients at risk of a worsened outcome with a sensitivity of 80% and a specificity of 75% (p = 0.01). \r\n\r\n Conclusions: EGFR and FLT1 seem to be potential markers to identify those patients at high risk of dying from cholangiocarcinoma. Therefore these markers may help to identify patient subgroups in need for a more aggressive approach in a disease that is in desperate need for new approaches.","Source":"STN","category":"ANIMAL","training_data":"Egfr Flt1 And Heparanase As Markers Identifying Patients At Risk Of Short Survival In Cholangiocarcinoma Background: Cholangiocarcinoma remains to be a tumor with very few treatment choices and limited prognosis. In this study, we sought to determine the prognostic role of fms-related tyrosine kinase 1/vascular endothelial growth factor receptor 1 (FLT1/VEGFR1), heparanase (HPSE) and epidermal growth factor receptor (EGFR) gene expression in patients with resected CCC. \r\n\r\n Methods: 47 formalin-fixed paraffin embedded FFPE tumor samples from patients with resected CCC were analyzed. FFPE tissues were dissected using laser-captured microdissection and analyzed for FLT1, FLT4, HPSE, Hif1a, VEGFA/C, HB-EGF, PDGFA, PDGF-RA and EGFR mRNA expression using a quantitative real-time RT-PCR method. Gene expression values (relative mRNA levels) are expressed as ratios between the target gene and internal reference genes (beta-actin, b2mg, rplp2, sdha). \r\n\r\n Results: EGFR, FLT1 and HPSE expression levels were significantly associated with overall survival (OS). FLT1 showed the strongest significant independent association with overall survival in a multivariate cox regression analysis when compared to the other genes and clinicopathological factors with a nearly 5 times higher relative risk (4.74) of dying earlier when expressed in low levels (p = 0.04). ROC Curve Analysis revealed that measuring EGFR potentially identifies patients at risk of a worsened outcome with a sensitivity of 80% and a specificity of 75% (p = 0.01). \r\n\r\n Conclusions: EGFR and FLT1 seem to be potential markers to identify those patients at high risk of dying from cholangiocarcinoma. Therefore these markers may help to identify patient subgroups in need for a more aggressive approach in a disease that is in desperate need for new approaches. STN","prediction_labels":"HUMAN"},{"cleaned":"evaluation p53 e cadherin cox 2 egfr protein immunoexpression prognostic resected gallbladder carcinoma background gallbladder carcinoma presents dismal prognosis choice treatment surgical resection associated high levels morbidity mortality best knowledgement prognostic factors may result better selection patients either surgical multimodal treatment aim evaluate tecidual immunoexpression p53 e cadherin cox 2 egfr proteins correlate findings resected gallbladder adenocarcinoma survival methods clinical laboratorial surgical anatomopathological reports series gallbladder adenocarcinoma patients collected individualized questionary total sample 42 patients median age 72 years 35 87 seven men 35 women lesion distribuition according tnm state following t1 n 2 t2 n 5 t3 n 31 t4 n 4 twenty three patients underwent radical resection r0 19 palliative surgery r1 r2 block tissue microarray neoplasic tissue patient confected performed evaluation p53 e caderine cox 2 egfr proteins imunoexpression findings correlated overall survival results five year survival 28 median global survival eight months immunoexpression egfr protein considered independent variable multivariated analysis conclusion final prognosis influenced expression egfr protein tumoral tissue pubmed","probabilities":0.7966102,"Title":"Evaluation of P53, E-cadherin, Cox-2, and EGFR protein immunoexpression on prognostic of resected gallbladder carcinoma","Abstract":"BACKGROUND: Gallbladder carcinoma presents a dismal prognosis. Choice treatment is surgical resection that is associated a high levels of both morbidity and mortality. Best knowledgement of prognostic factors may result a better selection of patients either for surgical or multimodal treatment. AIM: To evaluate tecidual immunoexpression of P53, E-cadherin, Cox-2, and EGFR proteins and to correlate these findings with resected gallbladder adenocarcinoma survival. METHODS: Clinical, laboratorial, surgical, and anatomopathological reports of a series of gallbladder adenocarcinoma patients were collected by individualized questionary. Total sample was 42 patients. Median of age was 72 years (35-87). There were seven men and 35 women. Lesion distribuition in according TNM state was the following: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Twenty-three patients underwent radical resection (R0), while 19 palliative surgery (R1-R2). A block of tissue microarray with neoplasic tissue of each patient was confected. It was performed evaluation of P53, E-Caderine, COX-2, and EGFR proteins imunoexpression. These findings were correlated with overall survival. RESULTS: Five-year survival was 28%. The median of global survival was eight months. Only immunoexpression of EGFR protein was considered independent variable at multivariated analysis. CONCLUSION: Final prognosis was influenced by over-expression of EGFR protein in tumoral tissue.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of P53, E-cadherin, Cox-2, and EGFR protein immunoexpression on prognostic of resected gallbladder carcinoma BACKGROUND: Gallbladder carcinoma presents a dismal prognosis. Choice treatment is surgical resection that is associated a high levels of both morbidity and mortality. Best knowledgement of prognostic factors may result a better selection of patients either for surgical or multimodal treatment. AIM: To evaluate tecidual immunoexpression of P53, E-cadherin, Cox-2, and EGFR proteins and to correlate these findings with resected gallbladder adenocarcinoma survival. METHODS: Clinical, laboratorial, surgical, and anatomopathological reports of a series of gallbladder adenocarcinoma patients were collected by individualized questionary. Total sample was 42 patients. Median of age was 72 years (35-87). There were seven men and 35 women. Lesion distribuition in according TNM state was the following: T1 (n=2), T2 (n=5), T3 (n=31), T4 (n=4). Twenty-three patients underwent radical resection (R0), while 19 palliative surgery (R1-R2). A block of tissue microarray with neoplasic tissue of each patient was confected. It was performed evaluation of P53, E-Caderine, COX-2, and EGFR proteins imunoexpression. These findings were correlated with overall survival. RESULTS: Five-year survival was 28%. The median of global survival was eight months. Only immunoexpression of EGFR protein was considered independent variable at multivariated analysis. CONCLUSION: Final prognosis was influenced by over-expression of EGFR protein in tumoral tissue. PubMed","prediction_labels":"HUMAN"},{"cleaned":"precision hepatic arterial irinotecan therapy treatment unresectable intrahepatic cholangiocellular carcinoma optimal tolerance prolonged overall survival background unresectable intrahepatic cholangiocellular carcinoma icc carries poor prognosis chemotherapeutic treatments prolong survival purpose study assess efficacy drug eluting bead deb therapy transarterial infusion unresectable icc methods prospective multicenter study icc patients received hepatic arterial deb therapy results twenty four patients unresectable icc treated deb ten patients 41 6 recurrent icc prior radiofrequency ablation n 3 hepatectomy n 7 twenty patients 80 received prior chemotherapy mostly gemcitabine n 8 eloxatin n 6 percent overall liver involvement 25 n 8 26 50 n 11 50 n 4 ten patients 40 sites extrahepatic disease located lymph nodes n 5 bone n 2 peritoneum n 1 lung n 1 mouth n 1 total 42 deb treatments administered eight administered combination systemic chemotherapy folfox n 4 gemzar n 4 twelve patients 48 received second treatment 4 patients 16 received third treatment median length stay 23 h 23 72 h eleven adverse reactions 26 2 reported 7 63 6 minor less grade 3 one patient died hepatorenal syndrome disease one patient downstaged resection median follow 13 6 months median overall survival multitherapeutic regimen deb therapy significantly greater chemotherapy alone 17 5 vs 7 4 months p 0 02 conclusions bead therapy safe effective patients unresectable icc marked survival benefit deb therapy used adjunctive therapy pubmed","probabilities":0.9799733,"Title":"Precision hepatic arterial irinotecan therapy in the treatment of unresectable intrahepatic cholangiocellular carcinoma: optimal tolerance and prolonged overall survival","Abstract":"BACKGROUND: Unresectable intrahepatic cholangiocellular carcinoma (ICC) carries a poor prognosis, and there are few chemotherapeutic treatments to prolong survival. The purpose of this study was to assess the efficacy of drug-eluting bead (DEB) therapy by transarterial infusion for unresectable ICC. METHODS: A prospective multicenter study of ICC patients who received hepatic arterial DEB therapy. RESULTS: Twenty-four patients with unresectable ICC were treated with DEB. Ten patients (41.6%) had recurrent ICC after prior radiofrequency ablation (n = 3) or hepatectomy (n = 7). Twenty patients (80%) had received prior chemotherapy, mostly of gemcitabine (n = 8) or Eloxatin (n = 6). The percent of overall liver involvement was < 25% (n = 8), 26% to 50% (n = 11), and > 50% (n = 4). Ten patients (40%) had sites of extrahepatic disease located at lymph nodes (n = 5), bone (n = 2), peritoneum (n = 1), lung (n = 1), and mouth (n = 1). A total of 42 DEB treatments were administered. Eight were administered in combination with systemic chemotherapy of FOLFOX (n = 4) or Gemzar (n = 4). Twelve patients (48%) received a second treatment, and 4 patients (16%) received a third treatment. The median length of stay was 23 h (23-72 h). Eleven adverse reactions (26.2%) were reported. Of these, 7 (63.6%) were minor (less than grade 3). One patient died from hepatorenal syndrome. The disease of one patient was downstaged to resection. After a median follow-up of 13.6 months, the median overall survival of a multitherapeutic regimen with DEB therapy was significantly greater than chemotherapy alone (17.5 vs. 7.4 months; P = 0.02). CONCLUSIONS: Bead therapy is safe and effective in patients with unresectable ICC. There is a marked survival benefit when DEB therapy is used as adjunctive therapy.","Source":"PubMed","category":"HUMAN","training_data":"Precision hepatic arterial irinotecan therapy in the treatment of unresectable intrahepatic cholangiocellular carcinoma: optimal tolerance and prolonged overall survival BACKGROUND: Unresectable intrahepatic cholangiocellular carcinoma (ICC) carries a poor prognosis, and there are few chemotherapeutic treatments to prolong survival. The purpose of this study was to assess the efficacy of drug-eluting bead (DEB) therapy by transarterial infusion for unresectable ICC. METHODS: A prospective multicenter study of ICC patients who received hepatic arterial DEB therapy. RESULTS: Twenty-four patients with unresectable ICC were treated with DEB. Ten patients (41.6%) had recurrent ICC after prior radiofrequency ablation (n = 3) or hepatectomy (n = 7). Twenty patients (80%) had received prior chemotherapy, mostly of gemcitabine (n = 8) or Eloxatin (n = 6). The percent of overall liver involvement was < 25% (n = 8), 26% to 50% (n = 11), and > 50% (n = 4). Ten patients (40%) had sites of extrahepatic disease located at lymph nodes (n = 5), bone (n = 2), peritoneum (n = 1), lung (n = 1), and mouth (n = 1). A total of 42 DEB treatments were administered. Eight were administered in combination with systemic chemotherapy of FOLFOX (n = 4) or Gemzar (n = 4). Twelve patients (48%) received a second treatment, and 4 patients (16%) received a third treatment. The median length of stay was 23 h (23-72 h). Eleven adverse reactions (26.2%) were reported. Of these, 7 (63.6%) were minor (less than grade 3). One patient died from hepatorenal syndrome. The disease of one patient was downstaged to resection. After a median follow-up of 13.6 months, the median overall survival of a multitherapeutic regimen with DEB therapy was significantly greater than chemotherapy alone (17.5 vs. 7.4 months; P = 0.02). CONCLUSIONS: Bead therapy is safe and effective in patients with unresectable ICC. There is a marked survival benefit when DEB therapy is used as adjunctive therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"systematic underreporting population based incidence pancreatic biliary tract cancers background incidence rates cancers pancreas biliary tract typically derived cancer registers reported decreasing study tested whether pancreatic biliary tract cancers underreported swedish cancer register cr methods concordance pancreatic biliary tract cancer diagnoses 1990 2009 cr swedish patient register pr evaluated record linkage assess completeness cancer diagnoses cr pr record linkage also made swedish causes death register dr results total 31 067 cases pancreatic cancer 14 273 cases biliary tract cancer identified cr pr altogether 44 pancreatic cancers 44 biliary tract cancers registered pr cr concordance cr pr declined 63 years 1990 1994 44 2005 2009 pancreatic cancer corresponding figures biliary tract cancer 60 37 decline concordance also observed increasing age e g concordance cr pr pancreatic cancer declined 62 patients 60 years 36 among patients 80 years corresponding figures biliary tract cancer 52 38 conclusion overwhelming underreporting pancreatic biliary tract cancers within swedish cancer register increased recent years reported decreasing incidence rates pancreatic biliary tract cancers might therefore incorrect pubmed","probabilities":0.9799733,"Title":"Systematic underreporting of the population-based incidence of pancreatic and biliary tract cancers","Abstract":"BACKGROUND: Incidence rates of cancers of the pancreas and biliary tract, typically derived from cancer registers, have been reported to be decreasing. This study tested whether pancreatic and biliary tract cancers are underreported in the Swedish Cancer Register (CR). METHODS: The concordance of pancreatic and biliary tract cancer diagnoses in 1990-2009 between CR and the Swedish Patient Register (PR) were evaluated through record linkage. To further assess the completeness of these cancer diagnoses in both CR and PR, record linkage was also made to the Swedish Causes of Death Register (DR). RESULTS: A total of 31 067 cases of pancreatic cancer and 14 273 cases of biliary tract cancer were identified in CR or PR. Altogether, 44% of the pancreatic cancers and 44% of the biliary tract cancers were registered in PR only, and not in CR. The concordance between CR and PR declined from 63% in the years 1990-1994 to 44% in 2005-2009 for pancreatic cancer. The corresponding figures for biliary tract cancer were 60% and 37%. This decline in concordance was also observed with increasing age, e.g. the concordance between CR and PR for pancreatic cancer declined from 62% in patients<60 years to 36% among patients≥80 years. The corresponding figures for biliary tract cancer were 52% and 38%. CONCLUSION: There is an overwhelming underreporting of pancreatic and biliary tract cancers within the Swedish Cancer Register, which has increased during recent years. The reported decreasing incidence rates for pancreatic and biliary tract cancers might therefore be incorrect.","Source":"PubMed","category":"HUMAN","training_data":"Systematic underreporting of the population-based incidence of pancreatic and biliary tract cancers BACKGROUND: Incidence rates of cancers of the pancreas and biliary tract, typically derived from cancer registers, have been reported to be decreasing. This study tested whether pancreatic and biliary tract cancers are underreported in the Swedish Cancer Register (CR). METHODS: The concordance of pancreatic and biliary tract cancer diagnoses in 1990-2009 between CR and the Swedish Patient Register (PR) were evaluated through record linkage. To further assess the completeness of these cancer diagnoses in both CR and PR, record linkage was also made to the Swedish Causes of Death Register (DR). RESULTS: A total of 31 067 cases of pancreatic cancer and 14 273 cases of biliary tract cancer were identified in CR or PR. Altogether, 44% of the pancreatic cancers and 44% of the biliary tract cancers were registered in PR only, and not in CR. The concordance between CR and PR declined from 63% in the years 1990-1994 to 44% in 2005-2009 for pancreatic cancer. The corresponding figures for biliary tract cancer were 60% and 37%. This decline in concordance was also observed with increasing age, e.g. the concordance between CR and PR for pancreatic cancer declined from 62% in patients<60 years to 36% among patients≥80 years. The corresponding figures for biliary tract cancer were 52% and 38%. CONCLUSION: There is an overwhelming underreporting of pancreatic and biliary tract cancers within the Swedish Cancer Register, which has increased during recent years. The reported decreasing incidence rates for pancreatic and biliary tract cancers might therefore be incorrect. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental misdiagnosed intrahepatic cholangiocarcinoma patients undergoing liver transplantation nationwide study japan background intrahepatic cholangiocarcinoma icc thought contraindication liver transplantation lt due poorer outcome meanwhile incidental misdiagnosed icc iicc infrequently reported although favorable outcome patients early icc undergoing lt reported recently incidence iicc outcome lt still unclear eastern asia method conducted nationwide survey analyze incidence iicc outcome lt japan results january 2001 december 2015 total 6997 lt performed japan among 18 cases 0 26 iicc reported 11 transplant centers five cases misdiagnosed hcc preoperatively median tumor size explanted liver 2 8 1 5 4 5 cm number tumor 1 1 7 well differentiated tumors found 7 cases recurrence lt found 10 patients 56 common site recurrence extrahepatic 90 recurrence free survival rates 1 3 5 years 83 3 65 5 45 8 respectively overall survival rates 1 3 5 years 77 8 61 1 42 8 respectively comparing national data japan results inferior patients hcc underwent lt 84 8 70 5 54 7 respectively unlike previous reports western countries single tumors 2 cm smaller well differentiated lesions lack microvascular invasions associated better os rfs conclusion though outcome lt patients iicc poorer patients hcc japan 3 year os still higher 60 results present study provide encouraging information patients diagnosed iicc lt google scholar","probabilities":0.9799733,"Title":"Incidental/Misdiagnosed Intrahepatic Cholangiocarcinoma In Patients Undergoing Liver Transplantation: Nationwide Study In Japan","Abstract":"Background: Intrahepatic cholangiocarcinoma (ICC) had been\nthought to be contraindication for liver transplantation (LT) due to\npoorer outcome. In the meanwhile, incidental/misdiagnosed ICC\n(iICC) are infrequently reported. Although, the favorable outcome of\npatients with early ICC undergoing LT have been reported recently,\nthe incidence of iICC and the outcome after LT is still unclear in\neastern Asia.\nMethod: We conducted nationwide survey to analyze the incidence\nof iICC and outcome after LT in Japan.\nResults: Between January 2001 and December 2015, a total of\n6997 LT was performed in Japan. Among them, 18 cases (0.26%)\nof iICC were reported from 11 transplant centers. Five cases were\nmisdiagnosed as HCC preoperatively. The median tumor size in\nexplanted liver was 2.8 [1.5-4.5] cm and the number of tumor was 1\n[1-7]. Well differentiated tumors were found in 7 cases. Recurrence\nafter LT was found in 10 patients (56%). The most common site for\nrecurrence was extrahepatic (90%). The recurrence-free survival\nrates at 1, 3, 5 years were 83.3%, 65.5%, 45.8%, respectively. The\noverall survival rates at 1, 3, and 5 years were 77.8%, 61.1%, and 42.8%,\nrespectively. Comparing with the national data in Japan, the results\nwere inferior to that of patients with HCC who underwent LT (84.8%,\n70.5%, and 54.7%, respectively). Unlike with previous reports from\nwestern countries, single tumors 2 cm or smaller, well differentiated\nlesions, and lack of microvascular invasions were not associated\nwith better OS and RFS.\nConclusion: Though the outcome of LT in patients with iICC was\npoorer than that of patients with HCC in Japan, 3-year OS was\nstill higher than 60%. The results of the present study will provide\nencouraging information to patients who were diagnosed as iICC\nafter LT.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidental/Misdiagnosed Intrahepatic Cholangiocarcinoma In Patients Undergoing Liver Transplantation: Nationwide Study In Japan Background: Intrahepatic cholangiocarcinoma (ICC) had been\nthought to be contraindication for liver transplantation (LT) due to\npoorer outcome. In the meanwhile, incidental/misdiagnosed ICC\n(iICC) are infrequently reported. Although, the favorable outcome of\npatients with early ICC undergoing LT have been reported recently,\nthe incidence of iICC and the outcome after LT is still unclear in\neastern Asia.\nMethod: We conducted nationwide survey to analyze the incidence\nof iICC and outcome after LT in Japan.\nResults: Between January 2001 and December 2015, a total of\n6997 LT was performed in Japan. Among them, 18 cases (0.26%)\nof iICC were reported from 11 transplant centers. Five cases were\nmisdiagnosed as HCC preoperatively. The median tumor size in\nexplanted liver was 2.8 [1.5-4.5] cm and the number of tumor was 1\n[1-7]. Well differentiated tumors were found in 7 cases. Recurrence\nafter LT was found in 10 patients (56%). The most common site for\nrecurrence was extrahepatic (90%). The recurrence-free survival\nrates at 1, 3, 5 years were 83.3%, 65.5%, 45.8%, respectively. The\noverall survival rates at 1, 3, and 5 years were 77.8%, 61.1%, and 42.8%,\nrespectively. Comparing with the national data in Japan, the results\nwere inferior to that of patients with HCC who underwent LT (84.8%,\n70.5%, and 54.7%, respectively). Unlike with previous reports from\nwestern countries, single tumors 2 cm or smaller, well differentiated\nlesions, and lack of microvascular invasions were not associated\nwith better OS and RFS.\nConclusion: Though the outcome of LT in patients with iICC was\npoorer than that of patients with HCC in Japan, 3-year OS was\nstill higher than 60%. The results of the present study will provide\nencouraging information to patients who were diagnosed as iICC\nafter LT. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"simple scoring system predict early recurrence bismuth corlette type iv perihilar cholangiocarcinoma background early recurrence reported predictive poor prognosis patients perihilar cholangiocarcinoma pcca resection objective study construct useful scoring system predict early recurrence bismuth corlette type iv pcca patients clinic investigate value early recurrence directing post operative surveillance adjuvant therapy methods total 244 patients underwent radical resection type iv pcca included data clinicopathological characteristics perioperative details survival outcomes analyzed survival curves generated using kaplan meier method univariate multivariate logistic regression models used identify factors associated early recurrence results twenty one months defined cutoff point distinguish early late recurrence univariate multivariate analysis revealed ca19 9 level 200 u ml r1 resection margin higher n category positive lymphovascular invasion independent predictors early recurrence scoring system constructed accordingly early recurrence rates patients scores 0 1 2 3 4 5 23 9 38 7 60 0 78 6 83 4 100 respectively adjuvant therapy significantly associated higher overall survival rate patients early recurrence late recurrence patients early recurrence group scores 2 better prognoses adjuvant therapy conclusions simple scoring system using ca19 9 level n category resection margin lymphovascular invasion status predict early recurrence thus might direct post operative surveillance adjuvant therapy patients type iv pcca stn","probabilities":0.9799733,"Title":"A Simple Scoring System To Predict Early Recurrence Of Bismuth-Corlette Type Iv Perihilar Cholangiocarcinoma","Abstract":"Background: Early recurrence has been reported to be predictive of a poor prognosis for patients with perihilar cholangiocarcinoma (pCCA) after resection. The objective of our study was to construct a useful scoring system to predict early recurrence for Bismuth-Corlette type IV pCCA patients in clinic and to investigate the value of early recurrence in directing post-operative surveillance and adjuvant therapy. \r\n\r\n Methods: In total, 244 patients who underwent radical resection for type IV pCCA were included. Data on clinicopathological characteristics, perioperative details and survival outcomes were analyzed. Survival curves were generated using the Kaplan-Meier method. Univariate and multivariate logistic-regression models were used to identify factors associated with early recurrence. \r\n\r\n Results: Twenty-one months was defined as the cutoff point to distinguish between early and late recurrence. Univariate and multivariate analysis revealed that CA19-9 level >200 U/mL, R1 resection margin, higher N category and positive lymphovascular invasion were independent predictors of early recurrence. The scoring system was constructed accordingly. The early-recurrence rates of patients with scores of 0, 1, 2, 3, 4, and 5 were 23.9%, 38.7%, 60.0%, 78.6%, 83.4%, and 100%, respectively. Adjuvant therapy was significantly associated with higher overall survival rate for patients with early recurrence, but not for those with late recurrence. Patients in the early-recurrence group with scores ≥2 had better prognoses after adjuvant therapy. \r\n\r\n Conclusions: A simple scoring system using CA19-9 level, N category, resection margin and lymphovascular invasion status could predict early recurrence, and thus might direct post-operative surveillance and adjuvant therapy for patients with type IV pCCA.","Source":"STN","category":"HUMAN","training_data":"A Simple Scoring System To Predict Early Recurrence Of Bismuth-Corlette Type Iv Perihilar Cholangiocarcinoma Background: Early recurrence has been reported to be predictive of a poor prognosis for patients with perihilar cholangiocarcinoma (pCCA) after resection. The objective of our study was to construct a useful scoring system to predict early recurrence for Bismuth-Corlette type IV pCCA patients in clinic and to investigate the value of early recurrence in directing post-operative surveillance and adjuvant therapy. \r\n\r\n Methods: In total, 244 patients who underwent radical resection for type IV pCCA were included. Data on clinicopathological characteristics, perioperative details and survival outcomes were analyzed. Survival curves were generated using the Kaplan-Meier method. Univariate and multivariate logistic-regression models were used to identify factors associated with early recurrence. \r\n\r\n Results: Twenty-one months was defined as the cutoff point to distinguish between early and late recurrence. Univariate and multivariate analysis revealed that CA19-9 level >200 U/mL, R1 resection margin, higher N category and positive lymphovascular invasion were independent predictors of early recurrence. The scoring system was constructed accordingly. The early-recurrence rates of patients with scores of 0, 1, 2, 3, 4, and 5 were 23.9%, 38.7%, 60.0%, 78.6%, 83.4%, and 100%, respectively. Adjuvant therapy was significantly associated with higher overall survival rate for patients with early recurrence, but not for those with late recurrence. Patients in the early-recurrence group with scores ≥2 had better prognoses after adjuvant therapy. \r\n\r\n Conclusions: A simple scoring system using CA19-9 level, N category, resection margin and lymphovascular invasion status could predict early recurrence, and thus might direct post-operative surveillance and adjuvant therapy for patients with type IV pCCA. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors patients cholangiocellular carcinoma comprehensive analysis 570 patients background aims patients cholangiocellular carcinoma ccc poor survival due small patient numbers randomized prospective studies exist aim study characterize patients characteristics evaluate treatments nd prognostic factors patients ccc methods collected data patients ccc treated institution 2000 2010 analyzed clinicopathological characteristics results 570 patients ccc identi ed classi ed intrahepatic ccc extrahepatic ccc ampullary carcinoma ac gallbladder carcinoma mixed ccc hcc 39 patients diagnosed uicc stage iv 10 primary sclerosing cholangitis psc associated difference median overall survival os 46 underwent resection tumour resection os 25 months compared 9 3 months non resected patients p 0 0001 1 3 5 year survival 77 3 35 3 25 3 resected patients 43 3 10 2 2 1 non resected patients best surgical results achieved patients ac median survival 5 2 years adjuvant chemotherapy gemcitabine beni cial patients metastatic disease non resectable tumours signi cantly longer survival treated chemotherapy 15 8 vs 1 8 months median os p 0 0001 12 8 vs 2 3 months median os p 0 0001 patients received rst line n 115 second line n 43 third line n 39 chemotherapy os 8 4 17 0 30 months respectively incomplete tumour resection lymph node involvement metastatic disease low histological differentiation associated short os cholestasis anemia elevation tumour markers ca 19 9 cea indicative poor survival conclusions even radical resection prognosis ccc poor patients ac best outcome ccc evidence bene adjuvant chemotherapy identi ed tumour related characteristics laboratory values associated poor survival google scholar","probabilities":0.9799733,"Title":"Prognostic Factors In Patients With Cholangiocellular Carcinoma - Comprehensive Analysis Of 570 Patients","Abstract":"Background and Aims: Patients with cholangiocellular carcinoma (CCC) have very poor survival. Due to small patient numbers, only few randomized prospective studies exist. The aim of the study was to characterize patients’ characteristics, evaluate the treatments and find prognostic factors in patients with CCC. Methods: We collected data from all patients with CCC treated in our institution from 2000 to 2010 and analyzed their clinicopathological characteristics. Results: 570 patients with CCC were identified and classified into intrahepatic CCC, extrahepatic CCC, ampullary carcinoma (AC), gallbladder carcinoma or mixed CCC/HCC. 39% of all patients were diagnosed at UICC stage IV. 10% had primary sclerosing cholangitis (PSC), which was not associated with a difference in median overall survival (OS). 46% underwent resection. After tumour resection, OS was 25 months compared to 9.3 months in non-resected patients (p<0.0001). The 1, 3 and 5 year survival was 77±3%, 35±3% and 25±3% in resected patients, and 43±3%, 10±2% and 2±1% in non-resected patients. The best surgical results were achieved in patients with AC with a median survival of 5.2 years. Adjuvant chemotherapy with gemcitabine was not benificial. Patients with metastatic disease or non-resectable tumours had a significantly longer survival when treated with chemotherapy (15.8 vs. 1.8 months median OS, p<0.0001 and 12.8 vs. 2.3 months median OS, p<0.0001). Patients who received first line (N=115), second line (N=43) and third line (N=39) chemotherapy had an OS of 8.4, 17.0 and 30 months, respectively. Incomplete tumour resection, lymph node involvement, metastatic disease and low histological differentiation were associated with a short OS. Cholestasis, anemia and the elevation of the tumour markers CA 19–9 or CEA were indicative for a poor survival. Conclusions: Even after radical resection, prognosis of CCC is poor. Patients with AC have the best outcome of all CCC. There is no evidence for a benefit of adjuvant chemotherapy. We identified tumour-related characteristics and laboratory values which are associated with a poor survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Factors In Patients With Cholangiocellular Carcinoma - Comprehensive Analysis Of 570 Patients Background and Aims: Patients with cholangiocellular carcinoma (CCC) have very poor survival. Due to small patient numbers, only few randomized prospective studies exist. The aim of the study was to characterize patients’ characteristics, evaluate the treatments and find prognostic factors in patients with CCC. Methods: We collected data from all patients with CCC treated in our institution from 2000 to 2010 and analyzed their clinicopathological characteristics. Results: 570 patients with CCC were identified and classified into intrahepatic CCC, extrahepatic CCC, ampullary carcinoma (AC), gallbladder carcinoma or mixed CCC/HCC. 39% of all patients were diagnosed at UICC stage IV. 10% had primary sclerosing cholangitis (PSC), which was not associated with a difference in median overall survival (OS). 46% underwent resection. After tumour resection, OS was 25 months compared to 9.3 months in non-resected patients (p<0.0001). The 1, 3 and 5 year survival was 77±3%, 35±3% and 25±3% in resected patients, and 43±3%, 10±2% and 2±1% in non-resected patients. The best surgical results were achieved in patients with AC with a median survival of 5.2 years. Adjuvant chemotherapy with gemcitabine was not benificial. Patients with metastatic disease or non-resectable tumours had a significantly longer survival when treated with chemotherapy (15.8 vs. 1.8 months median OS, p<0.0001 and 12.8 vs. 2.3 months median OS, p<0.0001). Patients who received first line (N=115), second line (N=43) and third line (N=39) chemotherapy had an OS of 8.4, 17.0 and 30 months, respectively. Incomplete tumour resection, lymph node involvement, metastatic disease and low histological differentiation were associated with a short OS. Cholestasis, anemia and the elevation of the tumour markers CA 19–9 or CEA were indicative for a poor survival. Conclusions: Even after radical resection, prognosis of CCC is poor. Patients with AC have the best outcome of all CCC. There is no evidence for a benefit of adjuvant chemotherapy. We identified tumour-related characteristics and laboratory values which are associated with a poor survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"bactibilia women affected diseases biliary tract pancreas strobe guidelines adherent cross sectional study southern italy purpose bile hepatobiliary lipid rich sterile solution colonization microorganisms defines condition bactibilia study aimed assess bile microbiological flora potential link comorbidity women methodology performed microbiologic investigation 53 female patients biliopancreatic diseases granted consent analysed data using matlab platform results found frequent disease associated bactibilia pancreas head carcinoma phc p 0 0015 least frequent disease gall bladder carcinoma gbc p 0 0002 common microorganisms pseudomonas spp p 0 0001 escherichia coli p 0 0001 particular pseudomonas spp e coli negatively correlated phc presence positively correlated cca univariate multivariate analysis conclusions gram negative bacteria linked tumour associated inflammatory status last 30 years analysis mortality rate italy phc gbc shows increasing decreasing trend respectively although study targeted 53 patients reflect frequency diagnosis southern italian population decrease gbc may raise suggestion ofnon adherence mediterranean diet may become prevalent southern italy since 1990s pubmed","probabilities":0.9799733,"Title":"Bactibilia in women affected with diseases of the biliary tract and pancreas A STROBE guidelines-adherent cross-sectional study in Southern Italy","Abstract":"PURPOSE: Bile is a hepatobiliary lipid-rich sterile solution, and its colonization by microorganisms defines the condition of bactibilia. In this study, we aimed to assess the bile microbiological flora and its potential link with comorbidity in women. METHODOLOGY: We performed a microbiologic investigation on 53 female patients with biliopancreatic diseases who granted consent, and we analysed the data using a MATLAB platform. RESULTS: We found that the most frequent disease associated with bactibilia was pancreas head carcinoma (PHC) (P=0.0015), while the least frequent disease was gall bladder carcinoma (GBC) (P=0.0002). The most common microorganisms were Pseudomonas spp. (P<0.0001) and Escherichia coli (P<0.0001). In particular Pseudomonas spp. and E. coli were negatively correlated to PHC presence and positively correlated to CCA by both univariate and multivariate analysis. CONCLUSIONS: Gram-negative bacteria have been linked to a tumour-associated inflammatory status. In the last 30 years, the analysis of mortality rate in Italy for PHC and GBC shows an increasing and a decreasing trend, respectively. Although this study targeted only 53 patients and does not reflect the frequency of diagnosis in a Southern Italian population, the decrease in GBC may raise the suggestion ofnon-adherence to a Mediterranean diet that may have become more prevalent in Southern Italy since the 1990s.","Source":"PubMed","category":"HUMAN","training_data":"Bactibilia in women affected with diseases of the biliary tract and pancreas A STROBE guidelines-adherent cross-sectional study in Southern Italy PURPOSE: Bile is a hepatobiliary lipid-rich sterile solution, and its colonization by microorganisms defines the condition of bactibilia. In this study, we aimed to assess the bile microbiological flora and its potential link with comorbidity in women. METHODOLOGY: We performed a microbiologic investigation on 53 female patients with biliopancreatic diseases who granted consent, and we analysed the data using a MATLAB platform. RESULTS: We found that the most frequent disease associated with bactibilia was pancreas head carcinoma (PHC) (P=0.0015), while the least frequent disease was gall bladder carcinoma (GBC) (P=0.0002). The most common microorganisms were Pseudomonas spp. (P<0.0001) and Escherichia coli (P<0.0001). In particular Pseudomonas spp. and E. coli were negatively correlated to PHC presence and positively correlated to CCA by both univariate and multivariate analysis. CONCLUSIONS: Gram-negative bacteria have been linked to a tumour-associated inflammatory status. In the last 30 years, the analysis of mortality rate in Italy for PHC and GBC shows an increasing and a decreasing trend, respectively. Although this study targeted only 53 patients and does not reflect the frequency of diagnosis in a Southern Italian population, the decrease in GBC may raise the suggestion ofnon-adherence to a Mediterranean diet that may have become more prevalent in Southern Italy since the 1990s. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gall bladder cancers truly incidental aim seek analyze features suggestive gallbladder cancer gbc preoperative imaging intraoperative findings patients diagnosed incidental gbc igbc methods study conducted 79 patients igbc managed department 10 year period 2003 2012 review preoperative imaging operative notes done ascertain suspicion malignancy retrospect results 79 patients ultrasound abdomen showed diffuse thickening suspicious malignancy 5 patients diffuse suspicious thickening seen 4 patients focal thickening suspicious malignancy present 24 patients preoperative computed tomography magnetic resonance imaging done 9 patients suspicion malignancy 5 patients difficult cholecystectomy encountered due dense inflammatory adhesions intraoperative findings showed focal thickening gallbladder gallbladder mass 9 17 patients respectively overall analysis 37 patients preoperative imaging intraoperative findings suggestive malignancy either missed gbc unsuspected unexpected gbc 42 53 2 patients evidence suggestive malignancy unanticipated diagnosis conclusion study highlights potential rare pitfall laparoscopic cholecystectomy greater awareness clinical entity along high index suspicion low threshold conversion open procedure especially endemic areas may avert avoidable patient morbidity mortality stn","probabilities":0.9799733,"Title":"Incidental Gall Bladder Cancers: Are They Truly Incidental?","Abstract":"Aim: To seek and analyze features suggestive of gallbladder cancer (GBC) on preoperative imaging and intraoperative findings in patients diagnosed as having incidental GBC (IGBC). \r\n\r\n Methods: The study was conducted on 79 patients of IGBC managed in our department over a 10-year period (2003-2012). Review of preoperative imaging and operative notes was done to ascertain any suspicion of malignancy-in-retrospect. \r\n\r\n Results: Of the 79 patients, Ultrasound abdomen showed diffuse thickening, not suspicious of malignancy in 5 patients, and diffuse suspicious thickening was seen in 4 patients. Focal thickening suspicious of malignancy was present in 24 patients. Preoperative computed tomography/magnetic resonance imaging was done in 9 patients for suspicion of malignancy. In 5 patients, difficult Cholecystectomy was encountered due to dense/inflammatory adhesions. Intraoperative findings showed focal thickening of the gallbladder and a gallbladder mass in 9 and 17 patients respectively. On overall analysis, 37 patients had preoperative imaging or intraoperative findings suggestive of malignancy, which was either a missed GBC or an unsuspected/unexpected GBC. In 42 (53.2%) patients, there was no evidence suggestive of malignancy and was an unanticipated diagnosis. \r\n\r\n Conclusion: Our study highlights a potential and not-so-rare pitfall of Laparoscopic Cholecystectomy. A greater awareness of this clinical entity along with a high index of suspicion and a low threshold for conversion to open procedure, especially in endemic areas may avert avoidable patient morbidity and mortality.","Source":"STN","category":"HUMAN","training_data":"Incidental Gall Bladder Cancers: Are They Truly Incidental? Aim: To seek and analyze features suggestive of gallbladder cancer (GBC) on preoperative imaging and intraoperative findings in patients diagnosed as having incidental GBC (IGBC). \r\n\r\n Methods: The study was conducted on 79 patients of IGBC managed in our department over a 10-year period (2003-2012). Review of preoperative imaging and operative notes was done to ascertain any suspicion of malignancy-in-retrospect. \r\n\r\n Results: Of the 79 patients, Ultrasound abdomen showed diffuse thickening, not suspicious of malignancy in 5 patients, and diffuse suspicious thickening was seen in 4 patients. Focal thickening suspicious of malignancy was present in 24 patients. Preoperative computed tomography/magnetic resonance imaging was done in 9 patients for suspicion of malignancy. In 5 patients, difficult Cholecystectomy was encountered due to dense/inflammatory adhesions. Intraoperative findings showed focal thickening of the gallbladder and a gallbladder mass in 9 and 17 patients respectively. On overall analysis, 37 patients had preoperative imaging or intraoperative findings suggestive of malignancy, which was either a missed GBC or an unsuspected/unexpected GBC. In 42 (53.2%) patients, there was no evidence suggestive of malignancy and was an unanticipated diagnosis. \r\n\r\n Conclusion: Our study highlights a potential and not-so-rare pitfall of Laparoscopic Cholecystectomy. A greater awareness of this clinical entity along with a high index of suspicion and a low threshold for conversion to open procedure, especially in endemic areas may avert avoidable patient morbidity and mortality. STN","prediction_labels":"HUMAN"},{"cleaned":"secular trends incidence cholangiocarcinoma usa impact misclassification background aims reported incidence intrahepatic cholangiocarcinoma icc increased usa extrahepatic cholangiocarcinoma ecc decreased remained stable however neither recent trends effects misclassification klatskin tumors known methods using surveillance epidemiology end results program databases calculated average annual age adjusted incidence rates aa irs icc ecc 4 year time periods 1992 1995 1996 1999 2000 2003 2004 2007 aa irs calculated misclassified well correctly classified klatskin tumors aa irs also calculated based age sex race multivariable poisson regression models used evaluate secular trends icc ecc results aa ir icc 0 92 1992 1995 0 93 2004 2007 aa ir ecc increased 0 70 1992 1995 0 95 2004 2007 significant trend aa ir icc p 0 07 significant increase ecc across 4 year time periods p 0 001 klatskin tumors comprised 6 7 ccs approximately 90 45 misclassified icc 1992 2000 2001 2007 respectively adjusted poisson models showed significant differences temporal trend icc ecc due misclassification klatskin tumors conclusions incidence icc remained stable 1992 2007 slight fluctuations incidence ecc increasing misclassification klatskin tumors appear play significant role trends ccs stn","probabilities":0.9799733,"Title":"Secular Trends In The Incidence Of Cholangiocarcinoma In The Usa And The Impact Of Misclassification","Abstract":"Background and aims: It has been reported that the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the USA, while extrahepatic cholangiocarcinoma (ECC) has decreased or remained stable. However, neither the recent trends nor the effects of the misclassification of Klatskin tumors are known. \r\n\r\n Methods: Using the Surveillance, Epidemiology, and End Results program databases, we calculated the average annual age-adjusted incidence rates (AA-IRs) of ICC and ECC in 4-year time periods (1992-1995, 1996-1999, 2000-2003, 2004-2007). These AA-IRs were calculated with misclassified as well as correctly classified Klatskin tumors. AA-IRs were also calculated based on age, sex, and race. Multivariable Poisson regression models were used to evaluate the secular trends of ICC and ECC. \r\n\r\n Results: The AA-IR of ICC was 0.92 in 1992-1995 and 0.93 in 2004-2007, while the AA-IR of ECC increased from 0.70 in 1992-1995 to 0.95 in 2004-2007. There was no significant trend in AA-IR of ICC (p = 0.07), while there was a significant increase in ECC across the 4-year time periods (p < 0.001). Klatskin tumors comprised 6.7% of CCs with approximately 90 and 45% misclassified as ICC during 1992-2000 and 2001-2007, respectively. Adjusted Poisson models showed no significant differences in the temporal trend of ICC or ECC due to misclassification of Klatskin tumors. \r\n\r\n Conclusions: The incidence of ICC has remained stable between 1992 and 2007 with only slight fluctuations, while the incidence of ECC has been increasing. Misclassification of Klatskin tumors does not appear to play a significant role in the trends of CCs.","Source":"STN","category":"HUMAN","training_data":"Secular Trends In The Incidence Of Cholangiocarcinoma In The Usa And The Impact Of Misclassification Background and aims: It has been reported that the incidence of intrahepatic cholangiocarcinoma (ICC) has increased in the USA, while extrahepatic cholangiocarcinoma (ECC) has decreased or remained stable. However, neither the recent trends nor the effects of the misclassification of Klatskin tumors are known. \r\n\r\n Methods: Using the Surveillance, Epidemiology, and End Results program databases, we calculated the average annual age-adjusted incidence rates (AA-IRs) of ICC and ECC in 4-year time periods (1992-1995, 1996-1999, 2000-2003, 2004-2007). These AA-IRs were calculated with misclassified as well as correctly classified Klatskin tumors. AA-IRs were also calculated based on age, sex, and race. Multivariable Poisson regression models were used to evaluate the secular trends of ICC and ECC. \r\n\r\n Results: The AA-IR of ICC was 0.92 in 1992-1995 and 0.93 in 2004-2007, while the AA-IR of ECC increased from 0.70 in 1992-1995 to 0.95 in 2004-2007. There was no significant trend in AA-IR of ICC (p = 0.07), while there was a significant increase in ECC across the 4-year time periods (p < 0.001). Klatskin tumors comprised 6.7% of CCs with approximately 90 and 45% misclassified as ICC during 1992-2000 and 2001-2007, respectively. Adjusted Poisson models showed no significant differences in the temporal trend of ICC or ECC due to misclassification of Klatskin tumors. \r\n\r\n Conclusions: The incidence of ICC has remained stable between 1992 and 2007 with only slight fluctuations, while the incidence of ECC has been increasing. Misclassification of Klatskin tumors does not appear to play a significant role in the trends of CCs. STN","prediction_labels":"HUMAN"},{"cleaned":"analysis long term survival 235 patients resectable unresectable hilar cholangiocarcinoma introduction radical resection remains curative treatment hilar cholangiocarcinoma hcca limited proportion patients however eligible resection unresectable patients generally undergo palliative biliary drainage survival prognostic factors patients largely unknown aim evaluate survival denominator patients presenting hcca defi ne prognostic factors methods denominator hcca patients seen center march 2003 march 2009 identifi ed demographics treatment pathology results survival analyzed results 235 patients suspected hcca identifi ed 109 patients 46 underwent laparotomy 71 65 patients resection performed overall median 5 year survival resected patients 39 months 44 respectively compared 13 months 6 unresectable patients survival better unresectable patients undergone explorative laparotomy 16 vs 10 months p 0 02 unresectable patients best median survival found patients locally advanced disease 16 months worst median survival patients liver metastasis 4 months p 0 001 164 unresectable patients 16 10 survived longer 3 years pathological confi rmation malignancy available 9 56 patients conclusion 235 patients referred center resection performed 71 patients 30 median survival 39 months prognosis unresectable patients poor especially patients liver metastasis yet longterm survival still found 10 patients undergoing palliative biliary drainage google scholar","probabilities":0.9799733,"Title":"Analysis Of Long-Term Survival In 235 Patients With Resectable And Unresectable Hilar Cholangiocarcinoma","Abstract":"Introduction: Radical resection remains the only curative\ntreatment for hilar cholangiocarcinoma (HCCA). Only a\nlimited proportion of patients is however eligible for resection.\nUnresectable patients generally undergo palliative\nbiliary drainage. The survival and prognostic factors of these\npatients are largely unknown.\nAim: To evaluate survival in the denominator of patients\npresenting with HCCA and to defi ne prognostic factors.\nMethods: The denominator of HCCA patients seen in our\ncenter between March 2003 and March 2009 were identifi ed.\nDemographics, treatment, pathology results and survival\nwere analyzed.\nResults: 235 patients with suspected HCCA were identifi ed.\n109 Patients (46%) underwent laparotomy, and in 71 (65%)\nof these patients resection was performed. Overall median\nand 5-year survival of resected patients were 39 months and\n44%, respectively, as compared to 13 months and 6%, in\nunresectable patients. Survival was better in unresectable\npatients who had undergone explorative laparotomy (16 vs\n10 months, p = 0.02). In unresectable patients, best median\nsurvival was found in patients with locally advanced disease\n(16 months) and worst median survival in patients with liver\nmetastasis (4 months, p < 0.001). Of 164 unresectable\npatients, 16 (10%) survived longer than 3 years. Pathological\nconfi rmation of malignancy was available in 9 (56%) of\nthese patients.\nConclusion: Of all 235 patients referred to our center, a\nresection was performed in 71 patients (30%) with a median\nsurvival of 39 months. Prognosis for unresectable patients is\npoor, especially for patients with liver metastasis. Yet, longterm\nsurvival was still found in 10% of patients undergoing\npalliative biliary drainage.","Source":"Google Scholar","category":"HUMAN","training_data":"Analysis Of Long-Term Survival In 235 Patients With Resectable And Unresectable Hilar Cholangiocarcinoma Introduction: Radical resection remains the only curative\ntreatment for hilar cholangiocarcinoma (HCCA). Only a\nlimited proportion of patients is however eligible for resection.\nUnresectable patients generally undergo palliative\nbiliary drainage. The survival and prognostic factors of these\npatients are largely unknown.\nAim: To evaluate survival in the denominator of patients\npresenting with HCCA and to defi ne prognostic factors.\nMethods: The denominator of HCCA patients seen in our\ncenter between March 2003 and March 2009 were identifi ed.\nDemographics, treatment, pathology results and survival\nwere analyzed.\nResults: 235 patients with suspected HCCA were identifi ed.\n109 Patients (46%) underwent laparotomy, and in 71 (65%)\nof these patients resection was performed. Overall median\nand 5-year survival of resected patients were 39 months and\n44%, respectively, as compared to 13 months and 6%, in\nunresectable patients. Survival was better in unresectable\npatients who had undergone explorative laparotomy (16 vs\n10 months, p = 0.02). In unresectable patients, best median\nsurvival was found in patients with locally advanced disease\n(16 months) and worst median survival in patients with liver\nmetastasis (4 months, p < 0.001). Of 164 unresectable\npatients, 16 (10%) survived longer than 3 years. Pathological\nconfi rmation of malignancy was available in 9 (56%) of\nthese patients.\nConclusion: Of all 235 patients referred to our center, a\nresection was performed in 71 patients (30%) with a median\nsurvival of 39 months. Prognosis for unresectable patients is\npoor, especially for patients with liver metastasis. Yet, longterm\nsurvival was still found in 10% of patients undergoing\npalliative biliary drainage. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"high expression telomerase independent prognostic factor ampullary carcinoma background telomerase activity human telomerase reverse transcriptase tert reported markers tumor aggressiveness poor prognosis several digestive cancers present study examined telomerase activity tert expression ampullary carcinoma determine whether parameters used indicators aggressiveness prognosis methods telomerase activity analyzed using telomeric repeat amplification protocol assay tert examined immunohistochemistry ampullary carcinoma tissue samples resected 46 patients results telomerase activity detected 42 91 3 ampullary carcinomas 27 58 7 showed high activity whereas tert expression detected 35 76 1 including 21 weak expression 14 strong expression univariate analysis revealed histological grade p 0 029 tumor depth p 0 001 nodal status p 0 013 uicc stage p 0 009 perineural invasion p 0 001 telomerase activity p 0 031 significantly associated disease specific survival multivariate analysis telomerase activity remained independent predictor prognosis p 0 043 statistical significance survival among three grades tert expression p 0 054 however subgroup analysis patients strong tert expression showed significantly poorer prognosis without tert expression p 0 013 conclusions results suggest high telomerase activity strong tert expression may serve new prognostic markers evaluating prognosis patients resected ampullary carcinoma stn","probabilities":1.0,"Title":"High Expression Of Telomerase Is An Independent Prognostic Factor In Ampullary Carcinoma","Abstract":"Background: Telomerase activity and human telomerase reverse transcriptase (TERT) have been reported as markers of tumor aggressiveness and poor prognosis in several digestive cancers. In the present study, we examined telomerase activity and TERT expression in ampullary carcinoma to determine whether these parameters could be used as indicators of aggressiveness and prognosis. \r\n\r\n Methods: Telomerase activity was analyzed by using the telomeric repeat amplification protocol assay, and TERT was examined by immunohistochemistry in ampullary carcinoma tissue samples resected from 46 patients. \r\n\r\n Results: Telomerase activity was detected in 42 (91.3%) ampullary carcinomas and 27 (58.7%) showed high activity, whereas TERT expression was detected in 35 (76.1%), including 21 with weak expression and 14 with strong expression. Univariate analysis revealed that histological grade (P = 0.029), tumor depth (P < 0.001), nodal status (P = 0.013), UICC stage (P = 0.009), perineural invasion (P < 0.001), and telomerase activity (P = 0.031) were significantly associated with disease-specific survival. In multivariate analysis, only telomerase activity remained an independent predictor of prognosis (P = 0.043). There was no statistical significance for survival among the three grades of TERT expression (P = 0.054); however, in subgroup analysis, patients with strong TERT expression showed significantly poorer prognosis than those without TERT expression (P = 0.013). \r\n\r\n Conclusions: Our results suggest that high telomerase activity and strong TERT expression may serve as new prognostic markers for evaluating the prognosis of patients with resected ampullary carcinoma.","Source":"STN","category":"ANIMAL","training_data":"High Expression Of Telomerase Is An Independent Prognostic Factor In Ampullary Carcinoma Background: Telomerase activity and human telomerase reverse transcriptase (TERT) have been reported as markers of tumor aggressiveness and poor prognosis in several digestive cancers. In the present study, we examined telomerase activity and TERT expression in ampullary carcinoma to determine whether these parameters could be used as indicators of aggressiveness and prognosis. \r\n\r\n Methods: Telomerase activity was analyzed by using the telomeric repeat amplification protocol assay, and TERT was examined by immunohistochemistry in ampullary carcinoma tissue samples resected from 46 patients. \r\n\r\n Results: Telomerase activity was detected in 42 (91.3%) ampullary carcinomas and 27 (58.7%) showed high activity, whereas TERT expression was detected in 35 (76.1%), including 21 with weak expression and 14 with strong expression. Univariate analysis revealed that histological grade (P = 0.029), tumor depth (P < 0.001), nodal status (P = 0.013), UICC stage (P = 0.009), perineural invasion (P < 0.001), and telomerase activity (P = 0.031) were significantly associated with disease-specific survival. In multivariate analysis, only telomerase activity remained an independent predictor of prognosis (P = 0.043). There was no statistical significance for survival among the three grades of TERT expression (P = 0.054); however, in subgroup analysis, patients with strong TERT expression showed significantly poorer prognosis than those without TERT expression (P = 0.013). \r\n\r\n Conclusions: Our results suggest that high telomerase activity and strong TERT expression may serve as new prognostic markers for evaluating the prognosis of patients with resected ampullary carcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic factors adjuvant treatments surgically treated cancers biliary tract multicentre study anatolian society medical oncology asmo background biliary tract cancers rare surgical resection standard treatment early stages however reports benefits adjuvant treatment following surgical resection conflicting study aimed evaluate factors affecting survival adjuvant treatments patients surgically treated biliary tract cancers materials methods patient clinical features adjuvant treatments efficacy prognostic factor data evaluated survival analyses performed using spss 15 0 results median overall survival 30 7 months 95 confidence interval ci 18 4 42 9 months median survival 19 months 95 ci 6 33 patients treated fluorouracil based chemotherapy 53 months 95 ci 33 2 78 8 gemcitabine based chemotherapy p 0 033 univariate analysis poor prognostic factors survival galbladder localization perineural invasion hepatic invasion lack adjuvant chemoradiotherapy treatment lack lymph node dissection multivariate analysis perineural invasion poor prognostic factor p 0 008 conclusions biliary tract cancers generally poor prognoses main factors affecting survival tumour localization perineural invasion hepatic invasion adjuvant chemoradiotherapy lymph node dissection gemcitabine based adjuvant chemotherapy effective 5 fluorouracil based chemotherapy pubmed","probabilities":0.9799733,"Title":"Prognostic factors and adjuvant treatments for surgically treated cancers of the biliary tract: a multicentre study of the Anatolian Society of Medical Oncology (ASMO)","Abstract":"BACKGROUND: Biliary tract cancers are rare, and surgical resection is the standard treatment at early stages. However, reports on the benefits of adjuvant treatment following surgical resection are conflicting. This study aimed to evaluate the factors affecting survival and adjuvant treatments in patients with surgically treated biliary tract cancers. MATERIALS AND METHODS: Patient clinical features, adjuvant treatments, and efficacy and prognostic factor data were evaluated. Survival analyses were performed using SPSS 15.0. RESULTS: The median overall survival was 30.7 months (95% confidence interval [CI], 18.4-42.9 months). Median survival was 19 months (95% CI, 6-33) for patients treated with fluorouracil based chemotherapy and 53 months (95% CI, 33.2-78.8) with gemcitabine based chemotherapy (p=0.033). On univariate analysis, poor prognostic factors for survival were galbladder localization, perineural invasion, hepatic invasion, a lack of adjuvant chemoradiotherapy treatment, and a lack of lymph node dissection. On multivariate analysis, perineural invasion was a poor prognostic factor (p=0.008). CONCLUSIONS: Biliary tract cancers generally have poor prognoses. The main factors affecting survival are tumour localization, perineural invasion, hepatic invasion, adjuvant chemoradiotherapy, and lymph node dissection. Gemcitabine-based adjuvant chemotherapy is more effective than 5-fluorouracil-based chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors and adjuvant treatments for surgically treated cancers of the biliary tract: a multicentre study of the Anatolian Society of Medical Oncology (ASMO) BACKGROUND: Biliary tract cancers are rare, and surgical resection is the standard treatment at early stages. However, reports on the benefits of adjuvant treatment following surgical resection are conflicting. This study aimed to evaluate the factors affecting survival and adjuvant treatments in patients with surgically treated biliary tract cancers. MATERIALS AND METHODS: Patient clinical features, adjuvant treatments, and efficacy and prognostic factor data were evaluated. Survival analyses were performed using SPSS 15.0. RESULTS: The median overall survival was 30.7 months (95% confidence interval [CI], 18.4-42.9 months). Median survival was 19 months (95% CI, 6-33) for patients treated with fluorouracil based chemotherapy and 53 months (95% CI, 33.2-78.8) with gemcitabine based chemotherapy (p=0.033). On univariate analysis, poor prognostic factors for survival were galbladder localization, perineural invasion, hepatic invasion, a lack of adjuvant chemoradiotherapy treatment, and a lack of lymph node dissection. On multivariate analysis, perineural invasion was a poor prognostic factor (p=0.008). CONCLUSIONS: Biliary tract cancers generally have poor prognoses. The main factors affecting survival are tumour localization, perineural invasion, hepatic invasion, adjuvant chemoradiotherapy, and lymph node dissection. Gemcitabine-based adjuvant chemotherapy is more effective than 5-fluorouracil-based chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radiotherapy treatment patients unresectable extrahepatic cholangiocarcinoma purpose extrahepatic cholangiocarcinoma uncommon lethal malignancy analyzed role definitive chemoradiotherapy patients nonmetastatic locally advanced extrahepatic cholangiocarcinoma treated single institution methods materials retrospective analysis included 37 patients underwent external beam radiation therapy ebrt concurrent chemotherapy brachytherapy bt locally advanced extrahepatic cholangiocarcinoma local control lc overall survival os assessed univariate regression analysis used evaluate effects patient treatment related factors clinical outcomes results twenty three patients received ebrt alone 8 patients received ebrt plus bt 6 patients received bt alone median follow 14 months two patients alive without evidence recurrence time analysis actuarial os lc rates 1 year 59 90 respectively 22 71 respectively 2 years two patients lived beyond 5 years without evidence recurrence univariate analysis ebrt without bt improved lc compared bt alone 97 vs 56 1 year 75 vs 56 2 years p 0 096 patients received ebrt alone vs bt alone also improved lc 96 vs 56 1 year 80 vs 56 2 years p 0 113 age gender tumor location proximal vs distal histologic differentiation ebrt dose 50 gy ebrt planning method two dimensional vs three dimensional chemotherapy associated patient outcomes conclusions patients locally advanced extrahepatic cholangiocarcinoma poor survival long term survival rare majority patients treated ebrt local control time death suggesting symptoms due local tumor effect might effectively controlled radiation therapy ebrt important element treatment novel treatment approaches indicated therapy disease pubmed","probabilities":0.9799733,"Title":"Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma","Abstract":"PURPOSE: Extrahepatic cholangiocarcinoma is an uncommon but lethal malignancy. We analyzed the role of definitive chemoradiotherapy for patients with nonmetastatic, locally advanced extrahepatic cholangiocarcinoma treated at a single institution. METHODS AND MATERIALS: This retrospective analysis included 37 patients who underwent external beam radiation therapy (EBRT) with concurrent chemotherapy and/or brachytherapy (BT) for locally advanced extrahepatic cholangiocarcinoma. Local control (LC) and overall survival (OS) were assessed, and univariate regression analysis was used to evaluate the effects of patient- and treatment-related factors on clinical outcomes. RESULTS: Twenty-three patients received EBRT alone, 8 patients received EBRT plus BT, and 6 patients received BT alone (median follow-up of 14 months). Two patients were alive without evidence of recurrence at the time of analysis. Actuarial OS and LC rates at 1 year were 59% and 90%, respectively, and 22% and 71%, respectively, at 2 years. Two patients lived beyond 5 years without evidence of recurrence. On univariate analysis, EBRT with or without BT improved LC compared to BT alone (97% vs. 56% at 1 year; 75% vs. 56% at 2 years; p = 0.096). Patients who received EBRT alone vs. BT alone also had improved LC (96% vs. 56% at 1 year; 80% vs. 56% at 2 years; p = 0.113). Age, gender, tumor location (proximal vs. distal), histologic differentiation, EBRT dose (≤ or >50 Gy), EBRT planning method (two-dimensional vs. three-dimensional), and chemotherapy were not associated with patient outcomes. CONCLUSIONS: Patients with locally advanced extrahepatic cholangiocarcinoma have poor survival. Long-term survival is rare. The majority of patients treated with EBRT had local control at the time of death, suggesting that symptoms due to the local tumor effect might be effectively controlled with radiation therapy, and EBRT is an important element of treatment. Novel treatment approaches are indicated in the therapy for this disease.","Source":"PubMed","category":"HUMAN","training_data":"Radiotherapy in the treatment of patients with unresectable extrahepatic cholangiocarcinoma PURPOSE: Extrahepatic cholangiocarcinoma is an uncommon but lethal malignancy. We analyzed the role of definitive chemoradiotherapy for patients with nonmetastatic, locally advanced extrahepatic cholangiocarcinoma treated at a single institution. METHODS AND MATERIALS: This retrospective analysis included 37 patients who underwent external beam radiation therapy (EBRT) with concurrent chemotherapy and/or brachytherapy (BT) for locally advanced extrahepatic cholangiocarcinoma. Local control (LC) and overall survival (OS) were assessed, and univariate regression analysis was used to evaluate the effects of patient- and treatment-related factors on clinical outcomes. RESULTS: Twenty-three patients received EBRT alone, 8 patients received EBRT plus BT, and 6 patients received BT alone (median follow-up of 14 months). Two patients were alive without evidence of recurrence at the time of analysis. Actuarial OS and LC rates at 1 year were 59% and 90%, respectively, and 22% and 71%, respectively, at 2 years. Two patients lived beyond 5 years without evidence of recurrence. On univariate analysis, EBRT with or without BT improved LC compared to BT alone (97% vs. 56% at 1 year; 75% vs. 56% at 2 years; p = 0.096). Patients who received EBRT alone vs. BT alone also had improved LC (96% vs. 56% at 1 year; 80% vs. 56% at 2 years; p = 0.113). Age, gender, tumor location (proximal vs. distal), histologic differentiation, EBRT dose (≤ or >50 Gy), EBRT planning method (two-dimensional vs. three-dimensional), and chemotherapy were not associated with patient outcomes. CONCLUSIONS: Patients with locally advanced extrahepatic cholangiocarcinoma have poor survival. Long-term survival is rare. The majority of patients treated with EBRT had local control at the time of death, suggesting that symptoms due to the local tumor effect might be effectively controlled with radiation therapy, and EBRT is an important element of treatment. Novel treatment approaches are indicated in the therapy for this disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"endoscopic ampullectomy adenomatous ampullary tumor minimally invasive technique alternative surgery abstract available google scholar","probabilities":0.9799733,"Title":"Endoscopic Ampullectomy Of An Adenomatous Ampullary Tumor: A Minimally Invasive Technique As An Alternative To Surgery","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Endoscopic Ampullectomy Of An Adenomatous Ampullary Tumor: A Minimally Invasive Technique As An Alternative To Surgery Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"characteristics combined hepatocelluar cholangiocarcinoma comparison intrahepatic cholangiocarcinoma background 7th american joint committee cancer ajcc currently classifies combined hepatocellular cholangiocarcinoma chcc cc intrahepatic cholangiocarcinoma icc one category study outcomes comparing two carcinomas shown contrary results study designed compare survival prognostic factors carcinomas methods retrospectively reviewed medical records 107 patients chcc cc icc underwent liver resection january 2000 december 2009 results thirty patients 28 diagnosed chcc cc 77 patients 72 icc disease free survival dfs poorer chcc cc patients six months overall survival os durations similar p 0 477 chcc cc 58 months icc 45 months patients tumor size larger 5 cm vascular invasion lymph node ln metastasis prognostic factors patients however tumor size ln metastasis chcc cc patients carbohydrate antigen 19 9 differentiation ln metastasis icc patients found independent prognostic factors conclusions patients chcc cc showed poorer dfs similar os rates compared icc study revealed different prognostic factors chcc cc understand accurately chcc cc prognosis difference genetic characteristics tumor biology evaluated pubmed","probabilities":0.9799733,"Title":"Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: The 7th American Joint Committee on Cancer (AJCC) currently classifies combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) into one category. Study outcomes comparing the two carcinomas have shown contrary results. This study was designed to compare the survival and prognostic factors of both carcinomas. METHODS: We retrospectively reviewed the medical records of 107 patients with cHCC-CC or ICC who underwent liver resection between January 2000 and December 2009. RESULTS: Thirty patients (28%) were diagnosed with cHCC-CC, and 77 patients (72%) had ICC. Disease-free survival (DFS) was poorer in the cHCC-CC patients (six months), and the overall survival (OS) durations were similar (p = 0.477) between cHCC-CC (58 months) and ICC (45 months) patients. A tumor size larger than 5 cm, vascular invasion and lymph node (LN) metastasis were prognostic factors in all patients. However, tumor size and LN metastasis in cHCC-CC patients and carbohydrate antigen 19-9, differentiation and LN metastasis in ICC patients were found to be independent prognostic factors. CONCLUSIONS: Patients with cHCC-CC showed poorer DFS and similar OS rates compared to those with ICC. Our study revealed different prognostic factors in cHCC-CC. To understand more accurately cHCC-CC's prognosis, difference of genetic characteristics and tumor biology should be further evaluated.","Source":"PubMed","category":"HUMAN","training_data":"Characteristics of combined hepatocelluar-cholangiocarcinoma and comparison with intrahepatic cholangiocarcinoma BACKGROUND: The 7th American Joint Committee on Cancer (AJCC) currently classifies combined hepatocellular-cholangiocarcinoma (cHCC-CC) and intrahepatic cholangiocarcinoma (ICC) into one category. Study outcomes comparing the two carcinomas have shown contrary results. This study was designed to compare the survival and prognostic factors of both carcinomas. METHODS: We retrospectively reviewed the medical records of 107 patients with cHCC-CC or ICC who underwent liver resection between January 2000 and December 2009. RESULTS: Thirty patients (28%) were diagnosed with cHCC-CC, and 77 patients (72%) had ICC. Disease-free survival (DFS) was poorer in the cHCC-CC patients (six months), and the overall survival (OS) durations were similar (p = 0.477) between cHCC-CC (58 months) and ICC (45 months) patients. A tumor size larger than 5 cm, vascular invasion and lymph node (LN) metastasis were prognostic factors in all patients. However, tumor size and LN metastasis in cHCC-CC patients and carbohydrate antigen 19-9, differentiation and LN metastasis in ICC patients were found to be independent prognostic factors. CONCLUSIONS: Patients with cHCC-CC showed poorer DFS and similar OS rates compared to those with ICC. Our study revealed different prognostic factors in cHCC-CC. To understand more accurately cHCC-CC's prognosis, difference of genetic characteristics and tumor biology should be further evaluated. PubMed","prediction_labels":"HUMAN"},{"cleaned":"atp5b 2 microglobulin predictive markers prognosis patients gallbladder cancer differences clinical pathological biological characteristics adenocarcinoma ac squamous cell adenosquamous carcinoma sc asc gallbladder well documented study investigates clinical pathological associations atp5b 2m benign malignant lesions gallbladder study atp5b 2m expression 46 sc ascs 80 acs examined using immunohistochemistry rate atp5b positive expression significantly lower rate 2m expression significantly higher ac sc asc gallbladder adenomas gallbladder polyps gallbladder epithelium stone p 0 01 sc ascs larger tumor mass good differentiation compared acs positive 2m negative atp5b expression significantly associated large tumor size high tnm stage lymph node metastasis invasion sc ascs acs univariate kaplan meier analysis showed positive 2m p 0 05 p 0 001 expression negative atp5b p 0 001 expression significantly associated decreased overall survival sc asc ac patients multivariate cox regression analysis showed negative atp5b expression independent prognostic factor poor prognosis sc asc p 0 01 ac p 0 001 patients positive 2m expression independent prognostic factor poor prognosis ac p 0 05 patients study suggested positive 2m expression loss atp5b expression tumor tissues closely related metastasis invasion poor prognosis gallbladder cancer stn","probabilities":1.0,"Title":"Atp5B And ß2-Microglobulin Are Predictive Markers For The Prognosis Of Patients With Gallbladder Cancer","Abstract":"The differences in clinical, pathological, and biological characteristics between adenocarcinoma (AC) and squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder have not been well documented. This study investigates the clinical and pathological associations of ATP5B and β2M with benign and malignant lesions of the gallbladder. In this study, ATP5B and β2M expression in 46 SC/ASCs and 80 ACs were examined using immunohistochemistry. The rate of ATP5B positive expression was significantly lower, while the rate of β2M expression was significantly higher, in AC and SC/ASC than in gallbladder adenomas, gallbladder polyps, or gallbladder epithelium with stone (P < 0.01). More SC/ASCs had larger tumor mass and good differentiation compared to ACs. Positive β2M and negative ATP5B expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis, and invasion of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that positive β2M (P < 0.05 or P < 0.001) expression and negative ATP5B (P < 0.001) expression were significantly associated with decreased overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that negative ATP5B expression is an independent-prognostic factor for poor prognosis in both SC/ASC (P < 0.01) and AC (P < 0.001) patients. Positive β2M expression is an independent-prognostic factor for poor prognosis in AC (P < 0.05) patients. Our study suggested that positive β2M expression or loss of ATP5B expression in tumor tissues is closely related to the metastasis, invasion, and poor-prognosis of gallbladder cancer.","Source":"STN","category":"HUMAN","training_data":"Atp5B And ß2-Microglobulin Are Predictive Markers For The Prognosis Of Patients With Gallbladder Cancer The differences in clinical, pathological, and biological characteristics between adenocarcinoma (AC) and squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder have not been well documented. This study investigates the clinical and pathological associations of ATP5B and β2M with benign and malignant lesions of the gallbladder. In this study, ATP5B and β2M expression in 46 SC/ASCs and 80 ACs were examined using immunohistochemistry. The rate of ATP5B positive expression was significantly lower, while the rate of β2M expression was significantly higher, in AC and SC/ASC than in gallbladder adenomas, gallbladder polyps, or gallbladder epithelium with stone (P < 0.01). More SC/ASCs had larger tumor mass and good differentiation compared to ACs. Positive β2M and negative ATP5B expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis, and invasion of SC/ASCs and ACs. Univariate Kaplan-Meier analysis showed that positive β2M (P < 0.05 or P < 0.001) expression and negative ATP5B (P < 0.001) expression were significantly associated with decreased overall survival in both SC/ASC and AC patients. Multivariate Cox regression analysis showed that negative ATP5B expression is an independent-prognostic factor for poor prognosis in both SC/ASC (P < 0.01) and AC (P < 0.001) patients. Positive β2M expression is an independent-prognostic factor for poor prognosis in AC (P < 0.05) patients. Our study suggested that positive β2M expression or loss of ATP5B expression in tumor tissues is closely related to the metastasis, invasion, and poor-prognosis of gallbladder cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"extracorporeal shockwave lithotripsy eswl treatment gallbladder stones long term results 20 years aims aimed evaluate long term results extracorporeal shockwave lithotripsy eswl conservative treatment symptomatic gallbladder stones therapy used non invasive alternative surgery many european countries 1980 1990 experience years showed poor stone free rates frequent relapse symptoms introduction minimal invasive laparoscopic cholecystectomy replaced treatment worldwide first study examining results 20 years eswl methods retrospective study patients treated eswl uncomplicated symptomatic gallbladder stones institution 1989 1990 endpoints stone free recurrence rates symptomatic complicated gallbladder disease subsequent need surgical intervention well disease related mortality results march 1989 november 1990 160 patients treated total 217 eswl sessions exclusion 34 patients loss follow cohort comprised 126 patients mean follow 23 4 years 22 18 patients remained free symptoms gallstones initial treatment study period symptoms recurred mean 3 8 years 13 10 interventional treatment eswl ercp etc necessary subsequent cholecystectomy performed 91 72 patients mean 5 1 years last eswl three deaths 2 3 mortality related gallstone relapse occurred 1 gallbladder carcinoma 1 cholangio carcinoma 1 acute purulent cholecystitis conclusions long term results eswl unsatisfactory basis results eswl recommended treatment symptomatic cholecystolithiasis especially young patients indication eswl older patients 70 years well balanced risk developing gallbladder cancer stone related complications study serves critical reminder unforeseeable long term issues may arise newly introduced technique google scholar","probabilities":0.9799733,"Title":"Extracorporeal Shockwave Lithotripsy (Eswl) For The Treatment Of Gallbladder Stones: Long-Term Results After More Than 20 Years","Abstract":"Aims: We aimed to evaluate the long-term results of\nextracorporeal shockwave lithotripsy (ESWL) as a conservative treatment for symptomatic gallbladder stones.\nThis therapy was used as a non-invasive alternative to\nsurgery in many European countries in the 1980’s and\n1990’s, but experience after some years showed poor\nstone-free rates with frequent relapse of symptoms.\nIntroduction of minimal-invasive, laparoscopic cholecystectomy has replaced this treatment worldwide. This is the\nfirst study examining the results more than 20 years after\nESWL.\nMethods: Retrospective study on all patients treated with\nESWL for uncomplicated, symptomatic gallbladder stones\nat our institution between 1989 and 1990. The endpoints\nwere stone-free recurrence rates, symptomatic or complicated gallbladder disease and subsequent need for surgical\nintervention as well as disease-related mortality.\nResults: From March 1989 to November 1990 some 160\npatients were treated with a total of 217 ESWL sessions.\nAfter exclusion of 34 patients (loss of follow-up), the\ncohort comprised of 126 patients with a mean follow-up of\n23.4 years.\nOnly 22 (18%) patients remained free of symptoms and\ngallstones after the initial treatment during the study period.\nSymptoms recurred at a mean of 3.8 years, in 13 (10%)\nfurther interventional treatment (ESWL, ERCP, etc.) was\nnecessary. Subsequent cholecystectomy was performed in\n91 (72%) patients at a mean of 5.1 years after last ESWL.\nThree deaths (2.3% mortality) related to gallstone-relapse\noccurred (1 gallbladder carcinoma, 1 cholangio carcinoma,\n1 acute purulent cholecystitis).\nConclusions: Long-term results of ESWL are unsatisfactory. On the basis of our results, ESWL cannot be\nrecommended for the treatment of symptomatic cholecystolithiasis, especially in young patients. Indication\nfor ESWL in older patients (>70 years) has to be well\nbalanced with the risk of developing gallbladder cancer or other stone related complications. This study serves as a\ncritical reminder of unforeseeable long-term issues that\nmay arise with a newly introduced technique","Source":"Google Scholar","category":"HUMAN","training_data":"Extracorporeal Shockwave Lithotripsy (Eswl) For The Treatment Of Gallbladder Stones: Long-Term Results After More Than 20 Years Aims: We aimed to evaluate the long-term results of\nextracorporeal shockwave lithotripsy (ESWL) as a conservative treatment for symptomatic gallbladder stones.\nThis therapy was used as a non-invasive alternative to\nsurgery in many European countries in the 1980’s and\n1990’s, but experience after some years showed poor\nstone-free rates with frequent relapse of symptoms.\nIntroduction of minimal-invasive, laparoscopic cholecystectomy has replaced this treatment worldwide. This is the\nfirst study examining the results more than 20 years after\nESWL.\nMethods: Retrospective study on all patients treated with\nESWL for uncomplicated, symptomatic gallbladder stones\nat our institution between 1989 and 1990. The endpoints\nwere stone-free recurrence rates, symptomatic or complicated gallbladder disease and subsequent need for surgical\nintervention as well as disease-related mortality.\nResults: From March 1989 to November 1990 some 160\npatients were treated with a total of 217 ESWL sessions.\nAfter exclusion of 34 patients (loss of follow-up), the\ncohort comprised of 126 patients with a mean follow-up of\n23.4 years.\nOnly 22 (18%) patients remained free of symptoms and\ngallstones after the initial treatment during the study period.\nSymptoms recurred at a mean of 3.8 years, in 13 (10%)\nfurther interventional treatment (ESWL, ERCP, etc.) was\nnecessary. Subsequent cholecystectomy was performed in\n91 (72%) patients at a mean of 5.1 years after last ESWL.\nThree deaths (2.3% mortality) related to gallstone-relapse\noccurred (1 gallbladder carcinoma, 1 cholangio carcinoma,\n1 acute purulent cholecystitis).\nConclusions: Long-term results of ESWL are unsatisfactory. On the basis of our results, ESWL cannot be\nrecommended for the treatment of symptomatic cholecystolithiasis, especially in young patients. Indication\nfor ESWL in older patients (>70 years) has to be well\nbalanced with the risk of developing gallbladder cancer or other stone related complications. This study serves as a\ncritical reminder of unforeseeable long-term issues that\nmay arise with a newly introduced technique Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinical features sarcomatoid change patients intrahepatic cholangiocarcinoma prognosis surgical liver resection propensity score matching analysis background intrahepatic cholangiocarcinoma sarcomatoid change icca sc rare histological subtype icca clinical features outcomes surgical resection prognosis still unknown methods retrospectively reviewed clinical data patients histologically proven icca underwent curative liver resection hospital january 2008 december 2018 propensity score matching analysis used match patients without sarcomatoid change ratio 1 4 nomogram integrating significant independent factors overall survival os recurrence free survival rfs constructed predict prognosis icca predictive accuracy ability nomogram determined harrell index c index results total 40 icca sc 160 ordinary icca patients included study rfs os icca sc group significantly lower ordinary icca group p 001 p 002 respectively calibration curve probability survival showed good agreement nomogram prediction actual observation conclusion histological sarcomatoid subtype independent predictor tumor recurrence shorter os icca patients nomogram established provide accurate prognostic prediction icca patients pubmed","probabilities":0.9799733,"Title":"Clinical features of sarcomatoid change in patients with intrahepatic cholangiocarcinoma and prognosis after surgical liver resection: A Propensity Score Matching analysis","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma with sarcomatoid change (iCCA-SC) is a rare histological subtype of iCCA, the clinical features and outcomes after surgical resection on the prognosis is still unknown. METHODS: We retrospectively reviewed the clinical data of patients with histologically proven iCCA who underwent curative liver resection at our hospital between January 2008 and December 2018. Propensity score matching analysis was used to match patients with and without sarcomatoid change at a ratio of 1:4. The nomogram integrating all significant independent factors for overall survival (OS) and recurrence-free survival (RFS) was constructed to predict prognosis for iCCA. The predictive accuracy ability of the nomogram was determined by Harrell's index (C-index). RESULTS: A total of 40 iCCA-SC and 160 ordinary iCCA patients were included in this study. RFS and OS in the iCCA-SC group were significantly lower than those in the ordinary iCCA group (P<.001 and P = .002, respectively). The calibration curve for the probability of survival showed good agreement between the nomogram prediction and actual observation. CONCLUSION: The histological sarcomatoid subtype is an independent predictor of tumor recurrence and shorter OS in iCCA patients. The nomogram we established could provide more accurate prognostic prediction for iCCA patients.","Source":"PubMed","category":"HUMAN","training_data":"Clinical features of sarcomatoid change in patients with intrahepatic cholangiocarcinoma and prognosis after surgical liver resection: A Propensity Score Matching analysis BACKGROUND: Intrahepatic cholangiocarcinoma with sarcomatoid change (iCCA-SC) is a rare histological subtype of iCCA, the clinical features and outcomes after surgical resection on the prognosis is still unknown. METHODS: We retrospectively reviewed the clinical data of patients with histologically proven iCCA who underwent curative liver resection at our hospital between January 2008 and December 2018. Propensity score matching analysis was used to match patients with and without sarcomatoid change at a ratio of 1:4. The nomogram integrating all significant independent factors for overall survival (OS) and recurrence-free survival (RFS) was constructed to predict prognosis for iCCA. The predictive accuracy ability of the nomogram was determined by Harrell's index (C-index). RESULTS: A total of 40 iCCA-SC and 160 ordinary iCCA patients were included in this study. RFS and OS in the iCCA-SC group were significantly lower than those in the ordinary iCCA group (P<.001 and P = .002, respectively). The calibration curve for the probability of survival showed good agreement between the nomogram prediction and actual observation. CONCLUSION: The histological sarcomatoid subtype is an independent predictor of tumor recurrence and shorter OS in iCCA patients. The nomogram we established could provide more accurate prognostic prediction for iCCA patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression prognostic significance livin caspase 3 ki 67 progression human ampullary carcinoma livin new member inhibitor apoptosis proteins family proteins interacts downstream caspases caspase 3 caspase 7 caspase 9 however role human ampullary carcinoma clearly defined immunohistochemistry used evaluate tissue samples patients ampullary carcinomas n 71 using antibodies livin ki 67 proliferation marker caspase 3 livin detected 33 71 cases cytoplasm nucleus 2 cases high livin expression correlated cell differentiation tumor node metastasis stage lymph node metastasis p 0 001 p 0 001 p 0 028 respectively caspase 3 ki 67 expression significantly associated differentiation p 0 001 p 0 008 respectively significant negative correlation livin caspase 3 r 0 575 p 0 001 positive correlation livin ki 67 r 0 308 p 0 009 survival patients high livin expression shorter compared patients low livin expression p 0 001 expression caspase 3 associated overall survival cohort p 0 335 livin expression independent prognostic factor hazard ratio 2 693 p 0 017 lymph node metastasis hazard ratio 4 959 p 0 001 study livin expression significantly correlated proliferation marker ki 67 negatively correlated caspase 3 expression data suggest livin may valuable prognostic factor human ampullary carcinoma pubmed","probabilities":0.962963,"Title":"Expression and prognostic significance of livin, caspase-3, and ki-67 in the progression of human ampullary carcinoma","Abstract":"Livin is a new member of the inhibitor of apoptosis proteins family of proteins that interacts with downstream caspases, such as caspase-3, caspase-7, and caspase-9, however, its role in human ampullary carcinoma has not been clearly defined. Immunohistochemistry was used to evaluate tissue samples from patients with ampullary carcinomas (n=71) using antibodies against livin, Ki-67 (a proliferation marker), and caspase-3. Livin was detected in 33/71 cases (in the cytoplasm of all and in the nucleus of only 2 cases). High livin expression correlated with cell differentiation, tumor-node-metastasis stage, and lymph node metastasis (P=0.001, P<0.001, and P=0.028, respectively). Caspase-3 and Ki-67 expression were significantly associated with differentiation (P<0.001, P=0.008, respectively). There was a significant negative correlation between livin and caspase-3 (r=-0.575, P<0.001), and a positive correlation between livin and Ki-67 (r=0.308, P=0.009). Survival of patients with high livin expression was shorter compared with that of patients with low livin expression (P=0.001). Expression of caspase-3 was not associated with overall survival in this cohort (P=0.335). Livin expression was an independent prognostic factor (hazard ratio 2.693, P=0.017), as was lymph node metastasis (hazard ratio 4.959; P<0.001). In this study livin expression significantly correlated with the proliferation marker Ki-67, but was negatively correlated with caspase-3 expression. These data suggest that livin may be a valuable prognostic factor for human ampullary carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Expression and prognostic significance of livin, caspase-3, and ki-67 in the progression of human ampullary carcinoma Livin is a new member of the inhibitor of apoptosis proteins family of proteins that interacts with downstream caspases, such as caspase-3, caspase-7, and caspase-9, however, its role in human ampullary carcinoma has not been clearly defined. Immunohistochemistry was used to evaluate tissue samples from patients with ampullary carcinomas (n=71) using antibodies against livin, Ki-67 (a proliferation marker), and caspase-3. Livin was detected in 33/71 cases (in the cytoplasm of all and in the nucleus of only 2 cases). High livin expression correlated with cell differentiation, tumor-node-metastasis stage, and lymph node metastasis (P=0.001, P<0.001, and P=0.028, respectively). Caspase-3 and Ki-67 expression were significantly associated with differentiation (P<0.001, P=0.008, respectively). There was a significant negative correlation between livin and caspase-3 (r=-0.575, P<0.001), and a positive correlation between livin and Ki-67 (r=0.308, P=0.009). Survival of patients with high livin expression was shorter compared with that of patients with low livin expression (P=0.001). Expression of caspase-3 was not associated with overall survival in this cohort (P=0.335). Livin expression was an independent prognostic factor (hazard ratio 2.693, P=0.017), as was lymph node metastasis (hazard ratio 4.959; P<0.001). In this study livin expression significantly correlated with the proliferation marker Ki-67, but was negatively correlated with caspase-3 expression. These data suggest that livin may be a valuable prognostic factor for human ampullary carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"transarterial chemoembolization favorable postoperative management improve prognosis hepatitis b virus associated intrahepatic cholangiocarcinoma surgical resection background information regarding transarterial chemoembolization tace postoperative management hepatic resection patients hepatitis b virus hbv associated intrahepatic cholangiocarcinoma icc methods forty two patients pathological confirmation hbv associated icc enrolled prognostic impact clinicopathological factors well postoperative tace evaluated computed tomography findings hbv associated icc assessed results tumor size larger 5 cm hazard ratio hr 5 654 95 confidence interval ci 1 175 27 204 p 0 031 postoperative tace hr 0 123 95 ci 0 023 0 643 p 0 013 lymph node metastasis hr 3 284 95 ci 1 236 8 724 p 0 017 revealed independently associated survival outcomes patients hbv associated icc application tace postoperative management control early local recurrence basis hepatic arterial phase enhancement significantly prolonged survival outcomes 1 yr 88 9 3 yr 77 8 5 yr 66 7 compared patients receive tace 1 yr 63 6 3 yr 30 8 5 yr 13 0 analyzed according status hepatic arterial phase arterial phase enhancement demonstrated favorable trend prognosis patients hbv associated icc without statistical significance hr 0 435 95 ci 0 140 1 359 p 0 141 tace independently improved overall survival patients arterial phase enhancement hr 0 105 95 ci 0 014 0 774 p 0 027 conclusions put together results indicate postoperative tace effectively improves prognosis hbv associated icc arterial phase enhancement ct scans large sized trials required results applied clinical medicine pubmed","probabilities":0.9799733,"Title":"Transarterial Chemoembolization: A Favorable Postoperative Management to Improve Prognosis of Hepatitis B Virus-associated Intrahepatic Cholangiocarcinoma after Surgical Resection","Abstract":"Background: There is no information regarding transarterial chemoembolization (TACE) as a postoperative management after hepatic resection for patients with hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC). Methods: Forty-two patients with pathological confirmation of HBV-associated ICC were enrolled. Prognostic impact of the clinicopathological factors as well as postoperative TACE were evaluated. Computed tomography findings of HBV-associated ICC were assessed. Results: Tumor size of larger than 5 cm (hazard ratio [HR], 5.654; 95% confidence interval [CI], 1.175 to 27.204; P = 0.031), postoperative TACE (HR, 0.123; 95% CI, 0.023 to 0.643; P = 0.013), and lymph node metastasis (HR, 3.284; 95% CI, 1.236 to 8.724; P = 0.017) revealed to be independently associated with survival outcomes of patients with HBV-associated ICC. Application of TACE, as a postoperative management to control early local recurrence on the basis of hepatic arterial phase enhancement, significantly prolonged survival outcomes (1-yr, 88.9%; 3-yr, 77.8%; 5-yr, 66.7%), compared to the patients who did not receive TACE (1-yr, 63.6%; 3-yr, 30.8%; 5-yr, 13.0%). When analyzed according to the status of hepatic arterial phase, arterial phase enhancement demonstrated a favorable trend on prognosis of patients with HBV-associated ICC without statistical significance (HR, 0.435; 95% CI, 0.140 to 1.359; P = 0.141), and TACE independently improved overall survival of patients with arterial phase enhancement (HR, 0.105; 95% CI, 0.014 to 0.774; P = 0.027). Conclusions: Put together, our results indicate that postoperative TACE effectively improves prognosis of HBV-associated ICC with arterial phase enhancement in CT scans. Large-sized trials are required for our results to be applied in clinical medicine.","Source":"PubMed","category":"HUMAN","training_data":"Transarterial Chemoembolization: A Favorable Postoperative Management to Improve Prognosis of Hepatitis B Virus-associated Intrahepatic Cholangiocarcinoma after Surgical Resection Background: There is no information regarding transarterial chemoembolization (TACE) as a postoperative management after hepatic resection for patients with hepatitis B virus (HBV)-associated intrahepatic cholangiocarcinoma (ICC). Methods: Forty-two patients with pathological confirmation of HBV-associated ICC were enrolled. Prognostic impact of the clinicopathological factors as well as postoperative TACE were evaluated. Computed tomography findings of HBV-associated ICC were assessed. Results: Tumor size of larger than 5 cm (hazard ratio [HR], 5.654; 95% confidence interval [CI], 1.175 to 27.204; P = 0.031), postoperative TACE (HR, 0.123; 95% CI, 0.023 to 0.643; P = 0.013), and lymph node metastasis (HR, 3.284; 95% CI, 1.236 to 8.724; P = 0.017) revealed to be independently associated with survival outcomes of patients with HBV-associated ICC. Application of TACE, as a postoperative management to control early local recurrence on the basis of hepatic arterial phase enhancement, significantly prolonged survival outcomes (1-yr, 88.9%; 3-yr, 77.8%; 5-yr, 66.7%), compared to the patients who did not receive TACE (1-yr, 63.6%; 3-yr, 30.8%; 5-yr, 13.0%). When analyzed according to the status of hepatic arterial phase, arterial phase enhancement demonstrated a favorable trend on prognosis of patients with HBV-associated ICC without statistical significance (HR, 0.435; 95% CI, 0.140 to 1.359; P = 0.141), and TACE independently improved overall survival of patients with arterial phase enhancement (HR, 0.105; 95% CI, 0.014 to 0.774; P = 0.027). Conclusions: Put together, our results indicate that postoperative TACE effectively improves prognosis of HBV-associated ICC with arterial phase enhancement in CT scans. Large-sized trials are required for our results to be applied in clinical medicine. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cxcl7 promotes proliferation invasion cholangiocarcinoma cells cxcl7 important chemoattractant cytokine signals binding receptor cxcr2 recent studies demonstrated cxcl7 cxcr2 signaling plays promoting role several common malignancies including lung renal colon breast cancer however regulatory role cxcl7 cholangiocarcinoma well underlying mechanism previously reported herein found positive expression cxcl7 cholangiocarcinoma tissues compared adjacent non tumor tissues high cxcl7 expression significantly correlated poor differentiation lymph node metastasis vascular invasion advanced clinical stage associated age gender tumor size besides expression cxcl7 significantly associated ki67 expression associated ca199 afp p53 expression cholangiocarcinoma moreover overall survival cholangiocarcinoma patients high cxcl7 expression significantly shorter low cxcl7 expression vitro study indicated cxcl7 cxcr2 also positively expressed several common cholangiocarcinoma cell lines including hucct1 huh28 qbc939 egi 1 oz witt sirna induced inhibition cxcl7 significantly reduced proliferation invasion qbc939 cells contrary overexpression cxcl7 markedly promoted malignant phenotypes qbc939 cells note conditioned medium cxcl7 overexpresing human hepatic stellate cells also promote proliferation invasion qbc939 cells suggesting cxcl7 may also play oncogenic role cholangiocarcinoma paracrine dependent manner autocrine dependent manner molecular assay data suggested akt signaling pathway involved cxcl7 mediated malignant phenotypes qbc939 cells summary study suggests cxcl7 plays promoting role regulating growth metastasis cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Cxcl7 Promotes Proliferation And Invasion Of Cholangiocarcinoma Cells","Abstract":"CXCL7 is an important chemoattractant cytokine, which signals through binding to its receptor CXCR2. Recent studies have demonstrated that the CXCL7/CXCR2 signaling plays a promoting role in several common malignancies, including lung, renal, colon, and breast cancer. However, the regulatory role of CXCL7, in cholangiocarcinoma, as well as the underlying mechanism, has not been previously reported. Herein, we found more positive expression of CXCL7 in cholangiocarcinoma tissues compared to adjacent non-tumor tissues. High CXCL7 expression was significantly correlated with poor differentiation, lymph node metastasis, vascular invasion and advanced clinical stage, but was not associated with age, gender, or tumor size. Besides, the expression of CXCL7 was significantly associated with the Ki67 expression, but not associated with CA199, AFP, or P53 expression in cholangiocarcinoma. Moreover, the overall survival of cholangiocarcinoma patients with high CXCL7 expression was significantly shorter than those with low CXCL7 expression. In vitro study indicated that CXCL7 and CXCR2 were also positively expressed in several common cholangiocarcinoma cell lines, including HuCCT1, HuH28, QBC939, EGI-1, OZ and WITT. SiRNA-induced inhibition of CXCL7 significantly reduced the proliferation and invasion of QBC939 cells. On the contrary, overexpression of CXCL7 markedly promoted these malignant phenotypes of QBC939 cells. Of note, the conditioned medium of CXCL7-overexpresing human hepatic stellate cells could also promote the proliferation and invasion of QBC939 cells, suggesting that CXCL7 may also play an oncogenic role in cholangiocarcinoma in a paracrine-dependent manner, not only in an autocrine-dependent manner. Molecular assay data suggested that the AKT signaling pathway was involved in the CXCL7-mediated malignant phenotypes of QBC939 cells. In summary, our study suggests that CXCL7 plays a promoting role in regulating the growth and metastasis of cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Cxcl7 Promotes Proliferation And Invasion Of Cholangiocarcinoma Cells CXCL7 is an important chemoattractant cytokine, which signals through binding to its receptor CXCR2. Recent studies have demonstrated that the CXCL7/CXCR2 signaling plays a promoting role in several common malignancies, including lung, renal, colon, and breast cancer. However, the regulatory role of CXCL7, in cholangiocarcinoma, as well as the underlying mechanism, has not been previously reported. Herein, we found more positive expression of CXCL7 in cholangiocarcinoma tissues compared to adjacent non-tumor tissues. High CXCL7 expression was significantly correlated with poor differentiation, lymph node metastasis, vascular invasion and advanced clinical stage, but was not associated with age, gender, or tumor size. Besides, the expression of CXCL7 was significantly associated with the Ki67 expression, but not associated with CA199, AFP, or P53 expression in cholangiocarcinoma. Moreover, the overall survival of cholangiocarcinoma patients with high CXCL7 expression was significantly shorter than those with low CXCL7 expression. In vitro study indicated that CXCL7 and CXCR2 were also positively expressed in several common cholangiocarcinoma cell lines, including HuCCT1, HuH28, QBC939, EGI-1, OZ and WITT. SiRNA-induced inhibition of CXCL7 significantly reduced the proliferation and invasion of QBC939 cells. On the contrary, overexpression of CXCL7 markedly promoted these malignant phenotypes of QBC939 cells. Of note, the conditioned medium of CXCL7-overexpresing human hepatic stellate cells could also promote the proliferation and invasion of QBC939 cells, suggesting that CXCL7 may also play an oncogenic role in cholangiocarcinoma in a paracrine-dependent manner, not only in an autocrine-dependent manner. Molecular assay data suggested that the AKT signaling pathway was involved in the CXCL7-mediated malignant phenotypes of QBC939 cells. In summary, our study suggests that CXCL7 plays a promoting role in regulating the growth and metastasis of cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"clinical outcome immunotherapy dendritic cell vaccine cytokine induced killer cell therapy hepatobiliary pancreatic cancer aim study determine therapeutic effects adoptive immunotherapy following dendritic cell dc vaccine cytokine induced killer cik cell therapy evaluate cytotoxicity survival benefits quality life qol changes patients hepatobiliary pancreatic cancer hpc performed retrospective analysis 407 clinical cases including 77 patients hpc received immunotherapy dc vaccine cik cells group 330 patients similar characteristics underwent baseline treatment receive immunotherapy non immunotherapy ni group control group follow period 294 207 5 days median survival time mst two groups compared using kaplan meier method group 61 patients developed positive delayed type hypersensitivity response 65 patients exhibited improvement qol notable adverse events included fever 28 insomnia 25 anorexia 17 skin rash 12 arthralgia 31 severe toxicities observed patients group addition mst significantly longer group compared ni group p 0 014 thus dc vaccine cik cell therapy associated mild adverse effects able induce immune response effectively eliminate tumor cells thereby improving qol prolonging mst patients stn","probabilities":1.0,"Title":"Clinical Outcome Of Immunotherapy With Dendritic Cell Vaccine And Cytokine-Induced Killer Cell Therapy In Hepatobiliary And Pancreatic Cancer","Abstract":"The aim of this study was to determine the therapeutic effects of adoptive immunotherapy following dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell therapy and evaluate its cytotoxicity, survival benefits and quality of life (QOL) changes in patients with hepatobiliary and pancreatic cancer (HPC). We performed a retrospective analysis of 407 clinical cases, including 77 patients with HPC who received immunotherapy with DC vaccine and CIK cells (I group) and 330 patients with similar characteristics who underwent baseline treatment but did not receive immunotherapy [non-immunotherapy (NI) group)] as the control group. After a follow-up period of 294±207.5 days, the median survival time (MST) of the two groups was compared using the Kaplan-Meier method. In the I group, 61% of the patients developed a positive, delayed-type hypersensitivity response and 65% of the patients exhibited an improvement in QOL. The most notable adverse events included fever (28%), insomnia (25%), anorexia (17%), skin rash (12%) and arthralgia (31%). No severe toxicities were observed in patients in the I group; in addition, the MST was significantly longer in the I group compared with that in the NI group (P=0.014). Thus, the DC vaccine and CIK cell therapy was associated with mild adverse effects, but was able to induce an immune response and effectively eliminate tumor cells, thereby improving the QOL and prolonging the MST of the patients.","Source":"STN","category":"HUMAN","training_data":"Clinical Outcome Of Immunotherapy With Dendritic Cell Vaccine And Cytokine-Induced Killer Cell Therapy In Hepatobiliary And Pancreatic Cancer The aim of this study was to determine the therapeutic effects of adoptive immunotherapy following dendritic cell (DC) vaccine and cytokine-induced killer (CIK) cell therapy and evaluate its cytotoxicity, survival benefits and quality of life (QOL) changes in patients with hepatobiliary and pancreatic cancer (HPC). We performed a retrospective analysis of 407 clinical cases, including 77 patients with HPC who received immunotherapy with DC vaccine and CIK cells (I group) and 330 patients with similar characteristics who underwent baseline treatment but did not receive immunotherapy [non-immunotherapy (NI) group)] as the control group. After a follow-up period of 294±207.5 days, the median survival time (MST) of the two groups was compared using the Kaplan-Meier method. In the I group, 61% of the patients developed a positive, delayed-type hypersensitivity response and 65% of the patients exhibited an improvement in QOL. The most notable adverse events included fever (28%), insomnia (25%), anorexia (17%), skin rash (12%) and arthralgia (31%). No severe toxicities were observed in patients in the I group; in addition, the MST was significantly longer in the I group compared with that in the NI group (P=0.014). Thus, the DC vaccine and CIK cell therapy was associated with mild adverse effects, but was able to induce an immune response and effectively eliminate tumor cells, thereby improving the QOL and prolonging the MST of the patients. STN","prediction_labels":"HUMAN"},{"cleaned":"ampullectomy versus pancreaticoduodenectomy ampullary tumors background considerable controversy surrounds treatment ampullary neoplasms report describes authors experiences regarding choice either ampullectomy pancreaticoduodenectomy treatment ampullary tumors methods demographics statistical findings concerning diagnosis surgical risks including morbidity mortality outcomes evaluated compared ampullectomy pancreaticoduodenectomy groups ampullary tumors retrieved prospectively collected computer database 992 periampullary tumors resected period 1965 2013 results total 377 patients ampullary tumors included 15 underwent ampullectomy 362 underwent pancreaticoduodenectomy overall false negative rate diagnosis ampullary malignancy 11 2 specificity 50 0 positive predictive value 98 3 negative predictive value 12 2 overall accuracy 87 6 77 5 preoperative endoscopic biopsy 83 9 intraoperative frozen section biopsy ampullectomy associated shorter postoperative stays lower surgical morbidity statistical difference observed two groups regarding surgical mortality pancreatic leakage gastric atonia tumor recurrence rate lower pancreaticoduodenectomy difference groups significant overall difference survival observed two groups conclusion biopsy routinely reliable pancreaticoduodenectomy preferable ampullectomy ampullary tumor uncertain diagnosis ampullectomy associated lower surgical morbidity therefore remain armamentarium pancreatic surgeon comorbidity precludes major surgery google scholar","probabilities":0.9799733,"Title":"Ampullectomy Versus Pancreaticoduodenectomy For Ampullary Tumors","Abstract":"Background\nConsiderable controversy surrounds the treatment of ampullary neoplasms. This report describes the authors' experiences regarding the choice of either ampullectomy or pancreaticoduodenectomy for treatment of ampullary tumors.\nMethods\nDemographics, statistical findings concerning diagnosis, surgical risks including morbidity and mortality, and outcomes were evaluated and compared between the ampullectomy and pancreaticoduodenectomy groups for ampullary tumors retrieved from a prospectively collected computer database of 992 periampullary tumors resected during the period from 1965 to 2013.\nResults\nA total of 377 patients with ampullary tumors were included; 15 underwent ampullectomy and 362 underwent pancreaticoduodenectomy. The overall false-negative rate for diagnosis of ampullary malignancy was 11.2%, specificity was 50.0%, positive predictive value was 98.3%, negative predictive value was 12.2%, and the overall accuracy was 87.6% (77.5% by preoperative endoscopic biopsy and 83.9% by intraoperative frozen-section biopsy). Ampullectomy was associated with shorter postoperative stays and lower surgical morbidity. There was no statistical difference observed between the two groups regarding surgical mortality, pancreatic leakage, or gastric atonia. The tumor recurrence rate was lower after pancreaticoduodenectomy, but the difference between the groups was not significant. Overall, there was no difference in survival observed between the two groups.\nConclusion\nBecause biopsy is not routinely reliable, pancreaticoduodenectomy is preferable to ampullectomy for an ampullary tumor of uncertain diagnosis. Ampullectomy is associated with lower surgical morbidity and should therefore remain in the armamentarium of the pancreatic surgeon when comorbidity precludes major surgery.","Source":"Google Scholar","category":"HUMAN","training_data":"Ampullectomy Versus Pancreaticoduodenectomy For Ampullary Tumors Background\nConsiderable controversy surrounds the treatment of ampullary neoplasms. This report describes the authors' experiences regarding the choice of either ampullectomy or pancreaticoduodenectomy for treatment of ampullary tumors.\nMethods\nDemographics, statistical findings concerning diagnosis, surgical risks including morbidity and mortality, and outcomes were evaluated and compared between the ampullectomy and pancreaticoduodenectomy groups for ampullary tumors retrieved from a prospectively collected computer database of 992 periampullary tumors resected during the period from 1965 to 2013.\nResults\nA total of 377 patients with ampullary tumors were included; 15 underwent ampullectomy and 362 underwent pancreaticoduodenectomy. The overall false-negative rate for diagnosis of ampullary malignancy was 11.2%, specificity was 50.0%, positive predictive value was 98.3%, negative predictive value was 12.2%, and the overall accuracy was 87.6% (77.5% by preoperative endoscopic biopsy and 83.9% by intraoperative frozen-section biopsy). Ampullectomy was associated with shorter postoperative stays and lower surgical morbidity. There was no statistical difference observed between the two groups regarding surgical mortality, pancreatic leakage, or gastric atonia. The tumor recurrence rate was lower after pancreaticoduodenectomy, but the difference between the groups was not significant. Overall, there was no difference in survival observed between the two groups.\nConclusion\nBecause biopsy is not routinely reliable, pancreaticoduodenectomy is preferable to ampullectomy for an ampullary tumor of uncertain diagnosis. Ampullectomy is associated with lower surgical morbidity and should therefore remain in the armamentarium of the pancreatic surgeon when comorbidity precludes major surgery.\n Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"decreased expression hsa mir 372 predicts poor prognosis patients gallbladder cancer affecting chloride intracellular channel 1 reported hsa microrna mirna mir 372 functions tumor suppressor oncogene various digestive system tumors however roles gallbladder cancer gbc yet established present study aimed determine expression clinical relevance hsa mir 372 gbc expression hsa mir 372 80 pairs human gbc tissues adjacent normal gallbladder tissues measured reverse transcription quantitative polymerase chain reaction subsequently associations hsa mir 372 expression levels clinicopathological characteristics patients gbc determined using 2 test furthermore kaplan meier method cox regression analysis performed evaluate association hsa mir 372 expression prognosis patients gbc furthermore dual luciferase reporter assay western blot analysis performed predict verify target gene hsa mir 372 results demonstrated markedly lower hsa mir 372 expression observed gbc tissues associated poor prognosis patients gbc downregulated expression hsa mir 372 negatively associated tumor histological grade tumor node metastasis stage lymph node metastasis distant metastasis however association observed reduced hsa mir 372 expression patient gender age tumor size gallbladder stones multivariate cox regression analysis revealed hsa mir 372 expression histological grade lymph node metastasis independent prognostic factors overall survival patients gbc chloride intracellular channel 1 clic1 previously reported effective biomarker predicting prognosis gbc notably results present study indicated clic1 may direct target gene hsa mir 372 conclusion current study provides first statistically convincing evidence downregulation hsa mir 372 may occur gbc tissues may associated aggressive progressive tumor behavior affecting clic1 expression stn","probabilities":1.0,"Title":"Decreased Expression Of Hsa-Mir-372 Predicts Poor Prognosis In Patients With Gallbladder Cancer By Affecting Chloride Intracellular Channel 1","Abstract":"It has been reported that hsa‑microRNA (miRNA/miR)‑372 functions as a tumor suppressor or oncogene in various digestive system tumors, however, its roles in gallbladder cancer (GBC) are yet to be established. The present study aimed to determine the expression and clinical relevance of hsa‑miR‑372 in GBC. The expression of hsa‑miR‑372 in 80 pairs of human GBC tissues and adjacent normal gallbladder tissues was measured by reverse transcription‑quantitative polymerase chain reaction. Subsequently, the associations between hsa‑miR‑372 expression levels and the clinicopathological characteristics of patients with GBC were determined using χ2 test. Furthermore, Kaplan‑Meier method and Cox regression analysis were performed to evaluate the association between hsa‑miR‑372 expression and the prognosis of patients with GBC. Furthermore, a dual‑luciferase reporter assay and western blot analysis were performed to predict and verify the target gene of hsa‑miR‑372. The results demonstrated that markedly lower hsa‑miR‑372 expression was observed in GBC tissues, which was associated with poor prognosis in patients with GBC. Downregulated expression of hsa‑miR‑372 was negatively associated with tumor histological grade, tumor‑node‑metastasis stage, lymph node metastasis and distant metastasis, however, no association was observed between reduced hsa‑miR‑372 expression and patient gender, age, tumor size and gallbladder stones. Multivariate Cox regression analysis revealed that hsa‑miR‑372 expression, histological grade and lymph node metastasis were independent prognostic factors for overall survival in patients with GBC. Chloride intracellular channel 1 (CLIC1) was previously reported to be an effective biomarker for predicting the prognosis of GBC. Notably, the results of the present study indicated that CLIC1 may be a direct target gene of hsa‑miR‑372. In conclusion, the current study provides the first statistically convincing evidence that downregulation of hsa‑miR‑372 may occur in GBC tissues, which may be associated with aggressive and progressive tumor behavior by affecting CLIC1 expression.","Source":"STN","category":"ANIMAL","training_data":"Decreased Expression Of Hsa-Mir-372 Predicts Poor Prognosis In Patients With Gallbladder Cancer By Affecting Chloride Intracellular Channel 1 It has been reported that hsa‑microRNA (miRNA/miR)‑372 functions as a tumor suppressor or oncogene in various digestive system tumors, however, its roles in gallbladder cancer (GBC) are yet to be established. The present study aimed to determine the expression and clinical relevance of hsa‑miR‑372 in GBC. The expression of hsa‑miR‑372 in 80 pairs of human GBC tissues and adjacent normal gallbladder tissues was measured by reverse transcription‑quantitative polymerase chain reaction. Subsequently, the associations between hsa‑miR‑372 expression levels and the clinicopathological characteristics of patients with GBC were determined using χ2 test. Furthermore, Kaplan‑Meier method and Cox regression analysis were performed to evaluate the association between hsa‑miR‑372 expression and the prognosis of patients with GBC. Furthermore, a dual‑luciferase reporter assay and western blot analysis were performed to predict and verify the target gene of hsa‑miR‑372. The results demonstrated that markedly lower hsa‑miR‑372 expression was observed in GBC tissues, which was associated with poor prognosis in patients with GBC. Downregulated expression of hsa‑miR‑372 was negatively associated with tumor histological grade, tumor‑node‑metastasis stage, lymph node metastasis and distant metastasis, however, no association was observed between reduced hsa‑miR‑372 expression and patient gender, age, tumor size and gallbladder stones. Multivariate Cox regression analysis revealed that hsa‑miR‑372 expression, histological grade and lymph node metastasis were independent prognostic factors for overall survival in patients with GBC. Chloride intracellular channel 1 (CLIC1) was previously reported to be an effective biomarker for predicting the prognosis of GBC. Notably, the results of the present study indicated that CLIC1 may be a direct target gene of hsa‑miR‑372. In conclusion, the current study provides the first statistically convincing evidence that downregulation of hsa‑miR‑372 may occur in GBC tissues, which may be associated with aggressive and progressive tumor behavior by affecting CLIC1 expression. STN","prediction_labels":"ANIMAL"},{"cleaned":"long non coding rna epic1 promotes cholangiocarcinoma cell growth cholangiocarcinoma cca frequently observed biliary tract malignancy low survival rate addition constrained treatment options however fundamental molecular mechanism underlying malignant progression cca quite ambiguous recent studies reported long non coding rna lncrna might play critical roles regulating chemo resistant multiple types cancer study results indicate lncrna epic1 expression significantly increased cholangiocarcinoma tissues compared adjacent normal tissues also expression also increased several cca cancer cell lines human normal immortalized cholangiocyte cell loss gain lnc epic1 contributes cca cell growth colony formation cell apoptosis also cell cycle myc reported directly interact lnc epic1 several cancer cells myc targets including cyclin d cdk9 downregulated lnc epic1 sirna myc knockout also suppresses cca cell growth colony formation cell apoptosis however lnc epic1 knockdown failed enhance myc ko induced suppression cca tumor progression rna immunoprecipitation rip results showed direct interaction lnc epic1 myc taken together results show lnc epic1 promotes cca cancer progression targeting myc stn","probabilities":0.9467213,"Title":"Long Non-Coding Rna Epic1 Promotes Cholangiocarcinoma Cell Growth","Abstract":"Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options. However, the fundamental molecular mechanism underlying malignant progression of CCA is quite ambiguous. Recent studies reported that long non-coding RNA (lncRNA) might play critical roles in regulating chemo-resistant of multiple types of cancer. In this study, our results indicate that the LncRNA-EPIC1 expression were significantly increased in cholangiocarcinoma tissues, compared to adjacent normal tissues. And also, its expression also increased in several CCA cancer cell lines than that in human normal immortalized cholangiocyte cell. Loss-and-gain of Lnc-EPIC1 contributes to the CCA cell growth, colony formation, cell apoptosis and also cell cycle. Myc has been reported to directly interact with Lnc-EPIC1 in several cancer cells. Myc targets, including Cyclin A/D and CDK9 were downregulated by Lnc-EPIC1 siRNA. Myc knockout also suppresses the CCA cell growth, colony formation and cell apoptosis. However, Lnc-EPIC1 knockdown failed to enhance the Myc-KO-induced suppression of CCA tumor progression. RNA immunoprecipitation (RIP) results showed the direct interaction between Lnc-EPIC1 and Myc. Taken together, our results show that Lnc-EPIC1 promotes CCA cancer progression by targeting Myc.","Source":"STN","category":"ANIMAL","training_data":"Long Non-Coding Rna Epic1 Promotes Cholangiocarcinoma Cell Growth Cholangiocarcinoma (CCA) is the as the most frequently observed biliary tract malignancy, which has low survival rate in addition to constrained treatment options. However, the fundamental molecular mechanism underlying malignant progression of CCA is quite ambiguous. Recent studies reported that long non-coding RNA (lncRNA) might play critical roles in regulating chemo-resistant of multiple types of cancer. In this study, our results indicate that the LncRNA-EPIC1 expression were significantly increased in cholangiocarcinoma tissues, compared to adjacent normal tissues. And also, its expression also increased in several CCA cancer cell lines than that in human normal immortalized cholangiocyte cell. Loss-and-gain of Lnc-EPIC1 contributes to the CCA cell growth, colony formation, cell apoptosis and also cell cycle. Myc has been reported to directly interact with Lnc-EPIC1 in several cancer cells. Myc targets, including Cyclin A/D and CDK9 were downregulated by Lnc-EPIC1 siRNA. Myc knockout also suppresses the CCA cell growth, colony formation and cell apoptosis. However, Lnc-EPIC1 knockdown failed to enhance the Myc-KO-induced suppression of CCA tumor progression. RNA immunoprecipitation (RIP) results showed the direct interaction between Lnc-EPIC1 and Myc. Taken together, our results show that Lnc-EPIC1 promotes CCA cancer progression by targeting Myc. STN","prediction_labels":"ANIMAL"},{"cleaned":"second line chemotherapy patients advanced recurrent biliary tract cancer single center retrospective analysis 294 cases purpose survival benefit first line chemotherapy ct1 biliary tract cancer btc established role second line chemotherapy ct2 fully elucidated yet methods consecutive advanced btc patients receiving ct1 2000 2016 retrospectively studied investigated safety efficacy ct2 prognostic factors residual survival ct1 explored subgroups benefit ct2 results among 294 patients receiving ct1 advanced btc ct2 given 139 patients 47 ct2 provided response rate 4 disease control rate 52 median progression free survival 2 8 overall survival 7 7 months respectively ct2 associated longer residual survival ct1 hazard ratio hr 0 61 p 0 01 well ps 0 1 hr 0 53 p 0 01 best response ct1 pd hr 1 46 p 0 01 cea 5 0 ng ml hr 1 69 p 0 01 effects ct2 homogeneous across almost subgroups prominent patients age 70 years hr 0 32 p interaction 0 02 ca19 9 200 iu ml hr 0 41 p interaction 0 08 cea 5 0 ng ml hr 0 41 p interaction 0 06 conclusions introduction rate ct2 47 although efficacy ct2 modest terms tumor response associated better survival investigations necessary develop effective regimens select patients benefit ct2 stn","probabilities":0.9799733,"Title":"Second-Line Chemotherapy In Patients With Advanced Or Recurrent Biliary Tract Cancer: A Single Center Retrospective Analysis Of 294 Cases","Abstract":"Purpose The survival benefit of first-line chemotherapy (CT1) for biliary tract cancer (BTC) is now established but the role of second-line chemotherapy (CT2) has not been fully elucidated yet. Methods Consecutive advanced BTC patients receiving CT1 between 2000 and 2016 were retrospectively studied. We investigated the safety and efficacy of CT2, prognostic factors for residual survival after CT1, and explored subgroups who would benefit from CT2. Results Among 294 patients receiving CT1 for advanced BTC, CT2 was given in 139 patients (47%). CT2 provided a response rate of 4%, a disease control rate of 52%, a median progression-free survival of 2.8 and overall survival of 7.7 months, respectively. CT2 was associated with longer residual survival after CT1 (hazard ratio [HR] 0.61, p < 0.01), as well as PS of 0-1 (HR 0.53, p < 0.01), best response to CT1 of PD (HR 1.46, p = 0.01), and CEA ≥5.0 ng/mL (HR 1.69, p < 0.01). The effects of CT2 were homogeneous across almost all subgroups but were more prominent in patients with age ≥ 70 years (HR 0.32, p for interaction =0.02), CA19-9 ≥ 200 IU/mL (HR 0.41, p for interaction = 0.08) and CEA ≥5.0 ng/mL (HR 0.41, p for interaction = 0.06). Conclusions The introduction rate of CT2 was 47%. Although the efficacy of CT2 was modest in terms of tumor response, it was associated with better survival. Further investigations are necessary both to develop more effective regimens and to select patients who will benefit from CT2.","Source":"STN","category":"HUMAN","training_data":"Second-Line Chemotherapy In Patients With Advanced Or Recurrent Biliary Tract Cancer: A Single Center Retrospective Analysis Of 294 Cases Purpose The survival benefit of first-line chemotherapy (CT1) for biliary tract cancer (BTC) is now established but the role of second-line chemotherapy (CT2) has not been fully elucidated yet. Methods Consecutive advanced BTC patients receiving CT1 between 2000 and 2016 were retrospectively studied. We investigated the safety and efficacy of CT2, prognostic factors for residual survival after CT1, and explored subgroups who would benefit from CT2. Results Among 294 patients receiving CT1 for advanced BTC, CT2 was given in 139 patients (47%). CT2 provided a response rate of 4%, a disease control rate of 52%, a median progression-free survival of 2.8 and overall survival of 7.7 months, respectively. CT2 was associated with longer residual survival after CT1 (hazard ratio [HR] 0.61, p < 0.01), as well as PS of 0-1 (HR 0.53, p < 0.01), best response to CT1 of PD (HR 1.46, p = 0.01), and CEA ≥5.0 ng/mL (HR 1.69, p < 0.01). The effects of CT2 were homogeneous across almost all subgroups but were more prominent in patients with age ≥ 70 years (HR 0.32, p for interaction =0.02), CA19-9 ≥ 200 IU/mL (HR 0.41, p for interaction = 0.08) and CEA ≥5.0 ng/mL (HR 0.41, p for interaction = 0.06). Conclusions The introduction rate of CT2 was 47%. Although the efficacy of CT2 was modest in terms of tumor response, it was associated with better survival. Further investigations are necessary both to develop more effective regimens and to select patients who will benefit from CT2. STN","prediction_labels":"HUMAN"},{"cleaned":"her2 amplification rare event non liver fluke associated cholangiocarcinogenesis background cholangiocarcinoma rapidly fatal cancer entity median survival less one year contrast many malignancies substantial therapeutic breakthrough made past decades thereby limiting treatment cytotoxic chemotherapy little beneficial effect patients targeted therapy tailored individual shown substantial success recent past promising avenue cancer therapy methods study determined frequency amplification her2 gene comprehensive well characterized european cholangiocarcinoma cohort encompassing 436 patients including intrahepatic n 155 proximal n 155 distal n 126 cholangiocarcinoma strict application combined immunohistochemical situ hybridization algorithm following current guidelines her2 assessment gastric cancer results identified proportion 1 4 n 6 patients demonstrated her2 gene amplification highest rate among distal cholangiocarcinoma patients 2 4 none patients equivocal 2 immunohistochemical staining results exhibited gene amplification molecularly four five patients her2 positivity gene amplification already present concomitantly tested high grade biliary intraepithelial neoplasia 80 her2 gene amplification significantly associated clinical parameters including survival conclusions study identifies her2 gene amplification rare event cholangiocarcinoma western population occurring already high grade bilin subset patients furthermore provide robust testing algorithm may used prior therapy administration future clinical trials evaluating role her2 predictive marker cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Her2 Amplification Is A Rare Event In Non-Liver-Fluke Associated Cholangiocarcinogenesis","Abstract":"Background: Cholangiocarcinoma is a rapidly fatal cancer entity with a median survival of less than one year. In contrast to many other malignancies, no substantial therapeutic breakthrough has been made in the past few decades, thereby limiting the treatment to cytotoxic chemotherapy with little beneficial effect for most patients. Targeted therapy tailored to the individual has shown substantial success in the recent past as a promising avenue for cancer therapy. \r\n\r\n Methods: In this study, we determined the frequency of amplification of the HER2 gene in a comprehensive and well-characterized European cholangiocarcinoma cohort encompassing 436 patients including intrahepatic (n = 155), proximal (n = 155) and distal (n = 126) cholangiocarcinoma by strict application of a combined immunohistochemical and in situ hybridization algorithm following the current guidelines for HER2 assessment in gastric cancer. \r\n\r\n Results: We identified a proportion of 1.4% (n = 6) patients that demonstrated HER2 gene amplification, with the highest rate among the distal cholangiocarcinoma patients (2.4%). None of the patients with equivocal (2+) immunohistochemical staining results exhibited gene amplification molecularly. In four of the five patients with HER2 positivity, gene amplification was already present in concomitantly tested high-grade biliary intraepithelial neoplasia (80%). HER2 gene amplification was not significantly associated with other clinical parameters, including survival. \r\n\r\n Conclusions: This study identifies HER2 gene amplification as a rare event in cholangiocarcinoma of the Western population, occurring already in high-grade BilIN in a subset of patients. Furthermore, we provide a robust testing algorithm that may be used prior to therapy administration in future clinical trials evaluating the role of HER2 as a predictive marker in cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Her2 Amplification Is A Rare Event In Non-Liver-Fluke Associated Cholangiocarcinogenesis Background: Cholangiocarcinoma is a rapidly fatal cancer entity with a median survival of less than one year. In contrast to many other malignancies, no substantial therapeutic breakthrough has been made in the past few decades, thereby limiting the treatment to cytotoxic chemotherapy with little beneficial effect for most patients. Targeted therapy tailored to the individual has shown substantial success in the recent past as a promising avenue for cancer therapy. \r\n\r\n Methods: In this study, we determined the frequency of amplification of the HER2 gene in a comprehensive and well-characterized European cholangiocarcinoma cohort encompassing 436 patients including intrahepatic (n = 155), proximal (n = 155) and distal (n = 126) cholangiocarcinoma by strict application of a combined immunohistochemical and in situ hybridization algorithm following the current guidelines for HER2 assessment in gastric cancer. \r\n\r\n Results: We identified a proportion of 1.4% (n = 6) patients that demonstrated HER2 gene amplification, with the highest rate among the distal cholangiocarcinoma patients (2.4%). None of the patients with equivocal (2+) immunohistochemical staining results exhibited gene amplification molecularly. In four of the five patients with HER2 positivity, gene amplification was already present in concomitantly tested high-grade biliary intraepithelial neoplasia (80%). HER2 gene amplification was not significantly associated with other clinical parameters, including survival. \r\n\r\n Conclusions: This study identifies HER2 gene amplification as a rare event in cholangiocarcinoma of the Western population, occurring already in high-grade BilIN in a subset of patients. Furthermore, we provide a robust testing algorithm that may be used prior to therapy administration in future clinical trials evaluating the role of HER2 as a predictive marker in cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"polo like kinase 2 mediator hedgehog survival signaling cholangiocarcinoma cells aim examine influence apoptotic mechanisms following inhibition polo like kinases therapeutically approach cholangiocellular cancer treatment methods cholangiocarcinomas chemotherapy resistant due mechanisms preventing tumor cell death investigated effect cisplatin cholangiocellular carcinoma cca cell lines kmch 1 mz ch 1 polo like kinases plk important regulators cell cycle inhibition discussed potential therapy plk inhibition regulate apoptotic mediators cells treated plk inhibitor bi6727 volasertib cisplatin combination compounds cell viability assessed mtt apoptosis measured dapi staining caspase 3 7 assay western blot qrt pcr used measure expression levels apoptosis related molecules bax bcl 2 results cell viability cca cell lines kmch 1 mz ch 1 reduced treatment conditions compared vehicle treated cells co treatment bi6727 cisplatin even enhance cytotoxic effect cisplatin single treatment thus co treatment cisplatin bi6727 slightly enhance cytotoxic effect cisplatin cell lines whereas evidence increased apoptosis induction solely mz ch 1 compared kmch 1 moreover plk inhibition decreases protein levels bcl 2 effect reversed proteasomal degradation inhibitor mg 132 contrast protein levels bax found altered plk inhibition findings indicate cytotoxic effects cisplatin mz ch 1 cells enhanced cotreatment bi6727 conclusion conclusion bi6727 treatment sensitize cca cells cisplatin induced apoptosis proteasomal bcl 2 degradation additional pro apoptotic effect stn","probabilities":0.9467213,"Title":"Polo-Like Kinase 2 Is A Mediator Of Hedgehog Survival Signaling In Cholangiocarcinoma Cells","Abstract":"Aim: To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment. \r\n\r\n Methods: As most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators. Here, cells were treated with PLK inhibitor BI6727 (Volasertib), Cisplatin, and in combination of both compounds. Cell viability was assessed by MTT; apoptosis was measured by DAPI staining and caspase-3/-7 assay. Western blot and qRT-PCR were used to measure expression levels of apoptosis-related molecules Bax and Bcl-2. \r\n\r\n Results: The cell viability in the CCA cell lines KMCH-1 and Mz-Ch-1 was reduced in all treatment conditions compared to vehicle-treated cells. Co-treatment with BI6727 and cisplatin could even enhance the cytotoxic effect of cisplatin single treatment. Thus, co-treatment of cisplatin with BI6727 could slightly enhance the cytotoxic effect of the cisplatin in both cell lines whereas there was evidence of increased apoptosis induction solely in Mz-Ch-1 as compared to KMCH-1. Moreover, PLK inhibition decreases protein levels of Bcl-2; an effect that can be reversed by the proteasomal degradation inhibitor MG-132. In contrast, protein levels of Bax were not found to be altered by PLK inhibition. These findings indicate that cytotoxic effects of Cisplatin in Mz-Ch-1 cells can be enhanced by cotreatment with BI6727. \r\n\r\n Conclusion: In conclusion, BI6727 treatment can sensitize CCA cells to cisplatin-induced apoptosis with proteasomal Bcl-2 degradation as an additional pro-apoptotic effect.","Source":"STN","category":"ANIMAL","training_data":"Polo-Like Kinase 2 Is A Mediator Of Hedgehog Survival Signaling In Cholangiocarcinoma Cells Aim: To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment. \r\n\r\n Methods: As most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators. Here, cells were treated with PLK inhibitor BI6727 (Volasertib), Cisplatin, and in combination of both compounds. Cell viability was assessed by MTT; apoptosis was measured by DAPI staining and caspase-3/-7 assay. Western blot and qRT-PCR were used to measure expression levels of apoptosis-related molecules Bax and Bcl-2. \r\n\r\n Results: The cell viability in the CCA cell lines KMCH-1 and Mz-Ch-1 was reduced in all treatment conditions compared to vehicle-treated cells. Co-treatment with BI6727 and cisplatin could even enhance the cytotoxic effect of cisplatin single treatment. Thus, co-treatment of cisplatin with BI6727 could slightly enhance the cytotoxic effect of the cisplatin in both cell lines whereas there was evidence of increased apoptosis induction solely in Mz-Ch-1 as compared to KMCH-1. Moreover, PLK inhibition decreases protein levels of Bcl-2; an effect that can be reversed by the proteasomal degradation inhibitor MG-132. In contrast, protein levels of Bax were not found to be altered by PLK inhibition. These findings indicate that cytotoxic effects of Cisplatin in Mz-Ch-1 cells can be enhanced by cotreatment with BI6727. \r\n\r\n Conclusion: In conclusion, BI6727 treatment can sensitize CCA cells to cisplatin-induced apoptosis with proteasomal Bcl-2 degradation as an additional pro-apoptotic effect. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic significance lymph node ratio resection peri hilar cholangiocarcinoma background lymph node ln metastases major negative prognostic factor peri hilar cholangiocarcinoma pcc prognostic significance extent ln dissection number metastatic ln lymph node ratio lnr still debate aims aims present study evaluate prognostic value ln status total number lns evaluated lnr pcc methods 1990 2008 62 patients pcc submitted surgical resection curative intent retrospectively evaluated number status harvested ln recorded results 53 patients 85 4 regional lymphadenectomy performed median number lns examined 7 range 1 25 median survival 41 9 months patients n0 compared 22 7 months 21 patients 39 6 n p 0 03 median survival 3 18 5 29 months patients 0 1 3 3 ln retrieved respectively p 0 01 five year survival patients lnr cut value 0 25 0 22 5 respectively p 0 03 conclusions ln metastases major prognostic factor survival surgical resection pcc number ln harvested lnr showed high prognostic value pubmed","probabilities":0.9799733,"Title":"Prognostic significance of lymph node ratio after resection of peri-hilar cholangiocarcinoma","Abstract":"BACKGROUND: Lymph node (LN) metastases are a major negative prognostic factor for peri-hilar cholangiocarcinoma (PCC). Prognostic significance of the extent of LN dissection, number of metastatic LN and the lymph node ratio (LNR) are still under debate. AIMS: The aims of the present study were to evaluate the prognostic value of the LN status, the total number of LNs evaluated and LNR in PCC. METHODS: Between 1990 and 2008, 62 patients with PCC submitted to surgical resection with curative intent were retrospectively evaluated. Number and status of harvested LN were recorded. RESULTS: In 53 patients (85.4%) regional lymphadenectomy was performed. Median number of LNs examined was 7 (range 1-25). Median survival was 41.9 months in patients with N0 compared with 22.7 months in 21 patients (39.6%) with N+ (P= 0.03). Median survival was 3, 18.5 and 29 months for patients with 0, 1-3 and >3 LN retrieved, respectively (P < 0.01). Five-year survival for patients above and below the LNR cut-off value of 0.25 was 0% and 22.5%, respectively (P= 0.03). CONCLUSIONS: LN metastases are a major prognostic factor for survival after surgical resection of PCC. The number of LN harvested and LNR showed high prognostic value.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of lymph node ratio after resection of peri-hilar cholangiocarcinoma BACKGROUND: Lymph node (LN) metastases are a major negative prognostic factor for peri-hilar cholangiocarcinoma (PCC). Prognostic significance of the extent of LN dissection, number of metastatic LN and the lymph node ratio (LNR) are still under debate. AIMS: The aims of the present study were to evaluate the prognostic value of the LN status, the total number of LNs evaluated and LNR in PCC. METHODS: Between 1990 and 2008, 62 patients with PCC submitted to surgical resection with curative intent were retrospectively evaluated. Number and status of harvested LN were recorded. RESULTS: In 53 patients (85.4%) regional lymphadenectomy was performed. Median number of LNs examined was 7 (range 1-25). Median survival was 41.9 months in patients with N0 compared with 22.7 months in 21 patients (39.6%) with N+ (P= 0.03). Median survival was 3, 18.5 and 29 months for patients with 0, 1-3 and >3 LN retrieved, respectively (P < 0.01). Five-year survival for patients above and below the LNR cut-off value of 0.25 was 0% and 22.5%, respectively (P= 0.03). CONCLUSIONS: LN metastases are a major prognostic factor for survival after surgical resection of PCC. The number of LN harvested and LNR showed high prognostic value. PubMed","prediction_labels":"HUMAN"},{"cleaned":"recurrent pyogenic cholangitis review imaging findings clinical management recurrent pyogenic cholangitis rpc infective process involving biliary tree typified pigmented intraductal calculi dilatation intra extrahepatic biliary tree previously endemic south east asia rpc seen western countries increasing access international travel immigration affected patients often plagued recurrent bouts cholangitis commonly suffer complications abscess formation biliary strictures severe cases cirrhosis portal hypertension may develop disease also known risk factor cholangiocarcinoma seen 5 affected patients exact etiology unknown parasitic infections clonorchis sinensis ascaris lumbricoides ascending bacterial infection gut flora escherichia coli low socioeconomic status associated strongly paper reviews imaging features disease well roles interventional radiology surgery respect management condition pubmed","probabilities":0.9799733,"Title":"Recurrent pyogenic cholangitis: a review of imaging findings and clinical management","Abstract":"Recurrent pyogenic cholangitis (RPC) is an infective process involving the biliary tree typified by pigmented intraductal calculi with dilatation of the intra- and extrahepatic biliary tree. Previously endemic to South-east Asia, RPC can now be seen in Western countries with the increasing access to international travel and immigration. Affected patients are often plagued by recurrent bouts of cholangitis, and commonly suffer from complications such as abscess formation and biliary strictures. In severe cases, cirrhosis with portal hypertension may develop. The disease is also a known risk factor for cholangiocarcinoma, and can be seen in up to 5% of affected patients. Its exact etiology is unknown, but parasitic infections such as Clonorchis sinensis and Ascaris lumbricoides, ascending bacterial infection with gut flora (Escherichia coli) and low socioeconomic status have been associated strongly with it. This paper reviews the imaging features of the disease, as well as the roles of interventional radiology and surgery with respect to management of the condition.","Source":"PubMed","category":"HUMAN","training_data":"Recurrent pyogenic cholangitis: a review of imaging findings and clinical management Recurrent pyogenic cholangitis (RPC) is an infective process involving the biliary tree typified by pigmented intraductal calculi with dilatation of the intra- and extrahepatic biliary tree. Previously endemic to South-east Asia, RPC can now be seen in Western countries with the increasing access to international travel and immigration. Affected patients are often plagued by recurrent bouts of cholangitis, and commonly suffer from complications such as abscess formation and biliary strictures. In severe cases, cirrhosis with portal hypertension may develop. The disease is also a known risk factor for cholangiocarcinoma, and can be seen in up to 5% of affected patients. Its exact etiology is unknown, but parasitic infections such as Clonorchis sinensis and Ascaris lumbricoides, ascending bacterial infection with gut flora (Escherichia coli) and low socioeconomic status have been associated strongly with it. This paper reviews the imaging features of the disease, as well as the roles of interventional radiology and surgery with respect to management of the condition. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term outcomes immunoglobulin g4 related sclerosing cholangitis 20 year retrospective cohort mayo clinic background immunoglobulin g4 related sclerosing cholangitis igg4 sc recognized worldwide however natural history long term outcomes well known methods retrospective single center cohort study identi ed patients received diagnosis igg4 sc mayo clinic rochester 1999 2018 diagnosis igg4 sc rigorously ascertained review medical records using validated hisort criteria comprehensive clinical data extracted patients charts long term outcomes interest included cirrhosis cholangiocarcinoma cca death compare outcomes random sample psc patients selected 1 1 ratio matched age diagnosis gender survival analyses performed comparisons using kaplan meier method log rank test cumulative incidence cirrhosis cca assessed using competing risks regression method results total 61 patients diagnosed igg4 sc study period median age diagnosis 66 years iqr 56 71 years 85 male median follow 6 1 years iqr 3 2 8 3 years pancreas commonly involved extra biliary organ 93 fifty ve patients received prednisone 96 experienced complete partial remission sixteen patients received rituximab maintenance therapy 88 maintained remission three patients 5 developed cirrhosis 2 patients 3 developed cca nine patients 15 died 2 due cirrhosis 2 due cca 1 due pancreatic cancer 4 due non hepatobiliary causes patients igg4 sc signi cantly lower 5 10 year cumulative incidence developing cirrhosis 5y 4 vs 34 10y 6 vs 43 p 0 001 cca 5y 3 vs 17 10y 4 vs 22 p 0 012 compared psc patients two patients psc group underwent liver transplantation none igg4 sc group overall 5 10 year survival greater igg4 sc cohort 5y 92 vs 70 10y 77 vs 57 p 0 02 conclusion patients igg4 sc majority received treatment small potential risk long term hepatobiliary complications risk cirrhosis cca death lower patients psc better outcome igg4 sc group likely due bene treatment surveillance population needs assessment especially subset receive respond treatment google scholar","probabilities":0.9799733,"Title":"Long-Term Outcomes Of Immunoglobulin G4-Related Sclerosing Cholangitis: A 20-Year Retrospective Cohort At Mayo Clinic","Abstract":"Background: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) has been recognized worldwide. However, its natural history and long-term outcomes are not well known. Methods: In this retrospective, single center, cohort study, we identied patients who received a diagnosis of IgG4-SC at Mayo Clinic Rochester from 1999 to 2018.The diagnosis of IgG4-SC was rigorously ascertained by review of medical records and using the validated HISORt criteria. Comprehensive clinical data was extracted from patients’ charts. Long-term outcomes of interest included cirrhosis, cholangiocarcinoma (CCA), and death. To compare outcomes, a random sample of PSC patients was selected in a 1:1 ratio matched for age of diagnosis and gender. Survival analyses were performed for comparisons using the Kaplan-Meier method, and log-rank test, and the cumulative incidence of cirrhosis and CCA was assessed using the competing risks regression method. Results: A total of 61 patients were diagnosed with IgG4-SC during the study period. The median age of diagnosis was 66 years (IQR: 56-71 years), 85% were male, and the median follow-up was 6.1 years (IQR: 3.2-8.3 years). The pancreas was the most commonly involved extra-biliary organ (93%). Fifty-ve patients received prednisone of whom 96% experienced complete or partial remission. Sixteen patients received rituximab as maintenance therapy, of whom 88% maintained remission. Three patients (5%) developed cirrhosis, and 2 patients (3%) developed CCA. Nine patients (15%) died; 2 due to cirrhosis, 2 due to CCA, 1 due to pancreatic cancer, and 4 due to non-hepatobiliary causes. Patients with IgG4-SC had signicantly lower 5- and 10-year cumulative incidence of developing cirrhosis (5y: 4% vs. 34%10y: 6% vs. 43%; P<0.001) and CCA (5y: 3% vs. 17%; 10y: 4% vs. 22%; P=0.012) compared with PSC patients. Two patients in the PSC group underwent liver transplantation, while none in the IgG4-SC group. Overall 5- and 10-year survival was greater in the IgG4-SC cohort (5y: 92% vs. 70%; 10y: 77% vs. 57%; P=0.02. Conclusion: Patients with IgG4-SC, the majority of whom received treatment, have a small potential risk of long-term hepatobiliary complications. Their risk of cirrhosis, CCA and death, was lower than in patients with PSC. The better outcome in the IgG4-SC group is likely due to the benet of treatment. Surveillance in this population needs further assessment, especially the subset that does receive or respond to treatment","Source":"Google Scholar","category":"HUMAN","training_data":"Long-Term Outcomes Of Immunoglobulin G4-Related Sclerosing Cholangitis: A 20-Year Retrospective Cohort At Mayo Clinic Background: Immunoglobulin G4-related sclerosing cholangitis (IgG4-SC) has been recognized worldwide. However, its natural history and long-term outcomes are not well known. Methods: In this retrospective, single center, cohort study, we identied patients who received a diagnosis of IgG4-SC at Mayo Clinic Rochester from 1999 to 2018.The diagnosis of IgG4-SC was rigorously ascertained by review of medical records and using the validated HISORt criteria. Comprehensive clinical data was extracted from patients’ charts. Long-term outcomes of interest included cirrhosis, cholangiocarcinoma (CCA), and death. To compare outcomes, a random sample of PSC patients was selected in a 1:1 ratio matched for age of diagnosis and gender. Survival analyses were performed for comparisons using the Kaplan-Meier method, and log-rank test, and the cumulative incidence of cirrhosis and CCA was assessed using the competing risks regression method. Results: A total of 61 patients were diagnosed with IgG4-SC during the study period. The median age of diagnosis was 66 years (IQR: 56-71 years), 85% were male, and the median follow-up was 6.1 years (IQR: 3.2-8.3 years). The pancreas was the most commonly involved extra-biliary organ (93%). Fifty-ve patients received prednisone of whom 96% experienced complete or partial remission. Sixteen patients received rituximab as maintenance therapy, of whom 88% maintained remission. Three patients (5%) developed cirrhosis, and 2 patients (3%) developed CCA. Nine patients (15%) died; 2 due to cirrhosis, 2 due to CCA, 1 due to pancreatic cancer, and 4 due to non-hepatobiliary causes. Patients with IgG4-SC had signicantly lower 5- and 10-year cumulative incidence of developing cirrhosis (5y: 4% vs. 34%10y: 6% vs. 43%; P<0.001) and CCA (5y: 3% vs. 17%; 10y: 4% vs. 22%; P=0.012) compared with PSC patients. Two patients in the PSC group underwent liver transplantation, while none in the IgG4-SC group. Overall 5- and 10-year survival was greater in the IgG4-SC cohort (5y: 92% vs. 70%; 10y: 77% vs. 57%; P=0.02. Conclusion: Patients with IgG4-SC, the majority of whom received treatment, have a small potential risk of long-term hepatobiliary complications. Their risk of cirrhosis, CCA and death, was lower than in patients with PSC. The better outcome in the IgG4-SC group is likely due to the benet of treatment. Surveillance in this population needs further assessment, especially the subset that does receive or respond to treatment Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"increasing survival patients cholangiocarcinoma last decade population based study introduction cholangiocarcinoma carries increased morbidity mortality aim study investigate survival intrahepatic extrahepatic cholangiocarcinoma 40 year period also identify risk factors associated increased mortality methods conducted analysis using surveillance epidemiology end results seer cancer registry large population based survey national institutes health inclusion criteria included histologically confirmed cholangiocarcinoma 1973 2013 localized either intra extrahepatic bile ducts results total 10 829 patients diagnosed primary cholangiocarcinoma 40 year study period 6 892 63 6 intrahepatic 3 937 36 4 extrahepatic origin patient demographics include mean age 66 8 years sem 0 124 range 11 99 78 white 7 5 black 14 3 unknown 53 male 4 963 46 patients staging available 27 6 localized 33 3 regional 39 1 distally located extrahepatic cholangiocarcinoma better survival intrahepatic cancers median time survival entire study cohort 11 0 months 25th 75th 4 0 29 0 months including 10 0 months 4 0 30 months intrahepatic 12 0 months 5 0 28 0 months extrahepatic malignancies p 0 003 cox proportional hazards modeling revealed age hazard ratio hr 1 009 95 ci 1 005 1 014 black race hr 1 326 ci 1 071 1 642 female gender hr 0 866 ci 0 773 0 971 year diagnosis hr 0 953 ci 0 941 0 966 grade hr 1 363 ci 1 256 1 479 stage hr 1 872 ci 1 737 2 018 significantly affected survival pp 0 824 increase survival last 4 decades especially last decade figure 1 conclusion increased survival intrahepatic extrahepatic cholangiocarcinomas observed last decade least partially related surgery radiation however survival time remains dismal advanced age black race male gender advanced grade stage disease associated decreased survival efforts focus strategies earlier diagnosis patients risk developing bile duct malignancies google scholar","probabilities":0.9799733,"Title":"Increasing Survival Of Patients With Cholangiocarcinoma In The Last Decade: A Population-Based Study","Abstract":"Introduction: Cholangiocarcinoma carries increased morbidity and mortality. The aim of the study was to investigate the survival of intrahepatic and extrahepatic cholangiocarcinoma over a 40-year period and also to identify any risk factors associated with increased mortality.\nMethods: We conducted an analysis using the Surveillance Epidemiology & End Results (SEER) Cancer registry, a large, population-based survey from the National Institutes of Health. Inclusion criteria included histologically confirmed cholangiocarcinoma between 1973-2013 and localized to either intra or extrahepatic bile ducts.\nResults: A total of 10,829 patients were diagnosed with primary cholangiocarcinoma during the 40-year study period, of which 6,892 (63.6%) were intrahepatic and 3,937 (36.4%) were extrahepatic in origin. Patient demographics include mean age: 66.8 years (SEM: 0.124; range: 11-99), 78% white (7.5% black, 14.3% other/unknown) and 53% male. Of 4,963 (46%) patients with staging available, 27.6% were localized, 33.3% were regional and 39.1% were distally located. Extrahepatic cholangiocarcinoma had better survival than intrahepatic cancers. Median time of survival for the entire study cohort was 11.0 months (25th-75th %: 4.0-29.0 months), including 10.0 months (4.0-30 months) for intrahepatic and 12.0 months (5.0-28.0 months) for extrahepatic malignancies (P=0.003). Cox proportional hazards modeling revealed age (hazard ratio [HR]: 1.009; 95% CI: 1.005-1.014), black race (HR: 1.326; CI: 1.071-1.642), female gender (HR: 0.866; CI: 0.773-0.971), year of diagnosis (HR: 0.953; CI: 0.941-0.966), grade (HR: 1.363; CI: 1.256-1.479) and stage (HR: 1.872; CI: 1.737-2.018) significantly affected survival (all PP=0.824). There has been an increase in survival in over the last 4 decades especially in the last decade (Figure 1).\nConclusion: Increased survival in intrahepatic and extrahepatic cholangiocarcinomas observed over the last decade, which is at least partially related to surgery and radiation, however, survival time remains dismal. Advanced age, black race, male gender and advanced grade and stage of disease were associated with decreased survival. Efforts should focus on strategies for earlier diagnosis in patients at risk for developing bile duct malignancies.","Source":"Google Scholar","category":"HUMAN","training_data":"Increasing Survival Of Patients With Cholangiocarcinoma In The Last Decade: A Population-Based Study Introduction: Cholangiocarcinoma carries increased morbidity and mortality. The aim of the study was to investigate the survival of intrahepatic and extrahepatic cholangiocarcinoma over a 40-year period and also to identify any risk factors associated with increased mortality.\nMethods: We conducted an analysis using the Surveillance Epidemiology & End Results (SEER) Cancer registry, a large, population-based survey from the National Institutes of Health. Inclusion criteria included histologically confirmed cholangiocarcinoma between 1973-2013 and localized to either intra or extrahepatic bile ducts.\nResults: A total of 10,829 patients were diagnosed with primary cholangiocarcinoma during the 40-year study period, of which 6,892 (63.6%) were intrahepatic and 3,937 (36.4%) were extrahepatic in origin. Patient demographics include mean age: 66.8 years (SEM: 0.124; range: 11-99), 78% white (7.5% black, 14.3% other/unknown) and 53% male. Of 4,963 (46%) patients with staging available, 27.6% were localized, 33.3% were regional and 39.1% were distally located. Extrahepatic cholangiocarcinoma had better survival than intrahepatic cancers. Median time of survival for the entire study cohort was 11.0 months (25th-75th %: 4.0-29.0 months), including 10.0 months (4.0-30 months) for intrahepatic and 12.0 months (5.0-28.0 months) for extrahepatic malignancies (P=0.003). Cox proportional hazards modeling revealed age (hazard ratio [HR]: 1.009; 95% CI: 1.005-1.014), black race (HR: 1.326; CI: 1.071-1.642), female gender (HR: 0.866; CI: 0.773-0.971), year of diagnosis (HR: 0.953; CI: 0.941-0.966), grade (HR: 1.363; CI: 1.256-1.479) and stage (HR: 1.872; CI: 1.737-2.018) significantly affected survival (all PP=0.824). There has been an increase in survival in over the last 4 decades especially in the last decade (Figure 1).\nConclusion: Increased survival in intrahepatic and extrahepatic cholangiocarcinomas observed over the last decade, which is at least partially related to surgery and radiation, however, survival time remains dismal. Advanced age, black race, male gender and advanced grade and stage of disease were associated with decreased survival. Efforts should focus on strategies for earlier diagnosis in patients at risk for developing bile duct malignancies. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"importance choice resection procedures t1 t2 stage carcinoma ampulla vater purpose ampulla vater av strategic location remarkable predisposition development various malignant tumors makes challenging surgery study aimed examine prognostic factors treatment early stage carcinoma av well contribute choice optimal surgical procedure methods analyzed 109 av patients hospitalized clinical center serbia january 1999 december 2008 compared clinicopathological features analyzed intra postoperative data recurrences survival according duodenopancreatectomy dp local resection lr results dp performed 83 lr 26 patients overall survival os significantly influenced pathological p tumor stage pt1 t2 vs pt3 t4 pathological nodal stage pn0 vs pn1 perineural vascular invasion grade tumor differentiation g1 vs g3 resection margin status r0 vs r1 kaplan meier analysis showed 64 5 year overall survival patients pt1 t2 stage group dp 58 group lr p 0 05 survival analysis pn1 patients two groups showed statistically significant difference dp 49 67 vs lr 28 68 months p 0 05 postoperative complications occurred frequently patients treated dp compared lr tumor recurrence occurred 23 07 lr patients 4 0 dp patients pt1 t2 stage rate hospital mortality significantly different dp 9 78 vs lr 0 patients p 0 05 conclusion resection mandatory proven av tumors dp treatment choice lr due reduced morbidity mortality might recommended elderly patients comorbidities patients stage pt1 t2 pn0 well differentiated g1 g2 tumors pubmed","probabilities":0.9799733,"Title":"The importance of choice of resection procedures in T1 and T2 stage of carcinoma of the ampulla of Vater","Abstract":"PURPOSE: The ampulla of Vater (AV), with its strategic location and its remarkable predisposition to the development of various malignant tumors, makes it very challenging for surgery. In this study we aimed to examine the prognostic factors in the treatment of early-stage carcinoma of the AV as well as to contribute to the choice of optimal surgical procedure. METHODS: We analyzed 109 AV patients, hospitalized at the Clinical Center of Serbia from January 1999 to December 2008 and we compared the clinicopathological features, analyzed intra- and postoperative data, recurrences and survival, according to duodenopancreatectomy (DP) or local resection (LR). RESULTS: DP was performed in 83 and LR in 26 patients. Overall survival (OS) was significantly influenced by the pathological (p) tumor stage (pT1/T2 vs pT3/T4), pathological nodal stage (pN0 vs pN1), perineural and vascular invasion, grade of tumor differentiation (G1 vs G3), and resection margin status (R0 vs R1). Kaplan-Meier analysis showed 64% 5-year overall survival of patients with pT1/T2 stage in the group with DP, and 58% in the group with LR (p>0.05). Survival analysis of pN1 patients in these two groups showed statistically significant difference (DP 49.67 vs LR 28.68 months, p<0.05). Postoperative complications occurred more frequently in patients treated with DP, compared with LR. Tumor recurrence occurred in 23.07% of LR patients and in 4.0% of DP patients, in pT1/T2 stage. The rate of in-hospital mortality was not significantly different in DP (9.78%) vs LR (0%) patients (p>0.05). CONCLUSION: Resection is mandatory for all proven AV tumors, and DP is the treatment choice. LR, due to reduced morbidity and mortality, might be recommended in elderly patients with comorbidities and in patients with stage pT1/T2, pN0 and well differentiated (G1,G2) tumors.","Source":"PubMed","category":"HUMAN","training_data":"The importance of choice of resection procedures in T1 and T2 stage of carcinoma of the ampulla of Vater PURPOSE: The ampulla of Vater (AV), with its strategic location and its remarkable predisposition to the development of various malignant tumors, makes it very challenging for surgery. In this study we aimed to examine the prognostic factors in the treatment of early-stage carcinoma of the AV as well as to contribute to the choice of optimal surgical procedure. METHODS: We analyzed 109 AV patients, hospitalized at the Clinical Center of Serbia from January 1999 to December 2008 and we compared the clinicopathological features, analyzed intra- and postoperative data, recurrences and survival, according to duodenopancreatectomy (DP) or local resection (LR). RESULTS: DP was performed in 83 and LR in 26 patients. Overall survival (OS) was significantly influenced by the pathological (p) tumor stage (pT1/T2 vs pT3/T4), pathological nodal stage (pN0 vs pN1), perineural and vascular invasion, grade of tumor differentiation (G1 vs G3), and resection margin status (R0 vs R1). Kaplan-Meier analysis showed 64% 5-year overall survival of patients with pT1/T2 stage in the group with DP, and 58% in the group with LR (p>0.05). Survival analysis of pN1 patients in these two groups showed statistically significant difference (DP 49.67 vs LR 28.68 months, p<0.05). Postoperative complications occurred more frequently in patients treated with DP, compared with LR. Tumor recurrence occurred in 23.07% of LR patients and in 4.0% of DP patients, in pT1/T2 stage. The rate of in-hospital mortality was not significantly different in DP (9.78%) vs LR (0%) patients (p>0.05). CONCLUSION: Resection is mandatory for all proven AV tumors, and DP is the treatment choice. LR, due to reduced morbidity and mortality, might be recommended in elderly patients with comorbidities and in patients with stage pT1/T2, pN0 and well differentiated (G1,G2) tumors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"update diagnosis treatment cholangiocarcinoma purpose review cholangiocarcinoma rare biliary adenocarcinoma associated poor outcomes cholangiocarcinoma subdivided extrahepatic intrahepatic variants intrahepatic cholangiocarcinoma differentiated 1 peripheral mass forming tumors 2 central periductal infiltrating tumors aimed review currently known risk factors diagnostic tools treatment options well highlight need clinical trials research improve overall survival rates recent findings cholangiocarcinoma seen significant increase incidence rates last several decades patients carry documented risk factors include infections inflammatory conditions cholangiocarcinoma typically forms setting cholestasis chronic inflammation management strategies include multispecialty treatments consideration surgical resection systemic chemotherapy targeted radiation therapy surgically resectable disease curable treatment option may involve liver transplantation certain selected cases referrals centers excellence along enrollment novel clinical trials recommended patients unresectable recurrent disease article provides overview cholangiocarcinoma discusses current diagnosis treatment options incidence increasing risk factors discovered much work remains improve outcomes ominous disease pubmed","probabilities":0.9799733,"Title":"Update on the Diagnosis and Treatment of Cholangiocarcinoma","Abstract":"PURPOSE OF REVIEW: Cholangiocarcinoma is a rare biliary adenocarcinoma associated with poor outcomes. Cholangiocarcinoma is subdivided into extrahepatic and intrahepatic variants. Intrahepatic cholangiocarcinoma is then further differentiated into (1) peripheral mass-forming tumors and (2) central periductal infiltrating tumors. We aimed to review the currently known risk factors, diagnostic tools, and treatment options, as well as highlight the need for further clinical trials and research to improve overall survival rates. RECENT FINDINGS: Cholangiocarcinoma has seen significant increase in incidence rates over the last several decades. Most patients do not carry the documented risk factors, which include infections and inflammatory conditions, but cholangiocarcinoma typically forms in the setting of cholestasis and chronic inflammation. Management strategies include multispecialty treatments, with consideration of surgical resection, systemic chemotherapy, and targeted radiation therapy. Surgically resectable disease is the only curable treatment option, which may involve liver transplantation in certain selected cases. Referrals to centers of excellence, along with enrollment in novel clinical trials are recommended for patients with unresectable or recurrent disease. This article provides an overview of cholangiocarcinoma and discusses the current diagnosis and treatment options. While incidence is increasing and more risk factors are being discovered, much more work remains to improve outcomes of this ominous disease.","Source":"PubMed","category":"HUMAN","training_data":"Update on the Diagnosis and Treatment of Cholangiocarcinoma PURPOSE OF REVIEW: Cholangiocarcinoma is a rare biliary adenocarcinoma associated with poor outcomes. Cholangiocarcinoma is subdivided into extrahepatic and intrahepatic variants. Intrahepatic cholangiocarcinoma is then further differentiated into (1) peripheral mass-forming tumors and (2) central periductal infiltrating tumors. We aimed to review the currently known risk factors, diagnostic tools, and treatment options, as well as highlight the need for further clinical trials and research to improve overall survival rates. RECENT FINDINGS: Cholangiocarcinoma has seen significant increase in incidence rates over the last several decades. Most patients do not carry the documented risk factors, which include infections and inflammatory conditions, but cholangiocarcinoma typically forms in the setting of cholestasis and chronic inflammation. Management strategies include multispecialty treatments, with consideration of surgical resection, systemic chemotherapy, and targeted radiation therapy. Surgically resectable disease is the only curable treatment option, which may involve liver transplantation in certain selected cases. Referrals to centers of excellence, along with enrollment in novel clinical trials are recommended for patients with unresectable or recurrent disease. This article provides an overview of cholangiocarcinoma and discusses the current diagnosis and treatment options. While incidence is increasing and more risk factors are being discovered, much more work remains to improve outcomes of this ominous disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"investigation targetable predictive prognostic markers gallbladder carcinoma background gallbladder carcinoma uncommon world frequent south east asia presents advanced stages limited therapeutic options investigated targetable predictive prognostic markers 268 cases including 233 primary site lesions 35 metastatic gallbladder carcinoma methods egfr vegf her2 neu p53 assessed using immunohistochemistry her2 neu validated subset fluorescent situ hybridization fish using tissue microarray tma broader spectrum gene variation screened ngs representative ffpe tissue using ion ampliseq cancer hotspot panel v2 results mean age 49 5 years female predominance 77 6 histological types included 221 cases adenocarcinoma otherwise specified nos 23 invasive papillary carcinoma 11 mucinous adenocarcinoma 8 adenosquamous 1 signet ring 3 neuroendocrine 1 undifferentiated carcinoma majority 76 1 presented stage 3 4 disease overall positive expression p53 44 8 vegf 79 4 her2 neu 27 3 egfr 34 6 intratumoral heterogeneity evident her2 neu marker expression significantly associated stage grade type metastasis except vegf correlated histological type p 0 018 tumor grade p 0 027 ngs using ion ampliseq cancer hotspot panel v2 revealed multiple non synonymous mutations frequent tp53 cdkn2a mutations mutations met kdr pik3ca vhl mpl her2 smarcb1 genes conclusions predictive targetable markers like her2 neu vegf egfr expressed high proportion gallbladder carcinoma significant expression ras pathway molecules suggests interactions take place among different members erbb family tumor development google scholar","probabilities":0.7966102,"Title":"Investigation Of Targetable Predictive And Prognostic Markers In Gallbladder Carcinoma","Abstract":"Background\nGallbladder carcinoma, uncommon in most of the world, is frequent in South East Asia. It presents in advanced stages with limited therapeutic options. We investigated targetable predictive and prognostic Markers in 268 cases including 233 primary site lesions and 35 metastatic gallbladder carcinoma.\nMethods\nEGFR, VEGF, HER2/Neu and p53 were assessed using immunohistochemistry. HER2/Neu was validated in a subset by fluorescent in situ hybridization (FISH) using tissue microarray (TMA). Broader spectrum of gene variation was screened in NGS in representative FFPE tissue using the Ion AmpliSeq cancer hotspot panel V2.\nResults\nMean age was 49.5 years with female predominance (77.6%). Histological types included 221 cases of adenocarcinoma not otherwise specified (NOS), 23 invasive papillary carcinoma, 11 mucinous adenocarcinoma, 8 adenosquamous, 1 signet ring, 3 neuroendocrine and 1 undifferentiated carcinoma. Majority (76.1%) presented with stage 3/4 disease. Overall positive expression of p53 was 44.8%, VEGF 79.4%, HER2/Neu 27.3% and EGFR 34.6%. Intratumoral heterogeneity was evident in HER2/Neu. Marker expression was not significantly associated with stage, grade, type and metastasis except VEGF which correlated with histological type (P=0.018) and tumor grade (P=0.027). NGS using Ion AmpliSeq cancer hotspot panel V2 revealed multiple non synonymous mutations, most frequent being TP53 and CDKN2A mutations and mutations in MET, KDR, PIK3CA, VHL, MPL, HER2 and SMARCB1 genes.\nConclusions\nPredictive targetable markers like HER2/Neu, VEGF and EGFR are expressed in high proportion of gallbladder carcinoma. Significant expression of RAS pathway molecules suggests that interactions take place among the different members of the ErbB family during tumor development.","Source":"Google Scholar","category":"HUMAN","training_data":"Investigation Of Targetable Predictive And Prognostic Markers In Gallbladder Carcinoma Background\nGallbladder carcinoma, uncommon in most of the world, is frequent in South East Asia. It presents in advanced stages with limited therapeutic options. We investigated targetable predictive and prognostic Markers in 268 cases including 233 primary site lesions and 35 metastatic gallbladder carcinoma.\nMethods\nEGFR, VEGF, HER2/Neu and p53 were assessed using immunohistochemistry. HER2/Neu was validated in a subset by fluorescent in situ hybridization (FISH) using tissue microarray (TMA). Broader spectrum of gene variation was screened in NGS in representative FFPE tissue using the Ion AmpliSeq cancer hotspot panel V2.\nResults\nMean age was 49.5 years with female predominance (77.6%). Histological types included 221 cases of adenocarcinoma not otherwise specified (NOS), 23 invasive papillary carcinoma, 11 mucinous adenocarcinoma, 8 adenosquamous, 1 signet ring, 3 neuroendocrine and 1 undifferentiated carcinoma. Majority (76.1%) presented with stage 3/4 disease. Overall positive expression of p53 was 44.8%, VEGF 79.4%, HER2/Neu 27.3% and EGFR 34.6%. Intratumoral heterogeneity was evident in HER2/Neu. Marker expression was not significantly associated with stage, grade, type and metastasis except VEGF which correlated with histological type (P=0.018) and tumor grade (P=0.027). NGS using Ion AmpliSeq cancer hotspot panel V2 revealed multiple non synonymous mutations, most frequent being TP53 and CDKN2A mutations and mutations in MET, KDR, PIK3CA, VHL, MPL, HER2 and SMARCB1 genes.\nConclusions\nPredictive targetable markers like HER2/Neu, VEGF and EGFR are expressed in high proportion of gallbladder carcinoma. Significant expression of RAS pathway molecules suggests that interactions take place among the different members of the ErbB family during tumor development. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"nsaid use risk hepatocellular carcinoma intrahepatic cholangiocarcinoma liver cancer pooling project chronic inflammation plays pivotal role pathogenesis hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc two common types liver cancer number prior experimental studies suggested nonsteroidal anti inflammatory drugs nsaids including aspirin ibuprofen may potentially protect liver cancer however observational study examined association aspirin duration dose counter non aspirin nsaids ibuprofen liver cancer incidence furthermore association nsaid use risk icc unclear part liver cancer pooling project harmonized data 1 084 133 individuals hcc 679 icc 225 10 u based prospective cohort studies cox proportional hazards regression models used evaluate multivariable adjusted hrs 95 confidence intervals ci current aspirin use versus nonuse inversely associated hcc hr 0 68 95 ci 0 57 0 81 persisted restricted individuals using non aspirin nsaids 5 10 year lag analysis association aspirin use hcc risk stronger users reported daily use longer duration use lower dosage ibuprofen use associated hcc risk aspirin use associated reduced icc risk men hr 0 64 95 ci 0 42 0 98 women hr 1 34 95 ci 0 89 2 01 p interaction 0 01 observed inverse association aspirin use liver cancer study together previous data suggests merit future intervention studies aspirin agents affect chronic inflammatory pathways hcc possibly icc pubmed","probabilities":0.9799733,"Title":"NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project","Abstract":"Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC.","Source":"PubMed","category":"HUMAN","training_data":"NSAID Use and Risk of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma: The Liver Cancer Pooling Project Chronic inflammation plays a pivotal role in the pathogenesis of hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), the two most common types of liver cancer. A number of prior experimental studies have suggested that nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin and ibuprofen, may potentially protect against liver cancer. However, no observational study has examined the association between aspirin duration and dose or other over-the-counter non-aspirin NSAIDs, such as ibuprofen, and liver cancer incidence. Furthermore, the association between NSAID use and risk of ICC is unclear. As part of the Liver Cancer Pooling Project, we harmonized data on 1,084,133 individuals (HCC = 679, ICC = 225) from 10 U.S.-based prospective cohort studies. Cox proportional hazards regression models were used to evaluate multivariable-adjusted HRs and 95% confidence intervals (CI). Current aspirin use, versus nonuse, was inversely associated with HCC (HR, 0.68; 95% CI, 0.57-0.81), which persisted when restricted to individuals not using non-aspirin NSAIDs and in a 5- and 10-year lag analysis. The association between aspirin use and HCC risk was stronger for users who reported daily use, longer duration use, and lower dosage. Ibuprofen use was not associated with HCC risk. Aspirin use was associated with a reduced ICC risk in men (HR, 0.64; 95% CI, 0.42-0.98) but not women (HR, 1.34; 95% CI, 0.89-2.01; P(interaction) = 0.01). The observed inverse association between aspirin use and liver cancer in our study, together with previous data, suggests the merit of future intervention studies of aspirin and other agents that affect chronic inflammatory pathways for HCC and possibly ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"shmt2 overexpression predicts poor prognosis intrahepatic cholangiocarcinoma background objective serine hydroxymethyltransferase 2 shmt2 functions key enzyme serine glycine biosynthesis one carbon metabolism recent studies shown shmt2 participated tumor growth progression variety cancer types objective present study explore expression shmt2 evaluate prognostic value patients intrahepatic cholangiocarcinoma icca patients methods retrospectively investigated expression shmt2 100 primary icca samples immunohistochemical ihc staining tissue array results high shmt2 expression found 52 100 specimens results indicated shmt2 level upregulated compared adjacent nontumor intrahepatic bile duct tissue furthermore shmt2 level closely associated tumor stage p 0 017 tumor tnm stage p 0 041 patients icca age gender tumor size tumor number pathological grade vascular invasion n stage moreover kaplan meier analysis suggested patients lower shmt2 level longer survival rate high expression 45 8 vs 23 1 p 0 030 additionally multivariate analysis model indicated shmt2 independent adverse prognosticator icca conclusion high shmt2 level correlated poorer overall survival patients icca shmt2 proved powerful independent prognostic factor potential therapeutic target patients icca stn","probabilities":0.7966102,"Title":"Shmt2 Overexpression Predicts Poor Prognosis In Intrahepatic Cholangiocarcinoma","Abstract":"Background and objective: Serine hydroxymethyltransferase 2 (SHMT2) functions as a key enzyme in serine/glycine biosynthesis and one-carbon metabolism. Recent studies have shown that SHMT2 participated in tumor growth and progression in a variety of cancer types. The objective of the present study is to explore the expression of SHMT2 and evaluate its prognostic value in patients with intrahepatic cholangiocarcinoma (iCCA). \r\n\r\n Patients and methods: We retrospectively investigated the expression of SHMT2 in 100 primary iCCA samples through immunohistochemical (IHC) staining on a tissue array. \r\n\r\n Results: High SHMT2 expression was found in 52 of the 100 specimens. The results indicated that SHMT2 level was upregulated compared to adjacent nontumor intrahepatic bile duct tissue. Furthermore, SHMT2 level was closely associated with tumor T stage (P = 0.017) and tumor TNM stage (P = 0.041) in patients with iCCA, but not with age, gender, tumor size, tumor number, pathological grade, vascular invasion, or N stage. Moreover, Kaplan-Meier analysis suggested that patients with lower SHMT2 level have longer survival rate than those with high expression (45.8 vs 23.1%, P = 0.030). Additionally, the multivariate analysis model indicated SHMT2 is an independent adverse prognosticator in iCCA. \r\n\r\n Conclusion: High SHMT2 level was correlated with poorer overall survival in patients with iCCA. SHMT2 was proved to be a powerful and independent prognostic factor and a potential therapeutic target for patients with iCCA.","Source":"STN","category":"HUMAN","training_data":"Shmt2 Overexpression Predicts Poor Prognosis In Intrahepatic Cholangiocarcinoma Background and objective: Serine hydroxymethyltransferase 2 (SHMT2) functions as a key enzyme in serine/glycine biosynthesis and one-carbon metabolism. Recent studies have shown that SHMT2 participated in tumor growth and progression in a variety of cancer types. The objective of the present study is to explore the expression of SHMT2 and evaluate its prognostic value in patients with intrahepatic cholangiocarcinoma (iCCA). \r\n\r\n Patients and methods: We retrospectively investigated the expression of SHMT2 in 100 primary iCCA samples through immunohistochemical (IHC) staining on a tissue array. \r\n\r\n Results: High SHMT2 expression was found in 52 of the 100 specimens. The results indicated that SHMT2 level was upregulated compared to adjacent nontumor intrahepatic bile duct tissue. Furthermore, SHMT2 level was closely associated with tumor T stage (P = 0.017) and tumor TNM stage (P = 0.041) in patients with iCCA, but not with age, gender, tumor size, tumor number, pathological grade, vascular invasion, or N stage. Moreover, Kaplan-Meier analysis suggested that patients with lower SHMT2 level have longer survival rate than those with high expression (45.8 vs 23.1%, P = 0.030). Additionally, the multivariate analysis model indicated SHMT2 is an independent adverse prognosticator in iCCA. \r\n\r\n Conclusion: High SHMT2 level was correlated with poorer overall survival in patients with iCCA. SHMT2 was proved to be a powerful and independent prognostic factor and a potential therapeutic target for patients with iCCA. STN","prediction_labels":"HUMAN"},{"cleaned":"initial outcome selective intraarterial radionuclide therapy yttrium 90 microspheres salvage therapy unresectable metastatic liver disease purpose aim study retrospectively evaluate potential benefit survival outcomes selective intraarterial radionuclide therapy sirt yttrium 90 microspheres salvage therapy liver metastasis different tumors material methods sixty one patients unresectable liver metastases colorectal carcinoma n 23 neuroendocrine tumor net n 12 cholangiocarcinoma n 9 others n 17 received yttrium 90 microspheres patients treated salvage setting 11 month mean follow early metabolic treatment response evaluated 18f fluorodeoxyglucose positron emission tomography fdg pet ct sixth week treatment results 61 patients 32 alive end study median overall survival os 17 0 2 5 months 95 confidence interval 11 9 22 0 subset analysis colorectal noncolorectal groups demonstrated median os rates 14 0 5 8 17 0 4 8 months respectively p 0 543 mean os patients net cholangiocarcinoma 29 0 3 1 months 17 7 3 2 months respectively p 0 010 according early metabolic treatment response mean os responder nonresponder groups 32 0 5 6 months 11 4 2 1 months respectively p 0 054 eastern cooperative oncology group performance status 1 p 0 018 chemotherapy naive patients p 0 008 showed significant correlation survival conclusion sirt effective treatment option patients metastatic liver disease salvage setting acceptable toxicity pubmed","probabilities":0.9799733,"Title":"Initial outcome after selective intraarterial radionuclide therapy with yttrium-90 microspheres as salvage therapy for unresectable metastatic liver disease","Abstract":"PURPOSE: The aim of the study was to retrospectively evaluate the potential benefit on survival outcomes of selective intraarterial radionuclide therapy (SIRT) with Yttrium-90 microspheres as a salvage therapy in liver metastasis of different tumors. MATERIAL AND METHODS: Sixty-one patients who had unresectable liver metastases from colorectal carcinoma (n=23), neuroendocrine tumor (NET; n=12), cholangiocarcinoma (n=9), and others (n=17) received yttrium-90 microspheres. All patients were treated in a salvage setting with an 11-month mean follow-up. Early metabolic treatment response was evaluated by 18F-Fluorodeoxyglucose positron emission tomography (FDG PET-CT) in the sixth week after treatment. RESULTS: Of the 61 patients, 32 were alive at the end of the study; median overall survival (OS) was 17.0 ± 2.5 months (95% confidence interval: 11.9-22.0). A subset analysis of colorectal and noncolorectal groups demonstrated median OS rates of 14.0 ± 5.8 and 17.0 ± 4.8 months, respectively (p=0.543). The mean OS for patients with NET and cholangiocarcinoma was 29.0 ± 3.1 months and 17.7 ± 3.2 months, respectively (p=0.010). According to the early metabolic treatment response, the mean OS of responder and nonresponder groups was 32.0 ± 5.6 months and 11.4 ± 2.1 months, respectively (p=0.054). Eastern Cooperative Oncology Group performance status <1 (p=0.018) and chemotherapy-naive patients (p=0.008) showed significant correlation with survival. CONCLUSION: SIRT is an effective treatment option for patients with metastatic liver disease in a salvage setting with acceptable toxicity.","Source":"PubMed","category":"HUMAN","training_data":"Initial outcome after selective intraarterial radionuclide therapy with yttrium-90 microspheres as salvage therapy for unresectable metastatic liver disease PURPOSE: The aim of the study was to retrospectively evaluate the potential benefit on survival outcomes of selective intraarterial radionuclide therapy (SIRT) with Yttrium-90 microspheres as a salvage therapy in liver metastasis of different tumors. MATERIAL AND METHODS: Sixty-one patients who had unresectable liver metastases from colorectal carcinoma (n=23), neuroendocrine tumor (NET; n=12), cholangiocarcinoma (n=9), and others (n=17) received yttrium-90 microspheres. All patients were treated in a salvage setting with an 11-month mean follow-up. Early metabolic treatment response was evaluated by 18F-Fluorodeoxyglucose positron emission tomography (FDG PET-CT) in the sixth week after treatment. RESULTS: Of the 61 patients, 32 were alive at the end of the study; median overall survival (OS) was 17.0 ± 2.5 months (95% confidence interval: 11.9-22.0). A subset analysis of colorectal and noncolorectal groups demonstrated median OS rates of 14.0 ± 5.8 and 17.0 ± 4.8 months, respectively (p=0.543). The mean OS for patients with NET and cholangiocarcinoma was 29.0 ± 3.1 months and 17.7 ± 3.2 months, respectively (p=0.010). According to the early metabolic treatment response, the mean OS of responder and nonresponder groups was 32.0 ± 5.6 months and 11.4 ± 2.1 months, respectively (p=0.054). Eastern Cooperative Oncology Group performance status <1 (p=0.018) and chemotherapy-naive patients (p=0.008) showed significant correlation with survival. CONCLUSION: SIRT is an effective treatment option for patients with metastatic liver disease in a salvage setting with acceptable toxicity. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cancer risk primary sclerosing cholangitis epidemiology prevention surveillance strategies primary sclerosing cholangitis psc rare cholestatic liver disease characterized progressive fibroinflammatory destruction intra extrahepatic biliary ducts features disease course variable patients psc concurrent inflammatory bowel disease eventually develop liver cirrhosis end stage liver disease liver transplantation representing potentially curative option importantly psc associated significantly increased risk malignancy compared general population mainly cholangiocarcinoma gallbladder carcinoma hepatocellular carcinoma colorectal cancer nearly 50 deaths patients psc due cancer therefore robust surveillance strategies needed though uncertainty remains regarding best review discuss epidemiology prevention surveillance cancers patients psc evidence limited present pragmatic approaches based currently available data expert opinion pubmed","probabilities":0.9799733,"Title":"Cancer risk in primary sclerosing cholangitis: Epidemiology, prevention, and surveillance strategies","Abstract":"Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra- and/or extrahepatic biliary ducts. While its features and disease course can be variable, most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly, PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion.","Source":"PubMed","category":"HUMAN","training_data":"Cancer risk in primary sclerosing cholangitis: Epidemiology, prevention, and surveillance strategies Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra- and/or extrahepatic biliary ducts. While its features and disease course can be variable, most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly, PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion. PubMed","prediction_labels":"HUMAN"},{"cleaned":"poor prognosis advanced cholangiocarcinoma real world data tertiary referral center background incidence cholangiocarcinoma cca western countries rising palliative setting chemotherapy established treatment evidence treatments including locoregional therapy low however individual treatments offered real world setting aim study document offered treatments analyze survival patients unresectable cca treated tertiary referral center patients methods data 220 consecutive patients cca treated german university cancer center january 1 2008 december 31 2012 105 patients unresectable survival curves calculated according kaplan meier method log rank test applied survival analysis results palliative treatment beneficial patients unresectable cca compared best supportive care bsc alone median os bsc 10 weeks bsc vs transarterial chemoembolization tace p 0 017 hr 0 36 bsc vs tace chemotherapy p 0 001 hr 0 24 bsc vs chemotherapy p 0 001 hr 0 31 combination tace chemotherapy prolonged overall survival compared tace alone 105 vs 43 weeks p 0 045 conclusion prognosis advanced stage cca still poor however multimodal treatment palliative patients significantly prolong survival stn","probabilities":0.9799733,"Title":"Poor Prognosis Of Advanced Cholangiocarcinoma: Real-World Data From A Tertiary Referral Center","Abstract":"Background: Incidence of cholangiocarcinoma (CCA) in western countries is rising. In the palliative setting, chemotherapy is the only established treatment. The evidence for other treatments including locoregional therapy is low. However, such individual treatments are offered in a real-world setting. The aim of this study is to document the offered treatments and to analyze the survival of patients with unresectable CCA treated at a tertiary referral center. \r\n\r\n Patients and methods: Data from 220 consecutive patients with CCA treated at a German university cancer center from January 1, 2008, until December 31, 2012. Of those, 105 patients were unresectable. Survival curves were calculated according to the Kaplan-Meier method; log-rank test was applied for survival analysis. \r\n\r\n Results: Any palliative treatment was beneficial for patients with unresectable CCA when compared to best supportive care (BSC) alone; median OS with BSC was 10 weeks (BSC vs. transarterial chemoembolization [TACE] p = 0.017, HR 0.36; BSC vs. TACE/chemotherapy p < 0.001, HR 0.24; BSC vs. chemotherapy p < 0.001, HR 0.31). Combination of TACE and chemotherapy prolonged overall survival as compared to TACE alone (105 vs. 43 weeks, p = 0.045). \r\n\r\n Conclusion: Prognosis in advanced stage CCA is still very poor. However, multimodal treatment in palliative patients significantly prolong survival.","Source":"STN","category":"HUMAN","training_data":"Poor Prognosis Of Advanced Cholangiocarcinoma: Real-World Data From A Tertiary Referral Center Background: Incidence of cholangiocarcinoma (CCA) in western countries is rising. In the palliative setting, chemotherapy is the only established treatment. The evidence for other treatments including locoregional therapy is low. However, such individual treatments are offered in a real-world setting. The aim of this study is to document the offered treatments and to analyze the survival of patients with unresectable CCA treated at a tertiary referral center. \r\n\r\n Patients and methods: Data from 220 consecutive patients with CCA treated at a German university cancer center from January 1, 2008, until December 31, 2012. Of those, 105 patients were unresectable. Survival curves were calculated according to the Kaplan-Meier method; log-rank test was applied for survival analysis. \r\n\r\n Results: Any palliative treatment was beneficial for patients with unresectable CCA when compared to best supportive care (BSC) alone; median OS with BSC was 10 weeks (BSC vs. transarterial chemoembolization [TACE] p = 0.017, HR 0.36; BSC vs. TACE/chemotherapy p < 0.001, HR 0.24; BSC vs. chemotherapy p < 0.001, HR 0.31). Combination of TACE and chemotherapy prolonged overall survival as compared to TACE alone (105 vs. 43 weeks, p = 0.045). \r\n\r\n Conclusion: Prognosis in advanced stage CCA is still very poor. However, multimodal treatment in palliative patients significantly prolong survival. STN","prediction_labels":"HUMAN"},{"cleaned":"clinical manifestation prognosis combined hepatocellularcholangiocarcinoma clinical manifestation prognosis combined hepatocellularcholangiocarcinoma primasari deaningtyas1 andri sanityoso s2 chyntia o jasirwan2 1internal medicine resident faculty medicine university indonesia 2staff hepatology division faculty medicine university indonesia introduction combined hepatocellular cholangiocarcinoma chc rare hepatobiliary neoplasia incidence ranging 1 0 4 7 tumor poor prognosis hardly diagnose preoperatively 1this presentation chc related prognosis factor disease progression monitoring case ilustration 42 years old male came abdominal discomfort right hipocondrium quadrant since 3 months prior hospital visit insignificant weight loss usg showed hepatic mass absence history hematemesis melena diabetes jaundice overweight normal sclera mild abdominal pain diagnosed hepatitis b infection mild elevation alpha fetoprotein 69 67 mg dl abdominal ct scan revealed hypodense lesion 3 3 9 3 8 9 4 cm mesenterium lymphadenopathy abdominal anterior wall defect passed hepatectomy right hemicolectomy biopsy showed combined hepatocellular cholangiocarcinoma ileocolitis lymphadenopathy infiltration tenofovir administer patient two months surgery new lesion liver segmen 5 7 diameter 1 6 cm 2 8 cm discussion 1 3 5 year survival rates chc liver resection 73 9 41 4 36 4 tumor node metastasis system stage hazard ratio 1 27 p 0 003 radical liver resection hazard ratio 0 31 p 0 004 independent prognostic factors 2 3 4 line previous researchs patient shows progressive disease spite involvement lymphadenopathy small size tumor conclusion although rare occurrence chc still managed discovered early stage progressive character poor prognosis demand close monitoring improve survival google scholar","probabilities":0.9799733,"Title":"Clinical Manifestation And Prognosis Of Combined Hepatocellularcholangiocarcinoma","Abstract":"Clinical manifestation and prognosis of combined hepatocellularcholangiocarcinoma Primasari Deaningtyas1, Andri Sanityoso S2, Chyntia O Jasirwan2 1Internal Medicine Resident Faculty of Medicine University of Indonesia, 2Staff of Hepatology Division Faculty of Medicine University of Indonesia Introduction: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare hepatobiliary neoplasia with incidence ranging from 1.0 to 4.7%. This tumor has poor prognosis and hardly to diagnose preoperatively. 1This is a presentation CHC, related prognosis factor and disease progression monitoring. Case ilustration: A 42 years old male came with abdominal discomfort in right hipocondrium quadrant since 3 months prior to hospital visit. There was insignificant weight loss. His USG showed hepatic mass. There was absence history of hematemesis melena, diabetes, and jaundice. He is overweight with normal sclera, and mild abdominal pain. He diagnosed with hepatitis B infection and mild elevation of alpha fetoprotein (69.67 mg/dL. His abdominal CT scan revealed a hypodense lesion 3.3 9 3.8 9 4 cm with mesenterium lymphadenopathy and abdominal anterior wall defect. He passed hepatectomy and right hemicolectomy. His biopsy showed combined hepatocellular-cholangiocarcinoma, ileocolitis and no lymphadenopathy infiltration. Tenofovir was administer to the patient. Two months after surgery, there is new lesion in liver segmen 5 and 7 with diameter 1.6 cm and 2.8 cm. Discussion: The 1-, 3-, and 5-year survival rates of CHC after liver resection were 73.9, 41.4, and 36.4%. Tumor, node, metastasis system stage (hazard ratio 1.27, p = 0.003) and radical liver resection (hazard ratio 0.31, p = 0.004) were independent prognostic factors.2,3,4 In line with previous researchs, this patient shows progressive disease in spite of no involvement of lymphadenopathy and small size tumor. Conclusion: Although rare occurrence, CHC still can be managed if discovered in early stage. Its progressive character and poor prognosis demand close monitoring to improve its survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Clinical Manifestation And Prognosis Of Combined Hepatocellularcholangiocarcinoma Clinical manifestation and prognosis of combined hepatocellularcholangiocarcinoma Primasari Deaningtyas1, Andri Sanityoso S2, Chyntia O Jasirwan2 1Internal Medicine Resident Faculty of Medicine University of Indonesia, 2Staff of Hepatology Division Faculty of Medicine University of Indonesia Introduction: Combined hepatocellular-cholangiocarcinoma (CHC) is a rare hepatobiliary neoplasia with incidence ranging from 1.0 to 4.7%. This tumor has poor prognosis and hardly to diagnose preoperatively. 1This is a presentation CHC, related prognosis factor and disease progression monitoring. Case ilustration: A 42 years old male came with abdominal discomfort in right hipocondrium quadrant since 3 months prior to hospital visit. There was insignificant weight loss. His USG showed hepatic mass. There was absence history of hematemesis melena, diabetes, and jaundice. He is overweight with normal sclera, and mild abdominal pain. He diagnosed with hepatitis B infection and mild elevation of alpha fetoprotein (69.67 mg/dL. His abdominal CT scan revealed a hypodense lesion 3.3 9 3.8 9 4 cm with mesenterium lymphadenopathy and abdominal anterior wall defect. He passed hepatectomy and right hemicolectomy. His biopsy showed combined hepatocellular-cholangiocarcinoma, ileocolitis and no lymphadenopathy infiltration. Tenofovir was administer to the patient. Two months after surgery, there is new lesion in liver segmen 5 and 7 with diameter 1.6 cm and 2.8 cm. Discussion: The 1-, 3-, and 5-year survival rates of CHC after liver resection were 73.9, 41.4, and 36.4%. Tumor, node, metastasis system stage (hazard ratio 1.27, p = 0.003) and radical liver resection (hazard ratio 0.31, p = 0.004) were independent prognostic factors.2,3,4 In line with previous researchs, this patient shows progressive disease in spite of no involvement of lymphadenopathy and small size tumor. Conclusion: Although rare occurrence, CHC still can be managed if discovered in early stage. Its progressive character and poor prognosis demand close monitoring to improve its survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"shikonin induces apoptosis g0 g1 phase arrest gallbladder cancer cells via jnk signaling pathway shikonin natural product isolated roots lithospermum erythrorhizon considered antitumor effects gallbladder cancer gbc prevalent biliary tract malignancy curative therapeutic stragegies poor prognosis present study detected effects shikonin gbc cells well underlying molecular mechanisms results demonstrated gbc cell proliferation inhibited shikonin determined mtt colony formation assays flow cytometry results demonstrated shikonin treatment enhanced apoptosis promoted g0 g1 phase arrest gbc cells western blot assay showed shikonin induced mitochondrial dependent apoptosis via jnk signaling pathway moreover shikonin suppressed tumor growth mice bearing gbc derived xenografts dose dependent manner without side effects results revealed shikonin exhibits anticancer effects gbc cells inducing apoptosis regulating cell cycle taken together shikonin may novel safe chemotherapeutic agent treatment gbc stn","probabilities":0.9467213,"Title":"Shikonin Induces Apoptosis And G0/G1 Phase Arrest Of Gallbladder Cancer Cells Via The Jnk Signaling Pathway","Abstract":"Shikonin, a natural product isolated from the roots of Lithospermum erythrorhizon, is considered to have antitumor effects. Gallbladder cancer (GBC) is a prevalent biliary tract malignancy with few curative therapeutic stragegies and poor prognosis. In the present study, we detected the effects of shikonin on GBC cells as well as the underlying molecular mechanisms. The results demonstrated that GBC cell proliferation was inhibited by shikonin as determined by MTT and colony formation assays. Flow cytometry results demonstrated that shikonin treatment enhanced apoptosis and promoted G0/G1 phase arrest in the GBC cells. Western blot assay showed that shikonin induced mitochondrial-dependent apoptosis via the JNK signaling pathway. Moreover, shikonin suppressed tumor growth in mice bearing GBC-derived xenografts in a dose‑dependent manner without side-effects. These results revealed that shikonin exhibits anticancer effects on GBC cells by inducing apoptosis and regulating the cell cycle. Taken together, shikonin may be a novel and safe chemotherapeutic agent for the treatment of GBC.","Source":"STN","category":"ANIMAL","training_data":"Shikonin Induces Apoptosis And G0/G1 Phase Arrest Of Gallbladder Cancer Cells Via The Jnk Signaling Pathway Shikonin, a natural product isolated from the roots of Lithospermum erythrorhizon, is considered to have antitumor effects. Gallbladder cancer (GBC) is a prevalent biliary tract malignancy with few curative therapeutic stragegies and poor prognosis. In the present study, we detected the effects of shikonin on GBC cells as well as the underlying molecular mechanisms. The results demonstrated that GBC cell proliferation was inhibited by shikonin as determined by MTT and colony formation assays. Flow cytometry results demonstrated that shikonin treatment enhanced apoptosis and promoted G0/G1 phase arrest in the GBC cells. Western blot assay showed that shikonin induced mitochondrial-dependent apoptosis via the JNK signaling pathway. Moreover, shikonin suppressed tumor growth in mice bearing GBC-derived xenografts in a dose‑dependent manner without side-effects. These results revealed that shikonin exhibits anticancer effects on GBC cells by inducing apoptosis and regulating the cell cycle. Taken together, shikonin may be a novel and safe chemotherapeutic agent for the treatment of GBC. STN","prediction_labels":"ANIMAL"},{"cleaned":"association physical activity type intensity digestive system cancer risk importance accumulating evidence indicates common carcinogenic pathways may underlie digestive system cancers physical activity may influence pathways yet knowledge previous study evaluated role physical activity overall digestive system cancer risk objective examine association physical activity digestive system cancer risk accounting amount type aerobic vs resistance intensity physical activity design setting participants prospective cohort study followed 43 479 men health professionals follow study 1986 2012 enrollment eligible participants 40 years older free cancer reported physical activity follow rates exceeded 90 2 year cycle exposures amount total physical activity expressed metabolic equivalent task met hours week main outcomes measures incident cancer digestive system encompassing digestive tract mouth throat esophagus stomach small intestine colorectum digestive accessory organs pancreas gallbladder liver results 686 924 person years documented 1370 incident digestive system cancers higher levels physical activity associated lower digestive system cancer risk hazard ratio hr 0 74 63 0 vs 8 9 met hours week 95 ci 0 59 0 93 p value trend 003 inverse association evident digestive tract cancers hr 0 66 63 0 vs 8 9 met hours week 95 ci 0 51 0 87 digestive accessary organ cancers aerobic exercise particularly beneficial digestive system cancers optimal benefit observed approximately 30 met hours week hr 0 68 95 ci 0 56 0 83 p value nonlinearity 02 moreover long level met hour score achieved aerobic exercise magnitude risk reduction similar regardless intensity aerobic exercise conclusions relevance physical activity indicated met hours week inversely associated risk digestive system cancers particularly digestive tract cancers men optimal benefit observed aerobic exercise intensity equivalent energy expenditure approximately 10 hours week walking average pace future studies warranted confirm findings translate clinical public health recommendation pubmed","probabilities":0.9799733,"Title":"Association of Physical Activity by Type and Intensity With Digestive System Cancer Risk","Abstract":"IMPORTANCE: Accumulating evidence indicates that common carcinogenic pathways may underlie digestive system cancers. Physical activity may influence these pathways. Yet, to our knowledge, no previous study has evaluated the role of physical activity in overall digestive system cancer risk. OBJECTIVE: To examine the association between physical activity and digestive system cancer risk, accounting for amount, type (aerobic vs resistance), and intensity of physical activity. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study followed 43 479 men from the Health Professionals Follow-up Study from 1986 to 2012. At enrollment, the eligible participants were 40 years or older, were free of cancer, and reported physical activity. Follow-up rates exceeded 90% in each 2-year cycle. EXPOSURES: The amount of total physical activity expressed in metabolic equivalent of task (MET)-hours/week. MAIN OUTCOMES AND MEASURES: Incident cancer of the digestive system encompassing the digestive tract (mouth, throat, esophagus, stomach, small intestine, and colorectum) and digestive accessory organs (pancreas, gallbladder, and liver). RESULTS: Over 686 924 person-years, we documented 1370 incident digestive system cancers. Higher levels of physical activity were associated with lower digestive system cancer risk (hazard ratio [HR], 0.74 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.59-0.93; P value for trend = .003). The inverse association was more evident with digestive tract cancers (HR, 0.66 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.51-0.87) than with digestive accessary organ cancers. Aerobic exercise was particularly beneficial against digestive system cancers, with the optimal benefit observed at approximately 30 MET-hours/week (HR, 0.68; 95% CI, 0.56-0.83; P value for nonlinearity = .02). Moreover, as long as the same level of MET-hour score was achieved from aerobic exercise, the magnitude of risk reduction was similar regardless of intensity of aerobic exercise. CONCLUSIONS AND RELEVANCE: Physical activity, as indicated by MET-hours/week, was inversely associated with the risk of digestive system cancers, particularly digestive tract cancers, in men. The optimal benefit was observed through aerobic exercise of any intensity at the equivalent of energy expenditure of approximately 10 hours/week of walking at average pace. Future studies are warranted to confirm our findings and to translate them into clinical and public health recommendation.","Source":"PubMed","category":"HUMAN","training_data":"Association of Physical Activity by Type and Intensity With Digestive System Cancer Risk IMPORTANCE: Accumulating evidence indicates that common carcinogenic pathways may underlie digestive system cancers. Physical activity may influence these pathways. Yet, to our knowledge, no previous study has evaluated the role of physical activity in overall digestive system cancer risk. OBJECTIVE: To examine the association between physical activity and digestive system cancer risk, accounting for amount, type (aerobic vs resistance), and intensity of physical activity. DESIGN, SETTING, AND PARTICIPANTS: A prospective cohort study followed 43 479 men from the Health Professionals Follow-up Study from 1986 to 2012. At enrollment, the eligible participants were 40 years or older, were free of cancer, and reported physical activity. Follow-up rates exceeded 90% in each 2-year cycle. EXPOSURES: The amount of total physical activity expressed in metabolic equivalent of task (MET)-hours/week. MAIN OUTCOMES AND MEASURES: Incident cancer of the digestive system encompassing the digestive tract (mouth, throat, esophagus, stomach, small intestine, and colorectum) and digestive accessory organs (pancreas, gallbladder, and liver). RESULTS: Over 686 924 person-years, we documented 1370 incident digestive system cancers. Higher levels of physical activity were associated with lower digestive system cancer risk (hazard ratio [HR], 0.74 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.59-0.93; P value for trend = .003). The inverse association was more evident with digestive tract cancers (HR, 0.66 for ≥63.0 vs ≤8.9 MET-hours/week; 95% CI, 0.51-0.87) than with digestive accessary organ cancers. Aerobic exercise was particularly beneficial against digestive system cancers, with the optimal benefit observed at approximately 30 MET-hours/week (HR, 0.68; 95% CI, 0.56-0.83; P value for nonlinearity = .02). Moreover, as long as the same level of MET-hour score was achieved from aerobic exercise, the magnitude of risk reduction was similar regardless of intensity of aerobic exercise. CONCLUSIONS AND RELEVANCE: Physical activity, as indicated by MET-hours/week, was inversely associated with the risk of digestive system cancers, particularly digestive tract cancers, in men. The optimal benefit was observed through aerobic exercise of any intensity at the equivalent of energy expenditure of approximately 10 hours/week of walking at average pace. Future studies are warranted to confirm our findings and to translate them into clinical and public health recommendation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clues predict incidental gallbladder cancer background consequences incidental gallbladder cancer igbc following cholecystectomy may include repeat operation depending stage worse survival bile spillage occurred avoidable igbc suspected preoperatively methods retrospective single institution review done ultrasound images cases controls blindly reviewed radiologist chi square student tests well logistic regression kaplan meier analyses used p 0 01 considered significant results among 5796 cholecystectomies performed 2000 2013 26 0 45 igbc cases patients older 75 61 versus 52 27 years laparoscopic open conversions 23 1 versus 3 9 underwent imaging tests larger common bile duct diameter 7 13 versus 5 04 mm higher alkaline phosphatase ultrasound imaging showed gallbladder wall thickening gbwt without pericholecystic fluid pccf focal versus diffuse gbwt associated significantly igbc 73 9 versus 47 4 multivariable logistic regression analysis gbwt without pccf age strongest predictors igbc consequences igbc depended significantly intraoperative bile spillage nearly patients developing carcinomatosis significantly worse survival conclusions besides age gbwt dilated common bile duct elevated alkaline phosphatase number preoperative imaging modalities presence gbwt without pccf useful predictors igbc bile spillage causes poor survival patients igbc pubmed","probabilities":0.9799733,"Title":"Clues to predict incidental gallbladder cancer","Abstract":"BACKGROUND: Consequences of incidental gallbladder cancer (iGBC) following cholecystectomy may include repeat operation (depending on T stage) and worse survival (if bile spillage occurred), both avoidable if iGBC were suspected preoperatively. METHODS: A retrospective single-institution review was done. Ultrasound images for cases and controls were blindly reviewed by a radiologist. Chi-square and Student's t tests, as well as logistic regression and Kaplan-Meier analyses were used. A P ≤ 0.01 was considered significant. RESULTS: Among 5796 cholecystectomies performed 2000-2013, 26 (0.45%) were iGBC cases. These patients were older (75.61 versus 52.27 years), had more laparoscopic-to-open conversions (23.1% versus 3.9%), underwent more imaging tests, had larger common bile duct diameter (7.13 versus 5.04 mm) and higher alkaline phosphatase. Ultrasound imaging showed that gallbladder wall thickening (GBWT) without pericholecystic fluid (PCCF), but not focal-versus-diffuse GBWT, was associated significantly with iGBC (73.9% versus 47.4%). On multivariable logistic regression analysis, GBWT without PCCF, and age were the strongest predictors of iGBC. The consequences iGBC depended significantly on intraoperative bile spillage, with nearly all such patients developing carcinomatosis and significantly worse survival. CONCLUSIONS: Besides age, GBWT, dilated common bile duct, and elevated alkaline phosphatase, number of preoperative imaging modalities and the presence of GBWT without PCCF are useful predictors of iGBC. Bile spillage causes poor survival in patients with iGBC.","Source":"PubMed","category":"HUMAN","training_data":"Clues to predict incidental gallbladder cancer BACKGROUND: Consequences of incidental gallbladder cancer (iGBC) following cholecystectomy may include repeat operation (depending on T stage) and worse survival (if bile spillage occurred), both avoidable if iGBC were suspected preoperatively. METHODS: A retrospective single-institution review was done. Ultrasound images for cases and controls were blindly reviewed by a radiologist. Chi-square and Student's t tests, as well as logistic regression and Kaplan-Meier analyses were used. A P ≤ 0.01 was considered significant. RESULTS: Among 5796 cholecystectomies performed 2000-2013, 26 (0.45%) were iGBC cases. These patients were older (75.61 versus 52.27 years), had more laparoscopic-to-open conversions (23.1% versus 3.9%), underwent more imaging tests, had larger common bile duct diameter (7.13 versus 5.04 mm) and higher alkaline phosphatase. Ultrasound imaging showed that gallbladder wall thickening (GBWT) without pericholecystic fluid (PCCF), but not focal-versus-diffuse GBWT, was associated significantly with iGBC (73.9% versus 47.4%). On multivariable logistic regression analysis, GBWT without PCCF, and age were the strongest predictors of iGBC. The consequences iGBC depended significantly on intraoperative bile spillage, with nearly all such patients developing carcinomatosis and significantly worse survival. CONCLUSIONS: Besides age, GBWT, dilated common bile duct, and elevated alkaline phosphatase, number of preoperative imaging modalities and the presence of GBWT without PCCF are useful predictors of iGBC. Bile spillage causes poor survival in patients with iGBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact stroma loxl2 overexpression prognosis intrahepatic cholangiocarcinoma background intrahepatic cholangiocarcinoma icc associated poor prognosis related early recurrence especially remnant liver surgery icc exhibits dense desmoplastic stroma plays pivotal role icc aggressiveness thus analyzing gene deregulation stroma icc may help identify new prognosis biomarkers promising therapeutic targets aim study evaluate clinical relevance matrix remodeling enzyme lysyl oxidase like 2 loxl2 expression icc material methods loxl2 messenger rna levels evaluated microdissected tumoral stroma ts nontumoral fibrous tissue gene expression profiling testing set n 10 obtained gene expression omnibus database quantitative real time polymerase chain reaction validating set n 6 loxl2 protein levels evaluated immunohistochemistry tissue microarray containing 80 independent patients relationship loxl2 expression survival assessed univariate multivariate analyses results loxl2 messenger rna levels increased ts testing validating sets p 0 01 results confirmed protein level significantly higher loxl2 immunostaining ts p 0 01 univariate analysis revealed loxl2 expression correlated poor overall survival disease free survival p 0 01 importantly high expression loxl2 independent prognostic factor worst overall survival hazard ratio 5 29 confidence interval ci 95 1 71 16 3 p 0 01 disease free survival hazard ratio 5 55 ci 95 2 14 14 37 p 0 01 conclusions study provides additional arguments role extracellular matrix remodeling icc aggressiveness identifies loxl2 new prognostic marker promising therapeutic target icc pubmed","probabilities":0.7966102,"Title":"Impact of stroma LOXL2 overexpression on the prognosis of intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis related to early recurrence especially in the remnant liver after surgery. ICC exhibits a dense desmoplastic stroma which plays a pivotal role in ICC aggressiveness. Thus, analyzing gene deregulation in the stroma of ICC may help to identify new prognosis biomarkers and promising therapeutic targets. The aim of this study was to evaluate the clinical relevance of the matrix-remodeling enzyme lysyl oxidase-like 2 (LOXL2) expression in ICC. MATERIAL AND METHODS: LOXL2 messenger RNA levels were evaluated in microdissected tumoral stroma (TS) and in nontumoral fibrous tissue by gene expression profiling (testing set, n = 10) obtained from gene expression omnibus database and by quantitative real time polymerase chain reaction (validating set, n = 6). LOXL2 protein levels were evaluated by immunohistochemistry on a tissue microarray containing 80 independent patients. The relationship between LOXL2 expression and survival was assessed by univariate and multivariate analyses. RESULTS: LOXL2 messenger RNA levels were increased in TS, both in the testing and the validating sets (P < 0.01). These results were confirmed at a protein level, with a significantly higher LOXL2 immunostaining in TS (P < 0.01). Univariate analysis revealed that LOXL2 expression was correlated with a poor overall survival and disease-free survival (P < 0.01). Importantly, high expression of LOXL2 was an independent prognostic factor of worst overall survival (hazard ratio = 5.29, confidence interval [CI] 95% = 1.71-16.3, P < 0.01) and disease-free survival (hazard ratio = 5.55, CI 95% = 2.14-14.37, P < 0.01). CONCLUSIONS: Our study provides additional arguments for a role of extracellular matrix remodeling in ICC aggressiveness and identifies LOXL2 as a new prognostic marker and a promising therapeutic target in ICC.","Source":"PubMed","category":"HUMAN","training_data":"Impact of stroma LOXL2 overexpression on the prognosis of intrahepatic cholangiocarcinoma BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis related to early recurrence especially in the remnant liver after surgery. ICC exhibits a dense desmoplastic stroma which plays a pivotal role in ICC aggressiveness. Thus, analyzing gene deregulation in the stroma of ICC may help to identify new prognosis biomarkers and promising therapeutic targets. The aim of this study was to evaluate the clinical relevance of the matrix-remodeling enzyme lysyl oxidase-like 2 (LOXL2) expression in ICC. MATERIAL AND METHODS: LOXL2 messenger RNA levels were evaluated in microdissected tumoral stroma (TS) and in nontumoral fibrous tissue by gene expression profiling (testing set, n = 10) obtained from gene expression omnibus database and by quantitative real time polymerase chain reaction (validating set, n = 6). LOXL2 protein levels were evaluated by immunohistochemistry on a tissue microarray containing 80 independent patients. The relationship between LOXL2 expression and survival was assessed by univariate and multivariate analyses. RESULTS: LOXL2 messenger RNA levels were increased in TS, both in the testing and the validating sets (P < 0.01). These results were confirmed at a protein level, with a significantly higher LOXL2 immunostaining in TS (P < 0.01). Univariate analysis revealed that LOXL2 expression was correlated with a poor overall survival and disease-free survival (P < 0.01). Importantly, high expression of LOXL2 was an independent prognostic factor of worst overall survival (hazard ratio = 5.29, confidence interval [CI] 95% = 1.71-16.3, P < 0.01) and disease-free survival (hazard ratio = 5.55, CI 95% = 2.14-14.37, P < 0.01). CONCLUSIONS: Our study provides additional arguments for a role of extracellular matrix remodeling in ICC aggressiveness and identifies LOXL2 as a new prognostic marker and a promising therapeutic target in ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"perineural invasion extrahepatic cholangiocarcinoma prognostic impact treatment strategies background significance perineural invasion extrahepatic cholangiocarcinoma fully elucidated study aims determine prognostic impact optimal treatment strategy perineural invasion patients extrahepatic cholangiocarcinoma methods medical records 133 patients extrahepatic cholangiocarcinoma underwent curative resection reviewed retrospectively ninety eight patients perineural invasion 35 patients univariate multivariate survival analyses performed clarify prognostic impact optimal treatment strategy perineural invasion results tumor differentiation p 0 024 independently associated perineural invasion multivariate logistic regression model multivariate survival analysis revealed perineural invasion p 0 002 resection margin status p 0 016 international union cancer uicc pt factor p 0 015 independent prognostic factors overall survival overall 5 year survival rates patients without perineural invasion 28 74 respectively among 98 patients perineural invasion use adjuvant chemotherapy p 0 003 lymph node status p 0 015 resection margin status p 0 008 uicc pt factor p 0 016 independently associated overall survival multivariate analysis overall 5 year survival rates patients perineural invasion receive adjuvant chemotherapy 33 21 respectively p 0 023 conclusions perineural invasion potent prognostic factor extrahepatic cholangiocarcinoma adjuvant chemotherapy may improve overall survival patients perineural invasion pubmed","probabilities":0.9799733,"Title":"Perineural invasion in extrahepatic cholangiocarcinoma: prognostic impact and treatment strategies","Abstract":"BACKGROUND: The significance of perineural invasion in extrahepatic cholangiocarcinoma has not been fully elucidated. This study aims to determine the prognostic impact of and optimal treatment strategy for perineural invasion in patients with extrahepatic cholangiocarcinoma. METHODS: Medical records of 133 patients with extrahepatic cholangiocarcinoma who underwent curative resection were reviewed retrospectively. Ninety-eight patients had perineural invasion and 35 patients did not. Univariate and multivariate survival analyses were performed to clarify the prognostic impact of and optimal treatment strategy for perineural invasion. RESULTS: Only tumor differentiation (P=0.024) was independently associated with perineural invasion in the multivariate logistic regression model. Multivariate survival analysis revealed that perineural invasion (P=0.002), resection margin status(P=0.016), and International Union Against Cancer (UICC) pT factor (P=0.015) were independent prognostic factors of overall survival. Overall 5-year survival rates for patients with and without perineural invasion were 28 and 74 %, respectively. Among 98 patients with perineural invasion, the use of adjuvant chemotherapy (P=0.003), lymph node status (P=0.015), resection margin status (P=0.008), and UICC pT factor (P=0.016) were independently associated with overall survival by multivariate analysis. Overall 5-year survival rates for patients with perineural invasion who did and did not receive adjuvant chemotherapy were 33 and 21 %, respectively (P=0.023). CONCLUSIONS: Perineural invasion is a potent prognostic factor in extrahepatic cholangiocarcinoma. Adjuvant chemotherapy may improve the overall survival of patients with perineural invasion.","Source":"PubMed","category":"HUMAN","training_data":"Perineural invasion in extrahepatic cholangiocarcinoma: prognostic impact and treatment strategies BACKGROUND: The significance of perineural invasion in extrahepatic cholangiocarcinoma has not been fully elucidated. This study aims to determine the prognostic impact of and optimal treatment strategy for perineural invasion in patients with extrahepatic cholangiocarcinoma. METHODS: Medical records of 133 patients with extrahepatic cholangiocarcinoma who underwent curative resection were reviewed retrospectively. Ninety-eight patients had perineural invasion and 35 patients did not. Univariate and multivariate survival analyses were performed to clarify the prognostic impact of and optimal treatment strategy for perineural invasion. RESULTS: Only tumor differentiation (P=0.024) was independently associated with perineural invasion in the multivariate logistic regression model. Multivariate survival analysis revealed that perineural invasion (P=0.002), resection margin status(P=0.016), and International Union Against Cancer (UICC) pT factor (P=0.015) were independent prognostic factors of overall survival. Overall 5-year survival rates for patients with and without perineural invasion were 28 and 74 %, respectively. Among 98 patients with perineural invasion, the use of adjuvant chemotherapy (P=0.003), lymph node status (P=0.015), resection margin status (P=0.008), and UICC pT factor (P=0.016) were independently associated with overall survival by multivariate analysis. Overall 5-year survival rates for patients with perineural invasion who did and did not receive adjuvant chemotherapy were 33 and 21 %, respectively (P=0.023). CONCLUSIONS: Perineural invasion is a potent prognostic factor in extrahepatic cholangiocarcinoma. Adjuvant chemotherapy may improve the overall survival of patients with perineural invasion. PubMed","prediction_labels":"HUMAN"},{"cleaned":"threonine tyrosine kinase may serve prognostic biomarker gallbladder cancer aim detect expression threonine tyrosine kinase ttk gallbladder cancer gbc specimens analyze associations ttk expression clinicopathological parameters clinical prognosis methods total 68 patients gbc underwent surgical resection enrolled study expression ttk gbc tissues detected immunohistochemistry assessment ttk expression conducted using h scoring system h score calculated multiplication overall staining intensity percentage positive cells expression ttk cytoplasm nucleus scored separately achieve respective h score values correlations ttk expression clinicopathological parameters clinical prognosis analyzed using chi square test kaplan meier method cox regression results nucleus cytoplasm expression ttk tumor tissues significantly lower normal tissues p 0 001 p 0 026 respectively using median h score cutoff value discovered gbc patients higher levels ttk expression nucleus cytoplasm favorable overall survival p 0 001 still statistically meaningful cox regression analysis investigation indicated close negative correlations ttk expression tumor differentiation p 0 041 ca 19 9 levels p 0 016 stage p 0 001 nodal involvement p 0 001 distant metastasis p 0 024 tnm stage p 0 001 conclusion expression ttk gbc lower normal tissues higher levels ttk expression gbc concomitant longer overall survival ttk favorable prognostic biomarker patients gbc pubmed","probabilities":0.88235295,"Title":"Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer","Abstract":"AIM: To detect the expression of threonine and tyrosine kinase (TTK) in gallbladder cancer (GBC) specimens and analyze the associations between TTK expression and clinicopathological parameters and clinical prognosis. METHODS: A total of 68 patients with GBC who underwent surgical resection were enrolled in this study. The expression of TTK in GBC tissues was detected by immunohistochemistry. The assessment of TTK expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of TTK in the cytoplasm and nucleus was scored separately to achieve respective H-score values. The correlations between TTK expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. RESULTS: In both the nucleus and cytoplasm, the expression of TTK in tumor tissues was significantly lower than that in normal tissues (P < 0.001 and P = 0.026, respectively). Using the median H-score as the cutoff value, it was discovered that, GBC patients with higher levels of TTK expression in the nucleus, but not the cytoplasm, had favorable overall survival (P < 0.001), and it was still statistically meaningful in Cox regression analysis. Further investigation indicated that there were close negative correlations between TTK expression and tumor differentiation (P = 0.041), CA 19-9 levels (P = 0.016), T stage (P < 0.001), nodal involvement (P < 0.001), distant metastasis (P = 0.024) and TNM stage (P < 0.001). CONCLUSION: The expression of TTK in GBC is lower than that in normal tissues. Higher levels of TTK expression in GBC are concomitant with longer overall survival. TTK is a favorable prognostic biomarker for patients with GBC.","Source":"PubMed","category":"HUMAN","training_data":"Threonine and tyrosine kinase may serve as a prognostic biomarker for gallbladder cancer AIM: To detect the expression of threonine and tyrosine kinase (TTK) in gallbladder cancer (GBC) specimens and analyze the associations between TTK expression and clinicopathological parameters and clinical prognosis. METHODS: A total of 68 patients with GBC who underwent surgical resection were enrolled in this study. The expression of TTK in GBC tissues was detected by immunohistochemistry. The assessment of TTK expression was conducted using the H-scoring system. H-score was calculated by the multiplication of the overall staining intensity with the percentage of positive cells. The expression of TTK in the cytoplasm and nucleus was scored separately to achieve respective H-score values. The correlations between TTK expression and clinicopathological parameters and clinical prognosis were analyzed using Chi-square test, Kaplan-Meier method and Cox regression. RESULTS: In both the nucleus and cytoplasm, the expression of TTK in tumor tissues was significantly lower than that in normal tissues (P < 0.001 and P = 0.026, respectively). Using the median H-score as the cutoff value, it was discovered that, GBC patients with higher levels of TTK expression in the nucleus, but not the cytoplasm, had favorable overall survival (P < 0.001), and it was still statistically meaningful in Cox regression analysis. Further investigation indicated that there were close negative correlations between TTK expression and tumor differentiation (P = 0.041), CA 19-9 levels (P = 0.016), T stage (P < 0.001), nodal involvement (P < 0.001), distant metastasis (P = 0.024) and TNM stage (P < 0.001). CONCLUSION: The expression of TTK in GBC is lower than that in normal tissues. Higher levels of TTK expression in GBC are concomitant with longer overall survival. TTK is a favorable prognostic biomarker for patients with GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"underuse curative surgery early stage upper gastrointestinal cancers united states background surgery cornerstone potentially curative therapy upper gastrointestinal cancer analyzed patterns treatment regarding use surgery early stage upper gastrointestinal cancer united states methods surveillance epidemiology end research database used identify patients cancer esophagus stomach pancreas liver gallbladder biliary tract duodenum 2004 2007 patients potentially resectable stage ii disease selected primary outcome measure use curative intent surgery secondary outcomes predictors surgery results identified 29 249 patients median age 69 years 54 patients underwent cancer directed surgical resection ranging 28 liver cancer 89 gallbladder cancer remaining patients underwent either local excision 8 surgery 38 among surgery group patients 79 documented recommended resection independent variables multivariate analysis predictive nonoperative approach included black race age older 75 years tumor size greater 5 cm high poverty level p 0 001 patients undergo surgery worse median overall survival 3 years patients undergoing surgery 11 months versus 36 months 14 versus 43 respectively p 0 001 conclusions almost one half patients early stage upper gastrointestinal cancer receive potentially curative surgery adverse effect overall survival combination demographic tumor socioeconomic factors predictive lack surgical resection pubmed","probabilities":0.9799733,"Title":"Underuse of curative surgery for early stage upper gastrointestinal cancers in the United States","Abstract":"BACKGROUND: Surgery is the cornerstone of potentially curative therapy for upper gastrointestinal cancer. We analyzed the patterns of treatment regarding the use of surgery for early-stage upper gastrointestinal cancer in the United States. METHODS: The Surveillance, Epidemiology, and End Research database was used to identify patients with cancer of the esophagus, stomach, pancreas, liver, gallbladder, biliary tract, or duodenum (2004-2007). Only patients with potentially resectable stage I and II disease were selected. The primary outcome measure was the use of curative intent surgery. The secondary outcomes were the predictors of surgery. RESULTS: We identified 29,249 patients with a median age of 69 years. Only 54% of the patients underwent cancer-directed surgical resection, ranging from 28% for liver cancer to 89% for gallbladder cancer. The remaining patients underwent either local excision (8%) or no surgery (38%). Among the no surgery group, most patients (79%) were documented as \"not being recommended for resection.\" The independent variables on multivariate analysis predictive of a nonoperative approach included black race, age older than 75 years, tumor size greater than 5 cm, and high poverty level (P < 0.001). Patients who did not undergo surgery had worse median and overall survival at 3 years than patients undergoing surgery (11 months versus 36 months and 14% versus 43%, respectively; P < 0.001). CONCLUSIONS: Almost one half of patients with early-stage upper gastrointestinal cancer did not receive potentially curative surgery, with an adverse effect on overall survival. A combination of demographic, tumor, and socioeconomic factors were predictive of a lack of surgical resection.","Source":"PubMed","category":"HUMAN","training_data":"Underuse of curative surgery for early stage upper gastrointestinal cancers in the United States BACKGROUND: Surgery is the cornerstone of potentially curative therapy for upper gastrointestinal cancer. We analyzed the patterns of treatment regarding the use of surgery for early-stage upper gastrointestinal cancer in the United States. METHODS: The Surveillance, Epidemiology, and End Research database was used to identify patients with cancer of the esophagus, stomach, pancreas, liver, gallbladder, biliary tract, or duodenum (2004-2007). Only patients with potentially resectable stage I and II disease were selected. The primary outcome measure was the use of curative intent surgery. The secondary outcomes were the predictors of surgery. RESULTS: We identified 29,249 patients with a median age of 69 years. Only 54% of the patients underwent cancer-directed surgical resection, ranging from 28% for liver cancer to 89% for gallbladder cancer. The remaining patients underwent either local excision (8%) or no surgery (38%). Among the no surgery group, most patients (79%) were documented as \"not being recommended for resection.\" The independent variables on multivariate analysis predictive of a nonoperative approach included black race, age older than 75 years, tumor size greater than 5 cm, and high poverty level (P < 0.001). Patients who did not undergo surgery had worse median and overall survival at 3 years than patients undergoing surgery (11 months versus 36 months and 14% versus 43%, respectively; P < 0.001). CONCLUSIONS: Almost one half of patients with early-stage upper gastrointestinal cancer did not receive potentially curative surgery, with an adverse effect on overall survival. A combination of demographic, tumor, and socioeconomic factors were predictive of a lack of surgical resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comprehensive molecular profiling intrahepatic extrahepatic cholangiocarcinomas potential targets intervention purpose various genetic driver aberrations identified among distinct anatomic clinical subtypes intrahepatic extrahepatic cholangiocarcinoma molecular alterations may prognostic biomarkers predictive drug response experimental design tumor samples patients cholangiocarcinoma consented prospectively analyzed using msk impact platform targeted next generation sequencing assay analyzes exons selected introns 410 cancer associated genes fisher exact tests performed identify associations clinical characteristics genetic alterations results total 195 patients studied 78 intrahepatic 22 extrahepatic cholangiocarcinoma commonly altered genes intrahepatic cholangiocarcinoma idh1 30 arid1a 23 bap1 20 tp53 20 fgfr2 gene fusions 14 tendency toward mutual exclusivity seen multiple genes intrahepatic cholangiocarcinoma including tp53 idh1 idh1 kras tp53 bap1 idh1 fgfr2 alterations cdkn2a b erbb2 associated reduced survival time progression chemotherapy patients locally advanced metastatic disease genetic alterations potential therapeutic implications identified 47 patients leading biomarker directed therapy clinical trial enrollment 16 patients conclusions cholangiocarcinoma genetically diverse cancer alterations cdkn2a b erbb2 associated negative prognostic implications patients advanced disease somatic alterations therapeutic implications identified almost half patients prospective data provide contemporary benchmark guiding development targeted therapies molecularly profiled cholangiocarcinoma support use molecular profiling guide therapy selection patients advanced biliary cancers clin cancer res 24 17 4154 61 2018 aacr stn","probabilities":0.9799733,"Title":"Comprehensive Molecular Profiling Of Intrahepatic And Extrahepatic Cholangiocarcinomas: Potential Targets For Intervention","Abstract":"Purpose: Various genetic driver aberrations have been identified among distinct anatomic and clinical subtypes of intrahepatic and extrahepatic cholangiocarcinoma, and these molecular alterations may be prognostic biomarkers and/or predictive of drug response.Experimental Design: Tumor samples from patients with cholangiocarcinoma who consented prospectively were analyzed using the MSK-IMPACT platform, a targeted next-generation sequencing assay that analyzes all exons and selected introns of 410 cancer-associated genes. Fisher exact tests were performed to identify associations between clinical characteristics and genetic alterations.Results: A total of 195 patients were studied: 78% intrahepatic and 22% extrahepatic cholangiocarcinoma. The most commonly altered genes in intrahepatic cholangiocarcinoma were IDH1 (30%), ARID1A (23%), BAP1 (20%), TP53 (20%), and FGFR2 gene fusions (14%). A tendency toward mutual exclusivity was seen between multiple genes in intrahepatic cholangiocarcinoma including TP53:IDH1, IDH1:KRAS, TP53:BAP1, and IDH1:FGFR2 Alterations in CDKN2A/B and ERBB2 were associated with reduced survival and time to progression on chemotherapy in patients with locally advanced or metastatic disease. Genetic alterations with potential therapeutic implications were identified in 47% of patients, leading to biomarker-directed therapy or clinical trial enrollment in 16% of patients.Conclusions: Cholangiocarcinoma is a genetically diverse cancer. Alterations in CDKN2A/B and ERBB2 are associated with negative prognostic implications in patients with advanced disease. Somatic alterations with therapeutic implications were identified in almost half of patients. These prospective data provide a contemporary benchmark for guiding the development of targeted therapies in molecularly profiled cholangiocarcinoma, and support to the use of molecular profiling to guide therapy selection in patients with advanced biliary cancers. Clin Cancer Res; 24(17); 4154-61. ©2018 AACR.","Source":"STN","category":"HUMAN","training_data":"Comprehensive Molecular Profiling Of Intrahepatic And Extrahepatic Cholangiocarcinomas: Potential Targets For Intervention Purpose: Various genetic driver aberrations have been identified among distinct anatomic and clinical subtypes of intrahepatic and extrahepatic cholangiocarcinoma, and these molecular alterations may be prognostic biomarkers and/or predictive of drug response.Experimental Design: Tumor samples from patients with cholangiocarcinoma who consented prospectively were analyzed using the MSK-IMPACT platform, a targeted next-generation sequencing assay that analyzes all exons and selected introns of 410 cancer-associated genes. Fisher exact tests were performed to identify associations between clinical characteristics and genetic alterations.Results: A total of 195 patients were studied: 78% intrahepatic and 22% extrahepatic cholangiocarcinoma. The most commonly altered genes in intrahepatic cholangiocarcinoma were IDH1 (30%), ARID1A (23%), BAP1 (20%), TP53 (20%), and FGFR2 gene fusions (14%). A tendency toward mutual exclusivity was seen between multiple genes in intrahepatic cholangiocarcinoma including TP53:IDH1, IDH1:KRAS, TP53:BAP1, and IDH1:FGFR2 Alterations in CDKN2A/B and ERBB2 were associated with reduced survival and time to progression on chemotherapy in patients with locally advanced or metastatic disease. Genetic alterations with potential therapeutic implications were identified in 47% of patients, leading to biomarker-directed therapy or clinical trial enrollment in 16% of patients.Conclusions: Cholangiocarcinoma is a genetically diverse cancer. Alterations in CDKN2A/B and ERBB2 are associated with negative prognostic implications in patients with advanced disease. Somatic alterations with therapeutic implications were identified in almost half of patients. These prospective data provide a contemporary benchmark for guiding the development of targeted therapies in molecularly profiled cholangiocarcinoma, and support to the use of molecular profiling to guide therapy selection in patients with advanced biliary cancers. Clin Cancer Res; 24(17); 4154-61. ©2018 AACR. STN","prediction_labels":"HUMAN"},{"cleaned":"gene expression analysis predicting gemcitabine resistance human cholangiocarcinoma background gemcitabine promising drug cholangiocarcinoma treatment however kinetics metabolism drug cholangiocarcinoma treatment well defined aimed investigate potential clinical role gemcitabine metabolism related genes gemcitabine sensitivity cholangiocarcinoma identify characterize novel gemcitabine resistance related genes methods expressions genes related gemcitabine sensitivity gemcitabine metabolism measured 10 cholangiocarcinoma cell lines association gene expression gemcitabine sensitivity evaluated furthermore gemcitabine resistant cell lines established ysccc cells subjected genome wide microarray analysis 2 fold upregulated downregulated genes subjected pathway analysis results p53r2 mrna expression significantly higher gemcitabine resistant cell lines ic50 1000 nm subunits ribonucleotide reductase upregulated established gemcitabine resistant cell lines microarray analysis revealed upregulated genes resistant cells belonged glutathione pyrimidine metabolism pathways downregulated genes belonged n glycan biosynthesis pathway conclusions increased expression p53r2 may predict gemcitabine resistance upregulated rnr activity may influence gemcitabine resistance cholangiocarcinoma cells glutathione pathway related genes induced continuous exposure gemcitabine may contribute gemcitabine resistance google scholar","probabilities":0.9467213,"Title":"Gene Expression Analysis For Predicting Gemcitabine Resistance In Human Cholangiocarcinoma","Abstract":"Background\nGemcitabine is a promising drug for cholangiocarcinoma treatment. However, the kinetics and metabolism of this drug in cholangiocarcinoma treatment are not well defined. We aimed to investigate the potential clinical role of gemcitabine metabolism-related genes in the gemcitabine sensitivity of cholangiocarcinoma and identify and characterize novel gemcitabine resistance-related genes.\nMethods\nExpressions of genes related to gemcitabine sensitivity and gemcitabine metabolism were measured in 10 cholangiocarcinoma cell lines, and the association between gene expression and gemcitabine sensitivity was evaluated. Furthermore, gemcitabine-resistant cell lines were established from YSCCC cells and subjected to genome-wide microarray analysis. The 2-fold upregulated and downregulated genes were then subjected to pathway analysis.\nResults\np53R2 mRNA expression was significantly higher in gemcitabine-resistant cell lines (IC50 > 1000 nM), and all subunits of ribonucleotide reductase were upregulated in the established gemcitabine-resistant cell lines. Microarray analysis revealed that the upregulated genes in the resistant cells belonged to the glutathione and pyrimidine metabolism pathways, and that the downregulated genes belonged to the N-glycan biosynthesis pathway.\nConclusions\nIncreased expression of p53R2 may predict gemcitabine resistance, and upregulated RNR activity may influence gemcitabine resistance in cholangiocarcinoma cells. Glutathione pathway-related genes were induced by continuous exposure to gemcitabine and may contribute to gemcitabine resistance.","Source":"Google Scholar","category":"ANIMAL","training_data":"Gene Expression Analysis For Predicting Gemcitabine Resistance In Human Cholangiocarcinoma Background\nGemcitabine is a promising drug for cholangiocarcinoma treatment. However, the kinetics and metabolism of this drug in cholangiocarcinoma treatment are not well defined. We aimed to investigate the potential clinical role of gemcitabine metabolism-related genes in the gemcitabine sensitivity of cholangiocarcinoma and identify and characterize novel gemcitabine resistance-related genes.\nMethods\nExpressions of genes related to gemcitabine sensitivity and gemcitabine metabolism were measured in 10 cholangiocarcinoma cell lines, and the association between gene expression and gemcitabine sensitivity was evaluated. Furthermore, gemcitabine-resistant cell lines were established from YSCCC cells and subjected to genome-wide microarray analysis. The 2-fold upregulated and downregulated genes were then subjected to pathway analysis.\nResults\np53R2 mRNA expression was significantly higher in gemcitabine-resistant cell lines (IC50 > 1000 nM), and all subunits of ribonucleotide reductase were upregulated in the established gemcitabine-resistant cell lines. Microarray analysis revealed that the upregulated genes in the resistant cells belonged to the glutathione and pyrimidine metabolism pathways, and that the downregulated genes belonged to the N-glycan biosynthesis pathway.\nConclusions\nIncreased expression of p53R2 may predict gemcitabine resistance, and upregulated RNR activity may influence gemcitabine resistance in cholangiocarcinoma cells. Glutathione pathway-related genes were induced by continuous exposure to gemcitabine and may contribute to gemcitabine resistance. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"prognostic factors patients advanced gallbladder carcinoma following aggressive surgical resection background prognosis patients advanced gallbladder carcinoma dismal despite aggressive surgical resection aim study determine useful prognostic factors patients gallbladder carcinoma following aggressive surgical resection methods medical records 62 patients gallbladder carcinoma underwent surgical resection retrospectively reviewed univariate multivariate models used analyze effect clinicopathological factors long term survival results according uicc staging system ten 16 11 18 eight 13 16 25 nine 15 eight patients 13 diagnosed stages ii iiia iiib iva ivb disease respectively partial hepatectomy pancreatoduodenectomy performed 43 69 11 18 patients respectively overall survival rates 62 41 patients uicc stages iii iv disease 71 56 1 year 48 23 3 years 48 23 5 years respectively median survival time 15 8 12 7 months respectively multivariate analysis revealed independent prognostic factors included tumor differentiation p 0 006 hepatic invasion p 0 002 lymph node metastasis p 0 009 surgical margin status p 0 002 patients adjuvant chemotherapy p 0 005 tumor differentiation p 0 008 hepatic invasion p 0 001 surgical margin status p 0 022 patients uicc stages iii iv disease conclusions r0 resection adjuvant chemotherapy significant prognostic factors advanced gallbladder carcinoma performed improve survival pubmed","probabilities":0.9799733,"Title":"Prognostic factors of patients with advanced gallbladder carcinoma following aggressive surgical resection","Abstract":"BACKGROUND: The prognosis for patients with advanced gallbladder carcinoma is dismal despite aggressive surgical resection. The aim of this study is to determine useful prognostic factors for patients with gallbladder carcinoma following aggressive surgical resection. METHODS: Medical records of 62 patients with gallbladder carcinoma who underwent surgical resection were retrospectively reviewed. Univariate and multivariate models were used to analyze the effect of clinicopathological factors on long-term survival. RESULTS: According to the UICC staging system, ten (16%), 11 (18%), eight (13%), 16 (25%), nine (15%), and eight patients (13%) were diagnosed with stages I, II, IIIA, IIIB, IVA, and IVB disease, respectively. Partial hepatectomy and pancreatoduodenectomy were performed for 43 (69%) and 11 (18%) patients, respectively. Overall survival rates of all 62 and 41 patients with UICC stages III and IV disease were 71% and 56% at 1 year, 48% and 23% at 3 years, and 48% and 23% at 5 years, respectively (median survival time, 15.8 and 12.7 months, respectively). Multivariate analysis revealed that independent prognostic factors included tumor differentiation (p = 0.006), hepatic invasion (p = 0.002), lymph node metastasis (p = 0.009), and surgical margin status (p = 0.002) for all patients, and adjuvant chemotherapy (p = 0.005), tumor differentiation (p = 0.008), hepatic invasion (p = 0.001), and surgical margin status (p = 0.022) for patients with UICC stages III and IV disease. CONCLUSIONS: R0 resection and adjuvant chemotherapy are significant prognostic factors in advanced gallbladder carcinoma and should be performed to improve survival.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors of patients with advanced gallbladder carcinoma following aggressive surgical resection BACKGROUND: The prognosis for patients with advanced gallbladder carcinoma is dismal despite aggressive surgical resection. The aim of this study is to determine useful prognostic factors for patients with gallbladder carcinoma following aggressive surgical resection. METHODS: Medical records of 62 patients with gallbladder carcinoma who underwent surgical resection were retrospectively reviewed. Univariate and multivariate models were used to analyze the effect of clinicopathological factors on long-term survival. RESULTS: According to the UICC staging system, ten (16%), 11 (18%), eight (13%), 16 (25%), nine (15%), and eight patients (13%) were diagnosed with stages I, II, IIIA, IIIB, IVA, and IVB disease, respectively. Partial hepatectomy and pancreatoduodenectomy were performed for 43 (69%) and 11 (18%) patients, respectively. Overall survival rates of all 62 and 41 patients with UICC stages III and IV disease were 71% and 56% at 1 year, 48% and 23% at 3 years, and 48% and 23% at 5 years, respectively (median survival time, 15.8 and 12.7 months, respectively). Multivariate analysis revealed that independent prognostic factors included tumor differentiation (p = 0.006), hepatic invasion (p = 0.002), lymph node metastasis (p = 0.009), and surgical margin status (p = 0.002) for all patients, and adjuvant chemotherapy (p = 0.005), tumor differentiation (p = 0.008), hepatic invasion (p = 0.001), and surgical margin status (p = 0.022) for patients with UICC stages III and IV disease. CONCLUSIONS: R0 resection and adjuvant chemotherapy are significant prognostic factors in advanced gallbladder carcinoma and should be performed to improve survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival pancreaticoduodenectomy ampullary cancer affected age background although pancreaticoduodenectomy pd provides best chance survival elderly patients ampullary carcinoma associated considerable surgical risk aim present study compare benefits risks pancreaticoduodenectomy treatment ampullary carcinoma young elderly patients patients methods retrospectively reviewed medical records 171 consecutive patients treated hospital comparison biological aggressiveness ampullary cancer old younger patients also performed immunohistochemical study several prognostic biological markers including muc1 muc2 ck17 cdx2 results patients ampullary carcinoma presumed resectable preoperatively actuarial survival significantly poorer 55 elderly patients 9 pd 46 pd 101 younger patients pd multivariate analysis indicated pd independent prognostic factor age significant differences muc1 ck17 muc2 cdx2 immunohistochemical staining ampullary carcinomas elderly young patients spite increased co morbidities pd performed safely elderly patients young patients pd actuarial survival similar old young patients conclusions data support conclusion ampullary cancers elderly patients treated aggressively younger patients pubmed","probabilities":0.9799733,"Title":"Survival after pancreaticoduodenectomy for ampullary cancer is not affected by age","Abstract":"BACKGROUND: Although pancreaticoduodenectomy (PD) provides the best chance of survival for elderly patients with ampullary carcinoma, it is associated with considerable surgical risk. The aim of the present study was to compare the benefits and risks of pancreaticoduodenectomy as a treatment of ampullary carcinoma between young and elderly patients. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 171 consecutive patients treated at our hospital. Comparison of the biological aggressiveness of ampullary cancer between old and younger patients was also performed by immunohistochemical study of several prognostic biological markers, including MUC1, MUC2, CK17, and CDX2. RESULTS: For patients in whom ampullary carcinoma was presumed resectable preoperatively, actuarial survival was significantly poorer in 55 elderly patients because 9 of them did not have PD (the other 46 had PD) than in 101 younger patients (all had PD). Multivariate analysis indicated that PD was the only independent prognostic factor; age was not. There were no significant differences in MUC1, CK17, MUC2, and CDX2 immunohistochemical staining of ampullary carcinomas between elderly and young patients. In spite of increased co-morbidities, PD could be performed as safely in elderly patients as in young patients. After PD, the actuarial survival was similar between old and young patients. CONCLUSIONS: Our data support the conclusion that ampullary cancers in elderly patients should be treated as aggressively as in younger patients.","Source":"PubMed","category":"HUMAN","training_data":"Survival after pancreaticoduodenectomy for ampullary cancer is not affected by age BACKGROUND: Although pancreaticoduodenectomy (PD) provides the best chance of survival for elderly patients with ampullary carcinoma, it is associated with considerable surgical risk. The aim of the present study was to compare the benefits and risks of pancreaticoduodenectomy as a treatment of ampullary carcinoma between young and elderly patients. PATIENTS AND METHODS: We retrospectively reviewed the medical records of 171 consecutive patients treated at our hospital. Comparison of the biological aggressiveness of ampullary cancer between old and younger patients was also performed by immunohistochemical study of several prognostic biological markers, including MUC1, MUC2, CK17, and CDX2. RESULTS: For patients in whom ampullary carcinoma was presumed resectable preoperatively, actuarial survival was significantly poorer in 55 elderly patients because 9 of them did not have PD (the other 46 had PD) than in 101 younger patients (all had PD). Multivariate analysis indicated that PD was the only independent prognostic factor; age was not. There were no significant differences in MUC1, CK17, MUC2, and CDX2 immunohistochemical staining of ampullary carcinomas between elderly and young patients. In spite of increased co-morbidities, PD could be performed as safely in elderly patients as in young patients. After PD, the actuarial survival was similar between old and young patients. CONCLUSIONS: Our data support the conclusion that ampullary cancers in elderly patients should be treated as aggressively as in younger patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison overall survival gallbladder carcinoma academic versus community cancer centers analysis national cancer data base background objectives gallbladder carcinoma gbc poor prognosis studies demonstrated teaching facilities may provide lower risk mortality patients undergoing pancreatic colon resection vs nonteaching facilities hypothesized survival rates higher academic cancer centers accs vs community cancer centers cccs methods patients stages gbc identified national cancer database 2007 2012 propensity score matching adjusted selection bias descriptive statistics calculated variables overall survival os compared facility type acc vs ccc case volume low vs high via multivariable cox proportional hazards regression results total 7967 patients met inclusion criteria following propensity matching 2801 patients analyzed facility type median os following surgery higher acc 20 99 months 95 confidence interval ci 19 61 22 64 p 002 ccc 17 68 months 95 ci 16 46 19 25 following cox modeling gbc treatment accs protective factor os adjusted hazard ratio 0 876 95 ci 0 801 0 958 p 004 discussion gbc treatment accs independent predictor os high volume accs associated improved os compared low volume accs site care case volume accs may contribute improved survival outcomes stn","probabilities":0.9799733,"Title":"Comparison Of Overall Survival In Gallbladder Carcinoma At Academic Versus Community Cancer Centers: An Analysis Of The National Cancer Data Base","Abstract":"Background and objectives: Gallbladder carcinoma (GBC) has a poor prognosis. Studies demonstrated that teaching facilities may provide a lower risk of mortality in patients undergoing pancreatic and colon resection vs nonteaching facilities. We hypothesized that survival rates are higher in academic cancer centers (ACCs) vs community cancer centers (CCCs). \r\n\r\n Methods: Patients with all stages of GBC were identified from the National Cancer Database (2007-2012). Propensity score matching adjusted for selection bias. Descriptive statistics were calculated for all variables. Overall survival (OS) was compared by facility type (ACC vs CCC) and case volume (low vs high) via multivariable Cox proportional hazards regression. \r\n\r\n Results: A total of 7967 patients met the inclusion criteria. Following propensity matching, 2801 patients were analyzed from each facility type. Median OS following surgery was higher for ACC (20.99 months, 95% confidence interval [CI], 19.61-22.64, P = .002) than CCC (17.68 months, 95% CI, 16.46-19.25). Following Cox modeling, GBC treatment at ACCs was a protective factor for OS (adjusted hazard ratio 0.876, 95% CI, 0.801-0.958, P = .004). \r\n\r\n Discussion: GBC treatment at ACCs is an independent predictor of OS. High volume ACCs are associated with improved OS compared with low volume ACCs. The site of care and case volume in ACCs may contribute to improved survival outcomes.","Source":"STN","category":"HUMAN","training_data":"Comparison Of Overall Survival In Gallbladder Carcinoma At Academic Versus Community Cancer Centers: An Analysis Of The National Cancer Data Base Background and objectives: Gallbladder carcinoma (GBC) has a poor prognosis. Studies demonstrated that teaching facilities may provide a lower risk of mortality in patients undergoing pancreatic and colon resection vs nonteaching facilities. We hypothesized that survival rates are higher in academic cancer centers (ACCs) vs community cancer centers (CCCs). \r\n\r\n Methods: Patients with all stages of GBC were identified from the National Cancer Database (2007-2012). Propensity score matching adjusted for selection bias. Descriptive statistics were calculated for all variables. Overall survival (OS) was compared by facility type (ACC vs CCC) and case volume (low vs high) via multivariable Cox proportional hazards regression. \r\n\r\n Results: A total of 7967 patients met the inclusion criteria. Following propensity matching, 2801 patients were analyzed from each facility type. Median OS following surgery was higher for ACC (20.99 months, 95% confidence interval [CI], 19.61-22.64, P = .002) than CCC (17.68 months, 95% CI, 16.46-19.25). Following Cox modeling, GBC treatment at ACCs was a protective factor for OS (adjusted hazard ratio 0.876, 95% CI, 0.801-0.958, P = .004). \r\n\r\n Discussion: GBC treatment at ACCs is an independent predictor of OS. High volume ACCs are associated with improved OS compared with low volume ACCs. The site of care and case volume in ACCs may contribute to improved survival outcomes. STN","prediction_labels":"HUMAN"},{"cleaned":"aspirin may extend biliary tract cancer survival results populationbased cohort background biliary tract cancers btcs rare lethal cancers median survival 12 months poor prognosis critical need treatments extend survival cyclooxygenase 2 cox 2 enzyme responsible producing prostaglandin e pge pges increase mucin production reduce bile flow gallbladder leading gallstones precursor gallbladder cancer overexpression cox 2 due chronic inflammation cholangiocarcinoma found enhance pge production promote tumor growth previous research suggests cox 2 inhibitors aspirin may slow cancer cell growth investigated aspirin use following diagnosis overall survival large cohort patients btcs methods patients diagnosed incident biliary tract cancer 1990 2017 selected population based united kingdom clinical practice research datalink site specific associations aspirin use btc diagnosis overall survival analyzed using cox proportional hazards models aspirin use modeled time dependent adjusting age diagnosis sex comorbidities history aspirin use use statins using follow time time scale results identified 3 211 biliary tract cancer cases 2 694 84 deaths occurred overall median follow time 5 months table presents number cases cancer subtype deaths median survival time aspirin use following diagnosis btc associated reduction mortality btc sites gallbladder hr 0 41 95 ci 0 28 0 61 cholangiocarcinoma hr 0 46 95 ci 0 36 0 60 ampulla vater hr 0 24 95 ci 0 11 0 51 mixed hr 0 51 95 ci 0 33 0 78 conclusions use aspirin btc diagnosis associated lower risk overall mortality results warrant additional studies understand mechanisms underlying improved survival aspirin use google scholar","probabilities":1.0,"Title":"Aspirin May Extend Biliary Tract Cancer Survival: Results From Populationbased Cohort","Abstract":"Background: Biliary tract cancers (BTCs) are rare, but lethal cancers with a median survival of <12 months. Because of this poor prognosis, there is a critical need for treatments that extend survival. Cyclooxygenase-2 (COX-2) is an enzyme responsible for producing prostaglandin E (PGE). PGEs increase mucin production and reduce bile flow in the gallbladder, leading to gallstones, a precursor to gallbladder cancer. Overexpression of COX-2 due to chronic inflammation from cholangiocarcinoma has been found to enhance PGE production and promote tumor growth. Previous research suggests that COX-2 inhibitors, such as aspirin, may slow cancer cell growth. We investigated aspirin use following diagnosis and overall survival in a large cohort of patients with BTCs.\nMethods: All patients diagnosed with incident biliary tract cancer between 1990 to 2017 were selected from the population-based United Kingdom’s Clinical Practice Research Datalink. Site-specific associations between aspirin use after BTC diagnosis and overall survival was analyzed using Cox proportional hazards models with aspirin use modeled as time-dependent, adjusting for age at diagnosis, sex, comorbidities, history of aspirin use, and use of statins, using follow-up time as the time scale.\nResults: We identified 3,211 biliary tract cancer cases in which 2,694 (84%) deaths occurred after an overall median follow-up time of 5 months. The table presents the number of cases by cancer subtype, deaths, and median survival time. Aspirin use following a diagnosis of BTC was associated with a reduction in mortality for each of the BTC sites: gallbladder, HR 0.41 (95% CI: 0.28, 0.61); cholangiocarcinoma, HR 0.46 (95% CI: 0.36, 0.60); ampulla of Vater, HR 0.24 (95% CI: 0.11, 0.51); and mixed, HR: 0.51 (95% CI: 0.33, 0.78).\nConclusions: The use of aspirin after BTC diagnosis was associated with a lower risk of overall mortality. These results warrant additional studies to understand the mechanisms underlying improved survival with aspirin use.","Source":"Google Scholar","category":"HUMAN","training_data":"Aspirin May Extend Biliary Tract Cancer Survival: Results From Populationbased Cohort Background: Biliary tract cancers (BTCs) are rare, but lethal cancers with a median survival of <12 months. Because of this poor prognosis, there is a critical need for treatments that extend survival. Cyclooxygenase-2 (COX-2) is an enzyme responsible for producing prostaglandin E (PGE). PGEs increase mucin production and reduce bile flow in the gallbladder, leading to gallstones, a precursor to gallbladder cancer. Overexpression of COX-2 due to chronic inflammation from cholangiocarcinoma has been found to enhance PGE production and promote tumor growth. Previous research suggests that COX-2 inhibitors, such as aspirin, may slow cancer cell growth. We investigated aspirin use following diagnosis and overall survival in a large cohort of patients with BTCs.\nMethods: All patients diagnosed with incident biliary tract cancer between 1990 to 2017 were selected from the population-based United Kingdom’s Clinical Practice Research Datalink. Site-specific associations between aspirin use after BTC diagnosis and overall survival was analyzed using Cox proportional hazards models with aspirin use modeled as time-dependent, adjusting for age at diagnosis, sex, comorbidities, history of aspirin use, and use of statins, using follow-up time as the time scale.\nResults: We identified 3,211 biliary tract cancer cases in which 2,694 (84%) deaths occurred after an overall median follow-up time of 5 months. The table presents the number of cases by cancer subtype, deaths, and median survival time. Aspirin use following a diagnosis of BTC was associated with a reduction in mortality for each of the BTC sites: gallbladder, HR 0.41 (95% CI: 0.28, 0.61); cholangiocarcinoma, HR 0.46 (95% CI: 0.36, 0.60); ampulla of Vater, HR 0.24 (95% CI: 0.11, 0.51); and mixed, HR: 0.51 (95% CI: 0.33, 0.78).\nConclusions: The use of aspirin after BTC diagnosis was associated with a lower risk of overall mortality. These results warrant additional studies to understand the mechanisms underlying improved survival with aspirin use. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"anti malarial drugs artesunate chloroquine induce cell death different mechanisms bile duct cancer cell lines background pathogenesis cholangiocarcinoma cca malignancy bile duct epithelial cells multifactorial cca northeast thailand associated chronic inflammation due liver fluke opisthorchis viverrini ov infection since chemotherapy ov associated cca quite successful revisited efficacy antimalarial drugs artesunate art chloroquine cq cca art cq explored among anti parasitic drugs anti cancer effects shown potential inhibiting cell growth inducing cell death various cancer cells art cq induce cell death malaria parasite similar mechanism depending upon formation reactive oxygen species ros thus great interest study whether cell death mechanisms bile duct cancer cells treatment art cq similar different methods effects art cq studied bile duct cancer cell lines m214l0 m214l5 cell proliferation treatment art cq studied wst assay phenotypic cell death pattern studied using time lapse analysis results art cq inhibited proliferation bile duct cancer cell lines m214l0 m214l5 dose time dependent manner regarding phenotypic pattern cell death art induced necrosis whereas cq induced apoptosis bile duct cancer cell lines conclusion art cq induce cell death bile duct cancer cell lines via different mechanisms however different cell death patterns induced art cq need explored molecular phenotypic level google scholar","probabilities":0.9467213,"Title":"Anti-Malarial Drugs Artesunate And Chloroquine Induce Cell Death By Different Mechanisms In Bile Duct Cancer Cell Lines","Abstract":"Background: Pathogenesis of cholangiocarcinoma (CCA), a\nmalignancy of bile duct epithelial cells, is multifactorial.\nCCA in the Northeast Thailand is associated with chronic\ninflammation due to liver fluke (Opisthorchis viverrini, OV) infection. Since chemotherapy for OV-associated CCA is not\nquite successful, we revisited the efficacy of antimalarial\ndrugs, artesunate (ART) and chloroquine (CQ), against CCA.\nART and CQ are the most explored among anti-parasitic\ndrugs for their anti-cancer effects and have shown potential\nof inhibiting cell growth and inducing cell death in various\ncancer cells. ART and CQ, both induce cell death of malaria\nparasite by a similar mechanism depending upon formation\nof reactive oxygen species (ROS). Thus, it is of great interest\nto study whether the cell death mechanisms of bile duct\ncancer cells after treatment with ART and CQ are similar or\ndifferent. Methods: The effects of ART and CQ were studied\non bile duct cancer cell lines M214L0 and M214L5. Cell\nproliferation after treatment with ART and CQ was studied\nby WST assay. The phenotypic cell death pattern was studied\nusing time-lapse analysis. Results: Both ART and CQ\ninhibited proliferation of bile duct cancer cell lines M214L0\nand M214L5 in a dose- and time-dependent manner.\nRegarding the phenotypic pattern of cell death, ART induced\nnecrosis, whereas CQ induced apoptosis, against both bile\nduct cancer cell lines. Conclusion: ART and CQ induce cell\ndeath in bile duct cancer cell lines via different mechanisms.\nHowever, the different cell death patterns induced by ART\nand CQ need to be further explored at the molecular\nphenotypic level.","Source":"Google Scholar","category":"ANIMAL","training_data":"Anti-Malarial Drugs Artesunate And Chloroquine Induce Cell Death By Different Mechanisms In Bile Duct Cancer Cell Lines Background: Pathogenesis of cholangiocarcinoma (CCA), a\nmalignancy of bile duct epithelial cells, is multifactorial.\nCCA in the Northeast Thailand is associated with chronic\ninflammation due to liver fluke (Opisthorchis viverrini, OV) infection. Since chemotherapy for OV-associated CCA is not\nquite successful, we revisited the efficacy of antimalarial\ndrugs, artesunate (ART) and chloroquine (CQ), against CCA.\nART and CQ are the most explored among anti-parasitic\ndrugs for their anti-cancer effects and have shown potential\nof inhibiting cell growth and inducing cell death in various\ncancer cells. ART and CQ, both induce cell death of malaria\nparasite by a similar mechanism depending upon formation\nof reactive oxygen species (ROS). Thus, it is of great interest\nto study whether the cell death mechanisms of bile duct\ncancer cells after treatment with ART and CQ are similar or\ndifferent. Methods: The effects of ART and CQ were studied\non bile duct cancer cell lines M214L0 and M214L5. Cell\nproliferation after treatment with ART and CQ was studied\nby WST assay. The phenotypic cell death pattern was studied\nusing time-lapse analysis. Results: Both ART and CQ\ninhibited proliferation of bile duct cancer cell lines M214L0\nand M214L5 in a dose- and time-dependent manner.\nRegarding the phenotypic pattern of cell death, ART induced\nnecrosis, whereas CQ induced apoptosis, against both bile\nduct cancer cell lines. Conclusion: ART and CQ induce cell\ndeath in bile duct cancer cell lines via different mechanisms.\nHowever, the different cell death patterns induced by ART\nand CQ need to be further explored at the molecular\nphenotypic level. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"radiological findings surgical outcomes pulmonary metastases originating biliary tract carcinoma purpose metastasis lungs arising biliary tract carcinoma btc extremely rare patient characteristics prognosis well known aimed identify imaging findings pulmonary metastases originating btc eligible indications surgical treatment methods fifteen patients underwent pulmonary resection metastases originating btc retrospectively analyzed results primary sites included cholangiocarcinoma n 12 gallbladder carcinoma n 3 cases histologically diagnosed well moderately differentiated adenocarcinomas median disease free interval resection primary site detection pulmonary metastasis 30 months range 0 144 months nine patients single lesion six multiple lesions features pulmonary lesions thin section computed tomography ct many appeared solid nodules smooth margins whereas six lesions concomitant spiculation pleural indentation three air bronchogram ground glass attenuation one intra tumoral cavity six cases solitary pulmonary lesion diagnosed primary lung cancer metastasectomy 3 year survival rate 11 patients underwent complete metastasectomy 45 disease free interval 3 years p 0 03 single lesion p 0 01 significant prognostic factors conclusions ct findings pulmonary metastases btcs sometimes resemble characteristic findings primary lung cancer long disease free interval single lesion therefore considered good surgical indicators pubmed","probabilities":0.9799733,"Title":"Radiological findings and surgical outcomes of pulmonary metastases originating from biliary tract carcinoma","Abstract":"PURPOSE: Metastasis to the lungs arising from biliary tract carcinoma (BTC) is extremely rare, and the patient characteristics and prognosis are not well known. We aimed to identify the imaging findings of pulmonary metastases originating from BTC and the eligible indications for surgical treatment. METHODS: Fifteen patients who underwent pulmonary resection for metastases originating from BTC were retrospectively analyzed. RESULTS: The primary sites included cholangiocarcinoma (n = 12) and gallbladder carcinoma (n = 3), and all cases were histologically diagnosed as well to moderately differentiated adenocarcinomas. The median disease-free interval between resection for the primary site and the detection of pulmonary metastasis was 30 months (range 0-144 months). Nine patients had a single lesion, and six had multiple lesions. As features of pulmonary lesions on thin-section computed tomography (CT), many appeared as solid nodules with smooth margins, whereas six lesions were concomitant with spiculation or pleural indentation, three with air bronchogram or ground-glass attenuation, and one with intra-tumoral cavity, and six cases with solitary pulmonary lesion were diagnosed as primary lung cancer before metastasectomy. The 3-year survival rate in the 11 patients who underwent complete metastasectomy was 45%. A disease-free interval of more than 3 years (p = 0.03) and single lesion (p < 0.01) were significant prognostic factors. CONCLUSIONS: The CT findings of pulmonary metastases from BTCs sometimes resemble the characteristic findings of primary lung cancer. A long disease-free interval and single lesion are therefore considered to be good surgical indicators.","Source":"PubMed","category":"HUMAN","training_data":"Radiological findings and surgical outcomes of pulmonary metastases originating from biliary tract carcinoma PURPOSE: Metastasis to the lungs arising from biliary tract carcinoma (BTC) is extremely rare, and the patient characteristics and prognosis are not well known. We aimed to identify the imaging findings of pulmonary metastases originating from BTC and the eligible indications for surgical treatment. METHODS: Fifteen patients who underwent pulmonary resection for metastases originating from BTC were retrospectively analyzed. RESULTS: The primary sites included cholangiocarcinoma (n = 12) and gallbladder carcinoma (n = 3), and all cases were histologically diagnosed as well to moderately differentiated adenocarcinomas. The median disease-free interval between resection for the primary site and the detection of pulmonary metastasis was 30 months (range 0-144 months). Nine patients had a single lesion, and six had multiple lesions. As features of pulmonary lesions on thin-section computed tomography (CT), many appeared as solid nodules with smooth margins, whereas six lesions were concomitant with spiculation or pleural indentation, three with air bronchogram or ground-glass attenuation, and one with intra-tumoral cavity, and six cases with solitary pulmonary lesion were diagnosed as primary lung cancer before metastasectomy. The 3-year survival rate in the 11 patients who underwent complete metastasectomy was 45%. A disease-free interval of more than 3 years (p = 0.03) and single lesion (p < 0.01) were significant prognostic factors. CONCLUSIONS: The CT findings of pulmonary metastases from BTCs sometimes resemble the characteristic findings of primary lung cancer. A long disease-free interval and single lesion are therefore considered to be good surgical indicators. PubMed","prediction_labels":"HUMAN"},{"cleaned":"endoscopic biliary drainage patients cholangiocarcinoma self expanding metal versus polyethylene stents background endoscopic biliary drainage standard care patients cholangiocarcinoma cca induced obstructive jaundice self expanding metal stents supposed superior polyethylene stents terms reduction interventions costs far real life data respect stent selection survival patient cohort methods study retrospectively analyzed patients cca treated endoscopic biliary drainage 2000 2015 hannover medical school germany aim study analyze whether metal stenting reduces frequency interventions influences survival large real life cohort results overall 422 patients cca included study indication endoscopic biliary drainage often obstructive jaundice n 397 94 1 among patients 20 patients 5 initially treated metal stent 38 9 6 received metal stent subsequent course median number interventions per month 2 4 fold reduced following metal stenting patients first treated metal stent advanced tumor stage significantly shorter median overall survival mos compared patients received metal stent subsequently 7 5 months vs 15 2 months p 019 difference mos metal vs polyethylene stenting following propensity score match confounders curative resection chemotherapy 13 2 vs 13 7 months p 555 conclusions data confirm metal stenting reduces frequency interventions influence os metal stenting considered specifically younger patients suitable chemotherapy pubmed","probabilities":0.9799733,"Title":"Endoscopic biliary drainage in patients with cholangiocarcinoma - self-expanding metal versus polyethylene stents","Abstract":"Background: Endoscopic biliary drainage is the standard of care for patients with cholangiocarcinoma (CCA)-induced, obstructive jaundice. Self-expanding metal stents are supposed to be superior to polyethylene stents in terms of reduction of interventions and costs. So far, there are only few real-life data with respect to stent selection and survival in this patient cohort. Methods: In this study, we retrospectively analyzed patients with CCA treated with endoscopic biliary drainage from 2000 to 2015 at Hannover Medical School, Germany. The aim of this study was to analyze whether metal stenting reduces the frequency of interventions and influences survival in a large, real-life cohort. Results: Overall, 422 patients with CCA were included in this study. Indication for endoscopic biliary drainage was most often obstructive jaundice (n = 397; 94.1%). Among these patients, 20 patients (5%) were initially treated with a metal stent and 38 (9.6%) received a metal stent in the subsequent course. Median number of interventions per month was 2.4-fold reduced following metal stenting. Patients first treated with a metal stent had a more advanced tumor stage and a significantly shorter median overall survival (mOS) compared to patients who received a metal stent subsequently (7.5 months vs. 15.2 months; p=.019). There was no difference in mOS for metal vs. polyethylene stenting following a propensity score match for the confounders curative resection and chemotherapy (13.2 vs. 13.7 months, p=.555). Conclusions: Our data confirm that metal stenting reduces the frequency of interventions, but does not influence OS. Metal stenting should be considered specifically in younger patients who are suitable for chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Endoscopic biliary drainage in patients with cholangiocarcinoma - self-expanding metal versus polyethylene stents Background: Endoscopic biliary drainage is the standard of care for patients with cholangiocarcinoma (CCA)-induced, obstructive jaundice. Self-expanding metal stents are supposed to be superior to polyethylene stents in terms of reduction of interventions and costs. So far, there are only few real-life data with respect to stent selection and survival in this patient cohort. Methods: In this study, we retrospectively analyzed patients with CCA treated with endoscopic biliary drainage from 2000 to 2015 at Hannover Medical School, Germany. The aim of this study was to analyze whether metal stenting reduces the frequency of interventions and influences survival in a large, real-life cohort. Results: Overall, 422 patients with CCA were included in this study. Indication for endoscopic biliary drainage was most often obstructive jaundice (n = 397; 94.1%). Among these patients, 20 patients (5%) were initially treated with a metal stent and 38 (9.6%) received a metal stent in the subsequent course. Median number of interventions per month was 2.4-fold reduced following metal stenting. Patients first treated with a metal stent had a more advanced tumor stage and a significantly shorter median overall survival (mOS) compared to patients who received a metal stent subsequently (7.5 months vs. 15.2 months; p=.019). There was no difference in mOS for metal vs. polyethylene stenting following a propensity score match for the confounders curative resection and chemotherapy (13.2 vs. 13.7 months, p=.555). Conclusions: Our data confirm that metal stenting reduces the frequency of interventions, but does not influence OS. Metal stenting should be considered specifically in younger patients who are suitable for chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival ampullary cancer potential role different kras mutations objective prognosis ampullary adenocarcinoma aa usually favorable however subset aa poor biology outcomes similar pancreatic cancer patients subset early recurrence death usually within 2 years date genetic markers identify patients study identifies high risk subset aa evaluates mutational status kras predicting poor outcome methods tumor registry academic center reviewed data patients managed operatively aa kras genotypes determined patients using polymerase chain reaction based assay clinical specimens analysis variance 2 tests used categorize continuous categorical variables univariate multivariate survival analyses performed using kaplan meier cox methods respectively results total 146 patients identified aa 1982 2008 stringent pathologic review 97 patients confirmed aa 75 tissue specimens available analysis genotyping revealed 67 wild type kras wt 33 mutant kras patients kras g12d n 9 common mutational genotype poorer median survival 62 months compared kras non g12d mutants median survival reached mean 145 months kras wt patients 155 months p 05 patients survival 30 months labeled high risk 9 patients kras g12d 56 high risk subset compared 18 kras wt p 02 31 kras non g12d p 05 populations patients kras g12d also likely present advanced stage conclusion kras g12d mutation identifies subset aa patients poor prognoses may used identify patients risk early recurrence poorer survival may benefit adjuvant therapy pubmed","probabilities":0.7966102,"Title":"Survival in ampullary cancer: potential role of different KRAS mutations","Abstract":"OBJECTIVE: The prognosis of ampullary adenocarcinoma (AA) usually is favorable; however, a subset of AA have poor biology and outcomes similar to pancreatic cancer. Patients in this subset will have early recurrence and death usually within 2 years. To date, there are no genetic markers to identify these patients. This study identifies the high-risk subset of AA and evaluates the mutational status of KRAS in predicting poor outcome. METHODS: The tumor registry of an academic center was reviewed for data on patients managed operatively with AA. KRAS genotypes were determined for these patients using a polymerase chain reaction-based assay on clinical specimens. Analysis of variance and χ(2) tests was used to categorize continuous and categorical variables. Univariate and multivariate survival analyses were performed using Kaplan-Meier and Cox methods, respectively. RESULTS: A total of 146 patients were identified with AA between 1982 and 2008. After stringent pathologic review, 97 patients were confirmed with AA, of whom 75 had tissue specimens available for analysis. Genotyping revealed 67% were wild-type (KRAS(WT)), and 33% were mutant for KRAS. Patients with KRAS(G12D) (n = 9), the most common mutational genotype, had poorer median survival (62 months) compared with those with KRAS(non-G12D) mutants (median survival not reached, mean 145 months) and KRAS(WT) patients (155 months, P = .05). Patients with survival ≤30 months were labeled \"high-risk.\" Of the 9 patients with KRAS(G12D), 56% were in this high-risk subset, compared with 18% of KRAS(WT) (P = .02) and 31% of KRAS(non-G12D) (P > .05) populations. Patients with KRAS(G12D) also were more likely to present with advanced T stage. CONCLUSION: The KRAS(G12D) mutation identifies a subset of AA patients with poor prognoses and may be used to identify patients at risk of early recurrence and poorer survival who may benefit from adjuvant therapy.","Source":"PubMed","category":"HUMAN","training_data":"Survival in ampullary cancer: potential role of different KRAS mutations OBJECTIVE: The prognosis of ampullary adenocarcinoma (AA) usually is favorable; however, a subset of AA have poor biology and outcomes similar to pancreatic cancer. Patients in this subset will have early recurrence and death usually within 2 years. To date, there are no genetic markers to identify these patients. This study identifies the high-risk subset of AA and evaluates the mutational status of KRAS in predicting poor outcome. METHODS: The tumor registry of an academic center was reviewed for data on patients managed operatively with AA. KRAS genotypes were determined for these patients using a polymerase chain reaction-based assay on clinical specimens. Analysis of variance and χ(2) tests was used to categorize continuous and categorical variables. Univariate and multivariate survival analyses were performed using Kaplan-Meier and Cox methods, respectively. RESULTS: A total of 146 patients were identified with AA between 1982 and 2008. After stringent pathologic review, 97 patients were confirmed with AA, of whom 75 had tissue specimens available for analysis. Genotyping revealed 67% were wild-type (KRAS(WT)), and 33% were mutant for KRAS. Patients with KRAS(G12D) (n = 9), the most common mutational genotype, had poorer median survival (62 months) compared with those with KRAS(non-G12D) mutants (median survival not reached, mean 145 months) and KRAS(WT) patients (155 months, P = .05). Patients with survival ≤30 months were labeled \"high-risk.\" Of the 9 patients with KRAS(G12D), 56% were in this high-risk subset, compared with 18% of KRAS(WT) (P = .02) and 31% of KRAS(non-G12D) (P > .05) populations. Patients with KRAS(G12D) also were more likely to present with advanced T stage. CONCLUSION: The KRAS(G12D) mutation identifies a subset of AA patients with poor prognoses and may be used to identify patients at risk of early recurrence and poorer survival who may benefit from adjuvant therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative prognostic model predict surgical success patients perihilar cholangiocarcinoma background patients resectable perihilar cholangiocarcinoma phc imaging substantial risk metastatic locally advanced disease incomplete r1 resection 90 day mortality aim develop preoperative prognostic model predict surgical success defined complete r0 resection without 90 day mortality patients resectable phc imaging study design patients phc underwent exploratory laparotomy three tertiary referral centers identified multivariable logistic regression performed identify preoperatively available prognostic factors prognostic model developed using data two european centers validated one american center results total 671 patients phc underwent exploratory laparotomy derivation cohort surgical success achieved 102 331 patients 30 8 resection performed 176 patients 53 2 metastatic locally advanced disease 155 patients 46 8 underwent resection 38 24 5 r1 resection remaining 117 35 3 15 12 8 90 day mortality independent poor prognostic factors surgical success identified preoperative prognostic model developed concordance index 0 71 external validation showed good concordance 0 70 conclusion surgical success achieved 30 patients phc undergoing exploratory laparotomy predicted age cholangitis hepatic artery involvement lymph node metastases blumgart stage stn","probabilities":0.9799733,"Title":"Preoperative Prognostic Model To Predict Surgical Success In Patients With Perihilar Cholangiocarcinoma","Abstract":"Background: Patients with resectable perihilar cholangiocarcinoma (PHC) on imaging have a substantial risk of metastatic or locally advanced disease, incomplete (R1) resection, and 90-day mortality. Our aim was to develop a preoperative prognostic model to predict surgical success, defined as a complete (R0) resection without 90-day mortality, in patients with resectable PHC on imaging. \r\n\r\n Study design: Patients with PHC who underwent exploratory laparotomy in three tertiary referral centers were identified. Multivariable logistic regression was performed to identify preoperatively available prognostic factors. A prognostic model was developed using data from two European centers and validated in one American center. \r\n\r\n Results: In total, 671 patients with PHC underwent exploratory laparotomy. In the derivation cohort, surgical success was achieved in 102 of 331 patients (30.8%). No resection was performed in 176 patients (53.2%) because of metastatic or locally advanced disease. Of the 155 patients (46.8%) who underwent a resection, 38 (24.5%) had an R1-resection. Of the remaining 117 (35.3%), 15 (12.8%) had 90-day mortality. Independent poor prognostic factors for surgical success were identified, and a preoperative prognostic model was developed with a concordance index of 0.71. External validation showed good concordance (0.70). \r\n\r\n Conclusion: Surgical success was achieved in only 30% of patients with PHC undergoing exploratory laparotomy and could be predicted by age, cholangitis, hepatic artery involvement, lymph node metastases, and Blumgart stage.","Source":"STN","category":"HUMAN","training_data":"Preoperative Prognostic Model To Predict Surgical Success In Patients With Perihilar Cholangiocarcinoma Background: Patients with resectable perihilar cholangiocarcinoma (PHC) on imaging have a substantial risk of metastatic or locally advanced disease, incomplete (R1) resection, and 90-day mortality. Our aim was to develop a preoperative prognostic model to predict surgical success, defined as a complete (R0) resection without 90-day mortality, in patients with resectable PHC on imaging. \r\n\r\n Study design: Patients with PHC who underwent exploratory laparotomy in three tertiary referral centers were identified. Multivariable logistic regression was performed to identify preoperatively available prognostic factors. A prognostic model was developed using data from two European centers and validated in one American center. \r\n\r\n Results: In total, 671 patients with PHC underwent exploratory laparotomy. In the derivation cohort, surgical success was achieved in 102 of 331 patients (30.8%). No resection was performed in 176 patients (53.2%) because of metastatic or locally advanced disease. Of the 155 patients (46.8%) who underwent a resection, 38 (24.5%) had an R1-resection. Of the remaining 117 (35.3%), 15 (12.8%) had 90-day mortality. Independent poor prognostic factors for surgical success were identified, and a preoperative prognostic model was developed with a concordance index of 0.71. External validation showed good concordance (0.70). \r\n\r\n Conclusion: Surgical success was achieved in only 30% of patients with PHC undergoing exploratory laparotomy and could be predicted by age, cholangitis, hepatic artery involvement, lymph node metastases, and Blumgart stage. STN","prediction_labels":"HUMAN"},{"cleaned":"oncologic outcomes extended lymphadenectomy without liver resection t1 t2 gallbladder cancer purpose study provides standardized operative strategical algorithm applied patients t1 t2 gallbladder cancer gbc aim determine oncologic outcome radical cholecystectomy para aortic lymph node dissection without liver resection t1 t2 gbc materials methods january 2005 december 2017 164 patients gbc underwent operations single surgeon severance hospital retrospective review performed 113 patients pathologically determined stages t1 t2 according american joint committee cancer 7th guidelines results 113 patients 109 underwent curative resection t1 t2 gbc four patients underwent palliative operations without radical cholecystectomies excluded analyses t1b t2 lesions radical cholecystectomy para aortic lymph node dissection performed without liver resection four gbc related mortalities 5 year disease specific survival 97 0 median follow 50 months range 5 145 months stages median reached survival analysis five year disease specific survival t1a t1b t2 100 94 1 97 1 respectively five year disease free survival t1a t1b t2 100 87 0 91 8 respectively conclusion results suggest current operative protocol applied minimal invasive operations gbc similar oncologic outcomes open approach t1 t2 gbc radical cholecystectomy including para aortic lymph node dissection performed safely favorable oncologic outcomes pubmed","probabilities":0.9799733,"Title":"Oncologic Outcomes of Extended Lymphadenectomy without Liver Resection for T1/T2 Gallbladder Cancer","Abstract":"PURPOSE: This study provides a standardized operative strategical algorithm that can be applied to patients with T1/T2 gallbladder cancer (GBC). Our aim was to determine the oncologic outcome of radical cholecystectomy with para-aortic lymph node dissection without liver resection in T1/T2 GBC. MATERIALS AND METHODS: From January 2005 to December 2017, 164 patients with GBC underwent operations by a single surgeon at Severance Hospital. A retrospective review was performed for 113 of these patients, who were pathologically determined to be in stages T1 and T2 according to American Joint Committee on Cancer 7th guidelines. RESULTS: Of the 113 patients, 109 underwent curative resection for T1/T2 GBC; four patients who underwent palliative operations without radical cholecystectomies were excluded from further analyses. For all T1b and T2 lesions, radical cholecystectomy with para-aortic lymph node dissection was performed without liver resection. There were four GBC-related mortalities, and 5-year disease-specific survival was 97.0%. The median follow-up was 50 months (range: 5-145 months). In all T stages, the median was not reached for survival analysis. Five-year disease-specific survival for T1a, T1b, and T2 were 100%, 94.1%, and 97.1%, respectively. Five-year disease-free survival for T1a, T1b, and T2 were 100%, 87.0%, and 91.8%, respectively. CONCLUSION: Our results suggest that the current operative protocol can be applied to minimal invasive operations for GBC with similar oncologic outcomes as open approach. For T1/T2 GBC, radical cholecystectomy, including para-aortic lymph node dissection, can be performed safely with favorable oncologic outcomes.","Source":"PubMed","category":"HUMAN","training_data":"Oncologic Outcomes of Extended Lymphadenectomy without Liver Resection for T1/T2 Gallbladder Cancer PURPOSE: This study provides a standardized operative strategical algorithm that can be applied to patients with T1/T2 gallbladder cancer (GBC). Our aim was to determine the oncologic outcome of radical cholecystectomy with para-aortic lymph node dissection without liver resection in T1/T2 GBC. MATERIALS AND METHODS: From January 2005 to December 2017, 164 patients with GBC underwent operations by a single surgeon at Severance Hospital. A retrospective review was performed for 113 of these patients, who were pathologically determined to be in stages T1 and T2 according to American Joint Committee on Cancer 7th guidelines. RESULTS: Of the 113 patients, 109 underwent curative resection for T1/T2 GBC; four patients who underwent palliative operations without radical cholecystectomies were excluded from further analyses. For all T1b and T2 lesions, radical cholecystectomy with para-aortic lymph node dissection was performed without liver resection. There were four GBC-related mortalities, and 5-year disease-specific survival was 97.0%. The median follow-up was 50 months (range: 5-145 months). In all T stages, the median was not reached for survival analysis. Five-year disease-specific survival for T1a, T1b, and T2 were 100%, 94.1%, and 97.1%, respectively. Five-year disease-free survival for T1a, T1b, and T2 were 100%, 87.0%, and 91.8%, respectively. CONCLUSION: Our results suggest that the current operative protocol can be applied to minimal invasive operations for GBC with similar oncologic outcomes as open approach. For T1/T2 GBC, radical cholecystectomy, including para-aortic lymph node dissection, can be performed safely with favorable oncologic outcomes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"differentiation gallbladder cancer acute cholecystitis considerations surgeons emergency cholecystectomy cohort study purpose gallbladder cancer gbca uncommon malignancy vague non specific symptoms gbca sometimes diagnosed emergency cholecystectomy acute cholecystitis investigated differential diagnosis gbca acute cholecystitis materials methods thirteen patients diagnosed gbca emergency cholecystectomy carried acute cholecystitis radiologist blinded final diagnoses retrospectively reviewed computed tomography ct scans patients gbca 25 patients acute cholecystitis retrospectively reviewed medical records patients compared clinical characteristics ct findings patients gbca acute cholecystitis also investigated prognostic factors patients gbca underwent emergency cholecystectomy results gallbladder gb stones found often patients acute cholecystitis n 17 68 patients gbca n 7 53 8 p 0 486 patients gbca showed typical gb masses focal enhanced wall thickening compared diffuse wall thickening patients acute cholecystitis gbca patients showed irregular mural thickening gb enhancement differentiating carcinoma acute cholecystitis might sometimes possible latter group patients significantly lower c reactive protein crp levels p 0 033 less regional fat stranding p 0 047 survival significantly affected aggressive tumor characteristics lymphatic invasion p 0 025 depth tumor invasion p 0 004 r0 resection p 0 013 rather bile spillage p 0 112 conclusions surgeons deciding emergency cholecystectomy elderly patients acute cholecystitis must suspect gbca patients low crp level irregular mural thickening enhancement gb without regional fat stranding pubmed","probabilities":0.9799733,"Title":"Differentiation between gallbladder cancer with acute cholecystitis: Considerations for surgeons during emergency cholecystectomy, a cohort study","Abstract":"PURPOSE: Gallbladder cancer (GBCA) is an uncommon malignancy with vague and non-specific symptoms. GBCA is sometimes diagnosed after emergency cholecystectomy for acute cholecystitis. We investigated the differential diagnosis between GBCA with acute cholecystitis. MATERIALS AND METHODS: Thirteen patients were diagnosed with GBCA after emergency cholecystectomy carried out for acute cholecystitis. A radiologist who was blinded to the final diagnoses retrospectively reviewed the computed tomography (CT) scans of the patients with GBCA and 25 patients with acute cholecystitis. We retrospectively reviewed the medical records of these patients and compared the clinical characteristics and CT findings between patients with GBCA and those with acute cholecystitis. We also investigated the prognostic factors in patients with GBCA who underwent emergency cholecystectomy. RESULTS: Gallbladder (GB) stones were found more often in patients with acute cholecystitis (n = 17, 68%) than in patients with GBCA (n = 7, 53.8%) (p = 0.486). Patients with GBCA showed typical GB masses or focal enhanced wall thickening when compared to diffuse wall thickening in patients with acute cholecystitis. Some GBCA patients showed irregular mural thickening and GB enhancement. Differentiating carcinoma from acute cholecystitis might sometimes not possible, but the latter group of patients had significantly lower C-reactive protein (CRP) levels (p = 0.033) and less regional fat stranding (p = 0.047). Survival was significantly affected by aggressive tumor characteristics (lymphatic invasion [p = 0.025], depth of tumor invasion [p = 0.004]) or R0 resection (p = 0.013) rather than bile spillage (p = 0.112). CONCLUSIONS: Surgeons deciding on emergency cholecystectomy for elderly patients with acute cholecystitis must suspect GBCA in patients with a low CRP level, irregular mural thickening or enhancement of GB without regional fat stranding.","Source":"PubMed","category":"HUMAN","training_data":"Differentiation between gallbladder cancer with acute cholecystitis: Considerations for surgeons during emergency cholecystectomy, a cohort study PURPOSE: Gallbladder cancer (GBCA) is an uncommon malignancy with vague and non-specific symptoms. GBCA is sometimes diagnosed after emergency cholecystectomy for acute cholecystitis. We investigated the differential diagnosis between GBCA with acute cholecystitis. MATERIALS AND METHODS: Thirteen patients were diagnosed with GBCA after emergency cholecystectomy carried out for acute cholecystitis. A radiologist who was blinded to the final diagnoses retrospectively reviewed the computed tomography (CT) scans of the patients with GBCA and 25 patients with acute cholecystitis. We retrospectively reviewed the medical records of these patients and compared the clinical characteristics and CT findings between patients with GBCA and those with acute cholecystitis. We also investigated the prognostic factors in patients with GBCA who underwent emergency cholecystectomy. RESULTS: Gallbladder (GB) stones were found more often in patients with acute cholecystitis (n = 17, 68%) than in patients with GBCA (n = 7, 53.8%) (p = 0.486). Patients with GBCA showed typical GB masses or focal enhanced wall thickening when compared to diffuse wall thickening in patients with acute cholecystitis. Some GBCA patients showed irregular mural thickening and GB enhancement. Differentiating carcinoma from acute cholecystitis might sometimes not possible, but the latter group of patients had significantly lower C-reactive protein (CRP) levels (p = 0.033) and less regional fat stranding (p = 0.047). Survival was significantly affected by aggressive tumor characteristics (lymphatic invasion [p = 0.025], depth of tumor invasion [p = 0.004]) or R0 resection (p = 0.013) rather than bile spillage (p = 0.112). CONCLUSIONS: Surgeons deciding on emergency cholecystectomy for elderly patients with acute cholecystitis must suspect GBCA in patients with a low CRP level, irregular mural thickening or enhancement of GB without regional fat stranding. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact specialized multi disciplinary approach integrated pathway outcomes hilar cholangiocarcinoma aims assess outcomes patients hilar cholangiocarcinoma following referral specialist multi disciplinary team methods 11 year period patients referred hilar cholangiocarcinoma identified prospectively maintained registry collated data included demographics operative findings histo pathological data survival differences prognostic factors determined results 345 patients referred hilar cholangiocarcinoma 57 16 5 patients surgery prior 2008 143 patients referred 17 11 9 patients underwent surgery compared 40 19 8 202 patients referred 2008 onwards p 0 051 surgery group majority patients underwent left hemi hepatectomy n 19 addition portal vein n 5 hepatic artery n 2 inferior vena cava n 3 resections performed r0 resection rate 73 7 morbidity mortality rates 59 6 14 0 respectively median disease free survival 16 4 101 months presence lymph node metastasis p 0 002 predictor poorer disease free survival 5 year overall survival 39 5 significantly better palliative group p 0 001 conclusions surgery optimal treatment option patients hilar cholangiocarcinoma associated better overall survival prompt referral tertiary centres core team clinicians manage difficult condition may allow patients come potentially curative surgical resections pubmed","probabilities":0.9799733,"Title":"Impact of specialized multi-disciplinary approach and an integrated pathway on outcomes in hilar cholangiocarcinoma","Abstract":"AIMS: To assess the outcomes of patients with hilar cholangiocarcinoma following referral to a specialist multi-disciplinary team. METHODS: Over an 11-year period, patients referred with hilar cholangiocarcinoma were identified from a prospectively maintained registry. Collated data included demographics, operative findings and histo-pathological data. Survival differences and prognostic factors were determined. RESULTS: 345 patients were referred with hilar cholangiocarcinoma, of which 57 (16.5%) patients had surgery. Prior to 2008, of 143 patients referred, only 17 (11.9%) patients underwent surgery, compared to 40 (19.8%) of 202 patients referred from 2008 onwards (p = 0.051). In the surgery group, the majority of patients underwent left hemi-hepatectomy (n = 19). In addition, portal vein (n = 5), hepatic artery (n = 2) and inferior vena cava (n = 3) resections were performed. The R0 resection rate was 73.7%. The morbidity and mortality rates were 59.6% and 14.0%, respectively. The median disease-free survival was 16 (4-101) months. The presence of lymph node metastasis (p = 0.002) was the only predictor of poorer disease-free survival. The 5-year overall survival was 39.5% and was significantly better than that of the palliative group (p < 0.001). CONCLUSIONS: Surgery is the optimal treatment option for patients with hilar cholangiocarcinoma and is associated with better overall survival. Prompt referral to tertiary centres with a core team of clinicians to manage this difficult condition may allow more patients to come to potentially curative surgical resections.","Source":"PubMed","category":"HUMAN","training_data":"Impact of specialized multi-disciplinary approach and an integrated pathway on outcomes in hilar cholangiocarcinoma AIMS: To assess the outcomes of patients with hilar cholangiocarcinoma following referral to a specialist multi-disciplinary team. METHODS: Over an 11-year period, patients referred with hilar cholangiocarcinoma were identified from a prospectively maintained registry. Collated data included demographics, operative findings and histo-pathological data. Survival differences and prognostic factors were determined. RESULTS: 345 patients were referred with hilar cholangiocarcinoma, of which 57 (16.5%) patients had surgery. Prior to 2008, of 143 patients referred, only 17 (11.9%) patients underwent surgery, compared to 40 (19.8%) of 202 patients referred from 2008 onwards (p = 0.051). In the surgery group, the majority of patients underwent left hemi-hepatectomy (n = 19). In addition, portal vein (n = 5), hepatic artery (n = 2) and inferior vena cava (n = 3) resections were performed. The R0 resection rate was 73.7%. The morbidity and mortality rates were 59.6% and 14.0%, respectively. The median disease-free survival was 16 (4-101) months. The presence of lymph node metastasis (p = 0.002) was the only predictor of poorer disease-free survival. The 5-year overall survival was 39.5% and was significantly better than that of the palliative group (p < 0.001). CONCLUSIONS: Surgery is the optimal treatment option for patients with hilar cholangiocarcinoma and is associated with better overall survival. Prompt referral to tertiary centres with a core team of clinicians to manage this difficult condition may allow more patients to come to potentially curative surgical resections. PubMed","prediction_labels":"HUMAN"},{"cleaned":"sex specific race ethnicity specific disparities cholangiocarcinoma incidence prevalence usa updated analysis 2000 2011 surveillance epidemiology end results registry aim cholangiocarcinoma cca uncommon lethal malignancy increasing worldwide incidence intrahepatic cholangiocarcinoma icc decreasing incidence extrahepatic cholangiocarcinoma ecc evaluate age specific sex specific race ethnicity specific variations cca incidence usa methods using population based cancer registry data 2000 2011 surveillance epidemiology end results registry retrospectively evaluated age specific sex specific race ethnicity specific variations incidence prevalence cca stratified icc ecc subtypes among adults usa results total 11 296 patients icc 8672 patients ecc identified icc incidence significantly higher ecc incidence 1 6 vs 1 3 per 100 000 year p 0 01 among race ethnic groups among icc ecc asians highest cancer incidence stratified age cca incidence increased age among groups however rising incidence rapid among asians example among patients aged 80 years incidence icc among asians nearly twice incidence among non hispanic whites 13 8 vs 7 2 per 100 000 year overall cca incidence higher among men compared women increasing age sex specific disparity pronounced example among patients aged 80 years incidence icc 9 8 per 100 000 year among men 6 9 per 100 000 year among women conclusion among adults cca usa increasing age associated increasing incidence cca addition sex specific race ethnicity specific disparities seen highest incidence cca among men among asians stn","probabilities":0.9799733,"Title":"Sex-Specific And Race/Ethnicity-Specific Disparities In Cholangiocarcinoma Incidence And Prevalence In The Usa: An Updated Analysis Of The 2000-2011 Surveillance Epidemiology And End Results Registry","Abstract":"Aim: Cholangiocarcinoma (CCA) is an uncommon but lethal malignancy with an increasing worldwide incidence of intrahepatic cholangiocarcinoma (ICC), but decreasing incidence of extrahepatic cholangiocarcinoma (ECC). To evaluate age-specific, sex-specific, race/ethnicity-specific variations in CCA incidence in the USA. \r\n\r\n Methods: Using population-based cancer registry data from the 2000-2011 Surveillance, Epidemiology and End Results registry, we retrospectively evaluated age-specific, sex-specific, race/ethnicity-specific variations in incidence and prevalence of CCA stratified by ICC and ECC subtypes among adults in the USA. \r\n\r\n Results: A total of 11 296 patients with ICC and 8672 patients with ECC were identified. ICC incidence was significantly higher than ECC incidence (1.6 vs 1.3 per 100 000/year, P < 0.01). Among all race/ethnic groups and among both ICC and ECC, Asians had the highest cancer incidence. When stratified by age, CCA incidence increased with age among all groups; however, the rising incidence was most rapid among Asians. For example, among patients aged 80 years and over, the incidence of ICC among Asians was nearly twice the incidence among non-Hispanic whites (13.8 vs 7.2 per 100 000/year). Overall, CCA incidence was higher among men compared with women, and with increasing age, this sex-specific disparity was more pronounced. For example, among patients aged 80 years and over, the incidence of ICC was 9.8 per 100 000/year among men and 6.9 per 100 000/year among women. \r\n\r\n Conclusion: Among adults with CCA in the USA, increasing age was associated with increasing incidence of CCA. In addition, sex-specific and race/ethnicity-specific disparities were seen with the highest incidence of CCA among men and among Asians.","Source":"STN","category":"HUMAN","training_data":"Sex-Specific And Race/Ethnicity-Specific Disparities In Cholangiocarcinoma Incidence And Prevalence In The Usa: An Updated Analysis Of The 2000-2011 Surveillance Epidemiology And End Results Registry Aim: Cholangiocarcinoma (CCA) is an uncommon but lethal malignancy with an increasing worldwide incidence of intrahepatic cholangiocarcinoma (ICC), but decreasing incidence of extrahepatic cholangiocarcinoma (ECC). To evaluate age-specific, sex-specific, race/ethnicity-specific variations in CCA incidence in the USA. \r\n\r\n Methods: Using population-based cancer registry data from the 2000-2011 Surveillance, Epidemiology and End Results registry, we retrospectively evaluated age-specific, sex-specific, race/ethnicity-specific variations in incidence and prevalence of CCA stratified by ICC and ECC subtypes among adults in the USA. \r\n\r\n Results: A total of 11 296 patients with ICC and 8672 patients with ECC were identified. ICC incidence was significantly higher than ECC incidence (1.6 vs 1.3 per 100 000/year, P < 0.01). Among all race/ethnic groups and among both ICC and ECC, Asians had the highest cancer incidence. When stratified by age, CCA incidence increased with age among all groups; however, the rising incidence was most rapid among Asians. For example, among patients aged 80 years and over, the incidence of ICC among Asians was nearly twice the incidence among non-Hispanic whites (13.8 vs 7.2 per 100 000/year). Overall, CCA incidence was higher among men compared with women, and with increasing age, this sex-specific disparity was more pronounced. For example, among patients aged 80 years and over, the incidence of ICC was 9.8 per 100 000/year among men and 6.9 per 100 000/year among women. \r\n\r\n Conclusion: Among adults with CCA in the USA, increasing age was associated with increasing incidence of CCA. In addition, sex-specific and race/ethnicity-specific disparities were seen with the highest incidence of CCA among men and among Asians. STN","prediction_labels":"HUMAN"},{"cleaned":"combined pancreatoduodenectomy advanced gallbladder cancer justified background clinical impact combined pancreatoduodenectomy pd advanced gallbladder cancer remains unclear methods total 96 patients underwent resection stage ii iii iv gallbladder cancer enrolled patients lower bile duct involvement pancreatic duodenal infiltration peripancreatic lymph node metastasis considered candidates combined pd operative outcomes compared patients treated pd pd group n 21 treated without pd non pd group n 75 treated major hepatopancreatoduodenectomy major hpd group n 9 treated major hepatectomy major hepatectomy group n 20 results overall morbidity pd group greater non pd group 81 vs 23 p 001 whereas overall survival os comparable groups 5 year os 39 8 vs 46 7 p 96 hospital mortality pd group serum albumin 3 0 g dl p 004 tumor size 9 0 cm p 029 associated independently poor prognosis pd group overall morbidity major hpd group greater major hepatectomy group 89 vs 40 p 014 whereas os comparable groups 5 year os 34 6 vs 21 1 p 57 os major hpd group better unresectable group n 18 p 017 conclusion combined pd including major hpd beneficial selected patients advanced gallbladder cancer however indications carefully evaluated greater morbidity rates pubmed","probabilities":0.9799733,"Title":"Is combined pancreatoduodenectomy for advanced gallbladder cancer justified?","Abstract":"BACKGROUND: The clinical impact of combined pancreatoduodenectomy (PD) for advanced gallbladder cancer remains unclear. METHODS: A total of 96 patients who underwent resection for stage II, III, or IV gallbladder cancer were enrolled. Patients with lower bile duct involvement, pancreatic or duodenal infiltration, or peripancreatic lymph node metastasis were considered candidates for combined PD. The operative outcomes were compared between the patients treated with PD (PD group, n = 21) and those treated without PD (non-PD group, n = 75), and between those treated with major hepatopancreatoduodenectomy (major HPD group, n = 9) and those treated with major hepatectomy (major hepatectomy group, n = 20). RESULTS: Overall morbidity in the PD group was greater than that in the non-PD group (81% vs 23%, P < .001), whereas the overall survival (OS) was comparable between the groups (5-year OS; 39.8% vs 46.7%, P = .96). There was no in-hospital mortality in the PD group. A serum albumin <3.0 g/dL (P = .004) and tumor size ≥ 9.0 cm (P = .029) were associated independently with a poor prognosis in the PD group. Overall morbidity in the major HPD group was greater than that in the major hepatectomy group (89% vs 40%, P = .014), whereas the OS was comparable between the groups (5-year OS; 34.6% vs 21.1%, P = .57), and the OS of major HPD group was better than that of unresectable group (n = 18, P = .017). CONCLUSION: Combined PD, including major HPD, is beneficial for selected patients of advanced gallbladder cancer; however, the indications should be carefully evaluated because of greater morbidity rates.","Source":"PubMed","category":"HUMAN","training_data":"Is combined pancreatoduodenectomy for advanced gallbladder cancer justified? BACKGROUND: The clinical impact of combined pancreatoduodenectomy (PD) for advanced gallbladder cancer remains unclear. METHODS: A total of 96 patients who underwent resection for stage II, III, or IV gallbladder cancer were enrolled. Patients with lower bile duct involvement, pancreatic or duodenal infiltration, or peripancreatic lymph node metastasis were considered candidates for combined PD. The operative outcomes were compared between the patients treated with PD (PD group, n = 21) and those treated without PD (non-PD group, n = 75), and between those treated with major hepatopancreatoduodenectomy (major HPD group, n = 9) and those treated with major hepatectomy (major hepatectomy group, n = 20). RESULTS: Overall morbidity in the PD group was greater than that in the non-PD group (81% vs 23%, P < .001), whereas the overall survival (OS) was comparable between the groups (5-year OS; 39.8% vs 46.7%, P = .96). There was no in-hospital mortality in the PD group. A serum albumin <3.0 g/dL (P = .004) and tumor size ≥ 9.0 cm (P = .029) were associated independently with a poor prognosis in the PD group. Overall morbidity in the major HPD group was greater than that in the major hepatectomy group (89% vs 40%, P = .014), whereas the OS was comparable between the groups (5-year OS; 34.6% vs 21.1%, P = .57), and the OS of major HPD group was better than that of unresectable group (n = 18, P = .017). CONCLUSION: Combined PD, including major HPD, is beneficial for selected patients of advanced gallbladder cancer; however, the indications should be carefully evaluated because of greater morbidity rates. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival patterns gallbladder cancer recent decades experience national cancer institute introduction gallbladder cancer five year survival rate 5 amenable surgery even patients undergoing radical surgical resection median survival 35 stages study aim highlight survival improvement changing neoadjuvant adjuvant regimens last 20 years methods patients gallbladder cancer reviewed tumor registry 1990 2008 stages assigned ajcc 6th edition survival curves compared split period 1990 2000 2000 2008 results 94 patients gallbladder cancer analyzed 42 patients stratified 1990 2000 52 patients 2000 2008 average age decades significant 64vs59 p ns 91 patents underwent surgery n 83 51 group laparoscopic cholecystectomy n 43 13 open cholecystectomy n 11 initial surgery 76 group laparoscopic cholecystectomy necessitated operative intervention n 33 36 staged three greater n 12 p 0 05 laparoscopic cholecystectomy group 23 presented port site metastasis definitive surgery n 10 48 underwent bisubsegemental resection portal lymphadenectomy n 40 15 common bile duct resection added liver bed resection n 13 7 necessitated enbloc colectomy intraoperative recognized t4 disease n 6 30 bile duct resection procedure earlier decade n 4 p 0 14 survival difference noted subset patients decades significance noted stage separation two decades p 0 988 majority patients n 20 vs 26 stage 4 kaplan meier calculated survival curves note stage differences respective decades conclusion change noted survival stage despite shifting adjuvant neoadjuvant paradigm laparoscopic cholecystectomy identification incidental gallbladder carcinoma increased dramatically despite gallbladder cancer discovered incidentally prognosis varies extended resection often necessary google scholar","probabilities":0.9799733,"Title":"Survival Patterns For Gallbladder Cancer In Recent Decades; Experience At A National Cancer Institute","Abstract":"Introduction:Gallbladder cancer has a five year survival rate of <5% for those not amenable\nto surgery. Even patients undergoing radical surgical resection, the median survival is 35%\nfor all stages. The study's aim was to highlight any survival improvement with changing\nneoadjuvant/adjuvant regimens over the last 20 years Methods:Patients with Gallbladder\ncancer were reviewed from our tumor registry between 1990-2008. Stages were assigned\nby AJCC 6th edition; survival curves were compared over a split period from 1990-2000\n& 2000-2008. Results:94 patients with gallbladder cancer were analyzed.42 patients were\nstratified 1990-2000, and 52 patients from 2000-2008. Average age between the decades\nwas not significant. (64vs59, P=NS) 91% of the patents underwent surgery(n=83). 51% of\nthat group had laparoscopic cholecystectomy(n=43) and 13% had an open cholecystectomy(n=11) as initial surgery . 76% of the group having laparoscopic cholecystectomy necessitated further operative intervention(n=33), with 36% being staged three or greater(n=12)\n(p<0.05). Of the laparoscopic cholecystectomy group, 23% presented with port site metastasis\nat definitive surgery(n=10). 48% underwent bisubsegemental resection and portal lymphadenectomy(n=40). 15% had a common bile duct resection added to their liver bed resection(n=\n13) and 7% necessitated enbloc colectomy for intraoperative recognized T4 disease(n=6).\n30% of those who had their bile duct resection had their procedure in the earlier decade\n(n=4,p< 0.14); no survival difference noted in this subset of patients between decades. No\nsignificance was noted in stage separation of the two decades (P<0.988). Majority of the\npatients (n=20 vs 26) were stage 4. Kaplan Meier calculated survival curves note no stage\ndifferences between the respective decades. Conclusion: No change is noted in survival\nby stage despite shifting from an adjuvant to neoadjuvant paradigm. With laparoscopic\ncholecystectomy, the identification of incidental gallbladder carcinoma has increased dramatically. Despite gallbladder cancer being discovered incidentally prognosis varies and extended\nresection is often necessary.","Source":"Google Scholar","category":"HUMAN","training_data":"Survival Patterns For Gallbladder Cancer In Recent Decades; Experience At A National Cancer Institute Introduction:Gallbladder cancer has a five year survival rate of <5% for those not amenable\nto surgery. Even patients undergoing radical surgical resection, the median survival is 35%\nfor all stages. The study's aim was to highlight any survival improvement with changing\nneoadjuvant/adjuvant regimens over the last 20 years Methods:Patients with Gallbladder\ncancer were reviewed from our tumor registry between 1990-2008. Stages were assigned\nby AJCC 6th edition; survival curves were compared over a split period from 1990-2000\n& 2000-2008. Results:94 patients with gallbladder cancer were analyzed.42 patients were\nstratified 1990-2000, and 52 patients from 2000-2008. Average age between the decades\nwas not significant. (64vs59, P=NS) 91% of the patents underwent surgery(n=83). 51% of\nthat group had laparoscopic cholecystectomy(n=43) and 13% had an open cholecystectomy(n=11) as initial surgery . 76% of the group having laparoscopic cholecystectomy necessitated further operative intervention(n=33), with 36% being staged three or greater(n=12)\n(p<0.05). Of the laparoscopic cholecystectomy group, 23% presented with port site metastasis\nat definitive surgery(n=10). 48% underwent bisubsegemental resection and portal lymphadenectomy(n=40). 15% had a common bile duct resection added to their liver bed resection(n=\n13) and 7% necessitated enbloc colectomy for intraoperative recognized T4 disease(n=6).\n30% of those who had their bile duct resection had their procedure in the earlier decade\n(n=4,p< 0.14); no survival difference noted in this subset of patients between decades. No\nsignificance was noted in stage separation of the two decades (P<0.988). Majority of the\npatients (n=20 vs 26) were stage 4. Kaplan Meier calculated survival curves note no stage\ndifferences between the respective decades. Conclusion: No change is noted in survival\nby stage despite shifting from an adjuvant to neoadjuvant paradigm. With laparoscopic\ncholecystectomy, the identification of incidental gallbladder carcinoma has increased dramatically. Despite gallbladder cancer being discovered incidentally prognosis varies and extended\nresection is often necessary. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"inflammatory bowel disease increase risk malignancies patients primary sclerosing cholangitis systematic review meta analysis introduction primary sclerosing cholangitis carries increased risk malignancies including cholangiocarcinoma cca colorectal cancer crc strong association psc inflammatory bowel disease ibd shown studies revealed increased risk malignancies liver transplantation ibd overlaps psc however data scarce conflicting study aimed perform meta analysis existing clinical trials evaluate ibd yields increased risk malignancies patients psc methods systematic search pubmed scopus cinahl cochrane database systematic reviews conducted april 2016 two independent reviewers h d identified trials evaluated risk developing cca crc malignancies patients psc ibd versus psc alone primary outcome risk cca secondary outcomes included risk crc hepatocellular carcinoma gallbladder extra biliary cancers liver transplantation mortality review manager 5 3 software program used statistical analysis results seven studies met inclusion criteria total 1 205 patients included metaanalysis significant differences found psc patients without associated ibd terms cholangiocarcinoma gall bladder cancer hepatocellular carcinoma liver transplantation death rates incidence colorectal cancer higher group associated ibd mean odds ratio 6 16 p 0 001 95 ci 2 31 16 42 conclusion association psc ibd didn seem increase risk cholangiocarcinoma gall bladder cancer hepatocellular carcinoma compared patients psc alone increased risk colorectal cancer likely related presence ibd google scholar","probabilities":0.9799733,"Title":"Does Inflammatory Bowel Disease Increase The Risk Of Malignancies In Patients With Primary Sclerosing Cholangitis: A Systematic Review And Meta-Analysis","Abstract":"Introduction: Primary sclerosing cholangitis carries an increased risk of malignancies including cholangiocarcinoma (CCA), and colorectal cancer (CRC). A strong association between PSC and inflammatory bowel disease (IBD) has been shown, and studies revealed an increased risk of malignancies and liver transplantation when IBD overlaps PSC, however data about it is scarce and conflicting. In our study we aimed to perform a meta-analysis of existing clinical trials to evaluate if IBD yields an increased risk of malignancies in patients with PSC.\nMethods: A systematic search of PubMed, Scopus, CINAHL, and Cochrane database of systematic reviews was conducted in April/2016. Two independent reviewers (S.H and D.A) identified trials that evaluated the risk of developing CCA, CRC, and other malignancies in patients with PSC and IBD versus PSC alone. The primary outcome was the risk of CCA, and secondary outcomes included risk of CRC, hepatocellular carcinoma, gallbladder and extra-biliary cancers, liver transplantation and mortality. Review Manager 5.3 software program was used for statistical analysis.\nResults: Seven studies met the inclusion criteria. A total of 1,205 patients were included in the metaanalysis. No significant differences were found between PSC patients with and without associated IBD in terms of cholangiocarcinoma, gall bladder cancer, hepatocellular carcinoma, liver transplantation, and death rates. The incidence of colorectal cancer was higher in the group with associated IBD, with a mean odds ratio of 6.16, P < 0.001 (95% CI: 2.31-16.42).\nConclusion: The association between PSC and IBD didn't seem to increase the risk of cholangiocarcinoma, gall bladder cancer or hepatocellular carcinoma when compared to patients with PSC alone. The increased risk of colorectal cancer is likely related to the presence of IBD.","Source":"Google Scholar","category":"HUMAN","training_data":"Does Inflammatory Bowel Disease Increase The Risk Of Malignancies In Patients With Primary Sclerosing Cholangitis: A Systematic Review And Meta-Analysis Introduction: Primary sclerosing cholangitis carries an increased risk of malignancies including cholangiocarcinoma (CCA), and colorectal cancer (CRC). A strong association between PSC and inflammatory bowel disease (IBD) has been shown, and studies revealed an increased risk of malignancies and liver transplantation when IBD overlaps PSC, however data about it is scarce and conflicting. In our study we aimed to perform a meta-analysis of existing clinical trials to evaluate if IBD yields an increased risk of malignancies in patients with PSC.\nMethods: A systematic search of PubMed, Scopus, CINAHL, and Cochrane database of systematic reviews was conducted in April/2016. Two independent reviewers (S.H and D.A) identified trials that evaluated the risk of developing CCA, CRC, and other malignancies in patients with PSC and IBD versus PSC alone. The primary outcome was the risk of CCA, and secondary outcomes included risk of CRC, hepatocellular carcinoma, gallbladder and extra-biliary cancers, liver transplantation and mortality. Review Manager 5.3 software program was used for statistical analysis.\nResults: Seven studies met the inclusion criteria. A total of 1,205 patients were included in the metaanalysis. No significant differences were found between PSC patients with and without associated IBD in terms of cholangiocarcinoma, gall bladder cancer, hepatocellular carcinoma, liver transplantation, and death rates. The incidence of colorectal cancer was higher in the group with associated IBD, with a mean odds ratio of 6.16, P < 0.001 (95% CI: 2.31-16.42).\nConclusion: The association between PSC and IBD didn't seem to increase the risk of cholangiocarcinoma, gall bladder cancer or hepatocellular carcinoma when compared to patients with PSC alone. The increased risk of colorectal cancer is likely related to the presence of IBD. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"incidence rates liver cancer peaked united states background liver cancer incidence increased several decades united states recently reports suggested rates hepatocellular carcinoma hcc dominant form liver cancer declined certain groups however authors knowledge recent histology specific liver cancer rates reported date methods authors examined incidence hcc intrahepatic cholangiocarcinoma icc 1992 2016 using data surveillance epidemiology end results registries age standardized incidence rates calculated histology sex race ethnicity age trends analyzed using national cancer institute joinpoint regression program estimate annual percent change results 2011 2016 hcc rates significantly declined annual percent change 1 9 prominent declines noted among males asian pacific islanders individuals aged 50 years conversely icc rates increased 2002 2016 conclusions declining hcc rates may persist due improved treatment hepatitis c virus competing causes mortality among individuals fatty liver disease google scholar","probabilities":0.9799733,"Title":"Have Incidence Rates Of Liver Cancer Peaked In The United States?","Abstract":"Background\nLiver cancer incidence has increased for several decades in the United States. Recently, reports have suggested that rates of hepatocellular carcinoma (HCC), the dominant form of liver cancer, had declined in certain groups. However, to the authors' knowledge, the most recent histology‐specific liver cancer rates have not been reported to date.\nMethods\nThe authors examined the incidence of HCC and intrahepatic cholangiocarcinoma (ICC) from 1992 through 2016 using data from the Surveillance, Epidemiology, and End Results registries. Age‐standardized incidence rates were calculated by histology, sex, race and/or ethnicity, and age. Trends were analyzed using the National Cancer Institute's Joinpoint Regression Program to estimate the annual percent change.\nResults\nBetween 2011 and 2016, HCC rates significantly declined (annual percent change, −1.9%), with more prominent declines noted among males, Asian/Pacific Islanders, and individuals aged <50 years. Conversely, ICC rates increased from 2002 through 2016.\nConclusions\nDeclining HCC rates may persist due to improved treatment of the hepatitis C virus and/or competing causes of mortality among individuals with fatty liver disease.","Source":"Google Scholar","category":"HUMAN","training_data":"Have Incidence Rates Of Liver Cancer Peaked In The United States? Background\nLiver cancer incidence has increased for several decades in the United States. Recently, reports have suggested that rates of hepatocellular carcinoma (HCC), the dominant form of liver cancer, had declined in certain groups. However, to the authors' knowledge, the most recent histology‐specific liver cancer rates have not been reported to date.\nMethods\nThe authors examined the incidence of HCC and intrahepatic cholangiocarcinoma (ICC) from 1992 through 2016 using data from the Surveillance, Epidemiology, and End Results registries. Age‐standardized incidence rates were calculated by histology, sex, race and/or ethnicity, and age. Trends were analyzed using the National Cancer Institute's Joinpoint Regression Program to estimate the annual percent change.\nResults\nBetween 2011 and 2016, HCC rates significantly declined (annual percent change, −1.9%), with more prominent declines noted among males, Asian/Pacific Islanders, and individuals aged <50 years. Conversely, ICC rates increased from 2002 through 2016.\nConclusions\nDeclining HCC rates may persist due to improved treatment of the hepatitis C virus and/or competing causes of mortality among individuals with fatty liver disease. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic value site specific metastases patients advanced intrahepatic cholangiocarcinoma seer database analysis intrahepatic cholangiocarcinoma icc aggressive malignancy poor prognosis increasing incidence due asymptomatic manifestation icc often progresses metastatic stage diagnosis current study attempted evaluate prognostic value site specific metastases patients metastatic icc surveillance epidemiology end results seer database 2010 2015 queried metastatic icc patients classified according metastatic sites kaplan meier analysis used survival comparisons multivariate analysis performed elicit characteristics independently associated survival total 1567 patients identified included analysis compared multiple site metastases patients single site metastases better prognostic outcomes among single site metastases regional lymph nodes metastases best prognosis liver metastases better prognostic outcomes bone metastases significant difference found lung bone liver metastasis local treatment primary tumor might benefit patients isolated lymph nodes metastases exceptional cases patients liver metastases different metastatic sites distinct impact survival outcomes patients advanced icc highly selected subset might benefit local treatment primary tumor pubmed","probabilities":0.9799733,"Title":"Prognostic value of site-specific metastases for patients with advanced intrahepatic cholangiocarcinoma: A SEER database analysis","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis and increasing incidence. Due to its asymptomatic manifestation, ICC often progresses to a metastatic stage on diagnosis. The current study attempted to evaluate the prognostic value of site-specific metastases in patients with metastatic ICC.Surveillance, Epidemiology, and End Results (SEER) database (2010-2015) was queried and metastatic ICC patients were classified according to the metastatic sites. Kaplan-Meier analysis was used for survival comparisons and multivariate analysis was performed to elicit characteristics independently associated with survival.A total of 1567 patients were identified and included in the analysis. Compared with those with multiple-site metastases, patients with single-site metastases had better prognostic outcomes. Among the single-site metastases, regional lymph nodes metastases had the best prognosis; liver metastases had better prognostic outcomes than bone metastases; no significant difference was found between lung and bone or liver metastasis. Local treatment of primary tumor might benefit patients with isolated lymph nodes metastases and few exceptional cases of patients with liver metastases.Different metastatic sites have distinct impact on the survival outcomes of patients with advanced ICC and highly selected subset of them might benefit from the local treatment of the primary tumor.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic value of site-specific metastases for patients with advanced intrahepatic cholangiocarcinoma: A SEER database analysis Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy with poor prognosis and increasing incidence. Due to its asymptomatic manifestation, ICC often progresses to a metastatic stage on diagnosis. The current study attempted to evaluate the prognostic value of site-specific metastases in patients with metastatic ICC.Surveillance, Epidemiology, and End Results (SEER) database (2010-2015) was queried and metastatic ICC patients were classified according to the metastatic sites. Kaplan-Meier analysis was used for survival comparisons and multivariate analysis was performed to elicit characteristics independently associated with survival.A total of 1567 patients were identified and included in the analysis. Compared with those with multiple-site metastases, patients with single-site metastases had better prognostic outcomes. Among the single-site metastases, regional lymph nodes metastases had the best prognosis; liver metastases had better prognostic outcomes than bone metastases; no significant difference was found between lung and bone or liver metastasis. Local treatment of primary tumor might benefit patients with isolated lymph nodes metastases and few exceptional cases of patients with liver metastases.Different metastatic sites have distinct impact on the survival outcomes of patients with advanced ICC and highly selected subset of them might benefit from the local treatment of the primary tumor. PubMed","prediction_labels":"HUMAN"},{"cleaned":"statins associated reduced risk cholangiocarcinoma population based case control study aims cholangiocarcinoma cca second common primary liver cancer world due lack effective treatments survival rate cca low usually considered difficult diagnose early date effective strategies prevention cca developed statins cholesterol lowering agents possess pleiotropic properties use statins may reduce cancer risk aim study investigate effect statin use risk cca methods used nationwide insurance data perform case control study including 3174 cca patients diagnosed 2002 2011 3174 propensity score matched controls odds ratios ors 95 confidence intervals ci calculated assess association cca risk statin use type statin dose results patients cca slightly younger controls mean ages 67 4 sd 12 3 68 5 sd 13 2 years p 0 001 respectively less users statins 22 7 vs 26 5 p 0 001 overall adjusted statin use associated cca 0 80 95 ci 0 71 0 90 lowered longer medications ranged 0 65 0 77 stronger dose response association seen using lovastatin conclusions statin use associated reduced risk cca dose response relationship use statins risk cca pubmed","probabilities":0.9799733,"Title":"Statins are associated with a reduced risk of cholangiocarcinoma: a population-based case-control study","Abstract":"AIMS: Cholangiocarcinoma (CCA) is the second most common primary liver cancer in the world. Due to the lack of effective treatments, the survival rate of CCA is low and it is usually considered difficult to diagnose early. To date, no effective strategies for the prevention of CCA have been developed. Statins are cholesterol-lowering agents which possess pleiotropic properties and the use of statins may reduce cancer risk. The aim of the study was to investigate the effect of statin use on the risk of CCA. METHODS: We used nationwide insurance data to perform a case-control study including 3174 CCA patients diagnosed in 2002-2011 and 3174 propensity score matched controls. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated to assess the association between CCA risk and statin use by type of statin and dose. RESULTS: Patients with CCA were slightly younger than controls with mean ages of 67.4 (SD 12.3) and 68.5 (SD 13.2) years (P = 0.001), respectively, and had less users of statins (22.7 vs. 26.5%, P < 0.001). The overall adjusted OR of statin use associated CCA was 0.80 (95% CI 0.71, 0.90) and lowered for those with longer medications. The OR ranged from 0.65 to 0.77. Stronger dose-response association was seen when using lovastatin. CONCLUSIONS: Statin use is associated with reduced risk of CCA and there is a dose-response relationship between the use of statins and risk of CCA.","Source":"PubMed","category":"HUMAN","training_data":"Statins are associated with a reduced risk of cholangiocarcinoma: a population-based case-control study AIMS: Cholangiocarcinoma (CCA) is the second most common primary liver cancer in the world. Due to the lack of effective treatments, the survival rate of CCA is low and it is usually considered difficult to diagnose early. To date, no effective strategies for the prevention of CCA have been developed. Statins are cholesterol-lowering agents which possess pleiotropic properties and the use of statins may reduce cancer risk. The aim of the study was to investigate the effect of statin use on the risk of CCA. METHODS: We used nationwide insurance data to perform a case-control study including 3174 CCA patients diagnosed in 2002-2011 and 3174 propensity score matched controls. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated to assess the association between CCA risk and statin use by type of statin and dose. RESULTS: Patients with CCA were slightly younger than controls with mean ages of 67.4 (SD 12.3) and 68.5 (SD 13.2) years (P = 0.001), respectively, and had less users of statins (22.7 vs. 26.5%, P < 0.001). The overall adjusted OR of statin use associated CCA was 0.80 (95% CI 0.71, 0.90) and lowered for those with longer medications. The OR ranged from 0.65 to 0.77. Stronger dose-response association was seen when using lovastatin. CONCLUSIONS: Statin use is associated with reduced risk of CCA and there is a dose-response relationship between the use of statins and risk of CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression nek7 foxm1 plk1 gallbladder cancer relationships clinicopathologic features survival purpose gallbladder carcinoma gc generally considered relatively rare malignancy poor prognosis order guide clinicians selecting suitable treatment gc patients reliable markers predictive poor clinical outcome desirable study analyzed expression polo like kinase 1 plk1 nima related kinases 7 nek7 forkhead box m1 foxm1 gc tissues relationship clinicopathologic features survival methods immunohistochemically investigated 76 specimens gallbladder carcinoma pericarcinoma normal tissues using nek7 foxm1 plk1 antibodies analyzed overall survival time 76 patients results significant correlations high level expression nek7 foxm1 plk1 tumor differentiation nevin staging metastasis high level expression nek7 foxm1 plk1 significantly associated shorter overall survival time univariate analysis log rank test also identified independent prognostic factor multivariate analysis conclusion nek7 foxm1 plk1 significantly associated certain clinicopathologic indices gc evaluation nek7 foxm1 plk1 expression may important factor identifying group poor gc prognosis pubmed","probabilities":0.88235295,"Title":"The expression of Nek7, FoxM1, and Plk1 in gallbladder cancer and their relationships to clinicopathologic features and survival","Abstract":"PURPOSE: Gallbladder carcinoma (GC) is generally considered as a relatively rare malignancy with poor prognosis. In order to guide clinicians in selecting suitable treatment for GC patients, reliable markers predictive of poor clinical outcome are desirable. This study analyzed the expression of Polo-like kinase 1 (Plk1), Nima related kinases 7 (Nek7) and Forkhead box M1 (FoxM1) in GC tissues and their relationship to clinicopathologic features and survival. METHODS: We immunohistochemically investigated the 76 specimens of gallbladder carcinoma, pericarcinoma and normal tissues using Nek7, FoxM1 and Plk1 antibodies and analyzed the overall survival time of these 76 patients. RESULTS: There were significant correlations between the high level expression of Nek7, FoxM1 and Plk1 and the tumor differentiation, Nevin staging and metastasis. The high level expression of Nek7, FoxM1 and Plk1 was significantly associated with shorter overall survival time in univariate analysis (log-rank test), also identified as an independent prognostic factor in multivariate analysis. CONCLUSION: Nek7, FoxM1 and Plk1 were significantly associated with certain clinicopathologic indices in GC. Evaluation of Nek7, FoxM1 and Plk1 expression may be an important factor in identifying a group of poor GC prognosis.","Source":"PubMed","category":"HUMAN","training_data":"The expression of Nek7, FoxM1, and Plk1 in gallbladder cancer and their relationships to clinicopathologic features and survival PURPOSE: Gallbladder carcinoma (GC) is generally considered as a relatively rare malignancy with poor prognosis. In order to guide clinicians in selecting suitable treatment for GC patients, reliable markers predictive of poor clinical outcome are desirable. This study analyzed the expression of Polo-like kinase 1 (Plk1), Nima related kinases 7 (Nek7) and Forkhead box M1 (FoxM1) in GC tissues and their relationship to clinicopathologic features and survival. METHODS: We immunohistochemically investigated the 76 specimens of gallbladder carcinoma, pericarcinoma and normal tissues using Nek7, FoxM1 and Plk1 antibodies and analyzed the overall survival time of these 76 patients. RESULTS: There were significant correlations between the high level expression of Nek7, FoxM1 and Plk1 and the tumor differentiation, Nevin staging and metastasis. The high level expression of Nek7, FoxM1 and Plk1 was significantly associated with shorter overall survival time in univariate analysis (log-rank test), also identified as an independent prognostic factor in multivariate analysis. CONCLUSION: Nek7, FoxM1 and Plk1 were significantly associated with certain clinicopathologic indices in GC. Evaluation of Nek7, FoxM1 and Plk1 expression may be an important factor in identifying a group of poor GC prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"conditional survival patients unresectable perihilar cholangiocarcinoma background conditional survival life expectancy point time patient survived specific period presentation aim study estimate conditional survival patients unresectable perihilar cholangiocarcinoma methods patients unresectable perihilar cholangiocarcinoma two academic hospitals netherlands 2002 2012 assessed multivariable cox proportional hazards analysis performed identify risk factors associated overall survival survival estimated using kaplan meier method evaluate factors associated overall survival results total 572 patients included overall survival 42 one year 6 three years conditional chance surviving three years 15 1 year increased 38 2 years independent poor prognostic factors overall survival age 65 years tumor size 3 cm imaging bilirubin levels 250 mol l ca19 9 level presentation 1000 u ml suspected distant metastases imaging conditional survival patients without prognostic factors comparable patients survived first two years conclusion conditional chance surviving patients unresectable perihilar cholangiocarcinoma increases time poor prognostic factors become less relevant patients survived two years pubmed","probabilities":0.9799733,"Title":"Conditional survival in patients with unresectable perihilar cholangiocarcinoma","Abstract":"BACKGROUND: Conditional survival is the life expectancy from a point in time for a patient who has survived a specific period after presentation. The aim of the study was to estimate conditional survival for patients with unresectable perihilar cholangiocarcinoma. METHODS: Patients with unresectable perihilar cholangiocarcinoma from two academic hospitals in the Netherlands between 2002 and 2012 were assessed. A multivariable Cox proportional hazards analysis was performed to identify risk factors associated with overall survival. Survival was estimated using the Kaplan-Meier method to evaluate factors associated with overall survival. RESULTS: In total, 572 patients were included. Overall survival was 42% at one year and 6% at three years. The conditional chance of surviving three years was 15% at 1 year and increased to 38% at 2 years. Independent poor prognostic factors for overall survival were age ≥65 years, tumor size >3 cm on imaging, bilirubin levels (>250 μmol/L), CA19-9 level at presentation (>1000 U/ml), and suspected distant metastases on imaging. The conditional survival of patients with and without these prognostic factors was comparable after patients survived the first two or more years. CONCLUSION: The conditional chance of surviving for patients with unresectable perihilar cholangiocarcinoma increases with time. Poor prognostic factors become less relevant once patients have survived two years.","Source":"PubMed","category":"HUMAN","training_data":"Conditional survival in patients with unresectable perihilar cholangiocarcinoma BACKGROUND: Conditional survival is the life expectancy from a point in time for a patient who has survived a specific period after presentation. The aim of the study was to estimate conditional survival for patients with unresectable perihilar cholangiocarcinoma. METHODS: Patients with unresectable perihilar cholangiocarcinoma from two academic hospitals in the Netherlands between 2002 and 2012 were assessed. A multivariable Cox proportional hazards analysis was performed to identify risk factors associated with overall survival. Survival was estimated using the Kaplan-Meier method to evaluate factors associated with overall survival. RESULTS: In total, 572 patients were included. Overall survival was 42% at one year and 6% at three years. The conditional chance of surviving three years was 15% at 1 year and increased to 38% at 2 years. Independent poor prognostic factors for overall survival were age ≥65 years, tumor size >3 cm on imaging, bilirubin levels (>250 μmol/L), CA19-9 level at presentation (>1000 U/ml), and suspected distant metastases on imaging. The conditional survival of patients with and without these prognostic factors was comparable after patients survived the first two or more years. CONCLUSION: The conditional chance of surviving for patients with unresectable perihilar cholangiocarcinoma increases with time. Poor prognostic factors become less relevant once patients have survived two years. PubMed","prediction_labels":"HUMAN"},{"cleaned":"helicobacter pylori gastrointestinal malignancies helicobacter pylori infection principal trigger gastric carcinogenesis gastric cancer gc remains third leading cause cancer related death sexes worldwide big japanese study risk developing gc patients peptic ulcer disease received h pylori eradication therapy annual endoscopic surveillance mean 9 9 years significantly lower successful eradication therapy compared group persistent infection 0 21 year 0 45 year respectively p 049 according recent meta analysis h pylori eradication insufficient gc risk reduction subjects advanced precancerous conditions e intestinal metaplasia dysplasia microsimulation model suggested screening smokers age 50 u serum pepsinogens allow detect advanced gastric atrophy endoscopic follow subjects testing positive cost effective strategy reduce gc mortality taiwanese study anti h pylori igg based test treat program lower incremental cost effectiveness ratios 13 c urea breath test sexes prevent gc whereas expected years life lost gc higher incremental cost effectiveness ratios test treat programs cost effective young adults 30 69 years old elders 70 years old respect gastrointestinal malignancies gc meta analysis confirmed inverse association h pylori infection esophageal adenocarcinoma finnish study h pylori seropositivity associated increased risk biliary tract cancers multivariate adjusted 2 63 95 ci 1 08 6 37 another meta analysis showed slightly increased rate pancreatic cancer patients caga negative strains 1 30 95 ci 1 02 1 65 whereas current data suggest association h pylori colorectal neoplasms may population dependent pubmed","probabilities":0.9799733,"Title":"Helicobacter pylori and Gastrointestinal Malignancies","Abstract":"Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population dependent.","Source":"PubMed","category":"HUMAN","training_data":"Helicobacter pylori and Gastrointestinal Malignancies Helicobacter pylori infection is the principal trigger of gastric carcinogenesis and gastric cancer (GC) and remains the third leading cause of cancer-related death in both sexes worldwide. In a big Japanese study, the risk of developing GC in patients with peptic ulcer disease who received H. pylori eradication therapy and annual endoscopic surveillance for a mean of 9.9 years was significantly lower after successful eradication therapy compared to the group with persistent infection (0.21%/year and 0.45%/year, respectively, p = .049). According to a recent meta-analysis, H. pylori eradication is insufficient in GC risk reduction in subjects with advanced precancerous conditions (i.e., intestinal metaplasia and dysplasia). A microsimulation model suggested screening smokers over the age of 50 in the U.S. for serum pepsinogens. This would allow to detect advanced gastric atrophy with endoscopic follow-up of subjects testing positive as a cost-effective strategy to reduce GC mortality. In a Taiwanese study, the anti-H. pylori IgG-based test-and-treat program had lower incremental cost-effectiveness ratios than that with (13)C-urea breath test in both sexes to prevent GC whereas expected years of life lost for GC were higher and the incremental cost-effectiveness ratios of test-and-treat programs were more cost-effective in young adults (30-69 years old) than in elders (>70 years old). With respect to gastrointestinal malignancies other than GC, a meta-analysis confirmed the inverse association between H. pylori infection and esophageal adenocarcinoma. In a Finnish study, H. pylori seropositivity was associated with an increased risk of biliary tract cancers (multivariate adjusted OR 2.63; 95% CI: 1.08-6.37), another meta-analysis showed a slightly increased rate of pancreatic cancer in patients with CagA-negative strains (OR: 1.30; 95% CI: 1.02-1.65), whereas current data suggest that the association between H. pylori and colorectal neoplasms may be population dependent. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value neutrophil distribution cholangiocarcinoma aim explore relationship clinicopathological features distribution neutrophils tumor microenvironment prognosis cholangiocarcinoma methods two hundred fifty four formalin fixed paraffin embedded tissue blocks analyzed including tissues cholangiocarcinoma n 254 tumor adjacent tissues n 238 tissue sections stained cd15 using immunohistochemical staining cd15 expression detected identify distribution neutrophils local tumor microenvironment neutrophil density tumor tissues adjacent tumor tissues detected reflect inflammatory status clinical data follow information cholangiocarcinoma patients underwent surgery january 2004 december 2010 analyzed retrospectively relationship clinicopathological features distribution neutrophils prognosis patients analyzed results positive expression level cd15 significantly related tnm stage cd15 expression higher tumor tissues adjacent tissues 73 6 vs 54 6 significant differences patients high expression cd15 significantly shorter overall survival os low expression cd15 median overall survival time 39 77 mo vs 16 87 mo p 0 008 patients high cd15 expression significantly shorter disease free survival time dfs low expression cd15 median dfs 38 27 mo vs 16 83 mo p 0 029 cox multivariate analysis indicated high cd15 expression tumor tissues independent risk factor predicting os patients cholangiocarcinoma p 0 012 relative risk rr 1 601 independent risk factor predicting dfs p 0 073 rr 1 462 conclusion patients high cd15 expression cancer tissues shorter dfs os high expression cd15 independent risk factor os pubmed","probabilities":0.88235295,"Title":"Prognostic value of neutrophil distribution in cholangiocarcinoma","Abstract":"AIM: To explore the relationship of clinicopathological features and the distribution of neutrophils in the tumor microenvironment with the prognosis of cholangiocarcinoma. METHODS: Two hundred and fifty-four formalin-fixed and paraffin embedded tissue blocks were analyzed, including tissues from cholangiocarcinoma (n = 254), and tumor adjacent tissues (n = 238). Tissue sections were stained for CD15 using immunohistochemical staining. CD15 expression was detected to identify the distribution of neutrophils in the local tumor microenvironment. The neutrophil density of the tumor tissues and the adjacent tumor tissues was detected to reflect their inflammatory status. Clinical data and follow-up information of cholangiocarcinoma patients who underwent surgery from January 2004 to December 2010 were analyzed retrospectively. The relationship between clinicopathological features and the distribution of neutrophils with prognosis of the patients were analyzed. RESULTS: The positive expression level of CD15 was only significantly related to the TNM stage. CD15 expression was higher in tumor tissues than in adjacent tissues (73.6% vs 54.6%), with significant differences. Patients with high expression of CD15 had significantly shorter overall survival (OS) than those with low expression of CD15 (median overall survival time 39.77 mo vs 16.87 mo, P = 0.008). Patients with high CD15 expression had significantly shorter disease free survival time (DFS) than those with low expression of CD15 (median DFS 38.27 mo vs 16.83 mo, P = 0.029). COX multivariate analysis indicated that high CD15 expression in tumor tissues was an independent risk factor for predicting OS for patients with cholangiocarcinoma [P = 0.012, relative risk (RR) = 1.601], but it was not an independent risk factor for predicting DFS (P = 0.073, RR = 1.462). CONCLUSION: Patients with high CD15 expression in cancer tissues had shorter DFS and OS. High expression of CD15 is an independent risk factor for OS.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic value of neutrophil distribution in cholangiocarcinoma AIM: To explore the relationship of clinicopathological features and the distribution of neutrophils in the tumor microenvironment with the prognosis of cholangiocarcinoma. METHODS: Two hundred and fifty-four formalin-fixed and paraffin embedded tissue blocks were analyzed, including tissues from cholangiocarcinoma (n = 254), and tumor adjacent tissues (n = 238). Tissue sections were stained for CD15 using immunohistochemical staining. CD15 expression was detected to identify the distribution of neutrophils in the local tumor microenvironment. The neutrophil density of the tumor tissues and the adjacent tumor tissues was detected to reflect their inflammatory status. Clinical data and follow-up information of cholangiocarcinoma patients who underwent surgery from January 2004 to December 2010 were analyzed retrospectively. The relationship between clinicopathological features and the distribution of neutrophils with prognosis of the patients were analyzed. RESULTS: The positive expression level of CD15 was only significantly related to the TNM stage. CD15 expression was higher in tumor tissues than in adjacent tissues (73.6% vs 54.6%), with significant differences. Patients with high expression of CD15 had significantly shorter overall survival (OS) than those with low expression of CD15 (median overall survival time 39.77 mo vs 16.87 mo, P = 0.008). Patients with high CD15 expression had significantly shorter disease free survival time (DFS) than those with low expression of CD15 (median DFS 38.27 mo vs 16.83 mo, P = 0.029). COX multivariate analysis indicated that high CD15 expression in tumor tissues was an independent risk factor for predicting OS for patients with cholangiocarcinoma [P = 0.012, relative risk (RR) = 1.601], but it was not an independent risk factor for predicting DFS (P = 0.073, RR = 1.462). CONCLUSION: Patients with high CD15 expression in cancer tissues had shorter DFS and OS. High expression of CD15 is an independent risk factor for OS. PubMed","prediction_labels":"HUMAN"},{"cleaned":"modified glasgow prognostic score mgps good predictor indication palliative bypass surgery patients unresectable pancreatic biliary cancers background patients unresectable pancreatic biliary cancers sometimes need decompression due obstruction gastrointestinal tract biliary tract aim study determine prognostic factors associated indication palliative bypass surgery patients unresectable pancreatic biliary cancers methods april 2005 september 2011 37 patients unresectable pancreatic biliary cancers underwent palliative bypass surgery prognostic factors searched among clinical characteristics operation related factors tumor related factors using prospective database results median survival time mst patients 4 6 months 6 month survival rate 40 5 multivariate cox proportional hazards regression analysis revealed mgps 2 independent prognostic factor bypass surgery patients mgps 2 mst 1 7 months significantly worse prognosis mgps 0 1 patients mst 6 3 months conclusions mgps useful predicting survival surgical decompression due gastrointestinal obstruction patients unresectable pancreatic biliary cancers patients poor mgps may indicated palliative bypass surgery pubmed","probabilities":0.9799733,"Title":"The modified Glasgow Prognostic Score (mGPS) is a good predictor of indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers","Abstract":"BACKGROUND: Patients with unresectable pancreatic and biliary cancers sometimes need decompression due to obstruction of the gastrointestinal tract and/or biliary tract. The aim of this study was to determine the prognostic factors associated with an indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers. METHODS: Between April 2005 and September 2011, 37 patients with unresectable pancreatic and biliary cancers underwent palliative bypass surgery. Prognostic factors were searched for among clinical characteristics, operation-related factors, and tumor-related factors using a prospective database. RESULTS: The median survival time (MST) of these patients was 4.6 months, with a 6-month survival rate of 40.5 %. A multivariate Cox proportional hazards regression analysis revealed that mGPS >2 was the only independent prognostic factor for bypass surgery. Patients with an mGPS of 2 had an MST of 1.7 months, and they had a significantly worse prognosis than mGPS 0-1 patients with an MST of 6.3 months. CONCLUSIONS: The mGPS is useful for predicting survival after surgical decompression due to gastrointestinal obstruction in patients with unresectable pancreatic and biliary cancers. Patients with a poor mGPS may not be indicated for palliative bypass surgery.","Source":"PubMed","category":"HUMAN","training_data":"The modified Glasgow Prognostic Score (mGPS) is a good predictor of indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers BACKGROUND: Patients with unresectable pancreatic and biliary cancers sometimes need decompression due to obstruction of the gastrointestinal tract and/or biliary tract. The aim of this study was to determine the prognostic factors associated with an indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers. METHODS: Between April 2005 and September 2011, 37 patients with unresectable pancreatic and biliary cancers underwent palliative bypass surgery. Prognostic factors were searched for among clinical characteristics, operation-related factors, and tumor-related factors using a prospective database. RESULTS: The median survival time (MST) of these patients was 4.6 months, with a 6-month survival rate of 40.5 %. A multivariate Cox proportional hazards regression analysis revealed that mGPS >2 was the only independent prognostic factor for bypass surgery. Patients with an mGPS of 2 had an MST of 1.7 months, and they had a significantly worse prognosis than mGPS 0-1 patients with an MST of 6.3 months. CONCLUSIONS: The mGPS is useful for predicting survival after surgical decompression due to gastrointestinal obstruction in patients with unresectable pancreatic and biliary cancers. Patients with a poor mGPS may not be indicated for palliative bypass surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"unexpected pathological findings laparoscopic cholecystectomy analysis 1131 cases introduction gallbladder specimens routinely sent histopathological examination cholecystectomy order rule presence unexpected pathological findings aim establish overall incidence unexpected pathological findings patients underwent laparoscopic cholecystectomy symptomatic gallbladder disease determine whether macroscopic appearance gallbladder ultrasound examination valid method identifying patients gallbladder malignancy material methods retrospective study conducted 2013 2015 histological reports n 1131 cholecystectomy searched unexpected pathological findings cases unexpected pathological findings identified additional analysis preoperative abdominal ultrasound examination usg done determine usefulness usg diagnosis gallbladder malignancy results 1131 patients included study 356 31 47 male 774 68 43 female unexpected pathological findings present 21 cases overall incidence unexpected pathological findings 1 86 5 patients suspicious appearances gallbladder observed preoperative ultrasound examination 16 patients suspicion malignancy positive predictive value usg 0 238 conclusions incidence unexpected pathological findings laparoscopic cholecystectomy 1 86 ultrasonography low positive predictive value identifying patients malignant findings gallbladder specimen stn","probabilities":0.9799733,"Title":"Unexpected Pathological Findings After Laparoscopic Cholecystectomy - Analysis Of 1131 Cases","Abstract":"Introduction: Gallbladder specimens are routinely sent for histopathological examination after cholecystectomy in order to rule out the presence of unexpected pathological findings. \r\n\r\n Aim: To establish the overall incidence of unexpected pathological findings in patients who underwent laparoscopic cholecystectomy for symptomatic gallbladder disease and determine whether the macroscopic appearance of the gallbladder in ultrasound examination could be a valid method for identifying patients with gallbladder malignancy. \r\n\r\n Material and methods: A retrospective study was conducted between 2013 and 2015. All histological reports (n = 1131) after cholecystectomy were searched for unexpected pathological findings. In cases where unexpected pathological findings were identified the additional analysis of preoperative abdominal ultrasound examination (USG) was done to determine the usefulness of USG in diagnosis of gallbladder malignancy. \r\n\r\n Results: Of the 1131 patients included in the study, 356 (31.47%) were male and 774 (68.43%) were female. Unexpected pathological findings were present in 21 cases. The overall incidence of unexpected pathological findings was 1.86%. Only in 5 patients were suspicious appearances of gallbladder observed in preoperative ultrasound examination. In 16 patients there was no suspicion of malignancy. The positive predictive value of USG was 0.238. \r\n\r\n Conclusions: The incidence of unexpected pathological findings after laparoscopic cholecystectomy was 1.86%. Ultrasonography has low positive predictive value for identifying patients with malignant findings in a gallbladder specimen.","Source":"STN","category":"HUMAN","training_data":"Unexpected Pathological Findings After Laparoscopic Cholecystectomy - Analysis Of 1131 Cases Introduction: Gallbladder specimens are routinely sent for histopathological examination after cholecystectomy in order to rule out the presence of unexpected pathological findings. \r\n\r\n Aim: To establish the overall incidence of unexpected pathological findings in patients who underwent laparoscopic cholecystectomy for symptomatic gallbladder disease and determine whether the macroscopic appearance of the gallbladder in ultrasound examination could be a valid method for identifying patients with gallbladder malignancy. \r\n\r\n Material and methods: A retrospective study was conducted between 2013 and 2015. All histological reports (n = 1131) after cholecystectomy were searched for unexpected pathological findings. In cases where unexpected pathological findings were identified the additional analysis of preoperative abdominal ultrasound examination (USG) was done to determine the usefulness of USG in diagnosis of gallbladder malignancy. \r\n\r\n Results: Of the 1131 patients included in the study, 356 (31.47%) were male and 774 (68.43%) were female. Unexpected pathological findings were present in 21 cases. The overall incidence of unexpected pathological findings was 1.86%. Only in 5 patients were suspicious appearances of gallbladder observed in preoperative ultrasound examination. In 16 patients there was no suspicion of malignancy. The positive predictive value of USG was 0.238. \r\n\r\n Conclusions: The incidence of unexpected pathological findings after laparoscopic cholecystectomy was 1.86%. Ultrasonography has low positive predictive value for identifying patients with malignant findings in a gallbladder specimen. STN","prediction_labels":"HUMAN"},{"cleaned":"preoperative fasting hyperglycemia independent prognostic factor postoperative survival gallbladder carcinoma radical surgery background preoperative high blood glucose levels closely associated poor performance high mortality cancer patients study designed investigate relationship preoperative fasting hyperglycemia prognosis patients gallbladder cancer gbc undergoing gbc radical surgery patients methods retrospective analysis 83 eligible patients underwent gbc radical surgery 2007 2016 performed factors affecting overall survival os recurrence free survival rfs analyzed univariate multivariate analyses results 83 patients 35 42 2 preoperative fasting hyperglycemia median os enrolled patients 12 months median os patients fasting hyperglycemia surgery 18 months shorter patients normal fasting blood glucose levels surgery 47 months p 0 001 preoperative fasting hyperglycemia associated shorter survival times univariate analyses hr 3 215 95 ci 1 846 5 601 p 0 001 multivariate analysis showed patients preoperative fasting hyperglycemia lower os hr 2 832 95 ci 1 480 5 418 p 0 002 rfs hr 2 051 95 ci 1 127 3 733 p 0 019 patients normal preoperative fasting blood glucose levels conclusion preoperative fasting hyperglycemia independent indicator poor prognosis gbc patients gbc radical surgery stn","probabilities":0.9799733,"Title":"Preoperative Fasting Hyperglycemia Is An Independent Prognostic Factor For Postoperative Survival After Gallbladder Carcinoma Radical Surgery","Abstract":"Background: Preoperative high blood glucose levels are closely associated with poor performance and high mortality in cancer patients. This study was designed to investigate the relationship between preoperative fasting hyperglycemia and the prognosis of patients with gallbladder cancer (GBC) after undergoing GBC radical surgery. \r\n\r\n Patients and methods: A retrospective analysis of 83 eligible patients who underwent GBC radical surgery between 2007 and 2016 was performed. Factors affecting overall survival (OS) and recurrence-free survival (RFS) were analyzed by univariate and multivariate analyses. \r\n\r\n Results: Of the 83 patients, 35 (42.2%) had preoperative fasting hyperglycemia. The median OS of the enrolled patients was 12 months. The median OS in patients with fasting hyperglycemia before surgery was 18 months, which was shorter than for patients with normal fasting blood glucose levels before surgery (47 months, P<0.001). Preoperative fasting hyperglycemia was associated with shorter survival times in univariate analyses (HR, 3.215; 95% CI, 1.846-5.601; P<0.001). Multivariate analysis showed that patients with preoperative fasting hyperglycemia had a lower OS (HR, 2.832; 95% CI, 1.480-5.418; P=0.002) and RFS (HR, 2.051; 95% CI, 1.127-3.733; P=0.019) than patients with normal preoperative fasting blood glucose levels. \r\n\r\n Conclusion: Preoperative fasting hyperglycemia is an independent indicator of poor prognosis in GBC patients after GBC radical surgery.","Source":"STN","category":"HUMAN","training_data":"Preoperative Fasting Hyperglycemia Is An Independent Prognostic Factor For Postoperative Survival After Gallbladder Carcinoma Radical Surgery Background: Preoperative high blood glucose levels are closely associated with poor performance and high mortality in cancer patients. This study was designed to investigate the relationship between preoperative fasting hyperglycemia and the prognosis of patients with gallbladder cancer (GBC) after undergoing GBC radical surgery. \r\n\r\n Patients and methods: A retrospective analysis of 83 eligible patients who underwent GBC radical surgery between 2007 and 2016 was performed. Factors affecting overall survival (OS) and recurrence-free survival (RFS) were analyzed by univariate and multivariate analyses. \r\n\r\n Results: Of the 83 patients, 35 (42.2%) had preoperative fasting hyperglycemia. The median OS of the enrolled patients was 12 months. The median OS in patients with fasting hyperglycemia before surgery was 18 months, which was shorter than for patients with normal fasting blood glucose levels before surgery (47 months, P<0.001). Preoperative fasting hyperglycemia was associated with shorter survival times in univariate analyses (HR, 3.215; 95% CI, 1.846-5.601; P<0.001). Multivariate analysis showed that patients with preoperative fasting hyperglycemia had a lower OS (HR, 2.832; 95% CI, 1.480-5.418; P=0.002) and RFS (HR, 2.051; 95% CI, 1.127-3.733; P=0.019) than patients with normal preoperative fasting blood glucose levels. \r\n\r\n Conclusion: Preoperative fasting hyperglycemia is an independent indicator of poor prognosis in GBC patients after GBC radical surgery. STN","prediction_labels":"HUMAN"},{"cleaned":"portal vein embolization associated reduced liver failure mortality high risk resections perihilar cholangiocarcinoma check abstract link since pasted properly google scholar","probabilities":0.9799733,"Title":"Portal Vein Embolization Is Associated With Reduced Liver Failure And Mortality In High-Risk Resections For Perihilar Cholangiocarcinoma","Abstract":"Check the abstract from the link since it is not being pasted properly","Source":"Google Scholar","category":"HUMAN","training_data":"Portal Vein Embolization Is Associated With Reduced Liver Failure And Mortality In High-Risk Resections For Perihilar Cholangiocarcinoma Check the abstract from the link since it is not being pasted properly Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"population based incidence mortality biliary tract cancer sweden background incidence trends biliary tract cancer need established study investigated incidence mortality biliary tract cancer sweden 1970 2010 methods sex specific biliary tract cancer incidence mortality rates evaluated using data swedish cancer register patient register causes death register case registration separate register gallbladder cancer cancers extra hepatic bile ducts analyzed separately standardized incidence rates calculated joinpoint regression used calculate annual percent changes apc 95 confidence intervals cis results incidence non gallbladder extra hepatic cancers assessed cancer register decreased men women mid 1980 apc 4 0 95 ci 5 3 2 7 apc 6 3 95 ci 7 7 4 8 respectively whereas mortality non gallbladder extra hepatic cancers rather increased 1990 apc 2 1 95 ci 1 4 2 8 apc 2 7 95 ci 1 3 4 1 men women respectively notably mortality rate greater incidence rate assessed cancer register early 1990 onwards incidence non gallbladder extra hepatic cancers derived patient register also increased time gallbladder cancer incidence mortality rates generally decreased however incidence rates assessed patient register decreased lesser extent conclusions incidence gallbladder cancer seems decreased past decades sweden incidence trends extra hepatic tumors gallbladder cancer may however obscured reporting pubmed","probabilities":0.9799733,"Title":"The population-based incidence and mortality of biliary tract cancer in Sweden","Abstract":"BACKGROUND: The incidence trends of biliary tract cancer need to be established. This study investigated the incidence and mortality of biliary tract cancer in Sweden in 1970-2010. METHODS: Sex-specific biliary tract cancer incidence and mortality rates were evaluated using data from the Swedish Cancer Register, Patient Register and Causes of Death Register. Case registration was separate for each register. Gallbladder cancer and cancers of the extra-hepatic bile ducts were analyzed separately. Standardized incidence rates were calculated and joinpoint regression was used to calculate annual percent changes (APC) with 95% Confidence Intervals (CIs). RESULTS: The incidence of non-gallbladder extra-hepatic cancers assessed from the Cancer Register decreased in men and women from the mid 1980's (APC: -4.0, 95% CI -5.3 - -2.7 and APC -6.3, 95% CI -7.7 - -4.8, respectively), whereas the mortality of non-gallbladder extra-hepatic cancers rather increased until 1990 (APC: 2.1, 95% CI 1.4-2.8 and APC 2.7, 95% CI 1.3-4.1, in men and women respectively). Notably, the mortality rate was greater than the incidence rate as assessed from the Cancer Register from the early 1990's and onwards. The incidence of non-gallbladder extra-hepatic cancers derived from the Patient Register also increased over time. Gallbladder cancer incidence and mortality rates generally decreased. However, incidence rates assessed from the Patient Register decreased to a lesser extent. CONCLUSIONS: The incidence of gallbladder cancer seems to have decreased over the past decades in Sweden. The incidence trends for extra-hepatic tumors other than gallbladder cancer may however be obscured by under-reporting.","Source":"PubMed","category":"HUMAN","training_data":"The population-based incidence and mortality of biliary tract cancer in Sweden BACKGROUND: The incidence trends of biliary tract cancer need to be established. This study investigated the incidence and mortality of biliary tract cancer in Sweden in 1970-2010. METHODS: Sex-specific biliary tract cancer incidence and mortality rates were evaluated using data from the Swedish Cancer Register, Patient Register and Causes of Death Register. Case registration was separate for each register. Gallbladder cancer and cancers of the extra-hepatic bile ducts were analyzed separately. Standardized incidence rates were calculated and joinpoint regression was used to calculate annual percent changes (APC) with 95% Confidence Intervals (CIs). RESULTS: The incidence of non-gallbladder extra-hepatic cancers assessed from the Cancer Register decreased in men and women from the mid 1980's (APC: -4.0, 95% CI -5.3 - -2.7 and APC -6.3, 95% CI -7.7 - -4.8, respectively), whereas the mortality of non-gallbladder extra-hepatic cancers rather increased until 1990 (APC: 2.1, 95% CI 1.4-2.8 and APC 2.7, 95% CI 1.3-4.1, in men and women respectively). Notably, the mortality rate was greater than the incidence rate as assessed from the Cancer Register from the early 1990's and onwards. The incidence of non-gallbladder extra-hepatic cancers derived from the Patient Register also increased over time. Gallbladder cancer incidence and mortality rates generally decreased. However, incidence rates assessed from the Patient Register decreased to a lesser extent. CONCLUSIONS: The incidence of gallbladder cancer seems to have decreased over the past decades in Sweden. The incidence trends for extra-hepatic tumors other than gallbladder cancer may however be obscured by under-reporting. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors affecting overall survival gallbladder cancer cisplatin gemcitabine background chemotherapy ct standard care advanced gallbladder cancer gbc prognostic factors affecting overall survival os reported materials methods consecutive gbc registered 2012 2017 treated cg included completion three cycles cg cect scan abdomen done evaluate response recist criteria intended plan deliver six cycles cg patient outcomes evaluated based disease burden extended cholecystectomy ec r0 node negative simple cholecystectomy sc received chemo radiation ctrt four cycles cg locally advanced disease lagb responders un resectable received fur ther ctrt metastatic disease responders followed non responders received second line ct treatment ct ct followed ctrt prognostic factors affecting os computed univariate multivariate analysis results 459 patients 231 eligible consultation seekers incomplete ct ctrt excluded six cycles gc 35 patients achieved complete response cr 15 2 103 partial response pr 44 6 36 stable disease sd 15 6 46 disease progression pd 19 9 11 non evaluable ne 4 8 univariate analy sis burden disease ct followed ctrt response treatment type surgery significant factors affecting os median os 84 13 8 6 months respectively cr pr sd pd p 0 000 os 84 18 9 7 months ec sc lagb metastatic disease p 0 000 respectively ct yielded os 10 months ct followed ctrt 16 months p 0 008 multivari ate analysis stratification response yielded burden disease type treatment ct followed ctrt significant prognostic factors p 0 000 0 017 respectively conclusions response treatment burden disease type surgery combination ct followed ctrt significant prognostic factors affecting os google scholar","probabilities":0.9799733,"Title":"Prognostic Factors Affecting Overall Survival In Gallbladder Cancer On Cisplatin-Gemcitabine","Abstract":"Background: Chemotherapy (CT) is the standard of care in advanced\ngallbladder cancer (GBC). Prognostic factors affecting overall survival\n(OS) are being reported.\nMaterials and methods: Consecutive GBC registered between 2012\nand 2017 and treated with CG were included. At completion of\nthree cycles CG, CECT scan abdomen was done to evaluate response\n(RECIST criteria). The intended plan was to deliver six cycles of CG.\nPatient outcomes were evaluated based on disease burden: extended\ncholecystectomy (EC) (R0 and node negative), simple cholecystectomy\n(SC) (received chemo-radiation (CTRT) after four cycles CG), locally\nadvanced disease (LAGB) (responders but un-resectable received fur-\nther CTRT), metastatic disease (responders were followed up and non-\nresponders received second-line CT) treatment (CT or CT followed by\nCTRT). Prognostic factors affecting OS were computed by univariate\nand multivariate analysis Results: Out of 459 patients, 231 were eligible (Consultation seekers,\nincomplete CT, or only CTRT were excluded). After six cycles GC, 35\npatients achieved complete response(CR, 15.2%), 103 partial response\n(PR, 44.6%), 36 stable disease (SD, 15.6%), 46 disease progression (PD,\n19.9%), and 11 were non-evaluable (NE, 4.8%). On univariate analy-\nsis, burden of disease, CT followed by CTRT, response to treatment\nand type of surgery were significant factors affecting OS. The median\nOS was 84, 13, 8, and 6 months, respectively, for CR, PR, SD, and\nPD (p = 0.000). OS was 84, 18, 9, and 7 months for EC, SC, LAGB,\nand metastatic disease (p = 0.000), respectively. CT yielded OS of 10\nmonths and CT followed by CTRT 16 months (p = 0.008). Multivari-\nate analysis (after stratification for response) yielded burden of disease\nand type of treatment (CT followed by CTRT) as significant prognostic\nfactors (p = 0.000 and 0.017, respectively).\nConclusions: Response to treatment, burden of disease, type of\nsurgery, and a combination of CT followed by CTRT are significant\nprognostic factors affecting OS","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Factors Affecting Overall Survival In Gallbladder Cancer On Cisplatin-Gemcitabine Background: Chemotherapy (CT) is the standard of care in advanced\ngallbladder cancer (GBC). Prognostic factors affecting overall survival\n(OS) are being reported.\nMaterials and methods: Consecutive GBC registered between 2012\nand 2017 and treated with CG were included. At completion of\nthree cycles CG, CECT scan abdomen was done to evaluate response\n(RECIST criteria). The intended plan was to deliver six cycles of CG.\nPatient outcomes were evaluated based on disease burden: extended\ncholecystectomy (EC) (R0 and node negative), simple cholecystectomy\n(SC) (received chemo-radiation (CTRT) after four cycles CG), locally\nadvanced disease (LAGB) (responders but un-resectable received fur-\nther CTRT), metastatic disease (responders were followed up and non-\nresponders received second-line CT) treatment (CT or CT followed by\nCTRT). Prognostic factors affecting OS were computed by univariate\nand multivariate analysis Results: Out of 459 patients, 231 were eligible (Consultation seekers,\nincomplete CT, or only CTRT were excluded). After six cycles GC, 35\npatients achieved complete response(CR, 15.2%), 103 partial response\n(PR, 44.6%), 36 stable disease (SD, 15.6%), 46 disease progression (PD,\n19.9%), and 11 were non-evaluable (NE, 4.8%). On univariate analy-\nsis, burden of disease, CT followed by CTRT, response to treatment\nand type of surgery were significant factors affecting OS. The median\nOS was 84, 13, 8, and 6 months, respectively, for CR, PR, SD, and\nPD (p = 0.000). OS was 84, 18, 9, and 7 months for EC, SC, LAGB,\nand metastatic disease (p = 0.000), respectively. CT yielded OS of 10\nmonths and CT followed by CTRT 16 months (p = 0.008). Multivari-\nate analysis (after stratification for response) yielded burden of disease\nand type of treatment (CT followed by CTRT) as significant prognostic\nfactors (p = 0.000 and 0.017, respectively).\nConclusions: Response to treatment, burden of disease, type of\nsurgery, and a combination of CT followed by CTRT are significant\nprognostic factors affecting OS Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"evaluation two modified ecf regimens treatment advanced gallbladder cancer gallbladder cancer rare disease associated poor clinical outcome survival standard therapy established yet aim study evaluate efficacy safety two modified ecf regimens advanced gallbladder cancer patients clinical data 38 patients advanced gallbladder cancer treated modified ecf regimen reviewed retrospectively 21 patients received epirubicin cisplatin 5 fu lv combination therapy seventeen patients received chemotherapy epirubicin cisplatin capecitabine partial response achieved fourteen 36 84 patients median duration 5 months range 3 13 months stable disease achieved eight patients 21 05 median time progression 4 0 months 95 ci 3 62 4 58 months median overall survival 9 8 months 95 ci 7 26 12 34 months responders demonstrated better survival non responders median survival time 16 vs 6 9 months p 0 008 median survival time epirubicin cisplatin capecitabine treated patients 9 2 versus 8 9 months epirubicin cisplatin 5 fu lv treated patients statistical difference treatment groups terms survival time p 0 769 regimen related toxicity resulted least one treatment delay dosage reduction 63 2 34 2 patients respectively chemotherapy related deaths study modified ecf regimen epirubicin cisplatin 5 fu lv substituting capecitabine 5 fu lv still potentially effective therapeutic chemotherapy patients advanced gallbladder cancer toxicity manageable remarkable difference efficacy two regimens pubmed","probabilities":0.9799733,"Title":"Evaluation of two modified ECF regimens in the treatment of advanced gallbladder cancer","Abstract":"Gallbladder cancer is a rare disease and it is associated with a poor clinical outcome and survival. A standard therapy for it has not been established yet. The aim of this study is to evaluate efficacy and safety of two modified ECF regimens in advanced gallbladder cancer patients. Clinical data of 38 patients with advanced gallbladder cancer treated with modified ECF regimen were reviewed retrospectively. Of them, 21 patients received an epirubicin, cisplatin, and 5-FU/LV combination therapy. Seventeen patients received a chemotherapy of epirubicin, cisplatin, and capecitabine. Partial response was achieved in fourteen (36.84%) patients with a median duration of 5 months (range, 3-13 months), while stable disease was achieved in eight patients (21.05%). The median time to progression was 4.0 months (95% CI, 3.62-4.58 months). And the median overall survival was 9.8 months (95% CI, 7.26-12.34 months). Responders demonstrated better survival than non-responders (median survival time: 16 vs. 6.9 months, P = 0.008). The median survival time for epirubicin-, cisplatin- and capecitabine-treated patients was 9.2 versus 8.9 months for epirubicin-, cisplatin- and 5-FU/LV-treated patients. There was no statistical difference between both treatment groups in terms of survival time (P = 0.769). Regimen-related toxicity resulted in at least one treatment delay or dosage reduction in 63.2 and 34.2% patients, respectively. There were no chemotherapy-related deaths during the study. Modified ECF regimen with epirubicin, cisplatin and 5-FU/LV or substituting capecitabine for 5-FU/LV is still a potentially effective therapeutic chemotherapy for patients with advanced gallbladder cancer, and toxicity was manageable. There was no remarkable difference in efficacy between the two regimens.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of two modified ECF regimens in the treatment of advanced gallbladder cancer Gallbladder cancer is a rare disease and it is associated with a poor clinical outcome and survival. A standard therapy for it has not been established yet. The aim of this study is to evaluate efficacy and safety of two modified ECF regimens in advanced gallbladder cancer patients. Clinical data of 38 patients with advanced gallbladder cancer treated with modified ECF regimen were reviewed retrospectively. Of them, 21 patients received an epirubicin, cisplatin, and 5-FU/LV combination therapy. Seventeen patients received a chemotherapy of epirubicin, cisplatin, and capecitabine. Partial response was achieved in fourteen (36.84%) patients with a median duration of 5 months (range, 3-13 months), while stable disease was achieved in eight patients (21.05%). The median time to progression was 4.0 months (95% CI, 3.62-4.58 months). And the median overall survival was 9.8 months (95% CI, 7.26-12.34 months). Responders demonstrated better survival than non-responders (median survival time: 16 vs. 6.9 months, P = 0.008). The median survival time for epirubicin-, cisplatin- and capecitabine-treated patients was 9.2 versus 8.9 months for epirubicin-, cisplatin- and 5-FU/LV-treated patients. There was no statistical difference between both treatment groups in terms of survival time (P = 0.769). Regimen-related toxicity resulted in at least one treatment delay or dosage reduction in 63.2 and 34.2% patients, respectively. There were no chemotherapy-related deaths during the study. Modified ECF regimen with epirubicin, cisplatin and 5-FU/LV or substituting capecitabine for 5-FU/LV is still a potentially effective therapeutic chemotherapy for patients with advanced gallbladder cancer, and toxicity was manageable. There was no remarkable difference in efficacy between the two regimens. PubMed","prediction_labels":"HUMAN"},{"cleaned":"second line therapy affect outcome patients cholangiocarcinoma single institution experience introduction metastatic cholangiocarcinoma mc remains poor prognosiswith median overall survival lower 10 months inthese patients chemotherapy constitutes treatment strategy progression toa first line chemotherapy isno established second line therapy patients indeed literature data suggest limited activity second line agents without specific drug purpose study isto evaluated experience actualrole first second line chemotherapies comparing literature date materials methods retrieved data 20 consecutive mc patients referred department january 2012 december 2016 follow closed january 2017 analyzed clinical data age karnofsky performance status kps cut 80 diagnosis radiologic biopsy clinical symptoms first line chemo gemcitabine plus cisplatin gp oxaliplatin gemox second line done median overallsurvival mos calculatedusing kaplan mayer method results diagnosis median age 70 8 years range 33 84 jaundice mainsymptom 30 followingabdominal pain otherclinical manifestations 25 histological diagnosis present 17 pts 85 17 pts 85 received astandard chemotherapy ct adoublet gp gemox 9pts 45 treated second line chemo mos entire population 8 67 interquartilerange 7 0 21 5 6 9 4 43 9 70 months mo respectively receivedfirst line cthad amos 6 97 3 63 9 67 vs 13 2 8 17 23 1 mowith second line p 0 05 log ranktest significant statistically differences werefound intermsofosbetween first line gp gemox treatments p 0 17 log rank test conclusions despite small numberof patients limitsderived retrospective analysis experience confirms literature data regardingthe role second line ct selected patients goodclinical conditions google scholar","probabilities":0.9799733,"Title":"Does Second-Line Therapy Affect The Outcome Of The Patients With Cholangiocarcinoma? A Single Institution Experience","Abstract":"Introduction: Metastatic cholangiocarcinoma(MC)remains at poor prognosiswith median overall survival lower than 10 months. Inthese patients, chemotherapy constitutes the only treatment strategy. After progression toa first-line chemotherapy, there isno established second-line therapy for these patients. Indeed, literature data suggest limited activity of most second-line agents without a specific drug. The purpose of this study isto evaluated in our experience the actualrole of first and second-line chemotherapies comparing to the literature date. Materials and methods: We retrieved data of 20 consecutive MC patients referred to our Department between January 2012 and December 2016. Follow-up was closed on January 2017. We analyzed clinical data: age, Karnofsky performance status (KPS with cut-off of 80%), diagnosis(radiologic or biopsy), clinical symptoms, first-line chemo with gemcitabine plus cisplatin (GP) or oxaliplatin(GemOx) and second-line when done. Median Overallsurvival (mOS) was calculatedusing the Kaplan Mayer method. Results: At the diagnosis median age was 70.8 years (range 33 to 84). Jaundice was the mainsymptom(30%),followingabdominal pain and otherclinical manifestations (25%). Histological diagnosis was present in 17 pts (85%). Only 17 pts (85%) received astandard chemotherapy(CT) with adoublet GP or GemOX. 9pts (45%) were treated with second line chemo. mOS in the entire population was 8.67 (InterquartileRange [7.0-21.5]) and 6.9 [4.43-9.70] months (mo) respectively. Those who receivedfirst-line CThad amOS of 6.97 [3.63-9.67] vs 13.2 [8.17-23.1] mowith second-line (p¼0.05, log-ranktest).No significant statistically differences werefound intermsofOSbetween first-line GP and GemOX treatments. (p¼0.17, log-rank test).\nConclusions: Despite the small numberof patients and with the limitsderived from retrospective analysis, our experience confirms literature data regardingthe role of second-line CT in selected patients in goodclinical conditions.","Source":"Google Scholar","category":"HUMAN","training_data":"Does Second-Line Therapy Affect The Outcome Of The Patients With Cholangiocarcinoma? A Single Institution Experience Introduction: Metastatic cholangiocarcinoma(MC)remains at poor prognosiswith median overall survival lower than 10 months. Inthese patients, chemotherapy constitutes the only treatment strategy. After progression toa first-line chemotherapy, there isno established second-line therapy for these patients. Indeed, literature data suggest limited activity of most second-line agents without a specific drug. The purpose of this study isto evaluated in our experience the actualrole of first and second-line chemotherapies comparing to the literature date. Materials and methods: We retrieved data of 20 consecutive MC patients referred to our Department between January 2012 and December 2016. Follow-up was closed on January 2017. We analyzed clinical data: age, Karnofsky performance status (KPS with cut-off of 80%), diagnosis(radiologic or biopsy), clinical symptoms, first-line chemo with gemcitabine plus cisplatin (GP) or oxaliplatin(GemOx) and second-line when done. Median Overallsurvival (mOS) was calculatedusing the Kaplan Mayer method. Results: At the diagnosis median age was 70.8 years (range 33 to 84). Jaundice was the mainsymptom(30%),followingabdominal pain and otherclinical manifestations (25%). Histological diagnosis was present in 17 pts (85%). Only 17 pts (85%) received astandard chemotherapy(CT) with adoublet GP or GemOX. 9pts (45%) were treated with second line chemo. mOS in the entire population was 8.67 (InterquartileRange [7.0-21.5]) and 6.9 [4.43-9.70] months (mo) respectively. Those who receivedfirst-line CThad amOS of 6.97 [3.63-9.67] vs 13.2 [8.17-23.1] mowith second-line (p¼0.05, log-ranktest).No significant statistically differences werefound intermsofOSbetween first-line GP and GemOX treatments. (p¼0.17, log-rank test).\nConclusions: Despite the small numberof patients and with the limitsderived from retrospective analysis, our experience confirms literature data regardingthe role of second-line CT in selected patients in goodclinical conditions. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic role socs3 a20 human cholangiocarcinoma antagonist jak stat pathway suppressor cytokine signaling 3 socs3 plays integral role shaping inflammatory environment tumorigenesis disease progression cholangiocarcinoma cca however prognostic significance remains unclear although tumor necrosis factor induced protein 3 tnfaip3 also known a20 decrease socs3 expression involved regulation tumorigenesis certain malignancies role cca remains unknown study investigated expression socs3 a20 human cca tissues assess prognostic significance proteins expression socs3 a20 initially detected western blot 22 cases freshly frozen cca tumors corresponding peritumoral tissues 22 control normal bile duct tissues proteins investigated 86 cca patients immunohistochemistry ihc evaluated association clinicopathological parameters human cca results indicated socs3 expression significantly lower cca tumor tissues corresponding peritumoral biliary tissues normal bile duct tissues conversely a20 overexpressed cca tissues thus inverse correlation expression socs3 a20 discovered furthermore patients low socs3 expression high a20 expression showed dramatically lower overall survival rate proteins associated cca lymph node metastasis postoperative recurrence overall survival rate however a20 showed significant association tumor node metastasis tnm stage socs3 showed significant association tumor differentiation multivariate cox analysis revealed socs3 a20 independent prognostic indicators overall survival cca thus study demonstrated socs3 a20 represent novel prognostic factors human cca pubmed","probabilities":0.8684211,"Title":"The Prognostic Role of SOCS3 and A20 in Human Cholangiocarcinoma","Abstract":"As an antagonist of the JAK/STAT pathway, suppressor of cytokine signaling 3 (SOCS3) plays an integral role in shaping the inflammatory environment, tumorigenesis and disease progression in cholangiocarcinoma (CCA); however, its prognostic significance remains unclear. Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown. In this study, we investigated the expression of SOCS3 and A20 in human CCA tissues to assess the prognostic significance of these proteins. The expression of SOCS3 and A20 was initially detected by western blot in 22 cases of freshly frozen CCA tumors with corresponding peritumoral tissues and 22 control normal bile duct tissues. Then, these proteins were investigated in 86 CCA patients by immunohistochemistry (IHC) and were evaluated for their association with clinicopathological parameters in human CCA. The results indicated that SOCS3 expression was significantly lower in CCA tumor tissues than in corresponding peritumoral biliary tissues and normal bile duct tissues. Conversely, A20 was overexpressed in CCA tissues. Thus, an inverse correlation between the expression of SOCS3 and A20 was discovered. Furthermore, patients with low SOCS3 expression or high A20 expression showed a dramatically lower overall survival rate. These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate. However, only A20 showed a significant association with the tumor node metastasis (TNM) stage, while SOCS3 showed a significant association with tumor differentiation. Multivariate Cox analysis revealed that SOCS3 and A20 were independent prognostic indicators for overall survival in CCA. Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA.","Source":"PubMed","category":"HUMAN","training_data":"The Prognostic Role of SOCS3 and A20 in Human Cholangiocarcinoma As an antagonist of the JAK/STAT pathway, suppressor of cytokine signaling 3 (SOCS3) plays an integral role in shaping the inflammatory environment, tumorigenesis and disease progression in cholangiocarcinoma (CCA); however, its prognostic significance remains unclear. Although tumor necrosis factor α-induced protein 3 (TNFAIP3, also known as A20) can decrease SOCS3 expression and is involved in the regulation of tumorigenesis in certain malignancies, its role in CCA remains unknown. In this study, we investigated the expression of SOCS3 and A20 in human CCA tissues to assess the prognostic significance of these proteins. The expression of SOCS3 and A20 was initially detected by western blot in 22 cases of freshly frozen CCA tumors with corresponding peritumoral tissues and 22 control normal bile duct tissues. Then, these proteins were investigated in 86 CCA patients by immunohistochemistry (IHC) and were evaluated for their association with clinicopathological parameters in human CCA. The results indicated that SOCS3 expression was significantly lower in CCA tumor tissues than in corresponding peritumoral biliary tissues and normal bile duct tissues. Conversely, A20 was overexpressed in CCA tissues. Thus, an inverse correlation between the expression of SOCS3 and A20 was discovered. Furthermore, patients with low SOCS3 expression or high A20 expression showed a dramatically lower overall survival rate. These proteins were both associated with CCA lymph node metastasis, postoperative recurrence and overall survival rate. However, only A20 showed a significant association with the tumor node metastasis (TNM) stage, while SOCS3 showed a significant association with tumor differentiation. Multivariate Cox analysis revealed that SOCS3 and A20 were independent prognostic indicators for overall survival in CCA. Thus, our study demonstrated that SOCS3 and A20 represent novel prognostic factors for human CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"assessment lymph node status extrahepatic cholangiocarcinoma number versus ratio positive lymph nodes background study aimed compare utility number positive lymph nodes lymph node ratio lnr predicting survival resection extrahepatic cholangiocarcinoma methods retrospective analysis 142 consecutive patients underwent radical resection extrahepatic cholangiocarcinoma performed total 3066 regional lymph nodes resected median number nodes per patient 21 optimal cutoff values number positive nodes lnr determined using chi square scores calculated cox proportional hazards regression model results nodal disease found 59 patients 42 subsequent analysis impact nodal status survival 18 patients r1 2 resection 6 patients paraaortic nodal disease survive 5 years resection excluded optimal cutoff value number positive nodes 1 optimal cutoff value lnr 5 univariate analysis identified number positive nodes 0 1 2 p 0 005 lnr 0 0 5 5 p 0 007 significant prognostic factors multivariate analysis identified number positive nodes lnr independent prognostic factor p 0 012 5 year survival rates 64 patients positive nodes 46 patients one positive node 28 patients two positive nodes conclusions number positive lymph nodes predicts survival better lnr resection extrahepatic cholangiocarcinoma provided nodal evaluation sufficient stn","probabilities":0.9799733,"Title":"Assessment Of Lymph Node Status In Extrahepatic Cholangiocarcinoma: Number Versus Ratio Of Positive Lymph Nodes","Abstract":"Background: This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma. \r\n\r\n Methods: A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model. \r\n\r\n Results: Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or ≥2; P = 0.005) and the LNR (0, 0-5, or >5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes. \r\n\r\n Conclusions: The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.","Source":"STN","category":"HUMAN","training_data":"Assessment Of Lymph Node Status In Extrahepatic Cholangiocarcinoma: Number Versus Ratio Of Positive Lymph Nodes Background: This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma. \r\n\r\n Methods: A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model. \r\n\r\n Results: Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or ≥2; P = 0.005) and the LNR (0, 0-5, or >5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes. \r\n\r\n Conclusions: The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient. STN","prediction_labels":"HUMAN"},{"cleaned":"long term outcome prognostic factors ampulla vater carcinoma back ground aims ampullary carcinoma rare malignancy standard treatment ampullary carcinoma pancreaticoduodenectomy despite surgical resection survival rate remains low study long term survival patients ampullary carcinoma limited aimed evaluate long term survival prognostic factors patients ampullary carcinoma methods retrospectively reviewed 148 patients diagnosed ampulla vater carcinoma september 1998 october 2012 patients classified surgery group n 77 non surgery group n 71 compared survival time prognostic factors two groups results mean age surgery group younger non surgery group 59 7 10 0 vs 68 8 11 5 years p 0 031 among surgery group patients stage ii iii iv x 26 26 13 6 6 respectively mean survival time months 80 2 12 5 stage 55 1 9 9 stage ii 25 9 6 4 stage iii 28 3 5 7 stage iv surgery group prognostic factors weret stage n stageandperilymphovascularmicroinvasion ofthe77patientswithsurgery local recurrence distant metastasis occurred 31 2 follow common site metastasis liver 70 8 non surgery group patients stage ii iii iv 37 13 3 18 respectively mean survival time months 36 6 10 stage 7 7 1 4 stage ii 4 3 3 3 stage iii 9 7 3 4 stage iv non surgery group prognosticfactorsweret stage m stageandradiotherapy theoverallmediansurvival time surgery group statistically longer non surgery group 54 7 5 9 vs 20 7 5 1months p 0 001 oncoxregressionanalysis stage n stageandperilymphovascularmicroinvasionweretheindependentdeterminantsofsurvivalinpatientswithampullary carcinoma conclusions surgical resection showed longer survival time conservative treatment thelong termsurvivalwasindependentlyinfluencedbyt stage n stage regional nodal status perilymphovascular microinvasion google scholar","probabilities":0.9799733,"Title":"The Long-Term Outcome And Prognostic Factors For Ampulla Of Vater Carcinoma","Abstract":"Back ground/Aims: Ampullary carcinoma is a rare malignancy. The standard treatment for ampullary carcinoma is pancreaticoduodenectomy. Despite surgical resection, the survival rate remains low. The study for long-term survival in patients with ampullary carcinoma is limited. We aimed to evaluate the long-term survival and the prognostic factors of the patients with ampullary carcinoma. Methods: We retrospectively reviewed the 148 patients who diagnosed with ampulla of Vater carcinoma from September 1998 to October 2012. The patients were classified into surgery group (n=77) and non-surgery group (n=71). We compared survival time and prognostic factors between two groups. Results: Mean age of surgery group was younger than that of non-surgery group (59.7±10.0 vs. 68.8±11.5 years, p=0.031). Among surgery group, patients with stage I, II, III, IV and X were 26, 26, 13, 6 and 6, respectively. Mean survival time (months) was 80.2±12.5 in stage I, 55.1±9.9 in stage II, 25.9±6.4 in stage III and 28.3±5.7 in stage IV. In surgery group, prognostic factors wereT-stage,N-stageandperilymphovascularmicroinvasion.Ofthe77patientswithsurgery, local recurrence or distant metastasis occurred in 31.2% during follow-up and the most common site of metastasis was liver (70.8%). In non-surgery group, patients with stage I, II, III and IV were 37, 13, 3 and 18, respectively. Mean survival time (months) was 36.6±10 in stage I, 7.7±1.4 in stage II, 4.3±3.3 in stage III and 9.7±3.4 in stage IV. In non-surgery group,prognosticfactorswereT-stage,M-stageandradiotherapy.Theoverallmediansurvival time of surgery group was statistically longer than that of non-surgery group (54.7±5.9 vs. 20.7±5.1months,p<0.001).Oncoxregressionanalysis,T-stage,N-stageandperilymphovascularmicroinvasionweretheindependentdeterminantsofsurvivalinpatientswithampullary carcinoma. Conclusions: Surgical resection showed longer survival time than conservative treatment.Thelong-termsurvivalwasindependentlyinfluencedbyT-stage,N-stage(regional nodal status) and perilymphovascular microinvasion","Source":"Google Scholar","category":"HUMAN","training_data":"The Long-Term Outcome And Prognostic Factors For Ampulla Of Vater Carcinoma Back ground/Aims: Ampullary carcinoma is a rare malignancy. The standard treatment for ampullary carcinoma is pancreaticoduodenectomy. Despite surgical resection, the survival rate remains low. The study for long-term survival in patients with ampullary carcinoma is limited. We aimed to evaluate the long-term survival and the prognostic factors of the patients with ampullary carcinoma. Methods: We retrospectively reviewed the 148 patients who diagnosed with ampulla of Vater carcinoma from September 1998 to October 2012. The patients were classified into surgery group (n=77) and non-surgery group (n=71). We compared survival time and prognostic factors between two groups. Results: Mean age of surgery group was younger than that of non-surgery group (59.7±10.0 vs. 68.8±11.5 years, p=0.031). Among surgery group, patients with stage I, II, III, IV and X were 26, 26, 13, 6 and 6, respectively. Mean survival time (months) was 80.2±12.5 in stage I, 55.1±9.9 in stage II, 25.9±6.4 in stage III and 28.3±5.7 in stage IV. In surgery group, prognostic factors wereT-stage,N-stageandperilymphovascularmicroinvasion.Ofthe77patientswithsurgery, local recurrence or distant metastasis occurred in 31.2% during follow-up and the most common site of metastasis was liver (70.8%). In non-surgery group, patients with stage I, II, III and IV were 37, 13, 3 and 18, respectively. Mean survival time (months) was 36.6±10 in stage I, 7.7±1.4 in stage II, 4.3±3.3 in stage III and 9.7±3.4 in stage IV. In non-surgery group,prognosticfactorswereT-stage,M-stageandradiotherapy.Theoverallmediansurvival time of surgery group was statistically longer than that of non-surgery group (54.7±5.9 vs. 20.7±5.1months,p<0.001).Oncoxregressionanalysis,T-stage,N-stageandperilymphovascularmicroinvasionweretheindependentdeterminantsofsurvivalinpatientswithampullary carcinoma. Conclusions: Surgical resection showed longer survival time than conservative treatment.Thelong-termsurvivalwasindependentlyinfluencedbyT-stage,N-stage(regional nodal status) and perilymphovascular microinvasion Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"preoperative platelet albumin ratio predicts outcome patients cholangiocarcinoma background purpose study evaluate prognostic index preoperative platelet albumin ratio par patients underwent primary resection cholangiocarcinoma patients methods total 59 patients divided two groups par 72 6 10 3 72 6 10 3 according area receiver operating characteristics curve results par significantly inversely associated overall os disease free dfs survival univariate analysis par showed significance multivariate analysis os hazard ratio 6 232 95 confidence interval 1 283 30 279 p 0 023 along tumor differentiation p 0 009 nodal involvement p 0 001 intraoperative blood loss p 0 001 serum carcinoembryonic antigen cea p 0 012 high par also significantly associated poor dfs multivariate analysis hazard ratio hr 4 422 95 confidence interval ci 1 168 16 732 p 0 029 along tumor differentiation p 0 009 conclusion par useful prognostic index os dfs patients cholangiocarcinoma primary resection accumulating cases prospectively new index may reference use neoadjuvant chemotherapy pubmed","probabilities":0.9799733,"Title":"Preoperative Platelet to Albumin Ratio Predicts Outcome of Patients with Cholangiocarcinoma","Abstract":"BACKGROUND: The purpose of this study was to evaluate the prognostic index of the preoperative platelet to albumin ratio (PAR) in patients who underwent primary resection for cholangiocarcinoma. PATIENTS AND METHODS: A total of 59 patients were divided into two groups: those with PAR ≥72.6×10(3) or <72.6×10(3) according to the area under the receiver operating characteristics curve. RESULTS: PAR was significantly inversely associated with overall (OS) and disease-free (DFS) survival on univariate analysis. PAR showed significance on multivariate analysis for OS (hazard ratio=6.232, 95% confidence interval=1.283-30.279, p=0.023), along with tumor differentiation (p=0.009), nodal involvement (p=0.001), intraoperative blood loss (p=0.001), and serum carcinoembryonic antigen (CEA) (p=0.012). High PAR was also significantly associated poor DFS on multivariate analysis (hazard ratio(HR)=4.422, 95% confidence interval(CI)=1.168-16.732, p=0.029), along with tumor differentiation (p=0.009). CONCLUSION: PAR is a useful prognostic index for OS and DFS in patients with cholangiocarcinoma after primary resection. By accumulating cases prospectively, this new index may be a reference for use before neoadjuvant chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Preoperative Platelet to Albumin Ratio Predicts Outcome of Patients with Cholangiocarcinoma BACKGROUND: The purpose of this study was to evaluate the prognostic index of the preoperative platelet to albumin ratio (PAR) in patients who underwent primary resection for cholangiocarcinoma. PATIENTS AND METHODS: A total of 59 patients were divided into two groups: those with PAR ≥72.6×10(3) or <72.6×10(3) according to the area under the receiver operating characteristics curve. RESULTS: PAR was significantly inversely associated with overall (OS) and disease-free (DFS) survival on univariate analysis. PAR showed significance on multivariate analysis for OS (hazard ratio=6.232, 95% confidence interval=1.283-30.279, p=0.023), along with tumor differentiation (p=0.009), nodal involvement (p=0.001), intraoperative blood loss (p=0.001), and serum carcinoembryonic antigen (CEA) (p=0.012). High PAR was also significantly associated poor DFS on multivariate analysis (hazard ratio(HR)=4.422, 95% confidence interval(CI)=1.168-16.732, p=0.029), along with tumor differentiation (p=0.009). CONCLUSION: PAR is a useful prognostic index for OS and DFS in patients with cholangiocarcinoma after primary resection. By accumulating cases prospectively, this new index may be a reference for use before neoadjuvant chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extended cholecystectomy essential prognostic factor t1b t3 incidental gallbladder carcinoma results german registry background literature 5 year survival rates incidental gallbladder carcinoma igbc show large variations different stages lymph node status often addressed early stage carcinomas identified laparoscopy igbc radical re resection needed staging impossible without lymph node dissection comparison various survival rates impossible study aimed determine influence lymph node status survival patients stages t1 t3 igbc methods data analysis german registry used results study 709 patients igbc analyzed re resected nodal negative patients significant survival advantage re resected nodal positive patients 5 year survival rate patients nodal negative re resected t1 carcinomas 75 re resected t2 t3 nodal negative patients significantly better survival corresponding nodal positive patients influence radicalness different liver resection techniques results excluded 53 patients without radical resection known nodal positive status nodal positive patients radical re resection always show better survival rate nodal positive patients without radical re resection stage stage conclusions nodal positive status significant negative prognostic factor t1 t3 igbc patients radical re resection show better survival rate without lymph node dissection highly recommended stage t1b case t2 carcinomas lymph node dissection hepatoduodenal ligament seems minimum volume lymph node dissection required radical procedures beneficial tumors infiltrating serosa beyond stn","probabilities":0.9799733,"Title":"Extended Cholecystectomy As The Essential Prognostic Factor In T1B-T3 Incidental Gallbladder Carcinoma-Results Of The German Registry","Abstract":"Background: In the literature, the 5 year survival rates for incidental gallbladder carcinoma (IGBC) show large variations in the different T-stages because the lymph node status often is not addressed. Most early-stage carcinomas are identified by laparoscopy as IGBC, and radical re-resection is needed. Staging is impossible without lymph node dissection, so comparison between various survival rates is impossible. This study aimed to determine the influence of lymph node status on the survival of patients with stages T1 to T3 IGBC. \r\n\r\n Methods: For data analysis, the German Registry was used. \r\n\r\n Results: In this study, 709 patients with IGBC were analyzed. The re-resected nodal-negative patients had a significant survival advantage over the re-resected nodal-positive patients. The 5 year survival rate for the patients with nodal-negative re-resected T1 carcinomas was 75%. The re-resected T2 and T3 nodal-negative patients had significantly better survival than the corresponding nodal-positive patients. The influence that the radicalness of the different liver resection techniques had on these results was excluded. 53 patients without radical resection had a known nodal-positive status. Nodal-positive patients with radical re-resection always show a better survival rate than nodal-positive patients without radical re-resection, stage for stage. \r\n\r\n Conclusions: Nodal-positive status is a significant negative prognostic factor in T1 to T3 IGBC. Patients with radical re-resection show a better survival rate than those without it. Lymph node dissection is to be highly recommended up to stage T1b. In the case of T2 carcinomas, lymph node dissection of the hepatoduodenal ligament seems to be the minimum volume of lymph node dissection required, but more radical procedures could be beneficial for tumors infiltrating the serosa or beyond.","Source":"STN","category":"HUMAN","training_data":"Extended Cholecystectomy As The Essential Prognostic Factor In T1B-T3 Incidental Gallbladder Carcinoma-Results Of The German Registry Background: In the literature, the 5 year survival rates for incidental gallbladder carcinoma (IGBC) show large variations in the different T-stages because the lymph node status often is not addressed. Most early-stage carcinomas are identified by laparoscopy as IGBC, and radical re-resection is needed. Staging is impossible without lymph node dissection, so comparison between various survival rates is impossible. This study aimed to determine the influence of lymph node status on the survival of patients with stages T1 to T3 IGBC. \r\n\r\n Methods: For data analysis, the German Registry was used. \r\n\r\n Results: In this study, 709 patients with IGBC were analyzed. The re-resected nodal-negative patients had a significant survival advantage over the re-resected nodal-positive patients. The 5 year survival rate for the patients with nodal-negative re-resected T1 carcinomas was 75%. The re-resected T2 and T3 nodal-negative patients had significantly better survival than the corresponding nodal-positive patients. The influence that the radicalness of the different liver resection techniques had on these results was excluded. 53 patients without radical resection had a known nodal-positive status. Nodal-positive patients with radical re-resection always show a better survival rate than nodal-positive patients without radical re-resection, stage for stage. \r\n\r\n Conclusions: Nodal-positive status is a significant negative prognostic factor in T1 to T3 IGBC. Patients with radical re-resection show a better survival rate than those without it. Lymph node dissection is to be highly recommended up to stage T1b. In the case of T2 carcinomas, lymph node dissection of the hepatoduodenal ligament seems to be the minimum volume of lymph node dissection required, but more radical procedures could be beneficial for tumors infiltrating the serosa or beyond. STN","prediction_labels":"HUMAN"},{"cleaned":"impact reconstruction methods pathological factors survival pancreaticoduodenectomy background surgery remains mainstay therapy pancreatic head ph periampullary carcinoma pc provides chance cure improvements surgical technique increased surgical experience advances anesthesia intensive care parenteral nutrition substantially decreased surgical complications increased survival evaluate effects reconstruction type complications pathological factors survival quality life materials methods prospective study evaluate impact various reconstruction methods pancreatic remnant pancreaticoduodenectomy pathological characteristics pc patients 3 5 years patient characteristics descriptive analysis three variable methods either without stent compared chi square test multivariate analysis performed logistic regression analysis test multinomial logistic regression analysis test survival rate analyzed use kaplan meier test results forty one consecutive patients pc enrolled 23 men 56 1 18 women 43 9 median age 56 years 16 70 years 24 cases ph cancer eight cases pc four cases distal cbd cancer five cases duodenal carcinoma nine patients underwent duct mucosa pancreatico jejunostomy pj 17 patients underwent telescoping pancreatico jejunostomy pj 15 patients pancreaticogastrostomy pg pancreatic duct stented 30 patients 11 patients duct stented pj duct mucosa caused significantly less leakage longer operative reconstructive times telescoping pj associated shortest hospital stay 5 postoperative mortalities postoperative morbidities included pancreatic fistula 6 patients delayed gastric emptying 11 gi fistula 3 wound infection 12 burst abdomen 6 pulmonary infection 2 factors predisposed development pancreatic leakage included male gender preoperative albumin 30g dl pre operative hemoglobin 10g dl non pj duct mucosa type reconstruction ampullary cancers presented earlier stage better prognosis pancreatic cancer cholangiocarcinoma early stage ii negative surgical margin well moderate differentiation absence lymph node involvement significantly predicted longer survival conclusions pj duct mucosa anastomosis safe caused least pancreatic leakage least blood loss compared methods reconstruction associated early return back home prolonged disease free overall survival google scholar","probabilities":0.9799733,"Title":"Impact Of Reconstruction Methods And Pathological Factors On Survival After Pancreaticoduodenectomy","Abstract":"Background:\nSurgery remains the mainstay of therapy for pancreatic head (PH) and periampullary carcinoma (PC) and provides the only chance of cure. Improvements of surgical technique, increased surgical experience and advances in anesthesia, intensive care and parenteral nutrition have substantially decreased surgical complications and increased survival. We evaluate the effects of reconstruction type, complications and pathological factors on survival and quality of life.\nMaterials and Methods:\nThis is a prospective study to evaluate the impact of various reconstruction methods of the pancreatic remnant after pancreaticoduodenectomy and the pathological characteristics of PC patients over 3.5 years. Patient characteristics and descriptive analysis in the three variable methods either with or without stent were compared with Chi-square test. Multivariate analysis was performed with the logistic regression analysis test and multinomial logistic regression analysis test. Survival rate was analyzed by use Kaplan-Meier test.\nResults:\nForty-one consecutive patients with PC were enrolled. There were 23 men (56.1%) and 18 women (43.9%), with a median age of 56 years (16 to 70 years). There were 24 cases of PH cancer, eight cases of PC, four cases of distal CBD cancer and five cases of duodenal carcinoma. Nine patients underwent duct-to-mucosa pancreatico jejunostomy (PJ), 17 patients underwent telescoping pancreatico jejunostomy (PJ) and 15 patients pancreaticogastrostomy (PG). The pancreatic duct was stented in 30 patients while in 11 patients, the duct was not stented. The PJ duct-to-mucosa caused significantly less leakage, but longer operative and reconstructive times. Telescoping PJ was associated with the shortest hospital stay. There were 5 postoperative mortalities, while postoperative morbidities included pancreatic fistula-6 patients, delayed gastric emptying in-11, GI fistula-3, wound infection-12, burst abdomen-6 and pulmonary infection-2. Factors that predisposed to development of pancreatic leakage included male gender, preoperative albumin < 30g/dl, pre-operative hemoglobin < 10g/dl and non PJ-duct to mucosa type of reconstruction. The ampullary cancers presented at an earlier stage and had a better prognosis than pancreatic cancer and cholangiocarcinoma. Early stage (I and II), negative surgical margin, well and moderate differentiation and absence of lymph node involvement significantly predicted for longer survival.\nConclusions:\nPJ duct-to-mucosa anastomosis was safe, caused least pancreatic leakage and least blood loss compared with the other methods of reconstruction and was associated with early return back to home and prolonged disease free and overall survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Impact Of Reconstruction Methods And Pathological Factors On Survival After Pancreaticoduodenectomy Background:\nSurgery remains the mainstay of therapy for pancreatic head (PH) and periampullary carcinoma (PC) and provides the only chance of cure. Improvements of surgical technique, increased surgical experience and advances in anesthesia, intensive care and parenteral nutrition have substantially decreased surgical complications and increased survival. We evaluate the effects of reconstruction type, complications and pathological factors on survival and quality of life.\nMaterials and Methods:\nThis is a prospective study to evaluate the impact of various reconstruction methods of the pancreatic remnant after pancreaticoduodenectomy and the pathological characteristics of PC patients over 3.5 years. Patient characteristics and descriptive analysis in the three variable methods either with or without stent were compared with Chi-square test. Multivariate analysis was performed with the logistic regression analysis test and multinomial logistic regression analysis test. Survival rate was analyzed by use Kaplan-Meier test.\nResults:\nForty-one consecutive patients with PC were enrolled. There were 23 men (56.1%) and 18 women (43.9%), with a median age of 56 years (16 to 70 years). There were 24 cases of PH cancer, eight cases of PC, four cases of distal CBD cancer and five cases of duodenal carcinoma. Nine patients underwent duct-to-mucosa pancreatico jejunostomy (PJ), 17 patients underwent telescoping pancreatico jejunostomy (PJ) and 15 patients pancreaticogastrostomy (PG). The pancreatic duct was stented in 30 patients while in 11 patients, the duct was not stented. The PJ duct-to-mucosa caused significantly less leakage, but longer operative and reconstructive times. Telescoping PJ was associated with the shortest hospital stay. There were 5 postoperative mortalities, while postoperative morbidities included pancreatic fistula-6 patients, delayed gastric emptying in-11, GI fistula-3, wound infection-12, burst abdomen-6 and pulmonary infection-2. Factors that predisposed to development of pancreatic leakage included male gender, preoperative albumin < 30g/dl, pre-operative hemoglobin < 10g/dl and non PJ-duct to mucosa type of reconstruction. The ampullary cancers presented at an earlier stage and had a better prognosis than pancreatic cancer and cholangiocarcinoma. Early stage (I and II), negative surgical margin, well and moderate differentiation and absence of lymph node involvement significantly predicted for longer survival.\nConclusions:\nPJ duct-to-mucosa anastomosis was safe, caused least pancreatic leakage and least blood loss compared with the other methods of reconstruction and was associated with early return back to home and prolonged disease free and overall survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"trends incidence treatment survival gallbladder cancer nation wide cohort study introduction gallbladder cancer gbc rare lethal malignancy primarily diagnosed advanced stage unless detected incidentally laparoscopic cholecystectomy benign gallbladder disease scarce data available gbc treatment survival outcomes western populations consequently controversy exists regarding surgical systemic treatment using data netherlands cancer registry trends incidence treatment survival gbc patients evaluated methods data 2427 gbc patients diagnosed 2000 2015 included nationwide population based study incidence demographics assessed treatment strategies associated survival analysed using kaplan meier methods propensity score matching results age standardised incidence gbc varied 0 6 0 9 per 100 000 person years change significantly time demographic characteristics presented table 1 tumours 67 2 detected pre operatively overall median survival 5 2 months primarily determined tumour stage ranging 36 2 months stage patients 3 0 months stage 4 patients 2000 2015 median survival improved 4 1 6 6 months p 0 01 propensity score matching median survival surgically treated stage iii iv gallbladder cancer 7 4 months compared 3 3 months non surgically treated patients p 0 001 stage ii gbc patients receiving additional liver bed resection showed superior median survival receive additional surgery 21 7 vs 46 6 months p 0 001 systemic therapy advanced stage gbc improved median survival 2 8 7 4 months conclusion although increase 2 months overall survival demonstrated time clinical significance finding debatable outcome gbc patients still poor considerable clinically relevant increase survival seen two subgroups patients early gbc receiving additional resection patients advanced gbc treated systemic therapy aggressive treatment strategies advocated appear improve prospects gbc patients google scholar","probabilities":0.9799733,"Title":"Trends In Incidence Treatment And Survival Of Gallbladder Cancer; A Nation-Wide Cohort Study","Abstract":"Introduction: \nGallbladder cancer (GBC) is a rare but lethal malignancy, primarily diagnosed in an advanced stage unless detected incidentally after laparoscopic cholecystectomy for benign gallbladder disease. Scarce data is available on GBC treatment and survival outcomes in Western populations. Consequently, controversy exists regarding surgical and systemic treatment. Using data from the Netherlands Cancer Registry, trends in incidence, treatment and survival of GBC patients were evaluated.\nMethods:\nData of 2427 GBC patients diagnosed between 2000 – 2015 were included in this nationwide population-based study. Incidence and demographics were assessed. Treatment strategies and associated survival were analysed using Kaplan-Meier methods and propensity score matching.\nResults:\nAge-standardised incidence of GBC varied from 0.6 to 0.9 per 100.000 person years and did not change significantly over time. Demographic characteristics are presented in Table 1. Most tumours (67.2%) were detected pre-operatively. The overall median survival was 5.2 months and primarily determined by tumour stage, ranging from 36.2 months in stage I patients to 3.0 months in stage 4 patients. Between 2000 and 2015 median survival improved from 4.1 to 6.6 months (p < 0.01). After propensity score matching, median survival in surgically treated stage III + IV gallbladder cancer was 7.4 months, compared to 3.3 months for non-surgically treated patients (p < 0.001). Stage II GBC patients receiving additional liver bed resection showed superior median survival to those whom did not receive additional surgery (21.7 vs. 46.6 months, p < 0.001). Systemic therapy in advanced stage GBC improved median survival from 2.8 to 7.4 months.\nConclusion:\nAlthough an increase of 2 months in overall survival was demonstrated over time, the clinical significance of this finding is debatable and outcome of GBC patients is still poor. A considerable, clinically relevant increase in survival was seen in two subgroups: patients with early GBC receiving additional resection and patients with advanced GBC treated with systemic therapy. More aggressive treatment strategies should be advocated, as they appear to improve the prospects of GBC patients.","Source":"Google Scholar","category":"HUMAN","training_data":"Trends In Incidence Treatment And Survival Of Gallbladder Cancer; A Nation-Wide Cohort Study Introduction: \nGallbladder cancer (GBC) is a rare but lethal malignancy, primarily diagnosed in an advanced stage unless detected incidentally after laparoscopic cholecystectomy for benign gallbladder disease. Scarce data is available on GBC treatment and survival outcomes in Western populations. Consequently, controversy exists regarding surgical and systemic treatment. Using data from the Netherlands Cancer Registry, trends in incidence, treatment and survival of GBC patients were evaluated.\nMethods:\nData of 2427 GBC patients diagnosed between 2000 – 2015 were included in this nationwide population-based study. Incidence and demographics were assessed. Treatment strategies and associated survival were analysed using Kaplan-Meier methods and propensity score matching.\nResults:\nAge-standardised incidence of GBC varied from 0.6 to 0.9 per 100.000 person years and did not change significantly over time. Demographic characteristics are presented in Table 1. Most tumours (67.2%) were detected pre-operatively. The overall median survival was 5.2 months and primarily determined by tumour stage, ranging from 36.2 months in stage I patients to 3.0 months in stage 4 patients. Between 2000 and 2015 median survival improved from 4.1 to 6.6 months (p < 0.01). After propensity score matching, median survival in surgically treated stage III + IV gallbladder cancer was 7.4 months, compared to 3.3 months for non-surgically treated patients (p < 0.001). Stage II GBC patients receiving additional liver bed resection showed superior median survival to those whom did not receive additional surgery (21.7 vs. 46.6 months, p < 0.001). Systemic therapy in advanced stage GBC improved median survival from 2.8 to 7.4 months.\nConclusion:\nAlthough an increase of 2 months in overall survival was demonstrated over time, the clinical significance of this finding is debatable and outcome of GBC patients is still poor. A considerable, clinically relevant increase in survival was seen in two subgroups: patients with early GBC receiving additional resection and patients with advanced GBC treated with systemic therapy. More aggressive treatment strategies should be advocated, as they appear to improve the prospects of GBC patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"high positive lymph node ratio associated distant recurrence surgical resection ampullary carcinoma background ampullary carcinoma ac lymph node ratio lnr associated overall survival however use lnr predict distant recurrence risk remains unknown purpose study determine lnr associated distant recurrence risk methods one hundred forty three patients ac underwent pancreaticoduodenectomy 1989 2011 identified single institution prospective database data clinicopathologic factors recurrence analyzed results median follow 43 months 62 months survivors 55 patients 38 developed recurrent disease median time recurrence 13 months patients lnr 0 15 likely t3 4 tumors advanced stage lymphovascular lvi perineural invasion pni develop recurrent disease univariate analysis demonstrated stage lymph node status ajcc stage lvi pni lnr significantly associated decreased time distant recurrence ttdr multivariate stepwise regression lnr lvi significantly associated decreased ttdr conclusions high positive lnr associated distant recurrence surgical resection ac given high risk disease recurrence consideration adjuvant therapy warranted patients lnr 0 15 pubmed","probabilities":0.9799733,"Title":"A high positive lymph node ratio is associated with distant recurrence after surgical resection of ampullary carcinoma","Abstract":"BACKGROUND: For ampullary carcinoma (AC), the lymph node ratio (LNR) has been associated with overall survival. However, the use of the LNR to predict distant recurrence risk remains unknown. The purpose of this study was to determine if the LNR is associated with distant recurrence risk. METHODS: One hundred forty three patients with AC who underwent pancreaticoduodenectomy between 1989 and 2011 were identified from a single-institution prospective database. Data on clinicopathologic factors and recurrence were analyzed. RESULTS: At a median follow-up of 43 months (62 months for survivors), 55 patients (38 %) had developed recurrent disease, with a median time to recurrence of 13 months. Patients with a LNR ≥ 0.15 were more likely to have T3/4 tumors, advanced stage lymphovascular (LVI), or perineural invasion (PNI) and develop recurrent disease. Univariate analysis demonstrated that T-stage, lymph node status, AJCC stage, LVI, PNI, and LNR were significantly associated with decreased time to distant recurrence (TTDR). In multivariate stepwise regression, only LNR and LVI were significantly associated with decreased TTDR. CONCLUSIONS: A high positive LNR is associated with distant recurrence after surgical resection of AC. Given the high risk of disease recurrence, consideration for adjuvant therapy is warranted in patients with a LNR ≥ 0.15.","Source":"PubMed","category":"HUMAN","training_data":"A high positive lymph node ratio is associated with distant recurrence after surgical resection of ampullary carcinoma BACKGROUND: For ampullary carcinoma (AC), the lymph node ratio (LNR) has been associated with overall survival. However, the use of the LNR to predict distant recurrence risk remains unknown. The purpose of this study was to determine if the LNR is associated with distant recurrence risk. METHODS: One hundred forty three patients with AC who underwent pancreaticoduodenectomy between 1989 and 2011 were identified from a single-institution prospective database. Data on clinicopathologic factors and recurrence were analyzed. RESULTS: At a median follow-up of 43 months (62 months for survivors), 55 patients (38 %) had developed recurrent disease, with a median time to recurrence of 13 months. Patients with a LNR ≥ 0.15 were more likely to have T3/4 tumors, advanced stage lymphovascular (LVI), or perineural invasion (PNI) and develop recurrent disease. Univariate analysis demonstrated that T-stage, lymph node status, AJCC stage, LVI, PNI, and LNR were significantly associated with decreased time to distant recurrence (TTDR). In multivariate stepwise regression, only LNR and LVI were significantly associated with decreased TTDR. CONCLUSIONS: A high positive LNR is associated with distant recurrence after surgical resection of AC. Given the high risk of disease recurrence, consideration for adjuvant therapy is warranted in patients with a LNR ≥ 0.15. PubMed","prediction_labels":"HUMAN"},{"cleaned":"liver transplantation early intrahepatic cholangiocarcinoma international retrospective study supporting prospective assessment presence intrahepatic cholangiocarcinoma icca cirrhotic liver contraindication liver transplantation centers worldwide recent investigations shown early icca single tumors 2 cm may acceptable results liver transplantation study evaluates finding larger international multicenter cohort study group composed patients transplanted hepatocellular carcinoma decompensated cirrhosis found icca explant pathology patients divided early icca advanced disease single tumor 2 cm multifocal disease january 2000 december 2013 81 patients found icca explant 33 separate nodules icca hepatocellular carcinoma 48 icca study group within study group 15 48 31 constituted early icca group 33 48 69 advanced group significant differences groups preoperative characteristics explant median size largest tumor larger advanced group 3 1 2 5 4 4 versus 1 6 1 5 1 8 median follow 35 13 5 76 4 months 1 year 3 year 5 year cumulative risks recurrence respectively 7 18 18 early icca group versus 30 47 61 advanced icca group p 0 01 1 year 3 year 5 year actuarial survival rates respectively 93 84 65 early icca group versus 79 50 45 advanced icca group p 0 02 conclusion patients cirrhosis early icca may become candidates liver transplantation prospective multicenter clinical trial needed confirm results hepatology 2016 64 1178 1188 pubmed","probabilities":0.9799733,"Title":"Liver transplantation for very early intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment","Abstract":"The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that \"very early\" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with \"very early\" iCCA and those with \"advanced\" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the \"very early\" iCCA group and 33/48 (69%) the \"advanced\" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the \"advanced\" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188).","Source":"PubMed","category":"HUMAN","training_data":"Liver transplantation for very early intrahepatic cholangiocarcinoma: International retrospective study supporting a prospective assessment The presence of an intrahepatic cholangiocarcinoma (iCCA) in a cirrhotic liver is a contraindication for liver transplantation in most centers worldwide. Recent investigations have shown that \"very early\" iCCA (single tumors ≤2 cm) may have acceptable results after liver transplantation. This study further evaluates this finding in a larger international multicenter cohort. The study group was composed of those patients who were transplanted for hepatocellular carcinoma or decompensated cirrhosis and found to have an iCCA at explant pathology. Patients were divided into those with \"very early\" iCCA and those with \"advanced\" disease (single tumor >2 cm or multifocal disease). Between January 2000 and December 2013, 81 patients were found to have an iCCA at explant; 33 had separate nodules of iCCA and hepatocellular carcinoma, and 48 had only iCCA (study group). Within the study group, 15/48 (31%) constituted the \"very early\" iCCA group and 33/48 (69%) the \"advanced\" group. There were no significant differences between groups in preoperative characteristics. At explant, the median size of the largest tumor was larger in the \"advanced\" group (3.1 [2.5-4.4] versus 1.6 [1.5-1.8]). After a median follow-up of 35 (13.5-76.4) months, the 1-year, 3-year, and 5-year cumulative risks of recurrence were, respectively, 7%, 18%, and 18% in the very early iCCA group versus 30%, 47%, and 61% in the advanced iCCA group, P = 0.01. The 1-year, 3-year, and 5-year actuarial survival rates were, respectively, 93%, 84%, and 65% in the very early iCCA group versus 79%, 50%, and 45% in the advanced iCCA group, P = 0.02. CONCLUSION: Patients with cirrhosis and very early iCCA may become candidates for liver transplantation; a prospective multicenter clinical trial is needed to further confirm these results. (Hepatology 2016;64:1178-1188). PubMed","prediction_labels":"HUMAN"},{"cleaned":"risk factors perihilar cholangiocarcinoma hospital based case control study background aims perihilar cholangiocarcinoma pcca common form bile duct cancer arising cholangiocytes confluence hepatic ducts given diversity cholangiocarcinoma cca aetiology according location scarcity studies aetiology pcca aimed identify risk factors pcca methods total 81 patients diagnosed pcca july 2007 december 2013 162 controls matched 2 1 age sex date diagnosis included hospital based case control study potential risk factors retrospectively investigated clinical records associations pcca studied calculating odds ratios ors using conditional logistic regression analysis results univariate model prevalence choledocholithiasis 14 00 p 0 014 hepatolithiasis 12 00 p 0 021 diabetes mellitus dm 2 74 p 0 005 higher pcca patients controls heavy smoking cirrhosis marginally significant risk factors pcca p 0 1 multivariate analysis revealed association pcca hepatolithiasis choledocholithiasis dm heavy smoking adjusted ors 16 47 9 39 3 36 2 52 respectively dm heavy smoking hepatolithiasis choledocholithiasis accounted 22 5 17 1 8 5 4 8 pcca risk respectively population attributable risk percentage conclusion data showed dm heavy smoking choledocholithiasis hepatolithiasis risk factors pcca development implying pcca may share aetiological factors intrahepatic cca although classified extrahepatic cca pubmed","probabilities":0.9799733,"Title":"Risk factors for perihilar cholangiocarcinoma: a hospital-based case-control study","Abstract":"BACKGROUND & AIMS: Perihilar cholangiocarcinoma (pCCA) is the most common form of bile duct cancer, arising from cholangiocytes at the confluence of hepatic ducts. Given the diversity of cholangiocarcinoma (CCA) aetiology according to the location, and the scarcity of studies on the aetiology of pCCA, we aimed to identify the risk factors for pCCA. METHODS: A total of 81 patients diagnosed with pCCA between July 2007 and December 2013, and 162 controls matched 2:1 for age, sex and date of diagnosis were included in this hospital-based case-control study. Potential risk factors were retrospectively investigated through clinical records, and the associations with pCCA were studied by calculating the odds ratios (ORs) using conditional logistic regression analysis. RESULTS: In the univariate model, the prevalence of choledocholithiasis (OR: 14.00, P = 0.014), hepatolithiasis (OR: 12.00, P = 0.021) and diabetes mellitus (DM) (OR: 2.74, P = 0.005) was higher in pCCA patients than in controls. Heavy smoking and cirrhosis were marginally significant risk factors for pCCA (P < 0.1). Multivariate analysis revealed an association between pCCA and hepatolithiasis, choledocholithiasis, DM, and heavy smoking, each, with adjusted ORs of 16.47, 9.39, 3.36 and 2.52 respectively. DM, heavy smoking, hepatolithiasis and choledocholithiasis accounted for about 22.5%, 17.1%, 8.5% and 4.8% of pCCA risk respectively (population attributable risk percentage). CONCLUSION: Our data showed that DM, heavy smoking, choledocholithiasis and hepatolithiasis were risk factors for pCCA development, implying that pCCA may share some aetiological factors with intrahepatic CCA although it has been classified as extrahepatic CCA.","Source":"PubMed","category":"HUMAN","training_data":"Risk factors for perihilar cholangiocarcinoma: a hospital-based case-control study BACKGROUND & AIMS: Perihilar cholangiocarcinoma (pCCA) is the most common form of bile duct cancer, arising from cholangiocytes at the confluence of hepatic ducts. Given the diversity of cholangiocarcinoma (CCA) aetiology according to the location, and the scarcity of studies on the aetiology of pCCA, we aimed to identify the risk factors for pCCA. METHODS: A total of 81 patients diagnosed with pCCA between July 2007 and December 2013, and 162 controls matched 2:1 for age, sex and date of diagnosis were included in this hospital-based case-control study. Potential risk factors were retrospectively investigated through clinical records, and the associations with pCCA were studied by calculating the odds ratios (ORs) using conditional logistic regression analysis. RESULTS: In the univariate model, the prevalence of choledocholithiasis (OR: 14.00, P = 0.014), hepatolithiasis (OR: 12.00, P = 0.021) and diabetes mellitus (DM) (OR: 2.74, P = 0.005) was higher in pCCA patients than in controls. Heavy smoking and cirrhosis were marginally significant risk factors for pCCA (P < 0.1). Multivariate analysis revealed an association between pCCA and hepatolithiasis, choledocholithiasis, DM, and heavy smoking, each, with adjusted ORs of 16.47, 9.39, 3.36 and 2.52 respectively. DM, heavy smoking, hepatolithiasis and choledocholithiasis accounted for about 22.5%, 17.1%, 8.5% and 4.8% of pCCA risk respectively (population attributable risk percentage). CONCLUSION: Our data showed that DM, heavy smoking, choledocholithiasis and hepatolithiasis were risk factors for pCCA development, implying that pCCA may share some aetiological factors with intrahepatic CCA although it has been classified as extrahepatic CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"obesity related digestive diseases pathophysiology obesity growing medical public health problem worldwide many digestive diseases related obesity article current state knowledge obesity related digestive diseases pathogenesis medical metabolic consequences weight reduction discussed obesity related digestive diseases include gastroesophageal reflux disease barrett esophagus esophageal cancer colon polyp cancer nonalcoholic fatty liver disease hepatitis c related disease hepatocellular carcinoma gallstone cholangiocarcinoma pancreatic cancer although obesity related esophageal diseases associated altered mechanical humoral factors obesity related digestive diseases seem associated obesity induced altered circulating levels adipocytokines insulin resistance relationship functional gastrointestinal disease obesity debated review provides comprehensive evaluation obesity related digestive diseases including pathophysiology obesity related risk medical metabolic effects weight reduction obese subjects pubmed","probabilities":0.9799733,"Title":"Obesity-Related Digestive Diseases and Their Pathophysiology","Abstract":"Obesity is a growing medical and public health problem worldwide. Many digestive diseases are related to obesity. In this article, the current state of our knowledge of obesity-related digestive diseases, their pathogenesis, and the medical and metabolic consequences of weight reduction are discussed. Obesity-related digestive diseases include gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyp and cancer, nonalcoholic fatty liver disease, hepatitis C-related disease, hepatocellular carcinoma, gallstone, cholangiocarcinoma, and pancreatic cancer. Although obesity-related esophageal diseases are associated with altered mechanical and humoral factors, other obesity-related digestive diseases seem to be associated with obesity-induced altered circulating levels of adipocytokines and insulin resistance. The relationship between functional gastrointestinal disease and obesity has been debated. This review provides a comprehensive evaluation of the obesity-related digestive diseases, including pathophysiology, obesity-related risk, and medical and metabolic effects of weight reduction in obese subjects.","Source":"PubMed","category":"HUMAN","training_data":"Obesity-Related Digestive Diseases and Their Pathophysiology Obesity is a growing medical and public health problem worldwide. Many digestive diseases are related to obesity. In this article, the current state of our knowledge of obesity-related digestive diseases, their pathogenesis, and the medical and metabolic consequences of weight reduction are discussed. Obesity-related digestive diseases include gastroesophageal reflux disease, Barrett's esophagus, esophageal cancer, colon polyp and cancer, nonalcoholic fatty liver disease, hepatitis C-related disease, hepatocellular carcinoma, gallstone, cholangiocarcinoma, and pancreatic cancer. Although obesity-related esophageal diseases are associated with altered mechanical and humoral factors, other obesity-related digestive diseases seem to be associated with obesity-induced altered circulating levels of adipocytokines and insulin resistance. The relationship between functional gastrointestinal disease and obesity has been debated. This review provides a comprehensive evaluation of the obesity-related digestive diseases, including pathophysiology, obesity-related risk, and medical and metabolic effects of weight reduction in obese subjects. PubMed","prediction_labels":"HUMAN"},{"cleaned":"case control study comparing incidence early symptoms pancreatic biliary tract cancer objectives pancreatic ductal adenocarcinoma pdac biliary tract cancers btc often diagnosed late advanced stage population based screening programmes exist diagnosis primarily dependent symptom recognition recently symptom based cancer decision support tools cdsts introduced primary care practices throughout uk support general practitioners gps identifying patients suspected pdac however future refinement tools improve diagnostic accuracy likely necessary setting health improvement network thin primary care database includes 11 million electronic patient records 562 gp practices uk participants patients diagnosis pdac btc 2000 2010 included study along six matched controls 2773 patients pdac 848 patients btc 15 395 controls primary secondary outcome measures primary aim study determine early symptom profiles pdac btc secondary aims included comparing early symptom trends btc pdac defining symptom onset pdac evaluating trends routine blood tests nearest time diagnosis results year prior diagnosis patients pdac visited gp median 18 iqr 11 27 occasions pdac associated 11 alarm symptoms btc 8 back pain 1 33 95 ci 1 18 1 49 p 0 001 lethargy 1 42 95 ci 1 25 1 62 p 0 001 new onset diabetes 2 46 95 ci 2 16 2 80 identified unique features pdac conclusions pdac btc associated numerous early alarm symptoms cdsts therefore likely useful identifying tumours early stage inclusion unique symptoms symptoms early onset routinely performed blood tests likely improve sensitivity tools pubmed","probabilities":0.9799733,"Title":"A case-control study comparing the incidence of early symptoms in pancreatic and biliary tract cancer","Abstract":"OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers (BTC) are often diagnosed late and at an advanced stage. Population-based screening programmes do not exist and diagnosis is primarily dependent on symptom recognition. Recently symptom-based cancer decision support tools (CDSTs) have been introduced into primary care practices throughout the UK to support general practitioners (GPs) in identifying patients with suspected PDAC. However, future refinement of these tools to improve their diagnostic accuracy is likely to be necessary. SETTING: The Health Improvement Network (THIN) is a primary care database, which includes more than 11 million electronic patient records, from 562 GP practices in the UK. PARTICIPANTS: All patients with a diagnosis of PDAC or BTC between 2000 and 2010 were included in the study along with six matched controls; 2773 patients with PDAC, 848 patients with BTC and 15,395 controls. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary aim of this study was to determine the early symptom profiles of PDAC and BTC. Secondary aims included comparing early symptom trends between BTC and PDAC, defining symptom onset in PDAC and evaluating trends in routine blood tests nearest to the time of diagnosis. RESULTS: In the year prior to diagnosis, patients with PDAC visited their GP on a median of 18 (IQR 11-27) occasions. PDAC was associated with 11 alarm symptoms and BTC with 8. Back pain (OR 1.33 (95% CI 1.18 to 1.49) p<0.001), lethargy (1.42 (95% CI 1.25 to 1.62) p<0.001) and new onset diabetes (OR 2.46 (95% CI 2.16 to 2.80)) were identified as unique features of PDAC. CONCLUSIONS: PDAC and BTC are associated with numerous early alarm symptoms. CDSTs are therefore likely to be useful in identifying these tumours at an early stage. Inclusion of unique symptoms, symptoms with an early onset and routinely performed blood tests is likely to further improve the sensitivity of these tools.","Source":"PubMed","category":"HUMAN","training_data":"A case-control study comparing the incidence of early symptoms in pancreatic and biliary tract cancer OBJECTIVES: Pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancers (BTC) are often diagnosed late and at an advanced stage. Population-based screening programmes do not exist and diagnosis is primarily dependent on symptom recognition. Recently symptom-based cancer decision support tools (CDSTs) have been introduced into primary care practices throughout the UK to support general practitioners (GPs) in identifying patients with suspected PDAC. However, future refinement of these tools to improve their diagnostic accuracy is likely to be necessary. SETTING: The Health Improvement Network (THIN) is a primary care database, which includes more than 11 million electronic patient records, from 562 GP practices in the UK. PARTICIPANTS: All patients with a diagnosis of PDAC or BTC between 2000 and 2010 were included in the study along with six matched controls; 2773 patients with PDAC, 848 patients with BTC and 15,395 controls. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary aim of this study was to determine the early symptom profiles of PDAC and BTC. Secondary aims included comparing early symptom trends between BTC and PDAC, defining symptom onset in PDAC and evaluating trends in routine blood tests nearest to the time of diagnosis. RESULTS: In the year prior to diagnosis, patients with PDAC visited their GP on a median of 18 (IQR 11-27) occasions. PDAC was associated with 11 alarm symptoms and BTC with 8. Back pain (OR 1.33 (95% CI 1.18 to 1.49) p<0.001), lethargy (1.42 (95% CI 1.25 to 1.62) p<0.001) and new onset diabetes (OR 2.46 (95% CI 2.16 to 2.80)) were identified as unique features of PDAC. CONCLUSIONS: PDAC and BTC are associated with numerous early alarm symptoms. CDSTs are therefore likely to be useful in identifying these tumours at an early stage. Inclusion of unique symptoms, symptoms with an early onset and routinely performed blood tests is likely to further improve the sensitivity of these tools. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatitis b virus infection favorable prognostic factor intrahepatic cholangiocarcinoma resection aim study prognostic factors intrahepatic cholangiocarcinoma icc evaluate impact chronic hepatitis b virus hbv infection survival rate icc patients methods total 155 icc patients underwent macroscopic curative resections r0 r1 enrolled retrospective study divided group hbv infection group b without hbv infection according chronic hbv infection represented positive hepatitis b surface antigen hbsag serum liver tissue clinicopathological characteristics survival rate patients evaluated results patients underwent anatomical resection 1 3 year survival rates 60 6 32 1 respectively multivariate analyses revealed hbv infection hepatolithiasis microscopic satellite lesion lymphatic metastasis independent prognostic factors survival rate icc patients median disease free survival time patients 5 0 mo number tumors microscopic satellite lesion vascular invasion independent prognostic factors disease free survival rate patients prognostic factors affecting survival rate icc patients hbv infection without hbv infection completely consistent alkaline phosphatase 119 u l microscopic satellite lesion vascular invasion lymphatic metastasis independent factors patients hbv infection r glutamyltransferase 64 u l microscopic satellite lesion poor tumor differentiation independent factors patients without hbv infection conclusion hbv infection valuable clinical factor predicting tumor invasiveness clinical outcome icc patients icc patients hbv infection distinguished without hbv infection different clinicopathological characteristics prognostic factors outcomes surgical resection pubmed","probabilities":0.7966102,"Title":"Hepatitis B virus infection: a favorable prognostic factor for intrahepatic cholangiocarcinoma after resection","Abstract":"AIM: To study the prognostic factors for intrahepatic cholangiocarcinoma (ICC) and evaluate the impact of chronic hepatitis B virus (HBV) infection on survival rate of ICC patients. METHODS: A total of 155 ICC patients who underwent macroscopic curative resections (R0 and R1) were enrolled in this retrospective study and divided into group A with HBV infection and group B without HBV infection according to their chronic HBV infection, represented by positive hepatitis B surface antigen (HBsAg) in serum or in liver tissue. Clinicopathological characteristics and survival rate of the patients were evaluated. RESULTS: All patients underwent anatomical resection. Their 1- and 3-year survival rates were 60.6% and 32.1%, respectively. Multivariate analyses revealed that HBV infection, hepatolithiasis, microscopic satellite lesion, and lymphatic metastasis were the independent prognostic factors for the survival rate of ICC patients. The median disease-free survival time of the patients was 5.0 mo. The number of tumors, microscopic satellite lesion, and vascular invasion were the independent prognostic factors for the disease-free survival rate of the patients. The prognostic factors affecting the survival rate of ICC patients with HBV infection and those without HBV infection were not completely consistent. Alkaline phosphatase > 119 U/L, microscopic satellite lesion, vascular invasion, and lymphatic metastasis were the independent factors for the patients with HBV infection, while r-glutamyltransferase > 64 U/L, microscopic satellite lesion, and poor tumor differentiation were the independent factors for the patients without HBV infection. CONCLUSION: HBV infection is a valuable clinical factor for predicting tumor invasiveness and clinical outcome of ICC patients. ICC patients with HBV infection should be distinguished from those without HBV infection because they have different clinicopathological characteristics, prognostic factors and outcomes after surgical resection.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis B virus infection: a favorable prognostic factor for intrahepatic cholangiocarcinoma after resection AIM: To study the prognostic factors for intrahepatic cholangiocarcinoma (ICC) and evaluate the impact of chronic hepatitis B virus (HBV) infection on survival rate of ICC patients. METHODS: A total of 155 ICC patients who underwent macroscopic curative resections (R0 and R1) were enrolled in this retrospective study and divided into group A with HBV infection and group B without HBV infection according to their chronic HBV infection, represented by positive hepatitis B surface antigen (HBsAg) in serum or in liver tissue. Clinicopathological characteristics and survival rate of the patients were evaluated. RESULTS: All patients underwent anatomical resection. Their 1- and 3-year survival rates were 60.6% and 32.1%, respectively. Multivariate analyses revealed that HBV infection, hepatolithiasis, microscopic satellite lesion, and lymphatic metastasis were the independent prognostic factors for the survival rate of ICC patients. The median disease-free survival time of the patients was 5.0 mo. The number of tumors, microscopic satellite lesion, and vascular invasion were the independent prognostic factors for the disease-free survival rate of the patients. The prognostic factors affecting the survival rate of ICC patients with HBV infection and those without HBV infection were not completely consistent. Alkaline phosphatase > 119 U/L, microscopic satellite lesion, vascular invasion, and lymphatic metastasis were the independent factors for the patients with HBV infection, while r-glutamyltransferase > 64 U/L, microscopic satellite lesion, and poor tumor differentiation were the independent factors for the patients without HBV infection. CONCLUSION: HBV infection is a valuable clinical factor for predicting tumor invasiveness and clinical outcome of ICC patients. ICC patients with HBV infection should be distinguished from those without HBV infection because they have different clinicopathological characteristics, prognostic factors and outcomes after surgical resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance nodal ratio patients undergoing adjuvant chemoradiotherapy curative resection ampullary cancer objectives analyze outcome patients ampullary cancer undergone curative surgery followed adjuvant chemoradiotherapy identify prognostic factors patients methods january 1991 august 2006 71 patients ampullary cancer underwent curative resection followed adjuvant radiotherapy 38 males 33 females median age 56 years range 28 77 y postoperative radiotherapy delivered tumor bed regional lymph nodes 40 50 gy 2 gy fraction 67 patients also received intravenous 5 fluorouracil radiosensitizer median follow duration 72 months survivors results 5 isolated locoregional recurrences 20 isolated distant metastases 11 combined locoregional distant relapses 5 year locoregional relapse free overall survival rates 76 2 64 5 respectively multivariate analysis nodal ratio histologic differentiation significant prognostic factors overall survival p 0 0382 0 0331 respectively conclusions adjuvant chemoradiotherapy curative resection achieve long term survival rate patients ampullary cancer nodal ratio histologic differentiation independent prognostic factors patients pubmed","probabilities":0.9799733,"Title":"Prognostic Significance of Nodal Ratio in Patients Undergoing Adjuvant Chemoradiotherapy After Curative Resection for Ampullary Cancer","Abstract":"OBJECTIVES: To analyze the outcome of patients with ampullary cancer who had undergone curative surgery followed by adjuvant chemoradiotherapy and to identify the prognostic factors for these patients METHODS: : Between January 1991 and August 2006, 71 patients with ampullary cancer underwent curative resection followed by adjuvant radiotherapy. There were 38 males and 33 females, and median age was 56 years (range, 28 to 77 y). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40 to 50 Gy at 2 Gy/fraction; 67 patients also received intravenous 5-fluorouracil as a radiosensitizer. Median follow-up duration was 72 months for survivors. RESULTS: There were 5 isolated locoregional recurrences, 20 isolated distant metastases, and 11 combined locoregional and distant relapses. The 5-year locoregional relapse-free and overall survival rates were 76.2% and 64.5%, respectively. On multivariate analysis, nodal ratio and histologic differentiation were significant prognostic factors for overall survival (P=0.0382 and 0.0331, respectively). CONCLUSIONS: Adjuvant chemoradiotherapy after curative resection can achieve a long-term survival rate in patients with ampullary cancer. Nodal ratio and histologic differentiation are independent prognostic factors for these patients.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Significance of Nodal Ratio in Patients Undergoing Adjuvant Chemoradiotherapy After Curative Resection for Ampullary Cancer OBJECTIVES: To analyze the outcome of patients with ampullary cancer who had undergone curative surgery followed by adjuvant chemoradiotherapy and to identify the prognostic factors for these patients METHODS: : Between January 1991 and August 2006, 71 patients with ampullary cancer underwent curative resection followed by adjuvant radiotherapy. There were 38 males and 33 females, and median age was 56 years (range, 28 to 77 y). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40 to 50 Gy at 2 Gy/fraction; 67 patients also received intravenous 5-fluorouracil as a radiosensitizer. Median follow-up duration was 72 months for survivors. RESULTS: There were 5 isolated locoregional recurrences, 20 isolated distant metastases, and 11 combined locoregional and distant relapses. The 5-year locoregional relapse-free and overall survival rates were 76.2% and 64.5%, respectively. On multivariate analysis, nodal ratio and histologic differentiation were significant prognostic factors for overall survival (P=0.0382 and 0.0331, respectively). CONCLUSIONS: Adjuvant chemoradiotherapy after curative resection can achieve a long-term survival rate in patients with ampullary cancer. Nodal ratio and histologic differentiation are independent prognostic factors for these patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression insulin like growth factor receptor biomarker predicting prognosis biliary tract cancer patients carcinomas gallbladder gbca bile ducts aggressive tumors poor survival therefore essential elucidate molecular mechanisms various signaling pathways order develop effective therapies study tumor specimens 40 gbca patients 12 extrahepatic bile duct carcinoma patients 26 intrahepatic bile duct carcinoma patients usa japan investigated insulin like growth factor receptor igf ir mammalian target rapamycin mtor rapidly accelerated fibrosarcoma 1 raf 1 expression immunohistochemistry addition correlations histological type pathological stage patient outcome analyzed positive expression igf ir mtor raf 1 identified 68 73 85 specimens respectively association histological type pathological stage although positive expression rate raf 1 higher advanced stage gbca moreover patients positive expression igf ir exhibited significantly reduced survival compared negative igf ir expression conclusion igf ir mtor raf 1 highly expressed biliary tract cancer targeted therapy igf ir may effective strategy among molecules igf ir expression found useful biomarker identifying patients may benefit additional treatment stn","probabilities":0.9799733,"Title":"Expression Of Insulin-Like Growth Factor I Receptor As A Biomarker For Predicting Prognosis In Biliary Tract Cancer Patients","Abstract":"Carcinomas of the gallbladder (GBCa) and bile ducts are aggressive tumors with poor survival and it is, therefore, essential to elucidate the molecular mechanisms of the various signaling pathways in order to develop effective therapies. In this study, tumor specimens from 40 GBCa patients, 12 extrahepatic bile duct carcinoma patients and 26 intrahepatic bile duct carcinoma patients from the USA and Japan were investigated for insulin-like growth factor I receptor (IGF-IR), mammalian target of rapamycin (mTOR) and rapidly accelerated fibrosarcoma-1 (Raf-1) expression by immunohistochemistry; in addition, the correlations with histological type, pathological stage and patient outcome were analyzed. Positive expression of IGF-IR, mTOR and Raf-1 were identified in 68, 73 and 85% of the specimens, respectively. There was no association with histological type and pathological stage, although the positive expression rate of Raf-1 was higher in advanced-stage GBCa. Moreover, patients with positive expression of IGF-IR exhibited significantly reduced survival compared to those with negative IGF-IR expression. In conclusion, IGF-IR, mTOR and Raf-1 were highly expressed in biliary tract cancer and targeted therapy against IGF-IR may be an effective strategy. Among these molecules, IGF-IR expression was found to be a useful biomarker for identifying patients who may benefit from additional treatment.","Source":"STN","category":"HUMAN","training_data":"Expression Of Insulin-Like Growth Factor I Receptor As A Biomarker For Predicting Prognosis In Biliary Tract Cancer Patients Carcinomas of the gallbladder (GBCa) and bile ducts are aggressive tumors with poor survival and it is, therefore, essential to elucidate the molecular mechanisms of the various signaling pathways in order to develop effective therapies. In this study, tumor specimens from 40 GBCa patients, 12 extrahepatic bile duct carcinoma patients and 26 intrahepatic bile duct carcinoma patients from the USA and Japan were investigated for insulin-like growth factor I receptor (IGF-IR), mammalian target of rapamycin (mTOR) and rapidly accelerated fibrosarcoma-1 (Raf-1) expression by immunohistochemistry; in addition, the correlations with histological type, pathological stage and patient outcome were analyzed. Positive expression of IGF-IR, mTOR and Raf-1 were identified in 68, 73 and 85% of the specimens, respectively. There was no association with histological type and pathological stage, although the positive expression rate of Raf-1 was higher in advanced-stage GBCa. Moreover, patients with positive expression of IGF-IR exhibited significantly reduced survival compared to those with negative IGF-IR expression. In conclusion, IGF-IR, mTOR and Raf-1 were highly expressed in biliary tract cancer and targeted therapy against IGF-IR may be an effective strategy. Among these molecules, IGF-IR expression was found to be a useful biomarker for identifying patients who may benefit from additional treatment. STN","prediction_labels":"HUMAN"},{"cleaned":"epidemiology treatment outcome survival primary gallbladder cancer united states period prevalence seer database study 1973 2007 background primary gallbladder cancer gbc aggressive uncommon dismal outcomes systemic analysis epidemiology outcome survival gbc past first study examine aspects gbc diagnosed last four decades 1973 2007 usa methods frequency sessions demographic treatment performed compared among caucasian usw hispanic african american aa asian multivariate analysis survival sessions kaplan meier age adjusted performed using seer database 1973 2007 results total 12 993 gbc reported seer 1973 2007 common female 73 vs 27 p 0 0001 incidence rate 2 per million average age diagnosis 64 yrs women younger diagnosis 59 vs 69 years p 0 0001 73 gbc diagnosed advance stages among female usw 39 diagnosed age less 50 distinctive trend unique gbc fewer usw received surgery radiation p 0 01 groups indicating advance diseases differencesamong ethnic groups likelihood receiving surgery radiation andchemotherapy remained significant afteradjustment stages age year diagnosis comparable 1 yr survival 28 different groups observed 2 5 yrs survival significantly higher asian 24 17 hispanics 24 18 usw 19 13 aa 19 11 p 0 02 0 05 survival improvedconsiderably time groups asian others cox regression analysis showed age diagnosis stage marital status yearof diagnosis predictors death relative risk death increased higher stages older ages chemotherapy radiation statisticallyassociated poorer survival higher rr persons receive surgery significantly worse survival higher rr conclusions gbc rare common female 73 gbc diagnosed advance stages usw female diagnosed age younger 50 survival improvedconsiderably time remains poor studies warranted examine epidemiological survival trends google scholar","probabilities":0.9799733,"Title":"Epidemiology Treatment Outcome And Survival Of Primary Gallbladder Cancer In The United States: A Period Prevalence Seer Database Study 1973-2007","Abstract":"Background: Primary gallbladder cancer (GBC) is an aggressive, uncommon with dismal outcomes. There has been no systemic analysis of epidemiology, outcome and survival of GBC in the past. This is the first study to examine these aspects of GBC diagnosed in last four decades (1973-2007) in USA. Methods: Frequency sessions on demographic and treatment were performed and compared among Caucasian (USW), Hispanic, African-American (AA) and Asian. Multivariate analysis and survival sessions (Kaplan-Meier, age adjusted) were performed using SEER database from 1973-2007. Results: Total of 12,993 GBC were reported in SEER from 1973-2007. It is more common in female (73% vs. 27%, p <0.0001) with incidence rate of 2 per million. Average age of diagnosis is 64 yrs but women were younger at diagnosis (59 vs. 69 years, p < 0.0001). 73% of GBC were diagnosed at advance stages. Among female USW, 39% were diagnosed at age less than 50. This is a distinctive trend and unique to GBC. Fewer USW received surgery and radiation (p < 0.01) than other groups indicating advance diseases. Differencesamong all ethnic groups in likelihood of receiving surgery, radiation andchemotherapy remained significant afteradjustment for stages, age, and year of diagnosis. Comparable 1 yr survival (28%) in different groups was observed. But 2-5 yrs survival is significantly higher in Asian (24%-17%) and Hispanics (24%-18%) than USW (19%-13%) and AA (19%-11%) (p= 0.02-0.05). Survival improvedconsiderably over time in all groups but more in Asian than others. Cox regression analysis showed that age at diagnosis, stage, marital status, and yearof diagnosis were predictors of death. Relative risk of death increased with higher stages and older ages. Chemotherapy and radiation were statisticallyassociated with poorer survival and higher RR.Persons, who did not receive surgery, had significantly worse survival and higher RR. Conclusions: GBC is rare but more common in female. 73% of the GBC were diagnosed at advance stages. More USW female were diagnosed at age younger than 50. Survival improvedconsiderably over time but remains poor. More studies are warranted to examine these epidemiological and survival trends.","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology Treatment Outcome And Survival Of Primary Gallbladder Cancer In The United States: A Period Prevalence Seer Database Study 1973-2007 Background: Primary gallbladder cancer (GBC) is an aggressive, uncommon with dismal outcomes. There has been no systemic analysis of epidemiology, outcome and survival of GBC in the past. This is the first study to examine these aspects of GBC diagnosed in last four decades (1973-2007) in USA. Methods: Frequency sessions on demographic and treatment were performed and compared among Caucasian (USW), Hispanic, African-American (AA) and Asian. Multivariate analysis and survival sessions (Kaplan-Meier, age adjusted) were performed using SEER database from 1973-2007. Results: Total of 12,993 GBC were reported in SEER from 1973-2007. It is more common in female (73% vs. 27%, p <0.0001) with incidence rate of 2 per million. Average age of diagnosis is 64 yrs but women were younger at diagnosis (59 vs. 69 years, p < 0.0001). 73% of GBC were diagnosed at advance stages. Among female USW, 39% were diagnosed at age less than 50. This is a distinctive trend and unique to GBC. Fewer USW received surgery and radiation (p < 0.01) than other groups indicating advance diseases. Differencesamong all ethnic groups in likelihood of receiving surgery, radiation andchemotherapy remained significant afteradjustment for stages, age, and year of diagnosis. Comparable 1 yr survival (28%) in different groups was observed. But 2-5 yrs survival is significantly higher in Asian (24%-17%) and Hispanics (24%-18%) than USW (19%-13%) and AA (19%-11%) (p= 0.02-0.05). Survival improvedconsiderably over time in all groups but more in Asian than others. Cox regression analysis showed that age at diagnosis, stage, marital status, and yearof diagnosis were predictors of death. Relative risk of death increased with higher stages and older ages. Chemotherapy and radiation were statisticallyassociated with poorer survival and higher RR.Persons, who did not receive surgery, had significantly worse survival and higher RR. Conclusions: GBC is rare but more common in female. 73% of the GBC were diagnosed at advance stages. More USW female were diagnosed at age younger than 50. Survival improvedconsiderably over time but remains poor. More studies are warranted to examine these epidemiological and survival trends. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"new clinically based staging system perihilar cholangiocarcinoma objectives current staging systems perihilar cholangiocarcinoma pcca inadequate based surgical pathology therefore relevant unresectable patients clinical trials potential targeted therapies pcca hampered lack accurate nonoperative staging system predicting survival aimed developing clinical staging system pcca prognostic relevance pcca patients help stratify patients clinical trials methods clinical information time pcca diagnosis 413 patients seen mayo clinic rochester mn 2002 2010 retrospectively analyzed survival predictive model developed using cox proportional hazards analysis performance staging system compared current ajcc uicc american joint committee cancer union international cancer control 7th tumor node metastasis tnm staging system results eastern cooperative oncology group ecog status tumor size number vascular encasement lymph node peritoneal metastasis ca 19 9 level grouped four tier staging system median survivals stages ii iii iv patients 48 6 21 8 8 6 2 8 months hazard ratios 95 confidence interval 1 0 reference 1 7 1 1 2 6 3 1 2 0 4 7 8 7 5 2 14 5 respectively p 0 0001 staging system greater concordance statistics standard error tnm staging system 0 725 0 018 vs 0 614 0 017 indicating better performance predicting survival conclusions staging system based nonoperative information time pcca diagnosis excellent discriminatory power classify patients four prognostic stages useful clinicians design clinical trials pubmed","probabilities":0.9799733,"Title":"A new clinically based staging system for perihilar cholangiocarcinoma","Abstract":"OBJECTIVES: Current staging systems for perihilar cholangiocarcinoma (pCCA) are inadequate, as they are based on surgical pathology and therefore not relevant to unresectable patients. Clinical trials for potential targeted therapies for pCCA are hampered by the lack of an accurate, nonoperative staging system for predicting survival. We aimed at developing a clinical staging system for pCCA, which would be of prognostic relevance for all pCCA patients and help stratify patients for clinical trials. METHODS: Clinical information at the time of pCCA diagnosis of 413 patients seen at Mayo Clinic, Rochester, MN between 2002 and 2010 was retrospectively analyzed. A survival predictive model was developed using Cox proportional hazards analysis. The performance of the staging system was compared with the current AJCC/UICC (the American Joint Committee on Cancer/the Union for International Cancer Control) 7th tumor-node-metastasis (TNM) staging system. RESULTS: Eastern Cooperative Oncology Group (ECOG) status, tumor size and number, vascular encasement, lymph node and peritoneal metastasis and CA 19-9 level were grouped into a four-tier staging system. The median survivals of stages I, II, III, and IV patients were 48.6, 21.8, 8.6, and 2.8 months, with hazard ratios (95% confidence interval) of 1.0 (reference), 1.7 (1.1-2.6), 3.1 (2.0-4.7), and 8.7 (5.2-14.5), respectively (P<0.0001). This staging system had greater concordance statistics (standard error) than the TNM staging system (0.725 (0.018) vs. 0.614 (0.017)), indicating better performance in predicting survival. CONCLUSIONS: This staging system, based on nonoperative information at the time of pCCA diagnosis, has excellent discriminatory power to classify patients into four prognostic stages. It could be useful to clinicians and for the design of clinical trials.","Source":"PubMed","category":"HUMAN","training_data":"A new clinically based staging system for perihilar cholangiocarcinoma OBJECTIVES: Current staging systems for perihilar cholangiocarcinoma (pCCA) are inadequate, as they are based on surgical pathology and therefore not relevant to unresectable patients. Clinical trials for potential targeted therapies for pCCA are hampered by the lack of an accurate, nonoperative staging system for predicting survival. We aimed at developing a clinical staging system for pCCA, which would be of prognostic relevance for all pCCA patients and help stratify patients for clinical trials. METHODS: Clinical information at the time of pCCA diagnosis of 413 patients seen at Mayo Clinic, Rochester, MN between 2002 and 2010 was retrospectively analyzed. A survival predictive model was developed using Cox proportional hazards analysis. The performance of the staging system was compared with the current AJCC/UICC (the American Joint Committee on Cancer/the Union for International Cancer Control) 7th tumor-node-metastasis (TNM) staging system. RESULTS: Eastern Cooperative Oncology Group (ECOG) status, tumor size and number, vascular encasement, lymph node and peritoneal metastasis and CA 19-9 level were grouped into a four-tier staging system. The median survivals of stages I, II, III, and IV patients were 48.6, 21.8, 8.6, and 2.8 months, with hazard ratios (95% confidence interval) of 1.0 (reference), 1.7 (1.1-2.6), 3.1 (2.0-4.7), and 8.7 (5.2-14.5), respectively (P<0.0001). This staging system had greater concordance statistics (standard error) than the TNM staging system (0.725 (0.018) vs. 0.614 (0.017)), indicating better performance in predicting survival. CONCLUSIONS: This staging system, based on nonoperative information at the time of pCCA diagnosis, has excellent discriminatory power to classify patients into four prognostic stages. It could be useful to clinicians and for the design of clinical trials. PubMed","prediction_labels":"HUMAN"},{"cleaned":"sweetened beverage consumption risk biliary tract gallbladder cancer prospective study background sugar sweetened beverage consumption raises blood glucose concentration positively associated weight gain type 2 diabetes implicated development biliary tract cancer btc study examined hypothesis sweetened beverage consumption positively associated risk btc prospective study methods study population comprised 70 832 swedish adults 55 9 men age 45 83 years swedish mammography cohort cohort swedish men free cancer diabetes completed food frequency questionnaire baseline incident btc case patients ascertained linkage swedish cancer register cox proportional hazards regression model used analyze data statistical tests two sided results mean follow 13 4 years 127 extrahepatic btc case patients including 71 gallbladder cancers 21 intrahepatic btc case patients ascertained adjustment risk factors women men highest category combined sugar sweetened artificially sweetened beverage consumption statistically significantly increased risk extrahepatic btc gallbladder cancer multivariable hazard ratios two servings per day 200 ml serving sweetened beverages compared consumption 1 79 95 confidence interval ci 1 02 3 13 extrahepatic btc 2 24 95 ci 1 02 4 89 gallbladder cancer corresponding hazard ratio intrahepatic btc 1 69 95 ci 0 41 7 03 conclusions findings support hypothesis high consumption sweetened beverages may increase risk btc particularly gallbladder cancer pubmed","probabilities":0.9799733,"Title":"Sweetened Beverage Consumption and Risk of Biliary Tract and Gallbladder Cancer in a Prospective Study","Abstract":"BACKGROUND: Sugar-sweetened beverage consumption raises blood glucose concentration and has been positively associated with weight gain and type 2 diabetes, all of which have been implicated in the development of biliary tract cancer (BTC). This study examined the hypothesis that sweetened beverage consumption is positively associated with risk of BTC in a prospective study. METHODS: The study population comprised 70 832 Swedish adults (55.9% men, age 45-83 years) from the Swedish Mammography Cohort and Cohort of Swedish Men who were free of cancer and diabetes and completed a food frequency questionnaire at baseline. Incident BTC case patients were ascertained through linkage with the Swedish Cancer Register. Cox proportional hazards regression model was used to analyze the data. All statistical tests were two-sided. RESULTS: During a mean follow-up of 13.4 years, 127 extrahepatic BTC case patients (including 71 gallbladder cancers) and 21 intrahepatic BTC case patients were ascertained. After adjustment for other risk factors, women and men in the highest category of combined sugar-sweetened and artificially sweetened beverage consumption had a statistically significantly increased risk of extrahepatic BTC and gallbladder cancer. The multivariable hazard ratios for two or more servings per day (200 mL/serving) of sweetened beverages compared with no consumption were 1.79 (95% confidence interval [CI] = 1.02 to 3.13) for extrahepatic BTC and 2.24 (95% CI = 1.02 to 4.89) for gallbladder cancer. The corresponding hazard ratio for intrahepatic BTC was 1.69 (95% CI = 0.41 to 7.03). CONCLUSIONS: These findings support the hypothesis that high consumption of sweetened beverages may increase the risk of BTC, particularly gallbladder cancer.","Source":"PubMed","category":"HUMAN","training_data":"Sweetened Beverage Consumption and Risk of Biliary Tract and Gallbladder Cancer in a Prospective Study BACKGROUND: Sugar-sweetened beverage consumption raises blood glucose concentration and has been positively associated with weight gain and type 2 diabetes, all of which have been implicated in the development of biliary tract cancer (BTC). This study examined the hypothesis that sweetened beverage consumption is positively associated with risk of BTC in a prospective study. METHODS: The study population comprised 70 832 Swedish adults (55.9% men, age 45-83 years) from the Swedish Mammography Cohort and Cohort of Swedish Men who were free of cancer and diabetes and completed a food frequency questionnaire at baseline. Incident BTC case patients were ascertained through linkage with the Swedish Cancer Register. Cox proportional hazards regression model was used to analyze the data. All statistical tests were two-sided. RESULTS: During a mean follow-up of 13.4 years, 127 extrahepatic BTC case patients (including 71 gallbladder cancers) and 21 intrahepatic BTC case patients were ascertained. After adjustment for other risk factors, women and men in the highest category of combined sugar-sweetened and artificially sweetened beverage consumption had a statistically significantly increased risk of extrahepatic BTC and gallbladder cancer. The multivariable hazard ratios for two or more servings per day (200 mL/serving) of sweetened beverages compared with no consumption were 1.79 (95% confidence interval [CI] = 1.02 to 3.13) for extrahepatic BTC and 2.24 (95% CI = 1.02 to 4.89) for gallbladder cancer. The corresponding hazard ratio for intrahepatic BTC was 1.69 (95% CI = 0.41 to 7.03). CONCLUSIONS: These findings support the hypothesis that high consumption of sweetened beverages may increase the risk of BTC, particularly gallbladder cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"non coding rnas emerging molecular targets gallbladder cancer gallbladder cancer one common cancers biliary tract aggressive pathophysiology emerging global health issue although minority gallbladder cancer patients receive curative resection due late diagnosis increases survival rate lack potential target molecule early diagnosis better prognosis effective therapy gallbladder cancer triggered investigators look novel technological high throughput approaches identify potential biomarker gallbladder cancer intervention non coding rnas gallbladder cancer revealed recently non coding rnas widely implicated cancer recent reports revealed association non coding rnas micrornas mirnas long non coding rnas lncrnas gallbladder cancer present updated overview biogenesis mechanism action role non coding rnas identified cellular functions gallbladder tumorigenesis prognostic therapeutic potentials efficacies future significance developing effective biomarker future gallbladder pubmed","probabilities":0.9799733,"Title":"Non-coding RNAs as emerging molecular targets of gallbladder cancer","Abstract":"Gallbladder cancer is one of the most common cancers of biliary tract with aggressive pathophysiology, now emerging as a global health issue. Although minority of gallbladder cancer patients could receive such curative resection due to late diagnosis, this increases the survival rate. Lack of potential target molecule (s) for early diagnosis, better prognosis and effective therapy of gallbladder cancer has triggered investigators to look for novel technological or high throughput approaches to identify potential biomarker for gallbladder cancer. Intervention of non-coding RNAs in gallbladder cancer has been revealed recently. Non-coding RNAs are now widely implicated in cancer. Recent reports have revealed association of non-coding RNAs (microRNAs or miRNAs and long non-coding RNAs or lncRNAs) with gallbladder cancer. Here, we present an updated overview on the biogenesis, mechanism of action, role of non-coding RNAs, the identified cellular functions in gallbladder tumorigenesis, their prognostic & therapeutic potentials (efficacies) and future significance in developing effective biomarker(s), in future, for gallbladder.","Source":"PubMed","category":"HUMAN","training_data":"Non-coding RNAs as emerging molecular targets of gallbladder cancer Gallbladder cancer is one of the most common cancers of biliary tract with aggressive pathophysiology, now emerging as a global health issue. Although minority of gallbladder cancer patients could receive such curative resection due to late diagnosis, this increases the survival rate. Lack of potential target molecule (s) for early diagnosis, better prognosis and effective therapy of gallbladder cancer has triggered investigators to look for novel technological or high throughput approaches to identify potential biomarker for gallbladder cancer. Intervention of non-coding RNAs in gallbladder cancer has been revealed recently. Non-coding RNAs are now widely implicated in cancer. Recent reports have revealed association of non-coding RNAs (microRNAs or miRNAs and long non-coding RNAs or lncRNAs) with gallbladder cancer. Here, we present an updated overview on the biogenesis, mechanism of action, role of non-coding RNAs, the identified cellular functions in gallbladder tumorigenesis, their prognostic & therapeutic potentials (efficacies) and future significance in developing effective biomarker(s), in future, for gallbladder. PubMed","prediction_labels":"HUMAN"},{"cleaned":"molecular targets therapy cancer associated metabolic syndrome transcription growth factors metabolic syndrome ms one leading risk factors development cardiovascular diseases type ii diabetes mellitus reproductive system diseases currently cardiovascular disease reproductive history risks related ms frequently discussed also shown ms associated increased risk common cancers endometrial cancer postmenopausal breast cancer colorectal cancer biliary tract cancers liver cancer men studies required understand mechanisms involvement ms components pathogenesis malignant neoplasms changes expression transcription growth factors peripheral tissues well cancer tissues patients ms revealed transcription factors amp activated protein kinase 1 stat3 sterol regulatory element binding protein 1 peroxisome proliferator activated receptor leptin adiponectin receptors seem promising molecular targets therapy cancers associated ms pubmed","probabilities":0.88235295,"Title":"Molecular targets for the therapy of cancer associated with metabolic syndrome (transcription and growth factors)","Abstract":"Metabolic syndrome (MS) is one of the leading risk factors for the development of cardiovascular diseases, type II diabetes mellitus and reproductive system diseases. Currently, not only cardiovascular disease and reproductive history risks related with MS are frequently discussed, but it has been also shown that MS is associated with increased risk of some common cancers (endometrial cancer, postmenopausal breast cancer, colorectal cancer, biliary tract cancers and liver cancer for men). Further studies are required to understand the mechanisms of the involvement of MS components in the pathogenesis of malignant neoplasms. Changes in the expression of transcription and growth factors in the peripheral tissues as well as in cancer tissues of patients with MS were revealed. Transcription factors (AMP-activated protein kinase-1, STAT3, sterol regulatory element-binding protein-1 and peroxisome proliferator-activated receptor-γ), leptin and adiponectin receptors seem to be the most promising molecular targets for the therapy of cancers associated with MS.","Source":"PubMed","category":"HUMAN","training_data":"Molecular targets for the therapy of cancer associated with metabolic syndrome (transcription and growth factors) Metabolic syndrome (MS) is one of the leading risk factors for the development of cardiovascular diseases, type II diabetes mellitus and reproductive system diseases. Currently, not only cardiovascular disease and reproductive history risks related with MS are frequently discussed, but it has been also shown that MS is associated with increased risk of some common cancers (endometrial cancer, postmenopausal breast cancer, colorectal cancer, biliary tract cancers and liver cancer for men). Further studies are required to understand the mechanisms of the involvement of MS components in the pathogenesis of malignant neoplasms. Changes in the expression of transcription and growth factors in the peripheral tissues as well as in cancer tissues of patients with MS were revealed. Transcription factors (AMP-activated protein kinase-1, STAT3, sterol regulatory element-binding protein-1 and peroxisome proliferator-activated receptor-γ), leptin and adiponectin receptors seem to be the most promising molecular targets for the therapy of cancers associated with MS. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term outcomes patients intrahepatic cholangiocarcinoma underwent percutaneous ablation purpose assess efficacy albumin bilirubin albi grade assessing long term outcomes computed tomography ct guided percutaneous microwave ablation ct pmwa treatment patients intrahepatic cholangiocarcinoma icc methods april 2011 march 2018 78 patients underwent ct pmwa enrolled study overall survival os recurrence free survival rfs compared groups stratified albi grade child pugh score cox proportional hazard regression analyses performed determine independent predictors os rfs results median follow 22 7 months range 1 86 7 months 67 patients died cumulative 1 3 5 year os rates 89 5 52 2 35 0 respectively stratified albi grade cumulative 1 3 5 year os rates 100 69 2 25 6 patients grade 1 respectively patients albi grade 2 cumulative 1 3 5 year os rates 41 0 10 3 10 3 respectively patients hepatic function albi grade 1 significantly higher os rates patients albi grade 2 p 001 multivariate analysis showed tumor size hazard ratio hr 95 confidence interval ci 9 03 1 01 80 52 p 049 albi grade hr 95 ci 9 56 1 58 58 00 p 014 associated os tumor size hr 2 03 0 69 8 04 p 049 associated rfs conclusions preliminary data study showed albi grade effective predict long term outcomes ct pmwa iccs study necessary validate results large multi center patient cohort stn","probabilities":0.9799733,"Title":"Long-Term Outcomes Of Patients With Intrahepatic Cholangiocarcinoma Who Underwent Percutaneous Ablation","Abstract":"Purpose: To assess the efficacy of the albumin-bilirubin (ALBI) grade on assessing long-term outcomes of computed tomography (CT)-guided percutaneous microwave ablation (CT-PMWA) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: Between April 2011 and March 2018, 78 patients who underwent CT-PMWA were enrolled in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared in the groups stratified by the ALBI grade and Child-Pugh score. Cox proportional hazard regression analyses were performed to determine independent predictors of OS and RFS. \r\n\r\n Results: After a median follow-up of 22.7 months (range 1-86.7 months), 67 patients had died. The cumulative 1-, 3-, and 5-year OS rates were 89.5%, 52.2%, and 35.0%, respectively. Stratified by the ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 100%, 69.2%, and 25.6% for patients with the grade 1, respectively. For patients with the ALBI grade 2, the cumulative 1-, 3-, and 5-year OS rates were 41.0%, 10.3%, and 10.3%, respectively. Patients with a hepatic function of the ALBI grade 1 had significantly higher OS rates than patients with the ALBI grade 2 (p < .001). The multivariate analysis showed tumor size (Hazard Ratio[HR] 95% Confidence Interval[CI]:9.03[1.01-80.52], p = .049) and the ALBI grade (HR[95%CI]:9.56[1.58-58.00], p = .014) were associated with OS, and tumor size (HR: 2.03[0.69-8.04], p = .049) was associated with RFS. \r\n\r\n Conclusions: The preliminary data of this study showed the ALBI grade was effective to predict long-term outcomes of CT-PMWA in ICCs. Further study is necessary to validate our results by a large, multi-center patient cohort.","Source":"STN","category":"HUMAN","training_data":"Long-Term Outcomes Of Patients With Intrahepatic Cholangiocarcinoma Who Underwent Percutaneous Ablation Purpose: To assess the efficacy of the albumin-bilirubin (ALBI) grade on assessing long-term outcomes of computed tomography (CT)-guided percutaneous microwave ablation (CT-PMWA) in the treatment of patients with intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: Between April 2011 and March 2018, 78 patients who underwent CT-PMWA were enrolled in this study. Overall survival (OS) and recurrence-free survival (RFS) were compared in the groups stratified by the ALBI grade and Child-Pugh score. Cox proportional hazard regression analyses were performed to determine independent predictors of OS and RFS. \r\n\r\n Results: After a median follow-up of 22.7 months (range 1-86.7 months), 67 patients had died. The cumulative 1-, 3-, and 5-year OS rates were 89.5%, 52.2%, and 35.0%, respectively. Stratified by the ALBI grade, the cumulative 1-, 3-, and 5-year OS rates were 100%, 69.2%, and 25.6% for patients with the grade 1, respectively. For patients with the ALBI grade 2, the cumulative 1-, 3-, and 5-year OS rates were 41.0%, 10.3%, and 10.3%, respectively. Patients with a hepatic function of the ALBI grade 1 had significantly higher OS rates than patients with the ALBI grade 2 (p < .001). The multivariate analysis showed tumor size (Hazard Ratio[HR] 95% Confidence Interval[CI]:9.03[1.01-80.52], p = .049) and the ALBI grade (HR[95%CI]:9.56[1.58-58.00], p = .014) were associated with OS, and tumor size (HR: 2.03[0.69-8.04], p = .049) was associated with RFS. \r\n\r\n Conclusions: The preliminary data of this study showed the ALBI grade was effective to predict long-term outcomes of CT-PMWA in ICCs. Further study is necessary to validate our results by a large, multi-center patient cohort. STN","prediction_labels":"HUMAN"},{"cleaned":"predictive factors outcome patients advanced biliary tract cancer receiving gemcitabine plus cisplatin first line chemotherapy background studies clearly identified prognostic factors patients advanced biliary tract cancer btc receiving gemcitabine plus cisplatin gc acknowledged standard chemotherapy regimen objectives aim study identify predictive factors overall survival os advanced btc patients receiving gc therapy methods data 307 patients advanced btc received gc therapy first line chemotherapy institution january 2007 june 2017 reviewed retrospectively patients randomly assigned investigation validation dataset ratio 2 1 multivariate analysis conducted identify prognostic factors prognostic index proposed investigation dataset usefulness index confirmed validation dataset results multivariate analysis identified poor performance status elevated serum lactate dehydrogenase elevated neutrophil lymphocyte ratio independent unfavorable predictors patients classified three groups according factors found outcomes differed significantly among three groups p 0 0002 good vs intermediate prognosis groups p 0 005 intermediate vs poor prognosis groups index applied validation dataset os confirmed differ significantly among three groups p 0 04 good vs intermediate prognosis groups p 0 0001 intermediate vs poor prognosis groups conclusions identified three predictors os patients advanced btc receiving gc therapy study based classify patients three risk groups stn","probabilities":0.9799733,"Title":"Predictive Factors Of Outcome In Patients With Advanced Biliary Tract Cancer Receiving Gemcitabine Plus Cisplatin As First-Line Chemotherapy","Abstract":"Background: Few studies have clearly identified the prognostic factors in patients with advanced biliary tract cancer (BTC) receiving gemcitabine plus cisplatin (GC) which is acknowledged as standard chemotherapy regimen. \r\n\r\n Objectives: The aim of this study was to identify predictive factors of the overall survival (OS) in advanced BTC patients receiving GC therapy. \r\n\r\n Methods: Data of 307 patients with advanced BTC who received GC therapy as the first-line chemotherapy at our institution from January 2007 to June 2017 were reviewed retrospectively. The patients were randomly assigned to the investigation or the validation dataset at the ratio of 2:1. Multivariate analysis was conducted to identify the prognostic factors, a prognostic index is proposed from the investigation dataset, and the usefulness of this index was confirmed in the validation dataset. \r\n\r\n Results: Multivariate analysis identified poor performance status, elevated serum lactate dehydrogenase, and elevated neutrophil-to-lymphocyte ratio as independent unfavorable predictors. The patients could be classified into three groups according to these factors, and it was found that the outcomes differed significantly among the three groups (P = 0.0002, good- vs. intermediate-prognosis groups; P = 0.005, intermediate- vs. poor-prognosis groups). When this index was applied to the validation dataset, the OS was confirmed to differ significantly among the three groups (P = 0.04, good- vs. intermediate-prognosis groups, P < 0.0001, intermediate- vs. poor-prognosis groups). \r\n\r\n Conclusions: We identified three predictors of the OS in patients with advanced BTC receiving GC therapy in this study, based on which we could classify the patients into three risk groups.","Source":"STN","category":"HUMAN","training_data":"Predictive Factors Of Outcome In Patients With Advanced Biliary Tract Cancer Receiving Gemcitabine Plus Cisplatin As First-Line Chemotherapy Background: Few studies have clearly identified the prognostic factors in patients with advanced biliary tract cancer (BTC) receiving gemcitabine plus cisplatin (GC) which is acknowledged as standard chemotherapy regimen. \r\n\r\n Objectives: The aim of this study was to identify predictive factors of the overall survival (OS) in advanced BTC patients receiving GC therapy. \r\n\r\n Methods: Data of 307 patients with advanced BTC who received GC therapy as the first-line chemotherapy at our institution from January 2007 to June 2017 were reviewed retrospectively. The patients were randomly assigned to the investigation or the validation dataset at the ratio of 2:1. Multivariate analysis was conducted to identify the prognostic factors, a prognostic index is proposed from the investigation dataset, and the usefulness of this index was confirmed in the validation dataset. \r\n\r\n Results: Multivariate analysis identified poor performance status, elevated serum lactate dehydrogenase, and elevated neutrophil-to-lymphocyte ratio as independent unfavorable predictors. The patients could be classified into three groups according to these factors, and it was found that the outcomes differed significantly among the three groups (P = 0.0002, good- vs. intermediate-prognosis groups; P = 0.005, intermediate- vs. poor-prognosis groups). When this index was applied to the validation dataset, the OS was confirmed to differ significantly among the three groups (P = 0.04, good- vs. intermediate-prognosis groups, P < 0.0001, intermediate- vs. poor-prognosis groups). \r\n\r\n Conclusions: We identified three predictors of the OS in patients with advanced BTC receiving GC therapy in this study, based on which we could classify the patients into three risk groups. STN","prediction_labels":"HUMAN"},{"cleaned":"epidemiology cholangiocarcinoma adults type 2 diabetes united kingdom clinical practice research datalink background cholangiocarcinoma cca bile duct tumors rare malignancies however cca accounts 10 20 liver cancers 3 gastrointestinal cancers recently metabolic syndrome considered risk factor cca epidemiology cca patients type 2 diabetes mellitus t2dm well characterized objectives calculate incidence prevalence rates cca adults witht2dm compared general population without diabetes u k methods electronic medical records 17 million adults 18 years old enrolled u k clinical practice research datalink cprd january 2007 april 2018 used calculate incidence per 100 000 person years prevalence cca among adults witht2dm adults without diabetes read diagnosis codes used define cca t2dm results stratified gender age groups body mass index bmi categories kg m2 18 5 underweight 18 5 24 9 healthy weight 25 0 29 9 overweight 30 0 34 9 obese 35 0 39 9 severely obese 40 0 morbidly obese results analysis period total 502 615 adults t2dm 16 628 872 adults without diabetes followed incidence rate per 100 000 person years cca among patients t2dm 11 0 95 ci 10 0 13 0 without diabetes 1 0 95 ci 1 0 2 0 corresponding prevalence rates 0 13 0 02 respectively difference epidemiology cca men women t2dm rates increasing age incidence 18 44 years 2 0 45 54 years 6 0 55 64 years 8 0 65 74 years 20 75 years 17 prevalence 18 44 years 0 02 45 54 years 0 05 55 64 years 0 08 65 74 years 0 18 75 years 0 16 unlike general population rates increased bmi rates bimodal among t2dm higher rates observed underweight overweight patients incidence underweight 20 healthy weight 10 overweight 12 obese 10 severely obese 10 morbidly obese 10 prevalence underweight 0 34 healthy weight 0 16 overweight 0 14 obese 0 11 severely obese 0 10 morbidly obese 0 09 conclusions compared general population patients t2dm markedly higher incidence prevalence rates cca google scholar","probabilities":0.9799733,"Title":"Epidemiology Of Cholangiocarcinoma In Adults With Type 2 Diabetes In The United Kingdom Clinical Practice Research Datalink","Abstract":"Background: Cholangiocarcinoma (CCA) and other bile duct tumors\nare rare malignancies; however, CCA accounts for 10–20% of all liver\ncancers and 3% of all gastrointestinal cancers. Recently, metabolic\nsyndrome has been considered as a risk factor for CCA, but the epidemiology\nof CCA in patients with type 2 diabetes mellitus (T2DM) is not\nwell characterized.\nObjectives: To calculate the incidence and prevalence rates of CCA in\nadults withT2DM compared to general population without diabetes in\nthe U.K.\nMethods: Electronic medical records of >17 million adults (≥18 years\nold) enrolled in the U.K. Clinical Practice Research Datalink (CPRD)\nbetween January 2007 and April 2018 were used to calculate the incidence\n(per 100,000 person‐years) and prevalence (in %) of CCA\namong adults withT2DM and adults without diabetes. Read diagnosis\ncodes were used to define CCA and T2DM. Results were stratified by\ngender, age groups, and body mass index (BMI) categories of (in kg/\nm2) <18.5 (underweight); 18.5–24.9 (healthy weight); 25.0–29.9\n(overweight); 30.0–34.9 (obese); 35.0–39.9 (severely obese);\nand ≥ 40.0 (morbidly obese).\nResults: During the analysis period, a total of 502,615 adults with\nT2DM and 16,628,872 adults without diabetes were followed.\nThe incidence rate (per 100,000 person‐years) of CCA among\npatients with T2DM was 11.0 (95%CI = 10.0–13.0), and in those\nwithout diabetes was 1.0 (95%CI = 1.0–2.0). Corresponding prevalence\nrates were 0.13% and 0.02%, respectively. There was no\ndifference in the epidemiology of CCA between men and women\nwith T2DM. The rates were increasing with age: incidence (18–\n44 years, 2.0; 45–54 years, 6.0; 55–64 years, 8.0; 65–74 years,\n20; and ≥ 75 years, 17); prevalence (18–44 years, 0.02%; 45–\n54 years, 0.05%; 55–64 years, 0.08%; 65–74 years, 0.18%;\nand ≥ 75 years, 0.16%). Unlike general population, where rates\nincreased by BMI, the rates were bimodal among those with\nT2DM, where higher rates observed in underweight and overweight\npatients: incidence (underweight, 20; healthy weight, 10;\noverweight, 12; obese, 10; severely obese, 10; and morbidly\nobese, 10); prevalence (underweight, 0.34%; healthy weight,\n0.16%; overweight, 0.14%; obese, 0.11%; severely obese, 0.10%;\nand morbidly obese, 0.09%).\nConclusions: Compared to general population, patients with T2DM\nhave markedly higher incidence and prevalence rates of CCA.","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology Of Cholangiocarcinoma In Adults With Type 2 Diabetes In The United Kingdom Clinical Practice Research Datalink Background: Cholangiocarcinoma (CCA) and other bile duct tumors\nare rare malignancies; however, CCA accounts for 10–20% of all liver\ncancers and 3% of all gastrointestinal cancers. Recently, metabolic\nsyndrome has been considered as a risk factor for CCA, but the epidemiology\nof CCA in patients with type 2 diabetes mellitus (T2DM) is not\nwell characterized.\nObjectives: To calculate the incidence and prevalence rates of CCA in\nadults withT2DM compared to general population without diabetes in\nthe U.K.\nMethods: Electronic medical records of >17 million adults (≥18 years\nold) enrolled in the U.K. Clinical Practice Research Datalink (CPRD)\nbetween January 2007 and April 2018 were used to calculate the incidence\n(per 100,000 person‐years) and prevalence (in %) of CCA\namong adults withT2DM and adults without diabetes. Read diagnosis\ncodes were used to define CCA and T2DM. Results were stratified by\ngender, age groups, and body mass index (BMI) categories of (in kg/\nm2) <18.5 (underweight); 18.5–24.9 (healthy weight); 25.0–29.9\n(overweight); 30.0–34.9 (obese); 35.0–39.9 (severely obese);\nand ≥ 40.0 (morbidly obese).\nResults: During the analysis period, a total of 502,615 adults with\nT2DM and 16,628,872 adults without diabetes were followed.\nThe incidence rate (per 100,000 person‐years) of CCA among\npatients with T2DM was 11.0 (95%CI = 10.0–13.0), and in those\nwithout diabetes was 1.0 (95%CI = 1.0–2.0). Corresponding prevalence\nrates were 0.13% and 0.02%, respectively. There was no\ndifference in the epidemiology of CCA between men and women\nwith T2DM. The rates were increasing with age: incidence (18–\n44 years, 2.0; 45–54 years, 6.0; 55–64 years, 8.0; 65–74 years,\n20; and ≥ 75 years, 17); prevalence (18–44 years, 0.02%; 45–\n54 years, 0.05%; 55–64 years, 0.08%; 65–74 years, 0.18%;\nand ≥ 75 years, 0.16%). Unlike general population, where rates\nincreased by BMI, the rates were bimodal among those with\nT2DM, where higher rates observed in underweight and overweight\npatients: incidence (underweight, 20; healthy weight, 10;\noverweight, 12; obese, 10; severely obese, 10; and morbidly\nobese, 10); prevalence (underweight, 0.34%; healthy weight,\n0.16%; overweight, 0.14%; obese, 0.11%; severely obese, 0.10%;\nand morbidly obese, 0.09%).\nConclusions: Compared to general population, patients with T2DM\nhave markedly higher incidence and prevalence rates of CCA. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"expression cdx2 hepatocyte antigen benign malignant lesions gallbladder correlation histopathologic type clinical outcome recent studies shown cdx2 hepatocyte antigen hep detected different types cancer associated clinical prognosis however fever studies examined gallbladder cancer specimens little known clinicopathological significance cdx2 hep expression gallbladder adenocarcinomas present study examined expression frequencies cdx2 hepatocyte antigen hep explored clinicopathologic significances gallbladder adenocarcinoma immunohistochemistry used detect compare frequencies cdx2 hep expression 108 samples gallbladder adenocarcinoma 46 peri tumor tissues 35 chronic cholecystitis expression frequencies cdx2 hep 49 108 45 4 45 108 41 7 gallbladder carcinoma 13 46 28 3 11 46 23 9 peri tumor tissues 5 35 14 3 2 35 5 7 chronic cholecystitis positive staining cdx2 hep gallbladder adenocarcinoma significantly higher peritumoral tissues p 0 05 chronic cholecystits p 0 01 expression cdx2 hep negatively correlated grade differentiation tumor size lymph node metastasis p 0 01 p 0 05 elevated expression frequency cdx2 hep associated increased overall survival p 0 003 p 0 002 multivariate cox regression analysis showed cdx2 p 0 014 hep p 0 026 expression independent prognostic predictor gallbladder adenocarcinoma cdx2 hep might function important biological markers development prognosis gallbladder adenocarcinoma stn","probabilities":0.7777778,"Title":"Expression Of Cdx2 And Hepatocyte Antigen In Benign And Malignant Lesions Of Gallbladder And Its Correlation With Histopathologic Type And Clinical Outcome","Abstract":"Recent studies have shown that both CDX2 and Hepatocyte antigen (Hep) are detected in different types of cancer and associated with clinical prognosis. However, fever studies have examined gallbladder cancer specimens, and little is known about the clinicopathological significance of both CDX2 and Hep expression in gallbladder adenocarcinomas. In present study, we examined the expression frequencies of CDX2 and Hepatocyte antigen (Hep), and explored their clinicopathologic significances in gallbladder adenocarcinoma. Immunohistochemistry was used to detect and compare the frequencies of CDX2 and Hep expression in 108 samples of gallbladder adenocarcinoma, 46 peri-tumor tissues and 35 chronic cholecystitis. The expression frequencies for CDX2 and Hep were 49/108 (45.4%) and 45/108 (41.7%) in gallbladder carcinoma; 13/46 (28.3%) and 11/46 (23.9) in peri-tumor tissues; 5/35 (14.3%) and 2/35 (5.7%) in chronic cholecystitis. The positive staining of CDX2 or Hep in gallbladder adenocarcinoma was significantly higher than that in peritumoral tissues (both, P < 0.05), and chronic cholecystits (both, P < 0.01). The expression of CDX2 or Hep was negatively correlated to grade of differentiation, tumor size and lymph node metastasis (P < 0.01 or P < 0.05). Elevated expression frequency of CDX2 or Hep was associated with increased overall survival (P = 0.003 or P = 0.002). Multivariate Cox regression analysis showed that CDX2 (P = 0.014) or Hep (P = 0.026) expression was an independent prognostic predictor in gallbladder adenocarcinoma. CDX2 and Hep might function as important biological markers in the development and prognosis of gallbladder adenocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Expression Of Cdx2 And Hepatocyte Antigen In Benign And Malignant Lesions Of Gallbladder And Its Correlation With Histopathologic Type And Clinical Outcome Recent studies have shown that both CDX2 and Hepatocyte antigen (Hep) are detected in different types of cancer and associated with clinical prognosis. However, fever studies have examined gallbladder cancer specimens, and little is known about the clinicopathological significance of both CDX2 and Hep expression in gallbladder adenocarcinomas. In present study, we examined the expression frequencies of CDX2 and Hepatocyte antigen (Hep), and explored their clinicopathologic significances in gallbladder adenocarcinoma. Immunohistochemistry was used to detect and compare the frequencies of CDX2 and Hep expression in 108 samples of gallbladder adenocarcinoma, 46 peri-tumor tissues and 35 chronic cholecystitis. The expression frequencies for CDX2 and Hep were 49/108 (45.4%) and 45/108 (41.7%) in gallbladder carcinoma; 13/46 (28.3%) and 11/46 (23.9) in peri-tumor tissues; 5/35 (14.3%) and 2/35 (5.7%) in chronic cholecystitis. The positive staining of CDX2 or Hep in gallbladder adenocarcinoma was significantly higher than that in peritumoral tissues (both, P < 0.05), and chronic cholecystits (both, P < 0.01). The expression of CDX2 or Hep was negatively correlated to grade of differentiation, tumor size and lymph node metastasis (P < 0.01 or P < 0.05). Elevated expression frequency of CDX2 or Hep was associated with increased overall survival (P = 0.003 or P = 0.002). Multivariate Cox regression analysis showed that CDX2 (P = 0.014) or Hep (P = 0.026) expression was an independent prognostic predictor in gallbladder adenocarcinoma. CDX2 and Hep might function as important biological markers in the development and prognosis of gallbladder adenocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"ribonucleotide reductase subunit m1 assessed quantitative double fluorescence immunohistochemistry predicts efficacy gemcitabine biliary tract carcinoma gemcitabine commonly used chemotherapeutic agent advanced biliary tract carcinoma btc although efficacy insufficient therefore essential establish new diagnostic methods predict responders treatment aim study identify reliable chemoresistance marker gemcitabine btc among 4 molecules hent1 dck rrm1 rrm2 involved gemcitabine metabolism expression 4 molecules investigated 5 btc cell lines correlated gemcitabine sensitivity rrm1 protein also assessed quantitative double fluorescence immunohistochemistry qdfihc 10 patients unresectable recurrent btc received gemcitabine based chemotherapy rrm1 rrm2 protein strongly correlated ic 50 value gemcitabine btc cell lines r 0 935 0 771 respectively addition patients low rrm1 significantly sensitive gemcitabine p 0 033 survival significantly better patients high rrm1 p 0 001 conclusion rrm1 particularly protein level reliable marker gemcitabine resistance btc furthermore qdfihc useful method assessment rrm1 protein order design tailor made chemotherapeutic regimen btc patients stn","probabilities":0.9467213,"Title":"Ribonucleotide Reductase Subunit M1 Assessed By Quantitative Double-Fluorescence Immunohistochemistry Predicts The Efficacy Of Gemcitabine In Biliary Tract Carcinoma","Abstract":"Gemcitabine is a commonly used chemotherapeutic agent for advanced biliary tract carcinoma (BTC), although its efficacy is insufficient. Therefore, it is essential to establish new diagnostic methods, which can predict responders before the treatment. The aim of this study is to identify the most reliable chemoresistance marker to gemcitabine in BTC among the 4 molecules (hENT1, dCK, RRM1 and RRM2) involved in gemcitabine metabolism. The expression of 4 molecules were investigated in 5 BTC cell lines, and correlated with gemcitabine sensitivity. RRM1 protein was also assessed by quantitative double-fluorescence immunohistochemistry (qDFIHC) in 10 patients with unresectable or recurrent BTC who received gemcitabine-based chemotherapy. RRM1 and RRM2 protein strongly correlated with the IC(50) value for gemcitabine in BTC cell lines (R=0.935, 0.771, respectively). In addition, patients with low RRM1 were significantly more sensitive to gemcitabine (p=0.033), and their survival was significantly better than patients with high RRM1 (p=0.001). In conclusion, RRM1 particularly in protein level is a reliable marker for gemcitabine resistance in BTC. Furthermore, qDFIHC is a useful method for the assessment of RRM1 protein, in order to design a tailor-made chemotherapeutic regimen for BTC patients.","Source":"STN","category":"ANIMAL","training_data":"Ribonucleotide Reductase Subunit M1 Assessed By Quantitative Double-Fluorescence Immunohistochemistry Predicts The Efficacy Of Gemcitabine In Biliary Tract Carcinoma Gemcitabine is a commonly used chemotherapeutic agent for advanced biliary tract carcinoma (BTC), although its efficacy is insufficient. Therefore, it is essential to establish new diagnostic methods, which can predict responders before the treatment. The aim of this study is to identify the most reliable chemoresistance marker to gemcitabine in BTC among the 4 molecules (hENT1, dCK, RRM1 and RRM2) involved in gemcitabine metabolism. The expression of 4 molecules were investigated in 5 BTC cell lines, and correlated with gemcitabine sensitivity. RRM1 protein was also assessed by quantitative double-fluorescence immunohistochemistry (qDFIHC) in 10 patients with unresectable or recurrent BTC who received gemcitabine-based chemotherapy. RRM1 and RRM2 protein strongly correlated with the IC(50) value for gemcitabine in BTC cell lines (R=0.935, 0.771, respectively). In addition, patients with low RRM1 were significantly more sensitive to gemcitabine (p=0.033), and their survival was significantly better than patients with high RRM1 (p=0.001). In conclusion, RRM1 particularly in protein level is a reliable marker for gemcitabine resistance in BTC. Furthermore, qDFIHC is a useful method for the assessment of RRM1 protein, in order to design a tailor-made chemotherapeutic regimen for BTC patients. STN","prediction_labels":"ANIMAL"},{"cleaned":"evaluation positive ductal margins cholangiocarcinoma intraoperative histological examination introduction frozen section analysis remains method con rm microscopic extension cancer ductal resection margins surgery however several reports found prognosis patients positive bile duct stump differ signi cantly carcinoma negative patients reports even described long term survival patients positive surgical bile duct stump study status surgical margins postoperative course evaluated 93 patients extrahepatic bile duct carcinoma elucidate uences remnant carcinoma situ postoperative survival method consecutive patients underwent curative intent resection cholangiocarcinoma institution january 2004 may 2012 identi ed retrospectively collected database evaluated postoperative survival disease free survival performed immunochistochemical staining targeting ki 67 p53 positive margin evaluate relation protein prognosis results divided patients two groups margin positive group negative group major vessel invasion peeled surface margin positive cases signi cantly higher positive group negative group focused positive group divided group two groups according resected margin status carcinoma situ bile duct stump invasive carcinoma surgical margin signi cant differences clinicopathological ndings two groups recurrence survival signi cantly longer cis group invasive group performed immunohistochemical staining targeting p53 ki 67of positive margin statistical relations cis invasive group expression p53 ki 67 moreover statistical relations expression p53 ki 67 survival recurrence conclusions resected margin status important postoperative survival recurrence cholangiocarcinoma google scholar","probabilities":0.9799733,"Title":"Evaluation Of Positive Ductal Margins Of Cholangiocarcinoma In Intraoperative Histological Examination","Abstract":"Introduction: Frozen-section analysis remains the only method to confirm microscopic extension of the cancer at the ductal resection margins during surgery. However, several reports have found that prognosis for patients with a positive bile duct stump does not differ significantly from that of carcinoma-negative patients, and some reports have even described long-term survival of patients with a positive surgical bile duct stump. In this study, status of the surgical margins and postoperative course were evaluated in 93 patients with extrahepatic bile duct carcinoma to elucidate the influences of remnant carcinoma in situ on postoperative survival. Method: All consecutive patients who underwent curative intent resection for a cholangiocarcinoma at our institution between January 2004 and May 2012 were identified from a retrospectively collected database. We evaluated the postoperative survival and disease free survival. We performed immunochistochemical staining targeting Ki 67 and p53 for positive margin to evaluate the relation of these protein and prognosis. Results: We divided these patients into two groups, margin positive group and negative group. The major vessel invasion and peeled surface margin positive cases were significantly higher in positive group than negative group. We focused on positive group and divided this group into two groups according to resected margin status: carcinoma in situ at the bile duct stump and invasive carcinoma at any surgical margin. There were no significant differences in clinicopathological findings between two groups. Recurrence and Survival were significantly longer in CIS group than Invasive group. We performed immunohistochemical staining targeting p53, Ki 67of positive margin. There were no statistical relations between CIS, invasive group and expression of p53 and Ki 67. Moreover there were no statistical relations between the expression of p53 and Ki 67 and survival and recurrence. Conclusions: Resected margin status is the most important to postoperative survival and recurrence in cholangiocarcinoma.","Source":"Google Scholar","category":"ANIMAL","training_data":"Evaluation Of Positive Ductal Margins Of Cholangiocarcinoma In Intraoperative Histological Examination Introduction: Frozen-section analysis remains the only method to confirm microscopic extension of the cancer at the ductal resection margins during surgery. However, several reports have found that prognosis for patients with a positive bile duct stump does not differ significantly from that of carcinoma-negative patients, and some reports have even described long-term survival of patients with a positive surgical bile duct stump. In this study, status of the surgical margins and postoperative course were evaluated in 93 patients with extrahepatic bile duct carcinoma to elucidate the influences of remnant carcinoma in situ on postoperative survival. Method: All consecutive patients who underwent curative intent resection for a cholangiocarcinoma at our institution between January 2004 and May 2012 were identified from a retrospectively collected database. We evaluated the postoperative survival and disease free survival. We performed immunochistochemical staining targeting Ki 67 and p53 for positive margin to evaluate the relation of these protein and prognosis. Results: We divided these patients into two groups, margin positive group and negative group. The major vessel invasion and peeled surface margin positive cases were significantly higher in positive group than negative group. We focused on positive group and divided this group into two groups according to resected margin status: carcinoma in situ at the bile duct stump and invasive carcinoma at any surgical margin. There were no significant differences in clinicopathological findings between two groups. Recurrence and Survival were significantly longer in CIS group than Invasive group. We performed immunohistochemical staining targeting p53, Ki 67of positive margin. There were no statistical relations between CIS, invasive group and expression of p53 and Ki 67. Moreover there were no statistical relations between the expression of p53 and Ki 67 and survival and recurrence. Conclusions: Resected margin status is the most important to postoperative survival and recurrence in cholangiocarcinoma. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"squamous adenosquamous carcinoma gallbladder analysis 34 cases comparison clinicopathologic features surgical outcomes adenocarcinoma objectives explore clinicopathological features effects surgical treatment squamous adenosquamous carcinoma gallbladder methods enrolled 411 patients surgically treated gallbladder cancer hospital including 10 squamous cell carcinoma scc 24 adenosquamous carcinoma asc 377 adenocarcinoma ac asc scc group compared ac group clinicopathological features surgical outcomes results patients average age 61 4 years abdominal pain common presenting symptom 67 6 patients gallstones patients advanced stage t3 t4 carcinomas asc scc group significantly higher percentages t4 disease 61 8 n1 nodal involvement 58 8 ac group t4 disease 34 0 p 0 001 n1 involvement 39 0 p 0 02 patients asc scc group underwent r0 resections significantly better 1 year survival 30 underwent r1 r2 resections 0 p 0 025 lower 1 year survival rates similar staged patients ac group 69 3 p 0 016 conclusions patients gallbladder asc scc similar ac clinical characteristics tended infiltration multiple adjacent organs lymphatic metastasis curative resection give patients better outcomes pubmed","probabilities":0.962963,"Title":"Squamous/adenosquamous carcinoma of the gallbladder: Analysis of 34 cases and comparison of clinicopathologic features and surgical outcomes with adenocarcinoma","Abstract":"OBJECTIVES: To explore clinicopathological features and effects of surgical treatment of squamous/adenosquamous carcinoma of the gallbladder. METHODS: We enrolled 411 patients who were surgically treated for gallbladder cancer in our hospital, including 10 with squamous cell carcinoma (SCC), 24 with adenosquamous carcinoma (ASC), and 377 with adenocarcinoma (AC). The ASC-SCC group was compared with the AC group for clinicopathological features and surgical outcomes. RESULTS: The patients' average age was 61.4 years. Abdominal pain was the most common presenting symptom, and 67.6% of patients had gallstones. All patients had advanced-stage (T3/T4) carcinomas. The ASC-SCC group had significantly higher percentages of T4 disease (61.8%) and N1 nodal involvement (58.8%) than did the AC group (T4 disease: 34.0%, P = 0.001; N1 involvement: 39.0%, P = 0.02). Patients in the ASC-SCC group who underwent R0 resections had significantly better 1-year survival (30%) than those who underwent R1 or R2 resections (0%; P = 0.025), but lower 1-year survival rates than similar-staged patients in the AC group (69.3%; P = 0.016). CONCLUSIONS: Patients with gallbladder ASC-SCC were similar to those with AC in clinical characteristics, but tended to have more infiltration of multiple adjacent organs and lymphatic metastasis. Curative resection could give these patients better outcomes.","Source":"PubMed","category":"HUMAN","training_data":"Squamous/adenosquamous carcinoma of the gallbladder: Analysis of 34 cases and comparison of clinicopathologic features and surgical outcomes with adenocarcinoma OBJECTIVES: To explore clinicopathological features and effects of surgical treatment of squamous/adenosquamous carcinoma of the gallbladder. METHODS: We enrolled 411 patients who were surgically treated for gallbladder cancer in our hospital, including 10 with squamous cell carcinoma (SCC), 24 with adenosquamous carcinoma (ASC), and 377 with adenocarcinoma (AC). The ASC-SCC group was compared with the AC group for clinicopathological features and surgical outcomes. RESULTS: The patients' average age was 61.4 years. Abdominal pain was the most common presenting symptom, and 67.6% of patients had gallstones. All patients had advanced-stage (T3/T4) carcinomas. The ASC-SCC group had significantly higher percentages of T4 disease (61.8%) and N1 nodal involvement (58.8%) than did the AC group (T4 disease: 34.0%, P = 0.001; N1 involvement: 39.0%, P = 0.02). Patients in the ASC-SCC group who underwent R0 resections had significantly better 1-year survival (30%) than those who underwent R1 or R2 resections (0%; P = 0.025), but lower 1-year survival rates than similar-staged patients in the AC group (69.3%; P = 0.016). CONCLUSIONS: Patients with gallbladder ASC-SCC were similar to those with AC in clinical characteristics, but tended to have more infiltration of multiple adjacent organs and lymphatic metastasis. Curative resection could give these patients better outcomes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"biliary tract cancers olmsted county minnesota 1976 2008 objectives epidemiology biliary tract cancers changed united states past several decades aim study evaluate biliary tract cancers regard incidence rates etiology treatment survival olmsted county 1976 2008 methods community residents 20 years age newly diagnosed biliary tract cancers identified using rochester epidemiology project clinical information including tumor stage treatment survival status abstracted medical records incidence rate calculated considering entire population olmsted county risk adjusted age sex according us census 2000 population temporal trends patient survival biliary tract cancers assessed results total 116 subjects met study criteria age sex adjusted incidence rate intrahepatic cholangiocarcinoma icc increased 0 3 2 1 p 0 02 one gall bladder gb cancer decreased 4 0 2 2 p 0 04 per 100 000 person years 1976 2008 p 0 01 overall incidence rates remaining biliary tract cancers changed overall 59 patients presented stage 3 4 cancers median survival 6 3 months survival patients biliary tract cancer minimally improved median survival 4 2 7 7 months 1976 2008 p 0 05 conclusions olmsted county incidence icc gb cancer increased decreased respectively prognosis remains poor community residents diagnosed biliary tract cancers stn","probabilities":0.9799733,"Title":"Biliary Tract Cancers In Olmsted County Minnesota 1976-2008","Abstract":"Objectives: The epidemiology of biliary tract cancers has changed in the United States in the past several decades. The aim of this study is to evaluate biliary tract cancers with regard to the incidence rates, etiology, treatment, and survival in Olmsted County between 1976 and 2008. \r\n\r\n Methods: Community residents over 20 years of age with a newly diagnosed biliary tract cancers were identified using the Rochester Epidemiology Project. Clinical information, including tumor stage, treatment, and survival status was abstracted from the medical records. The incidence rate was calculated considering the entire population of Olmsted County to be at risk and adjusted by age and sex according to US Census 2000 population. Temporal trends of patient survival with biliary tract cancers were assessed. \r\n\r\n Results: A total of 116 subjects met the study criteria. The age-sex-adjusted incidence rate of intrahepatic cholangiocarcinoma (ICC) increased from 0.3 to 2.1 (P=0.02) but one of gall bladder (GB) cancer decreased from 4.0 to 2.2 (P=0.04) per 100,000 person-years between 1976 and 2008 (P<0.01). Overall incidence rates of remaining biliary tract cancers have not changed. Overall 59% of patients presented with stage 3 or 4 cancers and a median survival was 6.3 months. Survival in patients with biliary tract cancer has minimally improved from median survival of 4.2-7.7 months between 1976 and 2008 (P=0.05). \r\n\r\n Conclusions: In Olmsted County, the incidence of ICC and GB cancer has increased and decreased, respectively. The prognosis remains poor in community residents diagnosed with biliary tract cancers.","Source":"STN","category":"HUMAN","training_data":"Biliary Tract Cancers In Olmsted County Minnesota 1976-2008 Objectives: The epidemiology of biliary tract cancers has changed in the United States in the past several decades. The aim of this study is to evaluate biliary tract cancers with regard to the incidence rates, etiology, treatment, and survival in Olmsted County between 1976 and 2008. \r\n\r\n Methods: Community residents over 20 years of age with a newly diagnosed biliary tract cancers were identified using the Rochester Epidemiology Project. Clinical information, including tumor stage, treatment, and survival status was abstracted from the medical records. The incidence rate was calculated considering the entire population of Olmsted County to be at risk and adjusted by age and sex according to US Census 2000 population. Temporal trends of patient survival with biliary tract cancers were assessed. \r\n\r\n Results: A total of 116 subjects met the study criteria. The age-sex-adjusted incidence rate of intrahepatic cholangiocarcinoma (ICC) increased from 0.3 to 2.1 (P=0.02) but one of gall bladder (GB) cancer decreased from 4.0 to 2.2 (P=0.04) per 100,000 person-years between 1976 and 2008 (P<0.01). Overall incidence rates of remaining biliary tract cancers have not changed. Overall 59% of patients presented with stage 3 or 4 cancers and a median survival was 6.3 months. Survival in patients with biliary tract cancer has minimally improved from median survival of 4.2-7.7 months between 1976 and 2008 (P=0.05). \r\n\r\n Conclusions: In Olmsted County, the incidence of ICC and GB cancer has increased and decreased, respectively. The prognosis remains poor in community residents diagnosed with biliary tract cancers. STN","prediction_labels":"HUMAN"},{"cleaned":"cd133 expression cancer cells predicts poor prognosis non mucin producing intrahepatic cholangiocarcinoma background cd133 marker stem cells well cancer stem cells study investigated association cd133 expression cancer cells clinical outcome non mucin producing intrahepatic cholangiocarcinoma icc methods fifty seven non mucin producing icc patients enrolled study immunohistochemistry ihc immunofluorescence staining cd133 well cancer associated proteins including cytokeratin 19 tgf 1 p smad2 epithelial mesenchymal transition emt markers s100a4 e cadherin vimentin analyzed results ihc staining showed tumor cells 52 6 patients expressed cd133 cd133 patients significantly higher metastasis rate without cd133 tumor cells 36 7 vs 10 1 p 0 03 cd133 patients shorter overall disease free survival time compared cd133 patients furthermore 90 9 cd133 patients developed cancer recurrence compared 64 3 cd133 patients p 0 02 compared cd133 patients tumor cells cd133 patients demonstrated high levels tgf p smad2 well emt like alteration characterized loss e cadherin expression vimentin s100a4 conclusions cd133 expression icc tumor cells indicates poor prognosis disease might associated tgf related emt alterations stn","probabilities":0.9799733,"Title":"Cd133 Expression In Cancer Cells Predicts Poor Prognosis Of Non-Mucin Producing Intrahepatic Cholangiocarcinoma","Abstract":"Background: CD133 is a marker of stem cells as well cancer stem cells. This study investigated the association between CD133 expression in cancer cells and the clinical outcome of non-mucin producing intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: Fifty-seven non-mucin producing ICC patients were enrolled in this study. Immunohistochemistry (IHC) and immunofluorescence staining for CD133 as well as other cancer-associated proteins, including cytokeratin 19, TGF-β1, p-Smad2 and epithelial-mesenchymal transition (EMT) markers S100A4, E-Cadherin and Vimentin were analyzed. \r\n\r\n Results: IHC staining showed that tumor cells in 52.6% of patients expressed CD133. The CD133+ patients had significantly higher metastasis rate than those without CD133+ tumor cells (36.7% vs. 10.1%, p = 0.03). The CD133+ patients had shorter overall and disease-free survival time as compared to the CD133- patients. Furthermore, 90.9% of CD133+ patients developed cancer recurrence, as compared to 64.3% of CD133- patients (p = 0.02). As compared to CD133- patients, tumor cells in CD133+ patients demonstrated high levels of TGF-β/p-Smad2 as well as EMT-like alteration, characterized by loss of E-Cadherin and expression of Vimentin and S100A4. \r\n\r\n Conclusions: CD133 expression in ICC tumor cells indicates poor prognosis of the disease and might be associated with TGF-β related EMT alterations.","Source":"STN","category":"HUMAN","training_data":"Cd133 Expression In Cancer Cells Predicts Poor Prognosis Of Non-Mucin Producing Intrahepatic Cholangiocarcinoma Background: CD133 is a marker of stem cells as well cancer stem cells. This study investigated the association between CD133 expression in cancer cells and the clinical outcome of non-mucin producing intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Methods: Fifty-seven non-mucin producing ICC patients were enrolled in this study. Immunohistochemistry (IHC) and immunofluorescence staining for CD133 as well as other cancer-associated proteins, including cytokeratin 19, TGF-β1, p-Smad2 and epithelial-mesenchymal transition (EMT) markers S100A4, E-Cadherin and Vimentin were analyzed. \r\n\r\n Results: IHC staining showed that tumor cells in 52.6% of patients expressed CD133. The CD133+ patients had significantly higher metastasis rate than those without CD133+ tumor cells (36.7% vs. 10.1%, p = 0.03). The CD133+ patients had shorter overall and disease-free survival time as compared to the CD133- patients. Furthermore, 90.9% of CD133+ patients developed cancer recurrence, as compared to 64.3% of CD133- patients (p = 0.02). As compared to CD133- patients, tumor cells in CD133+ patients demonstrated high levels of TGF-β/p-Smad2 as well as EMT-like alteration, characterized by loss of E-Cadherin and expression of Vimentin and S100A4. \r\n\r\n Conclusions: CD133 expression in ICC tumor cells indicates poor prognosis of the disease and might be associated with TGF-β related EMT alterations. STN","prediction_labels":"HUMAN"},{"cleaned":"impact preoperative body compositions survival following resection biliary tract cancer background although surgical resection potentially curative treatment biliary tract cancer prognosis remains poor major operation pancreatoduodenectomy hepatectomy aimed investigate impact preoperative body compositions long term survival patients undergoing resection biliary tract cancer methods analysed data patients diagnosed biliary tract cancer underwent surgery 2009 2015 skeletal muscle area skeletal muscle radiation attenuation visceral subcutaneous adipose tissue areas measured computed tomography images l3 vertebral levels obtained resection cancer patients divided two groups based sex specific median values parameter long term survival compared groups results total 371 patients women 39 6 mean age 66 2 9 6 years finally included analysis patients low skeletal muscle index smi significantly shorter median survival high smi 29 vs 39 months p 0 026 patients low skeletal muscle attenuation sma also showed reduced survival compared high sma median survival 25 vs 60 months p 0 002 combining two factors survival highest high smi high sma group reference lowest low smi low sma group hazard ratio 2 18 95 confidence interval 1 44 3 30 visceral subcutaneous adipose tissue areas associated long term survival conclusions low smi low sma computed tomography scan negative impact survival resection biliary tract cancer used preoperative risk assessment assist treatment decision making stn","probabilities":0.7966102,"Title":"Impact Of Preoperative Body Compositions On Survival Following Resection Of Biliary Tract Cancer","Abstract":"Background: Although surgical resection is the only potentially curative treatment for biliary tract cancer, the prognosis remains poor after a major operation such as pancreatoduodenectomy or hepatectomy. We aimed to investigate the impact of preoperative body compositions on long-term survival of patients undergoing resection of biliary tract cancer. \r\n\r\n Methods: We analysed data of patients diagnosed with biliary tract cancer who underwent surgery from 2009 to 2015. Skeletal muscle area, skeletal muscle radiation attenuation, and visceral and subcutaneous adipose tissue areas were measured from the computed tomography images at L3 vertebral levels obtained before resection of cancer. Patients were divided into two groups based on the sex-specific median values for each parameter, and long-term survival was compared between the groups. \r\n\r\n Results: A total of 371 patients (women, 39.6%; mean age, 66.2 ± 9.6 years) were finally included in the analysis. Patients with low skeletal muscle index (SMI) had significantly shorter median survival than those with high SMI (29 vs. 39 months; P = 0.026). Patients with low skeletal muscle attenuation (SMA) also showed reduced survival compared with those with high SMA (median survival 25 vs. 60 months; P = 0.002). Combining these two factors, survival was highest in the high SMI/high SMA group (reference) and lowest in the low SMI/low SMA group (hazard ratio, 2.18; 95% confidence interval, 1.44-3.30). Visceral and subcutaneous adipose tissue areas were not associated with long-term survival. \r\n\r\n Conclusions: Low SMI and low SMA on computed tomography scan have a negative impact on survival after resection of biliary tract cancer. They can be used in preoperative risk assessment to assist in treatment decision making.","Source":"STN","category":"HUMAN","training_data":"Impact Of Preoperative Body Compositions On Survival Following Resection Of Biliary Tract Cancer Background: Although surgical resection is the only potentially curative treatment for biliary tract cancer, the prognosis remains poor after a major operation such as pancreatoduodenectomy or hepatectomy. We aimed to investigate the impact of preoperative body compositions on long-term survival of patients undergoing resection of biliary tract cancer. \r\n\r\n Methods: We analysed data of patients diagnosed with biliary tract cancer who underwent surgery from 2009 to 2015. Skeletal muscle area, skeletal muscle radiation attenuation, and visceral and subcutaneous adipose tissue areas were measured from the computed tomography images at L3 vertebral levels obtained before resection of cancer. Patients were divided into two groups based on the sex-specific median values for each parameter, and long-term survival was compared between the groups. \r\n\r\n Results: A total of 371 patients (women, 39.6%; mean age, 66.2 ± 9.6 years) were finally included in the analysis. Patients with low skeletal muscle index (SMI) had significantly shorter median survival than those with high SMI (29 vs. 39 months; P = 0.026). Patients with low skeletal muscle attenuation (SMA) also showed reduced survival compared with those with high SMA (median survival 25 vs. 60 months; P = 0.002). Combining these two factors, survival was highest in the high SMI/high SMA group (reference) and lowest in the low SMI/low SMA group (hazard ratio, 2.18; 95% confidence interval, 1.44-3.30). Visceral and subcutaneous adipose tissue areas were not associated with long-term survival. \r\n\r\n Conclusions: Low SMI and low SMA on computed tomography scan have a negative impact on survival after resection of biliary tract cancer. They can be used in preoperative risk assessment to assist in treatment decision making. STN","prediction_labels":"HUMAN"},{"cleaned":"low skeletal muscle density associated early death patients suspected perihilar cholangiocarcinoma background low skeletal muscle mass associated increased postoperative morbidity worse survival following resection perihilar cholangiocarcinoma phc investigated predictive value skeletal muscle mass density overall survival os patients suspected phc regardless treatment methods baseline characteristics parameters regarding disease treatment collected patients phc 2002 2014 skeletal muscle mass density measured level third lumbar vertebra ct association skeletal muscle mass density os investigated using kaplan meier method cox survival results median os 233 included patients differ without low skeletal muscle mass p 0 203 whereas significantly different median os months observed patients low hr 7 0 95 ci 4 7 9 3 high hr 12 1 95 ci 8 1 16 1 skeletal muscle density p 0 004 low skeletal muscle density independently associated decreased os hr 1 78 95 ci 1 03 3 07 p 0 040 within first 6 months 6 months hr 0 68 95 ci 0 44 1 07 p 0 093 adjusting age tumour size suspected peritoneal distant metastases imaging conclusion time dependent effect skeletal muscle density os found patients phc regardless subsequent treatment low skeletal muscle density may identify patients risk early death stn","probabilities":0.9799733,"Title":"Low Skeletal Muscle Density Is Associated With Early Death In Patients With Suspected Perihilar Cholangiocarcinoma","Abstract":"Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. \r\n\r\n Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. \r\n\r\n Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. \r\n\r\n Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.","Source":"STN","category":"HUMAN","training_data":"Low Skeletal Muscle Density Is Associated With Early Death In Patients With Suspected Perihilar Cholangiocarcinoma Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. \r\n\r\n Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. \r\n\r\n Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. \r\n\r\n Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death. STN","prediction_labels":"HUMAN"},{"cleaned":"retrospective analysis comparing treatment outcomes gemcitabine 1 combination therapy gemcitabine cisplatin combination therapy patients advanced biliary tract cancer abstract available google scholar","probabilities":0.9799733,"Title":"A Retrospective Analysis Comparing The Treatment Outcomes Of Gemcitabine And S-1 Combination Therapy To Gemcitabine And Cisplatin Combination Therapy In Patients With Advanced Biliary Tract Cancer","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"A Retrospective Analysis Comparing The Treatment Outcomes Of Gemcitabine And S-1 Combination Therapy To Gemcitabine And Cisplatin Combination Therapy In Patients With Advanced Biliary Tract Cancer Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"two major lymphatic pathways gallbladder para aortic lymph nodes dvd purpose photographic review actual dissections compiled demonstrate various lymphatic pathways relationships surrounding structures facilitate development qol surgical procedures methods purpose demonstration three male adult specimens prepared 10 formaldehyde solution injected femoral artery preserved 60 alcohol solution used dissection carried typical fashion without use dyes microscope dissection results recorded sketches photographs video recording results two major lymphatic pathways gallbladder demonstrated left oblique pathway celiac nodes b right descending pathway superior retropancreaticoduodenal node rouvi re third minor pathway superior mesenteric nodes suggested conclusions three pathways finally reach para aortic lumbar lymph nodes importance interaorticocaval nodes level left renal vein emphasized particular significance nodes right descending pathway viewpoint surgical treatment cancer gallbladder pancreas head stn","probabilities":0.9799733,"Title":"Two Major Lymphatic Pathways From The Gallbladder To The Para-Aortic Lymph Nodes (Dvd)","Abstract":"Purpose: This photographic review of actual dissections was compiled to demonstrate the various lymphatic pathways and their relationships to the surrounding structures to facilitate the development of QOL surgical procedures. \r\n\r\n Methods: For the purpose of demonstration, three male adult specimens, prepared with 10% formaldehyde solution injected through the femoral artery and preserved in 60% alcohol solution, were used. Dissection was carried out in typical fashion without the use of dyes or a microscope. The dissection results were recorded in sketches, photographs and video recording. \r\n\r\n Results: Two major lymphatic pathways from the gallbladder are demonstrated: (a) the left oblique pathway to the celiac nodes, and (b) the right descending pathway to the superior retropancreaticoduodenal node (Rouvière). A third and minor pathway to the superior mesenteric nodes is suggested. \r\n\r\n Conclusions: These three pathways finally reach the para-aortic (lumbar) lymph nodes. The importance of the interaorticocaval nodes at the level of the left renal vein should be emphasized, in particular the significance of the nodes of the right descending pathway, from the viewpoint of surgical treatment of cancer of the gallbladder and the pancreas head.","Source":"STN","category":"ANIMAL","training_data":"Two Major Lymphatic Pathways From The Gallbladder To The Para-Aortic Lymph Nodes (Dvd) Purpose: This photographic review of actual dissections was compiled to demonstrate the various lymphatic pathways and their relationships to the surrounding structures to facilitate the development of QOL surgical procedures. \r\n\r\n Methods: For the purpose of demonstration, three male adult specimens, prepared with 10% formaldehyde solution injected through the femoral artery and preserved in 60% alcohol solution, were used. Dissection was carried out in typical fashion without the use of dyes or a microscope. The dissection results were recorded in sketches, photographs and video recording. \r\n\r\n Results: Two major lymphatic pathways from the gallbladder are demonstrated: (a) the left oblique pathway to the celiac nodes, and (b) the right descending pathway to the superior retropancreaticoduodenal node (Rouvière). A third and minor pathway to the superior mesenteric nodes is suggested. \r\n\r\n Conclusions: These three pathways finally reach the para-aortic (lumbar) lymph nodes. The importance of the interaorticocaval nodes at the level of the left renal vein should be emphasized, in particular the significance of the nodes of the right descending pathway, from the viewpoint of surgical treatment of cancer of the gallbladder and the pancreas head. STN","prediction_labels":"HUMAN"},{"cleaned":"efficacy adjuvant chemotherapy prognostic factors patients extrahepatic bile duct cancer background surgical resection curative treatment extrahepatic bile duct cancer additionally recurrence rate curative surgery relatively high requiring adjuvant therapy however efficacy adjuvant chemotherapy compared surgery alone yet clarified study aimed evaluate efficacy adjuvant chemotherapy identify prognostic factors influencing survival extrahepatic bile duct cancer patients underwent curative surgical resection methods ninety seven patients extrahepatic bile duct cancer underwent curative resection january 2005 december 2010 retrospectively analyzed results among 97 patients 31 underwent adjuvant chemotherapy 66 5 year overall survival rate 34 patients underwent adjuvant chemotherapy significant difference overall survival patients underwent adjuvant chemotherapy p 0 228 multivariate analysis postoperative carbohydrate antigen 19 9 levels histologic grade independent prognostic factors related long term survival p 0 05 conclusions postoperative adjuvant chemotherapy improve survival surgical resection extrahepatic bile duct cancer pubmed","probabilities":0.9799733,"Title":"Efficacy of Adjuvant Chemotherapy and Prognostic Factors for Patients with Extrahepatic Bile Duct Cancer","Abstract":"BACKGROUND: Surgical resection is the only curative treatment for extrahepatic bile duct cancer. Additionally, the recurrence rate after curative surgery is relatively high, requiring adjuvant therapy. However, the efficacy of adjuvant chemotherapy compared with surgery alone has not yet been clarified. This study aimed to evaluate the efficacy of adjuvant chemotherapy and identify prognostic factors influencing survival in extrahepatic bile duct cancer patients who underwent curative surgical resection. METHODS: Ninety-seven patients with extrahepatic bile duct cancer who underwent curative resection between January 2005 and December 2010 were retrospectively analyzed. RESULTS: Among the 97 patients, 31 underwent adjuvant chemotherapy and 66 did not. The 5-year overall survival rate was 34% for patients who underwent adjuvant chemotherapy. There was no significant difference for overall survival between patients who underwent adjuvant chemotherapy and those who did not (p = 0.228). On multivariate analysis, postoperative carbohydrate antigen 19-9 levels and histologic grade were independent prognostic factors related to long-term survival (p < 0.05). CONCLUSIONS: Postoperative adjuvant chemotherapy did not improve survival after surgical resection for extrahepatic bile duct cancer.","Source":"PubMed","category":"HUMAN","training_data":"Efficacy of Adjuvant Chemotherapy and Prognostic Factors for Patients with Extrahepatic Bile Duct Cancer BACKGROUND: Surgical resection is the only curative treatment for extrahepatic bile duct cancer. Additionally, the recurrence rate after curative surgery is relatively high, requiring adjuvant therapy. However, the efficacy of adjuvant chemotherapy compared with surgery alone has not yet been clarified. This study aimed to evaluate the efficacy of adjuvant chemotherapy and identify prognostic factors influencing survival in extrahepatic bile duct cancer patients who underwent curative surgical resection. METHODS: Ninety-seven patients with extrahepatic bile duct cancer who underwent curative resection between January 2005 and December 2010 were retrospectively analyzed. RESULTS: Among the 97 patients, 31 underwent adjuvant chemotherapy and 66 did not. The 5-year overall survival rate was 34% for patients who underwent adjuvant chemotherapy. There was no significant difference for overall survival between patients who underwent adjuvant chemotherapy and those who did not (p = 0.228). On multivariate analysis, postoperative carbohydrate antigen 19-9 levels and histologic grade were independent prognostic factors related to long-term survival (p < 0.05). CONCLUSIONS: Postoperative adjuvant chemotherapy did not improve survival after surgical resection for extrahepatic bile duct cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"elevation ca19 9 cea associated poor prognosis patients resectable gallbladder carcinoma aims aim study determine whether combination tumour markers carcinoembryonic cea carbohydrate antigen 19 9 ca19 9 helpful predicting prognosis patients gallbladder carcinoma gbc underwent resection methods retrospective analysis clinico pathological features survival 390 patients gbc treated january 2003 december 2013 time dependent receiver operating characteristic roc used evaluate prognostic ability tumour markers combinations preoperative cea ca19 9 tested potential prognostic factors results evaluation preoperative cea ca19 9 showed patients tumour markers within normal range best prognosis median survival 27 months r0 rate 86 patients tumour markers elevated poorest prognosis lower r0 rate p 0 001 combination cea ca19 9 independent risk factor overall survival auroc 5 years combination cea ca19 9 0 798 similar cea 0 765 ca19 9 0 771 alone p 0 103 p 0 147 conclusions combination elevated preoperative cea ca19 9 associated worse prognosis patients gbc underwent resection pubmed","probabilities":0.9799733,"Title":"Elevation of CA19-9 and CEA is associated with a poor prognosis in patients with resectable gallbladder carcinoma","Abstract":"AIMS: The aim of this study was to determine whether a combination of the tumour markers carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA19-9) would be helpful in predicting the prognosis of patients with gallbladder carcinoma (GBC) who underwent resection. METHODS: A retrospective analysis of clinico-pathological features and survival of 390 patients with GBC who were treated between January 2003 and December 2013. Time-dependent receiver operating characteristic (ROC) was used to evaluate the prognostic ability of tumour markers. Combinations of preoperative CEA and CA19-9 were tested as potential prognostic factors. RESULTS: The evaluation of preoperative CEA and CA19-9 showed that patients with both tumour markers within the normal range had the best prognosis with a median survival of 27 months and R0 rate of 86%. Patients with both tumour markers elevated had the poorest prognosis and lower R0 rate (p < 0.001). The combination of CEA and CA19-9 was an independent risk factor for overall survival. The AUROC at 5 years of combination of CEA and CA19-9 was 0.798, which was similar to CEA (0.765) or CA19-9 (0.771) alone (p = 0.103, p = 0.147). CONCLUSIONS: A combination of an elevated preoperative CEA and CA19-9 was associated with a worse prognosis for patients with GBC who underwent resection.","Source":"PubMed","category":"HUMAN","training_data":"Elevation of CA19-9 and CEA is associated with a poor prognosis in patients with resectable gallbladder carcinoma AIMS: The aim of this study was to determine whether a combination of the tumour markers carcinoembryonic (CEA) and carbohydrate antigen 19-9 (CA19-9) would be helpful in predicting the prognosis of patients with gallbladder carcinoma (GBC) who underwent resection. METHODS: A retrospective analysis of clinico-pathological features and survival of 390 patients with GBC who were treated between January 2003 and December 2013. Time-dependent receiver operating characteristic (ROC) was used to evaluate the prognostic ability of tumour markers. Combinations of preoperative CEA and CA19-9 were tested as potential prognostic factors. RESULTS: The evaluation of preoperative CEA and CA19-9 showed that patients with both tumour markers within the normal range had the best prognosis with a median survival of 27 months and R0 rate of 86%. Patients with both tumour markers elevated had the poorest prognosis and lower R0 rate (p < 0.001). The combination of CEA and CA19-9 was an independent risk factor for overall survival. The AUROC at 5 years of combination of CEA and CA19-9 was 0.798, which was similar to CEA (0.765) or CA19-9 (0.771) alone (p = 0.103, p = 0.147). CONCLUSIONS: A combination of an elevated preoperative CEA and CA19-9 was associated with a worse prognosis for patients with GBC who underwent resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect adjuvant chemotherapy resectable cholangiocarcinoma meta analysis systematic review background benefit adjuvant chemotherapy resectable cholangiocarcinoma remains unclear due lack randomized control studies study aimed investigate possible benefit postoperative adjuvant chemotherapy resectable cholangiocarcinoma data sources relevant research articles published 1st march 2018 pubmed embase cochrane library databases retrieved published data extracted analyzed revman 5 3 results presented hazard ratios hrs 95 confidence intervals ci forest plots results one prospective eighteen retrospective studies included total number 11 458 patients 4696 received postoperative chemotherapy significant improvement overall survival os patients underwent operation adjuvant chemotherapy compared underwent operation alone hr 0 61 p 0 001 subgroup analyses show postoperative chemotherapy group compared operation alone group indicated follows hilar cholangiocarcinoma group hr 0 60 p 0 001 intrahepatic cholangiocarcinoma group hr 0 60 p 0 001 r1 resection group hr 0 71 p 0 04 ln positive diagnosis group hr 0 58 p 0 001 gemcitabine based chemotherapy group hr 0 42 p 0 001 distal cholangiocarcinoma group hr 0 48 p 0 17 r0 resection group hr 0 69 p 0 43 5 flurouracil based chemotherapy group hr 0 90 p 0 66 respectively conclusions postoperative adjuvant chemotherapy improve os intrahepatic hilar cholangiocarcinoma patients however distal cholangiocarcinoma patients gain benefit postoperative adjuvant chemotherapy prospective randomized trials warranted order define standard chemotherapy regimen pubmed","probabilities":0.9799733,"Title":"The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review","Abstract":"BACKGROUND: The benefit of adjuvant chemotherapy for resectable cholangiocarcinoma remains unclear due to the lack of randomized control studies. This study aimed to investigate the possible benefit of postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. DATA SOURCES: Relevant research articles published before 1st March 2018 in PubMed, Embase and the Cochrane library databases were retrieved. Published data were extracted and analyzed by RevMan 5.3, and the results were presented as hazard ratios (HRs) [95% confidence intervals (CI)] and forest plots. RESULTS: One prospective and eighteen retrospective studies were included, with a total number of 11,458 patients, 4696 of whom received postoperative chemotherapy. There was a significant improvement of the overall survival (OS) for patients who underwent operation + adjuvant chemotherapy compared to those who underwent operation alone (HR = 0.61; P < 0.001). Subgroup analyses show that the postoperative chemotherapy group compared with operation alone group are indicated as follows: hilar cholangiocarcinoma group (HR = 0.60; P < 0.001), intrahepatic cholangiocarcinoma group (HR = 0.60; P < 0.001), R1 resection group (HR = 0.71; P = 0.04), LN-positive diagnosis group (HR = 0.58; P < 0.001), gemcitabine-based chemotherapy group (HR = 0.42; P < 0.001), distal cholangiocarcinoma group (HR = 0.48; P = 0.17), R0 resection group (HR = 0.69; P = 0.43), and 5-flurouracil-based chemotherapy group (HR = 0.90; P = 0.66), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy can improve the OS in intrahepatic and hilar cholangiocarcinoma patients. However, distal cholangiocarcinoma patients gain no benefit from postoperative adjuvant chemotherapy. Prospective randomized trials are warranted in order to define the standard chemotherapy regimen.","Source":"PubMed","category":"HUMAN","training_data":"The effect of adjuvant chemotherapy in resectable cholangiocarcinoma: A meta-analysis and systematic review BACKGROUND: The benefit of adjuvant chemotherapy for resectable cholangiocarcinoma remains unclear due to the lack of randomized control studies. This study aimed to investigate the possible benefit of postoperative adjuvant chemotherapy for resectable cholangiocarcinoma. DATA SOURCES: Relevant research articles published before 1st March 2018 in PubMed, Embase and the Cochrane library databases were retrieved. Published data were extracted and analyzed by RevMan 5.3, and the results were presented as hazard ratios (HRs) [95% confidence intervals (CI)] and forest plots. RESULTS: One prospective and eighteen retrospective studies were included, with a total number of 11,458 patients, 4696 of whom received postoperative chemotherapy. There was a significant improvement of the overall survival (OS) for patients who underwent operation + adjuvant chemotherapy compared to those who underwent operation alone (HR = 0.61; P < 0.001). Subgroup analyses show that the postoperative chemotherapy group compared with operation alone group are indicated as follows: hilar cholangiocarcinoma group (HR = 0.60; P < 0.001), intrahepatic cholangiocarcinoma group (HR = 0.60; P < 0.001), R1 resection group (HR = 0.71; P = 0.04), LN-positive diagnosis group (HR = 0.58; P < 0.001), gemcitabine-based chemotherapy group (HR = 0.42; P < 0.001), distal cholangiocarcinoma group (HR = 0.48; P = 0.17), R0 resection group (HR = 0.69; P = 0.43), and 5-flurouracil-based chemotherapy group (HR = 0.90; P = 0.66), respectively. CONCLUSIONS: Postoperative adjuvant chemotherapy can improve the OS in intrahepatic and hilar cholangiocarcinoma patients. However, distal cholangiocarcinoma patients gain no benefit from postoperative adjuvant chemotherapy. Prospective randomized trials are warranted in order to define the standard chemotherapy regimen. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison general obesity measures body fat distribution older adults relation cancer risk meta analysis individual participant data seven prospective cohorts europe background evaluated associations anthropometric indicators general obesity body mass index bmi established risk factor various cancer body fat distribution waist circumference wc hip circumference hc waist hip ratio whr may better reflect metabolic complications obesity total obesity related site specific colorectal postmenopausal breast cancer incidence methods meta analysis seven prospective cohort studies participating chances consortium including 18 668 men 24 751 women mean age 62 63 years respectively harmonised individual participant data seven cohorts analysed separately alternatively anthropometric indicator using multivariable cox proportional hazards models results median follow period 12 years 1656 first incident obesity related cancers defined postmenopausal female breast colorectum lower oesophagus cardia stomach liver gallbladder pancreas endometrium ovary kidney occurred men women meta analysis studies associations indicators adiposity per d increment risk obesity related cancers combined yielded following summary hazard ratios 1 11 95 ci 1 02 1 21 bmi 1 13 95 ci 1 04 1 23 wc 1 09 95 ci 0 98 1 21 hc 1 15 95 ci 1 00 1 32 whr increases risk colorectal cancer 16 21 15 20 respectively per d bmi wc hc whr effect modification hormone therapy ht use observed postmenopausal breast cancer p interaction 0 001 never ht users showed 20 increased risk per d bmi wc hc compared ever users conclusions bmi wc hc whr show comparable positive associations obesity related cancers combined colorectal cancer older adults postmenopausal breast cancer report evidence effect modification ht use pubmed","probabilities":0.9799733,"Title":"Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe","Abstract":"BACKGROUND: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. METHODS: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models. RESULTS: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (P(interaction)<0.001), where never HT users showed an ∼20% increased risk per s.d. of BMI, WC, and HC compared to ever users. CONCLUSIONS: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modification by HT use.","Source":"PubMed","category":"HUMAN","training_data":"Comparison of general obesity and measures of body fat distribution in older adults in relation to cancer risk: meta-analysis of individual participant data of seven prospective cohorts in Europe BACKGROUND: We evaluated the associations of anthropometric indicators of general obesity (body mass index, BMI), an established risk factor of various cancer, and body fat distribution (waist circumference, WC; hip circumference, HC; and waist-to-hip ratio, WHR), which may better reflect metabolic complications of obesity, with total obesity-related and site-specific (colorectal and postmenopausal breast) cancer incidence. METHODS: This is a meta-analysis of seven prospective cohort studies participating in the CHANCES consortium including 18 668 men and 24 751 women with a mean age of 62 and 63 years, respectively. Harmonised individual participant data from all seven cohorts were analysed separately and alternatively for each anthropometric indicator using multivariable Cox proportional hazards models. RESULTS: After a median follow-up period of 12 years, 1656 first-incident obesity-related cancers (defined as postmenopausal female breast, colorectum, lower oesophagus, cardia stomach, liver, gallbladder, pancreas, endometrium, ovary, and kidney) had occurred in men and women. In the meta-analysis of all studies, associations between indicators of adiposity, per s.d. increment, and risk for all obesity-related cancers combined yielded the following summary hazard ratios: 1.11 (95% CI 1.02-1.21) for BMI, 1.13 (95% CI 1.04-1.23) for WC, 1.09 (95% CI 0.98-1.21) for HC, and 1.15 (95% CI 1.00-1.32) for WHR. Increases in risk for colorectal cancer were 16%, 21%, 15%, and 20%, respectively per s.d. of BMI, WC, HC, and WHR. Effect modification by hormone therapy (HT) use was observed for postmenopausal breast cancer (P(interaction)<0.001), where never HT users showed an ∼20% increased risk per s.d. of BMI, WC, and HC compared to ever users. CONCLUSIONS: BMI, WC, HC, and WHR show comparable positive associations with obesity-related cancers combined and with colorectal cancer in older adults. For postmenopausal breast cancer we report evidence for effect modification by HT use. PubMed","prediction_labels":"HUMAN"},{"cleaned":"anticancer effect radix astragali cholangiocarcinoma vitro mechanism via network pharmacology background study used network pharmacology method cell model assess e ects radix astragali ra cholangiocarcinoma cca predict core targets molecular mechanisms material methods performed vitro study assess effect ra cca using cck8 assay live cell analysis system trypan blue staining components targets ra analyzed using traditional chinese medicine systems pharmacology database genes associated cca retrieved genecards omim platforms protein protein interactions analyzed string platform components targets disease network built cytoscape timer database revealed expression core targets diverse immune infiltration levels go kegg analyses performed identify molecular biology processes signaling pathways predictions verified western blotting results concentration dependent antitumor activity confirmed cholangiocarcinoma qbc939 cell line treated ra ra contained 16 active compounds quercetin kaempferol core compounds important biotargets ra cca caspase 3 mapk8 myc egfr parp timer database revealed expression caspase3 myc related diverse immune infiltration levels cca results western blotting showed ra significantly influenced expression 5 targets network pharmacology predicted conclusions ra active medicinal material developed safe effective multi targeted anticancer treatment cca stn","probabilities":0.9467213,"Title":"Anticancer Effect Of Radix Astragali On Cholangiocarcinoma In Vitro And Its Mechanism Via Network Pharmacology","Abstract":"BACKGROUND This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms. MATERIAL AND METHODS We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed with the STRING platform. The components-targets-disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting. RESULTS Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA. The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted. CONCLUSIONS RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA.","Source":"STN","category":"ANIMAL","training_data":"Anticancer Effect Of Radix Astragali On Cholangiocarcinoma In Vitro And Its Mechanism Via Network Pharmacology BACKGROUND This study used network pharmacology method and cell model to assess the effects of Radix Astragali (RA) on cholangiocarcinoma (CCA) and to predict core targets and molecular mechanisms. MATERIAL AND METHODS We performed an in vitro study to assess the effect of RA on CCA using CCK8 assay, the Live-Cell Analysis System, and trypan blue staining. The components and targets of RA were analyzed using the Traditional Chinese Medicine Systems Pharmacology database, and genes associated with CCA were retrieved from the GeneCards and OMIM platforms. Protein-protein interactions were analyzed with the STRING platform. The components-targets-disease network was built by Cytoscape. The TIMER database revealed the expression of core targets with diverse immune infiltration levels. GO and KEGG analyses were performed to identify molecular-biology processes and signaling pathways. The predictions were verified by Western blotting. RESULTS Concentration-dependent antitumor activity was confirmed in the cholangiocarcinoma QBC939 cell line treated with RA. RA contained 16 active compounds, with quercetin and kaempferol as the core compounds. The most important biotargets for RA in CCA were caspase 3, MAPK8, MYC, EGFR, and PARP. The TIMER database revealed that the expression of caspase3 and MYC was related with diverse immune infiltration levels of CCA. The results of Western blotting showed RA significantly influenced the expression of the 5 targets that network pharmacology predicted. CONCLUSIONS RA is an active medicinal material that can be developed into a safe and effective multi-targeted anticancer treatment for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"eudesmol induces expression apoptosis pathway proteins cholangiocarcinoma cell lines background cholangiocarcinoma cca neglected disease prevalent developing countries high burden mortality rate effective treatment aimed investigate eudesmol molecular target action human cca cell lines using selected key molecules apoptotic pathways materials methods two cca cell lines huh28 hucct1 assessed different time points eudesmol treatment mrna protein expression profiles caspase 3 8 9 p53 p21 bcl 2 bax real time polymerase chain reaction western blot respectively results eudesmol induced expressions p21 p53 mrna protein level huh28 hucct1 cells cca cells also expressed caspase 3 8 9 bax mrna protein level among others eudesmol treatment indicating role intrinsic extrinsic caspase dependent apoptotic pathways conclusion study demonstrated eudesmol induced expression apoptosis pathway proteins suggesting potential role promoting caspase dependent apoptotic pathway induction cell cycle arrest cca cell lines eudesmol considered potential compound investigation anti cca agent stn","probabilities":0.9467213,"Title":"ß-Eudesmol Induces The Expression Of Apoptosis Pathway Proteins In Cholangiocarcinoma Cell Lines","Abstract":"Background: Cholangiocarcinoma (CCA) is a neglected disease prevalent in developing countries with high burden and mortality rate, and there is no effective treatment. We aimed to investigate β-eudesmol molecular target of action in human CCA cell lines using the selected key molecules of apoptotic pathways. \r\n\r\n Materials and methods: Two CCA cell lines (HuH28 and HuCCT1) were assessed at different time points after β-eudesmol treatment for mRNA and protein expression profiles of caspase-3, -8, -9, p53, p21, Bcl-2, and Bax by real-time polymerase chain reaction and western blot, respectively. \r\n\r\n Results: β-eudesmol induced expressions of p21 and p53 in mRNA/protein level in HuH28 and HuCCT1 cells. These CCA cells also expressed caspase-3, -8, -9 and bax (mRNA and/or protein level) among others after β-eudesmol treatment indicating its role in both intrinsic and extrinsic caspase-dependent apoptotic pathways. \r\n\r\n Conclusion: The study demonstrated that β-eudesmol induced the expression of apoptosis pathway proteins, suggesting its potential role in promoting the caspase-dependent apoptotic pathway, and induction of the cell cycle arrest in CCA cell lines. β-eudesmol can be considered as a potential compound for further investigation as an anti-CCA agent.","Source":"STN","category":"ANIMAL","training_data":"ß-Eudesmol Induces The Expression Of Apoptosis Pathway Proteins In Cholangiocarcinoma Cell Lines Background: Cholangiocarcinoma (CCA) is a neglected disease prevalent in developing countries with high burden and mortality rate, and there is no effective treatment. We aimed to investigate β-eudesmol molecular target of action in human CCA cell lines using the selected key molecules of apoptotic pathways. \r\n\r\n Materials and methods: Two CCA cell lines (HuH28 and HuCCT1) were assessed at different time points after β-eudesmol treatment for mRNA and protein expression profiles of caspase-3, -8, -9, p53, p21, Bcl-2, and Bax by real-time polymerase chain reaction and western blot, respectively. \r\n\r\n Results: β-eudesmol induced expressions of p21 and p53 in mRNA/protein level in HuH28 and HuCCT1 cells. These CCA cells also expressed caspase-3, -8, -9 and bax (mRNA and/or protein level) among others after β-eudesmol treatment indicating its role in both intrinsic and extrinsic caspase-dependent apoptotic pathways. \r\n\r\n Conclusion: The study demonstrated that β-eudesmol induced the expression of apoptosis pathway proteins, suggesting its potential role in promoting the caspase-dependent apoptotic pathway, and induction of the cell cycle arrest in CCA cell lines. β-eudesmol can be considered as a potential compound for further investigation as an anti-CCA agent. STN","prediction_labels":"ANIMAL"},{"cleaned":"feasibility safety long term photodynamic therapy pdt palliative treatment patients hilar cholangiocarcinoma background aim pdt important palliative option patients unresectable extrahepatic cholangiocarcinoma cc however results published date reported studies 6 mostly 4 pdt procedures furthermore clinical experience pdt combination chemotherapy limited purpose retrospective analysis evaluate feasibility safety multiple 4 14 settings pdt combined biliary drainage cases chemotherapy methods ten patients unresectable extrahepatic cc treated biliary stenting least 4 pdt procedures department 10 2005 08 2010 results ten patients male female 5 5 mean age 68 8 years range 54 81 years received least 4 pdt procedures analyzed patients underwent endoscopic biliary drainage nine patients received metallic stents one patient plastic stent 4 patients 40 bilateral metal stenting jostent selfx performed mean number pdt sessions 7 9 3 9 range 4 14 eight patients elevated bilirubin levels mean bilirubin admission 9 9 11 3 mg dl decreased average minimum 1 2 0 9 mg dl 3 months severe toxicity noted two patients received concomitant chemotherapy gemcis 1st line gemox plus cetuximab 2nd line median overall survival reached whereas estimated survival patients 47 6 months 95 ci 25 9 48 1 conclusion long term pdt patients extrahepatic cc feasible effective accompanied least cohort survival time 2 years pubmed","probabilities":0.9799733,"Title":"Feasibility and safety of long-term photodynamic therapy (PDT) in the palliative treatment of patients with hilar cholangiocarcinoma","Abstract":"BACKGROUND AND AIM: PDT is an important palliative option for patients with unresectable extrahepatic cholangiocarcinoma (CC). However, the results published to date reported on studies with no more than 6 (mostly up to 4) PDT procedures. Furthermore, the clinical experience of PDT in combination with chemotherapy is limited. The purpose of this retrospective analysis was to evaluate the feasibility and safety of multiple (4 to 14) settings of PDT, combined with biliary drainage, and (in some cases) with chemotherapy. - METHODS: Ten patients with unresectable extrahepatic CC were treated with biliary stenting and at least 4 PDT procedures in our department between 10/2005 and 08/2010. - RESULTS: Ten patients (male/female = 5/5), mean age 68.8 years (range, 54 - 81 years) who received at least 4 PDT procedures were analyzed. All patients underwent endoscopic biliary drainage. Nine patients received metallic stents and one patient a plastic stent. In 4 patients (40%) bilateral metal stenting (JoStent SelfX®) was performed. The mean number of PDT sessions was 7.9 ± 3.9 (range: 4 - 14). Eight patients had elevated bilirubin levels with a mean bilirubin at admission of 9.9 ± 11.3 mg/dL, which had decreased to an average minimum of 1.2 ± 0.9 mg/dL after 3 months. No severe toxicity was noted. Two patients received concomitant chemotherapy (GEMCIS as 1st line, GEMOX plus cetuximab as 2nd line). The median overall survival has not been reached, whereas the estimated survival of all patients was 47.6 months, 95% CI 25.9 - 48.1. - CONCLUSION: Long-term PDT in patients with extrahepatic CC is feasible and effective and is accompanied - at least in this cohort- by a survival time of more than 2 years.","Source":"PubMed","category":"HUMAN","training_data":"Feasibility and safety of long-term photodynamic therapy (PDT) in the palliative treatment of patients with hilar cholangiocarcinoma BACKGROUND AND AIM: PDT is an important palliative option for patients with unresectable extrahepatic cholangiocarcinoma (CC). However, the results published to date reported on studies with no more than 6 (mostly up to 4) PDT procedures. Furthermore, the clinical experience of PDT in combination with chemotherapy is limited. The purpose of this retrospective analysis was to evaluate the feasibility and safety of multiple (4 to 14) settings of PDT, combined with biliary drainage, and (in some cases) with chemotherapy. - METHODS: Ten patients with unresectable extrahepatic CC were treated with biliary stenting and at least 4 PDT procedures in our department between 10/2005 and 08/2010. - RESULTS: Ten patients (male/female = 5/5), mean age 68.8 years (range, 54 - 81 years) who received at least 4 PDT procedures were analyzed. All patients underwent endoscopic biliary drainage. Nine patients received metallic stents and one patient a plastic stent. In 4 patients (40%) bilateral metal stenting (JoStent SelfX®) was performed. The mean number of PDT sessions was 7.9 ± 3.9 (range: 4 - 14). Eight patients had elevated bilirubin levels with a mean bilirubin at admission of 9.9 ± 11.3 mg/dL, which had decreased to an average minimum of 1.2 ± 0.9 mg/dL after 3 months. No severe toxicity was noted. Two patients received concomitant chemotherapy (GEMCIS as 1st line, GEMOX plus cetuximab as 2nd line). The median overall survival has not been reached, whereas the estimated survival of all patients was 47.6 months, 95% CI 25.9 - 48.1. - CONCLUSION: Long-term PDT in patients with extrahepatic CC is feasible and effective and is accompanied - at least in this cohort- by a survival time of more than 2 years. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors pancreatoduodenectomy distal bile duct cancer prognostic factors influencing long term survival radical resection distal bile duct cancer well established rarity malignancy goal study identify main prognostic factors patients undergoing pancreatoduodenectomy distal bile duct carcinoma retrospective study consisting 122 patients distal bile duct cancer underwent pancreatoduodenectomy three major university hospitals performed identify main prognostic factors major surgical complications occurred 40 patients 32 8 eight died 6 6 hospital overall actuarial survival excluding hospital deaths 1 3 5 year follow 82 9 49 4 32 7 per cent respectively median survival 36 months univariate analysis showed papillary tumor p 0 045 negative surgical margin r0 resection p 0 005 earlier pt p 0 005 ptnm stage p 0 001 absence lymph node involvement p 0 0001 significant predictors survival multivariate analysis lymph node metastasis shown independent prognostic factor survival p 0 036 lymph node involvement important survival predictor whipple resection patients distal cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic factors after pancreatoduodenectomy for distal bile duct cancer","Abstract":"Prognostic factors influencing long-term survival after radical resection for distal bile duct cancer have not been well established because of the rarity of this malignancy. The goal of this study was to identify main prognostic factors in patients undergoing pancreatoduodenectomy for distal bile duct carcinoma. A retrospective study consisting of 122 patients with distal bile duct cancer who underwent pancreatoduodenectomy in three major university hospitals was performed to identify the main prognostic factors. Major surgical complications occurred in 40 patients (32.8%), of whom eight died (6.6%) in the hospital. Overall actuarial survival (excluding hospital deaths) at 1-, 3-, and 5-year follow-up was 82.9, 49.4, and 32.7 per cent, respectively, with a median survival of 36 months. Univariate analysis showed that papillary tumor (P = 0.045), negative surgical margin (R0 resection, P = 0.005), earlier pT (P = 0.005), pTNM stage (P < 0.001), and absence of lymph node involvement (P < 0.0001) were significant predictors of survival. On multivariate analysis, only lymph node metastasis was shown to be an independent prognostic factor of survival (P = 0.036). Lymph node involvement was the most important survival predictor after a Whipple resection in patients with distal cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors after pancreatoduodenectomy for distal bile duct cancer Prognostic factors influencing long-term survival after radical resection for distal bile duct cancer have not been well established because of the rarity of this malignancy. The goal of this study was to identify main prognostic factors in patients undergoing pancreatoduodenectomy for distal bile duct carcinoma. A retrospective study consisting of 122 patients with distal bile duct cancer who underwent pancreatoduodenectomy in three major university hospitals was performed to identify the main prognostic factors. Major surgical complications occurred in 40 patients (32.8%), of whom eight died (6.6%) in the hospital. Overall actuarial survival (excluding hospital deaths) at 1-, 3-, and 5-year follow-up was 82.9, 49.4, and 32.7 per cent, respectively, with a median survival of 36 months. Univariate analysis showed that papillary tumor (P = 0.045), negative surgical margin (R0 resection, P = 0.005), earlier pT (P = 0.005), pTNM stage (P < 0.001), and absence of lymph node involvement (P < 0.0001) were significant predictors of survival. On multivariate analysis, only lymph node metastasis was shown to be an independent prognostic factor of survival (P = 0.036). Lymph node involvement was the most important survival predictor after a Whipple resection in patients with distal cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"health related quality life prognostic factor patients advanced cancer background evidence continues accumulate regarding association health related quality life hrqol survival across chronic diseases objectives current study investigate prognostic value hrqol patients hepatocellular carcinoma cholangiocarcinoma adjusting sociodemographics disease related factors treatment related factors methods total 321 patients diagnosed hepatocellular cholangiocarcinoma administered functional assessment cancer therapy hepatobiliary instrument cox regression kaplan meier survival analyses performed test association 5 domains hrqol survival results using cox regression overall hrqol found significantly associated survival p 003 adjusting demographics disease specific factors treatment subscales functional assessment cancer therapy hepatobiliary including physical well p 02 symptoms side effects subscales p 05 also found significantly associated survival adjusting demographics disease specific factors treatment conclusions hrqol found prognostic survival patients hepatocellular cholangiocarcinoma covarying demographics disease specific factors treatment stratifying patients based hrqol testing novel treatments may recommended health related quality life found prognostic survival patients hepatocellular cholangiocarcinoma controlling demographics disease specific factors treatment related factors pubmed","probabilities":0.9799733,"Title":"Health-related quality of life as a prognostic factor in patients with advanced cancer","Abstract":"BACKGROUND: Evidence continues to accumulate regarding the association between health-related quality of life (HRQoL) and survival across chronic diseases. The objectives of the current study were to investigate the prognostic value of HRQoL in patients with hepatocellular carcinoma and cholangiocarcinoma after adjusting for sociodemographics, disease-related factors, and treatment-related factors. METHODS: A total of 321 patients diagnosed with hepatocellular or cholangiocarcinoma were administered the Functional Assessment of Cancer Therapy-Hepatobiliary instrument. Cox regression and Kaplan-Meier survival analyses were performed to test the association between the 5 domains of HRQoL and survival. RESULTS: Using Cox regression, overall HRQoL was found to be significantly associated with survival (P = .003) after adjusting for demographics, disease-specific factors, and treatment. Subscales of the Functional Assessment of Cancer Therapy-Hepatobiliary, including the Physical Well-Being (P = .02) and the Symptoms and Side Effects subscales (P = .05), were also found to be significantly associated with survival after adjusting for demographics, disease-specific factors, and treatment. CONCLUSIONS: HRQoL was found to be prognostic of survival in patients with hepatocellular and cholangiocarcinoma while covarying for demographics, disease-specific factors, and treatment. Stratifying patients based on HRQoL when testing novel treatments may be recommended. Health-related quality of life was found to be prognostic of survival in patients with hepatocellular and cholangiocarcinoma while controlling for demographics, disease-specific factors, and treatment-related factors.","Source":"PubMed","category":"HUMAN","training_data":"Health-related quality of life as a prognostic factor in patients with advanced cancer BACKGROUND: Evidence continues to accumulate regarding the association between health-related quality of life (HRQoL) and survival across chronic diseases. The objectives of the current study were to investigate the prognostic value of HRQoL in patients with hepatocellular carcinoma and cholangiocarcinoma after adjusting for sociodemographics, disease-related factors, and treatment-related factors. METHODS: A total of 321 patients diagnosed with hepatocellular or cholangiocarcinoma were administered the Functional Assessment of Cancer Therapy-Hepatobiliary instrument. Cox regression and Kaplan-Meier survival analyses were performed to test the association between the 5 domains of HRQoL and survival. RESULTS: Using Cox regression, overall HRQoL was found to be significantly associated with survival (P = .003) after adjusting for demographics, disease-specific factors, and treatment. Subscales of the Functional Assessment of Cancer Therapy-Hepatobiliary, including the Physical Well-Being (P = .02) and the Symptoms and Side Effects subscales (P = .05), were also found to be significantly associated with survival after adjusting for demographics, disease-specific factors, and treatment. CONCLUSIONS: HRQoL was found to be prognostic of survival in patients with hepatocellular and cholangiocarcinoma while covarying for demographics, disease-specific factors, and treatment. Stratifying patients based on HRQoL when testing novel treatments may be recommended. Health-related quality of life was found to be prognostic of survival in patients with hepatocellular and cholangiocarcinoma while controlling for demographics, disease-specific factors, and treatment-related factors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"relevant prognostic factors influencing outcome patients surgical resection distal cholangiocarcinoma background distal cholangiocarcinoma dcc rare last decade increasing malignancy associated poor prognosis according present knowledge curative surgery chance long term survival study performed evaluate prognostic factors outcome patients undergoing curative surgery distal cholangiocarcinoma methods 75 patients underwent surgery january 2000 december 2014 dcc curative intention analysed retrospectively potential prognostic factors survival investigated including extent surgery using purposeful selection covariates multivariable cox regression modeling results preoperative biliary stenting hazard ratio hr 2 530 95 ci 1 146 6 464 p 0 020 extent surgery case positive histological venous invasion hr 1 209 95 ci 1 017 1 410 p 0 032 lymph node staging hr 2 183 95 ci 1 250 3 841 p 0 006 perineural invasion hr 2 118 95 ci 1 147 4 054 p 0 016 postoperative complications graded points according clavien dindo hr 1 395 95 ci 1 148 1 699 p 0 001 indentified independent significant risk factors survival patients receiving preoperative biliary stenting showed prolonged duration onset symptoms date operation p 0 048 conclusions preoperative biliary stenting reduces survival possibly due delayed surgery extent surgery independent risk factor survival except patients concomitant histological venous invasion oncological factors postoperative surgical complications independent prognostic factors survival pubmed","probabilities":0.9799733,"Title":"Relevant prognostic factors influencing outcome of patients after surgical resection of distal cholangiocarcinoma","Abstract":"BACKGROUND: Distal cholangiocarcinoma (DCC) is a rare but over the last decade increasing malignancy and is associated with poor prognosis. According to the present knowledge curative surgery is the only chance for long term survival. This study was performed to evaluate prognostic factors for the outcome of patients undergoing curative surgery for distal cholangiocarcinoma. METHODS: 75 patients who underwent surgery between January 2000 and December 2014 for DCC in curative intention were analysed retrospectively. Potential prognostic factors for survival were investigated including the extent of surgery using purposeful selection of covariates in multivariable Cox regression modeling. RESULTS: Preoperative biliary stenting (Hazard ratio (HR): 2.530; 95%-CI: 1.146-6.464, p = 0.020), the extent of surgery in case of positive histological venous invasion (HR: 1.209; 95%-CI: 1.017-1.410, p = 0.032), lymph node staging (HR: 2.183; 95%-CI: 1.250-3.841, p = 0.006), perineural invasion (HR: 2.118; 95%-CI: 1.147-4.054, p = 0.016) and postoperative complications graded in points according to Clavien-Dindo (HR: 1.395; 95%-CI: 1.148-1.699, p = 0.001) were indentified as independent significant risk factors for survival. Patients receiving preoperative biliary stenting showed prolonged duration between onset of symptoms and date of operation (p = 0.048). CONCLUSIONS: Preoperative biliary stenting reduces survival possibly due to delayed surgery. The extent of surgery is not an independent risk factor for survival except for patients with concomitant histological venous invasion. Oncological factors and postoperative surgical complications are independent prognostic factors for survival.","Source":"PubMed","category":"HUMAN","training_data":"Relevant prognostic factors influencing outcome of patients after surgical resection of distal cholangiocarcinoma BACKGROUND: Distal cholangiocarcinoma (DCC) is a rare but over the last decade increasing malignancy and is associated with poor prognosis. According to the present knowledge curative surgery is the only chance for long term survival. This study was performed to evaluate prognostic factors for the outcome of patients undergoing curative surgery for distal cholangiocarcinoma. METHODS: 75 patients who underwent surgery between January 2000 and December 2014 for DCC in curative intention were analysed retrospectively. Potential prognostic factors for survival were investigated including the extent of surgery using purposeful selection of covariates in multivariable Cox regression modeling. RESULTS: Preoperative biliary stenting (Hazard ratio (HR): 2.530; 95%-CI: 1.146-6.464, p = 0.020), the extent of surgery in case of positive histological venous invasion (HR: 1.209; 95%-CI: 1.017-1.410, p = 0.032), lymph node staging (HR: 2.183; 95%-CI: 1.250-3.841, p = 0.006), perineural invasion (HR: 2.118; 95%-CI: 1.147-4.054, p = 0.016) and postoperative complications graded in points according to Clavien-Dindo (HR: 1.395; 95%-CI: 1.148-1.699, p = 0.001) were indentified as independent significant risk factors for survival. Patients receiving preoperative biliary stenting showed prolonged duration between onset of symptoms and date of operation (p = 0.048). CONCLUSIONS: Preoperative biliary stenting reduces survival possibly due to delayed surgery. The extent of surgery is not an independent risk factor for survival except for patients with concomitant histological venous invasion. Oncological factors and postoperative surgical complications are independent prognostic factors for survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumoral line 1 hypomethylation associated poor survival patients intrahepatic cholangiocarcinoma background dna methylation changes occurring cancer cells featured promoter cpg island hypermethylation diffuse genomic hypomethylation long interspersed element 1 line 1 repeated interspersed manner estimated 500 000 copies per genome line 1 cpg sites 5 untranslated region methylated heavily normal cells undergoes demethylation association cancerization however little information available regarding line 1 hypomethylation prognostic implication intrahepatic cholangiocarcinomas methods total 172 cases intrahepatic cholangiocarcinomas analyzed methylation levels four cpg sites line 1 using bisulfite pyrosequencing examined relation tumoral line 1 methylation level clinicopathological features including survival results tumor differentiation lymphatic invasion stage associated low average methylation level line 1 four cpg sites line 1 methylation level tended lower high grade differentiation lymphatic emboli higher stage line 1 hypomethylation significantly linked lower cancer specific survival patients intrahepatic cholangiocarcinoma found independent prognostic parameter conclusions findings suggest tumoral line 1 hypomethylation molecular biomarker heralding poor prognosis patients intrahepatic cholangiocarcinoma findings need validated study pubmed","probabilities":0.9799733,"Title":"Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: DNA methylation changes occurring in cancer cells are featured with both promoter CpG island hypermethylation and diffuse genomic hypomethylation. Long interspersed element-1 (LINE-1) is repeated in an interspersed manner with an estimated 500,000 copies per genome. LINE-1 has its CpG sites of the 5' untranslated region methylated heavily in normal cells and undergoes demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas. METHODS: A total of 172 cases of intrahepatic cholangiocarcinomas were analyzed for their methylation levels at four CpG sites of LINE-1 using bisulfite pyrosequencing. We examined the relation between tumoral LINE-1 methylation level and clinicopathological features, including survival. RESULTS: Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites; LINE-1 methylation level tended to be lower in high-grade differentiation, lymphatic emboli, and higher T stage. LINE-1 hypomethylation was significantly linked with lower cancer-specific survival in patients with intrahepatic cholangiocarcinoma and was found to be an independent prognostic parameter. CONCLUSIONS: Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. Our findings need to be validated in further study.","Source":"PubMed","category":"HUMAN","training_data":"Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma BACKGROUND: DNA methylation changes occurring in cancer cells are featured with both promoter CpG island hypermethylation and diffuse genomic hypomethylation. Long interspersed element-1 (LINE-1) is repeated in an interspersed manner with an estimated 500,000 copies per genome. LINE-1 has its CpG sites of the 5' untranslated region methylated heavily in normal cells and undergoes demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas. METHODS: A total of 172 cases of intrahepatic cholangiocarcinomas were analyzed for their methylation levels at four CpG sites of LINE-1 using bisulfite pyrosequencing. We examined the relation between tumoral LINE-1 methylation level and clinicopathological features, including survival. RESULTS: Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites; LINE-1 methylation level tended to be lower in high-grade differentiation, lymphatic emboli, and higher T stage. LINE-1 hypomethylation was significantly linked with lower cancer-specific survival in patients with intrahepatic cholangiocarcinoma and was found to be an independent prognostic parameter. CONCLUSIONS: Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. Our findings need to be validated in further study. PubMed","prediction_labels":"HUMAN"},{"cleaned":"management hilum infiltrating tumors liver impact experience standardization outcome background primary endpoint study evaluate outcome surgery perihilar cholangiocarcinoma high volume tertiary referral center methods study population consisted 196 consecutive patients histologically confirmed perihilar cholangiocarcinoma phc candidates surgical treatment factors affecting postoperative morbidity evaluated whole series primary endpoint stratification patients according following criteria perioperative management protocol implementation b monocentric management secondary endpoint results postoperative morbidity rate 51 5 mortality 4 1 frequent cause death postoperative liver failure multivariate analysis factors affecting risk morbidity side hepatectomy liver volume intraoperative blood loss preoperative optimization single center management patients treated according preoperative optimization protocol well patients monocentric management experienced significant reduction postoperative morbidity preoperative optimization single center management significantly affected even long term outcome patients conclusion despite continuous improvement surgical field hilum infiltrating tumors still remain associated therapeutic management challenges correct preoperative management tertiary referral center provides benefit terms morbidity mortality thus improving long term results pubmed","probabilities":0.9799733,"Title":"Management of hilum infiltrating tumors of the liver: The impact of experience and standardization on outcome","Abstract":"BACKGROUND: The primary endpoint of this study was to evaluate the outcome of surgery for perihilar cholangiocarcinoma in a high-volume tertiary referral center. METHODS: The study population consisted of 196 consecutive patients with histologically confirmed perihilar cholangiocarcinoma-PHC-who were candidates to surgical treatment. Factors affecting postoperative morbidity were evaluated in the whole series (primary endpoint) and after stratification of patients according to the following criteria: (a) perioperative management protocol implementation; (b) monocentric management (secondary endpoint). RESULTS: The postoperative morbidity rate was 51.5% and mortality 4.1%. The most frequent cause of death was postoperative liver failure. At multivariate analysis, factors affecting the risk of morbidity were: side of hepatectomy, liver volume, intraoperative blood loss, preoperative optimization and single-center management. Patients treated according to preoperative optimization protocol, as well as patients with monocentric management experienced a significant reduction of postoperative morbidity. Preoperative optimization and single-center management significantly affected even long term outcome of patients. CONCLUSION: Despite continuous improvement in the surgical field, hilum-infiltrating tumors still remain associated with therapeutic and management challenges: a correct preoperative management in a tertiary referral center provides a benefit in terms of morbidity and mortality, thus improving long term results.","Source":"PubMed","category":"HUMAN","training_data":"Management of hilum infiltrating tumors of the liver: The impact of experience and standardization on outcome BACKGROUND: The primary endpoint of this study was to evaluate the outcome of surgery for perihilar cholangiocarcinoma in a high-volume tertiary referral center. METHODS: The study population consisted of 196 consecutive patients with histologically confirmed perihilar cholangiocarcinoma-PHC-who were candidates to surgical treatment. Factors affecting postoperative morbidity were evaluated in the whole series (primary endpoint) and after stratification of patients according to the following criteria: (a) perioperative management protocol implementation; (b) monocentric management (secondary endpoint). RESULTS: The postoperative morbidity rate was 51.5% and mortality 4.1%. The most frequent cause of death was postoperative liver failure. At multivariate analysis, factors affecting the risk of morbidity were: side of hepatectomy, liver volume, intraoperative blood loss, preoperative optimization and single-center management. Patients treated according to preoperative optimization protocol, as well as patients with monocentric management experienced a significant reduction of postoperative morbidity. Preoperative optimization and single-center management significantly affected even long term outcome of patients. CONCLUSION: Despite continuous improvement in the surgical field, hilum-infiltrating tumors still remain associated with therapeutic and management challenges: a correct preoperative management in a tertiary referral center provides a benefit in terms of morbidity and mortality, thus improving long term results. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long non coding rna hotair promotes tumorigenesis forecasts poor prognosis cholangiocarcinoma cholangiocarcinoma cca arising neoplastic transformation cholangiocytes increasing incidence worldwide unfortunately large amount cca patients lost chance surgery hard diagnose early stages long non coding rnas lncrnas closely associated development progression various malignant tumors hox transcript antisense intergenic hotair negative prognostic factor patients gastric liver pancreatic carcinoma transcription levels functional roles cca still unknown therefore aimed explore effect hotair cca including cell proliferation apoptosis migration invasion epithelial mesenchymal transition emt results showed hotair highly expressed cca tissue samples cell lines compared corresponding normal bile duct tissues human intrahepatic biliary epithelial cells hibec overexpression closely correlated tumor size tnm stage postoperative recurrence cca patients moreover regulation hotair correlation prognosis cca patients knockdown hotair sirnas significantly decreased migration invasion increased apoptosis cca cells vitro overall study revealed hotair may play new potential therapeutic target forecast poor prognosis fatal disease stn","probabilities":0.9467213,"Title":"Long Non-Coding Rna Hotair Promotes Tumorigenesis And Forecasts A Poor Prognosis In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) arising from the neoplastic transformation of cholangiocytes with increasing incidence in the worldwide. Unfortunately, a large amount of CCA patients lost their chance for surgery because it is hard to diagnose in the early stages. Long non-coding RNAs (lncRNAs) is closely associated with development and progression of various malignant tumors. Hox transcript antisense intergenic (HOTAIR), a negative prognostic factor for patients with gastric, liver and pancreatic carcinoma. Its transcription levels and functional roles in CCA is still unknown. Therefore, we aimed to explore the effect of HOTAIR in CCA including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). The results showed that HOTAIR was highly expressed both in CCA tissue samples and cell lines compared with corresponding normal bile duct tissues and Human intrahepatic biliary epithelial cells (HIBEC). Its overexpression was closely correlated with Tumor size, TNM stage and postoperative recurrence in CCA patients. Moreover, up-regulation of HOTAIR has correlation with prognosis in CCA patients. Knockdown of HOTAIR by siRNAs significantly decreased the migration and invasion but increased apoptosis of CCA cells in vitro. Overall, our study revealed that HOTAIR may play as a new potential therapeutic target and forecast poor prognosis for this fatal disease.","Source":"STN","category":"ANIMAL","training_data":"Long Non-Coding Rna Hotair Promotes Tumorigenesis And Forecasts A Poor Prognosis In Cholangiocarcinoma Cholangiocarcinoma (CCA) arising from the neoplastic transformation of cholangiocytes with increasing incidence in the worldwide. Unfortunately, a large amount of CCA patients lost their chance for surgery because it is hard to diagnose in the early stages. Long non-coding RNAs (lncRNAs) is closely associated with development and progression of various malignant tumors. Hox transcript antisense intergenic (HOTAIR), a negative prognostic factor for patients with gastric, liver and pancreatic carcinoma. Its transcription levels and functional roles in CCA is still unknown. Therefore, we aimed to explore the effect of HOTAIR in CCA including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). The results showed that HOTAIR was highly expressed both in CCA tissue samples and cell lines compared with corresponding normal bile duct tissues and Human intrahepatic biliary epithelial cells (HIBEC). Its overexpression was closely correlated with Tumor size, TNM stage and postoperative recurrence in CCA patients. Moreover, up-regulation of HOTAIR has correlation with prognosis in CCA patients. Knockdown of HOTAIR by siRNAs significantly decreased the migration and invasion but increased apoptosis of CCA cells in vitro. Overall, our study revealed that HOTAIR may play as a new potential therapeutic target and forecast poor prognosis for this fatal disease. STN","prediction_labels":"ANIMAL"},{"cleaned":"common variant precursor mir 146a sequence predispose cholangiocarcinoma large european cohort background micro rnas mirnas small non coding rna species considered fine tune basic cellular functions modulating target gene translation mrna stability common g c polymorphism rs2910164 precursor pre mir 146a gene engaged nf b signaling apoptosis pathways reported modulate genetic risk hepatocellular carcinoma increased g allelic production mature mir 146a investigated rs2910164 large european based cholangiocarcinoma cca cohort methods recruited 182 cca patients 350 controls three academic medical centers genotyping rs2910164 performed pcr based assays 5 nuclease fluorescence detection genotype frequencies tested consistency hardy weinberg equilibrium using exact test allelic genotypic differences patients controls assessed chi square test armitage trend test exploratory subgroup analyses included gender tumor localization extra versus intrahepatic cca early onset cca results genotype distributions consistent hardy weinberg equilibrium significant differences either allele genotype distributions detected cca control groups respective subgroups investigated however trend protective effect heterozygous single nucleotide polymorphism state gc indicated underrepresentation cca group general 29 vs 35 p 0 18 particular extrahepatic tumor sites 26 vs 35 0 67 95 ci 0 43 1 02 p 0 065 conclusions data support prominent contribution pre mir 146a sequence variant genetic predisposition cca however current studies functionally characterizing rs2910164 proposed distinct repertoires target genes addressed genotype specific mature mir 146a species given detected trend towards potentially protective role gc heterozygosity subtle modulation genetic cca risk pre mir 146a gc genotype may exist evaluated pubmed","probabilities":0.5555556,"Title":"A common variant in the precursor miR-146a sequence does not predispose to cholangiocarcinoma in a large European cohort","Abstract":"BACKGROUND: Micro-RNAs (miRNAs) are small, non-coding RNA species considered to fine-tune basic cellular functions by modulating target gene translation and/or mRNA stability. A common G/C polymorphism (rs2910164) in the precursor (pre-) miR-146a gene engaged in NF-κB signaling and apoptosis pathways has been reported to modulate the genetic risk of hepatocellular carcinoma by increased G-allelic production of mature miR-146a. We investigated rs2910164 in a large European-based cholangiocarcinoma (CCA) cohort. METHODS: We recruited 182 CCA patients and 350 controls in three academic medical centers. Genotyping for rs2910164 was performed by PCR-based assays with 5'-nuclease and fluorescence detection. Genotype frequencies were tested for consistency with the Hardy-Weinberg equilibrium using an exact test; allelic and genotypic differences between the patients and controls were assessed by the Chi-square test and Armitage's trend test. Exploratory subgroup analyses included gender, tumor localization (extra- versus intrahepatic CCA) and early-onset CCA. RESULTS: Genotype distributions were consistent with the Hardy-Weinberg equilibrium. No significant differences in either allele or genotype distributions were detected between the CCA and control groups or the respective subgroups investigated. However, there was a trend for a protective effect of the heterozygous single-nucleotide polymorphism state GC, as indicated by an underrepresentation in the CCA group in general (29% vs 35%; P=0.18) and, in particular, for extrahepatic tumor sites (26% vs 35%; OR=0.67; 95% CI, 0.43-1.02; P=0.065). CONCLUSIONS: Our data do not support a prominent contribution of the pre-miR-146a sequence variant in the genetic predisposition to CCA. However, current studies functionally characterizing rs2910164 have proposed that distinct repertoires of target genes are addressed by genotype-specific mature miR-146a species. Given the detected trend towards a potentially protective role of GC heterozygosity, a subtle modulation of genetic CCA risk by the pre-miR-146a GC genotype may exist and should be evaluated further.","Source":"PubMed","category":"HUMAN","training_data":"A common variant in the precursor miR-146a sequence does not predispose to cholangiocarcinoma in a large European cohort BACKGROUND: Micro-RNAs (miRNAs) are small, non-coding RNA species considered to fine-tune basic cellular functions by modulating target gene translation and/or mRNA stability. A common G/C polymorphism (rs2910164) in the precursor (pre-) miR-146a gene engaged in NF-κB signaling and apoptosis pathways has been reported to modulate the genetic risk of hepatocellular carcinoma by increased G-allelic production of mature miR-146a. We investigated rs2910164 in a large European-based cholangiocarcinoma (CCA) cohort. METHODS: We recruited 182 CCA patients and 350 controls in three academic medical centers. Genotyping for rs2910164 was performed by PCR-based assays with 5'-nuclease and fluorescence detection. Genotype frequencies were tested for consistency with the Hardy-Weinberg equilibrium using an exact test; allelic and genotypic differences between the patients and controls were assessed by the Chi-square test and Armitage's trend test. Exploratory subgroup analyses included gender, tumor localization (extra- versus intrahepatic CCA) and early-onset CCA. RESULTS: Genotype distributions were consistent with the Hardy-Weinberg equilibrium. No significant differences in either allele or genotype distributions were detected between the CCA and control groups or the respective subgroups investigated. However, there was a trend for a protective effect of the heterozygous single-nucleotide polymorphism state GC, as indicated by an underrepresentation in the CCA group in general (29% vs 35%; P=0.18) and, in particular, for extrahepatic tumor sites (26% vs 35%; OR=0.67; 95% CI, 0.43-1.02; P=0.065). CONCLUSIONS: Our data do not support a prominent contribution of the pre-miR-146a sequence variant in the genetic predisposition to CCA. However, current studies functionally characterizing rs2910164 have proposed that distinct repertoires of target genes are addressed by genotype-specific mature miR-146a species. Given the detected trend towards a potentially protective role of GC heterozygosity, a subtle modulation of genetic CCA risk by the pre-miR-146a GC genotype may exist and should be evaluated further. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"surgical strategies unexpected gallbladder carcinoma objective explore surgical strategies unexpected gallbladder carcinoma ugc patients methods study hospital records performed 26 patients ugc treated institution january 1990 december 2002 surgical therapies disease prognosis analyzed results five cases gbc noted open cholecystectomy oc 15 confirmed minicholecystectomy mc 6 identified laparoscopic lc surgery patients nevin stage gallbladder carcinoma gbc survived 3 years patients stage iii gbc died within 2 years patients stage iv gbc died within 1 year conclusions caution must taken high risk conditions atypical ultrasonography gallbladder encountered examination frozen sections performed routinely cases reduce rates misdiagnosis surgery effective treatment gbc stn","probabilities":0.9799733,"Title":"Surgical Strategies For Unexpected Gallbladder Carcinoma","Abstract":"Objective: To explore surgical strategies for unexpected gallbladder carcinoma (UGC). \r\n\r\n Patients and methods: A study of hospital records was performed in 26 patients with UGC treated in our institution from January 1990 to December 2002. The surgical therapies and disease prognosis were analyzed. \r\n\r\n Results: Five cases of GBC were noted during open cholecystectomy (OC) and 15 were confirmed during minicholecystectomy (MC), while were 6 identified during laparoscopic (LC) surgery; all patients with Nevin Stage I gallbladder carcinoma (GBC) survived > 3 years; patients with Stage III GBC died within 2 years and patients with Stage IV GBC died within 1 year. \r\n\r\n Conclusions: Caution must be taken when high risk conditions and atypical ultrasonography of gallbladder are encountered. Examination of frozen sections should be performed routinely in all cases to reduce the rates of misdiagnosis. Surgery is an effective treatment for GBC.","Source":"STN","category":"HUMAN","training_data":"Surgical Strategies For Unexpected Gallbladder Carcinoma Objective: To explore surgical strategies for unexpected gallbladder carcinoma (UGC). \r\n\r\n Patients and methods: A study of hospital records was performed in 26 patients with UGC treated in our institution from January 1990 to December 2002. The surgical therapies and disease prognosis were analyzed. \r\n\r\n Results: Five cases of GBC were noted during open cholecystectomy (OC) and 15 were confirmed during minicholecystectomy (MC), while were 6 identified during laparoscopic (LC) surgery; all patients with Nevin Stage I gallbladder carcinoma (GBC) survived > 3 years; patients with Stage III GBC died within 2 years and patients with Stage IV GBC died within 1 year. \r\n\r\n Conclusions: Caution must be taken when high risk conditions and atypical ultrasonography of gallbladder are encountered. Examination of frozen sections should be performed routinely in all cases to reduce the rates of misdiagnosis. Surgery is an effective treatment for GBC. STN","prediction_labels":"HUMAN"},{"cleaned":"cancer incidence patterns oldest ages using expanded age categories seer registry data 2010 census population older age groups continue account increasing portion us population burden cancer age associated disease becomes larger public health concern due limited population data however disease surveillance statistics typically truncated age 84 years grouped terminal age category 85 years used detailed older age data 2010 census conjunction surveillance epidemiology end results cancer registry records 2008 2012 diagnoses estimate 5 year age specific incidence rates ages 90 94 years 95 years major cancers overall cancer rates increased maximum 80 89 year ranges subsequently declined incidence rates peaked younger age groups several specific cancers including breast cervix uteri corpus uteri prostate whereas rates colon rectum leukemia melanoma pancreas stomach urinary bladder continued rise among men women early 90s rates liver intrahepatic bile duct cancer showed initial spike among men aged 60 64 years followed larger peak ages 80 84 since age specific incidence patterns based cross sectional data may vary time cancers eg lung liver prevalence major risk factors change across birth cohorts future studies using new publicly available databases additional older age groups examine cancer subtypes defined emerging understanding molecular biomarkers need accurate annual post census population estimates older age categories enable continuous monitoring disease dynamics among rapidly growing population groups pubmed","probabilities":0.9799733,"Title":"Cancer Incidence Patterns in the Oldest Ages Using Expanded Age Categories from SEER Registry Data and the 2010 Census Population","Abstract":"As older age groups continue to account for an increasing portion of the US population, the burden of cancer and other age-associated disease becomes a larger public health concern. Due to limited population data, however, disease surveillance statistics are typically truncated at age 84 years and then grouped into a terminal age category of ≥85 years. We used more detailed older age data from the 2010 census in conjunction with Surveillance, Epidemiology, and End Results cancer registry records for 2008-2012 diagnoses to estimate 5-year age-specific incidence rates through ages 90-94 years and ≥95 years for major cancers. Overall cancer rates increased to a maximum in the 80-89-year ranges and subsequently declined. Incidence rates peaked in younger age groups for several specific cancers, including breast, cervix uteri, corpus uteri, and prostate. Whereas, rates for colon and rectum, leukemia, melanoma, pancreas, stomach, and urinary bladder continued to rise among men and women into their early 90s. Rates of liver and intrahepatic bile duct cancer showed an initial spike among men aged 60-64 years followed by a larger peak at ages 80-84. Since these age-specific incidence patterns were based on cross-sectional data, they may vary over time for some cancers (eg, lung and liver) as the prevalence of major risk factors change across birth cohorts. Future studies using new, publicly available databases with these additional older age groups can examine cancer subtypes defined by our emerging understanding of molecular biomarkers. There is a need for accurate annual post-census population estimates for older age categories to enable continuous monitoring of disease dynamics among these rapidly growing population groups.","Source":"PubMed","category":"HUMAN","training_data":"Cancer Incidence Patterns in the Oldest Ages Using Expanded Age Categories from SEER Registry Data and the 2010 Census Population As older age groups continue to account for an increasing portion of the US population, the burden of cancer and other age-associated disease becomes a larger public health concern. Due to limited population data, however, disease surveillance statistics are typically truncated at age 84 years and then grouped into a terminal age category of ≥85 years. We used more detailed older age data from the 2010 census in conjunction with Surveillance, Epidemiology, and End Results cancer registry records for 2008-2012 diagnoses to estimate 5-year age-specific incidence rates through ages 90-94 years and ≥95 years for major cancers. Overall cancer rates increased to a maximum in the 80-89-year ranges and subsequently declined. Incidence rates peaked in younger age groups for several specific cancers, including breast, cervix uteri, corpus uteri, and prostate. Whereas, rates for colon and rectum, leukemia, melanoma, pancreas, stomach, and urinary bladder continued to rise among men and women into their early 90s. Rates of liver and intrahepatic bile duct cancer showed an initial spike among men aged 60-64 years followed by a larger peak at ages 80-84. Since these age-specific incidence patterns were based on cross-sectional data, they may vary over time for some cancers (eg, lung and liver) as the prevalence of major risk factors change across birth cohorts. Future studies using new, publicly available databases with these additional older age groups can examine cancer subtypes defined by our emerging understanding of molecular biomarkers. There is a need for accurate annual post-census population estimates for older age categories to enable continuous monitoring of disease dynamics among these rapidly growing population groups. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression cytoskeleton associated protein 4 related lymphatic metastasis indicates prognosis intrahepatic cholangiocarcinoma patients surgery resection objective study investigate clinical significance ckap4 intrahepatic cholangiocellular carcinoma icc ckap4 expression determined cohort containing 173 cases icc patients found ckap4 overexpressed majority icc cases significantly associated tumor size distant metastasis lymph node metastasis uicc tnm stage features kaplan meier cox regression data indicated ckap4 correlated favorable clinical outcome independent predictor overall survival hr 0 646 95 ci 0 463 0 900 p 0 010 thus ckap4 may serve prognostic marker icc patients pubmed","probabilities":0.9799733,"Title":"Expression of cytoskeleton-associated protein 4 is related to lymphatic metastasis and indicates prognosis of intrahepatic cholangiocarcinoma patients after surgery resection","Abstract":"The objective of the study was to investigate the clinical significance of CKAP4 in intrahepatic cholangiocellular carcinoma (ICC). CKAP4 expression was determined in a cohort containing 173 cases of ICC patients. We found that CKAP4 was overexpressed in the majority of ICC cases and was significantly associated with tumor size, distant metastasis, lymph node metastasis, UICC and TNM stage features. Kaplan-Meier and Cox regression data indicated that CKAP4 was correlated with favorable clinical outcome and was an independent predictor for overall survival (HR, 0.646; 95% CI, 0.463-0.900 [p=0.010]). Thus, CKAP4 may serve as a prognostic marker of ICC patients.","Source":"PubMed","category":"HUMAN","training_data":"Expression of cytoskeleton-associated protein 4 is related to lymphatic metastasis and indicates prognosis of intrahepatic cholangiocarcinoma patients after surgery resection The objective of the study was to investigate the clinical significance of CKAP4 in intrahepatic cholangiocellular carcinoma (ICC). CKAP4 expression was determined in a cohort containing 173 cases of ICC patients. We found that CKAP4 was overexpressed in the majority of ICC cases and was significantly associated with tumor size, distant metastasis, lymph node metastasis, UICC and TNM stage features. Kaplan-Meier and Cox regression data indicated that CKAP4 was correlated with favorable clinical outcome and was an independent predictor for overall survival (HR, 0.646; 95% CI, 0.463-0.900 [p=0.010]). Thus, CKAP4 may serve as a prognostic marker of ICC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma tumor burden classification regression tree model define prognostic groups resection background tumor burden important factor defining prognosis among patients primary secondary liver cancers although eighth edition american joint committee cancer staging system changed criteria staging patients intrahepatic cholangiocarcinoma better define effect tumor burden prognosis impact intrahepatic cholangiocarcinoma tumor burden overall survival examined using machine learning tool methods patients underwent resection intrahepatic cholangiocarcinoma 1 14 participating international hospitals 1990 2015 identified classical survival models classification regression tree model used identify groups patients homogeneous risk death investigate hierarchical association variables overall survival results among 1 116 patients included analysis tumor size 5 cm 447 40 1 patients 5 cm 669 59 9 patients although 82 9 n 926 patients single intrahepatic cholangiocarcinoma 9 9 n 110 7 2 n 80 patients 2 3 tumors respectively patients intrahepatic cholangiocarcinoma tumors 5 cm 5 cm 5 year overall survival 51 7 32 6 respectively p 0 001 five year overall survival decreased 44 6 among patients single intrahepatic cholangiocarcinoma 28 1 14 2 among patients 2 3 intrahepatic cholangiocarcinomas respectively p 0 001 among combinations tumor size intrahepatic cholangiocarcinoma tumor number used estimate tumor burden logarithmic transformation tumor size log tumor size intrahepatic cholangiocarcinoma tumor number highest concordance index classification regression tree model identified 8 classes patients homogeneous risk death illustrating hierarchical relationship tumor burden log tumor size number intrahepatic cholangiocarcinomas factors associated prognosis conclusion intrahepatic cholangiocarcinoma tumor size number demonstrated strong nonlinear association survival resection intrahepatic cholangiocarcinoma log model classification regression tree derived tumor burden score may better tool estimate prognosis patients undergoing curative intent resection intrahepatic cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Intrahepatic Cholangiocarcinoma Tumor Burden: A Classification And Regression Tree Model To Define Prognostic Groups After Resection","Abstract":"Background: Tumor burden is an important factor in defining prognosis among patients with primary and secondary liver cancers. Although the eighth edition of the American Joint Committee on Cancer staging system has changed the criteria for staging patients with intrahepatic cholangiocarcinoma to better define the effect of tumor burden on prognosis, the impact of intrahepatic cholangiocarcinoma tumor burden on overall survival has not been examined using a machine-learning tool. \r\n\r\n Methods: Patients who underwent resection of intrahepatic cholangiocarcinoma at 1 of 14 participating international hospitals between 1990 and 2015 were identified. Classical survival models and the Classification and Regression Tree model were used to identify groups of patients with a homogeneous risk of death and investigate the hierarchical association between variables and overall survival. \r\n\r\n Results: Among 1,116 patients included in the analysis, tumor size was ≤5 cm in 447 (40.1%) patients and >5 cm in 669 (59.9%) patients. Although 82.9% (n = 926) of patients had a single intrahepatic cholangiocarcinoma, 9.9% (n = 110) and 7.2% (n = 80) of patients had 2 and ≥3 tumors, respectively. Patients with intrahepatic cholangiocarcinoma tumors ≤5 cm and >5 cm had a 5-year overall survival of 51.7% and 32.6%, respectively (P < 0.001). Five-year overall survival decreased from 44.6% among patients with a single intrahepatic cholangiocarcinoma to 28.1% and 14.2% among patients with 2 and ≥3 intrahepatic cholangiocarcinomas, respectively (P < 0.001). Among the combinations of tumor size and intrahepatic cholangiocarcinoma tumor number used to estimate tumor burden, logarithmic transformation of tumor size (log tumor size) and intrahepatic cholangiocarcinoma tumor number had the highest concordance index. The Classification and Regression Tree model identified 8 classes of patients with a homogeneous risk of death, illustrating the hierarchical relationship between tumor burden (log tumor size and number of intrahepatic cholangiocarcinomas) and other factors associated with prognosis. \r\n\r\n Conclusion: Intrahepatic cholangiocarcinoma tumor size and number demonstrated a strong nonlinear association with survival after resection of intrahepatic cholangiocarcinoma. A log-model Classification and Regression Tree-derived tumor burden score may be a better tool to estimate prognosis of patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Intrahepatic Cholangiocarcinoma Tumor Burden: A Classification And Regression Tree Model To Define Prognostic Groups After Resection Background: Tumor burden is an important factor in defining prognosis among patients with primary and secondary liver cancers. Although the eighth edition of the American Joint Committee on Cancer staging system has changed the criteria for staging patients with intrahepatic cholangiocarcinoma to better define the effect of tumor burden on prognosis, the impact of intrahepatic cholangiocarcinoma tumor burden on overall survival has not been examined using a machine-learning tool. \r\n\r\n Methods: Patients who underwent resection of intrahepatic cholangiocarcinoma at 1 of 14 participating international hospitals between 1990 and 2015 were identified. Classical survival models and the Classification and Regression Tree model were used to identify groups of patients with a homogeneous risk of death and investigate the hierarchical association between variables and overall survival. \r\n\r\n Results: Among 1,116 patients included in the analysis, tumor size was ≤5 cm in 447 (40.1%) patients and >5 cm in 669 (59.9%) patients. Although 82.9% (n = 926) of patients had a single intrahepatic cholangiocarcinoma, 9.9% (n = 110) and 7.2% (n = 80) of patients had 2 and ≥3 tumors, respectively. Patients with intrahepatic cholangiocarcinoma tumors ≤5 cm and >5 cm had a 5-year overall survival of 51.7% and 32.6%, respectively (P < 0.001). Five-year overall survival decreased from 44.6% among patients with a single intrahepatic cholangiocarcinoma to 28.1% and 14.2% among patients with 2 and ≥3 intrahepatic cholangiocarcinomas, respectively (P < 0.001). Among the combinations of tumor size and intrahepatic cholangiocarcinoma tumor number used to estimate tumor burden, logarithmic transformation of tumor size (log tumor size) and intrahepatic cholangiocarcinoma tumor number had the highest concordance index. The Classification and Regression Tree model identified 8 classes of patients with a homogeneous risk of death, illustrating the hierarchical relationship between tumor burden (log tumor size and number of intrahepatic cholangiocarcinomas) and other factors associated with prognosis. \r\n\r\n Conclusion: Intrahepatic cholangiocarcinoma tumor size and number demonstrated a strong nonlinear association with survival after resection of intrahepatic cholangiocarcinoma. A log-model Classification and Regression Tree-derived tumor burden score may be a better tool to estimate prognosis of patients undergoing curative-intent resection of intrahepatic cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"hepatitis c risk nonhepatic malignancies non editable google scholar","probabilities":0.9799733,"Title":"Hepatitis C And Risk Of Nonhepatic Malignancies","Abstract":"Non-editable","Source":"Google Scholar","category":"HUMAN","training_data":"Hepatitis C And Risk Of Nonhepatic Malignancies Non-editable Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"relationship daily habits risk death patients biliary tract cancer large scale cohort study japan objective biliary tract cancer one deadliest diseases east asia death due disease comprises 5 total cancer deaths japan study conducted evaluate relationship biliary tract cancer daily habits using data japan collaborative cohort study evaluation cancer risk sponsored japanese ministry education jacc study methods jacc study cohort 110 792 subjects aged 40 79 19 prefectures japan completed baseline survey 1988 1990 subjects followed 2009 endpoint present study death due biliary tract cancer coded c22 1 intrahepatic bile duct carcinoma ccc c23 malignant neoplasm gallbladder gb cancer c24 malignant neoplasm unspecified parts biliary tract bd cancer international classification diseases related health problems 10th revision icd 10 hazard ratio hr biliary tract cancer mortality smoking drinking habits high intake fatty food body mass index job category office job field work others evaluated results considered significant 5 critical level results high intake fatty food smoking habit field work showed significant positive association death female patients due bd cancer females hr 1 87 95 confidence interval ci 1 03 3 39 hr 1 56 95 ci 1 02 2 39 hr 2 23 95 ci 1 03 4 84 respectively significant relationship observed daily habits death due ccc gb cancer conclusion high intake fatty food often key factor risk death due biliary tract cancer well known smoking cause various cancers findings support results previous research moreover results suggest occupational differences may effect mortality female patients biliary tract cancer therefore detailed analysis job category required meaningful interpretation data google scholar","probabilities":0.9799733,"Title":"Relationship Between Daily Habits And Risk Of Death In Patients With Biliary Tract Cancer: A Large-Scale Cohort Study In Japan","Abstract":"Objective: Biliary tract cancer is one of the deadliest diseases in East Asia. Death due to this disease comprises 5% of total cancer deaths in Japan. This study was conducted to evaluate the relationship between biliary tract cancer and daily habits using data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Japanese Ministry of Education (JACC study).\nMethods: In the JACC study, a cohort of 110,792 subjects aged 40-79 from 19 prefectures in Japan completed the baseline survey during 1988-1990. The subjects were followed up until 2009. The endpoint for the present study was death due to biliary tract cancer, coded as C22.1 (intrahepatic bile duct carcinoma, CCC), C23 (malignant neoplasm of the gallbladder, GB cancer), and C24 (malignant neoplasm of other and unspecified parts of the biliary tract, BD cancer) in the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The hazard ratio (HR) of biliary tract cancer mortality for smoking and drinking habits, high intake of fatty food, body mass index, and the job category (office job, field work, and others) was evaluated. All results were considered to be significant at the 5% critical level.\nResults: High intake of fatty food, smoking habit, and field work showed a significant positive association with death in female patients due to BD cancer in females [HR = 1.87, 95% confidence interval (CI): 1.03-3.39; HR = 1.56, 95% CI: 1.02-2.39; and HR = 2.23, 95% CI: 1.03-4.84, respectively]. No significant relationship was observed between daily habits and death due to CCC and GB cancer.\nConclusion: High intake of fatty food is often a key factor in the risk of death due to biliary tract cancer, and it is well known that smoking can cause various other cancers. Our findings support the results of a previous research. Moreover, our results suggest that occupational differences may have an effect on mortality in female patients with biliary tract cancer. Therefore, a more detailed analysis of the job category is required for a more meaningful interpretation of the data.","Source":"Google Scholar","category":"HUMAN","training_data":"Relationship Between Daily Habits And Risk Of Death In Patients With Biliary Tract Cancer: A Large-Scale Cohort Study In Japan Objective: Biliary tract cancer is one of the deadliest diseases in East Asia. Death due to this disease comprises 5% of total cancer deaths in Japan. This study was conducted to evaluate the relationship between biliary tract cancer and daily habits using data from the Japan Collaborative Cohort Study for Evaluation of Cancer Risk sponsored by the Japanese Ministry of Education (JACC study).\nMethods: In the JACC study, a cohort of 110,792 subjects aged 40-79 from 19 prefectures in Japan completed the baseline survey during 1988-1990. The subjects were followed up until 2009. The endpoint for the present study was death due to biliary tract cancer, coded as C22.1 (intrahepatic bile duct carcinoma, CCC), C23 (malignant neoplasm of the gallbladder, GB cancer), and C24 (malignant neoplasm of other and unspecified parts of the biliary tract, BD cancer) in the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10). The hazard ratio (HR) of biliary tract cancer mortality for smoking and drinking habits, high intake of fatty food, body mass index, and the job category (office job, field work, and others) was evaluated. All results were considered to be significant at the 5% critical level.\nResults: High intake of fatty food, smoking habit, and field work showed a significant positive association with death in female patients due to BD cancer in females [HR = 1.87, 95% confidence interval (CI): 1.03-3.39; HR = 1.56, 95% CI: 1.02-2.39; and HR = 2.23, 95% CI: 1.03-4.84, respectively]. No significant relationship was observed between daily habits and death due to CCC and GB cancer.\nConclusion: High intake of fatty food is often a key factor in the risk of death due to biliary tract cancer, and it is well known that smoking can cause various other cancers. Our findings support the results of a previous research. Moreover, our results suggest that occupational differences may have an effect on mortality in female patients with biliary tract cancer. Therefore, a more detailed analysis of the job category is required for a more meaningful interpretation of the data. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"coffee consumption risk biliary tract cancers liver cancer dose response meta analysis prospective cohort studies background meta analysis conducted summarize evidence prospective cohort case control studies regarding association coffee intake biliary tract cancer btc liver cancer risk methods eligible studies identified searches pubmed embase databases earliest available online indexing year march 2017 dose response relationship assessed restricted cubic spline model multivariate random effect meta regression stratified subgroup analysis smoking status hepatitis performed identify potential confounding factors results identified five studies btc risk 13 liver cancer risk eligible meta analysis linear dose response meta analysis show significant association coffee consumption btc risk however evidence inverse correlation coffee consumption liver cancer risk association consistent throughout various potential confounding factors explored including smoking status hepatitis etc increasing coffee consumption one cup per day associated 15 reduction liver cancer risk rr 0 85 95 ci 0 82 0 88 conclusions findings suggest increased coffee consumption associated decreased risk liver cancer btc pubmed","probabilities":0.9799733,"Title":"Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies","Abstract":"BACKGROUND: A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. METHODS: Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. RESULTS: We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose-response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). CONCLUSIONS: The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC.","Source":"PubMed","category":"HUMAN","training_data":"Coffee Consumption and Risk of Biliary Tract Cancers and Liver Cancer: A Dose-Response Meta-Analysis of Prospective Cohort Studies BACKGROUND: A meta-analysis was conducted to summarize the evidence from prospective cohort and case-control studies regarding the association between coffee intake and biliary tract cancer (BTC) and liver cancer risk. METHODS: Eligible studies were identified by searches of PubMed and EMBASE databases from the earliest available online indexing year to March 2017. The dose-response relationship was assessed by a restricted cubic spline model and multivariate random-effect meta-regression. A stratified and subgroup analysis by smoking status and hepatitis was performed to identify potential confounding factors. RESULTS: We identified five studies on BTC risk and 13 on liver cancer risk eligible for meta-analysis. A linear dose-response meta-analysis did not show a significant association between coffee consumption and BTC risk. However, there was evidence of inverse correlation between coffee consumption and liver cancer risk. The association was consistent throughout the various potential confounding factors explored including smoking status, hepatitis, etc. Increasing coffee consumption by one cup per day was associated with a 15% reduction in liver cancer risk (RR 0.85; 95% CI 0.82 to 0.88). CONCLUSIONS: The findings suggest that increased coffee consumption is associated with decreased risk of liver cancer, but not BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"elevated platelet distribution width predicts poor prognosis hilar cholangiocarcinoma although platelet distribution width pdw reported reliable predictor prognosis several types cancer knowledge prognostic value pdw hilar cholangiocarcinoma hc studied aim study investigate prognostic value pdw hc patients retrospective analysis 292 consecutively recruited hc patients undergoing radical resection least 5 year follow optimal cutoff value pdw determined receiver operating characteristic roc curve survival analysis kaplan meier method difference clinico pathologic variables survival evaluated log rank analysis multivariate analysis identified independent prognostic risk factors overall survival os roc curve analysis suggested optimal cutoff value pdw 16 55 significant associations high pdw high white blood cell p 001 high neutril lymph ratio p 001 multivariate analysis pdw independent prognostic factor overall survival hr 2 521 95 ci 1 832 3 470 p 001 conclusions findings indicate pdw may clinical significance predicting os surgery hc patients pubmed","probabilities":0.962963,"Title":"Elevated platelet distribution width predicts poor prognosis in hilar cholangiocarcinoma","Abstract":"Although the platelet distribution width (PDW) has been reported as a reliable predictor of prognosis in several types of cancer, to our knowledge the prognostic value of PDW in hilar cholangiocarcinoma (HC) has not been studied. The aim of the study was to investigate the prognostic value of PDW in HC patients. A retrospective analysis of 292 consecutively recruited HC patients undergoing radical resection with at least a 5-year follow-up. The optimal cutoff value of PDW was determined by receiver operating characteristic (ROC) curve. Survival analysis by the Kaplan-Meier method and the difference between the clinico-pathologic variables and survival was evaluated by log-rank analysis. Multivariate analysis identified independent prognostic risk factors of overall survival (OS). ROC curve analysis suggested that the optimal cutoff value for the PDW was 16.55. There were significant associations of high PDW with high white blood cell (P < .001) and high neutril-to-lymph ratio (P < .001). In a multivariate analysis, the PDW was an independent prognostic factor for overall survival (HR = 2.521, 95% CI 1.832-3.470, P < .001). In conclusions, our findings indicate that PDW may have clinical significance in predicting OS after surgery in HC patients.","Source":"PubMed","category":"HUMAN","training_data":"Elevated platelet distribution width predicts poor prognosis in hilar cholangiocarcinoma Although the platelet distribution width (PDW) has been reported as a reliable predictor of prognosis in several types of cancer, to our knowledge the prognostic value of PDW in hilar cholangiocarcinoma (HC) has not been studied. The aim of the study was to investigate the prognostic value of PDW in HC patients. A retrospective analysis of 292 consecutively recruited HC patients undergoing radical resection with at least a 5-year follow-up. The optimal cutoff value of PDW was determined by receiver operating characteristic (ROC) curve. Survival analysis by the Kaplan-Meier method and the difference between the clinico-pathologic variables and survival was evaluated by log-rank analysis. Multivariate analysis identified independent prognostic risk factors of overall survival (OS). ROC curve analysis suggested that the optimal cutoff value for the PDW was 16.55. There were significant associations of high PDW with high white blood cell (P < .001) and high neutril-to-lymph ratio (P < .001). In a multivariate analysis, the PDW was an independent prognostic factor for overall survival (HR = 2.521, 95% CI 1.832-3.470, P < .001). In conclusions, our findings indicate that PDW may have clinical significance in predicting OS after surgery in HC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"overall survival peri hilar cholangiocarcinoma r1 resection curative intent compared primary endoscopic therapy background objectives patients peri hilar cholangiocarcinoma undergo r1 resection curative intent improved survival compared patients resected methods review prospective hepatobiliary database identified 130 patients survival compared using log rank test results seventy nine patients 61 resected 51 49 patients forty two patients 54 r0 resection difference mean age 69 vs 67 p 0 8 bmi 27 8 vs 27 9 p 1 0 gender 73 vs 43 male p 0 1 presence jaundice 77 vs 64 p 0 5 vascular involvement pre operative imaging 77 vs 64 p 0 5 stent 73 1 vs 64 3 p 0 72 lobar atrophy 27 vs 7 p 0 2 resected versus non resected patients patients underwent chemotherapy radiation therapy median follow 35 6 months median osl peri hilar patients 16 2 months 95 ci 11 2 23 4 median os resected patients 18 9 months 95 ci 12 5 24 7 versus 5 0 months 95 ci 0 6 9 patients resected p 0 001 pre operative predictor os resection p 0 041 vascular invasion lobar atrophy stent placement statistically significant predictors conclusion overall survival improved patients undergoing r1 resection multi modality therapy compared patients resected pubmed","probabilities":0.9799733,"Title":"Overall survival peri-hilar cholangiocarcinoma: R1 resection with curative intent compared to primary endoscopic therapy","Abstract":"BACKGROUND AND OBJECTIVES: Patients with peri-hilar cholangiocarcinoma who undergo R1 resection with curative intent will have an improved survival compared to patients who were not resected. METHODS: Review of a prospective hepatobiliary database identified 130 patients. Survival was compared using the log-rank test. RESULTS: Seventy-nine patients (61%) were resected while 51 (49%) patients were not. Forty-two patients (54%) had an R0 resection. There was no difference in mean age (69 vs. 67; P = 0.8), BMI (27.8 vs. 27.9; P = 1.0), gender (73% vs. 43% male; P = 0.1), presence of jaundice (77% vs. 64%; P = 0.5), vascular involvement on pre operative imaging (77% vs. 64%; P = 0.5), stent (73.1% vs. 64.3%; P = 0.72), and lobar atrophy (27% vs. 7%, P = 0.2) in the resected versus non-resected patients. All patients underwent chemotherapy and/or radiation therapy. After a median follow up of 35.6 months the median OSl for all peri-hilar patients was 16.2 months (95% CI = 11.2-23.4). The median OS for resected patients was 18.9 months (95% CI = 12.5-24.7) versus 5.0 months (95% CI = 0-6.9) for patients not resected (P < 0.001). The only pre-operative predictor of OS was resection (P = 0.041). Vascular invasion, lobar atrophy, and stent placement were not statistically significant predictors. CONCLUSION: Overall survival is improved in patients undergoing R1 resection and multi-modality therapy compared to patients not resected.","Source":"PubMed","category":"HUMAN","training_data":"Overall survival peri-hilar cholangiocarcinoma: R1 resection with curative intent compared to primary endoscopic therapy BACKGROUND AND OBJECTIVES: Patients with peri-hilar cholangiocarcinoma who undergo R1 resection with curative intent will have an improved survival compared to patients who were not resected. METHODS: Review of a prospective hepatobiliary database identified 130 patients. Survival was compared using the log-rank test. RESULTS: Seventy-nine patients (61%) were resected while 51 (49%) patients were not. Forty-two patients (54%) had an R0 resection. There was no difference in mean age (69 vs. 67; P = 0.8), BMI (27.8 vs. 27.9; P = 1.0), gender (73% vs. 43% male; P = 0.1), presence of jaundice (77% vs. 64%; P = 0.5), vascular involvement on pre operative imaging (77% vs. 64%; P = 0.5), stent (73.1% vs. 64.3%; P = 0.72), and lobar atrophy (27% vs. 7%, P = 0.2) in the resected versus non-resected patients. All patients underwent chemotherapy and/or radiation therapy. After a median follow up of 35.6 months the median OSl for all peri-hilar patients was 16.2 months (95% CI = 11.2-23.4). The median OS for resected patients was 18.9 months (95% CI = 12.5-24.7) versus 5.0 months (95% CI = 0-6.9) for patients not resected (P < 0.001). The only pre-operative predictor of OS was resection (P = 0.041). Vascular invasion, lobar atrophy, and stent placement were not statistically significant predictors. CONCLUSION: Overall survival is improved in patients undergoing R1 resection and multi-modality therapy compared to patients not resected. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors overall survival patients unresectable intrahepatic cholangiocarcinoma treated means yttrium 90 radioembolization results therapy na ve patients introduction investigate prognostic factors unresectable intrahepatic cholangiocarcinoma icc therapy na ve patients yttrium 90 y 90 radioembolization re therapy materials methods 2005 2016 21 patients icc treated y 90 re survival data analyzed patients stratified response assessed response evaluation criteria solid tumors recist criteria result overall median survival 15 months survival significantly p 0 009 prolonged patients tumor burden 25 n 8 os 37 5 months versus tumor burden 25 50 n 13 os 15 months variables tumor morphology infiltrative vs peripheral tumor distribution solitary vs multifocal lobes involved unilobar vs bilobar fdg pet status fdg avid vs non avid re treatment sessions 1 session vs 2 sessions metastases metastasis vs metastasis recist criteria significant impact survival conclusion tumor burden represents key prognostic factor survival therapy na ve patients unresectable icc treated y 90 re therapy pubmed","probabilities":0.9799733,"Title":"Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in Therapy-Naïve Patients","Abstract":"INTRODUCTION: To investigate prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) therapy-naïve patients after yttrium-90 (Y-90) radioembolization (RE) therapy. MATERIALS AND METHODS: Between 2005 and 2016, 21 patients with ICC were treated with Y-90 RE only and their survival data were analyzed. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULT: The overall median survival was 15 months. Survival was significantly (p = 0.009) prolonged in patients with tumor burden of ≤ 25% (n = 8, OS 37.5 months) versus those with a tumor burden of 25-50% (n = 13, OS 15 months). The other variables: tumor morphology (infiltrative vs. peripheral), tumor distribution (solitary vs. multifocal), lobes involved (unilobar vs. bilobar), FDG PET status (FDG avid vs. non-avid), RE treatment sessions (1 session vs. 2 sessions), metastases (metastasis vs. no metastasis) and RECIST criteria, had no significant impact on survival. CONCLUSION: Tumor burden represents a key prognostic factor of survival in therapy-naïve patients with unresectable ICC treated with Y-90 RE therapy only.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Factors in Overall Survival of Patients with Unresectable Intrahepatic Cholangiocarcinoma Treated by Means of Yttrium-90 Radioembolization: Results in Therapy-Naïve Patients INTRODUCTION: To investigate prognostic factors in unresectable intrahepatic cholangiocarcinoma (ICC) therapy-naïve patients after yttrium-90 (Y-90) radioembolization (RE) therapy. MATERIALS AND METHODS: Between 2005 and 2016, 21 patients with ICC were treated with Y-90 RE only and their survival data were analyzed. Patients were stratified and response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. RESULT: The overall median survival was 15 months. Survival was significantly (p = 0.009) prolonged in patients with tumor burden of ≤ 25% (n = 8, OS 37.5 months) versus those with a tumor burden of 25-50% (n = 13, OS 15 months). The other variables: tumor morphology (infiltrative vs. peripheral), tumor distribution (solitary vs. multifocal), lobes involved (unilobar vs. bilobar), FDG PET status (FDG avid vs. non-avid), RE treatment sessions (1 session vs. 2 sessions), metastases (metastasis vs. no metastasis) and RECIST criteria, had no significant impact on survival. CONCLUSION: Tumor burden represents a key prognostic factor of survival in therapy-naïve patients with unresectable ICC treated with Y-90 RE therapy only. PubMed","prediction_labels":"HUMAN"},{"cleaned":"combination anti l1 cell adhesion molecule antibody gemcitabine cisplatin improves therapeutic response intrahepatic cholangiocarcinoma cholangiocarcinoma poor prognosis refractory conventional chemotherapy radiation therapy improving survival patients advanced cholangiocarcinoma urgently requires development new effective targeted therapies combination chemotherapy previously developed human monoclonal antibody mab ab417 binds human mouse l1 cell adhesion molecule l1cam high affinities present study observed ab417 exhibited tumor targeting ability biodistribution studies dose dependent tumor growth inhibition intrahepatic cholangiocarcinoma choi ck xenograft mouse model regarding mechanism action ab417 internalized tumor cells thereby regulated membrane l1cam inhibited tumor growth reducing tumor cell proliferation vivo gemcitabine inhibited tumor growth dose dependent manner choi ck xenograft model however cisplatin inhibited tumor growth moderately dose dependent way suggesting tumors may developed resistance apoptosis induced cisplatin combined treatment ab417 gemcitabine cisplatin exerted enhanced tumor growth inhibition compared treatment antibody drug alone results suggest ab417 combination chemotherapy may potential new therapeutic regimen cholangiocarcinoma study first show enhanced therapeutic effect therapeutic antibody targeting l1cam combination chemotherapy cholangiocarcinoma models stn","probabilities":0.9467213,"Title":"Combination Of Anti-L1 Cell Adhesion Molecule Antibody And Gemcitabine Or Cisplatin Improves The Therapeutic Response Of Intrahepatic Cholangiocarcinoma","Abstract":"Cholangiocarcinoma has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Improving survival of patients with advanced cholangiocarcinoma urgently requires the development of new effective targeted therapies in combination with chemotherapy. We previously developed a human monoclonal antibody (mAb) Ab417 that binds to both the human and mouse L1 cell adhesion molecule (L1CAM) with high affinities. In the present study, we observed that Ab417 exhibited tumor targeting ability in biodistribution studies and dose-dependent tumor growth inhibition in an intrahepatic cholangiocarcinoma (Choi-CK) xenograft mouse model. Regarding the mechanism of action, Ab417 was internalized into the tumor cells and thereby down-regulated membrane L1CAM, and inhibited tumor growth by reducing tumor cell proliferation in vivo. Gemcitabine inhibited the tumor growth in a dose-dependent manner in the Choi-CK xenograft model. However, cisplatin inhibited the tumor growth moderately and not in a dose-dependent way, suggesting that the tumors may have developed resistance to apoptosis induced by cisplatin. Combined treatment with Ab417 and gemcitabine or cisplatin exerted enhanced tumor growth inhibition compared to treatment with antibody or drug alone. The results suggest that Ab417 in combination with chemotherapy may have potential as a new therapeutic regimen for cholangiocarcinoma. Our study is the first to show an enhanced therapeutic effect of a therapeutic antibody targeting L1CAM in combination with chemotherapy in cholangiocarcinoma models.","Source":"STN","category":"ANIMAL","training_data":"Combination Of Anti-L1 Cell Adhesion Molecule Antibody And Gemcitabine Or Cisplatin Improves The Therapeutic Response Of Intrahepatic Cholangiocarcinoma Cholangiocarcinoma has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Improving survival of patients with advanced cholangiocarcinoma urgently requires the development of new effective targeted therapies in combination with chemotherapy. We previously developed a human monoclonal antibody (mAb) Ab417 that binds to both the human and mouse L1 cell adhesion molecule (L1CAM) with high affinities. In the present study, we observed that Ab417 exhibited tumor targeting ability in biodistribution studies and dose-dependent tumor growth inhibition in an intrahepatic cholangiocarcinoma (Choi-CK) xenograft mouse model. Regarding the mechanism of action, Ab417 was internalized into the tumor cells and thereby down-regulated membrane L1CAM, and inhibited tumor growth by reducing tumor cell proliferation in vivo. Gemcitabine inhibited the tumor growth in a dose-dependent manner in the Choi-CK xenograft model. However, cisplatin inhibited the tumor growth moderately and not in a dose-dependent way, suggesting that the tumors may have developed resistance to apoptosis induced by cisplatin. Combined treatment with Ab417 and gemcitabine or cisplatin exerted enhanced tumor growth inhibition compared to treatment with antibody or drug alone. The results suggest that Ab417 in combination with chemotherapy may have potential as a new therapeutic regimen for cholangiocarcinoma. Our study is the first to show an enhanced therapeutic effect of a therapeutic antibody targeting L1CAM in combination with chemotherapy in cholangiocarcinoma models. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic importance lymphovascular invasion cholangiocarcinoma cystic duct new selection criterion adjuvant therapy objective criteria selecting patients receive adjuvant chemotherapy cases resected intrahepatic hilar cholangiocarcinoma cc lacking clinicians advocate provision adjuvant therapy patients lymph node ln positive disease however nodal assessment often inadequate aim study identify surrogate criterion based primary tumour characteristics methods patients underwent resection hilar intrahepatic cc single institution january 2000 september 2009 identified prospectively maintained database pathological factors recorded primary outcome assessed overall survival os results total 69 patients underwent resection hilar n 34 intrahepatic n 35 cc median age 66 years 27 patients 39 male median follow 22 months median os 17 months median tumour size 5 cm overall 23 patients positive resection margin 44 perineural invasion 32 lymphovascular invasion lvi 25 positive lns median number lns removed two median number positive lns zero presence lvi associated reduced os 11 9 months vs 23 1 months p 0 023 accounting adverse tumour factors presence lvi persisted negative prognostic factor os multivariate cox regression conclusions patients undergone resection hilar intrahepatic cc presence lvi strongly associated reduced os thus finding lvi may potentially used criterion selection patients adjuvant chemotherapy pubmed","probabilities":0.9799733,"Title":"The prognostic importance of lymphovascular invasion in cholangiocarcinoma above the cystic duct: a new selection criterion for adjuvant therapy?","Abstract":"OBJECTIVE: Criteria for selecting patients to receive adjuvant chemotherapy in cases of resected intrahepatic or hilar cholangiocarcinoma (CC) are lacking. Some clinicians advocate the provision of adjuvant therapy in patients with lymph node (LN)-positive disease; however, nodal assessment is often inadequate. The aim of this study was to identify a surrogate criterion based on primary tumour characteristics. METHODS: All patients who underwent resection for hilar or intrahepatic CC at a single institution between January 2000 and September 2009 were identified from a prospectively maintained database. Pathological factors were recorded. The primary outcome assessed was overall survival (OS). RESULTS: In total, 69 patients underwent resection for hilar (n=34) or intrahepatic (n=35) CC. Their median age was 66 years and 27 patients (39%) were male. Median follow-up was 22 months and median OS was 17 months. Median tumour size was 5 cm. Overall, 23% of patients had a positive resection margin, 44% had perineural invasion, 32% had lymphovascular invasion (LVI) and 25% had positive LNs. The median number of LNs removed was two and the median number of positive LNs was zero. The presence of LVI was associated with reduced OS (11.9 months vs. 23.1 months; P=0.023). After accounting for all other adverse tumour factors, the presence of LVI persisted as the only negative prognostic factor for OS on multivariate Cox regression. CONCLUSIONS: In patients who had undergone resection of hilar or intrahepatic CC, the presence of LVI was strongly associated with reduced OS. Thus the finding of LVI may potentially be used as a criterion in the selection of patients for adjuvant chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"The prognostic importance of lymphovascular invasion in cholangiocarcinoma above the cystic duct: a new selection criterion for adjuvant therapy? OBJECTIVE: Criteria for selecting patients to receive adjuvant chemotherapy in cases of resected intrahepatic or hilar cholangiocarcinoma (CC) are lacking. Some clinicians advocate the provision of adjuvant therapy in patients with lymph node (LN)-positive disease; however, nodal assessment is often inadequate. The aim of this study was to identify a surrogate criterion based on primary tumour characteristics. METHODS: All patients who underwent resection for hilar or intrahepatic CC at a single institution between January 2000 and September 2009 were identified from a prospectively maintained database. Pathological factors were recorded. The primary outcome assessed was overall survival (OS). RESULTS: In total, 69 patients underwent resection for hilar (n=34) or intrahepatic (n=35) CC. Their median age was 66 years and 27 patients (39%) were male. Median follow-up was 22 months and median OS was 17 months. Median tumour size was 5 cm. Overall, 23% of patients had a positive resection margin, 44% had perineural invasion, 32% had lymphovascular invasion (LVI) and 25% had positive LNs. The median number of LNs removed was two and the median number of positive LNs was zero. The presence of LVI was associated with reduced OS (11.9 months vs. 23.1 months; P=0.023). After accounting for all other adverse tumour factors, the presence of LVI persisted as the only negative prognostic factor for OS on multivariate Cox regression. CONCLUSIONS: In patients who had undergone resection of hilar or intrahepatic CC, the presence of LVI was strongly associated with reduced OS. Thus the finding of LVI may potentially be used as a criterion in the selection of patients for adjuvant chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect demographics socio economic factors survival unresectable intrahepatic cholangiocarcinoma surveillance epidemiology end results seer population study background investigate long term survival patients unresectable icc based socio demographic factors large scale population study methods us surveillance epidemiology end results seer database queried patients icc amenable cancer directed surgery radiation diagnosed 2000 2010 mean overall survival os stratified according patient characteristics including gender age diagnosis ethnicity geographic location income education urbanization kaplan meier estimation cox proportional hazard models used survival analysis assess independent prognostic factors os results 63 434 newly diagnosed liver cancer patients 5 409 icc median age 71 yrs 50 male os significantly correlated age diagnosis 70 vs 70 yrs 24 0 vs 17 5 months p 001 ethnicity white black american indian asian pacific islander 20 6 18 6 18 2 18 3 months p 001 geographic location east northern plains southwest pacific coast alaska 20 5 23 4 17 5 20 7 30 5 months p 03 income median household income 45k vs 45k year 17 6 vs 21 5 months p 001 education bachelor degree 25 vs 25 19 2 vs 21 9 months p 001 degree urbanization county population 50k vs 50k 21 4 vs 14 3 months p 007 conclusions unresectable icc socio demographic factors including age 70 white ethnicity alaska urban settings higher income education levels significantly correlated prolonged os population based study google scholar","probabilities":0.9799733,"Title":"The Effect Of Demographics And Socio-Economic Factors On Survival In Unresectable Intrahepatic Cholangiocarcinoma: A Surveillance Epidemiology And End Results (Seer) Population Study","Abstract":"Background: To investigate long-term survival in patients with unresectable ICC based on socio-demographic factors in a large-scale population study. Methods: The US Surveillance, Epidemiology and End Results (SEER) database was queried for patients with ICC not amenable to cancer-directed surgery/radiation diagnosed from 2000-2010. Mean overall survival (OS) was stratified according to patient characteristics including gender, age at diagnosis, ethnicity, geographic location, income, education, and urbanization. Kaplan-Meier estimation and Cox proportional hazard models were used for survival analysis and to assess independent prognostic factors for OS. Results: Of 63,434 newly diagnosed liver cancer patients, 5,409 had ICC, median age 71 yrs, 50% male. OS was significantly correlated with age at diagnosis (< 70 vs. ≥ 70 yrs, 24.0 vs. 17.5 months, p < .001), ethnicity (white, black, American Indian, Asian/Pacific Islander; 20.6, 18.6, 18.2, 18.3 months; p < .001), geographic location (East, Northern Plains, Southwest, Pacific Coast, Alaska; 20.5, 23.4, 17.5, 20.7, 30.5 months; p = .03), income (median household income ≥ $45k vs. < $45k/year, 17.6 vs. 21.5 months, p < .001), education (% bachelor degree or above, ≥ 25% vs. < 25%, 19.2 vs. 21.9 months, p < .001) and degree of urbanization (county population ≥ 50k vs. < 50k, 21.4 vs. 14.3 months, p = .007). Conclusions: In unresectable ICC, socio-demographic factors including age <70, white ethnicity, those from Alaska, urban settings, and higher income & education levels were significantly correlated with prolonged OS in a population-based study.","Source":"Google Scholar","category":"HUMAN","training_data":"The Effect Of Demographics And Socio-Economic Factors On Survival In Unresectable Intrahepatic Cholangiocarcinoma: A Surveillance Epidemiology And End Results (Seer) Population Study Background: To investigate long-term survival in patients with unresectable ICC based on socio-demographic factors in a large-scale population study. Methods: The US Surveillance, Epidemiology and End Results (SEER) database was queried for patients with ICC not amenable to cancer-directed surgery/radiation diagnosed from 2000-2010. Mean overall survival (OS) was stratified according to patient characteristics including gender, age at diagnosis, ethnicity, geographic location, income, education, and urbanization. Kaplan-Meier estimation and Cox proportional hazard models were used for survival analysis and to assess independent prognostic factors for OS. Results: Of 63,434 newly diagnosed liver cancer patients, 5,409 had ICC, median age 71 yrs, 50% male. OS was significantly correlated with age at diagnosis (< 70 vs. ≥ 70 yrs, 24.0 vs. 17.5 months, p < .001), ethnicity (white, black, American Indian, Asian/Pacific Islander; 20.6, 18.6, 18.2, 18.3 months; p < .001), geographic location (East, Northern Plains, Southwest, Pacific Coast, Alaska; 20.5, 23.4, 17.5, 20.7, 30.5 months; p = .03), income (median household income ≥ $45k vs. < $45k/year, 17.6 vs. 21.5 months, p < .001), education (% bachelor degree or above, ≥ 25% vs. < 25%, 19.2 vs. 21.9 months, p < .001) and degree of urbanization (county population ≥ 50k vs. < 50k, 21.4 vs. 14.3 months, p = .007). Conclusions: In unresectable ICC, socio-demographic factors including age <70, white ethnicity, those from Alaska, urban settings, and higher income & education levels were significantly correlated with prolonged OS in a population-based study. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"role non steroidal antiinflammatory drugs statins aetiology cholangiocarcinoma preliminary results case control study two uk centres introduction incidence cholangiocarcinoma increased worldwide mortality remaining high aetiology largely unknown aspirin non steroidal anti inflammatory drugs nsaids statins may protective growth cholangiocarcinoma cells inhibited vitro animal models nsaids block cox 2 enzyme also statins inhibit production intracellular mediators stimulating cell cycle epidemiological data area minimal studies specifically investigated aspirin statins western populations aim study investigate negative association medications development cholangiocarcinoma two centres uk methods cases cholangiocarcinoma identified norwich years 2004 2010 leicester year 2007 multi disciplinary team meeting cancer clinical databases used local hospitals inclusion required diagnostic evidence ct scans histology controls patients basal cell carcinomas treated dermatology departments case notes subjects reviewed obtain information use nsaids aspirin data analysed using unconditional logistic regression calculate ors 95 cis adjusted age gender results total 77 cases cholangiocarcinoma median age diagnosis 76 years range 41 96 years 51 men 251 controls identified patients radiological evidence cancer 29 histological confirmation 85 involving extrahepatic biliary system median survival patients 3 6 months iq range 0 9 8 0 months borderline statistically significant negative association aspirin use occurrence cholangiocarcinoma 0 55 95 ci 0 28 1 07 p 0 08 association nsaid use 0 49 95 ci 0 16 1 48 p 0 21 statins 0 71 95 ci 0 37 1 38 p 0 31 conclusion epidemiological data may support biological evidence aspirin protecting development cholangiocarcinoma work progressing identify subjects precisely define effect size aetiological work populations required determine association aspirin consistent although use currently measured aetiological studies cholangiocarcinoma google scholar","probabilities":1.0,"Title":"The Role Of Non-Steroidal Antiinflammatory Drugs And Statins In The Aetiology Of Cholangiocarcinoma: Preliminary Results From A Case-Control Study In Two Uk Centres","Abstract":"Introduction The incidence of cholangiocarcinoma has increased worldwide with the mortality remaining high. The aetiology is largely unknown but aspirin, non-steroidal anti-inflammatory drugs (NSAIDS) and statins may be protective. The growth of cholangiocarcinoma cells is inhibited in both in vitro and animal models by NSAIDs, which block the Cox-2 enzyme, and also statins inhibit the production of intracellular mediators stimulating the cell cycle. The epidemiological data in this area is minimal with no studies having specifically investigated aspirin or statins in western populations. The aim of this study was to investigate if there was a negative association between these medications and the development of cholangiocarcinoma in two centres in The UK.\nMethods Cases of cholangiocarcinoma were identified in Norwich (years 2004–2010) and Leicester (year 2007) from the multi-disciplinary team meeting cancer clinical databases used at the local hospitals. Inclusion required diagnostic evidence from CT scans and/or histology. Controls were patients with basal cell carcinomas treated in the dermatology departments. The case notes of all subjects were reviewed to obtain information on the use of NSAIDS and aspirin. Data were analysed using unconditional logistic regression to calculate ORs with 95% CIs, adjusted for age and gender.\nResults A total of 77 cases of cholangiocarcinoma (median age at diagnosis of 76 years, range 41–96 years, 51% men) and 251 controls were identified. All patients had radiological evidence of cancer and 29% had histological confirmation, with 85% involving the extrahepatic biliary system. The median survival of all patients was 3.6 months (IQ range 0.9–8.0 months). There was a borderline statistically significant negative association between aspirin use and the occurrence of cholangiocarcinoma (OR 0.55, 95% CI 0.28 to 1.07, p=0.08) but no association with NSAID use (OR 0.49, 95% CI 0.16 to 1.48 p=0.21) or statins (OR 0.71, 95% CI 0.37 to 1.38, p=0.31).\nConclusion This epidemiological data may support biological evidence for aspirin protecting against the development of cholangiocarcinoma. The work is progressing to identify further subjects to more precisely define the effect size. Aetiological work in other populations is required to determine if the association with aspirin is consistent although its use should currently be measured in aetiological studies of cholangiocarcinoma.","Source":"Google Scholar","category":"HUMAN","training_data":"The Role Of Non-Steroidal Antiinflammatory Drugs And Statins In The Aetiology Of Cholangiocarcinoma: Preliminary Results From A Case-Control Study In Two Uk Centres Introduction The incidence of cholangiocarcinoma has increased worldwide with the mortality remaining high. The aetiology is largely unknown but aspirin, non-steroidal anti-inflammatory drugs (NSAIDS) and statins may be protective. The growth of cholangiocarcinoma cells is inhibited in both in vitro and animal models by NSAIDs, which block the Cox-2 enzyme, and also statins inhibit the production of intracellular mediators stimulating the cell cycle. The epidemiological data in this area is minimal with no studies having specifically investigated aspirin or statins in western populations. The aim of this study was to investigate if there was a negative association between these medications and the development of cholangiocarcinoma in two centres in The UK.\nMethods Cases of cholangiocarcinoma were identified in Norwich (years 2004–2010) and Leicester (year 2007) from the multi-disciplinary team meeting cancer clinical databases used at the local hospitals. Inclusion required diagnostic evidence from CT scans and/or histology. Controls were patients with basal cell carcinomas treated in the dermatology departments. The case notes of all subjects were reviewed to obtain information on the use of NSAIDS and aspirin. Data were analysed using unconditional logistic regression to calculate ORs with 95% CIs, adjusted for age and gender.\nResults A total of 77 cases of cholangiocarcinoma (median age at diagnosis of 76 years, range 41–96 years, 51% men) and 251 controls were identified. All patients had radiological evidence of cancer and 29% had histological confirmation, with 85% involving the extrahepatic biliary system. The median survival of all patients was 3.6 months (IQ range 0.9–8.0 months). There was a borderline statistically significant negative association between aspirin use and the occurrence of cholangiocarcinoma (OR 0.55, 95% CI 0.28 to 1.07, p=0.08) but no association with NSAID use (OR 0.49, 95% CI 0.16 to 1.48 p=0.21) or statins (OR 0.71, 95% CI 0.37 to 1.38, p=0.31).\nConclusion This epidemiological data may support biological evidence for aspirin protecting against the development of cholangiocarcinoma. The work is progressing to identify further subjects to more precisely define the effect size. Aetiological work in other populations is required to determine if the association with aspirin is consistent although its use should currently be measured in aetiological studies of cholangiocarcinoma. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"surgical combined treatment patients klatzkin tumor surgery preferential method treatment patients cholangiocarcinoma associated high complications mortality levels demonstrating poor long term outcomes optimization preoperative management improvement results surgical treatment patients proximal extrahepatic bile duct carcinoma january 1998 december 2013 surgical treatment performed 36 patients 19 males 17 females klatzkin tumor 10 patients obtained postoperative chemotherapy bismuth corlette type iii iv tumor stage determined 30 83 3 patients portal vein resection performed 13 36 1 patients 27 75 5 patients underwent r0 resection postoperative mortality rate consisted 16 7 complications revealed 87 1 cases 6 16 7 patients required additional surgery interventional procedures performed 20 55 5 patients fix postoperative complications overall 5 year survival rate r0 resection group 40 1 median 29 months postoperative chemotherapy group overall 3 year survival rate 66 7 twice higher surgery group difference statistically significant p 0 35 improvement short term outcomes surgical treatment patients klatzkin tumor requires optimization preoperative management detailed adherence surgical techniques combination surgery postoperative chemotherapy showed trend improvement overall survival pubmed","probabilities":0.9799733,"Title":"Surgical and combined treatment of patients with Klatzkin's tumor","Abstract":"Surgery as being a preferential method of treatment of patients with cholangiocarcinoma is associated with high complications and mortality levels while demonstrating poor long-term outcomes. Optimization of preoperative management and improvement of the results of surgical treatment for patients with proximal extrahepatic bile duct carcinoma. From January 1998 to December 2013 surgical treatment was performed in 36 patients (19 males, 17 females) with Klatzkin's tumor, from whom 10 patients obtained postoperative chemotherapy. Bismuth-Corlette type III-IV tumor stage was determined in 30 (83.3%) patients. Portal vein resection was performed in 13 (36.1%) patients. 27 (75.5%) patients underwent R0 resection. Postoperative mortality rate consisted 16.7%, complications were revealed in 87.1% of cases. 6 (16.7%) patients required additional surgery and interventional procedures were performed in other 20 (55.5%) patients to fix postoperative complications. Overall 5-year survival rate in R0-resection group was 40.1%, median - 29 months. In postoperative chemotherapy group overall 3-year survival rate was 66.7% which was twice higher than in surgery group but the difference was not statistically significant (p=0.35). The improvement of short-term outcomes of surgical treatment for patients with Klatzkin's tumor requires optimization of preoperative management and detailed adherence of surgical techniques. Combination of surgery with postoperative chemotherapy showed the trend to improvement of overall survival.","Source":"PubMed","category":"HUMAN","training_data":"Surgical and combined treatment of patients with Klatzkin's tumor Surgery as being a preferential method of treatment of patients with cholangiocarcinoma is associated with high complications and mortality levels while demonstrating poor long-term outcomes. Optimization of preoperative management and improvement of the results of surgical treatment for patients with proximal extrahepatic bile duct carcinoma. From January 1998 to December 2013 surgical treatment was performed in 36 patients (19 males, 17 females) with Klatzkin's tumor, from whom 10 patients obtained postoperative chemotherapy. Bismuth-Corlette type III-IV tumor stage was determined in 30 (83.3%) patients. Portal vein resection was performed in 13 (36.1%) patients. 27 (75.5%) patients underwent R0 resection. Postoperative mortality rate consisted 16.7%, complications were revealed in 87.1% of cases. 6 (16.7%) patients required additional surgery and interventional procedures were performed in other 20 (55.5%) patients to fix postoperative complications. Overall 5-year survival rate in R0-resection group was 40.1%, median - 29 months. In postoperative chemotherapy group overall 3-year survival rate was 66.7% which was twice higher than in surgery group but the difference was not statistically significant (p=0.35). The improvement of short-term outcomes of surgical treatment for patients with Klatzkin's tumor requires optimization of preoperative management and detailed adherence of surgical techniques. Combination of surgery with postoperative chemotherapy showed the trend to improvement of overall survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role hepatitis viruses cholangiocarcinoma cholangiocarcinoma second common liver cancer world aetiology disease diverse incorporating variety conditions leading biliary stasis biliary liver inflammation large number cases still occur absence established risk factors incidence mortality increasing intensified search alternative aetiological agents pathogenetic mechanisms chronic infection hepatitis b hepatitis c viruses primary risk factor hepatocellular cancer review focuses epidemiological evidence role viruses cholangiocarcinoma pathogenetic mechanisms might involved pubmed","probabilities":0.9799733,"Title":"The role of the hepatitis viruses in cholangiocarcinoma","Abstract":"Cholangiocarcinoma is the second most common liver cancer in the world. The aetiology of the disease is diverse incorporating a variety of conditions leading to biliary stasis, biliary and liver inflammation, but a large number of cases still occur in the absence of established risk factors. Its incidence and mortality is increasing, which has intensified the search for alternative aetiological agents and pathogenetic mechanisms. Chronic infection with hepatitis B and hepatitis C viruses are the primary risk factor for hepatocellular cancer. This review focuses on the epidemiological evidence of a role for these viruses in cholangiocarcinoma and the pathogenetic mechanisms that might be involved.","Source":"PubMed","category":"HUMAN","training_data":"The role of the hepatitis viruses in cholangiocarcinoma Cholangiocarcinoma is the second most common liver cancer in the world. The aetiology of the disease is diverse incorporating a variety of conditions leading to biliary stasis, biliary and liver inflammation, but a large number of cases still occur in the absence of established risk factors. Its incidence and mortality is increasing, which has intensified the search for alternative aetiological agents and pathogenetic mechanisms. Chronic infection with hepatitis B and hepatitis C viruses are the primary risk factor for hepatocellular cancer. This review focuses on the epidemiological evidence of a role for these viruses in cholangiocarcinoma and the pathogenetic mechanisms that might be involved. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prediction overall survival 2nd line l2os chemotherapy ct patients advanced biliary tract cancer abtc ageo ct2bil cohort update international multicenter external validations background benefit second line chemotherapy l2 standard first line l1 gemcitabine plus cisplatin gemcis oxaliplatin gemox chemotherapy advanced biliary tract cancer abtc unclear aim identify validate prognostic factors overall survival os l2 abtc guide clinical decisions setting methods performed retrospective analysis four prospective patient cohorts development cohort 28 french centres three validation cohorts italy uk france consecutive patients abtc receiving l2 gemcis gemox l1 2003 2016 included association clinicobiological data os investigated univariate multivariate cox analyses simple score derived multivariate model results development cohort included 405 patients treated l1 gemox 91 gemcis 55 3 men median age 64 8 years prior surgical resection observed 26 7 94 8 metastatic disease performance status ps 0 1 2 17 8 52 4 29 7 respectively among 22 clinical parameters eight associated os univariate analysis multivariate analysis four independent prognostic factors p 0 05 ps reason l1 discontinuation prior resection primary tumour peritoneal carcinomatosis model harrell concordance index 0 655 good calibration validated three external cohorts n 392 conclusion validated previously reported predictive factors os l2 identified peritoneal carcinomatosis new pejorative factor nearly 800 patients model score may useful daily practice future clinical trial design stn","probabilities":0.9799733,"Title":"Prediction Of Overall Survival With 2Nd-Line (L2Os) Chemotherapy (Ct) In Patients With Advanced Biliary Tract Cancer (Abtc): Ageo Ct2Bil Cohort Update And International Multicenter External Validations","Abstract":"Background: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. \r\n\r\n Methods: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. \r\n\r\n Results: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). \r\n\r\n Conclusion: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design.","Source":"STN","category":"HUMAN","training_data":"Prediction Of Overall Survival With 2Nd-Line (L2Os) Chemotherapy (Ct) In Patients With Advanced Biliary Tract Cancer (Abtc): Ageo Ct2Bil Cohort Update And International Multicenter External Validations Background: The benefit of second-line chemotherapy (L2) over standard first-line (L1) gemcitabine plus cisplatin (GEMCIS) or oxaliplatin (GEMOX) chemotherapy in advanced biliary tract cancer (aBTC) is unclear. Our aim was to identify and validate prognostic factors for overall survival (OS) with L2 in aBTC to guide clinical decisions in this setting. \r\n\r\n Methods: We performed a retrospective analysis of four prospective patient cohorts: a development cohort (28 French centres) and three validation cohorts from Italy, UK and France. All consecutive patients with aBTC receiving L2 after GEMCIS/GEMOX L1 between 2003 and 2016 were included. The association of clinicobiological data with OS was investigated in univariate and multivariate Cox analyses. A simple score was derived from the multivariate model. \r\n\r\n Results: The development cohort included 405 patients treated with L1 GEMOX (91%) or GEMCIS. Of them, 55.3% were men, and median age was 64.8 years. Prior surgical resection was observed in 26.7%, and 94.8% had metastatic disease. Performance status (PS) was 0, 1 and 2 in 17.8%, 52.4% and 29.7%, respectively. Among 22 clinical parameters, eight were associated with OS in univariate analysis. In multivariate analysis, four were independent prognostic factors (p < 0.05): PS, reason for L1 discontinuation, prior resection of primary tumour and peritoneal carcinomatosis. The model had the Harrell's concordance index of 0.655, a good calibration and was validated in the three external cohorts (N = 392). \r\n\r\n Conclusion: We validated previously reported predictive factors of OS with L2 and identified peritoneal carcinomatosis as a new pejorative factor in nearly 800 patients. Our model and score may be useful in daily practice and for future clinical trial design. STN","prediction_labels":"HUMAN"},{"cleaned":"preoperative serum ca19 9 levels independent prognostic factor patients resected hilar cholangiocarcinoma investigate appropriate cutoff point ca19 9 prognosis potential prognostic factors may affect survival patients hilar cholangiocarcinoma hc radical surgery 168 patients undergone radical surgery hilar cholangiocarcinoma resultant macroscopic curative resection r0 r1 discreetly selected analyses categorized versions used univariate model determine appropriate cutoff point ca19 9 ca19 9 clinicopathologic factors analyzed influence survival univariate multivariate methods strongest univariate predictor among categorized preoperative ca19 9 measures ca19 9 less 150 iu l p 0 000 univariate analysis tumor size bismuth corlette classification portal vein invasion lymph node metastasis resection margin preoperative ca19 9 levels identified significant prognostic factors multivariable analysis lymph node metastasis resection margin preoperative ca19 9 levels independent prognostic factors results demonstrated preoperative ca19 9 levels also independent prognostic factor hilar cholangiocarcinoma discriminative cutoff point ca19 9 prognosis proved 150 u ml stn","probabilities":0.9799733,"Title":"Preoperative Serum Ca19-9 Levels Is An Independent Prognostic Factor In Patients With Resected Hilar Cholangiocarcinoma","Abstract":"To investigate the appropriate cutoff point of CA19-9 for prognosis and other potential prognostic factors that may affect survival of patients with hilar cholangiocarcinoma (HC) after radical surgery. 168 patients who had undergone radical surgery for hilar cholangiocarcinoma and resultant macroscopic curative resection (R0 and R1) were discreetly selected for analyses. Categorized versions were used in univariate model to determine the appropriate cutoff point of CA19-9. CA19-9 and other clinicopathologic factors were analyzed for influence on survival by univariate and multivariate methods. The strongest univariate predictor among the categorized preoperative CA19-9 measures was CA19-9 less than 150 IU/L (P = 0.000). In univariate analysis, tumor size, Bismuth-Corlette classification, portal vein invasion, Lymph node metastasis, resection margin and preoperative CA19-9 levels were identified as significant prognostic factors. In multivariable analysis, lymph node metastasis, resection margin and preoperative CA19-9 levels were independent prognostic factors. our results demonstrated that preoperative CA19-9 levels was also an independent prognostic factor for hilar cholangiocarcinoma, and the most discriminative cutoff point of CA19-9 for prognosis proved to be at 150 U/ml.","Source":"STN","category":"HUMAN","training_data":"Preoperative Serum Ca19-9 Levels Is An Independent Prognostic Factor In Patients With Resected Hilar Cholangiocarcinoma To investigate the appropriate cutoff point of CA19-9 for prognosis and other potential prognostic factors that may affect survival of patients with hilar cholangiocarcinoma (HC) after radical surgery. 168 patients who had undergone radical surgery for hilar cholangiocarcinoma and resultant macroscopic curative resection (R0 and R1) were discreetly selected for analyses. Categorized versions were used in univariate model to determine the appropriate cutoff point of CA19-9. CA19-9 and other clinicopathologic factors were analyzed for influence on survival by univariate and multivariate methods. The strongest univariate predictor among the categorized preoperative CA19-9 measures was CA19-9 less than 150 IU/L (P = 0.000). In univariate analysis, tumor size, Bismuth-Corlette classification, portal vein invasion, Lymph node metastasis, resection margin and preoperative CA19-9 levels were identified as significant prognostic factors. In multivariable analysis, lymph node metastasis, resection margin and preoperative CA19-9 levels were independent prognostic factors. our results demonstrated that preoperative CA19-9 levels was also an independent prognostic factor for hilar cholangiocarcinoma, and the most discriminative cutoff point of CA19-9 for prognosis proved to be at 150 U/ml. STN","prediction_labels":"HUMAN"},{"cleaned":"pt1b t2 incidental gallbladder carcinoma laparoscopic cholecystectomy single institute experience abstract available google scholar","probabilities":0.9799733,"Title":"Pt1B/T2 Incidental Gallbladder Carcinoma After Laparoscopic Cholecystectomy-Single Institute Experience","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Pt1B/T2 Incidental Gallbladder Carcinoma After Laparoscopic Cholecystectomy-Single Institute Experience Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"expression prognostic significance ki 67 p53 ampullary carcinoma understanding proliferative apoptotic changes aided improvement diagnosis treatment prevention gastric cancer present study aimed investigate clinicopathological prognostic significance ki 67 caspase 3 p53 gastric cancer expression levels ki 67 caspase 3 p53 evaluated tissue microarrays gastric carcinomas specimens immunohistochemistry compared clinicopathological parameters survival time patients observed elder male patients gastric cancer showed p53 overexpression compared younger female patients respectively p 0 05 expression ki 67 p53 positively associated tumor node metastasis tnm staging p 0 05 higher caspase 3 p53 expression intestinal type compared diffuse type carcinomas p 0 05 positive correlation among ki 67 caspase 3 p53 expression gastric cancer p 0 05 kaplan meier analysis indicated positive correlation caspase 3 expression adverse prognosis patients p 0 05 cox proportional hazards model indicated patient age gender depth invasion lymphatic invasion lymph node metastasis tnm staging lauren classification caspase 3 expression independent prognostic factors gastric carcinomas p 0 05 data indicated expression ki 67 caspase 3 p53 may involved progression differentiation gastric carcinoma expression may employed indicator pathobiological behavior prognosis gastric carcinomas stn","probabilities":0.7966102,"Title":"Expression And Prognostic Significance Of Ki-67 And P53 In Ampullary Carcinoma","Abstract":"The understanding of proliferative and apoptotic changes has aided the improvement of the diagnosis, treatment and prevention of gastric cancer. The present study aimed to investigate the clinicopathological and prognostic significance of Ki-67, caspase-3 and p53 in gastric cancer. The expression levels of Ki-67, caspase-3 and p53 were evaluated on tissue microarrays of gastric carcinomas specimens by immunohistochemistry and compared with the clinicopathological parameters and survival time of the patients. It was observed that the elder or male patients with gastric cancer showed p53 overexpression compared with the younger or female patients, respectively (P<0.05). The expression of Ki-67 and p53 was positively associated with tumor-node-metastasis (TNM) staging (P<0.05). There was higher caspase-3 and p53 expression in the intestinal-type compared with the diffuse-type of carcinomas (P<0.05). There was a positive correlation among Ki-67, caspase-3 and p53 expression in gastric cancer (P<0.05). A Kaplan-Meier analysis indicated that there was positive correlation between caspase-3 expression and the adverse prognosis of the patients (P>0.05). Cox's proportional hazards model indicated that the patient age, gender, depth of invasion, lymphatic invasion, lymph node metastasis, TNM staging, Lauren's classification and caspase-3 expression were independent prognostic factors for gastric carcinomas (P<0.05). The data indicated that the expression of Ki-67, caspase-3 and p53 may be involved in the progression or differentiation of gastric carcinoma. This expression may be employed as an indicator of the pathobiological behavior and prognosis of gastric carcinomas.","Source":"STN","category":"ANIMAL","training_data":"Expression And Prognostic Significance Of Ki-67 And P53 In Ampullary Carcinoma The understanding of proliferative and apoptotic changes has aided the improvement of the diagnosis, treatment and prevention of gastric cancer. The present study aimed to investigate the clinicopathological and prognostic significance of Ki-67, caspase-3 and p53 in gastric cancer. The expression levels of Ki-67, caspase-3 and p53 were evaluated on tissue microarrays of gastric carcinomas specimens by immunohistochemistry and compared with the clinicopathological parameters and survival time of the patients. It was observed that the elder or male patients with gastric cancer showed p53 overexpression compared with the younger or female patients, respectively (P<0.05). The expression of Ki-67 and p53 was positively associated with tumor-node-metastasis (TNM) staging (P<0.05). There was higher caspase-3 and p53 expression in the intestinal-type compared with the diffuse-type of carcinomas (P<0.05). There was a positive correlation among Ki-67, caspase-3 and p53 expression in gastric cancer (P<0.05). A Kaplan-Meier analysis indicated that there was positive correlation between caspase-3 expression and the adverse prognosis of the patients (P>0.05). Cox's proportional hazards model indicated that the patient age, gender, depth of invasion, lymphatic invasion, lymph node metastasis, TNM staging, Lauren's classification and caspase-3 expression were independent prognostic factors for gastric carcinomas (P<0.05). The data indicated that the expression of Ki-67, caspase-3 and p53 may be involved in the progression or differentiation of gastric carcinoma. This expression may be employed as an indicator of the pathobiological behavior and prognosis of gastric carcinomas. STN","prediction_labels":"HUMAN"},{"cleaned":"liver transplantation locally advanced intrahepatic cholangiocarcinoma treated neoadjuvant therapy prospective case series background present intrahepatic cholangiocarcinoma contraindication liver transplantation however previous studies field preselect patients basis chemosensitivity disease trajectory neoadjuvant therapy experience hilar cholangiocarcinoma indicated neoadjuvant therapy followed liver transplantation patients without disease progression results long term survival benefit aimed establish potential efficacy liver transplantation patients biologically responsive intrahepatic cholangiocarcinoma sustained tumour stability regression neoadjuvant therapy methods prospective case series patients locally advanced unresectable intrahepatic cholangiocarcinoma without extrahepatic disease vascular involvement treated single liver transplant centre according non randomised centre approved clinical management protocol neoadjuvant chemotherapy followed liver transplantation neoadjuvant therapy consisted gemcitabine based chemotherapy gemcitabine cisplatin gemcitabine capecitabine second line third line therapies given per institutional standards patients minimum 6 months radiographic response stability listed liver transplantation primary endpoints overall survival recurrence free survival liver transplantation assessed kaplan meier analysis report includes interim data initial case series treated ongoing clinical management protocol censored dec 1 2017 findings jan 1 2010 dec 1 2017 21 patients referred evaluation 12 patients accepted six patients undergone liver transplantation intrahepatic cholangiocarcinoma three patients received livers extended criteria deceased donors otherwise discarded two domino living donors one standard criteria liver donor median duration diagnosis transplantation 26 months iqr 17 33 median follow transplantation 36 months 29 51 patients received neoadjuvant chemotherapy awaiting liver transplantation overall survival 100 95 ci 100 100 1 year 83 3 27 3 97 5 3 years 83 3 27 3 97 5 5 years three patients developed recurrent disease median 7 6 months iqr 5 8 8 6 transplantation 50 95 ci 11 1 80 4 recurrence free survival 1 3 5 years adverse events liver transplantation included one patient postoperative ileus grade 3 one patient acute kidney injury requiring temporary dialysis grade 4 interpretation selected patients locally advanced intrahepatic cholangiocarcinoma show pre transplant disease stability neoadjuvant therapy might benefit liver transplantation funding none pubmed","probabilities":0.9799733,"Title":"Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series","Abstract":"BACKGROUND: At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy. METHODS: In this prospective case-series, patients with locally advanced, unresectable intrahepatic cholangiocarcinoma, without extrahepatic disease or vascular involvement, were treated at a single liver transplant centre according to a non-randomised, centre-approved clinical management protocol with neoadjuvant chemotherapy followed by liver transplantation. Neoadjuvant therapy consisted of gemcitabine-based chemotherapy, such as gemcitabine-cisplatin or gemcitabine-capecitabine, with second-line or third-line therapies given per institutional standards. Patients with a minimum of 6 months of radiographic response or stability were listed for liver transplantation. The primary endpoints were overall survival and recurrence-free survival after liver transplantation, assessed with Kaplan-Meier analysis. This report includes interim data from the initial case-series treated under this ongoing clinical management protocol, censored on Dec 1, 2017. FINDINGS: Between Jan 1, 2010, and Dec 1, 2017, 21 patients were referred for evaluation and 12 patients were accepted, of whom six patients have undergone liver transplantation for intrahepatic cholangiocarcinoma. Three patients received livers from extended criteria deceased donors that would otherwise have been discarded, two from domino living donors, and one from a standard criteria liver donor. Median duration from diagnosis to transplantation was 26 months (IQR 17-33) and median follow-up from transplantation was 36 months (29-51). All patients received neoadjuvant chemotherapy while awaiting liver transplantation. Overall survival was 100% (95% CI 100-100) at 1 year, 83·3% (27·3-97·5) at 3 years, and 83·3% (27·3-97·5) at 5 years. Three patients developed recurrent disease at a median of 7·6 months (IQR 5·8-8·6) after transplantation, with 50% (95% CI 11·1-80·4) recurrence-free survival at 1, 3, and 5 years. Adverse events after liver transplantation included one patient with postoperative ileus (grade 3) and one patient with acute kidney injury requiring temporary dialysis (grade 4). INTERPRETATION: Selected patients with locally advanced intrahepatic cholangiocarcinoma who show pre-transplant disease stability on neoadjuvant therapy might benefit from liver transplantation. FUNDING: None.","Source":"PubMed","category":"HUMAN","training_data":"Liver transplantation for locally advanced intrahepatic cholangiocarcinoma treated with neoadjuvant therapy: a prospective case-series BACKGROUND: At present, intrahepatic cholangiocarcinoma is a contraindication for liver transplantation. However, previous studies in this field did not preselect patients on the basis of chemosensitivity or disease trajectory after neoadjuvant therapy. Experience with hilar cholangiocarcinoma has indicated that neoadjuvant therapy followed by liver transplantation in patients without disease progression results in a long-term survival benefit. We aimed to establish the potential efficacy of liver transplantation in patients with biologically responsive intrahepatic cholangiocarcinoma who have had sustained tumour stability or regression with neoadjuvant therapy. METHODS: In this prospective case-series, patients with locally advanced, unresectable intrahepatic cholangiocarcinoma, without extrahepatic disease or vascular involvement, were treated at a single liver transplant centre according to a non-randomised, centre-approved clinical management protocol with neoadjuvant chemotherapy followed by liver transplantation. Neoadjuvant therapy consisted of gemcitabine-based chemotherapy, such as gemcitabine-cisplatin or gemcitabine-capecitabine, with second-line or third-line therapies given per institutional standards. Patients with a minimum of 6 months of radiographic response or stability were listed for liver transplantation. The primary endpoints were overall survival and recurrence-free survival after liver transplantation, assessed with Kaplan-Meier analysis. This report includes interim data from the initial case-series treated under this ongoing clinical management protocol, censored on Dec 1, 2017. FINDINGS: Between Jan 1, 2010, and Dec 1, 2017, 21 patients were referred for evaluation and 12 patients were accepted, of whom six patients have undergone liver transplantation for intrahepatic cholangiocarcinoma. Three patients received livers from extended criteria deceased donors that would otherwise have been discarded, two from domino living donors, and one from a standard criteria liver donor. Median duration from diagnosis to transplantation was 26 months (IQR 17-33) and median follow-up from transplantation was 36 months (29-51). All patients received neoadjuvant chemotherapy while awaiting liver transplantation. Overall survival was 100% (95% CI 100-100) at 1 year, 83·3% (27·3-97·5) at 3 years, and 83·3% (27·3-97·5) at 5 years. Three patients developed recurrent disease at a median of 7·6 months (IQR 5·8-8·6) after transplantation, with 50% (95% CI 11·1-80·4) recurrence-free survival at 1, 3, and 5 years. Adverse events after liver transplantation included one patient with postoperative ileus (grade 3) and one patient with acute kidney injury requiring temporary dialysis (grade 4). INTERPRETATION: Selected patients with locally advanced intrahepatic cholangiocarcinoma who show pre-transplant disease stability on neoadjuvant therapy might benefit from liver transplantation. FUNDING: None. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pathologic t1 subclassification ampullary carcinoma perisphincteric duodenal submucosal invasion t1b context ampullary carcinoma staging t1 defined tumor limited ampulla vater sphincter oddi t2 defined invasion duodenal wall however definition duodenal wall invasion vague ampullary carcinoma invades beyond sphincteric oddi perisphincteric invasion duodenal submucosa considered pt1b submucosal invasion classified pt1b gastrointestinal tract tumors however data regarding subclassifications ampullary carcinoma perisphincteric duodenal submucosa invasion objective determine subclassification ampullary carcinoma invades perisphincteric duodenal submucosa design pathologically proven ampullary carcinomas t1 t2 reviewed n 105 reclassified tumors pt1a limited within sphincter oddi n 40 38 pt1b tumors invaded beyond sphincter oddi duodenal submucosa n 25 24 pt2 tumors invaded duodenal proper muscle n 40 38 results lymph node metastasis recurrence absent ampullary carcinoma pt1a whereas nodal metastasis noted 24 6 25 40 16 40 ampullary carcinomas pt1b pt2 respectively tumor recurrence metastasis rate ampullary carcinoma pt1b pt2 44 11 25 40 16 40 respectively 5 year disease free survival rates ampullary carcinoma pt1a pt1b pt2 95 38 40 56 14 25 58 23 40 respectively p 003 5 year overall survival ampullary carcinoma pt1a pt1b pt2 98 39 40 72 18 25 60 24 40 respectively conclusions clinicopathologic outcome ampullary carcinoma pt1b subclassification worse t1a approached outcome pt2 pubmed","probabilities":0.9799733,"Title":"Pathologic T1 subclassification of ampullary carcinoma with perisphincteric or duodenal submucosal invasion: Is it T1b?","Abstract":"CONTEXT: In ampullary carcinoma staging, T1 is defined as a tumor limited to the ampulla of Vater or the sphincter of Oddi, and T2 is defined as invasion into the duodenal wall. However, the definition of duodenal wall invasion is vague. Ampullary carcinoma that invades beyond the sphincteric of Oddi (perisphincteric invasion) or into the duodenal submucosa could be considered pT1b because submucosal invasion is classified as pT1b in gastrointestinal tract tumors. However, there are no data regarding T subclassifications for ampullary carcinoma with perisphincteric or duodenal submucosa invasion. OBJECTIVE: To determine the T subclassification of ampullary carcinoma that invades into perisphincteric or duodenal submucosa. DESIGN: Pathologically proven ampullary carcinomas with T1 or T2 were reviewed (n = 105). We reclassified tumors as pT1a that were limited to within the sphincter of Oddi (n = 40; 38%), as pT1b for tumors that invaded beyond the sphincter of Oddi or into the duodenal submucosa (n = 25; 24%), and as pT2 for tumors that invaded into duodenal proper muscle (n = 40; 38%). RESULTS: Lymph node metastasis and recurrence were absent in ampullary carcinoma with pT1a, whereas nodal metastasis were noted in 24% (6 of 25) and 40% (16 of 40) of the ampullary carcinomas with pT1b and pT2, respectively. Tumor recurrence/metastasis rate of ampullary carcinoma with pT1b and pT2 was 44% (11 of 25) and 40% (16 of 40), respectively. The 5-year disease-free-survival rates from ampullary carcinoma with pT1a, pT1b, and pT2 were 95% (38 of 40), 56% (14 of 25), and 58% (23 of 40), respectively (P = .003). The 5-year overall survival from ampullary carcinoma with pT1a, pT1b, and pT2 was 98% (39 of 40), 72% (18 of 25), and 60% (24 of 40), respectively. CONCLUSIONS: The clinicopathologic outcome of ampullary carcinoma with a pT1b subclassification was worse than it was for T1a and approached the outcome for pT2.","Source":"PubMed","category":"HUMAN","training_data":"Pathologic T1 subclassification of ampullary carcinoma with perisphincteric or duodenal submucosal invasion: Is it T1b? CONTEXT: In ampullary carcinoma staging, T1 is defined as a tumor limited to the ampulla of Vater or the sphincter of Oddi, and T2 is defined as invasion into the duodenal wall. However, the definition of duodenal wall invasion is vague. Ampullary carcinoma that invades beyond the sphincteric of Oddi (perisphincteric invasion) or into the duodenal submucosa could be considered pT1b because submucosal invasion is classified as pT1b in gastrointestinal tract tumors. However, there are no data regarding T subclassifications for ampullary carcinoma with perisphincteric or duodenal submucosa invasion. OBJECTIVE: To determine the T subclassification of ampullary carcinoma that invades into perisphincteric or duodenal submucosa. DESIGN: Pathologically proven ampullary carcinomas with T1 or T2 were reviewed (n = 105). We reclassified tumors as pT1a that were limited to within the sphincter of Oddi (n = 40; 38%), as pT1b for tumors that invaded beyond the sphincter of Oddi or into the duodenal submucosa (n = 25; 24%), and as pT2 for tumors that invaded into duodenal proper muscle (n = 40; 38%). RESULTS: Lymph node metastasis and recurrence were absent in ampullary carcinoma with pT1a, whereas nodal metastasis were noted in 24% (6 of 25) and 40% (16 of 40) of the ampullary carcinomas with pT1b and pT2, respectively. Tumor recurrence/metastasis rate of ampullary carcinoma with pT1b and pT2 was 44% (11 of 25) and 40% (16 of 40), respectively. The 5-year disease-free-survival rates from ampullary carcinoma with pT1a, pT1b, and pT2 were 95% (38 of 40), 56% (14 of 25), and 58% (23 of 40), respectively (P = .003). The 5-year overall survival from ampullary carcinoma with pT1a, pT1b, and pT2 was 98% (39 of 40), 72% (18 of 25), and 60% (24 of 40), respectively. CONCLUSIONS: The clinicopathologic outcome of ampullary carcinoma with a pT1b subclassification was worse than it was for T1a and approached the outcome for pT2. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment survival resected unresected distal cholangiocarcinoma nationwide study background population based data distal cholangiocarcinoma dcc western world available albeit essential identify areas improvement study investigated incidence treatment outcomes including time trends predictors survival nationwide cohort dcc methods retrospective cohort study patients diagnosed dcc 2009 2016 derived netherlands cancer registry overall survival os predictors analyzed using kaplan meier cox regression analysis time trends 2009 2012 versus 2013 2016 assessed results overall 1338 patients dcc included 1 3 5 year os 46 18 11 incidence dcc 0 55 0 90 per 100 000 per year median os 10 4 months across stages 21 9 months resected n 620 46 3 6 7 months unresected nonmetastatic n 445 33 3 3 6 months metastatic dcc n 273 20 4 p 001 resection 30 day mortality 4 8 90 day mortality 7 7 patients metastatic dcc received chemotherapy n 78 28 6 median os 8 2 versus 2 8 months treated p 001 time resection rates 53 6 61 7 p 008 use palliative chemotherapy metastatic dcc 22 3 32 9 p 05 increased without improvement os 10 3 vs 10 6 months p 55 independent poor prognostic factors os resected disease increasing age pt3 t4 stage higher lymph node ratio poor differentiation r1 resection conclusions nationwide cohort dcc resection rates use chemotherapy increased whereas os remained stable 10 4 months pubmed","probabilities":0.9799733,"Title":"Treatment and survival of resected and unresected distal cholangiocarcinoma: a nationwide study","Abstract":"Background: Population-based data on distal cholangiocarcinoma (DCC) from the Western world are not available, albeit essential to identify areas for improvement. This study investigated the incidence, treatment and outcomes, including time trends and predictors for survival, in a nationwide cohort of DCC. Methods: This is a retrospective cohort study of patients diagnosed with DCC (2009-2016) derived from the Netherlands Cancer Registry. Overall survival (OS) and its predictors were analyzed using Kaplan-Meier and Cox regression analysis. Time trends (2009-2012 versus 2013-2016) were assessed. Results: Overall, 1338 patients with DCC were included, with 1-, 3- and 5-year OS of 46%, 18%, and 11%. Incidence of DCC was 0.55-0.90 per 100.000 per year. Median OS was 10.4 months across all stages; 21.9 months for resected (n = 620, 46.3%), 6.7 months for unresected nonmetastatic (n = 445, 33.3%), and 3.6 months for metastatic DCC (n = 273, 20.4%) (p < .001). After resection, 30-day mortality was 4.8% and 90-day mortality 7.7%. Patients with metastatic DCC who received chemotherapy (n = 78, 28.6%) had a median OS of 8.2 versus 2.8 months for those not treated (p < .001). Over time, resection rates (53.6% to 61.7%, p = .008) and use of palliative chemotherapy in metastatic DCC (22.3% to 32.9%, p = .05) increased, without improvement in OS (10.3 vs 10.6 months, p = .55). Independent poor prognostic factors for OS in resected disease were increasing age, pT3/T4 stage, higher lymph node ratio, poor differentiation, and R1 resection. Conclusions: In a nationwide cohort of DCC, resection rates and the use of chemotherapy increased whereas OS remained stable at 10.4 months.","Source":"PubMed","category":"HUMAN","training_data":"Treatment and survival of resected and unresected distal cholangiocarcinoma: a nationwide study Background: Population-based data on distal cholangiocarcinoma (DCC) from the Western world are not available, albeit essential to identify areas for improvement. This study investigated the incidence, treatment and outcomes, including time trends and predictors for survival, in a nationwide cohort of DCC. Methods: This is a retrospective cohort study of patients diagnosed with DCC (2009-2016) derived from the Netherlands Cancer Registry. Overall survival (OS) and its predictors were analyzed using Kaplan-Meier and Cox regression analysis. Time trends (2009-2012 versus 2013-2016) were assessed. Results: Overall, 1338 patients with DCC were included, with 1-, 3- and 5-year OS of 46%, 18%, and 11%. Incidence of DCC was 0.55-0.90 per 100.000 per year. Median OS was 10.4 months across all stages; 21.9 months for resected (n = 620, 46.3%), 6.7 months for unresected nonmetastatic (n = 445, 33.3%), and 3.6 months for metastatic DCC (n = 273, 20.4%) (p < .001). After resection, 30-day mortality was 4.8% and 90-day mortality 7.7%. Patients with metastatic DCC who received chemotherapy (n = 78, 28.6%) had a median OS of 8.2 versus 2.8 months for those not treated (p < .001). Over time, resection rates (53.6% to 61.7%, p = .008) and use of palliative chemotherapy in metastatic DCC (22.3% to 32.9%, p = .05) increased, without improvement in OS (10.3 vs 10.6 months, p = .55). Independent poor prognostic factors for OS in resected disease were increasing age, pT3/T4 stage, higher lymph node ratio, poor differentiation, and R1 resection. Conclusions: In a nationwide cohort of DCC, resection rates and the use of chemotherapy increased whereas OS remained stable at 10.4 months. PubMed","prediction_labels":"HUMAN"},{"cleaned":"temporal trends incidence intra extrahepatic cholangiocarcinoma united states impact klatskin tumor classification background aims previous studies cholangiocarcinoma reported increasing incidence intrahepatic icc decreasing incidence extrahepatic ecc united states hilar cholangiocarcinomas klatskin tumors anatomically defined ecc affected trends version 1 international classification diseases oncology icd o 1973 1991 klatskin tumors assigned unique icd o code may coded either icc ecc icd o version 2 19922000 assigned unique histology code 8162 3 cross referenced icc icd o version 3 2000 present cross referenced klatskin tumors either icc ecc thus klatskin tumors may misclassified icc versions icdo conducted study determine 1 secular trends icc ecc 19922007 2 potential impact misclassification bias trends methods using data surveillance epidemiology end results seer program age adjusted incidence rates icc ecc calculated two consecutive time periods 19922000 2001 2007 following definitions used icc topography codes c22 0 liver c22 1 intra hepatic bile duct histology codes 8140 8160 8161 8020 8010 ecc topography code c24 0 histology codes 8010 8020 8041 8070 8140 8144 8160 8161 8260 8310 8480 8490 8560 klatskin histology code 8162 3 calculated annual percent change apc incidence rates utilizing weighted least squares method results identified 4297 patients icc 2679 patients ecc 1992 2007 age adjusted rates per 100 000 icc excluding klatskin tumors e true icc rate decreased 1 5 1992 2000 1 4 2001 2007 apc 0 3 95 c 1 5 0 8 whereas true ecc rates including klatskin tumors significantly increased 0 8 1 1 time periods apc 3 3 95 c 2 0 4 5 increased incidence ecc pronounced males apc 3 6 95 c 2 0 5 1 asians pacific islanders apc 4 5 65 age group apc 3 9 1992 2000 208 224 93 cases klatskin tumors misclassified icc proportion dropped 60 144 42 2001 2007 however even misclassification incidence rate icc including klatskin tumors declined 1 6 1 4 per 100 000 two time periods apc 0 9 95 c 2 1 0 3 conclusions contrary recent data incidence rates icc us remained stable period 1992 2007 whereas ecc rates risen improved classification klatskin tumors may explain trends google scholar","probabilities":0.9799733,"Title":"The Temporal Trends In Incidence Of Intra And Extrahepatic Cholangiocarcinoma In The United States And The Impact Of Klatskin Tumor Classification","Abstract":"Background and Aims: Previous studies of cholangiocarcinoma have reported an increasing incidence of intrahepatic (ICC) and a decreasing incidence of extrahepatic (ECC) in the United States. Hilar cholangiocarcinomas (Klatskin tumors) are anatomically defined as ECC and could have affected these trends. In version 1 of the International Classification of Diseases for Oncology (ICD-O) (1973-1991), Klatskin tumors were not assigned a unique ICD-O code and may have been coded as either ICC or ECC. In ICD-O version 2 (19922000), they were assigned a unique histology code (8162/3) which was cross-referenced to ICC. ICD-O version 3 (2000-present) cross-referenced Klatskin tumors to either ICC or ECC. Thus, Klatskin tumors may have been misclassified as ICC under all versions of ICDO. We conducted this study to determine 1) the secular trends of ICC and ECC from 19922007 and 2) the potential impact of misclassification bias on these trends. Methods: Using data from the Surveillance, Epidemiology and End Results (SEER) program, age-adjusted incidence rates of ICC and ECC were calculated in two consecutive time periods (19922000, 2001-2007). Following definitions were used: ICC: topography codes C22.0 (Liver) and C22.1 (Intra-hepatic bile duct) and histology codes 8140, 8160, 8161, 8020, and 8010. ECC: topography code C24.0; histology codes 8010, 8020, 8041, 8070, 8140, 8144, 8160, 8161, 8260, 8310, 8480, 8490, and 8560. Klatskin: histology code 8162/3. We calculated the annual percent change (APC) in incidence rates, utilizing a weighted least squares method. Results: We identified 4297 patients with ICC and 2679 patients with ECC during 1992-2007. The age adjusted rates (per 100,000) for ICC excluding Klatskin tumors (i.e., true ICC rate) decreased from 1.5 during 1992-2000 to 1.4 in 2001-2007 with an APC of -0.3% (95% C.I.: 1.5, 0.8), whereas true ECC rates, including Klatskin tumors significantly increased from 0.8 to 1.1 during the same time periods with an APC of 3.3% (95% C.I.: 2.0, 4.5). The increased incidence of ECC was more pronounced in males (APC 3.6%, 95% C.I.: 2.0, 5.1), Asians and pacific islanders (APC 4.5%) and in the 65+ age group (APC 3.9%). During 1992-2000, 208/224 (93%) cases of Klatskin tumors were misclassified as ICC's. This proportion dropped to 60/144 (42%) in 2001-2007. However, even with misclassification the incidence rate for ICC (including Klatskin tumors) declined from 1.6 to 1.4 per 100,000 during the two time periods with an APC of -0.9% (95% C.I -2.1, 0.3). Conclusions: Contrary to recent data, the incidence rates of ICC in the US have remained stable during the period 1992-2007, whereas ECC rates have risen. Improved classification of Klatskin tumors may explain some but not all of these trends.","Source":"Google Scholar","category":"HUMAN","training_data":"The Temporal Trends In Incidence Of Intra And Extrahepatic Cholangiocarcinoma In The United States And The Impact Of Klatskin Tumor Classification Background and Aims: Previous studies of cholangiocarcinoma have reported an increasing incidence of intrahepatic (ICC) and a decreasing incidence of extrahepatic (ECC) in the United States. Hilar cholangiocarcinomas (Klatskin tumors) are anatomically defined as ECC and could have affected these trends. In version 1 of the International Classification of Diseases for Oncology (ICD-O) (1973-1991), Klatskin tumors were not assigned a unique ICD-O code and may have been coded as either ICC or ECC. In ICD-O version 2 (19922000), they were assigned a unique histology code (8162/3) which was cross-referenced to ICC. ICD-O version 3 (2000-present) cross-referenced Klatskin tumors to either ICC or ECC. Thus, Klatskin tumors may have been misclassified as ICC under all versions of ICDO. We conducted this study to determine 1) the secular trends of ICC and ECC from 19922007 and 2) the potential impact of misclassification bias on these trends. Methods: Using data from the Surveillance, Epidemiology and End Results (SEER) program, age-adjusted incidence rates of ICC and ECC were calculated in two consecutive time periods (19922000, 2001-2007). Following definitions were used: ICC: topography codes C22.0 (Liver) and C22.1 (Intra-hepatic bile duct) and histology codes 8140, 8160, 8161, 8020, and 8010. ECC: topography code C24.0; histology codes 8010, 8020, 8041, 8070, 8140, 8144, 8160, 8161, 8260, 8310, 8480, 8490, and 8560. Klatskin: histology code 8162/3. We calculated the annual percent change (APC) in incidence rates, utilizing a weighted least squares method. Results: We identified 4297 patients with ICC and 2679 patients with ECC during 1992-2007. The age adjusted rates (per 100,000) for ICC excluding Klatskin tumors (i.e., true ICC rate) decreased from 1.5 during 1992-2000 to 1.4 in 2001-2007 with an APC of -0.3% (95% C.I.: 1.5, 0.8), whereas true ECC rates, including Klatskin tumors significantly increased from 0.8 to 1.1 during the same time periods with an APC of 3.3% (95% C.I.: 2.0, 4.5). The increased incidence of ECC was more pronounced in males (APC 3.6%, 95% C.I.: 2.0, 5.1), Asians and pacific islanders (APC 4.5%) and in the 65+ age group (APC 3.9%). During 1992-2000, 208/224 (93%) cases of Klatskin tumors were misclassified as ICC's. This proportion dropped to 60/144 (42%) in 2001-2007. However, even with misclassification the incidence rate for ICC (including Klatskin tumors) declined from 1.6 to 1.4 per 100,000 during the two time periods with an APC of -0.9% (95% C.I -2.1, 0.3). Conclusions: Contrary to recent data, the incidence rates of ICC in the US have remained stable during the period 1992-2007, whereas ECC rates have risen. Improved classification of Klatskin tumors may explain some but not all of these trends. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"histone deacetylases inhibitors potential therapeutic drugs cholangiocarcinoma cell line findings histone deacetylation mediated histone deacetylases hdacs reported one epigenetic mechanisms associated tumorigenesis poor responsiveness anticancer drugs found cholangiocarcinoma cca leads short survival rate aimed investigate mrna expression hdacs class ii effect hdac inhibitors suberoylanilide hydroxamic acid saha valproic acid vpa cca vitro expression hdacs studied cca cell lines m213 m214 kku 100 immortal cholangiocyte mmnk1 semi quantitative reverse transcription pcr saha vpa well classical chemotherapeutic drug 5 fluorouracil 5 fu used study cell proliferation determined sulforhodamine assay ic50 ic20 analyzed agent cell line moreover synergistic potential vpa saha combination 5 fu subtoxic dose ic20 agent also evaluated statistic difference hdacs expression cell proliferation experimental condition analyzed student test result demonstrated hdacs expressed studied cell types saha vpa inhibited cell proliferation dose dependent manner interestingly kku 100 less sensitive classical chemotherapeutic 5 fu highly sensitive hdac inhibitors simultaneous combination subtoxic doses hdac inhibitors 5 fu significantly inhibited cell proliferation cca cell lines compared single agent treatment p 0 01 sequentially combined treatments less effective present study showed inhibitory effects hdacis cell proliferation cca cell lines synergistic antitumor potential demonstrated simultaneous combination vpa saha 5 fu suggesting novel alternative therapeutic strategy effective treatment cca stn","probabilities":0.9467213,"Title":"Histone Deacetylases And Their Inhibitors As Potential Therapeutic Drugs For Cholangiocarcinoma - Cell Line Findings","Abstract":"Histone deacetylation mediated by histone deacetylases (HDACs) has been reported as one of the epigenetic mechanisms associated with tumorigenesis. The poor responsiveness of anticancer drugs found with cholangiocarcinoma (CCA) leads to short survival rate. We aimed to investigate mRNA expression of HDACs class I and II, and the effect of HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), in CCA in vitro. Expression of HDACs was studied in CCA cell lines (M213, M214 and KKU-100) and an immortal cholangiocyte (MMNK1) by semi-quantitative reverse transcription-PCR. SAHA and VPA, as well as a classical chemotherapeutic drug 5-fluorouracil (5-FU) were used in this study. Cell proliferation was determined by sulforhodamine assay. IC50 and IC20 were then analyzed for each agent and cell line. Moreover, synergistic potential of VPA or SAHA in combination with 5-FU at subtoxic dose (IC20) of each agent was also evaluated. Statistic difference of HDACs expression or cell proliferation in each experimental condition was analyzed by Student's t-test. The result demonstrated that HDACs were expressed in all studied cell types. Both SAHA and VPA inhibited cell proliferation in a dose-dependent manner. Interestingly, KKU-100 which was less sensitive to classical chemotherapeutic 5-FU was highly sensitive to HDAC inhibitors. Simultaneous combination of subtoxic doses of HDAC inhibitors and 5-FU significantly inhibited cell proliferation in CCA cell lines compared to single agent treatment (P ≤ 0.01), while sequentially combined treatments were less effective. The present study showed inhibitory effects of HDACIs on cell proliferation in CCA cell lines, with synergistic antitumor potential demonstrated by simultaneous combination of VPA or SAHA with 5-FU, suggesting a novel alternative therapeutic strategy in effective treatment of CCA.","Source":"STN","category":"ANIMAL","training_data":"Histone Deacetylases And Their Inhibitors As Potential Therapeutic Drugs For Cholangiocarcinoma - Cell Line Findings Histone deacetylation mediated by histone deacetylases (HDACs) has been reported as one of the epigenetic mechanisms associated with tumorigenesis. The poor responsiveness of anticancer drugs found with cholangiocarcinoma (CCA) leads to short survival rate. We aimed to investigate mRNA expression of HDACs class I and II, and the effect of HDAC inhibitors, suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA), in CCA in vitro. Expression of HDACs was studied in CCA cell lines (M213, M214 and KKU-100) and an immortal cholangiocyte (MMNK1) by semi-quantitative reverse transcription-PCR. SAHA and VPA, as well as a classical chemotherapeutic drug 5-fluorouracil (5-FU) were used in this study. Cell proliferation was determined by sulforhodamine assay. IC50 and IC20 were then analyzed for each agent and cell line. Moreover, synergistic potential of VPA or SAHA in combination with 5-FU at subtoxic dose (IC20) of each agent was also evaluated. Statistic difference of HDACs expression or cell proliferation in each experimental condition was analyzed by Student's t-test. The result demonstrated that HDACs were expressed in all studied cell types. Both SAHA and VPA inhibited cell proliferation in a dose-dependent manner. Interestingly, KKU-100 which was less sensitive to classical chemotherapeutic 5-FU was highly sensitive to HDAC inhibitors. Simultaneous combination of subtoxic doses of HDAC inhibitors and 5-FU significantly inhibited cell proliferation in CCA cell lines compared to single agent treatment (P ≤ 0.01), while sequentially combined treatments were less effective. The present study showed inhibitory effects of HDACIs on cell proliferation in CCA cell lines, with synergistic antitumor potential demonstrated by simultaneous combination of VPA or SAHA with 5-FU, suggesting a novel alternative therapeutic strategy in effective treatment of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"high grade dysplasia carcinoma situ biliary duct margin affect prognosis extrahepatic cholangiocarcinoma meta analysis background high grade dysplasia carcinoma situ hgd cis biliary duct margin found affect prognosis patients extrahepatic cholangiocarcinoma recent studies yet reached conclusion methods eligible studies searched pubmed pmc medline embase cochrane library web science jan 1 2000 jun 30 2019 investigating influences surgical margin status biliary duct prognosis patients resectable extrahepatic cholangiocarcinoma overall survival os local recurrence evaluated odds ratio 95 confidence interval ci results total 11 studies enrolled meta analysis including 1734 patients r0 group 194 patients hgd cis group 229 patients invasive carcinoma inv group pooled 1 2 3 year os rate hgd cis group r0 group 0 98 95 ci 0 65 1 50 1 01 95 ci 0 73 1 41 0 98 95 ci 0 72 1 34 respectively pooled 1 2 3 year os rate hgd cis group inv group 1 83 95 ci 1 09 3 06 4 52 95 ci 2 20 9 26 3 74 95 ci 2 34 5 96 respectively subgroup analysis extrahepatic cholangiocarcinoma early stage showed pooled 1 2 3 year os rate hgd cis group r0 group 0 54 95 ci 0 21 1 36 0 75 95 ci 0 35 1 58 0 74 95 ci 0 40 1 37 respectively pooled 1 2 3 year os rate hgd cis group inv group 3 47 95 ci 1 09 11 02 9 12 95 ci 2 98 27 93 9 17 95 ci 2 95 28 55 respectively however pooled incidence local recurrence hgd cis group r0 group 3 54 95 ci 1 66 7 53 pooled incidence local recurrence hgd cis group inv group 0 93 95 ci 0 50 1 74 conclusion current data concluded hgd cis increase risk local recurrence compared r0 although affect prognosis patients extrahepatic cholangiocarcinoma regardless tnm stage however conclusion needs furtherly confirmed pubmed","probabilities":0.9799733,"Title":"Does high-grade dysplasia/carcinoma in situ of the biliary duct margin affect the prognosis of extrahepatic cholangiocarcinoma? A meta-analysis","Abstract":"BACKGROUND: High-grade dysplasia/carcinoma in situ (HGD/CIS) of the biliary duct margin was found to not affect the prognosis of patients with extrahepatic cholangiocarcinoma by recent studies, but it has not yet reached a conclusion. METHODS: Eligible studies were searched by PubMed, PMC, MedLine, Embase, the Cochrane Library, and Web of Science, from Jan. 1, 2000 to Jun. 30, 2019, investigating the influences of surgical margin status of biliary duct on the prognosis of patients with resectable extrahepatic cholangiocarcinoma. Overall survival (OS) and local recurrence were evaluated by odds ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 11 studies were enrolled in this meta-analysis, including 1734 patients in the R0 group, 194 patients in the HGD/CIS group, and 229 patients in the invasive carcinoma (INV) group. The pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and R0 group was 0.98 (95% CI 0.65~1.50), 1.01 (95% CI 0.73~1.41), and 0.98 (95% CI 0.72~1.34), respectively. The pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and INV group was 1.83 (95% CI 1.09~3.06), 4.52 (95% CI 2.20~9.26), and 3.74 (95% CI 2.34~5.96), respectively. Subgroup analysis of extrahepatic cholangiocarcinoma at early stage showed that the pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and R0 group was 0.54 (95% CI 0.21~1.36), 0.75 (95% CI 0.35~1.58), and 0.74 (95% CI 0.40~1.37), respectively, and the pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and INV group was 3.47 (95% CI 1.09~11.02), 9.12 (95% CI 2.98~27.93), and 9.17 (95% CI 2.95~28.55), respectively. However, the pooled OR for the incidence of local recurrence between HGD/CIS group and R0 group was 3.54 (95% CI 1.66~7.53), and the pooled OR for the incidence of local recurrence between HGD/CIS group and INV group was 0.93 (95% CI 0.50~1.74). CONCLUSION: With the current data, we concluded that HGD/CIS would increase the risk of local recurrence compared with R0, although it did not affect the prognosis of patients with extrahepatic cholangiocarcinoma regardless of TNM stage. However, the conclusion needs to be furtherly confirmed.","Source":"PubMed","category":"HUMAN","training_data":"Does high-grade dysplasia/carcinoma in situ of the biliary duct margin affect the prognosis of extrahepatic cholangiocarcinoma? A meta-analysis BACKGROUND: High-grade dysplasia/carcinoma in situ (HGD/CIS) of the biliary duct margin was found to not affect the prognosis of patients with extrahepatic cholangiocarcinoma by recent studies, but it has not yet reached a conclusion. METHODS: Eligible studies were searched by PubMed, PMC, MedLine, Embase, the Cochrane Library, and Web of Science, from Jan. 1, 2000 to Jun. 30, 2019, investigating the influences of surgical margin status of biliary duct on the prognosis of patients with resectable extrahepatic cholangiocarcinoma. Overall survival (OS) and local recurrence were evaluated by odds ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 11 studies were enrolled in this meta-analysis, including 1734 patients in the R0 group, 194 patients in the HGD/CIS group, and 229 patients in the invasive carcinoma (INV) group. The pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and R0 group was 0.98 (95% CI 0.65~1.50), 1.01 (95% CI 0.73~1.41), and 0.98 (95% CI 0.72~1.34), respectively. The pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and INV group was 1.83 (95% CI 1.09~3.06), 4.52 (95% CI 2.20~9.26), and 3.74 (95% CI 2.34~5.96), respectively. Subgroup analysis of extrahepatic cholangiocarcinoma at early stage showed that the pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and R0 group was 0.54 (95% CI 0.21~1.36), 0.75 (95% CI 0.35~1.58), and 0.74 (95% CI 0.40~1.37), respectively, and the pooled OR for the 1-, 2-, and 3-year OS rate between HGD/CIS group and INV group was 3.47 (95% CI 1.09~11.02), 9.12 (95% CI 2.98~27.93), and 9.17 (95% CI 2.95~28.55), respectively. However, the pooled OR for the incidence of local recurrence between HGD/CIS group and R0 group was 3.54 (95% CI 1.66~7.53), and the pooled OR for the incidence of local recurrence between HGD/CIS group and INV group was 0.93 (95% CI 0.50~1.74). CONCLUSION: With the current data, we concluded that HGD/CIS would increase the risk of local recurrence compared with R0, although it did not affect the prognosis of patients with extrahepatic cholangiocarcinoma regardless of TNM stage. However, the conclusion needs to be furtherly confirmed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"retrospective analysis survival benefits chemotherapy metastatic non resectable intrahepatic cholangiocarcinoma objective study examined effect systemic chemotherapy survival patients metastatic non resectable intrahepatic cholangiocarcinoma methods study retrospectively reviewed data 23 consecutive patients metastatic cholangiocarcinoma diagnosed treated centre 2000 2007 patients eligible intrahepatic cholangiocarcinoma liver extrahepatic metastasis prior chemotherapy univariate multivariate analyses performed determine impact age sex presence extrahepatic metastasis performance status type chemotherapy number lines chemotherapy results median survival patients 27 7 months 17 8 37 7 univariate analysis showed age less 60 years diagnosis good performance status extrahepatic liver metastasis number lines chemotherapy significantly associated better survival multivariate analysis identified performance status number lines chemotherapy independent predictive factors survival conclusion data suggest iterative chemotherapy may increase survival patients metastatic cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Retrospective analysis of survival benefits of chemotherapy for metastatic or non-resectable intrahepatic cholangiocarcinoma","Abstract":"OBJECTIVE: This study examined the effect of systemic chemotherapy on survival in patients with metastatic or non-resectable intrahepatic cholangiocarcinoma. METHODS: This study retrospectively reviewed data from 23 consecutive patients with metastatic cholangiocarcinoma diagnosed and treated in our centre between 2000 and 2007. Patients were eligible if they had intrahepatic cholangiocarcinoma with liver or extrahepatic metastasis and with no prior chemotherapy. Univariate and multivariate analyses were performed to determine the impact of age, sex, presence of extrahepatic metastasis, performance status, type of chemotherapy, number of lines of chemotherapy. RESULTS: The median survival of all patients was 27.7 months (17.8-37.7). Univariate analysis showed that age less than 60 years at diagnosis, good performance status, no extrahepatic liver metastasis and the number of lines of chemotherapy were significantly associated with better survival. Multivariate analysis identified only performance status and the number of lines of chemotherapy as independent predictive factors of survival. CONCLUSION: Our data suggest that iterative chemotherapy may increase survival in patients with metastatic cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Retrospective analysis of survival benefits of chemotherapy for metastatic or non-resectable intrahepatic cholangiocarcinoma OBJECTIVE: This study examined the effect of systemic chemotherapy on survival in patients with metastatic or non-resectable intrahepatic cholangiocarcinoma. METHODS: This study retrospectively reviewed data from 23 consecutive patients with metastatic cholangiocarcinoma diagnosed and treated in our centre between 2000 and 2007. Patients were eligible if they had intrahepatic cholangiocarcinoma with liver or extrahepatic metastasis and with no prior chemotherapy. Univariate and multivariate analyses were performed to determine the impact of age, sex, presence of extrahepatic metastasis, performance status, type of chemotherapy, number of lines of chemotherapy. RESULTS: The median survival of all patients was 27.7 months (17.8-37.7). Univariate analysis showed that age less than 60 years at diagnosis, good performance status, no extrahepatic liver metastasis and the number of lines of chemotherapy were significantly associated with better survival. Multivariate analysis identified only performance status and the number of lines of chemotherapy as independent predictive factors of survival. CONCLUSION: Our data suggest that iterative chemotherapy may increase survival in patients with metastatic cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pathological characteristics early advanced gallbladder carcinoma extrahepatic cholangiocarcinoma biliary tract cancer cancer gallbladder extrahepatic bile duct common malignancy biliary tract considered high grade malignancy study reviewed 293 gallbladder cancers 102 bile duct cancers clarifying growth invasion extrahepatic bile duct cancer 10 5 9 86 early gallbladder cancers showed lymphatic invasion neither venous invasion lymph node metastasis noted early cancers 70 6 207 293 gallbladder cases pt2 3 cancers frequently showed lymphatic venous perineural invasion lymph node metastasis 12 7 13 102 extrahepatic bile duct cancers ptis pt1 cancers categorized early cancers 15 4 2 13 early cancer showed vascular perineural invasion lymph node metastasis majority 87 3 extrahepatic bile duct cases pt2 3 cancers frequently showed vascular perineural invasion lymph node metastasis also examined intramural invasion patterns e intramural invasion patterns defined infiltrative growth ig type destructive growth dg type overall survival rate gallbladder cancer patients dg type significantly lower patients ig type associated frequent lymphatic venous invasion lymph node metastasis therefore pathological characteristics important clinical manifestation gallbladder extrahepatic bile duct cancers stn","probabilities":0.9799733,"Title":"Pathological Characteristics Of Early To Advanced Gallbladder Carcinoma And Extrahepatic Cholangiocarcinoma","Abstract":"Biliary tract cancer (cancer of gallbladder and extrahepatic bile duct) is the most common malignancy of the biliary tract, and is considered to be a high-grade malignancy. In this study, we reviewed 293 gallbladder cancers and 102 bile duct cancers for clarifying growth and invasion of the extrahepatic bile duct cancer. Only 10.5% (9/86) of the early gallbladder cancers showed lymphatic invasion, but neither venous invasion nor lymph node metastasis was noted in the early cancers. 70.6% (207/293) of the gallbladder cases were pT2-3 cancers, and frequently showed lymphatic/venous/perineural invasion and/or lymph node metastasis. 12.7% (13/102) of the extrahepatic bile duct cancers were pTis or pT1 cancers, which were categorized as early cancers. Only 15.4% (2/13) of the early cancer showed vascular/perineural invasion and/or lymph node metastasis. The majority (87.3%) of the extrahepatic bile duct cases was pT2-3 cancers, and frequently showed vascular/perineural invasion and/or lymph node metastasis. We also examined intramural invasion patterns; i.e. intramural invasion patterns were defined as infiltrative growth (IG) type, and destructive growth (DG) type. The overall survival rate of the gallbladder cancer patients with the DG type was significantly lower than that of the patients with the IG type, associated with frequent lymphatic/venous invasion and/or lymph node metastasis. Therefore, pathological characteristics are important for clinical manifestation of the gallbladder/extrahepatic bile duct cancers.","Source":"STN","category":"HUMAN","training_data":"Pathological Characteristics Of Early To Advanced Gallbladder Carcinoma And Extrahepatic Cholangiocarcinoma Biliary tract cancer (cancer of gallbladder and extrahepatic bile duct) is the most common malignancy of the biliary tract, and is considered to be a high-grade malignancy. In this study, we reviewed 293 gallbladder cancers and 102 bile duct cancers for clarifying growth and invasion of the extrahepatic bile duct cancer. Only 10.5% (9/86) of the early gallbladder cancers showed lymphatic invasion, but neither venous invasion nor lymph node metastasis was noted in the early cancers. 70.6% (207/293) of the gallbladder cases were pT2-3 cancers, and frequently showed lymphatic/venous/perineural invasion and/or lymph node metastasis. 12.7% (13/102) of the extrahepatic bile duct cancers were pTis or pT1 cancers, which were categorized as early cancers. Only 15.4% (2/13) of the early cancer showed vascular/perineural invasion and/or lymph node metastasis. The majority (87.3%) of the extrahepatic bile duct cases was pT2-3 cancers, and frequently showed vascular/perineural invasion and/or lymph node metastasis. We also examined intramural invasion patterns; i.e. intramural invasion patterns were defined as infiltrative growth (IG) type, and destructive growth (DG) type. The overall survival rate of the gallbladder cancer patients with the DG type was significantly lower than that of the patients with the IG type, associated with frequent lymphatic/venous invasion and/or lymph node metastasis. Therefore, pathological characteristics are important for clinical manifestation of the gallbladder/extrahepatic bile duct cancers. STN","prediction_labels":"HUMAN"},{"cleaned":"long non coding rna snhg1 affects cell proliferation migration epigenetically regulating il11 cdkn1a expression cholangiocarcinoma abstract available google scholar","probabilities":0.9467213,"Title":"Long Non-Coding Rna Snhg1 Affects Cell Proliferation And Migration By Epigenetically Regulating Il11 And Cdkn1A Expression In Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"ANIMAL","training_data":"Long Non-Coding Rna Snhg1 Affects Cell Proliferation And Migration By Epigenetically Regulating Il11 And Cdkn1A Expression In Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"predicting avoiding incidental gallbladder cancer background consequences incidental gallbladder cancer igbc following cholecystectomy may include repeat operation depending stage worse survival bile spillage occurred avoidable igbc suspected preoperatively methods retrospective single institution review done ultrasound images cases controls blindly reviewed radiologist chi square student tests well logistic regression kaplan meier analyses used p 0 01 considered significant results among 5796 cholecystectomies performed 2000 2013 26 0 45 igbc cases patients older 75 61 versus 52 27 years laparoscopic open conversions 23 1 versus 3 9 underwent imaging tests larger common bile duct diameter 7 13 versus 5 04 mm higher alkaline phosphatase ultrasound imaging showed gallbladder wall thickening gbwt without pericholecystic fluid pccf focal versus diffuse gbwt associated significantly igbc 73 9 versus 47 4 multivariable logistic regression analysis gbwt without pccf age strongest predictors igbc consequences igbc depended significantly intraoperative bile spillage nearly patients developing carcinomatosis significantly worse survival conclusions besides age gbwt dilated common bile duct elevated alkaline phosphatase number preoperative imaging modalities presence gbwt without pccf useful predictors igbc bile spillage causes poor survival patients igbc stn","probabilities":0.9799733,"Title":"Predicting (Avoiding) Incidental Gallbladder Cancer","Abstract":"Background: Consequences of incidental gallbladder cancer (iGBC) following cholecystectomy may include repeat operation (depending on T stage) and worse survival (if bile spillage occurred), both avoidable if iGBC were suspected preoperatively. \r\n\r\n Methods: A retrospective single-institution review was done. Ultrasound images for cases and controls were blindly reviewed by a radiologist. Chi-square and Student's t tests, as well as logistic regression and Kaplan-Meier analyses were used. A P ≤ 0.01 was considered significant. \r\n\r\n Results: Among 5796 cholecystectomies performed 2000-2013, 26 (0.45%) were iGBC cases. These patients were older (75.61 versus 52.27 years), had more laparoscopic-to-open conversions (23.1% versus 3.9%), underwent more imaging tests, had larger common bile duct diameter (7.13 versus 5.04 mm) and higher alkaline phosphatase. Ultrasound imaging showed that gallbladder wall thickening (GBWT) without pericholecystic fluid (PCCF), but not focal-versus-diffuse GBWT, was associated significantly with iGBC (73.9% versus 47.4%). On multivariable logistic regression analysis, GBWT without PCCF, and age were the strongest predictors of iGBC. The consequences iGBC depended significantly on intraoperative bile spillage, with nearly all such patients developing carcinomatosis and significantly worse survival. \r\n\r\n Conclusions: Besides age, GBWT, dilated common bile duct, and elevated alkaline phosphatase, number of preoperative imaging modalities and the presence of GBWT without PCCF are useful predictors of iGBC. Bile spillage causes poor survival in patients with iGBC.","Source":"STN","category":"HUMAN","training_data":"Predicting (Avoiding) Incidental Gallbladder Cancer Background: Consequences of incidental gallbladder cancer (iGBC) following cholecystectomy may include repeat operation (depending on T stage) and worse survival (if bile spillage occurred), both avoidable if iGBC were suspected preoperatively. \r\n\r\n Methods: A retrospective single-institution review was done. Ultrasound images for cases and controls were blindly reviewed by a radiologist. Chi-square and Student's t tests, as well as logistic regression and Kaplan-Meier analyses were used. A P ≤ 0.01 was considered significant. \r\n\r\n Results: Among 5796 cholecystectomies performed 2000-2013, 26 (0.45%) were iGBC cases. These patients were older (75.61 versus 52.27 years), had more laparoscopic-to-open conversions (23.1% versus 3.9%), underwent more imaging tests, had larger common bile duct diameter (7.13 versus 5.04 mm) and higher alkaline phosphatase. Ultrasound imaging showed that gallbladder wall thickening (GBWT) without pericholecystic fluid (PCCF), but not focal-versus-diffuse GBWT, was associated significantly with iGBC (73.9% versus 47.4%). On multivariable logistic regression analysis, GBWT without PCCF, and age were the strongest predictors of iGBC. The consequences iGBC depended significantly on intraoperative bile spillage, with nearly all such patients developing carcinomatosis and significantly worse survival. \r\n\r\n Conclusions: Besides age, GBWT, dilated common bile duct, and elevated alkaline phosphatase, number of preoperative imaging modalities and the presence of GBWT without PCCF are useful predictors of iGBC. Bile spillage causes poor survival in patients with iGBC. STN","prediction_labels":"HUMAN"},{"cleaned":"optimal time interval re resection incidentally discovered gallbladder cancer multi institution analysis us extrahepatic biliary malignancy consortium importance current recommendation perform re resection select patients incidentally discovered gallbladder cancer optimal time interval re resection patient selection long term survival known objective assess association time interval initial cholecystectomy reoperation overall survival design setting participants cohort study conducted january 1 2000 december 31 2014 10 us academic institutions total 207 patients incidentally discovered gallbladder cancer underwent reoperation available data date initial cholecystectomy included exposures time interval initial cholecystectomy reoperation group less 4 weeks group b 4 8 weeks group c greater 8 weeks main outcomes measures primary outcome overall survival results 449 patients gallbladder cancer 207 cases 46 discovered incidentally underwent reoperation 3 different time intervals date original cholecystectomy group less 4 weeks 25 patients 12 b 4 8 weeks 91 patients 44 c 8 weeks 91 patients 44 mean sd ages patients groups b c 65 9 64 11 66 12 years respectively groups similar baseline demographics extent resection presence residual disease stage resection margin status lymph node involvement postoperative complications patients underwent reoperation 4 8 weeks longest median overall survival group b 40 4 months compared underwent early group 17 4 months late group c 22 4 months reoperation log rank p 03 group c time intervals vs group b presence residual disease r2 resection advanced stage lymph node involvement associated decreased overall survival univariable cox regression group hazard ratio 2 63 95 ci 1 25 5 54 group c hazard ratio 2 07 95 ci 1 17 3 66 time intervals vs group b r2 resection hazard ratio 2 69 95 ci 1 27 5 69 advanced tstage hazard ratio 1 85 95 ci 1 11 3 08 persisted multivariable cox regression analysis conclusions relevance optimal time interval re resection incidentally discovered gallbladder cancer appears 4 8 weeks initial cholecystectomy stn","probabilities":0.9799733,"Title":"The Optimal Time-Interval To Re-Resection For Incidentally Discovered Gallbladder Cancer: A Multi-Institution Analysis From The Us Extrahepatic Biliary Malignancy Consortium","Abstract":"Importance: The current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The optimal time interval for re-resection for both patient selection and long-term survival is not known. \n\n Objective: To assess the association of time interval from the initial cholecystectomy to reoperation with overall survival. \n\n Design, setting, and participants: This cohort study was conducted from January 1, 2000, to December 31, 2014 at 10 US academic institutions. A total of 207 patients with incidentally discovered gallbladder cancer who underwent reoperation and had available data on the date of their initial cholecystectomy were included. \n\n Exposures: Time interval from the initial cholecystectomy to reoperation: group A: less than 4 weeks; group B: 4 to 8 weeks; and group C: greater than 8 weeks. \n\n Main outcomes and measures: Primary outcome was overall survival. \n\n Results: Of 449 patients with gallbladder cancer, 207 cases (46%) were discovered incidentally and underwent reoperation at 3 different time intervals from the date of the original cholecystectomy: group A: less than 4 weeks (25 patients, 12%); B: 4 to 8 weeks (91 patients, 44%); C: more than 8 weeks (91 patients, 44%). The mean (SD) ages of patients in groups A, B, and C were 65 (9), 64 (11), and 66 (12) years, respectively. All groups were similar for baseline demographics, extent of resection, presence of residual disease, T stage, resection margin status, lymph node involvement, and postoperative complications. Patients who underwent reoperation between 4 and 8 weeks had the longest median overall survival (group B: 40.4 months) compared with those who underwent early (group A: 17.4 months) or late (group C: 22.4 months) reoperation (log-rank P = .03). Group A and C time intervals (vs group B), presence of residual disease, an R2 resection, advanced T stage, and lymph node involvement were associated with decreased overall survival on univariable Cox regression. Only group A (hazard ratio, 2.63; 95% CI, 1.25-5.54) and group C (hazard ratio, 2.07; 95% CI, 1.17-3.66) time intervals (vs group B), R2 resection (hazard ratio, 2.69; 95% CI, 1.27-5.69), and advanced Tstage (hazard ratio, 1.85; 95% CI, 1.11-3.08) persisted on multivariable Cox regression analysis. \n\n Conclusions and relevance: The optimal time interval for re-resection for incidentally discovered gallbladder cancer appears to be between 4 and 8 weeks after the initial cholecystectomy.","Source":"STN","category":"HUMAN","training_data":"The Optimal Time-Interval To Re-Resection For Incidentally Discovered Gallbladder Cancer: A Multi-Institution Analysis From The Us Extrahepatic Biliary Malignancy Consortium Importance: The current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The optimal time interval for re-resection for both patient selection and long-term survival is not known. \n\n Objective: To assess the association of time interval from the initial cholecystectomy to reoperation with overall survival. \n\n Design, setting, and participants: This cohort study was conducted from January 1, 2000, to December 31, 2014 at 10 US academic institutions. A total of 207 patients with incidentally discovered gallbladder cancer who underwent reoperation and had available data on the date of their initial cholecystectomy were included. \n\n Exposures: Time interval from the initial cholecystectomy to reoperation: group A: less than 4 weeks; group B: 4 to 8 weeks; and group C: greater than 8 weeks. \n\n Main outcomes and measures: Primary outcome was overall survival. \n\n Results: Of 449 patients with gallbladder cancer, 207 cases (46%) were discovered incidentally and underwent reoperation at 3 different time intervals from the date of the original cholecystectomy: group A: less than 4 weeks (25 patients, 12%); B: 4 to 8 weeks (91 patients, 44%); C: more than 8 weeks (91 patients, 44%). The mean (SD) ages of patients in groups A, B, and C were 65 (9), 64 (11), and 66 (12) years, respectively. All groups were similar for baseline demographics, extent of resection, presence of residual disease, T stage, resection margin status, lymph node involvement, and postoperative complications. Patients who underwent reoperation between 4 and 8 weeks had the longest median overall survival (group B: 40.4 months) compared with those who underwent early (group A: 17.4 months) or late (group C: 22.4 months) reoperation (log-rank P = .03). Group A and C time intervals (vs group B), presence of residual disease, an R2 resection, advanced T stage, and lymph node involvement were associated with decreased overall survival on univariable Cox regression. Only group A (hazard ratio, 2.63; 95% CI, 1.25-5.54) and group C (hazard ratio, 2.07; 95% CI, 1.17-3.66) time intervals (vs group B), R2 resection (hazard ratio, 2.69; 95% CI, 1.27-5.69), and advanced Tstage (hazard ratio, 1.85; 95% CI, 1.11-3.08) persisted on multivariable Cox regression analysis. \n\n Conclusions and relevance: The optimal time interval for re-resection for incidentally discovered gallbladder cancer appears to be between 4 and 8 weeks after the initial cholecystectomy. STN","prediction_labels":"HUMAN"},{"cleaned":"ratio metastatic examined lymph nodes independent prognostic factor patients resectable middle distal bile duct carcinoma background lymph node ratio defined ratio number lymph node metastasis total number lymph nodes examined reported important prognostic factor gastrointestinal carcinomas except middle distal bile duct carcinomas methods 1991 2004 62 consecutive patients underwent surgery middle distal bile duct carcinoma retrospectively analyzed concerning prognostic factors results median number lymph nodes examined 12 range 5 38 overall 5 year survival rates patients lymph node ratio 0 lymph node ratio 0 2 lymph node ratio 2 62 41 0 respectively multivariate analysis revealed lymph node ratio 2 perineural invasion independent predictive factors survival conclusions lymph node ratio 2 important factor predict survival resected middle distal bile duct carcinoma stn","probabilities":0.9799733,"Title":"The Ratio Between Metastatic And Examined Lymph Nodes Is An Independent Prognostic Factor For Patients With Resectable Middle And Distal Bile Duct Carcinoma","Abstract":"Background: The lymph node ratio, defined as the ratio between the number of lymph node metastasis and the total number of lymph nodes examined, has been reported to be an important prognostic factor in other gastrointestinal carcinomas except middle and distal bile duct carcinomas. \r\n\r\n Methods: Between 1991 and 2004, 62 consecutive patients who underwent surgery for middle and distal bile duct carcinoma were retrospectively analyzed concerning prognostic factors. \r\n\r\n Results: The median number of lymph nodes examined was 12 (range 5 to 38). The overall 5-year survival rates of patients with lymph node ratio of 0, lymph node ratio of 0 to .2, and lymph node ratio >.2 were 62%, 41%, and 0%, respectively. A multivariate analysis revealed that a lymph node ratio >.2 and perineural invasion were independent predictive factors for survival. \r\n\r\n Conclusions: Lymph node ratio >.2 is an important factor to predict survival after resected middle and distal bile duct carcinoma.","Source":"STN","category":"HUMAN","training_data":"The Ratio Between Metastatic And Examined Lymph Nodes Is An Independent Prognostic Factor For Patients With Resectable Middle And Distal Bile Duct Carcinoma Background: The lymph node ratio, defined as the ratio between the number of lymph node metastasis and the total number of lymph nodes examined, has been reported to be an important prognostic factor in other gastrointestinal carcinomas except middle and distal bile duct carcinomas. \r\n\r\n Methods: Between 1991 and 2004, 62 consecutive patients who underwent surgery for middle and distal bile duct carcinoma were retrospectively analyzed concerning prognostic factors. \r\n\r\n Results: The median number of lymph nodes examined was 12 (range 5 to 38). The overall 5-year survival rates of patients with lymph node ratio of 0, lymph node ratio of 0 to .2, and lymph node ratio >.2 were 62%, 41%, and 0%, respectively. A multivariate analysis revealed that a lymph node ratio >.2 and perineural invasion were independent predictive factors for survival. \r\n\r\n Conclusions: Lymph node ratio >.2 is an important factor to predict survival after resected middle and distal bile duct carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"opisthorchiasis induced cholangiocarcinoma innate immunity may cause cancer innate inflammatory responses towards persistent opisthorchis viverrini ov infection likely contribute development cholangiocarcinoma cca liver cancer rare west prevalent greater mekong subregion countries southeast asia infection results infiltration innate immune cells bile ducts subsequent activation inflammatory immune responses fail clear ov instead may damage local tissues within bile ducts patients infected ov develop cca tumourigenesis may dependent multiple factors including magnitude inflammatory response activated infected individuals purpose review summarize innate immune responses may promote tumourigenesis following ov infection responses used predict cca onset ov infected individuals also hypothesizes role helicobacterspp associated liver fluke infections may play activation innate immune system promote tissue damage persistent inflammation leading cca pubmed","probabilities":0.88235295,"Title":"Opisthorchiasis-Induced Cholangiocarcinoma: How Innate Immunity May Cause Cancer","Abstract":"Innate, inflammatory responses towards persistent Opisthorchis viverrini (OV) infection are likely to contribute to the development of cholangiocarcinoma (CCA), a liver cancer that is rare in the West but prevalent in Greater Mekong Subregion countries in Southeast Asia. Infection results in the infiltration of innate immune cells into the bile ducts and subsequent activation of inflammatory immune responses that fail to clear OV but instead may damage local tissues within the bile ducts. Not all patients infected with OV develop CCA, and so tumourigenesis may be dependent on multiple factors including the magnitude of the inflammatory response that is activated in infected individuals. The purpose of this review is to summarize how innate immune responses may promote tumourigenesis following OV infection and if such responses can be used to predict CCA onset in OV-infected individuals. It also hypothesizes on the role that Helicobacterspp., which are associated with liver fluke infections, may play in activation of the innate the immune system to promote tissue damage and persistent inflammation leading to CCA.","Source":"PubMed","category":"HUMAN","training_data":"Opisthorchiasis-Induced Cholangiocarcinoma: How Innate Immunity May Cause Cancer Innate, inflammatory responses towards persistent Opisthorchis viverrini (OV) infection are likely to contribute to the development of cholangiocarcinoma (CCA), a liver cancer that is rare in the West but prevalent in Greater Mekong Subregion countries in Southeast Asia. Infection results in the infiltration of innate immune cells into the bile ducts and subsequent activation of inflammatory immune responses that fail to clear OV but instead may damage local tissues within the bile ducts. Not all patients infected with OV develop CCA, and so tumourigenesis may be dependent on multiple factors including the magnitude of the inflammatory response that is activated in infected individuals. The purpose of this review is to summarize how innate immune responses may promote tumourigenesis following OV infection and if such responses can be used to predict CCA onset in OV-infected individuals. It also hypothesizes on the role that Helicobacterspp., which are associated with liver fluke infections, may play in activation of the innate the immune system to promote tissue damage and persistent inflammation leading to CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"characterization prognostic factors efficacy adjuvant 1 chemotherapy patients post surgery extrahepatic bile duct cancer background aim clear consensus type adjuvant therapy used patients extrahepatic bile duct cancer patients methods two hundred seventy one patients undergone surgical resection extrahepatic bile duct cancer composed study cohort demographics treatments relationships potential prognostic factors survival rates analyzed results overall 3 year 5 year survival rates post surgery extrahepatic bile duct cancer patients 49 0 35 4 respectively multivariate analysis revealed regional lymph node metastasis independent negative prognostic factor observed significant correlation node positive extrahepatic bile duct cancer postoperative local recurrence liver metastasis peritoneal dissemination post surgery lymph node metastasis adjuvant 1 chemotherapy showed favorable hazard ratio patients lymph node metastases positive vascular invasion conclusion recommend use adjuvant 1 therapy patients lymph node metastases microvascular invasion pubmed","probabilities":0.9799733,"Title":"Characterization of Prognostic Factors and the Efficacy of Adjuvant S-1 Chemotherapy in Patients with Post-surgery Extrahepatic Bile Duct Cancer","Abstract":"BACKGROUND/AIM: There is no clear consensus on the type of adjuvant therapy that should be used for patients with extrahepatic bile duct cancer. PATIENTS AND METHODS: Two hundred and seventy-one patients that had undergone surgical resection for extrahepatic bile duct cancer composed the study cohort. Demographics, treatments, and relationships between the potential prognostic factors and survival rates were analyzed. RESULTS: The overall 3-year and 5-year survival rates for post-surgery extrahepatic bile duct cancer patients were 49.0% and 35.4%, respectively. Multivariate analysis revealed that regional lymph node metastasis was an independent negative prognostic factor. We observed a significant correlation between node-positive extrahepatic bile duct cancer and postoperative local recurrence, liver metastasis, peritoneal dissemination, and post-surgery lymph node metastasis. Adjuvant S-1 chemotherapy showed a favorable hazard ratio in patients with lymph node metastases or positive vascular invasion. CONCLUSION: We recommend the use of adjuvant S-1 therapy in patients with lymph node metastases or microvascular invasion.","Source":"PubMed","category":"HUMAN","training_data":"Characterization of Prognostic Factors and the Efficacy of Adjuvant S-1 Chemotherapy in Patients with Post-surgery Extrahepatic Bile Duct Cancer BACKGROUND/AIM: There is no clear consensus on the type of adjuvant therapy that should be used for patients with extrahepatic bile duct cancer. PATIENTS AND METHODS: Two hundred and seventy-one patients that had undergone surgical resection for extrahepatic bile duct cancer composed the study cohort. Demographics, treatments, and relationships between the potential prognostic factors and survival rates were analyzed. RESULTS: The overall 3-year and 5-year survival rates for post-surgery extrahepatic bile duct cancer patients were 49.0% and 35.4%, respectively. Multivariate analysis revealed that regional lymph node metastasis was an independent negative prognostic factor. We observed a significant correlation between node-positive extrahepatic bile duct cancer and postoperative local recurrence, liver metastasis, peritoneal dissemination, and post-surgery lymph node metastasis. Adjuvant S-1 chemotherapy showed a favorable hazard ratio in patients with lymph node metastases or positive vascular invasion. CONCLUSION: We recommend the use of adjuvant S-1 therapy in patients with lymph node metastases or microvascular invasion. PubMed","prediction_labels":"HUMAN"},{"cleaned":"identification micrornas associated survival patients gallbladder carcinoma objective study investigated micro mi rnas associated survival patients gallbladder carcinoma gbc methods mirna expression profiling carried 40 cancerous tissues gbc patients long term n 20 short term n 20 survival eight healthy gallbladder tissues gene expression omnibus database mirnas dysregulated gbc patients long term short term survival identified using geo2r venndiagram packages analyzed mirna target prediction tools clusterprofiler package results compared healthy gallbladder tissues 104 124 mirnas dysregulated cancerous tissues gbc patients long term survival short term survival respectively two mirnas hsa mir 142 5p hsa mir 146b 5p 22 mirnas hsa mir 30a 3p hsa mir 660 5p hsa mir 338 3p exclusively dysregulated gbc patients long term short term survival respectively enrichment analysis revealed mirnas exclusively dysregulated gbc patients short term survival involved 46 biological processes 10 cellular components 11 molecular functions 44 pathways morphogenesis epithelium response transforming growth factor beta heterochromatin phosphatase binding conclusion study identified promising biomarkers predicting survival gbc patients also contributed understanding pathogenesis prognosis gbc google scholar","probabilities":0.88235295,"Title":"Identification Of Micrornas Associated With The Survival Of Patients With Gallbladder Carcinoma","Abstract":"Objective\nThis study investigated micro (mi)RNAs associated with the survival of patients with gallbladder carcinoma (GBC).\n\nMethods\nmiRNA expression profiling was carried out of 40 cancerous tissues from GBC patients with long-term (n = 20) and short-term (n = 20) survival and eight healthy gallbladder tissues from the Gene Expression Omnibus database. miRNAs dysregulated in GBC patients with long-term or short-term survival were identified using GEO2R and VennDiagram packages, and analyzed by miRNA target prediction tools and the clusterProfiler package.\n\nResults\nCompared with healthy gallbladder tissues, 104 and 124 miRNAs were dysregulated in cancerous tissues of GBC patients with long-term survival and short-term survival, respectively. Two miRNAs (hsa-miR-142-5p and hsa-miR-146b-5p) and 22 miRNAs (such as hsa-miR-30a-3p, hsa-miR-660-5p, and hsa-miR-338-3p) were exclusively dysregulated in GBC patients with long-term and short-term survival, respectively. Enrichment analysis revealed that miRNAs exclusively dysregulated in GBC patients with short-term survival were involved in 46 biological processes, 10 cellular components, 11 molecular functions, and 44 pathways such as morphogenesis of an epithelium, response to transforming growth factor beta, heterochromatin, and phosphatase binding.\n\nConclusion\nThis study not only identified some promising biomarkers for predicting survival in GBC patients, but also contributed to our understanding of the pathogenesis and prognosis of GBC.","Source":"Google Scholar","category":"HUMAN","training_data":"Identification Of Micrornas Associated With The Survival Of Patients With Gallbladder Carcinoma Objective\nThis study investigated micro (mi)RNAs associated with the survival of patients with gallbladder carcinoma (GBC).\n\nMethods\nmiRNA expression profiling was carried out of 40 cancerous tissues from GBC patients with long-term (n = 20) and short-term (n = 20) survival and eight healthy gallbladder tissues from the Gene Expression Omnibus database. miRNAs dysregulated in GBC patients with long-term or short-term survival were identified using GEO2R and VennDiagram packages, and analyzed by miRNA target prediction tools and the clusterProfiler package.\n\nResults\nCompared with healthy gallbladder tissues, 104 and 124 miRNAs were dysregulated in cancerous tissues of GBC patients with long-term survival and short-term survival, respectively. Two miRNAs (hsa-miR-142-5p and hsa-miR-146b-5p) and 22 miRNAs (such as hsa-miR-30a-3p, hsa-miR-660-5p, and hsa-miR-338-3p) were exclusively dysregulated in GBC patients with long-term and short-term survival, respectively. Enrichment analysis revealed that miRNAs exclusively dysregulated in GBC patients with short-term survival were involved in 46 biological processes, 10 cellular components, 11 molecular functions, and 44 pathways such as morphogenesis of an epithelium, response to transforming growth factor beta, heterochromatin, and phosphatase binding.\n\nConclusion\nThis study not only identified some promising biomarkers for predicting survival in GBC patients, but also contributed to our understanding of the pathogenesis and prognosis of GBC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"whole exome sequencing analysis identifies recurrent mutation rate bap1 gene intrahepatic cholangiocarcinoma patients exposed asbestos background past three decades registered progressive worldwide increase incidence intra hepatic cholangiocarcinoma icc amalignancy arising biliary tree within liver recently two case control studies one retrospective one prospective observed 4 8 a7 fold respectively increased risk icc workers exposed toasbestos thesefindings stronglysuggesta putative role asbestos icc carcinogenesisand possibly itsincreasing incidence since identification environmental diseases isgainingincreasing attention high impact public health present study aimed toidentify putative molecular biomarkers asbestos drivenicc carcinogenesis material methods atotal 22 icc patients enrolled eachpatient data established suspected icc risk factors collected asbestos exposure assessed modified renam questionnaire basisof modified renam questionnaire patients dividedin two groups asbestos exposed controlgroup exposed whole exome sequencing wes performedon dna 22 tumors matchedblood samples somatic single nucleotidevariants insertionsand deletions identified functionally annotated mutatedgenes interestwere selected according tothe frequency mutations withinthe asbestos exposed patients subgroup based priori knowledge cancer relatedgenes particular attention ones already reported mutated high recurrence malignant pleuric mesothelioma mpm classic model asbestos related cancer results according renam questionnaire 10 45 of22 icc patients resulted exposed toasbestos wes analysis revealedafrequency 27 6 22 somatic mutation brca1 associated protein 1 bap1 corresponding 5over 10 asbestos exposed icc patients 50 andto1 12 exposed 5 according chi square test bap1 alterations significantly associated asbestos exposure p value 0 0289 conclusions bap1 mutation occurred high recurrence rate asbestos exposed icc patients already reported mpm serve aputative candidate genetic alterations associated asbestos exposure malignancy studies based alargerpatients population needed confirm preliminary finding google scholar","probabilities":0.9799733,"Title":"Whole-Exome Sequencing Analysis Identifies Recurrent Mutation Rate In Bap1 Gene In Intrahepatic Cholangiocarcinoma Patients Exposed To Asbestos","Abstract":"Background: The past three decades have registered a progressive worldwide increase in incidence of intra-hepatic cholangiocarcinoma (ICC),amalignancy arising from the biliary tree within the liver. Recently, in two case-control studies (one retrospective and one prospective), we observed a 4.8-and a7-fold, respectively, increased risk of ICC in workers exposed toasbestos. Thesefindings stronglysuggesta putative role of asbestos in ICC carcinogenesisand, possibly,in itsincreasing incidence.Since the identification of environmental diseases isgainingincreasing attention because of their high impact on public health, the present study aimed toidentify putative molecular biomarkers of asbestos-drivenICC carcinogenesis. Material and methods: Atotal of 22 ICC patients were enrolled.For eachpatient, data on established or suspected ICC risk factors were collected; asbestos exposure was assessed by modified ReNaM questionnaire. On the basisof modified ReNaM questionnaire, patients were dividedin two groups: asbestos-exposed and the controlgroup of not-exposed. Whole exome sequencing (WES) was performedon DNA from 22 tumors and matchedblood samples. Somatic single nucleotidevariants,insertionsand deletions were identified and functionally annotated.Mutatedgenes of interestwere selected according tothe frequency of mutations withinthe asbestos-exposed patients’ subgroup and based on a priori knowledge about cancer-relatedgenes, with particular attention for those ones already reported to be mutated with high recurrence in malignant pleuric mesothelioma(MPM),a classic model of asbestos-related cancer. Results: According to ReNaM questionnaire, 10 (45%) out of22 ICC patients resulted exposed toasbestos. WES analysis revealedafrequency of 27% (6 over 22)of somatic mutation in BRCA1 associated protein -1(BAP1),corresponding to 5over 10 of asbestos-exposed ICC patients (50%)andto1 over 12 of not exposed (5%). According to chi-square test, BAP1 alterations were significantly associated with asbestos exposure (p-value¼0.0289). Conclusions: BAP1 mutation occurred with a high recurrence rate in asbestos-exposed ICC patients and, as already reported in MPM, could serve as aputative candidate for genetic alterations associated with asbestos exposure in this malignancy.Further studies based on alargerpatients population are needed to confirm this preliminary finding.","Source":"Google Scholar","category":"HUMAN","training_data":"Whole-Exome Sequencing Analysis Identifies Recurrent Mutation Rate In Bap1 Gene In Intrahepatic Cholangiocarcinoma Patients Exposed To Asbestos Background: The past three decades have registered a progressive worldwide increase in incidence of intra-hepatic cholangiocarcinoma (ICC),amalignancy arising from the biliary tree within the liver. Recently, in two case-control studies (one retrospective and one prospective), we observed a 4.8-and a7-fold, respectively, increased risk of ICC in workers exposed toasbestos. Thesefindings stronglysuggesta putative role of asbestos in ICC carcinogenesisand, possibly,in itsincreasing incidence.Since the identification of environmental diseases isgainingincreasing attention because of their high impact on public health, the present study aimed toidentify putative molecular biomarkers of asbestos-drivenICC carcinogenesis. Material and methods: Atotal of 22 ICC patients were enrolled.For eachpatient, data on established or suspected ICC risk factors were collected; asbestos exposure was assessed by modified ReNaM questionnaire. On the basisof modified ReNaM questionnaire, patients were dividedin two groups: asbestos-exposed and the controlgroup of not-exposed. Whole exome sequencing (WES) was performedon DNA from 22 tumors and matchedblood samples. Somatic single nucleotidevariants,insertionsand deletions were identified and functionally annotated.Mutatedgenes of interestwere selected according tothe frequency of mutations withinthe asbestos-exposed patients’ subgroup and based on a priori knowledge about cancer-relatedgenes, with particular attention for those ones already reported to be mutated with high recurrence in malignant pleuric mesothelioma(MPM),a classic model of asbestos-related cancer. Results: According to ReNaM questionnaire, 10 (45%) out of22 ICC patients resulted exposed toasbestos. WES analysis revealedafrequency of 27% (6 over 22)of somatic mutation in BRCA1 associated protein -1(BAP1),corresponding to 5over 10 of asbestos-exposed ICC patients (50%)andto1 over 12 of not exposed (5%). According to chi-square test, BAP1 alterations were significantly associated with asbestos exposure (p-value¼0.0289). Conclusions: BAP1 mutation occurred with a high recurrence rate in asbestos-exposed ICC patients and, as already reported in MPM, could serve as aputative candidate for genetic alterations associated with asbestos exposure in this malignancy.Further studies based on alargerpatients population are needed to confirm this preliminary finding. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"frequency significance igg4 immunohistochemical staining liver explants patients primary sclerosing cholangitis dense tissue infiltrates igg4 plasma cells 50 high powered field hpf purportedly highly specific igg4 related disease however frequency significance liver infiltrating igg4 plasma cells primary sclerosing cholangitis psc applying cut offs determined sought determine incidence intrahepatic igg4 positive staining psc patients undergoing transplantation correlating findings clinical parameters immunohistochemical staining performed liver explants obtained 1991 2009 122 explants obtained hilar igg4 staining found mild 10 29 igg4 cells hpf 23 0 moderate 30 50 hpf 9 0 marked 50 hpf 15 6 marked hilar lymphoplasmacytic infiltration significantly associated marked hilar igg4 staining p 0 001 patient marked peripheral igg4 staining although mild moderate staining observed 24 5 3 3 respectively marked hilar igg4 staining significantly associated presence dominant biliary strictures p 0 01 need biliary stenting p 0 001 however exist significant differences age psc diagnosis presence inflammatory bowel disease extrahepatic autoimmune disease frequency cholangiocarcinoma interval diagnosis transplantation post transplant psc recurrence survival 51 control liver sections pbc 18 hcv 19 hbv 8 aih 6 none marked moderate hilar igg4 staining whereas mild staining seen 10 p 0 001 marked 50 hpf hilar igg4 lymphoplasmacytic infiltration frequently observed psc associated presence dominant biliary strictures however unlike serum igg4 seemingly associate clinical disease course stn","probabilities":0.7966102,"Title":"Frequency And Significance Of Igg4 Immunohistochemical Staining In Liver Explants From Patients With Primary Sclerosing Cholangitis","Abstract":"Dense tissue infiltrates of IgG4(+) plasma cells >50/high-powered field (HPF) are purportedly highly specific for IgG4-related disease. However, the frequency and significance of liver-infiltrating IgG4(+) plasma cells in primary sclerosing cholangitis (PSC) applying these cut-offs has not been determined. We sought to determine the incidence of intrahepatic IgG4-positive staining in PSC patients undergoing transplantation, correlating findings with clinical parameters. Immunohistochemical staining was performed on liver explants obtained between 1991 and 2009. Of 122 explants obtained, hilar IgG4(+) staining was found to be mild (10-29 IgG4(+) cells/HPF) in 23.0%, moderate (30-50/HPF) in 9.0% and marked (>50/HPF) in 15.6%. Marked hilar lymphoplasmacytic infiltration was significantly associated with marked hilar IgG4(+) staining (P < 0.001). No patient had marked peripheral IgG4(+) staining, although mild and moderate staining was observed in 24.5% and 3.3% respectively. Marked hilar IgG4(+) staining was significantly associated with the presence of dominant biliary strictures (P = 0.01) and need for biliary stenting (P = 0.001). There did not, however, exist any significant differences in the age at PSC diagnosis, presence of inflammatory bowel disease or extrahepatic autoimmune disease, frequency of cholangiocarcinoma, interval between diagnosis and transplantation, or post-transplant PSC recurrence or survival. Of 51 control liver sections (PBC = 18; HCV = 19; HBV = 8; AIH = 6), none had marked or moderate hilar IgG4(+) staining, whereas mild staining was seen in only 10% (P < 0.001). Marked (>50/HPF) hilar IgG4(+) lymphoplasmacytic infiltration is frequently observed in PSC and associated with the presence of dominant biliary strictures. However, unlike serum IgG4(+) , this does not seemingly associate with clinical disease course.","Source":"STN","category":"ANIMAL","training_data":"Frequency And Significance Of Igg4 Immunohistochemical Staining In Liver Explants From Patients With Primary Sclerosing Cholangitis Dense tissue infiltrates of IgG4(+) plasma cells >50/high-powered field (HPF) are purportedly highly specific for IgG4-related disease. However, the frequency and significance of liver-infiltrating IgG4(+) plasma cells in primary sclerosing cholangitis (PSC) applying these cut-offs has not been determined. We sought to determine the incidence of intrahepatic IgG4-positive staining in PSC patients undergoing transplantation, correlating findings with clinical parameters. Immunohistochemical staining was performed on liver explants obtained between 1991 and 2009. Of 122 explants obtained, hilar IgG4(+) staining was found to be mild (10-29 IgG4(+) cells/HPF) in 23.0%, moderate (30-50/HPF) in 9.0% and marked (>50/HPF) in 15.6%. Marked hilar lymphoplasmacytic infiltration was significantly associated with marked hilar IgG4(+) staining (P < 0.001). No patient had marked peripheral IgG4(+) staining, although mild and moderate staining was observed in 24.5% and 3.3% respectively. Marked hilar IgG4(+) staining was significantly associated with the presence of dominant biliary strictures (P = 0.01) and need for biliary stenting (P = 0.001). There did not, however, exist any significant differences in the age at PSC diagnosis, presence of inflammatory bowel disease or extrahepatic autoimmune disease, frequency of cholangiocarcinoma, interval between diagnosis and transplantation, or post-transplant PSC recurrence or survival. Of 51 control liver sections (PBC = 18; HCV = 19; HBV = 8; AIH = 6), none had marked or moderate hilar IgG4(+) staining, whereas mild staining was seen in only 10% (P < 0.001). Marked (>50/HPF) hilar IgG4(+) lymphoplasmacytic infiltration is frequently observed in PSC and associated with the presence of dominant biliary strictures. However, unlike serum IgG4(+) , this does not seemingly associate with clinical disease course. STN","prediction_labels":"HUMAN"},{"cleaned":"bcl6 overexpression associated decreased p19 arf expression confers independent prognosticator gallbladder carcinoma b cell lymphoma 6 bcl6 protein vital lymphogenesis expression well established lymphoma especially diffuse large b cell lymphoma role carcinogenesis less well understood previous study shows bcl6 expression may regulate p19 functions important regulator p53 pathway prior study attempted evaluate significance bcl6 p19 arf expression large cohort patients gallbladder carcinomas gbcs selected 164 patients gbc performed immunostains bcl6 p19 arf bcl6 expression p19 arf expression evaluated using histochemical score h score correlated results various clinicopathological factors disease specific survival dss disease free survival dfs bcl6 overexpression significantly associated high pt status high tnm stage higher histological grade p 0 029 vascular invasion perineurial invasion high ki 67 labeling index low p19 expression importantly bcl6 overexpression gbc strongly associated worse dss p 0 0001 dfs p 0 0001 univariate analysis remained independently predictive adverse outcomes p 0 001 hazard ratio h r 3 098 dss p 0 002 h r 2 255 dfs low p19 arf expression correlated poor dss p 0 0144 dfs p 0 0032 univariate analysis prognosticatory multivariate analysis gbc bcl6 overexpression correlated adverse phenotypes decreased p19 arf expression bcl6 overexpression also independently predicts worse dss dfs suggesting role tumorigenesis carcinogenesis potential prognostic indicator gbc pubmed","probabilities":0.962963,"Title":"BCL6 overexpression is associated with decreased p19 ARF expression and confers an independent prognosticator in gallbladder carcinoma","Abstract":"B cell lymphoma 6 (BCL6) is a protein that is vital for lymphogenesis. Its expression has been well established in lymphoma, especially in diffuse large B-cell lymphoma. Its role in carcinogenesis is less well understood. Previous study shows that BCL6 expression may regulate p19 functions, an important regulator for the p53 pathway. No prior study has attempted to evaluate the significance of BCL6 and p19(ARF) expression in a large cohort of patients with gallbladder carcinomas (GBCs). We selected 164 patients with GBC and performed immunostains for BCL6 and p19(ARF). BCL6 expression and p19(ARF) expression were evaluated using a histochemical score (H-score). We then correlated the results with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS). BCL6 overexpression was significantly associated with high pT status, high TNM stage, higher histological grade (p = 0.029), vascular invasion, perineurial invasion, high Ki-67 labeling index, and low p19 expression. Importantly, BCL6 overexpression in GBC was strongly associated with worse DSS (p < 0.0001) and DFS (p < 0.0001) in the univariate analysis, and remained independently predictive of adverse outcomes (p = 0.001, hazard ratio (H.R.) = 3.098 for DSS; p = 0.002, H.R. = 2.255 for DFS). Low p19(ARF) expression was correlated with a poor DSS (p = 0.0144) and DFS (p = 0.0032) in the univariate analysis but was not prognosticatory in the multivariate analysis. In GBC, BCL6 overexpression correlated with adverse phenotypes and decreased p19(ARF) expression. BCL6 overexpression also independently predicts worse DSS and DFS, suggesting it has a role in tumorigenesis or carcinogenesis and could be a potential prognostic indicator in GBC.","Source":"PubMed","category":"HUMAN","training_data":"BCL6 overexpression is associated with decreased p19 ARF expression and confers an independent prognosticator in gallbladder carcinoma B cell lymphoma 6 (BCL6) is a protein that is vital for lymphogenesis. Its expression has been well established in lymphoma, especially in diffuse large B-cell lymphoma. Its role in carcinogenesis is less well understood. Previous study shows that BCL6 expression may regulate p19 functions, an important regulator for the p53 pathway. No prior study has attempted to evaluate the significance of BCL6 and p19(ARF) expression in a large cohort of patients with gallbladder carcinomas (GBCs). We selected 164 patients with GBC and performed immunostains for BCL6 and p19(ARF). BCL6 expression and p19(ARF) expression were evaluated using a histochemical score (H-score). We then correlated the results with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS). BCL6 overexpression was significantly associated with high pT status, high TNM stage, higher histological grade (p = 0.029), vascular invasion, perineurial invasion, high Ki-67 labeling index, and low p19 expression. Importantly, BCL6 overexpression in GBC was strongly associated with worse DSS (p < 0.0001) and DFS (p < 0.0001) in the univariate analysis, and remained independently predictive of adverse outcomes (p = 0.001, hazard ratio (H.R.) = 3.098 for DSS; p = 0.002, H.R. = 2.255 for DFS). Low p19(ARF) expression was correlated with a poor DSS (p = 0.0144) and DFS (p = 0.0032) in the univariate analysis but was not prognosticatory in the multivariate analysis. In GBC, BCL6 overexpression correlated with adverse phenotypes and decreased p19(ARF) expression. BCL6 overexpression also independently predicts worse DSS and DFS, suggesting it has a role in tumorigenesis or carcinogenesis and could be a potential prognostic indicator in GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"optimal surgical treatment patients t1b gallbladder cancer international multicenter study background consensus optimal treatment t1b gallbladder cancer gbc due lack evidence difficulty anatomy pathological standardization methods total 272 patients t1b gbc underwent surgical resection 14 centers specialized hepatobiliary pancreatic surgeons pathologists korea japan chile united states studied clinical outcomes including disease specific survival dss rates according types surgery analyzed results excluding patients 237 qualifying patients consisted 90 men 147 women simple cholecystectomy sc performed 116 patients 48 9 extended cholecystectomy ec 121 patients 51 1 overall 5 year dss 94 6 similar sc ec patients 93 7 vs 95 5 p 0 496 5 year dss similar sc ec patients america 82 3 vs 100 0 p 0 249 well asia 98 6 vs 95 2 p 0 690 5 year dss also differ according lymph node metastasis p 0 688 tumor location p 0 474 conclusions sc showed similar clinical outcomes including recurrence survival outcomes ec therefore ec needed treatment t1b gbc pubmed","probabilities":0.9799733,"Title":"Optimal surgical treatment in patients with T1b gallbladder cancer: An international multicenter study","Abstract":"BACKGROUND: There is no consensus on the optimal treatment of T1b gallbladder cancer (GBC) due to the lack of evidence and the difficulty of anatomy and pathological standardization. METHODS: A total of 272 patients with T1b GBC who underwent surgical resection at 14 centers with specialized hepatobiliary-pancreatic surgeons and pathologists in Korea, Japan, Chile, and the United States were studied. Clinical outcomes including disease-specific survival (DSS) rates according to the types of surgery were analyzed. RESULTS: After excluding patients, the 237 qualifying patients consisted of 90 men and 147 women. Simple cholecystectomy (SC) was performed in 116 patients (48.9%) and extended cholecystectomy (EC) in 121 patients (51.1%). The overall 5-year DSS was 94.6%, and it was similar between SC and EC patients (93.7% vs. 95.5%, P = 0.496). The 5-year DSS was similar between SC and EC patients in America (82.3% vs. 100.0%, P = 0.249) as well as in Asia (98.6% vs. 95.2%, P = 0.690). The 5-year DSS also did not differ according to lymph node metastasis (P = 0.688) or tumor location (P = 0.474). CONCLUSIONS: SC showed similar clinical outcomes (including recurrence) and survival outcomes as EC; therefore, EC is not needed for the treatment of T1b GBC.","Source":"PubMed","category":"HUMAN","training_data":"Optimal surgical treatment in patients with T1b gallbladder cancer: An international multicenter study BACKGROUND: There is no consensus on the optimal treatment of T1b gallbladder cancer (GBC) due to the lack of evidence and the difficulty of anatomy and pathological standardization. METHODS: A total of 272 patients with T1b GBC who underwent surgical resection at 14 centers with specialized hepatobiliary-pancreatic surgeons and pathologists in Korea, Japan, Chile, and the United States were studied. Clinical outcomes including disease-specific survival (DSS) rates according to the types of surgery were analyzed. RESULTS: After excluding patients, the 237 qualifying patients consisted of 90 men and 147 women. Simple cholecystectomy (SC) was performed in 116 patients (48.9%) and extended cholecystectomy (EC) in 121 patients (51.1%). The overall 5-year DSS was 94.6%, and it was similar between SC and EC patients (93.7% vs. 95.5%, P = 0.496). The 5-year DSS was similar between SC and EC patients in America (82.3% vs. 100.0%, P = 0.249) as well as in Asia (98.6% vs. 95.2%, P = 0.690). The 5-year DSS also did not differ according to lymph node metastasis (P = 0.688) or tumor location (P = 0.474). CONCLUSIONS: SC showed similar clinical outcomes (including recurrence) and survival outcomes as EC; therefore, EC is not needed for the treatment of T1b GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer incidence mortality united states 1999 2011 background gallbladder cancer rare cancer unusual distribution population based estimates united states published methods using population based cancer incidence mortality data examined u gallbladder cancer incidence death rates 2007 2011 trends 1999 2011 results 2007 2011 approximately 3 700 persons diagnosed primary gallbladder cancer rate 1 13 cases per 100 000 2 000 died disease rate 0 62 deaths per 100 000 year united states two thirds gallbladder cancer cases deaths occurred among women gallbladder cancer incidence death rates three times higher among american indian alaska native persons non hispanic white persons state gallbladder cancer incidence death rates ranged 2 fold 1999 2011 gallbladder cancer incidence rates decreased among women remained level among men death rates declined among women stabilized among men declining 1999 2006 gallbladder cancer incidence rates increased subgroups notably among black persons aged 45 years endocrine tumors conclusions data u population based cancer registries confirm gallbladder cancer incidence death rates higher among women men highest among american indian alaska native persons differ region overall incidence death rates decreased 1999 2011 incidence rates increased among small subgroups impact surveillance gallbladder cancer incidence mortality particularly monitor increases subgroups may provide clues etiology stimulate research stn","probabilities":0.9799733,"Title":"Gallbladder Cancer Incidence And Mortality United States 1999-2011","Abstract":"Background: Gallbladder cancer is a rare cancer with unusual distribution, and few population-based estimates for the United States have been published. \n\n Methods: Using population-based cancer incidence and mortality data, we examined U.S. gallbladder cancer incidence and death rates for 2007-2011 and trends for 1999-2011. \n\n Results: During 2007 to 2011, approximately 3,700 persons were diagnosed with primary gallbladder cancer (rate = 1.13 cases per 100,000) and 2,000 died from the disease (rate = 0.62 deaths per 100,000) each year in the United States. Two thirds of gallbladder cancer cases and deaths occurred among women. Gallbladder cancer incidence and death rates were three times higher among American Indian and Alaska Native persons than non-Hispanic white persons. By state, gallbladder cancer incidence and death rates ranged by about 2-fold. During 1999 to 2011, gallbladder cancer incidence rates decreased among women but remained level among men; death rates declined among women but stabilized among men after declining from 1999 to 2006. Gallbladder cancer incidence rates increased in some subgroups, notably among black persons, those aged <45 years, and for endocrine tumors. \n\n Conclusions: Data from U.S. population-based cancer registries confirm that gallbladder cancer incidence and death rates are higher among women than men, highest among American Indian and Alaska Native persons, and differ by region. While overall incidence and death rates decreased during 1999 to 2011, incidence rates increased among some small subgroups. \n\n Impact: Surveillance of gallbladder cancer incidence and mortality, particularly to monitor increases in subgroups, may provide clues to etiology and stimulate further research.","Source":"STN","category":"HUMAN","training_data":"Gallbladder Cancer Incidence And Mortality United States 1999-2011 Background: Gallbladder cancer is a rare cancer with unusual distribution, and few population-based estimates for the United States have been published. \n\n Methods: Using population-based cancer incidence and mortality data, we examined U.S. gallbladder cancer incidence and death rates for 2007-2011 and trends for 1999-2011. \n\n Results: During 2007 to 2011, approximately 3,700 persons were diagnosed with primary gallbladder cancer (rate = 1.13 cases per 100,000) and 2,000 died from the disease (rate = 0.62 deaths per 100,000) each year in the United States. Two thirds of gallbladder cancer cases and deaths occurred among women. Gallbladder cancer incidence and death rates were three times higher among American Indian and Alaska Native persons than non-Hispanic white persons. By state, gallbladder cancer incidence and death rates ranged by about 2-fold. During 1999 to 2011, gallbladder cancer incidence rates decreased among women but remained level among men; death rates declined among women but stabilized among men after declining from 1999 to 2006. Gallbladder cancer incidence rates increased in some subgroups, notably among black persons, those aged <45 years, and for endocrine tumors. \n\n Conclusions: Data from U.S. population-based cancer registries confirm that gallbladder cancer incidence and death rates are higher among women than men, highest among American Indian and Alaska Native persons, and differ by region. While overall incidence and death rates decreased during 1999 to 2011, incidence rates increased among some small subgroups. \n\n Impact: Surveillance of gallbladder cancer incidence and mortality, particularly to monitor increases in subgroups, may provide clues to etiology and stimulate further research. STN","prediction_labels":"HUMAN"},{"cleaned":"impact adjuvant chemotherapy regimen survival outcomes immunohistochemical subtypes ampullary carcinoma background objectives ampullary adenocarcinoma aa classified immunohistochemical ihc subtypes intestinal pancreatobiliary pb ambiguous impact adjuvant therapy ihc subtype disease stage unclear examined effect adjuvant chemotherapy regimen survival ampullary cancers ihc subtype disease stage methods review pancreatoduodenectomy pd performed aa 2005 2013 single center impact regimen ihc subtype stage analyzed results one hundred twenty one patients subtyped 32 pb 48 20 overall survival 45 6 31 3 46 9 months respectively pb higher pathologic stage positive lymph node disease perineural lymphovascular invasion p 05 5 fluorouracil fu based adjuvant therapy improved survival compared treatment 87 4 vs 32 1 months p 046 receipt 5 fu emerged independent predictor improved survival hazard ratio hr 0 244 p 031 regardless subtype 5 fu superior gemcitabine advanced stage disease stage iib iii vs iia hr 0 35 p 05 conclusions adjuvant therapy 5 fu confers survival benefit patients advanced stage aa regardless subtype impact various chemotherapy regimens subtypes ampullary cancer warrants investigation stn","probabilities":0.9799733,"Title":"Impact Of Adjuvant Chemotherapy Regimen On Survival Outcomes In Immunohistochemical Subtypes Of Ampullary Carcinoma","Abstract":"Background and objectives: Ampullary adenocarcinoma (AA) is classified by immunohistochemical (IHC) subtypes into intestinal (IN), pancreatobiliary (PB), and ambiguous (AM). The impact of adjuvant therapy on IHC subtype and disease stage is unclear. We examined the effect of adjuvant chemotherapy regimen on survival of ampullary cancers by IHC subtype and disease stage. \r\n\r\n Methods: Review of pancreatoduodenectomy (PD) performed for AA between 2005 and 2013 at a single center. The impact of regimen on IHC subtype and stage was analyzed. \r\n\r\n Results: One hundred and twenty-one patients were subtyped: IN = 32%, PB = 48%, and AM = 20% with overall survival of 45.6, 31.3, and 46.9 months, respectively. PB had higher pathologic T-stage, positive lymph node disease, and perineural and lymphovascular invasion (P < .05). 5-Fluorouracil (FU)-based adjuvant therapy improved survival compared to no treatment (87.4 vs 32.1 months; P = .046), and receipt of 5-FU emerged as an independent predictor of improved survival (hazard ratio [HR] 0.244; P = .031) regardless of subtype. 5-FU was superior to Gemcitabine in advanced-stage disease (stage IIB and III vs I+IIA, HR: 0.35; P < .05). \r\n\r\n Conclusions: Adjuvant therapy with 5-FU confers a survival benefit in patients with advanced-stage AA regardless of subtype. The impact of various chemotherapy regimens on subtypes of ampullary cancer warrants further investigation.","Source":"STN","category":"HUMAN","training_data":"Impact Of Adjuvant Chemotherapy Regimen On Survival Outcomes In Immunohistochemical Subtypes Of Ampullary Carcinoma Background and objectives: Ampullary adenocarcinoma (AA) is classified by immunohistochemical (IHC) subtypes into intestinal (IN), pancreatobiliary (PB), and ambiguous (AM). The impact of adjuvant therapy on IHC subtype and disease stage is unclear. We examined the effect of adjuvant chemotherapy regimen on survival of ampullary cancers by IHC subtype and disease stage. \r\n\r\n Methods: Review of pancreatoduodenectomy (PD) performed for AA between 2005 and 2013 at a single center. The impact of regimen on IHC subtype and stage was analyzed. \r\n\r\n Results: One hundred and twenty-one patients were subtyped: IN = 32%, PB = 48%, and AM = 20% with overall survival of 45.6, 31.3, and 46.9 months, respectively. PB had higher pathologic T-stage, positive lymph node disease, and perineural and lymphovascular invasion (P < .05). 5-Fluorouracil (FU)-based adjuvant therapy improved survival compared to no treatment (87.4 vs 32.1 months; P = .046), and receipt of 5-FU emerged as an independent predictor of improved survival (hazard ratio [HR] 0.244; P = .031) regardless of subtype. 5-FU was superior to Gemcitabine in advanced-stage disease (stage IIB and III vs I+IIA, HR: 0.35; P < .05). \r\n\r\n Conclusions: Adjuvant therapy with 5-FU confers a survival benefit in patients with advanced-stage AA regardless of subtype. The impact of various chemotherapy regimens on subtypes of ampullary cancer warrants further investigation. STN","prediction_labels":"HUMAN"},{"cleaned":"recent developments research biomarkers cholangiocarcinoma primary sclerosing cholangitis primary sclerosing cholangitis psc characterized chronic inflammatory process bile ducts unclear aetiology often complicated cholangiocarcinoma cca dismal prognosis early detection cca important treatment options advanced disease limited besides established markers like ca19 9 recent developments made using latest technologies review summarizes recent advances remaining limitations biomarkers cca psc pubmed","probabilities":0.9799733,"Title":"Recent developments in the research on biomarkers of cholangiocarcinoma in primary sclerosing cholangitis","Abstract":"Primary sclerosing cholangitis (PSC) is characterized by a chronic inflammatory process of the bile ducts of unclear aetiology. It is often complicated by cholangiocarcinoma (CCA) with a dismal prognosis. Early detection of CCA is important because treatment options for advanced disease are limited. Besides the established markers, like CA19-9, recent developments have been made using latest technologies. This review summarizes the recent advances and remaining limitations of biomarkers of CCA in PSC.","Source":"PubMed","category":"HUMAN","training_data":"Recent developments in the research on biomarkers of cholangiocarcinoma in primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is characterized by a chronic inflammatory process of the bile ducts of unclear aetiology. It is often complicated by cholangiocarcinoma (CCA) with a dismal prognosis. Early detection of CCA is important because treatment options for advanced disease are limited. Besides the established markers, like CA19-9, recent developments have been made using latest technologies. This review summarizes the recent advances and remaining limitations of biomarkers of CCA in PSC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"combination conservative interventional therapy strategies intra extrahepatic cholangiocellular carcinoma retrospective survival analysis background due predominantly advanced stage time diagnosis treatment cholangiocarcinoma difficult apart surgical resection interventional treatment strategies increasingly used advanced stage tumours aim study retrospective comparison effect various forms treatment morbidity mortality method total 195 patients received either chemotherapy combination photodynamic therapy pdt transarterial chemoembolization tace chemotherapy results median survival rate patients 15 6 months 50 8 still alive 1 year diagnosis patients previously undergone surgery survived 17 1 months longer without surgical treatment p 01 chemotherapy prolonged survival 9 2 months p 47 palliative patients combination chemotherapy pdt survived average 1 8 months longer p 28 chemotherapy tace 9 8 months longer p 04 compared chemotherapy alone conclusions appears surgical treatment chemotherapy combined pdt tace may prolong survival stn","probabilities":0.9799733,"Title":"Combination Of Conservative And Interventional Therapy Strategies For Intra- And Extrahepatic Cholangiocellular Carcinoma: A Retrospective Survival Analysis","Abstract":"Background. Due to the predominantly advanced stage at the time of diagnosis treatment of cholangiocarcinoma is difficult. Apart from surgical resection, interventional treatment strategies are increasingly used in advanced stage tumours. The aim of the study was a retrospective comparison of the effect of the various forms of treatment on morbidity and mortality. Method. A total of 195 patients, received either chemotherapy or a combination of photodynamic therapy (PDT) or transarterial chemoembolization (TACE) and chemotherapy. Results. The median survival rate for all patients was 15.6 months, 50.8% were still alive 1 year after diagnosis. Patients, who had previously undergone surgery, survived 17.1 months longer than those without surgical treatment (P < .01). Chemotherapy prolonged the survival by 9.2 months (P = .47). Palliative patients under combination of chemotherapy and PDT survived on average 1.8 months longer (P = .28), with chemotherapy and TACE 9.8 months longer (P = .04) compared to chemotherapy alone. Conclusions. It appears that surgical treatment and chemotherapy combined with PDT or TACE may prolong survival.","Source":"STN","category":"HUMAN","training_data":"Combination Of Conservative And Interventional Therapy Strategies For Intra- And Extrahepatic Cholangiocellular Carcinoma: A Retrospective Survival Analysis Background. Due to the predominantly advanced stage at the time of diagnosis treatment of cholangiocarcinoma is difficult. Apart from surgical resection, interventional treatment strategies are increasingly used in advanced stage tumours. The aim of the study was a retrospective comparison of the effect of the various forms of treatment on morbidity and mortality. Method. A total of 195 patients, received either chemotherapy or a combination of photodynamic therapy (PDT) or transarterial chemoembolization (TACE) and chemotherapy. Results. The median survival rate for all patients was 15.6 months, 50.8% were still alive 1 year after diagnosis. Patients, who had previously undergone surgery, survived 17.1 months longer than those without surgical treatment (P < .01). Chemotherapy prolonged the survival by 9.2 months (P = .47). Palliative patients under combination of chemotherapy and PDT survived on average 1.8 months longer (P = .28), with chemotherapy and TACE 9.8 months longer (P = .04) compared to chemotherapy alone. Conclusions. It appears that surgical treatment and chemotherapy combined with PDT or TACE may prolong survival. STN","prediction_labels":"HUMAN"},{"cleaned":"raddeanin promotes apoptosis ameliorates 5 fluorouracil resistance cholangiocarcinoma cells background bile duct cancer characterized fast metastasis invasion regarded one aggressive tumors due absence effective diagnosis early stage therefore urgent demand explore novel diagnostic approaches therapeutic strategies bile duct cancer improve patient survival raddeanin ra extracted anemone raddeana regel demonstrated play antitumor roles various cancers aim investigate effects ra treatment bile duct cancer cells methods study four cholangiocarcinoma cell lines rbe lipf155c lipf178c liccf treated ra used test cell viability ra associated cell functional analysis 5 fluorouracil 5 fu effectiveness well cell cycle apoptosis related protein expression investigated results ra reduced cell viability dose dependent pattern four cell lines migration colony formation abilities also impaired ra rbe lipf155c cell lines ra sensitized cell lines 5 fu treatment enhanced effects 5 fu cholangiocarcinoma also ra decreased protein expression wee1 combinational effect ra 5 fu decreased protein expressions cyclooxygenase 2 b cell lymphoma 2 wee1 increased protein levels bax cyclin d1 cyclin e conclusion taken together results suggest ra acts anti cancer agent enhancer 5 fu bile duct cancer cells via regulating multiple cell cycle apoptosis related proteins finding provides novel clues exploring novel antitumor drug bile duct cancer stn","probabilities":0.9467213,"Title":"Raddeanin A Promotes Apoptosis And Ameliorates 5-Fluorouracil Resistance In Cholangiocarcinoma Cells","Abstract":"Background: Bile duct cancer is characterized by fast metastasis and invasion and has been regarded as one of the most aggressive tumors due to the absence of effective diagnosis at an early stage. Therefore, it is in the urgent demand to explore novel diagnostic approaches and therapeutic strategies for bile duct cancer to improve patient survival. Raddeanin A (RA) is extracted from the anemone raddeana regel and has been demonstrated to play antitumor roles in various cancers. \r\n\r\n Aim: To investigate the effects of RA treatment on bile duct cancer cells. \r\n\r\n Methods: In this study, four cholangiocarcinoma cell lines (RBE, LIPF155C, LIPF178C, and LICCF) treated with RA were used to test the cell viability. The RA-associated cell functional analysis, 5-fluorouracil (5-Fu) effectiveness as well as cell cycle- and apoptosis-related protein expression were investigated. \r\n\r\n Results: RA reduced cell viability in a dose-dependent pattern in four cell lines, and the migration and colony formation abilities were also impaired by RA in RBE and LIPF155C cell lines. RA sensitized cell lines to 5-Fu treatment and enhanced the effects of 5-Fu in cholangiocarcinoma. Also, RA decreased protein expression of Wee1, while the combinational effect of RA and 5-Fu decreased protein expressions of cyclooxygenase-2, B cell lymphoma 2, and Wee1 but increased protein levels of Bax, cyclin D1, and cyclin E. \r\n\r\n Conclusion: Taken together, the results suggest that RA acts as an anti-cancer agent and enhancer of 5-Fu in bile duct cancer cells via regulating multiple cell cycle and apoptosis-related proteins. This finding provides novel clues to exploring a novel antitumor drug for bile duct cancer.","Source":"STN","category":"ANIMAL","training_data":"Raddeanin A Promotes Apoptosis And Ameliorates 5-Fluorouracil Resistance In Cholangiocarcinoma Cells Background: Bile duct cancer is characterized by fast metastasis and invasion and has been regarded as one of the most aggressive tumors due to the absence of effective diagnosis at an early stage. Therefore, it is in the urgent demand to explore novel diagnostic approaches and therapeutic strategies for bile duct cancer to improve patient survival. Raddeanin A (RA) is extracted from the anemone raddeana regel and has been demonstrated to play antitumor roles in various cancers. \r\n\r\n Aim: To investigate the effects of RA treatment on bile duct cancer cells. \r\n\r\n Methods: In this study, four cholangiocarcinoma cell lines (RBE, LIPF155C, LIPF178C, and LICCF) treated with RA were used to test the cell viability. The RA-associated cell functional analysis, 5-fluorouracil (5-Fu) effectiveness as well as cell cycle- and apoptosis-related protein expression were investigated. \r\n\r\n Results: RA reduced cell viability in a dose-dependent pattern in four cell lines, and the migration and colony formation abilities were also impaired by RA in RBE and LIPF155C cell lines. RA sensitized cell lines to 5-Fu treatment and enhanced the effects of 5-Fu in cholangiocarcinoma. Also, RA decreased protein expression of Wee1, while the combinational effect of RA and 5-Fu decreased protein expressions of cyclooxygenase-2, B cell lymphoma 2, and Wee1 but increased protein levels of Bax, cyclin D1, and cyclin E. \r\n\r\n Conclusion: Taken together, the results suggest that RA acts as an anti-cancer agent and enhancer of 5-Fu in bile duct cancer cells via regulating multiple cell cycle and apoptosis-related proteins. This finding provides novel clues to exploring a novel antitumor drug for bile duct cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"sex differences opisthorchiosis development cholangiocarcinoma syrian hamster model worldwide highest incidence cholangiocarcinoma cca found northeast thailand endemic area opisthorchis viverrini infection cumulated clinical data revealed majority cca patients men however many types cancers commonly found women study investigated sex differences development cca induced o viverrini infection n nitrosodimethylamine administration syrian hamsters histopathology liver function tests fecal egg counts analyzed results showed sex differences hamsters responses o viverrini infection prevalence cca development even though serum alt level o viverrini infected cca hamsters significantly increased female compared male p 0 05 uninfected control p 0 05 results may imply higher prevalence opisthorchiasis cca men women northeast thailand may depend behaviors individual exposed risk factors rather gender difference stn","probabilities":0.9799733,"Title":"Sex Differences In Opisthorchiosis And The Development Of Cholangiocarcinoma In Syrian Hamster Model","Abstract":"Worldwide, the highest incidence of cholangiocarcinoma (CCA) is found in northeast Thailand, the endemic area of Opisthorchis viverrini infection. Cumulated clinical data revealed that the majority of CCA patients are men. However, many other types of cancers are more commonly found in women. In this study, we investigated the sex differences in the development of CCA, induced by O. viverrini infection and N-nitrosodimethylamine administration, in Syrian hamsters. Histopathology, liver function tests, and fecal egg counts were analyzed. The results showed that there are no sex differences in hamsters responses to O. viverrini infection and no prevalence of CCA development. Even though serum ALT level in O. viverrini-infected or CCA hamsters was significantly increased in female compared to male (p < 0.05) and uninfected control (p < 0.05), our results may imply that the higher prevalence of opisthorchiasis and CCA in men than in women in northeast Thailand may depend on behaviors of an individual exposed to risk factors rather than gender difference.","Source":"STN","category":"ANIMAL","training_data":"Sex Differences In Opisthorchiosis And The Development Of Cholangiocarcinoma In Syrian Hamster Model Worldwide, the highest incidence of cholangiocarcinoma (CCA) is found in northeast Thailand, the endemic area of Opisthorchis viverrini infection. Cumulated clinical data revealed that the majority of CCA patients are men. However, many other types of cancers are more commonly found in women. In this study, we investigated the sex differences in the development of CCA, induced by O. viverrini infection and N-nitrosodimethylamine administration, in Syrian hamsters. Histopathology, liver function tests, and fecal egg counts were analyzed. The results showed that there are no sex differences in hamsters responses to O. viverrini infection and no prevalence of CCA development. Even though serum ALT level in O. viverrini-infected or CCA hamsters was significantly increased in female compared to male (p < 0.05) and uninfected control (p < 0.05), our results may imply that the higher prevalence of opisthorchiasis and CCA in men than in women in northeast Thailand may depend on behaviors of an individual exposed to risk factors rather than gender difference. STN","prediction_labels":"HUMAN"},{"cleaned":"advances biomarkers biliary tract cancers tumor biomarkers applied early diagnosis precise treatment thereby leading personalized treatment better outcomes biliary tract cancers btcs group cancers occurs different locations different clinical genetic properties though incidence btcs rare btcs among lethal cancers world low 5 year survivals lack efficient early diagnostic approaches adjuvant therapies btcs main reasons urge us broaden researches btc biomarkers although progresses diagnostic biomarkers btcs achieved still advances prognostic predictive therapeutic areas review focus achievements pubmed","probabilities":0.9799733,"Title":"Advances in biomarkers of biliary tract cancers","Abstract":"Tumor biomarkers can be applied for early diagnosis or precise treatment, thereby leading to personalized treatment and better outcomes. Biliary tract cancers (BTCs) are a group of cancers that occurs in different locations and have different clinical or genetic properties. Though the incidence of BTCs is rare, BTCs are among the most lethal cancers in the world and all have very low 5-year survivals. Lack of efficient early diagnostic approaches or adjuvant therapies for BTCs are main reasons. These urge us to broaden the researches into BTC biomarkers. Although few progresses of diagnostic biomarkers for BTCs have been achieved, there are still some advances in prognostic, predictive and therapeutic areas. In this review, we will focus on these achievements.","Source":"PubMed","category":"HUMAN","training_data":"Advances in biomarkers of biliary tract cancers Tumor biomarkers can be applied for early diagnosis or precise treatment, thereby leading to personalized treatment and better outcomes. Biliary tract cancers (BTCs) are a group of cancers that occurs in different locations and have different clinical or genetic properties. Though the incidence of BTCs is rare, BTCs are among the most lethal cancers in the world and all have very low 5-year survivals. Lack of efficient early diagnostic approaches or adjuvant therapies for BTCs are main reasons. These urge us to broaden the researches into BTC biomarkers. Although few progresses of diagnostic biomarkers for BTCs have been achieved, there are still some advances in prognostic, predictive and therapeutic areas. In this review, we will focus on these achievements. PubMed","prediction_labels":"HUMAN"},{"cleaned":"mass forming intrahepatic cholangiocarcinoma diffusion weighted imaging preoperative prognostic marker purpose assess value diffusion weighted dw imaging prognostic marker preoperative evaluation patients mass forming intrahepatic cholangiocarcinoma icc materials methods retrospective study approved institutional review board informed consent requirement waived total 91 patients underwent hepatic resection dw imaging mass forming icc included two radiologists evaluated degree diffusion restriction tumors using qualitative visual interpretation combined quantitative analysis volumetric evaluation whole tumor dw images patients classified two groups less one third tumor showed diffusion restriction group 1 one third tumor showed diffusion restriction group 2 imaging findings tumors compared pathology findings disease free overall survival rates compared two groups using kaplan meier method log rank test results 43 patients group 1 48 patients group 2 1 3 year disease free survival rates 30 16 respectively group 1 75 64 respectively group 2 p 001 1 3 year overall survival rates 77 26 respectively group 1 92 67 respectively group 2 p 001 multivariate analysis revealed diffusion restriction p 024 differentiation p 030 intrahepatic metastasis p 001 independent prognostic factors overall survival conclusion degree diffusion restriction dw images may prognostic marker preoperative evaluation patients mass forming icc rsna 2016 online supplemental material available article pubmed","probabilities":0.9799733,"Title":"Mass-forming Intrahepatic Cholangiocarcinoma: Diffusion-weighted Imaging as a Preoperative Prognostic Marker","Abstract":"Purpose To assess the value of diffusion-weighted (DW) imaging as a prognostic marker in preoperative evaluation of patients with mass-forming intrahepatic cholangiocarcinoma (ICC). Materials and Methods This retrospective study was approved by the institutional review board, and the informed consent requirement was waived. A total of 91 patients who underwent hepatic resection and DW imaging for mass-forming ICC were included. Two radiologists evaluated the degree of diffusion restriction of the tumors by using qualitative (visual) interpretation combined with quantitative analysis by volumetric evaluation of the whole tumor on DW images. Patients were classified into two groups: those in whom less than one-third of the tumor showed diffusion restriction (group 1) and those in whom more than one-third of the tumor showed diffusion restriction (group 2). Imaging findings in tumors were compared with pathology findings. Disease-free and overall survival rates were compared between the two groups by using the Kaplan-Meier method with the log-rank test. Results There were 43 patients in group 1 and 48 patients in group 2. The 1- and 3-year disease-free survival rates were 30% and 16%, respectively, in group 1 and 75% and 64%, respectively, in group 2 (P < .001). The 1- and 3-year overall survival rates were 77% and 26%, respectively, in group 1 and 92% and 67%, respectively, in group 2 (P = .001). Multivariate analysis revealed that diffusion restriction (P = .024), differentiation (P = .030), and intrahepatic metastasis (P = .001) were independent prognostic factors for overall survival. Conclusion The degree of diffusion restriction on DW images may be a prognostic marker in preoperative evaluation of patients with mass-forming ICC. (©) RSNA, 2016 Online supplemental material is available for this article.","Source":"PubMed","category":"HUMAN","training_data":"Mass-forming Intrahepatic Cholangiocarcinoma: Diffusion-weighted Imaging as a Preoperative Prognostic Marker Purpose To assess the value of diffusion-weighted (DW) imaging as a prognostic marker in preoperative evaluation of patients with mass-forming intrahepatic cholangiocarcinoma (ICC). Materials and Methods This retrospective study was approved by the institutional review board, and the informed consent requirement was waived. A total of 91 patients who underwent hepatic resection and DW imaging for mass-forming ICC were included. Two radiologists evaluated the degree of diffusion restriction of the tumors by using qualitative (visual) interpretation combined with quantitative analysis by volumetric evaluation of the whole tumor on DW images. Patients were classified into two groups: those in whom less than one-third of the tumor showed diffusion restriction (group 1) and those in whom more than one-third of the tumor showed diffusion restriction (group 2). Imaging findings in tumors were compared with pathology findings. Disease-free and overall survival rates were compared between the two groups by using the Kaplan-Meier method with the log-rank test. Results There were 43 patients in group 1 and 48 patients in group 2. The 1- and 3-year disease-free survival rates were 30% and 16%, respectively, in group 1 and 75% and 64%, respectively, in group 2 (P < .001). The 1- and 3-year overall survival rates were 77% and 26%, respectively, in group 1 and 92% and 67%, respectively, in group 2 (P = .001). Multivariate analysis revealed that diffusion restriction (P = .024), differentiation (P = .030), and intrahepatic metastasis (P = .001) were independent prognostic factors for overall survival. Conclusion The degree of diffusion restriction on DW images may be a prognostic marker in preoperative evaluation of patients with mass-forming ICC. (©) RSNA, 2016 Online supplemental material is available for this article. PubMed","prediction_labels":"HUMAN"},{"cleaned":"antitumor effect novel sphingosine kinase 2 inhibitor abc294640 enhanced inhibition autophagy sorafenib human cholangiocarcinoma cells sphingosine kinase 2 sphk2 oncogenic role cancer recently developed first class sphk2 specific inhibitor abc294640 displays antitumor activity many cancer models however role sphk2 antitumor activity inhibitor abc294640 known cholangiocarcinoma investigated potential targeting sphk2 treatment cholangiocarcinoma found sphk2 overexpressed five established human cholangiocarcinoma cell lines witt hucct1 egi 1 oz huh28 new patient derived cholangiocarcinoma cell line liv27 compared h69 normal cholangiocytes inhibition sphk2 abc294640 inhibited proliferation induced caspase dependent apoptosis furthermore found abc294640 inhibited stat3 phosphorylation one key signaling pathways regulating cholangiocarcinoma cell proliferation survival abc294640 also induced autophagy inhibition autophagy bafilomycin a1 chloroquine potentiated abc294640 induced cytotoxicity apoptosis addition abc294640 combination sorafenib synergistically inhibited cell proliferation cholangiocarcinoma cells strong decreases stat3 phosphorylation observed witt hucct1 cells exposed abc294640 sorafenib combination findings provide novel evidence sphk2 may rational therapeutic target cholangiocarcinoma combinations abc294640 sorafenib autophagy inhibitors may provide novel strategies treatment cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Antitumor Effect Of The Novel Sphingosine Kinase 2 Inhibitor Abc294640 Is Enhanced By Inhibition Of Autophagy And By Sorafenib In Human Cholangiocarcinoma Cells","Abstract":"Sphingosine kinase 2 (Sphk2) has an oncogenic role in cancer. A recently developed first-in-class Sphk2 specific inhibitor ABC294640 displays antitumor activity in many cancer models. However, the role of Sphk2 and the antitumor activity of its inhibitor ABC294640 are not known in cholangiocarcinoma. We investigated the potential of targeting Sphk2 for the treatment of cholangiocarcinoma. We found that Sphk2 is overexpressed in five established human cholangiocarcinoma cell lines (WITT, HuCCT1, EGI-1, OZ and HuH28) and a new patient-derived cholangiocarcinoma cell line (LIV27) compared to H69 normal cholangiocytes. Inhibition of Sphk2 by ABC294640 inhibited proliferation and induced caspase-dependent apoptosis. Furthermore, we found that ABC294640 inhibited STAT3 phosphorylation, one of the key signaling pathways regulating cholangiocarcinoma cell proliferation and survival. ABC294640 also induced autophagy. Inhibition of autophagy by bafilomycin A1 or chloroquine potentiated ABC294640-induced cytotoxicity and apoptosis. In addition, ABC294640 in combination with sorafenib synergistically inhibited cell proliferation of cholangiocarcinoma cells. Strong decreases in STAT3 phosphorylation were observed in WITT and HuCCT1 cells exposed to the ABC294640 and sorafenib combination. These findings provide novel evidence that Sphk2 may be a rational therapeutic target in cholangiocarcinoma. Combinations of ABC294640 with sorafenib and/or autophagy inhibitors may provide novel strategies for the treatment of cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Antitumor Effect Of The Novel Sphingosine Kinase 2 Inhibitor Abc294640 Is Enhanced By Inhibition Of Autophagy And By Sorafenib In Human Cholangiocarcinoma Cells Sphingosine kinase 2 (Sphk2) has an oncogenic role in cancer. A recently developed first-in-class Sphk2 specific inhibitor ABC294640 displays antitumor activity in many cancer models. However, the role of Sphk2 and the antitumor activity of its inhibitor ABC294640 are not known in cholangiocarcinoma. We investigated the potential of targeting Sphk2 for the treatment of cholangiocarcinoma. We found that Sphk2 is overexpressed in five established human cholangiocarcinoma cell lines (WITT, HuCCT1, EGI-1, OZ and HuH28) and a new patient-derived cholangiocarcinoma cell line (LIV27) compared to H69 normal cholangiocytes. Inhibition of Sphk2 by ABC294640 inhibited proliferation and induced caspase-dependent apoptosis. Furthermore, we found that ABC294640 inhibited STAT3 phosphorylation, one of the key signaling pathways regulating cholangiocarcinoma cell proliferation and survival. ABC294640 also induced autophagy. Inhibition of autophagy by bafilomycin A1 or chloroquine potentiated ABC294640-induced cytotoxicity and apoptosis. In addition, ABC294640 in combination with sorafenib synergistically inhibited cell proliferation of cholangiocarcinoma cells. Strong decreases in STAT3 phosphorylation were observed in WITT and HuCCT1 cells exposed to the ABC294640 and sorafenib combination. These findings provide novel evidence that Sphk2 may be a rational therapeutic target in cholangiocarcinoma. Combinations of ABC294640 with sorafenib and/or autophagy inhibitors may provide novel strategies for the treatment of cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"cancer incidence mortality firefighters state art review meta analysis objective systematic literature review meta analysis conducted association firefighting cancer methods comprehensive literature search databases including medline embase biosis nioshtic2 web science cancerlit healthstar period 1966 january 2007 conducted also retrieved additional studies manual searching results total 49 studies included meta analysis found statistically significant associations firefighting cancers bladder brain cns colorectal cancers consistent several previous risk estimates also found statistically significant associations firefighting non hodgkin lymphoma skin melanoma prostate testicular cancer kidney hodgkin lymphoma leukemia lymphosarcoma reticulosarcoma multiple myeloma pancreatic cancer found statistically significant less consistent results cancers evaluated esophageal laryngeal oral pharyngeal liver gallbladder lung lymphatic hematopoietic non melanoma skin cancer stomach urinary cancer find statistically significant associations conclusions although meta analysis showed statistically significant increased risks either cancer incidence mortality certain cancers association firefighting number important limitations underlying studies exist precluded ability arrive definitive conclusions regarding causation pubmed","probabilities":0.9799733,"Title":"Cancer Incidence and Mortality in Firefighters: A State-of-the-Art Review and Meta-َAnalysis","Abstract":"OBJECTIVE: A systematic literature review and meta-analysis was conducted on the association between firefighting and cancer. METHODS: A comprehensive literature search of databases including Medline, EMBASE, Biosis, NIOSHTIC2, Web of Science, Cancerlit, and HealthStar, for the period between 1966 to January 2007, was conducted. We also retrieved additional studies by manual searching. RESULTS: A total of 49 studies were included in the meta-analysis. We found statistically significant associations between firefighting and cancers of bladder, brain and CNS, and colorectal cancers, consistent with several previous risk estimates. We also found statistically significant associations of firefighting with non-Hodgkin's lymphoma, skin melanoma, prostate, and testicular cancer. For kidney, Hodgkin's lymphoma, leukemia, lymphosarcoma and reticulosarcoma, multiple myeloma, and pancreatic cancer, we found some statistically significant but less consistent results. For all other cancers evaluated (esophageal, laryngeal, oral and pharyngeal, liver and gallbladder, lung, lymphatic and hematopoietic, non-melanoma skin cancer, stomach, and urinary cancer) we did not find any statistically significant associations. CONCLUSIONS: Although our meta-analysis showed statistically significant increased risks of either cancer incidence or mortality of certain cancers in association with firefighting, a number of important limitations of the underlying studies exist, which, precluded our ability to arrive at definitive conclusions regarding causation.","Source":"PubMed","category":"HUMAN","training_data":"Cancer Incidence and Mortality in Firefighters: A State-of-the-Art Review and Meta-َAnalysis OBJECTIVE: A systematic literature review and meta-analysis was conducted on the association between firefighting and cancer. METHODS: A comprehensive literature search of databases including Medline, EMBASE, Biosis, NIOSHTIC2, Web of Science, Cancerlit, and HealthStar, for the period between 1966 to January 2007, was conducted. We also retrieved additional studies by manual searching. RESULTS: A total of 49 studies were included in the meta-analysis. We found statistically significant associations between firefighting and cancers of bladder, brain and CNS, and colorectal cancers, consistent with several previous risk estimates. We also found statistically significant associations of firefighting with non-Hodgkin's lymphoma, skin melanoma, prostate, and testicular cancer. For kidney, Hodgkin's lymphoma, leukemia, lymphosarcoma and reticulosarcoma, multiple myeloma, and pancreatic cancer, we found some statistically significant but less consistent results. For all other cancers evaluated (esophageal, laryngeal, oral and pharyngeal, liver and gallbladder, lung, lymphatic and hematopoietic, non-melanoma skin cancer, stomach, and urinary cancer) we did not find any statistically significant associations. CONCLUSIONS: Although our meta-analysis showed statistically significant increased risks of either cancer incidence or mortality of certain cancers in association with firefighting, a number of important limitations of the underlying studies exist, which, precluded our ability to arrive at definitive conclusions regarding causation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact immunohistochemical expression ck7 ck20 curatively resected ampulla vater cancer background consideration ampullary adenocarcinoma stage lymph node metastases perineural invasion tumor differentiation pancraticobiliary type lymph node ratio considered prognostic factors objectives study investigate surgical outcomes clinicopathological predictors affecting survival recurrence examine prognostic roles histopathological subtype immunohistochemical markers methods april 2006 september 2012 37 patients underwent curative resection ampullar vater adenocarcinoma enrolled study retrospective review performed based medical records immunohistochemical expression histopathological type clinicopathologic factors analyzed results 5 year overall survival rates disease free survival rates surgery 77 4 75 7 respectively multivariate cox regression analysis showed advanced stage p 0 019 positive expression cytokeratin 7 ck7 negative expression cytokeratin 20 ck20 p 0 046 identified significant independent factors related survival poor differentiation p 0 031 significantly influenced disease free survival multivariate analysis conclusions advanced stage significant prognostic factor affecting survival ampullary adenocarcinoma also positive expression ck7 negative expression ck20 independent factor related overall survival pubmed","probabilities":0.9799733,"Title":"Prognostic impact of immunohistochemical expression of CK7 and CK20 in curatively resected ampulla of Vater cancer","Abstract":"BACKGROUND: In the consideration of ampullary adenocarcinoma, T stage, lymph node metastases, perineural invasion, tumor differentiation, pancraticobiliary type, and lymph node ratio are considered prognostic factors. The objectives of this study were to investigate surgical outcomes and the clinicopathological predictors affecting survival and recurrence, and to examine the prognostic roles of histopathological subtype and immunohistochemical markers. METHODS: From April 2006 to September 2012, 37 patients who underwent curative resection of ampullar of Vater adenocarcinoma were enrolled in this study. A retrospective review was performed based on medical records. Immunohistochemical expression, histopathological type and clinicopathologic factors were analyzed. RESULTS: The 5-year overall survival rates and disease-free survival rates after surgery were 77.4 and 75.7 %, respectively. Multivariate Cox regression analysis showed that advanced T stage (p = 0.019) and positive expression of Cytokeratin 7 (CK7) with negative expression of Cytokeratin 20 (CK20) (p = 0.046) were identified as significant independent factors related to survival, and poor differentiation (p = 0.031) significantly influenced disease-free survival in multivariate analysis. CONCLUSIONS: Advanced T stage is a significant prognostic factor affecting survival in ampullary adenocarcinoma. Also, positive expression of CK7 with negative expression of CK20 is an independent factor related to overall survival.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic impact of immunohistochemical expression of CK7 and CK20 in curatively resected ampulla of Vater cancer BACKGROUND: In the consideration of ampullary adenocarcinoma, T stage, lymph node metastases, perineural invasion, tumor differentiation, pancraticobiliary type, and lymph node ratio are considered prognostic factors. The objectives of this study were to investigate surgical outcomes and the clinicopathological predictors affecting survival and recurrence, and to examine the prognostic roles of histopathological subtype and immunohistochemical markers. METHODS: From April 2006 to September 2012, 37 patients who underwent curative resection of ampullar of Vater adenocarcinoma were enrolled in this study. A retrospective review was performed based on medical records. Immunohistochemical expression, histopathological type and clinicopathologic factors were analyzed. RESULTS: The 5-year overall survival rates and disease-free survival rates after surgery were 77.4 and 75.7 %, respectively. Multivariate Cox regression analysis showed that advanced T stage (p = 0.019) and positive expression of Cytokeratin 7 (CK7) with negative expression of Cytokeratin 20 (CK20) (p = 0.046) were identified as significant independent factors related to survival, and poor differentiation (p = 0.031) significantly influenced disease-free survival in multivariate analysis. CONCLUSIONS: Advanced T stage is a significant prognostic factor affecting survival in ampullary adenocarcinoma. Also, positive expression of CK7 with negative expression of CK20 is an independent factor related to overall survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"novel immune inflammatory score predict survival patients pts advanced biliary tract cancer abtc receiving first line chemotherapy 1 line cht background cht isthe mainstay treatment abtc median overall survival mos 12 months given palliative intent treatment itslimited survival gain notnegligible toxicities itis paramount importance properly select pts determinantsof immune inflammation regarded aspromising prognostic factors abtc methods clinical laboratory data starting1 line cht evaluated 123 ptswith unresectable locally advancedand metastatic abtc intrahepatic perihilar distal cholangiocarcinoma gallbladder cancer treated 1st january 2010 31st july 2017 modena cancer centre potential prognostic factors assessed univariate cox proportional hazardunivariate model multivariate analyses multiple cox proportional hazard regression likelihood ratio test results univariate analysis ecog ps 0 metastatic disease gallbladder cancer previous surgery monocht ldh upper limit normal albumine 3 5gr dl absoluteneutrophilcount anc 8000 ml lymphocyte monocyteratio lmr 2 1 neutrophil lymphocyte ratio nlr 3 platelet lymphocyte ratio 160 ast 40iu l gamma glutamyl transpeptidase 40iu l cea 9 5ng ml ca19 9 700u lwere significantly associate shorter os multivariate analysis lmr 2 1 nlr 3 anc 8000 ml albumine 3 5gr dl retained statistical significance poor prognostic factors combining four variables three different risk groups identified low risk group 0 factors intermediate risk group 1 2factors high risk group 3 4 factors mos 22 12 5monthsrespectively p 0 001 prognostic value score indipendentfrom treatment procedures doubletvs monocht primary tumour site p 0 001 conclusions developed cost effective easily available scoring system discriminates abtc treated 1 line cht three different statistically significant prognostic groups itcould become ausefultool toadd established factors improving pts selectionin dailypractice google scholar","probabilities":0.9799733,"Title":"A Novel Immune-Inflammatory Score To Predict Survival In Patients (Pts) With Advanced Biliary Tract Cancer (Abtc) Receiving First-Line Chemotherapy (1-Line Cht)","Abstract":"Background: Cht isthe mainstay of treatment for ABTC with median overall survival (mOS) <12 months. Given the palliative intent of treatment, itslimited survival gain and notnegligible toxicities itis of paramount importance to properly select pts. Determinantsof immune-inflammation are regarded aspromising prognostic factors in ABTC. Methods: Clinical and laboratory data before starting1-line cht were evaluated in 123 ptswith unresectable locally advancedand metastatic ABTC (intrahepatic,perihilar and distal cholangiocarcinoma and gallbladder cancer) treated from 1st January 2010 to 31st July 2017 at Modena Cancer Centre. Potential prognostic factors were assessed by univariate (Cox proportional hazardunivariate model) and multivariate analyses (multiple Cox proportional hazard regression with the likelihood ratio test). Results: At univariate analysis ECOG PS>0, metastatic disease, gallbladder cancer, no previous surgery, monocht, LDH >upper limit of normal, albumine <3.5gr/dl, absoluteneutrophilcount (ANC) >8000/ml, lymphocyte/monocyteratio (LMR) <2.1, neutrophil/lymphocyte ratio (NLR) >3, platelet/lymphocyte ratio >160, AST> 40IU/L, gamma-glutamyl-transpeptidase >40IU/L, CEA>9.5ng/ml, CA19-9 >700U/Lwere significantly associate with shorter OS. At multivariate analysis, LMR< 2.1, NLR >3,ANC >8000/ml, albumine<3.5gr/dl retained statistical significance as poor prognostic factors. By combining these four variables, three different risk groups were identified: low-risk group (0 factors), intermediate-risk group (1-2factors) and high-risk group (3-4 factors), with mOS of 22, 12,and 5monthsrespectively (P<0.001). The prognostic value of the score was indipendentfrom treatment procedures (doubletvs monocht) and primary tumour site (P<0.001). Conclusions: We developed a cost-effective and easily-available scoring system that discriminates ABTC treated with 1-line cht into three, different, statistically significant prognostic groups. Itcould become ausefultool toadd to established factors for improving pts’selectionin dailypractice.","Source":"Google Scholar","category":"HUMAN","training_data":"A Novel Immune-Inflammatory Score To Predict Survival In Patients (Pts) With Advanced Biliary Tract Cancer (Abtc) Receiving First-Line Chemotherapy (1-Line Cht) Background: Cht isthe mainstay of treatment for ABTC with median overall survival (mOS) <12 months. Given the palliative intent of treatment, itslimited survival gain and notnegligible toxicities itis of paramount importance to properly select pts. Determinantsof immune-inflammation are regarded aspromising prognostic factors in ABTC. Methods: Clinical and laboratory data before starting1-line cht were evaluated in 123 ptswith unresectable locally advancedand metastatic ABTC (intrahepatic,perihilar and distal cholangiocarcinoma and gallbladder cancer) treated from 1st January 2010 to 31st July 2017 at Modena Cancer Centre. Potential prognostic factors were assessed by univariate (Cox proportional hazardunivariate model) and multivariate analyses (multiple Cox proportional hazard regression with the likelihood ratio test). Results: At univariate analysis ECOG PS>0, metastatic disease, gallbladder cancer, no previous surgery, monocht, LDH >upper limit of normal, albumine <3.5gr/dl, absoluteneutrophilcount (ANC) >8000/ml, lymphocyte/monocyteratio (LMR) <2.1, neutrophil/lymphocyte ratio (NLR) >3, platelet/lymphocyte ratio >160, AST> 40IU/L, gamma-glutamyl-transpeptidase >40IU/L, CEA>9.5ng/ml, CA19-9 >700U/Lwere significantly associate with shorter OS. At multivariate analysis, LMR< 2.1, NLR >3,ANC >8000/ml, albumine<3.5gr/dl retained statistical significance as poor prognostic factors. By combining these four variables, three different risk groups were identified: low-risk group (0 factors), intermediate-risk group (1-2factors) and high-risk group (3-4 factors), with mOS of 22, 12,and 5monthsrespectively (P<0.001). The prognostic value of the score was indipendentfrom treatment procedures (doubletvs monocht) and primary tumour site (P<0.001). Conclusions: We developed a cost-effective and easily-available scoring system that discriminates ABTC treated with 1-line cht into three, different, statistically significant prognostic groups. Itcould become ausefultool toadd to established factors for improving pts’selectionin dailypractice. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"high spicy food intake risk cancer meta analysis case control studies background studies association spicy food intake cancer risk reported inconsistent results quantitatively assessed association conducting meta analysis based evidence case control studies methods pubmed embase cochrane library searched eligible publications combined odds ratios 95 confidence interval ci calculated using random fixed effects model methodological quality included articles assessed using newcastle ottawa scale nos data analyzed using stata 11 0 software version 11 0 statacorp college station tx usa subgroup analyses also performed stratification region sex number cases cancer subtype source control group nos score results total 39 studies 28 articles fulfilled inclusion criteria meta analysis 7884 patients cancer 10 142 controls comparison highest versus lowest exposure category study revealed significant 1 76 95 ci 1 35 2 29 spite significant heterogeneity p 0 001 subgroup analyses positive correlation still found gastric cancer different regions different numbers cases different sources control group high quality articles nos score 7 however statistically significant association observed women esophageal cancer gallbladder cancer low quality articles nos score 7 evidence publication bias found conclusions evidence case control studies suggested higher level spicy food intake may associated increased incidence cancer despite significant heterogeneity studies warranted clarify understanding association high spicy food intake risk cancer pubmed","probabilities":0.9799733,"Title":"High Spicy Food Intake and Risk of Cancer: A Meta-analysis of Case-control Studies","Abstract":"BACKGROUND: Studies on the association between spicy food intake and cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on evidence from case-control studies. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for eligible publications. Combined odds ratios (OR s) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. The methodological quality of the included articles was assessed using the Newcastle-Ottawa scale (NOS). All data were analyzed using STATA 11.0 software (version 11.0; StataCorp., College Station, TX, USA). Subgroup analyses were also performed with stratification by region, sex, number of cases, cancer subtype, source of the control group, and NOS score. RESULTS: A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis (7884 patients with cancer and 10,142 controls). Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 (95% CI = 1.35-2.29) in spite of significant heterogeneity (P < 0.001). In the subgroup analyses, this positive correlation was still found for gastric cancer, different regions, different numbers of cases, different sources of the control group, and high-quality articles (NOS score of ≥ 7). However, no statistically significant association was observed for women, esophageal cancer, gallbladder cancer, or low-quality articles (NOS score of <7). No evidence of publication bias was found. CONCLUSIONS: Evidence from case-control studies suggested that a higher level of spicy food intake may be associated with an increased incidence of cancer despite significant heterogeneity. More studies are warranted to clarify our understanding of the association between high spicy food intake and the risk of cancer.","Source":"PubMed","category":"HUMAN","training_data":"High Spicy Food Intake and Risk of Cancer: A Meta-analysis of Case-control Studies BACKGROUND: Studies on the association between spicy food intake and cancer risk have reported inconsistent results. We quantitatively assessed this association by conducting a meta-analysis based on evidence from case-control studies. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for eligible publications. Combined odds ratios (OR s) with their 95% confidence interval (CI) were calculated using a random- or fixed-effects model. The methodological quality of the included articles was assessed using the Newcastle-Ottawa scale (NOS). All data were analyzed using STATA 11.0 software (version 11.0; StataCorp., College Station, TX, USA). Subgroup analyses were also performed with stratification by region, sex, number of cases, cancer subtype, source of the control group, and NOS score. RESULTS: A total 39 studies from 28 articles fulfilled the inclusion criteria for the meta-analysis (7884 patients with cancer and 10,142 controls). Comparison of the highest versus lowest exposure category in each study revealed a significant OR of 1.76 (95% CI = 1.35-2.29) in spite of significant heterogeneity (P < 0.001). In the subgroup analyses, this positive correlation was still found for gastric cancer, different regions, different numbers of cases, different sources of the control group, and high-quality articles (NOS score of ≥ 7). However, no statistically significant association was observed for women, esophageal cancer, gallbladder cancer, or low-quality articles (NOS score of <7). No evidence of publication bias was found. CONCLUSIONS: Evidence from case-control studies suggested that a higher level of spicy food intake may be associated with an increased incidence of cancer despite significant heterogeneity. More studies are warranted to clarify our understanding of the association between high spicy food intake and the risk of cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma treated transarterial yttrium 90 radioembolization moffitt experience purpose evaluate efficacy safety transarterial yttrium 90 glass microsphere radioembolization patients unresectable intrahepatic cholangiocarcinoma icc materials methods retrospective review 85 consecutive patients 41 men 44 women age 73 4 9 3 years performed survival data analyzed kaplan meier method cox regression models log rank test results median overall survival os diagnosis 21 4 months 95 confidence interval ci 16 6 28 4 median os radioembolization 12 0 months 95 ci 8 0 15 2 seven episodes severe toxicity occurred 3 months 6 2 patients partial response 64 2 stable disease 29 6 progressive disease median os radioembolization significantly longer patients eastern cooperative oncology group ecog scores 0 1 patients ecog score 2 18 5 vs 5 5 months p 0012 median os radioembolization significantly longer patients well differentiated histology patients poorly differentiated histology 18 6 vs 9 7 months p 012 patients solitary tumors significantly longer median os radioembolization patients multifocal disease 25 vs 6 1 months p 006 absence extrahepatic metastasis associated significantly increased median os 15 2 vs 6 8 months p 003 increased time diagnosis radioembolization negative predictor os morphology tumor mass forming infiltrative hyper hypo enhancing effect survival post treatment increased cancer antigen 19 9 level increased international normalized ratio decreased albumin increased bilirubin increased aspartate aminotransferase increased model end stage liver disease score significant predictors decreased os conclusions data support therapeutic role radioembolization treatment unresectable icc good efficacy acceptable safety profile stn","probabilities":0.9799733,"Title":"Intrahepatic Cholangiocarcinoma Treated With Transarterial Yttrium-90 Radioembolization-The Moffitt Experience","Abstract":"Purpose: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Materials and methods: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. \r\n\r\n Results: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. \r\n\r\n Conclusions: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile.","Source":"STN","category":"HUMAN","training_data":"Intrahepatic Cholangiocarcinoma Treated With Transarterial Yttrium-90 Radioembolization-The Moffitt Experience Purpose: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). \r\n\r\n Materials and methods: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. \r\n\r\n Results: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. \r\n\r\n Conclusions: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic value tumor marker kinetics palliative chemotherapy patients unresectable gallbladder adenocarcinoma background aims determine prognostic value carcinoembryonic antigen cea carbohydrate antigen ca 19 9 gallbladder cancer gbc palliative chemotherapy methods one hundred twenty three patients pathologically confirmed unresectable gbc included differences serum cea ca 19 9 levels chemotherapy measured receiver operating characteristic curve analysis kaplan meier analyses cea ca 19 9 combined changes performed assess optimal cutoff values survival rates results patients decreased tumor markers significantly better progression free survival pfs overall survival os patients increased tumor markers pre postchemotherapy ca 19 9 ratio highest area curve values predicting 3 month pfs 1 year os multivariate analysis increases serum ca 19 9 palliative chemotherapy patients unresectable gbc independent prognosticator poor pfs os hazard ratios 2 20 p 0 001 1 67 p 0 020 respectively patients increases 10 fold considered progressive disease whereas individuals increases 3 fold likely benefit early imaging follow conclusions ca 19 9 kinetics reliable prognosticator pfs os patients unresectable gbc underwent palliative chemotherapy stn","probabilities":0.9799733,"Title":"Prognostic Value Of Tumor Marker Kinetics During Palliative Chemotherapy In Patients With Unresectable Gallbladder Adenocarcinoma","Abstract":"Background/aims: To determine the prognostic value of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during palliative chemotherapy. \r\n\r\n Methods: One hundred and twenty-three patients with pathologically confirmed unresectable GBC were included. Differences in serum CEA and CA 19-9 levels before and after chemotherapy were measured. Receiver operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9, and combined changes were performed to assess the optimal cutoff values and survival rates. \r\n\r\n Results: Patients with decreased tumor markers had significantly better progression-free survival (PFS) and overall survival (OS) than patients with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In the multivariate analysis, increases in serum CA 19-9 during palliative chemotherapy in patients with unresectable GBC was an independent prognosticator of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020), respectively. Patients with increases ＞10-fold were considered to have progressive disease, whereas individuals with increases ＞3-fold were likely to benefit from early imaging follow-up. \r\n\r\n Conclusions: CA 19-9 kinetics was a reliable prognosticator of PFS and OS in patients with unresectable GBC who underwent palliative chemotherapy.","Source":"STN","category":"HUMAN","training_data":"Prognostic Value Of Tumor Marker Kinetics During Palliative Chemotherapy In Patients With Unresectable Gallbladder Adenocarcinoma Background/aims: To determine the prognostic value of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during palliative chemotherapy. \r\n\r\n Methods: One hundred and twenty-three patients with pathologically confirmed unresectable GBC were included. Differences in serum CEA and CA 19-9 levels before and after chemotherapy were measured. Receiver operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9, and combined changes were performed to assess the optimal cutoff values and survival rates. \r\n\r\n Results: Patients with decreased tumor markers had significantly better progression-free survival (PFS) and overall survival (OS) than patients with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In the multivariate analysis, increases in serum CA 19-9 during palliative chemotherapy in patients with unresectable GBC was an independent prognosticator of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020), respectively. Patients with increases ＞10-fold were considered to have progressive disease, whereas individuals with increases ＞3-fold were likely to benefit from early imaging follow-up. \r\n\r\n Conclusions: CA 19-9 kinetics was a reliable prognosticator of PFS and OS in patients with unresectable GBC who underwent palliative chemotherapy. STN","prediction_labels":"HUMAN"},{"cleaned":"venous thromboembolism vte patients cholangiocarcinoma focus risk factors impact survival background high incidence venous thromboembolism vte observed patients cancer however data available patients cholangiocarcinoma objectives aim study evaluate clinical characteristics risk factors vte investigate whether vte affect survival patients cholangiocarcinoma methods retrospectively reviewed 273 patients diagnosed cholangiocarcinoma january 2004 december 2008 results observed 40 cases vte among 10 patients vte diagnosis 14 cases pulmonary thromboembolism without deep vein thrombosis 18 cases portal vein thrombosis four cases inferior vena cava thrombosis four hepatic vein thrombosis found progression stage c reactive protein chemotherapy significantly associated occurrence vte p 0 022 0 006 0 014 respectively median survival vte non vte groups 13 0 25 0 months respectively log rank test p 0 026 vte unfavorable prognostic factor cholangiocarcinoma hazard ratio 1 626 p 0 042 conclusion study advanced stage c reactive protein treatment chemotherapeutic agents related occurrence vte patients cholangiocarcinoma vte independent unfavorable prognostic factor survivors cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Venous Thromboembolism (Vte) In Patients With Cholangiocarcinoma: Focus On Risk Factors And Impact On Survival","Abstract":"Background: A high incidence of venous thromboembolism (VTE) has been observed in patients with cancer. However, few data are available on patients with cholangiocarcinoma. \r\n\r\n Objectives: The aim of this study was to evaluate the clinical characteristics and risk factors of VTE and to investigate whether VTE would affect the survival of patients with cholangiocarcinoma. \r\n\r\n Methods: We retrospectively reviewed 273 patients who were diagnosed with cholangiocarcinoma from January 2004 to December 2008. \r\n\r\n Results: We observed 40 cases of VTE, among which 10 patients had VTE at diagnosis. There were 14 cases of pulmonary thromboembolism with or without deep vein thrombosis, 18 cases of portal vein thrombosis, four cases of inferior vena cava thrombosis, and four of hepatic vein thrombosis. We found that progression of stage, C-reactive protein, and chemotherapy were significantly associated with the occurrence of VTE (P=0.022, 0.006, and 0.014, respectively). The median survival in the VTE and non-VTE groups were 13.0 and 25.0 months, respectively (log-rank test, P=0.026). VTE was an unfavorable prognostic factor for cholangiocarcinoma (hazard ratio=1.626, P=0.042). \r\n\r\n Conclusion: In our study, advanced stage, C-reactive protein, and treatment with chemotherapeutic agents were related to the occurrence of VTE in patients with cholangiocarcinoma. VTE was an independent unfavorable prognostic factor for survivors of cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Venous Thromboembolism (Vte) In Patients With Cholangiocarcinoma: Focus On Risk Factors And Impact On Survival Background: A high incidence of venous thromboembolism (VTE) has been observed in patients with cancer. However, few data are available on patients with cholangiocarcinoma. \r\n\r\n Objectives: The aim of this study was to evaluate the clinical characteristics and risk factors of VTE and to investigate whether VTE would affect the survival of patients with cholangiocarcinoma. \r\n\r\n Methods: We retrospectively reviewed 273 patients who were diagnosed with cholangiocarcinoma from January 2004 to December 2008. \r\n\r\n Results: We observed 40 cases of VTE, among which 10 patients had VTE at diagnosis. There were 14 cases of pulmonary thromboembolism with or without deep vein thrombosis, 18 cases of portal vein thrombosis, four cases of inferior vena cava thrombosis, and four of hepatic vein thrombosis. We found that progression of stage, C-reactive protein, and chemotherapy were significantly associated with the occurrence of VTE (P=0.022, 0.006, and 0.014, respectively). The median survival in the VTE and non-VTE groups were 13.0 and 25.0 months, respectively (log-rank test, P=0.026). VTE was an unfavorable prognostic factor for cholangiocarcinoma (hazard ratio=1.626, P=0.042). \r\n\r\n Conclusion: In our study, advanced stage, C-reactive protein, and treatment with chemotherapeutic agents were related to the occurrence of VTE in patients with cholangiocarcinoma. VTE was an independent unfavorable prognostic factor for survivors of cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"specific risk factors contributing early late recurrences intrahepatic cholangiocarcinoma curative resection background intrahepatic cholangiocarcinoma icc patients experienced tumor recurrences even curative resection optimal cut time point specific risk factors early late recurrences icc clearly defined objective current study define specific risk factors early late recurrences icc radical hepatectomy methods included study 259 icc patients underwent curative surgery hospital january 2005 december 2009 recurrences patients followed prospectively piecewise regression model minimum p value approach used estimate optimal cut time point early late recurrences cox proportional hazards regression model used identify specific independent risk factors early late recurrences results early late recurrences occurred 130 74 patients respectively 12th month confirmed optimal cut time point early late recurrences cox proportional hazards regression model showed microvascular invasion hr 2 084 95 ci 1 115 3 897 p 0 021 multiple tumors hr 2 071 95 ci 1 185 3 616 p 0 010 abnormal elevation serum ca19 9 hr 1 619 95 ci 1 076 2 437 p 0 021 negative hepatitis b status hr 1 650 95 ci 1 123 2 427 p 0 011 independent risk factors early recurrence hbv dna level 10 6 iu ml hr 1 785 95 ci 1 015 3 141 p 0 044 hepatolithiasis history hr 2 538 95 ci 1 165 5 533 p 0 010 contributed late recurrence independently conclusion specific risk factors mechanisms may relate early late recurrences icc curative resection pubmed","probabilities":0.9799733,"Title":"Specific risk factors contributing to early and late recurrences of intrahepatic cholangiocarcinoma after curative resection","Abstract":"BACKGROUND: Most intrahepatic cholangiocarcinoma (ICC) patients experienced tumor recurrences even after curative resection, but the optimal cut-off time point and the specific risk factors for early and late recurrences of ICC have not been clearly defined. The objective of the current study was to define specific risk factors for early and late recurrences of ICC after radical hepatectomy. METHODS: Included in this study were 259 ICC patients who underwent curative surgery at our hospital between January 2005 and December 2009. Recurrences in these patients were followed-up prospectively. Piecewise regression model and the minimum P value approach were used to estimate the optimal cut-off time point for early and late recurrences. Then, Cox's proportional hazards regression model was used to identify specific independent risk factors for early and late recurrences. RESULTS: Early and late recurrences occurred in 130 and 74 patients, respectively, and the 12th month was confirmed as the optimal cut-off time point for early and late recurrences. Cox's proportional hazards regression model showed that microvascular invasion (HR = 2.084, 95% CI 1.115-3.897, P = 0.021), multiple tumors (HR = 2.071, 95% CI 1.185-3.616, P = 0.010), abnormal elevation of serum CA19-9 (HR = 1.619, 95% CI 1.076-2.437, P = 0.021), and the negative hepatitis B status (HR = 1.650, 95% CI 1.123-2.427, P = 0.011) were independent risk factors for early recurrence, and HBV-DNA level > 10(6) IU/mL (HR = 1.785, 95% CI 1.015-3.141, P = 0.044) and a hepatolithiasis history (HR = 2.538, 95% CI 1.165-5.533, P = 0.010) contributed to late recurrence independently. CONCLUSION: Specific risk factors and mechanisms may relate to early and late recurrences of ICC after curative resection.","Source":"PubMed","category":"HUMAN","training_data":"Specific risk factors contributing to early and late recurrences of intrahepatic cholangiocarcinoma after curative resection BACKGROUND: Most intrahepatic cholangiocarcinoma (ICC) patients experienced tumor recurrences even after curative resection, but the optimal cut-off time point and the specific risk factors for early and late recurrences of ICC have not been clearly defined. The objective of the current study was to define specific risk factors for early and late recurrences of ICC after radical hepatectomy. METHODS: Included in this study were 259 ICC patients who underwent curative surgery at our hospital between January 2005 and December 2009. Recurrences in these patients were followed-up prospectively. Piecewise regression model and the minimum P value approach were used to estimate the optimal cut-off time point for early and late recurrences. Then, Cox's proportional hazards regression model was used to identify specific independent risk factors for early and late recurrences. RESULTS: Early and late recurrences occurred in 130 and 74 patients, respectively, and the 12th month was confirmed as the optimal cut-off time point for early and late recurrences. Cox's proportional hazards regression model showed that microvascular invasion (HR = 2.084, 95% CI 1.115-3.897, P = 0.021), multiple tumors (HR = 2.071, 95% CI 1.185-3.616, P = 0.010), abnormal elevation of serum CA19-9 (HR = 1.619, 95% CI 1.076-2.437, P = 0.021), and the negative hepatitis B status (HR = 1.650, 95% CI 1.123-2.427, P = 0.011) were independent risk factors for early recurrence, and HBV-DNA level > 10(6) IU/mL (HR = 1.785, 95% CI 1.015-3.141, P = 0.044) and a hepatolithiasis history (HR = 2.538, 95% CI 1.165-5.533, P = 0.010) contributed to late recurrence independently. CONCLUSION: Specific risk factors and mechanisms may relate to early and late recurrences of ICC after curative resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"diagnostic accuracy serum ca19 9 patients cholangiocarcinoma systematic review meta analysis background cholangiocarcinoma cca relatively rare cancer worldwide however incidence extremely high asia numerous studies reported serum carbohydrate antigen 19 9 ca19 9 plays role diagnosis cca patients however published data inconclusive aim meta analysis provide systematic review diagnostic performance ca19 9 cca material methods searched public databases including pubmed web science embase chinese national knowledge infrastructure cnki wanfang databases articles evaluating diagnostic accuracy serum ca19 9 predict cca diagnostic sensitivity sen specificity spe positive likelihood ratio plr negative likelihood ratio nlr diagnostic odds ratio dor summary receiver operating characteristic curve sroc pooled meta disc 1 4 software results total 31 articles met inclusion criteria including 1 264 patients 2 039 controls pooled sen spe plr nlr dor 0 72 95 ci 0 70 0 75 0 84 95 ci 0 82 0 85 4 93 95 ci 3 67 6 64 0 35 95 ci 0 30 0 41 15 10 95 ci 10 70 21 32 respectively area sroc curve 0 8300 subgroup analyses based different control type geographical location sample size revealed diagnostic accuracy ca19 9 tends different control type showed low sensitivity european patients small size group conclusions serum ca19 9 useful non invasive biomarker cca detection may become clinically useful tool identify high risk patients pubmed","probabilities":0.9799733,"Title":"Diagnostic Accuracy of Serum CA19-9 in Patients with Cholangiocarcinoma: A Systematic Review and Meta-Analysis","Abstract":"BACKGROUND Cholangiocarcinoma (CCA) is a relatively rare cancer worldwide; however, its incidence is extremely high in Asia. Numerous studies reported that serum carbohydrate antigen 19-9 (CA19-9) plays a role in the diagnosis of CCA patients. However, published data are inconclusive. The aim of this meta-analysis was to provide a systematic review of the diagnostic performance of CA19-9 for CCA. MATERIAL AND METHODS We searched the public databases including PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases for articles evaluating the diagnostic accuracy of serum CA19-9 to predict CCA. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. RESULTS A total of 31 articles met the inclusion criteria, including 1,264 patients and 2,039 controls. The pooled SEN, SPE, PLR, NLR, and DOR were 0.72 (95% CI: 0.70-0.75), 0.84 (95% CI: 0.82-0.85), 4.93 (95% CI, 3.67-6.64), 0.35 (95%CI, 0.30-0.41), and 15.10 (95% CI, 10.70-21.32), respectively. The area under SROC curve was 0.8300. The subgroup analyses based on different control type, geographical location, and sample size revealed that the diagnostic accuracy of CA19-9 tends to be same in different control type, but showed low sensitivity in European patients and small size group. CONCLUSIONS Serum CA19-9 is a useful non-invasive biomarker for CCA detection and may become a clinically useful tool to identify high-risk patients.","Source":"PubMed","category":"HUMAN","training_data":"Diagnostic Accuracy of Serum CA19-9 in Patients with Cholangiocarcinoma: A Systematic Review and Meta-Analysis BACKGROUND Cholangiocarcinoma (CCA) is a relatively rare cancer worldwide; however, its incidence is extremely high in Asia. Numerous studies reported that serum carbohydrate antigen 19-9 (CA19-9) plays a role in the diagnosis of CCA patients. However, published data are inconclusive. The aim of this meta-analysis was to provide a systematic review of the diagnostic performance of CA19-9 for CCA. MATERIAL AND METHODS We searched the public databases including PubMed, Web of Science, Embase, Chinese National Knowledge Infrastructure (CNKI), and WANFANG databases for articles evaluating the diagnostic accuracy of serum CA19-9 to predict CCA. The diagnostic sensitivity (SEN), specificity (SPE), positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and summary receiver operating characteristic curve (SROC) were pooled by Meta-DiSc 1.4 software. RESULTS A total of 31 articles met the inclusion criteria, including 1,264 patients and 2,039 controls. The pooled SEN, SPE, PLR, NLR, and DOR were 0.72 (95% CI: 0.70-0.75), 0.84 (95% CI: 0.82-0.85), 4.93 (95% CI, 3.67-6.64), 0.35 (95%CI, 0.30-0.41), and 15.10 (95% CI, 10.70-21.32), respectively. The area under SROC curve was 0.8300. The subgroup analyses based on different control type, geographical location, and sample size revealed that the diagnostic accuracy of CA19-9 tends to be same in different control type, but showed low sensitivity in European patients and small size group. CONCLUSIONS Serum CA19-9 is a useful non-invasive biomarker for CCA detection and may become a clinically useful tool to identify high-risk patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"skeletal muscle mass predicts prognosis patients intrahepatic cholangiocarcinoma background studied prognostic impact sarcopenia hepatic resection intrahepatic cholangiocarcinoma icc methods sixty one patients underwent surgery icc 2000 2017 analyzed retrospectively psoas muscle areas measured ct scans third lumbar vertebra areas less sex specific median deemed low skeletal muscle masses smms results low smm patients significantly often older p 0 002 high smm patients lower serum albumin p 0 004 higher serum c reactive protein crp p 0 002 higher carbohydrate antigen 19 9 p 0 001 five year overall survival rates 72 5 17 6 5 year recurrence free survival rates 58 6 21 1 respectively high low smm patients multivariable analysis revealed low smm predicted unfavorable prognoses smm associated immune nutritional status e g prognostic nutritional index glasgow prognostic score crp albumin ratio conclusion low smm related worse surgical outcomes patients icc following hepatic resection pubmed","probabilities":0.9799733,"Title":"Skeletal muscle mass predicts the prognosis of patients with intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: We studied the prognostic impact of sarcopenia after hepatic resection for intrahepatic cholangiocarcinoma (ICC). METHODS: Sixty-one patients who underwent surgery for ICC during 2000-2017 were analyzed retrospectively. Psoas muscle areas were measured on CT scans at the third lumbar vertebra. Areas less than the sex-specific median were deemed low skeletal muscle masses (SMMs). RESULTS: Low-SMM patients were significantly more often older (p = 0.002) than high-SMM patients, had lower serum albumin (p = 0.004), higher serum C-reactive protein (CRP) (p = 0.002), and higher carbohydrate antigen 19-9 (p < 0.001). Five-year overall survival rates were 72.5% and 17.6% and 5-year recurrence-free survival rates were 58.6% and 21.1%, respectively, in high- and low-SMM patients. Multivariable analysis revealed that low SMM predicted unfavorable prognoses. SMM was associated with immune nutritional status (e.g., prognostic nutritional index, Glasgow prognostic score, CRP/albumin ratio). CONCLUSION: Low SMM was related to worse surgical outcomes in patients with ICC following hepatic resection.","Source":"PubMed","category":"HUMAN","training_data":"Skeletal muscle mass predicts the prognosis of patients with intrahepatic cholangiocarcinoma BACKGROUND: We studied the prognostic impact of sarcopenia after hepatic resection for intrahepatic cholangiocarcinoma (ICC). METHODS: Sixty-one patients who underwent surgery for ICC during 2000-2017 were analyzed retrospectively. Psoas muscle areas were measured on CT scans at the third lumbar vertebra. Areas less than the sex-specific median were deemed low skeletal muscle masses (SMMs). RESULTS: Low-SMM patients were significantly more often older (p = 0.002) than high-SMM patients, had lower serum albumin (p = 0.004), higher serum C-reactive protein (CRP) (p = 0.002), and higher carbohydrate antigen 19-9 (p < 0.001). Five-year overall survival rates were 72.5% and 17.6% and 5-year recurrence-free survival rates were 58.6% and 21.1%, respectively, in high- and low-SMM patients. Multivariable analysis revealed that low SMM predicted unfavorable prognoses. SMM was associated with immune nutritional status (e.g., prognostic nutritional index, Glasgow prognostic score, CRP/albumin ratio). CONCLUSION: Low SMM was related to worse surgical outcomes in patients with ICC following hepatic resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"perineural invasion preoperative serum ca19 9 predictors survival biliary tract cancer background billiary tract cancer requires invasive surgical procedures cure risk factors related patient prognosis remain controversial patients methods 111 patients underwent resection extrahepatic biliary tract tumors 1986 2010 records 88 ampullary extrahepatic bile duct cancer included information evaluation clinicopathological factors employed multivariate analysis results univariate analysis significant prognostic factors poor survival unrelated tnm factors preoperative biliary drainage high preoperative ca19 9 value high preoperative cea value lymphatic invasion perineural invasion macroscopic growth pattern histology operative procedures surgery tumor persistence high postoperative ca19 9 value postoperative chemotherapy multivariate analysis perineural invasion p 0 025 prognostic factor independent stage survival patients biliary tract cancer including ampullary cancer ampullary cancer excluded perineural invasion preoperative ca19 9 remaining prognostic factors independent stage combination factors accurately identify long term short term survivors biliary tract cancer conclusion present study knowledge first time shows perineural invasion preoperative ca19 9 important prognostic factors biliary tract cancer beneficial clinical clarification optimal strategies type cancer stn","probabilities":0.9799733,"Title":"Perineural Invasion And Preoperative Serum Ca19-9 As Predictors Of Survival In Biliary Tract Cancer","Abstract":"Background: Billiary tract cancer requires invasive surgical procedures for cure, and the risk factors related to patient prognosis remain controversial. \r\n\r\n Patients and methods: Out of the 111 patients who underwent resection of extrahepatic biliary tract tumors from 1986 to 2010, the records for 88 with both ampullary and extrahepatic bile duct cancer, which included all information for evaluation of the clinicopathological factors, were employed in a multivariate analysis. \r\n\r\n Results: On univariate analysis, significant prognostic factors of poor survival unrelated to TNM factors were preoperative biliary drainage, high preoperative CA19-9 value, high preoperative CEA value, lymphatic invasion, perineural invasion, macroscopic growth pattern, histology, operative procedures (surgery), tumor persistence, high postoperative CA19-9 value, and postoperative chemotherapy. On multivariate analysis, perineural invasion (p=0.025) was the only prognostic factor independent of stage, for survival of patients with biliary tract cancer including ampullary cancer. When ampullary cancer was excluded, both perineural invasion and preoperative CA19-9 were the remaining prognostic factors independent of stage. The combination of both factors can very accurately identify long-term and short-term survivors of biliary tract cancer. \r\n\r\n Conclusion: The present study, to our knowledge, for the first time shows that both perineural invasion and preoperative CA19-9 are important prognostic factors in biliary tract cancer, and this would be beneficial for clinical clarification of the optimal strategies for this type of cancer.","Source":"STN","category":"HUMAN","training_data":"Perineural Invasion And Preoperative Serum Ca19-9 As Predictors Of Survival In Biliary Tract Cancer Background: Billiary tract cancer requires invasive surgical procedures for cure, and the risk factors related to patient prognosis remain controversial. \r\n\r\n Patients and methods: Out of the 111 patients who underwent resection of extrahepatic biliary tract tumors from 1986 to 2010, the records for 88 with both ampullary and extrahepatic bile duct cancer, which included all information for evaluation of the clinicopathological factors, were employed in a multivariate analysis. \r\n\r\n Results: On univariate analysis, significant prognostic factors of poor survival unrelated to TNM factors were preoperative biliary drainage, high preoperative CA19-9 value, high preoperative CEA value, lymphatic invasion, perineural invasion, macroscopic growth pattern, histology, operative procedures (surgery), tumor persistence, high postoperative CA19-9 value, and postoperative chemotherapy. On multivariate analysis, perineural invasion (p=0.025) was the only prognostic factor independent of stage, for survival of patients with biliary tract cancer including ampullary cancer. When ampullary cancer was excluded, both perineural invasion and preoperative CA19-9 were the remaining prognostic factors independent of stage. The combination of both factors can very accurately identify long-term and short-term survivors of biliary tract cancer. \r\n\r\n Conclusion: The present study, to our knowledge, for the first time shows that both perineural invasion and preoperative CA19-9 are important prognostic factors in biliary tract cancer, and this would be beneficial for clinical clarification of the optimal strategies for this type of cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"incidence prevalence mortality hepatobiliary pancreatic malignancies global regional level 1990 2016 gbd 2016 study background cancer second common cause death aim determine incidence prevalence mortality trends hpb malignancy global regional levels report disability adjusted life years dalys years lost disability yld methods global burden disease gbd 2016 dataset interrogated end point variables age sex year geography 1990 2016 data modeled dismod mr 2 1 results expressed age standardized rates asr results global asir primary liver pancreatic neoplasm rose 12 49 14 55 6 11 6 37 1990 2016 increase 17 87 6 25 respectively contrast asir biliary cancer decreased 3 71 2 8 decrease 24 5 addition global aspr primary liver pancreatic biliary cancers increased 75 27 13 44 31 15 respectively global asmr stayed constant primary liver pancreatic cancer interestingly biliary cancer saw global decrease asmr 23 77 global daly decreased primary liver pancreatic biliary cancers contrast yld rose primary liver cancers 22 3 stayed relatively constant pancreatic cancer yet fell slightly biliary cancer high income asia pacific highest asr incidence pancreatic biliary cancers yet second highest incidence primary liver cancers conclusions incidence prevalence hpb malignancies seen overall increased change mortality rates albeit significant geographical variation daly decreased hpb neoplasms google scholar","probabilities":0.9799733,"Title":"Incidence Prevalence And Mortality Of Hepatobiliary & Pancreatic Malignancies At The Global And Regional Level: 1990 To 2016 Gbd 2016 Study","Abstract":"Background: Cancer is the second most common cause of death. We aim to determine the incidence, prevalence, and mortality trends for HPB malignancy at a Global/Regional levels. We report on disability-adjusted life years (DALYs), and years lost to disability (YLD).\nMethods: The Global Burden of Disease (GBD) 2016 dataset was interrogated for end point variables by age, sex, year, and geography from 1990 to 2016. Data was modeled in DisMod-MR 2.1. Results are expressed as age-standardized rates (ASR).\nResults: The global ASIR for primary liver and pancreatic neoplasm rose from 12.49 to 14.55 and 6.11 to 6.37 (1990 to 2016); an increase of 17.87% and 6.25%, respectively. In contrast, the ASIR for biliary cancer decreased from 3.71 to 2.8, a decrease of 24.5%. In addition, the global ASPR for primary liver, pancreatic, and biliary cancers all increased 75.27%, 13.44%, and 31.15%, respectively. Global ASMR stayed constant for primary liver and pancreatic cancer. Interestingly, biliary cancer saw a global decrease in ASMR of 23.77%. The global DALY's decreased for primary liver, pancreatic, and biliary cancers. In contrast, the YLD rose for primary liver cancers 22.3%, stayed relatively constant for pancreatic cancer, yet fell slightly for biliary cancer. High-Income Asia Pacific had the highest ASR of incidence for pancreatic and biliary cancers, yet was the second highest incidence of primary liver cancers.\nConclusions: The incidence/prevalence of HPB malignancies has seen an overall increased with no change in mortality rates, albeit a significant geographical variation. DALY's have decreased for HPB neoplasms.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidence Prevalence And Mortality Of Hepatobiliary & Pancreatic Malignancies At The Global And Regional Level: 1990 To 2016 Gbd 2016 Study Background: Cancer is the second most common cause of death. We aim to determine the incidence, prevalence, and mortality trends for HPB malignancy at a Global/Regional levels. We report on disability-adjusted life years (DALYs), and years lost to disability (YLD).\nMethods: The Global Burden of Disease (GBD) 2016 dataset was interrogated for end point variables by age, sex, year, and geography from 1990 to 2016. Data was modeled in DisMod-MR 2.1. Results are expressed as age-standardized rates (ASR).\nResults: The global ASIR for primary liver and pancreatic neoplasm rose from 12.49 to 14.55 and 6.11 to 6.37 (1990 to 2016); an increase of 17.87% and 6.25%, respectively. In contrast, the ASIR for biliary cancer decreased from 3.71 to 2.8, a decrease of 24.5%. In addition, the global ASPR for primary liver, pancreatic, and biliary cancers all increased 75.27%, 13.44%, and 31.15%, respectively. Global ASMR stayed constant for primary liver and pancreatic cancer. Interestingly, biliary cancer saw a global decrease in ASMR of 23.77%. The global DALY's decreased for primary liver, pancreatic, and biliary cancers. In contrast, the YLD rose for primary liver cancers 22.3%, stayed relatively constant for pancreatic cancer, yet fell slightly for biliary cancer. High-Income Asia Pacific had the highest ASR of incidence for pancreatic and biliary cancers, yet was the second highest incidence of primary liver cancers.\nConclusions: The incidence/prevalence of HPB malignancies has seen an overall increased with no change in mortality rates, albeit a significant geographical variation. DALY's have decreased for HPB neoplasms. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological features gallbladder papillary adenocarcinoma although patients gallbladder papillary adenocarcinoma gbpa appear better prognoses patients pathological subtypes gallbladder carcinoma gbc clinicopathological features outcomes gbpa fully explored study therefore analyzed clinicopathological characteristics outcomes gbpa study included 16 patients gbpa 101 gallbladder adenocarcinoma gba otherwise specified nos diagnosed pathologically surgical resection clinicopathological survival data retrospectively collected compared fever significantly common gbpa 7 16 vs 10 101 p 0 000 serum carbohydrate antigen 19 9 level increased 1 9 patients gbpa 39 76 gba p 0 022 patients gbpa underwent curative resection 15 16 vs 54 101 p 0 009 pathologically patients gbpa much earlier tumor 4 situ 8 t1 p 0 000 tumor node metastases tnm stages p 0 000 overall 1 3 5 year survival rates significantly higher patients gbpa 100 76 9 76 9 respectively patients gba 72 2 38 8 31 0 respectively p 0 001 preoperative jaundice odds ratio 7 69 95 confidence interval 1 53 38 76 p 0 013 significant prognostic factor patients gba longer significant patients gba gbpa pooled together clinicopathological features patients gbpa differed patients gba otherwise specified pooling patients may mask prognostic factors group pubmed","probabilities":0.9799733,"Title":"Clinicopathological features of gallbladder papillary adenocarcinoma","Abstract":"Although patients with gallbladder papillary adenocarcinoma (GBPA) appear to have better prognoses than patients with other pathological subtypes of gallbladder carcinoma (GBC), the clinicopathological features and outcomes of GBPA have not been fully explored. This study therefore analyzed the clinicopathological characteristics and outcomes of GBPA.This study included 16 patients with GBPA and 101 with gallbladder adenocarcinoma (GBA) not otherwise specified (NOS), all diagnosed pathologically after surgical resection. Clinicopathological and survival data were retrospectively collected and compared. Fever was significantly more common in GBPA (7/16 vs 10/101; P = 0.000). Serum carbohydrate antigen 19-9 level was increased in 1 of 9 patients with GBPA and 39 of 76 with GBA (P = 0.022). More patients with GBPA underwent curative resection (15/16 vs 54/101; P = 0.009). Pathologically, patients with GBPA were at much earlier tumor (T) (4 in situ, 8 T1; P = 0.000) and Tumor, Node, Metastases (TNM) stages (P = 0.000). The overall 1-, 3-, and 5-year survival rates were significantly higher in patients with GBPA (100%, 76.9%, and 76.9%, respectively), than in patients with GBA (72.2%, 38.8%, and 31.0%, respectively; P = 0.001). Preoperative jaundice (odds ratio 7.69; 95% confidence interval, 1.53-38.76; P = 0.013) was a significant prognostic factor in patients with GBA, but was no longer significant when the patients with GBA and GBPA were pooled together. The clinicopathological features of patients with GBPA differed from those in patients with GBA (not otherwise specified). Pooling of patients may mask prognostic factors in each group.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological features of gallbladder papillary adenocarcinoma Although patients with gallbladder papillary adenocarcinoma (GBPA) appear to have better prognoses than patients with other pathological subtypes of gallbladder carcinoma (GBC), the clinicopathological features and outcomes of GBPA have not been fully explored. This study therefore analyzed the clinicopathological characteristics and outcomes of GBPA.This study included 16 patients with GBPA and 101 with gallbladder adenocarcinoma (GBA) not otherwise specified (NOS), all diagnosed pathologically after surgical resection. Clinicopathological and survival data were retrospectively collected and compared. Fever was significantly more common in GBPA (7/16 vs 10/101; P = 0.000). Serum carbohydrate antigen 19-9 level was increased in 1 of 9 patients with GBPA and 39 of 76 with GBA (P = 0.022). More patients with GBPA underwent curative resection (15/16 vs 54/101; P = 0.009). Pathologically, patients with GBPA were at much earlier tumor (T) (4 in situ, 8 T1; P = 0.000) and Tumor, Node, Metastases (TNM) stages (P = 0.000). The overall 1-, 3-, and 5-year survival rates were significantly higher in patients with GBPA (100%, 76.9%, and 76.9%, respectively), than in patients with GBA (72.2%, 38.8%, and 31.0%, respectively; P = 0.001). Preoperative jaundice (odds ratio 7.69; 95% confidence interval, 1.53-38.76; P = 0.013) was a significant prognostic factor in patients with GBA, but was no longer significant when the patients with GBA and GBPA were pooled together. The clinicopathological features of patients with GBPA differed from those in patients with GBA (not otherwise specified). Pooling of patients may mask prognostic factors in each group. PubMed","prediction_labels":"HUMAN"},{"cleaned":"meta analysis prognostic factors overall survival patients resected hilar cholangiocarcinoma background hilar cholangiocarcinoma staged using ajcc staging system numerous prognostically important histopathological demographic characteristics reported objective meta analysis assess statistically effect postresectional tumour characteristics overall survival patients undergoing attempted radical curative resection hilar cholangiocarcinoma methods relevant studies identified searching ovid medline pubmed databases search limited studies published 2009 2017 papers referring intrahepatic distal cholangiocarcinoma excluded review data extraction used standard parmar modifications determine pooled univariable hazard ratios hrs results twenty four articles containing 4599 patients assessed quantitatively pooled analyses age hr 1 16 95 per cent c 1 04 1 28 category hr 1 49 1 30 1 70 lymph node involvement hr 1 78 1 65 1 93 microvascular invasion hr 1 49 1 34 1 68 perineural invasion hr 1 54 1 40 1 68 tumour differentiation hr 1 54 1 38 1 72 significant prognostic factors low heterogeneity portal vein resection hr 1 54 1 15 1 70 resection margin status hr 1 77 1 57 1 99 significant effects high heterogeneity sex tumour size preoperative carbohydrate antigen 19 9 levels statistically significant effect postoperative prognosis conclusion several tumour biological variables included seventh edition ajcc classification affect overall survival require incorporation prognostic models ensure personalized approach prognostication treatment pubmed","probabilities":0.9799733,"Title":"Meta-analysis of prognostic factors for overall survival in patients with resected hilar cholangiocarcinoma","Abstract":"BACKGROUND: Hilar cholangiocarcinoma is staged using the AJCC staging system. Numerous other prognostically important histopathological and demographic characteristics have been reported. The objective of this meta-analysis was to assess statistically the effect of postresectional tumour characteristics on overall survival of patients undergoing attempted radical curative resection for hilar cholangiocarcinoma. METHODS: Relevant studies were identified by searching the Ovid MEDLINE and PubMed databases. The search was limited to studies published between 2009 and 2017. Papers referring to intrahepatic or distal cholangiocarcinoma were excluded from review. Data extraction used standard Parmar modifications to determine pooled univariable hazard ratios (HRs). RESULTS: Twenty-four articles, containing 4599 patients, were assessed quantitatively. In pooled analyses, age (HR 1·16, 95 per cent c.i. 1·04 to 1·28), T category (HR 1·49, 1·30 to 1·70), lymph node involvement (HR 1·78, 1·65 to 1·93), microvascular invasion (HR 1·49, 1·34 to 1·68), perineural invasion (HR 1·54, 1·40 to 1·68) and tumour differentiation (HR 1·54, 1·38 to 1·72) were significant prognostic factors, with low heterogeneity. Portal vein resection (HR 1·54, 1·15 to 1·70) and resection margin status (HR 1·77, 1·57 to 1·99) had significant effects, but with high heterogeneity. Sex, tumour size and preoperative carbohydrate antigen 19-9 levels did not have a statistically significant effect on postoperative prognosis. CONCLUSION: Several tumour biological variables not included in the seventh edition of the AJCC classification affect overall survival. These require incorporation into prognostic models to ensure a personalized approach to prognostication and treatment.","Source":"PubMed","category":"HUMAN","training_data":"Meta-analysis of prognostic factors for overall survival in patients with resected hilar cholangiocarcinoma BACKGROUND: Hilar cholangiocarcinoma is staged using the AJCC staging system. Numerous other prognostically important histopathological and demographic characteristics have been reported. The objective of this meta-analysis was to assess statistically the effect of postresectional tumour characteristics on overall survival of patients undergoing attempted radical curative resection for hilar cholangiocarcinoma. METHODS: Relevant studies were identified by searching the Ovid MEDLINE and PubMed databases. The search was limited to studies published between 2009 and 2017. Papers referring to intrahepatic or distal cholangiocarcinoma were excluded from review. Data extraction used standard Parmar modifications to determine pooled univariable hazard ratios (HRs). RESULTS: Twenty-four articles, containing 4599 patients, were assessed quantitatively. In pooled analyses, age (HR 1·16, 95 per cent c.i. 1·04 to 1·28), T category (HR 1·49, 1·30 to 1·70), lymph node involvement (HR 1·78, 1·65 to 1·93), microvascular invasion (HR 1·49, 1·34 to 1·68), perineural invasion (HR 1·54, 1·40 to 1·68) and tumour differentiation (HR 1·54, 1·38 to 1·72) were significant prognostic factors, with low heterogeneity. Portal vein resection (HR 1·54, 1·15 to 1·70) and resection margin status (HR 1·77, 1·57 to 1·99) had significant effects, but with high heterogeneity. Sex, tumour size and preoperative carbohydrate antigen 19-9 levels did not have a statistically significant effect on postoperative prognosis. CONCLUSION: Several tumour biological variables not included in the seventh edition of the AJCC classification affect overall survival. These require incorporation into prognostic models to ensure a personalized approach to prognostication and treatment. PubMed","prediction_labels":"HUMAN"},{"cleaned":"risk incidental gallbladder cancer negligible macroscopically normal cholecystectomy specimens background cholecystectomy usually carried benign indications perform routine histopathologic examination detect incidental gallbladder cancer gbc methods cholecystectomies performed four hospitals helsinki metropolitan area 2010 2012 analyzed retrospectively patients preoperative suspicion neoplasia active malignancy cholecystectomy performed secondary procedure excluded results total 2034 cholecystectomies included ten patients 0 5 gbc identified associated macroscopic finding including local hardness n 1 thickened wall n 5 acute inflammation necrosis n 1 suspected neoplasia n 3 gbc found macroscopically normal gallbladders n 1464 ten patients gbc five underwent subsequent liver resection four metastatic disease one locally advanced inoperable disease three five patients underwent liver resection alive disease free final follow median 48 months remaining seven patients gbc died disease median survival 14 months range 10 48 months conclusions routine histopathologic examination macroscopically normal gallbladder improve diagnosis gbc histopathological examination however mandatory macroscopic abnormality present pubmed","probabilities":0.9799733,"Title":"The risk of incidental gallbladder cancer is negligible in macroscopically normal cholecystectomy specimens","Abstract":"BACKGROUND: Cholecystectomy is usually carried out for benign indications. Most perform routine histopathologic examination to detect incidental gallbladder cancer (GBC). METHODS: Cholecystectomies performed at four hospitals in the Helsinki Metropolitan Area during 2010-2012 were analyzed retrospectively. Patients with preoperative suspicion of neoplasia, active malignancy, or in whom cholecystectomy was performed as a secondary procedure were excluded. RESULTS: A total of 2034 cholecystectomies were included. In ten patients (0.5%), GBC was identified, each with an associated macroscopic finding, including local hardness (n = 1), a thickened wall (n = 5), acute inflammation and necrosis (n = 1), or suspected neoplasia (n = 3). No GBC was found in macroscopically normal gallbladders (n = 1464). Of the ten patients with GBC, five underwent subsequent liver resection, four had metastatic disease, and one had locally advanced inoperable disease. Three of the five patients who underwent liver resection were alive and disease-free at final follow-up (median 48 months). The remaining seven patients with GBC died of the disease, with a median survival of 14 months (range 10-48 months). CONCLUSIONS: Routine histopathologic examination of a macroscopically normal gallbladder does not improve diagnosis of GBC. A histopathological examination is, however, mandatory when a macroscopic abnormality is present.","Source":"PubMed","category":"HUMAN","training_data":"The risk of incidental gallbladder cancer is negligible in macroscopically normal cholecystectomy specimens BACKGROUND: Cholecystectomy is usually carried out for benign indications. Most perform routine histopathologic examination to detect incidental gallbladder cancer (GBC). METHODS: Cholecystectomies performed at four hospitals in the Helsinki Metropolitan Area during 2010-2012 were analyzed retrospectively. Patients with preoperative suspicion of neoplasia, active malignancy, or in whom cholecystectomy was performed as a secondary procedure were excluded. RESULTS: A total of 2034 cholecystectomies were included. In ten patients (0.5%), GBC was identified, each with an associated macroscopic finding, including local hardness (n = 1), a thickened wall (n = 5), acute inflammation and necrosis (n = 1), or suspected neoplasia (n = 3). No GBC was found in macroscopically normal gallbladders (n = 1464). Of the ten patients with GBC, five underwent subsequent liver resection, four had metastatic disease, and one had locally advanced inoperable disease. Three of the five patients who underwent liver resection were alive and disease-free at final follow-up (median 48 months). The remaining seven patients with GBC died of the disease, with a median survival of 14 months (range 10-48 months). CONCLUSIONS: Routine histopathologic examination of a macroscopically normal gallbladder does not improve diagnosis of GBC. A histopathological examination is, however, mandatory when a macroscopic abnormality is present. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance platelet lymphocyte ratio cholangiocarcinoma meta analysis introduction pretreatment platelet lymphocyte ratio plr considered prognostic factor various cancers however application plr assessment patients cholangiocarcinoma remains controversial study aimed evaluate prognostic value pretreatment plr cholangiocarcinoma methods systematic search performed medline embase cochrane library identify studies assessing prognostic significance pretreatment plr cholangiocarcinoma three databases searched inception august 5 2018 primary outcome overall survival os secondary outcomes recurrence free survival rfs progression free survival pfs pooled hazard ratios hrs odds ratios ors 95 confidence intervals cis calculated using random effects models results total 9 studies including 2395 patients finally enrolled meta analysis based inclusion exclusion criteria included studies retrospective observational cohorts elevated plr predicted poor os hr 1 38 95 ci 1 19 1 62 p 0 001 rfs pfs hr 1 55 95 ci 1 27 1 88 p 0 001 moreover elevated plr highly associated male sex male versus female 0 59 95 ci 0 44 0 80 p 0 001 r1 resection margin 2 09 95 ci 1 24 3 54 p 0 006 conclusion present meta analysis demonstrated pretreatment plr might serve useful prognostic biomarker cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic Significance of Platelet-to-Lymphocyte Ratio in Cholangiocarcinoma: A Meta-Analysis","Abstract":"INTRODUCTION: Pretreatment platelet-to-lymphocyte ratio (PLR) has been considered a prognostic factor in various cancers. However, the application of PLR in the assessment of patients with cholangiocarcinoma remains controversial. This study aimed to evaluate the prognostic value of pretreatment PLR in cholangiocarcinoma. METHODS: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library to identify studies assessing the prognostic significance of the pretreatment PLR in cholangiocarcinoma. Three databases were searched from inception to August 5, 2018. The primary outcome was overall survival (OS), and the secondary outcomes were recurrence-free survival (RFS) and progression-free survival (PFS). Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: A total of 9 studies including 2395 patients were finally enrolled in the meta-analysis based on the inclusion and exclusion criteria. All of the included studies were retrospective observational cohorts. Elevated PLR predicted poor OS (HR: 1.38, 95% CI: 1.19-1.62, P < 0.001) and RFS or PFS (HR = 1.55; 95% CI = 1.27-1.88; P < 0.001). Moreover, elevated PLR was highly associated with male sex (male versus female OR = 0.59, 95% CI: 0.44-0.80, P < 0.001) and R1 resection margin (OR = 2.09, 95% CI: 1.24-3.54, P = 0.006). CONCLUSION: The present meta-analysis demonstrated that pretreatment PLR might serve as a useful prognostic biomarker in cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Significance of Platelet-to-Lymphocyte Ratio in Cholangiocarcinoma: A Meta-Analysis INTRODUCTION: Pretreatment platelet-to-lymphocyte ratio (PLR) has been considered a prognostic factor in various cancers. However, the application of PLR in the assessment of patients with cholangiocarcinoma remains controversial. This study aimed to evaluate the prognostic value of pretreatment PLR in cholangiocarcinoma. METHODS: A systematic search was performed in MEDLINE, EMBASE, and Cochrane Library to identify studies assessing the prognostic significance of the pretreatment PLR in cholangiocarcinoma. Three databases were searched from inception to August 5, 2018. The primary outcome was overall survival (OS), and the secondary outcomes were recurrence-free survival (RFS) and progression-free survival (PFS). Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: A total of 9 studies including 2395 patients were finally enrolled in the meta-analysis based on the inclusion and exclusion criteria. All of the included studies were retrospective observational cohorts. Elevated PLR predicted poor OS (HR: 1.38, 95% CI: 1.19-1.62, P < 0.001) and RFS or PFS (HR = 1.55; 95% CI = 1.27-1.88; P < 0.001). Moreover, elevated PLR was highly associated with male sex (male versus female OR = 0.59, 95% CI: 0.44-0.80, P < 0.001) and R1 resection margin (OR = 2.09, 95% CI: 1.24-3.54, P = 0.006). CONCLUSION: The present meta-analysis demonstrated that pretreatment PLR might serve as a useful prognostic biomarker in cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"proteomic identification potential clonorchis sinensis excretory secretory products capable binding activating human hepatic stellate cells epidemiological experimental evidence demonstrated clonorchis sinensis important risk factor hepatic fibrosis cholangiocarcinoma c sinensis excretory secretory products csesps protein complex including proteases antioxidant enzymes metabolic enzymes may contribute pathogenesis liver fluke associated hepatobiliary diseases however potential csesp candidates involved hepatic fibrosis cholangiocarcinoma still remain elucidated present study performed proteomic identification csesp candidates capable binding activating human hepatic stellate cell line lx 2 immunofluorescence analysis confirmed interaction csesps lx 2 cell membrane lx 2 cells stimulated csesps 24 h post incubation p 0 05 specifically 50 g ml csesps showed strongest effect cell proliferation methyl thiazolyl tetrazolium mtt assay also demonstrated flow cytometry analysis p 0 01 furthermore expression level human type iii collagen lx 2 cells treated csesps significantly higher control cells measured molecular beacon semiquantitative reverse transcription rt pcr approaches p 0 01 finally csesps incubation lx 2 cells subjected two dimensional gel electrophoresis 2 de analysis matrix associated laser desorption ionization time flight maldi tof mass spectrometry analysis nine proteins abundance change threefold rho gtpase activating protein mitochondrial cytochrome c oxidase subunit va enolase phospholipase c interleukin 15 insect derived growth factor cytochrome c oxidase subunit vi dnah1 protein kinesin light chain taken together identified potential csesp candidates capable binding activating human hepatic stellate cells providing direct evidences previously unknown accelerate strategies c sinensis prevention stn","probabilities":0.9467213,"Title":"Proteomic Identification Of Potential Clonorchis Sinensis Excretory/Secretory Products Capable Of Binding And Activating Human Hepatic Stellate Cells","Abstract":"Epidemiological and experimental evidence demonstrated that Clonorchis sinensis is an important risk factor of hepatic fibrosis and cholangiocarcinoma. C. sinensis excretory/secretory products (CsESPs) are protein complex including proteases, antioxidant enzymes, and metabolic enzymes, which may contribute to pathogenesis of liver fluke-associated hepatobiliary diseases. However, potential CsESP candidates involved into hepatic fibrosis and cholangiocarcinoma still remain to be elucidated. In the present study, we performed proteomic identification of CsESP candidates capable of binding and activating human hepatic stellate cell line LX-2. Immunofluorescence analysis confirmed the interaction of CsESPs with LX-2 cell membrane. LX-2 cells could be stimulated by CsESPs from 24 h post incubation (p < 0.05). Specifically, 50 μg/ml of CsESPs showed the strongest effect on cell proliferation in methyl thiazolyl tetrazolium (MTT) assay which could also be demonstrated by flow cytometry analysis (p < 0.01). Furthermore, expression level of human type III collagen in LX-2 cells treated with CsESPs was significantly higher than that in control cells measured by molecular beacon and semiquantitative reverse transcription (RT)-PCR approaches (p < 0.01). Finally, CsESPs before and after incubation with LX-2 cells were subjected to two-dimensional gel electrophoresis (2-DE) analysis and matrix associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis. Nine proteins with abundance change above threefold were Rho GTPase-activating protein, mitochondrial cytochrome c oxidase subunit Va, α-enolase, phospholipase C, interleukin-15, insect-derived growth factor, cytochrome c oxidase subunit VI, DNAH1 protein, and kinesin light chain. Taken together, we identified potential CsESP candidates capable of binding and activating human hepatic stellate cells, providing more direct evidences that are previously unknown to accelerate strategies for C. sinensis prevention.","Source":"STN","category":"ANIMAL","training_data":"Proteomic Identification Of Potential Clonorchis Sinensis Excretory/Secretory Products Capable Of Binding And Activating Human Hepatic Stellate Cells Epidemiological and experimental evidence demonstrated that Clonorchis sinensis is an important risk factor of hepatic fibrosis and cholangiocarcinoma. C. sinensis excretory/secretory products (CsESPs) are protein complex including proteases, antioxidant enzymes, and metabolic enzymes, which may contribute to pathogenesis of liver fluke-associated hepatobiliary diseases. However, potential CsESP candidates involved into hepatic fibrosis and cholangiocarcinoma still remain to be elucidated. In the present study, we performed proteomic identification of CsESP candidates capable of binding and activating human hepatic stellate cell line LX-2. Immunofluorescence analysis confirmed the interaction of CsESPs with LX-2 cell membrane. LX-2 cells could be stimulated by CsESPs from 24 h post incubation (p < 0.05). Specifically, 50 μg/ml of CsESPs showed the strongest effect on cell proliferation in methyl thiazolyl tetrazolium (MTT) assay which could also be demonstrated by flow cytometry analysis (p < 0.01). Furthermore, expression level of human type III collagen in LX-2 cells treated with CsESPs was significantly higher than that in control cells measured by molecular beacon and semiquantitative reverse transcription (RT)-PCR approaches (p < 0.01). Finally, CsESPs before and after incubation with LX-2 cells were subjected to two-dimensional gel electrophoresis (2-DE) analysis and matrix associated laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry analysis. Nine proteins with abundance change above threefold were Rho GTPase-activating protein, mitochondrial cytochrome c oxidase subunit Va, α-enolase, phospholipase C, interleukin-15, insect-derived growth factor, cytochrome c oxidase subunit VI, DNAH1 protein, and kinesin light chain. Taken together, we identified potential CsESP candidates capable of binding and activating human hepatic stellate cells, providing more direct evidences that are previously unknown to accelerate strategies for C. sinensis prevention. STN","prediction_labels":"ANIMAL"},{"cleaned":"resection margin influences survival pancreatoduodenectomy distal cholangiocarcinoma introduction distal cholangiocarcinoma remains rare cancer associated dismal outcome lack effective treatment options disease amendable resection surgery affords best potential long term survival aim study examine survival outcomes prognostic factors patients undergoing pancreatoduodenectomy distal cholangiocarcinoma methods january 2004 may 2016 patients undergone pancreatoduodenectomy histologically proven distal cholangiocarcinoma identified clinicopathologic data survival outcomes reported results pancreatoduodenectomy alone performed 20 patients 71 eight patients 29 required concomitant vascular resection major complication rate 43 n 12 nineteen patients 68 node positive disease eighteen patients 64 r0 resection median survival 36 months 95 ci 9 7 63 8 5 year survival rate 24 univariate analysis identified asa p 0 001 tumor grade p 0 009 margin status p 0 042 prognostic factors associated survival conclusion long term survival may achieved selected patients undergoing pancreatoduodenectomy distal cholangiocarcinoma especially patients achieved r0 resection pubmed","probabilities":0.9799733,"Title":"Resection margin influences survival after pancreatoduodenectomy for distal cholangiocarcinoma","Abstract":"INTRODUCTION: Distal cholangiocarcinoma remains a rare cancer associated with a dismal outcome. There is a lack of effective treatment options and where disease is amendable to resection, surgery affords the best potential for long-term survival. The aim of this study was to examine the survival outcomes and prognostic factors of patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma. METHODS: Between January 2004 to May 2016, patients who had undergone pancreatoduodenectomy with histologically proven distal cholangiocarcinoma were identified. Clinicopathologic data and survival outcomes were reported. RESULTS: Pancreatoduodenectomy alone was performed in 20 patients (71%) and eight patients (29%) required concomitant vascular resection. The major complication rate was 43% (n = 12). Nineteen patients (68%) had node positive disease. Eighteen patients (64%) had R0 resection. The median survival was 36 months (95%CI 9.7 to 63.8) and 5-year survival rate was 24%. Univariate analysis identified ASA (P < 0.001), tumor grade (P = 0.009) and margin status (P = 0.042) as prognostic factors associated with survival. CONCLUSION: Long-term survival may be achieved in selected patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma, especially in patients who achieved an R0 resection.","Source":"PubMed","category":"HUMAN","training_data":"Resection margin influences survival after pancreatoduodenectomy for distal cholangiocarcinoma INTRODUCTION: Distal cholangiocarcinoma remains a rare cancer associated with a dismal outcome. There is a lack of effective treatment options and where disease is amendable to resection, surgery affords the best potential for long-term survival. The aim of this study was to examine the survival outcomes and prognostic factors of patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma. METHODS: Between January 2004 to May 2016, patients who had undergone pancreatoduodenectomy with histologically proven distal cholangiocarcinoma were identified. Clinicopathologic data and survival outcomes were reported. RESULTS: Pancreatoduodenectomy alone was performed in 20 patients (71%) and eight patients (29%) required concomitant vascular resection. The major complication rate was 43% (n = 12). Nineteen patients (68%) had node positive disease. Eighteen patients (64%) had R0 resection. The median survival was 36 months (95%CI 9.7 to 63.8) and 5-year survival rate was 24%. Univariate analysis identified ASA (P < 0.001), tumor grade (P = 0.009) and margin status (P = 0.042) as prognostic factors associated with survival. CONCLUSION: Long-term survival may be achieved in selected patients undergoing pancreatoduodenectomy for distal cholangiocarcinoma, especially in patients who achieved an R0 resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"combined pancreaticoduodenectomy colon resection locally advanced peri ampullary tumours analysis peri operative morbidity mortality background combined pancreaticoduodenectomy pd colonic resection may necessary achieve r0 resection peri ampullary tumours aim study examine morbidity mortality associated procedure methods retrospective cohort study performed comparing 607 patients underwent standard pancreaticoduodenectomy pd 28 patients concomitant colon resection pd pd colon 10 year period academic centre results patients pd colon group likely received neoadjuvant chemotherapy radiation 3 28 11 versus 14 607 2 p 0 024 operative time also longer 530 versus 410 min p 0 001 likely portal vein resections 9 28 32 versus 76 607 13 p 0 007 difference intra operative blood loss length stay overall complication rates pd colon group higher rate severe post operative bleeding 4 28 11 versus 8 607 1 p 0 002 post operative mortality rates pd colon pd groups 2 28 7 8 607 1 respectively p 0 068 conclusions pd colon acceptable risk peri operative morbidity compared pd well selected patients stn","probabilities":0.9799733,"Title":"Combined Pancreaticoduodenectomy And Colon Resection For Locally Advanced Peri-Ampullary Tumours: Analysis Of Peri-Operative Morbidity And Mortality","Abstract":"Background: Combined pancreaticoduodenectomy (PD) and colonic resection may be necessary to achieve an R0 resection of peri-ampullary tumours. The aim of this study was to examine the morbidity and mortality associated with this procedure. \r\n\r\n Methods: A retrospective cohort study was performed comparing 607 patients who underwent a standard pancreaticoduodenectomy (S-PD) to 28 patients who had a concomitant colon resection and PD (PD-colon) over a 10-year period at an academic centre. \r\n\r\n Results: Patients in the PD-colon group were more likely to have received neoadjuvant chemotherapy ± radiation (3/28, 11% versus 14/607, 2%, P = 0.024). Operative time was also longer (530 versus 410 min, P < 0.001) and they were more likely to have had portal vein resections (9/28, 32% versus 76/607, 13%, P = 0.007). There was no difference in the intra-operative blood loss, length of stay, or overall complication rates. The PD-colon group had a higher rate of severe post-operative bleeding (4/28, 11% versus 8/607, 1%, P = 0.002). The post-operative mortality rates for the PD-colon and PD groups were 2/28 (7%) and 8/607 (1%), respectively (P = 0.068). \r\n\r\n Conclusions: PD-colon has an acceptable risk of peri-operative morbidity compared with S-PD in well-selected patients.","Source":"STN","category":"HUMAN","training_data":"Combined Pancreaticoduodenectomy And Colon Resection For Locally Advanced Peri-Ampullary Tumours: Analysis Of Peri-Operative Morbidity And Mortality Background: Combined pancreaticoduodenectomy (PD) and colonic resection may be necessary to achieve an R0 resection of peri-ampullary tumours. The aim of this study was to examine the morbidity and mortality associated with this procedure. \r\n\r\n Methods: A retrospective cohort study was performed comparing 607 patients who underwent a standard pancreaticoduodenectomy (S-PD) to 28 patients who had a concomitant colon resection and PD (PD-colon) over a 10-year period at an academic centre. \r\n\r\n Results: Patients in the PD-colon group were more likely to have received neoadjuvant chemotherapy ± radiation (3/28, 11% versus 14/607, 2%, P = 0.024). Operative time was also longer (530 versus 410 min, P < 0.001) and they were more likely to have had portal vein resections (9/28, 32% versus 76/607, 13%, P = 0.007). There was no difference in the intra-operative blood loss, length of stay, or overall complication rates. The PD-colon group had a higher rate of severe post-operative bleeding (4/28, 11% versus 8/607, 1%, P = 0.002). The post-operative mortality rates for the PD-colon and PD groups were 2/28 (7%) and 8/607 (1%), respectively (P = 0.068). \r\n\r\n Conclusions: PD-colon has an acceptable risk of peri-operative morbidity compared with S-PD in well-selected patients. STN","prediction_labels":"HUMAN"},{"cleaned":"preoperative cholangitis metastatic lymph node negative impact survival resection extrahepatic bile duct cancer background significance presence preoperative inflammation prognosis patients extrahepatic bile duct cancer bdca evaluated methods clinical data 84 patients underwent surgery bdca august 2003 may 2009 reviewed survival analysis performed patients classified two groups according presence preoperative cholangitis group cholangitis n 59 group b cholangitis n 25 results differences sex mean age tnm stage biliary drainage type resection radicality two groups p 0 05 3 year disease specific survival dss disease free survival dfs rates group b patients 21 5 11 9 respectively significantly lower group patients 66 1 57 3 respectively p 0 013 0 001 respectively multivariate analysis showed preoperative inflammation lymph node metastasis independent prognostic factors overall survival os p 0 021 relative risk rr 2 224 p 0 015 rr 2 367 respectively dfs p 0 014 rr 2 192 p 0 013 rr 2 240 respectively rates angiolymphatic perineural invasion higher group b group p 0 016 0 030 respectively conclusions presence preoperative inflammation independent poor prognostic factor os dfs patients bdca stn","probabilities":0.9799733,"Title":"Preoperative Cholangitis And Metastatic Lymph Node Have A Negative Impact On Survival After Resection Of Extrahepatic Bile Duct Cancer","Abstract":"Background: The significance of the presence of preoperative inflammation for the prognosis of patients with extrahepatic bile duct cancer (BDCA) was evaluated. \n\n Methods: The clinical data of 84 patients who underwent surgery for BDCA from August 2003 to May 2009 were reviewed, and survival analysis was performed. The patients were classified into two groups according to the presence of preoperative cholangitis: Group A had no cholangitis (n = 59), and group B had cholangitis (n = 25). \n\n Results: There were no differences in sex, mean age, TNM stage, biliary drainage, type of resection, or radicality between the two groups (p > 0.05). The 3-year disease-specific survival (DSS) and disease-free survival (DFS) rates for the group B patients (21.5 and 11.9 %, respectively) were significantly lower than those for the group A patients (66.1 and 57.3 %, respectively; p = 0.013 and 0.001, respectively). The multivariate analysis showed that preoperative inflammation and lymph node metastasis were the independent prognostic factors for both overall survival (OS) [p = 0.021, relative risk (RR) = 2.224 and p = 0.015, RR = 2.367, respectively] and DFS (p = 0.014; RR = 2.192 and p = 0.013; RR = 2.240, respectively). The rates of angiolymphatic and perineural invasion were higher for group B than those for group A (p = 0.016 and 0.030, respectively). \n\n Conclusions: The presence of preoperative inflammation is an independent poor prognostic factor for OS and DFS for patients with BDCA.","Source":"STN","category":"HUMAN","training_data":"Preoperative Cholangitis And Metastatic Lymph Node Have A Negative Impact On Survival After Resection Of Extrahepatic Bile Duct Cancer Background: The significance of the presence of preoperative inflammation for the prognosis of patients with extrahepatic bile duct cancer (BDCA) was evaluated. \n\n Methods: The clinical data of 84 patients who underwent surgery for BDCA from August 2003 to May 2009 were reviewed, and survival analysis was performed. The patients were classified into two groups according to the presence of preoperative cholangitis: Group A had no cholangitis (n = 59), and group B had cholangitis (n = 25). \n\n Results: There were no differences in sex, mean age, TNM stage, biliary drainage, type of resection, or radicality between the two groups (p > 0.05). The 3-year disease-specific survival (DSS) and disease-free survival (DFS) rates for the group B patients (21.5 and 11.9 %, respectively) were significantly lower than those for the group A patients (66.1 and 57.3 %, respectively; p = 0.013 and 0.001, respectively). The multivariate analysis showed that preoperative inflammation and lymph node metastasis were the independent prognostic factors for both overall survival (OS) [p = 0.021, relative risk (RR) = 2.224 and p = 0.015, RR = 2.367, respectively] and DFS (p = 0.014; RR = 2.192 and p = 0.013; RR = 2.240, respectively). The rates of angiolymphatic and perineural invasion were higher for group B than those for group A (p = 0.016 and 0.030, respectively). \n\n Conclusions: The presence of preoperative inflammation is an independent poor prognostic factor for OS and DFS for patients with BDCA. STN","prediction_labels":"HUMAN"},{"cleaned":"silencing lamc2 reverses epithelial mesenchymal transition inhibits angiogenesis cholangiocarcinoma via inactivation epidermal growth factor receptor signaling pathway cholangiocarcinoma cca malignant cancer associated high mortality rates relationship laminin 2 chain gene lamc2 epidermal growth factor receptor egfr previously documented gastric cancer oral squamous cell carcinoma study investigates role lamc2 epithelial mesenchymal transition emt angiogenesis cca explores underlying mechanism differentially expressed genes related cca initially screened using microarray analysis interaction lamc2 egfr signaling pathway identified determine regulatory effects lamc2 cca progression lamc2 silenced overexpressed egfr signaling pathway activated blocked subsequently regulation effects lamc2 evaluated expression emt markers invasion migration cca cells well microvessel density nude mice microarray analysis demonstrated highly expressed lamc2 linked cca development involves egfr signaling pathway lamc2 expression increased egfr signaling pathway emt activated cca tissues silencing lamc2 well egfr signaling pathway inhibition led suppression emt cell invasion migration abilities vitro well angiogenesis vivo study demonstrates lamc2 silencing suppresses activity egfr signaling pathway thus functioning tumor suppressor cca stn","probabilities":0.9467213,"Title":"Silencing Of Lamc2 Reverses Epithelial-Mesenchymal Transition And Inhibits Angiogenesis In Cholangiocarcinoma Via Inactivation Of The Epidermal Growth Factor Receptor Signaling Pathway","Abstract":"Cholangiocarcinoma (CCA) is a malignant cancer that is associated with high mortality rates. The relationship between laminin γ 2 chain gene (LAMC2) and epidermal growth factor receptor (EGFR) has been previously documented in gastric cancer and oral squamous cell carcinoma. This study investigates the role of LAMC2 in epithelial-mesenchymal transition (EMT) and angiogenesis in CCA and explores the underlying mechanism(s). Differentially expressed genes related to CCA were initially screened using a microarray analysis, and the interaction between LAMC2 and the EGFR signaling pathway was identified. To determine the regulatory effects of LAMC2 on CCA progression, LAMC2 was silenced or overexpressed and the EGFR signaling pathway was activated or blocked. Subsequently, the regulation effects of LAMC2 were evaluated on the expression of EMT markers, invasion and migration of CCA cells, as well as microvessel density in nude mice. Microarray analysis demonstrated that highly expressed LAMC2 is linked to CCA development, which involves the EGFR signaling pathway. When LAMC2 expression was increased, the EGFR signaling pathway and EMT were activated in CCA tissues. Silencing of LAMC2 as well as EGFR signaling pathway inhibition led to suppression of EMT, cell invasion, and migration abilities in vitro, as well as angiogenesis in vivo. This study demonstrates that LAMC2 silencing suppresses the activity of the EGFR signaling pathway, thus functioning as a tumor suppressor in CCA.","Source":"STN","category":"ANIMAL","training_data":"Silencing Of Lamc2 Reverses Epithelial-Mesenchymal Transition And Inhibits Angiogenesis In Cholangiocarcinoma Via Inactivation Of The Epidermal Growth Factor Receptor Signaling Pathway Cholangiocarcinoma (CCA) is a malignant cancer that is associated with high mortality rates. The relationship between laminin γ 2 chain gene (LAMC2) and epidermal growth factor receptor (EGFR) has been previously documented in gastric cancer and oral squamous cell carcinoma. This study investigates the role of LAMC2 in epithelial-mesenchymal transition (EMT) and angiogenesis in CCA and explores the underlying mechanism(s). Differentially expressed genes related to CCA were initially screened using a microarray analysis, and the interaction between LAMC2 and the EGFR signaling pathway was identified. To determine the regulatory effects of LAMC2 on CCA progression, LAMC2 was silenced or overexpressed and the EGFR signaling pathway was activated or blocked. Subsequently, the regulation effects of LAMC2 were evaluated on the expression of EMT markers, invasion and migration of CCA cells, as well as microvessel density in nude mice. Microarray analysis demonstrated that highly expressed LAMC2 is linked to CCA development, which involves the EGFR signaling pathway. When LAMC2 expression was increased, the EGFR signaling pathway and EMT were activated in CCA tissues. Silencing of LAMC2 as well as EGFR signaling pathway inhibition led to suppression of EMT, cell invasion, and migration abilities in vitro, as well as angiogenesis in vivo. This study demonstrates that LAMC2 silencing suppresses the activity of the EGFR signaling pathway, thus functioning as a tumor suppressor in CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"identification bile biomarkers biliary tract cancer liquid chromatography mass spectrometry based metabolomic method incidence mortality rate biliary tract cancer increasing worldwide however diagnosis prognosis improved recent years novel approach termed metabolomics may potential developed effective diagnostic tool present study prospectively obtained bile samples 115 individuals including 32 patients biliary tract cancer 61 patients benign biliary tract diseases 22 normal controls liquid chromatography mass spectrometry lc ms based approach used investigate differences bile samples three groups followed multivariate statistical analysis included partial least squares projection latent structures discriminant analysis pls da orthogonal projection latent structures discriminant analysis opls da metabolomic 2d score plot 3d plot revealed clear separation cancer benign normal control groups pls da address significant difficulties clinically differentiating biliary tract cancer benign biliary tract diseases opls da performed distinguish two disease groups select potential biomarkers cancer benign groups well differentiated metabolic analysis revealed significantly lower levels lysophosphatidylcholine phenylalanine 2 octenoylcarnitine tryptophan significantly higher levels taurine glycine conjugated bile acids bile patients biliary tract cancer compared bile patients benign biliary tract disease present study suggested lc ms based metabolomic investigation provides potent promising approach discriminating biliary tract cancer benign biliary tract diseases identified specific metabolites may offer potential novel biomarkers early detection biliary tract cancer pubmed","probabilities":0.9799733,"Title":"Identification of bile biomarkers of biliary tract cancer through a liquid chromatography/mass spectrometry-based metabolomic method","Abstract":"The incidence and mortality rate of biliary tract cancer have been increasing worldwide; however, its diagnosis and prognosis have not improved in recent years. A novel approach, termed 'metabolomics', may have the potential to be developed as an effective diagnostic tool. The present study prospectively obtained bile samples from 115 individuals, including 32 patients with biliary tract cancer, 61 patients with benign biliary tract diseases and 22 normal controls. A liquid chromatography/mass spectrometry (LC/MS)‑based approach was used to investigate the differences in bile samples between the three groups, followed by multivariate statistical analysis, which included partial least squares projection to latent structures with discriminant analysis (PLS‑DA) and orthogonal projection to latent structures with discriminant analysis (OPLS‑DA). The metabolomic 2D score plot and 3D plot revealed clear separation between the cancer, benign and normal control groups by PLS‑DA. To further address the significant difficulties in clinically differentiating between biliary tract cancer and benign biliary tract diseases, OPLS‑DA was performed to distinguish between the two disease groups and to select potential biomarkers. The cancer and benign groups were well differentiated. The metabolic analysis revealed significantly lower levels of lysophosphatidylcholine, phenylalanine, 2‑octenoylcarnitine, tryptophan and significantly higher levels of taurine‑ and glycine‑conjugated bile acids in the bile from patients with biliary tract cancer compared with those in the bile from patients with benign biliary tract disease. The present study suggested that an LC/MS‑based metabolomic investigation provides a potent and promising approach for discriminating biliary tract cancer from benign biliary tract diseases and the identified specific metabolites may offer potential as novel biomarkers for the early detection of biliary tract cancer.","Source":"PubMed","category":"HUMAN","training_data":"Identification of bile biomarkers of biliary tract cancer through a liquid chromatography/mass spectrometry-based metabolomic method The incidence and mortality rate of biliary tract cancer have been increasing worldwide; however, its diagnosis and prognosis have not improved in recent years. A novel approach, termed 'metabolomics', may have the potential to be developed as an effective diagnostic tool. The present study prospectively obtained bile samples from 115 individuals, including 32 patients with biliary tract cancer, 61 patients with benign biliary tract diseases and 22 normal controls. A liquid chromatography/mass spectrometry (LC/MS)‑based approach was used to investigate the differences in bile samples between the three groups, followed by multivariate statistical analysis, which included partial least squares projection to latent structures with discriminant analysis (PLS‑DA) and orthogonal projection to latent structures with discriminant analysis (OPLS‑DA). The metabolomic 2D score plot and 3D plot revealed clear separation between the cancer, benign and normal control groups by PLS‑DA. To further address the significant difficulties in clinically differentiating between biliary tract cancer and benign biliary tract diseases, OPLS‑DA was performed to distinguish between the two disease groups and to select potential biomarkers. The cancer and benign groups were well differentiated. The metabolic analysis revealed significantly lower levels of lysophosphatidylcholine, phenylalanine, 2‑octenoylcarnitine, tryptophan and significantly higher levels of taurine‑ and glycine‑conjugated bile acids in the bile from patients with biliary tract cancer compared with those in the bile from patients with benign biliary tract disease. The present study suggested that an LC/MS‑based metabolomic investigation provides a potent and promising approach for discriminating biliary tract cancer from benign biliary tract diseases and the identified specific metabolites may offer potential as novel biomarkers for the early detection of biliary tract cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathologic analysis prognostic factors survival early stage patients ampullary carcinoma clinicopathologic findings clinical follow data 31 patients non icteric ampullary carcinoma niac 111 patients icteric ampullary carcinoma iac retrospectively compared iac patients presented obstructive jaundice twenty three 31 niac patients developed abdominal pain fever caused cholangitis pancreatitis remaining eight patients asymptomatic two groups significantly different age sex size tumor macroscopic type lymph node metastasis perineural invasion lymphatic permeation venous invasion eighteen 31 niacs 58 stages ii whereas 25 111 iacs 22 stages ii p less 0 01 seventeen 31 niacs 55 papillary adenocarcinoma compared 39 111 iacs 35 p less 0 05 involvement biliary tract niac showed intraluminal papillary growth 14 cases 45 whereas iac showed periductal invasion 58 cases 52 p less 0 05 cumulative 5 yr 10 yr survival rates 31 patients niac 57 57 compared 32 23 105 patients iac p less 0 05 p less 0 01 survival curve niac significantly better iac p less 0 01 non icteric presentation independent prognostic value determined multivariate regression analysis niac fares better iac niac includes greater number early ampullary carcinoma papillary adenocarcinoma detection niac may therefore product improvement clinical course ampullary carcinoma stn","probabilities":0.9799733,"Title":"Clinicopathologic Analysis And Prognostic Factors For Survival In Early Stage Patients With Ampullary Carcinoma","Abstract":"Clinicopathologic findings and clinical follow-up data of 31 patients with non-icteric ampullary carcinoma (NIAC) and 111 patients with icteric ampullary carcinoma (IAC) were retrospectively compared. All of the IAC patients presented with obstructive jaundice. Twenty-three of the 31 NIAC patients developed abdominal pain and/or fever caused by cholangitis or pancreatitis, and the remaining eight patients were asymptomatic. The two groups were not significantly different in age, sex, size of the tumor, macroscopic type, lymph node metastasis, perineural invasion, lymphatic permeation, and venous invasion. Eighteen of the 31 NIACs (58%) were in stages I and II, whereas 25 of the 111 IACs (22%) were in stages I and II (p less than 0.01). Seventeen of the 31 NIACs (55%) were papillary adenocarcinoma, compared with 39 of 111 IACs (35%) (p less than 0.05). As to involvement of the biliary tract, the NIAC showed an intraluminal papillary growth in 14 cases (45%), whereas the IAC showed a periductal invasion in 58 cases (52%) (p less than 0.05). The cumulative 5-yr and 10-yr survival rates of 31 patients with NIAC were 57% and 57%, compared with 32% and 23% of 105 patients with IAC (p less than 0.05; p less than 0.01). The survival curve of the NIAC was significantly better than that of the IAC (p less than 0.01). Non-icteric presentation had no independent prognostic value, as determined by multivariate regression analysis. The NIAC fares better than the IAC, because the NIAC includes a greater number of early ampullary carcinoma and papillary adenocarcinoma. The detection of NIAC may therefore product an improvement in the clinical course of ampullary carcinoma.","Source":"STN","category":"HUMAN","training_data":"Clinicopathologic Analysis And Prognostic Factors For Survival In Early Stage Patients With Ampullary Carcinoma Clinicopathologic findings and clinical follow-up data of 31 patients with non-icteric ampullary carcinoma (NIAC) and 111 patients with icteric ampullary carcinoma (IAC) were retrospectively compared. All of the IAC patients presented with obstructive jaundice. Twenty-three of the 31 NIAC patients developed abdominal pain and/or fever caused by cholangitis or pancreatitis, and the remaining eight patients were asymptomatic. The two groups were not significantly different in age, sex, size of the tumor, macroscopic type, lymph node metastasis, perineural invasion, lymphatic permeation, and venous invasion. Eighteen of the 31 NIACs (58%) were in stages I and II, whereas 25 of the 111 IACs (22%) were in stages I and II (p less than 0.01). Seventeen of the 31 NIACs (55%) were papillary adenocarcinoma, compared with 39 of 111 IACs (35%) (p less than 0.05). As to involvement of the biliary tract, the NIAC showed an intraluminal papillary growth in 14 cases (45%), whereas the IAC showed a periductal invasion in 58 cases (52%) (p less than 0.05). The cumulative 5-yr and 10-yr survival rates of 31 patients with NIAC were 57% and 57%, compared with 32% and 23% of 105 patients with IAC (p less than 0.05; p less than 0.01). The survival curve of the NIAC was significantly better than that of the IAC (p less than 0.01). Non-icteric presentation had no independent prognostic value, as determined by multivariate regression analysis. The NIAC fares better than the IAC, because the NIAC includes a greater number of early ampullary carcinoma and papillary adenocarcinoma. The detection of NIAC may therefore product an improvement in the clinical course of ampullary carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"impact residual situ carcinoma postoperative survival 125 patients extrahepatic bile duct carcinoma purpose aim study determine impact presence carcinoma situ bile duct stump postoperative survival patients underwent resection extrahepatic bile duct carcinoma methods patients resected extrahepatic bile duct carcinoma divided three groups according resected margin status evidence residual carcinoma negative group n 96 carcinoma situ bile duct stump cis group n 10 invasive carcinoma surgical margin invasive group n 19 cause specific survival groups compared statistically results surgical margin status identified prognostic factor univariate analysis p 0 005 independent prognostic factor multivariate analysis p 0 018 cis group displayed significantly better survival invasive group p 0 006 survival comparable negative group p 0 533 two three patients cis group local recurrence died 5 years surgical resection conclusions patients positive ductal margins carcinoma situ extrahepatic bile duct appear show different survival resection compared patients negative margins remnant carcinoma situ likely develop late local recurrence stn","probabilities":0.9799733,"Title":"Impact Of Residual In Situ Carcinoma On Postoperative Survival In 125 Patients With Extrahepatic Bile Duct Carcinoma","Abstract":"Purpose: The aim of this study was to determine the impact of the presence of carcinoma in situ at the bile duct stump on postoperative survival in patients who underwent resection of extrahepatic bile duct carcinoma. \r\n\r\n Methods: The patients with resected extrahepatic bile duct carcinoma were divided into three groups according to resected margin status: no evidence of residual carcinoma (Negative group, n = 96); carcinoma in situ at the bile duct stump (CIS group, n = 10); and invasive carcinoma at any surgical margin (Invasive group, n = 19). Cause-specific survival for these groups was compared statistically. \r\n\r\n Results: Surgical margin status was identified as a prognostic factor on univariate analysis (p = 0.005) and was an independent prognostic factor on multivariate analysis (p = 0.018). The CIS group displayed significantly better survival than the Invasive group (p = 0.006), and the survival was comparable to that for the Negative group (p = 0.533). Two of three patients in the CIS group with local recurrence died >5 years after surgical resection. \r\n\r\n Conclusions: Patients with positive ductal margins of carcinoma in situ of the extrahepatic bile duct do not appear to show different survival after resection compared to patients with negative margins, but remnant carcinoma in situ is likely to develop late local recurrence.","Source":"STN","category":"HUMAN","training_data":"Impact Of Residual In Situ Carcinoma On Postoperative Survival In 125 Patients With Extrahepatic Bile Duct Carcinoma Purpose: The aim of this study was to determine the impact of the presence of carcinoma in situ at the bile duct stump on postoperative survival in patients who underwent resection of extrahepatic bile duct carcinoma. \r\n\r\n Methods: The patients with resected extrahepatic bile duct carcinoma were divided into three groups according to resected margin status: no evidence of residual carcinoma (Negative group, n = 96); carcinoma in situ at the bile duct stump (CIS group, n = 10); and invasive carcinoma at any surgical margin (Invasive group, n = 19). Cause-specific survival for these groups was compared statistically. \r\n\r\n Results: Surgical margin status was identified as a prognostic factor on univariate analysis (p = 0.005) and was an independent prognostic factor on multivariate analysis (p = 0.018). The CIS group displayed significantly better survival than the Invasive group (p = 0.006), and the survival was comparable to that for the Negative group (p = 0.533). Two of three patients in the CIS group with local recurrence died >5 years after surgical resection. \r\n\r\n Conclusions: Patients with positive ductal margins of carcinoma in situ of the extrahepatic bile duct do not appear to show different survival after resection compared to patients with negative margins, but remnant carcinoma in situ is likely to develop late local recurrence. STN","prediction_labels":"HUMAN"},{"cleaned":"cdk7 inhibitor thz1 inhibits mcl1 synthesis drives cholangiocarcinoma apoptosis combination bcl2 bcl xl inhibitor abt 263 cholangiocarcinoma cca fatal disease without effective targeted therapy screened small molecule library 116 inhibitors targeting different targets cell cycle discovered several kinases including cyclin dependent kinase 7 cdk7 vulnerabilities cca analysis multiple cca data sets demonstrated cdk7 overexpressed cca tissues studies demonstrated cdk7 inhibitor thz1 inhibited cell viability induced apoptosis cca cells also showed thz1 inhibited cca cell growth xenograft model rna sequencing followed gene ontology analysis showed striking impact thz1 dna templated transcriptional programs thz1 downregulated cdk7 mediated phosphorylation rna polymerase ii indicative transcriptional inhibition number oncogenic transcription factors survival proteins like mcl1 fosl1 runx1 repressed thz1 mcl1 one antiapoptotic bcl2 family members significantly inhibited upon thz1 treatment accordingly combining thz1 bcl2 bcl xl inhibitor abt 263 synergized impairing cell growth driving apoptosis results demonstrate cdk7 potential target treating cca combinations cdk7 inhibition bcl2 bcl xl inhibition may offer novel therapeutic strategy cca stn","probabilities":0.9467213,"Title":"Cdk7 Inhibitor Thz1 Inhibits Mcl1 Synthesis And Drives Cholangiocarcinoma Apoptosis In Combination With Bcl2/Bcl-Xl Inhibitor Abt-263","Abstract":"Cholangiocarcinoma (CCA) is a fatal disease without effective targeted therapy. We screened a small-molecule library of 116 inhibitors targeting different targets of the cell cycle and discovered several kinases, including Cyclin-dependent kinase 7 (CDK7) as vulnerabilities in CCA. Analysis of multiple CCA data sets demonstrated that CDK7 was overexpressed in CCA tissues. Further studies demonstrated that CDK7 inhibitor THZ1 inhibited cell viability and induced apoptosis in CCA cells. We also showed that THZ1 inhibited CCA cell growth in a xenograft model. RNA-sequencing followed by Gene ontology analysis showed a striking impact of THZ1 on DNA-templated transcriptional programs. THZ1 downregulated CDK7-mediated phosphorylation of RNA polymerase II, indicative of transcriptional inhibition. A number of oncogenic transcription factors and survival proteins, like MCL1, FOSL1, and RUNX1, were repressed by THZ1. MCL1, one of the antiapoptotic BCL2 family members, was significantly inhibited upon THZ1 treatment. Accordingly, combining THZ1 with a BCL2/BCL-XL inhibitor ABT-263 synergized in impairing cell growth and driving apoptosis. Our results demonstrate CDK7 as a potential target in treating CCA. Combinations of CDK7 inhibition and BCL2/BCL-XL inhibition may offer a novel therapeutic strategy for CCA.","Source":"STN","category":"ANIMAL","training_data":"Cdk7 Inhibitor Thz1 Inhibits Mcl1 Synthesis And Drives Cholangiocarcinoma Apoptosis In Combination With Bcl2/Bcl-Xl Inhibitor Abt-263 Cholangiocarcinoma (CCA) is a fatal disease without effective targeted therapy. We screened a small-molecule library of 116 inhibitors targeting different targets of the cell cycle and discovered several kinases, including Cyclin-dependent kinase 7 (CDK7) as vulnerabilities in CCA. Analysis of multiple CCA data sets demonstrated that CDK7 was overexpressed in CCA tissues. Further studies demonstrated that CDK7 inhibitor THZ1 inhibited cell viability and induced apoptosis in CCA cells. We also showed that THZ1 inhibited CCA cell growth in a xenograft model. RNA-sequencing followed by Gene ontology analysis showed a striking impact of THZ1 on DNA-templated transcriptional programs. THZ1 downregulated CDK7-mediated phosphorylation of RNA polymerase II, indicative of transcriptional inhibition. A number of oncogenic transcription factors and survival proteins, like MCL1, FOSL1, and RUNX1, were repressed by THZ1. MCL1, one of the antiapoptotic BCL2 family members, was significantly inhibited upon THZ1 treatment. Accordingly, combining THZ1 with a BCL2/BCL-XL inhibitor ABT-263 synergized in impairing cell growth and driving apoptosis. Our results demonstrate CDK7 as a potential target in treating CCA. Combinations of CDK7 inhibition and BCL2/BCL-XL inhibition may offer a novel therapeutic strategy for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"burden digestive diseases portugal trends hospitalizations 2000 2010 objective data burden gastrointestinal diseases incomplete particularly southern european countries aim study estimate burden digestive diseases portugal patients methods retrospective observational study based national hospitalizations database identified consecutive episodes first diagnosis digestive disease 2000 2010 using icd 9 cm codes comparative analyses carried assess hospitalization trends major indicators time across regions results 75 000 deaths attributable digestive diseases observed representing 16 overall hospital mortality half 59 premature deaths patients 75 years age biliary tract disease common digestive disorder leading hospitalization 249 817 episodes 5210 episodes acute stone related cholecystitis 2010 11 increase compared 2000 gastric cancer responsible highest number hospital deaths 10 278 alcohol related liver disorders accounted highest hospital premature deaths 7572 costs hospital mortality rate major digestive diseases showed significant positive relation progression time 0 195 p 0 001 however adjusted age significant significant positive associations found age hospital mortality odds ratio 1 032 p 0 001 costs hospital mortality odds ratio 1 054 p 0 001 conclusion portugal digestive diseases represent major burden evidence increasing trend ageing population contributes strongly towards increase placing demands healthcare organizations diseases gastric cancer biliary tract disease alcohol related liver disorders may require particular attention pubmed","probabilities":0.9799733,"Title":"Burden of digestive diseases in Portugal: trends in hospitalizations between 2000 and 2010","Abstract":"OBJECTIVE: Data on the burden of gastrointestinal diseases are incomplete, particularly in Southern European countries. The aim of this study was to estimate the burden of digestive diseases in Portugal. PATIENTS AND METHODS: This was a retrospective observational study based on the national hospitalizations database that identified all consecutive episodes with a first diagnosis of a digestive disease between 2000 and 2010 using ICD-9-CM codes. Comparative analyses were carried out to assess hospitalization trends of major indicators over time and across regions. RESULTS: More than 75,000 deaths attributable to digestive diseases were observed, representing 16% of the overall in-hospital mortality. Over half of these (59%) were premature deaths (in patients <75 years of age). Biliary tract disease was the most common digestive disorder leading to hospitalization (249,817 episodes, 5210 episodes of acute stone-related cholecystitis in 2010, with an 11% increase compared with 2000). Gastric cancer was responsible for the highest number of in-hospital deaths (10,278) and alcohol-related liver disorders accounted for the highest in-hospital premature deaths (7572). Both costs and the in-hospital mortality rate for major digestive diseases showed a significant positive relation with progression of time (β=0.195, P<0.001); however, when adjusted for age, this was not significant. Significant positive associations were found between age and in-hospital mortality (odds ratio=1.032, P<0.001) and between costs and in-hospital mortality (odds ratio=1.054, P<0.001). CONCLUSION: In Portugal, digestive diseases represent a major burden, with evidence of an increasing trend. An ageing population contributes strongly towards this increase, placing further demands on healthcare organizations. Diseases such as gastric cancer, biliary tract disease and alcohol-related liver disorders may require particular attention.","Source":"PubMed","category":"HUMAN","training_data":"Burden of digestive diseases in Portugal: trends in hospitalizations between 2000 and 2010 OBJECTIVE: Data on the burden of gastrointestinal diseases are incomplete, particularly in Southern European countries. The aim of this study was to estimate the burden of digestive diseases in Portugal. PATIENTS AND METHODS: This was a retrospective observational study based on the national hospitalizations database that identified all consecutive episodes with a first diagnosis of a digestive disease between 2000 and 2010 using ICD-9-CM codes. Comparative analyses were carried out to assess hospitalization trends of major indicators over time and across regions. RESULTS: More than 75,000 deaths attributable to digestive diseases were observed, representing 16% of the overall in-hospital mortality. Over half of these (59%) were premature deaths (in patients <75 years of age). Biliary tract disease was the most common digestive disorder leading to hospitalization (249,817 episodes, 5210 episodes of acute stone-related cholecystitis in 2010, with an 11% increase compared with 2000). Gastric cancer was responsible for the highest number of in-hospital deaths (10,278) and alcohol-related liver disorders accounted for the highest in-hospital premature deaths (7572). Both costs and the in-hospital mortality rate for major digestive diseases showed a significant positive relation with progression of time (β=0.195, P<0.001); however, when adjusted for age, this was not significant. Significant positive associations were found between age and in-hospital mortality (odds ratio=1.032, P<0.001) and between costs and in-hospital mortality (odds ratio=1.054, P<0.001). CONCLUSION: In Portugal, digestive diseases represent a major burden, with evidence of an increasing trend. An ageing population contributes strongly towards this increase, placing further demands on healthcare organizations. Diseases such as gastric cancer, biliary tract disease and alcohol-related liver disorders may require particular attention. PubMed","prediction_labels":"HUMAN"},{"cleaned":"molecular targets biliary carcinogenesis implications therapy biliary tract cancers btcs encompass group invasive carcinomas including cholangiocarcinoma intrahepatic perihilar extrahepatic gallbladder carcinoma approximately 90 patients present advanced unresectable disease poor prognosis latest recommendation treat advanced metastatic disease gemcitabine cisplatin although chemotherapy recorded modest survival benefits comprehension molecular basis biliary carcinogenesis resulted experimental trials targeted therapies btcs promising results review addresses emerging role targeted therapy treatment btcs findings preclinical studies reviewed correlated outcomes clinical trials undertaken translate laboratory discoveries implications practice biliary tract cancers rare approximately 90 patients present advanced unresectable disease poor prognosis median overall progression free survival 12 8 months respectively chemotherapy recorded modest survival benefits targeted therapies explored personalized treatment cancers comprehensive review targeted therapies biliary tract cancers undertaken present emerging evidence laboratory molecular studies translate clinical trials outcomes latest evidence topic presented clinicians practitioners guide decisions treatment disease pubmed","probabilities":0.9799733,"Title":"Molecular Targets in Biliary Carcinogenesis and Implications for Therapy","Abstract":"Biliary tract cancers (BTCs) encompass a group of invasive carcinomas, including cholangiocarcinoma (intrahepatic, perihilar, or extrahepatic), and gallbladder carcinoma. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. The latest recommendation is to treat advanced or metastatic disease with gemcitabine and cisplatin, although chemotherapy has recorded modest survival benefits. Comprehension of the molecular basis of biliary carcinogenesis has resulted in experimental trials of targeted therapies in BTCs, with promising results. This review addresses the emerging role of targeted therapy in the treatment of BTCs. Findings from preclinical studies were reviewed and correlated with the outcomes of clinical trials that were undertaken to translate the laboratory discoveries. IMPLICATIONS FOR PRACTICE: Biliary tract cancers are rare. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. Median overall and progression-free survival are 12 and 8 months, respectively. Because chemotherapy has recorded modest survival benefits, targeted therapies are being explored for personalized treatment of these cancers. A comprehensive review of targeted therapies in biliary tract cancers was undertaken to present emerging evidence from laboratory and/or molecular studies as they translate to clinical trials and outcomes. The latest evidence on this topic is presented to clinicians and practitioners to guide decisions on treatment of this disease.","Source":"PubMed","category":"HUMAN","training_data":"Molecular Targets in Biliary Carcinogenesis and Implications for Therapy Biliary tract cancers (BTCs) encompass a group of invasive carcinomas, including cholangiocarcinoma (intrahepatic, perihilar, or extrahepatic), and gallbladder carcinoma. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. The latest recommendation is to treat advanced or metastatic disease with gemcitabine and cisplatin, although chemotherapy has recorded modest survival benefits. Comprehension of the molecular basis of biliary carcinogenesis has resulted in experimental trials of targeted therapies in BTCs, with promising results. This review addresses the emerging role of targeted therapy in the treatment of BTCs. Findings from preclinical studies were reviewed and correlated with the outcomes of clinical trials that were undertaken to translate the laboratory discoveries. IMPLICATIONS FOR PRACTICE: Biliary tract cancers are rare. Approximately 90% of patients present with advanced, unresectable disease and have a poor prognosis. Median overall and progression-free survival are 12 and 8 months, respectively. Because chemotherapy has recorded modest survival benefits, targeted therapies are being explored for personalized treatment of these cancers. A comprehensive review of targeted therapies in biliary tract cancers was undertaken to present emerging evidence from laboratory and/or molecular studies as they translate to clinical trials and outcomes. The latest evidence on this topic is presented to clinicians and practitioners to guide decisions on treatment of this disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"serum cea ca125 ca19 9 ca724 levels diagnosis staging cholangiocarcinoma background aims serum markers provide non invasive cheap effective diagnostic prognostic tool cholangiocarcinoma study aimed evaluate serum levels cea ca125 ca19 9 ca724 diagnosis staging cholangiocarcinoma materials methods serum levels ca125 ca19 9 ca724 cea measured preoperatively postoperatively follow 153 cases cholangiocarcinoma 65 cases benign biliary disease results serum levels tumor markers elevated cholangiocarcinoma ca19 9 better cea ca125 ca724 combination diagnose cholangiocarcinoma cut value 73 25 u ml sensitivity 69 30 specificity 87 7 serum ca125 ca19 9 levels helpful assess advanced tnm stage conclusion serum ca19 9 level superior cea ca125 ca724 levels combination diagnosis cholangiocarcinoma preoperative serum levels ca19 9 used predict advanced tnm stage evaluate resectability cholangiocarcinoma google scholar","probabilities":0.9799733,"Title":"Serum Cea Ca125 Ca19-9 And Ca724 Levels For The Diagnosis And Staging Of Cholangiocarcinoma","Abstract":"Background: Aims serum markers provide a non-invasive, cheap and effective diagnostic and prognostic tool for cholangiocarcinoma. In this study, we aimed to evaluate serum levels of CEA, CA125, CA19-9 and CA724 for the diagnosis and staging of cholangiocarcinoma.\n\nMaterials and Methods: Serum levels of CA125, CA19-9, CA724 and CEA were measured preoperatively, postoperatively and during follow-up in 153 cases of cholangiocarcinoma and 65 cases of benign biliary disease.\n\nResults: Serum levels of these tumor markers elevated in cholangiocarcinoma, and CA19-9 was better than CEA, CA125, CA724 or the combination to diagnose cholangiocarcinoma with the cut off value of 73.25 U/ml (sensitivity 69.30%; specificity 87.7%). Serum CA125 and CA19-9 levels were helpful to assess advanced TNM stage.\n\nConclusion: Serum CA19-9 level is superior to CEA, CA125 or CA724 levels or the combination for the diagnosis of cholangiocarcinoma. Preoperative serum levels of CA19-9 could be used to predict advanced TNM stage and evaluate the resectability of cholangiocarcinoma.","Source":"Google Scholar","category":"HUMAN","training_data":"Serum Cea Ca125 Ca19-9 And Ca724 Levels For The Diagnosis And Staging Of Cholangiocarcinoma Background: Aims serum markers provide a non-invasive, cheap and effective diagnostic and prognostic tool for cholangiocarcinoma. In this study, we aimed to evaluate serum levels of CEA, CA125, CA19-9 and CA724 for the diagnosis and staging of cholangiocarcinoma.\n\nMaterials and Methods: Serum levels of CA125, CA19-9, CA724 and CEA were measured preoperatively, postoperatively and during follow-up in 153 cases of cholangiocarcinoma and 65 cases of benign biliary disease.\n\nResults: Serum levels of these tumor markers elevated in cholangiocarcinoma, and CA19-9 was better than CEA, CA125, CA724 or the combination to diagnose cholangiocarcinoma with the cut off value of 73.25 U/ml (sensitivity 69.30%; specificity 87.7%). Serum CA125 and CA19-9 levels were helpful to assess advanced TNM stage.\n\nConclusion: Serum CA19-9 level is superior to CEA, CA125 or CA724 levels or the combination for the diagnosis of cholangiocarcinoma. Preoperative serum levels of CA19-9 could be used to predict advanced TNM stage and evaluate the resectability of cholangiocarcinoma. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer presenting jaundice uniformly fatal still potentially curable background jaundice presenting symptom gallbladder cancer traditionally considered sign advanced disease inoperability poor outcome however recent studies demonstrated small subset patients undergo resection curative intent methods patients gallbladder cancer managed surgically 2000 2014 10 us academic institutions stratified based presence jaundice presentation defined bilirubin 4 mg ml requiring preoperative biliary drainage perioperative morbidity mortality overall survival compared jaundiced non jaundiced patients results 400 gallbladder cancer patients available preoperative data 108 27 presented jaundice 292 73 fraction patients eventually underwent curative intent resection much lower presence jaundice n 33 30 n 218 75 p 0 001 jaundiced patients experienced higher perioperative morbidity 69 vs 38 p 0 002 including much higher need reoperation 12 vs 1 p 0 003 however 90 day mortality 6 5 vs 3 6 p 0 35 significantly higher overall survival resection worse jaundiced patients median 14 vs 32 months p 0 001 subgroup analysis within jaundiced patients revealed favorable survival resection presence low ca19 9 50 median 40 vs 12 months p 0 003 absence lymphovascular invasion 40 vs 14 months p 0 014 conclusion jaundice powerful preoperative clinical sign inoperability poor outcome among gallbladder cancer patients however patients may still achieve long term survival resection especially preoperative ca19 9 levels low lymphovascular invasion noted pathologically stn","probabilities":0.9799733,"Title":"Gallbladder Cancer Presenting With Jaundice: Uniformly Fatal Or Still Potentially Curable?","Abstract":"Background: Jaundice as a presenting symptom of gallbladder cancer has traditionally been considered to be a sign of advanced disease, inoperability, and poor outcome. However, recent studies have demonstrated that a small subset of these patients can undergo resection with curative intent. \r\n\r\n Methods: Patients with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic institutions were stratified based on the presence of jaundice at presentation (defined as bilirubin ≥4 mg/ml or requiring preoperative biliary drainage). Perioperative morbidity, mortality, and overall survival were compared between jaundiced and non-jaundiced patients. \r\n\r\n Results: Of 400 gallbladder cancer patients with available preoperative data, 108 (27%) presented with jaundice while 292 (73%) did not. The fraction of patients who eventually underwent curative-intent resection was much lower in the presence of jaundice (n = 33, 30%) than not (n = 218, 75%; P < 0.001). Jaundiced patients experienced higher perioperative morbidity (69 vs. 38%; P = 0.002), including a much higher need for reoperation (12 vs. 1%; P = 0.003). However, 90-day mortality (6.5 vs. 3.6%; P = 0.35) was not significantly higher. Overall survival after resection was worse in jaundiced patients (median 14 vs. 32 months; P < 0.001). Further subgroup analysis within the jaundiced patients revealed a more favorable survival after resection in the presence of low CA19-9 < 50 (median 40 vs. 12 months; P = 0.003) and in the absence of lymphovascular invasion (40 vs. 14 months; P = 0.014). \r\n\r\n Conclusion: Jaundice is a powerful preoperative clinical sign of inoperability and poor outcome among gallbladder cancer patients. However, some of these patients may still achieve long-term survival after resection, especially when preoperative CA19-9 levels are low and no lymphovascular invasion is noted pathologically.","Source":"STN","category":"HUMAN","training_data":"Gallbladder Cancer Presenting With Jaundice: Uniformly Fatal Or Still Potentially Curable? Background: Jaundice as a presenting symptom of gallbladder cancer has traditionally been considered to be a sign of advanced disease, inoperability, and poor outcome. However, recent studies have demonstrated that a small subset of these patients can undergo resection with curative intent. \r\n\r\n Methods: Patients with gallbladder cancer managed surgically from 2000 to 2014 in 10 US academic institutions were stratified based on the presence of jaundice at presentation (defined as bilirubin ≥4 mg/ml or requiring preoperative biliary drainage). Perioperative morbidity, mortality, and overall survival were compared between jaundiced and non-jaundiced patients. \r\n\r\n Results: Of 400 gallbladder cancer patients with available preoperative data, 108 (27%) presented with jaundice while 292 (73%) did not. The fraction of patients who eventually underwent curative-intent resection was much lower in the presence of jaundice (n = 33, 30%) than not (n = 218, 75%; P < 0.001). Jaundiced patients experienced higher perioperative morbidity (69 vs. 38%; P = 0.002), including a much higher need for reoperation (12 vs. 1%; P = 0.003). However, 90-day mortality (6.5 vs. 3.6%; P = 0.35) was not significantly higher. Overall survival after resection was worse in jaundiced patients (median 14 vs. 32 months; P < 0.001). Further subgroup analysis within the jaundiced patients revealed a more favorable survival after resection in the presence of low CA19-9 < 50 (median 40 vs. 12 months; P = 0.003) and in the absence of lymphovascular invasion (40 vs. 14 months; P = 0.014). \r\n\r\n Conclusion: Jaundice is a powerful preoperative clinical sign of inoperability and poor outcome among gallbladder cancer patients. However, some of these patients may still achieve long-term survival after resection, especially when preoperative CA19-9 levels are low and no lymphovascular invasion is noted pathologically. STN","prediction_labels":"HUMAN"},{"cleaned":"sprr2a expression cholangiocarcinoma increases local tumor invasiveness prevents metastasis cholangiocarcinoma morbidity mortality attributable local invasiveness regional lymph node distant organ metastasis cholangiocarcinoma progression follows series sequential events resemble wound healing reactions local invasion resembles epithelial migration phase involving epithelial mesenchymal transition emt colonization distant sites resembles epithelial restitution seen reverse process mesenchymal epithelial transition met study compare vivo local metastatic growth potential cholangiocarcinoma cell lines respect expression novel pstat3 dependent biliary epithelial cell wound healing protein small proline rich protein 2a sprr2a sprr2a associated local aggressiveness decreased metastatic capabilities cancers stable sprr2a transfection two cholangiocarcinoma cell lines sg231 hucct 1 previously shown us induce permanent emt resulted local aggressiveness inability form metastases contrast sprr2a negative epithelial control cells showed relatively poor local aggressiveness readily formed metastatic tumors post intrasplenic injection cell tracking showed mesenchymal sprr2a cells trapped liver rapidly cleared mesenteric lymph nodes form metastases whereas b epithelial sprr2a controls primarily entrapped within muc 1 associated liver micro infarcts later evolved metastatic colonies sprr2a associated tumor behavior mimicked muc1 shrna induced emt like sprr2a cells showed reduced metastatic capabilities cholangiocarcinoma local invasion involves emt processes whereas met muc1 expression promote metastasis better understanding disease progression help target treatment deadly neoplasm stn","probabilities":0.9467213,"Title":"Sprr2A Expression In Cholangiocarcinoma Increases Local Tumor Invasiveness But Prevents Metastasis","Abstract":"Cholangiocarcinoma morbidity and mortality is attributable to local invasiveness and regional lymph node and distant organ metastasis. Cholangiocarcinoma progression follows a series of sequential events that resemble wound healing reactions: local invasion resembles the epithelial migration phase involving epithelial-mesenchymal transition (EMT); colonization at distant sites resembles epithelial restitution seen during the reverse process, mesenchymal-epithelial transition (MET). In this study we compare the in vivo local and metastatic growth potential of cholangiocarcinoma cell lines with respect to expression of a novel pSTAT3-dependent, biliary epithelial cell wound healing protein, small proline-rich protein 2A (SPRR2A). SPRR2A has been associated with local aggressiveness, but decreased metastatic capabilities in other cancers. Stable SPRR2A transfection into two cholangiocarcinoma cell lines (SG231 and HuCCT-1), previously shown by us to induce permanent EMT, resulted in local aggressiveness but an inability to form metastases. In contrast, SPRR2A-negative epithelial control cells showed relatively poor local aggressiveness, but readily formed metastatic tumors. Post-intrasplenic injection cell tracking showed that: (a) mesenchymal (SPRR2A+) cells were not trapped in the liver, but were rapidly cleared through mesenteric lymph nodes and did not form metastases; whereas (b) epithelial (SPRR2A-) controls were primarily entrapped within MUC-1-associated liver \"micro-infarcts\" that later evolved into metastatic colonies. SPRR2A-associated tumor behavior was mimicked by MUC1 shRNA, which induced EMT and, like SPRR2A+ cells, showed reduced metastatic capabilities. Cholangiocarcinoma local invasion involves EMT processes, whereas MET and MUC1 expression promote metastasis. A better understanding of disease progression should help target treatment for this deadly neoplasm.","Source":"STN","category":"ANIMAL","training_data":"Sprr2A Expression In Cholangiocarcinoma Increases Local Tumor Invasiveness But Prevents Metastasis Cholangiocarcinoma morbidity and mortality is attributable to local invasiveness and regional lymph node and distant organ metastasis. Cholangiocarcinoma progression follows a series of sequential events that resemble wound healing reactions: local invasion resembles the epithelial migration phase involving epithelial-mesenchymal transition (EMT); colonization at distant sites resembles epithelial restitution seen during the reverse process, mesenchymal-epithelial transition (MET). In this study we compare the in vivo local and metastatic growth potential of cholangiocarcinoma cell lines with respect to expression of a novel pSTAT3-dependent, biliary epithelial cell wound healing protein, small proline-rich protein 2A (SPRR2A). SPRR2A has been associated with local aggressiveness, but decreased metastatic capabilities in other cancers. Stable SPRR2A transfection into two cholangiocarcinoma cell lines (SG231 and HuCCT-1), previously shown by us to induce permanent EMT, resulted in local aggressiveness but an inability to form metastases. In contrast, SPRR2A-negative epithelial control cells showed relatively poor local aggressiveness, but readily formed metastatic tumors. Post-intrasplenic injection cell tracking showed that: (a) mesenchymal (SPRR2A+) cells were not trapped in the liver, but were rapidly cleared through mesenteric lymph nodes and did not form metastases; whereas (b) epithelial (SPRR2A-) controls were primarily entrapped within MUC-1-associated liver \"micro-infarcts\" that later evolved into metastatic colonies. SPRR2A-associated tumor behavior was mimicked by MUC1 shRNA, which induced EMT and, like SPRR2A+ cells, showed reduced metastatic capabilities. Cholangiocarcinoma local invasion involves EMT processes, whereas MET and MUC1 expression promote metastasis. A better understanding of disease progression should help target treatment for this deadly neoplasm. STN","prediction_labels":"ANIMAL"},{"cleaned":"cholelithiasis gallbladder cancer coincidence cofactor cause background gallstones associated cancers gallbladder actual nature relationship needs clarified aid recommendations need prophylactic cholecystectomy methods systematic search scientific literature carried using medline embase cochrane central register controlled trials years 1891 2009 obtain access publications involving gallstones gallbladder cancer results epidemiological evidence supports causal relationship gallstones gallbladder cancer studies demonstrated relatively low incidence gallbladder cancer countries reporting high incidence gallstones whole studies gallstones appear causative role cancer risk increases increasing size volume weight number stones impact duration stone composition clear experimental evidence studies examining impact artificially introducing gallstones gallbladder failed lead carcinogenesis conclusions evidence current time indicates gallstones cofactor causation gallbladder cancer absolute proof role cause gallbladder cancer lacking recommendation prophylactic cholecystectomy countries reporting high incidence gallbladder cancer associated gallstones needs tailored epidemiological profile place pubmed","probabilities":0.9799733,"Title":"Cholelithiasis in gallbladder cancer: coincidence, cofactor, or cause!","Abstract":"BACKGROUND: While gallstones are associated with cancers of the gallbladder, the actual nature of their relationship needs to be clarified. This would aid the recommendations on the need for prophylactic cholecystectomy. METHODS: A systematic search of the scientific literature was carried out using the Medline, the Embase, and the Cochrane Central Register of Controlled Trials for the years 1891-2009 to obtain access to all publications involving gallstones in gallbladder cancer. RESULTS: While some epidemiological evidence supports a causal relationship for gallstones in gallbladder cancer, other studies have demonstrated a relatively low incidence of gallbladder cancer in countries reporting a high incidence of gallstones as a whole. In those studies where gallstones appear to have a causative role for cancer, the risk increases with increasing size, volume and weight, and number of the stones. The impact of duration of the stone or its composition is not clear. Experimental evidence from studies examining the impact of artificially introducing gallstones in the gallbladder has failed to lead to carcinogenesis. CONCLUSIONS: The evidence at the current time indicates that gallstones are a cofactor in the causation of gallbladder cancer. Absolute proof of their role as a cause for gallbladder cancer is lacking. The recommendation for prophylactic cholecystectomy in countries reporting a high incidence of gallbladder cancer and associated gallstones needs to be tailored to the epidemiological profile of the place.","Source":"PubMed","category":"HUMAN","training_data":"Cholelithiasis in gallbladder cancer: coincidence, cofactor, or cause! BACKGROUND: While gallstones are associated with cancers of the gallbladder, the actual nature of their relationship needs to be clarified. This would aid the recommendations on the need for prophylactic cholecystectomy. METHODS: A systematic search of the scientific literature was carried out using the Medline, the Embase, and the Cochrane Central Register of Controlled Trials for the years 1891-2009 to obtain access to all publications involving gallstones in gallbladder cancer. RESULTS: While some epidemiological evidence supports a causal relationship for gallstones in gallbladder cancer, other studies have demonstrated a relatively low incidence of gallbladder cancer in countries reporting a high incidence of gallstones as a whole. In those studies where gallstones appear to have a causative role for cancer, the risk increases with increasing size, volume and weight, and number of the stones. The impact of duration of the stone or its composition is not clear. Experimental evidence from studies examining the impact of artificially introducing gallstones in the gallbladder has failed to lead to carcinogenesis. CONCLUSIONS: The evidence at the current time indicates that gallstones are a cofactor in the causation of gallbladder cancer. Absolute proof of their role as a cause for gallbladder cancer is lacking. The recommendation for prophylactic cholecystectomy in countries reporting a high incidence of gallbladder cancer and associated gallstones needs to be tailored to the epidemiological profile of the place. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect adjuvant chemotherapy patients intrahepatic cholangiocarcinoma matched pair analysis purpose purpose study identify prognostic factors patients intrahepatic cholangiocarcinoma icc treated resection investigate effect adjuvant chemotherapy ct methods patients icc diagnosed 2000 2015 treated hannover medical school included clinicopathologic characteristics analyzed univariate multivariate analysis matched pair survival analysis patients without adjuvant ct matched prognostic factors results two hundred ten patients included median survival 28 7 months 1 3 5 year survival rates 72 8 29 6 14 1 respectively multivariate analysis lymph node involvement p 0 006 hr 1 84 larger tumor size p 0 013 hr 1 79 vascular invasion p 0 038 hr 1 70 prolongation prothrombin time p 0 001 hr 4 20 significantly related poor survival thirty nine patients received adjuvant ct 60 lymph node involvement 25 patients without adjuvant ct matched identified prognostic factors median survival patients adjuvant ct 33 5 months compared 18 months control group p 0 002 1 3 5 year survival rates 96 36 12 compared 60 4 0 non treated patients conclusions identified several prognostic factors patients icc treated resection data support use adjuvant ct patients icc results prospective randomized controlled studies clarify role adjuvant ct future pubmed","probabilities":0.9799733,"Title":"The effect of adjuvant chemotherapy in patients with intrahepatic cholangiocarcinoma: a matched pair analysis","Abstract":"PURPOSE: The purpose of this study was to identify prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC) treated with resection and to investigate the effect of adjuvant chemotherapy (CT). METHODS: Patients with ICC diagnosed between 2000 and 2015 treated at Hannover Medical School were included. Clinicopathologic characteristics were analyzed in univariate and multivariate analysis. In a matched pair survival analysis, patients with or without adjuvant CT were matched by these prognostic factors. RESULTS: Two hundred and ten patients were included. Median survival was 28.7 months, 1-, 3-, and 5-year survival rates were 72.8%, 29.6%, and 14.1%, respectively. In multivariate analysis, lymph node involvement (p = 0.006, HR 1.84), larger tumor size (p = 0.013, HR 1.79), vascular invasion (p = 0.038, HR 1.70), and prolongation of prothrombin time (p < 0.001, HR 4.20) were significantly related to poor survival. Thirty-nine patients received adjuvant CT of which 60% had lymph node involvement. Each 25 patients with and without adjuvant CT were matched to the identified prognostic factors. The median survival of patients with adjuvant CT was 33.5 months, compared to 18 months in the control group (p = 0.002). The 1-, 3-, and 5-year survival rates were 96, 36, and 12%, compared to 60, 4, and 0% in non-treated patients. CONCLUSIONS: We identified several prognostic factors for patients with ICC treated with resection. Our data support the use of adjuvant CT in patients with ICC. The results of prospective randomized controlled studies will clarify the role of adjuvant CT in the future.","Source":"PubMed","category":"HUMAN","training_data":"The effect of adjuvant chemotherapy in patients with intrahepatic cholangiocarcinoma: a matched pair analysis PURPOSE: The purpose of this study was to identify prognostic factors of patients with intrahepatic cholangiocarcinoma (ICC) treated with resection and to investigate the effect of adjuvant chemotherapy (CT). METHODS: Patients with ICC diagnosed between 2000 and 2015 treated at Hannover Medical School were included. Clinicopathologic characteristics were analyzed in univariate and multivariate analysis. In a matched pair survival analysis, patients with or without adjuvant CT were matched by these prognostic factors. RESULTS: Two hundred and ten patients were included. Median survival was 28.7 months, 1-, 3-, and 5-year survival rates were 72.8%, 29.6%, and 14.1%, respectively. In multivariate analysis, lymph node involvement (p = 0.006, HR 1.84), larger tumor size (p = 0.013, HR 1.79), vascular invasion (p = 0.038, HR 1.70), and prolongation of prothrombin time (p < 0.001, HR 4.20) were significantly related to poor survival. Thirty-nine patients received adjuvant CT of which 60% had lymph node involvement. Each 25 patients with and without adjuvant CT were matched to the identified prognostic factors. The median survival of patients with adjuvant CT was 33.5 months, compared to 18 months in the control group (p = 0.002). The 1-, 3-, and 5-year survival rates were 96, 36, and 12%, compared to 60, 4, and 0% in non-treated patients. CONCLUSIONS: We identified several prognostic factors for patients with ICC treated with resection. Our data support the use of adjuvant CT in patients with ICC. The results of prospective randomized controlled studies will clarify the role of adjuvant CT in the future. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical significance cbs ccl21 gallbladder adenocarcinomas squamous cell adenosquamous carcinomas gallbladder cancer gbc rare disease high mortality however biomarkers carcinogenesis progression prognosis early diagnosis clinically available study investigated expressions cystathionine synthase cbs c c chemokine receptor 7 ccr7 protein clinical pathologic significances gallbladder squamous cell adenosquamous carcinomas sc asc adenocarcinomas ac cbs chemokine ligand 21 ccl21 expression measured using immunohistochemistry 69 sc ascs 146 acs significantly high percentage patients age 45 years lymph node metastasis invasion observed scs ascs compared acs p 0 05 ac sc asc patients positive cbs ccl21 expression exhibited high tumor lymph node metastasis stage lymph node metastasis invasion compared patients negative cbs ccl21 expression p 0 05 p 0 01 sc asc patients positive cbs expression prone larger tumor size negative expression p 0 05 positive cbs ccl21 expression correlated poor differentiation larger tumor size ac patients positive cbs ccl21 closely associated decreased overall survival sc asc ac patients p 0 05 p 0 01 independent factors poor prognosis cbs ccl21 showed good overall diagnostic performance sc asc auc 0 742 auc 0 764 respectively ac auc 0 734 auc 0 718 respectively conclusion positive cbs ccl21 expression closely associated clinical severity poor prognosis gbc marker diagnosis ac sc asc type gbc stn","probabilities":1.0,"Title":"Clinical Significance Of Cbs And Ccl21 In Gallbladder Adenocarcinomas And Squamous Cell/Adenosquamous Carcinomas","Abstract":"Gallbladder cancer (GBC) is a rare disease with high mortality. However, no biomarkers for the carcinogenesis, progression, prognosis, and early diagnosis are clinically available. This study investigated the expressions of cystathionine-β-synthase (CBS) and C-C chemokine receptor 7 (CCR7) protein and their clinical and pathologic significances in gallbladder squamous cell/adenosquamous carcinomas (SC/ASC) and adenocarcinomas (AC). CBS and chemokine ligand 21 (CCL21) expression was measured using immunohistochemistry in 69 SC/ASCs and 146 ACs. A significantly high percentage of patients with an age above 45 years, lymph node metastasis, and invasion was observed in the SCs/ASCs compared with ACs (P<0.05). Both AC and SC/ASC patients with positive CBS and CCL21 expression exhibited a high tumor-lymph node-metastasis stage, lymph node metastasis, and invasion compared with patients with negative CBS and CCL21 expression (P<0.05 or P<0.01). SC/ASC patients with positive CBS expression was prone to have a larger tumor size than those with negative expression (P<0.05). Positive CBS and CCL21 expression correlated with poor differentiation and larger tumor size in AC patients. Positive CBS and CCL21 are closely associated with a decreased overall survival in SC/ASC and AC patients (P<0.05 or P<0.01) and were independent factors for a poor-prognosis. Both CBS and CCL21 showed a good overall diagnostic performance for SC/ASC (AUC=0.742 and AUC=0.764, respectively) and AC (AUC=0.734 and AUC=0.718, respectively). In conclusion, positive CBS and CCL21 expression are closely associated with the clinical severity and poor prognosis in GBC, and can be a marker for the diagnosis of AC and SC/ASC type of GBC.","Source":"STN","category":"HUMAN","training_data":"Clinical Significance Of Cbs And Ccl21 In Gallbladder Adenocarcinomas And Squamous Cell/Adenosquamous Carcinomas Gallbladder cancer (GBC) is a rare disease with high mortality. However, no biomarkers for the carcinogenesis, progression, prognosis, and early diagnosis are clinically available. This study investigated the expressions of cystathionine-β-synthase (CBS) and C-C chemokine receptor 7 (CCR7) protein and their clinical and pathologic significances in gallbladder squamous cell/adenosquamous carcinomas (SC/ASC) and adenocarcinomas (AC). CBS and chemokine ligand 21 (CCL21) expression was measured using immunohistochemistry in 69 SC/ASCs and 146 ACs. A significantly high percentage of patients with an age above 45 years, lymph node metastasis, and invasion was observed in the SCs/ASCs compared with ACs (P<0.05). Both AC and SC/ASC patients with positive CBS and CCL21 expression exhibited a high tumor-lymph node-metastasis stage, lymph node metastasis, and invasion compared with patients with negative CBS and CCL21 expression (P<0.05 or P<0.01). SC/ASC patients with positive CBS expression was prone to have a larger tumor size than those with negative expression (P<0.05). Positive CBS and CCL21 expression correlated with poor differentiation and larger tumor size in AC patients. Positive CBS and CCL21 are closely associated with a decreased overall survival in SC/ASC and AC patients (P<0.05 or P<0.01) and were independent factors for a poor-prognosis. Both CBS and CCL21 showed a good overall diagnostic performance for SC/ASC (AUC=0.742 and AUC=0.764, respectively) and AC (AUC=0.734 and AUC=0.718, respectively). In conclusion, positive CBS and CCL21 expression are closely associated with the clinical severity and poor prognosis in GBC, and can be a marker for the diagnosis of AC and SC/ASC type of GBC. STN","prediction_labels":"HUMAN"},{"cleaned":"prosurvival role heat shock factor 1 pathogenesis pancreatobiliary tumors several mechanisms evolved ensure survival cells adverse conditions heat shock response one evolutionarily conserved survival mechanism heat shock factor 1 hsf1 transcriptional regulator heat shock response nature prosurvival function hsf1 may contribute pathogenesis cancer current study investigates role hsf1 pathogenesis pancreatobiliary tumors hsf1 downregulated pancreatic cancer mia paca 2 s2 013 cholangiocarcinoma kmbc kmch cell lines hsf1 specific small interfering rna sirna nonsilencing sirna used control effect hsf1 downregulation viability apoptosis parameters e annexin v terminal deoxynucleotidyl transferase dutp mediated nick end labeling tunel caspase 3 measured evaluate cancer specific effects hsf1 effect hsf1 downregulation normal human pancreatic ductal cells also evaluated hsf1 abundantly expressed human pancreatobiliary cancer cell lines well pancreatic cancer tissue demonstrated western blot immunohistochemistry respectively inhibition hsf1 expression hsf1 sirna sequences leads time dependent death pancreatic cholangiocarcinoma cell lines downregulation hsf1 expression induces annexin v tunel positivity caspase 3 activation suggesting activation caspase dependent apoptotic pathway although caspase 3 inhibition protects cell death induced hsf1 expression completely prevent suggesting role caspase independent cell death hsf1 plays prosurvival role pathogenesis pancreatobiliary tumors modulation hsf1 activity therefore emerge novel therapeutic strategy cancer treatment stn","probabilities":0.9467213,"Title":"Prosurvival Role Of Heat Shock Factor 1 In The Pathogenesis Of Pancreatobiliary Tumors","Abstract":"Several mechanisms have evolved to ensure the survival of cells under adverse conditions. The heat shock response is one such evolutionarily conserved survival mechanism. Heat shock factor-1 (HSF1) is a transcriptional regulator of the heat shock response. By the very nature of its prosurvival function, HSF1 may contribute to the pathogenesis of cancer. The current study investigates the role of HSF1 in the pathogenesis of pancreatobiliary tumors. HSF1 was downregulated in pancreatic cancer (MIA PaCa-2 and S2-013) and cholangiocarcinoma (KMBC and KMCH) cell lines by HSF1-specific small interfering RNA (siRNA). Nonsilencing siRNA was used as control. The effect of HSF1 downregulation on viability and apoptosis parameters, i.e., annexin V, terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling (TUNEL), and caspase-3, was measured. To evaluate the cancer-specific effects of HSF1, the effect of HSF1 downregulation on normal human pancreatic ductal cells was also evaluated. HSF1 is abundantly expressed in human pancreatobiliary cancer cell lines, as well as in pancreatic cancer tissue, as demonstrated by Western blot and immunohistochemistry, respectively. Inhibition of HSF1 expression by the HSF1 siRNA sequences leads to time-dependent death in pancreatic and cholangiocarcinoma cell lines. Downregulation of HSF1 expression induces annexin V and TUNEL positivity and caspase-3 activation, suggesting activation of a caspase-dependent apoptotic pathway. Although caspase-3 inhibition protects against cell death induced by HSF1 expression, it does not completely prevent it, suggesting a role for caspase-independent cell death. HSF1 plays a prosurvival role in the pathogenesis of pancreatobiliary tumors. Modulation of HSF1 activity could therefore emerge as a novel therapeutic strategy for cancer treatment.","Source":"STN","category":"ANIMAL","training_data":"Prosurvival Role Of Heat Shock Factor 1 In The Pathogenesis Of Pancreatobiliary Tumors Several mechanisms have evolved to ensure the survival of cells under adverse conditions. The heat shock response is one such evolutionarily conserved survival mechanism. Heat shock factor-1 (HSF1) is a transcriptional regulator of the heat shock response. By the very nature of its prosurvival function, HSF1 may contribute to the pathogenesis of cancer. The current study investigates the role of HSF1 in the pathogenesis of pancreatobiliary tumors. HSF1 was downregulated in pancreatic cancer (MIA PaCa-2 and S2-013) and cholangiocarcinoma (KMBC and KMCH) cell lines by HSF1-specific small interfering RNA (siRNA). Nonsilencing siRNA was used as control. The effect of HSF1 downregulation on viability and apoptosis parameters, i.e., annexin V, terminal deoxynucleotidyl transferase dUTP-mediated nick end labeling (TUNEL), and caspase-3, was measured. To evaluate the cancer-specific effects of HSF1, the effect of HSF1 downregulation on normal human pancreatic ductal cells was also evaluated. HSF1 is abundantly expressed in human pancreatobiliary cancer cell lines, as well as in pancreatic cancer tissue, as demonstrated by Western blot and immunohistochemistry, respectively. Inhibition of HSF1 expression by the HSF1 siRNA sequences leads to time-dependent death in pancreatic and cholangiocarcinoma cell lines. Downregulation of HSF1 expression induces annexin V and TUNEL positivity and caspase-3 activation, suggesting activation of a caspase-dependent apoptotic pathway. Although caspase-3 inhibition protects against cell death induced by HSF1 expression, it does not completely prevent it, suggesting a role for caspase-independent cell death. HSF1 plays a prosurvival role in the pathogenesis of pancreatobiliary tumors. Modulation of HSF1 activity could therefore emerge as a novel therapeutic strategy for cancer treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"association estrogen receptor 1 esr1 genetic variations cancer risk meta analysis purpose emerging published reports association estrogen receptor 1 esr1 genetic variation cancer susceptibility inconsistent review meta analysis performed achieve precise evaluation relationship methods literature search pubmed database conducted inception study april 1st 2014 crude odds ratios ors 95 confidence intervals 95 cis calculated assess association results 87 studies enrolled meta analysis results indicated pvuii c polymorphism associated increased risk hepatocellular carcinoma hcc prostate cancer contrast decreased risk gallbladder cancer significant association found asian caucasian populations furthermore xbai g genetic variation associated increased risk prostate cancer related race addition t594t g polymorphisms significantly associated increased risk cancer especially asian populations conclusions meta analysis indicated pvuii c genetic variation may risk factor hcc prostate cancer gallbladder cancer meanwhile xbai g polymorphism may potential prognostic factor prostate cancer furthermore t594t g closely related cancer susceptibility especially asian populations pubmed","probabilities":0.9799733,"Title":"Association between estrogen receptor 1 (ESR1) genetic variations and cancer risk: a meta-analysis","Abstract":"PURPOSE: Emerging published reports on the association between estrogen receptor 1 (ESR1) genetic variation and cancer susceptibility are inconsistent. This review and meta- analysis was performed to achieve a more precise evaluation of this relationship. METHODS: A literature search of PubMed database was conducted from the inception of this study through April 1st 2014. Crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the association. RESULTS: 87 studies were enrolled in this meta-analysis. The results indicated that PvuII (T>C) polymorphism was associated with an increased risk of hepatocellular carcinoma (HCC) and prostate cancer, in contrast with the decreased risk of gallbladder cancer. No significant association was found in Asian and Caucasian populations. Furthermore, XbaI (A>G) genetic variation was only associated with an increased risk of prostate cancer, but was not related with race. In addition, T594T (G>A) polymorphisms were significantly associated with an increased risk of cancer, especially in Asian populations. CONCLUSIONS: This meta-analysis indicated that PvuII (T>C) genetic variation may be risk factor for HCC, prostate cancer and gallbladder cancer. Meanwhile, XbaI (A>G) polymorphism may be potential prognostic factor for prostate cancer. Furthermore, T594T (G>A) was closely related with cancer susceptibility, especially in Asian populations.","Source":"PubMed","category":"HUMAN","training_data":"Association between estrogen receptor 1 (ESR1) genetic variations and cancer risk: a meta-analysis PURPOSE: Emerging published reports on the association between estrogen receptor 1 (ESR1) genetic variation and cancer susceptibility are inconsistent. This review and meta- analysis was performed to achieve a more precise evaluation of this relationship. METHODS: A literature search of PubMed database was conducted from the inception of this study through April 1st 2014. Crude odds ratios (ORs) with 95% confidence intervals (95% CIs) were calculated to assess the association. RESULTS: 87 studies were enrolled in this meta-analysis. The results indicated that PvuII (T>C) polymorphism was associated with an increased risk of hepatocellular carcinoma (HCC) and prostate cancer, in contrast with the decreased risk of gallbladder cancer. No significant association was found in Asian and Caucasian populations. Furthermore, XbaI (A>G) genetic variation was only associated with an increased risk of prostate cancer, but was not related with race. In addition, T594T (G>A) polymorphisms were significantly associated with an increased risk of cancer, especially in Asian populations. CONCLUSIONS: This meta-analysis indicated that PvuII (T>C) genetic variation may be risk factor for HCC, prostate cancer and gallbladder cancer. Meanwhile, XbaI (A>G) polymorphism may be potential prognostic factor for prostate cancer. Furthermore, T594T (G>A) was closely related with cancer susceptibility, especially in Asian populations. PubMed","prediction_labels":"HUMAN"},{"cleaned":"liver fluke associated biliary tract cancer cholangiocarcinoma cca aggressive cancer arising epithelial cells bile duct patients cca unresectable tumor time diagnosis western countries risk cca increases patients primary sclerosing cholangitis whereas liver fluke infection appears major risk factor cca asian countries diagnosis liver fluke infection often relies stool samples including microscopic examination polymerase chain reaction based assays fluke antigen detection tests serum saliva urine samples also potentially diagnostic presence liver fluke along exogenous carcinogens magnifies risk cca people living endemic areas liver fluke cholangiocarcinoma carcinogenesis pathways consist mechanical damage bile duct epithelium immunopathologic cellular reactions liver fluke antigens excretory secretory products liver fluke induced changes biliary tract microbiome effects repeated treatment liver fluke vaccine novel biomarkers needed primary secondary prevention cca endemic areas importantly climate change exerts effect vector borne parasitic diseases awareness liver fluke enhanced potentially migrated habitat areas pubmed","probabilities":0.5555556,"Title":"Liver Fluke-Associated Biliary Tract Cancer","Abstract":"Cholangiocarcinoma (CCA) is an aggressive cancer arising from epithelial cells of the bile duct. Most patients with CCA have an unresectable tumor at the time of diagnosis. In Western countries, the risk of CCA increases in patients with primary sclerosing cholangitis, whereas liver fluke infection appears to be the major risk factor for CCA in Asian countries. A diagnosis of liver fluke infection often relies on stool samples, including microscopic examination, polymerase chain reaction-based assays, and fluke antigen detection. Tests of serum, saliva and urine samples are also potentially diagnostic. The presence of liver fluke along with exogenous carcinogens magnifies the risk of CCA in people living in endemic areas. The \"liver fluke-cholangiocarcinoma\" carcinogenesis pathways consist of mechanical damage to the bile duct epithelium, immunopathologic and cellular reactions to the liver fluke's antigens and excretory/secretory products, liver fluke-induced changes in the biliary tract microbiome and the effects of repeated treatment for liver fluke. A vaccine and novel biomarkers are needed for the primary and secondary prevention of CCA in endemic areas. Importantly, climate change exerts an effect on vector-borne parasitic diseases, and awareness of liver fluke should be enhanced in potentially migrated habitat areas.","Source":"PubMed","category":"HUMAN","training_data":"Liver Fluke-Associated Biliary Tract Cancer Cholangiocarcinoma (CCA) is an aggressive cancer arising from epithelial cells of the bile duct. Most patients with CCA have an unresectable tumor at the time of diagnosis. In Western countries, the risk of CCA increases in patients with primary sclerosing cholangitis, whereas liver fluke infection appears to be the major risk factor for CCA in Asian countries. A diagnosis of liver fluke infection often relies on stool samples, including microscopic examination, polymerase chain reaction-based assays, and fluke antigen detection. Tests of serum, saliva and urine samples are also potentially diagnostic. The presence of liver fluke along with exogenous carcinogens magnifies the risk of CCA in people living in endemic areas. The \"liver fluke-cholangiocarcinoma\" carcinogenesis pathways consist of mechanical damage to the bile duct epithelium, immunopathologic and cellular reactions to the liver fluke's antigens and excretory/secretory products, liver fluke-induced changes in the biliary tract microbiome and the effects of repeated treatment for liver fluke. A vaccine and novel biomarkers are needed for the primary and secondary prevention of CCA in endemic areas. Importantly, climate change exerts an effect on vector-borne parasitic diseases, and awareness of liver fluke should be enhanced in potentially migrated habitat areas. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"correlation metastatic lymph node ratio prognosis patients extrahepatic cholangiocarcinoma aim investigate prognostic value metastatic lymph node ratio mlnr extrahepatic cholangiocarcinoma ecc patients undergoing radical resection methods seventy eight patients ecc enrolled associations various clinicopathologic factors prognosis investigated kaplan meier analyses cox proportional hazards model used multivariate survival analysis results overall three five year survival rates 47 26 23 99 respectively mlnr 0 0 0 2 0 2 0 5 0 5 corresponded five year survival rates 28 59 21 60 18 84 10 03 respectively univariate analysis showed degree tumor differentiation lymph node metastasis mlnr tumor node metastasis tnm stage margin status closely associated postoperative survival ecc patients p 0 05 multivariate analysis showed mlnr tnm stage independent prognostic factors pancreaticoduodenectomy hr 2 13 95 ci 1 45 3 11 p 0 01 hr 1 97 95 ci 1 17 3 31 p 0 01 respectively median survival time mlnr 0 5 0 2 0 5 0 0 2 0 15 mo 24 mo 23 mo 35 5 mo respectively statistical differences survival time patients different mlnr 2 15 38 p 0 01 conclusion mlnr independent prognostic factor ecc patients radical resection useful predicting postoperative survival pubmed","probabilities":0.9799733,"Title":"Correlation between metastatic lymph node ratio and prognosis in patients with extrahepatic cholangiocarcinoma","Abstract":"AIM: To investigate the prognostic value of metastatic lymph node ratio (MLNR) in extrahepatic cholangiocarcinoma (ECC) patients undergoing radical resection. METHODS: Seventy-eight patients with ECC were enrolled. Associations between various clinicopathologic factors and prognosis were investigated by Kaplan-Meier analyses. The Cox proportional-hazards model was used for multivariate survival analysis. RESULTS: The overall three- and five-year survival rates were 47.26% and 23.99%, respectively. MLNR of 0, 0-0.2, 0.2-0.5, and > 0.5 corresponded to five-year survival rates of 28.59%, 21.60%, 18.84%, and 10.03%, respectively. Univariate analysis showed that degree of tumor differentiation, lymph node metastasis, MLNR, tumor-node-metastasis (TNM) stage, and margin status were closely associated with postoperative survival in ECC patients (P < 0.05). Multivariate analysis showed that MLNR and TNM stage were independent prognostic factors after pancreaticoduodenectomy (HR = 2.13, 95%CI: 1.45-3.11; P < 0.01; and HR = 1.97, 95%CI: 1.17-3.31; P = 0.01, respectively). The median survival time for MLNR > 0.5, 0.2-0.5, 0-0.2, and 0 was 15 mo, 24 mo, 23 mo, and 35.5 mo, respectively. There were statistical differences in survival time between patients with different MLNR (χ(2) = 15.38; P < 0.01). CONCLUSION: MLNR is an independent prognostic factor for ECC patients after radical resection and is useful for predicting postoperative survival.","Source":"PubMed","category":"HUMAN","training_data":"Correlation between metastatic lymph node ratio and prognosis in patients with extrahepatic cholangiocarcinoma AIM: To investigate the prognostic value of metastatic lymph node ratio (MLNR) in extrahepatic cholangiocarcinoma (ECC) patients undergoing radical resection. METHODS: Seventy-eight patients with ECC were enrolled. Associations between various clinicopathologic factors and prognosis were investigated by Kaplan-Meier analyses. The Cox proportional-hazards model was used for multivariate survival analysis. RESULTS: The overall three- and five-year survival rates were 47.26% and 23.99%, respectively. MLNR of 0, 0-0.2, 0.2-0.5, and > 0.5 corresponded to five-year survival rates of 28.59%, 21.60%, 18.84%, and 10.03%, respectively. Univariate analysis showed that degree of tumor differentiation, lymph node metastasis, MLNR, tumor-node-metastasis (TNM) stage, and margin status were closely associated with postoperative survival in ECC patients (P < 0.05). Multivariate analysis showed that MLNR and TNM stage were independent prognostic factors after pancreaticoduodenectomy (HR = 2.13, 95%CI: 1.45-3.11; P < 0.01; and HR = 1.97, 95%CI: 1.17-3.31; P = 0.01, respectively). The median survival time for MLNR > 0.5, 0.2-0.5, 0-0.2, and 0 was 15 mo, 24 mo, 23 mo, and 35.5 mo, respectively. There were statistical differences in survival time between patients with different MLNR (χ(2) = 15.38; P < 0.01). CONCLUSION: MLNR is an independent prognostic factor for ECC patients after radical resection and is useful for predicting postoperative survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison inflammation based prognostic scores patients extrahepatic bile duct cancer pancreaticoduodenectomy background inflammation based prognostic scores associated tumor recurrence survival various cancers aim study identify significance inflammation based prognostic scores detect useful score patients distal extrahepatic bile duct cancer pancreaticoduodenectomy methods 2000 2015 121 patients enrolled retrospective study relationship clinicopathological variables including various prognostic scores disease free dfs well overall os survival investigated univariate analysis area receiver operating characteristics curve calculated compare predictive ability scoring system multivariate analysis performed identify clinicopathological variables associated results univariate analysis glasgow prognostic score gps mgps c reactive protein alb ratio score prognostic index preoperative monocyte count significant risk factors dfs os area receiver operating characteristics curve gps consistently larger comparison four scores dfs well os multivariate analysis gps independent risk factor tumor recurrence poor prognosis conclusions gps score independent tumor recurrence prognostic factor patients distal extrahepatic bile duct cancer superior prognostic scores pubmed","probabilities":0.9799733,"Title":"The Comparison of Inflammation-Based Prognostic Scores in Patients With Extrahepatic Bile Duct Cancer After Pancreaticoduodenectomy","Abstract":"BACKGROUND: Inflammation-based prognostic scores are associated with tumor recurrence and survival in various cancers. The aim of this study was to identify the significance of inflammation-based prognostic scores and to detect the most useful score in patients with distal extrahepatic bile duct cancer after pancreaticoduodenectomy. METHODS: Between 2000 and 2015, 121 patients were enrolled in this retrospective study. The relationship between clinicopathological variables including various prognostic scores and disease-free (DFS) as well as overall (OS) survival was investigated by univariate analysis. The area under the receiver operating characteristics curve was calculated to compare the predictive ability of each scoring system. Multivariate analysis was performed to identify the clinicopathological variables associated. RESULTS: In univariate analysis, Glasgow prognostic score (GPS), mGPS, C-reactive protein/Alb ratio score, prognostic index, and preoperative monocyte count were significant risk factors for both DFS and OS. The area under the receiver operating characteristics curve of GPS is consistently larger in comparison with other four scores in both DFS as well as OS. In multivariate analysis, GPS was an independent risk factor of both tumor recurrence and poor prognosis. CONCLUSIONS: GPS score is an independent tumor recurrence and prognostic factor in patients with distal extrahepatic bile duct cancer and is superior to the other prognostic scores.","Source":"PubMed","category":"HUMAN","training_data":"The Comparison of Inflammation-Based Prognostic Scores in Patients With Extrahepatic Bile Duct Cancer After Pancreaticoduodenectomy BACKGROUND: Inflammation-based prognostic scores are associated with tumor recurrence and survival in various cancers. The aim of this study was to identify the significance of inflammation-based prognostic scores and to detect the most useful score in patients with distal extrahepatic bile duct cancer after pancreaticoduodenectomy. METHODS: Between 2000 and 2015, 121 patients were enrolled in this retrospective study. The relationship between clinicopathological variables including various prognostic scores and disease-free (DFS) as well as overall (OS) survival was investigated by univariate analysis. The area under the receiver operating characteristics curve was calculated to compare the predictive ability of each scoring system. Multivariate analysis was performed to identify the clinicopathological variables associated. RESULTS: In univariate analysis, Glasgow prognostic score (GPS), mGPS, C-reactive protein/Alb ratio score, prognostic index, and preoperative monocyte count were significant risk factors for both DFS and OS. The area under the receiver operating characteristics curve of GPS is consistently larger in comparison with other four scores in both DFS as well as OS. In multivariate analysis, GPS was an independent risk factor of both tumor recurrence and poor prognosis. CONCLUSIONS: GPS score is an independent tumor recurrence and prognostic factor in patients with distal extrahepatic bile duct cancer and is superior to the other prognostic scores. PubMed","prediction_labels":"HUMAN"},{"cleaned":"safe curative approach incidental gallbladder cancer abstract available google scholar","probabilities":0.9799733,"Title":"A Safe And Curative Approach For Incidental Gallbladder Cancer","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"A Safe And Curative Approach For Incidental Gallbladder Cancer Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinical implications cytotoxic lymphocyte antigen 4 expression tumor cells tumor infiltrating lymphocytes extrahepatic bile duct cancer patients undergoing surgery plus adjuvant chemoradiotherapy background currently limited knowledge role tumor specific immunity cholangiocarcinoma objective study evaluated clinical implications cytotoxic lymphocyte antigen 4 ctla 4 expression levels cd4 cd8 tumor infiltrating lymphocytes tils extrahepatic bile duct ehbd cancer patients methods immunohistochemistry ctla 4 cd4 cd8 performed 77 ehbd cancer patients undergoing surgery plus adjuvant chemoradiotherapy ctla 4 expression tumor cells tils assessed using h scores proportion ctla 4 lymphocytes respectively results optimal cutoff values determined maximal chi square method overall survival os data patients ctla 4 h score 70 proportion ctla 4 tils 0 15 showed higher mean density cd8 cd4 tils respectively p 0 025 cd8 p 0 055 cd4 tils high ctla 4 h score level associated prolonged os disease free interval dfi p 0 025 0 004 respectively differential levels ctla 4 h score according hilar non hilar locations high rate 32 vs 68 respectively p 0 013 exploratory subgroup analysis demonstrated associations ctla 4 expression os dfi confined hilar tumors p 0 003 0 001 respectively non hilar ones p 0 613 0 888 respectively conclusions study demonstrates potential prognostic relevance ctla 4 expression ehbd cancer suggest differential survival impact ctla 4 expression level according different tumor locations pubmed","probabilities":0.9799733,"Title":"Clinical Implications of Cytotoxic T Lymphocyte Antigen-4 Expression on Tumor Cells and Tumor-Infiltrating Lymphocytes in Extrahepatic Bile Duct Cancer Patients Undergoing Surgery Plus Adjuvant Chemoradiotherapy","Abstract":"BACKGROUND: There currently is only limited knowledge on the role of tumor-specific immunity in cholangiocarcinoma. OBJECTIVE: This study evaluated the clinical implications of cytotoxic T lymphocyte antigen-4 (CTLA-4) expression levels and CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TILs) in extrahepatic bile duct (EHBD) cancer. PATIENTS AND METHODS: Immunohistochemistry of CTLA-4, CD4, and CD8 was performed for 77 EHBD cancer patients undergoing surgery plus adjuvant chemoradiotherapy. CTLA-4 expression on tumor cells and TILs were assessed by using H-scores and the proportion of CTLA-4(+) lymphocytes, respectively. RESULTS: With optimal cutoff values determined by a maximal chi-square method with overall survival (OS) data, patients with CTLA-4 H-score >70 and a proportion of CTLA-4(+) TILs >0.15 showed higher mean density of CD8(+) and CD4(+) TILs, respectively (P = 0.025 for CD8(+) and P = 0.055 for CD4(+) TILs). The high CTLA-4 H-score level was associated with prolonged OS and disease-free interval (DFI) (P = 0.025 and 0.004, respectively). With differential levels of CTLA-4 H-score according to hilar and non-hilar locations (high rate 32 vs. 68%, respectively; P = 0.013), an exploratory subgroup analysis demonstrated that the associations between the CTLA-4 expression and OS and DFI were confined to hilar tumors (P = 0.003 and <0.001, respectively), but not to non-hilar ones (P = 0.613 and 0.888, respectively). CONCLUSIONS: This study demonstrates a potential prognostic relevance of CTLA-4 expression in EHBD cancer. We suggest a differential survival impact of the CTLA-4 expression level according to different tumor locations.","Source":"PubMed","category":"HUMAN","training_data":"Clinical Implications of Cytotoxic T Lymphocyte Antigen-4 Expression on Tumor Cells and Tumor-Infiltrating Lymphocytes in Extrahepatic Bile Duct Cancer Patients Undergoing Surgery Plus Adjuvant Chemoradiotherapy BACKGROUND: There currently is only limited knowledge on the role of tumor-specific immunity in cholangiocarcinoma. OBJECTIVE: This study evaluated the clinical implications of cytotoxic T lymphocyte antigen-4 (CTLA-4) expression levels and CD4(+) and CD8(+) tumor-infiltrating lymphocytes (TILs) in extrahepatic bile duct (EHBD) cancer. PATIENTS AND METHODS: Immunohistochemistry of CTLA-4, CD4, and CD8 was performed for 77 EHBD cancer patients undergoing surgery plus adjuvant chemoradiotherapy. CTLA-4 expression on tumor cells and TILs were assessed by using H-scores and the proportion of CTLA-4(+) lymphocytes, respectively. RESULTS: With optimal cutoff values determined by a maximal chi-square method with overall survival (OS) data, patients with CTLA-4 H-score >70 and a proportion of CTLA-4(+) TILs >0.15 showed higher mean density of CD8(+) and CD4(+) TILs, respectively (P = 0.025 for CD8(+) and P = 0.055 for CD4(+) TILs). The high CTLA-4 H-score level was associated with prolonged OS and disease-free interval (DFI) (P = 0.025 and 0.004, respectively). With differential levels of CTLA-4 H-score according to hilar and non-hilar locations (high rate 32 vs. 68%, respectively; P = 0.013), an exploratory subgroup analysis demonstrated that the associations between the CTLA-4 expression and OS and DFI were confined to hilar tumors (P = 0.003 and <0.001, respectively), but not to non-hilar ones (P = 0.613 and 0.888, respectively). CONCLUSIONS: This study demonstrates a potential prognostic relevance of CTLA-4 expression in EHBD cancer. We suggest a differential survival impact of the CTLA-4 expression level according to different tumor locations. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact site portal vein invasion patients surgically resected perihilar cholangiocarcinoma background aim study determine impact site portal vein invasion survival hepatectomy perihilar cholangiocarcinoma methods study classified 168 patients undergoing resection perihilar cholangiocarcinoma histologically without portal vein resection tumor invasion portal vein pv0 tumor invasion unilateral branches portal vein pvt3 tumor invasion main portal vein bilateral branches unilateral second order biliary radicals contralateral portal vein involvement pvt4 patients pvt4 subclassified m group cancer invasion limited tunica adventitia media group cancer invasion reaching tunica intima results patients 121 pv0 21 pvt3 26 pvt4 difference survival pv0 pvt3 groups p 267 pvt4 group worse prognosis pvt3 group p 046 addition m n 19 subgroups n 7 pvt4 worse prognoses pv0 pvt3 groups p 005 001 respectively patients subgroup pvt4 died within 9 months resection multivariate analysis pvt4 p 029 identified independent prognostic factor conclusions perihilar cholangiocarcinoma postoperative survival different patients without ipsilateral portal vein invasion although patients tumor invasion main contralateral branches portal vein especially tunica intima invasion extremely poor prognoses pubmed","probabilities":0.9799733,"Title":"Prognostic impact of the site of portal vein invasion in patients with surgically resected perihilar cholangiocarcinoma","Abstract":"BACKGROUND: The aim of this study was to determine the impact of the site of portal vein invasion on survival after hepatectomy for perihilar cholangiocarcinoma. METHODS: This study classified 168 patients undergoing resection for perihilar cholangiocarcinoma histologically as without portal vein resection or tumor invasion to the portal vein (PV0), with tumor invasion to unilateral branches of the portal vein (PVt3), or with tumor invasion to the main portal vein or its bilateral branches, or to unilateral second-order biliary radicals with contralateral portal vein involvement (PVt4). Patients in PVt4 were subclassified into the A-M group (cancer invasion limited to the tunica adventitia or media) or the I group (cancer invasion reaching the tunica intima). RESULTS: Of the patients, 121 were in PV0, 21 were in PVt3, and 26 were in PVt4. There was no difference in survival between the PV0 and PVt3 groups (P = .267). The PVt4 group had a worse prognosis than the PVt3 group (P = .046). In addition, the A-M (n = 19) and I subgroups (n = 7) of PVt4 had worse prognoses than the PV0 or PVt3 groups (P = .005 and < .001, respectively). All patients in the I subgroup of PVt4 died within 9 months after resection. On multivariate analysis, PVt4 (P = .029) was identified as an independent prognostic factor. CONCLUSIONS: In perihilar cholangiocarcinoma, postoperative survival was no different between patients with and without ipsilateral portal vein invasion, although patients with tumor invasion to the main or contralateral branches of the portal vein, especially with tunica intima invasion, had extremely poor prognoses.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic impact of the site of portal vein invasion in patients with surgically resected perihilar cholangiocarcinoma BACKGROUND: The aim of this study was to determine the impact of the site of portal vein invasion on survival after hepatectomy for perihilar cholangiocarcinoma. METHODS: This study classified 168 patients undergoing resection for perihilar cholangiocarcinoma histologically as without portal vein resection or tumor invasion to the portal vein (PV0), with tumor invasion to unilateral branches of the portal vein (PVt3), or with tumor invasion to the main portal vein or its bilateral branches, or to unilateral second-order biliary radicals with contralateral portal vein involvement (PVt4). Patients in PVt4 were subclassified into the A-M group (cancer invasion limited to the tunica adventitia or media) or the I group (cancer invasion reaching the tunica intima). RESULTS: Of the patients, 121 were in PV0, 21 were in PVt3, and 26 were in PVt4. There was no difference in survival between the PV0 and PVt3 groups (P = .267). The PVt4 group had a worse prognosis than the PVt3 group (P = .046). In addition, the A-M (n = 19) and I subgroups (n = 7) of PVt4 had worse prognoses than the PV0 or PVt3 groups (P = .005 and < .001, respectively). All patients in the I subgroup of PVt4 died within 9 months after resection. On multivariate analysis, PVt4 (P = .029) was identified as an independent prognostic factor. CONCLUSIONS: In perihilar cholangiocarcinoma, postoperative survival was no different between patients with and without ipsilateral portal vein invasion, although patients with tumor invasion to the main or contralateral branches of the portal vein, especially with tunica intima invasion, had extremely poor prognoses. PubMed","prediction_labels":"HUMAN"},{"cleaned":"splanchnic vein thrombosis cholangiocarcinoma retrospective observational study donostia university hospital introduction intra abdominalneoplasmsconstitutethemostimportantcauserelatedto splanchnicveinthrombotic stv events followedbycirrhosisandinflammatorybowel diseases svtisaheterogeneousillnessthatcouldaffecttheportalveinsystem hepatic veinsystem budd chiarisyndrome splenicveinsystemoruppermesentericveinsystem itisaninfrequentissuewithanincidenceof0 5 0 7 100 000patients year muchless frequentthandeepveinthrombosisevents itcanappearasymptomaticallyorwithdifferentsymptomsdependingonitslocalization ouraimwastodescribetheincidenceand characteristicsofsplanchnicveinthrombosiseventsinacohortofpatientsdiagnosedwith cholangiocarcinoma cca inourcenterfromjanuary2016tojune2018 methods data biliary tract cancer btc patients treated inour centerfrom january 2016tilljune 2018 collected performed aretrospectivesearch ofsvt cohort analysed data diagnosis treatment follow event results january 2016to june 2018a total 94 patientswere diagnosed btc center including intrahepatic cca icca perihilar cca pcca distal cca dcca ampuloma gallbladdercancer 15 patients presented ansvt event anincidence nearly 15 80 patients icca 20 pcca 67 patients metastatic disease 33 locally advanceddisease anyone 15 patients treated surgery 75 cases asymptomaticandallof diagnosed incidentally ctscan atthe sametime asthe primarytumour symptomatic ascites painwere frequent symptoms 50 patients treated low weight heparin stabilization thrombotic disease two needed dose reduction due tochemotherapy related thrombocytopenia however nocase thrombotic disease progression observed among patients notreceive anticoagulanttherapy refers tothe localization svt 80 events portal vein less frequently thrombosis affected suprahepatic vena cava conclusion best knowledge first report svt btc patients cohort 15 patientswith ccawere diagnosed asplanchnic thrombotic event locally advanced metastatic icca thrombotic event incidental findingat diagnosis behave asymptomatically exceptin fourpatientswho developedascites orpain indication benefit anticoagulation patients remains unclear treatment cancer complication evaluated prospective clinical trials google scholar","probabilities":0.9799733,"Title":"Splanchnic Vein Thrombosis In Cholangiocarcinoma A Retrospective Observational Study Donostia University Hospital","Abstract":"Introduction: Intra-abdominalneoplasmsconstitutethemostimportantcauserelatedto splanchnicveinthrombotic(STV)events,followedbycirrhosisandinflammatorybowel diseases.SVTisaheterogeneousillnessthatcouldaffecttheportalveinsystem,hepatic veinsystem(Budd-ChiariSyndrome),splenicveinsystemoruppermesentericveinsystem.Itisaninfrequentissuewithanincidenceof0.5-0.7/100.000patients/year,muchless frequentthandeepveinthrombosisevents.Itcanappearasymptomaticallyorwithdifferentsymptomsdependingonitslocalization.Ouraimwastodescribetheincidenceand characteristicsofsplanchnicveinthrombosiseventsinacohortofpatientsdiagnosedwith Cholangiocarcinoma(CCA)inourcenterfromJanuary2016toJune2018. Methods: Data from biliary tract cancer (BTC)patients treated inour centerfrom January 2016tillJune 2018 were collected. We performed aretrospectivesearch ofSVT in our cohort and analysed data about diagnosis, treatment and follow-up of this event. Results: From January 2016to June 2018a total of 94 patientswere diagnosed of BTC in our center, including intrahepatic CCA(iCCA), perihilar CCA(pCCA), distal CCA (dCCA), ampuloma and gallbladdercancer. 15 patients presented with anSVT event, anincidence of nearly 15%. 80% of those patients were iCCA and 20% were pCCA. 67% of the patients had metastatic disease and 33% had locally advanceddisease. Anyone of those 15 patients had been treated with surgery. 75% of the cases were asymptomaticandallof them were diagnosed incidentally by CTscan atthe sametime asthe primarytumour. When symptomatic, ascites and painwere the most frequent symptoms. 50% of the patients were treated with low weight heparin with a stabilization of the thrombotic disease;two of them needed dose reduction due tochemotherapy-related thrombocytopenia. However, nocase of thrombotic disease progression was observed among patients who did notreceive anticoagulanttherapy. When it refers tothe localization of the SVT, 80% of the events were in the portal vein. Less frequently thrombosis affected suprahepatic or vena cava. Conclusion: At the best of our knowledge, this is the first report about SVT in BTC patients. In our cohort, 15% of the patientswith CCAwere diagnosed with asplanchnic thrombotic event. Most of them were locally advanced or metastatic iCCA. Thrombotic event was an incidental findingat diagnosis and behave asymptomatically exceptin fourpatientswho developedascites orpain. Indication and benefit of anticoagulation in those patients remains unclear. Treatment of this cancer complication should be evaluated in prospective clinical trials.","Source":"Google Scholar","category":"HUMAN","training_data":"Splanchnic Vein Thrombosis In Cholangiocarcinoma A Retrospective Observational Study Donostia University Hospital Introduction: Intra-abdominalneoplasmsconstitutethemostimportantcauserelatedto splanchnicveinthrombotic(STV)events,followedbycirrhosisandinflammatorybowel diseases.SVTisaheterogeneousillnessthatcouldaffecttheportalveinsystem,hepatic veinsystem(Budd-ChiariSyndrome),splenicveinsystemoruppermesentericveinsystem.Itisaninfrequentissuewithanincidenceof0.5-0.7/100.000patients/year,muchless frequentthandeepveinthrombosisevents.Itcanappearasymptomaticallyorwithdifferentsymptomsdependingonitslocalization.Ouraimwastodescribetheincidenceand characteristicsofsplanchnicveinthrombosiseventsinacohortofpatientsdiagnosedwith Cholangiocarcinoma(CCA)inourcenterfromJanuary2016toJune2018. Methods: Data from biliary tract cancer (BTC)patients treated inour centerfrom January 2016tillJune 2018 were collected. We performed aretrospectivesearch ofSVT in our cohort and analysed data about diagnosis, treatment and follow-up of this event. Results: From January 2016to June 2018a total of 94 patientswere diagnosed of BTC in our center, including intrahepatic CCA(iCCA), perihilar CCA(pCCA), distal CCA (dCCA), ampuloma and gallbladdercancer. 15 patients presented with anSVT event, anincidence of nearly 15%. 80% of those patients were iCCA and 20% were pCCA. 67% of the patients had metastatic disease and 33% had locally advanceddisease. Anyone of those 15 patients had been treated with surgery. 75% of the cases were asymptomaticandallof them were diagnosed incidentally by CTscan atthe sametime asthe primarytumour. When symptomatic, ascites and painwere the most frequent symptoms. 50% of the patients were treated with low weight heparin with a stabilization of the thrombotic disease;two of them needed dose reduction due tochemotherapy-related thrombocytopenia. However, nocase of thrombotic disease progression was observed among patients who did notreceive anticoagulanttherapy. When it refers tothe localization of the SVT, 80% of the events were in the portal vein. Less frequently thrombosis affected suprahepatic or vena cava. Conclusion: At the best of our knowledge, this is the first report about SVT in BTC patients. In our cohort, 15% of the patientswith CCAwere diagnosed with asplanchnic thrombotic event. Most of them were locally advanced or metastatic iCCA. Thrombotic event was an incidental findingat diagnosis and behave asymptomatically exceptin fourpatientswho developedascites orpain. Indication and benefit of anticoagulation in those patients remains unclear. Treatment of this cancer complication should be evaluated in prospective clinical trials. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"hypoxia induced plod2 key regulator epithelial mesenchymal transition chemoresistance biliary tract cancer background prognosis biliary tract cancer btc unfavorable due chemoresistance hypoxia triggers epithelial mesenchymal transition emt closely related drug resistance study focused functional roles procollagen lysine 2 oxoglutarate 5 dioxygenase 2 plod2 hypoxia induced gene btc assessed clinical significance plod2 methods expression plod2 hypoxia assessed btc cell lines gemcitabine resistant gr btc cell lines transfected small interfering rna sirna plod2 emt markers chemoresistance evaluated plod2 expression also characterized using immunohistochemistry btc clinical specimens following resection patient survival analyzed role plod2 expression examined results expression plod2 induced hypoxia vitro upregulated btc gr cell lines low expression epithelial markers high expression mesenchymal markers downregulation plod2 sirna resulted improved chemoresistance recovery epithelial markers reduction mesenchymal markers resected btc samples plod2 expression significantly correlated lymph node metastasis p 0 037 stage p 0 001 recurrence free survival p 0 011 overall survival p 0 001 rates significantly lower patients high expression plod2 plod2 expression independent prognostic factor overall survival p 0 019 conclusions expression plod2 influenced chemoresistance emt high expression plod2 significant unfavorable prognostic factor btc patients plod2 might potential therapeutic target overcoming chemoresistance pubmed","probabilities":1.0,"Title":"Hypoxia-Induced PLOD2 is a Key Regulator in Epithelial-Mesenchymal Transition and Chemoresistance in Biliary Tract Cancer","Abstract":"BACKGROUND: The prognosis of biliary tract cancer (BTC) is unfavorable due to its chemoresistance. Hypoxia triggers epithelial-to-mesenchymal transition (EMT), which is closely related to drug resistance. In this study, we focused on the functional roles of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a hypoxia-induced gene, in BTC, and assessed the clinical significance of PLOD2. METHODS: The expression of PLOD2 under hypoxia was assessed in BTC cell lines. Gemcitabine-resistant (GR) BTC cell lines were transfected with small interfering RNA (siRNA) against PLOD2, and EMT markers and chemoresistance were evaluated. PLOD2 expression was also characterized using immunohistochemistry in BTC clinical specimens following resection. Patient survival was analyzed and the role of PLOD2 expression was examined. RESULTS: The expression of PLOD2 was induced by hypoxia in vitro and was upregulated in BTC-GR cell lines, which had low expression of epithelial markers and high expression of mesenchymal markers. Downregulation of PLOD2 by siRNA resulted in improved chemoresistance, recovery of epithelial markers, and reduction of mesenchymal markers. In the resected BTC samples, PLOD2 expression was significantly correlated with lymph node metastasis (p = 0.037) and stage (p = 0.001). Recurrence-free survival (p = 0.011) and overall survival (p < 0.001) rates were significantly lower in patients with high expression of PLOD2. PLOD2 expression was an independent prognostic factor for overall survival (p = 0.019). CONCLUSIONS: The expression of PLOD2 influenced chemoresistance through EMT, and high expression of PLOD2 was a significant unfavorable prognostic factor in BTC patients. PLOD2 might be a potential therapeutic target for overcoming chemoresistance.","Source":"PubMed","category":"HUMAN","training_data":"Hypoxia-Induced PLOD2 is a Key Regulator in Epithelial-Mesenchymal Transition and Chemoresistance in Biliary Tract Cancer BACKGROUND: The prognosis of biliary tract cancer (BTC) is unfavorable due to its chemoresistance. Hypoxia triggers epithelial-to-mesenchymal transition (EMT), which is closely related to drug resistance. In this study, we focused on the functional roles of procollagen-lysine, 2-oxoglutarate 5-dioxygenase 2 (PLOD2), a hypoxia-induced gene, in BTC, and assessed the clinical significance of PLOD2. METHODS: The expression of PLOD2 under hypoxia was assessed in BTC cell lines. Gemcitabine-resistant (GR) BTC cell lines were transfected with small interfering RNA (siRNA) against PLOD2, and EMT markers and chemoresistance were evaluated. PLOD2 expression was also characterized using immunohistochemistry in BTC clinical specimens following resection. Patient survival was analyzed and the role of PLOD2 expression was examined. RESULTS: The expression of PLOD2 was induced by hypoxia in vitro and was upregulated in BTC-GR cell lines, which had low expression of epithelial markers and high expression of mesenchymal markers. Downregulation of PLOD2 by siRNA resulted in improved chemoresistance, recovery of epithelial markers, and reduction of mesenchymal markers. In the resected BTC samples, PLOD2 expression was significantly correlated with lymph node metastasis (p = 0.037) and stage (p = 0.001). Recurrence-free survival (p = 0.011) and overall survival (p < 0.001) rates were significantly lower in patients with high expression of PLOD2. PLOD2 expression was an independent prognostic factor for overall survival (p = 0.019). CONCLUSIONS: The expression of PLOD2 influenced chemoresistance through EMT, and high expression of PLOD2 was a significant unfavorable prognostic factor in BTC patients. PLOD2 might be a potential therapeutic target for overcoming chemoresistance. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tricellulin expression prognostic significance primary liver carcinomas numerous data suggest altered expression tight junction proteins occludin claudins plays important role carcinogenesis however little known tricellulin transmembrane tight junction protein concentrated three epithelial cells meet aimed characterize tricellulin expression normal cirrhotic liver comparison primary hepatic neoplasms tricellulin expression 20 control livers 12 cirrhotic livers 32 hepatocellular carcinomas hcc 20 intrahepatic cholangiocarcinomas iccc investigated immunohistochemistry western blotting co localization tricellulin claudin 1 4 mrp2 studied using double immunofluorescence scattered tricellulin immunopositivity restricted biliary pole hepatocytes confirmed co localization mrp2 moreover spotted like reaction observed bile duct epithelial cells 40 hccs marked tricellulin overexpression measured regardless tumor grades icccs however tricellulin expression decreased parallel dedifferentiation hccs high tricellulin expression icccs low tricellulin expression correlated poor prognosis co localization mrp2 might substantiate tricellulin plays role blood biliary barrier overexpressed tricellulin subset hccs correlated unfavorable prognosis similar ductal pancreatic adenocarcinoma higher grades icccs associated decreased tricellulin expression correlating poor prognosis pubmed","probabilities":0.9799733,"Title":"Tricellulin expression and its prognostic significance in primary liver carcinomas","Abstract":"Numerous data suggest that altered expression of tight junction proteins such as occludin and claudins plays important role in carcinogenesis. However, little is known about tricellulin, a transmembrane tight junction protein concentrated where three epithelial cells meet. We aimed to characterize tricellulin expression in normal and cirrhotic liver in comparison to primary hepatic neoplasms. Tricellulin expression of 20 control livers, 12 cirrhotic livers, 32 hepatocellular carcinomas (HCC), and 20 intrahepatic cholangiocarcinomas (iCCC) was investigated by immunohistochemistry and Western blotting. Co-localization of tricellulin with claudin-1, -4, and MRP2 was studied using double immunofluorescence. Scattered tricellulin immunopositivity was restricted to biliary pole of hepatocytes confirmed by co-localization with MRP2. Moreover, spotted-like reaction was observed between bile duct epithelial cells. In 40 % of HCCs marked tricellulin overexpression was measured regardless of tumor grades. In iCCCs, however, tricellulin expression decreased parallel with dedifferentiation. In HCCs high tricellulin expression, in iCCCs low tricellulin expression correlated with poor prognosis. Co-localization with MRP2 might substantiate that tricellulin plays role in blood-biliary barrier. Overexpressed tricellulin in a subset of HCCs correlated with unfavorable prognosis. Similar to ductal pancreatic adenocarcinoma, higher grades of iCCCs were associated with decreased tricellulin expression correlating with poor prognosis.","Source":"PubMed","category":"ANIMAL","training_data":"Tricellulin expression and its prognostic significance in primary liver carcinomas Numerous data suggest that altered expression of tight junction proteins such as occludin and claudins plays important role in carcinogenesis. However, little is known about tricellulin, a transmembrane tight junction protein concentrated where three epithelial cells meet. We aimed to characterize tricellulin expression in normal and cirrhotic liver in comparison to primary hepatic neoplasms. Tricellulin expression of 20 control livers, 12 cirrhotic livers, 32 hepatocellular carcinomas (HCC), and 20 intrahepatic cholangiocarcinomas (iCCC) was investigated by immunohistochemistry and Western blotting. Co-localization of tricellulin with claudin-1, -4, and MRP2 was studied using double immunofluorescence. Scattered tricellulin immunopositivity was restricted to biliary pole of hepatocytes confirmed by co-localization with MRP2. Moreover, spotted-like reaction was observed between bile duct epithelial cells. In 40 % of HCCs marked tricellulin overexpression was measured regardless of tumor grades. In iCCCs, however, tricellulin expression decreased parallel with dedifferentiation. In HCCs high tricellulin expression, in iCCCs low tricellulin expression correlated with poor prognosis. Co-localization with MRP2 might substantiate that tricellulin plays role in blood-biliary barrier. Overexpressed tricellulin in a subset of HCCs correlated with unfavorable prognosis. Similar to ductal pancreatic adenocarcinoma, higher grades of iCCCs were associated with decreased tricellulin expression correlating with poor prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"suppression stat3 reduces il 6 induced cell migration cholangiocarcinoma cell lines properly copy pasted go link click p 2113 google scholar","probabilities":0.9467213,"Title":"Suppression Of Stat3 Reduces Il-6-Induced Cell Migration Of Cholangiocarcinoma Cell Lines","Abstract":"Cannot be properly copy-pasted. Go through the link Click P-2113","Source":"Google Scholar","category":"ANIMAL","training_data":"Suppression Of Stat3 Reduces Il-6-Induced Cell Migration Of Cholangiocarcinoma Cell Lines Cannot be properly copy-pasted. Go through the link Click P-2113 Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"fourteen year surgical experience gallbladder cancer validity curative resection affecting survival background aims early diagnosis r0 resection gallbladder cancer offer chance cure aims retrospective study determine clinicopathologic prognostic factors affecting survival recurrence methodology 1995 2008 total 69 patients gallbladder cancer underwent surgical exploration resection reviewed retrospectively results 69 patients 34 achieved r0 resection 49 3 overall survival rates 36 6 3 years 24 4 5 years multivariate analysis overall survival demonstrated non r0 resection lymph node dissection infiltrative tumors moderate poor differentiation depth invasion significant independent predictors poor prognosis recurrence occurred 21 patients seventh edition american joint committee cancer staging system provided relatively better prediction survival patients gallbladder cancer conclusions r0 resection lymph node dissection important surgical strategy improve overall survival infiltrative tumor independent prognostic factor disease free survival pubmed","probabilities":0.9799733,"Title":"Fourteen year surgical experience of gallbladder cancer: validity of curative resection affecting survival","Abstract":"BACKGROUND/AIMS: Early diagnosis and R0 resection of gallbladder cancer offer a chance for cure. The aims of this retrospective study were to determine the clinicopathologic prognostic factors affecting survival and recurrence. METHODOLOGY: Between 1995 and 2008, a total of 69 patients with gallbladder cancer who underwent surgical exploration or resection were reviewed retrospectively. RESULTS: Of the 69 patients, 34 achieved R0 resection (49.3%). The overall survival rates were 36.6% at 3 years and 24.4 % at 5 years. Multivariate analysis for overall survival demonstrated that non-R0 resection, lymph node dissection, infiltrative tumors, moderate to poor differentiation and depth of invasion were significant independent predictors of poor prognosis. Recurrence occurred in 21 patients. The seventh edition of American Joint Committee on Cancer staging system provided relatively better prediction of survival in patients with gallbladder cancer. CONCLUSIONS: R0 resection and lymph node dissection is an important surgical strategy to improve overall survival. Infiltrative tumor was an independent prognostic factor for disease free survival.","Source":"PubMed","category":"HUMAN","training_data":"Fourteen year surgical experience of gallbladder cancer: validity of curative resection affecting survival BACKGROUND/AIMS: Early diagnosis and R0 resection of gallbladder cancer offer a chance for cure. The aims of this retrospective study were to determine the clinicopathologic prognostic factors affecting survival and recurrence. METHODOLOGY: Between 1995 and 2008, a total of 69 patients with gallbladder cancer who underwent surgical exploration or resection were reviewed retrospectively. RESULTS: Of the 69 patients, 34 achieved R0 resection (49.3%). The overall survival rates were 36.6% at 3 years and 24.4 % at 5 years. Multivariate analysis for overall survival demonstrated that non-R0 resection, lymph node dissection, infiltrative tumors, moderate to poor differentiation and depth of invasion were significant independent predictors of poor prognosis. Recurrence occurred in 21 patients. The seventh edition of American Joint Committee on Cancer staging system provided relatively better prediction of survival in patients with gallbladder cancer. CONCLUSIONS: R0 resection and lymph node dissection is an important surgical strategy to improve overall survival. Infiltrative tumor was an independent prognostic factor for disease free survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"national trends management survival surgically managed gallbladder adenocarcinoma 15 years population based analysis introduction national comprehensive cancer network nccn guidelines recommend hepatic resection lymphadenectomy lnd gallbladder adenocarcinoma gba sought evaluate compliance recommendations assess trends management survival patients gba methods using surveillance epidemiology end results seer medicare linked data identified 2 955 patients gba underwent cancer directed surgery 1991 2005 assessed clinicopathologic data trends surgical management survival results 1991 2005 preoperative evaluation included ct 62 mri 6 pet 2 383 13 patients underwent radical resection hepatectomy temporal increase study period 1991 1995 12 1996 1999 10 2000 2002 12 0 2003 2005 16 p 0 001 patients undergoing radical resection hepatectomy lnd 3 nodes performed 96 3 patients among patients lnd 47 nodal metastasis overall 1 3 5 year survival 56 30 21 multivariate analysis radical resection hepatectomy hazard ratio hr 0 71 lnd 3 nodes hr 0 56 independently associated increased survival significant improvement survival time p 0 60 conclusions compliance nccn guidelines gba remains poor survival patients surgically managed gba improved time pubmed","probabilities":0.9799733,"Title":"National trends in the management and survival of surgically managed gallbladder adenocarcinoma over 15 years: a population-based analysis","Abstract":"INTRODUCTION: National Comprehensive Cancer Network (NCCN) guidelines recommend hepatic resection and lymphadenectomy (LND) for gallbladder adenocarcinoma (GBA). We sought to evaluate compliance with these recommendations and to assess trends in the management and survival of patients with GBA. METHODS: Using Surveillance, Epidemiology and End Results (SEER)-Medicare-linked data, we identified 2,955 patients with GBA who underwent cancer-directed surgery from 1991 to 2005. We assessed clinicopathologic data, trends in surgical management, and survival. RESULTS: From 1991 to 2005, preoperative evaluation included CT (62%), MRI (6%), and PET (2%). Only 383 (13%) patients underwent radical resection/hepatectomy with a temporal increase over the study period (1991-1995, 12%; 1996-1999, 10%; 2000-2002, 12.0%; 2003-2005, 16%; P < 0.001). For patients undergoing radical resection/hepatectomy, LND ≥ 3 nodes was performed in 96 (3%) patients. Among patients who had LND, 47% had nodal metastasis. The overall 1-, 3-, and 5-year survival was 56%, 30%, and 21%. On multivariate analysis, radical resection/hepatectomy (hazard ratio (HR) = 0.71) and LND ≥ 3 nodes (HR = 0.56) were independently associated with increased survival. There was no significant improvement in survival over time (P = 0.60). CONCLUSIONS: Compliance with NCCN guidelines for GBA remains poor. Survival of patients with surgically managed GBA has not improved over time.","Source":"PubMed","category":"HUMAN","training_data":"National trends in the management and survival of surgically managed gallbladder adenocarcinoma over 15 years: a population-based analysis INTRODUCTION: National Comprehensive Cancer Network (NCCN) guidelines recommend hepatic resection and lymphadenectomy (LND) for gallbladder adenocarcinoma (GBA). We sought to evaluate compliance with these recommendations and to assess trends in the management and survival of patients with GBA. METHODS: Using Surveillance, Epidemiology and End Results (SEER)-Medicare-linked data, we identified 2,955 patients with GBA who underwent cancer-directed surgery from 1991 to 2005. We assessed clinicopathologic data, trends in surgical management, and survival. RESULTS: From 1991 to 2005, preoperative evaluation included CT (62%), MRI (6%), and PET (2%). Only 383 (13%) patients underwent radical resection/hepatectomy with a temporal increase over the study period (1991-1995, 12%; 1996-1999, 10%; 2000-2002, 12.0%; 2003-2005, 16%; P < 0.001). For patients undergoing radical resection/hepatectomy, LND ≥ 3 nodes was performed in 96 (3%) patients. Among patients who had LND, 47% had nodal metastasis. The overall 1-, 3-, and 5-year survival was 56%, 30%, and 21%. On multivariate analysis, radical resection/hepatectomy (hazard ratio (HR) = 0.71) and LND ≥ 3 nodes (HR = 0.56) were independently associated with increased survival. There was no significant improvement in survival over time (P = 0.60). CONCLUSIONS: Compliance with NCCN guidelines for GBA remains poor. Survival of patients with surgically managed GBA has not improved over time. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radiation therapy biliary tract tumors joint experience three centers background aim study presents joint experience three centers treatment patients biliary tract tumors radiation therapy rt materials methods records 27 patients retrospectively reviewed patients undergone surgical resection received postoperative adjuvant rt whereas patients undergone surgical resection received rt palliative intent twenty patients adequate performance status treated rt chemotherapy remaining seven patients treated rt alone results follow ranged 1 44 months local control achieved 10 11 patients received rt palliative intent systemic failure observed eight patients 5 16 months fifteen patients died due disease related causes 1 22 months 2 years overall survival 33 disease free survival 19 surgical resection curative intent predicted improved local failure free survival improved disease free survival conclusion since local recurrence still leading cause failure following postoperative rt outcome following palliative rt far satisfactory indications target volume doses rt reconsidered pubmed","probabilities":0.9799733,"Title":"Radiation therapy for biliary tract tumors: the joint experience of three centers","Abstract":"BACKGROUND/AIM: This study presents the joint experience of three centers in the treatment of patients with biliary tract tumors with radiation therapy (RT). MATERIALS AND METHODS: The records of 27 patients were retrospectively reviewed. All of the patients who had undergone surgical resection received postoperative adjuvant RT, whereas all of the patients who had not undergone a surgical resection received RT with palliative intent. Twenty patients with adequate performance status were treated with RT and chemotherapy, while the remaining seven patients were treated with RT alone. RESULTS: Follow-up ranged from 1 to 44 months. Local control was not achieved in 10 out of 11 patients who had received RT with palliative intent. Systemic failure was observed in eight patients at 5 to 16 months. Fifteen patients died due to disease-related causes at 1 to 22 months. At 2 years, overall survival was 33% and disease-free survival was 19%. A surgical resection with curative intent predicted improved local failure-free survival and improved disease-free survival. CONCLUSION: Since local recurrence is still the leading cause of failure following postoperative RT and the outcome following palliative RT is far from satisfactory, the indications, the target volume, and the doses for RT should be reconsidered.","Source":"PubMed","category":"HUMAN","training_data":"Radiation therapy for biliary tract tumors: the joint experience of three centers BACKGROUND/AIM: This study presents the joint experience of three centers in the treatment of patients with biliary tract tumors with radiation therapy (RT). MATERIALS AND METHODS: The records of 27 patients were retrospectively reviewed. All of the patients who had undergone surgical resection received postoperative adjuvant RT, whereas all of the patients who had not undergone a surgical resection received RT with palliative intent. Twenty patients with adequate performance status were treated with RT and chemotherapy, while the remaining seven patients were treated with RT alone. RESULTS: Follow-up ranged from 1 to 44 months. Local control was not achieved in 10 out of 11 patients who had received RT with palliative intent. Systemic failure was observed in eight patients at 5 to 16 months. Fifteen patients died due to disease-related causes at 1 to 22 months. At 2 years, overall survival was 33% and disease-free survival was 19%. A surgical resection with curative intent predicted improved local failure-free survival and improved disease-free survival. CONCLUSION: Since local recurrence is still the leading cause of failure following postoperative RT and the outcome following palliative RT is far from satisfactory, the indications, the target volume, and the doses for RT should be reconsidered. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic accuracy seventh edition tnm classification compared fifth sixth edition distal cholangiocarcinoma background tnm classification distal cholangiocarcinoma first introduced 7th edition published 2009 however prognostic accuracy compared 5th 6th editions yet evaluated requires validation methods prospective histological database patients distal bile duct cancer analyzed histological parameters stage distal cholangiocarcinoma assessed according 5th 6th 7th editions tnm classification results 1994 2012 total 516 patients underwent pancreatic head resection 59 patients 11 4 experienced histologically confirmed distal cholangiocarcinoma median overall survival time 22 2 months 13 1 31 4 tumor recurrence occurred 23 patients median disease free survival time 14 1 months 7th edition showed monotonicity gradients stepwise increase mortality related stepwise increase tumor stage log rank test p 0 05 demonstrating best discrimination tested editions area receiver operating characteristic curve auc 0 82 95 ci 0 70 0 95 p 0 012 discrimination rate low 5th auc 0 67 95 ci 0 42 0 91 p 0 18 6th editions auc 0 70 95 ci 0 47 0 93 p 0 11 log rank test reach statistical significance multivariate analysis lymph node involvement positive resection margins positive independent predictors inferior survival p 0 05 conclusions 7th edition tnm classification favorable terms predicting outcome generated monotonicity grades strikingly 7th edition 5th 6th editions prognostic significance predict outcome pubmed","probabilities":0.9799733,"Title":"Prognostic Accuracy of the Seventh Edition of the TNM Classification Compared with the Fifth and Sixth Edition for Distal Cholangiocarcinoma","Abstract":"BACKGROUND: The TNM classification for distal cholangiocarcinoma was first introduced in the 7th edition, which was published in 2009; however, prognostic accuracy compared with the 5th and 6th editions has not yet been evaluated and requires validation. METHODS: A prospective histological database of patients with distal bile duct cancer was analyzed, and histological parameters and stage of the distal cholangiocarcinoma were assessed according to the 5th, 6th, and 7th editions of the TNM classification. RESULTS: Between 1994 and 2012, a total of 516 patients underwent pancreatic head resection, of whom 59 patients (11.4 %) experienced histologically confirmed distal cholangiocarcinoma. The median overall survival time was 22.2 months (13.1-31.4). Tumor recurrence occurred in 23 patients after a median disease-free survival time of 14.1 months. The 7th edition showed a monotonicity of all gradients, with a stepwise increase of mortality related to a stepwise increase of tumor stage (log-rank test; p < 0.05) demonstrating best discrimination of all tested editions [area under the receiver operating characteristic curve (AUC) 0.82; 95 % CI 0.70-0.95; p = 0.012]. The discrimination rate was low for the 5th (AUC 0.67; 95 % CI 0.42-0.91; p = 0.18) and 6th editions (AUC 0.70; 95 % CI 0.47-0.93; p = 0.11), while the log-rank test did not reach statistical significance. On multivariate analysis, lymph node involvement and positive resection margins were positive and independent predictors of inferior survival (p < 0.05). CONCLUSIONS: The 7th edition of the TNM classification was favorable in terms of predicting outcome, and generated a monotonicity of all grades. Strikingly, the 7th edition, but not the 5th and 6th editions, was of prognostic significance to predict outcome.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Accuracy of the Seventh Edition of the TNM Classification Compared with the Fifth and Sixth Edition for Distal Cholangiocarcinoma BACKGROUND: The TNM classification for distal cholangiocarcinoma was first introduced in the 7th edition, which was published in 2009; however, prognostic accuracy compared with the 5th and 6th editions has not yet been evaluated and requires validation. METHODS: A prospective histological database of patients with distal bile duct cancer was analyzed, and histological parameters and stage of the distal cholangiocarcinoma were assessed according to the 5th, 6th, and 7th editions of the TNM classification. RESULTS: Between 1994 and 2012, a total of 516 patients underwent pancreatic head resection, of whom 59 patients (11.4 %) experienced histologically confirmed distal cholangiocarcinoma. The median overall survival time was 22.2 months (13.1-31.4). Tumor recurrence occurred in 23 patients after a median disease-free survival time of 14.1 months. The 7th edition showed a monotonicity of all gradients, with a stepwise increase of mortality related to a stepwise increase of tumor stage (log-rank test; p < 0.05) demonstrating best discrimination of all tested editions [area under the receiver operating characteristic curve (AUC) 0.82; 95 % CI 0.70-0.95; p = 0.012]. The discrimination rate was low for the 5th (AUC 0.67; 95 % CI 0.42-0.91; p = 0.18) and 6th editions (AUC 0.70; 95 % CI 0.47-0.93; p = 0.11), while the log-rank test did not reach statistical significance. On multivariate analysis, lymph node involvement and positive resection margins were positive and independent predictors of inferior survival (p < 0.05). CONCLUSIONS: The 7th edition of the TNM classification was favorable in terms of predicting outcome, and generated a monotonicity of all grades. Strikingly, the 7th edition, but not the 5th and 6th editions, was of prognostic significance to predict outcome. PubMed","prediction_labels":"HUMAN"},{"cleaned":"racial ethnic disparities incidence survival intrahepatic cholangiocarcinoma icca united states abstract available google scholar","probabilities":0.9799733,"Title":"Racial And Ethnic Disparities In Incidence And Survival From Intrahepatic Cholangiocarcinoma (Icca) In The United States","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Racial And Ethnic Disparities In Incidence And Survival From Intrahepatic Cholangiocarcinoma (Icca) In The United States Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"impact skeletal muscle mass muscle quality visceral adiposity outcomes following resection intrahepatic cholangiocarcinoma background decrease skeletal muscle mass function known sarcopenia associated poor prognosis visceral fat accumulation also related mortality study investigated impact preoperative skeletal muscle mass muscle quality visceral adiposity outcomes patients undergoing resection intrahepatic cholangiocarcinoma icc methods retrospective analysis performed 109 patients undergoing resections icc january 2004 april 2015 skeletal muscle mass skeletal muscle index smi skeletal muscle quality muscle attenuation ma visceral adiposity visceral subcutaneous adipose tissue area ratio vsr measured preoperative computed tomography images impacts parameters outcomes icc resections analyzed results overall survival rates significantly lower patients low smi p 0 002 low ma p 0 032 high vsr p 0 026 compared patients high smi high ma low vsr respectively multivariate analyses patients stage iii low smi hazard ratio hr 3 29 p 0 003 low ma hr 2 86 p 0 010 revealed independent significant risk factors mortality patients stage iv none parameters identified risk factors absence adjuvant chemotherapy identified independent risk factor mortality hr 5 92 p 0 001 conclusions although stage important factor low skeletal muscle mass quality closely related mortality resection icc patients stage iii pubmed","probabilities":0.7966102,"Title":"Impact of Skeletal Muscle Mass, Muscle Quality, and Visceral Adiposity on Outcomes Following Resection of Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: Decrease in skeletal muscle mass and function, known as sarcopenia, is associated with poor prognosis. Visceral fat accumulation also is related to mortality. This study investigated the impact of preoperative skeletal muscle mass, muscle quality, and visceral adiposity on outcomes in patients undergoing resection of intrahepatic cholangiocarcinoma (ICC). METHODS: A retrospective analysis was performed of 109 patients undergoing resections of ICC between January 2004 and April 2015. Skeletal muscle mass [skeletal muscle index (SMI)], skeletal muscle quality [muscle attenuation (MA)], and visceral adiposity [visceral to subcutaneous adipose tissue area ratio (VSR)] were measured on preoperative computed tomography images. The impacts of these parameters on outcomes after ICC resections were analyzed. RESULTS: The overall survival rates were significantly lower in patients with low SMI (P = 0.002), low MA (P = 0.032), and high VSR (P = 0.026) compared with patients with high SMI, high MA, and low VSR, respectively. With multivariate analyses, in patients with stage I-III, low SMI (hazard ratio (HR) 3.29, P = 0.003) and low MA (HR 2.86, P = 0.010) were revealed as independent significant risk factors for mortality. In patients with stage IV, none of these parameters was identified as risk factors, with only the absence of adjuvant chemotherapy identified as an independent risk factor for mortality (HR 5.92, P = 0.001). CONCLUSIONS: Although stage was the most important factor, low skeletal muscle mass and quality were closely related to mortality after resection of ICC in patients with stage I-III.","Source":"PubMed","category":"HUMAN","training_data":"Impact of Skeletal Muscle Mass, Muscle Quality, and Visceral Adiposity on Outcomes Following Resection of Intrahepatic Cholangiocarcinoma BACKGROUND: Decrease in skeletal muscle mass and function, known as sarcopenia, is associated with poor prognosis. Visceral fat accumulation also is related to mortality. This study investigated the impact of preoperative skeletal muscle mass, muscle quality, and visceral adiposity on outcomes in patients undergoing resection of intrahepatic cholangiocarcinoma (ICC). METHODS: A retrospective analysis was performed of 109 patients undergoing resections of ICC between January 2004 and April 2015. Skeletal muscle mass [skeletal muscle index (SMI)], skeletal muscle quality [muscle attenuation (MA)], and visceral adiposity [visceral to subcutaneous adipose tissue area ratio (VSR)] were measured on preoperative computed tomography images. The impacts of these parameters on outcomes after ICC resections were analyzed. RESULTS: The overall survival rates were significantly lower in patients with low SMI (P = 0.002), low MA (P = 0.032), and high VSR (P = 0.026) compared with patients with high SMI, high MA, and low VSR, respectively. With multivariate analyses, in patients with stage I-III, low SMI (hazard ratio (HR) 3.29, P = 0.003) and low MA (HR 2.86, P = 0.010) were revealed as independent significant risk factors for mortality. In patients with stage IV, none of these parameters was identified as risk factors, with only the absence of adjuvant chemotherapy identified as an independent risk factor for mortality (HR 5.92, P = 0.001). CONCLUSIONS: Although stage was the most important factor, low skeletal muscle mass and quality were closely related to mortality after resection of ICC in patients with stage I-III. PubMed","prediction_labels":"HUMAN"},{"cleaned":"low incidence lymph node metastasis resection hepatitis virus related intrahepatic cholangiocarcinoma background objectives determined rates initial lymph node metastasis following curative resection mass forming type intrahepatic cholangiocarcinoma icc patients without hepatitis virus infection methods enrolled 87 patients january 2000 december 2013 icc without preoperative lymph node metastasis without lymph node dissection patients included 32 seropositive hepatitis b c virus virus group 55 evidence hepatitis virus infection nonvirus group postsurgical outcomes initial recurrence groups compared identified risk factors lymph node metastasis initial recurrence results platelet counts prothrombin activities significantly lower virus group compared nonvirus group number patients chronic hepatitis liver cirrhosis significantly higher virus group compared nonvirus group well respective rates recurrence free survival one patient 3 virus group 14 patients 25 nonvirus group lymph node metastasis initial recurrence p 0 007 multivariate analysis revealed absence hepatitis virus infection independent risk factor p 0 047 conclusion hepatitis virus associated mass forming type icc confers low risk lymph node metastasis initial postoperative recurrence stn","probabilities":0.9799733,"Title":"Low Incidence Of Lymph Node Metastasis After Resection Of Hepatitis Virus-Related Intrahepatic Cholangiocarcinoma","Abstract":"Background and objectives: We determined the rates of initial lymph node metastasis following curative resection of mass-forming type-intrahepatic cholangiocarcinoma (ICC) in patients with and without hepatitis virus infection. \r\n\r\n Methods: We enrolled 87 patients between January 2000 and December 2013 with ICC without preoperative lymph node metastasis and without lymph node dissection. Patients included 32 who were seropositive for hepatitis B or C virus (virus group) and 55 who had no evidence of hepatitis virus infection (nonvirus group). Postsurgical outcomes and initial recurrence of the groups were compared, and we identified the risk factors for lymph node metastasis as initial recurrence. \r\n\r\n Results: Platelet counts and prothrombin activities were significantly lower in the virus group compared with those of the nonvirus group. The number of patients with chronic hepatitis or liver cirrhosis was significantly higher in the virus group compared with the nonvirus group as well as their respective rates of recurrence-free survival. One patient (3%) in the virus group and 14 patients (25%) in the nonvirus group had lymph node metastasis as initial recurrence (p = 0.007). Multivariate analysis revealed that the absence of hepatitis virus infection as an independent risk factor (p = 0.047). \r\n\r\n Conclusion: Hepatitis virus-associated mass-forming-type ICC confers a low risk of lymph node metastasis as initial postoperative recurrence.","Source":"STN","category":"HUMAN","training_data":"Low Incidence Of Lymph Node Metastasis After Resection Of Hepatitis Virus-Related Intrahepatic Cholangiocarcinoma Background and objectives: We determined the rates of initial lymph node metastasis following curative resection of mass-forming type-intrahepatic cholangiocarcinoma (ICC) in patients with and without hepatitis virus infection. \r\n\r\n Methods: We enrolled 87 patients between January 2000 and December 2013 with ICC without preoperative lymph node metastasis and without lymph node dissection. Patients included 32 who were seropositive for hepatitis B or C virus (virus group) and 55 who had no evidence of hepatitis virus infection (nonvirus group). Postsurgical outcomes and initial recurrence of the groups were compared, and we identified the risk factors for lymph node metastasis as initial recurrence. \r\n\r\n Results: Platelet counts and prothrombin activities were significantly lower in the virus group compared with those of the nonvirus group. The number of patients with chronic hepatitis or liver cirrhosis was significantly higher in the virus group compared with the nonvirus group as well as their respective rates of recurrence-free survival. One patient (3%) in the virus group and 14 patients (25%) in the nonvirus group had lymph node metastasis as initial recurrence (p = 0.007). Multivariate analysis revealed that the absence of hepatitis virus infection as an independent risk factor (p = 0.047). \r\n\r\n Conclusion: Hepatitis virus-associated mass-forming-type ICC confers a low risk of lymph node metastasis as initial postoperative recurrence. STN","prediction_labels":"HUMAN"},{"cleaned":"liver transplantation cholangiocarcinoma selection essential acceptable results background aims cholangiocarcinoma cca considered contraindication liver transplantation liver transplant centers aim study report results well explore factors influence patient survival liver transplantation cca patients transplant patients cca norway sweden finland 1984 2005 included n 53 thirty three patients 62 intrahepatic cca twenty one patients 40 advanced tumor tnm stage 2 thirty four 53 recipients 64 primary sclerosing cholangitis psc results patients tnm stage 2 transplanted 1995 5 year survival rate 48 overall 5 year patient survival rate 25 difference survival patients extrahepatic intrahepatic cca 5 year survival rate among patients tnm stage 2 36 patients tnm stage 2 10 5 year survival rate difference significant p 0 01 patients transplanted 1995 significantly better 5 year survival rate pre 1995 patients 38 vs 0 p 0 01 patients transplanted 1995 tnm 2 ca 19 9 100 5 year survival 58 conclusion selecting cca patients tnm stage 2 ca 19 9 100 reasonable 5 year survival rate possible think cca selected cases acceptable indication liver transplantation pubmed","probabilities":0.9799733,"Title":"Liver transplantation for cholangiocarcinoma: selection is essential for acceptable results","Abstract":"BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is considered a contraindication for liver transplantation by most liver transplant centers. The aim of this study has been to report our results as well as to explore factors that influence patient survival after liver transplantation for CCA. PATIENTS: All transplant patients with CCA in Norway, Sweden and Finland during 1984-2005 were included (n = 53). Thirty-three patients (62%) had intrahepatic CCA. Twenty-one patients (40%) had a more advanced tumor (>TNM stage 2). Thirty-four of the 53 recipients (64%) had primary sclerosing cholangitis (PSC). RESULTS: Patients with TNM stage ≤ 2 transplanted after 1995 had a 5-year survival rate of 48%. The overall 5-year patient survival rate was 25%. There was no difference in survival between patients with extrahepatic and intrahepatic CCA. The 5-year survival rate among patients with TNM stage ≤ 2 was 36%. Patients with TNM stage >2 had a 10% 5-year survival rate; the difference was significant at p < 0.01. Patients transplanted after 1995 had a significantly better 5-year survival rate than pre-1995 patients (38% vs. 0%, p < 0.01). Patients transplanted after 1995 with TNM ≤ 2 and CA 19-9 ≤ 100 had the 5-year survival of 58%. CONCLUSION: By selecting CCA patients with TNM stage ≤ 2 and a CA 19-9 ≤ 100 a reasonable 5-year survival rate is possible. We think that CCA in selected cases can be an acceptable indication for liver transplantation.","Source":"PubMed","category":"HUMAN","training_data":"Liver transplantation for cholangiocarcinoma: selection is essential for acceptable results BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is considered a contraindication for liver transplantation by most liver transplant centers. The aim of this study has been to report our results as well as to explore factors that influence patient survival after liver transplantation for CCA. PATIENTS: All transplant patients with CCA in Norway, Sweden and Finland during 1984-2005 were included (n = 53). Thirty-three patients (62%) had intrahepatic CCA. Twenty-one patients (40%) had a more advanced tumor (>TNM stage 2). Thirty-four of the 53 recipients (64%) had primary sclerosing cholangitis (PSC). RESULTS: Patients with TNM stage ≤ 2 transplanted after 1995 had a 5-year survival rate of 48%. The overall 5-year patient survival rate was 25%. There was no difference in survival between patients with extrahepatic and intrahepatic CCA. The 5-year survival rate among patients with TNM stage ≤ 2 was 36%. Patients with TNM stage >2 had a 10% 5-year survival rate; the difference was significant at p < 0.01. Patients transplanted after 1995 had a significantly better 5-year survival rate than pre-1995 patients (38% vs. 0%, p < 0.01). Patients transplanted after 1995 with TNM ≤ 2 and CA 19-9 ≤ 100 had the 5-year survival of 58%. CONCLUSION: By selecting CCA patients with TNM stage ≤ 2 and a CA 19-9 ≤ 100 a reasonable 5-year survival rate is possible. We think that CCA in selected cases can be an acceptable indication for liver transplantation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value fdg pet ct total lesion glycolysis patients resectable distal bile duct adenocarcinoma aim investigated prognostic value clinicopathological factors patients distal bile duct adenocarcinoma curative resection patients methods retrospective study included 25 patients underwent 18 f fluorodeoxyglucose positron emission tomography computed tomography fdg pet ct surgery maximum standardized uptake value suvmax metabolic tumor volume mtv total lesion glycolysis tlg measured using fdg pet ct fdg pet ct parameters clinicopathological factors assessed evaluate survival results univariate survival analysis showed high tlg high mtv high suvmax significant prognostic predictors poor overall survival progression free survival high tlg large tumor size significant predictors poor prognosis multivariate survival analysis high tlg independent prognostic predictor poor overall survival p 0 025 conclusion preoperative assessment tlg fdg pet ct might useful prognostic predictor patients distal bile duct adenocarcinoma curative resection pubmed","probabilities":0.9799733,"Title":"Prognostic Value of FDG-PET/CT Total Lesion Glycolysis for Patients with Resectable Distal Bile Duct Adenocarcinoma","Abstract":"AIM: We investigated the prognostic value of clinicopathological factors in patients with a distal bile duct adenocarcinoma after curative resection. PATIENTS AND METHODS: This retrospective study included 25 patients who underwent (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) before surgery. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using FDG-PET/CT. FDG-PET/CT parameters and other clinicopathological factors were assessed to evaluate survival. RESULTS: Univariate survival analysis showed that high TLG, high MTV, and high SUVmax were significant prognostic predictors for poor overall survival. For progression-free survival, high TLG and large tumor size were significant predictors for a poor prognosis. After multivariate survival analysis, only high TLG was an independent prognostic predictor for poor overall survival (p=0.025). CONCLUSION: Preoperative assessment of TLG by FDG-PET/CT might be a useful prognostic predictor in patients with a distal bile duct adenocarcinoma after curative resection.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Value of FDG-PET/CT Total Lesion Glycolysis for Patients with Resectable Distal Bile Duct Adenocarcinoma AIM: We investigated the prognostic value of clinicopathological factors in patients with a distal bile duct adenocarcinoma after curative resection. PATIENTS AND METHODS: This retrospective study included 25 patients who underwent (18)F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG-PET/CT) before surgery. The maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured using FDG-PET/CT. FDG-PET/CT parameters and other clinicopathological factors were assessed to evaluate survival. RESULTS: Univariate survival analysis showed that high TLG, high MTV, and high SUVmax were significant prognostic predictors for poor overall survival. For progression-free survival, high TLG and large tumor size were significant predictors for a poor prognosis. After multivariate survival analysis, only high TLG was an independent prognostic predictor for poor overall survival (p=0.025). CONCLUSION: Preoperative assessment of TLG by FDG-PET/CT might be a useful prognostic predictor in patients with a distal bile duct adenocarcinoma after curative resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival trends chemorefractory unresectable intrahepatic cholangiocarcinoma icc effect yttrium 90 y90 radioembolization seer versus tertiary cancer center background survival patients chemorefractory unresectable icc treated y90 radioembolization vs best supportive care investigated large scale population studies methods irb approval institute cancer registry queried y90 treated patients chemorefractory unresectable icc diagnosed jan 2002 nov 2011 eighteen registries u surveillance epidemiology end results seer database queried patients advanced icc amenable surgery radiation diagnosed period baseline characteristics median overall survival os icc diagnosis median os first y90 stratified national state cohorts survival analysis 95 confidence intervals ci calculated using kaplan meier estimation results total 24 patients received y90 therapy chemorefractory unresectable icc group 2757 patients unresectable icc received neither radiation cancer directed surgery group b included groups similar mean age diagnosis gender race bilobar disease portal vein thrombosis mean largest tumor size p 0 05 median os icc diagnosis 20 8 months group 95 ci 11 2 30 5 3 0 months group b 95 ci 2 7 3 3 p 0 001 median os first y90 11 5 months group 95 ci 4 8 18 2 interval survival rates icc diagnosis group vs b 100 vs 77 1 month 100 vs 63 3 months 92 vs 30 6 months 67 vs 17 1 year 42 vs 6 2 years 17 vs 3 3 years conclusions y90 radioembolization patients chemorefractory unresectable icc demonstrated significantly greater median os favorable long term survival rates compared best supportive care google scholar","probabilities":0.9799733,"Title":"Survival Trends In Chemorefractory Unresectable Intrahepatic Cholangiocarcinoma (Icc) And The Effect Of Yttrium-90 (Y90) Radioembolization: Seer Versus Tertiary Cancer Center","Abstract":"Background: Survival in patients with chemorefractory unresectable ICC treated with Y90 radioembolization vs. best supportive care has not been investigated in large-scale population studies. Methods: Under IRB approval, our institute’s cancer registry was queried for Y90-treated patients with chemorefractory unresectable ICC diagnosed from Jan 2002 to Nov 2011. Eighteen registries of U.S. Surveillance, Epidemiology and End Results (SEER) database were queried for patients with advanced ICC not amenable to surgery/radiation diagnosed in the same period. Baseline characteristics, median overall survival (OS) from ICC diagnosis and median OS from first Y90 were stratified by national/state cohorts. Survival analysis and 95% confidence intervals (CI) were calculated using Kaplan-Meier estimation. Results: A total of 24 patients who received Y90 therapy for chemorefractory unresectable ICC (Group A) and 2757 patients with unresectable ICC who received neither radiation nor cancer-directed surgery (Group B) were included. Both groups were similar for mean age at diagnosis, gender, race, bilobar disease, portal vein thrombosis and mean largest tumor size (p>0.05). Median OS from ICC diagnosis was 20.8 months (Group A; 95% CI, 11.2-30.5) and 3.0 months (Group B; 95% CI, 2.7-3.3), p<0.001. Median OS from first Y90 was 11.5 months (Group A; 95% CI, 4.8-18.2). Interval survival rates from ICC diagnosis for Group A vs. B were: 100% vs. 77% (1 month), 100% vs. 63% (3 months), 92% vs. 30% (6 months), 67% vs. 17% (1 year), 42% vs. 6% (2 years), and 17% vs. 3% (3 years). Conclusions: Y90 radioembolization in patients with chemorefractory unresectable ICC demonstrated significantly greater median OS and favorable long-term survival rates compared to best supportive care.","Source":"Google Scholar","category":"HUMAN","training_data":"Survival Trends In Chemorefractory Unresectable Intrahepatic Cholangiocarcinoma (Icc) And The Effect Of Yttrium-90 (Y90) Radioembolization: Seer Versus Tertiary Cancer Center Background: Survival in patients with chemorefractory unresectable ICC treated with Y90 radioembolization vs. best supportive care has not been investigated in large-scale population studies. Methods: Under IRB approval, our institute’s cancer registry was queried for Y90-treated patients with chemorefractory unresectable ICC diagnosed from Jan 2002 to Nov 2011. Eighteen registries of U.S. Surveillance, Epidemiology and End Results (SEER) database were queried for patients with advanced ICC not amenable to surgery/radiation diagnosed in the same period. Baseline characteristics, median overall survival (OS) from ICC diagnosis and median OS from first Y90 were stratified by national/state cohorts. Survival analysis and 95% confidence intervals (CI) were calculated using Kaplan-Meier estimation. Results: A total of 24 patients who received Y90 therapy for chemorefractory unresectable ICC (Group A) and 2757 patients with unresectable ICC who received neither radiation nor cancer-directed surgery (Group B) were included. Both groups were similar for mean age at diagnosis, gender, race, bilobar disease, portal vein thrombosis and mean largest tumor size (p>0.05). Median OS from ICC diagnosis was 20.8 months (Group A; 95% CI, 11.2-30.5) and 3.0 months (Group B; 95% CI, 2.7-3.3), p<0.001. Median OS from first Y90 was 11.5 months (Group A; 95% CI, 4.8-18.2). Interval survival rates from ICC diagnosis for Group A vs. B were: 100% vs. 77% (1 month), 100% vs. 63% (3 months), 92% vs. 30% (6 months), 67% vs. 17% (1 year), 42% vs. 6% (2 years), and 17% vs. 3% (3 years). Conclusions: Y90 radioembolization in patients with chemorefractory unresectable ICC demonstrated significantly greater median OS and favorable long-term survival rates compared to best supportive care.\n Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"hospital admissions relation body mass index uk women prospective cohort study background adiposity associated many adverse health outcomes little direct evidence exists impact use health care services aim describe relationship body mass index bmi rates hospital admission middle aged uk women methods among 1 251 619 million women study participants 50 64 years old entry study routine data hospital admissions used estimate hospitalization rates according bmi standardization age region recruitment socioeconomic status reproductive history smoking status hormonal therapy use alcohol intake proportional hazards models used estimate adjusted relative risks hospitalization separately 25 common types admission results average 9 2 years follow 2 834 016 incident hospital admissions women bmis kg m2 22 5 22 5 25 25 30 30 35 35 standardized admission rates 95 confidence intervals cis per woman 10 year period 2 4 2 4 2 4 2 4 2 3 2 4 2 6 2 6 2 6 3 0 3 0 3 0 3 5 3 4 3 5 respectively p value heterogeneity 0 001 relative increase admission rates per 5 kg m2 increase bmi 1 12 1 12 1 13 relationship vary materially age corresponding average durations stay days per hospital visit within categories bmi 3 1 3 1 3 2 2 8 2 7 2 8 2 9 2 9 2 9 3 2 3 1 3 2 3 8 3 7 3 8 respectively p 0 001 significant increases risk admission increasing bmi observed 19 25 types hospital admission considered bmi strongly associated admissions diabetes knee replacement gallbladder disease venous thromboembolism marked associations found many common categories admission including cataracts carpal tunnel syndrome diverticulitis conclusions among women 50 84 years old england around one eight hospital admissions likely attributable overweight obesity translating around 420 000 extra hospital admissions two million extra days spent hospital annually pubmed","probabilities":0.9799733,"Title":"Hospital admissions in relation to body mass index in UK women: a prospective cohort study","Abstract":"BACKGROUND: Adiposity is associated with many adverse health outcomes but little direct evidence exists about its impact on the use of health care services. We aim to describe the relationship between body mass index (BMI) and rates of hospital admission in middle-aged UK women. METHODS: Among 1,251,619 Million Women Study participants, 50- to 64-years old at entry into the study, routine data on hospital admissions were used to estimate hospitalization rates according to BMI after standardization for age, region of recruitment, socioeconomic status, reproductive history, smoking status, hormonal therapy use and alcohol intake. Proportional hazards models were used to estimate adjusted relative risks of hospitalization separately for 25 common types of admission. RESULTS: During an average of 9.2 years follow-up, there were 2,834,016 incident hospital admissions. In women with BMIs (in kg/m2) of <22.5, 22.5 to <25, 25 to <30, 30 to <35 and 35+ standardized admission rates (and 95% confidence intervals (CIs)) per woman over a 10-year period were 2.4 (2.4 to 2.4), 2.4 (2.3 to 2.4), 2.6 (2.6 to 2.6), 3.0 (3.0 to 3.0) and 3.5 (3.4 to 3.5), respectively (P-value for heterogeneity <0.001). The relative increase in admission rates per 5 kg/m2 increase in BMI was 1.12 (1.12 to 1.13). This relationship did not vary materially by age. Corresponding average durations of stay (in days) per hospital visit within the same categories of BMI were: 3.1 (3.1 to 3.2), 2.8 (2.7 to 2.8), 2.9 (2.9 to 2.9), 3.2 (3.1 to 3.2) and 3.8 (3.7 to 3.8), respectively (P <0.001).Significant increases in the risk of admission with increasing BMI were observed for 19 of the 25 types of hospital admission considered. BMI was most strongly associated with admissions with diabetes, knee-replacement, gallbladder disease and venous thromboembolism, but marked associations were found with many other common categories of admission including cataracts, carpal tunnel syndrome and diverticulitis. CONCLUSIONS: Among women 50- to 84-years old in England, around one in eight hospital admissions are likely to be attributable to overweight or obesity, translating to around 420,000 extra hospital admissions and two million extra days spent in hospital, annually.","Source":"PubMed","category":"HUMAN","training_data":"Hospital admissions in relation to body mass index in UK women: a prospective cohort study BACKGROUND: Adiposity is associated with many adverse health outcomes but little direct evidence exists about its impact on the use of health care services. We aim to describe the relationship between body mass index (BMI) and rates of hospital admission in middle-aged UK women. METHODS: Among 1,251,619 Million Women Study participants, 50- to 64-years old at entry into the study, routine data on hospital admissions were used to estimate hospitalization rates according to BMI after standardization for age, region of recruitment, socioeconomic status, reproductive history, smoking status, hormonal therapy use and alcohol intake. Proportional hazards models were used to estimate adjusted relative risks of hospitalization separately for 25 common types of admission. RESULTS: During an average of 9.2 years follow-up, there were 2,834,016 incident hospital admissions. In women with BMIs (in kg/m2) of <22.5, 22.5 to <25, 25 to <30, 30 to <35 and 35+ standardized admission rates (and 95% confidence intervals (CIs)) per woman over a 10-year period were 2.4 (2.4 to 2.4), 2.4 (2.3 to 2.4), 2.6 (2.6 to 2.6), 3.0 (3.0 to 3.0) and 3.5 (3.4 to 3.5), respectively (P-value for heterogeneity <0.001). The relative increase in admission rates per 5 kg/m2 increase in BMI was 1.12 (1.12 to 1.13). This relationship did not vary materially by age. Corresponding average durations of stay (in days) per hospital visit within the same categories of BMI were: 3.1 (3.1 to 3.2), 2.8 (2.7 to 2.8), 2.9 (2.9 to 2.9), 3.2 (3.1 to 3.2) and 3.8 (3.7 to 3.8), respectively (P <0.001).Significant increases in the risk of admission with increasing BMI were observed for 19 of the 25 types of hospital admission considered. BMI was most strongly associated with admissions with diabetes, knee-replacement, gallbladder disease and venous thromboembolism, but marked associations were found with many other common categories of admission including cataracts, carpal tunnel syndrome and diverticulitis. CONCLUSIONS: Among women 50- to 84-years old in England, around one in eight hospital admissions are likely to be attributable to overweight or obesity, translating to around 420,000 extra hospital admissions and two million extra days spent in hospital, annually. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term outcomes self expandable metal stents predictors complications patients unresectable pancreatic biliary malignancy abstract available google scholar","probabilities":0.9799733,"Title":"Long Term Outcomes Of Self-Expandable Metal Stents And Predictors Of Complications In Patients With Unresectable Pancreatic And Biliary Malignancy","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Long Term Outcomes Of Self-Expandable Metal Stents And Predictors Of Complications In Patients With Unresectable Pancreatic And Biliary Malignancy Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"carcinoma gallbladder patterns presentation prognostic factors survival rate 11 year single centre experience background report examines patterns presentation prognostic factors survival rate patients gallbladder cancer gbc evaluated tertiary academic hospital 11 year period methods retrospective review prospectively collected database patients gbc presenting january 1998 december 2008 performed results 102 gbc patients included 69 women 33 men median age 65 5 years forty five patients presented incidental gallbladder cancer igc 57 nonincidental cancer nigc curative surgery rate 84 4 igc 29 8 nigc p 0 001 five year actuarial survival rate 63 2 patients curative intent surgery 0 patients palliative approach patients igc longer survival rate compared patients nigc median 25 8 vs 4 4 months p 0 0001 patients radical resection 42 patients difference igc nigc incidence liver involvement respectively 0 20 8 58 3 100 pt1 pt2 pt3 pt4 tumors univariate analysis showed survival rate significantly affected perineural invasion n m stage r0 resection liver involvement ca 19 9 multivariate analysis liver involvement independent factor conclusions majority patients potentially curable disease igc almost 80 patients nigc presented unresectable disease patients underwent resection curative intent actuarial 5 year survival 63 2 liver involvement independent prognostic factor patients igc pt2 advanced stage undergo second radical resection pubmed","probabilities":0.9799733,"Title":"Carcinoma of the gallbladder: patterns of presentation, prognostic factors and survival rate An 11-year single centre experience","Abstract":"BACKGROUND: This report examines the patterns of presentation, prognostic factors and survival rate of all patients with gallbladder cancer (GBC) evaluated at our tertiary academic hospital over an 11-year period. METHODS: A retrospective review of a prospectively collected database of all patients with GBC presenting between January 1998 and December 2008 was performed. RESULTS: 102 GBC-patients were included: 69 women and 33 men (median age: 65,5 years). Forty-five patients presented with incidental gallbladder cancer (IGC) and 57 with nonincidental cancer (NIGC). Curative surgery rate was 84.4% for IGC and 29.8% for NIGC (p < 0.001). Five-year actuarial survival rate was 63.2% for patients with curative intent surgery and 0% for patients with palliative approach. Patients with IGC had a longer survival rate compared to patients with NIGC (median: 25.8 vs. 4.4 months, p < 0.0001). For patients with radical resection (42 patients), there was no difference between IGC and NIGC. The incidence of liver involvement was respectively 0%, 20.8%, 58.3%, 100% for pT1, pT2, pT3 and pT4 tumors. Univariate analysis showed that survival rate was significantly affected by perineural invasion, T, N and M-stage, R0 resection, liver involvement, CA-19.9. In multivariate analysis, liver involvement was the only independent factor. CONCLUSIONS: Majority of patients with a potentially curable disease had IGC. Almost 80% of patients with NIGC presented with unresectable disease. For patients who underwent resection with curative intent, actuarial 5-year survival was 63.2%. Liver involvement was the only independent prognostic factor. All patients with IGC and a pT2 or more advanced T stage should undergo a second radical resection.","Source":"PubMed","category":"HUMAN","training_data":"Carcinoma of the gallbladder: patterns of presentation, prognostic factors and survival rate An 11-year single centre experience BACKGROUND: This report examines the patterns of presentation, prognostic factors and survival rate of all patients with gallbladder cancer (GBC) evaluated at our tertiary academic hospital over an 11-year period. METHODS: A retrospective review of a prospectively collected database of all patients with GBC presenting between January 1998 and December 2008 was performed. RESULTS: 102 GBC-patients were included: 69 women and 33 men (median age: 65,5 years). Forty-five patients presented with incidental gallbladder cancer (IGC) and 57 with nonincidental cancer (NIGC). Curative surgery rate was 84.4% for IGC and 29.8% for NIGC (p < 0.001). Five-year actuarial survival rate was 63.2% for patients with curative intent surgery and 0% for patients with palliative approach. Patients with IGC had a longer survival rate compared to patients with NIGC (median: 25.8 vs. 4.4 months, p < 0.0001). For patients with radical resection (42 patients), there was no difference between IGC and NIGC. The incidence of liver involvement was respectively 0%, 20.8%, 58.3%, 100% for pT1, pT2, pT3 and pT4 tumors. Univariate analysis showed that survival rate was significantly affected by perineural invasion, T, N and M-stage, R0 resection, liver involvement, CA-19.9. In multivariate analysis, liver involvement was the only independent factor. CONCLUSIONS: Majority of patients with a potentially curable disease had IGC. Almost 80% of patients with NIGC presented with unresectable disease. For patients who underwent resection with curative intent, actuarial 5-year survival was 63.2%. Liver involvement was the only independent prognostic factor. All patients with IGC and a pT2 or more advanced T stage should undergo a second radical resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cd86 cd206 tumor associated macrophages predict prognosis patients intrahepatic cholangiocarcinoma background main cellular ingredients tumor microenvironment tumor associated macrophages tams play vital role tumor development progression recent studies suggested tams sensitive specific prognostic factors numerous cancers primary purpose study determine prognostic significance tams intrahepatic cholangiocarcinoma icc methods immunohistochemical staining cd68 cd86 cd206 performed tissue microarrays containing 322 patients underwent surgical resection pathologically diagnosed icc prognostic value cd68 cd86 cd206 evaluated kaplan meier analysis log rank test nomogram models results demonstrated cd86 cd206 tams model independent prognostic index icc patients patients low cd86 tams high cd206 tams infiltration markedly worse prognosis increased risk post operative recurrence compared high cd86 tams low cd206 tams intratumoral infiltration furthermore subgroup analysis indicated cd86 cd206 tams model predicted prognosis icc patients powerfully single macrophage immunomarker interestingly cd86 cd206 tams model distinguish prognosis ca 199 negative icc patients generally presumed favorable outcome order perfect prognostic value cd86 cd206 tams model constructed validated postoperative nomogram predict overall survival recurrence free survival time icc patients conclusions findings indicate cd86 cd206 tams model possess potential value novel prognostic indicator icc patients stn","probabilities":0.7966102,"Title":"Cd86+/Cd206+ Tumor-Associated Macrophages Predict Prognosis Of Patients With Intrahepatic Cholangiocarcinoma","Abstract":"Background: As the main cellular ingredients of tumor microenvironment, tumor-associated macrophages (TAMs) play a vital role in tumor development and progression. Recent studies have suggested that TAMs are sensitive and specific prognostic factors in numerous cancers. The primary purpose of this study is to determine the prognostic significance of TAMs in intrahepatic cholangiocarcinoma (ICC). \n\n Methods: Immunohistochemical staining of CD68, CD86 and CD206 were performed in tissue microarrays containing 322 patients, who underwent surgical resection and were pathologically diagnosed with ICC. The prognostic value of CD68, CD86 and CD206 were evaluated by Kaplan-Meier analysis (log-rank test) and nomogram models. \n\n Results: We demonstrated that the CD86+/CD206+ TAMs model was an independent prognostic index for ICC patients. Patients with low CD86+ TAMs and high CD206+ TAMs infiltration had a markedly worse prognosis and increased risk of post-operative recurrence when compared to high CD86+ TAMs and low CD206+ TAMs intratumoral infiltration. Furthermore, subgroup analysis indicated that the CD86+/CD206+ TAMs model predicted prognosis of ICC patients more powerfully than single macrophage immunomarker. Interestingly, the CD86+/CD206+ TAMs model could further distinguish prognosis of CA-199 negative ICC patients, who were generally presumed to have a more favorable outcome. In order to further perfect the prognostic value of the CD86+/CD206+ TAMs model, we constructed and validated a postoperative nomogram to predict overall survival and recurrence-free survival time in ICC patients. \n\n Conclusions: These findings indicate that the CD86+/CD206+ TAMs model possess potential value as a novel prognostic indicator for ICC patients.","Source":"STN","category":"HUMAN","training_data":"Cd86+/Cd206+ Tumor-Associated Macrophages Predict Prognosis Of Patients With Intrahepatic Cholangiocarcinoma Background: As the main cellular ingredients of tumor microenvironment, tumor-associated macrophages (TAMs) play a vital role in tumor development and progression. Recent studies have suggested that TAMs are sensitive and specific prognostic factors in numerous cancers. The primary purpose of this study is to determine the prognostic significance of TAMs in intrahepatic cholangiocarcinoma (ICC). \n\n Methods: Immunohistochemical staining of CD68, CD86 and CD206 were performed in tissue microarrays containing 322 patients, who underwent surgical resection and were pathologically diagnosed with ICC. The prognostic value of CD68, CD86 and CD206 were evaluated by Kaplan-Meier analysis (log-rank test) and nomogram models. \n\n Results: We demonstrated that the CD86+/CD206+ TAMs model was an independent prognostic index for ICC patients. Patients with low CD86+ TAMs and high CD206+ TAMs infiltration had a markedly worse prognosis and increased risk of post-operative recurrence when compared to high CD86+ TAMs and low CD206+ TAMs intratumoral infiltration. Furthermore, subgroup analysis indicated that the CD86+/CD206+ TAMs model predicted prognosis of ICC patients more powerfully than single macrophage immunomarker. Interestingly, the CD86+/CD206+ TAMs model could further distinguish prognosis of CA-199 negative ICC patients, who were generally presumed to have a more favorable outcome. In order to further perfect the prognostic value of the CD86+/CD206+ TAMs model, we constructed and validated a postoperative nomogram to predict overall survival and recurrence-free survival time in ICC patients. \n\n Conclusions: These findings indicate that the CD86+/CD206+ TAMs model possess potential value as a novel prognostic indicator for ICC patients. STN","prediction_labels":"HUMAN"},{"cleaned":"combined resection liver pancreas malignancy background combined resection liver pancreas malignancy remains controversial procedure many need extended procedure implies extent disease isusuallynotamenabletosurgicalcontrol andtheextentoftheprocedureexposesthepatients tosubstantialoperativerisks thepurposeofthisstudywastoassessourresultswithcombined resection liver pancreas study design forty patients underwent combined liver pancreas resection 1996 2009 patient ages ranged 39 69 years mean 53 years underlying diagnoses neuroendocrine tumor 13 cholangiocarcinoma 13 gallbladder carcinoma 9 gastrointestinal stromal tumor 3 colorectal cancer 1 metastatic ocular melanoma 1 pancreatic resections included26pancreaticoduodenectomies pd and14distalpancreaticresections liverresections included 18 trisectionectomies 13 right 5 left 10 lobectomies 8 right 2 left 12 segmental resections results perioperative mortality one patient underwent pd right trisegmentectomy gallbladder cancer developed postoperative liver failure improved supportive management two patients developed bile leaks resolved conservative management one patient developed pancreatic leak hemorrhage required completion pancreatectomy meanhospitalstaywas14days range7to42days medianfollow upwas30 months range3to76months patientsundergoingresectionforneuroendocrinetumorshad better 5 year survival hepatobiliary malignancies 100 vs 37 p 0 01 conclusions combined resection liver pancreas performed safely need combined partial hepatectomy pancreatectomy remove malignancy considered contraindicationtoresectioninselectedpatients jamcollsurg2010 210 808 816 2010 american college surgeons google scholar","probabilities":0.9799733,"Title":"Combined Resection Of The Liver And Pancreas For Malignancy","Abstract":"BACKGROUND: Combined resection of both the liver and pancreas for malignancy remains a controversial procedure.To many, the need for such an extended procedure implies an extent of disease that isusuallynotamenabletosurgicalcontrol,andtheextentoftheprocedureexposesthepatients tosubstantialoperativerisks.Thepurposeofthisstudywastoassessourresultswithcombined resection of the liver and pancreas. STUDY DESIGN: Forty patients underwent combined liver and pancreas resection from 1996 to 2009. Patient ages ranged from 39 to 69 years (mean 53 years). Underlying diagnoses were neuroendocrine tumor (13), cholangiocarcinoma (13), gallbladder carcinoma (9), gastrointestinal stromal tumor (3), colorectal cancer (1), and metastatic ocular melanoma (1). Pancreatic resections included26pancreaticoduodenectomies(PD)and14distalpancreaticresections.Liverresections included 18 trisectionectomies (13 right, 5 left), 10 lobectomies (8 right, 2 left), and 12 segmental resections. RESULTS: There was no perioperative mortality. One patient who underwent PD with right trisegmentectomy for gallbladder cancer developed postoperative liver failure that improved with supportive management. Two patients developed bile leaks that resolved with conservative management. One patient developed a pancreatic leak/hemorrhage and required a completion pancreatectomy.Meanhospitalstaywas14days(range7to42days).Medianfollow-upwas30 months(range3to76months).Patientsundergoingresectionforneuroendocrinetumorshad a better 5-year survival than those with hepatobiliary malignancies (100% vs 37% p \u0001 0.01). CONCLUSIONS: Combined resection of the liver and pancreas can be performed safely.The need for combined partial hepatectomy and pancreatectomy to remove malignancy should not be considered a contraindicationtoresectioninselectedpatients.(JAmCollSurg2010;210:808–816.©2010 by the American College of Surgeons)","Source":"Google Scholar","category":"HUMAN","training_data":"Combined Resection Of The Liver And Pancreas For Malignancy BACKGROUND: Combined resection of both the liver and pancreas for malignancy remains a controversial procedure.To many, the need for such an extended procedure implies an extent of disease that isusuallynotamenabletosurgicalcontrol,andtheextentoftheprocedureexposesthepatients tosubstantialoperativerisks.Thepurposeofthisstudywastoassessourresultswithcombined resection of the liver and pancreas. STUDY DESIGN: Forty patients underwent combined liver and pancreas resection from 1996 to 2009. Patient ages ranged from 39 to 69 years (mean 53 years). Underlying diagnoses were neuroendocrine tumor (13), cholangiocarcinoma (13), gallbladder carcinoma (9), gastrointestinal stromal tumor (3), colorectal cancer (1), and metastatic ocular melanoma (1). Pancreatic resections included26pancreaticoduodenectomies(PD)and14distalpancreaticresections.Liverresections included 18 trisectionectomies (13 right, 5 left), 10 lobectomies (8 right, 2 left), and 12 segmental resections. RESULTS: There was no perioperative mortality. One patient who underwent PD with right trisegmentectomy for gallbladder cancer developed postoperative liver failure that improved with supportive management. Two patients developed bile leaks that resolved with conservative management. One patient developed a pancreatic leak/hemorrhage and required a completion pancreatectomy.Meanhospitalstaywas14days(range7to42days).Medianfollow-upwas30 months(range3to76months).Patientsundergoingresectionforneuroendocrinetumorshad a better 5-year survival than those with hepatobiliary malignancies (100% vs 37% p \u0001 0.01). CONCLUSIONS: Combined resection of the liver and pancreas can be performed safely.The need for combined partial hepatectomy and pancreatectomy to remove malignancy should not be considered a contraindicationtoresectioninselectedpatients.(JAmCollSurg2010;210:808–816.©2010 by the American College of Surgeons) Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer epidemiology pathogenesis molecular genetics recent update gallbladder cancer malignancy biliary tract infrequent developed countries common specific geographical regions developing countries late diagnosis deprived prognosis major problems treatment gallbladder carcinoma dramatic associations orphan cancer various genetic environmental factors responsible poorly defined pathogenesis understanding relationship epidemiology molecular genetics pathogenesis gallbladder cancer add new insights undetermined pathophysiology present review article provides recent update regarding epidemiology pathogenesis molecular genetics gallbladder cancer systematically reviewed published literature gallbladder cancer online search engine pubmed http www ncbi nlm nih gov pubmed various keywords used retrieval articles gallbladder cancer epidemiology molecular genetics bullion operators like cross references manually searched various online search engines http www ncbi nlm nih gov pubmed https scholar google co http www medline com home jsp articles published 1982 2015 peer reviewed journals included review pubmed","probabilities":0.9799733,"Title":"Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update","Abstract":"Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder cancer epidemiology, pathogenesis and molecular genetics: Recent update Gallbladder cancer is a malignancy of biliary tract which is infrequent in developed countries but common in some specific geographical regions of developing countries. Late diagnosis and deprived prognosis are major problems for treatment of gallbladder carcinoma. The dramatic associations of this orphan cancer with various genetic and environmental factors are responsible for its poorly defined pathogenesis. An understanding to the relationship between epidemiology, molecular genetics and pathogenesis of gallbladder cancer can add new insights to its undetermined pathophysiology. Present review article provides a recent update regarding epidemiology, pathogenesis, and molecular genetics of gallbladder cancer. We systematically reviewed published literature on gallbladder cancer from online search engine PubMed (http://www.ncbi.nlm.nih.gov/pubmed). Various keywords used for retrieval of articles were Gallbladder, cancer Epidemiology, molecular genetics and bullion operators like AND, OR, NOT. Cross references were manually searched from various online search engines (http://www.ncbi.nlm.nih.gov/pubmed,https://scholar.google.co.in/, http://www.medline.com/home.jsp). Most of the articles published from 1982 to 2015 in peer reviewed journals have been included in this review. PubMed","prediction_labels":"HUMAN"},{"cleaned":"significance metabolic tumor volume total lesion glycolysis measured using f fdg pet ct locally advanced metastatic gallbladder carcinoma purpose study aimed determine prognostic value new quantitative parameters f fluorodeoxyglucose positron emission tomography computed tomography f fdg pet ct including metabolic tumor volume mtv patients locally advanced metastatic gallbladder cancer gbc materials methods total 83 patients initially diagnosed locally advanced metastatic gbc underwent f fdg pet ct time initial diagnosis retrospectively reviewed metabolic volume based pet parameters primary tumors metastatic lesions measured including maximum average standardized uptake values suv mtv total lesion glycolysis overall survival os analysis performed using kaplan meier method pet clinical parameters cox proportional hazards regression analysis performed determine independent prognostic factors results univariate analysis pathologic differentiation p 0 001 performance status ps p 0 003 c reactive protein crp level p 0 009 pet related suv mt max highest suv among metastatic lesions p 0 040 mtv total sum mtvs primary metastatic lesions p 0 031 significant os multivariate analysis mtv total hazard ratio 2 07 95 confidence interval 1 23 3 48 p 0 006 remained significant prediction os differentiation p 0 001 ps p 0 001 crp p 0 039 conclusion locally advanced metastatic gbc volume based pet ct parameters total tumor burden malignancy mtv total found useful identification patients poor prognosis pubmed","probabilities":0.9799733,"Title":"Significance of Metabolic Tumor Volume and Total Lesion Glycolysis Measured Using ¹⁸F-FDG PET/CT in Locally Advanced and Metastatic Gallbladder Carcinoma","Abstract":"PURPOSE: This study aimed to determine the prognostic value of new quantitative parameters of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT), including metabolic tumor volume (MTV), in patients with locally advanced and metastatic gallbladder cancer (GBC). MATERIALS AND METHODS: In total, 83 patients initially diagnosed with locally advanced and metastatic GBC and who underwent ¹⁸F-FDG PET/CT at the time of initial diagnosis were retrospectively reviewed. The metabolic volume-based PET parameters of primary tumors and metastatic lesions were measured, including maximum and average standardized uptake values (SUV), MTV, and total lesion glycolysis. An overall survival (OS) analysis was performed using the Kaplan-Meier method with PET and clinical parameters. A Cox proportional hazards regression analysis was performed to determine independent prognostic factors. RESULTS: In univariate analysis, pathologic differentiation (p<0.001), performance status (PS; p=0.003), C-reactive protein (CRP) level (p=0.009), and PET-related SUV(mt max) (the highest SUV among the metastatic lesions) (p=0.040) and MTV(total) (the sum of the MTVs of both the primary and metastatic lesions) (p=0.031), were significant for OS. In multivariate analysis, MTV(total) (hazard ratio: 2.07; 95% confidence interval: 1.23-3.48; p=0.006) remained significant for the prediction of OS, as did differentiation (p=0.001), PS (p=0.001), and CRP (p=0.039). CONCLUSION: In locally advanced and metastatic GBC, volume-based PET/CT parameters of the total tumor burden of malignancy, such as MTV(total), were found to be useful for the identification of patients with poor prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Significance of Metabolic Tumor Volume and Total Lesion Glycolysis Measured Using ¹⁸F-FDG PET/CT in Locally Advanced and Metastatic Gallbladder Carcinoma PURPOSE: This study aimed to determine the prognostic value of new quantitative parameters of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (¹⁸F-FDG PET/CT), including metabolic tumor volume (MTV), in patients with locally advanced and metastatic gallbladder cancer (GBC). MATERIALS AND METHODS: In total, 83 patients initially diagnosed with locally advanced and metastatic GBC and who underwent ¹⁸F-FDG PET/CT at the time of initial diagnosis were retrospectively reviewed. The metabolic volume-based PET parameters of primary tumors and metastatic lesions were measured, including maximum and average standardized uptake values (SUV), MTV, and total lesion glycolysis. An overall survival (OS) analysis was performed using the Kaplan-Meier method with PET and clinical parameters. A Cox proportional hazards regression analysis was performed to determine independent prognostic factors. RESULTS: In univariate analysis, pathologic differentiation (p<0.001), performance status (PS; p=0.003), C-reactive protein (CRP) level (p=0.009), and PET-related SUV(mt max) (the highest SUV among the metastatic lesions) (p=0.040) and MTV(total) (the sum of the MTVs of both the primary and metastatic lesions) (p=0.031), were significant for OS. In multivariate analysis, MTV(total) (hazard ratio: 2.07; 95% confidence interval: 1.23-3.48; p=0.006) remained significant for the prediction of OS, as did differentiation (p=0.001), PS (p=0.001), and CRP (p=0.039). CONCLUSION: In locally advanced and metastatic GBC, volume-based PET/CT parameters of the total tumor burden of malignancy, such as MTV(total), were found to be useful for the identification of patients with poor prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"exogenous estrogen risk biliary tract cancer population based study cohort swedish men treated prostate cancer background assess role exogenous estrogen etiology biliary tract cancer nationwide population based cohort study sweden performed methods study included men sweden prostate cancer diagnosed 1961 2008 due treatment standards patients diagnosed 1961 1980 considered exposed estrogen diagnosed 1981 2008 regarded less exposed standardized incidence ratios sirs 95 confidence intervals cis calculated estimate risk biliary tract cancer cohort members compared corresponding swedish male population results 849 307 person years follow 203 131 prostate cancer patients 41 incident gallbladder cancers 36 cancers extra hepatic bile ducts overall apparent differences risk gallbladder cancer bile duct cancer patients diagnosed 1961 1980 patients diagnosed 1981 2008 however patients diagnosed 1961 1980 statistically non significant increased risk gallbladder cancer sir 1 34 95 ci 0 71 2 29 extra hepatic bile duct cancer sir 1 20 95 ci 0 55 2 28 5 years follow prostate cancer diagnosis association found patients diagnosed 1981 2008 sensitivity analyses excluding prostate cancer patients exposed potential confounding factors change sirs conclusions long exposure high doses exogenous estrogen might increase risk biliary tract cancer however potential excess risk bile duct cancer resulted prolonged exposure high doses exogenous estrogen seems small pubmed","probabilities":0.9799733,"Title":"Exogenous estrogen and the risk of biliary tract cancer - a population-based study in a cohort of Swedish men treated for prostate cancer","Abstract":"BACKGROUND: To assess the role of exogenous estrogen in the etiology of biliary tract cancer, a nationwide population-based cohort study in Sweden was performed. METHODS: The study included all men in Sweden with prostate cancer diagnosed in 1961-2008. Due to treatment standards, patients diagnosed in 1961-1980 were considered more exposed to estrogen, while those diagnosed in 1981-2008 were regarded less exposed. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated to estimate the risk of biliary tract cancer in cohort members compared to the corresponding Swedish male population. RESULTS: After 849 307 person-years of follow-up in 203 131 prostate cancer patients, there were 41 incident gallbladder cancers and 36 cancers of the extra-hepatic bile ducts. In overall, there were no apparent differences in the risk of gallbladder cancer or bile duct cancer between patients diagnosed in 1961-1980 and patients diagnosed in 1981-2008. However, in patients diagnosed in 1961-1980, there was a statistically non-significant increased risk of gallbladder cancer (SIR 1.34; 95% CI 0.71-2.29) and extra-hepatic bile duct cancer (SIR 1.20; 95% CI 0.55-2.28) > 5 years of follow-up after the prostate cancer diagnosis. No such association was found for patients diagnosed in 1981-2008. Sensitivity analyses excluding prostate cancer patients exposed to potential confounding factors did not change the SIRs. CONCLUSIONS: Long exposure to high doses of exogenous estrogen might increase the risk of biliary tract cancer. However, any potential excess risk of bile duct cancer resulted by prolonged exposure to high doses of exogenous estrogen seems to be small.","Source":"PubMed","category":"HUMAN","training_data":"Exogenous estrogen and the risk of biliary tract cancer - a population-based study in a cohort of Swedish men treated for prostate cancer BACKGROUND: To assess the role of exogenous estrogen in the etiology of biliary tract cancer, a nationwide population-based cohort study in Sweden was performed. METHODS: The study included all men in Sweden with prostate cancer diagnosed in 1961-2008. Due to treatment standards, patients diagnosed in 1961-1980 were considered more exposed to estrogen, while those diagnosed in 1981-2008 were regarded less exposed. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) were calculated to estimate the risk of biliary tract cancer in cohort members compared to the corresponding Swedish male population. RESULTS: After 849 307 person-years of follow-up in 203 131 prostate cancer patients, there were 41 incident gallbladder cancers and 36 cancers of the extra-hepatic bile ducts. In overall, there were no apparent differences in the risk of gallbladder cancer or bile duct cancer between patients diagnosed in 1961-1980 and patients diagnosed in 1981-2008. However, in patients diagnosed in 1961-1980, there was a statistically non-significant increased risk of gallbladder cancer (SIR 1.34; 95% CI 0.71-2.29) and extra-hepatic bile duct cancer (SIR 1.20; 95% CI 0.55-2.28) > 5 years of follow-up after the prostate cancer diagnosis. No such association was found for patients diagnosed in 1981-2008. Sensitivity analyses excluding prostate cancer patients exposed to potential confounding factors did not change the SIRs. CONCLUSIONS: Long exposure to high doses of exogenous estrogen might increase the risk of biliary tract cancer. However, any potential excess risk of bile duct cancer resulted by prolonged exposure to high doses of exogenous estrogen seems to be small. PubMed","prediction_labels":"HUMAN"},{"cleaned":"proton beam therapy unresectable intrahepatic cholangiocarcinoma background aim treatment unresectable intrahepatic cholangiocarcinoma icc established aim study evaluate outcome proton beam therapy pbt patients unresectable icc methods 2010 20 patients 11 males 9 females median age 63 years old unresectable icc two seven seven four stages ii iiia iiic iv respectively treated pbt largest dimensions tumors ranged 15 140 mm median 50 mm intrahepatic region lymph nodes received median total proton doses 72 6 gye 22 fractions 56 1 gye 17 fractions respectively four patients received concurrent chemotherapy tegafur gimeracil oteracil ts 1 pbt twelve patients treated curatively eight treated palliatively tumors present outside irradiation field results curative group nine tumors within irradiated field controlled follow 8 6 62 6 months median 20 8 months median survival rates curative palliative groups 27 5 9 6 months respectively overall 1 3 year survival rates 82 38 50 0 respectively eight patients survived 2 years distant metastasis five patients 2 years severe side effects occurred conclusions results suggest long term survival achieved using pbt patients unresectable icc without distant metastasis studies required determine optimal treatment schedule best combination pbt chemotherapy pubmed","probabilities":0.9799733,"Title":"Proton beam therapy for unresectable intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND AND AIM: Treatment for unresectable intrahepatic cholangiocarcinoma (ICC) has not been established. The aim of the study was to evaluate the outcome of proton beam therapy (PBT) for patients with unresectable ICC. METHODS: Up to 2010, 20 patients (11 males, 9 females, median age 63 years old) with unresectable ICC (two, seven, seven, and four in stages II, IIIA, IIIC, and IV, respectively) were treated with PBT. The largest dimensions of the tumors ranged from 15 to 140 mm (median: 50 mm). The intrahepatic region and lymph nodes received median total proton doses of 72.6 GyE in 22 fractions and 56.1 GyE in 17 fractions, respectively. Four patients received concurrent chemotherapy (tegafur, gimeracil, and oteracil; TS-1) during PBT. Twelve patients were treated curatively, and eight were treated palliatively because tumors were present outside the irradiation field. RESULTS: In the curative group, nine tumors within the irradiated field were controlled in follow-up of 8.6-62.6 months (median: 20.8 months). Median survival rates in the curative and palliative groups were 27.5 and 9.6 months, respectively, and overall 1- and 3-year survival rates were 82% and 38%, and 50% and 0%, respectively. Eight patients survived for > 2 years, and there was no distant metastasis in five of these patients after 2 years. No severe side-effects occurred. CONCLUSIONS: The results suggest that long-term survival can be achieved using PBT for patients with unresectable ICC without distant metastasis. Further studies are required to determine the optimal treatment schedule and best combination of PBT and chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Proton beam therapy for unresectable intrahepatic cholangiocarcinoma BACKGROUND AND AIM: Treatment for unresectable intrahepatic cholangiocarcinoma (ICC) has not been established. The aim of the study was to evaluate the outcome of proton beam therapy (PBT) for patients with unresectable ICC. METHODS: Up to 2010, 20 patients (11 males, 9 females, median age 63 years old) with unresectable ICC (two, seven, seven, and four in stages II, IIIA, IIIC, and IV, respectively) were treated with PBT. The largest dimensions of the tumors ranged from 15 to 140 mm (median: 50 mm). The intrahepatic region and lymph nodes received median total proton doses of 72.6 GyE in 22 fractions and 56.1 GyE in 17 fractions, respectively. Four patients received concurrent chemotherapy (tegafur, gimeracil, and oteracil; TS-1) during PBT. Twelve patients were treated curatively, and eight were treated palliatively because tumors were present outside the irradiation field. RESULTS: In the curative group, nine tumors within the irradiated field were controlled in follow-up of 8.6-62.6 months (median: 20.8 months). Median survival rates in the curative and palliative groups were 27.5 and 9.6 months, respectively, and overall 1- and 3-year survival rates were 82% and 38%, and 50% and 0%, respectively. Eight patients survived for > 2 years, and there was no distant metastasis in five of these patients after 2 years. No severe side-effects occurred. CONCLUSIONS: The results suggest that long-term survival can be achieved using PBT for patients with unresectable ICC without distant metastasis. Further studies are required to determine the optimal treatment schedule and best combination of PBT and chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression fam83h znf16 associated shorter survival patients gallbladder carcinoma background recently fam83h reported roles cancer progression conjunction oncogenic molecules myc b catenin moreover data public database indicates molecular relationship fam83h zinc finger proteins especially fam83h znf16 however studies fam83h znf16 gallbladder cancer limited methods study investigated expression fam83h znf16 105 gallbladder carcinomas results human gallbladder carcinomas immunohistochemical expression fam83h significantly associated znf16 expression univariate analysis nuclear cytoplasmic expression fam83h znf16 significantly associated shorter survival gallbladder carcinoma patients multivariate analysis revealed nuclear expression fam83h independent indicator poor prognosis overall survival p 0 005 relapse free survival p 0 005 gallbladder carcinoma patients moreover co expression patterns nuclear fam83h znf16 also independent indicators shorter survival gallbladder carcinoma patients overall survival p 0 001 relapse free survival p 0 001 conclusions study suggests fam83h znf16 associated progression gallbladder carcinoma expressions fam83h znf16 might novel prognostic indicators gallbladder carcinoma patients stn","probabilities":0.8333333,"Title":"Expression Of Fam83H And Znf16 Are Associated With Shorter Survival Of Patients With Gallbladder Carcinoma","Abstract":"Background: Recently, FAM83H was reported to have roles in cancer progression in conjunction with oncogenic molecules such as MYC and b-catenin. Moreover, the data from the public database indicates a molecular relationship between FAM83H and zinc finger proteins, especially between FAM83H and ZNF16. However, studies on FAM83H and ZNF16 in gallbladder cancer have been limited. \r\n\r\n Methods: This study investigated the expression of FAM83H and ZNF16 in 105 gallbladder carcinomas. \r\n\r\n Results: In human gallbladder carcinomas, immunohistochemical expression of FAM83H was significantly associated with ZNF16 expression. In univariate analysis, nuclear and cytoplasmic expression of FAM83H or ZNF16 were significantly associated with shorter survival of gallbladder carcinoma patients. Multivariate analysis revealed the nuclear expression of FAM83H as an independent indicator of poor prognosis of overall survival (p = 0.005) and relapse-free survival (p = 0.005) of gallbladder carcinoma patients. Moreover, co-expression patterns of nuclear FAM83H and ZNF16 were also independent indicators of shorter survival of gallbladder carcinoma patients (overall survival; p < 0.001, relapse-free survival; p < 0.001). \r\n\r\n Conclusions: This study suggests FAM83H and ZNF16 are associated with the progression of gallbladder carcinoma, and the expressions of FAM83H and ZNF16 might be novel prognostic indicators of gallbladder carcinoma patients.","Source":"STN","category":"HUMAN","training_data":"Expression Of Fam83H And Znf16 Are Associated With Shorter Survival Of Patients With Gallbladder Carcinoma Background: Recently, FAM83H was reported to have roles in cancer progression in conjunction with oncogenic molecules such as MYC and b-catenin. Moreover, the data from the public database indicates a molecular relationship between FAM83H and zinc finger proteins, especially between FAM83H and ZNF16. However, studies on FAM83H and ZNF16 in gallbladder cancer have been limited. \r\n\r\n Methods: This study investigated the expression of FAM83H and ZNF16 in 105 gallbladder carcinomas. \r\n\r\n Results: In human gallbladder carcinomas, immunohistochemical expression of FAM83H was significantly associated with ZNF16 expression. In univariate analysis, nuclear and cytoplasmic expression of FAM83H or ZNF16 were significantly associated with shorter survival of gallbladder carcinoma patients. Multivariate analysis revealed the nuclear expression of FAM83H as an independent indicator of poor prognosis of overall survival (p = 0.005) and relapse-free survival (p = 0.005) of gallbladder carcinoma patients. Moreover, co-expression patterns of nuclear FAM83H and ZNF16 were also independent indicators of shorter survival of gallbladder carcinoma patients (overall survival; p < 0.001, relapse-free survival; p < 0.001). \r\n\r\n Conclusions: This study suggests FAM83H and ZNF16 are associated with the progression of gallbladder carcinoma, and the expressions of FAM83H and ZNF16 might be novel prognostic indicators of gallbladder carcinoma patients. STN","prediction_labels":"HUMAN"},{"cleaned":"impact major vascular resection outcomes survival patients intrahepatic cholangiocarcinoma multi institutional analysis background major vascular involvement ivc portal vein intrahepatic cholangiocarcinoma icc traditionally considered contraindication resection sought define perioperative outcomes survival icc patients undergoing hepatectomy major vascular resection large international multi institutional database methods total 1087 icc patients underwent curative intent hepatectomy 1990 2016 identified 13 institutions multivariable logistic cox regressions used determine impact major vascular resection perioperative survival outcomes results 1087 patients underwent resection 128 11 8 also underwent major vascular resection 21 16 4 ivc resections 98 76 6 pv resections 9 7 0 combined resections despite advanced disease major vascular resection associated risk complication 0 68 95 ci 0 32 1 45 major complications 0 95 95 ci 0 49 2 00 post operative mortality also comparable groups 1 05 95 ci 0 32 3 47 addition median recurrence free 14 0 vs 14 7 months hr 0 737 95 ci 0 49 1 10 overall 33 4 vs 40 2 months hr 0 71 95 ci 0 359 1 40 survival similar among patients undergo major vascular resection p 0 05 conclusion among patients icc major vascular resection associated worse perioperative oncologic outcomes concurrent major vascular resection considered appropriately selected patients icc undergoing hepatectomy stn","probabilities":0.9799733,"Title":"Impact Of Major Vascular Resection On Outcomes And Survival In Patients With Intrahepatic Cholangiocarcinoma: A Multi-Institutional Analysis","Abstract":"Background: Major vascular involvement (IVC or portal vein) for intrahepatic cholangiocarcinoma (ICC) has traditionally been considered a contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing hepatectomy with major vascular resection in a large international multi-institutional database. \r\n\r\n Methods: A total of 1087 ICC patients who underwent curative-intent hepatectomy between 1990 and 2016 were identified from 13 institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative and survival outcomes. \r\n\r\n Results: Of 1087 patients who underwent resection, 128 (11.8%) also underwent major vascular resection (21 [16.4%] IVC resections, 98 [76.6%] PV resections, 9 [7.0%] combined resections). Despite more advanced disease, major vascular resection was not associated with the risk of any complication (OR = 0.68, 95%CI 0.32-1.45) or major complications (OR = 0.95, 95%CI 0.49-2.00). Post-operative mortality was also comparable between groups (OR = 1.05, 95%CI 0.32-3.47). In addition, median recurrence-free (14.0 vs 14.7 months, HR = 0.737, 95%CI 0.49-1.10) and overall (33.4 vs 40.2 months, HR = 0.71, 95%CI 0.359-1.40) survival were similar among patients who did and did not undergo major vascular resection (both P > 0.05). \r\n\r\n Conclusion: Among patients with ICC, major vascular resection was not associated with worse perioperative or oncologic outcomes. Concurrent major vascular resection should be considered in appropriately selected patients with ICC undergoing hepatectomy.","Source":"STN","category":"HUMAN","training_data":"Impact Of Major Vascular Resection On Outcomes And Survival In Patients With Intrahepatic Cholangiocarcinoma: A Multi-Institutional Analysis Background: Major vascular involvement (IVC or portal vein) for intrahepatic cholangiocarcinoma (ICC) has traditionally been considered a contraindication to resection. We sought to define perioperative outcomes and survival of ICC patients undergoing hepatectomy with major vascular resection in a large international multi-institutional database. \r\n\r\n Methods: A total of 1087 ICC patients who underwent curative-intent hepatectomy between 1990 and 2016 were identified from 13 institutions. Multivariable logistic and cox regressions were used to determine the impact of major vascular resection on perioperative and survival outcomes. \r\n\r\n Results: Of 1087 patients who underwent resection, 128 (11.8%) also underwent major vascular resection (21 [16.4%] IVC resections, 98 [76.6%] PV resections, 9 [7.0%] combined resections). Despite more advanced disease, major vascular resection was not associated with the risk of any complication (OR = 0.68, 95%CI 0.32-1.45) or major complications (OR = 0.95, 95%CI 0.49-2.00). Post-operative mortality was also comparable between groups (OR = 1.05, 95%CI 0.32-3.47). In addition, median recurrence-free (14.0 vs 14.7 months, HR = 0.737, 95%CI 0.49-1.10) and overall (33.4 vs 40.2 months, HR = 0.71, 95%CI 0.359-1.40) survival were similar among patients who did and did not undergo major vascular resection (both P > 0.05). \r\n\r\n Conclusion: Among patients with ICC, major vascular resection was not associated with worse perioperative or oncologic outcomes. Concurrent major vascular resection should be considered in appropriately selected patients with ICC undergoing hepatectomy. STN","prediction_labels":"HUMAN"},{"cleaned":"expression clinical significance epidermal growth factor receptor insulin like growth factor receptor 1 patients ampullary adenocarcinoma epidermal growth factor receptor egfr insulin like growth factor receptor 1 igf 1r play important roles cell proliferation antiapoptosis angiogenesis metastasis used targeted therapies patients advanced colorectal lung cancers however expression function egfr igf 1r ampullary adenocarcinoma aa examined detail examined expression egfr igf 1r 106 aa patients institution using tissue microarrays immunohistochemistry results correlated clinicopathological parameters survival overexpression egfr igf 1r detected 18 17 26 25 aas respectively patients egfr high tumors shorter overall survival mean 109 8 22 3 months patients whose tumors egfr low overall study population mean 164 2 10 6 months p 04 overexpression egfr correlated poor overall survival patients intestinal type aa p 01 pancreaticobiliary type aas p 47 multivariate analysis egfr overexpression independent prognostic factor overall survival p 02 addition found overexpression igf 1r correlated aas pancreaticobiliary histology additional correlation expression egfr igf 1r clinicopathological factors observed patient population study demonstrates egfr igf 1r appear overexpressed subset aas strong membranous expression egfr independent predictor overall survival patients aa egfr igf 1r represent potential therapeutic targets treatment patient aas pubmed","probabilities":0.962963,"Title":"Expression and clinical significance of epidermal growth factor receptor and insulin-like growth factor receptor 1 in patients with ampullary adenocarcinoma","Abstract":"Epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF-1R) play important roles in cell proliferation, antiapoptosis, angiogenesis, and metastasis and have been used for targeted therapies for patients with advanced colorectal and lung cancers. However, the expression and function of EGFR and IGF-1R in ampullary adenocarcinoma (AA) have not been examined in detail. We examined the expression of EGFR and IGF-1R in 106 AA patients at our institution using tissue microarrays and immunohistochemistry. The results were correlated with the clinicopathological parameters and survival. Overexpression of EGFR and IGF-1R was detected in 18 (17%) and 26 (25%) of AAs, respectively. Patients with EGFR-high tumors had shorter overall survival (mean, 109.8 ± 22.3 months) than those patients whose tumors were EGFR-low in overall study population (mean, 164.2 ± 10.6 months; P = .04). Overexpression of EGFR correlated with poor overall survival in patients with intestinal-type AA (P = .01) but not in those with pancreaticobiliary-type AAs (P = .47). In multivariate analysis, EGFR overexpression was an independent prognostic factor for overall survival (P = .02). In addition, we found that overexpression of IGF-1R correlated with AAs of pancreaticobiliary histology. No additional correlation between the expression of EGFR or IGF-1R and other clinicopathological factors was observed in our patient population. Our study demonstrates that EGFR and IGF-1R appear to be overexpressed in a subset of AAs and that strong membranous expression of EGFR is an independent predictor for overall survival in patients with AA. EGFR and IGF-1R represent potential therapeutic targets for treatment of patient with AAs.","Source":"PubMed","category":"HUMAN","training_data":"Expression and clinical significance of epidermal growth factor receptor and insulin-like growth factor receptor 1 in patients with ampullary adenocarcinoma Epidermal growth factor receptor (EGFR) and insulin-like growth factor receptor 1 (IGF-1R) play important roles in cell proliferation, antiapoptosis, angiogenesis, and metastasis and have been used for targeted therapies for patients with advanced colorectal and lung cancers. However, the expression and function of EGFR and IGF-1R in ampullary adenocarcinoma (AA) have not been examined in detail. We examined the expression of EGFR and IGF-1R in 106 AA patients at our institution using tissue microarrays and immunohistochemistry. The results were correlated with the clinicopathological parameters and survival. Overexpression of EGFR and IGF-1R was detected in 18 (17%) and 26 (25%) of AAs, respectively. Patients with EGFR-high tumors had shorter overall survival (mean, 109.8 ± 22.3 months) than those patients whose tumors were EGFR-low in overall study population (mean, 164.2 ± 10.6 months; P = .04). Overexpression of EGFR correlated with poor overall survival in patients with intestinal-type AA (P = .01) but not in those with pancreaticobiliary-type AAs (P = .47). In multivariate analysis, EGFR overexpression was an independent prognostic factor for overall survival (P = .02). In addition, we found that overexpression of IGF-1R correlated with AAs of pancreaticobiliary histology. No additional correlation between the expression of EGFR or IGF-1R and other clinicopathological factors was observed in our patient population. Our study demonstrates that EGFR and IGF-1R appear to be overexpressed in a subset of AAs and that strong membranous expression of EGFR is an independent predictor for overall survival in patients with AA. EGFR and IGF-1R represent potential therapeutic targets for treatment of patient with AAs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma germany epidemiologic trends impact misclassification background aims diverging trends cholangiocarcinoma cca incidence different countries warrant subtype specific characterization study aimed determine current epidemiologic trends cca germany evaluated impact misclassification perihilar cca pcca intrahepatic cca icca methods subtype specific incidence assessed based data approximately 40 million german citizens 2003 2014 mortality data entire germany assessed 1998 2015 results reclassification pcca extrahepatic cca ecca led enhancement increasing average annual percentage change aapc icca men 3 8 4 8 women 3 3 4 8 likewise stable slightly decreasing trend extrahepatic cca strengthened women aapc 0 2 0 9 men 1 0 5 pcca accounted 13 biliary tract tumours icca 46 distal cca 41 line incidence trends mortality icca germany increased women aapc 7 8 men 6 5 stable ecca women 0 6 men 2 1 conclusion incidence icca germany increasing stable ecca misclassification pcca icca present clearly declining stn","probabilities":0.9799733,"Title":"Cholangiocarcinoma In Germany: Epidemiologic Trends And Impact Of Misclassification","Abstract":"Background & aims: Diverging trends of cholangiocarcinoma (CCA) incidence in different countries warrant further subtype-specific characterization. In this study, we aimed to determine current epidemiologic trends of CCA in Germany and evaluated impact of misclassification of perihilar CCA (pCCA) as intrahepatic CCA (iCCA). \r\n\r\n Methods: Subtype-specific incidence was assessed based on data of approximately 40 million German citizens from 2003 to 2014, and mortality data of entire Germany were assessed from 1998 to 2015. \r\n\r\n Results: Reclassification of pCCA to extrahepatic CCA (eCCA) led to an enhancement of an increasing average annual percentage change (AAPC) for iCCA in men (3.8 to 4.8) and women (3.3 to 4.8). Likewise, a stable or slightly decreasing trend in extrahepatic CCA was strengthened in women (AAPC: -0.2 to -0.9) and men (1 to 0.5). pCCA accounted for 13% of biliary tract tumours (iCCA: 46%, distal CCA: 41%). In line with incidence trends, mortality of iCCA in Germany increased for women (AAPC 7.8) and men (6.5), while it was stable for eCCA (women: -0.6, men: 2.1). \r\n\r\n Conclusion: Incidence of iCCA in Germany is increasing while it is stable for eCCA. Misclassification of pCCA as iCCA is present, but clearly declining.","Source":"STN","category":"HUMAN","training_data":"Cholangiocarcinoma In Germany: Epidemiologic Trends And Impact Of Misclassification Background & aims: Diverging trends of cholangiocarcinoma (CCA) incidence in different countries warrant further subtype-specific characterization. In this study, we aimed to determine current epidemiologic trends of CCA in Germany and evaluated impact of misclassification of perihilar CCA (pCCA) as intrahepatic CCA (iCCA). \r\n\r\n Methods: Subtype-specific incidence was assessed based on data of approximately 40 million German citizens from 2003 to 2014, and mortality data of entire Germany were assessed from 1998 to 2015. \r\n\r\n Results: Reclassification of pCCA to extrahepatic CCA (eCCA) led to an enhancement of an increasing average annual percentage change (AAPC) for iCCA in men (3.8 to 4.8) and women (3.3 to 4.8). Likewise, a stable or slightly decreasing trend in extrahepatic CCA was strengthened in women (AAPC: -0.2 to -0.9) and men (1 to 0.5). pCCA accounted for 13% of biliary tract tumours (iCCA: 46%, distal CCA: 41%). In line with incidence trends, mortality of iCCA in Germany increased for women (AAPC 7.8) and men (6.5), while it was stable for eCCA (women: -0.6, men: 2.1). \r\n\r\n Conclusion: Incidence of iCCA in Germany is increasing while it is stable for eCCA. Misclassification of pCCA as iCCA is present, but clearly declining. STN","prediction_labels":"HUMAN"},{"cleaned":"capsaicin treatment attenuates cholangiocarcinoma carcinogenesis capsaicin abundant pungent molecule produced pepper plants represents important ingredient spicy foods consumed throughout world studies shown capsaicin relieve inflammation anti proliferative effects various human malignancies cholangiocarcinoma cc cancer disease rising incidence prognosis remains dismal little advance treatment aim present study explore anti tumor activity capsaicin cultured human cc cell lines capsaicin effectively impaired cell proliferation migration invasion epithelial mesenchymal transition growth softagar colonies show capsaicin treatment cc cells regulates hedgehog signaling pathway conclusion results provide basis capsaicin improve prognosis ccs vivo present new insights effectiveness mode action capsaicin google scholar","probabilities":0.9467213,"Title":"Capsaicin Treatment Attenuates Cholangiocarcinoma Carcinogenesis","Abstract":"Capsaicin, the most abundant pungent molecule produced by pepper plants, represents an important ingredient in spicy foods consumed throughout the world. Studies have shown that capsaicin can relieve inflammation and has anti-proliferative effects on various human malignancies. Cholangiocarcinoma (CC) is a cancer disease with rising incidence. The prognosis remains dismal with little advance in treatment. The aim of the present study is to explore the anti-tumor activity of capsaicin in cultured human CC cell lines. Capsaicin effectively impaired cell proliferation, migration, invasion, epithelial to mesenchymal transition and growth of softagar colonies. Further, we show that capsaicin treatment of CC cells regulates the Hedgehog signaling pathway. Conclusion: Our results provide a basis for capsaicin to improve the prognosis of CCs in vivo and present new insights into the effectiveness and mode of action of capsaicin.","Source":"Google Scholar","category":"ANIMAL","training_data":"Capsaicin Treatment Attenuates Cholangiocarcinoma Carcinogenesis Capsaicin, the most abundant pungent molecule produced by pepper plants, represents an important ingredient in spicy foods consumed throughout the world. Studies have shown that capsaicin can relieve inflammation and has anti-proliferative effects on various human malignancies. Cholangiocarcinoma (CC) is a cancer disease with rising incidence. The prognosis remains dismal with little advance in treatment. The aim of the present study is to explore the anti-tumor activity of capsaicin in cultured human CC cell lines. Capsaicin effectively impaired cell proliferation, migration, invasion, epithelial to mesenchymal transition and growth of softagar colonies. Further, we show that capsaicin treatment of CC cells regulates the Hedgehog signaling pathway. Conclusion: Our results provide a basis for capsaicin to improve the prognosis of CCs in vivo and present new insights into the effectiveness and mode of action of capsaicin. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"comparative analysis resection liver transplantation intrahepatic hilar cholangiocarcinoma 24 year experience single center objectives compare survival difference 2 surgical modalities treatment locally advanced intrahepatic hilar cholangiocarcinoma cca identify factors predict mortality design retrospective study setting university transplant center patients 132 patients diagnosis cca treated february 1 1985 june 30 2009 75 metastatic disease presentation excluded study whereas 57 patients candidates surgical therapy tumor type intrahepatic 37 patients hilar 20 patients surgical therapy included orthotopic liver transplant olt 38 patients combined radical bile duct resection partial hepatectomy rr 19 patients results tumors locally advanced 35 37 patients 95 intrahepatic tumors 16 20 patients 80 hilar tumors adjunctive therapy used 35 patients 61 5 year tumor recurrence free patient survival significantly higher olt group compared rr group 33 vs 0 p 05 olt group neoadjuvant adjuvant therapies resulted better patient survival compared therapy adjuvant therapy 47 vs 20 vs 33 respectively p 03 multivariate factors predictive worse survival outcomes included hilar cca multifocal tumors perineural invasion rr treatment modality compared olt tumor sizes 5 cm larger intrahepatic 3 cm larger hilar cca predictors poor outcome conclusion orthotopic liver transplant combination neoadjuvant adjuvant therapies superior rr adjuvant therapy locally advanced intrahepatic hilar cca pubmed","probabilities":0.9799733,"Title":"Comparative analysis of resection and liver transplantation for intrahepatic and hilar cholangiocarcinoma: a 24-year experience in a single center","Abstract":"OBJECTIVES: To compare the survival difference between 2 surgical modalities in the treatment of locally advanced intrahepatic and hilar cholangiocarcinoma (CCA) and to identify factors that predict mortality. DESIGN: Retrospective study. SETTING: University transplant center. PATIENTS: Of the 132 patients with a diagnosis of CCA treated from February 1, 1985, through June 30, 2009, 75 had metastatic disease at presentation and were excluded from the study, whereas 57 patients were candidates for surgical therapy. Tumor type was intrahepatic in 37 patients and hilar in 20 patients. Surgical therapy included orthotopic liver transplant (OLT) in 38 patients and combined radical bile duct resection with partial hepatectomy (RR) in 19 patients. RESULTS: Tumors were locally advanced in 35 of 37 patients (95%) with intrahepatic tumors and 16 of 20 patients (80%) with hilar tumors. Adjunctive therapy was used in 35 patients (61%). The 5-year tumor recurrence-free patient survival was significantly higher in the OLT group compared with the RR group (33% vs 0%; P = .05). In the OLT group, neoadjuvant and adjuvant therapies resulted in better patient survival compared with no therapy or adjuvant therapy only (47% vs 20% vs 33%, respectively; P = .03). Multivariate factors predictive of worse survival outcomes included hilar CCA, multifocal tumors, perineural invasion, and RR as the treatment modality compared with OLT. Tumor sizes--5 cm or larger for intrahepatic and 3 cm or larger for hilar CCA--were not predictors of poor outcome. CONCLUSION: Orthotopic liver transplant in combination with neoadjuvant and adjuvant therapies is superior to RR with adjuvant therapy in locally advanced intrahepatic and hilar CCA.","Source":"PubMed","category":"HUMAN","training_data":"Comparative analysis of resection and liver transplantation for intrahepatic and hilar cholangiocarcinoma: a 24-year experience in a single center OBJECTIVES: To compare the survival difference between 2 surgical modalities in the treatment of locally advanced intrahepatic and hilar cholangiocarcinoma (CCA) and to identify factors that predict mortality. DESIGN: Retrospective study. SETTING: University transplant center. PATIENTS: Of the 132 patients with a diagnosis of CCA treated from February 1, 1985, through June 30, 2009, 75 had metastatic disease at presentation and were excluded from the study, whereas 57 patients were candidates for surgical therapy. Tumor type was intrahepatic in 37 patients and hilar in 20 patients. Surgical therapy included orthotopic liver transplant (OLT) in 38 patients and combined radical bile duct resection with partial hepatectomy (RR) in 19 patients. RESULTS: Tumors were locally advanced in 35 of 37 patients (95%) with intrahepatic tumors and 16 of 20 patients (80%) with hilar tumors. Adjunctive therapy was used in 35 patients (61%). The 5-year tumor recurrence-free patient survival was significantly higher in the OLT group compared with the RR group (33% vs 0%; P = .05). In the OLT group, neoadjuvant and adjuvant therapies resulted in better patient survival compared with no therapy or adjuvant therapy only (47% vs 20% vs 33%, respectively; P = .03). Multivariate factors predictive of worse survival outcomes included hilar CCA, multifocal tumors, perineural invasion, and RR as the treatment modality compared with OLT. Tumor sizes--5 cm or larger for intrahepatic and 3 cm or larger for hilar CCA--were not predictors of poor outcome. CONCLUSION: Orthotopic liver transplant in combination with neoadjuvant and adjuvant therapies is superior to RR with adjuvant therapy in locally advanced intrahepatic and hilar CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"univariate multivariate analysis prognostic factors surgical treatment hilar cholangiocarcinoma surgery effective treatment able improve survival patients hilar cholangiocarcinoma cca however significance prognostic factors overall survival still debated evaluated early long term outcomes patients resected hilar cholangiocarcinoma 3 year period determine role prognostic factors effect overall survival medical records patients hilar cca underwent resection january 2001 december 2004 retrospectively reviewed univariate multivariate analysis performed identify prognostic factors associated survival thirty two 45 patients underwent surgical resection curative intent morbidity 24 4 per cent perioperative mortality 0 per cent overall median survival 22 3 months well differentiated tumor grading r0 resection independently associated better survival multivariate analysis aggressive surgery including biliary resection combined major hepatectomy safe procedure low morbidity mortality tertiary referral hepatobiliary center main aim aggressive surgical approach obtain microscopic margin negative resection associated better prognosis another important prognostic factor tumor grading independently associated survival pubmed","probabilities":0.9799733,"Title":"Univariate and multivariate analysis of prognostic factors in the surgical treatment of hilar cholangiocarcinoma","Abstract":"Surgery is the only effective treatment able to improve survival of patients with hilar cholangiocarcinoma (CCA). However, the significance of prognostic factors on overall survival is still debated. We evaluated early and long-term outcomes of patients resected for hilar cholangiocarcinoma over a 3-year period to determine the role of prognostic factors and their effect on overall survival. Medical records of patients with hilar CCA who underwent resection between January 2001 and December 2004 were retrospectively reviewed. Univariate and multivariate analysis was performed to identify prognostic factors associated with survival. Thirty-two of 45 patients underwent surgical resection with curative intent. Morbidity was 24.4 per cent; perioperative mortality was 0 per cent. Overall median survival was 22.3 months. Well-differentiated tumor grading and R0 resection were independently associated with better survival at multivariate analysis. Aggressive surgery, including biliary resection combined with major hepatectomy, is a safe procedure with low morbidity and mortality in a tertiary referral hepatobiliary center. The main aim of an aggressive surgical approach is to obtain a microscopic margin-negative resection, which is associated with better prognosis. Another important prognostic factor is tumor grading, which is independently associated with survival.","Source":"PubMed","category":"HUMAN","training_data":"Univariate and multivariate analysis of prognostic factors in the surgical treatment of hilar cholangiocarcinoma Surgery is the only effective treatment able to improve survival of patients with hilar cholangiocarcinoma (CCA). However, the significance of prognostic factors on overall survival is still debated. We evaluated early and long-term outcomes of patients resected for hilar cholangiocarcinoma over a 3-year period to determine the role of prognostic factors and their effect on overall survival. Medical records of patients with hilar CCA who underwent resection between January 2001 and December 2004 were retrospectively reviewed. Univariate and multivariate analysis was performed to identify prognostic factors associated with survival. Thirty-two of 45 patients underwent surgical resection with curative intent. Morbidity was 24.4 per cent; perioperative mortality was 0 per cent. Overall median survival was 22.3 months. Well-differentiated tumor grading and R0 resection were independently associated with better survival at multivariate analysis. Aggressive surgery, including biliary resection combined with major hepatectomy, is a safe procedure with low morbidity and mortality in a tertiary referral hepatobiliary center. The main aim of an aggressive surgical approach is to obtain a microscopic margin-negative resection, which is associated with better prognosis. Another important prognostic factor is tumor grading, which is independently associated with survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"time recurrence surgical resection survival recurrence among patients perihilar distal cholangiocarcinomas background differences perihilar cholangiocarcinoma phcc distal cholangiocarcinoma dcc regarding recurrence factors affect recurrence surgery unclear study aims investigate differences recurrence patterns patients phcc dcc surgical resection curative intent also investigates risk factors associated recurrence survival thereafter patients methods postoperative courses 366 patients extrahepatic cholangiocarcinomas ehccs including 236 phcc 130 dcc underwent surgical resections investigated retrospectively results follow tumors recurred 143 60 6 patients phcc 72 55 4 patients dcc overall survival os surgery recurrence free survival rfs os recurrence similar patients phcc dcc cumulative probability recurrence declined 3 years surgery patients phcc dcc multivariable analysis determined among patients phcc dcc regional lymph node metastasis significant risk factor associated rfs ten patients phcc eight patients dcc two fewer sites recurrence single organ underwent resections multivariable analysis determined recurrent tumor resection independent prognostic factor associated os recurrence patients phcc dcc conclusions postoperative survival differ patients phcc dcc frequent surveillances recurrence needed 3 years surgical resection ehccs selected patients surgery recurrent ehccs might associated improved outcomes stn","probabilities":0.9799733,"Title":"Time To Recurrence After Surgical Resection And Survival After Recurrence Among Patients With Perihilar And Distal Cholangiocarcinomas","Abstract":"Background: The differences between perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC) regarding recurrence and the factors that affect recurrence after surgery are unclear. This study aims to investigate the differences in recurrence patterns between patients with PHCC and those with DCC after surgical resection with curative intent. It also investigates the risk factors associated with recurrence and survival thereafter. \r\n\r\n Patients and methods: The postoperative courses of 366 patients with extrahepatic cholangiocarcinomas (EHCCs), including 236 with PHCC and 130 with DCC, who underwent surgical resections were investigated retrospectively. \r\n\r\n Results: During follow-up, tumors recurred in 143 (60.6%) patients with PHCC and in 72 (55.4%) patients with DCC. Overall survival (OS) after surgery, recurrence-free survival (RFS), and OS after recurrence were similar for the patients with PHCC and those with DCC. The cumulative probability of recurrence declined 3 years after surgery in the patients with PHCC and those with DCC. A multivariable analysis determined that, among the patients with PHCC and those with DCC, regional lymph node metastasis was a significant risk factor associated with RFS. Ten patients with PHCC and eight patients with DCC with two or fewer sites of recurrence in a single organ underwent resections. A multivariable analysis determined that recurrent tumor resection was an independent prognostic factor associated with OS after recurrence in the patients with PHCC and those with DCC. \r\n\r\n Conclusions: Postoperative survival did not differ between the patients with PHCC and those with DCC. Frequent surveillances for recurrence are needed for 3 years after surgical resection of EHCCs. In selected patients, surgery for recurrent EHCCs might be associated with improved outcomes.","Source":"STN","category":"HUMAN","training_data":"Time To Recurrence After Surgical Resection And Survival After Recurrence Among Patients With Perihilar And Distal Cholangiocarcinomas Background: The differences between perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC) regarding recurrence and the factors that affect recurrence after surgery are unclear. This study aims to investigate the differences in recurrence patterns between patients with PHCC and those with DCC after surgical resection with curative intent. It also investigates the risk factors associated with recurrence and survival thereafter. \r\n\r\n Patients and methods: The postoperative courses of 366 patients with extrahepatic cholangiocarcinomas (EHCCs), including 236 with PHCC and 130 with DCC, who underwent surgical resections were investigated retrospectively. \r\n\r\n Results: During follow-up, tumors recurred in 143 (60.6%) patients with PHCC and in 72 (55.4%) patients with DCC. Overall survival (OS) after surgery, recurrence-free survival (RFS), and OS after recurrence were similar for the patients with PHCC and those with DCC. The cumulative probability of recurrence declined 3 years after surgery in the patients with PHCC and those with DCC. A multivariable analysis determined that, among the patients with PHCC and those with DCC, regional lymph node metastasis was a significant risk factor associated with RFS. Ten patients with PHCC and eight patients with DCC with two or fewer sites of recurrence in a single organ underwent resections. A multivariable analysis determined that recurrent tumor resection was an independent prognostic factor associated with OS after recurrence in the patients with PHCC and those with DCC. \r\n\r\n Conclusions: Postoperative survival did not differ between the patients with PHCC and those with DCC. Frequent surveillances for recurrence are needed for 3 years after surgical resection of EHCCs. In selected patients, surgery for recurrent EHCCs might be associated with improved outcomes. STN","prediction_labels":"HUMAN"},{"cleaned":"cyclin dependent kinase pathway involving cdk1 potential therapeutic target cholangiocarcinoma cholangiocarcinoma aggressive malignancy high mortality effective therapeutic agents cancer limited cyclin dependent kinase cdk pathways therapeutic targets various types cancers however involvement cholangiocarcinoma remains unclear present study examined biological significance cdk pathways cholangiocarcinoma immunohistochemical analysis cholangiocarcinoma tissue sections revealed upregulated expression phosphorylated cyclin dependent kinase 1 p cdk1 p cdk2 cyclin b1 cyclin e1 carcinoma cells nuclear expression p cdk1 cyclin b1 positively correlated presence lymph node metastasis clinical stage p cdk1 expression also associated poor patient survival treatment human cholangiocarcinoma cell lines ccks 1 tfk 1 hucct 1 multi cdk inhibitor roscovitine decreased p cdk1 expression inhibited cell proliferation arrested cell cycle g1 g2 m phase significantly inhibited carcinoma cell invasion vivo studies using murine xenograft model revealed intraperitoneal injection roscovitine significantly inhibited cholangiocarcinoma cell growth roscovitine induced apoptosis cholangiocarcinoma cells vitro vivo results demonstrated potential cdk pathway involving cdk1 therapeutic target cholangiocarcinoma furthermore immunohistochemical expression p cdk1 may useful prognostic marker cholangiocarcinoma google scholar","probabilities":0.9467213,"Title":"The Cyclin-Dependent Kinase Pathway Involving Cdk1 Is A Potential Therapeutic Target For Cholangiocarcinoma","Abstract":"Cholangiocarcinoma is an aggressive malignancy with high mortality, and effective therapeutic agents for this cancer are limited. Cyclin‑dependent kinase (CDK) pathways are therapeutic targets for various types of cancers; however, their involvement in cholangiocarcinoma remains unclear. The present study examined the biological significance of CDK pathways in cholangiocarcinoma. An immunohistochemical analysis of cholangiocarcinoma tissue sections revealed the upregulated expression of phosphorylated cyclin‑dependent kinase 1 (p‑CDK1), p‑CDK2, cyclin B1, and cyclin E1 in carcinoma cells. The nuclear expression of p‑CDK1 and cyclin B1 was positively correlated with the presence of lymph node metastasis and the clinical stage, and p‑CDK1 expression was also associated with poor patient survival. The treatment of human cholangiocarcinoma cell lines (CCKS‑1, TFK‑1 and HUCCT‑1) with the multi‑CDK inhibitor roscovitine decreased p‑CDK1 expression, inhibited cell proliferation, arrested the cell cycle at the G1 or G2/M phase, and significantly inhibited carcinoma cell invasion. In vivo studies using a murine xenograft model revealed that an intraperitoneal injection of roscovitine significantly inhibited cholangiocarcinoma cell growth. Roscovitine induced apoptosis in cholangiocarcinoma cells in vitro and in vivo. These results demonstrated the potential of the CDK pathway involving CDK1 as a therapeutic target for cholangiocarcinoma. Furthermore, the immunohistochemical expression of p‑CDK1 may be a useful prognostic marker of cholangiocarcinoma.","Source":"Google Scholar","category":"ANIMAL","training_data":"The Cyclin-Dependent Kinase Pathway Involving Cdk1 Is A Potential Therapeutic Target For Cholangiocarcinoma Cholangiocarcinoma is an aggressive malignancy with high mortality, and effective therapeutic agents for this cancer are limited. Cyclin‑dependent kinase (CDK) pathways are therapeutic targets for various types of cancers; however, their involvement in cholangiocarcinoma remains unclear. The present study examined the biological significance of CDK pathways in cholangiocarcinoma. An immunohistochemical analysis of cholangiocarcinoma tissue sections revealed the upregulated expression of phosphorylated cyclin‑dependent kinase 1 (p‑CDK1), p‑CDK2, cyclin B1, and cyclin E1 in carcinoma cells. The nuclear expression of p‑CDK1 and cyclin B1 was positively correlated with the presence of lymph node metastasis and the clinical stage, and p‑CDK1 expression was also associated with poor patient survival. The treatment of human cholangiocarcinoma cell lines (CCKS‑1, TFK‑1 and HUCCT‑1) with the multi‑CDK inhibitor roscovitine decreased p‑CDK1 expression, inhibited cell proliferation, arrested the cell cycle at the G1 or G2/M phase, and significantly inhibited carcinoma cell invasion. In vivo studies using a murine xenograft model revealed that an intraperitoneal injection of roscovitine significantly inhibited cholangiocarcinoma cell growth. Roscovitine induced apoptosis in cholangiocarcinoma cells in vitro and in vivo. These results demonstrated the potential of the CDK pathway involving CDK1 as a therapeutic target for cholangiocarcinoma. Furthermore, the immunohistochemical expression of p‑CDK1 may be a useful prognostic marker of cholangiocarcinoma. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"high single session success rate endoscopic bilateral stent stent placement modified large cell niti stents malignant hilar biliary obstruction background endoscopic bilateral self expandable metallic stent sems placement stent stent method malignant hilar biliary obstruction technically challenging technical difficulties initial placement reinterventions stent occlusion disadvantages inherent stent stent method previously reported feasibility niti large cell d type biliary stents lcd multicenter prospective consecutive study evaluated efficacy bilateral sems placement using modified lcd large uniform cells slimmer delivery system high radial force patients methods july 2010 june 2011 26 consecutive patients unresectable malignant hilar biliary obstruction underwent endoscopic bilateral placement modified lcd stent stent method three tertiary hospitals ten patients gallbladder cancer eight cholangiocarcinoma four lymph node metastasis two intrahepatic cholangiocarcinoma two liver metastasis results single session final technical success rate 96 100 respectively functional success rate 89 stent occlusion occurred 11 patients 42 sludge n 7 tumor ingrowth n 4 endoscopic bilateral reintervention technically easy successful six patients stent clearance balloon sweeping five plastic stent placement according kaplan meier analysis median survival stent patency 220 days 157 days respectively conclusions modified lcd achieved high technical success rate initial stent stent placement bilateral reinterventions patients malignant hilar biliary obstruction pubmed","probabilities":0.962963,"Title":"High single-session success rate of endoscopic bilateral stent-in-stent placement with modified large cell Niti-S stents for malignant hilar biliary obstruction","Abstract":"BACKGROUND: Endoscopic bilateral self-expandable metallic stent (SEMS) placement in a stent-in-stent method for malignant hilar biliary obstruction is technically challenging. Technical difficulties in the initial placement and reinterventions for stent occlusion are disadvantages inherent to this stent-in-stent method. We previously reported the feasibility of Niti-S large cell D-type biliary stents (LCD). This multicenter prospective consecutive study evaluated the efficacy of bilateral SEMS placement using modified LCD with large and uniform cells, a slimmer delivery system and high radial force. PATIENTS AND METHODS: From July 2010 to June 2011, 26 consecutive patients with unresectable malignant hilar biliary obstruction underwent endoscopic bilateral placement of modified LCD in a stent-in-stent method at three tertiary hospitals. Ten patients had gallbladder cancer, eight had cholangiocarcinoma, four had lymph node metastasis, two had intrahepatic cholangiocarcinoma, and two had liver metastasis. RESULTS: Single-session and final technical success rate was 96% and 100%, respectively. Functional success rate was 89%. Stent occlusion occurred in 11 patients (42%) because of sludge (n = 7) or tumor ingrowth (n = 4). Endoscopic bilateral reintervention was technically easy and successful: six patients had stent clearance by balloon sweeping and five had plastic stent placement. According to Kaplan-Meier analysis, median survival and stent patency were 220 days and 157 days, respectively. CONCLUSIONS: Modified LCD achieved a high technical success rate both in the initial stent-in-stent placement and in bilateral reinterventions in patients with malignant hilar biliary obstruction.","Source":"PubMed","category":"HUMAN","training_data":"High single-session success rate of endoscopic bilateral stent-in-stent placement with modified large cell Niti-S stents for malignant hilar biliary obstruction BACKGROUND: Endoscopic bilateral self-expandable metallic stent (SEMS) placement in a stent-in-stent method for malignant hilar biliary obstruction is technically challenging. Technical difficulties in the initial placement and reinterventions for stent occlusion are disadvantages inherent to this stent-in-stent method. We previously reported the feasibility of Niti-S large cell D-type biliary stents (LCD). This multicenter prospective consecutive study evaluated the efficacy of bilateral SEMS placement using modified LCD with large and uniform cells, a slimmer delivery system and high radial force. PATIENTS AND METHODS: From July 2010 to June 2011, 26 consecutive patients with unresectable malignant hilar biliary obstruction underwent endoscopic bilateral placement of modified LCD in a stent-in-stent method at three tertiary hospitals. Ten patients had gallbladder cancer, eight had cholangiocarcinoma, four had lymph node metastasis, two had intrahepatic cholangiocarcinoma, and two had liver metastasis. RESULTS: Single-session and final technical success rate was 96% and 100%, respectively. Functional success rate was 89%. Stent occlusion occurred in 11 patients (42%) because of sludge (n = 7) or tumor ingrowth (n = 4). Endoscopic bilateral reintervention was technically easy and successful: six patients had stent clearance by balloon sweeping and five had plastic stent placement. According to Kaplan-Meier analysis, median survival and stent patency were 220 days and 157 days, respectively. CONCLUSIONS: Modified LCD achieved a high technical success rate both in the initial stent-in-stent placement and in bilateral reinterventions in patients with malignant hilar biliary obstruction. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatitis c virus infection cholangiocarcinoma insight epidemiologic evidences hypothetical mechanisms oncogenesis hepatitis c virus hcv infection global public health problem main cause liver cirrhosis hepatocellular carcinoma human oncogenic virus also associated development non hodgkin lymphoma cholangiocarcinoma cca association hcv infection cca examined number epidemiologic studies however vivo vitro results demonstrating oncogenic mechanisms hcv cca development progression insufficient review epidemiologic association hcv cca recent publications studies hcv infection cholangiocytes cca cell lines well studies viral infection performed liver samples obtained patients addition also discuss preliminary results vitro assays hcv protein expression cca cell lines finally discuss hypothetical role hcv infection cca development induction epithelial mesenchymal transition regulation hedgehog signaling consequently biliary tree inflammation liver fibrosis studies required demonstrate hypotheses therefore elucidate mechanisms hcv risk factor cca pubmed","probabilities":0.875,"Title":"Hepatitis C Virus Infection and Cholangiocarcinoma: An Insight into Epidemiologic Evidences and Hypothetical Mechanisms of Oncogenesis","Abstract":"Hepatitis C virus (HCV) infection is a global public health problem because it is a main cause of liver cirrhosis and hepatocellular carcinoma. This human oncogenic virus is also associated with the development of non-Hodgkin lymphoma and cholangiocarcinoma (CCA). The association between HCV infection and CCA has been examined in a number of epidemiologic studies. However, in vivo and in vitro results demonstrating the oncogenic mechanisms of HCV in CCA development and progression are insufficient. Here, we review the epidemiologic association of HCV and CCA and recent publications of studies of HCV infection of cholangiocytes and CCA cell lines as well as studies of viral infection performed with liver samples obtained from patients. In addition, we also discuss the preliminary results of in vitro assays of HCV protein expression in CCA cell lines. Finally, we discuss the hypothetical role of HCV infection in CCA development by induction of epithelial-mesenchymal transition and up-regulation of hedgehog signaling, and consequently biliary tree inflammation and liver fibrosis. Further studies are required to demonstrate these hypotheses and therefore to elucidate the mechanisms of HCV as a risk factor for CCA.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis C Virus Infection and Cholangiocarcinoma: An Insight into Epidemiologic Evidences and Hypothetical Mechanisms of Oncogenesis Hepatitis C virus (HCV) infection is a global public health problem because it is a main cause of liver cirrhosis and hepatocellular carcinoma. This human oncogenic virus is also associated with the development of non-Hodgkin lymphoma and cholangiocarcinoma (CCA). The association between HCV infection and CCA has been examined in a number of epidemiologic studies. However, in vivo and in vitro results demonstrating the oncogenic mechanisms of HCV in CCA development and progression are insufficient. Here, we review the epidemiologic association of HCV and CCA and recent publications of studies of HCV infection of cholangiocytes and CCA cell lines as well as studies of viral infection performed with liver samples obtained from patients. In addition, we also discuss the preliminary results of in vitro assays of HCV protein expression in CCA cell lines. Finally, we discuss the hypothetical role of HCV infection in CCA development by induction of epithelial-mesenchymal transition and up-regulation of hedgehog signaling, and consequently biliary tree inflammation and liver fibrosis. Further studies are required to demonstrate these hypotheses and therefore to elucidate the mechanisms of HCV as a risk factor for CCA. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"incidence significance gata3 positivity pancreatic ductal adenocarcinoma cholangiocarcinoma gata3 transcription factor involved development differentiation lymphocytes breast hair follicles protein useful immunohistochemical ihc marker supporting diagnoses breast urothelial carcinoma especially helpful metastatic neoplasms help delineate site origin gata3 also reportedly positive percentage pancreatic ductal adenocarcinomas pdacs cholangiocarcinomas ccs study closely evaluated relationship respect clininopathologic features patient outcome using tissue microarrays analyzed 240 pdacs 60 ccs gata3 ihc compared expression various clinical pathologic parameters overall gata3 positivity seen 16 pdacs 5 ccs gata3 positivity pdac cases common male patients p 0 013 gata3 positive pdacs trended toward worse survival multivariate analysis p 0 074 3 gata3 positive ccs poorly differentiated p 0 069 low case number precluded multivariate survival analysis ccs gata3 positivity occur carcinomas pancreatobiliary system considered ihc workup neoplasms unclear origin positivity seems minimal relevance patient outcome stn","probabilities":0.7966102,"Title":"Incidence And Significance Of Gata3 Positivity In Pancreatic Ductal Adenocarcinoma And Cholangiocarcinoma","Abstract":"GATA3 is a transcription factor involved in the development and differentiation of lymphocytes, breast, and hair follicles. The protein is a useful immunohistochemical (IHC) marker for supporting diagnoses of breast or urothelial carcinoma. This can be especially helpful in metastatic neoplasms to help delineate site of origin. GATA3 is also reportedly positive in a percentage of pancreatic ductal adenocarcinomas (PDACs) and cholangiocarcinomas (CCs), but no study has closely evaluated this relationship with respect to clininopathologic features or patient outcome. Using tissue microarrays, we analyzed 240 PDACs and 60 CCs with GATA3 IHC and compared expression to various clinical and pathologic parameters. Overall, GATA3 positivity was seen in 16% of PDACs and 5% of CCs. GATA3 positivity in PDAC cases was more common in male patients (P=0.013). GATA3-positive PDACs trended toward worse survival on multivariate analysis (P=0.074). The only 3 GATA3-positive CCs were poorly differentiated (P=0.069); low case number precluded multivariate survival analysis for CCs. GATA3 positivity can occur in carcinomas of the pancreatobiliary system, which should be considered during IHC workup of neoplasms of unclear origin. This positivity seems to have minimal relevance to patient outcome.","Source":"STN","category":"ANIMAL","training_data":"Incidence And Significance Of Gata3 Positivity In Pancreatic Ductal Adenocarcinoma And Cholangiocarcinoma GATA3 is a transcription factor involved in the development and differentiation of lymphocytes, breast, and hair follicles. The protein is a useful immunohistochemical (IHC) marker for supporting diagnoses of breast or urothelial carcinoma. This can be especially helpful in metastatic neoplasms to help delineate site of origin. GATA3 is also reportedly positive in a percentage of pancreatic ductal adenocarcinomas (PDACs) and cholangiocarcinomas (CCs), but no study has closely evaluated this relationship with respect to clininopathologic features or patient outcome. Using tissue microarrays, we analyzed 240 PDACs and 60 CCs with GATA3 IHC and compared expression to various clinical and pathologic parameters. Overall, GATA3 positivity was seen in 16% of PDACs and 5% of CCs. GATA3 positivity in PDAC cases was more common in male patients (P=0.013). GATA3-positive PDACs trended toward worse survival on multivariate analysis (P=0.074). The only 3 GATA3-positive CCs were poorly differentiated (P=0.069); low case number precluded multivariate survival analysis for CCs. GATA3 positivity can occur in carcinomas of the pancreatobiliary system, which should be considered during IHC workup of neoplasms of unclear origin. This positivity seems to have minimal relevance to patient outcome. STN","prediction_labels":"HUMAN"},{"cleaned":"gallbladder carcinoma 6 years experience tertiary referral center introduction gallbladder carcinoma uncommon neoplasm often fatal high geographical variability relation incidence aims methods authors propose evaluate clinical pathological aspects neoplasm relation cholelithiasis well prognosis retrospective analysis patients diagnosis gallbladder cancer 2008 2013 referral tertiary center results included 44 patients 68 women median age 70 years median time follow 6 months mortality rate 71 n 31 majority patients 61 history cholelithiasis 46 diagnosed cholecystectomy 35 context acute cholecystitis common symptoms reported admission abdominal pain 59 jaundice 41 nausea vomiting 34 majority patients slight cholestasis laboratorial analysis neoplasms involved gallbladder body panvesicular 77 cases non specific adenocarcinoma common diagnosis 86 median size 33mm diagnosis 84 advanced stage iii iv surgery curative intent performed 59 patients palliative approaches frequently used percutaneous drainage 39 chemorradiotherapy 27 endoscopic drainage performed 6 patients 14 mortality rate 3 6 12 24 months 23 39 55 66 respectively presence cholestasis p 0 036 renal dysfunction p 0 012 diagnosis correlated independently early mortality conclusion gallbladder carcinoma prevalent women advanced age many cases prior cholelithiasis advanced stage diagnosis adenocarcinoma common histological type despite high rate surgical approaches curative intent 66 survive beyond 2 years diagnosis google scholar","probabilities":0.9799733,"Title":"Gallbladder Carcinoma: The 6 Years Experience Of A Tertiary Referral Center","Abstract":"Introduction: The gallbladder carcinoma is an uncommon neoplasm but often fatal, with a high geographical variability in relation to its incidence. Aims & Methods: The authors propose to evaluate the clinical and pathological aspects of this neoplasm and its relation with cholelithiasis, as well as its prognosis. Retrospective analysis of patients with diagnosis of gallbladder cancer between 2008-2013, in a referral tertiary center. Results: We included 44 patients (68% women), with a median age of 70 years. The median time of follow-up was 6 months, with a mortality rate of 71% (n= 31). The majority of patients (61%) had history of cholelithiasis and 46% were diagnosed after cholecystectomy (35% of these in the context of acute cholecystitis). The most common symptoms reported at admission were abdominal pain (59%), jaundice (41%), and nausea/vomiting (34%). The majority of the patients had slight cholestasis in laboratorial analysis. The neoplasms involved the gallbladder body or were panvesicular in 77% of cases. A non-specific adenocarcinoma was the most common diagnosis (86%), with a median size of 33mm. At diagnosis, 84% were in an advanced stage (III/IV). A surgery of curative intent was performed in 59% of patients. The palliative approaches more frequently used were percutaneous drainage (39%) and chemorradiotherapy (27%). An endoscopic drainage was performed only in 6 patients (14%). The mortality rate at 3, 6, 12 and 24 months was 23%, 39%, 55% and 66%, respectively. The presence of cholestasis (p=0.036) and renal dysfunction (p=0.012) at diagnosis correlated independently with early mortality. Conclusion: The gallbladder carcinoma was more prevalent in women with advanced age, in many cases with prior cholelithiasis and in an advanced stage at diagnosis. Adenocarcinoma was the most common histological type. Despite the high rate of surgical approaches for curative intent, 66% did not survive beyond 2 years after the diagnosis.","Source":"Google Scholar","category":"HUMAN","training_data":"Gallbladder Carcinoma: The 6 Years Experience Of A Tertiary Referral Center Introduction: The gallbladder carcinoma is an uncommon neoplasm but often fatal, with a high geographical variability in relation to its incidence. Aims & Methods: The authors propose to evaluate the clinical and pathological aspects of this neoplasm and its relation with cholelithiasis, as well as its prognosis. Retrospective analysis of patients with diagnosis of gallbladder cancer between 2008-2013, in a referral tertiary center. Results: We included 44 patients (68% women), with a median age of 70 years. The median time of follow-up was 6 months, with a mortality rate of 71% (n= 31). The majority of patients (61%) had history of cholelithiasis and 46% were diagnosed after cholecystectomy (35% of these in the context of acute cholecystitis). The most common symptoms reported at admission were abdominal pain (59%), jaundice (41%), and nausea/vomiting (34%). The majority of the patients had slight cholestasis in laboratorial analysis. The neoplasms involved the gallbladder body or were panvesicular in 77% of cases. A non-specific adenocarcinoma was the most common diagnosis (86%), with a median size of 33mm. At diagnosis, 84% were in an advanced stage (III/IV). A surgery of curative intent was performed in 59% of patients. The palliative approaches more frequently used were percutaneous drainage (39%) and chemorradiotherapy (27%). An endoscopic drainage was performed only in 6 patients (14%). The mortality rate at 3, 6, 12 and 24 months was 23%, 39%, 55% and 66%, respectively. The presence of cholestasis (p=0.036) and renal dysfunction (p=0.012) at diagnosis correlated independently with early mortality. Conclusion: The gallbladder carcinoma was more prevalent in women with advanced age, in many cases with prior cholelithiasis and in an advanced stage at diagnosis. Adenocarcinoma was the most common histological type. Despite the high rate of surgical approaches for curative intent, 66% did not survive beyond 2 years after the diagnosis. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"epidemiology gallbladder cancer gallbladder cancer common biliary tract cancer highest incidence rates occur chile also highest mortality rates lethal gastrointestinal cancer predilection among adult women older subjects sexes also among populations throughout central eastern europe certain racial groups native american indians unfortunately prospects poor preventing form cancer pubmed","probabilities":0.9799733,"Title":"Epidemiology of gallbladder cancer","Abstract":"Gallbladder cancer is the most common biliary tract cancer. The highest incidence rates occur in Chile, which also has the highest mortality rates. This lethal gastrointestinal cancer has a predilection among adult women and older subjects of both sexes, and also among populations throughout central and Eastern Europe and certain racial groups, such as Native American Indians. Unfortunately, prospects are poor for preventing this form of cancer.","Source":"PubMed","category":"HUMAN","training_data":"Epidemiology of gallbladder cancer Gallbladder cancer is the most common biliary tract cancer. The highest incidence rates occur in Chile, which also has the highest mortality rates. This lethal gastrointestinal cancer has a predilection among adult women and older subjects of both sexes, and also among populations throughout central and Eastern Europe and certain racial groups, such as Native American Indians. Unfortunately, prospects are poor for preventing this form of cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"biliary tract cancer incidence united states demographic temporal variations anatomic site evaluated incidence patterns biliary tract cancers gallbladder extrahepatic bile duct ampulla vater otherwise specified provide potential insight etiology cancers data obtained population based surveillance epidemiology end results program rates cases diagnosed 1992 2009 calculated racial ethnic gender age groups temporal trends 1974 2009 annual percentage changes apc 1992 2009 estimated age adjusted rates site higher among american indian alaska natives hispanics white asian pacific islanders asian pi lower among whites blacks gallbladder cancer common among women ethnic groups female male incidence rate ratio irr ranged 1 24 2 86 bile duct ampulla vater cancers common among men female male irr 0 57 0 82 gallbladder cancer rates declined among racial ethnic gender groups except blacks apc 0 4 3 9 contrast extrahepatic bile duct cancer rates rose significantly female racial ethnic groups apcs among whites 0 8 among females 1 3 among males significant rates ampulla vater cancer decreased among asian pi females apc 2 7 remained stable groups addition confirming biliary tract cancer incidence patterns differ gender site gallbladder cancer incidence rates declining study provides novel evidence extrahepatic bile duct cancer rates rising observations may help guide future etiologic studies stn","probabilities":0.9799733,"Title":"Biliary Tract Cancer Incidence In The United States-Demographic And Temporal Variations By Anatomic Site","Abstract":"We evaluated incidence patterns of biliary tract cancers (gallbladder, extrahepatic bile duct, ampulla of Vater and not otherwise specified) to provide potential insight into the etiology of these cancers. Data were obtained from the population-based Surveillance, Epidemiology and End Results program. Rates for cases diagnosed during 1992-2009 were calculated by racial/ethnic, gender and age groups. Temporal trends during 1974-2009 and annual percentage changes (APC) during 1992-2009 were estimated. Age-adjusted rates by site were higher among American Indian/Alaska Natives, Hispanics (white) and Asian/Pacific Islanders (Asian/PI) and lower among whites and blacks. Gallbladder cancer was more common among women in all ethnic groups (female-to-male incidence rate ratio [IRR] ranged from 1.24 to 2.86), but bile duct and ampulla of Vater cancers were more common among men (female-to-male IRR 0.57 to 0.82). Gallbladder cancer rates declined among all racial/ethnic and gender groups except blacks (APC -0.4% to -3.9%). In contrast, extrahepatic bile duct cancer rates rose significantly in most female racial/ethnic groups; the APCs among whites were 0.8 among females and 1.3 among males, both significant. Rates for ampulla of Vater cancer decreased among Asian/PI females (APC -2.7%) but remained stable for the other groups. In addition to confirming that biliary tract cancer incidence patterns differ by gender and site and that the gallbladder cancer incidence rates have been declining, our study provides novel evidence that extrahepatic bile duct cancer rates are rising. These observations may help guide future etiologic studies.","Source":"STN","category":"HUMAN","training_data":"Biliary Tract Cancer Incidence In The United States-Demographic And Temporal Variations By Anatomic Site We evaluated incidence patterns of biliary tract cancers (gallbladder, extrahepatic bile duct, ampulla of Vater and not otherwise specified) to provide potential insight into the etiology of these cancers. Data were obtained from the population-based Surveillance, Epidemiology and End Results program. Rates for cases diagnosed during 1992-2009 were calculated by racial/ethnic, gender and age groups. Temporal trends during 1974-2009 and annual percentage changes (APC) during 1992-2009 were estimated. Age-adjusted rates by site were higher among American Indian/Alaska Natives, Hispanics (white) and Asian/Pacific Islanders (Asian/PI) and lower among whites and blacks. Gallbladder cancer was more common among women in all ethnic groups (female-to-male incidence rate ratio [IRR] ranged from 1.24 to 2.86), but bile duct and ampulla of Vater cancers were more common among men (female-to-male IRR 0.57 to 0.82). Gallbladder cancer rates declined among all racial/ethnic and gender groups except blacks (APC -0.4% to -3.9%). In contrast, extrahepatic bile duct cancer rates rose significantly in most female racial/ethnic groups; the APCs among whites were 0.8 among females and 1.3 among males, both significant. Rates for ampulla of Vater cancer decreased among Asian/PI females (APC -2.7%) but remained stable for the other groups. In addition to confirming that biliary tract cancer incidence patterns differ by gender and site and that the gallbladder cancer incidence rates have been declining, our study provides novel evidence that extrahepatic bile duct cancer rates are rising. These observations may help guide future etiologic studies. STN","prediction_labels":"HUMAN"},{"cleaned":"neither neoadjuvant adjuvant therapy increases survival biliary tract cancer resection wide negative margins background investigated role neoadjuvant adjuvant therapies survival resectable biliary tract cancer hypothesized neoadjuvant adjuvant therapy improve survival probability patients methods retrospective review prospective database patients resected gallbladder cancer gbc cholangiocarcinoma cc one hundred fifty seven patients underwent resection primary gbc n 63 cc n 94 fisher exact test student test log rank test cox proportional hazard model determined significant differences results 5 year overall survival rate resection gbc cc 50 6 30 4 respectively patients 17 8 received neoadjuvant chemotherapy 48 7 received adjuvant chemotherapy 15 8 received adjuvant chemoradiotherapy patients negative margins least 1 cm 5 year survival rate 52 4 p 0 01 adjuvant therapy significantly prolong survival neoadjuvant therapy delayed surgical resection average 6 8 months p 0 0001 immediate resection increased median survival 42 3 53 5 months p 0 01 conclusions early surgical resection biliary tract malignancies 1 cm tumor free margins provides best probability long term survival currently available neoadjuvant adjuvant therapy improve survival pubmed","probabilities":0.9799733,"Title":"Neither neoadjuvant nor adjuvant therapy increases survival after biliary tract cancer resection with wide negative margins","Abstract":"BACKGROUND: We investigated the role of neoadjuvant/adjuvant therapies on survival for resectable biliary tract cancer. We hypothesized that neoadjuvant and adjuvant therapy should improve the survival probability in these patients. METHODS: This was a retrospective review of a prospective database of patients resected for gallbladder cancer (GBC) and cholangiocarcinoma (CC). One hundred fifty-seven patients underwent resection for primary GBC (n = 63) and CC (n = 94). Fisher's exact test, Student's t test, the log-rank test, and a Cox proportional hazard model determined significant differences. RESULTS: The 5-year overall survival rate after resection of GBC and CC was 50.6 % and 30.4 %, respectively. Of the patients, 17.8 % received neoadjuvant chemotherapy, 48.7 % received adjuvant chemotherapy, while 15.8 % received adjuvant chemoradiotherapy. Patients with negative margins of at least 1 cm had a 5-year survival rate of 52.4 % (p < 0.01). Adjuvant therapy did not significantly prolong survival. Neoadjuvant therapy delayed surgical resection on average for 6.8 months (p < 0.0001). Immediate resection increased median survival from 42.3 to 53.5 months (p = 0.01). CONCLUSIONS: Early surgical resection of biliary tract malignancies with 1 cm tumor-free margins provides the best probability for long-term survival. Currently available neoadjuvant or adjuvant therapy does not improve survival.","Source":"PubMed","category":"HUMAN","training_data":"Neither neoadjuvant nor adjuvant therapy increases survival after biliary tract cancer resection with wide negative margins BACKGROUND: We investigated the role of neoadjuvant/adjuvant therapies on survival for resectable biliary tract cancer. We hypothesized that neoadjuvant and adjuvant therapy should improve the survival probability in these patients. METHODS: This was a retrospective review of a prospective database of patients resected for gallbladder cancer (GBC) and cholangiocarcinoma (CC). One hundred fifty-seven patients underwent resection for primary GBC (n = 63) and CC (n = 94). Fisher's exact test, Student's t test, the log-rank test, and a Cox proportional hazard model determined significant differences. RESULTS: The 5-year overall survival rate after resection of GBC and CC was 50.6 % and 30.4 %, respectively. Of the patients, 17.8 % received neoadjuvant chemotherapy, 48.7 % received adjuvant chemotherapy, while 15.8 % received adjuvant chemoradiotherapy. Patients with negative margins of at least 1 cm had a 5-year survival rate of 52.4 % (p < 0.01). Adjuvant therapy did not significantly prolong survival. Neoadjuvant therapy delayed surgical resection on average for 6.8 months (p < 0.0001). Immediate resection increased median survival from 42.3 to 53.5 months (p = 0.01). CONCLUSIONS: Early surgical resection of biliary tract malignancies with 1 cm tumor-free margins provides the best probability for long-term survival. Currently available neoadjuvant or adjuvant therapy does not improve survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cold atmospheric plasma induces tumor cell death preclinical vivo vitro models human cholangiocarcinoma last decade cold atmospheric plasma cap emerged innovative therapeutic option cancer treatment recently set potentially safe atmospheric pressure plasma jet device displays antitumoral properties preclinical model cholangiocarcinoma cca rare aggressive cancer emerging biliary tree efficient treatments present study aimed deciphering molecular mechanisms underlying antitumor effects cap towards cca vivo vitro context vivo using subcutaneous xenografts immunocompromised mice cap treatment cca induced dna lesions tumor cell apoptosis evaluated 8 oxoguanine cleaved caspase 3 immunohistochemistry respectively analysis tumor microenvironment showed changes markers related macrophage polarization vitro incubation cca cells cap treated culture media e plasma activated media pam led dose response decrease cell survival molecular level cap treatment induced double strand dna breaks followed increased phosphorylation activation cell cycle master regulators chk1 p53 leading cell cycle arrest cell death apoptosis conclusion cap novel therapeutic option consider cca future stn","probabilities":0.9467213,"Title":"Cold-Atmospheric Plasma Induces Tumor Cell Death In Preclinical In Vivo And In Vitro Models Of Human Cholangiocarcinoma","Abstract":"Through the last decade, cold atmospheric plasma (CAP) has emerged as an innovative therapeutic option for cancer treatment. Recently, we have set up a potentially safe atmospheric pressure plasma jet device that displays antitumoral properties in a preclinical model of cholangiocarcinoma (CCA), a rare and very aggressive cancer emerging from the biliary tree with few efficient treatments. In the present study, we aimed at deciphering the molecular mechanisms underlying the antitumor effects of CAP towards CCA in both an in vivo and in vitro context. In vivo, using subcutaneous xenografts into immunocompromised mice, CAP treatment of CCA induced DNA lesions and tumor cell apoptosis, as evaluated by 8-oxoguanine and cleaved caspase-3 immunohistochemistry, respectively. The analysis of the tumor microenvironment showed changes in markers related to macrophage polarization. In vitro, the incubation of CCA cells with CAP-treated culture media (i.e., plasma-activated media, PAM) led to a dose response decrease in cell survival. At molecular level, CAP treatment induced double-strand DNA breaks, followed by an increased phosphorylation and activation of the cell cycle master regulators CHK1 and p53, leading to cell cycle arrest and cell death by apoptosis. In conclusion, CAP is a novel therapeutic option to consider for CCA in the future.","Source":"STN","category":"ANIMAL","training_data":"Cold-Atmospheric Plasma Induces Tumor Cell Death In Preclinical In Vivo And In Vitro Models Of Human Cholangiocarcinoma Through the last decade, cold atmospheric plasma (CAP) has emerged as an innovative therapeutic option for cancer treatment. Recently, we have set up a potentially safe atmospheric pressure plasma jet device that displays antitumoral properties in a preclinical model of cholangiocarcinoma (CCA), a rare and very aggressive cancer emerging from the biliary tree with few efficient treatments. In the present study, we aimed at deciphering the molecular mechanisms underlying the antitumor effects of CAP towards CCA in both an in vivo and in vitro context. In vivo, using subcutaneous xenografts into immunocompromised mice, CAP treatment of CCA induced DNA lesions and tumor cell apoptosis, as evaluated by 8-oxoguanine and cleaved caspase-3 immunohistochemistry, respectively. The analysis of the tumor microenvironment showed changes in markers related to macrophage polarization. In vitro, the incubation of CCA cells with CAP-treated culture media (i.e., plasma-activated media, PAM) led to a dose response decrease in cell survival. At molecular level, CAP treatment induced double-strand DNA breaks, followed by an increased phosphorylation and activation of the cell cycle master regulators CHK1 and p53, leading to cell cycle arrest and cell death by apoptosis. In conclusion, CAP is a novel therapeutic option to consider for CCA in the future. STN","prediction_labels":"ANIMAL"},{"cleaned":"stathmin1 regulates p27 expression proliferation drug resistance resulting poor clinical prognosis cholangiocarcinoma patients extrahepatic cholangiocarcinoma ehcc poor prognosis postoperative survival depends cancer progression therapeutic resistance mechanism ehcc progression needs clarified identify ways improve disease prognosis stathmin1 stmn1 major cytosolic phosphoprotein regulates microtubule dynamics associated malignant phenotypes chemoresistance various cancers recently stmn1 reported interact p27 inhibitor cyclin dependent kinase complexes eighty ehcc cases studied using immunohistochemistry clinical pathology determine correlation stmn1 p27 expression rna interference analyze function stmn1 ehcc cell line also used cytoplasmic stmn1 expression correlated venous invasion p 0 0021 nuclear p27 underexpression p 0 0011 patients high stmn1 expression group associated shorter recurrence free survival overall survival low expression group vitro protein binding assay revealed cytoplasmic stmn1 bound p27 cytoplasm nucleus ehcc cells moreover p27 accumulated ehcc cells stmn1 suppression stmn1 knockdown inhibited proliferation increased sensitivity ehcc cells paclitaxel stmn1 contributes poor prognosis cancer progression ehcc patients understanding regulation p27 stmn1 provide new insights overcoming therapeutic resistance ehcc stn","probabilities":0.9467213,"Title":"Stathmin1 Regulates P27 Expression Proliferation And Drug Resistance Resulting In Poor Clinical Prognosis In Cholangiocarcinoma","Abstract":"Patients with extrahepatic cholangiocarcinoma (EHCC) have a poor prognosis; postoperative survival depends on cancer progression and therapeutic resistance. The mechanism of EHCC progression needs to be clarified to identify ways to improve disease prognosis. Stathmin1 (STMN1) is a major cytosolic phosphoprotein that regulates microtubule dynamics and is associated with malignant phenotypes and chemoresistance in various cancers. Recently, STMN1 was reported to interact with p27, an inhibitor of cyclin-dependent kinase complexes. Eighty EHCC cases were studied using immunohistochemistry and clinical pathology to determine the correlation between STMN1 and p27 expression; RNA interference to analyze the function of STMN1 in an EHCC cell line was also used. Cytoplasmic STMN1 expression correlated with venous invasion (P = 0.0021) and nuclear p27 underexpression (P = 0.0011). Patients in the high-STMN1-expression group were associated with shorter recurrence-free survival and overall survival than those in the low-expression group. An in vitro protein-binding assay revealed that cytoplasmic STMN1 bound to p27 in the cytoplasm, but not in the nucleus of EHCC cells. Moreover, p27 accumulated in EHCC cells after STMN1 suppression. STMN1 knockdown inhibited proliferation and increased the sensitivity of EHCC cells to paclitaxel. STMN1 contributes to a poor prognosis and cancer progression in EHCC patients. Understanding the regulation of p27 by STMN1 could provide new insights for overcoming therapeutic resistance in EHCC.","Source":"STN","category":"ANIMAL","training_data":"Stathmin1 Regulates P27 Expression Proliferation And Drug Resistance Resulting In Poor Clinical Prognosis In Cholangiocarcinoma Patients with extrahepatic cholangiocarcinoma (EHCC) have a poor prognosis; postoperative survival depends on cancer progression and therapeutic resistance. The mechanism of EHCC progression needs to be clarified to identify ways to improve disease prognosis. Stathmin1 (STMN1) is a major cytosolic phosphoprotein that regulates microtubule dynamics and is associated with malignant phenotypes and chemoresistance in various cancers. Recently, STMN1 was reported to interact with p27, an inhibitor of cyclin-dependent kinase complexes. Eighty EHCC cases were studied using immunohistochemistry and clinical pathology to determine the correlation between STMN1 and p27 expression; RNA interference to analyze the function of STMN1 in an EHCC cell line was also used. Cytoplasmic STMN1 expression correlated with venous invasion (P = 0.0021) and nuclear p27 underexpression (P = 0.0011). Patients in the high-STMN1-expression group were associated with shorter recurrence-free survival and overall survival than those in the low-expression group. An in vitro protein-binding assay revealed that cytoplasmic STMN1 bound to p27 in the cytoplasm, but not in the nucleus of EHCC cells. Moreover, p27 accumulated in EHCC cells after STMN1 suppression. STMN1 knockdown inhibited proliferation and increased the sensitivity of EHCC cells to paclitaxel. STMN1 contributes to a poor prognosis and cancer progression in EHCC patients. Understanding the regulation of p27 by STMN1 could provide new insights for overcoming therapeutic resistance in EHCC. STN","prediction_labels":"ANIMAL"},{"cleaned":"diagnosis cholangiocarcinoma primary sclerosing cholangitis primary sclerosing cholangitis psc chronic inflammatory disease hepatobiliary system characterized chronic inflammation progressive fibrosis stricture formation destruction extrahepatic intrahepatic bile ducts areas covered increased incidence cholangiocarcinoma cca psc well documented explained continuous inflammation biliary tree leading enhanced dysplasia carcinoma sequence although psc patients may progress liver cirrhosis cca commonly occurs ages 30 45 years cirrhosis yet developed therefore cca patients psc occurs earlier patients without psc expert commentary despite improvement diagnostic methods devices dilemma diagnosing cca patients psc solved yet needs investigation pubmed","probabilities":0.9799733,"Title":"Diagnosis of cholangiocarcinoma in primary sclerosing cholangitis","Abstract":"Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the hepatobiliary system characterized by chronic inflammation, progressive fibrosis, stricture formation and destruction of extrahepatic and intrahepatic bile ducts. Areas covered: The increased incidence of cholangiocarcinoma (CCA) in PSC has been well documented and can be explained by the continuous inflammation in the biliary tree leading to an enhanced dysplasia-carcinoma sequence. Although PSC patients may progress to liver cirrhosis; CCA most commonly occurs between the ages of 30 and 45 years when cirrhosis has not yet developed. Therefore, CCA in patients with PSC occurs earlier than in patients without PSC. Expert commentary: Despite improvement in diagnostic methods and devices, the dilemma of diagnosing CCA in patients with PSC has not been solved yet and needs further investigation.","Source":"PubMed","category":"HUMAN","training_data":"Diagnosis of cholangiocarcinoma in primary sclerosing cholangitis Primary sclerosing cholangitis (PSC) is a chronic inflammatory disease of the hepatobiliary system characterized by chronic inflammation, progressive fibrosis, stricture formation and destruction of extrahepatic and intrahepatic bile ducts. Areas covered: The increased incidence of cholangiocarcinoma (CCA) in PSC has been well documented and can be explained by the continuous inflammation in the biliary tree leading to an enhanced dysplasia-carcinoma sequence. Although PSC patients may progress to liver cirrhosis; CCA most commonly occurs between the ages of 30 and 45 years when cirrhosis has not yet developed. Therefore, CCA in patients with PSC occurs earlier than in patients without PSC. Expert commentary: Despite improvement in diagnostic methods and devices, the dilemma of diagnosing CCA in patients with PSC has not been solved yet and needs further investigation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"associations autoimmune conditions hepatobiliary cancer risk among elderly us adults growing evidence suggests people autoimmune conditions may increased risk hepatobiliary tumors present study evaluated associations autoimmune conditions hepatobiliary cancers among adults aged 66 united states used surveillance epidemiology end results seer medicare data 1992 2013 conduct population based case control study cases n 32 443 primary hepatobiliary cancer controls n 200 000 randomly selected cancer free adults frequency matched cases sex age year selection using multivariable logistic regression calculated odds ratios ors 95 confidence intervals cis associations 39 autoimmune conditions identified via medicare claims also conducted separate analyses diagnoses obtained via inpatient versus outpatient claims sixteen conditions associated least one hepatobiliary cancer strongest risk estimates primary biliary cholangitis hepatocellular carcinoma 31 33 95 ci 23 63 41 56 primary sclerosing cholangitis intrahepatic cholangiocarcinoma 7 53 5 73 10 57 extrahepatic cholangiocarcinoma 5 59 4 03 7 75 gallbladder cancer 2 06 1 27 3 33 ampulla vater cancer 6 29 4 29 9 22 associations hepatobiliary related conditions group observed across nearly cancer sites ors ranging 4 53 95 ci 3 30 6 21 extrahepatic cholangiocarcinoma 7 18 5 94 8 67 hepatocellular carcinoma restricting autoimmune conditions diagnosed via inpatient claims 6 conditions remained associated least one hepatobiliary cancer several risk estimates increased outpatient restricted analysis 12 conditions remained associated multiple autoimmune conditions associated hepatobiliary cancer risk us medicare population supporting shared immuno inflammatory etiology cancers pubmed","probabilities":0.9799733,"Title":"Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults","Abstract":"Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992-2013) to conduct a population-based, case-control study. Cases (n = 32,443) had primary hepatobiliary cancer. Controls (n = 200,000) were randomly selected, cancer-free adults frequency-matched to cases by sex, age and year of selection. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with 39 autoimmune conditions identified via Medicare claims. We also conducted separate analyses for diagnoses obtained via inpatient versus outpatient claims. Sixteen conditions were associated with at least one hepatobiliary cancer. The strongest risk estimates were for primary biliary cholangitis with hepatocellular carcinoma (OR: 31.33 [95% CI: 23.63-41.56]) and primary sclerosing cholangitis with intrahepatic cholangiocarcinoma (7.53 [5.73-10.57]), extrahepatic cholangiocarcinoma (5.59 [4.03-7.75]), gallbladder cancer (2.06 [1.27-3.33]) and ampulla of Vater cancer (6.29 [4.29-9.22]). Associations with hepatobiliary-related conditions as a group were observed across nearly all cancer sites (ORs ranging from 4.53 [95% CI: 3.30-6.21] for extrahepatic cholangiocarcinoma to 7.18 [5.94-8.67] for hepatocellular carcinoma). Restricting to autoimmune conditions diagnosed via inpatient claims, 6 conditions remained associated with at least one hepatobiliary cancer, and several risk estimates increased. In the outpatient restricted analysis, 12 conditions remained associated. Multiple autoimmune conditions are associated with hepatobiliary cancer risk in the US Medicare population, supporting a shared immuno-inflammatory etiology to these cancers.","Source":"PubMed","category":"HUMAN","training_data":"Associations between autoimmune conditions and hepatobiliary cancer risk among elderly US adults Growing evidence suggests that people with autoimmune conditions may be at increased risk of hepatobiliary tumors. In the present study, we evaluated associations between autoimmune conditions and hepatobiliary cancers among adults aged ≥66 in the United States. We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data (1992-2013) to conduct a population-based, case-control study. Cases (n = 32,443) had primary hepatobiliary cancer. Controls (n = 200,000) were randomly selected, cancer-free adults frequency-matched to cases by sex, age and year of selection. Using multivariable logistic regression, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with 39 autoimmune conditions identified via Medicare claims. We also conducted separate analyses for diagnoses obtained via inpatient versus outpatient claims. Sixteen conditions were associated with at least one hepatobiliary cancer. The strongest risk estimates were for primary biliary cholangitis with hepatocellular carcinoma (OR: 31.33 [95% CI: 23.63-41.56]) and primary sclerosing cholangitis with intrahepatic cholangiocarcinoma (7.53 [5.73-10.57]), extrahepatic cholangiocarcinoma (5.59 [4.03-7.75]), gallbladder cancer (2.06 [1.27-3.33]) and ampulla of Vater cancer (6.29 [4.29-9.22]). Associations with hepatobiliary-related conditions as a group were observed across nearly all cancer sites (ORs ranging from 4.53 [95% CI: 3.30-6.21] for extrahepatic cholangiocarcinoma to 7.18 [5.94-8.67] for hepatocellular carcinoma). Restricting to autoimmune conditions diagnosed via inpatient claims, 6 conditions remained associated with at least one hepatobiliary cancer, and several risk estimates increased. In the outpatient restricted analysis, 12 conditions remained associated. Multiple autoimmune conditions are associated with hepatobiliary cancer risk in the US Medicare population, supporting a shared immuno-inflammatory etiology to these cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"infections helicobacter spp biliary system associated biliary tract cancer meta analysis objective helicobacter spp successfully isolated biliary system hypothetical question raised role organisms development biliary tract cancer meta analysis carried explore association helicobacter spp infection biliary tract cancer methods systematic literature search carried identify eligible articles meta analysis used odds ratio random effect model 95 confidence intervals odds ratios calculated heterogeneity quantitatively assessed using test significance set p value 0 01 measured using statistic results ten studies published 2002 2011 finally included meta analysis helicobacter pylori helicobacter bilis helicobacter hepaticus helicobacter ganmani studied heterogeneity 0 p 0 685 significantly higher pooled infection rate helicobacter spp observed biliary tract cancer group compared normal group p 0 0001 benign biliary disease group respectively p 0 0001 studies east asia south asia showed higher prevalence helicobacter spp malignant group evidence supporting higher presence helicobacter spp cancer group obtained using pcr immunohistochemical analysis specimens bile biliary tissues conclusion meta analysis suggests trend higher presence helicobacter spp patients biliary tract cancers compared normal controls benign biliary diseases pubmed","probabilities":0.88235295,"Title":"Infections of Helicobacter spp in the biliary system are associated with biliary tract cancer: a meta-analysis","Abstract":"OBJECTIVE: As Helicobacter spp. have been successfully isolated from the biliary system, a hypothetical question was raised about the role of these organisms in the development of biliary tract cancer. This meta-analysis has been carried out to explore the association between Helicobacter spp. infection and biliary tract cancer. METHODS: A systematic literature search was carried out to identify all eligible articles. Meta-analysis used odds ratio and a random-effect model, and 95% confidence intervals for odds ratios were calculated. Heterogeneity was quantitatively assessed using the χ-test, with significance set at a P-value of 0.01, and was measured using the I-statistic. RESULTS: Ten studies published between 2002 and 2011 were finally included for meta-analysis. Helicobacter pylori, Helicobacter bilis, Helicobacter hepaticus, and Helicobacter ganmani were studied. With heterogeneity (I=0%, P=0.685), a significantly higher pooled infection rate of Helicobacter spp. was observed in the biliary tract cancer group compared with the normal group (P=0.0001) and the benign biliary disease group, respectively (P=0.0001). Studies from East Asia and South Asia showed a higher prevalence of Helicobacter spp. in the malignant group. Evidence supporting the higher presence of Helicobacter spp. in the cancer group was obtained using PCR and immunohistochemical analysis of specimens from bile and biliary tissues. CONCLUSION: Our meta-analysis suggests a trend of a higher presence of Helicobacter spp. in patients with biliary tract cancers compared with normal controls or those with benign biliary diseases.","Source":"PubMed","category":"HUMAN","training_data":"Infections of Helicobacter spp in the biliary system are associated with biliary tract cancer: a meta-analysis OBJECTIVE: As Helicobacter spp. have been successfully isolated from the biliary system, a hypothetical question was raised about the role of these organisms in the development of biliary tract cancer. This meta-analysis has been carried out to explore the association between Helicobacter spp. infection and biliary tract cancer. METHODS: A systematic literature search was carried out to identify all eligible articles. Meta-analysis used odds ratio and a random-effect model, and 95% confidence intervals for odds ratios were calculated. Heterogeneity was quantitatively assessed using the χ-test, with significance set at a P-value of 0.01, and was measured using the I-statistic. RESULTS: Ten studies published between 2002 and 2011 were finally included for meta-analysis. Helicobacter pylori, Helicobacter bilis, Helicobacter hepaticus, and Helicobacter ganmani were studied. With heterogeneity (I=0%, P=0.685), a significantly higher pooled infection rate of Helicobacter spp. was observed in the biliary tract cancer group compared with the normal group (P=0.0001) and the benign biliary disease group, respectively (P=0.0001). Studies from East Asia and South Asia showed a higher prevalence of Helicobacter spp. in the malignant group. Evidence supporting the higher presence of Helicobacter spp. in the cancer group was obtained using PCR and immunohistochemical analysis of specimens from bile and biliary tissues. CONCLUSION: Our meta-analysis suggests a trend of a higher presence of Helicobacter spp. in patients with biliary tract cancers compared with normal controls or those with benign biliary diseases. PubMed","prediction_labels":"HUMAN"},{"cleaned":"smoking alcohol consumption risks biliary tract cancer intrahepatic bile duct cancer background smoking alcohol established risk factors several types cancer effects biliary cancers comprising biliary tract cancer btc intrahepatic bile duct cancer ihbdc inconclusive methods population based prospective cohort study japan investigated association smoking alcohol consumption risks btc subtypes ihbdc incidence men women furthermore association smoking stratified drinking status investigated hazard ratios hrs 95 confidence intervals cis calculated using cox proportional hazard model results total 48 367 men 54 776 women aged 40 69 years enrolled 1990 1994 followed 846 417 person years men 1 021 330 person years women 2012 246 btc 80 ihbdc male cases 227 btc 60 ihbdc female cases identified men smoking significantly associated increased risk ihbdc hr 2 25 95 ci 1 19 4 25 current smokers 30 pack years compared non smokers risk enhanced among regular drinkers compared non occasional drinkers hr 3 48 95 ci 1 41 8 61 non significant increase ihbdc risk associated alcohol observed neither smoking alcohol consumption associated btc risk women association smoking alcohol consumption ihbdc btc unclear current smokers regular drinkers conclusion findings suggest smoking increases ihbdc risk men especially among regular drinkers pubmed","probabilities":0.9799733,"Title":"Smoking, Alcohol Consumption, and Risks for Biliary Tract Cancer and Intrahepatic Bile Duct Cancer","Abstract":"BACKGROUND: Smoking and alcohol are established risk factors for several types of cancer, but the effects on biliary cancers, comprising biliary tract cancer (BTC) and intrahepatic bile duct cancer (IHBDC), have been inconclusive. METHODS: In this population-based prospective cohort study in Japan, we investigated the association of smoking and alcohol consumption with the risks of BTC and its subtypes and IHBDC incidence in men and women. Furthermore, the association of smoking stratified by drinking status was investigated. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model. RESULTS: A total of 48,367 men and 54,776 women aged 40-69 years were enrolled from 1990 through 1994 and followed up for 846,417 person-years in men and 1,021,330 person-years in women until 2012, during which 246 BTC and 80 IHBDC male cases and 227 BTC and 60 IHBDC female cases were identified. In men, smoking was significantly associated with an increased risk of IHBDC (HR 2.25; 95% CI, 1.19-4.25 for current smokers with ≥30 pack-years compared with non-smokers), and the risk was enhanced among regular drinkers compared with non/occasional-drinkers (HR 3.48; 95% CI, 1.41-8.61). A non-significant increase of IHBDC risk associated with alcohol was observed. Neither smoking nor alcohol consumption was associated with BTC risk. In women, the association of smoking and alcohol consumption with IHBDC and BTC was unclear because current smokers and regular drinkers were very few. CONCLUSION: Our findings suggest that smoking increases IHBDC risk in men, especially among regular drinkers.","Source":"PubMed","category":"HUMAN","training_data":"Smoking, Alcohol Consumption, and Risks for Biliary Tract Cancer and Intrahepatic Bile Duct Cancer BACKGROUND: Smoking and alcohol are established risk factors for several types of cancer, but the effects on biliary cancers, comprising biliary tract cancer (BTC) and intrahepatic bile duct cancer (IHBDC), have been inconclusive. METHODS: In this population-based prospective cohort study in Japan, we investigated the association of smoking and alcohol consumption with the risks of BTC and its subtypes and IHBDC incidence in men and women. Furthermore, the association of smoking stratified by drinking status was investigated. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model. RESULTS: A total of 48,367 men and 54,776 women aged 40-69 years were enrolled from 1990 through 1994 and followed up for 846,417 person-years in men and 1,021,330 person-years in women until 2012, during which 246 BTC and 80 IHBDC male cases and 227 BTC and 60 IHBDC female cases were identified. In men, smoking was significantly associated with an increased risk of IHBDC (HR 2.25; 95% CI, 1.19-4.25 for current smokers with ≥30 pack-years compared with non-smokers), and the risk was enhanced among regular drinkers compared with non/occasional-drinkers (HR 3.48; 95% CI, 1.41-8.61). A non-significant increase of IHBDC risk associated with alcohol was observed. Neither smoking nor alcohol consumption was associated with BTC risk. In women, the association of smoking and alcohol consumption with IHBDC and BTC was unclear because current smokers and regular drinkers were very few. CONCLUSION: Our findings suggest that smoking increases IHBDC risk in men, especially among regular drinkers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"s100a6 promotes proliferation intrahepatic cholangiocarcinoma cells via activation p38 mapk pathway aim explored expression s100a6 role intrahepatic cholangiocarcinoma icc methods expression s100a6 icc samples detected immunohistochemistry vitro experiments silenced overexpressed s100a6 investigate role cell functions results expression s100a6 markedly increased icc tissues cell lines s100a6 overexpression independent risk factor patients survival silencing s100a6 resulted suppression proliferation p38 mapk activity overexpressing s100a6 caused promotion proliferation p38 mapk discussion s100a6 participated proliferation icc cells correlated aggressive behavior icc conclusion s100a6 may serve novel prognostic marker potential therapeutic target icc patients pubmed","probabilities":0.875,"Title":"S100A6 promotes proliferation of intrahepatic cholangiocarcinoma cells via the activation of the p38/MAPK pathway","Abstract":"AIM: We explored the expression of S100A6 and its role in intrahepatic cholangiocarcinoma (ICC). METHODS: The expression of S100A6 in ICC samples was detected by immunohistochemistry. In vitro experiments, we silenced and overexpressed S100A6 to investigate its role in cell functions. RESULTS: The expression of S100A6 was markedly increased in ICC tissues and cell lines. S100A6 overexpression was an independent risk factor for patients' survival. Silencing S100A6 resulted in a suppression of proliferation and p38/MAPK activity, while overexpressing S100A6 caused a promotion of proliferation and p38/MAPK. DISCUSSION:  S100A6 participated in the proliferation of ICC cells and correlated with a more aggressive behavior of ICC. Conclusion: S100A6 may serve as a novel prognostic marker and a potential therapeutic target for ICC patients.","Source":"PubMed","category":"ANIMAL","training_data":"S100A6 promotes proliferation of intrahepatic cholangiocarcinoma cells via the activation of the p38/MAPK pathway AIM: We explored the expression of S100A6 and its role in intrahepatic cholangiocarcinoma (ICC). METHODS: The expression of S100A6 in ICC samples was detected by immunohistochemistry. In vitro experiments, we silenced and overexpressed S100A6 to investigate its role in cell functions. RESULTS: The expression of S100A6 was markedly increased in ICC tissues and cell lines. S100A6 overexpression was an independent risk factor for patients' survival. Silencing S100A6 resulted in a suppression of proliferation and p38/MAPK activity, while overexpressing S100A6 caused a promotion of proliferation and p38/MAPK. DISCUSSION:  S100A6 participated in the proliferation of ICC cells and correlated with a more aggressive behavior of ICC. Conclusion: S100A6 may serve as a novel prognostic marker and a potential therapeutic target for ICC patients. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"prognostic value angiogenic cell proliferation immunohistochemical markers hepatocellular carcinoma cholangiocarcinoma objective analyze prognostic value immunohistochemical expression angiogenic cell proliferation markers hepatocellular carcinoma cholangiocarcinoma compare literature data method study included 110 patients hepatocellular carcinoma cholangiocarcinoma diagnosed 2000 2012 fundeni clinical institute bucharest romania results studied cases represented 28 23 0 cholangiocarcinomas 15 male 13 female mean age 54 11 average tumour size 7 73 cm 82 67 2 hepatocellular carcinoma 25 female 57 male mean age 57 62 average tumour size 4 06 cm 61 cases performed immunohistochemistry vegf 18 cases colangiocarcinoma 43 cases hepatocelular carcinoma 35 cases cd 34 9 cases colangiocarcinoma 26 cases hepatocelular carcinoma cases tested ki67 assessing differences correlations groups mentioned conclusion ki67 expressed intrahepatic cholangiocarcinoma correlated survival making promising independent prognostic immunohistochemical marker vegf expressed 95 cases hepatocellular carcinoma colangiocarcinoma cd 34 expressed 80 cases hepatocellular carcinoma versus 90 cases colangiocarcinoma resembling slight increase neovascularization google scholar","probabilities":1.0,"Title":"Prognostic Value Of Angiogenic And Cell Proliferation Immunohistochemical Markers In Hepatocellular Carcinoma And Cholangiocarcinoma","Abstract":"Objective: To analyze the prognostic value of immunohistochemical\nexpression of angiogenic and cell proliferation markers in hepatocellular\ncarcinoma and cholangiocarcinoma, and compare them with literature\ndata.\nMethod: In this study were included 110 patients with hepatocellular\ncarcinoma and cholangiocarcinoma diagnosed between 2000 and 2012\nin Fundeni Clinical Institute, Bucharest, Romania.\nResults: Studied cases were represented by 28 (23.0 %)\ncholangiocarcinomas (15 male and 13 female, mean age- 54.11, average\ntumour size- 7.73 cm) and 82 (67.2 %) hepatocellular carcinoma (25\nfemale and 57 male, mean age- 57.62, average tumour size- 4.06 cm).\nIn 61 cases was performed immunohistochemistry for VEGF (18 cases\nwith colangiocarcinoma and 43 cases with hepatocelular carcinoma) and\nin 35 cases for CD 34 (9 cases with colangiocarcinoma and 26 cases with\nhepatocelular carcinoma), all cases being tested for Ki67 with assessing\nthe differences and correlations between groups mentioned above.\nConclusion: Ki67 was over expressed in intrahepatic cholangiocarcinoma\nand it is correlated with the survival making it a promising independent\nprognostic immunohistochemical marker. VEGF was expressed in about\n95 % of cases with hepatocellular carcinoma and colangiocarcinoma, and\nCD 34 was expressed in 80 % in cases with hepatocellular carcinoma\nversus about 90 % of cases with colangiocarcinoma, resembling slight\nincrease in neovascularization.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Value Of Angiogenic And Cell Proliferation Immunohistochemical Markers In Hepatocellular Carcinoma And Cholangiocarcinoma Objective: To analyze the prognostic value of immunohistochemical\nexpression of angiogenic and cell proliferation markers in hepatocellular\ncarcinoma and cholangiocarcinoma, and compare them with literature\ndata.\nMethod: In this study were included 110 patients with hepatocellular\ncarcinoma and cholangiocarcinoma diagnosed between 2000 and 2012\nin Fundeni Clinical Institute, Bucharest, Romania.\nResults: Studied cases were represented by 28 (23.0 %)\ncholangiocarcinomas (15 male and 13 female, mean age- 54.11, average\ntumour size- 7.73 cm) and 82 (67.2 %) hepatocellular carcinoma (25\nfemale and 57 male, mean age- 57.62, average tumour size- 4.06 cm).\nIn 61 cases was performed immunohistochemistry for VEGF (18 cases\nwith colangiocarcinoma and 43 cases with hepatocelular carcinoma) and\nin 35 cases for CD 34 (9 cases with colangiocarcinoma and 26 cases with\nhepatocelular carcinoma), all cases being tested for Ki67 with assessing\nthe differences and correlations between groups mentioned above.\nConclusion: Ki67 was over expressed in intrahepatic cholangiocarcinoma\nand it is correlated with the survival making it a promising independent\nprognostic immunohistochemical marker. VEGF was expressed in about\n95 % of cases with hepatocellular carcinoma and colangiocarcinoma, and\nCD 34 was expressed in 80 % in cases with hepatocellular carcinoma\nversus about 90 % of cases with colangiocarcinoma, resembling slight\nincrease in neovascularization. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"circulating cea dnlr score predicts clinical outcome metastatic gallbladder cancer patient background cancer related inflammation promotes gallbladder tumorigenesis metastasis gallbladder cancer mgbc levels circulating inflammatory related cell protein well ratios may imply severity chronic inflammation gbc patients candidate prognostic biomarkers mgbc materials methods study pre treatment circulating immune cell fibrinogen fib albumin alb pre albumin palb detected 220 mgbc patients calculated neutrophil lymphocyte ratio nlr derived neutrophil lymphocyte ratio dnlr lymphocyte monocyte ratio lmr platelet lymphocyte ratio plr alb fib ratio afr fib palb ratio fpr replying detection three years follow carried patients investigated possible associations biomarkers three years overall survival os patients using x tile software kaplan meier curve cox regression time dependent receiver operating characteristics roc results results showed os patients high palb lmr significantly superior cases low biomarkers respectively however survival cases high cea dnlr fpr significantly inferior patients low levels biomarkers area curve auc time dependent roc cea dnlr higher palb lmr fpr respectively additionally higher cea dnlr score adjusted hr 3 09 95 ci 1 01 4 51 score one adjusted hr 4 99 95 ci 2 32 7 21 score two significantly associated reduced survival patients auc score predicting clinical outcome mgbc patients 0 756 significantly higher single cea dnlr respectively conclusion findings implied pretreatment cea dnlr score superior biomarkers predict os mgbc patients independent prognostic factor disease pubmed","probabilities":0.962963,"Title":"Circulating CEA-dNLR score predicts clinical outcome of metastatic gallbladder cancer patient","Abstract":"BACKGROUND: Cancer-related inflammation promotes gallbladder tumorigenesis and metastasis of gallbladder cancer (mGBC). The levels of circulating inflammatory-related cell and protein as well as the ratios of them may imply the severity of chronic inflammation in GBC patients, and all of them are candidate prognostic biomarkers for mGBC. MATERIALS AND METHODS: In our study, pre-treatment circulating immune cell, fibrinogen (Fib), albumin (Alb), and pre-albumin (pAlb) were detected in 220 mGBC patients, and we calculated neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Alb-to-Fib ratio (AFR), and Fib-to-pAlb ratio (FPR) replying on the detection. Three years' follow-up was carried out in those patients, and we investigated the possible associations between those biomarkers and three years' overall survival (OS) of these patients using X-tile software, Kaplan-Meier curve, Cox regression, and time-dependent receiver operating characteristics (ROC). RESULTS: Our results showed that OS of the patients with high pAlb and LMR was significantly superior to the cases with the low biomarkers, respectively. However, survival of the cases with high CEA, dNLR, and FPR was significantly inferior to the patients with low levels of those biomarkers. Area under the curve (AUC) of time-dependent ROC of CEA and dNLR was higher than pAlb, LMR, and FPR, respectively. Additionally, higher CEA-dNLR score (adjusted HR = 3.09, 95% CI = 1.01-4.51 for the score one; adjusted HR = 4.99, 95% CI = 2.32-7.21 for the score two) was significantly associated with reduced survival of the patients, and AUC of the score for predicting clinical outcome of mGBC patients was 0.756, and it was significantly higher than the single CEA and dNLR, respectively. CONCLUSION: Our findings implied that pretreatment CEA-dNLR score was superior to the other biomarkers to predict OS of mGBC patients, and it was an independent prognostic factor for the disease.","Source":"PubMed","category":"HUMAN","training_data":"Circulating CEA-dNLR score predicts clinical outcome of metastatic gallbladder cancer patient BACKGROUND: Cancer-related inflammation promotes gallbladder tumorigenesis and metastasis of gallbladder cancer (mGBC). The levels of circulating inflammatory-related cell and protein as well as the ratios of them may imply the severity of chronic inflammation in GBC patients, and all of them are candidate prognostic biomarkers for mGBC. MATERIALS AND METHODS: In our study, pre-treatment circulating immune cell, fibrinogen (Fib), albumin (Alb), and pre-albumin (pAlb) were detected in 220 mGBC patients, and we calculated neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), Alb-to-Fib ratio (AFR), and Fib-to-pAlb ratio (FPR) replying on the detection. Three years' follow-up was carried out in those patients, and we investigated the possible associations between those biomarkers and three years' overall survival (OS) of these patients using X-tile software, Kaplan-Meier curve, Cox regression, and time-dependent receiver operating characteristics (ROC). RESULTS: Our results showed that OS of the patients with high pAlb and LMR was significantly superior to the cases with the low biomarkers, respectively. However, survival of the cases with high CEA, dNLR, and FPR was significantly inferior to the patients with low levels of those biomarkers. Area under the curve (AUC) of time-dependent ROC of CEA and dNLR was higher than pAlb, LMR, and FPR, respectively. Additionally, higher CEA-dNLR score (adjusted HR = 3.09, 95% CI = 1.01-4.51 for the score one; adjusted HR = 4.99, 95% CI = 2.32-7.21 for the score two) was significantly associated with reduced survival of the patients, and AUC of the score for predicting clinical outcome of mGBC patients was 0.756, and it was significantly higher than the single CEA and dNLR, respectively. CONCLUSION: Our findings implied that pretreatment CEA-dNLR score was superior to the other biomarkers to predict OS of mGBC patients, and it was an independent prognostic factor for the disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical factors associated survival patients intrahepatic cholangiocarcinoma background aim intrahepatic cholangiocellular carcinoma icc uncommon lethal cancer aim study assess factors affecting survival icc patients evaluate benefit factors various therapeutic modalities used methods october 2007 june 2012 66 icc cases among 2255 liver cancer patients identified pathology divided two groups group surgery group n 17 group ii nonsurgery group n 49 group ii divided group iia receiving palliative treatment n 19 group iib treatment received n 30 factors affecting patient survival study period assessed 3 6 month results reported therapeutic benefits identified within groups evaluated results 66 patients identified male female 36 30 10 6 7 66 early stages illness overall mean patient survival duration 3 50 0 92 months 1 69 5 31 months mean survival duration group patients 10 50 2 84 months 4 94 16 06 months mean survival duration group ii patients 3 50 0 65 months 2 24 4 76 months group iia patients surviving average 9 50 3 27 months 3 10 15 90 months group iib patients surviving average 1 50 0 12 months 1 26 1 74 months better survival outcomes observed groups receiving treatment group group iia group iib receive treatment 9 50 1 73 months 6 12 12 89 months vs 1 50 0 12 months 1 26 1 74 months p 0 001 lower albumin higher bilirubin higher ca19 9 advanced tumor stage treatment identified important predictors patient mortality 3 6 month time points factors remained relevant throughout entire study period p 0 002 0 029 0 027 0 028 0 001 respectively conclusion study identified surgery treatment provided best survival prognosis patients icc treatment involving either chemotherapy radiotherapy also prolong icc patient survival better liver preservation lower ca19 9 less aggressive tumor conditions identified factors play crucial roles enhancing patient survival google scholar","probabilities":0.9799733,"Title":"Clinical Factors Associated With The Survival Of Patients With Intrahepatic Cholangiocarcinoma","Abstract":"Background and aim\nIntrahepatic cholangiocellular carcinoma (ICC) is an uncommon but lethal cancer. The aim of this study is to assess the factors affecting the survival of ICC patients and to evaluate the benefit of these factors when various therapeutic modalities are used.\nMethods\nBetween October 2007 and June 2012, 66 ICC cases among 2255 liver cancer patients were identified by pathology and divided into two groups: Group I (surgery group; n = 17) and Group II (nonsurgery group; n = 49). Group II was further divided into Group IIa (those receiving palliative treatment; n = 19) and Group IIb (no treatment received; n = 30). Factors affecting patient survival over the study period were assessed (3- and 6-month results were reported) and therapeutic benefits identified within each of the groups were evaluated.\nResults\nOf the 66 patients identified (male/female = 36/30), 10.6% (7/66) were in the early stages of illness. Overall, the mean patient survival duration was 3.50 ± 0.92 months (1.69–5.31 months). The mean survival duration of Group I patients was 10.50 ± 2.84 months (4.94–16.06 months). The mean survival duration of Group II patients was 3.50 ± 0.65 months (2.24–4.76 months) with Group IIa patients surviving on average 9.50 ± 3.27 months (3.10–15.90 months) and Group IIb patients surviving on average 1.50 ± 0.12 months (1.26–1.74 months). Better survival outcomes were observed in the groups receiving treatment, Group I and Group IIa, than in Group Iib, which did not receive treatment [9.50 ± 1.73 months (6.12–12.89 months) vs. 1.50 ± 0.12 months (1.26–1.74 months), p < 0.001]. Lower albumin, higher bilirubin, higher CA19-9, advanced tumor stage, and no treatment were identified as important predictors of patient mortality at the 3- and 6-month time-points. These factors remained relevant throughout the entire study period (p = 0.002, 0.029, 0.027, 0.028, < 0.001, respectively).\nConclusion\nThis study identified surgery as the treatment that provided the best survival prognosis for patients with ICC. Treatment involving either chemotherapy or radiotherapy could also prolong ICC patient survival. Better liver preservation, lower CA19-9, and less aggressive tumor conditions were identified as factors which play crucial roles in enhancing patient survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Clinical Factors Associated With The Survival Of Patients With Intrahepatic Cholangiocarcinoma Background and aim\nIntrahepatic cholangiocellular carcinoma (ICC) is an uncommon but lethal cancer. The aim of this study is to assess the factors affecting the survival of ICC patients and to evaluate the benefit of these factors when various therapeutic modalities are used.\nMethods\nBetween October 2007 and June 2012, 66 ICC cases among 2255 liver cancer patients were identified by pathology and divided into two groups: Group I (surgery group; n = 17) and Group II (nonsurgery group; n = 49). Group II was further divided into Group IIa (those receiving palliative treatment; n = 19) and Group IIb (no treatment received; n = 30). Factors affecting patient survival over the study period were assessed (3- and 6-month results were reported) and therapeutic benefits identified within each of the groups were evaluated.\nResults\nOf the 66 patients identified (male/female = 36/30), 10.6% (7/66) were in the early stages of illness. Overall, the mean patient survival duration was 3.50 ± 0.92 months (1.69–5.31 months). The mean survival duration of Group I patients was 10.50 ± 2.84 months (4.94–16.06 months). The mean survival duration of Group II patients was 3.50 ± 0.65 months (2.24–4.76 months) with Group IIa patients surviving on average 9.50 ± 3.27 months (3.10–15.90 months) and Group IIb patients surviving on average 1.50 ± 0.12 months (1.26–1.74 months). Better survival outcomes were observed in the groups receiving treatment, Group I and Group IIa, than in Group Iib, which did not receive treatment [9.50 ± 1.73 months (6.12–12.89 months) vs. 1.50 ± 0.12 months (1.26–1.74 months), p < 0.001]. Lower albumin, higher bilirubin, higher CA19-9, advanced tumor stage, and no treatment were identified as important predictors of patient mortality at the 3- and 6-month time-points. These factors remained relevant throughout the entire study period (p = 0.002, 0.029, 0.027, 0.028, < 0.001, respectively).\nConclusion\nThis study identified surgery as the treatment that provided the best survival prognosis for patients with ICC. Treatment involving either chemotherapy or radiotherapy could also prolong ICC patient survival. Better liver preservation, lower CA19-9, and less aggressive tumor conditions were identified as factors which play crucial roles in enhancing patient survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"combined treatment advanced intrahepatic cholangiocarcinoma transarterial chemoembolisation tace systemic therapy gemcitabine docetaxel background cholangiocarcinoma got poor prognosis combining locally ablative procedures systemic therapy seems one way prolonging lifetime patients advanced intrahepatic cholangiocarcinoma far standard therapy established methods prospectively data 39 patients collected 01 1998 10 2006 analyzed retrospectively treatment either tace systemic therapy combination tace 1 6ml lipiodol 5 20ml doxorubicin administered vessel supplying tumor directly cycle repeated every 4 weeks along staging ct scan progressing disease therapy changed weekly dose 1000mg m2 gemcitabine 35 mg m2 days 1 8 15 followed break one week cycle repeated every 4 weeks ct scan physical examination determined disease staging 3 cycles therapy continued disease progressed inacceptable adverse reactions occurred altogether 3 groups evolved 1 12 patients treated tace tace 2 15 patients progressive disease treated systemically initially treated tace tace v 3 12 patients treated systemically v results 1 cr 2 6 v 4 pr 10 3 2 v 11 sd 25 6 4 v 4 tace v 20 pd 51 3 7 tace 8 tace v 5 v 4 patients 10 2 staging done median survival time tace 4 16 months tace v 20 1 months 10 93 months v median time tumor progression 2 1 months tace 2 6 months tace v 5 2 months v results obtained acceptable toxicity satisfactory quality life conclusions combining tace systemic chemotherapy selected group patients progressing cholangiocarcinoma considerably prolong time survival acceptable toxicity google scholar","probabilities":0.9799733,"Title":"Combined Treatment Of Advanced Intrahepatic Cholangiocarcinoma With Transarterial Chemoembolisation (Tace) And Systemic Therapy With Gemcitabine And Docetaxel","Abstract":"Background: The cholangiocarcinoma has got a poor prognosis. Combining locally ablative procedures with systemic therapy seems to be one way of prolonging lifetime in patients with advanced intrahepatic cholangiocarcinoma. So far standard therapy has not been established. Methods: Prospectively, data of 39 patients was collected from 01/1998 to 10/2006 and analyzed retrospectively. Treatment was either TACE, systemic therapy or a combination of both. With TACE 1–6ml lipiodol and 5–20ml doxorubicin were administered into the vessel supplying the tumor directly. The cycle was repeated every 4 weeks along with a staging CT scan. In progressing disease therapy was changed to a weekly dose of 1000mg/m2 gemcitabine and 35 mg/m2 on days 1, 8 and 15, followed by a break of one week. The cycle was repeated every 4 weeks. A CT scan and physical examination determined disease staging after 3 cycles. Therapy was continued until disease progressed or inacceptable adverse reactions occurred. Altogether 3 groups evolved: 1- 12 patients treated with TACE only (tace), 2- 15 patients with progressive disease treated systemically after initially being treated with TACE (tace+i.v.), 3- 12 patients treated systemically only (i.v.). Results: There were 1 CR - 2.6% (i.v.), 4 PR- 10.3% (2 i.v.) 11 SD- 25.6% (4 i.v., 4 tace+i.v.), 20 PD- 51.3% (7 tace, 8 tace+i.v., 5 i.v.). In 4 patients (10.2%) no staging could be done. Median survival time in tace was 4.16 months, tace+i.v. 20.1 months and 10.93 months in i.v. Median time to tumor progression was 2.1 months in tace, 2.6 months in tace+i.v. and 5.2 months in i.v. Results were obtained with acceptable toxicity and satisfactory quality of life. Conclusions: Combining TACE with systemic chemotherapy in a selected group of patients with progressing cholangiocarcinoma can considerably prolong time of survival with acceptable toxicity.","Source":"Google Scholar","category":"HUMAN","training_data":"Combined Treatment Of Advanced Intrahepatic Cholangiocarcinoma With Transarterial Chemoembolisation (Tace) And Systemic Therapy With Gemcitabine And Docetaxel Background: The cholangiocarcinoma has got a poor prognosis. Combining locally ablative procedures with systemic therapy seems to be one way of prolonging lifetime in patients with advanced intrahepatic cholangiocarcinoma. So far standard therapy has not been established. Methods: Prospectively, data of 39 patients was collected from 01/1998 to 10/2006 and analyzed retrospectively. Treatment was either TACE, systemic therapy or a combination of both. With TACE 1–6ml lipiodol and 5–20ml doxorubicin were administered into the vessel supplying the tumor directly. The cycle was repeated every 4 weeks along with a staging CT scan. In progressing disease therapy was changed to a weekly dose of 1000mg/m2 gemcitabine and 35 mg/m2 on days 1, 8 and 15, followed by a break of one week. The cycle was repeated every 4 weeks. A CT scan and physical examination determined disease staging after 3 cycles. Therapy was continued until disease progressed or inacceptable adverse reactions occurred. Altogether 3 groups evolved: 1- 12 patients treated with TACE only (tace), 2- 15 patients with progressive disease treated systemically after initially being treated with TACE (tace+i.v.), 3- 12 patients treated systemically only (i.v.). Results: There were 1 CR - 2.6% (i.v.), 4 PR- 10.3% (2 i.v.) 11 SD- 25.6% (4 i.v., 4 tace+i.v.), 20 PD- 51.3% (7 tace, 8 tace+i.v., 5 i.v.). In 4 patients (10.2%) no staging could be done. Median survival time in tace was 4.16 months, tace+i.v. 20.1 months and 10.93 months in i.v. Median time to tumor progression was 2.1 months in tace, 2.6 months in tace+i.v. and 5.2 months in i.v. Results were obtained with acceptable toxicity and satisfactory quality of life. Conclusions: Combining TACE with systemic chemotherapy in a selected group of patients with progressing cholangiocarcinoma can considerably prolong time of survival with acceptable toxicity. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"associations pancreatobiliary fish assay genetic aberrations clinical characteristics outcomes patients perihilar cholangiocarcinoma background hepatocellular carcinoma hcc third common cause cancer mortality worldwide environmental risk factors include viral hepatitis excess alcohol use non alcoholic fatty liver disease nafld family history hcc increases risk independently viral hepatitis status however underlying genetic links increased risk incompletely understood sought investigate prevalence germline mutations cancer associated genes patients hcc methods google scholar","probabilities":0.9799733,"Title":"Associations Of Pancreatobiliary Fish Assay Genetic Aberrations With Clinical Characteristics And Outcomes Of Patients With Perihilar Cholangiocarcinoma","Abstract":"Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer \nmortality worldwide. Environmental risk factors include viral hepatitis, excess alcohol use, \nand non-alcoholic fatty liver disease (NAFLD). A family history of HCC increases risk \nindependently of viral hepatitis status. However, the underlying genetic links to this \nincreased risk are incompletely understood. We sought to investigate the prevalence of \ngermline mutations in cancer-associated genes in patients with HCC. Methods: We …","Source":"Google Scholar","category":"HUMAN","training_data":"Associations Of Pancreatobiliary Fish Assay Genetic Aberrations With Clinical Characteristics And Outcomes Of Patients With Perihilar Cholangiocarcinoma Background: Hepatocellular carcinoma (HCC) is the third most common cause of cancer \nmortality worldwide. Environmental risk factors include viral hepatitis, excess alcohol use, \nand non-alcoholic fatty liver disease (NAFLD). A family history of HCC increases risk \nindependently of viral hepatitis status. However, the underlying genetic links to this \nincreased risk are incompletely understood. We sought to investigate the prevalence of \ngermline mutations in cancer-associated genes in patients with HCC. Methods: We … Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"effectiveness safety sorafenib unresectable advanced intrahepatic cholangiocarcinoma pilot study patients unresectable advanced intrahepatic cholangiocarcinoma icc usually short survival due lack effective treatment multicenter single arm open labeled prospective study conducted evaluate effectiveness safety sorafenib combined best supportive care bsc patients enrolled 44 patients unresectable advanced icc treated sorafenib 400 mg twice daily bsc primary endpoint disease control rate dcr week 12 secondary endpoints included time progression ttp progression free survival pfs overall survival os duration therapy dot adverse events aes results showed dcr 15 9 median ttp 5 6 months median pfs os 3 2 5 7 months 95 confidence interval ci 2 4 4 1 months 3 7 8 5 months respectively median dot 1 8 months 95 ci 1 9 3 9 months aes grades 1 2 events occurred 75 patients ae grade 4 severe observed 1 patient therefore sorafenib combination bsc acceptable dcr safety profile patients unresectable advanced icc stn","probabilities":0.9799733,"Title":"Effectiveness And Safety Of Sorafenib For Unresectable And Advanced Intrahepatic Cholangiocarcinoma: A Pilot Study","Abstract":"Patients with unresectable and advanced intrahepatic cholangiocarcinoma (ICC) usually have short survival due to a lack of effective treatment. This multicenter, single arm, open labeled, prospective study was conducted to evaluate the effectiveness and safety of sorafenib combined with best supportive care (BSC) in these patients. We enrolled 44 patients with unresectable and advanced ICC who were treated with sorafenib (400 mg, twice daily) and BSC. The primary endpoint was disease control rate (DCR) at week 12, and the secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), duration of therapy (DOT), and adverse events (AEs). Our results showed that the DCR was 15.9%, the median TTP was 5.6 months, and the median PFS and OS were 3.2 and 5.7 months (95% confidence interval [CI]: 2.4-4.1 months; 3.7-8.5 months), respectively. The median DOT was 1.8 months (95% CI: 1.9-3.9 months). AEs of grades 1 and 2 events occurred in 75% of patients, and AE of grade 4 (severe) was observed in 1 patient. Therefore, sorafenib in combination with BSC had an acceptable DCR and safety profile in patients with unresectable and advanced ICC.","Source":"STN","category":"HUMAN","training_data":"Effectiveness And Safety Of Sorafenib For Unresectable And Advanced Intrahepatic Cholangiocarcinoma: A Pilot Study Patients with unresectable and advanced intrahepatic cholangiocarcinoma (ICC) usually have short survival due to a lack of effective treatment. This multicenter, single arm, open labeled, prospective study was conducted to evaluate the effectiveness and safety of sorafenib combined with best supportive care (BSC) in these patients. We enrolled 44 patients with unresectable and advanced ICC who were treated with sorafenib (400 mg, twice daily) and BSC. The primary endpoint was disease control rate (DCR) at week 12, and the secondary endpoints included time to progression (TTP), progression-free survival (PFS), overall survival (OS), duration of therapy (DOT), and adverse events (AEs). Our results showed that the DCR was 15.9%, the median TTP was 5.6 months, and the median PFS and OS were 3.2 and 5.7 months (95% confidence interval [CI]: 2.4-4.1 months; 3.7-8.5 months), respectively. The median DOT was 1.8 months (95% CI: 1.9-3.9 months). AEs of grades 1 and 2 events occurred in 75% of patients, and AE of grade 4 (severe) was observed in 1 patient. Therefore, sorafenib in combination with BSC had an acceptable DCR and safety profile in patients with unresectable and advanced ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"tumor location independent predictor malignant potency superficial non ampullary duodenal epithelial tumors abstract available google scholar","probabilities":0.9799733,"Title":"Tumor Location Is An Independent Predictor For Malignant Potency Of Superficial Non-Ampullary Duodenal Epithelial Tumors","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Tumor Location Is An Independent Predictor For Malignant Potency Of Superficial Non-Ampullary Duodenal Epithelial Tumors Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic role neutrophil lymphocyte ratio nlr patients operable ampullary carcinoma ampullary carcinoma cancer ampulla vater rare malignancy high recurrence rate although cost effective biomarkers neutrophil lymphocyte ratio nlr investigated cancers predicting postoperative prognosis patients studies role nlr ampullary cancer scarce aimed evaluate prognostic significance preoperative nlr patients operable ampullary carcinoma retrospectively reviewed 87 patients underwent pancreaticoduodenectomy treatment ampullary carcinoma december 1999 april 2014 association nlr prognosis overall survival os disease free survival dfs evaluated possible correlations nlr clinicopathological features also assessed 5 year dfs os rates surgery patients ampullary carcinoma 51 63 respectively high nlr 3 0 found 40 patients nlr significant prognostic factor os dfs multivariate analysis revealed significantly worse os patients positive surgical margins nlr 3 p 0 001 patients t3 t4 stage p 0 029 nlr 3 p 0 043 lower dfs patients high nlr significantly worse eastern cooperative oncology group performance score preoperative nlr independent significant predictive factor prognosis patients ampullary carcinoma elevated pretreatment nlr e g nlr 3 may considered biomarker poor prognosis patients ampullary carcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic role of neutrophil-to-lymphocyte ratio (NLR) in patients with operable ampullary carcinoma","Abstract":"Ampullary carcinoma or cancer of the ampulla of Vater is a rare malignancy with a high recurrence rate. Although cost-effective biomarkers, such as neutrophil-to-lymphocyte ratio (NLR), have been investigated in other cancers for predicting postoperative prognosis in patients, studies on the role of NLR in ampullary cancer are scarce. Here we aimed to evaluate the prognostic significance of preoperative NLR in patients with operable ampullary carcinoma. We retrospectively reviewed 87 patients who underwent pancreaticoduodenectomy for the treatment of ampullary carcinoma between December 1999 and April 2014. The association between NLR and prognosis (overall survival [OS] and disease-free survival [DFS]) was evaluated. Possible correlations between NLR and clinicopathological features were also assessed. The 5-year DFS and OS rates after surgery in patients with ampullary carcinoma were 51% and 63%, respectively. A high NLR (≥3.0) was found in 40 patients. The NLR was a significant prognostic factor for both OS and DFS. Multivariate analysis revealed a significantly worse OS in patients with positive surgical margins and NLR ≥3 (p = 0.001). Patients with T3-T4 stage (p = 0.029) and NLR ≥3 (p = 0.043) had a lower DFS. Patients with a high NLR had a significantly worse Eastern Cooperative Oncology Group performance score. Preoperative NLR is an independent and significant predictive factor of prognosis in patients with ampullary carcinoma. An elevated pretreatment NLR (e.g., NLR ≥3) may be considered as a biomarker for poor prognosis in patients with ampullary carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic role of neutrophil-to-lymphocyte ratio (NLR) in patients with operable ampullary carcinoma Ampullary carcinoma or cancer of the ampulla of Vater is a rare malignancy with a high recurrence rate. Although cost-effective biomarkers, such as neutrophil-to-lymphocyte ratio (NLR), have been investigated in other cancers for predicting postoperative prognosis in patients, studies on the role of NLR in ampullary cancer are scarce. Here we aimed to evaluate the prognostic significance of preoperative NLR in patients with operable ampullary carcinoma. We retrospectively reviewed 87 patients who underwent pancreaticoduodenectomy for the treatment of ampullary carcinoma between December 1999 and April 2014. The association between NLR and prognosis (overall survival [OS] and disease-free survival [DFS]) was evaluated. Possible correlations between NLR and clinicopathological features were also assessed. The 5-year DFS and OS rates after surgery in patients with ampullary carcinoma were 51% and 63%, respectively. A high NLR (≥3.0) was found in 40 patients. The NLR was a significant prognostic factor for both OS and DFS. Multivariate analysis revealed a significantly worse OS in patients with positive surgical margins and NLR ≥3 (p = 0.001). Patients with T3-T4 stage (p = 0.029) and NLR ≥3 (p = 0.043) had a lower DFS. Patients with a high NLR had a significantly worse Eastern Cooperative Oncology Group performance score. Preoperative NLR is an independent and significant predictive factor of prognosis in patients with ampullary carcinoma. An elevated pretreatment NLR (e.g., NLR ≥3) may be considered as a biomarker for poor prognosis in patients with ampullary carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"perineural infiltration prognostic factor surgically treated gallbladder cancer single center experience literature review introduction gallbladder cancer gbc incident cancer biliary tract 5 13 sufferers surviving five years aim study evaluate prognostic role perineural invasion pni association several clinicopathological variables cohort surgically treated patients comprehensive review scientific literature materials methods twenty five consecutive patients submitted curative surgery gbc 2008 2016 enrolled demographic clinical pathological data retrieved medical files specimens re examined two experienced pathologists pubmed database searched articles reporting perineural infiltration gallbladder cancer results perineural invasion observed 14 56 cases frequent higher pathological stages statistically significant association found high preoperative serum ca 19 9 levels fourteen 56 patients died follow survival lower patients perineural invasion comparison without statistically significant twelve english language articles reporting pni retrieved discussed conclusions perineural invasion associated higher stage poorer survival surgically treated gbc patients patients locally advanced gbc resection extrahepatic biliary duct frozen section examination distal stump must taken consideration especially cases tumor arising hepatic side gallbladder cases without residual disease pathological evidence pni careful follow suggested early detect recurrences key words adenocarcinoma cancer gallbladder perineural infiltration surgery pubmed","probabilities":0.9799733,"Title":"Perineural infiltration as a prognostic factor in surgically treated gallbladder cancer A single center experience and literature review","Abstract":"INTRODUCTION: Gallbladder cancer (GBC) is the most incident cancer of the biliary tract with only 5-13% of the sufferers surviving for five years. The aim of this study was to evaluate the prognostic role of perineural invasion (PNI) and its association with several clinicopathological variables in a cohort of surgically treated patients, and through a comprehensive review of the scientific literature. MATERIALS AND METHODS: Twenty-five consecutive patients submitted to curative surgery for GBC from 2008 through 2016 were enrolled. Demographic, clinical and pathological data were retrieved from medical files, and specimens were re-examined by two experienced pathologists. The Pubmed database was searched for articles reporting on perineural infiltration on gallbladder cancer. RESULTS: Perineural invasion was observed in 14 (56%) cases, and it was more frequent in higher pathological stages. A statistically significant association was found with high preoperative serum Ca 19-9 levels. Fourteen (56%) patients died during the follow-up; survival was lower in patients with perineural invasion in comparison to those without, but not statistically significant. Twelve English-language articles reporting on PNI were retrieved and discussed. CONCLUSIONS: Perineural invasion is associated with higher stage and poorer survival in surgically treated GBC patients. In patients with locally advanced GBC resection of the extrahepatic biliary duct and frozen section examination of the distal stump must be taken into consideration, especially in cases of tumor arising from the hepatic side of the gallbladder. In cases without residual disease but with pathological evidence of PNI, a careful follow-up is suggested to early detect recurrences. KEY WORDS: Adenocarcinoma, Cancer, Gallbladder, Perineural infiltration, Surgery.","Source":"PubMed","category":"HUMAN","training_data":"Perineural infiltration as a prognostic factor in surgically treated gallbladder cancer A single center experience and literature review INTRODUCTION: Gallbladder cancer (GBC) is the most incident cancer of the biliary tract with only 5-13% of the sufferers surviving for five years. The aim of this study was to evaluate the prognostic role of perineural invasion (PNI) and its association with several clinicopathological variables in a cohort of surgically treated patients, and through a comprehensive review of the scientific literature. MATERIALS AND METHODS: Twenty-five consecutive patients submitted to curative surgery for GBC from 2008 through 2016 were enrolled. Demographic, clinical and pathological data were retrieved from medical files, and specimens were re-examined by two experienced pathologists. The Pubmed database was searched for articles reporting on perineural infiltration on gallbladder cancer. RESULTS: Perineural invasion was observed in 14 (56%) cases, and it was more frequent in higher pathological stages. A statistically significant association was found with high preoperative serum Ca 19-9 levels. Fourteen (56%) patients died during the follow-up; survival was lower in patients with perineural invasion in comparison to those without, but not statistically significant. Twelve English-language articles reporting on PNI were retrieved and discussed. CONCLUSIONS: Perineural invasion is associated with higher stage and poorer survival in surgically treated GBC patients. In patients with locally advanced GBC resection of the extrahepatic biliary duct and frozen section examination of the distal stump must be taken into consideration, especially in cases of tumor arising from the hepatic side of the gallbladder. In cases without residual disease but with pathological evidence of PNI, a careful follow-up is suggested to early detect recurrences. KEY WORDS: Adenocarcinoma, Cancer, Gallbladder, Perineural infiltration, Surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"egfr cox2 p akt expression pik3ca mutation distal extrahepatic bile duct carcinoma distal extrahepatic bile duct ebd carcinoma rare highly aggressive malignant neoplasm vitro studies shown egfr pi3k akt pathway play important role carcinogenesis bile duct carcinoma aim present study investigate expression egfr p akt cox 2 mutation pik3ca distal ebd carcinoma evaluate association clinicopathological factors ninety cases distal extrahepatic bile duct ebd carcinoma specimens studied immunohistochemistry ihc using antibodies egfr p akt cox 2 performed tma blocks pik3ca mutation evaluated using pnaclamp detection kit dna samples extracted formalin fixed paraffin embedded tissue egfr expression distal ebd carcinomas 61 9 26 2 6 0 6 0 negative weakly positive moderately positive strongly positive groups respectively positive egfr expression showed significant relationships high stage p 0 024 kaplan meier analysis egfr expression associated shorter cancer specific overall survival p 0 005 multivariate analysis also showed moderate strong 2 3 egfr expression significant prognostic factor distal ebd carcinoma hr 5 286 p 0 001 ninety cases ebd carcinoma tissue analysed hotspot mutations exon 9 20 pik3ca gene one mutation detected missense mutation h1047 exon 20 expression levels p akt cox 2 showed association clinicopathological parameters including survival rate moderate strong egfr expressions demonstrate direct link poor prognosis although study warranted understand clinicopathological significance finding suggests egfr useful prognostic marker patients distal ebd carcinoma low prevalence pik3ca mutation exists distal ebd carcinoma korean patients indicating mutation screening may useful determining prognosis formulating treatment response targeted inhibition korea pubmed","probabilities":0.875,"Title":"EGFR, COX2, p-AKT expression and PIK3CA mutation in distal extrahepatic bile duct carcinoma","Abstract":"Distal extrahepatic bile duct (EBD) carcinoma is a rare but highly aggressive malignant neoplasm. Some in vitro studies have shown that EGFR and PI3K-Akt pathway play an important role in the carcinogenesis of bile duct carcinoma. The aim of the present study is to investigate the expression of EGFR, p-AKT, and COX-2 and the mutation of PIK3CA in distal EBD carcinoma and evaluate the association with clinicopathological factors. Ninety cases of distal extrahepatic bile duct (EBD) carcinoma specimens were studied. Immunohistochemistry (IHC) using antibodies against EGFR, p-AKT, and COX-2 was performed on TMA blocks. The PIK3CA mutation was evaluated using the PNAClamp Detection Kit from DNA samples extracted from formalin fixed, paraffin embedded tissue. EGFR expression of distal EBD carcinomas was 61.9%, 26.2%, 6.0% and 6.0% in the negative, weakly positive, moderately positive, and strongly positive groups, respectively. Positive EGFR expression showed significant relationships with high T stage (p = 0.024). In Kaplan-Meier analysis, EGFR expression was associated with shorter cancer-specific overall survival (p = 0.005). Multivariate analysis also showed that moderate or strong (2+ or 3+) EGFR expression was a significant prognostic factor in distal EBD carcinoma: HR 5.286; p = 0.001. Ninety cases of EBD carcinoma tissue were analysed for hotspot mutations (exon 9 and 20) in the PIK3CA gene. Only one mutation was detected: a missense mutation of H1047 at exon 20. The expression levels of p-AKT and COX-2 showed no association with any clinicopathological parameters, including survival rate. Moderate and strong EGFR expressions demonstrate a direct link to poor prognosis. Although further study is warranted to understand the clinicopathological significance, our finding suggests EGFR is a useful prognostic marker of patients with distal EBD carcinoma. A low prevalence of PIK3CA mutation exists in the distal EBD carcinoma of Korean patients, indicating that mutation screening may not be useful in determining prognosis or in formulating a treatment response to targeted inhibition in Korea.","Source":"PubMed","category":"ANIMAL","training_data":"EGFR, COX2, p-AKT expression and PIK3CA mutation in distal extrahepatic bile duct carcinoma Distal extrahepatic bile duct (EBD) carcinoma is a rare but highly aggressive malignant neoplasm. Some in vitro studies have shown that EGFR and PI3K-Akt pathway play an important role in the carcinogenesis of bile duct carcinoma. The aim of the present study is to investigate the expression of EGFR, p-AKT, and COX-2 and the mutation of PIK3CA in distal EBD carcinoma and evaluate the association with clinicopathological factors. Ninety cases of distal extrahepatic bile duct (EBD) carcinoma specimens were studied. Immunohistochemistry (IHC) using antibodies against EGFR, p-AKT, and COX-2 was performed on TMA blocks. The PIK3CA mutation was evaluated using the PNAClamp Detection Kit from DNA samples extracted from formalin fixed, paraffin embedded tissue. EGFR expression of distal EBD carcinomas was 61.9%, 26.2%, 6.0% and 6.0% in the negative, weakly positive, moderately positive, and strongly positive groups, respectively. Positive EGFR expression showed significant relationships with high T stage (p = 0.024). In Kaplan-Meier analysis, EGFR expression was associated with shorter cancer-specific overall survival (p = 0.005). Multivariate analysis also showed that moderate or strong (2+ or 3+) EGFR expression was a significant prognostic factor in distal EBD carcinoma: HR 5.286; p = 0.001. Ninety cases of EBD carcinoma tissue were analysed for hotspot mutations (exon 9 and 20) in the PIK3CA gene. Only one mutation was detected: a missense mutation of H1047 at exon 20. The expression levels of p-AKT and COX-2 showed no association with any clinicopathological parameters, including survival rate. Moderate and strong EGFR expressions demonstrate a direct link to poor prognosis. Although further study is warranted to understand the clinicopathological significance, our finding suggests EGFR is a useful prognostic marker of patients with distal EBD carcinoma. A low prevalence of PIK3CA mutation exists in the distal EBD carcinoma of Korean patients, indicating that mutation screening may not be useful in determining prognosis or in formulating a treatment response to targeted inhibition in Korea. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"sex ethnic racial specific risk factors gallbladder disease background gallbladder disease gbd highly prevalent condition however little known potential differences risk factors sex ethnicity race aim evaluate dietary reproductive obesity related factors gbd multiethnic populations methods performed prospective analysis multiethnic cohort study self identified non hispanic white n 32 103 african american n 30 209 japanese n 35 987 native hawaiian n 6942 latino n 39 168 gbd cases identified using medicare california hospital discharge files 1993 2012 self completed questionnaires used exposure information baseline questionnaire identify exposures interest associations estimated hazard ratios 95 confidence intervals using cox models adjusted confounders result median 10 7 years follow 13 437 gbd cases bmi 25 kg m 2 diabetes past current smoking red meat consumption saturated fat cholesterol significant risk factors across ethnic racial populations p trends 0 01 protective factors included vigorous physical activity alcohol use fruits vegetables foods rich dietary fiber p trends 0 01 carbohydrates inversely associated gbd risk among women latinos born south america mexico p trend 0 003 parity significant risk factor among women post menopausal hormones use associated increased risk among white women estrogen hr 1 24 95 ci 1 07 1 43 estrogen progesterone hr 1 23 95 ci 1 06 1 42 conclusion overall dietary reproductive obesity related factors strong risk factors gbd affecting men women different ethnicities races however risk factors appear stronger women certain ethnic groups pubmed","probabilities":0.9799733,"Title":"Sex and ethnic/racial-specific risk factors for gallbladder disease","Abstract":"BACKGROUND: Gallbladder disease (GBD) is a highly prevalent condition; however, little is known about potential differences in risk factors by sex and ethnicity/race. Our aim was to evaluate dietary, reproductive and obesity-related factors and GBD in multiethnic populations. METHODS: We performed a prospective analysis from the Multiethnic Cohort study who self-identified as non-Hispanic White (n = 32,103), African American (n = 30,209), Japanese (n = 35,987), Native Hawaiian (n = 6942) and Latino (n = 39,168). GBD cases were identified using Medicare and California hospital discharge files (1993-2012) and self-completed questionnaires. We used exposure information on the baseline questionnaire to identify exposures of interest. Associations were estimated by hazard ratios and 95% confidence intervals using Cox models adjusted for confounders. RESULT: After a median 10.7 years of follow-up, there were 13,437 GBD cases. BMI over 25 kg/m(2), diabetes, past and current smoking, red meat consumption, saturated fat and cholesterol were significant risk factors across ethnic/racial populations (p-trends < 0.01). Protective factors included vigorous physical activity, alcohol use, fruits, vegetables and foods rich in dietary fiber (p-trends < 0.01). Carbohydrates were inversely associated with GBD risk only among women and Latinos born in South America/Mexico (p-trend < 0.003). Parity was a significant risk factor among women; post-menopausal hormones use was only associated with an increased risk among White women (estrogen-only: HR = 1.24; 95% CI = 1.07-1.43 and estrogen + progesterone: HR = 1.23; 95% CI = 1.06-1.42). CONCLUSION: Overall, dietary, reproductive and obesity-related factors are strong risk factors for GBD affecting men and women of different ethnicities/races; however some risk factors appear stronger in women and certain ethnic groups.","Source":"PubMed","category":"HUMAN","training_data":"Sex and ethnic/racial-specific risk factors for gallbladder disease BACKGROUND: Gallbladder disease (GBD) is a highly prevalent condition; however, little is known about potential differences in risk factors by sex and ethnicity/race. Our aim was to evaluate dietary, reproductive and obesity-related factors and GBD in multiethnic populations. METHODS: We performed a prospective analysis from the Multiethnic Cohort study who self-identified as non-Hispanic White (n = 32,103), African American (n = 30,209), Japanese (n = 35,987), Native Hawaiian (n = 6942) and Latino (n = 39,168). GBD cases were identified using Medicare and California hospital discharge files (1993-2012) and self-completed questionnaires. We used exposure information on the baseline questionnaire to identify exposures of interest. Associations were estimated by hazard ratios and 95% confidence intervals using Cox models adjusted for confounders. RESULT: After a median 10.7 years of follow-up, there were 13,437 GBD cases. BMI over 25 kg/m(2), diabetes, past and current smoking, red meat consumption, saturated fat and cholesterol were significant risk factors across ethnic/racial populations (p-trends < 0.01). Protective factors included vigorous physical activity, alcohol use, fruits, vegetables and foods rich in dietary fiber (p-trends < 0.01). Carbohydrates were inversely associated with GBD risk only among women and Latinos born in South America/Mexico (p-trend < 0.003). Parity was a significant risk factor among women; post-menopausal hormones use was only associated with an increased risk among White women (estrogen-only: HR = 1.24; 95% CI = 1.07-1.43 and estrogen + progesterone: HR = 1.23; 95% CI = 1.06-1.42). CONCLUSION: Overall, dietary, reproductive and obesity-related factors are strong risk factors for GBD affecting men and women of different ethnicities/races; however some risk factors appear stronger in women and certain ethnic groups. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma update future perspectives cholangiocarcinoma commonly considered rare cancer however consider hepato biliary system single entity cancers gallbladder intra hepatic extra hepatic biliary tree altogether represent approximately 30 total incidence rates close hepatocellular carcinoma third common cause cancer related death worldwide addition cholangiocarcinoma characterized poor prognosis virtually response chemotherapeutics radical surgery effective treatment frequently applicable late diagnosis biomarkers screening programs follow categories risk investigation however currently none proposed markers reached clinical application considerations cancers biliary tree system merit much scientific attention also progressive increase incidence mortality cancers reported worldwide manuscript deals recent advances epidemiology biology clinical presentation cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Cholangiocarcinoma: Update And Future Perspectives","Abstract":"Cholangiocarcinoma is commonly considered a rare cancer. However, if we consider the hepato-biliary system a single entity, cancers of the gallbladder, intra-hepatic and extra-hepatic biliary tree altogether represent approximately 30% of the total with incidence rates close to that of hepatocellular carcinoma, which is the third most common cause of cancer-related death worldwide. In addition, cholangiocarcinoma is characterized by a very poor prognosis and virtually no response to chemotherapeutics; radical surgery, the only effective treatment, is not frequently applicable because late diagnosis. Biomarkers for screening programs and for follow-up of categories at risk are under investigation, however, currently none of the proposed markers has reached clinical application. For all these considerations, cancers of the biliary tree system should merit much more scientific attention also because a progressive increase in incidence and mortality for these cancers has been reported worldwide. This manuscript deals with the most recent advances in the epidemiology, biology and clinical presentation of cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Cholangiocarcinoma: Update And Future Perspectives Cholangiocarcinoma is commonly considered a rare cancer. However, if we consider the hepato-biliary system a single entity, cancers of the gallbladder, intra-hepatic and extra-hepatic biliary tree altogether represent approximately 30% of the total with incidence rates close to that of hepatocellular carcinoma, which is the third most common cause of cancer-related death worldwide. In addition, cholangiocarcinoma is characterized by a very poor prognosis and virtually no response to chemotherapeutics; radical surgery, the only effective treatment, is not frequently applicable because late diagnosis. Biomarkers for screening programs and for follow-up of categories at risk are under investigation, however, currently none of the proposed markers has reached clinical application. For all these considerations, cancers of the biliary tree system should merit much more scientific attention also because a progressive increase in incidence and mortality for these cancers has been reported worldwide. This manuscript deals with the most recent advances in the epidemiology, biology and clinical presentation of cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"simvastatin stimulates apoptosis cholangiocarcinoma inhibition rac1 activity background simvastatin cholesterol lowering drug widely used prevent treat atherosclerotic cardiovascular disease simvastatin exhibits numerous pleiotropic effects including anti cancer activity however effect simvastatin cholangiocarcinoma evaluated aim aim study determine effect simvastatin cholangiocarcinoma proliferation methods effect simvastatin evaluated five human cholangiocarcinoma cell lines mz cha 1 huh 28 tfk 1 sg231 hucct1 normal cholangiocyte cell line hibepic results found simvastatin stimulates reduction cell viability apoptosis cholangiocarcinoma cell lines whilst normal human cholangiocytes hibepic simvastatin inhibits proliferation effect apoptosis simvastatin induced reduction cell viability partially blocked pre treatment metabolites mevalonate pathway mz cha 1 cells pre treatment cholesterol alone stimulated increase number viable cells fully restored cell viability following simvastatin treatment treatment simvastatin triggered loss lipid raft localised rac1 reduction rac1 activity mz cha 1 cells effect prevented pre treatment cholesterol conclusion collectively results demonstrate simvastatin induces cholangiocarcinoma cancer cell death disrupting rac1 lipid raft colocalisation depression rac1 activity stn","probabilities":1.0,"Title":"Simvastatin Stimulates Apoptosis In Cholangiocarcinoma By Inhibition Of Rac1 Activity","Abstract":"Background: Simvastatin is a cholesterol-lowering drug that is widely used to prevent and treat atherosclerotic cardiovascular disease. Simvastatin exhibits numerous pleiotropic effects including anti-cancer activity. However, the effect of simvastatin on cholangiocarcinoma has not been evaluated. \r\n\r\n Aim: The aim of our study was to determine the effect of simvastatin on cholangiocarcinoma proliferation. \r\n\r\n Methods: The effect of simvastatin was evaluated in five human cholangiocarcinoma cell lines (Mz-ChA-1, HuH-28, TFK-1, SG231, and HuCCT1) and normal cholangiocyte cell line (HiBEpiC). \r\n\r\n Results: We found that simvastatin stimulates a reduction in cell viability and apoptosis of cholangiocarcinoma cell lines, whilst in normal human cholangiocytes, HiBEpiC, simvastatin inhibits proliferation with no effect on apoptosis. Simvastatin-induced reduction of cell viability was partially blocked by pre-treatment with metabolites of the mevalonate pathway. In Mz-ChA-1 cells, pre-treatment with cholesterol alone stimulated an increase in the number of viable cells and fully restored cell viability following simvastatin treatment. Treatment with simvastatin triggered the loss of lipid raft localised Rac1 and reduction of Rac1 activity in Mz-ChA-1 cells. This effect was prevented by pre-treatment with cholesterol. \r\n\r\n Conclusion: Collectively, our results demonstrate that simvastatin induces cholangiocarcinoma cancer cell death by disrupting Rac1/lipid raft colocalisation and depression of Rac1 activity.","Source":"STN","category":"ANIMAL","training_data":"Simvastatin Stimulates Apoptosis In Cholangiocarcinoma By Inhibition Of Rac1 Activity Background: Simvastatin is a cholesterol-lowering drug that is widely used to prevent and treat atherosclerotic cardiovascular disease. Simvastatin exhibits numerous pleiotropic effects including anti-cancer activity. However, the effect of simvastatin on cholangiocarcinoma has not been evaluated. \r\n\r\n Aim: The aim of our study was to determine the effect of simvastatin on cholangiocarcinoma proliferation. \r\n\r\n Methods: The effect of simvastatin was evaluated in five human cholangiocarcinoma cell lines (Mz-ChA-1, HuH-28, TFK-1, SG231, and HuCCT1) and normal cholangiocyte cell line (HiBEpiC). \r\n\r\n Results: We found that simvastatin stimulates a reduction in cell viability and apoptosis of cholangiocarcinoma cell lines, whilst in normal human cholangiocytes, HiBEpiC, simvastatin inhibits proliferation with no effect on apoptosis. Simvastatin-induced reduction of cell viability was partially blocked by pre-treatment with metabolites of the mevalonate pathway. In Mz-ChA-1 cells, pre-treatment with cholesterol alone stimulated an increase in the number of viable cells and fully restored cell viability following simvastatin treatment. Treatment with simvastatin triggered the loss of lipid raft localised Rac1 and reduction of Rac1 activity in Mz-ChA-1 cells. This effect was prevented by pre-treatment with cholesterol. \r\n\r\n Conclusion: Collectively, our results demonstrate that simvastatin induces cholangiocarcinoma cancer cell death by disrupting Rac1/lipid raft colocalisation and depression of Rac1 activity. STN","prediction_labels":"ANIMAL"},{"cleaned":"adjuvant chemoradiation resected gallbladder cancer prognostic model overall survival purpose patients gallbladder cancer gbc dismal prognosis investigated outcomes risk factors overall survival os patients treated radical surgery adjuvant chemoradiotherapy crt materials methods total 212 patients lagc pt3 59 pn 52 studied primary endpoint analysis os constructed risk scoring system points assigned risk factor dividing coefficient final model lowest coefficient rounding nearest integer risk score assigned subject adding points risk factor present subjects divided three risk groups based risk scores 0 points low risk 1 2 points intermediate risk 3 6 points high risk results median follow 46 2 months 2 235 five year os entire cohort 53 multivariate analysis higher pt stage hr 2 43 1 29 3 68 p 0 01 r1 resection hr 5 06 3 12 8 19 p 0 001 number surgical procedures hr 1 41 1 01 2 16 p 0 05 associated increased risk death five year os patients low n 63 intermediate n 94 high n 55 risk 79 1 51 2 9 5 respectively conclusion overall results multimodality treatment gbc promising risk model generated determine prognostic index individual patients gbc classification risk factors death contributed propose prognostic index allow us guide risk adapted tailored treatment google scholar","probabilities":0.9799733,"Title":"Adjuvant Chemoradiation In Resected Gallbladder Cancer: A Prognostic Model For Overall Survival","Abstract":"Purpose\nPatients with gallbladder cancer (GBC) have a dismal prognosis. We investigated outcomes and risk factors for overall survival (OS) in patients treated with radical surgery and adjuvant chemoradiotherapy (CRT).\nMaterials/methods\nA total of 212 patients with LAGC (⩾pT3 59% and/or pN+ 52%) were studied. The primary endpoint of the analysis was OS. We constructed a risk scoring system in which points were assigned to each risk factor by dividing each β coefficient in the final model by the lowest β coefficient and rounding to the nearest integer. A risk score was assigned to each subject by adding up the points for each risk factor present. Subjects were then divided into three risk groups based on their risk scores (0 points = low risk, 1–2 points = intermediate risk, 3–6 points = high risk).\nResults\nMedian follow-up was 46.2 months (2–235). Five-year OS for the entire cohort was 53%. In multivariate analysis, higher pT stage [HR, 2.43 (1.29–3.68); p = 0.01], R1 resection [HR, 5.06 (3.12–8.19); p < 0.001], and number of surgical procedures [HR, 1.41 (1.01–2.16); p = 0.05] were associated with an increased risk of death. Five-year OS for patients with low (n = 63), intermediate (n = 94), and high (n = 55) risk was 79.1%, 51.2%, and 9.5%, respectively.\nConclusion\nOverall results after multimodality treatment of GBC are promising. A risk model was generated to determine a prognostic index for individual patients with GBC. Classification of risk factors for death has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment.","Source":"Google Scholar","category":"HUMAN","training_data":"Adjuvant Chemoradiation In Resected Gallbladder Cancer: A Prognostic Model For Overall Survival Purpose\nPatients with gallbladder cancer (GBC) have a dismal prognosis. We investigated outcomes and risk factors for overall survival (OS) in patients treated with radical surgery and adjuvant chemoradiotherapy (CRT).\nMaterials/methods\nA total of 212 patients with LAGC (⩾pT3 59% and/or pN+ 52%) were studied. The primary endpoint of the analysis was OS. We constructed a risk scoring system in which points were assigned to each risk factor by dividing each β coefficient in the final model by the lowest β coefficient and rounding to the nearest integer. A risk score was assigned to each subject by adding up the points for each risk factor present. Subjects were then divided into three risk groups based on their risk scores (0 points = low risk, 1–2 points = intermediate risk, 3–6 points = high risk).\nResults\nMedian follow-up was 46.2 months (2–235). Five-year OS for the entire cohort was 53%. In multivariate analysis, higher pT stage [HR, 2.43 (1.29–3.68); p = 0.01], R1 resection [HR, 5.06 (3.12–8.19); p < 0.001], and number of surgical procedures [HR, 1.41 (1.01–2.16); p = 0.05] were associated with an increased risk of death. Five-year OS for patients with low (n = 63), intermediate (n = 94), and high (n = 55) risk was 79.1%, 51.2%, and 9.5%, respectively.\nConclusion\nOverall results after multimodality treatment of GBC are promising. A risk model was generated to determine a prognostic index for individual patients with GBC. Classification of risk factors for death has contributed to propose a prognostic index that could allow us to guide risk-adapted tailored treatment. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"verification oncologic inferiority percutaneous biliary drainage endoscopic drainage propensity score matching analysis resectable perihilar cholangiocarcinoma background percutaneous transhepatic biliary drainage established biliary drainage method associated potential risk seeding metastasis aim retrospective study evaluate whether percutaneous transhepatic biliary drainage really increases seeding metastasis worsens postoperative survival patients resectable perihilar cholangiocarcinoma methods patients underwent resection perihilar cholangiocarcinoma percutaneous transhepatic biliary drainage endoscopic biliary drainage retrospectively reviewed seeding metastasis defined peritoneal pleural dissemination percutaneous transhepatic biliary drainage sinus tract recurrence univariate multivariate analyses followed propensity score matching performed adjust data baseline characteristics percutaneous transhepatic biliary drainage endoscopic biliary drainage patients results 320 resected patients 168 underwent percutaneous transhepatic biliary drainage remaining 152 received endoscopic biliary drainage operation survival percutaneous transhepatic biliary drainage patients significantly lower endoscopic biliary drainage patients 37 0 vs 44 3 5 years p 019 multivariate analyses showed percutaneous transhepatic biliary drainage independent predictor poor survival p 011 risk factor seeding metastasis p 005 propensity score matching 71 patients group survival percutaneous transhepatic biliary drainage patients significantly worse endoscopic biliary drainage patients p 018 estimated cumulative recurrence rate seeding metastasis significantly higher percutaneous transhepatic biliary drainage patients endoscopic biliary drainage patients p 005 recurrence rates sites similar 2 groups p 413 conclusion percutaneous transhepatic biliary drainage increases incidence seeding metastasis shortens postoperative survival patients perihilar cholangiocarcinoma endoscopic biliary drainage recommended optimal method preoperative biliary drainage pubmed","probabilities":0.9799733,"Title":"Verification of the oncologic inferiority of percutaneous biliary drainage to endoscopic drainage: A propensity score matching analysis of resectable perihilar cholangiocarcinoma","Abstract":"BACKGROUND: Percutaneous transhepatic biliary drainage is an established biliary drainage method but is associated with a potential risk of seeding metastasis. The aim of this retrospective study was to evaluate whether percutaneous transhepatic biliary drainage really increases seeding metastasis and worsens the postoperative survival in patients with resectable perihilar cholangiocarcinoma. METHODS: Patients who underwent resection for perihilar cholangiocarcinoma after percutaneous transhepatic biliary drainage or endoscopic biliary drainage were retrospectively reviewed. Seeding metastasis was defined as peritoneal/pleural dissemination and percutaneous transhepatic biliary drainage sinus tract recurrence. Univariate and multivariate analyses followed by propensity score matching were performed to adjust the data for the baseline characteristics of the percutaneous transhepatic biliary drainage and endoscopic biliary drainage patients. RESULTS: Of 320 resected patients, 168 underwent percutaneous transhepatic biliary drainage and the remaining 152 received endoscopic biliary drainage before operation. The survival of the percutaneous transhepatic biliary drainage patients was significantly lower than that of the endoscopic biliary drainage patients (37.0% vs 44.3% at 5 years, P = .019). Multivariate analyses showed that percutaneous transhepatic biliary drainage was an independent predictor of poor survival (P = .011) and a risk factor for seeding metastasis (P = .005). After propensity score matching (71 patients in each group), the survival of the percutaneous transhepatic biliary drainage patients was significantly worse than that of the endoscopic biliary drainage patients (P = .018). The estimated cumulative recurrence rate of seeding metastasis was significantly higher in the percutaneous transhepatic biliary drainage patients than in the endoscopic biliary drainage patients (P = .005), while the recurrence rates at other sites were similar between the 2 groups (P = .413). CONCLUSION: Percutaneous transhepatic biliary drainage increases the incidence of seeding metastasis and shortens the postoperative survival in patients with perihilar cholangiocarcinoma. Endoscopic biliary drainage is recommended as the optimal method for preoperative biliary drainage.","Source":"PubMed","category":"HUMAN","training_data":"Verification of the oncologic inferiority of percutaneous biliary drainage to endoscopic drainage: A propensity score matching analysis of resectable perihilar cholangiocarcinoma BACKGROUND: Percutaneous transhepatic biliary drainage is an established biliary drainage method but is associated with a potential risk of seeding metastasis. The aim of this retrospective study was to evaluate whether percutaneous transhepatic biliary drainage really increases seeding metastasis and worsens the postoperative survival in patients with resectable perihilar cholangiocarcinoma. METHODS: Patients who underwent resection for perihilar cholangiocarcinoma after percutaneous transhepatic biliary drainage or endoscopic biliary drainage were retrospectively reviewed. Seeding metastasis was defined as peritoneal/pleural dissemination and percutaneous transhepatic biliary drainage sinus tract recurrence. Univariate and multivariate analyses followed by propensity score matching were performed to adjust the data for the baseline characteristics of the percutaneous transhepatic biliary drainage and endoscopic biliary drainage patients. RESULTS: Of 320 resected patients, 168 underwent percutaneous transhepatic biliary drainage and the remaining 152 received endoscopic biliary drainage before operation. The survival of the percutaneous transhepatic biliary drainage patients was significantly lower than that of the endoscopic biliary drainage patients (37.0% vs 44.3% at 5 years, P = .019). Multivariate analyses showed that percutaneous transhepatic biliary drainage was an independent predictor of poor survival (P = .011) and a risk factor for seeding metastasis (P = .005). After propensity score matching (71 patients in each group), the survival of the percutaneous transhepatic biliary drainage patients was significantly worse than that of the endoscopic biliary drainage patients (P = .018). The estimated cumulative recurrence rate of seeding metastasis was significantly higher in the percutaneous transhepatic biliary drainage patients than in the endoscopic biliary drainage patients (P = .005), while the recurrence rates at other sites were similar between the 2 groups (P = .413). CONCLUSION: Percutaneous transhepatic biliary drainage increases the incidence of seeding metastasis and shortens the postoperative survival in patients with perihilar cholangiocarcinoma. Endoscopic biliary drainage is recommended as the optimal method for preoperative biliary drainage. PubMed","prediction_labels":"HUMAN"},{"cleaned":"targeting angiogenesis biliary tract cancers open option biliary tract cancers btcs characterized bad prognosis armamentarium drugs treatment poor although inflammatory status biliary tract represents first step cancerogenesis microenvironment also plays key role pathogenesis btcs promoting tumor angiogenesis invasion metastasis several molecules vascular endothelial growth factor vegf fibroblast growth factor fgf involved angiogenesis process expression tumor samples explored prognostic marker cholangiocarcinoma gallbladder cancer recent studies evaluated genomic landscape btcs evidenced aberrations several genes enrolled pro angiogenic signaling fgf receptor 2 fgfr 2 characteristic btcs new drugs targeting signaling pathways involved angiogenesis tested preclinical studies vitro vivo promising results moreover several clinical studies tested monoclonal antibodies vegf tyrosine kinase inhibitors targeting vegf mek erk pathways herein evaluate pathogenic mechanisms btcs focused angiogenesis preclinical clinical data available regarding use new anti angiogenic drugs malignancies pubmed","probabilities":0.9799733,"Title":"Targeting Angiogenesis in Biliary Tract Cancers: An Open Option","Abstract":"Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies.","Source":"PubMed","category":"HUMAN","training_data":"Targeting Angiogenesis in Biliary Tract Cancers: An Open Option Biliary tract cancers (BTCs) are characterized by a bad prognosis and the armamentarium of drugs for their treatment is very poor. Although the inflammatory status of biliary tract represents the first step in the cancerogenesis, the microenvironment also plays a key role in the pathogenesis of BTCs, promoting tumor angiogenesis, invasion and metastasis. Several molecules, such as vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF), are involved in the angiogenesis process and their expression on tumor samples has been explored as prognostic marker in both cholangiocarcinoma and gallbladder cancer. Recent studies evaluated the genomic landscape of BTCs and evidenced that aberrations in several genes enrolled in the pro-angiogenic signaling, such as FGF receptor-2 (FGFR-2), are characteristic of BTCs. New drugs targeting the signaling pathways involved in angiogenesis have been tested in preclinical studies both in vitro and in vivo with promising results. Moreover, several clinical studies tested monoclonal antibodies against VEGF and tyrosine kinase inhibitors targeting the VEGF and the MEK/ERK pathways. Herein, we evaluate both the pathogenic mechanisms of BTCs focused on angiogenesis and the preclinical and clinical data available regarding the use of new anti-angiogenic drugs in these malignancies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pancreatic periampullary biliary cancer liver metastases consider resection selected cases aim analyse safety efficacy curative intent surgery biliary pancreatic cancer methods extensive literature review performed using medline google scholar embase identify articles regarding hepato pancreatoduodenectomy resection liver metastasis patients pancreatic biliary tract periampullary gallbladder cancers results total 19 studies identified reviewed major hepatectomy undertaken 391 patients median overall survival pancreatic cancer ranged 5 36 mo biliary tract gallbladder cancer 8 38 mo 30 d mortality rate 1 9 overall survival significantly better patients good response neoadjuvant chemotherapy underwent metachronous liver resection intestinal type tumours conclusion resection liver metastases pancreatic biliary cancers may provide survival benefit without compromising safety quality life select group patients data may utilised formulate selection criteria may allow future investigation resection era effective systemic therapy stn","probabilities":0.9799733,"Title":"Pancreatic Periampullary And Biliary Cancer With Liver Metastases: Should We Consider Resection In Selected Cases?","Abstract":"Aim: To analyse the safety and efficacy of curative intent surgery in biliary and pancreatic cancer. \r\n\r\n Methods: An extensive literature review was performed using MEDLINE, Google Scholar and EMBASE to identify articles regarding hepato-pancreatoduodenectomy or resection of liver metastasis in patients with pancreatic, biliary tract, periampullary and gallbladder cancers. \r\n\r\n Results: A total of 19 studies were identified and reviewed. Major hepatectomy was undertaken in 391 patients. The median overall survival for pancreatic cancer ranged from 5-36 mo and for biliary tract/gallbladder cancer, it was 8-38 mo. The 30 d mortality rate was only 1%-9%. Overall Survival was significantly better for patients, who had good response to neoadjuvant chemotherapy, underwent metachronous liver resection and who had intestinal type tumours. \r\n\r\n Conclusion: Resection of liver metastases in pancreatic and biliary cancers may provide survival benefit without compromising safety and quality of life in a very select group of patients. These data may be utilised to formulate selection criteria that may allow future investigation of resection in the era of more effective systemic therapy.","Source":"STN","category":"HUMAN","training_data":"Pancreatic Periampullary And Biliary Cancer With Liver Metastases: Should We Consider Resection In Selected Cases? Aim: To analyse the safety and efficacy of curative intent surgery in biliary and pancreatic cancer. \r\n\r\n Methods: An extensive literature review was performed using MEDLINE, Google Scholar and EMBASE to identify articles regarding hepato-pancreatoduodenectomy or resection of liver metastasis in patients with pancreatic, biliary tract, periampullary and gallbladder cancers. \r\n\r\n Results: A total of 19 studies were identified and reviewed. Major hepatectomy was undertaken in 391 patients. The median overall survival for pancreatic cancer ranged from 5-36 mo and for biliary tract/gallbladder cancer, it was 8-38 mo. The 30 d mortality rate was only 1%-9%. Overall Survival was significantly better for patients, who had good response to neoadjuvant chemotherapy, underwent metachronous liver resection and who had intestinal type tumours. \r\n\r\n Conclusion: Resection of liver metastases in pancreatic and biliary cancers may provide survival benefit without compromising safety and quality of life in a very select group of patients. These data may be utilised to formulate selection criteria that may allow future investigation of resection in the era of more effective systemic therapy. STN","prediction_labels":"HUMAN"},{"cleaned":"survival rates higher married patients biliary tract cancer population based study marital status identified prognostic factor multiple malignancies study assessed prognostic value marital status 24 035 patients surveillance epidemiology end results database diagnosed biliary tract cancer btc 2004 2014 widowed patients likely women elderly 60 years gallbladder cancer localized seer stage disease patients marital status identified independent prognostic factor univariate multivariate analyses cause specific survival css rates higher married patients unmarried patients addition css rates higher ampulla vater cancer patients gallbladder cancer cholangiocarcinoma patients analysis revealed css rates lowest widowed patients tnm stage tumor sites results suggest marital status prognostic factor clinical outcomes patients btc widowed patients greater risk cancer specific mortality google scholar","probabilities":0.9799733,"Title":"Survival Rates Are Higher In Married Patients With Biliary Tract Cancer: A Population-Based Study","Abstract":"Marital status has been identified as a prognostic factor in multiple malignancies. In this study, we assessed the prognostic value of marital status in 24,035 patients from the Surveillance, Epidemiology, and End Results database diagnosed with biliary tract cancer (BTC) between 2004 and 2014. Widowed patients were more likely to be women, elderly (> 60 years), have gallbladder cancer, and have localized SEER Stage disease than all other patients. Marital status was identified as an independent prognostic factor in both univariate and multivariate analyses, and cause-specific survival (CSS) rates were higher in married patients than unmarried patients. In addition, CSS rates were higher in ampulla of Vater cancer patients than in gallbladder cancer or cholangiocarcinoma patients. Further analysis revealed that CSS rates were lowest in widowed patients at each TNM stage and for all tumor sites. These results suggest marital status is a prognostic factor for clinical outcomes in patients with BTC, and widowed patients are at greater risk of cancer-specific mortality.","Source":"Google Scholar","category":"HUMAN","training_data":"Survival Rates Are Higher In Married Patients With Biliary Tract Cancer: A Population-Based Study Marital status has been identified as a prognostic factor in multiple malignancies. In this study, we assessed the prognostic value of marital status in 24,035 patients from the Surveillance, Epidemiology, and End Results database diagnosed with biliary tract cancer (BTC) between 2004 and 2014. Widowed patients were more likely to be women, elderly (> 60 years), have gallbladder cancer, and have localized SEER Stage disease than all other patients. Marital status was identified as an independent prognostic factor in both univariate and multivariate analyses, and cause-specific survival (CSS) rates were higher in married patients than unmarried patients. In addition, CSS rates were higher in ampulla of Vater cancer patients than in gallbladder cancer or cholangiocarcinoma patients. Further analysis revealed that CSS rates were lowest in widowed patients at each TNM stage and for all tumor sites. These results suggest marital status is a prognostic factor for clinical outcomes in patients with BTC, and widowed patients are at greater risk of cancer-specific mortality.\n Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic value lymph nodes count survival patients distal cholangiocarcinomas aim evaluate prognostic value number retrieved lymph nodes lns prognostic factors patients distal cholangiocarcinomas determine optimal retrieved lns cut number methods surveillance epidemiology end results database used screen patients distal cholangiocarcinoma patients different numbers retrieved lns divided three groups x tile program x tile yale university useful tool outcome based cut point optimization kaplan meier method cox regression analysis utilized survival analysis results total 449 patients distal cholangiocarcinoma met inclusion criteria kaplan meier survival analysis patients n1 patients revealed significant differences among patients different retrieved ln counts terms overall cancer specific survival patients node negative distal cholangiocarcinoma patients four nine retrieved lns significantly better overall p 0 026 cancer specific survival p 0 039 others subsequent multivariate analysis number retrieved lns evaluated independently associated survival additionally patients four nine retrieved lns significantly lower overall mortality risk hazard ratio hr 0 39 95 confidence interval ci 0 20 0 74 cancer cause specific mortality risk hr 0 32 95 ci 0 15 0 66 patients additionally stratified survival analyses showed persistently better overall cancer specific survival retrieving four nine lns patients stage tumor tumor 20 50 mm diameter poorly differentiated undifferentiated tumor patients 70 years old conclusion number retrieved lns important independent prognostic factor patients node negative distal cholangiocarcinoma additionally patients four nine retrieved lns better overall cancer specific survival rates others reason mechanism unclear conclusion validated future studies pubmed","probabilities":0.9799733,"Title":"Prognostic value of lymph nodes count on survival of patients with distal cholangiocarcinomas","Abstract":"AIM: To evaluate the prognostic value of the number of retrieved lymph nodes (LNs) and other prognostic factors for patients with distal cholangiocarcinomas, and to determine the optimal retrieved LNs cut-off number. METHODS: The Surveillance, Epidemiology and End Results database was used to screen for patients with distal cholangiocarcinoma. Patients with different numbers of retrieved LNs were divided into three groups by the X-tile program. X-tile from Yale University is a useful tool for outcome-based cut-point optimization. The Kaplan-Meier method and Cox regression analysis were utilized for survival analysis. RESULTS: A total of 449 patients with distal cholangiocarcinoma met the inclusion criteria. The Kaplan-Meier survival analysis for all patients and for N1 patients revealed no significant differences among patients with different retrieved LN counts in terms of overall and cancer-specific survival. In patients with node-negative distal cholangiocarcinoma, patients with four to nine retrieved LNs had a significantly better overall (P = 0.026) and cancer-specific survival (P = 0.039) than others. In the subsequent multivariate analysis, the number of retrieved LNs was evaluated to be independently associated with survival. Additionally, patients with four to nine retrieved LNs had a significantly lower overall mortality risk [hazard ratio (HR) = 0.39; 95% confidence interval (CI): 0.20-0.74] and cancer cause-specific mortality risk (HR = 0.32; 95%CI: 0.15-0.66) than other patients. Additionally, stratified survival analyses showed persistently better overall and cancer-specific survival when retrieving four to nine LNs in patients with any T stage of tumor, a tumor between 20 and 50 mm in diameter, or a poorly differentiated or undifferentiated tumor, and in patients who were ≤ 70-years-old. CONCLUSION: The number of retrieved LNs was an important independent prognostic factor for patients with node-negative distal cholangiocarcinoma. Additionally, patients with four to nine retrieved LNs had better overall and cancer-specific survival rates than others, but the reason and mechanism were unclear. This conclusion should be validated in future studies.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic value of lymph nodes count on survival of patients with distal cholangiocarcinomas AIM: To evaluate the prognostic value of the number of retrieved lymph nodes (LNs) and other prognostic factors for patients with distal cholangiocarcinomas, and to determine the optimal retrieved LNs cut-off number. METHODS: The Surveillance, Epidemiology and End Results database was used to screen for patients with distal cholangiocarcinoma. Patients with different numbers of retrieved LNs were divided into three groups by the X-tile program. X-tile from Yale University is a useful tool for outcome-based cut-point optimization. The Kaplan-Meier method and Cox regression analysis were utilized for survival analysis. RESULTS: A total of 449 patients with distal cholangiocarcinoma met the inclusion criteria. The Kaplan-Meier survival analysis for all patients and for N1 patients revealed no significant differences among patients with different retrieved LN counts in terms of overall and cancer-specific survival. In patients with node-negative distal cholangiocarcinoma, patients with four to nine retrieved LNs had a significantly better overall (P = 0.026) and cancer-specific survival (P = 0.039) than others. In the subsequent multivariate analysis, the number of retrieved LNs was evaluated to be independently associated with survival. Additionally, patients with four to nine retrieved LNs had a significantly lower overall mortality risk [hazard ratio (HR) = 0.39; 95% confidence interval (CI): 0.20-0.74] and cancer cause-specific mortality risk (HR = 0.32; 95%CI: 0.15-0.66) than other patients. Additionally, stratified survival analyses showed persistently better overall and cancer-specific survival when retrieving four to nine LNs in patients with any T stage of tumor, a tumor between 20 and 50 mm in diameter, or a poorly differentiated or undifferentiated tumor, and in patients who were ≤ 70-years-old. CONCLUSION: The number of retrieved LNs was an important independent prognostic factor for patients with node-negative distal cholangiocarcinoma. Additionally, patients with four to nine retrieved LNs had better overall and cancer-specific survival rates than others, but the reason and mechanism were unclear. This conclusion should be validated in future studies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact age diagnosis disease progression patients primary sclerosing cholangitis background median age diagnosis primary sclerosing cholangitis psc 30 40 years objective aimed analyse disease progression liver dependent survival patients diagnosed psc 50 years age methods patients psc analysed regard age diagnosis patients first diagnosis psc age 50 years considered late onset group results total 32 215 14 9 patients diagnosed psc 50 years age proportion females significantly higher among patients late onset psc 48 4 vs 27 3 p 0 02 patients later diagnosis required dilatation therapy often due dominant stenosis 84 2 vs 53 1 p 0 01 suffered recurrent cholangitis often 48 3 vs 21 0 p 0 003 patients late onset psc reduced transplantation free survival 10 5 0 6 years vs 20 8 1 7 years p 0 0001 progredient liver failure cholangiocarcinoma leading causes death conclusions patients later age diagnosis psc displayed different clinical phenotype different sex ratio immune status increased risk progressive liver failure biliary malignancies google scholar","probabilities":0.9799733,"Title":"Impact Of Age At Diagnosis On Disease Progression In Patients With Primary Sclerosing Cholangitis","Abstract":"Background\nThe median age of diagnosis of primary sclerosing cholangitis (PSC) is ∼30–40 years.\n\nObjective\nWe aimed to analyse disease progression and liver-dependent survival in patients diagnosed with PSC after 50 years of age.\n\nMethods\nPatients with PSC were analysed with regard to their age at diagnosis. Patients with a first diagnosis of PSC after the age of 50 years were considered as the late-onset group.\n\nResults\nA total of 32/215 (14.9%) patients were diagnosed with PSC after 50 years of age. The proportion of females was significantly higher among patients with late-onset PSC (48.4 vs. 27.3%; p = 0.02). Patients with later diagnosis required dilatation therapy more often due to dominant stenosis (84.2 vs. 53.1%; p = 0.01) and suffered from recurrent cholangitis more often (48.3 vs. 21.0%; p = 0.003). Patients with late-onset PSC had reduced transplantation-free survival (10.5 ± 0.6 years vs. 20.8 ± 1.7 years, p < 0.0001), with progredient liver failure and cholangiocarcinoma as the leading causes of death.\n\nConclusions\nPatients with later age at diagnosis of PSC displayed a different clinical phenotype with a different sex ratio, immune status and an increased risk for progressive liver failure and biliary malignancies.","Source":"Google Scholar","category":"HUMAN","training_data":"Impact Of Age At Diagnosis On Disease Progression In Patients With Primary Sclerosing Cholangitis Background\nThe median age of diagnosis of primary sclerosing cholangitis (PSC) is ∼30–40 years.\n\nObjective\nWe aimed to analyse disease progression and liver-dependent survival in patients diagnosed with PSC after 50 years of age.\n\nMethods\nPatients with PSC were analysed with regard to their age at diagnosis. Patients with a first diagnosis of PSC after the age of 50 years were considered as the late-onset group.\n\nResults\nA total of 32/215 (14.9%) patients were diagnosed with PSC after 50 years of age. The proportion of females was significantly higher among patients with late-onset PSC (48.4 vs. 27.3%; p = 0.02). Patients with later diagnosis required dilatation therapy more often due to dominant stenosis (84.2 vs. 53.1%; p = 0.01) and suffered from recurrent cholangitis more often (48.3 vs. 21.0%; p = 0.003). Patients with late-onset PSC had reduced transplantation-free survival (10.5 ± 0.6 years vs. 20.8 ± 1.7 years, p < 0.0001), with progredient liver failure and cholangiocarcinoma as the leading causes of death.\n\nConclusions\nPatients with later age at diagnosis of PSC displayed a different clinical phenotype with a different sex ratio, immune status and an increased risk for progressive liver failure and biliary malignancies. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"epidemiology prevalence national trends combined hepatocellular carcinoma cholangiocarcinoma chcc cca hospitalized us patients 2002 2014 background chcc cca represents rare type primary liver cancer first identified 1949 aim study evaluate epidemiology clinical outcomes national trends chcc cca hospitalized us patients using nationwide inpatient sample database nis methods nis database inquired identify patients hcc 2002 2014 using icd9 cm codes patients hcc classified two groups one group cholangiocarcinoma cca group without cca spss version 25 used statistical analysis results identified 525 699 patients hcc 2002 2014 2 158 patients 0 4 cca chcc cca group 87 8 patients 50 years old 58 1 male 63 7 caucasian 10 african american mortality patients hospitalized chcc cca 8 5 compared 11 1 patients hcc 0 74 95 ci 0 64 0 86 p 0 0001 mortality chcc cca patients decreased 19 1 2002 7 9 2014 median length stay los patients chcc cca 6 days compared 4 days patients hcc p 0 0001 median los patients chcc cca unchanged 2002 2014 median hospitalization cost charge chcc cca patients 41 012 usd compared 28 371 usd hcc patients chcc cca group increased 17 243 usd 2002 37 234 usd 2014 0 9 patients chcc cca underwent liver transplantation compared 3 5 hcc patients 0 26 95 ci 0 17 0 41 p 0 0001 conclusions prevalence chcc cca 0 4 patients hcc study period chcc cca unexpectedly associated less mortality possibly limitations comparison due smaller number patients compared hcc alone chcc cca also associated lower rates liver transplantation prolonged los higher hospitalization cost charge compared hcc patients period mortality decreased chcc cca patients cost charge increased prevalence los unchanged studies needed evaluate understand chcc cca separate entity google scholar","probabilities":0.9799733,"Title":"Epidemiology Prevalence And National Trends Of Combined Hepatocellular Carcinoma-Cholangiocarcinoma (Chcc-Cca) In Hospitalized Us Patients Between 2002-2014","Abstract":"Background: cHCC-CCA represents a rare type of primary liver cancer that was first identified in 1949. The aim of this study is to evaluate epidemiology, clinical outcomes and national trends of cHCC-CCA in hospitalized US patients using the Nationwide Inpatient Sample database (NIS). Methods: NIS database was inquired to identify patients with HCC between 2002 and 2014 using ICD9-CM codes. Patients with HCC were classified into two groups, one group with cholangiocarcinoma (CCA) and the other group without CCA. SPSS version 25 was used for statistical analysis. Results: We identified 525,699 patients with HCC between 2002-2014. Of them, 2,158 patients (0.4%) had CCA. In the cHCC-CCA group, 87.8% of the patients were above 50 years old, 58.1% were male, 63.7% were Caucasian, and 10% were African American. Mortality in patients hospitalized with cHCC-CCA was 8.5% compared to 11.1% in patients with HCC (OR 0.74, 95% CI 0.64-0.86, P < 0.0001). Mortality in cHCC-CCA patients decreased from 19.1% in 2002 to 7.9% in 2014. The median length of stay (LOS) in patients with cHCC-CCA was 6 days compared to 4 days in patients with HCC (P < 0.0001). Median LOS for patients with cHCC-CCA was unchanged between 2002 and 2014. The median hospitalization cost of charge in cHCC-CCA patients was 41,012 USD compared to 28,371 USD in HCC patients. In the cHCC-CCA group, it increased from 17,243 USD in 2002 to 37,234 USD in 2014. Only 0.9% of patients with cHCC-CCA underwent liver transplantation compared to 3.5% of HCC patients (OR 0.26, 95% CI (0.17-0.41), P < 0.0001). Conclusions: Prevalence of cHCC-CCA was 0.4% of patients with HCC during the study period. cHCC-CCA was unexpectedly associated with less mortality; possibly because of limitations in comparison due to the smaller number of patients compared to HCC alone. cHCC-CCA was also associated with lower rates of liver transplantation but more prolonged LOS and higher hospitalization cost of charge compared to HCC patients. In the same period, mortality decreased in cHCC-CCA patients and cost of charge increased while prevalence and LOS were unchanged. Further studies are needed to evaluate and understand cHCC-CCA as a separate entity.","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology Prevalence And National Trends Of Combined Hepatocellular Carcinoma-Cholangiocarcinoma (Chcc-Cca) In Hospitalized Us Patients Between 2002-2014 Background: cHCC-CCA represents a rare type of primary liver cancer that was first identified in 1949. The aim of this study is to evaluate epidemiology, clinical outcomes and national trends of cHCC-CCA in hospitalized US patients using the Nationwide Inpatient Sample database (NIS). Methods: NIS database was inquired to identify patients with HCC between 2002 and 2014 using ICD9-CM codes. Patients with HCC were classified into two groups, one group with cholangiocarcinoma (CCA) and the other group without CCA. SPSS version 25 was used for statistical analysis. Results: We identified 525,699 patients with HCC between 2002-2014. Of them, 2,158 patients (0.4%) had CCA. In the cHCC-CCA group, 87.8% of the patients were above 50 years old, 58.1% were male, 63.7% were Caucasian, and 10% were African American. Mortality in patients hospitalized with cHCC-CCA was 8.5% compared to 11.1% in patients with HCC (OR 0.74, 95% CI 0.64-0.86, P < 0.0001). Mortality in cHCC-CCA patients decreased from 19.1% in 2002 to 7.9% in 2014. The median length of stay (LOS) in patients with cHCC-CCA was 6 days compared to 4 days in patients with HCC (P < 0.0001). Median LOS for patients with cHCC-CCA was unchanged between 2002 and 2014. The median hospitalization cost of charge in cHCC-CCA patients was 41,012 USD compared to 28,371 USD in HCC patients. In the cHCC-CCA group, it increased from 17,243 USD in 2002 to 37,234 USD in 2014. Only 0.9% of patients with cHCC-CCA underwent liver transplantation compared to 3.5% of HCC patients (OR 0.26, 95% CI (0.17-0.41), P < 0.0001). Conclusions: Prevalence of cHCC-CCA was 0.4% of patients with HCC during the study period. cHCC-CCA was unexpectedly associated with less mortality; possibly because of limitations in comparison due to the smaller number of patients compared to HCC alone. cHCC-CCA was also associated with lower rates of liver transplantation but more prolonged LOS and higher hospitalization cost of charge compared to HCC patients. In the same period, mortality decreased in cHCC-CCA patients and cost of charge increased while prevalence and LOS were unchanged. Further studies are needed to evaluate and understand cHCC-CCA as a separate entity. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prospective proteomic based study identifying potential biomarkers diagnosis cholangiocarcinoma background cholangiocarcinoma cca becoming common fatal hepatic tumor early detection cca hampered absence sufficiently accurate noninvasive diagnostic test proteomic analysis powerful tool identify potential biomarkers cancer aims study aims identify new protein markers specific cca using proteomic approaches evaluate performance s100 calcium binding protein a9 s100a9 chaperonin containing tcr1 subunit 3 cct diagnostic markers screening test cca methods two dimensional differential gel electrophoresis 2 d dige coupled matrix assisted laser desorption ionization time flight maldi tof mass spectrometry used analyze screen biomarker candidates proteomes five human cca samples five healthy control samples subsequently two potential biomarkers s100a9 cct chosen validation analysis immunohistochemical methods using cca tissue microarrays results twenty protein spots significantly elevated five protein spots downregulated patients p 0 05 positive rate significantly higher patients cca 48 35 compared normal liver control group 5 10 p 0 001 hepatocellular carcinoma group 15 20 p 0 001 cirrhosis group 12 16 p 0 001 greater proportion patients cca positive cct 72 18 compared normal liver control group 43 22 p 0 001 hepatocellular carcinoma group 45 20 p 0 001 cirrhosis group 39 25 p 0 001 conclusions combined comparative proteomic analysis using 2 d dige maldi tof effective method identifying differentially expressed proteins cca tissues expression s100a9 cct showed promise novel diagnostic markers cca stn","probabilities":1.0,"Title":"A Prospective Proteomic-Based Study For Identifying Potential Biomarkers For The Diagnosis Of Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinoma (CCA) is becoming a common fatal hepatic tumor. Early detection of CCA is hampered by the absence of a sufficiently accurate and noninvasive diagnostic test. Proteomic analysis would be a powerful tool to identify potential biomarkers of this cancer. \r\n\r\n Aims: This study aims to identify new protein markers that are specific for CCA using proteomic approaches and to evaluate the performance of S100 calcium-binding protein A9 (S100A9) and chaperonin-containing TCR1, subunit 3 (CCTγ) as diagnostic markers for screening test of CCA. \r\n\r\n Methods: Two-dimensional differential gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were used to analyze and screen biomarker candidates in the proteomes of five human CCA samples and five healthy control samples. Subsequently, two potential biomarkers, S100A9 and CCTγ, were chosen for validation and analysis by immunohistochemical methods using CCA tissue microarrays. \r\n\r\n Results: Twenty protein spots were significantly elevated and five protein spots were downregulated in all patients (p < 0.05). The positive rate was significantly higher in patients with CCA (48 ± 35%) compared with the normal liver control group (5 ± 10%, p < 0.001), the hepatocellular carcinoma group (15 ± 20%, p < 0.001), and the cirrhosis group (12 ± 16%, p < 0.001). A greater proportion of patients with CCA were positive for CCTγ (72 ± 18%) compared with the normal liver control group (43 ± 22%, p < 0.001), the hepatocellular carcinoma group (45 ± 20%, p < 0.001), and the cirrhosis group (39 ± 25%, p < 0.001). \r\n\r\n Conclusions: Combined comparative proteomic analysis using 2-D DIGE and MALDI-TOF is an effective method for identifying differentially expressed proteins in CCA tissues. The expression of S100A9 and CCTγ showed promise as novel diagnostic markers for CCA.","Source":"STN","category":"ANIMAL","training_data":"A Prospective Proteomic-Based Study For Identifying Potential Biomarkers For The Diagnosis Of Cholangiocarcinoma Background: Cholangiocarcinoma (CCA) is becoming a common fatal hepatic tumor. Early detection of CCA is hampered by the absence of a sufficiently accurate and noninvasive diagnostic test. Proteomic analysis would be a powerful tool to identify potential biomarkers of this cancer. \r\n\r\n Aims: This study aims to identify new protein markers that are specific for CCA using proteomic approaches and to evaluate the performance of S100 calcium-binding protein A9 (S100A9) and chaperonin-containing TCR1, subunit 3 (CCTγ) as diagnostic markers for screening test of CCA. \r\n\r\n Methods: Two-dimensional differential gel electrophoresis (2-D DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry were used to analyze and screen biomarker candidates in the proteomes of five human CCA samples and five healthy control samples. Subsequently, two potential biomarkers, S100A9 and CCTγ, were chosen for validation and analysis by immunohistochemical methods using CCA tissue microarrays. \r\n\r\n Results: Twenty protein spots were significantly elevated and five protein spots were downregulated in all patients (p < 0.05). The positive rate was significantly higher in patients with CCA (48 ± 35%) compared with the normal liver control group (5 ± 10%, p < 0.001), the hepatocellular carcinoma group (15 ± 20%, p < 0.001), and the cirrhosis group (12 ± 16%, p < 0.001). A greater proportion of patients with CCA were positive for CCTγ (72 ± 18%) compared with the normal liver control group (43 ± 22%, p < 0.001), the hepatocellular carcinoma group (45 ± 20%, p < 0.001), and the cirrhosis group (39 ± 25%, p < 0.001). \r\n\r\n Conclusions: Combined comparative proteomic analysis using 2-D DIGE and MALDI-TOF is an effective method for identifying differentially expressed proteins in CCA tissues. The expression of S100A9 and CCTγ showed promise as novel diagnostic markers for CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"18f fdg pet independently predicts survival patients cholangiocellular carcinoma treated 90y microspheres purpose 90 y radioembolization emerged valuable therapy intrahepatic cholangiocellular carcinomas icc aimed evaluate prognostic power fdg pet ct pretherapeutic scintigraphy 99m tc labelled macroagglutinated albumin maa index tumour vascularization methods study group comprised 26 consecutive patients suffering nonresectable icc treatment radioembolization patients underwent mri liver well maa scintigraphy followed immediately spect ct quantify liver lung shunt fraction using image fusion regions interest drawn around tumours entire liver tumour liver quotient calculated addition fdg pet ct performed baseline 3 months radioembolization percentage changes peak suv max mean suv mean fdg uptake metabolic tumour volume vol 2sd relative baseline calculated treatment response 3 months also assessed using contrast enhanced mri ct basis standard criteria results 23 patients follow mri available 5 22 showed partial response 15 65 stable disease 3 13 progressive disease change fdg values significantly predicted survival kaplan meier analysis radioembolization vol 2sd responders median survival 97 weeks versus 30 weeks nonresponders p 0 02 whereas suv max suv mean responders median survival 114 weeks responder versus 19 weeks nonresponder 69 weeks patients stable disease p 0 05 pretherapeutic maa scintigraphy mri predict survival presence extrahepatic metastases prior therapies vol 2sd significantly associated survival univariate analysis hazard ratio 0 25 p 0 04 multivariate analysis hazard ratio 0 20 p 0 04 conclusion fdg pet ct able predict patient outcome radioembolization treatment change metabolically active tumour volume 3 months best independent predictor high tumour vascularization indicated maa scintigraphy prerequisite successful radioembolization even associated tendency towards shorter survival pubmed","probabilities":0.9799733,"Title":"18F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with 90Y microspheres","Abstract":"PURPOSE: (90)Y radioembolization has emerged as a valuable therapy for intrahepatic cholangiocellular carcinomas (ICC). We aimed to evaluate the prognostic power of FDG PET/CT and that of pretherapeutic scintigraphy with (99m)Tc-labelled macroagglutinated albumin (MAA), an index of tumour vascularization. METHODS: The study group comprised 26 consecutive patients suffering from nonresectable ICC. Before treatment with radioembolization, all patients underwent MRI of the liver, as well as MAA scintigraphy, which was followed immediately by SPECT(/CT) to quantify the liver-lung shunt fraction. Using image fusion, regions of interest were drawn around the tumours and the entire liver, and the tumour-to-liver quotient was calculated. In addition, FDG PET/CT was performed at baseline and 3 months after radioembolization, and the percentage changes in peak (ΔSUV(max)) and mean (ΔSUV(mean)) FDG uptake and in metabolic tumour volume (ΔVol(2SD)) relative to baseline were calculated. Treatment response at 3 months was also assessed using contrast-enhanced MRI and CT on the basis of standard criteria. RESULTS: Of 23 patients in whom follow-up MRI was available, 5 (22%) showed a partial response, 15 (65%) stable disease and 3 (13%) progressive disease. The change in all FDG values significantly predicted survival by Kaplan-Meier analysis after radioembolization; ΔVol(2SD) responders had a median survival of 97 weeks versus 30 weeks in nonresponders (P = 0.02), whereas ΔSUV(max) and ΔSUV(mean) responders had a median survival of 114 weeks (responder) versus 19 weeks (nonresponder) and 69 weeks in patients with stable disease (P < 0.05). Pretherapeutic MAA scintigraphy or MRI did not predict survival, nor did the presence of extrahepatic metastases, or prior therapies. Only ΔVol(2SD) was significantly associated with survival by univariate analysis (hazard ratio 0.25; P = 0.04) and multivariate analysis (hazard ratio 0.20, P = 0.04). CONCLUSION: FDG PET/CT was able to predict patient outcome after radioembolization treatment, with the change in metabolically active tumour volume at 3 months being the best independent predictor. High tumour vascularization, as indicated by MAA scintigraphy, was not a prerequisite for successful radioembolization and was even associated with a tendency towards shorter survival.","Source":"PubMed","category":"HUMAN","training_data":"18F-FDG PET independently predicts survival in patients with cholangiocellular carcinoma treated with 90Y microspheres PURPOSE: (90)Y radioembolization has emerged as a valuable therapy for intrahepatic cholangiocellular carcinomas (ICC). We aimed to evaluate the prognostic power of FDG PET/CT and that of pretherapeutic scintigraphy with (99m)Tc-labelled macroagglutinated albumin (MAA), an index of tumour vascularization. METHODS: The study group comprised 26 consecutive patients suffering from nonresectable ICC. Before treatment with radioembolization, all patients underwent MRI of the liver, as well as MAA scintigraphy, which was followed immediately by SPECT(/CT) to quantify the liver-lung shunt fraction. Using image fusion, regions of interest were drawn around the tumours and the entire liver, and the tumour-to-liver quotient was calculated. In addition, FDG PET/CT was performed at baseline and 3 months after radioembolization, and the percentage changes in peak (ΔSUV(max)) and mean (ΔSUV(mean)) FDG uptake and in metabolic tumour volume (ΔVol(2SD)) relative to baseline were calculated. Treatment response at 3 months was also assessed using contrast-enhanced MRI and CT on the basis of standard criteria. RESULTS: Of 23 patients in whom follow-up MRI was available, 5 (22%) showed a partial response, 15 (65%) stable disease and 3 (13%) progressive disease. The change in all FDG values significantly predicted survival by Kaplan-Meier analysis after radioembolization; ΔVol(2SD) responders had a median survival of 97 weeks versus 30 weeks in nonresponders (P = 0.02), whereas ΔSUV(max) and ΔSUV(mean) responders had a median survival of 114 weeks (responder) versus 19 weeks (nonresponder) and 69 weeks in patients with stable disease (P < 0.05). Pretherapeutic MAA scintigraphy or MRI did not predict survival, nor did the presence of extrahepatic metastases, or prior therapies. Only ΔVol(2SD) was significantly associated with survival by univariate analysis (hazard ratio 0.25; P = 0.04) and multivariate analysis (hazard ratio 0.20, P = 0.04). CONCLUSION: FDG PET/CT was able to predict patient outcome after radioembolization treatment, with the change in metabolically active tumour volume at 3 months being the best independent predictor. High tumour vascularization, as indicated by MAA scintigraphy, was not a prerequisite for successful radioembolization and was even associated with a tendency towards shorter survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effects liver cirrhosis patient condition clinical outcomes intrahepatic cholangiocarcinoma retrospective analysis 156 cases single center objective incidence intrahepatic cholangiocarcinoma icca increasing past decades liver cirrhosis independent risk factor development icca study aimed examine prognostic impact liver cirrhosis patient condition treatment icca patients methods retrospectively analyzed cases 156 patients diagnosed icca 1990 2014 center patients divided subgroups depending presence severity liver cirrhosis type treatment clinical data patient characteristics overall survival compared groups results forty seven 30 156 patients liver cirrhosis predominantly child pugh scores n 27 b n 12 median survival differed patients receiving tumor resection 34 months chemotherapy 10 months best supportive care 2 months eastern cooperative oncology group performance status score 1 predictor poor survival patients p 0 001 independent presence cirrhosis resection performed less frequently cirrhotic patients 6 vs 31 patients p 0 04 resection performed presence cirrhosis b influence survival cirrhosis b influence outcome patients receiving chemotherapy either cirrhotic patients receiving chemotherapy cancer antigen 19 9 levels 129 u ml associated significantly shorter survival 22 5 vs 3 months p 0 0003 conclusion presence liver cirrhosis icca underestimated difference survival noncirrhotic patients patients compensated cirrhosis patients general condition seems prognostic value treatment icca presence cirrhosis therefore presence cirrhosis b prevent patients good eastern cooperative oncology group performance status score receiving tumor resection chemotherapy pubmed","probabilities":0.9799733,"Title":"Effects of liver cirrhosis and patient condition on clinical outcomes in intrahepatic cholangiocarcinoma: a retrospective analysis of 156 cases in a single center","Abstract":"OBJECTIVE: The incidence of intrahepatic cholangiocarcinoma (iCCA) has been increasing over the past few decades. Liver cirrhosis is an independent risk factor for the development of iCCA. This study aimed to examine the prognostic impact of liver cirrhosis and patient condition on the treatment of iCCA. PATIENTS AND METHODS: We retrospectively analyzed the cases of 156 patients diagnosed with iCCA between 1990 and 2014 in our center. Patients were divided into subgroups depending on the presence and severity of liver cirrhosis and the type of treatment. Clinical data, patient characteristics, and overall survival were compared between these groups. RESULTS: Forty-seven (30%) of 156 patients had liver cirrhosis, predominantly with Child-Pugh scores A (n=27) and B (n=12). The median survival differed between patients receiving tumor resection (34 months), chemotherapy (10 months), and best supportive care (2 months). An Eastern Cooperative Oncology Group Performance Status score more than 1 was a predictor of poor survival in all patients (P<0.001), independent of the presence of cirrhosis. Resection could be performed less frequently in cirrhotic patients (6 vs. 31 patients; P=0.04). If resection was performed, the presence of cirrhosis A/B did not influence survival. Cirrhosis A/B did not influence the outcome in patients receiving chemotherapy either. In cirrhotic patients receiving chemotherapy, cancer antigen 19-9 levels above 129 U/ml were associated with a significantly shorter survival (22.5 vs. 3 months, P=0.0003). CONCLUSION: The presence of liver cirrhosis in iCCA has been underestimated. There was no difference in survival between noncirrhotic patients and patients with compensated cirrhosis. Patients' general condition seems to be of more prognostic value in the treatment of iCCA than the presence of cirrhosis. Therefore, the presence of cirrhosis A/B should not prevent patients with a good Eastern Cooperative Oncology Group Performance Status score from receiving tumor resection or chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Effects of liver cirrhosis and patient condition on clinical outcomes in intrahepatic cholangiocarcinoma: a retrospective analysis of 156 cases in a single center OBJECTIVE: The incidence of intrahepatic cholangiocarcinoma (iCCA) has been increasing over the past few decades. Liver cirrhosis is an independent risk factor for the development of iCCA. This study aimed to examine the prognostic impact of liver cirrhosis and patient condition on the treatment of iCCA. PATIENTS AND METHODS: We retrospectively analyzed the cases of 156 patients diagnosed with iCCA between 1990 and 2014 in our center. Patients were divided into subgroups depending on the presence and severity of liver cirrhosis and the type of treatment. Clinical data, patient characteristics, and overall survival were compared between these groups. RESULTS: Forty-seven (30%) of 156 patients had liver cirrhosis, predominantly with Child-Pugh scores A (n=27) and B (n=12). The median survival differed between patients receiving tumor resection (34 months), chemotherapy (10 months), and best supportive care (2 months). An Eastern Cooperative Oncology Group Performance Status score more than 1 was a predictor of poor survival in all patients (P<0.001), independent of the presence of cirrhosis. Resection could be performed less frequently in cirrhotic patients (6 vs. 31 patients; P=0.04). If resection was performed, the presence of cirrhosis A/B did not influence survival. Cirrhosis A/B did not influence the outcome in patients receiving chemotherapy either. In cirrhotic patients receiving chemotherapy, cancer antigen 19-9 levels above 129 U/ml were associated with a significantly shorter survival (22.5 vs. 3 months, P=0.0003). CONCLUSION: The presence of liver cirrhosis in iCCA has been underestimated. There was no difference in survival between noncirrhotic patients and patients with compensated cirrhosis. Patients' general condition seems to be of more prognostic value in the treatment of iCCA than the presence of cirrhosis. Therefore, the presence of cirrhosis A/B should not prevent patients with a good Eastern Cooperative Oncology Group Performance Status score from receiving tumor resection or chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"stromal derived factor 1 sdf 1 cxcr4 axis important role interaction human hepatic stellate cells hhsc cc cell lines backgrounds aims cholangiocarcinoma cca highly fatal early invasion widespread metastasis lack effective therapy migration invasion metastasis cca cells modulated signals received stromal cells sdf 1 cxcr4 axis emerges pivotal regulator migration survival different tumor cells aim present study characterize interaction cca cells human hepatic stellate cells hhsc focusing role sdf 1 methods intrahepatic cca cell line hucct 1 primary hhsc used study rna expression examined rtq pcr protein expression western blotting immunofluorescence microscopy immunohistochemistry also employed migration cca cells assessed using modified boyden chambers results cxcr4 clearly expressed cca cells human cca liver specimens sdf 1 hhsc conditioned medium cm promoted hucct 1 cell migration abrogated pre incubation amd3100 non peptide antagonist cxcr4 receptor addition hucct 1 cells silenced cxcr4 migrate presence sdf 1 p erk p akt implicated hucct 1 migration showed biphasic trend stimulation sdf 1 finally sdf 1 induced apoptotic rescue hucct 1 cells binding cxcr4 conclusions study demonstrates cca cells migration survival modulated crosstalk sdf 1 released hhsc hucct 1 cells bearing cxcr4 stn","probabilities":0.9467213,"Title":"Stromal-Derived Factor-1 (Sdf-1) - Cxcr4 Axis Has An Important Role On The Interaction Of Human Hepatic Stellate Cells (Hhsc) And Cc Cell Lines","Abstract":"Backgrounds & aims: Cholangiocarcinoma (CCA) is highly fatal because of early invasion, widespread metastasis, and lack of an effective therapy. Migration, invasion, and metastasis of CCA cells are modulated by signals received from stromal cells. The SDF-1-CXCR4 axis emerges as a pivotal regulator of migration and survival of different tumor cells. The aim of the present study was to characterize the interaction between CCA cells and human hepatic stellate cells (hHSC) focusing on the role of SDF-1. \r\n\r\n Methods: The intrahepatic CCA cell line HuCCT-1 and primary hHSC were used for this study. RNA expression was examined by RTQ-PCR and protein expression by Western blotting. Immunofluorescence microscopy and immunohistochemistry were also employed. Migration of CCA cells was assessed using modified Boyden chambers. \r\n\r\n Results: CXCR4 was clearly expressed in CCA cells of human CCA liver specimens. SDF-1 and hHSC conditioned medium (CM) promoted HuCCT-1 cell migration, which was abrogated by pre-incubation with AMD3100, a non-peptide antagonist of the CXCR4 receptor. In addition, HuCCT-1 cells silenced for CXCR4 did not migrate in presence of SDF-1. Both P-ERK and p-AKT were implicated in HuCCT-1 migration and showed a biphasic trend under stimulation of SDF-1. Finally, SDF-1 induced apoptotic rescue of HuCCT-1 cells by binding to CXCR4. \r\n\r\n Conclusions: Our study demonstrates that CCA cells migration and survival are modulated by the crosstalk between SDF-1, released by hHSC, and HuCCT-1 cells bearing CXCR4.","Source":"STN","category":"ANIMAL","training_data":"Stromal-Derived Factor-1 (Sdf-1) - Cxcr4 Axis Has An Important Role On The Interaction Of Human Hepatic Stellate Cells (Hhsc) And Cc Cell Lines Backgrounds & aims: Cholangiocarcinoma (CCA) is highly fatal because of early invasion, widespread metastasis, and lack of an effective therapy. Migration, invasion, and metastasis of CCA cells are modulated by signals received from stromal cells. The SDF-1-CXCR4 axis emerges as a pivotal regulator of migration and survival of different tumor cells. The aim of the present study was to characterize the interaction between CCA cells and human hepatic stellate cells (hHSC) focusing on the role of SDF-1. \r\n\r\n Methods: The intrahepatic CCA cell line HuCCT-1 and primary hHSC were used for this study. RNA expression was examined by RTQ-PCR and protein expression by Western blotting. Immunofluorescence microscopy and immunohistochemistry were also employed. Migration of CCA cells was assessed using modified Boyden chambers. \r\n\r\n Results: CXCR4 was clearly expressed in CCA cells of human CCA liver specimens. SDF-1 and hHSC conditioned medium (CM) promoted HuCCT-1 cell migration, which was abrogated by pre-incubation with AMD3100, a non-peptide antagonist of the CXCR4 receptor. In addition, HuCCT-1 cells silenced for CXCR4 did not migrate in presence of SDF-1. Both P-ERK and p-AKT were implicated in HuCCT-1 migration and showed a biphasic trend under stimulation of SDF-1. Finally, SDF-1 induced apoptotic rescue of HuCCT-1 cells by binding to CXCR4. \r\n\r\n Conclusions: Our study demonstrates that CCA cells migration and survival are modulated by the crosstalk between SDF-1, released by hHSC, and HuCCT-1 cells bearing CXCR4. STN","prediction_labels":"ANIMAL"},{"cleaned":"evaluation yap therapeutic target hcc cca background hepatocellular carcinoma hcc cholangiocarcinoma cca outcome dismal incidence rapidly increasing mechanistic understanding limited yap effector hippo signaling pathway oncoprotein promotes cell proliferation inhibits apoptosis genetic manipulation yap results biliary hamartoma hcc therefore hypothesize yap driver liver cancer potential therapeutic target methods expression yap transcriptional targets gpc3 survivin surveyed normal human liver primary liver cancer tissues efficacy yap inhibitor vertepofin survivin inhibitor ym155 tested hcc cca cell lines mtt assay results compared non tumor tissue nuclear yap expression significantly increased hcc icc specimens nuclear yap levels significantly correlate nuclear survivin levels hcc icc tissues gpc3 hcc tissues also found verteporfin ym155 suppressed hcc cca cell proliferation vitro additive effect sorafenib treatment moreover hcc cell lines higher yap expression sensitive verteporfin treatment conclusions findings suggested yap contributes primary liver tumorigenesis likely mediates oncogenic effects modulating survivin expression small molecules target yap survivin activity promising therapeutic strategy treatment hcc cca high yap expression google scholar","probabilities":0.9467213,"Title":"Evaluation Of Yap As A Therapeutic Target In Hcc And Cca","Abstract":"Background\nFor Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the outcome is dismal; incidence is rapidly increasing, and mechanistic understanding is limited. YAP, the effector of Hippo signaling pathway, is an oncoprotein that promotes cell proliferation and inhibits apoptosis. Genetic manipulation of YAP results in biliary hamartoma and HCC. Therefore, we hypothesize that YAP is driver of liver cancer and a potential therapeutic target. \nMethods\nExpression of YAP and its transcriptional targets GPC3 and Survivin was surveyed in normal human liver and primary liver cancer tissues. Efficacy of YAP inhibitor Vertepofin and Survivin inhibitor YM155 was tested in HCC and CCA cell lines with MTT assay.\nResults\nCompared to the non‐tumor tissue, nuclear YAP expression significantly increased in both HCC and ICC specimens. Nuclear YAP levels significantly correlate with nuclear Survivin levels in HCC and ICC tissues, but not with GPC3 in HCC tissues. We also found that verteporfin and YM155 suppressed HCC and CCA cell proliferation in vitro and had an additive effect to sorafenib treatment. Moreover, HCC cell lines with higher YAP expression were more sensitive to verteporfin treatment. \nConclusions\nOur findings suggested that YAP contributes to primary liver tumorigenesis and likely mediates its oncogenic effects through modulating Survivin expression. Small molecules that target YAP and Survivin activity could be a promising therapeutic strategy for treatment of HCC and CCA with high YAP expression.","Source":"Google Scholar","category":"ANIMAL","training_data":"Evaluation Of Yap As A Therapeutic Target In Hcc And Cca Background\nFor Hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA), the outcome is dismal; incidence is rapidly increasing, and mechanistic understanding is limited. YAP, the effector of Hippo signaling pathway, is an oncoprotein that promotes cell proliferation and inhibits apoptosis. Genetic manipulation of YAP results in biliary hamartoma and HCC. Therefore, we hypothesize that YAP is driver of liver cancer and a potential therapeutic target. \nMethods\nExpression of YAP and its transcriptional targets GPC3 and Survivin was surveyed in normal human liver and primary liver cancer tissues. Efficacy of YAP inhibitor Vertepofin and Survivin inhibitor YM155 was tested in HCC and CCA cell lines with MTT assay.\nResults\nCompared to the non‐tumor tissue, nuclear YAP expression significantly increased in both HCC and ICC specimens. Nuclear YAP levels significantly correlate with nuclear Survivin levels in HCC and ICC tissues, but not with GPC3 in HCC tissues. We also found that verteporfin and YM155 suppressed HCC and CCA cell proliferation in vitro and had an additive effect to sorafenib treatment. Moreover, HCC cell lines with higher YAP expression were more sensitive to verteporfin treatment. \nConclusions\nOur findings suggested that YAP contributes to primary liver tumorigenesis and likely mediates its oncogenic effects through modulating Survivin expression. Small molecules that target YAP and Survivin activity could be a promising therapeutic strategy for treatment of HCC and CCA with high YAP expression. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"assessment lymph node status gallbladder cancer location number ratio positive nodes background assessment lymph node status critical issue surgical management gallbladder cancer aim study compare anatomical location positive nodes number positive nodes lymph node ratio lnr prognostic predictors gallbladder cancer methods conducted retrospective analysis 135 patients gallbladder cancer underwent radical resection regional lymphadenectomy total 2 245 regional lymph nodes retrieved median 14 per patient location positive nodes classified according ajcc staging manual 7th edition optimal cutoff values determined number positive nodes lnr based maximal 2 scores calculated cox proportional hazards regression model results lymph node metastasis found histologically 59 44 patients optimal cutoff values number positive nodes lnr determined three nodes 10 respectively univariate analysis identified location positive nodes pn0 pn1 pn2 p 0 001 number positive nodes 0 1 3 4 p 0 001 lnr 0 0 10 10 p 0 001 significant prognostic factors multivariate analysis identified number positive nodes independent prognostic factor p 0 004 however location positive nodes lnr failed remain independent variable conclusions number positive lymph nodes better predicts patient outcome resection either location positive lymph nodes lnr gallbladder cancer dividing number positive lymph nodes three categories 0 1 3 4 valid stratifying patients based prognosis resection pubmed","probabilities":0.9799733,"Title":"Assessment of lymph node status in gallbladder cancer: location, number, or ratio of positive nodes","Abstract":"A BACKGROUND: Assessment of lymph node status is a critical issue in the surgical management of gallbladder cancer. The aim of this study was to compare the anatomical location of positive nodes, number of positive nodes, and lymph node ratio (LNR) as prognostic predictors in gallbladder cancer. METHODS: We conducted a retrospective analysis of 135 patients with gallbladder cancer who underwent a radical resection with regional lymphadenectomy. A total of 2,245 regional lymph nodes were retrieved (median, 14 per patient). The location of positive nodes was classified according to the AJCC staging manual (7th edition). 'Optimal' cutoff values were determined for the number of positive nodes and LNR based on maximal χ(2) scores calculated with the Cox proportional hazards regression model. RESULTS: Lymph node metastasis was found histologically in 59 (44%) patients. The 'optimal' cutoff values for the number of positive nodes and LNR were determined to be three nodes and 10%, respectively. Univariate analysis identified location of positive nodes (pN0, pN1, pN2; P<0.001), number of positive nodes (0, 1 to 3, ≥ 4; P <0.001), and LNR (0%, 0 to 10%, >10%; P<0.001) as significant prognostic factors. Multivariate analysis identified number of positive nodes as an independent prognostic factor ( P=0.004); however, location of positive nodes and LNR failed to remain as an independent variable. CONCLUSIONS: The number of positive lymph nodes better predicts patient outcome after resection than either the location of positive lymph nodes or LNR in gallbladder cancer. Dividing the number of positive lymph nodes into three categories (0, 1 to 3, or ≥ 4) is valid for stratifying patients based on the prognosis after resection.","Source":"PubMed","category":"HUMAN","training_data":"Assessment of lymph node status in gallbladder cancer: location, number, or ratio of positive nodes A BACKGROUND: Assessment of lymph node status is a critical issue in the surgical management of gallbladder cancer. The aim of this study was to compare the anatomical location of positive nodes, number of positive nodes, and lymph node ratio (LNR) as prognostic predictors in gallbladder cancer. METHODS: We conducted a retrospective analysis of 135 patients with gallbladder cancer who underwent a radical resection with regional lymphadenectomy. A total of 2,245 regional lymph nodes were retrieved (median, 14 per patient). The location of positive nodes was classified according to the AJCC staging manual (7th edition). 'Optimal' cutoff values were determined for the number of positive nodes and LNR based on maximal χ(2) scores calculated with the Cox proportional hazards regression model. RESULTS: Lymph node metastasis was found histologically in 59 (44%) patients. The 'optimal' cutoff values for the number of positive nodes and LNR were determined to be three nodes and 10%, respectively. Univariate analysis identified location of positive nodes (pN0, pN1, pN2; P<0.001), number of positive nodes (0, 1 to 3, ≥ 4; P <0.001), and LNR (0%, 0 to 10%, >10%; P<0.001) as significant prognostic factors. Multivariate analysis identified number of positive nodes as an independent prognostic factor ( P=0.004); however, location of positive nodes and LNR failed to remain as an independent variable. CONCLUSIONS: The number of positive lymph nodes better predicts patient outcome after resection than either the location of positive lymph nodes or LNR in gallbladder cancer. Dividing the number of positive lymph nodes into three categories (0, 1 to 3, or ≥ 4) is valid for stratifying patients based on the prognosis after resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical outcomes small cell neuroendocrine carcinoma adenocarcinoma gallbladder aim compare demographics survival rates gallbladder adenocarcinoma gb adenocarcinoma small cell neuroendocrine carcinoma gallbladder gb nec scc methods march 2007 september 2012 patients underwent resection tumor stage t2 t3 gb cancer enrolled study forty two patients included study including 38 diagnosed gb adenocarcinoma four diagnosed gb nec scc gb adenocarcinoma group radical operation performed 28 patients ten patients underwent simple cholecystectomy gb nec scc group radical operation performed three patients one patient underwent simple cholecystectomy comparative analysis two groups performed including clinicopathologic features survival rates results median age patients 68 y range 35 83 years females comprised 26 42 patients gb adenocarcinoma patients significantly older gb nec scc patients 67 89 11 15 vs 55 75 10 31 years p 0 029 median tumor size gb adenocarcinoma patients 2 56 1 75 cm 3 98 3 74 cm gb nec scc patients however significant difference two groups tumors 2 cm stage t2 vs t3 lymphovascular invasion perineural invasion lymph node metastasis lymph node ratio showed significant differences two groups overall survival rate 42 patients five years 77 0 gb adenocarcinoma group overall five year survival rate 74 8 survival gb nec scc group 100 significantly different two groups conclusion strategy treating patients gb nec scc similar used treating gb adenocarcinoma including radical cholecystectomy liver resection pubmed","probabilities":0.962963,"Title":"Clinical outcomes of small cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder","Abstract":"AIM: To compare the demographics and survival rates between gallbladder adenocarcinoma (GB-adenocarcinoma) and small cell neuroendocrine carcinoma of the gallbladder (GB-NEC-SCC). METHODS: From March 2007 to September 2012, patients who underwent resection of tumor stage T2/T3 GB cancer were enrolled for this study. Forty-two patients were included in this study, including 38 diagnosed with GB-adenocarcinoma and four diagnosed with GB-NEC-SCC. In the GB-adenocarcinoma group, a radical operation was performed in 28 patients, and ten patients underwent simple cholecystectomy. In the GB-NEC-SCC group, a radical operation was performed in three patients, and one patient underwent simple cholecystectomy. Comparative analysis of the two groups was performed, including clinicopathologic features and survival rates. RESULTS: The median age of the patients was 68 y (range: 35-83 years) and females comprised 26/42 of the patients. GB-adenocarcinoma patients were significantly older than GB-NEC-SCC patients (67.89 ± 11.15 vs 55.75 ± 10.31 years; P = 0.029). The median tumor size in GB-adenocarcinoma patients was 2.56 ± 1.75 cm and 3.98 ± 3.74 cm in GB-NEC-SCC patients; however, there was no significant difference between the two groups. For tumors > 2 cm, T stage (T2 vs T3), lymphovascular invasion, perineural invasion, lymph node metastasis and lymph node ratio showed no significant differences between the two groups. The overall survival rate of the 42 patients at five years was 77.0%. In the GB-adenocarcinoma group, the overall five-year survival rate was 74.8%, and survival in the GB-NEC-SCC group was 100%, which was not significantly different between the two groups. CONCLUSION: The strategy for treating patients with GB-NEC-SCC should be similar to that used for treating GB-adenocarcinoma, including radical cholecystectomy and liver resection.","Source":"PubMed","category":"HUMAN","training_data":"Clinical outcomes of small cell neuroendocrine carcinoma and adenocarcinoma of the gallbladder AIM: To compare the demographics and survival rates between gallbladder adenocarcinoma (GB-adenocarcinoma) and small cell neuroendocrine carcinoma of the gallbladder (GB-NEC-SCC). METHODS: From March 2007 to September 2012, patients who underwent resection of tumor stage T2/T3 GB cancer were enrolled for this study. Forty-two patients were included in this study, including 38 diagnosed with GB-adenocarcinoma and four diagnosed with GB-NEC-SCC. In the GB-adenocarcinoma group, a radical operation was performed in 28 patients, and ten patients underwent simple cholecystectomy. In the GB-NEC-SCC group, a radical operation was performed in three patients, and one patient underwent simple cholecystectomy. Comparative analysis of the two groups was performed, including clinicopathologic features and survival rates. RESULTS: The median age of the patients was 68 y (range: 35-83 years) and females comprised 26/42 of the patients. GB-adenocarcinoma patients were significantly older than GB-NEC-SCC patients (67.89 ± 11.15 vs 55.75 ± 10.31 years; P = 0.029). The median tumor size in GB-adenocarcinoma patients was 2.56 ± 1.75 cm and 3.98 ± 3.74 cm in GB-NEC-SCC patients; however, there was no significant difference between the two groups. For tumors > 2 cm, T stage (T2 vs T3), lymphovascular invasion, perineural invasion, lymph node metastasis and lymph node ratio showed no significant differences between the two groups. The overall survival rate of the 42 patients at five years was 77.0%. In the GB-adenocarcinoma group, the overall five-year survival rate was 74.8%, and survival in the GB-NEC-SCC group was 100%, which was not significantly different between the two groups. CONCLUSION: The strategy for treating patients with GB-NEC-SCC should be similar to that used for treating GB-adenocarcinoma, including radical cholecystectomy and liver resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"french experience incidental gallbladder cancer abstract available google scholar","probabilities":0.9799733,"Title":"French Experience In Incidental Gallbladder Cancer","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"French Experience In Incidental Gallbladder Cancer Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"discordance prediction prognosis among patients intrahepatic cholangiocarcinoma preoperative vs postoperative perspective background objective current study characterize patients intrahepatic cholangiocarcinoma icc undergoing curative intent surgery discordant preoperative postoperative prediction scores determine factors associated prediction discrepancy methods patients underwent hepatectomy icc 1990 2016 identified multi institutional international database preoperative postoperative prognostic models designed discordant prognostic scores identified multivariable logistic regression analysis completed determined factors associated score discordance results among 1149 patients concordant prediction scores older median age 60 vs 56 likely smaller median tumor size 6 0 vs 7 5 cm p 05 multivariable logistic analysis patients higher neutrophil lymphocyte ratio odds ratio 1 14 95 confidence interval ci 1 09 1 19 higher cea levels 1 25 95 ci 1 04 1 50 larger tumors 1 10 95 ci 1 04 1 15 suspicious lymph nodes 2 05 95 ci 1 25 3 36 likely preoperative postoperative score discordance older patients decreased odds score discordance 0 98 95 ci 0 96 0 99 patients score discordance worse overall survival compared patients concordant scores median 15 9 vs 21 7 months p 05 conclusion score discordance may reflect aggressive variant icc benefit early integration multidisciplinary treatment strategies pubmed","probabilities":0.9799733,"Title":"Discordance in prediction of prognosis among patients with intrahepatic cholangiocarcinoma: A preoperative vs postoperative perspective","Abstract":"BACKGROUND: The objective of the current study was to characterize patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent surgery with discordant preoperative and postoperative prediction scores and determine factors associated with prediction discrepancy. METHODS: Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified in a multi-institutional international database. Preoperative and postoperative prognostic models were designed and discordant prognostic scores were identified. A multivariable logistic regression analysis was completed to determined factors associated with score discordance. RESULTS: Among 1149 patients, those who had concordant prediction scores were older (median age, 60 vs 56), and more likely to have a smaller median tumor size (6.0 vs 7.5 cm) (all P < .05). On multivariable logistic analysis, patients with higher neutrophil-lymphocyte ratio (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.09-1.19), higher CEA levels (OR, 1.25; 95% CI, 1.04-1.50), larger tumors (OR, 1.10; 95% CI, 1.04-1.15) and suspicious lymph nodes (OR, 2.05; 95% CI, 1.25-3.36) were more likely to have preoperative and postoperative score discordance. Older patients had decreased odds of having score discordance (OR, 0.98; 95% CI, 0.96-0.99). Patients with score discordance had worse overall survival compared with patients with concordant scores (median:15.9 vs 21.7 months, P < .05). CONCLUSION: Score discordance may reflect an aggressive variant of ICC that would benefit from early integration of multidisciplinary treatment strategies.","Source":"PubMed","category":"HUMAN","training_data":"Discordance in prediction of prognosis among patients with intrahepatic cholangiocarcinoma: A preoperative vs postoperative perspective BACKGROUND: The objective of the current study was to characterize patients with intrahepatic cholangiocarcinoma (ICC) undergoing curative-intent surgery with discordant preoperative and postoperative prediction scores and determine factors associated with prediction discrepancy. METHODS: Patients who underwent hepatectomy for ICC between 1990 and 2016 were identified in a multi-institutional international database. Preoperative and postoperative prognostic models were designed and discordant prognostic scores were identified. A multivariable logistic regression analysis was completed to determined factors associated with score discordance. RESULTS: Among 1149 patients, those who had concordant prediction scores were older (median age, 60 vs 56), and more likely to have a smaller median tumor size (6.0 vs 7.5 cm) (all P < .05). On multivariable logistic analysis, patients with higher neutrophil-lymphocyte ratio (odds ratio [OR], 1.14; 95% confidence interval [CI], 1.09-1.19), higher CEA levels (OR, 1.25; 95% CI, 1.04-1.50), larger tumors (OR, 1.10; 95% CI, 1.04-1.15) and suspicious lymph nodes (OR, 2.05; 95% CI, 1.25-3.36) were more likely to have preoperative and postoperative score discordance. Older patients had decreased odds of having score discordance (OR, 0.98; 95% CI, 0.96-0.99). Patients with score discordance had worse overall survival compared with patients with concordant scores (median:15.9 vs 21.7 months, P < .05). CONCLUSION: Score discordance may reflect an aggressive variant of ICC that would benefit from early integration of multidisciplinary treatment strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association non alcoholic steatohepatitis intrahepatic cholangiocarcinoma hospital based case control study background study aimed investigate association non alcoholic steatohepatitis nash intrahepatic cholangiocarcinoma icc methods case control study patients underwent surgical resection either icc metastatic liver tumor control group assessed clinical characteristics pathological findings prevalence known icc risk factors patients without known risk factors compared factors including prevalence nash results patients without known risk factors 15 34 patients icc group 13 69 patients control group diagnosed nash univariate analysis showed significantly higher values icc group age p 0 0478 prevalence obesity p 0 0365 nash p 0 0078 serum levels albumin p 0 0051 gamma glutamyl transpeptidase gtp p 0 0006 compared control group multivariate analysis showed age serum levels gtp nash independent risk factors icc patients nash proportion patients hepatic fibrosis significantly higher icc group control group p 0 0014 conclusion nash possible risk factor icc development j surg oncol 2016 113 779 783 2016 wiley periodicals inc pubmed","probabilities":0.9799733,"Title":"The association between non-alcoholic steatohepatitis and intrahepatic cholangiocarcinoma: A hospital based case-control study","Abstract":"BACKGROUND: This study aimed to investigate the association between non-alcoholic steatohepatitis (NASH) and intrahepatic cholangiocarcinoma (ICC). METHODS: This was a case control study of patients who underwent surgical resection either for ICC or for a metastatic liver tumor (the control group). We assessed their clinical characteristics, pathological findings, and the prevalence of known ICC risk factors. For patients without known risk factors, we compared other factors including the prevalence of NASH. RESULTS: In the patients without known risk factors, 15 of 34 patients in the ICC group and 13 of 69 patients in the control group were diagnosed with NASH. Univariate analysis showed significantly higher values in the ICC group for age (P = 0.0478), prevalence of obesity (P = 0.0365) and NASH (P = 0.0078), and serum levels of albumin (P = 0.0051), and gamma-glutamyl transpeptidase (γ-GTP) (P = 0.0006) compared with the control group. Multivariate analysis showed that age and serum levels of γ-GTP and NASH were independent risk factors for ICC. In patients with NASH, the proportion of patients with hepatic fibrosis was significantly higher in the ICC group than in the control group (P = 0.0014). CONCLUSION: NASH is a possible risk factor for ICC development. J. Surg. Oncol. 2016;113:779-783. © 2016 Wiley Periodicals, Inc.","Source":"PubMed","category":"HUMAN","training_data":"The association between non-alcoholic steatohepatitis and intrahepatic cholangiocarcinoma: A hospital based case-control study BACKGROUND: This study aimed to investigate the association between non-alcoholic steatohepatitis (NASH) and intrahepatic cholangiocarcinoma (ICC). METHODS: This was a case control study of patients who underwent surgical resection either for ICC or for a metastatic liver tumor (the control group). We assessed their clinical characteristics, pathological findings, and the prevalence of known ICC risk factors. For patients without known risk factors, we compared other factors including the prevalence of NASH. RESULTS: In the patients without known risk factors, 15 of 34 patients in the ICC group and 13 of 69 patients in the control group were diagnosed with NASH. Univariate analysis showed significantly higher values in the ICC group for age (P = 0.0478), prevalence of obesity (P = 0.0365) and NASH (P = 0.0078), and serum levels of albumin (P = 0.0051), and gamma-glutamyl transpeptidase (γ-GTP) (P = 0.0006) compared with the control group. Multivariate analysis showed that age and serum levels of γ-GTP and NASH were independent risk factors for ICC. In patients with NASH, the proportion of patients with hepatic fibrosis was significantly higher in the ICC group than in the control group (P = 0.0014). CONCLUSION: NASH is a possible risk factor for ICC development. J. Surg. Oncol. 2016;113:779-783. © 2016 Wiley Periodicals, Inc. PubMed","prediction_labels":"HUMAN"},{"cleaned":"skeletal muscle density skeletal muscle mass associated impaired survival patients suspected perihilar cholangiocarcinoma may identify patients risk early death background low skeletal muscle mass associated increased postoperative morbidity worse survival following resection perihilar cholangiocarcinoma phc investigated predictive value skeletal muscle mass density overall survival os patients suspected phc regardless treatment methods baseline characteristics parameters regarding disease treatment collected patients phc 2002 2014 skeletal muscle mass density measured level third lumbar vertebra ct association skeletal muscle mass density os investigated using kaplan meier method cox survival results median os 233 included patients differ without low skeletal muscle mass p 0 203 whereas significantly different median os months observed patients low hr 7 0 95 ci 4 7 9 3 high hr 12 1 95 ci 8 1 16 1 skeletal muscle density p 0 004 low skeletal muscle density independently associated decreased os hr 1 78 95 ci 1 03 3 07 p 0 040 within first 6 months 6 months hr 0 68 95 ci 0 44 1 07 p 0 093 adjusting age tumour size suspected peritoneal distant metastases imaging conclusion time dependent effect skeletal muscle density os found patients phc regardless subsequent treatment low skeletal muscle density may identify patients risk early death stn","probabilities":0.9799733,"Title":"Skeletal Muscle Density But Not Skeletal Muscle Mass Is Associated With Impaired Survival In Patients With Suspected Perihilar Cholangiocarcinoma And May Identify Patients At Risk For Early Death","Abstract":"Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. \r\n\r\n Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. \r\n\r\n Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. \r\n\r\n Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.","Source":"STN","category":"HUMAN","training_data":"Skeletal Muscle Density But Not Skeletal Muscle Mass Is Associated With Impaired Survival In Patients With Suspected Perihilar Cholangiocarcinoma And May Identify Patients At Risk For Early Death Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. \r\n\r\n Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. \r\n\r\n Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. \r\n\r\n Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death. STN","prediction_labels":"HUMAN"},{"cleaned":"genome wide association study identifies snp dcc associated gallbladder cancer japanese population gallbladder cancer gc relatively uncommon cancer higher incidence certain areas including japan difficulty diagnosis prognosis gc poor identify genetic determinants gc conducted genome wide association study gwas 41 gc patients 866 controls association single nucleotide polymorphism snp gc susceptibility evaluated multivariate logistic regression analysis conditioned age gender subjects snps showed suggestive association p 1 10 4 gc examined 30 cases 898 controls snp rs7504990 dcc deleted colorectal cancer 18q21 3 encodes netrin 1 receptor achieved combined p value 7 46 10 8 6 95 95 ci 3 43 14 08 subsequent imputation analysis identified multiple snps similarly strong associations adjacent genomic region loss heterozygosity reported gc cancers reduced expression dcc indicated associated poorly differentiated histological type increased proliferation metastasis loss adhesiveness however due limited sample size investigated replication study functional analysis necessary confirm result association pubmed","probabilities":0.9799733,"Title":"A genome-wide association study identifies SNP in DCC is associated with gallbladder cancer in the Japanese population","Abstract":"Gallbladder cancer (GC) is a relatively uncommon cancer with higher incidence in certain areas including Japan. Because of the difficulty in diagnosis, prognosis of GC is very poor. To identify genetic determinants of GC, we conducted a genome-wide association study (GWAS) in 41 GC patients and 866 controls. Association between each single-nucleotide polymorphism (SNP) with GC susceptibility was evaluated by multivariate logistic regression analysis conditioned on age and gender of subjects. SNPs that showed suggestive association (P<1 × 10(-4)) with GC were further examined in 30 cases and 898 controls. SNP rs7504990 in the DCC (deleted in colorectal cancer, 18q21.3) that encodes a netrin 1 receptor achieved a combined P-value of 7.46 × 10(-8) (OR=6.95; 95% CI=3.43-14.08). Subsequent imputation analysis identified multiple SNPs with similarly strong associations in an adjacent genomic region, where loss of heterozygosity was reported in GC and other cancers. Reduced expression of DCC was indicated to be associated with the poorly differentiated histological type, increased proliferation and metastasis through loss of adhesiveness. However, due to the limited sample size investigated here, further replication study and functional analysis would be necessary to further confirm the result of the association.","Source":"PubMed","category":"HUMAN","training_data":"A genome-wide association study identifies SNP in DCC is associated with gallbladder cancer in the Japanese population Gallbladder cancer (GC) is a relatively uncommon cancer with higher incidence in certain areas including Japan. Because of the difficulty in diagnosis, prognosis of GC is very poor. To identify genetic determinants of GC, we conducted a genome-wide association study (GWAS) in 41 GC patients and 866 controls. Association between each single-nucleotide polymorphism (SNP) with GC susceptibility was evaluated by multivariate logistic regression analysis conditioned on age and gender of subjects. SNPs that showed suggestive association (P<1 × 10(-4)) with GC were further examined in 30 cases and 898 controls. SNP rs7504990 in the DCC (deleted in colorectal cancer, 18q21.3) that encodes a netrin 1 receptor achieved a combined P-value of 7.46 × 10(-8) (OR=6.95; 95% CI=3.43-14.08). Subsequent imputation analysis identified multiple SNPs with similarly strong associations in an adjacent genomic region, where loss of heterozygosity was reported in GC and other cancers. Reduced expression of DCC was indicated to be associated with the poorly differentiated histological type, increased proliferation and metastasis through loss of adhesiveness. However, due to the limited sample size investigated here, further replication study and functional analysis would be necessary to further confirm the result of the association. PubMed","prediction_labels":"HUMAN"},{"cleaned":"chronic hepatitis b c risk factors intrahepatic cholangiocarcinoma meta analysis case control studies introduction incidence intrahepatic cholangiocarcinoma icc increasing worldwide approximately 3000 cases icc diagnosed annually us several recent studies examined chronic hepatitis b c potential risk factors icc mixed results conducted meta analysis case control studies assess role hepatitis b hepatitis c icc aim quantify risk intrahepatic cholangiocarcinoma patients chronic hepatitis b c methods performed systematic search medline embase cochrane library studies without language restriction case control studies evaluating risk intrahepatic cholangiocarcinoma adult patients chronic hepatitis b c also hand searched grey literature major gastrointestinal meetings standardized forms used extract data regarding number cases hepatitis b c intrahepatic cholangiocarcinoma data extracted two reviewers independently summary odds ratio calculated using comprehensive meta analysis software heterogeneity publication bias also assessed random effects model used pooling data results nine studies 1889 icc cases 109364 controls identified assessing risk icc chronic hepatitis b 8 studies 1764 icc cases 195606 controls hepatitis c studies reported us italy china korea japan majority studies hospital based case control studies odds ratio icc chronic hepatitis b 4 57 95 ci 2 80 7 46 increased risk seen western countries 4 78 95 ci 2 36 9 67 asian countries 4 62 95 ci 2 52 8 45 difference seen geographic regions odds icc hepatitis c increased compared patients without hepatitis c 4 70 95 ci 2 75 8 02 risk high western asian countries conclusion patients chronic hepatitis b c increased risk icc association needs confirmed cohort studies strategies screen patient populations icc explored google scholar","probabilities":0.9799733,"Title":"Chronic Hepatitis B And C Are Risk Factors For Intrahepatic Cholangiocarcinoma: A Meta-Analysis Of Case Control Studies","Abstract":"Introduction: The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing worldwide. Approximately 3000 cases of ICC are diagnosed annually in the US. Several recent studies have examined chronic Hepatitis B and C as potential risk factors for ICC with mixed results. We conducted a meta-analysis of case control studies to assess the role of Hepatitis B and Hepatitis C in ICC. Aim: To quantify the risk of intrahepatic cholangiocarcinoma in patients with chronic hepatitis B and C. Methods: We performed a systematic search of Medline, EMBASE and the Cochrane Library for studies without language restriction for case control studies evaluating the risk of intrahepatic cholangiocarcinoma in adult patients with chronic Hepatitis B and C. We also hand searched grey literature from major gastrointestinal meetings. Standardized forms were used to extract data regarding number of cases of Hepatitis B and C and intrahepatic cholangiocarcinoma. Data was extracted by two reviewers independently. Summary odds ratio was calculated using Comprehensive Meta-analysis software. Heterogeneity and publication bias were also assessed. Random effects model was used for pooling the data. Results: Nine studies (1889 ICC cases/ 109364 controls) were identified assessing the risk of ICC in chronic Hepatitis B and 8 studies (1764 ICC cases/195606 controls) in Hepatitis C. The studies were reported from the US, Italy, China, Korea and Japan. The majority of the studies were hospital-based case control studies. The odds ratio of ICC in chronic Hepatitis B was 4.57 ( 95% CI: 2.80 - 7.46). Increased risk was seen both in the Western countries (OR 4.78, 95% CI : 2.36-9.67) and Asian countries (OR 4.62, 95% CI : 2.52-8.45). No difference was seen between the geographic regions. The odds of ICC in Hepatitis C was increased compared to patients without Hepatitis C ( OR 4.70, 95% CI : 2.75-8.02). The risk was high both in the Western and Asian countries. Conclusion: Patients with chronic Hepatitis B and C are at increased risk of ICC. This association needs to be confirmed in cohort studies. Strategies to screen these patient populations for ICC should be explored.","Source":"Google Scholar","category":"HUMAN","training_data":"Chronic Hepatitis B And C Are Risk Factors For Intrahepatic Cholangiocarcinoma: A Meta-Analysis Of Case Control Studies Introduction: The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing worldwide. Approximately 3000 cases of ICC are diagnosed annually in the US. Several recent studies have examined chronic Hepatitis B and C as potential risk factors for ICC with mixed results. We conducted a meta-analysis of case control studies to assess the role of Hepatitis B and Hepatitis C in ICC. Aim: To quantify the risk of intrahepatic cholangiocarcinoma in patients with chronic hepatitis B and C. Methods: We performed a systematic search of Medline, EMBASE and the Cochrane Library for studies without language restriction for case control studies evaluating the risk of intrahepatic cholangiocarcinoma in adult patients with chronic Hepatitis B and C. We also hand searched grey literature from major gastrointestinal meetings. Standardized forms were used to extract data regarding number of cases of Hepatitis B and C and intrahepatic cholangiocarcinoma. Data was extracted by two reviewers independently. Summary odds ratio was calculated using Comprehensive Meta-analysis software. Heterogeneity and publication bias were also assessed. Random effects model was used for pooling the data. Results: Nine studies (1889 ICC cases/ 109364 controls) were identified assessing the risk of ICC in chronic Hepatitis B and 8 studies (1764 ICC cases/195606 controls) in Hepatitis C. The studies were reported from the US, Italy, China, Korea and Japan. The majority of the studies were hospital-based case control studies. The odds ratio of ICC in chronic Hepatitis B was 4.57 ( 95% CI: 2.80 - 7.46). Increased risk was seen both in the Western countries (OR 4.78, 95% CI : 2.36-9.67) and Asian countries (OR 4.62, 95% CI : 2.52-8.45). No difference was seen between the geographic regions. The odds of ICC in Hepatitis C was increased compared to patients without Hepatitis C ( OR 4.70, 95% CI : 2.75-8.02). The risk was high both in the Western and Asian countries. Conclusion: Patients with chronic Hepatitis B and C are at increased risk of ICC. This association needs to be confirmed in cohort studies. Strategies to screen these patient populations for ICC should be explored. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"establishment six new human biliary tract carcinoma cell lines identification mageh1 candidate biomarker predicting efficacy gemcitabine treatment aim study establish new biliary tract carcinoma btc cell lines identify predictive biomarkers potential effectiveness gemcitabine therapy surgical specimens btc transplanted directly immunodeficient mice establish xenografts subjected vitro cell culture gemcitabine sensitivity cell line determined compared genome wide gene expression profile new predictive biomarker candidate validated using additional cohort gemcitabine treated btc cases 55 btc cases established 19 xenografts six new cell lines based gemcitabine sensitivity 10 btc cell lines including six new four publicly available ones clearly categorized two groups mageh1 mrna expression tumor cells showed significant negative correlation sensitivity gemcitabine immunohistochemically mageh1 protein detected three 50 six sensitive cell lines four 100 four resistant cell lines validation cohort gemcitabine treated recurrence cases patients categorized effective non effective groups according recist guidelines assessment chemotherapeutic effects mageh1 protein expression detected two 40 five effective cases four 100 non effective cases established new btc bioresource covers wide range biological features including drug sensitivity linked clinical information negative expression mageh1 protein serves potential predictive marker effectiveness gemcitabine therapy btc stn","probabilities":0.9467213,"Title":"Establishment Of Six New Human Biliary Tract Carcinoma Cell Lines And Identification Of Mageh1 As A Candidate Biomarker For Predicting The Efficacy Of Gemcitabine Treatment","Abstract":"The aim of this study was to establish new biliary tract carcinoma (BTC) cell lines and identify predictive biomarkers for the potential effectiveness of gemcitabine therapy. Surgical specimens of BTC were transplanted directly into immunodeficient mice to establish xenografts, then subjected to in vitro cell culture. The gemcitabine sensitivity of each cell line was determined and compared with the genome-wide gene expression profile. A new predictive biomarker candidate was validated using an additional cohort of gemcitabine-treated BTC cases. From 55 BTC cases, we established 19 xenografts and six new cell lines. Based on their gemcitabine sensitivity, 10 BTC cell lines (including six new and four publicly available ones) were clearly categorized into two groups, and MAGEH1 mRNA expression in the tumor cells showed a significant negative correlation with their sensitivity to gemcitabine. Immunohistochemically, MAGEH1 protein was detected in three (50%) out of six sensitive cell lines, and four (100%) out of four resistant cell lines. In the validation cohort of gemcitabine-treated recurrence cases, patients were categorized into \"effective\" and \"non-effective\" groups according to the RECIST guidelines for assessment of chemotherapeutic effects. MAGEH1 protein expression was detected in two (40%) out of five \"effective\" cases and all four (100%) \"non-effective\" cases. We have established a new BTC bioresource that covers a wide range of biological features, including drug sensitivity, and is linked with clinical information. Negative expression of MAGEH1 protein serves as a potential predictive marker for the effectiveness of gemcitabine therapy in BTC.","Source":"STN","category":"ANIMAL","training_data":"Establishment Of Six New Human Biliary Tract Carcinoma Cell Lines And Identification Of Mageh1 As A Candidate Biomarker For Predicting The Efficacy Of Gemcitabine Treatment The aim of this study was to establish new biliary tract carcinoma (BTC) cell lines and identify predictive biomarkers for the potential effectiveness of gemcitabine therapy. Surgical specimens of BTC were transplanted directly into immunodeficient mice to establish xenografts, then subjected to in vitro cell culture. The gemcitabine sensitivity of each cell line was determined and compared with the genome-wide gene expression profile. A new predictive biomarker candidate was validated using an additional cohort of gemcitabine-treated BTC cases. From 55 BTC cases, we established 19 xenografts and six new cell lines. Based on their gemcitabine sensitivity, 10 BTC cell lines (including six new and four publicly available ones) were clearly categorized into two groups, and MAGEH1 mRNA expression in the tumor cells showed a significant negative correlation with their sensitivity to gemcitabine. Immunohistochemically, MAGEH1 protein was detected in three (50%) out of six sensitive cell lines, and four (100%) out of four resistant cell lines. In the validation cohort of gemcitabine-treated recurrence cases, patients were categorized into \"effective\" and \"non-effective\" groups according to the RECIST guidelines for assessment of chemotherapeutic effects. MAGEH1 protein expression was detected in two (40%) out of five \"effective\" cases and all four (100%) \"non-effective\" cases. We have established a new BTC bioresource that covers a wide range of biological features, including drug sensitivity, and is linked with clinical information. Negative expression of MAGEH1 protein serves as a potential predictive marker for the effectiveness of gemcitabine therapy in BTC. STN","prediction_labels":"ANIMAL"},{"cleaned":"change circulating tissue based mir 20a human cancers associated prognostic implication systematic review meta analysis background previous literatures investigated change mir 20a expression level progression multiple cancers influence patients survival outcome results available evidence inconsistent objective elucidate prognostic value circulating tissue based mir 20a patients various cancers methods systematic search review eligible publications carried three electronic databases including cochrane library pubmed embase methodological quality included studies assessed according newcastle ottawa scale nos hazard ratios hrs corresponding 95 confidence intervals cis overall survival os recurrence free survival rfs disease free survival dfs progressive free survival pfs study pooled using random effect model results total 24 studies involving 4186 samples multiple cancers published 20 articles included statistical analysis circulating mir 20a five kinds cancers containing gastric cancer lymphoma glioblastoma prostate cancer non small cell lung cancer reported upregulated level patients compared normal healthy control overexpressed circulating mir 20a confer unfavorable factor os hr 1 71 95 cis 1 43 2 04 p 0 01 dfs hr 1 90 95 cis 1 45 2 49 p 0 01 tissue based samples 6 kinds malignancies including colorectal cancer salivary adenoid cystic carcinoma gallbladder carcinoma colon cancer gastrointestinal cancer alveolar rhabdomyosarcoma revealed upregulated mir 20a expression level compared paired nontumorous tissue high expression mir 20a significantly associated poor os hr 2 74 95 cis 1 38 5 42 p 0 01 dfs hr 2 68 95 cis 1 32 5 45 p 0 01 meanwhile 5 tumors containing breast cancer cutaneous squamous cell carcinoma hepatocellular carcinoma oral squamous cell carcinoma epithelial ovarian cancer demonstrated downregulated mir 20a expression level compared benign tissue low mir 20a expression significantly related shorter os hr 3 48 95 cis 2 00 6 06 p 0 01 pfs rfs hr 4 05 95 cis 2 89 5 66 p 0 01 conclusion change circulating tissue based mir 20a expression possesses vital prognostic implication human cancers augmented expression circulating mir 20a predicts poor survival outcome patients cancers tissue based mir 20a level may upregulated downregulated depending cancer types former condition high expression tissue mir 20a risk factor unfavorable prognosis latter condition low expression tissue mir 20a associated shorter survival pubmed","probabilities":0.962963,"Title":"Change of Circulating and Tissue-Based miR-20a in Human Cancers and Associated Prognostic Implication: A Systematic Review and Meta-Analysis","Abstract":"BACKGROUND: Previous literatures have investigated the change of miR-20a expression level in the progression of multiple cancers and its influence on patients' survival outcome, but results of now-available evidence are inconsistent. OBJECTIVE: To elucidate the prognostic value of circulating and tissue-based miR-20a for patients with various cancers. METHODS: A systematic search and review of eligible publications were carried out in three electronic databases including the Cochrane Library, PubMed, and Embase, and the methodological quality of included studies was assessed according to Newcastle-Ottawa Scale (NOS). Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and progressive-free survival (PFS) of each study were pooled using a random effect model. RESULTS: In total, 24 studies involving 4186 samples of multiple cancers published in 20 articles were included in the statistical analysis. As for circulating miR-20a, five kinds of cancers containing gastric cancer, lymphoma, glioblastoma, prostate cancer, and non-small-cell lung cancer reported upregulated level in patients compared with normal healthy control, and overexpressed circulating miR-20a could confer an unfavorable factor for OS (HR = 1.71, 95% CIs: 1.43 -2.04, p < 0.01) and DFS (HR = 1.90, 95% CIs: 1.45-2.49, p < 0.01). As for tissue-based samples, 6 kinds of malignancies including colorectal cancer, salivary adenoid cystic carcinoma, gallbladder carcinoma, colon cancer, gastrointestinal cancer, and alveolar rhabdomyosarcoma revealed upregulated miR-20a expression level compared with paired nontumorous tissue, of which high expression of miR-20a was significantly associated with poor OS (HR = 2.74, 95% CIs: 1.38-5.42, p < 0.01) and DFS (HR = 2.68, 95% CIs: 1.32-5.45, p < 0.01); meanwhile, other 5 tumors containing breast cancer, cutaneous squamous cell carcinoma, hepatocellular carcinoma, oral squamous cell carcinoma, and epithelial ovarian cancer demonstrated downregulated miR-20a expression level compared with benign tissue, of which low miR-20a expression was significantly related to shorter OS (HR = 3.48, 95% CIs: 2.00-6.06, p < 0.01) and PFS/RFS (HR = 4.05, 95% CIs: 2.89-5.66, p < 0.01). CONCLUSION: Change of circulating and tissue-based miR-20a expression possesses vital prognostic implication for human cancers. Augmented expression of circulating miR-20a predicts poor survival outcome for patients with cancers. Tissue-based miR-20a level may be upregulated or downregulated depending on cancer types; in the former condition, high expression of tissue miR-20a is a risk factor for unfavorable prognosis and in the latter condition low expression of tissue miR-20a is associated with shorter survival.","Source":"PubMed","category":"HUMAN","training_data":"Change of Circulating and Tissue-Based miR-20a in Human Cancers and Associated Prognostic Implication: A Systematic Review and Meta-Analysis BACKGROUND: Previous literatures have investigated the change of miR-20a expression level in the progression of multiple cancers and its influence on patients' survival outcome, but results of now-available evidence are inconsistent. OBJECTIVE: To elucidate the prognostic value of circulating and tissue-based miR-20a for patients with various cancers. METHODS: A systematic search and review of eligible publications were carried out in three electronic databases including the Cochrane Library, PubMed, and Embase, and the methodological quality of included studies was assessed according to Newcastle-Ottawa Scale (NOS). Hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) for overall survival (OS), recurrence-free survival (RFS), disease-free survival (DFS), and progressive-free survival (PFS) of each study were pooled using a random effect model. RESULTS: In total, 24 studies involving 4186 samples of multiple cancers published in 20 articles were included in the statistical analysis. As for circulating miR-20a, five kinds of cancers containing gastric cancer, lymphoma, glioblastoma, prostate cancer, and non-small-cell lung cancer reported upregulated level in patients compared with normal healthy control, and overexpressed circulating miR-20a could confer an unfavorable factor for OS (HR = 1.71, 95% CIs: 1.43 -2.04, p < 0.01) and DFS (HR = 1.90, 95% CIs: 1.45-2.49, p < 0.01). As for tissue-based samples, 6 kinds of malignancies including colorectal cancer, salivary adenoid cystic carcinoma, gallbladder carcinoma, colon cancer, gastrointestinal cancer, and alveolar rhabdomyosarcoma revealed upregulated miR-20a expression level compared with paired nontumorous tissue, of which high expression of miR-20a was significantly associated with poor OS (HR = 2.74, 95% CIs: 1.38-5.42, p < 0.01) and DFS (HR = 2.68, 95% CIs: 1.32-5.45, p < 0.01); meanwhile, other 5 tumors containing breast cancer, cutaneous squamous cell carcinoma, hepatocellular carcinoma, oral squamous cell carcinoma, and epithelial ovarian cancer demonstrated downregulated miR-20a expression level compared with benign tissue, of which low miR-20a expression was significantly related to shorter OS (HR = 3.48, 95% CIs: 2.00-6.06, p < 0.01) and PFS/RFS (HR = 4.05, 95% CIs: 2.89-5.66, p < 0.01). CONCLUSION: Change of circulating and tissue-based miR-20a expression possesses vital prognostic implication for human cancers. Augmented expression of circulating miR-20a predicts poor survival outcome for patients with cancers. Tissue-based miR-20a level may be upregulated or downregulated depending on cancer types; in the former condition, high expression of tissue miR-20a is a risk factor for unfavorable prognosis and in the latter condition low expression of tissue miR-20a is associated with shorter survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tea consumption reduces incidence gallbladder cancer based meta analysis epidemiologic studies dear editors gallbladder cancer comprises mostly biliary tract malig nancy seventh common digestive system cancers prognosis gallbladder cancer poor whose five year survival reported 5 10 many risk factors gallbladder cancer identified plenty studies definitive association gallstones gallbladder cancer gallbladder polyps bacterial induced chronic inflammation also established risk factors gallbladder ca ncer specific occupa tional exposures petroleum refining example increase incidence gallbladder cancer associated risk factors include sex age post menopausal status cigarette smoking might cause mucosal lesion gallbladder tea derived leaves plant camellia sinensis one popular bev erages worldly green tea black tea popular numerous vitro animal studies proved compounds tea es pecially polyphenols play significant antimutagenic role various cancer date several epidemiologic studies asso ciation tea gallbl adder cancer consistent even contradictory system atic meta analysis elucidate role tea consumption gallbladder cancer far therefore carry meta analysis evaluate association concluded electronic literature search tea gallbladder cancer pubmed embase medline identify relevant human adult studies without language lim itation december 2014 used terms tea gallbladder cancer gallbladder carcinoma gallbladder tumor additi onally reviewed refer ences retrieved articles potential studies epi demiological studies addressed association tween tea intake gallbladder cancer selected potential subjects study provides original data insufficient information odds ratio relative risk rr corresponding 95 confidence intervals cis excluded two independent reviewers read abstracts full text articles assess eligibility stud ies standardized manner extracted important formation including study design country origin years publication origin control number cases control sex distribution kinds tea types cancer comparison exposure level potential confounding variables adjust ed estimates odds ratio relative risk rr associated 95 cis p values also extracted us according equation se ln rr _upper ln rr _ lowel 3 92 calculated se ln rr extracted studies table s1 calculated overall 95 ci among different subgroups three studies using fixed effect model evaluate heterogeneity 2 0 means observed heterogeneity used random effect model calculate summary 95 ci suspecting heterogeneity found heterogeneity obvious calculated summary 95 ci using fixed effect model evaluated impact changes pooled ors study design prior hypotheses explain heterogeneity subgroup analyses considered funnel plot asymmetrical intercept regression line deviated zero p 0 10 publication existed used cochrane collaboration software revman5 0 analyze extracted data fixed random effects model analysis stata stata corp college station usa used conduct egger regression asymmetry test using metabias command google scholar","probabilities":0.8684211,"Title":"Tea Consumption Reduces The Incidence Of Gallbladder Cancer Based On A Meta-Analysis Of Epidemiologic Studies","Abstract":"Dear Editors, \nGallbladder cancer comprises mostly of biliary tract malig-\nnancy which is the seventh most common digestive system \ncancers. The prognosis of gallbladder cancer is poor, whose \nfive-year survival was reported 5%–10%. Many risk factors \nfor gallbladder cancer have been identified in plenty of \nstudies. There has been a definitive association between \ngallstones and gallbladder cancer. Gallbladder polyps and \nbacterial-induced chronic inflammation are also established \nrisk factors for gallbladder ca\nncer. Some specific occupa-\ntional exposures, petroleum refining for example, increase \nthe incidence of gallbladder \ncancer. Other associated risk \nfactors include sex, age, post\nmenopausal status, cigarette \nsmoking and so on, most of which might cause the mucosal \nlesion of gallbladder. Tea, which derived from the leaves of \nthe plant \nCamellia sinensis\n, is one of the most popular bev-\nerages worldly. The green tea and black tea are the most \npopular. Numerous \nin vitro\n and animal studies have proved \nthat the compounds in tea, es\npecially polyphenols, play a \nsignificant antimutagenic role in various cancer. Up to date, \nthere have been several epidemiologic studies on the asso-\nciation between tea and gallbl\nadder cancer, which are not \nconsistent or even contradictory. There has been no system-atic meta-analysis to elucidate the role of tea consumption \non gallbladder cancer so far. Therefore, we carry out this \nmeta-analysis to evaluate the association. \nWe concluded an electronic literature search on tea and \ngallbladder cancer in PubMed, EMBASE and Medline to \nidentify relevant human adult studies without language lim-\nitation until December 2014. The used terms were (“tea” \nand (“gallbladder cancer” or “gallbladder carcinoma” or \n“gallbladder tumor”)). Additi\nonally, we reviewed the refer-\nences from retrieved articles for potential studies. The epi-\ndemiological studies which addressed the association be-\ntween tea intake and gallbladder cancer were selected as \npotential subjects. If the study provides no original data or \ninsufficient information on the odds ratio (\nOR\n) or relative \nrisk (\nRR\n), and their corresponding 95% confidence intervals \n(\nCIs\n), we excluded it. Two independent reviewers read the \nabstracts or full-text articles to assess the eligibility of stud-\nies in a standardized manner. We extracted important in-\nformation including study design, country of origin, years of \npublication, origin of control,\n number of cases and control, \nsex distribution, kinds of tea, types of cancer, comparison of \nexposure level, and potential \nconfounding variables adjust-\ned. The estimates of odds ratio (\nOR\n)/relative risk (\nRR\n), their \nassociated 95% \nCIs\n, and \nP\n-values were also extracted by us. \nAccording to the equation: \nSE\n=(ln\nOR\n/\nRR\n_upper\n\nln\nOR\n/\nRR\n_ \nlowel)/3.92, we calculated the \nSE\n of the ln\nOR\n/\nRR\n extracted \nfrom studies (Table S1). We calculated the overall \nOR\n and their 95% \nCI\n among different subgroups of three studies by \nusing fixed effect model. We evaluate heterogeneity with \nI\n2\nand 0% means that there is no observed heterogeneity. We \nused the random effect model to calculate the summary \nOR\nand its 95% \nCI\n with suspecting heterogeneity. When we \nfound that the heterogeneity was not obvious, we calculated \nthe summary \nOR\n and its 95% \nCI\n using fixed effect model. \nWe evaluated the impact of the changes on the pooled \nORs\nby study design as prior hypotheses to explain heterogeneity \nthrough subgroup analyses. We considered the funnel plot \nto be asymmetrical if the intercept of the regression line \ndeviated from zero with \nP\n<0.10 and the publication existed. \nWe used the Cochrane Collaboration software RevMan5.0 \nto analyze the extracted data \nwith fixed or random effects \nmodel analysis . STATA (Stata\nCorp, College Station, USA) \nwas used to conduct the Egger regression asymmetry test by \nusing the metabias command.","Source":"Google Scholar","category":"HUMAN","training_data":"Tea Consumption Reduces The Incidence Of Gallbladder Cancer Based On A Meta-Analysis Of Epidemiologic Studies Dear Editors, \nGallbladder cancer comprises mostly of biliary tract malig-\nnancy which is the seventh most common digestive system \ncancers. The prognosis of gallbladder cancer is poor, whose \nfive-year survival was reported 5%–10%. Many risk factors \nfor gallbladder cancer have been identified in plenty of \nstudies. There has been a definitive association between \ngallstones and gallbladder cancer. Gallbladder polyps and \nbacterial-induced chronic inflammation are also established \nrisk factors for gallbladder ca\nncer. Some specific occupa-\ntional exposures, petroleum refining for example, increase \nthe incidence of gallbladder \ncancer. Other associated risk \nfactors include sex, age, post\nmenopausal status, cigarette \nsmoking and so on, most of which might cause the mucosal \nlesion of gallbladder. Tea, which derived from the leaves of \nthe plant \nCamellia sinensis\n, is one of the most popular bev-\nerages worldly. The green tea and black tea are the most \npopular. Numerous \nin vitro\n and animal studies have proved \nthat the compounds in tea, es\npecially polyphenols, play a \nsignificant antimutagenic role in various cancer. Up to date, \nthere have been several epidemiologic studies on the asso-\nciation between tea and gallbl\nadder cancer, which are not \nconsistent or even contradictory. There has been no system-atic meta-analysis to elucidate the role of tea consumption \non gallbladder cancer so far. Therefore, we carry out this \nmeta-analysis to evaluate the association. \nWe concluded an electronic literature search on tea and \ngallbladder cancer in PubMed, EMBASE and Medline to \nidentify relevant human adult studies without language lim-\nitation until December 2014. The used terms were (“tea” \nand (“gallbladder cancer” or “gallbladder carcinoma” or \n“gallbladder tumor”)). Additi\nonally, we reviewed the refer-\nences from retrieved articles for potential studies. The epi-\ndemiological studies which addressed the association be-\ntween tea intake and gallbladder cancer were selected as \npotential subjects. If the study provides no original data or \ninsufficient information on the odds ratio (\nOR\n) or relative \nrisk (\nRR\n), and their corresponding 95% confidence intervals \n(\nCIs\n), we excluded it. Two independent reviewers read the \nabstracts or full-text articles to assess the eligibility of stud-\nies in a standardized manner. We extracted important in-\nformation including study design, country of origin, years of \npublication, origin of control,\n number of cases and control, \nsex distribution, kinds of tea, types of cancer, comparison of \nexposure level, and potential \nconfounding variables adjust-\ned. The estimates of odds ratio (\nOR\n)/relative risk (\nRR\n), their \nassociated 95% \nCIs\n, and \nP\n-values were also extracted by us. \nAccording to the equation: \nSE\n=(ln\nOR\n/\nRR\n_upper\n\nln\nOR\n/\nRR\n_ \nlowel)/3.92, we calculated the \nSE\n of the ln\nOR\n/\nRR\n extracted \nfrom studies (Table S1). We calculated the overall \nOR\n and their 95% \nCI\n among different subgroups of three studies by \nusing fixed effect model. We evaluate heterogeneity with \nI\n2\nand 0% means that there is no observed heterogeneity. We \nused the random effect model to calculate the summary \nOR\nand its 95% \nCI\n with suspecting heterogeneity. When we \nfound that the heterogeneity was not obvious, we calculated \nthe summary \nOR\n and its 95% \nCI\n using fixed effect model. \nWe evaluated the impact of the changes on the pooled \nORs\nby study design as prior hypotheses to explain heterogeneity \nthrough subgroup analyses. We considered the funnel plot \nto be asymmetrical if the intercept of the regression line \ndeviated from zero with \nP\n<0.10 and the publication existed. \nWe used the Cochrane Collaboration software RevMan5.0 \nto analyze the extracted data \nwith fixed or random effects \nmodel analysis . STATA (Stata\nCorp, College Station, USA) \nwas used to conduct the Egger regression asymmetry test by \nusing the metabias command. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"novel clinical factor d dimer platelet multiplication may predict postoperative recurrence prognosis patients cholangiocarcinoma background patients cholangiocarcinoma cc poor prognosis postoperative survival depends cancer progression recurrence thus prognostic markers needed fibrin cleavage product d dimer associated malignant progression recurrence various cancers platelets also related tumor progression study therefore evaluated new prognostic factor d dimer platelet multiplication pdm predicting prognosis cases cc methods study retrospectively evaluated 55 cases determine correlations d dimer platelet pdm levels patient survival cutoff values d dimer platelets pdm levels determined using receiver operating characteristic curve analyses results recurrence group exhibited significantly higher d dimer p 0 00075 pdm p 0 0000683 levels trend toward higher platelet levels p 0 117 optimal cutoff values 1 3 g ml d dimer levels 245 104 l platelet levels 158 2 104 g ml l pdm levels poor recurrence free survival associated high d dimer levels p 0 0428 high platelet levels p 0 0498 high pdm levels p 0 00511 poor cancer specific survival associated high platelet levels p 0 0156 high pdm levels p 0 0156 multivariate analysis pdm greatest correlation cc prognosis independently predicted recurrence p 0 00649 conclusion high d dimer platelet pdm levels associated poor recurrence free cancer specific survivals pdm exhibiting greatest correlation prognosis therefore pdm may help predict recurrence prognosis patients cc pubmed","probabilities":0.9799733,"Title":"A Novel Clinical Factor, D-Dimer Platelet Multiplication, May Predict Postoperative Recurrence and Prognosis for Patients with Cholangiocarcinoma","Abstract":"BACKGROUND: Patients with cholangiocarcinoma (CC) have a poor prognosis, and their postoperative survival depends on cancer progression and recurrence. Thus, prognostic markers are needed. The fibrin cleavage product, D-dimer, is associated with malignant progression and recurrence in various cancers, and platelets also are related to tumor progression. This study therefore evaluated a new prognostic factor, D-dimer platelet multiplication (PDM), for predicting prognosis in cases of CC. METHODS: This study retrospectively evaluated 55 cases to determine the correlations of D-dimer, platelet, and PDM levels with patient survival. The cutoff values for D-dimer, platelets, and PDM levels were determined using receiver operating characteristic curve analyses. RESULTS: The recurrence group exhibited significantly higher D-dimer (P = 0.00075) and PDM (P = 0.0000683) levels and a trend toward higher platelet levels (P = 0.117). The optimal cutoff values were 1.3 µg/mL for D-dimer levels, 245 × 104/µL for platelet levels, and 158.2 × 104 µg/mL × µL for PDM levels. Poor recurrence-free survival was associated with high D-dimer levels (P = 0.0428), high platelet levels (P = 0.0498), and high PDM levels (P = 0.00511). Poor cancer-specific survival was associated with high platelet levels (P = 0.0156) and high PDM levels (P = 0.0156). In the multivariate analysis, PDM had the greatest correlation with CC prognosis and independently predicted recurrence (P = 0.00649). CONCLUSION: High D-dimer, platelet, and PDM levels were associated with poor recurrence-free and cancer-specific survivals, with PDM exhibiting the greatest correlation with prognosis. Therefore, PDM may help to predict recurrence and prognosis for patients with CC.","Source":"PubMed","category":"HUMAN","training_data":"A Novel Clinical Factor, D-Dimer Platelet Multiplication, May Predict Postoperative Recurrence and Prognosis for Patients with Cholangiocarcinoma BACKGROUND: Patients with cholangiocarcinoma (CC) have a poor prognosis, and their postoperative survival depends on cancer progression and recurrence. Thus, prognostic markers are needed. The fibrin cleavage product, D-dimer, is associated with malignant progression and recurrence in various cancers, and platelets also are related to tumor progression. This study therefore evaluated a new prognostic factor, D-dimer platelet multiplication (PDM), for predicting prognosis in cases of CC. METHODS: This study retrospectively evaluated 55 cases to determine the correlations of D-dimer, platelet, and PDM levels with patient survival. The cutoff values for D-dimer, platelets, and PDM levels were determined using receiver operating characteristic curve analyses. RESULTS: The recurrence group exhibited significantly higher D-dimer (P = 0.00075) and PDM (P = 0.0000683) levels and a trend toward higher platelet levels (P = 0.117). The optimal cutoff values were 1.3 µg/mL for D-dimer levels, 245 × 104/µL for platelet levels, and 158.2 × 104 µg/mL × µL for PDM levels. Poor recurrence-free survival was associated with high D-dimer levels (P = 0.0428), high platelet levels (P = 0.0498), and high PDM levels (P = 0.00511). Poor cancer-specific survival was associated with high platelet levels (P = 0.0156) and high PDM levels (P = 0.0156). In the multivariate analysis, PDM had the greatest correlation with CC prognosis and independently predicted recurrence (P = 0.00649). CONCLUSION: High D-dimer, platelet, and PDM levels were associated with poor recurrence-free and cancer-specific survivals, with PDM exhibiting the greatest correlation with prognosis. Therefore, PDM may help to predict recurrence and prognosis for patients with CC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparative outcomes elderly non elderly patients receiving first line palliative chemotherapy advanced biliary tract cancer background aim studies reported efficacy safety palliative chemotherapy elderly patients advanced biliary tract cancer aimed investigate clinical outcomes palliative chemotherapy advanced biliary tract cancer elderly patients methods retrospectively evaluated 403 consecutive patients received palliative chemotherapy april 2006 march 2009 pathologically confirmed unresectable recurrent biliary tract cancer clinical outcomes elderly group 75 years old n 94 compared non elderly group 75 years old n 309 results except extent disease patient baseline characteristics well balanced groups median overall survival 10 4 months elderly group 11 5 months non elderly group hazard ratio 1 14 95 confidence interval 0 89 1 45 p 0 31 although frequency adverse events groups similar interstitial pneumonitis significantly frequent elderly group non elderly group 4 3 vs 0 p 0 01 conclusions advanced biliary tract cancer overall survival elderly patients receiving palliative chemotherapy comparable non elderly patients knowledge one largest studies reported clinical outcomes elderly patients following palliative chemotherapy pubmed","probabilities":0.9799733,"Title":"Comparative outcomes of elderly and non-elderly patients receiving first-line palliative chemotherapy for advanced biliary tract cancer","Abstract":"BACKGROUND AND AIM: Few studies have reported the efficacy and safety of palliative chemotherapy in elderly patients with advanced biliary tract cancer. We aimed to investigate the clinical outcomes of palliative chemotherapy for advanced biliary tract cancer in elderly patients. METHODS: We retrospectively evaluated 403 consecutive patients who received palliative chemotherapy between April 2006 and March 2009 for pathologically confirmed unresectable or recurrent biliary tract cancer. Clinical outcomes of the elderly group (≥ 75 years old; n = 94) were compared with those of the non-elderly group (< 75 years old; n = 309). RESULTS: Except for the extent of disease, patient baseline characteristics were well balanced between both groups. The median overall survival was 10.4 months in the elderly group and 11.5 months in the non-elderly group (hazard ratio, 1.14; 95% confidence interval, 0.89-1.45; P = 0.31). Although the frequency of adverse events between both groups was similar, interstitial pneumonitis was significantly more frequent in the elderly group than in the non-elderly group (4.3% vs 0%, P < 0.01). CONCLUSIONS: In advanced biliary tract cancer, overall survival of elderly patients receiving palliative chemotherapy is comparable with that of non-elderly patients. To our knowledge, this is one of the largest studies that have reported the clinical outcomes of elderly patients following palliative chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Comparative outcomes of elderly and non-elderly patients receiving first-line palliative chemotherapy for advanced biliary tract cancer BACKGROUND AND AIM: Few studies have reported the efficacy and safety of palliative chemotherapy in elderly patients with advanced biliary tract cancer. We aimed to investigate the clinical outcomes of palliative chemotherapy for advanced biliary tract cancer in elderly patients. METHODS: We retrospectively evaluated 403 consecutive patients who received palliative chemotherapy between April 2006 and March 2009 for pathologically confirmed unresectable or recurrent biliary tract cancer. Clinical outcomes of the elderly group (≥ 75 years old; n = 94) were compared with those of the non-elderly group (< 75 years old; n = 309). RESULTS: Except for the extent of disease, patient baseline characteristics were well balanced between both groups. The median overall survival was 10.4 months in the elderly group and 11.5 months in the non-elderly group (hazard ratio, 1.14; 95% confidence interval, 0.89-1.45; P = 0.31). Although the frequency of adverse events between both groups was similar, interstitial pneumonitis was significantly more frequent in the elderly group than in the non-elderly group (4.3% vs 0%, P < 0.01). CONCLUSIONS: In advanced biliary tract cancer, overall survival of elderly patients receiving palliative chemotherapy is comparable with that of non-elderly patients. To our knowledge, this is one of the largest studies that have reported the clinical outcomes of elderly patients following palliative chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"loss bap1 expression occurs frequently intrahepatic cholangiocarcinoma brca1 associated protein 1 bap1 deubiquitinating enzyme functions tumor suppressor gene double hit bap1 inactivation reported range tumor types including intrahepatic cholangiocarcinoma icc sometimes association germline mutation performed immunohistochemistry bap1 well characterized cohort 211 icc patients undergoing surgical resection curative intent 3 institutions based 3 different countries median age diagnosis 65 years range 36 5 86 108 51 men negative staining bap1 defined completely absent nuclear staining presence positive internal controls nonneoplastic cells occurred 55 iccs 26 bap1 loss predicted strong trend toward improved median survival 40 80 months 95 ci 28 14 53 46 versus 24 87 months 95 ci 18 73 31 01 p 0 059 multivariate model including age sex bap1 status tumor stage tumor grade lymphovascular invasion tumor size female sex associated improved survival hazard ratio hr 0 54 95 ci 0 34 0 85 advanced tumor stage lymphovascular invasion hr 1 89 95 ci 1 09 3 28 correlated decreased survival multivariate analysis high grade tumors associated bap1 loss odds ratio 3 32 95 ci 1 29 8 55 lymphatic invasion inversely associated bap1 loss 0 36 95 ci 0 13 0 99 conclusion observed trend toward improved prognosis icc associated absent expression bap1 association bap1 loss higher histological grade absent lymphatic invasion female sex associated improved survival advanced tumor stage lymphatic invasion associated decreased survival pubmed","probabilities":0.9799733,"Title":"Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma","Abstract":"BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that functions as a tumor suppressor gene. Double hit BAP1 inactivation has been reported in a range of tumor types, including intrahepatic cholangiocarcinoma (ICC), sometimes in association with germline mutation.We performed immunohistochemistry for BAP1 on a well-characterized cohort of 211 ICC patients undergoing surgical resection with curative intent at 3 institutions based in 3 different countries. The median age at diagnosis was 65 years (range, 36.5-86) and 108 (51%) were men. Negative staining for BAP1 (defined as completely absent nuclear staining in the presence of positive internal controls in nonneoplastic cells) occurred in 55 ICCs (26%). BAP1 loss predicted a strong trend toward improved median survival of 40.80 months (95% CI, 28.14-53.46) versus 24.87 months (95% CI, 18.73-31.01), P = 0.059). In a multivariate model including age, sex, BAP1 status, tumor stage, tumor grade, lymphovascular invasion, and tumor size, female sex was associated with improved survival (hazard ratio [HR] 0.54; 95% CI, 0.34-0.85), while advanced tumor stage and lymphovascular invasion (HR 1.89; 95% CI, 1.09-3.28) correlated with decreased survival. In a multivariate analysis, high grade tumors were associated with BAP1 loss (odds ratio [OR] 3.32; 95% CI, 1.29-8.55), while lymphatic invasion was inversely associated with BAP1 loss (OR 0.36; 95% CI, 0.13-0.99).In conclusion, we observed a trend toward improved prognosis in ICC associated with absent expression of BAP1 and an association of BAP1 loss with higher histological grade and absent lymphatic invasion. Female sex was associated with improved survival while advanced tumor stage and lymphatic invasion were associated with decreased survival.","Source":"PubMed","category":"HUMAN","training_data":"Loss of BAP1 Expression Occurs Frequently in Intrahepatic Cholangiocarcinoma BRCA1-associated protein 1 (BAP1) is a deubiquitinating enzyme that functions as a tumor suppressor gene. Double hit BAP1 inactivation has been reported in a range of tumor types, including intrahepatic cholangiocarcinoma (ICC), sometimes in association with germline mutation.We performed immunohistochemistry for BAP1 on a well-characterized cohort of 211 ICC patients undergoing surgical resection with curative intent at 3 institutions based in 3 different countries. The median age at diagnosis was 65 years (range, 36.5-86) and 108 (51%) were men. Negative staining for BAP1 (defined as completely absent nuclear staining in the presence of positive internal controls in nonneoplastic cells) occurred in 55 ICCs (26%). BAP1 loss predicted a strong trend toward improved median survival of 40.80 months (95% CI, 28.14-53.46) versus 24.87 months (95% CI, 18.73-31.01), P = 0.059). In a multivariate model including age, sex, BAP1 status, tumor stage, tumor grade, lymphovascular invasion, and tumor size, female sex was associated with improved survival (hazard ratio [HR] 0.54; 95% CI, 0.34-0.85), while advanced tumor stage and lymphovascular invasion (HR 1.89; 95% CI, 1.09-3.28) correlated with decreased survival. In a multivariate analysis, high grade tumors were associated with BAP1 loss (odds ratio [OR] 3.32; 95% CI, 1.29-8.55), while lymphatic invasion was inversely associated with BAP1 loss (OR 0.36; 95% CI, 0.13-0.99).In conclusion, we observed a trend toward improved prognosis in ICC associated with absent expression of BAP1 and an association of BAP1 loss with higher histological grade and absent lymphatic invasion. Female sex was associated with improved survival while advanced tumor stage and lymphatic invasion were associated with decreased survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"nomogram predict long term survival resection intrahepatic cholangiocarcinoma eastern western experience importance intrahepatic cholangiocarcinoma icc primary cancer liver increasing incidence prognostic factors associated outcome surgery remain poorly defined objective combine clinicopathologic variables associated overall survival resection icc prediction nomogram design setting participants performed international multicenter study 514 patients underwent resection icc 13 major hepatobiliary centers united states europe asia may 1 1990 december 31 2011 multivariate cox proportional hazards regression modeling backward selection using akaike information criteria used select variables construction nomogram discrimination calibration performed using kaplan meier curves calibration plots interventions surgical resection icc participating hospital main outcomes measures long term survival effect potential prognostic factors performance proposed nomogram results median patient age 59 2 years 53 1 patients male patients 74 7 solitary tumor median tumor size 6 0 cm patients treated extended hepatectomy 202 39 3 hemihepatectomy 180 35 0 minor liver resection 3 segments 132 25 7 patients underwent r0 resection 87 9 35 7 patients n1 disease using backward selection clinically relevant variables found age diagnosis hazard ratio hr 1 31 p 001 tumor size hr 1 50 p 001 multiple tumors hr 1 58 p 001 cirrhosis hr 1 51 p 08 lymph node metastasis hr 1 78 p 01 macrovascular invasion hr 2 10 p 001 selected factors predictive survival basis factors nomogram created predict survival icc resection discrimination using kaplan meier curves calibration curves bootstrap cross validation revealed good predictive abilities c index 0 692 conclusions relevance basis eastern western experience nomogram developed predict overall survival resection icc validation revealed good discrimination calibration suggesting clinical utility improve individualized predictions survival patients undergoing resection icc pubmed","probabilities":0.9799733,"Title":"A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience","Abstract":"IMPORTANCE: Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the liver that is increasing in incidence, and the prognostic factors associated with outcome after surgery remain poorly defined. OBJECTIVE: To combine clinicopathologic variables associated with overall survival after resection of ICC into a prediction nomogram. DESIGN, SETTING, AND PARTICIPANTS: We performed an international multicenter study of 514 patients who underwent resection for ICC at 13 major hepatobiliary centers in the United States, Europe, and Asia from May 1, 1990, through December 31, 2011. Multivariate Cox proportional hazards regression modeling with backward selection using the Akaike information criteria was used to select variables for construction of the nomogram. Discrimination and calibration were performed using Kaplan-Meier curves and calibration plots. INTERVENTIONS: Surgical resection of ICC at a participating hospital. MAIN OUTCOMES AND MEASURES: Long-term survival, effect of potential prognostic factors, and performance of proposed nomogram. RESULTS: Median patient age was 59.2 years, and 53.1% of the patients were male. Most patients (74.7%) had a solitary tumor, and median tumor size was 6.0 cm. Patients were treated with an extended hepatectomy (202 [39.3%]), a hemihepatectomy (180 [35.0%]), or a minor liver resection (<3 segments) (132 [25.7%]). Most patients underwent R0 resection (87.9%), and 35.7% of patients had N1 disease. Using the backward selection of clinically relevant variables, we found that age at diagnosis (hazard ratio [HR], 1.31; P < .001), tumor size (HR, 1.50; P < .001), multiple tumors (HR, 1.58; P < .001), cirrhosis (HR, 1.51; P = .08), lymph node metastasis (HR, 1.78; P = .01), and macrovascular invasion (HR, 2.10; P < .001) were selected as factors predictive of survival. On the basis of these factors, a nomogram was created to predict survival of ICC after resection. Discrimination using Kaplan-Meier curves, calibration curves, and bootstrap cross-validation revealed good predictive abilities (C index, 0.692). CONCLUSIONS AND RELEVANCE: On the basis of an Eastern and Western experience, a nomogram was developed to predict overall survival after resection for ICC. Validation revealed good discrimination and calibration, suggesting clinical utility to improve individualized predictions of survival for patients undergoing resection of ICC.","Source":"PubMed","category":"HUMAN","training_data":"A nomogram to predict long-term survival after resection for intrahepatic cholangiocarcinoma: an Eastern and Western experience IMPORTANCE: Intrahepatic cholangiocarcinoma (ICC) is a primary cancer of the liver that is increasing in incidence, and the prognostic factors associated with outcome after surgery remain poorly defined. OBJECTIVE: To combine clinicopathologic variables associated with overall survival after resection of ICC into a prediction nomogram. DESIGN, SETTING, AND PARTICIPANTS: We performed an international multicenter study of 514 patients who underwent resection for ICC at 13 major hepatobiliary centers in the United States, Europe, and Asia from May 1, 1990, through December 31, 2011. Multivariate Cox proportional hazards regression modeling with backward selection using the Akaike information criteria was used to select variables for construction of the nomogram. Discrimination and calibration were performed using Kaplan-Meier curves and calibration plots. INTERVENTIONS: Surgical resection of ICC at a participating hospital. MAIN OUTCOMES AND MEASURES: Long-term survival, effect of potential prognostic factors, and performance of proposed nomogram. RESULTS: Median patient age was 59.2 years, and 53.1% of the patients were male. Most patients (74.7%) had a solitary tumor, and median tumor size was 6.0 cm. Patients were treated with an extended hepatectomy (202 [39.3%]), a hemihepatectomy (180 [35.0%]), or a minor liver resection (<3 segments) (132 [25.7%]). Most patients underwent R0 resection (87.9%), and 35.7% of patients had N1 disease. Using the backward selection of clinically relevant variables, we found that age at diagnosis (hazard ratio [HR], 1.31; P < .001), tumor size (HR, 1.50; P < .001), multiple tumors (HR, 1.58; P < .001), cirrhosis (HR, 1.51; P = .08), lymph node metastasis (HR, 1.78; P = .01), and macrovascular invasion (HR, 2.10; P < .001) were selected as factors predictive of survival. On the basis of these factors, a nomogram was created to predict survival of ICC after resection. Discrimination using Kaplan-Meier curves, calibration curves, and bootstrap cross-validation revealed good predictive abilities (C index, 0.692). CONCLUSIONS AND RELEVANCE: On the basis of an Eastern and Western experience, a nomogram was developed to predict overall survival after resection for ICC. Validation revealed good discrimination and calibration, suggesting clinical utility to improve individualized predictions of survival for patients undergoing resection of ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"covered stents versus uncovered stents palliation malignant extrahepatic biliary obstruction caused direct tumor invasion cohort comparative study biliary stenting well established palliative treatment patients unresectable malignant biliary strictures aim present study compare clinical outcomes covered uncovered stents patients malignant extrahepatic biliary obstruction caused direct tumor invasion patients diagnosed malignant extrahepatic biliary obstruction caused direct tumor invasion enrolled study patients 37 received eptfe covered stent placement prospectively studied 47 received uncovered stent placement retrospectively studied technical success rate tumor ingrowth rate complication rate stent patency patient survival evaluated groups stent placement successful cases except one covered group due stent kinking tumor ingrowth occurred exclusively uncovered group significant differences observed complication rate patient survival two groups three patients covered group experienced stent migration whereas patients uncovered group significant difference found regarding stent patency greater covered group compared uncovered group placement eptfe covered stents treatment malignant biliary obstruction caused direct tumor invasion safe effective method characterized greater stent patency pubmed","probabilities":0.9799733,"Title":"Covered stents versus uncovered stents for the palliation of malignant extrahepatic biliary obstruction caused by direct tumor invasion: a cohort comparative study","Abstract":"Biliary stenting is a well-established palliative treatment in patients with unresectable malignant biliary strictures. The aim of the present study was to compare clinical outcomes of covered and uncovered stents in patients with malignant extrahepatic biliary obstruction caused by direct tumor invasion. Patients diagnosed with malignant extrahepatic biliary obstruction caused by direct tumor invasion were enrolled in this study. Of these patients, 37 received ePTFE-covered stent placement and were prospectively studied, and 47 received uncovered stent placement and were retrospectively studied. The technical success rate, tumor ingrowth rate, complication rate, stent patency, and patient survival were evaluated for both groups. Stent placement was successful in all cases except one in the covered group due to stent kinking. Tumor ingrowth occurred exclusively in the uncovered group. No significant differences were observed for the complication rate and patient survival between the two groups. Three patients in the covered group experienced stent migration, whereas no patients did in the uncovered group. A significant difference was found regarding stent patency, which was greater for the covered group compared to the uncovered group. The placement of ePTFE-covered stents for the treatment of malignant biliary obstruction caused by direct tumor invasion was a safe and an effective method characterized by greater stent patency.","Source":"PubMed","category":"HUMAN","training_data":"Covered stents versus uncovered stents for the palliation of malignant extrahepatic biliary obstruction caused by direct tumor invasion: a cohort comparative study Biliary stenting is a well-established palliative treatment in patients with unresectable malignant biliary strictures. The aim of the present study was to compare clinical outcomes of covered and uncovered stents in patients with malignant extrahepatic biliary obstruction caused by direct tumor invasion. Patients diagnosed with malignant extrahepatic biliary obstruction caused by direct tumor invasion were enrolled in this study. Of these patients, 37 received ePTFE-covered stent placement and were prospectively studied, and 47 received uncovered stent placement and were retrospectively studied. The technical success rate, tumor ingrowth rate, complication rate, stent patency, and patient survival were evaluated for both groups. Stent placement was successful in all cases except one in the covered group due to stent kinking. Tumor ingrowth occurred exclusively in the uncovered group. No significant differences were observed for the complication rate and patient survival between the two groups. Three patients in the covered group experienced stent migration, whereas no patients did in the uncovered group. A significant difference was found regarding stent patency, which was greater for the covered group compared to the uncovered group. The placement of ePTFE-covered stents for the treatment of malignant biliary obstruction caused by direct tumor invasion was a safe and an effective method characterized by greater stent patency. PubMed","prediction_labels":"HUMAN"},{"cleaned":"irinotecan plus gemcitabine fluorouracil advanced biliary tract cancer retrospective study background since 2010 combination therapy gemcitabine cisplatin standard treatment patients biliary tract cancer btc based abc 02 trial however treatment first line progression less clearly defined therefore retrospectively analyzed efficacy 3 drug chemotherapy regimen patients advanced btc methods patients advanced btc treated palliative chemotherapy april 2000 october 2005 regensburg university hospital reviewed retrospectively analyzed efficacy safety institutional standard 3 drug regimen consisting irinotecan gemcitabine 5 fu igf one cycle lasting 21 days included applications days 1 8 consisting 75 mg m2 irinotecan v 90 min 1 000 mg m2 gemcitabine v 30 min 2 000 mg m2 fluorouracil 5 fu 24 h results total 12 histologically confirmed cases gallbladder cancer intrahepatic btc reviewed fifty percent patients 6 12 pretreated chemotherapies median progression free survival 9 4 months 1 5 21 5 median overall survival 17 2 months 2 5 24 3 neutropenia 8 observed nci ctc grade 3 toxicity anemia leucopenia grades 1 2 common side effects conclusions combination igf shows promising survival benefit manageable toxicity patients advanced btc therefore regimen seems feasible second line treatment option patients rapid progression first line therapy gemcitabine cisplatin good performance status pubmed","probabilities":0.9799733,"Title":"Irinotecan Plus Gemcitabine and Fluorouracil in Advanced Biliary Tract Cancer: A Retrospective Study","Abstract":"BACKGROUND: Since 2010, combination therapy with gemcitabine and cisplatin is the standard treatment for patients with biliary tract cancer (BTC) based on the ABC-02 trial. However, treatment after first-line progression is less clearly defined. We therefore retrospectively analyzed the efficacy of a 3-drug chemotherapy regimen in patients with advanced BTC. METHODS: Patients with advanced BTC treated with palliative chemotherapy between April 2000 and October 2005 at Regensburg University Hospital were reviewed retrospectively. We analyzed the efficacy and safety of an institutional standard 3-drug regimen consisting of irinotecan, gemcitabine and 5-FU (IGF). One cycle, lasting 21 days, included applications on days 1 and 8 consisting of 75 mg/m2 irinotecan i.v. for 90 min, 1,000 mg/m2 gemcitabine i.v. for 30 min and 2,000 mg/m2 fluorouracil (5-FU) for 24 h. RESULTS: A total of 12 histologically confirmed cases with gallbladder cancer and intrahepatic BTC were reviewed. Fifty percent of the patients (6/12) had been pretreated with other chemotherapies. Median progression-free survival was 9.4 months (1.5-21.5) and median overall survival was 17.2 months (2.5-24.3). Only neutropenia (8%) was observed as an NCI-CTC grade 3 toxicity. Anemia and leucopenia grades 1 and 2 were the most common side effects. CONCLUSIONS: The combination of IGF shows a promising survival benefit with manageable toxicity in patients with advanced BTC. Therefore, this regimen seems to be a feasible second-line treatment option for patients with rapid progression under first-line therapy with gemcitabine and cisplatin and with a good performance status.","Source":"PubMed","category":"HUMAN","training_data":"Irinotecan Plus Gemcitabine and Fluorouracil in Advanced Biliary Tract Cancer: A Retrospective Study BACKGROUND: Since 2010, combination therapy with gemcitabine and cisplatin is the standard treatment for patients with biliary tract cancer (BTC) based on the ABC-02 trial. However, treatment after first-line progression is less clearly defined. We therefore retrospectively analyzed the efficacy of a 3-drug chemotherapy regimen in patients with advanced BTC. METHODS: Patients with advanced BTC treated with palliative chemotherapy between April 2000 and October 2005 at Regensburg University Hospital were reviewed retrospectively. We analyzed the efficacy and safety of an institutional standard 3-drug regimen consisting of irinotecan, gemcitabine and 5-FU (IGF). One cycle, lasting 21 days, included applications on days 1 and 8 consisting of 75 mg/m2 irinotecan i.v. for 90 min, 1,000 mg/m2 gemcitabine i.v. for 30 min and 2,000 mg/m2 fluorouracil (5-FU) for 24 h. RESULTS: A total of 12 histologically confirmed cases with gallbladder cancer and intrahepatic BTC were reviewed. Fifty percent of the patients (6/12) had been pretreated with other chemotherapies. Median progression-free survival was 9.4 months (1.5-21.5) and median overall survival was 17.2 months (2.5-24.3). Only neutropenia (8%) was observed as an NCI-CTC grade 3 toxicity. Anemia and leucopenia grades 1 and 2 were the most common side effects. CONCLUSIONS: The combination of IGF shows a promising survival benefit with manageable toxicity in patients with advanced BTC. Therefore, this regimen seems to be a feasible second-line treatment option for patients with rapid progression under first-line therapy with gemcitabine and cisplatin and with a good performance status. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance 18f fdg pet ct patients distal bile duct cancer undergoing curative surgery purpose previous studies small number subjects purpose evaluate prognostic significance 18f fdg pet ct patients distal bile duct cancer undergoing curative surgery methods study included 40 patients m f 24 16 age 68 0 8 0 years underwent preoperative 18f fdg pet ct followed curative surgical resection participant age sex eastern cooperative oncology group performance status score baseline serum ca 19 9 level stage pathologic n stages tumor size tumor grade tumor growth pattern r0 resection adjuvant therapy included clinicopathological variables predicting overall survival pet variables maximum standardized uptake value suvmax average suv suvavg metabolic tumor volume mtv total lesion glycolysis tlg tumor kaplan meyer method cox proportional hazards model used survival analysis results total 15 40 patients 37 5 died follow period univariate analysis low suvmax 2 7 p 0 0005 low suvavg 2 6 p 0 0034 significant predictors poor overall survival multivariate analyses low suvmax hr 6 7016 95 ci 1 9961 22 4993 p 0 0047 independent prognostic factor associated poor overall survival conclusion suvmax primary tumor measured 18f fdg pet ct independent significant prognostic factor overall survival patients distal bile duct cancer however different results previous study warrant large sample sized study stn","probabilities":0.9799733,"Title":"Prognostic Significance Of 18F-Fdg Pet/Ct In Patients With Distal Bile Duct Cancer Undergoing Curative Surgery","Abstract":"Purpose: As there were few previous studies with a small number of subjects, the purpose of this was to evaluate the prognostic significance of 18F-FDG PET/CT in patients with distal bile duct cancer undergoing curative surgery. \r\n\r\n Methods: The study included 40 patients (M/F = 24:16; age 68.0 ± 8.0 years) who underwent preoperative 18F-FDG PET/CT followed by curative surgical resection. The participant's age, sex, Eastern Cooperative Oncology Group performance-status score, baseline serum CA 19-9 level, stage, pathologic T and N stages, tumor size, tumor grade, tumor growth pattern, R0 resection, and adjuvant therapy were included as clinicopathological variables for predicting overall survival. The PET variables were maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the tumor. The Kaplan-Meyer method and Cox proportional hazards model were used for the survival analysis. \r\n\r\n Results: A total of 15 of 40 patients (37.5%) died during the follow-up period. In univariate analysis, low SUVmax (≤ 2.7, p = 0.0005) and low SUVavg (≤ 2.6, p = 0.0034) were significant predictors of poor overall survival. In multivariate analyses, only low SUVmax (HR = 6.7016, 95% CI 1.9961-22.4993, p = 0.0047) was an independent prognostic factor associated with poor overall survival. \r\n\r\n Conclusion: The SUVmax of the primary tumor measured by 18F-FDG PET/CT was an independent significant prognostic factor for overall survival in patients with distal bile duct cancer. However, different results from a previous study warrant further large sample-sized study.","Source":"STN","category":"HUMAN","training_data":"Prognostic Significance Of 18F-Fdg Pet/Ct In Patients With Distal Bile Duct Cancer Undergoing Curative Surgery Purpose: As there were few previous studies with a small number of subjects, the purpose of this was to evaluate the prognostic significance of 18F-FDG PET/CT in patients with distal bile duct cancer undergoing curative surgery. \r\n\r\n Methods: The study included 40 patients (M/F = 24:16; age 68.0 ± 8.0 years) who underwent preoperative 18F-FDG PET/CT followed by curative surgical resection. The participant's age, sex, Eastern Cooperative Oncology Group performance-status score, baseline serum CA 19-9 level, stage, pathologic T and N stages, tumor size, tumor grade, tumor growth pattern, R0 resection, and adjuvant therapy were included as clinicopathological variables for predicting overall survival. The PET variables were maximum standardized uptake value (SUVmax), average SUV (SUVavg), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the tumor. The Kaplan-Meyer method and Cox proportional hazards model were used for the survival analysis. \r\n\r\n Results: A total of 15 of 40 patients (37.5%) died during the follow-up period. In univariate analysis, low SUVmax (≤ 2.7, p = 0.0005) and low SUVavg (≤ 2.6, p = 0.0034) were significant predictors of poor overall survival. In multivariate analyses, only low SUVmax (HR = 6.7016, 95% CI 1.9961-22.4993, p = 0.0047) was an independent prognostic factor associated with poor overall survival. \r\n\r\n Conclusion: The SUVmax of the primary tumor measured by 18F-FDG PET/CT was an independent significant prognostic factor for overall survival in patients with distal bile duct cancer. However, different results from a previous study warrant further large sample-sized study. STN","prediction_labels":"HUMAN"},{"cleaned":"clinicopathologic prognostic features gallbladder malignancies retrospective analysis 5206 cases safra kesesi malignitelerinde klinikopatolojik ve prognostik ozellikler 5206 olgunun retrospektif olarak incelenmesi aim gallbladder cancer sixth common cancer gastrointestinal system clinical presentation may distinguished cholelithiasis cholecystitis patients diagnosed intraoperatively postoperative histologic examination study aimed investigate association incidentally detected gallbladder cancer gallbladder premalignant lesions age gender ultrasonography features gallbladder stones methods demographic clinical characteristics pathology results 5206 patients underwent cholecystectomy january 2012 december 2015 evaluated retrospectively results three thousand eight hundred eighty four 74 6 patients female pathologic reports showed pre malignant malignant lesions 102 1 95 cases metaplasia significantly common females significant difference found development dysplasia cancer genders gallbladder stone found risk factor development metaplasia gallbladder wall thickening advanced age important risk factors gallbladder cancer conclusion female gender gallstone important risk factors development metaplasia advanced age gallstone gallbladder wall thickening ultrasonography important factors development cancer cholecystectomy kept mind effective method prevent cancer development elderly patients gallbladder stones google scholar","probabilities":0.9799733,"Title":"Clinicopathologic And Prognostic Features In Gallbladder Malignancies: Retrospective Analysis Of 5206 Cases Safra Kesesi Malignitelerinde Klinikopatolojik Ve Prognostik Ozellikler: 5206 Olgunun Retrospektif Olarak Incelenmesi","Abstract":"Aim: Gallbladder cancer is the sixth most common cancer of the gastrointestinal system. Clinical presentation may not be distinguished from cholelithiasis or cholecystitis and most patients are diagnosed intraoperatively or in the postoperative histologic examination. In this study, we aimed to investigate the association of incidentally detected gallbladder cancer with gallbladder premalignant lesions, age, gender, ultrasonography features and gallbladder stones. Methods: Demographic and clinical characteristics and pathology results of 5206 patients who underwent cholecystectomy between January 2012 and December 2015 were evaluated retrospectively. Results: Three thousand eight hundred and eighty four (74.6%) patients were female. Pathologic reports showed pre-malignant and malignant lesions in 102 (1.95%) cases. Metaplasia was significantly more common in females, while no significant difference was found in development of dysplasia and cancer between genders. Gallbladder stone was found to be a risk factor for the development of metaplasia. Gallbladder wall thickening and advanced age are the most important risk factors for gallbladder cancer. Conclusion: Female gender and gallstone are important risk factors for the development of metaplasia. Advanced age, gallstone and gallbladder wall thickening on ultrasonography are the most important factors in the development cancer. Cholecystectomy should be kept in mind as the most effective method to prevent cancer development in elderly patients with gallbladder stones.","Source":"Google Scholar","category":"HUMAN","training_data":"Clinicopathologic And Prognostic Features In Gallbladder Malignancies: Retrospective Analysis Of 5206 Cases Safra Kesesi Malignitelerinde Klinikopatolojik Ve Prognostik Ozellikler: 5206 Olgunun Retrospektif Olarak Incelenmesi Aim: Gallbladder cancer is the sixth most common cancer of the gastrointestinal system. Clinical presentation may not be distinguished from cholelithiasis or cholecystitis and most patients are diagnosed intraoperatively or in the postoperative histologic examination. In this study, we aimed to investigate the association of incidentally detected gallbladder cancer with gallbladder premalignant lesions, age, gender, ultrasonography features and gallbladder stones. Methods: Demographic and clinical characteristics and pathology results of 5206 patients who underwent cholecystectomy between January 2012 and December 2015 were evaluated retrospectively. Results: Three thousand eight hundred and eighty four (74.6%) patients were female. Pathologic reports showed pre-malignant and malignant lesions in 102 (1.95%) cases. Metaplasia was significantly more common in females, while no significant difference was found in development of dysplasia and cancer between genders. Gallbladder stone was found to be a risk factor for the development of metaplasia. Gallbladder wall thickening and advanced age are the most important risk factors for gallbladder cancer. Conclusion: Female gender and gallstone are important risk factors for the development of metaplasia. Advanced age, gallstone and gallbladder wall thickening on ultrasonography are the most important factors in the development cancer. Cholecystectomy should be kept in mind as the most effective method to prevent cancer development in elderly patients with gallbladder stones. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"tea consumption risk biliary tract cancer systematic review dose response meta analysis observational studies recent studies shown tea consumption associated reduced incidence types cancer possibly including biliary tract cancer however epidemiological evidences association risk biliary tract cancer contradictory thus performed meta analysis published observational studies assess association tea consumption risk biliary tract cancer relevant studies identified searching pubmed embase isi web science published october 2016 newcastle ottawa scale used evaluate quality included studies publication bias evaluated using funnel plots begg egger tests meta analysis includes eight studies comprising 18 independent reports incidence biliary tract cancer reduced 34 significantly tea intake group comparison never intake group summary odds ratio 0 66 95 confidence interval ci 0 48 0 85 additionally inverse relationship tea intake risk biliary tract cancer statistically significant women 0 65 95 ci 0 47 0 83 men 0 86 95 ci 0 58 1 13 dose response analysis indicated risk biliary tract cancer decreased 4 additional cup tea one day relative risk rr 0 96 95 ci 0 93 0 98 p 0 001 summary tea intake associated decreased risk biliary tract cancer especially women pubmed","probabilities":0.9799733,"Title":"Tea consumption and the risk of biliary tract cancer: a systematic review and dose-response meta-analysis of observational studies","Abstract":"Recent studies have shown that tea consumption is associated with the reduced incidence of some types of cancer, possibly including biliary tract cancer. However, the epidemiological evidences for the association with risk of biliary tract cancer are contradictory. Thus, we performed meta-analysis of published observational studies to assess the association between tea consumption and risk of biliary tract cancer. Relevant studies were identified by searching PubMed, EMBASE, and ISI Web of Science published before October 2016. The Newcastle-Ottawa Scale was used to evaluate the quality of included studies, and publication bias was evaluated using funnel plots, and Begg's and Egger's tests. This meta-analysis includes eight studies comprising 18 independent reports. The incidence of biliary tract cancer reduced about 34% (significantly) for tea intake group in comparison with never intake group (summary odds ratio [OR] = 0.66; 95% confidence interval [CI] = 0.48-0.85). Additionally, an inverse relationship between tea intake and risk of biliary tract cancer was statistically significant in women (OR = 0.65; 95 % CI = 0.47-0.83), but not in men (OR = 0.86; 95% CI = 0.58-1.13). Dose- response analysis indicated that the risk of biliary tract cancer decreased by 4% with each additional cup of tea one day (relative risk [RR] = 0.96, 95% CI = 0.93-0.98, p = 0.001). In summary, tea intake is associated with decreased risk of biliary tract cancer, especially for women.","Source":"PubMed","category":"HUMAN","training_data":"Tea consumption and the risk of biliary tract cancer: a systematic review and dose-response meta-analysis of observational studies Recent studies have shown that tea consumption is associated with the reduced incidence of some types of cancer, possibly including biliary tract cancer. However, the epidemiological evidences for the association with risk of biliary tract cancer are contradictory. Thus, we performed meta-analysis of published observational studies to assess the association between tea consumption and risk of biliary tract cancer. Relevant studies were identified by searching PubMed, EMBASE, and ISI Web of Science published before October 2016. The Newcastle-Ottawa Scale was used to evaluate the quality of included studies, and publication bias was evaluated using funnel plots, and Begg's and Egger's tests. This meta-analysis includes eight studies comprising 18 independent reports. The incidence of biliary tract cancer reduced about 34% (significantly) for tea intake group in comparison with never intake group (summary odds ratio [OR] = 0.66; 95% confidence interval [CI] = 0.48-0.85). Additionally, an inverse relationship between tea intake and risk of biliary tract cancer was statistically significant in women (OR = 0.65; 95 % CI = 0.47-0.83), but not in men (OR = 0.86; 95% CI = 0.58-1.13). Dose- response analysis indicated that the risk of biliary tract cancer decreased by 4% with each additional cup of tea one day (relative risk [RR] = 0.96, 95% CI = 0.93-0.98, p = 0.001). In summary, tea intake is associated with decreased risk of biliary tract cancer, especially for women. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiology surgical management intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc rare hepatobiliary malignancy arising epithelial cells intrahepatic bile ducts increased incidence icc worldwide may reflect true increase earlier detection disease despite advances modern surgical care curative chance icc remained suboptimal tumor free margins hard achieve due tumor locations technical challenges recurrence either local distant may hamper resectability large number patients lymph node involvement vascular invasions considered negative predictive factors survival icc patients review discusses epidemiology risk factors surgical management iccs mainly focuses outcomes factors associated surgical treatment google scholar","probabilities":0.9799733,"Title":"Epidemiology And Surgical Management Of Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary malignancy arising from the epithelial cells of the intrahepatic bile ducts. The increased incidence of ICC worldwide may reflect both a true increase and the earlier detection of the disease. Despite the advances in modern surgical care, the curative chance for ICC remained suboptimal: tumor-free margins are hard to achieve due to tumor locations, and technical challenges and recurrence, either local or distant, may hamper the resectability in a large number of patients. Lymph node involvement and vascular invasions are considered negative predictive factors for survival of ICC patients. This review discusses the epidemiology, risk factors and surgical management of ICCs, and mainly focuses on outcomes and factors associated with surgical treatment.","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology And Surgical Management Of Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is a rare hepatobiliary malignancy arising from the epithelial cells of the intrahepatic bile ducts. The increased incidence of ICC worldwide may reflect both a true increase and the earlier detection of the disease. Despite the advances in modern surgical care, the curative chance for ICC remained suboptimal: tumor-free margins are hard to achieve due to tumor locations, and technical challenges and recurrence, either local or distant, may hamper the resectability in a large number of patients. Lymph node involvement and vascular invasions are considered negative predictive factors for survival of ICC patients. This review discusses the epidemiology, risk factors and surgical management of ICCs, and mainly focuses on outcomes and factors associated with surgical treatment. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"treatment gallbladder cancer results 1037 cases german registry incidental gallbladder carcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Treatment Of Gallbladder Cancer- Results Of 1037 Cases Of «The German- Registry» Of Incidental Gallbladder Carcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Treatment Of Gallbladder Cancer- Results Of 1037 Cases Of «The German- Registry» Of Incidental Gallbladder Carcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"curious case cholangiocarcinoma opportunities environmental health scientists learn complex disease deaths complex noncommunicable diseases cancer predicted continue increase worldwide low middle income countries bearing brunt burden problem requires concentrated global effort avoid devastating losses life well economic losses cholangiocarcinoma cca readily studied model complex noncommunicable disease receives little attention outside scientific community southeast asia bring attention opportunity study cca model understand role multiple complex factors cancer factors include allostatic load individual genetic susceptibility environmental exposures chemicals diet socioeconomic factors psychosocial stress study cca offers unique opportunity make novel observations advance progress prevention intervention approaches prevalent diseases involve complex multifactorial interactions pubmed","probabilities":0.9799733,"Title":"The Curious Case of Cholangiocarcinoma: Opportunities for Environmental Health Scientists to Learn about a Complex Disease","Abstract":"Deaths from complex, noncommunicable diseases such as cancer are predicted to continue to increase worldwide, with low- and middle-income countries bearing the brunt of the burden. This problem requires a concentrated global effort to avoid devastating losses of life as well as economic losses. Cholangiocarcinoma (CCA) is a readily studied model of complex, noncommunicable disease, but it receives little attention outside of the scientific community in Southeast Asia. Here, we bring attention to the opportunity to study CCA as a model to understand the role of multiple, complex factors in cancer. These factors include allostatic load, individual genetic susceptibility, and environmental exposures such as chemicals, diet, socioeconomic factors, and psychosocial stress. The study of CCA offers a unique opportunity to make novel observations that could advance progress in prevention and intervention approaches for prevalent diseases that involve complex, multifactorial interactions.","Source":"PubMed","category":"HUMAN","training_data":"The Curious Case of Cholangiocarcinoma: Opportunities for Environmental Health Scientists to Learn about a Complex Disease Deaths from complex, noncommunicable diseases such as cancer are predicted to continue to increase worldwide, with low- and middle-income countries bearing the brunt of the burden. This problem requires a concentrated global effort to avoid devastating losses of life as well as economic losses. Cholangiocarcinoma (CCA) is a readily studied model of complex, noncommunicable disease, but it receives little attention outside of the scientific community in Southeast Asia. Here, we bring attention to the opportunity to study CCA as a model to understand the role of multiple, complex factors in cancer. These factors include allostatic load, individual genetic susceptibility, and environmental exposures such as chemicals, diet, socioeconomic factors, and psychosocial stress. The study of CCA offers a unique opportunity to make novel observations that could advance progress in prevention and intervention approaches for prevalent diseases that involve complex, multifactorial interactions. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extracapsular lymph node spread negative prognostic factor adenocarcinoma pancreas cancer papilla vater objective aim study analyze incidence impact extracapsular lymph node spread elns pancreatic cancer pc cancer papilla vater cpv methods 2004 2009 148 patients underwent surgical therapy pc n 112 cpv n 36 resected lymph nodes lns analyzed elns results 95 64 2 patients ln metastasis present 45 47 3 patients elns present histopathology patients survival negatively affected elns pc 5 year survival rate 37 patients ln metastasis compared 4 0 patients ln metastasis pn1 without extracapsular ln involvement patients pn1 disease extracapsular ln involvement least 1 ln respectively p 0 001 patients cpv 5 year survival rate 56 patients ln metastasis 44 0 patients pn1 disease without extracapsular ln involvement patients pn1 disease extracapsular ln involvement least 1 ln respectively p 0 006 multivariate analysis revealed elns independent prognostic factor survival tumor types conclusions extracapsular ln spread independent negative prognostic factor pc cpv future staging systems elns included pubmed","probabilities":0.9799733,"Title":"Extracapsular lymph node spread as a negative prognostic factor of adenocarcinoma of the pancreas and cancer of the papilla of vater","Abstract":"OBJECTIVE: The aim of this study was to analyze the incidence and impact of extracapsular lymph node spread (ELNS) in pancreatic cancer (PC) and cancer of the papilla of Vater (CPV). METHODS: Between 2004 and 2009, 148 patients underwent surgical therapy for PC (n = 112) and CPV (n = 36). The resected lymph nodes (LNs) were further analyzed for ELNS. RESULTS: In 95 (64.2%) patients, LN metastasis was present. In 45 (47.3%) of these patients, an ELNS was present on histopathology. The patients' survival was negatively affected by ELNS. For PC, the 5-year survival rate was 37% for patients with no LN metastasis compared with 4% and 0% for patients with LN metastasis (pN1) but without extracapsular LN involvement and patients with pN1 disease with extracapsular LN involvement of at least 1 LN, respectively (P < 0.001). In patients with CPV, the 5-year survival rate was 56% for patients with no LN metastasis and 44% and 0% for patients with pN1 disease but without extracapsular LN involvement and patients with pN1 disease with extracapsular LN involvement of at least 1 LN, respectively (P = 0.006). Multivariate analysis revealed ELNS as an independent prognostic factor of survival for both tumor types. CONCLUSIONS: Extracapsular LN spread is an independent negative prognostic factor in PC and CPV. In future staging systems, ELNS should be included.","Source":"PubMed","category":"HUMAN","training_data":"Extracapsular lymph node spread as a negative prognostic factor of adenocarcinoma of the pancreas and cancer of the papilla of vater OBJECTIVE: The aim of this study was to analyze the incidence and impact of extracapsular lymph node spread (ELNS) in pancreatic cancer (PC) and cancer of the papilla of Vater (CPV). METHODS: Between 2004 and 2009, 148 patients underwent surgical therapy for PC (n = 112) and CPV (n = 36). The resected lymph nodes (LNs) were further analyzed for ELNS. RESULTS: In 95 (64.2%) patients, LN metastasis was present. In 45 (47.3%) of these patients, an ELNS was present on histopathology. The patients' survival was negatively affected by ELNS. For PC, the 5-year survival rate was 37% for patients with no LN metastasis compared with 4% and 0% for patients with LN metastasis (pN1) but without extracapsular LN involvement and patients with pN1 disease with extracapsular LN involvement of at least 1 LN, respectively (P < 0.001). In patients with CPV, the 5-year survival rate was 56% for patients with no LN metastasis and 44% and 0% for patients with pN1 disease but without extracapsular LN involvement and patients with pN1 disease with extracapsular LN involvement of at least 1 LN, respectively (P = 0.006). Multivariate analysis revealed ELNS as an independent prognostic factor of survival for both tumor types. CONCLUSIONS: Extracapsular LN spread is an independent negative prognostic factor in PC and CPV. In future staging systems, ELNS should be included. PubMed","prediction_labels":"HUMAN"},{"cleaned":"patterns distribution hepatic nodules single satellites multifocal intrahepatic cholangiocarcinoma prognostic impact surgery objective aimed compare clinicopathological features survival surgery patients intrahepatic cholangiocarcinoma icc according patterns distribution hepatic nodules methods retrospective analysis multi institutional series 259 patients resected icc carried patients classified according pattern distribution hepatic nodules single tumors type single tumors satellites liver segment type ii multifocal tumors type iii results overall 64 5 patients type 21 9 type ii 13 5 type iii 5 year overall survival rate 49 4 34 2 9 9 types ii iii respectively p 0 001 multivariate survival analysis identified following independent prognostic factors pattern types ii iii p 0 001 p 0 001 respectively size 50 mm p 0 021 lymph node ln metastases p 0 005 r1 resections p 0 019 stratified survival type pattern according prognostic factors identified multivariate analysis n0 r0 patients type ii iii tumors encouraging long term results conversely patients ln metastases r1 resections poor prognosis particularly patients type iii tumors conclusion icc distinct patterns distribution different prognoses considered making therapeutic decisions patients type iii tumors significantly worse prognosis benefits upfront surgery carefully evaluated stn","probabilities":0.9799733,"Title":"Patterns Of Distribution Of Hepatic Nodules (Single Satellites Or Multifocal) In Intrahepatic Cholangiocarcinoma: Prognostic Impact After Surgery","Abstract":"Objective: We aimed to compare the clinicopathological features and survival after surgery of patients with intrahepatic cholangiocarcinoma (ICC) according to the patterns of distribution of hepatic nodules. \r\n\r\n Methods: A retrospective analysis of a multi-institutional series of 259 patients with resected ICC was carried out. Patients were further classified according to the pattern of distribution of hepatic nodules: single tumors (type I), single tumors with satellites in the same liver segment (type II), or multifocal tumors (type III). \r\n\r\n Results: Overall, 64.5% of patients had type I, 21.9% had type II, and 13.5% had type III. The 5-year overall survival rate was 49.4, 34.2, and 9.9% for types I, II, and III, respectively (p < 0.001). A multivariate survival analysis identified the following independent prognostic factors: pattern types II and III (p = 0.001 and p = 0.001, respectively), size ≥ 50 mm (p = 0.021), lymph node (LN) metastases (p = 0.005), and R1 resections (p = 0.019). We stratified survival for each type of pattern according to the other prognostic factors identified in the multivariate analysis. N0 and R0 patients with type II and III tumors had encouraging long-term results. Conversely, patients with LN metastases and R1 resections had poor prognosis, particularly patients with type III tumors. \r\n\r\n Conclusion: ICC has distinct patterns of distribution with different prognoses that should be considered when making therapeutic decisions. Patients with type III tumors had a significantly worse prognosis, and the benefits of upfront surgery should be carefully evaluated.","Source":"STN","category":"HUMAN","training_data":"Patterns Of Distribution Of Hepatic Nodules (Single Satellites Or Multifocal) In Intrahepatic Cholangiocarcinoma: Prognostic Impact After Surgery Objective: We aimed to compare the clinicopathological features and survival after surgery of patients with intrahepatic cholangiocarcinoma (ICC) according to the patterns of distribution of hepatic nodules. \r\n\r\n Methods: A retrospective analysis of a multi-institutional series of 259 patients with resected ICC was carried out. Patients were further classified according to the pattern of distribution of hepatic nodules: single tumors (type I), single tumors with satellites in the same liver segment (type II), or multifocal tumors (type III). \r\n\r\n Results: Overall, 64.5% of patients had type I, 21.9% had type II, and 13.5% had type III. The 5-year overall survival rate was 49.4, 34.2, and 9.9% for types I, II, and III, respectively (p < 0.001). A multivariate survival analysis identified the following independent prognostic factors: pattern types II and III (p = 0.001 and p = 0.001, respectively), size ≥ 50 mm (p = 0.021), lymph node (LN) metastases (p = 0.005), and R1 resections (p = 0.019). We stratified survival for each type of pattern according to the other prognostic factors identified in the multivariate analysis. N0 and R0 patients with type II and III tumors had encouraging long-term results. Conversely, patients with LN metastases and R1 resections had poor prognosis, particularly patients with type III tumors. \r\n\r\n Conclusion: ICC has distinct patterns of distribution with different prognoses that should be considered when making therapeutic decisions. Patients with type III tumors had a significantly worse prognosis, and the benefits of upfront surgery should be carefully evaluated. STN","prediction_labels":"HUMAN"},{"cleaned":"invasion hepatic artery crucial predictor poor outcomes gallbladder carcinoma background present study undertook retrospective analysis gallbladder carcinoma assess whether histologically determined hepatic artery ha invasion portal vein pv invasion considered prognostic factors methods seventy one patients undergone radical resection gallbladder carcinoma 1995 2008 university tsukuba selected database analysis patients required extended surgery para aortic lymph node metastasis also included correlation invasion ha pv prognosis clinicopathologic factors analyzed results two postoperative deaths among 71 patients pathological invasion ha confirmed 16 22 5 cases pv invasion confirmed 15 patients patients invasion ha significantly poorer prognosis without ha invasion p 0 0001 additionally univariate analysis gender male positive para aortic lymph node metastasis pv invasion ha invasion identified significant poor prognostic factors multivariate analysis ha invasion independent prognostic factor odds ratio 0 323 p 0 029 conclusions invasion ha crucial prognostic factor patients gallbladder carcinoma stn","probabilities":0.9799733,"Title":"Invasion Of The Hepatic Artery Is A Crucial Predictor Of Poor Outcomes In Gallbladder Carcinoma","Abstract":"Background: In the present study we undertook a retrospective analysis of gallbladder carcinoma to assess whether histologically determined hepatic artery (HA) invasion and portal vein (PV) invasion can be considered prognostic factors. \n\n Methods: Seventy-one patients who had undergone radical resection for gallbladder carcinoma between 1995 and 2008 at University of Tsukuba were selected from the database for analysis. Patients who required extended surgery for para-aortic lymph node metastasis were also included. Correlation between invasion of the HA and the PV and prognosis and other clinicopathologic factors were analyzed. \n\n Results: There were two postoperative deaths among the 71 patients. Pathological invasion of the HA was confirmed in 16 (22.5%) cases and PV invasion was confirmed in 15 patients. Patients with invasion of the HA had a significantly poorer prognosis than those without HA invasion (P < 0.0001). Additionally, in univariate analysis, gender (male), positive para-aortic lymph node metastasis, PV invasion, and HA invasion were identified as significant poor prognostic factors. In multivariate analysis, only HA invasion was an independent prognostic factor (Odds Ratio 0.323; P = 0.029). \n\n Conclusions: Invasion of the HA is a crucial prognostic factor in patients with gallbladder carcinoma.","Source":"STN","category":"HUMAN","training_data":"Invasion Of The Hepatic Artery Is A Crucial Predictor Of Poor Outcomes In Gallbladder Carcinoma Background: In the present study we undertook a retrospective analysis of gallbladder carcinoma to assess whether histologically determined hepatic artery (HA) invasion and portal vein (PV) invasion can be considered prognostic factors. \n\n Methods: Seventy-one patients who had undergone radical resection for gallbladder carcinoma between 1995 and 2008 at University of Tsukuba were selected from the database for analysis. Patients who required extended surgery for para-aortic lymph node metastasis were also included. Correlation between invasion of the HA and the PV and prognosis and other clinicopathologic factors were analyzed. \n\n Results: There were two postoperative deaths among the 71 patients. Pathological invasion of the HA was confirmed in 16 (22.5%) cases and PV invasion was confirmed in 15 patients. Patients with invasion of the HA had a significantly poorer prognosis than those without HA invasion (P < 0.0001). Additionally, in univariate analysis, gender (male), positive para-aortic lymph node metastasis, PV invasion, and HA invasion were identified as significant poor prognostic factors. In multivariate analysis, only HA invasion was an independent prognostic factor (Odds Ratio 0.323; P = 0.029). \n\n Conclusions: Invasion of the HA is a crucial prognostic factor in patients with gallbladder carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"vivo monitoring development cholangiocarcinoma induced c objectives purpose study evaluate high resolution ultrasound magnetic resonance imaging mri monitoring cholangiocarcinoma hamsters c sinensis infection n nitrosodimethylamine ndma materials methods twenty four male syrian golden hamsters divided four groups composed five hamsters control five hamsters receiving 30 metacercariae c sinensis per hamster five hamsters receiving ndma drinking water nine hamsters receiving metacercariae ndma ultrasound performed every week baseline 12th week infection mri histopathologic examination done 4th week 12th week results cholangiocarcinomas appeared early 6th week infection 12 cholangiocarcinomas nine ten demonstrated ultrasound mri respectively ultrasound mri findings cholangiocarcinomas hamsters similar mass forming intrahepatic cholangiocarcinomas humans ultrasound mri also showed findings disease progression periductal increased echogenicity signal intensity ductal dilatation complicated cysts sludges gallbladder conclusions high resolution ultrasound mri monitor detect occurrence cholangiocarcinoma hamsters non invasively key points high resolution ultrasound mri monitor occurrence cholangiocarcinoma hamsters cholangiocarcinomas detected early 6th week c sinensis infection axial t2 weighted mri demonstrated cholangiocarcinomas various inflammatory findings hamsters stn","probabilities":0.9799733,"Title":"In-Vivo Monitoring Of Development Of Cholangiocarcinoma Induced With C","Abstract":"Objectives: The purpose of this study is to evaluate high-resolution ultrasound and magnetic resonance imaging (MRI) in monitoring of cholangiocarcinoma in the hamsters with C. sinensis infection and N-nitrosodimethylamine (NDMA). \r\n\r\n Materials and methods: Twenty-four male Syrian golden hamsters of were divided into four groups composed of five hamsters as control, five hamsters receiving 30 metacercariae of C. sinensis per each hamster, five hamsters receiving NDMA in drinking water, and nine hamsters receiving both metacercariae and NDMA. Ultrasound was performed every other week from baseline to the 12th week of infection. MRI and histopathologic examination was done from the 4th week to 12th week. \r\n\r\n Results: Cholangiocarcinomas appeared as early as the 6th week of infection. There were 12 cholangiocarcinomas, nine and ten of which were demonstrated by ultrasound and MRI, respectively. Ultrasound and MRI findings of cholangiocarcinomas in the hamsters were similar to those of the mass-forming intrahepatic cholangiocarcinomas in humans. Ultrasound and MRI also showed other findings of disease progression such as periductal increased echogenicity or signal intensity, ductal dilatation, complicated cysts, and sludges in the gallbladder. \r\n\r\n Conclusions: High-resolution ultrasound and MRI can monitor and detect the occurrence of cholangiocarcinoma in the hamsters non-invasively. \r\n\r\n Key points: • High-resolution ultrasound and MRI can monitor occurrence of cholangiocarcinoma in the hamsters. • Cholangiocarcinomas were detected as early as the 6th week after C. sinensis infection. • Axial T2-weighted MRI demonstrated cholangiocarcinomas and various inflammatory findings in the hamsters.","Source":"STN","category":"ANIMAL","training_data":"In-Vivo Monitoring Of Development Of Cholangiocarcinoma Induced With C Objectives: The purpose of this study is to evaluate high-resolution ultrasound and magnetic resonance imaging (MRI) in monitoring of cholangiocarcinoma in the hamsters with C. sinensis infection and N-nitrosodimethylamine (NDMA). \r\n\r\n Materials and methods: Twenty-four male Syrian golden hamsters of were divided into four groups composed of five hamsters as control, five hamsters receiving 30 metacercariae of C. sinensis per each hamster, five hamsters receiving NDMA in drinking water, and nine hamsters receiving both metacercariae and NDMA. Ultrasound was performed every other week from baseline to the 12th week of infection. MRI and histopathologic examination was done from the 4th week to 12th week. \r\n\r\n Results: Cholangiocarcinomas appeared as early as the 6th week of infection. There were 12 cholangiocarcinomas, nine and ten of which were demonstrated by ultrasound and MRI, respectively. Ultrasound and MRI findings of cholangiocarcinomas in the hamsters were similar to those of the mass-forming intrahepatic cholangiocarcinomas in humans. Ultrasound and MRI also showed other findings of disease progression such as periductal increased echogenicity or signal intensity, ductal dilatation, complicated cysts, and sludges in the gallbladder. \r\n\r\n Conclusions: High-resolution ultrasound and MRI can monitor and detect the occurrence of cholangiocarcinoma in the hamsters non-invasively. \r\n\r\n Key points: • High-resolution ultrasound and MRI can monitor occurrence of cholangiocarcinoma in the hamsters. • Cholangiocarcinomas were detected as early as the 6th week after C. sinensis infection. • Axial T2-weighted MRI demonstrated cholangiocarcinomas and various inflammatory findings in the hamsters. STN","prediction_labels":"HUMAN"},{"cleaned":"major postoperative complications compromise oncological outcomes patients intrahepatic cholangiocarcinoma curative resection 13 year cohort tertiary center background objective hepatectomy mainstay curative treatment intrahepatic cholangiocarcinoma icc relationship postoperative complication oncological outcome defined aimed elucidate effect postoperative complication long term survival icc patients curative resection methods data consecutive patients curative resection icc hospital 1991 2013 reviewed patients cholangiohepatocellular carcinoma metastatic adenocarcinoma klaskin tumor excluded clinicopathological data postoperative events extracted database survival analysis results 107 patients series median age 61 years median follow time 24 months median tumor size 6 cm major hepatectomy required 52 3 median operation time blood loss 439 minutes 0 9l respectively r0 resection achieved 88 8 median length stay 11 days 30 day 90 day mortality 2 5 6 8 respectively major complications found 20 6 patients postoperative complications significantly inferior survival patients without 3 yr dfs 38 vs 27 p 0 001 3 yr overall 51 vs 27 p 0 001 multivariable analysis showed postoperative complication independent factor associated disease free survival 1 9 95 c 1 10 3 24 p 0 021 overall survival 2 1 95 c 1 13 3 93 p 0 018 conclusion postoperative complication significant impact icc patients long term survival extra measures adjuvant chemotherapy considered patients develop major complications surgery pubmed","probabilities":0.9799733,"Title":"Major postoperative complications compromise oncological outcomes of patients with intrahepatic cholangiocarcinoma after curative resection - A 13-year cohort in a tertiary center","Abstract":"BACKGROUND/OBJECTIVE: Hepatectomy is the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). The relationship between postoperative complication and oncological outcome has not been defined. We aimed to elucidate the effect of postoperative complication on long-term survival of ICC patients after curative resection. METHODS: Data of consecutive patients who had curative resection for ICC at our hospital from 1991 to 2013 were reviewed. Patients with cholangiohepatocellular carcinoma, metastatic adenocarcinoma or Klaskin tumor were excluded. Clinicopathological data and postoperative events were extracted from database for survival analysis. RESULTS: There were 107 patients in our series. Their median age was 61 years. The median follow-up time was 24 months. The median tumor size was 6 cm. Major hepatectomy was required in 52.3% of them. The median operation time and blood loss was 439 minutes and 0.9L respectively. R0 resection was achieved in 88.8% of them. The median length of stay was 11 days. The 30-day and 90-day mortality was 2.5% and 6.8% respectively. Major complications were found in 20.6% of them. Patients with postoperative complications had significantly inferior survival than patients without (3-yr DFS 38% vs. 27%, P = 0.001; 3-yr overall: 51% vs. 27%, P < 0.001). Multivariable analysis showed that postoperative complication was an independent factor associated with disease-free survival (OR 1.9 95% C.I. 1.10-3.24, P = 0.021) and overall survival (OR 2.1, 95% C.I. 1.13-3.93, P = 0.018). CONCLUSION: Postoperative complication has a significant impact on ICC patients' long-term survival. Extra measures such as adjuvant chemotherapy should be considered for patients who develop major complications after surgery.","Source":"PubMed","category":"HUMAN","training_data":"Major postoperative complications compromise oncological outcomes of patients with intrahepatic cholangiocarcinoma after curative resection - A 13-year cohort in a tertiary center BACKGROUND/OBJECTIVE: Hepatectomy is the mainstay of curative treatment for intrahepatic cholangiocarcinoma (ICC). The relationship between postoperative complication and oncological outcome has not been defined. We aimed to elucidate the effect of postoperative complication on long-term survival of ICC patients after curative resection. METHODS: Data of consecutive patients who had curative resection for ICC at our hospital from 1991 to 2013 were reviewed. Patients with cholangiohepatocellular carcinoma, metastatic adenocarcinoma or Klaskin tumor were excluded. Clinicopathological data and postoperative events were extracted from database for survival analysis. RESULTS: There were 107 patients in our series. Their median age was 61 years. The median follow-up time was 24 months. The median tumor size was 6 cm. Major hepatectomy was required in 52.3% of them. The median operation time and blood loss was 439 minutes and 0.9L respectively. R0 resection was achieved in 88.8% of them. The median length of stay was 11 days. The 30-day and 90-day mortality was 2.5% and 6.8% respectively. Major complications were found in 20.6% of them. Patients with postoperative complications had significantly inferior survival than patients without (3-yr DFS 38% vs. 27%, P = 0.001; 3-yr overall: 51% vs. 27%, P < 0.001). Multivariable analysis showed that postoperative complication was an independent factor associated with disease-free survival (OR 1.9 95% C.I. 1.10-3.24, P = 0.021) and overall survival (OR 2.1, 95% C.I. 1.13-3.93, P = 0.018). CONCLUSION: Postoperative complication has a significant impact on ICC patients' long-term survival. Extra measures such as adjuvant chemotherapy should be considered for patients who develop major complications after surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prospective association liver function biomarkers development hepatobiliary cancers introduction serum liver biomarkers gamma glutamyl transferase ggt alanine aminotransferase alt aspartate aminotransferase ast alkaline phosphatase alp total bilirubin used indicators liver disease currently little data prospective association risk hepatobiliary cancers methods nested case control study conducted within prospective epic cohort 520 000 participants 10 european countries mean 7 5 mean years follow 121 hepatocellular carcinoma hcc 34 intrahepatic bile duct ihbc 131 gallbladder biliary tract gbtc cases identified matched 2 controls circulating biomarkers measured serum taken recruitment cohort prior cancer diagnosis multivariable adjusted conditional logistic regression used calculate odds ratios 95 confidence intervals 95 ci results multivariable models 1sd increase log transformed biomarker positively associated hcc risk ggt 4 23 95 ci 2 72 6 59 alp 3 43 95 ci 2 31 5 10 ast 3 00 95 ci 2 04 4 42 alt 2 69 95 ci 1 89 3 84 bilirubin 2 25 95 ci 1 58 3 20 liver enzyme ggt 4 98 95 ci 1 75 14 17 ast 3 10 95 ci 1 04 9 30 alt 2 86 95 ci 1 26 6 48 alp 2 31 95 ci 1 10 4 86 bilirubin bilirubin 1 46 95 ci 0 85 2 51 showed significant association ihbc alp significantly associated gbtc risk alp 1 59 95 ci 1 20 2 09 conclusion study shows positive associations circulating liver biomarkers sera collected prior cancer diagnoses risks developing hcc ihbc gbtc pubmed","probabilities":0.9799733,"Title":"Prospective association of liver function biomarkers with development of hepatobiliary cancers","Abstract":"INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers. METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI). RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09). CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.","Source":"PubMed","category":"HUMAN","training_data":"Prospective association of liver function biomarkers with development of hepatobiliary cancers INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers. METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI). RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09). CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder cancer afc gbc 2009 study group background incidental gallbladder cancer gbc frequently discovered specimen cholecystectomy benign disease performed objective present study assess management incidental gbc patients french registry methods data patients gbc treated 1998 2008 retrospectively collated french multicenter database results registry contained 218 patients incidental gbc 67 men 151 women median age 64 years age range 31 88 one hundred forty eight 68 patients underwent re resection median time interval 48 days range 2 245 common complete procedure 66 cases 4b 5 segmentectomy lymphadenectomy bile duct resection port site excision performed 54 patients mortality morbidity rates 3 37 respectively resection common bile duct 43 increased postoperative complications 60 vs 23 p 0 0001 local residual tumor found 83 56 patients significantly correlated stage influenced long term survival r0 obtained 143 97 patients port site invasion histologically confirmed one patient 1 8 median follow period 34 months 1 3 5 year survival rates 148 patients re resection 76 54 41 respectively re resection significantly increased survival patients t2 p 0 0001 t3 p 0 04 disease resection common bile duct increased neither r0 resection overall survival p 0 06 conclusion study validates concept re resection t2 t3 gbc bile duct resection increases postoperative morbidity improve survival currently modification surgical management incidental gbc minor liver resection common bile duct resection stn","probabilities":0.9799733,"Title":"Incidental Gallbladder Cancer By The Afc-Gbc-2009 Study Group","Abstract":"Background: Incidental gallbladder cancer (GBC) is frequently discovered on the specimen when cholecystectomy for a benign disease is performed. The objective of the present study was to assess the management of incidental GBC patients in a French registry. \r\n\r\n Methods: Data on patients with GBC treated between 1998 and 2008 were retrospectively collated in a French, multicenter database. \r\n\r\n Results: The registry contained 218 patients with incidental GBC (67 men and 151 women; median age = 64 years; age range = 31-88). One hundred forty-eight (68%) patients underwent re-resection after a median time interval of 48 days (range = 2-245). The most common complete procedure (66% of cases) was 4b + 5 segmentectomy with lymphadenectomy but not bile duct resection. Port-site excision was performed in 54 patients. The mortality and morbidity rates were 3 and 37%, respectively. Resection of the common bile duct (43%) increased postoperative complications (60 vs. 23%, p = 0.0001). Local residual tumor was found in 83 (56%) patients; it was significantly correlated with the T stage and influenced long-term survival. R0 was obtained in 143 (97%) patients and port-site invasion was histologically confirmed in one patient (1.8%). After a median follow-up period of 34 months, the 1-, 3-, and 5-year survival rates for the 148 patients with re-resection were 76, 54, and 41%, respectively. Re-resection significantly increased survival in patients with T2 (p = 0.0001) and T3 (p = 0.04) disease. Resection of the common bile duct increased neither R0 resection nor overall survival (p = 0.06). \r\n\r\n Conclusion: This study validates the concept of re-resection in T2 and T3 GBC. Bile duct resection increases postoperative morbidity but does not improve survival. There is currently a modification in the surgical management of incidental GBC, with minor liver resection and no common bile duct resection.","Source":"STN","category":"HUMAN","training_data":"Incidental Gallbladder Cancer By The Afc-Gbc-2009 Study Group Background: Incidental gallbladder cancer (GBC) is frequently discovered on the specimen when cholecystectomy for a benign disease is performed. The objective of the present study was to assess the management of incidental GBC patients in a French registry. \r\n\r\n Methods: Data on patients with GBC treated between 1998 and 2008 were retrospectively collated in a French, multicenter database. \r\n\r\n Results: The registry contained 218 patients with incidental GBC (67 men and 151 women; median age = 64 years; age range = 31-88). One hundred forty-eight (68%) patients underwent re-resection after a median time interval of 48 days (range = 2-245). The most common complete procedure (66% of cases) was 4b + 5 segmentectomy with lymphadenectomy but not bile duct resection. Port-site excision was performed in 54 patients. The mortality and morbidity rates were 3 and 37%, respectively. Resection of the common bile duct (43%) increased postoperative complications (60 vs. 23%, p = 0.0001). Local residual tumor was found in 83 (56%) patients; it was significantly correlated with the T stage and influenced long-term survival. R0 was obtained in 143 (97%) patients and port-site invasion was histologically confirmed in one patient (1.8%). After a median follow-up period of 34 months, the 1-, 3-, and 5-year survival rates for the 148 patients with re-resection were 76, 54, and 41%, respectively. Re-resection significantly increased survival in patients with T2 (p = 0.0001) and T3 (p = 0.04) disease. Resection of the common bile duct increased neither R0 resection nor overall survival (p = 0.06). \r\n\r\n Conclusion: This study validates the concept of re-resection in T2 and T3 GBC. Bile duct resection increases postoperative morbidity but does not improve survival. There is currently a modification in the surgical management of incidental GBC, with minor liver resection and no common bile duct resection. STN","prediction_labels":"HUMAN"},{"cleaned":"survival outcomes progonostic factors extrahepatic cholangiocarcinoma patients following surgical resection adjuvant therapy favorable prognostic factor study conducted investigate survival prognostic factors extrahepatic cholangiocarcinoma ecc following surgical resection evaluate effects postoperative adjuvant therapy overall survival os retrospectively collected clinical pathological data march 2008 december 2013 kaplan meier method cox regression model used evaluate os prognostic factors 105 postoperative ecc patients 32 received patients stratified seven risk subgroups survival rates compared within subgroup patients received results demonstrated median os 17 6 months 1 3 year survival rates 67 9 19 5 respectively entire cohort univariate analysis preoperative cholangitis non r0 surgical margins poor differentiation grade stage 3 4 lymphatic metastasis identified adverse prognostic factors significantly associated improved os however subgroup analysis revealed effect significant lymphatic metastasis group median os 21 6 vs 10 4 months 3 year os 16 6 vs 0 respectively p 0 02 survival curves non groups significantly different node positive patients cox regression model identified lymphatic metastasis surgical margins independent prognostic factors ecc negative resection margin may reduce mortality rate following surgery 47 contrast lymph node metastasis associated 2 18 fold higher mortality rate ecc patients postoperative contributed 0 45 fold mortality rate compared non ecc patients therefore concluded favorable prognostic factor ecc patients may prolong survival patients lymphatic metastasis data suggest postoperative recommended node positive ecc patients stn","probabilities":0.9799733,"Title":"Survival Outcomes And Progonostic Factors Of Extrahepatic Cholangiocarcinoma Patients Following Surgical Resection: Adjuvant Therapy Is A Favorable Prognostic Factor","Abstract":"This study was conducted to investigate survival and prognostic factors for extrahepatic cholangiocarcinoma (ECC) following surgical resection and evaluate the effects of postoperative adjuvant therapy (AT) on overall survival (OS). We retrospectively collected clinical and pathological data between March, 2008 and December, 2013. The Kaplan-Meier method and the COX regression model were used to evaluate the OS and prognostic factors of 105 postoperative ECC patients, of whom 32 had received AT. The patients were stratified into seven risk subgroups and the survival rates were compared within each subgroup between patients who received AT and those who did not. The results demonstrated a median OS of 17.6 months, with 1- and 3-year survival rates of 67.9 and 19.5%, respectively, for the entire cohort. On univariate analysis, preoperative cholangitis, non-R0 surgical margins, poor differentiation grade, stage 3/4 and lymphatic metastasis were identified as adverse prognostic factors. AT was not significantly associated with improved OS. However, the subgroup analysis revealed that the effect of AT was significant only in the lymphatic metastasis group (median OS, 21.6 vs. 10.4 months; and 3-year OS, 16.6 vs. 0%, respectively; P=0.02). The survival curves of the AT and non-AT groups were significantly different only for node-positive patients. The COX regression model identified lymphatic metastasis, surgical margins and AT as independent prognostic factors for ECC. A negative resection margin may reduce the mortality rate following surgery by 47%. By contrast, lymph node metastasis was associated with a 2.18-fold higher mortality rate for ECC patients. Postoperative AT contributed to a 0.45-fold mortality rate compared to non-AT ECC patients. Therefore, we concluded that AT is a favorable prognostic factor for ECC patients and it may prolong the survival of patients with lymphatic metastasis. Our data suggest that postoperative AT should be recommended for node-positive ECC patients.","Source":"STN","category":"HUMAN","training_data":"Survival Outcomes And Progonostic Factors Of Extrahepatic Cholangiocarcinoma Patients Following Surgical Resection: Adjuvant Therapy Is A Favorable Prognostic Factor This study was conducted to investigate survival and prognostic factors for extrahepatic cholangiocarcinoma (ECC) following surgical resection and evaluate the effects of postoperative adjuvant therapy (AT) on overall survival (OS). We retrospectively collected clinical and pathological data between March, 2008 and December, 2013. The Kaplan-Meier method and the COX regression model were used to evaluate the OS and prognostic factors of 105 postoperative ECC patients, of whom 32 had received AT. The patients were stratified into seven risk subgroups and the survival rates were compared within each subgroup between patients who received AT and those who did not. The results demonstrated a median OS of 17.6 months, with 1- and 3-year survival rates of 67.9 and 19.5%, respectively, for the entire cohort. On univariate analysis, preoperative cholangitis, non-R0 surgical margins, poor differentiation grade, stage 3/4 and lymphatic metastasis were identified as adverse prognostic factors. AT was not significantly associated with improved OS. However, the subgroup analysis revealed that the effect of AT was significant only in the lymphatic metastasis group (median OS, 21.6 vs. 10.4 months; and 3-year OS, 16.6 vs. 0%, respectively; P=0.02). The survival curves of the AT and non-AT groups were significantly different only for node-positive patients. The COX regression model identified lymphatic metastasis, surgical margins and AT as independent prognostic factors for ECC. A negative resection margin may reduce the mortality rate following surgery by 47%. By contrast, lymph node metastasis was associated with a 2.18-fold higher mortality rate for ECC patients. Postoperative AT contributed to a 0.45-fold mortality rate compared to non-AT ECC patients. Therefore, we concluded that AT is a favorable prognostic factor for ECC patients and it may prolong the survival of patients with lymphatic metastasis. Our data suggest that postoperative AT should be recommended for node-positive ECC patients. STN","prediction_labels":"HUMAN"},{"cleaned":"improved survival african american males intrahepatic cholangiocarcinoma largely due increased operative treatment introduction historically us racial inequality major determinant outcomes secondary resultant distrust healthcare system disparages medical care access specifically african americans aa intrahepatic cholangiocarcinoma icca reported worse survival racial groups evaluation impact race treatment survival icca us past 20 years undertaken methods mortality survival rates whites aa blacks hispanics histologically proven icca obtained surveillance epidemiology end results survey seer database comparative subgroup examination white vs black males also performed results 2297 patients white 2003 black 148 hispanic 146 histologically proven icca 1989 1998 1206 1999 2008 1091 black males icca remained stable time 3 2 vs 3 5 89 98 significant difference kaplan meier survival found white black males p 0 005 99 08 survival black males matched white males statistically significant differences survival race gender 99 208 found blacks undergoing surgery similar whites 18 4 vs 16 contrast first time period 5 vs 11 6 substantial decreases blacks seen recommending 72 41 contraindications 15 4 0 refusal surgery 1 4 1 conclusion survival black males histologically proven icca appears equivalent white males us due mainly increased operative treatment racial inequality seems moving toward extinction regard treatment disease google scholar","probabilities":0.9799733,"Title":"Improved Survival In African American Males With Intrahepatic Cholangiocarcinoma Largely Due To Increased Operative Treatment","Abstract":"Introduction: Historically, in the US racial inequality has been a major determinant in outcomes secondary to its resultant distrust of the healthcare system and disparages in medical care access. More specifically, African Americans (AA) with intrahepatic cholangiocarcinoma (ICCA) have been reported to have worse survival than other racial groups. Evaluation of the impact of race on treatment and survival in ICCA in the US over the past 20 years was undertaken. Methods: Mortality and survival rates for Whites, AA (Blacks), and Hispanics with histologically proven ICCA were obtained from the surveillance, epidemiology and end results survey (SEER) database. Comparative subgroup examination of White vs. Black males was also performed. Results: 2297 patients (White = 2003, Black = 148, Hispanic = 146) had histologically proven ICCA (1989–1998 = 1206, 1999–2008 = 1091). The % of Black males with ICCA remained stable over time (3.2% vs. 3.5%). From 89–98, the only significant difference in Kaplan-Meier survival was found between White and Black males (p < 0.005). From 99–08, survival of Black males matched that of White males. No statistically significant differences in survival for any other race or gender from 99–208 were found. In Blacks, the % undergoing surgery is now similar to Whites (18.4% vs. 16%) in contrast to the first time period (5% vs. 11.6%). Substantial decreases for Blacks were seen in: not recommending (72% to 41%), contraindications to (15.4% to 0%), and refusal of surgery (1.4% to 1%). Conclusion: The survival of Black males with histologically proven ICCA, appears to now be equivalent to White males in the US and due mainly to increased operative treatment. Further, racial inequality seems to be moving toward extinction in regard to the treatment of this disease.","Source":"Google Scholar","category":"HUMAN","training_data":"Improved Survival In African American Males With Intrahepatic Cholangiocarcinoma Largely Due To Increased Operative Treatment Introduction: Historically, in the US racial inequality has been a major determinant in outcomes secondary to its resultant distrust of the healthcare system and disparages in medical care access. More specifically, African Americans (AA) with intrahepatic cholangiocarcinoma (ICCA) have been reported to have worse survival than other racial groups. Evaluation of the impact of race on treatment and survival in ICCA in the US over the past 20 years was undertaken. Methods: Mortality and survival rates for Whites, AA (Blacks), and Hispanics with histologically proven ICCA were obtained from the surveillance, epidemiology and end results survey (SEER) database. Comparative subgroup examination of White vs. Black males was also performed. Results: 2297 patients (White = 2003, Black = 148, Hispanic = 146) had histologically proven ICCA (1989–1998 = 1206, 1999–2008 = 1091). The % of Black males with ICCA remained stable over time (3.2% vs. 3.5%). From 89–98, the only significant difference in Kaplan-Meier survival was found between White and Black males (p < 0.005). From 99–08, survival of Black males matched that of White males. No statistically significant differences in survival for any other race or gender from 99–208 were found. In Blacks, the % undergoing surgery is now similar to Whites (18.4% vs. 16%) in contrast to the first time period (5% vs. 11.6%). Substantial decreases for Blacks were seen in: not recommending (72% to 41%), contraindications to (15.4% to 0%), and refusal of surgery (1.4% to 1%). Conclusion: The survival of Black males with histologically proven ICCA, appears to now be equivalent to White males in the US and due mainly to increased operative treatment. Further, racial inequality seems to be moving toward extinction in regard to the treatment of this disease. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"dynamic change total bilirubin portal vein embolization predictive major complications posthepatectomy mortality patients hilar cholangiocarcinoma objectives study aims evaluate role dynamic change total bilirubin portal vein embolization pve predicting major complications 30 day mortality patients hilar cholangiocarcinoma hcca methods retrospective analysis prospectively maintained data 64 hcca patients underwent pve hepatectomy institution used total bilirubin parameters measured daily peri pve period difference baseline value days 0 5 day 1 d1 days 5 14 day 1 d2 calculated relationship d1 d2 total bilirubin major complications well 30 day mortality analyzed results 64 patients 10 developed major complications 15 6 6 patients 9 3 died within 30 days surgery d2 total bilirubin pve significantly associated major complications p 0 001 30 day mortality p 0 002 addition found independent predictor major complications pve odds ratio 1 050 95 ci 1 017 1 084 asa 3 12 048 95 ci 1 019 143 321 d2 total bilirubin 1 058 95 ci 1 007 1 112 d2 prealbumin 0 975 95 ci 0 952 0 999 associated higher risk 30 day mortality pve receiver operating characteristic curves showed d2 total bilirubin better predictors d1 major complications auc d2 0 817 p 0 002 vs auc d1 0 769 p 0 007 30 day mortality acu d2 0 868 p 0 003 vs auc d1 0 721 p 0 076 conclusion patients increased total bilirubin 5 14 days pve may indicate higher risk major complications 30 day mortality major hepatectomy performed pubmed","probabilities":0.9799733,"Title":"Dynamic Change of Total Bilirubin after Portal Vein Embolization is Predictive of Major Complications and Posthepatectomy Mortality in Patients with Hilar Cholangiocarcinoma","Abstract":"OBJECTIVES: This study aims to evaluate the role of dynamic change in total bilirubin after portal vein embolization (PVE) in predicting major complications and 30-day mortality in patients with hilar cholangiocarcinoma (HCCA). METHODS: Retrospective analysis of prospectively maintained data of 64 HCCA patients who underwent PVE before hepatectomy in our institution was used. Total bilirubin and other parameters were measured daily in peri-PVE period. The difference between them and the baseline value from days 0-5 to day -1 (∆D1) and days 5-14 to day -1 (∆D2) were calculated. The relationship between ∆D1 and ∆D2 of total bilirubin and major complications as well as 30-day mortality was analyzed. RESULTS: Out of 64 patients, 10 developed major complications (15.6 %) and 6 patients (9.3 %) had died within 30 days after surgery. The ∆D2 of total bilirubin after PVE was most significantly associated with major complications (P < 0.001) and 30-day mortality (P = 0.002). In addition, it was found to be an independent predictor of major complications after PVE (odds ratio (OR) = 1.050; 95 % CI 1.017-1.084). ASA >3 (OR = 12.048; 95 % CI 1.019-143.321), ∆D2 of total bilirubin (OR = 1.058; 95 % CI 1.007-1.112), and ∆D2 of prealbumin (OR = 0.975; 95 % CI 0.952-0.999) were associated with higher risk of 30-day mortality after PVE. Receiver operating characteristic curves showed that ∆D2 of total bilirubin were better predictors than ∆D1 for major complications (AUC (∆D2) 0.817; P = 0.002 vs. AUC (∆D1) 0.769; P = 0.007) and 30-day mortality (ACU(∆D2) 0.868; P = 0.003 vs. AUC(∆D1) 0.721;P = 0.076). CONCLUSION: Patients with increased total bilirubin in 5-14 days after PVE may indicate a higher risk of major complications and 30-day mortality if the major hepatectomy were performed.","Source":"PubMed","category":"HUMAN","training_data":"Dynamic Change of Total Bilirubin after Portal Vein Embolization is Predictive of Major Complications and Posthepatectomy Mortality in Patients with Hilar Cholangiocarcinoma OBJECTIVES: This study aims to evaluate the role of dynamic change in total bilirubin after portal vein embolization (PVE) in predicting major complications and 30-day mortality in patients with hilar cholangiocarcinoma (HCCA). METHODS: Retrospective analysis of prospectively maintained data of 64 HCCA patients who underwent PVE before hepatectomy in our institution was used. Total bilirubin and other parameters were measured daily in peri-PVE period. The difference between them and the baseline value from days 0-5 to day -1 (∆D1) and days 5-14 to day -1 (∆D2) were calculated. The relationship between ∆D1 and ∆D2 of total bilirubin and major complications as well as 30-day mortality was analyzed. RESULTS: Out of 64 patients, 10 developed major complications (15.6 %) and 6 patients (9.3 %) had died within 30 days after surgery. The ∆D2 of total bilirubin after PVE was most significantly associated with major complications (P < 0.001) and 30-day mortality (P = 0.002). In addition, it was found to be an independent predictor of major complications after PVE (odds ratio (OR) = 1.050; 95 % CI 1.017-1.084). ASA >3 (OR = 12.048; 95 % CI 1.019-143.321), ∆D2 of total bilirubin (OR = 1.058; 95 % CI 1.007-1.112), and ∆D2 of prealbumin (OR = 0.975; 95 % CI 0.952-0.999) were associated with higher risk of 30-day mortality after PVE. Receiver operating characteristic curves showed that ∆D2 of total bilirubin were better predictors than ∆D1 for major complications (AUC (∆D2) 0.817; P = 0.002 vs. AUC (∆D1) 0.769; P = 0.007) and 30-day mortality (ACU(∆D2) 0.868; P = 0.003 vs. AUC(∆D1) 0.721;P = 0.076). CONCLUSION: Patients with increased total bilirubin in 5-14 days after PVE may indicate a higher risk of major complications and 30-day mortality if the major hepatectomy were performed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"new insights molecular pathogenesis intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma aggressive malignancy one devastating cancers gastrointestinal tract molecular mechanisms contributing pathogenesis cancers well understood recognition distinction cancers tumors perihilar extrahepatic distal cholangiocarcinoma hepatocellular carcinoma important defining pathogenesis new insights molecular mechanisms contributing disease pathogenesis emerging recent epidemiological genome wide profiling laboratory based studies contributed improved understanding risk factors genetic mutations pathophysiological mechanisms associated tumors contribution well established risk factors biliary tract inflammation key signaling pathways involved intrahepatic cholangiocarcinoma defined new insights several important implications molecular diagnosis therapy cancers pubmed","probabilities":0.9799733,"Title":"New insights into the molecular pathogenesis of intrahepatic cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma is an aggressive malignancy and is one of the most devastating cancers of the gastrointestinal tract. The molecular mechanisms contributing to the pathogenesis of these cancers are not well understood. The recognition and distinction of these cancers from other tumors such as perihilar or extrahepatic distal cholangiocarcinoma and hepatocellular carcinoma are important in defining the pathogenesis. New insights into molecular mechanisms contributing to disease pathogenesis are emerging from recent epidemiological, genome-wide profiling and laboratory based studies. These have contributed to an improved understanding of risk factors, genetic mutations and pathophysiological mechanisms that are associated with these tumors. The contribution of well-established risk factors such as biliary tract inflammation and key signaling pathways involved in intrahepatic cholangiocarcinoma are being further defined. These new insights have several important implications for both molecular diagnosis and therapy of these cancers.","Source":"PubMed","category":"HUMAN","training_data":"New insights into the molecular pathogenesis of intrahepatic cholangiocarcinoma Intrahepatic cholangiocarcinoma is an aggressive malignancy and is one of the most devastating cancers of the gastrointestinal tract. The molecular mechanisms contributing to the pathogenesis of these cancers are not well understood. The recognition and distinction of these cancers from other tumors such as perihilar or extrahepatic distal cholangiocarcinoma and hepatocellular carcinoma are important in defining the pathogenesis. New insights into molecular mechanisms contributing to disease pathogenesis are emerging from recent epidemiological, genome-wide profiling and laboratory based studies. These have contributed to an improved understanding of risk factors, genetic mutations and pathophysiological mechanisms that are associated with these tumors. The contribution of well-established risk factors such as biliary tract inflammation and key signaling pathways involved in intrahepatic cholangiocarcinoma are being further defined. These new insights have several important implications for both molecular diagnosis and therapy of these cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"multicentre study impact morbidity long term survival following hepatectomy intrahepatic cholangiocarcinoma background impact morbidity long term outcomes following liver resection intrahepatic cholangiocarcinoma currently unclear methods retrospective analysis consecutive patients underwent liver resection intrahepatic cholangiocarcinoma curative intent 24 university hospitals 1989 2009 severe morbidity defined complication dindo clavien grade iii iv patients severe morbidity compared without terms demographics pathology management morbidity overall survival disease free survival time recurrence independent predictors severe morbidity identified multivariable analysis results total 522 patients enrolled severe morbidity occurred 113 patients 21 6 per cent independent predictor overall survival hazard ratio 1 64 95 per cent c 1 21 2 23 age resection multifocal disease positive lymph node status r0 resection margin severe morbidity emerge independent predictor disease free survival independent predictors time recurrence included severe morbidity tumour size multifocal disease vascular invasion r0 resection margin major hepatectomy intraoperative transfusion independent predictors severe morbidity conclusion severe morbidity adversely affects overall survival following liver resection intrahepatic cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Multicentre study of the impact of morbidity on long-term survival following hepatectomy for intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: The impact of morbidity on long-term outcomes following liver resection for intrahepatic cholangiocarcinoma is currently unclear. METHODS: This was a retrospective analysis of all consecutive patients who underwent liver resection for intrahepatic cholangiocarcinoma with curative intent in 24 university hospitals between 1989 and 2009. Severe morbidity was defined as any complication of Dindo-Clavien grade III or IV. Patients with severe morbidity were compared with those without in terms of demographics, pathology, management, morbidity, overall survival, disease-free survival and time to recurrence. Independent predictors of severe morbidity were identified by multivariable analysis. RESULTS: A total of 522 patients were enrolled. Severe morbidity occurred in 113 patients (21·6 per cent) and was an independent predictor of overall survival (hazard ratio 1·64, 95 per cent c.i. 1·21 to 2·23), as were age at resection, multifocal disease, positive lymph node status and R0 resection margin. Severe morbidity did not emerge as an independent predictor of disease-free survival. Independent predictors of time to recurrence included severe morbidity, tumour size, multifocal disease, vascular invasion and R0 resection margin. Major hepatectomy and intraoperative transfusion were independent predictors of severe morbidity. CONCLUSION: Severe morbidity adversely affects overall survival following liver resection for intrahepatic cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Multicentre study of the impact of morbidity on long-term survival following hepatectomy for intrahepatic cholangiocarcinoma BACKGROUND: The impact of morbidity on long-term outcomes following liver resection for intrahepatic cholangiocarcinoma is currently unclear. METHODS: This was a retrospective analysis of all consecutive patients who underwent liver resection for intrahepatic cholangiocarcinoma with curative intent in 24 university hospitals between 1989 and 2009. Severe morbidity was defined as any complication of Dindo-Clavien grade III or IV. Patients with severe morbidity were compared with those without in terms of demographics, pathology, management, morbidity, overall survival, disease-free survival and time to recurrence. Independent predictors of severe morbidity were identified by multivariable analysis. RESULTS: A total of 522 patients were enrolled. Severe morbidity occurred in 113 patients (21·6 per cent) and was an independent predictor of overall survival (hazard ratio 1·64, 95 per cent c.i. 1·21 to 2·23), as were age at resection, multifocal disease, positive lymph node status and R0 resection margin. Severe morbidity did not emerge as an independent predictor of disease-free survival. Independent predictors of time to recurrence included severe morbidity, tumour size, multifocal disease, vascular invasion and R0 resection margin. Major hepatectomy and intraoperative transfusion were independent predictors of severe morbidity. CONCLUSION: Severe morbidity adversely affects overall survival following liver resection for intrahepatic cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"bmi gallbladder cancer risk systematic review meta analysis prospective studies abstract available google scholar","probabilities":0.9799733,"Title":"Bmi And Gallbladder Cancer Risk: A Systematic Review And Meta-Analysis Of Prospective Studies","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Bmi And Gallbladder Cancer Risk: A Systematic Review And Meta-Analysis Of Prospective Studies Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"improved oncologic outcome chemoradiotherapy followed surgery unresectable intrahepatic cholangiocarcinoma purpose investigate ability chemoradiotherapy crt stage unresectable intrahepatic cholangiocarcinoma ihcc resectable lesions well factors associated achieving staging methods study cohort comprised 120 patients diagnosed stage iva ihcc 2001 2012 patients 56 underwent surgery 64 received crt initial treatment rate curative resections patients received crt assessed locoregional failure free survival lrffs overall survival os rates patients compared patients underwent crt alone results median follow 36 months partial response crt observed 25 patients whereas biologic response 70 decrease ca19 9 observed 35 eight patients 12 5 received curative resection crt showed significantly improved lrffs os compared treated crt alone 3 year lrffs 50 vs 15 7 respectively p 0 03 3 year os 50 vs 11 2 respectively p 0 012 rates comparable patients received initial surgery factors associated curative surgery crt gemcitabine administration higher radiotherapy dose biological effective dose 55 gy 10 70 reduction ca19 9 conclusion upfront crt produce favorable outcomes converting unresectable lesions resectable tumors selected patients higher radiotherapy doses gemcitabine based chemotherapy yielded significant reduction ca19 9 crt patients characteristics greater chance curative resection improved os pubmed","probabilities":0.9799733,"Title":"Improved oncologic outcome with chemoradiotherapy followed by surgery in unresectable intrahepatic cholangiocarcinoma","Abstract":"PURPOSE: To investigate the ability of chemoradiotherapy (CRT) to down-stage unresectable intrahepatic cholangiocarcinoma (IHCC) to resectable lesions, as well as the factors associated with achieving such down-staging. METHODS: The study cohort comprised 120 patients diagnosed with stage I-IVA IHCC between 2001 and 2012. Of these patients, 56 underwent surgery and 64 received CRT as their initial treatment. The rate of curative resections for patients who received CRT was assessed, and the locoregional failure-free survival (LRFFS) and overall survival (OS) rates of these patients were compared to those of patients who underwent CRT alone. RESULTS: Median follow-up was 36 months. A partial response after CRT was observed in 25% of patients, whereas a biologic response (a >70% decrease of CA19-9) was observed in 35%. Eight patients (12.5%) received curative resection after CRT and showed significantly improved LRFFS and OS compared to those treated with CRT alone (3-year LRFFS: 50 vs. 15.7%, respectively, p = 0.03; 3‑year OS: 50 vs. 11.2%, respectively, p = 0.012); these rates were comparable to those of patients who received initial surgery. Factors associated with curative surgery after CRT were gemcitabine administration, higher radiotherapy dose (biological effective dose ≥55 Gy with α/β = 10), and a >70% reduction of CA19-9. CONCLUSION: Upfront CRT could produce favorable outcomes by converting unresectable lesions to resectable tumors in selected patients. Higher radiotherapy doses and gemcitabine-based chemotherapy yielded a significant reduction of CA19-9 after CRT; patients with these characteristics had a greater chance of curative resection and improved OS.","Source":"PubMed","category":"HUMAN","training_data":"Improved oncologic outcome with chemoradiotherapy followed by surgery in unresectable intrahepatic cholangiocarcinoma PURPOSE: To investigate the ability of chemoradiotherapy (CRT) to down-stage unresectable intrahepatic cholangiocarcinoma (IHCC) to resectable lesions, as well as the factors associated with achieving such down-staging. METHODS: The study cohort comprised 120 patients diagnosed with stage I-IVA IHCC between 2001 and 2012. Of these patients, 56 underwent surgery and 64 received CRT as their initial treatment. The rate of curative resections for patients who received CRT was assessed, and the locoregional failure-free survival (LRFFS) and overall survival (OS) rates of these patients were compared to those of patients who underwent CRT alone. RESULTS: Median follow-up was 36 months. A partial response after CRT was observed in 25% of patients, whereas a biologic response (a >70% decrease of CA19-9) was observed in 35%. Eight patients (12.5%) received curative resection after CRT and showed significantly improved LRFFS and OS compared to those treated with CRT alone (3-year LRFFS: 50 vs. 15.7%, respectively, p = 0.03; 3‑year OS: 50 vs. 11.2%, respectively, p = 0.012); these rates were comparable to those of patients who received initial surgery. Factors associated with curative surgery after CRT were gemcitabine administration, higher radiotherapy dose (biological effective dose ≥55 Gy with α/β = 10), and a >70% reduction of CA19-9. CONCLUSION: Upfront CRT could produce favorable outcomes by converting unresectable lesions to resectable tumors in selected patients. Higher radiotherapy doses and gemcitabine-based chemotherapy yielded a significant reduction of CA19-9 after CRT; patients with these characteristics had a greater chance of curative resection and improved OS. PubMed","prediction_labels":"HUMAN"},{"cleaned":"histopathological findings cholecystectomies specimens single institution study 20 584 cases background histopathological examination cholecystectomy specimens standardized debate concerning routine selective approach aim study assess information obtained routine histopathological examination cholecystectomy specimens methods histopathological reports cholecystectomy specimens january 2003 december 2016 analyzed including clinical diagnosis benign gallstone disease cholecystitis results total 20 584 reports examined mean age patients 54 2 years patients aged 60 years represent 37 6 study population patients 15 973 77 6 females incidental gallbladder cancers gbc present 155 cholecystectomies specimens 0 8 67 1 gbc t2 t3 stage granulomatous cholecystitis diagnosed 19 cases 0 1 gbc prevalent older patients p 10 6 cholesterolosis prevalent young patients p 10 6 gender predilection gbc p 0 739 conclusions rate incidental gallbladder carcinoma study low yet found higher proportion t2 t3 carcinomas stage granulomatous cholecystitis may need investigations treatments selective approch histopathological examination cholecystectomy specimens used important take account clinical parameters significantly associated gallbladder cancer stn","probabilities":0.9799733,"Title":"Histopathological Findings In Cholecystectomies Specimens: A Single Institution Study Of 20 584 Cases","Abstract":"Background: The histopathological examination of cholecystectomy specimens has not been standardized with a debate concerning the routine and the selective approach. The aim of this study was to assess the information obtained from routine histopathological examination of cholecystectomy specimens. \r\n\r\n Methods: All histopathological reports of cholecystectomy specimens between January 2003 and December 2016 were analyzed, including a clinical diagnosis of benign gallstone disease or cholecystitis. \r\n\r\n Results: A total of 20,584 reports were examined. The mean age of patients was 54.2 years. Patients aged more than 60 years represent 37.6% of the study population. Of all patients, 15,973 (77.6%) were females. Incidental gallbladder cancers (GBC) were present in 155 cholecystectomies specimens (0.8%). 67.1% of GBC are at T2 and T3 stage. Granulomatous cholecystitis was diagnosed in only 19 cases (0.1%). GBC were more prevalent in older patients (P < 10-6) and cholesterolosis was more prevalent in young patients (P < 10-6). There was no gender predilection for GBC (P = 0.739). \r\n\r\n Conclusions: The rate of incidental gallbladder carcinoma in our study is low, yet, we found a higher proportion of T2 and T3 carcinomas stage. Granulomatous cholecystitis may need further investigations and treatments. When a selective approch of histopathological examination of cholecystectomy specimens is used, it is important to take into account that clinical parameters are significantly associated with gallbladder cancer.","Source":"STN","category":"ANIMAL","training_data":"Histopathological Findings In Cholecystectomies Specimens: A Single Institution Study Of 20 584 Cases Background: The histopathological examination of cholecystectomy specimens has not been standardized with a debate concerning the routine and the selective approach. The aim of this study was to assess the information obtained from routine histopathological examination of cholecystectomy specimens. \r\n\r\n Methods: All histopathological reports of cholecystectomy specimens between January 2003 and December 2016 were analyzed, including a clinical diagnosis of benign gallstone disease or cholecystitis. \r\n\r\n Results: A total of 20,584 reports were examined. The mean age of patients was 54.2 years. Patients aged more than 60 years represent 37.6% of the study population. Of all patients, 15,973 (77.6%) were females. Incidental gallbladder cancers (GBC) were present in 155 cholecystectomies specimens (0.8%). 67.1% of GBC are at T2 and T3 stage. Granulomatous cholecystitis was diagnosed in only 19 cases (0.1%). GBC were more prevalent in older patients (P < 10-6) and cholesterolosis was more prevalent in young patients (P < 10-6). There was no gender predilection for GBC (P = 0.739). \r\n\r\n Conclusions: The rate of incidental gallbladder carcinoma in our study is low, yet, we found a higher proportion of T2 and T3 carcinomas stage. Granulomatous cholecystitis may need further investigations and treatments. When a selective approch of histopathological examination of cholecystectomy specimens is used, it is important to take into account that clinical parameters are significantly associated with gallbladder cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"diagnosis management intrahepatic extrahepatic cholangiocarcinoma cholangiocarcinomas cc rare tumors usually present late often difficult diagnose treat ccs categorized intrahepatic hilar extrahepatic epidemiologic studies suggest incidence intrahepatic ccs may increasing worldwide chapter review risk factors clinical presentation management cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Diagnosis and Management of Intrahepatic and Extrahepatic Cholangiocarcinoma","Abstract":"Cholangiocarcinomas (CC) are rare tumors which usually present late and are often difficult to diagnose and treat. CCs are categorized as intrahepatic, hilar, or extrahepatic. Epidemiologic studies suggest that the incidence of intrahepatic CCs may be increasing worldwide. In this chapter, we review the risk factors, clinical presentation, and management of cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Diagnosis and Management of Intrahepatic and Extrahepatic Cholangiocarcinoma Cholangiocarcinomas (CC) are rare tumors which usually present late and are often difficult to diagnose and treat. CCs are categorized as intrahepatic, hilar, or extrahepatic. Epidemiologic studies suggest that the incidence of intrahepatic CCs may be increasing worldwide. In this chapter, we review the risk factors, clinical presentation, and management of cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcome neoadjuvant chemotherapy locally advanced borderline resectable gallbladder cancer need define indications background studies evaluating neo adjuvant chemotherapy nact exclusively gallbladder cancer gbc randomized trials subject locally advanced gbc indications nact gbc yet clearly defined methods analysed 160 consecutive gbc patients received nact based clinico radiologic criteria suggesting high risk disease tmh criteria january 2010 february 2016 results initial assessment 140 87 5 patients t3 t4 disease 105 65 patients node positive response rate clinical benefit rate 52 5 70 respectively sixty six 41 2 patients undergo curative intent resection median follow 33 months median os efs entire cohort 13 8 months respectively patient undergoing curative surgery statistically superior os 49 vs 7 months p 0 0001 efs 25 months vs 5 months p 0 0001 compared conclusion locally advanced gbc remains disease poor prognosis chemotherapy neoadjuvant intent locally advanced borderline resectable gbc showed good response rates resulted curative surgical resection disease stabilisation significant proportion patients patients undergo definitive surgery favourable response nact experience good survival pubmed","probabilities":0.9799733,"Title":"Outcome of neoadjuvant chemotherapy in locally advanced/borderline resectable gallbladder cancer: the need to define indications","Abstract":"BACKGROUND: Studies evaluating neo-adjuvant chemotherapy (NACT) exclusively in gallbladder cancer (GBC) are few and there are no randomized trials on the subject. Locally advanced GBC and indications for NACT in GBC are not yet clearly defined. METHODS: We analysed 160 consecutive GBC patients who received NACT based on clinico-radiologic criteria suggesting high-risk disease (TMH Criteria) from January 2010 to February 2016. RESULTS: On initial assessment, 140 (87.5%) patients had T3/T4 disease and 105 (65%) patients were node positive. Response rate and clinical benefit rate was 52.5% and 70% respectively. Sixty six (41.2%) patients could undergo curative intent resection. With a median follow-up of 33 months, the median OS and EFS of the entire cohort were 13 and 8 months respectively. Patient undergoing curative surgery had a statistically superior OS (49 vs. 7 months; p = 0.0001) and EFS (25 months vs. 5 months; p = 0.0001) compared to those who did not. CONCLUSION: Locally advanced GBC remains a disease with poor prognosis. Chemotherapy with neoadjuvant intent in locally advanced/borderline resectable GBC showed good response rates. This resulted in curative surgical resection or disease stabilisation in significant proportion of patients. Patients who undergo definitive surgery after favourable response to NACT experience good survival.","Source":"PubMed","category":"HUMAN","training_data":"Outcome of neoadjuvant chemotherapy in locally advanced/borderline resectable gallbladder cancer: the need to define indications BACKGROUND: Studies evaluating neo-adjuvant chemotherapy (NACT) exclusively in gallbladder cancer (GBC) are few and there are no randomized trials on the subject. Locally advanced GBC and indications for NACT in GBC are not yet clearly defined. METHODS: We analysed 160 consecutive GBC patients who received NACT based on clinico-radiologic criteria suggesting high-risk disease (TMH Criteria) from January 2010 to February 2016. RESULTS: On initial assessment, 140 (87.5%) patients had T3/T4 disease and 105 (65%) patients were node positive. Response rate and clinical benefit rate was 52.5% and 70% respectively. Sixty six (41.2%) patients could undergo curative intent resection. With a median follow-up of 33 months, the median OS and EFS of the entire cohort were 13 and 8 months respectively. Patient undergoing curative surgery had a statistically superior OS (49 vs. 7 months; p = 0.0001) and EFS (25 months vs. 5 months; p = 0.0001) compared to those who did not. CONCLUSION: Locally advanced GBC remains a disease with poor prognosis. Chemotherapy with neoadjuvant intent in locally advanced/borderline resectable GBC showed good response rates. This resulted in curative surgical resection or disease stabilisation in significant proportion of patients. Patients who undergo definitive surgery after favourable response to NACT experience good survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"microrna aberrations emerging field gallbladder cancer management gallbladder cancer gbc infrequent lethal biliary tract malignancy characterized advanced stage diagnosis poor survival rates attributed absence specific symptoms effective treatment options necessitate development early prognostic predictive markers novel therapeutic interventions micrornas mirnas small non coding rna molecules play key role tumor biology functioning like tumor suppressor onco genes aberrant expression associated pathogenesis several neoplasms overwhelming clinical implications since mirna signature tissue specific focused current data concerning mirnas aberrations gbc pathogenesis gbc mirnas tumor suppressor activity mir 135 5p mir 335 mir 34a mir 26a mir 146b 5p mir 218 5p mir 1 mir 145 mir 130a found downregulated oncogenic property mir 20a mir 182 mir 155 upregulated expression profile mirnas significantly associated gbc prognosis prediction forced expression inhibition mirnas shown affect tumor growth development differential expression mirnas blood samples gbc patients suggest mirnas promising noninvasive biomarker thus mirnas represent potential candidate gbc management though many hurdles need overcome mirnas therapy clinically applied gbc prevention treatment pubmed","probabilities":0.7966102,"Title":"MicroRNA aberrations: An emerging field for gallbladder cancer management","Abstract":"Gallbladder cancer (GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or onco- genes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since miRNA signature is tissue specific, here, we focused on current data concerning the miRNAs aberrations in GBC pathogenesis. In GBC, miRNAs with tumor suppressor activity (miR-135-5p, miR-335, miR-34a, miR-26a, miR-146b-5p, Mir-218-5p, miR-1, miR-145, mir-130a) were found downregulated, while those with oncogenic property (miR-20a, miR-182, mir-155) were upregulated. The expression profile of miRNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these miRNAs was shown to affect tumor growth and development. Further, differential expression of miRNAs in the blood samples of GBC patients suggest miRNAs as promising noninvasive biomarker. Thus, miRNAs represent potential candidate for GBC management, though many hurdles need to be overcome before miRNAs therapy can be clinically applied to GBC prevention and treatment.","Source":"PubMed","category":"HUMAN","training_data":"MicroRNA aberrations: An emerging field for gallbladder cancer management Gallbladder cancer (GBC) is infrequent but most lethal biliary tract malignancy characterized by an advanced stage diagnosis and poor survival rates attributed to absence of specific symptoms and effective treatment options. These necessitate development of early prognostic/predictive markers and novel therapeutic interventions. MicroRNAs (miRNAs) are small, non-coding RNA molecules that play a key role in tumor biology by functioning like tumor suppressor- or onco- genes and their aberrant expression are associated with the pathogenesis of several neoplasms with overwhelming clinical implications. Since miRNA signature is tissue specific, here, we focused on current data concerning the miRNAs aberrations in GBC pathogenesis. In GBC, miRNAs with tumor suppressor activity (miR-135-5p, miR-335, miR-34a, miR-26a, miR-146b-5p, Mir-218-5p, miR-1, miR-145, mir-130a) were found downregulated, while those with oncogenic property (miR-20a, miR-182, mir-155) were upregulated. The expression profile of miRNAs was significantly associated with GBC prognosis and prediction, and forced over-expression/ inhibition of these miRNAs was shown to affect tumor growth and development. Further, differential expression of miRNAs in the blood samples of GBC patients suggest miRNAs as promising noninvasive biomarker. Thus, miRNAs represent potential candidate for GBC management, though many hurdles need to be overcome before miRNAs therapy can be clinically applied to GBC prevention and treatment. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gemcitabine plus platinum based chemotherapy first line treatment hepatocholangiocarcinoma ageo french multicentre retrospective study background hepatocholangiocarcinoma chcc icc rare liver tumour data chemosensitivity exist aims multicentre study evaluate overall survival os progression free survival pfs prognostic factors chcc icc treated gemcitabine plus platinum first line methods unresectable chcc icc treated gemcitabine plus platinum based chemotherapy 2008 2017 retrospectively analysed diagnosis based histology case icc hcc histology discordant computerised tomography scan enhancement patterns associated discordant serum tumour marker elevation suggesting alternative tumour os pfs evaluated kaplan meier method prognostic factors log rank test cox model results among 30 patients included chcc icc histologically proven 22 73 3 18 60 received gemcitabine plus oxaliplatin gemox 9 30 gemox plus bevacizumab 3 10 gemcitabine plus cisplatin recist criteria reported 28 patients 8 28 6 showed partial response 14 50 stable disease 6 21 4 tumour progression first evaluation median pfs os 9 0 16 2 months respectively serum bilirubin 30 mol l 1 p 0 001 positive serology hbv hcv p 0 014 independent poor prognostic factors os conclusions gemcitabine plus platinum based chemotherapy effective first line advanced chcc icc pubmed","probabilities":0.9799733,"Title":"Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study","Abstract":"BACKGROUND: Hepatocholangiocarcinoma (cHCC-ICC) is a rare liver tumour for which no data on chemosensitivity exist. The aims of this multicentre study were to evaluate overall survival (OS), progression-free survival (PFS), and prognostic factors in cHCC-ICC treated by gemcitabine plus platinum as first-line. METHODS: Unresectable cHCC-ICC treated by gemcitabine plus platinum-based chemotherapy between 2008 and 2017 were retrospectively analysed. Diagnosis was based on histology or, in case of ICC or HCC histology, on discordant computerised tomography scan enhancement patterns associated with discordant serum tumour marker elevation suggesting the alternative tumour. OS and PFS were evaluated by Kaplan-Meier method and prognostic factors by Log-rank test and Cox model. RESULTS: Among 30 patients included, cHCC-ICC was histologically proven in 22 (73.3%). 18 (60%) received gemcitabine plus oxaliplatin (GEMOX), 9 (30%) GEMOX plus bevacizumab, and 3 (10%) gemcitabine plus cisplatin. RECIST criteria were reported in 28 patients: 8 (28.6%) showed partial response, 14 (50%) stable disease, and 6 (21.4%) tumour progression at first evaluation. Median PFS and OS were 9.0 and 16.2 months, respectively. Serum bilirubin ⩾30 μmol l(-1) (P=0.001) and positive serology for HBV and/or HCV (P=0.014) were independent poor prognostic factors for OS. CONCLUSIONS: Gemcitabine plus platinum-based chemotherapy is effective as first-line for advanced cHCC-ICC.","Source":"PubMed","category":"HUMAN","training_data":"Gemcitabine plus platinum-based chemotherapy for first-line treatment of hepatocholangiocarcinoma: an AGEO French multicentre retrospective study BACKGROUND: Hepatocholangiocarcinoma (cHCC-ICC) is a rare liver tumour for which no data on chemosensitivity exist. The aims of this multicentre study were to evaluate overall survival (OS), progression-free survival (PFS), and prognostic factors in cHCC-ICC treated by gemcitabine plus platinum as first-line. METHODS: Unresectable cHCC-ICC treated by gemcitabine plus platinum-based chemotherapy between 2008 and 2017 were retrospectively analysed. Diagnosis was based on histology or, in case of ICC or HCC histology, on discordant computerised tomography scan enhancement patterns associated with discordant serum tumour marker elevation suggesting the alternative tumour. OS and PFS were evaluated by Kaplan-Meier method and prognostic factors by Log-rank test and Cox model. RESULTS: Among 30 patients included, cHCC-ICC was histologically proven in 22 (73.3%). 18 (60%) received gemcitabine plus oxaliplatin (GEMOX), 9 (30%) GEMOX plus bevacizumab, and 3 (10%) gemcitabine plus cisplatin. RECIST criteria were reported in 28 patients: 8 (28.6%) showed partial response, 14 (50%) stable disease, and 6 (21.4%) tumour progression at first evaluation. Median PFS and OS were 9.0 and 16.2 months, respectively. Serum bilirubin ⩾30 μmol l(-1) (P=0.001) and positive serology for HBV and/or HCV (P=0.014) were independent poor prognostic factors for OS. CONCLUSIONS: Gemcitabine plus platinum-based chemotherapy is effective as first-line for advanced cHCC-ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"overall survival clinical characteristics brca associated cholangiocarcinoma multicenter retrospective study background biliary tract malignancies particular cholangiocarcinomas cca rare tumors carry poor prognosis brca2 mutation carriers increased risk developing cca reported relative risk 5 according breast cancer linkage consortium addition risk potential therapeutic implications harboring somatic germline gl brca mutations therefore important define clinical characteristics gl somatic brca1 2 variants cca patients materials methods performed multicenter retrospective analysis cca patients diagnosed january 2000 december 2013 gl somatic variants brca1 2 genes detected gl mutations testing tumor next generation sequencing cases identified clinical databases participating institutions data including demographics clinical history surgical procedures systemic chemotherapy radiation extracted patients records results overall 18 cases identified 5 carriers gl brca1 2 mutations 4 brca2 1 brca1 13 harboring somatic variations 7 brca1 6 brca2 mean age diagnosis 60 sd 10 years range 36 75 years male female prevalence rates 61 2 38 8 respectively stage diagnosis n 4 ii n 3 iii n 3 iv n 8 six patients extrahepatic cca rest intrahepatic cca thirteen patients received platinum based therapy four treated poly adp ribose polymerase inhibitors one experienced sustained disease response progression free survival 42 6 months median overall survival diagnosis patients stage ii study 40 3 months 95 confidence interval ci 6 73 108 15 stages iii iv 25 months 95 ci 15 23 40 57 conclusion brca associated cca uncommon multicenter retrospective study provides thorough clinical analysis brca associated cca cohort serve benchmark future development design expanded analyses clinical trials implications practice brca associated cca uncommon important subtype hepatic malignancies due rising prevalence better clinical characterization subtype might allow application targeted therapy cca patients germline somatic mutations brca1 2 genes especially due previously reported success therapies brca associated malignancies thus study first kind provides basis future multi centered analyses larger cohorts well clinical trials additionally study emphasizes importance germline somatic genotyping cca patients pubmed","probabilities":0.9799733,"Title":"Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma: A Multicenter Retrospective Study","Abstract":"BACKGROUND: Biliary tract malignancies, in particular cholangiocarcinomas (CCA), are rare tumors that carry a poor prognosis. BRCA2 mutation carriers have an increased risk of developing CCA with a reported relative risk of ∼5 according to the Breast Cancer Linkage Consortium. In addition to this risk, there are potential therapeutic implications in those harboring somatic and/or germline (GL) BRCA mutations. Therefore, it is important to define the clinical characteristics of GL/somatic BRCA1/2 variants in CCA patients. MATERIALS AND METHODS: We performed a multicenter retrospective analysis of CCA patients diagnosed between January 2000 and December 2013 with GL or somatic variants in BRCA1/2 genes detected by GL mutations testing and/or by tumor next generation sequencing. Cases were identified from clinical databases at participating institutions. Data including demographics, clinical history, surgical procedures, and systemic chemotherapy or radiation were extracted from patients' records. RESULTS: Overall, 18 cases were identified: 5 carriers of GL BRCA1/2 mutations (4 BRCA2; 1 BRCA1) and 13 harboring somatic variations (7 BRCA1; 6 BRCA2). Mean age at diagnosis was 60, SD ± 10 years (range 36-75 years), with male and female prevalence rates of 61.2% and 38.8%, respectively. Stage at diagnosis was I (n = 4), II (n = 3), III (n = 3), and IV (n = 8). Six patients had extrahepatic CCA and the rest intrahepatic CCA. Thirteen patients received platinum-based therapy and four were treated with poly ADP ribose polymerase inhibitors, of whom one experienced sustained disease response with a progression-free survival of 42.6 months. Median overall survival from diagnosis for patients with stage I/II in this study was 40.3 months (95% confidence interval [CI], 6.73-108.15) and with stages III/IV was 25 months (95% CI, 15.23-40.57). CONCLUSION: BRCA-associated CCA is uncommon. This multicenter retrospective study provides a thorough clinical analysis of a BRCA-associated CCA cohort, which can serve as a benchmark for future development and design of expanded analyses and clinical trials. IMPLICATIONS FOR PRACTICE: BRCA-associated CCA is uncommon but a very important subtype of hepatic malignancies, due to its rising prevalence. Better clinical characterization of this subtype might allow application of targeted therapy for CCA patients with germline or somatic mutations in BRCA1/2 genes, especially due to previously reported success of such therapies in other BRCA-associated malignancies. Thus this study, first of its kind, provides a basis for future multi-centered analyses in larger cohorts, as well as clinical trials. Additionally, this study emphasizes the importance of both germline and somatic genotyping for all CCA patients.","Source":"PubMed","category":"HUMAN","training_data":"Overall Survival and Clinical Characteristics of BRCA-Associated Cholangiocarcinoma: A Multicenter Retrospective Study BACKGROUND: Biliary tract malignancies, in particular cholangiocarcinomas (CCA), are rare tumors that carry a poor prognosis. BRCA2 mutation carriers have an increased risk of developing CCA with a reported relative risk of ∼5 according to the Breast Cancer Linkage Consortium. In addition to this risk, there are potential therapeutic implications in those harboring somatic and/or germline (GL) BRCA mutations. Therefore, it is important to define the clinical characteristics of GL/somatic BRCA1/2 variants in CCA patients. MATERIALS AND METHODS: We performed a multicenter retrospective analysis of CCA patients diagnosed between January 2000 and December 2013 with GL or somatic variants in BRCA1/2 genes detected by GL mutations testing and/or by tumor next generation sequencing. Cases were identified from clinical databases at participating institutions. Data including demographics, clinical history, surgical procedures, and systemic chemotherapy or radiation were extracted from patients' records. RESULTS: Overall, 18 cases were identified: 5 carriers of GL BRCA1/2 mutations (4 BRCA2; 1 BRCA1) and 13 harboring somatic variations (7 BRCA1; 6 BRCA2). Mean age at diagnosis was 60, SD ± 10 years (range 36-75 years), with male and female prevalence rates of 61.2% and 38.8%, respectively. Stage at diagnosis was I (n = 4), II (n = 3), III (n = 3), and IV (n = 8). Six patients had extrahepatic CCA and the rest intrahepatic CCA. Thirteen patients received platinum-based therapy and four were treated with poly ADP ribose polymerase inhibitors, of whom one experienced sustained disease response with a progression-free survival of 42.6 months. Median overall survival from diagnosis for patients with stage I/II in this study was 40.3 months (95% confidence interval [CI], 6.73-108.15) and with stages III/IV was 25 months (95% CI, 15.23-40.57). CONCLUSION: BRCA-associated CCA is uncommon. This multicenter retrospective study provides a thorough clinical analysis of a BRCA-associated CCA cohort, which can serve as a benchmark for future development and design of expanded analyses and clinical trials. IMPLICATIONS FOR PRACTICE: BRCA-associated CCA is uncommon but a very important subtype of hepatic malignancies, due to its rising prevalence. Better clinical characterization of this subtype might allow application of targeted therapy for CCA patients with germline or somatic mutations in BRCA1/2 genes, especially due to previously reported success of such therapies in other BRCA-associated malignancies. Thus this study, first of its kind, provides a basis for future multi-centered analyses in larger cohorts, as well as clinical trials. Additionally, this study emphasizes the importance of both germline and somatic genotyping for all CCA patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatitis b virus associated intrahepatic cholangiocarcinoma malignancy distinctive characteristics hepatocellular carcinoma intrahepatic cholangiocarcinoma decade since hepatitis b virus infection identified etiological factor development intrahepatic cholangiocarcinoma icc recent years several studies elucidated critical impact hepatitis b virus icc significantly influenced clinicopathological characteristics icc patients intrahepatic cholangiocarcinoma distinctive features patients hepatitis b virus associated icc included younger age preponderance male patients frequent elevation alpha fetoprotein infrequent lymph node metastasis furthermore several studies indicated presence hepatitis b virus favorable prognostic factor terms overall survival relapse free survival however also studies demonstrating hepatitis b virus negatively influenced showed significant association survival outcomes patients icc present consensus diagnostic procedures treatments population therefore elucidated current knowledge recent identifications hbv associated icc clarify impact chronic hbv infection patients icc precisely conduct diagnostic procedures curative treatments hbv associated icc pubmed","probabilities":0.9799733,"Title":"Hepatitis B virus-associated intrahepatic cholangiocarcinoma: a malignancy of distinctive characteristics between hepatocellular carcinoma and intrahepatic cholangiocarcinoma","Abstract":"It has been a decade since hepatitis B virus infection was identified as an etiological factor for the development of intrahepatic cholangiocarcinoma (ICC). In recent years, several studies have elucidated the critical impact of hepatitis B virus in ICC that significantly influenced the clinicopathological characteristics of ICC patients with intrahepatic cholangiocarcinoma. Distinctive features of patients with hepatitis B virus-associated ICC included younger age, preponderance of male patients, frequent elevation of alpha-fetoprotein, and infrequent lymph node metastasis. Furthermore, several studies indicated that the presence of hepatitis B virus is a favorable prognostic factor in terms of overall survival and relapse-free survival. However, there are also a few studies demonstrating that hepatitis B virus negatively influenced or showed no significant association with survival outcomes of patients with ICC. At present, there are no consensus on diagnostic procedures and treatments for such population. Therefore, we elucidated current knowledge and recent identifications of HBV-associated ICC to clarify the impact of chronic HBV infection on patients with ICC and to precisely conduct diagnostic procedures and curative treatments for HBV-associated ICC.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis B virus-associated intrahepatic cholangiocarcinoma: a malignancy of distinctive characteristics between hepatocellular carcinoma and intrahepatic cholangiocarcinoma It has been a decade since hepatitis B virus infection was identified as an etiological factor for the development of intrahepatic cholangiocarcinoma (ICC). In recent years, several studies have elucidated the critical impact of hepatitis B virus in ICC that significantly influenced the clinicopathological characteristics of ICC patients with intrahepatic cholangiocarcinoma. Distinctive features of patients with hepatitis B virus-associated ICC included younger age, preponderance of male patients, frequent elevation of alpha-fetoprotein, and infrequent lymph node metastasis. Furthermore, several studies indicated that the presence of hepatitis B virus is a favorable prognostic factor in terms of overall survival and relapse-free survival. However, there are also a few studies demonstrating that hepatitis B virus negatively influenced or showed no significant association with survival outcomes of patients with ICC. At present, there are no consensus on diagnostic procedures and treatments for such population. Therefore, we elucidated current knowledge and recent identifications of HBV-associated ICC to clarify the impact of chronic HBV infection on patients with ICC and to precisely conduct diagnostic procedures and curative treatments for HBV-associated ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"staging prognostic factors adjuvant therapy intrahepatic cholangiocarcinoma curative resection background aims prognostic factors adjuvant therapy intrahepatic cholangiocarcinoma icc curative resection clear aim analyse prognostic factors curative resection evaluate adjuvant therapy survival based new staging system methods retrospective analysis 283 patients underwent surgical exploration icc performed staging performed according 7th edition ajcc staging manual univariate multivariate analyses used evaluate independent prognostic factors results difference os different tnm stages r0 resection significant p 0 001 despite regional lymph node metastasis tumour number vascular invasion serum ggt level also independent prognostic factor os patients r0 resection incidence biliary vascular invasion significantly higher high ggt group normal ggt group factors predictive recurrence multiple tumours regional lymph node metastasis r0 resection adjuvant tace improve os patients tnm stage p 0 508 significantly promoted recurrence patients p 0 006 patients tnm stage ii iii iv benefited adjuvant tace longer survival recurrence rates affected conclusions new staging system predict survival icc patients r0 resection high ggt level may suggestive biliary vascular invasion independent risk factor os r0 resection adjuvant tace may indicated patients advanced stages better survival pubmed","probabilities":0.9799733,"Title":"Staging, prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma after curative resection","Abstract":"BACKGROUND & AIMS: Prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma (ICC) after curative resection were not clear. We aim to analyse prognostic factors after curative resection and evaluate adjuvant therapy and survival based on the new staging system. METHODS: A retrospective analysis of 283 patients who underwent surgical exploration for ICC was performed. Staging was performed according to the 7th edition AJCC staging manual. Univariate and multivariate analyses were used to evaluate independent prognostic factors. RESULTS: The difference for OS at different TNM stages after R0 resection was significant (P < 0.001). Despite regional lymph node metastasis, tumour number and vascular invasion, serum GGT level was also an independent prognostic factor for OS of patients after R0 resection. The incidence of biliary and vascular invasion was significantly higher in high GGT group than in normal GGT group. Factors predictive of recurrence were multiple tumours and regional lymph node metastasis. After R0 resection, adjuvant TACE not only did not improve the OS of patients at TNM stage I (P = 0.508), but significantly promoted recurrence of these patients (P = 0.006). Only patients at TNM stage II, III and IV benefited from adjuvant TACE for longer survival, while the recurrence rates were not affected. CONCLUSIONS: The new staging system can predict the survival of ICC patients after R0 resection. High GGT level may be suggestive of biliary and vascular invasion and was an independent risk factor for OS after R0 resection. Adjuvant TACE may be indicated only for patients at advanced stages for better survival.","Source":"PubMed","category":"HUMAN","training_data":"Staging, prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma after curative resection BACKGROUND & AIMS: Prognostic factors and adjuvant therapy of intrahepatic cholangiocarcinoma (ICC) after curative resection were not clear. We aim to analyse prognostic factors after curative resection and evaluate adjuvant therapy and survival based on the new staging system. METHODS: A retrospective analysis of 283 patients who underwent surgical exploration for ICC was performed. Staging was performed according to the 7th edition AJCC staging manual. Univariate and multivariate analyses were used to evaluate independent prognostic factors. RESULTS: The difference for OS at different TNM stages after R0 resection was significant (P < 0.001). Despite regional lymph node metastasis, tumour number and vascular invasion, serum GGT level was also an independent prognostic factor for OS of patients after R0 resection. The incidence of biliary and vascular invasion was significantly higher in high GGT group than in normal GGT group. Factors predictive of recurrence were multiple tumours and regional lymph node metastasis. After R0 resection, adjuvant TACE not only did not improve the OS of patients at TNM stage I (P = 0.508), but significantly promoted recurrence of these patients (P = 0.006). Only patients at TNM stage II, III and IV benefited from adjuvant TACE for longer survival, while the recurrence rates were not affected. CONCLUSIONS: The new staging system can predict the survival of ICC patients after R0 resection. High GGT level may be suggestive of biliary and vascular invasion and was an independent risk factor for OS after R0 resection. Adjuvant TACE may be indicated only for patients at advanced stages for better survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"emerging molecular therapeutic targets cholangiocarcinoma cholangiocarcinomas ccas diverse epithelial tumors arising liver large bile ducts features cholangiocyte differentiation ccas classified anatomically intrahepatic icca perihilar pcca distal cca dcca subtype distinct risk factors molecular pathogenesis therapeutic options prognosis cca aggressive malignancy poor overall prognosis median survival less 2years patients advanced disease potentially curative surgical treatment options limited subset patients early stage disease presently available systemic medical therapies advanced metastatic cca limited therapeutic efficacy molecular alterations define differences biological behavior cca subtype recent comprehensive genetic analysis better characterized genomic transcriptomic landscape cca subtype promising candidates targeted personalized therapy emerged including potential driver fibroblast growth factor receptor fgfr gene fusions somatic mutations isocitrate dehydrogenase idh 1 2 icca protein kinase camp activated catalytic subunit alpha prkaca beta prkacb gene fusions pcca elf3 mutations dcca ampullary carcinoma precision genomic medicine approach dependent enhanced understanding driver mutations subtype stratification patients according genetic drivers review current genomic landscape cca potentially actionable molecular aberrations cca subtype role immunotherapy cca pubmed","probabilities":0.9799733,"Title":"Emerging molecular therapeutic targets for cholangiocarcinoma","Abstract":"Cholangiocarcinomas (CCAs) are diverse epithelial tumors arising from the liver or large bile ducts with features of cholangiocyte differentiation. CCAs are classified anatomically into intrahepatic (iCCA), perihilar (pCCA), and distal CCA (dCCA). Each subtype has distinct risk factors, molecular pathogenesis, therapeutic options, and prognosis. CCA is an aggressive malignancy with a poor overall prognosis and median survival of less than 2years in patients with advanced disease. Potentially curative surgical treatment options are limited to the subset of patients with early-stage disease. Presently, the available systemic medical therapies for advanced or metastatic CCA have limited therapeutic efficacy. Molecular alterations define the differences in biological behavior of each CCA subtype. Recent comprehensive genetic analysis has better characterized the genomic and transcriptomic landscape of each CCA subtype. Promising candidates for targeted, personalized therapy have emerged, including potential driver fibroblast growth factor receptor (FGFR) gene fusions and somatic mutations in isocitrate dehydrogenase (IDH)1/2 in iCCA, protein kinase cAMP-activated catalytic subunit alpha (PRKACA) or beta (PRKACB) gene fusions in pCCA, and ELF3 mutations in dCCA/ampullary carcinoma. A precision genomic medicine approach is dependent on an enhanced understanding of driver mutations in each subtype and stratification of patients according to their genetic drivers. We review the current genomic landscape of CCA, the potentially actionable molecular aberrations in each CCA subtype, and the role of immunotherapy in CCA.","Source":"PubMed","category":"HUMAN","training_data":"Emerging molecular therapeutic targets for cholangiocarcinoma Cholangiocarcinomas (CCAs) are diverse epithelial tumors arising from the liver or large bile ducts with features of cholangiocyte differentiation. CCAs are classified anatomically into intrahepatic (iCCA), perihilar (pCCA), and distal CCA (dCCA). Each subtype has distinct risk factors, molecular pathogenesis, therapeutic options, and prognosis. CCA is an aggressive malignancy with a poor overall prognosis and median survival of less than 2years in patients with advanced disease. Potentially curative surgical treatment options are limited to the subset of patients with early-stage disease. Presently, the available systemic medical therapies for advanced or metastatic CCA have limited therapeutic efficacy. Molecular alterations define the differences in biological behavior of each CCA subtype. Recent comprehensive genetic analysis has better characterized the genomic and transcriptomic landscape of each CCA subtype. Promising candidates for targeted, personalized therapy have emerged, including potential driver fibroblast growth factor receptor (FGFR) gene fusions and somatic mutations in isocitrate dehydrogenase (IDH)1/2 in iCCA, protein kinase cAMP-activated catalytic subunit alpha (PRKACA) or beta (PRKACB) gene fusions in pCCA, and ELF3 mutations in dCCA/ampullary carcinoma. A precision genomic medicine approach is dependent on an enhanced understanding of driver mutations in each subtype and stratification of patients according to their genetic drivers. We review the current genomic landscape of CCA, the potentially actionable molecular aberrations in each CCA subtype, and the role of immunotherapy in CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"therapeutic yield photodynamic therapy hilar cholangiocarcinoma introduction hilar cholangiocarcinoma h ccc klatskin tumor continues present challenge poor survival rates appropriate biliary drainage crucial prevent severe lethal complications cholangitis liver abscesses h ccc sensitivity chemotherapy low photodynamic therapy using protoporphyrine x additional therapeutic option aim evaluate clinical benefit pdt palliative treatment regimes patients h ccc methods retrospective analysis 53 patients h ccc period 11 years overall survival technical aspects pdt analyzed special attentionwasdirectedtocomplicationratesassociated withpdt theresultswerecompared data patients h ccc treated biliary drainage without pdt results total 50 sessions pdt performed 25 patients control group consisted 28 patients groups differ regarding age gender mean number pdt 2 per patient ranging 1 8 numbers ercp higher patients receiving pdt 6 3 patients received biliary drainage 3 2 cases 15 25 pdt applied one hepatic duct 7 patients groups received concomitant chemotherapy either gemcitabine alone gemcitabine plus oxaliplatin themeanhospitalisationtimeofpatientswithandwithoutpdtwasnotdifferent 12 10 days cholangiosepsis appeared frequent pts pdt 3 patients vs 1 patient liverabscessoccurredonlyinthepdtgroup n 3 aphototoxicreactionoccurred one patient based kaplan meier statistics estimated overall survival 2fold higher pts receiving pdt 478 71 days compared patients without pdt 220 61 days conclusions discussion photodynamic therapy h ccc significantly improved survival spite high occurrence complications pdt given preference biliary drainage alone google scholar","probabilities":0.9799733,"Title":"Therapeutic Yield Of Photodynamic Therapy For Hilar Cholangiocarcinoma","Abstract":"Introduction: Hilar cholangiocarcinoma (H-CCC; Klatskin tumor) continues to present a challenge with poor survival rates. Appropriate biliary drainage is crucial to prevent from severe and lethal complications such as cholangitis and liver abscesses. As H-CCC sensitivity chemotherapy is low photodynamic therapy using protoporphyrine X is an additional therapeutic option. Aim: To evaluate the clinical benefit of PDT in palliative treatment regimes of patients with h-CCC. Methods: Retrospective analysis of 53 patients with H-CCC over a period of 11 years. Overall survival and technical aspects of PDT were analyzed. Special attentionwasdirectedtocomplicationratesassociated withPDT.Theresultswerecompared with data of patients with H-CCC who were treated with biliary drainage without PDT. Results: In total, 50 sessions of PDT were performed in 25 patients. The control group consisted of 28 Patients. The groups did not differ regarding age and gender. Mean number of PDT was 2 per patient ranging from 1 to 8. The numbers of ERCP was higher in patients receiving PDT (6±3) than in patients who received biliary drainage only (3±2). In most cases (15/25) PDT was only applied to one hepatic duct. 7 patients in both of the groups received concomitant chemotherapy with either gemcitabine alone or gemcitabine plus oxaliplatin.ThemeanhospitalisationtimeofpatientswithandwithoutPDTwasnotdifferent (12±10 days). Cholangiosepsis appeared more frequent in pts. with PDT (3 patients vs. 1 patient).LiverabscessoccurredonlyinthePDTgroup(n=3).Aphototoxicreactionoccurred only in one patient. Based on Kaplan Meier statistics the estimated overall survival was 2fold higher in pts. receiving PDT (478 ± 71 days) compared to patients without PDT (220 ±61 days). Conclusions and discussion: Photodynamic therapy for H-CCC significantly improved survival. In spite of the high occurrence of complications, PDT should be given the preference over biliary drainage alone.","Source":"Google Scholar","category":"HUMAN","training_data":"Therapeutic Yield Of Photodynamic Therapy For Hilar Cholangiocarcinoma Introduction: Hilar cholangiocarcinoma (H-CCC; Klatskin tumor) continues to present a challenge with poor survival rates. Appropriate biliary drainage is crucial to prevent from severe and lethal complications such as cholangitis and liver abscesses. As H-CCC sensitivity chemotherapy is low photodynamic therapy using protoporphyrine X is an additional therapeutic option. Aim: To evaluate the clinical benefit of PDT in palliative treatment regimes of patients with h-CCC. Methods: Retrospective analysis of 53 patients with H-CCC over a period of 11 years. Overall survival and technical aspects of PDT were analyzed. Special attentionwasdirectedtocomplicationratesassociated withPDT.Theresultswerecompared with data of patients with H-CCC who were treated with biliary drainage without PDT. Results: In total, 50 sessions of PDT were performed in 25 patients. The control group consisted of 28 Patients. The groups did not differ regarding age and gender. Mean number of PDT was 2 per patient ranging from 1 to 8. The numbers of ERCP was higher in patients receiving PDT (6±3) than in patients who received biliary drainage only (3±2). In most cases (15/25) PDT was only applied to one hepatic duct. 7 patients in both of the groups received concomitant chemotherapy with either gemcitabine alone or gemcitabine plus oxaliplatin.ThemeanhospitalisationtimeofpatientswithandwithoutPDTwasnotdifferent (12±10 days). Cholangiosepsis appeared more frequent in pts. with PDT (3 patients vs. 1 patient).LiverabscessoccurredonlyinthePDTgroup(n=3).Aphototoxicreactionoccurred only in one patient. Based on Kaplan Meier statistics the estimated overall survival was 2fold higher in pts. receiving PDT (478 ± 71 days) compared to patients without PDT (220 ±61 days). Conclusions and discussion: Photodynamic therapy for H-CCC significantly improved survival. In spite of the high occurrence of complications, PDT should be given the preference over biliary drainage alone. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"genomic characterization cholangiocarcinoma primary sclerosing cholangitis reveals novel therapeutic opportunities background aims lifetime risk biliary tract cancer btc primary sclerosing cholangitis psc exceeds 20 btc currently leading cause death psc patients open new avenues management aimed delineate novel clinically relevant genomic pathological features large panel psc associated btc psc btc approach results analysed formalin fixed paraffin embedded tumor tissue 186 psc btc patients 11 centers eight countries anatomical locations included performed tumor dna sequencing 42 clinically relevant genetic loci detect mutations translocations copy number variations along histomorphological immunohistochemical characterization irrespective anatomical localization psc btc exhibited uniform molecular histological characteristic similar extrahepatic cholangiocarcinoma detected high frequency genomic alterations typical extrahepatic cholangiocarcinoma e g tp53 35 5 kras 28 0 cdkn2a 14 5 smad4 11 3 well potentially druggable mutations e g her2 erbb2 found high frequency non typical non ductal histomorphological subtypes 55 2 usually rare btc precursor lesion intraductal papillary neoplasia 18 3 conclusion genomic alterations psc btc include significant number putative actionable therapeutic targets notably psc btc show distinct extrahepatic morpho molecular phenotype independent anatomical location tumor findings advance understanding psc associated cholangiocarcinogenesis provide strong incentives clinical trials test genome based personalized treatment strategies psc btc stn","probabilities":0.875,"Title":"Genomic Characterization Of Cholangiocarcinoma In Primary Sclerosing Cholangitis Reveals Novel Therapeutic Opportunities","Abstract":"Background & aims: Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) exceeds 20% and BTC is currently the leading cause of death in PSC patients. To open new avenues for management, we aimed to delineate novel and clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC). \r\n\r\n Approach & results: We analysed formalin fixed, paraffin embedded tumor tissue from 186 PSC-BTC patients from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations and copy number variations, along with histomorphological and immunohistochemical characterization. Irrespective of the anatomical localization, PSC-BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, e.g. TP53 (35.5%), KRAS (28.0%), CDKN2A (14.5%), and SMAD4 (11.3%), as well as potentially druggable mutations (e.g. HER2/ERBB2). We found a high frequency of non-typical/non-ductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%) CONCLUSION: Genomic alterations in PSC-BTC include a significant number of putative actionable therapeutic targets. Notably, PSC-BTC show a distinct extrahepatic morpho-molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC-associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome-based personalized treatment strategies in PSC-BTC.","Source":"STN","category":"ANIMAL","training_data":"Genomic Characterization Of Cholangiocarcinoma In Primary Sclerosing Cholangitis Reveals Novel Therapeutic Opportunities Background & aims: Lifetime risk of biliary tract cancer (BTC) in primary sclerosing cholangitis (PSC) exceeds 20% and BTC is currently the leading cause of death in PSC patients. To open new avenues for management, we aimed to delineate novel and clinically relevant genomic and pathological features of a large panel of PSC-associated BTC (PSC-BTC). \r\n\r\n Approach & results: We analysed formalin fixed, paraffin embedded tumor tissue from 186 PSC-BTC patients from 11 centers in eight countries with all anatomical locations included. We performed tumor DNA sequencing at 42 clinically relevant genetic loci to detect mutations, translocations and copy number variations, along with histomorphological and immunohistochemical characterization. Irrespective of the anatomical localization, PSC-BTC exhibited a uniform molecular and histological characteristic similar to extrahepatic cholangiocarcinoma. We detected a high frequency of genomic alterations typical of extrahepatic cholangiocarcinoma, e.g. TP53 (35.5%), KRAS (28.0%), CDKN2A (14.5%), and SMAD4 (11.3%), as well as potentially druggable mutations (e.g. HER2/ERBB2). We found a high frequency of non-typical/non-ductal histomorphological subtypes (55.2%) and of the usually rare BTC precursor lesion, intraductal papillary neoplasia (18.3%) CONCLUSION: Genomic alterations in PSC-BTC include a significant number of putative actionable therapeutic targets. Notably, PSC-BTC show a distinct extrahepatic morpho-molecular phenotype, independent of the anatomical location of the tumor. These findings advance our understanding of PSC-associated cholangiocarcinogenesis and provide strong incentives for clinical trials to test genome-based personalized treatment strategies in PSC-BTC. STN","prediction_labels":"ANIMAL"},{"cleaned":"ciap1 promotes proliferation migration prevents apoptosis gallbladder cancer vitro gallbladder cancer gbc demanding fatal disease ideal treatment inoperable patients recent reports determined tnf associated lymphatic metastasis gbc resistance tnf killing remains largely unexplored assay first found cellular inhibitor apoptosis ciap1 overexpressed gbc tissues roles promoting proliferation migration gbc vitro homology ciap2 gbc cell survives tnf toxicity tnf induced apoptosis first prevail follows reduction ciap1 give rise apoptosis even stimulation tnf importantly loss ciap1 enhanced tnf cycloheximide induced apoptosis higher activation statuses caspase 8 caspase 3 without induction complex response tnf reduction ciap1 caused suppression nuclear factor b nf b pathway inhibition transcription cell death regulator cellular flice like inhibitory protein c flip instead conclude ciap1 oncological protein abundant gbc tissues enhances proliferation immigration blocks tnf apoptosis nf b pathway vitro google scholar","probabilities":0.9467213,"Title":"Ciap1 Promotes Proliferation And Migration And Prevents Apoptosis In Gallbladder Cancer In Vitro","Abstract":"Gallbladder cancer (GBC) is a demanding fatal disease with no ideal treatment for inoperable patients. Recent reports have determined TNF-α associated lymphatic metastasis in GBC, while its resistance to TNF-α-killing remains largely unexplored. In this assay, we first found cellular inhibitor of apoptosis (cIAP1) overexpressed in GBC tissues and the roles in promoting the proliferation and migration of GBC in vitro as its homology cIAP2 does. Then how GBC cell survives TNF-α toxicity and TNF-α-induced apoptosis first prevail as follows. The reduction in cIAP1 does not give rise to apoptosis even with the stimulation of TNF-α. Importantly, the loss of cIAP1 enhanced TNF-α/cycloheximide-induced apoptosis in higher activation statuses of Caspase-8, Caspase-3 without the induction of Complex Ⅱ. In response to TNF-α, the reduction in cIAP1 caused the suppression in nuclear factor-κB (NF-κB) pathway and inhibition of transcription of cell death regulator cellular FLICE-like Inhibitory Protein (c-FLIP) instead. To conclude, cIAP1 is an oncological protein abundant in GBC tissues, which enhances proliferation and immigration and blocks TNF-α from apoptosis through NF-κB pathway in vitro.","Source":"Google Scholar","category":"ANIMAL","training_data":"Ciap1 Promotes Proliferation And Migration And Prevents Apoptosis In Gallbladder Cancer In Vitro Gallbladder cancer (GBC) is a demanding fatal disease with no ideal treatment for inoperable patients. Recent reports have determined TNF-α associated lymphatic metastasis in GBC, while its resistance to TNF-α-killing remains largely unexplored. In this assay, we first found cellular inhibitor of apoptosis (cIAP1) overexpressed in GBC tissues and the roles in promoting the proliferation and migration of GBC in vitro as its homology cIAP2 does. Then how GBC cell survives TNF-α toxicity and TNF-α-induced apoptosis first prevail as follows. The reduction in cIAP1 does not give rise to apoptosis even with the stimulation of TNF-α. Importantly, the loss of cIAP1 enhanced TNF-α/cycloheximide-induced apoptosis in higher activation statuses of Caspase-8, Caspase-3 without the induction of Complex Ⅱ. In response to TNF-α, the reduction in cIAP1 caused the suppression in nuclear factor-κB (NF-κB) pathway and inhibition of transcription of cell death regulator cellular FLICE-like Inhibitory Protein (c-FLIP) instead. To conclude, cIAP1 is an oncological protein abundant in GBC tissues, which enhances proliferation and immigration and blocks TNF-α from apoptosis through NF-κB pathway in vitro. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"clinicopathological correlation cancer stem cell markers oct 4 cd133 expression prognostic factor malignant lesions gallbladder immunohistochemical study background gallbladder cancer gbc frequent biliary tract cancer high morbidity poor prognosis shows early metastasis invasiveness reliable biomarkers available detection gbc progression aim investigate immunohistochemical expression oct 4 cd133 malignant nonneoplastic lesions gallbladder analyze clinical significance expressions related clinicopathological parameters settings design prospective case control study conducted medical college background materials methods total 103 cases gallbladder grouped malignant lesions n 48 nonneoplastic lesions simple epithelial hyperplasia n 35 chronic cholecystitis n 20 tissue samples evaluated expression oct 4 cd133 using immunohistochemistry effort elucidate correlation expressions clinicopathological parameters statistical analysis final score calculated multiplying intensity percentage positive cells scores 2 considered positive results significant positive correlation higher expression levels oct 4 cd133 observed malignant compared nonneoplastic lesions gallbladder p 0 0001 high expression oct 4 cd133 significantly associated tumor grading oct 4 p 0 04 cd133 p 0 02 staging oct 4 p 0 03 cd133 p 0 02 liver metastasis oct 4 p 0 01 cd133 p 0 007 significantly reduced survival observed high expression oct 4 p 0 002 significant correction observed cd 133 survival conclusion study revealed high expression level oct 4 may provide new insight prognosis disease terms clinical staging grade pubmed","probabilities":0.962963,"Title":"Clinicopathological correlation of cancer stem cell markers Oct-4 and CD133 expression as prognostic factor in malignant lesions of gallbladder: An immunohistochemical study","Abstract":"BACKGROUND: Gallbladder cancer (GBC) is the most frequent biliary tract cancer, with high morbidity and poor prognosis, and shows early metastasis and invasiveness. No reliable biomarkers are available for detection of GBC progression. AIM: To investigate the immunohistochemical expression of Oct-4 and CD133 in malignant and nonneoplastic lesions of gallbladder and to analyze the clinical significance of the expressions related to clinicopathological parameters. SETTINGS AND DESIGN: This is a prospective case control study, conducted in medical college background. MATERIALS AND METHODS: A total of 103 cases of gallbladder were grouped into malignant lesions (n = 48) and nonneoplastic lesions (simple epithelial hyperplasia; n = 35 and chronic cholecystitis; n = 20). All tissue samples were evaluated for expression of Oct-4 and CD133 using immunohistochemistry in an effort to elucidate the correlation between their expressions with clinicopathological parameters. STATISTICAL ANALYSIS: The final score was calculated by multiplying the intensity to the percentage of positive cells. The scores ≥2 were considered as positive. RESULTS: Significant positive correlation of higher expression levels of Oct-4 and CD133 were observed in malignant as compared to nonneoplastic lesions of gallbladder (P < 0.0001). High expression of Oct-4 and CD133 were significantly associated with tumor grading (Oct-4, P = 0.04; CD133, P = 0.02), staging (Oct-4, P = 0.03; CD133, P = 0.02), and liver metastasis (Oct-4, P = 0.01; CD133, P = 0.007). Significantly reduced survival was observed with high expression of Oct-4 (P = 0.002). No significant correction was observed between CD 133 and survival. CONCLUSION: This study revealed that high expression level of Oct-4 may provide a new insight for the prognosis of the disease in terms of clinical staging and grade.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological correlation of cancer stem cell markers Oct-4 and CD133 expression as prognostic factor in malignant lesions of gallbladder: An immunohistochemical study BACKGROUND: Gallbladder cancer (GBC) is the most frequent biliary tract cancer, with high morbidity and poor prognosis, and shows early metastasis and invasiveness. No reliable biomarkers are available for detection of GBC progression. AIM: To investigate the immunohistochemical expression of Oct-4 and CD133 in malignant and nonneoplastic lesions of gallbladder and to analyze the clinical significance of the expressions related to clinicopathological parameters. SETTINGS AND DESIGN: This is a prospective case control study, conducted in medical college background. MATERIALS AND METHODS: A total of 103 cases of gallbladder were grouped into malignant lesions (n = 48) and nonneoplastic lesions (simple epithelial hyperplasia; n = 35 and chronic cholecystitis; n = 20). All tissue samples were evaluated for expression of Oct-4 and CD133 using immunohistochemistry in an effort to elucidate the correlation between their expressions with clinicopathological parameters. STATISTICAL ANALYSIS: The final score was calculated by multiplying the intensity to the percentage of positive cells. The scores ≥2 were considered as positive. RESULTS: Significant positive correlation of higher expression levels of Oct-4 and CD133 were observed in malignant as compared to nonneoplastic lesions of gallbladder (P < 0.0001). High expression of Oct-4 and CD133 were significantly associated with tumor grading (Oct-4, P = 0.04; CD133, P = 0.02), staging (Oct-4, P = 0.03; CD133, P = 0.02), and liver metastasis (Oct-4, P = 0.01; CD133, P = 0.007). Significantly reduced survival was observed with high expression of Oct-4 (P = 0.002). No significant correction was observed between CD 133 and survival. CONCLUSION: This study revealed that high expression level of Oct-4 may provide a new insight for the prognosis of the disease in terms of clinical staging and grade. PubMed","prediction_labels":"HUMAN"},{"cleaned":"microbiological analysis bile patients benign malignant biliopancreatic diseases consequences background bactibilia several consequences human health objetive assessing bile microbiology patients biliopancreatic diseases order identify bacteria possible infectious complications methods retrospective study 30 bile culture samples patients benign malignant biliopancreatic diseases samples assessed set bile microbiological flora search possible link comorbidity carcinogenesis postoperative infectious complications results thirty bile samples patients mean age 57 7 years mostly female n 18 assessed bactibilia found 12 cases mostly patients benign diseases n 8 older 50 years n 23 female n 10 adenocarcinoma duodenal papilla n 9 cholelithiasis n 8 common diseases escherichia coli n 5 klebsiella sp n 3 predominantly found patients benign diseases klebsiella sp n 2 streptococcus sp n 2 prevalent cancer patients postoperative infectious complications seven cases five bactibilia associated patients p 0 084 conclusion bactibilia found 12 samples escherichia coli klebsiella sp often identified patients benign diseases well streptococcus sp klebsiella sp cancer patients trend higher postoperative infectious complication incidence patients bactibilia pubmed","probabilities":1.0,"Title":"MICROBIOLOGICAL ANALYSIS OF BILE IN PATIENTS WITH BENIGN AND MALIGNANT BILIOPANCREATIC DISEASES AND ITS CONSEQUENCES","Abstract":"BACKGROUND: Bactibilia has several consequences to human health. OBJETIVE: Assessing the bile microbiology of patients with biliopancreatic diseases in order to identify bacteria and their possible infectious complications. METHODS: Retrospective study of 30 bile culture samples from patients with benign and malignant biliopancreatic diseases. The samples were assessed to set the bile microbiological flora and to search for its possible link with comorbidity, carcinogenesis and postoperative infectious complications. RESULTS: Thirty bile samples from patients at mean age ≈57.7 years, mostly female (n=18), were assessed. Bactibilia was found in 12 cases, mostly in patients with benign diseases (n=8), older than 50 years (n=23) and female (n=10). Adenocarcinoma of the duodenal papilla (n=9) and cholelithiasis (n=8) were the most common diseases. Escherichia coli (n=5) and Klebsiella sp (n=3) were predominantly found in patients with benign diseases; and Klebsiella sp (n=2) and Streptococcus sp (n=2) were prevalent in cancer patients. There were postoperative infectious complications in seven cases, five of them in bactibilia-associated patients (P=0.084). CONCLUSION: Bactibilia was found in 12 samples and Escherichia coli and Klebsiella sp were most often identified in patients with benign diseases, as well as Streptococcus sp and Klebsiella sp in cancer patients. There was a trend of higher postoperative infectious complication incidence in patients with bactibilia.","Source":"PubMed","category":"ANIMAL","training_data":"MICROBIOLOGICAL ANALYSIS OF BILE IN PATIENTS WITH BENIGN AND MALIGNANT BILIOPANCREATIC DISEASES AND ITS CONSEQUENCES BACKGROUND: Bactibilia has several consequences to human health. OBJETIVE: Assessing the bile microbiology of patients with biliopancreatic diseases in order to identify bacteria and their possible infectious complications. METHODS: Retrospective study of 30 bile culture samples from patients with benign and malignant biliopancreatic diseases. The samples were assessed to set the bile microbiological flora and to search for its possible link with comorbidity, carcinogenesis and postoperative infectious complications. RESULTS: Thirty bile samples from patients at mean age ≈57.7 years, mostly female (n=18), were assessed. Bactibilia was found in 12 cases, mostly in patients with benign diseases (n=8), older than 50 years (n=23) and female (n=10). Adenocarcinoma of the duodenal papilla (n=9) and cholelithiasis (n=8) were the most common diseases. Escherichia coli (n=5) and Klebsiella sp (n=3) were predominantly found in patients with benign diseases; and Klebsiella sp (n=2) and Streptococcus sp (n=2) were prevalent in cancer patients. There were postoperative infectious complications in seven cases, five of them in bactibilia-associated patients (P=0.084). CONCLUSION: Bactibilia was found in 12 samples and Escherichia coli and Klebsiella sp were most often identified in patients with benign diseases, as well as Streptococcus sp and Klebsiella sp in cancer patients. There was a trend of higher postoperative infectious complication incidence in patients with bactibilia. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"long non coding rna anril overexpression predicts poor prognosis promotes metastasis proliferation perihilar cholangiocarcinoma abstract perihilar cholangiocarcinoma phcc still great challenge doctors aggressive feature poor survival rate molecular mechanisms phcc initiation progression remain obscure present accumulating evidence discovered long non coding rnas lncrnas crucial regulators cancer progression however functional role lncrnas phcc rarely reported present study found lncrna anril markedly overexpressed phcc cell lines clinical specimens compared normal human cholangiocyte cell line tumor adjacent tissues respectively statistical analysis phcc clinicopathological characteristics anril expression data found high anril expression correlated advanced tnm stage vascular invasion p 0 05 besides anril regulation investigated associated poor overall survival progression free survival phccs addition univariate multivariate cox regression analyses revealed high anril expression independent risk factor phcc poor prognosis anril regulation promoted migration invasion phcc cells transwell assay matrigel assay anril deficiency inhibited phcc cells metastasis moreover phcc cells anril overexpression exhibited obviously increased proliferation ability colony formation assay mtt assay however anril interference suppressed proliferation significantly conclusion anril promote phcc clinical progression proliferation metastasis lncrna anril may serve promising prognostic biomarker therapeutic target phcc google scholar","probabilities":0.9467213,"Title":"Long Non-Coding Rna Anril Overexpression Predicts Poor Prognosis And Promotes Metastasis And Proliferation In Perihilar Cholangiocarcinoma","Abstract":"Abstract: Perihilar cholangiocarcinoma (PHCC) is still a great challenge for doctors because of its aggressive feature and poor survival rate. The molecular mechanisms of PHCC initiation and progression remain obscure at present. Accumulating evidence discovered that long non-coding RNAs (lncRNAs) are crucial regulators in cancer progression. However, the functional role of lncRNAs in PHCC has been rarely reported. The present study found lncRNA ANRIL was markedly overexpressed in PHCC cell lines and clinical specimens compared with normal human cholangiocyte cell line and tumor adjacent tissues, respectively. Statistical analysis of PHCC clinicopathological characteristics with ANRIL expression data found that high ANRIL expression was correlated with advanced TNM stage and vascular invasion (P < 0.05). Besides, ANRIL up-regulation was investigated to be associated with poor overall survival and progression-free survival of PHCCs. In addition, both univariate and multivariate COX regression analyses revealed that high ANRIL expression was an independent risk factor of PHCC poor prognosis. ANRIL up-regulation promoted migration and invasion of PHCC cells on Transwell assay and Matrigel assay, while ANRIL deficiency inhibited PHCC cells metastasis. Moreover, PHCC cells with ANRIL overexpression exhibited obviously increased proliferation ability on Colony formation assay and MTT assay. However, ANRIL interference suppressed proliferation significantly. In conclusion, ANRIL could promote PHCC clinical progression, proliferation and metastasis. LncRNA ANRIL may serve as a promising prognostic biomarker and therapeutic target of PHCC","Source":"Google Scholar","category":"ANIMAL","training_data":"Long Non-Coding Rna Anril Overexpression Predicts Poor Prognosis And Promotes Metastasis And Proliferation In Perihilar Cholangiocarcinoma Abstract: Perihilar cholangiocarcinoma (PHCC) is still a great challenge for doctors because of its aggressive feature and poor survival rate. The molecular mechanisms of PHCC initiation and progression remain obscure at present. Accumulating evidence discovered that long non-coding RNAs (lncRNAs) are crucial regulators in cancer progression. However, the functional role of lncRNAs in PHCC has been rarely reported. The present study found lncRNA ANRIL was markedly overexpressed in PHCC cell lines and clinical specimens compared with normal human cholangiocyte cell line and tumor adjacent tissues, respectively. Statistical analysis of PHCC clinicopathological characteristics with ANRIL expression data found that high ANRIL expression was correlated with advanced TNM stage and vascular invasion (P < 0.05). Besides, ANRIL up-regulation was investigated to be associated with poor overall survival and progression-free survival of PHCCs. In addition, both univariate and multivariate COX regression analyses revealed that high ANRIL expression was an independent risk factor of PHCC poor prognosis. ANRIL up-regulation promoted migration and invasion of PHCC cells on Transwell assay and Matrigel assay, while ANRIL deficiency inhibited PHCC cells metastasis. Moreover, PHCC cells with ANRIL overexpression exhibited obviously increased proliferation ability on Colony formation assay and MTT assay. However, ANRIL interference suppressed proliferation significantly. In conclusion, ANRIL could promote PHCC clinical progression, proliferation and metastasis. LncRNA ANRIL may serve as a promising prognostic biomarker and therapeutic target of PHCC Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"incidental gallbladder carcinoma experience aim gallbladder carcinoma uncommon cancer poor prognosis era laparoscopic cholecistectomy treatment benign diseases incidental gallbladder carcinoma dramatically increased constitutes major way patients present gallbladder cancer allows detect cancer early stages better prognosis single center study report experience gallbladder carcinoma incidentally diagnosed laparoscopic colecistectomy performed cholelithiasis methods january 2003 december 2011 total 1193 patients underwent cholecistectomy general surgical unit iii university bari patients 458 males 735 females mean age 52 years range 19 91 6 1188 patients adenocarcinoma present pathologic specimens 0 5 results 1188 patients laparoscopic cholecistectomy attempted adenocarcinoma diagnosed histopathologically 6 cases 0 5 suspicion malignancy intraoperatively gallbladder wall appeared abnormal one patients frozen section analysis revealed adenocarcinoma remaining 5 cases routine histopathological studies revealed diagnosis gallbladder carcinoma one patient t1 tumor two t2 three t3 tumor conclusions present study rate incidental gallbladder carcinoma 0 5 according published english language literature risk factors widely related gallbladder cancer advanced age gallstones disease therapeutic approach gallbladder cancer applied according stage tumor study possible two patients t2 t3 tumor since high risk important comorbidities main causes refusal 3 patient 5 t1 patient underwent simple cholecystectomy similar reports single center study diagnosis incidental gallbladder carcinoma found 0 5 thus diagnosis gallbladder stones indication cholecystectomy google scholar","probabilities":0.9799733,"Title":"Incidental Gallbladder Carcinoma: Our Experience","Abstract":"Aim.\nGallbladder carcinoma is an uncommon cancer with a poor prognosis. In the era of laparoscopic cholecistectomy for treatment of benign diseases incidental gallbladder carcinoma has dramatically increased and now constitutes the major way patients present with gallbladder cancer and allows to detect cancer at early stages with a better prognosis. In this single-center study we report our experience with gallbladder carcinoma incidentally diagnosed during or after laparoscopic colecistectomy performed for cholelithiasis.\nMethods\nFrom January 2003 to December 2011 a total of 1193 patients underwent cholecistectomy at General Surgical Unit III of University of Bari. The patients were 458 males and 735 females, mean age was 52 years (range 19–91). In 6 of 1188 patients adenocarcinoma was present in the pathologic specimens (0,5%).\nResults\nOf 1188 patients in whom laparoscopic cholecistectomy was attempted adenocarcinoma was diagnosed histopathologically in 6 cases (0,5%). There was no suspicion of malignancy to any of them. Intraoperatively, gallbladder wall appeared abnormal in one patients and frozen section analysis revealed adenocarcinoma. In the remaining 5 cases routine histopathological studies revealed the diagnosis of gallbladder carcinoma. One patient had T1 tumor, two had T2 and three had T3 tumor.\nConclusions\nIn the present study the rate of incidental gallbladder carcinoma was 0,5%, according to the published English language literature. The risk factors widely related to the gallbladder cancer are advanced age and gallstones disease. The therapeutic approach to gallbladder cancer was applied according to the stage of tumor, but in our study this was possible only in two patients with T2 and T3 tumor since high risk and important comorbidities were the main causes for the refusal of 3 patient out of 5. Only the T1 patient underwent simple cholecystectomy. Similar to other reports in this single-center study the diagnosis of incidental gallbladder carcinoma was found to be of 0,5%, thus the diagnosis of gallbladder stones is an indication to the cholecystectomy.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidental Gallbladder Carcinoma: Our Experience Aim.\nGallbladder carcinoma is an uncommon cancer with a poor prognosis. In the era of laparoscopic cholecistectomy for treatment of benign diseases incidental gallbladder carcinoma has dramatically increased and now constitutes the major way patients present with gallbladder cancer and allows to detect cancer at early stages with a better prognosis. In this single-center study we report our experience with gallbladder carcinoma incidentally diagnosed during or after laparoscopic colecistectomy performed for cholelithiasis.\nMethods\nFrom January 2003 to December 2011 a total of 1193 patients underwent cholecistectomy at General Surgical Unit III of University of Bari. The patients were 458 males and 735 females, mean age was 52 years (range 19–91). In 6 of 1188 patients adenocarcinoma was present in the pathologic specimens (0,5%).\nResults\nOf 1188 patients in whom laparoscopic cholecistectomy was attempted adenocarcinoma was diagnosed histopathologically in 6 cases (0,5%). There was no suspicion of malignancy to any of them. Intraoperatively, gallbladder wall appeared abnormal in one patients and frozen section analysis revealed adenocarcinoma. In the remaining 5 cases routine histopathological studies revealed the diagnosis of gallbladder carcinoma. One patient had T1 tumor, two had T2 and three had T3 tumor.\nConclusions\nIn the present study the rate of incidental gallbladder carcinoma was 0,5%, according to the published English language literature. The risk factors widely related to the gallbladder cancer are advanced age and gallstones disease. The therapeutic approach to gallbladder cancer was applied according to the stage of tumor, but in our study this was possible only in two patients with T2 and T3 tumor since high risk and important comorbidities were the main causes for the refusal of 3 patient out of 5. Only the T1 patient underwent simple cholecystectomy. Similar to other reports in this single-center study the diagnosis of incidental gallbladder carcinoma was found to be of 0,5%, thus the diagnosis of gallbladder stones is an indication to the cholecystectomy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma joint cancer database analysis t1 tumor category divided t1a 5 cm t1b 5 cm tumor size 8th edition american joint committee cancer ajcc staging system intrahepatic cholangiocarcinoma icc aim present study investigate association tumor size prognosis patients t1 icc data regarding patients icc downloaded surveillance epidemiology end results database january 2004 december 2013 time first diagnosis entered database demographic pathological characteristics patients analyzed using independent test 2 test overall survival evaluated using kaplan meier analysis cut point tumor size determined using x tile software total 407 patients icc selected analysis including 199 cases stage ia 208 cases stage ib tumors independent prognostic factors patients stage ia icc age surgery independent prognostic factors patients stage ib icc included age surgery yes vs tumor size 5 7 vs 7 cm optimal cut value tumor size determined 7 cm using x tile software tumor size cut value 7 cm stratify patients risk better value 5 cm hazard ratio hr 1 775 95 confidence interval ci 1 356 2 323 hr 1 402 95 ci 1 078 1 824 respectively suggests t1 tumor category subclassified t1a t1b cut 7 cm rather 5 cm next edition ajcc staging system may take present evidence consideration improvement regarding accurate staging icc stn","probabilities":0.9799733,"Title":"Cholangiocarcinoma: A Joint Cancer Database Analysis","Abstract":"The T1 tumor category is further divided into T1a (≤5 cm) and T1b (>5 cm) by tumor size in the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to investigate the association between tumor size and prognosis in patients with T1 ICC. The data regarding patients with ICC was downloaded from the Surveillance, Epidemiology, and End Results database between January 2004 and December 2013, at the time of first diagnosis and entered into the database. Demographic and pathological characteristics of patients were analyzed using an independent t-test and χ2 test. Overall survival was evaluated using Kaplan-Meier analysis; the cut-off point for tumor size was determined using the X-tile software. A total of 407 patients with ICC were selected from the analysis, including 199 cases with stage IA and 208 cases with stage IB tumors. The independent prognostic factors for patients with stage IA ICC were age and surgery. Independent prognostic factors for patients with stage IB ICC included age, surgery (yes vs. no) and tumor size (5-7 vs. ≥7 cm). The optimal cut-off value for tumor size was determined to be ~7 cm using X-tile software. Tumor size with a cut-off value of 7 cm could stratify patients by risk better than a value of 5 cm [hazard ratio (HR), 1.775; 95% confidence interval (CI), 1.356-2.323 and; HR, 1.402; 95% CI, 1.078-1.824, respectively]. This suggests that the T1 tumor category should be subclassified into T1a and T1b with a cut-off of 7 cm rather than 5 cm. The next edition of the AJCC staging system may take the present evidence into consideration for improvement regarding the accurate staging of ICC.","Source":"STN","category":"HUMAN","training_data":"Cholangiocarcinoma: A Joint Cancer Database Analysis The T1 tumor category is further divided into T1a (≤5 cm) and T1b (>5 cm) by tumor size in the 8th edition of the American Joint Committee on Cancer (AJCC) staging system for intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to investigate the association between tumor size and prognosis in patients with T1 ICC. The data regarding patients with ICC was downloaded from the Surveillance, Epidemiology, and End Results database between January 2004 and December 2013, at the time of first diagnosis and entered into the database. Demographic and pathological characteristics of patients were analyzed using an independent t-test and χ2 test. Overall survival was evaluated using Kaplan-Meier analysis; the cut-off point for tumor size was determined using the X-tile software. A total of 407 patients with ICC were selected from the analysis, including 199 cases with stage IA and 208 cases with stage IB tumors. The independent prognostic factors for patients with stage IA ICC were age and surgery. Independent prognostic factors for patients with stage IB ICC included age, surgery (yes vs. no) and tumor size (5-7 vs. ≥7 cm). The optimal cut-off value for tumor size was determined to be ~7 cm using X-tile software. Tumor size with a cut-off value of 7 cm could stratify patients by risk better than a value of 5 cm [hazard ratio (HR), 1.775; 95% confidence interval (CI), 1.356-2.323 and; HR, 1.402; 95% CI, 1.078-1.824, respectively]. This suggests that the T1 tumor category should be subclassified into T1a and T1b with a cut-off of 7 cm rather than 5 cm. The next edition of the AJCC staging system may take the present evidence into consideration for improvement regarding the accurate staging of ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"comparison endoscopic bilateral metal stent drainage plastic stents palliation unresectable hilar biliary malignant strictures large multicenter study background endoscopic stenting manage malignant hilar biliary obstruction consensus regarding optimal stenting strategy multicenter study compared transpapillary parallel style bilateral metal stenting bilateral plastic stenting evaluated short long term outcomes methods recruited 262 consecutive patients bismuth classification types ii iv underwent either bilateral metal plastic stenting primary therapy four tertiary centers overcome selection bias performed 1 1 propensity score matching primary outcome overall survival results propensity score matching group comprised 96 patients significant differences baseline characteristics median survival significantly longer metal stenting group plastic stenting group 7 2 months 95 ci 6 0 8 5 vs 4 1 months 95 ci 2 9 5 3 p 0 015 clinical success rates significantly higher metal stenting group plastic stenting group 99 0 vs 71 9 respectively p 0 001 lower post procedure cholangitis incidence 7 3 vs 26 0 p 0 001 longer median symptom free stent patency 9 2 months 95 ci 7 6 10 6 vs 4 8 months 95 ci 4 2 5 3 p 0 001 fewer total interventions 1 3 0 6 vs 2 0 1 4 p 0 001 multivariate cox analysis overall survival metal stenting hr 0 589 p 0 002 hilar cholangiocarcinoma hr 0 419 p 0 009 adjuvant treatment hr 0 596 p 0 006 independent predictors death conclusions endoscopic therapy using bilateral metal stenting superior bilateral plastic stenting prolonged overall survival higher clinical success longer stent patency patients advanced hilar biliary malignancies stn","probabilities":0.9799733,"Title":"Comparison Of Endoscopic Bilateral Metal Stent Drainage With Plastic Stents In The Palliation Of Unresectable Hilar Biliary Malignant Strictures: A Large Multicenter Study","Abstract":"Background: Endoscopic stenting to manage malignant hilar biliary obstruction has no consensus regarding the optimal stenting strategy. In this multicenter study, we compared transpapillary parallel-style bilateral metal stenting with bilateral plastic stenting, and evaluated short- and long-term outcomes. \r\n\r\n Methods: We recruited 262 consecutive patients (Bismuth classification types II-IV) who underwent either bilateral metal or plastic stenting as primary therapy at four tertiary centers. To overcome selection bias, we performed 1:1 propensity score matching. Our primary outcome was overall survival. \r\n\r\n Results: After propensity score matching, each group comprised 96 patients, with no significant differences in any baseline characteristics. The median survival was significantly longer in the metal stenting group than in the plastic stenting group (7.2 months [95% CI 6.0-8.5] vs. 4.1 months [95% CI 2.9-5.3]; P = 0.015). The clinical success rates were significantly higher in the metal stenting group than in the plastic stenting group (99.0% vs. 71.9%, respectively; P < 0.001), and lower post-procedure cholangitis incidence (7.3% vs. 26.0%; P < 0.001), longer median symptom-free stent patency (9.2 months [95% CI 7.6-10.6] vs. 4.8 months [95% CI 4.2-5.3]; P < 0.001), and fewer total interventions (1.3 ± 0.6 vs. 2.0 ± 1.4; P < 0.001). In multivariate Cox analysis of the overall survival, metal stenting (HR 0.589, P = 0.002), hilar cholangiocarcinoma (HR 0.419, P = 0.009), and adjuvant treatment (HR 0.596, P = 0.006) were independent predictors of death. \r\n\r\n Conclusions: Endoscopic therapy using bilateral metal stenting is superior to bilateral plastic stenting, with prolonged overall survival, higher clinical success, and longer stent patency in patients with advanced hilar biliary malignancies.","Source":"STN","category":"HUMAN","training_data":"Comparison Of Endoscopic Bilateral Metal Stent Drainage With Plastic Stents In The Palliation Of Unresectable Hilar Biliary Malignant Strictures: A Large Multicenter Study Background: Endoscopic stenting to manage malignant hilar biliary obstruction has no consensus regarding the optimal stenting strategy. In this multicenter study, we compared transpapillary parallel-style bilateral metal stenting with bilateral plastic stenting, and evaluated short- and long-term outcomes. \r\n\r\n Methods: We recruited 262 consecutive patients (Bismuth classification types II-IV) who underwent either bilateral metal or plastic stenting as primary therapy at four tertiary centers. To overcome selection bias, we performed 1:1 propensity score matching. Our primary outcome was overall survival. \r\n\r\n Results: After propensity score matching, each group comprised 96 patients, with no significant differences in any baseline characteristics. The median survival was significantly longer in the metal stenting group than in the plastic stenting group (7.2 months [95% CI 6.0-8.5] vs. 4.1 months [95% CI 2.9-5.3]; P = 0.015). The clinical success rates were significantly higher in the metal stenting group than in the plastic stenting group (99.0% vs. 71.9%, respectively; P < 0.001), and lower post-procedure cholangitis incidence (7.3% vs. 26.0%; P < 0.001), longer median symptom-free stent patency (9.2 months [95% CI 7.6-10.6] vs. 4.8 months [95% CI 4.2-5.3]; P < 0.001), and fewer total interventions (1.3 ± 0.6 vs. 2.0 ± 1.4; P < 0.001). In multivariate Cox analysis of the overall survival, metal stenting (HR 0.589, P = 0.002), hilar cholangiocarcinoma (HR 0.419, P = 0.009), and adjuvant treatment (HR 0.596, P = 0.006) were independent predictors of death. \r\n\r\n Conclusions: Endoscopic therapy using bilateral metal stenting is superior to bilateral plastic stenting, with prolonged overall survival, higher clinical success, and longer stent patency in patients with advanced hilar biliary malignancies. STN","prediction_labels":"HUMAN"},{"cleaned":"early obesity risk cholangiocarcinoma united states background united states incidence intrahepatic cholangiocarcinoma icc increasing last decades despite public health problem obesity increasing incidence icc relationship early adulthood obesity icc never examined american population methods university texas md anderson cancer center conducted case control study aimed examining relationship icc history obesity controlling potential confounding several risk factors cases patients pathologically confirmed diagnosis icc controls healthy subjects recruited spouses patients md anderson cancers liver gastrointestinal case frequency matched 4 controls age 5 years sex race case patients controls interviewed risk factors liver cancer self reported weight body size pictogram ages 20 30 40 50 60 obtained participant 2016 recruited 63 newly diagnosed patients icc compared 252 healthy controls obesity defined body mass index bmi 30 0 results significant 3 fold increase icc risk obese individuals compared normal weight estimated odds ratio 95 confidence interval ci 3 3 1 3 9 1 p 02 obesity mid 20s mid 30s mid 40s significantly associated icc risk estimated 95 ci 7 3 2 8 19 7 7 2 4 20 9 4 8 2 11 4 respectively addition viral hepatitis heavy alcohol use 40 ml ethanol day family history cancer significantly associated icc underlying radiological pathological clinical evidence steatosis fibrosis cirrhosis significantly observed 25 icc patients early obesity conclusions concluded early adulthood obesity significant risk factor icc usa underlying fatty liver diseases significant factor icc progression integration obesity icc risk factors risk model may lead identify high risk individuals future collaboration us institutions highly warranted highlight mechanism obesity induced icc google scholar","probabilities":0.9799733,"Title":"Early Obesity And Risk Of Cholangiocarcinoma In The United States","Abstract":"Background: In the United States, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing over the last few decades. Despite the public health problem of obesity and the increasing incidence of ICC, the relationship between early adulthood obesity and ICC has never been examined in the American population. Methods: At the University of Texas MD Anderson Cancer Center we conducted a case-control study aimed at examining relationship between ICC and history of obesity after controlling for the potential confounding of several risk factors. Cases were patients with pathologically confirmed diagnosis of ICC. Controls were healthy subjects recruited from spouses of patients at MD Anderson who had cancers other than liver or gastrointestinal. Each case was frequency matched to 4 controls by age (± 5 years), sex, and race. Case patients and controls were interviewed for risk factors of liver cancer. A self-reported weight and body size pictogram at ages 20, 30, 40, 50, 60 was obtained from each participant. In 2016 we recruited 63 newly diagnosed patients with ICC who were compared to 252 healthy controls. Obesity was defined as body mass index (BMI) ≥ 30.0. Results: There was a significant 3 fold increase in ICC risk for obese individuals compared to those with normal weight. The estimated odds ratio (OR), 95%; confidence interval (CI) was 3.3 (1.3-9.1); P = .02. Obesity at the mid-20s, mid-30s, and mid- 40s was significantly associated with ICC risk; the estimated OR (95% CI) was 7.3 (2.8-19.7), 7 (2.4-20.9), and 4.8 (2-11.4), respectively. In addition, viral hepatitis, heavy alcohol use ( > 40 ml ethanol/day), and family history of cancer were significantly associated with ICC. Underlying radiological, pathological, or clinical evidence of steatosis, fibrosis, and cirrhosis was significantly observed in 25% ICC patients with early obesity. Conclusions: We concluded that early adulthood obesity is a significant risk factor for ICC in USA where underlying fatty liver diseases can be a significant factor for ICC progression. Integration of obesity with other ICC risk factors into a risk model may lead to identify high-risk individuals. Future collaboration with other US institutions is highly warranted to highlight the mechanism of obesity-induced ICC.","Source":"Google Scholar","category":"HUMAN","training_data":"Early Obesity And Risk Of Cholangiocarcinoma In The United States Background: In the United States, the incidence of intrahepatic cholangiocarcinoma (ICC) has been increasing over the last few decades. Despite the public health problem of obesity and the increasing incidence of ICC, the relationship between early adulthood obesity and ICC has never been examined in the American population. Methods: At the University of Texas MD Anderson Cancer Center we conducted a case-control study aimed at examining relationship between ICC and history of obesity after controlling for the potential confounding of several risk factors. Cases were patients with pathologically confirmed diagnosis of ICC. Controls were healthy subjects recruited from spouses of patients at MD Anderson who had cancers other than liver or gastrointestinal. Each case was frequency matched to 4 controls by age (± 5 years), sex, and race. Case patients and controls were interviewed for risk factors of liver cancer. A self-reported weight and body size pictogram at ages 20, 30, 40, 50, 60 was obtained from each participant. In 2016 we recruited 63 newly diagnosed patients with ICC who were compared to 252 healthy controls. Obesity was defined as body mass index (BMI) ≥ 30.0. Results: There was a significant 3 fold increase in ICC risk for obese individuals compared to those with normal weight. The estimated odds ratio (OR), 95%; confidence interval (CI) was 3.3 (1.3-9.1); P = .02. Obesity at the mid-20s, mid-30s, and mid- 40s was significantly associated with ICC risk; the estimated OR (95% CI) was 7.3 (2.8-19.7), 7 (2.4-20.9), and 4.8 (2-11.4), respectively. In addition, viral hepatitis, heavy alcohol use ( > 40 ml ethanol/day), and family history of cancer were significantly associated with ICC. Underlying radiological, pathological, or clinical evidence of steatosis, fibrosis, and cirrhosis was significantly observed in 25% ICC patients with early obesity. Conclusions: We concluded that early adulthood obesity is a significant risk factor for ICC in USA where underlying fatty liver diseases can be a significant factor for ICC progression. Integration of obesity with other ICC risk factors into a risk model may lead to identify high-risk individuals. Future collaboration with other US institutions is highly warranted to highlight the mechanism of obesity-induced ICC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"impact adjuvant chemotherapy survival patients intrahepatic cholangiocarcinoma multi institutional analysis background benefit adjuvant chemotherapy resected intrahepatic cholangiocarcinoma icc unclear aim current study investigate impact adjuvant chemotherapy survival among patients undergoing resection icc using multi institutional database methods 1154 icc patients undergoing curative intent hepatectomy 1990 2015 identified 14 institutions cox proportional hazard modeling used determine impact adjuvant chemotherapy overall survival os results following resection 347 30 patients received adjuvant chemotherapy commonly gemcitabine based regimen n 184 52 patients t2 t3 t4 disease likely receive adjuvant therapy compared patients t1a t1b disease 2 5 95 ci 1 89 3 23 p 0 001 among patients receive adjuvant therapy patients t2 t3 t4 tumors 5 year os 37 95 ci 28 9 44 4 versus 30 95 ci 23 8 35 6 respectively p 0 006 similarly patients n1 disease received adjuvant chemotherapy tended improved 5 year os 18 3 95 ci 9 0 30 1 vs adjuvant therapy 12 95 ci 3 9 24 4 p 0 050 conclusions adjuvant chemotherapy influence prognosis icc patients following surgical resection associated potential survival benefit subgroups patients increased risk recurrence advanced tumors pubmed","probabilities":0.9799733,"Title":"Impact of adjuvant chemotherapy on survival in patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis","Abstract":"BACKGROUND: The benefit of adjuvant chemotherapy for resected intrahepatic cholangiocarcinoma (ICC) is unclear. The aim of the current study was to investigate the impact of adjuvant chemotherapy on survival among patients undergoing resection of ICC using a multi-institutional database. METHODS: 1154 ICC patients undergoing curative-intent hepatectomy between 1990 and 2015 were identified from 14 institutions. Cox proportional hazard modeling was used to determine the impact of adjuvant chemotherapy on overall survival (OS). RESULTS: Following resection, 347 (30%) patients received adjuvant chemotherapy, most commonly a gemcitabine-based regimen (n = 184, 52%). Patients with T2/T3/T4 disease were more likely to receive adjuvant therapy compared with patients with T1a/T1b disease (OR 2.5, 95%CI 1.89-3.23; P < 0.001). Among patients who did and did not receive adjuvant therapy, patients with T2/T3/T4 tumors had a 5-year OS of 37% (95%CI 28.9-44.4) versus 30% (95%CI 23.8-35.6), respectively (p = 0.006). Similarly patients with N1 disease who received adjuvant chemotherapy tended to have improved 5-year OS (18.3%, 95%CI 9.0-30.1 vs. no adjuvant therapy 12%, 95%CI 3.9-24.4; P = 0.050). CONCLUSIONS: While adjuvant chemotherapy did not influence the prognosis of all ICC patients following surgical resection, it was associated with a potential survival benefit in subgroups of patients at increased risk for recurrence, such as those with advanced tumors.","Source":"PubMed","category":"HUMAN","training_data":"Impact of adjuvant chemotherapy on survival in patients with intrahepatic cholangiocarcinoma: a multi-institutional analysis BACKGROUND: The benefit of adjuvant chemotherapy for resected intrahepatic cholangiocarcinoma (ICC) is unclear. The aim of the current study was to investigate the impact of adjuvant chemotherapy on survival among patients undergoing resection of ICC using a multi-institutional database. METHODS: 1154 ICC patients undergoing curative-intent hepatectomy between 1990 and 2015 were identified from 14 institutions. Cox proportional hazard modeling was used to determine the impact of adjuvant chemotherapy on overall survival (OS). RESULTS: Following resection, 347 (30%) patients received adjuvant chemotherapy, most commonly a gemcitabine-based regimen (n = 184, 52%). Patients with T2/T3/T4 disease were more likely to receive adjuvant therapy compared with patients with T1a/T1b disease (OR 2.5, 95%CI 1.89-3.23; P < 0.001). Among patients who did and did not receive adjuvant therapy, patients with T2/T3/T4 tumors had a 5-year OS of 37% (95%CI 28.9-44.4) versus 30% (95%CI 23.8-35.6), respectively (p = 0.006). Similarly patients with N1 disease who received adjuvant chemotherapy tended to have improved 5-year OS (18.3%, 95%CI 9.0-30.1 vs. no adjuvant therapy 12%, 95%CI 3.9-24.4; P = 0.050). CONCLUSIONS: While adjuvant chemotherapy did not influence the prognosis of all ICC patients following surgical resection, it was associated with a potential survival benefit in subgroups of patients at increased risk for recurrence, such as those with advanced tumors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"factors affecting survival resection intrahepatic cholangiocarcinoma purpose study aimed assessing prognostic factors resection intrahepatic cholangiocarcinoma ihcc remain unclear methods among 70 patients ihcc admitted hospital 1998 2011 45 64 underwent resection 25 unresectable tumors univariate multivariate analyses conducted retrospectively assess factors influencing survival patients underwent resection results median survival times patients underwent resection versus 16 months versus 9 months respectively p 0 001 multivariate analysis identified residual tumor status relative risk 4 12 p 0 04 pathological differentiation relative risk 5 55 p 0 04 independent factors predicting survival patients underwent r1 resection significantly higher rate local recurrence underwent r0 resection p 0 008 r0 resection significant differences patterns rates recurrence patients narrow 5 mm versus wide 5 mm surgical margins conclusions r0 1 resection well differentiated tumor found independent prognostic factors long term survival ihcc resection r0 resection achieved width negative surgical margin affect patterns rates recurrence pubmed","probabilities":0.9799733,"Title":"Factors affecting survival after resection of intrahepatic cholangiocarcinoma","Abstract":"PURPOSE: This study aimed at assessing the prognostic factors of resection of intrahepatic cholangiocarcinoma (IHCC), which remain unclear. METHODS: Among 70 patients with IHCC, who were admitted to our hospital between 1998 and 2011, 45 (64 %) underwent resection and 25 had unresectable tumors. Univariate and multivariate analyses were conducted retrospectively to assess the factors influencing survival of the patients who underwent resection. RESULTS: The median survival times of the patients who underwent resection versus those who did not were 16 months versus 9 months, respectively (P < 0.001). Multivariate analysis identified residual tumor status (relative risk 4.12, P = 0.04) and pathological differentiation (relative risk 5.55, P = 0.04) as independent factors predicting survival. Patients who underwent R1 resection had a significantly higher rate of local recurrence than those who underwent R0 resection (P = 0.008). With R0 resection, there were no significant differences in patterns and rates of recurrence between patients with narrow (≤ 5 mm) versus wide (>5 mm) surgical margins. CONCLUSIONS: R0/1 resection and a well-differentiated tumor were found to be independent prognostic factors for long-term survival after IHCC resection. If R0 resection was achieved, the width of the negative surgical margin did not affect the patterns and rates of recurrence.","Source":"PubMed","category":"HUMAN","training_data":"Factors affecting survival after resection of intrahepatic cholangiocarcinoma PURPOSE: This study aimed at assessing the prognostic factors of resection of intrahepatic cholangiocarcinoma (IHCC), which remain unclear. METHODS: Among 70 patients with IHCC, who were admitted to our hospital between 1998 and 2011, 45 (64 %) underwent resection and 25 had unresectable tumors. Univariate and multivariate analyses were conducted retrospectively to assess the factors influencing survival of the patients who underwent resection. RESULTS: The median survival times of the patients who underwent resection versus those who did not were 16 months versus 9 months, respectively (P < 0.001). Multivariate analysis identified residual tumor status (relative risk 4.12, P = 0.04) and pathological differentiation (relative risk 5.55, P = 0.04) as independent factors predicting survival. Patients who underwent R1 resection had a significantly higher rate of local recurrence than those who underwent R0 resection (P = 0.008). With R0 resection, there were no significant differences in patterns and rates of recurrence between patients with narrow (≤ 5 mm) versus wide (>5 mm) surgical margins. CONCLUSIONS: R0/1 resection and a well-differentiated tumor were found to be independent prognostic factors for long-term survival after IHCC resection. If R0 resection was achieved, the width of the negative surgical margin did not affect the patterns and rates of recurrence. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance macrophage invasion hilar cholangiocarcinoma background tumor associated macrophages tams promote tumor progression effect survival human cancer however little known regarding influence tumor progression prognosis human hilar cholangiocarcinoma methods analyzed surgically resected tumor specimens hilar cholangiocarcinoma n 47 distribution localization tams defined expression cd68 abundance tams correlated clinicopathologic characteristics tumor recurrence patients survival statistical analysis performed using spss software results patients high density tams tumor invasive front tif showed significantly higher local overall tumor recurrence 0 05 furthermore high density tams associated decreased overall one year 83 6 vs 75 1 three year 61 3 vs 42 4 0 05 recurrence free survival one year 93 9 vs 57 4 three year 59 8 vs 26 2 0 05 tams tif tumor recurrence confirmed independent prognostic variables multivariate survival analysis 0 05 conclusions overall survival recurrence free survival patients hilar cholangiocarcinoma significantly improved patients low levels tams area tif compared high density tams observations suggest utilization valuable prognostic markers routine histopathologic evaluation might indicate future therapeutic approaches targeting tams pubmed","probabilities":0.8684211,"Title":"Prognostic significance of macrophage invasion in hilar cholangiocarcinoma","Abstract":"BACKGROUND: Tumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma. METHODS: We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software. RESULTS: Patients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6% vs. 75.1%; three-year 61.3% vs. 42.4%; both ρ < 0.05) and recurrence-free survival (one-year 93.9% vs. 57.4%; three-year 59.8% vs. 26.2%; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05). CONCLUSIONS: Overall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of macrophage invasion in hilar cholangiocarcinoma BACKGROUND: Tumor-associated macrophages (TAMs) promote tumor progression and have an effect on survival in human cancer. However, little is known regarding their influence on tumor progression and prognosis in human hilar cholangiocarcinoma. METHODS: We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution and localization of TAMs, as defined by expression of CD68. Abundance of TAMs was correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. Statistical analysis was performed using SPSS software. RESULTS: Patients with high density of TAMs in tumor invasive front (TIF) showed significantly higher local and overall tumor recurrence (both ρ < 0.05). Furthermore, high density of TAMs was associated with decreased overall (one-year 83.6% vs. 75.1%; three-year 61.3% vs. 42.4%; both ρ < 0.05) and recurrence-free survival (one-year 93.9% vs. 57.4%; three-year 59.8% vs. 26.2%; both ρ < 0.05). TAMs in TIF and tumor recurrence, were confirmed as the only independent prognostic variables in the multivariate survival analysis (all ρ < 0.05). CONCLUSIONS: Overall survival and recurrence free survival of patients with hilar cholangiocarcinoma significantly improved in patients with low levels of TAMs in the area of TIF, when compared to those with a high density of TAMs. These observations suggest their utilization as valuable prognostic markers in routine histopathologic evaluation, and might indicate future therapeutic approaches by targeting TAMs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radiofrequency ablation management unresectable intrahepatic cholangiocarcinoma purpose evaluate efficacy radiofrequency rf ablation treatment unresectable intrahepatic cholangiocarcinoma icc explore impact prognostic variables outcomes materials methods 2000 2010 17 patients 26 iccs underwent rf ablation single institution none patients surgery candidates seven patients 15 primary iccs 10 patients 11 recurrent iccs median largest diameter 4 4 cm range 2 1 6 8 cm percutaneous approach used 15 patients open approach used 2 patients early tumor necrosis recurrence free survival overall survival analyzed univariate analysis performed evaluate 12 clinicopathologic treatment related variables associated recurrence free survival overall survival results early tumor necrosis 96 2 25 26 tumors median follow period rf ablation 29 months median recurrence free survival overall survival 17 months 33 months 1 year 3 year 5 year survival rates 84 6 43 3 28 9 overall complication rate 3 6 1 28 sessions three variables found closely associated recurrence free survival lymph node metastases p 023 tumor differentiation p 034 tumor number p 035 variable significantly associated overall survival tumor differentiation p 033 conclusions preliminary results showed rf ablation may effective treatment icc achieved acceptable survival rate small population prognostic factors might allow better patient selection outcomes pubmed","probabilities":0.9799733,"Title":"Radiofrequency ablation in the management of unresectable intrahepatic cholangiocarcinoma","Abstract":"PURPOSE: To evaluate the efficacy of radiofrequency (RF) ablation for treatment of unresectable intrahepatic cholangiocarcinoma (ICC) and to explore the impact of prognostic variables on outcomes. MATERIALS AND METHODS: From 2000-2010, 17 patients with 26 ICCs underwent RF ablation at a single institution. None of the patients were surgery candidates. Seven patients had 15 primary ICCs, and 10 patients had 11 recurrent ICCs. The median largest diameter was 4.4 cm (range 2.1-6.8 cm). A percutaneous approach was used in 15 patients, and an open approach was used in 2 patients. Early tumor necrosis, recurrence-free survival, and overall survival were analyzed. Univariate analysis was performed to evaluate 12 clinicopathologic and treatment-related variables associated with recurrence-free survival and overall survival. RESULTS: Early tumor necrosis was 96.2% (25 of 26 tumors). The median follow-up period after RF ablation was 29 months. The median recurrence-free survival and overall survival were 17 months and 33 months. The 1-year, 3-year, and 5-year survival rates were 84.6%, 43.3%, and 28.9%, with an overall complication rate of 3.6% (1 of 28 sessions). Three variables were found to be closely associated with recurrence-free survival: lymph node metastases (P = .023), tumor differentiation (P = .034), and tumor number (P = .035). The only variable significantly associated with overall survival was tumor differentiation (P = .033). CONCLUSIONS: Preliminary results showed that RF ablation may be an effective treatment for ICC because it achieved an acceptable survival rate in a small population. Prognostic factors might allow better patient selection and outcomes.","Source":"PubMed","category":"HUMAN","training_data":"Radiofrequency ablation in the management of unresectable intrahepatic cholangiocarcinoma PURPOSE: To evaluate the efficacy of radiofrequency (RF) ablation for treatment of unresectable intrahepatic cholangiocarcinoma (ICC) and to explore the impact of prognostic variables on outcomes. MATERIALS AND METHODS: From 2000-2010, 17 patients with 26 ICCs underwent RF ablation at a single institution. None of the patients were surgery candidates. Seven patients had 15 primary ICCs, and 10 patients had 11 recurrent ICCs. The median largest diameter was 4.4 cm (range 2.1-6.8 cm). A percutaneous approach was used in 15 patients, and an open approach was used in 2 patients. Early tumor necrosis, recurrence-free survival, and overall survival were analyzed. Univariate analysis was performed to evaluate 12 clinicopathologic and treatment-related variables associated with recurrence-free survival and overall survival. RESULTS: Early tumor necrosis was 96.2% (25 of 26 tumors). The median follow-up period after RF ablation was 29 months. The median recurrence-free survival and overall survival were 17 months and 33 months. The 1-year, 3-year, and 5-year survival rates were 84.6%, 43.3%, and 28.9%, with an overall complication rate of 3.6% (1 of 28 sessions). Three variables were found to be closely associated with recurrence-free survival: lymph node metastases (P = .023), tumor differentiation (P = .034), and tumor number (P = .035). The only variable significantly associated with overall survival was tumor differentiation (P = .033). CONCLUSIONS: Preliminary results showed that RF ablation may be an effective treatment for ICC because it achieved an acceptable survival rate in a small population. Prognostic factors might allow better patient selection and outcomes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"low skeletal muscle density associated early death patients perihilar cholangiocarcinoma regardless subsequent treatment background low skeletal muscle mass associated increased postoperative morbidity worse survival following resection perihilar cholangiocarcinoma phc investigated predictive value skeletal muscle mass density overall survival os patients suspected phc regardless treatment methods baseline characteristics parameters regarding disease treatment collected patients phc 2002 2014 skeletal muscle mass density measured level third lumbar vertebra ct association skeletal muscle mass density os investigated using kaplan meier method cox survival results median os 233 included patients differ without low skeletal muscle mass p 0 203 whereas significantly different median os months observed patients low hr 7 0 95 ci 4 7 9 3 high hr 12 1 95 ci 8 1 16 1 skeletal muscle density p 0 004 low skeletal muscle density independently associated decreased os hr 1 78 95 ci 1 03 3 07 p 0 040 within first 6 months 6 months hr 0 68 95 ci 0 44 1 07 p 0 093 adjusting age tumour size suspected peritoneal distant metastases imaging conclusion time dependent effect skeletal muscle density os found patients phc regardless subsequent treatment low skeletal muscle density may identify patients risk early death stn","probabilities":0.9799733,"Title":"Low Skeletal Muscle Density Is Associated With Early Death In Patients With Perihilar Cholangiocarcinoma Regardless Of Subsequent Treatment","Abstract":"Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. \r\n\r\n Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. \r\n\r\n Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. \r\n\r\n Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death.","Source":"STN","category":"HUMAN","training_data":"Low Skeletal Muscle Density Is Associated With Early Death In Patients With Perihilar Cholangiocarcinoma Regardless Of Subsequent Treatment Background: Low skeletal muscle mass is associated with increased postoperative morbidity and worse survival following resection for perihilar cholangiocarcinoma (PHC). We investigated the predictive value of skeletal muscle mass and density for overall survival (OS) of all patients with suspected PHC, regardless of treatment. \r\n\r\n Methods: Baseline characteristics and parameters regarding disease and treatment were collected from all patients with PHC from 2002 to 2014. Skeletal muscle mass and density were measured at the level of the third lumbar vertebra on CT. The association between skeletal muscle mass and density with OS was investigated using the Kaplan-Meier method and Cox survival. \r\n\r\n Results: Median OS in 233 included patients did not differ between those with and without low skeletal muscle mass (p = 0.203), whereas a significantly different median OS (months) was observed between patients with low (HR 7.0, 95% CI 4.7-9.3) and high (HR 12.1, 95% CI 8.1-16.1) skeletal muscle density (p = 0.004). Low skeletal muscle density was independently associated with decreased OS (HR 1.78, 95% CI 1.03-3.07, p = 0.040) within the first 6 months but not after 6 months (HR 0.68, 95% CI 0.44-1.07, p = 0.093), after adjusting for age, tumour size and suspected peritoneal or other distant metastases on imaging. \r\n\r\n Conclusion: A time-dependent effect of skeletal muscle density on OS was found in patients with PHC, regardless of subsequent treatment. Low skeletal muscle density may identify patients at risk for early death. STN","prediction_labels":"HUMAN"},{"cleaned":"comparison anthropometric measurements adiposity relation cancer risk systematic review prospective studies purpose epidemiology relationship increased adiposity cancer risk long recognized however whether association measures abdominal whole body adiposity unclear aim systematic review compare cancer risk associated body mass index bmi indicator whole body adiposity indicators abdominal adiposity studies indicators directly measured methods conducted systematic search 1974 embase 1988 pubmed september 2015 keywords related adiposity cancer included studies limited cohort studies reporting directly measured anthropometry performing mutually adjusted analyses results thirteen articles identified two reporting breast cancer three colorectal cancer three endometrial cancer two gastro oesophageal cancer two renal cancer one ovarian cancer one bladder cancer one liver biliary tract cancer one leukaemia evidence suggests abdominal adiposity stronger predictor whole body adiposity gastro oesophageal leukaemia liver biliary tract cancer men women renal cancer women abdominal adiposity stronger predictor bladder colorectal cancer women bmi predictor men contrast bmi appears stronger predictor ovarian cancer breast endometrial cancer measures predictors cancer risk postmenopausal women conclusions studies used mutually adjusted measured anthropometric indicators studying adiposity cancer associations research investigating cancer risk adiposity include accurate non invasive indicators body fat deposition focus understudied cancer types namely leukaemia ovarian bladder liver biliary tract cancer pubmed","probabilities":0.9799733,"Title":"Comparison of anthropometric measurements of adiposity in relation to cancer risk: a systematic review of prospective studies","Abstract":"PURPOSE: In epidemiology, the relationship between increased adiposity and cancer risk has long been recognized. However, whether the association is the same for measures of abdominal or whole body adiposity is unclear. The aim of this systematic review is to compare cancer risk, associated with body mass index (BMI), an indicator of whole body adiposity, with indicators of abdominal adiposity in studies in which these indicators have been directly measured. METHODS: We conducted a systematic search from 1974 (EMBASE) and 1988 (PubMed) to September 2015 with keywords related to adiposity and cancer. Included studies were limited to cohort studies reporting directly measured anthropometry and performing mutually adjusted analyses. RESULTS: Thirteen articles were identified, with two reporting on breast cancer, three on colorectal cancer, three on endometrial cancer, two on gastro-oesophageal cancer, two on renal cancer, one on ovarian cancer, one on bladder cancer, one on liver and biliary tract cancer and one on leukaemia. Evidence suggests that abdominal adiposity is a stronger predictor than whole body adiposity for gastro-oesophageal, leukaemia and liver and biliary tract cancer in men and women and for renal cancer in women. Abdominal adiposity was a stronger predictor for bladder and colorectal cancer in women, while only BMI was a predictor in men. In contrast, BMI appears to be a stronger predictor for ovarian cancer. For breast and endometrial cancer, both measures were predictors for cancer risk in postmenopausal women. CONCLUSIONS: Only few studies used mutually adjusted and measured anthropometric indicators when studying adiposity-cancer associations. Further research investigating cancer risk and adiposity should include more accurate non-invasive indicators of body fat deposition and focus on the understudied cancer types, namely leukaemia, ovarian, bladder and liver and biliary tract cancer.","Source":"PubMed","category":"HUMAN","training_data":"Comparison of anthropometric measurements of adiposity in relation to cancer risk: a systematic review of prospective studies PURPOSE: In epidemiology, the relationship between increased adiposity and cancer risk has long been recognized. However, whether the association is the same for measures of abdominal or whole body adiposity is unclear. The aim of this systematic review is to compare cancer risk, associated with body mass index (BMI), an indicator of whole body adiposity, with indicators of abdominal adiposity in studies in which these indicators have been directly measured. METHODS: We conducted a systematic search from 1974 (EMBASE) and 1988 (PubMed) to September 2015 with keywords related to adiposity and cancer. Included studies were limited to cohort studies reporting directly measured anthropometry and performing mutually adjusted analyses. RESULTS: Thirteen articles were identified, with two reporting on breast cancer, three on colorectal cancer, three on endometrial cancer, two on gastro-oesophageal cancer, two on renal cancer, one on ovarian cancer, one on bladder cancer, one on liver and biliary tract cancer and one on leukaemia. Evidence suggests that abdominal adiposity is a stronger predictor than whole body adiposity for gastro-oesophageal, leukaemia and liver and biliary tract cancer in men and women and for renal cancer in women. Abdominal adiposity was a stronger predictor for bladder and colorectal cancer in women, while only BMI was a predictor in men. In contrast, BMI appears to be a stronger predictor for ovarian cancer. For breast and endometrial cancer, both measures were predictors for cancer risk in postmenopausal women. CONCLUSIONS: Only few studies used mutually adjusted and measured anthropometric indicators when studying adiposity-cancer associations. Further research investigating cancer risk and adiposity should include more accurate non-invasive indicators of body fat deposition and focus on the understudied cancer types, namely leukaemia, ovarian, bladder and liver and biliary tract cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical treatment intrahepatic cholangiocarcinoma despite surgical treatment intrahepatic cholangiocarcinoma icc becoming widely available prognosis hepatic resection icc remains poor icc relatively rare tnm staging system icc finally established 2000s resection margin status lymph node metastases important prognostic factors surgery icc however true impact wide resection margins lymph node dissection postoperative survival unclear although adjuvant chemotherapy improve postoperative prognosis patients various types cancer standard regimen developed icc 50 patients suffer postoperative recurrence even curative resection effective treatment recurrent icc established therefore despite advances imaging studies hepatobiliary surgery significant challenges remain improving prognosis patients icc pubmed","probabilities":0.9799733,"Title":"Surgical treatment for intrahepatic cholangiocarcinoma","Abstract":"Despite surgical treatment for intrahepatic cholangiocarcinoma (ICC) becoming more widely available, the prognosis after hepatic resection for ICC remains poor. Because ICC is relatively rare, the TNM staging system for ICC was finally established in the 2000s. Resection margin status and lymph node metastases are important prognostic factors after surgery for ICC; however, the true impact of wide resection margins or lymph node dissection on postoperative survival is unclear. Although adjuvant chemotherapy can improve the postoperative prognosis of patients with various types of cancer, no standard regimen has been developed for ICC. Over 50 % of patients suffer postoperative recurrence, even after curative resection, and no effective treatment for recurrent ICC has been established. Therefore, despite advances in imaging studies and hepatobiliary surgery, significant challenges remain in improving the prognosis of patients with ICC.","Source":"PubMed","category":"HUMAN","training_data":"Surgical treatment for intrahepatic cholangiocarcinoma Despite surgical treatment for intrahepatic cholangiocarcinoma (ICC) becoming more widely available, the prognosis after hepatic resection for ICC remains poor. Because ICC is relatively rare, the TNM staging system for ICC was finally established in the 2000s. Resection margin status and lymph node metastases are important prognostic factors after surgery for ICC; however, the true impact of wide resection margins or lymph node dissection on postoperative survival is unclear. Although adjuvant chemotherapy can improve the postoperative prognosis of patients with various types of cancer, no standard regimen has been developed for ICC. Over 50 % of patients suffer postoperative recurrence, even after curative resection, and no effective treatment for recurrent ICC has been established. Therefore, despite advances in imaging studies and hepatobiliary surgery, significant challenges remain in improving the prognosis of patients with ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"endoscopic radiofrequency ablation malignant biliary obstruction nationwide retrospective study 84 consecutive applications background biliary radiofrequency ablation rfa using habib endohbp catheter new endoscopic palliation therapy malignant biliary obstruction aim study assess feasibility safety technique methods nationwide retrospective study prospectively collected clinical data patients treated biliary rfa austria november 2010 december 2012 included procedure related complications adverse events within 30 days post intervention stent patency mortality rates investigated results total 58 patients 31 male 27 female median age 75 years underwent 84 rfa procedures 11 austrian referral centers biliary endoscopy predominant underlying condition klatskin tumor 45 58 cases 84 rfa procedures feasible without technical problems partial liver infarction induced rfa 49 year old klatskin tumor patient 30 days rfa procedure five cases cholangitis three cases hemobilia two cases cholangiosepsis one case gallbladder empyema hepatic coma newly diagnosed left bundle branch block occurred median stent patency last electively performed rfa 170 days 95 ci 63 277 almost significantly different metal plastic stenting 218 vs 115 days p 0 051 median survival 10 6 months 95 ci 6 9 14 4 time first rfa patient 17 9 months 95 ci 10 3 25 6 time initial diagnosis conclusions except one severe interventional complication hepatic infarct rfa presented technically feasible safe therapeutic option palliative treatment malignant biliary obstruction good results stent patency survival study proven prospective controlled trials quantify efficacy promising new technique pubmed","probabilities":0.9799733,"Title":"Endoscopic radiofrequency ablation for malignant biliary obstruction: a nationwide retrospective study of 84 consecutive applications","Abstract":"BACKGROUND: Biliary radiofrequency ablation (RFA) using the Habib™ EndoHBP catheter is a new endoscopic palliation therapy for malignant biliary obstruction. The aim of this study was to assess the feasibility and safety of this technique. METHODS: In this nationwide retrospective study of prospectively collected clinical data, all patients treated by biliary RFA in Austria between November 2010 and December 2012 were included. Procedure-related complications, adverse events within 30 days post-intervention, stent patency, and mortality rates were investigated. RESULTS: A total of 58 patients (31 male, 27 female, median age 75 years) underwent 84 RFA procedures at 11 Austrian referral centers for biliary endoscopy. The predominant underlying condition was Klatskin tumor (45 of 58 cases). All 84 RFA procedures were feasible without technical problems. A partial liver infarction was induced by RFA in a 49-year-old Klatskin tumor patient. During 30 days after each RFA procedure, five cases of cholangitis, three cases of hemobilia, two cases of cholangiosepsis, and one case each of gallbladder empyema, hepatic coma, and newly diagnosed left bundle branch block occurred. Median stent patency after last electively performed RFA was 170 days (95 % CI 63-277) and was almost significantly different between metal and plastic stenting (218 vs. 115 days; p = 0.051). Median survival was 10.6 months (95 % CI 6.9-14.4) from the time of the first RFA in each patient and 17.9 months (95 % CI 10.3-25.6) from the time of initial diagnosis. CONCLUSIONS: Except for one severe interventional complication (hepatic infarct), RFA presented as a technically feasible and safe therapeutic option for the palliative treatment of malignant biliary obstruction. The good results of stent patency and survival in this study should be proven in prospective (controlled) trials to further quantify the efficacy of this promising new technique.","Source":"PubMed","category":"HUMAN","training_data":"Endoscopic radiofrequency ablation for malignant biliary obstruction: a nationwide retrospective study of 84 consecutive applications BACKGROUND: Biliary radiofrequency ablation (RFA) using the Habib™ EndoHBP catheter is a new endoscopic palliation therapy for malignant biliary obstruction. The aim of this study was to assess the feasibility and safety of this technique. METHODS: In this nationwide retrospective study of prospectively collected clinical data, all patients treated by biliary RFA in Austria between November 2010 and December 2012 were included. Procedure-related complications, adverse events within 30 days post-intervention, stent patency, and mortality rates were investigated. RESULTS: A total of 58 patients (31 male, 27 female, median age 75 years) underwent 84 RFA procedures at 11 Austrian referral centers for biliary endoscopy. The predominant underlying condition was Klatskin tumor (45 of 58 cases). All 84 RFA procedures were feasible without technical problems. A partial liver infarction was induced by RFA in a 49-year-old Klatskin tumor patient. During 30 days after each RFA procedure, five cases of cholangitis, three cases of hemobilia, two cases of cholangiosepsis, and one case each of gallbladder empyema, hepatic coma, and newly diagnosed left bundle branch block occurred. Median stent patency after last electively performed RFA was 170 days (95 % CI 63-277) and was almost significantly different between metal and plastic stenting (218 vs. 115 days; p = 0.051). Median survival was 10.6 months (95 % CI 6.9-14.4) from the time of the first RFA in each patient and 17.9 months (95 % CI 10.3-25.6) from the time of initial diagnosis. CONCLUSIONS: Except for one severe interventional complication (hepatic infarct), RFA presented as a technically feasible and safe therapeutic option for the palliative treatment of malignant biliary obstruction. The good results of stent patency and survival in this study should be proven in prospective (controlled) trials to further quantify the efficacy of this promising new technique. PubMed","prediction_labels":"HUMAN"},{"cleaned":"influence marital status survival gallbladder cancer patients population based study marital status found prognostic factor survival various cancers role gallbladder cancer gbc fully studied study used surveillance epidemiology end results program seer registered database analyze survival gbc patients different marital status total 6 627 gbc patients selected seer database 2004 2013 age race grade histologic type ajcc stage seer stage marital status identified independent prognostic factors married gbc patients higher 5 year cancer specific survival css unmarried ones 20 1 v 17 8 p 0 05 subgroup analyses showed widowed patients 14 0 less 5 year css compared married ones stage 55 9 v 41 9 p 0 05 14 7 stage ii 15 6 v 10 9 p 0 05 1 5 stage iii iv 2 9 v 1 4 p 0 05 addition single independent prognostic factor stage iii iv hr 1 225 95 ci 1 054 1 423 p 0 008 results indicated widowed patients high risk cancer specific mortality marriage protective prognostic factor css pubmed","probabilities":0.9799733,"Title":"The influence of marital status on survival of gallbladder cancer patients: a population-based study","Abstract":"Marital status has been found to be a prognostic factor for survival in various cancers, but its role in gallbladder cancer (GBC) has not been fully studied. In this study, we used the Surveillance, Epidemiology, and End Results Program (SEER)-registered database to analyze the survival of GBC patients with different marital status. A total of 6,627 GBC patients were selected from SEER database from 2004 to 2013. The age, race, grade, histologic type, AJCC stage, SEER stage and marital status were identified as independent prognostic factors. Married GBC patients had a higher 5-year cancer-specific survival (CSS) than that of unmarried ones (20.1% v.s. 17.8%, P < 0.05). Subgroup analyses showed that widowed patients had 14.0% less of 5-year CSS compared to married ones of stage I (55.9% v.s. 41.9%, P < 0.05), 14.7% of stage II (15.6% v.s. 10.9%, P < 0.05), and 1.5% of stage III + IV (2.9% v.s. 1.4%, P < 0.05). In addition, single is an independent prognostic factor at stage III + IV (HR = 1.225, 95%CI 1.054-1.423, P = 0.008). These results indicated that widowed patients were at a high risk of cancer-specific mortality and marriage can be a protective prognostic factor in CSS.","Source":"PubMed","category":"HUMAN","training_data":"The influence of marital status on survival of gallbladder cancer patients: a population-based study Marital status has been found to be a prognostic factor for survival in various cancers, but its role in gallbladder cancer (GBC) has not been fully studied. In this study, we used the Surveillance, Epidemiology, and End Results Program (SEER)-registered database to analyze the survival of GBC patients with different marital status. A total of 6,627 GBC patients were selected from SEER database from 2004 to 2013. The age, race, grade, histologic type, AJCC stage, SEER stage and marital status were identified as independent prognostic factors. Married GBC patients had a higher 5-year cancer-specific survival (CSS) than that of unmarried ones (20.1% v.s. 17.8%, P < 0.05). Subgroup analyses showed that widowed patients had 14.0% less of 5-year CSS compared to married ones of stage I (55.9% v.s. 41.9%, P < 0.05), 14.7% of stage II (15.6% v.s. 10.9%, P < 0.05), and 1.5% of stage III + IV (2.9% v.s. 1.4%, P < 0.05). In addition, single is an independent prognostic factor at stage III + IV (HR = 1.225, 95%CI 1.054-1.423, P = 0.008). These results indicated that widowed patients were at a high risk of cancer-specific mortality and marriage can be a protective prognostic factor in CSS. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative gamma glutamyltransferase lymphocyte ratio predicts long term outcomes intrahepatic cholangiocarcinoma patients following hepatic resection background intrahepatic cholangiocarcinoma icc heterogeneous hepatobiliary cancer limited treatment options number studies illuminated relationship inflammation based prognostic scores outcomes patients icc however use reliable personalized prognostic algorithms icc resection pending aim assess prognostic value gamma glutamyltransferase lymphocyte ratio glr icc patients following curative resection methods icc patients following curative resection 2009 2017 divided two cohorts derivation cohort validation cohort derivation cohort used explore optimal cut value validation cohort used evaluate score overall survival os recurrence free survival rfs analyzed predictors os rfs determined results total 527 icc patients included randomly divided derivation cohort 264 patients validation cohort 263 patients two patient cohorts comparable baseline characteristics optimal cut value glr 33 7 kaplan meier curves showed worse os rfs glr 33 7 group compared glr 33 7 group cohorts univariate multivariate analysis results indicated glr independent prognostic factor os derivation cohort hazard ratio hr 1 620 95 confidence interval ci 1 066 2 462 p 0 024 validation cohort hr 1 466 95 ci 1 033 2 142 p 0 048 rfs derivation cohort hr 1 471 95 ci 1 029 2 103 p 0 034 validation cohort hr 1 480 95 ci 1 057 2 070 p 0 022 conclusion preoperative glr independent prognostic factor icc patients following hepatectomy high preoperative glr associated worse os rfs stn","probabilities":0.9799733,"Title":"Preoperative Gamma-Glutamyltransferase To Lymphocyte Ratio Predicts Long-Term Outcomes In Intrahepatic Cholangiocarcinoma Patients Following Hepatic Resection","Abstract":"Background: Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous hepatobiliary cancer with limited treatment options. A number of studies have illuminated the relationship between inflammation-based prognostic scores and outcomes in patients with ICC. However, the use of reliable and personalized prognostic algorithms in ICC after resection is pending. \r\n\r\n Aim: To assess the prognostic value of the gamma-glutamyltransferase to lymphocyte ratio (GLR) in ICC patients following curative resection. \r\n\r\n Methods: ICC patients following curative resection (2009-2017) were divided into two cohorts: The derivation cohort and validation cohort. The derivation cohort was used to explore an optimal cut-off value, and the validation cohort was used to further evaluate the score. Overall survival (OS) and recurrence-free survival (RFS) were analyzed, and predictors of OS and RFS were determined. \r\n\r\n Results: A total of 527 ICC patients were included and randomly divided into the derivation cohort (264 patients) and the validation cohort (263 patients). The two patient cohorts had comparable baseline characteristics. The optimal cut-off value for the GLR was 33.7. Kaplan-Meier curves showed worse OS and RFS in the GLR > 33.7 group compared with GLR ≤ 33.7 group in both cohorts. After univariate and multivariate analysis, the results indicated that GLR was an independent prognostic factor of OS [derivation cohort: hazard ratio (HR) = 1.620, 95% confidence interval (CI): 1.066-2.462, P = 0.024; validation cohort: HR = 1.466, 95%CI: 1.033-2.142, P = 0.048] and RFS [derivation cohort: HR = 1.471, 95%CI: 1.029-2.103, P = 0.034; validation cohort: HR = 1.480, 95%CI: 1.057-2.070, P = 0.022]. \r\n\r\n Conclusion: The preoperative GLR is an independent prognostic factor for ICC patients following hepatectomy. A high preoperative GLR is associated with worse OS and RFS.","Source":"STN","category":"HUMAN","training_data":"Preoperative Gamma-Glutamyltransferase To Lymphocyte Ratio Predicts Long-Term Outcomes In Intrahepatic Cholangiocarcinoma Patients Following Hepatic Resection Background: Intrahepatic cholangiocarcinoma (ICC) is a heterogeneous hepatobiliary cancer with limited treatment options. A number of studies have illuminated the relationship between inflammation-based prognostic scores and outcomes in patients with ICC. However, the use of reliable and personalized prognostic algorithms in ICC after resection is pending. \r\n\r\n Aim: To assess the prognostic value of the gamma-glutamyltransferase to lymphocyte ratio (GLR) in ICC patients following curative resection. \r\n\r\n Methods: ICC patients following curative resection (2009-2017) were divided into two cohorts: The derivation cohort and validation cohort. The derivation cohort was used to explore an optimal cut-off value, and the validation cohort was used to further evaluate the score. Overall survival (OS) and recurrence-free survival (RFS) were analyzed, and predictors of OS and RFS were determined. \r\n\r\n Results: A total of 527 ICC patients were included and randomly divided into the derivation cohort (264 patients) and the validation cohort (263 patients). The two patient cohorts had comparable baseline characteristics. The optimal cut-off value for the GLR was 33.7. Kaplan-Meier curves showed worse OS and RFS in the GLR > 33.7 group compared with GLR ≤ 33.7 group in both cohorts. After univariate and multivariate analysis, the results indicated that GLR was an independent prognostic factor of OS [derivation cohort: hazard ratio (HR) = 1.620, 95% confidence interval (CI): 1.066-2.462, P = 0.024; validation cohort: HR = 1.466, 95%CI: 1.033-2.142, P = 0.048] and RFS [derivation cohort: HR = 1.471, 95%CI: 1.029-2.103, P = 0.034; validation cohort: HR = 1.480, 95%CI: 1.057-2.070, P = 0.022]. \r\n\r\n Conclusion: The preoperative GLR is an independent prognostic factor for ICC patients following hepatectomy. A high preoperative GLR is associated with worse OS and RFS. STN","prediction_labels":"HUMAN"},{"cleaned":"immunohistochemical classification ampullary carcinomas critical reappraisal fails confirm prognostic relevance recently proposed panels highlights muc5ac strong prognosticator recently immunohistochemistry based classifications ampullary carcinomas proposed ang colleagues pmid 24832159 chang colleagues pmid 23439753 study prognostic value ang chang panel markers ck20 muc1 muc2 cdx2 well markers ck7 muc5ac muc6 tested full faced sections 136 ampullary carcinoma resections substantial 5 mm invasion immunohistochemistry correlated histologic classification intestinal int pancreatobiliary pb nontubular based 3 5 observer agreement clinical outcome prognostic correlation found muc1 cdx2 muc2 ck20 despite testing different quantitative cutoffs ck7 ck20 nonspecific ang classification reasonable correlation histologic subclassification tubular cases int versus pb high specificity low sensitivity ambiguous category large 29 included also classical cases prognostically ang classification approached reach statistical significance even large ambiguous group eliminated tubular cases analyzed ang int vs ang pb p 0 08 chang panel definition int subcategory clearly defined marginally reached prognostic significance tested muc1 cdx2 versus muc1 cdx2 wilcoxon test p 0 0485 31 cases unclassifiable individual marker found direct strong correlation clinical outcome muc5ac used ang chang panels statistically significant survival differences found various cutoffs tested 20 cutoff 5 y survival 68 vs 31 p 0 0002 addition muc5ac significantly stratified histologically pb int cases p 0 01 0 03 respectively well ang ambiguous chang unclassified cases p 0 006 0 007 respectively conclusion widely used putative lineage markers muc1 muc2 ck7 ck20 cdx2 seem direct significant prognostic correlation either individually combination ang chang panels ang panel helpful adjunct determining cell lineage caveats muc5ac proves significant independent prognosticator incorporated evaluation ampullary carcinomas pubmed","probabilities":0.962963,"Title":"Immunohistochemical Classification of Ampullary Carcinomas: Critical Reappraisal Fails to Confirm Prognostic Relevance for Recently Proposed Panels, and Highlights MUC5AC as a Strong Prognosticator","Abstract":"Recently, immunohistochemistry-based classifications of ampullary carcinomas have been proposed (Ang and colleagues [PMID: 24832159]; Chang and colleagues [PMID: 23439753]). In this study, the prognostic value of Ang/Chang panel markers (CK20, MUC1, MUC2, CDX2) as well as other markers (CK7, MUC5AC, and MUC6) were tested on full-faced sections of 136 ampullary carcinoma resections with substantial (>5 mm) invasion. Immunohistochemistry was correlated with both histologic classification (intestinal [INT], pancreatobiliary [PB], or nontubular based on ≥3/5 observer agreement) and clinical outcome. No prognostic correlation was found with MUC1, CDX2, MUC2 or CK20 despite testing with different quantitative cutoffs. CK7 and CK20 were nonspecific. Ang classification had reasonable correlation with histologic subclassification of tubular cases as INT versus PB with high specificity but low sensitivity and ambiguous category was large (29%) and included also some classical cases. Prognostically, Ang classification approached but did not reach statistical significance, even when their large \"ambiguous\" group was eliminated and only tubular cases were analyzed (Ang-INT vs. Ang-PB; P=0.08). The Chang panel, in which the definition of the INT subcategory is not clearly defined, only marginally reached prognostic significance when tested as MUC1+/CDX2- versus MUC1-/CDX2+ and only by Wilcoxon test (P=0.0485) but 31% of the cases were \"unclassifiable.\" The only individual marker that was found to have direct and strong correlation with the clinical outcome was MUC5AC (not used in the Ang or Chang panels), with statistically significant survival differences found with various cutoffs tested (for 20% cutoff, 5-y survival, 68% vs. 31%; P=0.0002). In addition, MUC5AC significantly stratified the histologically PB and INT cases (P=0.01 and 0.03, respectively), as well as Ang's ambiguous and Chang's unclassified cases (P=0.006 and 0.007, respectively). In conclusion, the widely used putative lineage markers, MUC1/MUC2/CK7/CK20/CDX2, do not seem to have direct/significant prognostic correlation either individually or in combination of Ang and Chang panels. Ang panel is helpful as an adjunct in determining the cell lineage with a few caveats. MUC5AC proves to be a significant independent prognosticator and should be incorporated into evaluation of ampullary carcinomas.","Source":"PubMed","category":"HUMAN","training_data":"Immunohistochemical Classification of Ampullary Carcinomas: Critical Reappraisal Fails to Confirm Prognostic Relevance for Recently Proposed Panels, and Highlights MUC5AC as a Strong Prognosticator Recently, immunohistochemistry-based classifications of ampullary carcinomas have been proposed (Ang and colleagues [PMID: 24832159]; Chang and colleagues [PMID: 23439753]). In this study, the prognostic value of Ang/Chang panel markers (CK20, MUC1, MUC2, CDX2) as well as other markers (CK7, MUC5AC, and MUC6) were tested on full-faced sections of 136 ampullary carcinoma resections with substantial (>5 mm) invasion. Immunohistochemistry was correlated with both histologic classification (intestinal [INT], pancreatobiliary [PB], or nontubular based on ≥3/5 observer agreement) and clinical outcome. No prognostic correlation was found with MUC1, CDX2, MUC2 or CK20 despite testing with different quantitative cutoffs. CK7 and CK20 were nonspecific. Ang classification had reasonable correlation with histologic subclassification of tubular cases as INT versus PB with high specificity but low sensitivity and ambiguous category was large (29%) and included also some classical cases. Prognostically, Ang classification approached but did not reach statistical significance, even when their large \"ambiguous\" group was eliminated and only tubular cases were analyzed (Ang-INT vs. Ang-PB; P=0.08). The Chang panel, in which the definition of the INT subcategory is not clearly defined, only marginally reached prognostic significance when tested as MUC1+/CDX2- versus MUC1-/CDX2+ and only by Wilcoxon test (P=0.0485) but 31% of the cases were \"unclassifiable.\" The only individual marker that was found to have direct and strong correlation with the clinical outcome was MUC5AC (not used in the Ang or Chang panels), with statistically significant survival differences found with various cutoffs tested (for 20% cutoff, 5-y survival, 68% vs. 31%; P=0.0002). In addition, MUC5AC significantly stratified the histologically PB and INT cases (P=0.01 and 0.03, respectively), as well as Ang's ambiguous and Chang's unclassified cases (P=0.006 and 0.007, respectively). In conclusion, the widely used putative lineage markers, MUC1/MUC2/CK7/CK20/CDX2, do not seem to have direct/significant prognostic correlation either individually or in combination of Ang and Chang panels. Ang panel is helpful as an adjunct in determining the cell lineage with a few caveats. MUC5AC proves to be a significant independent prognosticator and should be incorporated into evaluation of ampullary carcinomas. PubMed","prediction_labels":"HUMAN"},{"cleaned":"sulfated galactans red seaweed gracilaria fisheri target egfr inhibit cholangiocarcinoma cell proliferation cholangiocarcinoma cca increasing incidence worldwide resistant chemotherapeutic agents making treatment cca major challenge previous studies reported natural sulfated polysaccharides sps disrupted growth factor receptor activation cancer cells present study therefore aimed investigating antiproliferation effect sulfated galactans sg isolated red seaweed gracilaria fisheri g fisheri cca cell lines direct binding activity sg cca cells epidermal growth factor egf epidermal growth factor receptor egfr determined effect sg proliferation cca cells investigated cell cycle analyses expression signaling molecules associated proliferation also determined results demonstrated sg bound directly egfr sg inhibited proliferation various cca cell lines inhibiting egfr extracellular signal regulated kinases erk phosphorylation inhibited egf induced increased cell proliferation cell cycle analyses showed sg induced cell cycle arrest g0 g1 phase regulated cell cycle genes proteins cyclin d cyclin e cdk 4 cdk 2 regulated tumor suppressor protein p53 cyclin dependent kinase inhibitor p21 taken together data demonstrate sg g fisheri inhibited proliferation cca cells mechanism inhibition mediated extent inhibitory effects egfr activation egfr erk signaling pathway sg presents potential egfr targeted molecule may clinically developed combination therapy cca treatment stn","probabilities":0.9467213,"Title":"Sulfated Galactans From Red Seaweed Gracilaria Fisheri Target Egfr And Inhibit Cholangiocarcinoma Cell Proliferation","Abstract":"Cholangiocarcinoma (CCA) is increasing in incidence worldwide and is resistant to chemotherapeutic agents, making treatment of CCA a major challenge. Previous studies reported that natural sulfated polysaccharides (SPs) disrupted growth factor receptor activation in cancer cells. The present study, therefore, aimed at investigating the antiproliferation effect of sulfated galactans (SG) isolated from the red seaweed Gracilaria fisheri (G. fisheri) on CCA cell lines. Direct binding activity of SG to CCA cells, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) were determined. The effect of SG on proliferation of CCA cells was investigated. Cell cycle analyses and expression of signaling molecules associated with proliferation were also determined. The results demonstrated that SG bound directly to EGFR. SG inhibited proliferation of various CCA cell lines by inhibiting EGFR and extracellular signal-regulated kinases (ERK) phosphorylation, and inhibited EGF-induced increased cell proliferation. Cell cycle analyses showed that SG induced cell cycle arrest at the G0/G1 phase, down-regulated cell cycle genes and proteins (cyclin-D, cyclin-E, cdk-4, cdk-2), and up-regulated the tumor suppressor protein P53 and the cyclin-dependent kinase inhibitor P21. Taken together, these data demonstrate that SG from G. fisheri inhibited proliferation of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on EGFR activation and EGFR/ERK signaling pathway. SG presents a potential EGFR targeted molecule, which may be further clinically developed in a combination therapy for CCA treatment.","Source":"STN","category":"ANIMAL","training_data":"Sulfated Galactans From Red Seaweed Gracilaria Fisheri Target Egfr And Inhibit Cholangiocarcinoma Cell Proliferation Cholangiocarcinoma (CCA) is increasing in incidence worldwide and is resistant to chemotherapeutic agents, making treatment of CCA a major challenge. Previous studies reported that natural sulfated polysaccharides (SPs) disrupted growth factor receptor activation in cancer cells. The present study, therefore, aimed at investigating the antiproliferation effect of sulfated galactans (SG) isolated from the red seaweed Gracilaria fisheri (G. fisheri) on CCA cell lines. Direct binding activity of SG to CCA cells, epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) were determined. The effect of SG on proliferation of CCA cells was investigated. Cell cycle analyses and expression of signaling molecules associated with proliferation were also determined. The results demonstrated that SG bound directly to EGFR. SG inhibited proliferation of various CCA cell lines by inhibiting EGFR and extracellular signal-regulated kinases (ERK) phosphorylation, and inhibited EGF-induced increased cell proliferation. Cell cycle analyses showed that SG induced cell cycle arrest at the G0/G1 phase, down-regulated cell cycle genes and proteins (cyclin-D, cyclin-E, cdk-4, cdk-2), and up-regulated the tumor suppressor protein P53 and the cyclin-dependent kinase inhibitor P21. Taken together, these data demonstrate that SG from G. fisheri inhibited proliferation of CCA cells, and its mechanism of inhibition is mediated, to some extent, by inhibitory effects on EGFR activation and EGFR/ERK signaling pathway. SG presents a potential EGFR targeted molecule, which may be further clinically developed in a combination therapy for CCA treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"assessment nodal status ampullary carcinoma number positive lymph nodes versus lymph node ratio background study intended compare prognostic power number positive lymph nodes lymph node ratio patients ampullary carcinoma methods retrospective analysis conducted medical records 71 consecutive patients ampullary carcinoma underwent pancreaticoduodenectomy regional lymph node dissection total 2151 lymph nodes dissected median 28 nodes per patient examined histologically cutoff points determined number positive nodes lymph node ratio using 2 scores calculated cox proportional hazards regression model results lymph node metastasis found 34 patients best cutoff point number positive nodes identified three nodes lymph node ratio identified 10 univariate analysis revealed number positive nodes 0 1 3 4 p 0 0001 lymph node ratio 0 0 10 10 p 0 0001 significant prognostic factors multivariate analysis identified number positive nodes independent prognostic factor p 0 001 whereas lymph node ratio failed remain independent variable cumulative 5 year survival rates 85 patients 0 positive nodes 63 patients 1 3 positive nodes 0 patients 4 positive nodes p 0 0001 conclusions number positive lymph nodes better predicts outcome resection lymph node ratio patients ampullary carcinoma pubmed","probabilities":0.9799733,"Title":"Assessment of the nodal status in ampullary carcinoma: the number of positive lymph nodes versus the lymph node ratio","Abstract":"BACKGROUND: This study was intended to compare the prognostic power of the number of positive lymph nodes with that of the lymph node ratio in patients with ampullary carcinoma. METHODS: A retrospective analysis was conducted of the medical records of 71 consecutive patients with ampullary carcinoma who underwent pancreaticoduodenectomy with regional lymph node dissection. A total of 2151 lymph nodes were dissected (median: 28 nodes per patient) and examined histologically. Cutoff points were determined for both the number of positive nodes and the lymph node ratio using χ(2) scores calculated with the Cox proportional hazards regression model. RESULTS: Lymph node metastasis was found in 34 patients. The best cutoff point for the number of positive nodes was identified as three nodes, and that for the lymph node ratio was identified as 10%. Univariate analysis revealed both the number of positive nodes (0, 1-3, or ≥ 4; P < 0.0001) and the lymph node ratio (0%, 0-10%, or >10%; P < 0.0001) as significant prognostic factors. Multivariate analysis identified the number of positive nodes as an independent prognostic factor (P < 0.001), whereas the lymph node ratio failed to remain as an independent variable. The cumulative 5-year survival rates were 85% for patients with 0 positive nodes, 63% for patients with 1-3 positive nodes, and 0% for patients with ≥ 4 positive nodes (P < 0.0001). CONCLUSIONS: The number of positive lymph nodes better predicts the outcome after resection than the lymph node ratio in patients with ampullary carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Assessment of the nodal status in ampullary carcinoma: the number of positive lymph nodes versus the lymph node ratio BACKGROUND: This study was intended to compare the prognostic power of the number of positive lymph nodes with that of the lymph node ratio in patients with ampullary carcinoma. METHODS: A retrospective analysis was conducted of the medical records of 71 consecutive patients with ampullary carcinoma who underwent pancreaticoduodenectomy with regional lymph node dissection. A total of 2151 lymph nodes were dissected (median: 28 nodes per patient) and examined histologically. Cutoff points were determined for both the number of positive nodes and the lymph node ratio using χ(2) scores calculated with the Cox proportional hazards regression model. RESULTS: Lymph node metastasis was found in 34 patients. The best cutoff point for the number of positive nodes was identified as three nodes, and that for the lymph node ratio was identified as 10%. Univariate analysis revealed both the number of positive nodes (0, 1-3, or ≥ 4; P < 0.0001) and the lymph node ratio (0%, 0-10%, or >10%; P < 0.0001) as significant prognostic factors. Multivariate analysis identified the number of positive nodes as an independent prognostic factor (P < 0.001), whereas the lymph node ratio failed to remain as an independent variable. The cumulative 5-year survival rates were 85% for patients with 0 positive nodes, 63% for patients with 1-3 positive nodes, and 0% for patients with ≥ 4 positive nodes (P < 0.0001). CONCLUSIONS: The number of positive lymph nodes better predicts the outcome after resection than the lymph node ratio in patients with ampullary carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical parameters predicting survival duration hepatectomy intrahepatic cholangiocarcinoma background currently effective treatment intrahepatic cholangiocarcinoma icc complete hepatic tumour excision objective identify clinical parameters associated survival duration icc patients following hepatectomy construct mathematical model predicting survival duration methods demographic data clinical variables 102 patients diagnosed icc underwent exploratory laparotomy single centre july 1998 december 2000 followed average 24 months collected 2011 patients randomly assigned training n 76 validation n 26 groups univariate multivariate analyses performed identify factors associated posthepatectomy survival duration results univariate analysis revealed three lymph node metastases serum carbohydrate antigen 19 9 level greater 37 u ml stage iva tumours intra perihepatic metastases significantly associated decreased survival duration curative resection significantly associated increased survival duration mathematical model incorporating parameters age sex metastatic lymph node number curative surgery carbohydrate antigen 19 9 concentration alpha fetoprotein concentration hepatitis b tnm stage tumour differentiation constructed predicting survival duration survival duration less one year model exhibited 93 8 sensitivity 92 3 total accuracy positive predictive value 93 8 survival duration one three years corresponding values 80 0 69 2 57 1 respectively conclusions mathematical model presented current report prove useful clinical setting predicting extent curative resection affects survival icc patients selecting optimal postoperative treatment strategies pubmed","probabilities":0.9799733,"Title":"Clinical parameters predicting survival duration after hepatectomy for intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision. OBJECTIVE: To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration. METHODS: Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration. RESULTS: Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level greater than 37 U⁄mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, respectively. CONCLUSIONS: The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies.","Source":"PubMed","category":"HUMAN","training_data":"Clinical parameters predicting survival duration after hepatectomy for intrahepatic cholangiocarcinoma BACKGROUND: Currently, the most effective treatment for intrahepatic cholangiocarcinoma (ICC) is complete hepatic tumour excision. OBJECTIVE: To identify the clinical parameters associated with survival duration for ICC patients following hepatectomy, and to construct a mathematical model for predicting survival duration. METHODS: Demographic data and clinical variables for 102 patients diagnosed with ICC, who underwent exploratory laparotomy at a single centre from July 1998 to December 2000 and were followed for an average of 24 months, were collected in 2011. Patients were randomly assigned into training (n=76) and validation (n=26) groups. Univariate and multivariate analyses were performed to identify factors associated with posthepatectomy survival duration. RESULTS: Univariate analysis revealed that more than three lymph node metastases, a serum carbohydrate antigen 19-9 level greater than 37 U⁄mL, stage IVa tumours, and intra- or perihepatic metastases were significantly associated with decreased survival duration. Curative resection was significantly associated with increased survival duration. A mathematical model incorporating parameters of age, sex, metastatic lymph node number, curative surgery, carbohydrate antigen 19-9 concentration, alpha-fetoprotein concentration, hepatitis B, TNM stage and tumour differentiation was constructed for predicting survival duration. For a survival duration of less than one year, the model exhibited 93.8% sensitivity, 92.3% total accuracy and a positive predictive value of 93.8%; for a survival duration of one to three years, the corresponding values were 80.0%, 69.2% and 57.1%, respectively. CONCLUSIONS: The mathematical model presented in the current report should prove to be useful in the clinical setting for predicting the extent to which curative resection affects the survival of ICC patients, and for selecting optimal postoperative treatment strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"simple effective prognostic staging system based clinicopathologic features intrahepatic cholangiocarcinoma incidence mortality intrahepatic cholangiocarcinoma icc increasing however prognostic predictive system associated outcome surgery remains poorly defined study conducted retrospective survival analyses primary cohort 370 patients underwent partial hepatectomy icc 2005 2009 found seven variables significantly independent predictors overall survival os serum prealbumin hazard ratio hr 1 447 p 0 015 carbohydrate antigen 19 9 hr 1 438 p 0 009 carcinoembryonic antigen hr 1 732 p 0 002 tumor number hr 1 781 p 0 001 vascular invasion hr 1 784 p 0 001 regional lymphatic metastasis hr 2 003 p 0 001 local extrahepatic metastasis hr 1 506 p 0 008 using independent predictors created simple clinicopathologic prognostic staging system predicting survival icc patients resection validity prognostic staging system prospectively assessed 115 patients underwent partial hepatectomy january 2010 december 2010 institution prognostic power quantified using likelihood ratio test akaike information criteria compared 6 th 7 th ajcc staging systems new staging system primary cohort higher predictive accuracy os terms homogeneity discriminatory ability validation cohort homogeneity discrimination new staging system also superior two staging systems conclusions new staging system based clinicopathologic features may provide relatively higher accuracy prognostic prediction icc patients tumor resection stn","probabilities":0.9799733,"Title":"A Simple And Effective Prognostic Staging System Based On Clinicopathologic Features Of Intrahepatic Cholangiocarcinoma","Abstract":"Incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing. However, its prognostic predictive system associated with outcome after surgery remains poorly defined. In this study, we conducted retrospective survival analyses in a primary cohort of 370 patients who underwent partial hepatectomy for ICC (2005 and 2009). We found that seven variables were significantly independent predictors for overall survival (OS): serum prealbumin (hazard ratio [HR]: 1.447; p = 0.015), carbohydrate antigen 19-9 (HR: 1.438; p = 0.009), carcinoembryonic antigen (HR: 1.732; p = 0.002), tumor number (HR: 1.781; p < 0.001), vascular invasion (HR: 1.784; p < 0.001), regional lymphatic metastasis (HR: 2.003; p < 0.001) and local extrahepatic metastasis (HR: 1.506; p = 0.008). Using these independent predictors, we created a simple clinicopathologic prognostic staging system for predicting survival of ICC patients after resection. The validity of the prognostic staging system was prospectively assessed in 115 patients who underwent partial hepatectomy between January 2010 and December 2010 at the same institution. The prognostic power was quantified using likelihood ratio test and Akaike information criteria. Compared with the 6(th) and 7(th) AJCC staging systems, the new staging system in the primary cohort had a higher predictive accuracy for OS in terms of homogeneity and discriminatory ability. In the validation cohort, the homogeneity and discrimination of the new staging system were also superior to the two other staging systems. \r\n\r\n Conclusions: The new staging system based on clinicopathologic features may provide relatively higher accuracy in prognostic prediction for ICC patients after tumor resection.","Source":"STN","category":"HUMAN","training_data":"A Simple And Effective Prognostic Staging System Based On Clinicopathologic Features Of Intrahepatic Cholangiocarcinoma Incidence and mortality of intrahepatic cholangiocarcinoma (ICC) are increasing. However, its prognostic predictive system associated with outcome after surgery remains poorly defined. In this study, we conducted retrospective survival analyses in a primary cohort of 370 patients who underwent partial hepatectomy for ICC (2005 and 2009). We found that seven variables were significantly independent predictors for overall survival (OS): serum prealbumin (hazard ratio [HR]: 1.447; p = 0.015), carbohydrate antigen 19-9 (HR: 1.438; p = 0.009), carcinoembryonic antigen (HR: 1.732; p = 0.002), tumor number (HR: 1.781; p < 0.001), vascular invasion (HR: 1.784; p < 0.001), regional lymphatic metastasis (HR: 2.003; p < 0.001) and local extrahepatic metastasis (HR: 1.506; p = 0.008). Using these independent predictors, we created a simple clinicopathologic prognostic staging system for predicting survival of ICC patients after resection. The validity of the prognostic staging system was prospectively assessed in 115 patients who underwent partial hepatectomy between January 2010 and December 2010 at the same institution. The prognostic power was quantified using likelihood ratio test and Akaike information criteria. Compared with the 6(th) and 7(th) AJCC staging systems, the new staging system in the primary cohort had a higher predictive accuracy for OS in terms of homogeneity and discriminatory ability. In the validation cohort, the homogeneity and discrimination of the new staging system were also superior to the two other staging systems. \r\n\r\n Conclusions: The new staging system based on clinicopathologic features may provide relatively higher accuracy in prognostic prediction for ICC patients after tumor resection. STN","prediction_labels":"HUMAN"},{"cleaned":"combination intraoperative radiofrequency ablation surgical resection treatment cholangiocarcinoma feasibility long term survival purpose patients intrahepatic cholangiocarcinoma icc eligible surgical resection due advanced stage aimed evaluate feasibility local tumor control long term survival intraoperative radiofrequency ablation iorfa surgical resection treat unresectable intrahepatic cholangiocarcinoma icc methods 2009 2016 20 consecutive patients 12 primary icc 8 recurrent icc underwent curative iorfa hepatic resection surgically unresectable icc patients qualified undergo surgical resection due multiple lesions causing postoperative hepatic insufficiency undesirable tumor locations surgical resection percutaneous rfa 51 treated tumors mean 2 6 0 9 tumors patient 24 treated iorfa 27 surgically removed technical success effectiveness overall survival progression free survival pfs complications assessed retrospectively overall survival pfs rates estimated kaplan meier method results technical success effectiveness iorfa 100 overall survival rates 6 months 1 3 5 years 95 79 27 14 respectively median overall survival time 22 0 3 45 months pfs rates 6 months 1 3 5 years 70 33 13 13 respectively median pfs 9 0 1 68 months prognosis significantly worse patients recurrent icc patients primary icc one patient 5 major complications due iorfa liver abscess biliary stricture conclusion iorfa surgical resection feasible option icc cases amenable treatment surgical resection alone strategy provides acceptable local tumor control overall survival stn","probabilities":0.9799733,"Title":"Combination Of Intraoperative Radiofrequency Ablation And Surgical Resection For Treatment Of Cholangiocarcinoma: Feasibility And Long-Term Survival","Abstract":"PURPOSE Most patients with intrahepatic cholangiocarcinoma (ICC) are not eligible for surgical resection due to advanced stage. We aimed to evaluate the feasibility, local tumor control, and long-term survival of intraoperative radiofrequency ablation (IORFA) with surgical resection to treat unresectable intrahepatic cholangiocarcinoma (ICC). METHODS From 2009 to 2016, 20 consecutive patients (12 primary ICC, 8 recurrent ICC) underwent curative IORFA with hepatic resection for surgically unresectable ICC. Patients were not qualified to undergo surgical resection due to multiple lesions causing postoperative hepatic insufficiency and undesirable tumor locations for surgical resection or percutaneous RFA. Of the 51 treated tumors (mean, 2.6±0.9 tumors/patient), 24 were treated by IORFA and 27 were surgically removed. The technical success and effectiveness, overall survival, progression-free survival (PFS), and complications were assessed retrospectively. The overall survival and PFS rates were estimated by the Kaplan-Meier method. RESULTS The technical success and effectiveness of IORFA were 100%. The overall survival rates at 6 months, 1, 3, and 5 years were 95%, 79%, 27%, and 14%, respectively. The median overall survival time was 22.0±3.45 months. The PFS rates at 6 months, 1, 3, and 5 years were 70%, 33%, 13%, and 13%, respectively. The median PFS was 9.0±1.68 months. The prognosis was significantly worse for patients with recurrent ICC than for patients with primary ICC. One patient (5%) had major complications due to IORFA such as liver abscess and biliary stricture. CONCLUSION IORFA with surgical resection can be a feasible option for ICC cases that are not amenable to treatment with surgical resection alone. This strategy provides acceptable local tumor control and overall survival.","Source":"STN","category":"HUMAN","training_data":"Combination Of Intraoperative Radiofrequency Ablation And Surgical Resection For Treatment Of Cholangiocarcinoma: Feasibility And Long-Term Survival PURPOSE Most patients with intrahepatic cholangiocarcinoma (ICC) are not eligible for surgical resection due to advanced stage. We aimed to evaluate the feasibility, local tumor control, and long-term survival of intraoperative radiofrequency ablation (IORFA) with surgical resection to treat unresectable intrahepatic cholangiocarcinoma (ICC). METHODS From 2009 to 2016, 20 consecutive patients (12 primary ICC, 8 recurrent ICC) underwent curative IORFA with hepatic resection for surgically unresectable ICC. Patients were not qualified to undergo surgical resection due to multiple lesions causing postoperative hepatic insufficiency and undesirable tumor locations for surgical resection or percutaneous RFA. Of the 51 treated tumors (mean, 2.6±0.9 tumors/patient), 24 were treated by IORFA and 27 were surgically removed. The technical success and effectiveness, overall survival, progression-free survival (PFS), and complications were assessed retrospectively. The overall survival and PFS rates were estimated by the Kaplan-Meier method. RESULTS The technical success and effectiveness of IORFA were 100%. The overall survival rates at 6 months, 1, 3, and 5 years were 95%, 79%, 27%, and 14%, respectively. The median overall survival time was 22.0±3.45 months. The PFS rates at 6 months, 1, 3, and 5 years were 70%, 33%, 13%, and 13%, respectively. The median PFS was 9.0±1.68 months. The prognosis was significantly worse for patients with recurrent ICC than for patients with primary ICC. One patient (5%) had major complications due to IORFA such as liver abscess and biliary stricture. CONCLUSION IORFA with surgical resection can be a feasible option for ICC cases that are not amenable to treatment with surgical resection alone. This strategy provides acceptable local tumor control and overall survival. STN","prediction_labels":"HUMAN"},{"cleaned":"five year relative survival rate gallbladder cancer usa europe japan available stn","probabilities":0.9799733,"Title":"Five-Year Relative Survival Rate Of Gallbladder Cancer In The Usa Europe And Japan","Abstract":"Not Available","Source":"STN","category":"HUMAN","training_data":"Five-Year Relative Survival Rate Of Gallbladder Cancer In The Usa Europe And Japan Not Available STN","prediction_labels":"HUMAN"},{"cleaned":"gallbladder extrahepatic bile duct cancers americas incidence mortality patterns trends trends gallbladder cancer incidence mortality populations across americas provide insight shifting epidemiologic patterns current potential impact preventative curative programs estimates gallbladder extrahepatic bile duct cancer incidence mortality year 2018 extracted international agency research cancer iarc globocan database 185 countries recorded registry based incidence 13 countries extracted iarcs cancer incidence five continents series corresponding national deaths mortality database among females highest estimated incidence gallbladder extrahepatic bile duct cancer americas found bolivia 21 0 per 100 000 chile 11 7 peru 6 0 us highest incidence rates observed among hispanics 1 8 chilean population gallbladder cancer rates declined females males 1998 2012 rates dropped slightly canada costa rica us whites hispanics los angeles gallbladder cancer mortality rates also decreased across studied countries although rising trends observed colombia canada 2010 countries within southern central america tended higher proportion unspecified biliary tract cancers public health terms decline gallbladder cancer incidence mortality rates encouraging however slight increase mortality rates recent years colombia canada warrant attention higher proportions unspecified biliary tract cancers correspondingly higher mortality rates suggest rigorous pathology procedures may needed surgery stn","probabilities":0.9799733,"Title":"Gallbladder And Extrahepatic Bile Duct Cancers In The Americas: Incidence And Mortality Patterns And Trends","Abstract":"Trends in gallbladder cancer incidence and mortality in populations across the Americas can provide insight into shifting epidemiologic patterns and the current and potential impact of preventative and curative programs. Estimates of gallbladder and extrahepatic bile duct cancer incidence and mortality for the year 2018 were extracted from International Agency for Research on Cancer (IARC) GLOBOCAN database for 185 countries. Recorded registry-based incidence from 13 countries was extracted from IARCs Cancer Incidence in Five Continents series and corresponding national deaths from the WHO mortality database. Among females, the highest estimated incidence for gallbladder and extrahepatic bile duct cancer in the Americas were found in Bolivia (21.0 per 100,000), Chile (11.7) and Peru (6.0). In the US, the highest incidence rates were observed among Hispanics (1.8). In the Chilean population, gallbladder cancer rates declined in both females and males between 1998 and 2012. Rates dropped slightly in Canada, Costa Rica, US Whites and Hispanics in Los Angeles. Gallbladder cancer mortality rates also decreased across the studied countries, although rising trends were observed in Colombia and Canada after 2010. Countries within Southern and Central America tended to have a higher proportion of unspecified biliary tract cancers. In public health terms, the decline in gallbladder cancer incidence and mortality rates is encouraging. However, the slight increase in mortality rates during recent years in Colombia and Canada warrant further attention. Higher proportions of unspecified biliary tract cancers (with correspondingly higher mortality rates) suggest more rigorous pathology procedures may be needed after surgery.","Source":"STN","category":"HUMAN","training_data":"Gallbladder And Extrahepatic Bile Duct Cancers In The Americas: Incidence And Mortality Patterns And Trends Trends in gallbladder cancer incidence and mortality in populations across the Americas can provide insight into shifting epidemiologic patterns and the current and potential impact of preventative and curative programs. Estimates of gallbladder and extrahepatic bile duct cancer incidence and mortality for the year 2018 were extracted from International Agency for Research on Cancer (IARC) GLOBOCAN database for 185 countries. Recorded registry-based incidence from 13 countries was extracted from IARCs Cancer Incidence in Five Continents series and corresponding national deaths from the WHO mortality database. Among females, the highest estimated incidence for gallbladder and extrahepatic bile duct cancer in the Americas were found in Bolivia (21.0 per 100,000), Chile (11.7) and Peru (6.0). In the US, the highest incidence rates were observed among Hispanics (1.8). In the Chilean population, gallbladder cancer rates declined in both females and males between 1998 and 2012. Rates dropped slightly in Canada, Costa Rica, US Whites and Hispanics in Los Angeles. Gallbladder cancer mortality rates also decreased across the studied countries, although rising trends were observed in Colombia and Canada after 2010. Countries within Southern and Central America tended to have a higher proportion of unspecified biliary tract cancers. In public health terms, the decline in gallbladder cancer incidence and mortality rates is encouraging. However, the slight increase in mortality rates during recent years in Colombia and Canada warrant further attention. Higher proportions of unspecified biliary tract cancers (with correspondingly higher mortality rates) suggest more rigorous pathology procedures may be needed after surgery. STN","prediction_labels":"HUMAN"},{"cleaned":"antiproliferative apoptotic effects xanthohumol cholangiocarcinoma cholangiocarcinoma remains second prevalent hepatic neoplasm united states 5 year survival rate less 10 currently systemic therapy demonstrated efficacy therefore urgent need identification molecularly targeted compound remains notch signaling pathway shown dysregulated cholangiocarcinoma exhibiting hyperactivity also possibly mediating chemotherapeutic resistance analyzed effects xanthohumol prenylated chalcone cholangiocarcinoma proliferation utilizing human cholangiocarcinoma cell lines cclp1 sg 231 cc sw 1 gaining insight associated mechanism xanthohumol potently reduced cellular proliferation colony formation cell confluency three cell lines xanthohumol induced cell cycle arrest well apoptosis reduction cell cycle regulatory proteins well increase pro apoptotic markers cleaved poly adp ribose polymerase cleaved caspase 3 decrease anti apoptotic markers x linked inhibitor apoptosis survivin molecular level xanthohumol reduced notch1 akt expression step wise time dependent fashion notch1 reductions preceding akt additionally xanthohumol reduced cholangiocarcinoma growth cclp 1 sg 231 derived mice xenografts summary show xanthohumol significantly reduced cholangiocarcinoma growth notch1 akt signaling axis furthermore known pharmacokinetics bioavailability xn supports continued development treatment cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Antiproliferative And Apoptotic Effects Of Xanthohumol In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma remains the second most prevalent hepatic neoplasm in the United States with a 5-year survival rate of less than 10%. Currently, no systemic therapy has demonstrated efficacy. Therefore, an urgent need for the identification of molecularly targeted compound(s) remains. The Notch signaling pathway has been shown to be dysregulated in cholangiocarcinoma, exhibiting hyperactivity while also possibly mediating chemotherapeutic resistance. We analyzed the effects of xanthohumol, a prenylated chalcone, on cholangiocarcinoma proliferation utilizing human cholangiocarcinoma cell lines CCLP1, SG-231 and CC-SW-1 while gaining insight into the associated mechanism. Xanthohumol potently reduced cellular proliferation, colony formation, and cell confluency in all three cell lines. Xanthohumol induced cell cycle arrest as well as apoptosis through the reduction of cell cycle regulatory proteins as well as an increase in pro-apoptotic markers (cleaved poly ADP ribose polymerase, cleaved caspase-3) and a decrease in anti-apoptotic markers (X-linked inhibitor of apoptosis and survivin). At the molecular level, xanthohumol reduced Notch1 and AKT expression in a step-wise and time-dependent fashion, with Notch1 reductions preceding AKT. Additionally, xanthohumol reduced cholangiocarcinoma growth in both CCLP-1 and SG-231 derived mice xenografts. In summary, we show that xanthohumol significantly reduced cholangiocarcinoma growth through the Notch1/AKT signaling axis. Furthermore, known pharmacokinetics and bioavailability of XN supports continued development of treatment for cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Antiproliferative And Apoptotic Effects Of Xanthohumol In Cholangiocarcinoma Cholangiocarcinoma remains the second most prevalent hepatic neoplasm in the United States with a 5-year survival rate of less than 10%. Currently, no systemic therapy has demonstrated efficacy. Therefore, an urgent need for the identification of molecularly targeted compound(s) remains. The Notch signaling pathway has been shown to be dysregulated in cholangiocarcinoma, exhibiting hyperactivity while also possibly mediating chemotherapeutic resistance. We analyzed the effects of xanthohumol, a prenylated chalcone, on cholangiocarcinoma proliferation utilizing human cholangiocarcinoma cell lines CCLP1, SG-231 and CC-SW-1 while gaining insight into the associated mechanism. Xanthohumol potently reduced cellular proliferation, colony formation, and cell confluency in all three cell lines. Xanthohumol induced cell cycle arrest as well as apoptosis through the reduction of cell cycle regulatory proteins as well as an increase in pro-apoptotic markers (cleaved poly ADP ribose polymerase, cleaved caspase-3) and a decrease in anti-apoptotic markers (X-linked inhibitor of apoptosis and survivin). At the molecular level, xanthohumol reduced Notch1 and AKT expression in a step-wise and time-dependent fashion, with Notch1 reductions preceding AKT. Additionally, xanthohumol reduced cholangiocarcinoma growth in both CCLP-1 and SG-231 derived mice xenografts. In summary, we show that xanthohumol significantly reduced cholangiocarcinoma growth through the Notch1/AKT signaling axis. Furthermore, known pharmacokinetics and bioavailability of XN supports continued development of treatment for cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"combined vascular resection analysis prognostic factors hilar cholangiocarcinoma background hilar cholangiocarcinoma hcca devastating malignancy arising bifurcation hepatic duct whether combined vascular resection benefits hcca patients controversial study undertaken assess effect combined vascular resection hcca patients analyze prognostic factors methods clinical data 154 hcca patients treated january 2005 december 2012 retrospectively analyzed patients divided three groups based vascular resection without vascular resection portal vein resection alone hepatic artery resection survival complication rates compared among three groups multivariate analysis made determine prognostic factors results significant differences found survival complication rates among three groups p 0 05 multivariate analysis showed 3 factors related survival lymph node metastasis tumor size 2 5 cm positive resection margin conclusions vascular resection improved survival rate patients hcca involving hepatic artery portal vein lymph node metastasis tumor size 2 5 cm positive resection margin poor prognostic factors patients hcca pubmed","probabilities":0.9799733,"Title":"Combined vascular resection and analysis of prognostic factors for hilar cholangiocarcinoma","Abstract":"BACKGROUND: Hilar cholangiocarcinoma (HCCA) is a devastating malignancy arising from the bifurcation of the hepatic duct, whether combined vascular resection benefits HCCA patients is controversial. This study was undertaken to assess the effect of combined vascular resection in HCCA patients and to analyze the prognostic factors. METHODS: Clinical data of 154 HCCA patients who had been treated from January 2005 to December 2012 were retrospectively analyzed. The patients were divided into three groups based on vascular resection: those without vascular resection; those with portal vein resection alone and those with hepatic artery resection. The survival and complication rates were compared among the three groups. Multivariate analysis was made to determine prognostic factors. RESULTS: No significant differences were found in survival and complication rates among the three groups (P>0.05). Multivariate analysis showed that 3 factors were related to survival: lymph node metastasis, tumor size (>2.5 cm), and positive resection margin. CONCLUSIONS: Vascular resection improved the survival rate of patients with HCCA involving the hepatic artery or portal vein. Lymph node metastasis, tumor size (>2.5 cm) and positive resection margin were poor prognostic factors in patients with HCCA.","Source":"PubMed","category":"HUMAN","training_data":"Combined vascular resection and analysis of prognostic factors for hilar cholangiocarcinoma BACKGROUND: Hilar cholangiocarcinoma (HCCA) is a devastating malignancy arising from the bifurcation of the hepatic duct, whether combined vascular resection benefits HCCA patients is controversial. This study was undertaken to assess the effect of combined vascular resection in HCCA patients and to analyze the prognostic factors. METHODS: Clinical data of 154 HCCA patients who had been treated from January 2005 to December 2012 were retrospectively analyzed. The patients were divided into three groups based on vascular resection: those without vascular resection; those with portal vein resection alone and those with hepatic artery resection. The survival and complication rates were compared among the three groups. Multivariate analysis was made to determine prognostic factors. RESULTS: No significant differences were found in survival and complication rates among the three groups (P>0.05). Multivariate analysis showed that 3 factors were related to survival: lymph node metastasis, tumor size (>2.5 cm), and positive resection margin. CONCLUSIONS: Vascular resection improved the survival rate of patients with HCCA involving the hepatic artery or portal vein. Lymph node metastasis, tumor size (>2.5 cm) and positive resection margin were poor prognostic factors in patients with HCCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic role hepatoma derived growth factor solid tumors eastern asia systematic review meta analysis hepatoma derived growth factor hdgf novel jack trades cancer quantify prognostic impact biomarker assess consistent expression solid tumors comprehensive search strategy used search relevant literature updated october 3 2014 pubmed embase web science correlations hdgf expression clinicopathological features cancer prognosis analyzed pooled hrs ors derived random effects models twenty six studies primarily eastern asia covering 2 803 patients included analysis published past decade found hdgf overexpression significantly associated overall survival os hros 2 35 95 ci 2 04 2 71 p 0 001 disease free survival dfs hrdfs 2 25 95 ci 1 81 2 79 p 0 001 solid tumors especially non small cell lung cancer hepatocellular carcinoma cholangiocarcinoma cca moreover multivariate survival analysis showed hdgf overexpression independent predictor poor prognosis hros 2 41 95 ci 2 02 2 81 p 0 001 hrdfs 2 39 95 ci 1 77 3 24 p 0 001 addition hdgf overexpression significantly associated tumor category t3 4 versus t1 2 2 12 95 ci 1 17 3 83 p 0 013 lymph node status n versus n 2 37 95 ci 1 31 4 29 p 0 03 cca study provides comprehensive examination literature available association hdgf overexpression os dfs clinicopathological features solid tumors meta analysis results provide evidence hdgf may new indicator poor cancer prognosis considering limitations eligible studies large scale prospective trials must conducted clarify prognostic value hdgf predicting cancer survival pubmed","probabilities":0.962963,"Title":"Prognostic role of hepatoma-derived growth factor in solid tumors of Eastern Asia: a systematic review and meta- analysis","Abstract":"Hepatoma-derived growth factor (HDGF) is a novel jack-of-all-trades in cancer. Here we quantify the prognostic impact of this biomarker and assess how consistent is its expression in solid tumors. A comprehensive search strategy was used to search relevant literature updated on October 3, 2014 in PubMed, EMBASE and WEB of Science. Correlations between HDGF expression and clinicopathological features or cancer prognosis was analyzed. All pooled HRs or ORs were derived from random-effects models. Twenty-six studies, primarily in Eastern Asia, covering 2,803 patients were included in the analysis, all of them published during the past decade. We found that HDGF overexpression was significantly associated with overall survival (OS) (HROS=2.35, 95%CI=2.04-2.71, p<0.001) and disease free survival (DFS) (HRDFS=2.25, 95%CI =1.81-2.79, p<0.001) in solid tumors, especially in non-small cell lung cancer, hepatocellular carcinoma and cholangiocarcinoma (CCA). Moreover, multivariate survival analysis showed that HDGF overexpression was an independent predictor of poor prognosis (HROS=2.41, 95%CI: 2.02-2.81, p<0.001; HRDFS=2.39, 95%CI: 1.77-3.24, p<0.001). In addition, HDGF overexpression was significantly associated with tumor category (T3-4 versus T1-2, OR=2.12, 95%CI: 1.17-3.83, p=0.013) and lymph node status (N+ versus N-, OR=2.37, 95%CI: 1.31-4.29, p=0.03) in CCA. This study provides a comprehensive examination of the literature available on the association of HDGF overexpression with OS, DFS and some clinicopathological features in solid tumors. Meta-analysis results provide evidence that HDGF may be a new indicator of poor cancer prognosis. Considering the limitations of the eligible studies, other large-scale prospective trials must be conducted to clarify the prognostic value of HDGF in predicting cancer survival.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic role of hepatoma-derived growth factor in solid tumors of Eastern Asia: a systematic review and meta- analysis Hepatoma-derived growth factor (HDGF) is a novel jack-of-all-trades in cancer. Here we quantify the prognostic impact of this biomarker and assess how consistent is its expression in solid tumors. A comprehensive search strategy was used to search relevant literature updated on October 3, 2014 in PubMed, EMBASE and WEB of Science. Correlations between HDGF expression and clinicopathological features or cancer prognosis was analyzed. All pooled HRs or ORs were derived from random-effects models. Twenty-six studies, primarily in Eastern Asia, covering 2,803 patients were included in the analysis, all of them published during the past decade. We found that HDGF overexpression was significantly associated with overall survival (OS) (HROS=2.35, 95%CI=2.04-2.71, p<0.001) and disease free survival (DFS) (HRDFS=2.25, 95%CI =1.81-2.79, p<0.001) in solid tumors, especially in non-small cell lung cancer, hepatocellular carcinoma and cholangiocarcinoma (CCA). Moreover, multivariate survival analysis showed that HDGF overexpression was an independent predictor of poor prognosis (HROS=2.41, 95%CI: 2.02-2.81, p<0.001; HRDFS=2.39, 95%CI: 1.77-3.24, p<0.001). In addition, HDGF overexpression was significantly associated with tumor category (T3-4 versus T1-2, OR=2.12, 95%CI: 1.17-3.83, p=0.013) and lymph node status (N+ versus N-, OR=2.37, 95%CI: 1.31-4.29, p=0.03) in CCA. This study provides a comprehensive examination of the literature available on the association of HDGF overexpression with OS, DFS and some clinicopathological features in solid tumors. Meta-analysis results provide evidence that HDGF may be a new indicator of poor cancer prognosis. Considering the limitations of the eligible studies, other large-scale prospective trials must be conducted to clarify the prognostic value of HDGF in predicting cancer survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"recent advances regulation cholangiocarcinoma growth cholangiocarcinomas arise neoplastic transformation cholangiocytes line intra extrahepatic biliary epithelium symptoms usually present late course disease time relatively resistant chemotherapeutic agents difficult treat display poor prognosis relative rarity disease overall volume research molecular pathophysiology associated disease small compared prevalent tumors however incidence devastating cancer rise renewed efforts understand pathogenesis cholangiocarcinoma needed design novel therapeutic strategies combat disease review summarizes recent advances knowledge understanding cholangiocarcinoma highlights potential novel therapeutic strategies may prove useful treat deadly disease pubmed","probabilities":0.9799733,"Title":"Recent advances in the regulation of cholangiocarcinoma growth","Abstract":"Cholangiocarcinomas arise after the neoplastic transformation of the cholangiocytes that line the intra- and extrahepatic biliary epithelium. Symptoms usually do not present until late in the course of the disease, at which time they are relatively resistant to chemotherapeutic agents and as such are difficult to treat and display a poor prognosis. Because of the relative rarity of this disease, the overall volume of research into the molecular pathophysiology associated with this disease is small compared with other more prevalent tumors. However, the incidence of this devastating cancer is on the rise and renewed efforts to understand the pathogenesis of cholangiocarcinoma is needed to design novel therapeutic strategies to combat this disease. This review summarizes the recent advances into our knowledge and understanding of cholangiocarcinoma and highlights potential novel therapeutic strategies that may prove useful to treat this deadly disease.","Source":"PubMed","category":"HUMAN","training_data":"Recent advances in the regulation of cholangiocarcinoma growth Cholangiocarcinomas arise after the neoplastic transformation of the cholangiocytes that line the intra- and extrahepatic biliary epithelium. Symptoms usually do not present until late in the course of the disease, at which time they are relatively resistant to chemotherapeutic agents and as such are difficult to treat and display a poor prognosis. Because of the relative rarity of this disease, the overall volume of research into the molecular pathophysiology associated with this disease is small compared with other more prevalent tumors. However, the incidence of this devastating cancer is on the rise and renewed efforts to understand the pathogenesis of cholangiocarcinoma is needed to design novel therapeutic strategies to combat this disease. This review summarizes the recent advances into our knowledge and understanding of cholangiocarcinoma and highlights potential novel therapeutic strategies that may prove useful to treat this deadly disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment strategy incidental gallbladder carcinoma without excess insufficiency objective radical surgery essential favorable result patients gallbladder cancer point view treatment strategy incidental gallbladder carcinoma igbc significant issue however still controversial present study retrospectively analyzed clinicopathological features upon additional radical surgery without excess insufficiency igbc methods april 2000 july 2016 2 145 patients underwent cholecystectomy 19 cases accidentally diagnosed gallbladder cancer 0 88 operative clinicopathological factors associated prognosis evaluated results additional radical surgery performed 8 cases two t1 patients t1a m patient received cystic duct resection t1b mp patient liver bed resection lymphadenectomy six t2 ss patients cystic duct resection cystic duct resection lymphadenectomy cystic duct resection liver bed resection lymphadenectomy performed 2 cases three t2 patients without additional surgery one t3a patient died recurrence cases evidence recurrence far cases received additional liver bed resection margin gall bladder resection negative cancer cells patients survived without recurrence t1 t2 additional surgery cases showed significant better survival rate compared cases p 0 0181 conclusion t2 stage igbc additional radical surgery strongly recommended however additional liver bed resection necessary margin gall bladder resection negative cancer cells google scholar","probabilities":0.9799733,"Title":"The Treatment Strategy For Incidental Gallbladder Carcinoma Without Excess And Insufficiency","Abstract":"Objective: Radical surgery is essential for the favorable result in patients with gallbladder cancer. From this point of view, the treatment strategy for incidental gallbladder carcinoma (IGBC) is a significant issue, however, it is still controversial.\nThe present study retrospectively analyzed the clinicopathological features upon the additional radical surgery without excess and insufficiency for IGBC.\nMethods: From April 2000 to July 2016, 2,145 patients underwent cholecystectomy. In these, 19 cases were accidentally diagnosed as gallbladder cancer (0.88%). Operative and clinicopathological factors associated with prognosis were evaluated.\nResults: The additional radical surgery was performed in 8 cases. In two T1 patients, T1a (m) patient received cystic duct resection, and T1b (mp) patient did liver bed resection with lymphadenectomy. In six T2 (ss) patients, cystic duct resection, cystic duct resection with lymphadenectomy, and cystic duct resection with liver bed resection and lymphadenectomy performed in each 2 cases. Three T2 patients without additional surgery and one T3a patient died of recurrence. In the other cases, there is no evidence of recurrence so far. In the cases that received additional liver bed resection, the margin of gall bladder resection was negative for cancer cells. These patients survived without recurrence. T1 or T2 with additional surgery cases showed a significant better survival rate compared with the other cases (P = 0.0181).\nConclusion: In T2 stage IGBC, the additional radical surgery is strongly recommended. However, additional liver bed resection should not be necessary, if the margin of gall bladder resection is negative for cancer cells.","Source":"Google Scholar","category":"HUMAN","training_data":"The Treatment Strategy For Incidental Gallbladder Carcinoma Without Excess And Insufficiency Objective: Radical surgery is essential for the favorable result in patients with gallbladder cancer. From this point of view, the treatment strategy for incidental gallbladder carcinoma (IGBC) is a significant issue, however, it is still controversial.\nThe present study retrospectively analyzed the clinicopathological features upon the additional radical surgery without excess and insufficiency for IGBC.\nMethods: From April 2000 to July 2016, 2,145 patients underwent cholecystectomy. In these, 19 cases were accidentally diagnosed as gallbladder cancer (0.88%). Operative and clinicopathological factors associated with prognosis were evaluated.\nResults: The additional radical surgery was performed in 8 cases. In two T1 patients, T1a (m) patient received cystic duct resection, and T1b (mp) patient did liver bed resection with lymphadenectomy. In six T2 (ss) patients, cystic duct resection, cystic duct resection with lymphadenectomy, and cystic duct resection with liver bed resection and lymphadenectomy performed in each 2 cases. Three T2 patients without additional surgery and one T3a patient died of recurrence. In the other cases, there is no evidence of recurrence so far. In the cases that received additional liver bed resection, the margin of gall bladder resection was negative for cancer cells. These patients survived without recurrence. T1 or T2 with additional surgery cases showed a significant better survival rate compared with the other cases (P = 0.0181).\nConclusion: In T2 stage IGBC, the additional radical surgery is strongly recommended. However, additional liver bed resection should not be necessary, if the margin of gall bladder resection is negative for cancer cells. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"carcinogenic human liver fluke current status opisthorchis viverrini metacercariae nakhon ratchasima thailand background opisthorchis viverrini infection serious public health problem southeast asia associated number hepatobiliary diseases evidence strongly indicates liver fluke infection etiology cholangiocarcinoma objectives study aimed investigate opisthorchis viverrini metacercarial infection cyprinoid fish collected 32 districts nakhon ratchasima province northeastern thailand one year period february 2010 february 2011 methods cross sectional study conducted data collected pepsin hcl digestion stereomicroscope respectively analysis performed using spss windows version 12 0 results total 640 cyprinidae family fish including 5 species collected different study sites investigated o viverrini metacercariae infection rate 12 3 79 640 predominantly cyclocheilichthys armatus c repasson puntioplites proctzysron hampala macrolepitota hampala dispar respectively prevalence o viverrini metaceria nakhon ratchasima area 78 1 predominantly sida kiakham thale conclusion findings stress natural fish species rural communities still source o viverrini infection put local people risk therefore public awareness prevention campaigns urgently required pubmed","probabilities":0.75,"Title":"Carcinogenic human liver fluke: current status of Opisthorchis viverrini metacercariae in Nakhon Ratchasima, Thailand","Abstract":"BACKGROUND: Opisthorchis viverrini infection is a serious public-health problem in Southeast Asia. It is associated with a number of hepatobiliary diseases and the evidence strongly indicates that liver fluke infection is the etiology of cholangiocarcinoma. OBJECTIVES: This study aimed to investigate Opisthorchis viverrini metacercarial infection in cyprinoid fish collected from 32 districts of Nakhon Ratchasima province, Northeastern Thailand during one year period from February 2010 to February 2011. METHODS: A cross-sectional study was conducted, data being collected with pepsin-HCl digestion and stereomicroscope, respectively. Analysis was performed using SPSS Windows Version 12.0. RESULTS: A total of 640 Cyprinidae family fish including 5 species were collected from different study sites, and investigated for O. viverrini metacercariae. The infection rate was 12.3% (79/640), predominantly in Cyclocheilichthys armatus, C. repasson, Puntioplites proctzysron, Hampala macrolepitota and Hampala dispar, respectively. The prevalence of O. viverrini metaceria in Nakhon Ratchasima area was 78.1%, predominantly in Sida and KiaKham Thale So. CONCLUSION: This findings stress that natural fish species in rural communities are still a source of O viverrini infection and put local people at risk, therefore public awareness and prevention campaigns are urgently required.","Source":"PubMed","category":"ANIMAL","training_data":"Carcinogenic human liver fluke: current status of Opisthorchis viverrini metacercariae in Nakhon Ratchasima, Thailand BACKGROUND: Opisthorchis viverrini infection is a serious public-health problem in Southeast Asia. It is associated with a number of hepatobiliary diseases and the evidence strongly indicates that liver fluke infection is the etiology of cholangiocarcinoma. OBJECTIVES: This study aimed to investigate Opisthorchis viverrini metacercarial infection in cyprinoid fish collected from 32 districts of Nakhon Ratchasima province, Northeastern Thailand during one year period from February 2010 to February 2011. METHODS: A cross-sectional study was conducted, data being collected with pepsin-HCl digestion and stereomicroscope, respectively. Analysis was performed using SPSS Windows Version 12.0. RESULTS: A total of 640 Cyprinidae family fish including 5 species were collected from different study sites, and investigated for O. viverrini metacercariae. The infection rate was 12.3% (79/640), predominantly in Cyclocheilichthys armatus, C. repasson, Puntioplites proctzysron, Hampala macrolepitota and Hampala dispar, respectively. The prevalence of O. viverrini metaceria in Nakhon Ratchasima area was 78.1%, predominantly in Sida and KiaKham Thale So. CONCLUSION: This findings stress that natural fish species in rural communities are still a source of O viverrini infection and put local people at risk, therefore public awareness and prevention campaigns are urgently required. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"metabolic characteristics advanced biliary tract cancer using 18f fluorodeoxyglucose positron emission tomography clinical implications background advanced biliary tract cancer btc metabolic landscape evaluated 18 f fluorodeoxyglucose fdg positron emission tomography pet yet furthermore reports clinical implications metabolic features limited aimed evaluate metabolic features clinical relevance advanced btc using 18 f fdg pet patients methods consecutively enrolled patients advanced btc underwent 18 f fdg pet prior palliative chemotherapy 2003 2013 evaluated findings pet suv max number lesions organs fdg uptake pathologic findings clinical outcomes results total 106 patients enrolled 53 intrahepatic cholangiocarcinoma icc 7 extrahepatic btc 30 gallbladder cancer gb ca 16 ampulla vater cancer aov ca median suv max differed according primary origin icc 9 10 extrahepatic btc 5 90 gb ca 9 10 aov ca 6 37 p 008 histologic differentiation well differentiated 4 95 moderately differentiated 6 60 poorly differentiated 14 50 p 004 patients high metabolic group suv max 7 5 poorly differentiated histology organs lesions fdg uptake low metabolic group suv max 7 5 low metabolic group significantly longer os 11 4 vs 7 4 months p 007 pfs 6 6 vs 4 3 months p 024 high metabolic group multivariate analysis suv max significant prognostic factor overall survival os p 047 progression free survival pfs p 039 conclusion metabolic characteristics advanced btc differ according primary origin histology metabolic features prognostic factors os pfs advanced btc pubmed","probabilities":0.9799733,"Title":"Metabolic Characteristics of Advanced Biliary Tract Cancer Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Their Clinical Implications","Abstract":"BACKGROUND: In advanced biliary tract cancer (BTC), the metabolic landscape has not been evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) yet. Furthermore, reports of the clinical implications of these metabolic features are limited. We aimed to evaluate the metabolic features and their clinical relevance in advanced BTC using (18)F-FDG PET. PATIENTS AND METHODS: We consecutively enrolled patients with advanced BTC who underwent (18)F-FDG PET prior to palliative chemotherapy between 2003 and 2013. We evaluated the findings of PET, such as SUV(max), the number of lesions and organs with FDG uptake, pathologic findings, and clinical outcomes. RESULTS: A total of 106 patients were enrolled: (53 intrahepatic cholangiocarcinoma [ICC], 7 extrahepatic BTC, 30 gallbladder cancer [GB Ca], and 16 ampulla of Vater cancer [AoV Ca]). The median SUV(max) differed according to the primary origin (ICC, 9.10; extrahepatic BTC, 5.90; GB Ca, 9.10; and AoV Ca, 6.37; p = .008) and histologic differentiation (well differentiated, 4.95; moderately differentiated, 6.60; poorly differentiated, 14.50; p = .004). Patients in the high metabolic group (SUV(max) of ≥7.5) had more poorly differentiated histology and more organs and lesions with FDG uptake than did those in the low metabolic group (SUV(max) of <7.5). The low metabolic group had a significantly longer OS (11.4 vs. 7.4 months, p = .007) and PFS (6.6 vs. 4.3 months, p = .024) than high metabolic group. In multivariate analysis, SUV(max) was a significant prognostic factor for overall survival (OS; p = .047) and progression-free survival (PFS; p = .039). CONCLUSION: Metabolic characteristics of advanced BTC differ according to primary origin and histology. These metabolic features could be prognostic factors for OS and PFS in advanced BTC.","Source":"PubMed","category":"HUMAN","training_data":"Metabolic Characteristics of Advanced Biliary Tract Cancer Using 18F-Fluorodeoxyglucose Positron Emission Tomography and Their Clinical Implications BACKGROUND: In advanced biliary tract cancer (BTC), the metabolic landscape has not been evaluated by (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET) yet. Furthermore, reports of the clinical implications of these metabolic features are limited. We aimed to evaluate the metabolic features and their clinical relevance in advanced BTC using (18)F-FDG PET. PATIENTS AND METHODS: We consecutively enrolled patients with advanced BTC who underwent (18)F-FDG PET prior to palliative chemotherapy between 2003 and 2013. We evaluated the findings of PET, such as SUV(max), the number of lesions and organs with FDG uptake, pathologic findings, and clinical outcomes. RESULTS: A total of 106 patients were enrolled: (53 intrahepatic cholangiocarcinoma [ICC], 7 extrahepatic BTC, 30 gallbladder cancer [GB Ca], and 16 ampulla of Vater cancer [AoV Ca]). The median SUV(max) differed according to the primary origin (ICC, 9.10; extrahepatic BTC, 5.90; GB Ca, 9.10; and AoV Ca, 6.37; p = .008) and histologic differentiation (well differentiated, 4.95; moderately differentiated, 6.60; poorly differentiated, 14.50; p = .004). Patients in the high metabolic group (SUV(max) of ≥7.5) had more poorly differentiated histology and more organs and lesions with FDG uptake than did those in the low metabolic group (SUV(max) of <7.5). The low metabolic group had a significantly longer OS (11.4 vs. 7.4 months, p = .007) and PFS (6.6 vs. 4.3 months, p = .024) than high metabolic group. In multivariate analysis, SUV(max) was a significant prognostic factor for overall survival (OS; p = .047) and progression-free survival (PFS; p = .039). CONCLUSION: Metabolic characteristics of advanced BTC differ according to primary origin and histology. These metabolic features could be prognostic factors for OS and PFS in advanced BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"skeletal muscle depletion predict survival patients advanced biliary tract cancer undergoing palliative chemotherapy background prior study investigated dynamics body weight body muscle mass prognostic factor advanced biliary tract cancer btc patients undergoing palliative chemotherapy investigated whether low skeletal muscle mass affects survival patients btc co analysis body weight loss body mass index bmi results multivariate analysis low skeletal muscle mass diagnosis decreased smi chemotherapy p 0 008 p 0 001 respectively poor prognostic factors overall survival os subgroup analysis revealed low skeletal muscle mass patients overweight obese bmi 25 kg m2 showed worse os p 0 001 additionally patients decreased bmi smi chemotherapy worse os p 0 001 furthermore patients decreased smi shorter survival regardless change bmi however patients smi maintained chemotherapy decreased bmi effect survival p 0 576 materials methods consecutively enrolled 524 patients advanced btc received palliative chemotherapy 2003 2013 total muscle cross sectional area cm2 l3 level assessed computed tomography analyzed defined low skeletal muscle mass skeletal muscle index smi 48 5 cm2 m2 men 39 5 cm2 m2 women using roc curves conclusions low skeletal muscle mass obesity muscle depletion palliative chemotherapy meaningful prognostic factors advanced btc considering muscle depletion weight change help accurately predict prognoses patients btc stn","probabilities":0.9799733,"Title":"Skeletal Muscle Depletion To Predict Survival Of Patients With Advanced Biliary Tract Cancer Undergoing Palliative Chemotherapy","Abstract":"Background: No prior study has investigated the dynamics of body weight with body muscle mass as a prognostic factor in advanced biliary tract cancer (BTC) patients undergoing palliative chemotherapy. We investigated whether low skeletal muscle mass affects survival in patients with BTC, with a co-analysis of body weight loss and body mass index (BMI). \r\n\r\n Results: By multivariate analysis, low skeletal muscle mass at diagnosis and decreased SMI during chemotherapy (p = 0.008 and p < 0.001, respectively) were poor prognostic factors for overall survival (OS). Subgroup analysis revealed that low skeletal muscle mass patients who were overweight or obese (BMI ≥ 25 kg/m2) showed worse OS (p < 0.001). Additionally, patients with both decreased BMI and SMI during chemotherapy had worse OS (p < 0.001). Furthermore, patients with decreased SMI had shorter survival regardless of change in BMI. However, for patients with SMI maintained during chemotherapy, decreased BMI had no effect on survival (p = 0.576). \r\n\r\n Materials and methods: We consecutively enrolled 524 patients with advanced BTC who received palliative chemotherapy between 2003 and 2013. Total muscle cross-sectional area (cm2) at the L3 level assessed by computed tomography was analyzed. We defined low skeletal muscle mass as a skeletal muscle index (SMI) < 48.5 cm2/m2 (men) and < 39.5 cm2/m2 (women) using ROC curves. \r\n\r\n Conclusions: Low skeletal muscle mass, obesity and muscle depletion during palliative chemotherapy are meaningful prognostic factors in advanced BTC. Considering muscle depletion with weight change could help to more accurately predict prognoses of patients with BTC.","Source":"STN","category":"HUMAN","training_data":"Skeletal Muscle Depletion To Predict Survival Of Patients With Advanced Biliary Tract Cancer Undergoing Palliative Chemotherapy Background: No prior study has investigated the dynamics of body weight with body muscle mass as a prognostic factor in advanced biliary tract cancer (BTC) patients undergoing palliative chemotherapy. We investigated whether low skeletal muscle mass affects survival in patients with BTC, with a co-analysis of body weight loss and body mass index (BMI). \r\n\r\n Results: By multivariate analysis, low skeletal muscle mass at diagnosis and decreased SMI during chemotherapy (p = 0.008 and p < 0.001, respectively) were poor prognostic factors for overall survival (OS). Subgroup analysis revealed that low skeletal muscle mass patients who were overweight or obese (BMI ≥ 25 kg/m2) showed worse OS (p < 0.001). Additionally, patients with both decreased BMI and SMI during chemotherapy had worse OS (p < 0.001). Furthermore, patients with decreased SMI had shorter survival regardless of change in BMI. However, for patients with SMI maintained during chemotherapy, decreased BMI had no effect on survival (p = 0.576). \r\n\r\n Materials and methods: We consecutively enrolled 524 patients with advanced BTC who received palliative chemotherapy between 2003 and 2013. Total muscle cross-sectional area (cm2) at the L3 level assessed by computed tomography was analyzed. We defined low skeletal muscle mass as a skeletal muscle index (SMI) < 48.5 cm2/m2 (men) and < 39.5 cm2/m2 (women) using ROC curves. \r\n\r\n Conclusions: Low skeletal muscle mass, obesity and muscle depletion during palliative chemotherapy are meaningful prognostic factors in advanced BTC. Considering muscle depletion with weight change could help to more accurately predict prognoses of patients with BTC. STN","prediction_labels":"HUMAN"},{"cleaned":"predictors long term outcomes pancreatic cancer resection abstract aims increasing number complex pancreatic cancer resections study aimed assess long term outcomes identify factors predict mortality methods prospective database consecutive patients underwent pancreatic cancer resection 2008 2014 analysed patient procedural characteristics collected including age co morbidities tumour histopathology lymph node involvement superior mesenteric portal vein smv pv resection logistic regression analysis used correlate factors cause mortality long term mortality rates studied based tumour resection margins results total 80 patients 42 males median age 68 42 82 included study followed median time 6 4 11yrs resected malignancies included pancreatic adenocarcinoma n 43 ampullary adenocarcinoma n 27 cholangiocarcinoma n 10 1 3 5yr mortality 5 40 56 respectively pancreatic adenocarcinoma 11 22 27 respectively ampullary adenocarcinoma 10 60 80 respectively cholangiocarcinoma 5yr survival rate higher ampullary cancer group p 0 01 smv pv resection 1 28 0 2 8 4 p 0 02 lymph node involvement 0 33 0 98 1 09 p 0 04 cancer recurrence 0 1 0 03 0 34 p 0 0001 independent factors predictive long term mortality disease free tumour margins showed higher survival rate p 0 005 evident ampullary adenocarcinomas p 0 007 conclusions ampullary adenocarcinomas associated better long term survival smv pv resection lymph node involvement cancer recurrence strongest predictors long term mortality pancreatic cancer resection google scholar","probabilities":0.9799733,"Title":"Predictors Of Long Term Outcomes After Pancreatic Cancer Resection","Abstract":"Abstract\nAims: There is an increasing number of complex pancreatic cancer resections. This study aimed to assess the long term outcomes and to identify factors that predict mortality. \nMethods: A prospective database of consecutive patients who underwent pancreatic cancer resection (2008-2014) was analysed. Patient and procedural characteristics were collected including age, co-morbidities, tumour histopathology, lymph node involvement and Superior Mesenteric/Portal vein (SMV/PV) resection. Logistic regression analysis was used to correlate the above factors with all-cause mortality. Long term mortality rates were further studied based on tumour resection margins.\nResults: A total of 80 patients (42 males, median age 68 [42-82]) were included in the study and followed up for a median time of 6 (4-11yrs). Resected malignancies included pancreatic adenocarcinoma (n=43), ampullary adenocarcinoma (n=27), and cholangiocarcinoma (n=10). \nThe 1, 3 and 5yr mortality were 5%, 40%, and 56%, respectively for pancreatic adenocarcinoma, 11%, 22%, and 27%, respectively for ampullary adenocarcinoma, and 10%, 60%, and 80%, respectively for cholangiocarcinoma. Over-all 5yr survival rate was higher in the ampullary cancer group (P=0.01).\nSMV/PV resection (OR 1.28 (0.2-8.4), P=0.02), lymph node involvement (OR 0.33 (0.98-1.09), P<0.04), and cancer recurrence (OR 0.1 (0.03-0.34), P<0.0001), were the only independent factors predictive of long term mortality.\nDisease free tumour margins showed higher survival rate (P=0.005), this was more evident in ampullary adenocarcinomas (P=0.007).\nConclusions: Ampullary adenocarcinomas are associated with a better long term survival. SMV/PV resection, lymph node involvement, and cancer recurrence are the strongest predictors of long-term mortality after pancreatic cancer resection.","Source":"Google Scholar","category":"HUMAN","training_data":"Predictors Of Long Term Outcomes After Pancreatic Cancer Resection Abstract\nAims: There is an increasing number of complex pancreatic cancer resections. This study aimed to assess the long term outcomes and to identify factors that predict mortality. \nMethods: A prospective database of consecutive patients who underwent pancreatic cancer resection (2008-2014) was analysed. Patient and procedural characteristics were collected including age, co-morbidities, tumour histopathology, lymph node involvement and Superior Mesenteric/Portal vein (SMV/PV) resection. Logistic regression analysis was used to correlate the above factors with all-cause mortality. Long term mortality rates were further studied based on tumour resection margins.\nResults: A total of 80 patients (42 males, median age 68 [42-82]) were included in the study and followed up for a median time of 6 (4-11yrs). Resected malignancies included pancreatic adenocarcinoma (n=43), ampullary adenocarcinoma (n=27), and cholangiocarcinoma (n=10). \nThe 1, 3 and 5yr mortality were 5%, 40%, and 56%, respectively for pancreatic adenocarcinoma, 11%, 22%, and 27%, respectively for ampullary adenocarcinoma, and 10%, 60%, and 80%, respectively for cholangiocarcinoma. Over-all 5yr survival rate was higher in the ampullary cancer group (P=0.01).\nSMV/PV resection (OR 1.28 (0.2-8.4), P=0.02), lymph node involvement (OR 0.33 (0.98-1.09), P<0.04), and cancer recurrence (OR 0.1 (0.03-0.34), P<0.0001), were the only independent factors predictive of long term mortality.\nDisease free tumour margins showed higher survival rate (P=0.005), this was more evident in ampullary adenocarcinomas (P=0.007).\nConclusions: Ampullary adenocarcinomas are associated with a better long term survival. SMV/PV resection, lymph node involvement, and cancer recurrence are the strongest predictors of long-term mortality after pancreatic cancer resection. \n Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"impact biliary stent related events patients diagnosed advanced pancreatobiliary tumours receiving palliative chemotherapy aim determine impact morbidity mortality biliary stent related events sre cholangitis stent obstruction chemotherapy treated pancreatico biliary patients methods consecutive patients advanced pancreatobiliary cancer biliary stent situ prior starting palliative chemotherapy identified retrospectively local electronic case note records jan 13 jan 15 primary end point sre rate time sre defined time first stenting chemotherapy date sre progression free survival overall survival measured time starting chemotherapy kaplan meier cox fine gray regression univariate multivariable analyses employed appropriate analysis time sre death considered competing event results ninety six 693 screened patients eligible 89 metal stent remainder plastic median time follow 9 6 mo range 2 2 26 4 forty one patients 43 developed sre follow cholangitis 39 stent obstruction 29 32 significant differences baseline characteristics sre group sre groups recorded sre consequences none 37 chemotherapy delay 24 discontinuation 17 death 22 median time sre 4 4 mo 95 ci 3 6 5 5 patients severe comorbidities p 0 001 patients 2 baseline stents biliary procedures hr 2 3 95 ci 1 2 4 44 p 0 010 shorter time sre multivariable analysis stage independent prognostic factor overall survival p 0 029 multivariable analysis adjusted primary tumour site performance status development sre sre group vs sre group conclusion sres common impact patient morbidity results highlight need prospective studies exploring role prophylactic strategies prevent delay sres pubmed","probabilities":0.9799733,"Title":"Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy","Abstract":"AIM: To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). CONCLUSION: SREs are common and impact on patient's morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs.","Source":"PubMed","category":"HUMAN","training_data":"Impact of biliary stent-related events in patients diagnosed with advanced pancreatobiliary tumours receiving palliative chemotherapy AIM: To determine the impact (morbidity/mortality) of biliary stent-related events (SRE) (cholangitis or stent obstruction) in chemotherapy-treated pancreatico-biliary patients. METHODS: All consecutive patients with advanced pancreatobiliary cancer and a biliary stent in-situ prior to starting palliative chemotherapy were identified retrospectively from local electronic case-note records (Jan 13 to Jan 15). The primary end-point was SRE rate and the time-to-SRE (defined as time from first stenting before chemotherapy to date of SRE). Progression-free survival and overall survival were measured from the time of starting chemotherapy. Kaplan-Meier, Cox and Fine-Gray regression (univariate and multivariable) analyses were employed, as appropriate. For the analysis of time-to-SRE, death was considered as a competing event. RESULTS: Ninety-six out of 693 screened patients were eligible; 89% had a metal stent (the remainder were plastic). The median time of follow-up was 9.6 mo (range 2.2 to 26.4). Forty-one patients (43%) developed a SRE during follow-up [cholangitis (39%), stent obstruction (29%), both (32%)]. There were no significant differences in baseline characteristics between the SRE group and no-SRE groups. Recorded SRE-consequences were: none (37%), chemotherapy delay (24%), discontinuation (17%) and death (22%). The median time-to-SRE was 4.4 mo (95%CI: 3.6-5.5). Patients with severe comorbidities (P < 0.001) and patients with ≥ 2 baseline stents/biliary procedures [HR = 2.3 (95%CI: 1.2-4.44), P = 0.010] had a shorter time-to-SRE on multivariable analysis. Stage was an independent prognostic factor for overall survival (P = 0.029) in the multivariable analysis adjusted for primary tumour site, performance status and development of SRE (SRE group vs no-SRE group). CONCLUSION: SREs are common and impact on patient's morbidity. Our results highlight the need for prospective studies exploring the role of prophylactic strategies to prevent/delay SREs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value positive surgical margins resection cholangiocarcinoma experience high volume hospital center specializing hepatopancreatobiliary surgery valor pronostico del margen quirurgico positivo tras la reseccion de un colangiocarcinoma experiencia en un centro de alto volumen en cirugia hepatopancreatobiliar introduction aims cholangiocarcinoma accounts 3 gastrointestinal tumors second frequent hepatic neoplasia hepatocellular carcinoma primary aim evaluate median disease free period survival patients cholangiocarcinoma diagnosis comparison r0 r1 resection margins materials methods retrospective analysis conducted 36 patients underwent type surgical resection due cholangiocarcinoma diagnosis within time frame 2000 2017 center specializing hepatopancreatobiliary surgery population preoperative oncologic variables included ibm statistical package social sciences mac version 16 0 software ibm spss inc chicago il usa employed results thirty one patients underwent hepatectomy whipple procedure bypass surgery depending tumor location statistical significance survival patients positive margins negative margins evaluated mann whitney u test p 05 reference value statistically significant difference found overall morbidity rate 58 06 n 18 mortality rate 12 9 n 4 conclusions statistically significant difference relation incidence disease recurrence general survival resulted comparison microscopically positive surgical margins r1 negative surgical margins r0 also correlation preoperative ca 19 9 levels disease prognosis google scholar","probabilities":0.9799733,"Title":"Prognostic Value Of Positive Surgical Margins After Resection Of Cholangiocarcinoma Experience At A High-Volume Hospital Center Specializing In Hepatopancreatobiliary Surgery Valor Pronostico Del Margen Quirurgico Positivo Tras La Reseccion De Un Colangiocarcinoma Experiencia En Un Centro De Alto Volumen En Cirugia Hepatopancreatobiliar","Abstract":"Introduction and aims\nCholangiocarcinoma accounts for 3% of gastrointestinal tumors and is the second most frequent hepatic neoplasia after hepatocellular carcinoma. The primary aim was to evaluate the median disease-free period and survival in patients with cholangiocarcinoma diagnosis through the comparison of R0 and R1 resection margins.\nMaterials and methods\nA retrospective analysis was conducted on 36 patients that underwent some type of surgical resection due to cholangiocarcinoma diagnosis, within the time frame of 2000-2017, at a center specializing in hepatopancreatobiliary surgery. Population, preoperative, and oncologic variables were included. The IBM Statistical Package for the Social Sciences for Mac, version 16.0, software (IBM SPSS Inc., Chicago, IL, USA) was employed.\nResults\nThirty-one patients underwent hepatectomy, the Whipple procedure, or bypass surgery, depending on tumor location. The statistical significance of survival between patients with positive margins and those with negative margins was evaluated through the Mann-Whitney U test, with a P<.05 as the reference value. No statistically significant difference was found. The overall morbidity rate was 58.06% (n=18) and the mortality rate was 12.9% (n=4).\nConclusions\nNo statistically significant difference in relation to the incidence of disease recurrence or general survival resulted from the comparison of microscopically positive surgical margins (R1) and negative surgical margins (R0). There was also no correlation between preoperative CA 19-9 levels and disease prognosis.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Value Of Positive Surgical Margins After Resection Of Cholangiocarcinoma Experience At A High-Volume Hospital Center Specializing In Hepatopancreatobiliary Surgery Valor Pronostico Del Margen Quirurgico Positivo Tras La Reseccion De Un Colangiocarcinoma Experiencia En Un Centro De Alto Volumen En Cirugia Hepatopancreatobiliar Introduction and aims\nCholangiocarcinoma accounts for 3% of gastrointestinal tumors and is the second most frequent hepatic neoplasia after hepatocellular carcinoma. The primary aim was to evaluate the median disease-free period and survival in patients with cholangiocarcinoma diagnosis through the comparison of R0 and R1 resection margins.\nMaterials and methods\nA retrospective analysis was conducted on 36 patients that underwent some type of surgical resection due to cholangiocarcinoma diagnosis, within the time frame of 2000-2017, at a center specializing in hepatopancreatobiliary surgery. Population, preoperative, and oncologic variables were included. The IBM Statistical Package for the Social Sciences for Mac, version 16.0, software (IBM SPSS Inc., Chicago, IL, USA) was employed.\nResults\nThirty-one patients underwent hepatectomy, the Whipple procedure, or bypass surgery, depending on tumor location. The statistical significance of survival between patients with positive margins and those with negative margins was evaluated through the Mann-Whitney U test, with a P<.05 as the reference value. No statistically significant difference was found. The overall morbidity rate was 58.06% (n=18) and the mortality rate was 12.9% (n=4).\nConclusions\nNo statistically significant difference in relation to the incidence of disease recurrence or general survival resulted from the comparison of microscopically positive surgical margins (R1) and negative surgical margins (R0). There was also no correlation between preoperative CA 19-9 levels and disease prognosis. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"comparison time trends gallbladder cancer mortality 1990 2006 countries based using mortality database mortality data abstracted world health organization database available various countries used gallbladder cancer mortality icd 10 c23 c34 10 countries period 1990 2006 countries japan china hong kong republic korea asian countries united states america usa australia united kingdom uk italy spain france germany european countries usa spain france data available 1990 2005 australia italy 1990 2003 world population used age standardization age standardized rates gallbladder cancer mortality icd 10 c23 c24 10 selected countries 1990 2006 shown males fig 1 females fig 2 among males age standardized rates japan republic korea considerably higher countries studied mortality rates republic korea appeared increased late 1990s decreased japan period contrast asian countries china hong kong showed lower rates strong decreasing trend late 1990s mortality usa australia relatively low showed slight decreasing trends europe uk lowest mortality rate observation period followed spain france showed similar rates trend although italy germany showed highest europe germany decreasing trend whereas italy change google scholar","probabilities":0.9799733,"Title":"Comparison Of Time Trends In Gallbladder Cancer Mortality (1990-2006) Between Countries Based Using The Who Mortality Database","Abstract":"Mortality data, abstracted from the World Health Organization (WHO) database, are available for various countries. We used gallbladder cancer mortality (ICD-10: C23–C34) in 10 countries during the period 1990–2006. These countries were Japan, China (Hong Kong) and the Republic of Korea (Asian countries); the United States of America (USA); Australia; the United Kingdom (UK); and Italy, Spain, France and Germany (European countries). For the USA, Spain and France, data were available only for 1990–2005; and for Australia and Italy, for 1990–2003. The world population was used for age standardization. Age-standardized rates for gallbladder cancer mortality (ICD-10: C23–C24) in the 10 selected countries between 1990 and 2006 are shown for males (Fig. 1) and females (Fig. 2). Among males, age-standardized rates in Japan and the Republic of Korea were considerably higher than the other countries studied. Mortality rates in the Republic of Korea appeared to have increased from the late 1990s but decreased in Japan over the period. In contrast to the other Asian countries, China (Hong Kong) showed lower rates with a strong decreasing trend until the late 1990s. Mortality in the USA and Australia was relatively low and showed slight decreasing trends. In Europe, the UK had the lowest mortality rate during the observation period, followed by Spain and France which showed similar rates and trend. Although both Italy and Germany showed the highest in Europe, Germany had a decreasing trend, whereas Italy did not change.","Source":"Google Scholar","category":"HUMAN","training_data":"Comparison Of Time Trends In Gallbladder Cancer Mortality (1990-2006) Between Countries Based Using The Who Mortality Database Mortality data, abstracted from the World Health Organization (WHO) database, are available for various countries. We used gallbladder cancer mortality (ICD-10: C23–C34) in 10 countries during the period 1990–2006. These countries were Japan, China (Hong Kong) and the Republic of Korea (Asian countries); the United States of America (USA); Australia; the United Kingdom (UK); and Italy, Spain, France and Germany (European countries). For the USA, Spain and France, data were available only for 1990–2005; and for Australia and Italy, for 1990–2003. The world population was used for age standardization. Age-standardized rates for gallbladder cancer mortality (ICD-10: C23–C24) in the 10 selected countries between 1990 and 2006 are shown for males (Fig. 1) and females (Fig. 2). Among males, age-standardized rates in Japan and the Republic of Korea were considerably higher than the other countries studied. Mortality rates in the Republic of Korea appeared to have increased from the late 1990s but decreased in Japan over the period. In contrast to the other Asian countries, China (Hong Kong) showed lower rates with a strong decreasing trend until the late 1990s. Mortality in the USA and Australia was relatively low and showed slight decreasing trends. In Europe, the UK had the lowest mortality rate during the observation period, followed by Spain and France which showed similar rates and trend. Although both Italy and Germany showed the highest in Europe, Germany had a decreasing trend, whereas Italy did not change. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cutaneous metastasis cholangiocarcinoma aim investigate clinical characteristics prognostic factors cutaneous metastasis cholangiocarcinoma retrospective analysis published cases methods extensive search conducted english literature within pubmed database using following keywords cutaneous metastasis skin metastasis cholangiocarcinoma bile duct data 30 patients 21 articles 1978 2014 analyzed patient data retrieved articles included following age gender time cutaneous metastasis occurred number cutaneous metastases throughout life sites initial cutaneous metastasis anatomic site pathology differentiation cholangiocarcinoma immunohistochemical results cutaneous metastasis assessment overall survival cutaneous metastasis oscm primary endpoint results median age diagnosis cutaneous metastasis cholangiocarcinoma 60 0 years range 35 77 metastasis showed predilection towards males male female ratio 3 29 8 cases 27 6 skin metastasis first sign cholangiocarcinoma additionally 18 cases 60 0 manifested single cutaneous metastasis 12 cases 40 0 demonstrated multiple skin metastases 50 0 patients metastasis occurred drainage region 50 0 patients distant cutaneous metastases scalp frequently involved region distant skin metastasis occurring 36 7 patients median oscm cholangiocarcinoma 4 0 mo patient age cutaneous metastatic sites showed significant relation oscm male gender single metastasis skin associated poorer oscm hazard ratio 0 168 p 0 005 hazard ratio 0 296 p 0 011 respectively conclusion prognosis cutaneous metastasis cholangiocarcinoma dismal male gender single skin metastasis associated poorer oscm pubmed","probabilities":0.9799733,"Title":"Cutaneous metastasis of cholangiocarcinoma","Abstract":"AIM: To investigate the clinical characteristics and prognostic factors of cutaneous metastasis of cholangiocarcinoma by a retrospective analysis of published cases. METHODS: An extensive search was conducted in the English literature within the PubMed database using the following keywords: cutaneous metastasis or skin metastasis and cholangiocarcinoma or bile duct. The data of 30 patients from 21 articles from 1978 to 2014 were analyzed. Patient data retrieved from the articles included the following: age, gender, time cutaneous metastasis occurred, number of cutaneous metastases throughout life, sites of initial cutaneous metastasis, anatomic site, pathology and differentiation of cholangiocarcinoma, and immunohistochemical results of the cutaneous metastasis. The assessment of overall survival after cutaneous metastasis (OSCM) was the primary endpoint. RESULTS: The median age at diagnosis of cutaneous metastasis of cholangiocarcinoma was 60.0 years (range: 35-77). This metastasis showed a predilection towards males, with a male to female ratio of 3.29. In 8 cases (27.6%), skin metastasis was the first sign of cholangiocarcinoma. Additionally, 18 cases (60.0%) manifested single cutaneous metastasis, while 12 cases (40.0%) demonstrated multiple skin metastases. In 50.0% of patients, the metastasis occurred in the drainage region, while 50.0% of patients had distant cutaneous metastases. The scalp was the most frequently involved region of distant skin metastasis, occurring in 36.7% of patients. The median OSCM of cholangiocarcinoma was 4.0 mo. Patient age and cutaneous metastatic sites showed no significant relation with OSCM, while male gender and single metastasis of the skin were associated with a poorer OSCM (hazard ratio: 0.168; P = 0.005, and hazard ratio: 0.296; P = 0.011, respectively). CONCLUSION: The prognosis of cutaneous metastasis of cholangiocarcinoma is dismal. Both male gender and single skin metastasis are associated with a poorer OSCM.","Source":"PubMed","category":"HUMAN","training_data":"Cutaneous metastasis of cholangiocarcinoma AIM: To investigate the clinical characteristics and prognostic factors of cutaneous metastasis of cholangiocarcinoma by a retrospective analysis of published cases. METHODS: An extensive search was conducted in the English literature within the PubMed database using the following keywords: cutaneous metastasis or skin metastasis and cholangiocarcinoma or bile duct. The data of 30 patients from 21 articles from 1978 to 2014 were analyzed. Patient data retrieved from the articles included the following: age, gender, time cutaneous metastasis occurred, number of cutaneous metastases throughout life, sites of initial cutaneous metastasis, anatomic site, pathology and differentiation of cholangiocarcinoma, and immunohistochemical results of the cutaneous metastasis. The assessment of overall survival after cutaneous metastasis (OSCM) was the primary endpoint. RESULTS: The median age at diagnosis of cutaneous metastasis of cholangiocarcinoma was 60.0 years (range: 35-77). This metastasis showed a predilection towards males, with a male to female ratio of 3.29. In 8 cases (27.6%), skin metastasis was the first sign of cholangiocarcinoma. Additionally, 18 cases (60.0%) manifested single cutaneous metastasis, while 12 cases (40.0%) demonstrated multiple skin metastases. In 50.0% of patients, the metastasis occurred in the drainage region, while 50.0% of patients had distant cutaneous metastases. The scalp was the most frequently involved region of distant skin metastasis, occurring in 36.7% of patients. The median OSCM of cholangiocarcinoma was 4.0 mo. Patient age and cutaneous metastatic sites showed no significant relation with OSCM, while male gender and single metastasis of the skin were associated with a poorer OSCM (hazard ratio: 0.168; P = 0.005, and hazard ratio: 0.296; P = 0.011, respectively). CONCLUSION: The prognosis of cutaneous metastasis of cholangiocarcinoma is dismal. Both male gender and single skin metastasis are associated with a poorer OSCM. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value neutrophil lymphocyte ratio nlr determining survival patients hilar cholangiocarcinoma hcca background hilar cholangiocarcinoma hcca arises bifurcation common hepatic duct inflammation proposed emerging hallmark cancer patholologic observations demonstrating infiltration cancerous tissue tumour microenvironment immune cells neutrophil lymphocyte ratio nlr proposed predictor survival outcome context surgical oncology aimed investigate relationship exists nlr overall survival os hcca patients resected non resected hcca patients google scholar","probabilities":0.7966102,"Title":"The Prognostic Value Of The Neutrophil To Lymphocyte Ratio (Nlr) In Determining Survival In Patients With Hilar Cholangiocarcinoma (Hcca)","Abstract":"Background: Hilar cholangiocarcinoma (HCCA) arises from the bifurcation of the common hepatic duct. Inflammation has been proposed as an emerging hallmark of cancer, with patholologic observations demonstrating infiltration of cancerous tissue and the tumour microenvironment with immune cells. Neutrophil to lymphocyte ratio (NLR) has been proposed as a predictor of survival outcome in context of surgical oncology. We aimed to investigate what relationship, if any, exists between NLR and overall survival (OS) in HCCA patients who have been resected and non-resected HCCA patients.","Source":"Google Scholar","category":"HUMAN","training_data":"The Prognostic Value Of The Neutrophil To Lymphocyte Ratio (Nlr) In Determining Survival In Patients With Hilar Cholangiocarcinoma (Hcca) Background: Hilar cholangiocarcinoma (HCCA) arises from the bifurcation of the common hepatic duct. Inflammation has been proposed as an emerging hallmark of cancer, with patholologic observations demonstrating infiltration of cancerous tissue and the tumour microenvironment with immune cells. Neutrophil to lymphocyte ratio (NLR) has been proposed as a predictor of survival outcome in context of surgical oncology. We aimed to investigate what relationship, if any, exists between NLR and overall survival (OS) in HCCA patients who have been resected and non-resected HCCA patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"transarterial therapies unresectable cholangiocarcinoma meta analysis purpose locoregional therapies proven effective treating many liver malignancies however data regarding cholangiocarcinoma cca less robust purpose study perform meta analysis evaluate effectiveness transarterial therapies treatment cca materials methods literature searches pubmed embase performed july 2011 original search broad included article mentioned locoregional therapy kind bile duct malignancy medical librarian also performed parallel searches primary manuscripts abstracts involving patients unresectable cholangiocarcinoma presented data survival imaging response toxicity profile following locoregional therapy included final analysis studies evaluating multiple tumor types included data cca patients presented separately results original search resulted 316 citations 14 articles reporting 391 patients met inclusion criteria data 14 studies reported table 1 differences reporting survival chemotherapeutic embolization agent used made direct comparisons difficult included studies patients similar child pugh scores 0 class c ecog status rates metastatic disease calculated weighted cumulative median survival date diagnosis 15 6 1 1 months nearly half 49 8 patients stable disease recist criteria total 579 procedures done averaging 2 99 treatments per patient two 14 studies use embolization agent severe toxicity rate nci v 3 6 7 google scholar","probabilities":0.9799733,"Title":"Transarterial Therapies For Unresectable Cholangiocarcinoma: A Meta-Analysis","Abstract":"Purpose\nLocoregional therapies have proven effective in treating many liver malignancies. However, data regarding cholangiocarcinoma (CCA) are less robust. The purpose of this study was to perform a meta-analysis to evaluate the effectiveness of transarterial therapies in the treatment of CCA.\nMaterials and Methods\nLiterature searches in both PubMed and EMBASE were performed in July of 2011. The original search was broad, and included any article that mentioned a locoregional therapy and any kind of bile duct malignancy. A medical librarian also performed parallel searches. All primary manuscripts and abstracts involving patients with unresectable cholangiocarcinoma, and that presented data on survival, imaging response, and toxicity profile following locoregional therapy were included in our final analysis. Studies evaluating multiple tumor types were included only if data for CCA patients were presented separately.\nResults\nThe original search resulted in 316 citations; of these, 14 articles reporting on 391 patients met the inclusion criteria. Data from these 14 studies are reported in Table 1. Differences in reporting survival, and in chemotherapeutic and embolization agent used, made direct comparisons difficult. In the included studies, patients had similar Child Pugh scores (0% Class C), ECOG status, and rates of metastatic disease. The calculated weighted cumulative median survival, from date of diagnosis, was 15.6 ±1.1 months. Nearly half (49.8%) of all patients had stable disease by RECIST criteria. There were a total of 579 procedures done, averaging 2.99 treatments per patient. Only two of 14 studies did not use an embolization agent. The severe toxicity rate (NCI v.3) was 6.7%.","Source":"Google Scholar","category":"HUMAN","training_data":"Transarterial Therapies For Unresectable Cholangiocarcinoma: A Meta-Analysis Purpose\nLocoregional therapies have proven effective in treating many liver malignancies. However, data regarding cholangiocarcinoma (CCA) are less robust. The purpose of this study was to perform a meta-analysis to evaluate the effectiveness of transarterial therapies in the treatment of CCA.\nMaterials and Methods\nLiterature searches in both PubMed and EMBASE were performed in July of 2011. The original search was broad, and included any article that mentioned a locoregional therapy and any kind of bile duct malignancy. A medical librarian also performed parallel searches. All primary manuscripts and abstracts involving patients with unresectable cholangiocarcinoma, and that presented data on survival, imaging response, and toxicity profile following locoregional therapy were included in our final analysis. Studies evaluating multiple tumor types were included only if data for CCA patients were presented separately.\nResults\nThe original search resulted in 316 citations; of these, 14 articles reporting on 391 patients met the inclusion criteria. Data from these 14 studies are reported in Table 1. Differences in reporting survival, and in chemotherapeutic and embolization agent used, made direct comparisons difficult. In the included studies, patients had similar Child Pugh scores (0% Class C), ECOG status, and rates of metastatic disease. The calculated weighted cumulative median survival, from date of diagnosis, was 15.6 ±1.1 months. Nearly half (49.8%) of all patients had stable disease by RECIST criteria. There were a total of 579 procedures done, averaging 2.99 treatments per patient. Only two of 14 studies did not use an embolization agent. The severe toxicity rate (NCI v.3) was 6.7%. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"response treatment selective internal radiation therapy y90 sirt patients unresectable multifocal intrahepatic cholangiocarcinoma results preliminary study abstract available google scholar","probabilities":0.9799733,"Title":"Response To Treatment With Selective Internal Radiation Therapy Y90 (Sirt) In Patients With Unresectable Multifocal Intrahepatic Cholangiocarcinoma: Results Of A Preliminary Study","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Response To Treatment With Selective Internal Radiation Therapy Y90 (Sirt) In Patients With Unresectable Multifocal Intrahepatic Cholangiocarcinoma: Results Of A Preliminary Study Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"maa based dosimetric study patients intrahepatic cholangiocarcinoma treated combination chemotherapy 90 y loaded glass microsphere selective internal radiation therapy purpose selective internal radiation therapy sirt appears interesting treatment possibility locally advanced intrahepatic cholangiocarcinoma icc yet appropriate dosimetry never evaluated context methods retrospectively studied data 40 patients treated institution 90 y loaded glass microsphere sirt combined chemotherapy inoperable icc first line treatment macroaggregated albumin maa based single photon emission computed tomography spect computed tomography ct quantitative analysis used calculate tumor dose td healthy injected liver dose hild injected liver dose ild response evaluated 3 months using european association study liver criteria factors associated response toxicity analyzed using univariate analysis results assessed total 35 patients five excluded receiving 55 injections mean td 322 165gy mean hild 74 24gy mean ild 128 28gy two lesions responded minimal td responding lesions 158gy six grade 3 4 permanent liver toxicities observed mean hild associated liver toxicity 73 2 25 8gy patients liver toxicity 77 8 16 9gy patients without ns underlying child pugh status p 0 0014 underlying cirrhosis p 0 0021 associated liver toxicity median progression free survival 12 7 months median overall survival os 28 6 months median os 52 7 months patients child pugh a5 status conclusions combined chemotherapy sirt highly effective td 158gy tolerance good except patients cirrhosis child pugh status a6 exhibited liver toxicity prospective studies warranted confirm pubmed","probabilities":0.9799733,"Title":"A MAA-based dosimetric study in patients with intrahepatic cholangiocarcinoma treated with a combination of chemotherapy and (90)Y-loaded glass microsphere selective internal radiation therapy","Abstract":"PURPOSE: Selective internal radiation therapy (SIRT) appears to be an interesting treatment possibility for locally-advanced intrahepatic cholangiocarcinoma (ICC), yet the appropriate dosimetry has never been evaluated in this context. METHODS: We retrospectively studied data from 40 patients treated at our institution with (90)Y-loaded glass microsphere SIRT combined with chemotherapy for inoperable ICC as first-line treatment. Macroaggregated albumin (MAA)-based single-photon emission computed tomography (SPECT)/computed tomography (CT) quantitative analysis was used to calculate the tumor dose (TD), healthy-injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3 months using the European Association for the Study of the Liver criteria. Factors associated with response and toxicity were analyzed using univariate analysis. RESULTS: We assessed a total of 35 patients (five excluded) receiving 55 injections. Mean TD was 322 ± 165Gy and mean HILD was 74 ± 24Gy for a mean ILD of 128 ± 28Gy. All but two lesions responded, with a minimal TD for responding lesions of 158Gy. Six Grade 3-4 permanent liver toxicities were observed. Mean HILD was not associated with liver toxicity (73.2 ± 25.8Gy for patients with liver toxicity and 77.8 ± 16.9Gy for patients without, ns). Only underlying Child-Pugh status (p = 0.0014) and underlying cirrhosis (p = 0.0021) were associated with liver toxicity. Median progression-free survival was 12.7 months and median overall survival (OS) was 28.6 months. Median OS was 52.7 months for patients with Child-Pugh A5 status. CONCLUSIONS: When combined with chemotherapy, SIRT is highly effective, with a TD > 158Gy. Tolerance was good except for the few patients with cirrhosis or Child-Pugh status ≥A6, who exhibited some liver toxicity. Prospective studies are warranted to confirm.","Source":"PubMed","category":"HUMAN","training_data":"A MAA-based dosimetric study in patients with intrahepatic cholangiocarcinoma treated with a combination of chemotherapy and (90)Y-loaded glass microsphere selective internal radiation therapy PURPOSE: Selective internal radiation therapy (SIRT) appears to be an interesting treatment possibility for locally-advanced intrahepatic cholangiocarcinoma (ICC), yet the appropriate dosimetry has never been evaluated in this context. METHODS: We retrospectively studied data from 40 patients treated at our institution with (90)Y-loaded glass microsphere SIRT combined with chemotherapy for inoperable ICC as first-line treatment. Macroaggregated albumin (MAA)-based single-photon emission computed tomography (SPECT)/computed tomography (CT) quantitative analysis was used to calculate the tumor dose (TD), healthy-injected liver dose (HILD), and injected liver dose (ILD). Response was evaluated at 3 months using the European Association for the Study of the Liver criteria. Factors associated with response and toxicity were analyzed using univariate analysis. RESULTS: We assessed a total of 35 patients (five excluded) receiving 55 injections. Mean TD was 322 ± 165Gy and mean HILD was 74 ± 24Gy for a mean ILD of 128 ± 28Gy. All but two lesions responded, with a minimal TD for responding lesions of 158Gy. Six Grade 3-4 permanent liver toxicities were observed. Mean HILD was not associated with liver toxicity (73.2 ± 25.8Gy for patients with liver toxicity and 77.8 ± 16.9Gy for patients without, ns). Only underlying Child-Pugh status (p = 0.0014) and underlying cirrhosis (p = 0.0021) were associated with liver toxicity. Median progression-free survival was 12.7 months and median overall survival (OS) was 28.6 months. Median OS was 52.7 months for patients with Child-Pugh A5 status. CONCLUSIONS: When combined with chemotherapy, SIRT is highly effective, with a TD > 158Gy. Tolerance was good except for the few patients with cirrhosis or Child-Pugh status ≥A6, who exhibited some liver toxicity. Prospective studies are warranted to confirm. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extended right hemihepatectomy gallbladder carcinoma involving hepatic hilum background major hemihepatectomy advanced gallbladder carcinoma remains controversial associated serious postoperative complications poor prognosis methods underwent extended right hemihepatectomy identified database patients gallbladder carcinoma surgical resection 1999 2009 clinicopathological data patients analysed retrospectively results total 126 patients underwent surgical resection 35 extended right hemihepatectomy deaths 16 patients complications mean d duration operation blood loss 564 206 min 1472 1268 ml respectively blood transfusions needed 28 patients tumour stage international union cancer sixth edition iia four iib four iii 15 iv 12 patients overall 5 year survival rate 17 per cent median survival 2 2 years three patients survived 5 years presence hepatic metastases gallbladder carcinoma originating cystic duct indicators poor prognosis conclusion extended right hemihepatectomy gallbladder cancer safe may contribute long term survival selected patients pubmed","probabilities":0.9799733,"Title":"Extended right hemihepatectomy for gallbladder carcinoma involving the hepatic hilum","Abstract":"BACKGROUND: Major hemihepatectomy for advanced gallbladder carcinoma remains controversial as it is associated with serious postoperative complications and poor prognosis. METHODS: All those who underwent extended right hemihepatectomy were identified from a database of patients with gallbladder carcinoma who had surgical resection between 1999 and 2009. The clinicopathological data for these patients were analysed retrospectively. RESULTS: A total of 126 patients underwent surgical resection, 35 of whom had extended right hemihepatectomy. There were no deaths, but 16 patients had complications. The mean(s.d.) duration of operation and blood loss were 564(206) min and 1472(1268) ml respectively. No blood transfusions were needed in 28 patients. Tumour stage (International Union Against Cancer, sixth edition) was IIA in four, IIB in four, III in 15 and IV in 12 patients. The overall 5-year survival rate was 17 per cent with a median survival of 2·2 years. Three patients survived more than 5 years. The presence of hepatic metastases and gallbladder carcinoma originating from the cystic duct were indicators of poor prognosis. CONCLUSION: Extended right hemihepatectomy for gallbladder cancer is safe and may contribute to long-term survival in selected patients.","Source":"PubMed","category":"HUMAN","training_data":"Extended right hemihepatectomy for gallbladder carcinoma involving the hepatic hilum BACKGROUND: Major hemihepatectomy for advanced gallbladder carcinoma remains controversial as it is associated with serious postoperative complications and poor prognosis. METHODS: All those who underwent extended right hemihepatectomy were identified from a database of patients with gallbladder carcinoma who had surgical resection between 1999 and 2009. The clinicopathological data for these patients were analysed retrospectively. RESULTS: A total of 126 patients underwent surgical resection, 35 of whom had extended right hemihepatectomy. There were no deaths, but 16 patients had complications. The mean(s.d.) duration of operation and blood loss were 564(206) min and 1472(1268) ml respectively. No blood transfusions were needed in 28 patients. Tumour stage (International Union Against Cancer, sixth edition) was IIA in four, IIB in four, III in 15 and IV in 12 patients. The overall 5-year survival rate was 17 per cent with a median survival of 2·2 years. Three patients survived more than 5 years. The presence of hepatic metastases and gallbladder carcinoma originating from the cystic duct were indicators of poor prognosis. CONCLUSION: Extended right hemihepatectomy for gallbladder cancer is safe and may contribute to long-term survival in selected patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term outcome distal cholangiocarcinoma pancreaticoduodenectomy followed adjuvant chemoradiotherapy 15 year experience single institution purpose study conducted evaluate long term outcome patients undergoing pancreaticoduodenectomy pd followed adjuvant chemoradiotherapy distal cholangiocarcinoma dcc high volume center identify prognostic impact clinicopathologic factors materials methods total 132 consecutive patients met inclusion criteria retrieved institutional database january 1995 september 2009 patients received adjuvant treatments median 45 days surgery median follow duration 57 months range 6 225 months patients 105 months survivors range 13 225 months results 5 year locoregional recurrence free survival lrrfs distant metastasis free survival dmfs disease free survival dfs overall survival os rates 70 7 55 7 49 4 48 1 respectively univariate analysis revealed poorly differentiated p d tumors lymph node ln metastasis significantly associated dmfs os additionally preoperative carbohydrate antigen 19 9 level significantly correlated dfs lrrfs dmfs upon multivariate analysis os p d tumors p 0 015 ln metastasis p 0 003 significant prognosticators predicted inferior os grade 3 higher late gastrointestinal toxicity occurred one patient 0 8 conclusion adjuvant chemoradiotherapy pd dcc effective tolerable strategy without significant side effects long term follow found prognosis dcc mainly influenced histologic differentiation ln metastasis patients risk factors research focus improving adjuvant strategies well treatment approaches pubmed","probabilities":0.9799733,"Title":"Long-Term Outcome of Distal Cholangiocarcinoma after Pancreaticoduodenectomy Followed by Adjuvant Chemoradiotherapy: A 15-Year Experience in a Single Institution","Abstract":"PURPOSE: This study was conducted to evaluate the long-term outcome in patients undergoing pancreaticoduodenectomy (PD) followed by adjuvant chemoradiotherapy for distal cholangiocarcinoma (DCC) in a high-volume center and to identify the prognostic impact of clinicopathologic factors. MATERIALS AND METHODS: A total of 132 consecutive patients who met the inclusion criteria were retrieved from the institutional database from January 1995 to September 2009. All patients received adjuvant treatments at a median of 45 days after the surgery. Median follow-up duration was 57 months (range, 6 to 225 months) for all patients and 105 months for survivors (range, 13 to 225 months). RESULTS: The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 70.7%, 55.7%, 49.4%, and 48.1%, respectively. Univariate analysis revealed poorly differentiated (P/D) tumors and lymph node (LN) metastasis were significantly associated with DMFS and OS. Additionally, preoperative carbohydrate antigen 19-9 level was significantly correlated with DFS, LRRFS, and DMFS. Upon multivariate analysis for OS, P/D tumors (p=0.015) and LN metastasis (p=0.003) were significant prognosticators that predicted inferior OS. Grade 3 or higher late gastrointestinal toxicity occurred in only one patient (0.8%). CONCLUSION: Adjuvant chemoradiotherapy after PD for DCC is an effective and tolerable strategy without significant side effects. During long-term follow-up, we found that prognosis of DCC was mainly influenced by histologic differentiation and LN metastasis. For patients with these risk factors, further research should focus on improving adjuvant strategies as well as other treatment approaches.","Source":"PubMed","category":"HUMAN","training_data":"Long-Term Outcome of Distal Cholangiocarcinoma after Pancreaticoduodenectomy Followed by Adjuvant Chemoradiotherapy: A 15-Year Experience in a Single Institution PURPOSE: This study was conducted to evaluate the long-term outcome in patients undergoing pancreaticoduodenectomy (PD) followed by adjuvant chemoradiotherapy for distal cholangiocarcinoma (DCC) in a high-volume center and to identify the prognostic impact of clinicopathologic factors. MATERIALS AND METHODS: A total of 132 consecutive patients who met the inclusion criteria were retrieved from the institutional database from January 1995 to September 2009. All patients received adjuvant treatments at a median of 45 days after the surgery. Median follow-up duration was 57 months (range, 6 to 225 months) for all patients and 105 months for survivors (range, 13 to 225 months). RESULTS: The 5-year locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 70.7%, 55.7%, 49.4%, and 48.1%, respectively. Univariate analysis revealed poorly differentiated (P/D) tumors and lymph node (LN) metastasis were significantly associated with DMFS and OS. Additionally, preoperative carbohydrate antigen 19-9 level was significantly correlated with DFS, LRRFS, and DMFS. Upon multivariate analysis for OS, P/D tumors (p=0.015) and LN metastasis (p=0.003) were significant prognosticators that predicted inferior OS. Grade 3 or higher late gastrointestinal toxicity occurred in only one patient (0.8%). CONCLUSION: Adjuvant chemoradiotherapy after PD for DCC is an effective and tolerable strategy without significant side effects. During long-term follow-up, we found that prognosis of DCC was mainly influenced by histologic differentiation and LN metastasis. For patients with these risk factors, further research should focus on improving adjuvant strategies as well as other treatment approaches. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression procaspase 3 activated caspase 3 relevance hormone responsive gallbladder carcinoma chemotherapy background aims higher incidence gallbladder cancer gbc females accredited involvement hormones clinical implications sex hormone receptors gbc well established cysteine proteases caspase 3 9 etc known play central role apoptotic pathway downstream enzyme caspase 3 often activated apoptotic pathway aim work examine status apoptosis directly correlated level active caspase 3 hormone responsive gbc methods used 10 androgen receptor ar positive 14 estrogen receptor er positive 12 neu positive eight triple positive 10 triple negative malignant gbc human tissue samples isolated total cellular protein tumor tissues carried western blotting using antipro caspase 3 anti activated caspase 3 antibodies results er neu positive gbc exhibited high caspase 3 activity low procaspase 3 activity whereas ar positive gbc showed significant level apoptosis also evaluated apoptosis status triple positive gbc triple negative gbc found significant apoptosis triple positive gbc conclusions results indicate er neu positive gbcs active apoptosis whereas ar positive gbc highly resistant apoptosis stn","probabilities":1.0,"Title":"Expression Of Procaspase 3 And Activated Caspase 3 And Its Relevance In Hormone-Responsive Gallbladder Carcinoma Chemotherapy","Abstract":"Background/aims: The higher incidence of gallbladder cancer (GBC) in females has been accredited to the involvement of hormones. The clinical implications of sex hormone receptors in GBC are well established. Cysteine proteases (such as caspase-3-9, etc.) are known to play a central role in the apoptotic pathway. Of these, the downstream enzyme caspase-3 is often activated in the apoptotic pathway. The aim of this work was to examine the status of apoptosis (which directly correlated with the level of active caspase-3) in hormone-responsive GBC. \r\n\r\n Methods: We used 10 androgen receptor (AR)-positive, 14 estrogen receptor (ER)-positive, 12 HER/neu-positive, eight triple positive, and 10 triple negative malignant GBC human tissue samples. We isolated the total cellular protein from tumor tissues and carried out Western blotting using antipro-caspase-3 and anti-activated caspase-3 antibodies. \r\n\r\n Results: ER and HER/neu-positive GBC exhibited high caspase-3 activity and low procaspase-3 activity, whereas AR-positive GBC showed no significant level of apoptosis. We also evaluated the apoptosis status of triple positive GBC and triple negative GBC, and found significant apoptosis in triple positive GBC. \r\n\r\n Conclusions: The results indicate that ER and HER/neu-positive GBCs had active apoptosis, whereas AR-positive GBC was highly resistant to apoptosis.","Source":"STN","category":"ANIMAL","training_data":"Expression Of Procaspase 3 And Activated Caspase 3 And Its Relevance In Hormone-Responsive Gallbladder Carcinoma Chemotherapy Background/aims: The higher incidence of gallbladder cancer (GBC) in females has been accredited to the involvement of hormones. The clinical implications of sex hormone receptors in GBC are well established. Cysteine proteases (such as caspase-3-9, etc.) are known to play a central role in the apoptotic pathway. Of these, the downstream enzyme caspase-3 is often activated in the apoptotic pathway. The aim of this work was to examine the status of apoptosis (which directly correlated with the level of active caspase-3) in hormone-responsive GBC. \r\n\r\n Methods: We used 10 androgen receptor (AR)-positive, 14 estrogen receptor (ER)-positive, 12 HER/neu-positive, eight triple positive, and 10 triple negative malignant GBC human tissue samples. We isolated the total cellular protein from tumor tissues and carried out Western blotting using antipro-caspase-3 and anti-activated caspase-3 antibodies. \r\n\r\n Results: ER and HER/neu-positive GBC exhibited high caspase-3 activity and low procaspase-3 activity, whereas AR-positive GBC showed no significant level of apoptosis. We also evaluated the apoptosis status of triple positive GBC and triple negative GBC, and found significant apoptosis in triple positive GBC. \r\n\r\n Conclusions: The results indicate that ER and HER/neu-positive GBCs had active apoptosis, whereas AR-positive GBC was highly resistant to apoptosis. STN","prediction_labels":"ANIMAL"},{"cleaned":"adjuvant therapy gallbladder cancer analysis national cancer data base background role adjuvant therapy patients resected gallbladder cancer gbc unclear methods american college surgeons national cancer data base used identify patients resected gbc pathologic stage 1 3 1998 2006 n 6690 compared three groups surgery 78 6 surgery plus adjuvant chemotherapy ac 6 2 surgery plus adjuvant chemotherapy radiation therapy acr 15 1 univariate cox regression analyses used determine factors influencing overall survival use adjuvant therapy results acr associated improved survival patients hr 0 77 95 ci 0 66 0 90 especially node positive patients hr 0 64 95 ci 0 53 0 78 ac associated changes survival patients less likely lymph nodes examined comorbidities lower income treated community cancer centers p 0 05 among patients unknown lymph node status t2 t3 disease saw improved survival acr t2 hr 0 79 95 ci 0 63 0 99 t3 hr 0 43 95 ci 0 30 0 62 ac affect survival conclusion acr associated improved survival patients node positive gbc well t2 t3 gbc unknown lymph node status pubmed","probabilities":0.9799733,"Title":"Adjuvant Therapy for Gallbladder Cancer: an Analysis of the National Cancer Data Base","Abstract":"BACKGROUND: The role of adjuvant therapy in patients with resected gallbladder cancer (GBC) is unclear. METHODS: The American College of Surgeons National Cancer Data Base was used to identify patients with resected GBC (pathologic stage 1-3) from 1998 to 2006 (n = 6690). We compared three groups: surgery only (S, 78.6 %), surgery plus adjuvant chemotherapy (AC, 6.2 %), and surgery plus adjuvant chemotherapy and radiation therapy (ACR, 15.1 %). Univariate and Cox regression analyses were used to determine factors influencing overall survival and the use of adjuvant therapy. RESULTS: ACR was associated with improved survival for all patients (HR 0.77, 95 % CI 0.66-0.90), especially node-positive patients (HR 0.64, 95 % CI 0.53-0.78); AC was not associated with changes in survival. Patients were less likely to have their lymph nodes examined if they had any comorbidities, lower income, or were treated at community cancer centers (all p < 0.05). Among patients with unknown lymph node status, those with T2 or T3 disease saw improved survival with ACR (T2: HR 0.79, 95 % CI 0.63-0.99; T3: HR 0.43, 95 % CI 0.30-0.62), while AC did not affect survival. CONCLUSION: ACR is associated with improved survival for patients with node-positive GBC, as well as those with T2 or T3 GBC with unknown lymph node status.","Source":"PubMed","category":"HUMAN","training_data":"Adjuvant Therapy for Gallbladder Cancer: an Analysis of the National Cancer Data Base BACKGROUND: The role of adjuvant therapy in patients with resected gallbladder cancer (GBC) is unclear. METHODS: The American College of Surgeons National Cancer Data Base was used to identify patients with resected GBC (pathologic stage 1-3) from 1998 to 2006 (n = 6690). We compared three groups: surgery only (S, 78.6 %), surgery plus adjuvant chemotherapy (AC, 6.2 %), and surgery plus adjuvant chemotherapy and radiation therapy (ACR, 15.1 %). Univariate and Cox regression analyses were used to determine factors influencing overall survival and the use of adjuvant therapy. RESULTS: ACR was associated with improved survival for all patients (HR 0.77, 95 % CI 0.66-0.90), especially node-positive patients (HR 0.64, 95 % CI 0.53-0.78); AC was not associated with changes in survival. Patients were less likely to have their lymph nodes examined if they had any comorbidities, lower income, or were treated at community cancer centers (all p < 0.05). Among patients with unknown lymph node status, those with T2 or T3 disease saw improved survival with ACR (T2: HR 0.79, 95 % CI 0.63-0.99; T3: HR 0.43, 95 % CI 0.30-0.62), while AC did not affect survival. CONCLUSION: ACR is associated with improved survival for patients with node-positive GBC, as well as those with T2 or T3 GBC with unknown lymph node status. PubMed","prediction_labels":"HUMAN"},{"cleaned":"association preoperative serum interleukin 6 levels postoperative prognosis patients t2 gallbladder cancer background interleukin 6 il 6 closely associated tumor progression whether predict postoperative prognosis patients t2 gallbladder cancer gbc remains controversial methods retrospectively collected medical records 125 patients t2 gbc analyzed association preoperative serum il 6 levels postoperative survival multivariate cox analyses kaplan meier curves exploratory subgroups results predictive effects serum il 6 levels overall survival similar across evaluated subgroups except different tumor location subgroups independent odds ratio serum il 6 levels 2 57 95 ci 1 73 3 82 hepatic side subgroup 1 15 95 ci 0 68 1 93 peritoneal side subgroup p 0 014 interaction categorized serum il 6 levels median value 4 2 pg ml 5 year survival rate patients high serum il 6 levels significantly higher hepatic side subgroup 58 5 vs 14 8 p 0 001 difference found peritoneal side subgroup 62 2 vs 67 6 p 0 722 conclusions preoperative serum il 6 significantly associated prognostic implications patients hepatic side t2 gbc peritoneal side tumors pubmed","probabilities":0.9799733,"Title":"The association between preoperative serum interleukin-6 levels and postoperative prognosis in patients with T2 gallbladder cancer","Abstract":"BACKGROUND: Interleukin-6 (IL-6) is closely associated with tumor progression. Whether it can predict postoperative prognosis of patients with T2 gallbladder cancer (GBC) remains controversial. METHODS: We retrospectively collected the medical records of 125 patients with T2 GBC. Then, we analyzed the association between preoperative serum IL-6 levels and postoperative survival by multivariate Cox analyses and Kaplan-Meier curves in exploratory subgroups. RESULTS: Predictive effects of serum IL-6 levels on overall survival were similar across most of the evaluated subgroups, except in different tumor location subgroups. The independent odds ratio (OR) of serum IL-6 levels was 2.57 (95%CI 1.73-3.82) in the hepatic side subgroup, while it was 1.15 (95%CI 0.68-1.93) in the peritoneal side subgroup (P = 0.014 for interaction). When we categorized serum IL-6 levels by median value (4.2 pg/mL), the 5-year survival rate of patients with high serum IL-6 levels was significantly higher in the hepatic side subgroup (58.5% vs 14.8%, P < 0.001), but no such difference was found in the peritoneal side subgroup (62.2% vs 67.6%, P = 0.722). CONCLUSIONS: Preoperative serum IL-6 is significantly associated with prognostic implications in patients with hepatic side T2 GBC, not in those with peritoneal side tumors.","Source":"PubMed","category":"HUMAN","training_data":"The association between preoperative serum interleukin-6 levels and postoperative prognosis in patients with T2 gallbladder cancer BACKGROUND: Interleukin-6 (IL-6) is closely associated with tumor progression. Whether it can predict postoperative prognosis of patients with T2 gallbladder cancer (GBC) remains controversial. METHODS: We retrospectively collected the medical records of 125 patients with T2 GBC. Then, we analyzed the association between preoperative serum IL-6 levels and postoperative survival by multivariate Cox analyses and Kaplan-Meier curves in exploratory subgroups. RESULTS: Predictive effects of serum IL-6 levels on overall survival were similar across most of the evaluated subgroups, except in different tumor location subgroups. The independent odds ratio (OR) of serum IL-6 levels was 2.57 (95%CI 1.73-3.82) in the hepatic side subgroup, while it was 1.15 (95%CI 0.68-1.93) in the peritoneal side subgroup (P = 0.014 for interaction). When we categorized serum IL-6 levels by median value (4.2 pg/mL), the 5-year survival rate of patients with high serum IL-6 levels was significantly higher in the hepatic side subgroup (58.5% vs 14.8%, P < 0.001), but no such difference was found in the peritoneal side subgroup (62.2% vs 67.6%, P = 0.722). CONCLUSIONS: Preoperative serum IL-6 is significantly associated with prognostic implications in patients with hepatic side T2 GBC, not in those with peritoneal side tumors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"worldwide burden trends mortality gallbladder biliary tract cancers background aims gallbladder cancer low rate survival unique geographic distribution associated lifestyle factors changed recent decades investigated recent mortality patterns trends worldwide methods collected data world health organization cancer mortality database examine sex specific age standardized rates death gallbladder biliary tract cancers excluding intrahepatic bile duct cancer international classification diseases 9th revision code 156 international classification diseases 10th revision code c23 24 compiled cross sectional rates mortality 2009 2013 50 countries also trends time 1985 2014 using joinpoint regression analysis data 45 countries results among women 2009 2013 26 fold variation rates mortality gallbladder biliary tract cancers rates ranged 0 8 deaths per 100 000 south africa 21 2 deaths per 100 000 chile among men rates varied 16 fold 0 6 deaths per 100 000 united kingdom ireland 9 9 deaths per 100 000 chile rates mortality higher women men 22 48 countries comparison possible mortality rates decreasing countries decreases highest risk populations 2 annually except croatia however rates continued long term increase greece 1 4 annually women 4 7 annually men 1985 2012 began increasing mid 2000s 1 9 annually women united kingdom netherlands men germany conclusions analysis world health organization cancer mortality database found rates death gallbladder biliary tract cancers decreasing countries increasing high income countries following decades decline emerging trends may reflect lifestyle changes increases excess body weight pubmed","probabilities":0.9799733,"Title":"Worldwide Burden of and Trends in Mortality From Gallbladder and Other Biliary Tract Cancers","Abstract":"BACKGROUND & AIMS: Gallbladder cancer has a low rate of survival, a unique geographic distribution, and is associated with lifestyle factors that have changed in recent decades. We investigated recent mortality patterns and trends worldwide. METHODS: We collected data from the World Health Organization's Cancer Mortality Database to examine sex-specific, age-standardized rates of death from gallbladder and other biliary tract cancers (excluding intrahepatic bile duct cancer; International Classification of Diseases, 9th revision, code 156, or International Classification of Diseases, 10th revision, code C23-24). We compiled cross-sectional rates of mortality from 2009 through 2013 from 50 countries, and also trends over time from 1985 through 2014, using joinpoint regression analysis of data from 45 countries. RESULTS: Among women, from 2009 through 2013, there was a 26-fold variation in rates of mortality from gallbladder and other biliary tract cancers; rates ranged from 0.8 deaths per 100,000 in South Africa to 21.2 deaths per 100,000 in Chile. Among men, rates varied 16-fold, from 0.6 deaths per 100,000 in the United Kingdom and Ireland to 9.9 deaths per 100,000 in Chile. Rates of mortality were higher for women than men in 22 of 48 countries for which comparison was possible. Mortality rates are decreasing in most countries, with decreases in the highest-risk populations of 2% or more annually (except Croatia). However, rates continued their long-term increase in Greece, by 1.4% annually in women and 4.7% annually in men from 1985 through 2012, and began increasing in the mid-2000s by 1.9% or more annually in women in the United Kingdom and The Netherlands and in men in Germany. CONCLUSIONS: In an analysis of the World Health Organization's Cancer Mortality Database, we found that rates of death from gallbladder and other biliary tract cancers are decreasing in most countries but increasing in some high-income countries following decades of decline. These emerging trends may reflect lifestyle changes, such as increases in excess body weight.","Source":"PubMed","category":"HUMAN","training_data":"Worldwide Burden of and Trends in Mortality From Gallbladder and Other Biliary Tract Cancers BACKGROUND & AIMS: Gallbladder cancer has a low rate of survival, a unique geographic distribution, and is associated with lifestyle factors that have changed in recent decades. We investigated recent mortality patterns and trends worldwide. METHODS: We collected data from the World Health Organization's Cancer Mortality Database to examine sex-specific, age-standardized rates of death from gallbladder and other biliary tract cancers (excluding intrahepatic bile duct cancer; International Classification of Diseases, 9th revision, code 156, or International Classification of Diseases, 10th revision, code C23-24). We compiled cross-sectional rates of mortality from 2009 through 2013 from 50 countries, and also trends over time from 1985 through 2014, using joinpoint regression analysis of data from 45 countries. RESULTS: Among women, from 2009 through 2013, there was a 26-fold variation in rates of mortality from gallbladder and other biliary tract cancers; rates ranged from 0.8 deaths per 100,000 in South Africa to 21.2 deaths per 100,000 in Chile. Among men, rates varied 16-fold, from 0.6 deaths per 100,000 in the United Kingdom and Ireland to 9.9 deaths per 100,000 in Chile. Rates of mortality were higher for women than men in 22 of 48 countries for which comparison was possible. Mortality rates are decreasing in most countries, with decreases in the highest-risk populations of 2% or more annually (except Croatia). However, rates continued their long-term increase in Greece, by 1.4% annually in women and 4.7% annually in men from 1985 through 2012, and began increasing in the mid-2000s by 1.9% or more annually in women in the United Kingdom and The Netherlands and in men in Germany. CONCLUSIONS: In an analysis of the World Health Organization's Cancer Mortality Database, we found that rates of death from gallbladder and other biliary tract cancers are decreasing in most countries but increasing in some high-income countries following decades of decline. These emerging trends may reflect lifestyle changes, such as increases in excess body weight. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prospective study glycemic load glycemic index carbohydrate intake relation risk biliary tract cancer objectives diets induce high glycemic response might increase risk biliary tract cancer btc evaluated hypothesis diets high glycemic load gl high glycemic index gi measures glycemic effect foods associated increased incidence btc methods used data population based prospective study 76 014 swedish adults age 45 83 years 57 men free cancer completed food frequency questionnaire autumn 1997 incident cancer cases ascertained linkage swedish cancer registry data analyzed using cox proportional hazards regression models results mean follow 13 3 years 1 010 777 person years identified 140 extrahepatic btc cases including 77 gallbladder cancers 23 intrahepatic btc cases high dietary gl associated increased risk btc multivariable relative risks highest versus lowest quartile dietary gl 1 63 95 confidence interval 95 ci 1 01 2 63 extrahepatic btc 2 14 95 ci 1 06 4 33 gallbladder cancer 3 46 95 ci 1 22 9 84 intrahepatic btc dietary gi statistically significantly positively associated risk extrahepatic btc gallbladder cancer observed statistically significant association carbohydrate intake btc risk although associations positive conclusion although data prove causal relationship consistent hypothesis high gl high gi diets associated increased risk btc pubmed","probabilities":0.9799733,"Title":"Prospective Study of Glycemic Load, Glycemic Index, and Carbohydrate Intake in Relation to Risk of Biliary Tract Cancer","Abstract":"OBJECTIVES: Diets that induce a high glycemic response might increase the risk of biliary tract cancer (BTC). We evaluated the hypothesis that diets with high glycemic load (GL) and high glycemic index (GI), which are measures of the glycemic effect of foods, are associated with an increased incidence of BTC. METHODS: We used data from a population-based prospective study of 76,014 Swedish adults (age 45-83 years; 57% men) who were free of cancer and had completed a food-frequency questionnaire in the autumn of 1997. Incident cancer cases were ascertained by linkage with the Swedish Cancer Registry. Data were analyzed using Cox proportional hazards regression models. RESULTS: During a mean follow-up of 13.3 years (1,010,777 person-years), we identified 140 extrahepatic BTC cases (including 77 gallbladder cancers) and 23 intrahepatic BTC cases. A high dietary GL was associated with an increased risk of BTC. The multivariable relative risks for the highest versus lowest quartile of dietary GL were 1.63 (95% confidence interval (95% CI), 1.01-2.63) for extrahepatic BTC, 2.14 (95% CI, 1.06-4.33) for gallbladder cancer, and 3.46 (95% CI, 1.22-9.84) for intrahepatic BTC. Dietary GI was statistically significantly positively associated with risk of extrahepatic BTC and gallbladder cancer. We observed no statistically significant association between carbohydrate intake and BTC risk, although all associations were positive. CONCLUSION: Although these data do not prove a causal relationship, they are consistent with the hypothesis that high-GL and high-GI diets are associated with an increased risk of BTC.","Source":"PubMed","category":"HUMAN","training_data":"Prospective Study of Glycemic Load, Glycemic Index, and Carbohydrate Intake in Relation to Risk of Biliary Tract Cancer OBJECTIVES: Diets that induce a high glycemic response might increase the risk of biliary tract cancer (BTC). We evaluated the hypothesis that diets with high glycemic load (GL) and high glycemic index (GI), which are measures of the glycemic effect of foods, are associated with an increased incidence of BTC. METHODS: We used data from a population-based prospective study of 76,014 Swedish adults (age 45-83 years; 57% men) who were free of cancer and had completed a food-frequency questionnaire in the autumn of 1997. Incident cancer cases were ascertained by linkage with the Swedish Cancer Registry. Data were analyzed using Cox proportional hazards regression models. RESULTS: During a mean follow-up of 13.3 years (1,010,777 person-years), we identified 140 extrahepatic BTC cases (including 77 gallbladder cancers) and 23 intrahepatic BTC cases. A high dietary GL was associated with an increased risk of BTC. The multivariable relative risks for the highest versus lowest quartile of dietary GL were 1.63 (95% confidence interval (95% CI), 1.01-2.63) for extrahepatic BTC, 2.14 (95% CI, 1.06-4.33) for gallbladder cancer, and 3.46 (95% CI, 1.22-9.84) for intrahepatic BTC. Dietary GI was statistically significantly positively associated with risk of extrahepatic BTC and gallbladder cancer. We observed no statistically significant association between carbohydrate intake and BTC risk, although all associations were positive. CONCLUSION: Although these data do not prove a causal relationship, they are consistent with the hypothesis that high-GL and high-GI diets are associated with an increased risk of BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"histologic types ampullary carcinoma frequency clinicopathologic associations 367 cases abstract available google scholar","probabilities":0.9799733,"Title":"Histologic Types Of Ampullary Carcinoma: Frequency And Clinicopathologic Associations In 367 Cases","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Histologic Types Of Ampullary Carcinoma: Frequency And Clinicopathologic Associations In 367 Cases Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"identifying survival associated cerna clusters cholangiocarcinoma competing endogenous rnas cernas represent novel layer regulations long non coding rnas lncrnas genes play important roles cancer pathogenesis binding micrornas mirnas however competition mechanism cernas cholangiocarcinoma chol fully understood study constructed dysregulated cerna competitive network ccen globally characterize competing difference chol normal tissues integrated affinity propagation kaplan meier k m methods identify functional clusters associated survival total 7 key cerna clusters identified functional annotation analyses found cluster23 cluster32 involved cell based functions loss cerna competitive relations clusters may contribute chol disturbing important biological processes pathway cancer mapk neurotrophin signaling pathway study provides insights understanding competitive mechanism cernas chol stn","probabilities":0.9467213,"Title":"Identifying Survival-Associated Cerna Clusters In Cholangiocarcinoma","Abstract":"Competing endogenous RNAs (ceRNAs) represent a novel layer regulations of long non-coding RNAs (lncRNAs) and genes that play important roles in cancer pathogenesis by binding microRNAs (miRNAs). However, the competition mechanism of ceRNAs in cholangiocarcinoma (CHOL) is not fully understood. In this study, we constructed a dysregulated ceRNA competitive network (CCEN) to globally characterize the competing difference between CHOL and normal tissues. Then, we integrated affinity propagation and Kaplan‑Meier (K-M) methods to identify functional clusters associated with survival. A total of 7 key ceRNA clusters were identified. Further functional annotation analyses found that Cluster23 and Cluster32 involved cell based functions, and the loss of ceRNA competitive relations in clusters may contribute to CHOL, by disturbing important biological processes, such as 'Pathway in cancer', MAPK and Neurotrophin signaling pathway. This study provides further insights into understanding the competitive mechanism of ceRNAs in CHOL.","Source":"STN","category":"ANIMAL","training_data":"Identifying Survival-Associated Cerna Clusters In Cholangiocarcinoma Competing endogenous RNAs (ceRNAs) represent a novel layer regulations of long non-coding RNAs (lncRNAs) and genes that play important roles in cancer pathogenesis by binding microRNAs (miRNAs). However, the competition mechanism of ceRNAs in cholangiocarcinoma (CHOL) is not fully understood. In this study, we constructed a dysregulated ceRNA competitive network (CCEN) to globally characterize the competing difference between CHOL and normal tissues. Then, we integrated affinity propagation and Kaplan‑Meier (K-M) methods to identify functional clusters associated with survival. A total of 7 key ceRNA clusters were identified. Further functional annotation analyses found that Cluster23 and Cluster32 involved cell based functions, and the loss of ceRNA competitive relations in clusters may contribute to CHOL, by disturbing important biological processes, such as 'Pathway in cancer', MAPK and Neurotrophin signaling pathway. This study provides further insights into understanding the competitive mechanism of ceRNAs in CHOL. STN","prediction_labels":"ANIMAL"},{"cleaned":"signaling pathways therapeutic targets biliary tract cancer incidence biliary tract cancer btc increasing disease frequently diagnosed advanced stages leading poor overall survival limited treatment options currently available novel therapeutic approaches needed number completed clinical trials evaluated role chemotherapy btc demonstrating marginal benefit thus increased interest applying targeted therapies disease areas covered review article summarizes role chemotherapeutic regimens treatment btc highlights key signal transduction pathways interest targeted inhibition particular interest mek map2k mitogen activated protein kinase kinase phosphatidylinositol 3 kinase pi3k signal transducer activator transcription 3 stat3 pathways discuss available data several promising inhibitors pathways pre clinical clinical settings expert opinion future treatment strategies address targeting mek pi3k stat3 btc focus combined therapeutic approaches pubmed","probabilities":0.9799733,"Title":"Signaling pathways as therapeutic targets in biliary tract cancer","Abstract":"The incidence of biliary tract cancer (BTC) is increasing, and the disease is frequently diagnosed during advanced stages, leading to poor overall survival. Limited treatment options are currently available and novel therapeutic approaches are needed. A number of completed clinical trials have evaluated the role of chemotherapy for BTC, demonstrating a marginal benefit. Thus, there is increased interest in applying targeted therapies for this disease. Areas covered: This review article summarizes the role of chemotherapeutic regimens for the treatment of BTC, and highlights key signal transduction pathways of interest for targeted inhibition. Of particular interest are the MEK or MAP2K (mitogen-activated protein kinase kinase), phosphatidylinositol-3 kinase (PI3K) and signal transducer and activator of transcription-3 (STAT3) pathways. We discuss the available data on several promising inhibitors of these pathways, both in the pre-clinical and clinical settings. Expert opinion: Future treatment strategies should address targeting of MEK, PI3K and STAT3 for BTC, with a focus on combined therapeutic approaches.","Source":"PubMed","category":"HUMAN","training_data":"Signaling pathways as therapeutic targets in biliary tract cancer The incidence of biliary tract cancer (BTC) is increasing, and the disease is frequently diagnosed during advanced stages, leading to poor overall survival. Limited treatment options are currently available and novel therapeutic approaches are needed. A number of completed clinical trials have evaluated the role of chemotherapy for BTC, demonstrating a marginal benefit. Thus, there is increased interest in applying targeted therapies for this disease. Areas covered: This review article summarizes the role of chemotherapeutic regimens for the treatment of BTC, and highlights key signal transduction pathways of interest for targeted inhibition. Of particular interest are the MEK or MAP2K (mitogen-activated protein kinase kinase), phosphatidylinositol-3 kinase (PI3K) and signal transducer and activator of transcription-3 (STAT3) pathways. We discuss the available data on several promising inhibitors of these pathways, both in the pre-clinical and clinical settings. Expert opinion: Future treatment strategies should address targeting of MEK, PI3K and STAT3 for BTC, with a focus on combined therapeutic approaches. PubMed","prediction_labels":"HUMAN"},{"cleaned":"stathmin decreases cholangiocarcinoma cell line sensitivity staurosporine triggered apoptosis via induction erk akt signaling cholangiocarcinoma rare highly fatal malignancy however intrinsic mechanism involved tumorigenesis remains obscure urgent need remains promising target cholangiocarcinoma biological therapies based comparative proteomical technologies found 253 231 different spots gallbladder tumor cell lines cholangiocarcinoma cell lines respectively relative non malignant cells using mass spectrometry ms database searching chose seven differentially expressed proteins high stathmin expression found cholangiocarcinoma gallbladder carcinoma cells stathmin expression validated using immunohistochemistry western blot cholangiocarcinoma tissue samples peritumoral tissue revealed high stathmin expression associated repression staurosporine induced apoptosis cholangiocarcinoma cell moreover found stathmin promoted cancer cell proliferation inhibited apoptosis protein kinase b akt extracellular signal regulated kinase erk signaling integrin 1 appears serve partner stathmin induction erk akt signaling inhibiting apoptosis cholangiocarcinoma cell understanding regulation anti apoptosis effect stathmin might provide new insight overcome therapeutic resistance cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Stathmin Decreases Cholangiocarcinoma Cell Line Sensitivity To Staurosporine-Triggered Apoptosis Via The Induction Of Erk And Akt Signaling","Abstract":"Cholangiocarcinoma is a rare, but highly fatal malignancy. However, the intrinsic mechanism involved in its tumorigenesis remains obscure. An urgent need remains for a promising target for cholangiocarcinoma biological therapies. Based on comparative proteomical technologies, we found 253 and 231 different spots in gallbladder tumor cell lines and cholangiocarcinoma cell lines, respectively, relative to non-malignant cells. Using Mass Spectrometry (MS) and database searching, we chose seven differentially expressed proteins. High Stathmin expression was found in both cholangiocarcinoma and gallbladder carcinoma cells. Stathmin expression was validated using immunohistochemistry and western blot in cholangiocarcinoma tissue samples and peritumoral tissue. It was further revealed that high Stathmin expression was associated with the repression of staurosporine-induced apoptosis in the cholangiocarcinoma cell. Moreover, we found that Stathmin promoted cancer cell proliferation and inhibited its apoptosis through protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) signaling. Integrin, β1 appears to serve as a partner of Stathmin induction of ERK and Akt signaling by inhibiting apoptosis in the cholangiocarcinoma cell. Understanding the regulation of anti-apoptosis effect by Stathmin might provide new insight into how to overcome therapeutic resistance in cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Stathmin Decreases Cholangiocarcinoma Cell Line Sensitivity To Staurosporine-Triggered Apoptosis Via The Induction Of Erk And Akt Signaling Cholangiocarcinoma is a rare, but highly fatal malignancy. However, the intrinsic mechanism involved in its tumorigenesis remains obscure. An urgent need remains for a promising target for cholangiocarcinoma biological therapies. Based on comparative proteomical technologies, we found 253 and 231 different spots in gallbladder tumor cell lines and cholangiocarcinoma cell lines, respectively, relative to non-malignant cells. Using Mass Spectrometry (MS) and database searching, we chose seven differentially expressed proteins. High Stathmin expression was found in both cholangiocarcinoma and gallbladder carcinoma cells. Stathmin expression was validated using immunohistochemistry and western blot in cholangiocarcinoma tissue samples and peritumoral tissue. It was further revealed that high Stathmin expression was associated with the repression of staurosporine-induced apoptosis in the cholangiocarcinoma cell. Moreover, we found that Stathmin promoted cancer cell proliferation and inhibited its apoptosis through protein kinase B (Akt) and extracellular signal-regulated kinase (ERK) signaling. Integrin, β1 appears to serve as a partner of Stathmin induction of ERK and Akt signaling by inhibiting apoptosis in the cholangiocarcinoma cell. Understanding the regulation of anti-apoptosis effect by Stathmin might provide new insight into how to overcome therapeutic resistance in cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"postoperative complications mortality major gastrointestinal surgery background objective incidence postoperative complications death low general population subgroup high risk patients identified amongst adverse postoperative outcomes occur frequently present study undertaken describe incidence postoperative complications length stay mortality major abdominal surgery gastrointestinal hepatobiliary pancreatic malignancies identify risk factors impaired outcome material methods data patients operated gastro intestinal malignancies 2009 2010 retrieved clinical database tartu university hospital major outcome data included incidence postoperative complications hospital 30 day 90 day 1 year mortality length icu hospital stay high risk patients defined patients american society anesthesiologists asa physical status 3 revised cardiac risk index rcri 3 multivariate analysis used determine risk factors postoperative mortality morbidity results total 507 259 men 248 women mean age 68 3 11 3 years operated gastrointestinal hepatobiliary pancreatic malignancies 2009 2010 tartu university hospital department surgical oncology 25 patients classified high risk patients lengths intensive care hospital stay 4 4 7 14 5 10 days respectively rate postoperative complications 33 5 total cohort 44 high risk patients common complication delirium occurred 12 8 patients patients without high risk asa iii rcri 3 hospital 30 90 day 1 year mortality 2 5 12 7 26 0 patients asa iii rcri 3 2 3 hospital mortality 30 90 days 1 year mortality 8 5 17 8 42 2 respectively p 0 001 p 0 0001 p 0 0001 compared lower risk patients multivariate analysis age 70 years asa iii rcri 3 duration surgery 130 min positive fluid balance 1300 ml 1st postoperative day identified independent risk factors development complications conclusion complication rate major gastro intestinal surgery high asa physical status revised cardiac risk index adequately reflect increased risk postoperative complications worse short long term outcome google scholar","probabilities":0.9799733,"Title":"Postoperative Complications And Mortality After Major Gastrointestinal Surgery","Abstract":"Background and objective\nThe incidence of postoperative complications and death is low in the general population, but a subgroup of high-risk patients can be identified amongst whom adverse postoperative outcomes occur more frequently. The present study was undertaken to describe the incidence of postoperative complications, length of stay, and mortality after major abdominal surgery for gastrointestinal, hepatobiliary and pancreatic malignancies and to identify the risk factors for impaired outcome.\nMaterial and methods\nData of patients, operated on for gastro-intestinal malignancies during 2009–2010 were retrieved from the clinical database of Tartu University Hospital. Major outcome data included incidence of postoperative complications, hospital-, 30-day, 90-day and 1-year mortality, and length of ICU and hospital stay. High-risk patients were defined as patients with American Society of Anesthesiologists (ASA) physical status ≥3 and revised cardiac risk index (RCRI) ≥3. Multivariate analysis was used to determine the risk factors for postoperative mortality and morbidity.\nResults\nA total of 507 (259 men and 248 women, mean age 68.3 ± 11.3 years) were operated on for gastrointestinal, hepatobiliary, or pancreatic malignancies during 2009 and 2010 in Tartu University Hospital, Department of Surgical Oncology. 25% of the patients were classified as high risk patients. The lengths of intensive care and hospital stay were 4.4 ± 7 and 14.5 ± 10 days, respectively. The rate of postoperative complications was 33.5% in the total cohort, and 44% in high-risk patients. The most common complication was delirium, which occurred in 12.8% of patients. For patients without high risk (ASA < III; RCRI < 3) in-hospital, 30-, 90-day and 1-year mortality were 2%, 5%, 12.7% and 26.0%. Patients with ASA ≥ III and RCRI ≥ 3 had 2.3% in-hospital mortality, and at 30-, 90 days and 1 year the mortality was 8.5%, 17.8%, and 42.2%, respectively (P = 0.001, P < 0.0001 and P < 0.0001 compared to the lower risk patients). On multivariate analysis, age above 70 years, ASA ≥ III, RCRI ≥ 3, duration of surgery >130 min, and positive fluid balance >1300 mL after the 1st postoperative day, were identified as independent risk factors for the development of complications.\nConclusion\nThe complication rate after major gastro-intestinal surgery is high. ASA physical status and revised cardiac risk index adequately reflect increased risk for postoperative complications and worse short and long-term outcome.","Source":"Google Scholar","category":"HUMAN","training_data":"Postoperative Complications And Mortality After Major Gastrointestinal Surgery Background and objective\nThe incidence of postoperative complications and death is low in the general population, but a subgroup of high-risk patients can be identified amongst whom adverse postoperative outcomes occur more frequently. The present study was undertaken to describe the incidence of postoperative complications, length of stay, and mortality after major abdominal surgery for gastrointestinal, hepatobiliary and pancreatic malignancies and to identify the risk factors for impaired outcome.\nMaterial and methods\nData of patients, operated on for gastro-intestinal malignancies during 2009–2010 were retrieved from the clinical database of Tartu University Hospital. Major outcome data included incidence of postoperative complications, hospital-, 30-day, 90-day and 1-year mortality, and length of ICU and hospital stay. High-risk patients were defined as patients with American Society of Anesthesiologists (ASA) physical status ≥3 and revised cardiac risk index (RCRI) ≥3. Multivariate analysis was used to determine the risk factors for postoperative mortality and morbidity.\nResults\nA total of 507 (259 men and 248 women, mean age 68.3 ± 11.3 years) were operated on for gastrointestinal, hepatobiliary, or pancreatic malignancies during 2009 and 2010 in Tartu University Hospital, Department of Surgical Oncology. 25% of the patients were classified as high risk patients. The lengths of intensive care and hospital stay were 4.4 ± 7 and 14.5 ± 10 days, respectively. The rate of postoperative complications was 33.5% in the total cohort, and 44% in high-risk patients. The most common complication was delirium, which occurred in 12.8% of patients. For patients without high risk (ASA < III; RCRI < 3) in-hospital, 30-, 90-day and 1-year mortality were 2%, 5%, 12.7% and 26.0%. Patients with ASA ≥ III and RCRI ≥ 3 had 2.3% in-hospital mortality, and at 30-, 90 days and 1 year the mortality was 8.5%, 17.8%, and 42.2%, respectively (P = 0.001, P < 0.0001 and P < 0.0001 compared to the lower risk patients). On multivariate analysis, age above 70 years, ASA ≥ III, RCRI ≥ 3, duration of surgery >130 min, and positive fluid balance >1300 mL after the 1st postoperative day, were identified as independent risk factors for the development of complications.\nConclusion\nThe complication rate after major gastro-intestinal surgery is high. ASA physical status and revised cardiac risk index adequately reflect increased risk for postoperative complications and worse short and long-term outcome. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"impact intraluminal brachytherapy survival outcome radiation therapy unresectable biliary tract cancer propensity score matched pair analysis purpose determine whether adding intraluminal brachytherapy ilbt definitive radiation therapy rt unresectable biliary tract cancer positive impact survival outcome methods materials original cohort comprised 209 patients including 153 underwent external beam rt ebrt alone 56 received ilbt ebrt matching propensity scores 56 pairs 112 patients consisting 1 patient 1 patient without ilbt selected well balanced terms sex age performance status clinical stage jaundice addition chemotherapy impact ilbt overall survival os disease specific survival dss local control lc investigated results 2 year os rates 31 ilbt group 40 theilbt group p 862 2 year dss rates 42 ilbt group 41 ilbt group p 288 2 year lc rates 65 ilbt group 35 ilbt group p 094 three 4 sensitivity analyses showed significantly better lc ilbt group p 010 025 049 another showed marginally better lc p 068 none sensitivity analyses showed statistically significant differences os dss conclusions treatment unresectable biliary tract cancer addition ilbt rt impact os dss associated better lc therefore role ilbt addressed measures survival benefit example less toxicity prolonged biliary tract patency decreasing need palliative interventions patient quality life pubmed","probabilities":0.9799733,"Title":"Impact of intraluminal brachytherapy on survival outcome for radiation therapy for unresectable biliary tract cancer: a propensity-score matched-pair analysis","Abstract":"PURPOSE: To determine whether adding intraluminal brachytherapy (ILBT) to definitive radiation therapy (RT) for unresectable biliary tract cancer has a positive impact on survival outcome. METHODS AND MATERIALS: The original cohort comprised 209 patients, including 153 who underwent external beam RT (EBRT) alone and 56 who received both ILBT and EBRT. By matching propensity scores, 56 pairs (112 patients) consisting of 1 patient with and 1 patient without ILBT were selected. They were well balanced in terms of sex, age, performance status, clinical stage, jaundice, and addition of chemotherapy. The impact of ILBT on overall survival (OS), disease-specific survival (DSS), and local control (LC) was investigated. RESULTS: The 2-year OS rates were 31% for the ILBT+ group and 40% for theILBT- group (P=.862). The 2-year DSS rates were 42% for the ILBT+ group and 41% for the ILBT- group (P=.288). The 2-year LC rates were 65% for the ILBT+ group and 35% for the ILBT- group (P=.094). Three of the 4 sensitivity analyses showed a significantly better LC for the ILBT+ group (P=.010, .025, .049), and another showed a marginally better LC (P=.068), and none of the sensitivity analyses showed any statistically significant differences in OS or DSS. CONCLUSIONS: In the treatment for unresectable biliary tract cancer, the addition of ILBT to RT has no impact on OS or DSS but is associated with better LC. Therefore, the role of ILBT should be addressed by other measures than survival benefit, for example, by less toxicity, prolonged biliary tract patency decreasing the need for further palliative interventions, or patient quality of life.","Source":"PubMed","category":"HUMAN","training_data":"Impact of intraluminal brachytherapy on survival outcome for radiation therapy for unresectable biliary tract cancer: a propensity-score matched-pair analysis PURPOSE: To determine whether adding intraluminal brachytherapy (ILBT) to definitive radiation therapy (RT) for unresectable biliary tract cancer has a positive impact on survival outcome. METHODS AND MATERIALS: The original cohort comprised 209 patients, including 153 who underwent external beam RT (EBRT) alone and 56 who received both ILBT and EBRT. By matching propensity scores, 56 pairs (112 patients) consisting of 1 patient with and 1 patient without ILBT were selected. They were well balanced in terms of sex, age, performance status, clinical stage, jaundice, and addition of chemotherapy. The impact of ILBT on overall survival (OS), disease-specific survival (DSS), and local control (LC) was investigated. RESULTS: The 2-year OS rates were 31% for the ILBT+ group and 40% for theILBT- group (P=.862). The 2-year DSS rates were 42% for the ILBT+ group and 41% for the ILBT- group (P=.288). The 2-year LC rates were 65% for the ILBT+ group and 35% for the ILBT- group (P=.094). Three of the 4 sensitivity analyses showed a significantly better LC for the ILBT+ group (P=.010, .025, .049), and another showed a marginally better LC (P=.068), and none of the sensitivity analyses showed any statistically significant differences in OS or DSS. CONCLUSIONS: In the treatment for unresectable biliary tract cancer, the addition of ILBT to RT has no impact on OS or DSS but is associated with better LC. Therefore, the role of ILBT should be addressed by other measures than survival benefit, for example, by less toxicity, prolonged biliary tract patency decreasing the need for further palliative interventions, or patient quality of life. PubMed","prediction_labels":"HUMAN"},{"cleaned":"microrna expression implications diagnosis therapy gallbladder cancer gallbladder cancer common biliary tract malignancy poor prognosis micrornas mirnas class small endogenous non coding rnas 19 23 nucleotides length regulate gene expression post transcriptional translational levels several studies demonstrated aberrant expression mirnas gallbladder cancer tissues recent evidences also demonstrated specific mirnas functionally involved gallbladder cancer development modulating cell proliferation apoptosis migration invasion metastasis review explore possibilities using mirnas prognostic diagnostic markers therapeutic targets gallbladder cancer pubmed","probabilities":0.962963,"Title":"MicroRNA expression and its implications for diagnosis and therapy of gallbladder cancer","Abstract":"Gallbladder cancer is the most common biliary tract malignancy with poor prognosis. MicroRNAs (miRNAs) are a class of small, endogenous, non-coding RNAs of 19-23 nucleotides in length, which regulate gene expression at post-transcriptional and translational levels. Several studies have demonstrated aberrant expression of miRNAs in gallbladder cancer tissues. Recent evidences also demonstrated that specific miRNAs are functionally involved in gallbladder cancer development through modulating cell proliferation, apoptosis, migration, invasion and metastasis. In this review, we explore the possibilities of using miRNAs as prognostic, diagnostic markers and therapeutic targets in gallbladder cancer.","Source":"PubMed","category":"HUMAN","training_data":"MicroRNA expression and its implications for diagnosis and therapy of gallbladder cancer Gallbladder cancer is the most common biliary tract malignancy with poor prognosis. MicroRNAs (miRNAs) are a class of small, endogenous, non-coding RNAs of 19-23 nucleotides in length, which regulate gene expression at post-transcriptional and translational levels. Several studies have demonstrated aberrant expression of miRNAs in gallbladder cancer tissues. Recent evidences also demonstrated that specific miRNAs are functionally involved in gallbladder cancer development through modulating cell proliferation, apoptosis, migration, invasion and metastasis. In this review, we explore the possibilities of using miRNAs as prognostic, diagnostic markers and therapeutic targets in gallbladder cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect adjuvant gemcitabine combined low dose 5 fluorouracil cisplatin chemotherapy advanced biliary carcinoma background aim aim retrospective study clarify effectiveness chemotherapy gemcitabine combined low dose 5 fluorouracil cisplatin gfp advanced biliary carcinoma hepatectomy patients methods sixty two patients biliary carcinoma lymph node metastasis intrahepatic metastasis positive surgical margins including intrahepatic cholangiocarcinoma ihc n 25 hilar cholangiocarcinoma hc n 14 gallbladder cancer gbc n 23 twenty eight patients ihc n 9 hc n 8 gbc n 11 received adjuvant gfp chemotherapy results found significant difference clinicopathological factors patients treated without adjuvant gfp chemotherapy overall survival adjuvant gfp group significantly better non adjuvant gfp group 3 year survival 61 9 vs 8 8 p 0 001 relapse free survival conclusion adjuvant gfp chemotherapy hepatectomy may promising option improving surgical outcomes patients advanced biliary carcinoma pubmed","probabilities":0.9799733,"Title":"Effect of Adjuvant Gemcitabine Combined with Low-dose 5-Fluorouracil and Cisplatin Chemotherapy for Advanced Biliary Carcinoma","Abstract":"BACKGROUND/AIM: The aim of this retrospective study was to clarify the effectiveness of chemotherapy with gemcitabine combined with low-dose 5-fluorouracil and cisplatin (GFP) for advanced biliary carcinoma after hepatectomy. PATIENTS AND METHODS: Sixty-two patients had biliary carcinoma with lymph node metastasis, intrahepatic metastasis or positive surgical margins, including intrahepatic cholangiocarcinoma (IHC, n=25), hilar cholangiocarcinoma (HC, n=14), and gallbladder cancer (GBC, n=23). Twenty-eight patients (IHC; n=9, HC; n=8, GBC; n=11) received adjuvant GFP chemotherapy. RESULTS: We found no significant difference in clinicopathological factors in patients treated with or without adjuvant GFP chemotherapy. Overall, survival in the adjuvant GFP group was significantly better than that in the non-adjuvant GFP group (3-year survival: 61.9% vs. 8.8%, p<0.001), as was relapse-free survival. CONCLUSION: Adjuvant GFP chemotherapy after hepatectomy may be a promising option for improving surgical outcomes in patients with advanced biliary carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Effect of Adjuvant Gemcitabine Combined with Low-dose 5-Fluorouracil and Cisplatin Chemotherapy for Advanced Biliary Carcinoma BACKGROUND/AIM: The aim of this retrospective study was to clarify the effectiveness of chemotherapy with gemcitabine combined with low-dose 5-fluorouracil and cisplatin (GFP) for advanced biliary carcinoma after hepatectomy. PATIENTS AND METHODS: Sixty-two patients had biliary carcinoma with lymph node metastasis, intrahepatic metastasis or positive surgical margins, including intrahepatic cholangiocarcinoma (IHC, n=25), hilar cholangiocarcinoma (HC, n=14), and gallbladder cancer (GBC, n=23). Twenty-eight patients (IHC; n=9, HC; n=8, GBC; n=11) received adjuvant GFP chemotherapy. RESULTS: We found no significant difference in clinicopathological factors in patients treated with or without adjuvant GFP chemotherapy. Overall, survival in the adjuvant GFP group was significantly better than that in the non-adjuvant GFP group (3-year survival: 61.9% vs. 8.8%, p<0.001), as was relapse-free survival. CONCLUSION: Adjuvant GFP chemotherapy after hepatectomy may be a promising option for improving surgical outcomes in patients with advanced biliary carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatic arterial infusion therapy advanced cancer liver predominant disease md anderson experience background aims liver metastases patients cancer associated poor prognosis assessed clinical outcomes patients advanced cancer predominant liver involvement treated hepatic arterial infusion hai chemotherapy protocols methodology retrospectively analyzed outcomes patients referred phase clinical trials program april 2004 september 2009 results overall 202 consecutive patients identified 189 evaluable patients rates partial response pr stable disease sd 4 months 6 3 23 respectively patients hepatocellular carcinoma cholangiocarcinoma n 15 5 33 sd 4 months patients colorectal cancer n 67 treated hal oxaliplatin irinotecan combination therapy rates pr sd 4 months 7 5 34 3 respectively patients breast cancer n 17 treated hai cisplatin based therapy rates pr sd 4 months 17 6 35 3 respectively median survival patients pr sd 4 months 11 6 months independent factors predicting shorter survival male gender decreased albumin hemogloblin elevated bilirubin lactate dehydrogenase alanine aminotransferase conclusions hai combination therapies antitumor activity selected heavily pretreated patients certain tumor types liver involvement pubmed","probabilities":0.9799733,"Title":"Hepatic arterial infusion therapy in advanced cancer and liver-predominant disease: the MD Anderson Experience","Abstract":"BACKGROUND/AIMS: Liver metastases in patients with cancer are associated with a poor prognosis. We assessed the clinical outcomes in patients with advanced cancer and predominant liver involvement treated on hepatic arterial infusion (HAI chemotherapy protocols. METHODOLOGY: We retrospectively analyzed the outcomes of patients referred to the Phase I Clinical Trials Program between April 2004 and September 2009. RESULTS: Overall, 202 consecutive patients were identified. Of 189 evaluable patients, the rates of partial response (PR) and stable disease (SD) >4 months were 6.3% and 23%, respectively. In patients with hepatocellular carcinoma or cholangiocarcinoma (n = 15), 5 (33%) had SD ≥ 4 months. In patients with colorectal cancer (n = 67) treated with HAl oxaliplatin or irinotecan combination therapy, the rates of PR and SD ≥ 4 months were 7.5% and 34.3%, respectively. In patients with breast cancer (n = 17) treated with HAI cisplatin-based therapy, the rates of PR and SD -4 months were 17.6% and 35.3%, respectively. The median survival of patients with PR and SD ≥ 4 months was 11.6 months. Independent factors predicting shorter survival were male gender; decreased albumin and hemogloblin; and elevated bilirubin, lactate dehydrogenase and alanine aminotransferase. CONCLUSIONS: HAI combination therapies have antitumor activity in selected heavily pretreated patients with certain tumor types and liver involvement.","Source":"PubMed","category":"HUMAN","training_data":"Hepatic arterial infusion therapy in advanced cancer and liver-predominant disease: the MD Anderson Experience BACKGROUND/AIMS: Liver metastases in patients with cancer are associated with a poor prognosis. We assessed the clinical outcomes in patients with advanced cancer and predominant liver involvement treated on hepatic arterial infusion (HAI chemotherapy protocols. METHODOLOGY: We retrospectively analyzed the outcomes of patients referred to the Phase I Clinical Trials Program between April 2004 and September 2009. RESULTS: Overall, 202 consecutive patients were identified. Of 189 evaluable patients, the rates of partial response (PR) and stable disease (SD) >4 months were 6.3% and 23%, respectively. In patients with hepatocellular carcinoma or cholangiocarcinoma (n = 15), 5 (33%) had SD ≥ 4 months. In patients with colorectal cancer (n = 67) treated with HAl oxaliplatin or irinotecan combination therapy, the rates of PR and SD ≥ 4 months were 7.5% and 34.3%, respectively. In patients with breast cancer (n = 17) treated with HAI cisplatin-based therapy, the rates of PR and SD -4 months were 17.6% and 35.3%, respectively. The median survival of patients with PR and SD ≥ 4 months was 11.6 months. Independent factors predicting shorter survival were male gender; decreased albumin and hemogloblin; and elevated bilirubin, lactate dehydrogenase and alanine aminotransferase. CONCLUSIONS: HAI combination therapies have antitumor activity in selected heavily pretreated patients with certain tumor types and liver involvement. PubMed","prediction_labels":"HUMAN"},{"cleaned":"screening high risk populations cancer hepatobiliary cancers hepatobiliary tract highly fatal prompting need early detection provide treatment decrease mortality rate screening patients hepatobiliary cancers provide early detection feasible efficient screen patients therefore important consider known risk factors hepatobiliary cancer creates smaller population amenable screening pubmed","probabilities":0.9799733,"Title":"Screening high risk populations for cancer: Hepatobiliary","Abstract":"Cancers of the hepatobiliary tract are highly fatal, prompting the need for early detection to provide treatment and decrease the mortality rate. Screening patients for hepatobiliary cancers can provide early detection, but it is not feasible or efficient to screen all patients. Therefore, it is important to consider the known risk factors for each hepatobiliary cancer which creates a smaller population that is amenable to screening.","Source":"PubMed","category":"HUMAN","training_data":"Screening high risk populations for cancer: Hepatobiliary Cancers of the hepatobiliary tract are highly fatal, prompting the need for early detection to provide treatment and decrease the mortality rate. Screening patients for hepatobiliary cancers can provide early detection, but it is not feasible or efficient to screen all patients. Therefore, it is important to consider the known risk factors for each hepatobiliary cancer which creates a smaller population that is amenable to screening. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative platelet lymphocyte ratio predicts survival patients distal bile duct cancer abstract available google scholar","probabilities":0.9799733,"Title":"Preoperative Platelet Lymphocyte Ratio Predicts Survival In Patients With Distal Bile Duct Cancer","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Preoperative Platelet Lymphocyte Ratio Predicts Survival In Patients With Distal Bile Duct Cancer Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"association variants inflammation cancer associated genes risk survival cholangiocarcinoma genetic risk factors cholangiocarcinoma cca remain poorly understood assessed effect single nucleotide polymorphisms snps genes modulating inflammation carcinogenesis cca risk survival conducted case control candidate gene association study 370 cca patients 740 age sex residential area matched healthy controls eighteen functional putatively functional snps nine genes genotyped log additive genotype effects snps cca risk survival determined using logistic regression log rank test respectively initial analysis identified significant associations snp rs2143417 rs689466 cyclooxygenase 2 cox 2 cca risk adjusting multiple comparisons cutoff p 0 0028 however findings replicated another independent cohort 212 cca cases 424 matched controls significant association found snp survival cca patients although cox 2 shown contribute cholangiocarcinogenesis cox 2 snps tested associated risk cca study shows lack association variants genes related inflammation carcinogenesis cca risk survival factors genetic variants may play important roles cca risk survival pubmed","probabilities":0.9799733,"Title":"Association between variants in inflammation and cancer-associated genes and risk and survival of cholangiocarcinoma","Abstract":"Genetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single-nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case-control, candidate gene association study of 370 CCA patients and 740 age-, sex-, and residential area-matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log-additive genotype effects of SNPs on CCA risk and survival were determined using logistic regression and the log-rank test, respectively. Initial analysis identified significant associations between SNP rs2143417 and rs689466 in cyclooxygenase 2 (COX-2) and CCA risk, after adjusting for multiple comparisons (cutoff of P = 0.0028). However, these findings were not replicated in another independent cohort of 212 CCA cases and 424 matched controls. No significant association was found between any SNP and survival of CCA patients. Although COX-2 has been shown to contribute to cholangiocarcinogenesis, the COX-2 SNPs tested were not associated with risk of CCA. This study shows a lack of association between variants of genes related to inflammation and carcinogenesis and CCA risk and survival. Other factors than these genetic variants may play more important roles in CCA risk and survival.","Source":"PubMed","category":"HUMAN","training_data":"Association between variants in inflammation and cancer-associated genes and risk and survival of cholangiocarcinoma Genetic risk factors for cholangiocarcinoma (CCA) remain poorly understood. We assessed the effect of single-nucleotide polymorphisms (SNPs) of genes modulating inflammation or carcinogenesis on CCA risk and survival. We conducted a case-control, candidate gene association study of 370 CCA patients and 740 age-, sex-, and residential area-matched healthy controls. Eighteen functional or putatively functional SNPs in nine genes were genotyped. The log-additive genotype effects of SNPs on CCA risk and survival were determined using logistic regression and the log-rank test, respectively. Initial analysis identified significant associations between SNP rs2143417 and rs689466 in cyclooxygenase 2 (COX-2) and CCA risk, after adjusting for multiple comparisons (cutoff of P = 0.0028). However, these findings were not replicated in another independent cohort of 212 CCA cases and 424 matched controls. No significant association was found between any SNP and survival of CCA patients. Although COX-2 has been shown to contribute to cholangiocarcinogenesis, the COX-2 SNPs tested were not associated with risk of CCA. This study shows a lack of association between variants of genes related to inflammation and carcinogenesis and CCA risk and survival. Other factors than these genetic variants may play more important roles in CCA risk and survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"fluoropyrimidines plus cisplatin versus gemcitabine gemcitabine plus cisplatin locally advanced metastatic biliary tract carcinoma retrospective study aim retrospective study patients advanced biliary tract carcinoma btc treated different regimens chemotherapy methods studied patients advanced btc registered department oncology fundeni clinical institute 2004 2008 following data analyzed rate response progression free survival pfs first second line chemotherapy overall survival os drug toxicity ninety six patients eligible either advanced intra extrahepatic cholangiocarcinoma gallbladder cancer prior chemotherapy results 96 patients 57 59 4 received fluoropyrimidines fp cisplatin 39 40 6 gemcitabine gem cisplatin median pfs fp cisplatin 5 9 months 95 ci 5 6 9 gem cisplatin 6 3 months 95 ci 5 4 7 1 p 0 661 median os fp cisplatin 10 3 months 95 ci 7 5 13 1 gem cisplatin 9 1 months 95 ci 7 0 11 2 p 0 098 disease progression 46 patients received second line ct gem fp platinum compounds median os patients fp based first line gem cisplatin second line 19 months 95 ci 8 9 29 higher reverse sequence 13 2 months 95 ci 12 14 4 statistically significant p 0 830 patients evaluated toxicities patients 75 5 reported least one adverse event conclusion results direct comparison fp cisplatin gem cisplatin first line treatment show statistical differences terms rate response pfs os however study showed fp cisplatin first line gem based second line therapy gave better os rate pubmed","probabilities":0.9799733,"Title":"Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study","Abstract":"AIM: This is a retrospective study of patients with advanced biliary tract carcinoma (BTC), who were treated with different regimens of chemotherapy. METHODS: We studied patients with advanced BTC registered at the Department of Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following data were analyzed: rate of response, progression free survival (PFS) to first and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety-six patients were eligible having either advanced intra or extrahepatic cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. RESULTS: Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39 (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9 months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661. Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/-cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46 patients received second line CT (Gem or FP+/-platinum compounds). Median OS for patients with FP based first line and Gem+/-cisplatin in second line was 19 months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12-14.4), but not statistically significant (p=0.830). All patients were evaluated for toxicities. Most patients (75.5%) reported at least one adverse event. CONCLUSION: Our results through direct comparison of FP+cisplatin with Gem+/-cisplatin as first line treatment did not show any statistical differences in terms of rate of response, PFS and OS. However, our study showed that FP+cisplatin as first line and Gem based second line therapy gave a better OS rate.","Source":"PubMed","category":"HUMAN","training_data":"Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study AIM: This is a retrospective study of patients with advanced biliary tract carcinoma (BTC), who were treated with different regimens of chemotherapy. METHODS: We studied patients with advanced BTC registered at the Department of Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following data were analyzed: rate of response, progression free survival (PFS) to first and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety-six patients were eligible having either advanced intra or extrahepatic cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. RESULTS: Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39 (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9 months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661. Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/-cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46 patients received second line CT (Gem or FP+/-platinum compounds). Median OS for patients with FP based first line and Gem+/-cisplatin in second line was 19 months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12-14.4), but not statistically significant (p=0.830). All patients were evaluated for toxicities. Most patients (75.5%) reported at least one adverse event. CONCLUSION: Our results through direct comparison of FP+cisplatin with Gem+/-cisplatin as first line treatment did not show any statistical differences in terms of rate of response, PFS and OS. However, our study showed that FP+cisplatin as first line and Gem based second line therapy gave a better OS rate. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tissue specific significance bap1 gene mutation prognostic prediction molecular taxonomy among different types cancer bap1 emerging tumor suppressor whose inactivating mutations found play critical roles tumor development study conducted elucidate potential value bap1 mutation guiding prognostic prediction clinical stratification conducted comprehensive analysis relevant studies multiple databases determine impact bap1 mutation overall survival disease free survival patients various cancers total 2457 patients 21 studies included final analysis although pooled results demonstrated bap1 mutation negative indicator overall survival hazard ratio 1 73 95 confidence interval 1 23 2 42 disease free survival hazard ratio 2 25 95 confidence interval 1 47 3 45 prognostic value applicable uveal melanoma clear cell renal cell carcinoma malignant pleural mesothelioma cholangiocarcinoma consistently bap1 mutation correlated critical clinicopathological features uveal melanoma clear cell renal cell carcinoma uveal melanoma bap1 mutation sf3b1 eif1ax mutations negatively correlated bap1 mutant tumors indicated significant worse prognosis sf3b1 eif1ax mutant tumors p 0 028 clear cell renal cell carcinoma bap1 mutation mutually exclusive pbrm1 mutations bap1 mutant clear cell renal cell carcinomas also showed significantly worse prognosis pbrm1 mutant clear cell renal cell carcinomas p 0 001 study revealed unique tissue specific significance bap1 mutation prognostic prediction among different types cancer clinically combining detection bap1 mutation driver mutations may allow precise molecular taxonomy stratify patients distinct subgroups uveal melanoma clear cell renal cell carcinoma pubmed","probabilities":0.962963,"Title":"Tissue-specific significance of BAP1 gene mutation in prognostic prediction and molecular taxonomy among different types of cancer","Abstract":"BAP1 is an emerging tumor suppressor whose inactivating mutations have been found to play critical roles in tumor development. This study was conducted to elucidate the potential value of BAP1 mutation in guiding prognostic prediction and clinical stratification. We conducted a comprehensive analysis of relevant studies from multiple databases, to determine the impact of BAP1 mutation on the overall survival and disease-free survival of patients in various cancers. A total of 2457 patients from 21 studies were included in the final analysis. Although the pooled results demonstrated that BAP1 mutation was a negative indicator of overall survival (hazard ratio = 1.73; 95% confidence interval = 1.23-2.42) and disease-free survival (hazard ratio = 2.25; 95% confidence interval = 1.47-3.45), this prognostic value was only applicable to uveal melanoma and clear cell renal cell carcinoma, but not to malignant pleural mesothelioma or cholangiocarcinoma. Consistently, BAP1 mutation was correlated with critical clinicopathological features only in uveal melanoma and clear cell renal cell carcinoma. In uveal melanoma, BAP1 mutation and SF3B1/EIF1AX mutations were negatively correlated, and BAP1-mutant tumors indicated significant worse prognosis than SF3B1/EIF1AX-mutant tumors ( p = 0.028). While in clear cell renal cell carcinoma, BAP1 mutation was mutually exclusive with PBRM1 mutations, and BAP1-mutant clear cell renal cell carcinomas also showed significantly worse prognosis than PBRM1-mutant clear cell renal cell carcinomas ( p = 0.001). Our study revealed a unique tissue-specific significance of BAP1 mutation in prognostic prediction among different types of cancer. Clinically, combining detection of BAP1 mutation and other driver mutations may further allow for a more precise molecular taxonomy to stratify patients into distinct subgroups in uveal melanoma and clear cell renal cell carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Tissue-specific significance of BAP1 gene mutation in prognostic prediction and molecular taxonomy among different types of cancer BAP1 is an emerging tumor suppressor whose inactivating mutations have been found to play critical roles in tumor development. This study was conducted to elucidate the potential value of BAP1 mutation in guiding prognostic prediction and clinical stratification. We conducted a comprehensive analysis of relevant studies from multiple databases, to determine the impact of BAP1 mutation on the overall survival and disease-free survival of patients in various cancers. A total of 2457 patients from 21 studies were included in the final analysis. Although the pooled results demonstrated that BAP1 mutation was a negative indicator of overall survival (hazard ratio = 1.73; 95% confidence interval = 1.23-2.42) and disease-free survival (hazard ratio = 2.25; 95% confidence interval = 1.47-3.45), this prognostic value was only applicable to uveal melanoma and clear cell renal cell carcinoma, but not to malignant pleural mesothelioma or cholangiocarcinoma. Consistently, BAP1 mutation was correlated with critical clinicopathological features only in uveal melanoma and clear cell renal cell carcinoma. In uveal melanoma, BAP1 mutation and SF3B1/EIF1AX mutations were negatively correlated, and BAP1-mutant tumors indicated significant worse prognosis than SF3B1/EIF1AX-mutant tumors ( p = 0.028). While in clear cell renal cell carcinoma, BAP1 mutation was mutually exclusive with PBRM1 mutations, and BAP1-mutant clear cell renal cell carcinomas also showed significantly worse prognosis than PBRM1-mutant clear cell renal cell carcinomas ( p = 0.001). Our study revealed a unique tissue-specific significance of BAP1 mutation in prognostic prediction among different types of cancer. Clinically, combining detection of BAP1 mutation and other driver mutations may further allow for a more precise molecular taxonomy to stratify patients into distinct subgroups in uveal melanoma and clear cell renal cell carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"chronically high level tgfb1a induction causes hepatocellular carcinoma cholangiocarcinoma via dominant erk pathway zebrafish liver cancers including hepatocellular carcinoma hcc cholangiocarcinoma cca increased steadily prevalence non alcoholic steatohepatitis nash underlying mechanism transition nash liver cancers remains unclear first employed diet induced nash zebrafish found elevated level satiety hormone leptin induced overexpression tgfb1 developed tgfb1a transgenic zebrafish inducible hepatocyte specific expression interestingly chronically high tgfb1a induction hepatocytes concurrently drive hcc cca molecularly oncogenicity tgfb1 hcc dependent switch dominant activated signaling pathway smad erk hepatocytes concurrent activation smad erk pathways cholangiocytes essential tgfb1 induced cca findings pinpointed novel role tgfb1 central regulator two major types liver cancers also supported human liver disease samples stn","probabilities":1.0,"Title":"Chronically High Level Of Tgfb1A Induction Causes Both Hepatocellular Carcinoma And Cholangiocarcinoma Via A Dominant Erk Pathway In Zebrafish","Abstract":"Liver cancers including both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) have increased steadily with the prevalence of non-alcoholic steatohepatitis (NASH), but the underlying mechanism for the transition from NASH to liver cancers remains unclear. Here we first employed diet-induced NASH zebrafish and found that elevated level of satiety hormone, leptin, induced overexpression of tgfb1. Then we developed tgfb1a transgenic zebrafish for inducible, hepatocyte-specific expression. Interestingly, chronically high tgfb1a induction in hepatocytes could concurrently drive both HCC and CCA. Molecularly, oncogenicity of Tgfb1 in HCC was dependent on the switch of dominant activated signaling pathway from Smad to Erk in hepatocytes while concurrent activation of both Smad and Erk pathways in cholangiocytes was essential for Tgfb1-induced CCA. These findings pinpointed the novel role of Tgfb1 as a central regulator in the two major types of liver cancers, which was also supported by human liver disease samples.","Source":"STN","category":"ANIMAL","training_data":"Chronically High Level Of Tgfb1A Induction Causes Both Hepatocellular Carcinoma And Cholangiocarcinoma Via A Dominant Erk Pathway In Zebrafish Liver cancers including both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) have increased steadily with the prevalence of non-alcoholic steatohepatitis (NASH), but the underlying mechanism for the transition from NASH to liver cancers remains unclear. Here we first employed diet-induced NASH zebrafish and found that elevated level of satiety hormone, leptin, induced overexpression of tgfb1. Then we developed tgfb1a transgenic zebrafish for inducible, hepatocyte-specific expression. Interestingly, chronically high tgfb1a induction in hepatocytes could concurrently drive both HCC and CCA. Molecularly, oncogenicity of Tgfb1 in HCC was dependent on the switch of dominant activated signaling pathway from Smad to Erk in hepatocytes while concurrent activation of both Smad and Erk pathways in cholangiocytes was essential for Tgfb1-induced CCA. These findings pinpointed the novel role of Tgfb1 as a central regulator in the two major types of liver cancers, which was also supported by human liver disease samples. STN","prediction_labels":"ANIMAL"},{"cleaned":"obesity risk cholangiocarcinoma meta analysis number studies shown obesity implicated susceptibility several cancers however association obesity cholangiocarcinoma remains unclear meta analysis aimed quantitatively assess association overweight obesity incidence cholangiocarcinoma literature search performed cohort case control studies published 1996 2013 using pubmed cochrane embase databases studies included reported odds ratios ors corresponding 95 confidence intervals cis cholangiocarcinoma respect obesity overweight normal weight overweight obesity defined body mass index bmi 18 5 24 9 25 29 9 30 kg m 2 respectively excess body weight defined bmi 25 kg m 2 ten studies met inclusion criteria included five cohort five case control studies compared normal weight overweight pooled 1 30 95 ci 1 13 1 49 obesity pooled 1 52 95 ci 1 13 1 89 excess body weight pooled 1 37 95 ci 1 22 1 55 significantly associated cholangiocarcinoma funnel plot revealed evidence publication bias obesity associated increased risk cholangiocarcinoma needs confirmed long term cohort studies pubmed","probabilities":0.9799733,"Title":"Obesity and the risk of cholangiocarcinoma: a meta-analysis","Abstract":"A number of studies have shown that obesity is implicated in the susceptibility to several cancers. However, the association between obesity and cholangiocarcinoma remains unclear. This meta-analysis aimed to quantitatively assess the association between overweight or obesity and the incidence of cholangiocarcinoma. A literature search was performed for cohort and case-control studies published from 1996 to 2013 using PubMed, Cochrane, and EMBASE databases. Studies were included if they reported odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) of cholangiocarcinoma with respect to obesity or overweight. Normal weight, overweight, and obesity were defined when the body mass index (BMI) was 18.5-24.9, 25-29.9, and ≥ 30 kg/m(2), respectively. Excess body weight was defined as BMI ≥ 25 kg/m(2). Ten studies met the inclusion criteria, which included five cohort and five case-control studies. Compared with normal weight, being overweight (pooled OR 1.30, 95 % CI 1.13-1.49), obesity (pooled OR 1.52, 95 % CI 1.13-1.89), and excess body weight (pooled OR 1.37, 95 %CI 1.22-1.55) were significantly associated with cholangiocarcinoma. The funnel plot revealed no evidence for publication bias. Obesity is associated with the increased risk of cholangiocarcinoma, which needs to be confirmed by long-term cohort studies.","Source":"PubMed","category":"HUMAN","training_data":"Obesity and the risk of cholangiocarcinoma: a meta-analysis A number of studies have shown that obesity is implicated in the susceptibility to several cancers. However, the association between obesity and cholangiocarcinoma remains unclear. This meta-analysis aimed to quantitatively assess the association between overweight or obesity and the incidence of cholangiocarcinoma. A literature search was performed for cohort and case-control studies published from 1996 to 2013 using PubMed, Cochrane, and EMBASE databases. Studies were included if they reported odds ratios (ORs) and corresponding 95 % confidence intervals (CIs) of cholangiocarcinoma with respect to obesity or overweight. Normal weight, overweight, and obesity were defined when the body mass index (BMI) was 18.5-24.9, 25-29.9, and ≥ 30 kg/m(2), respectively. Excess body weight was defined as BMI ≥ 25 kg/m(2). Ten studies met the inclusion criteria, which included five cohort and five case-control studies. Compared with normal weight, being overweight (pooled OR 1.30, 95 % CI 1.13-1.49), obesity (pooled OR 1.52, 95 % CI 1.13-1.89), and excess body weight (pooled OR 1.37, 95 %CI 1.22-1.55) were significantly associated with cholangiocarcinoma. The funnel plot revealed no evidence for publication bias. Obesity is associated with the increased risk of cholangiocarcinoma, which needs to be confirmed by long-term cohort studies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect low dose aspirin use survival patients gastrointestinal malignancies observational study background previous studies suggested relationship aspirin use mortality reduction mechanism effect aspirin cancer outcomes remains unclear aim study evaluate aspirin use survival patients gastrointestinal tract cancer methods patients gastrointestinal tract cancer diagnosed 1998 2011 included population based eindhoven cancer registry linked drug dispensing data pharmo database network association aspirin use diagnosis overall survival analysed using cox regression models results total 13 715 patients diagnosed gastrointestinal cancer total 1008 patients identified aspirin users 8278 patients identified nonusers adjusted hazard ratio aspirin users vs nonusers 0 52 95 ci 0 44 0 63 significant association aspirin use survival observed patients oesophageal hepatobiliary colorectal cancer conclusions post diagnosis use aspirin patients gastrointestinal tract malignancies associated increased survival cancers different sites origin biology adds weight hypothesis anti cancer effects aspirin tumour site specific may modulated tumour micro environment google scholar","probabilities":0.9799733,"Title":"Effect Of Low-Dose Aspirin Use On Survival Of Patients With Gastrointestinal Malignancies; An Observational Study","Abstract":"Background: Previous studies suggested a relationship between aspirin use and mortality reduction. The mechanism for the effect of aspirin on cancer outcomes remains unclear. The aim of this study was to evaluate aspirin use and survival in patients with gastrointestinal tract cancer. \nMethods: Patients with gastrointestinal tract cancer diagnosed between 1998 and 2011 were included. The population-based Eindhoven Cancer Registry was linked to drug-dispensing data from the PHARMO Database Network. The association between aspirin use after diagnosis and overall survival was analysed using Cox regression models. \nResults: In total, 13 715 patients were diagnosed with gastrointestinal cancer. A total of 1008 patients were identified as aspirin users, and 8278 patients were identified as nonusers. The adjusted hazard ratio for aspirin users vs nonusers was 0.52 (95% CI 0.44-0.63). A significant association between aspirin use and survival was observed for patients with oesophageal, hepatobiliary and colorectal cancer. \nConclusions: Post-diagnosis use of aspirin in patients with gastrointestinal tract malignancies is associated with increased survival in cancers with different sites of origin and biology. This adds weight to the hypothesis that the anti-cancer effects of aspirin are not tumour-site specific and may be modulated through the tumour micro-environment.","Source":"Google Scholar","category":"HUMAN","training_data":"Effect Of Low-Dose Aspirin Use On Survival Of Patients With Gastrointestinal Malignancies; An Observational Study Background: Previous studies suggested a relationship between aspirin use and mortality reduction. The mechanism for the effect of aspirin on cancer outcomes remains unclear. The aim of this study was to evaluate aspirin use and survival in patients with gastrointestinal tract cancer. \nMethods: Patients with gastrointestinal tract cancer diagnosed between 1998 and 2011 were included. The population-based Eindhoven Cancer Registry was linked to drug-dispensing data from the PHARMO Database Network. The association between aspirin use after diagnosis and overall survival was analysed using Cox regression models. \nResults: In total, 13 715 patients were diagnosed with gastrointestinal cancer. A total of 1008 patients were identified as aspirin users, and 8278 patients were identified as nonusers. The adjusted hazard ratio for aspirin users vs nonusers was 0.52 (95% CI 0.44-0.63). A significant association between aspirin use and survival was observed for patients with oesophageal, hepatobiliary and colorectal cancer. \nConclusions: Post-diagnosis use of aspirin in patients with gastrointestinal tract malignancies is associated with increased survival in cancers with different sites of origin and biology. This adds weight to the hypothesis that the anti-cancer effects of aspirin are not tumour-site specific and may be modulated through the tumour micro-environment. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"molecular pathogenesis gallbladder cancer update gallbladder carcinoma gbc aggressive gastrointestinal malignancy throughout world wide geographical variance subtype biliary tract malignancy poorest prognosis lower survival among biliary tract malignancies various factors associated gbc pathogenesis environmental microbial metabolic molecular chronic inflammation gallbladder due presence gallstone microbial infection eg salmonella h pylori results sustained production inflammatory mediators tissue microenvironment cause genomic changes linked carcinogenesis genetic alterations one major factors associated aggressiveness prognosis researches done explore suitable biomarker early diagnosis identify altered molecular pathways develop appropriate biomarkers early diagnosis therapy predicting prognosis different agents targeted therapy actionable mutations molecules like egfr vegf mtor her2 pdl 1 pd 1 met pi3k n cadherin vegfr mek1 mek2 tried despite advancements dismal improvement survival gbc patients genetic aberrations actionable mutations epigenetic modification including aberrant expressions micro rnas also studied diagnostic biomarker therapeutic targets complex pathogenesis gbc still needs unfolded review focus molecular pathogenesis gbc elucidated till date along future directions explored achieve better management gbc patients pubmed","probabilities":0.7966102,"Title":"Molecular pathogenesis of gallbladder cancer: An update","Abstract":"Gallbladder carcinoma (GBC) is the most aggressive gastrointestinal malignancy throughout the world, with wide geographical variance. It is the subtype of biliary tract malignancy that has the poorest prognosis and lower survival among all biliary tract malignancies. Various factors are associated with GBC pathogenesis such as environmental, microbial, metabolic and molecular. Chronic inflammation of gallbladder due to presence of gallstone or microbial infection (eg. Salmonella or H. pylori) results in sustained production of inflammatory mediators in the tissue microenvironment, which can cause genomic changes linked to carcinogenesis. Genetic alterations are one of the major factors, associated with aggressiveness and prognosis. Researches have been done to explore suitable biomarker for early diagnosis and identify altered molecular pathways to develop appropriate biomarkers for early diagnosis, therapy and predicting prognosis. Different agents for targeted therapy against actionable mutations of molecules like EGFR, VEGF, mTOR, HER2, PDL-1, PD-1, MET, PI3K, N-cadherin, VEGFR, MEK1 and MEK2 are being tried. Despite these advancements, there is dismal improvement in the survival of GBC patients. Genetic aberrations other than actionable mutations and epigenetic modification including aberrant expressions of micro-RNAs, are also being studied both as diagnostic biomarker and therapeutic targets. Complex pathogenesis of GBC still needs to be unfolded. In this review we focus on the molecular pathogenesis of GBC elucidated till date along with future directions that can be explored to achieve better management of GBC patients.","Source":"PubMed","category":"HUMAN","training_data":"Molecular pathogenesis of gallbladder cancer: An update Gallbladder carcinoma (GBC) is the most aggressive gastrointestinal malignancy throughout the world, with wide geographical variance. It is the subtype of biliary tract malignancy that has the poorest prognosis and lower survival among all biliary tract malignancies. Various factors are associated with GBC pathogenesis such as environmental, microbial, metabolic and molecular. Chronic inflammation of gallbladder due to presence of gallstone or microbial infection (eg. Salmonella or H. pylori) results in sustained production of inflammatory mediators in the tissue microenvironment, which can cause genomic changes linked to carcinogenesis. Genetic alterations are one of the major factors, associated with aggressiveness and prognosis. Researches have been done to explore suitable biomarker for early diagnosis and identify altered molecular pathways to develop appropriate biomarkers for early diagnosis, therapy and predicting prognosis. Different agents for targeted therapy against actionable mutations of molecules like EGFR, VEGF, mTOR, HER2, PDL-1, PD-1, MET, PI3K, N-cadherin, VEGFR, MEK1 and MEK2 are being tried. Despite these advancements, there is dismal improvement in the survival of GBC patients. Genetic aberrations other than actionable mutations and epigenetic modification including aberrant expressions of micro-RNAs, are also being studied both as diagnostic biomarker and therapeutic targets. Complex pathogenesis of GBC still needs to be unfolded. In this review we focus on the molecular pathogenesis of GBC elucidated till date along with future directions that can be explored to achieve better management of GBC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"dihydroartemisinin induces apoptosis autophagy dependent cell death cholangiocarcinoma dapk1 beclin1 pathway cholangiocarcinoma cca aggressive cancer arising malignant transformation cholangiocytes intrahepatic cca associated reactive inflammation intense fibrosis hepatobiliary tract dihydroartemisinin dha active compound found artemisia annua shown possess anti tumor activity variety human cancers including hepatoma tested ability dha specifically kill cca cells investigated underlying mechanisms dha induced apoptosis autophagy dependent caspase independent cell death many cca cell lines slightly toxic immortalized cholangiocytes dha induced expression many apoptosis autophagy related genes cca cells particular greatly induced expression dapk1 reduced interaction beclin1 bcl 2 promoting interaction pi3kc3 genetic silencing dapk1 prevented dha induced autophagy pharmacologic genetic inhibition beclin1 function prevented autophagy cell death induced dha cca cells data unravel novel pathway dha cancer toxicity open possibility introduce dha therapeutic regimen treatment cca stn","probabilities":0.9467213,"Title":"Dihydroartemisinin Induces Apoptosis And Autophagy-Dependent Cell Death In Cholangiocarcinoma Through A Dapk1-Beclin1 Pathway","Abstract":"Cholangiocarcinoma (CCA) is a very aggressive cancer arising from the malignant transformation of cholangiocytes. Intrahepatic CCA is associated with reactive inflammation and intense fibrosis of the hepatobiliary tract. Dihydroartemisinin (DHA), the active compound found in Artemisia annua, has been shown to possess anti-tumor activity in a variety of human cancers, including hepatoma. Here, we tested the ability of DHA to specifically kill CCA cells and have investigated the underlying mechanisms. DHA induced both apoptosis and autophagy-dependent caspase-independent cell death in many CCA cell lines, while being slightly toxic to immortalized cholangiocytes. DHA induced the expression of many apoptosis- and autophagy-related genes in CCA cells. In particular, it greatly induced the expression of DAPK1, and reduced the interaction of BECLIN1 with BCL-2 while promoting its interaction with PI3KC3. Genetic silencing of DAPK1 prevented DHA-induced autophagy. Pharmacologic and genetic inhibition of BECLIN1 function prevented autophagy and cell death induced by DHA in CCA cells. These data unravel a novel pathway of DHA cancer toxicity and open the possibility to introduce DHA in the therapeutic regimen for the treatment of CCA.","Source":"STN","category":"ANIMAL","training_data":"Dihydroartemisinin Induces Apoptosis And Autophagy-Dependent Cell Death In Cholangiocarcinoma Through A Dapk1-Beclin1 Pathway Cholangiocarcinoma (CCA) is a very aggressive cancer arising from the malignant transformation of cholangiocytes. Intrahepatic CCA is associated with reactive inflammation and intense fibrosis of the hepatobiliary tract. Dihydroartemisinin (DHA), the active compound found in Artemisia annua, has been shown to possess anti-tumor activity in a variety of human cancers, including hepatoma. Here, we tested the ability of DHA to specifically kill CCA cells and have investigated the underlying mechanisms. DHA induced both apoptosis and autophagy-dependent caspase-independent cell death in many CCA cell lines, while being slightly toxic to immortalized cholangiocytes. DHA induced the expression of many apoptosis- and autophagy-related genes in CCA cells. In particular, it greatly induced the expression of DAPK1, and reduced the interaction of BECLIN1 with BCL-2 while promoting its interaction with PI3KC3. Genetic silencing of DAPK1 prevented DHA-induced autophagy. Pharmacologic and genetic inhibition of BECLIN1 function prevented autophagy and cell death induced by DHA in CCA cells. These data unravel a novel pathway of DHA cancer toxicity and open the possibility to introduce DHA in the therapeutic regimen for the treatment of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"salmonella enterica serovar typhi associated carcinoma gall bladder introduction gallbladder carcinoma common hepatobiliary malignancy poor prognosis 3rd commonest malignancy north india salmonella typhi one risk factor gallbladder cancer india high endemic area typhoid world various authors reported association two without testing typhoid carrier association proven aim present study designed explore association chronic typhoid carrier state carcinoma gall bladder detecting salmonella typhi specimens gallbladder patients malignant benign gallbladder diseases using nested pcr methods material prospective case control study got 39 samples carcinoma gall bladder gbc patients cases 75 samples benign gall bladder diseases gbd patients controls two years duration done indirect haemagglutination test typhoid carrier five milliliters blood collected patient surgery nested pcr done gall bladder tissue taken operation gbc gbd patients result nested pcr showed 59 positivity salmonella typhi gbc 56 gbd association salmonella typhi gbc statistically significant vi antibody present 33 gbc 37 gbd iha also statistically significant conclusion large number sample size require proving association carcinoma gall bladder salmonella typhi using definite marker vi antibodies google scholar","probabilities":0.7966102,"Title":"Is Salmonella Enterica Serovar Typhi Associated With Carcinoma Gall Bladder?","Abstract":"Introduction: Gallbladder carcinoma is a common hepatobiliary malignancy with poor prognosis. It is 3rd commonest malignancy in north India. Salmonella typhi is one of risk factor for gallbladder cancer. India is high endemic area for typhoid in the world. Various authors reported association between the two but without doing testing for typhoid carrier, association cannot be proven. Aim: The present study was designed to explore the association of the chronic typhoid carrier state and carcinoma gall bladder by detecting Salmonella typhi in specimens of gallbladder from patients with malignant and benign gallbladder diseases using a Nested PCR. Methods and material: In this prospective case control study, we have got 39 samples from Carcinoma Gall Bladder (GBC) patients as cases and 75 samples from benign Gall Bladder Diseases (GBD) patients as controls in two years duration. We have done Indirect haemagglutination test for typhoid carrier from five milliliters of blood which was collected from each patient before surgery. Nested PCR was done from gall bladder tissue, which was taken at operation, from both GBC and GBD patients. Result: Nested PCR showed 59% positivity for Salmonella typhi in the GBC and 56% in GBD, so association of Salmonella typhi with GBC was not statistically significant. Vi antibody was present 33% in GBC and 37% in GBD by IHA. It is also not statistically significant. Conclusion: A large number of sample size is require for proving association between carcinoma gall bladder and Salmonella typhi by using definite marker for Vi antibodies","Source":"Google Scholar","category":"HUMAN","training_data":"Is Salmonella Enterica Serovar Typhi Associated With Carcinoma Gall Bladder? Introduction: Gallbladder carcinoma is a common hepatobiliary malignancy with poor prognosis. It is 3rd commonest malignancy in north India. Salmonella typhi is one of risk factor for gallbladder cancer. India is high endemic area for typhoid in the world. Various authors reported association between the two but without doing testing for typhoid carrier, association cannot be proven. Aim: The present study was designed to explore the association of the chronic typhoid carrier state and carcinoma gall bladder by detecting Salmonella typhi in specimens of gallbladder from patients with malignant and benign gallbladder diseases using a Nested PCR. Methods and material: In this prospective case control study, we have got 39 samples from Carcinoma Gall Bladder (GBC) patients as cases and 75 samples from benign Gall Bladder Diseases (GBD) patients as controls in two years duration. We have done Indirect haemagglutination test for typhoid carrier from five milliliters of blood which was collected from each patient before surgery. Nested PCR was done from gall bladder tissue, which was taken at operation, from both GBC and GBD patients. Result: Nested PCR showed 59% positivity for Salmonella typhi in the GBC and 56% in GBD, so association of Salmonella typhi with GBC was not statistically significant. Vi antibody was present 33% in GBC and 37% in GBD by IHA. It is also not statistically significant. Conclusion: A large number of sample size is require for proving association between carcinoma gall bladder and Salmonella typhi by using definite marker for Vi antibodies Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"ceacam6 expression gallbladder carcinoma background gallbladder cancer common biliary tract cancer dismal survival ceacam6 membrane protein involved cell adhesion signaling overexpressed pancreatic biliary adenocarcinoma associated poor prognosis study examines signi cance ceacam6 expression gallbladder cancer relationship outcome methods tissue microarrays containing triplicate cores paraf n embedded surgical specimens patients gallbladder cancer control tissue probed ceacam6 immunohistochemistry clinical pathologic survival data analyzed correlated ceacam6 expression results 70 cases gallbladder cancer 1992 2007 assembled tissue microarrays included 1 t1 1 15 t2 22 51 t3 75 1 t4 1 tumors 4 stage 1 6 44 stage 2 64 1 stage 3 1 20 stage 4 29 patients positive ceacam6 signal present 37 70 53 tumors none control tissues overall median survival 17 months ceacam6 staining correlate age sex grade differentiation positive lymph nodes vascular invasion metastases associated margin positive resection p 0 008 higher ajcc stage p 0 02 survival analysis patients curative r0 resection demonstrated ceacam6 expression associated disease speci c survival 19 months positive vs 25 months negative p 0 5 conclusions ceacam6 prognostic factor resected gallbladder carcinoma however may serve marker aggressive disease google scholar","probabilities":1.0,"Title":"Ceacam6 Expression In Gallbladder Carcinoma","Abstract":"Background: Gallbladder cancer is the most common biliary tract cancer with a dismal survival. CEACAM6 is a membrane protein involved in cell adhesion and signaling that is overexpressed in both pancreatic and biliary adenocarcinoma and associated with a poor prognosis. This study examines the signifi cance of CEACAM6 expression in gallbladder cancer and its relationship to outcome. Methods: Tissue microarrays containing triplicate cores of paraffi n-embedded surgical specimens from patients with gallbladder cancer and control tissue were probed for CEACAM6 by immunohistochemistry. Clinical, pathologic and survival data were analyzed and correlated with CEACAM6 expression. Results: 70 cases of gallbladder cancer from 1992 to 2007 were assembled in the tissue microarrays. They included 1 T1 (1%), 15 T2 (22%), 51 T3 (75%), 1 T4 (1%), tumors and 4 Stage 1 (6%), 44 Stage 2 (64%), 1 Stage 3 (1%), 20 Stage 4 (29%) patients. Positive CEACAM6 signal was present in 37/70 (53%) tumors and none of the control tissues. Overall median survival was 17 months. CEACAM6 staining did not correlate with age, sex, grade of differentiation, positive lymph nodes, vascular invasion or metastases but was associated with margin positive resection (p < 0.008) and higher AJCC stage (p < 0.02). Survival analysis of patients who had a curative or R0 resection demonstrated that CEACAM6 expression was not associated with disease-specifi c survival (19 months for positive vs 25 months for negative, p < 0.5). Conclusions: CEACAM6 is a not prognostic factor in resected gallbladder carcinoma. However, it may serve as a marker of more aggressive disease.","Source":"Google Scholar","category":"ANIMAL","training_data":"Ceacam6 Expression In Gallbladder Carcinoma Background: Gallbladder cancer is the most common biliary tract cancer with a dismal survival. CEACAM6 is a membrane protein involved in cell adhesion and signaling that is overexpressed in both pancreatic and biliary adenocarcinoma and associated with a poor prognosis. This study examines the signifi cance of CEACAM6 expression in gallbladder cancer and its relationship to outcome. Methods: Tissue microarrays containing triplicate cores of paraffi n-embedded surgical specimens from patients with gallbladder cancer and control tissue were probed for CEACAM6 by immunohistochemistry. Clinical, pathologic and survival data were analyzed and correlated with CEACAM6 expression. Results: 70 cases of gallbladder cancer from 1992 to 2007 were assembled in the tissue microarrays. They included 1 T1 (1%), 15 T2 (22%), 51 T3 (75%), 1 T4 (1%), tumors and 4 Stage 1 (6%), 44 Stage 2 (64%), 1 Stage 3 (1%), 20 Stage 4 (29%) patients. Positive CEACAM6 signal was present in 37/70 (53%) tumors and none of the control tissues. Overall median survival was 17 months. CEACAM6 staining did not correlate with age, sex, grade of differentiation, positive lymph nodes, vascular invasion or metastases but was associated with margin positive resection (p < 0.008) and higher AJCC stage (p < 0.02). Survival analysis of patients who had a curative or R0 resection demonstrated that CEACAM6 expression was not associated with disease-specifi c survival (19 months for positive vs 25 months for negative, p < 0.5). Conclusions: CEACAM6 is a not prognostic factor in resected gallbladder carcinoma. However, it may serve as a marker of more aggressive disease.\n Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"prognostic significance stem progenitor cell markers biliary tract carcinoma association two markers better patient survival background hepatobiliary tract one rare examples disease immunophenotypic resemblance stem cells portends worse survival sought examine prognostic significance stem progenitor cell markers biliary tract carcinoma including intra extra hepatic cases design genes interest first chosen based literature search list restricted based gene prognostic significance mrna level cancer genome atlas tcga cohort final genes interest examined protein level cohort biliary tract carcinoma immunohistochemistry ihc previously characterized cohort 163 cases core scored 0 8 combining ihc intensity frequency staining survival analyses performed using kaplan meier method examining disease free recurrence free rfs overall survival os results six genes lgr5 thy1 cd90 pdgfrb cd140b mcam cd146 itgb1 cd29 susd2 chosen genes interest based prognostic values gene expression levels mrna genes examined protein level ihc prognostic significance two proteins met statistically significance namely lgr5 log rank p 0 0007 os rfs cd90 log rank p 0 0007 os lgr5 cd90 protein levels correlated positively one another spearman rho 0 6212 p 0 0001 significant differences either lgr5 cd90 protein levels comparison disease stage patient sex patient age interestingly stronger expression lgr5 cd90 portended better survival protein mrna analyses strong lgr5 expression remained statistically significant os multivariate analysis included cd90 disease stage stage ii vs iii iv anatomic site risk ratio high lgr5 expression 0 5506 95 range 0 3298 0 9085 conclusions immunophenotypic resemblance stem progenitor cells cholangiocarcinoma form strong lgr5 cd90 expression associated better patient survival biologic significance findings remains explored google scholar","probabilities":0.54545456,"Title":"Prognostic Significance Of Stem/Progenitor Cell Markers In Biliary Tract Carcinoma: Association Of Two Markers With Better Patient Survival","Abstract":"Background: Hepatobiliary tract is one of the rare examples of a disease where immunophenotypic resemblance to stem cells portends worse survival. We sought to further examine the prognostic significance of stem/progenitor cell markers in biliary tract carcinoma, including intra- and extra-hepatic cases. Design: Genes of interest were first chosen based on literature search. The list was restricted based on each gene’s prognostic significance at the mRNA level in the Cancer Genome Atlas (TCGA) cohort. Final genes of interest were examined at the protein level in our cohort of biliary tract carcinoma by immunohistochemistry (IHC) in our previously characterized cohort of 163 cases. Each core was scored 0-8, combining the IHC intensity and frequency of staining. Survival analyses were performed using the Kaplan-Meier method, examining both disease-free/recurrence-free (RFS) and overall survival (OS). \nResults: Six genes, LGR5, THY1 (CD90), PDGFRB (CD140b), MCAM (CD146), ITGB1 (CD29) and SUSD2, were chosen as genes of interest based on the prognostic values of their gene expression levels (mRNA). These genes were examined at the protein level by IHC, and the prognostic significance of two proteins met statistically significance, namely LGR5 (log-rank p = 0.0007 for OS or RFS) and CD90 (log-rank p = 0.0007 for OS only). LGR5 and CD90 protein levels correlated positively with one another (Spearman rho = 0.6212, p < 0.0001). There were no significant differences in either LGR5 or CD90 protein levels in comparison to disease stage, patient sex or patient age. Interestingly, stronger expression of LGR5 or CD90 portended better survival by both protein and mRNA analyses. Strong LGR5 expression remained statistically significant for OS in a multivariate analysis that included CD90, disease stage (stage I/II vs. III/IV) and anatomic site (risk ratio for high LGR5 expression = 0.5506, 95% range 0.3298-0.9085). \nConclusions: Immunophenotypic resemblance to stem/progenitor cells in cholangiocarcinoma, in the form of strong LGR5 or CD90 expression, was associated with better patient survival. The biologic significance of these findings remains to be further explored.","Source":"Google Scholar","category":"ANIMAL","training_data":"Prognostic Significance Of Stem/Progenitor Cell Markers In Biliary Tract Carcinoma: Association Of Two Markers With Better Patient Survival Background: Hepatobiliary tract is one of the rare examples of a disease where immunophenotypic resemblance to stem cells portends worse survival. We sought to further examine the prognostic significance of stem/progenitor cell markers in biliary tract carcinoma, including intra- and extra-hepatic cases. Design: Genes of interest were first chosen based on literature search. The list was restricted based on each gene’s prognostic significance at the mRNA level in the Cancer Genome Atlas (TCGA) cohort. Final genes of interest were examined at the protein level in our cohort of biliary tract carcinoma by immunohistochemistry (IHC) in our previously characterized cohort of 163 cases. Each core was scored 0-8, combining the IHC intensity and frequency of staining. Survival analyses were performed using the Kaplan-Meier method, examining both disease-free/recurrence-free (RFS) and overall survival (OS). \nResults: Six genes, LGR5, THY1 (CD90), PDGFRB (CD140b), MCAM (CD146), ITGB1 (CD29) and SUSD2, were chosen as genes of interest based on the prognostic values of their gene expression levels (mRNA). These genes were examined at the protein level by IHC, and the prognostic significance of two proteins met statistically significance, namely LGR5 (log-rank p = 0.0007 for OS or RFS) and CD90 (log-rank p = 0.0007 for OS only). LGR5 and CD90 protein levels correlated positively with one another (Spearman rho = 0.6212, p < 0.0001). There were no significant differences in either LGR5 or CD90 protein levels in comparison to disease stage, patient sex or patient age. Interestingly, stronger expression of LGR5 or CD90 portended better survival by both protein and mRNA analyses. Strong LGR5 expression remained statistically significant for OS in a multivariate analysis that included CD90, disease stage (stage I/II vs. III/IV) and anatomic site (risk ratio for high LGR5 expression = 0.5506, 95% range 0.3298-0.9085). \nConclusions: Immunophenotypic resemblance to stem/progenitor cells in cholangiocarcinoma, in the form of strong LGR5 or CD90 expression, was associated with better patient survival. The biologic significance of these findings remains to be further explored. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"effect smoking risk gallbladder cancer meta analysis observational studies background cigarette smoking shown cause many nonpulmonary cancers including liver pancreas bladder however results epidemiologic studies examining association smoking gallbladder cancer gbc mixed clarify association cigarette smoking gbc performed meta analysis observational studies methods literature search performed using medline 1 january 1966 embase 1 january 1974 31 january 2012 manually searching reference lists pertinent articles summary relative risks srrs corresponding 95 confidence intervals cis calculated random effects model results total 11 articles 10 case control one prospective cohort studies used meta analysis based total 1178 gbc cases analysis 11 studies found smokers increased risk gbc development compared nonsmokers srrs 1 45 95 cis 1 11 1 89 moderate heterogeneity among studies q 18 15 p 0 052 i2 44 9 increased risks independent alcohol use history gallstones significant publication bias found conclusion although current evidence supports positive link cigarette smoking risk gallbladder cancer additional population based studies particularly cohort studies needed definitive conclusions drawn pubmed","probabilities":0.9799733,"Title":"The effect of smoking on the risk of gallbladder cancer: a meta-analysis of observational studies","Abstract":"BACKGROUND: Cigarette smoking has been shown to cause many nonpulmonary cancers, including those of liver, pancreas and bladder. However, results of epidemiologic studies examining the association between smoking and gallbladder cancer (GBC) have been mixed. To clarify the association of cigarette smoking and GBC, we performed a meta-analysis of observational studies. METHODS: A literature search was performed using Medline (from 1 January 1966) and Embase (from 1 January 1974), through 31 January 2012, and by manually searching the reference lists of pertinent articles. Summary relative risks (SRRs) with corresponding 95% confidence intervals (CIs) were calculated with a random-effects model. RESULTS: A total of 11 articles (10 case-control and one prospective cohort studies) were used in this meta-analysis, which is based on a total of 1178 GBC cases. Analysis of 11 studies found that smokers had an increased risk of GBC development, compared with nonsmokers (SRRs 1.45, 95% CIs, 1.11-1.89). There was moderate heterogeneity among studies (Q=18.15, P=0.052, I2 =44.9%). These increased risks were independent of alcohol use and a history of gallstones. No significant publication bias was found. CONCLUSION: Although the current evidence supports a positive link between cigarette smoking and risk of gallbladder cancer, additional population-based studies, particularly cohort studies, are needed before definitive conclusions can be drawn.","Source":"PubMed","category":"HUMAN","training_data":"The effect of smoking on the risk of gallbladder cancer: a meta-analysis of observational studies BACKGROUND: Cigarette smoking has been shown to cause many nonpulmonary cancers, including those of liver, pancreas and bladder. However, results of epidemiologic studies examining the association between smoking and gallbladder cancer (GBC) have been mixed. To clarify the association of cigarette smoking and GBC, we performed a meta-analysis of observational studies. METHODS: A literature search was performed using Medline (from 1 January 1966) and Embase (from 1 January 1974), through 31 January 2012, and by manually searching the reference lists of pertinent articles. Summary relative risks (SRRs) with corresponding 95% confidence intervals (CIs) were calculated with a random-effects model. RESULTS: A total of 11 articles (10 case-control and one prospective cohort studies) were used in this meta-analysis, which is based on a total of 1178 GBC cases. Analysis of 11 studies found that smokers had an increased risk of GBC development, compared with nonsmokers (SRRs 1.45, 95% CIs, 1.11-1.89). There was moderate heterogeneity among studies (Q=18.15, P=0.052, I2 =44.9%). These increased risks were independent of alcohol use and a history of gallstones. No significant publication bias was found. CONCLUSION: Although the current evidence supports a positive link between cigarette smoking and risk of gallbladder cancer, additional population-based studies, particularly cohort studies, are needed before definitive conclusions can be drawn. PubMed","prediction_labels":"HUMAN"},{"cleaned":"high level integrin 6 expression human intrahepatic cholangiocarcinoma cells associated migratory invasive phenotype background integrin 6 subunit part integrin 6 1 6 4 complexes known mediate invasion carcinoma cells however precise role integrin 6 intrahepatic cholangiocarcinoma icc yet addressed methods twenty cases iccs matched nontumor samples used analyze integrin 6 expression immunohistochemistry expression integrin 6 determined rt pcr western blot icc cells regulated expression integrin 6 icc cells specific vshrna integrin 6 assessed role integrin 6 proliferation metastasis invasion icc cells finally involved mechanisms clinical significance investigated results expression integrin 6 icc tissues much higher nontumor samples high level integrin 6 detected icc cells compared normal liver cells hepg2 cells regulation integrin 6 hccc 9810 cells showed ability icc cells metastasize invade much decreased vitro cell proliferation inhibited significantly study indicated high expression integrin 6 enhanced activation erk1 2 akt signals icc cells inhibition erk1 2 regulated icc cell proliferation inhibition akt markedly impaired icc cell metastasis invasion integrin 6 overexpression significantly correlated larger tumors multiple nodular microvascular bile duct invasion lymphatic metastasis p 0 05 postoperative 5 year overall survival os rate patients integrin 6 low higher integrin 6 high group conclusions overexpression integrin 6 associated migratory invasive phenotype icc integrin 6 may used molecular target therapy icc pubmed","probabilities":1.0,"Title":"A high level of integrin α6 expression in human intrahepatic cholangiocarcinoma cells is associated with a migratory and invasive phenotype","Abstract":"BACKGROUND: The integrin α6 subunit is part of the integrin α6β1 and α6β4 complexes, which are known to mediate the invasion of carcinoma cells. However, the precise role of integrin α6 in intrahepatic cholangiocarcinoma (ICC) has not yet been addressed. METHODS: Twenty cases of ICCs and matched nontumor samples were used to analyze integrin α6 expression by immunohistochemistry. After the expression of integrin α6 was determined by RT-PCR and Western blot in ICC cells, we regulated the expression of integrin α6 in ICC cells with specific vshRNA-integrin α6, and assessed the role of integrin α6 in the proliferation and metastasis/invasion of ICC cells. Finally, the involved mechanisms and clinical significance were further investigated. RESULTS: The expression of integrin α6 in ICC tissues was much higher than that in nontumor samples, and the high level of integrin α6 was detected in ICC cells compared with normal liver cells and HepG2 cells. After the down-regulation of integrin α6 in HCCC-9810 cells, we showed that the ability of ICC cells to metastasize and invade was much decreased in vitro, and cell proliferation was inhibited significantly. Further study indicated high expression of integrin α6 enhanced the activation of ERK1/2 and AKT signals in ICC cells and the inhibition of ERK1/2 down-regulated ICC cell proliferation, while the inhibition of AKT markedly impaired ICC cell metastasis and invasion. Integrin α6 overexpression was significantly correlated with larger tumors, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (p < 0.05). The postoperative 5-year overall survival (OS) rate in patients with integrin α6(low) was higher than that of the integrin α6(high) group. CONCLUSIONS: Overexpression of integrin α6 is associated with a migratory and invasive phenotype of ICC, and integrin α6 may be used as molecular target for therapy of ICC.","Source":"PubMed","category":"ANIMAL","training_data":"A high level of integrin α6 expression in human intrahepatic cholangiocarcinoma cells is associated with a migratory and invasive phenotype BACKGROUND: The integrin α6 subunit is part of the integrin α6β1 and α6β4 complexes, which are known to mediate the invasion of carcinoma cells. However, the precise role of integrin α6 in intrahepatic cholangiocarcinoma (ICC) has not yet been addressed. METHODS: Twenty cases of ICCs and matched nontumor samples were used to analyze integrin α6 expression by immunohistochemistry. After the expression of integrin α6 was determined by RT-PCR and Western blot in ICC cells, we regulated the expression of integrin α6 in ICC cells with specific vshRNA-integrin α6, and assessed the role of integrin α6 in the proliferation and metastasis/invasion of ICC cells. Finally, the involved mechanisms and clinical significance were further investigated. RESULTS: The expression of integrin α6 in ICC tissues was much higher than that in nontumor samples, and the high level of integrin α6 was detected in ICC cells compared with normal liver cells and HepG2 cells. After the down-regulation of integrin α6 in HCCC-9810 cells, we showed that the ability of ICC cells to metastasize and invade was much decreased in vitro, and cell proliferation was inhibited significantly. Further study indicated high expression of integrin α6 enhanced the activation of ERK1/2 and AKT signals in ICC cells and the inhibition of ERK1/2 down-regulated ICC cell proliferation, while the inhibition of AKT markedly impaired ICC cell metastasis and invasion. Integrin α6 overexpression was significantly correlated with larger tumors, multiple nodular, microvascular/bile duct invasion, and lymphatic metastasis (p < 0.05). The postoperative 5-year overall survival (OS) rate in patients with integrin α6(low) was higher than that of the integrin α6(high) group. CONCLUSIONS: Overexpression of integrin α6 is associated with a migratory and invasive phenotype of ICC, and integrin α6 may be used as molecular target for therapy of ICC. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"perioperative management hilar cholangiocarcinoma background cholangiocarcinoma common primary tumor biliary tract although accounts 2 human malignancies herein review hilar cholangiocarcinoma including risk factors main classification systems tumors current surgical management disease role chemotherapy liver transplantation may play selected patients methods performed comprehensive literature search using pubmed medline cochrane library period 1980 2015 using following mesh terms hilar cholangiocarcinoma biliary cancer cholangiocarcinoma recent studies published english peer reviewed journals included findings hilar cholangiocarcinoma disease advanced age unclear etiology frequently found southeast asia relatively rare western countries best chance long term survival potential cure surgical resection negative surgical margins many patients unresectable due locally advanced metastatic disease diagnosis result recent efforts new methods management identified patients including preoperative portal vein embolism biliary drainage neoadjuvant chemotherapy subsequent transplantation chemoradiation therapy conclusion current management hilar cholangiocarcinoma depends extent tumor presentation includes surgical resection liver transplantation portal vein embolization chemoradiation therapy understanding hilar cholangiocarcinoma improved recent years research offers hope improve outcome patients rare tumors pubmed","probabilities":0.8684211,"Title":"Perioperative Management of Hilar Cholangiocarcinoma","Abstract":"BACKGROUND: Cholangiocarcinoma is the most common primary tumor of the biliary tract although it accounts for only 2 % of all human malignancies. We herein review hilar cholangiocarcinoma including its risk factors, the main classification systems for tumors, current surgical management of the disease, and the role chemotherapy and liver transplantation may play in selected patients. METHODS: We performed a comprehensive literature search using PubMed, Medline, and the Cochrane library for the period 1980-2015 using the following MeSH terms: \"hilar cholangiocarcinoma\", \"biliary cancer\", and \"cholangiocarcinoma\". Only recent studies that were published in English and in peer reviewed journals were included. FINDINGS: Hilar cholangiocarcinoma is a disease of advanced age with an unclear etiology, most frequently found in Southeast Asia and relatively rare in Western countries. The best chance of long-term survival and potential cure is surgical resection with negative surgical margins, but many patients are unresectable due to locally advanced or metastatic disease at diagnosis. As a result of recent efforts, new methods of management have been identified for these patients, including preoperative portal vein embolism and biliary drainage, neoadjuvant chemotherapy with subsequent transplantation, and chemoradiation therapy. CONCLUSION: Current management of hilar cholangiocarcinoma depends on extent of the tumor at presentation and includes surgical resection, liver transplantation, portal vein embolization, and chemoradiation therapy. Our understanding of hilar cholangiocarcinoma has improved in recent years and further research offers hope to improve the outcome in patients with these rare tumors.","Source":"PubMed","category":"HUMAN","training_data":"Perioperative Management of Hilar Cholangiocarcinoma BACKGROUND: Cholangiocarcinoma is the most common primary tumor of the biliary tract although it accounts for only 2 % of all human malignancies. We herein review hilar cholangiocarcinoma including its risk factors, the main classification systems for tumors, current surgical management of the disease, and the role chemotherapy and liver transplantation may play in selected patients. METHODS: We performed a comprehensive literature search using PubMed, Medline, and the Cochrane library for the period 1980-2015 using the following MeSH terms: \"hilar cholangiocarcinoma\", \"biliary cancer\", and \"cholangiocarcinoma\". Only recent studies that were published in English and in peer reviewed journals were included. FINDINGS: Hilar cholangiocarcinoma is a disease of advanced age with an unclear etiology, most frequently found in Southeast Asia and relatively rare in Western countries. The best chance of long-term survival and potential cure is surgical resection with negative surgical margins, but many patients are unresectable due to locally advanced or metastatic disease at diagnosis. As a result of recent efforts, new methods of management have been identified for these patients, including preoperative portal vein embolism and biliary drainage, neoadjuvant chemotherapy with subsequent transplantation, and chemoradiation therapy. CONCLUSION: Current management of hilar cholangiocarcinoma depends on extent of the tumor at presentation and includes surgical resection, liver transplantation, portal vein embolization, and chemoradiation therapy. Our understanding of hilar cholangiocarcinoma has improved in recent years and further research offers hope to improve the outcome in patients with these rare tumors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"direct targeting suz12 rock2 mir 200b c inhibits cholangiocarcinoma tumourigenesis metastasis background multidrug resistance distant metastasis cholangiocarcinoma result high postoperative recurrence low long term survival rates demonstrated ectopic expression mir 200 suppresses multidrug resistance metastasis cancer however expression function mir 200 cholangiocarcinoma yet described methods study identified dysregulated micrornas mirnas mir cholangiocarcinoma tissue microarray analysis subsequent real time pcr northern blot analyses validated expression candidate mir performed functional analyses investigated relationship mir 200b c expression properties cholangiocarcinoma cells dual luciferase assay applied examine effect mirnas 3 utr target genes demonstrated function target gene sirna transfection identifying downstream pathway via western blotting results found significantly downregulated expression four mir 200 family members mir 200a b c 429 confirmed ectopic mir 200b 200c inhibits migration invasion cholangiocarcinoma cells vitro vivo found mir 200b c influenced tumourigenesis cholangiocarcinoma cells including tumour initiating capacity sphere formation drug resistance found mir 200b c regulated migration invasion capacities directly targeting rho kinase 2 regulated tumorigenic properties directly targeting suz12 subunit polycomb repressor complex conclusion study shows mir 200b c critical role regulation tumorigenic metastatic capacity cholangiocarcinoma reveals probable underlying mechanisms stn","probabilities":0.7966102,"Title":"Direct Targeting Of Suz12/Rock2 By Mir-200B/C Inhibits Cholangiocarcinoma Tumourigenesis And Metastasis","Abstract":"Background: The multidrug resistance and distant metastasis of cholangiocarcinoma result in high postoperative recurrence and low long-term survival rates. It has been demonstrated that the ectopic expression of miR-200 suppresses the multidrug resistance and metastasis of cancer. However, the expression and function of miR-200 in cholangiocarcinoma has not yet been described. \r\n\r\n Methods: In this study, we identified dysregulated microRNAs (miRNAs, miR) in cholangiocarcinoma tissue by microarray analysis, and subsequent real-time PCR and northern blot analyses validated the expression of candidate miR. We performed functional analyses and investigated the relationship between miR-200b/c expression and the properties of cholangiocarcinoma cells. A dual luciferase assay was applied to examine the effect of miRNAs on the 3'-UTR of target genes, and we demonstrated the function of the target gene by siRNA transfection identifying the downstream pathway via western blotting. \r\n\r\n Results: We found significantly downregulated expression of four miR-200 family members (miR-200a/b/c/429) and then confirmed that ectopic miR-200b/200c inhibits the migration and invasion of cholangiocarcinoma cells both in vitro and in vivo. We found that miR-200b/c influenced the tumourigenesis of cholangiocarcinoma cells including their tumour-initiating capacity, sphere formation, and drug resistance. We further found that miR-200b/c regulated migration and invasion capacities by directly targeting rho-kinase 2 and regulated tumorigenic properties by directly targeting SUZ12 (a subunit of a polycomb repressor complex). \r\n\r\n Conclusion: Our study shows that miR-200b/c has a critical role in the regulation of the tumorigenic and metastatic capacity of cholangiocarcinoma and reveals the probable underlying mechanisms.","Source":"STN","category":"ANIMAL","training_data":"Direct Targeting Of Suz12/Rock2 By Mir-200B/C Inhibits Cholangiocarcinoma Tumourigenesis And Metastasis Background: The multidrug resistance and distant metastasis of cholangiocarcinoma result in high postoperative recurrence and low long-term survival rates. It has been demonstrated that the ectopic expression of miR-200 suppresses the multidrug resistance and metastasis of cancer. However, the expression and function of miR-200 in cholangiocarcinoma has not yet been described. \r\n\r\n Methods: In this study, we identified dysregulated microRNAs (miRNAs, miR) in cholangiocarcinoma tissue by microarray analysis, and subsequent real-time PCR and northern blot analyses validated the expression of candidate miR. We performed functional analyses and investigated the relationship between miR-200b/c expression and the properties of cholangiocarcinoma cells. A dual luciferase assay was applied to examine the effect of miRNAs on the 3'-UTR of target genes, and we demonstrated the function of the target gene by siRNA transfection identifying the downstream pathway via western blotting. \r\n\r\n Results: We found significantly downregulated expression of four miR-200 family members (miR-200a/b/c/429) and then confirmed that ectopic miR-200b/200c inhibits the migration and invasion of cholangiocarcinoma cells both in vitro and in vivo. We found that miR-200b/c influenced the tumourigenesis of cholangiocarcinoma cells including their tumour-initiating capacity, sphere formation, and drug resistance. We further found that miR-200b/c regulated migration and invasion capacities by directly targeting rho-kinase 2 and regulated tumorigenic properties by directly targeting SUZ12 (a subunit of a polycomb repressor complex). \r\n\r\n Conclusion: Our study shows that miR-200b/c has a critical role in the regulation of the tumorigenic and metastatic capacity of cholangiocarcinoma and reveals the probable underlying mechanisms. STN","prediction_labels":"HUMAN"},{"cleaned":"curcumin molecular targets obesity obesity related cancers obesity characterized increased bmi associated increased risk several common cancers including colorectal breast endometrial renal esophageal gallbladder melanoma multiple myeloma leukemia lymphoma prostate cancer increased risk obesity related cancers mediated insulin resistance adipokines obesity related inflammatory cytokines sex hormones transcription factors oxidative stress disrupt balance cell proliferation apoptosis yellowish compound curcumin diferuloylmethane known possess multifaceted pharmacological effects molecular mechanisms linking obesity cancer risk curcumin mediates anticancer obesity activities yet publicized curcumin modulates multiple molecular targets reverses insulin resistance well symptoms associated obesity related cancers study show ample evidence exists support recommendations curcumin mediates multiple molecular pathways considered therapeutic value treatment prevention obesity related cancers pubmed","probabilities":0.962963,"Title":"Curcumin molecular targets in obesity and obesity-related cancers","Abstract":"Obesity is characterized as an increased BMI, which is associated with the increased risk of several common cancers, including colorectal, breast, endometrial, renal, esophageal, gallbladder, melanoma, multiple myeloma, leukemia, lymphoma and prostate cancer. The increased risk of obesity-related cancers could be mediated by insulin resistance, adipokines, obesity-related inflammatory cytokines, sex hormones, transcription factors and oxidative stress, which disrupt the balance between cell proliferation and apoptosis. The yellowish compound, curcumin (diferuloylmethane), is known to possess multifaceted pharmacological effects. The molecular mechanisms linking obesity to cancer risk, and how curcumin mediates anticancer and obesity activities, have not yet been publicized. Curcumin modulates multiple molecular targets and reverses insulin resistance as well as other symptoms that are associated with obesity-related cancers. In this study, we show that ample evidence exists to support recommendations that curcumin mediates multiple molecular pathways, and is considered to be of therapeutic value in the treatment and prevention of obesity-related cancers.","Source":"PubMed","category":"HUMAN","training_data":"Curcumin molecular targets in obesity and obesity-related cancers Obesity is characterized as an increased BMI, which is associated with the increased risk of several common cancers, including colorectal, breast, endometrial, renal, esophageal, gallbladder, melanoma, multiple myeloma, leukemia, lymphoma and prostate cancer. The increased risk of obesity-related cancers could be mediated by insulin resistance, adipokines, obesity-related inflammatory cytokines, sex hormones, transcription factors and oxidative stress, which disrupt the balance between cell proliferation and apoptosis. The yellowish compound, curcumin (diferuloylmethane), is known to possess multifaceted pharmacological effects. The molecular mechanisms linking obesity to cancer risk, and how curcumin mediates anticancer and obesity activities, have not yet been publicized. Curcumin modulates multiple molecular targets and reverses insulin resistance as well as other symptoms that are associated with obesity-related cancers. In this study, we show that ample evidence exists to support recommendations that curcumin mediates multiple molecular pathways, and is considered to be of therapeutic value in the treatment and prevention of obesity-related cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma anatomical location dependent clinical prognostic genetic disparities background anatomical location considered diagnostic therapeutic approaches cholangiocarcinoma cca however disparities extents proportion surgical candidates prognostic factors prognostic genetic networks susceptibility lymph node dissection disease stage diagnosis remain confirmed methods total 11 710 patients cholangiocarcinoma surveillance epidemiology end results cancer registries seer 45 cca patients paired tumor normal specimens cancer genome atlas studied kaplan meier estimation cox proportional hazards regression pearson correlation comparison anatomical location distal intrahepatic perihilar dependent ccas differential expressive gene stratification potential interactive gene identification confirmation pathways prognostic networks carried results survival outcomes favorable distal type followed perihilar intrahepatic types postsurgical prognosis slightly higher intrahepatic type compared perihilar type distant historic stage diagnosis noticed intrahepatic type significant prognostic factors hazards ratios dependent anatomical location addition lymph node dissection provided significant survival benefits perihilar type furthermore prognosis predictive genes well potential processes pathways significantly among anatomical location dependent types genes barely overlapped conclusions disparities almost aspects among distal intrahepatic perihilar ccas anatomical location needs considered treatment prognostic estimation identifying targets developing therapeutic approaches cca stn","probabilities":0.9799733,"Title":"Cholangiocarcinoma: Anatomical Location-Dependent Clinical Prognostic And Genetic Disparities","Abstract":"Background: Anatomical location is considered in diagnostic and therapeutic approaches of cholangiocarcinoma (CCA). However, disparities and its extents in proportion of surgical candidates, prognostic factors, prognostic genetic networks, susceptibility for lymph node dissection, and disease stage at diagnosis remain to be confirmed. \n\n Methods: A total of 11,710 patients with cholangiocarcinoma from Surveillance, Epidemiology, and End Results Cancer Registries (SEER) and 45 CCA patients with paired tumor and normal specimens from The Cancer Genome Atlas were studied. Kaplan-Meier estimation, Cox proportional hazards regression, Pearson's correlation, comparison between anatomical location (distal, intrahepatic, and perihilar)-dependent CCAs, differential expressive gene stratification, potential interactive gene identification, and confirmation on pathways of the prognostic networks were carried out. \n\n Results: Survival outcomes were most favorable in the distal type, followed by perihilar and intrahepatic types, but postsurgical prognosis was slightly higher in intrahepatic type compared to perihilar type. Distant historic stage at diagnosis was noticed in intrahepatic type. Significant prognostic factors and their hazards ratios were dependent to the anatomical location. In addition, lymph node dissection provided significant survival benefits in perihilar type only. Furthermore, prognosis-predictive genes, as well as potential processes and pathways, were significantly among the anatomical location-dependent types that the genes barely overlapped. \n\n Conclusions: There are disparities in almost all aspects among distal, intrahepatic, and perihilar CCAs. Anatomical location needs to be considered in treatment, prognostic estimation, identifying targets, and developing therapeutic approaches for CCA.","Source":"STN","category":"HUMAN","training_data":"Cholangiocarcinoma: Anatomical Location-Dependent Clinical Prognostic And Genetic Disparities Background: Anatomical location is considered in diagnostic and therapeutic approaches of cholangiocarcinoma (CCA). However, disparities and its extents in proportion of surgical candidates, prognostic factors, prognostic genetic networks, susceptibility for lymph node dissection, and disease stage at diagnosis remain to be confirmed. \n\n Methods: A total of 11,710 patients with cholangiocarcinoma from Surveillance, Epidemiology, and End Results Cancer Registries (SEER) and 45 CCA patients with paired tumor and normal specimens from The Cancer Genome Atlas were studied. Kaplan-Meier estimation, Cox proportional hazards regression, Pearson's correlation, comparison between anatomical location (distal, intrahepatic, and perihilar)-dependent CCAs, differential expressive gene stratification, potential interactive gene identification, and confirmation on pathways of the prognostic networks were carried out. \n\n Results: Survival outcomes were most favorable in the distal type, followed by perihilar and intrahepatic types, but postsurgical prognosis was slightly higher in intrahepatic type compared to perihilar type. Distant historic stage at diagnosis was noticed in intrahepatic type. Significant prognostic factors and their hazards ratios were dependent to the anatomical location. In addition, lymph node dissection provided significant survival benefits in perihilar type only. Furthermore, prognosis-predictive genes, as well as potential processes and pathways, were significantly among the anatomical location-dependent types that the genes barely overlapped. \n\n Conclusions: There are disparities in almost all aspects among distal, intrahepatic, and perihilar CCAs. Anatomical location needs to be considered in treatment, prognostic estimation, identifying targets, and developing therapeutic approaches for CCA. STN","prediction_labels":"HUMAN"},{"cleaned":"hepatic artery resection bismuth type iii iv hilar cholangiocarcinoma reconstruction always required objective objective study examine feasibility hepatic artery resection har without subsequent reconstruction rcs specified patients bismuth type iii iv hilar cholangiocarcinoma methods retrospectively reviewed 63 patients underwent hepatic artery resection bismuth type iii iv hilar cholangiocarcinoma patients subsequently enrolled two groups based whether artery reconstruction conducted postoperative morbidity mortality long term survival outcome compared two groups results 29 patients har group 34 patients har rcs group patients hepatic artery reconstruction tended longer operative time 545 6 143 1 min vs 656 3 192 8 min p 0 013 smaller tumor size 3 0 1 1 cm vs 2 5 0 9 cm p 0 036 r0 resection margin comparable har group har rcs group 86 2 vs 85 3 p 0 05 twelve patients 41 4 24 complications har group 13 patients 38 2 25 complications har rcs group recorded p 0 799 postoperative hepatic failure rate 13 8 vs 5 9 postoperative mortality rate 3 4 vs 2 9 also comparable two groups har group overall 1 3 5 year survival rates 72 41 19 respectively har rcs group overall 1 3 5 year survival rates 79 45 25 respectively p 0 928 conclusions hepatic artery resection without reconstruction also safe feasible surgical procedure highly selected cases bismuth type iii iv hilar cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Hepatic Artery Resection for Bismuth Type III and IV Hilar Cholangiocarcinoma: Is Reconstruction Always Required?","Abstract":"OBJECTIVE: The objective of the study is to examine the feasibility of hepatic artery resection (HAR) without subsequent reconstruction (RCS) in specified patients of Bismuth type III and IV hilar cholangiocarcinoma. METHODS: We retrospectively reviewed 63 patients who underwent hepatic artery resection for Bismuth type III and IV hilar cholangiocarcinoma. These patients were subsequently enrolled into two groups based on whether the artery reconstruction was conducted. Postoperative morbidity and mortality, and long-term survival outcome were compared between the two groups. RESULTS: There were 29 patients in HAR group and 34 patients in the HAR + RCS group. Patients with hepatic artery reconstruction tended to have longer operative time (545.6 ± 143.1 min vs. 656.3 ± 192.8 min; P = 0.013) and smaller tumor size (3.0 ± 1.1 cm vs. 2.5 ± 0.9 cm; P = 0.036). The R0 resection margin was comparable between the HAR group and HAR + RCS group (86.2 vs. 85.3%; P > 0.05). Twelve patients (41.4%) with 24 complications in HAR group and 13 patients (38.2%) with 25 complications in HAR + RCS group were recorded (P = 0.799). The postoperative hepatic failure rate (13.8 vs. 5.9%) and postoperative mortality rate (3.4% vs. 2.9%) were also comparable between the two groups. In the HAR group, the overall 1-, 3-, and 5-year survival rates were 72, 41, and 19%, respectively; while in the HAR + RCS group, the overall 1-, 3-, and 5-year survival rates were 79, 45, and 25%, respectively (P = 0.928). CONCLUSIONS: Hepatic artery resection without reconstruction is also a safe and feasible surgical procedure for highly selected cases of Bismuth type III and IV hilar cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Hepatic Artery Resection for Bismuth Type III and IV Hilar Cholangiocarcinoma: Is Reconstruction Always Required? OBJECTIVE: The objective of the study is to examine the feasibility of hepatic artery resection (HAR) without subsequent reconstruction (RCS) in specified patients of Bismuth type III and IV hilar cholangiocarcinoma. METHODS: We retrospectively reviewed 63 patients who underwent hepatic artery resection for Bismuth type III and IV hilar cholangiocarcinoma. These patients were subsequently enrolled into two groups based on whether the artery reconstruction was conducted. Postoperative morbidity and mortality, and long-term survival outcome were compared between the two groups. RESULTS: There were 29 patients in HAR group and 34 patients in the HAR + RCS group. Patients with hepatic artery reconstruction tended to have longer operative time (545.6 ± 143.1 min vs. 656.3 ± 192.8 min; P = 0.013) and smaller tumor size (3.0 ± 1.1 cm vs. 2.5 ± 0.9 cm; P = 0.036). The R0 resection margin was comparable between the HAR group and HAR + RCS group (86.2 vs. 85.3%; P > 0.05). Twelve patients (41.4%) with 24 complications in HAR group and 13 patients (38.2%) with 25 complications in HAR + RCS group were recorded (P = 0.799). The postoperative hepatic failure rate (13.8 vs. 5.9%) and postoperative mortality rate (3.4% vs. 2.9%) were also comparable between the two groups. In the HAR group, the overall 1-, 3-, and 5-year survival rates were 72, 41, and 19%, respectively; while in the HAR + RCS group, the overall 1-, 3-, and 5-year survival rates were 79, 45, and 25%, respectively (P = 0.928). CONCLUSIONS: Hepatic artery resection without reconstruction is also a safe and feasible surgical procedure for highly selected cases of Bismuth type III and IV hilar cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"lymph node metastases patients undergoing surgery gallbladder cancer extension lymph node dissection prognostic value lymph node ratio background lymph node ln status one strongest prognostic factors gallbladder cancer gbc resection adequate extension ln dissection stratification prognosis n patients debated present study aims clarify issues methods total 112 consecutive patients underwent operations gbc ln dissection analyzed twenty five patients 22 3 d1 dissection hepatic pedicle 87 77 7 d2 dissection hepatic pedicle celiac retro pancreatic area ln ratio lnr computed follows number metastatic lns number retrieved lns results median number retrieved lns 7 1 35 fifty nine patients 52 7 ln metastases 22 n2 d2 dissection allowed retrieval lns 8 vs 3 p 0 0007 similar short term outcomes common bile duct cbd resection n 41 increase number retrieved lns five patients d2 dissection identified skip ln metastases otherwise missed ln metastases negatively impacted survival 5 years survival 57 2 n0 vs 12 4 n p 0 0001 n1 n2 patients similar survival rates number ln 1 3 vs 4 impact prognosis lnr 0 15 stratified prognosis n patients 5 years survival 32 7 lnr 0 15 vs 10 3 lnr 0 15 multivariate analysis p 0 007 conclusions d2 ln dissection recommended patients allows better staging cbd resection improve ln dissection lnr 0 15 site metastatic lns stratified prognoses n patients pubmed","probabilities":0.9799733,"Title":"Lymph node metastases in patients undergoing surgery for a gallbladder cancer Extension of the lymph node dissection and prognostic value of the lymph node ratio","Abstract":"BACKGROUND: Lymph node (LN) status is one of the strongest prognostic factors after gallbladder cancer (GBC) resection. The adequate extension of LN dissection and the stratification of the prognosis in N+ patients have been debated. The present study aims to clarify these issues. METHODS: A total of 112 consecutive patients who underwent operations for GBC with LN dissection were analyzed. Twenty-five patients (22.3%) had D1 dissection (hepatic pedicle), and 87 (77.7%) had D2 dissection (hepatic pedicle, celiac and retro-pancreatic area). The LN ratio (LNR) was computed as follows: number of metastatic LNs/number of retrieved LNs. RESULTS: The median number of retrieved LNs was 7 (1-35). Fifty-nine patients (52.7%) had LN metastases (22 N2). D2 dissection allowed the retrieval of more LNs (8 vs. 3, p = 0.0007), with similar short-term outcomes. Common bile duct (CBD) resection (n = 41) did not increase the number of retrieved LNs. In five patients, D2 dissection identified skip LN metastases that otherwise would have been missed. LN metastases negatively impacted survival (5-years survival 57.2% if N0 vs. 12.4% if N+, p < 0.0001), but N1 and N2 patients had similar survival rates. The number of LN+ (1-3 vs. ≥4) did not impact prognosis. An LNR = 0.15 stratified the prognosis of N+ patients: 5-years survival 32.7% if LNR ≤ 0.15 vs. 10.3% if LNR > 0.15 (multivariate analysis p = 0.007). CONCLUSIONS: A D2 LN dissection is recommended in all patients, because it allows for better staging. CBD resection does not improve LN dissection. An LNR = 0.15, not the site of metastatic LNs, stratified the prognoses of N+ patients.","Source":"PubMed","category":"HUMAN","training_data":"Lymph node metastases in patients undergoing surgery for a gallbladder cancer Extension of the lymph node dissection and prognostic value of the lymph node ratio BACKGROUND: Lymph node (LN) status is one of the strongest prognostic factors after gallbladder cancer (GBC) resection. The adequate extension of LN dissection and the stratification of the prognosis in N+ patients have been debated. The present study aims to clarify these issues. METHODS: A total of 112 consecutive patients who underwent operations for GBC with LN dissection were analyzed. Twenty-five patients (22.3%) had D1 dissection (hepatic pedicle), and 87 (77.7%) had D2 dissection (hepatic pedicle, celiac and retro-pancreatic area). The LN ratio (LNR) was computed as follows: number of metastatic LNs/number of retrieved LNs. RESULTS: The median number of retrieved LNs was 7 (1-35). Fifty-nine patients (52.7%) had LN metastases (22 N2). D2 dissection allowed the retrieval of more LNs (8 vs. 3, p = 0.0007), with similar short-term outcomes. Common bile duct (CBD) resection (n = 41) did not increase the number of retrieved LNs. In five patients, D2 dissection identified skip LN metastases that otherwise would have been missed. LN metastases negatively impacted survival (5-years survival 57.2% if N0 vs. 12.4% if N+, p < 0.0001), but N1 and N2 patients had similar survival rates. The number of LN+ (1-3 vs. ≥4) did not impact prognosis. An LNR = 0.15 stratified the prognosis of N+ patients: 5-years survival 32.7% if LNR ≤ 0.15 vs. 10.3% if LNR > 0.15 (multivariate analysis p = 0.007). CONCLUSIONS: A D2 LN dissection is recommended in all patients, because it allows for better staging. CBD resection does not improve LN dissection. An LNR = 0.15, not the site of metastatic LNs, stratified the prognoses of N+ patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical treatment intrahepatic cholangiocarcinoma europe single center experience intrahepatic cholangiocarcinoma second common primary liver tumor aim study analyze retrospectively outcome surgical treatment prognostic factors clinical histopathological treatment data 221 patients treated 1995 2010 institution investigated univariate multivariate analysis patient data performed patients r0 r1 resection presented overall survival 67 54 5 1 year 40 36 4 3 years respectively survival patients without resection tumor dismal 26 3 4 1 3 years respectively survival resection statistically different cases r0 versus r1 resection p 0 639 log rank univariate cox regression revealed higher stages significant hazard survival p 0 048 hazard ratio hr 1 211 95 confidence interval ci 1 002 2 465 patients tumor recurrence significantly inferior long term survival compared patients without recurrence p 0 001 log rank presence lymph node metastasis n1 independent prognostic factor survival resection risk adjusted multivariate cox regression p 0 001 hr 2 577 95 ci 1 742 3 813 adjuvant chemotherapy improve patient survival significantly p 0 550 log rank surgical resection still best treatment option intrahepatic cholangiocarcinoma regarding patient long term survival r0 r1 resection enable better survival rates compared surgical exploration without resection status n status tumor recurrence seem important prognostic factors resection pubmed","probabilities":0.9799733,"Title":"Surgical treatment for intrahepatic cholangiocarcinoma in Europe: a single center experience","Abstract":"Intrahepatic cholangiocarcinoma is the second most common primary liver tumor. The aim of this study was to analyze retrospectively the outcome of surgical treatment and prognostic factors. Clinical, histopathological and treatment data of 221 patients treated from 1995 to 2010 at our institution were investigated. Univariate and multivariate analysis of the patient's data was performed. Patients after R0 and R1 resection presented an overall survival of 67% and 54.5% after 1 year and 40% and 36.4% after 3 years, respectively. The survival of patients without resection of the tumor was dismal with 26% and 3.4% after 1 and 3 years, respectively. Survival after resection was not statistically different in cases with R0 versus R1 resection (P = 0.639, log rank). Univariate Cox regression revealed that higher T stages are a significant hazard for survival (P = 0.048, hazard ratio (HR): 1.211, 95% confidence interval (CI): 1.002-2.465). Patients with tumor recurrence had a significantly inferior long-term survival when compared to patients without recurrence (P < 0.001, log rank). Presence of lymph node metastasis (N1) was an independent prognostic factor for survival after resection in risk-adjusted multivariate Cox regression (P < 0.001, HR: 2.577, 95% CI: 1.742-3.813). Adjuvant chemotherapy did not improve patient survival significantly (P = 0.550, log rank). Surgical resection is still the best treatment option for intrahepatic cholangiocarcinoma regarding the patient's long-term survival. R0 and R1 resection enable both better survival rates when compared to surgical exploration without resection. T status, N status, and tumor recurrence seem to be the most important prognostic factors after resection.","Source":"PubMed","category":"HUMAN","training_data":"Surgical treatment for intrahepatic cholangiocarcinoma in Europe: a single center experience Intrahepatic cholangiocarcinoma is the second most common primary liver tumor. The aim of this study was to analyze retrospectively the outcome of surgical treatment and prognostic factors. Clinical, histopathological and treatment data of 221 patients treated from 1995 to 2010 at our institution were investigated. Univariate and multivariate analysis of the patient's data was performed. Patients after R0 and R1 resection presented an overall survival of 67% and 54.5% after 1 year and 40% and 36.4% after 3 years, respectively. The survival of patients without resection of the tumor was dismal with 26% and 3.4% after 1 and 3 years, respectively. Survival after resection was not statistically different in cases with R0 versus R1 resection (P = 0.639, log rank). Univariate Cox regression revealed that higher T stages are a significant hazard for survival (P = 0.048, hazard ratio (HR): 1.211, 95% confidence interval (CI): 1.002-2.465). Patients with tumor recurrence had a significantly inferior long-term survival when compared to patients without recurrence (P < 0.001, log rank). Presence of lymph node metastasis (N1) was an independent prognostic factor for survival after resection in risk-adjusted multivariate Cox regression (P < 0.001, HR: 2.577, 95% CI: 1.742-3.813). Adjuvant chemotherapy did not improve patient survival significantly (P = 0.550, log rank). Surgical resection is still the best treatment option for intrahepatic cholangiocarcinoma regarding the patient's long-term survival. R0 and R1 resection enable both better survival rates when compared to surgical exploration without resection. T status, N status, and tumor recurrence seem to be the most important prognostic factors after resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cytotoxic activity thai medicinal plants human cholangiocarcinoma laryngeal hepatocarcinoma cells vitro background cholangiocarcinoma serious public health thailand increasing incidence mortality rates present study aimed investigate cytotoxic activities crude ethanol extracts total 28 plants 5 recipes used thai folklore medicine human cholangiocarcinoma cl 6 human laryngeal hep 2 human hepatocarcinoma hepg2 cell lines vitro methods cytotoxic activity plant extracts cancerous cell lines compared normal cell line renal epithelial cell hre assessed using mtt assay 5 fluorouracil used positive control ic50 concentration inhibits cell growth 50 selectivity index si calculated results extracts seven plant species atractylodes lancea kaempferia galangal zingiber officinal piper chaba mesua ferrea ligusticum sinense mimusops elengi one folklore recipe pra sa prao yhai exhibited promising activity cholangiocarcinoma cl 6 cell line survival less 50 concentration 50 g ml among extracts five plants one recipe atractylodes lancea kaempferia galangal zingiber officinal piper chaba mesua ferrea pra sa prao yhai recipe showed potent cytotoxic activity mean ic50 values 24 09 37 36 34 26 40 74 48 23 44 12 g ml respectively possessed high activity hep 2 cell mean ic50 ranging 18 93 32 40 g ml contrast activity hepatoma cell hepg2 varied markedly mean ic50 ranged 9 67 115 47 g ml promising extract zingiber officinal ic50 9 67 g ml sensitivity four cells 5 fu also varied according cell types particularly cl 6 cell ic50 757 micromolar extract atractylodes lancea appears potent selective cholangiocarcinoma ic50 24 09 g ml si 8 6 conclusions ethanolic extracts five plants one folklore recipe showed potent cytotoxic activity cl 6 cell sensitivity cancerous cell lines varied according cell types hepatocarcinoma cell line hepg2 appears resistant tested extracts stn","probabilities":1.0,"Title":"Cytotoxic Activity Of Thai Medicinal Plants Against Human Cholangiocarcinoma Laryngeal And Hepatocarcinoma Cells In Vitro","Abstract":"Background: Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro. \r\n\r\n Methods: Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC50 (concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated. \r\n\r\n Results: The extracts from seven plant species (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, Ligusticum sinense, Mimusops elengi) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, and Pra-Sa-Prao-Yhai recipe) showed potent cytotoxic activity with mean IC50 values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC50 ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC50 ranged from 9.67 to 115.47 μg/ml. The only promising extract was from Zingiber officinal (IC50=9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC50=757 micromolar). The extract from Atractylodes lancea appears to be both the most potent and most selective against cholangiocarcinoma (IC50=24.09 μg/ml, SI = 8.6). \r\n\r\n Conclusions: The ethanolic extracts from five plants and one folklore recipe showed potent cytotoxic activity against CL-6 cell. Sensitivity to other cancerous cell lines varied according to cell types and the hepatocarcinoma cell line. HepG2 appears to be the most resistant to the tested extracts.","Source":"STN","category":"ANIMAL","training_data":"Cytotoxic Activity Of Thai Medicinal Plants Against Human Cholangiocarcinoma Laryngeal And Hepatocarcinoma Cells In Vitro Background: Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro. \r\n\r\n Methods: Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC50 (concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated. \r\n\r\n Results: The extracts from seven plant species (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, Ligusticum sinense, Mimusops elengi) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, and Pra-Sa-Prao-Yhai recipe) showed potent cytotoxic activity with mean IC50 values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC50 ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC50 ranged from 9.67 to 115.47 μg/ml. The only promising extract was from Zingiber officinal (IC50=9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC50=757 micromolar). The extract from Atractylodes lancea appears to be both the most potent and most selective against cholangiocarcinoma (IC50=24.09 μg/ml, SI = 8.6). \r\n\r\n Conclusions: The ethanolic extracts from five plants and one folklore recipe showed potent cytotoxic activity against CL-6 cell. Sensitivity to other cancerous cell lines varied according to cell types and the hepatocarcinoma cell line. HepG2 appears to be the most resistant to the tested extracts. STN","prediction_labels":"ANIMAL"},{"cleaned":"curative resection hilar cholangiocarcinoma single center experience long term follow nan pubmed","probabilities":0.9799733,"Title":"Curative Resection for Hilar Cholangiocarcinoma: Single-Center Experience with Long-Term Follow-Up","Abstract":"NaN","Source":"PubMed","category":"HUMAN","training_data":"Curative Resection for Hilar Cholangiocarcinoma: Single-Center Experience with Long-Term Follow-Up nan PubMed","prediction_labels":"HUMAN"},{"cleaned":"next generation sequencing survey biliary tract cancer reveals association tumor somatic variants chemotherapy resistance background biliary tract cancers btcs uncommon associated dismal prognosis combinations gemcitabine platinum chemotherapy gemcitabine platinum based therapy gp form standard approach treating advanced btc characterize spectrum mutations identify potential biomarkers gp response btc study evaluated genomic landscape assessed whether mutations affecting dna repair associated gp resistance methods pretreatment formalin fixed paraffin embedded samples 183 btc patients treated gp analyzed cox regression models used determine association mutations progression free survival pfs overall survival os results genes incidence 10 considered individual gene independently predictive gp response patients unresectable btc received gp first line therapy joint status cyclin dependent kinase inhibitor 2a cdkn2a tumor protein 53 tp53 rich interaction domain 1a arid1a associated pfs p 0004 os p 0001 patients mutations cdkn2a tp53 identified poor prognosis cohort median pfs 2 63 months median os 5 22 months patients mutant arid1a regardless single mutation status tp53 cdkn2a similar outcomes patient exhibited mutations 3 genes median pfs 20 37 months os reached conclusions largest exploratory analysis kind btc 3 prevalent mutually exclusive mutations represent distinct patient cohorts mutations prognostic may represent predictive biomarker gp response prospective studies validate findings needed include incorporation therapies exploit genomic instability observed mutations btc cancer 2016 122 3657 66 2016 american cancer society pubmed","probabilities":0.9799733,"Title":"Next-generation sequencing survey of biliary tract cancer reveals the association between tumor somatic variants and chemotherapy resistance","Abstract":"BACKGROUND: Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance. METHODS: Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS). RESULTS: When genes with an incidence > 10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P = .0004) and OS (P ≤ .0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached. CONCLUSIONS: In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. © 2016 American Cancer Society.","Source":"PubMed","category":"HUMAN","training_data":"Next-generation sequencing survey of biliary tract cancer reveals the association between tumor somatic variants and chemotherapy resistance BACKGROUND: Biliary tract cancers (BTCs) are uncommon and are associated with a dismal prognosis. Combinations of gemcitabine and platinum chemotherapy (gemcitabine and platinum-based therapy [GP]) form the standard approach for treating advanced BTC. To characterize the spectrum of mutations and to identify potential biomarkers for a GP response in BTC, this study evaluated the genomic landscape and assessed whether mutations affecting DNA repair were associated with GP resistance. METHODS: Pretreatment, formalin-fixed, paraffin-embedded samples from 183 BTC patients treated with GP were analyzed. Cox regression models were used to determine the association between mutations, progression-free survival (PFS), and overall survival (OS). RESULTS: When genes with an incidence > 10% were considered, no individual gene was independently predictive of a GP response. In patients with unresectable BTC who received GP as their first-line therapy, the joint status of cyclin-dependent kinase inhibitor 2A (CDKN2A), tumor protein 53 (TP53), and AT-rich interaction domain 1A (ARID1A) was associated with PFS (P = .0004) and OS (P ≤ .0001). Patients with mutations in CDKN2A and TP53 were identified as a poor-prognosis cohort with a median PFS of 2.63 months and a median OS of 5.22 months. Patients with mutant ARID1A, regardless of the single-mutation status of TP53 or CDKN2A, had similar outcomes. A patient who exhibited mutations in all 3 genes had a median PFS of 20.37 months, and OS was not reached. CONCLUSIONS: In the largest exploratory analysis of this kind for BTC, 3 prevalent, mutually exclusive mutations represent distinct patient cohorts. These mutations are prognostic and may represent a predictive biomarker for a GP response. Prospective studies to validate these findings are needed, and they should include the incorporation of therapies that exploit the genomic instability observed with these mutations in BTC. Cancer 2016;122:3657-66. © 2016 American Cancer Society. PubMed","prediction_labels":"HUMAN"},{"cleaned":"two week combination chemotherapy gemcitabine high dose folinic acid 5 fluorouracil gemfufol first line treatment metastatic biliary tract cancers background aim study evaluate efficacy tolerability gemcitabine 5 fluorouracil leucovorin gemfufol chemotherapy regimen first line treatment metastatic biliary tract cancer materials methods patients received folinic acid 400 mg m 2 day 1 5 fluorouracil bolus 400 mg m2 day 1 iv infusion 5 fluorouracil 2400 mg m 2 46 hours gemcitabine 1250 mg m 2 day 1 results total 29 patients metastatic biliary tract cancer received gemfufol regimen first line treatment mean follow 22 1 months 95 ci 12 5 31 8 one patient 3 4 achieved complete response 5 17 2 partial response 4 13 8 stable disease median progression free survival 3 3 months 95 ci 2 9 3 7 median overall survival 8 8 months 95 ci 3 5 14 1 year 2 year survival rates 58 6 30 respectively grade 3 4 toxicity included neutropenia 4 patients 13 7 thrombocytopenia 2 6 8 anemia 2 6 8 alopecia 1 3 4 two patients 6 8 developed febrile neutropenia dose reduction achieved 8 patients 27 6 5 patients extended interval dosage 17 2 toxicity conclusions gemfufol chemotherapy regimen generally efficacious tolerable first line treatment metastatic biliary tract cancer pubmed","probabilities":0.9799733,"Title":"Two-week combination chemotherapy with gemcitabine, high-dose folinic acid and 5 fluorouracil (GEMFUFOL) as first-line treatment of metastatic biliary tract cancers","Abstract":"BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer. MATERIALS AND METHODS: All patients received folinic acid 400 mg/m(2) on day 1, 5-fluorouracil bolus 400 mg/ m2 on day 1, IV infusion of 5-fluorouracil 2400 mg/m(2) over 46 hours, and gemcitabine 1250 mg/m(2) on day 1. RESULTS: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the first- line treatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved complete response, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survival was 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1-year and 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in 4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia in 2 (6.8%), and alopecia in 1 (3.4%). Two patients (6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patients had extended-interval dosage (17.2%) for toxicity. CONCLUSIONS: The GEMFUFOL chemotherapy regimen was generally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer.","Source":"PubMed","category":"HUMAN","training_data":"Two-week combination chemotherapy with gemcitabine, high-dose folinic acid and 5 fluorouracil (GEMFUFOL) as first-line treatment of metastatic biliary tract cancers BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of a gemcitabine, 5-fluorouracil and leucovorin (GEMFUFOL) chemotherapy regimen as first line treatment of metastatic biliary tract cancer. MATERIALS AND METHODS: All patients received folinic acid 400 mg/m(2) on day 1, 5-fluorouracil bolus 400 mg/ m2 on day 1, IV infusion of 5-fluorouracil 2400 mg/m(2) over 46 hours, and gemcitabine 1250 mg/m(2) on day 1. RESULTS: A total of 29 patients with metastatic biliary tract cancer received GEMFUFOL regimen as the first- line treatment. The mean follow-up was 22.1 months (95%CI, 12.5-31.8). One patient (3.4%) achieved complete response, 5 (17.2%) had partial response, and 4 (13.8%) had stable disease. The median progression-free survival was 3.3 months (95%CI, 2.9-3.7), and the median overall survival was 8.8 months (95%CI, 3.5-14). The 1-year and 2-year survival rates were 58.6% and 30%, respectively. Grade 3 and 4 toxicity included neutropenia in 4 patients (13.7%), thrombocytopenia in 2 (6.8%), anemia in 2 (6.8%), and alopecia in 1 (3.4%). Two patients (6.8%) developed febrile neutropenia. A dose reduction was achieved in 8 patients (27.6%) while 5 patients had extended-interval dosage (17.2%) for toxicity. CONCLUSIONS: The GEMFUFOL chemotherapy regimen was generally efficacious and tolerable as a first-line treatment of metastatic biliary tract cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"regulated microrna 33b inhibits epithelial mesenchymal transition gallbladder cancer regulating crocc gallbladder cancer gbc relatively rare fatal gastrointestinal tumor microrna 33b mir 33b member mir 33 family reported function tumor suppressor various cancers notably mir 33 predicted target crocc based microarray based analysis hereby aimed characterize effect mir 33b epithelial mesenchymal transition emt gbc potential mechanism involved regulation crocc gbc cell lines mir 33b expressed low levels crocc expressed high levels enhanced emt process examine specific mechanism mir 33b crocc gbc gbc cells treated mir 33b mimic inhibitor sirna crocc assess expression alteration emt related genes cell proliferation migration invasion mir 33b verified target regulate expression crocc mir 33b regulation crocc silencing observed increase level e cadherin decrease levels n cadherin vimentin corresponding impeded cell proliferation migration invasion emt tumor growth findings suggest mir 33b regulation hinders gbc development regulating crocc achieved inhibition emt present study may provide insight novel target gbc treatment stn","probabilities":0.9467213,"Title":"Up-Regulated Microrna-33B Inhibits Epithelial-Mesenchymal Transition In Gallbladder Cancer Through Down-Regulating Crocc","Abstract":"Gallbladder cancer (GBC) is a relatively rare but fatal gastrointestinal tumor. The microRNA-33b (miR-33b), a member of miR-33 family, is reported to function as a tumor suppressor in various cancers. Notably, miR-33 was predicted to target CROCC based on microarray-based analysis. Hereby, we aimed to characterize the effect of miR-33b on epithelial-mesenchymal transition (EMT) in GBC and the potential mechanism involved with the regulation of CROCC. In GBC cell lines, miR-33b expressed at low levels, and CROCC expressed at high levels, with enhanced EMT process. To further examine the specific mechanism of miR-33b and CROCC in GBC, the GBC cells were treated with the miR-33b mimic/inhibitor or siRNA-CROCC to assess the expression alteration of EMT-related genes and cell proliferation, migration, and invasion. MiR-33b was verified to target and down-regulate the expression of CROCC. The miR-33b up-regulation or CROCC silencing was observed to increase the level of E-cadherin but decrease the levels of N-cadherin and Vimentin, corresponding to impeded cell proliferation, migration, invasion, EMT, and tumor growth. The findings suggest that miR-33b up-regulation hinders GBC development through down-regulating CROCC, which was achieved by inhibition of EMT. The present study may provide an insight on a novel target for GBC treatment.","Source":"STN","category":"ANIMAL","training_data":"Up-Regulated Microrna-33B Inhibits Epithelial-Mesenchymal Transition In Gallbladder Cancer Through Down-Regulating Crocc Gallbladder cancer (GBC) is a relatively rare but fatal gastrointestinal tumor. The microRNA-33b (miR-33b), a member of miR-33 family, is reported to function as a tumor suppressor in various cancers. Notably, miR-33 was predicted to target CROCC based on microarray-based analysis. Hereby, we aimed to characterize the effect of miR-33b on epithelial-mesenchymal transition (EMT) in GBC and the potential mechanism involved with the regulation of CROCC. In GBC cell lines, miR-33b expressed at low levels, and CROCC expressed at high levels, with enhanced EMT process. To further examine the specific mechanism of miR-33b and CROCC in GBC, the GBC cells were treated with the miR-33b mimic/inhibitor or siRNA-CROCC to assess the expression alteration of EMT-related genes and cell proliferation, migration, and invasion. MiR-33b was verified to target and down-regulate the expression of CROCC. The miR-33b up-regulation or CROCC silencing was observed to increase the level of E-cadherin but decrease the levels of N-cadherin and Vimentin, corresponding to impeded cell proliferation, migration, invasion, EMT, and tumor growth. The findings suggest that miR-33b up-regulation hinders GBC development through down-regulating CROCC, which was achieved by inhibition of EMT. The present study may provide an insight on a novel target for GBC treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"incidence mixed hepatocellular cholangiocarcinoma pure cholangiocarcinoma explant pathology following liver transplant presumed hepatocellular carcinoma introduction liver transplantation accepted treatment hepatocellular carcinoma contraindications include evidence macrovascular invasion imaging biopsy consistent tumors explants ultimately demonstrate tumor type appreciated preoperatively examined rate ndings outcomes patients methods retrospectively examined series 142 patients analyzed di erences demographic survival explant characteristics data analyzed tests chi square results 59 total transplants performed presumed hcc explant pathology 7 59 explants either mixed hcc cholangiocarcinoma pure cholangiocarcinoma found evidence explant pathology demonstrating either mixed type tumor cholangiocarcinoma associated decreased survival 1 year 58 patients alive versus 96 hcc group also noted cause death patients mixed type tumors cholangiocarcinoma died due disease recurrence two patients survive 1 year hcc group died due causes liver disease disease recurrence di erence noted age bmi cause liver failure total number tumors greatest tumor size evidence lymphovascular invasion explant size conclusion diagnosis mixed type tumor cholangiocarcinoma negative prognostic indicator survival e orts made identify patients able preoperatively avoid excess morbidity mortality google scholar","probabilities":0.9799733,"Title":"Incidence Of Mixed Hepatocellular-Cholangiocarcinoma Or Pure Cholangiocarcinoma On Explant Pathology Following Liver Transplant For Presumed Hepatocellular Carcinoma","Abstract":"Introduction: Liver transplantation is an accepted treatment for hepatocellular \ncarcinoma. Contraindications include evidence of macrovascular invasion or imaging \nor biopsy consistent with other tumors. Some explants ultimately demonstrate a \ntumor type not appreciated preoperatively. We examined our rate of these  ndings \nand outcomes in these patients. Methods: We retrospectively examined a series of \n142 patients. We analyzed for di erences in demographic, survival, and explant \ncharacteristics. Data were analyzed with t-tests or Chi Square. Results: 59 of the \ntotal transplants were performed for presumed HCC. On explant pathology, 7 of the \n59 explants had either mixed HCC/cholangiocarcinoma or pure cholangiocarcinoma. \nWe found evidence that explant pathology demonstrating either mixed type tumor \nor cholangiocarcinoma was associated with decreased survival at 1 year (58% of \npatients alive versus 96% in the HCC group). We also noted that the cause of death \nin all patients with mixed type tumors or cholangiocarcinoma died due to disease \nrecurrence. The two patients who did not survive to 1 year in the HCC group died \ndue to causes other than liver disease or disease recurrence. No di erence was \nnoted in age, BMI, cause of liver failure, total number of tumors, greatest tumor \nsize, evidence of lymphovascular invasion or explant size Conclusion: Diagnosis \nof mixed type tumor or cholangiocarcinoma is a negative prognostic indicator for \nsurvival. E orts should be made to identify these patients as able preoperatively to \navoid excess morbidity and mortality","Source":"Google Scholar","category":"ANIMAL","training_data":"Incidence Of Mixed Hepatocellular-Cholangiocarcinoma Or Pure Cholangiocarcinoma On Explant Pathology Following Liver Transplant For Presumed Hepatocellular Carcinoma Introduction: Liver transplantation is an accepted treatment for hepatocellular \ncarcinoma. Contraindications include evidence of macrovascular invasion or imaging \nor biopsy consistent with other tumors. Some explants ultimately demonstrate a \ntumor type not appreciated preoperatively. We examined our rate of these  ndings \nand outcomes in these patients. Methods: We retrospectively examined a series of \n142 patients. We analyzed for di erences in demographic, survival, and explant \ncharacteristics. Data were analyzed with t-tests or Chi Square. Results: 59 of the \ntotal transplants were performed for presumed HCC. On explant pathology, 7 of the \n59 explants had either mixed HCC/cholangiocarcinoma or pure cholangiocarcinoma. \nWe found evidence that explant pathology demonstrating either mixed type tumor \nor cholangiocarcinoma was associated with decreased survival at 1 year (58% of \npatients alive versus 96% in the HCC group). We also noted that the cause of death \nin all patients with mixed type tumors or cholangiocarcinoma died due to disease \nrecurrence. The two patients who did not survive to 1 year in the HCC group died \ndue to causes other than liver disease or disease recurrence. No di erence was \nnoted in age, BMI, cause of liver failure, total number of tumors, greatest tumor \nsize, evidence of lymphovascular invasion or explant size Conclusion: Diagnosis \nof mixed type tumor or cholangiocarcinoma is a negative prognostic indicator for \nsurvival. E orts should be made to identify these patients as able preoperatively to \navoid excess morbidity and mortality Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"surgical outcomes prognostic factors ampulla vater cancer background aims prognosis patients ampulla vater cancer better periampullary cancers aim present study determine clinicopathologic factors predictive survival recurrence patients ampulla vater cancer material methods 1991 2008 identified reviewed 78 patients ampulla vater cancer retrospectively clinicopathologic factors possibly influencing survival recurrence statistically analyzed results pancreaticoduodenectomy performed 68 patients 2 patients underwent transduodenal ampullectomy hospital mortality 2 6 5 year survival rates following resection 59 9 univariate analysis overall survival revealed total bilirubin greater 5 mg dl ulcerative tumors differentiation pancreatic invasion significant prognostic factors recurrence occurred 31 patients univariate analysis disease free survival revealed total bilirubin greater 5mg dl preoperative biliary drainage tumor differentiation stage statistically significant multivariate analysis revealed tumor differentiation independent prognostic factor recurrence presence lymph node metastasis affect overall survival significantly study however two metastatic lymph nodes significantly affect disease free survival conclusions pancreaticoduodenectomy safe surgical procedure acceptable long term survival ampulla vater cancer pancreaticoduodenectomy lymph node dissection might control lymph node spread enhance survival outcome pubmed","probabilities":0.9799733,"Title":"Surgical outcomes and prognostic factors for ampulla of Vater cancer","Abstract":"BACKGROUND AND AIMS: The prognosis for patients with ampulla of Vater cancer is better than other periampullary cancers. The aim of the present study is to determine the clinicopathologic factors predictive of survival and recurrence in patients with ampulla of Vater cancer. MATERIAL AND METHODS: From 1991 to 2008, we identified and reviewed 78 patients with ampulla of Vater cancer retrospectively. Clinicopathologic factors possibly influencing survival and recurrence were statistically analyzed. RESULTS: Pancreaticoduodenectomy was performed in 68 patients and 2 patients underwent transduodenal ampullectomy. Hospital mortality was 2.6%. The 5-year survival rates following resection were 59.9%. Univariate analysis for overall survival revealed that total bilirubin greater than 5 mg/dl, ulcerative tumors, differentiation, and pancreatic invasion were significant prognostic factors. Recurrence occurred in 31 patients. Univariate analysis for disease-free survival revealed that total bilirubin greater than 5mg/dl, preoperative biliary drainage, tumor differentiation, and stage were statistically significant. Multivariate analysis revealed that tumor differentiation was an independent prognostic factor for recurrence. The presence of lymph node metastasis did not affect overall survival significantly in this study. However, two or more metastatic lymph nodes significantly affect disease-free survival. CONCLUSIONS: Pancreaticoduodenectomy is a safe surgical procedure with acceptable long-term survival for ampulla of Vater cancer. Pancreaticoduodenectomy with lymph node dissection might control lymph node spread and enhance survival outcome.","Source":"PubMed","category":"HUMAN","training_data":"Surgical outcomes and prognostic factors for ampulla of Vater cancer BACKGROUND AND AIMS: The prognosis for patients with ampulla of Vater cancer is better than other periampullary cancers. The aim of the present study is to determine the clinicopathologic factors predictive of survival and recurrence in patients with ampulla of Vater cancer. MATERIAL AND METHODS: From 1991 to 2008, we identified and reviewed 78 patients with ampulla of Vater cancer retrospectively. Clinicopathologic factors possibly influencing survival and recurrence were statistically analyzed. RESULTS: Pancreaticoduodenectomy was performed in 68 patients and 2 patients underwent transduodenal ampullectomy. Hospital mortality was 2.6%. The 5-year survival rates following resection were 59.9%. Univariate analysis for overall survival revealed that total bilirubin greater than 5 mg/dl, ulcerative tumors, differentiation, and pancreatic invasion were significant prognostic factors. Recurrence occurred in 31 patients. Univariate analysis for disease-free survival revealed that total bilirubin greater than 5mg/dl, preoperative biliary drainage, tumor differentiation, and stage were statistically significant. Multivariate analysis revealed that tumor differentiation was an independent prognostic factor for recurrence. The presence of lymph node metastasis did not affect overall survival significantly in this study. However, two or more metastatic lymph nodes significantly affect disease-free survival. CONCLUSIONS: Pancreaticoduodenectomy is a safe surgical procedure with acceptable long-term survival for ampulla of Vater cancer. Pancreaticoduodenectomy with lymph node dissection might control lymph node spread and enhance survival outcome. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic relevance new 8th edition union international cancer control classification tnm staging ampulla vater carcinoma objective aim study investigate clinical relevance 8th edition union international cancer control classification tnm staging ampulla vater carcinoma ac methods total 104 consecutive patients underwent macroscopic curative resection ac january 2002 september 2017 investigated results significant differences recurrence free survival rfs found t1a t1b p 0 0030 t1b t2 p 0 9319 t2 t3a p 0 0732 t3a t3b p 0 2118 prognostic impact depth duodenal invasion pancreatic invasion define category evaluated regard duodenal invasion significant differences rfs found negative submucosa classifications p 0 0012 muscularis propria serosa classifications p 0 0131 submucosa muscularis propria classifications p 0 6390 regard pancreatic invasion significant differences rfs found negative 0 5 cm classifications p 0 0001 0 5 cm 0 5 cm classifications p 0 0062 cox proportional hazard analysis rfs revealed duodenal invasion submucosa muscularis propria negative hazard ratio hr 5 08 serosa negative hr 7 42 pancreatic invasion 0 5 cm negative hr 8 23 0 5 cm negative hr 9 81 independent prognostic factors alternative new category proposed based hrs follows t1 tumor limited ampulla vater sphincter oddi t2 duodenal invasion submucosa muscularis propria t3 pancreatic invasion 0 5 cm duodenal invasion serosa t4 pancreatic invasion 0 5 cm alternative category well classify subgroup prognostic differences conclusions reconsideration category based prognostic impact tnm factors including depth duodenal pancreatic invasion required 8th edition category pubmed","probabilities":0.9799733,"Title":"The Prognostic Relevance of the New 8th Edition of the Union for International Cancer Control Classification of TNM Staging for Ampulla of Vater Carcinoma","Abstract":"OBJECTIVE: The aim of this study was to investigate the clinical relevance of the 8th edition of the Union for International Cancer Control classification of TNM staging for ampulla of Vater carcinoma (AC). METHODS: A total of 104 consecutive patients who underwent macroscopic curative resection for AC between January 2002 and September 2017 were investigated. RESULTS: Significant differences in recurrence-free survival (RFS) were found between T1a and T1b (p = 0.0030), but not between T1b and T2 (p = 0.9319), T2 and T3a (p = 0.0732), or T3a and T3b (p = 0.2118). The prognostic impact of the depth of duodenal invasion and pancreatic invasion, which define the T category, were evaluated. With regard to duodenal invasion, significant differences in RFS were found between the negative and submucosa classifications (p = 0.0012) and the muscularis propria and serosa classifications (p = 0.0131), but not between the submucosa and muscularis propria classifications (p = 0.6390). With regard to pancreatic invasion, significant differences in RFS were found between the negative and ≤ 0.5 cm classifications (p = 0.0001), and ≤ 0.5 cm and > 0.5 cm classifications (p = 0.0062). A Cox proportional hazard analysis for RFS revealed that duodenal invasion (submucosa or muscularis propria/negative, hazard ratio [HR] 5.08; serosa/negative, HR 7.42), and pancreatic invasion (≤ 0.5 cm/negative, HR 8.23; > 0.5 cm/negative, HR 9.81) were independent prognostic factors. An alternative new T category was proposed, based on the HRs, as follows: T1, tumor limited to the ampulla of Vater or sphincter of Oddi; T2, duodenal invasion (submucosa or muscularis propria); T3, pancreatic invasion (≤ 0.5 cm) or duodenal invasion (serosa); and T4, pancreatic invasion (> 0.5 cm). This alternative T category can well classify each subgroup with prognostic differences. CONCLUSIONS: Reconsideration of the T category based on the prognostic impact of TNM factors, including the depth of duodenal and pancreatic invasion, are required in the 8th edition T category.","Source":"PubMed","category":"HUMAN","training_data":"The Prognostic Relevance of the New 8th Edition of the Union for International Cancer Control Classification of TNM Staging for Ampulla of Vater Carcinoma OBJECTIVE: The aim of this study was to investigate the clinical relevance of the 8th edition of the Union for International Cancer Control classification of TNM staging for ampulla of Vater carcinoma (AC). METHODS: A total of 104 consecutive patients who underwent macroscopic curative resection for AC between January 2002 and September 2017 were investigated. RESULTS: Significant differences in recurrence-free survival (RFS) were found between T1a and T1b (p = 0.0030), but not between T1b and T2 (p = 0.9319), T2 and T3a (p = 0.0732), or T3a and T3b (p = 0.2118). The prognostic impact of the depth of duodenal invasion and pancreatic invasion, which define the T category, were evaluated. With regard to duodenal invasion, significant differences in RFS were found between the negative and submucosa classifications (p = 0.0012) and the muscularis propria and serosa classifications (p = 0.0131), but not between the submucosa and muscularis propria classifications (p = 0.6390). With regard to pancreatic invasion, significant differences in RFS were found between the negative and ≤ 0.5 cm classifications (p = 0.0001), and ≤ 0.5 cm and > 0.5 cm classifications (p = 0.0062). A Cox proportional hazard analysis for RFS revealed that duodenal invasion (submucosa or muscularis propria/negative, hazard ratio [HR] 5.08; serosa/negative, HR 7.42), and pancreatic invasion (≤ 0.5 cm/negative, HR 8.23; > 0.5 cm/negative, HR 9.81) were independent prognostic factors. An alternative new T category was proposed, based on the HRs, as follows: T1, tumor limited to the ampulla of Vater or sphincter of Oddi; T2, duodenal invasion (submucosa or muscularis propria); T3, pancreatic invasion (≤ 0.5 cm) or duodenal invasion (serosa); and T4, pancreatic invasion (> 0.5 cm). This alternative T category can well classify each subgroup with prognostic differences. CONCLUSIONS: Reconsideration of the T category based on the prognostic impact of TNM factors, including the depth of duodenal and pancreatic invasion, are required in the 8th edition T category. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence rates survival gallbladder cancer usa gallbladder cancer rare malignancy countries racial sociodemographic factors associated incidence survival poorly defined aimed investigate population based gallbladder cancer incidence survival trends basis clinical characteristics sociodemographic factors usa gallbladder cancer incidence survival data 2001 2012 obtained 18 registries surveillance epidemiology end results database incidence rates joinpoint trends calculated demographic subgroup survival trends assessed using cox proportional hazard models total 7769 patients identified overall gallbladder cancer incidence rates significantly change 2001 2012 period incidence rates three times higher hispanics 1 6 times higher blacks compared whites time period incidence rates significantly increased among blacks decreased among hispanics male sex hazard ratio hr 1 10 95 confidence interval ci 1 03 1 17 older age hr 1 73 95 ci 1 53 1 96 single divorced statuses hr 1 19 95 ci 1 09 1 30 1 12 95 ci 1 01 1 24 independently associated shorter overall survival whereas higher education hr 0 89 95 ci 0 82 0 97 higher income hr 0 89 95 ci 0 82 0 96 associated longer survival furthermore overall survival improved races ethnicities except hispanics blacks overall incidence rates gallbladder cancer stable 2001 2012 hispanics highest incidence rates incidence rates blacks rise stn","probabilities":0.9799733,"Title":"The Incidence Rates And Survival Of Gallbladder Cancer In The Usa","Abstract":"Gallbladder cancer is a rare malignancy in most countries. The racial and sociodemographic factors associated with its incidence and survival are poorly defined. We aimed to investigate population-based gallbladder cancer incidence and survival trends on the basis of clinical characteristics and sociodemographic factors in the USA. Gallbladder cancer incidence and survival data from 2001 to 2012 were obtained from 18 registries of the Surveillance, Epidemiology, and End Results database. Incidence rates and Joinpoint trends were calculated by demographic subgroup. Survival trends were assessed using Cox proportional hazard models. A total of 7769 patients were identified. The overall gallbladder cancer incidence rates did not significantly change during the 2001-2012 period. Incidence rates were three times higher in Hispanics and 1.6 times higher in Blacks compared with Whites. Over the time period, incidence rates significantly increased among Blacks and decreased among Hispanics. Male sex [hazard ratio (HR): 1.10, 95% confidence interval (CI): 1.03-1.17], older age (HR: 1.73, 95% CI: 1.53-1.96), and single and divorced statuses (HR: 1.19, 95% CI: 1.09-1.30 and 1.12, 95% CI: 1.01-1.24) were independently associated with shorter overall survival, whereas higher education (HR: 0.89, 95% CI: 0.82-0.97) and higher income (HR: 0.89, 95% CI: 0.82-0.96) were associated with longer survival. Furthermore, overall survival has improved in all races/ethnicities except for Hispanics and Blacks. The overall incidence rates for gallbladder cancer were stable during 2001-2012. Hispanics have the highest incidence rates, but the incidence rates in Blacks are on the rise.","Source":"STN","category":"HUMAN","training_data":"The Incidence Rates And Survival Of Gallbladder Cancer In The Usa Gallbladder cancer is a rare malignancy in most countries. The racial and sociodemographic factors associated with its incidence and survival are poorly defined. We aimed to investigate population-based gallbladder cancer incidence and survival trends on the basis of clinical characteristics and sociodemographic factors in the USA. Gallbladder cancer incidence and survival data from 2001 to 2012 were obtained from 18 registries of the Surveillance, Epidemiology, and End Results database. Incidence rates and Joinpoint trends were calculated by demographic subgroup. Survival trends were assessed using Cox proportional hazard models. A total of 7769 patients were identified. The overall gallbladder cancer incidence rates did not significantly change during the 2001-2012 period. Incidence rates were three times higher in Hispanics and 1.6 times higher in Blacks compared with Whites. Over the time period, incidence rates significantly increased among Blacks and decreased among Hispanics. Male sex [hazard ratio (HR): 1.10, 95% confidence interval (CI): 1.03-1.17], older age (HR: 1.73, 95% CI: 1.53-1.96), and single and divorced statuses (HR: 1.19, 95% CI: 1.09-1.30 and 1.12, 95% CI: 1.01-1.24) were independently associated with shorter overall survival, whereas higher education (HR: 0.89, 95% CI: 0.82-0.97) and higher income (HR: 0.89, 95% CI: 0.82-0.96) were associated with longer survival. Furthermore, overall survival has improved in all races/ethnicities except for Hispanics and Blacks. The overall incidence rates for gallbladder cancer were stable during 2001-2012. Hispanics have the highest incidence rates, but the incidence rates in Blacks are on the rise. STN","prediction_labels":"HUMAN"},{"cleaned":"tumor infiltrating inflammatory immune cells prognostic indicator survival patients extrahepatic cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Tumor-Infiltrating Inflammatory And Immune Cells As Prognostic Indicator For Survival In Patients With Extrahepatic Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Tumor-Infiltrating Inflammatory And Immune Cells As Prognostic Indicator For Survival In Patients With Extrahepatic Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"increased ephb2 expression predicts cholangiocarcinoma metastasis activation ephrin eph receptors largest tyrosine kinase families cell surface receptor recently addressed human cholangiocarcinoma cca therefore present study aimed investigate role eph receptors ligands cca 50 cases human cca tested immunohistochemical staining demonstrated ephb2 ephb4 ephrinb1 ephrinb2 100 positive cca tissues overexpressions proteins 56 56 70 48 cases respectively high expression ephb2 significantly correlated metastatic status patients p 0 027 also found high co expression level ephb2 ephrinb1 ephb2 ephrinb2 significantly correlated metastatic status patients p 0 034 p 0 024 furthermore showed high co expression level ephb4 mvd ephrinb1 mvd significantly correlated metastasis status cca patients p 0 012 p 0 029 demonstrated ephb2 suppression using sirna significantly reduced cca cell migration decreasing phosphorylation focal adhesion kinase fak paxillin conclusion upregulation ephb2 receptors specific ligands ephrinb1 ephrinb2 leads cca metastasis suppression ephb2 expression well inhibition downstream signaling proteins might serve possible therapeutic strategies human cca stn","probabilities":0.9467213,"Title":"Increased Ephb2 Expression Predicts Cholangiocarcinoma Metastasis","Abstract":"The activation of Ephrin (Eph) receptors, the largest tyrosine kinase families of cell surface receptor, has recently been addressed in human cholangiocarcinoma (CCA). Therefore, the present study aimed to investigate the role of Eph receptors and its ligands in CCA. Of all 50 cases of human CCA tested, immunohistochemical staining demonstrated that EphB2, EphB4, ephrinB1, and ephrinB2 were 100 % positive in CCA tissues with overexpressions of the above proteins as 56, 56, 70, and 48 % of cases, respectively. High expression of EphB2 was significantly correlated with the metastatic status of patients (P = 0.027). We also found that the high co-expression level of EphB2/ephrinB1 or EphB2/ephrinB2 were significantly correlated with the metastatic status of the patients (P = 0.034 and P = 0.024). Furthermore, we showed that the high co-expression level of EphB4/MVD and ephrinB1/MVD were significantly correlated with the metastasis status of CCA patients (P = 0.012 and P = 0.029). We further demonstrated that the EphB2 suppression using siRNA significantly reduced CCA cell migration by decreasing the phosphorylation of focal adhesion kinase (FAK) and paxillin. In conclusion, the upregulation of EphB2 receptors and its specific ligands (ephrinB1 and ephrinB2) leads to CCA metastasis. Suppression of EphB2 expression as well as inhibition of its downstream signaling proteins might serve as possible therapeutic strategies in human CCA.","Source":"STN","category":"ANIMAL","training_data":"Increased Ephb2 Expression Predicts Cholangiocarcinoma Metastasis The activation of Ephrin (Eph) receptors, the largest tyrosine kinase families of cell surface receptor, has recently been addressed in human cholangiocarcinoma (CCA). Therefore, the present study aimed to investigate the role of Eph receptors and its ligands in CCA. Of all 50 cases of human CCA tested, immunohistochemical staining demonstrated that EphB2, EphB4, ephrinB1, and ephrinB2 were 100 % positive in CCA tissues with overexpressions of the above proteins as 56, 56, 70, and 48 % of cases, respectively. High expression of EphB2 was significantly correlated with the metastatic status of patients (P = 0.027). We also found that the high co-expression level of EphB2/ephrinB1 or EphB2/ephrinB2 were significantly correlated with the metastatic status of the patients (P = 0.034 and P = 0.024). Furthermore, we showed that the high co-expression level of EphB4/MVD and ephrinB1/MVD were significantly correlated with the metastasis status of CCA patients (P = 0.012 and P = 0.029). We further demonstrated that the EphB2 suppression using siRNA significantly reduced CCA cell migration by decreasing the phosphorylation of focal adhesion kinase (FAK) and paxillin. In conclusion, the upregulation of EphB2 receptors and its specific ligands (ephrinB1 and ephrinB2) leads to CCA metastasis. Suppression of EphB2 expression as well as inhibition of its downstream signaling proteins might serve as possible therapeutic strategies in human CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"long term risk cancer following ileal pouch anal anastomosis ulcerative colitis background overall risk cancer following ileal pouch anal anastomosis ipaa unknown pouch cancer surveillance controversial evaluated long term risk cancer national cohort patients ulcerative colitis ipaa emphasis pouch cancer methods data incident cancers extracted national danish cancer registry incidence rates site specific cancers compared patients ipaa gender age matched comparison cohort background population obtain incidence rate ratios irrs results total 1723 patients ipaa operated ulcerative colitis period 1980 2010 matched 8615 individuals background population median follow 12 9 years interquartile range iqr 7 7 19 6 years two pouch cancers 0 12 found 16 27 years respectively population comparison cohort 38 intestinal cancers 0 45 found 35 colorectal risk hepatobiliary cancer higher patients ipaa irr 13 0 95 confidence interval ci 3 1 76 1 half affected patients coexisting primary sclerosing cholangitis risk cancer overall following ipaa identical comparison cohort irr 1 05 0 84 1 31 conclusions pouch cancer following ipaa rare questioning need general rather selective surveillance overall cancer risk comparable background population increased risk hepatobiliary cancer likely effect coexisting liver disease causally related ipaa google scholar","probabilities":0.9799733,"Title":"Long-Term Risk Of Cancer Following Ileal Pouch-Anal Anastomosis For Ulcerative Colitis","Abstract":"Background\nThe overall risk of cancer following ileal pouch-anal anastomosis [IPAA] is unknown, and pouch cancer surveillance is controversial. We evaluated long-term risk of cancer in a national cohort of patients with ulcerative colitis and IPAA, with emphasis on pouch cancer.\nMethods\nData on incident cancers were extracted from the national Danish Cancer Registry. Incidence rates for all site-specific cancers were compared between patients with IPAA and a gender- and age-matched comparison cohort from the background population to obtain incidence rate ratios [IRRs].\nResults\nA total of 1723 patients with IPAA, operated for ulcerative colitis in the period 1980–2010, were matched to 8615 individuals from the background population. During a median follow-up of 12.9 years (interquartile range [IQR] 7.7–19.6 years), two pouch cancers [0.12%] were found after 16 and 27 years, respectively. In the population comparison cohort, 38 intestinal cancers [0.45%] were found, of which 35 were colorectal. The risk of hepatobiliary cancer was higher for patients with IPAA {IRR = 13.0 (95% confidence interval [CI]: 3.1–76.1)}, and half of the affected patients had coexisting primary sclerosing cholangitis. The risk of cancer overall following IPAA was identical to that of the comparison cohort: IRR = 1.05 [0.84–1.31].\nConclusions\nPouch cancer following IPAA is very rare, questioning the need for general, rather than selective, surveillance. The overall cancer risk is comparable to that of the background population, and the increased risk of hepatobiliary cancer is likely an effect of coexisting liver disease and not causally related to IPAA.","Source":"Google Scholar","category":"HUMAN","training_data":"Long-Term Risk Of Cancer Following Ileal Pouch-Anal Anastomosis For Ulcerative Colitis Background\nThe overall risk of cancer following ileal pouch-anal anastomosis [IPAA] is unknown, and pouch cancer surveillance is controversial. We evaluated long-term risk of cancer in a national cohort of patients with ulcerative colitis and IPAA, with emphasis on pouch cancer.\nMethods\nData on incident cancers were extracted from the national Danish Cancer Registry. Incidence rates for all site-specific cancers were compared between patients with IPAA and a gender- and age-matched comparison cohort from the background population to obtain incidence rate ratios [IRRs].\nResults\nA total of 1723 patients with IPAA, operated for ulcerative colitis in the period 1980–2010, were matched to 8615 individuals from the background population. During a median follow-up of 12.9 years (interquartile range [IQR] 7.7–19.6 years), two pouch cancers [0.12%] were found after 16 and 27 years, respectively. In the population comparison cohort, 38 intestinal cancers [0.45%] were found, of which 35 were colorectal. The risk of hepatobiliary cancer was higher for patients with IPAA {IRR = 13.0 (95% confidence interval [CI]: 3.1–76.1)}, and half of the affected patients had coexisting primary sclerosing cholangitis. The risk of cancer overall following IPAA was identical to that of the comparison cohort: IRR = 1.05 [0.84–1.31].\nConclusions\nPouch cancer following IPAA is very rare, questioning the need for general, rather than selective, surveillance. The overall cancer risk is comparable to that of the background population, and the increased risk of hepatobiliary cancer is likely an effect of coexisting liver disease and not causally related to IPAA. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cd90 expression human intrahepatic cholangiocarcinoma associated lymph node metastasis poor prognosis background objectives intrahepatic cholangiocarcinoma icc second common primary liver cancer however prognosis remains poor expression cluster differentiation 90 cd90 identified indicator poor prognosis many cancers examined importance cd90 expression icc methods performed immunohistological assays cd90 human icc surgical specimens assessed relationship clinicopathological findings prognosis moreover analyzed characteristics cd90 cells mainly respect metastatic potential using human icc cell lines results cd90 expression significantly associated lymph node metastasis revealed independent prognostic factor cd90 cells present icc specimens appear cancer associated fibroblasts express smooth muscle actin vitro cd90 cells exhibited greater migratory ability higher expression epithelial mesenchymal transition emt related genes including cxcr4 mmp7 cd90 cells wnt catenin signaling pathway activation also heightened cd90 cells cells emt appeared induced cxcr4 mmp7 expression activation wnt catenin signaling conclusion cd90 cells demonstrate high metastatic potential owing wnt catenin signaling activation associated poor prognosis icc pubmed","probabilities":0.875,"Title":"CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph node metastasis and poor prognosis","Abstract":"BACKGROUND AND OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. However, its prognosis remains poor. Expression of cluster of differentiation 90 (CD90) has been identified as an indicator of poor prognosis in many cancers. Here, we examined the importance of CD90 expression in ICC. METHODS: We performed immunohistological assays for CD90 in human ICC surgical specimens and assessed its relationship with clinicopathological findings and prognosis. Moreover, we analyzed the characteristics of CD90(+/-) cells, mainly with respect to metastatic potential, using human ICC cell lines. RESULTS: CD90 expression was significantly associated with lymph node metastasis and was revealed to be an independent prognostic factor. The CD90(+) cells present in ICC specimens did not appear to be cancer-associated fibroblasts, as they did not express α-smooth muscle actin. In vitro, CD90 (+) cells exhibited greater migratory ability and higher expression of epithelial-mesenchymal transition (EMT)-related genes, including CXCR4 and MMP7, than CD90(-) cells. Wnt/β-catenin signaling pathway activation was also heightened in CD90(+) cells. In such cells, EMT appeared to be induced by CXCR4 and MMP7 expression through activation of Wnt/β-catenin signaling. CONCLUSION: CD90(+) cells demonstrate high metastatic potential owing to Wnt/β-catenin signaling activation and are associated with poor prognosis in ICC.","Source":"PubMed","category":"ANIMAL","training_data":"CD90 expression in human intrahepatic cholangiocarcinoma is associated with lymph node metastasis and poor prognosis BACKGROUND AND OBJECTIVES: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. However, its prognosis remains poor. Expression of cluster of differentiation 90 (CD90) has been identified as an indicator of poor prognosis in many cancers. Here, we examined the importance of CD90 expression in ICC. METHODS: We performed immunohistological assays for CD90 in human ICC surgical specimens and assessed its relationship with clinicopathological findings and prognosis. Moreover, we analyzed the characteristics of CD90(+/-) cells, mainly with respect to metastatic potential, using human ICC cell lines. RESULTS: CD90 expression was significantly associated with lymph node metastasis and was revealed to be an independent prognostic factor. The CD90(+) cells present in ICC specimens did not appear to be cancer-associated fibroblasts, as they did not express α-smooth muscle actin. In vitro, CD90 (+) cells exhibited greater migratory ability and higher expression of epithelial-mesenchymal transition (EMT)-related genes, including CXCR4 and MMP7, than CD90(-) cells. Wnt/β-catenin signaling pathway activation was also heightened in CD90(+) cells. In such cells, EMT appeared to be induced by CXCR4 and MMP7 expression through activation of Wnt/β-catenin signaling. CONCLUSION: CD90(+) cells demonstrate high metastatic potential owing to Wnt/β-catenin signaling activation and are associated with poor prognosis in ICC. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"c met intrahepatic cholangiocarcinoma high frequency amplification predicts protein expression unique molecular subtype increasing number gene alterations discovered intrahepatic cholangiocarcinoma icc molecular targets promising diagnosis treatment distinct subpopulations carrying unique molecular signatures c met amplification associated variety tumors including icc however characteristics alteration assessed icc determining ratios c met chromosome enumeration probe cep 7 double colour probes evaluated presence c met amplification cohort 133 icc tumors fluorescence situ hybridization fish determined levels met protein expression immunohistochemistry ihc analyzed clinicopathologic records samples 21 15 8 high frequency 41 30 8 low frequency c met genetic amplification 71 53 4 normal c met gene significant differences gross classification p 0 045 microscopic cholangitis p 0 030 mucus level tumors p 0 012 stage p 0 007 three groups combined high frequency low frequency amplifications c met one group microscopic cholangitis p 0 010 stage p 0 016 showed significant differences compared normal c met gene expression however combined low frequency c met amplification group normal c met group compared combined group high frequency c met amplification group high frequency group younger patients p 0 047 non mass forming mf type cases according gross classification p 0 015 secreted mucus p 0 002 appeared higher stage p 0 031 combined group ihc results although cluster c met amplification predicted protein overexpression high frequency amplification associated protein expression genetic statuses p 0 000 low frequency c met amplification exhibited similar biology normal gene regarded high frequency amplification c met unique molecular subtype may play important roles tumor progression may used prognostic marker targeted therapy google scholar","probabilities":0.9799733,"Title":"C-Met In Intrahepatic Cholangiocarcinoma: High-Frequency Amplification Predicts Protein Expression And A Unique Molecular Subtype","Abstract":"As an increasing number of gene alterations have been discovered in intrahepatic cholangiocarcinoma (ICC), molecular targets are promising for the diagnosis and treatment of distinct subpopulations carrying unique molecular signatures. C-MET amplification is associated with a variety of tumors, including ICC; however, the characteristics of this alteration have not been assessed in ICC. By determining the ratios of C-MET/chromosome enumeration probe (CEP) 7 double-colour probes, we evaluated the presence of C-MET amplification in a cohort of 133 ICC tumors by fluorescence in situ hybridization (FISH). We further determined the levels of MET protein expression by immunohistochemistry (IHC) and analyzed clinicopathologic records. Of the samples, 21 (15.8 %) had high-frequency and 41 (30.8 %) had low-frequency C-MET genetic amplification, and 71 (53.4 %) had a normal C-MET gene. There were significant differences in gross classification (p = 0.045), microscopic cholangitis (p = 0.030), mucus level in tumors (p = 0.012) and T stage (p = 0.007) between the three groups. When we combined high-frequency and low-frequency amplifications of C-MET into one group, only microscopic cholangitis (p = 0.010) and stage (p = 0.016) showed significant differences compared to normal C-MET gene expression. However, when we combined the low-frequency C-MET amplification group with the normal C-MET group and compared this combined group with the high-frequency C-MET amplification group, the high-frequency group had more younger patients (p = 0.047), had more non-mass-forming (MF)-type cases according to gross classification (p = 0.015), secreted more mucus (p = 0.002) and appeared to have a higher T stage (p = 0.031) than the combined group. For IHC results, although only cluster C-MET amplification predicted protein overexpression, high-frequency amplification was associated with more protein expression than the other genetic statuses (p = 0.000). As low-frequency C-MET amplification exhibited similar biology to that of the normal gene, we regarded high-frequency amplification of C-MET as a unique molecular subtype. It may play important roles in tumor progression and may be used as a prognostic marker for targeted therapy.","Source":"Google Scholar","category":"HUMAN","training_data":"C-Met In Intrahepatic Cholangiocarcinoma: High-Frequency Amplification Predicts Protein Expression And A Unique Molecular Subtype As an increasing number of gene alterations have been discovered in intrahepatic cholangiocarcinoma (ICC), molecular targets are promising for the diagnosis and treatment of distinct subpopulations carrying unique molecular signatures. C-MET amplification is associated with a variety of tumors, including ICC; however, the characteristics of this alteration have not been assessed in ICC. By determining the ratios of C-MET/chromosome enumeration probe (CEP) 7 double-colour probes, we evaluated the presence of C-MET amplification in a cohort of 133 ICC tumors by fluorescence in situ hybridization (FISH). We further determined the levels of MET protein expression by immunohistochemistry (IHC) and analyzed clinicopathologic records. Of the samples, 21 (15.8 %) had high-frequency and 41 (30.8 %) had low-frequency C-MET genetic amplification, and 71 (53.4 %) had a normal C-MET gene. There were significant differences in gross classification (p = 0.045), microscopic cholangitis (p = 0.030), mucus level in tumors (p = 0.012) and T stage (p = 0.007) between the three groups. When we combined high-frequency and low-frequency amplifications of C-MET into one group, only microscopic cholangitis (p = 0.010) and stage (p = 0.016) showed significant differences compared to normal C-MET gene expression. However, when we combined the low-frequency C-MET amplification group with the normal C-MET group and compared this combined group with the high-frequency C-MET amplification group, the high-frequency group had more younger patients (p = 0.047), had more non-mass-forming (MF)-type cases according to gross classification (p = 0.015), secreted more mucus (p = 0.002) and appeared to have a higher T stage (p = 0.031) than the combined group. For IHC results, although only cluster C-MET amplification predicted protein overexpression, high-frequency amplification was associated with more protein expression than the other genetic statuses (p = 0.000). As low-frequency C-MET amplification exhibited similar biology to that of the normal gene, we regarded high-frequency amplification of C-MET as a unique molecular subtype. It may play important roles in tumor progression and may be used as a prognostic marker for targeted therapy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"circular rna hipk3 promotes gallbladder cancer cell growth sponging microrna 124 recent studies implied circhipk3 abundant circular rna circrna participates tumorigenesis cancer progression expression potential functions human gallbladder cancer examined study show circhipk3 upregulated human gallbladder cancer cells level low gallbladder epithelial cells circhipk3 silencing targeted sirna potently inhibited survival proliferation established primary human gallbladder cancer cells inducing cell apoptosis conversely ectopic expression circhipk3 promote cancer cell proliferation gallbladder cancer cells circhipk3 sponged tumor suppressive microrna 124 mir 124 sequester inhibit activity thereby leading increased expression mir 124 targets including rock1 rho associated protein kinase 1 cdk6 rho associated protein kinase ectopic expression mir 124 b y lentiviral vector mimicked abolished actions circhipk3 sirna gallbladder cancer cells last show circhipk3 upregulated human gallbladder cancer tissues correlated mir 124 downregulation rock1 cdk6 upregulation together conclude circhipk3 promotes gallbladder cancer cell growth possibly sponging mir 124 expressed circhipk3 novel therapeutic target diagnosis marker human gallbladder cancer stn","probabilities":0.9467213,"Title":"Circular Rna Hipk3 Promotes Gallbladder Cancer Cell Growth By Sponging Microrna-124","Abstract":"Recent studies have implied that circHIPK3, an abundant circular RNA (circRNA), participates in tumorigenesis and cancer progression. Its expression and potential functions in human gallbladder cancer were examined in this study. We show that circHIPK3 is upregulated in human gallbladder cancer cells. But its level is low in gallbladder epithelial cells. circHIPK3 silencing by targeted siRNA potently inhibited survival and proliferation of established and primary human gallbladder cancer cells, while inducing cell apoptosis. Conversely, ectopic over-expression of circHIPK3 can further promote cancer cell proliferation. In gallbladder cancer cells, circHIPK3 sponged the tumor-suppressive microRNA-124 (miR-124) to sequester and inhibit its activity, thereby leading to increased expression of miR-124 targets, including ROCK1 (rho-associated protein kinase 1) and CDK6 (rho-associated protein kinase). Ectopic over-expression of miR-124 b y a lentiviral vector mimicked and abolished actions by circHIPK3 siRNA in gallbladder cancer cells. At last, we show that circHIPK3 is upregulated in human gallbladder cancer tissues, which is correlated with miR-124 downregulation and ROCK1-CDK6 upregulation. Together, we conclude that circHIPK3 promotes gallbladder cancer cell growth possibly by sponging miR-124. The over-expressed circHIPK3 could be a novel therapeutic target and diagnosis marker of human gallbladder cancer.","Source":"STN","category":"ANIMAL","training_data":"Circular Rna Hipk3 Promotes Gallbladder Cancer Cell Growth By Sponging Microrna-124 Recent studies have implied that circHIPK3, an abundant circular RNA (circRNA), participates in tumorigenesis and cancer progression. Its expression and potential functions in human gallbladder cancer were examined in this study. We show that circHIPK3 is upregulated in human gallbladder cancer cells. But its level is low in gallbladder epithelial cells. circHIPK3 silencing by targeted siRNA potently inhibited survival and proliferation of established and primary human gallbladder cancer cells, while inducing cell apoptosis. Conversely, ectopic over-expression of circHIPK3 can further promote cancer cell proliferation. In gallbladder cancer cells, circHIPK3 sponged the tumor-suppressive microRNA-124 (miR-124) to sequester and inhibit its activity, thereby leading to increased expression of miR-124 targets, including ROCK1 (rho-associated protein kinase 1) and CDK6 (rho-associated protein kinase). Ectopic over-expression of miR-124 b y a lentiviral vector mimicked and abolished actions by circHIPK3 siRNA in gallbladder cancer cells. At last, we show that circHIPK3 is upregulated in human gallbladder cancer tissues, which is correlated with miR-124 downregulation and ROCK1-CDK6 upregulation. Together, we conclude that circHIPK3 promotes gallbladder cancer cell growth possibly by sponging miR-124. The over-expressed circHIPK3 could be a novel therapeutic target and diagnosis marker of human gallbladder cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic significance tie2 expressing monocytes hilar cholangiocarcinoma background objectives angiopoietins angs play pivotal role angiogenesis inflammation associated prognosis malignancies monocyte express ang receptor tie2 correlate prognosis cancer aimed investigate prognostic value angs tie2 expressing monocytes tems cholangiocarcinoma methods analyzed surgically resected tumor specimens hilar cholangiocarcinoma n 47 distribution angs ang 1 ang 2 tems defined co expression cd14 ang receptor tie2 ang expression abundance tems correlated clinicopathologic characteristics tumor recurrence patients survival results high ang 1 expression correlated reduced metastasis p 0 05 patients characterized invading ang receptor bearing tems tumor showed lower tumor recurrence p 0 05 furthermore tems tumor tumor invasive front correlated increased survival p 0 05 tems tumor invasive front confirmed independent prognosticator multivariate survival analysis p 0 05 conclusions high ang 1 expression hilar cholangiocarcinoma infiltration tems defines subgroup patients beneficial tumor characteristics prolonged survival besides suggested functional links ang expression recruitment tems data possible clinical implications novel diagnostic tools j surg oncol 2016 114 91 98 2016 wiley periodicals inc pubmed","probabilities":0.9799733,"Title":"Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma","Abstract":"BACKGROUND AND OBJECTIVES: Angiopoietins (Angs) play a pivotal role in angiogenesis and inflammation, and are associated with prognosis in malignancies. Monocyte express Ang-receptor TIE2 and correlate with prognosis in cancer. We aimed to investigate the prognostic value of Angs and TIE2-expressing monocytes (TEMs) in cholangiocarcinoma. METHODS: We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution of Angs (Ang 1/Ang 2) and TEMs, as defined by co-expression of CD14 and Ang receptor TIE2. Ang expression and abundance of TEMs were correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. RESULTS: High Ang 1 expression correlated with reduced metastasis (P < 0.05). Patients characterized by invading Ang-receptor bearing TEMs in tumor showed lower tumor recurrence (P < 0.05). Furthermore, TEMs in tumor and tumor invasive front correlated with increased survival (P < 0.05). TEMs in tumor invasive front were confirmed as independent prognosticator in multivariate survival analysis (P < 0.05). CONCLUSIONS: High Ang 1 expression in hilar cholangiocarcinoma and infiltration of TEMs defines a subgroup of patients with beneficial tumor characteristics and prolonged survival. Besides suggested functional links between Ang expression and recruitment of TEMs, our data have possible clinical implications as novel diagnostic tools. J. Surg. Oncol. 2016;114:91-98. © 2016 Wiley Periodicals, Inc.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of TIE2-expressing monocytes in hilar cholangiocarcinoma BACKGROUND AND OBJECTIVES: Angiopoietins (Angs) play a pivotal role in angiogenesis and inflammation, and are associated with prognosis in malignancies. Monocyte express Ang-receptor TIE2 and correlate with prognosis in cancer. We aimed to investigate the prognostic value of Angs and TIE2-expressing monocytes (TEMs) in cholangiocarcinoma. METHODS: We analyzed surgically resected tumor specimens of hilar cholangiocarcinoma (n = 47) for distribution of Angs (Ang 1/Ang 2) and TEMs, as defined by co-expression of CD14 and Ang receptor TIE2. Ang expression and abundance of TEMs were correlated with clinicopathologic characteristics, tumor recurrence and patients' survival. RESULTS: High Ang 1 expression correlated with reduced metastasis (P < 0.05). Patients characterized by invading Ang-receptor bearing TEMs in tumor showed lower tumor recurrence (P < 0.05). Furthermore, TEMs in tumor and tumor invasive front correlated with increased survival (P < 0.05). TEMs in tumor invasive front were confirmed as independent prognosticator in multivariate survival analysis (P < 0.05). CONCLUSIONS: High Ang 1 expression in hilar cholangiocarcinoma and infiltration of TEMs defines a subgroup of patients with beneficial tumor characteristics and prolonged survival. Besides suggested functional links between Ang expression and recruitment of TEMs, our data have possible clinical implications as novel diagnostic tools. J. Surg. Oncol. 2016;114:91-98. © 2016 Wiley Periodicals, Inc. PubMed","prediction_labels":"HUMAN"},{"cleaned":"characterization cholangiocarcinomas clinical topographic features growing oncological reality introduction cholangiocarcinomas account 3 malignant gastrointestinal neoplasms incidence intra hepatic cholangiocarcinomas increased unknown reasons 1 2 aims methods determine clinical analytical characteristics diagnosis approach treatment options patients cholangiocarcinoma according location retrospective analysis patients diagnosis cholangiocarcinoma last 5 years tertiary referral center results 89 patients 55 male followed median 23 weeks p25 75 8 80 progressive increase number cholangiocarcinoma diagnosis since beginning cohort 14 new diagnoses 2008 2009 31 2010 2011 44 2012 2013 mortality rate 6 months 40 5 median survival 164 days p25 75 61 566 patients 53 presented perihilar 24 extrahepatic 24 intrahepatic cholangiocarcinoma icc median age diagnosis 71 years lower icc 68 vs 74 p 0 014 diagnosis obtained using imaging methods 73 cases abdominal computed tomography common method 45 statistically significant correlation diagnosis icc need histological methods make diagnose p 0 001 serum levels g gt alkaline phophatase total bilirrubin diagnosis lower icc p 0 001 36 cases metastatic disease diagnosis hepatic metastization common disease 12 56 cases palliative treatment decided diagnosis 54 patients underwent surgery hepatectomy common intervention performed 20 cases conclusion icc presents less cholestasis diagnosis frequent need histological diagnosis type cholangiocarcinoma increase incidence cholangiocarcinoma verified cohort google scholar","probabilities":0.9799733,"Title":"Characterization Of Cholangiocarcinomas: Clinical And Topographic Features Of A Growing Oncological Reality","Abstract":"INTRODUCTION: Cholangiocarcinomas account for 3% of the malignant gastrointestinal neoplasms. The incidence of intra-hepatic cholangiocarcinomas has increased for unknown reasons [1.2].\nAIMS & METHODS: To determine the clinical and analytical characteristics, the diagnosis approach and the treatment options for patients with cholangiocarcinoma according to its location. Retrospective analysis of patients with diagnosis of cholangiocarcinoma in the last 5 years in a tertiary referral center.\nRESULTS: 89 patients (55% male) were followed for a median of 23 weeks (P25-75: 8-80). There was a progressive increase in the number of cholangiocarcinoma diagnosis since the beginning of the cohort (14 new diagnoses in 2008-2009, 31 in 2010-2011 and 44 in 2012-2013). The mortality rate at 6 months was 40.5% and the median survival was 164 days (P25-75: 61-566). Most patients (53%) presented perihilar, 24% extrahepatic and 24% intrahepatic cholangiocarcinoma (ICC). The median age at diagnosis was 71 years, being lower in the ICC (68 vs 74, p = 0.014). The diagnosis was obtained using imaging methods in 73% of cases, the abdominal computed tomography was the most common method (45%). There was a statistically significant correlation between the diagnosis of ICC and the need of histological methods to make a diagnose (p<0.001). Serum levels of G-GT, alkaline phophatase and total bilirrubin at diagnosis were lower in ICC (p<0.001). In 36% of cases there was metastatic disease at diagnosis, being hepatic metastization the most common disease (12%). In 56% of cases palliative treatment was decided at diagnosis and in 54% of the patients underwent surgery. Hepatectomy was the most common intervention and was performed in 20% of the cases.\nCONCLUSION: ICC presents with less cholestasis at diagnosis. It is more frequent the need for a histological diagnosis in this type of cholangiocarcinoma. An increase of the incidence of cholangiocarcinoma was verified in this cohort.","Source":"Google Scholar","category":"HUMAN","training_data":"Characterization Of Cholangiocarcinomas: Clinical And Topographic Features Of A Growing Oncological Reality INTRODUCTION: Cholangiocarcinomas account for 3% of the malignant gastrointestinal neoplasms. The incidence of intra-hepatic cholangiocarcinomas has increased for unknown reasons [1.2].\nAIMS & METHODS: To determine the clinical and analytical characteristics, the diagnosis approach and the treatment options for patients with cholangiocarcinoma according to its location. Retrospective analysis of patients with diagnosis of cholangiocarcinoma in the last 5 years in a tertiary referral center.\nRESULTS: 89 patients (55% male) were followed for a median of 23 weeks (P25-75: 8-80). There was a progressive increase in the number of cholangiocarcinoma diagnosis since the beginning of the cohort (14 new diagnoses in 2008-2009, 31 in 2010-2011 and 44 in 2012-2013). The mortality rate at 6 months was 40.5% and the median survival was 164 days (P25-75: 61-566). Most patients (53%) presented perihilar, 24% extrahepatic and 24% intrahepatic cholangiocarcinoma (ICC). The median age at diagnosis was 71 years, being lower in the ICC (68 vs 74, p = 0.014). The diagnosis was obtained using imaging methods in 73% of cases, the abdominal computed tomography was the most common method (45%). There was a statistically significant correlation between the diagnosis of ICC and the need of histological methods to make a diagnose (p<0.001). Serum levels of G-GT, alkaline phophatase and total bilirrubin at diagnosis were lower in ICC (p<0.001). In 36% of cases there was metastatic disease at diagnosis, being hepatic metastization the most common disease (12%). In 56% of cases palliative treatment was decided at diagnosis and in 54% of the patients underwent surgery. Hepatectomy was the most common intervention and was performed in 20% of the cases.\nCONCLUSION: ICC presents with less cholestasis at diagnosis. It is more frequent the need for a histological diagnosis in this type of cholangiocarcinoma. An increase of the incidence of cholangiocarcinoma was verified in this cohort. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"surgical treatment unsuspected gallbladder carcinoma detected cholecystectomy aims carcinoma detected histological examination gallbladder cholecystectomy gallstone disease acute cholecystitis defined incidental fairly rare event increase number cholecystectomies performed result success laparoscopic technique led rise number incidental carcinomas detected histologically cases pt1a pt1b pt2 carcinomas e tumours penetrate beyond muscular wall gallbladder nineties believed carcinomas adequately treated simple cholecystectomy whereas today treatment choice entails radical second operation methods study conducted single institute constitutes review 30 years experience data base consists 3530 cholecystectomies 0 878 incidence incidental gallbladder carcinoma 32 patients unsuspected carcinoma 3 pt1a 6 pt1b 23 pt2 results survival data carefully calculated relation evolution surgical treatment years thus making possible correlate tumour staging patient survival surgical therapy conclusions contributions made literature reports since nineties prompted hepatobiliary surgeons modify attitudes towards incidental gallbladder carcinoma detection previously unrecognised microinfiltrations serosa neoplastic involvement distant lymph node stations led introduction concepts radical extended cholecystectomy pt1b pt2 patients comparison historical survival curves patients treated simple cholecystectomy distinctly better curves treated radical second operation accounts evolution surgical treatment past two decades google scholar","probabilities":0.9799733,"Title":"The Surgical Treatment Of Unsuspected Gallbladder Carcinoma Detected After Cholecystectomy","Abstract":"Aims: Carcinoma detected at histological examination of the gallbladder after cholecystectomy for gallstone disease or acute cholecystitis is defined as incidental. It is a fairly rare event, but the increase in the number of cholecystectomies performed as a result of the success of the laparoscopic technique has led to a rise in the number of incidental carcinomas detected. Histologically, in most cases, these are pT1A, pT1B and pT2 carcinomas, i.e., tumours that do not penetrate beyond the muscular wall of the gallbladder. Up until the ‘nineties it was believed that these carcinomas could be adequately treated by simple cholecystectomy, whereas today the treatment of choice entails a radical second operation.\nMethods: This study, conducted at a single institute, constitutes a review of 30 years’ experience: the data base consists of 3530 cholecystectomies with a 0.878% incidence of incidental gallbladder carcinoma (32 patients with unsuspected carcinoma: 3 pT1a, 6 pT1b, 23 pT2).\nResults: Survival data are carefully calculated in relation to the evolution of surgical treatment over the years, thus making it possible to correlate tumour staging, patient survival and surgical therapy\nConclusions: The contributions made by literature reports since the ‘nineties have prompted hepatobiliary surgeons to modify their attitudes towards incidental gallbladder carcinoma. Detection of previously unrecognised microinfiltrations of the serosa and of neoplastic involvement of distant lymph-node stations has led to the introduction of the concepts of radical and extended cholecystectomy for pT1b and pT2 patients. Comparison between the historical survival curves of patients treated with simple cholecystectomy and the distinctly better curves of those treated with a radical second operation accounts for the evolution of surgical treatment over the past two decades","Source":"Google Scholar","category":"HUMAN","training_data":"The Surgical Treatment Of Unsuspected Gallbladder Carcinoma Detected After Cholecystectomy Aims: Carcinoma detected at histological examination of the gallbladder after cholecystectomy for gallstone disease or acute cholecystitis is defined as incidental. It is a fairly rare event, but the increase in the number of cholecystectomies performed as a result of the success of the laparoscopic technique has led to a rise in the number of incidental carcinomas detected. Histologically, in most cases, these are pT1A, pT1B and pT2 carcinomas, i.e., tumours that do not penetrate beyond the muscular wall of the gallbladder. Up until the ‘nineties it was believed that these carcinomas could be adequately treated by simple cholecystectomy, whereas today the treatment of choice entails a radical second operation.\nMethods: This study, conducted at a single institute, constitutes a review of 30 years’ experience: the data base consists of 3530 cholecystectomies with a 0.878% incidence of incidental gallbladder carcinoma (32 patients with unsuspected carcinoma: 3 pT1a, 6 pT1b, 23 pT2).\nResults: Survival data are carefully calculated in relation to the evolution of surgical treatment over the years, thus making it possible to correlate tumour staging, patient survival and surgical therapy\nConclusions: The contributions made by literature reports since the ‘nineties have prompted hepatobiliary surgeons to modify their attitudes towards incidental gallbladder carcinoma. Detection of previously unrecognised microinfiltrations of the serosa and of neoplastic involvement of distant lymph-node stations has led to the introduction of the concepts of radical and extended cholecystectomy for pT1b and pT2 patients. Comparison between the historical survival curves of patients treated with simple cholecystectomy and the distinctly better curves of those treated with a radical second operation accounts for the evolution of surgical treatment over the past two decades Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"eus guided gallbladder drainage rescue treatment malignant distal biliary obstruction unsuccessful ercp background aims eus guided bile duct drainage eus bd well recognized rescue biliary drainage method unsuccessful ercp eus guided gallbladder drainage eus gbd recently used treat acute cholecystitis aim study assess efficacy safety eus gbd malignant biliary stricture induced obstructive jaundice unsuccessful ercp well unsuccessful impractical eus bd methods january 2006 october 2014 12 patients obstructive jaundice due unresectable malignant distal biliary stricture underwent eus gbd ercp failed eus gbd performed guidance eus fluoroscopy puncturing gallbladder needle inserting guidewire dilating puncture hole placing stent technical functional success rates adverse events rate overall patient survival time stent dysfunction rate patient survival measured results rates technical success functional success adverse events stent dysfunction 100 91 7 16 7 8 3 respectively median survival time eus gbd 105 days range 15 236 days conclusions eus gbd possible alternative route decompression biliary system ercp unsuccessful pubmed","probabilities":0.9799733,"Title":"EUS-guided gallbladder drainage for rescue treatment of malignant distal biliary obstruction after unsuccessful ERCP","Abstract":"BACKGROUND AND AIMS: EUS-guided bile duct drainage (EUS-BD) is a well-recognized rescue biliary drainage method after unsuccessful ERCP. EUS-guided gallbladder drainage (EUS-GBD) was recently used to treat acute cholecystitis. The aim of this study was to assess the efficacy and safety of EUS-GBD for malignant biliary stricture-induced obstructive jaundice after unsuccessful ERCP as well as unsuccessful or impractical EUS-BD. METHODS: Between January 2006 and October 2014, 12 patients with obstructive jaundice due to unresectable malignant distal biliary stricture underwent EUS-GBD after ERCP failed. EUS-GBD was performed under the guidance of EUS and fluoroscopy by puncturing the gallbladder with a needle, inserting a guidewire, dilating the puncture hole, and placing a stent. The technical and functional success rates, adverse events rate, overall patient survival time, and stent dysfunction rate during patient survival were measured. RESULTS: The rates of technical success, functional success, adverse events, and stent dysfunction were 100%, 91.7%, 16.7%, and 8.3%, respectively. The median survival time after EUS-GBD was 105 days (range 15 - 236 days). CONCLUSIONS: EUS-GBD is a possible alternative route for decompression of the biliary system when ERCP is unsuccessful.","Source":"PubMed","category":"HUMAN","training_data":"EUS-guided gallbladder drainage for rescue treatment of malignant distal biliary obstruction after unsuccessful ERCP BACKGROUND AND AIMS: EUS-guided bile duct drainage (EUS-BD) is a well-recognized rescue biliary drainage method after unsuccessful ERCP. EUS-guided gallbladder drainage (EUS-GBD) was recently used to treat acute cholecystitis. The aim of this study was to assess the efficacy and safety of EUS-GBD for malignant biliary stricture-induced obstructive jaundice after unsuccessful ERCP as well as unsuccessful or impractical EUS-BD. METHODS: Between January 2006 and October 2014, 12 patients with obstructive jaundice due to unresectable malignant distal biliary stricture underwent EUS-GBD after ERCP failed. EUS-GBD was performed under the guidance of EUS and fluoroscopy by puncturing the gallbladder with a needle, inserting a guidewire, dilating the puncture hole, and placing a stent. The technical and functional success rates, adverse events rate, overall patient survival time, and stent dysfunction rate during patient survival were measured. RESULTS: The rates of technical success, functional success, adverse events, and stent dysfunction were 100%, 91.7%, 16.7%, and 8.3%, respectively. The median survival time after EUS-GBD was 105 days (range 15 - 236 days). CONCLUSIONS: EUS-GBD is a possible alternative route for decompression of the biliary system when ERCP is unsuccessful. PubMed","prediction_labels":"HUMAN"},{"cleaned":"liver transplantation cholangiocarcinoma current best practice purpose review cholangiocarcinoma rare tumour dismal prognosis radical resection offers chance cure reported survivals ranging 25 45 5 years considering low rate resectability lack efficacy treatments liver transplantation emerged reasonable approach cure selective patients unresectable diseases use liver transplantation however associated inherent risk early tumour recurrence due need immunosuppression poor survival rate review focus role liver transplantation treating patients cholangiocellular cancer recent findings indication liver transplantation cholangiocarcinoma evolved time moving absolute relative contraindication eventually becoming best indication small group patients presenting unresectable perihilar cholangiocarcinoma associated neoadjuvant chemoradiotherapy contrast indication liver transplantation intrahepatic cholangiocarcinoma far established offered protocol mainly small tumours setting cirrhosis summary poor outcome cholangiocarcinoma irrespective therapy justifies search novel approaches selective patients perihilar cholangiocarcinoma subjected neoadjuvant protocol may qualify liver transplantation pubmed","probabilities":0.9799733,"Title":"Liver transplantation for cholangiocarcinoma: current best practice","Abstract":"PURPOSE OF REVIEW: Cholangiocarcinoma is a rare tumour with dismal prognosis. Only radical resection offers a chance for cure with reported survivals ranging from 25 to 45% at 5 years. Considering the low rate of resectability and lack of efficacy of other treatments, liver transplantation has emerged as a reasonable approach to cure selective patients with unresectable diseases. The use of liver transplantation, however, is associated with the inherent risk of early tumour recurrence due to the need for immunosuppression and the poor survival rate. This review will focus on the role of liver transplantation in treating patients with cholangiocellular cancer. RECENT FINDINGS: The indication of liver transplantation for cholangiocarcinoma has evolved over time moving from an absolute to a relative contraindication until eventually becoming the best indication for a small group of patients presenting with unresectable perihilar cholangiocarcinoma, when associated with a neoadjuvant chemoradiotherapy. In contrast, the indication of liver transplantation for intrahepatic cholangiocarcinoma is far from being established and should be offered only under protocol, mainly for small tumours in the setting of cirrhosis. SUMMARY: The poor outcome of cholangiocarcinoma, irrespective of the therapy, justifies the search for novel approaches. Only selective patients with perihilar cholangiocarcinoma subjected to a neoadjuvant protocol may qualify for liver transplantation.","Source":"PubMed","category":"HUMAN","training_data":"Liver transplantation for cholangiocarcinoma: current best practice PURPOSE OF REVIEW: Cholangiocarcinoma is a rare tumour with dismal prognosis. Only radical resection offers a chance for cure with reported survivals ranging from 25 to 45% at 5 years. Considering the low rate of resectability and lack of efficacy of other treatments, liver transplantation has emerged as a reasonable approach to cure selective patients with unresectable diseases. The use of liver transplantation, however, is associated with the inherent risk of early tumour recurrence due to the need for immunosuppression and the poor survival rate. This review will focus on the role of liver transplantation in treating patients with cholangiocellular cancer. RECENT FINDINGS: The indication of liver transplantation for cholangiocarcinoma has evolved over time moving from an absolute to a relative contraindication until eventually becoming the best indication for a small group of patients presenting with unresectable perihilar cholangiocarcinoma, when associated with a neoadjuvant chemoradiotherapy. In contrast, the indication of liver transplantation for intrahepatic cholangiocarcinoma is far from being established and should be offered only under protocol, mainly for small tumours in the setting of cirrhosis. SUMMARY: The poor outcome of cholangiocarcinoma, irrespective of the therapy, justifies the search for novel approaches. Only selective patients with perihilar cholangiocarcinoma subjected to a neoadjuvant protocol may qualify for liver transplantation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"single center analysis survival benefits adjuvant gemcitabine chemotherapy biliary tract cancer background surgical resection curative treatment biliary tract cancer btc however prognosis btc remains unsatisfactory aim study evaluate benefits adjuvant gemcitabine chemotherapy btc methods performed historical cohort study involved 198 patients underwent r0 surgical resection patients underwent major hepatectomy administered biweekly intravenous gemcitabine dose 800 mg m 2 otherwise patients administered intravenous gemcitabine dose 1 000 mg m 2 3 weekly infusions followed 1 week pause primary outcome overall survival hazard ratio hr adjuvant chemotherapy estimated propensity score stratified cox regression adjusted confounders results forty patients received adjuvant chemotherapy hr adjuvant chemotherapy 0 47 95 confidence interval ci 0 28 0 95 p 0 03 subgroup analysis showed survival benefits possibly modified lymph node positivity hr 0 19 95 ci 0 07 0 58 interaction p 0 22 stage iii hr 0 11 95 ci 0 02 0 50 interaction p 0 01 intrahepatic cholangiocarcinoma icc hr 0 09 95 ci 0 01 0 67 interaction p 0 05 poorly differentiated tumor hr 0 16 95 ci 0 03 0 85 interaction p 0 13 conclusions adjuvant gemcitabine chemotherapy btc may effective particularly patients stage iii icc stn","probabilities":0.9799733,"Title":"A Single-Center Analysis Of The Survival Benefits Of Adjuvant Gemcitabine Chemotherapy For Biliary Tract Cancer","Abstract":"Background: Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC. \r\n\r\n Methods: We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m(2). Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m(2) in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders. \r\n\r\n Results: Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28-0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07-0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02-0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01-0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03-0.85; interaction, P = 0.13). \r\n\r\n Conclusions: Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC.","Source":"STN","category":"HUMAN","training_data":"A Single-Center Analysis Of The Survival Benefits Of Adjuvant Gemcitabine Chemotherapy For Biliary Tract Cancer Background: Surgical resection is the only curative treatment of biliary tract cancer (BTC). However, the prognosis of BTC remains unsatisfactory. The aim of this study is to evaluate the benefits of adjuvant gemcitabine chemotherapy for BTC. \r\n\r\n Methods: We performed a historical cohort study that involved 198 patients who underwent R0 surgical resection. Patients who underwent major hepatectomy were administered biweekly intravenous gemcitabine at a dose of 800 mg/m(2). Otherwise, patients were administered intravenous gemcitabine at a dose of 1,000 mg/m(2) in 3 weekly infusions, which were followed by a 1-week pause. The primary outcome was overall survival. The hazard ratio (HR) of adjuvant chemotherapy was estimated by propensity score-stratified Cox regression that was adjusted for confounders. \r\n\r\n Results: Forty patients received adjuvant chemotherapy. The HR of adjuvant chemotherapy was 0.47 [95 % confidence interval (CI) 0.28-0.95; P = 0.03]. Subgroup analysis showed that the survival benefits were possibly modified by lymph node positivity (HR 0.19; 95 % CI 0.07-0.58; interaction, P = 0.22), stage III (HR 0.11; 95 % CI 0.02-0.50; interaction, P < 0.01), intrahepatic cholangiocarcinoma (ICC) (HR 0.09; 95 % CI 0.01-0.67; interaction, P = 0.05), and poorly differentiated tumor (HR 0.16; 95 % CI 0.03-0.85; interaction, P = 0.13). \r\n\r\n Conclusions: Adjuvant gemcitabine chemotherapy for BTC may be effective, particularly for patients with stage III and ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"digitalis use risk gastrointestinal cancers nationwide population based cohort study background gastrointestinal cancers characterized male predominance suggesting role sex hormones hypothesized digitalis medication due estrogenic properties decreases risk male predominated gastrointestinal cancers results long term digitalis use 2 years followed decreased risk several gastrointestinal cancers associations statistically significant liver cancer hazard ratio hr 0 40 95 confidence interval ci 0 16 0 98 short term 1 year use associated increased risk esophageal squamous cell carcinoma hr 1 79 95 ci 1 01 3 17 colorectal cancer hr 1 72 95 ci 1 57 1 89 gallbladder cancer hr 1 93 95 ci 1 04 3 59 pancreatic cancer hr 1 33 95 ci 1 00 1 76 increase found among long term users methods performed nationwide population based cohort study sweden participants included 156 385 individuals using digitalis reference group 551 933 users organic nitrates 2005 2013 identified swedish prescribed drug register new diagnoses gastrointestinal cancers identified swedish cancer register hazard ratios gastrointestinal cancers digitalis users compared users organic nitrates calculated cox proportional hazards regression adjustment sex age municipality residence comorbidity conclusions study suggests decreased risk male predominated gastrointestinal cancers particularly liver cancer long term users digitalis short term use may associated increased risk esophageal squamous cell carcinoma colorectal cancer gallbladder cancer pancreatic cancer use digitalis preventive therapeutic agents remains fully evaluated pubmed","probabilities":0.962963,"Title":"Digitalis use and risk of gastrointestinal cancers: A nationwide population-based cohort study","Abstract":"BACKGROUND: Gastrointestinal cancers are characterized by a male predominance, suggesting a role of sex hormones. We hypothesized that digitalis medication, due to its estrogenic properties, decreases the risk of male-predominated gastrointestinal cancers. RESULTS: Long -term digitalis use (≥2 years) was followed by decreased risk for several gastrointestinal cancers, but associations were statistically significant only for liver cancer (hazard ratio [HR]=0.40, 95% confidence interval (CI) 0.16-0.98). Short-term (<1 year) use was associated with an increased risk of esophageal squamous cell carcinoma (HR=1.79, 95% CI 1.01-3.17), colorectal cancer (HR=1.72, 95% CI 1.57-1.89), gallbladder cancer (HR=1.93, 95% CI 1.04-3.59), and pancreatic cancer (HR=1.33, 95% CI 1.00-1.76), but no such increase was found among long-term users. METHODS: We performed a nationwide population-based cohort study in Sweden. Participants included 156,385 individuals using digitalis and a reference group of 551,933 users of organic nitrates between 2005 and 2013, who were identified in the Swedish Prescribed Drug Register. New diagnoses of gastrointestinal cancers were identified from the Swedish Cancer Register. Hazard ratios of gastrointestinal cancers in digitalis users compared to users of organic nitrates were calculated from Cox proportional hazards regression with adjustment for sex, age, municipality of residence and comorbidity. CONCLUSIONS: This study suggests a decreased risk of male-predominated gastrointestinal cancers, particularly of liver cancer, in long-term users of digitalis. Short-term use may be associated with an increased risk of esophageal squamous cell carcinoma, colorectal cancer, gallbladder cancer, and pancreatic cancer.The use of digitalis as preventive or therapeutic agents remains to be fully evaluated.","Source":"PubMed","category":"HUMAN","training_data":"Digitalis use and risk of gastrointestinal cancers: A nationwide population-based cohort study BACKGROUND: Gastrointestinal cancers are characterized by a male predominance, suggesting a role of sex hormones. We hypothesized that digitalis medication, due to its estrogenic properties, decreases the risk of male-predominated gastrointestinal cancers. RESULTS: Long -term digitalis use (≥2 years) was followed by decreased risk for several gastrointestinal cancers, but associations were statistically significant only for liver cancer (hazard ratio [HR]=0.40, 95% confidence interval (CI) 0.16-0.98). Short-term (<1 year) use was associated with an increased risk of esophageal squamous cell carcinoma (HR=1.79, 95% CI 1.01-3.17), colorectal cancer (HR=1.72, 95% CI 1.57-1.89), gallbladder cancer (HR=1.93, 95% CI 1.04-3.59), and pancreatic cancer (HR=1.33, 95% CI 1.00-1.76), but no such increase was found among long-term users. METHODS: We performed a nationwide population-based cohort study in Sweden. Participants included 156,385 individuals using digitalis and a reference group of 551,933 users of organic nitrates between 2005 and 2013, who were identified in the Swedish Prescribed Drug Register. New diagnoses of gastrointestinal cancers were identified from the Swedish Cancer Register. Hazard ratios of gastrointestinal cancers in digitalis users compared to users of organic nitrates were calculated from Cox proportional hazards regression with adjustment for sex, age, municipality of residence and comorbidity. CONCLUSIONS: This study suggests a decreased risk of male-predominated gastrointestinal cancers, particularly of liver cancer, in long-term users of digitalis. Short-term use may be associated with an increased risk of esophageal squamous cell carcinoma, colorectal cancer, gallbladder cancer, and pancreatic cancer.The use of digitalis as preventive or therapeutic agents remains to be fully evaluated. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role ytrrium 90 treatment unresectable metastatic intrahepatic cholangiocarcinoma background selective internal radiation therapy sirt ytrrium 90 y 90 used treat hepatic malignancies success study focuses efficacy safety y 90 treatment unresectable metastatic intrahepatic cholangiocarcinoma icc methods single institution retrospective case review performed patients unresectable metastatic icc treated y 90 2006 2016 results seventeen patients icc underwent 21 y 90 treatments four patients undergone prior liver resection six patients extrahepatic disease time treatment five year overall survival 26 8 median survival 33 6 months one patient underwent margin negative liver resection single treatment complications appreciated two cases ninety day mortality 0 conclusion treatment icc using y 90 safe promising procedure research needed clarify role treatment unresectable metastatic icc pubmed","probabilities":0.9799733,"Title":"Is there a role for Ytrrium-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma?","Abstract":"BACKGROUND: Selective internal radiation therapy (SIRT) with Ytrrium-90 (Y-90) has been used to treat hepatic malignancies with success. This study focuses on the efficacy and safety of Y-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma (ICC). METHODS: A single-institution retrospective case review was performed for patients with unresectable and metastatic ICC treated with Y-90 between 2006 and 2016. RESULTS: Seventeen patients with ICC underwent 21 Y-90 treatments. Four patients had undergone prior liver resection, and six patients had extrahepatic disease at the time of treatment. Five year overall survival was 26.8%, with a median survival of 33.6 months. One patient underwent margin negative liver resection after a single treatment. Complications were appreciated in two cases. Ninety-day mortality was 0%. CONCLUSION: Treatment of ICC using Y-90 is a safe and promising procedure. Further research is needed to clarify its role in the treatment of unresectable and metastatic ICC.","Source":"PubMed","category":"HUMAN","training_data":"Is there a role for Ytrrium-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma? BACKGROUND: Selective internal radiation therapy (SIRT) with Ytrrium-90 (Y-90) has been used to treat hepatic malignancies with success. This study focuses on the efficacy and safety of Y-90 in the treatment of unresectable and metastatic intrahepatic cholangiocarcinoma (ICC). METHODS: A single-institution retrospective case review was performed for patients with unresectable and metastatic ICC treated with Y-90 between 2006 and 2016. RESULTS: Seventeen patients with ICC underwent 21 Y-90 treatments. Four patients had undergone prior liver resection, and six patients had extrahepatic disease at the time of treatment. Five year overall survival was 26.8%, with a median survival of 33.6 months. One patient underwent margin negative liver resection after a single treatment. Complications were appreciated in two cases. Ninety-day mortality was 0%. CONCLUSION: Treatment of ICC using Y-90 is a safe and promising procedure. Further research is needed to clarify its role in the treatment of unresectable and metastatic ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"early gallbladder carcinoma favorable outcome rokitansky aschoff sinus involvement adverse prognostic factor general impression gallbladder carcinomas uniformly fatal however early forms entirely different picture indicating good prognosis evolving high incidence regions subjected 190 early gallbladder carcinomas egbc defined carcinomas confined tunica muscularis ajcc tis t1a t1b identified cholecystectomy specimens sampled entirely according established protocol detailed analysis average patient age 57 9 years 29 95 half cases 114 190 60 tumor inapparent gross examination 81 cases 42 6 carcinomatous epithelium abutted muscularis whereas 57 4 n 109 qualified intramucosal overt contiguity muscularis intraepithelial extension rokitansky aschoff sinuses ras found 34 cases 17 8 time data analysis 171 patients 90 corrected alive overall actuarial survival 92 3 5 years 90 4 10 years 5 10 year actuarial survival rates intramucosal group 93 2 92 1 respectively statistically different muscle abutting group 89 7 88 2 p 0 334 patients ras involvement significantly shorter survival without p 0 001 33 patients ras involvement 13 39 died disease whereas 6 154 patients 4 without ras involvement died disease disease related mortality cases occurred relatively late median 48 months egbc good prognosis 90 10 year survival rate seen average patients almost decade younger advanced cancers ras involvement independent prognostic factor additional surgery may considered cases occasional recurrences encountered several years later suggests field effect phenomenon warrants long term follow stn","probabilities":0.9799733,"Title":"Early Gallbladder Carcinoma Has A Favorable Outcome But Rokitansky-Aschoff Sinus Involvement Is An Adverse Prognostic Factor","Abstract":"The general impression about gallbladder carcinomas is that they are uniformly fatal; however, for the early forms, an entirely different picture indicating a very good prognosis is evolving from the high-incidence regions. We subjected 190 early gallbladder carcinomas (EGBC), defined as carcinomas confined to and above the tunica muscularis (AJCC's Tis, T1a, and T1b), and identified in cholecystectomy specimens sampled entirely according to an established protocol, to detailed analysis. Average patient age was 57.9 years (29-95). In more than half of the cases (114/190; 60%), the tumor was inapparent by gross examination. In 81 cases (42.6%), carcinomatous epithelium abutted the muscularis, whereas 57.4 % (n = 109) were qualified as intramucosal with no overt contiguity with muscularis.Intraepithelial extension into Rokitansky–Aschoff sinuses (RAS) was found in 34 cases (17.8 %). At the time of data analysis, 171 patients (90 %) [corrected] were alive. Overall actuarial survival was 92.3 % at 5 years and 90.4 % at 10 years. The 5- and 10-year actuarial survival rates of the intramucosal group (93.2 and 92.1%, respectively) were not statistically different from that of the muscle-abutting group (89.7% and 88.2% ; p = 0.334). Patients with RAS involvement had a significantly shorter survival than those without (p < 0.001). Of the 33 patients with RAS involvement, 13 (39%) died of disease, whereas only 6 of the 154 patients (4%) without RAS involvement died of disease. Disease-related mortality in these cases occurred relatively late (median 48 months). EGBC has a very good prognosis with a 90% 10-year survival rate. It is seen on average in patients almost a decade younger than those with advanced cancers. RAS involvement is an independent prognostic factor, and additional surgery may have to be considered for such cases. Occasional recurrences are encountered several years later, which suggests a field-effect phenomenon and warrants long-term follow-up.","Source":"STN","category":"HUMAN","training_data":"Early Gallbladder Carcinoma Has A Favorable Outcome But Rokitansky-Aschoff Sinus Involvement Is An Adverse Prognostic Factor The general impression about gallbladder carcinomas is that they are uniformly fatal; however, for the early forms, an entirely different picture indicating a very good prognosis is evolving from the high-incidence regions. We subjected 190 early gallbladder carcinomas (EGBC), defined as carcinomas confined to and above the tunica muscularis (AJCC's Tis, T1a, and T1b), and identified in cholecystectomy specimens sampled entirely according to an established protocol, to detailed analysis. Average patient age was 57.9 years (29-95). In more than half of the cases (114/190; 60%), the tumor was inapparent by gross examination. In 81 cases (42.6%), carcinomatous epithelium abutted the muscularis, whereas 57.4 % (n = 109) were qualified as intramucosal with no overt contiguity with muscularis.Intraepithelial extension into Rokitansky–Aschoff sinuses (RAS) was found in 34 cases (17.8 %). At the time of data analysis, 171 patients (90 %) [corrected] were alive. Overall actuarial survival was 92.3 % at 5 years and 90.4 % at 10 years. The 5- and 10-year actuarial survival rates of the intramucosal group (93.2 and 92.1%, respectively) were not statistically different from that of the muscle-abutting group (89.7% and 88.2% ; p = 0.334). Patients with RAS involvement had a significantly shorter survival than those without (p < 0.001). Of the 33 patients with RAS involvement, 13 (39%) died of disease, whereas only 6 of the 154 patients (4%) without RAS involvement died of disease. Disease-related mortality in these cases occurred relatively late (median 48 months). EGBC has a very good prognosis with a 90% 10-year survival rate. It is seen on average in patients almost a decade younger than those with advanced cancers. RAS involvement is an independent prognostic factor, and additional surgery may have to be considered for such cases. Occasional recurrences are encountered several years later, which suggests a field-effect phenomenon and warrants long-term follow-up. STN","prediction_labels":"HUMAN"},{"cleaned":"nomogram predict lymph node metastasis resection intrahepatic cholangiocarcinoma background study developed validated nomogram predict lymph node metastasis surgery patients intrahepatic cholangiocarcinoma icc methods using data january 2006 january 2015 enrolled total 218 eligible patients clinicopathologically confirmed icc primary cohort develop nomogram various variables surgery analyzed multivariable logistic regression combined preoperative carbohydrate antigen 19 9 primary site tumor lymphonodus size computed tomography imaging tumor growth pattern applicable histologic grade make two different predictive nomograms results validated 62 consecutive icc patients february 2015 december 2016 also compared performance different nomograms via calibration discrimination clinical use results nomogram displayed fine discrimination concordance index 0 761 fine calibration primary cohort applied validation cohort nomogram also showed fine discrimination concordance index 0 794 fine calibration adding histologic grade nomogram integrated discrimination predictive performance improved significantly finally clinical usefulness predictive nomogram proven via decision curve analysis conclusions proposed nomograms selectively used achieve accurate lymph node metastasis predictions surgery patients icc information help clinical management google scholar","probabilities":0.9799733,"Title":"A Nomogram To Predict Lymph Node Metastasis Before Resection In Intrahepatic Cholangiocarcinoma","Abstract":"Background\nIn this study, we developed and validated a nomogram to predict lymph node metastasis before surgery in patients with intrahepatic cholangiocarcinoma (ICC).\nMethods\nUsing the data from January 2006 to January 2015, we enrolled a total of 218 eligible patients with clinicopathologically confirmed ICC as a primary cohort to develop the nomogram. After various variables before surgery were analyzed by multivariable logistic regression, we combined the preoperative carbohydrate antigen 19-9, primary site of tumor, lymphonodus size on computed tomography imaging, tumor growth pattern, and (if applicable) histologic grade to make two different predictive nomograms. Then, the results were validated in 62 consecutive ICC patients from February 2015 to December 2016. We also compared the performance of the different nomograms via calibration, discrimination, and clinical use.\nResults\nThe nomogram displayed fine discrimination (the concordance index, 0.761) and fine calibration in the primary cohort. When applied to the validation cohort, the nomogram also showed fine discrimination (concordance index, 0.794) and fine calibration. After adding the histologic grade to the nomogram, the integrated discrimination for predictive performance improved significantly. Finally, the clinical usefulness of predictive nomogram was proven via the decision curve analysis.\nConclusions\nThe proposed nomograms can be selectively used to achieve more accurate lymph node metastasis predictions before surgery in patients with ICC, and this information can help with clinical management.","Source":"Google Scholar","category":"HUMAN","training_data":"A Nomogram To Predict Lymph Node Metastasis Before Resection In Intrahepatic Cholangiocarcinoma Background\nIn this study, we developed and validated a nomogram to predict lymph node metastasis before surgery in patients with intrahepatic cholangiocarcinoma (ICC).\nMethods\nUsing the data from January 2006 to January 2015, we enrolled a total of 218 eligible patients with clinicopathologically confirmed ICC as a primary cohort to develop the nomogram. After various variables before surgery were analyzed by multivariable logistic regression, we combined the preoperative carbohydrate antigen 19-9, primary site of tumor, lymphonodus size on computed tomography imaging, tumor growth pattern, and (if applicable) histologic grade to make two different predictive nomograms. Then, the results were validated in 62 consecutive ICC patients from February 2015 to December 2016. We also compared the performance of the different nomograms via calibration, discrimination, and clinical use.\nResults\nThe nomogram displayed fine discrimination (the concordance index, 0.761) and fine calibration in the primary cohort. When applied to the validation cohort, the nomogram also showed fine discrimination (concordance index, 0.794) and fine calibration. After adding the histologic grade to the nomogram, the integrated discrimination for predictive performance improved significantly. Finally, the clinical usefulness of predictive nomogram was proven via the decision curve analysis.\nConclusions\nThe proposed nomograms can be selectively used to achieve more accurate lymph node metastasis predictions before surgery in patients with ICC, and this information can help with clinical management. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"postoperative morbidity results decreased survival resection hilar cholangiocarcinoma background purpose present study demonstrate post operative morbidity pm associated resections hilar cholangiocarcinoma hcca associated short long term patient survival methods 1998 2008 51 patients median age 64 years underwent resection hcca single institution associations survival clinicopathologic factors including peri post operative variables studied using univariate multivariate models results seventy six per cent patients underwent major hepatectomy resection extrahepatic bile ducts 30 90 day operative mortality 10 12 overall incidence pm 69 68 pm major clavien grades iii v difference operative blood loss peri operative transfusion rates observed patients major vs minor pm patients major pm received adjuvant chemotherapy less frequently patients minor complications 29 vs 52 p 0 15 1 3 5 year overall os disease specific survival dss rates patients 65 36 29 77 46 35 respectively using univariate multivariate analysis margin status 27 r1 nodal metastasis 35 n1 major pm associated os dss p 0 01 major pm independent factor associated decreased os dss hazard ratio hr 3 6 2 8 respectively p 0 05 median dss patients major pm 14 months compared 40 months patients experienced minor pm p 0 01 conclusion extensive operations hcca produce substantial post operative morbidity addition causing early mortality major post operative complications associated decreased long term cancer specific survival resection hcca google scholar","probabilities":0.9799733,"Title":"Postoperative Morbidity Results In Decreased Survival After Resection For Hilar Cholangiocarcinoma","Abstract":"Background\nThe purpose of the present study was to demonstrate that post-operative morbidity (PM) associated with resections of hilar cholangiocarcinoma (HCCA) is associated with short- and long-term patient survival.\nMethods\nBetween 1998 and 2008, 51 patients with a median age of 64 years underwent resection for HCCA at a single institution. Associations between survival and clinicopathologic factors, including peri- and post-operative variables, were studied using univariate and multivariate models.\nResults\nSeventy-six per cent of patients underwent major hepatectomy with resection of the extrahepatic bile ducts. The 30- and 90-day operative mortality was 10% and 12%. The overall incidence of PM was 69%, with 68% of all PM as major (Clavien grades III–V). No difference in operative blood loss or peri-operative transfusion rates was observed for patients with major vs. minor or no PM. Patients with major PM received adjuvant chemotherapy less frequently than patients with minor or no complications 29% vs. 52%, P= 0.15. The 1-, 3- and 5-year overall (OS) and disease-specific survival (DSS) rates for all patients were 65%, 36%, 29% and 77%, 46%, 35%, respectively. Using univariate and multivariate analysis, margin status (27% R1), nodal metastasis (35% N1) and major PM were associated with OS and DSS, P < 0.01. Major PM was an independent factor associated with decreased OS and DSS [hazard ratio (HR) = 3.6 and 2.8, respectively, P < 0.05]. The median DSS for patients with major PM was 14 months compared with 40 months for patients who experienced minor or no PM, P < 0.01.\nConclusion\nExtensive operations for HCCA can produce substantial post-operative morbidity. In addition to causing early mortality, major post-operative complications are associated with decreased long-term cancer-specific survival after resection of HCCA.","Source":"Google Scholar","category":"HUMAN","training_data":"Postoperative Morbidity Results In Decreased Survival After Resection For Hilar Cholangiocarcinoma Background\nThe purpose of the present study was to demonstrate that post-operative morbidity (PM) associated with resections of hilar cholangiocarcinoma (HCCA) is associated with short- and long-term patient survival.\nMethods\nBetween 1998 and 2008, 51 patients with a median age of 64 years underwent resection for HCCA at a single institution. Associations between survival and clinicopathologic factors, including peri- and post-operative variables, were studied using univariate and multivariate models.\nResults\nSeventy-six per cent of patients underwent major hepatectomy with resection of the extrahepatic bile ducts. The 30- and 90-day operative mortality was 10% and 12%. The overall incidence of PM was 69%, with 68% of all PM as major (Clavien grades III–V). No difference in operative blood loss or peri-operative transfusion rates was observed for patients with major vs. minor or no PM. Patients with major PM received adjuvant chemotherapy less frequently than patients with minor or no complications 29% vs. 52%, P= 0.15. The 1-, 3- and 5-year overall (OS) and disease-specific survival (DSS) rates for all patients were 65%, 36%, 29% and 77%, 46%, 35%, respectively. Using univariate and multivariate analysis, margin status (27% R1), nodal metastasis (35% N1) and major PM were associated with OS and DSS, P < 0.01. Major PM was an independent factor associated with decreased OS and DSS [hazard ratio (HR) = 3.6 and 2.8, respectively, P < 0.05]. The median DSS for patients with major PM was 14 months compared with 40 months for patients who experienced minor or no PM, P < 0.01.\nConclusion\nExtensive operations for HCCA can produce substantial post-operative morbidity. In addition to causing early mortality, major post-operative complications are associated with decreased long-term cancer-specific survival after resection of HCCA. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"verification wfa sialylated muc1 sensitive biliary biomarker human biliary tract cancer background diagnostic accuracy biliary cytology limited novel sandwich enzyme linked immunosorbent assay combined wisteria floribunda agglutinin wfa anti sialylated mucin 1 muc1 monoclonal antibody target bile samples recently developed study designed verify diagnostic accuracy wfa sialylated muc1 sensitive biliary biomarker human biliary tract cancer methods bile samples 27 patients benign disease 174 patients biliary tract cancer analyzed receiver operated characteristic curve analysis biliary wfa sialylated muc1 serum ca19 9 levels performed determine cutoff value prediction presence biliary tract cancer results biliary wfa sialylated muc1 levels significantly higher biliary tract cancer group compared benign group p 0 001 cutoff value wfa sialylated muc1 discriminating biliary tract cancer 10 5 sensitivity wfa sialylated muc1 discriminating biliary tract cancer much higher 82 2 cytology 23 6 cutoff value used cutoff value serum ca19 9 discriminating biliary tract cancer 38 iu l cohort patients biliary wfa sialylated muc1 serum ca19 9 cutoff values biliary tract cancer patient benign disease categorized group conclusions biliary wfa sialylated muc1 useful biomarker differentiation biliary tract cancer sensitivity wfa sialylated muc1 clearly higher biliary cytology data collection necessary validate clinical usefulness biomarker stn","probabilities":1.0,"Title":"Verification Of Wfa-Sialylated Muc1 As A Sensitive Biliary Biomarker For Human Biliary Tract Cancer","Abstract":"Background: The diagnostic accuracy of biliary cytology is limited. A novel sandwich enzyme-linked immunosorbent assay that combined Wisteria floribunda agglutinin (WFA) and anti-sialylated mucin 1 (MUC1) monoclonal antibody to target bile samples was recently developed. This study was designed to verify the diagnostic accuracy of WFA-sialylated MUC1 as a sensitive biliary biomarker for human biliary tract cancer. \r\n\r\n Methods: Bile samples from 27 patients with benign disease and 174 patients with biliary tract cancer were analyzed. A receiver-operated characteristic curve analysis for biliary WFA-sialylated MUC1 and serum CA19-9 levels was performed to determine the cutoff value for the prediction of the presence of biliary tract cancer. \r\n\r\n Results: Biliary WFA-sialylated MUC1 levels were significantly higher in the biliary tract cancer group compared with the benign group (P < 0.001). The cutoff value of WFA-sialylated MUC1 for discriminating biliary tract cancer was 10.5. The sensitivity of WFA-sialylated MUC1 in discriminating biliary tract cancer was much higher (82.2 %) than that of cytology (23.6 %) when this cutoff value was used. The cutoff value of serum CA19-9 for discriminating biliary tract cancer was 38 IU/L in the same cohort. All patients with biliary WFA-sialylated MUC1 and serum CA19-9 above the cutoff values had biliary tract cancer, and no patient with benign disease was categorized in this group. \r\n\r\n Conclusions: Biliary WFA-sialylated MUC1 is a useful biomarker for the differentiation of biliary tract cancer. The sensitivity of WFA-sialylated MUC1 was clearly higher than that of biliary cytology. Further data collection is necessary to validate the clinical usefulness of this biomarker.","Source":"STN","category":"ANIMAL","training_data":"Verification Of Wfa-Sialylated Muc1 As A Sensitive Biliary Biomarker For Human Biliary Tract Cancer Background: The diagnostic accuracy of biliary cytology is limited. A novel sandwich enzyme-linked immunosorbent assay that combined Wisteria floribunda agglutinin (WFA) and anti-sialylated mucin 1 (MUC1) monoclonal antibody to target bile samples was recently developed. This study was designed to verify the diagnostic accuracy of WFA-sialylated MUC1 as a sensitive biliary biomarker for human biliary tract cancer. \r\n\r\n Methods: Bile samples from 27 patients with benign disease and 174 patients with biliary tract cancer were analyzed. A receiver-operated characteristic curve analysis for biliary WFA-sialylated MUC1 and serum CA19-9 levels was performed to determine the cutoff value for the prediction of the presence of biliary tract cancer. \r\n\r\n Results: Biliary WFA-sialylated MUC1 levels were significantly higher in the biliary tract cancer group compared with the benign group (P < 0.001). The cutoff value of WFA-sialylated MUC1 for discriminating biliary tract cancer was 10.5. The sensitivity of WFA-sialylated MUC1 in discriminating biliary tract cancer was much higher (82.2 %) than that of cytology (23.6 %) when this cutoff value was used. The cutoff value of serum CA19-9 for discriminating biliary tract cancer was 38 IU/L in the same cohort. All patients with biliary WFA-sialylated MUC1 and serum CA19-9 above the cutoff values had biliary tract cancer, and no patient with benign disease was categorized in this group. \r\n\r\n Conclusions: Biliary WFA-sialylated MUC1 is a useful biomarker for the differentiation of biliary tract cancer. The sensitivity of WFA-sialylated MUC1 was clearly higher than that of biliary cytology. Further data collection is necessary to validate the clinical usefulness of this biomarker. STN","prediction_labels":"ANIMAL"},{"cleaned":"gallbladder cancer past present uncertain future although gallbladder cancer gbc common malignancy biliary tract relatively low incidence confounding symptomatology result advanced disease time presentation contributing poor prognosis decreased survival associated disease therefore increasingly important understand pathogenesis risk factors allow earliest possible diagnosis date gallbladder cancer poorly understood compared malignancies still commonly discovered incidentally cholecystectomy moreover much known biliary neoplasms whole understanding clinical molecular nuances gbc separate disease process prove cornerstone development early intervention potential screening overall effective treatment strategies present work reviews current understanding pathogenesis diagnosis staging natural history gbc additional focus surgical treatment review current adjuvant therapies unresectable advanced disease well prognostic factors provide fertile ground development future studies hopefully improve treatment outcomes affect overall survival highly morbid poorly understood malignancy pubmed","probabilities":0.9799733,"Title":"Gallbladder cancer: past, present and an uncertain future","Abstract":"Although gallbladder cancer (GBC) is the most common malignancy of the biliary tract, its relatively low incidence and confounding symptomatology result in advanced disease at the time presentation, contributing to the poor prognosis and decreased survival associated with this disease. It is therefore increasingly important to understand its pathogenesis and risk factors to allow for the earliest possible diagnosis. To date, gallbladder cancer is poorly understood compared to other malignancies, and is still most commonly discovered incidentally after cholecystectomy. Moreover, while much is known about biliary neoplasms as a whole, understanding the clinical and molecular nuances of GBC as a separate disease process will prove a cornerstone in the development of early intervention, potential screening and overall more effective treatment strategies. The present work reviews the most current understanding of the pathogenesis, diagnosis, staging and natural history of GBC, with additional focus on surgical treatment. Further, review of current adjuvant therapies for unresectable and advanced disease as well as prognostic factors provide fertile ground for the development of future studies which will hopefully improve treatment outcomes and affect overall survival for this highly morbid, poorly understood malignancy.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder cancer: past, present and an uncertain future Although gallbladder cancer (GBC) is the most common malignancy of the biliary tract, its relatively low incidence and confounding symptomatology result in advanced disease at the time presentation, contributing to the poor prognosis and decreased survival associated with this disease. It is therefore increasingly important to understand its pathogenesis and risk factors to allow for the earliest possible diagnosis. To date, gallbladder cancer is poorly understood compared to other malignancies, and is still most commonly discovered incidentally after cholecystectomy. Moreover, while much is known about biliary neoplasms as a whole, understanding the clinical and molecular nuances of GBC as a separate disease process will prove a cornerstone in the development of early intervention, potential screening and overall more effective treatment strategies. The present work reviews the most current understanding of the pathogenesis, diagnosis, staging and natural history of GBC, with additional focus on surgical treatment. Further, review of current adjuvant therapies for unresectable and advanced disease as well as prognostic factors provide fertile ground for the development of future studies which will hopefully improve treatment outcomes and affect overall survival for this highly morbid, poorly understood malignancy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"correlation ldh serum levels clinical outcome advanced biliary tract cancer patients treated first line chemotherapy ldh may represent indirect marker neo angiogenesis worse prognosis many tumour types assessed correlation ldh clinical outcome biliary tract cancer btc patients treated first line chemotherapy overall 114 advanced btc patients treated first line gemcitabine cisplatin included patients divided two groups low vs high ldh according pre treatment ldh values patients also classified according pre post treatment variation ldh serum levels increased vs decreased median progression free survival pfs 5 0 2 6 months respectively patients low high pre treatment ldh levels p 0 0042 hr 0 56 95 ci 0 37 0 87 median overall survival os 7 7 5 6 months low vs high ldh p 0 324 hr 0 81 95 ci 0 54 1 24 dcr 71 vs 43 low vs high ldh p 0 002 38 patients decreased ldh values treatment pfs os respectively 6 2 12 1 months whereas 76 patients post treatment increased ldh levels pfs os respectively 3 0 5 1 months pfs p 0 0009 hr 0 49 95 ic 0 33 0 74 os p 0 0001 hr 0 42 95 ic 0 27 0 63 data seem suggest ldh serum level may predict clinical outcome btc patients receiving first line chemotherapy pubmed","probabilities":0.9799733,"Title":"The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy","Abstract":"LDH may represent an indirect marker of neo-angiogenesis and worse prognosis in many tumour types. We assessed the correlation between LDH and clinical outcome for biliary tract cancer (BTC) patients treated with first-line chemotherapy. Overall, 114 advanced BTC patients treated with first-line gemcitabine and cisplatin were included. Patients were divided into two groups (low vs. high LDH), according to pre-treatment LDH values. Patients were also classified according to pre- and post-treatment variation in LDH serum levels (increased vs. decreased). Median progression free survival (PFS) was 5.0 and 2.6 months respectively in patients with low and high pre-treatment LDH levels (p = 0.0042, HR = 0.56, 95% CI: 0.37-0.87). Median overall survival (OS) was 7.7 and 5.6 months (low vs. high LDH) (p = 0.324, HR = 0.81, 95% CI: 0.54-1.24). DCR was 71% vs. 43% (low vs. high LDH) (p = 0.002). In 38 patients with decreased LDH values after treatment, PFS and OS were respectively 6.2 and 12.1 months, whereas in 76 patients with post-treatment increased LDH levels, PFS and OS were respectively 3.0 and 5.1 months (PFS: p = 0.0009; HR = 0.49; 95% IC: 0.33-0.74; OS: p < 0.0001; HR = 0.42; 95% IC: 0.27-0.63). Our data seem to suggest that LDH serum level may predict clinical outcome in BTC patients receiving first-line chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"The correlation between LDH serum levels and clinical outcome in advanced biliary tract cancer patients treated with first line chemotherapy LDH may represent an indirect marker of neo-angiogenesis and worse prognosis in many tumour types. We assessed the correlation between LDH and clinical outcome for biliary tract cancer (BTC) patients treated with first-line chemotherapy. Overall, 114 advanced BTC patients treated with first-line gemcitabine and cisplatin were included. Patients were divided into two groups (low vs. high LDH), according to pre-treatment LDH values. Patients were also classified according to pre- and post-treatment variation in LDH serum levels (increased vs. decreased). Median progression free survival (PFS) was 5.0 and 2.6 months respectively in patients with low and high pre-treatment LDH levels (p = 0.0042, HR = 0.56, 95% CI: 0.37-0.87). Median overall survival (OS) was 7.7 and 5.6 months (low vs. high LDH) (p = 0.324, HR = 0.81, 95% CI: 0.54-1.24). DCR was 71% vs. 43% (low vs. high LDH) (p = 0.002). In 38 patients with decreased LDH values after treatment, PFS and OS were respectively 6.2 and 12.1 months, whereas in 76 patients with post-treatment increased LDH levels, PFS and OS were respectively 3.0 and 5.1 months (PFS: p = 0.0009; HR = 0.49; 95% IC: 0.33-0.74; OS: p < 0.0001; HR = 0.42; 95% IC: 0.27-0.63). Our data seem to suggest that LDH serum level may predict clinical outcome in BTC patients receiving first-line chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence mortality trends intrahepatic cholangiocarcinoma us untold story 50 years abstract available google scholar","probabilities":0.9799733,"Title":"Incidence And Mortality Trends Of Intrahepatic Cholangiocarcinoma In The Us; An Untold Story Of 50 Years","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Incidence And Mortality Trends Of Intrahepatic Cholangiocarcinoma In The Us; An Untold Story Of 50 Years Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"enbd associated decreased tumor dissemination compared ptbd perihilar cholangiocarcinoma background little known regarding risk tumor dissemination percutaneous biliary drainage used surgical resection perihilar cholangiocarcinoma phc aimed compare incidence tumor dissemination preoperative endoscopic nasobiliary drainage enbd percutaneous transhepatic biliary drainage ptbd phc methods data 208 consecutive patients underwent phc resection 2000 2013 retrospectively analyzed influence drainage type incidence tumor dissemination examined seventy six patients underwent enbd 37 87 underwent ptbd 42 45 underwent surgery without preoperative biliary drainage wd 22 results respective 2 5 year estimated cumulative incidences tumor dissemination enbd group 11 8 14 6 lower ptbd group 28 8 35 9 p 0 003 equivalent wd group 11 2 15 9 p ns ptbd hazard ratio hr vs enbd 2 80 independent risk factor postoperative tumor dissemination multivariate analysis 2 5 year disease specific survival rates higher enbd group 67 6 47 3 ptbd group 56 6 27 8 p 0 032 equivalent wd group 64 9 53 8 p ns however drainage type independent risk factor multivariate analysis disease specific survival conclusion patients phc associated risk postoperative tumor dissemination enbd group lower ptbd group equivalent wd group thus enbd ideal procedure preoperative biliary drainage pubmed","probabilities":0.9799733,"Title":"ENBD is Associated with Decreased Tumor Dissemination Compared to PTBD in Perihilar Cholangiocarcinoma","Abstract":"BACKGROUND: Little is known regarding the risk of tumor dissemination when percutaneous biliary drainage is used before surgical resection of perihilar cholangiocarcinoma (PHC). We aimed to compare the incidence of tumor dissemination after preoperative endoscopic nasobiliary drainage (ENBD) with that after percutaneous transhepatic biliary drainage (PTBD) for PHC. METHODS: Data from 208 consecutive patients who underwent PHC resection between 2000 and 2013 were retrospectively analyzed. The influence of drainage type on incidence of tumor dissemination was examined. Seventy-six patients underwent ENBD (37%), 87 underwent PTBD (42%), and 45 underwent surgery without preoperative biliary drainage (WD, 22%). RESULTS: The respective 2- and 5-year estimated cumulative incidences of tumor dissemination in the ENBD group (11.8/14.6%) were lower than in the PTBD group (28.8/35.9%, p = 0.003) and equivalent to that in the WD group (11.2/15.9%, p = NS). PTBD (hazard ratio [HR] vs. ENBD, 2.80) was an independent risk factor for postoperative tumor dissemination in the multivariate analysis. The 2- and 5-year disease-specific survival rates were higher in the ENBD group (67.6/47.3%) than in the PTBD group (56.6/27.8%, p = 0.032) and equivalent to that in the WD group (64.9/53.8%, p = NS). However, drainage type was not an independent risk factor in multivariate analysis of disease-specific survival. CONCLUSION: For patients with PHC, the associated risk of postoperative tumor dissemination in the ENBD group was lower than in the PTBD group and equivalent to that in the WD group. Thus, ENBD is the ideal procedure for preoperative biliary drainage.","Source":"PubMed","category":"HUMAN","training_data":"ENBD is Associated with Decreased Tumor Dissemination Compared to PTBD in Perihilar Cholangiocarcinoma BACKGROUND: Little is known regarding the risk of tumor dissemination when percutaneous biliary drainage is used before surgical resection of perihilar cholangiocarcinoma (PHC). We aimed to compare the incidence of tumor dissemination after preoperative endoscopic nasobiliary drainage (ENBD) with that after percutaneous transhepatic biliary drainage (PTBD) for PHC. METHODS: Data from 208 consecutive patients who underwent PHC resection between 2000 and 2013 were retrospectively analyzed. The influence of drainage type on incidence of tumor dissemination was examined. Seventy-six patients underwent ENBD (37%), 87 underwent PTBD (42%), and 45 underwent surgery without preoperative biliary drainage (WD, 22%). RESULTS: The respective 2- and 5-year estimated cumulative incidences of tumor dissemination in the ENBD group (11.8/14.6%) were lower than in the PTBD group (28.8/35.9%, p = 0.003) and equivalent to that in the WD group (11.2/15.9%, p = NS). PTBD (hazard ratio [HR] vs. ENBD, 2.80) was an independent risk factor for postoperative tumor dissemination in the multivariate analysis. The 2- and 5-year disease-specific survival rates were higher in the ENBD group (67.6/47.3%) than in the PTBD group (56.6/27.8%, p = 0.032) and equivalent to that in the WD group (64.9/53.8%, p = NS). However, drainage type was not an independent risk factor in multivariate analysis of disease-specific survival. CONCLUSION: For patients with PHC, the associated risk of postoperative tumor dissemination in the ENBD group was lower than in the PTBD group and equivalent to that in the WD group. Thus, ENBD is the ideal procedure for preoperative biliary drainage. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression interleukin 6 associated epithelial mesenchymal transition survival rates gallbladder cancer present study aimed investigate expression interleukin 6 il 6 gallbladder cancer gbc tissues correlation survival rate association il 6 epithelial mesenchymal transition emt associated markers also examined using immunohistochemistry reverse transcription quantitative polymerase chain reaction rt qpcr western blot analysis protein mrna expression levels il 6 twist e cadherin vimentin 20 gbc tissues analyzed il 6 twist vimentin proteins overexpressed 40 20 70 human gbc samples respectively protein expression e cadherin higher 5 gbc samples differences significant p 0 05 western blot analysis also revealed overexpression il 6 twist vimentin underexpression e cadherin gbc samples poor differentiation local invasion higher tumor node metastasis tnm stage p 0 05 higher mrna expression levels il 6 twist vimentin reduced expression level e cadherin also demonstrated gbc tissues p 0 05 degree differentiation local invasion lymph node metastasis clinical stage significantly associated mrna expression levels il 6 twist e cadherin increased expression levels il 6 twist reduced expression e cadherin correlated shorter median survival rates p 0 05 line regression results revealed correlation among mrna expression levels il 6 twist e cadherin vimentin best knowledge present study first demonstrate il 6 associated emt associated markers tumor differentiation local invasion tnm stage survival rates gbc stn","probabilities":1.0,"Title":"Expression Of Interleukin-6 Is Associated With Epithelial-Mesenchymal Transition And Survival Rates In Gallbladder Cancer","Abstract":"The present study aimed to investigate the expression of interleukin‑6 (IL‑6) in gallbladder cancer (GBC) tissues and its correlation with survival rate. The association between IL‑6 and epithelial‑mesenchymal transition (EMT)‑associated markers was also examined. Using immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis, the protein and mRNA expression levels of IL‑6, Twist, E‑cadherin and Vimentin in 20 GBC tissues were analyzed. The IL‑6, Twist and Vimentin proteins were overexpressed in 40, 20 and 70% of the human GBC samples, respectively. The protein expression of E‑cadherin was higher in only 5% of the GBC samples. These differences were significant (P<0.05). Western blot analysis also revealed overexpression of IL‑6, Twist and Vimentin and underexpression of E‑cadherin in the GBC samples with poor differentiation, local invasion and a higher tumor‑node‑metastasis (TNM) stage (P<0.05). Higher mRNA expression levels of IL‑6, Twist and Vimentin and a reduced expression level of E‑cadherin were also demonstrated in the GBC tissues (P<0.05). The degree of differentiation, local invasion, lymph node metastasis and clinical stage were significantly associated with the mRNA expression levels of IL‑6, Twist and E‑cadherin. The increased expression levels of IL‑6 and Twist and the reduced expression of E‑cadherin correlated with shorter median survival rates (P<0.05). Line regression results revealed correlation among the mRNA expression levels of IL‑6, Twist, E‑cadherin and Vimentin. To the best of our knowledge, the present study is the first to demonstrate that IL‑6 is associated with EMT‑associated markers, tumor differentiation, local invasion, TNM stage and survival rates in GBC.","Source":"STN","category":"ANIMAL","training_data":"Expression Of Interleukin-6 Is Associated With Epithelial-Mesenchymal Transition And Survival Rates In Gallbladder Cancer The present study aimed to investigate the expression of interleukin‑6 (IL‑6) in gallbladder cancer (GBC) tissues and its correlation with survival rate. The association between IL‑6 and epithelial‑mesenchymal transition (EMT)‑associated markers was also examined. Using immunohistochemistry, reverse transcription quantitative polymerase chain reaction (RT‑qPCR) and western blot analysis, the protein and mRNA expression levels of IL‑6, Twist, E‑cadherin and Vimentin in 20 GBC tissues were analyzed. The IL‑6, Twist and Vimentin proteins were overexpressed in 40, 20 and 70% of the human GBC samples, respectively. The protein expression of E‑cadherin was higher in only 5% of the GBC samples. These differences were significant (P<0.05). Western blot analysis also revealed overexpression of IL‑6, Twist and Vimentin and underexpression of E‑cadherin in the GBC samples with poor differentiation, local invasion and a higher tumor‑node‑metastasis (TNM) stage (P<0.05). Higher mRNA expression levels of IL‑6, Twist and Vimentin and a reduced expression level of E‑cadherin were also demonstrated in the GBC tissues (P<0.05). The degree of differentiation, local invasion, lymph node metastasis and clinical stage were significantly associated with the mRNA expression levels of IL‑6, Twist and E‑cadherin. The increased expression levels of IL‑6 and Twist and the reduced expression of E‑cadherin correlated with shorter median survival rates (P<0.05). Line regression results revealed correlation among the mRNA expression levels of IL‑6, Twist, E‑cadherin and Vimentin. To the best of our knowledge, the present study is the first to demonstrate that IL‑6 is associated with EMT‑associated markers, tumor differentiation, local invasion, TNM stage and survival rates in GBC. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic implications estrogen receptor 1 vascular endothelial growth factor expression primary gallbladder carcinoma aim investigate prognostic significance estrogen receptor 1 er1 vascular endothelial growth factor vegf expression primary gallbladder carcinoma gbc identify new prognostic markers malignancy methods using immunohistochemistry investigated er1 vegf expression 78 gbc 78 cholelithiasis cs tissues results correlated clinicopathological features univariate multivariate analyses performed evaluate relationship er1 vegf expression patients prognosis kaplan meier survival analysis also performed results er1 vegf expression significantly higher gbc compared cs 47 78 vs 28 78 p 0 05 51 78 vs 33 78 p 0 05 er1 expression correlated gender p 0 05 vegf expression correlated tumor differentiation gbc patients p 0 05 univariate analysis age tumor node metastasis tnm stage factors associated gbc prognosis p 0 05 although statistical difference expression er1 vegf overall survival high expression er1 combined vegf predicted poor prognosis gbc patients 16 30 1 87 vs 24 97 2 09 log rank p 0 05 multivariate analysis combined expression er1 vegf tnm stage independent prognostic factors gbc patients p 0 05 conclusion combined expression er1 vegf potential prognostic marker gbc patients clinical detection er1 vegf surgically resected gbc tissues provide important reference decision making postoperative treatment programs pubmed","probabilities":0.7777778,"Title":"Prognostic implications of estrogen receptor 1 and vascular endothelial growth factor A expression in primary gallbladder carcinoma","Abstract":"AIM: To investigate the prognostic significance of estrogen receptor 1 (ER1) and vascular endothelial growth factor A (VEGF-A) expression in primary gallbladder carcinoma (GBC) to identify new prognostic markers for this malignancy. METHODS: Using immunohistochemistry, we investigated ER1 and VEGF-A expression in 78 GBC and 78 cholelithiasis (CS) tissues. The results were correlated with clinicopathological features. Univariate and multivariate analyses were performed to evaluate the relationship between ER1 and VEGF-A expression and patients' prognosis. Further Kaplan-Meier survival analysis was also performed. RESULTS: ER1 and VEGF-A expression was significantly higher in GBC compared with CS (47/78 vs 28/78, P<0.05; 51/78 vs 33/78, P<0.05). ER1 expression was correlated with gender (P<0.05) and VEGF-A expression was correlated with tumor differentiation in GBC patients (P<0.05). In univariate analysis, age and tumor node metastasis (TNM) stage were factors associated with GBC prognosis (P<0.05). Although there was no statistical difference between the expression of ER1 or VEGF-A and overall survival, the high expression of ER1 combined with VEGF-A predicted a poor prognosis for GBC patients (16.30±1.87 vs 24.97±2.09, log-rank P<0.05). In multivariate analysis, combined expression of ER1 and VEGF-A and TNM stage were independent prognostic factors for GBC patients (P<0.05). CONCLUSION: Combined expression of ER1 and VEGF-A is a potential prognostic marker for GBC patients. Clinical detection of ER1 and VEGF-A in surgically resected GBC tissues would provide an important reference for decision-making of postoperative treatment programs.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic implications of estrogen receptor 1 and vascular endothelial growth factor A expression in primary gallbladder carcinoma AIM: To investigate the prognostic significance of estrogen receptor 1 (ER1) and vascular endothelial growth factor A (VEGF-A) expression in primary gallbladder carcinoma (GBC) to identify new prognostic markers for this malignancy. METHODS: Using immunohistochemistry, we investigated ER1 and VEGF-A expression in 78 GBC and 78 cholelithiasis (CS) tissues. The results were correlated with clinicopathological features. Univariate and multivariate analyses were performed to evaluate the relationship between ER1 and VEGF-A expression and patients' prognosis. Further Kaplan-Meier survival analysis was also performed. RESULTS: ER1 and VEGF-A expression was significantly higher in GBC compared with CS (47/78 vs 28/78, P<0.05; 51/78 vs 33/78, P<0.05). ER1 expression was correlated with gender (P<0.05) and VEGF-A expression was correlated with tumor differentiation in GBC patients (P<0.05). In univariate analysis, age and tumor node metastasis (TNM) stage were factors associated with GBC prognosis (P<0.05). Although there was no statistical difference between the expression of ER1 or VEGF-A and overall survival, the high expression of ER1 combined with VEGF-A predicted a poor prognosis for GBC patients (16.30±1.87 vs 24.97±2.09, log-rank P<0.05). In multivariate analysis, combined expression of ER1 and VEGF-A and TNM stage were independent prognostic factors for GBC patients (P<0.05). CONCLUSION: Combined expression of ER1 and VEGF-A is a potential prognostic marker for GBC patients. Clinical detection of ER1 and VEGF-A in surgically resected GBC tissues would provide an important reference for decision-making of postoperative treatment programs. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"endoscopic management occluded biliary uncovered metal stents multicenter experience aim compare diverse endoscopic interventions management occluded uncovered self expanding metal stents semss placed palliative treatment unresectable malignant biliary obstruction methods retrospective review undertaken 4 tertiary endoscopic centers determine optimal management different types occluded semss technical success performed treatment occluded semss patency stent need re intervention financial costs treatment analyzed results fifty four patients included analysis 21 received hanaro 19 wallstent 14 flexus relief obstruction plastic stent inserted 24 patients second sems 25 mechanical cleaning performed 5 patients overall median second patency rates second semss plastic stents differ 133 d semss vs 106 d plastic stents p 0 856 similarly difference found overall survival sems plastic stent groups procedure related complications occurred incremental cost analysis showed successive plastic stenting cost saving strategy least greece conclusion insertion uncovered semss plastic stents safe effective treatment occluded uncovered semss insertion plastic stents appears cost effective strategy pubmed","probabilities":0.9799733,"Title":"Endoscopic management of occluded biliary uncovered metal stents: a multicenter experience","Abstract":"AIM: To compare diverse endoscopic interventions in the management of occluded uncovered self-expanding metal stents (SEMSs) that had been placed for palliative treatment of unresectable malignant biliary obstruction. METHODS: A retrospective review was undertaken in 4 tertiary endoscopic centers to determine optimal management of different types of occluded SEMSs. The technical success of performed treatment in occluded SEMSs, the patency of the stent, the need for re-intervention and the financial costs of each treatment were analyzed. RESULTS: Fifty four patients were included in the analysis; 21 received Hanaro, 19 Wallstent and 14 Flexus. For the relief of obstruction, a plastic stent was inserted in 24 patients, a second SEMS in 25 and mechanical cleaning was performed in 5 patients. The overall median second patency rates between second SEMSs and plastic stents did not differ (133 d for SEMSs vs 106 d for plastic stents; P=0.856). Similarly, no difference was found between the overall survival of SEMS and plastic stent groups, and no procedure-related complications occurred. Incremental cost analysis showed that successive plastic stenting was a cost-saving strategy at least in Greece. CONCLUSION: Insertion of uncovered SEMSs or plastic stents is a safe and effective treatment for occluded uncovered SEMSs; insertion of plastic stents appears to be the most cost-effective strategy.","Source":"PubMed","category":"HUMAN","training_data":"Endoscopic management of occluded biliary uncovered metal stents: a multicenter experience AIM: To compare diverse endoscopic interventions in the management of occluded uncovered self-expanding metal stents (SEMSs) that had been placed for palliative treatment of unresectable malignant biliary obstruction. METHODS: A retrospective review was undertaken in 4 tertiary endoscopic centers to determine optimal management of different types of occluded SEMSs. The technical success of performed treatment in occluded SEMSs, the patency of the stent, the need for re-intervention and the financial costs of each treatment were analyzed. RESULTS: Fifty four patients were included in the analysis; 21 received Hanaro, 19 Wallstent and 14 Flexus. For the relief of obstruction, a plastic stent was inserted in 24 patients, a second SEMS in 25 and mechanical cleaning was performed in 5 patients. The overall median second patency rates between second SEMSs and plastic stents did not differ (133 d for SEMSs vs 106 d for plastic stents; P=0.856). Similarly, no difference was found between the overall survival of SEMS and plastic stent groups, and no procedure-related complications occurred. Incremental cost analysis showed that successive plastic stenting was a cost-saving strategy at least in Greece. CONCLUSION: Insertion of uncovered SEMSs or plastic stents is a safe and effective treatment for occluded uncovered SEMSs; insertion of plastic stents appears to be the most cost-effective strategy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"concurrent chemoradiotherapy curatively resected gallbladder carcinoma propensity score matched analysis purpose compare overall survival os patients receiving radical resection followed concurrent chemoradiotherapy ccrt patients receiving radical resection advanced resectable gallbladder carcinoma gbc methods materials ninety four gbc patients stage pt2 4 n0 1 m0 consented inclusion clinical database june 2003 july 2013 patients received ccrt matched propensity score received nearest neighbor matching caliper width 0 2 ensure similar baseline characteristics group effects ccrt os disease free survival dfs evaluated kaplan meier analysis cox proportional hazards regression performed entire cohort adverse effects oncologic outcomes assessed results seventy eight patients gbc 39 ccrt 39 matched according propensity score 1 year 3 year 5 year os 74 4 56 4 42 4 ccrt group 51 3 30 8 17 9 group median survival time 27 months interquartile range iqr 12 58 months ccrt group versus 13 months iqr 5 30 months group p 004 1 year 3 year dfs 59 0 versus 35 9 48 7 versus 13 5 respectively median dfs 23 months iqr 8 57 months versus 7 months iqr 4 23 months p 004 conclusions os matched patients stage ii iva gbc significantly improved ccrt radiation therapy combined single agent dual agent chemotherapy feasible well tolerated pubmed","probabilities":0.9799733,"Title":"Concurrent Chemoradiotherapy in Curatively Resected Gallbladder Carcinoma: A Propensity Score-Matched Analysis","Abstract":"PURPOSE: To compare overall survival (OS) between patients receiving radical resection followed by concurrent chemoradiotherapy (S+CCRT) and patients receiving radical resection only (S) for advanced resectable gallbladder carcinoma (GBC). METHODS AND MATERIALS: Ninety-four GBC patients with stage pT2-4, N0-1, and M0 consented to inclusion in a clinical database from June 2003 to July 2013. Patients who received S+CCRT were matched by propensity score with those who received S through nearest-neighbor matching, with a caliper width of 0.2 to ensure similar baseline characteristics between each group. The effects of CCRT on OS and disease-free survival (DFS) were evaluated with Kaplan-Meier analysis. Cox proportional hazards regression was performed on the entire cohort. Adverse effects and oncologic outcomes were assessed. RESULTS: Seventy-eight patients with GBC (39 S+CCRT; 39 S) were matched according to propensity score; the 1-year, 3-year, and 5-year OS was 74.4%, 56.4%, and 42.4% for the S+CCRT group and 51.3%, 30.8%, and 17.9% for the S group. The median survival time was 27 months (interquartile range [IQR], 12-58 months) for the S+CCRT group versus 13 months (IQR, 5-30 months) for the S group (P=.004), with the 1-year and 3-year DFS being 59.0% versus 35.9% and 48.7% versus 13.5%, respectively, and the median DFS being 23 months (IQR, 8-57 months) versus 7 months (IQR, 4-23 months) (P=.004). CONCLUSIONS: The OS of matched patients with stage II-IVA GBC is significantly improved by CCRT. Radiation therapy combined with single-agent or dual-agent chemotherapy was feasible and well tolerated.","Source":"PubMed","category":"HUMAN","training_data":"Concurrent Chemoradiotherapy in Curatively Resected Gallbladder Carcinoma: A Propensity Score-Matched Analysis PURPOSE: To compare overall survival (OS) between patients receiving radical resection followed by concurrent chemoradiotherapy (S+CCRT) and patients receiving radical resection only (S) for advanced resectable gallbladder carcinoma (GBC). METHODS AND MATERIALS: Ninety-four GBC patients with stage pT2-4, N0-1, and M0 consented to inclusion in a clinical database from June 2003 to July 2013. Patients who received S+CCRT were matched by propensity score with those who received S through nearest-neighbor matching, with a caliper width of 0.2 to ensure similar baseline characteristics between each group. The effects of CCRT on OS and disease-free survival (DFS) were evaluated with Kaplan-Meier analysis. Cox proportional hazards regression was performed on the entire cohort. Adverse effects and oncologic outcomes were assessed. RESULTS: Seventy-eight patients with GBC (39 S+CCRT; 39 S) were matched according to propensity score; the 1-year, 3-year, and 5-year OS was 74.4%, 56.4%, and 42.4% for the S+CCRT group and 51.3%, 30.8%, and 17.9% for the S group. The median survival time was 27 months (interquartile range [IQR], 12-58 months) for the S+CCRT group versus 13 months (IQR, 5-30 months) for the S group (P=.004), with the 1-year and 3-year DFS being 59.0% versus 35.9% and 48.7% versus 13.5%, respectively, and the median DFS being 23 months (IQR, 8-57 months) versus 7 months (IQR, 4-23 months) (P=.004). CONCLUSIONS: The OS of matched patients with stage II-IVA GBC is significantly improved by CCRT. Radiation therapy combined with single-agent or dual-agent chemotherapy was feasible and well tolerated. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prevalence risk factors survival patients intrahepatic cholangiocarcinoma purpose investigate prevalence related risk factors survival intrahepatic cholangiocarcinoma mexican population material methods conducted cross sectional study medica sur hospital mexico city approval local research ethics committee found cases reviewing clinical records inpatients october 2005 january 2016 diagnosed malignant liver tumors clinical characteristics comorbidities obtained evaluate probable risk factors charlson index cases staged based tnm staging system bile duct tumors used american joint committee cancer median patient survival rates calculated using kaplan meier method results reviewed 233 cases hepatic cancer amongst hepatocellular carcinomas represented 19 3 n 45 followed intrahepatic cholangiocarcinomas accounted 7 7 n 18 median age patients intrahepatic cholangiocarcinoma 63 years presented cholestasis intrahepatic biliary ductal dilation unfortunately 89 n 16 advanced stage 80 multicentric tumors median survival 286 days among patients advanced stage tumors 25th 75th interquartile range 174 645 days correlation found presence comorbidities defined charlson index survival evaluated presence definite probable risk factors development intrahepatic cholangiocarcinoma smoking alcohol consumption primary sclerosing cholangitis discussion found overall prevalence intrahepatic cholangiocarcinoma 7 7 unfortunately patients diagnosed advanced stages smoking primary sclerosing cholangitis positive risk factors development population google scholar","probabilities":0.9799733,"Title":"Prevalence Risk Factors And Survival Of Patients With Intrahepatic Cholangiocarcinoma","Abstract":"Purpose\nTo investigate the prevalence, related risk factors, and survival of intrahepatic cholangiocarcinoma in a Mexican population.\nMaterial and methods\nWe conducted a cross-sectional study at Medica Sur Hospital in Mexico City with approval of the local research ethics committee. We found cases by reviewing all clinical records of inpatients between October 2005 and January 2016 who had been diagnosed with malignant liver tumors. Clinical characteristics and comorbidities were obtained to evaluate the probable risk factors and the Charlson index. The cases were staged based on the TNM staging system for bile duct tumors used by the American Joint Committee on Cancer and median patient survival rates were calculated using the Kaplan-Meier method.\nResults\nWe reviewed 233 cases of hepatic cancer. Amongst these, hepatocellular carcinomas represented 19.3% (n = 45), followed by intrahepatic cholangiocarcinomas, which accounted for 7.7% (n = 18). The median age of patients with intrahepatic cholangiocarcinoma was 63 years, and most of them presented with cholestasis and intrahepatic biliary ductal dilation. Unfortunately, 89% (n = 16) of them were in an advanced stage and 80% had multicentric tumors. Median survival was 286 days among patients with advanced stage tumors (25th-75th interquartile range, 174-645 days). No correlation was found between the presence of comorbidities defined by the Charlson index, and survival. We evaluated the presence of definite and probable risk factors for the development of intrahepatic cholangiocarcinoma, that is, smoking, alcohol consumption, and primary sclerosing cholangitis.\nDiscussion\nWe found an overall prevalence of intrahepatic cholangiocarcinoma of 7.7%; unfortunately, these patients were diagnosed at advanced stages. Smoking and primary sclerosing cholangitis were the positive risk factors for its development in this population.","Source":"Google Scholar","category":"HUMAN","training_data":"Prevalence Risk Factors And Survival Of Patients With Intrahepatic Cholangiocarcinoma Purpose\nTo investigate the prevalence, related risk factors, and survival of intrahepatic cholangiocarcinoma in a Mexican population.\nMaterial and methods\nWe conducted a cross-sectional study at Medica Sur Hospital in Mexico City with approval of the local research ethics committee. We found cases by reviewing all clinical records of inpatients between October 2005 and January 2016 who had been diagnosed with malignant liver tumors. Clinical characteristics and comorbidities were obtained to evaluate the probable risk factors and the Charlson index. The cases were staged based on the TNM staging system for bile duct tumors used by the American Joint Committee on Cancer and median patient survival rates were calculated using the Kaplan-Meier method.\nResults\nWe reviewed 233 cases of hepatic cancer. Amongst these, hepatocellular carcinomas represented 19.3% (n = 45), followed by intrahepatic cholangiocarcinomas, which accounted for 7.7% (n = 18). The median age of patients with intrahepatic cholangiocarcinoma was 63 years, and most of them presented with cholestasis and intrahepatic biliary ductal dilation. Unfortunately, 89% (n = 16) of them were in an advanced stage and 80% had multicentric tumors. Median survival was 286 days among patients with advanced stage tumors (25th-75th interquartile range, 174-645 days). No correlation was found between the presence of comorbidities defined by the Charlson index, and survival. We evaluated the presence of definite and probable risk factors for the development of intrahepatic cholangiocarcinoma, that is, smoking, alcohol consumption, and primary sclerosing cholangitis.\nDiscussion\nWe found an overall prevalence of intrahepatic cholangiocarcinoma of 7.7%; unfortunately, these patients were diagnosed at advanced stages. Smoking and primary sclerosing cholangitis were the positive risk factors for its development in this population. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"development theranostic convergence bioradiopharmaceutical immuno pet based radioimmunotherapy l1cam cholangiocarcinoma model purpose cholangiocarcinoma malignancy bile duct poor prognosis conventional chemotherapy radiotherapy generally ineffective surgical resection curative treatment cholangiocarcinoma l1 cell adhesion molecule l1cam known novel prognostic marker therapeutic target cholangiocarcinoma study aimed evaluate feasibility immuno pet imaging based radioimmunotherapy using radiolabeled anti l1cam antibody cholangiocarcinoma xenograft model experimental design prepared theranostic convergence bioradiopharmaceutical using chimeric anti l1cam antibody ca10 a3 conjugated 1 4 7 triazacyclononane 1 4 7 triacetic acid nota chelator labeled 64cu 177lu evaluated immuno pet spect ct imaging biodistribution 64cu 177lu ca10 a3 various cholangiocarcinoma xenograft models therapeutic efficacy response monitoring performed 177lu ca10 a3 18f fdg pet respectively immunohistochemistry done tunel ki 67 results radiolabeled ca10 a3 antibodies specifically recognized l1cam vitro clearly visualized cholangiocarcinoma tumors immuno pet spect ct imaging differentiated l1cam expression level cholangiocarcinoma xenograft models 177lu ca10 a3 12 95 mbq 100 g showed statistically significant reduction tumor volumes p 0 05 decreased glucose metabolism p 0 01 ihc analysis revealed 177lu ca10 a3 treatment increased tunel positive decreased ki 67 positive cells compared saline ca10 a3 177lu isotype conclusions anti l1cam immuno pet imaging using 64cu ca10 a3 translated clinic characterizing pharmacokinetics selecting appropriate patients radioimmunotherapy radioimmunotherapy using 177lu ca10 a3 may provide survival benefit l1cam expressing cholangiocarcinoma tumor theranostic convergence bioradiopharmaceutical strategy applied imaging biomarker based personalized medicine l1cam expressing patients cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Development Of A Theranostic Convergence Bioradiopharmaceutical For Immuno-Pet Based Radioimmunotherapy Of L1Cam In Cholangiocarcinoma Model","Abstract":"Purpose: Cholangiocarcinoma is a malignancy of bile duct with a poor prognosis. Conventional chemotherapy and radiotherapy are generally ineffective, and surgical resection is the only curative treatment for cholangiocarcinoma. L1-cell adhesion molecule (L1CAM) has been known as a novel prognostic marker and therapeutic target for cholangiocarcinoma. This study aimed to evaluate the feasibility of immuno-PET imaging-based radioimmunotherapy using radiolabeled anti-L1CAM antibody in cholangiocarcinoma xenograft model. \r\n\r\n Experimental design: We prepared a theranostic convergence bioradiopharmaceutical using chimeric anti-L1CAM antibody (cA10-A3) conjugated with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelator and labeled with 64Cu or 177Lu and evaluated the immuno-PET or SPECT/CT imaging and biodistribution with 64Cu-/177Lu-cA10-A3 in various cholangiocarcinoma xenograft models. Therapeutic efficacy and response monitoring were performed by 177Lu-cA10-A3 and 18F-FDG-PET, respectively, and immunohistochemistry was done by TUNEL and Ki-67. \r\n\r\n Results: Radiolabeled cA10-A3 antibodies specifically recognized L1CAM in vitro, clearly visualized cholangiocarcinoma tumors in immuno-PET and SPECT/CT imaging, and differentiated the L1CAM expression level in cholangiocarcinoma xenograft models. 177Lu-cA10-A3 (12.95 MBq/100 μg) showed statistically significant reduction in tumor volumes (P < 0.05) and decreased glucose metabolism (P < 0.01). IHC analysis revealed 177Lu-cA10-A3 treatment increased TUNEL-positive and decreased Ki-67-positive cells, compared with saline, cA10-A3, or 177Lu-isotype. \r\n\r\n Conclusions: Anti-L1CAM immuno-PET imaging using 64Cu-cA10-A3 could be translated into the clinic for characterizing the pharmacokinetics and selecting appropriate patients for radioimmunotherapy. Radioimmunotherapy using 177Lu-cA10-A3 may provide survival benefit in L1CAM-expressing cholangiocarcinoma tumor. Theranostic convergence bioradiopharmaceutical strategy would be applied as imaging biomarker-based personalized medicine in L1CAM-expressing patients with cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Development Of A Theranostic Convergence Bioradiopharmaceutical For Immuno-Pet Based Radioimmunotherapy Of L1Cam In Cholangiocarcinoma Model Purpose: Cholangiocarcinoma is a malignancy of bile duct with a poor prognosis. Conventional chemotherapy and radiotherapy are generally ineffective, and surgical resection is the only curative treatment for cholangiocarcinoma. L1-cell adhesion molecule (L1CAM) has been known as a novel prognostic marker and therapeutic target for cholangiocarcinoma. This study aimed to evaluate the feasibility of immuno-PET imaging-based radioimmunotherapy using radiolabeled anti-L1CAM antibody in cholangiocarcinoma xenograft model. \r\n\r\n Experimental design: We prepared a theranostic convergence bioradiopharmaceutical using chimeric anti-L1CAM antibody (cA10-A3) conjugated with 1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA) chelator and labeled with 64Cu or 177Lu and evaluated the immuno-PET or SPECT/CT imaging and biodistribution with 64Cu-/177Lu-cA10-A3 in various cholangiocarcinoma xenograft models. Therapeutic efficacy and response monitoring were performed by 177Lu-cA10-A3 and 18F-FDG-PET, respectively, and immunohistochemistry was done by TUNEL and Ki-67. \r\n\r\n Results: Radiolabeled cA10-A3 antibodies specifically recognized L1CAM in vitro, clearly visualized cholangiocarcinoma tumors in immuno-PET and SPECT/CT imaging, and differentiated the L1CAM expression level in cholangiocarcinoma xenograft models. 177Lu-cA10-A3 (12.95 MBq/100 μg) showed statistically significant reduction in tumor volumes (P < 0.05) and decreased glucose metabolism (P < 0.01). IHC analysis revealed 177Lu-cA10-A3 treatment increased TUNEL-positive and decreased Ki-67-positive cells, compared with saline, cA10-A3, or 177Lu-isotype. \r\n\r\n Conclusions: Anti-L1CAM immuno-PET imaging using 64Cu-cA10-A3 could be translated into the clinic for characterizing the pharmacokinetics and selecting appropriate patients for radioimmunotherapy. Radioimmunotherapy using 177Lu-cA10-A3 may provide survival benefit in L1CAM-expressing cholangiocarcinoma tumor. Theranostic convergence bioradiopharmaceutical strategy would be applied as imaging biomarker-based personalized medicine in L1CAM-expressing patients with cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"prediagnostic selenium status hepatobiliary cancer risk european prospective investigation cancer nutrition cohort background selenium status suboptimal many europeans may risk factor development various cancers including liver biliary tract objective wished examine whether selenium status advance cancer onset associated hepatobiliary cancers epic european prospective investigation cancer nutrition study design assessed prediagnostic selenium status measuring serum concentrations selenium selenoprotein p sepp major circulating selenium transfer protein examined association hepatocellular carcinoma hcc n 121 gallbladder biliary tract cancers gbtcs n 100 intrahepatic bile duct cancer ihbc n 40 risk nested case control design within epic study selenium measured total reflection x ray fluorescence sepp determined colorimetric sandwich elisa multivariable ors 95 cis calculated using conditional logistic regression results hcc gbtc cases ihbc cases showed significantly lower circulating selenium sepp concentrations matched controls higher circulating selenium associated significantly lower hcc risk per 20 g l increase 0 41 95 ci 0 23 0 72 risk gbtc ihbc similarly higher sepp concentrations associated lowered hcc risk categorical continuous analyses hcc p trend 0 0001 per 1 5 mg l increase 0 37 95 ci 0 21 0 63 conclusion findings large prospective cohort provide evidence suboptimal selenium status europeans may associated appreciably increased risk hcc development pubmed","probabilities":0.9799733,"Title":"Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort","Abstract":"BACKGROUND: Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. OBJECTIVE: We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. DESIGN: We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. RESULTS: HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-μg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). CONCLUSION: These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development.","Source":"PubMed","category":"HUMAN","training_data":"Prediagnostic selenium status and hepatobiliary cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort BACKGROUND: Selenium status is suboptimal in many Europeans and may be a risk factor for the development of various cancers, including those of the liver and biliary tract. OBJECTIVE: We wished to examine whether selenium status in advance of cancer onset is associated with hepatobiliary cancers in the EPIC (European Prospective Investigation into Cancer and Nutrition) study. DESIGN: We assessed prediagnostic selenium status by measuring serum concentrations of selenium and selenoprotein P (SePP; the major circulating selenium transfer protein) and examined the association with hepatocellular carcinoma (HCC; n = 121), gallbladder and biliary tract cancers (GBTCs; n = 100), and intrahepatic bile duct cancer (IHBC; n = 40) risk in a nested case-control design within the EPIC study. Selenium was measured by total reflection X-ray fluorescence, and SePP was determined by a colorimetric sandwich ELISA. Multivariable ORs and 95% CIs were calculated by using conditional logistic regression. RESULTS: HCC and GBTC cases, but not IHBC cases, showed significantly lower circulating selenium and SePP concentrations than their matched controls. Higher circulating selenium was associated with a significantly lower HCC risk (OR per 20-μg/L increase: 0.41; 95% CI: 0.23, 0.72) but not with the risk of GBTC or IHBC. Similarly, higher SePP concentrations were associated with lowered HCC risk only in both the categorical and continuous analyses (HCC: P-trend ≤ 0.0001; OR per 1.5-mg/L increase: 0.37; 95% CI: 0.21, 0.63). CONCLUSION: These findings from a large prospective cohort provide evidence that suboptimal selenium status in Europeans may be associated with an appreciably increased risk of HCC development. PubMed","prediction_labels":"HUMAN"},{"cleaned":"serum cyfra 21 1 biliary tract cancers reliable biomarker gallbladder carcinoma intrahepatic cholangiocarcinoma background biliary tract cancers encompass gallbladder carcinoma intrahepatic perihilar distal cholangiocarcinoma upregulated serum cyfra 21 1 reported intrahepatic cholangiocarcinoma aims present study aimed explore clinical significance serum cyfra 21 1 biliary tract cancer subtypes methods serum cyfra 21 1 carbohydrate antigen 19 9 carcinoembryonic antigen quantitated preoperatively postoperatively follow 134 malignant 52 benign patients receiver operator characteristic curves biomarkers analyzed level cyfra 21 1 correlated patients clinicopathological features follow data results cyfra 21 1 significantly upregulated biliary malignancies expressional difference existed subtypes based maximal youden index cutoff values selected ng ml 2 61 biliary tract cancers sensitivity 74 6 specificity 84 6 3 27 intrahepatic cholangiocarcinoma 75 6 96 2 gallbladder carcinoma 93 7 96 2 2 27 perihilar cholangiocarcinoma 71 0 71 2 2 61 distal cholangiocarcinoma 63 3 84 6 cyfra 21 1 showed better diagnostic performance biomarkers gallbladder carcinoma intrahepatic cholangiocarcinoma performance inferior combination three biomarkers declined curative resection re elevated tumor recurred correlated tumor aggressiveness tnm stage independent predictor 1 year recurrence free survival overall survival multivariate analysis conclusion serum cyfra 21 1 represents reliable biomarker gallbladder carcinoma intrahepatic cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Serum CYFRA 21-1 in Biliary Tract Cancers: A Reliable Biomarker for Gallbladder Carcinoma and Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: Biliary tract cancers encompass gallbladder carcinoma, and intrahepatic, perihilar and distal cholangiocarcinoma. Upregulated serum CYFRA 21-1 has been reported in intrahepatic cholangiocarcinoma. AIMS: The present study aimed to explore the clinical significance of serum CYFRA 21-1 in all biliary tract cancer subtypes. METHODS: Serum CYFRA 21-1, carbohydrate antigen 19-9 and carcinoembryonic antigen were quantitated preoperatively, postoperatively and during follow-up in 134 malignant and 52 benign patients. Receiver operator characteristic curves of biomarkers were analyzed. Level of CYFRA 21-1 was correlated with patients' clinicopathological features and follow-up data. RESULTS: CYFRA 21-1 was significantly upregulated in biliary malignancies, and expressional difference existed between these subtypes. Based on the maximal Youden's index, cutoff values were selected (ng/mL): 2.61 for biliary tract cancers (sensitivity 74.6 % and specificity 84.6 %); 3.27 for intrahepatic cholangiocarcinoma (75.6 and 96.2 %) and gallbladder carcinoma (93.7 and 96.2 %); 2.27 for perihilar cholangiocarcinoma (71.0 and 71.2 %); and 2.61 for distal cholangiocarcinoma (63.3 and 84.6 %). CYFRA 21-1 showed better diagnostic performance than other biomarkers in gallbladder carcinoma and intrahepatic cholangiocarcinoma; its performance was not inferior to that of the combination of these three biomarkers and declined after curative resection and re-elevated when tumor recurred, which was correlated with tumor aggressiveness and TNM stage; it was an independent predictor for 1-year recurrence-free survival and overall survival on multivariate analysis. CONCLUSION: Serum CYFRA 21-1 represents a reliable biomarker for gallbladder carcinoma and intrahepatic cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Serum CYFRA 21-1 in Biliary Tract Cancers: A Reliable Biomarker for Gallbladder Carcinoma and Intrahepatic Cholangiocarcinoma BACKGROUND: Biliary tract cancers encompass gallbladder carcinoma, and intrahepatic, perihilar and distal cholangiocarcinoma. Upregulated serum CYFRA 21-1 has been reported in intrahepatic cholangiocarcinoma. AIMS: The present study aimed to explore the clinical significance of serum CYFRA 21-1 in all biliary tract cancer subtypes. METHODS: Serum CYFRA 21-1, carbohydrate antigen 19-9 and carcinoembryonic antigen were quantitated preoperatively, postoperatively and during follow-up in 134 malignant and 52 benign patients. Receiver operator characteristic curves of biomarkers were analyzed. Level of CYFRA 21-1 was correlated with patients' clinicopathological features and follow-up data. RESULTS: CYFRA 21-1 was significantly upregulated in biliary malignancies, and expressional difference existed between these subtypes. Based on the maximal Youden's index, cutoff values were selected (ng/mL): 2.61 for biliary tract cancers (sensitivity 74.6 % and specificity 84.6 %); 3.27 for intrahepatic cholangiocarcinoma (75.6 and 96.2 %) and gallbladder carcinoma (93.7 and 96.2 %); 2.27 for perihilar cholangiocarcinoma (71.0 and 71.2 %); and 2.61 for distal cholangiocarcinoma (63.3 and 84.6 %). CYFRA 21-1 showed better diagnostic performance than other biomarkers in gallbladder carcinoma and intrahepatic cholangiocarcinoma; its performance was not inferior to that of the combination of these three biomarkers and declined after curative resection and re-elevated when tumor recurred, which was correlated with tumor aggressiveness and TNM stage; it was an independent predictor for 1-year recurrence-free survival and overall survival on multivariate analysis. CONCLUSION: Serum CYFRA 21-1 represents a reliable biomarker for gallbladder carcinoma and intrahepatic cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cisplatin gemcitabine oxaliplatin gemcitabine treatment advanced biliary tract cancer systematic review cisplatin gemcitabine association standard care first line regimen advanced biliary tract cancer nevertheless oxaliplatin gemcitabine regimen frequently preferred comparative effectiveness clinical outcomes cisplatin versus oxaliplatin containing chemotherapy available systematic review studies assessing cisplatin gemcitabine oxaliplatin gemcitabine chemotherapies advanced biliary tract cancer performed published studies evaluating cisplatin gemcitabine oxaliplatin gemcitabine advanced biliary tract cancer included study weighted according number patients included primary objective assess weighted median medians overall survival mos reported regimens secondary goals assess weighted median medians progression free survival mpfs toxic effects pooled compared within arm thirty three studies involving 1470 patients analyzed total 771 699 patients treated cisplatin gemcitabine oxaliplatin gemcitabine respectively weighted median mos 9 7 months cisplatin group 9 5 months oxaliplatin group cisplatin based chemotherapy significantly associated grade 3 4 asthenia diarrhea liver toxicity hematological toxicity sensitivity analysis including studies standard regimen cisplatin 25 35 mg m 2 administered days 1 8 showed weighted median mos increased 9 7 11 7 months gem cddp regimen remained toxic gemox regimen results suggest gem cddp regimen cisplatin 25 35 mg m 2 administered days 1 8 associated survival advantage gemox regimen addition toxicity pubmed","probabilities":0.9799733,"Title":"Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: a systematic review","Abstract":"Cisplatin/gemcitabine association has been a standard of care for first-line regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine regimen is frequently preferred. Because comparative effectiveness in clinical outcomes of cisplatin- versus oxaliplatin-containing chemotherapy is not available, a systematic review of studies assessing cisplatin/gemcitabine or oxaliplatin/gemcitabine chemotherapies in advanced biliary tract cancer was performed. Published studies evaluating cisplatin/gemcitabine or oxaliplatin/gemcitabine in advanced biliary tract cancer were included. Each study was weighted according to the number of patients included. The primary objective was to assess weighted median of medians overall survival (mOS) reported for both regimens. Secondary goals were to assess weighted median of medians progression-free survival (mPFS) and toxic effects were pooled and compared within each arm. Thirty-three studies involving 1470 patients were analyzed. In total, 771 and 699 patients were treated by cisplatin/gemcitabine and oxaliplatin/gemcitabine, respectively. Weighted median of mOS was 9.7 months in cisplatin group and 9.5 months in oxaliplatin group. Cisplatin-based chemotherapy was significantly associated with more grade 3 and 4 asthenia, diarrhea, liver toxicity, and hematological toxicity. Sensitivity analysis including only the studies with the standard regimen of cisplatin (25-35 mg/m(2) administered on days 1 and 8) showed that the weighted median of mOS increased from 9.7 to 11.7 months but Gem/CDDP regimen remained more toxic than Gemox regimen. These results suggest that the Gem/CDDP regimen with cisplatin (25-35 mg/m(2)) administered on days 1 and 8 is associated with survival advantage than Gemox regimen but with addition of toxicity.","Source":"PubMed","category":"HUMAN","training_data":"Cisplatin/gemcitabine or oxaliplatin/gemcitabine in the treatment of advanced biliary tract cancer: a systematic review Cisplatin/gemcitabine association has been a standard of care for first-line regimen in advanced biliary tract cancer nevertheless oxaliplatin/gemcitabine regimen is frequently preferred. Because comparative effectiveness in clinical outcomes of cisplatin- versus oxaliplatin-containing chemotherapy is not available, a systematic review of studies assessing cisplatin/gemcitabine or oxaliplatin/gemcitabine chemotherapies in advanced biliary tract cancer was performed. Published studies evaluating cisplatin/gemcitabine or oxaliplatin/gemcitabine in advanced biliary tract cancer were included. Each study was weighted according to the number of patients included. The primary objective was to assess weighted median of medians overall survival (mOS) reported for both regimens. Secondary goals were to assess weighted median of medians progression-free survival (mPFS) and toxic effects were pooled and compared within each arm. Thirty-three studies involving 1470 patients were analyzed. In total, 771 and 699 patients were treated by cisplatin/gemcitabine and oxaliplatin/gemcitabine, respectively. Weighted median of mOS was 9.7 months in cisplatin group and 9.5 months in oxaliplatin group. Cisplatin-based chemotherapy was significantly associated with more grade 3 and 4 asthenia, diarrhea, liver toxicity, and hematological toxicity. Sensitivity analysis including only the studies with the standard regimen of cisplatin (25-35 mg/m(2) administered on days 1 and 8) showed that the weighted median of mOS increased from 9.7 to 11.7 months but Gem/CDDP regimen remained more toxic than Gemox regimen. These results suggest that the Gem/CDDP regimen with cisplatin (25-35 mg/m(2)) administered on days 1 and 8 is associated with survival advantage than Gemox regimen but with addition of toxicity. PubMed","prediction_labels":"HUMAN"},{"cleaned":"postoperative mortality liver resection perihilar cholangiocarcinoma development risk score importance biliary drainage future liver remnant background liver surgery perihilar cholangiocarcinoma phc associated postoperative mortality ranging 5 18 aim study develop preoperative risk score postoperative mortality liver resection phc assess effect biliary drainage future liver remnant flr study design consecutive series 287 patients submitted major liver resection presumed phc 1997 2014 2 western centers analyzed 228 patients 79 underwent preoperative drainage jaundice future liver remnant volumes calculated ct volumetry completeness flr drainage assessed imaging logistic regression used develop mortality risk score results postoperative mortality 90 days 14 independently predicted age odds ratio per 10 years 2 1 preoperative cholangitis 4 1 flr volume 30 2 9 portal vein reconstruction 2 3 incomplete flr drainage patients flr volume 50 2 8 risk score showed good discrimination area curve 0 75 bootstrap validation ranking patients tertiles identified 3 ie low intermediate high risk subgroups predicted mortalities 2 11 37 postoperative mortality observed 33 undrained patients flr volumes 50 including 10 jaundiced patients median bilirubin level 11 mg dl conclusions mortality risk score patients resectable phc used patient counseling identification modifiable risk factors include flr volume flr drainage status preoperative cholangitis found evidence support preoperative biliary drainage patients flr volume 50 pubmed","probabilities":0.9799733,"Title":"Postoperative Mortality after Liver Resection for Perihilar Cholangiocarcinoma: Development of a Risk Score and Importance of Biliary Drainage of the Future Liver Remnant","Abstract":"BACKGROUND: Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR). STUDY DESIGN: A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score. RESULTS: Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio [OR] per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume <30% (OR = 2.9), portal vein reconstruction (OR = 2.3), and incomplete FLR drainage in patients with FLR volume <50% (OR = 2.8). The risk score showed good discrimination (area under the curve = 0.75 after bootstrap validation) and ranking patients in tertiles identified 3 (ie low, intermediate, and high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes >50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL). CONCLUSIONS: The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume >50%.","Source":"PubMed","category":"HUMAN","training_data":"Postoperative Mortality after Liver Resection for Perihilar Cholangiocarcinoma: Development of a Risk Score and Importance of Biliary Drainage of the Future Liver Remnant BACKGROUND: Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR). STUDY DESIGN: A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score. RESULTS: Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio [OR] per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume <30% (OR = 2.9), portal vein reconstruction (OR = 2.3), and incomplete FLR drainage in patients with FLR volume <50% (OR = 2.8). The risk score showed good discrimination (area under the curve = 0.75 after bootstrap validation) and ranking patients in tertiles identified 3 (ie low, intermediate, and high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes >50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL). CONCLUSIONS: The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume >50%. PubMed","prediction_labels":"HUMAN"},{"cleaned":"trends incidence management cancer ampulla vater aim provide trends incidence management survival cancer ampulla vater well defined french population methods data obtained population based digestive cancer registry burgundy 34 year period age standardized incidence rates computed using world standard population average annual variations incidence rates estimated using poisson regression univariate multivariate relative survival analysis performed results age standardized incidence rates 0 46 0 30 per 100000 inhabitants men women respectively incidence rate increased 0 26 1976 1984 0 58 2003 2009 men remained stable women resection cure performed 48 3 cases proportion stable study period among cases curative resection pancreatico duodenectomy performed 94 0 cases ampullectomy 6 0 cases total 50 8 cancers ampulla vater diagnosed advanced stage proportion remained stable throughout study period overall 1 5 year relative survival rates 60 2 27 7 respectively relative survival vary time treatment stage diagnosis important determinants survival 5 year relative survival rate 41 5 resection cure 9 5 palliative surgery 6 7 symptomatic treatment multivariate analysis stage diagnosis significantly influenced risk death conclusion cancer ampulla vater still uncommon incidence increased men burgundy diagnosis often made advanced stage dramatically worsening prognosis pubmed","probabilities":0.9799733,"Title":"Trends in incidence and management of cancer of the ampulla of Vater","Abstract":"AIM: To provide trends in incidence, management and survival of cancer of the ampulla of Vater in a well-defined French population. METHODS: Data were obtained from the population-based digestive cancer registry of Burgundy over a 34-year period. Age-standardized incidence rates were computed using the world standard population. Average annual variations in incidence rates were estimated using a poisson regression. A univariate and multivariate relative survival analysis was performed. RESULTS: Age-standardized incidence rates were 0.46 and 0.30 per 100000 inhabitants for men and women, respectively. Incidence rate increased from 0.26 (1976-1984) to 0.58 (2003-2009) for men and remained stable for women. Resection for cure was performed in 48.3% of cases. This proportion was stable over the study period. Among cases with curative resection, pancreatico-duodenectomy was performed in 94.0% of cases and ampullectomy in 6.0% of cases. A total of 50.8% of cancers of the ampulla of Vater were diagnosed at an advanced stage. Their proportion remained stable throughout the study period. The overall 1- and 5-year relative survival rates were 60.2% and 27.7%, respectively. Relative survival did not vary over time. Treatment and stage at diagnosis were the most important determinants of survival. The 5-year relative survival rate was 41.5% after resection for cure, 9.5% after palliative surgery and 6.7% after symptomatic treatment. In multivariate analysis, only stage at diagnosis significantly influenced the risk of death. CONCLUSION: Cancer of the ampulla of Vater is still uncommon, but its incidence increased for men in Burgundy. Diagnosis is often made at an advanced stage, dramatically worsening the prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Trends in incidence and management of cancer of the ampulla of Vater AIM: To provide trends in incidence, management and survival of cancer of the ampulla of Vater in a well-defined French population. METHODS: Data were obtained from the population-based digestive cancer registry of Burgundy over a 34-year period. Age-standardized incidence rates were computed using the world standard population. Average annual variations in incidence rates were estimated using a poisson regression. A univariate and multivariate relative survival analysis was performed. RESULTS: Age-standardized incidence rates were 0.46 and 0.30 per 100000 inhabitants for men and women, respectively. Incidence rate increased from 0.26 (1976-1984) to 0.58 (2003-2009) for men and remained stable for women. Resection for cure was performed in 48.3% of cases. This proportion was stable over the study period. Among cases with curative resection, pancreatico-duodenectomy was performed in 94.0% of cases and ampullectomy in 6.0% of cases. A total of 50.8% of cancers of the ampulla of Vater were diagnosed at an advanced stage. Their proportion remained stable throughout the study period. The overall 1- and 5-year relative survival rates were 60.2% and 27.7%, respectively. Relative survival did not vary over time. Treatment and stage at diagnosis were the most important determinants of survival. The 5-year relative survival rate was 41.5% after resection for cure, 9.5% after palliative surgery and 6.7% after symptomatic treatment. In multivariate analysis, only stage at diagnosis significantly influenced the risk of death. CONCLUSION: Cancer of the ampulla of Vater is still uncommon, but its incidence increased for men in Burgundy. Diagnosis is often made at an advanced stage, dramatically worsening the prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"obesity cancer risk evidence mechanisms recommendations obesity growing health problem worldwide associated metabolic syndrome diabetes cardiovascular disease hypertension chronic diseases recently obesity cancer link received much attention epidemiological studies shown obesity also associated increased risk several cancer types including colon breast endometrium liver kidney esophagus gastric pancreatic gallbladder leukemia also lead poorer treatment increased cancer related mortality biological mechanisms underlying relationship obesity cancer well understood include modulation energy balance calorie restriction growth factors multiple signaling pathways inflammatory processes key among signaling pathways linking obesity cancer pi3k akt mtor cascade target many obesity associated factors regulates cell proliferation survival understanding molecular cellular mechanisms obesity cancer connection important developing potential therapeutics link obesity cancer underscores recommendation maintain healthy body weight throughout life one important ways protect cancer pubmed","probabilities":0.962963,"Title":"Obesity and cancer risk: evidence, mechanisms, and recommendations","Abstract":"Obesity, a growing health problem worldwide, has been associated with the metabolic syndrome, diabetes, cardiovascular disease, hypertension, and other chronic diseases. Recently, the obesity-cancer link has received much attention. Epidemiological studies have shown that obesity is also associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment and increased cancer-related mortality. Biological mechanisms underlying the relationship between obesity and cancer are not well understood. They include modulation of energy balance and calorie restriction, growth factors, multiple signaling pathways, and inflammatory processes. Key among the signaling pathways linking obesity and cancer is the PI3K/Akt/mTOR cascade, which is a target of many of the obesity-associated factors and regulates cell proliferation and survival. Understanding the molecular and cellular mechanisms of the obesity-cancer connection is important in developing potential therapeutics. The link between obesity and cancer underscores the recommendation to maintain a healthy body weight throughout life as one of the most important ways to protect against cancer.","Source":"PubMed","category":"HUMAN","training_data":"Obesity and cancer risk: evidence, mechanisms, and recommendations Obesity, a growing health problem worldwide, has been associated with the metabolic syndrome, diabetes, cardiovascular disease, hypertension, and other chronic diseases. Recently, the obesity-cancer link has received much attention. Epidemiological studies have shown that obesity is also associated with increased risk of several cancer types, including colon, breast, endometrium, liver, kidney, esophagus, gastric, pancreatic, gallbladder, and leukemia, and can also lead to poorer treatment and increased cancer-related mortality. Biological mechanisms underlying the relationship between obesity and cancer are not well understood. They include modulation of energy balance and calorie restriction, growth factors, multiple signaling pathways, and inflammatory processes. Key among the signaling pathways linking obesity and cancer is the PI3K/Akt/mTOR cascade, which is a target of many of the obesity-associated factors and regulates cell proliferation and survival. Understanding the molecular and cellular mechanisms of the obesity-cancer connection is important in developing potential therapeutics. The link between obesity and cancer underscores the recommendation to maintain a healthy body weight throughout life as one of the most important ways to protect against cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental diagnosis gallbladder cancer vlc experience review literature aim incidental gallbladder cancer gbc frequent medical entity discovered specimen cholecystectomy benign disease aim value importance incidental diagnosis gallbladder cancer based experience methods data patients treated videolaparoscopic cholecystectomy vlc january 2000 december 2010 lithiasis retrospectively analyzed cases precautions taken reduce eventual cancer spreading endobag co2 drainage trocars avoidance gallbladder injuries results 2000 2010 318 patients underwent vlc preoperative us positive gallstones vlc realized patients rate conversion 0 3 patients 0 9 gbc incidentally discovered pathological exam specimen survival patients longer three years casual finding cancer vlc become frequent event 0 2 2 9 cases literature 0 9 personal experience good results obtained ptis pt1b general experience literature higher stages regardless comorbidities frequent old patients leaves less choice therapy conclusion incidental diagnosis gbc gives possibility treat earlier stage aggressive disease thus improving prognosis vlc patient gallstones risk factors abnormal biliary junction polyps 1 cm good way modify survival gbc google scholar","probabilities":0.9799733,"Title":"Incidental Diagnosis Of Gallbladder Cancer After Vlc: Our Experience And Review Of The Literature","Abstract":"Aim: Incidental gallbladder cancer (GBC) is a more and more frequent medical entity discovered on the specimen after a cholecystectomy for a benign disease. Our aim is to value the importance of incidental diagnosis of gallbladder cancer based on our experience.\nMethods: Data on patients treated with videolaparoscopic cholecystectomy (VLC) from January 2000 to December 2010 for lithiasis were retrospectively analyzed. In all cases all precautions were taken to reduce eventual cancer spreading (endobag, CO2 drainage through trocars and avoidance of gallbladder injuries).\nResults: From 2000 to 2010, 318 patients underwent to VLC after preoperative US positive for gallstones. VLC has been realized in all patients with a rate of conversion of 0%. In 3 of these patients (0.9%) the GBC was incidentally discovered during pathological exam of specimen, the survival for all patients has been longer than three years. The casual finding of cancer during VLC has become a frequent event, from 0.2 to 2.9% of cases in literature (0.9% in our personal experience). Good results were obtained for pTis and pT1b in general experience of the literature, while higher stages regardless comorbidities frequent in old patients, leaves less choice in therapy.\nConclusion: The incidental diagnosis of GBC gives the possibility to treat at an earlier stage a very aggressive disease, thus improving the prognosis, VLC in all patient with gallstones and other risk factors (abnormal biliary junction and polyps >1 cm) is a good way to modify the survival in GBC.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidental Diagnosis Of Gallbladder Cancer After Vlc: Our Experience And Review Of The Literature Aim: Incidental gallbladder cancer (GBC) is a more and more frequent medical entity discovered on the specimen after a cholecystectomy for a benign disease. Our aim is to value the importance of incidental diagnosis of gallbladder cancer based on our experience.\nMethods: Data on patients treated with videolaparoscopic cholecystectomy (VLC) from January 2000 to December 2010 for lithiasis were retrospectively analyzed. In all cases all precautions were taken to reduce eventual cancer spreading (endobag, CO2 drainage through trocars and avoidance of gallbladder injuries).\nResults: From 2000 to 2010, 318 patients underwent to VLC after preoperative US positive for gallstones. VLC has been realized in all patients with a rate of conversion of 0%. In 3 of these patients (0.9%) the GBC was incidentally discovered during pathological exam of specimen, the survival for all patients has been longer than three years. The casual finding of cancer during VLC has become a frequent event, from 0.2 to 2.9% of cases in literature (0.9% in our personal experience). Good results were obtained for pTis and pT1b in general experience of the literature, while higher stages regardless comorbidities frequent in old patients, leaves less choice in therapy.\nConclusion: The incidental diagnosis of GBC gives the possibility to treat at an earlier stage a very aggressive disease, thus improving the prognosis, VLC in all patient with gallstones and other risk factors (abnormal biliary junction and polyps >1 cm) is a good way to modify the survival in GBC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"effects claudin 1 downregulation physiologicaprocesses gallbladder cancer sgc996 cells gallbladder cancer high recurrence mortality rate limited treatment options therefore elucidating underlying molecular mechanisms disease beneficial achieve earlier diagnosis potentially identify novel treatment targets claudin 1 tight junction protein associated development prognosis several types cancer preliminary studies demonstrated claudin 1 expression elevated gallbladder cancer tissues therefore aim present study investigate effects downregulating claudin 1 physiological processes gallbladder cancer cells gallbladder cancer sgc996 cell line transfected claudin 1 rna interference lentivirus lv cldn1 rnai downregulate claudin 1 expression downstream effects cell proliferation cell cycle apoptosis cell invasion investigated following transfection lv cldn1 rnai results mtt assay revealed downregulating claudin 1 affect proliferation sgc996 cells however flow cytometry analysis demonstrated number cells arrested g1 phase increased significantly whereas amount cells arrested phase significantly reduced annexin v apc single color staining demonstrated downregulating claudin 1 expression increased ratio cell apoptosis confirmed results western blot analysis levels pro apoptotic b cell lymphoma 2 bcl 2 associated x protein anti apoptotic bcl 2 protein increased decreased respectively finally transwell assay indicated claudin 1 downregulation inhibited cell invasion overall results present study indicated downregulating claudin 1 expression promoted apoptosis gallbladder cancer cells inhibited cell invasion indicating claudin 1 may involved recurrence metastasis gallbladder cancer insights provide theoretical experimental foundations considering claudin 1 novel target treatment gallbladder cancer stn","probabilities":0.9467213,"Title":"Effects Of Claudin-1 Downregulation On The Physiologicaprocesses Of Gallbladder Cancer Sgc996 Cells","Abstract":"Gallbladder cancer has a high recurrence and mortality rate, with limited treatment options. Therefore, elucidating the underlying molecular mechanisms of this disease would be beneficial to achieve an earlier diagnosis and potentially identify novel treatment targets. Claudin-1 is a tight junction protein associated with the development and prognosis of several types of cancer, and our preliminary studies have demonstrated that claudin-1 expression is elevated in gallbladder cancer tissues. Therefore, the aim of the present study was to investigate the effects of downregulating claudin-1 on the physiological processes of gallbladder cancer cells. The gallbladder cancer SGC996 cell line was transfected with claudin-1-RNA interference lentivirus (LV-CLDN1-RNAi) to downregulate claudin-1 expression, and the downstream effects on cell proliferation, the cell cycle, apoptosis and cell invasion were investigated. Following transfection with LV-CLDN1-RNAi, the results of an MTT assay revealed that downregulating claudin-1 did not affect the proliferation of the SGC996 cells. However, flow cytometry analysis demonstrated that the number of cells arrested in the G1 phase increased significantly, whereas the amount of cells arrested in the S phase was significantly reduced. Annexin V-APC single-color staining demonstrated that downregulating claudin-1 expression increased the ratio of cell apoptosis, which was confirmed by the results of western blot analysis, in which levels of the pro-apoptotic B-cell lymphoma 2 (Bcl-2)-associated X protein and anti-apoptotic Bcl-2 protein were increased and decreased, respectively. Finally, a Transwell assay indicated that claudin-1 downregulation inhibited cell invasion. Overall, the results from the present study indicated that downregulating claudin-1 expression promoted the apoptosis of gallbladder cancer cells and inhibited cell invasion, indicating that claudin-1 may be involved in the recurrence and metastasis of gallbladder cancer. These insights provide theoretical and experimental foundations for considering claudin-1 as a novel target for the treatment of gallbladder cancer.","Source":"STN","category":"ANIMAL","training_data":"Effects Of Claudin-1 Downregulation On The Physiologicaprocesses Of Gallbladder Cancer Sgc996 Cells Gallbladder cancer has a high recurrence and mortality rate, with limited treatment options. Therefore, elucidating the underlying molecular mechanisms of this disease would be beneficial to achieve an earlier diagnosis and potentially identify novel treatment targets. Claudin-1 is a tight junction protein associated with the development and prognosis of several types of cancer, and our preliminary studies have demonstrated that claudin-1 expression is elevated in gallbladder cancer tissues. Therefore, the aim of the present study was to investigate the effects of downregulating claudin-1 on the physiological processes of gallbladder cancer cells. The gallbladder cancer SGC996 cell line was transfected with claudin-1-RNA interference lentivirus (LV-CLDN1-RNAi) to downregulate claudin-1 expression, and the downstream effects on cell proliferation, the cell cycle, apoptosis and cell invasion were investigated. Following transfection with LV-CLDN1-RNAi, the results of an MTT assay revealed that downregulating claudin-1 did not affect the proliferation of the SGC996 cells. However, flow cytometry analysis demonstrated that the number of cells arrested in the G1 phase increased significantly, whereas the amount of cells arrested in the S phase was significantly reduced. Annexin V-APC single-color staining demonstrated that downregulating claudin-1 expression increased the ratio of cell apoptosis, which was confirmed by the results of western blot analysis, in which levels of the pro-apoptotic B-cell lymphoma 2 (Bcl-2)-associated X protein and anti-apoptotic Bcl-2 protein were increased and decreased, respectively. Finally, a Transwell assay indicated that claudin-1 downregulation inhibited cell invasion. Overall, the results from the present study indicated that downregulating claudin-1 expression promoted the apoptosis of gallbladder cancer cells and inhibited cell invasion, indicating that claudin-1 may be involved in the recurrence and metastasis of gallbladder cancer. These insights provide theoretical and experimental foundations for considering claudin-1 as a novel target for the treatment of gallbladder cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"pro apoptotic activity asiatic acid human cholangiocarcinoma cells asiatic acid triterpene found centella asiatica l urban exerts wide variety biological effects including antioxidant anti inflammatory anti cancer activities cholangiocarcinoma cca malignancy bile duct epithelial cells leading cause death thailand current treatments cca sufficiently effective still urgent need find effective strategies prevention treatment cca study sought assess anti cancer effects asiatic acid two human cca cell lines kku 156 kku 213 measurement cell viability using srb assay detection apoptotic cells flow cytometry analysis mrna expression levels apoptosis related genes real time pcr results showed asiatic acid efficiently suppressed cca cellular viability via induction apoptosis evidenced microscopic observation apoptotic vesicles regulation anti apoptotic genes bcl2 survivin birc5 increased early late apoptotic cells findings shed light application plant derived asiatic acid cca prevention treatment google scholar","probabilities":0.9467213,"Title":"Pro-Apoptotic Activity Of Asiatic Acid Against Human Cholangiocarcinoma Cells","Abstract":"Asiatic acid, a triterpene found in Centella asiatica (L.) Urban, exerts a wide variety of biological effects including antioxidant, anti-\ninflammatory and anti-cancer activities. Cholangiocarcinoma (CCA), a malignancy of bile duct epithelial cells, is a leading cause of death in\nThailand. As current treatments for CCA are not sufficiently effective, there is still an urgent need to find effective strategies for prevention\nand treatment of CCA. This study sought to assess the anti-cancer effects of asiatic acid on two human CCA cell lines (KKU-156 and KKU-213)\nthrough measurement of cell viability using SRB assay, detection of apoptotic cells by flow cytometry and analysis of mRNA expression levels\nof apoptosis-related genes by real-time PCR. The results showed that asiatic acid efficiently suppressed CCA cellular viability via induction of\napoptosis as evidenced by microscopic observation of apoptotic vesicles, down-regulation of anti-apoptotic genes (BCL2 and\nSurvivin/BIRC5) and increased early and late apoptotic cells. These findings shed a light on the application of the plant-derived asiatic acid in\nCCA prevention and treatment","Source":"Google Scholar","category":"ANIMAL","training_data":"Pro-Apoptotic Activity Of Asiatic Acid Against Human Cholangiocarcinoma Cells Asiatic acid, a triterpene found in Centella asiatica (L.) Urban, exerts a wide variety of biological effects including antioxidant, anti-\ninflammatory and anti-cancer activities. Cholangiocarcinoma (CCA), a malignancy of bile duct epithelial cells, is a leading cause of death in\nThailand. As current treatments for CCA are not sufficiently effective, there is still an urgent need to find effective strategies for prevention\nand treatment of CCA. This study sought to assess the anti-cancer effects of asiatic acid on two human CCA cell lines (KKU-156 and KKU-213)\nthrough measurement of cell viability using SRB assay, detection of apoptotic cells by flow cytometry and analysis of mRNA expression levels\nof apoptosis-related genes by real-time PCR. The results showed that asiatic acid efficiently suppressed CCA cellular viability via induction of\napoptosis as evidenced by microscopic observation of apoptotic vesicles, down-regulation of anti-apoptotic genes (BCL2 and\nSurvivin/BIRC5) and increased early and late apoptotic cells. These findings shed a light on the application of the plant-derived asiatic acid in\nCCA prevention and treatment Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"alcohol consumption site specific cancer risk comprehensive dose response meta analysis background alcohol risk factor cancer oral cavity pharynx oesophagus colorectum liver larynx female breast whereas impact cancers remains controversial methods investigated effect alcohol 23 cancer types meta analytic approach used dose response meta regression models investigated potential sources heterogeneity results total 572 studies including 486 538 cancer cases identified relative risks rrs heavy drinkers compared nondrinkers occasional drinkers 5 13 oral pharyngeal cancer 4 95 oesophageal squamous cell carcinoma 1 44 colorectal 2 65 laryngeal 1 61 breast cancer neoplasms clear dose risk relationship heavy drinkers also significantly higher risk cancer stomach rr 1 21 liver 2 07 gallbladder 2 64 pancreas 1 19 lung 1 15 indication positive association alcohol consumption risk melanoma prostate cancer alcohol consumption risk hodgkin non hodgkin lymphomas inversely associated conclusions alcohol increases risk cancer oral cavity pharynx oesophagus colorectum liver larynx female breast accumulating evidence alcohol drinking associated cancers pancreas prostate cancer melanoma pubmed","probabilities":0.962963,"Title":"Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis","Abstract":"BACKGROUND: Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial. METHODS: We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose-response meta-regression models and investigated potential sources of heterogeneity. RESULTS: A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose-risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated. CONCLUSIONS: Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma.","Source":"PubMed","category":"HUMAN","training_data":"Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis BACKGROUND: Alcohol is a risk factor for cancer of the oral cavity, pharynx, oesophagus, colorectum, liver, larynx and female breast, whereas its impact on other cancers remains controversial. METHODS: We investigated the effect of alcohol on 23 cancer types through a meta-analytic approach. We used dose-response meta-regression models and investigated potential sources of heterogeneity. RESULTS: A total of 572 studies, including 486 538 cancer cases, were identified. Relative risks (RRs) for heavy drinkers compared with nondrinkers and occasional drinkers were 5.13 for oral and pharyngeal cancer, 4.95 for oesophageal squamous cell carcinoma, 1.44 for colorectal, 2.65 for laryngeal and 1.61 for breast cancer; for those neoplasms there was a clear dose-risk relationship. Heavy drinkers also had a significantly higher risk of cancer of the stomach (RR 1.21), liver (2.07), gallbladder (2.64), pancreas (1.19) and lung (1.15). There was indication of a positive association between alcohol consumption and risk of melanoma and prostate cancer. Alcohol consumption and risk of Hodgkin's and Non-Hodgkin's lymphomas were inversely associated. CONCLUSIONS: Alcohol increases risk of cancer of oral cavity and pharynx, oesophagus, colorectum, liver, larynx and female breast. There is accumulating evidence that alcohol drinking is associated with some other cancers such as pancreas and prostate cancer and melanoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiological aspects biliary tree tumors region northern italy emerging trends sex based differences background cholangiocarcinoma cca gallbladder cancer second cause liver malignancy hepatocellular carcinoma epidemiological data point increase incidence cca western eastern countries however data recent years lacking aims aim study elucidate recent epidemiology cca gallbladder carcinoma north east italy using automatically collected regional data hospital admissions 10 year period materials methods performed retrospective analysis veneto region north east italy database patients hospital discharge records identifying cases following codes intrahepatic cholangiocarcinoma 155 1 primary gallbladder cancer 156 0 primary extrahepatic biliary tract cancer 156 1 hospitalizations recorded according surgical medical procedures involved based international classification diseases 9 procedure codes first hospitalization considered 2005 2009 period results number hospitalizations biliary tumors whole remained stable past 10 years hospitalization rate intrahepatic cca increasing cancer frequent males females hospitalization rate gallbladder cancer increasing age however figures extrahepatic cca remained stable past 10 years duration survival significantly longer patients underwent radical surgery conclusion efforts needed prevent cca bearing mind emerging conditions associated onset secondary prevention tumors substantially improve duration survival pubmed","probabilities":0.9799733,"Title":"Epidemiological aspects of biliary tree tumors in a region of northern Italy: emerging trends and sex-based differences","Abstract":"BACKGROUND: Cholangiocarcinoma (CCA) and gallbladder cancer are the second cause of liver malignancy after hepatocellular carcinoma. Epidemiological data point to an increase in the incidence of CCA in both western and eastern countries; however, data on more recent years are lacking. AIMS: The aim of this study was to elucidate the more recent epidemiology of CCA and gallbladder carcinoma in north-east Italy using automatically collected regional data on hospital admissions over a 10-year period. MATERIALS AND METHODS: We performed a retrospective analysis of the Veneto region (north-east Italy) database of patients' hospital discharge records, identifying cases with the following codes: intrahepatic cholangiocarcinoma (155.1), primary gallbladder cancer (156.0), and primary extrahepatic biliary tract cancer (156.1). Hospitalizations were recorded according to the surgical or medical procedures involved (based on International Classification of Diseases-9 procedure codes), and only the first hospitalization was considered for the 2005-2009 period. RESULTS: The number of hospitalizations for biliary tumors as a whole has remained stable over the past 10 years. The hospitalization rate of intrahepatic CCA is increasing; this cancer is more frequent in males than in females. The hospitalization rate for gallbladder cancer is increasing with age. However, the figures for extrahepatic CCA have remained stable over the past 10 years. The duration of survival was significantly longer for patients who underwent radical surgery than for those who did not. CONCLUSION: Efforts are needed to prevent CCA, bearing in mind the emerging conditions associated with its onset. Secondary prevention of these tumors will substantially improve the duration of survival.","Source":"PubMed","category":"HUMAN","training_data":"Epidemiological aspects of biliary tree tumors in a region of northern Italy: emerging trends and sex-based differences BACKGROUND: Cholangiocarcinoma (CCA) and gallbladder cancer are the second cause of liver malignancy after hepatocellular carcinoma. Epidemiological data point to an increase in the incidence of CCA in both western and eastern countries; however, data on more recent years are lacking. AIMS: The aim of this study was to elucidate the more recent epidemiology of CCA and gallbladder carcinoma in north-east Italy using automatically collected regional data on hospital admissions over a 10-year period. MATERIALS AND METHODS: We performed a retrospective analysis of the Veneto region (north-east Italy) database of patients' hospital discharge records, identifying cases with the following codes: intrahepatic cholangiocarcinoma (155.1), primary gallbladder cancer (156.0), and primary extrahepatic biliary tract cancer (156.1). Hospitalizations were recorded according to the surgical or medical procedures involved (based on International Classification of Diseases-9 procedure codes), and only the first hospitalization was considered for the 2005-2009 period. RESULTS: The number of hospitalizations for biliary tumors as a whole has remained stable over the past 10 years. The hospitalization rate of intrahepatic CCA is increasing; this cancer is more frequent in males than in females. The hospitalization rate for gallbladder cancer is increasing with age. However, the figures for extrahepatic CCA have remained stable over the past 10 years. The duration of survival was significantly longer for patients who underwent radical surgery than for those who did not. CONCLUSION: Efforts are needed to prevent CCA, bearing in mind the emerging conditions associated with its onset. Secondary prevention of these tumors will substantially improve the duration of survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcome patients receiving chemotherapy advanced biliary tract gallbladder carcinoma purpose patients cholangiocarcinoma gallbladder cancer poor overall prognosis management often complex currently standard chemotherapy disease several single agents combinations shown promising activity notably gemcitabine based combinations patients methods conducted retrospective analysis cases biliary tract cancer treated two academic centers lyon france 127 cases identified 67 underwent primary surgery 13 deemed unresectable upon surgery treated medically 60 patients received medical treatment overall 71 patients received chemotherapy locally advanced metastatic disease subject report results median age 60 7 years 47 66 patients male 55 77 patients metastatic disease twenty seven patients 38 required biliary drainage chemotherapy twenty four patients received single agent gemcitabine 37 patients received gemcitabine platinum combination 10 patients received fluorouracil based regimens response rates median progression free survival overall survival times 24 4 1 7 5 months respectively significant increase response rate gemcitabine platinum combinations compared regimens fluororuracil based regimens provided lower response rates shorter median progression free survival overall survival compared gemcitabine based regimens single agents combinations conclusion although retrospective data support use gemcitabine containing regimens patients advanced biliary tract gallbladder cancer benefit adding oxaliplatin setting remains unclear pubmed","probabilities":0.9799733,"Title":"Outcome of patients receiving chemotherapy for advanced biliary tract or gallbladder carcinoma","Abstract":"PURPOSE: Patients with cholangiocarcinoma or gallbladder cancer have poor overall prognosis and their management is often complex. Currently, there is no standard chemotherapy for this disease, but several single agents and combinations have shown promising activity, most notably gemcitabine-based combinations. PATIENTS AND METHODS: We conducted a retrospective analysis of all cases of biliary tract cancer treated at two academic centers in Lyon, France: 127 cases were identified, 67 underwent primary surgery, 13 of which were deemed unresectable upon surgery and were treated medically; 60 patients received medical treatment only. Overall, 71 patients received chemotherapy for locally advanced or metastatic disease and are the subject of this report. RESULTS: The median age was 60.7 years, 47 (66%) patients were male and 55 (77%) patients had metastatic disease. Twenty-seven patients (38%) required biliary drainage before chemotherapy. Twenty-four patients received single-agent gemcitabine, 37 patients received gemcitabine-platinum combination and 10 patients received fluorouracil-based regimens. The response rates, median progression-free survival and overall survival times were 24%, 4.1, 7.5 months, respectively. There was a significant increase in the response rate with gemcitabine-platinum combinations compared with other regimens. Fluororuracil-based regimens provided lower response rates and shorter median progression-free survival and overall survival as compared with gemcitabine-based regimens (both single agents and combinations). CONCLUSION: Although retrospective, these data support the use of gemcitabine-containing regimens in patients with advanced biliary tract or gallbladder cancer. The benefit of adding oxaliplatin in this setting remains unclear.","Source":"PubMed","category":"HUMAN","training_data":"Outcome of patients receiving chemotherapy for advanced biliary tract or gallbladder carcinoma PURPOSE: Patients with cholangiocarcinoma or gallbladder cancer have poor overall prognosis and their management is often complex. Currently, there is no standard chemotherapy for this disease, but several single agents and combinations have shown promising activity, most notably gemcitabine-based combinations. PATIENTS AND METHODS: We conducted a retrospective analysis of all cases of biliary tract cancer treated at two academic centers in Lyon, France: 127 cases were identified, 67 underwent primary surgery, 13 of which were deemed unresectable upon surgery and were treated medically; 60 patients received medical treatment only. Overall, 71 patients received chemotherapy for locally advanced or metastatic disease and are the subject of this report. RESULTS: The median age was 60.7 years, 47 (66%) patients were male and 55 (77%) patients had metastatic disease. Twenty-seven patients (38%) required biliary drainage before chemotherapy. Twenty-four patients received single-agent gemcitabine, 37 patients received gemcitabine-platinum combination and 10 patients received fluorouracil-based regimens. The response rates, median progression-free survival and overall survival times were 24%, 4.1, 7.5 months, respectively. There was a significant increase in the response rate with gemcitabine-platinum combinations compared with other regimens. Fluororuracil-based regimens provided lower response rates and shorter median progression-free survival and overall survival as compared with gemcitabine-based regimens (both single agents and combinations). CONCLUSION: Although retrospective, these data support the use of gemcitabine-containing regimens in patients with advanced biliary tract or gallbladder cancer. The benefit of adding oxaliplatin in this setting remains unclear. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect coffee consumption cholangiocarcinoma risk survival abstract available google scholar","probabilities":0.9799733,"Title":"Effect Of Coffee Consumption On Cholangiocarcinoma Risk And Survival","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Effect Of Coffee Consumption On Cholangiocarcinoma Risk And Survival Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"case series 17 patients cholangiocarcinoma among young adult workers printing company japan background outbreak cholangiocarcinoma occurred among workers offset color proof printing department printing company japan aim study clarify characteristics patients cholangiocarcinoma methods retrospective study conducted 13 japanese hospitals 1996 2013 clinicopathological findings cholangiocarcinoma developed 17 111 former current workers department investigated workers relatively young results cholangiocarcinoma diagnosed 25 45 years old exposed chemicals including dichloromethane 1 2 dichloropropane serum glutamyl transpeptidase activity elevated patients dilated intrahepatic bile ducts without tumor induced obstruction observed five patients cholangiocarcinomas arose large bile ducts precancerous early cancerous lesions biliary intraepithelial neoplasia intraductal papillary neoplasm bile ducts well non specific bile duct injuries fibrosis observed various sites bile ducts eight patients operative specimens available conclusions present results showed cholangiocarcinomas occurred high incidence relatively young workers printing company exposed chemicals including chlorinated organic solvents pubmed","probabilities":0.9799733,"Title":"Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan","Abstract":"BACKGROUND: An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma. METHODS: This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young. RESULTS: The cholangiocarcinoma was diagnosed at 25-45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available. CONCLUSIONS: The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents.","Source":"PubMed","category":"HUMAN","training_data":"Case series of 17 patients with cholangiocarcinoma among young adult workers of a printing company in Japan BACKGROUND: An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma. METHODS: This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young. RESULTS: The cholangiocarcinoma was diagnosed at 25-45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available. CONCLUSIONS: The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents. PubMed","prediction_labels":"HUMAN"},{"cleaned":"diagnosis endoscopic management primary sclerosing cholangitis primary sclerosing cholangitis psc complex chronic progressive fibroinflammatory destructive cholestatic biliary disease exact etiology pathogenesis unknown possibly related enhanced immune mediated response reaction biliary system psc closely associated inflammatory bowel disease specifically ulcerative colitis characterized intrahepatic extrahepatic bile duct stricturing dilation clinical manifestations include abnormal liver tests jaundice pruritus fatigue advanced stages psc progress cirrhosis posttransplant disease recurrence uncommon psc associated increased risk cholangiocarcinoma independent risk factor colorectal cancer patients concomitant inflammatory bowel disease cholangiography mainstay psc diagnosis improved noninvasive biliary imaging shifted role endoscopic retrograde cholangiopancreatography disease diagnosis management complications including dominant biliary strictures bile duct stones assisting differentiation benign vs malignant strictures role additional endoscopic modalities including endoscopic ultrasound direct cholangioscopy probe based confocal laser endomicroscopy evolving present time medical treatment options limited role endoscopy mainly supportive google scholar","probabilities":0.9799733,"Title":"Diagnosis And Endoscopic Management Of Primary Sclerosing Cholangitis","Abstract":"Primary sclerosing cholangitis (PSC) is a complex, chronic, and progressive fibroinflammatory destructive cholestatic biliary disease. The exact etiology and pathogenesis are unknown and possibly related to an enhanced immune-mediated response and reaction in the biliary system. PSC is closely associated with inflammatory bowel disease and specifically, ulcerative colitis. It can be characterized by both intrahepatic and extrahepatic bile duct stricturing and dilation. Clinical manifestations include abnormal liver tests, jaundice, pruritus, and fatigue. At more advanced stages, PSC can progress to cirrhosis and posttransplant disease recurrence is not uncommon. PSC is associated with an increased risk of cholangiocarcinoma and is an independent risk factor for colorectal cancer in patients with concomitant inflammatory bowel disease. Cholangiography is the mainstay of PSC diagnosis. Improved noninvasive biliary imaging has shifted the role of endoscopic retrograde cholangiopancreatography from disease diagnosis to management of complications, including dominant biliary strictures, bile duct stones, and assisting in the differentiation of benign vs malignant strictures. The role of additional endoscopic modalities, including endoscopic ultrasound, direct cholangioscopy, and probe-based confocal laser endomicroscopy is evolving. At the present time, medical treatment options are limited and the role of endoscopy is mainly supportive.","Source":"Google Scholar","category":"HUMAN","training_data":"Diagnosis And Endoscopic Management Of Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is a complex, chronic, and progressive fibroinflammatory destructive cholestatic biliary disease. The exact etiology and pathogenesis are unknown and possibly related to an enhanced immune-mediated response and reaction in the biliary system. PSC is closely associated with inflammatory bowel disease and specifically, ulcerative colitis. It can be characterized by both intrahepatic and extrahepatic bile duct stricturing and dilation. Clinical manifestations include abnormal liver tests, jaundice, pruritus, and fatigue. At more advanced stages, PSC can progress to cirrhosis and posttransplant disease recurrence is not uncommon. PSC is associated with an increased risk of cholangiocarcinoma and is an independent risk factor for colorectal cancer in patients with concomitant inflammatory bowel disease. Cholangiography is the mainstay of PSC diagnosis. Improved noninvasive biliary imaging has shifted the role of endoscopic retrograde cholangiopancreatography from disease diagnosis to management of complications, including dominant biliary strictures, bile duct stones, and assisting in the differentiation of benign vs malignant strictures. The role of additional endoscopic modalities, including endoscopic ultrasound, direct cholangioscopy, and probe-based confocal laser endomicroscopy is evolving. At the present time, medical treatment options are limited and the role of endoscopy is mainly supportive. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"feasibility benefits second line chemotherapy advanced biliary tract cancer large retrospective study introduction first line chemotherapy ct1 effective advanced biliary tract cancer abtc benefits second line chemotherapy ct2 unclear methods retrospectively studied patients starting least one line chemotherapy abtc institution 1991 2011 analysed patient chemotherapy characteristics order 1 characterise patients eligible ct2 2 evaluate efficacy ct2 results three hundred seventy eight received ct1 96 25 patients received ct2 primary tumour location gallbladder 29 intraphepatic 20 perihilar 16 distal common bile duct 19 ampulla vater 14 ninety percent baseline performance status ps 0 1 prior ct1 females p 0 03 ages 60 years p 0 001 patients progression free survival pfs 6 months following ct1 p 0 01 likely offered ct2 objective response rates stable disease ct2 9 34 respectively median pfs median overall survival os beginning ct2 2 8 7 5 months respectively prognostic factors impacting pfs ct2 regimen type doublet versus monotherapy p 0 001 ps 2 p 0 0001 conclusions among patients abtc 25 received ct2 typically younger patients longer pfs following ct1 disease control occurred 43 patients often doublet single agent however clearly effective therapies must found pubmed","probabilities":0.9799733,"Title":"Feasibility and benefits of second-line chemotherapy in advanced biliary tract cancer: a large retrospective study","Abstract":"INTRODUCTION: First-line chemotherapy (CT1) is effective in advanced biliary tract cancer (ABTC). The benefits of second-line chemotherapy (CT2) are unclear. METHODS: We retrospectively studied all patients starting at least one line of chemotherapy for ABTC at our institution between 1991 and 2011. We analysed patient and chemotherapy characteristics in order to: (1) characterise patients eligible for CT2; (2) evaluate the efficacy of CT2. RESULTS: Three hundred and seventy-eight received CT1 and 96 (25%) patients received CT2. Primary tumour location was the gallbladder (29%), intraphepatic (20%), perihilar (16%), distal common bile duct (19%) and ampulla of Vater (14%). Ninety percent had a baseline performance status (PS) of 0-1 prior to CT1. Females (p=0.03), ages ≤ 60 years (p=0.001) and patients with progression free survival (PFS) ≥ 6 months following CT1 (p=0.01) were more likely to be offered CT2. Objective response rates and stable disease with CT2 were 9% and 34%, respectively. Median PFS and median overall survival (OS) from the beginning of CT2 were 2.8 and 7.5 months, respectively. Prognostic factors impacting PFS with CT2 were the regimen type (doublet versus monotherapy, p=0.001) and PS<2 (p<0.0001). CONCLUSIONS: Among patients with ABTC, 25% received CT2, typically younger patients and those with longer PFS following CT1. Disease control occurred in 43% of patients, and more often with a doublet than a single agent. However, clearly more effective therapies must be found.","Source":"PubMed","category":"HUMAN","training_data":"Feasibility and benefits of second-line chemotherapy in advanced biliary tract cancer: a large retrospective study INTRODUCTION: First-line chemotherapy (CT1) is effective in advanced biliary tract cancer (ABTC). The benefits of second-line chemotherapy (CT2) are unclear. METHODS: We retrospectively studied all patients starting at least one line of chemotherapy for ABTC at our institution between 1991 and 2011. We analysed patient and chemotherapy characteristics in order to: (1) characterise patients eligible for CT2; (2) evaluate the efficacy of CT2. RESULTS: Three hundred and seventy-eight received CT1 and 96 (25%) patients received CT2. Primary tumour location was the gallbladder (29%), intraphepatic (20%), perihilar (16%), distal common bile duct (19%) and ampulla of Vater (14%). Ninety percent had a baseline performance status (PS) of 0-1 prior to CT1. Females (p=0.03), ages ≤ 60 years (p=0.001) and patients with progression free survival (PFS) ≥ 6 months following CT1 (p=0.01) were more likely to be offered CT2. Objective response rates and stable disease with CT2 were 9% and 34%, respectively. Median PFS and median overall survival (OS) from the beginning of CT2 were 2.8 and 7.5 months, respectively. Prognostic factors impacting PFS with CT2 were the regimen type (doublet versus monotherapy, p=0.001) and PS<2 (p<0.0001). CONCLUSIONS: Among patients with ABTC, 25% received CT2, typically younger patients and those with longer PFS following CT1. Disease control occurred in 43% of patients, and more often with a doublet than a single agent. However, clearly more effective therapies must be found. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical resection downsizing chemotherapy initially unresectable locally advanced biliary tract cancer retrospective single center study background surgical resection method curative treatment biliary tract cancer btc recently improved efficacy revealed patients initially unresectable locally advanced btc improve prognosis advent useful cancer chemotherapy aim study evaluate effect downsizing chemotherapy patients initially unresectable locally advanced btc methods initially unresectable locally advanced cases defined therapeutic resection achieved even proactive surgical resection gemcitabine administered intravenously week 3 weeks followed 1 week respite patients whose disease responded chemotherapy reevaluated determine whether tumor resectable results chemotherapy gemcitabine provided 22 patients initially unresectable locally advanced btc tumor significantly downsized nine patients surgical resection performed 8 36 4 22 patients surgical resection resulted r0 resection four patients r1 resection four patients patients underwent surgical resection significantly longer survival compared unable undergo surgery conclusions preoperative chemotherapy enables downsizing initially unresectable locally advanced btc radical resection made possible certain proportion patients downsizing chemotherapy proactively carried multidisciplinary treatment strategy patients initially unresectable locally advanced btc aim expanding surgical indication pubmed","probabilities":0.9799733,"Title":"Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study","Abstract":"BACKGROUND: Surgical resection is the only method for curative treatment of biliary tract cancer (BTC). Recently, an improved efficacy has been revealed in patients with initially unresectable locally advanced BTC to improve the prognosis by the advent of useful cancer chemotherapy. The aim of this study was to evaluate the effect of downsizing chemotherapy in patients with initially unresectable locally advanced BTC. METHODS: Initially unresectable locally advanced cases were defined as those in which therapeutic resection could not be achieved even by proactive surgical resection. Gemcitabine was administered intravenously once a week for 3 weeks followed by 1 week's respite. Patients whose disease responded to chemotherapy were reevaluated to determine whether their tumor was resectable. RESULTS: Chemotherapy with gemcitabine was provided to 22 patients with initially unresectable locally advanced BTC. Tumor was significantly downsized in nine patients, and surgical resection was performed in 8 (36.4%) of 22 patients. Surgical resection resulted in R0 resection in four patients and R1 resection in four patients. Patients who underwent surgical resection had a significantly longer survival compared with those unable to undergo surgery. CONCLUSIONS: Preoperative chemotherapy enables the downsizing of initially unresectable locally advanced BTC, with radical resection made possible in a certain proportion of patients. Downsizing chemotherapy should be proactively carried out as a multidisciplinary treatment strategy for patients with initially unresectable locally advanced BTC with the aim of expanding the surgical indication.","Source":"PubMed","category":"HUMAN","training_data":"Surgical resection after downsizing chemotherapy for initially unresectable locally advanced biliary tract cancer: a retrospective single-center study BACKGROUND: Surgical resection is the only method for curative treatment of biliary tract cancer (BTC). Recently, an improved efficacy has been revealed in patients with initially unresectable locally advanced BTC to improve the prognosis by the advent of useful cancer chemotherapy. The aim of this study was to evaluate the effect of downsizing chemotherapy in patients with initially unresectable locally advanced BTC. METHODS: Initially unresectable locally advanced cases were defined as those in which therapeutic resection could not be achieved even by proactive surgical resection. Gemcitabine was administered intravenously once a week for 3 weeks followed by 1 week's respite. Patients whose disease responded to chemotherapy were reevaluated to determine whether their tumor was resectable. RESULTS: Chemotherapy with gemcitabine was provided to 22 patients with initially unresectable locally advanced BTC. Tumor was significantly downsized in nine patients, and surgical resection was performed in 8 (36.4%) of 22 patients. Surgical resection resulted in R0 resection in four patients and R1 resection in four patients. Patients who underwent surgical resection had a significantly longer survival compared with those unable to undergo surgery. CONCLUSIONS: Preoperative chemotherapy enables the downsizing of initially unresectable locally advanced BTC, with radical resection made possible in a certain proportion of patients. Downsizing chemotherapy should be proactively carried out as a multidisciplinary treatment strategy for patients with initially unresectable locally advanced BTC with the aim of expanding the surgical indication. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment outcomes prognostic factors intrahepatic cholangiocarcinoma aim present study determine treatment outcome prognostic factors survival patients peripheral intrahepatic cholangiocarcinoma icc retrospective chart review performed patients diagnosed icc 2000 2009 single institution identified total 105 patients icc among 63 8 older 60 years age 50 5 male 88 6 caucasian preoperative imaging approximately half patients 50 5 surgical candidates underwent resection half patients 49 5 unresectable unresectable group received chemoradiotherapy 53 transarterial chemoembolization 7 7 palliative treatments 23 0 patients 12 52 received best supportive care alone median survival rates 16 1 months 13 1 19 2 entire cohort 27 6 months 17 7 37 6 curative resection 12 9 months 6 5 19 2 palliative chemoradiotherapy 4 9 months 0 4 9 6 best supportive care p 0 001 independent predictors multivariate analysis advanced stage diagnosis treatment received patients underwent resection advanced ajcc stage presence microvascular invasion also independent predictors poor survival concluded surgery offers beneficial curative option outcome emphasizing importance resectability major prognostic factor present study also revealed use chemoradiotherapy adjuvant setting failed improve survival palliative use patients unresectable icc offered modest survival advantage best supportive care overriding factors influencing outcome stage presence microvascular invasion pathology pubmed","probabilities":0.9799733,"Title":"Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma","Abstract":"The aim of the present study was to determine the treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC). A retrospective chart review was performed for patients diagnosed with ICC between 2000 and 2009 at a single institution. We identified a total of 105 patients with ICC. Among them, 63.8% were older than 60 years of age, 50.5% were male and 88.6% were Caucasian. By preoperative imaging approximately half of the patients (50.5%) were surgical candidates and underwent resection. The other half of the patients (49.5%) were unresectable. The unresectable group received chemoradiotherapy (53%) and transarterial chemoembolization (7.7%) as palliative treatments while 23.0% of the patients (12/52) received best supportive care alone. The median survival rates were 16.1 months (13.1‑19.2) for the entire cohort, 27.6 months (17.7-37.6) for curative resection, 12.9 months (6.5-19.2) for palliative chemoradiotherapy and 4.9 months (0.4-9.6) for best supportive care (p<0.001). Independent predictors on multivariate analysis were advanced stage at diagnosis and treatment received. In those patients who underwent resection, advanced AJCC stage and presence of microvascular invasion were also independent predictors of poor survival. We concluded that surgery offers the most beneficial curative option and outcome, emphasizing the importance of resectability as a major prognostic factor. The present study also revealed that use of chemoradiotherapy in the adjuvant setting failed to improve survival but its palliative use in those patients with unresectable ICC offered a modest survival advantage over best supportive care. The overriding factors influencing outcome were stage and the presence of microvascular invasion on pathology.","Source":"PubMed","category":"HUMAN","training_data":"Treatment outcomes and prognostic factors of intrahepatic cholangiocarcinoma The aim of the present study was to determine the treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC). A retrospective chart review was performed for patients diagnosed with ICC between 2000 and 2009 at a single institution. We identified a total of 105 patients with ICC. Among them, 63.8% were older than 60 years of age, 50.5% were male and 88.6% were Caucasian. By preoperative imaging approximately half of the patients (50.5%) were surgical candidates and underwent resection. The other half of the patients (49.5%) were unresectable. The unresectable group received chemoradiotherapy (53%) and transarterial chemoembolization (7.7%) as palliative treatments while 23.0% of the patients (12/52) received best supportive care alone. The median survival rates were 16.1 months (13.1‑19.2) for the entire cohort, 27.6 months (17.7-37.6) for curative resection, 12.9 months (6.5-19.2) for palliative chemoradiotherapy and 4.9 months (0.4-9.6) for best supportive care (p<0.001). Independent predictors on multivariate analysis were advanced stage at diagnosis and treatment received. In those patients who underwent resection, advanced AJCC stage and presence of microvascular invasion were also independent predictors of poor survival. We concluded that surgery offers the most beneficial curative option and outcome, emphasizing the importance of resectability as a major prognostic factor. The present study also revealed that use of chemoradiotherapy in the adjuvant setting failed to improve survival but its palliative use in those patients with unresectable ICC offered a modest survival advantage over best supportive care. The overriding factors influencing outcome were stage and the presence of microvascular invasion on pathology. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ribonucleotide reductase large subunit rrm1 predictive factor patients cancer large subunit human ribonucleotide reductase rrm1 involved regulation cell proliferation cell migration tumour metastasis development synthesis deoxyribonucleotides dna synthesis also cellular target chemotherapeutic agent gemcitabine rrm1 studied large number patients different types cancer non small cell lung cancer pancreatic cancer breast cancer biliary tract cancer establish prognostic predictive value patients treated gemcitabine mrna expression genetic variants determined genotyping cases associated clinical outcome patients cancer review preclinical clinical studies rrm1 assessment discuss steps development clinically pertinent biomarker pubmed","probabilities":0.962963,"Title":"The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer","Abstract":"The large subunit of human ribonucleotide reductase, RRM1, is involved in the regulation of cell proliferation, cell migration, tumour and metastasis development, and the synthesis of deoxyribonucleotides for DNA synthesis. It is also a cellular target for the chemotherapeutic agent, gemcitabine. RRM1 has been studied in a large number of patients with different types of cancer, such as non-small-cell lung cancer, pancreatic cancer, breast cancer, and biliary tract cancer, to establish its prognostic or predictive value when patients were treated with gemcitabine, and mRNA expression and genetic variants as determined by genotyping have in some cases been associated with clinical outcome of patients with cancer. Here, we review preclinical and clinical studies of RRM1 assessment and discuss the further steps in the development of this clinically pertinent biomarker.","Source":"PubMed","category":"HUMAN","training_data":"The ribonucleotide reductase large subunit (RRM1) as a predictive factor in patients with cancer The large subunit of human ribonucleotide reductase, RRM1, is involved in the regulation of cell proliferation, cell migration, tumour and metastasis development, and the synthesis of deoxyribonucleotides for DNA synthesis. It is also a cellular target for the chemotherapeutic agent, gemcitabine. RRM1 has been studied in a large number of patients with different types of cancer, such as non-small-cell lung cancer, pancreatic cancer, breast cancer, and biliary tract cancer, to establish its prognostic or predictive value when patients were treated with gemcitabine, and mRNA expression and genetic variants as determined by genotyping have in some cases been associated with clinical outcome of patients with cancer. Here, we review preclinical and clinical studies of RRM1 assessment and discuss the further steps in the development of this clinically pertinent biomarker. PubMed","prediction_labels":"HUMAN"},{"cleaned":"inflammatory bowel disease risk cholangiocarcinoma evidence meta analysis population based studies objective patients inflammatory bowel disease ibd increased risk extra intestinal cancer whereas impact cholangiocarcinoma cc remains unknown aim study obtain reliable estimate risk cc ibd patients meta analysis clinical observational studies methods relevant studies retrieved searching pubmed embase web science databases dec 2013 four population based case control two cohort studies ibd identified summary relative risk rr corresponding 95 confidence interval ci calculated using random effects model potential sources heterogeneity detected using subgroup analyses results pooled risk estimate indicated ibd patients increased risk cc rr 2 63 95 ci 1 47 4 72 moreover increased risk cc also associated crohn disease rr 2 69 95 ci 1 59 4 55 ulcerative colitis rr 3 40 95 ci 2 50 4 62 addition site specific analyses revealed ibd patients increased risk intrahepatic cc icc rr 2 61 95 ci 1 72 3 95 extrahepatic cc ecc rr 1 47 95 ci 1 10 1 97 conclusions study suggests risk cc significantly increased among ibd patients especially icc cases studies warranted enable definite conclusions drawn pubmed","probabilities":0.9799733,"Title":"Inflammatory bowel disease and risk of cholangiocarcinoma: evidence from a meta-analysis of population-based studies","Abstract":"OBJECTIVE: Patients with inflammatory bowel disease (IBD) have an increased risk of extra-intestinal cancer, whereas its impact on cholangiocarcinoma (CC) remains unknown. The aim of this study was to obtain a reliable estimate of the risk of CC in IBD patients through a meta-analysis of clinical observational studies. METHODS: Relevant studies were retrieved by searching PUBMED, EMBASE and Web of Science Databases up to Dec 2013. Four population-based case-control and two cohort studies with IBD were identified. Summary relative risk (RR) and its corresponding 95% confidence interval (CI) were calculated using a random-effects model. Potential sources of heterogeneity were detected using subgroup analyses. RESULTS: The pooled risk estimate indicated IBD patients were at increased risk of CC (RR = 2.63, 95%CI = 1.47-4.72). Moreover, the increased risk of CC was also associated with Crohn's disease (RR = 2.69, 95%CI = 1.59-4.55) and ulcerative colitis (RR = 3.40, 95%CI = 2.50-4.62). In addition, site-specific analyses revealed that IBD patients had an increased risk of intrahepatic CC (ICC) (RR = 2.61, 95%CI = 1.72-3.95) and extrahepatic CC (ECC) (RR = 1.47, 95%CI = 1.10- 1.97). CONCLUSIONS: This study suggests the risk of CC is significantly increased among IBD patients, especially in ICC cases. Further studies are warranted to enable definite conclusions to be drawn.","Source":"PubMed","category":"HUMAN","training_data":"Inflammatory bowel disease and risk of cholangiocarcinoma: evidence from a meta-analysis of population-based studies OBJECTIVE: Patients with inflammatory bowel disease (IBD) have an increased risk of extra-intestinal cancer, whereas its impact on cholangiocarcinoma (CC) remains unknown. The aim of this study was to obtain a reliable estimate of the risk of CC in IBD patients through a meta-analysis of clinical observational studies. METHODS: Relevant studies were retrieved by searching PUBMED, EMBASE and Web of Science Databases up to Dec 2013. Four population-based case-control and two cohort studies with IBD were identified. Summary relative risk (RR) and its corresponding 95% confidence interval (CI) were calculated using a random-effects model. Potential sources of heterogeneity were detected using subgroup analyses. RESULTS: The pooled risk estimate indicated IBD patients were at increased risk of CC (RR = 2.63, 95%CI = 1.47-4.72). Moreover, the increased risk of CC was also associated with Crohn's disease (RR = 2.69, 95%CI = 1.59-4.55) and ulcerative colitis (RR = 3.40, 95%CI = 2.50-4.62). In addition, site-specific analyses revealed that IBD patients had an increased risk of intrahepatic CC (ICC) (RR = 2.61, 95%CI = 1.72-3.95) and extrahepatic CC (ECC) (RR = 1.47, 95%CI = 1.10- 1.97). CONCLUSIONS: This study suggests the risk of CC is significantly increased among IBD patients, especially in ICC cases. Further studies are warranted to enable definite conclusions to be drawn. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidermal growth factor upregulates mrna protein levels skp2 cks1 p27kip1 via pi3k akt pathway human extrahepatic cholangiocarcinoma cells aim evaluate expression status phase kinase associated protein 2 skp2 cyclin dependent kinases regulatory subunit 1 cks1 p27 kip1 assess prognostic significance skp2 cks1 expression p27 kip1 patients extrahepatic cholangiocarcinoma methods seventy six patients underwent curative resection histologically confirmed extrahepatic cholangiocarcinoma institution december 1994 march 2008 enrolled immunohistochemical staining skp2 cks1 p27 kip1 ki67 along relevant molecular biologic experiments performed results cox regression analyses advanced age 65 years advanced ajcc tumor stage poorly differentiated histology higher immunostaining intensity skp2 identified independent prognostic factors patients extrahepatic cholangiocarcinoma exogenous epidermal growth factor egf especially 0 1 10 ng ml significantly increased proliferation indices mtt assay mrna levels skp2 cks1 p27 kip1 snu 1196 snu 1079 snu 245 cells protein levels skp2 cks1 nuclear lysates p27 kip1 cytosolic lysate also significantly increased cells significant reductions protein levels skp2 cks1 p27 kip1 nuclear lysate treatment ly294002 chromatin immunoprecipitation assay found e2f1 transcription factor directly binds promoter site skp2 conclusion higher immunostaining intensity skp2 cks1 independent prognostic factor patients extrahepatic cholangiocarcinoma egf upregulates mrna protein levels skp2 cks1 p27 kip1 via pi3k akt pathway direct binding e2f1 transcription factor skp2 promoter stn","probabilities":1.0,"Title":"Epidermal Growth Factor Upregulates The Mrna And Protein Levels Of Skp2/Cks1 And P27Kip1 Via The Pi3K/Akt Pathway In Human Extrahepatic Cholangiocarcinoma Cells","Abstract":"Aim: To evaluate the expression status of S-phase kinase-associated protein 2 (Skp2)/cyclin-dependent kinases regulatory subunit 1 (Cks1) and p27(kip1), and assess the prognostic significance of Skp2/Cks1 expression with p27(kip1) in patients with extrahepatic cholangiocarcinoma. \r\n\r\n Methods: Seventy-six patients who underwent curative resection for histologically confirmed extrahepatic cholangiocarcinoma at our institution from December 1994 to March 2008 were enrolled. Immunohistochemical staining for Skp2, Cks1, p27(kip1), and Ki67, along with other relevant molecular biologic experiments, were performed. \r\n\r\n Results: By Cox regression analyses, advanced age (> 65 years), advanced AJCC tumor stage, poorly differentiated histology, and higher immunostaining intensity of Skp2 were identified as independent prognostic factors in patients with extrahepatic cholangiocarcinoma. Exogenous epidermal growth factor (EGF, especially 0.1-10 ng/mL) significantly increased the proliferation indices by MTT assay and the mRNA levels of Skp2/Cks1 and p27(kip1) in SNU-1196, SNU-1079, and SNU-245 cells. The protein levels of Skp2/Cks1 (from nuclear lysates) and p27(kip1) (from cytosolic lysate) were also significantly increased in these cells. There were significant reductions in the protein levels of Skp2/Cks1 and p27(kip1) (from nuclear lysate) after the treatment of LY294002. By chromatin immunoprecipitation assay, we found that E2F1 transcription factor directly binds to the promoter site of Skp2. \r\n\r\n Conclusion: Higher immunostaining intensity of Skp2/Cks1 was an independent prognostic factor for patients with extrahepatic cholangiocarcinoma. EGF upregulates the mRNA and protein levels of Skp2/Cks1 and p27(kip1) via the PI3K/Akt pathway and direct binding of E2F1 transcription factor with the Skp2 promoter.","Source":"STN","category":"HUMAN","training_data":"Epidermal Growth Factor Upregulates The Mrna And Protein Levels Of Skp2/Cks1 And P27Kip1 Via The Pi3K/Akt Pathway In Human Extrahepatic Cholangiocarcinoma Cells Aim: To evaluate the expression status of S-phase kinase-associated protein 2 (Skp2)/cyclin-dependent kinases regulatory subunit 1 (Cks1) and p27(kip1), and assess the prognostic significance of Skp2/Cks1 expression with p27(kip1) in patients with extrahepatic cholangiocarcinoma. \r\n\r\n Methods: Seventy-six patients who underwent curative resection for histologically confirmed extrahepatic cholangiocarcinoma at our institution from December 1994 to March 2008 were enrolled. Immunohistochemical staining for Skp2, Cks1, p27(kip1), and Ki67, along with other relevant molecular biologic experiments, were performed. \r\n\r\n Results: By Cox regression analyses, advanced age (> 65 years), advanced AJCC tumor stage, poorly differentiated histology, and higher immunostaining intensity of Skp2 were identified as independent prognostic factors in patients with extrahepatic cholangiocarcinoma. Exogenous epidermal growth factor (EGF, especially 0.1-10 ng/mL) significantly increased the proliferation indices by MTT assay and the mRNA levels of Skp2/Cks1 and p27(kip1) in SNU-1196, SNU-1079, and SNU-245 cells. The protein levels of Skp2/Cks1 (from nuclear lysates) and p27(kip1) (from cytosolic lysate) were also significantly increased in these cells. There were significant reductions in the protein levels of Skp2/Cks1 and p27(kip1) (from nuclear lysate) after the treatment of LY294002. By chromatin immunoprecipitation assay, we found that E2F1 transcription factor directly binds to the promoter site of Skp2. \r\n\r\n Conclusion: Higher immunostaining intensity of Skp2/Cks1 was an independent prognostic factor for patients with extrahepatic cholangiocarcinoma. EGF upregulates the mRNA and protein levels of Skp2/Cks1 and p27(kip1) via the PI3K/Akt pathway and direct binding of E2F1 transcription factor with the Skp2 promoter. STN","prediction_labels":"HUMAN"},{"cleaned":"association body mass index prognosis advanced biliary tract cancer patients underwent palliative chemotherapy background aims intrahepatic cholangiocarcinoma icc second common primary liver malignancy arising peripheral intrahepatic bile duct epithelium hepatitis b virus hbv hepatitis c virus hcv may involved development icc aim study identify prognostic value hepatitis virus infections prognostic factors affecting survival patients icc methods retrospective chart review performed patients diagnosed icc august 2005 april 2016 google scholar","probabilities":0.9799733,"Title":"Association Between Body Mass Index And Prognosis In Advanced Biliary Tract Cancer Patients Who Underwent Palliative Chemotherapy","Abstract":"Background/Aims: Intrahepatic cholangiocarcinoma (ICC) is the second most common \nprimary liver malignancy arising from the peripheral intrahepatic bile duct epithelium. \nHepatitis B virus (HBV) and hepatitis C virus (HCV) may be involved in the development of \nICC. The aim of this study is to identify the prognostic value of hepatitis virus infections and \nthe prognostic factors affecting survival in patients with ICC. Methods: A retrospective chart \nreview was performed for patients diagnosed with ICC between August 2005 and April 2016 …","Source":"Google Scholar","category":"HUMAN","training_data":"Association Between Body Mass Index And Prognosis In Advanced Biliary Tract Cancer Patients Who Underwent Palliative Chemotherapy Background/Aims: Intrahepatic cholangiocarcinoma (ICC) is the second most common \nprimary liver malignancy arising from the peripheral intrahepatic bile duct epithelium. \nHepatitis B virus (HBV) and hepatitis C virus (HCV) may be involved in the development of \nICC. The aim of this study is to identify the prognostic value of hepatitis virus infections and \nthe prognostic factors affecting survival in patients with ICC. Methods: A retrospective chart \nreview was performed for patients diagnosed with ICC between August 2005 and April 2016 … Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"gemcitabine cisplatin versus gemcitabine oxaliplatin doublet chemotherapy advanced gallbladder cancers match pair analysis background gemcitabine cisplatin gc gemcitabine oxaliplatin go commonly used regimens advanced gallbladder cancer gbc methods data patients advanced gbc treated january 2013 june 2015 retrieved 1 1 matching without replacement performed using nearest neighbor matching method results total 326 patients 163 gc 163 go matched 1 1 age gender response rates gc go 31 2 36 3 p 0 350 overall median event free survival efs 4 34 months 95 ci 4 030 4 644 months median efs 4 67 months 95 ci 4 060 5 271 months gc cohort 3 88 months 95 ci 3 369 4 385 months go cohort p 0 023 overall median os 8 016 months 95 ci 7 361 8 672 months median os 8 02 months 95 ci 7 257 8 776 months gc cohort 7 79 months 95 ci 6 690 8 88 months go cohort p 0 455 incidence grade 2 3 peripheral neuropathy 9 2 vs 3 1 p 0 445 grade 3 4 transamintis 14 7 vs 6 1 higher go incidence anemia 22 1 vs 6 7 p 0 001 neutropenia 7 3 vs 2 4 p 0 49 thrombocytopenia 9 8 vs 3 7 p 0 033 higher gc conclusion gemcitabine cisplatin gemcitabine oxaliplatin used initial regimen advanced gbc higher efs potentially lower costs lower incidence peripheral neuropathy hepatotoxicity favor use gc whereas lower incidence hematological toxicities potential ease administration patients borderline renal cardiac functions favor go pubmed","probabilities":0.9799733,"Title":"Gemcitabine-cisplatin versus gemcitabine-oxaliplatin doublet chemotherapy in advanced gallbladder cancers: a match pair analysis","Abstract":"BACKGROUND: Gemcitabine-cisplatin (GC) and gemcitabine-oxaliplatin (GO) are the most commonly used regimens in advanced gallbladder cancer (GBC). METHODS: The data of patients with advanced GBC, treated between January 2013 and June 2015 were retrieved. A 1:1 matching without replacement was performed by using nearest neighbor matching method. RESULTS: A total of 326 patients (163 GC and 163 GO), were matched 1:1 by age and gender. The response rates for GC and GO were 31.2% and 36.3% (P = 0.350). The overall median event free survival (EFS) was 4.34 months (95% CI 4.030-4.644 months). The median EFS was 4.67 months (95% CI 4.060-5.271 months) in GC cohort and 3.88 months (95% CI 3.369-4.385 months) in GO cohort (P = 0.023). The overall median OS was 8.016 months (95% CI 7.361-8.672 months). The median OS was 8.02 months (95% CI 7.257-8.776 months) in GC cohort and 7.79 months (95% CI 6.690-8.88 months) in GO cohort (P = 0.455). The incidence of Grade 2/3 peripheral neuropathy (9.2% vs. 3.1%; P = 0.445) and Grade 3/4 transamintis (14.7% vs. 6.1%) was higher with GO while the incidence of anemia (22.1% vs. 6.7%; P < 0.001), neutropenia (7.3% vs. 2.4%; P = 0.49) and thrombocytopenia (9.8% vs. 3.7%; P = 0.033) was higher with GC. CONCLUSION: Gemcitabine-cisplatin or gemcitabine-oxaliplatin can be used as an initial regimen in advanced GBC. Higher EFS, potentially lower costs, lower incidence of peripheral neuropathy and hepatotoxicity favor the use of GC, whereas a lower incidence of hematological toxicities, and potential ease of administration in patients with borderline renal and cardiac functions favor GO.","Source":"PubMed","category":"HUMAN","training_data":"Gemcitabine-cisplatin versus gemcitabine-oxaliplatin doublet chemotherapy in advanced gallbladder cancers: a match pair analysis BACKGROUND: Gemcitabine-cisplatin (GC) and gemcitabine-oxaliplatin (GO) are the most commonly used regimens in advanced gallbladder cancer (GBC). METHODS: The data of patients with advanced GBC, treated between January 2013 and June 2015 were retrieved. A 1:1 matching without replacement was performed by using nearest neighbor matching method. RESULTS: A total of 326 patients (163 GC and 163 GO), were matched 1:1 by age and gender. The response rates for GC and GO were 31.2% and 36.3% (P = 0.350). The overall median event free survival (EFS) was 4.34 months (95% CI 4.030-4.644 months). The median EFS was 4.67 months (95% CI 4.060-5.271 months) in GC cohort and 3.88 months (95% CI 3.369-4.385 months) in GO cohort (P = 0.023). The overall median OS was 8.016 months (95% CI 7.361-8.672 months). The median OS was 8.02 months (95% CI 7.257-8.776 months) in GC cohort and 7.79 months (95% CI 6.690-8.88 months) in GO cohort (P = 0.455). The incidence of Grade 2/3 peripheral neuropathy (9.2% vs. 3.1%; P = 0.445) and Grade 3/4 transamintis (14.7% vs. 6.1%) was higher with GO while the incidence of anemia (22.1% vs. 6.7%; P < 0.001), neutropenia (7.3% vs. 2.4%; P = 0.49) and thrombocytopenia (9.8% vs. 3.7%; P = 0.033) was higher with GC. CONCLUSION: Gemcitabine-cisplatin or gemcitabine-oxaliplatin can be used as an initial regimen in advanced GBC. Higher EFS, potentially lower costs, lower incidence of peripheral neuropathy and hepatotoxicity favor the use of GC, whereas a lower incidence of hematological toxicities, and potential ease of administration in patients with borderline renal and cardiac functions favor GO. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors patients gallbladder cancer surgical resection analysis 279 operated patients background identification prognostic factors help predict life expectancy decide treatment plan evaluated prognostic factors patients gallbladder cancer gbc surgical resection study data 279 patients gbc underwent surgery january 1999 february 2009 reviewed retrospectively results 279 patients 127 45 5 male median age 63 years r0 resection achieved 164 58 8 patients 35 cholecystectomy 129 extended resection chemotherapy radiotherapy performed 72 25 8 55 19 7 patients median follow 17 0 months median overall survival os 26 0 months five year survival rates stages ii iiia iiib iva ivb gbc 94 7 75 7 44 5 21 7 4 7 2 6 respectively compared cholecystectomy extended resection showed improved os stages statistical significance observed t3 p 0 001 t4 p 0 007 although os similar patients received chemotherapy radiotherapy radiotherapy significantly improved os patients positive resection margin p 0 023 low grade histologic type p 0 047 clear resection margin p 0 002 significant predictors increased os epidemiological factors gallstones anomalous pancreaticobiliary ductal union conclusions patients gbc surgical resection tnm stage important prognostic factor prognosis also associated extent resection histologic differentiation involvement resection margin patients positive resection margin radiotherapy seems prolong os pubmed","probabilities":0.9799733,"Title":"Prognostic factors in patients with gallbladder cancer after surgical resection: analysis of 279 operated patients","Abstract":"BACKGROUND: Identification of prognostic factors can help predict life expectancy and decide treatment plan. We evaluated prognostic factors in patients with gallbladder cancer (GBC) after surgical resection. STUDY: Data from 279 patients with GBC who underwent surgery between January 1999 and February 2009 were reviewed retrospectively. RESULTS: Of the 279 patients, 127 (45.5%) were male; median age was 63 years. R0 resection was achieved in 164 (58.8%) patients, 35 by cholecystectomy and 129 by extended resection. Chemotherapy and radiotherapy were performed in 72 (25.8%) and 55 (19.7%) patients. At a median follow-up of 17.0 months, median overall survival (OS) was 26.0 months. Five-year survival rates for stages I, II, IIIA, IIIB, IVA, and IVB GBC were 94.7%, 75.7%, 44.5%, 21.7%, 4.7%, and 2.6%, respectively. Compared with cholecystectomy, extended resection showed improved OS in all T stages, but statistical significance was observed only in T3 (P<0.001) and T4 (P=0.007). Although OS was similar in patients who received chemotherapy or radiotherapy, radiotherapy significantly improved OS in patients with positive resection margin (P=0.023). Low-grade histologic type (P=0.047) and clear resection margin (P=0.002) were significant predictors of increased OS, but epidemiological factors such as gallstones and anomalous pancreaticobiliary ductal union were not. CONCLUSIONS: In patients with GBC after surgical resection, TNM stage was the most important prognostic factor. Prognosis was also associated with extent of resection, histologic differentiation, and involvement of resection margin. In patients with positive resection margin, radiotherapy seems to prolong OS.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors in patients with gallbladder cancer after surgical resection: analysis of 279 operated patients BACKGROUND: Identification of prognostic factors can help predict life expectancy and decide treatment plan. We evaluated prognostic factors in patients with gallbladder cancer (GBC) after surgical resection. STUDY: Data from 279 patients with GBC who underwent surgery between January 1999 and February 2009 were reviewed retrospectively. RESULTS: Of the 279 patients, 127 (45.5%) were male; median age was 63 years. R0 resection was achieved in 164 (58.8%) patients, 35 by cholecystectomy and 129 by extended resection. Chemotherapy and radiotherapy were performed in 72 (25.8%) and 55 (19.7%) patients. At a median follow-up of 17.0 months, median overall survival (OS) was 26.0 months. Five-year survival rates for stages I, II, IIIA, IIIB, IVA, and IVB GBC were 94.7%, 75.7%, 44.5%, 21.7%, 4.7%, and 2.6%, respectively. Compared with cholecystectomy, extended resection showed improved OS in all T stages, but statistical significance was observed only in T3 (P<0.001) and T4 (P=0.007). Although OS was similar in patients who received chemotherapy or radiotherapy, radiotherapy significantly improved OS in patients with positive resection margin (P=0.023). Low-grade histologic type (P=0.047) and clear resection margin (P=0.002) were significant predictors of increased OS, but epidemiological factors such as gallstones and anomalous pancreaticobiliary ductal union were not. CONCLUSIONS: In patients with GBC after surgical resection, TNM stage was the most important prognostic factor. Prognosis was also associated with extent of resection, histologic differentiation, and involvement of resection margin. In patients with positive resection margin, radiotherapy seems to prolong OS. PubMed","prediction_labels":"HUMAN"},{"cleaned":"astrocyte elevated gene 1 novel clinicopathological prognostic biomarker gastrointestinal cancers meta analysis 2999 patients background numerous articles whether staining index si astrocyte elevated gene 1 aeg 1 adversely affects clinical progression prognosis gastrointestinal cancers nevertheless controversy still exists terms correlations aeg 1 si clinicopathological parameters including survival data consequently conducted comprehensive meta analysis confirm role aeg 1 clinical outcomes gastrointestinal carcinoma patients methods performed comprehensive search pubmed isi web science cochrane central register controlled trials embase science direct wiley online library china national knowledge infrastructure cnki wanfang chinese vip databases stata 12 0 stata corp college tx used analyze data extracted suitable studies newcastle ottawa scale applied assess quality included articles results current meta analysis included 2999 patients results suggested strong associations emerged aeg 1 si histological differentiation 2 129 95 ci 1 377 3 290 p 0 001 tumor classification 2 272 95 ci 1 147 4 502 p 0 019 lymph node n classification 2 696 95 ci 2 178 3 337 p 0 001 metastasis m classification 3 731 95 ci 2 167 6 426 p 0 001 furthermore high aeg 1 si significantly associated poor overall survival os hr 2 369 95 ci 2 005 2 800 p 0 001 deteriorated disease free survival dfs hr 1 538 95 ci 1 171 2 020 p 0 002 disease specific survival dss relapse free survival rfs statistically significant results observed hr 1 573 95 ci 0 761 3 250 p 0 222 hr 1 432 95 ci 0 108 19 085 p 0 786 subgroup analysis demonstrated high aeg 1 si significantly related poor prognosis esophageal squamous cell carcinoma escc hr 1 715 95 ci 1 211 2 410 p 0 002 gastric carcinoma gc hr 2 255 95 ci 1 547 3 288 p 0 001 colorectal carcinoma crc hr 2 922 95 ci 1 921 4 444 p 0 001 gallbladder carcinoma gbc hr 3 047 95 ci 1 685 5 509 p 0 001 hepatocellular carcinoma hcc hr 2 245 95 ci 1 620 3 113 p 0 001 pancreatic adenocarcinoma pac hr 2 408 95 ci 1 625 3 568 p 0 001 conclusions current meta analysis indicated high aeg 1 si might associated tumor progression poor survival status patients gastrointestinal cancer aeg 1 might play vital role promoting tumor aggression serve potential target molecular treatments clinical trials needed validate whether aeg 1 si provides valuable insights improving treatment decisions pubmed","probabilities":0.962963,"Title":"Astrocyte Elevated Gene-1 as a Novel Clinicopathological and Prognostic Biomarker for Gastrointestinal Cancers: A Meta-Analysis with 2999 Patients","Abstract":"BACKGROUND: There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients. METHODS: We performed a comprehensive search in PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct, Wiley Online Library, China National Knowledge Infrastructure (CNKI), WanFang and Chinese VIP databases. STATA 12.0 (STATA Corp., College, TX) was used to analyze the data extracted from suitable studies and Newcastle-Ottawa Scale was applied to assess the quality of included articles. RESULTS: The current meta-analysis included 2999 patients and our results suggested that strong associations emerged between AEG-1 SI and histological differentiation (OR = 2.129, 95%CI: 1.377-3.290, P = 0.001), tumor (T) classification (OR = 2.272, 95%CI: 1.147-4.502, P = 0.019), lymph node (N) classification (OR = 2.696, 95%CI: 2.178-3.337, P<0.001) and metastasis (M) classification (OR = 3.731, 95%CI: 2.167-6.426, P<0.001). Furthermore, high AEG-1 SI was significantly associated with poor overall survival (OS) (HR = 2.369, 95%CI: 2.005-2.800, P<0.001) and deteriorated disease-free survival (DFS) (HR = 1.538, 95%CI: 1.171-2.020, P = 0.002). For disease-specific survival (DSS) and relapse-free survival (RFS), no statistically significant results were observed (HR = 1.573, 95%CI: 0.761-3.250, P = 0.222; HR = 1.432, 95%CI: 0.108-19.085, P = 0.786). Subgroup analysis demonstrated that high AEG-1 SI was significantly related to poor prognosis in esophageal squamous cell carcinoma (ESCC) (HR = 1.715, 95%CI: 1.211-2.410, P = 0.002), gastric carcinoma (GC) (HR = 2.255, 95%CI: 1.547-3.288, P<0.001), colorectal carcinoma (CRC) (HR = 2.922, 95%CI: 1.921-4.444, P<0.001), gallbladder carcinoma (GBC) (HR = 3.047, 95%CI: 1.685-5.509, P<0.001), hepatocellular carcinoma (HCC) (HR = 2.245, 95%CI: 1.620-3.113, P<0.001), pancreatic adenocarcinoma (PAC) (HR = 2.408, 95%CI: 1.625-3.568, P<0.001). CONCLUSIONS: The current meta-analysis indicated that high AEG-1 SI might be associated with tumor progression and poor survival status in patients with gastrointestinal cancer. AEG-1 might play a vital role in promoting tumor aggression and could serve as a potential target for molecular treatments. Further clinical trials are needed to validate whether AEG-1 SI provides valuable insights into improving treatment decisions.","Source":"PubMed","category":"HUMAN","training_data":"Astrocyte Elevated Gene-1 as a Novel Clinicopathological and Prognostic Biomarker for Gastrointestinal Cancers: A Meta-Analysis with 2999 Patients BACKGROUND: There have been numerous articles as to whether the staining index (SI) of astrocyte elevated gene-1 (AEG-1) adversely affects clinical progression and prognosis of gastrointestinal cancers. Nevertheless, controversy still exists in terms of correlations between AEG-1 SI and clinicopathological parameters including survival data. Consequently, we conducted a comprehensive meta-analysis to confirm the role of AEG-1 in clinical outcomes of gastrointestinal carcinoma patients. METHODS: We performed a comprehensive search in PubMed, ISI Web of Science, Cochrane Central Register of Controlled Trials, EMBASE, Science Direct, Wiley Online Library, China National Knowledge Infrastructure (CNKI), WanFang and Chinese VIP databases. STATA 12.0 (STATA Corp., College, TX) was used to analyze the data extracted from suitable studies and Newcastle-Ottawa Scale was applied to assess the quality of included articles. RESULTS: The current meta-analysis included 2999 patients and our results suggested that strong associations emerged between AEG-1 SI and histological differentiation (OR = 2.129, 95%CI: 1.377-3.290, P = 0.001), tumor (T) classification (OR = 2.272, 95%CI: 1.147-4.502, P = 0.019), lymph node (N) classification (OR = 2.696, 95%CI: 2.178-3.337, P<0.001) and metastasis (M) classification (OR = 3.731, 95%CI: 2.167-6.426, P<0.001). Furthermore, high AEG-1 SI was significantly associated with poor overall survival (OS) (HR = 2.369, 95%CI: 2.005-2.800, P<0.001) and deteriorated disease-free survival (DFS) (HR = 1.538, 95%CI: 1.171-2.020, P = 0.002). For disease-specific survival (DSS) and relapse-free survival (RFS), no statistically significant results were observed (HR = 1.573, 95%CI: 0.761-3.250, P = 0.222; HR = 1.432, 95%CI: 0.108-19.085, P = 0.786). Subgroup analysis demonstrated that high AEG-1 SI was significantly related to poor prognosis in esophageal squamous cell carcinoma (ESCC) (HR = 1.715, 95%CI: 1.211-2.410, P = 0.002), gastric carcinoma (GC) (HR = 2.255, 95%CI: 1.547-3.288, P<0.001), colorectal carcinoma (CRC) (HR = 2.922, 95%CI: 1.921-4.444, P<0.001), gallbladder carcinoma (GBC) (HR = 3.047, 95%CI: 1.685-5.509, P<0.001), hepatocellular carcinoma (HCC) (HR = 2.245, 95%CI: 1.620-3.113, P<0.001), pancreatic adenocarcinoma (PAC) (HR = 2.408, 95%CI: 1.625-3.568, P<0.001). CONCLUSIONS: The current meta-analysis indicated that high AEG-1 SI might be associated with tumor progression and poor survival status in patients with gastrointestinal cancer. AEG-1 might play a vital role in promoting tumor aggression and could serve as a potential target for molecular treatments. Further clinical trials are needed to validate whether AEG-1 SI provides valuable insights into improving treatment decisions. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radiofrequency ablation treatment primary intrahepatic cholangiocarcinoma objective present results percutaneous radiofrequency ablation rfa patients unresectable primary intrahepatic cholangiocarcinoma materials methods 2000 2009 13 patients 17 primary intrahepatic cholangiocarcinomas underwent rfa institution intrahepatic cholangiocarcinoma unresectable poor hepatic reserve due liver cirrhosis nine patients extrahepatic extension two atrophy left hepatic lobe one underlying comorbidities one ten tumors diameter less 3 cm five 3 5 cm two larger 5 cm technical effectiveness defined complete ablation tumor shown imaging follow 1 month later local progression free survival overall survival periods complications rfa also evaluated results technical effectiveness rfa achieved 15 17 tumors 88 smaller 5 cm diameter treatment failure occurred two patients large tumors 7 8 cm 17 rfa sessions one major complication 6 liver abscess occurred 1 month later follow median 19 5 months range 3 3 82 1 months nine patients died four remain alive median local progression free survival overall survival periods 32 2 38 5 months respectively 1 3 5 year survival rates 85 51 15 respectively conclusion rfa may provide successful local tumor control patients primary intrahepatic cholangiocarcinomas intermediate 3 5 cm small 3 cm diameter rfa unresectable primary intrahepatic cholangiocarcinoma resulted median overall survival period 38 5 months pubmed","probabilities":0.9799733,"Title":"Radiofrequency ablation for the treatment of primary intrahepatic cholangiocarcinoma","Abstract":"OBJECTIVE: We present the results of percutaneous radiofrequency ablation (RFA) in patients with unresectable primary intrahepatic cholangiocarcinoma. MATERIALS AND METHODS: From 2000 to 2009, 13 patients with 17 primary intrahepatic cholangiocarcinomas underwent RFA at our institution. Intrahepatic cholangiocarcinoma was unresectable because of poor hepatic reserve due to liver cirrhosis in nine patients, extrahepatic extension in two, atrophy of the left hepatic lobe in one, and underlying comorbidities in one. Ten tumors had a diameter of less than 3 cm, five were between 3 and 5 cm, and two were larger than 5 cm. Technical effectiveness was defined as the complete ablation of the tumor, shown by imaging follow-up 1 month later. Local progression-free survival, overall survival periods, and complications after RFA were also evaluated. RESULTS: Technical effectiveness of RFA was achieved for 15 of the 17 tumors (88%), all smaller than 5 cm in diameter. Treatment failure occurred in two patients with large tumors (7 and 8 cm). After the 17 RFA sessions, one major complication (6%), a liver abscess, occurred 1 month later. During follow-up (median, 19.5 months; range, 3.3-82.1 months), nine patients died and four remain alive. Median local progression-free survival and overall survival periods were 32.2 and 38.5 months, respectively. The 1-, 3-, and 5-year survival rates were 85%, 51%, and 15%, respectively. CONCLUSION: RFA may provide successful local tumor control in patients with primary intrahepatic cholangiocarcinomas of intermediate (3-5 cm) or small (< 3 cm) diameter. RFA for unresectable primary intrahepatic cholangiocarcinoma resulted in a median overall survival period of 38.5 months.","Source":"PubMed","category":"HUMAN","training_data":"Radiofrequency ablation for the treatment of primary intrahepatic cholangiocarcinoma OBJECTIVE: We present the results of percutaneous radiofrequency ablation (RFA) in patients with unresectable primary intrahepatic cholangiocarcinoma. MATERIALS AND METHODS: From 2000 to 2009, 13 patients with 17 primary intrahepatic cholangiocarcinomas underwent RFA at our institution. Intrahepatic cholangiocarcinoma was unresectable because of poor hepatic reserve due to liver cirrhosis in nine patients, extrahepatic extension in two, atrophy of the left hepatic lobe in one, and underlying comorbidities in one. Ten tumors had a diameter of less than 3 cm, five were between 3 and 5 cm, and two were larger than 5 cm. Technical effectiveness was defined as the complete ablation of the tumor, shown by imaging follow-up 1 month later. Local progression-free survival, overall survival periods, and complications after RFA were also evaluated. RESULTS: Technical effectiveness of RFA was achieved for 15 of the 17 tumors (88%), all smaller than 5 cm in diameter. Treatment failure occurred in two patients with large tumors (7 and 8 cm). After the 17 RFA sessions, one major complication (6%), a liver abscess, occurred 1 month later. During follow-up (median, 19.5 months; range, 3.3-82.1 months), nine patients died and four remain alive. Median local progression-free survival and overall survival periods were 32.2 and 38.5 months, respectively. The 1-, 3-, and 5-year survival rates were 85%, 51%, and 15%, respectively. CONCLUSION: RFA may provide successful local tumor control in patients with primary intrahepatic cholangiocarcinomas of intermediate (3-5 cm) or small (< 3 cm) diameter. RFA for unresectable primary intrahepatic cholangiocarcinoma resulted in a median overall survival period of 38.5 months. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prediction carcinoma resection subjects ampullary adenomas endoscopic biopsy background goals endoscopic treatment ampullary adenomas established however false negative rate endoscopic biopsy carcinoma 20 30 remains uncertain whether identifiable features predict malignancy aim study evaluate predictable factors malignancy ampullary adenomas endoscopic biopsy study ninety one subjects diagnosed ampullary adenoma endoscopic biopsy confirmed endoscopic surgical resection ampullary lesions 1995 2011 respectively clinical laboratory radiologic endoscopic findings compared patients adenoma carcinoma resection examined predictors malignancy ampullary adenoma endoscopic biopsy results malignancy rate ampullary adenomas endoscopic biopsy 26 4 univariate analysis revealed presence symptoms villous components high grade dysplasia hgd papilla enlargement computed tomography duct dilatation radiologic imaging bilirubin 2 mg dl aspartate aminotransferase 40 iu l alanine aminotransferase 40 iu l alkaline phosphatase 90 u l associated malignancy patients 65 years age hgd odds ratio 6 86 95 confidence interval 1 58 29 79 ductal dilatation odds ratio 11 12 95 confidence interval 2 27 54 37 independently associated malignancy multivariate analysis sensitivity negative predictive value 1 risk factors 95 83 96 77 respectively presence 2 risk factors resulted high specificity 96 positive predictive value 84 malignancy conclusions hgd ductal dilatation significant predictors malignancy ampullary adenomas risk factors present precautions taken consideration malignancy patients ampullary adenoma stn","probabilities":0.9799733,"Title":"Prediction Of Carcinoma After Resection In Subjects With Ampullary Adenomas On Endoscopic Biopsy","Abstract":"Background/goals: The endoscopic treatment of ampullary adenomas is established; however, the false-negative rate of endoscopic biopsy for carcinoma is 20% to 30%, and it remains uncertain whether identifiable features predict malignancy. Our aim in this study was to evaluate the predictable factors of malignancy in ampullary adenomas on endoscopic biopsy. \r\n\r\n Study: Ninety-one subjects diagnosed with ampullary adenoma on endoscopic biopsy were confirmed after endoscopic or surgical resection of ampullary lesions between 1995 and 2011 respectively. Clinical, laboratory, radiologic, and endoscopic findings were compared between patients with adenoma and carcinoma after resection. We examined the predictors of malignancy in ampullary adenoma on endoscopic biopsy. \r\n\r\n Results: The malignancy rate in ampullary adenomas on endoscopic biopsy was 26.4%. Univariate analysis revealed that presence of symptoms, villous components, high-grade dysplasia (HGD), papilla enlargement on computed tomography, duct dilatation on radiologic imaging, bilirubin>2 mg/dL, aspartate aminotransferase>40 IU/L, alanine aminotransferase>40 IU/L, and alkaline phosphatase>90 U/L were associated with malignancy in patients over 65 years of age. HGD [odds ratio, 6.86 (95% confidence interval, 1.58-29.79)] and ductal dilatation [odds ratio, 11.12 (95% confidence interval, 2.27-54.37)] were independently associated with malignancy in multivariate analysis. The sensitivity and negative predictive value for ≥1 risk factors were 95.83% and 96.77%, respectively. The presence of 2 risk factors resulted in a high specificity (96%) and positive predictive value (84%) for malignancy. \r\n\r\n Conclusions: HGD and ductal dilatation are significant predictors of malignancy in ampullary adenomas. When these risk factors are present, precautions should be taken in the consideration of malignancy in patients with ampullary adenoma.","Source":"STN","category":"HUMAN","training_data":"Prediction Of Carcinoma After Resection In Subjects With Ampullary Adenomas On Endoscopic Biopsy Background/goals: The endoscopic treatment of ampullary adenomas is established; however, the false-negative rate of endoscopic biopsy for carcinoma is 20% to 30%, and it remains uncertain whether identifiable features predict malignancy. Our aim in this study was to evaluate the predictable factors of malignancy in ampullary adenomas on endoscopic biopsy. \r\n\r\n Study: Ninety-one subjects diagnosed with ampullary adenoma on endoscopic biopsy were confirmed after endoscopic or surgical resection of ampullary lesions between 1995 and 2011 respectively. Clinical, laboratory, radiologic, and endoscopic findings were compared between patients with adenoma and carcinoma after resection. We examined the predictors of malignancy in ampullary adenoma on endoscopic biopsy. \r\n\r\n Results: The malignancy rate in ampullary adenomas on endoscopic biopsy was 26.4%. Univariate analysis revealed that presence of symptoms, villous components, high-grade dysplasia (HGD), papilla enlargement on computed tomography, duct dilatation on radiologic imaging, bilirubin>2 mg/dL, aspartate aminotransferase>40 IU/L, alanine aminotransferase>40 IU/L, and alkaline phosphatase>90 U/L were associated with malignancy in patients over 65 years of age. HGD [odds ratio, 6.86 (95% confidence interval, 1.58-29.79)] and ductal dilatation [odds ratio, 11.12 (95% confidence interval, 2.27-54.37)] were independently associated with malignancy in multivariate analysis. The sensitivity and negative predictive value for ≥1 risk factors were 95.83% and 96.77%, respectively. The presence of 2 risk factors resulted in a high specificity (96%) and positive predictive value (84%) for malignancy. \r\n\r\n Conclusions: HGD and ductal dilatation are significant predictors of malignancy in ampullary adenomas. When these risk factors are present, precautions should be taken in the consideration of malignancy in patients with ampullary adenoma. STN","prediction_labels":"HUMAN"},{"cleaned":"photodynamic therapy unresectable cholangiocarcinoma nine years american experience background aims photodynamic therapy pdt unresectable cholangiocarcinoma associated improved survival report single tertiary care center experience past 6 years methods fifty five patients unresectable cholangiocarcinoma received pdt 2004 2010 plastic stents placed pdt prevent cholangitis results twenty seven patients 49 showed bismuth type iv 22 41 showed bismuth type iii six 10 showed bismuth type ii twenty patients 37 received chemotherapy radiation therapy five 9 received chemotherapy one 2 received radiation therapy mean number pdt sessions 1 9 1 5 sessions range 1 9 mean survival duration 293 266 days median 190 range 25 1 332 pdt related complications included three 5 facial burn three 5 photosensitivity two 3 rash kaplan meier analysis comparing survival means patients received pdt chemotherapy radiation therapy median survival 257 days 95 confidence interval ci 166 528 versus received pdt median survival 183 days 95 ci 129 224 showed significant difference log rank p 0 20 conclusions pdt measurable impact survival unresectable cholangiocarcinoma requires aggressive stenting posttherapy google scholar","probabilities":0.9799733,"Title":"Photodynamic Therapy In Unresectable Cholangiocarcinoma: Nine Years American Experience","Abstract":"Background/Aims\nPhotodynamic therapy (PDT) in unresectable cholangiocarcinoma has been associated with improved survival. We report a single tertiary care center experience over the past 6 years.\nMethods\nFifty-five patients with unresectable cholangiocarcinoma received PDT between 2004 and 2010. Plastic stents were placed after PDT to prevent cholangitis.\nResults\nTwenty-seven patients (49%) showed Bismuth type IV, 22 (41%) showed Bismuth type III, and six (10%) showed Bismuth type I and II. Twenty patients (37%) received chemotherapy and radiation therapy, five (9%) received chemotherapy only; and one (2%) received radiation therapy only. Mean number of PDT sessions was 1.9±1.5 sessions (range, 1 to 9). Mean survival duration was 293±266 days (median, 190; range, 25 to 1,332). PDT related complications included three (5%) facial burn, three (5%) photosensitivity, and two (3%) rash. Kaplan-Meier analysis comparing the survival means of patients who received PDT and chemotherapy/radiation therapy (median survival 257 days; 95% confidence interval [CI], 166 to 528) versus who received PDT only (median survival 183 days; 95% CI, 129 to 224) showed no significant difference (log-rank p=0.20).\nConclusions\nPDT has a measurable impact on survival in unresectable cholangiocarcinoma but requires aggressive stenting posttherapy.","Source":"Google Scholar","category":"HUMAN","training_data":"Photodynamic Therapy In Unresectable Cholangiocarcinoma: Nine Years American Experience Background/Aims\nPhotodynamic therapy (PDT) in unresectable cholangiocarcinoma has been associated with improved survival. We report a single tertiary care center experience over the past 6 years.\nMethods\nFifty-five patients with unresectable cholangiocarcinoma received PDT between 2004 and 2010. Plastic stents were placed after PDT to prevent cholangitis.\nResults\nTwenty-seven patients (49%) showed Bismuth type IV, 22 (41%) showed Bismuth type III, and six (10%) showed Bismuth type I and II. Twenty patients (37%) received chemotherapy and radiation therapy, five (9%) received chemotherapy only; and one (2%) received radiation therapy only. Mean number of PDT sessions was 1.9±1.5 sessions (range, 1 to 9). Mean survival duration was 293±266 days (median, 190; range, 25 to 1,332). PDT related complications included three (5%) facial burn, three (5%) photosensitivity, and two (3%) rash. Kaplan-Meier analysis comparing the survival means of patients who received PDT and chemotherapy/radiation therapy (median survival 257 days; 95% confidence interval [CI], 166 to 528) versus who received PDT only (median survival 183 days; 95% CI, 129 to 224) showed no significant difference (log-rank p=0.20).\nConclusions\nPDT has a measurable impact on survival in unresectable cholangiocarcinoma but requires aggressive stenting posttherapy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"suppression p53 potentiates chemosensitivity nutrient deprived cholangiocarcinoma cells via inhibition autophagy tumor protein p53 intensively studied major tumor suppressor activation p53 associated various anti neoplastic functions including cell senescence cell cycle arrest apoptosis inhibition angiogenesis however role p53 cancer cell chemosensitivity remains unknown cholangiocarcinoma cell lines qbc939 rbe grown full nutrient nutrient deprived conditions cell lines treated 5 fluorouracil cisplatin rate cell death determined controls using cell counting kit 8 microscopy based methods including presence autophagy inhibitor 3ma p53 inhibitor pft sirna p53 beclin 1 present study demonstrated inhibition p53 enhanced sensitivity chemotherapeutic agents nutrient deprived cholangiocarcinoma cells nutrient deprivation induced autophagy revealed inhibited following inhibition p53 data indicate p53 important activation autophagy nutrient deprived cholangiocarcinoma cells thus contributes cell survival chemoresistance stn","probabilities":0.9467213,"Title":"Suppression Of P53 Potentiates Chemosensitivity In Nutrient-Deprived Cholangiocarcinoma Cells Via Inhibition Of Autophagy","Abstract":"Tumor protein p53 has been intensively studied as a major tumor suppressor. The activation of p53 is associated with various anti-neoplastic functions, including cell senescence, cell cycle arrest, apoptosis and inhibition of angiogenesis. However, the role of p53 in cancer cell chemosensitivity remains unknown. Cholangiocarcinoma cell lines QBC939 and RBE were grown in full-nutrient and nutrient-deprived conditions. The cell lines were treated with 5-fluorouracil or cisplatin and the rate of cell death was determined in these and controls using Cell Counting Kit-8 and microscopy-based methods, including in the presence of autophagy inhibitor 3MA, p53 inhibitor PFT-α or siRNA against p53 or Beclin-1. The present study demonstrated that the inhibition of p53 enhanced the sensitivity to chemotherapeutic agents in nutrient-deprived cholangiocarcinoma cells. Nutrient deprivation-induced autophagy was revealed to be inhibited following inhibition of p53. These data indicate that p53 is important for the activation of autophagy in nutrient-deprived cholangiocarcinoma cells, and thus contributes to cell survival and chemoresistance.","Source":"STN","category":"ANIMAL","training_data":"Suppression Of P53 Potentiates Chemosensitivity In Nutrient-Deprived Cholangiocarcinoma Cells Via Inhibition Of Autophagy Tumor protein p53 has been intensively studied as a major tumor suppressor. The activation of p53 is associated with various anti-neoplastic functions, including cell senescence, cell cycle arrest, apoptosis and inhibition of angiogenesis. However, the role of p53 in cancer cell chemosensitivity remains unknown. Cholangiocarcinoma cell lines QBC939 and RBE were grown in full-nutrient and nutrient-deprived conditions. The cell lines were treated with 5-fluorouracil or cisplatin and the rate of cell death was determined in these and controls using Cell Counting Kit-8 and microscopy-based methods, including in the presence of autophagy inhibitor 3MA, p53 inhibitor PFT-α or siRNA against p53 or Beclin-1. The present study demonstrated that the inhibition of p53 enhanced the sensitivity to chemotherapeutic agents in nutrient-deprived cholangiocarcinoma cells. Nutrient deprivation-induced autophagy was revealed to be inhibited following inhibition of p53. These data indicate that p53 is important for the activation of autophagy in nutrient-deprived cholangiocarcinoma cells, and thus contributes to cell survival and chemoresistance. STN","prediction_labels":"ANIMAL"},{"cleaned":"chemoembolization drug eluting beads preloaded irinotecan debiri vs doxorubicin debdox second line treatment liver metastases cholangiocarcinoma preliminary study objective aim preliminary study compare efficacy drug eluting beads preloaded irinotecan debiri vs drug eluting beads preloaded doxorubicin debdox second line treatment unresectable liver metastases cholangiocarcinoma cca methods 2013 10 patients affected multiple liver metastases cca resistant first line chemotherapy regimen enrolled 5 patients submitted lobar segmental transarterial chemoembolization tace debiri 100 mg irinotecan 1 vial 5 patients debdox 50 mg doxorubicin 1 vial performed every 3 weeks patients treated debiri received antipain premedication consisting 30 mg morphine 3 4 ml intra arterial lidocaine complications efficacy assessed response evaluation criteria solid tumour 1 1 results total 32 tace performed mean 3 2 tace patient well tolerated 1 case asymptomatic cholecystitis spontaneously recovered response rates patients treated debdox debiri 4 5 progressive disease 1 5 partial response vs 2 5 partial response 2 5 stable disease 1 5 progressive disease respectively appearance variable necrosis percentage progression free survival first procedure progressive disease 12 67 weeks debiri 15 78 weeks debdox respectively overall survival time primary diagnosis 176 weeks debiri 125 weeks debdox respectively conclusion preliminary experience debiri effective debdox second line treatment hepatic metastases cca antipain drug administration use microcatheter led good treatment tolerability low complication rate advances knowledge preliminary experience debiri effective debdox second line treatment hepatic metastases cca studies involving larger cohort patients needed pubmed","probabilities":0.9799733,"Title":"Chemoembolization with drug eluting beads preloaded with irinotecan (DEBIRI) vs doxorubicin (DEBDOX) as a second line treatment for liver metastases from cholangiocarcinoma: a preliminary study","Abstract":"OBJECTIVE: The aim of our preliminary study was to compare the efficacy of drug-eluting beads preloaded with irinotecan (DEBIRI) vs drug-eluting beads preloaded with doxorubicin (DEBDOX) as second-line treatment of unresectable liver metastases from cholangiocarcinoma (CCA). METHODS: In 2013, 10 patients affected by multiple liver metastases from CCA, resistant to the first-line chemotherapy regimen, were enrolled: 5 patients were submitted to lobar/segmental transarterial chemoembolization (TACE) with DEBIRI (100-mg irinotecan/1 vial) and 5 patients with DEBDOX (50-mg doxorubicin/1 vial), performed every 3 weeks. Patients treated with DEBIRI received antipain premedication consisting of 30-mg of morphine and 3-4 ml of intra-arterial lidocaine. Complications and efficacy were assessed (response evaluation criteria in solid tumour 1.1). RESULTS: A total of 32 TACE were performed (mean: 3.2 TACE/patient), all well tolerated, with only 1 case of asymptomatic cholecystitis spontaneously recovered. Response rates of patients treated with DEBDOX and DEBIRI were: 4/5 progressive disease and 1/5 partial response vs 2/5 partial response, 2/5 stable disease and 1/5 progressive disease, respectively, with the appearance of variable necrosis percentage. Progression-free survival from the first procedure and progressive disease were 12.67 weeks for DEBIRI and 15.78 weeks for DEBDOX, respectively. Overall survival from time of primary diagnosis was 176 weeks for DEBIRI and 125 weeks for DEBDOX, respectively. CONCLUSION: In our preliminary experience, DEBIRI was more effective than DEBDOX as a second-line treatment for hepatic metastases from CCA. Antipain drug administration and the use of the microcatheter led to a good treatment tolerability and a low complication rate. Advances in knowledge: In our preliminary experience, DEBIRI was more effective than DEBDOX as a second-line treatment of hepatic metastases from CCA; further studies involving a larger cohort of patients are needed.","Source":"PubMed","category":"HUMAN","training_data":"Chemoembolization with drug eluting beads preloaded with irinotecan (DEBIRI) vs doxorubicin (DEBDOX) as a second line treatment for liver metastases from cholangiocarcinoma: a preliminary study OBJECTIVE: The aim of our preliminary study was to compare the efficacy of drug-eluting beads preloaded with irinotecan (DEBIRI) vs drug-eluting beads preloaded with doxorubicin (DEBDOX) as second-line treatment of unresectable liver metastases from cholangiocarcinoma (CCA). METHODS: In 2013, 10 patients affected by multiple liver metastases from CCA, resistant to the first-line chemotherapy regimen, were enrolled: 5 patients were submitted to lobar/segmental transarterial chemoembolization (TACE) with DEBIRI (100-mg irinotecan/1 vial) and 5 patients with DEBDOX (50-mg doxorubicin/1 vial), performed every 3 weeks. Patients treated with DEBIRI received antipain premedication consisting of 30-mg of morphine and 3-4 ml of intra-arterial lidocaine. Complications and efficacy were assessed (response evaluation criteria in solid tumour 1.1). RESULTS: A total of 32 TACE were performed (mean: 3.2 TACE/patient), all well tolerated, with only 1 case of asymptomatic cholecystitis spontaneously recovered. Response rates of patients treated with DEBDOX and DEBIRI were: 4/5 progressive disease and 1/5 partial response vs 2/5 partial response, 2/5 stable disease and 1/5 progressive disease, respectively, with the appearance of variable necrosis percentage. Progression-free survival from the first procedure and progressive disease were 12.67 weeks for DEBIRI and 15.78 weeks for DEBDOX, respectively. Overall survival from time of primary diagnosis was 176 weeks for DEBIRI and 125 weeks for DEBDOX, respectively. CONCLUSION: In our preliminary experience, DEBIRI was more effective than DEBDOX as a second-line treatment for hepatic metastases from CCA. Antipain drug administration and the use of the microcatheter led to a good treatment tolerability and a low complication rate. Advances in knowledge: In our preliminary experience, DEBIRI was more effective than DEBDOX as a second-line treatment of hepatic metastases from CCA; further studies involving a larger cohort of patients are needed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatitis b virus infection increases risk cholangiocarcinoma meta analysis systematic review background aim number studies shown hepatitis virus infections may associated cholangiocarcinoma cc however relationship hepatitis b virus hbv infection cc especially intrahepatic cholangiocarcinoma icc still controversial methods relevant studies identified searching pubmed embase web science datebases september 2011 pooled risk estimates calculated using random effects model potential sources heterogeneity performed subgroup analyses total 18 papers included meta analysis results pooled risk estimate studies showed statistically significant increased risk cc among individuals hbv infection rate ratio rr 2 66 95 confidence interval ci 1 97 3 60 compared without hbv infection persons hbv infection increased risk intra cc icc rr 3 42 95 ci 2 46 43 74 extrahepatic cc 1 46 95 ci 0 98 2 17 cc 2 03 95 ci 1 15 3 56 subgroup analysis hbv infection risk icc pooled risk estimate studies asians rr 3 63 95 ci 2 56 5 13 higher non asians rr 1 93 95 ci 0 78 4 76 begg funnel plot egger test revealed evidence publication bias conclusions meta analysis shows hbv associated increased risk cc especially icc investigation needed focus mechanism hbv may involved pathogenesis cc pubmed","probabilities":0.9799733,"Title":"Hepatitis B virus infection increases the risk of cholangiocarcinoma: a meta-analysis and systematic review","Abstract":"BACKGROUND AND AIM: A number of studies have shown that hepatitis virus infections may be associated with cholangiocarcinoma (CC). However, the relationship between hepatitis B virus (HBV) infection and CC, especially intrahepatic cholangiocarcinoma (ICC), is still controversial. METHODS: Relevant studies were identified by searching PUBMED, EMBASE and Web of Science Datebases up to September 2011. Pooled risk estimates were calculated using a random-effects model. Potential sources of heterogeneity were performed by subgroup analyses. A total of 18 papers were included in this meta-analysis. RESULTS: The pooled risk estimate of all studies showed a statistically significant increased risk of CC among individuals with HBV infection (rate ratio [RR]: 2.66; 95% confidence interval [CI]: 1.97, 3.60). Compared with those without HBV infection, persons with HBV infection had an increased risk of intra-CC (ICC) (RR: 3.42; 95% CI: 2.46, 43.74), extrahepatic CC (OR: 1.46; 95% CI: 0.98, 2.17), and CC (OR: 2.03; 95% CI: 1.15, 3.56). In a subgroup analysis of HBV infection and risk of ICC, the pooled risk estimate of studies in Asians (RR: 3.63; 95% CI: 2.56, 5.13) was higher than that in non-Asians (RR: 1.93; 95% CI: 0.78, 4.76). A Begg funnel plot and Egger test revealed no evidence for publication bias. CONCLUSIONS: This meta-analysis shows that HBV is associated with increased risk of CC, especially for ICC. Further investigation is needed to focus on the mechanism by which HBV may be involved in the pathogenesis of CC.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis B virus infection increases the risk of cholangiocarcinoma: a meta-analysis and systematic review BACKGROUND AND AIM: A number of studies have shown that hepatitis virus infections may be associated with cholangiocarcinoma (CC). However, the relationship between hepatitis B virus (HBV) infection and CC, especially intrahepatic cholangiocarcinoma (ICC), is still controversial. METHODS: Relevant studies were identified by searching PUBMED, EMBASE and Web of Science Datebases up to September 2011. Pooled risk estimates were calculated using a random-effects model. Potential sources of heterogeneity were performed by subgroup analyses. A total of 18 papers were included in this meta-analysis. RESULTS: The pooled risk estimate of all studies showed a statistically significant increased risk of CC among individuals with HBV infection (rate ratio [RR]: 2.66; 95% confidence interval [CI]: 1.97, 3.60). Compared with those without HBV infection, persons with HBV infection had an increased risk of intra-CC (ICC) (RR: 3.42; 95% CI: 2.46, 43.74), extrahepatic CC (OR: 1.46; 95% CI: 0.98, 2.17), and CC (OR: 2.03; 95% CI: 1.15, 3.56). In a subgroup analysis of HBV infection and risk of ICC, the pooled risk estimate of studies in Asians (RR: 3.63; 95% CI: 2.56, 5.13) was higher than that in non-Asians (RR: 1.93; 95% CI: 0.78, 4.76). A Begg funnel plot and Egger test revealed no evidence for publication bias. CONCLUSIONS: This meta-analysis shows that HBV is associated with increased risk of CC, especially for ICC. Further investigation is needed to focus on the mechanism by which HBV may be involved in the pathogenesis of CC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value trop2 expression patients gallbladder cancer altered expression trop2 observed various types human cancers however clinical significance pathological role trop2 gallbladder cancer gbc remains unclear main objective investigation clarify relationships trop2 expression clinicopathological features patients gbc immunohistochemistry performed investigate expression trop2 epithelial mesenchymal transition emt indicator proteins 93 patients gbc immunohistochemistry showed protein expression level trop2 significantly higher gbc tissues adjacent noncancerous tissues addition immunohistochemistry analysis showed trop2 expression significantly correlated histologic grade p 0 038 tumor stage p 0 015 lymph node metastasis p 0 007 furthermore high trop2 expression significantly associated loss epithelial marker e cadherin p 0 013 acquisition expression mesenchymal marker vimentin p 0 031 kaplan meier analysis cox proportional hazards regression models used investigate correlation trop2 expression prognosis gbc patients kaplan meier analysis indicated patients high trop2 expression poor overall survival p 0 001 multivariate analysis showed high trop2 expression independent predictor overall survival conclusion data suggest first time increased expression trop2 gbc associated significantly aggressive progression poor prognosis conclusion study confirmed trop2 might involved regulating emt malignant progression gbc also provided first evidence trop2 expression gbc independent prognostic factor patients might potential diagnostic therapeutic target gbc pubmed","probabilities":0.8684211,"Title":"Prognostic value of TROP2 expression in patients with gallbladder cancer","Abstract":"Altered expression of TROP2 is observed in various types of human cancers. However, the clinical significance and pathological role of TROP2 in gallbladder cancer (GBC) remains unclear. The main objective of this investigation was to clarify the relationships between TROP2 expression and the clinicopathological features of patients with GBC. Immunohistochemistry was performed to investigate the expression of TROP2 and epithelial-mesenchymal transition (EMT) indicator proteins in 93 patients with GBC. Immunohistochemistry showed that the protein expression level of TROP2 was significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that TROP2 expression was significantly correlated with histologic grade (P=0.038), tumor stage (P=0.015), and lymph node metastasis (P=0.007). Furthermore, high TROP2 expression was significantly associated with a loss of the epithelial marker E-cadherin (P=0.013) and acquisition of expression of the mesenchymal marker vimentin (P=0.031). Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between TROP2 expression and prognosis of GBC patients. Kaplan-Meier analysis indicated that patients with high TROP2 expression had poor overall survival (P<0.001). Multivariate analysis showed that high TROP2 expression was an independent predictor of overall survival. In conclusion, our data suggest for the first time that the increased expression of TROP2 in GBC is associated significantly with aggressive progression and poor prognosis. In conclusion, this study confirmed that TROP2 might be involved in regulating the EMT and malignant progression in GBC. It also provided the first evidence that TROP2 expression in GBC was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of GBC.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic value of TROP2 expression in patients with gallbladder cancer Altered expression of TROP2 is observed in various types of human cancers. However, the clinical significance and pathological role of TROP2 in gallbladder cancer (GBC) remains unclear. The main objective of this investigation was to clarify the relationships between TROP2 expression and the clinicopathological features of patients with GBC. Immunohistochemistry was performed to investigate the expression of TROP2 and epithelial-mesenchymal transition (EMT) indicator proteins in 93 patients with GBC. Immunohistochemistry showed that the protein expression level of TROP2 was significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that TROP2 expression was significantly correlated with histologic grade (P=0.038), tumor stage (P=0.015), and lymph node metastasis (P=0.007). Furthermore, high TROP2 expression was significantly associated with a loss of the epithelial marker E-cadherin (P=0.013) and acquisition of expression of the mesenchymal marker vimentin (P=0.031). Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between TROP2 expression and prognosis of GBC patients. Kaplan-Meier analysis indicated that patients with high TROP2 expression had poor overall survival (P<0.001). Multivariate analysis showed that high TROP2 expression was an independent predictor of overall survival. In conclusion, our data suggest for the first time that the increased expression of TROP2 in GBC is associated significantly with aggressive progression and poor prognosis. In conclusion, this study confirmed that TROP2 might be involved in regulating the EMT and malignant progression in GBC. It also provided the first evidence that TROP2 expression in GBC was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"novel three mirna signature predicts survival cholangiocarcinoma based rna seq data accumulating evidence illustrates many micrornas mirnas abnormally expressed cholangiocarcinoma play important roles tumorigenesis tumor progression metastasis mirnas may serve prognostic biomarkers potential therapeutic targets aim present study identify differentially expressed mirnas cholangiocarcinoma tissues vs normal tissues analyzing high throughput data derived cancer genome atlas tcga database furthermore evaluated prognostic performance differentially expressed mirnas developed novel three mirna signature predicted survival cholangiocarcinoma patients according cut criteria p 0 01 log2fc 1 0 total 100 mirnas 54 upregulated 46 downregulated found differentially expressed significantly associated clinical features 100 mirnas obtained three mirnas mir 10b mir 22 mir 551b markedly related patient overall survival os subsequently novel three mirna signature established validated effective predict survival results demonstrated survival rate well survival time patients obviously enhanced relation lower mirna signature index univariate multivariate cox regression analyses revealed three mirna signature independent prognostic factor cholangiocarcinoma reliability three mirna signature validated independent cohort gene expression omnibus geo furthermore functional enrichment analysis emphasized target genes aforementioned mirnas may involved variety pathways processes associated cancer finally three mirnas detected verification expression using rt qpcr mir 551b selected verification biological functions cholangiocarcinoma cells results revealed overexpression mir 551b decreased cancer cell proliferation promoted apoptosis collectively results present study indicated specific three mirna signature considered alternative prognostic marker cholangiocarcinoma pubmed","probabilities":1.0,"Title":"A novel three‑miRNA signature predicts survival in cholangiocarcinoma based on RNA‑Seq data","Abstract":"Accumulating evidence illustrates that many microRNAs (miRNAs) are abnormally expressed in cholangiocarcinoma and play important roles in tumorigenesis, tumor progression and metastasis. These miRNAs may serve as prognostic biomarkers and potential therapeutic targets. The aim of the present study was to identify the differentially expressed miRNAs in cholangiocarcinoma tissues vs. normal tissues by analyzing high‑throughput data derived from The Cancer Genome Atlas (TCGA) database. Furthermore, we evaluated the prognostic performance of the differentially expressed miRNAs and developed a novel three‑miRNA signature which predicted survival in cholangiocarcinoma patients. According to the cut‑off criteria of P<0.01 and |log2FC|>1.0, a total of 100 miRNAs (54 upregulated and 46 downregulated) were found to be differentially expressed and some of them were significantly associated with clinical features. Of the above 100 miRNAs, we obtained three miRNAs (miR‑10b, miR‑22 and miR‑551b) which were markedly related to patient overall survival (OS). Subsequently, a novel three‑miRNA signature was established and validated to be effective to predict survival. The results demonstrated that the survival rate, as well as the survival time of patients were obviously enhanced in relation to a lower miRNA signature index. Univariate and multivariate Cox regression analyses revealed that the three‑miRNA signature was an independent prognostic factor in cholangiocarcinoma. The reliability of the three‑miRNA signature was validated by an independent cohort from Gene Expression Omnibus (GEO). Furthermore, the functional enrichment analysis emphasized that the target genes of the aforementioned miRNAs may be involved in a variety of pathways and processes associated with cancer. Finally, these three miRNAs were detected for verification of expression using RT‑qPCR, and miR‑551b was selected for the verification of biological functions in cholangiocarcinoma cells. The results revealed that overexpression of miR‑551b decreased cancer cell proliferation and promoted apoptosis. Collectively, the results of the present study indicated that a specific three‑miRNA signature could be considered as an alternative prognostic marker in cholangiocarcinoma.","Source":"PubMed","category":"ANIMAL","training_data":"A novel three‑miRNA signature predicts survival in cholangiocarcinoma based on RNA‑Seq data Accumulating evidence illustrates that many microRNAs (miRNAs) are abnormally expressed in cholangiocarcinoma and play important roles in tumorigenesis, tumor progression and metastasis. These miRNAs may serve as prognostic biomarkers and potential therapeutic targets. The aim of the present study was to identify the differentially expressed miRNAs in cholangiocarcinoma tissues vs. normal tissues by analyzing high‑throughput data derived from The Cancer Genome Atlas (TCGA) database. Furthermore, we evaluated the prognostic performance of the differentially expressed miRNAs and developed a novel three‑miRNA signature which predicted survival in cholangiocarcinoma patients. According to the cut‑off criteria of P<0.01 and |log2FC|>1.0, a total of 100 miRNAs (54 upregulated and 46 downregulated) were found to be differentially expressed and some of them were significantly associated with clinical features. Of the above 100 miRNAs, we obtained three miRNAs (miR‑10b, miR‑22 and miR‑551b) which were markedly related to patient overall survival (OS). Subsequently, a novel three‑miRNA signature was established and validated to be effective to predict survival. The results demonstrated that the survival rate, as well as the survival time of patients were obviously enhanced in relation to a lower miRNA signature index. Univariate and multivariate Cox regression analyses revealed that the three‑miRNA signature was an independent prognostic factor in cholangiocarcinoma. The reliability of the three‑miRNA signature was validated by an independent cohort from Gene Expression Omnibus (GEO). Furthermore, the functional enrichment analysis emphasized that the target genes of the aforementioned miRNAs may be involved in a variety of pathways and processes associated with cancer. Finally, these three miRNAs were detected for verification of expression using RT‑qPCR, and miR‑551b was selected for the verification of biological functions in cholangiocarcinoma cells. The results revealed that overexpression of miR‑551b decreased cancer cell proliferation and promoted apoptosis. Collectively, the results of the present study indicated that a specific three‑miRNA signature could be considered as an alternative prognostic marker in cholangiocarcinoma. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"gallbladder cancer predisposition multigenic approach inflammatory cholesterol metabolizing pathway genes gallbladder cancer gbc multifactorial disease complex interplay multiple genetic variants performed classification regression tree analysis cart grade membership gom analysis identify combinations alleles among dna repair inflammatory apoptotic pathway genetic variants modifying risk gbc analyzed 16 polymorphisms 8 genes involved dna repair apoptotic inflammatory pathways find combinations genetic variants contributing gbc risk genes included study xrcc1 ogg1 ercc2 msh2 casp8 tlr2 tlr4 ptgs2 single locus analysis logistic regression showed association msh2 ivs1 9g c rs2303426 ercc2 asp312asn rs1799793 ogg1 ser326cys rs1052133 ogg1 ivs4 15c g rs2072668 casp8 652 6n ins del rs3834129 ptgs2 1195g rs689466 ptgs2 765g c rs20417 tlr4 ex4 936c rs4986791 tlr2 196 174del polymorphisms gbc risk cart analysis revealed ogg1 ser326cys ogg1 ivs4 15c g polymorphisms best polymorphic signature discriminating cases controls gom analysis data categorized six sets representing risk gbc respect investigated polymorphisms sets ii iii described low intrinsic risk controls characterized multiple protective alleles sets iv v vi represented high intrinsic risk groups gbc cases characterized presence multiple risk alleles cart gom analyses also showed importance ptgs2 1195g polymorphism susceptibility gbc risk conclusion present multigenic approach used define individual risk profiles gallbladder cancer north indian population google scholar","probabilities":0.9799733,"Title":"Gallbladder Cancer Predisposition: A Multigenic Approach To Inflammatory And Cholesterol Metabolizing Pathway Genes","Abstract":"Gallbladder cancer (GBC) is a multifactorial disease with complex interplay between multiple genetic variants. We performed Classification and Regression Tree Analysis (CART) and Grade of Membership (GoM) analysis to identify combinations of alleles among the DNA repair, inflammatory and apoptotic pathway genetic variants in modifying the risk for GBC. We analyzed 16 polymorphisms in 8 genes involved in DNA repair, apoptotic and inflammatory pathways to find out combinations of genetic variants contributing to GBC risk. The genes included in the study were XRCC1, OGG1, ERCC2, MSH2, CASP8, TLR2, TLR4 and PTGS2. Single locus analysis by logistic regression showed association of MSH2 IVS1+9G>C (rs2303426), ERCC2 Asp312Asn (rs1799793), OGG1 Ser326Cys (rs1052133), OGG1 IVS4-15C>G (rs2072668), CASP8 -652 6N ins/del (rs3834129), PTGS2 -1195G>A (rs689466), PTGS2 -765G>C (rs20417), TLR4 Ex4+936C>T (rs4986791) and TLR2 –196 to –174del polymorphisms with GBC risk. The CART analysis revealed OGG1 Ser326Cys, and OGG1 IVS4-15C>G polymorphisms as the best polymorphic signature for discriminating between cases and controls. In the GoM analysis, the data was categorized into six sets representing risk for GBC with respect to the investigated polymorphisms. Sets I, II and III described low intrinsic risk (controls) characterized by multiple protective alleles while sets IV, V and VI represented high intrinsic risk groups (GBC cases) characterized by the presence of multiple risk alleles. The CART and GoM analyses also showed the importance of PTGS2 -1195G>A polymorphism in susceptibility to GBC risk. In conclusion, the present multigenic approach can be used to define individual risk profiles for gallbladder cancer in North Indian population.","Source":"Google Scholar","category":"HUMAN","training_data":"Gallbladder Cancer Predisposition: A Multigenic Approach To Inflammatory And Cholesterol Metabolizing Pathway Genes Gallbladder cancer (GBC) is a multifactorial disease with complex interplay between multiple genetic variants. We performed Classification and Regression Tree Analysis (CART) and Grade of Membership (GoM) analysis to identify combinations of alleles among the DNA repair, inflammatory and apoptotic pathway genetic variants in modifying the risk for GBC. We analyzed 16 polymorphisms in 8 genes involved in DNA repair, apoptotic and inflammatory pathways to find out combinations of genetic variants contributing to GBC risk. The genes included in the study were XRCC1, OGG1, ERCC2, MSH2, CASP8, TLR2, TLR4 and PTGS2. Single locus analysis by logistic regression showed association of MSH2 IVS1+9G>C (rs2303426), ERCC2 Asp312Asn (rs1799793), OGG1 Ser326Cys (rs1052133), OGG1 IVS4-15C>G (rs2072668), CASP8 -652 6N ins/del (rs3834129), PTGS2 -1195G>A (rs689466), PTGS2 -765G>C (rs20417), TLR4 Ex4+936C>T (rs4986791) and TLR2 –196 to –174del polymorphisms with GBC risk. The CART analysis revealed OGG1 Ser326Cys, and OGG1 IVS4-15C>G polymorphisms as the best polymorphic signature for discriminating between cases and controls. In the GoM analysis, the data was categorized into six sets representing risk for GBC with respect to the investigated polymorphisms. Sets I, II and III described low intrinsic risk (controls) characterized by multiple protective alleles while sets IV, V and VI represented high intrinsic risk groups (GBC cases) characterized by the presence of multiple risk alleles. The CART and GoM analyses also showed the importance of PTGS2 -1195G>A polymorphism in susceptibility to GBC risk. In conclusion, the present multigenic approach can be used to define individual risk profiles for gallbladder cancer in North Indian population. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"validation study tumor invasive thickness postoperative prognosis 110 patients underwent pancreatoduodenectomy distal cholangiocarcinoma single institution pt classification 8th american joint committee cancer ajcc distal cholangiocarcinoma dcc classified according depth invasion doi distance basal lamina deeply advanced tumor cells nagoya group proposed new classification dcc based invasive tumor thickness itt maximal vertical distance invasive cancer component itt grade study aimed validate itt grade next pt classification dcc 110 patients itt measured patients doi measured 62 56 patients according itt grade patients classified grades d follows grade itt 1 mm n 9 grade b itt 1 mm 5 mm n 35 grade c itt 5 mm 10 mm n 40 grade d itt 10 mm greater n 26 median overall survival times patients itt grades b c d 12 8 5 7 3 7 2 0 years respectively itt grade discriminate postoperative survivals grades multivariate analysis itt grade regional lymph node metastasis distant metastasis selected independent prognostic factors summary results showed itt grade suitable alternative doi pt classification next edition ajcc dcc pubmed","probabilities":0.9799733,"Title":"Validation Study of Tumor Invasive Thickness for Postoperative Prognosis in 110 Patients Who Underwent Pancreatoduodenectomy for Distal Cholangiocarcinoma at a Single Institution","Abstract":"The pT classification of the 8th American Joint Committee on Cancer (AJCC) for distal cholangiocarcinoma (DCC) is classified according to depth of invasion (DOI), which is the distance from the basal lamina to the most deeply advanced tumor cells. The Nagoya group proposed a new T classification for DCC based on invasive tumor thickness (ITT), which is the maximal vertical distance of the invasive cancer component (the ITT grade). In this study, we aimed to validate the ITT grade for the next pT classification of DCC in 110 patients. ITT could be measured in all patients, but DOI could only be measured in 62 (56%) patients. According to ITT grade, patients were classified into grades A to D, as follows: grade A, ITT <1 mm (n=9); grade B, ITT 1 mm or more but <5 mm (n=35); grade C, ITT 5 mm or more but <10 mm (n=40); and grade D, ITT 10 mm or greater (n=26). The median overall survival times in patients with ITT grades A, B, C, and D were 12.8, 5.7, 3.7, and 2.0 years, respectively. ITT grade could discriminate postoperative survivals between grades. On multivariate analysis, ITT grade, regional lymph node metastasis, and distant metastasis were selected as independent prognostic factors. In summary, our results showed that ITT grade was a suitable alternative to DOI for pT classification in the next edition of the AJCC for DCC.","Source":"PubMed","category":"HUMAN","training_data":"Validation Study of Tumor Invasive Thickness for Postoperative Prognosis in 110 Patients Who Underwent Pancreatoduodenectomy for Distal Cholangiocarcinoma at a Single Institution The pT classification of the 8th American Joint Committee on Cancer (AJCC) for distal cholangiocarcinoma (DCC) is classified according to depth of invasion (DOI), which is the distance from the basal lamina to the most deeply advanced tumor cells. The Nagoya group proposed a new T classification for DCC based on invasive tumor thickness (ITT), which is the maximal vertical distance of the invasive cancer component (the ITT grade). In this study, we aimed to validate the ITT grade for the next pT classification of DCC in 110 patients. ITT could be measured in all patients, but DOI could only be measured in 62 (56%) patients. According to ITT grade, patients were classified into grades A to D, as follows: grade A, ITT <1 mm (n=9); grade B, ITT 1 mm or more but <5 mm (n=35); grade C, ITT 5 mm or more but <10 mm (n=40); and grade D, ITT 10 mm or greater (n=26). The median overall survival times in patients with ITT grades A, B, C, and D were 12.8, 5.7, 3.7, and 2.0 years, respectively. ITT grade could discriminate postoperative survivals between grades. On multivariate analysis, ITT grade, regional lymph node metastasis, and distant metastasis were selected as independent prognostic factors. In summary, our results showed that ITT grade was a suitable alternative to DOI for pT classification in the next edition of the AJCC for DCC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"influence high low volume liver surgery gallbladder carcinoma aim clarify whether performance liver resections lr incidental gallbladder carcinoma igbc depends experience hospitals liver surgery complying guidelines germany methods data analysis used surgical association endoscopy ultrasound minimally invasive surgery central registry igbc german society surgery german registry 2010 started second form requesting frequency lr various hospitals germany indication lr irrelevant aim determine overall frequency liver resections hospitals divided hospitals according experience liver surgery high hv mid mv low volume lv lr hospitals results study includes 487 igbc 167 centers 36 high volume 32 mid volume 99 low volume centers high volume centers mean range number liver resections 101 40 300 mid volume centers mean range number liver resections 26 20 39 low volume centers mean range number liver resections 6 5 0 19 p 0 001 lv perform lr t2 3 gallbladder carcinomas significantly less often high volume mid volume centers 2 13 78 p 0 001 hv mv 61 patients indication liver resection underwent lr lv centers 41 indication lr underwent lr p 0 001 cases t1b carcinomas lr performed significantly often hv p 0 009 conclusion central problem performance required liver resection igbc germany depends hospital experience liver surgery recommendations german guidelines stn","probabilities":0.9799733,"Title":"Influence Of High- And Low-Volume Liver Surgery In Gallbladder Carcinoma","Abstract":"Aim: To clarify whether the performance of liver resections (LR) for incidental gallbladder carcinoma (IGBC)'s depends more on the experience of the hospitals in liver surgery than on complying with the guidelines in Germany. \r\n\r\n Methods: For data analysis, we used the Surgical Association of Endoscopy and Ultrasound and Minimally Invasive Surgery Central Registry of \"IGBC\" of the German Society of Surgery (the German Registry). In 2010, we started a second form by requesting the frequency of LR at the various hospitals in Germany. The indication for LR was irrelevant. The aim was to determine the overall frequency of liver resections at the hospitals. We divided the hospitals according to their experience in liver surgery into high- (HV), mid- (MV), and low-volume (LV) LR hospitals. \r\n\r\n Results: This study includes 487 IGBC's from 167 centers. There were 36 high-volume, 32 mid-volume, and 99 low-volume centers. In the high-volume centers, the mean (range) number of liver resections was 101 (40-300). In the mid-volume centers, the mean (range) number of liver resections was 26 (20-39). In the low-volume centers, the mean (range) number of liver resections was 6.5 (0-19) (P < 0.001). LV's perform LR for T2-3 gallbladder carcinomas significantly less often than high-volume or mid-volume centers (χ(2) = 13.78, P = 0.001). In HV's and MV's, 61% of the patients with an indication for liver resection underwent LR, but in LV centers, only 41% with an indication for LR underwent LR (P < 0.001). In cases of T1b carcinomas, LR was performed significantly more often in HV's (P = 0.009). \r\n\r\n Conclusion: The central problem is that the performance of the required liver resection in IGBC in Germany depends on the hospital experience in liver surgery and not on the recommendations of the German guidelines.","Source":"STN","category":"HUMAN","training_data":"Influence Of High- And Low-Volume Liver Surgery In Gallbladder Carcinoma Aim: To clarify whether the performance of liver resections (LR) for incidental gallbladder carcinoma (IGBC)'s depends more on the experience of the hospitals in liver surgery than on complying with the guidelines in Germany. \r\n\r\n Methods: For data analysis, we used the Surgical Association of Endoscopy and Ultrasound and Minimally Invasive Surgery Central Registry of \"IGBC\" of the German Society of Surgery (the German Registry). In 2010, we started a second form by requesting the frequency of LR at the various hospitals in Germany. The indication for LR was irrelevant. The aim was to determine the overall frequency of liver resections at the hospitals. We divided the hospitals according to their experience in liver surgery into high- (HV), mid- (MV), and low-volume (LV) LR hospitals. \r\n\r\n Results: This study includes 487 IGBC's from 167 centers. There were 36 high-volume, 32 mid-volume, and 99 low-volume centers. In the high-volume centers, the mean (range) number of liver resections was 101 (40-300). In the mid-volume centers, the mean (range) number of liver resections was 26 (20-39). In the low-volume centers, the mean (range) number of liver resections was 6.5 (0-19) (P < 0.001). LV's perform LR for T2-3 gallbladder carcinomas significantly less often than high-volume or mid-volume centers (χ(2) = 13.78, P = 0.001). In HV's and MV's, 61% of the patients with an indication for liver resection underwent LR, but in LV centers, only 41% with an indication for LR underwent LR (P < 0.001). In cases of T1b carcinomas, LR was performed significantly more often in HV's (P = 0.009). \r\n\r\n Conclusion: The central problem is that the performance of the required liver resection in IGBC in Germany depends on the hospital experience in liver surgery and not on the recommendations of the German guidelines. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic role modified glasgow prognostic score patients cholangiocarcinoma meta analysis literature review abstract background aim increasing evidence indicates modified glasgow prognostic score mgps useful biomarker long term outcomes various types cancer however prognostic value patients cholangiocarcinoma fully investigated thus investigated relationship overall survival os evaluate role predicting survival patients cholangiocarcinoma methods pubmed embase web science databases systematically searched identify studies evaluated prognostic impact modified glasgow prognostic score mgps cholangiocarcinoma patients meta analysis using random effects model performed calculate hazard ratio hr corresponding confidence intervals cis respectively results total five studies comprising 1022 patients included meta analysis overall survival used outcome measure results showed os worse patients mgps 1 2 pooled hr 1 80 95 ci 1 48 2 19 p 0 001 score 0 patients mgps 0 1 significantly prolonged os compared score 2 pooled hr 3 89 95 ci 1 708 91 p 0 001 conclusions results meta analysis suggest higher mgps associated poorer survival patients cholangiocarcinoma well designed studies necessary provide solid data confirm prognostic significance mgps google scholar","probabilities":0.9799733,"Title":"Prognostic Role Of Modified Glasgow Prognostic Score In Patients With Cholangiocarcinoma: A Meta-Analysis And Literature Review","Abstract":"Abstract: Background and aim: Increasing evidence indicates that the modified Glasgow Prognostic Score (mGPS) is a useful biomarker of long-term outcomes in various types of cancer. However, its prognostic value in patients with cholangiocarcinoma is not fully investigated. Thus, we investigated its relationship with overall survival (OS) to evaluate its role in predicting survival in patients with cholangiocarcinoma. Methods: PubMed, EMBASE and Web of Science databases were systematically searched to identify studies that evaluated the prognostic impact of the modified Glasgow Prognostic Score (mGPS) in cholangiocarcinoma patients. Meta-analysis using random-effects model was performed to calculate hazard ratio (HR) and corresponding confidence intervals (CIs) respectively. Results: A total of five studies comprising 1022 patients were included in the meta-analysis, of which overall survival was used as an outcome measure. The results showed that OS was worse in patients with a mGPS = 1 or 2 with a pooled HR of 1.80 (95% CI = 1.48-2.19, P<0.001) than those with a score of 0. The patients with a mGPS = 0 or 1 have significantly prolonged OS compared with those with a score of 2 with a pooled HR of 3.89 (95% CI = 1.708.91, P = 0.001). Conclusions: The results of this meta-analysis suggest that higher mGPS is associated with poorer survival in patients with cholangiocarcinoma. More well-designed studies are necessary to provide solid data to confirm the prognostic significance of mGPS.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Role Of Modified Glasgow Prognostic Score In Patients With Cholangiocarcinoma: A Meta-Analysis And Literature Review Abstract: Background and aim: Increasing evidence indicates that the modified Glasgow Prognostic Score (mGPS) is a useful biomarker of long-term outcomes in various types of cancer. However, its prognostic value in patients with cholangiocarcinoma is not fully investigated. Thus, we investigated its relationship with overall survival (OS) to evaluate its role in predicting survival in patients with cholangiocarcinoma. Methods: PubMed, EMBASE and Web of Science databases were systematically searched to identify studies that evaluated the prognostic impact of the modified Glasgow Prognostic Score (mGPS) in cholangiocarcinoma patients. Meta-analysis using random-effects model was performed to calculate hazard ratio (HR) and corresponding confidence intervals (CIs) respectively. Results: A total of five studies comprising 1022 patients were included in the meta-analysis, of which overall survival was used as an outcome measure. The results showed that OS was worse in patients with a mGPS = 1 or 2 with a pooled HR of 1.80 (95% CI = 1.48-2.19, P<0.001) than those with a score of 0. The patients with a mGPS = 0 or 1 have significantly prolonged OS compared with those with a score of 2 with a pooled HR of 3.89 (95% CI = 1.708.91, P = 0.001). Conclusions: The results of this meta-analysis suggest that higher mGPS is associated with poorer survival in patients with cholangiocarcinoma. More well-designed studies are necessary to provide solid data to confirm the prognostic significance of mGPS. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"ercp tissue sampling nan pubmed","probabilities":0.7966102,"Title":"ERCP tissue sampling","Abstract":"NaN","Source":"PubMed","category":"ANIMAL","training_data":"ERCP tissue sampling nan PubMed","prediction_labels":"HUMAN"},{"cleaned":"inhibition carbonic anhydrase potentiates bevacizumab treatment cholangiocarcinoma cholangiocarcinoma cca unique liver cancer subtype increasing incidence globally lack specific symptoms definite diagnostic markers results delayed diagnosis disease progression systemic chemotherapy commonly selected advanced cca even though advantages remain unknown targeted therapy especially anti vascular endothelial growth factor vegf therapy promising cca however improvements therapeutic regimen necessary overcome subsequent resistance demonstrated vegf expression higher cca cell lines liver cancer cells secreted vegfs played roles induction peri intra tumoral vascularization vegf neutralization bevacizumab effectively reduced tumor growth mainly suppression angiogenesis however increases expression hypoxia inducible factor 1 hif1 hif1 responsive genes vegf vegfr1 vegfr2 carbonic anhydrase ca ix caxii indicated potential subsequent therapeutic resistance supplementation carbonic anhydrase inhibitor acetazolamide enhanced anti cca effects bevacizumab anti angiogenesis anti proliferation observed combination treatment results suggested novel treatment strategy overcome anti angiogenesis resistance importance induced essentiality treatment cca stn","probabilities":0.9467213,"Title":"Inhibition Of Carbonic Anhydrase Potentiates Bevacizumab Treatment In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a unique liver cancer subtype with an increasing incidence globally. The lack of specific symptoms and definite diagnostic markers results in a delayed diagnosis and disease progression. Systemic chemotherapy is commonly selected for advanced CCA even though its advantages remain unknown. Targeted therapy, especially anti-vascular endothelial growth factor (VEGF) therapy, is promising for CCA; however, improvements in the therapeutic regimen are necessary to overcome subsequent resistance. We demonstrated VEGF expression was higher in CCA cell lines than in other liver cancer cells. Secreted VEGFs played roles in the induction of peri- and intra-tumoral vascularization. VEGF neutralization by bevacizumab effectively reduced tumor growth, mainly through the suppression of angiogenesis; however, increases in the expression of hypoxia-inducible factor 1α (HIF1α) and HIF1α-responsive genes (such as VEGF, VEGFR1, VEGFR2, carbonic anhydrase (CA) IX and CAXII) indicated the potential for subsequent therapeutic resistance. Supplementation with a carbonic anhydrase inhibitor, acetazolamide, enhanced the anti-CCA effects of bevacizumab. Anti-angiogenesis and anti-proliferation were observed with the combination treatment. These results suggested a novel treatment strategy to overcome anti-angiogenesis resistance and the importance of \"induced essentiality\" in the treatment of CCA.","Source":"STN","category":"ANIMAL","training_data":"Inhibition Of Carbonic Anhydrase Potentiates Bevacizumab Treatment In Cholangiocarcinoma Cholangiocarcinoma (CCA) is a unique liver cancer subtype with an increasing incidence globally. The lack of specific symptoms and definite diagnostic markers results in a delayed diagnosis and disease progression. Systemic chemotherapy is commonly selected for advanced CCA even though its advantages remain unknown. Targeted therapy, especially anti-vascular endothelial growth factor (VEGF) therapy, is promising for CCA; however, improvements in the therapeutic regimen are necessary to overcome subsequent resistance. We demonstrated VEGF expression was higher in CCA cell lines than in other liver cancer cells. Secreted VEGFs played roles in the induction of peri- and intra-tumoral vascularization. VEGF neutralization by bevacizumab effectively reduced tumor growth, mainly through the suppression of angiogenesis; however, increases in the expression of hypoxia-inducible factor 1α (HIF1α) and HIF1α-responsive genes (such as VEGF, VEGFR1, VEGFR2, carbonic anhydrase (CA) IX and CAXII) indicated the potential for subsequent therapeutic resistance. Supplementation with a carbonic anhydrase inhibitor, acetazolamide, enhanced the anti-CCA effects of bevacizumab. Anti-angiogenesis and anti-proliferation were observed with the combination treatment. These results suggested a novel treatment strategy to overcome anti-angiogenesis resistance and the importance of \"induced essentiality\" in the treatment of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"outcomes patients 80 years diagnosis hepatopancreaticobiliary hpb malignancy older patients underrepresented oncological clinical trials incidence hepatopancreaticobiliary hpb malignancies higher older patients data outcomes lacking study assessed patient outcomes 80 80 years hpb malignancy seen tertiary referral centre christie nhs foundation trust data patients hpb malignancy collected retrospectively 2012 2017 via line case note review survival calculated using kaplan meier method prognostic factors using log rank analysis 1421 patients 10 80 years patients 80 80 years 56 57 pancreas cancer 39 36 biliary tract cancer 5 7 hepatocellular carcinoma respectively amongst patients 80 years 75 eastern cooperative oncology group performance status ecog ps 0 2 patients 80 years higher rates comorbidity 28 received systemic anti cancer therapy sact compared 62 patients 80 years best supportive care bsc instituted 44 older patients compared 13 80 years patients 80 years received sact 82 received monotherapy median overall survival os patients receiving palliative sact 10 07 months 95 ci 8 89 11 08 10 10 months 95 ci 6 30 12 30 patients 80 80 years respectively p 0 41 ecog ps p 0 001 prognostic os older patients adult comorbidity evaluation 27 comorbidity score p 0 07 comparing groups ace score 1 1 baseline factors similar age cohorts comorbidities present older patients older patients less likely receive sact equivalent benefit os younger patients pubmed","probabilities":0.9799733,"Title":"Outcomes in patients ≥ 80 years with a diagnosis of a hepatopancreaticobiliary (HPB) malignancy","Abstract":"Older patients are underrepresented in oncological clinical trials. The incidence of hepatopancreaticobiliary (HPB) malignancies is higher in older patients, but data on outcomes are lacking. This study assessed patient outcomes in those < 80 and ≥ 80 years with a HPB malignancy seen at a tertiary referral centre, The Christie NHS Foundation Trust. Data on patients with a HPB malignancy were collected retrospectively between 2012 and 2017 via on-line case-note review. Survival was calculated using the Kaplan-Meier method and prognostic factors using log-rank analysis. Of 1421 patients, 10% were ≥ 80 years. Of patients < 80 and ≥ 80 years, 56% and 57% had pancreas cancer, 39% and 36% biliary tract cancer, and 5% and 7% had hepatocellular carcinoma, respectively. Amongst patients ≥ 80 years, 75% had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. Patients ≥ 80 years had higher rates of comorbidity; 28% received systemic anti-cancer therapy (SACT), compared with 62% of patients < 80 years. Best supportive care (BSC) was instituted in 44% of older patients, compared with 13% in those < 80 years. Of patients ≥ 80 years who received SACT, 82% received monotherapy. Median overall survival (OS) for patients receiving palliative SACT was 10.07 months (95% CI 8.89-11.08) and 10.10 months (95% CI 6.30-12.30) in patients < 80 and ≥ 80 years, respectively, p 0.41; ECOG PS (p < 0.001) was prognostic for OS in older patients but Adult Comorbidity Evaluation-27 comorbidity score (p = 0.07, when comparing groups of ACE score ≤ 1 and > 1) was not. Baseline factors were similar in both age cohorts, but more comorbidities were present in older patients. Older patients were less likely to receive SACT, but when they did, they had an equivalent benefit in OS to younger patients.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes in patients ≥ 80 years with a diagnosis of a hepatopancreaticobiliary (HPB) malignancy Older patients are underrepresented in oncological clinical trials. The incidence of hepatopancreaticobiliary (HPB) malignancies is higher in older patients, but data on outcomes are lacking. This study assessed patient outcomes in those < 80 and ≥ 80 years with a HPB malignancy seen at a tertiary referral centre, The Christie NHS Foundation Trust. Data on patients with a HPB malignancy were collected retrospectively between 2012 and 2017 via on-line case-note review. Survival was calculated using the Kaplan-Meier method and prognostic factors using log-rank analysis. Of 1421 patients, 10% were ≥ 80 years. Of patients < 80 and ≥ 80 years, 56% and 57% had pancreas cancer, 39% and 36% biliary tract cancer, and 5% and 7% had hepatocellular carcinoma, respectively. Amongst patients ≥ 80 years, 75% had an Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2. Patients ≥ 80 years had higher rates of comorbidity; 28% received systemic anti-cancer therapy (SACT), compared with 62% of patients < 80 years. Best supportive care (BSC) was instituted in 44% of older patients, compared with 13% in those < 80 years. Of patients ≥ 80 years who received SACT, 82% received monotherapy. Median overall survival (OS) for patients receiving palliative SACT was 10.07 months (95% CI 8.89-11.08) and 10.10 months (95% CI 6.30-12.30) in patients < 80 and ≥ 80 years, respectively, p 0.41; ECOG PS (p < 0.001) was prognostic for OS in older patients but Adult Comorbidity Evaluation-27 comorbidity score (p = 0.07, when comparing groups of ACE score ≤ 1 and > 1) was not. Baseline factors were similar in both age cohorts, but more comorbidities were present in older patients. Older patients were less likely to receive SACT, but when they did, they had an equivalent benefit in OS to younger patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"concomitant hepatic artery resection advanced perihilar cholangiocarcinoma case control study propensity score matching background whether concomitant hepatic artery resection har improves prognosis advanced perihilar cholangiocarcinoma remains controversial aim present study compare short long term surgical results har versus standard resection sr perihilar cholangiocarcinoma using propensity score matching methods among 209 patients perihilar cholangiocarcinoma patients underwent resection department 28 patients underwent har remaining 181 patients underwent sr adjust differences clinicopathological factors including difficulty surgery groups propensity score matching used 1 1 ratio resulting comparison 24 patients per group study protocols approved institutional review board 015 0365 enrolled umin ctr umin000019927 conducted according declaration helsinki results significant differences seen overall incidence postoperative complications clavien dindo classification iiia 37 5 sr group vs 62 5 har group p 0 080 except postoperative liver abscess formation p 0 020 five year overall survival rates 30 3 20 4 respectively significant difference overall survival rate apparent sr har groups p 0 150 conclusion despite demanding procedure concomitant har appears feasible selected patients perihilar cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Concomitant hepatic artery resection for advanced perihilar cholangiocarcinoma: a case-control study with propensity score matching","Abstract":"BACKGROUND: Whether concomitant hepatic artery resection (HAR) improves the prognosis for advanced perihilar cholangiocarcinoma remains controversial. The aim of the present study was to compare short- and long-term surgical results of HAR versus standard resection (SR) for perihilar cholangiocarcinoma using propensity score matching. METHODS: Among 209 patients with perihilar cholangiocarcinoma patients who underwent resection in our department, 28 patients underwent HAR, and the remaining 181 patients underwent SR. To adjust for differences in clinicopathological factors, including difficulty in surgery, between groups, propensity score matching was used at a 1:1 ratio, resulting in a comparison of 24 patients per group. The study protocols were approved by our institutional review board (015-0365), enrolled in UMIN-CTR (No: UMIN000019927), and conducted according to the Declaration of Helsinki. RESULTS: No significant differences were seen in overall incidence of postoperative complications (Clavien-Dindo classification ≥IIIa: 37.5% in SR group vs. 62.5% in HAR group; P = 0.080), except for postoperative liver abscess formation (P = 0.020). Five-year overall survival rates were 30.3% and 20.4%, respectively. No significant difference in overall survival rate was apparent between the SR and HAR groups (P = 0.150). CONCLUSION: Despite being a demanding procedure, concomitant HAR appears feasible for selected patients with perihilar cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Concomitant hepatic artery resection for advanced perihilar cholangiocarcinoma: a case-control study with propensity score matching BACKGROUND: Whether concomitant hepatic artery resection (HAR) improves the prognosis for advanced perihilar cholangiocarcinoma remains controversial. The aim of the present study was to compare short- and long-term surgical results of HAR versus standard resection (SR) for perihilar cholangiocarcinoma using propensity score matching. METHODS: Among 209 patients with perihilar cholangiocarcinoma patients who underwent resection in our department, 28 patients underwent HAR, and the remaining 181 patients underwent SR. To adjust for differences in clinicopathological factors, including difficulty in surgery, between groups, propensity score matching was used at a 1:1 ratio, resulting in a comparison of 24 patients per group. The study protocols were approved by our institutional review board (015-0365), enrolled in UMIN-CTR (No: UMIN000019927), and conducted according to the Declaration of Helsinki. RESULTS: No significant differences were seen in overall incidence of postoperative complications (Clavien-Dindo classification ≥IIIa: 37.5% in SR group vs. 62.5% in HAR group; P = 0.080), except for postoperative liver abscess formation (P = 0.020). Five-year overall survival rates were 30.3% and 20.4%, respectively. No significant difference in overall survival rate was apparent between the SR and HAR groups (P = 0.150). CONCLUSION: Despite being a demanding procedure, concomitant HAR appears feasible for selected patients with perihilar cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"genomic profiling metabolic homeostasis primary liver cancers hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icca two common primary liver cancers represent second common cancer related cause death worldwide cases diagnosed advanced stage recent genome wide studies helped elucidate molecular pathogenesis genetic heterogeneity liver cancers review genetic landscape hcc icca discusses recent findings genomic profiling current understanding pathways involved initiation progression liver cancer highlight recent insights gained metabolic profiling hcc icca knowledge key developing clinically useful diagnostic prognostic profiles building targeted molecular immunologic therapies ultimately curing complex heterogeneous diseases pubmed","probabilities":0.9799733,"Title":"Genomic Profiling and Metabolic Homeostasis in Primary Liver Cancers","Abstract":"Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), the two most common primary liver cancers, represent the second most common cancer-related cause of death worldwide, with most cases being diagnosed at an advanced stage. Recent genome-wide studies have helped to elucidate the molecular pathogenesis and genetic heterogeneity of liver cancers. This review of the genetic landscape of HCC and iCCA discusses the most recent findings from genomic profiling and the current understanding of the pathways involved in the initiation and progression of liver cancer. We highlight recent insights gained from metabolic profiling of HCC and iCCA. This knowledge will be key to developing clinically useful diagnostic/prognostic profiles, building targeted molecular and immunologic therapies, and ultimately curing these complex and heterogeneous diseases.","Source":"PubMed","category":"HUMAN","training_data":"Genomic Profiling and Metabolic Homeostasis in Primary Liver Cancers Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), the two most common primary liver cancers, represent the second most common cancer-related cause of death worldwide, with most cases being diagnosed at an advanced stage. Recent genome-wide studies have helped to elucidate the molecular pathogenesis and genetic heterogeneity of liver cancers. This review of the genetic landscape of HCC and iCCA discusses the most recent findings from genomic profiling and the current understanding of the pathways involved in the initiation and progression of liver cancer. We highlight recent insights gained from metabolic profiling of HCC and iCCA. This knowledge will be key to developing clinically useful diagnostic/prognostic profiles, building targeted molecular and immunologic therapies, and ultimately curing these complex and heterogeneous diseases. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact skeletal muscle mass survival outcome biliary tract cancer patients low skeletal muscle mass frequently observed cancer patients known poor prognostic factor survival outcomes purposes study determine prevalence sarcopenia relation mortality biliary tract cancer body composition measurements skeletal muscle index total fat mass bone mineral content evaluated using dual energy x ray absorptiometry 75 biliary tract cancer patients chemotherapy muscle strength measured handgrip strength gait speed overall survival associated factors determined mean appendicular muscle mass 17 8 2 7 kg men 14 0 2 1 kg women p 0 05 sarcopenia diagnosed 46 patients 61 3 higher proportion men classified sarcopenia women 69 0 vs 35 3 p 0 05 multivariable analysis adjusted chemotherapy regimen age revealed high appendicular muscle mass independently predicted better survival outcomes hr 0 40 95 ci 0 18 0 88 p 0 023 sarcopenia common biliary tract cancer patients low appendicular muscle mass associated poor survival outcome pubmed","probabilities":0.9799733,"Title":"The impact of skeletal muscle mass on survival outcome in biliary tract cancer patients","Abstract":"Low skeletal muscle mass is frequently observed in cancer patients and is known to be a poor prognostic factor for survival outcomes. The purposes of our study were to determine the prevalence of sarcopenia and its relation to mortality in biliary tract cancer. Body composition measurements (skeletal muscle index, total fat mass, bone mineral content) were evaluated by using dual-energy x-ray absorptiometry in 75 biliary tract cancer patients before chemotherapy. Muscle strength was measured by handgrip strength and gait speed. Overall survival and its associated factors were determined. The mean appendicular muscle mass was 17.8±2.7 kg in men and 14.0±2.1 kg in women (p < 0.05). Sarcopenia was diagnosed in 46 patients (61.3%) and higher proportion of men was classified as sarcopenia than women (69.0% vs 35.3%, p < 0.05). Multivariable analysis adjusted for chemotherapy regimen and age revealed that high appendicular muscle mass independently predicted better survival outcomes (HR 0.40; 95% CI, 0.18 to 0.88; p = 0.023). Sarcopenia is common in biliary tract cancer patients and low appendicular muscle mass was associated with poor survival outcome.","Source":"PubMed","category":"HUMAN","training_data":"The impact of skeletal muscle mass on survival outcome in biliary tract cancer patients Low skeletal muscle mass is frequently observed in cancer patients and is known to be a poor prognostic factor for survival outcomes. The purposes of our study were to determine the prevalence of sarcopenia and its relation to mortality in biliary tract cancer. Body composition measurements (skeletal muscle index, total fat mass, bone mineral content) were evaluated by using dual-energy x-ray absorptiometry in 75 biliary tract cancer patients before chemotherapy. Muscle strength was measured by handgrip strength and gait speed. Overall survival and its associated factors were determined. The mean appendicular muscle mass was 17.8±2.7 kg in men and 14.0±2.1 kg in women (p < 0.05). Sarcopenia was diagnosed in 46 patients (61.3%) and higher proportion of men was classified as sarcopenia than women (69.0% vs 35.3%, p < 0.05). Multivariable analysis adjusted for chemotherapy regimen and age revealed that high appendicular muscle mass independently predicted better survival outcomes (HR 0.40; 95% CI, 0.18 to 0.88; p = 0.023). Sarcopenia is common in biliary tract cancer patients and low appendicular muscle mass was associated with poor survival outcome. PubMed","prediction_labels":"HUMAN"},{"cleaned":"classify ampullary tumours better clinical pathological molecular features results ageo study background ampullary adenocarcinoma aa originates either intestinal int pancreaticobiliary pb epithelium different prognostic factors recurrence identified previous studies methods 91 aa patients ageo retrospective multicentre cohort evaluated centrally reviewed morphological classification panel markers ang et al including ck7 ck20 muc1 muc2 cdx2 50 gene panel mutational analysis clinicopathological ageo prognostic score results forty three 47 91 tumours ang int 29 32 ang pb 18 20 ambiguous ang amb one classified among 90 tumours 68 7 int tumours ang int 78 2 pb tumours ang pb muc5ac expression detected 32 5 86 evaluable cases among 71 tumours kras tp53 apc pik3ca frequently mutated genes kras mutation significantly frequent pb subtype multivariate analysis ageo prognostic score tumour subtype associated relapse free survival ageo prognostic score associated overall survival conclusions mutational analysis muc5ac expression provide additional value prognostic evaluation aa patients ang et al classification ageo prognostic score confirmed strong prognosticator disease recurrence pubmed","probabilities":0.9799733,"Title":"Can we classify ampullary tumours better? Clinical, pathological and molecular features Results of an AGEO study","Abstract":"BACKGROUND: Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies. METHODS: In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al. including CK7, CK20, MUC1, MUC2 and CDX2, the 50-gene panel mutational analysis, and the clinicopathological AGEO prognostic score. RESULTS: Forty-three (47%) of the 91 tumours were Ang-INT, 29 (32%) were Ang-PB, 18 (20%) were ambiguous (Ang-AMB) and one could not be classified. Among these 90 tumours, 68.7% of INT tumours were Ang-INT and 78.2% of PB tumours were Ang-PB. MUC5AC expression was detected in 32.5% of the 86 evaluable cases. Among 71 tumours, KRAS, TP53, APC and PIK3CA were the most frequently mutated genes. The KRAS mutation was significantly more frequent in the PB subtype. In multivariate analysis, only AGEO prognostic score and tumour subtype were associated with relapse-free survival. Only AGEO prognostic score was associated with overall survival. CONCLUSIONS: Mutational analysis and MUC5AC expression provide no additional value in the prognostic evaluation of AA patients. Ang et al. classification and the AGEO prognostic score were confirmed as a strong prognosticator for disease recurrence.","Source":"PubMed","category":"HUMAN","training_data":"Can we classify ampullary tumours better? Clinical, pathological and molecular features Results of an AGEO study BACKGROUND: Ampullary adenocarcinoma (AA) originates from either intestinal (INT) or pancreaticobiliary (PB) epithelium. Different prognostic factors of recurrence have been identified in previous studies. METHODS: In 91 AA patients of the AGEO retrospective multicentre cohort, we evaluated the centrally reviewed morphological classification, panel markers of Ang et al. including CK7, CK20, MUC1, MUC2 and CDX2, the 50-gene panel mutational analysis, and the clinicopathological AGEO prognostic score. RESULTS: Forty-three (47%) of the 91 tumours were Ang-INT, 29 (32%) were Ang-PB, 18 (20%) were ambiguous (Ang-AMB) and one could not be classified. Among these 90 tumours, 68.7% of INT tumours were Ang-INT and 78.2% of PB tumours were Ang-PB. MUC5AC expression was detected in 32.5% of the 86 evaluable cases. Among 71 tumours, KRAS, TP53, APC and PIK3CA were the most frequently mutated genes. The KRAS mutation was significantly more frequent in the PB subtype. In multivariate analysis, only AGEO prognostic score and tumour subtype were associated with relapse-free survival. Only AGEO prognostic score was associated with overall survival. CONCLUSIONS: Mutational analysis and MUC5AC expression provide no additional value in the prognostic evaluation of AA patients. Ang et al. classification and the AGEO prognostic score were confirmed as a strong prognosticator for disease recurrence. PubMed","prediction_labels":"HUMAN"},{"cleaned":"state art management locally advanced metastatic gallbladder cancer purpose review gallbladder carcinoma gbc classified biliary tract cancer btc along intrahepatic extrahepatic cholangiocarcinomas rare disease western countries highly prevalent disease chile countries latin america india japan commonly presents advanced stage limited therapeutic options cisplatin gemcitabine emerged first line standard care patients advanced btcs prognosis remains poor development molecularly targeted therapies advanced btc remains challenging recent findings comprehension molecular events gallbladder carcinogenesis may provide novel targeted therapeutic approach early stage clinical trials targeted therapies appear promising although relationship subsets patients positive responses therapy tumor genetics requires exploration recent developments targeted therapeutics directed several key signalling pathways btc including epidermal growth factor receptor angiogenesis mitogen activated protein kinase pathway discussed addition potential application prognostic factors markers summary future therapeutic spectrum btc gbc likely encompass novel combinations targeted therapies cytostatics scientifically molecularly directed schedules thus permitting fewer mechanisms escape tumor cells pubmed","probabilities":0.9799733,"Title":"State-of-the-art in the management of locally advanced and metastatic gallbladder cancer","Abstract":"PURPOSE OF REVIEW: Gallbladder carcinoma (GBC), classified as a biliary tract cancer (BTC) along with intrahepatic and extrahepatic cholangiocarcinomas, is a rare disease in Western countries, but a highly prevalent disease in Chile, other countries in Latin America, India and Japan. It commonly presents at an advanced stage, and has limited therapeutic options. Cisplatin/gemcitabine has emerged as the first-line standard of care for patients with advanced BTCs, but the prognosis remains poor. Development of molecularly targeted therapies in advanced BTC remains challenging. RECENT FINDINGS: Comprehension of the molecular events in gallbladder carcinogenesis may provide a novel targeted therapeutic approach, and early stage clinical trials with targeted therapies appear promising, although the relationship between subsets of patients with positive responses to therapy and tumor genetics requires further exploration. Recent developments in targeted therapeutics, directed against several key signalling pathways in BTC, including epidermal growth factor receptor, angiogenesis, and the mitogen-activated protein kinase pathway will be discussed, in addition to the potential application of prognostic factors and markers. SUMMARY: The future therapeutic spectrum for BTC and GBC will likely encompass novel combinations of targeted therapies with cytostatics in scientifically and molecularly directed schedules, thus permitting fewer mechanisms of escape for tumor cells.","Source":"PubMed","category":"HUMAN","training_data":"State-of-the-art in the management of locally advanced and metastatic gallbladder cancer PURPOSE OF REVIEW: Gallbladder carcinoma (GBC), classified as a biliary tract cancer (BTC) along with intrahepatic and extrahepatic cholangiocarcinomas, is a rare disease in Western countries, but a highly prevalent disease in Chile, other countries in Latin America, India and Japan. It commonly presents at an advanced stage, and has limited therapeutic options. Cisplatin/gemcitabine has emerged as the first-line standard of care for patients with advanced BTCs, but the prognosis remains poor. Development of molecularly targeted therapies in advanced BTC remains challenging. RECENT FINDINGS: Comprehension of the molecular events in gallbladder carcinogenesis may provide a novel targeted therapeutic approach, and early stage clinical trials with targeted therapies appear promising, although the relationship between subsets of patients with positive responses to therapy and tumor genetics requires further exploration. Recent developments in targeted therapeutics, directed against several key signalling pathways in BTC, including epidermal growth factor receptor, angiogenesis, and the mitogen-activated protein kinase pathway will be discussed, in addition to the potential application of prognostic factors and markers. SUMMARY: The future therapeutic spectrum for BTC and GBC will likely encompass novel combinations of targeted therapies with cytostatics in scientifically and molecularly directed schedules, thus permitting fewer mechanisms of escape for tumor cells. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinocopathological study depth pf subserosal invasion patients gallbladder carcinoma background examined whether depth subserosal cancer invasion predicts lymph node involvement survival gallbladder carcinoma gbc patients pathologicial subserosal invasion pt2 explore patients benefit radical second resection among patients inapparent pt2 tumor methods subjects comprised 31 patients pt2 gbc thickness subserosal layer vertical length carcinoma invasion subserosa measured microscopy depth subserosal invasion divided subjectively three categories ss1 ss2 ss3 invasion upper middle lower thirds subserosal layer respectively relationships subserosal subclassification histopathological factors prognosis examined results subserosal layers significantly thicker p 0 001 portions cancer invasion 5 46 0 68 mm range 1 0 13 75 mm without cancer invasion 1 89 0 16 mm range 0 88 4 50 mm depth carcinoma invasion subserosa 4 20 0 65 mm range 0 25 12 5 mm rate lymphatic permeation venous permeation lymph node involvement significantly increased deeper subserosal invasion p 0 014 p 0 027 p 0 018 respectively among histopathological factors examined subserosal subclassification significant correlation presence absence lymph node metastasis significant correlation p 0 043 degree subserosal invasion ss1 ss2 ss3 involved nodal disease pn0 pn1 pm1 lymph although 5 year survival rates according degree subserosal invasion tended decrease deeper invasion subserosal layer ss1 83 3 ss2 62 5 ss3 50 0 significant differences noted conclusions pathological characteristics tend become aggressive increasing depth subserous carcinoma invasion pt2 gbc depth subserosal invasion predictor presence degree lymph node metastasis pt2 gbc sampling biopsy para aortic nodes recommended inapparent pt2 gbc patients subserosal invasion beyond one thirds subserosal layer undergo radical second resection google scholar","probabilities":0.9799733,"Title":"Clinocopathological Study Of Depth Pf Subserosal Invasion In Patients With Gallbladder Carcinoma","Abstract":"Background\nWe examined whether depth of subserosal cancer invasion predicts lymph node involvement and survival in gallbladder carcinoma (GBC) patients with pathologicial subserosal invasion (pT2), to explore which patients benefit from radical second resection among patients with inapparent pT2 tumor.\nMethods\nSubjects comprised 31 patients with pT2 GBC. Thickness of the subserosal layer and vertical length of carcinoma invasion into the subserosa were measured under microscopy. Depth of subserosal invasion was divided subjectively into three categories: ss1, ss2, and ss3 (invasion of upper, middle, and lower thirds of the subserosal layer, respectively). Relationships between subserosal subclassification, histopathological factors, and prognosis were examined.\nResults\nSubserosal layers were significantly thicker (P  < 0.001) in portions with cancer invasion (5.46 ± 0.68 mm; range 1.0 ∼ 13.75 mm) than those without cancer invasion (1.89 ± 0.16 mm, range, 0.88 ∼ 4.50 mm). Depth of carcinoma invasion into subserosa was 4.20 ± 0.65 mm (range, 0.25 ∼ 12.5 mm). Rate of lymphatic permeation, venous permeation, and lymph node involvement significantly increased with deeper subserosal invasion (P  = 0.014, P  = 0.027, P  = 0.018, respectively). Among histopathological factors examined, only subserosal subclassification had a significant correlation with presence or absence of lymph node metastasis. Further, there was a significant correlation (P  = 0.043) between the degree of subserosal invasion (ss1, ss2, and ss3) and involved nodal disease (pN0, pN1, and pM1 [lymph]). Although 5‐year survival rates, according to the degree of subserosal invasion, tended to decrease with deeper invasion into the subserosal layer (ss1, 83.3%; ss2, 62.5%; ss3, 50.0%), no significant differences were noted. \nConclusions\nPathological characteristics tend to become more aggressive with increasing depth of subserous carcinoma invasion in pT2 GBC. Depth of subserosal invasion is a predictor of presence and degree of lymph node metastasis in pT2 GBC. A sampling biopsy of the para‐aortic nodes is recommended for inapparent pT2 GBC patients with subserosal invasion beyond one‐thirds of the subserosal layer when they undergo radical second resection.","Source":"Google Scholar","category":"HUMAN","training_data":"Clinocopathological Study Of Depth Pf Subserosal Invasion In Patients With Gallbladder Carcinoma Background\nWe examined whether depth of subserosal cancer invasion predicts lymph node involvement and survival in gallbladder carcinoma (GBC) patients with pathologicial subserosal invasion (pT2), to explore which patients benefit from radical second resection among patients with inapparent pT2 tumor.\nMethods\nSubjects comprised 31 patients with pT2 GBC. Thickness of the subserosal layer and vertical length of carcinoma invasion into the subserosa were measured under microscopy. Depth of subserosal invasion was divided subjectively into three categories: ss1, ss2, and ss3 (invasion of upper, middle, and lower thirds of the subserosal layer, respectively). Relationships between subserosal subclassification, histopathological factors, and prognosis were examined.\nResults\nSubserosal layers were significantly thicker (P  < 0.001) in portions with cancer invasion (5.46 ± 0.68 mm; range 1.0 ∼ 13.75 mm) than those without cancer invasion (1.89 ± 0.16 mm, range, 0.88 ∼ 4.50 mm). Depth of carcinoma invasion into subserosa was 4.20 ± 0.65 mm (range, 0.25 ∼ 12.5 mm). Rate of lymphatic permeation, venous permeation, and lymph node involvement significantly increased with deeper subserosal invasion (P  = 0.014, P  = 0.027, P  = 0.018, respectively). Among histopathological factors examined, only subserosal subclassification had a significant correlation with presence or absence of lymph node metastasis. Further, there was a significant correlation (P  = 0.043) between the degree of subserosal invasion (ss1, ss2, and ss3) and involved nodal disease (pN0, pN1, and pM1 [lymph]). Although 5‐year survival rates, according to the degree of subserosal invasion, tended to decrease with deeper invasion into the subserosal layer (ss1, 83.3%; ss2, 62.5%; ss3, 50.0%), no significant differences were noted. \nConclusions\nPathological characteristics tend to become more aggressive with increasing depth of subserous carcinoma invasion in pT2 GBC. Depth of subserosal invasion is a predictor of presence and degree of lymph node metastasis in pT2 GBC. A sampling biopsy of the para‐aortic nodes is recommended for inapparent pT2 GBC patients with subserosal invasion beyond one‐thirds of the subserosal layer when they undergo radical second resection. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"circulating mir 192 liver fluke associated cholangiocarcinoma patients prospective prognostic indicator background study aimed investigate mir 192 levels patients sera liver fluke associated cholangiocarcinoma cca prospective prognostic indicator methods microrna polymerase chain reaction pcr array performed using pooled serum samples 11 cca patients nine healthy subjects selected mirnas verified differential levels sera tumor tissues patients opisthorchis viverrini ov induced cca model using taqman mirna expression assay results results demonstrated mir 192 significantly higher serum cca patients healthy subjects giving sensitivity 74 specificity 72 area curve auc 0 803 95 confidence interval ci 0 708 0 897 p 0 0001 serum mir 192 examined ov infected subjects subjects periductal fibrosis increased statistically significantly compared healthy subjects high levels serum mir 192 significantly correlated lymph node metastasis p 0 047 shorter survival compared individuals low levels serum mir 192 hazard ratio hr 2 076 95 ci 1 004 4 291 p 0 049 also found expression levels mir 192 appeared elevated cca tissues patients ov induced cca tissues hamster model conclusions finding indicates elevated levels mir 192 may involved cca genesis potential utility noninvasive prognostic indicator cca patients pubmed","probabilities":0.9285714,"Title":"Circulating miR-192 in liver fluke-associated cholangiocarcinoma patients: a prospective prognostic indicator","Abstract":"BACKGROUND: This study aimed to investigate the miR-192 levels in patients' sera of liver fluke-associated cholangiocarcinoma (CCA) for a prospective prognostic indicator. METHODS: MicroRNA polymerase chain reaction (PCR) array was performed using pooled serum samples from 11 CCA patients and nine healthy subjects. Selected miRNAs were verified for the differential levels in both sera and tumor tissues (of patients and Opisthorchis viverrini (Ov)-induced CCA model) using TaqMan miRNA expression assay. RESULTS: Our results demonstrated that miR-192 was significantly higher in the serum of CCA patients than that in healthy subjects giving a sensitivity of 74% and specificity of 72% (area under the curve [AUC] = 0.803; 95% confidence interval [CI], 0.708-0.897, P < 0.0001). Serum miR-192 examined in Ov infected subjects and subjects with periductal fibrosis were increased but not statistically significantly when compared with healthy subjects. High levels of serum miR-192 were significantly correlated with lymph node metastasis (P = 0.047) and shorter survival compared with individuals with low levels of serum miR-192 (hazard ratio [HR] 2.076, 95% CI 1.004-4.291, P = 0.049). We also found that the expression levels of miR-192 appeared to be elevated in both CCA tissues of patients and in Ov-induced CCA tissues of a hamster model. CONCLUSIONS: This finding indicates that elevated levels of miR-192 may be involved in CCA genesis and have a potential utility as a noninvasive prognostic indicator for CCA patients.","Source":"PubMed","category":"ANIMAL","training_data":"Circulating miR-192 in liver fluke-associated cholangiocarcinoma patients: a prospective prognostic indicator BACKGROUND: This study aimed to investigate the miR-192 levels in patients' sera of liver fluke-associated cholangiocarcinoma (CCA) for a prospective prognostic indicator. METHODS: MicroRNA polymerase chain reaction (PCR) array was performed using pooled serum samples from 11 CCA patients and nine healthy subjects. Selected miRNAs were verified for the differential levels in both sera and tumor tissues (of patients and Opisthorchis viverrini (Ov)-induced CCA model) using TaqMan miRNA expression assay. RESULTS: Our results demonstrated that miR-192 was significantly higher in the serum of CCA patients than that in healthy subjects giving a sensitivity of 74% and specificity of 72% (area under the curve [AUC] = 0.803; 95% confidence interval [CI], 0.708-0.897, P < 0.0001). Serum miR-192 examined in Ov infected subjects and subjects with periductal fibrosis were increased but not statistically significantly when compared with healthy subjects. High levels of serum miR-192 were significantly correlated with lymph node metastasis (P = 0.047) and shorter survival compared with individuals with low levels of serum miR-192 (hazard ratio [HR] 2.076, 95% CI 1.004-4.291, P = 0.049). We also found that the expression levels of miR-192 appeared to be elevated in both CCA tissues of patients and in Ov-induced CCA tissues of a hamster model. CONCLUSIONS: This finding indicates that elevated levels of miR-192 may be involved in CCA genesis and have a potential utility as a noninvasive prognostic indicator for CCA patients. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"targeting il 6 dependent phenotype identify novel therapies cholangiocarcinoma background need new therapies cholangiocarcinoma highlighted poor prognosis refractoriness chemotherapy increased production interleukin 6 promotes cholangiocarcinoma growth contributes chemoresistance activating cell survival mechanisms sought identify biologically active compounds capable ameliorating phenotypic effects il 6 expression explore potential therapeutic use cholangiocarcinoma methodology genomic signature associated interleukin 6 expression mz cha 1 human malignant cholangiocytes derived computational bioinformatics analysis performed identify compounds induced inverse gene changes signature effect compounds cholangiocarcinoma growth experimentally verified vitro vivo interactions therapeutic agents evaluated using median effects analysis principal findings group structurally related compounds nitrendipine nifedipine felodipine identified three compounds cytotoxic mz cha 1 cells ic50 felodipine 26 m nitrendipine 44 m nifedipine 15 m similar results observed kmch 1 cc lp 1 tfk 1 cholangiocarcinoma cell lines fractional effect 0 5 three agents synergistic either camptothecin gemcitabine mz cha 1 cells vitro co administration felodipine gemcitabine decreased growth mz cha 1 cell xenografts nude athymic mice conclusions computational bioinformatics analysis phenotype based genomic expression used identify therapeutic agents using drug discovery approach based targeting defined tumor associated phenotype identified compounds potential therapeutic use cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Targeting The Il-6 Dependent Phenotype Can Identify Novel Therapies For Cholangiocarcinoma","Abstract":"Background: The need for new therapies for cholangiocarcinoma is highlighted by their poor prognosis and refractoriness to chemotherapy. Increased production of Interleukin-6 promotes cholangiocarcinoma growth and contributes to chemoresistance by activating cell survival mechanisms. We sought to identify biologically active compounds capable of ameliorating the phenotypic effects of IL-6 expression and to explore their potential therapeutic use for cholangiocarcinoma. \r\n\r\n Methodology: A genomic signature associated with Interleukin-6 expression in Mz-ChA-1 human malignant cholangiocytes was derived. Computational bioinformatics analysis was performed to identify compounds that induced inverse gene changes to the signature. The effect of these compounds on cholangiocarcinoma growth was then experimentally verified in vitro and in vivo. Interactions with other therapeutic agents were evaluated using median effects analysis. \r\n\r\n Principal findings: A group of structurally related compounds, nitrendipine, nifedipine and felodipine was identified. All three compounds were cytotoxic to Mz-ChA-1 cells with an IC50 for felodipine of 26 µM, nitrendipine, 44 µM and nifedipine, 15 µM. Similar results were observed in KMCH-1, CC-LP-1 and TFK-1 cholangiocarcinoma cell lines. At a fractional effect of 0.5, all three agents were synergistic with either camptothecin or gemcitabine in Mz-ChA-1 cells in vitro. Co-administration of felodipine and gemcitabine decreased the growth of Mz-ChA-1 cell xenografts in nude athymic mice. \r\n\r\n Conclusions: Computational bioinformatics analysis of phenotype-based genomic expression can be used to identify therapeutic agents. Using this drug discovery approach based on targeting a defined tumor associated phenotype, we identified compounds with the potential for therapeutic use in cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Targeting The Il-6 Dependent Phenotype Can Identify Novel Therapies For Cholangiocarcinoma Background: The need for new therapies for cholangiocarcinoma is highlighted by their poor prognosis and refractoriness to chemotherapy. Increased production of Interleukin-6 promotes cholangiocarcinoma growth and contributes to chemoresistance by activating cell survival mechanisms. We sought to identify biologically active compounds capable of ameliorating the phenotypic effects of IL-6 expression and to explore their potential therapeutic use for cholangiocarcinoma. \r\n\r\n Methodology: A genomic signature associated with Interleukin-6 expression in Mz-ChA-1 human malignant cholangiocytes was derived. Computational bioinformatics analysis was performed to identify compounds that induced inverse gene changes to the signature. The effect of these compounds on cholangiocarcinoma growth was then experimentally verified in vitro and in vivo. Interactions with other therapeutic agents were evaluated using median effects analysis. \r\n\r\n Principal findings: A group of structurally related compounds, nitrendipine, nifedipine and felodipine was identified. All three compounds were cytotoxic to Mz-ChA-1 cells with an IC50 for felodipine of 26 µM, nitrendipine, 44 µM and nifedipine, 15 µM. Similar results were observed in KMCH-1, CC-LP-1 and TFK-1 cholangiocarcinoma cell lines. At a fractional effect of 0.5, all three agents were synergistic with either camptothecin or gemcitabine in Mz-ChA-1 cells in vitro. Co-administration of felodipine and gemcitabine decreased the growth of Mz-ChA-1 cell xenografts in nude athymic mice. \r\n\r\n Conclusions: Computational bioinformatics analysis of phenotype-based genomic expression can be used to identify therapeutic agents. Using this drug discovery approach based on targeting a defined tumor associated phenotype, we identified compounds with the potential for therapeutic use in cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"coagulopathy associated poor prognosis intrahepatic cholangiocarcinoma patients curative resection rare type liver cancer intrahepatic cholangiocarcinoma icc become increasingly important malignancy continues present significant therapeutic challenges since coagulopathy associated poor prognosis hepatocellular carcinoma hcc prognostic factors icc curative resection still clear aim analyze characteristics icc patients coagulopathy correlation prognosis january 2000 june 2011 541 icc patients curative resection enrolled study survival curves depicted kaplan meier method analyzed log rank test cox proportional hazard regression adopted multivariate survival analysis student test performed analyze difference coagulopathy group normal group correlation coagulation parameters prognosis also evaluated incidence rate least one coagulation parameter abnormality 22 6 122 541 pt common factor 8 87 48 541 one year survival rate patients coagulopathy significantly lower patients normal coagulation p 0 01 univariate analysis patients prolonged pt associated shortened dfs p 0 05 meanwhile pt negatively correlated pre albumin level tnm stage ca19 9 ggt pre albumin level independent prognostic factors dfs multivariate analysis conclusion incidence rate coagulopathy icc patients lower hcc patients prolonged pt advanced tnm stage low pre albumin level high ca19 9 ggt level correlated high recurrence rate poor prognosis pubmed","probabilities":0.9799733,"Title":"Coagulopathy associated with poor prognosis in intrahepatic cholangiocarcinoma patients after curative resection","Abstract":"As a rare type of liver cancer, intrahepatic cholangiocarcinoma (ICC) has become an increasingly important malignancy and continues to present significant therapeutic challenges. Since coagulopathy is associated with poor prognosis in hepatocellular carcinoma (HCC), and prognostic factors of ICC after curative resection were still not clear, we aim to analyze the characteristics of ICC patients with coagulopathy and its correlation to prognosis. From January 2000 to June 2011, 541 ICC patients, after curative resection, were enrolled in our study. Survival curves were depicted by the Kaplan-Meier method and analyzed by the log-rank test. The Cox proportional hazard regression was adopted for multivariate survival analysis. Student's t test was performed to analyze the difference between the coagulopathy group and the normal group. The correlation between coagulation parameters and prognosis was also evaluated. The incidence rate of at least one coagulation parameter abnormality was 22.6% (122/541) while PT was the most common factor (8.87%, 48/541). The one-year survival rate of patients with coagulopathy was significantly lower than that of patients with normal coagulation (p < 0.01). In a univariate analysis, patients with prolonged PT was associated with shortened DFS (p < 0.05). Meanwhile, PT was negatively correlated with pre-albumin level. TNM stage, CA19-9, GGT, and pre-albumin level were independent prognostic factors of DFS in the multivariate analysis. In conclusion, the incidence rate of coagulopathy of ICC patients is lower than HCC patients. Prolonged PT, advanced TNM stage, low pre-albumin level, and high CA19-9 and GGT level were correlated with high recurrence rate and poor prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Coagulopathy associated with poor prognosis in intrahepatic cholangiocarcinoma patients after curative resection As a rare type of liver cancer, intrahepatic cholangiocarcinoma (ICC) has become an increasingly important malignancy and continues to present significant therapeutic challenges. Since coagulopathy is associated with poor prognosis in hepatocellular carcinoma (HCC), and prognostic factors of ICC after curative resection were still not clear, we aim to analyze the characteristics of ICC patients with coagulopathy and its correlation to prognosis. From January 2000 to June 2011, 541 ICC patients, after curative resection, were enrolled in our study. Survival curves were depicted by the Kaplan-Meier method and analyzed by the log-rank test. The Cox proportional hazard regression was adopted for multivariate survival analysis. Student's t test was performed to analyze the difference between the coagulopathy group and the normal group. The correlation between coagulation parameters and prognosis was also evaluated. The incidence rate of at least one coagulation parameter abnormality was 22.6% (122/541) while PT was the most common factor (8.87%, 48/541). The one-year survival rate of patients with coagulopathy was significantly lower than that of patients with normal coagulation (p < 0.01). In a univariate analysis, patients with prolonged PT was associated with shortened DFS (p < 0.05). Meanwhile, PT was negatively correlated with pre-albumin level. TNM stage, CA19-9, GGT, and pre-albumin level were independent prognostic factors of DFS in the multivariate analysis. In conclusion, the incidence rate of coagulopathy of ICC patients is lower than HCC patients. Prolonged PT, advanced TNM stage, low pre-albumin level, and high CA19-9 and GGT level were correlated with high recurrence rate and poor prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"platelet lymphocyte ratio biliary tract cancer review meta analysis background platelet lymphocyte ratio plr found predict clinical outcomes multiple malignancies aim study assess prognostic value pretreatment plr biliary tract cancer btc methods searched medline embase cochrane databases identify studies evaluating prognostic significance pretreatment plr btc end points overall survival os recurrence free survival rfs pooled hazard ratios hrs odds ratios ors 95 confidence intervals cis calculated using fixed effects random effects models results total eleven studies comprising 2392 patients included study pooled results showed elevated plr significantly associated decreased overall survival hr 1 59 95 confidence interval ci 1 42 1 78 p 0 001 recurrence free survival hr 1 53 95 ci 1 16 2 00 p 0 002 subgroup analyses suggested high plr predicted decreased os patient btc regardless sample size 200 200 treatment methods surgery mixed chemotherapy tumor stage mixed metastatic analysis methods univariate multivariate cut values 150 150 nos score 7 7 conclusions elevated pretreatment plr may unfavorable prognostic factor clinical outcomes patients biliary tract cancer pubmed","probabilities":0.9799733,"Title":"Platelet to lymphocyte ratio in biliary tract cancer: Review and meta-analysis","Abstract":"BACKGROUND: The platelet to lymphocyte ratio (PLR) has been found to predict clinical outcomes in multiple malignancies. The aim of this study was to assess the prognostic value of pretreatment PLR in biliary tract cancer (BTC). METHODS: We searched the MEDLINE, EMBASE, and Cochrane databases to identify studies evaluating the prognostic significance of pretreatment PLR in BTC. The end points were overall survival (OS), recurrence-free survival (RFS). Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects/random-effects models. RESULTS: A total of eleven studies comprising 2392 patients were included in the study. Pooled results showed that elevated PLR was significantly associated with decreased overall survival (HR: 1.59, 95% confidence interval [CI]: 1.42-1.78, p<0.001) and recurrence-free survival (HR: 1.53, 95% CI: 1.16-2.00, p=0.002). Subgroup analyses suggested that a high PLR predicted decreased OS in patient with BTC, regardless of sample size (<200 or ≥200), treatment methods (surgery, mixed, or chemotherapy), tumor stage (mixed or metastatic), analysis methods (univariate or multivariate), cut-off values (<150 or ≥150), and NOS score (<7 or ≥7). CONCLUSIONS: Elevated pretreatment PLR may be an unfavorable prognostic factor for clinical outcomes in patients with biliary tract cancer.","Source":"PubMed","category":"HUMAN","training_data":"Platelet to lymphocyte ratio in biliary tract cancer: Review and meta-analysis BACKGROUND: The platelet to lymphocyte ratio (PLR) has been found to predict clinical outcomes in multiple malignancies. The aim of this study was to assess the prognostic value of pretreatment PLR in biliary tract cancer (BTC). METHODS: We searched the MEDLINE, EMBASE, and Cochrane databases to identify studies evaluating the prognostic significance of pretreatment PLR in BTC. The end points were overall survival (OS), recurrence-free survival (RFS). Pooled hazard ratios (HRs) or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed-effects/random-effects models. RESULTS: A total of eleven studies comprising 2392 patients were included in the study. Pooled results showed that elevated PLR was significantly associated with decreased overall survival (HR: 1.59, 95% confidence interval [CI]: 1.42-1.78, p<0.001) and recurrence-free survival (HR: 1.53, 95% CI: 1.16-2.00, p=0.002). Subgroup analyses suggested that a high PLR predicted decreased OS in patient with BTC, regardless of sample size (<200 or ≥200), treatment methods (surgery, mixed, or chemotherapy), tumor stage (mixed or metastatic), analysis methods (univariate or multivariate), cut-off values (<150 or ≥150), and NOS score (<7 or ≥7). CONCLUSIONS: Elevated pretreatment PLR may be an unfavorable prognostic factor for clinical outcomes in patients with biliary tract cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"inhibition active autophagy induces apoptosis increases chemosensitivity cholangiocarcinoma intrahepatic cholangiocellular carcinomas iccs usually fatal neoplasms originating bile duct epithelia however many cholangiocarcinoma cells shown resistant chemotherapeutic drugs induce cell apoptosis role autophagy therapeutic value autophagy associated genes largely unknown icc showed autophagy activated nutrient starvation xenograft cholangiocarcinoma cells furthermore expression autophagic genes autophagic activity higher clinical icc specimens normal cholangiocytes separated laser capture microdissection inhibition autophagy autophagy inhibitors sirna cholangiocarcinoma cells showed detention proliferation increase apoptosis nutrient starvation addition autophagy inhibitor treatment knockdown beclin 1 suppressed tumor growth sensitized icc cells chemotherapeutic agent induced cell death conclusion data showed autophagy activated icc inactivation autophagy may lead cell apoptosis enhance chemotherapy sensitivity stn","probabilities":0.9467213,"Title":"Inhibition Of Active Autophagy Induces Apoptosis And Increases Chemosensitivity In Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocellular carcinomas (ICCs) are usually fatal neoplasms originating from bile duct epithelia. However, many cholangiocarcinoma cells are shown to be resistant to chemotherapeutic drugs, which induce cell apoptosis. The role of autophagy and the therapeutic value of autophagy-associated genes are largely unknown in ICC. Here, we showed that autophagy was activated in nutrient starvation and xenograft cholangiocarcinoma cells. Furthermore, expression of autophagic genes and their autophagic activity were higher in clinical ICC specimens than that in normal cholangiocytes separated by laser capture microdissection. Inhibition of autophagy by autophagy inhibitors or siRNA, cholangiocarcinoma cells showed detention of proliferation and increase of apoptosis during nutrient starvation. In addition, autophagy inhibitor treatment or knockdown of beclin 1 suppressed tumor growth and sensitized ICC cells to chemotherapeutic agent-induced cell death. In conclusion, our data showed that autophagy is activated in ICC, and inactivation of autophagy may lead to cell apoptosis and enhance chemotherapy sensitivity.","Source":"STN","category":"ANIMAL","training_data":"Inhibition Of Active Autophagy Induces Apoptosis And Increases Chemosensitivity In Cholangiocarcinoma Intrahepatic cholangiocellular carcinomas (ICCs) are usually fatal neoplasms originating from bile duct epithelia. However, many cholangiocarcinoma cells are shown to be resistant to chemotherapeutic drugs, which induce cell apoptosis. The role of autophagy and the therapeutic value of autophagy-associated genes are largely unknown in ICC. Here, we showed that autophagy was activated in nutrient starvation and xenograft cholangiocarcinoma cells. Furthermore, expression of autophagic genes and their autophagic activity were higher in clinical ICC specimens than that in normal cholangiocytes separated by laser capture microdissection. Inhibition of autophagy by autophagy inhibitors or siRNA, cholangiocarcinoma cells showed detention of proliferation and increase of apoptosis during nutrient starvation. In addition, autophagy inhibitor treatment or knockdown of beclin 1 suppressed tumor growth and sensitized ICC cells to chemotherapeutic agent-induced cell death. In conclusion, our data showed that autophagy is activated in ICC, and inactivation of autophagy may lead to cell apoptosis and enhance chemotherapy sensitivity. STN","prediction_labels":"ANIMAL"},{"cleaned":"factors predicting surgical resection patients intrahepatic cholangiocarcinoma cirrhosis investigate potential factors affect outcome patients intrahepatic cholangiocarcinomas icc cirrhosis retrospectively reviewed clinical data pathological features 58 patients icc cirrhosis underwent liver resection july 2000 march 2008 analyzed prognostic risk factors means univariate multivariate analyses overall morbidity mortality 40 3 3 respectively overall median survival 24 months 1 3 5 year actuarial survival rates 53 18 10 respectively univariate analysis showed child pugh classification hypoalbuminemia vascular invasion lymphnodes metastasis tumor nodes metastasis tnm staging system positive surgical margins high perioperative blood transfusion volumes significantly associated poor survival multivariate analysis confirmed hypoalbuminemia vascular invasion positive surgical margins high perioperative blood transfusion volume survival related hazard ratios hr 2 58 3 12 3 57 1 98 respectively surgical resection effective treatment patients affected icc cirrhosis predictive factors including hypoalbuminemia vascular invasion positive surgical margins high perioperative blood transfusion volumes related poor survival pubmed","probabilities":0.9799733,"Title":"Factors predicting surgical resection in patients with intrahepatic cholangiocarcinoma and cirrhosis","Abstract":"Here, we investigate the potential factors that affect the outcome of patients with intrahepatic cholangiocarcinomas (ICC) and cirrhosis. We retrospectively reviewed the clinical data and pathological features of 58 patients with ICC and cirrhosis who underwent liver resection between July 2000 and March 2008, and analyzed the prognostic risk factors by means of univariate and multivariate analyses. The overall morbidity and mortality were 40% and 3.3%, respectively. The overall median survival was 24 months, and the 1-, 3-, and 5-year actuarial survival rates were 53%, 18%, and 10%, respectively. Univariate analysis showed that Child-Pugh classification, hypoalbuminemia, vascular invasion, lymphnodes metastasis, tumor-nodes-metastasis (TNM) staging system, positive surgical margins, and high perioperative blood transfusion volumes were all significantly associated with poor survival. Multivariate analysis confirmed that hypoalbuminemia, vascular invasion, positive surgical margins, and high perioperative blood transfusion volume were survival related, with hazard ratios (HR) of 2.58, 3.12, 3.57, and 1.98, respectively. Surgical resection is an effective treatment for patients affected by ICC and cirrhosis. Predictive factors, including hypoalbuminemia, vascular invasion, positive surgical margins, and high perioperative blood transfusion volumes are all related to poor survival.","Source":"PubMed","category":"HUMAN","training_data":"Factors predicting surgical resection in patients with intrahepatic cholangiocarcinoma and cirrhosis Here, we investigate the potential factors that affect the outcome of patients with intrahepatic cholangiocarcinomas (ICC) and cirrhosis. We retrospectively reviewed the clinical data and pathological features of 58 patients with ICC and cirrhosis who underwent liver resection between July 2000 and March 2008, and analyzed the prognostic risk factors by means of univariate and multivariate analyses. The overall morbidity and mortality were 40% and 3.3%, respectively. The overall median survival was 24 months, and the 1-, 3-, and 5-year actuarial survival rates were 53%, 18%, and 10%, respectively. Univariate analysis showed that Child-Pugh classification, hypoalbuminemia, vascular invasion, lymphnodes metastasis, tumor-nodes-metastasis (TNM) staging system, positive surgical margins, and high perioperative blood transfusion volumes were all significantly associated with poor survival. Multivariate analysis confirmed that hypoalbuminemia, vascular invasion, positive surgical margins, and high perioperative blood transfusion volume were survival related, with hazard ratios (HR) of 2.58, 3.12, 3.57, and 1.98, respectively. Surgical resection is an effective treatment for patients affected by ICC and cirrhosis. Predictive factors, including hypoalbuminemia, vascular invasion, positive surgical margins, and high perioperative blood transfusion volumes are all related to poor survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"kras tp53 mutations cause cholangiocyte hepatocyte derived cholangiocarcinoma intrahepatic cholangiocarcinoma icca primary liver cancer epidemiologically linked liver injury poorly understood incipient stages lacks early diagnostics effective therapies icca conventionally thought arise biliary tract studies suggested hepatocytes biliary cells cholangiocytes may give rise icca consistent plasticity cell lineages primary liver carcinomas exhibit phenotypic range hepatocellular carcinoma hcc icca intermediates along spectrum generated mouse models examine consequence targeting mutant kras tp53 common alterations human icca different adult liver cell types selective induction mutations sox9 population predominantly consisting mature cholangiocytes resulted icca emerging premalignant biliary intraepithelial neoplasia bilin contrast adult hepatocytes relatively refractory mutations formed rare hcc context injury accelerated hepatocyte derived tumorigenesis promoted phenotypic switch icca bilin precursor lesions absent hepatocyte derived icca models pointing toward distinct direct emergence malignant cholangiocytic phenotype injured oncogenically primed hepatocytes tp53 loss enhanced reprogramming hepatocytes cholangiocytes may represent mechanism facilitating formation hepatocyte derived icca overall work shows icca driven kras tp53 may originate mature cholangiocytes hepatocytes factors chronic liver injury underlying genetic mutations determine path progression resulting cancer phenotype significance histopathogenesis biliary tract cancer driven tp53 kras mutations differentially impacted cell origin within mature liver well major epidemiologic risk factors cancer res 78 16 4445 51 2018 aacr stn","probabilities":0.9467213,"Title":"Kras And Tp53 Mutations Cause Cholangiocyte- And Hepatocyte-Derived Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (iCCA) is a primary liver cancer epidemiologically linked with liver injury, which has poorly understood incipient stages and lacks early diagnostics and effective therapies. While iCCA is conventionally thought to arise from the biliary tract, studies have suggested that both hepatocytes and biliary cells (cholangiocytes) may give rise to iCCA. Consistent with the plasticity of these cell lineages, primary liver carcinomas exhibit a phenotypic range from hepatocellular carcinoma (HCC) to iCCA, with intermediates along this spectrum. Here, we generated mouse models to examine the consequence of targeting mutant Kras and Tp53, common alterations in human iCCA, to different adult liver cell types. Selective induction of these mutations in the SOX9+ population, predominantly consisting of mature cholangiocytes, resulted in iCCA emerging from premalignant biliary intraepithelial neoplasia (BilIN). In contrast, adult hepatocytes were relatively refractory to these mutations and formed rare HCC. In this context, injury accelerated hepatocyte-derived tumorigenesis and promoted a phenotypic switch to iCCA. BilIN precursor lesions were absent in the hepatocyte-derived iCCA models, pointing toward distinct and direct emergence of a malignant cholangiocytic phenotype from injured, oncogenically primed hepatocytes. Tp53 loss enhanced the reprogramming of hepatocytes to cholangiocytes, which may represent a mechanism facilitating formation of hepatocyte-derived iCCA. Overall, our work shows iCCA driven by Kras and Tp53 may originate from both mature cholangiocytes and hepatocytes, and factors such as chronic liver injury and underlying genetic mutations determine the path of progression and resulting cancer phenotype.Significance: The histopathogenesis of biliary tract cancer, driven by Tp53 and Kras mutations, can be differentially impacted by the cell of origin within the mature liver as well by major epidemiologic risk factors. Cancer Res; 78(16); 4445-51. ©2018 AACR.","Source":"STN","category":"ANIMAL","training_data":"Kras And Tp53 Mutations Cause Cholangiocyte- And Hepatocyte-Derived Cholangiocarcinoma Intrahepatic cholangiocarcinoma (iCCA) is a primary liver cancer epidemiologically linked with liver injury, which has poorly understood incipient stages and lacks early diagnostics and effective therapies. While iCCA is conventionally thought to arise from the biliary tract, studies have suggested that both hepatocytes and biliary cells (cholangiocytes) may give rise to iCCA. Consistent with the plasticity of these cell lineages, primary liver carcinomas exhibit a phenotypic range from hepatocellular carcinoma (HCC) to iCCA, with intermediates along this spectrum. Here, we generated mouse models to examine the consequence of targeting mutant Kras and Tp53, common alterations in human iCCA, to different adult liver cell types. Selective induction of these mutations in the SOX9+ population, predominantly consisting of mature cholangiocytes, resulted in iCCA emerging from premalignant biliary intraepithelial neoplasia (BilIN). In contrast, adult hepatocytes were relatively refractory to these mutations and formed rare HCC. In this context, injury accelerated hepatocyte-derived tumorigenesis and promoted a phenotypic switch to iCCA. BilIN precursor lesions were absent in the hepatocyte-derived iCCA models, pointing toward distinct and direct emergence of a malignant cholangiocytic phenotype from injured, oncogenically primed hepatocytes. Tp53 loss enhanced the reprogramming of hepatocytes to cholangiocytes, which may represent a mechanism facilitating formation of hepatocyte-derived iCCA. Overall, our work shows iCCA driven by Kras and Tp53 may originate from both mature cholangiocytes and hepatocytes, and factors such as chronic liver injury and underlying genetic mutations determine the path of progression and resulting cancer phenotype.Significance: The histopathogenesis of biliary tract cancer, driven by Tp53 and Kras mutations, can be differentially impacted by the cell of origin within the mature liver as well by major epidemiologic risk factors. Cancer Res; 78(16); 4445-51. ©2018 AACR. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic relevance tumor hypoxia markers resected carcinoma gallbladder background intratumoral hypoxia suggested drive aggressive tumor behavior aim define whether markers tumor hypoxia predictors outcome patients gallbladder carcinoma patients methods 1996 2006 34 patients underwent resection gallbladder carcinoma median follow 12 6 months immunohistochemical stains vegf hif1 glut1 glut3 ca9 egfr performed archival tissue immunohistochemical results correlated clinical histopathological parameters cumulative overall survival os rates estimated using kaplan meier method multivariable cox regression models used identify predictors os results median os 11 9 iqr 3 4 22 0 months ubiquitous vegf staining observed gallbladder carcinomas high 50 tumor cells egfr expression associated worse os p0 03 ca9 expression less prevalent poorly differentiated tumors p0 02 glut3 glut1 hif1 expression associated survival correlate presence lymph node metastasis p0 02 tumor differentiation p0 04 tumor stage p0 03 respectively high egfr expression tnm stage preoperative serum ca19 9 retained independent predictors os multivariable analysis conclusion gallbladder cancer high expression egfr independent predictor survival stn","probabilities":0.7966102,"Title":"The Prognostic Relevance Of Tumor Hypoxia Markers In Resected Carcinoma Of The Gallbladder","Abstract":"Background: Intratumoral hypoxia has been suggested to drive more aggressive tumor behavior. Our aim was to define whether markers of tumor hypoxia are predictors of outcome in patients with gallbladder carcinoma. \r\n\r\n Patients and methods: From 1996 to 2006, 34 patients underwent resection for gallbladder carcinoma. The median follow-up was 12.6 months. Immunohistochemical stains for VEGF, HIF1α, GLUT1, GLUT3, CA9 and EGFR were performed on archival tissue. Immunohistochemical results were correlated with clinical and histopathological parameters. Cumulative overall survival (OS) rates were estimated using the Kaplan-Meier method. Multivariable Cox regression models were used to identify predictors of OS. \r\n\r\n Results: The median OS was 11.9 (IQR: 3.4-22.0) months. Ubiquitous VEGF staining was observed in all gallbladder carcinomas. High (>50% of tumor cells) EGFR expression was associated with worse OS (p0.03). CA9 expression was less prevalent in poorly differentiated tumors (p0.02). GLUT3, GLUT1 and HIF1α expression were not associated with survival, but did correlate with the presence of lymph node metastasis (p0.02), tumor differentiation (p0.04) and tumor stage (p0.03) respectively. High EGFR expression, TNM stage and preoperative serum CA19.9 were retained as independent predictors of OS in multivariable analysis. \r\n\r\n Conclusion: In gallbladder cancer high expression of EGFR is an independent predictor of survival.","Source":"STN","category":"HUMAN","training_data":"The Prognostic Relevance Of Tumor Hypoxia Markers In Resected Carcinoma Of The Gallbladder Background: Intratumoral hypoxia has been suggested to drive more aggressive tumor behavior. Our aim was to define whether markers of tumor hypoxia are predictors of outcome in patients with gallbladder carcinoma. \r\n\r\n Patients and methods: From 1996 to 2006, 34 patients underwent resection for gallbladder carcinoma. The median follow-up was 12.6 months. Immunohistochemical stains for VEGF, HIF1α, GLUT1, GLUT3, CA9 and EGFR were performed on archival tissue. Immunohistochemical results were correlated with clinical and histopathological parameters. Cumulative overall survival (OS) rates were estimated using the Kaplan-Meier method. Multivariable Cox regression models were used to identify predictors of OS. \r\n\r\n Results: The median OS was 11.9 (IQR: 3.4-22.0) months. Ubiquitous VEGF staining was observed in all gallbladder carcinomas. High (>50% of tumor cells) EGFR expression was associated with worse OS (p0.03). CA9 expression was less prevalent in poorly differentiated tumors (p0.02). GLUT3, GLUT1 and HIF1α expression were not associated with survival, but did correlate with the presence of lymph node metastasis (p0.02), tumor differentiation (p0.04) and tumor stage (p0.03) respectively. High EGFR expression, TNM stage and preoperative serum CA19.9 were retained as independent predictors of OS in multivariable analysis. \r\n\r\n Conclusion: In gallbladder cancer high expression of EGFR is an independent predictor of survival. STN","prediction_labels":"HUMAN"},{"cleaned":"alterations p53 gene gallbladder cancer patients north india background mutations p53 gene found majority human malignancies usually occur exons 5 6 7 8 mutated p53 protein stable gets accumulated cells induce host develop anti p53 antibodies sera cancer patients aim study aimed observe frequency nature mutations exons 5 8 p53 gene evaluate correlation prevalence serum p53 antibodies indian patients gallbladder cancer gbc methods mutation studies done cancer tissues obtained 62 patients proven gbc 40 cytologically proven cases 22 resected gallbladder cancer tissues polymerase chain reaction pcr restriction fragment length analysis rflp single strand conformation polymorphism sscp presence serum p53 antibodies determined using highly specific enzyme linked immunosorbent assay elisa kit 50 patients gbc 30 patients cholelithiasis clinicopathologic characteristics patients given attention results antibodies p53 protein present serum 34 17 50 gbc patients 3 3 1 30 patients cholelithiasis p 0 018 rflp failed detect common mutations exons 5 8 p53 gene 62 samples using sscp analysis detect frameshift mutation p53 gene 2 22 9 1 gbc cases mutated samples sequenced found insertion adenine codon 271 gag exon 8 region conclusion results show 1 3rd north indian patients gbc antibodies p53 protein commonest identifiable alteration p53 gene frameshift mutation codon 271 stn","probabilities":1.0,"Title":"Alterations Of P53 Gene In Gallbladder Cancer Patients Of North India","Abstract":"Background: Mutations in p53 gene are found in a majority of human malignancies and usually occur in the exons 5, 6, 7 and 8. Mutated p53 protein is more stable and gets accumulated in the cells that induce the host to develop anti-p53 antibodies in sera of cancer patients. \r\n\r\n Aim: This study is aimed to observe the frequency and nature of mutations in exons 5-8 of p53 gene and to evaluate its correlation with prevalence of serum p53 antibodies in Indian patients with gallbladder cancer (GBC). \r\n\r\n Methods: Mutation studies were done in cancer tissues obtained from 62 patients with proven GBC (40 cytologically proven cases and 22 resected gallbladder cancer tissues) by polymerase chain reaction (PCR), restriction fragment length analysis (RFLP) and single strand conformation polymorphism (SSCP). Presence of serum p53 antibodies was determined using highly specific enzyme linked immunosorbent assay (ELISA) kit in 50 patients with GBC and 30 patients of cholelithiasis. Clinicopathologic characteristics of these patients were given attention. \r\n\r\n Results: Antibodies to p53 protein was present in the serum in 34% (17/50) of GBC patients and in 3.3% (1/30) patients with cholelithiasis (p < 0.018). RFLP failed to detect common mutations in the exons 5- 8 of the p53 gene in 62 samples. Using SSCP analysis we could detect frameshift mutation in p53 gene in 2 of 22 (9.1%) GBC cases. Mutated samples were sequenced and found to have insertion of adenine at codon 271 (GAG) in exon 8 region. \r\n\r\n Conclusion: Our results show that 1//3rd of the north Indian patients with GBC have antibodies to p53 protein. The commonest identifiable alteration in the p53 gene was a frameshift mutation at codon 271.","Source":"STN","category":"ANIMAL","training_data":"Alterations Of P53 Gene In Gallbladder Cancer Patients Of North India Background: Mutations in p53 gene are found in a majority of human malignancies and usually occur in the exons 5, 6, 7 and 8. Mutated p53 protein is more stable and gets accumulated in the cells that induce the host to develop anti-p53 antibodies in sera of cancer patients. \r\n\r\n Aim: This study is aimed to observe the frequency and nature of mutations in exons 5-8 of p53 gene and to evaluate its correlation with prevalence of serum p53 antibodies in Indian patients with gallbladder cancer (GBC). \r\n\r\n Methods: Mutation studies were done in cancer tissues obtained from 62 patients with proven GBC (40 cytologically proven cases and 22 resected gallbladder cancer tissues) by polymerase chain reaction (PCR), restriction fragment length analysis (RFLP) and single strand conformation polymorphism (SSCP). Presence of serum p53 antibodies was determined using highly specific enzyme linked immunosorbent assay (ELISA) kit in 50 patients with GBC and 30 patients of cholelithiasis. Clinicopathologic characteristics of these patients were given attention. \r\n\r\n Results: Antibodies to p53 protein was present in the serum in 34% (17/50) of GBC patients and in 3.3% (1/30) patients with cholelithiasis (p < 0.018). RFLP failed to detect common mutations in the exons 5- 8 of the p53 gene in 62 samples. Using SSCP analysis we could detect frameshift mutation in p53 gene in 2 of 22 (9.1%) GBC cases. Mutated samples were sequenced and found to have insertion of adenine at codon 271 (GAG) in exon 8 region. \r\n\r\n Conclusion: Our results show that 1//3rd of the north Indian patients with GBC have antibodies to p53 protein. The commonest identifiable alteration in the p53 gene was a frameshift mutation at codon 271. STN","prediction_labels":"ANIMAL"},{"cleaned":"dabrafenib preclinical characterization increased efficacy combined trametinib braf mek tool combination reduced skin lesions mitogen activated protein kinase mapk pathway activation implicated many types human cancer braf mutations constitutively activate mapk signalling bypass need upstream stimuli occur high prevalence melanoma colorectal carcinoma ovarian cancer papillary thyroid carcinoma cholangiocarcinoma report characterize novel potent selective braf inhibitor dabrafenib gsk2118436 cellular inhibition brafv600e kinase activity dabrafenib resulted decreased mek erk phosphorylation inhibition cell proliferation initial g1 cell cycle arrest followed cell death brafv600e containing xenograft model human melanoma orally administered dabrafenib inhibited erk activation downregulated ki67 upregulated p27 leading tumor growth inhibition however reported braf inhibitors dabrafenib also induced mapk pathway activation wild type braf cells craf raf1 signalling potentially explaining squamous cell carcinomas keratoacanthomas arising patients treated braf inhibitors addressing issue showed concomitant administration braf mek inhibitors abrogated paradoxical braf inhibitor induced mapk signalling cells reduced occurrence skin lesions rats enhanced inhibition human tumor xenograft growth mouse models taken together findings offer preclinical proof concept dabrafenib specific highly efficacious braf inhibitor provide evidence potential clinical benefits used combination mek inhibitor google scholar","probabilities":0.9467213,"Title":"Dabrafenib; Preclinical Characterization Increased Efficacy When Combined With Trametinib While Braf/Mek Tool Combination Reduced Skin Lesions","Abstract":"Mitogen-Activated Protein Kinase (MAPK) pathway activation has been implicated in many types of human cancer. BRAF mutations that constitutively activate MAPK signalling and bypass the need for upstream stimuli occur with high prevalence in melanoma, colorectal carcinoma, ovarian cancer, papillary thyroid carcinoma, and cholangiocarcinoma. In this report we characterize the novel, potent, and selective BRAF inhibitor, dabrafenib (GSK2118436). Cellular inhibition of BRAFV600E kinase activity by dabrafenib resulted in decreased MEK and ERK phosphorylation and inhibition of cell proliferation through an initial G1 cell cycle arrest, followed by cell death. In a BRAFV600E-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition. However, as reported for other BRAF inhibitors, dabrafenib also induced MAPK pathway activation in wild-type BRAF cells through CRAF (RAF1) signalling, potentially explaining the squamous cell carcinomas and keratoacanthomas arising in patients treated with BRAF inhibitors. In addressing this issue, we showed that concomitant administration of BRAF and MEK inhibitors abrogated paradoxical BRAF inhibitor-induced MAPK signalling in cells, reduced the occurrence of skin lesions in rats, and enhanced the inhibition of human tumor xenograft growth in mouse models. Taken together, our findings offer preclinical proof of concept for dabrafenib as a specific and highly efficacious BRAF inhibitor and provide evidence for its potential clinical benefits when used in combination with a MEK inhibitor.","Source":"Google Scholar","category":"ANIMAL","training_data":"Dabrafenib; Preclinical Characterization Increased Efficacy When Combined With Trametinib While Braf/Mek Tool Combination Reduced Skin Lesions Mitogen-Activated Protein Kinase (MAPK) pathway activation has been implicated in many types of human cancer. BRAF mutations that constitutively activate MAPK signalling and bypass the need for upstream stimuli occur with high prevalence in melanoma, colorectal carcinoma, ovarian cancer, papillary thyroid carcinoma, and cholangiocarcinoma. In this report we characterize the novel, potent, and selective BRAF inhibitor, dabrafenib (GSK2118436). Cellular inhibition of BRAFV600E kinase activity by dabrafenib resulted in decreased MEK and ERK phosphorylation and inhibition of cell proliferation through an initial G1 cell cycle arrest, followed by cell death. In a BRAFV600E-containing xenograft model of human melanoma, orally administered dabrafenib inhibited ERK activation, downregulated Ki67, and upregulated p27, leading to tumor growth inhibition. However, as reported for other BRAF inhibitors, dabrafenib also induced MAPK pathway activation in wild-type BRAF cells through CRAF (RAF1) signalling, potentially explaining the squamous cell carcinomas and keratoacanthomas arising in patients treated with BRAF inhibitors. In addressing this issue, we showed that concomitant administration of BRAF and MEK inhibitors abrogated paradoxical BRAF inhibitor-induced MAPK signalling in cells, reduced the occurrence of skin lesions in rats, and enhanced the inhibition of human tumor xenograft growth in mouse models. Taken together, our findings offer preclinical proof of concept for dabrafenib as a specific and highly efficacious BRAF inhibitor and provide evidence for its potential clinical benefits when used in combination with a MEK inhibitor. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"factors influencing lymph node metastasis patients ampullary adenocarcinoma aim cases ampullary carcinoma lymph node involvement affects selection treatment strategies study aimed identify clinicopathologic features ampullary carcinoma lymph node metastases methods records 74 consecutive patients ampullary adenocarcinoma underwent pancreaticoduodenectomy pd regional lymph node dissection retrospectively analyzed results twenty two patients 30 lymph node metastasis significantly worse survival resection without lymph node metastasis p 0 017 univariate analyses revealed preoperative biliary drainage elevated serum carbohydrate antigen 19 9 36 u ml moderate poor pathologic grade g2 3 perineural vascular lymphatic pancreas duodenal invasion category significantly associated lymph node metastasis multivariate analysis pathologic grade g2 3 remained significantly associated lymph node metastasis hazard ratio 6 51 p 0 035 sub classified analysis category lymph node metastasis found 5 22 cases 22 7 t1 tumors four five cases lymph node metastases dominant g2 3 component whereas 2 17 cases without lymph node metastases g2 3 component t1 tumors p 0 0036 conclusions pathologic grade g2 3 significantly independently associated lymph node metastasis also significant predictor t1 tumor cases pubmed","probabilities":0.9799733,"Title":"Factors influencing lymph node metastasis in patients with ampullary adenocarcinoma","Abstract":"AIM: In cases of ampullary carcinoma, lymph node involvement affects the selection of treatment strategies. This study aimed to identify clinicopathologic features of ampullary carcinoma with lymph node metastases. METHODS: The records of 74 consecutive patients with ampullary adenocarcinoma who underwent pancreaticoduodenectomy (PD) with regional lymph node dissection were retrospectively analyzed. RESULTS: Twenty-two patients (30%) with lymph node metastasis had significantly worse survival after resection than those without lymph node metastasis (p = 0.017). Univariate analyses revealed that preoperative biliary drainage; elevated serum carbohydrate antigen 19-9 (≥36 U/ml); moderate-to-poor pathologic grade (G2/3); perineural, vascular, lymphatic, pancreas, and duodenal invasion; and T category were significantly associated with lymph node metastasis. In multivariate analysis, only pathologic grade (G2/3) remained significantly associated with lymph node metastasis (hazard ratio, 6.51; p = 0.035). In sub-classified analysis for T category, lymph node metastasis was found in 5 of 22 cases (22.7%) of T1 tumors. Four of five cases with lymph node metastases had a dominant G2/3 component, whereas only 2 of 17 cases without lymph node metastases had a G2/3 component in T1 tumors (p = 0.0036). CONCLUSIONS: Pathologic grade (G2/3) was significantly and independently associated with lymph node metastasis and was also a significant predictor in T1 tumor cases.","Source":"PubMed","category":"HUMAN","training_data":"Factors influencing lymph node metastasis in patients with ampullary adenocarcinoma AIM: In cases of ampullary carcinoma, lymph node involvement affects the selection of treatment strategies. This study aimed to identify clinicopathologic features of ampullary carcinoma with lymph node metastases. METHODS: The records of 74 consecutive patients with ampullary adenocarcinoma who underwent pancreaticoduodenectomy (PD) with regional lymph node dissection were retrospectively analyzed. RESULTS: Twenty-two patients (30%) with lymph node metastasis had significantly worse survival after resection than those without lymph node metastasis (p = 0.017). Univariate analyses revealed that preoperative biliary drainage; elevated serum carbohydrate antigen 19-9 (≥36 U/ml); moderate-to-poor pathologic grade (G2/3); perineural, vascular, lymphatic, pancreas, and duodenal invasion; and T category were significantly associated with lymph node metastasis. In multivariate analysis, only pathologic grade (G2/3) remained significantly associated with lymph node metastasis (hazard ratio, 6.51; p = 0.035). In sub-classified analysis for T category, lymph node metastasis was found in 5 of 22 cases (22.7%) of T1 tumors. Four of five cases with lymph node metastases had a dominant G2/3 component, whereas only 2 of 17 cases without lymph node metastases had a G2/3 component in T1 tumors (p = 0.0036). CONCLUSIONS: Pathologic grade (G2/3) was significantly and independently associated with lymph node metastasis and was also a significant predictor in T1 tumor cases. PubMed","prediction_labels":"HUMAN"},{"cleaned":"immunohistochemical analysis mtor pathway intrahepatic cholangiocarcinoma aim study evaluate expression activated mammalian rapamycin mtor downstream effectors phosphorylated p70 ribosomal protein s6 kinase p70s6k eukaryotic initiation factor 4e binding protein 1 4ebp1 intrahepatic cholangiocarcinomas icc order strengthen rationale targeted therapy using mtor inhibitors patients icc p mtor ser 2448 p 4ebp1 thr 70 p p70s6k thr 389 detected 77 primary icc tumors immunohistochemistry high levels p mtor p 4ebp1 p p70s6k expression defined 48 1 37 77 50 6 39 77 51 9 40 77 tumors respectively significant correlation observed mtor pathway proteins overexpression clinicopathological characteristics patient prognosis except high p p70s6k expression correlated poorly differentiated subtype high expression p 4ebp1 predicted poor prognosis icc patients retained independent prognostic factor multivariate analysis conclusion results showed high prevalence activation mtor pathway icc tumors suggesting high proportion icc patients might benefit mtor pathway targeted therapies addition p 4ebp1 phosphorylation thr 70 useful prognostic biomarker icc patients pubmed","probabilities":0.9799733,"Title":"Immunohistochemical analysis of the mTOR pathway in intrahepatic cholangiocarcinoma","Abstract":"The aim of the study was to evaluate the expression of activated mammalian rapamycin (mTOR) and its downstream effectors, phosphorylated p70 ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1), in intrahepatic cholangiocarcinomas (ICC), in order to strengthen the rationale for targeted therapy using mTOR inhibitors in patients with ICC. p-mTOR (Ser 2448), p-4EBP1 (Thr 70) and p-p70S6K (Thr 389) were detected in 77 primary ICC tumors by immunohistochemistry. High levels of p-mTOR, p-4EBP1 and p-p70S6K expression were defined in 48.1% (37/77), 50.6% (39/77) and 51.9% (40/77) of all tumors, respectively. No significant correlation was observed between mTOR pathway proteins overexpression with clinicopathological characteristics and patient's prognosis, except that high p-p70S6K expression correlated with the poorly differentiated subtype, and high expression of p-4EBP1 predicted poor prognosis in ICC patients and retained an independent prognostic factor in multivariate analysis. In conclusion, our results showed high prevalence of activation of mTOR pathway in ICC tumors, suggesting that a high proportion of ICC patients might benefit from mTOR pathway targeted therapies. In addition, p-4EBP1 phosphorylation at Thr 70 could be a useful prognostic biomarker for ICC patients.","Source":"PubMed","category":"HUMAN","training_data":"Immunohistochemical analysis of the mTOR pathway in intrahepatic cholangiocarcinoma The aim of the study was to evaluate the expression of activated mammalian rapamycin (mTOR) and its downstream effectors, phosphorylated p70 ribosomal protein S6 kinase (p70S6K) and eukaryotic initiation factor 4E-binding protein 1 (4EBP1), in intrahepatic cholangiocarcinomas (ICC), in order to strengthen the rationale for targeted therapy using mTOR inhibitors in patients with ICC. p-mTOR (Ser 2448), p-4EBP1 (Thr 70) and p-p70S6K (Thr 389) were detected in 77 primary ICC tumors by immunohistochemistry. High levels of p-mTOR, p-4EBP1 and p-p70S6K expression were defined in 48.1% (37/77), 50.6% (39/77) and 51.9% (40/77) of all tumors, respectively. No significant correlation was observed between mTOR pathway proteins overexpression with clinicopathological characteristics and patient's prognosis, except that high p-p70S6K expression correlated with the poorly differentiated subtype, and high expression of p-4EBP1 predicted poor prognosis in ICC patients and retained an independent prognostic factor in multivariate analysis. In conclusion, our results showed high prevalence of activation of mTOR pathway in ICC tumors, suggesting that a high proportion of ICC patients might benefit from mTOR pathway targeted therapies. In addition, p-4EBP1 phosphorylation at Thr 70 could be a useful prognostic biomarker for ICC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival combined hepatocellular cholangiocarcinoma differs race seer database analysis abstract available google scholar","probabilities":0.9799733,"Title":"Survival Of Combined Hepatocellular And Cholangiocarcinoma Differs By Race: A Seer Database Analysis","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Survival Of Combined Hepatocellular And Cholangiocarcinoma Differs By Race: A Seer Database Analysis Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"neoadjuvant chemoradiation therapy perihilar cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"The Neoadjuvant Chemoradiation Therapy For Perihilar Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"The Neoadjuvant Chemoradiation Therapy For Perihilar Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"fibroblast growth factor receptor inhibition induces loss matrix mcl1 necrosis cholangiocarcinoma background aims myeloid cell leukemia 1 mcl1 prosurvival member bcl2 protein family pivotal role human cholangiocarcinoma cca cell survival previously reported fibroblast growth factor receptor fgfr signalling mediates mcl1 dependent survival cca cells vitro vivo however mode mechanisms cell death model delineated methods human cca cell lines treated pan fgfr inhibitor ly2874455 mode cell death examined several complementary assays mitochondrial oxidative metabolism examined using xf24 extracellular flux analyser efficiency fgfr inhibition patient derived xenografts pdx also assessed results cca cells expressed two species mcl1 full length form localised outer mitochondrial membrane n terminus truncated species compartmentalised within mitochondrial matrix pan fgfr inhibitor ly2874455 induced non apoptotic cell death cca cell lines associated cellular depletion mcl1 species cell death accompanied failure mitochondrial oxidative metabolism consistent necrosis enforced expression n terminus truncated mcl1 targeted mitochondrial matrix full length mcl1 targeted outer mitochondrial membrane rescued cell death mitochondrial function ly2874455 treatment pdx bearing mice associated tumour cell loss mcl1 cell necrosis conclusions fgfr inhibition induces loss matrix mcl1 resulting cell necrosis observations support heretofore unidentified alternative mcl1 survival function namely prevention cell necrosis implications treatment human cca lay summary herein report therapeutic inhibition cell receptor expressed bile duct cancer cells resulted loss critical survival protein termed mcl1 cellular depletion mcl1 resulted death cancer cells process characterised cell rupture cell death process stimulate immune system implications combination therapy using receptor inhibition immunotherapy stn","probabilities":0.9467213,"Title":"Fibroblast Growth Factor Receptor Inhibition Induces Loss Of Matrix Mcl1 And Necrosis In Cholangiocarcinoma","Abstract":"Background & aims: Myeloid cell leukemia 1 (MCL1), a prosurvival member of the BCL2 protein family, has a pivotal role in human cholangiocarcinoma (CCA) cell survival. We previously reported that fibroblast growth factor receptor (FGFR) signalling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. \r\n\r\n Methods: Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays. Mitochondrial oxidative metabolism was examined using a XF24 extracellular flux analyser. The efficiency of FGFR inhibition in patient-derived xenografts (PDX) was also assessed. \r\n\r\n Results: CCA cells expressed two species of MCL1, a full-length form localised to the outer mitochondrial membrane, and an N terminus-truncated species compartmentalised within the mitochondrial matrix. The pan-FGFR inhibitor LY2874455 induced non-apoptotic cell death in the CCA cell lines associated with cellular depletion of both MCL1 species. The cell death was accompanied by failure of mitochondrial oxidative metabolism and was most consistent with necrosis. Enforced expression of N terminus-truncated MCL1 targeted to the mitochondrial matrix, but not full-length MCL1 targeted to the outer mitochondrial membrane, rescued cell death and mitochondrial function. LY2874455 treatment of PDX-bearing mice was associated with tumour cell loss of MCL1 and cell necrosis. \r\n\r\n Conclusions: FGFR inhibition induces loss of matrix MCL1, resulting in cell necrosis. These observations support a heretofore unidentified, alternative MCL1 survival function, namely prevention of cell necrosis, and have implications for treatment of human CCA. \r\n\r\n Lay summary: Herein, we report that therapeutic inhibition of a cell receptor expressed by bile duct cancer cells resulted in the loss of a critical survival protein termed MCL1. Cellular depletion of MCL1 resulted in the death of the cancer cells by a process characterised by cell rupture. Cell death by this process can stimulate the immune system and has implications for combination therapy using receptor inhibition with immunotherapy.","Source":"STN","category":"ANIMAL","training_data":"Fibroblast Growth Factor Receptor Inhibition Induces Loss Of Matrix Mcl1 And Necrosis In Cholangiocarcinoma Background & aims: Myeloid cell leukemia 1 (MCL1), a prosurvival member of the BCL2 protein family, has a pivotal role in human cholangiocarcinoma (CCA) cell survival. We previously reported that fibroblast growth factor receptor (FGFR) signalling mediates MCL1-dependent survival of CCA cells in vitro and in vivo. However, the mode and mechanisms of cell death in this model were not delineated. \r\n\r\n Methods: Human CCA cell lines were treated with the pan-FGFR inhibitor LY2874455 and the mode of cell death examined by several complementary assays. Mitochondrial oxidative metabolism was examined using a XF24 extracellular flux analyser. The efficiency of FGFR inhibition in patient-derived xenografts (PDX) was also assessed. \r\n\r\n Results: CCA cells expressed two species of MCL1, a full-length form localised to the outer mitochondrial membrane, and an N terminus-truncated species compartmentalised within the mitochondrial matrix. The pan-FGFR inhibitor LY2874455 induced non-apoptotic cell death in the CCA cell lines associated with cellular depletion of both MCL1 species. The cell death was accompanied by failure of mitochondrial oxidative metabolism and was most consistent with necrosis. Enforced expression of N terminus-truncated MCL1 targeted to the mitochondrial matrix, but not full-length MCL1 targeted to the outer mitochondrial membrane, rescued cell death and mitochondrial function. LY2874455 treatment of PDX-bearing mice was associated with tumour cell loss of MCL1 and cell necrosis. \r\n\r\n Conclusions: FGFR inhibition induces loss of matrix MCL1, resulting in cell necrosis. These observations support a heretofore unidentified, alternative MCL1 survival function, namely prevention of cell necrosis, and have implications for treatment of human CCA. \r\n\r\n Lay summary: Herein, we report that therapeutic inhibition of a cell receptor expressed by bile duct cancer cells resulted in the loss of a critical survival protein termed MCL1. Cellular depletion of MCL1 resulted in the death of the cancer cells by a process characterised by cell rupture. Cell death by this process can stimulate the immune system and has implications for combination therapy using receptor inhibition with immunotherapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"association nonalcoholic fatty liver disease liver cancer aim investigate association nonalcoholic fatty liver disease nafld liver cancer nafld prevalence different liver tumors methods retrospective study clinical laboratory histological data 120 patients diagnosed primary secondary hepatic neoplasms treated tertiary center underwent hepatic resection liver transplantation subsequent evaluation explant liver biopsy following criteria used exclude patients study history alcohol abuse hepatitis b c infection tumor detected liver tissue examined histological analysis presence chronic autoimmune hepatitis hemochromatosis wilson disease hepatoblastoma occurrence nafld association known risk factors studied risk factors considered diabetes mellitus impaired glucose tolerance impaired fasting glucose body mass index dyslipidemia arterial hypertension presence reticulin fibers hepatic neoplasms assessed histological analysis using slide mounted specimens stained either hematoxylin eosin masson trichrome silver impregnation analysis tumor free liver parenchyma carried determine association nafld histological grade results difference found association nafld general population 34 2 30 0 respectively 95 ci 25 8 43 4 evaluation cancer type showed nafld prevalent patients liver metastasis colorectal cancer patients hepatocellular carcinoma intrahepatic cholangiocarcinoma 3 99 95 ci 1 78 8 94 p 0 001 vs 0 60 95 ci 0 18 2 01 p 0 406 0 70 95 ci 0 18 2 80 p 0 613 respectively higher prevalence liver fibrosis patients hepatocellular carcinoma 3 50 95 ci 1 06 11 57 p 0 032 evaluation relationship presence nafld nonalcoholic steatohepatitis liver fibrosis risk factors showed significant statistical association tumors studied conclusion nafld common patients liver metastases caused colorectal cancer pubmed","probabilities":0.7966102,"Title":"Association of nonalcoholic fatty liver disease and liver cancer","Abstract":"AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson's disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson's trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the relationship between the presence of NAFLD, nonalcoholic steatohepatitis, and liver fibrosis, and their risk factors, showed no significant statistical association for any of the tumors studied. CONCLUSION: NAFLD is more common in patients with liver metastases caused by colorectal cancer.","Source":"PubMed","category":"HUMAN","training_data":"Association of nonalcoholic fatty liver disease and liver cancer AIM: To investigate the association between nonalcoholic fatty liver disease (NAFLD) and liver cancer, and NAFLD prevalence in different liver tumors. METHODS: This is a retrospective study of the clinical, laboratory and histological data of 120 patients diagnosed with primary or secondary hepatic neoplasms and treated at a tertiary center where they underwent hepatic resection and/or liver transplantation, with subsequent evaluation of the explant or liver biopsy. The following criteria were used to exclude patients from the study: a history of alcohol abuse, hepatitis B or C infection, no tumor detected in the liver tissue examined by histological analysis, and the presence of chronic autoimmune hepatitis, hemochromatosis, Wilson's disease, or hepatoblastoma. The occurrence of NAFLD and the association with its known risk factors were studied. The risk factors considered were diabetes mellitus, impaired glucose tolerance, impaired fasting glucose, body mass index, dyslipidemia, and arterial hypertension. Presence of reticulin fibers in the hepatic neoplasms was assessed by histological analysis using slide-mounted specimens stained with either hematoxylin and eosin or Masson's trichrome and silver impregnation. Analysis of tumor-free liver parenchyma was carried out to determine the association between NAFLD and its histological grade. RESULTS: No difference was found in the association of NAFLD with the general population (34.2% and 30.0% respectively, 95%CI: 25.8-43.4). Evaluation by cancer type showed that NAFLD was more prevalent in patients with liver metastasis of colorectal cancer than in patients with hepatocellular carcinoma and intrahepatic cholangiocarcinoma (OR = 3.99, 95%CI: 1.78-8.94, P < 0.001 vs OR = 0.60, 95%CI: 0.18-2.01, P = 0.406 and OR = 0.70, 95%CI: 0.18-2.80, P = 0.613, respectively). There was a higher prevalence of liver fibrosis in patients with hepatocellular carcinoma (OR = 3.50, 95%CI: 1.06-11.57, P = 0.032). Evaluation of the relationship between the presence of NAFLD, nonalcoholic steatohepatitis, and liver fibrosis, and their risk factors, showed no significant statistical association for any of the tumors studied. CONCLUSION: NAFLD is more common in patients with liver metastases caused by colorectal cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"progranulin predictive factor response chemotherapy advanced biliary tract carcinoma purpose progranulin pgrn characterized autocrine growth survival factor known stimulate proliferation survival several cancer cell types however little known prognostic role pgrn advanced biliary tract cancers btcs methods retrospective analysis performed patients advanced btc received palliative chemotherapy july 2004 november 2014 pgrn expression immunohistochemically evaluated according staining intensity tumor peritumoral cells results total 80 patients 39 intrahepatic 26 extrahepatic 18 gallbladder tumors analyzed median age 64 years range 31 79 48 patients 60 male thirty five patients 44 high tumor pgrn expression pgrn positive trend poorer response chemotherapy patients pgrn positive tumor terms overall response rate 7 vs 18 median follow duration 17 7 months range 4 9 35 1 pgrn positive patients worse progression free survival pfs median 2 7 months compared 5 0 months pgrn negative patients p 0 023 adjusting possible confounding factors including sex age performance status disease status chemotherapy agent multivariate analysis showed pgrn positive tumor prognostic factor independently associated poor pfs hazard ratio 1 69 95 ci 1 02 2 81 p 0 044 conclusion pgrn overexpression significantly associated poor pfs advanced btcs pgrn expression ihc analysis might help predict treatment outcomes provide new target molecular therapy pubmed","probabilities":0.962963,"Title":"Progranulin as a predictive factor of response to chemotherapy in advanced biliary tract carcinoma","Abstract":"PURPOSE: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the proliferation and survival of several cancer cell types. However, little is known about the prognostic role of PGRN in advanced biliary tract cancers (BTCs). METHODS: A retrospective analysis was performed on patients with advanced BTC who received palliative chemotherapy between July 2004 and November 2014. PGRN expression was immunohistochemically evaluated according to staining intensity of tumor and peritumoral cells. RESULTS: A total of 80 patients (39 intrahepatic, 26 extrahepatic, and 18 gallbladder tumors) were analyzed. The median age was 64 years (range 31-79), and 48 patients (60 %) were male. Thirty-five patients (44 %) had high tumor PGRN expression (PGRN positive), and there was a trend of poorer response to chemotherapy in patients with PGRN-positive tumor in terms of overall response rate (7 vs. 18 %). With a median follow-up duration of 17.7 months (range 4.9-35.1), PGRN-positive patients had worse progression-free survival (PFS) with a median of 2.7 months compared to 5.0 months for PGRN-negative patients (P = 0.023). After adjusting for possible confounding factors including sex, age, performance status, disease status, and chemotherapy agent, multivariate analysis showed that PGRN-positive tumor was a prognostic factor independently associated with poor PFS (hazard ratio 1.69, 95 % CI 1.02-2.81; P = 0.044). CONCLUSION: PGRN overexpression was significantly associated with poor PFS in advanced BTCs. PGRN expression by IHC analysis might help predict treatment outcomes and provide a new target for molecular therapy.","Source":"PubMed","category":"HUMAN","training_data":"Progranulin as a predictive factor of response to chemotherapy in advanced biliary tract carcinoma PURPOSE: Progranulin (PGRN), characterized as an autocrine growth and survival factor, is known to stimulate the proliferation and survival of several cancer cell types. However, little is known about the prognostic role of PGRN in advanced biliary tract cancers (BTCs). METHODS: A retrospective analysis was performed on patients with advanced BTC who received palliative chemotherapy between July 2004 and November 2014. PGRN expression was immunohistochemically evaluated according to staining intensity of tumor and peritumoral cells. RESULTS: A total of 80 patients (39 intrahepatic, 26 extrahepatic, and 18 gallbladder tumors) were analyzed. The median age was 64 years (range 31-79), and 48 patients (60 %) were male. Thirty-five patients (44 %) had high tumor PGRN expression (PGRN positive), and there was a trend of poorer response to chemotherapy in patients with PGRN-positive tumor in terms of overall response rate (7 vs. 18 %). With a median follow-up duration of 17.7 months (range 4.9-35.1), PGRN-positive patients had worse progression-free survival (PFS) with a median of 2.7 months compared to 5.0 months for PGRN-negative patients (P = 0.023). After adjusting for possible confounding factors including sex, age, performance status, disease status, and chemotherapy agent, multivariate analysis showed that PGRN-positive tumor was a prognostic factor independently associated with poor PFS (hazard ratio 1.69, 95 % CI 1.02-2.81; P = 0.044). CONCLUSION: PGRN overexpression was significantly associated with poor PFS in advanced BTCs. PGRN expression by IHC analysis might help predict treatment outcomes and provide a new target for molecular therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical presentation prognostic factors intrahepatic extrahepatic cholangiocarcinoma tertiary care center background incidence cholangiocarcinoma rising accurate predictors survival diagnosis well defined aim clarify clinical presentation prognostic factors intrahepatic cholangiocarcinoma extrahepatic cholangiocarcinoma contemporary cohort patients methods records consecutive patients university michigan hospital diagnosed cholangiocarcinoma january 2003 april 2008 reviewed results 136 patients cholangiocarcinoma 79 intra 57 extrahepatic cholangiocarcinoma median survival 27 3 months 25 8 months intrahepatic cholangiocarcinoma 30 3 months extrahepatic cholangiocarcinoma independent predictors mortality presentation multivariate analysis elevated bilirubin level hr 1 04 95 ci 1 01 1 07 ca 19 9 levels 100 u ml hr 1 90 95 ci 1 17 3 08 stage disease hr 1 51 95 ci 1 16 1 96 adjusting baseline prognostic factors surgical therapy associated improved survival hr 0 48 95 ci 0 26 0 88 significant differences regarding clinical presentation disease stage p 0 98 survival p 0 51 intra extrahepatic cholangiocarcinoma conclusions survival cholangiocarcinoma remains poor significant difference outcomes intra extrahepatic cholangiocarcinoma stage disease bilirubin level ca 19 9 level important prognostic factors presentation surgical therapy provides similar efficacy tumours adjusted prognostic variables stn","probabilities":0.9799733,"Title":"Clinical Presentation And Prognostic Factors For Intrahepatic And Extrahepatic Cholangiocarcinoma In A Tertiary Care Center","Abstract":"Background: The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined. \r\n\r\n Aim: To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients. \r\n\r\n Methods: Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed. \r\n\r\n Results: In all, 136 patients had cholangiocarcinoma (79 intra- and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months-25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01-1.07), CA 19-9 levels >100 U/mL (HR 1.90, 95%CI 1.17-3.08) and stage of disease (HR 1.51, 95%CI 1.16-1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26-0.88). There were no significant differences regarding clinical presentation, disease stage (P = 0.98), and survival (P = 0.51) between intra- and extrahepatic cholangiocarcinoma. \r\n\r\n Conclusions: Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra- and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19-9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables.","Source":"STN","category":"HUMAN","training_data":"Clinical Presentation And Prognostic Factors For Intrahepatic And Extrahepatic Cholangiocarcinoma In A Tertiary Care Center Background: The incidence of cholangiocarcinoma is rising. Accurate predictors of survival at diagnosis are not well defined. \r\n\r\n Aim: To clarify the clinical presentation and prognostic factors of intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma in a contemporary cohort of patients. \r\n\r\n Methods: Records for consecutive patients at the University of Michigan hospital diagnosed with cholangiocarcinoma between January 2003 and April 2008 were reviewed. \r\n\r\n Results: In all, 136 patients had cholangiocarcinoma (79 intra- and 57 extrahepatic cholangiocarcinoma). Median survival was 27.3 months-25.8 months for intrahepatic cholangiocarcinoma and 30.3 months for extrahepatic cholangiocarcinoma. Independent predictors of mortality at presentation on multivariate analysis were elevated bilirubin level (HR 1.04, 95%CI 1.01-1.07), CA 19-9 levels >100 U/mL (HR 1.90, 95%CI 1.17-3.08) and stage of disease (HR 1.51, 95%CI 1.16-1.96). After adjusting for baseline prognostic factors, surgical therapy was associated with improved survival (HR 0.48; 95% CI 0.26-0.88). There were no significant differences regarding clinical presentation, disease stage (P = 0.98), and survival (P = 0.51) between intra- and extrahepatic cholangiocarcinoma. \r\n\r\n Conclusions: Survival for cholangiocarcinoma remains poor with no significant difference in outcomes between intra- and extrahepatic cholangiocarcinoma. Stage of disease, bilirubin level and CA 19-9 level are important prognostic factors at presentation. Surgical therapy provides similar efficacy for both tumours when adjusted for other prognostic variables. STN","prediction_labels":"HUMAN"},{"cleaned":"fact hep increases accuracy survival prediction hcc patients added ecog performance status background aim eastern cooperative oncology group performance status ecog ps strong predictor survival patients hepatocellular carcinoma hcc used liver function tumour burden barcelona clinic liver cancer bclc staging system work assesses whether health related quality life hrql measured functional assessment cancer therapy hepatobiliary fact hep questionnaire discriminates hcc patients terms survival adds prognostic information ecog ps methods total 242 patients participating prospective bern hcc cohort university hospital bern analysed relationship fact hep sociodemographic clinical factors including survival assessed analysis treatment subgroups performed using kaplan meier curves long rank test additionally ability predict overall survival compared ecog ps fact hep total subscales using nagelkerke pseudo r2 results fact hep subscales significantly worse females patients limited liver function fact hep total subscales except social family well subscale showed significant differences ecog ps groups significant predictors survival ecog ps groups followed functional well subscale best predicting survival resection subgroup significant differences os regarding hrql found adding functional well subscale ecog ps accuracy survival prediction significantly increased conclusion hrql assessed fact hep questionnaire reliable prognostic predictor survival patients hcc adds prognostic information ecog ps stn","probabilities":0.9799733,"Title":"Fact-Hep Increases The Accuracy Of Survival Prediction In Hcc Patients When Added To Ecog Performance Status","Abstract":"Background and aim: The Eastern Cooperative Oncology Group Performance Status (ECOG PS) is a strong predictor of survival for patients with hepatocellular carcinoma (HCC), and is used with liver function and tumour burden in the Barcelona Clinic Liver Cancer (BCLC) staging system. This work assesses whether the health-related quality of life (HRQL), measured by the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire, discriminates HCC patients in terms of survival and adds prognostic information to ECOG PS. \n\n Methods: A total of 242 patients participating in the prospective Bern HCC Cohort at the University Hospital Bern were analysed. The relationship between FACT-Hep and sociodemographic and clinical factors, including survival, were assessed. An analysis on treatment subgroups was performed using Kaplan-Meier curves and Long-Rank test. Additionally, the ability to predict overall survival was compared between the ECOG PS and FACT-Hep total and subscales using Nagelkerke pseudo-R2 . \n\n Results: FACT-Hep subscales were significantly worse in females and in patients with limited liver function. FACT-Hep total and all subscales, except the social/family well-being subscale showed significant differences between ECOG PS groups and were significant predictors of survival. ECOG PS groups, followed by the functional well-being subscale, were the best at predicting survival. In the resection subgroup, significant differences in OS regarding to HRQL were found. When adding the functional well-being subscale to ECOG PS, the accuracy of the survival prediction was significantly increased. \n\n Conclusion: HRQL assessed by the FACT-Hep questionnaire is a reliable prognostic predictor of survival for patients with HCC and it adds prognostic information to the ECOG PS.","Source":"STN","category":"HUMAN","training_data":"Fact-Hep Increases The Accuracy Of Survival Prediction In Hcc Patients When Added To Ecog Performance Status Background and aim: The Eastern Cooperative Oncology Group Performance Status (ECOG PS) is a strong predictor of survival for patients with hepatocellular carcinoma (HCC), and is used with liver function and tumour burden in the Barcelona Clinic Liver Cancer (BCLC) staging system. This work assesses whether the health-related quality of life (HRQL), measured by the Functional Assessment of Cancer Therapy-Hepatobiliary (FACT-Hep) questionnaire, discriminates HCC patients in terms of survival and adds prognostic information to ECOG PS. \n\n Methods: A total of 242 patients participating in the prospective Bern HCC Cohort at the University Hospital Bern were analysed. The relationship between FACT-Hep and sociodemographic and clinical factors, including survival, were assessed. An analysis on treatment subgroups was performed using Kaplan-Meier curves and Long-Rank test. Additionally, the ability to predict overall survival was compared between the ECOG PS and FACT-Hep total and subscales using Nagelkerke pseudo-R2 . \n\n Results: FACT-Hep subscales were significantly worse in females and in patients with limited liver function. FACT-Hep total and all subscales, except the social/family well-being subscale showed significant differences between ECOG PS groups and were significant predictors of survival. ECOG PS groups, followed by the functional well-being subscale, were the best at predicting survival. In the resection subgroup, significant differences in OS regarding to HRQL were found. When adding the functional well-being subscale to ECOG PS, the accuracy of the survival prediction was significantly increased. \n\n Conclusion: HRQL assessed by the FACT-Hep questionnaire is a reliable prognostic predictor of survival for patients with HCC and it adds prognostic information to the ECOG PS. STN","prediction_labels":"HUMAN"},{"cleaned":"cdk10 functions tumor suppressor gene regulates survivability biliary tract cancer cells cyclin dependent kinase 10 cdk10 member cdc2 family kinases demonstrated important determinant resistance endocrine therapy breast cancer investigate expression possible function cdk10 biliary tract cancer btc systematically examined cdk10 tissues cell lines found expression cdk10 downregulated biliary tract tumors cell lines remarkably expression cdk10 correlated clinical characteristics overexpression knockdown cdk10 respectively inhibited promoted cell proliferation colony formation migration suggests cdk10 functions tumor suppressor gene btc overexpression cdk10 caused malignant cells become sensitive chemotherapy hostile environments suggesting cdk10 functions regulate survivability btc cells investigated expression six genes resolve mechanism c raf negatively regulated cdk10 cells specimens results indicate cdk10 plays crucial role growth survivability biliary tract cancer offers potential therapeutic target fatal disease pubmed","probabilities":0.875,"Title":"CDK10 functions as a tumor suppressor gene and regulates survivability of biliary tract cancer cells","Abstract":"Cyclin-dependent kinase 10 (CDK10) is a member of the Cdc2 family of kinases, and has been demonstrated to be an important determinant of resistance to endocrine therapy for breast cancer. To investigate the expression and possible function of CDK10 in biliary tract cancer (BTC), we systematically examined CDK10 in tissues and cell lines. We found that expression of CDK10 was downregulated in both biliary tract tumors and cell lines. Remarkably, the expression of CDK10 correlated with clinical characteristics. Overexpression or knockdown of CDK10, respectively, inhibited or promoted cell proliferation, colony formation and migration. This suggests that CDK10 functions as a tumor suppressor gene in BTC. Overexpression of CDK10 caused malignant cells to become sensitive to chemotherapy and other hostile environments, suggesting that CDK10 functions to regulate survivability of BTC cells. We investigated the expression of six genes to resolve the mechanism. c-RAF was negatively regulated by CDK10 in both cells and specimens. Our results indicate that CDK10 plays a crucial role in the growth and survivability of biliary tract cancer, and offers a potential therapeutic target for this fatal disease.","Source":"PubMed","category":"ANIMAL","training_data":"CDK10 functions as a tumor suppressor gene and regulates survivability of biliary tract cancer cells Cyclin-dependent kinase 10 (CDK10) is a member of the Cdc2 family of kinases, and has been demonstrated to be an important determinant of resistance to endocrine therapy for breast cancer. To investigate the expression and possible function of CDK10 in biliary tract cancer (BTC), we systematically examined CDK10 in tissues and cell lines. We found that expression of CDK10 was downregulated in both biliary tract tumors and cell lines. Remarkably, the expression of CDK10 correlated with clinical characteristics. Overexpression or knockdown of CDK10, respectively, inhibited or promoted cell proliferation, colony formation and migration. This suggests that CDK10 functions as a tumor suppressor gene in BTC. Overexpression of CDK10 caused malignant cells to become sensitive to chemotherapy and other hostile environments, suggesting that CDK10 functions to regulate survivability of BTC cells. We investigated the expression of six genes to resolve the mechanism. c-RAF was negatively regulated by CDK10 in both cells and specimens. Our results indicate that CDK10 plays a crucial role in the growth and survivability of biliary tract cancer, and offers a potential therapeutic target for this fatal disease. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"low vdac1 expression associated aggressive phenotype reduced overall patient survival cholangiocellular carcinoma abstract cancer cells frequently exhibit dysfunctional oxidative phosphorylation oxphos concomitant increase glycolytic flux investigated expression oxphos complex subunits mitochondrial mass 34 human cholangiocellular carcinomas cccs adjacent normal tissue using tissue microarrays tumor periphery oxphos complexes reduced except complex addition significantly lower levels complex iv found tumor center p 0 0001 mitochondrial mass indicated vdac1 expression significantly increased cccs compared corresponding normal tissue p 0 0001 vdac1 levels inversely correlated uicc union internationale contre le cancer cancer stage classification p 0 0065 furthermore significantly lower vdac1 present patients lymph node involvement p 0 02 consistent patients whose carcinomas expressed vdac1 low moderate levels significantly reduced survival compared high expressors p 0 05 therefore low mitochondrial mass associated aggressive ccc metabolic features indicative warburg phenotype cccs metabolic signature potential therapeutic implications tumors low mitochondrial function may targeted metabolic therapies high fat low carbohydrate ketogenic diet stn","probabilities":1.0,"Title":"Low Vdac1 Expression Is Associated With An Aggressive Phenotype And Reduced Overall Patient Survival In Cholangiocellular Carcinoma","Abstract":"Abstract: Cancer cells frequently exhibit dysfunctional oxidative phosphorylation (OXPHOS) and a concomitant increase in glycolytic flux. We investigated the expression of OXPHOS complex subunits and mitochondrial mass in 34 human cholangiocellular carcinomas (CCCs) and adjacent normal tissue by using tissue microarrays. In the tumor periphery, all OXPHOS complexes were reduced except complex I. In addition, significantly lower levels of complex IV were found at the tumor center (p < 0.0001). Mitochondrial mass, as indicated by VDAC1 expression, was significantly increased in CCCs compared to corresponding normal tissue (p < 0.0001). VDAC1 levels were inversely correlated with UICC (Union Internationale Contre le Cancer) cancer stage classification (p = 0.0065). Furthermore, significantly lower VDAC1 was present in patients with lymph node involvement (p = 0.02). Consistent with this, patients whose carcinomas expressed VDAC1 at low to moderate levels had significantly reduced survival compared to high expressors (p < 0.05). Therefore, low mitochondrial mass is associated with more aggressive CCC. These metabolic features are indicative of a Warburg phenotype in CCCs. This metabolic signature has potential therapeutic implications because tumors with low mitochondrial function may be targeted by metabolic therapies such as a high-fat, low-carbohydrate ketogenic diet.","Source":"STN","category":"ANIMAL","training_data":"Low Vdac1 Expression Is Associated With An Aggressive Phenotype And Reduced Overall Patient Survival In Cholangiocellular Carcinoma Abstract: Cancer cells frequently exhibit dysfunctional oxidative phosphorylation (OXPHOS) and a concomitant increase in glycolytic flux. We investigated the expression of OXPHOS complex subunits and mitochondrial mass in 34 human cholangiocellular carcinomas (CCCs) and adjacent normal tissue by using tissue microarrays. In the tumor periphery, all OXPHOS complexes were reduced except complex I. In addition, significantly lower levels of complex IV were found at the tumor center (p < 0.0001). Mitochondrial mass, as indicated by VDAC1 expression, was significantly increased in CCCs compared to corresponding normal tissue (p < 0.0001). VDAC1 levels were inversely correlated with UICC (Union Internationale Contre le Cancer) cancer stage classification (p = 0.0065). Furthermore, significantly lower VDAC1 was present in patients with lymph node involvement (p = 0.02). Consistent with this, patients whose carcinomas expressed VDAC1 at low to moderate levels had significantly reduced survival compared to high expressors (p < 0.05). Therefore, low mitochondrial mass is associated with more aggressive CCC. These metabolic features are indicative of a Warburg phenotype in CCCs. This metabolic signature has potential therapeutic implications because tumors with low mitochondrial function may be targeted by metabolic therapies such as a high-fat, low-carbohydrate ketogenic diet. STN","prediction_labels":"ANIMAL"},{"cleaned":"comparison thinprep urocyte cytospin slide preparations gastrointestinal specimens evaluation retrospective performance review gastrointestinal gi tract cytology high specificity poor sensitivity detecting gi tract cancer newer methods slide preparation may improve cytology performance additionally permit molecular slide based assays improve diagnostic accuracy split sample validation study compared slides prepared using thinprep urocyte filters cytocentrifuge method respect cellularity stain quality interpretation 15 slide split sample study urocyte slide preparations judged superior cytocentrifuge preparations method implemented gi cytology december 2006 assess diagnostic performance gi cytology retrospectively reviewed outcomes one year implementation urocyte filter slide preparation sensitivity specificity positive predictive value negative predictive value slide preparations largely equivalent one another compared favorably values literature varied greatly depending atypical suspicious atypical cases defined calculations biopsied biliary samples highest sensitivities observed atypical suspicious atypical cases considered positive malignancy lower suspicious atypical cases considered positive atypical cases considered negative malignancy highlights difficulty comparing studies define atypical classes differently points need well defined approach performance evaluation relates directly diagnostic information used clinically conclude urocyte filter slide preparation valid evaluation gi cytology specimens may simplify adjunct molecular testing fish first reported use urocyte filters preparation gi specimens pubmed","probabilities":0.5555556,"Title":"Comparison of ThinPrep UroCyte and cytospin slide preparations for gastrointestinal specimens: evaluation and retrospective performance review","Abstract":"Gastrointestinal (GI) tract cytology has high specificity but poor sensitivity for detecting GI tract cancer. Newer methods of slide preparation may improve cytology performance and additionally permit molecular slide-based assays that could improve diagnostic accuracy. A split-sample validation study compared slides prepared using ThinPrep UroCyte filters or a cytocentrifuge method with respect to cellularity, stain quality, and interpretation. In this 15-slide split-sample study, UroCyte slide preparations were judged to be superior to cytocentrifuge preparations, and the method was implemented for GI cytology in December 2006. To assess diagnostic performance for GI cytology, we retrospectively reviewed outcomes for one year before and after implementation of UroCyte filter slide preparation. Sensitivity, specificity, positive predictive value, and negative predictive value for both slide preparations were largely equivalent to one another and compared favorably with values in the literature, but varied greatly depending on how atypical and suspicious-atypical cases were defined for calculations. For biopsied biliary samples, the highest sensitivities were observed when all atypical and suspicious-atypical cases were considered positive for malignancy, but were lower when suspicious-atypical cases were considered positive and atypical cases were considered negative for malignancy. This highlights the difficulty with comparing studies that define atypical classes differently, and points to the need for a well-defined approach to performance evaluation that relates directly to how diagnostic information is used clinically. We conclude that the UroCyte filter slide preparation is valid for evaluation of GI cytology specimens and may simplify adjunct molecular testing such as FISH. This is the first reported use of UroCyte filters for preparation of GI specimens.","Source":"PubMed","category":"ANIMAL","training_data":"Comparison of ThinPrep UroCyte and cytospin slide preparations for gastrointestinal specimens: evaluation and retrospective performance review Gastrointestinal (GI) tract cytology has high specificity but poor sensitivity for detecting GI tract cancer. Newer methods of slide preparation may improve cytology performance and additionally permit molecular slide-based assays that could improve diagnostic accuracy. A split-sample validation study compared slides prepared using ThinPrep UroCyte filters or a cytocentrifuge method with respect to cellularity, stain quality, and interpretation. In this 15-slide split-sample study, UroCyte slide preparations were judged to be superior to cytocentrifuge preparations, and the method was implemented for GI cytology in December 2006. To assess diagnostic performance for GI cytology, we retrospectively reviewed outcomes for one year before and after implementation of UroCyte filter slide preparation. Sensitivity, specificity, positive predictive value, and negative predictive value for both slide preparations were largely equivalent to one another and compared favorably with values in the literature, but varied greatly depending on how atypical and suspicious-atypical cases were defined for calculations. For biopsied biliary samples, the highest sensitivities were observed when all atypical and suspicious-atypical cases were considered positive for malignancy, but were lower when suspicious-atypical cases were considered positive and atypical cases were considered negative for malignancy. This highlights the difficulty with comparing studies that define atypical classes differently, and points to the need for a well-defined approach to performance evaluation that relates directly to how diagnostic information is used clinically. We conclude that the UroCyte filter slide preparation is valid for evaluation of GI cytology specimens and may simplify adjunct molecular testing such as FISH. This is the first reported use of UroCyte filters for preparation of GI specimens. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"bactibilia diseases biliary tract pancreatic gland patients older 80 years strobe retrospective cohort study teaching hospital italy bile lipid rich sterile solution produced liver infected resulting bactibilia higher incidence postoperative infectious complications seen patients bactibilia recently gram negative bacteria linked tumor associated inflammatory status study retrospective cohort study 39 patients 80 years age 53 85 males 46 15 females hospitalized diseases biliopancreatic system one teaching hospital italy january 2011 december 2012 follow 5 years common biliary diseases surgery pancreatic head cancer p 0 0001 gallbladder cancer p 0 0051 common bacteria bile e coli p 0 0180 pseudomonas spp p 0 0001 uni multivariate linear correlation analysis revealed patients pancreatic head cancer low survival times compared patients diseases moreover bacterium type positive predictor survival time compared variables data confirm e coli pathogen patients gallbladder pancreatic cancer although influence bactibilia developing surgical complications limited consider composition crucial properly address antibiotic treatment biliary tract infections especially elderly pubmed","probabilities":0.9799733,"Title":"Bactibilia in diseases of the biliary tract and pancreatic gland in patients older than 80 years: a STROBE-retrospective cohort study in a teaching hospital in Italy","Abstract":"Bile is a lipid-rich sterile solution produced in the liver that can be infected resulting in bactibilia. A higher incidence of postoperative infectious complications has been seen in patients with bactibilia. Recently, gram-negative bacteria have been linked to a tumor-associated inflammatory status. This study is a retrospective cohort study of 39 patients, who are over 80 years of age only (53.85% males and 46.15% females), hospitalized with diseases of the biliopancreatic system in one teaching hospital in Italy from January 2011 to December 2012 with a follow-up of 5 years. The most common biliary diseases after surgery were pancreatic head cancer (p < 0.0001) and gallbladder cancer (p = 0.0051), while the most common bacteria in the bile were E. coli (p = 0.0180) and Pseudomonas spp. (p < 0.0001). Uni- and multivariate linear correlation analysis revealed that patients with pancreatic head cancer had low survival times compared to patients with other diseases. Moreover, the bacterium type was a positive predictor of survival time compared to other variables. Our data confirm E. coli as a pathogen in patients with gallbladder and pancreatic cancer. Although the influence of bactibilia in developing surgical complications is limited, we consider that its composition is crucial to properly address the antibiotic treatment in biliary tract infections, especially in the elderly.","Source":"PubMed","category":"HUMAN","training_data":"Bactibilia in diseases of the biliary tract and pancreatic gland in patients older than 80 years: a STROBE-retrospective cohort study in a teaching hospital in Italy Bile is a lipid-rich sterile solution produced in the liver that can be infected resulting in bactibilia. A higher incidence of postoperative infectious complications has been seen in patients with bactibilia. Recently, gram-negative bacteria have been linked to a tumor-associated inflammatory status. This study is a retrospective cohort study of 39 patients, who are over 80 years of age only (53.85% males and 46.15% females), hospitalized with diseases of the biliopancreatic system in one teaching hospital in Italy from January 2011 to December 2012 with a follow-up of 5 years. The most common biliary diseases after surgery were pancreatic head cancer (p < 0.0001) and gallbladder cancer (p = 0.0051), while the most common bacteria in the bile were E. coli (p = 0.0180) and Pseudomonas spp. (p < 0.0001). Uni- and multivariate linear correlation analysis revealed that patients with pancreatic head cancer had low survival times compared to patients with other diseases. Moreover, the bacterium type was a positive predictor of survival time compared to other variables. Our data confirm E. coli as a pathogen in patients with gallbladder and pancreatic cancer. Although the influence of bactibilia in developing surgical complications is limited, we consider that its composition is crucial to properly address the antibiotic treatment in biliary tract infections, especially in the elderly. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical outcomes 230 resected hilar cholangiocarcinoma single centre background low resectability rate poor survival outcomes surgical resection hilar cholangiocarcinoma common institutions retrospectively reviewed surgical outcomes hilar cholangiocarcinoma tertiary institution focusing surgical procedures radicalities survival rates independent prognostic factors methods two hundred thirty patients underwent surgical resection hilar cholangiocarcinoma 1995 2010 retrospectively analysed based clinical variables bismuth corlette types radicality operation survival rates results median overall disease free survival time whole cohort 39 1 19 2 months respectively patients type ii tumour likely undergo segmental bile duct resection combined liver resection lower r0 rates 68 2 76 1 respectively liver resection p 0 001 combined caudate lobectomy p 0 003 associated significantly higher r0 rates multivariate analysis showed lymph node metastasis p 0 001 preoperative level bilirubin 3 0 mg dl p 0 003 positive resection margin p 0 033 independent prognostic factors overall survival conclusion liver resection combined caudate lobectomy increased curative resection rates hilar cholangiocarcinoma regardless bismuth corlette types preoperative biliary drainage performed jaundiced patients improve perioperative outcome survival pubmed","probabilities":0.9799733,"Title":"Surgical outcomes of 230 resected hilar cholangiocarcinoma in a single centre","Abstract":"BACKGROUND: Low resectability rate and poor survival outcomes after surgical resection for hilar cholangiocarcinoma are common in most institutions. We retrospectively reviewed the surgical outcomes of hilar cholangiocarcinoma in a tertiary institution focusing on the surgical procedures, radicalities, survival rates and independent prognostic factors. METHODS: Two hundred thirty patients who underwent surgical resection for hilar cholangiocarcinoma between 1995 and 2010 were retrospectively analysed based on the clinical variables, Bismuth-Corlette types, radicality of operation and survival rates. RESULTS: The median overall and disease-free survival time in the whole cohort were 39.1 and 19.2 months, respectively. Patients with type I or II tumour were more likely to undergo segmental bile duct resection than combined liver resection with lower R0 rates (68.2% and 76.1%, respectively). Liver resection (P < 0.001) and combined caudate lobectomy (P = 0.003) were associated with significantly higher R0 rates. Multivariate analysis showed that lymph node metastasis (P = 0.001), preoperative level of bilirubin above 3.0 mg/dL (P = 0.003) and positive resection margin (P = 0.033) were independent prognostic factors on overall survival. CONCLUSION: Liver resection and combined caudate lobectomy increased curative resection rates in hilar cholangiocarcinoma regardless of Bismuth-Corlette types. Preoperative biliary drainage should be performed in jaundiced patients to improve perioperative outcome and survival.","Source":"PubMed","category":"HUMAN","training_data":"Surgical outcomes of 230 resected hilar cholangiocarcinoma in a single centre BACKGROUND: Low resectability rate and poor survival outcomes after surgical resection for hilar cholangiocarcinoma are common in most institutions. We retrospectively reviewed the surgical outcomes of hilar cholangiocarcinoma in a tertiary institution focusing on the surgical procedures, radicalities, survival rates and independent prognostic factors. METHODS: Two hundred thirty patients who underwent surgical resection for hilar cholangiocarcinoma between 1995 and 2010 were retrospectively analysed based on the clinical variables, Bismuth-Corlette types, radicality of operation and survival rates. RESULTS: The median overall and disease-free survival time in the whole cohort were 39.1 and 19.2 months, respectively. Patients with type I or II tumour were more likely to undergo segmental bile duct resection than combined liver resection with lower R0 rates (68.2% and 76.1%, respectively). Liver resection (P < 0.001) and combined caudate lobectomy (P = 0.003) were associated with significantly higher R0 rates. Multivariate analysis showed that lymph node metastasis (P = 0.001), preoperative level of bilirubin above 3.0 mg/dL (P = 0.003) and positive resection margin (P = 0.033) were independent prognostic factors on overall survival. CONCLUSION: Liver resection and combined caudate lobectomy increased curative resection rates in hilar cholangiocarcinoma regardless of Bismuth-Corlette types. Preoperative biliary drainage should be performed in jaundiced patients to improve perioperative outcome and survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radioembolization improves survival intrahepatic cholangiocarcinoma seer medicare population study purpose analyze cost effectiveness radioembolization treatment intrahepatic cholangiocarcinoma icc using surveillance epidemiology end results seer medicare cancer database materials methods cost measured total treatment related reimbursement patients diagnosed icc received chemotherapy alone chemotherapy yttrium 90 radioembolization assessed seer medicare cancer database 1999 2012 survival analysis performed incremental cost effectiveness ratios generated results study included 585 patients average age diagnosis 71 years standard deviation 9 9 52 patients male twelve percent patients received chemotherapy radioembolization n 72 88 patients n 513 received chemotherapy median survival 1043 days 95 confidence interval ci 894 1244 chemotherapy plus radioembolization 811 days 95 ci 705 925 chemotherapy alone p 02 patients received combination therapy slightly younger 71 vs 69 years p 03 significant differences observed treatment groups age treatment sex race city size multivariable analysis showed hazard ratio progression combination therapy versus chemotherapy alone 0 76 95 ci 0 59 0 97 p 029 incremental cost effectiveness ratio measure cost added year life 50 058 65 per year quartiles 11 454 63 52 763 28 conclusions combination therapy icc chemotherapy radioembolization associated higher median survival cost effective treatment median cost 50 058 65 per additional year survival stn","probabilities":0.9799733,"Title":"Radioembolization Improves Survival In Intrahepatic Cholangiocarcinoma: A Seer-Medicare Population Study","Abstract":"Purpose: To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database. \r\n\r\n Materials and methods: Cost as measured by total treatment-related reimbursement in patients diagnosed with ICC who received chemotherapy alone or chemotherapy and yttrium-90 radioembolization was assessed in the SEER Medicare cancer database (1999-2012). Survival analysis was performed, and incremental cost-effectiveness ratios were generated. \r\n\r\n Results: The study included 585 patients. Average age at diagnosis was 71 years (standard deviation: 9.9), and 52% of patients were male. Twelve percent of patients received chemotherapy with radioembolization (n = 72), and 88% of patients (n = 513) received only chemotherapy. Median survival was 1043 days (95% confidence interval [CI]: 894-1244) for chemotherapy plus radioembolization and 811 days (95% CI: 705-925) for chemotherapy alone (P = .02). Patients who received combination therapy were slightly younger (71 vs 69 years, P = .03). No significant differences were observed between treatment groups in age at treatment, sex, race, or city size. Multivariable analysis showed a hazard ratio for progression for combination therapy versus chemotherapy alone of 0.76 (95% CI: 0.59-0.97, P = .029). The incremental cost-effectiveness ratio, a measure of cost of each added year of life, was $50,058.65 per year (quartiles: $11,454.63, $52,763.28). \r\n\r\n Conclusions: Combination therapy of ICC with chemotherapy and radioembolization is associated with higher median survival and can be a cost-effective treatment, with a median cost of $50,058.65 per additional year of survival.","Source":"STN","category":"HUMAN","training_data":"Radioembolization Improves Survival In Intrahepatic Cholangiocarcinoma: A Seer-Medicare Population Study Purpose: To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database. \r\n\r\n Materials and methods: Cost as measured by total treatment-related reimbursement in patients diagnosed with ICC who received chemotherapy alone or chemotherapy and yttrium-90 radioembolization was assessed in the SEER Medicare cancer database (1999-2012). Survival analysis was performed, and incremental cost-effectiveness ratios were generated. \r\n\r\n Results: The study included 585 patients. Average age at diagnosis was 71 years (standard deviation: 9.9), and 52% of patients were male. Twelve percent of patients received chemotherapy with radioembolization (n = 72), and 88% of patients (n = 513) received only chemotherapy. Median survival was 1043 days (95% confidence interval [CI]: 894-1244) for chemotherapy plus radioembolization and 811 days (95% CI: 705-925) for chemotherapy alone (P = .02). Patients who received combination therapy were slightly younger (71 vs 69 years, P = .03). No significant differences were observed between treatment groups in age at treatment, sex, race, or city size. Multivariable analysis showed a hazard ratio for progression for combination therapy versus chemotherapy alone of 0.76 (95% CI: 0.59-0.97, P = .029). The incremental cost-effectiveness ratio, a measure of cost of each added year of life, was $50,058.65 per year (quartiles: $11,454.63, $52,763.28). \r\n\r\n Conclusions: Combination therapy of ICC with chemotherapy and radioembolization is associated with higher median survival and can be a cost-effective treatment, with a median cost of $50,058.65 per additional year of survival. STN","prediction_labels":"HUMAN"},{"cleaned":"influence factors recurrence curative resection ampulla vater cancer background consideration ampullary adenocarcinoma stage lymph node metastases perineural invasion tumor differentiation pancraticobiliary type lymph node ratio considered prognostic factors objectives study investigate surgical outcomes clinicopathological predictors affecting survival recurrence examine prognostic roles histopathological subtype immunohistochemical markers methods april 2006 september 2012 37 patients underwent curative resection ampullar vater adenocarcinoma enrolled study retrospective review performed based medical records immunohistochemical expression histopathological type clinicopathologic factors analyzed results 5 year overall survival rates disease free survival rates surgery 77 4 75 7 respectively multivariate cox regression analysis showed advanced stage p 0 019 positive expression cytokeratin 7 ck7 negative expression cytokeratin 20 ck20 p 0 046 identified significant independent factors related survival poor differentiation p 0 031 significantly influenced disease free survival multivariate analysis conclusions advanced stage significant prognostic factor affecting survival ampullary adenocarcinoma also positive expression ck7 negative expression ck20 independent factor related overall survival stn","probabilities":0.9799733,"Title":"The Influence Of Factors On Recurrence After Curative Resection For Ampulla Of Vater Cancer","Abstract":"Background: In the consideration of ampullary adenocarcinoma, T stage, lymph node metastases, perineural invasion, tumor differentiation, pancraticobiliary type, and lymph node ratio are considered prognostic factors. The objectives of this study were to investigate surgical outcomes and the clinicopathological predictors affecting survival and recurrence, and to examine the prognostic roles of histopathological subtype and immunohistochemical markers. \r\n\r\n Methods: From April 2006 to September 2012, 37 patients who underwent curative resection of ampullar of Vater adenocarcinoma were enrolled in this study. A retrospective review was performed based on medical records. Immunohistochemical expression, histopathological type and clinicopathologic factors were analyzed. \r\n\r\n Results: The 5-year overall survival rates and disease-free survival rates after surgery were 77.4 and 75.7 %, respectively. Multivariate Cox regression analysis showed that advanced T stage (p = 0.019) and positive expression of Cytokeratin 7 (CK7) with negative expression of Cytokeratin 20 (CK20) (p = 0.046) were identified as significant independent factors related to survival, and poor differentiation (p = 0.031) significantly influenced disease-free survival in multivariate analysis. \r\n\r\n Conclusions: Advanced T stage is a significant prognostic factor affecting survival in ampullary adenocarcinoma. Also, positive expression of CK7 with negative expression of CK20 is an independent factor related to overall survival.","Source":"STN","category":"HUMAN","training_data":"The Influence Of Factors On Recurrence After Curative Resection For Ampulla Of Vater Cancer Background: In the consideration of ampullary adenocarcinoma, T stage, lymph node metastases, perineural invasion, tumor differentiation, pancraticobiliary type, and lymph node ratio are considered prognostic factors. The objectives of this study were to investigate surgical outcomes and the clinicopathological predictors affecting survival and recurrence, and to examine the prognostic roles of histopathological subtype and immunohistochemical markers. \r\n\r\n Methods: From April 2006 to September 2012, 37 patients who underwent curative resection of ampullar of Vater adenocarcinoma were enrolled in this study. A retrospective review was performed based on medical records. Immunohistochemical expression, histopathological type and clinicopathologic factors were analyzed. \r\n\r\n Results: The 5-year overall survival rates and disease-free survival rates after surgery were 77.4 and 75.7 %, respectively. Multivariate Cox regression analysis showed that advanced T stage (p = 0.019) and positive expression of Cytokeratin 7 (CK7) with negative expression of Cytokeratin 20 (CK20) (p = 0.046) were identified as significant independent factors related to survival, and poor differentiation (p = 0.031) significantly influenced disease-free survival in multivariate analysis. \r\n\r\n Conclusions: Advanced T stage is a significant prognostic factor affecting survival in ampullary adenocarcinoma. Also, positive expression of CK7 with negative expression of CK20 is an independent factor related to overall survival. STN","prediction_labels":"HUMAN"},{"cleaned":"hepatic arterial infusion biliary tract carcinoma single center experience aim aim present study evaluate single center experience hepatic arterial infusion hai patients biliary tract carcinomas patients methods retrospective analysis 60 patients treated 1997 2011 performed results patients treated hai combination 5 fluorouracil folinic acid cisplatin response evaluable patients predominantly prior surgical procedures median survival patients 15 1 months 5 year survival 13 survival significantly better patients treated radical surgery median 50 1 months 5 year survival 45 palliative surgery median 22 5 months 5 year survival 13 compared surgery median 7 6 months 5 year survival 3 conclusion current data demonstrate efficacy hai patients biliary tract carcinoma hai therapeutic method considered patients inoperable biliary tract carcinoma extrahepatic spread pubmed","probabilities":0.9799733,"Title":"Hepatic arterial infusion for biliary tract carcinoma: single-center experience","Abstract":"AIM: The aim of the present study was to evaluate a single-center experience in hepatic arterial infusion (HAI) of patients with biliary tract carcinomas. PATIENTS AND METHODS: A retrospective analysis of 60 patients treated between 1997 and 2011 was performed. RESULTS: Most patients were treated with HAI of a combination of 5-fluorouracil, folinic acid and cisplatin. The response was not evaluable in most patients, predominantly because of prior surgical procedures. The median survival of all patients was 15.1 months (5-year survival=13%). The survival was significantly better in patients treated with radical surgery (median=50.1 months, 5-year survival=45%) or palliative surgery (median=22.5 months, 5-year survival=13%) compared to no surgery (median=7.6 months, 5-year survival=3%). CONCLUSION: The current data demonstrate the efficacy of HAI in patients with biliary tract carcinoma. HAI is a therapeutic method to be considered in patients with inoperable biliary tract carcinoma and no extrahepatic spread.","Source":"PubMed","category":"HUMAN","training_data":"Hepatic arterial infusion for biliary tract carcinoma: single-center experience AIM: The aim of the present study was to evaluate a single-center experience in hepatic arterial infusion (HAI) of patients with biliary tract carcinomas. PATIENTS AND METHODS: A retrospective analysis of 60 patients treated between 1997 and 2011 was performed. RESULTS: Most patients were treated with HAI of a combination of 5-fluorouracil, folinic acid and cisplatin. The response was not evaluable in most patients, predominantly because of prior surgical procedures. The median survival of all patients was 15.1 months (5-year survival=13%). The survival was significantly better in patients treated with radical surgery (median=50.1 months, 5-year survival=45%) or palliative surgery (median=22.5 months, 5-year survival=13%) compared to no surgery (median=7.6 months, 5-year survival=3%). CONCLUSION: The current data demonstrate the efficacy of HAI in patients with biliary tract carcinoma. HAI is a therapeutic method to be considered in patients with inoperable biliary tract carcinoma and no extrahepatic spread. PubMed","prediction_labels":"HUMAN"},{"cleaned":"circulating biomarkers cholangiocarcinoma background cholangiocarcinoma cca represents second common primary liver malignancy incidence rate constantly increased last decades cca patients face dismal prognosis 5 year survival rate less 5 advanced stage disease surgical tumor resection remained potentially curative treatment option daily practice often feasible due advanced disease stage initial diagnosis summary early detection cholangiocarcinoma essential provide patients potentially curative treatment furthermore prognostic biomarkers represent valuable tool offer patients tailored therapeutic approach accordance life expectancy clinically established biomarker carbohydrate antigen 19 9 shows limited diagnostic prognostic power encouraging evaluation novel biomarkers cholangiocarcinoma last years key massage review assess currently available potential future biomarkers diagnosis prognosis cholangicarcinoma pubmed","probabilities":0.9799733,"Title":"Circulating Biomarkers for Cholangiocarcinoma","Abstract":"BACKGROUND: Cholangiocarcinoma (CCA) represents the second most common primary liver malignancy. The incidence rate has constantly increased over the last decades and CCA patients face a dismal prognosis with a 5-year survival rate of less than 5% for advanced stage of disease. Surgical tumor resection has remained the only potentially curative treatment option in daily practice but is often not feasible due to advanced disease stage at initial diagnosis. SUMMARY: The early detection of cholangiocarcinoma is essential to provide patients with a potentially curative treatment. Furthermore, prognostic biomarkers represent a valuable tool to offer patients a tailored therapeutic approach in accordance to their life expectancy. The clinically most established biomarker carbohydrate antigen 19-9 shows only a limited diagnostic and prognostic power, encouraging the evaluation of novel biomarkers for cholangiocarcinoma in the last years. Key Massage: In this review, we assess currently available and potential future biomarkers for the diagnosis and prognosis of cholangicarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Circulating Biomarkers for Cholangiocarcinoma BACKGROUND: Cholangiocarcinoma (CCA) represents the second most common primary liver malignancy. The incidence rate has constantly increased over the last decades and CCA patients face a dismal prognosis with a 5-year survival rate of less than 5% for advanced stage of disease. Surgical tumor resection has remained the only potentially curative treatment option in daily practice but is often not feasible due to advanced disease stage at initial diagnosis. SUMMARY: The early detection of cholangiocarcinoma is essential to provide patients with a potentially curative treatment. Furthermore, prognostic biomarkers represent a valuable tool to offer patients a tailored therapeutic approach in accordance to their life expectancy. The clinically most established biomarker carbohydrate antigen 19-9 shows only a limited diagnostic and prognostic power, encouraging the evaluation of novel biomarkers for cholangiocarcinoma in the last years. Key Massage: In this review, we assess currently available and potential future biomarkers for the diagnosis and prognosis of cholangicarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"usefulness serum microrna predictive marker recurrence prognosis biliary tract cancer radical surgery biliary tract cancer btc aggressive type malignant tumour even radical resection risk recurrence still high resulting poor prognosis investigated usefulness serum mirnas predictive markers recurrence prognosis patients btc radical surgery using 66 serum samples collected three time points 22 patients btc underwent radical surgery using microarray analysis successfully identified six specific mirnas mir 1225 3p mir 1234 3p mir1260b mir 1470 mir 6834 3p mir 6875 5p associated recurrence prognosis btc radical surgery addition using combination mirnas developed recurrence predictive index predict recurrence patients btc operation high accuracy patients higher index scores cut significantly worse recurrence free survival rfs overall survival os lower index scores cut furthermore index independent factor related rfs os univariate multivariate analyses using cox hazard proportional model overall results provided compelling evidence potential usefulness specific serum mirnas effective predictive tools recurrence prognosis patients btc underwent radical surgery stn","probabilities":0.9799733,"Title":"Usefulness Of Serum Microrna As A Predictive Marker Of Recurrence And Prognosis In Biliary Tract Cancer After Radical Surgery","Abstract":"Biliary tract cancer (BTC) is an aggressive type of malignant tumour. Even after radical resection, the risk of recurrence is still high, resulting in a poor prognosis. Here, we investigated the usefulness of serum miRNAs as predictive markers of recurrence and prognosis for patients with BTC after radical surgery using 66 serum samples that were collected at three time points from 22 patients with BTC who underwent radical surgery. Using microarray analysis, we successfully identified six specific miRNAs (miR-1225-3p, miR-1234-3p, miR1260b, miR-1470, miR-6834-3p, and miR-6875-5p) associated with recurrence and prognosis of BTC after radical surgery. In addition, using a combination of these miRNAs, we developed a recurrence predictive index to predict recurrence in patients with BTC after operation with high accuracy. Patients having higher index scores (≥ cut-off) had significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with lower index scores (<cut-off). Furthermore, the index was an independent factor related to RFS and OS by univariate and multivariate analyses using a Cox hazard proportional model. Overall, our results provided compelling evidence for the potential usefulness of specific serum miRNAs as effective predictive tools for recurrence and prognosis in patients with BTC who underwent radical surgery.","Source":"STN","category":"HUMAN","training_data":"Usefulness Of Serum Microrna As A Predictive Marker Of Recurrence And Prognosis In Biliary Tract Cancer After Radical Surgery Biliary tract cancer (BTC) is an aggressive type of malignant tumour. Even after radical resection, the risk of recurrence is still high, resulting in a poor prognosis. Here, we investigated the usefulness of serum miRNAs as predictive markers of recurrence and prognosis for patients with BTC after radical surgery using 66 serum samples that were collected at three time points from 22 patients with BTC who underwent radical surgery. Using microarray analysis, we successfully identified six specific miRNAs (miR-1225-3p, miR-1234-3p, miR1260b, miR-1470, miR-6834-3p, and miR-6875-5p) associated with recurrence and prognosis of BTC after radical surgery. In addition, using a combination of these miRNAs, we developed a recurrence predictive index to predict recurrence in patients with BTC after operation with high accuracy. Patients having higher index scores (≥ cut-off) had significantly worse recurrence-free survival (RFS) and overall survival (OS) than those with lower index scores (<cut-off). Furthermore, the index was an independent factor related to RFS and OS by univariate and multivariate analyses using a Cox hazard proportional model. Overall, our results provided compelling evidence for the potential usefulness of specific serum miRNAs as effective predictive tools for recurrence and prognosis in patients with BTC who underwent radical surgery. STN","prediction_labels":"HUMAN"},{"cleaned":"diabetes mellitus risk cancer takayama population based prospective cohort study japan diabetes mellitus dm reported associated increased risk site specific cancers however studies assessed associations dm total site specific cancers japan examined association history dm cancer incidence population based prospective cohort study japan total 14 173 men 16 547 women 35 years old completed self administered baseline questionnaire 1992 followed cancer incidence september 1992 march 2008 baseline 6 3 men 2 9 women history diabetes total 1974 men 1514 women identified newly diagnosed cancer hazard ratios hr 95 confidence intervals ci determined using cox proportional hazards models controlling potential confounders men dm modest risk increase total cancer occurrence compared without dm hr 1 09 95 ci 0 93 1 29 increased risk cancer liver hr 2 18 95 ci 1 27 3 74 bile duct hr 2 17 95 ci 1 01 4 66 larynx hr 3 61 95 ci 1 16 11 2 diabetic men observed women significant increased risk total cancer hr 1 35 95 ci 1 06 1 73 stomach cancer hr 2 15 95 ci 1 30 3 54 observed among diabetic subjects data suggest people dm may increased risk total site specific cancers pubmed","probabilities":0.9799733,"Title":"Diabetes mellitus and risk of cancer in Takayama: a population-based prospective cohort study in Japan","Abstract":"Diabetes mellitus (DM) has been reported to be associated with an increased risk of site-specific cancers; however, few studies have assessed associations of DM with both total and site-specific cancers in Japan. We examined the association of a history of DM with cancer incidence in a population-based prospective cohort study in Japan. A total of 14 173 men and 16 547 women over 35 years old, who completed a self-administered baseline questionnaire in 1992, were followed up for cancer incidence from September 1992 to March 2008. At baseline, 6.3% men and 2.9% women had a history of diabetes. A total of 1974 men and 1514 women were identified as newly diagnosed with cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were determined using Cox proportional hazards models. After controlling for potential confounders, men with DM had a modest risk increase of total cancer occurrence compared with those without DM (HR, 1.09; 95% CI, 0.93-1.29). Increased risk of cancer of the liver (HR, 2.18; 95% CI, 1.27-3.74), bile duct (HR, 2.17; 95% CI, 1.01-4.66), and larynx (HR, 3.61; 95% CI, 1.16-11.2) in diabetic men were observed. In women, significant increased risk of total cancer (HR, 1.35; 95% CI, 1.06-1.73) and stomach cancer (HR, 2.15; 95% CI, 1.30-3.54) were observed among diabetic subjects. These data suggest that people with DM may be at increased risk of both total and some site-specific cancers.","Source":"PubMed","category":"HUMAN","training_data":"Diabetes mellitus and risk of cancer in Takayama: a population-based prospective cohort study in Japan Diabetes mellitus (DM) has been reported to be associated with an increased risk of site-specific cancers; however, few studies have assessed associations of DM with both total and site-specific cancers in Japan. We examined the association of a history of DM with cancer incidence in a population-based prospective cohort study in Japan. A total of 14 173 men and 16 547 women over 35 years old, who completed a self-administered baseline questionnaire in 1992, were followed up for cancer incidence from September 1992 to March 2008. At baseline, 6.3% men and 2.9% women had a history of diabetes. A total of 1974 men and 1514 women were identified as newly diagnosed with cancer. Hazard ratios (HR) and 95% confidence intervals (CI) were determined using Cox proportional hazards models. After controlling for potential confounders, men with DM had a modest risk increase of total cancer occurrence compared with those without DM (HR, 1.09; 95% CI, 0.93-1.29). Increased risk of cancer of the liver (HR, 2.18; 95% CI, 1.27-3.74), bile duct (HR, 2.17; 95% CI, 1.01-4.66), and larynx (HR, 3.61; 95% CI, 1.16-11.2) in diabetic men were observed. In women, significant increased risk of total cancer (HR, 1.35; 95% CI, 1.06-1.73) and stomach cancer (HR, 2.15; 95% CI, 1.30-3.54) were observed among diabetic subjects. These data suggest that people with DM may be at increased risk of both total and some site-specific cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"unresectable perihilar cholangiocarcinoma multimodal palliative treatment aim evaluate survival patients unresectable perihilar cholangiocarcinoma phc treated multimodal palliative approaches patients methods thirty two patients enrolled multimodal protocol including bilateral biliary drainage yridium 192 intraluminal brachytherapy bt metal biliary stenting external beam radiotherapy ebrt systemic chemotherapy cht patients underwent bt biliary stenting treatment 14 patients combined ebrt 11 ebrt cht seven mean median survival complication rates duration hospital stay calculated group results bt ebrt cht obtained best median 15 months one year 71 42 survival followed bt ebrt 14 months 63 63 respectively bt ebrt total dose 54 60 gy without cht led significantly higher median survival rate 14 months bt alone seven months conclusion bt ebrt without cht improves survival considered suitable alternative palliative surgery patients unresectable perihilar cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Unresectable Perihilar Cholangiocarcinoma: Multimodal Palliative Treatment","Abstract":"Aim: To evaluate the survival of patients with unresectable perihilar cholangiocarcinoma (PHC) treated with multimodal palliative approaches. \r\n\r\n Patients and methods: thirty-two patients were enrolled in a multimodal protocol including: bilateral biliary drainage; Yridium-192 intraluminal brachytherapy (BT); metal biliary stenting; external-beam radiotherapy (EBRT); systemic chemotherapy (ChT). All patients underwent BT and biliary stenting: this was the only treatment for 14 patients, it was combined with EBRT in 11, and with EBRT and ChT in seven. Mean and median survival, complication rates and duration of hospital stay were calculated for each group. \r\n\r\n Results: BT with EBRT and ChT obtained the best median (15 months) and one year (71.42%) survival followed by BT with EBRT (14 months and 63.63%, respectively). BT with EBRT in a total dose of 54-60 Gy, with or without ChT, led to a significantly higher median survival rate (14 months) than that for BT alone (seven months). \r\n\r\n Conclusion: BT with EBRT, with or without ChT, improves survival and should be considered as a suitable alternative to palliative surgery for patients with unresectable perihilar cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Unresectable Perihilar Cholangiocarcinoma: Multimodal Palliative Treatment Aim: To evaluate the survival of patients with unresectable perihilar cholangiocarcinoma (PHC) treated with multimodal palliative approaches. \r\n\r\n Patients and methods: thirty-two patients were enrolled in a multimodal protocol including: bilateral biliary drainage; Yridium-192 intraluminal brachytherapy (BT); metal biliary stenting; external-beam radiotherapy (EBRT); systemic chemotherapy (ChT). All patients underwent BT and biliary stenting: this was the only treatment for 14 patients, it was combined with EBRT in 11, and with EBRT and ChT in seven. Mean and median survival, complication rates and duration of hospital stay were calculated for each group. \r\n\r\n Results: BT with EBRT and ChT obtained the best median (15 months) and one year (71.42%) survival followed by BT with EBRT (14 months and 63.63%, respectively). BT with EBRT in a total dose of 54-60 Gy, with or without ChT, led to a significantly higher median survival rate (14 months) than that for BT alone (seven months). \r\n\r\n Conclusion: BT with EBRT, with or without ChT, improves survival and should be considered as a suitable alternative to palliative surgery for patients with unresectable perihilar cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"association bmi gallbladder cancer risk meta analysis obesity known cause gallstone formation gallstones increases risk gallbladder cancer gbc relation body mass index bmi gbc remains incompletely understood help elucidate role obesity gbc performed meta analysis relationship bmi gbc risk pubmed embase databases searched april 17 2016 fifteen articles 5902 cases identified random effects models dose response meta analyses used pool study results compared normal weight pooled relative risks rrs corresponding 95 confidence intervals ci gbc overweight obesity 1 10 0 98 1 23 1 58 1 43 1 75 respectively rrs 95 ci overweight obesity man 0 98 0 90 1 08 1 43 1 19 1 71 corresponding rrs woman 1 29 1 08 1 55 1 68 1 41 2 00 compared normal weight nonlinear dose response relationship bmi risk gbc found p 0 001 risk increased 4 1 kg m2 increment bmi adjusted sex point bmi 25 kg m2 rrs 95 cis women men 1 13 1 01 1 25 0 98 0 90 1 07 respectively corresponding rrs 95 cis point bmi 30 kg m2 1 56 1 39 1 75 vs 1 24 1 06 1 44 results suggest association obesity risk gbc stronger woman furthermore overweight associated gbc woman even stricter weight control might necessary woman prevent gbc pubmed","probabilities":0.9799733,"Title":"The association between BMI and gallbladder cancer risk: a meta-analysis","Abstract":"Obesity is a known cause of gallstone formation and gallstones increases the risk of gallbladder cancer (GBC), but the relation of body mass index (BMI) to GBC remains incompletely understood. To help elucidate the role of obesity in GBC, we performed a meta-analysis of the relationship between BMI and GBC risk. PUBMED and EMBASE databases were searched up to April 17, 2016. Fifteen articles with 5902 cases were identified. Random-effects models and dose-response meta-analyses were used to pool study results. Compared to normal weight, the pooled relative risks (RRs) and the corresponding 95% confidence intervals (CI) of GBC for overweight and obesity is 1.10 (0.98-1.23) and 1.58 (1.43-1.75) respectively. The RRs and 95% CI of overweight and obesity in man are 0.98 (0.90-1.08) and 1.43 (1.19-1.71), while the corresponding RRs in woman are 1.29 (1.08-1.55) and 1.68 (1.41-2.00) when compared to normal weight. A nonlinear dose-response relationship between BMI and risk of GBC was found (P=0.001), and the risk increased by 4% for each 1 kg/m2 increment in BMI. When adjusted for sex, at the point of BMI=25 kg/m2, the RRs (95% CIs) for women and men were 1.13 (1.01-1.25) and 0.98 (0.90-1.07) respectively. The corresponding RRs (95%CIs) at the point of BMI=30 kg/m2 were 1.56(1.39-1.75) vs. 1.24(1.06-1.44). These results suggest that association of obesity and risk of GBC is stronger in woman. Furthermore, overweight is only associated with GBC in woman. A even stricter weight control might be necessary for woman to prevent GBC.","Source":"PubMed","category":"HUMAN","training_data":"The association between BMI and gallbladder cancer risk: a meta-analysis Obesity is a known cause of gallstone formation and gallstones increases the risk of gallbladder cancer (GBC), but the relation of body mass index (BMI) to GBC remains incompletely understood. To help elucidate the role of obesity in GBC, we performed a meta-analysis of the relationship between BMI and GBC risk. PUBMED and EMBASE databases were searched up to April 17, 2016. Fifteen articles with 5902 cases were identified. Random-effects models and dose-response meta-analyses were used to pool study results. Compared to normal weight, the pooled relative risks (RRs) and the corresponding 95% confidence intervals (CI) of GBC for overweight and obesity is 1.10 (0.98-1.23) and 1.58 (1.43-1.75) respectively. The RRs and 95% CI of overweight and obesity in man are 0.98 (0.90-1.08) and 1.43 (1.19-1.71), while the corresponding RRs in woman are 1.29 (1.08-1.55) and 1.68 (1.41-2.00) when compared to normal weight. A nonlinear dose-response relationship between BMI and risk of GBC was found (P=0.001), and the risk increased by 4% for each 1 kg/m2 increment in BMI. When adjusted for sex, at the point of BMI=25 kg/m2, the RRs (95% CIs) for women and men were 1.13 (1.01-1.25) and 0.98 (0.90-1.07) respectively. The corresponding RRs (95%CIs) at the point of BMI=30 kg/m2 were 1.56(1.39-1.75) vs. 1.24(1.06-1.44). These results suggest that association of obesity and risk of GBC is stronger in woman. Furthermore, overweight is only associated with GBC in woman. A even stricter weight control might be necessary for woman to prevent GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"novel tff2 splice variant ex2tff2 correlates longer overall survival time cholangiocarcinoma trefoil factor 2 tff2 member trefoil factor family found overexpressed many cancers including cholangiocarcinoma cca majority studies focused wild type tff2 wttff2 expression information regarding alternative splicing variants tff2 mrna reported study aimed identify quantify novel tff2 splice variant cholangiocarcinoma cca seventy eight tumors 15 normal adjacent tissues quantified expression tff2 splice variant relative wild type wt tff2 mrna using quantitative reverse transcriptase polymerase chain reaction qrt pcr ratio tff2 splice variant wttff2 analyzed associations clinical parameters found novel tff2 splice variant exon 2 skipping ex2tff2 resulting stop codon tag exon 1 ex2tff2 wttff2 ratio tumors significantly higher normal tissue p 0 01 interestingly high ex2tff2 wttff2 ratio significantly associated good prognosis compared low ratio p 0 017 contrast presence wttff2 protein associated poor survival cca patients p 0 034 first report trefoil factor splice variant potential application prognostic biomarker cca pubmed","probabilities":0.9285714,"Title":"A novel TFF2 splice variant (∆EX2TFF2) correlates with longer overall survival time in cholangiocarcinoma","Abstract":"Trefoil factor 2 (TFF2) is a member of trefoil factor family found to be overexpressed in many cancers including cholangiocarcinoma (CCA). The majority of studies have focused on wild-type TFF2 (wtTFF2) expression, but information regarding alternative splicing variants of TFF2 mRNA has not been reported. In this study, we aimed to identify and quantify a novel TFF2 splice variant in cholangiocarcinoma (CCA). Seventy-eight tumors and 15 normal adjacent tissues were quantified for the expression of the TFF2 splice variant relative to wild-type (wt) TFF2 mRNA using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). The ratio of TFF2 splice variant against wtTFF2 was analyzed for associations with clinical parameters. We found a novel TFF2 splice variant, exon 2 skipping (∆EX2TFF2), resulting in a stop codon (TAG) at exon 1. The ∆EX2TFF2/wtTFF2 ratio in tumors was significantly higher than in normal tissue (P<0.01). Interestingly, high ∆EX2TFF2/wtTFF2 ratio was significantly associated with good prognosis compared with low ratio (P=0.017). In contrast, the presence of wtTFF2 protein was associated with poor survival of CCA patients (P=0.034). This is the first report of a trefoil factor splice variant and its potential application as a prognostic biomarker in CCA.","Source":"PubMed","category":"ANIMAL","training_data":"A novel TFF2 splice variant (∆EX2TFF2) correlates with longer overall survival time in cholangiocarcinoma Trefoil factor 2 (TFF2) is a member of trefoil factor family found to be overexpressed in many cancers including cholangiocarcinoma (CCA). The majority of studies have focused on wild-type TFF2 (wtTFF2) expression, but information regarding alternative splicing variants of TFF2 mRNA has not been reported. In this study, we aimed to identify and quantify a novel TFF2 splice variant in cholangiocarcinoma (CCA). Seventy-eight tumors and 15 normal adjacent tissues were quantified for the expression of the TFF2 splice variant relative to wild-type (wt) TFF2 mRNA using quantitative reverse transcriptase polymerase chain reaction (QRT-PCR). The ratio of TFF2 splice variant against wtTFF2 was analyzed for associations with clinical parameters. We found a novel TFF2 splice variant, exon 2 skipping (∆EX2TFF2), resulting in a stop codon (TAG) at exon 1. The ∆EX2TFF2/wtTFF2 ratio in tumors was significantly higher than in normal tissue (P<0.01). Interestingly, high ∆EX2TFF2/wtTFF2 ratio was significantly associated with good prognosis compared with low ratio (P=0.017). In contrast, the presence of wtTFF2 protein was associated with poor survival of CCA patients (P=0.034). This is the first report of a trefoil factor splice variant and its potential application as a prognostic biomarker in CCA. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"trail combination subtoxic 5 fu effectively inhibit cell proliferation induce apoptosis cholangiocarcinoma cells past decade incidence mortality rates cholangiocarcinoma cca increasing worldwide relatively low responsiveness cca conventional chemotherapy leads poor overall survival recently tumor necrosis factor related apoptosis inducing ligand trail apo2l emerged promising anti cancer therapeutic agent since able selectively induce apoptosis tumor cells normal cells study aimed investigate therapeutic effect trail cca cell lines m213 m214 kku100 compared immortal biliary cell line mmnk1 either alone combination subtoxic dose 5 fluorouracil 5 fu found recombinant human trail rhtrail potential agent significantly inhibited cell proliferation mediated caspase activities caspases 8 9 3 7 apoptosis cca cells combined treatment rhtrail 5 fu effectively enhanced inhibition cca cell growth smaller effect mmnk1 finding suggests trail novel anti cancer therapeutic agent advantage combination conventional chemotherapeutic drug effective treatment cca stn","probabilities":0.9467213,"Title":"Trail In Combination With Subtoxic 5-Fu Effectively Inhibit Cell Proliferation And Induce Apoptosis In Cholangiocarcinoma Cells","Abstract":"In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA.","Source":"STN","category":"ANIMAL","training_data":"Trail In Combination With Subtoxic 5-Fu Effectively Inhibit Cell Proliferation And Induce Apoptosis In Cholangiocarcinoma Cells In the past decade, the incidence and mortality rates of cholangiocarcinoma (CCA) have been increasing worldwide. The relatively low responsiveness of CCA to conventional chemotherapy leads to poor overall survival. Recently, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL or Apo2L) has emerged as the most promising anti-cancer therapeutic agent since it is able to selectively induce apoptosis of tumor cells but not normal cells. In this study, we aimed to investigate the therapeutic effect of TRAIL in CCA cell lines (M213, M214 and KKU100) compared with the immortal biliary cell line, MMNK1, either alone or in combination with a subtoxic dose of 5-fluorouracil (5-FU). We found that recombinant human TRAIL (rhTRAIL) was a potential agent which significantly inhibited cell proliferation and mediated caspase activities (caspases 8, 9 and 3/7) and apoptosis of CCA cells. The combined treatment of rhTRAIL and 5-FU effectively enhanced inhibition of CCA cell growth with a smaller effect on MMNK1. Our finding suggests TRAIL to be a novel anti-cancer therapeutic agent and advantage of its combination with a conventional chemotherapeutic drug for effective treatment of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"true prognosis resected distal cholangiocarcinoma background prognosis distal cholangiocarcinoma dcc pancreaticoduodenectomy pd remains poorly assessed aims study describe oncological results pd dcc compare prognosis pancreatic ductal adenocarcinoma pdac methods pd periampullary carcinoma performed january 2000 march 2013 extracted prospective database risk factors likely influence overall os disease free dfs survivals dcc assessed multivariable analyses dcc pdac prognoses compared matching using propensity score nearest neighbor matching results 290 patients analyzed 56 dcc mean age 65 15 years median os 36 9 months recurrence occurred 35 patients 67 mostly liver 37 median dfs 14 6 months combined organ resection independent risk factor worse os dfs p 0 01 p 0 001 respectively matching analysis found significant difference dcc pdac terms os p 0 284 dfs p 0 438 conclusion first propensity analysis demonstrated dcc pdac prognosis linked high rate early recurrence particularly associated need combined organ resection j surg oncol 2016 113 575 580 2016 wiley periodicals inc pubmed","probabilities":0.9799733,"Title":"The true prognosis of resected distal cholangiocarcinoma","Abstract":"BACKGROUND: Prognosis of distal cholangiocarcinoma (DCC) after pancreaticoduodenectomy (PD) remains poorly assessed. The aims of this study were to describe the oncological results of PD in DCC and to compare its prognosis to pancreatic ductal adenocarcinoma (PDAC). METHODS: All PD for periampullary carcinoma performed between January 2000 and March 2013 were extracted from a prospective database. Risk factors likely to influence overall (OS) and disease-free (DFS) survivals of DCC were assessed by multivariable analyses. The DCC and PDAC prognoses were compared after matching using propensity score (nearest neighbor matching). RESULTS: Of the 290 patients analyzed, 56 had DCC, with a mean age of 65 ± 15 years. The median OS was 36.9 months. Recurrence occurred in 35 patients (67%), mostly in the liver (37%). The median DFS was 14.6 months. Combined organ resection was an independent risk factor for worse OS and DFS (P = 0.01 and P = 0.001, respectively). Matching analysis found no significant difference between DCC and PDAC in terms of OS (P = 0.284) or DFS (P = 0.438). CONCLUSION: This first propensity analysis demonstrated that DCC and PDAC have the same prognosis, linked to the high rate of early recurrence, particularly associated with the need for combined organ resection. J. Surg. Oncol. 2016;113:575-580. © 2016 Wiley Periodicals, Inc.","Source":"PubMed","category":"HUMAN","training_data":"The true prognosis of resected distal cholangiocarcinoma BACKGROUND: Prognosis of distal cholangiocarcinoma (DCC) after pancreaticoduodenectomy (PD) remains poorly assessed. The aims of this study were to describe the oncological results of PD in DCC and to compare its prognosis to pancreatic ductal adenocarcinoma (PDAC). METHODS: All PD for periampullary carcinoma performed between January 2000 and March 2013 were extracted from a prospective database. Risk factors likely to influence overall (OS) and disease-free (DFS) survivals of DCC were assessed by multivariable analyses. The DCC and PDAC prognoses were compared after matching using propensity score (nearest neighbor matching). RESULTS: Of the 290 patients analyzed, 56 had DCC, with a mean age of 65 ± 15 years. The median OS was 36.9 months. Recurrence occurred in 35 patients (67%), mostly in the liver (37%). The median DFS was 14.6 months. Combined organ resection was an independent risk factor for worse OS and DFS (P = 0.01 and P = 0.001, respectively). Matching analysis found no significant difference between DCC and PDAC in terms of OS (P = 0.284) or DFS (P = 0.438). CONCLUSION: This first propensity analysis demonstrated that DCC and PDAC have the same prognosis, linked to the high rate of early recurrence, particularly associated with the need for combined organ resection. J. Surg. Oncol. 2016;113:575-580. © 2016 Wiley Periodicals, Inc. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ace2 fzd1 prognosis markers squamous cell adenosquamous carcinoma adenocarcinoma gallbladder clinicopathological characteristics squamous cell adenosquamous carcinoma sc asc gallbladder well documented prognosis marker identified rare occurrence gallbladder cancer subtype study examined ace2 fzd1 expression 46 sc ascs 80 adenocarcinomas using immunohistochemistry analyzed correlations clinicopathological characteristics demonstrated positive fzd1 negative ace2 expression significantly associated large tumor size high tnm stage lymph node metastasis invasion sc asc ac univariate kaplan meier analysis showed positive fzd1 negative ace2 expression well differentiation tumor size tnm stage lymph node metastasis invasion surgical curability closely associated decreased overall survival sc asc p 0 001 ac p 0 001 patients average survival time sc asc ac patients fzd1 ace2 expression significantly longer patients fzd1 ace2 fzd1 ace2 p 0 01 multivariate cox regression analysis showed positive fzd1 negative ace2 expression independent poor prognostic factors sc asc ac patients addition fzd1 expression positively ace2 expression negatively correlated expression ca19 9 sc asc ac study suggested positive fzd1 negative ace2 expression closely related expression ca19 9 clinical pathological biological behaviors well poor prognosis gallbladder cancer stn","probabilities":1.0,"Title":"Ace2 And Fzd1 Are Prognosis Markers In Squamous Cell/Adenosquamous Carcinoma And Adenocarcinoma Of Gallbladder","Abstract":"The clinicopathological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder have not been well documented, and no prognosis marker has been identified because of the rare occurrence of this gallbladder cancer subtype. In this study, we examined ACE2 and FZD1 expression in 46 SC/ASCs and 80 adenocarcinomas using immunohistochemistry and further analyzed their correlations with clinicopathological characteristics. We demonstrated that positive FZD1 and negative ACE2 expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis and invasion of SC/ASC and AC. Univariate Kaplan-Meier analysis showed that positive FZD1 and negative ACE2 expression as well as differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical curability were closely associated with decreased overall survival in both SC/ASC (p < 0.001) and AC (p < 0.001) patients. The average survival time in SC/ASC and AC patients with FZD1(-)ACE2(+) expression was significantly longer than that in patients with FZD1(+)ACE2(-) or FZD1(+)ACE2(+) (p < 0.01). Multivariate Cox regression analysis showed that positive FZD1 and negative ACE2 expression are independent poor-prognostic factors for both SC/ASC and AC patients. In addition, FZD1 expression positively, but ACE2 expression negatively correlated with the expression of CA19-9 in SC/ASC and AC. Our study suggested that positive FZD1 and negative ACE2 expression are closely related to the expression of CA19-9; clinical, pathological, and biological behaviors; as well as poor-prognosis of gallbladder cancer.","Source":"STN","category":"HUMAN","training_data":"Ace2 And Fzd1 Are Prognosis Markers In Squamous Cell/Adenosquamous Carcinoma And Adenocarcinoma Of Gallbladder The clinicopathological characteristics of squamous cell/adenosquamous carcinoma (SC/ASC) of the gallbladder have not been well documented, and no prognosis marker has been identified because of the rare occurrence of this gallbladder cancer subtype. In this study, we examined ACE2 and FZD1 expression in 46 SC/ASCs and 80 adenocarcinomas using immunohistochemistry and further analyzed their correlations with clinicopathological characteristics. We demonstrated that positive FZD1 and negative ACE2 expression were significantly associated with large tumor size, high TNM stage, lymph node metastasis and invasion of SC/ASC and AC. Univariate Kaplan-Meier analysis showed that positive FZD1 and negative ACE2 expression as well as differentiation, tumor size, TNM stage, lymph node metastasis, invasion, and surgical curability were closely associated with decreased overall survival in both SC/ASC (p < 0.001) and AC (p < 0.001) patients. The average survival time in SC/ASC and AC patients with FZD1(-)ACE2(+) expression was significantly longer than that in patients with FZD1(+)ACE2(-) or FZD1(+)ACE2(+) (p < 0.01). Multivariate Cox regression analysis showed that positive FZD1 and negative ACE2 expression are independent poor-prognostic factors for both SC/ASC and AC patients. In addition, FZD1 expression positively, but ACE2 expression negatively correlated with the expression of CA19-9 in SC/ASC and AC. Our study suggested that positive FZD1 and negative ACE2 expression are closely related to the expression of CA19-9; clinical, pathological, and biological behaviors; as well as poor-prognosis of gallbladder cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"intensity modulated radiotherapy following null margin resection associated improved survival treatment intrahepatic cholangiocarcinoma background current study first examine effectiveness toxicity postoperative intensity modulated radiotherapy imrt treatment intrahepatic cholangiocarcinoma icc abutting vasculature specifically aim assess role imrt patients icc undergoing null margin real resection margin resection methods thirty eight patients icc adherent major blood vessels included retrospective study null margin resection performed patients 14 patients treated imrt median radiation dose delivered 56 8 gy range 50 60 gy primary endpoints overall survival os disease free survival dfs results median follow 24 6 months median os dfs patients n 38 17 7 months 95 ci 13 2 22 2 9 9 months 95 ci 2 8 17 0 respectively median os 21 8 months 95 ci 15 5 28 1 among 14 patients postoperative imrt group 15 0 months 95 ci 9 2 20 9 among 24 patients surgery group p 0 049 median dfs 12 5 months 95 ci 6 8 18 2 postoperative imrt group 5 5 months 95 ci 0 7 12 3 surgery group p 0 081 imrt well tolerated acute toxicity included one case grade 3 leukopenia late toxicity included one case asymptomatic duodenal ulcer discovered endoscopy conclusions study results suggest postoperative imrt safe effective treatment option following null margin resections icc larger prospective randomized trials necessary establish postoperative imrt standard practice treatment icc adherent major hepatic vessels stn","probabilities":0.9799733,"Title":"Intensity-Modulated Radiotherapy Following Null-Margin Resection Is Associated With Improved Survival In The Treatment Of Intrahepatic Cholangiocarcinoma","Abstract":"Background: The current study is the first to examine the effectiveness and toxicity of postoperative intensity-modulated radiotherapy (IMRT) in the treatment of intrahepatic cholangiocarcinoma (ICC) abutting the vasculature. Specifically, we aim to assess the role of IMRT in patients with ICC undergoing null-margin (no real resection margin) resection. \r\n\r\n Methods: Thirty-eight patients with ICC adherent to major blood vessels were included in this retrospective study. Null-margin resection was performed on all patients; 14 patients were further treated with IMRT. The median radiation dose delivered was 56.8 Gy (range, 50-60 Gy). The primary endpoints were overall survival (OS) and disease-free survival (DFS). \r\n\r\n Results: At a median follow-up of 24.6 months, the median OS and DFS of all patients (n=38) were 17.7 months (95% CI, 13.2-22.2) and 9.9 months (95% CI, 2.8-17.0), respectively. Median OS was 21.8 months (95% CI, 15.5-28.1) among the 14 patients in the postoperative IMRT group and 15.0 months (95% CI, 9.2-20.9) among the 24 patients in the surgery-only group (P=0.049). Median DFS was 12.5 months (95% CI, 6.8-18.2) in the postoperative IMRT group and 5.5 months (95% CI, 0.7-12.3) in the surgery-only group (P=0.081). IMRT was well-tolerated. Acute toxicity included one case of Grade 3 leukopenia; late toxicity included one case of asymptomatic duodenal ulcer discovered through endoscopy. \r\n\r\n Conclusions: The study results suggest that postoperative IMRT is a safe and effective treatment option following null-margin resections of ICC. Larger prospective and randomized trials are necessary to establish postoperative IMRT as a standard practice for the treatment of ICC adherent to major hepatic vessels.","Source":"STN","category":"HUMAN","training_data":"Intensity-Modulated Radiotherapy Following Null-Margin Resection Is Associated With Improved Survival In The Treatment Of Intrahepatic Cholangiocarcinoma Background: The current study is the first to examine the effectiveness and toxicity of postoperative intensity-modulated radiotherapy (IMRT) in the treatment of intrahepatic cholangiocarcinoma (ICC) abutting the vasculature. Specifically, we aim to assess the role of IMRT in patients with ICC undergoing null-margin (no real resection margin) resection. \r\n\r\n Methods: Thirty-eight patients with ICC adherent to major blood vessels were included in this retrospective study. Null-margin resection was performed on all patients; 14 patients were further treated with IMRT. The median radiation dose delivered was 56.8 Gy (range, 50-60 Gy). The primary endpoints were overall survival (OS) and disease-free survival (DFS). \r\n\r\n Results: At a median follow-up of 24.6 months, the median OS and DFS of all patients (n=38) were 17.7 months (95% CI, 13.2-22.2) and 9.9 months (95% CI, 2.8-17.0), respectively. Median OS was 21.8 months (95% CI, 15.5-28.1) among the 14 patients in the postoperative IMRT group and 15.0 months (95% CI, 9.2-20.9) among the 24 patients in the surgery-only group (P=0.049). Median DFS was 12.5 months (95% CI, 6.8-18.2) in the postoperative IMRT group and 5.5 months (95% CI, 0.7-12.3) in the surgery-only group (P=0.081). IMRT was well-tolerated. Acute toxicity included one case of Grade 3 leukopenia; late toxicity included one case of asymptomatic duodenal ulcer discovered through endoscopy. \r\n\r\n Conclusions: The study results suggest that postoperative IMRT is a safe and effective treatment option following null-margin resections of ICC. Larger prospective and randomized trials are necessary to establish postoperative IMRT as a standard practice for the treatment of ICC adherent to major hepatic vessels. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic values prevalent gene mutations intrahepatic cholangiocarcinoma abstract intrahepatic cholangiocarcinoma icc complicated fatal cancer development sequencing technologies tp53 kras idh1 2 identified frequently mutant genes icc however prognostic value mutations remained uncertain order clarify prognostic values mutant genes icc systematic search pubmed embase web science performed publications met inclusion exclusion criteria finally included hazard ratio hr 95 confidence interval cis tp53 kras idh1 2 mutation overall survival os extracted eligible study also odds ratio 95 ci gene mutations clinical features extracted i2 2 tests applied assess heterogeneity enrolled studies p 0 05 indicated statistical significance p 0 05 used fixed effects model calculate pooled hr assess association gene mutation overall survival p 0 05 used random effects model addition pooled calculated investigate correlation gene mutation clinical features icc total 16 studies composing 1 516 icc patients included final analysis eight articles studied relationship tp53 mutation overall survival indicating patients tp53 mutation poorer prognosis hr 2 91 95 ci 1 67 5 09 meta analysis eleven studies revealed kras mutation adverse prognostic predictor icc hr 2 30 95 ci 1 70 3 12 result seven studies showed idh1 2 mutation impact prognosis icc patients hr 1 02 95 ci 0 62 1 67 however subgroup analysis suggested idh1 2 mutation favorable prognostic factor patients asia hr 0 53 95 ci 0 33 0 87 shortened overall survival patients america europe hr 1 41 95 ci 1 05 1 90 also found kras mutation associated progressive tumor stage iii iv 0 31 95 ci 0 15 0 63 patients idh1 2 mutation tended poor tumor differentiation 0 41 95 ci 0 19 0 90 findings indicated different prognostic roles tp53 kras idh1 2 mutations icc google scholar","probabilities":0.9799733,"Title":"Prognostic Values Of Prevalent Gene Mutations In Intrahepatic Cholangiocarcinoma","Abstract":"Abstract: Intrahepatic cholangiocarcinoma (ICC) is a complicated and fatal cancer. With the development of sequencing technologies, TP53, KRAS and IDH1/2 have been identified as frequently mutant genes in ICC. However, the prognostic value of these mutations remained uncertain. In order to clarify the prognostic values of these mutant genes in ICC, a systematic search of Pubmed, Embase and Web of Science was performed. Publications which met inclusion and exclusion criteria were finally included. The hazard ratio (HR) and 95% confidence interval (CIs) of TP53, KRAS, and IDH1/2 mutation for overall survival (OS) was extracted from each eligible study. Also, the odds ratio (OR) and 95% CI of these gene mutations for clinical features was extracted. The I2 and χ2 tests were applied to assess heterogeneity between the enrolled studies, and P<0.05 indicated statistical significance. If P>0.05, we used a fixed-effects model to calculate the pooled HR to assess the association between gene mutation and overall survival; and if P<0.05, we used a random-effects model. In addition, the pooled OR was calculated to investigate the correlation between gene mutation and clinical features in ICC. A total of 16 studies composing of 1,516 ICC patients were included in the final analysis. Eight articles studied the relationship between TP53 mutation and overall survival, indicating that patients with TP53 mutation had poorer prognosis (HR=2.91, 95% CI: 1.67-5.09). And meta-analysis of eleven studies revealed that KRAS mutation was an adverse prognostic predictor in ICC (HR=2.30, 95% CI: 1.70-3.12). The result of seven studies showed that IDH1/2 mutation had no impact on prognosis of ICC patients (HR=1.02, 95% CI: 0.62-1.67). However, the subgroup analysis suggested that IDH1/2 mutation was a favorable prognostic factor in patients from Asia (HR=0.53, 95% CI: 0.33-0.87), but it could shortened overall survival in patients from America and Europe (HR=1.41, 95% CI: 1.05-1.90). We also found that KRAS mutation was associated with progressive tumor stage (III-IV) (OR=0.31, 95% CI: 0.15-0.63), and that patients with IDH1/2 mutation tended to have poor tumor differentiation (OR=0.41, 95% CI: 0.19-0.90). These findings indicated there are different prognostic roles of TP53, KRAS and IDH1/2 mutations in ICC.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Values Of Prevalent Gene Mutations In Intrahepatic Cholangiocarcinoma Abstract: Intrahepatic cholangiocarcinoma (ICC) is a complicated and fatal cancer. With the development of sequencing technologies, TP53, KRAS and IDH1/2 have been identified as frequently mutant genes in ICC. However, the prognostic value of these mutations remained uncertain. In order to clarify the prognostic values of these mutant genes in ICC, a systematic search of Pubmed, Embase and Web of Science was performed. Publications which met inclusion and exclusion criteria were finally included. The hazard ratio (HR) and 95% confidence interval (CIs) of TP53, KRAS, and IDH1/2 mutation for overall survival (OS) was extracted from each eligible study. Also, the odds ratio (OR) and 95% CI of these gene mutations for clinical features was extracted. The I2 and χ2 tests were applied to assess heterogeneity between the enrolled studies, and P<0.05 indicated statistical significance. If P>0.05, we used a fixed-effects model to calculate the pooled HR to assess the association between gene mutation and overall survival; and if P<0.05, we used a random-effects model. In addition, the pooled OR was calculated to investigate the correlation between gene mutation and clinical features in ICC. A total of 16 studies composing of 1,516 ICC patients were included in the final analysis. Eight articles studied the relationship between TP53 mutation and overall survival, indicating that patients with TP53 mutation had poorer prognosis (HR=2.91, 95% CI: 1.67-5.09). And meta-analysis of eleven studies revealed that KRAS mutation was an adverse prognostic predictor in ICC (HR=2.30, 95% CI: 1.70-3.12). The result of seven studies showed that IDH1/2 mutation had no impact on prognosis of ICC patients (HR=1.02, 95% CI: 0.62-1.67). However, the subgroup analysis suggested that IDH1/2 mutation was a favorable prognostic factor in patients from Asia (HR=0.53, 95% CI: 0.33-0.87), but it could shortened overall survival in patients from America and Europe (HR=1.41, 95% CI: 1.05-1.90). We also found that KRAS mutation was associated with progressive tumor stage (III-IV) (OR=0.31, 95% CI: 0.15-0.63), and that patients with IDH1/2 mutation tended to have poor tumor differentiation (OR=0.41, 95% CI: 0.19-0.90). These findings indicated there are different prognostic roles of TP53, KRAS and IDH1/2 mutations in ICC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"survival prognostic factors pancreatic ampullary cancer aim analyzed survival patients diagnosed ampullary cancer ac pancreatic ductal adenocarcinomas pdac patients methods 1996 2009 505 69 patients diagnosed pdac ac respectively identified overall survival analyzed according tumor entity therapeutic approach pathological tumor stage results 5 year overall survival rate patients ac 37 95 confidence interval 25 49 remarkably higher compared pdac patients 7 95 confidence interval 5 10 cohorts surgical resection improved survival analysis pathological factors revealed survival benefit patients staged small primary tumors pt1 2 exclusion distant metastases m0 pdac ac interestingly absence lymph node metastasis substantially improved survival ac pdac conclusion overall survival patients ac superior compared patients pdac therapeutically adequate regional lymph node dissection seems particularly important surgical management ac pubmed","probabilities":0.9799733,"Title":"Survival and prognostic factors in pancreatic and ampullary cancer","Abstract":"AIM: We analyzed survival of patients diagnosed with ampullary cancer (AC) and pancreatic ductal adenocarcinomas (PDAC). PATIENTS AND METHODS: Between 1996 and 2009, 505 and 69 patients diagnosed with PDAC and AC, respectively, were identified. Overall survival was analyzed according to tumor entity, therapeutic approach and pathological tumor stage. RESULTS: The 5-year overall survival rate of patients with AC (37%; 95% confidence interval 25-49%) was remarkably higher compared to PDAC patients (7%; 95% confidence interval 5-10%). In both cohorts, surgical resection improved survival. Analysis of pathological factors revealed a survival benefit for patients staged with small primary tumors (pT1/2) and exclusion of distant metastases (M0) for both PDAC and AC. Interestingly, absence of lymph node metastasis substantially improved survival in AC, but not in PDAC. CONCLUSION: Overall survival of patients with AC is superior compared to that of patients with PDAC. Therapeutically, adequate regional lymph node dissection seems particularly important for the surgical management of AC.","Source":"PubMed","category":"HUMAN","training_data":"Survival and prognostic factors in pancreatic and ampullary cancer AIM: We analyzed survival of patients diagnosed with ampullary cancer (AC) and pancreatic ductal adenocarcinomas (PDAC). PATIENTS AND METHODS: Between 1996 and 2009, 505 and 69 patients diagnosed with PDAC and AC, respectively, were identified. Overall survival was analyzed according to tumor entity, therapeutic approach and pathological tumor stage. RESULTS: The 5-year overall survival rate of patients with AC (37%; 95% confidence interval 25-49%) was remarkably higher compared to PDAC patients (7%; 95% confidence interval 5-10%). In both cohorts, surgical resection improved survival. Analysis of pathological factors revealed a survival benefit for patients staged with small primary tumors (pT1/2) and exclusion of distant metastases (M0) for both PDAC and AC. Interestingly, absence of lymph node metastasis substantially improved survival in AC, but not in PDAC. CONCLUSION: Overall survival of patients with AC is superior compared to that of patients with PDAC. Therapeutically, adequate regional lymph node dissection seems particularly important for the surgical management of AC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"validation histomolecular classification utilizing histological subtype muc1 cdx2 prognostication resected ampullary adenocarcinoma background outcomes ampullary adenocarcinomas heterogeneous numerous methods categorisation exist histomolecular phenotype based histology caudal type homeodomain transcription factor 2 cdx2 staining mucin 1 muc1 staining recently tested validated two cohorts attempt validate classification large patient population methods tissue samples 163 patients resected ampullary adenocarcinoma classified based histology immunohistochemical expression cdx2 muc1 pancreaticobiliary histomolecular classification pb defined sample pancreaticobiliary histology positive muc1 negative cdx2 expression results 82 deaths median follow 32 4 months median overall survival 87 7 95 ci 42 9 109 5 months pb comprised 28 2 cases factors associated overall survival histological subtype p 0 0340 t1 2 vs t3 4 p 0 001 perineural p 0 0001 lymphovascular p 0 0203 invasion histomolecular intestinal histomolecular phenotype int vs pb phenotype 106 4 vs 21 2 months p 0 0001 neither muc1 cdx2 statistically significant although muc1 positivity defined 10 staining significant p 0 0023 multivariate analysis age hr 1 03 pb phenotype hr 2 26 perineural invasion pni hr 2 26 associated poor survival conclusions prognostic ability histomolecular phenotype validated independent cohort ampullary adenocarcinoma patients pubmed","probabilities":0.7966102,"Title":"Validation of histomolecular classification utilizing histological subtype, MUC1, and CDX2 for prognostication of resected ampullary adenocarcinoma","Abstract":"BACKGROUND: Outcomes for ampullary adenocarcinomas are heterogeneous, and numerous methods of categorisation exist. A histomolecular phenotype based on histology, caudal-type homeodomain transcription factor 2 (CDX2) staining and Mucin 1 (MUC1) staining has recently been tested and validated in two cohorts. We attempt to validate this classification in a large patient population. METHODS: Tissue samples from 163 patients with resected ampullary adenocarcinoma were classified based on histology and immunohistochemical expression of CDX2 and MUC1. A pancreaticobiliary histomolecular classification (PB) was defined as a sample with pancreaticobiliary histology, positive MUC1 and negative CDX2 expression. RESULTS: There were 82 deaths; median follow-up of 32.4 months; and median overall survival of 87.7 (95% CI 42.9-109.5) months. PB comprised 28.2% of the cases. Factors associated with overall survival were histological subtype (P=0.0340); T1/2 vs T3/4 (P=0.001); perineural (P<0.0001) and lymphovascular (P=0.0203) invasion; and histomolecular intestinal histomolecular phenotype (INT) vs PB phenotype (106.4 vs 21.2 months, P<0.0001). Neither MUC1 nor CDX2 was statistically significant, although MUC1 positivity defined as ⩾10% staining was significant (P=0.0023). In multivariate analysis, age (HR 1.03), PB phenotype (HR 2.26) and perineural invasion (PNI; HR 2.26) were associated with poor survival. CONCLUSIONS: The prognostic ability of histomolecular phenotype has been validated in an independent cohort of ampullary adenocarcinoma patients.","Source":"PubMed","category":"HUMAN","training_data":"Validation of histomolecular classification utilizing histological subtype, MUC1, and CDX2 for prognostication of resected ampullary adenocarcinoma BACKGROUND: Outcomes for ampullary adenocarcinomas are heterogeneous, and numerous methods of categorisation exist. A histomolecular phenotype based on histology, caudal-type homeodomain transcription factor 2 (CDX2) staining and Mucin 1 (MUC1) staining has recently been tested and validated in two cohorts. We attempt to validate this classification in a large patient population. METHODS: Tissue samples from 163 patients with resected ampullary adenocarcinoma were classified based on histology and immunohistochemical expression of CDX2 and MUC1. A pancreaticobiliary histomolecular classification (PB) was defined as a sample with pancreaticobiliary histology, positive MUC1 and negative CDX2 expression. RESULTS: There were 82 deaths; median follow-up of 32.4 months; and median overall survival of 87.7 (95% CI 42.9-109.5) months. PB comprised 28.2% of the cases. Factors associated with overall survival were histological subtype (P=0.0340); T1/2 vs T3/4 (P=0.001); perineural (P<0.0001) and lymphovascular (P=0.0203) invasion; and histomolecular intestinal histomolecular phenotype (INT) vs PB phenotype (106.4 vs 21.2 months, P<0.0001). Neither MUC1 nor CDX2 was statistically significant, although MUC1 positivity defined as ⩾10% staining was significant (P=0.0023). In multivariate analysis, age (HR 1.03), PB phenotype (HR 2.26) and perineural invasion (PNI; HR 2.26) were associated with poor survival. CONCLUSIONS: The prognostic ability of histomolecular phenotype has been validated in an independent cohort of ampullary adenocarcinoma patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment cholangiocarcinoma hepatologist perspective cholangiocarcinoma cca rare lethal adenocarcinoma cholangiocyte differentiation arises within biliary tree variable locations curative options available form surgical resection liver transplantation lt early stage cca however offered small fraction patients usually asymptomatic remain undiagnosed primary sclerosing cholangitis psc well known risk factor cca cirrhosis viral hepatitis metabolic syndrome recently identified risk factors cca emerging evidence places hepatologists vital position diagnose prognosticate manage cca planning treatment individual patient based stage extent malignancy appropriate selection patients involvement multidisciplinary team surgical resection localized cca lt coupled neoadjuvant chemoradiation perihilar cca locoregional systemic chemotherapy endoscopic interventions advanced cca offered pubmed","probabilities":0.9799733,"Title":"The treatment of cholangiocarcinoma: a hepatologist's perspective","Abstract":"Cholangiocarcinoma (CCA) is a rare but lethal adenocarcinoma with cholangiocyte differentiation that arises within the biliary tree at variable locations. Curative options are available in the form of surgical resection and/or liver transplantation (LT) in early stage CCA; however, these are offered to a small fraction of patients as they are usually asymptomatic and remain undiagnosed. Primary sclerosing cholangitis (PSC) is a well-known risk factor of CCA, and cirrhosis, viral hepatitis, and metabolic syndrome are recently identified as risk factors of CCA. This emerging evidence places hepatologists in a vital position to diagnose, prognosticate, and manage CCA by planning treatment of each individual patient based on the stage and extent of malignancy. With appropriate selection of patients and the involvement of a multidisciplinary team, surgical resection of localized CCA, LT coupled with neoadjuvant chemoradiation for perihilar CCA, or locoregional or systemic chemotherapy and/or endoscopic interventions for advanced CCA can be offered.","Source":"PubMed","category":"HUMAN","training_data":"The treatment of cholangiocarcinoma: a hepatologist's perspective Cholangiocarcinoma (CCA) is a rare but lethal adenocarcinoma with cholangiocyte differentiation that arises within the biliary tree at variable locations. Curative options are available in the form of surgical resection and/or liver transplantation (LT) in early stage CCA; however, these are offered to a small fraction of patients as they are usually asymptomatic and remain undiagnosed. Primary sclerosing cholangitis (PSC) is a well-known risk factor of CCA, and cirrhosis, viral hepatitis, and metabolic syndrome are recently identified as risk factors of CCA. This emerging evidence places hepatologists in a vital position to diagnose, prognosticate, and manage CCA by planning treatment of each individual patient based on the stage and extent of malignancy. With appropriate selection of patients and the involvement of a multidisciplinary team, surgical resection of localized CCA, LT coupled with neoadjuvant chemoradiation for perihilar CCA, or locoregional or systemic chemotherapy and/or endoscopic interventions for advanced CCA can be offered. PubMed","prediction_labels":"HUMAN"},{"cleaned":"sparcl1 novel predictor tumor recurrence survival hilar cholangiocarcinoma secreted protein acidic rich cysteines like protein 1 sparcl1 implicated tumor initiation formation progression various cancers yet role hilar cholangiocarcinoma remains largely uncharacterized present study tissue microarrays containing resected hilar cholangiocarcinoma specimens 92 patients used evaluate expression sparcl1 protein immunohistochemistry ihc vitro assays used determine effect sparcl1 overexpression cell growth migration loss sparcl1 expression observed 46 50 0 92 primary tumors sparcl1 expression inversely associated poorly undifferentiation specimens p 0 030 addition lymph node metastasis p 0 047 survival analysis demonstrated sparcl1 independent factor predicting outcome patients hilar cholangiocarcinoma sparcl1 overexpression suppressed tumor cell migration vitro inhibiting mmp 9 mmp 2 vimentin fibronectin expression whereas inhibit cell proliferation vitro results suggest loss sparcl1 involved tumorigenesis hilar cholangiocarcinoma may serve novel molecular biomarker patients outcome stn","probabilities":0.9467213,"Title":"Sparcl1 Is A Novel Predictor Of Tumor Recurrence And Survival In Hilar Cholangiocarcinoma","Abstract":"Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1) has been implicated in tumor initiation, formation, and progression of various cancers, yet its role in hilar cholangiocarcinoma remains largely uncharacterized. In the present study, tissue microarrays containing resected hilar cholangiocarcinoma specimens from 92 patients were used to evaluate the expression of SPARCL1 protein by immunohistochemistry (IHC). In vitro assays were used to determine the effect of SPARCL1 overexpression on cell growth and migration. Loss of SPARCL1 expression was observed in 46 (50.0 %) of the 92 primary tumors. SPARCL1 expression is inversely associated with poorly or undifferentiation specimens (P = 0.030) in addition to lymph node metastasis (P = 0.047). Survival analysis demonstrated that SPARCL1 is an independent factor in predicting the outcome of patients with hilar cholangiocarcinoma. SPARCL1 overexpression suppressed tumor cell migration in vitro by inhibiting MMP-9, MMP-2, Vimentin, and Fibronectin expression, whereas did not inhibit cell proliferation in vitro. Our results suggest that loss of SPARCL1 is involved in the tumorigenesis of hilar cholangiocarcinoma and may serve as a novel molecular biomarker for patients' outcome.","Source":"STN","category":"ANIMAL","training_data":"Sparcl1 Is A Novel Predictor Of Tumor Recurrence And Survival In Hilar Cholangiocarcinoma Secreted protein acidic and rich in cysteines-like protein 1 (SPARCL1) has been implicated in tumor initiation, formation, and progression of various cancers, yet its role in hilar cholangiocarcinoma remains largely uncharacterized. In the present study, tissue microarrays containing resected hilar cholangiocarcinoma specimens from 92 patients were used to evaluate the expression of SPARCL1 protein by immunohistochemistry (IHC). In vitro assays were used to determine the effect of SPARCL1 overexpression on cell growth and migration. Loss of SPARCL1 expression was observed in 46 (50.0 %) of the 92 primary tumors. SPARCL1 expression is inversely associated with poorly or undifferentiation specimens (P = 0.030) in addition to lymph node metastasis (P = 0.047). Survival analysis demonstrated that SPARCL1 is an independent factor in predicting the outcome of patients with hilar cholangiocarcinoma. SPARCL1 overexpression suppressed tumor cell migration in vitro by inhibiting MMP-9, MMP-2, Vimentin, and Fibronectin expression, whereas did not inhibit cell proliferation in vitro. Our results suggest that loss of SPARCL1 is involved in the tumorigenesis of hilar cholangiocarcinoma and may serve as a novel molecular biomarker for patients' outcome. STN","prediction_labels":"ANIMAL"},{"cleaned":"combined detection tumor markers diagnosis prognosis gallbladder cancer aim clarify value combined use markers diagnosis gallbladder cancer prediction prognosis methods serum cancer antigens ca 199 ca242 carcinoembryonic antigen cea ca125 levels measured 78 patients gallbladder cancer gbc 78 patients benign gallbladder diseases 78 healthy controls using electrochemiluminescence ca199 ca242 cea ca125 levels positive rates analyzed evaluated pre post operatively receiver operator characteristic curves used determine diagnostic sensitivity specificity gbc survival time analysis including survival curves multivariate survival analysis cox proportional hazards model performed evaluate independent prognostic factors results serum ca242 ca125 ca199 levels gbc group significantly higher compared benign gallbladder disease healthy control groups p 0 01 single tumor marker gbc diagnosis sensitivity ca199 highest 71 7 highest specificity ca242 98 7 diagnostic accuracy highest combination ca199 ca242 ca125 69 2 ca242 regarded tumor marker gbc infiltration early stage sensitivity ca199 ca242 increased progression gbc advanced lymph node metastasis p 0 05 78 gbc patients followed 6 12 mo mean 8 mo time serum ca199 ca125 ca242 levels recurrence group significantly higher patients without recurrence p 0 01 post operative serum ca199 ca125 ca242 levels non recurrence group significantly lower gbc group p 0 01 multivariate survival analysis using cox proportional hazards model showed cancer gallbladder neck ca199 expression level independent prognostic factors conclusion ca242 marker gbc infiltration early stage ca199 cancer gallbladder neck therapeutic prognostic markers pubmed","probabilities":0.9799733,"Title":"Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer","Abstract":"AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA)199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre- and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors. RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non-recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors. CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers.","Source":"PubMed","category":"HUMAN","training_data":"Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer AIM: To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis. METHODS: Serum cancer antigens (CA)199, CA242, carcinoembryonic antigen (CEA), and CA125 levels were measured in 78 patients with gallbladder cancer (GBC), 78 patients with benign gallbladder diseases, and 78 healthy controls using electrochemiluminescence. CA199, CA242, CEA, and CA125 levels and positive rates were analyzed and evaluated pre- and post-operatively. Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC. Survival time analysis, including survival curves, and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors. RESULTS: Serum CA242, CA125, and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups (P < 0.01). With a single tumor marker for GBC diagnosis, the sensitivity of CA199 was the highest (71.7%), with the highest specificity being in CA242 (98.7%). Diagnostic accuracy was highest with a combination of CA199, CA242, and CA125 (69.2%). CA242 could be regarded as a tumor marker of GBC infiltration in the early stage. The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis (P < 0.05). The 78 GBC patients were followed up for 6-12 mo (mean: 8 mo), during which time serum CA199, CA125, and CA242 levels in the recurrence group were significantly higher than in patients without recurrence (P < 0.01). The post-operative serum CA199, CA125, and CA242 levels in the non-recurrence group were significantly lower than those in the GBC group (P < 0.01). Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors. CONCLUSION: CA242 is a marker of GBC infiltration in the early stage. CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"yttrium 90 radioembolization cost effective intrahepatic cholangiocarcinoma seer medicare population study purpose analyze cost effectiveness radioembolization treatment intrahepatic cholangiocarcinoma icc using surveillance epidemiology end results seer medicare cancer database materials methods cost measured total treatment related reimbursement patients diagnosed icc received chemotherapy alone chemotherapy yttrium 90 radioembolization assessed seer medicare cancer database 1999 2012 survival analysis performed incremental cost effectiveness ratios generated results study included 585 patients average age diagnosis 71 years standard deviation 9 9 52 patients male twelve percent patients received chemotherapy radioembolization n 72 88 patients n 513 received chemotherapy median survival 1043 days 95 confidence interval ci 894 1244 chemotherapy plus radioembolization 811 days 95 ci 705 925 chemotherapy alone p 02 patients received combination therapy slightly younger 71 vs 69 years p 03 significant differences observed treatment groups age treatment sex race city size multivariable analysis showed hazard ratio progression combination therapy versus chemotherapy alone 0 76 95 ci 0 59 0 97 p 029 incremental cost effectiveness ratio measure cost added year life 50 058 65 per year quartiles 11 454 63 52 763 28 conclusions combination therapy icc chemotherapy radioembolization associated higher median survival cost effective treatment median cost 50 058 65 per additional year survival pubmed","probabilities":0.9799733,"Title":"Yttrium-90 Radioembolization Is Cost Effective in Intrahepatic Cholangiocarcinoma: A SEER Medicare Population Study","Abstract":"PURPOSE: To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database. MATERIALS AND METHODS: Cost as measured by total treatment-related reimbursement in patients diagnosed with ICC who received chemotherapy alone or chemotherapy and yttrium-90 radioembolization was assessed in the SEER Medicare cancer database (1999-2012). Survival analysis was performed, and incremental cost-effectiveness ratios were generated. RESULTS: The study included 585 patients. Average age at diagnosis was 71 years (standard deviation: 9.9), and 52% of patients were male. Twelve percent of patients received chemotherapy with radioembolization (n = 72), and 88% of patients (n = 513) received only chemotherapy. Median survival was 1043 days (95% confidence interval [CI]: 894-1244) for chemotherapy plus radioembolization and 811 days (95% CI: 705-925) for chemotherapy alone (P = .02). Patients who received combination therapy were slightly younger (71 vs 69 years, P = .03). No significant differences were observed between treatment groups in age at treatment, sex, race, or city size. Multivariable analysis showed a hazard ratio for progression for combination therapy versus chemotherapy alone of 0.76 (95% CI: 0.59-0.97, P = .029). The incremental cost-effectiveness ratio, a measure of cost of each added year of life, was $50,058.65 per year (quartiles: $11,454.63, $52,763.28). CONCLUSIONS: Combination therapy of ICC with chemotherapy and radioembolization is associated with higher median survival and can be a cost-effective treatment, with a median cost of $50,058.65 per additional year of survival.","Source":"PubMed","category":"HUMAN","training_data":"Yttrium-90 Radioembolization Is Cost Effective in Intrahepatic Cholangiocarcinoma: A SEER Medicare Population Study PURPOSE: To analyze the cost-effectiveness of radioembolization in the treatment of intrahepatic cholangiocarcinoma (ICC) using the Surveillance, Epidemiology, and End Results (SEER) Medicare cancer database. MATERIALS AND METHODS: Cost as measured by total treatment-related reimbursement in patients diagnosed with ICC who received chemotherapy alone or chemotherapy and yttrium-90 radioembolization was assessed in the SEER Medicare cancer database (1999-2012). Survival analysis was performed, and incremental cost-effectiveness ratios were generated. RESULTS: The study included 585 patients. Average age at diagnosis was 71 years (standard deviation: 9.9), and 52% of patients were male. Twelve percent of patients received chemotherapy with radioembolization (n = 72), and 88% of patients (n = 513) received only chemotherapy. Median survival was 1043 days (95% confidence interval [CI]: 894-1244) for chemotherapy plus radioembolization and 811 days (95% CI: 705-925) for chemotherapy alone (P = .02). Patients who received combination therapy were slightly younger (71 vs 69 years, P = .03). No significant differences were observed between treatment groups in age at treatment, sex, race, or city size. Multivariable analysis showed a hazard ratio for progression for combination therapy versus chemotherapy alone of 0.76 (95% CI: 0.59-0.97, P = .029). The incremental cost-effectiveness ratio, a measure of cost of each added year of life, was $50,058.65 per year (quartiles: $11,454.63, $52,763.28). CONCLUSIONS: Combination therapy of ICC with chemotherapy and radioembolization is associated with higher median survival and can be a cost-effective treatment, with a median cost of $50,058.65 per additional year of survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prima 1 met induces cellular senescence apoptotic cell death cholangiocarcinoma cells background aim study examined vitro effects bile duct cancer drug prima 1met cholangiocarcinoma cca cell growth determine potential usefulness cca therapy materials methods effect drug expression senescent markers p16ink4a p21 phosphorylation p53 investigated association senescent markers patients clinicopathological data results prima 1met inhibited cca cell growth half maximal inhibitory concentration ic50 values 21 9 40 8 m prima 1met induced phospho p53 p16ink4a p21 triggering cellular senescence apoptosis high expressions p16ink4a p21 associated high survival rate patients cca conclusion prima 1met may potentially alternative anticancer agent might lead better prognosis patients cca stn","probabilities":0.9467213,"Title":"Prima-1(Met) Induces Cellular Senescence And Apoptotic Cell Death In Cholangiocarcinoma Cells","Abstract":"Background/aim: This study examined the in vitro effects of the bile duct cancer drug PRIMA-1MET on cholangiocarcinoma (CCA) cell growth to determine its potential usefulness in CCA therapy. \r\n\r\n Materials and methods: The effect of this drug on the expression of senescent markers (p16INK4A and p21) and the phosphorylation of p53 was investigated, as was the association between senescent markers and the patients' clinicopathological data. \r\n\r\n Results: PRIMA-1MET inhibited CCA cell growth with the half maximal-inhibitory concentration (IC50) values of 21.9-40.8 μM. PRIMA-1MET induced phospho-p53, p16INK4A and p21 triggering cellular senescence and apoptosis. High expressions of p16INK4A and p21 were associated with a high survival rate of patients with CCA. \r\n\r\n Conclusion: PRIMA-1MET may potentially be an alternative anticancer agent that might lead to a better prognosis in patients with CCA.","Source":"STN","category":"ANIMAL","training_data":"Prima-1(Met) Induces Cellular Senescence And Apoptotic Cell Death In Cholangiocarcinoma Cells Background/aim: This study examined the in vitro effects of the bile duct cancer drug PRIMA-1MET on cholangiocarcinoma (CCA) cell growth to determine its potential usefulness in CCA therapy. \r\n\r\n Materials and methods: The effect of this drug on the expression of senescent markers (p16INK4A and p21) and the phosphorylation of p53 was investigated, as was the association between senescent markers and the patients' clinicopathological data. \r\n\r\n Results: PRIMA-1MET inhibited CCA cell growth with the half maximal-inhibitory concentration (IC50) values of 21.9-40.8 μM. PRIMA-1MET induced phospho-p53, p16INK4A and p21 triggering cellular senescence and apoptosis. High expressions of p16INK4A and p21 were associated with a high survival rate of patients with CCA. \r\n\r\n Conclusion: PRIMA-1MET may potentially be an alternative anticancer agent that might lead to a better prognosis in patients with CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"expression prognostic significance cancer testis antigens cta intrahepatic cholagiocarcinoma background cancer testis antigens ctas suitable targets cancer specific immunotherapy aim study investigate expression ctas intrahepatic cholagiocarcinoma ihcc evaluate potential therapeutic values methods eighty nine ihcc patients retrospectively assessed expression ctas hla class immunohistochemistry using following antibodies ma454 recognizing mage a1 57b recognizing multiple mage mage a3 a4 e978 recognizing ny eso 1 emr8 5 recognizing hla class clinicopathological prognostic significance individual cta markers combination evaluated results expression rates mage a1 mage a3 4 ny eso 1 29 2 27 0 22 5 respectively concomitant expression ctas hla class antigen observed 33 7 ihcc tumors found positive mage 3 4 expression correlated larger tumor size 5 cm tumor recurrence poor prognosis moreover identified 52 cases 58 4 ihcc patients least one cta marker expression subgroup displayed higher frequency larger tumor size shorter survival cases furthermore expression least one cta marker also independent prognostic factor patients ihcc conclusion data suggest specific immunotherapy targeted ctas might novel treatment option ihcc patients pubmed","probabilities":0.9799733,"Title":"Expression and prognostic significance of cancer-testis antigens (CTA) in intrahepatic cholagiocarcinoma","Abstract":"BACKGROUND: Cancer-testis antigens (CTAs) are suitable targets for cancer-specific immunotherapy. The aim of the study is to investigate the expression of CTAs in intrahepatic cholagiocarcinoma (IHCC) and evaluate their potential therapeutic values. METHODS: Eighty-nine IHCC patients were retrospectively assessed for their expression of CTAs and HLA Class I by immunohistochemistry using the following antibodies: MA454 recognizing MAGE-A1, 57B recognizing multiple MAGE-A (MAGE-A3/A4), E978 recognizing NY-ESO-1, and EMR8-5 recognizing HLA class I. The clinicopathological and prognostic significance of individual CTA markers and their combination were further evaluated. RESULTS: The expression rates of MAGE-A1, MAGE-A3/4 and NY-ESO-1 were 29.2%, 27.0% and 22.5%, respectively. The concomitant expression of CTAs and HLA class I antigen was observed in 33.7% of the IHCC tumors. We found that positive MAGE-3/4 expression correlated with larger tumor size (≥ 5 cm), tumor recurrence and poor prognosis. Moreover, we identified 52 cases (58.4%) of IHCC patients with at least one CTA marker expression, and this subgroup displayed a higher frequency of larger tumor size and a shorter survival than the other cases. Furthermore, expression of at least one CTA marker was also an independent prognostic factor in patients with IHCC. CONCLUSION: Our data suggest that specific immunotherapy targeted CTAs might be a novel treatment option for IHCC patients.","Source":"PubMed","category":"HUMAN","training_data":"Expression and prognostic significance of cancer-testis antigens (CTA) in intrahepatic cholagiocarcinoma BACKGROUND: Cancer-testis antigens (CTAs) are suitable targets for cancer-specific immunotherapy. The aim of the study is to investigate the expression of CTAs in intrahepatic cholagiocarcinoma (IHCC) and evaluate their potential therapeutic values. METHODS: Eighty-nine IHCC patients were retrospectively assessed for their expression of CTAs and HLA Class I by immunohistochemistry using the following antibodies: MA454 recognizing MAGE-A1, 57B recognizing multiple MAGE-A (MAGE-A3/A4), E978 recognizing NY-ESO-1, and EMR8-5 recognizing HLA class I. The clinicopathological and prognostic significance of individual CTA markers and their combination were further evaluated. RESULTS: The expression rates of MAGE-A1, MAGE-A3/4 and NY-ESO-1 were 29.2%, 27.0% and 22.5%, respectively. The concomitant expression of CTAs and HLA class I antigen was observed in 33.7% of the IHCC tumors. We found that positive MAGE-3/4 expression correlated with larger tumor size (≥ 5 cm), tumor recurrence and poor prognosis. Moreover, we identified 52 cases (58.4%) of IHCC patients with at least one CTA marker expression, and this subgroup displayed a higher frequency of larger tumor size and a shorter survival than the other cases. Furthermore, expression of at least one CTA marker was also an independent prognostic factor in patients with IHCC. CONCLUSION: Our data suggest that specific immunotherapy targeted CTAs might be a novel treatment option for IHCC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact preoperative endoscopic cholangiography biliary drainage ampulla vater cancer background ampulla vater aov carcinoma rare malignancy relatively good prognosis aims study determine clinicopathologic factors associated survival disease recurrence patients aov cancer focusing impact preoperative endoscopic retrograde cholangiopancreatography ercp type biliary drainage endoscopic retrograde biliary drainage erbd percutaneous transhepatic biliary drainage ptbd methods retrospectively reviewed medical records 80 patients underwent curative resection aov cancer single institution 1995 2015 clinicopathologic factors associated survival disease recurrence analyzed using univariate multivariable tests results 5 year disease free overall actuarial survival rates 39 3 51 3 respectively moderate poor differentiation preoperative ercp advanced stage lymph node metastases advanced stage lymphovascular invasion associated disease free survival univariate analyses prognosis worse patients underwent erbd patients underwent ptbd biliary drainage multivariable analysis showed advanced ajcc stage preoperative ercp independent risk factors recurrence patient underwent preoperative ercp significantly higher rate early distant metastasis within 1 year especially patients early stage aov cancer conclusions preoperative ercp independent risk factor postoperative recurrence patients aov cancer characterized early distant metastasis early stage cancer therefore unnecessary ercp avoided patients aov cancer biliary drainage necessary ptbd may preferred erbd aov cancer pubmed","probabilities":0.9799733,"Title":"Impact of preoperative endoscopic cholangiography and biliary drainage in Ampulla of Vater cancer","Abstract":"BACKGROUND: Ampulla of Vater (AOV) carcinoma is a rare malignancy but has a relatively good prognosis. The aims of this study were to determine the clinicopathologic factors associated with survival and disease recurrence in patients with AOV cancer, focusing on the impact of preoperative endoscopic retrograde cholangiopancreatography (ERCP) and type of biliary drainage (endoscopic retrograde biliary drainage [ERBD] or percutaneous transhepatic biliary drainage [PTBD]). METHODS: We retrospectively reviewed the medical records of 80 patients who underwent curative resection for AOV cancer at a single institution between 1995 and 2015. The clinicopathologic factors associated with survival and disease recurrence were analyzed using univariate and multivariable tests. RESULTS: The 5-year disease-free and overall actuarial survival rates were 39.3% and 51.3%, respectively. Moderate or poor differentiation, preoperative ERCP, advanced T stage, lymph node metastases, advanced stage and lymphovascular invasion were associated with disease-free survival in univariate analyses. The prognosis was worse in patients who underwent ERBD than in patients who underwent PTBD or no biliary drainage. Multivariable analysis showed that advanced AJCC stage and preoperative ERCP were independent risk factors for recurrence. Patient who underwent preoperative ERCP had a significantly higher rate of early distant metastasis within 1 year, especially in patients with early stage AOV cancer. CONCLUSIONS: Preoperative ERCP was an independent risk factor for postoperative recurrence in patients with AOV cancer, and is characterized by early distant metastasis in early stage cancer. Therefore, unnecessary ERCP should be avoided in patients with AOV cancer. If biliary drainage is necessary, PTBD may be preferred to ERBD in AOV cancer.","Source":"PubMed","category":"HUMAN","training_data":"Impact of preoperative endoscopic cholangiography and biliary drainage in Ampulla of Vater cancer BACKGROUND: Ampulla of Vater (AOV) carcinoma is a rare malignancy but has a relatively good prognosis. The aims of this study were to determine the clinicopathologic factors associated with survival and disease recurrence in patients with AOV cancer, focusing on the impact of preoperative endoscopic retrograde cholangiopancreatography (ERCP) and type of biliary drainage (endoscopic retrograde biliary drainage [ERBD] or percutaneous transhepatic biliary drainage [PTBD]). METHODS: We retrospectively reviewed the medical records of 80 patients who underwent curative resection for AOV cancer at a single institution between 1995 and 2015. The clinicopathologic factors associated with survival and disease recurrence were analyzed using univariate and multivariable tests. RESULTS: The 5-year disease-free and overall actuarial survival rates were 39.3% and 51.3%, respectively. Moderate or poor differentiation, preoperative ERCP, advanced T stage, lymph node metastases, advanced stage and lymphovascular invasion were associated with disease-free survival in univariate analyses. The prognosis was worse in patients who underwent ERBD than in patients who underwent PTBD or no biliary drainage. Multivariable analysis showed that advanced AJCC stage and preoperative ERCP were independent risk factors for recurrence. Patient who underwent preoperative ERCP had a significantly higher rate of early distant metastasis within 1 year, especially in patients with early stage AOV cancer. CONCLUSIONS: Preoperative ERCP was an independent risk factor for postoperative recurrence in patients with AOV cancer, and is characterized by early distant metastasis in early stage cancer. Therefore, unnecessary ERCP should be avoided in patients with AOV cancer. If biliary drainage is necessary, PTBD may be preferred to ERBD in AOV cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"new genomic landscapes therapeutic targets biliary tract cancers biliary tract cancers btcs heterogeneous group neoplasms characterized dismal prognosis variance solid tumors effective molecular targeted agent currently approved btcs treatment molecular landscape recently investigated comprehensive mutational profiling studies identified idh1 2 bap1 characteristic intrahepatic cholangiocarcinomas extrahepatic cholangiocarcinomas gallbladder carcinomas characterized frequent kras tp53 alterations moreover targeted next generation sequencing uncovered alterations several key cellular pathways btc specific alterations include disorders major regulators cell cycle chromatin remodeling processes well deregulation mtor tgf beta smad receptor tyrosine kinases signaling next step correlation findings clinical trials identify predictive biomarkers development personalized therapies permit early access btc patients innovative drugs pubmed","probabilities":0.962963,"Title":"New genomic landscapes and therapeutic targets for biliary tract cancers","Abstract":"Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms characterized by a dismal prognosis. At variance with most solid tumors, no effective molecular targeted agent has been currently approved for BTCs treatment and their molecular landscape has only been recently investigated. Comprehensive mutational profiling studies identified IDH1/2 and BAP1 as characteristic of intrahepatic cholangiocarcinomas, while extrahepatic cholangiocarcinomas and gallbladder carcinomas were characterized by frequent KRAS and TP53 alterations. Moreover, targeted next-generation sequencing has uncovered alterations in several key cellular pathways. BTC-specific alterations include disorders of major regulators of cell cycle and chromatin remodeling processes, as well as deregulation of the mTOR-, TGF-beta/Smad- and receptor tyrosine kinases signaling. The next step will be the correlation of these findings with clinical trials to identify predictive biomarkers for the development of personalized therapies. This will permit early access for BTC patients to innovative drugs.","Source":"PubMed","category":"HUMAN","training_data":"New genomic landscapes and therapeutic targets for biliary tract cancers Biliary tract cancers (BTCs) are a heterogeneous group of neoplasms characterized by a dismal prognosis. At variance with most solid tumors, no effective molecular targeted agent has been currently approved for BTCs treatment and their molecular landscape has only been recently investigated. Comprehensive mutational profiling studies identified IDH1/2 and BAP1 as characteristic of intrahepatic cholangiocarcinomas, while extrahepatic cholangiocarcinomas and gallbladder carcinomas were characterized by frequent KRAS and TP53 alterations. Moreover, targeted next-generation sequencing has uncovered alterations in several key cellular pathways. BTC-specific alterations include disorders of major regulators of cell cycle and chromatin remodeling processes, as well as deregulation of the mTOR-, TGF-beta/Smad- and receptor tyrosine kinases signaling. The next step will be the correlation of these findings with clinical trials to identify predictive biomarkers for the development of personalized therapies. This will permit early access for BTC patients to innovative drugs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"predictors postoperative early recurrence extrahepatic bile duct cancer purposes resected bile duct cancers often relapse postoperative follow aim study detect predictors early recurrence patients extrahepatic bile duct cancer methods consecutive cases n 162 extrahepatic bile duct cancer r0 r1 resection achieved kobe university hospital 2000 2016 divided three groups early recurrence er within 6 months surgery late recurrence lr recurrence nr clinicopathological features compared results twenty two patients 14 developed er 69 43 developed lr surgery rates lymph node metastasis residual cancer status similar three groups liver metastasis common er group lr group 59 vs 32 p 0 02 er significantly worse prognosis lr nr 7 vs 44 vs 85 1 year p 0 01 respectively multivariate analysis showed age 75 years serum ca19 9 1008 u ml perineural invasion independent predictors early recurrence conclusions high serum ca19 9 values 1008 u ml independent predictor early recurrence neoadjuvant therapy aggressive adjuvant therapy may beneficial patients show highly elevated ca19 9 values surgery stn","probabilities":0.9799733,"Title":"Predictors Of Postoperative Early Recurrence Of Extrahepatic Bile Duct Cancer","Abstract":"Purposes: Resected bile duct cancers often relapse during postoperative follow-up. The aim of this study was to detect predictors of early recurrence in patients with extrahepatic bile duct cancer. \n\n Methods: Consecutive cases (n = 162) of extrahepatic bile duct cancer in which R0 or R1 resection was achieved in Kobe University Hospital between 2000 and 2016 were divided into three groups [early recurrence (ER), within 6 months of surgery, late recurrence (LR), and no recurrence (NR)] and their clinicopathological features were compared. \n\n Results: Twenty-two patients (14%) developed ER and 69 (43%) developed LR after surgery. The rates of lymph node metastasis and residual cancer status were similar in all three groups. Liver metastasis was more common in the ER group than in the LR group (59% vs. 32%, p = 0.02). ER had a significantly worse prognosis than LR and NR (7% vs. 44% vs. 85% at 1 year, p < 0.01, respectively). Multivariate analysis showed that age > 75 years, serum CA19-9 > 1008 U/ml and perineural invasion were independent predictors of early recurrence. \n\n Conclusions: High serum CA19-9 values (> 1008 U/ml) were an independent predictor of early recurrence. Neoadjuvant therapy and aggressive adjuvant therapy may be beneficial for patients who show highly elevated CA19-9 values before surgery.","Source":"STN","category":"HUMAN","training_data":"Predictors Of Postoperative Early Recurrence Of Extrahepatic Bile Duct Cancer Purposes: Resected bile duct cancers often relapse during postoperative follow-up. The aim of this study was to detect predictors of early recurrence in patients with extrahepatic bile duct cancer. \n\n Methods: Consecutive cases (n = 162) of extrahepatic bile duct cancer in which R0 or R1 resection was achieved in Kobe University Hospital between 2000 and 2016 were divided into three groups [early recurrence (ER), within 6 months of surgery, late recurrence (LR), and no recurrence (NR)] and their clinicopathological features were compared. \n\n Results: Twenty-two patients (14%) developed ER and 69 (43%) developed LR after surgery. The rates of lymph node metastasis and residual cancer status were similar in all three groups. Liver metastasis was more common in the ER group than in the LR group (59% vs. 32%, p = 0.02). ER had a significantly worse prognosis than LR and NR (7% vs. 44% vs. 85% at 1 year, p < 0.01, respectively). Multivariate analysis showed that age > 75 years, serum CA19-9 > 1008 U/ml and perineural invasion were independent predictors of early recurrence. \n\n Conclusions: High serum CA19-9 values (> 1008 U/ml) were an independent predictor of early recurrence. Neoadjuvant therapy and aggressive adjuvant therapy may be beneficial for patients who show highly elevated CA19-9 values before surgery. STN","prediction_labels":"HUMAN"},{"cleaned":"trends gallbladder cancer jordan 2 decades background study aims prevalence gallbladder cancer gbc varies different parts world study review literature update previously published study conducted university aims reassess incidence gbc past 2 decades patients methods conducted retrospective study 2002 2016 data regarding demographics clinical presentation risk factors histopathology investigations treatments obtained diagnosis gbc established surgery primarily detected surgical specimen classified incidental results 11 391 cholecystectomies performed 31 cases 0 27 gbc found mean age patients gbc 68 years 43 103 years 74 women annual incidence gbc 0 2 100 000 men 0 1 100 000 women 0 3 100 000 biliary colic acute cholecystitis main presentations diagnosis gbc incidental 67 cases 75 patients gbc gallstones 13 polyps 3 porcelain gallbladder adenocarcinoma dominant 87 histologic type conclusions gbc rate region similar others parts world still low changed past 2 decades study consolidates previously published recommendations regarding high index suspicion gbc elderly cholelithiasis stn","probabilities":0.9799733,"Title":"Trends Of Gallbladder Cancer In Jordan Over 2 Decades: Where Are We?","Abstract":"Background and study aims: The prevalence of gallbladder cancer (GBC) varies between different parts of the world. This study is a review of literature and an update of a previously published study conducted in our university and aims to reassess the incidence of GBC over the past 2 decades. \r\n\r\n Patients and methods: We conducted a retrospective study between 2002 and 2016. Data regarding demographics, clinical presentation, risk factors, histopathology, investigations, and treatments were obtained. A diagnosis of GBC established during surgery or primarily detected in the surgical specimen was classified as incidental. \r\n\r\n Results: Of 11 391 cholecystectomies performed, 31 cases (0.27%) of GBC were found. The mean age of patients with GBC was 68 years (43-103 years), 74% were women. The annual incidence of GBC was 0.2/100 000 (men: 0.1/100 000; women: 0.3/100 000). Biliary colic and acute cholecystitis were the main presentations. Diagnosis of GBC was \"incidental\" in 67% of cases. About 75% of patients with GBC had gallstones, 13% had polyps, and 3% had porcelain gallbladder. Adenocarcinoma was the dominant (87%) histologic type. \r\n\r\n Conclusions: The GBC rate in our region, similar to others parts of the world, is still low and has not changed over the past 2 decades. This study consolidates the previously published recommendations regarding the high index of suspicion of GBC in elderly with cholelithiasis.","Source":"STN","category":"HUMAN","training_data":"Trends Of Gallbladder Cancer In Jordan Over 2 Decades: Where Are We? Background and study aims: The prevalence of gallbladder cancer (GBC) varies between different parts of the world. This study is a review of literature and an update of a previously published study conducted in our university and aims to reassess the incidence of GBC over the past 2 decades. \r\n\r\n Patients and methods: We conducted a retrospective study between 2002 and 2016. Data regarding demographics, clinical presentation, risk factors, histopathology, investigations, and treatments were obtained. A diagnosis of GBC established during surgery or primarily detected in the surgical specimen was classified as incidental. \r\n\r\n Results: Of 11 391 cholecystectomies performed, 31 cases (0.27%) of GBC were found. The mean age of patients with GBC was 68 years (43-103 years), 74% were women. The annual incidence of GBC was 0.2/100 000 (men: 0.1/100 000; women: 0.3/100 000). Biliary colic and acute cholecystitis were the main presentations. Diagnosis of GBC was \"incidental\" in 67% of cases. About 75% of patients with GBC had gallstones, 13% had polyps, and 3% had porcelain gallbladder. Adenocarcinoma was the dominant (87%) histologic type. \r\n\r\n Conclusions: The GBC rate in our region, similar to others parts of the world, is still low and has not changed over the past 2 decades. This study consolidates the previously published recommendations regarding the high index of suspicion of GBC in elderly with cholelithiasis. STN","prediction_labels":"HUMAN"},{"cleaned":"cytological features hepatoid adenocarcinoma gallbladder case report immunocytochemical analyzes hepatoid adenocarcinoma defined extrahepatic malignant neoplasm showing morphological immunohistochemical resemblance hepatocellular carcinoma occurrence type tumor gallbladder extremely rare study report first cytological case hepatoid adenocarcinoma gallbladder 80 year old japanese female found tumorous lesion gallbladder papanicolaou smear ascites demonstrated epithelial cell clusters composed round oval neoplastic cells distinct cell border large centrally located nuclei tumor touch smear resected tumor revealed presence two distinct neoplastic components first component composed clusters sheets epithelial cells distinct cell border relatively rich clear cytoplasm centrally located nuclei seen ascites specimen component composed tall columnar cells large basally oriented nuclei glandular formation noted well immunocytochemical analyzes touch smear material demonstrated former component positive heppar1 thus considered hepatoid adenocarcinoma latter component deemed typical adenocarcinoma histopathological immunohistochemical examination resected gallbladder tumor confirmed diagnosis hepatoid adenocarcinoma characteristic cytological features hepatoid adenocarcinoma presence sheets clusters neoplastic cells distinct cell border centrally located nuclei immunocytochemical analysis heppar1 may help diagnosis demonstration hepatoid adenocarcinoma important cytological specimen type tumor shows aggressive clinical course stn","probabilities":0.9467213,"Title":"Cytological Features Of Hepatoid Adenocarcinoma Of The Gallbladder: A Case Report With Immunocytochemical Analyzes","Abstract":"Hepatoid adenocarcinoma is defined as an extrahepatic malignant neoplasm showing morphological and immunohistochemical resemblance of hepatocellular carcinoma. The occurrence of this type of tumor in the gallbladder is extremely rare. In this study, we report the first cytological case of hepatoid adenocarcinoma of the gallbladder. An 80-year-old Japanese female was found to have a tumorous lesion in the gallbladder. Papanicolaou smear of the ascites demonstrated a few epithelial cell clusters composed of round to oval neoplastic cells with distinct cell border and large centrally-located nuclei. Tumor touch smear of the resected tumor revealed the presence of two distinct neoplastic components. The first component was composed of clusters or sheets of epithelial cells with distinct cell border, relatively rich clear cytoplasm, and centrally-located nuclei, as seen in the ascites specimen. The other component was composed of tall columnar cells with large basally-oriented nuclei, and glandular formation was noted as well. Immunocytochemical analyzes of the touch smear material demonstrated that the former component was positive for HepPar1, thus it was considered as a hepatoid adenocarcinoma, and the latter component deemed as a typical adenocarcinoma. Histopathological and immunohistochemical examination of the resected gallbladder tumor confirmed a diagnosis of hepatoid adenocarcinoma. The characteristic cytological features of hepatoid adenocarcinoma are the presence of sheets or clusters of neoplastic cells with distinct cell border and centrally-located nuclei. Immunocytochemical analysis for HepPar1 may help its diagnosis. Demonstration of hepatoid adenocarcinoma is important in the cytological specimen because this type of tumor shows an aggressive clinical course.","Source":"STN","category":"ANIMAL","training_data":"Cytological Features Of Hepatoid Adenocarcinoma Of The Gallbladder: A Case Report With Immunocytochemical Analyzes Hepatoid adenocarcinoma is defined as an extrahepatic malignant neoplasm showing morphological and immunohistochemical resemblance of hepatocellular carcinoma. The occurrence of this type of tumor in the gallbladder is extremely rare. In this study, we report the first cytological case of hepatoid adenocarcinoma of the gallbladder. An 80-year-old Japanese female was found to have a tumorous lesion in the gallbladder. Papanicolaou smear of the ascites demonstrated a few epithelial cell clusters composed of round to oval neoplastic cells with distinct cell border and large centrally-located nuclei. Tumor touch smear of the resected tumor revealed the presence of two distinct neoplastic components. The first component was composed of clusters or sheets of epithelial cells with distinct cell border, relatively rich clear cytoplasm, and centrally-located nuclei, as seen in the ascites specimen. The other component was composed of tall columnar cells with large basally-oriented nuclei, and glandular formation was noted as well. Immunocytochemical analyzes of the touch smear material demonstrated that the former component was positive for HepPar1, thus it was considered as a hepatoid adenocarcinoma, and the latter component deemed as a typical adenocarcinoma. Histopathological and immunohistochemical examination of the resected gallbladder tumor confirmed a diagnosis of hepatoid adenocarcinoma. The characteristic cytological features of hepatoid adenocarcinoma are the presence of sheets or clusters of neoplastic cells with distinct cell border and centrally-located nuclei. Immunocytochemical analysis for HepPar1 may help its diagnosis. Demonstration of hepatoid adenocarcinoma is important in the cytological specimen because this type of tumor shows an aggressive clinical course. STN","prediction_labels":"ANIMAL"},{"cleaned":"portal vein embolization extended hepatectomy biliary cancer current technique review 494 consecutive embolizations backgrounds portal vein embolization pve widely applied extended hepatectomy however clinical utility patients biliary cancer fully addressed methods 1991 2010 494 patients cholangiocarcinoma n 353 gallbladder cancer n 141 underwent pve extended hepatectomy pve performed transhepatic ipsilateral approach using fibrin glue absolute ethanol steel coils surgical outcomes cohort retrospectively reviewed results pve related complications requiring interventions found 3 0 6 494 patients patient died complications among 494 patients 122 24 7 undergo subsequent hepatectomy unresectability rate significantly higher patients gallbladder cancer cholangiocarcinoma 43 2 61 141 17 3 61 353 respectively p 0 001 remaining 372 patients underwent hepatectomy 24 6 5 died postoperative complications 13 80 16 3 gallbladder cancer vs 11 292 3 8 cholangiocarcinoma p 0 05 overall survival patients cholangiocarcinoma significantly better patients gallbladder cancer 5 year survival rate 39 23 respectively p 0 001 thirty six patients cholangiocarcinoma 10 patients gallbladder cancer survived 5 years extended surgery conclusion pve performed safely patients cholestatic liver potential benefit patients advanced biliary cancer undergo extended difficult hepatectomy pubmed","probabilities":0.9799733,"Title":"Portal vein embolization before extended hepatectomy for biliary cancer: current technique and review of 494 consecutive embolizations","Abstract":"BACKGROUNDS: Portal vein embolization (PVE) has been widely applied before extended hepatectomy; however, its clinical utility for patients with biliary cancer has not been fully addressed. METHODS: Between 1991 and 2010, 494 patients with cholangiocarcinoma (n = 353) or gallbladder cancer (n = 141) underwent PVE before extended hepatectomy. PVE was performed by a transhepatic ipsilateral approach using fibrin glue or absolute ethanol with steel coils. Surgical outcomes of this cohort were retrospectively reviewed. RESULTS: PVE-related complications requiring interventions were found in 3 (0.6%) of the 494 patients; no patient died of these complications. Among the 494 patients, 122 (24.7%) did not undergo subsequent hepatectomy. The unresectability rate was significantly higher in patients with gallbladder cancer than in those with cholangiocarcinoma [43.2% (61/141) and 17.3% (61/353), respectively, p < 0.001]. The remaining 372 patients underwent hepatectomy, and 24 (6.5%) died of postoperative complications [13 of 80 (16.3%) with gallbladder cancer vs. 11 of 292 (3.8%) with cholangiocarcinoma, p < 0.05]. The overall survival for patients with cholangiocarcinoma was significantly better than that for patients with gallbladder cancer, where the 5-year survival rate was 39 and 23%, respectively (p < 0.001). Thirty-six patients with cholangiocarcinoma and 10 patients with gallbladder cancer survived more than 5 years after extended surgery. CONCLUSION: PVE can be performed safely in patients with cholestatic liver, and it has a potential benefit for patients with advanced biliary cancer who are to undergo extended, difficult hepatectomy.","Source":"PubMed","category":"HUMAN","training_data":"Portal vein embolization before extended hepatectomy for biliary cancer: current technique and review of 494 consecutive embolizations BACKGROUNDS: Portal vein embolization (PVE) has been widely applied before extended hepatectomy; however, its clinical utility for patients with biliary cancer has not been fully addressed. METHODS: Between 1991 and 2010, 494 patients with cholangiocarcinoma (n = 353) or gallbladder cancer (n = 141) underwent PVE before extended hepatectomy. PVE was performed by a transhepatic ipsilateral approach using fibrin glue or absolute ethanol with steel coils. Surgical outcomes of this cohort were retrospectively reviewed. RESULTS: PVE-related complications requiring interventions were found in 3 (0.6%) of the 494 patients; no patient died of these complications. Among the 494 patients, 122 (24.7%) did not undergo subsequent hepatectomy. The unresectability rate was significantly higher in patients with gallbladder cancer than in those with cholangiocarcinoma [43.2% (61/141) and 17.3% (61/353), respectively, p < 0.001]. The remaining 372 patients underwent hepatectomy, and 24 (6.5%) died of postoperative complications [13 of 80 (16.3%) with gallbladder cancer vs. 11 of 292 (3.8%) with cholangiocarcinoma, p < 0.05]. The overall survival for patients with cholangiocarcinoma was significantly better than that for patients with gallbladder cancer, where the 5-year survival rate was 39 and 23%, respectively (p < 0.001). Thirty-six patients with cholangiocarcinoma and 10 patients with gallbladder cancer survived more than 5 years after extended surgery. CONCLUSION: PVE can be performed safely in patients with cholestatic liver, and it has a potential benefit for patients with advanced biliary cancer who are to undergo extended, difficult hepatectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"identification pan gamma secretase inhibitor response signature notch driven cholangiocarcinoma cholangiocarcinoma cca mortality rates increasing result rising incidence limited curative treatment patients advanced disease notch pathway reactivation reported biliary malignancies conflicting degrees hindering prioritization key therapeutic targets within network identification candidate responder patients notch directed therapies analyzed genomic data 341 patients cca identified notch1 significantly increased subgroup characterized distinct stromal infiltration network wide imbalance notch pathway seen cca including correlation notch1 notch3 notch ligands given diversity observed notch receptor engagement secretase modulation rationalized therapeutic option indeed subcutaneous transplantation sensitive resistant cca cell lines pretreated secretase inhibitor gsi cocktail demonstrated antineoplastic effects gsi subset cca led development 225 gene responder signature signature validated independent cohort 119 patients signature enriched liver tumors initiated hydrodynamic injections activated notch compared akt ras driven tumors candidate gsi responder patients characterized distinct transcriptomes overlapping previous hepatobiliary metastasis stemness unique stromal properties dysfunctional intratumoral immune infiltration pan cancer analysis identified 41 9 cancer types harbor prospective gsi responder patients adapted 20 gene gsi sensitivity score metric capable discriminating nanomolar versus micromolar sensitivity cell permeable gsi z llnle cho across 60 diverse tumor lines area curve 1 conclusion established gsi responder signature evidence across several patient cohorts well vitro vivo models enable precision medicine application notch directed therapy cca well prospectively across diverse malignancies stn","probabilities":0.9467213,"Title":"Identification Of A Pan-Gamma-Secretase Inhibitor Response Signature For Notch-Driven Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) mortality rates are increasing as a result of rising incidence and limited curative treatment(s) for patients with advanced disease. NOTCH pathway reactivation has been reported in biliary malignancies to conflicting degrees, hindering prioritization of key therapeutic targets within the network and identification of candidate responder patients for NOTCH-directed therapies. We analyzed genomic data from 341 patients with CCA and identified NOTCH1 significantly increased in a subgroup characterized by distinct stromal infiltration. Network-wide imbalance of the NOTCH pathway was seen in CCA, including correlation of NOTCH1 with NOTCH3 and NOTCH ligands. Given the diversity of observed NOTCH receptor engagement, γ-secretase modulation was rationalized as a therapeutic option. Indeed, subcutaneous transplantation of sensitive and resistant CCA cell lines pretreated with a γ-secretase inhibitor (GSi) cocktail demonstrated the antineoplastic effects of GSi in a subset of CCA and led to the development of a 225-gene responder signature. This signature was validated in an independent cohort of 119 patients. Further, this signature was enriched in liver tumors initiated by hydrodynamic injections of activated-NOTCH as compared with the AKT-RAS-driven tumors. Candidate GSi-responder patients were characterized by distinct transcriptomes overlapping with previous hepatobiliary metastasis and stemness, unique stromal properties, and dysfunctional intratumoral immune infiltration. Pan-cancer analysis identified 41.9% of cancer types to harbor prospective GSi-responder patients, which was adapted into a 20-gene GSi-sensitivity score metric capable of discriminating nanomolar versus micromolar sensitivity to a cell-permeable GSi (Z-LLNle-CHO) across 60 diverse tumor lines (area under the curve = 1). Conclusion: We have established a GSi-responder signature with evidence across several patient cohorts, as well as in vitro and in vivo models, to enable precision medicine application of NOTCH-directed therapy in CCA as well as prospectively across diverse malignancies.","Source":"STN","category":"ANIMAL","training_data":"Identification Of A Pan-Gamma-Secretase Inhibitor Response Signature For Notch-Driven Cholangiocarcinoma Cholangiocarcinoma (CCA) mortality rates are increasing as a result of rising incidence and limited curative treatment(s) for patients with advanced disease. NOTCH pathway reactivation has been reported in biliary malignancies to conflicting degrees, hindering prioritization of key therapeutic targets within the network and identification of candidate responder patients for NOTCH-directed therapies. We analyzed genomic data from 341 patients with CCA and identified NOTCH1 significantly increased in a subgroup characterized by distinct stromal infiltration. Network-wide imbalance of the NOTCH pathway was seen in CCA, including correlation of NOTCH1 with NOTCH3 and NOTCH ligands. Given the diversity of observed NOTCH receptor engagement, γ-secretase modulation was rationalized as a therapeutic option. Indeed, subcutaneous transplantation of sensitive and resistant CCA cell lines pretreated with a γ-secretase inhibitor (GSi) cocktail demonstrated the antineoplastic effects of GSi in a subset of CCA and led to the development of a 225-gene responder signature. This signature was validated in an independent cohort of 119 patients. Further, this signature was enriched in liver tumors initiated by hydrodynamic injections of activated-NOTCH as compared with the AKT-RAS-driven tumors. Candidate GSi-responder patients were characterized by distinct transcriptomes overlapping with previous hepatobiliary metastasis and stemness, unique stromal properties, and dysfunctional intratumoral immune infiltration. Pan-cancer analysis identified 41.9% of cancer types to harbor prospective GSi-responder patients, which was adapted into a 20-gene GSi-sensitivity score metric capable of discriminating nanomolar versus micromolar sensitivity to a cell-permeable GSi (Z-LLNle-CHO) across 60 diverse tumor lines (area under the curve = 1). Conclusion: We have established a GSi-responder signature with evidence across several patient cohorts, as well as in vitro and in vivo models, to enable precision medicine application of NOTCH-directed therapy in CCA as well as prospectively across diverse malignancies. STN","prediction_labels":"ANIMAL"},{"cleaned":"initial performance profile new 6f self expanding metal stent palliation malignant hilar biliary obstruction background 6f endoscopic biliary self expanding metal stent sems newly introduced intended simultaneous side side bilateral deployment hilar malignant obstruction objective report initial experience zilver 635 biliary sems design retrospective chart review setting tertiary referral medical center patients sixteen consecutive malignant hilar biliary obstruction patients interventions endoscopic palliative treatment malignant biliary obstruction zilver 635 sems december 2008 january 2010 main outcome measurements technical functional success rates early complications within 30 days stent placement early late stent occlusion biliary reintervention rates results total 49 zilver semss placed 16 patients mean age 61 years 6 men bismuth type ii n 4 iii n 5 iv n 7 lesions twelve cholangiocarcinoma 2 metastatic colon cancer 1 lung cancer 1 pancreatic cancer technical success rate 100 side side simultaneous bilateral stent deployment required achieved successfully 10 cases additional transpapillary stents placed potential future biliary access 30 day mortality rate 0 1 early 6 3 late 19 stent occlusions successful overall biliary drainage 75 limitations small sample size uncontrolled retrospective study conclusions malignant hilar biliary obstruction endoscopic palliation zilver 635 sems offers acceptable initial feasibility safety efficacy profiles current design facilitates smaller bile duct negotiation precise intrahepatic placement expanding available lengths allow transpapillary bridged bilateral sems placement future reobstructed biliary access long term studies required comparative outcomes current sems technology pubmed","probabilities":0.9799733,"Title":"Initial performance profile of a new 6F self-expanding metal stent for palliation of malignant hilar biliary obstruction","Abstract":"BACKGROUND: A 6F endoscopic biliary self-expanding metal stent (SEMS) has been newly introduced for intended simultaneous side-by-side bilateral deployment in hilar malignant obstruction. OBJECTIVE: To report our initial experience with the Zilver 635 biliary SEMS. DESIGN: Retrospective chart review. SETTING: Tertiary referral medical center. PATIENTS: Sixteen consecutive malignant hilar biliary obstruction patients. INTERVENTIONS: Endoscopic palliative treatment of malignant biliary obstruction with the Zilver 635 SEMS from December 2008 to January 2010. MAIN OUTCOME MEASUREMENTS: Technical/functional success rates, early complications (within 30 days of stent placement), early/late stent occlusion, and biliary reintervention rates. RESULTS: A total of 49 Zilver SEMSs were placed in 16 patients (mean age 61 years, 6 men) for Bismuth type II (n = 4), III (n = 5), and IV (n = 7) lesions. Twelve had cholangiocarcinoma, 2 had metastatic colon cancer, 1 had lung cancer, and 1 had pancreatic cancer. The technical success rate was 100%. Side-by-side simultaneous bilateral stent deployment was required and was achieved successfully in 10 cases. Additional transpapillary stents were placed for potential future biliary access. The 30-day mortality rate was 0%. There were 1 early (6%) and 3 late (19%) stent occlusions. Successful overall biliary drainage was 75%. LIMITATIONS: Small sample size, uncontrolled retrospective study. CONCLUSIONS: Malignant hilar biliary obstruction endoscopic palliation with the Zilver 635 SEMS offers acceptable initial feasibility, safety, and efficacy profiles. The current design facilitates smaller bile duct negotiation and more precise intrahepatic placement. Expanding available lengths would allow transpapillary bridged bilateral SEMS placement for future reobstructed biliary access. Further long-term studies are required for comparative outcomes with other current SEMS technology.","Source":"PubMed","category":"HUMAN","training_data":"Initial performance profile of a new 6F self-expanding metal stent for palliation of malignant hilar biliary obstruction BACKGROUND: A 6F endoscopic biliary self-expanding metal stent (SEMS) has been newly introduced for intended simultaneous side-by-side bilateral deployment in hilar malignant obstruction. OBJECTIVE: To report our initial experience with the Zilver 635 biliary SEMS. DESIGN: Retrospective chart review. SETTING: Tertiary referral medical center. PATIENTS: Sixteen consecutive malignant hilar biliary obstruction patients. INTERVENTIONS: Endoscopic palliative treatment of malignant biliary obstruction with the Zilver 635 SEMS from December 2008 to January 2010. MAIN OUTCOME MEASUREMENTS: Technical/functional success rates, early complications (within 30 days of stent placement), early/late stent occlusion, and biliary reintervention rates. RESULTS: A total of 49 Zilver SEMSs were placed in 16 patients (mean age 61 years, 6 men) for Bismuth type II (n = 4), III (n = 5), and IV (n = 7) lesions. Twelve had cholangiocarcinoma, 2 had metastatic colon cancer, 1 had lung cancer, and 1 had pancreatic cancer. The technical success rate was 100%. Side-by-side simultaneous bilateral stent deployment was required and was achieved successfully in 10 cases. Additional transpapillary stents were placed for potential future biliary access. The 30-day mortality rate was 0%. There were 1 early (6%) and 3 late (19%) stent occlusions. Successful overall biliary drainage was 75%. LIMITATIONS: Small sample size, uncontrolled retrospective study. CONCLUSIONS: Malignant hilar biliary obstruction endoscopic palliation with the Zilver 635 SEMS offers acceptable initial feasibility, safety, and efficacy profiles. The current design facilitates smaller bile duct negotiation and more precise intrahepatic placement. Expanding available lengths would allow transpapillary bridged bilateral SEMS placement for future reobstructed biliary access. Further long-term studies are required for comparative outcomes with other current SEMS technology. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma article focuses cholangiocarcinoma intrahepatic extrahepatic various classification schemes based anatomic location macroscopic growth pattern microscopic features cell origin outlined clinicopathologic immunohistochemical molecular differences intrahepatic cholangiocarcinoma extrahepatic cholangiocarcinoma well differences 2 subtypes intrahepatic cholangiocarcinoma discussed finally precursor lesions prognosis treatment promising new potential targeted therapies reviewed pubmed","probabilities":0.962963,"Title":"Cholangiocarcinoma","Abstract":"This article focuses on cholangiocarcinoma, both intrahepatic and extrahepatic. The various classification schemes based on anatomic location, macroscopic growth pattern, microscopic features, and cell of origin are outlined. The clinicopathologic, immunohistochemical and molecular differences between intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, as well as differences in the 2 subtypes of intrahepatic cholangiocarcinoma, are discussed. Finally, precursor lesions, prognosis, treatment, and promising new potential targeted therapies are reviewed.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma This article focuses on cholangiocarcinoma, both intrahepatic and extrahepatic. The various classification schemes based on anatomic location, macroscopic growth pattern, microscopic features, and cell of origin are outlined. The clinicopathologic, immunohistochemical and molecular differences between intrahepatic cholangiocarcinoma and extrahepatic cholangiocarcinoma, as well as differences in the 2 subtypes of intrahepatic cholangiocarcinoma, are discussed. Finally, precursor lesions, prognosis, treatment, and promising new potential targeted therapies are reviewed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognosis prognostic factors patients advanced biliary tract cancer depending anatomical location objective previous studies revealed biliary tract cancer btc different clinical characteristics depending anatomical location however clinical studies prognosis btc according anatomical location lacking aimed compare prognosis btc according anatomical location methods retrospectively reviewed records 311 patients advanced btc received gemcitabine based palliative chemotherapy january 2006 december 2015 samsung medical center results median follow 7 67 months median overall survival os times patients gallbladder gb cancer intrahepatic cholangiocellular carcinoma iccc extrahepatic cholangiocellular carcinoma eccc 8 1 months 7 7 months 13 4 months respectively median progression free survival pfs times gb cancer iccc eccc 4 1 months 5 4 months 7 2 months respectively multivariate analysis anatomical location cancer statistically significant factor os pfs p 001 prognostic factors associated os also different according anatomical location cancer ca 19 9 chemotherapy response gb cancer disease status albumin chemotherapy response iccc performance status chemotherapy response eccc conclusions prognosis prognostic factors btc significantly different depending anatomical location stn","probabilities":0.9799733,"Title":"Prognosis And Prognostic Factors In Patients With Advanced Biliary Tract Cancer Depending On Its Anatomical Location","Abstract":"Objective: Previous studies have revealed that biliary tract cancer (BTC) has different clinical characteristics depending on its anatomical location. However, clinical studies about the prognosis of BTC according to its anatomical location are lacking. We aimed to compare the prognosis of BTC according to its anatomical location. Methods: We retrospectively reviewed records of 311 patients with advanced BTC who received gemcitabine based palliative chemotherapy from January 2006 to December 2015 at Samsung medical Center. Results: During median follow-up of 7.67 months, the median overall survival (OS) times for patients with gallbladder (GB) cancer, intrahepatic cholangiocellular carcinoma (ICCC) and extrahepatic cholangiocellular carcinoma (ECCC) were 8.1 months, 7.7 months and 13.4 months, respectively. Median progression free survival (PFS) times for those with GB cancer, ICCC and ECCC were 4.1 months, 5.4 months and 7.2 months respectively. In multivariate analysis, anatomical location of cancer was a statistically significant factor for OS and PFS (p < .001). Prognostic factors associated with OS were also different according to the anatomical location of cancer: CA 19-9 and chemotherapy response for GB cancer; disease status, albumin and chemotherapy response for ICCC; performance status and chemotherapy response for ECCC. Conclusions: Prognosis and prognostic factors of BTC were significantly different depending on its anatomical location.","Source":"STN","category":"HUMAN","training_data":"Prognosis And Prognostic Factors In Patients With Advanced Biliary Tract Cancer Depending On Its Anatomical Location Objective: Previous studies have revealed that biliary tract cancer (BTC) has different clinical characteristics depending on its anatomical location. However, clinical studies about the prognosis of BTC according to its anatomical location are lacking. We aimed to compare the prognosis of BTC according to its anatomical location. Methods: We retrospectively reviewed records of 311 patients with advanced BTC who received gemcitabine based palliative chemotherapy from January 2006 to December 2015 at Samsung medical Center. Results: During median follow-up of 7.67 months, the median overall survival (OS) times for patients with gallbladder (GB) cancer, intrahepatic cholangiocellular carcinoma (ICCC) and extrahepatic cholangiocellular carcinoma (ECCC) were 8.1 months, 7.7 months and 13.4 months, respectively. Median progression free survival (PFS) times for those with GB cancer, ICCC and ECCC were 4.1 months, 5.4 months and 7.2 months respectively. In multivariate analysis, anatomical location of cancer was a statistically significant factor for OS and PFS (p < .001). Prognostic factors associated with OS were also different according to the anatomical location of cancer: CA 19-9 and chemotherapy response for GB cancer; disease status, albumin and chemotherapy response for ICCC; performance status and chemotherapy response for ECCC. Conclusions: Prognosis and prognostic factors of BTC were significantly different depending on its anatomical location. STN","prediction_labels":"HUMAN"},{"cleaned":"regional differences gallbladder cancer pathogenesis insights comparison cell cycle regulatory pi3k pro angiogenic protein expression background variable incidence gallbladder cancer gbca suggests regional pathogenetic differences study compares cell cycle regulatory angiogenesis related pi3k pathway protein expression gbcas three continents methods immunohistochemical expression several proteins assessed correlated clinicopathologic variables compared among centers chile fundaci n arturo l pez p rez falp japan yokohama city university ycu united states memorial sloan kettering cancer center mskcc hierarchical clustering used partition data based protein expression treatment center results tissue 117 patients mskcc 76 falp 22 ycu 19 analyzed mdm2 overexpression seen mskcc p 0 0001 absence p21 p 0 03 vegfr2 p 0 018 common p27 expression less frequent p 0 047 tumors ycu ki 67 labeling index ycu tumors median 10 two thirds lower centers hierarchical clustering analysis ycu patients p 0 017 early tumors p 0 017 clustered separately mskcc median disease specific survival curative intent r0 resection 27 months similar among centers p 0 9 median disease specific survival patients early tumors 28 4 months higher ycu reached p 0 06 conclusions cell cycle regulatory protein expression patterns ycu tumors differed treated falp mskcc differential clustering protein expression survival patients early tumors suggest regional differences pathogenesis disease biology stn","probabilities":1.0,"Title":"Regional Differences In Gallbladder Cancer Pathogenesis: Insights From A Comparison Of Cell Cycle-Regulatory Pi3K And Pro-Angiogenic Protein Expression","Abstract":"Background: The variable incidence of gallbladder cancer (GBCA) suggests regional pathogenetic differences. This study compares cell cycle-regulatory, angiogenesis-related, and PI3K pathway protein expression in GBCAs from three continents. \r\n\r\n Methods: Immunohistochemical expression of several proteins was assessed, correlated with clinicopathologic variables, and compared among centers from Chile (Fundación Arturo López Pérez [FALP]), Japan (Yokohama City University [YCU]), and the United States (Memorial Sloan-Kettering Cancer Center [MSKCC]). Hierarchical clustering was used to partition the data based on protein-expression and treatment center. \r\n\r\n Results: Tissue from 117 patients (MSKCC = 76; FALP = 22; YCU = 19) was analyzed. Mdm2 overexpression was seen only at MSKCC (p < 0.0001). Absence of p21 (p = 0.03) and VEGFR2 (p = 0.018) were more common and p27 expression was less frequent (p = 0.047) in tumors from YCU. Ki-67 labeling index in YCU tumors (median = 10) was two-thirds lower than at other centers. On hierarchical clustering analysis, all YCU patients (p = 0.017) and those with early tumors (p = 0.017) clustered separately from MSKCC. Median disease-specific survival after curative intent (R0) resection was 27 months and was similar among centers (p = 0.9). Median disease-specific survival of patients with early tumors was 28.4 months and was higher at YCU (not reached, p = 0.06). \r\n\r\n Conclusions: Cell cycle-regulatory protein expression patterns of YCU tumors differed from those treated at FALP and MSKCC. The differential clustering of protein expression and survival in patients with early tumors suggest regional differences in pathogenesis and disease biology.","Source":"STN","category":"ANIMAL","training_data":"Regional Differences In Gallbladder Cancer Pathogenesis: Insights From A Comparison Of Cell Cycle-Regulatory Pi3K And Pro-Angiogenic Protein Expression Background: The variable incidence of gallbladder cancer (GBCA) suggests regional pathogenetic differences. This study compares cell cycle-regulatory, angiogenesis-related, and PI3K pathway protein expression in GBCAs from three continents. \r\n\r\n Methods: Immunohistochemical expression of several proteins was assessed, correlated with clinicopathologic variables, and compared among centers from Chile (Fundación Arturo López Pérez [FALP]), Japan (Yokohama City University [YCU]), and the United States (Memorial Sloan-Kettering Cancer Center [MSKCC]). Hierarchical clustering was used to partition the data based on protein-expression and treatment center. \r\n\r\n Results: Tissue from 117 patients (MSKCC = 76; FALP = 22; YCU = 19) was analyzed. Mdm2 overexpression was seen only at MSKCC (p < 0.0001). Absence of p21 (p = 0.03) and VEGFR2 (p = 0.018) were more common and p27 expression was less frequent (p = 0.047) in tumors from YCU. Ki-67 labeling index in YCU tumors (median = 10) was two-thirds lower than at other centers. On hierarchical clustering analysis, all YCU patients (p = 0.017) and those with early tumors (p = 0.017) clustered separately from MSKCC. Median disease-specific survival after curative intent (R0) resection was 27 months and was similar among centers (p = 0.9). Median disease-specific survival of patients with early tumors was 28.4 months and was higher at YCU (not reached, p = 0.06). \r\n\r\n Conclusions: Cell cycle-regulatory protein expression patterns of YCU tumors differed from those treated at FALP and MSKCC. The differential clustering of protein expression and survival in patients with early tumors suggest regional differences in pathogenesis and disease biology. STN","prediction_labels":"ANIMAL"},{"cleaned":"trefoil factors tumor progression markers mitogens via egfr mapk activation cholangiocarcinoma aim investigate trefoil factor tff gene copy number mrna protein expression potential biomarkers cholangiocarcinoma cca methods tff mrna levels gene copy number protein expression determined respectively quantitative reverse transcription polymerase chain reaction pcr quantitative pcr immunohistochemistry bile duct epithelium biopsies collected individuals cca precancerous bile duct dysplasia disease free controls functional impact recombinant human rh tff2 peptide treatment proliferation epidermal growth factor receptor egfr mitogen activated protein kinase mapk signaling assessed cca cell line kmbc viable cell counting immunoblotting respectively results tff1 tff2 tff3 mrna expression significantly increased cca tissue compared disease free controls unrelated gene copy number tff1 immunoreactivity strongly increased dysplasia cca whereas tff2 immunoreactivity increased cca compared disease free controls contrast tff3 immunoreactivity moderately decreased dysplasia decreased cca kaplan meier analysis found association tff mrna protein copy number age gender histological subtype patient survival time treatment kmbc cells rhtff2 stimulated proliferation triggered phosphorylation egfr downstream extracellular signal related kinase erk whereas co incubation egfr tyrosine kinase inhibitor pd153035 blocked rhtff2 dependent proliferation egfr erk responses conclusion tff mrna protein expression indicative cca tumor progression predictive histological sub type survival time tff2 mitogenic cca via egfr mapk activation pubmed","probabilities":0.962963,"Title":"Trefoil factors: tumor progression markers and mitogens via EGFR/MAPK activation in cholangiocarcinoma","Abstract":"AIM: To investigate trefoil factor (TFF) gene copy number, mRNA and protein expression as potential biomarkers in cholangiocarcinoma (CCA). METHODS: TFF mRNA levels, gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction (PCR), quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA, precancerous bile duct dysplasia and from disease-free controls. The functional impact of recombinant human (rh)TFF2 peptide treatment on proliferation and epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling was assessed in the CCA cell line, KMBC, by viable cell counting and immunoblotting, respectively. RESULTS: TFF1, TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls, and was unrelated to gene copy number. TFF1 immunoreactivity was strongly increased in both dysplasia and CCA, whereas TFF2 immunoreactivity was increased only in CCA compared to disease-free controls. By contrast, TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA. Kaplan-Meier analysis found no association of TFF mRNA, protein and copy number with age, gender, histological subtype, and patient survival time. Treatment of KMBC cells with rhTFF2 stimulated proliferation, triggered phosphorylation of EGFR and downstream extracellular signal related kinase (ERK), whereas co-incubation with the EGFR tyrosine kinase inhibitor, PD153035, blocked rhTFF2-dependent proliferation and EGFR/ERK responses. CONCLUSION: TFF mRNA/protein expression is indicative of CCA tumor progression, but not predictive for histological sub-type or survival time. TFF2 is mitogenic in CCA via EGFR/MAPK activation.","Source":"PubMed","category":"HUMAN","training_data":"Trefoil factors: tumor progression markers and mitogens via EGFR/MAPK activation in cholangiocarcinoma AIM: To investigate trefoil factor (TFF) gene copy number, mRNA and protein expression as potential biomarkers in cholangiocarcinoma (CCA). METHODS: TFF mRNA levels, gene copy number and protein expression were determined respectively by quantitative reverse transcription polymerase chain reaction (PCR), quantitative PCR and immunohistochemistry in bile duct epithelium biopsies collected from individuals with CCA, precancerous bile duct dysplasia and from disease-free controls. The functional impact of recombinant human (rh)TFF2 peptide treatment on proliferation and epidermal growth factor receptor (EGFR)/mitogen-activated protein kinase (MAPK) signaling was assessed in the CCA cell line, KMBC, by viable cell counting and immunoblotting, respectively. RESULTS: TFF1, TFF2 and TFF3 mRNA expression was significantly increased in CCA tissue compared to disease-free controls, and was unrelated to gene copy number. TFF1 immunoreactivity was strongly increased in both dysplasia and CCA, whereas TFF2 immunoreactivity was increased only in CCA compared to disease-free controls. By contrast, TFF3 immunoreactivity was moderately decreased in dysplasia and further decreased in CCA. Kaplan-Meier analysis found no association of TFF mRNA, protein and copy number with age, gender, histological subtype, and patient survival time. Treatment of KMBC cells with rhTFF2 stimulated proliferation, triggered phosphorylation of EGFR and downstream extracellular signal related kinase (ERK), whereas co-incubation with the EGFR tyrosine kinase inhibitor, PD153035, blocked rhTFF2-dependent proliferation and EGFR/ERK responses. CONCLUSION: TFF mRNA/protein expression is indicative of CCA tumor progression, but not predictive for histological sub-type or survival time. TFF2 is mitogenic in CCA via EGFR/MAPK activation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ablative radiotherapy doses lead substantial prolongation survival patients inoperable intrahepatic cholangiocarcinoma retrospective dose response analysis purpose standard therapies localized inoperable intrahepatic cholangiocarcinoma ihcc ineffective advances radiotherapy rt techniques image guidance enabled ablative doses delivered large liver tumors study evaluated effects rt dose escalation treatment ihcc patients methods seventy nine consecutive patients inoperable ihcc identified treated definitive rt 2002 2014 diagnosis median tumor size 7 9 cm range 2 2 17 cm seventy patients 89 received systemic chemotherapy rt rt doses 35 100 gy median 58 05 gy three 30 fractions median biologic equivalent dose bed 80 5 gy range 43 75 180 gy results median follow time patients alive time analysis 33 months range 11 93 months median overall survival os time diagnosis 30 months 3 year os rate 44 radiation dose single important prognostic factor higher doses correlated improved local control lc rate os 3 year os rate patients receiving bed greater 80 5 gy 73 versus 38 receiving lower doses p 017 3 year lc rate significantly higher 78 bed greater 80 5 gy lower doses 45 p 04 bed continuous variable significantly affected lc p 009 os p 004 significant treatment related toxicities conclusion delivery higher doses rt improves lc os inoperable ihcc bed greater 80 5 gy seems ablative dose rt large ihccs long term survival rates compare favorably resection pubmed","probabilities":0.9799733,"Title":"Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis","Abstract":"PURPOSE: Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. PATIENTS AND METHODS: Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). RESULTS: Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. CONCLUSION: Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection.","Source":"PubMed","category":"HUMAN","training_data":"Ablative Radiotherapy Doses Lead to a Substantial Prolongation of Survival in Patients With Inoperable Intrahepatic Cholangiocarcinoma: A Retrospective Dose Response Analysis PURPOSE: Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. PATIENTS AND METHODS: Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). RESULTS: Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. CONCLUSION: Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"regional disparities surgical treatment gallbladder cancer abstract available google scholar","probabilities":0.9799733,"Title":"Regional Disparities In The Surgical Treatment Of Gallbladder Cancer","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Regional Disparities In The Surgical Treatment Of Gallbladder Cancer Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"regulation lncrna nef indicates poor prognosis intrahepatic cholangiocarcinoma lncrna nef tumor suppressor lncrna liver cancer present study aimed investigate role lncrna nef intrahepatic cholangiocarcinoma ihcc second common type primary cancer hepatobiliary system causes high mortality rate present study found lncrna nef regulated runt related transcription factor 1 runx1 regulated tumor tissues adjacent healthy tissues ihcc patients expression levels lncrna nef runx1 significantly reversely correlated tumor tissues adjacent healthy tissues plasma levels lncrna nef significantly lower ihcc patients healthy controls regulation lncrna nef effectively distinguished stage ii ihcc patients healthy controls patients followed 5 years patients high plasma levels lncrna nef showed significantly better survival conditions compared patients low expression levels lncrna nef lncrna nef overexpression led inhibited expression runx1 cells ihcc cell lines inhibited cancer cell migration invasion contrast runx1 overexpression showed significant effects lncrna nef expression attenuated effects lncrna nef overexpression cancer cell migration invasion therefore concluded lncrna nef participated ihcc possibly interacting runx1 stn","probabilities":0.9467213,"Title":"Down-Regulation Of Lncrna-Nef Indicates Poor Prognosis In Intrahepatic Cholangiocarcinoma","Abstract":"LncRNA-NEF is a tumor suppressor lncRNA in liver cancer. The present study aimed to investigate the role of lncRNA-NEF in intrahepatic cholangiocarcinoma (IHCC), which is second most common type of primary cancer of the hepatobiliary system that causes high mortality rate. In the present study we found that lncRNA-NEF was down-regulated, while Runt-related transcription factor 1 (RUNX1) was up-regulated in tumor tissues than in adjacent healthy tissues of IHCC patients. Expression levels of lncRNA-NEF and RUNX1 were significantly and reversely correlated in tumor tissues but not in adjacent healthy tissues. Plasma levels of lncRNA-NEF were significantly lower in IHCC patients than in healthy controls. Down-regulation of lncRNA-NEF effectively distinguished stage I and II IHCC patients from healthy controls. Patients were followed up for 5 years, patients with high plasma levels of lncRNA-NEF showed significantly better survival conditions compared with patients with low expression levels of lncRNA-NEF. LncRNA-NEF overexpression led to inhibited expression of RUNX1 in cells of IHCC cell lines and inhibited cancer cell migration and invasion. In contrast, RUNX1 overexpression showed no significant effects on lncRNA-NEF expression, but attenuated the effects of lncRNA-NEF overexpression on cancer cell migration and invasion. We therefore concluded that lncRNA-NEF participated in IHCC possibly by interacting with RUNX1.","Source":"STN","category":"ANIMAL","training_data":"Down-Regulation Of Lncrna-Nef Indicates Poor Prognosis In Intrahepatic Cholangiocarcinoma LncRNA-NEF is a tumor suppressor lncRNA in liver cancer. The present study aimed to investigate the role of lncRNA-NEF in intrahepatic cholangiocarcinoma (IHCC), which is second most common type of primary cancer of the hepatobiliary system that causes high mortality rate. In the present study we found that lncRNA-NEF was down-regulated, while Runt-related transcription factor 1 (RUNX1) was up-regulated in tumor tissues than in adjacent healthy tissues of IHCC patients. Expression levels of lncRNA-NEF and RUNX1 were significantly and reversely correlated in tumor tissues but not in adjacent healthy tissues. Plasma levels of lncRNA-NEF were significantly lower in IHCC patients than in healthy controls. Down-regulation of lncRNA-NEF effectively distinguished stage I and II IHCC patients from healthy controls. Patients were followed up for 5 years, patients with high plasma levels of lncRNA-NEF showed significantly better survival conditions compared with patients with low expression levels of lncRNA-NEF. LncRNA-NEF overexpression led to inhibited expression of RUNX1 in cells of IHCC cell lines and inhibited cancer cell migration and invasion. In contrast, RUNX1 overexpression showed no significant effects on lncRNA-NEF expression, but attenuated the effects of lncRNA-NEF overexpression on cancer cell migration and invasion. We therefore concluded that lncRNA-NEF participated in IHCC possibly by interacting with RUNX1. STN","prediction_labels":"ANIMAL"},{"cleaned":"neoadjuvant stereotactic body radiation therapy capecitabine liver transplantation unresectable hilar cholangiocarcinoma hilar cholangiocarcinoma cca difficult malignancy treat surgically anatomical location frequent association primary sclerosing cholangitis neoadjuvant chemoradiotherapy followed liver transplantation lymph node negative patients advanced select liver transplant centers treatment patients unresectable disease approach commonly used external beam radiotherapy combination biliary brachytherapy 5 fluorouracil based chemotherapy center recently embarked protocol using stereotactic body radiation therapy sbrt followed capecitabine lymph node negative patients liver transplantation therefore retrospectively determined tolerability pathological response pilot study 3 year period 17 patients unresectable hilar cca evaluated treatment protocol 12 patients qualified neoadjuvant therapy treated sbrt 50 60 gy 3 5 fractions course 2 weeks 1 week rest capecitabine initiated 1330 mg m 2 day continued liver transplantation neoadjuvant therapy 35 adverse events cholangitis palmar plantar erythrodysesthesia common capecitabine dose reductions required 5 occasions ultimately 9 patients listed transplantation 6 patients received liver transplant explant pathology hilar tumors showed least partial treatment response 5 patients extensive tumor necrosis fibrosis noted additionally high apoptotic indices low proliferative indices measured histological examinations eleven transplant related complications occurred 1 year survival rate transplantation 83 pilot study neoadjuvant therapy sbrt capecitabine liver transplantation unresectable cca demonstrated acceptable tolerability studies determine overall future efficacy therapy pubmed","probabilities":0.9799733,"Title":"Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma","Abstract":"Hilar cholangiocarcinoma (CCA) is a difficult malignancy to treat surgically because of its anatomical location and its frequent association with primary sclerosing cholangitis. Neoadjuvant chemoradiotherapy followed by liver transplantation in lymph node-negative patients has been advanced by select liver transplant centers for the treatment of patients with unresectable disease. This approach has most commonly used external-beam radiotherapy in combination with biliary brachytherapy and 5-fluorouracil-based chemotherapy. Our center recently embarked on a protocol using stereotactic body radiation therapy (SBRT) followed by capecitabine in lymph node-negative patients until liver transplantation. We, therefore, retrospectively determined the tolerability and pathological response in this pilot study. During a 3-year period, 17 patients with unresectable hilar CCA were evaluated for treatment under this protocol. In all, 12 patients qualified for neoadjuvant therapy and were treated with SBRT (50-60 Gy in 3-5 fractions over the course of 2 weeks). After 1 week of rest, capecitabine was initiated at 1330 mg/m(2) /day, and it was continued until liver transplantation. During neoadjuvant therapy, there were 35 adverse events in all, with cholangitis and palmar-plantar erythrodysesthesia being the most common. Capecitabine dose reductions were required on 5 occasions. Ultimately, 9 patients were listed for transplantation, and 6 patients received a liver transplant. The explant pathology of hilar tumors showed at least a partial treatment response in 5 patients, with extensive tumor necrosis and fibrosis noted. Additionally, high apoptotic indices and low proliferative indices were measured during histological examinations. Eleven transplant-related complications occurred, and the 1-year survival rate after transplantation was 83%. In this pilot study, neoadjuvant therapy with SBRT, capecitabine, and liver transplantation for unresectable CCA demonstrated acceptable tolerability. Further studies will determine the overall future efficacy of this therapy.","Source":"PubMed","category":"HUMAN","training_data":"Neoadjuvant stereotactic body radiation therapy, capecitabine, and liver transplantation for unresectable hilar cholangiocarcinoma Hilar cholangiocarcinoma (CCA) is a difficult malignancy to treat surgically because of its anatomical location and its frequent association with primary sclerosing cholangitis. Neoadjuvant chemoradiotherapy followed by liver transplantation in lymph node-negative patients has been advanced by select liver transplant centers for the treatment of patients with unresectable disease. This approach has most commonly used external-beam radiotherapy in combination with biliary brachytherapy and 5-fluorouracil-based chemotherapy. Our center recently embarked on a protocol using stereotactic body radiation therapy (SBRT) followed by capecitabine in lymph node-negative patients until liver transplantation. We, therefore, retrospectively determined the tolerability and pathological response in this pilot study. During a 3-year period, 17 patients with unresectable hilar CCA were evaluated for treatment under this protocol. In all, 12 patients qualified for neoadjuvant therapy and were treated with SBRT (50-60 Gy in 3-5 fractions over the course of 2 weeks). After 1 week of rest, capecitabine was initiated at 1330 mg/m(2) /day, and it was continued until liver transplantation. During neoadjuvant therapy, there were 35 adverse events in all, with cholangitis and palmar-plantar erythrodysesthesia being the most common. Capecitabine dose reductions were required on 5 occasions. Ultimately, 9 patients were listed for transplantation, and 6 patients received a liver transplant. The explant pathology of hilar tumors showed at least a partial treatment response in 5 patients, with extensive tumor necrosis and fibrosis noted. Additionally, high apoptotic indices and low proliferative indices were measured during histological examinations. Eleven transplant-related complications occurred, and the 1-year survival rate after transplantation was 83%. In this pilot study, neoadjuvant therapy with SBRT, capecitabine, and liver transplantation for unresectable CCA demonstrated acceptable tolerability. Further studies will determine the overall future efficacy of this therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical prognostic significance preoperative plasma hyperfibrinogenemia gallbladder cancer patients following surgical resection retrospective vitro study background coagulation fibrinolysis activation frequently observed cancer patients tumors cases thought associated higher risk invasion metastasis worse long term outcome objective study elucidate prognostic significance blood coagulation tests various clinicopathological characteristics patients gallbladder cancer gbc surgical resection methods retrospectively reviewed medical records 115 patients histologically confirmed gbc underwent surgical resection department prothrombin time pt activated partial thromboplastin time aptt thrombin time tt international normalized ratio inr fibrinogen levels platelet counts measured pretreatment time diagnosis predictive value fibrinogen levels tumor staging evaluated using receiver operating characteristic roc curve analysis correlations preoperative hyperfibrinogenemia clinicopathological characteristics analyzed univariate multivariate survival analyses performed identify factors associated overall survival os cancer cell migration invasion vitro examined investigate function fibrinogen gbc cell migration results plasma levels coagulation tests exception inr significantly different gbc patients control patients p 0 001 hyperfibrinogenemia 402 mg dl associated poorly differentiated tumors advanced tumor invasion lymphatic metastasis advanced tumor stage p 0 001 statistically significant adverse effect survival p 0 001 multivariate analysis hyperfibrinogenemia p 0 031 independently associated worse os tumor stage p 0 016 margin status p 0 001 lymphatic metastasis p 0 035 moreover cell migration invasion vitro significantly enhanced fibrinogen conclusions preoperative plasma fibrinogen levels associated tumor progression may independent marker poor prognosis gbc patients furthermore fibrinogen may contribute cell migration inducing epithelial mesenchymal transition pubmed","probabilities":1.0,"Title":"Clinical and prognostic significance of preoperative plasma hyperfibrinogenemia in gallbladder cancer patients following surgical resection: a retrospective and in vitro study","Abstract":"BACKGROUND: Coagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection. METHODS: We retrospectively reviewed the medical records of 115 patients with histologically confirmed GBC who underwent surgical resection in our department. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), international normalized ratio (INR), fibrinogen levels, and platelet counts were measured pretreatment at the time of diagnosis. The predictive value of fibrinogen levels for tumor staging was evaluated using a receiver operating characteristic (ROC) curve analysis. Correlations between the preoperative hyperfibrinogenemia and clinicopathological characteristics were analyzed, and univariate and multivariate survival analyses were performed to identify the factors associated with overall survival (OS). Cancer cell migration and invasion in vitro were examined to investigate the function of fibrinogen in GBC cell migration. RESULTS: The plasma levels for all coagulation tests, with the exception of INR, were significantly different between the GBC patients and control patients (p < 0.001). Hyperfibrinogenemia (>402 mg/dL) was associated with poorly differentiated tumors, advanced tumor invasion, lymphatic metastasis, and advanced tumor stage (p < 0.001), and had a statistically significant adverse effect on survival (p = 0.001). In the multivariate analysis, hyperfibrinogenemia (p = 0.031) was independently associated with worse OS, tumor stage (p = 0.016), margin status (p < 0.001), and lymphatic metastasis (p = 0.035). Moreover, cell migration and invasion in vitro were significantly enhanced by fibrinogen. CONCLUSIONS: Preoperative plasma fibrinogen levels was associated with tumor progression and may be an independent marker of poor prognosis in GBC patients. Furthermore, fibrinogen may contribute to cell migration by inducing epithelial-mesenchymal transition.","Source":"PubMed","category":"ANIMAL","training_data":"Clinical and prognostic significance of preoperative plasma hyperfibrinogenemia in gallbladder cancer patients following surgical resection: a retrospective and in vitro study BACKGROUND: Coagulation and fibrinolysis activation is frequently observed in cancer patients, and the tumors in these cases are thought to be associated with a higher risk of invasion, metastasis, and worse long-term outcome. The objective of this study was to elucidate the prognostic significance of blood coagulation tests and various clinicopathological characteristics in patients with gallbladder cancer (GBC) after surgical resection. METHODS: We retrospectively reviewed the medical records of 115 patients with histologically confirmed GBC who underwent surgical resection in our department. The prothrombin time (PT), activated partial thromboplastin time (aPTT), thrombin time (TT), international normalized ratio (INR), fibrinogen levels, and platelet counts were measured pretreatment at the time of diagnosis. The predictive value of fibrinogen levels for tumor staging was evaluated using a receiver operating characteristic (ROC) curve analysis. Correlations between the preoperative hyperfibrinogenemia and clinicopathological characteristics were analyzed, and univariate and multivariate survival analyses were performed to identify the factors associated with overall survival (OS). Cancer cell migration and invasion in vitro were examined to investigate the function of fibrinogen in GBC cell migration. RESULTS: The plasma levels for all coagulation tests, with the exception of INR, were significantly different between the GBC patients and control patients (p < 0.001). Hyperfibrinogenemia (>402 mg/dL) was associated with poorly differentiated tumors, advanced tumor invasion, lymphatic metastasis, and advanced tumor stage (p < 0.001), and had a statistically significant adverse effect on survival (p = 0.001). In the multivariate analysis, hyperfibrinogenemia (p = 0.031) was independently associated with worse OS, tumor stage (p = 0.016), margin status (p < 0.001), and lymphatic metastasis (p = 0.035). Moreover, cell migration and invasion in vitro were significantly enhanced by fibrinogen. CONCLUSIONS: Preoperative plasma fibrinogen levels was associated with tumor progression and may be an independent marker of poor prognosis in GBC patients. Furthermore, fibrinogen may contribute to cell migration by inducing epithelial-mesenchymal transition. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"targeting aspartate beta hydroxylase small molecule inhibitor mo 1182 suppresses cholangiocarcinoma metastasis background cholangiocarcinoma devastating disease 2 5 year survival disease spread outside liver enzyme aspartate beta hydroxylase asph demonstrated highly expressed cholangiocarcinoma normal bile ducts found stimulate tumor cell migration addition found targeting asph inhibits cholangiocarcinoma malignant progression however clear whether targeting asph small molecule inhibitor mo 1182 suppresses cholangiocarcinoma metastasis current study aims study efficacy mo 1182 suppressing cholangiocarcinoma metastasis methods analysis performed vitro vivo preclinical animal model using molecular biochemical strategies regulate asph expression function results knockdown asph substantially inhibited cell migration invasion two human cholangiocarcinoma cell lines targeting asph small molecule inhibitor suppressed cholangiocarcinoma progression molecular mechanism studies demonstrated knockdown asph subsequently suppressed protein levels matrix metalloproteinases asph knockdown experiments suggest enzyme may modulate cholangiocarcinoma metastasis regulating matrix metalloproteinases expression furthermore using asph inhibitor rat cholangiocarcinoma intrahepatic model established bed neu cl 24 cholangiocarcinoma cells found targeting asph inhibited intrahepatic cholangiocarcinoma metastasis downstream expression matrix metalloproteinases conclusion asph may modulate cholangiocarcinoma metastasis via matrix metalloproteinases expression taken together targeting asph function may inhibit intrahepatic cholangiocarcinoma metastasis improve survival stn","probabilities":0.9467213,"Title":"Targeting Aspartate Beta-Hydroxylase With The Small Molecule Inhibitor Mo-I-1182 Suppresses Cholangiocarcinoma Metastasis","Abstract":"Background: Cholangiocarcinoma is a devastating disease with a 2% 5-year survival if the disease has spread outside the liver. The enzyme aspartate beta-hydroxylase (ASPH) has been demonstrated to be highly expressed in cholangiocarcinoma but not in normal bile ducts and found to stimulate tumor cell migration. In addition, it was found that targeting ASPH inhibits cholangiocarcinoma malignant progression. However, it is not clear whether targeting ASPH with the small molecule inhibitor MO-I-1182 suppresses cholangiocarcinoma metastasis. The current study aims to study the efficacy of MO-I-1182 in suppressing cholangiocarcinoma metastasis. \r\n\r\n Methods: The analysis was performed in vitro and in vivo with a preclinical animal model by using molecular and biochemical strategies to regulate ASPH expression and function. \r\n\r\n Results: Knockdown of ASPH substantially inhibited cell migration and invasion in two human cholangiocarcinoma cell lines. Targeting ASPH with a small molecule inhibitor suppressed cholangiocarcinoma progression. Molecular mechanism studies demonstrated that knockdown of ASPH subsequently suppressed protein levels of the matrix metalloproteinases. The ASPH knockdown experiments suggest that this enzyme may modulate cholangiocarcinoma metastasis by regulating matrix metalloproteinases expression. Furthermore, using an ASPH inhibitor in a rat cholangiocarcinoma intrahepatic model established with BED-Neu-CL#24 cholangiocarcinoma cells, it was found that targeting ASPH inhibited intrahepatic cholangiocarcinoma metastasis and downstream expression of the matrix metalloproteinases. \r\n\r\n Conclusion: ASPH may modulate cholangiocarcinoma metastasis via matrix metalloproteinases expression. Taken together, targeting ASPH function may inhibit intrahepatic cholangiocarcinoma metastasis and improve survival.","Source":"STN","category":"ANIMAL","training_data":"Targeting Aspartate Beta-Hydroxylase With The Small Molecule Inhibitor Mo-I-1182 Suppresses Cholangiocarcinoma Metastasis Background: Cholangiocarcinoma is a devastating disease with a 2% 5-year survival if the disease has spread outside the liver. The enzyme aspartate beta-hydroxylase (ASPH) has been demonstrated to be highly expressed in cholangiocarcinoma but not in normal bile ducts and found to stimulate tumor cell migration. In addition, it was found that targeting ASPH inhibits cholangiocarcinoma malignant progression. However, it is not clear whether targeting ASPH with the small molecule inhibitor MO-I-1182 suppresses cholangiocarcinoma metastasis. The current study aims to study the efficacy of MO-I-1182 in suppressing cholangiocarcinoma metastasis. \r\n\r\n Methods: The analysis was performed in vitro and in vivo with a preclinical animal model by using molecular and biochemical strategies to regulate ASPH expression and function. \r\n\r\n Results: Knockdown of ASPH substantially inhibited cell migration and invasion in two human cholangiocarcinoma cell lines. Targeting ASPH with a small molecule inhibitor suppressed cholangiocarcinoma progression. Molecular mechanism studies demonstrated that knockdown of ASPH subsequently suppressed protein levels of the matrix metalloproteinases. The ASPH knockdown experiments suggest that this enzyme may modulate cholangiocarcinoma metastasis by regulating matrix metalloproteinases expression. Furthermore, using an ASPH inhibitor in a rat cholangiocarcinoma intrahepatic model established with BED-Neu-CL#24 cholangiocarcinoma cells, it was found that targeting ASPH inhibited intrahepatic cholangiocarcinoma metastasis and downstream expression of the matrix metalloproteinases. \r\n\r\n Conclusion: ASPH may modulate cholangiocarcinoma metastasis via matrix metalloproteinases expression. Taken together, targeting ASPH function may inhibit intrahepatic cholangiocarcinoma metastasis and improve survival. STN","prediction_labels":"ANIMAL"},{"cleaned":"determining role external beam radiotherapy unresectable intrahepatic cholangiocarcinoma retrospective analysis 84 patients background intrahepatic cholangiocarcinoma icc second common type primary liver cancer studies focused palliative radiotherapy used patients weren suitable resection surgery study conducted investigate effect external beam radiotherapy ebrt patients unresectable icc methods identified 84 patients icc december 1998 december 2008 retrospective analysis thirty five 84 patients received ebrt therapy five times week median dose 50 gy dose range 30 60 gy fractions 1 8 2 0 gy daily ebrt group remaining 49 patients comprised non ebrt group tumor response jaundice relief survival rates compared kaplan meier analysis patient records reviewed compared using cox proportional hazard analysis determine factors affect survival time icc results ebrt complete response cr partial response pr primary tumors observed 8 6 28 5 patients respectively cr pr lymph node metastases observed 20 40 patients 19 patients jaundice complete partial relief observed 36 8 31 6 patients respectively median survival times 5 1 months non ebrt group 9 5 months ebrt group p 0 003 one two year survival rates ebrt versus non ebrt group 38 5 versus 16 4 9 6 versus 4 9 respectively multivariate analysis revealed clinical symptoms larger tumor size ebrt multiple nodules synchronous lymph node metastases associated poorer prognosis conclusions ebrt palliative care appears improve prognosis relieve symptom jaundice patients unresectable icc pubmed","probabilities":0.9799733,"Title":"Determining the role of external beam radiotherapy in unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 84 patients","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary liver cancer. Only few studies have focused on palliative radiotherapy used for patients who weren't suitable for resection by surgery. This study was conducted to investigate the effect of external beam radiotherapy (EBRT) for patients with unresectable ICC. METHODS: We identified 84 patients with ICC from December 1998 through December 2008 for retrospective analysis. Thirty-five of 84 patients received EBRT therapy five times a week (median dose, 50 Gy; dose range, 30-60 Gy, in fractions of 1.8-2.0 Gy daily; EBRT group); the remaining 49 patients comprised the non-EBRT group. Tumor response, jaundice relief, and survival rates were compared by Kaplan-Meier analysis. Patient records were reviewed and compared using Cox proportional hazard analysis to determine factors that affect survival time in ICC. RESULTS: After EBRT, complete response (CR) and partial response (PR) of primary tumors were observed in 8.6% and 28.5% of patients, respectively, and CR and PR of lymph node metastases were observed in 20% and 40% of patients. In 19 patients with jaundice, complete and partial relief was observed in 36.8% and 31.6% of patients, respectively. Median survival times were 5.1 months for the non-EBRT group and 9.5 months for the EBRT group (P = 0.003). One-and two-year survival rates for EBRT versus non-EBRT group were 38.5% versus 16.4%, and 9.6% versus 4.9%, respectively. Multivariate analysis revealed that clinical symptoms, larger tumor size, no EBRT, multiple nodules and synchronous lymph node metastases were associated with poorer prognosis. CONCLUSIONS: EBRT as palliative care appears to improve prognosis and relieve the symptom of jaundice in patients with unresectable ICC.","Source":"PubMed","category":"HUMAN","training_data":"Determining the role of external beam radiotherapy in unresectable intrahepatic cholangiocarcinoma: a retrospective analysis of 84 patients BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common type of primary liver cancer. Only few studies have focused on palliative radiotherapy used for patients who weren't suitable for resection by surgery. This study was conducted to investigate the effect of external beam radiotherapy (EBRT) for patients with unresectable ICC. METHODS: We identified 84 patients with ICC from December 1998 through December 2008 for retrospective analysis. Thirty-five of 84 patients received EBRT therapy five times a week (median dose, 50 Gy; dose range, 30-60 Gy, in fractions of 1.8-2.0 Gy daily; EBRT group); the remaining 49 patients comprised the non-EBRT group. Tumor response, jaundice relief, and survival rates were compared by Kaplan-Meier analysis. Patient records were reviewed and compared using Cox proportional hazard analysis to determine factors that affect survival time in ICC. RESULTS: After EBRT, complete response (CR) and partial response (PR) of primary tumors were observed in 8.6% and 28.5% of patients, respectively, and CR and PR of lymph node metastases were observed in 20% and 40% of patients. In 19 patients with jaundice, complete and partial relief was observed in 36.8% and 31.6% of patients, respectively. Median survival times were 5.1 months for the non-EBRT group and 9.5 months for the EBRT group (P = 0.003). One-and two-year survival rates for EBRT versus non-EBRT group were 38.5% versus 16.4%, and 9.6% versus 4.9%, respectively. Multivariate analysis revealed that clinical symptoms, larger tumor size, no EBRT, multiple nodules and synchronous lymph node metastases were associated with poorer prognosis. CONCLUSIONS: EBRT as palliative care appears to improve prognosis and relieve the symptom of jaundice in patients with unresectable ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effects preoperative neutrophil lymphocyte platelet lymphocyte ratios survival patients extrahepatic cholangiocarcinoma background aim indicators systemic inflammatory response neutrophil lymphocyte ratio nlr platelet lymphocyte ratio plr predict prognoses various cancers study investigated prognostic significance extrahepatic cholangiocarcinoma ecc patients methods analyzed 120 patients underwent surgery ecc 2000 2014 calculated preoperative nlr plr evaluated correlations patients clinicopathological features prognosis results although high nlr associated worse recurrence free survival rfs hazard ratio hr 1 32 p 0 26 cancer specific survival css hr 1 35 p 0 31 overall survival os hr 1 19 p 0 52 high plr significantly associated worse rfs hr 1 85 p 0 01 css hr 2 38 p 0 002 os hr 1 98 p 0 008 multivariate analysis high plr hr 1 89 p 0 02 lymph node metastasis hr 1 78 p 0 03 independent prognostic factors os high plr liver recurrences p 0 04 recurrences within 1 year hr 2 38 p 0 02 low plr conclusion high preoperative plr independent predictor poor prognosis patients ecc underwent resections pubmed","probabilities":0.9799733,"Title":"Effects of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios on Survival in Patients with Extrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND/AIM: As indicators of systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict prognoses for various cancers. This study investigated their prognostic significance in extrahepatic cholangiocarcinoma (ECC). PATIENTS AND METHODS: We analyzed 120 patients who underwent surgery for ECC between 2000 and 2014. We calculated preoperative NLR and PLR and evaluated their correlations with patients' clinicopathological features and prognosis. RESULTS: Although high NLR was not associated with worse recurrence-free survival (RFS) (hazard ratio (HR)=1.32, p=0.26), cancer-specific survival (CSS) (HR=1.35, p=0.31) and overall survival (OS) (HR=1.19, p=0.52), high PLR was significantly associated with worse RFS (HR=1.85, p=0.01), CSS (HR=2.38, p=0.002) and OS (HR=1.98, p=0.008). In multivariate analysis, high PLR (HR=1.89, p=0.02) and lymph node metastasis (HR=1.78, p=0.03) were independent prognostic factors for OS. A high PLR had more liver recurrences (p=0.04) and recurrences within 1 year (HR=2.38, p=0.02) than low PLR. CONCLUSION: High preoperative PLR was an independent predictor of poor prognosis for patients with ECC who underwent resections.","Source":"PubMed","category":"HUMAN","training_data":"Effects of Preoperative Neutrophil-to-Lymphocyte and Platelet-to-Lymphocyte Ratios on Survival in Patients with Extrahepatic Cholangiocarcinoma BACKGROUND/AIM: As indicators of systemic inflammatory response, the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) predict prognoses for various cancers. This study investigated their prognostic significance in extrahepatic cholangiocarcinoma (ECC). PATIENTS AND METHODS: We analyzed 120 patients who underwent surgery for ECC between 2000 and 2014. We calculated preoperative NLR and PLR and evaluated their correlations with patients' clinicopathological features and prognosis. RESULTS: Although high NLR was not associated with worse recurrence-free survival (RFS) (hazard ratio (HR)=1.32, p=0.26), cancer-specific survival (CSS) (HR=1.35, p=0.31) and overall survival (OS) (HR=1.19, p=0.52), high PLR was significantly associated with worse RFS (HR=1.85, p=0.01), CSS (HR=2.38, p=0.002) and OS (HR=1.98, p=0.008). In multivariate analysis, high PLR (HR=1.89, p=0.02) and lymph node metastasis (HR=1.78, p=0.03) were independent prognostic factors for OS. A high PLR had more liver recurrences (p=0.04) and recurrences within 1 year (HR=2.38, p=0.02) than low PLR. CONCLUSION: High preoperative PLR was an independent predictor of poor prognosis for patients with ECC who underwent resections. PubMed","prediction_labels":"HUMAN"},{"cleaned":"stereotactic body radiotherapy dose impact local control overall survival patients locally advanced intrahepatic extrahepatic cholangiocarcinoma purpose non resectable cholangiocarcinoma ccc significant therapeutic challenge bad prognosis study analyzed outcome sbrt intra extrahepatic ccc material methods sixty four patients 82 ccc lesions retrospective multicenter database analyzed available parameters analyzed local control lc overall survival os toxicity results median follow time patients alive 35 months range 7 91 months median overall survival os time 15 months 2 year 3 year os rates 32 21 median prescribed biological effective radiation dose bed 10 67 2 gy 10 range 36 115 gy 10 sd 20 gy 10 median 8 fractions range 3 17 95 ci 3 12 median bed max 91 gy 10 bed prognostic factor lc os patients receiving bed max 91 gy 10 median os 24 months vs 13 months receiving lower doses p 0 008 lc rates 12 24 months 91 80 bed max 91 gy 10 vs 66 39 lower doses p 0 009 note tumor size ptv neither predictive prognostic lc os treatment tolerance good 17 grade 1 gastroduodenitis 11 grade 2 3 cholangitis 4 7 grade 3 gastrointestinal bleeding conclusion largest reported series sbrt cholangiocarcinoma overall survival local control significantly improved higher doses bed tolerance excellent pubmed","probabilities":0.9799733,"Title":"Stereotactic body radiotherapy dose and its impact on local control and overall survival of patients for locally advanced intrahepatic and extrahepatic cholangiocarcinoma","Abstract":"PURPOSE: Non-resectable cholangiocarcinoma (CCC) is a significant therapeutic challenge because of bad prognosis. This study analyzed the outcome after SBRT for intra- and extrahepatic CCC. MATERIAL AND METHODS: Sixty-four patients with 82 CCC lesions from a retrospective multicenter database were analyzed. Available parameters were analyzed for local control (LC), overall survival (OS) and toxicity. RESULTS: Median follow-up time for patients alive was 35 months (range 7-91 months). Median overall survival (OS) time was 15 months; 2-year and 3-year OS rates were 32% and 21%. Median prescribed biological effective radiation dose (BED, α/β = 10) was 67.2 Gy(10) (range, 36-115 Gy(10); SD: 20 Gy(10)) in median 8 fractions (range, 3-17; 95% CI: 3-12), median BED(max) was 91 Gy(10). BED was the only prognostic factor for LC and OS. Patients receiving BED(max) >91 Gy(10) had a median OS of 24 months vs. 13 months for those receiving lower doses (p = 0.008). LC rates at 12 and 24 months were 91% and 80% for BED(max) >91 Gy(10) vs. 66% and 39% for lower doses (p = 0.009). Of note, tumor size and PTV were neither predictive nor prognostic for LC and OS. Treatment tolerance was good with 17% of grade 1 gastroduodenitis, 11% of grade 2-3 cholangitis and 4.7% of grade 3 gastrointestinal bleeding. CONCLUSION: This is the largest reported series on SBRT in cholangiocarcinoma. Overall survival and local control were significantly improved after higher doses (BED) and tolerance was excellent.","Source":"PubMed","category":"HUMAN","training_data":"Stereotactic body radiotherapy dose and its impact on local control and overall survival of patients for locally advanced intrahepatic and extrahepatic cholangiocarcinoma PURPOSE: Non-resectable cholangiocarcinoma (CCC) is a significant therapeutic challenge because of bad prognosis. This study analyzed the outcome after SBRT for intra- and extrahepatic CCC. MATERIAL AND METHODS: Sixty-four patients with 82 CCC lesions from a retrospective multicenter database were analyzed. Available parameters were analyzed for local control (LC), overall survival (OS) and toxicity. RESULTS: Median follow-up time for patients alive was 35 months (range 7-91 months). Median overall survival (OS) time was 15 months; 2-year and 3-year OS rates were 32% and 21%. Median prescribed biological effective radiation dose (BED, α/β = 10) was 67.2 Gy(10) (range, 36-115 Gy(10); SD: 20 Gy(10)) in median 8 fractions (range, 3-17; 95% CI: 3-12), median BED(max) was 91 Gy(10). BED was the only prognostic factor for LC and OS. Patients receiving BED(max) >91 Gy(10) had a median OS of 24 months vs. 13 months for those receiving lower doses (p = 0.008). LC rates at 12 and 24 months were 91% and 80% for BED(max) >91 Gy(10) vs. 66% and 39% for lower doses (p = 0.009). Of note, tumor size and PTV were neither predictive nor prognostic for LC and OS. Treatment tolerance was good with 17% of grade 1 gastroduodenitis, 11% of grade 2-3 cholangitis and 4.7% of grade 3 gastrointestinal bleeding. CONCLUSION: This is the largest reported series on SBRT in cholangiocarcinoma. Overall survival and local control were significantly improved after higher doses (BED) and tolerance was excellent. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment unresectable intrahepatic cholangiocarcinoma yttrium 90 radioembolization systematic review pooled analysis radioembolization yttrium 90 microspheres offers alternative treatment option patients unresectable intrahepatic cholangiocarcinoma icc however rarity heterogeneity icc makes difficult draw firm conclusions treatment efficacy therefore goal current study systematically review existing literature surrounding treatment unresectable iccs yttrium 90 microspheres provide comprehensive review current experience clinical outcome treatment modality performed comprehensive search electronic databases icc treatment identified 12 studies relevant data regarding radioembolization therapy yttrium 90 microspheres based pooled analysis overall weighted median survival 15 5 months tumour response based radiological studies demonstrated partial response 28 stable disease 54 patients three months seven patients able downstaged surgical resection complication profile radioembolization similar intra arterial treatment modalities overall survival patients icc treatment yttrium 90 microspheres higher historical survival rates shows similar survival patients treated systemic chemotherapy trans arterial chemoembolization therapy therefore use yttrium 90 microspheres considered list available treatment options icc however future randomized trials comparing systemic chemotherapy tace local radiation required identify optimal treatment modality unresectable icc pubmed","probabilities":0.9799733,"Title":"Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis","Abstract":"Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC.","Source":"PubMed","category":"HUMAN","training_data":"Treatment of unresectable intrahepatic cholangiocarcinoma with yttrium-90 radioembolization: a systematic review and pooled analysis Radioembolization with yttrium-90 microspheres offers an alternative treatment option for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, the rarity and heterogeneity of ICC makes it difficult to draw firm conclusions about treatment efficacy. Therefore, the goal of the current study is to systematically review the existing literature surrounding treatment of unresectable ICCs with yttrium-90 microspheres and provide a comprehensive review of the current experience and clinical outcome of this treatment modality. We performed a comprehensive search of electronic databases for ICC treatment and identified 12 studies with relevant data regarding radioembolization therapy with yttrium-90 microspheres. Based on pooled analysis, the overall weighted median survival was 15.5 months. Tumour response based on radiological studies demonstrated a partial response in 28% and stable disease in 54% of patients at three months. Seven patients were able to be downstaged to surgical resection. The complication profile of radioembolization is similar to that of other intra-arterial treatment modalities. Overall survival of patients with ICC after treatment with yttrium-90 microspheres is higher than historical survival rates and shows similar survival to those patients treated with systemic chemotherapy and/or trans-arterial chemoembolization therapy. Therefore, the use of yttrium-90 microspheres should be considered in the list of available treatment options for ICC. However, future randomized trials comparing systemic chemotherapy, TACE and local radiation will be required to identify the optimal treatment modality for unresectable ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"liver transplant post neoadjuvant chemo radiotherapy hilar cholangiocarcinoma technical challenge higher risk transplant background neoadjuvant chemo radiotherapy followed liver transplantation option long term survival selected patients unresectable hilar cholangiocarcinoma hcca potentially higher morbidity due radiotherapy effects hepatic hilum one main concerns preventing diffusion treatment protocol methods patients underwent liver transplant requiring aortic conduit hepatico jejunostomy october 2004 december 2016 included study rate vascular biliary complications compared patients underwent chemo radiotherapy liver transplantation hcca patients liver transplant alone indication control group results hcca group included 26 patients control group 36 patients 2 groups comparable demographic characteristics comorbidities waiting list time morbidity 53 hcca group vs 61 control group p 0 610 90 day mortality 15 vs 14 p 1 similar groups well relaparotomy 12 vs 33 p 0 208 retransplantation rates 15 vs 17 p 1 incidence vascular complication 27 hcca group 19 control group p 0 547 common vascular complication hepatic artery thrombosis groups 23 vs 17 p 0 536 followed stenosis cava anastomosis 12 vs 6 p 0 641 portal vein thrombosis stenosis 8 vs 0 p 0 172 rate bile leak 15 vs 11 p 0 710 biliary stricture 8 vs 2 p 0 263 also comparable 5 year graft survival 48 7 hcca group 68 1 control group p 0 288 conclusion experience use neoadjuvant chemo radiotherapy didn translate higher incidence vascular biliary complications therefore liver transplant hcca performed safely despite potential technical challenges google scholar","probabilities":0.9799733,"Title":"Liver Transplant Post Neoadjuvant Chemo-Radiotherapy For Hilar Cholangiocarcinoma: A Technical Challenge But Not A Higher Risk Transplant","Abstract":"Background: Neoadjuvant chemo-radiotherapy followed by liver\ntransplantation is the only option for long term survival in selected patients with unresectable hilar cholangiocarcinoma (hCCA). The\npotentially higher morbidity, due to the radiotherapy effects on the\nhepatic hilum, is one of the main concerns preventing the diffusion\nof this treatment protocol.\nMethods: All the patients who underwent a liver transplant requiring an aortic conduit and a hepatico-jejunostomy between October\n2004 and December 2016 were included in the study. The rate of vascular and biliary complications was compared between patients who\nunderwent chemo-radiotherapy and liver transplantation for hCCA\nand patients who had liver transplant alone for any other indication\n(control group).\nResults: The hCCA group included 26 patients, the control group 36\npatients. The 2 groups were comparable for demographic characteristics, comorbidities and waiting list time. Morbidity (53% in the\nhCCA group vs 61% in the control group, p=0.610) and 90-day mortality\n(15% vs 14%, p=1) were similar between the groups, as well as the\nrelaparotomy (12% vs 33%, p=0.208) and retransplantation rates (15%\nvs 17%, p=1). The incidence of vascular complication was 27% in the\nhCCA group and 19% in the control group (p=0.547). The most common\nvascular complication was hepatic artery thrombosis in both groups\n(23% vs 17%, p=0.536), followed by stenosis of the cava anastomosis\n(12% vs 6%, p=0.641) and portal vein thrombosis/stenosis (8% vs 0% p=0.172). The rate of bile leak (15% vs 11%, p=0.710) and biliary stricture\n(8% vs 2%, p=0.263) were also comparable. The 5-year graft survival\nwas 48.7% in the hCCA group and 68.1% in the control group (p=0.288).\nConclusion: In our experience the use of neoadjuvant chemo-radiotherapy didn‘t translate into a higher incidence of vascular or biliary\ncomplications; therefore, liver transplant for hCCA can be performed\nsafely despite the potential technical challenges.","Source":"Google Scholar","category":"HUMAN","training_data":"Liver Transplant Post Neoadjuvant Chemo-Radiotherapy For Hilar Cholangiocarcinoma: A Technical Challenge But Not A Higher Risk Transplant Background: Neoadjuvant chemo-radiotherapy followed by liver\ntransplantation is the only option for long term survival in selected patients with unresectable hilar cholangiocarcinoma (hCCA). The\npotentially higher morbidity, due to the radiotherapy effects on the\nhepatic hilum, is one of the main concerns preventing the diffusion\nof this treatment protocol.\nMethods: All the patients who underwent a liver transplant requiring an aortic conduit and a hepatico-jejunostomy between October\n2004 and December 2016 were included in the study. The rate of vascular and biliary complications was compared between patients who\nunderwent chemo-radiotherapy and liver transplantation for hCCA\nand patients who had liver transplant alone for any other indication\n(control group).\nResults: The hCCA group included 26 patients, the control group 36\npatients. The 2 groups were comparable for demographic characteristics, comorbidities and waiting list time. Morbidity (53% in the\nhCCA group vs 61% in the control group, p=0.610) and 90-day mortality\n(15% vs 14%, p=1) were similar between the groups, as well as the\nrelaparotomy (12% vs 33%, p=0.208) and retransplantation rates (15%\nvs 17%, p=1). The incidence of vascular complication was 27% in the\nhCCA group and 19% in the control group (p=0.547). The most common\nvascular complication was hepatic artery thrombosis in both groups\n(23% vs 17%, p=0.536), followed by stenosis of the cava anastomosis\n(12% vs 6%, p=0.641) and portal vein thrombosis/stenosis (8% vs 0% p=0.172). The rate of bile leak (15% vs 11%, p=0.710) and biliary stricture\n(8% vs 2%, p=0.263) were also comparable. The 5-year graft survival\nwas 48.7% in the hCCA group and 68.1% in the control group (p=0.288).\nConclusion: In our experience the use of neoadjuvant chemo-radiotherapy didn‘t translate into a higher incidence of vascular or biliary\ncomplications; therefore, liver transplant for hCCA can be performed\nsafely despite the potential technical challenges. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"hmgb1 correlates angiogenesis poor prognosis perihilar cholangiocarcinoma via elevating vegfr2 vessel endothelium perihilar cholangiocarcinoma phcca common type cholangiocarcinoma low resection rate high morbidity study phcca biomarkers made progresses slowly compared intrahepatic cholangiocarcinoma surgical complexity low possibility radical surgery resulted difficulty specimen obtainment screen identify new biomarkers phcca constructed retrospective cohort 121 phcca patients prospective cohort consisting 64 phcca patients screened candidate biomarkers immunohistochemistry quantified pcr study expression high mobility group box 1 hmgb1 demonstrated significantly associated microvascular density mvd unfavorable prognosis phcca retrospective prospective study moreover hmgb1 concentrations bile serum phcca patients healthy controls detected compared postoperative serum hmgb1 reflux cholangitis indicated recurrence unfavorable prognosis phcca experiments vitro vivo demonstrated intracellular hmgb1 released phcca cells induce invasion angiogenesis lps stimulation vegfr2 expression vessel endothelial cells upregulated released hmgb1 phcca resulting ectopic angiogenesis conclusion intracellular hmgb1 released phcca cells promote angiogenesis via elevating vegfr2 vessel endothelial cells high expression hmgb1 associated mvd poor prognosis clinical analyzation postoperative serum hmgb1 cholangitis predict high recurrence unfavorable prognosis pubmed","probabilities":0.9799733,"Title":"HMGB1 correlates with angiogenesis and poor prognosis of perihilar cholangiocarcinoma via elevating VEGFR2 of vessel endothelium","Abstract":"Perihilar cholangiocarcinoma (PHCCA) is the most common type of cholangiocarcinoma with low resection rate and high morbidity. The study of PHCCA biomarkers made progresses slowly compared with intrahepatic cholangiocarcinoma because of surgical complexity and low possibility of radical surgery, which resulted in the difficulty of specimen obtainment. To screen and identify new biomarkers in PHCCA, we constructed a retrospective cohort with 121 PHCCA patients and a prospective cohort consisting of 64 PHCCA patients, and screened the candidate biomarkers by immunohistochemistry and quantified PCR. In our study, expression of high mobility group box 1 (HMGB1) was demonstrated to be significantly associated with microvascular density (MVD) and unfavorable prognosis of PHCCA in both retrospective and prospective study. Moreover, HMGB1 concentrations in bile and serum of PHCCA patients and healthy controls were detected and compared. Postoperative serum HMGB1 and reflux cholangitis indicated recurrence and unfavorable prognosis of PHCCA. With experiments in vitro and in vivo, we demonstrated that intracellular HMGB1 could be released from PHCCA cells and induce invasion and angiogenesis with LPS stimulation. VEGFR2 expression in vessel endothelial cells was upregulated by the released HMGB1 from PHCCA, resulting in the ectopic angiogenesis. In conclusion, intracellular HMGB1 could be released from PHCCA cells and promote angiogenesis via elevating VEGFR2 in vessel endothelial cells. High expression of HMGB1 was associated with MVD and poor prognosis in clinical analyzation. Postoperative serum HMGB1 and cholangitis could predict high recurrence and unfavorable prognosis.","Source":"PubMed","category":"HUMAN","training_data":"HMGB1 correlates with angiogenesis and poor prognosis of perihilar cholangiocarcinoma via elevating VEGFR2 of vessel endothelium Perihilar cholangiocarcinoma (PHCCA) is the most common type of cholangiocarcinoma with low resection rate and high morbidity. The study of PHCCA biomarkers made progresses slowly compared with intrahepatic cholangiocarcinoma because of surgical complexity and low possibility of radical surgery, which resulted in the difficulty of specimen obtainment. To screen and identify new biomarkers in PHCCA, we constructed a retrospective cohort with 121 PHCCA patients and a prospective cohort consisting of 64 PHCCA patients, and screened the candidate biomarkers by immunohistochemistry and quantified PCR. In our study, expression of high mobility group box 1 (HMGB1) was demonstrated to be significantly associated with microvascular density (MVD) and unfavorable prognosis of PHCCA in both retrospective and prospective study. Moreover, HMGB1 concentrations in bile and serum of PHCCA patients and healthy controls were detected and compared. Postoperative serum HMGB1 and reflux cholangitis indicated recurrence and unfavorable prognosis of PHCCA. With experiments in vitro and in vivo, we demonstrated that intracellular HMGB1 could be released from PHCCA cells and induce invasion and angiogenesis with LPS stimulation. VEGFR2 expression in vessel endothelial cells was upregulated by the released HMGB1 from PHCCA, resulting in the ectopic angiogenesis. In conclusion, intracellular HMGB1 could be released from PHCCA cells and promote angiogenesis via elevating VEGFR2 in vessel endothelial cells. High expression of HMGB1 was associated with MVD and poor prognosis in clinical analyzation. Postoperative serum HMGB1 and cholangitis could predict high recurrence and unfavorable prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"evaluation ajcc 8th edition staging system pathologically versus clinically staged intrahepatic cholangiocarcinoma icca time revisit dogma surveillance epidemiology end results seer analysis background recently ajcc released 8th edition changes staging system intrahepatic cholangiocarcinoma icca study sought validate proposed changes 8th edition ajcc system n classification icca using population based data set methods using surveillance epidemiology end results seer database 1998 2013 patients undergoing resection non surgical management non metastatic icca identified overall survival estimated using kaplan meier method compared using log rank tests concordance indices c indices calculated cox proportional hazards models calculated evaluate discriminatory power results study included 2630 patients resected 37 non surgically managed 63 icca nodal staging performed 56 31 positive nodes patients icca median 5 year survival ajcc classification t1a t1b t2 t3 t4 32 21 14 10 10 months respectively p 0 001 concordance index staging system 0 57 patients 0 62 underwent resection 0 54 patients undergo resection conclusion summary new ajcc 8th edition staging system comparable 7th edition valid stratifying patients icca however performance staging system better patients undergoing surgical resection undergoing non surgical management findings highlight need improved accuracy radiological imaging clinically staging patients guide prognosis pubmed","probabilities":0.9799733,"Title":"Evaluation of the AJCC 8th Edition Staging System for Pathologically Versus Clinically Staged Intrahepatic Cholangiocarcinoma (iCCA): a Time to Revisit a Dogma? A Surveillance, Epidemiology, and End Results (SEER) Analysis","Abstract":"BACKGROUND: Recently, the AJCC has released its 8th edition changes to the staging system for intrahepatic cholangiocarcinoma (iCCA). This study sought to validate the proposed changes to the 8th edition of AJCC system for T and N classification of iCCA using a population-based data set. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database (1998-2013), patients undergoing resection or non-surgical management for non-metastatic iCCA were identified. Overall survival was estimated using the Kaplan-Meier method and compared using log-rank tests. Concordance indices (c-indices) calculated from Cox proportional hazards models were calculated to evaluate discriminatory power. RESULTS: The study included 2630 patients resected (37%) or non-surgically managed (63%) for iCCA. Nodal staging was performed in 56%, of whom 31% had positive nodes. For all patients with iCCA, the median 5-year survival by AJCC T classification for T1a, T1b, T2, T3, and T4 was 32, 21, 14, 10, and 10 months, respectively (p < 0.001). The concordance index for the staging system was 0.57 for all patients, 0.62 for those who underwent resection, and 0.54 for patients who did not undergo resection. CONCLUSION: In summary, the new AJCC 8th edition staging system is comparable to the 7th edition and valid in stratifying patients with iCCA. However, the performance of the staging system is better in patients undergoing surgical resection than those undergoing non-surgical management. These findings further highlight the need for improved accuracy of radiological imaging in clinically staging patients to guide prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of the AJCC 8th Edition Staging System for Pathologically Versus Clinically Staged Intrahepatic Cholangiocarcinoma (iCCA): a Time to Revisit a Dogma? A Surveillance, Epidemiology, and End Results (SEER) Analysis BACKGROUND: Recently, the AJCC has released its 8th edition changes to the staging system for intrahepatic cholangiocarcinoma (iCCA). This study sought to validate the proposed changes to the 8th edition of AJCC system for T and N classification of iCCA using a population-based data set. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER) database (1998-2013), patients undergoing resection or non-surgical management for non-metastatic iCCA were identified. Overall survival was estimated using the Kaplan-Meier method and compared using log-rank tests. Concordance indices (c-indices) calculated from Cox proportional hazards models were calculated to evaluate discriminatory power. RESULTS: The study included 2630 patients resected (37%) or non-surgically managed (63%) for iCCA. Nodal staging was performed in 56%, of whom 31% had positive nodes. For all patients with iCCA, the median 5-year survival by AJCC T classification for T1a, T1b, T2, T3, and T4 was 32, 21, 14, 10, and 10 months, respectively (p < 0.001). The concordance index for the staging system was 0.57 for all patients, 0.62 for those who underwent resection, and 0.54 for patients who did not undergo resection. CONCLUSION: In summary, the new AJCC 8th edition staging system is comparable to the 7th edition and valid in stratifying patients with iCCA. However, the performance of the staging system is better in patients undergoing surgical resection than those undergoing non-surgical management. These findings further highlight the need for improved accuracy of radiological imaging in clinically staging patients to guide prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extrahepatic cancers chronic hcv infection infectious agents hcv account 15 human cancers hcv infects hepatocytes also extrahepatic cells chronic hcv infection induce chronic inflammation qualitative quantitative alterations immune repertoire tissue microenvironment induce various neoplasias epidemiological studies meta analyses suggest increased rate extrahepatic cancers patients chronic hcv infection along higher risk intrahepatic cholangiocarcinoma pancreatic cancer non hodgkin lymphoma nhl highlighting need screen hcv infection patients cancers development b cell nhl associated hcv infection relative risk 1 5 direct transformation related presence virus chronic antigenic stimulation two major non exclusive mechanisms involved hcv related lymphomagenesis hcv infection alters survival patients lymphoma sustained virologic response svr substantially improves prognosis antiviral treatments might induce remission indolent lymphoma svr achieved even without chemotherapy emphasizing role hcv lymphomagenesis context however studies needed provide prospective evidence causal relationship chronic hcv infection extrahepatic cancers determine whether risk extrahepatic cancers reduced svr review report recent studies analysing risk extrahepatic cancers associated chronic hcv infection although doubt regarding direct indirect causality hcv nhl increased risk cancers less clear exception cholangiocarcinoma pubmed","probabilities":0.962963,"Title":"Extrahepatic cancers and chronic HCV infection","Abstract":"Infectious agents, such as HCV, account for ∼15% of human cancers. HCV infects not only hepatocytes but also extrahepatic cells. Chronic HCV infection can induce chronic inflammation with qualitative and quantitative alterations of the immune repertoire and tissue microenvironment, which could induce various neoplasias. Epidemiological studies and meta-analyses suggest an increased rate of extrahepatic cancers in patients with chronic HCV infection along with a higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin lymphoma (NHL), highlighting the need to screen for HCV infection in patients with these cancers. Development of B cell NHL has been associated with HCV infection, with a relative risk of ∼1.5. Direct transformation related to the presence of the virus and chronic antigenic stimulation are the two major non-exclusive mechanisms involved in HCV-related lymphomagenesis. HCV infection alters survival of patients with lymphoma, and sustained virologic response (SVR) substantially improves prognosis. Antiviral treatments might induce remission of indolent lymphoma when SVR is achieved even without chemotherapy, emphasizing the role of HCV in lymphomagenesis in this context. However, studies are needed to provide prospective evidence of a causal relationship between chronic HCV infection and other extrahepatic cancers and to determine whether the risk of extrahepatic cancers is reduced with SVR. In this Review, we report on recent studies analysing the risk of extrahepatic cancers associated with chronic HCV infection. Although there is no doubt regarding the direct and indirect causality between HCV and NHL, an increased risk of other cancers is less clear, with the exception of cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Extrahepatic cancers and chronic HCV infection Infectious agents, such as HCV, account for ∼15% of human cancers. HCV infects not only hepatocytes but also extrahepatic cells. Chronic HCV infection can induce chronic inflammation with qualitative and quantitative alterations of the immune repertoire and tissue microenvironment, which could induce various neoplasias. Epidemiological studies and meta-analyses suggest an increased rate of extrahepatic cancers in patients with chronic HCV infection along with a higher risk of intrahepatic cholangiocarcinoma, pancreatic cancer and non-Hodgkin lymphoma (NHL), highlighting the need to screen for HCV infection in patients with these cancers. Development of B cell NHL has been associated with HCV infection, with a relative risk of ∼1.5. Direct transformation related to the presence of the virus and chronic antigenic stimulation are the two major non-exclusive mechanisms involved in HCV-related lymphomagenesis. HCV infection alters survival of patients with lymphoma, and sustained virologic response (SVR) substantially improves prognosis. Antiviral treatments might induce remission of indolent lymphoma when SVR is achieved even without chemotherapy, emphasizing the role of HCV in lymphomagenesis in this context. However, studies are needed to provide prospective evidence of a causal relationship between chronic HCV infection and other extrahepatic cancers and to determine whether the risk of extrahepatic cancers is reduced with SVR. In this Review, we report on recent studies analysing the risk of extrahepatic cancers associated with chronic HCV infection. Although there is no doubt regarding the direct and indirect causality between HCV and NHL, an increased risk of other cancers is less clear, with the exception of cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ercp guided radiofrequency ablation primary therapy inoperable ampullary carcinomas background endoscopic ablation duodenal ampullary malignancy fully assessed aims study aimed evaluate efficacy safety endoscopic retrograde cholangiopancreatograpy ercp guided radiofrequency ablation rfa inoperable ampullary cancer methods patients inoperable ampullary cancer underwent ercp guided rfa january 2012 august 2017 rf energy 7 10 w delivered using bipolar rfa electrodes endoscopic guidance rfas repeated every 1 3 months visible tumor eliminated patients followed till june 2018 biliary event noted managed endoscopically results twenty three patients underwent median two rfa sessions range 1 6 median interval 56 range 35 90 days among 18 78 3 patients received endoscopic re evaluations nine patients showed remaining lesion nine showed 50 tumor size reduction median follow duration 517 days range 60 1836 days eight 34 8 patients required endoscopic re interventions re intervention rate 6 months rfa 36 8 twelve patients alive among six required biliary stenting accumulative mean survival 1081 95 ci 757 8 1404 0 days rfa related adverse events occurred four cases 7 7 including mild pancreatitis 1 bleeding 1 late distal biliary stenosis 2 conclusion pilot study shows ercp guided rfa safe use able reduce tumor volume re interventions patients inoperable ampullary cancer stn","probabilities":0.9799733,"Title":"Ercp-Guided Radiofrequency Ablation As The Primary Therapy For Inoperable Ampullary Carcinomas","Abstract":"Background: Endoscopic ablation of duodenal ampullary malignancy has not been fully assessed. \r\n\r\n Aims: The study aimed to evaluate the efficacy and safety of Endoscopic retrograde cholangiopancreatograpy (ERCP)-guided radiofrequency ablation (RFA) for inoperable ampullary cancer. \r\n\r\n Methods: Patients with inoperable ampullary cancer underwent ERCP-guided RFA from January 2012 to August 2017. RF energy (7-10 W) was delivered using bipolar RFA electrodes under endoscopic guidance. RFAs were repeated every 1-3 months until visible tumor was eliminated. All patients were followed up till June 2018, during which any biliary event was noted and managed endoscopically. \r\n\r\n Results: Twenty-three patients underwent a median of two RFA sessions (range 1-6) at a median interval of 56 (range 35-90) days. Among 18 (78.3%) patients who received endoscopic re-evaluations, nine patients showed no remaining lesion and nine showed more than 50% tumor size reduction. During a median follow-up duration of 517 days (range 60-1836 days), eight (34.8%) patients required endoscopic re-interventions. The re-intervention rate at 6 months after RFA was 36.8%. Twelve patients were alive, among whom six required no biliary stenting. The accumulative mean survival was 1081 (95% CI 757.8-1404.0) days. RFA-related adverse events occurred in four cases (7.7%) including mild pancreatitis (1), bleeding (1), and late distal biliary stenosis (2). \r\n\r\n Conclusion: This pilot study shows that ERCP-guided RFA is safe to use and able to reduce tumor volume and re-interventions in patients with inoperable ampullary cancer.","Source":"STN","category":"HUMAN","training_data":"Ercp-Guided Radiofrequency Ablation As The Primary Therapy For Inoperable Ampullary Carcinomas Background: Endoscopic ablation of duodenal ampullary malignancy has not been fully assessed. \r\n\r\n Aims: The study aimed to evaluate the efficacy and safety of Endoscopic retrograde cholangiopancreatograpy (ERCP)-guided radiofrequency ablation (RFA) for inoperable ampullary cancer. \r\n\r\n Methods: Patients with inoperable ampullary cancer underwent ERCP-guided RFA from January 2012 to August 2017. RF energy (7-10 W) was delivered using bipolar RFA electrodes under endoscopic guidance. RFAs were repeated every 1-3 months until visible tumor was eliminated. All patients were followed up till June 2018, during which any biliary event was noted and managed endoscopically. \r\n\r\n Results: Twenty-three patients underwent a median of two RFA sessions (range 1-6) at a median interval of 56 (range 35-90) days. Among 18 (78.3%) patients who received endoscopic re-evaluations, nine patients showed no remaining lesion and nine showed more than 50% tumor size reduction. During a median follow-up duration of 517 days (range 60-1836 days), eight (34.8%) patients required endoscopic re-interventions. The re-intervention rate at 6 months after RFA was 36.8%. Twelve patients were alive, among whom six required no biliary stenting. The accumulative mean survival was 1081 (95% CI 757.8-1404.0) days. RFA-related adverse events occurred in four cases (7.7%) including mild pancreatitis (1), bleeding (1), and late distal biliary stenosis (2). \r\n\r\n Conclusion: This pilot study shows that ERCP-guided RFA is safe to use and able to reduce tumor volume and re-interventions in patients with inoperable ampullary cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"wide resection margin improves survival patients early intrahepatic cholangiocarcinoma 22 year single center experience objectives prognosis intrahepatic cholangiocarcinoma icc remained poor despite multitude advancement medical care resection margin status one modifiable factors surgeon possibly manipulate alter disease outcome however significance margin status margin width still controversial study serves elucidate role method retrospective cohort queen mary hospital university hong kong consecutive patients diagnosed icc surgical resection performed curative intent retrieved patients cholangiohepatocellular carcinoma klaskin tumour tumour extrahepatic bile duct uncertain tumour pathology excluded results 1991 2013 107 patients underwent hepatectomy icc gender predilection observed 58 males 49 females median age patients 61 median tumour size 6 cm 43 moderately differentiated adenocarcinoma clear resection margin achieved 95 patients 88 8 median margin width 0 5 cm hospital length stay operative mortality eleven days 3 respectively disease free survival overall survival 17 5 months 25 1 months respectively multivariate analysis showed margin width independent factor associated disease free survival p 0 015 95 c 0 4 0 9 sub group analysis patients solitary tumour showed margin width independent factor affecting overall survival p 0 048 0 577 95 ci 0 334 0 996 discriminant analysis showed overall survival increased 36 months 185 months margin width greater 0 9 cm p 0 025 patients solitary tumour conclusion aggressive resection achieve resection margin least 1 cm maximizes chance cure patients early icc google scholar","probabilities":0.9799733,"Title":"Wide Resection Margin Improves Survival In Patients With Early Intrahepatic Cholangiocarcinoma-A 22-Year Single Center Experience","Abstract":"Objectives\nPrognosis of Intrahepatic Cholangiocarcinoma (ICC) remained poor despite the multitude advancement of medical care. Resection margin status is one of the few modifiable factors that a surgeon could possibly manipulate to alter the disease outcome. However, the significance of margin status and margin width is still controversial. This study serves to further elucidate the role of them.\nMethod\nThis is a retrospective cohort from the Queen Mary Hospital, The University of Hong Kong. Consecutive patients diagnosed to have ICC and with surgical resection performed in curative intent were retrieved, while patients with cholangiohepatocellular carcinoma, Klaskin tumour, tumour of extrahepatic bile duct and uncertain tumour pathology were excluded.\nResults\nFrom 1991 to 2013, there were 107 patients underwent hepatectomy for ICC. Gender predilection was not observed with 58 males and 49 females, median age of the patients was 61. The median tumour size was 6 cm and most of them (43%) were moderately differentiated adenocarcinoma. Clear resection margin were achieved in 95 patients (88.8%) and the median margin width was 0.5 cm. The Hospital length of stay and operative mortality were eleven days and 3% respectively. The disease free survival and overall survival was 17.5 months and 25.1 months respectively. Multivariate analysis showed that margin width was an independent factor associated with disease free survival (P = 0.015, 95% C.I. 0.4–0.9). Sub-group analysis in patients with solitary tumour showed that margin width is an independent factor affecting overall survival (P = 0.048 OR 0.577 95% CI 0.334–0.996). Discriminant analysis showed that the overall survival increased from 36 months to 185 months when margin width was greater than 0.9 cm (p = 0.025) in patients with solitary tumour.\nConclusion\nAggressive resection to achieve resection margin of at least 1 cm maximizes chance of cure in patients with early ICC.","Source":"Google Scholar","category":"HUMAN","training_data":"Wide Resection Margin Improves Survival In Patients With Early Intrahepatic Cholangiocarcinoma-A 22-Year Single Center Experience Objectives\nPrognosis of Intrahepatic Cholangiocarcinoma (ICC) remained poor despite the multitude advancement of medical care. Resection margin status is one of the few modifiable factors that a surgeon could possibly manipulate to alter the disease outcome. However, the significance of margin status and margin width is still controversial. This study serves to further elucidate the role of them.\nMethod\nThis is a retrospective cohort from the Queen Mary Hospital, The University of Hong Kong. Consecutive patients diagnosed to have ICC and with surgical resection performed in curative intent were retrieved, while patients with cholangiohepatocellular carcinoma, Klaskin tumour, tumour of extrahepatic bile duct and uncertain tumour pathology were excluded.\nResults\nFrom 1991 to 2013, there were 107 patients underwent hepatectomy for ICC. Gender predilection was not observed with 58 males and 49 females, median age of the patients was 61. The median tumour size was 6 cm and most of them (43%) were moderately differentiated adenocarcinoma. Clear resection margin were achieved in 95 patients (88.8%) and the median margin width was 0.5 cm. The Hospital length of stay and operative mortality were eleven days and 3% respectively. The disease free survival and overall survival was 17.5 months and 25.1 months respectively. Multivariate analysis showed that margin width was an independent factor associated with disease free survival (P = 0.015, 95% C.I. 0.4–0.9). Sub-group analysis in patients with solitary tumour showed that margin width is an independent factor affecting overall survival (P = 0.048 OR 0.577 95% CI 0.334–0.996). Discriminant analysis showed that the overall survival increased from 36 months to 185 months when margin width was greater than 0.9 cm (p = 0.025) in patients with solitary tumour.\nConclusion\nAggressive resection to achieve resection margin of at least 1 cm maximizes chance of cure in patients with early ICC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"coming precision era staging systems intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma icc second common primary liver cancer appropriate treatment aggressive heterogeneous cancer requires accurate staging prognostic stratification patient selection clinical trials past two decades several staging systems prognostic models icc developed include independent prognostic factors tumor extent clinical parameters histopathological features inaccurate accumulating findings offer new insights genetic molecular basis icc progression hence staging systems prognostic models incorporate clinicalpathological factors molecular genomic information tumor biomarkers hence accurately estimate prognosis become reality review summarizes current staging systems prognostic models icc highlights need establish precise personalized systems models incorporate tumor biologic factors pubmed","probabilities":0.9799733,"Title":"Coming of a precision era of the staging systems for intrahepatic cholangiocarcinoma?","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Appropriate treatment of this aggressive and heterogeneous cancer requires accurate staging and prognostic stratification, as does patient selection for clinical trials. Over the past two decades, several staging systems and prognostic models for ICC have been developed. Most include independent prognostic factors such as tumor extent, clinical parameters and histopathological features and are inaccurate. Accumulating findings offer new insights into the genetic and molecular basis of ICC progression. Hence, staging systems and prognostic models that incorporate in clinicalpathological factors, molecular and genomic information, and tumor biomarkers, and hence more accurately estimate prognosis, will become a reality. This review summarizes the current staging systems and prognostic models for ICC and highlights the need to establish more precise and personalized systems and models that incorporate tumor biologic factors.","Source":"PubMed","category":"HUMAN","training_data":"Coming of a precision era of the staging systems for intrahepatic cholangiocarcinoma? Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer. Appropriate treatment of this aggressive and heterogeneous cancer requires accurate staging and prognostic stratification, as does patient selection for clinical trials. Over the past two decades, several staging systems and prognostic models for ICC have been developed. Most include independent prognostic factors such as tumor extent, clinical parameters and histopathological features and are inaccurate. Accumulating findings offer new insights into the genetic and molecular basis of ICC progression. Hence, staging systems and prognostic models that incorporate in clinicalpathological factors, molecular and genomic information, and tumor biomarkers, and hence more accurately estimate prognosis, will become a reality. This review summarizes the current staging systems and prognostic models for ICC and highlights the need to establish more precise and personalized systems and models that incorporate tumor biologic factors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"reappraisal hepatopancreatoduodenectomy treatment modality bile duct gallbladder cancer background hepatopancreatoduodenectomy performed achieve radical resection malignant biliary tumors reviewed clinical outcomes evaluate clinical feasibility hepatopancreatoduodenectomy treatment gallbladder bile duct cancer methods twenty three patients underwent hepatopancreatoduodenectomy 1995 2007 10 gallbladder cancer 13 bile duct cancer median follow periods 15 0 months results r0 resection performed 17 23 patients 73 9 morbidity mortality rates 91 3 13 0 respectively five year survival rates 10 0 gallbladder cancer 32 3 bile duct cancer survival 3 years possible patients stage iia less whereas gallbladder cancer patients stage iii bile duct cancer stage iib died within 2 years bile duct cancer patients pn0 survived longer pn1 p 0 001 conclusions obtain negative proximal distal ductal resection margins biliary tract cancer r0 resection long term survival achieved hepatopancreatoduodenectomy however adoption patients lymph node metastasis adjacent organ invasion recommended pubmed","probabilities":0.9799733,"Title":"Reappraisal of hepatopancreatoduodenectomy as a treatment modality for bile duct and gallbladder cancer","Abstract":"BACKGROUND: Hepatopancreatoduodenectomy has been performed to achieve radical resection in malignant biliary tumors. We reviewed clinical outcomes to evaluate the clinical feasibility of hepatopancreatoduodenectomy for the treatment of gallbladder and bile duct cancer. METHODS: Twenty-three patients underwent hepatopancreatoduodenectomy from 1995 to 2007; 10 gallbladder cancer and 13 bile duct cancer. Median follow-up periods were 15.0 months. RESULTS: R0 resection was performed in 17 of 23 patients (73.9%). Morbidity and mortality rates were 91.3% and 13.0%, respectively. Five-year survival rates were 10.0% for gallbladder cancer and 32.3% for bile duct cancer. Survival more than 3 years was possible for most patients with stage IIA or less, whereas all gallbladder cancer patients with stage III and all bile duct cancer with stage IIB or more died within 2 years. Bile duct cancer patients with pN0 survived longer than those with pN1 (p < 0.001). CONCLUSIONS: To obtain negative proximal and distal ductal resection margins in the biliary tract cancer, R0 resection and long-term survival can be achieved by hepatopancreatoduodenectomy. However, its adoption in patients with lymph node metastasis or adjacent organ invasion cannot be recommended.","Source":"PubMed","category":"HUMAN","training_data":"Reappraisal of hepatopancreatoduodenectomy as a treatment modality for bile duct and gallbladder cancer BACKGROUND: Hepatopancreatoduodenectomy has been performed to achieve radical resection in malignant biliary tumors. We reviewed clinical outcomes to evaluate the clinical feasibility of hepatopancreatoduodenectomy for the treatment of gallbladder and bile duct cancer. METHODS: Twenty-three patients underwent hepatopancreatoduodenectomy from 1995 to 2007; 10 gallbladder cancer and 13 bile duct cancer. Median follow-up periods were 15.0 months. RESULTS: R0 resection was performed in 17 of 23 patients (73.9%). Morbidity and mortality rates were 91.3% and 13.0%, respectively. Five-year survival rates were 10.0% for gallbladder cancer and 32.3% for bile duct cancer. Survival more than 3 years was possible for most patients with stage IIA or less, whereas all gallbladder cancer patients with stage III and all bile duct cancer with stage IIB or more died within 2 years. Bile duct cancer patients with pN0 survived longer than those with pN1 (p < 0.001). CONCLUSIONS: To obtain negative proximal and distal ductal resection margins in the biliary tract cancer, R0 resection and long-term survival can be achieved by hepatopancreatoduodenectomy. However, its adoption in patients with lymph node metastasis or adjacent organ invasion cannot be recommended. PubMed","prediction_labels":"HUMAN"},{"cleaned":"genetic alteration regulated micrornas biliary tract cancers biliary tract cancers btcs constitute relatively rare highly malignant class tumors poor prognosis including gallbladder cancer intra extra hepatic cholangiocarcinoma recently accumulated evidences demonstrated deregulated expression micrornas mirnas closely associated development invasion metastasis prognosis different cancers including btcs mirnas comprise endogenously expressed highly evolutionarily conserved group small non coding single stranded rnas negatively regulate target genes expression means combining 3 untranslated region utr corresponding mrnas post transcriptional level significant roles various fundamental cellular procedures including cell proliferation differentiation migration cell cycle control apoptosis recent studies indicated mirnas function novel tumor promoting genes tumor suppressor genes act potential therapeutic targets anticancer treatment genetic alteration regulated mirnas result tumorigenesis tumor inhibition anomalous mirnas expression patterns acting phenotypic signatures distinct cancers promising used diagnostic prognostic predictive biomarkers review summarize current findings studies potential genetic alteration regulated mirnas roles btcs pubmed","probabilities":0.962963,"Title":"Genetic alteration regulated by microRNAs in biliary tract cancers","Abstract":"Biliary tract cancers (BTCs) constitute a relatively rare but highly malignant class of tumors with poor prognosis including gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma. Recently, accumulated evidences have demonstrated that deregulated expression of microRNAs (miRNAs) is closely associated with the development, invasion, metastasis and prognosis of different cancers including BTCs. MiRNAs comprise an endogenously expressed and highly evolutionarily conserved group of small, non-coding, single-stranded RNAs which negatively regulate target genes expression by means of combining with 3' untranslated region (UTR) of corresponding mRNAs at the post-transcriptional level with significant roles in various fundamental cellular procedures including cell proliferation, differentiation, migration, cell cycle control and apoptosis. Recent studies have indicated that miRNAs could function as novel tumor-promoting genes or tumor suppressor genes to act as potential therapeutic targets in anticancer treatment because the genetic alteration regulated by miRNAs could result in tumorigenesis and tumor inhibition. Anomalous miRNAs expression patterns, acting as phenotypic signatures of distinct cancers, are promising to be used as diagnostic, prognostic, predictive biomarkers. In this review, we summarize the current findings from the studies about potential genetic alteration regulated by miRNAs and their roles in BTCs.","Source":"PubMed","category":"HUMAN","training_data":"Genetic alteration regulated by microRNAs in biliary tract cancers Biliary tract cancers (BTCs) constitute a relatively rare but highly malignant class of tumors with poor prognosis including gallbladder cancer, intra- and extra-hepatic cholangiocarcinoma. Recently, accumulated evidences have demonstrated that deregulated expression of microRNAs (miRNAs) is closely associated with the development, invasion, metastasis and prognosis of different cancers including BTCs. MiRNAs comprise an endogenously expressed and highly evolutionarily conserved group of small, non-coding, single-stranded RNAs which negatively regulate target genes expression by means of combining with 3' untranslated region (UTR) of corresponding mRNAs at the post-transcriptional level with significant roles in various fundamental cellular procedures including cell proliferation, differentiation, migration, cell cycle control and apoptosis. Recent studies have indicated that miRNAs could function as novel tumor-promoting genes or tumor suppressor genes to act as potential therapeutic targets in anticancer treatment because the genetic alteration regulated by miRNAs could result in tumorigenesis and tumor inhibition. Anomalous miRNAs expression patterns, acting as phenotypic signatures of distinct cancers, are promising to be used as diagnostic, prognostic, predictive biomarkers. In this review, we summarize the current findings from the studies about potential genetic alteration regulated by miRNAs and their roles in BTCs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"relationship cumulative exposure 12 dichloropropane incidence risk cholangiocarcinoma among offset printing workers objectives study aimed evaluate relationship cumulative exposure 1 2 dichloropropane 1 2 dcp incidence risk cholangiocarcinoma among workers offset proof printing section small printing company osaka japan methods identified 95 workers printing company 78 men 17 women exposed 1 2 dcp 1987 2006 calculated standardised incidence ratio sir cholangiocarcinoma 1987 2012 estimated cumulative exposure 1 2 dcp calculated sirs four exposure categories also calculated incidence rate ratios rrs adjusted sex age calendar year dichloromethane dcm exposure three exposure categories using poisson regression analysis results cumulative exposures 1 2 dcp ranged 32 3433 ppm years mean 851 ppm years sir 1171 95 ci 682 1875 analysis four exposure categories sirs increased significantly three highest exposure categories lowest category adjusted rrs middle high exposure categories 14 9 95 ci 4 1 54 3 17 1 95 ci 3 8 76 2 respectively analysis without lag time 11 4 95 ci 3 3 39 6 32 4 95 ci 6 4 163 9 respectively analysis 5 year lag trend analysis revealed significant increase rr association increasing cumulative exposure 1 2 dcp dcm exposure significantly associated development cholangiocarcinoma conclusions present study demonstrated exposure response relationship exposure 1 2 dcp development cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Relationship Between Cumulative Exposure To 12-Dichloropropane And Incidence Risk Of Cholangiocarcinoma Among Offset Printing Workers","Abstract":"Objectives: This study aimed to evaluate the relationship between cumulative exposure to 1,2-dichloropropane (1,2-DCP) and incidence risk of cholangiocarcinoma among workers in the offset proof-printing section of a small printing company in Osaka, Japan. \r\n\r\n Methods: We identified 95 workers of a printing company (78 men and 17 women) who had been exposed to 1,2-DCP between 1987 and 2006, and calculated the standardised incidence ratio (SIR) of cholangiocarcinoma from 1987 to 2012. We estimated cumulative exposure to 1,2-DCP and calculated SIRs in four exposure categories. We also calculated incidence rate ratios (RRs) adjusted by sex, age, calendar year and dichloromethane (DCM) exposure for three exposure categories using Poisson regression analysis. \r\n\r\n Results: Cumulative exposures to 1,2-DCP ranged from 32 to 3433 ppm-years (mean, 851 ppm-years) and the SIR was 1171 (95% CI 682 to 1875). In the analysis of the four exposure categories, SIRs increased significantly in the three highest exposure categories, but not in the lowest category. Adjusted RRs in the middle and high exposure categories were 14.9 (95% CI 4.1 to 54.3) and 17.1 (95% CI 3.8 to 76.2), respectively, in the analysis without lag time, and were 11.4 (95% CI 3.3 to 39.6) and 32.4 (95% CI 6.4 to 163.9), respectively, in the analysis with a 5-year lag. The trend analysis revealed a significant increase in RR in association with increasing cumulative exposure to 1,2-DCP. DCM exposure was not significantly associated with the development of cholangiocarcinoma. \r\n\r\n Conclusions: The present study demonstrated an exposure-response relationship between exposure to 1,2-DCP and the development of cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Relationship Between Cumulative Exposure To 12-Dichloropropane And Incidence Risk Of Cholangiocarcinoma Among Offset Printing Workers Objectives: This study aimed to evaluate the relationship between cumulative exposure to 1,2-dichloropropane (1,2-DCP) and incidence risk of cholangiocarcinoma among workers in the offset proof-printing section of a small printing company in Osaka, Japan. \r\n\r\n Methods: We identified 95 workers of a printing company (78 men and 17 women) who had been exposed to 1,2-DCP between 1987 and 2006, and calculated the standardised incidence ratio (SIR) of cholangiocarcinoma from 1987 to 2012. We estimated cumulative exposure to 1,2-DCP and calculated SIRs in four exposure categories. We also calculated incidence rate ratios (RRs) adjusted by sex, age, calendar year and dichloromethane (DCM) exposure for three exposure categories using Poisson regression analysis. \r\n\r\n Results: Cumulative exposures to 1,2-DCP ranged from 32 to 3433 ppm-years (mean, 851 ppm-years) and the SIR was 1171 (95% CI 682 to 1875). In the analysis of the four exposure categories, SIRs increased significantly in the three highest exposure categories, but not in the lowest category. Adjusted RRs in the middle and high exposure categories were 14.9 (95% CI 4.1 to 54.3) and 17.1 (95% CI 3.8 to 76.2), respectively, in the analysis without lag time, and were 11.4 (95% CI 3.3 to 39.6) and 32.4 (95% CI 6.4 to 163.9), respectively, in the analysis with a 5-year lag. The trend analysis revealed a significant increase in RR in association with increasing cumulative exposure to 1,2-DCP. DCM exposure was not significantly associated with the development of cholangiocarcinoma. \r\n\r\n Conclusions: The present study demonstrated an exposure-response relationship between exposure to 1,2-DCP and the development of cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"proteomic analysis reveals important role 14 3 3s anoikis resistance cholangiocarcinoma cells cholangiocarcinoma cca high prevalence cancer thailand highly metastatic high mortality rates anoikis resistance ability cells survive detachment extracellular matrix necessary property metastatic cancer report differential protein expression anoikis resistant cca cell line culture attachment conditions compared nonattachment conditions studied using 2de coupled protein identification lc ms ms data reveal deregulation proteins involved stress response cytoskeleton rearrangement proapoptosis cell proliferation glycolysis interestingly 14 3 3 14 3 3 sigma protein intensely upregulated detached cca cells real time rt pcr analysis confirmed sigma isotype abundant transcript among 14 3 3 genes cca cells furthermore silencing 14 3 3 expression small interfering rna cca cells resulted significantly increased percentage cell death detached culture findings provide first evidence showing 14 3 3 protein plays crucial role anoikis resistance cca cells therefore 14 3 3 might potential target cca therapy stn","probabilities":0.9467213,"Title":"Proteomic Analysis Reveals Important Role Of 14-3-3S In Anoikis Resistance Of Cholangiocarcinoma Cells","Abstract":"Cholangiocarcinoma (CCA), a high-prevalence cancer in Thailand, is highly metastatic and has high mortality rates. Anoikis resistance or the ability of cells to survive after detachment from extracellular matrix is a necessary property of metastatic cancer. Here, we report differential protein expression of an anoikis-resistant CCA cell line culture, under attachment conditions compared to nonattachment conditions, studied using 2DE coupled with protein identification by LC-MS/MS. Our data reveal the deregulation of proteins involved in stress response, cytoskeleton rearrangement, proapoptosis, cell proliferation, and glycolysis. Interestingly, 14-3-3σ (14-3-3 sigma) protein was intensely upregulated in detached CCA cells. Real-time RT-PCR analysis confirmed that only the sigma isotype was the most abundant transcript among 14-3-3 genes in CCA cells. Furthermore, silencing 14-3-3σ expression by small interfering RNA in CCA cells resulted in significantly increased percentage of cell death in detached culture. Our findings provide the first evidence showing that 14-3-3σ protein plays a crucial role in anoikis resistance of CCA cells. Therefore, 14-3-3σ might be a potential target in CCA therapy.","Source":"STN","category":"ANIMAL","training_data":"Proteomic Analysis Reveals Important Role Of 14-3-3S In Anoikis Resistance Of Cholangiocarcinoma Cells Cholangiocarcinoma (CCA), a high-prevalence cancer in Thailand, is highly metastatic and has high mortality rates. Anoikis resistance or the ability of cells to survive after detachment from extracellular matrix is a necessary property of metastatic cancer. Here, we report differential protein expression of an anoikis-resistant CCA cell line culture, under attachment conditions compared to nonattachment conditions, studied using 2DE coupled with protein identification by LC-MS/MS. Our data reveal the deregulation of proteins involved in stress response, cytoskeleton rearrangement, proapoptosis, cell proliferation, and glycolysis. Interestingly, 14-3-3σ (14-3-3 sigma) protein was intensely upregulated in detached CCA cells. Real-time RT-PCR analysis confirmed that only the sigma isotype was the most abundant transcript among 14-3-3 genes in CCA cells. Furthermore, silencing 14-3-3σ expression by small interfering RNA in CCA cells resulted in significantly increased percentage of cell death in detached culture. Our findings provide the first evidence showing that 14-3-3σ protein plays a crucial role in anoikis resistance of CCA cells. Therefore, 14-3-3σ might be a potential target in CCA therapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"improvement clinical outcomes patients gallbladder cancer lessons periodic comparison tertiary referral center background current guidelines gallbladder cancer gbc contain controversies reported survival improvement gbc 20 years study designed explore chronologic change survival outcomes gbc prognostic factors methods clinicopathologic features survival outcomes analyzed 692 consecutive gbc patients underwent surgery 1987 2014 including 255 treated period p 1 1987 2000 437 p2 2001 2014 results mean age 63 3 years curative resection rate 59 2 5 year survival rate 5 ysr curative resection 67 1 comparisons p1 p2 showed mean age asymptomatic presentation extended cholecystectomy curative resection adjuvant chemotherapy tumor t2 significantly higher p2 overall 5 ysr curative surgery significantly lower p1 patients underwent curative resection poor prognostic factors included symptomatic presentation ca 19 9 37 iu ml poor differentiation tumor t3 lymph nodal involvement patients received non curative surgery well moderately differentiated tumor adjuvant chemotherapy provide survival benefit conclusions detection gbc early stage optimal curative surgery may improve survival outcomes gbc chemotherapy provides survival benefit palliative setting pubmed","probabilities":0.9799733,"Title":"Improvement of clinical outcomes in the patients with gallbladder cancer: lessons from periodic comparison in a tertiary referral center","Abstract":"BACKGROUND: Current guidelines for gallbladder cancer (GBC) contain controversies and some reported no survival improvement in GBC during 20 years. This study was designed to explore the chronologic change of survival outcomes in GBC and prognostic factors. METHODS: Clinicopathologic features and survival outcomes were analyzed in 692 consecutive GBC patients who underwent surgery between 1987 and 2014, including 255 treated in Period (P) 1 (1987-2000) and 437 in P2 (2001-2014). RESULTS: The mean age was 63.3 years. Curative resection rate was 59.2% and 5-year survival rate (5-YSR) after curative resection was 67.1%. Comparisons between P1 and P2 showed that mean age, asymptomatic presentation, extended cholecystectomy, curative resection, adjuvant chemotherapy, and tumor ≤ T2 were significantly higher during P2. The overall 5-YSR after curative surgery was significantly lower in P1. In patients who underwent curative resection, poor prognostic factors included symptomatic presentation, CA 19-9 >37 IU/ml, poor differentiation, tumor ≥ T3, and lymph nodal involvement. In patients who received non-curative surgery, well- or moderately differentiated tumor and adjuvant chemotherapy provide survival benefit. CONCLUSIONS: Detection of GBC at an early stage and optimal curative surgery may improve survival outcomes in GBC. Chemotherapy provides survival benefit in palliative setting.","Source":"PubMed","category":"HUMAN","training_data":"Improvement of clinical outcomes in the patients with gallbladder cancer: lessons from periodic comparison in a tertiary referral center BACKGROUND: Current guidelines for gallbladder cancer (GBC) contain controversies and some reported no survival improvement in GBC during 20 years. This study was designed to explore the chronologic change of survival outcomes in GBC and prognostic factors. METHODS: Clinicopathologic features and survival outcomes were analyzed in 692 consecutive GBC patients who underwent surgery between 1987 and 2014, including 255 treated in Period (P) 1 (1987-2000) and 437 in P2 (2001-2014). RESULTS: The mean age was 63.3 years. Curative resection rate was 59.2% and 5-year survival rate (5-YSR) after curative resection was 67.1%. Comparisons between P1 and P2 showed that mean age, asymptomatic presentation, extended cholecystectomy, curative resection, adjuvant chemotherapy, and tumor ≤ T2 were significantly higher during P2. The overall 5-YSR after curative surgery was significantly lower in P1. In patients who underwent curative resection, poor prognostic factors included symptomatic presentation, CA 19-9 >37 IU/ml, poor differentiation, tumor ≥ T3, and lymph nodal involvement. In patients who received non-curative surgery, well- or moderately differentiated tumor and adjuvant chemotherapy provide survival benefit. CONCLUSIONS: Detection of GBC at an early stage and optimal curative surgery may improve survival outcomes in GBC. Chemotherapy provides survival benefit in palliative setting. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder carcinoma poor prognosis related late age presentation introduction mean age diagnosis incidental gallbladder cancer igc increasing time purpose study reassess igc cohort regarding implemented treatments especially investigating late age burden potential therapeutic options materials methods 7841 cholecystectomies performed single center 2002 2013 retrospectively collected patients igc identified demographics type surgery stage survival morbidity mortality analyzed results 49 patients 0 62 igc 63 female 18 male average age diagnosis 76 years 10 patients t1a 11 t1b 16 t2 8 t3 4 t4 none t1a patients reoperated tumor recurrence latest follow 11 39 patients 28 advanced stage suitable surgery siv b sv bisegmentectomy without major bile duct resection carried radical surgery precluded mainly late age comorbidities 16 patients 5 patients unresectable 4 refused surgery 3 lost follow t1b t2 patients recurrence radical resection conclusions igc presented late age cohort spread 11 year period series reported average age diagnosis lower 70 years majority patients receive stepwise surgical approach due age related issues refused surgery late age subsequent radical resection provided excellent outcomes submitted surgery early stages google scholar","probabilities":0.9799733,"Title":"Incidental Gallbladder Carcinoma Is Poor Prognosis Related To Late Age Of Presentation?","Abstract":"Introduction: Mean age at diagnosis for incidental gallbladder cancer (IGC) has been increasing over time. Purpose of our study was to reassess our IGC cohort regarding implemented treatments, especially investigating the late age burden over potential therapeutic options.\nMaterials and methods: 7841 cholecystectomies performed in a single center between 2002 and 2013 were retrospectively collected. Patients with IGC were identified and demographics, type of surgery, stage, survival, morbidity and mortality were analyzed.\nResults: 49 patients (0.62%) had IGC (63% female, 18% male). Average age at diagnosis was 76 years. 10 patients were T1a, 11 were T1b, 16 were T2, 8 were T3 and 4 were T4. None of the T1a patients was reoperated or had tumor recurrence at the latest follow-up. Only 11 of 39 patients (28%) with advanced stage were suitable for surgery and SIV b + SV bisegmentectomy with or without major bile duct resection was carried out. Radical surgery was precluded mainly for late age and comorbidities\n(16 patients), 5 patients were unresectable, 4 refused surgery and 3 were lost during follow-up.\nT1b and T2 patients had no recurrence after radical resection.\nConclusions: IGC presented at late age in our cohort, spread over an 11-year period. Most series reported an average age at diagnosis lower than 70 years. The majority of patients did not receive a stepwise surgical approach due to age-related issues or because they refused surgery for late age. Subsequent radical resection provided excellent outcomes for those submitted to surgery at early stages.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidental Gallbladder Carcinoma Is Poor Prognosis Related To Late Age Of Presentation? Introduction: Mean age at diagnosis for incidental gallbladder cancer (IGC) has been increasing over time. Purpose of our study was to reassess our IGC cohort regarding implemented treatments, especially investigating the late age burden over potential therapeutic options.\nMaterials and methods: 7841 cholecystectomies performed in a single center between 2002 and 2013 were retrospectively collected. Patients with IGC were identified and demographics, type of surgery, stage, survival, morbidity and mortality were analyzed.\nResults: 49 patients (0.62%) had IGC (63% female, 18% male). Average age at diagnosis was 76 years. 10 patients were T1a, 11 were T1b, 16 were T2, 8 were T3 and 4 were T4. None of the T1a patients was reoperated or had tumor recurrence at the latest follow-up. Only 11 of 39 patients (28%) with advanced stage were suitable for surgery and SIV b + SV bisegmentectomy with or without major bile duct resection was carried out. Radical surgery was precluded mainly for late age and comorbidities\n(16 patients), 5 patients were unresectable, 4 refused surgery and 3 were lost during follow-up.\nT1b and T2 patients had no recurrence after radical resection.\nConclusions: IGC presented at late age in our cohort, spread over an 11-year period. Most series reported an average age at diagnosis lower than 70 years. The majority of patients did not receive a stepwise surgical approach due to age-related issues or because they refused surgery for late age. Subsequent radical resection provided excellent outcomes for those submitted to surgery at early stages. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"survival analysis intrahepatic cholangiocarcinoma resection background intrahepatic cholangiocarcinoma icc second common primary hepatic malignancy studies outcome resection icc rare aim study elucidate outcomes prognostic factors icc patients undergoing hepatic resection methods retrospective study conducted total 63 patients underwent surgical resection curative intent icc performed survival analysis preoperative postoperative clinicopathologic factors according clinical outcome results cumulative 1 3 5 year survival rates 68 2 50 5 31 8 respectively univariate analysis revealed patient old age high preoperative carbohydrate antigen 19 9 ca19 9 level major vessel invasion classification lymph node metastasis lymphatic invasion perineural invasion intrahepatic metastasis narrow resection margin statistically significant multivariate analysis patient old age high preoperative ca19 9 level lymphatic invasion narrow resection margin independent dismal prognostic factors preoperative ca19 9 level shows significant correlation histopathologic factors including major vessel invasion bile duct invasion perineural invasion conclusions preoperative ca19 9 level valuable clinical factor predicting histopathologic invasiveness well clinical outcome adequate resection margin modifiable factor surgeon hepatic resection icc pubmed","probabilities":0.9799733,"Title":"Survival analysis of intrahepatic cholangiocarcinoma after resection","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, but the studies for the outcome after resection of ICC are rare. The aim of this study was to elucidate outcomes and prognostic factors of ICC in patients undergoing hepatic resection. METHODS: A retrospective study was conducted with a total of 63 patients who underwent surgical resection with curative intent for ICC. We performed the survival analysis with preoperative and postoperative clinicopathologic factors according to the clinical outcome. RESULTS: The cumulative 1-, 3-, and 5-year survival rates were 68.2, 50.5, and 31.8%, respectively. Univariate analysis revealed that patient's old age, high preoperative carbohydrate antigen 19-9 (CA19-9) level, major vessel invasion, T classification, lymph node metastasis, lymphatic invasion, perineural invasion, intrahepatic metastasis, and narrow resection margin were statistically significant. By multivariate analysis, patient's old age, high preoperative CA19-9 level, lymphatic invasion, and narrow resection margin were independent dismal prognostic factors. The preoperative CA19-9 level shows a significant correlation with some histopathologic factors including major vessel invasion, bile duct invasion, and perineural invasion. CONCLUSIONS: Preoperative CA19-9 level was a valuable clinical factor for predicting histopathologic invasiveness as well as clinical outcome. An adequate resection margin was the only modifiable factor by a surgeon during hepatic resection for ICC.","Source":"PubMed","category":"HUMAN","training_data":"Survival analysis of intrahepatic cholangiocarcinoma after resection BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary hepatic malignancy, but the studies for the outcome after resection of ICC are rare. The aim of this study was to elucidate outcomes and prognostic factors of ICC in patients undergoing hepatic resection. METHODS: A retrospective study was conducted with a total of 63 patients who underwent surgical resection with curative intent for ICC. We performed the survival analysis with preoperative and postoperative clinicopathologic factors according to the clinical outcome. RESULTS: The cumulative 1-, 3-, and 5-year survival rates were 68.2, 50.5, and 31.8%, respectively. Univariate analysis revealed that patient's old age, high preoperative carbohydrate antigen 19-9 (CA19-9) level, major vessel invasion, T classification, lymph node metastasis, lymphatic invasion, perineural invasion, intrahepatic metastasis, and narrow resection margin were statistically significant. By multivariate analysis, patient's old age, high preoperative CA19-9 level, lymphatic invasion, and narrow resection margin were independent dismal prognostic factors. The preoperative CA19-9 level shows a significant correlation with some histopathologic factors including major vessel invasion, bile duct invasion, and perineural invasion. CONCLUSIONS: Preoperative CA19-9 level was a valuable clinical factor for predicting histopathologic invasiveness as well as clinical outcome. An adequate resection margin was the only modifiable factor by a surgeon during hepatic resection for ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"scalp recurrence cholangiocarcinoma curative hepatectomy report two cases cholangiocarcinomas second common primary liver malignancies lymphatics common route metastatic spread cholangiocarcinomas frequent sites metastasis liver abdominal lymph nodes peritoneum lungs cutaneous metastasis cholangiocarcinoma rare commonly occurs following percutaneous biliary drainage brain skull metastases tumor uncommon however rare metastatic lesions may occasionally first disease manifestation although scalp recurrence following curative treatment uncommon herein present cases two patients cholangiocarcinoma evaluated resectable based criteria cholangiocarcinoma resectability developed scalp recurrence following curative hepatectomy therefore although scalp recurrence rare occurrence following curative treatment cholangiocarcinoma metastases included differential diagnosis stn","probabilities":0.9799733,"Title":"Scalp Recurrence Of Cholangiocarcinoma After Curative Hepatectomy: A Report Of Two Cases","Abstract":"Cholangiocarcinomas are the second most common primary liver malignancies. The lymphatics are the common route of metastatic spread for cholangiocarcinomas. The most frequent sites of metastasis are the liver, abdominal lymph nodes, peritoneum and lungs. Cutaneous metastasis of cholangiocarcinoma is rare, and most commonly occurs following percutaneous biliary drainage. Brain or skull metastases from this tumor are uncommon. However, these rare metastatic lesions may occasionally be the first disease manifestation, although scalp recurrence following curative treatment is uncommon. We herein present the cases of two patients with cholangiocarcinoma, who were evaluated as resectable based on the criteria for cholangiocarcinoma resectability, and developed scalp recurrence following curative hepatectomy. Therefore, although scalp recurrence is a rare occurrence following curative treatment for cholangiocarcinoma, metastases should be included in the differential diagnosis.","Source":"STN","category":"ANIMAL","training_data":"Scalp Recurrence Of Cholangiocarcinoma After Curative Hepatectomy: A Report Of Two Cases Cholangiocarcinomas are the second most common primary liver malignancies. The lymphatics are the common route of metastatic spread for cholangiocarcinomas. The most frequent sites of metastasis are the liver, abdominal lymph nodes, peritoneum and lungs. Cutaneous metastasis of cholangiocarcinoma is rare, and most commonly occurs following percutaneous biliary drainage. Brain or skull metastases from this tumor are uncommon. However, these rare metastatic lesions may occasionally be the first disease manifestation, although scalp recurrence following curative treatment is uncommon. We herein present the cases of two patients with cholangiocarcinoma, who were evaluated as resectable based on the criteria for cholangiocarcinoma resectability, and developed scalp recurrence following curative hepatectomy. Therefore, although scalp recurrence is a rare occurrence following curative treatment for cholangiocarcinoma, metastases should be included in the differential diagnosis. STN","prediction_labels":"HUMAN"},{"cleaned":"pd l1 pd 1 expression correlate prognosis extrahepatic cholangiocarcinoma present study aimed investigate clinicopathological significance programmed cell death ligand 1 pd l1 programmed cell death protein 1 pd 1 expression extrahepatic cholangiocarcinoma ecc pd l1 pd 1 expression detected immunohistochemical methods 70 ecc formalin fixed paraffin embedded tissue specimens 50 para carcinoma tissue specimens associations pd l1 pd 1 expression clinicopathological characteristics prognosis ecc patients explored positive rates pd l1 pd 1 expression increased ecc tissues compared corresponding para carcinoma tissues besides expression pd l1 correlated expression pd 1 p 0 05 statistical analysis revealed expression pd l1 pd 1 ecc tissues exhibited correlation patient age sex histological grade significantly correlated tumor node metastasis tnm stage lymphatic metastasis univariate analysis demonstrated pd l1 expression pd 1 expression tnm stage lymphatic metastasis significantly associated survival time patients multivariate analysis revealed pd l1 expression independent prognostic factor patients ecc preliminary results suggested pd l1 pd 1 immunodetection may valuable prognostic marker ecc patients pd l1 immunodetection may used independent factor evaluate prognosis ecc patients google scholar","probabilities":0.9467213,"Title":"Pd-L1 And Pd-1 Expression Correlate With Prognosis In Extrahepatic Cholangiocarcinoma","Abstract":"The present study aimed to investigate the clinicopathological significance of programmed cell death ligand-1 (PD-L1) and programmed cell death protein 1 (PD-1) expression in extrahepatic cholangiocarcinoma (ECC). PD-L1 and PD-1 expression was detected by immunohistochemical methods in 70 ECC formalin-fixed, paraffin-embedded tissue specimens and 50 para-carcinoma tissue specimens. The associations of PD-L1 and PD-1 expression with clinicopathological characteristics and prognosis of ECC patients were explored. Positive rates of PD-L1 and PD-1 expression were increased in ECC tissues compared with those in the corresponding para-carcinoma tissues. Besides, the expression of PD-L1 was correlated with the expression of PD-1 (P<0.05). Statistical analysis revealed that the expression of PD-L1 and PD-1 in ECC tissues exhibited no correlation with patient age, sex or histological grade, but was significantly correlated with tumor-node-metastasis (TNM) stage and lymphatic metastasis. Univariate analysis demonstrated that PD-L1 expression, PD-1 expression, TNM stage and lymphatic metastasis were significantly associated with the survival time of patients. Further multivariate analysis revealed the PD-L1 expression was an independent prognostic factor of patients with ECC. These preliminary results suggested that PD-L1 or PD-1 immunodetection may be a valuable prognostic marker for ECC patients, and that PD-L1 immunodetection may be used as an independent factor to evaluate the prognosis of ECC patients.","Source":"Google Scholar","category":"ANIMAL","training_data":"Pd-L1 And Pd-1 Expression Correlate With Prognosis In Extrahepatic Cholangiocarcinoma The present study aimed to investigate the clinicopathological significance of programmed cell death ligand-1 (PD-L1) and programmed cell death protein 1 (PD-1) expression in extrahepatic cholangiocarcinoma (ECC). PD-L1 and PD-1 expression was detected by immunohistochemical methods in 70 ECC formalin-fixed, paraffin-embedded tissue specimens and 50 para-carcinoma tissue specimens. The associations of PD-L1 and PD-1 expression with clinicopathological characteristics and prognosis of ECC patients were explored. Positive rates of PD-L1 and PD-1 expression were increased in ECC tissues compared with those in the corresponding para-carcinoma tissues. Besides, the expression of PD-L1 was correlated with the expression of PD-1 (P<0.05). Statistical analysis revealed that the expression of PD-L1 and PD-1 in ECC tissues exhibited no correlation with patient age, sex or histological grade, but was significantly correlated with tumor-node-metastasis (TNM) stage and lymphatic metastasis. Univariate analysis demonstrated that PD-L1 expression, PD-1 expression, TNM stage and lymphatic metastasis were significantly associated with the survival time of patients. Further multivariate analysis revealed the PD-L1 expression was an independent prognostic factor of patients with ECC. These preliminary results suggested that PD-L1 or PD-1 immunodetection may be a valuable prognostic marker for ECC patients, and that PD-L1 immunodetection may be used as an independent factor to evaluate the prognosis of ECC patients. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"prevalence management gallbladder cancer tertiary hpb center abstract available google scholar","probabilities":0.9799733,"Title":"Prevalence And Management Of Gallbladder Cancer In A Tertiary Hpb Center","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Prevalence And Management Of Gallbladder Cancer In A Tertiary Hpb Center Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"estimating survival benefit adjuvant therapy based bayesian network prediction model curatively resected advanced gallbladder adenocarcinoma background factors affecting prognosis role adjuvant therapy advanced gallbladder carcinoma gbc curative resection remain unclear aim provide survival prediction model patients gbc well identify role adjuvant therapy methods patients curatively resected advanced gallbladder adenocarcinoma t3 t4 selected surveillance epidemiology end results database 2004 2015 survival prediction model based bayesian network bn constructed using tree augmented na ve bayes algorithm composite importance measures applied rank influence factors survival dataset divided training dataset establish bn model testing dataset test model randomly ratio 7 3 confusion matrix receiver operating characteristic curve used evaluate model accuracy results total 818 patients met inclusion criteria median survival time 9 0 mo accuracy bn model 69 67 area curve value testing dataset 77 72 adjuvant radiation adjuvant chemotherapy ctx stage scope regional lymph node surgery radiation sequence ranked top five prognostic factors survival prediction table established based stage n stage adjuvant radiotherapy xrt ctx distribution survival time 9 0 mo affected different treatments order adjuvant chemoradiotherapy cxrt adjuvant radiation adjuvant chemotherapy surgery alone patients node positive disease larger benefit predicted model adjuvant chemoradiotherapy survival analysis showed significant difference among different adjuvant therapy groups log rank surgery alone vs ctx p 0 001 surgery alone vs xrt p 0 014 surgery alone vs cxrt p 0 001 conclusion bn based survival prediction model used decision making support tool advanced gbc patients adjuvant chemoradiotherapy expected improve survival significantly patients node positive disease pubmed","probabilities":0.9799733,"Title":"Estimating survival benefit of adjuvant therapy based on a Bayesian network prediction model in curatively resected advanced gallbladder adenocarcinoma","Abstract":"BACKGROUND: The factors affecting the prognosis and role of adjuvant therapy in advanced gallbladder carcinoma (GBC) after curative resection remain unclear. AIM: To provide a survival prediction model to patients with GBC as well as to identify the role of adjuvant therapy. METHODS: Patients with curatively resected advanced gallbladder adenocarcinoma (T3 and T4) were selected from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. A survival prediction model based on Bayesian network (BN) was constructed using the tree-augmented naïve Bayes algorithm, and composite importance measures were applied to rank the influence of factors on survival. The dataset was divided into a training dataset to establish the BN model and a testing dataset to test the model randomly at a ratio of 7:3. The confusion matrix and receiver operating characteristic curve were used to evaluate the model accuracy. RESULTS: A total of 818 patients met the inclusion criteria. The median survival time was 9.0 mo. The accuracy of BN model was 69.67%, and the area under the curve value for the testing dataset was 77.72%. Adjuvant radiation, adjuvant chemotherapy (CTx), T stage, scope of regional lymph node surgery, and radiation sequence were ranked as the top five prognostic factors. A survival prediction table was established based on T stage, N stage, adjuvant radiotherapy (XRT), and CTx. The distribution of the survival time (>9.0 mo) was affected by different treatments with the order of adjuvant chemoradiotherapy (cXRT) > adjuvant radiation > adjuvant chemotherapy > surgery alone. For patients with node-positive disease, the larger benefit predicted by the model is adjuvant chemoradiotherapy. The survival analysis showed that there was a significant difference among the different adjuvant therapy groups (log rank, surgery alone vs CTx, P < 0.001; surgery alone vs XRT, P = 0.014; surgery alone vs cXRT, P < 0.001). CONCLUSION: The BN-based survival prediction model can be used as a decision-making support tool for advanced GBC patients. Adjuvant chemoradiotherapy is expected to improve the survival significantly for patients with node-positive disease.","Source":"PubMed","category":"HUMAN","training_data":"Estimating survival benefit of adjuvant therapy based on a Bayesian network prediction model in curatively resected advanced gallbladder adenocarcinoma BACKGROUND: The factors affecting the prognosis and role of adjuvant therapy in advanced gallbladder carcinoma (GBC) after curative resection remain unclear. AIM: To provide a survival prediction model to patients with GBC as well as to identify the role of adjuvant therapy. METHODS: Patients with curatively resected advanced gallbladder adenocarcinoma (T3 and T4) were selected from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. A survival prediction model based on Bayesian network (BN) was constructed using the tree-augmented naïve Bayes algorithm, and composite importance measures were applied to rank the influence of factors on survival. The dataset was divided into a training dataset to establish the BN model and a testing dataset to test the model randomly at a ratio of 7:3. The confusion matrix and receiver operating characteristic curve were used to evaluate the model accuracy. RESULTS: A total of 818 patients met the inclusion criteria. The median survival time was 9.0 mo. The accuracy of BN model was 69.67%, and the area under the curve value for the testing dataset was 77.72%. Adjuvant radiation, adjuvant chemotherapy (CTx), T stage, scope of regional lymph node surgery, and radiation sequence were ranked as the top five prognostic factors. A survival prediction table was established based on T stage, N stage, adjuvant radiotherapy (XRT), and CTx. The distribution of the survival time (>9.0 mo) was affected by different treatments with the order of adjuvant chemoradiotherapy (cXRT) > adjuvant radiation > adjuvant chemotherapy > surgery alone. For patients with node-positive disease, the larger benefit predicted by the model is adjuvant chemoradiotherapy. The survival analysis showed that there was a significant difference among the different adjuvant therapy groups (log rank, surgery alone vs CTx, P < 0.001; surgery alone vs XRT, P = 0.014; surgery alone vs cXRT, P < 0.001). CONCLUSION: The BN-based survival prediction model can be used as a decision-making support tool for advanced GBC patients. Adjuvant chemoradiotherapy is expected to improve the survival significantly for patients with node-positive disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"positive cystic duct margin index cholecystectomy incidental gallbladder cancer important negative prognosticator background prognostic factors following index cholecystectomy patients incidental gallbladder cancer igbc poorly understood aim study assess value initial cystic duct margin status prognosticator factor aid clinical decision making move forward curative intent oncologic extended resection oer methods retrospective study included patients igbc underwent subsequent oer curative intent 2 centers usa chile 1999 2016 patients without evidence residual cancer rc oer included pathologic features examined predictors overall survival os analyzed results study included 179 patients thirty three patients 17 positive cystic duct margin index cholecystectomy forty two patients 23 underwent resection common bile duct os significantly worse patients positive cystic duct margin index cholecystectomy os rates 5 years 34 vs 57 p 0 032 following multivariate analysis positive cystic duct margin index cholecystectomy predictive worse os patients evidence residual cancer rc oer hazard ratio 1 7 95 ci 1 04 2 78 p 0 034 conclusions positive cystic duct margin index cholecystectomy strong independent predictor worse os even cancer found oer patients positive cystic duct margin rc oer common bile duct resection leads improved outcomes stn","probabilities":0.9799733,"Title":"Positive Cystic Duct Margin At Index Cholecystectomy In Incidental Gallbladder Cancer Is An Important Negative Prognosticator","Abstract":"Background: Prognostic factors following index-cholecystectomy in patients with incidental gallbladder cancer (IGBC) are poorly understood. The aim of this study was to assess the value of the initial cystic duct margin status as a prognosticator factor and to aid in clinical decision making to move forward with curative intent oncologic extended resection (OER). \r\n\r\n Methods: This retrospective study included patients with IGBC who underwent subsequent OER with curative intent at 2 centers (USA and Chile) between 1999 and 2016., Patients with and without evidence of residual cancer (RC) at OER were included. Pathologic features were examined, and predictors of overall survival (OS) were analyzed. \r\n\r\n Results: The study included 179 patients. Thirty-three patients (17%) had a positive cystic duct margin at the index cholecystectomy. Forty-two patients (23%) underwent resection of the common bile duct. OS was significantly worse in the patients with a positive cystic duct margin at index cholecystectomy (OS rates at 5 years, 34% vs 57%; p = 0.032). Following multivariate analysis, only a positive cystic duct margin at index cholecystectomy was predictive of worse OS in patients with no evidence of residual cancer (RC) at OER (hazard ratio, 1.7 95%CI 1.04-2.78; p = 0.034). \r\n\r\n Conclusions: A positive cystic duct margin at index-cholecystectomy is a strong independent predictor of worse OS even if no further cancer is found at OER. In patients with positive cystic duct margin and no RC at OER common bile duct resection leads to improved outcomes.","Source":"STN","category":"HUMAN","training_data":"Positive Cystic Duct Margin At Index Cholecystectomy In Incidental Gallbladder Cancer Is An Important Negative Prognosticator Background: Prognostic factors following index-cholecystectomy in patients with incidental gallbladder cancer (IGBC) are poorly understood. The aim of this study was to assess the value of the initial cystic duct margin status as a prognosticator factor and to aid in clinical decision making to move forward with curative intent oncologic extended resection (OER). \r\n\r\n Methods: This retrospective study included patients with IGBC who underwent subsequent OER with curative intent at 2 centers (USA and Chile) between 1999 and 2016., Patients with and without evidence of residual cancer (RC) at OER were included. Pathologic features were examined, and predictors of overall survival (OS) were analyzed. \r\n\r\n Results: The study included 179 patients. Thirty-three patients (17%) had a positive cystic duct margin at the index cholecystectomy. Forty-two patients (23%) underwent resection of the common bile duct. OS was significantly worse in the patients with a positive cystic duct margin at index cholecystectomy (OS rates at 5 years, 34% vs 57%; p = 0.032). Following multivariate analysis, only a positive cystic duct margin at index cholecystectomy was predictive of worse OS in patients with no evidence of residual cancer (RC) at OER (hazard ratio, 1.7 95%CI 1.04-2.78; p = 0.034). \r\n\r\n Conclusions: A positive cystic duct margin at index-cholecystectomy is a strong independent predictor of worse OS even if no further cancer is found at OER. In patients with positive cystic duct margin and no RC at OER common bile duct resection leads to improved outcomes. STN","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological features cct2 pdia2 expression gallbladder squamous adenosquamous carcinoma gallbladder adenocarcinoma background gallbladder cancer gbc relatively uncommon carcinoma among gastrointestinal cancers usually rather poor prognosis common subtype gbc adenocarcinoma ac accounts 90 gbc squamous carcinoma adenosquamous carcinoma sc asc comparatively rare histopathological subtypes gbc clinicopathological features biological behaviors sc asc well characterized molecular biomarkers currently available predicting progression metastasis prognosis sc asc subtype gbc methods examined expression levels cct2 pdia3 immunohistochemistry ihc staining human gbc tissue samples collected 46 patients sc asc evaluated clinicopathological significance cct2 pdia3 expression sc asc subtypes gbc kaplan meier analysis multivariate cox regression analysis comparison included specimens 80 ac patients study investigate specificity cct2 pdia3 expression gbc subtypes results found positive expression cct2 pdia3 significantly associated clinicopathological features sc asc ac specimens including high tnm stage lymph node metastasis univariate analysis revealed two year survival rate significantly lower patients positive expression cct2 pdia3 negative expression multivariate analysis also indicated positive expression cct2 pdia3 negatively correlated poor postoperative patient survival positively correlated high mortality conclusions study suggests positive expression cct2 pdia3 associated tumor progression clinical behavior gallbladder carcinoma therefore cct2 pdia3 potentially important diagnostic prognostic biomarkers sc asc ac subtypes gbc pubmed","probabilities":0.8684211,"Title":"Clinicopathological features and CCT2 and PDIA2 expression in gallbladder squamous/adenosquamous carcinoma and gallbladder adenocarcinoma","Abstract":"BACKGROUND: Gallbladder cancer (GBC) is a relatively uncommon carcinoma among gastrointestinal cancers and usually has a rather poor prognosis. The most common subtype of GBC is adenocarcinoma (AC), which accounts for about 90% of GBC. Squamous carcinoma/adenosquamous carcinoma (SC/ASC) are comparatively rare histopathological subtypes of GBC. The clinicopathological features and biological behaviors of SC/ASC have not been well-characterized. No molecular biomarkers are currently available for predicting the progression, metastasis, and prognosis of the SC/ASC subtype of GBC. METHODS: We examined the expression levels of CCT2 and PDIA3 by immunohistochemistry (IHC) staining in human GBC tissue samples collected from 46 patients with SC/ASC and evaluated the clinicopathological significance of both CCT2 and PDIA3 expression in the SC/ASC subtypes of GBC by Kaplan-Meier analysis and multivariate Cox regression analysis. For comparison, we included specimens from 80 AC patients in our study to investigate the specificity of CCT2 and PDIA3 expression in GBC subtypes. RESULTS: We found that the positive expression of CCT2 and PDIA3 was significantly associated with clinicopathological features of both SC/ASC and AC specimens, including high TNM stage and lymph node metastasis. Univariate analysis revealed that the two-year survival rate was significantly lower for patients with positive expression of CCT2 and PDIA3 than for those with negative expression. Multivariate analysis also indicated that the positive expression of CCT2 and PDIA3 was negatively correlated with poor postoperative patient survival and positively correlated with high mortality. CONCLUSIONS: Our study suggests that positive expression of CCT2 or PDIA3 is associated with tumor progression and the clinical behavior of gallbladder carcinoma. Therefore, CCT2 and PDIA3 could be potentially important diagnostic and prognostic biomarkers for both SC/ASC and AC subtypes of GBC.","Source":"PubMed","category":"ANIMAL","training_data":"Clinicopathological features and CCT2 and PDIA2 expression in gallbladder squamous/adenosquamous carcinoma and gallbladder adenocarcinoma BACKGROUND: Gallbladder cancer (GBC) is a relatively uncommon carcinoma among gastrointestinal cancers and usually has a rather poor prognosis. The most common subtype of GBC is adenocarcinoma (AC), which accounts for about 90% of GBC. Squamous carcinoma/adenosquamous carcinoma (SC/ASC) are comparatively rare histopathological subtypes of GBC. The clinicopathological features and biological behaviors of SC/ASC have not been well-characterized. No molecular biomarkers are currently available for predicting the progression, metastasis, and prognosis of the SC/ASC subtype of GBC. METHODS: We examined the expression levels of CCT2 and PDIA3 by immunohistochemistry (IHC) staining in human GBC tissue samples collected from 46 patients with SC/ASC and evaluated the clinicopathological significance of both CCT2 and PDIA3 expression in the SC/ASC subtypes of GBC by Kaplan-Meier analysis and multivariate Cox regression analysis. For comparison, we included specimens from 80 AC patients in our study to investigate the specificity of CCT2 and PDIA3 expression in GBC subtypes. RESULTS: We found that the positive expression of CCT2 and PDIA3 was significantly associated with clinicopathological features of both SC/ASC and AC specimens, including high TNM stage and lymph node metastasis. Univariate analysis revealed that the two-year survival rate was significantly lower for patients with positive expression of CCT2 and PDIA3 than for those with negative expression. Multivariate analysis also indicated that the positive expression of CCT2 and PDIA3 was negatively correlated with poor postoperative patient survival and positively correlated with high mortality. CONCLUSIONS: Our study suggests that positive expression of CCT2 or PDIA3 is associated with tumor progression and the clinical behavior of gallbladder carcinoma. Therefore, CCT2 and PDIA3 could be potentially important diagnostic and prognostic biomarkers for both SC/ASC and AC subtypes of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"adequate extent radical re resection incidental gallbladder carcinoma analysis german registry background complete surgical resection potentially curative treatment gallbladder cancer gallbladder carcinoma suspected preoperatively 30 patients 70 incidentally discovered pathologist incidental gallbladder carcinoma igbc igbc detected postoperatively re resection including liver resection lymph node dissection t2 tumor cases advanced stages recommended remains unclear whether prognosis wedge resection 2 3 cm margin gallbladder bed resection segments ivb v methods german registry founded 1997 aims prospectively record igbc cases germany study patients radical re resection treated according s3 guidelines germany aim study clarify whether different techniques liver re resection show comparable results differ depending tumor stage igbc patients n 624 results significant survival advantage patients early re resection observed trend better survival t1 tumor stage patients undergo less radical re resection especially wedge resection technique 3 cm gallbladder bed t2 tumor stage patients tendency better survival ivb v resection technique compared 3 cm wedge resection gallbladder bed significant survival benefit two techniques compared less radical resection evident t3 tumor cases showed better survival radical resection techniques conclusions wedge resection technique combined lymph node dissection may surgical strategy choice t1 tumor cases t2 tumors ivb v resection combined lymph node dissection hepatoduodenal ligament appears minimum volume resection required radical procedures needed tumors infiltrating serosa beyond pubmed","probabilities":0.9799733,"Title":"Adequate extent in radical re-resection of incidental gallbladder carcinoma: analysis of the German Registry","Abstract":"BACKGROUND: Complete surgical resection is the only potentially curative treatment of gallbladder cancer. Gallbladder carcinoma is suspected preoperatively in 30% of patients, and 70% are incidentally discovered by the pathologist (incidental gallbladder carcinoma, IGBC). If IGBC is detected postoperatively, a re-resection, including liver resection and lymph node dissection, in T2 tumor cases and more advanced stages is recommended. It remains unclear whether the prognosis of wedge resection (2-3-cm margin) of the gallbladder bed is the same as that of resection of segments IVb/V. METHODS: The German Registry, founded in 1997, aims to prospectively record all IGBC cases in Germany. In this study patients with a radical re-resection were treated according to the S3 Guidelines in Germany. The aim of this study was to clarify whether different techniques of liver re-resection show comparable results or if they differ depending on the tumor stage in IGBC patients (n = 624). RESULTS: A significant survival advantage in patients who have an early re-resection was observed. There was a trend of better survival in T1 tumor stage patients who undergo the less radical re-resection, especially the wedge-resection technique of 3 cm in the gallbladder bed. In T2 tumor stage patients there is a tendency for better survival with the IVb/V-resection technique compared to the 3-cm wedge resection in the gallbladder bed, and a significant survival benefit for these two techniques compared to less radical resection was evident. T3 tumor cases showed better survival with the more radical resection techniques. CONCLUSIONS: The wedge-resection technique combined with lymph node dissection may be the surgical strategy of choice in T1 tumor cases. For T2 tumors, IVb/V resection combined with lymph node dissection of the hepatoduodenal ligament appears to be the minimum volume of resection required. More radical procedures are needed for tumors infiltrating the serosa or beyond.","Source":"PubMed","category":"HUMAN","training_data":"Adequate extent in radical re-resection of incidental gallbladder carcinoma: analysis of the German Registry BACKGROUND: Complete surgical resection is the only potentially curative treatment of gallbladder cancer. Gallbladder carcinoma is suspected preoperatively in 30% of patients, and 70% are incidentally discovered by the pathologist (incidental gallbladder carcinoma, IGBC). If IGBC is detected postoperatively, a re-resection, including liver resection and lymph node dissection, in T2 tumor cases and more advanced stages is recommended. It remains unclear whether the prognosis of wedge resection (2-3-cm margin) of the gallbladder bed is the same as that of resection of segments IVb/V. METHODS: The German Registry, founded in 1997, aims to prospectively record all IGBC cases in Germany. In this study patients with a radical re-resection were treated according to the S3 Guidelines in Germany. The aim of this study was to clarify whether different techniques of liver re-resection show comparable results or if they differ depending on the tumor stage in IGBC patients (n = 624). RESULTS: A significant survival advantage in patients who have an early re-resection was observed. There was a trend of better survival in T1 tumor stage patients who undergo the less radical re-resection, especially the wedge-resection technique of 3 cm in the gallbladder bed. In T2 tumor stage patients there is a tendency for better survival with the IVb/V-resection technique compared to the 3-cm wedge resection in the gallbladder bed, and a significant survival benefit for these two techniques compared to less radical resection was evident. T3 tumor cases showed better survival with the more radical resection techniques. CONCLUSIONS: The wedge-resection technique combined with lymph node dissection may be the surgical strategy of choice in T1 tumor cases. For T2 tumors, IVb/V resection combined with lymph node dissection of the hepatoduodenal ligament appears to be the minimum volume of resection required. More radical procedures are needed for tumors infiltrating the serosa or beyond. PubMed","prediction_labels":"HUMAN"},{"cleaned":"genetic factors pathogenesis cholangiocarcinoma background cholangiocarcinoma cc increasing incidence pathogenesis remains poorly understood chronic inflammation bile duct cholestasis major risk factors cases west sporadic genetic polymorphisms biliary transporter proteins implicated benign biliary disease case progressive familial cholestasis associated childhood onset cc current study five biologically plausible candidate genes investigated abcb11 bsep abcb4 mdr3 abcc2 mrp2 atp8b1 fic1 nr1h4 fxr methods dna collected 172 caucasian individuals confirmed cc control cohort healthy caucasians formed seventy three snps selected using hapmap database capture genetic variation around five candidate loci genotyping undertaken competitive pcr based system confirmation hardy weinberg equilibrium cochran armitage trend testing performed using plink haplotype frequencies compared using haplo stats results 73 snps hardy weinberg equilibrium four snps abcb11 associated altered susceptibility cc including v444a polymorphism associations retain statistical significance bonferroni correction multiple testing haplotype analysis genotyped snps atp8b1 identified significant differences frequencies cases controls global p value 0 005 conclusion haplotypes atp8b1 demonstrated significant difference cc control groups trend towards significant association v444a cc given biological plausibility polymorphisms abcb11 atp8b1 risk modifiers cc study validation cohort required pubmed","probabilities":0.9799733,"Title":"Genetic factors in the pathogenesis of cholangiocarcinoma","Abstract":"BACKGROUND: Cholangiocarcinoma (CC) is increasing in incidence, but its pathogenesis remains poorly understood. Chronic inflammation of the bile duct and cholestasis are major risk factors, but most cases in the West are sporadic. Genetic polymorphisms in biliary transporter proteins have been implicated in benign biliary disease and, in the case of progressive familial cholestasis, have been associated with childhood onset of CC. In the current study, five biologically plausible candidate genes were investigated: ABCB11 (BSEP), ABCB4 (MDR3), ABCC2 (MRP2), ATP8B1 (FIC1) and NR1H4 (FXR). METHODS: DNA was collected from 172 Caucasian individuals with confirmed CC. A control cohort of healthy Caucasians was formed. Seventy-three SNPs were selected using the HapMap database to capture genetic variation around the five candidate loci. Genotyping was undertaken with a competitive PCR-based system. Confirmation of Hardy-Weinberg equilibrium and Cochran-Armitage trend testing were performed using PLINK. Haplotype frequencies were compared using haplo.stats. RESULTS: All 73 SNPs were in Hardy-Weinberg equilibrium. Four SNPs in ABCB11 were associated with altered susceptibility to CC, including the V444A polymorphism, but these associations did not retain statistical significance after Bonferroni correction for multiple testing. Haplotype analysis of the genotyped SNPs in ATP8B1 identified significant differences in frequencies between cases and controls (global p value of 0.005). CONCLUSION: Haplotypes in ATP8B1 demonstrated a significant difference between CC and control groups. There was a trend towards significant association of V444A with CC. Given the biological plausibility of polymorphisms in ABCB11 and ATP8B1 as risk modifiers for CC, further study in a validation cohort is required.","Source":"PubMed","category":"HUMAN","training_data":"Genetic factors in the pathogenesis of cholangiocarcinoma BACKGROUND: Cholangiocarcinoma (CC) is increasing in incidence, but its pathogenesis remains poorly understood. Chronic inflammation of the bile duct and cholestasis are major risk factors, but most cases in the West are sporadic. Genetic polymorphisms in biliary transporter proteins have been implicated in benign biliary disease and, in the case of progressive familial cholestasis, have been associated with childhood onset of CC. In the current study, five biologically plausible candidate genes were investigated: ABCB11 (BSEP), ABCB4 (MDR3), ABCC2 (MRP2), ATP8B1 (FIC1) and NR1H4 (FXR). METHODS: DNA was collected from 172 Caucasian individuals with confirmed CC. A control cohort of healthy Caucasians was formed. Seventy-three SNPs were selected using the HapMap database to capture genetic variation around the five candidate loci. Genotyping was undertaken with a competitive PCR-based system. Confirmation of Hardy-Weinberg equilibrium and Cochran-Armitage trend testing were performed using PLINK. Haplotype frequencies were compared using haplo.stats. RESULTS: All 73 SNPs were in Hardy-Weinberg equilibrium. Four SNPs in ABCB11 were associated with altered susceptibility to CC, including the V444A polymorphism, but these associations did not retain statistical significance after Bonferroni correction for multiple testing. Haplotype analysis of the genotyped SNPs in ATP8B1 identified significant differences in frequencies between cases and controls (global p value of 0.005). CONCLUSION: Haplotypes in ATP8B1 demonstrated a significant difference between CC and control groups. There was a trend towards significant association of V444A with CC. Given the biological plausibility of polymorphisms in ABCB11 and ATP8B1 as risk modifiers for CC, further study in a validation cohort is required. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical resection lymph node positive intrahepatic cholangiocarcinoma may improve survival background nodal positivity predictor poor survival following resection intrahepatic cholangiocarcinoma icc aim study evaluate impact surgical resection survival patients lymph node ln positive icc methods augmented version surveillance epidemiology end results program database utilized identify patients ln positive icc without distant metastases 2000 2014 patients stratified treatment chemotherapy alone surgical resection without chemotherapy survival evaluated using kaplan meier cox proportional hazard models results 169 patients underwent treatment ln positive icc identified 88 underwent surgical resection 12 underwent chemotherapy alone median survival patients underwent surgical resection different patients treated chemotherapy alone 19 months 95 confidence interval ci 17 33 versus 20 months ci 10 27 p 0 323 cox proportional hazard ratio model demonstrated black race associated worse survival p 0 05 surgical resection independently associated survival conclusion surgical resection patients ln positive icc may improve survival compared chemotherapy alone pathologic ln evaluation performed prior surgical resection improve patient selection ensure receipt optimal therapy pubmed","probabilities":0.9799733,"Title":"Surgical resection of lymph node positive intrahepatic cholangiocarcinoma may not improve survival","Abstract":"BACKGROUND: Nodal positivity is a predictor of poor survival following resection for intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the impact of surgical resection on survival in patients with lymph node (LN) positive ICC. METHODS: An augmented version of the Surveillance, Epidemiology, and End Results program database was utilized to identify patients with LN-positive ICC without distant metastases from 2000 to 2014. Patients were stratified by treatment: chemotherapy alone or surgical resection with/without chemotherapy. Survival was evaluated using Kaplan-Meier and Cox proportional hazard models. RESULTS: 169 patients who underwent treatment for LN-positive ICC were identified. 88% underwent surgical resection and 12% underwent chemotherapy alone. The median survival for patients who underwent surgical resection was not different from patients treated with chemotherapy alone (19 months 95% Confidence Interval (CI) 17-33 versus 20 months CI 10-27, p = 0.323). A cox-proportional hazard ratio model demonstrated that black race was associated with worse survival (p < 0.05), while surgical resection was not independently associated with survival. CONCLUSION: Surgical resection for patients with LN-positive ICC may not improve survival compared to chemotherapy alone. Pathologic LN evaluation should be performed prior to surgical resection, to improve patient selection and ensure receipt of optimal therapy.","Source":"PubMed","category":"HUMAN","training_data":"Surgical resection of lymph node positive intrahepatic cholangiocarcinoma may not improve survival BACKGROUND: Nodal positivity is a predictor of poor survival following resection for intrahepatic cholangiocarcinoma (ICC). The aim of this study was to evaluate the impact of surgical resection on survival in patients with lymph node (LN) positive ICC. METHODS: An augmented version of the Surveillance, Epidemiology, and End Results program database was utilized to identify patients with LN-positive ICC without distant metastases from 2000 to 2014. Patients were stratified by treatment: chemotherapy alone or surgical resection with/without chemotherapy. Survival was evaluated using Kaplan-Meier and Cox proportional hazard models. RESULTS: 169 patients who underwent treatment for LN-positive ICC were identified. 88% underwent surgical resection and 12% underwent chemotherapy alone. The median survival for patients who underwent surgical resection was not different from patients treated with chemotherapy alone (19 months 95% Confidence Interval (CI) 17-33 versus 20 months CI 10-27, p = 0.323). A cox-proportional hazard ratio model demonstrated that black race was associated with worse survival (p < 0.05), while surgical resection was not independently associated with survival. CONCLUSION: Surgical resection for patients with LN-positive ICC may not improve survival compared to chemotherapy alone. Pathologic LN evaluation should be performed prior to surgical resection, to improve patient selection and ensure receipt of optimal therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"arterial hyperenhancement small intrahepatic cholangiocarcinomas correlates microvessel counts patient survival background compare outcomes patients arterially hyperenhancing intrahepatic cholangiocarcinomas icc arterially hypoenhancing iccs partial hepatectomy cohort analysis prognostic factors methods june 2009 october 2011 prospective cohort 68 patients single resectable iccs 5 cm diameter underwent gadolinium contrast enhanced dynamic phase magnetic resonance imaging treated partial hepatectomy patients divided arterially hyperenhancing iccs n 28 arterially hypoenhancing iccs n 40 clinic radiologic pathologic results survival patients compared statistically analyzed results median overall survival os time significantly longer arterially hyperenhancing iccs 56 8 vs 37 0 months p 0 044 pathologic evaluation arterially hyperenhancing iccs showed significantly higher microvessel count mvc arterially hypoenhancing iccs 106 2 47 5 vs 46 9 21 6 mm2 p 0 001 arterial enhancement iccs found independent prognostic factor longer survival conclusion presence arterially hyperenhancing iccs related higher mvc exhibit better os time arterially hypoenhancing iccs partial hepatectomy stn","probabilities":0.9799733,"Title":"Arterial Hyperenhancement Of Small Intrahepatic Cholangiocarcinomas Correlates With Microvessel Counts And Patient Survival","Abstract":"Background: To compare outcomes of patients with arterially hyperenhancing intrahepatic cholangiocarcinomas (ICC) and arterially hypoenhancing ICCs after partial hepatectomy in a cohort with an analysis of prognostic factors. \r\n\r\n Methods: From June 2009 to October 2011, a prospective cohort of 68 patients with single resectable ICCs (≤5 cm in diameter) underwent gadolinium contrast-enhanced dynamic-phase magnetic resonance imaging and were treated with partial hepatectomy. Patients were divided into those with arterially hyperenhancing ICCs (n = 28) or arterially hypoenhancing ICCs (n = 40). Clinic-radiologic-pathologic results and survival of these patients were compared and statistically analyzed. \r\n\r\n Results: The median overall survival (OS) time was significantly longer in the arterially hyperenhancing ICCs (56.8 vs. 37.0 months) (p = 0.044). At pathologic evaluation, arterially hyperenhancing ICCs showed significantly higher microvessel count (MVC) than arterially hypoenhancing ICCs (106.2 ± 47.5 vs. 46.9 ± 21.6/mm2, p = 0.001). Arterial enhancement of ICCs was found to be an independent prognostic factor for longer survival. \r\n\r\n Conclusion: The presence of arterially hyperenhancing ICCs is related to higher MVC and exhibit a better OS time than arterially hypoenhancing ICCs after partial hepatectomy.","Source":"STN","category":"HUMAN","training_data":"Arterial Hyperenhancement Of Small Intrahepatic Cholangiocarcinomas Correlates With Microvessel Counts And Patient Survival Background: To compare outcomes of patients with arterially hyperenhancing intrahepatic cholangiocarcinomas (ICC) and arterially hypoenhancing ICCs after partial hepatectomy in a cohort with an analysis of prognostic factors. \r\n\r\n Methods: From June 2009 to October 2011, a prospective cohort of 68 patients with single resectable ICCs (≤5 cm in diameter) underwent gadolinium contrast-enhanced dynamic-phase magnetic resonance imaging and were treated with partial hepatectomy. Patients were divided into those with arterially hyperenhancing ICCs (n = 28) or arterially hypoenhancing ICCs (n = 40). Clinic-radiologic-pathologic results and survival of these patients were compared and statistically analyzed. \r\n\r\n Results: The median overall survival (OS) time was significantly longer in the arterially hyperenhancing ICCs (56.8 vs. 37.0 months) (p = 0.044). At pathologic evaluation, arterially hyperenhancing ICCs showed significantly higher microvessel count (MVC) than arterially hypoenhancing ICCs (106.2 ± 47.5 vs. 46.9 ± 21.6/mm2, p = 0.001). Arterial enhancement of ICCs was found to be an independent prognostic factor for longer survival. \r\n\r\n Conclusion: The presence of arterially hyperenhancing ICCs is related to higher MVC and exhibit a better OS time than arterially hypoenhancing ICCs after partial hepatectomy. STN","prediction_labels":"HUMAN"},{"cleaned":"evaluating american college surgeons national surgical improvement project risk calculator extrahepatic biliary malignancy results us extrahepatic biliary malignancy consortium objective assess accuracy acs nsqip calculator estimating risk operation gallbladder cancer extrahepatic cholangiocarcinoma methods adult patients gallbladder cancer distal hilar cholangiocarcinoma underwent curative intent complete resection january 2000 december 2014 included ability nsqip calculator accurately predict particular outcome assessed using c statistic 0 7 score reasonable models brier score zero score perfect models results 854 adult patients included commonly performed procedures included right left hepatic lobectomy 254 29 7 pancreaticoduodenectomy 132 15 5 trisegmentectomy 118 13 8 185 patients experienced surgical site infection ssi 21 7 median predicted risk 9 6 range 1 9 36 6 2 1 mortality median predicted risk 0 5 range 0 19 4 57 6 7 reoperations median predicted risk 3 3 range 0 9 13 2 169 19 7 patients readmitted median predicted risk 9 1 range 2 6 32 2 median length stay cohort 8 days range 0 119 days median predicted length stay 6 5 days range 2 5 25 5 days c statistics ssi mortality reoperation readmission 0 64 0 74 0 68 0 57 brier scores 0 17 0 02 0 06 0 16 respectively figure conclusion acs nsqip risk calculator estimates risk mortality reasonably well patients gallbladder extrahepatic biliary malignancy generally underestimates risk several postoperative complications future modifications calculator patient populations needed widespread use tool encouraged google scholar","probabilities":0.9799733,"Title":"Evaluating The American College Of Surgeons National Surgical Improvement Project Risk Calculator In Extrahepatic Biliary Malignancy: Results From The Us Extrahepatic Biliary Malignancy Consortium","Abstract":"Objective: To assess the accuracy of the ACS NSQIP calculator for estimating risk after operation for gallbladder cancer and extrahepatic cholangiocarcinoma.\nMethods: Adult patients with gallbladder cancer, distal or hilar cholangiocarcinoma who underwent curative-intent, complete resection January, 2000–December, 2014 were included. The ability of the NSQIP calculator to accurately predict a particular outcome was assessed using the c-statistic (0.7 or above score for reasonable models) and Brier score (zero score for perfect models).\nResults: 854 adult patients were included. The most commonly performed procedures included right or left hepatic lobectomy (254, 29.7%), pancreaticoduodenectomy (132, 15.5%) and trisegmentectomy (118, 13.8%). 185 patients experienced surgical site infection (SSI) (21.7%, median predicted risk of 9.6%, range: 1.9–36.6%). There was 2.1% mortality (median predicted risk of 0.5%, range: 0–19.4%). There were 57 (6.7%) reoperations (median predicted risk of 3.3%, range: 0.9–13.2%). 169 (19.7%) patients were readmitted (median predicted risk of 9.1%, range: 2.6–32.2%). The median length of stay in the cohort was 8 days (Range: 0 119 days) and the median predicted length of stay was 6.5 days (Range: 2.5–25.5 days). The c-statistics for SSI, mortality, reoperation and readmission were 0.64, 0.74, 0.68 and 0.57 and Brier scores were 0.17, 0.02, 0.06 and 0.16 respectively (FIGURE).\nConclusion: The ACS NSQIP Risk Calculator estimates the risk of mortality reasonably well for patients with gallbladder and extrahepatic biliary malignancy but generally underestimates risk of several other postoperative complications. Future modifications of the calculator for some patient populations are needed before widespread use of the tool can be encouraged.","Source":"Google Scholar","category":"HUMAN","training_data":"Evaluating The American College Of Surgeons National Surgical Improvement Project Risk Calculator In Extrahepatic Biliary Malignancy: Results From The Us Extrahepatic Biliary Malignancy Consortium Objective: To assess the accuracy of the ACS NSQIP calculator for estimating risk after operation for gallbladder cancer and extrahepatic cholangiocarcinoma.\nMethods: Adult patients with gallbladder cancer, distal or hilar cholangiocarcinoma who underwent curative-intent, complete resection January, 2000–December, 2014 were included. The ability of the NSQIP calculator to accurately predict a particular outcome was assessed using the c-statistic (0.7 or above score for reasonable models) and Brier score (zero score for perfect models).\nResults: 854 adult patients were included. The most commonly performed procedures included right or left hepatic lobectomy (254, 29.7%), pancreaticoduodenectomy (132, 15.5%) and trisegmentectomy (118, 13.8%). 185 patients experienced surgical site infection (SSI) (21.7%, median predicted risk of 9.6%, range: 1.9–36.6%). There was 2.1% mortality (median predicted risk of 0.5%, range: 0–19.4%). There were 57 (6.7%) reoperations (median predicted risk of 3.3%, range: 0.9–13.2%). 169 (19.7%) patients were readmitted (median predicted risk of 9.1%, range: 2.6–32.2%). The median length of stay in the cohort was 8 days (Range: 0 119 days) and the median predicted length of stay was 6.5 days (Range: 2.5–25.5 days). The c-statistics for SSI, mortality, reoperation and readmission were 0.64, 0.74, 0.68 and 0.57 and Brier scores were 0.17, 0.02, 0.06 and 0.16 respectively (FIGURE).\nConclusion: The ACS NSQIP Risk Calculator estimates the risk of mortality reasonably well for patients with gallbladder and extrahepatic biliary malignancy but generally underestimates risk of several other postoperative complications. Future modifications of the calculator for some patient populations are needed before widespread use of the tool can be encouraged. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"role overexpression traf4 predicting prognosis intrahepatic cholangiocarcinoma incidence intrahepatic cholangiocarcinoma icc progressively increasing worldwide prognosis remains poor accumulating evidence demonstrated tumor necrosis factor receptor associated factor 4 traf4 adaptor protein involved carcinogenesis progression several tumor types however function traf4 predicting prognosis mediating migration invasion icc remains elucidated present study immunohistochemistry western blotting reverse transcription quantitative polymerase chain reaction assays used determine expression traf4 mrna protein levels icc tissues significantly higher compared non tumor tissues overexpression traf4 positively correlated poor differentiation regional lymphatic metastasis high tumor node metastasis staging inhibiting expression traf4 using small interfering rna decreased migration invasion icc cells vitro addition akt inhibitor perifosine eliminated effect traf4 invasion migration icc cells vitro clinically overexpression traf4 correlated shorter overall survival rate elevated recurrence rate patients icc furthermore patients icc high expression traf4 lymphatic metastasis closely associated poorer prognosis compared groups multivariate analysis indicated overexpression traf4 independent prognostic indicator patients icc identified high level traf4 facilitated invasiveness icc cells via activation akt signaling overexpression traf4 may prognostic biomarker candidate therapeutic target patients icc stn","probabilities":0.7777778,"Title":"Role Of The Overexpression Of Traf4 In Predicting The Prognosis Of Intrahepatic Cholangiocarcinoma","Abstract":"The incidence of intrahepatic cholangiocarcinoma (ICC) is progressively increasing worldwide, and its prognosis remains poor. Accumulating evidence has demonstrated that tumor necrosis factor receptor-associated factor 4 (TRAF4), an adaptor protein, is involved in the carcinogenesis and progression of several tumor types. However, the function of TRAF4 in predicting prognosis, and mediating migration and invasion of ICC remains to be elucidated. In the present study, immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine that the expression of TRAF4 at the mRNA and protein levels in ICC tissues was significantly higher compared with that in non‑tumor tissues. The overexpression of TRAF4 was positively correlated with poor differentiation, regional lymphatic metastasis, and high tumor‑node-metastasis staging. Inhibiting the expression of TRAF4 using small interfering RNA decreased the migration and invasion of ICC cells in vitro. In addition, the AKT inhibitor perifosine eliminated the effect of TRAF4 on the invasion and migration of ICC cells in vitro. Clinically, the overexpression of TRAF4 was correlated with shorter overall survival rate and elevated recurrence rate in patients with ICC. Furthermore, patients with ICC with a high expression of TRAF4 and lymphatic metastasis were closely associated with a poorer prognosis compared with the other groups. Multivariate analysis indicated that the overexpression of TRAF4 was an independent prognostic indicator for patients with ICC. It was identified that a high level of TRAF4 facilitated the invasiveness of ICC cells via the activation of AKT signaling. The overexpression of TRAF4 may be a prognostic biomarker and candidate therapeutic target for patients with ICC.","Source":"STN","category":"ANIMAL","training_data":"Role Of The Overexpression Of Traf4 In Predicting The Prognosis Of Intrahepatic Cholangiocarcinoma The incidence of intrahepatic cholangiocarcinoma (ICC) is progressively increasing worldwide, and its prognosis remains poor. Accumulating evidence has demonstrated that tumor necrosis factor receptor-associated factor 4 (TRAF4), an adaptor protein, is involved in the carcinogenesis and progression of several tumor types. However, the function of TRAF4 in predicting prognosis, and mediating migration and invasion of ICC remains to be elucidated. In the present study, immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction assays were used to determine that the expression of TRAF4 at the mRNA and protein levels in ICC tissues was significantly higher compared with that in non‑tumor tissues. The overexpression of TRAF4 was positively correlated with poor differentiation, regional lymphatic metastasis, and high tumor‑node-metastasis staging. Inhibiting the expression of TRAF4 using small interfering RNA decreased the migration and invasion of ICC cells in vitro. In addition, the AKT inhibitor perifosine eliminated the effect of TRAF4 on the invasion and migration of ICC cells in vitro. Clinically, the overexpression of TRAF4 was correlated with shorter overall survival rate and elevated recurrence rate in patients with ICC. Furthermore, patients with ICC with a high expression of TRAF4 and lymphatic metastasis were closely associated with a poorer prognosis compared with the other groups. Multivariate analysis indicated that the overexpression of TRAF4 was an independent prognostic indicator for patients with ICC. It was identified that a high level of TRAF4 facilitated the invasiveness of ICC cells via the activation of AKT signaling. The overexpression of TRAF4 may be a prognostic biomarker and candidate therapeutic target for patients with ICC. STN","prediction_labels":"ANIMAL"},{"cleaned":"hispidulin inhibits proliferation enhances chemosensitivity gallbladder cancer cells targeting hif 1a gallbladder cancer gbc aggressive malignancy bile duct associated low 5 year survival poor prognosis transcription factor hif 1 implicated angiogenesis cell survival epithelial mesenchymal transition emt invasiveness gbc study investigated role hif 1 pathobilogy gbc effect hispidulin molecular events controlled transcription factor observed hispidulin caused induction apoptosis blockade growth cell cycle progression gbc cells results demonstrated first time hispidulin exerted anti tumor effect involved suppression hif 1 signaling hispidulin found repress expression hif 1 protein dose dependently without affecting hif 1 mrna expression addition inhibition hif 1 protein synthesis revealed mediated activation ampk signaling hispidulin also sensitized tumor cells gemcitabine 5 fluoroucil regulating hif 1 p gp signaling given low cost exceedingly safe profile hispidulin appears promising novel chemosensitizer gbc treatment stn","probabilities":0.9467213,"Title":"Hispidulin Inhibits Proliferation And Enhances Chemosensitivity Of Gallbladder Cancer Cells By Targeting Hif-1A","Abstract":"Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investigated the role of HIF-1α in the pathobilogy of GBC and effect of hispidulin on the molecular events controlled by this transcription factor. We observed that hispidulin caused induction of apoptosis, blockade of growth and cell cycle progression in GBC cells. Our results have demonstrated for the first time that hispidulin-exerted anti-tumor effect involved the suppression of HIF-1α signaling. Hispidulin was found to repress the expression of HIF-1α protein dose-dependently without affecting the HIF-1α mRNA expression. In addition, the inhibition of HIF-1α protein synthesis was revealed to be mediated through the activation of AMPK signaling. Hispidulin also sensitized the tumor cells to Gemcitabine and 5-Fluoroucil by down-regulating HIF-1α/P-gp signaling. Given the low cost and exceedingly safe profile, hispidulin appears to be a promising and novel chemosensitizer for GBC treatment.","Source":"STN","category":"ANIMAL","training_data":"Hispidulin Inhibits Proliferation And Enhances Chemosensitivity Of Gallbladder Cancer Cells By Targeting Hif-1A Gallbladder cancer (GBC) is an aggressive malignancy of the bile duct, which is associated with a low (5-year) survival and poor prognosis. The transcription factor HIF-1α is implicated in the angiogenesis, cell survival, epithelial mesenchymal transition (EMT) and invasiveness of GBC. In this study, we have investigated the role of HIF-1α in the pathobilogy of GBC and effect of hispidulin on the molecular events controlled by this transcription factor. We observed that hispidulin caused induction of apoptosis, blockade of growth and cell cycle progression in GBC cells. Our results have demonstrated for the first time that hispidulin-exerted anti-tumor effect involved the suppression of HIF-1α signaling. Hispidulin was found to repress the expression of HIF-1α protein dose-dependently without affecting the HIF-1α mRNA expression. In addition, the inhibition of HIF-1α protein synthesis was revealed to be mediated through the activation of AMPK signaling. Hispidulin also sensitized the tumor cells to Gemcitabine and 5-Fluoroucil by down-regulating HIF-1α/P-gp signaling. Given the low cost and exceedingly safe profile, hispidulin appears to be a promising and novel chemosensitizer for GBC treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"diabetes mellitus increased risk biliary tract cancer systematic review meta analysis objective epidemiological evidences indicate diabetic individuals may increased risk several cancers however relationships diabetes risk cancers biliary tract subsites remain unclear methods provide quantitative assessment relationship identified studies literature search medline 1 january 1966 embase 1 january 1974 31 july 2010 searching reference lists pertinent articles summary relative risks corresponding 95 confidence intervals calculated random effect model results analysis 21 studies 8 case control 13 cohort studies found diabetes associated increased risk biliary tract cancer compared diabetes summary rrs 1 43 95 ci 1 18 1 72 significant heterogeneity among studies p 0 001 positive association also found diabetes risk gallbladder cancer extrahepatic cholangiocarcinoma cancer ampulla vater significant publication bias found conclusion findings strongly support link diabetes increased risk cancer biliary tract subsites gallbladder cancer extrahepatic cholangiocarcinoma cancer ampulla vater pubmed","probabilities":0.9799733,"Title":"Diabetes mellitus and increased risk of biliary tract cancer: systematic review and meta-analysis","Abstract":"OBJECTIVE: Epidemiological evidences indicate that diabetic individuals may have an increased risk of several cancers; however, the relationships between diabetes and risk of cancers of biliary tract or its subsites remain unclear. METHODS: To provide a quantitative assessment of this relationship, we identified studies by a literature search of Medline (from 1 January 1966) and EMBASE (from 1 January 1974), through 31 July 2010, and by searching the reference lists of pertinent articles. Summary relative risks with corresponding 95% confidence intervals were calculated with a random-effect model. RESULTS: Analysis of 21 studies (8 case-control and 13 cohort studies) found that diabetes was associated with an increased risk of biliary tract cancer, compared with no diabetes (summary RRs = 1.43, 95% CI = 1.18-1.72), with significant heterogeneity among studies (p = 0.001). The positive association was also found between diabetes and risk of gallbladder cancer or extrahepatic cholangiocarcinoma, but not cancer of ampulla of Vater. No significant publication bias was found. CONCLUSION: These findings strongly support the link between diabetes and increased risk of cancer of biliary tract and its subsites: gallbladder cancer or extrahepatic cholangiocarcinoma, but not cancer of ampulla of Vater.","Source":"PubMed","category":"HUMAN","training_data":"Diabetes mellitus and increased risk of biliary tract cancer: systematic review and meta-analysis OBJECTIVE: Epidemiological evidences indicate that diabetic individuals may have an increased risk of several cancers; however, the relationships between diabetes and risk of cancers of biliary tract or its subsites remain unclear. METHODS: To provide a quantitative assessment of this relationship, we identified studies by a literature search of Medline (from 1 January 1966) and EMBASE (from 1 January 1974), through 31 July 2010, and by searching the reference lists of pertinent articles. Summary relative risks with corresponding 95% confidence intervals were calculated with a random-effect model. RESULTS: Analysis of 21 studies (8 case-control and 13 cohort studies) found that diabetes was associated with an increased risk of biliary tract cancer, compared with no diabetes (summary RRs = 1.43, 95% CI = 1.18-1.72), with significant heterogeneity among studies (p = 0.001). The positive association was also found between diabetes and risk of gallbladder cancer or extrahepatic cholangiocarcinoma, but not cancer of ampulla of Vater. No significant publication bias was found. CONCLUSION: These findings strongly support the link between diabetes and increased risk of cancer of biliary tract and its subsites: gallbladder cancer or extrahepatic cholangiocarcinoma, but not cancer of ampulla of Vater. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term results outcome predicting factors patients undergoing major hepatic resection klatskin tumor objectives major hepatic resection regarded potenially curative procedure patients bismuth iii type bile duct carcinoma study objective review results 10 year prospective evaluation patients operated curative intent bismuth iii type lesion 1 3 year follow methods study conducted 134 patients bismuth iii type hilar carcinoma treated 2000 2009 94 70 1 suitable surgery underwent major hepatic resection outcome evaluated assessment patient tumor clinicpathologic factors completeness resection survival results major hepatic redections comprised 62 right 32 left hepatectomies r0 r1 r2 resection achieved 40 42 21 22 3 33 35 2 respectively operative mortality rate 9 5 1 3 year survival 69 1 24 5 respectively univariate analysis showed unfavorable tumor biology v2 22 7 p 0 001 incompletness resection v2 43 0 p 0 001 presence post operative complications v2 61 0 p 0 001 associated patient survival multivariate analysis wald test indicated tumor uicc stage incompletness tumor resection presence serious post operative complications outcome prognostic factors w 10 37 p 0 006 w 4 45 p 0 003 w 7 9 p 0 001 respectively conclusion tumor free margin great concern major hepatectomy bismuth iii type hilar carcinoma stage tumor development imperfection surgical procedure hinder gaining desired oncologic extension google scholar","probabilities":0.9799733,"Title":"Long-Term Results And Outcome Predicting Factors In Patients Undergoing Major Hepatic Resection For Klatskin Tumor","Abstract":"Objectives: Major hepatic resection is regarded as the\npotenially curative procedure for patients with Bismuth\nIII type bile duct carcinoma. The study objective was\nto review the results of 10-year prospective evaluation\nof patients that were operated with curative intent for\nBismuth III type lesion at 1- and 3-year follow-up.\nMethods: A study was conducted in 134 patients with\nBismuth III type of hilar carcinoma treated between\n2000 and 2009; 94 (70.1%) were suitable for surgery\nand underwent major hepatic resection. The outcome\nwas evaluated by assessment of patient-tumor clinicpathologic\nfactors, completeness of resection and survival.\nResults: Major hepatic redections comprised 62 right\nand 32 left hepatectomies. The R0, R1, and R2 resection\nwas achieved in 40 (42%), 21 (22.3%) and 33\n(35.2%), respectively. Operative mortality rate was\n9.5%. The 1- and the 3-year survival were 69.1% and\n24.5%, respectively. Univariate analysis showed that\nunfavorable tumor biology (v2 = 22.7, p < 0.001), incompletness\nof resection (v2 = 43.0, p < 0.001) and the\npresence of post-operative complications (v2 = 61.0,\np < 0.001) were associated with patient’s survival. Multivariate\nanalysis (Wald test) indicated tumor UICC\nstage, incompletness in tumor resection and the presence\nof serious post-operative complications as the outcome\nprognostic factors (W = 10.37, p < 0.006,\nW = 4.45, p < 0.003, W = 7.9, p < 0.001, respectively).\nConclusion: A tumor-free margin is of great concern in\nmajor hepatectomy for Bismuth III type of hilar carcinoma.\nThe stage of tumor development and imperfection\nof surgical procedure hinder from gaining the\ndesired oncologic extension.","Source":"Google Scholar","category":"HUMAN","training_data":"Long-Term Results And Outcome Predicting Factors In Patients Undergoing Major Hepatic Resection For Klatskin Tumor Objectives: Major hepatic resection is regarded as the\npotenially curative procedure for patients with Bismuth\nIII type bile duct carcinoma. The study objective was\nto review the results of 10-year prospective evaluation\nof patients that were operated with curative intent for\nBismuth III type lesion at 1- and 3-year follow-up.\nMethods: A study was conducted in 134 patients with\nBismuth III type of hilar carcinoma treated between\n2000 and 2009; 94 (70.1%) were suitable for surgery\nand underwent major hepatic resection. The outcome\nwas evaluated by assessment of patient-tumor clinicpathologic\nfactors, completeness of resection and survival.\nResults: Major hepatic redections comprised 62 right\nand 32 left hepatectomies. The R0, R1, and R2 resection\nwas achieved in 40 (42%), 21 (22.3%) and 33\n(35.2%), respectively. Operative mortality rate was\n9.5%. The 1- and the 3-year survival were 69.1% and\n24.5%, respectively. Univariate analysis showed that\nunfavorable tumor biology (v2 = 22.7, p < 0.001), incompletness\nof resection (v2 = 43.0, p < 0.001) and the\npresence of post-operative complications (v2 = 61.0,\np < 0.001) were associated with patient’s survival. Multivariate\nanalysis (Wald test) indicated tumor UICC\nstage, incompletness in tumor resection and the presence\nof serious post-operative complications as the outcome\nprognostic factors (W = 10.37, p < 0.006,\nW = 4.45, p < 0.003, W = 7.9, p < 0.001, respectively).\nConclusion: A tumor-free margin is of great concern in\nmajor hepatectomy for Bismuth III type of hilar carcinoma.\nThe stage of tumor development and imperfection\nof surgical procedure hinder from gaining the\ndesired oncologic extension. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cholangiographic tumor classification simple patient selection prior hepatopancreatoduodenectomy cholangiocarcinoma background hepatopancreatoduodenectomy hpd employed patients laterally advanced cholangiocarcinoma however survival benefit extended approach remains controversial aim study identify tumor feature benefiting hpd standpoint long term survival patients methods patients cholangiocarcinoma underwent hpd curative intent 2001 2017 retrospectively analyzed tumors radiologically classified preoperative cholangiogram diffuse type defined significant tumor stricture located hilar intrapancreatic duct localized type defined tumor otherwise univariable multivariable analyses performed identify prognostic indicators results 100 study patients 28 28 patients diffuse tumor type remaining 72 72 patients localized tumors former group showed significantly longer lateral length 43 versus 22 mm p 0 001 frequent pancreatic invasion 50 versus 32 p 0 110 advanced classification 64 versus 49 p 0 185 nodal metastasis 57 versus 47 p 0 504 compared latter group survival patients diffuse tumor type significantly worse patients localized tumor type 5 year survival rates 59 0 versus 26 3 respectively p 0 003 multivariable analysis identified four independent factors deteriorating long term survival cholangiographic diffuse tumor p 0 021 higher age p 0 020 percutaneous biliary drainage p 0 007 portal vein resection p 0 007 conclusions presurgical cholangiographic classification diffuse localized type tumor related factor closely associated survival probability therefore may useful feature patient selection prior hpd cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Cholangiographic Tumor Classification for Simple Patient Selection Prior to Hepatopancreatoduodenectomy for Cholangiocarcinoma","Abstract":"BACKGROUND: Hepatopancreatoduodenectomy (HPD) is employed for patients with laterally advanced cholangiocarcinoma. However, the survival benefit of this extended approach remains controversial. The aim of this study is to identify a tumor feature benefiting from HPD from the standpoint of long-term survival. PATIENTS AND METHODS: Patients with cholangiocarcinoma who underwent HPD with curative intent between 2001 and 2017 were retrospectively analyzed. Tumors were radiologically classified by preoperative cholangiogram. Diffuse type was defined as significant tumor/stricture located from the hilar to intrapancreatic duct; localized type was defined as tumor otherwise. Univariable and multivariable analyses were performed to identify prognostic indicators. RESULTS: Of 100 study patients, 28 (28%) patients had diffuse tumor type, while the remaining 72 (72%) patients had localized tumors. The former group showed significantly longer lateral length (43 versus 22 mm, P < 0.001) and more frequent pancreatic invasion (50% versus 32%, P = 0.110), advanced T classification (64% versus 49%, P = 0.185), and nodal metastasis (57% versus 47%, P = 0.504), compared with the latter group. The survival for patients with diffuse tumor type was significantly worse than that for patients with localized tumor type, with 5-year survival rates of 59.0% versus 26.3%, respectively (P = 0.003). Multivariable analysis identified four independent factors deteriorating long-term survival: cholangiographic diffuse tumor (P = 0.021), higher age (P = 0.020), percutaneous biliary drainage (P = 0.007), and portal vein resection (P = 0.007). CONCLUSIONS: Presurgical cholangiographic classification, diffuse or localized type, is a tumor-related factor closely associated with survival probability; therefore, it may be a useful feature for patient selection prior to HPD for cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiographic Tumor Classification for Simple Patient Selection Prior to Hepatopancreatoduodenectomy for Cholangiocarcinoma BACKGROUND: Hepatopancreatoduodenectomy (HPD) is employed for patients with laterally advanced cholangiocarcinoma. However, the survival benefit of this extended approach remains controversial. The aim of this study is to identify a tumor feature benefiting from HPD from the standpoint of long-term survival. PATIENTS AND METHODS: Patients with cholangiocarcinoma who underwent HPD with curative intent between 2001 and 2017 were retrospectively analyzed. Tumors were radiologically classified by preoperative cholangiogram. Diffuse type was defined as significant tumor/stricture located from the hilar to intrapancreatic duct; localized type was defined as tumor otherwise. Univariable and multivariable analyses were performed to identify prognostic indicators. RESULTS: Of 100 study patients, 28 (28%) patients had diffuse tumor type, while the remaining 72 (72%) patients had localized tumors. The former group showed significantly longer lateral length (43 versus 22 mm, P < 0.001) and more frequent pancreatic invasion (50% versus 32%, P = 0.110), advanced T classification (64% versus 49%, P = 0.185), and nodal metastasis (57% versus 47%, P = 0.504), compared with the latter group. The survival for patients with diffuse tumor type was significantly worse than that for patients with localized tumor type, with 5-year survival rates of 59.0% versus 26.3%, respectively (P = 0.003). Multivariable analysis identified four independent factors deteriorating long-term survival: cholangiographic diffuse tumor (P = 0.021), higher age (P = 0.020), percutaneous biliary drainage (P = 0.007), and portal vein resection (P = 0.007). CONCLUSIONS: Presurgical cholangiographic classification, diffuse or localized type, is a tumor-related factor closely associated with survival probability; therefore, it may be a useful feature for patient selection prior to HPD for cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"inhibitor differentiation proteins influence prognosis biliary tract cancer aim investigate expression clinical relevance inhibitor differentiation id proteins biliary tract cancer methods id protein expression analyzed 129 samples patients advanced biliary tract cancer btc 45 extrahepatic 50 intrahepatic 34 gallbladder cancers compared normal controls correlated clinical pathological parameters results id1 3 proteins frequently overexpressed btc subtypes analyzed correlation increased id protein expression tumor grading tumor subtype treatment response detected survival influenced primary tumor localization extrahepatic vs intrahepatic gall bladder cancer os 1 5 years vs 0 9 years vs 0 7 years p 0 002 stage diagnosis os 2 7 years stage vs 0 6 years stage iv p 0 001 resection status response systemic chemotherapy multivariate model id protein expression correlate clinical prognosis nevertheless trend shorter os patients loss cytoplasmic id4 protein expression p 0 076 conclusion id protein expression frequently deregulated btc influence clinical prognosis usefulness prognostic biomarkers btc limited pubmed","probabilities":0.9799733,"Title":"Inhibitor of differentiation proteins do not influence prognosis of biliary tract cancer","Abstract":"AIM: To investigate the expression and clinical relevance of inhibitor of differentiation (ID) proteins in biliary tract cancer. METHODS: ID protein expression was analyzed in 129 samples from patients with advanced biliary tract cancer (BTC) (45 extrahepatic, 50 intrahepatic, and 34 gallbladder cancers), compared to normal controls and correlated with clinical an pathological parameters. RESULTS: ID1-3 proteins are frequently overexpressed in all BTC subtypes analyzed. No correlation between increased ID protein expression and tumor grading, tumor subtype or treatment response was detected. Survival was influenced primary tumor localization (extrahepatic vs intrahepatic and gall bladder cancer, OS 1.5 years vs 0.9 years vs 0.7 years, P = 0.002), by stage at diagnosis (OS 2.7 years in stage I vs 0.6 years in stage IV, P < 0.001), resection status and response to systemic chemotherapy. In a multivariate model, ID protein expression did not correlate with clinical prognosis. Nevertheless, there was a trend of shorter OS in patients with loss of cytoplasmic ID4 protein expression (P = 0.076). CONCLUSION: ID protein expression is frequently deregulated in BTC but does not influence clinical prognosis. Their usefulness as prognostic biomarkers in BTC is very limited.","Source":"PubMed","category":"HUMAN","training_data":"Inhibitor of differentiation proteins do not influence prognosis of biliary tract cancer AIM: To investigate the expression and clinical relevance of inhibitor of differentiation (ID) proteins in biliary tract cancer. METHODS: ID protein expression was analyzed in 129 samples from patients with advanced biliary tract cancer (BTC) (45 extrahepatic, 50 intrahepatic, and 34 gallbladder cancers), compared to normal controls and correlated with clinical an pathological parameters. RESULTS: ID1-3 proteins are frequently overexpressed in all BTC subtypes analyzed. No correlation between increased ID protein expression and tumor grading, tumor subtype or treatment response was detected. Survival was influenced primary tumor localization (extrahepatic vs intrahepatic and gall bladder cancer, OS 1.5 years vs 0.9 years vs 0.7 years, P = 0.002), by stage at diagnosis (OS 2.7 years in stage I vs 0.6 years in stage IV, P < 0.001), resection status and response to systemic chemotherapy. In a multivariate model, ID protein expression did not correlate with clinical prognosis. Nevertheless, there was a trend of shorter OS in patients with loss of cytoplasmic ID4 protein expression (P = 0.076). CONCLUSION: ID protein expression is frequently deregulated in BTC but does not influence clinical prognosis. Their usefulness as prognostic biomarkers in BTC is very limited. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ca9 overexpression independent favorable prognostic marker intrahepatic cholangiocarcinoma aim study evaluate expression carbonic anhydrase ix ca9 identify prognostic significance intrahepatic cholangiocarcinoma ihcc performed immunohistochemistry ihc ca9 total 85 ihccs ca9 overexpression observed 38 85 44 7 ihccs ca9 overexpression related tumors intraductal growth mass forming periductal infiltrative type ca9 overexpression observed tumors well moderate differentiation poor differentiation without lymph node metastasis significant correlation observed ca9 overexpression tumor size pt stage lymphovascular invasion intrahepatic cholangiocarcinomas ca9 overexpression showed better overall survival without expression p 0 001 multivariate analysis lymph node metastasis 95 ci 2 103 1 167 3 791 p 0 013 independent poor prognostic factor ihcc ca9 overexpression showed 0 5 fold 95 confidence interval 0 328 0 944 lower risk death compared weak expression ca9 overexpression related histologic differentiation independent good prognostic factor stn","probabilities":0.9799733,"Title":"Ca9 Overexpression Is An Independent Favorable Prognostic Marker In Intrahepatic Cholangiocarcinoma","Abstract":"The aim of this study is to evaluate the expression of carbonic anhydrase IX (CA9) and to identify its prognostic significance in intrahepatic cholangiocarcinoma (IHCC). We performed immunohistochemistry (IHC) for CA9 in a total of 85 IHCCs. CA9 overexpression was observed in 38 of 85 (44.7%) IHCCs. CA9 overexpression was related to tumors with intraductal growth than mass forming or periductal infiltrative type. CA9 overexpression was more observed in tumors with well/moderate differentiation than poor differentiation and without lymph node metastasis. No significant correlation was observed in CA9 overexpression with tumor size, pT, stage and lymphovascular invasion. Intrahepatic cholangiocarcinomas with CA9 overexpression showed better overall survival than that without expression (P = 0.001). In multivariate analysis, lymph node metastasis (95% CI: 2.103 (1.167-3.791), P = 0.013) was an independent poor prognostic factor. IHCC with CA9 overexpression showed a 0.5-fold (95% confidence interval, 0.328-0.944) lower risk of death compared with those of no or weak expression. CA9 overexpression was related to histologic differentiation and an independent good prognostic factor.","Source":"STN","category":"HUMAN","training_data":"Ca9 Overexpression Is An Independent Favorable Prognostic Marker In Intrahepatic Cholangiocarcinoma The aim of this study is to evaluate the expression of carbonic anhydrase IX (CA9) and to identify its prognostic significance in intrahepatic cholangiocarcinoma (IHCC). We performed immunohistochemistry (IHC) for CA9 in a total of 85 IHCCs. CA9 overexpression was observed in 38 of 85 (44.7%) IHCCs. CA9 overexpression was related to tumors with intraductal growth than mass forming or periductal infiltrative type. CA9 overexpression was more observed in tumors with well/moderate differentiation than poor differentiation and without lymph node metastasis. No significant correlation was observed in CA9 overexpression with tumor size, pT, stage and lymphovascular invasion. Intrahepatic cholangiocarcinomas with CA9 overexpression showed better overall survival than that without expression (P = 0.001). In multivariate analysis, lymph node metastasis (95% CI: 2.103 (1.167-3.791), P = 0.013) was an independent poor prognostic factor. IHCC with CA9 overexpression showed a 0.5-fold (95% confidence interval, 0.328-0.944) lower risk of death compared with those of no or weak expression. CA9 overexpression was related to histologic differentiation and an independent good prognostic factor. STN","prediction_labels":"HUMAN"},{"cleaned":"effect inflammatory markers survival advanced biliary tract carcinoma treated gemcitabine oxaliplatin regimen background advanced biliary tract carcinoma btc prognosis poor overall survival less 1 year study aimed determine effect neutrophil lymphocyte ratio nlr derived neutrophil lymphocyte ratio dnlr c reactive protein crp albumin ratio car prognostic nutritional index pni survival btc patients treated gemcitabine oxaliplatin gemox regimen methods data 53 patients advanced btc evaluated retrospectively association inflammatory markers 6 month pfs 12 month os compared log rank test optimal cutoff values determined receiver operating characteristic roc curve analysis nlr dnlr car pni grouped based cutoff points 1 95 1 15 0 57 33 respectively univariate multivariate analyses used assess prognostic values survival results lower dnlr 1 15 prognostic higher 6 month pfs 12 month os rates lower nlr 1 95 prognostic higher 6 month pfs rates car pni statistically significant effects survival conclusions pretreatment dnlr nlr values advanced btc used predictive markers survival patients undergoing gemox regimen stn","probabilities":0.9799733,"Title":"The Effect Of Inflammatory Markers On Survival In Advanced Biliary Tract Carcinoma Treated With Gemcitabine/Oxaliplatin Regimen","Abstract":"Background: In advanced biliary tract carcinoma (BTC), the prognosis is very poor, and the overall survival is less than 1 year. This study aimed to determine the effect of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), C-reactive protein (CRP)/albumin ratio (CAR), and prognostic nutritional index (PNI) on the survival of BTC patients treated with gemcitabine/oxaliplatin (GEMOX) regimen. \r\n\r\n Methods: Data of 53 patients with advanced BTC were evaluated retrospectively. Association between inflammatory markers and 6-month PFS and 12-month OS were compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. NLR, dNLR, CAR, and PNI were grouped based on cutoff points 1.95, 1.15, 0.57, and 33, respectively. Univariate and multivariate analyses were used to assess their prognostic values for survival. \r\n\r\n Results: Lower dNLR (< 1.15) was prognostic for higher 6-month PFS and 12-month OS rates, while lower NLR (< 1.95) was prognostic for higher 6-month PFS rates only. CAR and PNI did not have statistically significant effects on survival. \r\n\r\n Conclusions: Pretreatment dNLR and NLR values in advanced BTC can be used as predictive markers for survival in patients undergoing the GEMOX regimen.","Source":"STN","category":"HUMAN","training_data":"The Effect Of Inflammatory Markers On Survival In Advanced Biliary Tract Carcinoma Treated With Gemcitabine/Oxaliplatin Regimen Background: In advanced biliary tract carcinoma (BTC), the prognosis is very poor, and the overall survival is less than 1 year. This study aimed to determine the effect of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), C-reactive protein (CRP)/albumin ratio (CAR), and prognostic nutritional index (PNI) on the survival of BTC patients treated with gemcitabine/oxaliplatin (GEMOX) regimen. \r\n\r\n Methods: Data of 53 patients with advanced BTC were evaluated retrospectively. Association between inflammatory markers and 6-month PFS and 12-month OS were compared by the log-rank test. The optimal cutoff values were determined by a receiver operating characteristic (ROC) curve analysis. NLR, dNLR, CAR, and PNI were grouped based on cutoff points 1.95, 1.15, 0.57, and 33, respectively. Univariate and multivariate analyses were used to assess their prognostic values for survival. \r\n\r\n Results: Lower dNLR (< 1.15) was prognostic for higher 6-month PFS and 12-month OS rates, while lower NLR (< 1.95) was prognostic for higher 6-month PFS rates only. CAR and PNI did not have statistically significant effects on survival. \r\n\r\n Conclusions: Pretreatment dNLR and NLR values in advanced BTC can be used as predictive markers for survival in patients undergoing the GEMOX regimen. STN","prediction_labels":"HUMAN"},{"cleaned":"alcam novel cytoplasmic membrane protein tnf stimulated invasive cholangiocarcinoma cells background cholangiocarcinoma cca bile duct cancer incurable high mortality rate due lack effective early diagnosis treatment identifying cytoplasmic membrane proteins invasive cca facilitate cancer progression contribute toward development novel tumor markers effective chemotherapy materials methods invasive cca cell line kku 100 stimulated using tnf biotinylated purified mass spectrometry analysis novel proteins expressed selected mrnas expression levels determined real time rt pcr addition expression alcam selected observation western blot analysis immunofluorescent imaging antibody neutralization assay results comparing proteomics profile tnf induced invasive non treated control cells expression seven novel proteins observed cytoplasmic membrane tnf stimulated cca cells among alcam novel candidate showed significant higher mrna protein levels immunofluorescent assay also supported alcam expressed cell membrane cancer increasing intensity associated tnf conclusions study indicated alcam may novel protein candidate expressed cytoplasmic membranes invasive cca cells used biomarker development diagnosis prognosis drug antibody based targeted therapies future stn","probabilities":0.9467213,"Title":"Alcam Is A Novel Cytoplasmic Membrane Protein In Tnf-A Stimulated Invasive Cholangiocarcinoma Cells","Abstract":"Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. \r\n\r\n Materials and methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-α and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. \r\n\r\n Results: After comparing the proteomics profile of TNF-α induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-α stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA- and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-α. \r\n\r\nConclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future.","Source":"STN","category":"ANIMAL","training_data":"Alcam Is A Novel Cytoplasmic Membrane Protein In Tnf-A Stimulated Invasive Cholangiocarcinoma Cells Background: Cholangiocarcinoma (CCA), or bile duct cancer, is incurable with a high mortality rate due to a lack of effective early diagnosis and treatment. Identifying cytoplasmic membrane proteins of invasive CCA that facilitate cancer progression would contribute toward the development of novel tumor markers and effective chemotherapy. \r\n\r\n Materials and methods: An invasive CCA cell line (KKU-100) was stimulated using TNF-α and then biotinylated and purified for mass spectrometry analysis. Novel proteins expressed were selected and their mRNAs expression levels were determined by real-time RT-PCR. In addition, the expression of ALCAM was selected for further observation by Western blot analysis, immunofluorescent imaging, and antibody neutralization assay. \r\n\r\n Results: After comparing the proteomics profile of TNF-α induced invasive with non-treated control cells, over-expression of seven novel proteins was observed in the cytoplasmic membrane of TNF-α stimulated CCA cells. Among these, ALCAM is a novel candidate which showed significant higher mRNA- and protein levels. Immunofluorescent assay also supported that ALCAM was expressed on the cell membrane of the cancer, with increasing intensity associated with TNF-α. \r\n\r\nConclusions: This study indicated that ALCAM may be a novel protein candidate expressed on cytoplasmic membranes of invasive CCA cells that could be used as a biomarker for development of diagnosis, prognosis, and drug or antibody-based targeted therapies in the future. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic significance risk prediction model lymph node metastasis resectable intrahepatic cholangiocarcinoma require lymph node dissection background lymph node ln metastasis portends worse prognosis following resection intrahepatic cholangiocarcinoma icc however lymphadenectomy routinely performed role remains controversial herein developed risk model ln metastasis identifying predictive factors assessed subset patients might benefit ln dissection lnd methods 210 patients underwent curative intent surgery icc retrospectively reviewed preoperative risk model ln metastasis developed following identification preoperative predictive factors using recursive partitioning method results multivariable analysis ca 19 9 level 120 u ml enlarged ln computed tomography tumor location abutting glissonean pedicles independent predictors ln metastasis preoperative risk model classified patients according risk high intermediate low risks rate ln metastasis final pathology 60 9 35 2 3 respectively subgroup analysis among low risk patients performance lnd survival advantage non performance lnd conclusion routine lnd preoperatively diagnosed icc recommended patients intermediate high risk developing ln metastasis may omitted low risk patients stn","probabilities":0.9799733,"Title":"Prognostic Significance Of And Risk Prediction Model For Lymph Node Metastasis In Resectable Intrahepatic Cholangiocarcinoma: Do All Require Lymph Node Dissection?","Abstract":"Background: Lymph node (LN) metastasis portends a worse prognosis following resection of intrahepatic cholangiocarcinoma (ICC); however, lymphadenectomy is not routinely performed, as its role remains controversial. Herein, we developed a risk model for LN metastasis by identifying its predictive factors and assessed a subset of patients who might not benefit from LN dissection (LND). \r\n\r\n Methods: 210 patients who underwent curative-intent surgery for ICC were retrospectively reviewed. A preoperative risk model for LN metastasis was developed following identification of its preoperative predictive factors using the recursive partitioning method. \r\n\r\n Results: In the multivariable analysis, CA 19-9 level of >120 U/mL, an enlarged LN on computed tomography, and a tumor location abutting the Glissonean pedicles were independent predictors of LN metastasis. The preoperative risk model classified the patients according to their risk: high, intermediate, and low risks at a rate of LN metastasis on final pathology of 60.9%, 35%, and 2.3%, respectively. In the subgroup analysis among the low-risk patients, performance of LND had no survival advantage over non-performance of LND. \r\n\r\n Conclusion: Routine LND for preoperatively diagnosed ICC should be recommended to patients at an intermediate and a high risk of developing LN metastasis but may be omitted for low-risk patients.","Source":"STN","category":"HUMAN","training_data":"Prognostic Significance Of And Risk Prediction Model For Lymph Node Metastasis In Resectable Intrahepatic Cholangiocarcinoma: Do All Require Lymph Node Dissection? Background: Lymph node (LN) metastasis portends a worse prognosis following resection of intrahepatic cholangiocarcinoma (ICC); however, lymphadenectomy is not routinely performed, as its role remains controversial. Herein, we developed a risk model for LN metastasis by identifying its predictive factors and assessed a subset of patients who might not benefit from LN dissection (LND). \r\n\r\n Methods: 210 patients who underwent curative-intent surgery for ICC were retrospectively reviewed. A preoperative risk model for LN metastasis was developed following identification of its preoperative predictive factors using the recursive partitioning method. \r\n\r\n Results: In the multivariable analysis, CA 19-9 level of >120 U/mL, an enlarged LN on computed tomography, and a tumor location abutting the Glissonean pedicles were independent predictors of LN metastasis. The preoperative risk model classified the patients according to their risk: high, intermediate, and low risks at a rate of LN metastasis on final pathology of 60.9%, 35%, and 2.3%, respectively. In the subgroup analysis among the low-risk patients, performance of LND had no survival advantage over non-performance of LND. \r\n\r\n Conclusion: Routine LND for preoperatively diagnosed ICC should be recommended to patients at an intermediate and a high risk of developing LN metastasis but may be omitted for low-risk patients. STN","prediction_labels":"HUMAN"},{"cleaned":"validation revised american joint committee cancer staging gallbladder cancer based single institution experience gallbladder cancer rare malignancy often goes undiagnosed advanced stages disease associated poor prognosis potentially curative treatment surgical resection retrospective study aims investigate validity revised 7th edition american joint committee cancer staging criteria determine prognostic factors forty two patients confirmed gallbladder cancer underwent attempted curative resection 1999 2012 university california irvine medical center reviewed survival probability determined using kaplan meier method ten patients underwent laparoscopy deemed unresectable surgical intervention performed r0 surgical resection included radical portal lymphadenectomy liver segment ivb v resection without bile duct resection performed remaining 32 patients n2 nodes resected positive frozen section overall survival probability stage ii patients 100 per cent overall survival probability stage iii patients 80 per cent 95 confidence interval ci 61 99 39 3 per cent 95 ci 28 78 stage iv patients study demonstrates 7th edition clinical stage stage liver involvement statistically significant predictors prognosis data also demonstrate benefit extended resection patients even stage iii iv disease pubmed","probabilities":0.9799733,"Title":"Validation of revised American Joint Committee on Cancer staging for gallbladder cancer based on a single institution experience","Abstract":"Gallbladder cancer is a rare malignancy, which often goes undiagnosed until advanced stages of disease and is associated with poor prognosis. The only potentially curative treatment is surgical resection. This retrospective study aims to investigate the validity of the revised 7th edition American Joint Committee on Cancer staging criteria and determine prognostic factors. Forty-two patients with confirmed gallbladder cancer who underwent attempted curative resection from 1999 to 2012 at the University of California, Irvine Medical Center were reviewed. Survival probability was determined using the Kaplan-Meier method. Ten patients underwent laparoscopy, were deemed unresectable, and no further surgical intervention was performed. R0 surgical resection, which included radical portal lymphadenectomy, liver segment IVb/V resection, with or without bile duct resection, was performed in the remaining 32 patients. N2 nodes were resected if positive on frozen section. Overall survival probability for Stage I to II patients was 100 per cent. Overall survival probability for Stage III patients was 80 per cent (95% confidence interval [CI], 61 to 99%) and 39.3 per cent (95% CI, 28 to 78%) for Stage IV patients. This study demonstrates that 7th edition clinical stage, T stage, and liver involvement are statistically significant predictors of prognosis. These data also demonstrate a benefit to extended resection in patients even with Stage III and IV disease.","Source":"PubMed","category":"HUMAN","training_data":"Validation of revised American Joint Committee on Cancer staging for gallbladder cancer based on a single institution experience Gallbladder cancer is a rare malignancy, which often goes undiagnosed until advanced stages of disease and is associated with poor prognosis. The only potentially curative treatment is surgical resection. This retrospective study aims to investigate the validity of the revised 7th edition American Joint Committee on Cancer staging criteria and determine prognostic factors. Forty-two patients with confirmed gallbladder cancer who underwent attempted curative resection from 1999 to 2012 at the University of California, Irvine Medical Center were reviewed. Survival probability was determined using the Kaplan-Meier method. Ten patients underwent laparoscopy, were deemed unresectable, and no further surgical intervention was performed. R0 surgical resection, which included radical portal lymphadenectomy, liver segment IVb/V resection, with or without bile duct resection, was performed in the remaining 32 patients. N2 nodes were resected if positive on frozen section. Overall survival probability for Stage I to II patients was 100 per cent. Overall survival probability for Stage III patients was 80 per cent (95% confidence interval [CI], 61 to 99%) and 39.3 per cent (95% CI, 28 to 78%) for Stage IV patients. This study demonstrates that 7th edition clinical stage, T stage, and liver involvement are statistically significant predictors of prognosis. These data also demonstrate a benefit to extended resection in patients even with Stage III and IV disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"subgroups lymph node metastasis including extra capsular lymph node involvement survival impact patients extrahepatic bile duct cancer background lymph node metastasis one important prognostic factors extra hepatic bile duct carcinoma exhbdc extra capsular lymph node involvement exclni extension cancer cells nodal capsule perinodal fatty tissue prognostic impact exclni shown significant mainly head neck malignancies recently prognostic impacts exclni evaluated gastrointestinal malignancies however data available regarding incidence prognostic significance extra capsular lymph node involvement exclni resectable exhbdcs aim present study first evaluate incidence exclni surgically treated exhbdcs second determine prognostic impact exclni patients surgically treated exhbdcs methods total 228 patients 110 cases hilar cholangiocarcinoma 118 cases distal cholangiocarcinoma surgically treated exhbdcs included retrospective study exclni defined extension cancer cells nodal capsule perinodal fatty tissue existence exclni prognostic value analyzed subgroup lymph node metastasis results exclni detected 22 patients lymph node metastasis surgically treated exhbdc presence exclni correlated distal cholangiocarcinoma p 0 002 univariate analysis survival perineural invasion vascular invasion histological grade lymph node metastasis statistically significant factors multivariate analysis lymph node metastasis identified significant independent prognostic factor patients resectable exhbdc subgroups lymph node metastasis including presence exclni location lymph node metastasis number lymph node metastasis statistically significant impact survival conclusion exclni present 22 lnm 7 overall patients patients surgical treated exhbdcs exclni impact survival patients surgically treated exhbdcs stn","probabilities":0.7966102,"Title":"Subgroups Of Lymph Node Metastasis Including Extra Capsular Lymph Node Involvement Had No Survival Impact In Patients With Extrahepatic Bile Duct Cancer","Abstract":"Background: Lymph node metastasis is one of the most important prognostic factors for extra-hepatic bile duct carcinoma (ExHBDC). Extra capsular lymph node involvement (ExCLNI) is the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The prognostic impact of ExCLNI has been shown to be significant mainly in head and neck malignancies. Recently, the prognostic impacts of ExCLNI have evaluated in gastrointestinal malignancies. However no data is available regarding the incidence and prognostic significance of extra-capsular lymph node involvement (ExCLNI) in resectable ExHBDCs. The aim of the present study is first to evaluate the incidence of ExCLNI in surgically-treated ExHBDCs and second, to determine the prognostic impact of ExCLNI in patients with surgically-treated ExHBDCs. \n\n Methods: A total of 228 patients (110 cases of hilar cholangiocarcinoma and 118 cases of distal cholangiocarcinoma) with surgically-treated ExHBDCs were included in this retrospective study. ExCLNI was defined as the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The existence of ExCLNI and its prognostic value were analyzed as a subgroup of lymph node metastasis. \n\n Results: ExCLNI was detected in only 22% of patients with lymph node metastasis of surgically-treated ExHBDC. The presence of ExCLNI correlated with distal cholangiocarcinoma (p = 0.002). On univariate analysis for survival, perineural invasion, vascular invasion, histological grade, and lymph node metastasis were statistically significant factors. On multivariate analysis, only lymph node metastasis was identified as a significant independent prognostic factor in patients with resectable ExHBDC. Subgroups of lymph node metastasis including the presence of ExCLNI, location of lymph node metastasis, and the number of lymph node metastasis had no statistically significant impact on survival. \n\n Conclusion: ExCLNI was present in only 22% of the LNM (7% of overall patients) in patients with surgical treated ExHBDCs. And ExCLNI would have no impact on the survival of patients with surgically-treated ExHBDCs.","Source":"STN","category":"HUMAN","training_data":"Subgroups Of Lymph Node Metastasis Including Extra Capsular Lymph Node Involvement Had No Survival Impact In Patients With Extrahepatic Bile Duct Cancer Background: Lymph node metastasis is one of the most important prognostic factors for extra-hepatic bile duct carcinoma (ExHBDC). Extra capsular lymph node involvement (ExCLNI) is the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The prognostic impact of ExCLNI has been shown to be significant mainly in head and neck malignancies. Recently, the prognostic impacts of ExCLNI have evaluated in gastrointestinal malignancies. However no data is available regarding the incidence and prognostic significance of extra-capsular lymph node involvement (ExCLNI) in resectable ExHBDCs. The aim of the present study is first to evaluate the incidence of ExCLNI in surgically-treated ExHBDCs and second, to determine the prognostic impact of ExCLNI in patients with surgically-treated ExHBDCs. \n\n Methods: A total of 228 patients (110 cases of hilar cholangiocarcinoma and 118 cases of distal cholangiocarcinoma) with surgically-treated ExHBDCs were included in this retrospective study. ExCLNI was defined as the extension of cancer cells through the nodal capsule into the perinodal fatty tissue. The existence of ExCLNI and its prognostic value were analyzed as a subgroup of lymph node metastasis. \n\n Results: ExCLNI was detected in only 22% of patients with lymph node metastasis of surgically-treated ExHBDC. The presence of ExCLNI correlated with distal cholangiocarcinoma (p = 0.002). On univariate analysis for survival, perineural invasion, vascular invasion, histological grade, and lymph node metastasis were statistically significant factors. On multivariate analysis, only lymph node metastasis was identified as a significant independent prognostic factor in patients with resectable ExHBDC. Subgroups of lymph node metastasis including the presence of ExCLNI, location of lymph node metastasis, and the number of lymph node metastasis had no statistically significant impact on survival. \n\n Conclusion: ExCLNI was present in only 22% of the LNM (7% of overall patients) in patients with surgical treated ExHBDCs. And ExCLNI would have no impact on the survival of patients with surgically-treated ExHBDCs. STN","prediction_labels":"HUMAN"},{"cleaned":"aspirin use risk cholangiocarcinoma whether aspirin use protective cholangiocarcinoma cca remains unclear determined association aspirin use risk factors cca subtype individually hospital based case control study 2395 cca cases 1169 intrahepatic 995 perihilar 231 distal seen mayo clinic rochester mn 2000 2014 enrolled controls selected mayo clinic biobank matched two one cases age sex race residence n 4769 associations aspirin use risk factors cca risk determined aspirin used 591 24 7 cca cases 2129 44 6 controls significant inverse association aspirin use cca subtypes adjusted odds ratios aors 0 35 95 confidence interval ci 0 29 0 42 0 34 95 ci 0 27 0 42 0 29 95 ci 0 19 0 44 intrahepatic perihilar distal cca respectively p 0 001 primary sclerosing cholangitis strongly associated perihilar aor 453 95 ci 104 999 intrahepatic aor 93 4 95 ci 27 1 322 distal aor 34 0 95 ci 3 6 323 cca whereas diabetes associated distal aor 4 2 95 ci 2 5 7 0 perihilar aor 2 9 95 ci 2 2 3 8 intrahepatic aor 2 5 95 ci 2 0 3 2 cca cirrhosis related primary sclerosing cholangitis associated intrahepatic perihilar cca similar aors 14 isolated inflammatory bowel disease without primary sclerosing cholangitis associated cca subtype conclusions aspirin use significantly associated 2 7 fold 3 6 fold decreased risk three cca subtypes study demonstrates individual risk factors confer risk different cca subtypes different extents hepatology 2016 64 785 796 pubmed","probabilities":0.9799733,"Title":"Aspirin use and the risk of cholangiocarcinoma","Abstract":"Whether aspirin use is protective against cholangiocarcinoma (CCA) remains unclear. We determined the association between aspirin use and other risk factors for each CCA subtype individually. In a hospital-based case-control study, 2395 CCA cases (1169 intrahepatic, 995 perihilar, and 231 distal) seen at the Mayo Clinic, Rochester, MN, from 2000 through 2014 were enrolled. Controls selected from the Mayo Clinic Biobank were matched two to one with cases by age, sex, race, and residence (n = 4769). Associations between aspirin use, other risk factors, and CCA risk were determined. Aspirin was used by 591 (24.7%) CCA cases and 2129 (44.6%) controls. There was a significant inverse association of aspirin use with all CCA subtypes, with adjusted odds ratios (AORs) of 0.35 (95% confidence interval [CI], 0.29-0.42), 0.34 (95% CI 0.27-0.42), and 0.29 (95% CI 0.19-0.44) for intrahepatic, perihilar, and distal CCA, respectively (P < 0.001 for all). Primary sclerosing cholangitis was more strongly associated with perihilar (AOR = 453, 95% CI 104-999) than intrahepatic (AOR = 93.4, 95% CI 27.1-322) or distal (AOR = 34.0, 95% CI 3.6-323) CCA, whereas diabetes was more associated with distal (AOR = 4.2, 95% CI 2.5-7.0) than perihilar (AOR = 2.9, 95% CI 2.2-3.8) or intrahepatic (AOR = 2.5, 95% CI 2.0-3.2) CCA. Cirrhosis not related to primary sclerosing cholangitis was associated with both intrahepatic and perihilar CCA, with similar AORs of 14. Isolated inflammatory bowel disease without primary sclerosing cholangitis was not associated with any CCA subtype. CONCLUSIONS: Aspirin use was significantly associated with a 2.7-fold to 3.6-fold decreased risk for the three CCA subtypes; our study demonstrates that individual risk factors confer risk of different CCA subtypes to different extents. (Hepatology 2016;64:785-796).","Source":"PubMed","category":"HUMAN","training_data":"Aspirin use and the risk of cholangiocarcinoma Whether aspirin use is protective against cholangiocarcinoma (CCA) remains unclear. We determined the association between aspirin use and other risk factors for each CCA subtype individually. In a hospital-based case-control study, 2395 CCA cases (1169 intrahepatic, 995 perihilar, and 231 distal) seen at the Mayo Clinic, Rochester, MN, from 2000 through 2014 were enrolled. Controls selected from the Mayo Clinic Biobank were matched two to one with cases by age, sex, race, and residence (n = 4769). Associations between aspirin use, other risk factors, and CCA risk were determined. Aspirin was used by 591 (24.7%) CCA cases and 2129 (44.6%) controls. There was a significant inverse association of aspirin use with all CCA subtypes, with adjusted odds ratios (AORs) of 0.35 (95% confidence interval [CI], 0.29-0.42), 0.34 (95% CI 0.27-0.42), and 0.29 (95% CI 0.19-0.44) for intrahepatic, perihilar, and distal CCA, respectively (P < 0.001 for all). Primary sclerosing cholangitis was more strongly associated with perihilar (AOR = 453, 95% CI 104-999) than intrahepatic (AOR = 93.4, 95% CI 27.1-322) or distal (AOR = 34.0, 95% CI 3.6-323) CCA, whereas diabetes was more associated with distal (AOR = 4.2, 95% CI 2.5-7.0) than perihilar (AOR = 2.9, 95% CI 2.2-3.8) or intrahepatic (AOR = 2.5, 95% CI 2.0-3.2) CCA. Cirrhosis not related to primary sclerosing cholangitis was associated with both intrahepatic and perihilar CCA, with similar AORs of 14. Isolated inflammatory bowel disease without primary sclerosing cholangitis was not associated with any CCA subtype. CONCLUSIONS: Aspirin use was significantly associated with a 2.7-fold to 3.6-fold decreased risk for the three CCA subtypes; our study demonstrates that individual risk factors confer risk of different CCA subtypes to different extents. (Hepatology 2016;64:785-796). PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatic arterial infusion gemcitabine plus oxaliplatin second line treatment locally advanced intrahepatic cholangiocarcinoma preliminary experience background aim study evaluate efficacy tolerability hepatic arterial infusion hai gemcitabine plus oxaliplatin second line treatment unresectable locally advanced intrahepatic cholangiocarcinoma patients methods retrospectively analyzed outcome 12 consecutive patients unresectable locally advanced intrahepatic cholangiocarcinoma treated hai gemcitabine 1 000 mg m 2 30 min followed oxaliplatin 100 mg m 2 2 h repeated every 2 weeks results patients presented disease limited liver failed least one line chemotherapy gemcitabine oxaliplatin best tumor responses using recist criteria partial responses 8 patients stable disease 3 patients least 3 months 1 patient disease progressed resulting disease control rate 91 95 ci 45 100 median overall survival time progression 9 1 months 95 ci 4 9 8 1 20 3 months 95 ci 13 2 49 7 respectively partial responses enabled r0 liver surgery 2 patients stereotactic radiation therapy 3 patients grade 3 4 toxicities included neutropenia 2 patients thrombocytopenia 2 patients oxaliplatin allergy 2 patients conclusions hai combining gemcitabine oxaliplatin showed promising efficacy safety second line treatment locally advanced intrahepatic cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Hepatic arterial infusion of gemcitabine plus oxaliplatin as second-line treatment for locally advanced intrahepatic cholangiocarcinoma: preliminary experience","Abstract":"BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of hepatic arterial infusion (HAI) of gemcitabine plus oxaliplatin as second-line treatment for unresectable locally advanced intrahepatic cholangiocarcinoma. PATIENTS AND METHODS: We retrospectively analyzed the outcome of 12 consecutive patients with unresectable locally advanced intrahepatic cholangiocarcinoma treated with HAI of gemcitabine (1,000 mg/m(2) over 30 min) followed by oxaliplatin (100 mg/m(2) over 2 h), which was repeated every 2 weeks. RESULTS: All patients presented with disease limited to the liver and all had failed at least one line of chemotherapy with gemcitabine and oxaliplatin. The best tumor responses using RECIST criteria were partial responses in 8 patients and stable disease in 3 patients for at least 3 months; in 1 patient, disease progressed, resulting in a disease control rate of 91% (95% CI 45-100%). The median overall survival and time to progression were 9.1 months (95% CI 4.9-8.1) and 20.3 months (95% CI 13.2-49.7), respectively. Partial responses enabled R0 liver surgery in 2 patients and stereotactic radiation therapy in 3 patients. Grade 3/4 toxicities included neutropenia in 2 patients, thrombocytopenia in 2 patients, and oxaliplatin allergy in 2 patients. CONCLUSIONS: HAI combining gemcitabine and oxaliplatin showed promising efficacy and safety as second-line treatment for locally advanced intrahepatic cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Hepatic arterial infusion of gemcitabine plus oxaliplatin as second-line treatment for locally advanced intrahepatic cholangiocarcinoma: preliminary experience BACKGROUND: The aim of this study was to evaluate the efficacy and tolerability of hepatic arterial infusion (HAI) of gemcitabine plus oxaliplatin as second-line treatment for unresectable locally advanced intrahepatic cholangiocarcinoma. PATIENTS AND METHODS: We retrospectively analyzed the outcome of 12 consecutive patients with unresectable locally advanced intrahepatic cholangiocarcinoma treated with HAI of gemcitabine (1,000 mg/m(2) over 30 min) followed by oxaliplatin (100 mg/m(2) over 2 h), which was repeated every 2 weeks. RESULTS: All patients presented with disease limited to the liver and all had failed at least one line of chemotherapy with gemcitabine and oxaliplatin. The best tumor responses using RECIST criteria were partial responses in 8 patients and stable disease in 3 patients for at least 3 months; in 1 patient, disease progressed, resulting in a disease control rate of 91% (95% CI 45-100%). The median overall survival and time to progression were 9.1 months (95% CI 4.9-8.1) and 20.3 months (95% CI 13.2-49.7), respectively. Partial responses enabled R0 liver surgery in 2 patients and stereotactic radiation therapy in 3 patients. Grade 3/4 toxicities included neutropenia in 2 patients, thrombocytopenia in 2 patients, and oxaliplatin allergy in 2 patients. CONCLUSIONS: HAI combining gemcitabine and oxaliplatin showed promising efficacy and safety as second-line treatment for locally advanced intrahepatic cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological significance sox4 expression primary gallbladder carcinoma aim sox4 member sry related hmg box sox transcription factor family demonstrated involved tumorigenesis many human malignancies however role primary gallbladder carcinoma pgc still largely unknown aim study investigate sox4 expression pgc prognostic significance methods 1997 2006 136 patients underwent resection pgc median follow 12 8 months immunostainings sox4 performed archival tissues correlation sox4 expression clinicopathological features including survival analyzed results sox4 expressed 75 0 102 136 pgc normal epithelium gallbladder addition expression sox4 significantly associated low histologic grade p 0 02 low pathologic stage p 0 02 early clinical stage p 0 03 levels sox4 immunostainings pgc tissues positive nodal metastasis also significantly lower without p 0 01 moreover kaplan meier curves showed sox4 expression significantly related better overall p 0 008 disease free survival p 0 01 furthermore multivariate analyses showed sox4 expression independent risk factor overall p 0 03 hazard ratio 3 682 disease free survival p 0 04 hazard ratio 2 215 conclusion data indicate first time expression sox4 pgc significantly correlated favorable clinicopathologic features independent prognostic factor better overall disease free survival patients therefore sox4 might auxiliary parameter predicting malignant behavior pgc virtual slides virtual slide article found http www diagnosticpathology diagnomx eu vs 1534825818694957 pubmed","probabilities":0.75,"Title":"Clinicopathological significance of SOX4 expression in primary gallbladder carcinoma","Abstract":"AIM: SOX4, as a member of the SRY-related HMG-box (SOX) transcription factor family, has been demonstrated to be involved in tumorigenesis of many human malignancies; however, its role in primary gallbladder carcinoma (PGC) is still largely unknown. The aim of this study was to investigate SOX4 expression in PGC and its prognostic significance. METHODS: From 1997 to 2006, 136 patients underwent resection for PGC. The median follow-up was 12.8 months. Immunostainings for SOX4 were performed on these archival tissues. The correlation of SOX4 expression with clinicopathological features including survival was analyzed. RESULTS: SOX4 was expressed in 75.0% (102/136) of PGC but not in the normal epithelium of the gallbladder. In addition, the over-expression of SOX4 was significantly associated with low histologic grade (P = 0.02), low pathologic T stage (P = 0.02), and early clinical stage (P = 0.03). The levels of SOX4 immunostainings in PGC tissues with positive nodal metastasis were also significantly lower than those without (P = 0.01). Moreover, Kaplan-Meier curves showed that SOX4 over-expression was significantly related to better overall (P = 0.008) and disease-free survival (P = 0.01). Furthermore, multivariate analyses showed that SOX4 expression was an independent risk factor for both overall (P = 0.03, hazard ratio, 3.682) and disease-free survival (P = 0.04, hazard ratio, 2.215). CONCLUSION: Our data indicate for the first time that the over-expression of SOX4 in PGC was significantly correlated with favorable clinicopathologic features and was an independent prognostic factor for better overall and disease-free survival in patients. Therefore, SOX4 might be an auxiliary parameter for predicting malignant behavior for PGC. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1534825818694957.","Source":"PubMed","category":"ANIMAL","training_data":"Clinicopathological significance of SOX4 expression in primary gallbladder carcinoma AIM: SOX4, as a member of the SRY-related HMG-box (SOX) transcription factor family, has been demonstrated to be involved in tumorigenesis of many human malignancies; however, its role in primary gallbladder carcinoma (PGC) is still largely unknown. The aim of this study was to investigate SOX4 expression in PGC and its prognostic significance. METHODS: From 1997 to 2006, 136 patients underwent resection for PGC. The median follow-up was 12.8 months. Immunostainings for SOX4 were performed on these archival tissues. The correlation of SOX4 expression with clinicopathological features including survival was analyzed. RESULTS: SOX4 was expressed in 75.0% (102/136) of PGC but not in the normal epithelium of the gallbladder. In addition, the over-expression of SOX4 was significantly associated with low histologic grade (P = 0.02), low pathologic T stage (P = 0.02), and early clinical stage (P = 0.03). The levels of SOX4 immunostainings in PGC tissues with positive nodal metastasis were also significantly lower than those without (P = 0.01). Moreover, Kaplan-Meier curves showed that SOX4 over-expression was significantly related to better overall (P = 0.008) and disease-free survival (P = 0.01). Furthermore, multivariate analyses showed that SOX4 expression was an independent risk factor for both overall (P = 0.03, hazard ratio, 3.682) and disease-free survival (P = 0.04, hazard ratio, 2.215). CONCLUSION: Our data indicate for the first time that the over-expression of SOX4 in PGC was significantly correlated with favorable clinicopathologic features and was an independent prognostic factor for better overall and disease-free survival in patients. Therefore, SOX4 might be an auxiliary parameter for predicting malignant behavior for PGC. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1534825818694957. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"defining perioperative risk hepatectomy based diagnosis resection extent outcomes hepatectomy assessed incompletely stratified extent resection diagnosis hypothesized operative risk better assessed stratifying diagnoses low high risk categories extent resection major minor resection categories accurately evaluate outcomes hepatectomy acs nsqip reviewed 30 day operative mortality major morbidity partial hepatectomy ph left hepatectomy lh right hepatectomy rh trisectionectomy ts mortality reviewed per diagnosis high risk defined diagnoses associated greatest mortality major minor resections defined comparison outcomes extent resection univariate analysis chi square tests tests fisher exact tests multivariable logistic regression utilized compare outcomes across groups among 7 043 patients greatest mortality observed hepatocellular carcinoma 5 2 cholangiocarcinoma 8 2 either intra extrahepatic classified high risk metastatic disease benign neoplasms gallbladder cancer mortality rate 1 3 0 5 1 0 respectively classified low risk ph lh similar statistically operative mortality major morbidity within respective diagnosis risk groups low risk ph vs lh high risk ph vs lh p 0 05 defined minor resections similarly rh ts similar operative mortality major morbidity within respective diagnosis risk groups low risk rh vs ts high risk rh vs ts p 0 05 defined major resections risks major morbidity mortality increased diagnoses extent resection minor resections mortality major morbidity 5 1 6 times greater respectively high risk diagnosis low risk diagnosis major resections mortality major morbidity 4 1 6 times greater respectively high risk diagnoses low risk diagnoses low risk diagnoses mortality major morbidity 2 9 1 7 times greater respectively major resections minor resections p 0 001 high risk diagnoses mortality major morbidity 2 3 1 7 times greater respectively major resections minor resections p 0 001 regardless extent resection high risk diagnoses independently associated mortality 3 2 3 1 respectively major morbidity 1 5 1 5 respectively risk hepatectomy better assessed stratified diagnostic risk extent resection accurate assessment outcomes significant implications preoperative planning informed consent resource utilization inter institutional comparisons stn","probabilities":0.9799733,"Title":"Defining Perioperative Risk After Hepatectomy Based On Diagnosis And Resection Extent","Abstract":"Outcomes after hepatectomy have been assessed incompletely and have not been stratified by both extent of resection and diagnosis. We hypothesized that operative risk is better assessed by stratifying diagnoses into low- and high-risk categories and extent of resection into major and minor resection categories to more accurately evaluate the outcomes after hepatectomy. ACS-NSQIP was reviewed for 30-day operative mortality and major morbidity after partial hepatectomy (PH), left hepatectomy (LH), right hepatectomy (RH), and trisectionectomy (TS). Mortality was reviewed per diagnosis. \"High Risk\" was defined as the diagnoses associated with the greatest mortality. Major and minor resections were defined by comparison of outcomes for extent of resection by univariate analysis. Chi-square tests, t tests, Fisher's exact tests, and multivariable logistic regression were utilized to compare the outcomes across groups. Among the 7,043 patients, the greatest mortality was observed with hepatocellular carcinoma (5.2%) and cholangiocarcinoma (8.2%), either intra- or extrahepatic, which were classified \"High Risk\". Metastatic disease, benign neoplasms, and gallbladder cancer had a mortality rate of 1.3, 0.5, and 1.0%, respectively, and were classified \"Low Risk\". PH and LH were similar statistically for operative mortality and major morbidity within respective diagnosis risk groups (Low Risk: PH vs. LH and High Risk: PH vs. LH; all p > 0.05) and were defined as \"Minor Resections\". Similarly, RH and TS had similar operative mortality and major morbidity within respective diagnosis risk groups (Low Risk: RH vs. TS and High Risk: RH vs. TS; all p > 0.05) and were defined as \"Major Resections\". Risks of major morbidity and mortality increased for both diagnoses and the extent of resection. With minor resections, mortality and major morbidity were 5 and 1.6 times greater respectively for high-risk diagnosis than for low-risk diagnosis. With major resections, mortality and major morbidity were 4 and 1.6 times greater, respectively, for high-risk diagnoses than low-risk diagnoses. With low-risk diagnoses, mortality and major morbidity were 2.9 and 1.7 times greater, respectively, for major resections than minor resections (p < 0.001). With high-risk diagnoses, mortality and major morbidity were 2.3 and 1.7 times greater, respectively, for major resections than minor resections (all p < 0.001). Regardless of the extent of resection, high-risk diagnoses were independently associated with mortality (OR = 3.2 and 3.1, respectively) and major morbidity (OR = 1.5 and 1.5, respectively). Risk of hepatectomy is better assessed when stratified by both the diagnostic risk and the extent of resection. Accurate assessment of these outcomes has significant implications for preoperative planning, informed consent, resource utilization, and inter-institutional comparisons.","Source":"STN","category":"HUMAN","training_data":"Defining Perioperative Risk After Hepatectomy Based On Diagnosis And Resection Extent Outcomes after hepatectomy have been assessed incompletely and have not been stratified by both extent of resection and diagnosis. We hypothesized that operative risk is better assessed by stratifying diagnoses into low- and high-risk categories and extent of resection into major and minor resection categories to more accurately evaluate the outcomes after hepatectomy. ACS-NSQIP was reviewed for 30-day operative mortality and major morbidity after partial hepatectomy (PH), left hepatectomy (LH), right hepatectomy (RH), and trisectionectomy (TS). Mortality was reviewed per diagnosis. \"High Risk\" was defined as the diagnoses associated with the greatest mortality. Major and minor resections were defined by comparison of outcomes for extent of resection by univariate analysis. Chi-square tests, t tests, Fisher's exact tests, and multivariable logistic regression were utilized to compare the outcomes across groups. Among the 7,043 patients, the greatest mortality was observed with hepatocellular carcinoma (5.2%) and cholangiocarcinoma (8.2%), either intra- or extrahepatic, which were classified \"High Risk\". Metastatic disease, benign neoplasms, and gallbladder cancer had a mortality rate of 1.3, 0.5, and 1.0%, respectively, and were classified \"Low Risk\". PH and LH were similar statistically for operative mortality and major morbidity within respective diagnosis risk groups (Low Risk: PH vs. LH and High Risk: PH vs. LH; all p > 0.05) and were defined as \"Minor Resections\". Similarly, RH and TS had similar operative mortality and major morbidity within respective diagnosis risk groups (Low Risk: RH vs. TS and High Risk: RH vs. TS; all p > 0.05) and were defined as \"Major Resections\". Risks of major morbidity and mortality increased for both diagnoses and the extent of resection. With minor resections, mortality and major morbidity were 5 and 1.6 times greater respectively for high-risk diagnosis than for low-risk diagnosis. With major resections, mortality and major morbidity were 4 and 1.6 times greater, respectively, for high-risk diagnoses than low-risk diagnoses. With low-risk diagnoses, mortality and major morbidity were 2.9 and 1.7 times greater, respectively, for major resections than minor resections (p < 0.001). With high-risk diagnoses, mortality and major morbidity were 2.3 and 1.7 times greater, respectively, for major resections than minor resections (all p < 0.001). Regardless of the extent of resection, high-risk diagnoses were independently associated with mortality (OR = 3.2 and 3.1, respectively) and major morbidity (OR = 1.5 and 1.5, respectively). Risk of hepatectomy is better assessed when stratified by both the diagnostic risk and the extent of resection. Accurate assessment of these outcomes has significant implications for preoperative planning, informed consent, resource utilization, and inter-institutional comparisons. STN","prediction_labels":"HUMAN"},{"cleaned":"high expression oct4 nanog predict poor prognosis intrahepatic cholangiocarcinoma patients curative resection oct4 nanog reported promote tumor progression several cancers effect intrahepatic cholangiocarcinoma icc unknown aim present study explore prognostic role oct4 nanog patients icc immunohistochemistry used detect expression oct4 nanog random cohort 116 icc patients validated another independent cohort 103 patients prognostic nomograms formulated os rfs prediction icc patients results showed oct4 nanog highly expressed icc tumor tissues identified independent prognostic factors patients os rfs significant positive correlation found oct4 nanog expression co expression oct4 nanog implied poorest os rfs icc patients nomograms comprising oct4 nanog achieved better predictive accuracy training validation cohorts compared ajcc 7th edition lcsgj stage os rfs prediction study support high expression oct4 nanog icc implies aggressive tumor behaviors suggest poor clinical prognosis emerges valuable biomarkers identifying patients high risk curative resection stn","probabilities":0.9285714,"Title":"High Expression Of Oct4 And Nanog Predict Poor Prognosis In Intrahepatic Cholangiocarcinoma Patients After Curative Resection","Abstract":"Oct4 and Nanog are reported to promote tumor progression in several cancers, but the effect on intrahepatic cholangiocarcinoma (ICC) is unknown. The aim of our present study was to explore the prognostic role of Oct4 and Nanog on patients with ICC. Immunohistochemistry was used to detect the expression of Oct4 and Nanog in a random cohort of 116 ICC patients, and validated in another independent cohort of 103 patients. Prognostic nomograms were formulated for OS and RFS prediction of ICC patients. Our results showed Oct4 and Nanog highly expressed in ICC tumor tissues and were identified as independent prognostic factors for patients' OS and RFS. Significant positive correlation was found between Oct4 and Nanog expression. Co-expression of Oct4 and Nanog implied the poorest OS and RFS in ICC patients. Our nomograms comprising Oct4 and Nanog achieved better predictive accuracy in training and validation cohorts compared with AJCC 7th edition and LCSGJ stage for OS and RFS prediction. Our study support the high expression of Oct4 and Nanog in ICC implies aggressive tumor behaviors and suggest a poor clinical prognosis, which emerges as valuable biomarkers for identifying patients at high risk after curative resection.","Source":"STN","category":"ANIMAL","training_data":"High Expression Of Oct4 And Nanog Predict Poor Prognosis In Intrahepatic Cholangiocarcinoma Patients After Curative Resection Oct4 and Nanog are reported to promote tumor progression in several cancers, but the effect on intrahepatic cholangiocarcinoma (ICC) is unknown. The aim of our present study was to explore the prognostic role of Oct4 and Nanog on patients with ICC. Immunohistochemistry was used to detect the expression of Oct4 and Nanog in a random cohort of 116 ICC patients, and validated in another independent cohort of 103 patients. Prognostic nomograms were formulated for OS and RFS prediction of ICC patients. Our results showed Oct4 and Nanog highly expressed in ICC tumor tissues and were identified as independent prognostic factors for patients' OS and RFS. Significant positive correlation was found between Oct4 and Nanog expression. Co-expression of Oct4 and Nanog implied the poorest OS and RFS in ICC patients. Our nomograms comprising Oct4 and Nanog achieved better predictive accuracy in training and validation cohorts compared with AJCC 7th edition and LCSGJ stage for OS and RFS prediction. Our study support the high expression of Oct4 and Nanog in ICC implies aggressive tumor behaviors and suggest a poor clinical prognosis, which emerges as valuable biomarkers for identifying patients at high risk after curative resection. STN","prediction_labels":"ANIMAL"},{"cleaned":"cxcr4 expression survival cancer system review meta analysis c x c chemokine receptor 4 cxcr4 frequently expressed various types cancer many agents cxcr4 clinical development currently despite variable data prognostic impact cxcr4 expression eighty five studies total 11 032 subjects included explore association cxcr4 progression free survival pfs overall survival os subjects cancer pooled analysis shows cxcr4 expression significantly associated poorer pfs hr 2 04 95 ci 1 72 2 42 os hr 1 94 95 ci 1 71 2 20 irrespective cancer types subgroup analysis indicates significant association cxcr4 shorter pfs hematological malignancy breast cancer colorectal cancer esophageal cancer renal cancer gynecologic cancer pancreatic cancer liver cancer prognostic effects remained consistent across age risk bias levels adjustment median follow period geographical area detection methods publication year size studies cxcr4 expression predicts unfavorable os hematological malignancy breast cancer colorectal cancer esophageal cancer head neck cancer renal cancer lung cancer gynecologic cancer liver cancer prostate cancer gallbladder cancer effects independence age levels adjustment publication year detection methods follow period conclusion cxcr4 expression associated poor prognosis cancer pubmed","probabilities":0.9799733,"Title":"CXCR4 over-expression and survival in cancer: a system review and meta-analysis","Abstract":"C-X-C chemokine receptor 4 (CXCR4) is frequently over-expressed in various types of cancer; many agents against CXCR4 are in clinical development currently despite variable data for the prognostic impact of CXCR4 expression. Here eighty-five studies with a total of 11,032 subjects were included to explore the association between CXCR4 and progression-free survival (PFS) or overall survival (OS) in subjects with cancer. Pooled analysis shows that CXCR4 over-expression is significantly associated with poorer PFS (HR 2.04; 95% CI, 1.72-2.42) and OS (HR=1.94; 95% CI, 1.71-2.20) irrespective of cancer types. Subgroup analysis indicates significant association between CXCR4 and shorter PFS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, renal cancer, gynecologic cancer, pancreatic cancer and liver cancer; the prognostic effects remained consistent across age, risk of bias, levels of adjustment, median follow-up period, geographical area, detection methods, publication year and size of studies. CXCR4 over-expression predicts unfavorable OS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, head and neck cancer, renal cancer, lung cancer, gynecologic cancer, liver cancer, prostate cancer and gallbladder cancer; these effects were independence of age, levels of adjustment, publication year, detection methods and follow-up period. In conclusion, CXCR4 over-expression is associated with poor prognosis in cancer.","Source":"PubMed","category":"HUMAN","training_data":"CXCR4 over-expression and survival in cancer: a system review and meta-analysis C-X-C chemokine receptor 4 (CXCR4) is frequently over-expressed in various types of cancer; many agents against CXCR4 are in clinical development currently despite variable data for the prognostic impact of CXCR4 expression. Here eighty-five studies with a total of 11,032 subjects were included to explore the association between CXCR4 and progression-free survival (PFS) or overall survival (OS) in subjects with cancer. Pooled analysis shows that CXCR4 over-expression is significantly associated with poorer PFS (HR 2.04; 95% CI, 1.72-2.42) and OS (HR=1.94; 95% CI, 1.71-2.20) irrespective of cancer types. Subgroup analysis indicates significant association between CXCR4 and shorter PFS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, renal cancer, gynecologic cancer, pancreatic cancer and liver cancer; the prognostic effects remained consistent across age, risk of bias, levels of adjustment, median follow-up period, geographical area, detection methods, publication year and size of studies. CXCR4 over-expression predicts unfavorable OS in hematological malignancy, breast cancer, colorectal cancer, esophageal cancer, head and neck cancer, renal cancer, lung cancer, gynecologic cancer, liver cancer, prostate cancer and gallbladder cancer; these effects were independence of age, levels of adjustment, publication year, detection methods and follow-up period. In conclusion, CXCR4 over-expression is associated with poor prognosis in cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"helicobacter species possible risk factors cholangiocarcinoma several infectious agents considered causes cancer human mainly hepatitis b c viruses high risk human pailloma viruses helicobacter pylori clonorchis sinensis opisthorchis viverrini described evident research association helicobacter spp biliary tract cancer particularly cholangiocarcinoma cca global epidemiological studies suggested helicobacter spp possible risk factors biliary tract diseases molecular studies support linkage helicobacter spp cca development h pylori h bilis h hepaticus found cca common species h pylori h bilis type cca associated helicobacter spp include extrahepatic cca common bile duct cancer present however results different regions materials methods sub sites cancer controls consistent thus introducing heterogeneity therefore comparison co helicobacter spp cca countries low high incident cca required settle question furthermore clarifying variation role helicobacter species cca including pathogenesis cca enhanced biliary cell inflammation proliferation necessary pubmed","probabilities":1.0,"Title":"Helicobacter Species are Possible Risk Factors of Cholangiocarcinoma","Abstract":"Several infectious agents are considered to be causes of cancer in human, mainly hepatitis B and C viruses, high-risk human pailloma viruses, Helicobacter pylori, Clonorchis sinensis, and Opisthorchis viverrini. Here we described the evident research and the association between Helicobacter spp. and biliary tract cancer particularly cholangiocarcinoma (CCA). Global epidemiological studies have suggested that Helicobacter spp. are possible risk factors for biliary tract diseases. Molecular studies support a linkage of Helicobacter spp. with CCA development. H. pylori, H. bilis, and H. hepaticus, are found in CCA, but the most common species are H. pylori and H. bilis. The type of CCA are associated with Helicobacter spp. include extrahepatic CCA, and common bile duct cancer. Up to the present, however, the results from different regions, materials and methods, sub-sites of cancer, and controls have not been consistent, thus introducing heterogeneity. Therefore, a comparison between co-Helicobacter spp.-CCA in the countries with low and high incident of CCA is required to settle the question. Furthermore, clarifying variation in the role of Helicobacter species in this CCA, including pathogenesis of CCA through enhanced biliary cell inflammation and proliferation, is necessary.","Source":"PubMed","category":"HUMAN","training_data":"Helicobacter Species are Possible Risk Factors of Cholangiocarcinoma Several infectious agents are considered to be causes of cancer in human, mainly hepatitis B and C viruses, high-risk human pailloma viruses, Helicobacter pylori, Clonorchis sinensis, and Opisthorchis viverrini. Here we described the evident research and the association between Helicobacter spp. and biliary tract cancer particularly cholangiocarcinoma (CCA). Global epidemiological studies have suggested that Helicobacter spp. are possible risk factors for biliary tract diseases. Molecular studies support a linkage of Helicobacter spp. with CCA development. H. pylori, H. bilis, and H. hepaticus, are found in CCA, but the most common species are H. pylori and H. bilis. The type of CCA are associated with Helicobacter spp. include extrahepatic CCA, and common bile duct cancer. Up to the present, however, the results from different regions, materials and methods, sub-sites of cancer, and controls have not been consistent, thus introducing heterogeneity. Therefore, a comparison between co-Helicobacter spp.-CCA in the countries with low and high incident of CCA is required to settle the question. Furthermore, clarifying variation in the role of Helicobacter species in this CCA, including pathogenesis of CCA through enhanced biliary cell inflammation and proliferation, is necessary. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cytoplasmic hu antigen r hur expression associated poor survival patients surgically resected cholangiocarcinoma treated adjuvant gemcitabine based chemotherapy background hu antigen r hur rna binding protein regulates stability translation nucleus cytoplasm translocation messenger rnas mrnas objective aim study investigate prognostic significance hur cholangiocarcinoma patients received adjuvant gemcitabine based chemotherapy agc surgical resection methods nuclear cytoplasmic hur expression investigated immunohistochemically 131 patients resected cholangiocarcinoma including 91 patients administered agc 40 patients receive adjuvant chemotherapy correlation hur expression survival evaluated statistical analysis results high nuclear cytoplasmic hur expression observed 67 51 45 34 patients respectively cytoplasmic hur expression significantly associated lymph node metastasis p 0 01 high cytoplasmic hur expression significantly associated poor disease free survival dfs p 0 03 overall survival os p 0 001 91 patients received agc 40 patients receive agc dfs p 0 17 os p 0 07 multivariate analysis patients received agc high cytoplasmic hur expression independent predictor poor dfs hazard ratio hr 1 77 p 0 04 os hr 2 09 p 0 02 nuclear hur expression affect survival enrolled patients conclusions high cytoplasmic hur expression closely associated efficacy agc patients cholangiocarcinoma current findings warrant investigations optimize adjuvant chemotherapy regimens resectable cholangiocarcinoma stn","probabilities":0.9799733,"Title":"Cytoplasmic Hu-Antigen R (Hur) Expression Is Associated With Poor Survival In Patients With Surgically Resected Cholangiocarcinoma Treated With Adjuvant Gemcitabine-Based Chemotherapy","Abstract":"Background: Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). \r\n\r\n Objective: The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. \r\n\r\n Methods: Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. \r\n\r\n Results: High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. \r\n\r\n Conclusions: High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Cytoplasmic Hu-Antigen R (Hur) Expression Is Associated With Poor Survival In Patients With Surgically Resected Cholangiocarcinoma Treated With Adjuvant Gemcitabine-Based Chemotherapy Background: Hu-antigen R (HuR) is an RNA-binding protein that regulates the stability, translation, and nucleus-to-cytoplasm translocation of messenger RNAs (mRNAs). \r\n\r\n Objective: The aim of this study was to investigate the prognostic significance of HuR in cholangiocarcinoma patients who received adjuvant gemcitabine-based chemotherapy (AGC) after surgical resection. \r\n\r\n Methods: Nuclear and cytoplasmic HuR expression was investigated immunohistochemically in 131 patients with resected cholangiocarcinoma, including 91 patients administered AGC and 40 patients who did not receive adjuvant chemotherapy. The correlation between HuR expression and survival was evaluated by statistical analysis. \r\n\r\n Results: High nuclear and cytoplasmic HuR expression was observed in 67 (51%) and 45 (34%) patients, respectively. Cytoplasmic HuR expression was significantly associated with lymph node metastasis (p < 0.01), while high cytoplasmic HuR expression was significantly associated with poor disease-free survival [DFS] (p = 0.03) and overall survival [OS] (p = 0.001) in the 91 patients who received AGC, but not in the 40 patients who did not receive AGC (DFS p = 0.17; OS p = 0.07). In the multivariate analysis of patients who received AGC, high cytoplasmic HuR expression was an independent predictor of poor DFS (hazard ratio [HR] 1.77; p = 0.04) and OS (HR 2.09; p = 0.02). Nuclear HuR expression did not affect the survival of enrolled patients. \r\n\r\n Conclusions: High cytoplasmic HuR expression was closely associated with the efficacy of AGC in patients with cholangiocarcinoma. The current findings warrant further investigations to optimize adjuvant chemotherapy regimens for resectable cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"soluble urokinase plasminogen activator receptor supar predicts outcome resection biliary tract cancer background aims surgical resection potentially curative therapy patients biliary tract cancer btc 5 year survival rates tumor resection remained 30 corroborating need better stratification tools identify ideal surgical candidates soluble urokinase plasminogen activator receptor supar represents mediator inflammation associated distinct types cancer study evaluated potential role supar novel biomarker patients undergoing btc resection methods tumor expression upar analyzed immunohistochemistry 108 btc samples serum levels supar analyzed elisa training validation cohort comprising total 117 patients btc 76 healthy controls results high tumoral upar expression associated adverse outcome btc resection accordingly circulating levels supar significantly elevated patients btc compared healthy controls well patients primary sclerosing cholangitis using small training set established optimal prognostic supar cut value 3 72 ng ml patients btc importantly preoperative supar serum levels cut value associated significantly impaired overall survival training validation cohort multivariate cox regression analysis including various clinicopathological parameters tumor stage markers inflammation organ dysfunction well tumor markers revealed circulating supar levels independent prognostic marker following btc resection finally high preoperative supar levels indicative acute kidney injury tumor resection conclusion circulating supar represents previously unrecognized biomarker patients resectable btc might help preoperatively identify ideal candidates liver surgery lay summary surgical resection represents curative treatment option patients biliary tract cancer patients benefit extent terms overall survival provide evidence serum levels inflammatory mediator supar indicative patient postoperative outcome might thus help identify ideal surgical candidates stn","probabilities":0.9799733,"Title":"Soluble Urokinase Plasminogen Activator Receptor (Supar) Predicts Outcome After Resection Of Biliary Tract Cancer","Abstract":"Background & aims: Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection. \r\n\r\n Methods: Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls. \r\n\r\n Results: High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection. \r\n\r\n Conclusion: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery. \r\n\r\n Lay summary: Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates.","Source":"STN","category":"HUMAN","training_data":"Soluble Urokinase Plasminogen Activator Receptor (Supar) Predicts Outcome After Resection Of Biliary Tract Cancer Background & aims: Surgical resection is the only potentially curative therapy for patients with biliary tract cancer (BTC), but 5-year survival rates after tumor resection have remained below 30%, corroborating the need for better stratification tools to identify the ideal surgical candidates. The soluble urokinase plasminogen activator receptor (suPAR) represents a mediator of inflammation and has been associated with distinct types of cancer. In this study, we evaluated a potential role of suPAR as a novel biomarker in patients undergoing BTC resection. \r\n\r\n Methods: Tumor expression of uPAR was analyzed by immunohistochemistry in 108 BTC samples. Serum levels of suPAR were analyzed by ELISA in a training and validation cohort comprising a total of 117 patients with BTC and 76 healthy controls. \r\n\r\n Results: High tumoral uPAR expression was associated with an adverse outcome after BTC resection. Accordingly, circulating levels of suPAR were significantly elevated in patients with BTC compared to healthy controls, as well as in patients with primary sclerosing cholangitis. Using a small training set, we established an optimal prognostic suPAR cut-off value of 3.72 ng/ml for patients with BTC. Importantly, preoperative suPAR serum levels above this cut-off value were associated with significantly impaired overall survival in both the training and validation cohort. Multivariate Cox-regression analysis including various clinicopathological parameters such as tumor stage, markers of inflammation and organ dysfunction, as well as tumor markers, revealed circulating suPAR levels as an independent prognostic marker following BTC resection. Finally, high preoperative suPAR levels were indicative of acute kidney injury after tumor resection. \r\n\r\n Conclusion: Circulating suPAR represents a previously unrecognized biomarker in patients with resectable BTC, which might help to preoperatively identify the ideal candidates for liver surgery. \r\n\r\n Lay summary: Surgical resection represents the only curative treatment option for patients with biliary tract cancer, but not all patients benefit to the same extent in terms of overall survival. Here, we provide evidence that serum levels of an inflammatory mediator (suPAR) are indicative of a patient's postoperative outcome and might thus help to identify the ideal surgical candidates. STN","prediction_labels":"HUMAN"},{"cleaned":"human epidermal growth factor receptor 2 epidermal growth factor receptor c met overexpression survival biliary tract cancer meta analysis background tyrosine kinase growth factor receptors tkgfrs play important role progression cancer variety studies investigated clinicopathologic correlation receptors influences patient survival different types cancer members tkgfrs biomarkers c met epidermal growth factor receptor egfr human epidermal growth factor receptor 2 2 extensively investigated biliary tract cancer btc however prognostic value still controversial study aimed evaluate prognostic significance three markers btc patients based published studies correlation high expression markers clinical parameters overall survival os assumed paper materials methods including pubmed embase china national knowledge infrastructure springer comprehensive search related literature published chinese english done finally 31 studies selected research results surprisingly meta analysis indicated 2 high expression correlated age gender primary tumor tumor node metastasis tnm stage lymph node status differentiation also found egfr high expression associated parameters age gender tnm stage differentiation lymph node status c met high expression associated age differentiation gender tnm stage lymph node status addition study showed 2 egfr c met high expression adverse influence os btc pooled hazard ratio 2 egfr c met statistically significant conclusion present meta analysis indicated egfr 2 high expression little impact os patients btc c met high expression influenced os patients btc large extent however c met egfr 2 expression show correlation clinical parameters c met may potential therapeutic target btc pubmed","probabilities":0.75,"Title":"Human epidermal growth factor receptor 2, epidermal growth factor receptor, and c-MET overexpression and survival in biliary tract cancer: A meta-analysis","Abstract":"BACKGROUND: Tyrosine kinase growth factor receptors (TKGFRs) play an important role in the progression of cancer. A variety of studies have investigated the clinicopathologic correlation of these receptors and their influences on patient survival in different types of cancer. As the members of TKGFRs, the biomarkers c-MET, epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER-2) have been extensively investigated in biliary tract cancer (BTC). However, their prognostic value is still controversial. Our study aimed to evaluate the prognostic significance of the three markers in BTC patients based on the published studies. The correlation between high expression of these markers and clinical parameters or overall survival (OS) has been assumed in this paper. MATERIALS AND METHODS: Including PubMed, EMBASE, China National Knowledge Infrastructure, and Springer, a comprehensive search for the related literature published in Chinese and English has been done. Finally, 31 studies were selected in our research. RESULTS: Surprisingly, the meta-analysis indicated that HER-2 high expression was not correlated with age, gender, primary tumor, tumor node metastasis (TNM) stage, lymph node status, and differentiation. We also found that EGFR high expression was not associated with the parameters, such as age, gender, TNM stage, differentiation, or lymph node status. c-MET high-expression was not associated with age, differentiation, gender, TNM stage, or lymph node status. In addition, our study showed that HER-2, EGFR, and c-MET high expression had an adverse influence on OS in BTC, the pooled hazard ratio for HER-2, EGFR, and c-MET was statistically significant. CONCLUSION: The present meta-analysis indicated that EGFR and HER-2 high expression have little impact on OS in patients with BTC while c-MET high expression influenced OS in patients with BTC to a large extent. However, c-MET, EGFR, and HER-2 expression did not show any correlation with those clinical parameters. c-MET may be a potential therapeutic target for BTC.","Source":"PubMed","category":"HUMAN","training_data":"Human epidermal growth factor receptor 2, epidermal growth factor receptor, and c-MET overexpression and survival in biliary tract cancer: A meta-analysis BACKGROUND: Tyrosine kinase growth factor receptors (TKGFRs) play an important role in the progression of cancer. A variety of studies have investigated the clinicopathologic correlation of these receptors and their influences on patient survival in different types of cancer. As the members of TKGFRs, the biomarkers c-MET, epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER-2) have been extensively investigated in biliary tract cancer (BTC). However, their prognostic value is still controversial. Our study aimed to evaluate the prognostic significance of the three markers in BTC patients based on the published studies. The correlation between high expression of these markers and clinical parameters or overall survival (OS) has been assumed in this paper. MATERIALS AND METHODS: Including PubMed, EMBASE, China National Knowledge Infrastructure, and Springer, a comprehensive search for the related literature published in Chinese and English has been done. Finally, 31 studies were selected in our research. RESULTS: Surprisingly, the meta-analysis indicated that HER-2 high expression was not correlated with age, gender, primary tumor, tumor node metastasis (TNM) stage, lymph node status, and differentiation. We also found that EGFR high expression was not associated with the parameters, such as age, gender, TNM stage, differentiation, or lymph node status. c-MET high-expression was not associated with age, differentiation, gender, TNM stage, or lymph node status. In addition, our study showed that HER-2, EGFR, and c-MET high expression had an adverse influence on OS in BTC, the pooled hazard ratio for HER-2, EGFR, and c-MET was statistically significant. CONCLUSION: The present meta-analysis indicated that EGFR and HER-2 high expression have little impact on OS in patients with BTC while c-MET high expression influenced OS in patients with BTC to a large extent. However, c-MET, EGFR, and HER-2 expression did not show any correlation with those clinical parameters. c-MET may be a potential therapeutic target for BTC. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"prognostic impact differentiation invasive front biliary tract cancer background invasive front tumor provide prognostic information many cancers investigated prognostic morphological factors invasive front including tumor differentiation dif inv tumor budding bud biliary tract cancer btc methods resected specimen 299 btc patients examined intrahepatic cholangiocarcinoma extrahepatic cholangiocarcinoma gallbladder cancer ampulla vater cancer found 16 48 17 19 respectively dif inv grade g 3 bud foci 5 found 47 10 tumor dif inv g3 showed high frequencies bud vascular invasion ve nodal metastasis ln compared tumor dif inv g1 2 bud 21 vs 0 ve 71 vs 50 ln 52 vs 36 multivariate analysis revealed independent predictors dif inv g3 hr 1 71 bud foci 5 hr 2 14 ve hr 1 56 ln hr 2 59 overall survival positive resection margin hr 1 71 dif inv g3 hr 1 75 ve hr 1 50 ln hr 2 19 relapse free survival conclusion poor differentiation invasive front tumor associated poor prognosis early relapse btc patients pubmed","probabilities":0.9799733,"Title":"The prognostic impact of differentiation at the invasive front of biliary tract cancer","Abstract":"BACKGROUND: The invasive front of tumor can provide prognostic information in many cancers. We investigated the prognostic morphological factors at the invasive front including tumor differentiation (Dif(inv) ) and tumor budding (Bud) in biliary tract cancer (BTC). METHODS: The resected specimen from the 299 BTC patients were examined. Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer were found in 16%, 48%, 17%, and 19%, respectively. Dif(inv) grade (G) 3 and Bud foci ≥5 were found in 47% and 10%. Tumor with Dif(inv) G3 showed the high frequencies of Bud, vascular invasion (Ve) and nodal metastasis (LN) compared to tumor with Dif(inv) G1/2 (Bud: 21% vs 0%, Ve: 71% vs 50%, LN: 52% vs 36%). Multivariate analysis revealed that the independent predictors were Dif(inv) G3 (HR: 1.71), Bud foci ≥5 (HR: 2.14), Ve (HR: 1.56) and LN (HR: 2.59) in overall survival and were positive resection margin (HR: 1.71), Dif(inv) G3 (HR: 1.75), Ve (HR: 1.50), and LN (HR: 2.19) in relapse free survival. CONCLUSION: Poor differentiation at the invasive front of tumor was associated with poor prognosis and early relapse in BTC patients.","Source":"PubMed","category":"HUMAN","training_data":"The prognostic impact of differentiation at the invasive front of biliary tract cancer BACKGROUND: The invasive front of tumor can provide prognostic information in many cancers. We investigated the prognostic morphological factors at the invasive front including tumor differentiation (Dif(inv) ) and tumor budding (Bud) in biliary tract cancer (BTC). METHODS: The resected specimen from the 299 BTC patients were examined. Intrahepatic cholangiocarcinoma, extrahepatic cholangiocarcinoma, gallbladder cancer, and ampulla of Vater cancer were found in 16%, 48%, 17%, and 19%, respectively. Dif(inv) grade (G) 3 and Bud foci ≥5 were found in 47% and 10%. Tumor with Dif(inv) G3 showed the high frequencies of Bud, vascular invasion (Ve) and nodal metastasis (LN) compared to tumor with Dif(inv) G1/2 (Bud: 21% vs 0%, Ve: 71% vs 50%, LN: 52% vs 36%). Multivariate analysis revealed that the independent predictors were Dif(inv) G3 (HR: 1.71), Bud foci ≥5 (HR: 2.14), Ve (HR: 1.56) and LN (HR: 2.59) in overall survival and were positive resection margin (HR: 1.71), Dif(inv) G3 (HR: 1.75), Ve (HR: 1.50), and LN (HR: 2.19) in relapse free survival. CONCLUSION: Poor differentiation at the invasive front of tumor was associated with poor prognosis and early relapse in BTC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value metastatic lymph node ratio patients resectable carcinoma ampulla vater patients carcinoma ampulla vater cav better outcomes among periampullary malignancies however little known metastatic lymph node ratio lnr prognostic factor resectable cav retrospectively reviewed cav patients undergoing curative surgery analyzed prognostic factors total 212 cav patients received radical surgery chang gung memorial hospital linkou 2000 2010 admitted study lymph node ratio defined number metastatic lymph nodes lns divided total number lns removed patients demographic data comorbidities operation type tumor features analyzed retrospectively survival prediction patients median age patients 62 years 57 patients men surgical procedure standard pancreaticoduodenectomy pylorus preserving pancreaticoduodenectomy 53 47 patients respectively median follow duration 32 6 months 50 patients died end study median overall survival time os disease free survival time dfs 65 8 33 7 months respectively multivariate analysis patients metastatic lnr 0 056 significantly poor prognosis os dfs metastatic lnr 0 056 predicted poor dfs os cav patients radical surgery greater awareness impact metastatic lnr may help clinicians provide appropriate adjuvant treatment high risk cav patients pubmed","probabilities":0.9799733,"Title":"Prognostic Value of the Metastatic Lymph Node Ratio in Patients With Resectable Carcinoma of Ampulla of Vater","Abstract":"Patients with carcinoma of the ampulla of Vater (CAV) have better outcomes among periampullary malignancies. However, little is known about the metastatic lymph node ratio (LNR) as a prognostic factor for resectable CAV. We retrospectively reviewed our CAV patients undergoing curative surgery and analyzed their prognostic factors.A total of 212 CAV patients who received radical surgery at Chang Gung Memorial Hospital, Linkou, between 2000 and 2010 were admitted in this study. The lymph node ratio was defined as the number of metastatic lymph nodes (LNs) divided by the total number of LNs removed. The patients' demographic data, comorbidities, operation type, and tumor features were analyzed retrospectively for survival prediction of patients.The median age of the patients was 62 years, and 57% of the patients were men. The surgical procedure was standard pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy in 53% and 47% of the patients, respectively. The median follow-up duration was 32.6 months, and 50% of the patients had died by the end of the study. The median overall survival time (OS) and disease-free survival time (DFS) were 65.8 and 33.7 months, respectively. In multivariate analysis, patients with a metastatic LNR >0.056 had a significantly poor prognosis in both OS and DFS.A metastatic LNR >0.056 predicted a poor DFS and OS in CAV patients after radical surgery. Greater awareness on the impact of metastatic LNR may help clinicians provide appropriate adjuvant treatment for high-risk CAV patients.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Value of the Metastatic Lymph Node Ratio in Patients With Resectable Carcinoma of Ampulla of Vater Patients with carcinoma of the ampulla of Vater (CAV) have better outcomes among periampullary malignancies. However, little is known about the metastatic lymph node ratio (LNR) as a prognostic factor for resectable CAV. We retrospectively reviewed our CAV patients undergoing curative surgery and analyzed their prognostic factors.A total of 212 CAV patients who received radical surgery at Chang Gung Memorial Hospital, Linkou, between 2000 and 2010 were admitted in this study. The lymph node ratio was defined as the number of metastatic lymph nodes (LNs) divided by the total number of LNs removed. The patients' demographic data, comorbidities, operation type, and tumor features were analyzed retrospectively for survival prediction of patients.The median age of the patients was 62 years, and 57% of the patients were men. The surgical procedure was standard pancreaticoduodenectomy and pylorus-preserving pancreaticoduodenectomy in 53% and 47% of the patients, respectively. The median follow-up duration was 32.6 months, and 50% of the patients had died by the end of the study. The median overall survival time (OS) and disease-free survival time (DFS) were 65.8 and 33.7 months, respectively. In multivariate analysis, patients with a metastatic LNR >0.056 had a significantly poor prognosis in both OS and DFS.A metastatic LNR >0.056 predicted a poor DFS and OS in CAV patients after radical surgery. Greater awareness on the impact of metastatic LNR may help clinicians provide appropriate adjuvant treatment for high-risk CAV patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiology gallbladder disease abstract available google scholar","probabilities":0.9799733,"Title":"Epidemiology Of Gallbladder Disease","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology Of Gallbladder Disease Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"global dna methylation hydroxymethylation differ hepatocellular carcinoma cholangiocarcinoma relate survival rate addition dna methylation hydroxymethylation dna recognized novel epigenetic mark primary liver cancers e hepatocellular carcinoma hcc cholangiocarcinoma cc highly prevalent epigenetically poorly characterized far present study measured global methylcytosine mcyt hydroxymethylcytosine hmcyt hcc cc tissues peripheral blood mononuclear cell pbmc dna define mcyt hmcyt status accordingly survival rate mcyt hmcyt measured liquid chromatography tandem mass spectrometry method neoplastic homologous nonneoplastic tissues e liver gallbladder pbmcs 31 hcc 16 cc patients content mcyt notably lower hcc cc tissues 3 97 versus 5 26 respectively p 0 0001 significantly reduced mcyt also detected hcc compared nonneoplastic tissue 3 97 versus 4 82 mcyt respectively p 0 0001 difference found cc versus homologous nonneoplastic tissue hydroxymethylation significantly decreased hcc versus nonneoplastic liver tissue 0 044 versus 0 128 respectively p 0 0001 cc versus liver gallbladder nonneoplastic tissue 0 030 versus 0 124 p 0 026 0 030 versus 0 123 p 0 006 respectively survival rate evaluated according mcyt pbmc content kaplan meier analysis patients mcyt 5 59 significantly higher life expectancy mcyt 5 59 p 0 034 follow period 48 months conclusion significant dna hypomethylation distinguishes hcc cc dna hypo hydroxymethylation characterizes hcc cc pbmc dna mcyt content 5 59 relates favorable outcome primary liver cancers pubmed","probabilities":0.962963,"Title":"Global DNA methylation and hydroxymethylation differ in hepatocellular carcinoma and cholangiocarcinoma and relate to survival rate","Abstract":"In addition to DNA methylation, hydroxymethylation of DNA is recognized as a novel epigenetic mark. Primary liver cancers, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), are highly prevalent but epigenetically poorly characterized, so far. In the present study we measured global methylcytosine (mCyt) and hydroxymethylcytosine (hmCyt) in HCC and CC tissues and in peripheral blood mononuclear cell (PBMC) DNA to define mCyt and hmCyt status and, accordingly, the survival rate. Both mCyt and hmCyt were measured by a liquid chromatography/tandem mass spectrometry method in neoplastic and homologous nonneoplastic tissues, i.e., liver and gallbladder, and in PBMCs of 31 HCC and 16 CC patients. Content of mCyt was notably lower in HCC than in CC tissues (3.97% versus 5.26%, respectively; P < 0.0001). Significantly reduced mCyt was also detected in HCC compared to nonneoplastic tissue (3.97% versus 4.82% mCyt, respectively; P < 0.0001), but no such difference was found for CC versus homologous nonneoplastic tissue. Hydroxymethylation was significantly decreased in HCC versus nonneoplastic liver tissue (0.044 versus 0.128, respectively; P < 0.0001) and in CC versus both liver and gallbladder nonneoplastic tissue (0.030 versus 0.124, P = 0.026, and 0.030 versus 0.123, P = 0.006, respectively). When the survival rate was evaluated according to mCyt PBMC content by Kaplan-Meier analysis, patients with mCyt ≥5.59% had a significantly higher life expectancy than those with mCyt <5.59% (P = 0.034) at a follow-up period up to 48 months. CONCLUSION: A significant DNA hypomethylation distinguishes HCC from CC, while DNA hypo-hydroxymethylation characterizes both HCC and CC, and a PBMC DNA mCyt content ≥5.59% relates to a favorable outcome in primary liver cancers.","Source":"PubMed","category":"ANIMAL","training_data":"Global DNA methylation and hydroxymethylation differ in hepatocellular carcinoma and cholangiocarcinoma and relate to survival rate In addition to DNA methylation, hydroxymethylation of DNA is recognized as a novel epigenetic mark. Primary liver cancers, i.e., hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), are highly prevalent but epigenetically poorly characterized, so far. In the present study we measured global methylcytosine (mCyt) and hydroxymethylcytosine (hmCyt) in HCC and CC tissues and in peripheral blood mononuclear cell (PBMC) DNA to define mCyt and hmCyt status and, accordingly, the survival rate. Both mCyt and hmCyt were measured by a liquid chromatography/tandem mass spectrometry method in neoplastic and homologous nonneoplastic tissues, i.e., liver and gallbladder, and in PBMCs of 31 HCC and 16 CC patients. Content of mCyt was notably lower in HCC than in CC tissues (3.97% versus 5.26%, respectively; P < 0.0001). Significantly reduced mCyt was also detected in HCC compared to nonneoplastic tissue (3.97% versus 4.82% mCyt, respectively; P < 0.0001), but no such difference was found for CC versus homologous nonneoplastic tissue. Hydroxymethylation was significantly decreased in HCC versus nonneoplastic liver tissue (0.044 versus 0.128, respectively; P < 0.0001) and in CC versus both liver and gallbladder nonneoplastic tissue (0.030 versus 0.124, P = 0.026, and 0.030 versus 0.123, P = 0.006, respectively). When the survival rate was evaluated according to mCyt PBMC content by Kaplan-Meier analysis, patients with mCyt ≥5.59% had a significantly higher life expectancy than those with mCyt <5.59% (P = 0.034) at a follow-up period up to 48 months. CONCLUSION: A significant DNA hypomethylation distinguishes HCC from CC, while DNA hypo-hydroxymethylation characterizes both HCC and CC, and a PBMC DNA mCyt content ≥5.59% relates to a favorable outcome in primary liver cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"mitochondrial pyruvate carrier modulates epithelial mesenchymal transition cholangiocarcinoma intrahepatic cholangiocarcinoma icc known high malignant potential high recurrence rate icc poor prognosis even complete tumor resection compared normal differentiated cells cancer cells altered metabolism supporting survival severe conditions cancer cells acquire additional malignant potential result metabolic alteration thus molecules known involved cancer metabolism novel therapeutic targets mitochondrial pyruvate carrier mpc recently discovered pyruvate transporter located mitochondrial inner membrane although mpc composed two subunits reported mpc1 subunit specifically associated poor prognosis several cancers including colorectal prostate cancer however studies assessed clinical significance mpc1 molecular mechanisms underlying influence cancer progression well understood study aimed clarify function mpc1 affects malignant potential icc expression mpc1 icc clinical specimens determined immunohistochemistry addition correlations mpc1 expression survival rate well various clinicopathological parameters assessed low mpc1 expression correlated poor icc prognosis correlated tumor invasion distant metastasis phenomena closely associated epithelial mesenchymal transition emt therefore investigated impact altering mpc1 gene expression malignant potential cancer cells using biliary tract cancer cell lines vitro expression mpc1 downregulated cells induced undergo emt following treatment tgf furthermore inhibition mpc1 expression induced emt cancer cells overexpression mpc1 suppressed migration tumor cells results indicated mpc1 novel therapeutic target cancers pubmed","probabilities":0.875,"Title":"Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma (ICC) is known to have a high malignant potential. Because of its high recurrence rate, ICC has a poor prognosis even after complete tumor resection. Compared with normal differentiated cells, cancer cells have an altered metabolism for supporting their survival in severe conditions. Cancer cells acquire additional malignant potential as a result of this metabolic alteration. Thus, the molecules known to be involved in cancer metabolism, could be novel therapeutic targets. The mitochondrial pyruvate carrier (MPC) is a recently discovered pyruvate transporter, which is located in the mitochondrial inner membrane. Although MPC is composed of two subunits, it has been reported that the MPC1 subunit is specifically associated with poor prognosis in several cancers, including colorectal and prostate cancer. However, only a few studies have assessed the clinical significance of MPC1 and the molecular mechanisms underlying its influence on cancer progression are not well understood. This study aimed to clarify the function of MPC1 that affects the malignant potential of ICC. The expression of MPC1 in ICC clinical specimens was determined by immunohistochemistry. In addition, the correlations between MPC1 expression and the survival rate, as well as various clinicopathological parameters were assessed. Low MPC1 expression correlated with poor ICC prognosis and was correlated with tumor invasion and distant metastasis. Both these phenomena are closely associated with the epithelial-mesenchymal transition (EMT). Therefore, we investigated the impact of altering the MPC1 gene expression on the malignant potential of cancer cells using biliary tract cancer cell lines in vitro. The expression of MPC1 was downregulated in the cells induced to undergo EMT following treatment with TGF-β. Furthermore, the inhibition of MPC1 expression induced EMT in cancer cells, and the overexpression of MPC1 suppressed the migration of tumor cells. These results indicated that MPC1 could be a novel therapeutic target in some cancers.","Source":"PubMed","category":"ANIMAL","training_data":"Mitochondrial pyruvate carrier modulates the epithelial-mesenchymal transition in cholangiocarcinoma Intrahepatic cholangiocarcinoma (ICC) is known to have a high malignant potential. Because of its high recurrence rate, ICC has a poor prognosis even after complete tumor resection. Compared with normal differentiated cells, cancer cells have an altered metabolism for supporting their survival in severe conditions. Cancer cells acquire additional malignant potential as a result of this metabolic alteration. Thus, the molecules known to be involved in cancer metabolism, could be novel therapeutic targets. The mitochondrial pyruvate carrier (MPC) is a recently discovered pyruvate transporter, which is located in the mitochondrial inner membrane. Although MPC is composed of two subunits, it has been reported that the MPC1 subunit is specifically associated with poor prognosis in several cancers, including colorectal and prostate cancer. However, only a few studies have assessed the clinical significance of MPC1 and the molecular mechanisms underlying its influence on cancer progression are not well understood. This study aimed to clarify the function of MPC1 that affects the malignant potential of ICC. The expression of MPC1 in ICC clinical specimens was determined by immunohistochemistry. In addition, the correlations between MPC1 expression and the survival rate, as well as various clinicopathological parameters were assessed. Low MPC1 expression correlated with poor ICC prognosis and was correlated with tumor invasion and distant metastasis. Both these phenomena are closely associated with the epithelial-mesenchymal transition (EMT). Therefore, we investigated the impact of altering the MPC1 gene expression on the malignant potential of cancer cells using biliary tract cancer cell lines in vitro. The expression of MPC1 was downregulated in the cells induced to undergo EMT following treatment with TGF-β. Furthermore, the inhibition of MPC1 expression induced EMT in cancer cells, and the overexpression of MPC1 suppressed the migration of tumor cells. These results indicated that MPC1 could be a novel therapeutic target in some cancers. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"prospective study metabolic risk factors gallbladder cancer metabolic syndrome cancer collaborative study objective investigate association metabolic risk factors individually combination risk gallbladder cancer gbc methods metabolic syndrome cancer project includes cohorts norway austria sweden data 578 700 men women used cox proportional hazard regression models calculate relative risks gbc body mass index bmi blood pressure plasma levels glucose cholesterol triglycerides continuous standardised variables standardised sum metabolic syndrome mets z score risk estimates corrected random error measurements results average follow 12 0 years sd 7 8 184 primary gallbladder cancers diagnosed relative risk gallbladder cancer per unit increment z score adjusted age smoking status bmi except bmi stratified birth year sex sub cohorts bmi 1 31 95 confidence interval 1 11 1 57 blood glucose 1 76 1 10 2 85 analysis showed effect bmi gbc risk larger among women premenopausal age group 1 84 1 23 2 78 compared postmenopausal age group 1 29 0 93 1 79 metabolic factors significant association found mid blood pressure 0 96 0 71 1 31 cholesterol 0 84 0 66 1 06 serum triglycerides 1 16 0 82 1 64 relative risk per one unit increment mets z score 1 37 1 07 1 73 conclusion study showed increasing bmi impaired glucose metabolism pose possible risk gallbladder cancer beyond individual factors results also showed metabolic syndrome entity presents risk constellation occurrence gallbladder cancer pubmed","probabilities":0.9799733,"Title":"A prospective study on metabolic risk factors and gallbladder cancer in the metabolic syndrome and cancer (Me-Can) collaborative study","Abstract":"OBJECTIVE: To investigate the association between metabolic risk factors (individually and in combination) and risk of gallbladder cancer (GBC). METHODS: The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden with data on 578,700 men and women. We used Cox proportional hazard regression models to calculate relative risks of GBC by body mass index (BMI), blood pressure, and plasma levels of glucose, cholesterol, and triglycerides as continuous standardised variables and their standardised sum of metabolic syndrome (MetS) z-score. The risk estimates were corrected for random error in measurements. RESULTS: During an average follow-up of 12.0 years (SD = 7.8), 184 primary gallbladder cancers were diagnosed. Relative risk of gallbladder cancer per unit increment of z-score adjusted for age, smoking status and BMI (except for BMI itself) and stratified by birth year, sex and sub-cohorts, was for BMI 1.31 (95% confidence interval 1.11, 1.57) and blood glucose 1.76 (1.10, 2.85). Further analysis showed that the effect of BMI on GBC risk is larger among women in the premenopausal age group (1.84 (1.23, 2.78)) compared to those in the postmenopausal age group (1.29 (0.93, 1.79)). For the other metabolic factors no significant association was found (mid blood pressure 0.96 (0.71, 1.31), cholesterol 0.84 (0.66, 1.06) and serum triglycerides 1.16 (0.82, 1.64)). The relative risk per one unit increment of the MetS z-score was 1.37 (1.07, 1.73). CONCLUSION: This study showed that increasing BMI and impaired glucose metabolism pose a possible risk for gallbladder cancer. Beyond the individual factors, the results also showed that the metabolic syndrome as an entity presents a risk constellation for the occurrence of gallbladder cancer.","Source":"PubMed","category":"HUMAN","training_data":"A prospective study on metabolic risk factors and gallbladder cancer in the metabolic syndrome and cancer (Me-Can) collaborative study OBJECTIVE: To investigate the association between metabolic risk factors (individually and in combination) and risk of gallbladder cancer (GBC). METHODS: The metabolic syndrome and cancer project (Me-Can) includes cohorts from Norway, Austria, and Sweden with data on 578,700 men and women. We used Cox proportional hazard regression models to calculate relative risks of GBC by body mass index (BMI), blood pressure, and plasma levels of glucose, cholesterol, and triglycerides as continuous standardised variables and their standardised sum of metabolic syndrome (MetS) z-score. The risk estimates were corrected for random error in measurements. RESULTS: During an average follow-up of 12.0 years (SD = 7.8), 184 primary gallbladder cancers were diagnosed. Relative risk of gallbladder cancer per unit increment of z-score adjusted for age, smoking status and BMI (except for BMI itself) and stratified by birth year, sex and sub-cohorts, was for BMI 1.31 (95% confidence interval 1.11, 1.57) and blood glucose 1.76 (1.10, 2.85). Further analysis showed that the effect of BMI on GBC risk is larger among women in the premenopausal age group (1.84 (1.23, 2.78)) compared to those in the postmenopausal age group (1.29 (0.93, 1.79)). For the other metabolic factors no significant association was found (mid blood pressure 0.96 (0.71, 1.31), cholesterol 0.84 (0.66, 1.06) and serum triglycerides 1.16 (0.82, 1.64)). The relative risk per one unit increment of the MetS z-score was 1.37 (1.07, 1.73). CONCLUSION: This study showed that increasing BMI and impaired glucose metabolism pose a possible risk for gallbladder cancer. Beyond the individual factors, the results also showed that the metabolic syndrome as an entity presents a risk constellation for the occurrence of gallbladder cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors distal cholangiocarcinoma curative surgery series 84 cases background aims aim study identify useful prognostic factors patients distal cholangiocarcinoma methodology records 84 patients distal cholangiocarcinoma undergoing pancreatoduodenectomy retrospectively reviewed potential clinicopathological prognostic factors may affect survival examined univariate multivariate analyses results two patients died within 30 days surgery overall survival rates 69 51 42 68 36 59 1 3 5 years respectively median survival time 32 74 months univariate analysis found alanine aminotransferase aspartate aminotransferase ast alt ratio less equal 2 serum bilirubin less equal 171 micromol l ca19 9 level less 150 u l tumor size less 2 cm absent neural invasion absent lymph node involvement associated higher survival rate p 0 05 furthermore multivariate analysis found ast alt ratio 2 present lymph node involvement present neural invasion independent risk factors poor survival p 0 01 conclusions results suggest well known lymph node involvement also neural invasion ast alt ratio 2 might useful prognostic factors long term survival distal cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Prognostic factors of distal cholangiocarcinoma after curative surgery: a series of 84 cases","Abstract":"BACKGROUND/AIMS: The aim of this study was to identify useful prognostic factors for patients with distal cholangiocarcinoma. METHODOLOGY: The records of 84 patients with distal cholangiocarcinoma undergoing pancreatoduodenectomy were retrospectively reviewed. Potential clinicopathological prognostic factors that may affect survival were examined by univariate and multivariate analyses. RESULTS: There were two patients died within 30 days of surgery. Overall survival rates were 69.51%, 42.68%, and 36.59% for 1, 3 and 5 years, respectively (median survival time, 32.74 months). Univariate analysis found that alanine aminotransferase/aspartate aminotransferase (AST/ALT) ratio less than and equal to 2, serum bilirubin less than and equal to 171 micromol/L, CA19-9 level less than 150 U/L, tumor size less than 2 cm, absent neural invasion, and absent lymph node involvement were associated with higher survival rate (p < 0.05). Furthermore, multivariate analysis found that AST/ALT ratio more than 2, present lymph node involvement and present neural invasion were the independent risk factors of poor survival (p < 0.01). CONCLUSIONS: These results suggest that not only the well-known lymph node involvement, but also neural invasion and AST/ALT ratio more than 2 might be useful prognostic factors for long-term survival in distal cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors of distal cholangiocarcinoma after curative surgery: a series of 84 cases BACKGROUND/AIMS: The aim of this study was to identify useful prognostic factors for patients with distal cholangiocarcinoma. METHODOLOGY: The records of 84 patients with distal cholangiocarcinoma undergoing pancreatoduodenectomy were retrospectively reviewed. Potential clinicopathological prognostic factors that may affect survival were examined by univariate and multivariate analyses. RESULTS: There were two patients died within 30 days of surgery. Overall survival rates were 69.51%, 42.68%, and 36.59% for 1, 3 and 5 years, respectively (median survival time, 32.74 months). Univariate analysis found that alanine aminotransferase/aspartate aminotransferase (AST/ALT) ratio less than and equal to 2, serum bilirubin less than and equal to 171 micromol/L, CA19-9 level less than 150 U/L, tumor size less than 2 cm, absent neural invasion, and absent lymph node involvement were associated with higher survival rate (p < 0.05). Furthermore, multivariate analysis found that AST/ALT ratio more than 2, present lymph node involvement and present neural invasion were the independent risk factors of poor survival (p < 0.01). CONCLUSIONS: These results suggest that not only the well-known lymph node involvement, but also neural invasion and AST/ALT ratio more than 2 might be useful prognostic factors for long-term survival in distal cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathologic analysis ampullary neoplasms 450 patients implications surgical strategy long term prognosis background whether ampullary neoplasms best surgically managed pancreaticoduodenectomy versus local ampullectomy controversial sought examine outcome patients undergoing pancreaticoduodenectomy versus ampullectomy well identify factors predictive lymph node metastasis patients ampullary neoplasms methods 1970 2007 450 patients underwent surgical resection ampullary adenoma adenocarcinoma identified prospective single institution database data clinicopathologic factors morbidity mortality survival analyzed results initial surgical procedure pancreaticoduodenectomy 96 7 patients ampullectomy 3 3 final diagnosis invasive adenocarcinoma 77 1 adenoma 22 9 median tumor size similar adenomas associated adenocarcinoma 2 5 cm versus adenomas without invasive cancer 2 9 cm p 0 71 morbidity comparable pancreaticoduodenectomy 52 2 versus ampullectomy 33 3 p 0 15 30 day mortality pancreaticoduodenectomy 2 1 versus ampullectomy 0 p 0 6 metastatic disease regional lymph nodes present 54 5 patients adenocarcinoma factors associated presence lymph node metastasis included tumor size 1 cm 2 1 poor histologicgrade 4 8 perineural invasion 3 0 microscopic vessel invasion 6 6 depth invasion pt1 4 3 p 0 05 specifically risk lymph node metastasis increased stage t1 28 0 t2 50 9 t3 71 7 t4 77 3 p 0 001 conclusion surgery indicated radical resection required early invasive adenocarcinoma ampulla vater lymph node metastases present nearly 30 patients t1 disease pancreaticoduodenectomy preferred approach ampullary neoplasms require surgical resection stn","probabilities":0.9799733,"Title":"Clinicopathologic Analysis Of Ampullary Neoplasms In 450 Patients: Implications For Surgical Strategy And Long-Term Prognosis","Abstract":"Background: Whether ampullary neoplasms are best surgically managed by pancreaticoduodenectomy versus local ampullectomy is controversial. We sought to examine the outcome of patients undergoing pancreaticoduodenectomy versus ampullectomy, as well as to identify factors predictive of lymph node metastasis in patients with ampullary neoplasms. \r\n\r\n Methods: Between 1970 and 2007, 450 patients who underwent surgical resection of ampullary adenoma or adenocarcinoma were identified from a prospective, single-institution database. Data on clinicopathologic factors, morbidity, mortality, and survival were analyzed. \r\n\r\n Results: The initial surgical procedure was pancreaticoduodenectomy in 96.7% patients and ampullectomy in 3.3%. Final diagnosis was invasive adenocarcinoma (77.1%) or adenoma (22.9%). Median tumor size was similar for adenomas associated with an adenocarcinoma (2.5 cm) versus adenomas without invasive cancer (2.9 cm; P=0.71). Morbidity was comparable with pancreaticoduodenectomy (52.2%) versus ampullectomy (33.3%; P=0.15), as was 30-day mortality (pancreaticoduodenectomy, 2.1% versus ampullectomy, 0%; P=0.6). Metastatic disease to regional lymph nodes was present in 54.5% patients with adenocarcinoma. Factors associated with presence of lymph node metastasis included tumor size > or = 1 cm (OR 2.1), poor histologicgrade (OR 4.8), perineural invasion (OR 3.0), microscopic vessel invasion (OR 6.6), and depth of invasion > pT1 (OR 4.3; all P<0.05). Specifically, risk of lymph node metastasis increased with T stage (T1, 28.0%; T2, 50.9%; T3, 71.7%; T4, 77.3%; P<0.001). \r\n\r\n Conclusion: When surgery is indicated, radical resection is required for early invasive adenocarcinoma of the ampulla of Vater, as lymph node metastases are present in nearly 30% of patients with T1 disease. Pancreaticoduodenectomy should be the preferred approach for most ampullary neoplasms that require surgical resection.","Source":"STN","category":"HUMAN","training_data":"Clinicopathologic Analysis Of Ampullary Neoplasms In 450 Patients: Implications For Surgical Strategy And Long-Term Prognosis Background: Whether ampullary neoplasms are best surgically managed by pancreaticoduodenectomy versus local ampullectomy is controversial. We sought to examine the outcome of patients undergoing pancreaticoduodenectomy versus ampullectomy, as well as to identify factors predictive of lymph node metastasis in patients with ampullary neoplasms. \r\n\r\n Methods: Between 1970 and 2007, 450 patients who underwent surgical resection of ampullary adenoma or adenocarcinoma were identified from a prospective, single-institution database. Data on clinicopathologic factors, morbidity, mortality, and survival were analyzed. \r\n\r\n Results: The initial surgical procedure was pancreaticoduodenectomy in 96.7% patients and ampullectomy in 3.3%. Final diagnosis was invasive adenocarcinoma (77.1%) or adenoma (22.9%). Median tumor size was similar for adenomas associated with an adenocarcinoma (2.5 cm) versus adenomas without invasive cancer (2.9 cm; P=0.71). Morbidity was comparable with pancreaticoduodenectomy (52.2%) versus ampullectomy (33.3%; P=0.15), as was 30-day mortality (pancreaticoduodenectomy, 2.1% versus ampullectomy, 0%; P=0.6). Metastatic disease to regional lymph nodes was present in 54.5% patients with adenocarcinoma. Factors associated with presence of lymph node metastasis included tumor size > or = 1 cm (OR 2.1), poor histologicgrade (OR 4.8), perineural invasion (OR 3.0), microscopic vessel invasion (OR 6.6), and depth of invasion > pT1 (OR 4.3; all P<0.05). Specifically, risk of lymph node metastasis increased with T stage (T1, 28.0%; T2, 50.9%; T3, 71.7%; T4, 77.3%; P<0.001). \r\n\r\n Conclusion: When surgery is indicated, radical resection is required for early invasive adenocarcinoma of the ampulla of Vater, as lymph node metastases are present in nearly 30% of patients with T1 disease. Pancreaticoduodenectomy should be the preferred approach for most ampullary neoplasms that require surgical resection. STN","prediction_labels":"HUMAN"},{"cleaned":"parenchymal preserving hepatectomy perihilar cholangiocarcinoma background although extended hepatic resection shown improve prognosis increasing surgical curability rate hilar cholangiocarcinoma high surgical morbidity mortality rates reported patients obstructive jaundice postoperative liver failure hepatic resection patients obstructive jaundice shown depend volume resected hepatic mass aim study evaluate results parenchyma preserving hepatectomy surgical treatment hilar cholangiocarcinoma study design ninety three resected patients hilar cholangiocarcinoma included retrospective study resected patients stratified three groups extended hepatectomy exh group n 66 parenchyma preserving hepatectomy pph group n 14 local resection lr group n 13 exh group undergone hepatectomy extensive hemihepatectomy pph group undergone hepatectomy less extensive hemihepatectomy lr group undergone extrahepatic bile duct resection without hepatic resection surgical curability defined histologically confirmed negative surgical margins surgical morbidity mortality survival rates compared among three groups clinicopathologic factors studied prognostic value univariate multivariate analyses results surgical curability pph exh groups better lr group fifty four percent patients lr group showed positive surgical margins hepatic stump bile duct compared 7 pph group 20 exh groups p 0 01 comparison surgical morbidity higher exh group 48 lr group 8 pph group 14 p 0 01 p 0 05 respectively postoperative hyperbilirubinemia occurred frequently exh group 29 lr pph groups 0 0 respectively p 0 05 comparison survival rates resection significantly higher patients underwent hepatectomy including pph exh patients underwent lr 29 versus 8 5 years respectively p 0 05 significant difference survival found pph exh groups univariate multivariate analyses showed significant prognostic factors survival resected margin lymph nodal status vascular resection conclusions conclusion pph obtain curative resection improve outcomes patients hilar cholangiocarcinoma localized hepatic duct confluence require vascular resection pph might bring beneficial effect highly selected patients according extent cancer high risk patients liver dysfunction stn","probabilities":0.9799733,"Title":"Parenchymal Preserving Hepatectomy In Perihilar Cholangiocarcinoma","Abstract":"Background: Although extended hepatic resection has been shown to improve prognosis by increasing the surgical curability rate in hilar cholangiocarcinoma, high surgical morbidity and mortality rates have been reported in patients with obstructive jaundice. Postoperative liver failure after hepatic resection in patients with obstructive jaundice has been shown to depend on the volume of the resected hepatic mass. The aim of this study was to evaluate the results of parenchyma-preserving hepatectomy in a surgical treatment for hilar cholangiocarcinoma. \r\n\r\n Study design: Ninety-three resected patients with hilar cholangiocarcinoma were included in this retrospective study. The resected patients were stratified into three groups: the extended hepatectomy (EXH) group (n = 66), the parenchyma-preserving hepatectomy (PPH) group (n = 14), and the local resection (LR) group (n = 13). The EXH group had undergone hepatectomy more extensive than hemihepatectomy, the PPH group had undergone hepatectomy less extensive than hemihepatectomy, and the LR group had undergone extrahepatic bile duct resection without hepatic resection. Surgical curability, defined by histologically confirmed negative surgical margins, surgical morbidity and mortality, and survival rates were compared among the three groups. The clinicopathologic factors were studied for prognostic value by univariate and multivariate analyses. \r\n\r\n Results: Surgical curability of the PPH and EXH groups was better than that of the LR group. Fifty-four percent of patients in the LR group showed positive surgical margins at the hepatic stump of the bile duct, compared with 7% in the PPH group and 20% in the EXH groups (p < 0.01 for each comparison). Surgical morbidity was higher in the EXH group (48%) than in the LR group (8%) and the PPH group (14%) (p < 0.01 and p < 0.05, respectively). Postoperative hyperbilirubinemia occurred more frequently in the EXH group (29%) than in the LR and PPH groups (0% and 0%, respectively, p < 0.05 for each comparison). Survival rates after resection were significantly higher in patients who underwent hepatectomy, including PPH and EXH, than in patients who underwent LR, 29% versus 8% at 5 years, respectively (p < 0.05). But no significant difference in survival was found between the PPH and EXH groups. Univariate and multivariate analyses showed that significant prognostic factors for survival were resected margin, lymph nodal status, and vascular resection. \r\n\r\n Conclusions: In conclusion, PPH could obtain a curative resection and improve the outcomes for patients with hilar cholangiocarcinoma that is localized at the hepatic duct confluence who do not require vascular resection. PPH might bring about a beneficial effect in highly selected patients according to extent of cancer and high-risk patients with liver dysfunction.","Source":"STN","category":"HUMAN","training_data":"Parenchymal Preserving Hepatectomy In Perihilar Cholangiocarcinoma Background: Although extended hepatic resection has been shown to improve prognosis by increasing the surgical curability rate in hilar cholangiocarcinoma, high surgical morbidity and mortality rates have been reported in patients with obstructive jaundice. Postoperative liver failure after hepatic resection in patients with obstructive jaundice has been shown to depend on the volume of the resected hepatic mass. The aim of this study was to evaluate the results of parenchyma-preserving hepatectomy in a surgical treatment for hilar cholangiocarcinoma. \r\n\r\n Study design: Ninety-three resected patients with hilar cholangiocarcinoma were included in this retrospective study. The resected patients were stratified into three groups: the extended hepatectomy (EXH) group (n = 66), the parenchyma-preserving hepatectomy (PPH) group (n = 14), and the local resection (LR) group (n = 13). The EXH group had undergone hepatectomy more extensive than hemihepatectomy, the PPH group had undergone hepatectomy less extensive than hemihepatectomy, and the LR group had undergone extrahepatic bile duct resection without hepatic resection. Surgical curability, defined by histologically confirmed negative surgical margins, surgical morbidity and mortality, and survival rates were compared among the three groups. The clinicopathologic factors were studied for prognostic value by univariate and multivariate analyses. \r\n\r\n Results: Surgical curability of the PPH and EXH groups was better than that of the LR group. Fifty-four percent of patients in the LR group showed positive surgical margins at the hepatic stump of the bile duct, compared with 7% in the PPH group and 20% in the EXH groups (p < 0.01 for each comparison). Surgical morbidity was higher in the EXH group (48%) than in the LR group (8%) and the PPH group (14%) (p < 0.01 and p < 0.05, respectively). Postoperative hyperbilirubinemia occurred more frequently in the EXH group (29%) than in the LR and PPH groups (0% and 0%, respectively, p < 0.05 for each comparison). Survival rates after resection were significantly higher in patients who underwent hepatectomy, including PPH and EXH, than in patients who underwent LR, 29% versus 8% at 5 years, respectively (p < 0.05). But no significant difference in survival was found between the PPH and EXH groups. Univariate and multivariate analyses showed that significant prognostic factors for survival were resected margin, lymph nodal status, and vascular resection. \r\n\r\n Conclusions: In conclusion, PPH could obtain a curative resection and improve the outcomes for patients with hilar cholangiocarcinoma that is localized at the hepatic duct confluence who do not require vascular resection. PPH might bring about a beneficial effect in highly selected patients according to extent of cancer and high-risk patients with liver dysfunction. STN","prediction_labels":"HUMAN"},{"cleaned":"clinical prognostic factors genomic alterations cholangiocarcinoma thai population study explores genomic alterations cholangiocarcinoma ccc tissues thai patients identified reviewed records patients diagnosed ccc sufficient tumor samples dna rna extraction available database specimens explored egfr kras braf pik3ca mutations ros1 translocation 81 samples immunohistochemistry staining her2 alk ki 67 expression tested 74 samples prevalence egfr kras pik3ca mutations study 21 12 16 respectively braf v600 mutation ros1 translocation found patients t790m mutation significantly longer overall survival 18 84 months types egfr mutations 4 08 months hazard ratio hr 0 26 p 0 038 also significantly lower median ki 67 22 5 vs 80 p 0 025 furthermore patients pik3ca mutations significantly longer median progression free survival 15 87 vs 7 01 months hr 0 46 p 0 043 strongly positive her2 expression found 1 patient whereas alk expression found presence egfr pik3ca mutations implies targeted drugs may provide feasible ccc treatment future stn","probabilities":0.9285714,"Title":"Clinical Prognostic Factors And Genomic Alterations Of Cholangiocarcinoma In Thai Population","Abstract":"This study explores genomic alterations in cholangiocarcinoma (CCC) tissues in Thai patients. We identified and reviewed the records of patients who had been diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA extraction were available in our database. The specimens were explored for EGFR, KRAS, BRAF, and PIK3CA mutations and ROS1 translocation in 81 samples. Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in 74 samples. Prevalence of EGFR, KRAS, and PIK3CA mutations in this study was 21%, 12%, and 16%, respectively. No BRAF V600 mutation or ROS1 translocation was found. Patients with T790M mutation had a significantly longer overall survival (18.84 months) than those with the other types of EGFR mutations (4.08 months; hazard ratio [HR]: 0.26, P=0.038) and also had a significantly lower median Ki-67 (22.5% vs 80%, P=0.025). Furthermore, patients with PIK3CA mutations had a significantly longer median progression-free survival (15.87 vs 7.01 months; HR: 0.46, P=0.043). Strongly positive HER2 expression was found in only 1 patient, whereas ALK expression was not found. The presence of EGFR and/or PIK3CA mutations implies that targeted drugs may provide a feasible CCC treatment in the future.","Source":"STN","category":"ANIMAL","training_data":"Clinical Prognostic Factors And Genomic Alterations Of Cholangiocarcinoma In Thai Population This study explores genomic alterations in cholangiocarcinoma (CCC) tissues in Thai patients. We identified and reviewed the records of patients who had been diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA extraction were available in our database. The specimens were explored for EGFR, KRAS, BRAF, and PIK3CA mutations and ROS1 translocation in 81 samples. Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in 74 samples. Prevalence of EGFR, KRAS, and PIK3CA mutations in this study was 21%, 12%, and 16%, respectively. No BRAF V600 mutation or ROS1 translocation was found. Patients with T790M mutation had a significantly longer overall survival (18.84 months) than those with the other types of EGFR mutations (4.08 months; hazard ratio [HR]: 0.26, P=0.038) and also had a significantly lower median Ki-67 (22.5% vs 80%, P=0.025). Furthermore, patients with PIK3CA mutations had a significantly longer median progression-free survival (15.87 vs 7.01 months; HR: 0.46, P=0.043). Strongly positive HER2 expression was found in only 1 patient, whereas ALK expression was not found. The presence of EGFR and/or PIK3CA mutations implies that targeted drugs may provide a feasible CCC treatment in the future. STN","prediction_labels":"ANIMAL"},{"cleaned":"differentiation benign malignant ampullary obstruction multi row detector ct purpose determine useful ct parameters differentiate ampullary carcinomas benign ampullary obstruction materials methods study included 93 patients underwent abdominal ct 31 patients ampullary carcinomas 62 patients benign ampullary obstruction two radiologists independently evaluated ct parameters reached consensus decisions statistically significant ct parameters identified univariate multivariate analyses results univariate analysis presence ampullary mass asymmetric abrupt narrowing distal common bile duct cbd dilated intrahepatic bile duct ihd dilated pancreatic duct pd peripancreatic lymphadenopathy duodenal wall thickening delayed enhancement frequently ampullary carcinomas observed p 0 05 multivariate logistic regression analysis using significant ct parameters clinical data univariate analysis clinical symptom jaundice p 0 005 independent predictor ampullary carcinomas multivariate analysis using significant ct parameters abrupt narrowing distal cbd independent predictor ampullary carcinomas p 0 019 among various ct criteria abrupt narrowing distal cbd dilated ihd highest sensitivity 77 4 highest accuracy 90 3 conclusion abrupt narrowing distal cbd dilated ihd useful differentiation ampullary carcinomas benign entity patients without presence mass stn","probabilities":0.9799733,"Title":"Differentiation Of Benign And Malignant Ampullary Obstruction By Multi-Row Detector Ct","Abstract":"Purpose: To determine useful CT parameters to differentiate ampullary carcinomas from benign ampullary obstruction. \n\n Materials and methods: This study included 93 patients who underwent abdominal CT, 31 patients with ampullary carcinomas, and 62 patients with benign ampullary obstruction. Two radiologists independently evaluated CT parameters then reached consensus decisions. Statistically significant CT parameters were identified through univariate and multivariate analyses. \n\n Results: In univariate analysis, the presence of ampullary mass, asymmetric, abrupt narrowing of distal common bile duct (CBD), dilated intrahepatic bile duct (IHD), dilated pancreatic duct (PD), peripancreatic lymphadenopathy, duodenal wall thickening, and delayed enhancement were more frequently in ampullary carcinomas observed (P < 0.05). Multivariate logistic regression analysis using significant CT parameters and clinical data from univariate analysis, and clinical symptom with jaundice (P = 0.005) was an independent predictor of ampullary carcinomas. For multivariate analysis using only significant CT parameters, abrupt narrowing of distal CBD was an independent predictor of ampullary carcinomas (P = 0.019). Among various CT criteria, abrupt narrowing of distal CBD and dilated IHD had highest sensitivity (77.4%) and highest accuracy (90.3%). \n\n Conclusion: The abrupt narrowing of distal CBD and dilated IHD is useful for differentiation of ampullary carcinomas from benign entity in patients without the presence of mass.","Source":"STN","category":"HUMAN","training_data":"Differentiation Of Benign And Malignant Ampullary Obstruction By Multi-Row Detector Ct Purpose: To determine useful CT parameters to differentiate ampullary carcinomas from benign ampullary obstruction. \n\n Materials and methods: This study included 93 patients who underwent abdominal CT, 31 patients with ampullary carcinomas, and 62 patients with benign ampullary obstruction. Two radiologists independently evaluated CT parameters then reached consensus decisions. Statistically significant CT parameters were identified through univariate and multivariate analyses. \n\n Results: In univariate analysis, the presence of ampullary mass, asymmetric, abrupt narrowing of distal common bile duct (CBD), dilated intrahepatic bile duct (IHD), dilated pancreatic duct (PD), peripancreatic lymphadenopathy, duodenal wall thickening, and delayed enhancement were more frequently in ampullary carcinomas observed (P < 0.05). Multivariate logistic regression analysis using significant CT parameters and clinical data from univariate analysis, and clinical symptom with jaundice (P = 0.005) was an independent predictor of ampullary carcinomas. For multivariate analysis using only significant CT parameters, abrupt narrowing of distal CBD was an independent predictor of ampullary carcinomas (P = 0.019). Among various CT criteria, abrupt narrowing of distal CBD and dilated IHD had highest sensitivity (77.4%) and highest accuracy (90.3%). \n\n Conclusion: The abrupt narrowing of distal CBD and dilated IHD is useful for differentiation of ampullary carcinomas from benign entity in patients without the presence of mass. STN","prediction_labels":"HUMAN"},{"cleaned":"transarterial chemoembolization versus supportive therapy palliative treatment unresectable intrahepatic cholangiocarcinoma aim evaluate clinical outcome survival benefits transarterial chemoembolization tace unresectable intrahepatic cholangiocarcinoma icc compared supportive therapy materials methods january 1996 april 2009 total 155 patients unresectable icc met entry criteria underwent tace 72 patients supportive treatment 83 patients survival primary end point results baseline patients tumour characteristics well balanced two groups median number sessions per patient 2 5 range 1 17 sessions tace group tace incidence significant grade 3 haematological non haematological toxicities 13 24 respectively patients died within 30 days following tace objective tumour regression partial response achieved 23 patients tace group kaplan meier survival analysis showed survival period significantly longer tace group median 12 2 months symptomatic treatment median 3 3 months group p 0 001 conclusions tace safe offers greater survival benefits supportive treatment palliative treatment unresectable icc stn","probabilities":0.9799733,"Title":"Transarterial Chemoembolization Versus Supportive Therapy In The Palliative Treatment Of Unresectable Intrahepatic Cholangiocarcinoma","Abstract":"Aim: To evaluate the clinical outcome and the survival benefits of transarterial chemoembolization (TACE) for unresectable intrahepatic cholangiocarcinoma (ICC) compared with supportive therapy. \n\n Materials and methods: From January 1996 to April 2009, a total of 155 patients with unresectable ICC met the entry criteria and underwent TACE (72 patients) or supportive treatment (83 patients). Their survival was the primary end point. \n\n Results: The baseline patients and tumour characteristics were well-balanced in the two groups. The median number of sessions per patient was 2.5 (range 1-17 sessions) in the TACE group. After TACE, the incidence of significant (≥ grade 3) haematological and non-haematological toxicities was 13 and 24%, respectively, and no patients died within 30 days following TACE. The objective tumour regression (≥ partial response) was achieved in 23% of the patients in the TACE group. The Kaplan-Meier survival analysis showed that the survival period was significantly longer in the TACE group (median 12.2 months) than in the symptomatic treatment (median 3.3 months) group (p < 0.001). \n\n Conclusions: TACE is safe and offers greater survival benefits than supportive treatment for the palliative treatment of unresectable ICC.","Source":"STN","category":"HUMAN","training_data":"Transarterial Chemoembolization Versus Supportive Therapy In The Palliative Treatment Of Unresectable Intrahepatic Cholangiocarcinoma Aim: To evaluate the clinical outcome and the survival benefits of transarterial chemoembolization (TACE) for unresectable intrahepatic cholangiocarcinoma (ICC) compared with supportive therapy. \n\n Materials and methods: From January 1996 to April 2009, a total of 155 patients with unresectable ICC met the entry criteria and underwent TACE (72 patients) or supportive treatment (83 patients). Their survival was the primary end point. \n\n Results: The baseline patients and tumour characteristics were well-balanced in the two groups. The median number of sessions per patient was 2.5 (range 1-17 sessions) in the TACE group. After TACE, the incidence of significant (≥ grade 3) haematological and non-haematological toxicities was 13 and 24%, respectively, and no patients died within 30 days following TACE. The objective tumour regression (≥ partial response) was achieved in 23% of the patients in the TACE group. The Kaplan-Meier survival analysis showed that the survival period was significantly longer in the TACE group (median 12.2 months) than in the symptomatic treatment (median 3.3 months) group (p < 0.001). \n\n Conclusions: TACE is safe and offers greater survival benefits than supportive treatment for the palliative treatment of unresectable ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"serum adhesion molecule 1 icam 1 potential prognostic marker cholangiocarcinoma patients cholangiocarcinoma cca malignancy bile ducts high incidence invasion metastasis disease often detected advanced stages difficulties early diagnosis leading high mortality rate however biomarkers early cca detection still lacking study identify potential biomarker proteins differential secretome analysis gelc ms ms approach applied four cca cell lines control immortalized cholangiocyte cell line among 78 regulated proteins 53 including icam 1 exclusively expressed four cca secretomes mmnk1 based result measured icam 1 levels serum samples cca patients healthy controls found significantly higher values cca patients sera receiver operating characteristic curve analysis suggested serum icam 1 level discriminatory diagnostic marker cca healthy controls area curve 0 829 sensitivity 77 specificity 70 cut value 167 ng ml moreover serum icam 1 showed positive correlations alkaline phosphatase carcinoembryonic antigen levels comparison icam 1 levels paired pre post operative sera 12 cases revealed significant decrease tumor resection however serum icam 1 levels significantly different cca benign biliary diseases mainly inflammatory features stn","probabilities":0.9467213,"Title":"Serum Adhesion Molecule-1 (Icam-1) As A Potential Prognostic Marker For Cholangiocarcinoma Patients","Abstract":"Cholangiocarcinoma (CCA) is a malignancy of bile ducts with a high incidence of invasion and metastasis. This disease is often detected in advanced stages because of the difficulties of early diagnosis, leading to a high mortality rate. However, biomarkers for early CCA detection are still lacking. In this study, to identify potential biomarker proteins, differential secretome analysis by the GeLC-MS/MS approach was applied with four CCA cell lines and a control immortalized cholangiocyte cell line. Among 78 up-regulated proteins, 53 including ICAM- 1 were exclusively expressed in four CCA secretomes but not in MMNK1. Based on this result, we measured ICAM-1 levels in serum samples of CCA patients and healthy controls and found significantly higher values in CCA patients' sera. Receiver operating characteristic curve analysis suggested that serum ICAM-1 level could be a discriminatory diagnostic marker for CCA and healthy controls (area under curve=0.829) with a sensitivity of 77% and a specificity of 70% at a cut off value of 167 ng/ml. Moreover, the serum ICAM-1 showed positive correlations with alkaline phosphatase and carcinoembryonic antigen levels. Comparison of ICAM-1 levels of paired pre- and post-operative sera of 12 cases revealed significant decrease after tumor resection. However, serum ICAM-1 levels were not significantly different between CCA and benign biliary diseases with mainly inflammatory features.","Source":"STN","category":"ANIMAL","training_data":"Serum Adhesion Molecule-1 (Icam-1) As A Potential Prognostic Marker For Cholangiocarcinoma Patients Cholangiocarcinoma (CCA) is a malignancy of bile ducts with a high incidence of invasion and metastasis. This disease is often detected in advanced stages because of the difficulties of early diagnosis, leading to a high mortality rate. However, biomarkers for early CCA detection are still lacking. In this study, to identify potential biomarker proteins, differential secretome analysis by the GeLC-MS/MS approach was applied with four CCA cell lines and a control immortalized cholangiocyte cell line. Among 78 up-regulated proteins, 53 including ICAM- 1 were exclusively expressed in four CCA secretomes but not in MMNK1. Based on this result, we measured ICAM-1 levels in serum samples of CCA patients and healthy controls and found significantly higher values in CCA patients' sera. Receiver operating characteristic curve analysis suggested that serum ICAM-1 level could be a discriminatory diagnostic marker for CCA and healthy controls (area under curve=0.829) with a sensitivity of 77% and a specificity of 70% at a cut off value of 167 ng/ml. Moreover, the serum ICAM-1 showed positive correlations with alkaline phosphatase and carcinoembryonic antigen levels. Comparison of ICAM-1 levels of paired pre- and post-operative sera of 12 cases revealed significant decrease after tumor resection. However, serum ICAM-1 levels were not significantly different between CCA and benign biliary diseases with mainly inflammatory features. STN","prediction_labels":"ANIMAL"},{"cleaned":"gemcitabine plus cisplatin chemotherapy patients biliary tract cancer evidence suggests combined gemcitabine cisplatin chemotherapy extends survival patients advanced biliary tract cancer btc conducted systematic review order collate evidence assess whether gemcitabine cisplatin efficacy influenced primary tumor site disease stage geographic region whether associated toxicities related regimen medline 1946 search date embase 1966 search date clinicaltrials gov 2008 search date abstracts major oncology conferences 2009 search date searched 5 dec 2013 using terms btc gemcitabine cisplatin study types reporting efficacy survival response rates safety toxicities outcomes gemcitabine cisplatin btc eligible inclusion efficacy data extracted prospective studies evidence retrieved one meta analysis abstract four randomized controlled trials 12 nonrandomized prospective studies three retrospective studies supported efficacy safety gemcitabine cisplatin btc median overall survival ranged 4 6 11 7 months response rate ranged 17 1 36 6 toxicities generally acceptable manageable heterogeneity study designs data collected prevented formal meta analysis however exploratory assessments suggested efficacy vary primary tumor site gallbladder vs others disease stage metastatic vs locally advanced geographic origin asia vs incidence grade 3 4 toxicities related gemcitabine dose cisplatin frequency despite individual variation study designs evidence presented suggests gemcitabine cisplatin effective patients diverse range countries heterogeneous disease characteristics substantial differences toxicity observed among different dosing schedules gemcitabine cisplatin google scholar","probabilities":0.9799733,"Title":"Gemcitabine Plus Cisplatin Chemotherapy For Patients With Biliary Tract Cancer","Abstract":"Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends survival in patients with advanced biliary tract cancer (BTC). We conducted a systematic review in order to collate this evidence and assess whether gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease stage, or geographic region, and whether associated toxicities are related to regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials. gov (2008-search date), and abstracts from major oncology conferences (2009- search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and cisplatin. All study types reporting efficacy (survival, response rates) or safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for inclusion; efficacy data were extracted from prospective studies only. Evidence retrieved from one meta-analysis (abstract), four randomized controlled trials, 12 nonrandomized prospective studies, and three retrospective studies supported the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable. Heterogeneity in study designs and data collected prevented formal meta-analysis, however exploratory assessments suggested that efficacy did not vary with primary tumor site (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency. Despite individual variation in study designs, the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics. No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin.","Source":"Google Scholar","category":"HUMAN","training_data":"Gemcitabine Plus Cisplatin Chemotherapy For Patients With Biliary Tract Cancer Evidence suggests that combined gemcitabine-cisplatin chemotherapy extends survival in patients with advanced biliary tract cancer (BTC). We conducted a systematic review in order to collate this evidence and assess whether gemcitabine-cisplatin efficacy is influenced by primary tumor site, disease stage, or geographic region, and whether associated toxicities are related to regimen. MEDLINE (1946-search date), EMBASE (1966-search date), ClinicalTrials. gov (2008-search date), and abstracts from major oncology conferences (2009- search date) were searched (5 Dec 2013) using terms for BTC, gemcitabine, and cisplatin. All study types reporting efficacy (survival, response rates) or safety (toxicities) outcomes of gemcitabine-cisplatin in BTC were eligible for inclusion; efficacy data were extracted from prospective studies only. Evidence retrieved from one meta-analysis (abstract), four randomized controlled trials, 12 nonrandomized prospective studies, and three retrospective studies supported the efficacy and safety of gemcitabine-cisplatin for BTC. Median overall survival ranged from 4.6 to 11.7 months, and response rate ranged from 17.1% to 36.6%. Toxicities were generally acceptable and manageable. Heterogeneity in study designs and data collected prevented formal meta-analysis, however exploratory assessments suggested that efficacy did not vary with primary tumor site (gallbladder vs. others), disease stage (metastatic vs. locally advanced), or geographic origin (Asia vs. other). Incidence of grade 3/4 toxicities was not related to gemcitabine dose or cisplatin frequency. Despite individual variation in study designs, the evidence presented suggests that gemcitabine-cisplatin is effective in patients from a diverse range of countries and with heterogeneous disease characteristics. No substantial differences in toxicity were observed among the different dosing schedules of gemcitabine and cisplatin. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"programmed death ligand 1 expression correlation clinicopathological parameters gallbladder cancer background immunomodulatory therapies targeting interaction programmed cell death protein 1 programmed death ligand 1 pd l1 become increasingly important anticancer treatment previous research subject immune response established association tumor aggressiveness poor prognosis certain cancers currently scant information available relationship pd l1 expression gallbladder cancer gbc methods investigated expression pd l1 101 primary gbc cases determine potential association prognostic impact pd l1 expression immunohistochemically assessed using single pd l1 antibody clone sp263 correlations clinicopathological parameters overall survival os progression free survival pfs analyzed results pd l1 expression tumor cells cutoff levels 1 10 50 present 18 8 13 8 7 9 cases study showed positive pd l1 expression cutoff significantly correlated poorly differentiated histologic grade presence lymphovascular invasion p 05 pd l1 expression cutoff levels 10 50 significantly positive patients perineural invasion higher categories higher pathologic stages p 05 additionally significant association noted pd l1 expression cutoff level 50 worse os pfs p 049 os p 028 pfs poor prognostic factors included histologic grade category n category pathologic stage lymphovascular invasion perineural invasion growth pattern margin resection p 05 conclusions expression pd l1 gbc varies according cutoff level valuably associated poor prognostic parameters survival study indicates overexpression pd l1 gbc negative prognostic impact google scholar","probabilities":0.54545456,"Title":"Programmed Death-Ligand 1 Expression And Its Correlation With Clinicopathological Parameters In Gallbladder Cancer","Abstract":"Background\nImmunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC).\nMethods\nWe investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression- free survival (PFS) were analyzed.\nResults\nPD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05).\nConclusions\nThe expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact.","Source":"Google Scholar","category":"HUMAN","training_data":"Programmed Death-Ligand 1 Expression And Its Correlation With Clinicopathological Parameters In Gallbladder Cancer Background\nImmunomodulatory therapies targeting the interaction between programmed cell death protein 1 and programmed death-ligand 1 (PD-L1) have become increasingly important in anticancer treatment. Previous research on the subject of this immune response has established an association with tumor aggressiveness and a poor prognosis in certain cancers. Currently, scant information is available on the relationship between PD-L1 expression and gallbladder cancer (GBC).\nMethods\nWe investigated the expression of PD-L1 in 101 primary GBC cases to determine the potential association with prognostic impact. PD-L1 expression was immunohistochemically assessed using a single PD-L1 antibody (clone SP263). Correlations with clinicopathological parameters, overall survival (OS), or progression- free survival (PFS) were analyzed.\nResults\nPD-L1 expression in tumor cells at cutoff levels of 1%, 10%, and 50% was present in 18.8%, 13.8%, and 7.9% of cases. Our study showed that positive PD-L1 expression at any cutoff was significantly correlated with poorly differentiated histologic grade and the presence of lymphovascular invasion (p < .05). PD-L1 expression at cutoff levels of 10% and 50% was significantly positive in patients with perineural invasion, higher T categories, and higher pathologic stages (p < .05). Additionally, there was a significant association noted between PD-L1 expression at a cutoff level of 50% and worse OS or PFS (p = .049 for OS, p = .028 for PFS). Other poor prognostic factors included histologic grade, T category, N category, pathologic stage, lymphovascular invasion, perineural invasion, growth pattern, and margin of resection (p < .05).\nConclusions\nThe expression of PD-L1 in GBC varies according to cutoff level but is valuably associated with poor prognostic parameters and survival. Our study indicates that the overexpression of PD-L1 in GBC had a negative prognostic impact. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"diagnostic prognostic value immunohistochemical expression s100p imp3 transpapillary biliary forceps biopsy samples extrahepatic bile duct carcinoma background biopsy specimen extrahepatic bile duct carcinoma ehbdc small shows reactive changes histological distinction malignant benign tissue difficult recent studies reported s100p insulin like growth factor ii mrna binding protein 3 imp3 diagnostic molecules also prognostic biomarkers several organs objective study clarify diagnostic prognostic value immunohistochemical expression s100p imp3 transpapillary biliary forceps biopsy tbfb samples methods tbfb samples collected 80 patients ehbdc 68 patients benign 12 patients retrospectively results using cytoplasmic positive staining imp3 marker malignancy sensitivity specificity reached 79 4 91 7 respectively sensitivity specificity accuracy achieved 89 7 91 7 90 0 respectively using positive staining imp3 positive histology maker malignancy univariate p 0 033 multivariate p 0 039 analysis revealed s100p positive ehbdc patients showed significantly shorter survival conclusions results study suggest immunohistochemical staining imp3 useful diagnosis ehbdc s100p useful prognostic marker ehbdc pubmed","probabilities":0.7966102,"Title":"Diagnostic and prognostic value of immunohistochemical expression of S100P and IMP3 in transpapillary biliary forceps biopsy samples of extrahepatic bile duct carcinoma","Abstract":"BACKGROUND: Because the biopsy specimen of extrahepatic bile duct carcinoma (EHBDC) is small and shows reactive changes, the histological distinction between malignant and benign tissue can be difficult. Recent studies reported that S100P and insulin-like growth factor II mRNA-binding protein 3 (IMP3) were not only diagnostic molecules but also prognostic biomarkers in several organs. The objective of this study is to clarify the diagnostic and prognostic value of immunohistochemical expression of S100P and IMP3 in transpapillary biliary forceps biopsy (TBFB) samples. METHODS: The TBFB samples were collected from 80 patients (EHBDC, 68 patients; benign, 12 patients), retrospectively. RESULTS: When using cytoplasmic-positive staining for IMP3 as a marker of malignancy, the sensitivity and specificity reached 79.4 and 91.7 %, respectively. The sensitivity, specificity and accuracy achieved 89.7, 91.7 and 90.0 %, respectively, when using positive staining for IMP3 and/or positive histology as a maker of malignancy. While univariate (P = 0.033) and multivariate (P = 0.039) analysis revealed that S100P-positive EHBDC patients showed significantly shorter survival. CONCLUSIONS: The results of this study suggest that immunohistochemical staining for IMP3 is useful in the diagnosis of EHBDC and that of S100P is useful as a prognostic marker for EHBDC.","Source":"PubMed","category":"ANIMAL","training_data":"Diagnostic and prognostic value of immunohistochemical expression of S100P and IMP3 in transpapillary biliary forceps biopsy samples of extrahepatic bile duct carcinoma BACKGROUND: Because the biopsy specimen of extrahepatic bile duct carcinoma (EHBDC) is small and shows reactive changes, the histological distinction between malignant and benign tissue can be difficult. Recent studies reported that S100P and insulin-like growth factor II mRNA-binding protein 3 (IMP3) were not only diagnostic molecules but also prognostic biomarkers in several organs. The objective of this study is to clarify the diagnostic and prognostic value of immunohistochemical expression of S100P and IMP3 in transpapillary biliary forceps biopsy (TBFB) samples. METHODS: The TBFB samples were collected from 80 patients (EHBDC, 68 patients; benign, 12 patients), retrospectively. RESULTS: When using cytoplasmic-positive staining for IMP3 as a marker of malignancy, the sensitivity and specificity reached 79.4 and 91.7 %, respectively. The sensitivity, specificity and accuracy achieved 89.7, 91.7 and 90.0 %, respectively, when using positive staining for IMP3 and/or positive histology as a maker of malignancy. While univariate (P = 0.033) and multivariate (P = 0.039) analysis revealed that S100P-positive EHBDC patients showed significantly shorter survival. CONCLUSIONS: The results of this study suggest that immunohistochemical staining for IMP3 is useful in the diagnosis of EHBDC and that of S100P is useful as a prognostic marker for EHBDC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"exposure 12 dichloropropane upregulates expression activation induced cytidine deaminase aid human cholangiocytes co cultured macrophages 1 2 dichloropropane 1 2 dcp reclassified recently iarc group 1 carcinogen based epidemiological studies outbreak cholangiocarcinoma offset printing workers exposed 1 2 dcp japan however underlying mechanism 1 2 dcp induced cholangiocarcinoma remains obscure previous whole genome mutation analysis cholangiocarcinoma 4 cases exposed 1 2 dcp suggested involvement activation induced cytidine deaminase aid based specific signatures mutation patterns objective present study determine whether exposure 1 2 dcp induces expression aid human cholangiocytes human mmnk 1 cholangiocytes differentiated thp 1 macrophages co cultures mmnk 1 thp 1 cells exposed 1 2 dcp different concentrations time intervals mrna expression levels aid related genes quantified real time pcr protein expression measured immunostaining alkaline comet assay performed examine dna damage results showed 1 2 dcp alone change aid expression mmnk 1 cholangiocytes 1 2 dcp significantly increased pro inflammatory cytokine tnf expression thp 1 macrophages tnf treatment upregulated expression aid nf b b mmnk 1 cholangiocytes sn50 nf b inhibitor significantly downregulated tnf induced aid expression suggesting involvement nf b pathway tnf induced aid expression exposure 1 2 dcp significantly increased aid expression mmnk 1 cholangiocytes co cultured thp 1 macrophages comet assay showed 1 2 dcp induced dna damage mmnk 1 cholangiocytes indicated increased tail dna tail moment enhanced co cultured macrophages results suggest inflammatory response macrophages consequent aberrant aid expression dna damage cholangiocytes underlie mechanism 1 2 dcp induced cholangiocarcinoma humans stn","probabilities":1.0,"Title":"Exposure To 12-Dichloropropane Upregulates The Expression Of Activation-Induced Cytidine Deaminase (Aid) In Human Cholangiocytes Co-Cultured With Macrophages","Abstract":"1,2-dichloropropane (1,2-DCP) was reclassified recently by IARC as a Group 1 carcinogen based on epidemiological studies on an outbreak of cholangiocarcinoma in offset-printing workers exposed to 1,2-DCP in Japan. However, the underlying mechanism of 1,2-DCP-induced cholangiocarcinoma remains obscure. A previous whole-genome mutation analysis of cholangiocarcinoma of 4 cases exposed to 1,2-DCP suggested the involvement of activation-induced cytidine deaminase (AID), based on specific signatures of mutation patterns. The objective of the present study is to determine whether exposure to 1,2-DCP induces expression of AID in human cholangiocytes. Human MMNK-1 cholangiocytes, differentiated THP-1 macrophages, and co-cultures of MMNK-1/THP-1 cells were exposed to 1,2-DCP at different concentrations and time intervals. The mRNA expression levels of AID and related genes were quantified by real-time PCR. Protein expression was measured by immunostaining. Alkaline Comet assay was performed to examine DNA damage. The results showed that 1,2-DCP alone did not change AID expression in MMNK-1 cholangiocytes. 1,2-DCP significantly increased pro-inflammatory cytokine TNF-α expression in THP-1 macrophages. TNF-α treatment upregulated expression of AID, NF-κB, and IκB in MMNK-1 cholangiocytes. SN50, a NF-κB inhibitor, significantly downregulated TNF-α-induced AID expression, suggesting the involvement of NF-κB pathway in TNF-α-induced AID expression. Exposure to 1,2-DCP significantly increased AID expression in MMNK-1 cholangiocytes co-cultured with THP-1 macrophages. Comet assay showed that 1,2-DCP-induced DNA damage in MMNK-1 cholangiocytes, as indicated by increased tail DNA% and tail moment, was enhanced when co-cultured with macrophages. The results suggest that inflammatory response of macrophages and consequent aberrant AID expression or DNA damage in the cholangiocytes underlie the mechanism of 1,2-DCP-induced cholangiocarcinoma in humans.","Source":"STN","category":"ANIMAL","training_data":"Exposure To 12-Dichloropropane Upregulates The Expression Of Activation-Induced Cytidine Deaminase (Aid) In Human Cholangiocytes Co-Cultured With Macrophages 1,2-dichloropropane (1,2-DCP) was reclassified recently by IARC as a Group 1 carcinogen based on epidemiological studies on an outbreak of cholangiocarcinoma in offset-printing workers exposed to 1,2-DCP in Japan. However, the underlying mechanism of 1,2-DCP-induced cholangiocarcinoma remains obscure. A previous whole-genome mutation analysis of cholangiocarcinoma of 4 cases exposed to 1,2-DCP suggested the involvement of activation-induced cytidine deaminase (AID), based on specific signatures of mutation patterns. The objective of the present study is to determine whether exposure to 1,2-DCP induces expression of AID in human cholangiocytes. Human MMNK-1 cholangiocytes, differentiated THP-1 macrophages, and co-cultures of MMNK-1/THP-1 cells were exposed to 1,2-DCP at different concentrations and time intervals. The mRNA expression levels of AID and related genes were quantified by real-time PCR. Protein expression was measured by immunostaining. Alkaline Comet assay was performed to examine DNA damage. The results showed that 1,2-DCP alone did not change AID expression in MMNK-1 cholangiocytes. 1,2-DCP significantly increased pro-inflammatory cytokine TNF-α expression in THP-1 macrophages. TNF-α treatment upregulated expression of AID, NF-κB, and IκB in MMNK-1 cholangiocytes. SN50, a NF-κB inhibitor, significantly downregulated TNF-α-induced AID expression, suggesting the involvement of NF-κB pathway in TNF-α-induced AID expression. Exposure to 1,2-DCP significantly increased AID expression in MMNK-1 cholangiocytes co-cultured with THP-1 macrophages. Comet assay showed that 1,2-DCP-induced DNA damage in MMNK-1 cholangiocytes, as indicated by increased tail DNA% and tail moment, was enhanced when co-cultured with macrophages. The results suggest that inflammatory response of macrophages and consequent aberrant AID expression or DNA damage in the cholangiocytes underlie the mechanism of 1,2-DCP-induced cholangiocarcinoma in humans. STN","prediction_labels":"ANIMAL"},{"cleaned":"dendritic cell based immunotherapy targeting synthesized peptides advanced biliary tract cancer background aim retrospective study clarify safety efficacy dendritic cell dc based immunotherapy targeting synthesized peptides wilms tumor 1 wt1 mucin 1 cell surface associated muc1 biliary tract cancers btcs methods sixty five patients nonresectable recurrent metastatic btcs received dc based immunotherapy selected study dcs pulsed wt1 muc1 adverse events aes clinical responses examined results serious treatment related aes observed median survival time mst diagnosis first vaccination 18 5 7 2 months respectively multivariate cox proportional hazard analysis significant independent factors found 1 combined chemotherapy 2 albumin level 4 0 g dl vaccination 3 c reactive protein level 0 5 mg dl vaccination 4 fever vaccination mst first vaccination without chemotherapy 8 2 5 3 months respectively p 0 016 mst patients prognostic nutritional index 40 40 8 1 5 0 months respectively p 0 023 conclusions although small uncontrolled nonrandomized study dc based immunotherapy btcs safe produced clinical response patients underwent chemotherapy maintained good nutrition status pubmed","probabilities":0.962963,"Title":"Dendritic cell-based immunotherapy targeting synthesized peptides for advanced biliary tract cancer","Abstract":"BACKGROUND: The aim of this retrospective study was to clarify the safety and efficacy of dendritic cell (DC)-based immunotherapy targeting synthesized peptides, Wilms tumor 1 (WT1) and Mucin 1, cell surface associated (MUC1) for biliary tract cancers (BTCs). METHODS: Sixty-five patients who had nonresectable, recurrent, or metastatic BTCs and received the DC-based immunotherapy were selected for the study. DCs were pulsed with WT1 and/or MUC1. The adverse events (AEs) and clinical responses were examined. RESULTS: No serious treatment-related AEs were observed. Median survival time (MST) from diagnosis and from the first vaccination was 18.5 and 7.2 months, respectively. By multivariate Cox proportional hazard analysis, the significant independent factors were found to be (1) combined chemotherapy, (2) albumin level ≥4.0 g/dL before vaccination, (3) C-reactive protein level <0.5 mg/dL before vaccination, and (4) fever after vaccination. The MST from the first vaccination with or without chemotherapy was 8.2 and 5.3 months, respectively (P = 0.016), and MST for the patients with prognostic nutritional index ≥40 and <40 was 8.1 and 5.0 months, respectively (P = 0.023). CONCLUSIONS: Although a small uncontrolled nonrandomized study, DC-based immunotherapy for BTCs was safe and produced a clinical response for the patients who underwent chemotherapy and maintained a good nutrition status.","Source":"PubMed","category":"HUMAN","training_data":"Dendritic cell-based immunotherapy targeting synthesized peptides for advanced biliary tract cancer BACKGROUND: The aim of this retrospective study was to clarify the safety and efficacy of dendritic cell (DC)-based immunotherapy targeting synthesized peptides, Wilms tumor 1 (WT1) and Mucin 1, cell surface associated (MUC1) for biliary tract cancers (BTCs). METHODS: Sixty-five patients who had nonresectable, recurrent, or metastatic BTCs and received the DC-based immunotherapy were selected for the study. DCs were pulsed with WT1 and/or MUC1. The adverse events (AEs) and clinical responses were examined. RESULTS: No serious treatment-related AEs were observed. Median survival time (MST) from diagnosis and from the first vaccination was 18.5 and 7.2 months, respectively. By multivariate Cox proportional hazard analysis, the significant independent factors were found to be (1) combined chemotherapy, (2) albumin level ≥4.0 g/dL before vaccination, (3) C-reactive protein level <0.5 mg/dL before vaccination, and (4) fever after vaccination. The MST from the first vaccination with or without chemotherapy was 8.2 and 5.3 months, respectively (P = 0.016), and MST for the patients with prognostic nutritional index ≥40 and <40 was 8.1 and 5.0 months, respectively (P = 0.023). CONCLUSIONS: Although a small uncontrolled nonrandomized study, DC-based immunotherapy for BTCs was safe and produced a clinical response for the patients who underwent chemotherapy and maintained a good nutrition status. PubMed","prediction_labels":"HUMAN"},{"cleaned":"dysregulated yap1 taz tgf signaling mediate hepatocarcinogenesis mob1a 1b deficient mice mps one binder kinase activator mob 1a 1b core components hippo pathway coactivate large tumor suppressor homolog lats kinases mob1a 1b double deficiency mouse liver lmob1dko results hyperplasia oval cells immature cholangiocytes accompanied inflammatory cell infiltration fibrosis half mutant mice die within 3 wk birth survivors eventually develop liver cancers particularly combined hepatocellular cholangiocarcinomas chc ccs intrahepatic cholangiocellular carcinomas iccs die age 60 wk phenotype severe among mutant mice lacking hippo signaling component mob1a 1b constitute critical hub hippo signaling mammalian liver lmob1dko liver cells show hyperproliferation increased cell saturation density hepatocyte dedifferentiation enhanced epithelial mesenchymal transition cell migration elevated transforming growth factor beta tgf 2 3 production changes strongly dependent yes associated protein 1 yap1 partially dependent pdz binding motif taz tgfbr2 independent connective tissue growth factor ctgf human liver cancers yap1 activation frequent chc ccs iccs correlates smad family member 2 activation drug screening revealed antiparasitic macrocyclic lactones inhibit yap1 activation vitro vivo targeting yap1 taz drugs combination inhibition tgf pathway may effective treatment chc ccs iccs stn","probabilities":0.9467213,"Title":"Dysregulated Yap1/Taz And Tgf-ß Signaling Mediate Hepatocarcinogenesis In Mob1A/1B-Deficient Mice","Abstract":"Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway that coactivate large tumor suppressor homolog (LATS) kinases. Mob1a/1b double deficiency in mouse liver (LMob1DKO) results in hyperplasia of oval cells and immature cholangiocytes accompanied by inflammatory cell infiltration and fibrosis. More than half of mutant mice die within 3 wk of birth. All survivors eventually develop liver cancers, particularly combined hepatocellular and cholangiocarcinomas (cHC-CCs) and intrahepatic cholangiocellular carcinomas (ICCs), and die by age 60 wk. Because this phenotype is the most severe among mutant mice lacking a Hippo signaling component, MOB1A/1B constitute the critical hub of Hippo signaling in mammalian liver. LMob1DKO liver cells show hyperproliferation, increased cell saturation density, hepatocyte dedifferentiation, enhanced epithelial-mesenchymal transition and cell migration, and elevated transforming growth factor beta(TGF-β)2/3 production. These changes are strongly dependent on Yes-Associated Protein-1 (Yap1) and partially dependent on PDZ-binding motif (Taz) and Tgfbr2, but independent of connective tissue growth factor (Ctgf). In human liver cancers, YAP1 activation is frequent in cHC-CCs and ICCs and correlates with SMAD family member 2 activation. Drug screening revealed that antiparasitic macrocyclic lactones inhibit YAP1 activation in vitro and in vivo. Targeting YAP1/TAZ with these drugs in combination with inhibition of the TGF-β pathway may be effective treatment for cHC-CCs and ICCs.","Source":"STN","category":"ANIMAL","training_data":"Dysregulated Yap1/Taz And Tgf-ß Signaling Mediate Hepatocarcinogenesis In Mob1A/1B-Deficient Mice Mps One Binder Kinase Activator (MOB)1A/1B are core components of the Hippo pathway that coactivate large tumor suppressor homolog (LATS) kinases. Mob1a/1b double deficiency in mouse liver (LMob1DKO) results in hyperplasia of oval cells and immature cholangiocytes accompanied by inflammatory cell infiltration and fibrosis. More than half of mutant mice die within 3 wk of birth. All survivors eventually develop liver cancers, particularly combined hepatocellular and cholangiocarcinomas (cHC-CCs) and intrahepatic cholangiocellular carcinomas (ICCs), and die by age 60 wk. Because this phenotype is the most severe among mutant mice lacking a Hippo signaling component, MOB1A/1B constitute the critical hub of Hippo signaling in mammalian liver. LMob1DKO liver cells show hyperproliferation, increased cell saturation density, hepatocyte dedifferentiation, enhanced epithelial-mesenchymal transition and cell migration, and elevated transforming growth factor beta(TGF-β)2/3 production. These changes are strongly dependent on Yes-Associated Protein-1 (Yap1) and partially dependent on PDZ-binding motif (Taz) and Tgfbr2, but independent of connective tissue growth factor (Ctgf). In human liver cancers, YAP1 activation is frequent in cHC-CCs and ICCs and correlates with SMAD family member 2 activation. Drug screening revealed that antiparasitic macrocyclic lactones inhibit YAP1 activation in vitro and in vivo. Targeting YAP1/TAZ with these drugs in combination with inhibition of the TGF-β pathway may be effective treatment for cHC-CCs and ICCs. STN","prediction_labels":"ANIMAL"},{"cleaned":"expression n acetylglucosaminyltransferase v subserosal layer correlates postsurgical survival pathological tumor stage 2 carcinoma gallbladder background n acetylglucosaminyltransferase v gnt v enzyme catalyzes 1 6 branching n acetylglucosamine asparagine linked oligosaccharides cellular proteins enhances malignant behaviors carcinoma cells experimental models aim study determine clinical significance gnt v expression human pt2 gallbladder carcinoma simple vitro experiments methods ninety patients pt2 gallbladder carcinoma included study vitro vivo biological effects gnt v investigated using gallbladder carcinoma cells variable gnt v expression levels induced small interfering rna results 90 cases 57 showed positive staining remaining 33 demonstrated negative staining subcellular localization 57 cases classified granular type 31 cases diffuse type 26 cases 76 cases curative resection postsurgical survival significantly poorer showing positive staining showing negative staining p 0 028 76 cases postsurgical recurrence significantly frequent showing diffuse type localization showing negative staining experimental analyses demonstrated regulation gnt v expression gallbladder carcinoma cells induced suppression cell growth vitro expression levels gnt v cells highly correlated rapid vivo growth coupled enhanced angiogenesis tendency form liver metastasis conclusions gnt v expression subserosal layer pt2 gallbladder carcinoma correlated aggressiveness disease stn","probabilities":0.9467213,"Title":"Expression Of N-Acetylglucosaminyltransferase V In The Subserosal Layer Correlates With Postsurgical Survival Of Pathological Tumor Stage 2 Carcinoma Of The Gallbladder","Abstract":"Background: N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the β1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT2 gallbladder carcinoma with simple in vitro experiments. \r\n\r\n Methods: Ninety patients with pT2 gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA. \r\n\r\n Results: Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis. \r\n\r\n Conclusions: GnT-V expression in the subserosal layer of pT2 gallbladder carcinoma is correlated with the aggressiveness of the disease.","Source":"STN","category":"ANIMAL","training_data":"Expression Of N-Acetylglucosaminyltransferase V In The Subserosal Layer Correlates With Postsurgical Survival Of Pathological Tumor Stage 2 Carcinoma Of The Gallbladder Background: N-Acetylglucosaminyltransferase V (GnT-V), an enzyme that catalyzes the β1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cellular proteins, enhances the malignant behaviors of carcinoma cells in experimental models. The aim of this study was to determine clinical significance of GnT-V expression in human pT2 gallbladder carcinoma with simple in vitro experiments. \r\n\r\n Methods: Ninety patients with pT2 gallbladder carcinoma were included for this study. The in vitro and in vivo biological effects of GnT-V were investigated using gallbladder carcinoma cells with variable GnT-V expression levels induced by a small interfering RNA. \r\n\r\n Results: Of the 90 cases, 57 showed positive staining and the remaining 33 demonstrated negative staining, the subcellular localization in the 57 cases was classified into the granular-type in 31 cases and the diffuse-type in 26 cases. In 76 cases with curative resection, postsurgical survival was significantly poorer in those showing positive staining than in those showing negative staining (P = 0.028). In all of the 76 cases, postsurgical recurrence was significantly more frequent in those showing diffuse-type localization than in those showing negative staining. Experimental analyses demonstrated that the down-regulation of GnT-V expression in gallbladder carcinoma cells induced suppression of cell growth in vitro. The expression levels of GnT-V in the cells were highly correlated with the rapid in vivo growth coupled with the enhanced angiogenesis, and the tendency to form liver metastasis. \r\n\r\n Conclusions: GnT-V expression in the subserosal layer of pT2 gallbladder carcinoma is correlated with the aggressiveness of the disease. STN","prediction_labels":"ANIMAL"},{"cleaned":"effect pathologic residual disease curative reresection incidental gallbladder cancer objectives patients diagnosed incidental gallbladder cancer gc benefit optimal extent surgery remain unclear aims study analyse outcomes patients underwent liver resection following diagnosis incidental gc determine factors associated longterm survival methods retrospective analysis patients diagnosed incidental gc june 1999 june 2010 performed data covering demographics clinical surgical characteristics local pathological stage analysed results total 24 patients identified patients underwent resection segments ivb v lymphadenectomy histological examination revealed residual disease 10 patients presented recurrent disease 3 12 months overall 5 year survival 53 increasing stage p 0 001 tumour node metastasis tnm stage p 0 003 presence residual tumour resected liver p 0 001 associated worse survival conclusions aggressive re resection incidental gc offers chance cure efficacy depends extent disease found time repeat surgery presence residual disease correlated strongly stage relevant prognostic factor survival patients treated curative resection stn","probabilities":0.9799733,"Title":"Effect Of Pathologic Residual Disease After Curative Reresection For Incidental Gallbladder Cancer","Abstract":"Objectives: In patients diagnosed with incidental gallbladder cancer (GC), the benefit and optimal extent of further surgery remain unclear. The aims of this study were to analyse outcomes in patients who underwent liver resection following a diagnosis of incidental GC and to determine factors associated with longterm survival. \r\n\r\n Methods: A retrospective analysis of patients diagnosed with incidental GC between June 1999 and June 2010 was performed. Data covering demographics, clinical and surgical characteristics and local pathological stage were analysed. \r\n\r\n Results: A total of 24 patients were identified. All patients underwent a resection of segments IVb and V and lymphadenectomy. Histological examination revealed residual disease in 10 patients, all of whom presented with recurrent disease at 3-12 months. Overall 5-year survival was 53%. Increasing T-stage (P < 0.001), tumour-node-metastasis (TNM) stage (P= 0.003), and the presence of residual tumour in the resected liver (P < 0.001) were all associated with worse survival. \r\n\r\n Conclusions: Aggressive re-resection of incidental GC offers the only chance for cure, but its efficacy depends on the extent of disease found at the time of repeat surgery. The presence of residual disease correlated strongly with T-stage and was the most relevant prognostic factor for survival in patients treated with curative resection.","Source":"STN","category":"HUMAN","training_data":"Effect Of Pathologic Residual Disease After Curative Reresection For Incidental Gallbladder Cancer Objectives: In patients diagnosed with incidental gallbladder cancer (GC), the benefit and optimal extent of further surgery remain unclear. The aims of this study were to analyse outcomes in patients who underwent liver resection following a diagnosis of incidental GC and to determine factors associated with longterm survival. \r\n\r\n Methods: A retrospective analysis of patients diagnosed with incidental GC between June 1999 and June 2010 was performed. Data covering demographics, clinical and surgical characteristics and local pathological stage were analysed. \r\n\r\n Results: A total of 24 patients were identified. All patients underwent a resection of segments IVb and V and lymphadenectomy. Histological examination revealed residual disease in 10 patients, all of whom presented with recurrent disease at 3-12 months. Overall 5-year survival was 53%. Increasing T-stage (P < 0.001), tumour-node-metastasis (TNM) stage (P= 0.003), and the presence of residual tumour in the resected liver (P < 0.001) were all associated with worse survival. \r\n\r\n Conclusions: Aggressive re-resection of incidental GC offers the only chance for cure, but its efficacy depends on the extent of disease found at the time of repeat surgery. The presence of residual disease correlated strongly with T-stage and was the most relevant prognostic factor for survival in patients treated with curative resection. STN","prediction_labels":"HUMAN"},{"cleaned":"f box wd repeat domain containing 7 fbxw7 mrna outcome biliary tract cancer background thestandard treatment biliary tract cancer gemcitabine plus platinum median progression free survival pfs 5 8 months m valle et al nejm 2010 gene expression somatic mutations may influence clinical phenotype affect decisions individualized treatment methods retrospectively analyzed tissue blocks 54 advanced metastatic cholangiocarcinoma gallbladder ampulllary cancer patients p treated single agent gemcitabine gemcitabine plus carboplatin cisplatin using rt pcr analyzed mrna expression levels oncogenes tumor suppressors dna repair genes brca1 rrm1 aeg 1 rap80 spink1 fbxw7 correlated results pfs overall survival os response addition fbxw7 hotspot mutations assessed results p characteristics 72 females median age 60 40 87 fbxw7 expression correlated pfs os fbxw7 levels dichotomized median value pfs 4 2 m p low levels vs 12 6 m p high levels p 0 02 fbxw7 expression divided terciles pfs 4 9 m p lowest tercile 7 6 p intermediate tercile 26 9 m p highest tercile p 0 08 os 6 2 m p lowest tercile 8 m p intermediate tercile reached p highest tercile significant correlation observed expression levels genes examined pfs os aeg 1 expression correlated response p 0 05 fbxw7 hotspot mutations detected conclusions although find fbxw7 hotspot mutations previously described biliary tract cancer fbxw7 mrna expression significantly influenced pfs os separate cohort p analyzed validate prognostic role fbxw7 google scholar","probabilities":0.875,"Title":"F-Box And Wd Repeat Domain-Containing 7 (Fbxw7) Mrna And Outcome In Biliary Tract Cancer","Abstract":"Background: Thestandard treatment for biliary tract cancer is gemcitabine plus platinum, but median progression-free survival (PFS) is only 5-8 months (m) (Valle et al, NEJM 2010). Gene expression or somatic mutations may influence the clinical phenotype, which will affect decisions on individualized treatment. Methods: We retrospectively analyzed tissue blocks from 54 advanced or metastatic cholangiocarcinoma, gallbladder or ampulllary cancer patients (p) treated with single-agent gemcitabine or gemcitabine plus carboplatin or cisplatin. Using RT-PCR, we analyzed the mRNA expression levels of oncogenes, tumor suppressors and DNA repair genes (BRCA1, RRM1, AEG-1, RAP80, SPINK1 and FBXW7) and correlated results with PFS, overall survival (OS) and response. In addition, FBXW7 hotspot mutations were assessed. Results: p characteristics: 72% females; median age, 60 (40-87). Only FBXW7 expression correlated with PFS and OS. When FBXW7 levels were dichotomized at the median value, PFS was 4.2 m for p with low levels vs 12.6 m for p with high levels (p=0.02). When FBXW7 expression was divided by terciles, PFS was 4.9 m for p in the lowest tercile, 7.6 for p in the intermediate tercile, and 26.9 m for p in the highest tercile (p=0.08). OS was 6.2 m for p in the lowest tercile, 8 m for p in the intermediate tercile, and not reached for p in the highest tercile. No other significant correlation was observed between expression levels of the other genes examined and PFS or OS. Only AEG-1 expression correlated with response (p=0.05). No FBXW7 hotspot mutations were detected. Conclusions: Although we did not find the FBXW7 hotspot mutations previously described in biliary tract cancer, FBXW7 mRNA expression significantly influenced PFS and OS. A separate cohort of p is being analyzed to validate the prognostic role of FBXW7.","Source":"Google Scholar","category":"HUMAN","training_data":"F-Box And Wd Repeat Domain-Containing 7 (Fbxw7) Mrna And Outcome In Biliary Tract Cancer Background: Thestandard treatment for biliary tract cancer is gemcitabine plus platinum, but median progression-free survival (PFS) is only 5-8 months (m) (Valle et al, NEJM 2010). Gene expression or somatic mutations may influence the clinical phenotype, which will affect decisions on individualized treatment. Methods: We retrospectively analyzed tissue blocks from 54 advanced or metastatic cholangiocarcinoma, gallbladder or ampulllary cancer patients (p) treated with single-agent gemcitabine or gemcitabine plus carboplatin or cisplatin. Using RT-PCR, we analyzed the mRNA expression levels of oncogenes, tumor suppressors and DNA repair genes (BRCA1, RRM1, AEG-1, RAP80, SPINK1 and FBXW7) and correlated results with PFS, overall survival (OS) and response. In addition, FBXW7 hotspot mutations were assessed. Results: p characteristics: 72% females; median age, 60 (40-87). Only FBXW7 expression correlated with PFS and OS. When FBXW7 levels were dichotomized at the median value, PFS was 4.2 m for p with low levels vs 12.6 m for p with high levels (p=0.02). When FBXW7 expression was divided by terciles, PFS was 4.9 m for p in the lowest tercile, 7.6 for p in the intermediate tercile, and 26.9 m for p in the highest tercile (p=0.08). OS was 6.2 m for p in the lowest tercile, 8 m for p in the intermediate tercile, and not reached for p in the highest tercile. No other significant correlation was observed between expression levels of the other genes examined and PFS or OS. Only AEG-1 expression correlated with response (p=0.05). No FBXW7 hotspot mutations were detected. Conclusions: Although we did not find the FBXW7 hotspot mutations previously described in biliary tract cancer, FBXW7 mRNA expression significantly influenced PFS and OS. A separate cohort of p is being analyzed to validate the prognostic role of FBXW7. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"upregulation agr2vh facilitates cholangiocarcinoma cell survival endoplasmic reticulum stress via activation unfolded protein response pathway cholangiocarcinoma cca epithelial cell malignancy arising within biliary tree liver cca usually diagnosed advanced stage subsequent developing metastasis recently anterior gradient 2 agr2 characterized one highly upregulated genes among metastasis associated genes highly metastatic cca cell lines previous reports demonstrated agr2 required triggering unfolded protein response upr pathway support cancer cell survival particularly endoplasmic reticulum er stress conditions previous study identified agr2 short isoform generated aberrant splicing agr2vh contributed metastatic phenotype cca cells aim present study determine function agr2vh upr pathway activation support cancer cell survivability apoptosis evasion subsequent experimentally inducing er stress agr2vh overexpressing cca cells using tunicamycin upr pathway activated upregulation upr marker genes activating transcription factor 6 eukaryotic initiation factor 2a spliced x box binding protein 1 upr proteins binding immunoglobulin protein glucose regulated protein grp 78 kda phosphorylated eukaryotic translation initiation factor 2a upr downstream targets grp94 addition results verified agr2vh knockdown using specific small interfering rnas er stress conditions overexpression agr2vh reduced number apoptotic cells decreasing caspase 3 7 activity downregulating c ebp homologous protein mrna b cell lymphoma 2 bcl 2 associated x protein expression whereas bcl 2 protein upregulated resulting higher number viable cells results present study support previous data indicate oncogenic agr2vh isoform may promote metastasis associated phenotypes also cca cell survival apoptosis evasion thereby favoring cancer progression stn","probabilities":0.9467213,"Title":"Upregulation Of Agr2Vh Facilitates Cholangiocarcinoma Cell Survival Under Endoplasmic Reticulum Stress Via The Activation Of The Unfolded Protein Response Pathway","Abstract":"Cholangiocarcinoma (CCA) is an epithelial cell malignancy arising within the biliary tree in the liver. CCA is usually diagnosed at an advanced stage, subsequent to developing with metastasis. Recently, anterior gradient‑2 (AGR2) was characterized as one of the most highly upregulated genes among all metastasis‑associated genes in highly metastatic CCA cell lines. Previous reports have demonstrated that AGR2 is required for triggering the unfolded protein response (UPR) pathway to support cancer cell survival, particularly under endoplasmic reticulum (ER) stress conditions. A previous study identified an AGR2 short isoform generated by aberrant splicing, AGR2vH, which contributed to the metastatic phenotype of CCA cells. The aim of the present study was to determine the function of AGR2vH in UPR pathway activation to support cancer cell survivability and apoptosis evasion. Subsequent to experimentally inducing ER stress in AGR2vH‑overexpressing CCA cells using tunicamycin, the UPR pathway was activated by the upregulation of UPR marker genes (activating transcription factor 6, eukaryotic initiation factor 2a and spliced X‑box binding protein 1), UPR proteins [binding immunoglobulin protein/glucose‑regulated protein (GRP)78 kDa and phosphorylated eukaryotic translation initiation factor 2a] and UPR downstream targets (GRP94). In addition, the results were verified by AGR2vH knockdown using specific small interfering RNAs. Under ER stress conditions, the overexpression of AGR2vH reduced the number of apoptotic cells by decreasing caspase‑3/7 activity and downregulating C/EBP homologous protein mRNA and B‑cell lymphoma‑2 (Bcl‑2)‑associated X protein expression, whereas the Bcl‑2 protein was upregulated, resulting in a higher number of viable cells. The results of the present study support the previous data that indicate that an oncogenic AGR2vH isoform may not only promote metastasis‑associated phenotypes, but also CCA cell survival and apoptosis evasion, thereby favoring cancer progression.","Source":"STN","category":"ANIMAL","training_data":"Upregulation Of Agr2Vh Facilitates Cholangiocarcinoma Cell Survival Under Endoplasmic Reticulum Stress Via The Activation Of The Unfolded Protein Response Pathway Cholangiocarcinoma (CCA) is an epithelial cell malignancy arising within the biliary tree in the liver. CCA is usually diagnosed at an advanced stage, subsequent to developing with metastasis. Recently, anterior gradient‑2 (AGR2) was characterized as one of the most highly upregulated genes among all metastasis‑associated genes in highly metastatic CCA cell lines. Previous reports have demonstrated that AGR2 is required for triggering the unfolded protein response (UPR) pathway to support cancer cell survival, particularly under endoplasmic reticulum (ER) stress conditions. A previous study identified an AGR2 short isoform generated by aberrant splicing, AGR2vH, which contributed to the metastatic phenotype of CCA cells. The aim of the present study was to determine the function of AGR2vH in UPR pathway activation to support cancer cell survivability and apoptosis evasion. Subsequent to experimentally inducing ER stress in AGR2vH‑overexpressing CCA cells using tunicamycin, the UPR pathway was activated by the upregulation of UPR marker genes (activating transcription factor 6, eukaryotic initiation factor 2a and spliced X‑box binding protein 1), UPR proteins [binding immunoglobulin protein/glucose‑regulated protein (GRP)78 kDa and phosphorylated eukaryotic translation initiation factor 2a] and UPR downstream targets (GRP94). In addition, the results were verified by AGR2vH knockdown using specific small interfering RNAs. Under ER stress conditions, the overexpression of AGR2vH reduced the number of apoptotic cells by decreasing caspase‑3/7 activity and downregulating C/EBP homologous protein mRNA and B‑cell lymphoma‑2 (Bcl‑2)‑associated X protein expression, whereas the Bcl‑2 protein was upregulated, resulting in a higher number of viable cells. The results of the present study support the previous data that indicate that an oncogenic AGR2vH isoform may not only promote metastasis‑associated phenotypes, but also CCA cell survival and apoptosis evasion, thereby favoring cancer progression. STN","prediction_labels":"ANIMAL"},{"cleaned":"trends survival patients diagnosed cancer digestive organs nordic countries 1964 2003 followed end 2006 cancers digestive organs including oesophagus stomach small intestine colon rectum anus liver gallbladder pancreas constitute one fifth cancer cases nordic countries group diseases diverse time trends varying consequences public health study examine trends relative survival relation corresponding incidence mortality rates nordic countries period 1964 2003 material methods data retrieved nordcan database period 1964 2003 grouped eight 5 year periods diagnosis patients followed end 2006 analysis comprised trends 5 year relative survival excess mortality age specific relative survival results survival following cancers colon rectum increased continuously observed period yet danish patients fall behind nordic countries largest inter country variation seen rare cancers small intestine little increase prognosis patients diagnosed cancers liver gallbladder pancreas 5 year survival generally 15 survival also remains consistently low patients oesophageal cancer minor increases survival seen among stomach cancer patients countries except denmark concomitant incidence mortality rates stomach cancer steadily decreased nordic country least since 1964 conclusion site specific variations mortality survival largely reflect extent changing improving diagnostic clinical practices incidence trends highlight importance risk factor modification alongside ongoing clinical advances effective primary prevention measures including control alcohol tobacco consumption well changing dietary pattern reduce incidence mortality burden digestive cancers nordic countries pubmed","probabilities":0.9799733,"Title":"Trends in survival of patients diagnosed with cancer of the digestive organs in the Nordic countries 1964-2003 followed up to the end of 2006","Abstract":"Cancers of the digestive organs (including the oesophagus, stomach, small intestine, colon, rectum and anus, liver, gallbladder, and pancreas) constitute one-fifth of all cancer cases in the Nordic countries and is a group of diseases with diverse time trends and varying consequences for public health. In this study we examine trends in relative survival in relation to the corresponding incidence and mortality rates in the Nordic countries during the period 1964-2003. MATERIAL AND METHODS: Data were retrieved from the NORDCAN database for the period 1964 to 2003, grouped into eight 5-year periods of diagnosis. The patients were followed up until the end of 2006. Analysis comprised trends in 5-year relative survival, excess mortality and age-specific relative survival. RESULTS: Survival following cancers of the colon and rectum has increased continuously over the observed period, yet Danish patients fall behind those in the other Nordic countries. The largest inter-country variation is seen for the rare cancers in the small intestine. There has been little increase in prognosis for patients diagnosed with cancers of the liver, gallbladder or pancreas; 5-year survival is generally below 15%. Survival also remains consistently low for patients with oesophageal cancer, while minor increases in survival are seen among stomach cancer patients in all countries except Denmark. The concomitant incidence and mortality rates of stomach cancer have steadily decreased in each Nordic country at least since 1964. CONCLUSION: While the site-specific variations in mortality and survival largely reflect the extent of changing and improving diagnostic and clinical practices, the incidence trends highlight the importance of risk factor modification. Alongside the ongoing clinical advances, effective primary prevention measures, including the control of alcohol and tobacco consumption as well as changing dietary pattern, will reduce the incidence and mortality burden of digestive cancers in the Nordic countries.","Source":"PubMed","category":"HUMAN","training_data":"Trends in survival of patients diagnosed with cancer of the digestive organs in the Nordic countries 1964-2003 followed up to the end of 2006 Cancers of the digestive organs (including the oesophagus, stomach, small intestine, colon, rectum and anus, liver, gallbladder, and pancreas) constitute one-fifth of all cancer cases in the Nordic countries and is a group of diseases with diverse time trends and varying consequences for public health. In this study we examine trends in relative survival in relation to the corresponding incidence and mortality rates in the Nordic countries during the period 1964-2003. MATERIAL AND METHODS: Data were retrieved from the NORDCAN database for the period 1964 to 2003, grouped into eight 5-year periods of diagnosis. The patients were followed up until the end of 2006. Analysis comprised trends in 5-year relative survival, excess mortality and age-specific relative survival. RESULTS: Survival following cancers of the colon and rectum has increased continuously over the observed period, yet Danish patients fall behind those in the other Nordic countries. The largest inter-country variation is seen for the rare cancers in the small intestine. There has been little increase in prognosis for patients diagnosed with cancers of the liver, gallbladder or pancreas; 5-year survival is generally below 15%. Survival also remains consistently low for patients with oesophageal cancer, while minor increases in survival are seen among stomach cancer patients in all countries except Denmark. The concomitant incidence and mortality rates of stomach cancer have steadily decreased in each Nordic country at least since 1964. CONCLUSION: While the site-specific variations in mortality and survival largely reflect the extent of changing and improving diagnostic and clinical practices, the incidence trends highlight the importance of risk factor modification. Alongside the ongoing clinical advances, effective primary prevention measures, including the control of alcohol and tobacco consumption as well as changing dietary pattern, will reduce the incidence and mortality burden of digestive cancers in the Nordic countries. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment options primary sclerosing cholangitis primary sclerosing cholangitis cholestatic liver disease characterized inflammation fibrosis intra extrahepatic bile ducts leading multifocal strictures primary sclerosing cholangitis exhibits progressive course resulting cirrhosis need liver transplantation median period 12 years disease frequently associated inflammatory bowel disease carries increased risk colorectal cancer cholangiocarcinoma despite extensive research currently effective medical treatment multiple drugs shown ineffective halting disease progression including ursodeoxycholic acid widely evaluated drug high dose ursodeoxycholic acid 28 30 mg kg day recently shown increase adverse events rate endoscopic radiological dilatation dominant stricture may lead symptomatic biochemical improvement however liver transplantation life prolonging treatment patients end stage disease studies promising drugs antibiotics antifibrotic agents bile acid derivatives eagerly awaited pubmed","probabilities":0.9799733,"Title":"Treatment options for primary sclerosing cholangitis","Abstract":"Primary sclerosing cholangitis is a cholestatic liver disease characterized by inflammation and fibrosis of intra-/extrahepatic bile ducts, leading to multifocal strictures. Primary sclerosing cholangitis exhibits a progressive course resulting in cirrhosis and the need for liver transplantation over a median period of 12 years. The disease is frequently associated with inflammatory bowel disease and carries an increased risk of colorectal cancer and cholangiocarcinoma. Despite extensive research, there is currently no effective medical treatment. Multiple drugs are shown to be ineffective in halting disease progression, including ursodeoxycholic acid, the most widely evaluated drug. High-dose ursodeoxycholic acid (28-30 mg/kg/day) was recently shown to increase the adverse events rate. Endoscopic or radiological dilatation of a 'dominant' stricture may lead to symptomatic and biochemical improvement. However, liver transplantation is the only life-prolonging treatment for patients with end-stage disease. Studies with promising drugs, such as antibiotics, antifibrotic agents and bile acid derivatives, are eagerly awaited.","Source":"PubMed","category":"HUMAN","training_data":"Treatment options for primary sclerosing cholangitis Primary sclerosing cholangitis is a cholestatic liver disease characterized by inflammation and fibrosis of intra-/extrahepatic bile ducts, leading to multifocal strictures. Primary sclerosing cholangitis exhibits a progressive course resulting in cirrhosis and the need for liver transplantation over a median period of 12 years. The disease is frequently associated with inflammatory bowel disease and carries an increased risk of colorectal cancer and cholangiocarcinoma. Despite extensive research, there is currently no effective medical treatment. Multiple drugs are shown to be ineffective in halting disease progression, including ursodeoxycholic acid, the most widely evaluated drug. High-dose ursodeoxycholic acid (28-30 mg/kg/day) was recently shown to increase the adverse events rate. Endoscopic or radiological dilatation of a 'dominant' stricture may lead to symptomatic and biochemical improvement. However, liver transplantation is the only life-prolonging treatment for patients with end-stage disease. Studies with promising drugs, such as antibiotics, antifibrotic agents and bile acid derivatives, are eagerly awaited. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hhla2 intrahepatic cholangiocarcinoma immune checkpoint prognostic significance wider expression compared pd l1 background intrahepatic cholangiocarcinoma icc highly mortal malignancy limited therapeutic options immunotherapies targeting pd 1 pd l1 pathway represent promising treatment icc however pd l1 expression microsatellite instability common icc study aimed investigate whether hhla2 newly identified b7 family immune checkpoint cells therapeutic target next pd l1 icc methods expression levels pd l1 hhla2 well infiltrations cd3 cd8 cd4 foxp3 cd68 cd163 cd20 cells evaluated immunohistochemistry 153 resected icc samples comprehensive comparisons made pd l1 hhla2 terms expression rates clinicopathological features infiltrations different immune cells expression level prognostic significance hhla2 validated independent cohort results expression hhla2 frequent pd l1 icc 49 0 vs 28 1 co expression immune checkpoints infrequent 13 1 50 pd l1 negative cases elevated hhla2 hhla2 overexpression associated sparser cd3 tumor infiltrating lymphocytes tils cd8 tils higher cd4 foxp3 cd8 til ratio whereas pd l1 expression associated prominent cells cd163 tumor associated macrophages infiltrations pd l1 failed stratify overall survival os hhla2 identified independent prognostic indicator os two independent cohorts conclusions compared pd l1 hhla2 prevalent possesses explicit prognostic significance confer rationale hhla2 potential immunotherapeutic target next pd l1 icc patients stn","probabilities":0.9799733,"Title":"Hhla2 In Intrahepatic Cholangiocarcinoma: An Immune Checkpoint With Prognostic Significance And Wider Expression Compared With Pd-L1","Abstract":"Background: Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. This study aimed to investigate whether HHLA2, a newly identified B7 family immune checkpoint for T cells, could be a therapeutic target next to PD-L1 in ICC. \r\n\r\n Methods: Expression levels of PD-L1 and HHLA2 as well as infiltrations of CD3+, CD8+, CD4 + Foxp3+, CD68+, CD163+ and CD20+ cells were evaluated by immunohistochemistry in 153 resected ICC samples. Comprehensive comparisons were made between PD-L1 and HHLA2 in terms of the expression rates, clinicopathological features and infiltrations of different immune cells. The expression level and prognostic significance of HHLA2 were further validated in an independent cohort. \r\n\r\n Results: Expression of HHLA2 is more frequent than PD-L1 in ICC (49.0% vs 28.1%). Co-expression of both immune checkpoints was infrequent (13.1%) and 50% PD-L1 negative cases were with elevated HHLA2. HHLA2 overexpression was associated with sparser CD3+ tumor infiltrating lymphocytes (TILs), CD8+ TILs and a higher CD4 + Foxp3+/CD8+ TIL ratio, whereas PD-L1 expression was associated with prominent T cells and CD163+ tumor associated macrophages infiltrations. PD-L1 failed to stratify overall survival (OS) but HHLA2 was identified as an independent prognostic indicator for OS in two independent cohorts. \r\n\r\n Conclusions: Compared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients.","Source":"STN","category":"ANIMAL","training_data":"Hhla2 In Intrahepatic Cholangiocarcinoma: An Immune Checkpoint With Prognostic Significance And Wider Expression Compared With Pd-L1 Background: Intrahepatic cholangiocarcinoma (ICC) is a highly mortal malignancy with limited therapeutic options. Immunotherapies targeting PD-1/PD-L1 pathway represent a promising treatment for ICC. However, PD-L1 expression and microsatellite instability are not common in ICC. This study aimed to investigate whether HHLA2, a newly identified B7 family immune checkpoint for T cells, could be a therapeutic target next to PD-L1 in ICC. \r\n\r\n Methods: Expression levels of PD-L1 and HHLA2 as well as infiltrations of CD3+, CD8+, CD4 + Foxp3+, CD68+, CD163+ and CD20+ cells were evaluated by immunohistochemistry in 153 resected ICC samples. Comprehensive comparisons were made between PD-L1 and HHLA2 in terms of the expression rates, clinicopathological features and infiltrations of different immune cells. The expression level and prognostic significance of HHLA2 were further validated in an independent cohort. \r\n\r\n Results: Expression of HHLA2 is more frequent than PD-L1 in ICC (49.0% vs 28.1%). Co-expression of both immune checkpoints was infrequent (13.1%) and 50% PD-L1 negative cases were with elevated HHLA2. HHLA2 overexpression was associated with sparser CD3+ tumor infiltrating lymphocytes (TILs), CD8+ TILs and a higher CD4 + Foxp3+/CD8+ TIL ratio, whereas PD-L1 expression was associated with prominent T cells and CD163+ tumor associated macrophages infiltrations. PD-L1 failed to stratify overall survival (OS) but HHLA2 was identified as an independent prognostic indicator for OS in two independent cohorts. \r\n\r\n Conclusions: Compared with PD-L1, HHLA2 is more prevalent and possesses more explicit prognostic significance, which confer the rationale for HHLA2 as a potential immunotherapeutic target next to PD-L1 for ICC patients. STN","prediction_labels":"HUMAN"},{"cleaned":"surgical management morbidity prognostic factors survival 70 consecutive patients hilar cholangiocarcinoma background aims hilar cholangiocarcinoma represent less 1 malignancies study conceived assess multimodal treatment including surgical approach determine postoperative morbidity mortality long term results prognostic factors methods march 2002 december 2008 70 patients klatskin tumor evaluated uz ghent clinicopathological data analyzed univariate multivariate analyses carried results fifteen seventy patients unresectable group treated palliative stenting 55 patients underwent surgery group b n 3 bismuth type ii n 18 type iiia n 23 type iiib n 11 type iv hospital mortality overall morbidity rates 5 5 32 7 respectively median fu 29 9 months 1 87 median os 3 4 group vs 29 9 group b p 0 001 right left extended hepatectomies highest r0 rate 88 2 15 17 patients three 5 years survival rates higher r0 vs r1 r2 resection 55 vs 30 41 vs 17 respectively p 0 001 identified prognostic factors r1 r2 resection lymphatic perineural invasiveness ajcc stage poor differentiation conclusion radical surgery factor improving survival acceptable surgical mortality extended hepatectomy increased r0 resections multivariate analysis incomplete resection poor differentiation perineural infiltration correlate shorter survival google scholar","probabilities":0.9799733,"Title":"Surgical Management Morbidity And Prognostic Factors Of Survival In 70 Consecutive Patients With Hilar Cholangiocarcinoma","Abstract":"Background&Aims: Hilar cholangiocarcinoma represent less\nthan 1 % of all malignancies. This study was conceived to assess multimodal\ntreatment including surgical approach and to determine\npostoperative morbidity, mortality, long-term results and prognostic\nfactors.\nMethods: From March 2002 to December 2008, 70 patients with\na Klatskin tumor were evaluated in the UZ Ghent. Clinicopathological\ndata were analyzed and univariate and multivariate analyses carried\nout.\nResults: Fifteen out of seventy patients were unresectable (group\nA) and treated with palliative stenting. The other 55 patients underwent\nsurgery (group B): n = 3 for Bismuth type II, n = 18 for type\nIIIa, n = 23 for type IIIb and n = 11 for type IV. In-hospital mortality\nand overall morbidity rates were 5.5 and 32.7 % respectively. After a\nmedian FU of 29.9 months (1–87) median OS was 3.4 (group A) vs\n29.9 (group B, p < 0.001). Right or left extended hepatectomies had\nthe highest R0 rate (88.2 % 15/17 patients). Three and 5 years survival\nrates were higher in R0 vs R1–R2 resection (55 vs 30 %, 41 vs\n17 % respectively, p < 0.001). Identified prognostic factors were: R1–\nR2 resection, lymphatic and perineural invasiveness, AJCC stage and\npoor differentiation.\nConclusion: Radical surgery is the only factor improving survival\nwith an acceptable surgical mortality. Extended hepatectomy\nincreased R0 resections. On multivariate analysis, incomplete resection,\npoor differentiation and perineural infiltration correlate with\nshorter survival.","Source":"Google Scholar","category":"HUMAN","training_data":"Surgical Management Morbidity And Prognostic Factors Of Survival In 70 Consecutive Patients With Hilar Cholangiocarcinoma Background&Aims: Hilar cholangiocarcinoma represent less\nthan 1 % of all malignancies. This study was conceived to assess multimodal\ntreatment including surgical approach and to determine\npostoperative morbidity, mortality, long-term results and prognostic\nfactors.\nMethods: From March 2002 to December 2008, 70 patients with\na Klatskin tumor were evaluated in the UZ Ghent. Clinicopathological\ndata were analyzed and univariate and multivariate analyses carried\nout.\nResults: Fifteen out of seventy patients were unresectable (group\nA) and treated with palliative stenting. The other 55 patients underwent\nsurgery (group B): n = 3 for Bismuth type II, n = 18 for type\nIIIa, n = 23 for type IIIb and n = 11 for type IV. In-hospital mortality\nand overall morbidity rates were 5.5 and 32.7 % respectively. After a\nmedian FU of 29.9 months (1–87) median OS was 3.4 (group A) vs\n29.9 (group B, p < 0.001). Right or left extended hepatectomies had\nthe highest R0 rate (88.2 % 15/17 patients). Three and 5 years survival\nrates were higher in R0 vs R1–R2 resection (55 vs 30 %, 41 vs\n17 % respectively, p < 0.001). Identified prognostic factors were: R1–\nR2 resection, lymphatic and perineural invasiveness, AJCC stage and\npoor differentiation.\nConclusion: Radical surgery is the only factor improving survival\nwith an acceptable surgical mortality. Extended hepatectomy\nincreased R0 resections. On multivariate analysis, incomplete resection,\npoor differentiation and perineural infiltration correlate with\nshorter survival. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"development immunochromatographic point care test serodiagnosis opisthorchiasis clonorchiasis chronic infections food borne liver flukes opisthorchis viverrini clonorchis sinensis associate cholangiocarcinoma bile duct cancer generally poor prognosis produced rapid simple immunochromatographic test ict kit diagnosis opisthorchiasis clonorchiasis detection igg antibodies human infection sera sera volunteers proven opisthorchiasis several parasitic diseases healthy controls evaluated presence liver fluke infection specific antibodies using preparation excretory secretory antigen adult stage o viverrini absorbed onto ict strips diagnostic values compared elisa diagnostic sensitivity specificity positive negative predictive values elisa 100 98 3 97 9 100 whereas ict 94 6 91 2 89 7 95 4 respectively 91 7 concordance ict elisa differences performance tests statistically significant p 0 05 twenty seven 30 90 clonorchiasis sera also positive ict new ict provides facile rapid test point care testing tool used bedside without need sophisticated equipment moreover ict anticipated supplement stool examination screening tool clinic diagnosis opisthorchiasis clonorchiasis addition may useful screens populations risk liver fluke infection associated cholangiocarcinoma stn","probabilities":1.0,"Title":"Development Of An Immunochromatographic Point-Of-Care Test For Serodiagnosis Of Opisthorchiasis And Clonorchiasis","Abstract":"Chronic infections with the food-borne liver flukes, Opisthorchis viverrini or Clonorchis sinensis, associate with cholangiocarcinoma, bile duct cancer, which generally has a poor prognosis. We have produced a rapid and simple immunochromatographic test (ICT) kit for the diagnosis of opisthorchiasis and clonorchiasis by the detection of IgG antibodies in human infection sera. Sera from volunteers with proven opisthorchiasis and several other parasitic diseases and from healthy controls were evaluated for the presence of liver fluke infection-specific antibodies using a preparation of excretory-secretory antigen from adult stage O. viverrini absorbed onto ICT strips. Diagnostic values were compared with an ELISA. The diagnostic sensitivity, specificity, and positive and negative predictive values of the ELISA were 100%, 98.3%, 97.9%, and 100%, whereas those for the ICT were 94.6%, 91.2%, 89.7%, and 95.4%, respectively. There was 91.7% concordance between the ICT with ELISA, and differences in performance between the tests were not statistically significant (P > 0.05). Twenty-seven of 30 (90%) of the clonorchiasis sera also were positive by ICT. This new ICT provides a facile, rapid test for point-of-care testing tool, which can be used at the bedside without the need for sophisticated equipment. Moreover, the ICT can be anticipated to supplement stool examination as a screening tool in the clinic for the diagnosis of opisthorchiasis and clonorchiasis, and in addition, it may be useful in screens of populations at risk of liver fluke infection-associated cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Development Of An Immunochromatographic Point-Of-Care Test For Serodiagnosis Of Opisthorchiasis And Clonorchiasis Chronic infections with the food-borne liver flukes, Opisthorchis viverrini or Clonorchis sinensis, associate with cholangiocarcinoma, bile duct cancer, which generally has a poor prognosis. We have produced a rapid and simple immunochromatographic test (ICT) kit for the diagnosis of opisthorchiasis and clonorchiasis by the detection of IgG antibodies in human infection sera. Sera from volunteers with proven opisthorchiasis and several other parasitic diseases and from healthy controls were evaluated for the presence of liver fluke infection-specific antibodies using a preparation of excretory-secretory antigen from adult stage O. viverrini absorbed onto ICT strips. Diagnostic values were compared with an ELISA. The diagnostic sensitivity, specificity, and positive and negative predictive values of the ELISA were 100%, 98.3%, 97.9%, and 100%, whereas those for the ICT were 94.6%, 91.2%, 89.7%, and 95.4%, respectively. There was 91.7% concordance between the ICT with ELISA, and differences in performance between the tests were not statistically significant (P > 0.05). Twenty-seven of 30 (90%) of the clonorchiasis sera also were positive by ICT. This new ICT provides a facile, rapid test for point-of-care testing tool, which can be used at the bedside without the need for sophisticated equipment. Moreover, the ICT can be anticipated to supplement stool examination as a screening tool in the clinic for the diagnosis of opisthorchiasis and clonorchiasis, and in addition, it may be useful in screens of populations at risk of liver fluke infection-associated cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"evaluation 8th edition american joint commission cancer ajcc staging system patients intrahepatic cholangiocarcinoma surveillance epidemiology end results seer analysis background objective study assess prognostic performance american joint committee cancer ajcc 8th edition patients intrahepatic cholangiocarcinoma icc using cancer registry methods surveillance epidemiology end results seer cancer registry queried identify 1008 patients underwent surgical resection icc 1998 2013 kaplan meier method cox proportional hazards regression models used analyze long term survival relative discriminative abilities assessed using harrell concordance index results median patient age 62 years 47 6 patients male tumors t1 t2 n 413 41 0 n 329 32 6 respectively 22 1 patients lymph node ln metastasis median tumor size 5 5 cm median follow 18 months median survival 27 months 5 year os 30 6 os c index ajcc 8th staging system 0 669 comparable c index 7th edition ajcc staging system c index 0 667 ajcc 8th edition provide discrete stratification patients conclusions new ajcc 8th edition staging system icc largely comparable 7th edition version provide marked improvement overall prognostic discrimination stn","probabilities":0.9799733,"Title":"Evaluation Of The 8Th Edition American Joint Commission On Cancer (Ajcc) Staging System For Patients With Intrahepatic Cholangiocarcinoma: A Surveillance Epidemiology And End Results (Seer) Analysis","Abstract":"Background: The objective of this study was to assess the prognostic performance of American Joint Committee on Cancer (AJCC) 8th edition in patients with intrahepatic cholangiocarcinoma (ICC) using a cancer registry. \r\n\r\n Methods: The Surveillance, Epidemiology, and End Results (SEER) cancer registry was queried to identify 1008 patients who underwent surgical resection of ICC during 1998-2013. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze long-term survival. The relative discriminative abilities were assessed using the Harrell's concordance index. \r\n\r\n Results: Median patient age was 62 years and 47.6% of the patients were male. Most tumors were T1 or T2 (n = 413, 41.0% and n = 329, 32.6%, respectively) and 22.1% of patients had lymph node (LN) metastasis. Median tumor size was 5.5 cm. With a median follow-up of 18 months, median survival was 27 months and 5-year OS was 30.6%. The OS c-index for the AJCC 8th staging system was 0.669, which was comparable with the c-index for the 7th edition AJCC staging system (c-index: 0.667); the AJCC 8th-edition did provide more discrete stratification of patients. \r\n\r\n Conclusions: The new AJCC 8th-edition staging system for ICC was largely comparable to the 7th-edition version and did not provide a marked improvement in overall prognostic discrimination.","Source":"STN","category":"HUMAN","training_data":"Evaluation Of The 8Th Edition American Joint Commission On Cancer (Ajcc) Staging System For Patients With Intrahepatic Cholangiocarcinoma: A Surveillance Epidemiology And End Results (Seer) Analysis Background: The objective of this study was to assess the prognostic performance of American Joint Committee on Cancer (AJCC) 8th edition in patients with intrahepatic cholangiocarcinoma (ICC) using a cancer registry. \r\n\r\n Methods: The Surveillance, Epidemiology, and End Results (SEER) cancer registry was queried to identify 1008 patients who underwent surgical resection of ICC during 1998-2013. Kaplan-Meier method and Cox proportional hazards regression models were used to analyze long-term survival. The relative discriminative abilities were assessed using the Harrell's concordance index. \r\n\r\n Results: Median patient age was 62 years and 47.6% of the patients were male. Most tumors were T1 or T2 (n = 413, 41.0% and n = 329, 32.6%, respectively) and 22.1% of patients had lymph node (LN) metastasis. Median tumor size was 5.5 cm. With a median follow-up of 18 months, median survival was 27 months and 5-year OS was 30.6%. The OS c-index for the AJCC 8th staging system was 0.669, which was comparable with the c-index for the 7th edition AJCC staging system (c-index: 0.667); the AJCC 8th-edition did provide more discrete stratification of patients. \r\n\r\n Conclusions: The new AJCC 8th-edition staging system for ICC was largely comparable to the 7th-edition version and did not provide a marked improvement in overall prognostic discrimination. STN","prediction_labels":"HUMAN"},{"cleaned":"survival analysis yttrium 90 radioembolization unresectable intrahepatic cholangiocarcinoma background intrahepatic cholangiocarcinoma icc rapidly progressing malignancy frequently presents advanced stage often chemorefractory median overall survival os best medical treatment approximately 12 months current study examines survival characterizes predictors mortality icc patients treated transarterial yttrium 90 radioembolization tare methods patients unresectable icc underwent tare may 2009 may 2016 single institution included clinicopathologic variables reviewed primary endpoint os time tare secondary endpoints included os time diagnosis post procedure toxicities predictors mortality results total 134 tare performed 85 patients average age treatment 73 4 9 3 years patients female 52 one third patients ecog 2 significant post procedure sequalae thirty six patients 42 extrahepatic disease time treatment 61 patients 72 treated systemic chemotherapy prior tare majority patients 92 9 received treatment one lobe average radiation dose 180 1 127 1 gy median os time first tare 12 months 95 ci 7 8 16 1 median os time diagnosis 21 4 months 95 ci 14 9 27 8 51 8 26 treated patients still alive 1 3 years respectively univariate analysis age treatment ecog score presence extrahepatic disease baseline albumin alkaline phosphatase ast correlated os multivariate analysis low ecog score higher baseline albumin predicted improved os p 0 01 conclusions y90 radioembolization demonstrates survival benefit patients unresectable icc compared historic controls best medical treatment considered effective therapy select patients multi institutional randomized control trial performed evaluate efficacy tare select patients 1st line salvage therapy google scholar","probabilities":0.9799733,"Title":"Survival Analysis Of Yttrium-90 Radioembolization For Unresectable Intrahepatic Cholangiocarcinoma","Abstract":"Background: Intrahepatic cholangiocarcinoma (ICC) is a rapidly progressing malignancy that frequently presents at an advanced stage and is often chemorefractory. The median overall survival (OS) with best medical treatment is approximately 12 months. The current study examines survival and characterizes predictors of mortality for ICC patients treated with transarterial yttrium-90 radioembolization (TARE). Methods: All patients with unresectable ICC who underwent TARE between May 2009 and May 2016 at a single institution were included and clinicopathologic variables reviewed. Primary endpoint was OS from time of TARE. Secondary endpoints included OS from time of diagnosis, post procedure toxicities and predictors of mortality. Results: A total of 134 TARE were performed on 85 patients. Average age at treatment was 73.4 ± 9.3 years and most patients were female (52%). More than one third of patients had an ECOG of 2 and had no significant post procedure sequalae. Thirty-six patients (42%) had extrahepatic disease at time of treatment and 61 patients (72%) were treated with systemic chemotherapy prior to TARE. A majority of patients (92.9%) received treatment to one lobe with an average radiation dose of 180.1±127.1 Gy. The median OS from time of the first TARE was 12 months (95% CI 7.8–16.1). The median OS from time of diagnosis was 21.4 months (95% CI 14.9-27.8). 51.8% and 26% of treated patients were still alive at 1 and 3 years, respectively. On univariate analysis, age at treatment, ECOG score, presence of extrahepatic disease, baseline albumin, alkaline phosphatase and AST correlated with OS. On multivariate analysis only low ECOG score and higher baseline albumin predicted improved OS (p < 0.01). Conclusions: Y90 radioembolization demonstrates a survival benefit for patients with unresectable ICC compared to historic controls of best medical treatment and should be considered an effective therapy in select patients. A multi-institutional randomized control trial should be performed to evaluate efficacy of TARE in select patients as both 1st line and salvage therapy.","Source":"Google Scholar","category":"HUMAN","training_data":"Survival Analysis Of Yttrium-90 Radioembolization For Unresectable Intrahepatic Cholangiocarcinoma Background: Intrahepatic cholangiocarcinoma (ICC) is a rapidly progressing malignancy that frequently presents at an advanced stage and is often chemorefractory. The median overall survival (OS) with best medical treatment is approximately 12 months. The current study examines survival and characterizes predictors of mortality for ICC patients treated with transarterial yttrium-90 radioembolization (TARE). Methods: All patients with unresectable ICC who underwent TARE between May 2009 and May 2016 at a single institution were included and clinicopathologic variables reviewed. Primary endpoint was OS from time of TARE. Secondary endpoints included OS from time of diagnosis, post procedure toxicities and predictors of mortality. Results: A total of 134 TARE were performed on 85 patients. Average age at treatment was 73.4 ± 9.3 years and most patients were female (52%). More than one third of patients had an ECOG of 2 and had no significant post procedure sequalae. Thirty-six patients (42%) had extrahepatic disease at time of treatment and 61 patients (72%) were treated with systemic chemotherapy prior to TARE. A majority of patients (92.9%) received treatment to one lobe with an average radiation dose of 180.1±127.1 Gy. The median OS from time of the first TARE was 12 months (95% CI 7.8–16.1). The median OS from time of diagnosis was 21.4 months (95% CI 14.9-27.8). 51.8% and 26% of treated patients were still alive at 1 and 3 years, respectively. On univariate analysis, age at treatment, ECOG score, presence of extrahepatic disease, baseline albumin, alkaline phosphatase and AST correlated with OS. On multivariate analysis only low ECOG score and higher baseline albumin predicted improved OS (p < 0.01). Conclusions: Y90 radioembolization demonstrates a survival benefit for patients with unresectable ICC compared to historic controls of best medical treatment and should be considered an effective therapy in select patients. A multi-institutional randomized control trial should be performed to evaluate efficacy of TARE in select patients as both 1st line and salvage therapy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological stratification long term follow patients periampullary carcinomas background periampullary carcinomas generally confer poor outcome choosing effective treatment regimen sub entity proves challenging usually based experience pancreatic adenocarcinoma pdac patients methods long term follow presented 472 patients periampullary tumors pdac distal cholangiocarcinoma dcc ampullary carcinomas ac underwent radical resection considering clinical characteristics paraclinical findings histopathological features order define factors prognostic relevance results patients pdacs presented larger tumor sizes frequent r1 resection higher rate nodal perineural invasion higher tumor stage according classification tumors union internationale contre le cancer compared dccs acs multivariate analysis age 65 years postoperative complications higher grading tumor proved independent prognostic factors survival conclusion patients suffering pdac worst prognosis greatest benefit radical resection patients periampullary tumors detailed studies warranted better distinguish different entities pubmed","probabilities":0.9799733,"Title":"Clinicopathological Stratification and Long-term Follow-up of Patients with Periampullary Carcinomas","Abstract":"BACKGROUND: Periampullary carcinomas generally confer a poor outcome. Choosing the most effective treatment regimen for each sub-entity proves challenging and is usually based on experience from pancreatic adenocarcinoma (PDAC). PATIENTS AND METHODS: The long-term follow-up is presented of 472 patients with periampullary tumors [PDAC, distal cholangiocarcinoma (dCC) and ampullary carcinomas (AC)] who underwent radical resection considering clinical characteristics, paraclinical findings and histopathological features in order to define factors of prognostic relevance. RESULTS: Patients with PDACs presented with larger tumor sizes, more frequent R1 resection, higher rate of nodal and perineural invasion, higher tumor stage according to the classification of tumors of the Union Internationale contre le Cancer when compared to those with dCCs and ACs. In a multivariate analysis, age >65 years, postoperative complications and higher grading of the tumor proved to be independent prognostic factors for survival. CONCLUSION: Patients suffering from PDAC have the worst prognosis and greatest benefit from radical resection of all patients with periampullary tumors. More detailed studies are warranted to better distinguish between the different entities.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological Stratification and Long-term Follow-up of Patients with Periampullary Carcinomas BACKGROUND: Periampullary carcinomas generally confer a poor outcome. Choosing the most effective treatment regimen for each sub-entity proves challenging and is usually based on experience from pancreatic adenocarcinoma (PDAC). PATIENTS AND METHODS: The long-term follow-up is presented of 472 patients with periampullary tumors [PDAC, distal cholangiocarcinoma (dCC) and ampullary carcinomas (AC)] who underwent radical resection considering clinical characteristics, paraclinical findings and histopathological features in order to define factors of prognostic relevance. RESULTS: Patients with PDACs presented with larger tumor sizes, more frequent R1 resection, higher rate of nodal and perineural invasion, higher tumor stage according to the classification of tumors of the Union Internationale contre le Cancer when compared to those with dCCs and ACs. In a multivariate analysis, age >65 years, postoperative complications and higher grading of the tumor proved to be independent prognostic factors for survival. CONCLUSION: Patients suffering from PDAC have the worst prognosis and greatest benefit from radical resection of all patients with periampullary tumors. More detailed studies are warranted to better distinguish between the different entities. PubMed","prediction_labels":"HUMAN"},{"cleaned":"glucose lymphocyte ratio prognostic marker patients resected pt2 gallbladder cancer background designed clinical application glucose lymphocyte ratio glr might sensitive parameter determine glucose metabolism behavior cancer e aggressiveness immunologic status patient cancer thus investigated association glr overall survival os disease free survival dfs patients t2 gallbladder gb cancer curative intent surgery methods medical records patients t2 gb cancer underwent surgery retrospectively reviewed clinicopathologic characteristics preoperative complete blood counts fasting blood glucose albumin cholesterol follow information collected results total 197 patients included study multivariate analysis high glr 69 3 associated poor os hr 15 249 95 ci 4 090 56 849 p 0 0001 along r1 status hr 1 755 95 ci 0 033 0 910 p 0 033 3 metastatic lymph nodes hr 2 809 95 ci 1 403 5 625 p 0 004 lymphovascular invasion hr 8 041 95 ci 2 881 22 442 p 0 0001 moreover high glr hr 3 666 95 ci 1 145 11 737 p 0 029 adjuvant chemotherapy hr 6 306 95 ci 1 921 20 699 p 0 002 lymphovascular invasion hr 5 464 95 ci 1 783 16 746 p 0 003 high grade tumor hr 2 143 95 ci 1 042 4 407 p 0 038 independently associated dfs conclusions preoperative glr independent predictor os dfs t2 gb cancer studies required validate findings pubmed","probabilities":0.9799733,"Title":"Glucose to Lymphocyte Ratio as a Prognostic Marker in Patients With Resected pT2 Gallbladder Cancer","Abstract":"BACKGROUND: We designed a clinical application of glucose to lymphocyte ratio (GLR) as it might be a sensitive parameter to determine the glucose metabolism and behavior of the cancer (i.e., its aggressiveness), and the immunologic status of a patient with cancer. Thus, we investigated the association of GLR with the overall survival (OS) and disease-free survival (DFS) of patients with T2 gallbladder (GB) cancer after curative-intent surgery. METHODS: The medical records of patients with T2 GB cancer who underwent surgery were retrospectively reviewed. The clinicopathologic characteristics, preoperative complete blood counts, fasting blood glucose, albumin, cholesterol, and follow-up information were collected. RESULTS: A total of 197 patients were included in the study. In multivariate analysis, high GLR (>69.3) was associated with poor OS (HR = 15.249, 95% CI: 4.090-56.849, P = 0.0001) along with R1 status (HR = 1.755, 95% CI: 0.033-0.910, P = 0.033), >3 metastatic lymph nodes (HR = 2.809, 95% CI: 1.403-5.625; P = 0.004), and lymphovascular invasion (HR = 8.041, 95% CI: 2.881-22.442; P = 0.0001). Moreover, high GLR (HR = 3.666, 95% CI: 1.145-11.737, P = 0.029), adjuvant chemotherapy (HR = 6.306, 95% CI: 1.921-20.699; P = 0.002), lymphovascular invasion (HR = 5.464, 95% CI: 1.783-16.746; P = 0.003), and high-grade tumor (HR = 2.143, 95% CI: 1.042-4.407; P = 0.038) were independently associated with DFS. CONCLUSIONS: Preoperative GLR is an independent predictor of OS and DFS in T2 GB cancer. Further studies are required to validate these findings.","Source":"PubMed","category":"HUMAN","training_data":"Glucose to Lymphocyte Ratio as a Prognostic Marker in Patients With Resected pT2 Gallbladder Cancer BACKGROUND: We designed a clinical application of glucose to lymphocyte ratio (GLR) as it might be a sensitive parameter to determine the glucose metabolism and behavior of the cancer (i.e., its aggressiveness), and the immunologic status of a patient with cancer. Thus, we investigated the association of GLR with the overall survival (OS) and disease-free survival (DFS) of patients with T2 gallbladder (GB) cancer after curative-intent surgery. METHODS: The medical records of patients with T2 GB cancer who underwent surgery were retrospectively reviewed. The clinicopathologic characteristics, preoperative complete blood counts, fasting blood glucose, albumin, cholesterol, and follow-up information were collected. RESULTS: A total of 197 patients were included in the study. In multivariate analysis, high GLR (>69.3) was associated with poor OS (HR = 15.249, 95% CI: 4.090-56.849, P = 0.0001) along with R1 status (HR = 1.755, 95% CI: 0.033-0.910, P = 0.033), >3 metastatic lymph nodes (HR = 2.809, 95% CI: 1.403-5.625; P = 0.004), and lymphovascular invasion (HR = 8.041, 95% CI: 2.881-22.442; P = 0.0001). Moreover, high GLR (HR = 3.666, 95% CI: 1.145-11.737, P = 0.029), adjuvant chemotherapy (HR = 6.306, 95% CI: 1.921-20.699; P = 0.002), lymphovascular invasion (HR = 5.464, 95% CI: 1.783-16.746; P = 0.003), and high-grade tumor (HR = 2.143, 95% CI: 1.042-4.407; P = 0.038) were independently associated with DFS. CONCLUSIONS: Preoperative GLR is an independent predictor of OS and DFS in T2 GB cancer. Further studies are required to validate these findings. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma treated transarterial yttrium 90 glass microsphere radioembolization results single institution retrospective study purpose evaluate efficacy safety transarterial yttrium 90 glass microsphere radioembolization patients unresectable intrahepatic cholangiocarcinoma icc materials methods retrospective review 85 consecutive patients 41 men 44 women age 73 4 9 3 years performed survival data analyzed kaplan meier method cox regression models log rank test results median overall survival os diagnosis 21 4 months 95 confidence interval ci 16 6 28 4 median os radioembolization 12 0 months 95 ci 8 0 15 2 seven episodes severe toxicity occurred 3 months 6 2 patients partial response 64 2 stable disease 29 6 progressive disease median os radioembolization significantly longer patients eastern cooperative oncology group ecog scores 0 1 patients ecog score 2 18 5 vs 5 5 months p 0012 median os radioembolization significantly longer patients well differentiated histology patients poorly differentiated histology 18 6 vs 9 7 months p 012 patients solitary tumors significantly longer median os radioembolization patients multifocal disease 25 vs 6 1 months p 006 absence extrahepatic metastasis associated significantly increased median os 15 2 vs 6 8 months p 003 increased time diagnosis radioembolization negative predictor os morphology tumor mass forming infiltrative hyper hypo enhancing effect survival post treatment increased cancer antigen 19 9 level increased international normalized ratio decreased albumin increased bilirubin increased aspartate aminotransferase increased model end stage liver disease score significant predictors decreased os conclusions data support therapeutic role radioembolization treatment unresectable icc good efficacy acceptable safety profile pubmed","probabilities":0.9799733,"Title":"Intrahepatic Cholangiocarcinoma Treated with Transarterial Yttrium-90 Glass Microsphere Radioembolization: Results of a Single Institution Retrospective Study","Abstract":"PURPOSE: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. RESULTS: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. CONCLUSIONS: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile.","Source":"PubMed","category":"HUMAN","training_data":"Intrahepatic Cholangiocarcinoma Treated with Transarterial Yttrium-90 Glass Microsphere Radioembolization: Results of a Single Institution Retrospective Study PURPOSE: To evaluate the efficacy and safety of transarterial yttrium-90 glass microsphere radioembolization in patients with unresectable intrahepatic cholangiocarcinoma (ICC). MATERIALS AND METHODS: Retrospective review of 85 consecutive patients (41 men and 44 women; age, 73.4 ± 9.3 years) was performed. Survival data were analyzed by the Kaplan-Meier method, Cox regression models, and the log-rank test. RESULTS: Median overall survival (OS) from diagnosis was 21.4 months (95% confidence interval [CI]: 16.6-28.4); median OS from radioembolization was 12.0 months (95% CI: 8.0-15.2). Seven episodes of severe toxicity occurred. At 3 months, 6.2% of patients had partial response, 64.2% had stable disease, and 29.6% had progressive disease. Median OS from radioembolization was significantly longer in patients with Eastern Cooperative Oncology Group (ECOG) scores of 0 and 1 than patients with an ECOG score of 2 (18.5 vs 5.5 months, P = .0012), and median OS from radioembolization was significantly longer in patients with well-differentiated histology than patients with poorly differentiated histology (18.6 vs 9.7 months, P = .012). Patients with solitary tumors had significantly longer median OS from radioembolization than patients with multifocal disease (25 vs. 6.1 months, P = .006). The absence of extrahepatic metastasis was associated with significantly increased median OS (15.2 vs. 6.8 months, P = .003). Increased time from diagnosis to radioembolization was a negative predictor of OS. The morphology of the tumor (mass-forming or infiltrative, hyper- or hypo-enhancing) had no effect on survival. Post-treatment increased cancer antigen 19-9 level, increased international normalized ratio, decreased albumin, increased bilirubin, increased aspartate aminotransferase, and increased Model for End-Stage Liver Disease score were significant predictors of decreased OS. CONCLUSIONS: These data support the therapeutic role of radioembolization for the treatment of unresectable ICC with good efficacy and an acceptable safety profile. PubMed","prediction_labels":"HUMAN"},{"cleaned":"review factors predicting perioperative death early outcome hepatopancreaticobiliary cancer surgery objectives context comparisons surgical outcomes risk adjustment retrospective adjustment provider surgeon results case mix hospital volume allows accurate meaningful inter provider comparison therefore essential component audit quality improvement process aim study review literature identify factors known affect prognosis hepatobiliary pancreatic cancer surgery methods pubmed used identify studies assessing risk patients undergoing resection surgery rather bypass surgery hepatobiliary pancreatic cancer results total 63 68 papers pertaining 24 609 63 654 patients underwent hepatic pancreatic resection malignancy respectively identified overall 22 generic preoperative factors predicting outcome multivariate analysis including demographics blood results preoperative biliary drainage co morbidities identified tumour characteristics proving disease specific factors operative duration transfusion operative extent vascular resection additional intra abdominal procedures also found predictive early outcome conclusions development risk adjustment model allow identification factors influence early outcome thus identify potential targets preoperative optimization allow development multicentre risk prediction model pubmed","probabilities":0.9799733,"Title":"A review of factors predicting perioperative death and early outcome in hepatopancreaticobiliary cancer surgery","Abstract":"OBJECTIVES: In the context of comparisons of surgical outcomes, risk adjustment is the retrospective adjustment of a provider's or a surgeon's results for case mix and/or hospital volume. It allows accurate, meaningful inter-provider comparison. It is therefore an essential component of any audit and quality improvement process. The aim of this study was to review the literature to identify those factors known to affect prognosis in hepatobiliary and pancreatic cancer surgery. METHODS: PubMed was used to identify studies assessing risk in patients undergoing resection surgery, rather than bypass surgery, for hepatobiliary and pancreatic cancer. RESULTS: In total, 63 and 68 papers, pertaining to 24 609 and 63 654 patients who underwent hepatic or pancreatic resection for malignancy, respectively, were identified. Overall, 22 generic preoperative factors predicting outcome on multivariate analysis, including demographics, blood results, preoperative biliary drainage and co-morbidities, were identified, with tumour characteristics proving disease-specific factors. Operative duration, transfusion, operative extent, vascular resection and additional intra-abdominal procedures were also found to be predictive of early outcome. CONCLUSIONS: The development of a risk adjustment model will allow for the identification of those factors with most influence on early outcome and will thus identify potential targets for preoperative optimization and allow for the development of a multicentre risk prediction model.","Source":"PubMed","category":"HUMAN","training_data":"A review of factors predicting perioperative death and early outcome in hepatopancreaticobiliary cancer surgery OBJECTIVES: In the context of comparisons of surgical outcomes, risk adjustment is the retrospective adjustment of a provider's or a surgeon's results for case mix and/or hospital volume. It allows accurate, meaningful inter-provider comparison. It is therefore an essential component of any audit and quality improvement process. The aim of this study was to review the literature to identify those factors known to affect prognosis in hepatobiliary and pancreatic cancer surgery. METHODS: PubMed was used to identify studies assessing risk in patients undergoing resection surgery, rather than bypass surgery, for hepatobiliary and pancreatic cancer. RESULTS: In total, 63 and 68 papers, pertaining to 24 609 and 63 654 patients who underwent hepatic or pancreatic resection for malignancy, respectively, were identified. Overall, 22 generic preoperative factors predicting outcome on multivariate analysis, including demographics, blood results, preoperative biliary drainage and co-morbidities, were identified, with tumour characteristics proving disease-specific factors. Operative duration, transfusion, operative extent, vascular resection and additional intra-abdominal procedures were also found to be predictive of early outcome. CONCLUSIONS: The development of a risk adjustment model will allow for the identification of those factors with most influence on early outcome and will thus identify potential targets for preoperative optimization and allow for the development of a multicentre risk prediction model. PubMed","prediction_labels":"HUMAN"},{"cleaned":"challenge cholangiocarcinoma dissecting molecular mechanisms insidious cancer cholangiocarcinoma fatal cancer biliary epithelium incidence increasing worldwide survival beyond year diagnosis less 5 therapeutic options known risk factors include biliary diseases primary sclerosing cholangitis parasitic infestation biliary tree cases associated underlying diseases numerous vitro vivo models well novel analytical techniques human samples helping delineate many pathways implicated disease albeit frustratingly slow pace yet however none studies translated improved patient outcome overall pathophysiology cholangiocarcinoma still poorly understood remains urgent need new approaches models improve management insidious devastating disease review take bedside bench approach discussing cholangiocarcinoma outline research opportunities future field stn","probabilities":1.0,"Title":"The Challenge Of Cholangiocarcinoma: Dissecting The Molecular Mechanisms Of An Insidious Cancer","Abstract":"Cholangiocarcinoma is a fatal cancer of the biliary epithelium and has an incidence that is increasing worldwide. Survival beyond a year of diagnosis is less than 5%, and therapeutic options are few. Known risk factors include biliary diseases such as primary sclerosing cholangitis and parasitic infestation of the biliary tree, but most cases are not associated with any of these underlying diseases. Numerous in vitro and in vivo models, as well as novel analytical techniques for human samples, are helping to delineate the many pathways implicated in this disease, albeit at a frustratingly slow pace. As yet, however, none of these studies has been translated into improved patient outcome and, overall, the pathophysiology of cholangiocarcinoma is still poorly understood. There remains an urgent need for new approaches and models to improve management of this insidious and devastating disease. In this review, we take a bedside-to-bench approach to discussing cholangiocarcinoma and outline research opportunities for the future in this field.","Source":"STN","category":"ANIMAL","training_data":"The Challenge Of Cholangiocarcinoma: Dissecting The Molecular Mechanisms Of An Insidious Cancer Cholangiocarcinoma is a fatal cancer of the biliary epithelium and has an incidence that is increasing worldwide. Survival beyond a year of diagnosis is less than 5%, and therapeutic options are few. Known risk factors include biliary diseases such as primary sclerosing cholangitis and parasitic infestation of the biliary tree, but most cases are not associated with any of these underlying diseases. Numerous in vitro and in vivo models, as well as novel analytical techniques for human samples, are helping to delineate the many pathways implicated in this disease, albeit at a frustratingly slow pace. As yet, however, none of these studies has been translated into improved patient outcome and, overall, the pathophysiology of cholangiocarcinoma is still poorly understood. There remains an urgent need for new approaches and models to improve management of this insidious and devastating disease. In this review, we take a bedside-to-bench approach to discussing cholangiocarcinoma and outline research opportunities for the future in this field. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic significance fibrinogen albumin ratio gallbladder cancer patients aim investigate prognostic role fibrinogen albumin ratio far patients gallbladder cancer gbc study methods one hundred fifty four gbc patients retrospectively analyzed received potentially curative cholecystectomy institute march 2005 december 2017 receiver operating characteristic curve roc curve used determine optimal cut offs biomarkers addition kaplan meier survival analysis well multivariate analysis applied prognostic analyses results roc curve revealed optimal cut value far 0 08 far significantly correlated age p 0 045 jaundice p 0 001 differentiation p 0 002 resection margin status p 0 001 stage p 0 001 tnm stage p 0 001 ca199 p 0 001 well albumin levels p 0 001 multivariate analysis indicated resection margin status hazard ratio hr 2 343 95 confidence interval ci 1 532 3 581 p 0 001 tnm stage p 0 035 albumin level hr 0 595 95 ci 0 385 0 921 p 0 020 far hr 2 813 95 ci 1 765 4 484 p 0 001 independent prognostic factors gbc patients conclusion elevated preoperative far significantly correlated unfavorable overall survival gbc patients elevated preoperative albumin level protective prognostic factor patients gbc preoperative far used predict prognosis gbc patients easily accessible cost effective noninvasive pubmed","probabilities":0.9799733,"Title":"Prognostic significance of the fibrinogen-to-albumin ratio in gallbladder cancer patients","Abstract":"AIM: To investigate the prognostic role of fibrinogen-to-albumin ratio (FAR) on patients with gallbladder cancer (GBC) in this study. METHODS: One hundred and fifty-four GBC patients were retrospectively analyzed, who received potentially curative cholecystectomy in our institute from March 2005 to December 2017. Receiver operating characteristic curve (ROC curve) was used to determine the optimal cut-offs for these biomarkers. In addition, Kaplan-Meier survival analysis as well as multivariate analysis were applied for prognostic analyses. RESULTS: ROC curve revealed that the optimal cut-off value for FAR was 0.08. FAR was significantly correlated with age (P = 0.045), jaundice (P < 0.001), differentiation (P = 0.002), resection margin status (P < 0.001), T stage (P < 0.001), TNM stage (P < 0.001), and CA199 (P < 0.001) as well as albumin levels (P < 0.001). Multivariate analysis indicated that the resection margin status [hazard ratio (HR): 2.343, 95% confidence interval (CI): 1.532-3.581, P < 0.001], TNM stage (P = 0.035), albumin level (HR = 0.595, 95%CI: 0.385-0.921, P = 0.020) and FAR (HR: 2.813, 95%CI: 1.765-4.484, P < 0.001) were independent prognostic factors in GBC patients. CONCLUSION: An elevated preoperative FAR was significantly correlated with unfavorable overall survival in GBC patients, while an elevated preoperative albumin level was a protective prognostic factor for patients with GBC. The preoperative FAR could be used to predict the prognosis of GBC patients, which was easily accessible, cost-effective and noninvasive.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of the fibrinogen-to-albumin ratio in gallbladder cancer patients AIM: To investigate the prognostic role of fibrinogen-to-albumin ratio (FAR) on patients with gallbladder cancer (GBC) in this study. METHODS: One hundred and fifty-four GBC patients were retrospectively analyzed, who received potentially curative cholecystectomy in our institute from March 2005 to December 2017. Receiver operating characteristic curve (ROC curve) was used to determine the optimal cut-offs for these biomarkers. In addition, Kaplan-Meier survival analysis as well as multivariate analysis were applied for prognostic analyses. RESULTS: ROC curve revealed that the optimal cut-off value for FAR was 0.08. FAR was significantly correlated with age (P = 0.045), jaundice (P < 0.001), differentiation (P = 0.002), resection margin status (P < 0.001), T stage (P < 0.001), TNM stage (P < 0.001), and CA199 (P < 0.001) as well as albumin levels (P < 0.001). Multivariate analysis indicated that the resection margin status [hazard ratio (HR): 2.343, 95% confidence interval (CI): 1.532-3.581, P < 0.001], TNM stage (P = 0.035), albumin level (HR = 0.595, 95%CI: 0.385-0.921, P = 0.020) and FAR (HR: 2.813, 95%CI: 1.765-4.484, P < 0.001) were independent prognostic factors in GBC patients. CONCLUSION: An elevated preoperative FAR was significantly correlated with unfavorable overall survival in GBC patients, while an elevated preoperative albumin level was a protective prognostic factor for patients with GBC. The preoperative FAR could be used to predict the prognosis of GBC patients, which was easily accessible, cost-effective and noninvasive. PubMed","prediction_labels":"HUMAN"},{"cleaned":"reproductive factors gallbladder bile duct cancer population based cohort study japan reproductive menstrual factors may involved etiology gallbladder cancer gbc bile duct cancer bdc however results previous epidemiological studies inconsistent investigated association reproductive menstrual factors risk gbc bdc population based prospective cohort study japan data reproductive menstrual factors collected self administered questionnaire baseline hazard ratios hrs 95 confidence intervals cis calculated using cox proportional hazard model total 55 786 women enrolled 1990 1994 included analysis 115 gbc 113 bdc cases identified 944 861 person years follow 2010 gbc irregular longer cycles moderately associated increased risk hr 2 12 95 ci 1 30 3 47 hr 1 76 95 ci 1 08 2 89 respectively effect tended greater premenopausal postmenopausal women furthermore older age first pregnancy tended associated increased risk hr 1 84 95 ci 1 03 3 29 p trend 0 036 whereas increased duration fertility tended associated decreased risk hr 0 59 95 ci 0 35 1 01 p trend 0 055 gbc clear association bdc observed finding suggests women irregular longer cycles may increased risk gbc female hormones may play important role etiology gbc pubmed","probabilities":0.9799733,"Title":"Reproductive factors and gallbladder/bile duct cancer: a population-based cohort study in Japan","Abstract":"Reproductive/menstrual factors may be involved in the etiology of gallbladder cancer (GBC) and bile duct cancer (BDC). However, the results from previous epidemiological studies have been inconsistent. We investigated the association of reproductive/menstrual factors with the risk for GBC and BDC in a population-based prospective cohort study in Japan. Data on reproductive/menstrual factors were collected through a self-administered questionnaire at baseline. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model. A total of 55 786 women enrolled between 1990 and 1994 were included in the analysis, and 115 GBC and 113 BDC cases were identified, with 944 861 person-years follow-up until 2010. For GBC, irregular and longer cycles were moderately associated with an increased risk [HR=2.12 (95% CI: 1.30-3.47) and HR=1.76 (95% CI: 1.08-2.89), respectively]. This effect tended to be greater in premenopausal than in postmenopausal women. Furthermore, older age at first pregnancy tended to be associated with an increased risk [HR=1.84 (95% CI: 1.03-3.29), P-trend=0.036], whereas increased duration of fertility tended to be associated with a decreased risk [HR=0.59 (95% CI: 0.35-1.01), P-trend=0.055] of GBC. No clear association with BDC was observed. This finding suggests that women with irregular or longer cycles may have an increased risk for GBC and female hormones may play an important role in the etiology of GBC.","Source":"PubMed","category":"HUMAN","training_data":"Reproductive factors and gallbladder/bile duct cancer: a population-based cohort study in Japan Reproductive/menstrual factors may be involved in the etiology of gallbladder cancer (GBC) and bile duct cancer (BDC). However, the results from previous epidemiological studies have been inconsistent. We investigated the association of reproductive/menstrual factors with the risk for GBC and BDC in a population-based prospective cohort study in Japan. Data on reproductive/menstrual factors were collected through a self-administered questionnaire at baseline. The hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model. A total of 55 786 women enrolled between 1990 and 1994 were included in the analysis, and 115 GBC and 113 BDC cases were identified, with 944 861 person-years follow-up until 2010. For GBC, irregular and longer cycles were moderately associated with an increased risk [HR=2.12 (95% CI: 1.30-3.47) and HR=1.76 (95% CI: 1.08-2.89), respectively]. This effect tended to be greater in premenopausal than in postmenopausal women. Furthermore, older age at first pregnancy tended to be associated with an increased risk [HR=1.84 (95% CI: 1.03-3.29), P-trend=0.036], whereas increased duration of fertility tended to be associated with a decreased risk [HR=0.59 (95% CI: 0.35-1.01), P-trend=0.055] of GBC. No clear association with BDC was observed. This finding suggests that women with irregular or longer cycles may have an increased risk for GBC and female hormones may play an important role in the etiology of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"parity risk factor hepatobiliary neoplasm meta analysis 16 studies abstract background conflicting results reported studies assessing parity risk factor hepatobiliary neoplasm methods conducted meta analysis available epidemiologic studies investigate association parity hepatobiliary neoplasm calculated dose response trends using linear model betweenstudy heterogeneity evaluated using cochran q statistic 2 index random effects meta analysis used assess summary relative risk rr per child 95 confidence interval ci results eleven eligible studies including 2021 cases provided data meta analysis summary rr hepatobiliary neoplasm highest versus lowest parity number 2 207 95 ci 1 397 3 488 statistically significant heterogeneity q 95 84 p 0 000 2 82 3 summary rr hepatobiliary neoplasm parous versus nulliparous cases 1 37 95 ci 1 159 1 624 2 43 8 p 0 001 combined rr hepatobiliary neoplasm per live birth 1 118 95 ci 1 032 1 211 2 77 0 p 0 000 observed positive association giving birth five children hepatobiliary neoplasm risk rr 2 24 95 ci 1 472 3 411 2 55 6 p 0 005 among parity numbers considered five associated highest risk hepatobiliary neoplasm elucidating mechanism underlying positive association requires detailed investigation google scholar","probabilities":0.9799733,"Title":"Parity Is A Risk Factor For Hepatobiliary Neoplasm: A Meta-Analysis Of 16 Studies","Abstract":"Abstract: Background: Conflicting results have been reported by studies assessing parity as a risk factor for hepatobiliary neoplasm. Methods: We conducted a meta-analysis of available epidemiologic studies to investigate the association of parity with hepatobiliary neoplasm and calculated dose-response trends using a linear model. Betweenstudy heterogeneity was evaluated using Cochran’s Q statistic and the I\n2 index. Random effects meta-analysis was\nused to assess the summary relative risk (RR) per child and the 95% confidence interval (CI). Results: Eleven eligible\nstudies including 2021 cases provided data for the meta-analysis. The summary RR of hepatobiliary neoplasm for\nthe highest versus lowest parity number was 2.207 (95% CI = 1.397-3.488), with statistically significant heterogeneity (Q = 95.84, P = 0.000, I\n2 = 82.3%). The summary RR of hepatobiliary neoplasm for parous versus nulliparous\ncases was 1.37 (95% CI = 1.159-1.624, I\n2 = 43.8%, P = 0.001). The combined RR of hepatobiliary neoplasm for per\nlive birth was 1.118 (95% CI = 1.032-1.211, I\n2 = 77.0%, P = 0.000). We observed a positive association between\ngiving birth to five or more children and hepatobiliary neoplasm risk, with an RR of 2.24 (95% CI = 1.472-3.411, I\n2\n= 55.6%, P = 0.005). Among the parity numbers considered, five or more was associated with the highest risk of\nhepatobiliary neoplasm. Elucidating the mechanism underlying this positive association requires further detailed\ninvestigation","Source":"Google Scholar","category":"HUMAN","training_data":"Parity Is A Risk Factor For Hepatobiliary Neoplasm: A Meta-Analysis Of 16 Studies Abstract: Background: Conflicting results have been reported by studies assessing parity as a risk factor for hepatobiliary neoplasm. Methods: We conducted a meta-analysis of available epidemiologic studies to investigate the association of parity with hepatobiliary neoplasm and calculated dose-response trends using a linear model. Betweenstudy heterogeneity was evaluated using Cochran’s Q statistic and the I\n2 index. Random effects meta-analysis was\nused to assess the summary relative risk (RR) per child and the 95% confidence interval (CI). Results: Eleven eligible\nstudies including 2021 cases provided data for the meta-analysis. The summary RR of hepatobiliary neoplasm for\nthe highest versus lowest parity number was 2.207 (95% CI = 1.397-3.488), with statistically significant heterogeneity (Q = 95.84, P = 0.000, I\n2 = 82.3%). The summary RR of hepatobiliary neoplasm for parous versus nulliparous\ncases was 1.37 (95% CI = 1.159-1.624, I\n2 = 43.8%, P = 0.001). The combined RR of hepatobiliary neoplasm for per\nlive birth was 1.118 (95% CI = 1.032-1.211, I\n2 = 77.0%, P = 0.000). We observed a positive association between\ngiving birth to five or more children and hepatobiliary neoplasm risk, with an RR of 2.24 (95% CI = 1.472-3.411, I\n2\n= 55.6%, P = 0.005). Among the parity numbers considered, five or more was associated with the highest risk of\nhepatobiliary neoplasm. Elucidating the mechanism underlying this positive association requires further detailed\ninvestigation Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"body mass index 20 specific cancers re analyses dose response meta analyses observational studies background objectives provide overview understand strength evidence extent potential biases validity claimed associations body mass index bmi risk developing cancer methods carried umbrella review comprehensively re analyzed data dose response meta analyses associations bmi risk 20 specific cancers bladder brain breast colonic rectal endometrial gallbladder gastric leukemia liver lung melanoma multiple myeloma non hodgkins lymphoma esophagus ovarian pancreatic prostate renal thyroid adding big data missed individual studies convincing evidence association defined strong statistical significance fixed effects random effects meta analyses p 0 001 95 prediction interval pi excluded null large study heterogeneity small study effects suggestive evidence defined meeting significance threshold random summary effects p 0 05 95 pi included null weak evidence defined meeting significance threshold random summary effects p 0 05 95 pi included null large study heterogeneity small study effects results convincing evidence association bmi detectable six cancers leukemia multiple myeloma pancreatic endometrial rectal renal cell carcinoma suggestive evidence detectable malignant melanoma non hodgkins lymphoma esophageal adenocarcinoma weak evidence detectable brain central nervous system tumors breast colon gall bladder lung liver ovarian thyroid cancer evidence detectable bladder gastric prostate cancer conclusions association increased bmi cancer heterogeneous across cancer types leukemia multiple myeloma pancreatic endometrial rectal renal cell carcinoma convincingly associated increased bmi dose response meta analyses pubmed","probabilities":0.962963,"Title":"Body mass index and 20 specific cancers: re-analyses of dose-response meta-analyses of observational studies","Abstract":"BACKGROUND: Objectives were to provide an overview and understand the strength of evidence and extent of potential biases and validity of claimed associations between body mass index (BMI) and risk of developing cancer. METHODS: We carried out an umbrella review and comprehensively re-analyzed the data of dose-response meta-analyses on associations between BMI and risk of 20 specific cancers (bladder, brain, breast, colonic, rectal, endometrial, gallbladder, gastric, leukemia, liver, lung, melanoma, multiple myeloma, non-Hodgkins lymphoma, esophagus, ovarian, pancreatic, prostate, renal, thyroid) by adding big data or missed individual studies. Convincing evidence for an association was defined as a strong statistical significance in fixed-effects and random-effects meta-analyses at P < 0.001, 95% prediction interval (PI) excluded null, there was no large between-study heterogeneity and no small study effects. Suggestive evidence was defined as meeting the significance threshold for the random summary effects of P < 0.05, but 95% PI included the null. Weak evidence was defined as meeting the significance threshold for the random summary effects at a P < 0.05, but 95% PI included the null and there was large between-study heterogeneity or there were small study effects. RESULTS: Convincing evidence for an association with BMI was detectable for six cancers (leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma). Suggestive evidence was detectable for malignant melanoma, non-Hodgkins lymphoma, and esophageal adenocarcinoma. Weak evidence was detectable for brain and central nervous system tumors, breast, colon, gall bladder, lung, liver, ovarian, and thyroid cancer. No evidence was detectable for bladder, gastric, and prostate cancer. CONCLUSIONS: The association of increased BMI and cancer is heterogeneous across cancer types. Leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma are convincingly associated with an increased BMI by dose-response meta-analyses.","Source":"PubMed","category":"HUMAN","training_data":"Body mass index and 20 specific cancers: re-analyses of dose-response meta-analyses of observational studies BACKGROUND: Objectives were to provide an overview and understand the strength of evidence and extent of potential biases and validity of claimed associations between body mass index (BMI) and risk of developing cancer. METHODS: We carried out an umbrella review and comprehensively re-analyzed the data of dose-response meta-analyses on associations between BMI and risk of 20 specific cancers (bladder, brain, breast, colonic, rectal, endometrial, gallbladder, gastric, leukemia, liver, lung, melanoma, multiple myeloma, non-Hodgkins lymphoma, esophagus, ovarian, pancreatic, prostate, renal, thyroid) by adding big data or missed individual studies. Convincing evidence for an association was defined as a strong statistical significance in fixed-effects and random-effects meta-analyses at P < 0.001, 95% prediction interval (PI) excluded null, there was no large between-study heterogeneity and no small study effects. Suggestive evidence was defined as meeting the significance threshold for the random summary effects of P < 0.05, but 95% PI included the null. Weak evidence was defined as meeting the significance threshold for the random summary effects at a P < 0.05, but 95% PI included the null and there was large between-study heterogeneity or there were small study effects. RESULTS: Convincing evidence for an association with BMI was detectable for six cancers (leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma). Suggestive evidence was detectable for malignant melanoma, non-Hodgkins lymphoma, and esophageal adenocarcinoma. Weak evidence was detectable for brain and central nervous system tumors, breast, colon, gall bladder, lung, liver, ovarian, and thyroid cancer. No evidence was detectable for bladder, gastric, and prostate cancer. CONCLUSIONS: The association of increased BMI and cancer is heterogeneous across cancer types. Leukemia, multiple myeloma, pancreatic, endometrial, rectal, and renal cell carcinoma are convincingly associated with an increased BMI by dose-response meta-analyses. PubMed","prediction_labels":"HUMAN"},{"cleaned":"high serum ca19 9 levels associated increased risk cholangiocarcinoma patients intrahepatic duct stones case control study background hepatolithiasis known risk factor cholangiocarcinoma cc due high risk complications accompany endoscopic surgical stone removal often difficult decide whether beneficial remove intrahepatic ductal stones conducted case control study determine risk developing cc benefit stone removal patients hepatolithiasis methods twenty three patients cc group 2002 2012 included study patient cc four control patients hepatolithiasis enrolled based age sex matching finally 115 patients hepatolithiasis enrolled results mean length time intrahepatic stones present 116 57 98 77 months cc group 80 56 101 10 months control group history gastrectomy 5 756 1 329 24 930 p 0 019 history choledochoenterostomy 4 938 1 129 21 595 p 0 034 serum ca19 9 level 1 001 1 000 1 001 p 0 022 complete removal stones 0 167 0 052 0 539 p 0 003 independent predictive factors cc patients undergone incomplete removal stones occurrence cc significantly reduced overall well subgroup patients elevated ca19 9 p 0 015 p 0 006 respectively compared patients ca19 9 22 u ml p 0 477 conclusions history gastrectomy choledochoenterostomy high levels serum ca19 9 incomplete removal stones potential predictive factors cc patients hepatolithiasis additionally complete removal stones may reduce risk cc patients high serum ca19 9 levels 22 u ml pubmed","probabilities":0.9799733,"Title":"High serum CA19-9 levels are associated with an increased risk of cholangiocarcinoma in patients with intrahepatic duct stones: a case-control study","Abstract":"BACKGROUND: Hepatolithiasis is a known risk factor for cholangiocarcinoma (CC). Due to the high risk of complications that accompany endoscopic and surgical stone removal, it is often difficult to decide whether it is beneficial to remove intrahepatic ductal stones. We conducted a case-control study to determine the risk of developing CC and the benefit of stone removal in patients with hepatolithiasis. METHODS: Twenty-three patients with CC group between 2002 and 2012 were included in this study. For each patient with CC, four control patients with hepatolithiasis were enrolled based on age and sex matching. Finally, 115 patients with hepatolithiasis were enrolled. RESULTS: The mean length of time that intrahepatic stones were present was 116.57 (± 98.77) months in the CC group and 80.56 (± 101.10) months in the control group. History of gastrectomy [OR 5.756 (1.329-24.930), p = 0.019], history of choledochoenterostomy (OR 4.938 [1.129-21.595], p = 0.034), serum CA19-9 level [OR 1.001 (1.000-1.001), p = 0.022], and complete removal of stones [OR 0.167 (0.052-0.539), p = 0.003] were independent predictive factors of CC. In patients who had undergone incomplete removal of stones, the occurrence of CC was significantly reduced overall as well as in a subgroup of patients with elevated CA19-9 (p = 0.015 and p = 0.006, respectively) compared to patients with a CA19-9 of <22 U/mL (p = 0.477). CONCLUSIONS: History of gastrectomy or choledochoenterostomy, high levels of serum CA19-9, and incomplete removal of stones were potential predictive factors of CC in patients with hepatolithiasis. Additionally, complete removal of stones may reduce the risk of CC in patients with high serum CA19-9 levels (>22 U/mL).","Source":"PubMed","category":"HUMAN","training_data":"High serum CA19-9 levels are associated with an increased risk of cholangiocarcinoma in patients with intrahepatic duct stones: a case-control study BACKGROUND: Hepatolithiasis is a known risk factor for cholangiocarcinoma (CC). Due to the high risk of complications that accompany endoscopic and surgical stone removal, it is often difficult to decide whether it is beneficial to remove intrahepatic ductal stones. We conducted a case-control study to determine the risk of developing CC and the benefit of stone removal in patients with hepatolithiasis. METHODS: Twenty-three patients with CC group between 2002 and 2012 were included in this study. For each patient with CC, four control patients with hepatolithiasis were enrolled based on age and sex matching. Finally, 115 patients with hepatolithiasis were enrolled. RESULTS: The mean length of time that intrahepatic stones were present was 116.57 (± 98.77) months in the CC group and 80.56 (± 101.10) months in the control group. History of gastrectomy [OR 5.756 (1.329-24.930), p = 0.019], history of choledochoenterostomy (OR 4.938 [1.129-21.595], p = 0.034), serum CA19-9 level [OR 1.001 (1.000-1.001), p = 0.022], and complete removal of stones [OR 0.167 (0.052-0.539), p = 0.003] were independent predictive factors of CC. In patients who had undergone incomplete removal of stones, the occurrence of CC was significantly reduced overall as well as in a subgroup of patients with elevated CA19-9 (p = 0.015 and p = 0.006, respectively) compared to patients with a CA19-9 of <22 U/mL (p = 0.477). CONCLUSIONS: History of gastrectomy or choledochoenterostomy, high levels of serum CA19-9, and incomplete removal of stones were potential predictive factors of CC in patients with hepatolithiasis. Additionally, complete removal of stones may reduce the risk of CC in patients with high serum CA19-9 levels (>22 U/mL). PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcome surgical treatment hilar cholangiocarcinoma special reference postoperative morbidity mortality background purpose radical resection hilar cholangiocarcinoma still associated significant morbidity mortality aim study analyze short term surgical outcomes validate strategies including preoperative management selection operative procedure methods surgically treated 146 consecutive patients hilar cholangiocarcinoma management strategy consisting preoperative biliary drainage portal vein embolization selection operative procedure based tumor extension hepatic reserve major hepatectomy conducted 126 patients caudate lobectomy hilar bile duct resection 20 patients results overall 5 year survival rate 35 5 overall hospital mortality morbidity rates 3 4 44 respectively hyperbilirubinemia total bilirubin 5 mg dl persisted 7 postoperative days liver abscess frequent complications five among 9 patients liver failure total bilirubin 10 mg dl encountered hospital mortality four 5 mortality patients suffered circulatory impairment remnant liver due complications multivariate analysis revealed operative time single independent significant predictive factor odds ratio 1 005 95 confidence interval 1 000 1 010 p 0 04 postoperative complications conclusions aggressive resection hilar cholangiocarcinoma performed accordance strict management strategy achieved acceptably low mortality prolonged operative time risk morbidity following hepatobiliary resection pubmed","probabilities":0.9799733,"Title":"Outcome of surgical treatment of hilar cholangiocarcinoma: a special reference to postoperative morbidity and mortality","Abstract":"BACKGROUND/PURPOSE: Radical resection for hilar cholangiocarcinoma is still associated with significant morbidity and mortality. The aim of this study was to analyze short-term surgical outcomes and to validate our strategies, including preoperative management and selection of operative procedure. METHODS: We surgically treated 146 consecutive patients with hilar cholangiocarcinoma with a management strategy consisting of preoperative biliary drainage, portal vein embolization, and selection of operative procedure based on tumor extension and hepatic reserve. Major hepatectomy was conducted in 126 patients, and caudate lobectomy or hilar bile duct resection in 20 patients. RESULTS: The overall 5-year survival rate was 35.5%, with overall in-hospital mortality and morbidity rates of 3.4 and 44%, respectively. Hyperbilirubinemia (total bilirubin >5 mg/dL, persisted for >7 postoperative days) and liver abscess were the most frequent complications. Five among 9 patients with liver failure (total bilirubin >10 mg/dL) encountered in-hospital mortality. Four out of 5 mortality patients had suffered circulatory impairment of the remnant liver due to other complications. Multivariate analysis revealed that operative time is a single independent significant predictive factor (odds ratio, 1.005; 95% confidence interval, 1.000-1.010, P = 0.04) for postoperative complications. CONCLUSIONS: Aggressive resection for hilar cholangiocarcinoma, performed in accordance with strict management strategy, achieved acceptably low mortality. Prolonged operative time was a risk for morbidity following hepatobiliary resection.","Source":"PubMed","category":"HUMAN","training_data":"Outcome of surgical treatment of hilar cholangiocarcinoma: a special reference to postoperative morbidity and mortality BACKGROUND/PURPOSE: Radical resection for hilar cholangiocarcinoma is still associated with significant morbidity and mortality. The aim of this study was to analyze short-term surgical outcomes and to validate our strategies, including preoperative management and selection of operative procedure. METHODS: We surgically treated 146 consecutive patients with hilar cholangiocarcinoma with a management strategy consisting of preoperative biliary drainage, portal vein embolization, and selection of operative procedure based on tumor extension and hepatic reserve. Major hepatectomy was conducted in 126 patients, and caudate lobectomy or hilar bile duct resection in 20 patients. RESULTS: The overall 5-year survival rate was 35.5%, with overall in-hospital mortality and morbidity rates of 3.4 and 44%, respectively. Hyperbilirubinemia (total bilirubin >5 mg/dL, persisted for >7 postoperative days) and liver abscess were the most frequent complications. Five among 9 patients with liver failure (total bilirubin >10 mg/dL) encountered in-hospital mortality. Four out of 5 mortality patients had suffered circulatory impairment of the remnant liver due to other complications. Multivariate analysis revealed that operative time is a single independent significant predictive factor (odds ratio, 1.005; 95% confidence interval, 1.000-1.010, P = 0.04) for postoperative complications. CONCLUSIONS: Aggressive resection for hilar cholangiocarcinoma, performed in accordance with strict management strategy, achieved acceptably low mortality. Prolonged operative time was a risk for morbidity following hepatobiliary resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"development preoperative risk score postoperative mortality liver resection presumed perihilar cholangiocarcinoma background liver surgery perihilar cholangiocarcinoma phc associated postoperative mortality ranging 5 18 aim study develop preoperative risk score postoperative mortality liver resection phc assess effect biliary drainage future liver remnant flr study design consecutive series 287 patients submitted major liver resection presumed phc 1997 2014 2 western centers analyzed 228 patients 79 underwent preoperative drainage jaundice future liver remnant volumes calculated ct volumetry completeness flr drainage assessed imaging logistic regression used develop mortality risk score results postoperative mortality 90 days 14 independently predicted age odds ratio per 10 years 2 1 preoperative cholangitis 4 1 flr volume 30 2 9 portal vein reconstruction 2 3 incomplete flr drainage patients flr volume 50 2 8 risk score showed good discrimination area curve 0 75 bootstrap validation ranking patients tertiles identified 3 ie low intermediate high risk subgroups predicted mortalities 2 11 37 postoperative mortality observed 33 undrained patients flr volumes 50 including 10 jaundiced patients median bilirubin level 11 mg dl conclusions mortality risk score patients resectable phc used patient counseling identification modifiable risk factors include flr volume flr drainage status preoperative cholangitis found evidence support preoperative biliary drainage patients flr volume 50 stn","probabilities":0.9799733,"Title":"Development Of A Preoperative Risk Score For Postoperative Mortality After Liver Resection For Presumed Perihilar Cholangiocarcinoma","Abstract":"Background: Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR). \n\n Study design: A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score. \n\n Results: Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio [OR] per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume <30% (OR = 2.9), portal vein reconstruction (OR = 2.3), and incomplete FLR drainage in patients with FLR volume <50% (OR = 2.8). The risk score showed good discrimination (area under the curve = 0.75 after bootstrap validation) and ranking patients in tertiles identified 3 (ie low, intermediate, and high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes >50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL). \n\n Conclusions: The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume >50%.","Source":"STN","category":"HUMAN","training_data":"Development Of A Preoperative Risk Score For Postoperative Mortality After Liver Resection For Presumed Perihilar Cholangiocarcinoma Background: Liver surgery for perihilar cholangiocarcinoma (PHC) is associated with postoperative mortality ranging from 5% to 18%. The aim of this study was to develop a preoperative risk score for postoperative mortality after liver resection for PHC, and to assess the effect of biliary drainage of the future liver remnant (FLR). \n\n Study design: A consecutive series of 287 patients submitted to major liver resection for presumed PHC between 1997 and 2014 at 2 Western centers was analyzed; 228 patients (79%) underwent preoperative drainage for jaundice. Future liver remnant volumes were calculated with CT volumetry and completeness of FLR drainage was assessed on imaging. Logistic regression was used to develop a mortality risk score. \n\n Results: Postoperative mortality at 90 days was 14% and was independently predicted by age (odds ratio [OR] per 10 years = 2.1), preoperative cholangitis (OR = 4.1), FLR volume <30% (OR = 2.9), portal vein reconstruction (OR = 2.3), and incomplete FLR drainage in patients with FLR volume <50% (OR = 2.8). The risk score showed good discrimination (area under the curve = 0.75 after bootstrap validation) and ranking patients in tertiles identified 3 (ie low, intermediate, and high) risk subgroups with predicted mortalities of 2%, 11%, and 37%. No postoperative mortality was observed in 33 undrained patients with FLR volumes >50%, including 10 jaundiced patients (median bilirubin level 11 mg/dL). \n\n Conclusions: The mortality risk score for patients with resectable PHC can be used for patient counseling and identification of modifiable risk factors, which include FLR volume, FLR drainage status, and preoperative cholangitis. We found no evidence to support preoperative biliary drainage in patients with an FLR volume >50%. STN","prediction_labels":"HUMAN"},{"cleaned":"common transcriptional programs role chemokine c c motif ligand 20 ccl20 cell migration cholangiocarcinoma incidence cholangiocarcinoma cca risen many countries still appropriate screening treatment available growing number microarray data published todays powerful resource discovery biomarkers tackle challenges management cca study analyzed multiple microarray datasets identify common transcriptional networks cca select possible biomarker functional study cca cell lines systematic searching identified 4 microarray datasets gene expression omnibus geo repository pubmed articles differential expression analysis tumor normal tissues performed dataset order characterize common expression pattern differentially expressed genes degs datasets combined visualized hierarchical clustering heatmap gene enrichment analysis performed cluster revealed expressed degs enriched cell cycle cell migration response cytokines expressed degs enriched metabolic processes oxidation reduction lipid drug explain tumor characteristics genes enriched cell migration response cytokines investigated among genes ccl20 selected functional study role never studied cca moreover signaling may regulated disrupting receptor ccr6 treatment recombinant ccl20 induced higher cell migration increased expression n cad contrast knockdown ccr6 sirna reduced cell migration ability decreased n cadherin level altogether results suggested contribution ccl20 ccr6 signaling cell migration epithelial mesenchymal transition process thus ccl20 ccr6 signaling might target management cca stn","probabilities":0.875,"Title":"Common Transcriptional Programs And The Role Of Chemokine (C-C Motif) Ligand 20 (Ccl20) In Cell Migration Of Cholangiocarcinoma","Abstract":"The incidence of cholangiocarcinoma (CCA) has risen in many countries, but there is still no appropriate screening and treatment available. The growing number of microarray data published todays can be a powerful resource for the discovery of biomarkers to tackle challenges in the management of CCA. This study analyzed multiple microarray datasets to identify the common transcriptional networks in CCA and select a possible biomarker for functional study in CCA cell lines. A systematic searching identified 4 microarray datasets from Gene Expression Omnibus (GEO) repository and PubMed articles. Differential expression analysis between tumor and normal tissues was performed in each dataset. In order to characterize the common expression pattern, differentially expressed genes (DEGs) from all datasets were combined and visualized by hierarchical clustering and heatmap. Gene enrichment analysis performed in each cluster revealed that over-expressed DEGs were enriched in cell cycle, cell migration and response to cytokines while under-expressed DEGs were enriched in metabolic processes such as oxidation-reduction, lipid, and drug. To explain tumor characteristics, genes enriched in cell migration and response to cytokines were further investigated. Among these genes, CCL20 was selected for functional study because its role has never been studied in CCA. Moreover, its signaling may be regulated by disrupting its only receptor, CCR6. Treatment with recombinant CCL20 induced higher cell migration and increased expression of N-cad. In contrast, knockdown of CCR6 by siRNA reduced cell migration ability and decreased N-cadherin level. Altogether, these results suggested the contribution of CCL20/CCR6 signaling in cell migration through epithelial-mesenchymal transition process. Thus, CCL20/CCR6 signaling might be a target for the management of CCA.","Source":"STN","category":"ANIMAL","training_data":"Common Transcriptional Programs And The Role Of Chemokine (C-C Motif) Ligand 20 (Ccl20) In Cell Migration Of Cholangiocarcinoma The incidence of cholangiocarcinoma (CCA) has risen in many countries, but there is still no appropriate screening and treatment available. The growing number of microarray data published todays can be a powerful resource for the discovery of biomarkers to tackle challenges in the management of CCA. This study analyzed multiple microarray datasets to identify the common transcriptional networks in CCA and select a possible biomarker for functional study in CCA cell lines. A systematic searching identified 4 microarray datasets from Gene Expression Omnibus (GEO) repository and PubMed articles. Differential expression analysis between tumor and normal tissues was performed in each dataset. In order to characterize the common expression pattern, differentially expressed genes (DEGs) from all datasets were combined and visualized by hierarchical clustering and heatmap. Gene enrichment analysis performed in each cluster revealed that over-expressed DEGs were enriched in cell cycle, cell migration and response to cytokines while under-expressed DEGs were enriched in metabolic processes such as oxidation-reduction, lipid, and drug. To explain tumor characteristics, genes enriched in cell migration and response to cytokines were further investigated. Among these genes, CCL20 was selected for functional study because its role has never been studied in CCA. Moreover, its signaling may be regulated by disrupting its only receptor, CCR6. Treatment with recombinant CCL20 induced higher cell migration and increased expression of N-cad. In contrast, knockdown of CCR6 by siRNA reduced cell migration ability and decreased N-cadherin level. Altogether, these results suggested the contribution of CCL20/CCR6 signaling in cell migration through epithelial-mesenchymal transition process. Thus, CCL20/CCR6 signaling might be a target for the management of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"matched pair analysis laparoscopic versus open pancreaticoduodenectomy oncological outcomes using leeds pathology protocol background laparoscopic pancreaticoduodenectomy lpd safe procedure oncological safety lpd still matter debate study aimed compare oncological outcomes terms adequacy resection recurrence rate following lpd open pancreaticoduodenectomy opd methods november 2005 april 2009 12 lpds 9 ampullary 3 distal common bile duct tumors performed cohort 12 opds matched age gender body mass index bmi american society anesthesiologists asa score tumor site results mean tumor size lpd vs opd 19 8 vs 19 2 mm p 0 870 r0 resection achieved 9 lpd vs 8 opd p 1 000 mean number metastatic lymph nodes total number resected lpd vs opd 1 1 vs 2 1 p 0 140 20 7 vs 18 5 p 0 534 respectively clavien complications grade ii 5 vs 8 iii iv 2 vs 6 pancreatic leak 2 vs 1 statistically significant lpd vs opd mean high dependency unit hdu stay longer opd 3 7 vs 1 4 days p 0 001 2 recurrences lpd opd log rank p 0 983 overall mortality lpd vs opd 3 vs 6 log rank p 0 283 recurrence related mortality 2 vs 1 one death within 30 days opd group secondary severe sepsis none lpd group conclusions compared open procedure lpd achieved similar rate r0 resection lymph node harvest long term recurrence tumors less 2 cm though technically challenging lpd safe compromise oncological outcome pubmed","probabilities":0.9799733,"Title":"A matched-pair analysis of laparoscopic versus open pancreaticoduodenectomy: oncological outcomes using Leeds Pathology Protocol","Abstract":"BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is a safe procedure. Oncological safety of LPD is still a matter for debate. This study aimed to compare the oncological outcomes, in terms of adequacy of resection and recurrence rate following LPD and open pancreaticoduodenectomy (OPD). METHODS: Between November 2005 and April 2009, 12 LPDs (9 ampullary and 3 distal common bile duct tumors) were performed. A cohort of 12 OPDs were matched for age, gender, body mass index (BMI) and American Society of Anesthesiologists (ASA) score and tumor site. RESULTS: Mean tumor size LPD vs OPD (19.8 vs 19.2 mm, P=0.870). R0 resection was achieved in 9 LPD vs 8 OPD (P=1.000). The mean number of metastatic lymph nodes and total number resected for LPD vs OPD were 1.1 vs 2.1 (P=0.140) and 20.7 vs 18.5 (P=0.534) respectively. Clavien complications grade I/II (5 vs 8), III/IV (2 vs 6) and pancreatic leak (2 vs 1) were statistically not significant (LPD vs OPD). The mean high dependency unit (HDU) stay was longer in OPD (3.7 vs 1.4 days, P<0.001). There were 2 recurrences each in LPD and OPD (log-rank, P=0.983). Overall mortality for LPD vs OPD was 3 vs 6 (log-rank, P=0.283) and recurrence-related mortality was 2 vs 1. There was one death within 30 days in the OPD group secondary to severe sepsis and none in the LPD group. CONCLUSIONS: Compared to open procedure, LPD achieved a similar rate of R0 resection, lymph node harvest and long-term recurrence for tumors less than 2 cm. Though technically challenging, LPD is safe and does not compromise oncological outcome.","Source":"PubMed","category":"HUMAN","training_data":"A matched-pair analysis of laparoscopic versus open pancreaticoduodenectomy: oncological outcomes using Leeds Pathology Protocol BACKGROUND: Laparoscopic pancreaticoduodenectomy (LPD) is a safe procedure. Oncological safety of LPD is still a matter for debate. This study aimed to compare the oncological outcomes, in terms of adequacy of resection and recurrence rate following LPD and open pancreaticoduodenectomy (OPD). METHODS: Between November 2005 and April 2009, 12 LPDs (9 ampullary and 3 distal common bile duct tumors) were performed. A cohort of 12 OPDs were matched for age, gender, body mass index (BMI) and American Society of Anesthesiologists (ASA) score and tumor site. RESULTS: Mean tumor size LPD vs OPD (19.8 vs 19.2 mm, P=0.870). R0 resection was achieved in 9 LPD vs 8 OPD (P=1.000). The mean number of metastatic lymph nodes and total number resected for LPD vs OPD were 1.1 vs 2.1 (P=0.140) and 20.7 vs 18.5 (P=0.534) respectively. Clavien complications grade I/II (5 vs 8), III/IV (2 vs 6) and pancreatic leak (2 vs 1) were statistically not significant (LPD vs OPD). The mean high dependency unit (HDU) stay was longer in OPD (3.7 vs 1.4 days, P<0.001). There were 2 recurrences each in LPD and OPD (log-rank, P=0.983). Overall mortality for LPD vs OPD was 3 vs 6 (log-rank, P=0.283) and recurrence-related mortality was 2 vs 1. There was one death within 30 days in the OPD group secondary to severe sepsis and none in the LPD group. CONCLUSIONS: Compared to open procedure, LPD achieved a similar rate of R0 resection, lymph node harvest and long-term recurrence for tumors less than 2 cm. Though technically challenging, LPD is safe and does not compromise oncological outcome. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extrahepatic bile duct cancers surgery alone versus surgery plus postoperative radiation therapy purpose goal study determine role radiotherapy curative intent surgery management extrahepatic bile duct ehbd cancers methods materials 1997 2005 78 patients ehbd cancer surgically staged patients stratified absence adjuvant radiation n 47 group versus radiation n 31 group ii resection pathology examination showed 27 cases group 20 cases group ii microscopically positive resection margins patients group ii received 45 54 gy external beam radiotherapy primary endpoints study overall survival disease free survival prognostic factors results differences 5 year overall survival rates two groups 11 6 group vs 21 group ii however patients microscopically positive resection margins received adjuvant radiation therapy higher median disease free survival rates underwent surgery alone 21 months vs 10 months respectively p 0 042 decreasing local failure found patients received postoperative radiotherapy 61 7 group 35 6 group ii p 0 02 outcomes patients positive resection margin lymph node metastasis received postoperative radiation therapy doubled compared patients without adjuvant radiotherapy resection margin status lymph node metastasis pathology differentiation significant prognostic factors disease free survival conclusions adjuvant radiotherapy might useful patients ehbd cancer especially patients microscopic residual tumors positive lymph nodes resection increasing local control pubmed","probabilities":0.9799733,"Title":"Extrahepatic bile duct cancers: surgery alone versus surgery plus postoperative radiation therapy","Abstract":"PURPOSE: The goal of this study was to determine the role of radiotherapy after curative-intent surgery in the management of extrahepatic bile duct (EHBD) cancers. METHODS AND MATERIALS: From 1997 through 2005, 78 patients with EHBD cancer were surgically staged. These patients were stratified by the absence of adjuvant radiation (n = 47, group I) versus radiation (n = 31, group II) after resection. Pathology examination showed 27 cases in group I and 20 cases in group II had microscopically positive resection margins. The patients in group II received 45 to 54 Gy of external beam radiotherapy. The primary endpoints of this study were overall survival, disease-free survival, and prognostic factors. RESULTS: There were no differences between the 5-year overall survival rates for the two groups (11.6% in group I vs. 21% in group II). However, the patients with microscopically positive resection margins who received adjuvant radiation therapy had higher median disease-free survival rates than those who underwent surgery alone (21 months vs. 10 months, respectively, p = 0.042). Decreasing local failure was found in patients who received postoperative radiotherapy (61.7% in group I and 35.6% in group II, p = 0.02). Outcomes of the patients with a positive resection margin and lymph node metastasis who received postoperative radiation therapy were doubled compared to those of patients without adjuvant radiotherapy. Resection margin status, lymph node metastasis, and pathology differentiation were significant prognostic factors in disease-free survival. CONCLUSIONS: Adjuvant radiotherapy might be useful in patients with EHBD cancer, especially for those patients with microscopic residual tumors and positive lymph nodes after resection for increasing local control.","Source":"PubMed","category":"HUMAN","training_data":"Extrahepatic bile duct cancers: surgery alone versus surgery plus postoperative radiation therapy PURPOSE: The goal of this study was to determine the role of radiotherapy after curative-intent surgery in the management of extrahepatic bile duct (EHBD) cancers. METHODS AND MATERIALS: From 1997 through 2005, 78 patients with EHBD cancer were surgically staged. These patients were stratified by the absence of adjuvant radiation (n = 47, group I) versus radiation (n = 31, group II) after resection. Pathology examination showed 27 cases in group I and 20 cases in group II had microscopically positive resection margins. The patients in group II received 45 to 54 Gy of external beam radiotherapy. The primary endpoints of this study were overall survival, disease-free survival, and prognostic factors. RESULTS: There were no differences between the 5-year overall survival rates for the two groups (11.6% in group I vs. 21% in group II). However, the patients with microscopically positive resection margins who received adjuvant radiation therapy had higher median disease-free survival rates than those who underwent surgery alone (21 months vs. 10 months, respectively, p = 0.042). Decreasing local failure was found in patients who received postoperative radiotherapy (61.7% in group I and 35.6% in group II, p = 0.02). Outcomes of the patients with a positive resection margin and lymph node metastasis who received postoperative radiation therapy were doubled compared to those of patients without adjuvant radiotherapy. Resection margin status, lymph node metastasis, and pathology differentiation were significant prognostic factors in disease-free survival. CONCLUSIONS: Adjuvant radiotherapy might be useful in patients with EHBD cancer, especially for those patients with microscopic residual tumors and positive lymph nodes after resection for increasing local control. PubMed","prediction_labels":"HUMAN"},{"cleaned":"factors predicting survival pathological subtype patients ampullary adenocarcinoma background carcinoma ampulla vater uncommon study aimed clarify predictors survival ampullary adenocarcinoma identify characteristics two major pathological subtypes methods medical records reviewed 86 patients underwent curative resection ampullary adenocarcinoma 2000 2012 12 principal hospitals kagawa japan results resection common among 75 79 year old patients actuarial 1 3 5 year postoperative survival rates ampullary adenocarcinoma 90 72 3 69 1 respectively preoperative biliary drainage serum ca19 9 total bilirubin levels pathological grade perineural vascular pancreatic duodenal invasion nodal metastasis uicc stage pancreatobiliary subtype predictors poor survival elevated serum ca19 9 level elevated total bilirubin level lymphatic vascular perineural pancreatic invasion advanced overall tumor stage common patients pancreatobiliary type tumors patients intestinal type tumors additionally pathologic subtype analysis showed subtype distinct prognostic factors conclusions preoperative elevated serum ca19 9 total bilirubin levels prognostic factors ampullary adenocarcinoma associated pancreatobiliary type tumors surgeons aware factors pancreatobiliary type adenocarcinoma aggressively invasive associated poor survival pubmed","probabilities":0.9799733,"Title":"Factors predicting survival and pathological subtype in patients with ampullary adenocarcinoma","Abstract":"BACKGROUND: Carcinoma of the ampulla of Vater is uncommon. This study aimed to clarify predictors of survival for ampullary adenocarcinoma and to identify characteristics of its two major pathological subtypes. METHODS: Medical records were reviewed for 86 patients who underwent curative resection for ampullary adenocarcinoma between 2000 and 2012 at 12 principal hospitals in Kagawa, Japan. RESULTS: Resection was most common among 75-79-year-old patients. Actuarial 1-, 3-, and 5-year postoperative survival rates for ampullary adenocarcinoma were 90%, 72.3%, and 69.1%, respectively. Preoperative biliary drainage; serum CA19-9 and total bilirubin levels; pathological grade; perineural, vascular, pancreatic, and duodenal invasion; nodal metastasis; UICC-T stage; and pancreatobiliary subtype were predictors of poor survival. An elevated serum CA19-9 level; an elevated total bilirubin level; lymphatic, vascular, perineural, and pancreatic invasion; and advanced overall tumor stage were more common in patients with pancreatobiliary-type tumors than in patients with intestinal-type tumors. Additionally, pathologic subtype analysis showed that each subtype had distinct prognostic factors. CONCLUSIONS: Preoperative elevated serum CA19-9 and total bilirubin levels are prognostic factors for ampullary adenocarcinoma, and are both associated with pancreatobiliary-type tumors. Surgeons should be aware of these factors because pancreatobiliary-type adenocarcinoma is aggressively invasive and is associated with poor survival.","Source":"PubMed","category":"HUMAN","training_data":"Factors predicting survival and pathological subtype in patients with ampullary adenocarcinoma BACKGROUND: Carcinoma of the ampulla of Vater is uncommon. This study aimed to clarify predictors of survival for ampullary adenocarcinoma and to identify characteristics of its two major pathological subtypes. METHODS: Medical records were reviewed for 86 patients who underwent curative resection for ampullary adenocarcinoma between 2000 and 2012 at 12 principal hospitals in Kagawa, Japan. RESULTS: Resection was most common among 75-79-year-old patients. Actuarial 1-, 3-, and 5-year postoperative survival rates for ampullary adenocarcinoma were 90%, 72.3%, and 69.1%, respectively. Preoperative biliary drainage; serum CA19-9 and total bilirubin levels; pathological grade; perineural, vascular, pancreatic, and duodenal invasion; nodal metastasis; UICC-T stage; and pancreatobiliary subtype were predictors of poor survival. An elevated serum CA19-9 level; an elevated total bilirubin level; lymphatic, vascular, perineural, and pancreatic invasion; and advanced overall tumor stage were more common in patients with pancreatobiliary-type tumors than in patients with intestinal-type tumors. Additionally, pathologic subtype analysis showed that each subtype had distinct prognostic factors. CONCLUSIONS: Preoperative elevated serum CA19-9 and total bilirubin levels are prognostic factors for ampullary adenocarcinoma, and are both associated with pancreatobiliary-type tumors. Surgeons should be aware of these factors because pancreatobiliary-type adenocarcinoma is aggressively invasive and is associated with poor survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"fibroblast growth factor receptor fgfr signaling activation culminates mcl 1 regulated tumor survival pathway cc herein identified cross talk hippo fibroblast growth factor receptor fgfr oncogenic signaling pathways cholangiocarcinoma cca yes associated protein yap nuclear localization regulation canonical target genes observed cca cell lines patient derived xenograft pdx expression fgfr1 2 4 identified human cca cell lines driven part yap coactivation tbx5 turn fgfr signaling cell line minimal basal yap expression induced cellular protein expression nuclear localization treatment yap positive cca cell lines bgj398 pan fgfr inhibitor resulted decrease yap activation fgfr activation yap appears driven largely fgf5 activation fgfr2 sirna silencing ligand receptor respectively inhibited yap nuclear localization bgj398 treatment yap expressing cells induced cell death due mcl 1 depletion yap associated mouse model cca expression fgfr 1 2 4 also significantly increased accordingly bgj398 treatment tumor suppressive model yap positive pdx model preclinical data suggest yap hippo signaling pathways culminate mcl 1 regulated tumor survival pathway also nuclear yap expression may biomarker employ fgfr directed therapy stn","probabilities":0.9467213,"Title":"Fibroblast Growth Factor Receptor (Fgfr) Signaling Activation Culminates In A Mcl-1 Regulated Tumor Survival Pathway In Cc","Abstract":"Herein, we have identified cross-talk between the Hippo and fibroblast growth factor receptor (FGFR) oncogenic signaling pathways in cholangiocarcinoma (CCA). Yes-associated protein (YAP) nuclear localization and up-regulation of canonical target genes was observed in CCA cell lines and a patient-derived xenograft (PDX). Expression of FGFR1, -2, and -4 was identified in human CCA cell lines, driven, in part, by YAP coactivation of TBX5. In turn, FGFR signaling in a cell line with minimal basal YAP expression induced its cellular protein expression and nuclear localization. Treatment of YAP-positive CCA cell lines with BGJ398, a pan-FGFR inhibitor, resulted in a decrease in YAP activation. FGFR activation of YAP appears to be driven largely by FGF5 activation of FGFR2, as siRNA silencing of this ligand or receptor, respectively, inhibited YAP nuclear localization. BGJ398 treatment of YAP-expressing cells induced cell death due to Mcl-1 depletion. In a YAP-associated mouse model of CCA, expression of FGFR 1, 2, and 4 was also significantly increased. Accordingly, BGJ398 treatment was tumor-suppressive in this model and in a YAP-positive PDX model. These preclinical data suggest not only that the YAP and Hippo signaling pathways culminate in an Mcl-1-regulated tumor survival pathway but also that nuclear YAP expression may be a biomarker to employ in FGFR-directed therapy.","Source":"STN","category":"ANIMAL","training_data":"Fibroblast Growth Factor Receptor (Fgfr) Signaling Activation Culminates In A Mcl-1 Regulated Tumor Survival Pathway In Cc Herein, we have identified cross-talk between the Hippo and fibroblast growth factor receptor (FGFR) oncogenic signaling pathways in cholangiocarcinoma (CCA). Yes-associated protein (YAP) nuclear localization and up-regulation of canonical target genes was observed in CCA cell lines and a patient-derived xenograft (PDX). Expression of FGFR1, -2, and -4 was identified in human CCA cell lines, driven, in part, by YAP coactivation of TBX5. In turn, FGFR signaling in a cell line with minimal basal YAP expression induced its cellular protein expression and nuclear localization. Treatment of YAP-positive CCA cell lines with BGJ398, a pan-FGFR inhibitor, resulted in a decrease in YAP activation. FGFR activation of YAP appears to be driven largely by FGF5 activation of FGFR2, as siRNA silencing of this ligand or receptor, respectively, inhibited YAP nuclear localization. BGJ398 treatment of YAP-expressing cells induced cell death due to Mcl-1 depletion. In a YAP-associated mouse model of CCA, expression of FGFR 1, 2, and 4 was also significantly increased. Accordingly, BGJ398 treatment was tumor-suppressive in this model and in a YAP-positive PDX model. These preclinical data suggest not only that the YAP and Hippo signaling pathways culminate in an Mcl-1-regulated tumor survival pathway but also that nuclear YAP expression may be a biomarker to employ in FGFR-directed therapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"epidemiology gallbladder bile duct malignancies czech republic overview epidemiology focused tumors bile ducts gallbladder based data national cancer registry newly validated published data 2016 recent period 2012 2016 1013 patients annually average diagnosed tumors bile ducts gallbladder czech republic time average annual mortality disease reached value 836 prevalence bile ducts gallbladder cancer reached 1723 2016 comparison value measured 2006 increased 28 50 bile ducts gallbladder cancers diagnosed advanced clinical stages stage iii makes prognosis patients worse limits reachable results therapy pubmed","probabilities":0.9799733,"Title":"Epidemiology of gallbladder and bile duct malignancies in the Czech Republic","Abstract":"Overview of epidemiology focused on tumors of the bile ducts and gallbladder is based on data of the National Cancer Registry and its newly validated and published data from 2016. In most recent period 2012-2016, 1013 patients were annually (in average) diagnosed with tumors of the bile ducts and gallbladder in the Czech Republic. In the same time, average annual mortality of this disease reached value 836. Prevalence of bile ducts and gallbladder cancer reached 1723 in 2016 and in comparison, with the value measured in 2006, it increased by 28 %. More than 50 % of bile ducts and gallbladder cancers are diagnosed in advanced clinical stages (stage III+) which makes prognosis of patients worse and limits reachable results of therapy.","Source":"PubMed","category":"HUMAN","training_data":"Epidemiology of gallbladder and bile duct malignancies in the Czech Republic Overview of epidemiology focused on tumors of the bile ducts and gallbladder is based on data of the National Cancer Registry and its newly validated and published data from 2016. In most recent period 2012-2016, 1013 patients were annually (in average) diagnosed with tumors of the bile ducts and gallbladder in the Czech Republic. In the same time, average annual mortality of this disease reached value 836. Prevalence of bile ducts and gallbladder cancer reached 1723 in 2016 and in comparison, with the value measured in 2006, it increased by 28 %. More than 50 % of bile ducts and gallbladder cancers are diagnosed in advanced clinical stages (stage III+) which makes prognosis of patients worse and limits reachable results of therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression cell cycle related proteins p16 p53 p63 important prognostic markers gallbladder adenocarcinoma gallbladder cancer common biliary tract malignancy highly malignant neoplasm present work analyzed significance cell cycle related proteins predict prognosis provide guidance optimal therapeutic decision making patients gallbladder adenocarcinoma expressions p16 p21 p27 p53 p63 cyclin d1 bcl 2 bcl 6 examined tissue microarray constructed 96 cases gallbladder adenocarcinoma immunohistochemistry correlated clinicopathologic prognostic factors expression p16 correlated low pt stage adenoma background good prognosis cases p63 expression showed higher stage frequent perineural invasion poor prognosis compared cases without p63 expression expression p53 loss p53 associated poor tumor differentiation frequent distant metastasis low disease specific survival rate expressions p21 p27 bcl 2 bcl 6 cyclin d1 significant prognostic factors gallbladder adenocarcinoma results indicate p16 p63 p53 used prognostic markers gallbladder adenocarcinoma especially p53 p63 poor prognostic markers p16 favorable prognostic marker pubmed","probabilities":0.962963,"Title":"Expression of cell cycle-related proteins, p16, p53 and p63 as important prognostic markers in gallbladder adenocarcinoma","Abstract":"Gallbladder cancer, the most common biliary tract malignancy, is a highly malignant neoplasm. In the present work, we have analyzed the significance of cell cycle-related proteins to predict prognosis and to provide guidance for optimal therapeutic decision-making in patients with gallbladder adenocarcinoma. The expressions of p16, p21, p27, p53, p63, cyclin D1, bcl-2 and bcl-6 were examined in a tissue microarray constructed from 96 cases of gallbladder adenocarcinoma by immunohistochemistry and correlated with clinicopathologic prognostic factors. Expression of p16 was correlated with a low pT stage, adenoma background and good prognosis. Cases with p63 expression showed a higher T stage, more frequent perineural invasion and poor prognosis when compared to cases without p63 expression. Over-expression of p53 or loss of p53 was associated with poor tumor differentiation, frequent distant metastasis and low disease-specific survival rate. The expressions of p21, p27, bcl-2, bcl-6 and cyclin D1 were not significant prognostic factors for gallbladder adenocarcinoma. These results indicate that p16, p63 and p53 can be used as prognostic markers in gallbladder adenocarcinoma; especially p53 and p63 as poor prognostic markers and p16 as a favorable prognostic marker.","Source":"PubMed","category":"HUMAN","training_data":"Expression of cell cycle-related proteins, p16, p53 and p63 as important prognostic markers in gallbladder adenocarcinoma Gallbladder cancer, the most common biliary tract malignancy, is a highly malignant neoplasm. In the present work, we have analyzed the significance of cell cycle-related proteins to predict prognosis and to provide guidance for optimal therapeutic decision-making in patients with gallbladder adenocarcinoma. The expressions of p16, p21, p27, p53, p63, cyclin D1, bcl-2 and bcl-6 were examined in a tissue microarray constructed from 96 cases of gallbladder adenocarcinoma by immunohistochemistry and correlated with clinicopathologic prognostic factors. Expression of p16 was correlated with a low pT stage, adenoma background and good prognosis. Cases with p63 expression showed a higher T stage, more frequent perineural invasion and poor prognosis when compared to cases without p63 expression. Over-expression of p53 or loss of p53 was associated with poor tumor differentiation, frequent distant metastasis and low disease-specific survival rate. The expressions of p21, p27, bcl-2, bcl-6 and cyclin D1 were not significant prognostic factors for gallbladder adenocarcinoma. These results indicate that p16, p63 and p53 can be used as prognostic markers in gallbladder adenocarcinoma; especially p53 and p63 as poor prognostic markers and p16 as a favorable prognostic marker. PubMed","prediction_labels":"HUMAN"},{"cleaned":"first results swedish national pancreatic periampullary cancer registry background despite improvements therapy regimens past decades overall survival rates pancreatic periampullary cancer poor specific cancer registries set various nations regional differences enable larger prospective trials aim study describe swedish register including possibilities improve diagnostic work ups treatment follow means register methods since 2010 patients pancreatic periampullary cancer including also patients undergone pancreatic surgery due premalignant benign lesions registered swedish national periampullary pancreatic cancer registry results total 9887 patients listed registry 8207 malignant periampullary cancer approximately one third 3282 patients resections performed including benign premalignant resections 30 day 90 day mortality pancreatoduodenectomy 1 5 3 5 respectively overall 3 year survival resected pancreatic ductal adenocarcinoma 35 regional variations decreased studied period still exist conclusion results swedish national registry satisfactory comparable international standards trends time show increasing resection rates improved results better collaboration openness within pancreatic surgeons important side effect pubmed","probabilities":0.9799733,"Title":"First results from the Swedish National Pancreatic and Periampullary Cancer Registry","Abstract":"BACKGROUND: Despite improvements in therapy regimens over the past decades, overall survival rates for pancreatic and periampullary cancer are poor. Specific cancer registries are set up in various nations to regional differences and to enable larger prospective trials. The aim of this study was to describe the Swedish register, including possibilities to improve diagnostic work-ups, treatment, and follow-up by means of the register. METHODS: Since 2010, all patients with pancreatic and periampullary cancer (including also patients who have undergone pancreatic surgery due to premalignant or benign lesions) have been registered in the Swedish National Periampullary and Pancreatic Cancer registry. RESULTS: In total 9887 patients are listed in the registry; 8207 of those have malignant periampullary cancer. Approximately one-third (3282 patients) have had resections performed, including benign/premalignant resections. 30-day and 90-day mortality after pancreatoduodenectomy is 1.5% and 3.5%, respectively. The overall 3-year survival for resected pancreatic ductal adenocarcinoma is 35%. Regional variations decreased over the studied period, but still exist. CONCLUSION: Results from the Swedish National Registry are satisfactory and comparable to international standards. Trends over time show increasing resection rates and some improved results. Better collaboration and openness within pancreatic surgeons is an important side effect.","Source":"PubMed","category":"HUMAN","training_data":"First results from the Swedish National Pancreatic and Periampullary Cancer Registry BACKGROUND: Despite improvements in therapy regimens over the past decades, overall survival rates for pancreatic and periampullary cancer are poor. Specific cancer registries are set up in various nations to regional differences and to enable larger prospective trials. The aim of this study was to describe the Swedish register, including possibilities to improve diagnostic work-ups, treatment, and follow-up by means of the register. METHODS: Since 2010, all patients with pancreatic and periampullary cancer (including also patients who have undergone pancreatic surgery due to premalignant or benign lesions) have been registered in the Swedish National Periampullary and Pancreatic Cancer registry. RESULTS: In total 9887 patients are listed in the registry; 8207 of those have malignant periampullary cancer. Approximately one-third (3282 patients) have had resections performed, including benign/premalignant resections. 30-day and 90-day mortality after pancreatoduodenectomy is 1.5% and 3.5%, respectively. The overall 3-year survival for resected pancreatic ductal adenocarcinoma is 35%. Regional variations decreased over the studied period, but still exist. CONCLUSION: Results from the Swedish National Registry are satisfactory and comparable to international standards. Trends over time show increasing resection rates and some improved results. Better collaboration and openness within pancreatic surgeons is an important side effect. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value lymph node ratio resection periampullary carcinomas background data indicated lymph node ratio lnr may better prognostic indicator lymph node status pancreatic cancer objectives analyse value lnr patients undergoing resection periampullary carcinomas methods cut value 0 2 assigned lnr accordance published studies impact histopathological factors including lnr analysed using kaplan meier cox regression methods results total 551 patients undergoing resection january 2000 december 2010 analysed median lymph node yield 15 198 34 patients lnr 0 2 patients lnr 0 2 median overall survival os 18 versus 33 months patients lnr 0 2 p 0 001 univariate analysis demonstrated lnr 0 2 n stage vascular perineural invasion grade resection margin status significantly associated os multivariate analysis lnr 0 2 vascular perineural invasion margin positivity remained significant n1 disease lnr able distinguish survival patients similar lymph node burden correlated aggressive tumour pathological variables conclusion lnr 0 2 lymph note status independent prognostic factor os indicating lnr utilized outcome stratification pubmed","probabilities":0.9799733,"Title":"Prognostic value of the lymph node ratio after resection of periampullary carcinomas","Abstract":"BACKGROUND: Data have indicated that the lymph node ratio (LNR) may be a better prognostic indicator than lymph node status in pancreatic cancer. OBJECTIVES: To analyse the value of the LNR in patients undergoing resection for periampullary carcinomas. METHODS: A cut off value of 0.2 was assigned to the LNR in accordance with published studies. The impact of histopathological factors including a LNR was analysed using Kaplan-Meier and Cox regression methods. RESULTS: In total, 551 patients undergoing a resection (January 2000 to December 2010) were analysed. The median lymph node yield was 15, and 198 (34%) patients had a LNR > 0.2. In patients with a LNR of > 0.2, the median overall survival (OS) was 18 versus 33 months in patients with an LNR < 0.2 (P < 0.001). Univariate analysis demonstrated a LNR > 0.2, T and N stage, vascular or perineural invasion, grade and resection margin status to be significantly associated with OS. On multivariate analysis, only a LNR > 0.2, vascular or perineural invasion and margin positivity remained significant. In N1 disease, a LNR was able to distinguish survival in patients with a similar lymph node burden, and correlated with more aggressive tumour pathological variables. CONCLUSION: A LNR > 0.2, and not lymph note status, is an independent prognostic factor for OS indicating the LNR should be utilized in outcome stratification.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic value of the lymph node ratio after resection of periampullary carcinomas BACKGROUND: Data have indicated that the lymph node ratio (LNR) may be a better prognostic indicator than lymph node status in pancreatic cancer. OBJECTIVES: To analyse the value of the LNR in patients undergoing resection for periampullary carcinomas. METHODS: A cut off value of 0.2 was assigned to the LNR in accordance with published studies. The impact of histopathological factors including a LNR was analysed using Kaplan-Meier and Cox regression methods. RESULTS: In total, 551 patients undergoing a resection (January 2000 to December 2010) were analysed. The median lymph node yield was 15, and 198 (34%) patients had a LNR > 0.2. In patients with a LNR of > 0.2, the median overall survival (OS) was 18 versus 33 months in patients with an LNR < 0.2 (P < 0.001). Univariate analysis demonstrated a LNR > 0.2, T and N stage, vascular or perineural invasion, grade and resection margin status to be significantly associated with OS. On multivariate analysis, only a LNR > 0.2, vascular or perineural invasion and margin positivity remained significant. In N1 disease, a LNR was able to distinguish survival in patients with a similar lymph node burden, and correlated with more aggressive tumour pathological variables. CONCLUSION: A LNR > 0.2, and not lymph note status, is an independent prognostic factor for OS indicating the LNR should be utilized in outcome stratification. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical resection bismuth type iv perihilar cholangiocarcinoma background bismuth type iv perihilar cholangiocarcinoma traditionally categorized unresectable disease aim study review experience resection based strategy patients type iv perihilar cholangiocarcinoma methods medical records consecutive patients diagnosis type iv perihilar cholangiocarcinoma 2006 2015 reviewed retrospectively primary outcomes assessed surgical results long term survival results 332 patients type iv tumour 216 65 1 per cent underwent resection left hepatic trisectionectomy common procedure 112 patients combined vascular resection performed 131 patients median duration operation 607 range 356 1045 min blood loss 1357 209 10 349 ml complications clavien dindo grade iii developed 90 patients 41 7 per cent four 1 9 per cent died complications within 90 days survival rates better 216 patients whose tumours resected 116 patients unresected tumours 32 8 versus 1 5 per cent 5 years p 0 001 patients pn0 m0 disease resection favourable 5 year survival rate 53 per cent percutaneous transhepatic biliary drainage blood transfusion lymph node metastasis distant metastasis identified independent negative prognostic factors survival conclusion although resection type iv tumour technically demanding high morbidity performed low mortality offers better survival probability selected patients pubmed","probabilities":0.9799733,"Title":"Surgical resection for Bismuth type IV perihilar cholangiocarcinoma","Abstract":"BACKGROUND: Bismuth type IV perihilar cholangiocarcinoma has traditionally been categorized as unresectable disease. The aim of this study was to review experience with a resection-based strategy in patients who have type IV perihilar cholangiocarcinoma. METHODS: Medical records of consecutive patients with a diagnosis of type IV perihilar cholangiocarcinoma between 2006 and 2015 were reviewed retrospectively. Primary outcomes assessed were surgical results and long-term survival. RESULTS: Of the 332 patients with type IV tumour, 216 (65·1 per cent) underwent resection. Left hepatic trisectionectomy was the most common procedure (112 patients). Combined vascular resection was performed in 131 patients. Median duration of operation was 607 (range 356-1045) min, and blood loss was 1357 (209-10 349) ml. Complications of Clavien-Dindo grade III or more developed in 90 patients (41·7 per cent) and four (1·9 per cent) died from complications within 90 days. Survival rates were better for the 216 patients whose tumours were resected than for the 116 patients with unresected tumours (32·8 versus 1·5 per cent at 5 years; P < 0·001). Patients with pN0 M0 disease after resection had a favourable 5-year survival rate of 53 per cent. Percutaneous transhepatic biliary drainage, blood transfusion, lymph node metastasis and distant metastasis were identified as independent negative prognostic factors for survival. CONCLUSION: Although resection for type IV tumour is technically demanding with high morbidity, it can be performed with low mortality and offers better survival probability in selected patients.","Source":"PubMed","category":"HUMAN","training_data":"Surgical resection for Bismuth type IV perihilar cholangiocarcinoma BACKGROUND: Bismuth type IV perihilar cholangiocarcinoma has traditionally been categorized as unresectable disease. The aim of this study was to review experience with a resection-based strategy in patients who have type IV perihilar cholangiocarcinoma. METHODS: Medical records of consecutive patients with a diagnosis of type IV perihilar cholangiocarcinoma between 2006 and 2015 were reviewed retrospectively. Primary outcomes assessed were surgical results and long-term survival. RESULTS: Of the 332 patients with type IV tumour, 216 (65·1 per cent) underwent resection. Left hepatic trisectionectomy was the most common procedure (112 patients). Combined vascular resection was performed in 131 patients. Median duration of operation was 607 (range 356-1045) min, and blood loss was 1357 (209-10 349) ml. Complications of Clavien-Dindo grade III or more developed in 90 patients (41·7 per cent) and four (1·9 per cent) died from complications within 90 days. Survival rates were better for the 216 patients whose tumours were resected than for the 116 patients with unresected tumours (32·8 versus 1·5 per cent at 5 years; P < 0·001). Patients with pN0 M0 disease after resection had a favourable 5-year survival rate of 53 per cent. Percutaneous transhepatic biliary drainage, blood transfusion, lymph node metastasis and distant metastasis were identified as independent negative prognostic factors for survival. CONCLUSION: Although resection for type IV tumour is technically demanding with high morbidity, it can be performed with low mortality and offers better survival probability in selected patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"predictive value staging systems inflammation scores patients combined hepatocellular cholangiocarcinoma surgical resection retrospective study background combined hepatocellular cholangiocarcinoma chcc cc rare form primary liver tumor specific staging system predicting survival patients chcc cc available aim present study evaluate ability staging systems inflammation based scores predict overall survival os progression free survival pfs patients chcc cc surgical resection methods data 99 patients chcc cc surgical resection june 2000 january 2017 retrospectively collected patients allocated hcc hepatocellular carcinoma dominant ihd group icc intrahepatic cholangiocarcinoma dominant iid group based radiological characteristics similarly patients also divided hcc dominant phd group icc dominant pid group based pathological characteristics univariate multivariate analyses performed identify variables associated os pfs prognostic value staging systems inflammation based scores analyzed compared using receiver operating characteristic roc curves results 1 2 3 year os rates 82 6 66 3 59 6 respectively 1 2 3 year pfs rates 52 2 38 1 31 5 respectively independent prognostic factors identified multivariate analyses included hcc tnm staging system tumor diameter os pfs analyses hcc tnm staging system displayed higher area roc curve auc values staging systems inflammation based scores conclusions hcc tnm staging system able adequately predict prognosis patients chcc cc surgical resection especially patients hcc dominant characteristics clinical practice pubmed","probabilities":0.9799733,"Title":"The Predictive Value of Staging Systems and Inflammation Scores for Patients with Combined Hepatocellular Cholangiocarcinoma After Surgical Resection: a Retrospective Study","Abstract":"BACKGROUND: Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare form of primary liver tumor. A specific staging system for predicting survival in patients with cHCC-CC is not available. The aim of the present study was to evaluate the ability of staging systems and inflammation-based scores to predict overall survival (OS) and progression-free survival (PFS) of patients with cHCC-CC after surgical resection. METHODS: The data from 99 patients with cHCC-CC after surgical resection from June 2000 and January 2017 were retrospectively collected. Patients were allocated into HCC (hepatocellular carcinoma)-dominant (IHD) group and ICC (intrahepatic cholangiocarcinoma)-dominant (IID) group based on radiological characteristics. Similarly, patients were also divided into HCC-dominant (PHD) group and ICC-dominant (PID) group based on pathological characteristics. Univariate and multivariate analyses were performed to identify variables associated with OS and PFS. The prognostic value of staging systems and inflammation-based scores were analyzed and compared using receiver operating characteristic (ROC) curves. RESULTS: The 1-, 2-, and 3-year OS rates were 82.6, 66.3, and 59.6%, respectively. The 1-, 2-, and 3-year PFS rates were 52.2, 38.1, and 31.5%, respectively. Independent prognostic factors identified by multivariate analyses included HCC-TNM staging system and tumor diameter both for OS and PFS analyses. HCC-TNM staging system displayed higher area under ROC curve (AUC) values than the other staging systems or inflammation-based scores. CONCLUSIONS: HCC-TNM staging system was able to adequately predict prognosis of patients with cHCC-CC after surgical resection, especially for patients with HCC-dominant characteristics in clinical practice.","Source":"PubMed","category":"HUMAN","training_data":"The Predictive Value of Staging Systems and Inflammation Scores for Patients with Combined Hepatocellular Cholangiocarcinoma After Surgical Resection: a Retrospective Study BACKGROUND: Combined hepatocellular cholangiocarcinoma (cHCC-CC) is a rare form of primary liver tumor. A specific staging system for predicting survival in patients with cHCC-CC is not available. The aim of the present study was to evaluate the ability of staging systems and inflammation-based scores to predict overall survival (OS) and progression-free survival (PFS) of patients with cHCC-CC after surgical resection. METHODS: The data from 99 patients with cHCC-CC after surgical resection from June 2000 and January 2017 were retrospectively collected. Patients were allocated into HCC (hepatocellular carcinoma)-dominant (IHD) group and ICC (intrahepatic cholangiocarcinoma)-dominant (IID) group based on radiological characteristics. Similarly, patients were also divided into HCC-dominant (PHD) group and ICC-dominant (PID) group based on pathological characteristics. Univariate and multivariate analyses were performed to identify variables associated with OS and PFS. The prognostic value of staging systems and inflammation-based scores were analyzed and compared using receiver operating characteristic (ROC) curves. RESULTS: The 1-, 2-, and 3-year OS rates were 82.6, 66.3, and 59.6%, respectively. The 1-, 2-, and 3-year PFS rates were 52.2, 38.1, and 31.5%, respectively. Independent prognostic factors identified by multivariate analyses included HCC-TNM staging system and tumor diameter both for OS and PFS analyses. HCC-TNM staging system displayed higher area under ROC curve (AUC) values than the other staging systems or inflammation-based scores. CONCLUSIONS: HCC-TNM staging system was able to adequately predict prognosis of patients with cHCC-CC after surgical resection, especially for patients with HCC-dominant characteristics in clinical practice. PubMed","prediction_labels":"HUMAN"},{"cleaned":"integrin av 6 predicts poor prognosis promotes resistance cisplatin hilar cholangiocarcinoma objective integrin v 6 associated extremely aggressive cancer phenotype however little known clinicopathological significance prognostic value integrin v 6 human hilar cholangiocarcinoma methods present study bioinformatics analysis demonstrated significant increase integrin 6 gene expression cholangiocarcinoma tissues compared non tumorous tissues validated clinical samples rt qpcr western blotting analyses integrin v 6 observed expressed 48 6 tumors expression related poor tumor differentiation p 0 002 lymph node metastasis p 0 001 advanced tnm stage p 0 001 furthermore patients v 6 positive showed significantly shorter overall survival period v 6 negative p 0 004 multivariate analysis confirmed integrin v 6 independent prognostic factor p 0 002 addition loss gain function assays showed integrin v 6 played important role colony formation also protected cholangiocarcinoma cells cisplatin induced growth inhibition apoptosis erk mapk signaling pathway involved integrin v 6 mediated resistance cholangiocarcinoma cells cisplatin conclusions taken together present findings revealed integrin v 6 serve potential prognostic predictor contribute cisplatin resistance might prove promising target candidate clinical intervention human hilar cholangiocarcinoma google scholar","probabilities":0.8684211,"Title":"Integrin Avß6 Predicts Poor Prognosis And Promotes Resistance To Cisplatin In Hilar Cholangiocarcinoma","Abstract":"Objective\nIntegrin αvβ6 is associated with an extremely aggressive cancer phenotype. However, little is known about the clinicopathological significance and prognostic value of integrin αvβ6 in human hilar cholangiocarcinoma.\nMethods\nIn the present study, bioinformatics analysis demonstrated a significant increase of integrin β6 gene expression in cholangiocarcinoma tissues compared to non-tumorous tissues, which was further validated in clinical samples through RT-qPCR and western blotting analyses. Integrin αvβ6 was observed to be expressed in 48.6% of tumors, and its expression was related to a poor tumor differentiation (p = 0.002), lymph node metastasis (p<0.001) and advanced TNM stage (p=0.001). Furthermore, patients who were αvβ6-positive showed a significantly shorter overall survival period than those who were αvβ6-negative (p=0.004). Multivariate analysis confirmed that integrin αvβ6 was an independent prognostic factor (p=0.002). In addition, loss- and gain-of-function assays showed integrin αvβ6 not only played an important role in colony formation, but also protected cholangiocarcinoma cells from cisplatin-induced growth inhibition and apoptosis. ERK/MAPK signaling pathway was involved in integrin αvβ6-mediated resistance of cholangiocarcinoma cells to cisplatin.\nConclusions\nTaken together, the present findings revealed that integrin αvβ6 could serve as a potential prognostic predictor and contribute to cisplatin resistance, which might prove to be a promising target candidate for the clinical intervention of human hilar cholangiocarcinoma.","Source":"Google Scholar","category":"HUMAN","training_data":"Integrin Avß6 Predicts Poor Prognosis And Promotes Resistance To Cisplatin In Hilar Cholangiocarcinoma Objective\nIntegrin αvβ6 is associated with an extremely aggressive cancer phenotype. However, little is known about the clinicopathological significance and prognostic value of integrin αvβ6 in human hilar cholangiocarcinoma.\nMethods\nIn the present study, bioinformatics analysis demonstrated a significant increase of integrin β6 gene expression in cholangiocarcinoma tissues compared to non-tumorous tissues, which was further validated in clinical samples through RT-qPCR and western blotting analyses. Integrin αvβ6 was observed to be expressed in 48.6% of tumors, and its expression was related to a poor tumor differentiation (p = 0.002), lymph node metastasis (p<0.001) and advanced TNM stage (p=0.001). Furthermore, patients who were αvβ6-positive showed a significantly shorter overall survival period than those who were αvβ6-negative (p=0.004). Multivariate analysis confirmed that integrin αvβ6 was an independent prognostic factor (p=0.002). In addition, loss- and gain-of-function assays showed integrin αvβ6 not only played an important role in colony formation, but also protected cholangiocarcinoma cells from cisplatin-induced growth inhibition and apoptosis. ERK/MAPK signaling pathway was involved in integrin αvβ6-mediated resistance of cholangiocarcinoma cells to cisplatin.\nConclusions\nTaken together, the present findings revealed that integrin αvβ6 could serve as a potential prognostic predictor and contribute to cisplatin resistance, which might prove to be a promising target candidate for the clinical intervention of human hilar cholangiocarcinoma. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"extension hepatic resection ameliorates survival patients type iiia iiib klatskin tumors despite surgical complications background major hepatectomies hilar cholangiocarcinoma hc associated high rates morbidity mortality aimed evaluate surgical complications related extended hepatectomies hc type iii iv according bismuth corlette classification influence patients long term survival methods files patients major hepatectomy hc postoperative complications retrospectively reviewed patients complete postoperative follow taken account study postoperative morbidity mortality length hospital stay los well overall survival os disease free survival dfs recorded results five patients found respond inclusion criteria three required re operation one hospital death two patients still alive two died tumor recurrence dfs 36 49 months respectively actuarial mean os group 30 months actuarial dfs 26 months conclusions patients hc extensive resections bring clearly benefit terms survival even though increase postoperative morbidity mortality however postoperative complications managed susccesfully interfere long term survival pubmed","probabilities":0.9799733,"Title":"Extension of Hepatic Resection Ameliorates Survival in Patients with Type IIIa or IIIb Klatskin Tumors Despite Surgical Complications","Abstract":"Background: Major hepatectomies for hilar cholangiocarcinoma (HC) are associated with high rates of morbidity and mortality. We aimed to evaluate how and if surgical complications related to extended hepatectomies for HC type III and IV according to Bismuth-Corlette classification influence patients long-term survival. Methods: The files of all patients with major hepatectomy for HC and postoperative complications were retrospectively reviewed. Only patients with a complete postoperative follow up have be taken into account for the study. Postoperative morbidity and mortality, length of hospital stay (LOS) as well as overall survival (OS) and disease free survival (DFS) were recorded. Results: Five patients have been found to respond to all inclusion criteria. Three of them required re-operation with one in hospital death. Two patients are still alive and two other died because of the tumor recurrence with a DFS of 36 and 49 months respectively. The actuarial mean OS for the group was 30 months and the actuarial DFS was 26 months. Conclusions: In patients with HC, extensive resections bring a clearly benefit in terms of survival, even though there is an increase in postoperative morbidity and mortality. However, postoperative complications, if managed susccesfully do not interfere with the long-term survival.","Source":"PubMed","category":"HUMAN","training_data":"Extension of Hepatic Resection Ameliorates Survival in Patients with Type IIIa or IIIb Klatskin Tumors Despite Surgical Complications Background: Major hepatectomies for hilar cholangiocarcinoma (HC) are associated with high rates of morbidity and mortality. We aimed to evaluate how and if surgical complications related to extended hepatectomies for HC type III and IV according to Bismuth-Corlette classification influence patients long-term survival. Methods: The files of all patients with major hepatectomy for HC and postoperative complications were retrospectively reviewed. Only patients with a complete postoperative follow up have be taken into account for the study. Postoperative morbidity and mortality, length of hospital stay (LOS) as well as overall survival (OS) and disease free survival (DFS) were recorded. Results: Five patients have been found to respond to all inclusion criteria. Three of them required re-operation with one in hospital death. Two patients are still alive and two other died because of the tumor recurrence with a DFS of 36 and 49 months respectively. The actuarial mean OS for the group was 30 months and the actuarial DFS was 26 months. Conclusions: In patients with HC, extensive resections bring a clearly benefit in terms of survival, even though there is an increase in postoperative morbidity and mortality. However, postoperative complications, if managed susccesfully do not interfere with the long-term survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"improvement perioperative long term outcome surgical treatment hilar cholangiocarcinoma results italian multicenter analysis 440 patients objective evaluate improvements operative long term results following surgery hilar cholangiocarcinoma design retrospective multicenter study including 17 italian hepatobiliary surgery units patients total 440 patients underwent resection hilar cholangiocarcinoma january 1 1992 december 31 2007 main outcome measures postoperative mortality morbidity overall survival disease free survival results postoperative mortality morbidity liver resection 10 1 47 6 respectively multivariate logistic regression extent resection right right extended hepatectomy intraoperative blood transfusion independent predictors postoperative mortality p 03 p 006 respectively patients jaundice mortality also higher without preoperative biliary drainage biliary drainage 14 3 vs 10 7 study period increasingly aggressive approach frequent caudate lobectomies vascular resections resections advanced tumors stage 3 greater tumors poor differentiation despite aggressive approach blood transfusion rate decreased 81 0 53 2 mortality slightly decreased 13 6 10 8 median overall survival significantly increased 16 30 months p 05 multivariate analysis r1 resection lymph node metastases stage 3 greater independently predicted overall disease free survival conclusions surgery hilar cholangiocarcinoma improved decreased operative risk despite aggressive surgical policy long term survival liver resection also increased despite inclusion cases advanced hilar cholangiocarcinoma preoperative biliary drainage safe strategy right right extended hepatectomy patients jaundice pathologic factors independently predicted overall disease free survival multivariate analysis pubmed","probabilities":0.9799733,"Title":"Improvement in perioperative and long-term outcome after surgical treatment of hilar cholangiocarcinoma: results of an Italian multicenter analysis of 440 patients","Abstract":"OBJECTIVE: To evaluate improvements in operative and long-term results following surgery for hilar cholangiocarcinoma. DESIGN: Retrospective multicenter study including 17 Italian hepatobiliary surgery units. PATIENTS: A total of 440 patients who underwent resection for hilar cholangiocarcinoma from January 1, 1992, through December 31, 2007. MAIN OUTCOME MEASURES: Postoperative mortality, morbidity, overall survival, and disease-free survival. RESULTS: Postoperative mortality and morbidity after liver resection were 10.1% and 47.6%, respectively. At multivariate logistic regression, extent of resection (right or right extended hepatectomy) and intraoperative blood transfusion were independent predictors of postoperative mortality (P = .03 and P = .006, respectively); in patients with jaundice, mortality was also higher without preoperative biliary drainage than with biliary drainage (14.3% vs 10.7%). During the study period, there was an increasingly aggressive approach, with more frequent caudate lobectomies, vascular resections, and resections for advanced tumors (T stage of 3 or greater and tumors with poor differentiation). Despite the aggressive approach, the blood transfusion rate decreased from 81.0% to 53.2%, and mortality slightly decreased from 13.6% to 10.8%. Median overall survival significantly increased from 16 to 30 months (P = .05). At multivariate analysis, R1 resection, lymph node metastases, and T stage of 3 or greater independently predicted overall and disease-free survival. CONCLUSIONS: Surgery for hilar cholangiocarcinoma has improved with decreased operative risk despite a more aggressive surgical policy. Long-term survival after liver resection has also increased, despite the inclusion of cases with more advanced hilar cholangiocarcinoma. Preoperative biliary drainage was a safe strategy before right or right extended hepatectomy in patients with jaundice. Pathologic factors independently predicted overall and disease-free survival at multivariate analysis.","Source":"PubMed","category":"HUMAN","training_data":"Improvement in perioperative and long-term outcome after surgical treatment of hilar cholangiocarcinoma: results of an Italian multicenter analysis of 440 patients OBJECTIVE: To evaluate improvements in operative and long-term results following surgery for hilar cholangiocarcinoma. DESIGN: Retrospective multicenter study including 17 Italian hepatobiliary surgery units. PATIENTS: A total of 440 patients who underwent resection for hilar cholangiocarcinoma from January 1, 1992, through December 31, 2007. MAIN OUTCOME MEASURES: Postoperative mortality, morbidity, overall survival, and disease-free survival. RESULTS: Postoperative mortality and morbidity after liver resection were 10.1% and 47.6%, respectively. At multivariate logistic regression, extent of resection (right or right extended hepatectomy) and intraoperative blood transfusion were independent predictors of postoperative mortality (P = .03 and P = .006, respectively); in patients with jaundice, mortality was also higher without preoperative biliary drainage than with biliary drainage (14.3% vs 10.7%). During the study period, there was an increasingly aggressive approach, with more frequent caudate lobectomies, vascular resections, and resections for advanced tumors (T stage of 3 or greater and tumors with poor differentiation). Despite the aggressive approach, the blood transfusion rate decreased from 81.0% to 53.2%, and mortality slightly decreased from 13.6% to 10.8%. Median overall survival significantly increased from 16 to 30 months (P = .05). At multivariate analysis, R1 resection, lymph node metastases, and T stage of 3 or greater independently predicted overall and disease-free survival. CONCLUSIONS: Surgery for hilar cholangiocarcinoma has improved with decreased operative risk despite a more aggressive surgical policy. Long-term survival after liver resection has also increased, despite the inclusion of cases with more advanced hilar cholangiocarcinoma. Preoperative biliary drainage was a safe strategy before right or right extended hepatectomy in patients with jaundice. Pathologic factors independently predicted overall and disease-free survival at multivariate analysis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"molecular pathways potential biomarkers gallbladder cancer comprehensive review common malignancy biliary tract gallbladder cancer gbc often dismal prognosis aggressive nature tumor delayed diagnosis advanced stages disease lack effective treatment options factors contribute poor outcome early detection accurate assessment disease burden critical optimize management improve long term survival well identify patients adjuvant therapy clinical trials recent advances understanding molecular pathogenesis gbc several specific diagnostic biomarkers proposed diagnostic prognostic importance indeed identification novel diagnostic prognostic markers important role early diagnosis development targeted therapies among patients gbc next generation sequencing technology genomewide data analysis provided novel insight understanding molecular pathogenesis biliary tract cancers thereby identifying potential biomarkers clinical use herein review available gbc biomarkers potential clinical implications management gbc pubmed","probabilities":0.9799733,"Title":"Molecular pathways and potential biomarkers in gallbladder cancer: A comprehensive review","Abstract":"The most common malignancy of the biliary tract, gallbladder cancer (GBC) often has a dismal prognosis. The aggressive nature of the tumor, delayed diagnosis at advanced stages of the disease, and lack of effective treatment options are some of the factors that contribute to a poor outcome. Early detection and accurate assessment of disease burden is critical to optimize management and improve long-term survival, as well as identify patients for adjuvant therapy and clinical trials. With recent advances in the understanding of the molecular pathogenesis of GBC, several specific diagnostic and biomarkers have been proposed as being of diagnostic and prognostic importance. Indeed, identification of novel diagnostic and prognostic markers has an important role in early diagnosis and development of targeted therapies among patients with GBC. Next-generation sequencing technology and genomewide data analysis have provided novel insight into understanding the molecular pathogenesis of biliary tract cancers, thereby identifying potential biomarkers for clinical use. We herein review available GBC biomarkers and the potential clinical implications in the management of GBC.","Source":"PubMed","category":"HUMAN","training_data":"Molecular pathways and potential biomarkers in gallbladder cancer: A comprehensive review The most common malignancy of the biliary tract, gallbladder cancer (GBC) often has a dismal prognosis. The aggressive nature of the tumor, delayed diagnosis at advanced stages of the disease, and lack of effective treatment options are some of the factors that contribute to a poor outcome. Early detection and accurate assessment of disease burden is critical to optimize management and improve long-term survival, as well as identify patients for adjuvant therapy and clinical trials. With recent advances in the understanding of the molecular pathogenesis of GBC, several specific diagnostic and biomarkers have been proposed as being of diagnostic and prognostic importance. Indeed, identification of novel diagnostic and prognostic markers has an important role in early diagnosis and development of targeted therapies among patients with GBC. Next-generation sequencing technology and genomewide data analysis have provided novel insight into understanding the molecular pathogenesis of biliary tract cancers, thereby identifying potential biomarkers for clinical use. We herein review available GBC biomarkers and the potential clinical implications in the management of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"2 neu expression gall bladder adenocarcinoma quest potential therapeutic target background gall bladder carcinoma gbc aggressive malignancy high mortality aggressive course palliation available option objectives evaluate frequency 2 neu overexpression gbc seek correlation conventional clinicopathological parameters survival methods immunohistochemistry ihc performed 200 cases gbc 32 cases dysplasia 100 cases chronic cholecystitis fluorescent situ hybridization fish performed 30 randomly selected cases gbc validate ihc 2 neu overexpression ihc 3 fish amplification 2 2 correlated clinicopathological parameters chi square test p 0 05 considered significant survival analysis done log rank test kaplan meier analysis results 2 neu overexpression seen 14 28 200 gbc cases found dysplasia chronic cholecystitis majority cases grade 2 advanced stage however statistically significant lower mean survival 2 neu positive group compared 2 neu negative group 17 1 2 3 month versus 67 6 8 5 month respectively observed concordance ihc fish seen 18 19 cases conclusion study delineates subset gbc patients 2 neu overexpression targeted therapy offer survival benefit stn","probabilities":0.9799733,"Title":"Her-2/Neu Over Expression In Gall Bladder Adenocarcinoma: A Quest For Potential Therapeutic Target","Abstract":"Background: Gall bladder carcinoma (GBC) is an aggressive malignancy with high mortality and aggressive course, with palliation as the only available option. \r\n\r\n Objectives: To evaluate frequency of HER-2/neu overexpression in GBC and to seek its correlation, if any with conventional clinicopathological parameters and survival. \r\n\r\n Methods: Immunohistochemistry (IHC) was performed on 200 cases of GBC, 32 cases of dysplasia, and 100 cases of chronic cholecystitis. Fluorescent in situ hybridization (FISH) was performed on 30 randomly selected cases of GBC to validate IHC. HER-2/neu overexpression (IHC 3+/FISH amplification ≥2.2) was correlated with clinicopathological parameters by Chi-square test.P < 0.05 was considered significant. Survival analysis was done by log-rank test and Kaplan-Meier analysis. \r\n\r\n Results: HER-2/neu overexpression was seen in 14% (28/200) GBC cases but was not found in dysplasia and chronic cholecystitis. Majority of these cases were ≤grade 2 and in advanced stage, however this was not statistically significant. A lower mean survival in HER-2/neu positive group as compared to HER-2/neu negative group (17.1 ± 2.3 month versus 67.6 ± 8.5 month, respectively) was observed. Concordance between IHC and FISH was seen in 18/19 cases. \r\n\r\n Conclusion: This study delineates a subset of GBC patients with HER-2/neu overexpression, in whom targeted therapy can offer a survival benefit.","Source":"STN","category":"ANIMAL","training_data":"Her-2/Neu Over Expression In Gall Bladder Adenocarcinoma: A Quest For Potential Therapeutic Target Background: Gall bladder carcinoma (GBC) is an aggressive malignancy with high mortality and aggressive course, with palliation as the only available option. \r\n\r\n Objectives: To evaluate frequency of HER-2/neu overexpression in GBC and to seek its correlation, if any with conventional clinicopathological parameters and survival. \r\n\r\n Methods: Immunohistochemistry (IHC) was performed on 200 cases of GBC, 32 cases of dysplasia, and 100 cases of chronic cholecystitis. Fluorescent in situ hybridization (FISH) was performed on 30 randomly selected cases of GBC to validate IHC. HER-2/neu overexpression (IHC 3+/FISH amplification ≥2.2) was correlated with clinicopathological parameters by Chi-square test.P < 0.05 was considered significant. Survival analysis was done by log-rank test and Kaplan-Meier analysis. \r\n\r\n Results: HER-2/neu overexpression was seen in 14% (28/200) GBC cases but was not found in dysplasia and chronic cholecystitis. Majority of these cases were ≤grade 2 and in advanced stage, however this was not statistically significant. A lower mean survival in HER-2/neu positive group as compared to HER-2/neu negative group (17.1 ± 2.3 month versus 67.6 ± 8.5 month, respectively) was observed. Concordance between IHC and FISH was seen in 18/19 cases. \r\n\r\n Conclusion: This study delineates a subset of GBC patients with HER-2/neu overexpression, in whom targeted therapy can offer a survival benefit. STN","prediction_labels":"HUMAN"},{"cleaned":"outcomes diagnostic challenges posed incidental cholangiocarcinoma liver transplantation background liver transplantation presence cholangiocarcinoma cca generally carries poor prognosis however outcome patients found incidental cca icca explanted liver histology less clear evaluated outcomes icca liver transplant population methods retrospective search made transplantation histopathology databases patients fulfilling definition icca records including archived histopathologic slides retrieved analyzed results 1288 patients undergoing liver transplantation 20 year period 1988 2008 nine found icca 0 70 seven nine patients underwent liver transplantation primary sclerosing cholangitis three additional patients transplanted presumed hepatocellular carcinoma subsequently turned cca identified excluded survival analysis majority tumors early stage t2 five 55 6 positive biliary transection margins median follow 51 months five patients 55 6 developed recurrence cca median interval 25 8 months giving disease free survival 100 1 year 66 7 3 years three patients died recurrence median interval transplantation 25 months overall 3 year survival 66 7 conclusions patients found icca liver transplantation relatively poor prognosis prospective liver transplant recipients especially primary sclerosing cholangitis investigated rigorously exclude cca pubmed","probabilities":0.9799733,"Title":"Outcomes and diagnostic challenges posed by incidental cholangiocarcinoma after liver transplantation","Abstract":"BACKGROUND: Liver transplantation in the presence of cholangiocarcinoma (CCA) generally carries a poor prognosis. However, the outcome of patients found to have incidental CCA (iCCA) on explanted liver histology is less clear. We have evaluated the outcomes of iCCA in our liver transplant population. METHODS: A retrospective search was made of the transplantation and histopathology databases for patients fulfilling our definition for iCCA. All records, including archived histopathologic slides were retrieved and analyzed. RESULTS: Of 1288 patients undergoing liver transplantation over the 20-year period 1988-2008, nine were found to have iCCA (0.70%). Seven of the nine patients underwent liver transplantation for primary sclerosing cholangitis. Three additional patients who were transplanted for presumed hepatocellular carcinoma that subsequently turned out to be CCA were identified, but excluded from survival analysis. The majority of tumors were early stage (T2 or below), but five (55.6%) had positive biliary transection margins. Median follow-up was 51 months. Five patients (55.6%) developed recurrence of CCA after a median interval of 25.8 months, giving a disease-free survival of 100% at 1 year and 66.7% at 3 years. Three patients have died of recurrence, with a median interval from transplantation of 25 months. The overall 3-year survival was 66.7%. CONCLUSIONS: Patients found to have iCCA after liver transplantation have a relatively poor prognosis. Prospective liver transplant recipients, especially those with primary sclerosing cholangitis, should be investigated rigorously to exclude CCA.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes and diagnostic challenges posed by incidental cholangiocarcinoma after liver transplantation BACKGROUND: Liver transplantation in the presence of cholangiocarcinoma (CCA) generally carries a poor prognosis. However, the outcome of patients found to have incidental CCA (iCCA) on explanted liver histology is less clear. We have evaluated the outcomes of iCCA in our liver transplant population. METHODS: A retrospective search was made of the transplantation and histopathology databases for patients fulfilling our definition for iCCA. All records, including archived histopathologic slides were retrieved and analyzed. RESULTS: Of 1288 patients undergoing liver transplantation over the 20-year period 1988-2008, nine were found to have iCCA (0.70%). Seven of the nine patients underwent liver transplantation for primary sclerosing cholangitis. Three additional patients who were transplanted for presumed hepatocellular carcinoma that subsequently turned out to be CCA were identified, but excluded from survival analysis. The majority of tumors were early stage (T2 or below), but five (55.6%) had positive biliary transection margins. Median follow-up was 51 months. Five patients (55.6%) developed recurrence of CCA after a median interval of 25.8 months, giving a disease-free survival of 100% at 1 year and 66.7% at 3 years. Three patients have died of recurrence, with a median interval from transplantation of 25 months. The overall 3-year survival was 66.7%. CONCLUSIONS: Patients found to have iCCA after liver transplantation have a relatively poor prognosis. Prospective liver transplant recipients, especially those with primary sclerosing cholangitis, should be investigated rigorously to exclude CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pancreatic resections patients aged 80 meta analysis systematic review objective aim study evaluate safety pancreatic resections patients 80 years older methods systematic search literature carried compared perioperative outcomes pancreatic resection patients 80 years older patients younger 80 years primary end points postoperative mortality morbidity secondary end points incidence postoperative pancreatic fistula delayed gastric emptying bile leak pneumonia postoperative infection cardiologic complications reoperation length hospital stay results nine studies found suitable meta analysis postoperative mortality morbidity significantly higher group 80 years older p 0 00001 p 0 003 respectively except patients differences preoperative comorbidities p 0 56 p 0 36 respectively postoperative cardiac complications significantly frequent patients 80 years older p 0 0001 length hospital stay significantly longer octogenarian patients p 0 008 conclusions patients 80 years older increased incidence postoperative mortality morbidity cardiac complications longer length hospital stay younger patients thus pancreatic resection recommended selected group patients 80 years older stn","probabilities":0.9799733,"Title":"Pancreatic Resections In Patients Aged 80 And Over: A Meta-Analysis And Systematic Review","Abstract":"Objective: The aim of this study was to evaluate the safety of pancreatic resections in patients 80 years or older. \r\n\r\n Methods: A systematic search of the literature was carried out that compared perioperative outcomes after pancreatic resection in patients 80 years or older with patients younger than 80 years. The primary end points were postoperative mortality and morbidity. The secondary end points were incidence of postoperative pancreatic fistula, delayed gastric emptying, bile leak, pneumonia, postoperative infection, cardiologic complications, reoperation, and length of hospital stay. \r\n\r\n Results: Nine studies were found to be suitable for the meta-analysis. The postoperative mortality and morbidity were significantly higher in the group 80 years or older (P < 0.00001 and P = 0.003, respectively) except for patients in whom there were no differences in preoperative comorbidities (P = 0.56 and P = 0.36, respectively). Postoperative cardiac complications were significantly more frequent in patients 80 years or older (P < 0.0001), and the length of hospital stay was significantly longer in octogenarian patients (P = 0.008). \r\n\r\n Conclusions: Patients 80 years or older have an increased incidence of postoperative mortality, morbidity, and cardiac complications and a longer length of hospital stay than do younger patients. Thus, pancreatic resection can be recommended only in a selected group of patients 80 years or older.","Source":"STN","category":"HUMAN","training_data":"Pancreatic Resections In Patients Aged 80 And Over: A Meta-Analysis And Systematic Review Objective: The aim of this study was to evaluate the safety of pancreatic resections in patients 80 years or older. \r\n\r\n Methods: A systematic search of the literature was carried out that compared perioperative outcomes after pancreatic resection in patients 80 years or older with patients younger than 80 years. The primary end points were postoperative mortality and morbidity. The secondary end points were incidence of postoperative pancreatic fistula, delayed gastric emptying, bile leak, pneumonia, postoperative infection, cardiologic complications, reoperation, and length of hospital stay. \r\n\r\n Results: Nine studies were found to be suitable for the meta-analysis. The postoperative mortality and morbidity were significantly higher in the group 80 years or older (P < 0.00001 and P = 0.003, respectively) except for patients in whom there were no differences in preoperative comorbidities (P = 0.56 and P = 0.36, respectively). Postoperative cardiac complications were significantly more frequent in patients 80 years or older (P < 0.0001), and the length of hospital stay was significantly longer in octogenarian patients (P = 0.008). \r\n\r\n Conclusions: Patients 80 years or older have an increased incidence of postoperative mortality, morbidity, and cardiac complications and a longer length of hospital stay than do younger patients. Thus, pancreatic resection can be recommended only in a selected group of patients 80 years or older. STN","prediction_labels":"HUMAN"},{"cleaned":"safety feasibility laparoscopic liver resection associated lymphadenectomy intrahepatic cholangiocarcinoma propensity score based case matched analysis single institution background intrahepatic cholangiocarcinoma icc still relatively uncommon indication laparoscopic surgery technical challenges related frequent need major hepatectomies necessity perform formal regional lymphadenectomy aim present case matched study compare laparoscopic open resections icc methods case matched retrospective analysis 20 consecutive patients undergone laparoscopic resection icc lps group compared 60 83 patients undergone open surgery open group institution groups matched ratio 1 3 using propensity scores based covariates representing relevant patient characteristics severity disease main endpoints short long term outcomes impact adequacy laparoscopic lymphadenectomy results groups well matched terms patient disease characteristics laparoscopic approach resulted less blood loss 200 vs 350 ml p 0 040 despite less extensive use pringle maneuver difference perioperative morbidity mortality rates however laparoscopic approach associated faster functional recovery median 3 vs 4 days p 0 050 mean follow 39 months disease free overall survivals 33 51 months respectively lps 36 63 respectively open group p ns number harvested nodes comparable groups conclusions compared open surgery laparoscopic resection icc feasible safe providing short term benefits without negatively affecting oncologic adequacy terms rate r0 resections depth margins long term overall disease free survivals laparoscopic regional lymphadenectomy technically possible object future focused studies pubmed","probabilities":0.9799733,"Title":"Safety and feasibility of laparoscopic liver resection with associated lymphadenectomy for intrahepatic cholangiocarcinoma: a propensity score-based case-matched analysis from a single institution","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is still a relatively uncommon indication for laparoscopic surgery because of technical challenges related to the frequent need for major hepatectomies and the necessity to perform formal regional lymphadenectomy. The aim of the present case-matched study was to compare laparoscopic and open resections for ICC. METHODS: In a case-matched retrospective analysis, 20 consecutive patients who had undergone laparoscopic resection for ICC (LPS group) were compared with 60 of 83 patients who had undergone open surgery (open group) in the same institution. The groups were matched in a ratio of 1:3 using propensity scores based on covariates representing relevant patient characteristics and severity of disease. The main endpoints were short- and long-term outcomes and impact and adequacy of laparoscopic lymphadenectomy. RESULTS: The groups were well matched in terms of patient and disease characteristics. The laparoscopic approach resulted in less blood loss (200 vs. 350 mL, p = 0.040) despite less extensive use of the Pringle maneuver. There was no difference in perioperative morbidity and mortality rates; however, the laparoscopic approach was associated with faster functional recovery (median 3 vs. 4 days, p = 0.050). After a mean follow-up of 39 months, disease-free and overall survivals were 33 and 51 months, respectively, for the LPS and 36 and 63, respectively, for the open group (p ns). The number of harvested nodes was comparable between groups. CONCLUSIONS: Compared with open surgery, laparoscopic resection of ICC is feasible and safe, providing short-term benefits without negatively affecting oncologic adequacy in terms of rate of R0 resections, depth of margins, and long-term overall and disease-free survivals. Laparoscopic regional lymphadenectomy is technically possible but should be the object of future focused studies.","Source":"PubMed","category":"HUMAN","training_data":"Safety and feasibility of laparoscopic liver resection with associated lymphadenectomy for intrahepatic cholangiocarcinoma: a propensity score-based case-matched analysis from a single institution BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is still a relatively uncommon indication for laparoscopic surgery because of technical challenges related to the frequent need for major hepatectomies and the necessity to perform formal regional lymphadenectomy. The aim of the present case-matched study was to compare laparoscopic and open resections for ICC. METHODS: In a case-matched retrospective analysis, 20 consecutive patients who had undergone laparoscopic resection for ICC (LPS group) were compared with 60 of 83 patients who had undergone open surgery (open group) in the same institution. The groups were matched in a ratio of 1:3 using propensity scores based on covariates representing relevant patient characteristics and severity of disease. The main endpoints were short- and long-term outcomes and impact and adequacy of laparoscopic lymphadenectomy. RESULTS: The groups were well matched in terms of patient and disease characteristics. The laparoscopic approach resulted in less blood loss (200 vs. 350 mL, p = 0.040) despite less extensive use of the Pringle maneuver. There was no difference in perioperative morbidity and mortality rates; however, the laparoscopic approach was associated with faster functional recovery (median 3 vs. 4 days, p = 0.050). After a mean follow-up of 39 months, disease-free and overall survivals were 33 and 51 months, respectively, for the LPS and 36 and 63, respectively, for the open group (p ns). The number of harvested nodes was comparable between groups. CONCLUSIONS: Compared with open surgery, laparoscopic resection of ICC is feasible and safe, providing short-term benefits without negatively affecting oncologic adequacy in terms of rate of R0 resections, depth of margins, and long-term overall and disease-free survivals. Laparoscopic regional lymphadenectomy is technically possible but should be the object of future focused studies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"key factors influencing prognosis relation gallbladder cancer introduction 5 year survival patients gallbladder cancer remains low however patients stratified prognostic categories based established factors n r status new concepts regarding prognostic significance lymph node disease importance residual gallbladder fossa disease gravity presentation jaundice reviewed addition number new prognostic factors proposed recent years considered methods pubmed searched gallbladder cancer builder date completion 2008 present total 1 490 articles screened 168 retrieved 40 articles specifically related prognosis form basis review discussion key factors prognostic significance remain n stage r0 resection residual disease either gallbladder fossa lymph nodes cystic duct margin dictates hepatectomy lymphadenectomy bile duct resection respectively adequate lymphadenectomy requires removal six nodes hepatectomy must sufficient achieve r0 subtleties regarding lymph node ratio significance pathological features dedifferentiation budding may hold value stratifying patients early stage disease require investigation pubmed","probabilities":0.9799733,"Title":"Key factors influencing prognosis in relation to gallbladder cancer","Abstract":"INTRODUCTION: The 5-year survival of patients with gallbladder cancer remains low. However, patients can be stratified into prognostic categories based on established factors such as T, N, and R status. New concepts regarding prognostic significance of lymph node disease, the importance of residual gallbladder fossa disease, and the gravity of presentation with jaundice are reviewed. In addition, a number of new prognostic factors proposed in recent years are considered. METHODS: PubMed was searched for \"gallbladder cancer\" with builder \"date-completion\" 2008 to present. A total of 1,490 articles were screened from which 168 were retrieved. From this, 40 articles specifically related to prognosis form the basis for this review. DISCUSSION: Key factors of prognostic significance remain T and N stage and R0 resection. Residual disease either in the gallbladder fossa, lymph nodes, or cystic duct margin dictates hepatectomy, lymphadenectomy and bile duct resection, respectively. Adequate lymphadenectomy requires removal of six nodes, and hepatectomy must be sufficient to achieve R0. Subtleties regarding lymph node ratio, significance of pathological features such as dedifferentiation, and budding may hold value for stratifying patients with early stage disease, but require further investigation.","Source":"PubMed","category":"HUMAN","training_data":"Key factors influencing prognosis in relation to gallbladder cancer INTRODUCTION: The 5-year survival of patients with gallbladder cancer remains low. However, patients can be stratified into prognostic categories based on established factors such as T, N, and R status. New concepts regarding prognostic significance of lymph node disease, the importance of residual gallbladder fossa disease, and the gravity of presentation with jaundice are reviewed. In addition, a number of new prognostic factors proposed in recent years are considered. METHODS: PubMed was searched for \"gallbladder cancer\" with builder \"date-completion\" 2008 to present. A total of 1,490 articles were screened from which 168 were retrieved. From this, 40 articles specifically related to prognosis form the basis for this review. DISCUSSION: Key factors of prognostic significance remain T and N stage and R0 resection. Residual disease either in the gallbladder fossa, lymph nodes, or cystic duct margin dictates hepatectomy, lymphadenectomy and bile duct resection, respectively. Adequate lymphadenectomy requires removal of six nodes, and hepatectomy must be sufficient to achieve R0. Subtleties regarding lymph node ratio, significance of pathological features such as dedifferentiation, and budding may hold value for stratifying patients with early stage disease, but require further investigation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence survival hepatic pancreatic biliary cancers england 1998 2007 introduction hepatic pancreatic biliary hpb cancers group diverse malignancies managed ideally specialist centres study describes recent patterns incidence survival hpb cancers england ten year period 1998 2007 methods data 99 379 english patients 50 656 males 48 723 females diagnosed hpb cancers 1998 2007 extracted national cancer data repository data divided six site specific cancer groups pancreas ampulla vater biliary tract primary liver gallbladder duodenum age standardised incidence rates per 100 000 european standard population asr e calculated six groups year diagnosis socioeconomic deprivation survival estimated using kaplan meier method results largest group pancreatic cancers 63 followed primary liver 14 biliary cancers 13 asr e highest pancreatic primary liver cancers whereas cancers gallbladder duodenum ampulla vater low incidence time incidence six groups remained relatively stable although primary liver cancer increased slightly males incidence rates higher males females groups except gallbladder cancer six groups higher incidence deprived quintiles overall survival poor hpb cancer groups conclusions hpb tumours uncommon associated poor long term survival reflecting late stage presentation incidence patterns suggest variable rates linked socioeconomic deprivation highlight male predominance sites except gallbladder identification high risk populations emphasised initiatives raise awareness facilitate earlier diagnosis stn","probabilities":0.9799733,"Title":"Incidence And Survival For Hepatic Pancreatic And Biliary Cancers In England Between 1998 And 2007","Abstract":"Introduction: Hepatic, pancreatic and biliary (HPB) cancers are a group of diverse malignancies managed ideally in specialist centres. This study describes recent patterns in the incidence and survival of HPB cancers in England over a ten year period (1998-2007). \r\n\r\n Methods: Data on 99,379 English patients (50,656 males; 48,723 females) diagnosed with HPB cancers between 1998 and 2007 were extracted from the National Cancer Data Repository. Data were divided into six site-specific cancer groups; pancreas, ampulla of Vater, biliary tract, primary liver, gallbladder and duodenum. Age-standardised incidence rates (per 100,000 European standard population, (ASR(E))) were calculated for each of the six groups by year of diagnosis and by socioeconomic deprivation. Survival was estimated using the Kaplan-Meier method. \r\n\r\n Results: The largest group was pancreatic cancers (63%), followed by primary liver (14%) and biliary cancers (13%). ASR(E) were highest for pancreatic and primary liver cancers whereas cancers of the gallbladder, duodenum and ampulla of Vater had a very low incidence. Over time the incidence of all six groups remained relatively stable, although primary liver cancer increased slightly in males. Incidence rates were higher in males than in females in all groups except gallbladder cancer, and all six groups had a higher incidence in the more deprived quintiles. Overall survival was poor in each of the HPB cancer groups. \r\n\r\n Conclusions: HPB tumours are uncommon and are associated with poor long term survival reflecting the late stage at presentation. Incidence patterns suggest variable rates linked to socioeconomic deprivation and highlight a male predominance in all sites except the gallbladder. Identification of high risk populations should be emphasised in initiatives to raise awareness and facilitate earlier diagnosis.","Source":"STN","category":"HUMAN","training_data":"Incidence And Survival For Hepatic Pancreatic And Biliary Cancers In England Between 1998 And 2007 Introduction: Hepatic, pancreatic and biliary (HPB) cancers are a group of diverse malignancies managed ideally in specialist centres. This study describes recent patterns in the incidence and survival of HPB cancers in England over a ten year period (1998-2007). \r\n\r\n Methods: Data on 99,379 English patients (50,656 males; 48,723 females) diagnosed with HPB cancers between 1998 and 2007 were extracted from the National Cancer Data Repository. Data were divided into six site-specific cancer groups; pancreas, ampulla of Vater, biliary tract, primary liver, gallbladder and duodenum. Age-standardised incidence rates (per 100,000 European standard population, (ASR(E))) were calculated for each of the six groups by year of diagnosis and by socioeconomic deprivation. Survival was estimated using the Kaplan-Meier method. \r\n\r\n Results: The largest group was pancreatic cancers (63%), followed by primary liver (14%) and biliary cancers (13%). ASR(E) were highest for pancreatic and primary liver cancers whereas cancers of the gallbladder, duodenum and ampulla of Vater had a very low incidence. Over time the incidence of all six groups remained relatively stable, although primary liver cancer increased slightly in males. Incidence rates were higher in males than in females in all groups except gallbladder cancer, and all six groups had a higher incidence in the more deprived quintiles. Overall survival was poor in each of the HPB cancer groups. \r\n\r\n Conclusions: HPB tumours are uncommon and are associated with poor long term survival reflecting the late stage at presentation. Incidence patterns suggest variable rates linked to socioeconomic deprivation and highlight a male predominance in all sites except the gallbladder. Identification of high risk populations should be emphasised in initiatives to raise awareness and facilitate earlier diagnosis. STN","prediction_labels":"HUMAN"},{"cleaned":"sleep problems increased risk mortality context advanced cancer background sleep problems linked increased mortality general population prevalence sleep problems diagnosed cancer even higher general population aims proposed study examine type prevalence sleep problems determine whether sleep problems associated survival advanced cancer patients methods study prospective design total 355 patients advanced cancers stage iii iv affecting hepatobiliary pancreatic systems administered battery questionnaires including pittsburgh sleep quality index psqi center epidemiological studies depression ces d scale descriptive statistics mann whitney u test cox regression analyses performed test aims results majority patients male 64 mean age 62 years sd 11 fifty nine percent patients reported poor sleep quality psqi 5 43 reported sleeping 6 hours 2 10 hours 27 reported sleep latency greater 30 minutes 3 nights per week 80 reported poor sleep efficiency less 85 time bed spent sleeping 19 reported taking sleep aid 3 times per week fifty eight percent patients reported clinically significant levels depression ces d 16 clinically significant depressive symptoms reported shorter sleep duration median 6 without clinical levels depression median 7 p 0 02 median survival entire sample 7 6 months adjusting factors known contribute survival e age gender vascular invasion depression snoring curvilinear relationship observed sleep duration mortality chi square 27 8 p 0 001 conclusions consistent findings general population curvilinear relationship sleep duration mortality observed advanced cancer patients google scholar","probabilities":0.9799733,"Title":"Sleep Problems And Increased Risk Of Mortality In The Context Of Advanced Cancer","Abstract":"Background: Sleep problems have been linked to increased mortality in the general population. The prevalence of sleep problems in those diagnosed with cancer is even higher than the general population. The aims of the proposed study were to examine the type and prevalence sleep problems, and to determine whether sleep problems are associated with survival, in advanced cancer patients. Methods: The study was prospective in design. A total of 355 patients with advanced cancers (stage III and IV) affecting the hepatobiliary and pancreatic systems were administered a battery of questionnaires including the Pittsburgh Sleep Quality Index (PSQI) and the Center for Epidemiological Studies-Depression (CES-D) scale. Descriptive statistics, Mann Whitney U test, and Cox regression analyses were performed to test the aims. Results: The majority of patients were male (64%) and the mean age 62 years (SD=11). Fifty-nine percent of patients reported poor sleep quality (PSQI > 5); 43% reported sleeping <6 hours and 2% > 10 hours; 27% reported sleep latency greater than 30 minutes for 3 or more nights per week; 80% reported poor sleep efficiency (less than 85% time in bed spent sleeping); and 19% reported taking a sleep aid 3 or more times per week. Fifty-eight percent of patients reported clinically significant levels of depression (CES-D >16) and those with clinically significant depressive symptoms reported shorter sleep duration (median=6) than those without clinical levels of depression (median=7; p=0.02). Median survival for the entire sample was 7.6 months. After adjusting for factors known to contribute to survival (i.e., age, gender, vascular invasion, depression, and snoring), a curvilinear relationship was observed between sleep duration and mortality (Chi-square=27.8, p=<0.001). Conclusions: Consistent with findings in the general population, a curvilinear relationship between sleep duration and mortality was observed in advanced cancer patients.","Source":"Google Scholar","category":"HUMAN","training_data":"Sleep Problems And Increased Risk Of Mortality In The Context Of Advanced Cancer Background: Sleep problems have been linked to increased mortality in the general population. The prevalence of sleep problems in those diagnosed with cancer is even higher than the general population. The aims of the proposed study were to examine the type and prevalence sleep problems, and to determine whether sleep problems are associated with survival, in advanced cancer patients. Methods: The study was prospective in design. A total of 355 patients with advanced cancers (stage III and IV) affecting the hepatobiliary and pancreatic systems were administered a battery of questionnaires including the Pittsburgh Sleep Quality Index (PSQI) and the Center for Epidemiological Studies-Depression (CES-D) scale. Descriptive statistics, Mann Whitney U test, and Cox regression analyses were performed to test the aims. Results: The majority of patients were male (64%) and the mean age 62 years (SD=11). Fifty-nine percent of patients reported poor sleep quality (PSQI > 5); 43% reported sleeping <6 hours and 2% > 10 hours; 27% reported sleep latency greater than 30 minutes for 3 or more nights per week; 80% reported poor sleep efficiency (less than 85% time in bed spent sleeping); and 19% reported taking a sleep aid 3 or more times per week. Fifty-eight percent of patients reported clinically significant levels of depression (CES-D >16) and those with clinically significant depressive symptoms reported shorter sleep duration (median=6) than those without clinical levels of depression (median=7; p=0.02). Median survival for the entire sample was 7.6 months. After adjusting for factors known to contribute to survival (i.e., age, gender, vascular invasion, depression, and snoring), a curvilinear relationship was observed between sleep duration and mortality (Chi-square=27.8, p=<0.001). Conclusions: Consistent with findings in the general population, a curvilinear relationship between sleep duration and mortality was observed in advanced cancer patients.\n Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"evaluation recommendation 8th edition american joint committee cancer ajcc staging system intrahepatic cholangiocarcinoma icc 820 patients surveillance epidemiology end results seer database background ajcc made four changes category 8th ajcc stage icc topic debate methods data 820 patients icc extracted seer database survival analysis 8th ajcc stage examined results verify four staging changes survival analysis prognosis patients tumor size 5 cm poorer tumor size 5 cm p 0 05 n0m0 cohort significant difference survival solitary tumor vascular invasion multiple tumors p 0 092 tumor perforating visceral peritoneum without involving local extrahepatic structures direct invasion p 0 470 tumor without periductal invasion pi p 0 220 prognosis patients 4 positive lymph nodes relatively poor compared 1 3 positive lymph nodes p 0 037 similar patients stage iv 8th ajcc p 0 585 conclusion study found significant difference survival tumor perforating visceral peritoneum without involving local extrahepatic structures direct invasion whereas staging changes effective inclusion number positive lymph nodes 8th ajcc stage may improve prognostic discrimination icc patients stn","probabilities":0.9799733,"Title":"Evaluation And Recommendation Of The 8Th Edition Of American Joint Committee On Cancer (Ajcc) Staging System For Intrahepatic Cholangiocarcinoma (Icc) In 820 Patients From The Surveillance Epidemiology And End Results (Seer) Database","Abstract":"Background: The AJCC made four changes to T category in the 8th AJCC stage for ICC, but this is a topic of debate. \r\n\r\n Methods: Data from 820 patients with ICC were extracted from the SEER database. Survival analysis of the 8th AJCC stage was examined. \r\n\r\n Results: To verify the four T staging changes by survival analysis: prognosis of patients with tumor size > 5 cm was poorer than that with tumor size ≤ 5 cm (P < 0.05); in N0M0 cohort, there was no significant difference in survival between solitary tumor with vascular invasion and multiple tumors (P = 0.092), tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion (P = 0.470), and tumor with and without periductal invasion (PI) (P = 0.220). The prognosis of patients with ≥ 4 positive lymph nodes was relatively poor compared with 1-3 positive lymph nodes (P = 0.037) and similar to patients with stage IV (8th AJCC, P = 0.585). \r\n\r\n Conclusion: This study found that there was no significant difference in survival between tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion, whereas other T staging changes were effective. The inclusion of the number of positive lymph nodes in the 8th AJCC stage may improve prognostic discrimination in ICC patients.","Source":"STN","category":"HUMAN","training_data":"Evaluation And Recommendation Of The 8Th Edition Of American Joint Committee On Cancer (Ajcc) Staging System For Intrahepatic Cholangiocarcinoma (Icc) In 820 Patients From The Surveillance Epidemiology And End Results (Seer) Database Background: The AJCC made four changes to T category in the 8th AJCC stage for ICC, but this is a topic of debate. \r\n\r\n Methods: Data from 820 patients with ICC were extracted from the SEER database. Survival analysis of the 8th AJCC stage was examined. \r\n\r\n Results: To verify the four T staging changes by survival analysis: prognosis of patients with tumor size > 5 cm was poorer than that with tumor size ≤ 5 cm (P < 0.05); in N0M0 cohort, there was no significant difference in survival between solitary tumor with vascular invasion and multiple tumors (P = 0.092), tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion (P = 0.470), and tumor with and without periductal invasion (PI) (P = 0.220). The prognosis of patients with ≥ 4 positive lymph nodes was relatively poor compared with 1-3 positive lymph nodes (P = 0.037) and similar to patients with stage IV (8th AJCC, P = 0.585). \r\n\r\n Conclusion: This study found that there was no significant difference in survival between tumor perforating the visceral peritoneum with and without involving local extrahepatic structures by direct invasion, whereas other T staging changes were effective. The inclusion of the number of positive lymph nodes in the 8th AJCC stage may improve prognostic discrimination in ICC patients. STN","prediction_labels":"HUMAN"},{"cleaned":"upregulated long noncoding rna pandar predicts unfavorable prognosis promotes tumorigenesis cholangiocarcinoma cholangiocarcinoma cca one malignant human cancers increasing incidence worldwide lncrnas emerged gene regulators prognostic biomarkers variety neoplasms pandar novel cancer related lncrna reported upregulated diverse human carcinomas study aimed investigate clinical significance lncrna pandar cca explore functional roles cca cells including cell proliferation apoptosis migration invasion epithelial mesenchymal transition emt results showed pandar significantly upregulated cca tissue specimens cell lines high expression closely associated lymph node invasion p 0 004 tnm stage p 0 034 postoperative relapse p 0 006 patients cca thus overexpression pandar serve independent prognostic biomarker cca furthermore silencing pandar followed sirna significantly inhibited cell proliferation increased apoptosis cca cells addition suppression pandar impaired migration invasion capacity vitro partly affecting emt overall findings showed lncrna pandar serves novel prognostic biomarker therapeutic target cca stn","probabilities":0.54545456,"Title":"Upregulated Long Noncoding Rna Pandar Predicts An Unfavorable Prognosis And Promotes Tumorigenesis In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is one of the most malignant human cancers with increasing incidence worldwide. LncRNAs have emerged as gene regulators and prognostic biomarkers in a variety of neoplasms. PANDAR, a novel cancer-related lncRNA, has been reported to be upregulated in diverse human carcinomas. In this study, we aimed to investigate the clinical significance of lncRNA PANDAR in CCA and explore its functional roles in CCA cells including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). The results showed that PANDAR was significantly upregulated in CCA tissue specimens and cell lines, and its high expression was closely associated with lymph node invasion (P=0.004), TNM stage (P=0.034) and postoperative relapse (P=0.006) in patients with CCA. Thus, overexpression of PANDAR could serve as an independent prognostic biomarker of CCA. Furthermore, silencing of PANDAR followed by siRNA significantly inhibited cell proliferation and increased apoptosis in CCA cells. In addition, suppression of PANDAR impaired migration and invasion capacity in vitro partly by affecting EMT. Overall, our findings showed that lncRNA PANDAR serves as a novel prognostic biomarker and therapeutic target for CCA.","Source":"STN","category":"ANIMAL","training_data":"Upregulated Long Noncoding Rna Pandar Predicts An Unfavorable Prognosis And Promotes Tumorigenesis In Cholangiocarcinoma Cholangiocarcinoma (CCA) is one of the most malignant human cancers with increasing incidence worldwide. LncRNAs have emerged as gene regulators and prognostic biomarkers in a variety of neoplasms. PANDAR, a novel cancer-related lncRNA, has been reported to be upregulated in diverse human carcinomas. In this study, we aimed to investigate the clinical significance of lncRNA PANDAR in CCA and explore its functional roles in CCA cells including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). The results showed that PANDAR was significantly upregulated in CCA tissue specimens and cell lines, and its high expression was closely associated with lymph node invasion (P=0.004), TNM stage (P=0.034) and postoperative relapse (P=0.006) in patients with CCA. Thus, overexpression of PANDAR could serve as an independent prognostic biomarker of CCA. Furthermore, silencing of PANDAR followed by siRNA significantly inhibited cell proliferation and increased apoptosis in CCA cells. In addition, suppression of PANDAR impaired migration and invasion capacity in vitro partly by affecting EMT. Overall, our findings showed that lncRNA PANDAR serves as a novel prognostic biomarker and therapeutic target for CCA. STN","prediction_labels":"HUMAN"},{"cleaned":"tumor lysate based vaccines road immunotherapy gallbladder cancer immunotherapy based checkpoint blockers proven survival benefits patients melanoma malignancies nevertheless significant proportion treated patients remains refractory suggesting combination active immunizations cancer vaccines helpful improve response rates last decade used dendritic cell dc based vaccines dcs loaded allogeneic heat conditioned melanoma cell lysate tested series clinical trials studies 60 stage iv melanoma dc treated patients showed immunological responses correlating improved survival studies showed essential part clinical efficacy associated use conditioned lysates gallbladder cancer gbc high incidence malignancy south america evaluated feasibility producing effective dcs using heat conditioned cell lysates derived gallbladder cancer cell lines gbccl characterizing nine different gbccls several fresh tumor tissues found expressed tumor associated antigens cea muc 1 ca19 9 erb2 survivin several carcinoembryonic antigens moreover heat shock treatment gbccls induced calreticulin translocation release hmgb1 atp known act danger signals monocytes stimulated combinations conditioned lysates exhibited potent increase dc maturation markers furthermore conditioned lysate matured dcs capable strongly inducing cd4 cd8 cell activation allogeneic autologous cell co cultures finally vitro stimulated cd8 cells recognize hla matched gbccls summary gbc cell lysate loaded dcs may considered future immunotherapy approaches pubmed","probabilities":0.875,"Title":"Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer","Abstract":"Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. In these studies, 60% of stage IV melanoma DC-treated patients showed immunological responses correlating with improved survival. Further studies showed that an essential part of the clinical efficacy was associated with the use of conditioned lysates. Gallbladder cancer (GBC) is a high-incidence malignancy in South America. Here, we evaluated the feasibility of producing effective DCs using heat-conditioned cell lysates derived from gallbladder cancer cell lines (GBCCL). By characterizing nine different GBCCLs and several fresh tumor tissues, we found that they expressed some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and several carcinoembryonic antigens. Moreover, heat-shock treatment of GBCCLs induced calreticulin translocation and release of HMGB1 and ATP, both known to act as danger signals. Monocytes stimulated with combinations of conditioned lysates exhibited a potent increase of DC-maturation markers. Furthermore, conditioned lysate-matured DCs were capable of strongly inducing CD4(+) and CD8(+) T cell activation, in both allogeneic and autologous cell co-cultures. Finally, in vitro stimulated CD8(+) T cells recognize HLA-matched GBCCLs. In summary, GBC cell lysate-loaded DCs may be considered for future immunotherapy approaches.","Source":"PubMed","category":"ANIMAL","training_data":"Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. In these studies, 60% of stage IV melanoma DC-treated patients showed immunological responses correlating with improved survival. Further studies showed that an essential part of the clinical efficacy was associated with the use of conditioned lysates. Gallbladder cancer (GBC) is a high-incidence malignancy in South America. Here, we evaluated the feasibility of producing effective DCs using heat-conditioned cell lysates derived from gallbladder cancer cell lines (GBCCL). By characterizing nine different GBCCLs and several fresh tumor tissues, we found that they expressed some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and several carcinoembryonic antigens. Moreover, heat-shock treatment of GBCCLs induced calreticulin translocation and release of HMGB1 and ATP, both known to act as danger signals. Monocytes stimulated with combinations of conditioned lysates exhibited a potent increase of DC-maturation markers. Furthermore, conditioned lysate-matured DCs were capable of strongly inducing CD4(+) and CD8(+) T cell activation, in both allogeneic and autologous cell co-cultures. Finally, in vitro stimulated CD8(+) T cells recognize HLA-matched GBCCLs. In summary, GBC cell lysate-loaded DCs may be considered for future immunotherapy approaches. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"upregulation oct4 acidic extracellular ph associated gemcitabine resistance cholangiocarcinoma cell lines background cholangiocarcinoma cca although uncommon liver cancer originating bile duct epithelial cells one top 10 fatal cancers chemoresistance unmet need always found cca patients tumor microenvironment conditions hypoxia nutrient starvation acidic extracellular ph play critical roles chemoresistance cancer progression however effect acidic extracellular ph cellular response chemoresistance cca studied methods human cca cell lines kku m213 kku m055 kku 100 cultured acidic ph 6 5 non acidic ph 7 4 condition used gene expression doubling time cytotoxicity assay results acidic extracellular ph ph 6 5 significantly increased doubling times cca cell lines compared non acidic condition ph 7 4 interestingly extracellular acid condition induced gemcitabine resistance cca cell lines showed octamer binding transcription factor 4 oct4 upregulated cell lines extracellular acid condition conclusion findings demonstrate cca cells adapt survive acidic environment chemoresistance developed oct4 may key transcriptional regulator mediates chemoresistance response acidic extracellular ph stn","probabilities":0.9467213,"Title":"The Upregulation Of Oct4 In Acidic Extracellular Ph Is Associated With Gemcitabine Resistance In Cholangiocarcinoma Cell Lines","Abstract":"Background: Cholangiocarcinoma (CCA), although is an uncommon liver cancer originating from bile duct epithelial cells, is one of the top 10 most fatal cancers. Chemoresistance is an unmet need always found in CCA patients. Tumor microenvironment conditions such as hypoxia, nutrient starvation and acidic extracellular pH play critical roles in chemoresistance and cancer progression. However, the effect of acidic extracellular pH on cellular response and chemoresistance in CCA has not been studied. Methods: Human CCA cell lines (KKU-M213, KKU-M055 and KKU-100) were cultured under acidic (pH 6.5) or non-acidic (pH 7.4) condition and were used for gene expression, doubling time and cytotoxicity assay. Results: The acidic extracellular pH (pH 6.5) significantly increased doubling times of CCA cell lines compared with non-acidic condition (pH 7.4). Interestingly, extracellular acid condition induced gemcitabine resistance in CCA cell lines. We showed that Octamer-binding transcription factor 4 (Oct4) was upregulated in these cell lines under extracellular acid condition. Conclusion: Our findings demonstrate that CCA cells can adapt to survive in acidic environment after which chemoresistance has been developed. Oct4 may be a key transcriptional regulator which mediates chemoresistance in response to acidic extracellular pH.","Source":"STN","category":"ANIMAL","training_data":"The Upregulation Of Oct4 In Acidic Extracellular Ph Is Associated With Gemcitabine Resistance In Cholangiocarcinoma Cell Lines Background: Cholangiocarcinoma (CCA), although is an uncommon liver cancer originating from bile duct epithelial cells, is one of the top 10 most fatal cancers. Chemoresistance is an unmet need always found in CCA patients. Tumor microenvironment conditions such as hypoxia, nutrient starvation and acidic extracellular pH play critical roles in chemoresistance and cancer progression. However, the effect of acidic extracellular pH on cellular response and chemoresistance in CCA has not been studied. Methods: Human CCA cell lines (KKU-M213, KKU-M055 and KKU-100) were cultured under acidic (pH 6.5) or non-acidic (pH 7.4) condition and were used for gene expression, doubling time and cytotoxicity assay. Results: The acidic extracellular pH (pH 6.5) significantly increased doubling times of CCA cell lines compared with non-acidic condition (pH 7.4). Interestingly, extracellular acid condition induced gemcitabine resistance in CCA cell lines. We showed that Octamer-binding transcription factor 4 (Oct4) was upregulated in these cell lines under extracellular acid condition. Conclusion: Our findings demonstrate that CCA cells can adapt to survive in acidic environment after which chemoresistance has been developed. Oct4 may be a key transcriptional regulator which mediates chemoresistance in response to acidic extracellular pH. STN","prediction_labels":"ANIMAL"},{"cleaned":"feasibility gemcitabine oxaliplatin patients advanced biliary tract carcinoma performance status 2 use gemcitabine oxaliplatin well documented selected patients advanced biliary tract carcinoma btc little known feasibility systemic treatments patients performance status ps 2 retrospectively examined medical records consecutive btc patients ps 2 receiving gemcitabine 1000 mg m 2 plus oxaliplatin 100 mg m 2 every 2 weeks january 2003 december 2011 institution body composition analysed computed tomography scan detect sarcopenia primary evaluation criterion safety secondary evaluation criteria response rate progression free survival pfs overall survival os twenty eight patients median age 63 years range 41 83 received total 175 cycles median per patient 6 range 2 12 ten patients 35 7 sarcopenia pretreatment computed tomography scan frequent toxicities thrombocytopenia grades 2 4 n 4 14 3 peripheral neuropathy grades 2 3 n 9 32 1 cholangitis n 4 14 3 best response partial response 10 7 patients 95 confidence interval ci 0 22 2 stable disease 42 9 patients median pfs os 4 6 95 ci 2 5 6 3 7 5 95 ci 5 2 9 5 months respectively median pfs os significantly longer patients without sarcopenia 7 0 months 95 ci 4 4 8 0 vs 2 2 months 95 ci 2 0 2 5 p less 0 01 10 4 months 95 ci 7 5 11 6 vs 4 9 months 95 ci 3 7 5 2 p less 0 01 respectively experience gemcitabine oxaliplatin feasible induced effective palliation ps2 patients advanced btc studies warranted confirm findings pubmed","probabilities":0.9799733,"Title":"Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2","Abstract":"The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41-83) received a total of 175 cycles (median per patient: 6, range 2-12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2-4: n=4, 14.3%), peripheral neuropathy (grades 2-3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0-22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5-6.3) and 7.5 (95% CI: 5.2-9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4-8.0) vs. 2.2 months (95% CI: 2.0-2.5), P less than 0.01, and 10.4 months (95% CI: 7.5-11.6) vs. 4.9 months (95% CI: 3.7-5.2), P less than 0.01, respectively. In our experience, gemcitabine-oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings.","Source":"PubMed","category":"HUMAN","training_data":"Feasibility of gemcitabine and oxaliplatin in patients with advanced biliary tract carcinoma and a performance status of 2 The use of gemcitabine and oxaliplatin is well documented in selected patients with advanced biliary tract carcinoma (BTC), but little is known on the feasibility of systemic treatments in patients with a performance status (PS) of 2. We retrospectively examined the medical records of consecutive BTC patients with a PS of 2 receiving gemcitabine 1000 mg/m(2) plus oxaliplatin 100 mg/m(2) every 2 weeks from January 2003 to December 2011 in our institution. Body composition was analysed by computed tomography scan to detect sarcopenia. The primary evaluation criterion was safety. The secondary evaluation criteria were the response rate, progression-free survival (PFS) and overall survival (OS). Twenty-eight patients (median age: 63 years, range 41-83) received a total of 175 cycles (median per patient: 6, range 2-12). Ten patients (35.7%) had sarcopenia on the pretreatment computed tomography scan. The most frequent toxicities were thrombocytopenia (grades 2-4: n=4, 14.3%), peripheral neuropathy (grades 2-3: n=9, 32.1%) and cholangitis (n=4, 14.3%). The best response was a partial response in 10.7% of patients [95% confidence interval (CI): 0-22.2] and stable disease in 42.9% of patients. The median PFS and OS were 4.6 (95% CI: 2.5-6.3) and 7.5 (95% CI: 5.2-9.5) months, respectively. The median PFS and OS were significantly longer in patients without sarcopenia: 7.0 months (95% CI: 4.4-8.0) vs. 2.2 months (95% CI: 2.0-2.5), P less than 0.01, and 10.4 months (95% CI: 7.5-11.6) vs. 4.9 months (95% CI: 3.7-5.2), P less than 0.01, respectively. In our experience, gemcitabine-oxaliplatin was feasible and induced effective palliation in PS2 patients with advanced BTC. Further studies are warranted to confirm these findings. PubMed","prediction_labels":"HUMAN"},{"cleaned":"trends gallbladder cancer incidence rates poland relation changes diet tobacco smoking period 1970 2008 background gallbladder cancer affects predominantly female population standardised incidence rate poland 2008 amounted 2 2 100 thousand females 0 7 100 thousand males rates rather stable 1970 half 90 20th century downward trends observed aim study identify dietary factors contribute trends taking tobacco smoking account also methods standardised gallbladder cancer incidence rates according gender covering individual years since 1970 2008 derived national cancer registry administered institute oncology information source dietary trends time period database established national food nutrition institute database covers data derived national food balance sheets showing food quantities available consumption per capita year original calculations amounts energy nutrients food information tobacco smoking showing number cigarettes per capita year derived national statistical yearbooks spearman rank correlation coef cient rs used measure relationship examined variables dietary variables included total energy vitamin c intake consumption alcohol tea coffee results positive correlations found gallbladder cancer incidence rates energy intake rs 0 50 females 0 83 males energy intake signi cantly decreased period 1970 2008 3427 3038 kcal person day adverse correlations rs 0 51 women 0 67 men noted respect vitamin c intake increased especially 90 20th century present much higher 70 80 adverse correlations observed also tea rs 0 45 females 0 40 males coffee consumption rs 0 58 0 60 respectively gallbladder cancer morbidity positively correlated tobacco smoking rs 0 49 women 0 69 men obtained results indicate correlations gallbladder cancer incidence rates alcohol consumption taking account individual years analysis however early 80 important decline alcohol consumption noted development contribute decrease gallbladder cancer morbidity observed later conclusions seems trends gallbladder cancer incidence rates 19702008in poland affected bylowering energy intake andhigher vitamin c content average diet increase tea coffee consumption play positive role also downward trends observed gallbladder cancer morbidity since half 90 affected factors decrease tobacco smoking also earlier decline alcohol consumption possible factor uencing trends statistical analysis con rm google scholar","probabilities":0.9799733,"Title":"Trends In Gallbladder Cancer Incidence Rates In Poland In Relation To Changes In The Diet And Tobacco Smoking During The Period Of 1970-2008","Abstract":"Background: Gallbladder cancer affects predominantly female population. Its standardised incidence rate in Poland in 2008 amounted to 2.2/100 thousand for females and 0.7/100 thousand for males. These rates were rather stable between 1970 and the half of the 90’s of 20th century and then the downward trends were observed. The aim of the study was to identify the dietary factors, which could contribute to these trends taking tobacco smoking into account also. Methods: Standardised gallbladder cancer incidence rates according to gender and covering individual years since 1970 to 2008 were derived from the National Cancer Registry administered by the Institute of Oncology. The information source on the dietary trends in the same time period was database established by the National Food and Nutrition Institute. This database covers data derived from the national food balance sheets showing food quantities available for consumption per capita/year and original calculations on the amounts of the energy and nutrients from food. Information on tobacco smoking showing number of cigarettes per capita/year was derived from national statistical yearbooks. The Spearman rank correlation coefficient (rs) was used as a measure of the relationship between examined variables. Dietary variables included total energy and vitamin C intake and the consumption of alcohol, tea and coffee. Results: Positive correlations were found for gallbladder cancer incidence rates and energy intake, with rs=0.50 for females and 0.83 for males. Energy intake significantly decreased during the period 1970-2008 – from 3427 to 3038 kcal/person/day. Adverse correlations (rs=-0.51 for women and -0.67 for men) were noted with respect to vitamin C intake, which increased especially during the 90’s of 20th century and at present is much higher than in the 70’s and 80’s. Adverse correlations were observed also for tea (rs=-0.45 for females and -0.40 for males) and coffee consumption (rs=-0.58 and -0.60 respectively). Gallbladder cancer morbidity positively correlated with tobacco smoking (rs=0.49 for women and 0.69 for men). Obtained results do not indicate correlations between gallbladder cancer incidence rates and alcohol consumption taking into account all individual years of the analysis. However in the in the early 80’s an important decline in alcohol consumption was noted and this development could contribute to decrease in gallbladder cancer morbidity observed later. Conclusions: It seems that the trends in gallbladder cancer incidence rates in 19702008in Poland were affected bylowering energy intake andhigher vitamin C content in average diet. The increase in tea and coffee consumption could play a positive role also. The downward trends observed in gallbladder cancer morbidity since the half of the 90’s could be affected by other factors such as the decrease in tobacco smoking. Also the earlier decline in alcohol consumption could be possible factor influencing these trends, but statistical analysis did not confirm it.","Source":"Google Scholar","category":"HUMAN","training_data":"Trends In Gallbladder Cancer Incidence Rates In Poland In Relation To Changes In The Diet And Tobacco Smoking During The Period Of 1970-2008 Background: Gallbladder cancer affects predominantly female population. Its standardised incidence rate in Poland in 2008 amounted to 2.2/100 thousand for females and 0.7/100 thousand for males. These rates were rather stable between 1970 and the half of the 90’s of 20th century and then the downward trends were observed. The aim of the study was to identify the dietary factors, which could contribute to these trends taking tobacco smoking into account also. Methods: Standardised gallbladder cancer incidence rates according to gender and covering individual years since 1970 to 2008 were derived from the National Cancer Registry administered by the Institute of Oncology. The information source on the dietary trends in the same time period was database established by the National Food and Nutrition Institute. This database covers data derived from the national food balance sheets showing food quantities available for consumption per capita/year and original calculations on the amounts of the energy and nutrients from food. Information on tobacco smoking showing number of cigarettes per capita/year was derived from national statistical yearbooks. The Spearman rank correlation coefficient (rs) was used as a measure of the relationship between examined variables. Dietary variables included total energy and vitamin C intake and the consumption of alcohol, tea and coffee. Results: Positive correlations were found for gallbladder cancer incidence rates and energy intake, with rs=0.50 for females and 0.83 for males. Energy intake significantly decreased during the period 1970-2008 – from 3427 to 3038 kcal/person/day. Adverse correlations (rs=-0.51 for women and -0.67 for men) were noted with respect to vitamin C intake, which increased especially during the 90’s of 20th century and at present is much higher than in the 70’s and 80’s. Adverse correlations were observed also for tea (rs=-0.45 for females and -0.40 for males) and coffee consumption (rs=-0.58 and -0.60 respectively). Gallbladder cancer morbidity positively correlated with tobacco smoking (rs=0.49 for women and 0.69 for men). Obtained results do not indicate correlations between gallbladder cancer incidence rates and alcohol consumption taking into account all individual years of the analysis. However in the in the early 80’s an important decline in alcohol consumption was noted and this development could contribute to decrease in gallbladder cancer morbidity observed later. Conclusions: It seems that the trends in gallbladder cancer incidence rates in 19702008in Poland were affected bylowering energy intake andhigher vitamin C content in average diet. The increase in tea and coffee consumption could play a positive role also. The downward trends observed in gallbladder cancer morbidity since the half of the 90’s could be affected by other factors such as the decrease in tobacco smoking. Also the earlier decline in alcohol consumption could be possible factor influencing these trends, but statistical analysis did not confirm it. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"free episomal integrated hbv dna hbsag negative patients intrahepatic cholangiocarcinoma evidence chronic hepatitis b virus hbv infection associated increased risk intrahepatic cholangiocarcinoma icc development hypothesized etiological role hbv development tumor little known occult hbv infection obi icc aims study investigate obi prevalence characterize hbv molecular status intrahepatic level obi positive cases icc frozen liver tumor specimens 47 hbv surface antigen negative patients icc 41 paired non tumor liver tissues tested obi 4 different hbv specific nested pcr covalently closed circular hbv dna hbv cccdna viral integrations investigated obi positive cases hbv dna detected tumor non tumor specimens 29 47 61 7 icc patients hbv cccdna found tissues 5 17 34 5 cases examined hbv integration detected 4 10 40 tumor tissues tested involved hbx hbv core gene sequences 3 1 cases respectively viral integration occurred 9 367 nucleotides upstream cat eye syndrome critical region protein 5 isoform coding sequence b within cystinosin isoform 1 precursor gene c within thromboxane synthase 1 gene d within atpase phospholipid transporting 9b gene occult hbv infection highly prevalent patients icc free viral genomes integrated hbv dna present cases results suggest involvement hbv carcinogenic process leading icc development even cases occult infection stn","probabilities":0.9285714,"Title":"Free Episomal And Integrated Hbv Dna In Hbsag-Negative Patients With Intrahepatic Cholangiocarcinoma","Abstract":"There is evidence that chronic hepatitis B virus (HBV) infection is associated with an increased risk of intrahepatic cholangiocarcinoma (ICC) development, and it has been hypothesized an etiological role of HBV in the development of this tumor. Very little is known about occult HBV infection (OBI) in ICC. Aims of the study were to investigate the OBI prevalence and to characterize the HBV molecular status at intrahepatic level in OBI-positive cases with ICC. Frozen liver tumor specimens from 47 HBV surface-antigen-negative patients with ICC and 41 paired non-tumor liver tissues were tested for OBI by 4 different HBV-specific nested PCR. Covalently closed circular HBV DNA (HBV cccDNA) and viral integrations were investigated in OBI-positive cases. HBV DNA was detected in tumor and/or non-tumor specimens from 29/47 (61.7%) ICC patients. HBV cccDNA was found in tissues from 5/17 (34.5%) cases examined. HBV integration was detected in 4/10 (40%) tumor tissues tested and involved HBx and HBV-core gene sequences in 3 and 1 cases, respectively. Viral integration occurred: (a) 9,367 nucleotides upstream of the cat-eye-syndrome critical region protein-5-isoform coding sequence; (b) within the cystinosin isoform-1-precursor gene; (c) within the thromboxane-A-synthase-1 gene; (d) within the ATPase phospholipid transporting 9B gene. Occult HBV infection is highly prevalent in patients with ICC. Both free viral genomes and integrated HBV DNA can be present in these cases. These results suggest an involvement of HBV in the carcinogenic process leading to ICC development even in cases with occult infection.","Source":"STN","category":"ANIMAL","training_data":"Free Episomal And Integrated Hbv Dna In Hbsag-Negative Patients With Intrahepatic Cholangiocarcinoma There is evidence that chronic hepatitis B virus (HBV) infection is associated with an increased risk of intrahepatic cholangiocarcinoma (ICC) development, and it has been hypothesized an etiological role of HBV in the development of this tumor. Very little is known about occult HBV infection (OBI) in ICC. Aims of the study were to investigate the OBI prevalence and to characterize the HBV molecular status at intrahepatic level in OBI-positive cases with ICC. Frozen liver tumor specimens from 47 HBV surface-antigen-negative patients with ICC and 41 paired non-tumor liver tissues were tested for OBI by 4 different HBV-specific nested PCR. Covalently closed circular HBV DNA (HBV cccDNA) and viral integrations were investigated in OBI-positive cases. HBV DNA was detected in tumor and/or non-tumor specimens from 29/47 (61.7%) ICC patients. HBV cccDNA was found in tissues from 5/17 (34.5%) cases examined. HBV integration was detected in 4/10 (40%) tumor tissues tested and involved HBx and HBV-core gene sequences in 3 and 1 cases, respectively. Viral integration occurred: (a) 9,367 nucleotides upstream of the cat-eye-syndrome critical region protein-5-isoform coding sequence; (b) within the cystinosin isoform-1-precursor gene; (c) within the thromboxane-A-synthase-1 gene; (d) within the ATPase phospholipid transporting 9B gene. Occult HBV infection is highly prevalent in patients with ICC. Both free viral genomes and integrated HBV DNA can be present in these cases. These results suggest an involvement of HBV in the carcinogenic process leading to ICC development even in cases with occult infection. STN","prediction_labels":"ANIMAL"},{"cleaned":"evaluation treatment outcome incidental gallbladder cancer hospital abstract available google scholar","probabilities":0.9799733,"Title":"Evaluation Of The Treatment Outcome Of Incidental Gallbladder Cancer In Our Hospital","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Evaluation Of The Treatment Outcome Of Incidental Gallbladder Cancer In Our Hospital Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"acgh detects distinct genomic alterations primary intrahepatic cholangiocarcinomas matched lymph node metastases identifies poor prognosis subclass lymph node metastases lnm important prognostic factor patients intrahepatic cholangiocarcinoma underlying genetic alterations poorly understood whole genome array comparative genomic hybridization acgh performed 37 tumors 14 matched lnm genomic analyses tumors confirmed known identified new gains 19q copy number alterations cna tumors lnm n1 alterations exclusive gains 3p 4q 5p 13q losses 17p 20p lnm shared alterations matched tumors 86 79 acquired new isolated gains 12q14 36 1p13 2p23 7p22 7q11 11q12 13q13 14q12 20 unsupervised clustering revealed poor prognosis subclass increased alterations significantly associated tumor differentiation survival tp53 kras mutations occurred 19 tumors 6 metastases pathway analyses revealed association cancer associated pathways advanced tumor stage microvascular perineural invasion microscopic positive resection margin r1 significantly correlated metastases n1 status r1 resection poor tumor differentiation significantly correlated survival acgh identified clear differences n0 lnm n1 tumors n1 tumors matched lnm displayed high clonality exclusive gains metastases novel subclass increased cnas poor tumor differentiation significantly correlated survival pubmed","probabilities":0.9799733,"Title":"ACGH detects distinct genomic alterations of primary intrahepatic cholangiocarcinomas and matched lymph node metastases and identifies a poor prognosis subclass","Abstract":"Lymph node metastases (LNM) are an important prognostic factor for patients with intrahepatic cholangiocarcinoma, but underlying genetic alterations are poorly understood. Whole genome array comparative genomic hybridization (aCGH) was performed in 37 tumors and 14 matched LNM. Genomic analyses of tumors confirmed known and identified new (gains in 19q) copy number alterations (CNA). Tumors with LNM (N1) had more alterations and exclusive gains (3p, 4q, 5p, 13q) and losses (17p and 20p). LNM shared most alterations with their matched tumors (86%), but 79% acquired new isolated gains [12q14 (36%); 1p13, 2p23, 7p22, 7q11, 11q12, 13q13 and 14q12 (>20%)]. Unsupervised clustering revealed a poor prognosis subclass with increased alterations significantly associated to tumor differentiation and survival. TP53 and KRAS mutations occurred in 19% of tumors and 6% of metastases. Pathway analyses revealed association to cancer-associated pathways. Advanced tumor stage, microvascular/perineural invasion, and microscopic positive resection margin (R1) were significantly correlated to metastases, while N1-status, R1-resection, and poor tumor differentiation were significantly correlated to survival. ACGH identified clear differences between N0 (no LNM) and N1 tumors, while N1 tumors and matched LNM displayed high clonality with exclusive gains in the metastases. A novel subclass with increased CNAs and poor tumor differentiation was significantly correlated to survival.","Source":"PubMed","category":"HUMAN","training_data":"ACGH detects distinct genomic alterations of primary intrahepatic cholangiocarcinomas and matched lymph node metastases and identifies a poor prognosis subclass Lymph node metastases (LNM) are an important prognostic factor for patients with intrahepatic cholangiocarcinoma, but underlying genetic alterations are poorly understood. Whole genome array comparative genomic hybridization (aCGH) was performed in 37 tumors and 14 matched LNM. Genomic analyses of tumors confirmed known and identified new (gains in 19q) copy number alterations (CNA). Tumors with LNM (N1) had more alterations and exclusive gains (3p, 4q, 5p, 13q) and losses (17p and 20p). LNM shared most alterations with their matched tumors (86%), but 79% acquired new isolated gains [12q14 (36%); 1p13, 2p23, 7p22, 7q11, 11q12, 13q13 and 14q12 (>20%)]. Unsupervised clustering revealed a poor prognosis subclass with increased alterations significantly associated to tumor differentiation and survival. TP53 and KRAS mutations occurred in 19% of tumors and 6% of metastases. Pathway analyses revealed association to cancer-associated pathways. Advanced tumor stage, microvascular/perineural invasion, and microscopic positive resection margin (R1) were significantly correlated to metastases, while N1-status, R1-resection, and poor tumor differentiation were significantly correlated to survival. ACGH identified clear differences between N0 (no LNM) and N1 tumors, while N1 tumors and matched LNM displayed high clonality with exclusive gains in the metastases. A novel subclass with increased CNAs and poor tumor differentiation was significantly correlated to survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radiomics radiogenomics primary liver cancers concurrent advancements imaging genomic biomarkers created opportunities identify non invasive imaging surrogates molecular phenotypes order develop imaging surrogates radiomics radiogenomics imaging genomics necessary consistent progress fields primary liver cancers article evaluate current status field specifically regards hepatocellular carcinoma intrahepatic cholangiocarcinoma highlighting coming results presented annual radiological society north america conference 2017 increasing number studies area bias towards quantitative feature measurement expected benefit reproducibility findings portends well future development biomarkers diagnosis prognosis treatment response assessment review advancements look forward exciting future applications anticipated field develops pubmed","probabilities":0.9799733,"Title":"Radiomics and radiogenomics of primary liver cancers","Abstract":"Concurrent advancements in imaging and genomic biomarkers have created opportunities to identify non-invasive imaging surrogates of molecular phenotypes. In order to develop such imaging surrogates radiomics and radiogenomics/imaging genomics will be necessary; there has been consistent progress in these fields for primary liver cancers. In this article we evaluate the current status of the field specifically with regards to hepatocellular carcinoma and intrahepatic cholangiocarcinoma, highlighting some of the up and coming results that were presented at the annual Radiological Society of North America Conference in 2017. There are an increasing number of studies in this area with a bias towards quantitative feature measurement, which is expected to benefit reproducibility of the findings and portends well for the future development of biomarkers for diagnosis, prognosis, and treatment response assessment. We review some of the advancements and look forward to some of the exciting future applications that are anticipated as the field develops.","Source":"PubMed","category":"HUMAN","training_data":"Radiomics and radiogenomics of primary liver cancers Concurrent advancements in imaging and genomic biomarkers have created opportunities to identify non-invasive imaging surrogates of molecular phenotypes. In order to develop such imaging surrogates radiomics and radiogenomics/imaging genomics will be necessary; there has been consistent progress in these fields for primary liver cancers. In this article we evaluate the current status of the field specifically with regards to hepatocellular carcinoma and intrahepatic cholangiocarcinoma, highlighting some of the up and coming results that were presented at the annual Radiological Society of North America Conference in 2017. There are an increasing number of studies in this area with a bias towards quantitative feature measurement, which is expected to benefit reproducibility of the findings and portends well for the future development of biomarkers for diagnosis, prognosis, and treatment response assessment. We review some of the advancements and look forward to some of the exciting future applications that are anticipated as the field develops. PubMed","prediction_labels":"HUMAN"},{"cleaned":"dmbt1 expression biliary carcinogenesis correlation clinicopathological data aims deleted malignant brain tumours 1 dmbt1 exerts functions regulation epithelial differentiation inflammation proposed tumour suppressor chronic inflammation hallmark cholangiocarcinogenesis aim study investigate expression dmbt1 biliary tract cancer btc correlate expression clinicopathological data methods results expression dmbt1 protein examined immunohistochemically 157 btc patients 41 intrahepatic icc 60 extrahepatic cholangiocarcinomas ecc 56 adenocarcinomas gallbladder gbac additionally 56 samples high grade biliary intraepithelial neoplasia bilin 3 92 corresponding samples histological non neoplastic biliary tract tissues included dmbt1 expression increased significantly bilin 3 compared normal tissue p 0 0001 btc p 0 0001 btc showed significant difference dmbt1 expression compared non neoplastic biliary tissue p 0 315 absent dmbt1 expression non neoplastic biliary tissue btc patients associated poorer survival p 0 027 dmbt1 expression correlated significantly patients age p 0 001 conclusion dmbt1 expressed differently cholangiocarcinogenesis poorer patients survival rates associated absent dmbt1 expression non neoplastic biliary tissue suggesting tumour suppressive role dmbt1 early cholangiocarcinogenesis pubmed","probabilities":0.7777778,"Title":"DMBT1 expression in biliary carcinogenesis with correlation of clinicopathological data","Abstract":"AIMS: Deleted in malignant brain tumours 1 (DMBT1) exerts functions in the regulation of epithelial differentiation and inflammation and has been proposed as a tumour suppressor. Because chronic inflammation is a hallmark of cholangiocarcinogenesis, the aim of this study was to investigate the expression of DMBT1 in biliary tract cancer (BTC) and to correlate this expression with clinicopathological data. METHODS AND RESULTS: The expression of DMBT1 protein was examined immunohistochemically in 157 BTC patients [41 intrahepatic (ICC), 60 extrahepatic cholangiocarcinomas (ECC) and 56 adenocarcinomas of the gallbladder (GBAC)]. Additionally, 56 samples of high-grade biliary intraepithelial neoplasia (BilIN 3) and 92 corresponding samples of histological non-neoplastic biliary tract tissues were included. DMBT1 expression was increased significantly in BilIN 3 compared to normal tissue (P < 0.0001) and BTC (P < 0.0001). BTC showed no significant difference in DMBT1 expression compared to non-neoplastic biliary tissue (P = 0.315). Absent DMBT1 expression in non-neoplastic biliary tissue of BTC patients was associated with poorer survival (P = 0.027). DMBT1 expression was correlated significantly with patients' age (P < 0.001). CONCLUSION: DMBT1 is expressed differently in cholangiocarcinogenesis and poorer patients' survival rates are associated with absent DMBT1 expression in non-neoplastic biliary tissue, suggesting a tumour-suppressive role of DMBT1 in early cholangiocarcinogenesis.","Source":"PubMed","category":"ANIMAL","training_data":"DMBT1 expression in biliary carcinogenesis with correlation of clinicopathological data AIMS: Deleted in malignant brain tumours 1 (DMBT1) exerts functions in the regulation of epithelial differentiation and inflammation and has been proposed as a tumour suppressor. Because chronic inflammation is a hallmark of cholangiocarcinogenesis, the aim of this study was to investigate the expression of DMBT1 in biliary tract cancer (BTC) and to correlate this expression with clinicopathological data. METHODS AND RESULTS: The expression of DMBT1 protein was examined immunohistochemically in 157 BTC patients [41 intrahepatic (ICC), 60 extrahepatic cholangiocarcinomas (ECC) and 56 adenocarcinomas of the gallbladder (GBAC)]. Additionally, 56 samples of high-grade biliary intraepithelial neoplasia (BilIN 3) and 92 corresponding samples of histological non-neoplastic biliary tract tissues were included. DMBT1 expression was increased significantly in BilIN 3 compared to normal tissue (P < 0.0001) and BTC (P < 0.0001). BTC showed no significant difference in DMBT1 expression compared to non-neoplastic biliary tissue (P = 0.315). Absent DMBT1 expression in non-neoplastic biliary tissue of BTC patients was associated with poorer survival (P = 0.027). DMBT1 expression was correlated significantly with patients' age (P < 0.001). CONCLUSION: DMBT1 is expressed differently in cholangiocarcinogenesis and poorer patients' survival rates are associated with absent DMBT1 expression in non-neoplastic biliary tissue, suggesting a tumour-suppressive role of DMBT1 in early cholangiocarcinogenesis. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"regulation cell proliferation migration gallbladder cancer zinc finger x chromosomal protein gallbladder carcinoma gbc one mostly aggressive fatal malignancies however little known oncogenic genes contributed development gbc zinc finger x chromosomal protein zfx novel member krueppel c2h2 type zinc finger protein family regulation led impaired cell growth human laryngeal squamous cell carcinoma aim investigate function zfx gbc cell proliferation migration loss function analysis performed gbc cell line gbc sd using lentivirus mediated sirna zfx proliferation vitro tumorigenesis colony formation ability well cell migration significantly suppressed gbc sd cells infected zfx sirna expressing lentivirus lv shzfx finding suggested zfx promoted growth migration gbc cells present potential molecular target gene therapy gbc google scholar","probabilities":0.9467213,"Title":"Regulation Of Cell Proliferation And Migration In Gallbladder Cancer By Zinc Finger X-Chromosomal Protein","Abstract":"Gallbladder carcinoma (GBC) is one of the mostly aggressive and fatal malignancies. However, little is known about the oncogenic genes that contributed to the development of GBC. Zinc finger X-chromosomal protein (ZFX) was a novel member of the Krueppel C2H2-type zinc-finger protein family and its down-regulation led to impaired cell growth in human laryngeal squamous cell carcinoma. Here, we aim to investigate the function of ZFX in GBC cell proliferation and migration. Loss of function analysis was performed on GBC cell line (GBC-SD) using lentivirus-mediated siRNA against ZFX. The proliferation, in vitro tumorigenesis (colony-formation) ability as well as cell migration was significantly suppressed after GBC-SD cells which were infected with ZFX-siRNA-expressing lentivirus (Lv-shZFX). Our finding suggested that ZFX promoted the growth and migration of GBC cells and could present a potential molecular target for gene therapy of GBC.","Source":"Google Scholar","category":"ANIMAL","training_data":"Regulation Of Cell Proliferation And Migration In Gallbladder Cancer By Zinc Finger X-Chromosomal Protein Gallbladder carcinoma (GBC) is one of the mostly aggressive and fatal malignancies. However, little is known about the oncogenic genes that contributed to the development of GBC. Zinc finger X-chromosomal protein (ZFX) was a novel member of the Krueppel C2H2-type zinc-finger protein family and its down-regulation led to impaired cell growth in human laryngeal squamous cell carcinoma. Here, we aim to investigate the function of ZFX in GBC cell proliferation and migration. Loss of function analysis was performed on GBC cell line (GBC-SD) using lentivirus-mediated siRNA against ZFX. The proliferation, in vitro tumorigenesis (colony-formation) ability as well as cell migration was significantly suppressed after GBC-SD cells which were infected with ZFX-siRNA-expressing lentivirus (Lv-shZFX). Our finding suggested that ZFX promoted the growth and migration of GBC cells and could present a potential molecular target for gene therapy of GBC. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"hepatitis b virus associated clinical features survival rate patients intrahepatic cholangiocarcinoma background objective pathogenesis development intrahepatic cholangiocarcinoma icc may triggered hepatitis b virus hbv conducted retrospective study explore potential association hbv infection clinical features survival rate patients icc methods patients icc undergone curative resection enrolled divided three groups according seropositivity hepatitis b surface antigen hbsag hepatitis b core antibody anti hbc groups follows group hbsag anti hbc group ii hbsag anti hbc group iii hbsag anti hbc symptoms pathologic findings outcome information patients retrospectively reviewed patient sera isolated detect anti hcv hbsag anti hbc surgical specimens assessed hematoxylin eosin staining expression cytokeratin 7 evaluated immunohistochemistry finally 1 3 5 year cumulative survival rates analyzed results ninety seven patients icc enrolled group n 26 group ii n 50 group iii n 21 total 26 8 26 97 patients icc positive hbsag patients hbv associated icc tended younger p 0 018 lower ca19 9 levels p 0 000 higher alpha fetal protein afp level p 0 012 prothrombin time p 0 030 higher risk hepatic cirrhosis p 0 001 poor differentiation p 0 028 1 3 5 year cumulative survival rates patients within three groups follows 27 3 0 0 group respectively 62 5 30 0 0 group ii respectively 87 5 66 7 50 0 group iii respectively results significantly different overall comparison p 0 000 conclusion patients hbv associated icc showed different clinicopathological features lower survival rates compared patients icc without hbv infection pubmed","probabilities":0.9799733,"Title":"Hepatitis B virus is associated with the clinical features and survival rate of patients with intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND AND OBJECTIVE: The pathogenesis and development of intrahepatic cholangiocarcinoma (ICC) may be triggered by hepatitis B virus (HBV). We conducted this retrospective study to explore the potential association between HBV infection and the clinical features and survival rate of patients with ICC. METHODS: Patients with ICC who had undergone a curative resection were enrolled and divided into three groups according to the seropositivity of the hepatitis B surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). The groups were as follows: group I, HBsAg (+)/anti-HBc (+); group II, HBsAg (-)/anti-HBc (+); group III HBsAg (-)/anti-HBc (-). The symptoms, pathologic findings, and outcome information of all patients were retrospectively reviewed. The patient sera were isolated to detect anti-HCV, HBsAg, and anti-HBc. Surgical specimens were assessed by hematoxylin and eosin (HE) staining. The expression of cytokeratin 7 was evaluated by immunohistochemistry. Finally, the 1-, 3-, and 5-year cumulative survival rates were analyzed. RESULTS: Ninety-seven patients with ICC were enrolled in group I (n=26); group II, (n=50), and group III (n=21). A total of 26.8% (26/97) patients with ICC were positive for HBsAg. Patients with HBV-associated ICC tended to be younger (P=0.018), have lower CA19-9 levels (P=0.000), a higher alpha fetal protein (AFP) level (P=0.012) and prothrombin time (P=0.030), a higher risk of hepatic cirrhosis (P=0.001), and poor differentiation (P=0.028). The 1-, 3-, and 5-year cumulative survival rates for patients within the three groups were as follows: 27.3%, 0%, and 0% for group I, respectively; 62.5%, 30.0%, and 0% for group II, respectively; and 87.5%, 66.7%, and 50.0% for group III, respectively. The results were significantly different in an overall comparison (P=0.000). CONCLUSION: Patients with HBV-associated ICC showed different clinicopathological features and lower survival rates compared to patients with ICC without HBV infection.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis B virus is associated with the clinical features and survival rate of patients with intrahepatic cholangiocarcinoma BACKGROUND AND OBJECTIVE: The pathogenesis and development of intrahepatic cholangiocarcinoma (ICC) may be triggered by hepatitis B virus (HBV). We conducted this retrospective study to explore the potential association between HBV infection and the clinical features and survival rate of patients with ICC. METHODS: Patients with ICC who had undergone a curative resection were enrolled and divided into three groups according to the seropositivity of the hepatitis B surface antigen (HBsAg) and the hepatitis B core antibody (anti-HBc). The groups were as follows: group I, HBsAg (+)/anti-HBc (+); group II, HBsAg (-)/anti-HBc (+); group III HBsAg (-)/anti-HBc (-). The symptoms, pathologic findings, and outcome information of all patients were retrospectively reviewed. The patient sera were isolated to detect anti-HCV, HBsAg, and anti-HBc. Surgical specimens were assessed by hematoxylin and eosin (HE) staining. The expression of cytokeratin 7 was evaluated by immunohistochemistry. Finally, the 1-, 3-, and 5-year cumulative survival rates were analyzed. RESULTS: Ninety-seven patients with ICC were enrolled in group I (n=26); group II, (n=50), and group III (n=21). A total of 26.8% (26/97) patients with ICC were positive for HBsAg. Patients with HBV-associated ICC tended to be younger (P=0.018), have lower CA19-9 levels (P=0.000), a higher alpha fetal protein (AFP) level (P=0.012) and prothrombin time (P=0.030), a higher risk of hepatic cirrhosis (P=0.001), and poor differentiation (P=0.028). The 1-, 3-, and 5-year cumulative survival rates for patients within the three groups were as follows: 27.3%, 0%, and 0% for group I, respectively; 62.5%, 30.0%, and 0% for group II, respectively; and 87.5%, 66.7%, and 50.0% for group III, respectively. The results were significantly different in an overall comparison (P=0.000). CONCLUSION: Patients with HBV-associated ICC showed different clinicopathological features and lower survival rates compared to patients with ICC without HBV infection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"excess body weight obesity link gastrointestinal hepatobiliary cancer excess body weight ebw independent risk factor many human malignancies including cancers throughout gastrointestinal hepatobiliary tract esophagus colorectum relative risk gastrointestinal cancer obese individuals approximately 1 5 2 0 times normal weight individuals organ specific gender specific differences specific cancers association ebw risk premalignant stages gastrointestinal carcinogenesis colorectal adenoma barrett esophagus similar implying role ebw early stages carcinogenesis relevant preventative strategies ebw also impacts negatively gastrointestinal cancer outcomes mechanistic basis association ebw carcinogenesis remains incompletely understood postulated mechanisms include increased insulin insulin like growth factor signaling chronic inflammation linked metabolic syndrome well signaling via adipokines leptin role obesity related changes intestinal microbiome gastrointestinal carcinogenesis deserves attention whether weight loss leads reduced future gastrointestinal liver cancer risk yet fully explored support idea weight loss negatively regulates colorectal carcinogenesis addition data suggest reduction risk several cancers first 10 years bariatric surgery pubmed","probabilities":0.8684211,"Title":"Excess body weight and obesity--the link with gastrointestinal and hepatobiliary cancer","Abstract":"Excess body weight (EBW) is an independent risk factor for many human malignancies, including cancers throughout the gastrointestinal and hepatobiliary tract from the esophagus to the colorectum. The relative risk of gastrointestinal cancer in obese individuals is approximately 1.5-2.0 times that for normal weight individuals, with organ-specific and gender-specific differences for specific cancers. The association between EBW and risk of premalignant stages of gastrointestinal carcinogenesis, such as colorectal adenoma and Barrett esophagus, is similar, implying a role for EBW during the early stages of carcinogenesis that could be relevant to preventative strategies. EBW also impacts negatively on gastrointestinal cancer outcomes. The mechanistic basis of the association between EBW and carcinogenesis remains incompletely understood. Postulated mechanisms include increased insulin and insulin-like growth factor signaling and chronic inflammation (both linked to the metabolic syndrome), as well as signaling via adipokines, such as leptin. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention. Whether weight loss leads to reduced future gastrointestinal and liver cancer risk has yet to be fully explored. There is some support for the idea that weight loss negatively regulates colorectal carcinogenesis. In addition, data suggest a reduction in risk of several cancers in the first 10 years after bariatric surgery.","Source":"PubMed","category":"HUMAN","training_data":"Excess body weight and obesity--the link with gastrointestinal and hepatobiliary cancer Excess body weight (EBW) is an independent risk factor for many human malignancies, including cancers throughout the gastrointestinal and hepatobiliary tract from the esophagus to the colorectum. The relative risk of gastrointestinal cancer in obese individuals is approximately 1.5-2.0 times that for normal weight individuals, with organ-specific and gender-specific differences for specific cancers. The association between EBW and risk of premalignant stages of gastrointestinal carcinogenesis, such as colorectal adenoma and Barrett esophagus, is similar, implying a role for EBW during the early stages of carcinogenesis that could be relevant to preventative strategies. EBW also impacts negatively on gastrointestinal cancer outcomes. The mechanistic basis of the association between EBW and carcinogenesis remains incompletely understood. Postulated mechanisms include increased insulin and insulin-like growth factor signaling and chronic inflammation (both linked to the metabolic syndrome), as well as signaling via adipokines, such as leptin. The role of obesity-related changes in the intestinal microbiome in gastrointestinal carcinogenesis deserves further attention. Whether weight loss leads to reduced future gastrointestinal and liver cancer risk has yet to be fully explored. There is some support for the idea that weight loss negatively regulates colorectal carcinogenesis. In addition, data suggest a reduction in risk of several cancers in the first 10 years after bariatric surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic prediction role preoperative serum albumin level patients intahepatic cholangiocarcinoma following hepatectomy background little information regarding role preoperative serum albumin alb intrahepatic cholangiocarcinoma icc patients underwent liver resection methods clinicopathological characteristics survival rate 91 icc patients underwent surgery 2009 2013 included study optimal cut alb determined plotting receiver operating characteristics curves alb predicting overall survival os utilizing youden index long term outcome calculated kaplan meire method results pathological characteristics similar groups 1 3 year disease free survival dfs rates high alb group lower alb group 62 7 vs 25 5 27 0 vs 11 1 respectively p 0 001 1 3 year os rates high alb group lower alb group 78 4 vs 57 5 42 6 vs 6 7 respectively p 0 001 alb level continuous variable multivariate analysis remained favorable factor dfs os p 0 05 furthermore alb distinguish prognoses non cirrhotic patients multivariate analysis showed pathological risk factors like lymph node involvement positive surgical margin satellite lesions carbohydrate antigen 19 9 associated dfs os p 0 05 conclusions higher preoperative serum alb level associated better long term survival icc patients stn","probabilities":0.9799733,"Title":"The Prognostic Prediction Role Of Preoperative Serum Albumin Level In Patients With Intahepatic Cholangiocarcinoma Following Hepatectomy","Abstract":"Background: There is little information regarding the role of preoperative serum albumin (ALB) in intrahepatic cholangiocarcinoma (ICC) patients who underwent liver resection. \r\n\r\n Methods: Clinicopathological characteristics and survival rate of 91 ICC patients who underwent surgery between 2009 and 2013 were included in this study. The optimal cut-off for ALB were determined by plotting the receiver operating characteristics curves of ALB in predicting overall survival (OS) and utilizing the Youden index. Long-term outcome was calculated by Kaplan-meire method. \r\n\r\n Results: The pathological characteristics were similar in both groups. The 1- and 3-year disease-free survival (DFS) rates between the high ALB group and the lower ALB group were 62.7 vs. 25.5% and 27.0 vs. 11.1% respectively (p < 0.001). The 1- and 3-year OS rates between the high ALB group and the lower ALB group were 78.4 vs. 57.5% and 42.6 vs. 6.7% respectively (p < 0.001). The ALB level as continuous variable in multivariate analysis remained a favorable factor for DFS and OS (p < 0.05). Furthermore, ALB could distinguish the prognoses in non-cirrhotic patients. Multivariate analysis showed other pathological risk factors like lymph node involvement, positive surgical margin, satellite lesions, and carbohydrate antigen 19-9 were associated with DFS and OS (p < 0.05 for all). \r\n\r\n Conclusions: A higher preoperative serum ALB level is associated with better long-term survival in ICC patients.","Source":"STN","category":"HUMAN","training_data":"The Prognostic Prediction Role Of Preoperative Serum Albumin Level In Patients With Intahepatic Cholangiocarcinoma Following Hepatectomy Background: There is little information regarding the role of preoperative serum albumin (ALB) in intrahepatic cholangiocarcinoma (ICC) patients who underwent liver resection. \r\n\r\n Methods: Clinicopathological characteristics and survival rate of 91 ICC patients who underwent surgery between 2009 and 2013 were included in this study. The optimal cut-off for ALB were determined by plotting the receiver operating characteristics curves of ALB in predicting overall survival (OS) and utilizing the Youden index. Long-term outcome was calculated by Kaplan-meire method. \r\n\r\n Results: The pathological characteristics were similar in both groups. The 1- and 3-year disease-free survival (DFS) rates between the high ALB group and the lower ALB group were 62.7 vs. 25.5% and 27.0 vs. 11.1% respectively (p < 0.001). The 1- and 3-year OS rates between the high ALB group and the lower ALB group were 78.4 vs. 57.5% and 42.6 vs. 6.7% respectively (p < 0.001). The ALB level as continuous variable in multivariate analysis remained a favorable factor for DFS and OS (p < 0.05). Furthermore, ALB could distinguish the prognoses in non-cirrhotic patients. Multivariate analysis showed other pathological risk factors like lymph node involvement, positive surgical margin, satellite lesions, and carbohydrate antigen 19-9 were associated with DFS and OS (p < 0.05 for all). \r\n\r\n Conclusions: A higher preoperative serum ALB level is associated with better long-term survival in ICC patients. STN","prediction_labels":"HUMAN"},{"cleaned":"increased expression microrna 335 predicts favorable prognosis primary gallbladder carcinoma background micrornas mirnas display aberrant expression patterns functional abnormalities many types cancer however roles primary gallbladder carcinoma pgc well documented mir 335 demonstrated involved tumorigenesis several cancers digestive system aim study investigate clinical significance mir 335 pgc methods mir 335 expression 166 human pgc tissues matched adjacent nondysplastic gallbladder epithelia measured real time quantitative polymerase chain reaction rt pcr assay results expression level mir 335 significantly lower pgc tissues nondysplastic gallbladder epithelia p 0 001 166 pgc patients 96 57 83 reduced expression mir 335 additionally expression mir 335 significantly lower pgc tissues high histologic grade p 0 02 advanced pathologic stage p 0 009 clinical stage p 0 008 positive lymph node metastasis p 0 001 univariate analysis log rank test histologic grade p 0 03 pathologic stage p 0 008 clinical stage p 0 01 lymph node metastasis p 0 001 mir 335 expression p 0 001 significant prognostic factors overall survival pgc patients multivariate analysis revealed pathologic stage p 0 02 lymph node metastasis p 0 008 mir 335 expression p 0 006 maintained independent prognostic influence overall survival conclusion study offers convincing evidence first time mir 335 downregulated majority pgc patients may associated aggressive tumor behaviors loss mir 335 expression may useful marker clinical outcome therapeutic target pgc stn","probabilities":1.0,"Title":"Increased Expression Of Microrna-335 Predicts A Favorable Prognosis In Primary Gallbladder Carcinoma","Abstract":"Background: MicroRNAs (miRNAs) display aberrant expression patterns and functional abnormalities in many types of cancer. However, their roles in primary gallbladder carcinoma (PGC) have not been well documented. miR-335 has been demonstrated to be involved in tumorigenesis of several cancers in the digestive system. The aim of this study was to investigate the clinical significance of miR-335 in PGC. \r\n\r\n Methods: miR-335 expression in 166 human PGC tissues and matched adjacent nondysplastic gallbladder epithelia was measured by real-time quantitative polymerase chain reaction (RT-PCR) assay. \r\n\r\n Results: The expression level of miR-335 was significantly lower in PGC tissues than that in nondysplastic gallbladder epithelia (P<0.001). Of 166 PGC patients, 96 (57.83%) had reduced expression of miR-335. Additionally, the expression of miR-335 was significantly lower in PGC tissues with high histologic grade (P=0.02), advanced pathologic T stage (P=0.009) and clinical stage (P=0.008), and with positive lymph node metastasis (P=0.001). In univariate analysis by log-rank test, histologic grade (P=0.03), pathologic T stage (P=0.008), clinical stage (P=0.01), lymph node metastasis (P<0.001), and miR-335 expression (P<0.001) were significant prognostic factors for overall survival of PGC patients. Multivariate analysis further revealed that pathologic T stage (P=0.02), lymph node metastasis (P=0.008), and miR-335 expression (P=0.006) maintained independent prognostic influence on overall survival. \r\n\r\n Conclusion: This study offers convincing evidence for the first time that miR-335 was downregulated in a majority of PGC patients and may be associated with the aggressive tumor behaviors. Loss of miR-335 expression may be a useful marker for clinical outcome and a therapeutic target for PGC.","Source":"STN","category":"ANIMAL","training_data":"Increased Expression Of Microrna-335 Predicts A Favorable Prognosis In Primary Gallbladder Carcinoma Background: MicroRNAs (miRNAs) display aberrant expression patterns and functional abnormalities in many types of cancer. However, their roles in primary gallbladder carcinoma (PGC) have not been well documented. miR-335 has been demonstrated to be involved in tumorigenesis of several cancers in the digestive system. The aim of this study was to investigate the clinical significance of miR-335 in PGC. \r\n\r\n Methods: miR-335 expression in 166 human PGC tissues and matched adjacent nondysplastic gallbladder epithelia was measured by real-time quantitative polymerase chain reaction (RT-PCR) assay. \r\n\r\n Results: The expression level of miR-335 was significantly lower in PGC tissues than that in nondysplastic gallbladder epithelia (P<0.001). Of 166 PGC patients, 96 (57.83%) had reduced expression of miR-335. Additionally, the expression of miR-335 was significantly lower in PGC tissues with high histologic grade (P=0.02), advanced pathologic T stage (P=0.009) and clinical stage (P=0.008), and with positive lymph node metastasis (P=0.001). In univariate analysis by log-rank test, histologic grade (P=0.03), pathologic T stage (P=0.008), clinical stage (P=0.01), lymph node metastasis (P<0.001), and miR-335 expression (P<0.001) were significant prognostic factors for overall survival of PGC patients. Multivariate analysis further revealed that pathologic T stage (P=0.02), lymph node metastasis (P=0.008), and miR-335 expression (P=0.006) maintained independent prognostic influence on overall survival. \r\n\r\n Conclusion: This study offers convincing evidence for the first time that miR-335 was downregulated in a majority of PGC patients and may be associated with the aggressive tumor behaviors. Loss of miR-335 expression may be a useful marker for clinical outcome and a therapeutic target for PGC. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic factors progression free overall survival advanced biliary tract cancer background biliary tract cancer uncommon cancer poor outcome assembled data national cancer research institute uk abc 02 study 10 international studies determine prognostic outcome characteristics patients advanced disease methods multivariable analyses final dataset abc 02 study carried variables simultaneously included cox proportional hazards model backward elimination used produce final model using significance level 10 selected variables associated independently outcome score validated externally receiver operating curve roc analysis using independent international dataset results total 410 patients included abc 02 study 753 international dataset overall survival os progression free survival pfs cox model derived abc 02 study white blood cells haemoglobin disease status bilirubin neutrophils gender performance status considered prognostic survival p 0 10 patients metastatic disease hazard ratio hr 1 56 95 confidence interval ci 1 20 2 02 eastern cooperative oncology group performance status ecog ps 2 worse survival hr 2 24 95 ci 1 53 3 28 dataset restricted patients received cisplatin gemcitabine ecog ps 0 1 haemoglobin disease status bilirubin neutrophils associated pfs os roc analysis suggested models generated abc 02 study limited prognostic value 6 month pfs area curve auc 62 95 ci 57 68 1 year os auc 64 95 ci 58 69 conclusion data propose set prognostic criteria outcome advanced biliary tract cancer derived abc 02 study validated international dataset although findings establish benchmark prognostic evaluation patients abc confirm value longheld clinical observations ability model correctly predict prognosis limited needs improved identification additional clinical molecular markers pubmed","probabilities":0.9799733,"Title":"Prognostic factors for progression-free and overall survival in advanced biliary tract cancer","Abstract":"BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable analyses of the final dataset from the ABC-02 study were carried out. All variables were simultaneously included in a Cox proportional hazards model, and backward elimination was used to produce the final model (using a significance level of 10%), in which the selected variables were associated independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression-free survival (PFS) Cox model was derived from the ABC-02 study. White blood cells, haemoglobin, disease status, bilirubin, neutrophils, gender, and performance status were considered prognostic for survival (all with P < 0.10). Patients with metastatic disease {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.20-2.02]} and Eastern Cooperative Oncology Group performance status (ECOG PS) 2 had worse survival [HR 2.24 (95% CI 1.53-3.28)]. In a dataset restricted to patients who received cisplatin and gemcitabine with ECOG PS 0 and 1, only haemoglobin, disease status, bilirubin, and neutrophils were associated with PFS and OS. ROC analysis suggested the models generated from the ABC-02 study had a limited prognostic value [6-month PFS: area under the curve (AUC) 62% (95% CI 57-68); 1-year OS: AUC 64% (95% CI 58-69)]. CONCLUSION: These data propose a set of prognostic criteria for outcome in advanced biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict prognosis is limited and needs to be improved through identification of additional clinical and molecular markers.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors for progression-free and overall survival in advanced biliary tract cancer BACKGROUND: Biliary tract cancer is an uncommon cancer with a poor outcome. We assembled data from the National Cancer Research Institute (UK) ABC-02 study and 10 international studies to determine prognostic outcome characteristics for patients with advanced disease. METHODS: Multivariable analyses of the final dataset from the ABC-02 study were carried out. All variables were simultaneously included in a Cox proportional hazards model, and backward elimination was used to produce the final model (using a significance level of 10%), in which the selected variables were associated independently with outcome. This score was validated externally by receiver operating curve (ROC) analysis using the independent international dataset. RESULTS: A total of 410 patients were included from the ABC-02 study and 753 from the international dataset. An overall survival (OS) and progression-free survival (PFS) Cox model was derived from the ABC-02 study. White blood cells, haemoglobin, disease status, bilirubin, neutrophils, gender, and performance status were considered prognostic for survival (all with P < 0.10). Patients with metastatic disease {hazard ratio (HR) 1.56 [95% confidence interval (CI) 1.20-2.02]} and Eastern Cooperative Oncology Group performance status (ECOG PS) 2 had worse survival [HR 2.24 (95% CI 1.53-3.28)]. In a dataset restricted to patients who received cisplatin and gemcitabine with ECOG PS 0 and 1, only haemoglobin, disease status, bilirubin, and neutrophils were associated with PFS and OS. ROC analysis suggested the models generated from the ABC-02 study had a limited prognostic value [6-month PFS: area under the curve (AUC) 62% (95% CI 57-68); 1-year OS: AUC 64% (95% CI 58-69)]. CONCLUSION: These data propose a set of prognostic criteria for outcome in advanced biliary tract cancer derived from the ABC-02 study that are validated in an international dataset. Although these findings establish the benchmark for the prognostic evaluation of patients with ABC and confirm the value of longheld clinical observations, the ability of the model to correctly predict prognosis is limited and needs to be improved through identification of additional clinical and molecular markers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"upregulation retinoic acid receptor reverses drug resistance cholangiocarcinoma cells enhancing susceptibility apoptosis retinoic acid receptor rar known tumor suppressor gene frequently silenced numerous malignant types tumor recent reports demonstrated loss rar expression may responsible part drug resistance observed clinical trials however little known role rar regulating drug sensitivity patients cholangiocarcinoma cca high risk mortality poor outcomes present study low rar expression observed majority cca tissues investigated 28 33 84 8 addition cca cell line qbc939 exhibits low rar expression found significantly resistant chemotherapeutic agents compared sk cha 1 mz cha 1 hccc9810 cca cell lines exhibit high rar expression furthermore upregulation rar significantly enhanced sensitivity qbc939 cells common chemotherapeutic agents vitro vivo upregulation rar shown increase expression proapoptotic genes bax bak bim addition caspase 3 activity decrease expression antiapoptotic genes bcl 2 bcl xl mcl 1 result cca cells susceptible caspase dependent apoptosis taken together data suggest rar upregulation rendered cca cells sensitive chemotherapeutic agents increasing susceptibility cells caspase dependent apoptosis results support hypothesis rar may ideal chemosensitization target treatment patients drug resistant cca stn","probabilities":1.0,"Title":"Upregulation Of Retinoic Acid Receptor-ß Reverses Drug Resistance In Cholangiocarcinoma Cells By Enhancing Susceptibility To Apoptosis","Abstract":"Retinoic acid receptor β (RARβ), a known tumor suppressor gene, is frequently silenced in numerous malignant types of tumor. Recent reports have demonstrated that loss of RARβ expression may be responsible, in part, for the drug resistance observed in clinical trials. However, little is known about the role of RARβ in regulating drug sensitivity in patients with cholangiocarcinoma (CCA) with a high risk of mortality and poor outcomes. In the present study, low RARβ expression was observed in the majority of CCA tissues investigated (28/33, 84.8%). In addition, the CCA cell line QBC939, which exhibits low RARβ expression, was found to be significantly resistant to chemotherapeutic agents compared with SK‑ChA‑1, MZ‑ChA‑1 and Hccc9810 CCA cell lines, which exhibit high RARβ expression. Furthermore, upregulation of RARβ significantly enhanced the sensitivity of QBC939 cells to common chemotherapeutic agents both in vitro and in vivo. Upregulation of RARβ was shown to increase the expression of proapoptotic genes bax, bak and bim, in addition to caspase‑3 activity, and decrease the expression of antiapoptotic genes bcl‑2, bcl‑xL and mcl‑1. As a result, CCA cells were more susceptible to caspase‑dependent apoptosis. Taken together, these data suggest that RARβ upregulation rendered CCA cells more sensitive to chemotherapeutic agents by increasing the susceptibility of cells to caspase-dependent apoptosis. These results support the hypothesis that RARβ may be an ideal chemosensitization target for the treatment of patients with drug-resistant CCA.","Source":"STN","category":"ANIMAL","training_data":"Upregulation Of Retinoic Acid Receptor-ß Reverses Drug Resistance In Cholangiocarcinoma Cells By Enhancing Susceptibility To Apoptosis Retinoic acid receptor β (RARβ), a known tumor suppressor gene, is frequently silenced in numerous malignant types of tumor. Recent reports have demonstrated that loss of RARβ expression may be responsible, in part, for the drug resistance observed in clinical trials. However, little is known about the role of RARβ in regulating drug sensitivity in patients with cholangiocarcinoma (CCA) with a high risk of mortality and poor outcomes. In the present study, low RARβ expression was observed in the majority of CCA tissues investigated (28/33, 84.8%). In addition, the CCA cell line QBC939, which exhibits low RARβ expression, was found to be significantly resistant to chemotherapeutic agents compared with SK‑ChA‑1, MZ‑ChA‑1 and Hccc9810 CCA cell lines, which exhibit high RARβ expression. Furthermore, upregulation of RARβ significantly enhanced the sensitivity of QBC939 cells to common chemotherapeutic agents both in vitro and in vivo. Upregulation of RARβ was shown to increase the expression of proapoptotic genes bax, bak and bim, in addition to caspase‑3 activity, and decrease the expression of antiapoptotic genes bcl‑2, bcl‑xL and mcl‑1. As a result, CCA cells were more susceptible to caspase‑dependent apoptosis. Taken together, these data suggest that RARβ upregulation rendered CCA cells more sensitive to chemotherapeutic agents by increasing the susceptibility of cells to caspase-dependent apoptosis. These results support the hypothesis that RARβ may be an ideal chemosensitization target for the treatment of patients with drug-resistant CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"expression serum survivin protein diagnosis prognosis gallbladder cancer comparative study role survivin gallbladder cancer gbc evaluated investigated survivin protein expression serum patients gallbladder diseases cholelithiasis n 30 gbc n 39 compared healthy controls n 25 clinicopathological parameters diagnosis prognosis patients gbc correlated expression serum survivin enzyme linked immunosorbent assay significantly higher p 0 0001 expression survivin protein observed gbc compared cholelithiasis control increased survivin expression significantly associated higher tumor stage stage iii vs stage ii p 0 0001 cellular differentiation poor moderate vs well differentiated p 0 0001 gbc significant correlation observed clinico pathological parameters studied cutoff value survivin protein 79 pg ml sensitivity 81 16 specificity 80 differentiated diseased group cholelithiasis gbc control group cutoff value 109 pg ml differentiated gbc cholelithiasis sensitivity 82 05 specificity 93 33 though significant increased expression survivin associated median overall survival 12 vs 18 months p 0 05 gbc patients study suggests survivin protein serum useful diagnostic marker important prognostic factor gbc pubmed","probabilities":0.9799733,"Title":"Expression of serum survivin protein in diagnosis and prognosis of gallbladder cancer: a comparative study","Abstract":"The role of survivin in gallbladder cancer (GBC) has not been evaluated. We investigated survivin protein expression in serum of patients with gallbladder diseases (cholelithiasis, n = 30; GBC, n = 39) and compared with healthy controls (n = 25). Clinicopathological parameters, diagnosis and prognosis of patients with GBC were correlated with the expression of serum survivin by enzyme-linked immunosorbent assay. Significantly higher (P < 0.0001) expression of survivin protein was observed in GBC as compared to cholelithiasis and control. Increased survivin expression was significantly associated with higher tumor stage (stage III vs. stage II; P < 0.0001) and cellular differentiation (poor and moderate vs. well differentiated; P < 0.0001) in GBC. No significant correlation was observed with any of the other clinico-pathological parameters studied. The cutoff value of survivin protein of 79 pg/ml with sensitivity of 81.16 % and specificity of 80 % differentiated the diseased group (cholelithiasis or GBC) from control group were as the cutoff value of 109 pg/ml differentiated GBC from cholelithiasis with a sensitivity of 82.05 % and specificity of 93.33 %. Though not significant, increased expression of survivin was associated with median overall survival (12 vs. 18 months; P = 0.05) in GBC patients. Our study suggests that survivin protein in serum could be both a useful diagnostic marker and an important prognostic factor for GBC.","Source":"PubMed","category":"HUMAN","training_data":"Expression of serum survivin protein in diagnosis and prognosis of gallbladder cancer: a comparative study The role of survivin in gallbladder cancer (GBC) has not been evaluated. We investigated survivin protein expression in serum of patients with gallbladder diseases (cholelithiasis, n = 30; GBC, n = 39) and compared with healthy controls (n = 25). Clinicopathological parameters, diagnosis and prognosis of patients with GBC were correlated with the expression of serum survivin by enzyme-linked immunosorbent assay. Significantly higher (P < 0.0001) expression of survivin protein was observed in GBC as compared to cholelithiasis and control. Increased survivin expression was significantly associated with higher tumor stage (stage III vs. stage II; P < 0.0001) and cellular differentiation (poor and moderate vs. well differentiated; P < 0.0001) in GBC. No significant correlation was observed with any of the other clinico-pathological parameters studied. The cutoff value of survivin protein of 79 pg/ml with sensitivity of 81.16 % and specificity of 80 % differentiated the diseased group (cholelithiasis or GBC) from control group were as the cutoff value of 109 pg/ml differentiated GBC from cholelithiasis with a sensitivity of 82.05 % and specificity of 93.33 %. Though not significant, increased expression of survivin was associated with median overall survival (12 vs. 18 months; P = 0.05) in GBC patients. Our study suggests that survivin protein in serum could be both a useful diagnostic marker and an important prognostic factor for GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"helicobacter pylori infection associated cholangiocarcinoma risk meta analysis published case control cohort studies introduction since discovery helicobacter pylori human biliary system association helicobacter pylori infection cholangiocarcinoma debate observational studies inconsistently reported relationship h pylori infection risk biliary tract cancer meta analysis conducted published case control cohort studies explore quantify association methods literature search carried identify eligible articles june 2016 overall meta analysis included studies subgroup analysis performed based regional distribution subgroup analysis light detection methods specimens also conducted studies overall hepatobiliary carcinoma excluded well studies without full text random effects model assigned compute summary point estimates corresponding 95 confidence intervals cis subgroup meta regression analyses also performed explore sources heterogeneity results 4 case control studies included subgroup analysis showed pcr effective efficient method detect helicobacter species surgically resected tissue bile overall meta analysis favor significant association helicobacter pylori infection cholangiocarcinoma cumulative 0 82 95 ci 0 57 1 18 p 0 29 subgroup analysis based geographic distribution indicated prevalence h pylori infection cholangiocarcinoma patients 96 6 usa thailand 55 2 mexico 75 japan 83 3 overall prevalence 73 8 significant heterogeneity among studies obvious publication bias conclusion study support possible association helicobacter pylori infection cholangiocarcinoma insufficient evidence conclude relationship h pylori infection risk cholangiocarcinoma future prospective studies h pylori infection malignancy needed google scholar","probabilities":0.8684211,"Title":"Is Helicobacter Pylori Infection Associated With Cholangiocarcinoma Risk? A Meta-Analysis Of Published Case-Control And Cohort Studies","Abstract":"Introduction: Since the discovery of Helicobacter pylori in human biliary system, the association between Helicobacter pylori infection and cholangiocarcinoma is under debate. Observational studies inconsistently reported the relationship between H. pylori infection and risk of biliary tract cancer. This meta-analysis was conducted of published case-control and cohort studies to explore and quantify the association.\nMethods: Literature search was carried out to identify all eligible articles through June of 2016. Overall meta-analysis of all included studies and subgroup analysis was performed based on regional distribution. Subgroup analysis in the light of detection methods and specimens was also conducted. Studies on overall hepatobiliary carcinoma were excluded, as well as studies without full text. A random-effects model was assigned to compute summary point estimates with corresponding 95% confidence intervals (CIs). Subgroup and meta-regression analyses were also performed to explore sources of heterogeneity.\nResults: 4 case-control studies were included. The subgroup analysis showed that PCR was the most effective and efficient method to detect Helicobacter species in surgically resected tissue and bile. Overall meta-analysis did not favor a significant association between Helicobacter pylori infection and cholangiocarcinoma (cumulative OR 0.82, 95% CI 0.57 to 1.18, P=0.29). Subgroup analysis based on geographic distribution indicated that the prevalence of H. pylori infection in cholangiocarcinoma patients was 96.6% in USA, in Thailand 55.2%, in Mexico 75%, in Japan 83.3%, with overall prevalence 73.8%. There was significant heterogeneity among studies and obvious publication bias.\nConclusion: This study does not support possible association between Helicobacter pylori infection and cholangiocarcinoma. There is insufficient evidence to conclude any relationship between H. pylori infection and risk of cholangiocarcinoma. Future prospective studies of H. pylori infection and this malignancy are needed.","Source":"Google Scholar","category":"HUMAN","training_data":"Is Helicobacter Pylori Infection Associated With Cholangiocarcinoma Risk? A Meta-Analysis Of Published Case-Control And Cohort Studies Introduction: Since the discovery of Helicobacter pylori in human biliary system, the association between Helicobacter pylori infection and cholangiocarcinoma is under debate. Observational studies inconsistently reported the relationship between H. pylori infection and risk of biliary tract cancer. This meta-analysis was conducted of published case-control and cohort studies to explore and quantify the association.\nMethods: Literature search was carried out to identify all eligible articles through June of 2016. Overall meta-analysis of all included studies and subgroup analysis was performed based on regional distribution. Subgroup analysis in the light of detection methods and specimens was also conducted. Studies on overall hepatobiliary carcinoma were excluded, as well as studies without full text. A random-effects model was assigned to compute summary point estimates with corresponding 95% confidence intervals (CIs). Subgroup and meta-regression analyses were also performed to explore sources of heterogeneity.\nResults: 4 case-control studies were included. The subgroup analysis showed that PCR was the most effective and efficient method to detect Helicobacter species in surgically resected tissue and bile. Overall meta-analysis did not favor a significant association between Helicobacter pylori infection and cholangiocarcinoma (cumulative OR 0.82, 95% CI 0.57 to 1.18, P=0.29). Subgroup analysis based on geographic distribution indicated that the prevalence of H. pylori infection in cholangiocarcinoma patients was 96.6% in USA, in Thailand 55.2%, in Mexico 75%, in Japan 83.3%, with overall prevalence 73.8%. There was significant heterogeneity among studies and obvious publication bias.\nConclusion: This study does not support possible association between Helicobacter pylori infection and cholangiocarcinoma. There is insufficient evidence to conclude any relationship between H. pylori infection and risk of cholangiocarcinoma. Future prospective studies of H. pylori infection and this malignancy are needed. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cross sectional study potential transmission carcinogenic liver fluke opisthorchis viverrini fishborne zoonotic trematodes aquaculture fish throughout southeast asia china eating raw partially cooked cyprinid fish causes liver hepatobiliary disease cancer cholangiocarcinoma due fishborne zoonotic trematodes fzt particular clonorchis sinensis opisthorchis viverrini primary source transmission native fish aquaculture fish also reported high infective potential cross sectional survey fzt fish farms conducted endemic area khon kaen province thailand using conventional polymerase chain reaction pcr methods detected o viverrini fzt metacercariae centrocestus formosanus haplorchis taichui two popular fish species barbonymus gonionotus silver barb cirrhinus mrigala mrigal aquaculture farms species infected five six farms examined pcr conventional methods yet prevalence fzt metacercariae aquaculture fish high 46 9 addition o viverrini 17 1 native fish cyclocheilichthys armatus hampala dispar prevalence fzt 81 4 included 5 7 c formosanus 17 1 h taichui conventional method knowledge first discovery o viverrini aquaculture fish thailand comprehensive studies required determine human induced disease transmission coupled natural transmission cycle occurs throughout aquaculture industry region significant impact food quality safety provides basis development effective strategy prevention control foodborne diseases pubmed","probabilities":0.8684211,"Title":"A cross-sectional study on the potential transmission of the carcinogenic liver fluke Opisthorchis viverrini and other fishborne zoonotic trematodes by aquaculture fish","Abstract":"Throughout Southeast Asia and China, eating raw and or partially cooked cyprinid fish causes liver (hepatobiliary) disease and cancer (cholangiocarcinoma) due to fishborne zoonotic trematodes (FZT), in particular Clonorchis sinensis and Opisthorchis viverrini. The primary source of transmission is by native fish, but aquaculture fish are also reported to have high infective potential. Here, a cross-sectional survey of FZT in fish farms was conducted in an endemic area in Khon Kaen Province, Thailand. By using conventional and polymerase chain reaction (PCR) methods, we detected O. viverrini and FZT metacercariae (Centrocestus formosanus and Haplorchis taichui) in two popular fish species, Barbonymus gonionotus (silver barb) and Cirrhinus mrigala (mrigal), from aquaculture farms. Both species were infected in five of six farms examined by PCR but not by conventional methods, yet the prevalence of FZT metacercariae in aquaculture fish was high (46.9%). In addition to O. viverrini (17.1%), the native fish Cyclocheilichthys armatus and Hampala dispar had a prevalence of FZT of 81.4%, which included 5.7% for C. formosanus and 17.1% for H. taichui by conventional method. To our knowledge, this is the first discovery of O. viverrini in aquaculture fish in Thailand. More comprehensive studies are required to determine if human-induced disease transmission coupled with natural transmission cycle occurs throughout the aquaculture industry in the region. This has significant impact on food quality and safety, and provides the basis for the development of an effective strategy for the prevention and control of foodborne diseases.","Source":"PubMed","category":"ANIMAL","training_data":"A cross-sectional study on the potential transmission of the carcinogenic liver fluke Opisthorchis viverrini and other fishborne zoonotic trematodes by aquaculture fish Throughout Southeast Asia and China, eating raw and or partially cooked cyprinid fish causes liver (hepatobiliary) disease and cancer (cholangiocarcinoma) due to fishborne zoonotic trematodes (FZT), in particular Clonorchis sinensis and Opisthorchis viverrini. The primary source of transmission is by native fish, but aquaculture fish are also reported to have high infective potential. Here, a cross-sectional survey of FZT in fish farms was conducted in an endemic area in Khon Kaen Province, Thailand. By using conventional and polymerase chain reaction (PCR) methods, we detected O. viverrini and FZT metacercariae (Centrocestus formosanus and Haplorchis taichui) in two popular fish species, Barbonymus gonionotus (silver barb) and Cirrhinus mrigala (mrigal), from aquaculture farms. Both species were infected in five of six farms examined by PCR but not by conventional methods, yet the prevalence of FZT metacercariae in aquaculture fish was high (46.9%). In addition to O. viverrini (17.1%), the native fish Cyclocheilichthys armatus and Hampala dispar had a prevalence of FZT of 81.4%, which included 5.7% for C. formosanus and 17.1% for H. taichui by conventional method. To our knowledge, this is the first discovery of O. viverrini in aquaculture fish in Thailand. More comprehensive studies are required to determine if human-induced disease transmission coupled with natural transmission cycle occurs throughout the aquaculture industry in the region. This has significant impact on food quality and safety, and provides the basis for the development of an effective strategy for the prevention and control of foodborne diseases. PubMed","prediction_labels":"HUMAN"},{"cleaned":"indications major hepatectomy combined procedures advanced gallbladder cancer background clinical impact major hepatectomy advanced gallbladder cancer currently unclear methods patients underwent resection stage ii iii iv gallbladder cancer enrolled surgical outcomes patients underwent major hepatectomy compared patients treated minor hepatectomy unresectable gallbladder cancer clinical impact major hepatectomy combined advanced procedures portal vein resection pancreatoduodenectomy advanced gallbladder cancer evaluated results total 96 patients enrolled 29 patients underwent major 67 minor hepatectomy overall morbidity rate higher major hepatectomy group 55 versus 27 per cent p 0 022 deaths major hepatectomy overall survival better major hepatectomy group group 15 patients unresectable disease median survival 17 7 versus 11 4 months p 0 003 subgroup analysis major hepatectomy group liver metastasis p 0 038 hepatic arterial invasion p 0 017 independently associated overall survival overall survival patients liver metastasis p 0 572 hepatic arterial invasion p 0 776 comparable unresectable group however overall survival among patients lymph node metastasis p 0 062 following portal vein resection p 0 054 pancreatoduodenectomy p 0 011 better unresectable group conclusion major hepatectomy combined portal vein resection pancreatoduodenectomy necessary may considered treatment advanced gallbladder cancer especially selected patients without liver metastasis hepatic arterial invasion pubmed","probabilities":0.9799733,"Title":"Indications for major hepatectomy and combined procedures for advanced gallbladder cancer","Abstract":"BACKGROUND: The clinical impact of major hepatectomy for advanced gallbladder cancer is currently unclear. METHODS: Patients who underwent resection for stage II, III or IV gallbladder cancer were enrolled. The surgical outcomes of patients who underwent major hepatectomy were compared with those of patients treated with minor hepatectomy and those with unresectable gallbladder cancer. The clinical impact of major hepatectomy and combined advanced procedures such as portal vein resection or pancreatoduodenectomy for advanced gallbladder cancer were evaluated. RESULTS: A total of 96 patients were enrolled; 29 patients underwent major and 67 had minor hepatectomy. The overall morbidity rate was higher in the major hepatectomy group (55 versus 27 per cent; P = 0·022). There were no deaths after major hepatectomy. Overall survival was better in the major hepatectomy group than in the group of 15 patients with unresectable disease (median survival 17·7 versus 11·4 months; P = 0·003). In a subgroup analysis of the major hepatectomy group, liver metastasis (P = 0·038) and hepatic arterial invasion (P = 0·017) were independently associated with overall survival. Overall survival in patients with liver metastasis (P = 0·572) or hepatic arterial invasion (P = 0·776) was comparable with that in the unresectable group. However, overall survival among patients with lymph node metastasis (P = 0·062) or following portal vein resection (P = 0·054) or pancreatoduodenectomy (P = 0·011) was better than in the unresectable group. CONCLUSION: Major hepatectomy combined with portal vein resection or pancreatoduodenectomy, if necessary, may be considered in the treatment of advanced gallbladder cancer, especially in selected patients without liver metastasis or hepatic arterial invasion.","Source":"PubMed","category":"HUMAN","training_data":"Indications for major hepatectomy and combined procedures for advanced gallbladder cancer BACKGROUND: The clinical impact of major hepatectomy for advanced gallbladder cancer is currently unclear. METHODS: Patients who underwent resection for stage II, III or IV gallbladder cancer were enrolled. The surgical outcomes of patients who underwent major hepatectomy were compared with those of patients treated with minor hepatectomy and those with unresectable gallbladder cancer. The clinical impact of major hepatectomy and combined advanced procedures such as portal vein resection or pancreatoduodenectomy for advanced gallbladder cancer were evaluated. RESULTS: A total of 96 patients were enrolled; 29 patients underwent major and 67 had minor hepatectomy. The overall morbidity rate was higher in the major hepatectomy group (55 versus 27 per cent; P = 0·022). There were no deaths after major hepatectomy. Overall survival was better in the major hepatectomy group than in the group of 15 patients with unresectable disease (median survival 17·7 versus 11·4 months; P = 0·003). In a subgroup analysis of the major hepatectomy group, liver metastasis (P = 0·038) and hepatic arterial invasion (P = 0·017) were independently associated with overall survival. Overall survival in patients with liver metastasis (P = 0·572) or hepatic arterial invasion (P = 0·776) was comparable with that in the unresectable group. However, overall survival among patients with lymph node metastasis (P = 0·062) or following portal vein resection (P = 0·054) or pancreatoduodenectomy (P = 0·011) was better than in the unresectable group. CONCLUSION: Major hepatectomy combined with portal vein resection or pancreatoduodenectomy, if necessary, may be considered in the treatment of advanced gallbladder cancer, especially in selected patients without liver metastasis or hepatic arterial invasion. PubMed","prediction_labels":"HUMAN"},{"cleaned":"risk factors gallbladder cancer cholangiocarcinoma similarities differences updates introduction far ranging variation incidence gallbladder cancer gbc cholangiocarcinoma cca different geographic regions globe may reflect risk factor distribution tumors methods authors give comprehensive review known risk factors gbc cca analyze similarities differences risk factors two main types biliary cancer discussion conclusion leading risk factors gbc include gallstones female gender advancing age primary sclerosing cholangitis nitrosamine exposure choledochal cysts clonorchis sinensis opisthorchis viverrini represent important risk factors cca although specific risk factor identified many patients cancers affect mostly individuals sixth decade older cca male predominance gbc predilection females although current level understanding molecular pathogenesis gbc cca interface specific risk factors significantly lower gastrointestinal malignancies continues evolve may soon open new avenues therapy biliary cancers pubmed","probabilities":0.9799733,"Title":"Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates","Abstract":"INTRODUCTION: Far-ranging variation in the incidence of gallbladder cancer (GBC) and cholangiocarcinoma (CCA) in different geographic regions on the globe may reflect the risk factor distribution for these tumors METHODS: The authors give a comprehensive review on the known risk factors for GBC and CCA, and analyze both similarities and differences between the risk factors for the two main types of biliary cancer DISCUSSION AND CONCLUSION: Leading risk factors for GBC include gallstones, female gender, and advancing age. Primary sclerosing cholangitis, nitrosamine exposure, choledochal cysts, Clonorchis sinensis and Opisthorchis viverrini represent important risk factors for CCA, although a specific risk factor cannot be identified for many patients. While both cancers affect mostly individuals in their sixth decade or older, CCA has a male predominance and GBC--a predilection for females. Although the current level of understanding of the molecular pathogenesis of GBC and CCA at the interface with specific risk factors is significantly lower than for other gastrointestinal malignancies, it continues to evolve and may soon open new avenues for the therapy of biliary cancers.","Source":"PubMed","category":"HUMAN","training_data":"Risk factors for gallbladder cancer and cholangiocarcinoma: similarities, differences and updates INTRODUCTION: Far-ranging variation in the incidence of gallbladder cancer (GBC) and cholangiocarcinoma (CCA) in different geographic regions on the globe may reflect the risk factor distribution for these tumors METHODS: The authors give a comprehensive review on the known risk factors for GBC and CCA, and analyze both similarities and differences between the risk factors for the two main types of biliary cancer DISCUSSION AND CONCLUSION: Leading risk factors for GBC include gallstones, female gender, and advancing age. Primary sclerosing cholangitis, nitrosamine exposure, choledochal cysts, Clonorchis sinensis and Opisthorchis viverrini represent important risk factors for CCA, although a specific risk factor cannot be identified for many patients. While both cancers affect mostly individuals in their sixth decade or older, CCA has a male predominance and GBC--a predilection for females. Although the current level of understanding of the molecular pathogenesis of GBC and CCA at the interface with specific risk factors is significantly lower than for other gastrointestinal malignancies, it continues to evolve and may soon open new avenues for the therapy of biliary cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumor location stratify survival patients undergoing resection gallbladder cancer background residual disease rd definitive resection incidental gallbladder cancer igbca influences outcome clinical relevance respect anatomic site incompletely characterized study design consecutive patients igbca undergoing re exploration 1998 2009 identified submitted complete resection analyzed demographics tumor treatment related variables correlated rd survival cancer specific survival stratified site rd local gallbladder bed regional bile duct lymph nodes distant discontiguous liver port site peritoneal results 135 patients submitted re exploration rd found 82 61 overall 63 54 116 patients submitted resection common site regional n 27 43 stage gallbladder specimen independent predictor rd t1b 35 7 t2 48 3 t3 70 p 0 015 presence rd site dramatically reduced median disease free survival dfs 11 2 vs 93 4 months p 0 0001 disease specific survival dss 25 2 months vs reached p 0 0001 compared rd respectively disease specific survival differ according rd location anatomic sites equally poor p 0 87 residual disease site predicted dfs hazard ratio hr 3 3 95 ci 1 9 5 7 p 0 0003 dss hr 2 4 95 ci 1 2 4 6 p 0 01 independent tumor related variables conclusions survival patients rd local regional sites significantly different seen stage iv disease neither subgroup clearly benefiting reoperation outcomes poor patients rd regardless location stn","probabilities":0.9799733,"Title":"Tumor Location Does Not Stratify Survival In Patients Undergoing Resection For Gallbladder Cancer","Abstract":"Background: Residual disease (RD) at definitive resection of incidental gallbladder cancer (IGBCA) influences outcome, but its clinical relevance with respect to anatomic site is incompletely characterized. \r\n\r\n Study design: Consecutive patients with IGBCA undergoing re-exploration from 1998 to 2009 were identified; those submitted to a complete resection were analyzed. Demographics and tumor- and treatment-related variables were correlated with RD and survival. Cancer-specific survival was stratified by site of RD (local [gallbladder bed]; regional [bile duct, lymph nodes]; distant [discontiguous liver, port site, peritoneal]). \r\n\r\n Results: Of the 135 patients submitted to re-exploration, RD was found in 82 (61%) overall and in 63 (54%) of 116 patients submitted to resection; the most common site was regional (n = 27, 43%). The T stage of the gallbladder specimen was the only independent predictor of RD (T1b = 35.7%, T2 = 48.3%, T3 = 70%, p = 0.015). The presence of RD at any site dramatically reduced median disease-free survival (DFS) (11.2 vs 93.4 months, p < 0.0001) and disease-specific survival (DSS) (25.2 months vs not reached, p < 0.0001) compared with no RD, respectively. Disease-specific survival did not differ according to RD location, with all anatomic sites being equally poor (p = 0.87). Residual disease at any site predicted DFS (hazard ratio [HR] 3.3, 95% CI 1.9 to 5.7, p = 0.0003) and DSS (HR 2.4, 95% CI 1.2 to 4.6, p = 0.01), independent of all other tumor-related variables. \r\n\r\n Conclusions: Survival in patients with RD at local or regional sites was not significantly different than that seen in stage IV disease, with neither subgroup clearly benefiting from reoperation. Outcomes were poor in all patients with RD, regardless of location.","Source":"STN","category":"HUMAN","training_data":"Tumor Location Does Not Stratify Survival In Patients Undergoing Resection For Gallbladder Cancer Background: Residual disease (RD) at definitive resection of incidental gallbladder cancer (IGBCA) influences outcome, but its clinical relevance with respect to anatomic site is incompletely characterized. \r\n\r\n Study design: Consecutive patients with IGBCA undergoing re-exploration from 1998 to 2009 were identified; those submitted to a complete resection were analyzed. Demographics and tumor- and treatment-related variables were correlated with RD and survival. Cancer-specific survival was stratified by site of RD (local [gallbladder bed]; regional [bile duct, lymph nodes]; distant [discontiguous liver, port site, peritoneal]). \r\n\r\n Results: Of the 135 patients submitted to re-exploration, RD was found in 82 (61%) overall and in 63 (54%) of 116 patients submitted to resection; the most common site was regional (n = 27, 43%). The T stage of the gallbladder specimen was the only independent predictor of RD (T1b = 35.7%, T2 = 48.3%, T3 = 70%, p = 0.015). The presence of RD at any site dramatically reduced median disease-free survival (DFS) (11.2 vs 93.4 months, p < 0.0001) and disease-specific survival (DSS) (25.2 months vs not reached, p < 0.0001) compared with no RD, respectively. Disease-specific survival did not differ according to RD location, with all anatomic sites being equally poor (p = 0.87). Residual disease at any site predicted DFS (hazard ratio [HR] 3.3, 95% CI 1.9 to 5.7, p = 0.0003) and DSS (HR 2.4, 95% CI 1.2 to 4.6, p = 0.01), independent of all other tumor-related variables. \r\n\r\n Conclusions: Survival in patients with RD at local or regional sites was not significantly different than that seen in stage IV disease, with neither subgroup clearly benefiting from reoperation. Outcomes were poor in all patients with RD, regardless of location. STN","prediction_labels":"HUMAN"},{"cleaned":"capecitabine combined gemcitabine patients advanced biliary tract carcinoma aims background abc 02 trial defined standard therapy patients advanced biliary tract cancer abc however outcome unselected patient population uk described aimed investigate outcome series patients abc two large uk cancer networks methods study design retrospectively reviewed cases abc presenting two uk cancer networks nine year period overall survival os factors influencing os assessed results four hundred two patients available analysis median os 6 2 months univariate analysis age 70 years p 0 047 advanced disease stage p 0 001 gall bladder primary p 0 033 poor performance status p 0 001 lack chemotherapy p 0 001 associated worse outcome survival superior 36 4 patients received palliative chemotherapy 12 5 vs 4 3 months p 0 001 multivariate analysis patients chemotherapy receive fluoropyrimidine based regimens hr 5 12 p 0 022 gemcitabine based regimens hr 5 01 p 0 021 higher mortality whereas effect platinum containing regimens borderline significance hr 2 23 p 0 086 sites age multi agent regimens significant conclusions one largest retrospective studies reporting outcome palliative chemotherapy abc confirms benefit palliative chemotherapy unselected group patients fluoropyrimidine based regimens appear effective gemcitabine based treatments stn","probabilities":0.9799733,"Title":"Capecitabine Combined With Gemcitabine In Patients With Advanced Biliary Tract Carcinoma","Abstract":"Aims and background: The ABC-02 trial has defined the standard therapy for patients with advanced biliary tract cancer (ABC); however, outcome in an unselected patient population in the UK has not been described. We aimed to investigate the outcome of a series of patients with ABC from two large UK cancer networks. \r\n\r\n Methods and study design: We retrospectively reviewed all cases of ABC presenting to two UK cancer networks over a nine-year period. Overall survival (OS) and factors influencing OS were assessed. \r\n\r\n Results: Four hundred and two patients were available for analysis. The median OS was 6.2 months. On univariate analysis, age ≥70 years (P = 0.047), advanced disease stage (P <0.001), gall bladder primary (P = 0.033), poor performance status (P <0.001) and lack of chemotherapy (P <0.001) were associated with worse outcome. Survival was superior in the 36.4% of patients who received palliative chemotherapy (12.5 vs 4.3 months; P <0.001). On multivariate analysis of patients who had chemotherapy, those who did not receive fluoropyrimidine-based regimens (HR = 5.12; P = 0.022) or gemcitabine-based regimens (HR = 5.01; P = 0.021) had a higher mortality, whereas the effect of platinum-containing regimens was of borderline significance (HR = 2.23; P = 0.086). Sites, age, and multi-agent regimens were not significant. \r\n\r\n Conclusions: This is one of the largest retrospective studies reporting outcome of palliative chemotherapy for ABC. It confirms the benefit of palliative chemotherapy in an unselected group of patients. Fluoropyrimidine-based regimens appear to be as effective as gemcitabine-based treatments.","Source":"STN","category":"HUMAN","training_data":"Capecitabine Combined With Gemcitabine In Patients With Advanced Biliary Tract Carcinoma Aims and background: The ABC-02 trial has defined the standard therapy for patients with advanced biliary tract cancer (ABC); however, outcome in an unselected patient population in the UK has not been described. We aimed to investigate the outcome of a series of patients with ABC from two large UK cancer networks. \r\n\r\n Methods and study design: We retrospectively reviewed all cases of ABC presenting to two UK cancer networks over a nine-year period. Overall survival (OS) and factors influencing OS were assessed. \r\n\r\n Results: Four hundred and two patients were available for analysis. The median OS was 6.2 months. On univariate analysis, age ≥70 years (P = 0.047), advanced disease stage (P <0.001), gall bladder primary (P = 0.033), poor performance status (P <0.001) and lack of chemotherapy (P <0.001) were associated with worse outcome. Survival was superior in the 36.4% of patients who received palliative chemotherapy (12.5 vs 4.3 months; P <0.001). On multivariate analysis of patients who had chemotherapy, those who did not receive fluoropyrimidine-based regimens (HR = 5.12; P = 0.022) or gemcitabine-based regimens (HR = 5.01; P = 0.021) had a higher mortality, whereas the effect of platinum-containing regimens was of borderline significance (HR = 2.23; P = 0.086). Sites, age, and multi-agent regimens were not significant. \r\n\r\n Conclusions: This is one of the largest retrospective studies reporting outcome of palliative chemotherapy for ABC. It confirms the benefit of palliative chemotherapy in an unselected group of patients. Fluoropyrimidine-based regimens appear to be as effective as gemcitabine-based treatments. STN","prediction_labels":"HUMAN"},{"cleaned":"incidence subsequent cholangiocarcinomas another malignancy cholangiocarcinoma cca characterized late diagnosis poor outcomes represents commonest malignancy biliary tract understanding metachronous cancer associations may achieve earlier detection aimed evaluate risk subsequent ccas among common cancer survivors national cancer institute surveillance epidemiology end results database 1973 2010 reviewed patients 1 25 primary cancers standardized incidence ratios sirs calculated approximation relative risk subsequent ccas primary malignancy data stratified age primary cancer diagnosis latency period application radiation total 1487 patients developed subsequent ccas patients diagnosed primary cancers ages 20 39 years risk increased among colon sir 14 65 gallbladder 129 29 uterus 7 29 cancer survivors ages 40 59 years oral cavity pharynx 1 89 stomach 3 24 colon 1 76 gallbladder 11 78 lung cancers 1 75 associated increased risk found persistently elevated sirs colon gallbladder cancer ages 60 79 years sir remained significant among gallbladder cancer survivors diagnosed 80 years gallbladder cancer showed elevated risk latency periods except first 6 11 months increased risk lung cancer 1 66 detected 120 months however radiation therapy contribute increased risk population based study suggests several initial cancers associated elevated risk cca increased risk may due shared genetic environmental etiological factors malignancies lower threshold cca surveillance may warranted high risk patients google scholar","probabilities":0.9799733,"Title":"Incidence Of Subsequent Cholangiocarcinomas After Another Malignancy","Abstract":"Cholangiocarcinoma (CCA) characterized by late diagnosis and poor outcomes represents the commonest malignancy of biliary tract. Understanding metachronous cancer associations may achieve earlier detection. We aimed to evaluate the risk of subsequent CCAs among common cancer survivors.\nThe National Cancer Institute's Surveillance, Epidemiology, and End Results database (1973–2010) was reviewed for patients with 1 of the 25 primary cancers. Standardized incidence ratios (SIRs) were calculated as an approximation of relative risk for subsequent CCAs after primary malignancy. Data were stratified by age at primary cancer diagnosis, latency period, and application of radiation.\nA total of 1487 patients developed subsequent CCAs. For patients diagnosed with primary cancers between the ages 20 and 39 years, the risk was increased among colon (SIR 14.65), gallbladder (129.29), and uterus (7.29) cancer survivors. At ages of 40 to 59 years, oral cavity and pharynx (1.89), stomach (3.24), colon (1.76), gallbladder (11.78), and lung cancers (1.75) were associated with increased risk. We found persistently elevated SIRs after colon and gallbladder cancer between ages 60 and 79 years. The SIR remained significant among gallbladder cancer survivors diagnosed after 80 years. Gallbladder cancer showed elevated risk at all of the latency periods except first 6 to 11 months. Increased risk of lung cancer (1.66) was detected after 120 months. However, radiation therapy did not contribute to increased risk.\nThis population-based study suggests that several initial cancers are associated with elevated risk of CCA. The increased risk may be due to shared genetic or environmental etiological factors between these malignancies. Lower threshold for CCA surveillance may be warranted in high-risk patients.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidence Of Subsequent Cholangiocarcinomas After Another Malignancy Cholangiocarcinoma (CCA) characterized by late diagnosis and poor outcomes represents the commonest malignancy of biliary tract. Understanding metachronous cancer associations may achieve earlier detection. We aimed to evaluate the risk of subsequent CCAs among common cancer survivors.\nThe National Cancer Institute's Surveillance, Epidemiology, and End Results database (1973–2010) was reviewed for patients with 1 of the 25 primary cancers. Standardized incidence ratios (SIRs) were calculated as an approximation of relative risk for subsequent CCAs after primary malignancy. Data were stratified by age at primary cancer diagnosis, latency period, and application of radiation.\nA total of 1487 patients developed subsequent CCAs. For patients diagnosed with primary cancers between the ages 20 and 39 years, the risk was increased among colon (SIR 14.65), gallbladder (129.29), and uterus (7.29) cancer survivors. At ages of 40 to 59 years, oral cavity and pharynx (1.89), stomach (3.24), colon (1.76), gallbladder (11.78), and lung cancers (1.75) were associated with increased risk. We found persistently elevated SIRs after colon and gallbladder cancer between ages 60 and 79 years. The SIR remained significant among gallbladder cancer survivors diagnosed after 80 years. Gallbladder cancer showed elevated risk at all of the latency periods except first 6 to 11 months. Increased risk of lung cancer (1.66) was detected after 120 months. However, radiation therapy did not contribute to increased risk.\nThis population-based study suggests that several initial cancers are associated with elevated risk of CCA. The increased risk may be due to shared genetic or environmental etiological factors between these malignancies. Lower threshold for CCA surveillance may be warranted in high-risk patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"surgical outcome biliary tract cancer single institution experience introduction biliary tract cancer rare entity prognosis varies depending location tumor surgical resection remains potentially curative treatment aim study review surgical experience biliary tract cancer patients methods 1992 2010 352 patients biliary tract cancer underwent surgical resection department gastroenterological surgery yokohama city university hospital retrospectively reviewed site cancer hilar bile duct 86 patients distal bile duct 99 patients gallbladder 92 patients papilla vater 75 patients hepatectomy performed 119 patients pancreaticoduodenectomy performed 163 patients local resection bile duct resection cholecystectomy performed 70 patients results morbidity mortality rates 48 8 3 1 respectively curative resection achieved 295 patients 83 8 overall 5 year survival rate patients 48 5 5 year survival rate 97 1 fstage patients 77 5 fstage ii patients 44 8 fstage iii patients 21 3 fstage iva patients 10 1 fstage ivb patients 5 year survival rate 37 5 hilar bile duct cancer 40 0 distal bile duct cancer 50 3 gallbladder cancer 66 9 cancer papilla vater operative culpability hospital death 5year survival rates improved signi cantly period 1992 2001 2002 2010 75 4 4 9 42 2 91 0 1 5 54 3 respectively conclusions surgical outcome biliary tract cancer still poor improved year year improved surgical techniques new chemotherapeutic agents 3d ct technology development surgical devices google scholar","probabilities":0.9799733,"Title":"Surgical Outcome Of Biliary Tract Cancer: Single Institution Experience","Abstract":"Introduction: Biliary tract cancer is a rare entity and its prognosis varies depending on location of tumor. Surgical resection remains the only potentially curative treatment. Aim of this study is to review our surgical experience with biliary tract cancer. Patients and Methods: Between 1992 and 2010, 352 patients with biliary tract cancer who underwent surgical resection at Department of Gastroenterological Surgery, Yokohama City University Hospital, were retrospectively reviewed. Site of cancer was the hilar bile duct in 86 patients, the distal bile duct in 99 patients, the gallbladder in 92 patients, and the papilla of Vater in 75 patients. Hepatectomy was performed in 119 patients, and Pancreaticoduodenectomy was performed in 163 patients. Local resection such as bile duct resection and cholecystectomy was performed in 70 patients. Results: Morbidity and mortality rates were 48.8 and 3.1%, respectively. Curative resection was achieved in 295 patients (83.8%). The overall 5-year survival rate of all patients was 48.5%. The 5-year survival rate was 97.1% for fStage I patients, 77.5% for fStage II patients, 44.8% for fStage III patients, 21.3% for fStage IVa patients and 10.1% for fStage IVb patients. The 5-year survival rate was 37.5% for hilar bile duct cancer, 40.0% for distal bile duct cancer, 50.3% for gallbladder cancer, and 66.9% for cancer of the papilla of Vater. Operative culpability, hospital death and 5year survival rates were improved significantly during the period from 1992 to 2001 and from 2002 to 2010 from 75.4%, 4.9%, 42.2% to 91.0%, 1.5%, and 54.3%, respectively. Conclusions: Surgical outcome of biliary tract cancer is still poor but have been improved year by year with improved surgical techniques, new chemotherapeutic agents, 3D-CT technology and development of surgical devices.","Source":"Google Scholar","category":"HUMAN","training_data":"Surgical Outcome Of Biliary Tract Cancer: Single Institution Experience Introduction: Biliary tract cancer is a rare entity and its prognosis varies depending on location of tumor. Surgical resection remains the only potentially curative treatment. Aim of this study is to review our surgical experience with biliary tract cancer. Patients and Methods: Between 1992 and 2010, 352 patients with biliary tract cancer who underwent surgical resection at Department of Gastroenterological Surgery, Yokohama City University Hospital, were retrospectively reviewed. Site of cancer was the hilar bile duct in 86 patients, the distal bile duct in 99 patients, the gallbladder in 92 patients, and the papilla of Vater in 75 patients. Hepatectomy was performed in 119 patients, and Pancreaticoduodenectomy was performed in 163 patients. Local resection such as bile duct resection and cholecystectomy was performed in 70 patients. Results: Morbidity and mortality rates were 48.8 and 3.1%, respectively. Curative resection was achieved in 295 patients (83.8%). The overall 5-year survival rate of all patients was 48.5%. The 5-year survival rate was 97.1% for fStage I patients, 77.5% for fStage II patients, 44.8% for fStage III patients, 21.3% for fStage IVa patients and 10.1% for fStage IVb patients. The 5-year survival rate was 37.5% for hilar bile duct cancer, 40.0% for distal bile duct cancer, 50.3% for gallbladder cancer, and 66.9% for cancer of the papilla of Vater. Operative culpability, hospital death and 5year survival rates were improved significantly during the period from 1992 to 2001 and from 2002 to 2010 from 75.4%, 4.9%, 42.2% to 91.0%, 1.5%, and 54.3%, respectively. Conclusions: Surgical outcome of biliary tract cancer is still poor but have been improved year by year with improved surgical techniques, new chemotherapeutic agents, 3D-CT technology and development of surgical devices. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"differential requirement de novo lipogenesis cholangiocarcinoma hepatocellular carcinoma mice humans hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc prevalent types primary liver cancer malignancies limited treatment options resulting poor patient outcomes metabolism reprogramming including increased de novo lipogenesis one hallmarks cancer fatty acid synthase fasn catalyzes de novo synthesis long chain fatty acids acetyl coenzyme malonyl coenzyme increased fasn expression reported multiple tumor types inhibition fasn expression shown tumor suppressing activity intriguingly found fasn regulated human hcc samples expression frequently low human icc specimens similar results observed mouse icc models induced different oncogenes ablating fasn mouse liver affect activated akt notch akt notch intracellular domain 1 induced icc formation vivo furthermore hcc icc lesions develop mice following hydrodynamic injection akt neuroblastoma ras viral oncogene homolog oncogenes akt ras deletion fasn akt ras mice triggered development almost exclusively iccs absence fasn icc cells might receive lipids membrane synthesis exogenous fatty acid uptake accordance latter hypothesis icc cells displayed high expression fatty acid uptake related proteins robust long chain fatty acid uptake conclusion data demonstrate fasn dependence universal feature liver tumors hcc development highly dependent fasn mediated lipogenesis icc tumorigenesis insensitive fasn deprivation study supports novel therapeutic approaches treat pernicious tumor type inhibition exogenous fatty acid uptake hepatology 2016 63 1900 1913 stn","probabilities":1.0,"Title":"Differential Requirement For De Novo Lipogenesis In Cholangiocarcinoma And Hepatocellular Carcinoma Of Mice And Humans","Abstract":"Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most prevalent types of primary liver cancer. These malignancies have limited treatment options, resulting in poor patient outcomes. Metabolism reprogramming, including increased de novo lipogenesis, is one of the hallmarks of cancer. Fatty acid synthase (FASN) catalyzes the de novo synthesis of long-chain fatty acids from acetyl-coenzyme A and malonyl-coenzyme A. Increased FASN expression has been reported in multiple tumor types, and inhibition of FASN expression has been shown to have tumor-suppressing activity. Intriguingly, we found that while FASN is up-regulated in human HCC samples, its expression is frequently low in human ICC specimens. Similar results were observed in mouse ICC models induced by different oncogenes. Ablating FASN in the mouse liver did not affect activated AKT and Notch (AKT/Notch intracellular domain 1) induced ICC formation in vivo. Furthermore, while both HCC and ICC lesions develop in mice following hydrodynamic injection of AKT and neuroblastoma Ras viral oncogene homolog oncogenes (AKT/Ras), deletion of FASN in AKT/Ras mice triggered the development almost exclusively of ICCs. In the absence of FASN, ICC cells might receive lipids for membrane synthesis through exogenous fatty acid uptake. In accordance with the latter hypothesis, ICC cells displayed high expression of fatty acid uptake-related proteins and robust long-chain fatty acid uptake. \r\n\r\n Conclusion: Our data demonstrate that FASN dependence is not a universal feature of liver tumors: while HCC development is highly dependent of FASN and its mediated lipogenesis, ICC tumorigenesis can be insensitive to FASN deprivation; our study supports novel therapeutic approaches to treat this pernicious tumor type with the inhibition of exogenous fatty acid uptake. (Hepatology 2016;63:1900-1913).","Source":"STN","category":"ANIMAL","training_data":"Differential Requirement For De Novo Lipogenesis In Cholangiocarcinoma And Hepatocellular Carcinoma Of Mice And Humans Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the most prevalent types of primary liver cancer. These malignancies have limited treatment options, resulting in poor patient outcomes. Metabolism reprogramming, including increased de novo lipogenesis, is one of the hallmarks of cancer. Fatty acid synthase (FASN) catalyzes the de novo synthesis of long-chain fatty acids from acetyl-coenzyme A and malonyl-coenzyme A. Increased FASN expression has been reported in multiple tumor types, and inhibition of FASN expression has been shown to have tumor-suppressing activity. Intriguingly, we found that while FASN is up-regulated in human HCC samples, its expression is frequently low in human ICC specimens. Similar results were observed in mouse ICC models induced by different oncogenes. Ablating FASN in the mouse liver did not affect activated AKT and Notch (AKT/Notch intracellular domain 1) induced ICC formation in vivo. Furthermore, while both HCC and ICC lesions develop in mice following hydrodynamic injection of AKT and neuroblastoma Ras viral oncogene homolog oncogenes (AKT/Ras), deletion of FASN in AKT/Ras mice triggered the development almost exclusively of ICCs. In the absence of FASN, ICC cells might receive lipids for membrane synthesis through exogenous fatty acid uptake. In accordance with the latter hypothesis, ICC cells displayed high expression of fatty acid uptake-related proteins and robust long-chain fatty acid uptake. \r\n\r\n Conclusion: Our data demonstrate that FASN dependence is not a universal feature of liver tumors: while HCC development is highly dependent of FASN and its mediated lipogenesis, ICC tumorigenesis can be insensitive to FASN deprivation; our study supports novel therapeutic approaches to treat this pernicious tumor type with the inhibition of exogenous fatty acid uptake. (Hepatology 2016;63:1900-1913). STN","prediction_labels":"ANIMAL"},{"cleaned":"guided chemotherapy based patient derived mini xenograft models improves survival gallbladder carcinoma patients background gallbladder carcinoma highly aggressive resistant chemotherapy consistent strategy guide first line chemotherapy however patient derived xenograft pdx model increasingly used effective model preclinical study chemosensitivity methods mini pdx model established using freshly resected primary lesions 12 patients gallbladder examine sensitivity five commonly used chemotherapeutic agents namely gemcitabine oxaliplatin 5 fluorouracil nanoparticle albumin bound nab paclitaxel irinotecan results used guide selection chemotherapeutic agents adjunctive treatment surgery kaplan meier method used compare overall survival os disease free survival dfs 45 patients received conventional chemotherapy gemcitabine oxaliplatin results cell viability assays based mini pdx model revealed significant heterogeneities drug responsiveness kaplan meier analysis showed patients pdx guided chemotherapy group significantly longer median os 18 6 months 95 ci 15 9 21 3 months patients conventional chemotherapy group 13 9 months 95 ci 11 7 16 2 months p 0 030 hr 3 18 95 ci 1 47 6 91 patients pdx guided chemotherapy group also significantly longer median dfs 17 6 months 95 ci 14 5 20 6 months patients conventional chemotherapy group 12 0 months 95 ci 9 7 14 4 months p 0 014 hr 3 37 95 ci 1 67 6 79 conclusion use mini pdx model guide selection chemotherapeutic regimens improve outcome patients gallbladder carcinoma stn","probabilities":0.9467213,"Title":"Guided Chemotherapy Based On Patient-Derived Mini-Xenograft Models Improves Survival Of Gallbladder Carcinoma Patients","Abstract":"Background: Gallbladder carcinoma is highly aggressive and resistant to chemotherapy, with no consistent strategy to guide first line chemotherapy. However, patient-derived xenograft (PDX) model has been increasingly used as an effective model for in preclinical study of chemosensitivity. \r\n\r\n Methods: Mini-PDX model was established using freshly resected primary lesions from 12 patients with gallbladder to examine the sensitivity with five of the most commonly used chemotherapeutic agents, namely gemcitabine, oxaliplatin, 5-fluorouracil, nanoparticle albumin-bound (nab)-paclitaxel, and irinotecan. The results were used to guide the selection of chemotherapeutic agents for adjunctive treatment after the surgery. Kaplan-Meier method was used to compare overall survival (OS) and disease free survival (DFS) with 45 patients who received conventional chemotherapy with gemcitabine and oxaliplatin. \r\n\r\n Results: Cell viability assays based on mini-PDX model revealed significant heterogeneities in drug responsiveness. Kaplan-Meier analysis showed that patients in the PDX-guided chemotherapy group had significantly longer median OS (18.6 months; 95% CI 15.9-21.3 months) than patients in the conventional chemotherapy group (13.9 months; 95% CI 11.7-16.2 months) (P = 0.030; HR 3.18; 95% CI 1.47-6.91). Patients in the PDX-guided chemotherapy group also had significantly longer median DFS (17.6 months; 95% CI 14.5-20.6 months) than patients in the conventional chemotherapy group (12.0 months; 95% CI 9.7-14.4 months) (P = 0.014; HR 3.37; 95% CI 1.67-6.79). \r\n\r\n Conclusion: The use of mini-PDX model to guide selection of chemotherapeutic regimens could improve the outcome in patients with gallbladder carcinoma.","Source":"STN","category":"ANIMAL","training_data":"Guided Chemotherapy Based On Patient-Derived Mini-Xenograft Models Improves Survival Of Gallbladder Carcinoma Patients Background: Gallbladder carcinoma is highly aggressive and resistant to chemotherapy, with no consistent strategy to guide first line chemotherapy. However, patient-derived xenograft (PDX) model has been increasingly used as an effective model for in preclinical study of chemosensitivity. \r\n\r\n Methods: Mini-PDX model was established using freshly resected primary lesions from 12 patients with gallbladder to examine the sensitivity with five of the most commonly used chemotherapeutic agents, namely gemcitabine, oxaliplatin, 5-fluorouracil, nanoparticle albumin-bound (nab)-paclitaxel, and irinotecan. The results were used to guide the selection of chemotherapeutic agents for adjunctive treatment after the surgery. Kaplan-Meier method was used to compare overall survival (OS) and disease free survival (DFS) with 45 patients who received conventional chemotherapy with gemcitabine and oxaliplatin. \r\n\r\n Results: Cell viability assays based on mini-PDX model revealed significant heterogeneities in drug responsiveness. Kaplan-Meier analysis showed that patients in the PDX-guided chemotherapy group had significantly longer median OS (18.6 months; 95% CI 15.9-21.3 months) than patients in the conventional chemotherapy group (13.9 months; 95% CI 11.7-16.2 months) (P = 0.030; HR 3.18; 95% CI 1.47-6.91). Patients in the PDX-guided chemotherapy group also had significantly longer median DFS (17.6 months; 95% CI 14.5-20.6 months) than patients in the conventional chemotherapy group (12.0 months; 95% CI 9.7-14.4 months) (P = 0.014; HR 3.37; 95% CI 1.67-6.79). \r\n\r\n Conclusion: The use of mini-PDX model to guide selection of chemotherapeutic regimens could improve the outcome in patients with gallbladder carcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"radiomics approach predict lymph node metastasis clinical outcome intrahepatic cholangiocarcinoma objectives study conducted order establish validate radiomics model predicting lymph node ln metastasis intrahepatic cholangiocarcinoma ihc determine prognostic value methods retrospective study radiomics model developed primary cohort 103 ihc patients underwent curative intent resection lymphadenectomy radiomics features extracted arterial phase computed tomography ct scans radiomics signature built based highly reproducible features using least absolute shrinkage selection operator lasso method multivariate logistic regression analysis adopted establish radiomics model incorporating radiomics signature independent predictors model performance determined discrimination calibration clinical usefulness model internally validated 52 consecutive patients results radiomics signature comprised eight ln status related features showed significant association ln metastasis cohorts p 0 001 radiomics nomogram incorporates radiomics signature ca 19 9 level showed good calibration discrimination primary cohort auc 0 8462 validation cohort auc 0 8921 promisingly radiomics nomogram yielded auc 0 9224 ct reported ln negative subgroup decision curve analysis confirmed clinical utility nomogram high risk metastasis portended significantly lower overall recurrence free survival low risk metastasis p 0 001 radiomics nomogram independent preoperative predictor overall recurrence free survival conclusions radiomics model provided robust diagnostic tool prediction ln metastasis especially ct reported ln negative ihc patients may facilitate clinical decision making key points radiomics nomogram showed good performance prediction ln metastasis ihc patients particularly ct reported ln negative subgroup prognosis high risk patients remains dismal curative intent resection radiomics model may facilitate clinical decision making define patient subsets benefiting surgery pubmed","probabilities":0.9799733,"Title":"A radiomics approach to predict lymph node metastasis and clinical outcome of intrahepatic cholangiocarcinoma","Abstract":"OBJECTIVES: This study was conducted in order to establish and validate a radiomics model for predicting lymph node (LN) metastasis of intrahepatic cholangiocarcinoma (IHC) and to determine its prognostic value. METHODS: For this retrospective study, a radiomics model was developed in a primary cohort of 103 IHC patients who underwent curative-intent resection and lymphadenectomy. Radiomics features were extracted from arterial phase computed tomography (CT) scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients. RESULTS: The radiomics signature comprised eight LN-status-related features and showed significant association with LN metastasis in both cohorts (p < 0.001). A radiomics nomogram that incorporates radiomics signature and CA 19-9 level showed good calibration and discrimination in the primary cohort (AUC 0.8462) and validation cohort (AUC 0.8921). Promisingly, the radiomics nomogram yielded an AUC of 0.9224 in the CT-reported LN-negative subgroup. Decision curve analysis confirmed the clinical utility of this nomogram. High risk for metastasis portended significantly lower overall and recurrence-free survival than low risk for metastasis (both p < 0.001). The radiomics nomogram was an independent preoperative predictor of overall and recurrence-free survival. CONCLUSIONS: Our radiomics model provided a robust diagnostic tool for prediction of LN metastasis, especially in CT-reported LN-negative IHC patients, that may facilitate clinical decision-making. KEY POINTS: • The radiomics nomogram showed good performance for prediction of LN metastasis in IHC patients, particularly in the CT-reported LN-negative subgroup. • Prognosis of high-risk patients remains dismal after curative-intent resection. • The radiomics model may facilitate clinical decision-making and define patient subsets benefiting most from surgery.","Source":"PubMed","category":"HUMAN","training_data":"A radiomics approach to predict lymph node metastasis and clinical outcome of intrahepatic cholangiocarcinoma OBJECTIVES: This study was conducted in order to establish and validate a radiomics model for predicting lymph node (LN) metastasis of intrahepatic cholangiocarcinoma (IHC) and to determine its prognostic value. METHODS: For this retrospective study, a radiomics model was developed in a primary cohort of 103 IHC patients who underwent curative-intent resection and lymphadenectomy. Radiomics features were extracted from arterial phase computed tomography (CT) scans. A radiomics signature was built based on highly reproducible features using the least absolute shrinkage and selection operator (LASSO) method. Multivariate logistic regression analysis was adopted to establish a radiomics model incorporating radiomics signature and other independent predictors. Model performance was determined by its discrimination, calibration, and clinical usefulness. The model was internally validated in 52 consecutive patients. RESULTS: The radiomics signature comprised eight LN-status-related features and showed significant association with LN metastasis in both cohorts (p < 0.001). A radiomics nomogram that incorporates radiomics signature and CA 19-9 level showed good calibration and discrimination in the primary cohort (AUC 0.8462) and validation cohort (AUC 0.8921). Promisingly, the radiomics nomogram yielded an AUC of 0.9224 in the CT-reported LN-negative subgroup. Decision curve analysis confirmed the clinical utility of this nomogram. High risk for metastasis portended significantly lower overall and recurrence-free survival than low risk for metastasis (both p < 0.001). The radiomics nomogram was an independent preoperative predictor of overall and recurrence-free survival. CONCLUSIONS: Our radiomics model provided a robust diagnostic tool for prediction of LN metastasis, especially in CT-reported LN-negative IHC patients, that may facilitate clinical decision-making. KEY POINTS: • The radiomics nomogram showed good performance for prediction of LN metastasis in IHC patients, particularly in the CT-reported LN-negative subgroup. • Prognosis of high-risk patients remains dismal after curative-intent resection. • The radiomics model may facilitate clinical decision-making and define patient subsets benefiting most from surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"development prognostic model predicts survival pancreaticoduodenectomy ampullary cancer objectives aims study identify independent predictors survival pancreaticoduodenectomy ampullary cancer ii develop prognostic model survival methods data analyzed retrospectively 110 consecutive patients underwent pancreaticoduodenectomy 2002 2013 subjects categorized 3 nodal subgroups per recently proposed nodal subclassification n0 node negative n1 1 2 metastatic nodes n2 3 metastatic nodes clinicopathological features overall survival compared kaplan meier cox regression analyses results overall 1 3 5 year survival rates 79 8 42 2 34 9 respectively overall 1 3 5 year survival rates n0 group 85 2 71 9 67 4 respectively 1 3 5 year survival rates n1 n2 subgroups 81 5 49 4 49 4 75 19 2 6 4 respectively log rank p 0 0001 performing multivariate cox regression analysis vascular invasion lymph node ratio independent predictors survival hence prediction model survival constructed based 2 variables conclusions using data carefully selected cohort patients created pilot prognostic model postresectional survival proposed model may help clinicians guide treatments adjuvant setting pubmed","probabilities":0.9799733,"Title":"Development of a Prognostic Model That Predicts Survival After Pancreaticoduodenectomy for Ampullary Cancer","Abstract":"OBJECTIVES: The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival. METHODS: Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1-2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses. RESULTS: The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables. CONCLUSIONS: Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting.","Source":"PubMed","category":"HUMAN","training_data":"Development of a Prognostic Model That Predicts Survival After Pancreaticoduodenectomy for Ampullary Cancer OBJECTIVES: The aims of this study were to (i) identify independent predictors of survival after pancreaticoduodenectomy for ampullary cancer and (ii) develop a prognostic model of survival. METHODS: Data were analyzed retrospectively on 110 consecutive patients who underwent pancreaticoduodenectomy between 2002 and 2013. Subjects were categorized into 3 nodal subgroups as per the recently proposed nodal subclassification: N0 (node negative), N1 (1-2 metastatic nodes), or N2 (≥3 metastatic nodes). Clinicopathological features and overall survival were compared by Kaplan-Meier and Cox regression analyses. RESULTS: The overall 1-, 3-, and 5-year survival rates were 79.8%, 42.2%, and 34.9%, respectively. The overall 1-, 3-, and 5-year survival rates for the N0 group were 85.2%, 71.9%, and 67.4%, respectively. The 1-, 3-, 5-year survival rates for the N1 and N2 subgroups were 81.5%, 49.4%, and 49.4% and 75%, 19.2%, and 6.4%, respectively (log rank, P < 0.0001). After performing a multivariate Cox regression analysis, vascular invasion and lymph node ratio were the only independent predictors of survival. Hence, a prediction model of survival was constructed based on those 2 variables. CONCLUSIONS: Using data from a carefully selected cohort of patients, we created a pilot prognostic model of postresectional survival. The proposed model may help clinicians to guide treatments in the adjuvant setting. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors bile duct cancers patients receiving pretreatment fdg pet ct abstract avilable google scholar","probabilities":0.9799733,"Title":"Prognostic Factors Of Bile Duct Cancers In Patients Receiving Pretreatment Fdg Pet/Ct","Abstract":"Abstract not avilable","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Factors Of Bile Duct Cancers In Patients Receiving Pretreatment Fdg Pet/Ct Abstract not avilable Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"incidental pt2 t3 gallbladder cancer cholecystectomy outcome staging 3 months prior radical resection introduction patients incidental pt2 t3 gallbladder cancer igc cholecystectomy may benefit radical re resection although optimal treatment strategy well defined unit patients undergo delayed staging 3 months cholecystectomy assess evidence residual tumour extra hepatic spread biological behaviour tumour aim study evaluate outcome patients delayed staging 3 months cholecystectomy methods july 2003 july 2011 56 patients t2 t3 gallbladder cancer referred unit 49 diagnosed incidentally histology cholecystectomy 49 patients underwent delayed pre operative staging using multi detector computed tomography mdct followed selectively laparoscopy 3 months cholecystectomy data collected prospectively held database peri operative long term outcomes patients analysed spss software used statistical analysis results 38 pt2 11 pt3 tumours delayed staging 24 49 49 patients underwent radical resection 24 49 49 found inoperable pre operative assessment 1 49 2 patient underwent exploratory laparotomy found unresectable overall median survival referral 20 7 months 54 8 months group radical re resection versus 9 7 months group unresectable disease p 0 001 results compare favourably reported outcome fast track management incidental pt2 t3 gallbladder cancer major series literature conclusion delayed staging patients incidental t2 t3 gallbladder cancer cholecystectomy useful strategy select patients benefit resection avoid unnecessary major surgery pubmed","probabilities":0.9799733,"Title":"Incidental pT2-T3 gallbladder cancer after a cholecystectomy: outcome of staging at 3 months prior to a radical resection","Abstract":"INTRODUCTION: Patients with incidental pT2-T3 gallbladder cancer (IGC) after a cholecystectomy may benefit from a radical re-resection although their optimal treatment strategy is not well defined. In this Unit, such patients undergo delayed staging at 3 months after a cholecystectomy to assess the evidence of a residual tumour, extra hepatic spread and the biological behaviour of the tumour. The aim of this study was to evaluate the outcome of patients who had delayed staging at 3 months after a cholecystectomy. METHODS: From July 2003 to July 2011, 56 patients with T2-T3 gallbladder cancer were referred to this Unit of which 49 were diagnosed incidentally on histology after a cholecystectomy. All 49 patients underwent delayed pre-operative staging using multi-detector computed tomography (MDCT) followed selectively by laparoscopy at 3 months after a cholecystectomy. Data were collected from a prospectively held database. The peri-operative and long-term outcomes of patients were analysed. SPSS software was used for statistical analysis. RESULTS: There were 38 pT2 and 11 pT3 tumours. After delayed staging, 24/49 (49%) patients underwent a radical resection, 24/49 (49%) were found to be inoperable on pre-operative assessment and 1/49 (2%) patient underwent an exploratory laparotomy and were found to be unresectable. The overall median survival from referral was 20.7 months (54.8 months for the group who had a radical re-resection versus 9.7 months for the group who had unresectable disease, P < 0.001). These results compare favourably with the reported outcome of fast-track management for incidental pT2-T3 gallbladder cancer from other major series in the literature. CONCLUSION: Delayed staging in patients with incidental T2-T3 gallbladder cancer after a cholecystectomy is a useful strategy to select patients who will benefit from a resection and avoid unnecessary major surgery.","Source":"PubMed","category":"HUMAN","training_data":"Incidental pT2-T3 gallbladder cancer after a cholecystectomy: outcome of staging at 3 months prior to a radical resection INTRODUCTION: Patients with incidental pT2-T3 gallbladder cancer (IGC) after a cholecystectomy may benefit from a radical re-resection although their optimal treatment strategy is not well defined. In this Unit, such patients undergo delayed staging at 3 months after a cholecystectomy to assess the evidence of a residual tumour, extra hepatic spread and the biological behaviour of the tumour. The aim of this study was to evaluate the outcome of patients who had delayed staging at 3 months after a cholecystectomy. METHODS: From July 2003 to July 2011, 56 patients with T2-T3 gallbladder cancer were referred to this Unit of which 49 were diagnosed incidentally on histology after a cholecystectomy. All 49 patients underwent delayed pre-operative staging using multi-detector computed tomography (MDCT) followed selectively by laparoscopy at 3 months after a cholecystectomy. Data were collected from a prospectively held database. The peri-operative and long-term outcomes of patients were analysed. SPSS software was used for statistical analysis. RESULTS: There were 38 pT2 and 11 pT3 tumours. After delayed staging, 24/49 (49%) patients underwent a radical resection, 24/49 (49%) were found to be inoperable on pre-operative assessment and 1/49 (2%) patient underwent an exploratory laparotomy and were found to be unresectable. The overall median survival from referral was 20.7 months (54.8 months for the group who had a radical re-resection versus 9.7 months for the group who had unresectable disease, P < 0.001). These results compare favourably with the reported outcome of fast-track management for incidental pT2-T3 gallbladder cancer from other major series in the literature. CONCLUSION: Delayed staging in patients with incidental T2-T3 gallbladder cancer after a cholecystectomy is a useful strategy to select patients who will benefit from a resection and avoid unnecessary major surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"update hepatocellular carcinoma pathologists review histopathologic diversity several distinct histologic subtypes hepatocellular carcinoma hcc well recognized recent advances molecular pathology growing knowledge biology associated distinct histologic features immuno profile hcc allowed pathologists update classifications improving sub classification allow clinically relevant diagnoses may allow stratification biologically meaningful subgroups therefore immuno histochemical molecular testing diagnostically useful also incorporated crucial components predicting prognosis patients hcc possibilities targeted therapy explored hcc important pathologists provide data may valuable theranostic perspective herein review provide updates regarding pathologic sub classification hcc pathologic diagnostic approach role biomarkers prognosticators reviewed histopathology four particular subtypes hcc steatohepatitic clear cell fibrolamellar scirrhous clinical relevance recent consensus combined hcc cholangiocarcinoma summarized finally emerging novel biomarkers new approaches hcc stratification reviewed pubmed","probabilities":0.962963,"Title":"Update on hepatocellular carcinoma: Pathologists' review","Abstract":"Histopathologic diversity and several distinct histologic subtypes of hepatocellular carcinoma (HCC) are well-recognized. Recent advances in molecular pathology and growing knowledge about the biology associated with distinct histologic features and immuno-profile in HCC allowed pathologists to update classifications. Improving sub-classification will allow for more clinically relevant diagnoses and may allow for stratification into biologically meaningful subgroups. Therefore, immuno-histochemical and molecular testing are not only diagnostically useful, but also are being incorporated as crucial components in predicting prognosis of the patients with HCC. Possibilities of targeted therapy are being explored in HCC, and it will be important for pathologists to provide any data that may be valuable from a theranostic perspective. Herein, we review and provide updates regarding the pathologic sub-classification of HCC. Pathologic diagnostic approach and the role of biomarkers as prognosticators are reviewed. Further, the histopathology of four particular subtypes of HCC: Steatohepatitic, clear cell, fibrolamellar and scirrhous - and their clinical relevance, and the recent consensus on combined HCC-cholangiocarcinoma is summarized. Finally, emerging novel biomarkers and new approaches to HCC stratification are reviewed.","Source":"PubMed","category":"HUMAN","training_data":"Update on hepatocellular carcinoma: Pathologists' review Histopathologic diversity and several distinct histologic subtypes of hepatocellular carcinoma (HCC) are well-recognized. Recent advances in molecular pathology and growing knowledge about the biology associated with distinct histologic features and immuno-profile in HCC allowed pathologists to update classifications. Improving sub-classification will allow for more clinically relevant diagnoses and may allow for stratification into biologically meaningful subgroups. Therefore, immuno-histochemical and molecular testing are not only diagnostically useful, but also are being incorporated as crucial components in predicting prognosis of the patients with HCC. Possibilities of targeted therapy are being explored in HCC, and it will be important for pathologists to provide any data that may be valuable from a theranostic perspective. Herein, we review and provide updates regarding the pathologic sub-classification of HCC. Pathologic diagnostic approach and the role of biomarkers as prognosticators are reviewed. Further, the histopathology of four particular subtypes of HCC: Steatohepatitic, clear cell, fibrolamellar and scirrhous - and their clinical relevance, and the recent consensus on combined HCC-cholangiocarcinoma is summarized. Finally, emerging novel biomarkers and new approaches to HCC stratification are reviewed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"increased chromosome 7 copy number endoscopic bile duct biopsy specimens predictive poor prognosis cholangiocarcinoma background ability fluorescence situ hybridization fish assays endoscopic transpapillary bile duct biopsy specimens predict prognosis cholangiocarcinoma cca elucidated aims aimed clarify association results urovysion fish assays prognosis cca methods retrospectively reviewed 49 specimens obtained transpapillary forceps biopsy consecutive patients cca copy numbers chromosomes 3 7 17 evaluated fish assay using urovysion compared overall survival os cca patients without increased copy numbers chromosomes 3 7 17 furthermore evaluated association os clinicopathological parameters cca patients results os significantly shorter patients without increased chromosome 7 copy number log rank p 0 015 median os 11 9 vs 20 7 months univariate analyses age p 0 012 ecog performance status p 0 046 tumor stage p 0 046 surgery p 0 006 increased chromosome 7 copy number p 0 017 significantly associated os multivariate analysis revealed increased chromosome 7 copy number hazard ratio 2 46 95 ci 1 15 5 27 p 0 021 advanced clinical stage hazard ratio 2 26 95 ci 1 11 4 63 p 0 025 independently predictive poor os conclusions detection fish assay increased chromosome 7 copy number transpapillary forceps biopsy specimens predictive poor prognosis cca patients pubmed","probabilities":0.5555556,"Title":"An Increased Chromosome 7 Copy Number in Endoscopic Bile Duct Biopsy Specimens Is Predictive of a Poor Prognosis in Cholangiocarcinoma","Abstract":"BACKGROUND: The ability of fluorescence in situ hybridization (FISH) assays in endoscopic transpapillary bile duct biopsy specimens to predict the prognosis of cholangiocarcinoma (CCA) has not been elucidated. AIMS: We aimed to clarify the association between the results of UroVysion FISH assays and the prognosis of CCA. METHODS: We retrospectively reviewed 49 specimens obtained by transpapillary forceps biopsy from consecutive patients with CCA. The copy numbers of chromosomes 3, 7, and 17 were evaluated by FISH assay using UroVysion. We compared the overall survival (OS) of CCA patients with and without increased copy numbers of chromosomes 3, 7, and 17. Furthermore, we evaluated the association between OS and the clinicopathological parameters of CCA patients. RESULTS: The OS was significantly shorter in patients with than without an increased chromosome 7 copy number (log-rank p = 0.015; median OS 11.9 vs. 20.7 months). In the univariate analyses, age (p = 0.012), ECOG performance status (p = 0.046), tumor stage (p = 0.046), surgery (p = 0.006), and an increased chromosome 7 copy number (p = 0.017) were significantly associated with OS. The multivariate analysis revealed that an increased chromosome 7 copy number (hazard ratio, 2.46; 95% CI 1.15-5.27; p = 0.021) and advanced clinical stage (hazard ratio, 2.26; 95% CI 1.11-4.63; p = 0.025) were independently predictive of a poor OS. CONCLUSIONS: Detection by FISH assay of an increased chromosome 7 copy number in transpapillary forceps biopsy specimens is predictive of a poor prognosis in CCA patients.","Source":"PubMed","category":"ANIMAL","training_data":"An Increased Chromosome 7 Copy Number in Endoscopic Bile Duct Biopsy Specimens Is Predictive of a Poor Prognosis in Cholangiocarcinoma BACKGROUND: The ability of fluorescence in situ hybridization (FISH) assays in endoscopic transpapillary bile duct biopsy specimens to predict the prognosis of cholangiocarcinoma (CCA) has not been elucidated. AIMS: We aimed to clarify the association between the results of UroVysion FISH assays and the prognosis of CCA. METHODS: We retrospectively reviewed 49 specimens obtained by transpapillary forceps biopsy from consecutive patients with CCA. The copy numbers of chromosomes 3, 7, and 17 were evaluated by FISH assay using UroVysion. We compared the overall survival (OS) of CCA patients with and without increased copy numbers of chromosomes 3, 7, and 17. Furthermore, we evaluated the association between OS and the clinicopathological parameters of CCA patients. RESULTS: The OS was significantly shorter in patients with than without an increased chromosome 7 copy number (log-rank p = 0.015; median OS 11.9 vs. 20.7 months). In the univariate analyses, age (p = 0.012), ECOG performance status (p = 0.046), tumor stage (p = 0.046), surgery (p = 0.006), and an increased chromosome 7 copy number (p = 0.017) were significantly associated with OS. The multivariate analysis revealed that an increased chromosome 7 copy number (hazard ratio, 2.46; 95% CI 1.15-5.27; p = 0.021) and advanced clinical stage (hazard ratio, 2.26; 95% CI 1.11-4.63; p = 0.025) were independently predictive of a poor OS. CONCLUSIONS: Detection by FISH assay of an increased chromosome 7 copy number in transpapillary forceps biopsy specimens is predictive of a poor prognosis in CCA patients. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"air cholangiogram new technique biliary imaging ercp background palliation patients malignant hilar stenosis stent insertion fraught risk cholangitis contrast injection undrained segment objective purpose study evaluate results unilateral metal stenting type ii iii malignant hilar biliary obstruction using air contrast medium design prospective uncontrolled single center pilot study setting tertiary care referral center patients cohort 17 patients malignant hilar obstruction intervention single metallic stent inserted type ii iii malignant hilar obstruction using air contrast medium patients evaluated weekly 1 month stent placement main outcome measures successful implantation successful drainage early complications procedure related mortality 30 day mortality result successful stent placement drainage achieved 100 patients 17 17 patient developed cholangitis died within 30 days procedure limitations small cohort patients conclusion air cholangiography provides safe effective roadmap unilateral metallic stenting type ii iii malignant hilar biliary obstruction pubmed","probabilities":0.9799733,"Title":"Air cholangiogram: a new technique for biliary imaging during ERCP","Abstract":"BACKGROUND: Palliation of patients with malignant hilar stenosis by stent insertion is fraught with risk of cholangitis because of contrast injection in the undrained segment. OBJECTIVE: The purpose of this study was to evaluate the results of unilateral metal stenting in type II and III malignant hilar biliary obstruction by using air as a contrast medium. DESIGN: Prospective, uncontrolled, single center pilot study. SETTING: Tertiary care referral center. PATIENTS: Cohort of 17 patients with malignant hilar obstruction. INTERVENTION: A single metallic stent was inserted in type II and III malignant hilar obstruction by using air as a contrast medium. Patients were evaluated weekly up to 1 month after stent placement. MAIN OUTCOME MEASURES: Successful implantation, successful drainage, early complications, procedure-related mortality, 30-day mortality. RESULT: Successful stent placement and drainage was achieved in 100% of the patients (17 of 17). No patient developed cholangitis or died within 30 days of the procedure. LIMITATIONS: Small cohort of patients. CONCLUSION: Air cholangiography provides a safe and effective roadmap for unilateral metallic stenting in type II and III malignant hilar biliary obstruction.","Source":"PubMed","category":"HUMAN","training_data":"Air cholangiogram: a new technique for biliary imaging during ERCP BACKGROUND: Palliation of patients with malignant hilar stenosis by stent insertion is fraught with risk of cholangitis because of contrast injection in the undrained segment. OBJECTIVE: The purpose of this study was to evaluate the results of unilateral metal stenting in type II and III malignant hilar biliary obstruction by using air as a contrast medium. DESIGN: Prospective, uncontrolled, single center pilot study. SETTING: Tertiary care referral center. PATIENTS: Cohort of 17 patients with malignant hilar obstruction. INTERVENTION: A single metallic stent was inserted in type II and III malignant hilar obstruction by using air as a contrast medium. Patients were evaluated weekly up to 1 month after stent placement. MAIN OUTCOME MEASURES: Successful implantation, successful drainage, early complications, procedure-related mortality, 30-day mortality. RESULT: Successful stent placement and drainage was achieved in 100% of the patients (17 of 17). No patient developed cholangitis or died within 30 days of the procedure. LIMITATIONS: Small cohort of patients. CONCLUSION: Air cholangiography provides a safe and effective roadmap for unilateral metallic stenting in type II and III malignant hilar biliary obstruction. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term trends incidence mortality intrahepatic extrahepatic bile duct cancer japan background report multiple cases bile duct cancer japanese printing company raised concern cancers examined long term trends bile duct cancer japan methods data 4 population based cancer registries used calculate incidence 1985 2007 vital statistics used estimate mortality 1985 2011 age standardized rates calculated analyzed using joinpoint regression model results among men incidence rate intrahepatic bile duct cancer increased throughout observation period among women increased 1996 1998 remained stable thereafter incidence rate extrahepatic bile duct cancer stable men decreased 1993 1995 women people aged 30 49 years incidence rates intra extrahepatic bile duct cancer remained stable decreased mortality rate intrahepatic bile duct cancer increased sexes age groups since 1996 extrahepatic bile duct cancer decreased since 1992 people aged 30 49 years mortality rates intra extrahepatic bile duct cancer remained stable decreased respectively conclusions incidence mortality rates intrahepatic bile duct cancer remained stable increased throughout observation period incidence rate extrahepatic bile duct cancer remained stable decreased mortality rate decreased since 1992 people aged 30 49 years incidence mortality rates intra extrahepatic bile cancer remained stable decreased stn","probabilities":0.9799733,"Title":"Long-Term Trends In Incidence And Mortality Of Intrahepatic And Extrahepatic Bile Duct Cancer In Japan","Abstract":"Background: A report of multiple cases of bile duct cancer at a Japanese printing company raised concern about such cancers. We examined long-term trends in bile duct cancer in Japan. \r\n\r\n Methods: Data from 4 population-based cancer registries were used to calculate incidence between 1985 and 2007, and vital statistics were used to estimate mortality between 1985 and 2011. Age-standardized rates were calculated and analyzed using a joinpoint regression model. \r\n\r\n Results: Among men, the incidence rate of intrahepatic bile duct cancer increased throughout the observation period; among women, it increased until 1996-1998 and remained stable thereafter. The incidence rate of extrahepatic bile duct cancer was stable in men and decreased from 1993-1995 in women. In people aged 30 to 49 years, the incidence rates of intra- and extrahepatic bile duct cancer remained stable or decreased. The mortality rate of intrahepatic bile duct cancer increased in both sexes and in all age groups since 1996, while that of extrahepatic bile duct cancer decreased since 1992. In people aged 30 to 49 years, the mortality rates of intra- and extrahepatic bile duct cancer remained stable and decreased, respectively. \r\n\r\n Conclusions: The incidence and mortality rates of intrahepatic bile duct cancer remained stable or increased throughout the observation period. The incidence rate of extrahepatic bile duct cancer remained stable or decreased, and the mortality rate decreased since 1992. In people aged 30 to 49 years, the incidence and mortality rates of intra- and extrahepatic bile cancer remained stable or decreased.","Source":"STN","category":"HUMAN","training_data":"Long-Term Trends In Incidence And Mortality Of Intrahepatic And Extrahepatic Bile Duct Cancer In Japan Background: A report of multiple cases of bile duct cancer at a Japanese printing company raised concern about such cancers. We examined long-term trends in bile duct cancer in Japan. \r\n\r\n Methods: Data from 4 population-based cancer registries were used to calculate incidence between 1985 and 2007, and vital statistics were used to estimate mortality between 1985 and 2011. Age-standardized rates were calculated and analyzed using a joinpoint regression model. \r\n\r\n Results: Among men, the incidence rate of intrahepatic bile duct cancer increased throughout the observation period; among women, it increased until 1996-1998 and remained stable thereafter. The incidence rate of extrahepatic bile duct cancer was stable in men and decreased from 1993-1995 in women. In people aged 30 to 49 years, the incidence rates of intra- and extrahepatic bile duct cancer remained stable or decreased. The mortality rate of intrahepatic bile duct cancer increased in both sexes and in all age groups since 1996, while that of extrahepatic bile duct cancer decreased since 1992. In people aged 30 to 49 years, the mortality rates of intra- and extrahepatic bile duct cancer remained stable and decreased, respectively. \r\n\r\n Conclusions: The incidence and mortality rates of intrahepatic bile duct cancer remained stable or increased throughout the observation period. The incidence rate of extrahepatic bile duct cancer remained stable or decreased, and the mortality rate decreased since 1992. In people aged 30 to 49 years, the incidence and mortality rates of intra- and extrahepatic bile cancer remained stable or decreased. STN","prediction_labels":"HUMAN"},{"cleaned":"ca19 9 kinetics systemic chemotherapy patients advanced recurrent biliary tract cancer purpose role carbohydrate antigen 19 9 ca19 9 kinetics patients biliary tract cancer btc receiving chemotherapy remains elucidated methods total 185 advanced recurrent btc patients receiving first line chemotherapy january 2006 march 2016 retrospectively studied serum ca19 9 measured baseline two cycles chemotherapy patients categorized based ca19 9 response ca19 9 decrease group 30 decrease stable group 30 decrease 20 increase increase group 20 increase associations ca19 9 response radiological tumor response progression free survival pfs overall survival os investigated results statistically significant association ca19 9 response radiological tumor responses p 0 001 median pfs os significantly different among three groups according ca19 9 response pfs 8 0 5 7 3 5 months ca19 9 decrease stable increase groups p 0 001 os 18 8 16 0 7 5 months ca19 9 decrease stable increase groups respectively p 0 001 multivariate analyses showed ca19 9 response prognostic os pfs addition ca19 9 baseline performance status conclusion ca19 9 kinetics first two cycles first line chemotherapy prognostic factor os pfs patients advanced recurrent btc pubmed","probabilities":0.9799733,"Title":"CA19-9 kinetics during systemic chemotherapy in patients with advanced or recurrent biliary tract cancer","Abstract":"PURPOSE: The role of carbohydrate antigen 19-9 (CA19-9) kinetics in patients with biliary tract cancer (BTC) receiving chemotherapy remains to be elucidated. METHODS: A total of 185 advanced or recurrent BTC patients receiving a first line chemotherapy between January 2006 and March 2016, were retrospectively studied. Serum CA19-9 was measured at baseline and after two cycles of chemotherapy, and patients were categorized based on CA19-9 response: CA19-9 decrease group (≥ 30% decrease), stable group (< 30% decrease and < 20% increase) and increase group (≥ 20% increase). The associations of CA19-9 response with radiological tumor response, progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: There was a statistically significant association between CA19-9 response and radiological tumor responses (p < 0.001). The median PFS and OS were significantly different among three groups according to CA19-9 response: PFS of 8.0, 5.7 and 3.5 months in CA19-9 decrease, stable and increase groups (p < 0.001) and OS of 18.8, 16.0 and 7.5 months in CA19-9 decrease, stable and increase groups, respectively (p < 0.001). Multivariate analyses showed that CA19-9 response was prognostic both of OS and PFS in addition, to CA19-9 at baseline, and performance status. CONCLUSION: CA19-9 kinetics after the first two cycles of a first line chemotherapy was a prognostic factor for OS and PFS in patients with advanced and recurrent BTC.","Source":"PubMed","category":"HUMAN","training_data":"CA19-9 kinetics during systemic chemotherapy in patients with advanced or recurrent biliary tract cancer PURPOSE: The role of carbohydrate antigen 19-9 (CA19-9) kinetics in patients with biliary tract cancer (BTC) receiving chemotherapy remains to be elucidated. METHODS: A total of 185 advanced or recurrent BTC patients receiving a first line chemotherapy between January 2006 and March 2016, were retrospectively studied. Serum CA19-9 was measured at baseline and after two cycles of chemotherapy, and patients were categorized based on CA19-9 response: CA19-9 decrease group (≥ 30% decrease), stable group (< 30% decrease and < 20% increase) and increase group (≥ 20% increase). The associations of CA19-9 response with radiological tumor response, progression-free survival (PFS) and overall survival (OS) were investigated. RESULTS: There was a statistically significant association between CA19-9 response and radiological tumor responses (p < 0.001). The median PFS and OS were significantly different among three groups according to CA19-9 response: PFS of 8.0, 5.7 and 3.5 months in CA19-9 decrease, stable and increase groups (p < 0.001) and OS of 18.8, 16.0 and 7.5 months in CA19-9 decrease, stable and increase groups, respectively (p < 0.001). Multivariate analyses showed that CA19-9 response was prognostic both of OS and PFS in addition, to CA19-9 at baseline, and performance status. CONCLUSION: CA19-9 kinetics after the first two cycles of a first line chemotherapy was a prognostic factor for OS and PFS in patients with advanced and recurrent BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tumor marker kinetics prognosticators patients unresectable gallbladder adenocarcinoma undergoing palliative chemotherapy background aims determine prognostic value carcinoembryonic antigen cea carbohydrate antigen ca 19 9 gallbladder cancer gbc palliative chemotherapy methods one hundred twenty three patients pathologically confirmed unresectable gbc included differences serum cea ca 19 9 levels chemotherapy measured receiver operating characteristic curve analysis kaplan meier analyses cea ca 19 9 combined changes performed assess optimal cutoff values survival rates results patients decreased tumor markers significantly better progression free survival pfs overall survival os patients increased tumor markers pre postchemotherapy ca 19 9 ratio highest area curve values predicting 3 month pfs 1 year os multivariate analysis increases serum ca 19 9 palliative chemotherapy patients unresectable gbc independent prognosticator poor pfs os hazard ratios 2 20 p 0 001 1 67 p 0 020 respectively patients increases 10 fold considered progressive disease whereas individuals increases 3 fold likely benefit early imaging follow conclusions ca 19 9 kinetics reliable prognosticator pfs os patients unresectable gbc underwent palliative chemotherapy pubmed","probabilities":0.9799733,"Title":"Tumor Marker Kinetics as Prognosticators in Patients with Unresectable Gallbladder Adenocarcinoma Undergoing Palliative Chemotherapy","Abstract":"BACKGROUND/AIMS: To determine the prognostic value of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during palliative chemotherapy. METHODS: One hundred and twenty-three patients with pathologically confirmed unresectable GBC were included. Differences in serum CEA and CA 19-9 levels before and after chemotherapy were measured. Receiver operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9, and combined changes were performed to assess the optimal cutoff values and survival rates. RESULTS: Patients with decreased tumor markers had significantly better progression-free survival (PFS) and overall survival (OS) than patients with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In the multivariate analysis, increases in serum CA 19-9 during palliative chemotherapy in patients with unresectable GBC was an independent prognosticator of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020), respectively. Patients with increases ＞10-fold were considered to have progressive disease, whereas individuals with increases ＞3-fold were likely to benefit from early imaging follow-up. CONCLUSIONS: CA 19-9 kinetics was a reliable prognosticator of PFS and OS in patients with unresectable GBC who underwent palliative chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"Tumor Marker Kinetics as Prognosticators in Patients with Unresectable Gallbladder Adenocarcinoma Undergoing Palliative Chemotherapy BACKGROUND/AIMS: To determine the prognostic value of carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 in gallbladder cancer (GBC) during palliative chemotherapy. METHODS: One hundred and twenty-three patients with pathologically confirmed unresectable GBC were included. Differences in serum CEA and CA 19-9 levels before and after chemotherapy were measured. Receiver operating characteristic curve analysis, Kaplan-Meier analyses of CEA, CA 19-9, and combined changes were performed to assess the optimal cutoff values and survival rates. RESULTS: Patients with decreased tumor markers had significantly better progression-free survival (PFS) and overall survival (OS) than patients with increased tumor markers. The pre- and postchemotherapy CA 19-9 ratio had the highest area-under-the-curve values for predicting 3-month PFS and 1-year OS. In the multivariate analysis, increases in serum CA 19-9 during palliative chemotherapy in patients with unresectable GBC was an independent prognosticator of poor PFS and OS, with hazard ratios of 2.20 (p=0.001) and 1.67 (p=0.020), respectively. Patients with increases ＞10-fold were considered to have progressive disease, whereas individuals with increases ＞3-fold were likely to benefit from early imaging follow-up. CONCLUSIONS: CA 19-9 kinetics was a reliable prognosticator of PFS and OS in patients with unresectable GBC who underwent palliative chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"trends incidence treatment outcomes patients intrahepatic cholangiocarcinoma usa facility type associated margin status use lymphadenectomy overall survival introduction intrahepatic cholangiocarcinoma icc remains uncommon disease rising incidence worldwide sought identify trends therapeutic approaches differences patient outcomes based facility types methods january 1 2004 december 31 2015 total 27 120 patients histologic diagnosis icc identified national cancer database enrolled study results incidence icc patients increased 1194 2004 3821 2015 average annual increase 4 16 p 0 001 median survival cohort improved last 6 years study period 2004 2009 8 05 months vs 2010 2015 9 49 months p 0 001 among surgical patients n 5943 21 9 incidence r0 resection lymphadenectomy harvest 6 lymph nodes increased time p 0 001 positive surgical margins referent r0 r1 hr 1 49 95 ci 1 24 1 79 p 0 001 treatment community cancer centers referent academic centers hr 1 24 95 ci 1 04 1 49 p 0 023 associated worse prognosis patients treated academic centers higher rates r0 resection 72 4 vs 67 7 p 0 006 lymphadenectomy 55 6 vs 49 5 p 0 009 versus community cancer centers overall survival also better academic versus community cancer programs median os 11 months versus 6 months respectively p 0 001 conclusions incidence icc increased last 12 years usa moderate improvement survival time treatment academic cancer centers associated higher r0 resection lymphadenectomy rates well improved os patients icc stn","probabilities":0.9799733,"Title":"Trends In The Incidence Treatment And Outcomes Of Patients With Intrahepatic Cholangiocarcinoma In The Usa: Facility Type Is Associated With Margin Status Use Of Lymphadenectomy And Overall Survival","Abstract":"Introduction: Intrahepatic cholangiocarcinoma (ICC) remains an uncommon disease with a rising incidence worldwide. We sought to identify trends in therapeutic approaches and differences in patient outcomes based on facility types. \r\n\r\n Methods: Between January 1, 2004, and December 31, 2015, a total of 27,120 patients with histologic diagnosis of ICC were identified in the National Cancer Database and were enrolled in this study. \r\n\r\n Results: The incidence of ICC patients increased from 1194 in 2004 to 3821 in 2015 with an average annual increase of 4.16% (p < 0.001). Median survival of the cohort improved over the last 6 years of the study period (2004-2009: 8.05 months vs. 2010-2015: 9.49 months; p < 0.001). Among surgical patients (n = 5943, 21.9%), the incidence of R0 resection, lymphadenectomy and harvest of ≥6 lymph nodes increased over time (p < 0.001). Positive surgical margins (referent R0: R1, HR 1.49, 95% CI 1.24-1.79, p < 0.001) and treatment at community cancer centers (referent academic centers; HR 1.24, 95% CI 1.04-1.49, p = 0.023) were associated with a worse prognosis. Patients treated at academic centers had higher rates of R0 resection (72.4% vs. 67.7%; p = 0.006) and lymphadenectomy (55.6% vs. 49.5%, p = 0.009) versus community cancer centers. Overall survival was also better at academic versus community cancer programs (median OS: 11 months versus 6 months, respectively; p < 0.001). \r\n\r\n Conclusions: The incidence of ICC has increased over the last 12 years in the USA with a moderate improvement in survival over time. Treatment at academic cancer centers was associated with higher R0 resection and lymphadenectomy rates, as well as improved OS for patients with ICC.","Source":"STN","category":"HUMAN","training_data":"Trends In The Incidence Treatment And Outcomes Of Patients With Intrahepatic Cholangiocarcinoma In The Usa: Facility Type Is Associated With Margin Status Use Of Lymphadenectomy And Overall Survival Introduction: Intrahepatic cholangiocarcinoma (ICC) remains an uncommon disease with a rising incidence worldwide. We sought to identify trends in therapeutic approaches and differences in patient outcomes based on facility types. \r\n\r\n Methods: Between January 1, 2004, and December 31, 2015, a total of 27,120 patients with histologic diagnosis of ICC were identified in the National Cancer Database and were enrolled in this study. \r\n\r\n Results: The incidence of ICC patients increased from 1194 in 2004 to 3821 in 2015 with an average annual increase of 4.16% (p < 0.001). Median survival of the cohort improved over the last 6 years of the study period (2004-2009: 8.05 months vs. 2010-2015: 9.49 months; p < 0.001). Among surgical patients (n = 5943, 21.9%), the incidence of R0 resection, lymphadenectomy and harvest of ≥6 lymph nodes increased over time (p < 0.001). Positive surgical margins (referent R0: R1, HR 1.49, 95% CI 1.24-1.79, p < 0.001) and treatment at community cancer centers (referent academic centers; HR 1.24, 95% CI 1.04-1.49, p = 0.023) were associated with a worse prognosis. Patients treated at academic centers had higher rates of R0 resection (72.4% vs. 67.7%; p = 0.006) and lymphadenectomy (55.6% vs. 49.5%, p = 0.009) versus community cancer centers. Overall survival was also better at academic versus community cancer programs (median OS: 11 months versus 6 months, respectively; p < 0.001). \r\n\r\n Conclusions: The incidence of ICC has increased over the last 12 years in the USA with a moderate improvement in survival over time. Treatment at academic cancer centers was associated with higher R0 resection and lymphadenectomy rates, as well as improved OS for patients with ICC. STN","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma prognosis varies time depending tumor site pathology background cholangiocarcinoma relatively rare cancer difficult diagnose poor prognosis currently knowledge concerning etiology tumor localization pathological features remains limited present study aimed clarify clinico epidemiologic nature cholangiocarcinoma clinical subtypes using largest regional cancer registry japan methods using regional cancer registry kanagawa prefecture japan estimated three year five year survival rates cholangiocarcinoma patients classified two groups intrahepatic cca extrahepatic cholangiocarcinoma e cca cases hazard ratio subtype including pathological tissue type tumor site calculated results period 1976 2013 14 287 cases cholangiocarcinoma identified prognosis markedly improved 2006 new type chemotherapy cholangiocarcinoma introduced japan patients cca likely younger less likely undergo surgery e cca prognosis cases cca poor compared patients e cca conclusion japan cca likely develop younger people poor prognosis prognosis cca e cca cases markedly improved 2006 present study describes clinico epidemiological features cholangiocarcinoma may useful determining therapeutic strategies disease stn","probabilities":0.7966102,"Title":"Cholangiocarcinoma Prognosis Varies Over Time Depending On Tumor Site And Pathology","Abstract":"Background: Cholangiocarcinoma is a relatively rare cancer that is difficult to diagnose and has a poor prognosis. Currently, knowledge concerning its etiology, tumor localization, and pathological features remains limited. The present study aimed to clarify the clinico-epidemiologic nature of cholangiocarcinoma with its clinical subtypes using the largest regional cancer registry in Japan. \r\n\r\n Methods: Using a regional cancer registry in Kanagawa prefecture, Japan, we estimated three-year and five-year survival rates of cholangiocarcinoma patients, who were classified into two groups: intrahepatic (i-CCA) and extrahepatic cholangiocarcinoma (e-CCA) cases. The hazard ratio for each subtype, including pathological tissue type and tumor site, was calculated. \r\n\r\n Results: During the period from 1976 to 2013, 14,287 cases of cholangiocarcinoma were identified. The prognosis markedly improved after 2006, when a new type of chemotherapy for cholangiocarcinoma was introduced in Japan. Patients with i-CCA were more likely to be younger, and less likely to undergo surgery than those with e-CCA. The prognosis of cases with i-CCA was poor compared to that of patients with e-CCA. \r\n\r\n Conclusion: In Japan, i-CCA was more likely to develop in younger people and to have a poor prognosis. The prognosis of both i-CCA and e-CCA cases markedly improved after 2006. The present study describes clinico-epidemiological features of cholangiocarcinoma that may be useful for determining therapeutic strategies for this disease.","Source":"STN","category":"HUMAN","training_data":"Cholangiocarcinoma Prognosis Varies Over Time Depending On Tumor Site And Pathology Background: Cholangiocarcinoma is a relatively rare cancer that is difficult to diagnose and has a poor prognosis. Currently, knowledge concerning its etiology, tumor localization, and pathological features remains limited. The present study aimed to clarify the clinico-epidemiologic nature of cholangiocarcinoma with its clinical subtypes using the largest regional cancer registry in Japan. \r\n\r\n Methods: Using a regional cancer registry in Kanagawa prefecture, Japan, we estimated three-year and five-year survival rates of cholangiocarcinoma patients, who were classified into two groups: intrahepatic (i-CCA) and extrahepatic cholangiocarcinoma (e-CCA) cases. The hazard ratio for each subtype, including pathological tissue type and tumor site, was calculated. \r\n\r\n Results: During the period from 1976 to 2013, 14,287 cases of cholangiocarcinoma were identified. The prognosis markedly improved after 2006, when a new type of chemotherapy for cholangiocarcinoma was introduced in Japan. Patients with i-CCA were more likely to be younger, and less likely to undergo surgery than those with e-CCA. The prognosis of cases with i-CCA was poor compared to that of patients with e-CCA. \r\n\r\n Conclusion: In Japan, i-CCA was more likely to develop in younger people and to have a poor prognosis. The prognosis of both i-CCA and e-CCA cases markedly improved after 2006. The present study describes clinico-epidemiological features of cholangiocarcinoma that may be useful for determining therapeutic strategies for this disease. STN","prediction_labels":"HUMAN"},{"cleaned":"malignancy lymphoid proliferation primary immune deficiencies hard define hard treat background regarding difficulties recognition management malignancies primary immune deficiencies pids aimed present types risk factors treatment options prognosis cancers specific group methods seventeen patients pid developed malignancies malignant like diseases evaluated demographics clinical features treatment toxicity prognosis results median age malignancy 12 2 years range 2 2 26 lymphoma frequent malignancy n 7 followed adenocarcinoma n 3 squamous cell carcinoma n 2 cholangiocarcinoma n 1 wilms tumor n 1 acute myeloid leukemia n 1 nonneoplastic lymphoproliferation mimicking lymphoma observed five patients total overall survival os 62 5 12 1 os lymphoma 62 2 17 1 found inferior non pid patients lymphoma p 0 001 conclusion patients pids malignancy may occur negatively affect os diagnosis challenging presence nonneoplastic lymphoproliferative disease bone marrow abnormalities awareness susceptibility malignant transformation early diagnosis multidisciplinary approach save patients lives pubmed","probabilities":0.962963,"Title":"Malignancy and lymphoid proliferation in primary immune deficiencies; hard to define, hard to treat","Abstract":"BACKGROUND: Regarding the difficulties in recognition and management of the malignancies in primary immune deficiencies (PIDs), we aimed to present the types, risk factors, treatment options, and prognosis of the cancers in this specific group. METHODS: Seventeen patients with PID who developed malignancies or malignant-like diseases were evaluated for demographics, clinical features, treatment, toxicity, and prognosis. RESULTS: The median age of malignancy was 12.2 years (range, 2.2-26). Lymphoma was the most frequent malignancy (n = 7), followed by adenocarcinoma (n = 3), squamous cell carcinoma (n = 2), cholangiocarcinoma (n = 1), Wilms tumor (n = 1), and acute myeloid leukemia (n = 1). Nonneoplastic lymphoproliferation mimicking lymphoma was observed in five patients. The total overall survival (OS) was 62.5% ± 12.1%. The OS for lymphoma was 62.2% ± 17.1% and found to be inferior to non-PID patients with lymphoma (P = 0.001). CONCLUSION: In patients with PIDs, malignancy may occur and negatively affect the OS. The diagnosis can be challenging in the presence of nonneoplastic lymphoproliferative disease or bone marrow abnormalities. Awareness of susceptibility to malignant transformation and early diagnosis with multidisciplinary approach can save the patients' lives.","Source":"PubMed","category":"HUMAN","training_data":"Malignancy and lymphoid proliferation in primary immune deficiencies; hard to define, hard to treat BACKGROUND: Regarding the difficulties in recognition and management of the malignancies in primary immune deficiencies (PIDs), we aimed to present the types, risk factors, treatment options, and prognosis of the cancers in this specific group. METHODS: Seventeen patients with PID who developed malignancies or malignant-like diseases were evaluated for demographics, clinical features, treatment, toxicity, and prognosis. RESULTS: The median age of malignancy was 12.2 years (range, 2.2-26). Lymphoma was the most frequent malignancy (n = 7), followed by adenocarcinoma (n = 3), squamous cell carcinoma (n = 2), cholangiocarcinoma (n = 1), Wilms tumor (n = 1), and acute myeloid leukemia (n = 1). Nonneoplastic lymphoproliferation mimicking lymphoma was observed in five patients. The total overall survival (OS) was 62.5% ± 12.1%. The OS for lymphoma was 62.2% ± 17.1% and found to be inferior to non-PID patients with lymphoma (P = 0.001). CONCLUSION: In patients with PIDs, malignancy may occur and negatively affect the OS. The diagnosis can be challenging in the presence of nonneoplastic lymphoproliferative disease or bone marrow abnormalities. Awareness of susceptibility to malignant transformation and early diagnosis with multidisciplinary approach can save the patients' lives. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathologic prognostic significance cd24 gallbladder carcinoma cd24 small cell surface protein emerged novel oncogene prognostic factor poor outcomes many human cancers however association cd24 expression pattern gallbladder carcinoma patients survival reported shed light problem performed analysis relationship cd24 expression prognostic parameters gallbladder carcinoma cd24 expression examined immunohistochemically paraffin embedded tissue specimens 207 patients underwent surgical treatment gallbladder carcinoma period january 2004 may 2009 cd24 positive expression found 78 7 163 207 tumor samples tended associated positively tumor histological grades pt stages kaplan meier curves showed cd24 positive expression significantly related decreased overall survival p 0 01 multivariate analysis including cd24 expression pt stage tumor grade resection margin involvement showed cd24 positive expression independent prognostic marker gallbladder carcinoma p 0 02 relative risk 1 6 data demonstrate first time cd24 important marker malignancy poor prognosis gallbladder carcinoma detection combined cancerous staging may increase ability investigators predict prognosis patients gallbladder carcinoma furthermore cd24 antigen represents attractive target specific therapies monoclonal antibodies patients cd24 overexpressing gallbladder carcinoma detection cd24 may help clinicians select patients likely benefit novel molecular therapies stn","probabilities":1.0,"Title":"Clinicopathologic And Prognostic Significance Of Cd24 In Gallbladder Carcinoma","Abstract":"CD24, a small cell surface protein, has emerged as a novel oncogene and prognostic factor for poor outcomes in many human cancers. However, the association of CD24 expression pattern in gallbladder carcinoma with patients' survival has not been reported. To shed light on this problem, we performed an analysis on the relationship between CD24 expression and prognostic parameters in gallbladder carcinoma. CD24 expression was examined immunohistochemically on paraffin-embedded tissue specimens from 207 patients who underwent surgical treatment for gallbladder carcinoma in the period between January 2004 and May 2009. CD24 positive expression was found in 78.7% (163/207) of the tumor samples. It tended to be associated positively with tumor histological grades and pT stages. Kaplan-Meier curves showed that CD24 positive expression was significantly related to decreased overall survival (p < 0.01). Multivariate analysis, including CD24 expression, pT stage, tumor grade, and resection margin involvement, showed that CD24 positive expression was an independent prognostic marker in gallbladder carcinoma (p = 0.02; relative risk = 1.6). Our data demonstrate for the first time that CD24 is an important marker of malignancy and poor prognosis in gallbladder carcinoma. Its detection combined with cancerous staging may increase the ability of investigators to predict the prognosis of patients with gallbladder carcinoma. Furthermore, the CD24 antigen represents an attractive target for specific therapies with monoclonal antibodies in patients with CD24-overexpressing gallbladder carcinoma, so the detection of CD24 may help clinicians select patients likely to benefit from novel molecular therapies.","Source":"STN","category":"HUMAN","training_data":"Clinicopathologic And Prognostic Significance Of Cd24 In Gallbladder Carcinoma CD24, a small cell surface protein, has emerged as a novel oncogene and prognostic factor for poor outcomes in many human cancers. However, the association of CD24 expression pattern in gallbladder carcinoma with patients' survival has not been reported. To shed light on this problem, we performed an analysis on the relationship between CD24 expression and prognostic parameters in gallbladder carcinoma. CD24 expression was examined immunohistochemically on paraffin-embedded tissue specimens from 207 patients who underwent surgical treatment for gallbladder carcinoma in the period between January 2004 and May 2009. CD24 positive expression was found in 78.7% (163/207) of the tumor samples. It tended to be associated positively with tumor histological grades and pT stages. Kaplan-Meier curves showed that CD24 positive expression was significantly related to decreased overall survival (p < 0.01). Multivariate analysis, including CD24 expression, pT stage, tumor grade, and resection margin involvement, showed that CD24 positive expression was an independent prognostic marker in gallbladder carcinoma (p = 0.02; relative risk = 1.6). Our data demonstrate for the first time that CD24 is an important marker of malignancy and poor prognosis in gallbladder carcinoma. Its detection combined with cancerous staging may increase the ability of investigators to predict the prognosis of patients with gallbladder carcinoma. Furthermore, the CD24 antigen represents an attractive target for specific therapies with monoclonal antibodies in patients with CD24-overexpressing gallbladder carcinoma, so the detection of CD24 may help clinicians select patients likely to benefit from novel molecular therapies. STN","prediction_labels":"HUMAN"},{"cleaned":"establishment characterization cell line eh gb2 derived hepatic metastasis gallbladder cancer gallbladder cancer fatal neoplasia extremely low survival rate liver invasion metastasis common causes death however metastatic mechanism still unclear effective treatment methods available provide comprehensive profound approaches investigating metastatic mechanism treatment methods new cell lines derived liver metastasis urgently needed hepatic metastasis lesion obtained 65 year old patient treated using primary culture method establish novel gallbladder cancer cell line different vitro vivo methods used characterize phenotypes cell line gallbladder cancer cell line named eh gb2 roughly 48 h doubling time cell line represents stronger colony formation migration abilities control group cells showed complicated chromosomal abnormalities eh gb2 cells showed epithelial mesenchymal transition emt mrna expression levels e cadherin integrin decreased vimentin snail twist matrix metalloproteinase 1 mmp 1 mmp 2 increased comparison control cells vivo study demonstrated eh gb2 cells show significant tumorigenicity nude mice eh gb2 established gallbladder cancer cell line useful future studies gallbladder cancer development progression metastasis therapy stn","probabilities":0.9467213,"Title":"Establishment And Characterization Of A Cell Line Eh-Gb2 Derived From Hepatic Metastasis Of Gallbladder Cancer","Abstract":"Gallbladder cancer is a fatal neoplasia with an extremely low survival rate. Liver invasion and metastasis are the most common causes of death; however, the metastatic mechanism is still unclear, and no effective treatment methods are available. To provide comprehensive and profound approaches in investigating the metastatic mechanism and treatment methods, new cell lines derived from liver metastasis are urgently needed. A hepatic metastasis lesion was obtained from a 65-year-old patient, and was treated using a primary culture method to establish a novel gallbladder cancer cell line. Different in vitro/in vivo methods were used to characterize the phenotypes of this cell line. The gallbladder cancer cell line was named EH-GB2, with a roughly 48-h doubling time. The cell line represents stronger colony formation and migration abilities than the control group. The cells showed complicated chromosomal abnormalities. EH-GB2 cells showed epithelial-to-mesenchymal transition (EMT) and the mRNA expression levels of E-cadherin and integrin were decreased, and those of vimentin, Snail, Twist, matrix metalloproteinase-1 (MMP-1) and MMP-2 were increased in comparison with control cells. The in vivo study demonstrated that EH-GB2 cells show significant tumorigenicity in nude mice. The EH-GB2 established gallbladder cancer cell line is useful for future studies of gallbladder cancer development, progression, metastasis and therapy.","Source":"STN","category":"ANIMAL","training_data":"Establishment And Characterization Of A Cell Line Eh-Gb2 Derived From Hepatic Metastasis Of Gallbladder Cancer Gallbladder cancer is a fatal neoplasia with an extremely low survival rate. Liver invasion and metastasis are the most common causes of death; however, the metastatic mechanism is still unclear, and no effective treatment methods are available. To provide comprehensive and profound approaches in investigating the metastatic mechanism and treatment methods, new cell lines derived from liver metastasis are urgently needed. A hepatic metastasis lesion was obtained from a 65-year-old patient, and was treated using a primary culture method to establish a novel gallbladder cancer cell line. Different in vitro/in vivo methods were used to characterize the phenotypes of this cell line. The gallbladder cancer cell line was named EH-GB2, with a roughly 48-h doubling time. The cell line represents stronger colony formation and migration abilities than the control group. The cells showed complicated chromosomal abnormalities. EH-GB2 cells showed epithelial-to-mesenchymal transition (EMT) and the mRNA expression levels of E-cadherin and integrin were decreased, and those of vimentin, Snail, Twist, matrix metalloproteinase-1 (MMP-1) and MMP-2 were increased in comparison with control cells. The in vivo study demonstrated that EH-GB2 cells show significant tumorigenicity in nude mice. The EH-GB2 established gallbladder cancer cell line is useful for future studies of gallbladder cancer development, progression, metastasis and therapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"patients recurrent biliary tract cancer better prognosis unresectable disease retrospective analysis multi institutional experience patients advanced biliary tract cancer received palliative chemotherapy background prognostic factors patients advanced biliary tract cancer btc received palliative chemotherapy fully established especially status unresectable recurrent disease well studied small number patients recurrent btc previous studies methods multicenter retrospective study conducted 18 institutions japan retrospectively reviewed data regarding 403 patients pathologically proven btc received palliative chemotherapy april 2006 march 2009 one hundred ninety two patients recurrent btc included univariate multivariate analyses performed identify prognostic factors results median overall survival significantly longer recurrent btc patients unresectable btc patients 398 days vs 323 days p 0 004 adjustment using multivariate analysis status recurrent unresectable disease remained independent prognostic factor hazard ratio 1 33 95 confidence interval 1 04 1 70 p 0 022 addition performance status extent disease carbohydrate antigen 19 9 levels carcinoembryonic antigen levels conclusions status unresectable recurrent disease shown independent prognostic factor btc patients result may help predict life expectancy btc patients design future clinical trials evaluating palliative chemotherapy btc pubmed","probabilities":0.9799733,"Title":"Patients with recurrent biliary tract cancer have a better prognosis than those with unresectable disease: retrospective analysis of a multi-institutional experience with patients of advanced biliary tract cancer who received palliative chemotherapy","Abstract":"BACKGROUND: Prognostic factors for patients with advanced biliary tract cancer (BTC) who received palliative chemotherapy have not been fully established. Especially, the status of unresectable/recurrent disease has not been well studied because of a small number of patients with recurrent BTC in previous studies. METHODS: This multicenter retrospective study was conducted in 18 institutions in Japan. We retrospectively reviewed data regarding 403 patients with pathologically proven BTC who received palliative chemotherapy between April 2006 and March 2009. One hundred and ninety-two patients with recurrent BTC were included. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: The median overall survival was significantly longer in the recurrent BTC patients than in the unresectable BTC patients (398 days vs. 323 days, P = 0.004). After adjustment using multivariate analysis, the status of recurrent/unresectable disease remained an independent prognostic factor (hazard ratio 1.33, 95% confidence interval 1.04-1.70, P = 0.022) in addition to performance status, extent of disease, carbohydrate antigen 19-9 levels, and carcinoembryonic antigen levels. CONCLUSIONS: The status of unresectable/recurrent disease was shown as an independent prognostic factor in the BTC patients. This result may help to predict life expectancy of BTC patients and design future clinical trials evaluating palliative chemotherapy in BTC.","Source":"PubMed","category":"HUMAN","training_data":"Patients with recurrent biliary tract cancer have a better prognosis than those with unresectable disease: retrospective analysis of a multi-institutional experience with patients of advanced biliary tract cancer who received palliative chemotherapy BACKGROUND: Prognostic factors for patients with advanced biliary tract cancer (BTC) who received palliative chemotherapy have not been fully established. Especially, the status of unresectable/recurrent disease has not been well studied because of a small number of patients with recurrent BTC in previous studies. METHODS: This multicenter retrospective study was conducted in 18 institutions in Japan. We retrospectively reviewed data regarding 403 patients with pathologically proven BTC who received palliative chemotherapy between April 2006 and March 2009. One hundred and ninety-two patients with recurrent BTC were included. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: The median overall survival was significantly longer in the recurrent BTC patients than in the unresectable BTC patients (398 days vs. 323 days, P = 0.004). After adjustment using multivariate analysis, the status of recurrent/unresectable disease remained an independent prognostic factor (hazard ratio 1.33, 95% confidence interval 1.04-1.70, P = 0.022) in addition to performance status, extent of disease, carbohydrate antigen 19-9 levels, and carcinoembryonic antigen levels. CONCLUSIONS: The status of unresectable/recurrent disease was shown as an independent prognostic factor in the BTC patients. This result may help to predict life expectancy of BTC patients and design future clinical trials evaluating palliative chemotherapy in BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long non coding rna myocardial infarction associated transcript promotes proliferation cholangiocarcinoma cells targeting mir 551b 3p ccnd1 axis accumulating reports demonstrated long non coding rnas lncrnas play critical roles occurrence metastasis cholangiocarcinoma cca lncrna myocardial infarction associated transcript miat widely reported hepatocellular carcinoma pancreatic cancer colorectal cancer relationship miat cca progression yet investigated present study found expression miat cca tissues prominently higher normal bile duct tissues moreover tcga chol data gepia platform revealed upregulated expression miat cca tissues additionally quantitative real time pcr results showed miat expression increased cca cell lines compared human intrahepatic biliary epithelial cell line functionally miat knockdown significantly inhibited cell proliferation induced g0 g1 phase arrest well apoptosis hucct 1 qbc939 cells conversely ectopic expression miat obviously facilitated proliferation cell cycle progression apoptosis resistance rbe cells mechanistically miat directly interacted mir 551b 3p inversely modulated mir 551 3p level cca cells furthermore miat knockdown reduced expression cyclin d1 ccnd1 rescued mir 551b 3p silencing hucct 1 cells importantly ccnd1 restoration partially reversed miat knockdown induced proliferation inhibition g0 g1 phase arrest apoptosis hucct 1 cells conclusion miat frequently overexpressed cca miat contributed growth cca cells targeting mir 551b 3p ccnd1 axis stn","probabilities":0.9467213,"Title":"Long Non-Coding Rna Myocardial Infarction Associated Transcript Promotes The Proliferation Of Cholangiocarcinoma Cells By Targeting Mir-551B-3P/Ccnd1 Axis","Abstract":"Accumulating reports have demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the occurrence and metastasis of cholangiocarcinoma (CCA). LncRNA myocardial infarction associated transcript (MIAT) has been widely reported in hepatocellular carcinoma, pancreatic cancer and colorectal cancer, but the relationship between MIAT and CCA progression has not yet been investigated. In the present study, we found that the expression of MIAT in CCA tissues was prominently higher than that in normal bile duct tissues. Moreover, TCGA-CHOL data in the GEPIA platform further revealed the upregulated expression of MIAT in CCA tissues. Additionally, quantitative real-time PCR results showed that MIAT expression was increased in CCA cell lines compared to the human intrahepatic biliary epithelial cell line. Functionally, MIAT knockdown significantly inhibited cell proliferation and induced G0/G1 phase arrest as well as apoptosis in HuCCT-1 and QBC939 cells. Conversely, ectopic expression of MIAT obviously facilitated the proliferation, cell cycle progression and apoptosis resistance of RBE cells. Mechanistically, MIAT directly interacted with miR-551b-3p and inversely modulated miR-551-3p level in CCA cells. Furthermore, MIAT knockdown reduced the expression of cyclin D1 (CCND1), which was rescued by miR-551b-3p silencing in HuCCT-1 cells. Importantly, CCND1 restoration partially reversed MIAT knockdown-induced proliferation inhibition, G0/G1 phase arrest and apoptosis in HuCCT-1 cells. In conclusion, MIAT was frequently overexpressed in CCA. MIAT contributed to the growth of CCA cells by targeting miR-551b-3p/CCND1 axis.","Source":"STN","category":"ANIMAL","training_data":"Long Non-Coding Rna Myocardial Infarction Associated Transcript Promotes The Proliferation Of Cholangiocarcinoma Cells By Targeting Mir-551B-3P/Ccnd1 Axis Accumulating reports have demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the occurrence and metastasis of cholangiocarcinoma (CCA). LncRNA myocardial infarction associated transcript (MIAT) has been widely reported in hepatocellular carcinoma, pancreatic cancer and colorectal cancer, but the relationship between MIAT and CCA progression has not yet been investigated. In the present study, we found that the expression of MIAT in CCA tissues was prominently higher than that in normal bile duct tissues. Moreover, TCGA-CHOL data in the GEPIA platform further revealed the upregulated expression of MIAT in CCA tissues. Additionally, quantitative real-time PCR results showed that MIAT expression was increased in CCA cell lines compared to the human intrahepatic biliary epithelial cell line. Functionally, MIAT knockdown significantly inhibited cell proliferation and induced G0/G1 phase arrest as well as apoptosis in HuCCT-1 and QBC939 cells. Conversely, ectopic expression of MIAT obviously facilitated the proliferation, cell cycle progression and apoptosis resistance of RBE cells. Mechanistically, MIAT directly interacted with miR-551b-3p and inversely modulated miR-551-3p level in CCA cells. Furthermore, MIAT knockdown reduced the expression of cyclin D1 (CCND1), which was rescued by miR-551b-3p silencing in HuCCT-1 cells. Importantly, CCND1 restoration partially reversed MIAT knockdown-induced proliferation inhibition, G0/G1 phase arrest and apoptosis in HuCCT-1 cells. In conclusion, MIAT was frequently overexpressed in CCA. MIAT contributed to the growth of CCA cells by targeting miR-551b-3p/CCND1 axis. STN","prediction_labels":"ANIMAL"},{"cleaned":"epidemiological trends incidence mortality hepatobiliary cancers germany objective marked changes frequency hepatobiliary malignancies notably hepatocellular carcinoma hcc intrahepatic cholangiocarcinoma icc observed different populations data reported germany aimed provide epidemiological data recent trends liver related mortality specifically mortality hepatobiliary malignancies germany material methods used incidence mortality data determine changes frequency malignant non malignant liver disease germany past 30 years results overall liver disease mortality slightly declined germany deaths hepatobiliary malignancies declined women remained constant men among hepatobiliary malignancies icc stands mortality tripled men women 1998 2008 mirrored marked increase new cases reported local cancer registries incidence time period hcc extrahepatic cholangiocarcinoma ecc remained largely constant gall bladder cancers gbc declined twofold rapid rise icc line finding different regions worldwide contrast recent data denmark france two germany direct neighbors conclusions incidence mortality icc rising markedly germany risk factors underlying trend yet unclear stn","probabilities":0.9799733,"Title":"Epidemiological Trends In Incidence And Mortality Of Hepatobiliary Cancers In Germany","Abstract":"Objective: While marked changes in the frequency of hepatobiliary malignancies, most notably hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), have been observed in different populations, no such data have been reported for Germany. We aimed to provide epidemiological data on recent trends in liver-related mortality, specifically mortality from hepatobiliary malignancies, in Germany. \r\n\r\n Material and methods: We used incidence and mortality data to determine changes in the frequency of malignant and non-malignant liver disease in Germany over the past 30 years. \r\n\r\n Results: While overall liver disease mortality has slightly declined in Germany, deaths from hepatobiliary malignancies have declined in women, but remained constant in men. Among hepatobiliary malignancies, ICC stands out, because mortality has more than tripled both in men and women between 1998 and 2008. This is mirrored by a marked increase in new cases reported to local cancer registries, that is, incidence. Over the same time period, HCC and extrahepatic cholangiocarcinoma (ECC) have remained largely constant while gall bladder cancers (GBC) have declined twofold. The rapid rise in ICC is in line with finding from different regions worldwide, but in contrast to recent data from Denmark and France, two of Germany's direct neighbors. \r\n\r\n Conclusions: The incidence of and mortality from ICC are rising markedly in Germany. The risk factors underlying this trend are as yet unclear.","Source":"STN","category":"HUMAN","training_data":"Epidemiological Trends In Incidence And Mortality Of Hepatobiliary Cancers In Germany Objective: While marked changes in the frequency of hepatobiliary malignancies, most notably hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), have been observed in different populations, no such data have been reported for Germany. We aimed to provide epidemiological data on recent trends in liver-related mortality, specifically mortality from hepatobiliary malignancies, in Germany. \r\n\r\n Material and methods: We used incidence and mortality data to determine changes in the frequency of malignant and non-malignant liver disease in Germany over the past 30 years. \r\n\r\n Results: While overall liver disease mortality has slightly declined in Germany, deaths from hepatobiliary malignancies have declined in women, but remained constant in men. Among hepatobiliary malignancies, ICC stands out, because mortality has more than tripled both in men and women between 1998 and 2008. This is mirrored by a marked increase in new cases reported to local cancer registries, that is, incidence. Over the same time period, HCC and extrahepatic cholangiocarcinoma (ECC) have remained largely constant while gall bladder cancers (GBC) have declined twofold. The rapid rise in ICC is in line with finding from different regions worldwide, but in contrast to recent data from Denmark and France, two of Germany's direct neighbors. \r\n\r\n Conclusions: The incidence of and mortality from ICC are rising markedly in Germany. The risk factors underlying this trend are as yet unclear. STN","prediction_labels":"HUMAN"},{"cleaned":"role sarcopenia patients intrahepatic cholangiocarcinoma prognostic marker hyped parameter background aims sarcopenia emerged prognostic parameter numerous cancer entities current research favours role determining factor overall survival os patients intrahepatic cholangiocarcinoma icc however unclear whether sarcopenia truly independent survival predictor combined established prognostic factors methods 1997 2018 417 patients histopathologically confirmed icc referred centre 293 included study cross sectional imaging laboratory examinations histopathological reports retrospectively analysed psoas muscle index pmi easy measure marker sarcopenia calculated using optimal stratification sex specific pmi cut offs calculated tested hazard regression models previously published risk factors entire cohort within resected non resected subgroups results median os patients low respectively high pmi 23 5 34 5 months resected subgroup p 0 008 5 1 7 8 months p 0 01 non resected subgroup multivariate hazard regression models entire cohort low pmi exhibited independent predictive value p 0 01 translobar tumour spread p 0 005 extrahepatic extension p 0 03 tumour boundary type p 0 001 carbohydrate antigen 19 9 ca 19 9 levels p 0 001 alkaline phosphatase levels p 0 001 distant metastasis p 0 001 subgroup analyses low pmi remained predictive among non resected patients p 0 03 lost predictive value among resected patients p 0 15 conclusions psoas muscle index strongly predicted os univariate analysis however addition established risk factors eliminated predictive value among resected patients thus resection deemed oncologically reasonable patients excluded surgery sarcopenia alone stn","probabilities":0.9799733,"Title":"The Role Of Sarcopenia In Patients With Intrahepatic Cholangiocarcinoma: Prognostic Marker Or Hyped Parameter?","Abstract":"Background & aims: Sarcopenia has emerged as a prognostic parameter in numerous cancer entities. Current research favours its role as a determining factor for overall survival (OS) in patients with intrahepatic cholangiocarcinoma (ICC); however, it is unclear whether sarcopenia is a truly independent survival predictor if combined with established prognostic factors. \r\n\r\n Methods: Between 1997-2018, 417 patients with histopathologically confirmed ICC were referred to our centre, of whom 293 were included in this study. Cross-sectional imaging, laboratory examinations and histopathological reports were retrospectively analysed. Psoas muscle index (PMI) as easy-to-measure marker of sarcopenia was calculated. Using optimal stratification, sex-specific PMI cut-offs were calculated and tested in hazard regression models against previously published risk factors-for the entire cohort, and within resected and non-resected subgroups. \r\n\r\n Results: Median OS for patients with low respectively high PMI was 23.5 and 34.5 months in the resected subgroup (P = 0.008) and 5.1 and 7.8 months (P = 0.01) in the non-resected subgroup. In multivariate hazard regression models for the entire cohort, low PMI exhibited independent predictive value (P = 0.01) as did translobar tumour spread (P = 0.005), extrahepatic extension (P = 0.03), tumour boundary type (P < 0.001), carbohydrate antigen 19-9 (CA 19-9) levels (P = 0.001), alkaline phosphatase levels (P = 0.001) and distant metastasis (P < 0.001). In subgroup analyses, low PMI remained predictive among non-resected patients (P = 0.03), but lost its predictive value among resected patients (P = 0.15). \r\n\r\n Conclusions: Psoas muscle index strongly predicted OS in univariate analysis. However, addition of established risk factors eliminated its predictive value among resected patients. Thus, when resection is deemed oncologically reasonable, patients should not be excluded from surgery because of sarcopenia alone.","Source":"STN","category":"HUMAN","training_data":"The Role Of Sarcopenia In Patients With Intrahepatic Cholangiocarcinoma: Prognostic Marker Or Hyped Parameter? Background & aims: Sarcopenia has emerged as a prognostic parameter in numerous cancer entities. Current research favours its role as a determining factor for overall survival (OS) in patients with intrahepatic cholangiocarcinoma (ICC); however, it is unclear whether sarcopenia is a truly independent survival predictor if combined with established prognostic factors. \r\n\r\n Methods: Between 1997-2018, 417 patients with histopathologically confirmed ICC were referred to our centre, of whom 293 were included in this study. Cross-sectional imaging, laboratory examinations and histopathological reports were retrospectively analysed. Psoas muscle index (PMI) as easy-to-measure marker of sarcopenia was calculated. Using optimal stratification, sex-specific PMI cut-offs were calculated and tested in hazard regression models against previously published risk factors-for the entire cohort, and within resected and non-resected subgroups. \r\n\r\n Results: Median OS for patients with low respectively high PMI was 23.5 and 34.5 months in the resected subgroup (P = 0.008) and 5.1 and 7.8 months (P = 0.01) in the non-resected subgroup. In multivariate hazard regression models for the entire cohort, low PMI exhibited independent predictive value (P = 0.01) as did translobar tumour spread (P = 0.005), extrahepatic extension (P = 0.03), tumour boundary type (P < 0.001), carbohydrate antigen 19-9 (CA 19-9) levels (P = 0.001), alkaline phosphatase levels (P = 0.001) and distant metastasis (P < 0.001). In subgroup analyses, low PMI remained predictive among non-resected patients (P = 0.03), but lost its predictive value among resected patients (P = 0.15). \r\n\r\n Conclusions: Psoas muscle index strongly predicted OS in univariate analysis. However, addition of established risk factors eliminated its predictive value among resected patients. Thus, when resection is deemed oncologically reasonable, patients should not be excluded from surgery because of sarcopenia alone. STN","prediction_labels":"HUMAN"},{"cleaned":"biliary tumor ablation photodynamic therapy radiofrequency ablation within past two decades major progress made biliary endoscopy stenting ablative therapy primary goal patients malignant biliary lesions candidates surgery provide localized efficient necrosis lesions article summarizes current literature biliary tumor ablation photodynamic therapy radiofrequency ablation prognosis treatment technique potential complications treatment efficacy controversies discussed pubmed","probabilities":0.9799733,"Title":"Biliary Tumor Ablation with Photodynamic Therapy and Radiofrequency Ablation","Abstract":"Within the past two decades, major progress has been made in biliary endoscopy both with stenting and with ablative therapy. A primary goal in patients with malignant biliary lesions who are not candidates for surgery is to provide localized and efficient necrosis of the lesions. This article summarizes the current literature on biliary tumor ablation with photodynamic therapy and radiofrequency ablation. Prognosis, treatment technique, potential complications, treatment efficacy, and controversies are discussed.","Source":"PubMed","category":"HUMAN","training_data":"Biliary Tumor Ablation with Photodynamic Therapy and Radiofrequency Ablation Within the past two decades, major progress has been made in biliary endoscopy both with stenting and with ablative therapy. A primary goal in patients with malignant biliary lesions who are not candidates for surgery is to provide localized and efficient necrosis of the lesions. This article summarizes the current literature on biliary tumor ablation with photodynamic therapy and radiofrequency ablation. Prognosis, treatment technique, potential complications, treatment efficacy, and controversies are discussed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment prognosis patients intrahepatic cholangiocarcinoma systematic review meta analysis importance data outcomes following surgical management intrahepatic cholangiocarcinoma icc limited incidence icc increasing poor prognosis consensus reached regarding optimal treatment modalities objective systematically review synthesize available evidence regarding treatment prognosis patients icc data sources pubmed database searched relevant articles published january 1 2000 april 1 2013 study selection studies assessing predictors survival recurrence patients undergoing curative intent surgical treatment icc included small series studies reporting mixed types cholangiocarcinoma exclusively hepatolithiasis associated cholangiocarcinoma published language english french german italian greek excluded fifty seven 960 articles therefore analyzed data extraction synthesis data preoperative intraoperative postoperative variables extracted 3 independent reviewers multiple studies reporting population excluded data pooled using random effects model main outcomes measures hypothesized preoperative variables tumor characteristics affect patient survival outcomes study overall survival recurrence free survival hypothesis formulated data collection results fifty seven studies 4756 patients included review median patient age ranged 49 67 years 57 male patients solitary 69 large median size 4 5 8 0 cm tumor mass forming type 86 approximately one third patients lymph node metastasis 34 vascular 38 perineural 29 biliary invasion 29 underwent major hepatectomy 82 often accompanied lymphadenectomy 67 sometimes extrahepatic bile duct resection 23 median 5 year overall survival os generally approximately 28 months range 9 53 months 30 range 5 56 respectively factors predicting shorter os included large tumor size multiple tumors lymph node metastasis vascular invasion adjuvant chemotherapy radiotherapy appear beneficial seven studies 2132 patients provided data meta analysis factors associated shorter os included older age pooled hazard ratio 1 10 95 ci 1 03 1 17 larger tumor size 1 09 1 02 1 16 presence multiple tumors 1 70 1 43 2 02 lymph node metastasis 2 09 1 80 2 43 vascular invasion 1 87 1 44 2 42 poor tumor differentiation 1 41 1 17 1 71 conclusions relevance prognosis icc dictated mainly tumor factors future research focus usefulness adjuvant treatment well multidisciplinary treatment modalities pubmed","probabilities":0.9799733,"Title":"Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma: Systematic Review and Meta-analysis","Abstract":"IMPORTANCE: Data on outcomes following surgical management of intrahepatic cholangiocarcinoma (ICC) are limited. The incidence of ICC is increasing and it has a poor prognosis. No consensus has been reached regarding the optimal treatment modalities. OBJECTIVE: To systematically review and synthesize the available evidence regarding treatment and prognosis in patients with ICC. DATA SOURCES: The PubMed database was searched for relevant articles published between January 1, 2000, and April 1, 2013. STUDY SELECTION: Only studies assessing predictors of survival or recurrence in patients undergoing curative-intent surgical treatment of ICC were included. Small series, studies reporting on mixed types of cholangiocarcinoma, or exclusively on hepatolithiasis-associated cholangiocarcinoma, and those published in a language other than English, French, German, Italian, or Greek, were excluded. Fifty-seven of 960 articles were therefore analyzed. DATA EXTRACTION AND SYNTHESIS: Data on preoperative, intraoperative, and postoperative variables were extracted by 3 independent reviewers. Multiple studies reporting on the same population were excluded. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: We hypothesized that preoperative variables and tumor characteristics affect patient survival. The outcomes of the study were overall survival and recurrence-free survival. The hypothesis was formulated before data collection. RESULTS: Fifty-seven studies (4756 patients) were included in the review. Median patient age ranged from 49 to 67 years, and 57% were male. Most patients had a solitary (69%), large (median size, 4.5-8.0 cm) tumor of the mass-forming type (86%). Approximately one-third of the patients had lymph node metastasis (34%) or vascular (38%), perineural (29%), or biliary invasion (29%). Most underwent a major hepatectomy (82%), often accompanied by lymphadenectomy (67%) and sometimes by extrahepatic bile duct resection (23%). Median and 5-year overall survival (OS) generally were approximately 28 months (range, 9-53 months) and 30% (range, 5%-56%), respectively; factors predicting shorter OS included large tumor size, multiple tumors, lymph node metastasis, and vascular invasion. Adjuvant chemotherapy or radiotherapy did not appear to be beneficial. Seven studies (2132 patients) provided data for the meta-analysis. Factors associated with shorter OS included older age (pooled hazard ratio, 1.10; 95% CI, 1.03-1.17), larger tumor size (1.09; 1.02-1.16), presence of multiple tumors (1.70; 1.43-2.02), lymph node metastasis (2.09; 1.80-2.43), vascular invasion (1.87; 1.44-2.42), and poor tumor differentiation (1.41; 1.17-1.71). CONCLUSIONS AND RELEVANCE: The prognosis of ICC is dictated mainly by tumor factors. Future research could focus on the usefulness of adjuvant treatment as well as other multidisciplinary treatment modalities.","Source":"PubMed","category":"HUMAN","training_data":"Treatment and Prognosis for Patients With Intrahepatic Cholangiocarcinoma: Systematic Review and Meta-analysis IMPORTANCE: Data on outcomes following surgical management of intrahepatic cholangiocarcinoma (ICC) are limited. The incidence of ICC is increasing and it has a poor prognosis. No consensus has been reached regarding the optimal treatment modalities. OBJECTIVE: To systematically review and synthesize the available evidence regarding treatment and prognosis in patients with ICC. DATA SOURCES: The PubMed database was searched for relevant articles published between January 1, 2000, and April 1, 2013. STUDY SELECTION: Only studies assessing predictors of survival or recurrence in patients undergoing curative-intent surgical treatment of ICC were included. Small series, studies reporting on mixed types of cholangiocarcinoma, or exclusively on hepatolithiasis-associated cholangiocarcinoma, and those published in a language other than English, French, German, Italian, or Greek, were excluded. Fifty-seven of 960 articles were therefore analyzed. DATA EXTRACTION AND SYNTHESIS: Data on preoperative, intraoperative, and postoperative variables were extracted by 3 independent reviewers. Multiple studies reporting on the same population were excluded. Data were pooled using a random-effects model. MAIN OUTCOMES AND MEASURES: We hypothesized that preoperative variables and tumor characteristics affect patient survival. The outcomes of the study were overall survival and recurrence-free survival. The hypothesis was formulated before data collection. RESULTS: Fifty-seven studies (4756 patients) were included in the review. Median patient age ranged from 49 to 67 years, and 57% were male. Most patients had a solitary (69%), large (median size, 4.5-8.0 cm) tumor of the mass-forming type (86%). Approximately one-third of the patients had lymph node metastasis (34%) or vascular (38%), perineural (29%), or biliary invasion (29%). Most underwent a major hepatectomy (82%), often accompanied by lymphadenectomy (67%) and sometimes by extrahepatic bile duct resection (23%). Median and 5-year overall survival (OS) generally were approximately 28 months (range, 9-53 months) and 30% (range, 5%-56%), respectively; factors predicting shorter OS included large tumor size, multiple tumors, lymph node metastasis, and vascular invasion. Adjuvant chemotherapy or radiotherapy did not appear to be beneficial. Seven studies (2132 patients) provided data for the meta-analysis. Factors associated with shorter OS included older age (pooled hazard ratio, 1.10; 95% CI, 1.03-1.17), larger tumor size (1.09; 1.02-1.16), presence of multiple tumors (1.70; 1.43-2.02), lymph node metastasis (2.09; 1.80-2.43), vascular invasion (1.87; 1.44-2.42), and poor tumor differentiation (1.41; 1.17-1.71). CONCLUSIONS AND RELEVANCE: The prognosis of ICC is dictated mainly by tumor factors. Future research could focus on the usefulness of adjuvant treatment as well as other multidisciplinary treatment modalities. PubMed","prediction_labels":"HUMAN"},{"cleaned":"fyn knockdown inhibits migration invasion cholangiocarcinoma activated ampk mtor signaling pathway cholangiocarcinoma cca rare fatal tumor previous decades steady increase incidence mortality rates tumor worldwide metastasis regarded major factor contributes poor prognosis cca patients studies therefore aim develop novel therapeutic targets control cca metastasis fyn known enhance expression promote metastasis various cancers including pancreatic cancer prostate cancer colorectal cancer however exact function mechanism fyn cca metastasis remains unclear present study mrna protein expression levels fyn amp activated protein kinase ampk phosphorylated p ampk mammalian target rapamycin mtor p mtor measured using reverse transcription quantitative polymerase chain reaction western blot analysis cca tissues cell lines addition transwell assays used determine migratory invasive abilities human cca qbc939 following transfection present study found fyn overexpressed cca cell lines fyn knockdown inhibited cca cell migration invasion furthermore demonstrated fyn knockdown induces phosphorylation ampk inhibits downstream phosphorylation mtor activate ampk mtor signaling pathway compound c ampk inhibitor inhibited ampk mtor signaling pathway reversed effect fyn knockdown migration invasion cca cells conclusion present study suggests fyn knockdown inhibits cell migration invasion regulating ampk mtor signaling pathway cca cell lines fyn knockdown potential target anti cca therapy stn","probabilities":0.9467213,"Title":"Fyn Knockdown Inhibits Migration And Invasion In Cholangiocarcinoma Through The Activated Ampk/Mtor Signaling Pathway","Abstract":"Cholangiocarcinoma (CCA) is a rare and fatal tumor. In previous decades, there has been a steady increase in the incidence and mortality rates of this tumor worldwide. Metastasis is regarded as the major factor that contributes to poor prognosis in CCA patients. Studies therefore aim to develop novel therapeutic targets to control CCA metastasis. Fyn is known to enhance expression and promote metastasis in various cancers, including pancreatic cancer, prostate cancer and colorectal cancer. However, the exact function and mechanism of Fyn in CCA metastasis remains unclear. In the present study, mRNA and protein expression levels of Fyn, AMP-activated protein kinase (AMPK), phosphorylated (p-)AMPK, mammalian target of rapamycin (mTOR) and p-mTOR were measured, using the reverse transcription-quantitative polymerase chain reaction and western blot analysis, in CCA tissues and cell lines. In addition, Transwell assays were used to determine the migratory and invasive abilities of human CCA QBC939, following transfection. In the present study, it was found that Fyn was overexpressed in CCA cell lines. Fyn knockdown inhibited CCA cell migration and invasion. Furthermore, it was demonstrated that Fyn knockdown induces phosphorylation of AMPK, inhibits downstream phosphorylation of mTOR, and activate the AMPK/mTOR signaling pathway. Compound C, an AMPK inhibitor, inhibited the AMPK/mTOR signaling pathway, and reversed the effect of Fyn knockdown on migration and invasion of CCA cells. In conclusion, the present study suggests that Fyn knockdown inhibits cell migration and invasion by regulating the AMPK/mTOR signaling pathway in CCA cell lines and that Fyn knockdown is a potential target for anti-CCA therapy.","Source":"STN","category":"ANIMAL","training_data":"Fyn Knockdown Inhibits Migration And Invasion In Cholangiocarcinoma Through The Activated Ampk/Mtor Signaling Pathway Cholangiocarcinoma (CCA) is a rare and fatal tumor. In previous decades, there has been a steady increase in the incidence and mortality rates of this tumor worldwide. Metastasis is regarded as the major factor that contributes to poor prognosis in CCA patients. Studies therefore aim to develop novel therapeutic targets to control CCA metastasis. Fyn is known to enhance expression and promote metastasis in various cancers, including pancreatic cancer, prostate cancer and colorectal cancer. However, the exact function and mechanism of Fyn in CCA metastasis remains unclear. In the present study, mRNA and protein expression levels of Fyn, AMP-activated protein kinase (AMPK), phosphorylated (p-)AMPK, mammalian target of rapamycin (mTOR) and p-mTOR were measured, using the reverse transcription-quantitative polymerase chain reaction and western blot analysis, in CCA tissues and cell lines. In addition, Transwell assays were used to determine the migratory and invasive abilities of human CCA QBC939, following transfection. In the present study, it was found that Fyn was overexpressed in CCA cell lines. Fyn knockdown inhibited CCA cell migration and invasion. Furthermore, it was demonstrated that Fyn knockdown induces phosphorylation of AMPK, inhibits downstream phosphorylation of mTOR, and activate the AMPK/mTOR signaling pathway. Compound C, an AMPK inhibitor, inhibited the AMPK/mTOR signaling pathway, and reversed the effect of Fyn knockdown on migration and invasion of CCA cells. In conclusion, the present study suggests that Fyn knockdown inhibits cell migration and invasion by regulating the AMPK/mTOR signaling pathway in CCA cell lines and that Fyn knockdown is a potential target for anti-CCA therapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"elevated plasma il 6 associates increased risk advanced fibrosis cholangiocarcinoma individuals infected opisthorchis viverrini opisthorchis viverrini considered among important food borne trematodes due strong association advanced periductal fibrosis bile duct cancer cholangiocarcinoma investigated relationship plasma levels interleukin il 6 risk developing advanced fibrosis bile duct cancer chronic opisthorchis infection show il 6 circulates plasma concentrations 58 times higher individuals advanced fibrosis age sex nearest neighbor matched controls 221 times higher individuals bile duct cancer controls also observed dose response relationship increasing levels plasma il 6 increasing risk advanced fibrosis bile duct cancer example age sex adjusted analyses individuals highest quartiles plasma il 6 19 times greater risk developing advanced periductal fibrosis 150 times greater risk developing bile duct cancer individuals detectable level plasma il 6 finally show single plasma il 6 measurement excellent positive predictive value detection advanced bile duct fibrosis bile duct cancer regions high o viverrini transmission data support hypothesis common mechanisms drive bile duct fibrosis bile duct tumorogenesis chronic o viverrini infection study also adds unique aspect literature circulating levels il 6 immune marker hepatobiliary pathology showing high levels circulating il 6 plasma related infection o viverrini development advanced often lethal pathologies resulting chronic o viverrini infection pubmed","probabilities":0.9799733,"Title":"Elevated plasma IL-6 associates with increased risk of advanced fibrosis and cholangiocarcinoma in individuals infected by Opisthorchis viverrini","Abstract":"Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and increasing risk of advanced fibrosis and bile duct cancer; for example, in age and sex adjusted analyses, individuals with the highest quartiles of plasma IL-6 had a 19 times greater risk of developing advanced periductal fibrosis and a 150 times greater risk of developing of bile duct cancer than individuals with no detectable level of plasma IL-6. Finally, we show that a single plasma IL-6 measurement has excellent positive predictive value for the detection of both advanced bile duct fibrosis and bile duct cancer in regions with high O. viverrini transmission. These data support our hypothesis that common mechanisms drive bile duct fibrosis and bile duct tumorogenesis from chronic O. viverrini infection. Our study also adds a unique aspect to the literature on circulating levels of IL-6 as an immune marker of hepatobiliary pathology by showing that high levels of circulating IL-6 in plasma are not related to infection with O. viverrini, but to the development of the advanced and often lethal pathologies resulting from chronic O. viverrini infection.","Source":"PubMed","category":"HUMAN","training_data":"Elevated plasma IL-6 associates with increased risk of advanced fibrosis and cholangiocarcinoma in individuals infected by Opisthorchis viverrini Opisthorchis viverrini is considered among the most important of the food-borne trematodes due to its strong association with advanced periductal fibrosis and bile duct cancer (cholangiocarcinoma). We investigated the relationship between plasma levels of Interleukin (IL)-6 and the risk of developing advanced fibrosis and bile duct cancer from chronic Opisthorchis infection. We show that IL-6 circulates in plasma at concentrations 58 times higher in individuals with advanced fibrosis than age, sex, and nearest-neighbor matched controls and 221 times higher in individuals with bile duct cancer than controls. We also observed a dose-response relationship between increasing levels of plasma IL-6 and increasing risk of advanced fibrosis and bile duct cancer; for example, in age and sex adjusted analyses, individuals with the highest quartiles of plasma IL-6 had a 19 times greater risk of developing advanced periductal fibrosis and a 150 times greater risk of developing of bile duct cancer than individuals with no detectable level of plasma IL-6. Finally, we show that a single plasma IL-6 measurement has excellent positive predictive value for the detection of both advanced bile duct fibrosis and bile duct cancer in regions with high O. viverrini transmission. These data support our hypothesis that common mechanisms drive bile duct fibrosis and bile duct tumorogenesis from chronic O. viverrini infection. Our study also adds a unique aspect to the literature on circulating levels of IL-6 as an immune marker of hepatobiliary pathology by showing that high levels of circulating IL-6 in plasma are not related to infection with O. viverrini, but to the development of the advanced and often lethal pathologies resulting from chronic O. viverrini infection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"stereotactic body radiotherapy sbrt locally advanced intrahepatic extrahepatic cholangiocarcinoma background evaluate role ablative radiotherapy doses treatment hilar intrahepatic cholangiocarcinoma ccc using stereotactic body radiotherapy sbrt methods consecutive patients treated 2007 2016 ccc evaluated local control toxicities assessed every 3 months according response evaluation criteria solid tumors recist common terminology criteria adverse events v4 0 respectively overall survival os local control lc progression free survival calculated sbrt results thirty seven patients 43 lesions retrospectively evaluated median dose delivered 45 gy range 25 66 gy 3 12 fractions corresponding median equivalent dose 2 gy fractions eqd2 10 56 range 25 85 gy median follow 24 months os 1 year 56 median os 14 95 ci 7 8 20 2 months start sbrt 22 95 ci 17 5 26 5 months diagnosis eight lesions progressed locally local control rate lc 1 year 78 median progression free survival 9 months 95 ci 2 8 15 2 21 patients progressed liver field 15 progressed distantly sbrt well tolerated three patients 9 developed grade iii bleeding seven patients developed cholangitis one due progression stent dysfunction 2 21 median 8 months sbrt conclusion patients locally advanced cholangiocarcinoma sbrt local treatment option acceptable toxicity profile warrants investigation prospective trials pubmed","probabilities":0.9799733,"Title":"Stereotactic body radiotherapy (SBRT) for locally advanced intrahepatic and extrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: To evaluate the role of ablative radiotherapy doses in the treatment of hilar or intrahepatic cholangiocarcinoma (CCC) using stereotactic body radiotherapy (SBRT). METHODS: Consecutive patients treated from 2007 to 2016 with CCC were evaluated. Local control and toxicities were assessed every 3 months according to the Response Evaluation Criteria In Solid Tumors (RECIST) and the Common Terminology Criteria for Adverse Events v4.0, respectively. Overall survival (OS), local control (LC) and progression free survival were calculated from SBRT. RESULTS: Thirty seven patients with 43 lesions were retrospectively evaluated. The median dose delivered was 45 Gy (range 25-66 Gy) in 3-12 fractions, corresponding to a median equivalent dose in 2 Gy fractions (EQD2(10)) of 56 (range 25-85) Gy. The median follow up was 24 months. The OS at 1 year was 56% with a median OS of 14 (95% CI: 7.8-20.2) months from start of SBRT and 22 (95% CI: 17.5-26.5) months from diagnosis. Eight lesions progressed locally. The local control rate (LC) at 1 year was 78%. The median progression free survival was 9 months (95% CI 2.8-15.2) 21 patients progressed in the liver but out of field and 15 progressed distantly. SBRT was well tolerated. Three patients (9%) developed a Grade III bleeding. Seven patients developed a cholangitis, one due to progression and the other because of a stent dysfunction 2-21(median 8) months from SBRT. CONCLUSION: In patients with locally advanced cholangiocarcinoma, SBRT is a local treatment option with an acceptable toxicity profile which warrants further investigation in prospective trials.","Source":"PubMed","category":"HUMAN","training_data":"Stereotactic body radiotherapy (SBRT) for locally advanced intrahepatic and extrahepatic cholangiocarcinoma BACKGROUND: To evaluate the role of ablative radiotherapy doses in the treatment of hilar or intrahepatic cholangiocarcinoma (CCC) using stereotactic body radiotherapy (SBRT). METHODS: Consecutive patients treated from 2007 to 2016 with CCC were evaluated. Local control and toxicities were assessed every 3 months according to the Response Evaluation Criteria In Solid Tumors (RECIST) and the Common Terminology Criteria for Adverse Events v4.0, respectively. Overall survival (OS), local control (LC) and progression free survival were calculated from SBRT. RESULTS: Thirty seven patients with 43 lesions were retrospectively evaluated. The median dose delivered was 45 Gy (range 25-66 Gy) in 3-12 fractions, corresponding to a median equivalent dose in 2 Gy fractions (EQD2(10)) of 56 (range 25-85) Gy. The median follow up was 24 months. The OS at 1 year was 56% with a median OS of 14 (95% CI: 7.8-20.2) months from start of SBRT and 22 (95% CI: 17.5-26.5) months from diagnosis. Eight lesions progressed locally. The local control rate (LC) at 1 year was 78%. The median progression free survival was 9 months (95% CI 2.8-15.2) 21 patients progressed in the liver but out of field and 15 progressed distantly. SBRT was well tolerated. Three patients (9%) developed a Grade III bleeding. Seven patients developed a cholangitis, one due to progression and the other because of a stent dysfunction 2-21(median 8) months from SBRT. CONCLUSION: In patients with locally advanced cholangiocarcinoma, SBRT is a local treatment option with an acceptable toxicity profile which warrants further investigation in prospective trials. PubMed","prediction_labels":"HUMAN"},{"cleaned":"loss bap1 expression associated genetic mutation predict outcomes gallbladder cancer background brca 1 associated protein bap1 de ubiquitinating enzyme regulates gene expression recently bap1 mutation involvement cancer survival reported range tumor types including uveal melanoma mesothelioma renal cancers biliary tract cancers however frequency bap1 mutation regulation varies among tumor types little known function bap1 silencing cancer cells gallbladder carcinoma gbc type biliary tract cancer poor prognosis mutational studies investigated role bap1 gbc functional study vitro clinical studies cancer survival done methods gbc cells studied following small interfering rna mediated silencing bap1 regard proliferation migration invasion drug sensitivity carried genomic epigenomic immunohistochemical analyses detect somatic bap1 alterations 47 gbc patients undergoing surgical resection results bap1 depletion resulted increased migration invasion proliferation also resulted decreased sensitivity bortezomib proteasome inhibitor suppressed expression bap1 occurred 22 gbc cases 46 8 showed strong trend toward worse median survival time 13 3 months 95 ci 17 6 62 6 p 0 0034 sanger sequencing revealed loss function mutation bap1 11 22 gbc cases 50 low bap1 expression whereas 2 25 gbc cases 8 detected cases high bap1 expression partial changes methylation observed 6 47 cases methylation show strong relationship bap1 expression prognosis conclusion findings showed genetic mutations involved bap1 regulation leading promotion invasive character cancer cells poor prognosis gbc stn","probabilities":0.9799733,"Title":"Loss Of Bap1 Expression Is Associated With Genetic Mutation And Can Predict Outcomes In Gallbladder Cancer","Abstract":"Background: BRCA-1 associated protein (BAP1) is a de-ubiquitinating enzyme that regulates gene expression. Recently, the BAP1 mutation and its involvement in cancer survival have been reported in a range of tumor types, including uveal melanoma, mesothelioma, renal cancers, and biliary tract cancers. However, the frequency of BAP1 mutation and down-regulation varies among tumor types, and little is known about the function of BAP1 silencing in cancer cells. Gallbladder carcinoma (GBC) is a type of biliary tract cancer with a poor prognosis. Few mutational studies have investigated the role of BAP1 in GBC, and no functional study in vitro-, or clinical studies about cancer survival have been done. \r\n\r\n Methods: GBC cells were studied by following the small interfering RNA mediated silencing of BAP1 with regard to proliferation, migration, invasion, and drug sensitivity. We carried out genomic, epigenomic and immunohistochemical analyses to detect somatic BAP1 alterations in 47 GBC patients undergoing surgical resection. \r\n\r\n Results: BAP1 depletion resulted in increased migration and invasion, but not proliferation, and also resulted in decreased sensitivity to bortezomib, a proteasome inhibitor. Suppressed expression of BAP1 occurred in 22 GBC cases (46.8%) and showed a strong trend toward a worse median survival time of 13.3 months (95% CI, 17.6-62.6) (p = 0.0034). Sanger sequencing revealed a loss-of-function mutation of BAP1 in 11 out of these 22 GBC cases (50%) with low BAP1 expression, whereas 2 out of 25 GBC cases (8%) were detected in cases with high BAP1 expression. Partial changes in methylation were observed in 6 out of 47 cases, but methylation did not show a strong relationship to BAP1 expression or to the prognosis. \r\n\r\n Conclusion: Our findings showed that genetic mutations are involved in BAP1 down-regulation, leading to promotion of the invasive character of cancer cells and poor prognosis in GBC.","Source":"STN","category":"ANIMAL","training_data":"Loss Of Bap1 Expression Is Associated With Genetic Mutation And Can Predict Outcomes In Gallbladder Cancer Background: BRCA-1 associated protein (BAP1) is a de-ubiquitinating enzyme that regulates gene expression. Recently, the BAP1 mutation and its involvement in cancer survival have been reported in a range of tumor types, including uveal melanoma, mesothelioma, renal cancers, and biliary tract cancers. However, the frequency of BAP1 mutation and down-regulation varies among tumor types, and little is known about the function of BAP1 silencing in cancer cells. Gallbladder carcinoma (GBC) is a type of biliary tract cancer with a poor prognosis. Few mutational studies have investigated the role of BAP1 in GBC, and no functional study in vitro-, or clinical studies about cancer survival have been done. \r\n\r\n Methods: GBC cells were studied by following the small interfering RNA mediated silencing of BAP1 with regard to proliferation, migration, invasion, and drug sensitivity. We carried out genomic, epigenomic and immunohistochemical analyses to detect somatic BAP1 alterations in 47 GBC patients undergoing surgical resection. \r\n\r\n Results: BAP1 depletion resulted in increased migration and invasion, but not proliferation, and also resulted in decreased sensitivity to bortezomib, a proteasome inhibitor. Suppressed expression of BAP1 occurred in 22 GBC cases (46.8%) and showed a strong trend toward a worse median survival time of 13.3 months (95% CI, 17.6-62.6) (p = 0.0034). Sanger sequencing revealed a loss-of-function mutation of BAP1 in 11 out of these 22 GBC cases (50%) with low BAP1 expression, whereas 2 out of 25 GBC cases (8%) were detected in cases with high BAP1 expression. Partial changes in methylation were observed in 6 out of 47 cases, but methylation did not show a strong relationship to BAP1 expression or to the prognosis. \r\n\r\n Conclusion: Our findings showed that genetic mutations are involved in BAP1 down-regulation, leading to promotion of the invasive character of cancer cells and poor prognosis in GBC. STN","prediction_labels":"HUMAN"},{"cleaned":"activation mammalian target rapamycin complex 1 mtorc1 raf pyk2 growth factor mediated eph receptor 2 epha2 required cholangiocarcinoma growth metastasis eph receptor 2 epha2 overexpression frequently accompanied loss cognate ligand tumor progression however molecular mechanism ligand independent promotion tumor epha2 remains unclear highly malignant fatal cholangiocarcinoma cc examined biological role epha2 tumor growth metastasis cc tissues cells according degree differentiation explored downstream signaling pathways epha2 growth factor mediated epha2 overexpression leads activation mammalian target rapamycin complex 1 mtorc1 extracellular signal regulated kinase erk pathways ligand independent activation epha2 phosphorylation s897 vitro soft agar assay vivo orthotopic subcutaneous tumor model showed epha2 enhanced colony formation accelerated tumor growth seemed mainly associated akt t308 mtorc1 activation aberrant expression activation epha2 also associated poorer differentiation higher metastatic ability enhanced metastatic ability also observed orthotopic tumor model lung metastasis model correlating pyk2 y402 c src erk activation addition activation canonical raf mek erk pathway mtorc1 raf pyk2 pathways also appeared affect results suggest growth factor mediated epha2 might involved tumor growth metastasis activation mtorc1 raf pyk2 pathways therapeutic strategies target epha2 downstream effectors may useful control cc hepatology 2013 57 2248 2260 stn","probabilities":0.88235295,"Title":"Activation Of Mammalian Target Of Rapamycin Complex 1 (Mtorc1) And Raf/Pyk2 By Growth Factor-Mediated Eph Receptor 2 (Epha2) Is Required For Cholangiocarcinoma Growth And Metastasis","Abstract":"Eph receptor 2 (EphA2) overexpression is frequently accompanied by the loss of its cognate ligand during tumor progression. However, the molecular mechanism of this ligand-independent promotion of tumor by EphA2 remains unclear in highly malignant and fatal cholangiocarcinoma (CC). We examined the biological role of EphA2 in tumor growth and metastasis in CC tissues and cells according to the degree of differentiation and we explored the downstream signaling pathways of EphA2. Growth factor-mediated EphA2 overexpression itself leads to the activation of the mammalian target of rapamycin complex 1 (mTORC1) and extracellular signal-regulated kinase (ERK) pathways through ligand-independent activation of EphA2 (phosphorylation of S897). An in vitro soft agar assay and in vivo orthotopic or subcutaneous tumor model showed that EphA2 enhanced colony formation and accelerated tumor growth, and which seemed to be mainly associated with Akt (T308)/mTORC1 activation. Aberrant expression and activation of EphA2 was also associated with poorer differentiation and higher metastatic ability. Enhanced metastatic ability was also observed in an orthotopic tumor model or lung metastasis model, correlating with Pyk2(Y402)/c-Src/ERK activation in addition to activation of the canonical Raf/MEK/ERK pathway. The mTORC1 and Raf/Pyk2 pathways also appeared to affect each other. These results suggest that growth factor-mediated EphA2 might be involved in tumor growth and metastasis through activation of the mTORC1 and Raf/Pyk2 pathways. Therapeutic strategies that target EphA2 and its downstream effectors may be useful to control CC. (HEPATOLOGY 2013;57:2248-2260).","Source":"STN","category":"ANIMAL","training_data":"Activation Of Mammalian Target Of Rapamycin Complex 1 (Mtorc1) And Raf/Pyk2 By Growth Factor-Mediated Eph Receptor 2 (Epha2) Is Required For Cholangiocarcinoma Growth And Metastasis Eph receptor 2 (EphA2) overexpression is frequently accompanied by the loss of its cognate ligand during tumor progression. However, the molecular mechanism of this ligand-independent promotion of tumor by EphA2 remains unclear in highly malignant and fatal cholangiocarcinoma (CC). We examined the biological role of EphA2 in tumor growth and metastasis in CC tissues and cells according to the degree of differentiation and we explored the downstream signaling pathways of EphA2. Growth factor-mediated EphA2 overexpression itself leads to the activation of the mammalian target of rapamycin complex 1 (mTORC1) and extracellular signal-regulated kinase (ERK) pathways through ligand-independent activation of EphA2 (phosphorylation of S897). An in vitro soft agar assay and in vivo orthotopic or subcutaneous tumor model showed that EphA2 enhanced colony formation and accelerated tumor growth, and which seemed to be mainly associated with Akt (T308)/mTORC1 activation. Aberrant expression and activation of EphA2 was also associated with poorer differentiation and higher metastatic ability. Enhanced metastatic ability was also observed in an orthotopic tumor model or lung metastasis model, correlating with Pyk2(Y402)/c-Src/ERK activation in addition to activation of the canonical Raf/MEK/ERK pathway. The mTORC1 and Raf/Pyk2 pathways also appeared to affect each other. These results suggest that growth factor-mediated EphA2 might be involved in tumor growth and metastasis through activation of the mTORC1 and Raf/Pyk2 pathways. Therapeutic strategies that target EphA2 and its downstream effectors may be useful to control CC. (HEPATOLOGY 2013;57:2248-2260). STN","prediction_labels":"HUMAN"},{"cleaned":"liver directed therapy hepatic metastases patients undergoing pancreaticoduodenectomy dual center analysis objectives analyze perioperative long term outcomes patients undergoing liver directed therapy pancreaticoduodenectomy large dual center cohort patients background although aggressive liver directed therapy may beneficial liver directed therapy may associated high risk complications pancreaticoduodenectomy methods 5025 patients underwent pancreaticoduodenectomy johns hopkins hospital mayo clinic 1970 2008 126 2 5 patients identified also treated either simultaneous staged liver directed therapy data demographics primary tumor hepatic metastasis characteristics well details liver directed therapy collected analyzed results primary tumor histology included neuroendocrine carcinoma 34 9 pancreatic ductal adenocarcinoma 33 4 distal cholangiocarcinoma 8 7 ampullary carcinoma 7 1 duodenal carcinoma 4 0 11 9 liver directed therapies included hepatic resection alone 45 2 hepatic resection plus ablation 11 1 ablation alone 7 9 transarterial chemoembolization 9 5 whole liver irradiation 22 2 overall morbidity following liver directed therapy 34 1 overall mortality 2 4 patients undergoing staged liver directed therapy 14 5 versus simultaneous pancreaticoduodenectomy plus liver directed therapy 7 0 likely develop liver abscess p 0 05 patients developed complications majority 55 8 major clavien grade 3 conclusions pancreaticoduodenectomy plus liver directed therapy associated considerable morbidity incidence hepatic abscess increased patients undergoing staged pancreaticoduodenectomy followed liver directed therapy pubmed","probabilities":0.9799733,"Title":"Liver-directed therapy for hepatic metastases in patients undergoing pancreaticoduodenectomy: a dual-center analysis","Abstract":"OBJECTIVES: To analyze the perioperative and long-term outcomes of patients undergoing liver-directed therapy after pancreaticoduodenectomy in a large dual-center cohort of patients. BACKGROUND: Although aggressive liver-directed therapy may be beneficial, liver-directed therapy may be associated with a high risk of complications after pancreaticoduodenectomy. METHODS: Of 5025 patients who underwent pancreaticoduodenectomy at the Johns Hopkins Hospital and the Mayo Clinic between 1970 and 2008, 126 (2.5%), patients were identified who were also treated with either simultaneous or staged liver-directed therapy. Data on demographics, primary tumor, and hepatic metastasis characteristics, as well as details of the liver-directed therapy were collected and analyzed. RESULTS: Primary tumor histology included neuroendocrine carcinoma (34.9%), pancreatic ductal adenocarcinoma (33.4%), distal cholangiocarcinoma (8.7%), ampullary carcinoma (7.1%), duodenal carcinoma (4.0%), or other (11.9%). Liver-directed therapies included hepatic resection alone (45.2%), hepatic resection plus ablation (11.1%), ablation alone (7.9%), transarterial chemoembolization (9.5%), and whole-liver irradiation (22.2%). The overall morbidity following liver-directed therapy was 34.1% and overall mortality was 2.4%. Patients undergoing staged liver-directed therapy (14.5%) versus simultaneous pancreaticoduodenectomy plus liver-directed therapy (7.0%) were more likely to develop a liver abscess (P < 0.05). Of those patients who developed complications, the majority (55.8%) were major (Clavien grade >or=3). CONCLUSIONS: Pancreaticoduodenectomy plus liver-directed therapy is associated with considerable morbidity. The incidence of hepatic abscess is increased in patients undergoing staged pancreaticoduodenectomy followed by liver-directed therapy.","Source":"PubMed","category":"HUMAN","training_data":"Liver-directed therapy for hepatic metastases in patients undergoing pancreaticoduodenectomy: a dual-center analysis OBJECTIVES: To analyze the perioperative and long-term outcomes of patients undergoing liver-directed therapy after pancreaticoduodenectomy in a large dual-center cohort of patients. BACKGROUND: Although aggressive liver-directed therapy may be beneficial, liver-directed therapy may be associated with a high risk of complications after pancreaticoduodenectomy. METHODS: Of 5025 patients who underwent pancreaticoduodenectomy at the Johns Hopkins Hospital and the Mayo Clinic between 1970 and 2008, 126 (2.5%), patients were identified who were also treated with either simultaneous or staged liver-directed therapy. Data on demographics, primary tumor, and hepatic metastasis characteristics, as well as details of the liver-directed therapy were collected and analyzed. RESULTS: Primary tumor histology included neuroendocrine carcinoma (34.9%), pancreatic ductal adenocarcinoma (33.4%), distal cholangiocarcinoma (8.7%), ampullary carcinoma (7.1%), duodenal carcinoma (4.0%), or other (11.9%). Liver-directed therapies included hepatic resection alone (45.2%), hepatic resection plus ablation (11.1%), ablation alone (7.9%), transarterial chemoembolization (9.5%), and whole-liver irradiation (22.2%). The overall morbidity following liver-directed therapy was 34.1% and overall mortality was 2.4%. Patients undergoing staged liver-directed therapy (14.5%) versus simultaneous pancreaticoduodenectomy plus liver-directed therapy (7.0%) were more likely to develop a liver abscess (P < 0.05). Of those patients who developed complications, the majority (55.8%) were major (Clavien grade >or=3). CONCLUSIONS: Pancreaticoduodenectomy plus liver-directed therapy is associated with considerable morbidity. The incidence of hepatic abscess is increased in patients undergoing staged pancreaticoduodenectomy followed by liver-directed therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role dna repair glycosylase ogg1 intrahepatic cholangiocarcinoma background aim effects oxidative stress various carcinomas reported previous studies intrahepatic cholangiocarcinoma icc fully elucidated purpose study thus reveal effects oxidative dna damage repair enzymes icc materials methods levels 8 hydroxydeoxyguanosine 8 ohdg 8 ohdg dna glycosylase ogg1 immunohistochemically evaluated specimens resected 63 patients icc results low ogg1 expression related tumour depth t4 p 0 04 venous invasion p 0 0005 lymphatic vessel invasion p 0 03 perineural invasion p 0 03 compared high ogg1 expression group patients low ogg1 expression significantly poorer prognosis overall survival p 0 04 recurrence free survival p 0 02 unlike ogg1 expression levels 8 ohdg showed association prognosis conclusion oxidative dna damage dna repair enzymes may closely related icc progression pubmed","probabilities":0.9799733,"Title":"The Role of DNA Repair Glycosylase OGG1 in Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND/AIM: The effects of oxidative stress on various carcinomas were reported in previous studies, but those in intrahepatic cholangiocarcinoma (ICC) have not been fully elucidated. The purpose of this study was, thus, to reveal the effects of oxidative DNA damage and repair enzymes on ICC. MATERIALS AND METHODS: The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-OHdG DNA glycosylase (OGG1) were immunohistochemically evaluated in specimens resected from 63 patients with ICC. RESULTS: Low OGG1 expression was related to tumour depth T4 (p=0.04), venous invasion (p=0.0005), lymphatic vessel invasion (p=0.03), and perineural invasion (p=0.03). Compared to the high-OGG1-expression group, patients with low OGG1 expression had a significantly poorer prognosis (overall survival: p=0.04, recurrence-free survival: p=0.02). Unlike for OGG1, the expression levels of 8-OHdG showed no association with prognosis. CONCLUSION: Oxidative DNA damage and DNA repair enzymes may be closely related to ICC progression.","Source":"PubMed","category":"HUMAN","training_data":"The Role of DNA Repair Glycosylase OGG1 in Intrahepatic Cholangiocarcinoma BACKGROUND/AIM: The effects of oxidative stress on various carcinomas were reported in previous studies, but those in intrahepatic cholangiocarcinoma (ICC) have not been fully elucidated. The purpose of this study was, thus, to reveal the effects of oxidative DNA damage and repair enzymes on ICC. MATERIALS AND METHODS: The levels of 8-hydroxydeoxyguanosine (8-OHdG) and 8-OHdG DNA glycosylase (OGG1) were immunohistochemically evaluated in specimens resected from 63 patients with ICC. RESULTS: Low OGG1 expression was related to tumour depth T4 (p=0.04), venous invasion (p=0.0005), lymphatic vessel invasion (p=0.03), and perineural invasion (p=0.03). Compared to the high-OGG1-expression group, patients with low OGG1 expression had a significantly poorer prognosis (overall survival: p=0.04, recurrence-free survival: p=0.02). Unlike for OGG1, the expression levels of 8-OHdG showed no association with prognosis. CONCLUSION: Oxidative DNA damage and DNA repair enzymes may be closely related to ICC progression. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder cancer laparoscopic cholecystectomy managing unexpected finding aim evaluate impact incidental gallbladder cancer surgical experience methods 1998 2008 cases cholecystectomy two divisions general surgery one university based one public hospital retrospectively reviewed gallbladder pathology diagnosed history physical examination laboratory imaging studies ultrasonography computed tomography ct patients gallbladder cancer gbc analyzed demographic data type operation surgical morbidity mortality histopathological classification survival incidental gbc compared suspected preoperatively diagnosed gbc primary endpoint disease free survival dfs secondary endpoint difference dfs patients previously treated laparoscopic cholecystectomy oncological resection first intervention results nineteen patients 11 women eight men found gbc male female ratio 1 1 4 mean age 68 years range 45 82 years preoperative diagnosis made 10 cases eight diagnosed postoperatively one suspected intraoperatively confirmed frozen sections ratio incidental nonincidental cases 9 19 tumor node metastasis stage ptis 1 pt1a 2 pt1b 4 pt2 6 pt3 4 pt4 2 five cases stage ia t1 b two stage ib t2 n0 one stage iia t3 n0 six stage iib t1 t3 n1 two stage iii t4 nx nx one stage iv tx nx mx eighty eight percent incidental cases discovered early stage ii preoperative diagnosis 19 patients gbc gbc liver invasion diagnosed preoperative ct nine cases gallbladder abscess perforated hepatic parenchyma involving transversal mesocolon hepatic hilum one case porcelain gallbladder one case gallbladder adenoma one case chronic cholelithiasis eight cases every case except one t1b advanced invasion underwent ivb v wedge liver resection pericholedochic hepatoduodenal lymphadenectomy one patient stage t1b gbc refused surgery cases tis t1a involvement treated cholecystectomy alone one incidental case diagnosed intraoperative frozen section treated cholecystectomy alone six nine patients incidental diagnosis reached 5 year dfs one patient reached 38 mo survival despite port site recurrence 2 years original surgery cases non incidental diagnosis locally advanced two patients experienced 5 year dfs conclusion laparoscopic cholecystectomy affect survival implemented properly reoperation two objectives r0 resection clearance lymph nodes stn","probabilities":0.9799733,"Title":"Incidental Gallbladder Cancer During Laparoscopic Cholecystectomy: Managing An Unexpected Finding","Abstract":"Aim: To evaluate the impact of incidental gallbladder cancer on surgical experience. \r\n\r\n Methods: Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery, one university based and one at a public hospital, were retrospectively reviewed. Gallbladder pathology was diagnosed by history, physical examination, and laboratory and imaging studies [ultrasonography and computed tomography (CT)]. Patients with gallbladder cancer (GBC) were further analyzed for demographic data, and type of operation, surgical morbidity and mortality, histopathological classification, and survival. Incidental GBC was compared with suspected or preoperatively diagnosed GBC. The primary endpoint was disease-free survival (DFS). The secondary endpoint was the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention. \r\n\r\n Results: Nineteen patients (11 women and eight men) were found to have GBC. The male to female ratio was 1:1.4 and the mean age was 68 years (range: 45-82 years). Preoperative diagnosis was made in 10 cases, and eight were diagnosed postoperatively. One was suspected intraoperatively and confirmed by frozen sections. The ratio between incidental and nonincidental cases was 9/19. The tumor node metastasis stage was: pTis (1), pT1a (2), pT1b (4), pT2 (6), pT3 (4), pT4 (2); five cases with stage Ia (T1 a-b); two with stage Ib (T2 N0); one with stage IIa (T3 N0); six with stage IIb (T1-T3 N1); two with stage III (T4 Nx Nx); and one with stage IV (Tx Nx Mx). Eighty-eight percent of the incidental cases were discovered at an early stage (≤ II). Preoperative diagnosis of the 19 patients with GBC was: GBC with liver invasion diagnosed by preoperative CT (nine cases), gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum (one case), porcelain gallbladder (one case), gallbladder adenoma (one case), and chronic cholelithiasis (eight cases). Every case, except one, with a T1b or more advanced invasion underwent IVb + V wedge liver resection and pericholedochic/hepatoduodenal lymphadenectomy. One patient with stage T1b GBC refused further surgery. Cases with Tis and T1a involvement were treated with cholecystectomy alone. One incidental case was diagnosed by intraoperative frozen section and treated with cholecystectomy alone. Six of the nine patients with incidental diagnosis reached 5-year DFS. One patient reached 38 mo survival despite a port-site recurrence 2 years after original surgery. Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5-year DFS. \r\n\r\n Conclusion: Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes.","Source":"STN","category":"HUMAN","training_data":"Incidental Gallbladder Cancer During Laparoscopic Cholecystectomy: Managing An Unexpected Finding Aim: To evaluate the impact of incidental gallbladder cancer on surgical experience. \r\n\r\n Methods: Between 1998 and 2008 all cases of cholecystectomy at two divisions of general surgery, one university based and one at a public hospital, were retrospectively reviewed. Gallbladder pathology was diagnosed by history, physical examination, and laboratory and imaging studies [ultrasonography and computed tomography (CT)]. Patients with gallbladder cancer (GBC) were further analyzed for demographic data, and type of operation, surgical morbidity and mortality, histopathological classification, and survival. Incidental GBC was compared with suspected or preoperatively diagnosed GBC. The primary endpoint was disease-free survival (DFS). The secondary endpoint was the difference in DFS between patients previously treated with laparoscopic cholecystectomy and those who had oncological resection as first intervention. \r\n\r\n Results: Nineteen patients (11 women and eight men) were found to have GBC. The male to female ratio was 1:1.4 and the mean age was 68 years (range: 45-82 years). Preoperative diagnosis was made in 10 cases, and eight were diagnosed postoperatively. One was suspected intraoperatively and confirmed by frozen sections. The ratio between incidental and nonincidental cases was 9/19. The tumor node metastasis stage was: pTis (1), pT1a (2), pT1b (4), pT2 (6), pT3 (4), pT4 (2); five cases with stage Ia (T1 a-b); two with stage Ib (T2 N0); one with stage IIa (T3 N0); six with stage IIb (T1-T3 N1); two with stage III (T4 Nx Nx); and one with stage IV (Tx Nx Mx). Eighty-eight percent of the incidental cases were discovered at an early stage (≤ II). Preoperative diagnosis of the 19 patients with GBC was: GBC with liver invasion diagnosed by preoperative CT (nine cases), gallbladder abscess perforated into hepatic parenchyma and involving the transversal mesocolon and hepatic hilum (one case), porcelain gallbladder (one case), gallbladder adenoma (one case), and chronic cholelithiasis (eight cases). Every case, except one, with a T1b or more advanced invasion underwent IVb + V wedge liver resection and pericholedochic/hepatoduodenal lymphadenectomy. One patient with stage T1b GBC refused further surgery. Cases with Tis and T1a involvement were treated with cholecystectomy alone. One incidental case was diagnosed by intraoperative frozen section and treated with cholecystectomy alone. Six of the nine patients with incidental diagnosis reached 5-year DFS. One patient reached 38 mo survival despite a port-site recurrence 2 years after original surgery. Cases with non incidental diagnosis were more locally advanced and only two patients experienced 5-year DFS. \r\n\r\n Conclusion: Laparoscopic cholecystectomy does not affect survival if implemented properly. Reoperation should have two objectives: R0 resection and clearance of the lymph nodes. STN","prediction_labels":"HUMAN"},{"cleaned":"ck20 lymph node involvement predict adverse outcome malignant intraductal papillary neoplasm bile duct objectives identify prognostic factors malignant intraductal papillary neoplasm bile duct m ipnb materials methods included 38 consecutive cases underwent surgical resection diagnosed ipnb malignant component january 2003 january 2017 clinicopathological variables collected conduct survival analysis identify prognostic factors results median os m ipnb 76 0 months 1 3 5 year survival rates 97 2 73 5 59 8 respectively median rfs 48 0 months 1 3 5 year rfs rate 83 2 59 8 44 6 respectively univariate analysis showed elevation cea lymph node involvement resection margin status degree periductal invasion positive expression ck20 associated os rfs m ipnb multivariate cox models analysis lymph node involvement positive expression ck20 identified independent prognostic factors os lymph node involvement resection margin status independent prognostic factors rfs median os patients m ipnb involving lymphatic metastases positive expression ck20 27 0 8 8 months 51 0 12 4 months respectively median rfs cases lymph node involvement r1 resection 10 0 3 3 months 25 0 6 9 months respectively however significant difference os rfs cases pancreaticobiliary intestinal subtype conclusions lymph node involvement positive expression ck20 independent prognostic factors shorter os m ipnb patients lymph node involvement positive resection margin higher risk tumor recurrence stn","probabilities":0.9799733,"Title":"Ck20 And Lymph Node Involvement Predict Adverse Outcome Of Malignant Intraductal Papillary Neoplasm Of The Bile Duct","Abstract":"Objectives: To identify prognostic factors of malignant intraductal papillary neoplasm of the bile duct (m-IPNB). \r\n\r\n Materials and methods: We included 38 consecutive cases which underwent surgical resection and diagnosed as IPNB with malignant component from January 2003 to January 2017. Clinicopathological variables were collected to conduct survival analysis and identify prognostic factors. \r\n\r\n Results: The median OS of m-IPNB was 76.0 months, with 1-, 3-, and 5-year survival rates of 97.2%, 73.5%, and 59.8%, respectively. The median RFS was 48.0 months with 1-, 3-, and 5-year RFS rate was 83.2%, 59.8%, and 44.6%, respectively. Univariate analysis showed that elevation of CEA, lymph node involvement, resection margin status, degree of periductal invasion, and positive expression of CK20 were associated with both OS and RFS of m-IPNB. After multivariate Cox models analysis, lymph node involvement and positive expression of CK20 were identified as independent prognostic factors for OS, while lymph node involvement and resection margin status were independent prognostic factors for RFS. The median OS of patients with m-IPNB involving lymphatic metastases and positive expression of CK20 was 27.0±8.8 months and 51.0±12.4 months, respectively. The median RFS of cases with lymph node involvement and R1 resection was 10.0±3.3 months and 25.0±6.9 months, respectively. However, there was no significant difference in OS or RFS between cases of pancreaticobiliary and intestinal subtype. \r\n\r\n Conclusions: Lymph node involvement and positive expression of CK20 are independent prognostic factors for shorter OS of m-IPNB, while patients with lymph node involvement and positive resection margin are at higher risk of tumor recurrence.","Source":"STN","category":"HUMAN","training_data":"Ck20 And Lymph Node Involvement Predict Adverse Outcome Of Malignant Intraductal Papillary Neoplasm Of The Bile Duct Objectives: To identify prognostic factors of malignant intraductal papillary neoplasm of the bile duct (m-IPNB). \r\n\r\n Materials and methods: We included 38 consecutive cases which underwent surgical resection and diagnosed as IPNB with malignant component from January 2003 to January 2017. Clinicopathological variables were collected to conduct survival analysis and identify prognostic factors. \r\n\r\n Results: The median OS of m-IPNB was 76.0 months, with 1-, 3-, and 5-year survival rates of 97.2%, 73.5%, and 59.8%, respectively. The median RFS was 48.0 months with 1-, 3-, and 5-year RFS rate was 83.2%, 59.8%, and 44.6%, respectively. Univariate analysis showed that elevation of CEA, lymph node involvement, resection margin status, degree of periductal invasion, and positive expression of CK20 were associated with both OS and RFS of m-IPNB. After multivariate Cox models analysis, lymph node involvement and positive expression of CK20 were identified as independent prognostic factors for OS, while lymph node involvement and resection margin status were independent prognostic factors for RFS. The median OS of patients with m-IPNB involving lymphatic metastases and positive expression of CK20 was 27.0±8.8 months and 51.0±12.4 months, respectively. The median RFS of cases with lymph node involvement and R1 resection was 10.0±3.3 months and 25.0±6.9 months, respectively. However, there was no significant difference in OS or RFS between cases of pancreaticobiliary and intestinal subtype. \r\n\r\n Conclusions: Lymph node involvement and positive expression of CK20 are independent prognostic factors for shorter OS of m-IPNB, while patients with lymph node involvement and positive resection margin are at higher risk of tumor recurrence. STN","prediction_labels":"HUMAN"},{"cleaned":"confinement intrapancreatic bile duct independently associated better prognosis extrahepatic cholangiocarcinoma background actual differences long term outcome extrahepatic cholangiocarcinoma according location tumor yet studied aim study evaluate prognosis optimal surgical procedure middle bd cancer methods among 109 patients carcinoma extrahepatic bd underwent surgical resection curative resection extrahepatic bd cancer performed 90 patients classified three groups according location tumors distal n 32 tumor confined intrapancreatic bile duct mid n 20 tumor located confluence hepatic duct bifurcation suprapancreatic portion bd diffuse n 38 tumor located diffusely results tumor involving middle bd mid diffuse higher rate perineural invasion compared distal group overall disease free survival rate mid diffuse group significantly worse distal mid diffuse group significant difference survival according type operation pancreaticoduodenectomy segmental bd resection multivariate analysis showed tumor involving middle bd mid diffuse group node metastasis independently poor prognostic factors disease free overall survival conclusion extrahepatic cholangiocarcinoma involving extrapancreatic bd worse prognosis confined intrapancreatic bd patients tumors confined middle bd bd resection considered alternative surgical procedure pancreaticoduodenectomy r0 resection accomplished pubmed","probabilities":0.9799733,"Title":"Confinement to the intrapancreatic bile duct is independently associated with a better prognosis in extrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Actual differences of long term outcome of extrahepatic cholangiocarcinoma according to the location of the tumor have not yet been studied. The aim of this study was to evaluate the prognosis and optimal surgical procedure for middle (BD) cancer. METHODS: Among 109 patients with carcinoma of the extrahepatic BD underwent surgical resection, curative resection of extrahepatic BD cancer was performed in 90 patients. They were classified into three groups according to the location of tumors: DISTAL (n = 32), tumor was confined to the intrapancreatic bile duct; MID (n = 20), tumor was located between below the confluence of the hepatic duct bifurcation and suprapancreatic portion of the BD; and DIFFUSE (n = 38), tumor was located diffusely. RESULTS: Tumor involving the middle BD (MID or DIFFUSE) had a higher rate of perineural invasion as compared to the DISTAL group. The overall and disease-free survival rate for the MID or DIFFUSE group was significantly worse than that of DISTAL. In the MID/DIFFUSE group, there was no significant difference of survival according to the type of the operation (pancreaticoduodenectomy or segmental BD resection). The multivariate analysis showed that tumor involving middle BD (MID or DIFFUSE group) and node metastasis were independently poor prognostic factors for the disease free and overall survival. CONCLUSION: Extrahepatic cholangiocarcinoma involving the extrapancreatic BD has a worse prognosis than those confined to the intrapancreatic BD. In patients with tumors confined to the middle BD, BD resection can be considered as an alternative surgical procedure to pancreaticoduodenectomy, if an R0 resection can be accomplished.","Source":"PubMed","category":"HUMAN","training_data":"Confinement to the intrapancreatic bile duct is independently associated with a better prognosis in extrahepatic cholangiocarcinoma BACKGROUND: Actual differences of long term outcome of extrahepatic cholangiocarcinoma according to the location of the tumor have not yet been studied. The aim of this study was to evaluate the prognosis and optimal surgical procedure for middle (BD) cancer. METHODS: Among 109 patients with carcinoma of the extrahepatic BD underwent surgical resection, curative resection of extrahepatic BD cancer was performed in 90 patients. They were classified into three groups according to the location of tumors: DISTAL (n = 32), tumor was confined to the intrapancreatic bile duct; MID (n = 20), tumor was located between below the confluence of the hepatic duct bifurcation and suprapancreatic portion of the BD; and DIFFUSE (n = 38), tumor was located diffusely. RESULTS: Tumor involving the middle BD (MID or DIFFUSE) had a higher rate of perineural invasion as compared to the DISTAL group. The overall and disease-free survival rate for the MID or DIFFUSE group was significantly worse than that of DISTAL. In the MID/DIFFUSE group, there was no significant difference of survival according to the type of the operation (pancreaticoduodenectomy or segmental BD resection). The multivariate analysis showed that tumor involving middle BD (MID or DIFFUSE group) and node metastasis were independently poor prognostic factors for the disease free and overall survival. CONCLUSION: Extrahepatic cholangiocarcinoma involving the extrapancreatic BD has a worse prognosis than those confined to the intrapancreatic BD. In patients with tumors confined to the middle BD, BD resection can be considered as an alternative surgical procedure to pancreaticoduodenectomy, if an R0 resection can be accomplished. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hispanic ethnicity associated increased odds cholangiocarcinoma results nationwide analysis abstract available google scholar","probabilities":0.9799733,"Title":"Hispanic Ethnicity Associated With Increased Odds Of Cholangiocarcinoma: Results Of A Nationwide Analysis","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Hispanic Ethnicity Associated With Increased Odds Of Cholangiocarcinoma: Results Of A Nationwide Analysis Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"novel target genes valid biomarker panel identified cholangiocarcinoma cholangiocarcinoma notoriously difficult diagnose mortality rate high due late clinical presentation cpg island promoter methylation frequently seen cancer development present study aimed identifying novel epigenetic biomarkers potential improve diagnostic accuracy cholangiocarcinoma microarray data analyses cholangiocarcinoma cell lines treated epigenetic drugs untreated counterparts compared previously published gene expression profiles primary tumors non malignant controls genes responding epigenetic treatment simultaneously downregulated primary cholangiocarcinoma compared controls n 43 investigated promoter methylation status cancer cell lines gastrointestinal tract genes commonly methylated cholangiocarcinoma cell lines subjected quantitative methylation specific polymerase chain reaction total 93 clinical samples cholangiocarcinomas non malignant controls cdo1 dclk1 sfrp1 zscan18 displayed high methylation frequencies primary tumors unmethylated controls least one four biomarkers positive 87 tumor samples specificity 100 conclusion novel methylation based biomarker panel showed high sensitivity specificity cholangiocarcinoma potential markers early diagnosis cancer type explored pubmed","probabilities":0.875,"Title":"Novel target genes and a valid biomarker panel identified for cholangiocarcinoma","Abstract":"Cholangiocarcinoma is notoriously difficult to diagnose, and the mortality rate is high due to late clinical presentation. CpG island promoter methylation is frequently seen in cancer development. In the present study, we aimed at identifying novel epigenetic biomarkers with the potential to improve the diagnostic accuracy of cholangiocarcinoma. Microarray data analyses of cholangiocarcinoma cell lines treated with epigenetic drugs and their untreated counterparts were compared with previously published gene expression profiles of primary tumors and with non-malignant controls. Genes responding to the epigenetic treatment that were simultaneously downregulated in primary cholangiocarcinoma compared with controls (n = 43) were investigated for their promoter methylation status in cancer cell lines from the gastrointestinal tract. Genes commonly methylated in cholangiocarcinoma cell lines were subjected to quantitative methylation-specific polymerase chain reaction in a total of 93 clinical samples (cholangiocarcinomas and non-malignant controls). CDO1, DCLK1, SFRP1 and ZSCAN18, displayed high methylation frequencies in primary tumors and were unmethylated in controls. At least one of these four biomarkers was positive in 87% of the tumor samples, with a specificity of 100%. In conclusion, the novel methylation-based biomarker panel showed high sensitivity and specificity for cholangiocarcinoma. The potential of these markers in early diagnosis of this cancer type should be further explored.","Source":"PubMed","category":"ANIMAL","training_data":"Novel target genes and a valid biomarker panel identified for cholangiocarcinoma Cholangiocarcinoma is notoriously difficult to diagnose, and the mortality rate is high due to late clinical presentation. CpG island promoter methylation is frequently seen in cancer development. In the present study, we aimed at identifying novel epigenetic biomarkers with the potential to improve the diagnostic accuracy of cholangiocarcinoma. Microarray data analyses of cholangiocarcinoma cell lines treated with epigenetic drugs and their untreated counterparts were compared with previously published gene expression profiles of primary tumors and with non-malignant controls. Genes responding to the epigenetic treatment that were simultaneously downregulated in primary cholangiocarcinoma compared with controls (n = 43) were investigated for their promoter methylation status in cancer cell lines from the gastrointestinal tract. Genes commonly methylated in cholangiocarcinoma cell lines were subjected to quantitative methylation-specific polymerase chain reaction in a total of 93 clinical samples (cholangiocarcinomas and non-malignant controls). CDO1, DCLK1, SFRP1 and ZSCAN18, displayed high methylation frequencies in primary tumors and were unmethylated in controls. At least one of these four biomarkers was positive in 87% of the tumor samples, with a specificity of 100%. In conclusion, the novel methylation-based biomarker panel showed high sensitivity and specificity for cholangiocarcinoma. The potential of these markers in early diagnosis of this cancer type should be further explored. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"expression levels significance nuclear factor b epidermal growth factor receptor hepatolithiasis associated intrahepatic cholangiocarcinoma background increasing incidence cholangiocarcinoma cca cca mortality rates observed around world patients intrahepatic biliary stones 10 risk developing cca 70 patients histologically confirmed cca hepatolithiasis previous studies addressed associations expression nuclear factor nf b epidermal growth factor receptor egfr clinicopathological prognosis patients hepatolithiasis associated intrahepatic cca aims study designed investigate clinicopathological prognostic significance nf b egfr expression hepatolithiasis associated intrahepatic cca hepatolithiasis methods total 90 liver specimens immunohistochemically stained nf b egfr expression characteristics 90 individual patients retrospectively reviewed results differences positive rates nf b egfr expression hepatolithiasis associated intrahepatic cca group intrahepatic lithiasis group control group found statistically significant egfr expression closely associated degree differentiation depth invasion p 0 05 1 3 5 year overall survival rates respectively 42 8 21 0 10 3 intrahepatic cca groups survival rate egfr negative group higher egfr positive group p 0 01 lymph node metastasis hr 1 24 95 ci 1 02 1 51 egfr positivity hr 1 74 95 ci 1 30 2 23 associated decreases survival rate conclusion expression nf b may early step intrahepatic cholangiocarcinogenesis overexpression egfr associated degree malignancy poor prognosis nf b egfr may cooperate intrahepatic cholangiocarcinogenesis progression lymph node metastasis egfr positivity associated decreases survival rate pubmed","probabilities":0.9799733,"Title":"Expression levels and significance of nuclear factor-κB and epidermal growth factor receptor in hepatolithiasis associated with intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: An increasing incidence of cholangiocarcinoma (CCA) and CCA mortality rates has been observed around the world. Patients with intrahepatic biliary stones have a 10% risk of developing CCA, and up to 70% of patients with histologically confirmed CCA have hepatolithiasis. Few previous studies have addressed the associations between the expression of nuclear factor (NF)-κB and epidermal growth factor receptor (EGFR) and clinicopathological prognosis in patients with hepatolithiasis-associated intrahepatic CCA. AIMS: This study was designed to investigate the clinicopathological and prognostic significance of NF-κB and EGFR expression in hepatolithiasis-associated intrahepatic CCA and hepatolithiasis. METHODS: A total of 90 liver specimens were immunohistochemically stained for NF-κB and EGFR expression, and the characteristics of 90 individual patients were retrospectively reviewed. RESULTS: Differences in the positive rates of NF-κB and EGFR expression between the hepatolithiasis-associated intrahepatic CCA group, intrahepatic lithiasis group, and control group were found to be statistically significant. EGFR expression was closely associated with the degree of differentiation and depth of invasion (p < 0.05). The 1-, 3-, and 5-year overall survival rates were respectively 42.8, 21.0, and 10.3% in intrahepatic CCA groups. The survival rate of the EGFR-negative group was higher than in the EGFR-positive group (p < 0.01). Lymph node metastasis (HR 1.24, 95% CI 1.02-1.51) and EGFR positivity (HR 1.74, 95% CI 1.30-2.23) were associated with decreases in the survival rate. CONCLUSION: The expression of NF-κB may be an early step in intrahepatic cholangiocarcinogenesis. Overexpression of EGFR is associated with the degree of malignancy and with poor prognosis. NF-κB and EGFR may cooperate during intrahepatic cholangiocarcinogenesis and progression. Lymph node metastasis and EGFR positivity were associated with decreases in the survival rate.","Source":"PubMed","category":"HUMAN","training_data":"Expression levels and significance of nuclear factor-κB and epidermal growth factor receptor in hepatolithiasis associated with intrahepatic cholangiocarcinoma BACKGROUND: An increasing incidence of cholangiocarcinoma (CCA) and CCA mortality rates has been observed around the world. Patients with intrahepatic biliary stones have a 10% risk of developing CCA, and up to 70% of patients with histologically confirmed CCA have hepatolithiasis. Few previous studies have addressed the associations between the expression of nuclear factor (NF)-κB and epidermal growth factor receptor (EGFR) and clinicopathological prognosis in patients with hepatolithiasis-associated intrahepatic CCA. AIMS: This study was designed to investigate the clinicopathological and prognostic significance of NF-κB and EGFR expression in hepatolithiasis-associated intrahepatic CCA and hepatolithiasis. METHODS: A total of 90 liver specimens were immunohistochemically stained for NF-κB and EGFR expression, and the characteristics of 90 individual patients were retrospectively reviewed. RESULTS: Differences in the positive rates of NF-κB and EGFR expression between the hepatolithiasis-associated intrahepatic CCA group, intrahepatic lithiasis group, and control group were found to be statistically significant. EGFR expression was closely associated with the degree of differentiation and depth of invasion (p < 0.05). The 1-, 3-, and 5-year overall survival rates were respectively 42.8, 21.0, and 10.3% in intrahepatic CCA groups. The survival rate of the EGFR-negative group was higher than in the EGFR-positive group (p < 0.01). Lymph node metastasis (HR 1.24, 95% CI 1.02-1.51) and EGFR positivity (HR 1.74, 95% CI 1.30-2.23) were associated with decreases in the survival rate. CONCLUSION: The expression of NF-κB may be an early step in intrahepatic cholangiocarcinogenesis. Overexpression of EGFR is associated with the degree of malignancy and with poor prognosis. NF-κB and EGFR may cooperate during intrahepatic cholangiocarcinogenesis and progression. Lymph node metastasis and EGFR positivity were associated with decreases in the survival rate. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact itraconazole first line chemotherapy survival patients distant metastatic biliary tract cancer aim evaluated efficacy safety itraconazole first line chemotherapy patients metastatic biliary tract cancer btc patients methods retrospectively reviewed data patients histologically diagnosed btc distant metastases received one lines chemotherapy subsequent itraconazole chemotherapy results among 28 enrolled patients 26 93 received docetaxel 35 mg m 2 gemcitabine 1 000 mg m 2 carboplatin auc4 day 1 oral itraconazole solution 400 mg days 2 2 repeated every 2 weeks two patients received docetaxel plus itraconazole irinotecan two complete responses 14 partial responses observed response rate 57 median overall survival 12 0 months 160 cycles 21 75 17 61 patients grade 3 4 neutropenia thrombocytopenia respectively two patients 7 experienced febrile neutropenia conclusion combination chemotherapy itraconazole first line chemotherapy promising patients metastatic btc stn","probabilities":0.9799733,"Title":"Impact Of Itraconazole After First-Line Chemotherapy On The Survival Of Patients With Distant Metastatic Biliary Tract Cancer","Abstract":"Aim: We evaluated the efficacy and safety of itraconazole after first-line chemotherapy in patients with metastatic biliary tract cancer (BTC). \r\n\r\n Patients and methods: We retrospectively reviewed data from patients with histologically-diagnosed BTC with distant metastases who had received one or more lines of chemotherapy and subsequent itraconazole chemotherapy. \r\n\r\n Results: Among 28 enrolled patients, 26 (93%) received docetaxel (35 mg/m(2)), gemcitabine (1,000 mg/m(2)), and carboplatin (AUC4) on day 1 and oral itraconazole solution (400 mg) on days -2 to 2, repeated every 2 weeks. Two patients received docetaxel plus itraconazole with irinotecan. Two complete responses and 14 partial responses were observed, with a response rate of 57%. The median overall survival was 12.0 months. During 160 cycles, 21 (75%) and 17 (61%) patients had grade 3/4 neutropenia and thrombocytopenia, respectively. Two patients (7%) experienced febrile neutropenia. \r\n\r\n Conclusion: Combination chemotherapy with itraconazole after first-line chemotherapy is promising for patients with metastatic BTC.","Source":"STN","category":"HUMAN","training_data":"Impact Of Itraconazole After First-Line Chemotherapy On The Survival Of Patients With Distant Metastatic Biliary Tract Cancer Aim: We evaluated the efficacy and safety of itraconazole after first-line chemotherapy in patients with metastatic biliary tract cancer (BTC). \r\n\r\n Patients and methods: We retrospectively reviewed data from patients with histologically-diagnosed BTC with distant metastases who had received one or more lines of chemotherapy and subsequent itraconazole chemotherapy. \r\n\r\n Results: Among 28 enrolled patients, 26 (93%) received docetaxel (35 mg/m(2)), gemcitabine (1,000 mg/m(2)), and carboplatin (AUC4) on day 1 and oral itraconazole solution (400 mg) on days -2 to 2, repeated every 2 weeks. Two patients received docetaxel plus itraconazole with irinotecan. Two complete responses and 14 partial responses were observed, with a response rate of 57%. The median overall survival was 12.0 months. During 160 cycles, 21 (75%) and 17 (61%) patients had grade 3/4 neutropenia and thrombocytopenia, respectively. Two patients (7%) experienced febrile neutropenia. \r\n\r\n Conclusion: Combination chemotherapy with itraconazole after first-line chemotherapy is promising for patients with metastatic BTC. STN","prediction_labels":"HUMAN"},{"cleaned":"epidemiology incidence mortality gallbladder cancer relation development world introduction gallbladder cancer sixth gastrointestinal cancer one common cancers biliary tract awareness incidence mortality disease distribution terms geographical areas study better planning essential prevention gallbladder therefore study performed aim determining incidence mortality gallbladder cancer relationship human development index hdi world 2012 methods study conducted based data world data cancer world bank including hdi components data age specific incidence mortality rate asr every country 2012 getting global cancer project analyze data correlation tests incidence death rates hdi components employed significance level 0 05 using spss software results 2012 178101 cases gallbladder cancer occurred whole world 76844 cases men 101257 women sex ratio 0 75 2012 142823 deaths gallbladder cancer occurred worldwide 60339 cases men 82484 cases women sex ratio 0 73 positive correlation 0 402 seen gallbladder cancer standardized incidence rate hdi correlation statistically significant p 0 001 also positive correlation 0 261 seen standardized mortality rate gallbladder cancer hdi association statistically significant p 0 001 conclusion countries high incidence gall bladder carcinoma higher mortality rates significant correlation seen standardized incidence mortality rate gallbladder cancer hdi dimensions life expectancy birth average education studies causes disease useful google scholar","probabilities":0.8684211,"Title":"Epidemiology Incidence And Mortality Of Gallbladder Cancer And Its Relation With Development In The World","Abstract":"Introduction: Gallbladder cancer is the sixth gastrointestinal cancer and one of the most common cancers of the biliary tract. Awareness about the incidence and mortality of this disease and its distribution in terms of geographical areas for further study and better planning is essential for prevention gallbladder. Therefore, this study was performed with the aim of determining the incidence and mortality of gallbladder cancer and its relationship with the Human Development Index (HDI) in the world in 2012. Methods: The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Data about the age-specific incidence and mortality rate (ASR) for every country in 2012 were getting from the global cancer project. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. Results: In 2012, 178101 cases of gallbladder cancer had occurred in the whole world that 76844 cases of them were men and 101257 were women (Sex Ratio = 0.75). In 2012, 142823 deaths from gallbladder cancer had occurred in worldwide that 60339 cases were men and 82484 cases were women (Sex Ratio = 0.73). A positive correlation of 0.402 was seen between gallbladder cancer standardized incidence rate and the HDI that this correlation was statistically significant (P < 0.001). Also, a positive correlation of 0.261 was seen between the standardized mortality rate of gallbladder cancer and the HDI that this association was statistically significant (P = 0.001). Conclusion: Countries with high incidence of gall bladder carcinoma have higher mortality rates too. A significant correlation was seen between the standardized incidence and mortality rate of gallbladder cancer and the HDI and its dimensions (life expectancy at birth, average education). Further studies about the causes of this disease can be useful.","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology Incidence And Mortality Of Gallbladder Cancer And Its Relation With Development In The World Introduction: Gallbladder cancer is the sixth gastrointestinal cancer and one of the most common cancers of the biliary tract. Awareness about the incidence and mortality of this disease and its distribution in terms of geographical areas for further study and better planning is essential for prevention gallbladder. Therefore, this study was performed with the aim of determining the incidence and mortality of gallbladder cancer and its relationship with the Human Development Index (HDI) in the world in 2012. Methods: The study was conducted based on data from the world data of cancer and the World Bank (including the HDI and its components). Data about the age-specific incidence and mortality rate (ASR) for every country in 2012 were getting from the global cancer project. To analyze data, correlation tests between incidence and death rates, and HDI and its components were employed with a significance level of 0.05 using SPSS software. Results: In 2012, 178101 cases of gallbladder cancer had occurred in the whole world that 76844 cases of them were men and 101257 were women (Sex Ratio = 0.75). In 2012, 142823 deaths from gallbladder cancer had occurred in worldwide that 60339 cases were men and 82484 cases were women (Sex Ratio = 0.73). A positive correlation of 0.402 was seen between gallbladder cancer standardized incidence rate and the HDI that this correlation was statistically significant (P < 0.001). Also, a positive correlation of 0.261 was seen between the standardized mortality rate of gallbladder cancer and the HDI that this association was statistically significant (P = 0.001). Conclusion: Countries with high incidence of gall bladder carcinoma have higher mortality rates too. A significant correlation was seen between the standardized incidence and mortality rate of gallbladder cancer and the HDI and its dimensions (life expectancy at birth, average education). Further studies about the causes of this disease can be useful. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"feasibility efficacy gemcitabine plus cisplatin combination therapy curative resection biliary tract cancer background aim multi institutional study assess feasibility efficacy gemcitabine plus cisplatin cddp combination therapy gc therapy biliary tract cancer btc adjuvant setting methods eligible patients identified january 2008 january 2013 enrolled gc therapy 1 000 mg m2 gemcitabine 25 mg m2 cddp days 1 8 repeated every 3 weeks performed 6 months primary endpoint feasibility adverse events secondary endpoint recurrence free survival rfs overall survival os results among 29 evaluable patients protocol completed 21 72 patients relative dose intensity rdi gemcitabine cddp 77 81 respectively difference completion rate rdi patients underwent resection vs without major hepatectomy grade 3 4 toxicities included leukopenia 14 neutropenia 27 two year rfs 2 year os 59 90 respectively conclusions standard dose gc therapy tolerable patients btc underwent curative resection either without major hepatectomy survival effect regimen promising comparative study needed google scholar","probabilities":0.9799733,"Title":"Feasibility And Efficacy Of Gemcitabine Plus Cisplatin Combination Therapy After Curative Resection For Biliary Tract Cancer","Abstract":"Background\nThe aim of this multi‐institutional study was to assess the feasibility and the efficacy of gemcitabine plus cisplatin (CDDP) combination therapy (GC therapy) for biliary tract cancer (BTC) in the adjuvant setting.\nMethods\nEligible patients identified between January 2008 and January 2013 were enrolled. GC therapy at 1,000 mg/m2 of gemcitabine and 25 mg/m2 of CDDP on days 1 and 8 repeated every 3 weeks was performed for 6 months. The primary endpoint was the feasibility and the adverse events, and the secondary endpoint was recurrence‐free survival (RFS) and overall survival (OS). \nResults\nAmong 29 evaluable patients, the protocol was completed in 21 (72%) patients. Relative dose intensity (RDI) of gemcitabine and CDDP was 77% and 81%, respectively. There was no difference in the completion rate and the RDI between patients who underwent resection with vs. without major hepatectomy. Grade 3–4 toxicities included leukopenia (14%) and neutropenia (27%). Two‐year RFS and 2‐year OS was 59% and 90%, respectively.\nConclusions\nStandard dose of GC therapy is tolerable in patients with BTC who underwent curative resection either with or without major hepatectomy. The survival effect of this regimen is promising, but further comparative study is needed.","Source":"Google Scholar","category":"HUMAN","training_data":"Feasibility And Efficacy Of Gemcitabine Plus Cisplatin Combination Therapy After Curative Resection For Biliary Tract Cancer Background\nThe aim of this multi‐institutional study was to assess the feasibility and the efficacy of gemcitabine plus cisplatin (CDDP) combination therapy (GC therapy) for biliary tract cancer (BTC) in the adjuvant setting.\nMethods\nEligible patients identified between January 2008 and January 2013 were enrolled. GC therapy at 1,000 mg/m2 of gemcitabine and 25 mg/m2 of CDDP on days 1 and 8 repeated every 3 weeks was performed for 6 months. The primary endpoint was the feasibility and the adverse events, and the secondary endpoint was recurrence‐free survival (RFS) and overall survival (OS). \nResults\nAmong 29 evaluable patients, the protocol was completed in 21 (72%) patients. Relative dose intensity (RDI) of gemcitabine and CDDP was 77% and 81%, respectively. There was no difference in the completion rate and the RDI between patients who underwent resection with vs. without major hepatectomy. Grade 3–4 toxicities included leukopenia (14%) and neutropenia (27%). Two‐year RFS and 2‐year OS was 59% and 90%, respectively.\nConclusions\nStandard dose of GC therapy is tolerable in patients with BTC who underwent curative resection either with or without major hepatectomy. The survival effect of this regimen is promising, but further comparative study is needed. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"predictors incidental gallbladder cancer patients undergoing cholecystectomy benign gallbladder disease abstract background objectives discovery incidental gallbladder cancer igc become frequent due adoption laparoscopy gallbladder spillage operation disseminate cancer worsen prognosis methods patients underwent laparoscopic open cholecystectomy benign gallbladder disease january 1996 august 2011 two tertiary care facilities reviewed unmatched controls randomly selected 2 1 ratio preoperative variables compared two groups results sixty seven patients igc identified compared 134 controls mean age 68 index cases 49 controls 70 cases 75 controls female multivariate analysis showed higher risk igc significantly associated age 65 10 61 p 0 0001 dilated bile ducts 4 76 p 0 0028 presence gallbladder wall thickening 4 39 p 0 0003 model yielded good area curve receiver operating characteristic auc 0 83 discriminating patients igc controls conclusions igc likely found patients age 65 dilated bile ducts gallbladder wall thickening preoperative suspicion gallbladder cancer prompt surgeon careful perforate gallbladder laparoscopic approach lower threshold conversion necessary google scholar","probabilities":0.9799733,"Title":"Predictors Of Incidental Gallbladder Cancer In Patients Undergoing Cholecystectomy For Benign Gallbladder Disease","Abstract":"Abstract \nBackground and Objectives\nDiscovery of incidental gallbladder cancer (IGC) has become more frequent due to adoption of laparoscopy. Gallbladder spillage during operation can disseminate cancer and worsen the prognosis.\nMethods\nPatients who underwent laparoscopic or open cholecystectomy for benign gallbladder disease January 1996 to August 2011 at two tertiary care facilities were reviewed. Unmatched controls were randomly selected in 2:1 ratio. Preoperative variables were compared between the two groups.\nResults\nSixty‐seven patients with IGC were identified and compared to 134 controls. Mean age was 68 for index cases and 49 for controls; 70% of cases and 75% of controls were female. Multivariate analysis showed that higher risk of IGC was significantly associated with age ≥ 65 (OR = 10.61, P  < 0.0001), dilated bile ducts (OR = 4.76, P  = 0.0028), and presence of gallbladder wall thickening (OR = 4.39, P  = 0.0003). This model yielded a very good area under the curve of receiver operating characteristic (AUC = 0.83) for discriminating the patients with IGC from controls. \nConclusions\nIGC is more likely to be found in patients when age is ≥65, with dilated bile ducts and gallbladder wall thickening. Preoperative suspicion of gallbladder cancer should prompt the surgeon to be more careful not to perforate the gallbladder during laparoscopic approach, and to have a lower threshold for conversion if necessary.","Source":"Google Scholar","category":"HUMAN","training_data":"Predictors Of Incidental Gallbladder Cancer In Patients Undergoing Cholecystectomy For Benign Gallbladder Disease Abstract \nBackground and Objectives\nDiscovery of incidental gallbladder cancer (IGC) has become more frequent due to adoption of laparoscopy. Gallbladder spillage during operation can disseminate cancer and worsen the prognosis.\nMethods\nPatients who underwent laparoscopic or open cholecystectomy for benign gallbladder disease January 1996 to August 2011 at two tertiary care facilities were reviewed. Unmatched controls were randomly selected in 2:1 ratio. Preoperative variables were compared between the two groups.\nResults\nSixty‐seven patients with IGC were identified and compared to 134 controls. Mean age was 68 for index cases and 49 for controls; 70% of cases and 75% of controls were female. Multivariate analysis showed that higher risk of IGC was significantly associated with age ≥ 65 (OR = 10.61, P  < 0.0001), dilated bile ducts (OR = 4.76, P  = 0.0028), and presence of gallbladder wall thickening (OR = 4.39, P  = 0.0003). This model yielded a very good area under the curve of receiver operating characteristic (AUC = 0.83) for discriminating the patients with IGC from controls. \nConclusions\nIGC is more likely to be found in patients when age is ≥65, with dilated bile ducts and gallbladder wall thickening. Preoperative suspicion of gallbladder cancer should prompt the surgeon to be more careful not to perforate the gallbladder during laparoscopic approach, and to have a lower threshold for conversion if necessary. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"endoscopic radiofrequency ablation versus photodynamic therapy treatment unresectable cholangiocarcinoma comparison survival safety profiles background cholangiocarcioma cca cancer extremely poor survival 5 year survival low 5 10 published literature median survival 3 6 months unresectable disease relief biliary obstruction endoscopic plastic metal stenting percutaneous drainage mainstay palliative therapies techniques limited life prolonging results photodynamic therapy pdt radiofrequency ablation rfa newer endoscopic technologies allow palliation good safety profiles improved survival compared stent placement alone however little data exists comparing modality benefit palliative therapy prolongation life particularly unresectable cases meta analysis aims evaluate survival benefit pdt compared rfa patients unresectable cca secondarily assess safety outcomes two modalities methods pubmed search made published studies abstracts comparing pdt rfa treatment unresectable cholangiocarcinoma pooled data used generate kaplan meier survival curve log rank test performed assess statistically significant differences survival results twenty four studies found literature search two provided data contingent direct comparison survival patients unresectable cca underwent pdt rfa total 105 patients analyzed 49 underwent rfa 56 underwent pdt median survival rfa group 11 3 months significantly longer median survival pdt group 8 5 months figure 1 p 0 02 safety outcomes tabulated three pooled studies figure 2 rfa found significantly higher stent occlusion p 0 008 cholangitis p 0 001 pdt significantly higher rates stent migration p 0 04 moderate severe post procedural abdominal pain p 0 003 conclusion endoscopic rfa appears significantly greater effect patient survival also associated higher rates stent occlusion cholangitis randomized prospective studies necessary delineate differences treatment methods google scholar","probabilities":0.9799733,"Title":"Endoscopic Radiofrequency Ablation Versus Photodynamic Therapy For The Treatment Of Unresectable Cholangiocarcinoma: Comparison Of Survival And Safety Profiles","Abstract":"Background\nCholangiocarcioma (CCA) is a cancer with extremely poor survival, with 5-year survival as low as 5-10% in the published literature, and a median survival of 3 to 6 months for unresectable disease. While relief of biliary obstruction with endoscopic (plastic or metal stenting) or percutaneous drainage have been the mainstay of palliative therapies, these techniques are limited in their life-prolonging results. Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are newer endoscopic technologies that allow for palliation with good safety profiles and improved survival compared with stent placement alone. However, little data exists comparing each modality’s benefit as palliative therapy and prolongation of life, particularly in unresectable cases. Our meta-analysis aims to evaluate the survival benefit of PDT compared to RFA in patients with unresectable CCA and to secondarily assess safety outcomes of the two modalities.\nMethods\nA PubMed search was made for published studies and abstracts comparing PDT and RFA in the treatment of unresectable cholangiocarcinoma. Pooled data were used to generate a Kaplan-Meier survival curve with log-rank test performed to assess for statistically significant differences in survival\nResults\nTwenty-four studies were found in the literature search, two of which provided data contingent for direct comparison of survival in patients with unresectable CCA who underwent PDT and RFA. A total of 105 patients were analyzed, 49 who underwent RFA and 56 who underwent PDT. Median survival in the RFA group was 11.3 months, which was significantly longer than the median survival in the PDT group of 8.5 months (Figure 1, p = 0.02).\nSafety outcomes were tabulated from three pooled studies (Figure 2). RFA was found to have significantly higher stent occlusion (p= 0.008) and cholangitis (p= 0.001), while PDT had significantly higher rates of stent migration (p = 0.04) and moderate/severe post-procedural abdominal pain (p = 0.003).\nConclusion\nEndoscopic RFA appears to have a significantly greater effect on patient survival but is also associated with higher rates of stent occlusion and cholangitis. More randomized, prospective studies are necessary to further delineate differences between these treatment methods.","Source":"Google Scholar","category":"HUMAN","training_data":"Endoscopic Radiofrequency Ablation Versus Photodynamic Therapy For The Treatment Of Unresectable Cholangiocarcinoma: Comparison Of Survival And Safety Profiles Background\nCholangiocarcioma (CCA) is a cancer with extremely poor survival, with 5-year survival as low as 5-10% in the published literature, and a median survival of 3 to 6 months for unresectable disease. While relief of biliary obstruction with endoscopic (plastic or metal stenting) or percutaneous drainage have been the mainstay of palliative therapies, these techniques are limited in their life-prolonging results. Photodynamic therapy (PDT) and radiofrequency ablation (RFA) are newer endoscopic technologies that allow for palliation with good safety profiles and improved survival compared with stent placement alone. However, little data exists comparing each modality’s benefit as palliative therapy and prolongation of life, particularly in unresectable cases. Our meta-analysis aims to evaluate the survival benefit of PDT compared to RFA in patients with unresectable CCA and to secondarily assess safety outcomes of the two modalities.\nMethods\nA PubMed search was made for published studies and abstracts comparing PDT and RFA in the treatment of unresectable cholangiocarcinoma. Pooled data were used to generate a Kaplan-Meier survival curve with log-rank test performed to assess for statistically significant differences in survival\nResults\nTwenty-four studies were found in the literature search, two of which provided data contingent for direct comparison of survival in patients with unresectable CCA who underwent PDT and RFA. A total of 105 patients were analyzed, 49 who underwent RFA and 56 who underwent PDT. Median survival in the RFA group was 11.3 months, which was significantly longer than the median survival in the PDT group of 8.5 months (Figure 1, p = 0.02).\nSafety outcomes were tabulated from three pooled studies (Figure 2). RFA was found to have significantly higher stent occlusion (p= 0.008) and cholangitis (p= 0.001), while PDT had significantly higher rates of stent migration (p = 0.04) and moderate/severe post-procedural abdominal pain (p = 0.003).\nConclusion\nEndoscopic RFA appears to have a significantly greater effect on patient survival but is also associated with higher rates of stent occlusion and cholangitis. More randomized, prospective studies are necessary to further delineate differences between these treatment methods. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"hepatocellular carcinoma associated lipid metabolism reprogramming background hepatocellular carcinoma hcc primary malignancy liver high worldwide prevalence poor prognosis previous data affymetrix microarray analysis shown decrease genes involved phospholipid catabolism fatty acid catabolism choline metabolism bile acid metabolism hcc compared control tissue aim study better understand metabolic processes relation development hcc materials methods tumor plasma bile samples collected time hepatic resection hcc bile specimens collected gallbladder beginning case normal bile plasma collected patients undergoing cholecystectomy non neoplastic disease liver biopsy samples taken tumor adjacent normal tissue phospholipid levels evaluated enzyme linked immunosorbent assay elisa high performance thin layer chromatography hptlc results targeted phospholipid analysis hptlc elisa showed modified choline metabolic profile within liver bile serum culminating increased synthesis lysophosphatidic acid lpa choline significantly increased tumor tissue lysophosphatidylcholine lpc increased within bile lpa increased three biological samples hcc patients compared controls phosphatidylcholine significantly changed conclusions hcc congruent reprogramming choline catabolism phospholipid metabolism increased lpa may provide potent mitogenic proliferative microenvironment via autocrine paracrine activation high affinity g protein coupled receptors additional research required better understand role pathways hcc development pubmed","probabilities":0.7966102,"Title":"Hepatocellular carcinoma associated lipid metabolism reprogramming","Abstract":"BACKGROUND: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high worldwide prevalence and poor prognosis. Previous data, by Affymetrix microarray analysis, has shown a decrease in genes involved in phospholipid catabolism, fatty acid catabolism, choline metabolism, and bile acid metabolism in HCC compared with control tissue. The aim of this study was to better understand metabolic processes in relation to the development of HCC. MATERIALS AND METHODS: Tumor, plasma, and bile samples were collected at the time of hepatic resection for HCC. All bile specimens were collected from the gallbladder at the beginning of the case. Normal bile and plasma were collected from patients undergoing cholecystectomy for non-neoplastic disease. Liver biopsy samples were taken from both tumor and adjacent normal tissue. Phospholipid levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and high performance thin layer chromatography (HPTLC). RESULTS: Targeted phospholipid analysis by HPTLC and ELISA showed a modified choline metabolic profile within the liver, bile, and serum, culminating in an increased synthesis of lysophosphatidic acid (LPA). Choline was significantly increased in tumor tissue; lysophosphatidylcholine (LPC) was increased within bile while LPA was increased in all three biological samples of HCC patients compared with controls. Phosphatidylcholine was not significantly changed. CONCLUSIONS: HCC is congruent with a reprogramming of choline catabolism and phospholipid metabolism. Increased LPA may provide a potent mitogenic and proliferative microenvironment via autocrine/paracrine activation of high-affinity G-protein-coupled receptors. Additional research is required to better understand the role of these pathways in HCC development.","Source":"PubMed","category":"ANIMAL","training_data":"Hepatocellular carcinoma associated lipid metabolism reprogramming BACKGROUND: Hepatocellular carcinoma (HCC) is a primary malignancy of the liver with a high worldwide prevalence and poor prognosis. Previous data, by Affymetrix microarray analysis, has shown a decrease in genes involved in phospholipid catabolism, fatty acid catabolism, choline metabolism, and bile acid metabolism in HCC compared with control tissue. The aim of this study was to better understand metabolic processes in relation to the development of HCC. MATERIALS AND METHODS: Tumor, plasma, and bile samples were collected at the time of hepatic resection for HCC. All bile specimens were collected from the gallbladder at the beginning of the case. Normal bile and plasma were collected from patients undergoing cholecystectomy for non-neoplastic disease. Liver biopsy samples were taken from both tumor and adjacent normal tissue. Phospholipid levels were evaluated by enzyme-linked immunosorbent assay (ELISA) and high performance thin layer chromatography (HPTLC). RESULTS: Targeted phospholipid analysis by HPTLC and ELISA showed a modified choline metabolic profile within the liver, bile, and serum, culminating in an increased synthesis of lysophosphatidic acid (LPA). Choline was significantly increased in tumor tissue; lysophosphatidylcholine (LPC) was increased within bile while LPA was increased in all three biological samples of HCC patients compared with controls. Phosphatidylcholine was not significantly changed. CONCLUSIONS: HCC is congruent with a reprogramming of choline catabolism and phospholipid metabolism. Increased LPA may provide a potent mitogenic and proliferative microenvironment via autocrine/paracrine activation of high-affinity G-protein-coupled receptors. Additional research is required to better understand the role of these pathways in HCC development. PubMed","prediction_labels":"HUMAN"},{"cleaned":"neutrophil lymphocyte ratio platelet lymphocyte ratio dynamic changes chemotherapy useful predict accurate prognosis advanced biliary tract cancer background purpose systemic inflammation known promote carcinogenesis biliary tract cancer btc neutrophil lymphocyte ratio nlr platelet lymphocyte ratio plr indicative systemic inflammation evaluated clinical significance systemic inflammation measured nlr plr patients advanced btc additionally also co analyzed dynamics nlr plr chemotherapy methods reviewed 450 patients unresectable btc receiving palliative chemotherapy nlr plr obtained initiation palliative chemotherapy changes nlr plr obtained subtracting initial value value obtained progression chemotherapy results higher systemic inflammation status also relation primary tumor site p 0 003 higher levels cea p 0 038 roc cut values nlr plr predicting overall survival os 3 8 121 respectively patients high nlr plr worse os independently multivariate analysis 6 90 vs 9 80 months p 0 002 7 83 vs 9 90 months p 0 041 respectively high nlr increased nlr chemotherapy associated worse os progression free survival pfs p 0 001 p 0 013 respectively results similar plr conclusion systemic inflammation represented nlr plr predicts os patients advanced btc receiving palliative chemotherapy addition considering nlr plr dynamic change nlr plr chemotherapy might help predict accurate prognosis pubmed","probabilities":0.9799733,"Title":"Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and their dynamic changes during chemotherapy is useful to predict a more accurate prognosis of advanced biliary tract cancer","Abstract":"BACKGROUND AND PURPOSE: Systemic inflammation is known to promote carcinogenesis in biliary tract cancer (BTC). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are indicative of systemic inflammation. We evaluated the clinical significance of systemic inflammation measured by NLR and PLR in patients with advanced BTC. Additionally, we also co-analyzed the dynamics of NLR and PLR during chemotherapy. METHODS: We reviewed 450 patients with unresectable BTC receiving palliative chemotherapy. NLR and PLR were obtained before initiation of palliative chemotherapy. Changes in NLR, PLR were obtained by subtracting the initial value from the value obtained after progression of chemotherapy. RESULTS: Higher systemic inflammation status also had relation with a primary tumor site (p = 0.003) and higher levels of CEA (p = 0.038). The ROC cut-off values of NLR and PLR for predicting overall survival (OS) were 3.8 and 121, respectively. Patients with a high NLR or PLR had worse OS independently in multivariate analysis (6.90 vs. 9.80 months, p =0.002; 7.83 vs. 9.90 months, p =0.041, respectively). High NLR with increased NLR after chemotherapy is associated with worse OS and progression-free survival (PFS) (p < 0.001, p = 0.013 respectively). Results are similar for PLR. CONCLUSION: Systemic inflammation represented by NLR and PLR, predicts the OS of patients with advanced BTC who are receiving palliative chemotherapy. In addition, considering NLR/PLR with a dynamic change of NLR/PLR during chemotherapy might help to predict a more accurate prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and their dynamic changes during chemotherapy is useful to predict a more accurate prognosis of advanced biliary tract cancer BACKGROUND AND PURPOSE: Systemic inflammation is known to promote carcinogenesis in biliary tract cancer (BTC). Neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) are indicative of systemic inflammation. We evaluated the clinical significance of systemic inflammation measured by NLR and PLR in patients with advanced BTC. Additionally, we also co-analyzed the dynamics of NLR and PLR during chemotherapy. METHODS: We reviewed 450 patients with unresectable BTC receiving palliative chemotherapy. NLR and PLR were obtained before initiation of palliative chemotherapy. Changes in NLR, PLR were obtained by subtracting the initial value from the value obtained after progression of chemotherapy. RESULTS: Higher systemic inflammation status also had relation with a primary tumor site (p = 0.003) and higher levels of CEA (p = 0.038). The ROC cut-off values of NLR and PLR for predicting overall survival (OS) were 3.8 and 121, respectively. Patients with a high NLR or PLR had worse OS independently in multivariate analysis (6.90 vs. 9.80 months, p =0.002; 7.83 vs. 9.90 months, p =0.041, respectively). High NLR with increased NLR after chemotherapy is associated with worse OS and progression-free survival (PFS) (p < 0.001, p = 0.013 respectively). Results are similar for PLR. CONCLUSION: Systemic inflammation represented by NLR and PLR, predicts the OS of patients with advanced BTC who are receiving palliative chemotherapy. In addition, considering NLR/PLR with a dynamic change of NLR/PLR during chemotherapy might help to predict a more accurate prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative prognostic nutritional index predicts survival patients intrahepatic cholangiocarcinoma curative resection background intrahepatic cholangiocarcinoma icc aggressive malignancy sought examine association preoperative prognostic nutritional index pni long term overall survival among patients icc underwent curative intent resection methods patients underwent hepatectomy icc 1990 2015 identified using international multi institutional database clinic pathological characteristics long term outcomes patients pni 40 40 compared using univariable multivariable analyses results among 637 patients 53 patients pni 40 8 3 584 patients pni 40 91 7 difference pni groups regard tumor size p 87 patients pni 40 likely multifocal disease pni 40 n 16 30 2 vs pni 40 n 65 11 1 p 0 001 poorly differentiated undifferentiated icc pni 40 n 13 25 5 vs pni 40 n 75 13 1 p 0 020 t2 t3 t4 disease vs patients pni 40 pni 40 n 38 71 7 vs pni 40 n 265 45 4 p 0 001 patients pni 40 better os vs patients pni 40 5 year os pni 40 47 5 95 ci 42 2 52 6 vs pni 40 24 6 95 ci 12 1 39 6 p 0 001 multivariable analysis pni 40 remained associated increase risk death hr 1 71 95 ci 1 15 2 53 p 0 008 conclusion low preoperative pni associated aggressive icc phenotype controlling factors pni remained independently associated markedly worse prognosis pubmed","probabilities":0.9799733,"Title":"Preoperative prognostic nutritional index predicts survival of patients with intrahepatic cholangiocarcinoma after curative resection","Abstract":"BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy. We sought to examine the association between preoperative prognostic nutritional index (PNI) and long-term overall survival among patients with ICC who underwent curative-intent resection. METHODS: Patients who underwent hepatectomy for ICC between 1990 and 2015 were identified using an international multi-institutional database. Clinic-pathological characteristics and long-term outcomes of patients with PNI ≥ 40 and <40 were compared using univariable and multivariable analyses. RESULTS: Among 637 patients, 53 patients had PNI < 40 (8.3%) and 584 patients had PNI ≥ 40 (91.7%). While there was no difference between PNI groups with regard to tumor size (P = .87), patients with PNI < 40 were more likely to have multifocal disease (PNI < 40, n = 16, 30.2% vs PNI ≥ 40, n = 65, 11.1%; P < 0.001), poorly differentiated or undifferentiated ICC (PNI < 40, n = 13, 25.5% vs PNI ≥ 40, n = 75, 13.1%; P = 0.020) and T2/T3/T4 disease vs patients with PNI ≥ 40 (PNI < 40, n = 38, 71.7% vs PNI ≥ 40, n = 265, 45.4%; P < 0.001). Patients with PNI ≥ 40 had better OS vs patients with PNI < 40 (5-year OS: PNI ≥ 40: 47.5%, 95% CI, 42.2 to 52.6% vs PNI < 40: 24.6%, 95% CI, 12.1 to 39.6%; P < 0.001). On multivariable analysis, PNI < 40 remained associated with increase risk of death (HR, 1.71; 95% CI, 1.15 to 2.53; P = 0.008). CONCLUSION: A low preoperative PNI was associated with a more aggressive ICC phenotype. After controlling for these factors, PNI remained independently associated with a markedly worse prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Preoperative prognostic nutritional index predicts survival of patients with intrahepatic cholangiocarcinoma after curative resection BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is an aggressive malignancy. We sought to examine the association between preoperative prognostic nutritional index (PNI) and long-term overall survival among patients with ICC who underwent curative-intent resection. METHODS: Patients who underwent hepatectomy for ICC between 1990 and 2015 were identified using an international multi-institutional database. Clinic-pathological characteristics and long-term outcomes of patients with PNI ≥ 40 and <40 were compared using univariable and multivariable analyses. RESULTS: Among 637 patients, 53 patients had PNI < 40 (8.3%) and 584 patients had PNI ≥ 40 (91.7%). While there was no difference between PNI groups with regard to tumor size (P = .87), patients with PNI < 40 were more likely to have multifocal disease (PNI < 40, n = 16, 30.2% vs PNI ≥ 40, n = 65, 11.1%; P < 0.001), poorly differentiated or undifferentiated ICC (PNI < 40, n = 13, 25.5% vs PNI ≥ 40, n = 75, 13.1%; P = 0.020) and T2/T3/T4 disease vs patients with PNI ≥ 40 (PNI < 40, n = 38, 71.7% vs PNI ≥ 40, n = 265, 45.4%; P < 0.001). Patients with PNI ≥ 40 had better OS vs patients with PNI < 40 (5-year OS: PNI ≥ 40: 47.5%, 95% CI, 42.2 to 52.6% vs PNI < 40: 24.6%, 95% CI, 12.1 to 39.6%; P < 0.001). On multivariable analysis, PNI < 40 remained associated with increase risk of death (HR, 1.71; 95% CI, 1.15 to 2.53; P = 0.008). CONCLUSION: A low preoperative PNI was associated with a more aggressive ICC phenotype. After controlling for these factors, PNI remained independently associated with a markedly worse prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"seer based multi ethnic picture advanced intrahepatic cholangiocarcinoma united states pre post advent gemcitabine cisplatin background cholangiocarcinoma cca rare lethal cancer 5 year survival less 10 although incidence rates increasing united states ethnic variations survival investigated examined multi ethnic variation overall survival os cca specific survival css using data population based surveillance epidemiology end results seer program 4 year period introduction gemcitabine cisplatin gc treatment cca compared prior years methods study included data 5 616 advanced intrahepatic cca cases reported seer 1990 2013 multivariable adjusted hazard ratios hr 95 confidence intervals cis calculated examine os css ethnicity age gender pre post gc era 1990 2000 2001 2009 vs 2010 2013 results compared non hispanic whites hispanics poorer 3 year os hr 1 11 95 ci 1 03 1 20 3 year css hr 1 15 95 ci 1 05 1 25 similarly non hispanic blacks 3 year os hr 1 21 95 ci 1 10 1 34 3 year css hr 1 21 95 ci 1 09 1 35 males older patients shorter survival compared females younger patients os css improved patients post advent gc statistically significant improvement css pre post advent gc noted non hispanic whites hispanics actually worsened survival conclusions hispanics non hispanic blacks worse survival diagnosis advanced intrahepatic cca studies needed determine determinants poor survival among groups stn","probabilities":0.9799733,"Title":"A Seer-Based Multi-Ethnic Picture Of Advanced Intrahepatic Cholangiocarcinoma In The United States Pre- And Post-The Advent Of Gemcitabine/Cisplatin","Abstract":"Background: Cholangiocarcinoma (CCA) is a rare, lethal cancer with 5-year survival of less than 10%. Although incidence rates have been increasing in the United States, ethnic variations in survival have not been investigated. We examined multi-ethnic variation in overall survival (OS) and CCA-specific survival (CSS) using data from the population-based Surveillance Epidemiology and End Results (SEER) program in the 4-year period after introduction of gemcitabine/cisplatin (GC) as treatment for CCA, compared with prior years. \r\n\r\n Methods: The study included data from 5,616 advanced, intrahepatic CCA cases reported in SEER between 1990 and 2013. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated to examine OS and CSS by ethnicity, age, gender and in the pre- and post-GC era (1990-2000, 2001-2009 vs. 2010-2013). \r\n\r\n Results: Compared to non-Hispanic Whites, Hispanics had poorer 3-year OS (HR 1.11, 95% CI: 1.03-1.20) and 3-year CSS (HR 1.15, 95% CI: 1.05-1.25). Similarly, non-Hispanic Blacks had 3-year OS (HR 1.21, 95% CI: 1.10-1.34) and 3-year CSS (HR 1.21, 95% CI: 1.09-1.35). Males and older patients had shorter survival compared to females and younger patients. OS and CSS were both improved for patients' post-advent of GC. Statistically significant improvement in CSS pre- and post-advent of GC was noted in non-Hispanic Whites, while Hispanics actually had worsened survival. \r\n\r\n Conclusions: Hispanics and non-Hispanic Blacks have worse survival after diagnosis with advanced, intrahepatic CCA. Further studies are needed to determine determinants of poor survival among these groups.","Source":"STN","category":"HUMAN","training_data":"A Seer-Based Multi-Ethnic Picture Of Advanced Intrahepatic Cholangiocarcinoma In The United States Pre- And Post-The Advent Of Gemcitabine/Cisplatin Background: Cholangiocarcinoma (CCA) is a rare, lethal cancer with 5-year survival of less than 10%. Although incidence rates have been increasing in the United States, ethnic variations in survival have not been investigated. We examined multi-ethnic variation in overall survival (OS) and CCA-specific survival (CSS) using data from the population-based Surveillance Epidemiology and End Results (SEER) program in the 4-year period after introduction of gemcitabine/cisplatin (GC) as treatment for CCA, compared with prior years. \r\n\r\n Methods: The study included data from 5,616 advanced, intrahepatic CCA cases reported in SEER between 1990 and 2013. Multivariable-adjusted hazard ratios (HR) and 95% confidence intervals (CIs) were calculated to examine OS and CSS by ethnicity, age, gender and in the pre- and post-GC era (1990-2000, 2001-2009 vs. 2010-2013). \r\n\r\n Results: Compared to non-Hispanic Whites, Hispanics had poorer 3-year OS (HR 1.11, 95% CI: 1.03-1.20) and 3-year CSS (HR 1.15, 95% CI: 1.05-1.25). Similarly, non-Hispanic Blacks had 3-year OS (HR 1.21, 95% CI: 1.10-1.34) and 3-year CSS (HR 1.21, 95% CI: 1.09-1.35). Males and older patients had shorter survival compared to females and younger patients. OS and CSS were both improved for patients' post-advent of GC. Statistically significant improvement in CSS pre- and post-advent of GC was noted in non-Hispanic Whites, while Hispanics actually had worsened survival. \r\n\r\n Conclusions: Hispanics and non-Hispanic Blacks have worse survival after diagnosis with advanced, intrahepatic CCA. Further studies are needed to determine determinants of poor survival among these groups. STN","prediction_labels":"HUMAN"},{"cleaned":"aspirin may prevent cholangiocarcinoma case control study united kingdom background proliferation cholangiocarcinoma cells suppressed cell culture nonsteroidal antiinflammatory drugs nsaids inhibition cyclo oxygenase 2 enzyme also statins decrease production mediators cell cycle aims investigate whether inverse association nsaids including aspirin development cholangiocarcinoma first time western population statin use development cholangiocarcinoma methods epidemiological study case control design cases cholangiocarcinoma diagnosed norwich 2004 2010 leicester 2007 identified clinical databases controls patients basal cell carcinomas treated respective dermatology departments case notes subjects reviewed confirm diagnoses obtain information medication use data analyzed using unconditional logistic regression calculate odds ratios 95 confidence intervals ci results total 81 cases cholangiocarcinoma 275 controls identified cases radiological evidence cancer 86 cases involved extrahepatic biliary system aspirin use inversely associated development cholangiocarcinoma 0 45 95 ci 0 22 0 92 significant associations development cholangiocarcinoma nsaids 0 39 95 ci 0 11 1 42 statins 0 58 95 ci 0 28 1 19 conclusions epidemiological data study support biological evidence aspirin protective effect development cholangiocarcinoma aspirin use measured future etiological studies assessed chemoprevention agent high risk developing type cancer stn","probabilities":1.0,"Title":"Aspirin May Prevent Cholangiocarcinoma: A Case-Control Study From The United Kingdom","Abstract":"Background: The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle. \r\n\r\n Aims: To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma. \r\n\r\n Methods: This epidemiological study had a case-control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI). \r\n\r\n Results: In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22-0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11-1.42) or statins (OR 0.58; 95 % CI 0.28-1.19). \r\n\r\n Conclusions: The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer.","Source":"STN","category":"HUMAN","training_data":"Aspirin May Prevent Cholangiocarcinoma: A Case-Control Study From The United Kingdom Background: The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle. \r\n\r\n Aims: To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma. \r\n\r\n Methods: This epidemiological study had a case-control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI). \r\n\r\n Results: In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22-0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11-1.42) or statins (OR 0.58; 95 % CI 0.28-1.19). \r\n\r\n Conclusions: The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"hepatolithiasis followed carefully detect cholangiocarcinoma even completeness stone removal regardless treatment modality background hepatolithiasis well known risk factor cholangiocarcinoma despite advances diagnostic modalities diagnosing cholangiocarcinoma patients hepatolithiasis still challenging enough reports incidence cholangiocarcinoma patient hepatolithiasis treatment aimed evaluate incidence clinical characteristics cholangiocarcinoma patients hepatolithiasis underwent liver resection non resection methods among total 257 patients received treatment hepatolithiasis 236 patients eligible analysis exclusion criteria follow period less 9 months preoperative diagnosis cholangiocarcinoma occurrence cholangiocarcinoma within 1 year treatment completeness stone clearance defined intrahepatic duct stone whole follow period retrospective study done analyze patients characteristics results complications procedure long term outcomes patients kaplan meier method cox proportional regression used statistical analysis results 95 patients underwent hepatic resection resection group 144 patients non resection group complete stone clearance 71 67 95 resection group 41 58 141 non resection group p 0 001 incidence cholangiocarcinoma 6 8 16 236 follow period mean 41 41 months cholangiocarcinoma occurred 6 3 6 95 7 1 10 141 resection non resection group respectively significant difference survival two groups p 0 254 analysis according completeness stone clearance regardless treatment modality cholangiocarcinoma incidence higher patients residual stone 10 4 complete stone removal 3 3 p 0 263 multivariate analysis none factors age gender ca19 9 stone location bile duct stenosis liver atrophy stone recurrence residual stone hepatic resection showed relationship incidence cholangiocarcinoma conclusion hepatic resection hepatolithiasis considered limited value preventing cholangiocarcinoma patients carefully followed even hepatic resection combination different treatment modalities necessary decrease residual stone improve outcome patients hepatolithiasis stn","probabilities":0.9799733,"Title":"Hepatolithiasis Should Be Followed-Up Carefully To Detect Cholangiocarcinoma Even After Completeness Of Stone Removal Regardless Of Treatment Modality","Abstract":"Background: Hepatolithiasis is a well-known risk factor of cholangiocarcinoma. Despite advances in diagnostic modalities, diagnosing cholangiocarcinoma in patients with hepatolithiasis still challenging and there are not enough reports on the incidence of cholangiocarcinoma in patient with hepatolithiasis after treatment. We aimed to evaluate the incidence and clinical characteristics of cholangiocarcinoma in patients with hepatolithiasis who underwent liver resection or non-resection. \r\n\r\n Methods: Among a total of 257 patients who received treatment for hepatolithiasis, 236 patients were eligible for analysis. Exclusion criteria were follow-up period less than 9 months, preoperative diagnosis of cholangiocarcinoma, occurrence of cholangiocarcinoma within 1 year after treatment. Completeness of stone clearance was defined when there was no intrahepatic duct stone during whole follow-up period. A retrospective study was done to analyze the patients' characteristics, the results and complications of the procedure, and the long-term outcomes for these patients. Kaplan-Meier method and cox proportional regression were used for statistical analysis. \r\n\r\n Results: 95 patients underwent hepatic resection (resection group) and 144 patients did not (non-resection group). Complete stone clearance was 71% (67/95) in resection group and 41% (58/141) in non-resection group (p < 0.001). The incidence of cholangiocarcinoma was 6.8% (16/236) during follow-up period (mean 41 ± 41 months). Cholangiocarcinoma occurred 6.3% (6/95) and 7.1% (10/141) in resection and non-resection group, respectively. There was no significant difference in survival between two groups (p = 0.254). In analysis of according to completeness of stone clearance regardless of treatment modality, cholangiocarcinoma incidence was higher in patients with residual stone (10.4%) than complete stone removal (3.3%) (p = 0.263). On multivariate analysis, none of the factors (age, gender, CA19-9, stone location, bile duct stenosis, liver atrophy, stone recurrence, residual stone, and hepatic resection) showed relationship with the incidence of cholangiocarcinoma. \r\n\r\n Conclusion: Hepatic resection for hepatolithiasis is considered to have a limited value in preventing cholangiocarcinoma and the patients should be carefully followed even after hepatic resection. A combination of different treatment modalities is necessary to decrease the residual stone and improve the outcome of the patients with hepatolithiasis.","Source":"STN","category":"HUMAN","training_data":"Hepatolithiasis Should Be Followed-Up Carefully To Detect Cholangiocarcinoma Even After Completeness Of Stone Removal Regardless Of Treatment Modality Background: Hepatolithiasis is a well-known risk factor of cholangiocarcinoma. Despite advances in diagnostic modalities, diagnosing cholangiocarcinoma in patients with hepatolithiasis still challenging and there are not enough reports on the incidence of cholangiocarcinoma in patient with hepatolithiasis after treatment. We aimed to evaluate the incidence and clinical characteristics of cholangiocarcinoma in patients with hepatolithiasis who underwent liver resection or non-resection. \r\n\r\n Methods: Among a total of 257 patients who received treatment for hepatolithiasis, 236 patients were eligible for analysis. Exclusion criteria were follow-up period less than 9 months, preoperative diagnosis of cholangiocarcinoma, occurrence of cholangiocarcinoma within 1 year after treatment. Completeness of stone clearance was defined when there was no intrahepatic duct stone during whole follow-up period. A retrospective study was done to analyze the patients' characteristics, the results and complications of the procedure, and the long-term outcomes for these patients. Kaplan-Meier method and cox proportional regression were used for statistical analysis. \r\n\r\n Results: 95 patients underwent hepatic resection (resection group) and 144 patients did not (non-resection group). Complete stone clearance was 71% (67/95) in resection group and 41% (58/141) in non-resection group (p < 0.001). The incidence of cholangiocarcinoma was 6.8% (16/236) during follow-up period (mean 41 ± 41 months). Cholangiocarcinoma occurred 6.3% (6/95) and 7.1% (10/141) in resection and non-resection group, respectively. There was no significant difference in survival between two groups (p = 0.254). In analysis of according to completeness of stone clearance regardless of treatment modality, cholangiocarcinoma incidence was higher in patients with residual stone (10.4%) than complete stone removal (3.3%) (p = 0.263). On multivariate analysis, none of the factors (age, gender, CA19-9, stone location, bile duct stenosis, liver atrophy, stone recurrence, residual stone, and hepatic resection) showed relationship with the incidence of cholangiocarcinoma. \r\n\r\n Conclusion: Hepatic resection for hepatolithiasis is considered to have a limited value in preventing cholangiocarcinoma and the patients should be carefully followed even after hepatic resection. A combination of different treatment modalities is necessary to decrease the residual stone and improve the outcome of the patients with hepatolithiasis. STN","prediction_labels":"HUMAN"},{"cleaned":"honokiol enhanced cytotoxic lymphocyte activity cholangiocarcinoma cells mediated dendritic cells pulsed damage associated molecular patterns background cholangiocarcinoma biliary tract cancer high mortality rate resulting late presentation ineffective treatment strategy since immunotherapy dendritic cells dc may beneficial cholangiocarcinoma treatment efficacy cholangiocarcinoma low suggest anti tumor activity increased using cell lysates derived honokiol treated cholangiocarcinoma cell line kku 213l5 aim increase antitumour activity dcs pulsed cell lysates derived honokiol treated cholangiocarcinoma cell line kku 213l5 methods effect honokiol phenolic compound isolated magnolia officinalis choangiocarcinoma cells investigated terms cytotoxicity expression damage associated molecular patterns damps dcs loaded tumour cell lysates derived honokiol treated cholangiocarcinoma cells efficacy including induction lymphocyte proliferation proinflammatory cytokine production cytotoxicity effect target cholangiocarcinoma cells evaluated results honokiol effectively activate cholangiocarcinoma apoptosis increase release damage associated molecular patterns dcs loaded cell lysates derived honokiol treated tumour cells enhanced priming stimulated lymphocyte proliferation type cytokine production lymphocytes stimulated dcs pulsed cell lysates honokiol treated tumour cells significantly increased specific killing human cholangiocarcinoma cells compared associated dcs pulsed cell lysates untreated cholangiocarcinoma cells conclusion present findings suggested honokiol able enhance immunogenicity cholangiocarcinoma cells associated increased effectiveness dc based vaccine formulation treatment tumour cells honokiol offers promising approach ex vivo dc based anticancer vaccine stn","probabilities":0.9467213,"Title":"Honokiol-Enhanced Cytotoxic T Lymphocyte Activity Against Cholangiocarcinoma Cells Mediated By Dendritic Cells Pulsed With Damage-Associated Molecular Patterns","Abstract":"Background: Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such anti-tumor activity can be increased using cell lysates derived from an honokiol-treated cholangiocarcinoma cell line (KKU-213L5). \r\n\r\n Aim: To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5). \r\n\r\n Methods: The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated. \r\n\r\n Results: Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells. \r\n\r\n Conclusion: The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine.","Source":"STN","category":"ANIMAL","training_data":"Honokiol-Enhanced Cytotoxic T Lymphocyte Activity Against Cholangiocarcinoma Cells Mediated By Dendritic Cells Pulsed With Damage-Associated Molecular Patterns Background: Cholangiocarcinoma or biliary tract cancer has a high mortality rate resulting from late presentation and ineffective treatment strategy. Since immunotherapy by dendritic cells (DC) may be beneficial for cholangiocarcinoma treatment but their efficacy against cholangiocarcinoma was low. We suggest how such anti-tumor activity can be increased using cell lysates derived from an honokiol-treated cholangiocarcinoma cell line (KKU-213L5). \r\n\r\n Aim: To increase antitumour activity of DCs pulsed with cell lysates derived from honokiol-treated cholangiocarcinoma cell line (KKU-213L5). \r\n\r\n Methods: The effect of honokiol, a phenolic compound isolated from Magnolia officinalis, on choangiocarcinoma cells was investigated in terms of the cytotoxicity and the expression of damage-associated molecular patterns (DAMPs). DCs were loaded with tumour cell lysates derived from honokiol-treated cholangiocarcinoma cells their efficacy including induction of T lymphocyte proliferation, proinflammatory cytokine production and cytotoxicity effect on target cholangiocarcinoma cells were evaluated. \r\n\r\n Results: Honokiol can effectively activate cholangiocarcinoma apoptosis and increase the release of damage-associated molecular patterns. DCs loaded with cell lysates derived from honokiol-treated tumour cells enhanced priming and stimulated T lymphocyte proliferation and type I cytokine production. T lymphocytes stimulated with DCs pulsed with cell lysates of honokiol-treated tumour cells significantly increased specific killing of human cholangiocarcinoma cells compared to those associated with DCs pulsed with cell lysates of untreated cholangiocarcinoma cells. \r\n\r\n Conclusion: The present findings suggested that honokiol was able to enhance the immunogenicity of cholangiocarcinoma cells associated with increased effectiveness of DC-based vaccine formulation. Treatment of tumour cells with honokiol offers a promising approach as an ex vivo DC-based anticancer vaccine. STN","prediction_labels":"ANIMAL"},{"cleaned":"survival benefit adjuvant chemoradiotherapy patients ampulla vater cancer systematic review meta analysis objective conducted systematic review meta analysis focusing impact adjuvant radiotherapy rt overall survival os ampulla vater aov cancer background adjuvant treatment aov cancer subject controversy without convincing evidence randomized study methods comprehensive search performed databases embase pubmed web science cochrane library ovid inception july 2014 included studies compared survival patients without adjuvant rt curative surgery solely aov cancer hazard ratio hr os extracted random effects model used pooled analysis results ten retrospective studies including 3361 patients met inclusion criteria included final meta analysis adjuvant rt delivered concurrent chemotherapy mostly 5 fluorouracil institutional studies generally adjuvant rt groups included patients locally advanced disease lymph node metastasis surgery alone groups pooled results demonstrated adjuvant rt significantly reduced risk death hr 0 75 p 0 01 exploratory analyses showed patients lymph node metastasis hr 0 52 p 0 001 locally advanced disease hr 0 42 p 0 001 may also survival benefit adjuvant rt clear evidence publication bias found conclusions first meta analysis evaluating role adjuvant rt aov cancer results suggest potential survival benefit adjuvant chemoradiotherapy studies preferably randomized clinical trials needed confirm results pubmed","probabilities":0.9799733,"Title":"Survival Benefit of Adjuvant Chemoradiotherapy in Patients With Ampulla of Vater Cancer: A Systematic Review and Meta-analysis","Abstract":"OBJECTIVE: We conducted a systematic review and meta-analysis focusing on the impact of adjuvant radiotherapy (RT) on overall survival (OS) in ampulla of Vater (AoV) cancer. BACKGROUND: The adjuvant treatment for AoV cancer is a subject of controversy without convincing evidence from randomized study. METHODS: A comprehensive search was performed in the databases of EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to July 2014. We included studies, which compared survival between patients with or without adjuvant RT after curative surgery solely for AoV cancer. Hazard ratio (HR) for OS was extracted, and a random-effects model was used for pooled analysis. RESULTS: Ten retrospective studies including 3361 patients met all inclusion criteria and were included for the final meta-analysis. Adjuvant RT was delivered with concurrent chemotherapy, mostly 5-fluorouracil, in all institutional studies. Generally, adjuvant RT groups included more patients with locally advanced disease or lymph node metastasis than did the surgery alone groups. The pooled results demonstrated that adjuvant RT significantly reduced the risk of death (HR = 0.75; P = 0.01). Exploratory analyses showed that patients with lymph node metastasis (HR = 0.52; P = 0.001) and locally advanced disease (HR = 0.42; P = 0.001) may also have survival benefit from adjuvant RT. No clear evidence of publication bias was found. CONCLUSIONS: This is the first meta-analysis evaluating the role of adjuvant RT in AoV cancer. Our results suggest the potential for survival benefit of adjuvant chemoradiotherapy. Further studies, preferably randomized clinical trials, are needed to confirm our results.","Source":"PubMed","category":"HUMAN","training_data":"Survival Benefit of Adjuvant Chemoradiotherapy in Patients With Ampulla of Vater Cancer: A Systematic Review and Meta-analysis OBJECTIVE: We conducted a systematic review and meta-analysis focusing on the impact of adjuvant radiotherapy (RT) on overall survival (OS) in ampulla of Vater (AoV) cancer. BACKGROUND: The adjuvant treatment for AoV cancer is a subject of controversy without convincing evidence from randomized study. METHODS: A comprehensive search was performed in the databases of EMBASE, PubMed, Web of Science, Cochrane Library, and Ovid from inception to July 2014. We included studies, which compared survival between patients with or without adjuvant RT after curative surgery solely for AoV cancer. Hazard ratio (HR) for OS was extracted, and a random-effects model was used for pooled analysis. RESULTS: Ten retrospective studies including 3361 patients met all inclusion criteria and were included for the final meta-analysis. Adjuvant RT was delivered with concurrent chemotherapy, mostly 5-fluorouracil, in all institutional studies. Generally, adjuvant RT groups included more patients with locally advanced disease or lymph node metastasis than did the surgery alone groups. The pooled results demonstrated that adjuvant RT significantly reduced the risk of death (HR = 0.75; P = 0.01). Exploratory analyses showed that patients with lymph node metastasis (HR = 0.52; P = 0.001) and locally advanced disease (HR = 0.42; P = 0.001) may also have survival benefit from adjuvant RT. No clear evidence of publication bias was found. CONCLUSIONS: This is the first meta-analysis evaluating the role of adjuvant RT in AoV cancer. Our results suggest the potential for survival benefit of adjuvant chemoradiotherapy. Further studies, preferably randomized clinical trials, are needed to confirm our results. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic analysis radical resection intrahepatic cholangiocarcinoma retrospective cohort study aim study investigate relationship clinicopathological characteristics intrahepatic cholangiocarcinoma icc disease free survival dfs overall survival os intrahepatic cholangiocarcinoma icc patients underwent radical resection r0 retrospectively analyzed clinicopathological characteristics 319 patients underwent radical resection icc october 1999 december 2003 independent adverse prognostic factors affected dfs radical resection icc follows maximum tumor diameter hr 1 330 p 0 014 complicated bile duct stone hr 1 923 p 0 013 macroscopic tumor thrombus hr 1 826 p 0 009 lymph node metastasis pathology n1 hr 2 330 p 0 005 independent adverse prognostic factors affected dfs radical resection icc postoperative median dfs 6 months independent adverse prognostic factors affected os radical resection icc follows maximum tumor diameter hr 1 326 p 0 014 complicated bile duct stone hr 2 349 p 0 001 lymph node metastasis pathology n1 hr 2 420 p 0 003 postoperative median survival time 22 months 3 year survival rate 33 9 5 year survival rate 23 2 macroscopic tumor thrombus 2 991 p 0 004 independent risk factor death within 1 year radical resection stn","probabilities":0.9799733,"Title":"Prognostic Analysis Of Radical Resection For Intrahepatic Cholangiocarcinoma: A Retrospective Cohort Study","Abstract":"The aim of this study was to investigate the relationship between the clinicopathological characteristics of intrahepatic cholangiocarcinoma (ICC) and both disease-free survival (DFS) and overall survival (OS) in intrahepatic cholangiocarcinoma (ICC) patients who underwent radical resection (R0). We retrospectively analyzed the clinicopathological characteristics of 319 patients who underwent radical resection of ICC between October 1999 and December 2003. The independent adverse prognostic factors that affected DFS after radical resection of ICC were as follows: maximum tumor diameter (HR = 1.330, P = 0.014), complicated bile duct stone (HR = 1.923, P = 0.013), macroscopic tumor thrombus (HR = 1.826, P = 0.009), and lymph node metastasis (Pathology N1) (HR = 2.330, P = 0.005) were independent adverse prognostic factors that affected the DFS after radical resection of ICC. The postoperative median DFS was 6 months. The independent adverse prognostic factors that affected OS after radical resection of ICC were as follows: maximum tumor diameter (HR = 1.326, P = 0.014), complicated bile duct stone (HR = 2.349, P = 0.001), and lymph node metastasis (Pathology N1) (HR = 2.420, P = 0.003). The postoperative median survival time was 22 months, the 3-year survival rate was 33.9%, and the 5-year survival rate was 23.2%. Macroscopic tumor thrombus (OR = 2.991, P = 0.004) was an independent risk factor for death within 1 year after radical resection.","Source":"STN","category":"HUMAN","training_data":"Prognostic Analysis Of Radical Resection For Intrahepatic Cholangiocarcinoma: A Retrospective Cohort Study The aim of this study was to investigate the relationship between the clinicopathological characteristics of intrahepatic cholangiocarcinoma (ICC) and both disease-free survival (DFS) and overall survival (OS) in intrahepatic cholangiocarcinoma (ICC) patients who underwent radical resection (R0). We retrospectively analyzed the clinicopathological characteristics of 319 patients who underwent radical resection of ICC between October 1999 and December 2003. The independent adverse prognostic factors that affected DFS after radical resection of ICC were as follows: maximum tumor diameter (HR = 1.330, P = 0.014), complicated bile duct stone (HR = 1.923, P = 0.013), macroscopic tumor thrombus (HR = 1.826, P = 0.009), and lymph node metastasis (Pathology N1) (HR = 2.330, P = 0.005) were independent adverse prognostic factors that affected the DFS after radical resection of ICC. The postoperative median DFS was 6 months. The independent adverse prognostic factors that affected OS after radical resection of ICC were as follows: maximum tumor diameter (HR = 1.326, P = 0.014), complicated bile duct stone (HR = 2.349, P = 0.001), and lymph node metastasis (Pathology N1) (HR = 2.420, P = 0.003). The postoperative median survival time was 22 months, the 3-year survival rate was 33.9%, and the 5-year survival rate was 23.2%. Macroscopic tumor thrombus (OR = 2.991, P = 0.004) was an independent risk factor for death within 1 year after radical resection. STN","prediction_labels":"HUMAN"},{"cleaned":"risk estimation biliary tract cancer development validation prognostic score background aims biliary tract cancer rare tumour entity characterized poor prognosis aimed identify prognostic factors create prognostic score estimate survival methods clinical data training set consisting 569 patients treated 2000 2010 hannover medical school analysed prognostic model defining three prognostic risk groups derived cox regression analyses score applied validated independent cohort 557 patients four different german centres results median overall survival os 14 5 months complete resection performed patients significantly improved os 23 9 months n 242 compared patients non resectable tumours 9 1 months n 329 p 0001 based univariable multivariable analyses clinical data prognostic model created using variables available treatment age metastasis c reactive protein crp international normalized ratio inr bilirubin prognostic score distinguished three groups median os 21 8 8 6 2 6 months respectively validation cohort median os 20 2 14 0 6 5 months respectively prognostic impact score independent tumour site treatment procedures conclusions identified prognostic factors propose prognostic score estimate survival applied patients independent tumour site initial treatment validation prospective trials required pubmed","probabilities":0.9799733,"Title":"Risk estimation for biliary tract cancer: Development and validation of a prognostic score","Abstract":"BACKGROUND & AIMS: Biliary tract cancer is a rare tumour entity characterized by a poor prognosis. We aimed to identify prognostic factors and create a prognostic score to estimate survival. METHODS: Clinical data of the training set, consisting of 569 patients treated from 2000 to 2010 at Hannover Medical School, were analysed. A prognostic model defining three prognostic risk groups was derived from Cox regression analyses. The score was applied and validated in an independent cohort of 557 patients from four different German centres. RESULTS: Median overall survival (OS) was 14.5 months. If complete resection was performed, the patients had a significantly improved OS (23.9 months; n=242) as compared to patients with non-resectable tumours (9.1 months; n=329, P<.0001). Based on univariable and multivariable analyses of clinical data, a prognostic model was created using variables available before treatment. Those were age, metastasis, C-reactive protein (CRP), international normalized ratio (INR) and bilirubin. The prognostic score distinguished three groups with a median OS of 21.8, 8.6 and 2.6 months respectively. The validation cohort had a median OS of 20.2, 14.0 and 6.5 months respectively. The prognostic impact of the score was independent of the tumour site and of treatment procedures. CONCLUSIONS: Here, we identified prognostic factors and propose a prognostic score to estimate survival, which can be applied to all patients independent of tumour site and before initial treatment. Further validation in prospective trials is required.","Source":"PubMed","category":"HUMAN","training_data":"Risk estimation for biliary tract cancer: Development and validation of a prognostic score BACKGROUND & AIMS: Biliary tract cancer is a rare tumour entity characterized by a poor prognosis. We aimed to identify prognostic factors and create a prognostic score to estimate survival. METHODS: Clinical data of the training set, consisting of 569 patients treated from 2000 to 2010 at Hannover Medical School, were analysed. A prognostic model defining three prognostic risk groups was derived from Cox regression analyses. The score was applied and validated in an independent cohort of 557 patients from four different German centres. RESULTS: Median overall survival (OS) was 14.5 months. If complete resection was performed, the patients had a significantly improved OS (23.9 months; n=242) as compared to patients with non-resectable tumours (9.1 months; n=329, P<.0001). Based on univariable and multivariable analyses of clinical data, a prognostic model was created using variables available before treatment. Those were age, metastasis, C-reactive protein (CRP), international normalized ratio (INR) and bilirubin. The prognostic score distinguished three groups with a median OS of 21.8, 8.6 and 2.6 months respectively. The validation cohort had a median OS of 20.2, 14.0 and 6.5 months respectively. The prognostic impact of the score was independent of the tumour site and of treatment procedures. CONCLUSIONS: Here, we identified prognostic factors and propose a prognostic score to estimate survival, which can be applied to all patients independent of tumour site and before initial treatment. Further validation in prospective trials is required. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological features long term survivors advanced biliary tract cancer impact number lymph nodes involved background aim investigate characteristics long term survivors surgery advanced biliary tract cancer btc especially local invasion lymph node involvement methods analyzed features long term survivors using prospectively collected database verified results using recent patients data well described especially relation lymph node dissection metastasis used classification japanese society biliary surgery jsbs results among 170 patients advanced btc stage iii iv jsbs 25 10 bile duct cancer 9 gall bladder cancer 6 cancer papilla vater survived 5 years twenty four patients undergone fcura b r0 surgery 25 patients comparison patients survive 5 years long term survivors fewer metastatic lymph nodes three p 0 0028 regard impact lymph node metastasis prognostic factor number lymph nodes 3 year overall survival 0 1 68 1 vs 2 40 0 p 0 0304 conclusion obtaining long term survival curative resection necessary patients one lymph node metastasis pubmed","probabilities":0.9799733,"Title":"Clinicopathological features of long-term survivors for advanced biliary tract cancer and impact of the number of lymph nodes involved","Abstract":"BACKGROUND & AIM: To investigate the characteristics of long-term survivors after surgery for advanced biliary tract cancer (BTC), especially those with local invasion and/or lymph node involvement. METHODS: We analyzed the features of long-term survivors using a prospectively collected database and verified the results using recent patients' data which have been well-described, especially in relation to lymph node dissection and metastasis. We used classification by the Japanese Society of Biliary Surgery (JSBS). RESULTS: Among 170 patients with advanced BTC (Stage III or IV in JSBS), 25 (10 bile duct cancer, 9 gall bladder cancer, and 6 cancer of the papilla of Vater) survived for more than 5 years. Twenty-four patients had undergone fCurA/B (R0) surgery in these 25 patients. In comparison with the patients who did not survive for 5 years, the long-term survivors had fewer metastatic lymph nodes, that is, up to three (p = 0.0028). In regard to the impact of lymph node metastasis, the prognostic factor was the number of lymph nodes (3-year overall survival, 0 or 1: 68.1% vs >2: 40.0%, p = 0.0304). CONCLUSION: For obtaining long-term survival, curative resection would be necessary in patients with no more than one lymph node metastasis.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological features of long-term survivors for advanced biliary tract cancer and impact of the number of lymph nodes involved BACKGROUND & AIM: To investigate the characteristics of long-term survivors after surgery for advanced biliary tract cancer (BTC), especially those with local invasion and/or lymph node involvement. METHODS: We analyzed the features of long-term survivors using a prospectively collected database and verified the results using recent patients' data which have been well-described, especially in relation to lymph node dissection and metastasis. We used classification by the Japanese Society of Biliary Surgery (JSBS). RESULTS: Among 170 patients with advanced BTC (Stage III or IV in JSBS), 25 (10 bile duct cancer, 9 gall bladder cancer, and 6 cancer of the papilla of Vater) survived for more than 5 years. Twenty-four patients had undergone fCurA/B (R0) surgery in these 25 patients. In comparison with the patients who did not survive for 5 years, the long-term survivors had fewer metastatic lymph nodes, that is, up to three (p = 0.0028). In regard to the impact of lymph node metastasis, the prognostic factor was the number of lymph nodes (3-year overall survival, 0 or 1: 68.1% vs >2: 40.0%, p = 0.0304). CONCLUSION: For obtaining long-term survival, curative resection would be necessary in patients with no more than one lymph node metastasis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparative effectiveness hepatic artery based therapies unresectable intrahepatic cholangiocarcinoma background hepatic artery based therapies hat offered patients unresectable intrahepatic cholangiocarcinoma icc aimed evaluate comparative effectiveness hat hepatic arterial infusion hai transcatheter arterial chemoembolization tace drug eluting bead tace deb tace yttrium 90 radioembolization y 90 unresectable icc methods meta analysis performed using prospectively registered search strategy prospero crd42013004830 utilized pubmed 2003 2013 primary outcome median overall survival os secondary outcomes tumor response therapy toxicity results total 20 articles 793 n 657 patients selected data extraction highest median os observed hai 22 8 95 ci 9 8 35 8 months versus y90 13 9 9 5 18 3 months versus tace 12 4 10 9 13 9 months versus deb tace 12 3 11 13 5 months response therapy complete partial highest hai 56 9 95 ci 41 0 72 8 versus y90 27 4 17 4 37 5 versus tace 17 3 6 8 27 8 grade iii iv toxicity events per patient highest hai 0 35 95 ci 0 22 0 48 versus tace 0 26 0 21 0 32 versus deb tace 0 32 0 17 0 48 conclusion patients unresectable icc treated hat hai offered best outcomes terms tumor response survival may limited toxicity pubmed","probabilities":0.9799733,"Title":"Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Hepatic artery based therapies (HAT) are offered for patients with unresectable intrahepatic cholangiocarcinoma (ICC). We aimed to evaluate the comparative effectiveness of HAT -hepatic arterial infusion (HAI), transcatheter arterial chemoembolization (TACE), drug-eluting bead TACE (DEB-TACE), and Yttrium(90) radioembolization (Y-90) for unresectable ICC. METHODS: A meta-analysis was performed using a prospectively registered search strategy at PROSPERO (CRD42013004830) that utilized PubMed (2003-2013). Primary outcome was median overall survival (OS), and secondary outcomes were tumor response to therapy and toxicity. RESULTS: A total of 20 articles (of 793, n=657 patients) were selected for data extraction. Highest Median OS was observed for HAI (22.8, 95% CI 9.8-35.8) months versus Y90 (13.9, 9.5-18.3) months versus TACE (12.4, 10.9-13.9) months versus DEB-TACE (12.3, 11-13.5) months. Response to therapy (complete and partial) was highest for HAI (56.9%, 95%CI 41.0-72.8) versus Y90 (27.4%, 17.4-37.5) versus TACE (17.3%, 6.8-27.8). The grade III/IV toxicity (Events per patient) was highest for HAI (0.35, 95% CI 0.22-0.48) versus TACE (0.26, 0.21-0.32) versus DEB-TACE (0.32, 0.17-0.48). CONCLUSION: For patients with unresectable ICC treated with HAT, HAI offered the best outcomes in terms of tumor response and survival but may be limited by toxicity.","Source":"PubMed","category":"HUMAN","training_data":"Comparative effectiveness of hepatic artery based therapies for unresectable intrahepatic cholangiocarcinoma BACKGROUND: Hepatic artery based therapies (HAT) are offered for patients with unresectable intrahepatic cholangiocarcinoma (ICC). We aimed to evaluate the comparative effectiveness of HAT -hepatic arterial infusion (HAI), transcatheter arterial chemoembolization (TACE), drug-eluting bead TACE (DEB-TACE), and Yttrium(90) radioembolization (Y-90) for unresectable ICC. METHODS: A meta-analysis was performed using a prospectively registered search strategy at PROSPERO (CRD42013004830) that utilized PubMed (2003-2013). Primary outcome was median overall survival (OS), and secondary outcomes were tumor response to therapy and toxicity. RESULTS: A total of 20 articles (of 793, n=657 patients) were selected for data extraction. Highest Median OS was observed for HAI (22.8, 95% CI 9.8-35.8) months versus Y90 (13.9, 9.5-18.3) months versus TACE (12.4, 10.9-13.9) months versus DEB-TACE (12.3, 11-13.5) months. Response to therapy (complete and partial) was highest for HAI (56.9%, 95%CI 41.0-72.8) versus Y90 (27.4%, 17.4-37.5) versus TACE (17.3%, 6.8-27.8). The grade III/IV toxicity (Events per patient) was highest for HAI (0.35, 95% CI 0.22-0.48) versus TACE (0.26, 0.21-0.32) versus DEB-TACE (0.32, 0.17-0.48). CONCLUSION: For patients with unresectable ICC treated with HAT, HAI offered the best outcomes in terms of tumor response and survival but may be limited by toxicity. PubMed","prediction_labels":"HUMAN"},{"cleaned":"external beam radiation therapy without concurrent chemotherapy patients unresectable locally advanced hilar cholangiocarcinoma background aims evaluate efficacy concurrent chemoradiotherapy ccrt compared radiotherapy rt unresectable locally advanced hilar cholangiocarcinoma hcca methodology 2001 2010 34 patients unresectable locally advanced hcca institute reviewed eighteen patients received rt 16 patients received ccrt survivals multivariate analyses performed explore potential variables affecting survivals results 18 males 16 females median age 72 years median follow time 9 4 months median overall survival os 10 4 months 95 ci 6 7 13 5 1 year survival rates 41 median os progression free survival pfs 13 5 months 8 8 months patients receiving ccrt compared 6 7 months 4 4 months patients receiving rt alone p 0 003 p 0 005 respectively multivariate analysis demonstrated karnofsky performance status kps 80 p 0 001 pretreatment carbohydrate antigen 19 9 ca 19 9 200 u ml p 0 045 ccrt prognostic factors os pfs conclusions compared rt ccrt provides longer os pfs patients unresectable hcca efficacy adding novel chemotherapeutic rt needs investigated pubmed","probabilities":0.9799733,"Title":"External beam radiation therapy with or without concurrent chemotherapy for patients with unresectable locally advanced hilar cholangiocarcinoma","Abstract":"BACKGROUND/AIMS: To evaluate the efficacy of concurrent chemoradiotherapy (CCRT) compared to radiotherapy (RT) for unresectable, locally advanced hilar cholangiocarcinoma (HCCA). METHODOLOGY: Between 2001 and 2010, 34 patients with unresectable locally advanced HCCA at our institute were reviewed. Eighteen patients received RT and 16 patients received CCRT. Survivals and multivariate analyses were performed to explore potential variables affecting survivals. RESULTS: There were 18 males and 16 females, with a median age of 72 years and median follow-up time 9.4 months. The median overall survival (OS) was 10.4 months (95% CI, 6.7-13.5) with the 1-year survival rates of 41%. The median OS and progression-free survival (PFS) were 13.5 months and 8.8 months for patients receiving CCRT as compared to 6.7 months and 4.4 months for patients receiving RT alone (p = 0.003 and p = 0.005, respectively). On multivariate analysis demonstrated that Karnofsky performance status (KPS) ≥ 80 (p = 0.001), pretreatment carbohydrate antigen 19-9 (CA 19-9) 200 U/ml (p = 0.045) and CCRT were prognostic factors for OS and PFS. CONCLUSIONS: As compared with RT, CCRT provides longer OS and PFS for patients with unresectable HCCA. The efficacy of adding novel chemotherapeutic to RT needs to be further investigated.","Source":"PubMed","category":"HUMAN","training_data":"External beam radiation therapy with or without concurrent chemotherapy for patients with unresectable locally advanced hilar cholangiocarcinoma BACKGROUND/AIMS: To evaluate the efficacy of concurrent chemoradiotherapy (CCRT) compared to radiotherapy (RT) for unresectable, locally advanced hilar cholangiocarcinoma (HCCA). METHODOLOGY: Between 2001 and 2010, 34 patients with unresectable locally advanced HCCA at our institute were reviewed. Eighteen patients received RT and 16 patients received CCRT. Survivals and multivariate analyses were performed to explore potential variables affecting survivals. RESULTS: There were 18 males and 16 females, with a median age of 72 years and median follow-up time 9.4 months. The median overall survival (OS) was 10.4 months (95% CI, 6.7-13.5) with the 1-year survival rates of 41%. The median OS and progression-free survival (PFS) were 13.5 months and 8.8 months for patients receiving CCRT as compared to 6.7 months and 4.4 months for patients receiving RT alone (p = 0.003 and p = 0.005, respectively). On multivariate analysis demonstrated that Karnofsky performance status (KPS) ≥ 80 (p = 0.001), pretreatment carbohydrate antigen 19-9 (CA 19-9) 200 U/ml (p = 0.045) and CCRT were prognostic factors for OS and PFS. CONCLUSIONS: As compared with RT, CCRT provides longer OS and PFS for patients with unresectable HCCA. The efficacy of adding novel chemotherapeutic to RT needs to be further investigated. PubMed","prediction_labels":"HUMAN"},{"cleaned":"high mobility group box 1 expression predicts survival patients resection adenocarcinoma ampulla vater background expression high mobility group box 1 hmgb1 multifunctional protein involved dna function well cell proliferation inflammation immune response reported prognostic several types malignancies however prognostic value hmgb1 ampullary cancer studied methods patients adenocarcinoma ampulla vater underwent r0 resection pancreaticoduodenectomy 2001 2011 included present multi institutional study degree hmgb1 expression examined resected specimen immunohistochemical staining results total 101 patients enrolled 79 patients eligible high expression hmgb1 observed 31 39 patients blood loss transfusion tumor stage nodal status hmgb1 expression identified predictors univariate analysis multivariate analysis showed transfusion lymph node metastasis high hmgb1 expression independent predictors poor overall survival subgroup analysis showed high hmgb1 expression predictive especially patients receive adjuvant chemotherapy conclusions high hmgb1 expression independent predictor poor prognosis patients adenocarcinoma ampulla vater treated adjuvant chemotherapy pubmed","probabilities":0.962963,"Title":"High-Mobility Group Box 1 expression predicts survival of patients after resection of adenocarcinoma of the ampulla of Vater","Abstract":"BACKGROUND: Expression of High-Mobility Group Box 1 (HMGB1), a multifunctional protein involved in DNA function as well as cell proliferation, inflammation, and the immune response, has been reported to be prognostic in several types of malignancies. However, the prognostic value of HMGB1 in ampullary cancer has not been studied. METHODS: Patients with adenocarcinoma of the ampulla of Vater who underwent R0 resection with pancreaticoduodenectomy between 2001 and 2011 were included in the present multi-institutional study. The degree of HMGB1 expression was examined in each resected specimen by immunohistochemical staining. RESULTS: A total of 101 patients were enrolled of which, 79 patients were eligible. High expression of HMGB1 was observed in 31 (39%) patients. Blood loss, transfusion, tumor stage, nodal status, and HMGB1 expression were identified as predictors with univariate analysis. Multivariate analysis showed that transfusion, lymph-node metastasis, and high HMGB1 expression were independent predictors of poor overall survival. Subgroup analysis showed that high HMGB1 expression was predictive, especially in patients who did not receive adjuvant chemotherapy. CONCLUSIONS: High HMGB1 expression is an independent predictor of poor prognosis in patients with adenocarcinoma of the ampulla of Vater not treated with adjuvant chemotherapy.","Source":"PubMed","category":"HUMAN","training_data":"High-Mobility Group Box 1 expression predicts survival of patients after resection of adenocarcinoma of the ampulla of Vater BACKGROUND: Expression of High-Mobility Group Box 1 (HMGB1), a multifunctional protein involved in DNA function as well as cell proliferation, inflammation, and the immune response, has been reported to be prognostic in several types of malignancies. However, the prognostic value of HMGB1 in ampullary cancer has not been studied. METHODS: Patients with adenocarcinoma of the ampulla of Vater who underwent R0 resection with pancreaticoduodenectomy between 2001 and 2011 were included in the present multi-institutional study. The degree of HMGB1 expression was examined in each resected specimen by immunohistochemical staining. RESULTS: A total of 101 patients were enrolled of which, 79 patients were eligible. High expression of HMGB1 was observed in 31 (39%) patients. Blood loss, transfusion, tumor stage, nodal status, and HMGB1 expression were identified as predictors with univariate analysis. Multivariate analysis showed that transfusion, lymph-node metastasis, and high HMGB1 expression were independent predictors of poor overall survival. Subgroup analysis showed that high HMGB1 expression was predictive, especially in patients who did not receive adjuvant chemotherapy. CONCLUSIONS: High HMGB1 expression is an independent predictor of poor prognosis in patients with adenocarcinoma of the ampulla of Vater not treated with adjuvant chemotherapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder cancer 16 years cerrahpasa experience introduction incidence gallbladder cancer 0 3 1 5 incidence incidental gallbladder cancer 0 19 3 3 five year survival 505 t1 tumors 29 t2 tumors puropose study present experience incidental gallbladder cancer patients operated cholelithiasis method patients operated cholelithiasis january 1999 2015 included study incidental gallbladder cancer investigated retrospectively exclusion criteria preoperative suspicion malignancy gallbladder polyps result 16 years 4851 cholecystectomies performed 4192 86 4 wer finished laproscopically incidental gallbladder cancer detected 19 0 39 fourteen 73 9 female five 26 3 male mean age 69 5 13 4 40 90 years eight 19 patients 42 1 converted laprotomy distribution tumor stages according american joint committee cancer one situ cancer one t1 four t2 twelve t3 pathological diagnosis 13 adenocarcinomas two neuroendocrine tumors two mucinous carcinomas one adenosquamours carcinoma one situ cancer postoperative mean survival 20 5 41 5 1 180 months two t3 wedge resection gallbladder bed regional lymph node dissection performed adjuvant chemotherapy administered 7 36 8 patients mean survey 13 3 11 9 months t2 9 7 16 5 months t3 addition survey situ cancer patient 180 months t1 patient 30 months patients still disease free conclusion subclinical malignancies end poor result gallbladder specimens exaimed histopathologically strongly suggest routine histopathological examination cholecystectomy specimens google scholar","probabilities":0.9799733,"Title":"Incidental Gallbladder Cancer: 16 Years Cerrahpasa Experience","Abstract":"Introduction: While incidence of gallbladder cancer is 0.3-1.5%, incidence of incidental gallbladder cancer is 0.19-3.3%. Five-year survival is 505 for T1 tumors and 29% for T2 tumors. Puropose of this study is to present experience in incidental gallbladder cancer in patients operated for cholelithiasis\nMethod(s): Patients who were operated with cholelithiasis between January 1999-2015 where included to study and incidental gallbladder cancer were investigated retrospectively. Exclusion criteria was preoperative suspicion for malignancy and gallbladder polyps.\nResult(s): In 16 years, 4851, cholecystectomies were performed. Of them, 4192 (86.4%) wer finished laproscopically. Incidental gallbladder cancer was detected in 19(0.39%). Fourteen (73.9%) of them were female and five (26.3%) were male. Mean age was 69.5+/-13.4 (40-90) years. EIght of 19 patients (42.1%) were converted to laprotomy. Distribution of tumor stages according to American Joint Committee of cancer was one in situ cancer, one T1, four T2, twelve T3. Pathological diagnosis were 13 adenocarcinomas, two neuroendocrine tumors, two mucinous carcinomas, one adenosquamours carcinoma, and one in situ cancer. Postoperative mean survival was 20.5 +/- 41.5 (1-180) months. In two T3, wedge resection of gallbladder bed and regional lymph node dissection was performed. Adjuvant chemotherapy was administered to 7(36.8%) patients. Mean survey was 13.3+/-11.9 months in T2 and 9.7 +/- 16.5 months in T3. In addition, survey of the in situ cancer patient was 180 months, the T1 patient was 30 months, and both patients are still disease free.\nConclusion: Subclinical malignancies can end up with poor result if not all gallbladder specimens are exaimed histopathologically. We strongly suggest routine histopathological examination of cholecystectomy specimens.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidental Gallbladder Cancer: 16 Years Cerrahpasa Experience Introduction: While incidence of gallbladder cancer is 0.3-1.5%, incidence of incidental gallbladder cancer is 0.19-3.3%. Five-year survival is 505 for T1 tumors and 29% for T2 tumors. Puropose of this study is to present experience in incidental gallbladder cancer in patients operated for cholelithiasis\nMethod(s): Patients who were operated with cholelithiasis between January 1999-2015 where included to study and incidental gallbladder cancer were investigated retrospectively. Exclusion criteria was preoperative suspicion for malignancy and gallbladder polyps.\nResult(s): In 16 years, 4851, cholecystectomies were performed. Of them, 4192 (86.4%) wer finished laproscopically. Incidental gallbladder cancer was detected in 19(0.39%). Fourteen (73.9%) of them were female and five (26.3%) were male. Mean age was 69.5+/-13.4 (40-90) years. EIght of 19 patients (42.1%) were converted to laprotomy. Distribution of tumor stages according to American Joint Committee of cancer was one in situ cancer, one T1, four T2, twelve T3. Pathological diagnosis were 13 adenocarcinomas, two neuroendocrine tumors, two mucinous carcinomas, one adenosquamours carcinoma, and one in situ cancer. Postoperative mean survival was 20.5 +/- 41.5 (1-180) months. In two T3, wedge resection of gallbladder bed and regional lymph node dissection was performed. Adjuvant chemotherapy was administered to 7(36.8%) patients. Mean survey was 13.3+/-11.9 months in T2 and 9.7 +/- 16.5 months in T3. In addition, survey of the in situ cancer patient was 180 months, the T1 patient was 30 months, and both patients are still disease free.\nConclusion: Subclinical malignancies can end up with poor result if not all gallbladder specimens are exaimed histopathologically. We strongly suggest routine histopathological examination of cholecystectomy specimens. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cancer survival eastern western germany fall iron curtain prior german reunification cancer survival much lower east west germany compare cancer survival eastern western germany early twenty first century e second decade german reunification using data 11 population based cancer registries covering population 33 million people 5 year age standardized relative survival time period 2002 2006 estimated 25 common cancers using model based period analysis 2002 2006 5 year relative survival similar cancers differences 3 units 20 25 cancer sites larger statistically significant survival advantages seen oral cavity oesophagus gallbladder cancer skin melanoma west leukemia east study shows within two decades assimilation political health care systems former major survival gap cancer patients eastern germany essentially overcome result encouraging suggests even though economic conditions remained difficult eastern germany comparable health care provision may nevertheless enable comparable levels cancer survival within relatively short period time stn","probabilities":0.9799733,"Title":"Cancer Survival In Eastern And Western Germany After The Fall Of The Iron Curtain","Abstract":"Prior to the German reunification, cancer survival was much lower in East than in West Germany. We compare cancer survival between Eastern and Western Germany in the early twenty-first century, i.e. the second decade after the German reunification. Using data from 11 population-based cancer registries covering a population of 33 million people, 5-year age-standardized relative survival for the time period 2002-2006 was estimated for the 25 most common cancers using model-based period analysis. In 2002-2006, 5-year relative survival was very similar for most cancers, with differences below 3% units for 20 of 25 cancer sites. Larger, statistically significant survival advantages were seen for oral cavity, oesophagus, and gallbladder cancer and skin melanoma in the West and for leukemia in the East. Our study shows that within two decades after the assimilation of political and health care systems, the former major survival gap of cancer patients in Eastern Germany has been essentially overcome. This result is encouraging as it suggests that, even though economic conditions have remained difficult in Eastern Germany, comparable health care provision may nevertheless enable comparable levels of cancer survival within a relatively short period of time.","Source":"STN","category":"HUMAN","training_data":"Cancer Survival In Eastern And Western Germany After The Fall Of The Iron Curtain Prior to the German reunification, cancer survival was much lower in East than in West Germany. We compare cancer survival between Eastern and Western Germany in the early twenty-first century, i.e. the second decade after the German reunification. Using data from 11 population-based cancer registries covering a population of 33 million people, 5-year age-standardized relative survival for the time period 2002-2006 was estimated for the 25 most common cancers using model-based period analysis. In 2002-2006, 5-year relative survival was very similar for most cancers, with differences below 3% units for 20 of 25 cancer sites. Larger, statistically significant survival advantages were seen for oral cavity, oesophagus, and gallbladder cancer and skin melanoma in the West and for leukemia in the East. Our study shows that within two decades after the assimilation of political and health care systems, the former major survival gap of cancer patients in Eastern Germany has been essentially overcome. This result is encouraging as it suggests that, even though economic conditions have remained difficult in Eastern Germany, comparable health care provision may nevertheless enable comparable levels of cancer survival within a relatively short period of time. STN","prediction_labels":"HUMAN"},{"cleaned":"aso author reflections survival benefit adjuvant chemoradiotherapy gallbladder cancer role radiation therapy revisited past gallbladder cancer gbc rare highly aggressive malignancy even radical resection locoregional recurrence signi cant cause mortality gbc role adjuvant radiotherapy art still debated tends underestimated 1 impact adjuvant chemotherapy still remains controversial recently several retrospective studies based large database surveillance epidemiology end results national cancer database showed survival bene adjuvant radio chemo therapy supported need integrate art treatment strategies unfortunately well designed prospective randomized trial provide solid evidence available near future practice guidelines including national comprehensive cancer network nccn guideline provide clear answer adjuvant treatment decision making therefore overcome past limitations individual studies systematic review meta analysis performed explore survival bene art gbc 2 present study rst meta analysis evaluate role art mainly combined concurrent chemotherapy verify art may offer survival bene compared surgery alone pooled analysis 14 studies including 9364 patients showed art signi cantly reduced risk death hazard ratio hr 0 54 95 con dence interval ci 0 44 0 67 p 0 001 risk recurrence hr 0 61 95 ci 0 38 0 98 p 0 04 subgroup analysis found patients nodal involvement hr 0 61 r1 resection hr 0 55 likely bene art whereas patients without nodal diseases may bene although direct comparison adjuvant chemoradiotherapy adjuvant chemotherapy possible ndings analysis suggested adjuvant chemoradiotherapy also regarded viable adjuvant treatment option patients resected gbc google scholar","probabilities":0.9799733,"Title":"Aso Author Reflections: Survival Benefit Of Adjuvant Chemoradiotherapy For Gallbladder Cancer: The Role Of Radiation Therapy Revisited","Abstract":"PAST\nGallbladder cancer (GBC) is a rare but highly aggressive malignancy even after radical resection. Locoregional recurrence is a significant cause of mortality in GBC, but the role of adjuvant radiotherapy (ART) is still debated and tends to be underestimated.1 The impact of adjuvant chemotherapy still remains controversial. Recently, several retrospective studies based on a large database (The Surveillance, Epidemiology, and End Results or National Cancer Database) showed the survival benefit of adjuvant radio(chemo)therapy and supported the need to integrate ART into treatment strategies. Unfortunately, a well-designed prospective randomized trial to provide solid evidence would not be available in near future. Practice guidelines, including the National Comprehensive Cancer Network (NCCN) guideline, do not provide a clear answer to adjuvant treatment decision making. Therefore, to overcome past limitations of individual studies, a systematic review and meta-analysis was performed to explore the survival benefit of ART in GBC.2\nPRESENT\nThis study is the first meta-analysis to evaluate the role of ART (mainly combined with concurrent chemotherapy) and verify that ART may offer a survival benefit compared with surgery alone. A pooled analysis of 14 studies including 9364 patients showed that ART significantly reduced both the risk of death (hazard ratio [HR] 0.54; 95% confidence interval [CI] 0.44–0.67; p\\0.001) and the risk of recurrence (HR 0.61; 95% CI 0.38–0.98; p = 0.04). A subgroup analysis found that patients with nodal involvement (HR 0.61) or R1 resection (HR 0.55) are likely to benefit most from ART, whereas patients without nodal diseases may not benefit. Although direct comparison of adjuvant chemoradiotherapy with adjuvant chemotherapy was not possible, the findings from this analysis suggested that adjuvant chemoradiotherapy also should be regarded as a viable adjuvant treatment option for patients with resected GBC.","Source":"Google Scholar","category":"HUMAN","training_data":"Aso Author Reflections: Survival Benefit Of Adjuvant Chemoradiotherapy For Gallbladder Cancer: The Role Of Radiation Therapy Revisited PAST\nGallbladder cancer (GBC) is a rare but highly aggressive malignancy even after radical resection. Locoregional recurrence is a significant cause of mortality in GBC, but the role of adjuvant radiotherapy (ART) is still debated and tends to be underestimated.1 The impact of adjuvant chemotherapy still remains controversial. Recently, several retrospective studies based on a large database (The Surveillance, Epidemiology, and End Results or National Cancer Database) showed the survival benefit of adjuvant radio(chemo)therapy and supported the need to integrate ART into treatment strategies. Unfortunately, a well-designed prospective randomized trial to provide solid evidence would not be available in near future. Practice guidelines, including the National Comprehensive Cancer Network (NCCN) guideline, do not provide a clear answer to adjuvant treatment decision making. Therefore, to overcome past limitations of individual studies, a systematic review and meta-analysis was performed to explore the survival benefit of ART in GBC.2\nPRESENT\nThis study is the first meta-analysis to evaluate the role of ART (mainly combined with concurrent chemotherapy) and verify that ART may offer a survival benefit compared with surgery alone. A pooled analysis of 14 studies including 9364 patients showed that ART significantly reduced both the risk of death (hazard ratio [HR] 0.54; 95% confidence interval [CI] 0.44–0.67; p\\0.001) and the risk of recurrence (HR 0.61; 95% CI 0.38–0.98; p = 0.04). A subgroup analysis found that patients with nodal involvement (HR 0.61) or R1 resection (HR 0.55) are likely to benefit most from ART, whereas patients without nodal diseases may not benefit. Although direct comparison of adjuvant chemoradiotherapy with adjuvant chemotherapy was not possible, the findings from this analysis suggested that adjuvant chemoradiotherapy also should be regarded as a viable adjuvant treatment option for patients with resected GBC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"evaluation modifying effects 12 dcp bop induced hepatobilliary pancreatic carcinogenesis hamsters abstract available google scholar","probabilities":0.9799733,"Title":"Evaluation Of The Modifying Effects Of 12-Dcp On Bop-Induced Hepatobilliary And Pancreatic Carcinogenesis In Hamsters","Abstract":"Abstract not available","Source":"Google Scholar","category":"ANIMAL","training_data":"Evaluation Of The Modifying Effects Of 12-Dcp On Bop-Induced Hepatobilliary And Pancreatic Carcinogenesis In Hamsters Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors patterns locoregional failure surgical resection patients cholangiocarcinoma without adjuvant radiation therapy optimal field design adjuvant radiation therapy purpose identify prognostic factors patterns local failure patients cholangiocarcinoma cca surgical resection absence adjuvant radiation optimal definition target volumes encompassing majority local recurrences methods materials chart review performed patients underwent resection primary cca intrahepatic hilar distal 1999 2014 local failure defined recurrence theoretical reasonable postoperative radiation volume includes cut surface liver biliary anastomosis hilum portal nodes celiac nodes peri pancreatic nodes gastro hepatic nodes retroperitoneal nodes patients received adjuvant radiation excluded results total 189 patients underwent surgical resection cca 145 patients sufficient follow median follow 41 6 months 95 confidence interval 35 4 48 7 months 145 cases 102 intrahepatic 43 hilar distal cca adjuvant chemotherapy given 38 cases 26 20 54 gemcitabine based eighty six patients 59 documented recurrence 44 51 locoregional component among patients recurrence 23 27 recurrence biliary anastomosis cut liver surface twenty eight patients 32 6 recurrence regional lymph nodes prevalent portal 16 3 retroperitoneal 17 4 lymph nodes univariable analysis identified tumor size vascular invasion presence satellites stage nodal status receipt chemotherapy significant prognostic factors overall recurrence among intrahepatic patients presence satellites stage 3 nx status remained statistically significant multivariable modeling conclusions areas highest risk locoregional recurrence surgical resection primary cca biliary anastomosis cut liver surface portal lymph nodes retroperitoneal lymph nodes although results need validated adjuvant radiation possibly cover areas maximize locoregional control pubmed","probabilities":0.9799733,"Title":"Prognostic Factors and Patterns of Locoregional Failure After Surgical Resection in Patients With Cholangiocarcinoma Without Adjuvant Radiation Therapy: Optimal Field Design for Adjuvant Radiation Therapy","Abstract":"PURPOSE: To identify prognostic factors and patterns of local failure in patients with cholangiocarcinoma (CCA), after surgical resection in the absence of adjuvant radiation, for optimal definition of target volumes encompassing the majority of local recurrences. METHODS AND MATERIALS: A chart review was performed in patients who underwent resection for primary CCA (intrahepatic, hilar, and distal) between 1999 and 2014. Local failure was defined as recurrence in a theoretical reasonable postoperative radiation volume. This includes the cut surface of liver, biliary anastomosis, hilum, portal nodes, celiac nodes, peri-pancreatic nodes, gastro-hepatic nodes, and retroperitoneal nodes. Patients who received adjuvant radiation were excluded. RESULTS: A total of 189 patients underwent surgical resection for CCA, of whom 145 patients had sufficient follow-up. Median follow-up was 41.6 months (95% confidence interval 35.4-48.7 months). Of the 145 cases, 102 were intrahepatic and 43 were hilar/distal CCA. Adjuvant chemotherapy was given in 38 cases (26%), of which 20 (54%) were gemcitabine-based. Eighty-six patients (59%) had a documented recurrence, of whom 44 (51%) had a locoregional component. Among patients who had a recurrence, 23 (27%) had a recurrence at the biliary anastomosis and/or cut liver surface. Twenty-eight patients (32.6%) had a recurrence in the regional lymph nodes, most prevalent in the portal (16.3%) and retroperitoneal (17.4%) lymph nodes. Univariable analysis identified tumor size, any vascular invasion, presence of satellites, stage/nodal status, and receipt of chemotherapy as significant prognostic factors of overall recurrence among intrahepatic patients. Presence of satellites, and stage 3/Nx status remained statistically significant in multivariable modeling. CONCLUSIONS: The areas at highest risk for locoregional recurrence after surgical resection for primary CCA are the biliary anastomosis/cut liver surface, portal lymph nodes, and retroperitoneal lymph nodes. Although these results need to be validated, adjuvant radiation should possibly cover these areas to maximize locoregional control.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Factors and Patterns of Locoregional Failure After Surgical Resection in Patients With Cholangiocarcinoma Without Adjuvant Radiation Therapy: Optimal Field Design for Adjuvant Radiation Therapy PURPOSE: To identify prognostic factors and patterns of local failure in patients with cholangiocarcinoma (CCA), after surgical resection in the absence of adjuvant radiation, for optimal definition of target volumes encompassing the majority of local recurrences. METHODS AND MATERIALS: A chart review was performed in patients who underwent resection for primary CCA (intrahepatic, hilar, and distal) between 1999 and 2014. Local failure was defined as recurrence in a theoretical reasonable postoperative radiation volume. This includes the cut surface of liver, biliary anastomosis, hilum, portal nodes, celiac nodes, peri-pancreatic nodes, gastro-hepatic nodes, and retroperitoneal nodes. Patients who received adjuvant radiation were excluded. RESULTS: A total of 189 patients underwent surgical resection for CCA, of whom 145 patients had sufficient follow-up. Median follow-up was 41.6 months (95% confidence interval 35.4-48.7 months). Of the 145 cases, 102 were intrahepatic and 43 were hilar/distal CCA. Adjuvant chemotherapy was given in 38 cases (26%), of which 20 (54%) were gemcitabine-based. Eighty-six patients (59%) had a documented recurrence, of whom 44 (51%) had a locoregional component. Among patients who had a recurrence, 23 (27%) had a recurrence at the biliary anastomosis and/or cut liver surface. Twenty-eight patients (32.6%) had a recurrence in the regional lymph nodes, most prevalent in the portal (16.3%) and retroperitoneal (17.4%) lymph nodes. Univariable analysis identified tumor size, any vascular invasion, presence of satellites, stage/nodal status, and receipt of chemotherapy as significant prognostic factors of overall recurrence among intrahepatic patients. Presence of satellites, and stage 3/Nx status remained statistically significant in multivariable modeling. CONCLUSIONS: The areas at highest risk for locoregional recurrence after surgical resection for primary CCA are the biliary anastomosis/cut liver surface, portal lymph nodes, and retroperitoneal lymph nodes. Although these results need to be validated, adjuvant radiation should possibly cover these areas to maximize locoregional control. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intraductal papillary mucinous neoplasms pancreas concurrent pancreatic periampullary neoplasms background intraductal papillary mucinous neoplasms ipmn reported associated concurrent distinct pancreatic ductal adenocarcinoma con pdac 8 range 4 10 resected branch duct bd lesions addition pancreatic ampullary tumors occasionally diagnosed ipmn patients undergoing pancreatic surgery objective study describe prevalence clinicopathologic characteristics prognosis ipmn concurrent pancreatic ampullary neoplasms especially con pdac methods combined databases pancreatic resections massachusetts general hospital negrar hospital italy analyzed patients diagnosed ipmn concurrent pancreatic ampullary neoplasms results 2762 patients underwent pancreatic surgery january 2000 december 2012 sixteen percent n 441 pathologically confirmed ipmn 11 n 50 different distinct synchronous pancreatic neoplasm majority 62 con pdac followed neuroendocrine neoplasms 10 ampullary carcinoma 10 less frequently mucinous 6 well serous cystic neoplasms 6 adenosquamous carcinoma 4 distal bile duct cancer 2 diagnosed among patients synchronous neoplasms 66 harbored bd ipmn 28 combined ipmn 6 main duct ipmn abdominal pain jaundice leading symptoms half patients conclusion ipmn mainly bd ipmn associated con pdac 7 patients account 62 concurrent pancreatic ampullary neoplasms synchronous neoplasms may found sporadically ipmn without suspected association stn","probabilities":0.9799733,"Title":"Intraductal Papillary Mucinous Neoplasms Of The Pancreas With Concurrent Pancreatic And Periampullary Neoplasms","Abstract":"Background: Intraductal papillary mucinous neoplasms (IPMN) have been reported to be associated with concurrent, distinct pancreatic ductal adenocarcinoma (con-PDAC) in about 8% (range, 4-10%) of resected branch duct (BD) lesions. In addition, other pancreatic and ampullary tumors are occasionally diagnosed with IPMN in patients undergoing pancreatic surgery. The objective of this study is to describe the prevalence, clinicopathologic characteristics and prognosis of IPMN with concurrent pancreatic and ampullary neoplasms, especially con-PDAC. \r\n\r\n Methods: The combined databases of pancreatic resections from the Massachusetts General Hospital and the Negrar Hospital, Italy, were analyzed for patients who had been diagnosed with IPMN and concurrent pancreatic or ampullary neoplasms. \r\n\r\n Results: 2762 patients underwent pancreatic surgery from January 2000 to December 2012. Sixteen percent (n = 441) had pathologically confirmed IPMN and 11% of these (n = 50) had a different distinct synchronous pancreatic neoplasm. The majority of these, 62%, were con-PDAC, followed by neuroendocrine neoplasms (10%) and ampullary carcinoma (10%). Less frequently, mucinous (6%) as well as serous cystic neoplasms (6%), adenosquamous carcinoma (4%) and distal bile duct cancer (2%) were diagnosed. Among all patients with synchronous neoplasms, 66% harbored BD-IPMN, 28% combined IPMN and 6% main duct IPMN. Abdominal pain and/or jaundice were the leading symptoms in half of patients. \r\n\r\n Conclusion: IPMN, mainly BD-IPMN, are associated with con-PDAC in about 7% of patients and account for 62% of all concurrent pancreatic/ampullary neoplasms. Other synchronous neoplasms may be found sporadically with IPMN without a suspected association.","Source":"STN","category":"HUMAN","training_data":"Intraductal Papillary Mucinous Neoplasms Of The Pancreas With Concurrent Pancreatic And Periampullary Neoplasms Background: Intraductal papillary mucinous neoplasms (IPMN) have been reported to be associated with concurrent, distinct pancreatic ductal adenocarcinoma (con-PDAC) in about 8% (range, 4-10%) of resected branch duct (BD) lesions. In addition, other pancreatic and ampullary tumors are occasionally diagnosed with IPMN in patients undergoing pancreatic surgery. The objective of this study is to describe the prevalence, clinicopathologic characteristics and prognosis of IPMN with concurrent pancreatic and ampullary neoplasms, especially con-PDAC. \r\n\r\n Methods: The combined databases of pancreatic resections from the Massachusetts General Hospital and the Negrar Hospital, Italy, were analyzed for patients who had been diagnosed with IPMN and concurrent pancreatic or ampullary neoplasms. \r\n\r\n Results: 2762 patients underwent pancreatic surgery from January 2000 to December 2012. Sixteen percent (n = 441) had pathologically confirmed IPMN and 11% of these (n = 50) had a different distinct synchronous pancreatic neoplasm. The majority of these, 62%, were con-PDAC, followed by neuroendocrine neoplasms (10%) and ampullary carcinoma (10%). Less frequently, mucinous (6%) as well as serous cystic neoplasms (6%), adenosquamous carcinoma (4%) and distal bile duct cancer (2%) were diagnosed. Among all patients with synchronous neoplasms, 66% harbored BD-IPMN, 28% combined IPMN and 6% main duct IPMN. Abdominal pain and/or jaundice were the leading symptoms in half of patients. \r\n\r\n Conclusion: IPMN, mainly BD-IPMN, are associated with con-PDAC in about 7% of patients and account for 62% of all concurrent pancreatic/ampullary neoplasms. Other synchronous neoplasms may be found sporadically with IPMN without a suspected association. STN","prediction_labels":"HUMAN"},{"cleaned":"efficacy sequential treatment strategy gemox based followed folfiri based chemotherapy advanced biliary tract cancers background gemcitabine gem platinum chemotherapy stands first line therapy patients recurrent advanced biliary tract cancer btc yielding progression free survival pfs 3 4 6 4 months standard second line chemotherapy gem platinum failure exists data survival benefit remain limited material methods retrospectively reviewed patients recurrent advanced btc received gemcitabine oxaliplatin gemox based chemotherapy followed 5 fluorouracil irinotecan folfiri based chemotherapy evaluate efficacy sequential treatment strategy overall survival os pfs calculated kaplan meier method results fifty two patients analyzed 21 40 intrahepatic 14 27 hilar extrahepatic 17 33 gallbladder cancer median age 64 years range 38 79 years prior curative intent resection primary tumor performed 23 44 2 patients gemox adjuvant chemotherapy given 12 23 1 patients median follow 36 3 months 47 90 4 patients completed treatment strategy first sequence gemox second sequence folfiri achieved 4 8 months 3 2 months median pfs respectively global os sequential chemotherapy 21 9 months sequence folfiri resulted median os 8 4 months conclusion sequence gemox folfiri potential treatment strategy patients recurrent advanced btc pubmed","probabilities":0.9799733,"Title":"Efficacy of a sequential treatment strategy with GEMOX-based followed by FOLFIRI-based chemotherapy in advanced biliary tract cancers","Abstract":"BACKGROUND: Gemcitabine (GEM)-platinum chemotherapy stands as first-line therapy for patients with recurrent/advanced biliary tract cancer (BTC), yielding progression-free survival (PFS) of 3.4-6.4 months. No standard second-line chemotherapy after GEM-platinum failure exists and data on survival benefit remain limited. MATERIAL AND METHODS: We retrospectively reviewed patients with recurrent/advanced BTC who received gemcitabine-oxaliplatin (GEMOX)-based chemotherapy followed by 5-fluorouracil-irinotecan (FOLFIRI)-based chemotherapy to evaluate the efficacy of the sequential treatment strategy. Overall survival (OS) and PFS were calculated by Kaplan-Meier method. RESULTS: Fifty-two patients were analyzed, 21 (40%) had intrahepatic, 14 (27%) had hilar/extrahepatic, and 17 (33%) had gallbladder cancer. Median age was 64 years (range 38-79 years). Prior curative intent resection of the primary tumor was performed in 23 (44.2%) patients and GEMOX adjuvant chemotherapy was given in 12 (23.1%) patients. After a median follow-up of 36.3 months, 47 (90.4%) patients completed the treatment strategy. First-sequence GEMOX and second sequence FOLFIRI achieved 4.8 months and 3.2 months median PFS, respectively. The global OS for the sequential chemotherapy was 21.9 months. The sequence of FOLFIRI resulted in a median OS of 8.4 months. CONCLUSION: The sequence of GEMOX-FOLFIRI is a potential treatment strategy for patients with recurrent/advanced BTC.","Source":"PubMed","category":"HUMAN","training_data":"Efficacy of a sequential treatment strategy with GEMOX-based followed by FOLFIRI-based chemotherapy in advanced biliary tract cancers BACKGROUND: Gemcitabine (GEM)-platinum chemotherapy stands as first-line therapy for patients with recurrent/advanced biliary tract cancer (BTC), yielding progression-free survival (PFS) of 3.4-6.4 months. No standard second-line chemotherapy after GEM-platinum failure exists and data on survival benefit remain limited. MATERIAL AND METHODS: We retrospectively reviewed patients with recurrent/advanced BTC who received gemcitabine-oxaliplatin (GEMOX)-based chemotherapy followed by 5-fluorouracil-irinotecan (FOLFIRI)-based chemotherapy to evaluate the efficacy of the sequential treatment strategy. Overall survival (OS) and PFS were calculated by Kaplan-Meier method. RESULTS: Fifty-two patients were analyzed, 21 (40%) had intrahepatic, 14 (27%) had hilar/extrahepatic, and 17 (33%) had gallbladder cancer. Median age was 64 years (range 38-79 years). Prior curative intent resection of the primary tumor was performed in 23 (44.2%) patients and GEMOX adjuvant chemotherapy was given in 12 (23.1%) patients. After a median follow-up of 36.3 months, 47 (90.4%) patients completed the treatment strategy. First-sequence GEMOX and second sequence FOLFIRI achieved 4.8 months and 3.2 months median PFS, respectively. The global OS for the sequential chemotherapy was 21.9 months. The sequence of FOLFIRI resulted in a median OS of 8.4 months. CONCLUSION: The sequence of GEMOX-FOLFIRI is a potential treatment strategy for patients with recurrent/advanced BTC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidentally discovered gallbladder cancer reoperation cancer gallbladder rare entity poor prognosis often discovered incidentally cholecystectomy tends disseminate early via lymphatic peritoneal endobiliary hematogenous pathways diagnosis made intra operatively quarter cases examination opened cholecystectomy specimen operating room surgeon procedure routine incidentally discovered cancers survival 28 five years prognostic factors include age tnm stage gallbladder perforation cholecystectomy less optimal resection re operation whether laparoscopic route initial cholecystectomy impact survival remains subject debate r0 surgery potentially curative treatment simple cholecystectomy clear margins adequate resection stage t1a tumors extended cholecystectomy lymphadenectomy possibly resection bile duct required advanced stages curative resection neo adjuvant adjuvant chemotherapy radiotherapy far proven effective improvement surgical practices systematic review cholecystectomy specimens prevention gallbladder perforation bile spillage surgery early re intervention optimal resection improve prognosis cancers pubmed","probabilities":0.9799733,"Title":"Incidentally-discovered gallbladder cancer: When, why and which reoperation?","Abstract":"Cancer of the gallbladder, a rare entity with a poor prognosis, is often discovered incidentally during or after cholecystectomy. It tends to disseminate early via lymphatic, peritoneal, endobiliary, and hematogenous pathways. Diagnosis is made intra-operatively in only a quarter of cases, by examination of the opened cholecystectomy specimen in the operating room by the surgeon; this procedure should be routine. For incidentally-discovered cancers, survival was 28% at five years. Prognostic factors include age, TNM stage, gallbladder perforation during cholecystectomy and less-than-optimal resection at re-operation. Whether the laparoscopic route for the initial cholecystectomy has an impact on survival remains a subject of debate. R0 surgery is the only potentially curative treatment: simple cholecystectomy with clear margins is adequate resection for stage T1a tumors; extended cholecystectomy with lymphadenectomy and possibly resection of the bile duct is required for more advanced stages. After curative resection, neo-adjuvant or adjuvant chemotherapy and radiotherapy have not, so far, proven effective. Improvement of surgical practices (systematic review of cholecystectomy specimens in the OR, prevention of gallbladder perforation with bile spillage during surgery, early re-intervention for optimal resection) could improve the prognosis of these cancers.","Source":"PubMed","category":"HUMAN","training_data":"Incidentally-discovered gallbladder cancer: When, why and which reoperation? Cancer of the gallbladder, a rare entity with a poor prognosis, is often discovered incidentally during or after cholecystectomy. It tends to disseminate early via lymphatic, peritoneal, endobiliary, and hematogenous pathways. Diagnosis is made intra-operatively in only a quarter of cases, by examination of the opened cholecystectomy specimen in the operating room by the surgeon; this procedure should be routine. For incidentally-discovered cancers, survival was 28% at five years. Prognostic factors include age, TNM stage, gallbladder perforation during cholecystectomy and less-than-optimal resection at re-operation. Whether the laparoscopic route for the initial cholecystectomy has an impact on survival remains a subject of debate. R0 surgery is the only potentially curative treatment: simple cholecystectomy with clear margins is adequate resection for stage T1a tumors; extended cholecystectomy with lymphadenectomy and possibly resection of the bile duct is required for more advanced stages. After curative resection, neo-adjuvant or adjuvant chemotherapy and radiotherapy have not, so far, proven effective. Improvement of surgical practices (systematic review of cholecystectomy specimens in the OR, prevention of gallbladder perforation with bile spillage during surgery, early re-intervention for optimal resection) could improve the prognosis of these cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"colectomy associated development cholangiocarcinoma patients primary sclerosing cholangitis inflammatory bowel disease abstract available google scholar","probabilities":0.9799733,"Title":"Colectomy Is Associated With Development Of Cholangiocarcinoma In Patients With Primary Sclerosing Cholangitis And Inflammatory Bowel Disease","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Colectomy Is Associated With Development Of Cholangiocarcinoma In Patients With Primary Sclerosing Cholangitis And Inflammatory Bowel Disease Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"conditional survival patients gallbladder cancer background conditional survival cs established clinically relevant prognostic factor cancer sur vivors cs gallbladder gb cancer yet fully evaluated study evaluated cancer specific cs rate cancer specific survival css rate patients gb cancer multiple time points investi gated prognostic factors affect cancer specific cs rate provide accurate survival information methods 2004 2013 total 9760 patients gb cancer identified surveillance epidemiology end results seer data 3 year cancer specific cs rate calculated using covariate adjusted survival function cox model year since diagnosis results analyzed together adjusted css rates time points cox proportional hazards regression performed ascertain individual contribution factors associated css rate diagnosis cancer specific cs rates 1 3 5 years diagnosis results adjusted 5 year css rate 26 1 adjusted 3 year cancer specific cs rates 1 2 3 4 5 years diagnosis 55 5 72 2 81 5 86 8 90 5 respectively time diagnosis age race histology grade n m categories surgery radiotherapy insurance status marriage status significant prognostic fac tors css five years diagnosis however m categories significant prognostic factors survivors p 0 007 p 0 009 respectively whereas surgery radiotherapy conclusions m categories significant prognostic factors even 5 years initial diagnosis whereas local treatments time diagnosis suggesting patients gb cancer high risks might need adjuvant therapy primary treatments combined analysis css cancer specific cs rates offered accurate survival information patients already survived certain period time diagnosis google scholar","probabilities":0.9799733,"Title":"Conditional Survival In Patients With Gallbladder Cancer","Abstract":"Background: Conditional survival (CS) has been established as a clinically relevant prognostic factor for cancer sur‑ vivors, and the CS in gallbladder (GB) cancer has not yet been fully evaluated. In this study, we evaluated the cancer‑ specific CS rate and cancer‑specific survival (CSS) rate in patients with GB cancer at multiple time points and investi‑ gated prognostic factors which affect cancer‑specific CS rate to provide more accurate survival information. Methods: Between 2004 and 2013, a total of 9760 patients with GB cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) data. The 3‑year cancer‑specific CS rate was calculated using the covariate‑ adjusted survival function in the Cox model for each year since diagnosis, and the results were analyzed together with the adjusted CSS rates at the same time points. Cox proportional hazards regression was performed to ascertain the individual contribution of factors associated with CSS rate at diagnosis and cancer‑specific CS rates at 1, 3, and 5 years after diagnosis. Results: The adjusted 5‑year CSS rate was 26.1%. The adjusted 3‑year cancer‑specific CS rates at 1, 2, 3, 4, and 5 years after diagnosis were 55.5, 72.2, 81.5, 86.8, and 90.5%, respectively. At the time of diagnosis, age, race, histology, grade, T, N, and M categories, surgery, radiotherapy, insurance status, and marriage status were significant prognostic fac‑ tors of CSS. Five years after diagnosis, however, T and M categories were significant prognostic factors for survivors (P = 0.007 and P = 0.009, respectively), whereas surgery and radiotherapy were not. Conclusions: T and M categories were significant prognostic factors even 5 years after the initial diagnosis, whereas local treatments at the time of diagnosis were not, suggesting that patients with GB cancer at high risks might need further adjuvant therapy after primary treatments. The combined analysis of CSS and cancer‑specific CS rates offered more accurate survival information for patients who have already survived a certain period of time after diagnosis.","Source":"Google Scholar","category":"HUMAN","training_data":"Conditional Survival In Patients With Gallbladder Cancer Background: Conditional survival (CS) has been established as a clinically relevant prognostic factor for cancer sur‑ vivors, and the CS in gallbladder (GB) cancer has not yet been fully evaluated. In this study, we evaluated the cancer‑ specific CS rate and cancer‑specific survival (CSS) rate in patients with GB cancer at multiple time points and investi‑ gated prognostic factors which affect cancer‑specific CS rate to provide more accurate survival information. Methods: Between 2004 and 2013, a total of 9760 patients with GB cancer were identified from the Surveillance, Epidemiology, and End Results (SEER) data. The 3‑year cancer‑specific CS rate was calculated using the covariate‑ adjusted survival function in the Cox model for each year since diagnosis, and the results were analyzed together with the adjusted CSS rates at the same time points. Cox proportional hazards regression was performed to ascertain the individual contribution of factors associated with CSS rate at diagnosis and cancer‑specific CS rates at 1, 3, and 5 years after diagnosis. Results: The adjusted 5‑year CSS rate was 26.1%. The adjusted 3‑year cancer‑specific CS rates at 1, 2, 3, 4, and 5 years after diagnosis were 55.5, 72.2, 81.5, 86.8, and 90.5%, respectively. At the time of diagnosis, age, race, histology, grade, T, N, and M categories, surgery, radiotherapy, insurance status, and marriage status were significant prognostic fac‑ tors of CSS. Five years after diagnosis, however, T and M categories were significant prognostic factors for survivors (P = 0.007 and P = 0.009, respectively), whereas surgery and radiotherapy were not. Conclusions: T and M categories were significant prognostic factors even 5 years after the initial diagnosis, whereas local treatments at the time of diagnosis were not, suggesting that patients with GB cancer at high risks might need further adjuvant therapy after primary treatments. The combined analysis of CSS and cancer‑specific CS rates offered more accurate survival information for patients who have already survived a certain period of time after diagnosis. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"20 year outcomes study patients immunoglobulin g4 related sclerosing cholangitis mayo clinic experience introduction immunoglobulin g4 related sclerosing cholangitis igg4 sc recognized worldwide however natural history long term outcomes well known methods retrospective single center cohort study identified patients received diagnosis igg4 sc mayo clinic rochester 1999 2018 diagnosis igg4 sc rigorously ascertained review medical records using validated hisort criteria comprehensive clinical data extracted patients charts long term outcomes interest included cirrhosis cholangiocarcinoma cca death compare outcomes random sample psc patients selected 1 1 ratio matched age diagnosis gender survival analyses performed comparisons using kaplan meier method log rank test cumulative incidence cirrhosis cca assessed using competing risks regression method results total 61 patients diagnosed igg4 sc study period median age diagnosis 66 years iqr 56 71 years 85 male median follow 6 1 years iqr 3 2 8 3 years pancreas commonly involved extra biliary organ 93 fifty five patients received prednisone 96 experienced complete partial remission sixteen patients received rituximab maintenance therapy 88 maintained remission three patients 5 developed cirrhosis 2 patients 3 developed cca nine patients 15 died 2 due cirrhosis 2 due cca 1 due pancreatic cancer 4 due non hepatobiliary causes patients igg4 sc significantly lower 5 10 year cumulative incidence developing cirrhosis 5 y 4 vs 34 10 y 6 vs 43 p 0 001 cca 5 y 3 vs 17 10 y 4 vs 22 p 0 012 compared psc patients two patients psc group underwent liver transplantation none igg4 sc group overall 5 10 year survival greater igg4 sc cohort 5 y 92 vs 70 10 y 77 vs 57 p 0 02 conclusion patients igg4 sc majority received treatment small potential risk long term hepatobiliary complications risk cirrhosis cca death lower patients psc better outcome igg4 sc group likely due benefit treatment surveillance population needs assessment especially subset receive respond treatment google scholar","probabilities":0.9799733,"Title":"A 20-Year Outcomes' Study Of Patients With Immunoglobulin G4-Related Sclerosing Cholangitis: The Mayo Clinic Experience","Abstract":"INTRODUCTION:\nImmunoglobulin G4-related sclerosing cholangitis (IgG4-SC) has been recognized worldwide. However, its natural history and long-term outcomes are not well known.\nMETHODS:\nIn this retrospective, single center, cohort study, we identified patients who received a diagnosis of IgG4-SC at Mayo Clinic Rochester from 1999 to 2018. The diagnosis of IgG4-SC was rigorously ascertained by review of medical records and using the validated HISORt criteria. Comprehensive clinical data was extracted from patients' charts. Long-term outcomes of interest included cirrhosis, cholangiocarcinoma (CCA), and death. To compare outcomes, a random sample of PSC patients was selected in a 1:1 ratio matched for age of diagnosis and gender. Survival analyses were performed for comparisons using the Kaplan-Meier method, and log-rank test, and the cumulative incidence of cirrhosis and CCA was assessed using the competing risks regression method.\nRESULTS:\nA total of 61 patients were diagnosed with IgG4-SC during the study period. The median age of diagnosis was 66 years (IQR: 56-71 years), 85% were male, and the median follow-up was 6.1 years (IQR: 3.2-8.3 years). The pancreas was the most commonly involved extra-biliary organ (93%). Fifty-five patients received prednisone of whom 96% experienced complete or partial remission. Sixteen patients received rituximab as maintenance therapy, of whom 88% maintained remission. Three patients (5%) developed cirrhosis, and 2 patients (3%) developed CCA. Nine patients (15%) died; 2 due to cirrhosis, 2 due to CCA, 1 due to pancreatic cancer, and 4 due to non-hepatobiliary causes. Patients with IgG4-SC had significantly lower 5- and 10-year cumulative incidence of developing cirrhosis (5 y: 4% vs. 34%; 10 y: 6% vs. 43%; P < 0.001) and CCA (5 y: 3% vs. 17%; 10 y: 4% vs. 22%; P = 0.012) compared with PSC patients. Two patients in the PSC group underwent liver transplantation, while none in the IgG4-SC group. Overall 5- and 10-year survival was greater in the IgG4-SC cohort (5 y: 92% vs. 70%; 10 y: 77% vs. 57%; P = 0.02).\nCONCLUSION:\nPatients with IgG4-SC, the majority of whom received treatment, have a small potential risk of long-term hepatobiliary complications. Their risk of cirrhosis, CCA and death, was lower than in patients with PSC. The better outcome in the IgG4-SC group is likely due to the benefit of treatment. Surveillance in this population needs further assessment, especially the subset that does receive or respond to treatment.","Source":"Google Scholar","category":"HUMAN","training_data":"A 20-Year Outcomes' Study Of Patients With Immunoglobulin G4-Related Sclerosing Cholangitis: The Mayo Clinic Experience INTRODUCTION:\nImmunoglobulin G4-related sclerosing cholangitis (IgG4-SC) has been recognized worldwide. However, its natural history and long-term outcomes are not well known.\nMETHODS:\nIn this retrospective, single center, cohort study, we identified patients who received a diagnosis of IgG4-SC at Mayo Clinic Rochester from 1999 to 2018. The diagnosis of IgG4-SC was rigorously ascertained by review of medical records and using the validated HISORt criteria. Comprehensive clinical data was extracted from patients' charts. Long-term outcomes of interest included cirrhosis, cholangiocarcinoma (CCA), and death. To compare outcomes, a random sample of PSC patients was selected in a 1:1 ratio matched for age of diagnosis and gender. Survival analyses were performed for comparisons using the Kaplan-Meier method, and log-rank test, and the cumulative incidence of cirrhosis and CCA was assessed using the competing risks regression method.\nRESULTS:\nA total of 61 patients were diagnosed with IgG4-SC during the study period. The median age of diagnosis was 66 years (IQR: 56-71 years), 85% were male, and the median follow-up was 6.1 years (IQR: 3.2-8.3 years). The pancreas was the most commonly involved extra-biliary organ (93%). Fifty-five patients received prednisone of whom 96% experienced complete or partial remission. Sixteen patients received rituximab as maintenance therapy, of whom 88% maintained remission. Three patients (5%) developed cirrhosis, and 2 patients (3%) developed CCA. Nine patients (15%) died; 2 due to cirrhosis, 2 due to CCA, 1 due to pancreatic cancer, and 4 due to non-hepatobiliary causes. Patients with IgG4-SC had significantly lower 5- and 10-year cumulative incidence of developing cirrhosis (5 y: 4% vs. 34%; 10 y: 6% vs. 43%; P < 0.001) and CCA (5 y: 3% vs. 17%; 10 y: 4% vs. 22%; P = 0.012) compared with PSC patients. Two patients in the PSC group underwent liver transplantation, while none in the IgG4-SC group. Overall 5- and 10-year survival was greater in the IgG4-SC cohort (5 y: 92% vs. 70%; 10 y: 77% vs. 57%; P = 0.02).\nCONCLUSION:\nPatients with IgG4-SC, the majority of whom received treatment, have a small potential risk of long-term hepatobiliary complications. Their risk of cirrhosis, CCA and death, was lower than in patients with PSC. The better outcome in the IgG4-SC group is likely due to the benefit of treatment. Surveillance in this population needs further assessment, especially the subset that does receive or respond to treatment. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"k ras mutation amplification status predictive resistance high basal pakt predictive sensitivity everolimus biliary tract cancer cell lines advanced biliary tract cancer btc poor prognosis limited treatment options pi3k akt mtor signalling pathway hyperactivated subset btcs clinical activity mtor inhibitor everolimus observed patients btc goal study identify biomarkers predictive everolimus response twenty btc cell lines assessed everolimus sensitivity spectrum growth inhibitory responses observed molecular biomarkers sensitivity resistance identified interrogation activation status ras mapk pi3k akt mtor pathways k ras mutations amplifications identified 45 cell lines associated resistance everolimus activating mutations pik3ca loss pten predictive everolimus response however high basal levels pakt associated sensitivity independent ras mapk pathway activation status notably everolimus inhibited mtor signalling similar extent sensitive resistant cell lines suggesting relative dependence mtor pathway rather magnitude pathway inhibition determines everolimus response consistent known limitations rapalogs everolimus induced feedback mediated activation akt btc cell lines overcome cotreatment akt inhibitor atp competitive mtorc1 mtorc2 inhibitors however approaches failed induce greater apoptosis compared everolimus mtorc1 mtorc2 kinase inhibitors induced compensatory activation perk identifying inherent limitation agents btc cell lines findings suggest future trials everolimus btc benefit preselecting patients based k ras pi3k mtor pathway activation status study also identifies strategies enhancing inhibition pi3k mtor pathway btc cell lines stn","probabilities":0.9467213,"Title":"K-Ras Mutation And Amplification Status Is Predictive Of Resistance And High Basal Pakt Is Predictive Of Sensitivity To Everolimus In Biliary Tract Cancer Cell Lines","Abstract":"Advanced biliary tract cancer (BTC) has a poor prognosis and limited treatment options. The PI3K/Akt/mTOR signalling pathway is hyperactivated in a subset of BTCs, and clinical activity of the mTOR inhibitor everolimus has been observed in some patients with BTC. The goal of this study was to identify biomarkers predictive of everolimus response. Twenty BTC cell lines were assessed for everolimus sensitivity with a spectrum of growth inhibitory responses observed. Molecular biomarkers of sensitivity and resistance were identified by interrogation of the activation status of the Ras/MAPK and PI3K/Akt/mTOR pathways. K-Ras mutations and/or amplifications were identified in 45% of cell lines and were associated with resistance to everolimus. Activating mutations in PIK3CA or loss of PTEN was not predictive of everolimus response; however, high basal levels of pAKT were associated with sensitivity, independent of Ras/MAPK pathway activation status. Notably, everolimus inhibited mTOR signalling to a similar extent in sensitive and resistant cell lines, suggesting that relative dependence on the mTOR pathway rather than the magnitude of pathway inhibition determines everolimus response. Consistent with the known limitations of rapalogs, everolimus induced feedback-mediated activation of AKT in BTC cell lines, which could be overcome by cotreatment with an AKT inhibitor or ATP-competitive mTORC1/mTORC2 inhibitors. However, both approaches failed to induce greater apoptosis compared to everolimus, and mTORC1/mTORC2 kinase inhibitors induced compensatory activation of pERK, identifying an inherent limitation of these agents in BTC cell lines. These findings suggest that future trials of everolimus in BTC would benefit from preselecting patients based on their K-Ras and PI3K/mTOR pathway activation status. The study also identifies strategies for enhancing inhibition of the PI3K/mTOR pathway in BTC cell lines.","Source":"STN","category":"ANIMAL","training_data":"K-Ras Mutation And Amplification Status Is Predictive Of Resistance And High Basal Pakt Is Predictive Of Sensitivity To Everolimus In Biliary Tract Cancer Cell Lines Advanced biliary tract cancer (BTC) has a poor prognosis and limited treatment options. The PI3K/Akt/mTOR signalling pathway is hyperactivated in a subset of BTCs, and clinical activity of the mTOR inhibitor everolimus has been observed in some patients with BTC. The goal of this study was to identify biomarkers predictive of everolimus response. Twenty BTC cell lines were assessed for everolimus sensitivity with a spectrum of growth inhibitory responses observed. Molecular biomarkers of sensitivity and resistance were identified by interrogation of the activation status of the Ras/MAPK and PI3K/Akt/mTOR pathways. K-Ras mutations and/or amplifications were identified in 45% of cell lines and were associated with resistance to everolimus. Activating mutations in PIK3CA or loss of PTEN was not predictive of everolimus response; however, high basal levels of pAKT were associated with sensitivity, independent of Ras/MAPK pathway activation status. Notably, everolimus inhibited mTOR signalling to a similar extent in sensitive and resistant cell lines, suggesting that relative dependence on the mTOR pathway rather than the magnitude of pathway inhibition determines everolimus response. Consistent with the known limitations of rapalogs, everolimus induced feedback-mediated activation of AKT in BTC cell lines, which could be overcome by cotreatment with an AKT inhibitor or ATP-competitive mTORC1/mTORC2 inhibitors. However, both approaches failed to induce greater apoptosis compared to everolimus, and mTORC1/mTORC2 kinase inhibitors induced compensatory activation of pERK, identifying an inherent limitation of these agents in BTC cell lines. These findings suggest that future trials of everolimus in BTC would benefit from preselecting patients based on their K-Ras and PI3K/mTOR pathway activation status. The study also identifies strategies for enhancing inhibition of the PI3K/mTOR pathway in BTC cell lines. STN","prediction_labels":"ANIMAL"},{"cleaned":"hepato pancreatoduodenectomy wide spread bile duct cancer introduction hepato pancreatoduodenectomy hpd definitive surgery r0 resection wide spread bile duct cancer even today remains controversial report treatment results hpd wide spread bile duct cancer department method 1992 2017 217 patients underwent hepatectomy extrahepatic bile duct resection due bile duct cancer department 23 cases underwent hpd hpd group 194 cases underwent hepatectomy hx group examined surgical factors short term result long term result two groups result operation time significantly prolonged hpd group hpd 1010 143 min vs hx 789 160 min p 0 001 although difference blood loss two groups rate transfusion high cases hpd p 0 047 morbidity rate high hpd group hpd 16 cases 69 6 vs hx 98 cases 50 8 p 0 088 pancreatic fistula grade b higher detected 4 23 cases hpd group one patients pancreatic fistula introduction pancreatico gastrostomy mortality observed 3 cases 13 0 hpd group 11 cases 5 7 hx group p 0 174 five years survival rates 41 5 hpd group 37 9 hx group p 0 305 five years survival rates patents positive ductal margin duodenal side 11 4 conclusion hpd wide spread bile duct cancer might acceptable surgical invasiveness morbidity mortality rates pancreatico gastrostomy performed countermeasure pancreatic fistula thought contribute improved safety google scholar","probabilities":0.9799733,"Title":"Hepato-Pancreatoduodenectomy For Wide-Spread Bile Duct Cancer","Abstract":"Introduction: Hepato-pancreatoduodenectomy (HPD) is a definitive surgery for R0 resection of wide - spread bile duct cancer, but even today it remains controversial. We report the treatment results of HPD for wide-spread bile duct cancer in our department.\nMethod: From 1992 to 2017, 217 patients underwent hepatectomy with extrahepatic bile duct resection due to bile duct cancer in our department, 23 cases who underwent HPD (HPD group) and 194 cases who underwent hepatectomy (Hx group). We examined the surgical factors, short term result and long- term result with two groups.\nResult: The operation time was significantly prolonged in HPD group (HPD: 1010 ± 143 min vs Hx: 789 ± 160 min, p <0.001). Although there was no difference in blood loss between the two groups, the rate of transfusion was high in the cases of HPD (P = 0.047). The morbidity rate was high in HPD group (HPD: 16 cases (69.6%) vs Hx: 98 cases (50.8%) , p=0.088). Pancreatic fistula (Grade B or higher) was detected in 4 of 23 cases in the HPD group, but there was only one patients with pancreatic fistula after introduction of pancreatico-gastrostomy. Mortality was observed in 3 cases (13.0%) in HPD group and 11 cases (5.7%) in Hx group (p=0.174). The five years survival rates was 41.5% in HPD group and 37.9% in Hx group (p=0.305). The five years survival rates of patents with positive ductal margin at the duodenal side was 11.4%.\nConclusion: HPD for wide-spread bile duct cancer might be acceptable for surgical invasiveness, morbidity and mortality rates. Pancreatico - gastrostomy performed as a countermeasure against pancreatic fistula was thought to contribute to the improved safety.","Source":"Google Scholar","category":"HUMAN","training_data":"Hepato-Pancreatoduodenectomy For Wide-Spread Bile Duct Cancer Introduction: Hepato-pancreatoduodenectomy (HPD) is a definitive surgery for R0 resection of wide - spread bile duct cancer, but even today it remains controversial. We report the treatment results of HPD for wide-spread bile duct cancer in our department.\nMethod: From 1992 to 2017, 217 patients underwent hepatectomy with extrahepatic bile duct resection due to bile duct cancer in our department, 23 cases who underwent HPD (HPD group) and 194 cases who underwent hepatectomy (Hx group). We examined the surgical factors, short term result and long- term result with two groups.\nResult: The operation time was significantly prolonged in HPD group (HPD: 1010 ± 143 min vs Hx: 789 ± 160 min, p <0.001). Although there was no difference in blood loss between the two groups, the rate of transfusion was high in the cases of HPD (P = 0.047). The morbidity rate was high in HPD group (HPD: 16 cases (69.6%) vs Hx: 98 cases (50.8%) , p=0.088). Pancreatic fistula (Grade B or higher) was detected in 4 of 23 cases in the HPD group, but there was only one patients with pancreatic fistula after introduction of pancreatico-gastrostomy. Mortality was observed in 3 cases (13.0%) in HPD group and 11 cases (5.7%) in Hx group (p=0.174). The five years survival rates was 41.5% in HPD group and 37.9% in Hx group (p=0.305). The five years survival rates of patents with positive ductal margin at the duodenal side was 11.4%.\nConclusion: HPD for wide-spread bile duct cancer might be acceptable for surgical invasiveness, morbidity and mortality rates. Pancreatico - gastrostomy performed as a countermeasure against pancreatic fistula was thought to contribute to the improved safety. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"comparative survival safety analysis cisplatin based regimens gall bladder cancer patients retrospective cohort study aim retrospective cohort study patients treated different regimens adjuvant chemotherapy cholecystectomy due gall bladder cancer gbc patients methods data gbc patients registered january 2011 january 2015 mahavir cancer sansthan treated 5 fu plus cisplatin gemcitabine plus cisplatin adjuvant chemotherapy reviewed retrospectively eighty patients enrolled data analysed overall survival progression free survival causality preventability severity adverse drug reactions adrs also evaluated results forty patients assigned 5fu cis gem cis 5fu cis gave adrs gem cis incidence adrs 5fu cis regimen 62 5 gem cis 40 according modified hartwig siegel scale 80 adrs shown 5fu cis moderately severe based modified schumock thornton preventability scale 5fu cis gem cis showed 90 80 preventable adrs respectively per umc causality assessment scale 80 certain 5fu cis gem cis showed mean os 11 2 months 95 ci 10 6 11 8 mean pfs 7 4 months 95 ci 7 3 8 4 5fu cis mean os 8 1 months 95 ci 7 7 8 4 mean pfs 3 4 months 95 ci 3 8 4 1 conclusion direct comparison 5fu cis gem cis showed latter regimen superior os pfs prospective studies define efficacy toxicity regimens recommended google scholar","probabilities":0.9799733,"Title":"Comparative Survival And Safety Analysis Of Cisplatin Based Regimens In Gall Bladder Cancer Patients: A Retrospective Cohort Study","Abstract":"Aim: This is a retrospective cohort study of patients who were treated with different regimens of adjuvant chemotherapy after cholecystectomy due to Gall Bladder Cancer (GBC).\nPatients and Methods: Data of GBC Patients registered between January 2011 to January 2015 at Mahavir Cancer Sansthan treated with 5-FU plus Cisplatin and Gemcitabine plus Cisplatin as adjuvant chemotherapy were reviewed retrospectively. Eighty patients were enrolled and data was analysed for overall survival and progression free survival. Causality, preventability and severity of Adverse Drug Reactions (ADRs) were also evaluated.\nResults: Forty patients were assigned with 5FU-Cis and Gem-Cis each. 5FU-Cis gave more ADRs than Gem-Cis. Incidence of ADRs in 5FU-Cis regimen was 62.5% and that of Gem-Cis was 40%. According Modified Hartwig and Siegel scale, “80%” of ADRs shown by 5FU-Cis were moderately severe. Based on Modified Schumock & Thornton Preventability scale, 5FU-Cis and Gem-Cis showed “90%” and “80%” Not Preventable ADRs respectively. As per WHO-UMC Causality assessment scale, “80%” were certain with 5FU-Cis. Gem-Cis showed a mean OS of 11.2 months (95% CI, 10.6-11.8) and mean PFS of 7.4 months (95% CI, 7.3-8.4). 5FU-Cis had a mean OS of 8.1 months (95% CI, 7.7-8.4) and mean PFS of 3.4 months (95% CI, 3.8-4.1).\nConclusion: Direct comparison of 5FU-Cis and Gem-Cis showed the latter regimen was superior in OS and PFS. Further prospective studies which define the efficacy and toxicity of these regimens are recommended.","Source":"Google Scholar","category":"HUMAN","training_data":"Comparative Survival And Safety Analysis Of Cisplatin Based Regimens In Gall Bladder Cancer Patients: A Retrospective Cohort Study Aim: This is a retrospective cohort study of patients who were treated with different regimens of adjuvant chemotherapy after cholecystectomy due to Gall Bladder Cancer (GBC).\nPatients and Methods: Data of GBC Patients registered between January 2011 to January 2015 at Mahavir Cancer Sansthan treated with 5-FU plus Cisplatin and Gemcitabine plus Cisplatin as adjuvant chemotherapy were reviewed retrospectively. Eighty patients were enrolled and data was analysed for overall survival and progression free survival. Causality, preventability and severity of Adverse Drug Reactions (ADRs) were also evaluated.\nResults: Forty patients were assigned with 5FU-Cis and Gem-Cis each. 5FU-Cis gave more ADRs than Gem-Cis. Incidence of ADRs in 5FU-Cis regimen was 62.5% and that of Gem-Cis was 40%. According Modified Hartwig and Siegel scale, “80%” of ADRs shown by 5FU-Cis were moderately severe. Based on Modified Schumock & Thornton Preventability scale, 5FU-Cis and Gem-Cis showed “90%” and “80%” Not Preventable ADRs respectively. As per WHO-UMC Causality assessment scale, “80%” were certain with 5FU-Cis. Gem-Cis showed a mean OS of 11.2 months (95% CI, 10.6-11.8) and mean PFS of 7.4 months (95% CI, 7.3-8.4). 5FU-Cis had a mean OS of 8.1 months (95% CI, 7.7-8.4) and mean PFS of 3.4 months (95% CI, 3.8-4.1).\nConclusion: Direct comparison of 5FU-Cis and Gem-Cis showed the latter regimen was superior in OS and PFS. Further prospective studies which define the efficacy and toxicity of these regimens are recommended. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact cd8 cell distribution association hla class expression intrahepatic cholangiocarcinoma purpose lack effective systemic therapy one reason poor prognosis intrahepatic cholangiocarcinoma newly developed immune checkpoint inhibitors function minimizing cd8 cell suppression improve tumor specific responses study aimed examine characteristics cd8 cells intrahepatic cholangiocarcinoma methods clinicopathological data including overall survival 69 cases postoperative intrahepatic cholangiocarcinoma prospectively investigated immunohistochemically stained cd8 foxp3 cd163 pd l1 human leukocyte antigen hla class counted number cd8 cells foxp3 cells cd163 macrophages different areas outer border interborder intratumor results significant difference found 5 year overall survival cd8 cell high group 45 5 low group 24 7 outer border area p 0 0103 furthermore number cd8 cells high expression hla class positively correlated p 0 0341 conclusion number cd8 cells outer border area tumor correlated hla class expression intrahepatic cholangiocarcinoma may therefore prognostic factor patients postoperative intrahepatic cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Prognostic Impact Of Cd8+ T Cell Distribution And Its Association With The Hla Class I Expression In Intrahepatic Cholangiocarcinoma","Abstract":"Purpose: A lack of effective systemic therapy is one reason for the poor prognosis of intrahepatic cholangiocarcinoma. Newly developed immune checkpoint inhibitors function by minimizing CD8+ T cell suppression to improve tumor-specific responses. This study aimed to examine the characteristics of CD8+ T cells in intrahepatic cholangiocarcinoma. \r\n\r\n Methods: Clinicopathological data, including the overall survival, of 69 cases of postoperative intrahepatic cholangiocarcinoma were prospectively investigated. We then immunohistochemically stained for CD8, Foxp3, CD163, PD-L1, and human leukocyte antigen (HLA) class I and counted the number of CD8+ T cells, Foxp3+ T cells, and CD163+ macrophages in different areas (outer border, interborder, and intratumor). \r\n\r\n Results: A significant difference was found in the 5-year overall survival between the CD8+ T cell high group (45.5%) and low group (24.7%) in the outer border area (p = 0.0103). Furthermore, the number of CD8+ T cells and the high expression of HLA class I were positively correlated (p = 0.0341). \r\n\r\n Conclusion: The number of CD8+ T cells in the outer border area of the tumor correlated with the HLA class I expression of intrahepatic cholangiocarcinoma and may therefore be a prognostic factor for patients with postoperative intrahepatic cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Prognostic Impact Of Cd8+ T Cell Distribution And Its Association With The Hla Class I Expression In Intrahepatic Cholangiocarcinoma Purpose: A lack of effective systemic therapy is one reason for the poor prognosis of intrahepatic cholangiocarcinoma. Newly developed immune checkpoint inhibitors function by minimizing CD8+ T cell suppression to improve tumor-specific responses. This study aimed to examine the characteristics of CD8+ T cells in intrahepatic cholangiocarcinoma. \r\n\r\n Methods: Clinicopathological data, including the overall survival, of 69 cases of postoperative intrahepatic cholangiocarcinoma were prospectively investigated. We then immunohistochemically stained for CD8, Foxp3, CD163, PD-L1, and human leukocyte antigen (HLA) class I and counted the number of CD8+ T cells, Foxp3+ T cells, and CD163+ macrophages in different areas (outer border, interborder, and intratumor). \r\n\r\n Results: A significant difference was found in the 5-year overall survival between the CD8+ T cell high group (45.5%) and low group (24.7%) in the outer border area (p = 0.0103). Furthermore, the number of CD8+ T cells and the high expression of HLA class I were positively correlated (p = 0.0341). \r\n\r\n Conclusion: The number of CD8+ T cells in the outer border area of the tumor correlated with the HLA class I expression of intrahepatic cholangiocarcinoma and may therefore be a prognostic factor for patients with postoperative intrahepatic cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"as2o3 increases sensitivity cholangiocarcinoma 5 fluorouracil microrna 885 5p mtpn axis objective investigate effects il 2 il 15 stem cell factor scf efficiency expansion expression nkg2d cytotoxcity cd3 cd56 cd16 nk cells human hepatocellular carcinoma cell lines methods cd3 cd56 cd16 nk cells purified sorting method macs magnetic microbeads activated cells sorting expanded presence il 2 il 15 il 2 il 15 scf without anti nkg2d monoclonal antibody efficiency expansion expression nkg2d google scholar","probabilities":0.9467213,"Title":"As2O3 Increases Sensitivity Of Cholangiocarcinoma To 5-Fluorouracil Through The Microrna-885-5P/Mtpn Axis","Abstract":"Objective To investigate the effects of IL-2, IL-15 and stem cell factor (SCF) on the efficiency \nof expansion, expression of NKG2D and the cytotoxcity of CD3-CD56+CD16+ NK cells \nagainst human hepatocellular carcinoma cell lines. Methods The CD3-CD56+CD16+ NK \ncells purified by the sorting method of MACS (magnetic microbeads activated cells sorting) \nwere expanded in the presence of IL-2 or IL-15 or IL-2/IL-15/SCF with or without anti-NKG2D \nmonoclonal antibody. The efficiency of expansion, the expression of NKG2D and the …","Source":"Google Scholar","category":"ANIMAL","training_data":"As2O3 Increases Sensitivity Of Cholangiocarcinoma To 5-Fluorouracil Through The Microrna-885-5P/Mtpn Axis Objective To investigate the effects of IL-2, IL-15 and stem cell factor (SCF) on the efficiency \nof expansion, expression of NKG2D and the cytotoxcity of CD3-CD56+CD16+ NK cells \nagainst human hepatocellular carcinoma cell lines. Methods The CD3-CD56+CD16+ NK \ncells purified by the sorting method of MACS (magnetic microbeads activated cells sorting) \nwere expanded in the presence of IL-2 or IL-15 or IL-2/IL-15/SCF with or without anti-NKG2D \nmonoclonal antibody. The efficiency of expansion, the expression of NKG2D and the … Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"preoperative platelet lymphocyte ratio neutrophil lymphocyte ratio predictors clinical outcome patients gallbladder cancer inflammatory biomarkers associated post surgical prognosis cancer patients however clinical importance gallbladder cancer rarely explored aim study assess efficacy surgical intervention effectiveness preoperative test neutrophil lymphocyte ratio nlr platelet lymphocyte ratio plr monocyte lymphocyte ratio mlr predicting prognosis gallbladder cancer patients study total 255 gallbladder cancer patients retrospectively selected patient recorded treatment algorithm without surgery preoperative inflammatory biomarkers well detailed survival information 5 years total 216 patients received surgical intervention 39 chose conservative treatment median survival time 4 6 months non surgical group p 0 001 12 2 months surgical intervention group among surgical group roc analysis showed auc nlr plr mlr 0 675 95 ci 0 600 0 751 p 0 001 0 599 95 ci 0 520 0 677 p 0 017 0 607 95 ci 0 529 0 686 p 0 009 respectively conclusion surgical intervention improve overall survival elevated nlr mlr surgery associated shorter os gbc patients google scholar","probabilities":0.9799733,"Title":"Preoperative Platelet-To-Lymphocyte Ratio And Neutrophil-To-Lymphocyte Ratio As Predictors Of Clinical Outcome In Patients With Gallbladder Cancer","Abstract":"Some inflammatory biomarkers are associated with the post-surgical prognosis in cancer patients. However, their clinical importance in gallbladder cancer has rarely been explored. The aim of this study is to assess the efficacy of surgical intervention and the effectiveness of preoperative test on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) for predicting the prognosis in gallbladder cancer patients. In this study, a total of 255 gallbladder cancer patients were retrospectively selected. For each patient, we recorded his/her treatment algorithm (with or without surgery) and their preoperative inflammatory biomarkers, as well as their detailed survival information for 5 years. A total of 216 patients received surgical intervention and the other 39 chose conservative treatment. The median survival time was 4.6 months for non-surgical group (P < 0.001), and 12.2 months for surgical intervention group. Among the surgical group, ROC analysis showed the AUC of NLR, PLR and MLR were 0.675 (95% CI: 0.600 to 0.751, P < 0.001), 0.599 (95% CI: 0.520 to 0.677, P = 0.017) and 0.607 (95% CI: 0.529 to 0.686, P = 0.009), respectively. In conclusion, surgical intervention did improve the overall survival, and elevated NLR and MLR before surgery are associated with shorter OS of GBC patients.","Source":"Google Scholar","category":"HUMAN","training_data":"Preoperative Platelet-To-Lymphocyte Ratio And Neutrophil-To-Lymphocyte Ratio As Predictors Of Clinical Outcome In Patients With Gallbladder Cancer Some inflammatory biomarkers are associated with the post-surgical prognosis in cancer patients. However, their clinical importance in gallbladder cancer has rarely been explored. The aim of this study is to assess the efficacy of surgical intervention and the effectiveness of preoperative test on neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR) for predicting the prognosis in gallbladder cancer patients. In this study, a total of 255 gallbladder cancer patients were retrospectively selected. For each patient, we recorded his/her treatment algorithm (with or without surgery) and their preoperative inflammatory biomarkers, as well as their detailed survival information for 5 years. A total of 216 patients received surgical intervention and the other 39 chose conservative treatment. The median survival time was 4.6 months for non-surgical group (P < 0.001), and 12.2 months for surgical intervention group. Among the surgical group, ROC analysis showed the AUC of NLR, PLR and MLR were 0.675 (95% CI: 0.600 to 0.751, P < 0.001), 0.599 (95% CI: 0.520 to 0.677, P = 0.017) and 0.607 (95% CI: 0.529 to 0.686, P = 0.009), respectively. In conclusion, surgical intervention did improve the overall survival, and elevated NLR and MLR before surgery are associated with shorter OS of GBC patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"concurrent analysis human equilibrative nucleoside transporter 1 ribonucleotide reductase subunit 1 expression increases predictive value prognosis cholangiocarcinoma patients treated adjuvant gemcitabine based chemotherapy background aim study investigate predictive prognostic values intratumoural human equilibrative nucleoside transporter 1 hent1 ribonucleotide reductase subunit 1 rrm1 expression advanced cholangiocarcinoma patients treated adjuvant gemcitabine based chemotherapy agc methods intratumoural hent1 rrm1 expression levels investigated immunohistochemically 127 patients advanced cholangiocarcinoma underwent surgical resection 68 agc 59 without agc impacts hent1 rrm1 expression survival evaluated results high intratumoural hent1 rrm1 expression levels observed 86 68 67 53 patients respectively multivariate analysis 68 patients received agc high hent1 p 0 044 low rrm1 expression p 0 009 independently associated prolonged disease free survival dfs whereas low rrm1 expression p 0 024 independently associated prolonged overall survival os moreover concurrent high hent1 low rrm1 expression powerful independent predictor prolonged dfs p 0 001 os p 0 001 combined classification hent1 rrm1 introduced conclusions concurrent analysis hent1 rrm1 expression may increase predictive value biomarkers survival advanced cholangiocarcinoma patients treated agc pubmed","probabilities":0.8684211,"Title":"Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy","Abstract":"BACKGROUND: The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC). METHODS: Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated. RESULTS: High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced. CONCLUSIONS: Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC.","Source":"PubMed","category":"HUMAN","training_data":"Concurrent analysis of human equilibrative nucleoside transporter 1 and ribonucleotide reductase subunit 1 expression increases predictive value for prognosis in cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy BACKGROUND: The aim of this study was to investigate the predictive and prognostic values of intratumoural human equilibrative nucleoside transporter 1 (hENT1) and ribonucleotide reductase subunit 1 (RRM1) expression in advanced cholangiocarcinoma patients treated with adjuvant gemcitabine-based chemotherapy (AGC). METHODS: Intratumoural hENT1 and RRM1 expression levels were investigated immunohistochemically in 127 patients with advanced cholangiocarcinoma who underwent surgical resection (68 with AGC and 59 without AGC). The impacts of hENT1 and RRM1 expression on survival were evaluated. RESULTS: High intratumoural hENT1 and RRM1 expression levels were observed in 86 (68%) and 67 (53%) patients, respectively. In a multivariate analysis of 68 patients who received AGC, high hENT1 (P=0.044) and low RRM1 expression (P=0.009) were independently associated with prolonged disease-free survival (DFS), whereas low RRM1 expression (P=0.024) was independently associated with prolonged overall survival (OS). Moreover, concurrent high hENT1 and low RRM1 expression was a powerful independent predictor of prolonged DFS (P<0.001) and OS (P=0.001) when the combined classification of hENT1 and RRM1 was introduced. CONCLUSIONS: Concurrent analysis of hENT1 and RRM1 expression may increase the predictive value of these biomarkers for survival of advanced cholangiocarcinoma patients treated with AGC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"risk colorectal neoplasia patients gallbladder diseases cholecystectomy associated increased risk colorectal cancer little known relationship gallbladder disease colorectal adenoma gallbladder polyps colorectal neoplasia crn share several risk factors obesity diabetes metabolic syndrome might account association study investigated whether asymptomatic patients gallbladder disease increased risk crn identified factors association study population consisted 4 626 consecutive asymptomatic individuals drawn prospective health check cohort underwent ultrasonography colonoscopy screening prevalence crns patients gallbladder polyps gallstones significantly higher control group 32 1 vs 26 8 p 0 032 35 8 vs 26 9 p 0 020 multivariate regression analysis showed gallbladder polyps independent risk factor crn adjusted odds ratio 1 29 95 confidence interval ci 1 03 1 62 whereas gallstones adjusted 1 14 95 ci 0 79 1 63 adjusted risk crn 1 12 gallbladder polyps 5 mm 95 ci 0 85 1 46 1 79 gallbladder polyps 5 mm 95 ci 1 15 2 77 prevalence crn increased increasing polyp size p trend 0 022 results suggest colorectal neoplasia significantly related gallbladder polyps especially 5 mm pubmed","probabilities":0.9799733,"Title":"The Risk of Colorectal Neoplasia in Patients with Gallbladder Diseases","Abstract":"Cholecystectomy is associated with an increased risk of colorectal cancer, but little is known about the relationship between gallbladder disease and colorectal adenoma. Gallbladder polyps and colorectal neoplasia (CRN) share several risk factors such as obesity, diabetes and metabolic syndrome, which might account for their association. In this study, we investigated whether asymptomatic patients with gallbladder disease are at increased risk of CRN and identified the factors to their association. The study population consisted of 4,626 consecutive, asymptomatic individuals drawn from a prospective health check-up cohort who underwent both ultrasonography and colonoscopy screening. The prevalence of CRNs in patients with gallbladder polyps or gallstones was significantly higher than that in the control group (32.1% vs. 26.8%; P = 0.032, 35.8% vs. 26.9%; P = 0.020). A multivariate regression analysis showed that gallbladder polyps were an independent risk factor for CRN [adjusted odds ratio (OR): 1.29; 95% confidence interval (CI); 1.03-1.62] whereas gallstones were not (adjusted OR: 1.14; 95% CI: 0.79-1.63). The adjusted OR for the risk of CRN was 1.12 for gallbladder polyps < 5 mm (95% CI, 0.85-1.46) and 1.79 for gallbladder polyps ≥ 5 mm (95% CI, 1.15-2.77). The prevalence of CRN increased with increasing polyp size (P trend = 0.022). Our results suggest that colorectal neoplasia is significantly related to gallbladder polyps, especially those ≥ 5 mm.","Source":"PubMed","category":"HUMAN","training_data":"The Risk of Colorectal Neoplasia in Patients with Gallbladder Diseases Cholecystectomy is associated with an increased risk of colorectal cancer, but little is known about the relationship between gallbladder disease and colorectal adenoma. Gallbladder polyps and colorectal neoplasia (CRN) share several risk factors such as obesity, diabetes and metabolic syndrome, which might account for their association. In this study, we investigated whether asymptomatic patients with gallbladder disease are at increased risk of CRN and identified the factors to their association. The study population consisted of 4,626 consecutive, asymptomatic individuals drawn from a prospective health check-up cohort who underwent both ultrasonography and colonoscopy screening. The prevalence of CRNs in patients with gallbladder polyps or gallstones was significantly higher than that in the control group (32.1% vs. 26.8%; P = 0.032, 35.8% vs. 26.9%; P = 0.020). A multivariate regression analysis showed that gallbladder polyps were an independent risk factor for CRN [adjusted odds ratio (OR): 1.29; 95% confidence interval (CI); 1.03-1.62] whereas gallstones were not (adjusted OR: 1.14; 95% CI: 0.79-1.63). The adjusted OR for the risk of CRN was 1.12 for gallbladder polyps < 5 mm (95% CI, 0.85-1.46) and 1.79 for gallbladder polyps ≥ 5 mm (95% CI, 1.15-2.77). The prevalence of CRN increased with increasing polyp size (P trend = 0.022). Our results suggest that colorectal neoplasia is significantly related to gallbladder polyps, especially those ≥ 5 mm. PubMed","prediction_labels":"HUMAN"},{"cleaned":"nomogram predict overall survival biliary tract cancer background aim study develop validate nomogram predict overall survival os biliary tract cancer btc patients methods patients diagnosed btc 2004 2014 selected study surveillance epidemiology end results seer database patients randomly allocated 2 sets training set n 8 869 validation set n 8 766 purposes validation prognostic effects variable examined using univariate multivariate analyses cox regression models nomogram developed based significant prognostic factors predictive discriminatory capacity nomogram evaluated harrell concordance index c index calibration plots results data 17 635 patients btc collected seer database age race tumor site tumor grade n m stage marital status therapy associated survival multivariate models factors integrated construct nomogram nomogram predicting os displayed better discrimination power tumor node metastasis tnm stage system 6th edition training set validation set calibration curve indicated nomogram able accurately predict 3 5 year os conclusion predictive model potential provide individualized risk estimate survival patients btc google scholar","probabilities":0.9799733,"Title":"A Nomogram To Predict Overall Survival For Biliary Tract Cancer","Abstract":"Background\nThe aim of the study was to develop and validate a nomogram to predict overall survival (OS) in biliary tract cancer (BTC).\nPatients and methods\nPatients diagnosed with BTC between 2004 and 2014 were selected for the study from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly allocated to 2 sets, the training set (n = 8,869) and the validation set (n = 8,766), for the purposes of validation. The prognostic effects of each variable were examined using univariate and multivariate analyses. Cox regression models and a nomogram were developed based on significant prognostic factors. The predictive and discriminatory capacity of the nomogram was evaluated by Harrell’s concordance index (C-index) and calibration plots.\nResults\nData of 17,635 patients with BTC were collected from the SEER database. Age; race; tumor site; tumor grade; T, N, and M stage; marital status; and therapy were associated with survival in the multivariate models. All these factors were integrated to construct the nomogram. The nomogram for predicting OS displayed better discrimination power than the tumor-node-metastasis (TNM) stage system 6th edition in the training set and validation set. The calibration curve indicated that the nomogram was able to accurately predict 3- and 5-year OS.\nConclusion\nThis predictive model has the potential to provide an individualized risk estimate of survival in patients with BTC.","Source":"Google Scholar","category":"HUMAN","training_data":"A Nomogram To Predict Overall Survival For Biliary Tract Cancer Background\nThe aim of the study was to develop and validate a nomogram to predict overall survival (OS) in biliary tract cancer (BTC).\nPatients and methods\nPatients diagnosed with BTC between 2004 and 2014 were selected for the study from the Surveillance, Epidemiology, and End Results (SEER) database. All patients were randomly allocated to 2 sets, the training set (n = 8,869) and the validation set (n = 8,766), for the purposes of validation. The prognostic effects of each variable were examined using univariate and multivariate analyses. Cox regression models and a nomogram were developed based on significant prognostic factors. The predictive and discriminatory capacity of the nomogram was evaluated by Harrell’s concordance index (C-index) and calibration plots.\nResults\nData of 17,635 patients with BTC were collected from the SEER database. Age; race; tumor site; tumor grade; T, N, and M stage; marital status; and therapy were associated with survival in the multivariate models. All these factors were integrated to construct the nomogram. The nomogram for predicting OS displayed better discrimination power than the tumor-node-metastasis (TNM) stage system 6th edition in the training set and validation set. The calibration curve indicated that the nomogram was able to accurately predict 3- and 5-year OS.\nConclusion\nThis predictive model has the potential to provide an individualized risk estimate of survival in patients with BTC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"predictive factors severe complications ampullary bile duct duodenal cancers following pancreaticoduodenectomy multivariate analysis 10 year multicentre retrospective series background postoperative outcomes following pancreaticoduodenectomy well described pancreatic cancers due lower incidence rate complication rates relative predictive factors less detailed ampullary bile duct duodenal cancers methods medical charts patients operated 2001 2011 ampullary bile duct duodenal cancer reviewed data retrospectively studied respect demographics surgical management postoperative complications histological findings specific complication rates reported predictive factors severe morbidity mortality determined multivariate analysis results 135 patients identified 55 ampullary 55 bile duct 25 duodenal cancers twelve patients 8 9 deceased postoperatively 36 others 26 7 presented severe complications sixty seven percent pancreas soft pancreatic hardness found main protective factor severe morbidity hr 0 36 95 ci 0 14 0 94 p 0 037 age postpancreatectomy haemorrhage independent predictors death hr 14 63 95 ci 1 57 135 77 p 0 018 hr 14 71 95 ci 2 86 75 62 p 0 001 respectively use external transanastomotic duct stent significantly reduced morbidity hr 0 37 95 ci 0 16 0 83 p 0 016 mortality hr 0 12 95 ci 0 02 0 69 p 0 017 conclusions pancreaticoduodenectomy ampullary bile duct duodenal cancers high risk procedure systematic use transanastomotic duct stents significantly decrease complication rate older patients beneficiate specific preoperative evaluation using adapted index omental flap techniques prevent postpancreatectomy haemorrhage efficient effects preoperative octreotid harden pancreas clarified pubmed","probabilities":0.9799733,"Title":"Predictive factors of severe complications for ampullary, bile duct and duodenal cancers following pancreaticoduodenectomy: Multivariate analysis of a 10-year multicentre retrospective series","Abstract":"BACKGROUND: Postoperative outcomes following pancreaticoduodenectomy are well described for pancreatic cancers. Due to a lower incidence rate, complication rates and relative predictive factors are less detailed for ampullary, bile duct and duodenal cancers. METHODS: Medical charts of patients operated on between 2001 and 2011 for an ampullary, bile duct or duodenal cancer were reviewed. Data were retrospectively studied with respect to demographics, surgical management, postoperative complications and histological findings. Specific complication rates were reported, and predictive factors for severe morbidity and mortality were determined by multivariate analysis. RESULTS: 135 patients were identified: 55 ampullary, 55 bile duct and 25 duodenal cancers. Twelve patients (8.9%) deceased postoperatively, and 36 others (26.7%) presented severe complications. Sixty-seven percent of the pancreas was soft, and pancreatic hardness was found to be the main protective factor against severe morbidity (HR = 0.36, 95% CI = 0.14-0.94, P = 0.037). Age and postpancreatectomy haemorrhage were independent predictors for death (HR = 14.63, 95% CI = 1.57-135.77, P = 0.018, and HR = 14.71, 95% CI = 2.86-75.62, P = 0.001, respectively). Only the use of an external transanastomotic duct stent significantly reduced both the morbidity (HR = 0.37, 95% CI = 0.16-0.83, P = 0.016), and the mortality (HR = 0.12, 95% CI = 0.02-0.69, P = 0.017). CONCLUSIONS: Pancreaticoduodenectomy for ampullary, bile duct and duodenal cancers is a high-risk procedure. The systematic use of transanastomotic duct stents would significantly decrease the complication rate. Older patients should beneficiate from specific preoperative evaluation using an adapted index. Omental flap techniques to prevent a postpancreatectomy haemorrhage should be efficient. Effects of preoperative octreotid to harden the pancreas should be clarified.","Source":"PubMed","category":"HUMAN","training_data":"Predictive factors of severe complications for ampullary, bile duct and duodenal cancers following pancreaticoduodenectomy: Multivariate analysis of a 10-year multicentre retrospective series BACKGROUND: Postoperative outcomes following pancreaticoduodenectomy are well described for pancreatic cancers. Due to a lower incidence rate, complication rates and relative predictive factors are less detailed for ampullary, bile duct and duodenal cancers. METHODS: Medical charts of patients operated on between 2001 and 2011 for an ampullary, bile duct or duodenal cancer were reviewed. Data were retrospectively studied with respect to demographics, surgical management, postoperative complications and histological findings. Specific complication rates were reported, and predictive factors for severe morbidity and mortality were determined by multivariate analysis. RESULTS: 135 patients were identified: 55 ampullary, 55 bile duct and 25 duodenal cancers. Twelve patients (8.9%) deceased postoperatively, and 36 others (26.7%) presented severe complications. Sixty-seven percent of the pancreas was soft, and pancreatic hardness was found to be the main protective factor against severe morbidity (HR = 0.36, 95% CI = 0.14-0.94, P = 0.037). Age and postpancreatectomy haemorrhage were independent predictors for death (HR = 14.63, 95% CI = 1.57-135.77, P = 0.018, and HR = 14.71, 95% CI = 2.86-75.62, P = 0.001, respectively). Only the use of an external transanastomotic duct stent significantly reduced both the morbidity (HR = 0.37, 95% CI = 0.16-0.83, P = 0.016), and the mortality (HR = 0.12, 95% CI = 0.02-0.69, P = 0.017). CONCLUSIONS: Pancreaticoduodenectomy for ampullary, bile duct and duodenal cancers is a high-risk procedure. The systematic use of transanastomotic duct stents would significantly decrease the complication rate. Older patients should beneficiate from specific preoperative evaluation using an adapted index. Omental flap techniques to prevent a postpancreatectomy haemorrhage should be efficient. Effects of preoperative octreotid to harden the pancreas should be clarified. PubMed","prediction_labels":"HUMAN"},{"cleaned":"imaging biomarker assessing hepatic function patients primary sclerosing cholangitis background aims aimed evaluate potential hepatobiliary phase magnetic resonance imaging mri parameter assessment hepatocellular function patients primary sclerosing cholangitis psc methods collected data 111 patients 83 male 28 female median 44 years old march 2012 march 2016 confirmed diagnosis psc underwent mri evaluation injection hepatobiliary phase hepatocyte specific contrast agent gadoxetate disodium signal intensities measured liver segment mean relative enhancement values calculated correlated findings liver functions tests prognostic scoring systems model end stage liver disease meld score mayo risk score amsterdam oxford psc score abnormalities detected endoscopic retrograde cholangiopancreatography using amsterdam cholangiographic classification system clinical endpoints liver transplantation cholangiocarcinoma liver related death primary aim associate relative enhancement values liver function patient outcomes results patients moderate stage disease intermediate levels risk median meld score 8 median mayo score 0 27 clinical endpoints reached 21 patients 6 developed cholangiocarcinoma 8 underwent liver transplantation 7 patients died highest levels correlations observed relative enhancement 20 min contrast injection level alkaline phosphatase r 0 636 bilirubin r 0 646 albumin r 0 538 well international normalized ratio r 0 456 meld score r 0 587 mayo risk score r 0 535 amsterdam oxford model score r 0 595 p 0001 relative enhancement correlated clinical endpoints p 05 cutoff relative enhancement value 0 65 identified patients clinical endpoint 73 9 sensitivity 92 9 specificity area receiver operating characteristic curve 0 901 likelihood ratio 10 34 p 0001 conclusions analysis 111 patients psc found mri measured relative enhancement using hepatocyte specific contrast agent identify patients clinical outcomes 73 9 sensitivity 92 9 specificity long term multicenter studies needed evaluate marker psc progression stn","probabilities":0.9799733,"Title":"An Imaging Biomarker For Assessing Hepatic Function In Patients With Primary Sclerosing Cholangitis","Abstract":"Background & aims: We aimed to evaluate the potential of hepatobiliary phase magnetic resonance imaging (MRI) as parameter for assessment of hepatocellular function in patients with primary sclerosing cholangitis (PSC). \r\n\r\n Methods: We collected data from 111 patients (83 male, 28 female; median, 44 years old), from March 2012 through March 2016, with a confirmed diagnosis of PSC who underwent MRI evaluation before and after injection (hepatobiliary phase) of a hepatocyte-specific contrast agent (gadoxetate disodium). Signal intensities were measured in each liver segment. Mean relative enhancement values were calculated and correlated with findings from liver functions tests, prognostic scoring systems (model for end-stage liver disease [MELD] score; Mayo risk score; Amsterdam-Oxford-PSC score), abnormalities detected by endoscopic retrograde cholangiopancreatography (using the Amsterdam cholangiographic classification system), and clinical endpoints (liver transplantation, cholangiocarcinoma, liver-related death). Our primary aim was to associate relative enhancement values with liver function and patient outcomes. \r\n\r\n Results: Most patients had moderate-stage disease and had intermediate levels of risk (median MELD score, 8 and median Mayo score, 0.27). Clinical endpoints were reached by 21 patients (6 developed cholangiocarcinoma, 8 underwent liver transplantation, and 7 patients died). The highest levels of correlations were observed for relative enhancement 20 min after contrast injection and level of alkaline phosphatase (r = -0.636), bilirubin (r = -0.646), albumin (r = 0.538); as well as international normalized ratio (r = 0.456); MELD score (r = -0.587); Mayo risk score (r = -0.535), and Amsterdam-Oxford model score (r = -0.595) (P < .0001). Relative enhancement correlated with all clinical endpoints (all P < .05). A cutoff relative enhancement value of 0.65 identified patients with a clinical endpoint with 73.9% sensitivity 92.9% specificity (area under the receiver operating characteristic curve, 0.901; likelihood ratio, 10.34; P < .0001). \r\n\r\n Conclusions: In an analysis of 111 patients with PSC, we found MRI-measured relative enhancement, using a hepatocyte-specific contrast agent, to identify patients with clinical outcomes with 73.9% sensitivity 92.9% specificity. Long-term, multicenter studies are needed to further evaluate this marker of PSC progression.","Source":"STN","category":"HUMAN","training_data":"An Imaging Biomarker For Assessing Hepatic Function In Patients With Primary Sclerosing Cholangitis Background & aims: We aimed to evaluate the potential of hepatobiliary phase magnetic resonance imaging (MRI) as parameter for assessment of hepatocellular function in patients with primary sclerosing cholangitis (PSC). \r\n\r\n Methods: We collected data from 111 patients (83 male, 28 female; median, 44 years old), from March 2012 through March 2016, with a confirmed diagnosis of PSC who underwent MRI evaluation before and after injection (hepatobiliary phase) of a hepatocyte-specific contrast agent (gadoxetate disodium). Signal intensities were measured in each liver segment. Mean relative enhancement values were calculated and correlated with findings from liver functions tests, prognostic scoring systems (model for end-stage liver disease [MELD] score; Mayo risk score; Amsterdam-Oxford-PSC score), abnormalities detected by endoscopic retrograde cholangiopancreatography (using the Amsterdam cholangiographic classification system), and clinical endpoints (liver transplantation, cholangiocarcinoma, liver-related death). Our primary aim was to associate relative enhancement values with liver function and patient outcomes. \r\n\r\n Results: Most patients had moderate-stage disease and had intermediate levels of risk (median MELD score, 8 and median Mayo score, 0.27). Clinical endpoints were reached by 21 patients (6 developed cholangiocarcinoma, 8 underwent liver transplantation, and 7 patients died). The highest levels of correlations were observed for relative enhancement 20 min after contrast injection and level of alkaline phosphatase (r = -0.636), bilirubin (r = -0.646), albumin (r = 0.538); as well as international normalized ratio (r = 0.456); MELD score (r = -0.587); Mayo risk score (r = -0.535), and Amsterdam-Oxford model score (r = -0.595) (P < .0001). Relative enhancement correlated with all clinical endpoints (all P < .05). A cutoff relative enhancement value of 0.65 identified patients with a clinical endpoint with 73.9% sensitivity 92.9% specificity (area under the receiver operating characteristic curve, 0.901; likelihood ratio, 10.34; P < .0001). \r\n\r\n Conclusions: In an analysis of 111 patients with PSC, we found MRI-measured relative enhancement, using a hepatocyte-specific contrast agent, to identify patients with clinical outcomes with 73.9% sensitivity 92.9% specificity. Long-term, multicenter studies are needed to further evaluate this marker of PSC progression. STN","prediction_labels":"HUMAN"},{"cleaned":"predictors unresectable proximal cholangiocarcinoma potentially resectable patients background although advanced imaging technique used nowadays unresectable rate cholangiocarcinoma 38 patients undergone exploration sub radiological metastases objective identify predictors unresectable proximal cholangiocarcinoma era modern imaging materials methods january 2012 april 2017 patients potentially curative resection underwent laparotomy proximal cholangiocarcinoma evaluated 60 patients categorized two groups resectable unresectable group results intrahepatic cholangiocarcinoma icc group 18 unresectable 27 resectable patients significantly higher levels alkaline phosphatase alp 328 4 versus 148 8 u l p 0 002 gamma glutamyl transferase ggt 364 1 versus 179 9u l p 0 015 higher number patients n2 enlarged lymph nodes ln greater 1 cm imaging 27 8 versus 0 p 0 004 unresectable group perihilar cholangiocarcinoma phc group 5 unresectable 10 resectable patients higher number patients n2 enlarged ln greater 1 cm imaging 40 0 versus 0 p 0 032 unresectable group according univariate analysis alp ggt resectable group unresectable group significantly different using cut level alp 150 u l odds ratio 0 240 p 0 028 ggt level 240 u l odds ratio 0 154 p 0 005 ggt one independent predictor using cut level 240 u l odds ratio 0 154 p 0 13 area receiver operating characteristic roc curve ggt 0 7127 conclusion ggt moderate powerful predictor unresectable patients icc patients high serum level ggt 240 u l google scholar","probabilities":0.9799733,"Title":"Predictors Of Unresectable Proximal Cholangiocarcinoma In Potentially Resectable Patients","Abstract":"Background: Although advanced imaging technique is being used nowadays, the unresectable rate of cholangiocarcinoma has been 38% in patients who have undergone exploration because of sub-radiological metastases. Objective: To identify the predictors of unresectable proximal cholangiocarcinoma in era of modern imaging. Materials and Methods: Between January 2012 and April 2017, patients who had potentially curative resection and underwent laparotomy for proximal cholangiocarcinoma were evaluated. The 60 patients were categorized into two groups, resectable and unresectable group. Results: For an intrahepatic cholangiocarcinoma [ICC] group of 18-unresectable and 27-resectable patients, there were significantly higher levels of alkaline phosphatase [ALP] (328.4 versus 148.8 U/L, p = 0.002), gamma-glutamyl transferase [GGT] (364.1 versus 179.9U/L, p = 0.015) and a higher number of patients with N2-enlarged lymph nodes [LN] greater than 1 cm from imaging (27.8% versus 0%, p = 0.004) in unresectable group. For a perihilar cholangiocarcinoma [PHC] group of 5-unresectable and 10-resectable patients, there was a higher number of patients with N2-enlarged LN greater than 1 cm from imaging (40.0% versus 0%, p = 0.032) in unresectable group. According to univariate analysis, ALP and GGT of resectable group and unresectable group were significantly different by using cut-off level of ALP at 150 U/L (odds ratio 0.240, p = 0.028) and GGT level at 240 U/L (odds ratio 0.154, p = 0.005). The GGT was the only one independent predictor by using cut-off level at 240 U/L (odds ratio 0.154, p = 0.13). The area under the receiver operating characteristic [ROC] curve of GGT was 0.7127. Conclusion: The GGT was the moderate powerful predictor of unresectable patients for ICC in patients with high a serum level of GGT more than 240 U/L.","Source":"Google Scholar","category":"HUMAN","training_data":"Predictors Of Unresectable Proximal Cholangiocarcinoma In Potentially Resectable Patients Background: Although advanced imaging technique is being used nowadays, the unresectable rate of cholangiocarcinoma has been 38% in patients who have undergone exploration because of sub-radiological metastases. Objective: To identify the predictors of unresectable proximal cholangiocarcinoma in era of modern imaging. Materials and Methods: Between January 2012 and April 2017, patients who had potentially curative resection and underwent laparotomy for proximal cholangiocarcinoma were evaluated. The 60 patients were categorized into two groups, resectable and unresectable group. Results: For an intrahepatic cholangiocarcinoma [ICC] group of 18-unresectable and 27-resectable patients, there were significantly higher levels of alkaline phosphatase [ALP] (328.4 versus 148.8 U/L, p = 0.002), gamma-glutamyl transferase [GGT] (364.1 versus 179.9U/L, p = 0.015) and a higher number of patients with N2-enlarged lymph nodes [LN] greater than 1 cm from imaging (27.8% versus 0%, p = 0.004) in unresectable group. For a perihilar cholangiocarcinoma [PHC] group of 5-unresectable and 10-resectable patients, there was a higher number of patients with N2-enlarged LN greater than 1 cm from imaging (40.0% versus 0%, p = 0.032) in unresectable group. According to univariate analysis, ALP and GGT of resectable group and unresectable group were significantly different by using cut-off level of ALP at 150 U/L (odds ratio 0.240, p = 0.028) and GGT level at 240 U/L (odds ratio 0.154, p = 0.005). The GGT was the only one independent predictor by using cut-off level at 240 U/L (odds ratio 0.154, p = 0.13). The area under the receiver operating characteristic [ROC] curve of GGT was 0.7127. Conclusion: The GGT was the moderate powerful predictor of unresectable patients for ICC in patients with high a serum level of GGT more than 240 U/L. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological assessment cholangiocarcinoma tertiary cancer centre period 4 years introduction nearly 1000 people diagnosed bile duct cancer year great britain radical surgery remains optimal therapy cholangiocarcinoma o ering potential cure present study conducted assess adverse prognostic factors associated cancers methods operable cases cholangiocarcinomas period four years 2012 2015 tertiary cancer centre identi ed winpath histology database histology slides reviewed cases classi ed basis location intrapancreatic extra hepatic biliary tree intrahepatic cancers various adverse prognostic factors assessed clinical information wherever possible obtained medical records results 41 cases reported cholangiocarcinomas 3 cases excluded study n 38 male female ratio 4 1 11 cases 29 extra hepatic biliary tree 18 cases 47 intrapancreatic 9 cases 24 intrahepatic origin common histology grade 3 adenocarcinoma 29 cases 14 18 78 intrapancreatic cholangiocarcinoma lymph node metastasis 18 higher stage t3 presentation overall mortality rate 37 14 38 cases slightly higher advanced stage pt3 intrapancreatic cancers 7 18 cases conclusion intrapancreatic location cholangiocarcinoma common present study high mortality rate associated advanced stage lymph node metastasis google scholar","probabilities":0.9799733,"Title":"Clinicopathological Assessment Of Cholangiocarcinoma In A Tertiary Cancer Centre Over A Period Of 4 Years","Abstract":"Introduction: Nearly 1000 people are diagnosed with bile duct cancer each year in Great Britain. Radical surgery remains the optimal therapy for cholangiocarcinoma, oering potential cure. The present study was conducted to assess the adverse prognostic factors associated with these cancers. Methods: All operable cases of cholangiocarcinomas over a period of four years (2012-2015) in a tertiary cancer centre were identied on the Winpath histology database. Histology slides were reviewed and cases were classied on the basis of location into intrapancreatic, extra hepatic biliary tree and intrahepatic cancers. Various adverse prognostic factors were assessed. Clinical information wherever possible was obtained from medical records. Results: Out of 41 cases reported as cholangiocarcinomas, 3 cases were excluded from the study (n=38). The male to female ratio was 4:1. 11 cases (29%) were in the extra hepatic biliary tree, 18 cases (47%) were intrapancreatic and 9 cases (24%) were intrahepatic in origin. The most common histology was grade 3 adenocarcinoma (29 cases). 14/18 (78%) intrapancreatic cholangiocarcinoma had lymph node metastasis and all 18 had higher stage (T3) at presentation. The overall mortality rate was 37 % (14/38 cases) and was slightly higher in advanced stage (pT3) intrapancreatic cancers (7/18 cases). Conclusion: Intrapancreatic location of cholangiocarcinoma was most common in present study and a high mortality rate was associated with advanced stage and lymph node metastasis.","Source":"Google Scholar","category":"HUMAN","training_data":"Clinicopathological Assessment Of Cholangiocarcinoma In A Tertiary Cancer Centre Over A Period Of 4 Years Introduction: Nearly 1000 people are diagnosed with bile duct cancer each year in Great Britain. Radical surgery remains the optimal therapy for cholangiocarcinoma, oering potential cure. The present study was conducted to assess the adverse prognostic factors associated with these cancers. Methods: All operable cases of cholangiocarcinomas over a period of four years (2012-2015) in a tertiary cancer centre were identied on the Winpath histology database. Histology slides were reviewed and cases were classied on the basis of location into intrapancreatic, extra hepatic biliary tree and intrahepatic cancers. Various adverse prognostic factors were assessed. Clinical information wherever possible was obtained from medical records. Results: Out of 41 cases reported as cholangiocarcinomas, 3 cases were excluded from the study (n=38). The male to female ratio was 4:1. 11 cases (29%) were in the extra hepatic biliary tree, 18 cases (47%) were intrapancreatic and 9 cases (24%) were intrahepatic in origin. The most common histology was grade 3 adenocarcinoma (29 cases). 14/18 (78%) intrapancreatic cholangiocarcinoma had lymph node metastasis and all 18 had higher stage (T3) at presentation. The overall mortality rate was 37 % (14/38 cases) and was slightly higher in advanced stage (pT3) intrapancreatic cancers (7/18 cases). Conclusion: Intrapancreatic location of cholangiocarcinoma was most common in present study and a high mortality rate was associated with advanced stage and lymph node metastasis. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"development evaluation pcr methods based cytochrome c oxidase subunit one cox1 nadh dehydrogenase subunit one gene nad1 detect opisthorchis viverrini human fecal samples opisthorchis viverrini highly prevalent throughout southeast asia chronic infection parasite leads cholangiocarcinoma cca fatal bile duct cancer early accurate detection parasite important therefore new pcr methods targeting cytochrome c oxidase subunit one nadh dehydrogenase subunit one gene detect o viverrini fecal specimens developed ninety o viverrini positive human fecal samples used study pcr sensitivity genes compared internal transcribe spacer 2 its2 pcr sensitivity cox1 pcr nad1 pcr 66 7 50 respectively sensitivity cox1 pcr nad1 pcr achieved 89 1 71 7 specimens containing o viverrini eggs 100 eggs per gram epg additionally primers used provide information genetic diversity mitochondrial genes o viverrini stn","probabilities":1.0,"Title":"Development And Evaluation Of Pcr Methods Based On Cytochrome C Oxidase Subunit One (Cox1) And Nadh Dehydrogenase Subunit One Gene (Nad1) To Detect Opisthorchis Viverrini In Human Fecal Samples","Abstract":"Opisthorchis viverrini is highly prevalent throughout Southeast Asia. Chronic infection of this parasite leads to cholangiocarcinoma (CCA), a fatal bile duct cancer. The early and accurate detection of this parasite is very important; therefore, new PCR methods targeting cytochrome c oxidase subunit one and NADH dehydrogenase subunit one gene to detect O. viverrini in fecal specimens have been developed. Ninety O. viverrini-positive human fecal samples were used in this study. The PCR sensitivity of both genes was compared with internal transcribe spacer 2 (ITS2)-PCR. The sensitivity of cox1-PCR and nad1-PCR was 66.7 and 50 %, respectively. The sensitivity of cox1-PCR and nad1-PCR achieved 89.1 and 71.7 % in specimens containing O. viverrini eggs of >100 eggs per gram (EPG). Additionally, these primers can be used to provide the information on genetic diversity from mitochondrial genes of O. viverrini.","Source":"STN","category":"ANIMAL","training_data":"Development And Evaluation Of Pcr Methods Based On Cytochrome C Oxidase Subunit One (Cox1) And Nadh Dehydrogenase Subunit One Gene (Nad1) To Detect Opisthorchis Viverrini In Human Fecal Samples Opisthorchis viverrini is highly prevalent throughout Southeast Asia. Chronic infection of this parasite leads to cholangiocarcinoma (CCA), a fatal bile duct cancer. The early and accurate detection of this parasite is very important; therefore, new PCR methods targeting cytochrome c oxidase subunit one and NADH dehydrogenase subunit one gene to detect O. viverrini in fecal specimens have been developed. Ninety O. viverrini-positive human fecal samples were used in this study. The PCR sensitivity of both genes was compared with internal transcribe spacer 2 (ITS2)-PCR. The sensitivity of cox1-PCR and nad1-PCR was 66.7 and 50 %, respectively. The sensitivity of cox1-PCR and nad1-PCR achieved 89.1 and 71.7 % in specimens containing O. viverrini eggs of >100 eggs per gram (EPG). Additionally, these primers can be used to provide the information on genetic diversity from mitochondrial genes of O. viverrini. STN","prediction_labels":"ANIMAL"},{"cleaned":"incidental gallbladder cancer cholecystectomy surgeon suspicious background preoperative predictors incidental gallbladder cancer igbc poorly defined despite frequency cholecystectomy performed objective study define incidence consider risk factors igbc cholecystectomy methods american college surgeons national surgical quality improvement program acs nsqip database 2005 2009 used identify patients underwent cholecystectomy n 91 260 patients international classification diseases ninth revision diagnosis gallbladder malignancy underwent laparoscopic cholecystectomy lc n 80 924 open cholecystectomy oc n 10 336 alone included results incidence igbc 0 19 n 170 cholecystectomy cases 0 05 lc 0 60 lc converted oc p 0 001 vs lc 1 13 oc p 0 001 vs others patients undergoing oc 17 3 times likely igbc lc patients age 65 years older asian african american race asa american society anesthesiologists class 3 diabetes mellitus hypertension weight loss 10 alkaline phosphatase levels 120 units l albumin levels 3 6 g dl less associated igbc multiple logistic regression identified oc age 65 years older asian african american race elevated alkaline phosphatase level female sex independent risk factors patients 1 2 3 4 factors 6 3 16 7 30 0 47 4 fold risk igbc respectively zero risk factor baseline 0 03 conclusions surgeons suspicion gbc heightened performing converting lc oc patients older asian african american female elevated alkaline phosphatase level pubmed","probabilities":0.9799733,"Title":"Incidental gallbladder cancer at cholecystectomy: when should the surgeon be suspicious?","Abstract":"BACKGROUND: Preoperative predictors of incidental gallbladder cancer (iGBC) have been poorly defined despite the frequency with which cholecystectomy is performed. The objective of this study was to define the incidence of and consider risk factors for iGBC at cholecystectomy. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2009) was used to identify all patients who underwent cholecystectomy (N = 91,260). Patients with an International Classification of Diseases, Ninth Revision, diagnosis of gallbladder malignancy who underwent a laparoscopic cholecystectomy (LC; n = 80,924) or open cholecystectomy (OC; n = 10,336) alone were included. RESULTS: The incidence of iGBC was 0.19% (n = 170) for all cholecystectomy cases, but 0.05% at LC, 0.60% at LC converted to OC (P < 0.001 vs LC), and 1.13% at OC (P < 0.001 vs others). Patients undergoing OC were 17.3 times more likely to have iGBC than LC patients. Age 65 years or older, Asian or African American race, ASA (American Society of Anesthesiologists) class 3 or more, diabetes mellitus, hypertension, weight loss more than 10%, alkaline phosphatase levels 120 units/L or more, and albumin levels 3.6 g/dL or less were associated with iGBC. Multiple logistic regression identified having an OC, age 65 years or older, Asian or African American race, an elevated alkaline phosphatase level, and female sex as independent risk factors. Patients with 1, 2, 3, and 4 of these factors had a 6.3-, 16.7-, 30.0-, and 47.4-fold risk of iGBC, respectively, from a zero-risk factor baseline of 0.03%. CONCLUSIONS: Surgeons' suspicion for GBC should be heightened when they are performing or converting from LC to OC and when patients are older, Asian or African American, female, and have an elevated alkaline phosphatase level.","Source":"PubMed","category":"HUMAN","training_data":"Incidental gallbladder cancer at cholecystectomy: when should the surgeon be suspicious? BACKGROUND: Preoperative predictors of incidental gallbladder cancer (iGBC) have been poorly defined despite the frequency with which cholecystectomy is performed. The objective of this study was to define the incidence of and consider risk factors for iGBC at cholecystectomy. METHODS: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2009) was used to identify all patients who underwent cholecystectomy (N = 91,260). Patients with an International Classification of Diseases, Ninth Revision, diagnosis of gallbladder malignancy who underwent a laparoscopic cholecystectomy (LC; n = 80,924) or open cholecystectomy (OC; n = 10,336) alone were included. RESULTS: The incidence of iGBC was 0.19% (n = 170) for all cholecystectomy cases, but 0.05% at LC, 0.60% at LC converted to OC (P < 0.001 vs LC), and 1.13% at OC (P < 0.001 vs others). Patients undergoing OC were 17.3 times more likely to have iGBC than LC patients. Age 65 years or older, Asian or African American race, ASA (American Society of Anesthesiologists) class 3 or more, diabetes mellitus, hypertension, weight loss more than 10%, alkaline phosphatase levels 120 units/L or more, and albumin levels 3.6 g/dL or less were associated with iGBC. Multiple logistic regression identified having an OC, age 65 years or older, Asian or African American race, an elevated alkaline phosphatase level, and female sex as independent risk factors. Patients with 1, 2, 3, and 4 of these factors had a 6.3-, 16.7-, 30.0-, and 47.4-fold risk of iGBC, respectively, from a zero-risk factor baseline of 0.03%. CONCLUSIONS: Surgeons' suspicion for GBC should be heightened when they are performing or converting from LC to OC and when patients are older, Asian or African American, female, and have an elevated alkaline phosphatase level. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic biomarkers cholangiocarcinoma clinical implications cholangiocarcinoma cca poorly prognostic cancer limited treatment options patients unresectable tumors diagnosed chemotherapies provided limited benefit prognostic markers therefore necessary predict disease outcome risk relapse suggest best treatment option areas covered article provides date review biomarkers promising characteristics prognostic markers cca reported past 5 years biomarkers sub classified tissue serum markers proteins rnas peripheral blood cells etc associated aggressive phenotypes signal pathways chemo drug resistance reflect survival time cca patients evaluated prognostic prediction values expert commentary ccas heterogeneous tumors different histo pathological subtypes genetic influences therefore potential markers validated larger collectives varied epidemiological backgrounds systematic review meta analysis done clarify impact reported biomolecules potential prognostic values non low invasive sample collections well simple affordable determination methods constructed make prognostic biomarkers available clinical practice pubmed","probabilities":0.7966102,"Title":"Prognostic biomarkers for cholangiocarcinoma and their clinical implications","Abstract":"Cholangiocarcinoma (CCA) is a poorly prognostic cancer with limited treatment options. Most patients have unresectable tumors when they are diagnosed and the chemotherapies provided are of limited benefit. Prognostic markers are therefore necessary to predict the disease outcome, risk of relapse, or to suggest the best treatment option. Areas covered: This article provides an up-to-date review of biomarkers with promising characteristics to be prognostic markers for CCA reported in the past 5 years. The biomarkers are sub-classified into tissue and serum markers. Proteins, RNAs, peripheral blood cells etc., that are associated with aggressive phenotypes, signal pathways, chemo-drug resistance, and those that reflect the survival time of CCA patients are evaluated for their prognostic prediction values. Expert commentary: CCAs are heterogeneous tumors of different histo-pathological subtypes and genetic influences and, therefore, potential markers should be validated in larger collectives with varied epidemiological backgrounds. A systematic review and meta-analysis should be done to clarify the impact of the reported biomolecules for their potential prognostic values. Non- or low-invasive sample collections, as well as the simple and affordable determination methods, should be constructed to make the prognostic biomarkers available in clinical practice.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic biomarkers for cholangiocarcinoma and their clinical implications Cholangiocarcinoma (CCA) is a poorly prognostic cancer with limited treatment options. Most patients have unresectable tumors when they are diagnosed and the chemotherapies provided are of limited benefit. Prognostic markers are therefore necessary to predict the disease outcome, risk of relapse, or to suggest the best treatment option. Areas covered: This article provides an up-to-date review of biomarkers with promising characteristics to be prognostic markers for CCA reported in the past 5 years. The biomarkers are sub-classified into tissue and serum markers. Proteins, RNAs, peripheral blood cells etc., that are associated with aggressive phenotypes, signal pathways, chemo-drug resistance, and those that reflect the survival time of CCA patients are evaluated for their prognostic prediction values. Expert commentary: CCAs are heterogeneous tumors of different histo-pathological subtypes and genetic influences and, therefore, potential markers should be validated in larger collectives with varied epidemiological backgrounds. A systematic review and meta-analysis should be done to clarify the impact of the reported biomolecules for their potential prognostic values. Non- or low-invasive sample collections, as well as the simple and affordable determination methods, should be constructed to make the prognostic biomarkers available in clinical practice. PubMed","prediction_labels":"HUMAN"},{"cleaned":"influence mtor inhibitors mycophenolic acid human cholangiocellular carcinoma cancer associated fibroblasts background incidence cholangiocellular carcinoma cca increasing western world tumour high proportion desmoplastic stroma correlated worse prognosis cancer associated myofibroblasts cafs present recent studies showed promising results liver transplantation ltx non resectable early stage cca mycophenolic acid mpa mtor inhibitor everolimus used prevent organ rejection recently shown exhibit antiproliferative effect cca cells little known influence immunosuppressive drugs tumour cell proliferation migration paracrine stimulation cafs moreover still unknown signaling pathways activated following specific cell cell interactions methods cca cell lines hucct1 tfk1 utilized study cafs derived resected cca cancer tissue cell viability measured crystal violet assay tumour cell invasion quantified using modified co culture transmigration assay semiquantitative cytokine expression measured using cytokine array protein expression phosphorylation erk stat3 akt determined western blot analysis results cca cells treated mpa exhibited dose related decrease cell viability contrast cyclosporine csa treatment effect cell viability everolimus significantly inhibited proliferation low concentrations pro invasive effect cafs co culture transmigration assay significantly reduced everolimus concentration 1nm p 0 047 contrast mpa csa showed effect tumour cell invasion treatment cafs 1nm everolimus showed significant reduction expression il 8 il 13 mcp1 mif serpin e1 cca cells showed significant increases phosphorylation erk stat3 akt influence conditioned caf media effect suppressed everolimus conclusions secretion proinflammatory cytokines cafs may lead increased activation jak stat3 erk akt signaling increased migration cca cells everolimus abrogates effect inhibits proliferation cca cells even low concentrations ltx non resectable early stage cca currently performed several clinical studies consistent role common immunosuppressants inhibiting tumour cell proliferation invasion study indicates combination standard therapies everolimus mpa promising therapy option treat cca following ltx stn","probabilities":0.9467213,"Title":"Influence Of Mtor-Inhibitors And Mycophenolic Acid On Human Cholangiocellular Carcinoma And Cancer Associated Fibroblasts","Abstract":"Background: The incidence of Cholangiocellular Carcinoma (CCA) is increasing in the western world. The tumour has a high proportion of desmoplastic stroma and is correlated with a worse prognosis when cancer associated myofibroblasts (CAFs) are present. Recent studies showed promising results after liver transplantation (LTx) in non-resectable early stage CCA. Mycophenolic acid (MPA) and the mTor inhibitor Everolimus are used to prevent organ rejection but recently were shown to exhibit an antiproliferative effect on CCA-cells. Little is known about the influence of immunosuppressive drugs on tumour cell proliferation and migration after paracrine stimulation by CAFs. Moreover, it is still unknown, which signaling pathways are activated following these specific cell-cell interactions. \r\n\r\n Methods: CCA cell lines HuCCT1 and TFK1 were utilized for the study. CAFs were derived from resected CCA cancer tissue. Cell viability was measured by the crystal violet assay and tumour cell invasion was quantified using a modified co-culture transmigration assay. Semiquantitative cytokine-expression was measured using a cytokine-array. Protein expression and phosphorylation of ERK, STAT3 and AKT was determined by Western-blot analysis. \r\n\r\n Results: CCA cells treated with MPA exhibited a dose related decrease in cell viability in contrast to Cyclosporine A (CSA) treatment which had no effect on cell viability. Everolimus significantly inhibited proliferation at very low concentrations. The pro-invasive effect of CAFs in co-culture transmigration assay was significantly reduced by Everolimus at a concentration of 1nM (p = 0.047). In contrast, MPA and CSA showed no effect on tumour cell invasion. Treatment of CAFs with 1nM Everolimus showed a significant reduction in the expression of IL 8, IL 13, MCP1, MIF and Serpin E1. CCA-cells showed significant increases in phosphorylation of ERK, STAT3 and AKT under the influence of conditioned CAF-media. This effect was suppressed by Everolimus. \r\n\r\n Conclusions: The secretion of proinflammatory cytokines by CAFs may lead to increased activation of JAK/STAT3-, ERK- and AKT-signaling and increased migration of CCA-cells. Everolimus abrogates this effect and inhibits proliferation of CCA-cells even at low concentrations. LTx for non-resectable early stage CCA is currently performed in several clinical studies. Consistent with a role for common immunosuppressants in inhibiting tumour cell-proliferation and -invasion, our study indicates that a combination of standard therapies with Everolimus and MPA is a promising therapy option to treat CCA following LTx.","Source":"STN","category":"ANIMAL","training_data":"Influence Of Mtor-Inhibitors And Mycophenolic Acid On Human Cholangiocellular Carcinoma And Cancer Associated Fibroblasts Background: The incidence of Cholangiocellular Carcinoma (CCA) is increasing in the western world. The tumour has a high proportion of desmoplastic stroma and is correlated with a worse prognosis when cancer associated myofibroblasts (CAFs) are present. Recent studies showed promising results after liver transplantation (LTx) in non-resectable early stage CCA. Mycophenolic acid (MPA) and the mTor inhibitor Everolimus are used to prevent organ rejection but recently were shown to exhibit an antiproliferative effect on CCA-cells. Little is known about the influence of immunosuppressive drugs on tumour cell proliferation and migration after paracrine stimulation by CAFs. Moreover, it is still unknown, which signaling pathways are activated following these specific cell-cell interactions. \r\n\r\n Methods: CCA cell lines HuCCT1 and TFK1 were utilized for the study. CAFs were derived from resected CCA cancer tissue. Cell viability was measured by the crystal violet assay and tumour cell invasion was quantified using a modified co-culture transmigration assay. Semiquantitative cytokine-expression was measured using a cytokine-array. Protein expression and phosphorylation of ERK, STAT3 and AKT was determined by Western-blot analysis. \r\n\r\n Results: CCA cells treated with MPA exhibited a dose related decrease in cell viability in contrast to Cyclosporine A (CSA) treatment which had no effect on cell viability. Everolimus significantly inhibited proliferation at very low concentrations. The pro-invasive effect of CAFs in co-culture transmigration assay was significantly reduced by Everolimus at a concentration of 1nM (p = 0.047). In contrast, MPA and CSA showed no effect on tumour cell invasion. Treatment of CAFs with 1nM Everolimus showed a significant reduction in the expression of IL 8, IL 13, MCP1, MIF and Serpin E1. CCA-cells showed significant increases in phosphorylation of ERK, STAT3 and AKT under the influence of conditioned CAF-media. This effect was suppressed by Everolimus. \r\n\r\n Conclusions: The secretion of proinflammatory cytokines by CAFs may lead to increased activation of JAK/STAT3-, ERK- and AKT-signaling and increased migration of CCA-cells. Everolimus abrogates this effect and inhibits proliferation of CCA-cells even at low concentrations. LTx for non-resectable early stage CCA is currently performed in several clinical studies. Consistent with a role for common immunosuppressants in inhibiting tumour cell-proliferation and -invasion, our study indicates that a combination of standard therapies with Everolimus and MPA is a promising therapy option to treat CCA following LTx. STN","prediction_labels":"ANIMAL"},{"cleaned":"fibroblast growth factor receptor 2 fusions target treating cholangiocarcinoma purpose review review cover role fibroblast growth factor pathway pathogenesis targeted therapy potential prognostic value patients cholangiocarcinoma cca recent findings recent studies identified fibroblast growth factor receptor 2 fgfr2 fusions prognostic implications fgfr2 fusions treatment strategies target fgfr2 cca future directions understanding targeting fgfr2 pathway disease discussed summary understanding role fgfr2 pathway disease pathogenetic mechanism ability develop targeted therapies diagnostics surrounding concept critical elements toward developing novel targeted approaches cca pubmed","probabilities":0.9799733,"Title":"Fibroblast growth factor receptor 2 fusions as a target for treating cholangiocarcinoma","Abstract":"PURPOSE OF REVIEW: This review will cover the role of the fibroblast growth factor pathway in the pathogenesis, targeted therapy potential and prognostic value in patients with cholangiocarcinoma (CCA). RECENT FINDINGS: Recent studies that have identified fibroblast growth factor receptor 2 (FGFR2) fusions, prognostic implications of FGFR2 fusions, treatment strategies that target FGFR2 in CCA and future directions for understanding and targeting the FGFR2 pathway in this disease, will be discussed. SUMMARY: Understanding the role of the FGFR2 pathway as a disease pathogenetic mechanism and the ability to develop targeted therapies and diagnostics surrounding this concept are critical elements toward developing novel targeted approaches in CCA.","Source":"PubMed","category":"HUMAN","training_data":"Fibroblast growth factor receptor 2 fusions as a target for treating cholangiocarcinoma PURPOSE OF REVIEW: This review will cover the role of the fibroblast growth factor pathway in the pathogenesis, targeted therapy potential and prognostic value in patients with cholangiocarcinoma (CCA). RECENT FINDINGS: Recent studies that have identified fibroblast growth factor receptor 2 (FGFR2) fusions, prognostic implications of FGFR2 fusions, treatment strategies that target FGFR2 in CCA and future directions for understanding and targeting the FGFR2 pathway in this disease, will be discussed. SUMMARY: Understanding the role of the FGFR2 pathway as a disease pathogenetic mechanism and the ability to develop targeted therapies and diagnostics surrounding this concept are critical elements toward developing novel targeted approaches in CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical combined treatment patients cholangiocellular carcinoma introduction liver resection essential method cholangiocellular carcinoma treatment however due low resectability high incidence recurrences search additional curative methods necessary aim improve results surgical treatment patients cholangiocellular carcinoma especially complications poor prognosis material methods total 95 surgical procedures intrahepatic cholangiocarcinoma performed department liver andpancreatic tumors n n blokhin russian cancer research center since 1998 2014 11 patients obstructive jaundice first symptom disease extended liver resections done cases 84 2 preoperative treatment performed 3 patients adjuvant chemotherapy r0 resection applied 15 patients results postoperative mortality rate 4 2 postoperative complications observed 51 53 7 patients complication grade iii adjuvant chemotherapy observed one 6 7 patient median survival liver resection 25 months 5 year survival rate 25 3 stage ii five year survival reached 66 7 patients obstructive jaundice 5 year survival rate 26 7 median survival 37 months improvement survival case adjuvant therapy conclusion liver resection remains essential treatment cholangiocellular carcinoma including patients obstructive jaundice additional curative methods necessary increase resectability decrease risk recurrence pubmed","probabilities":0.9799733,"Title":"Surgical and combined treatment of patients with cholangiocellular carcinoma","Abstract":"INTRODUCTION: Liver resection is the essential method of cholangiocellular carcinoma treatment. However due to low resectability and high incidence of recurrences search for additional curative methods is necessary. AIM: To improve the results of surgical treatment of patients with cholangiocellular carcinoma especially with complications and poor prognosis. MATERIAL AND METHODS: A total of 95 surgical procedures for intrahepatic cholangiocarcinoma have been performed in the department of liver andpancreatic tumors at N.N. Blokhin Russian Cancer Research Center since 1998 to 2014. 11 patients had obstructive jaundice as the first symptom of the disease. Extended liver resections were done in most cases (84.2%). Preoperative treatment was performed in 3 patients. Adjuvant chemotherapy after R0-resection was applied in 15 patients. RESULTS: The postoperative mortality rate was 4.2%. Postoperative complications were observed in 51 (53.7%) patients. Complication grade III after adjuvant chemotherapy was observed in one (6.7%) patient. Median survival after liver resection was 25 months, 5-year survival rate - 25.3%. In stage I-II five-year survival reached 66.7%. In patients with obstructive jaundice 5-year survival rate was 26.7%, median survival - 37 months. There was no improvement of survival in case of adjuvant therapy. CONCLUSION: Liver resection remains essential treatment of cholangiocellular carcinoma including patients with obstructive jaundice. Additional curative methods are necessary to increase resectability and decrease the risk of recurrence.","Source":"PubMed","category":"HUMAN","training_data":"Surgical and combined treatment of patients with cholangiocellular carcinoma INTRODUCTION: Liver resection is the essential method of cholangiocellular carcinoma treatment. However due to low resectability and high incidence of recurrences search for additional curative methods is necessary. AIM: To improve the results of surgical treatment of patients with cholangiocellular carcinoma especially with complications and poor prognosis. MATERIAL AND METHODS: A total of 95 surgical procedures for intrahepatic cholangiocarcinoma have been performed in the department of liver andpancreatic tumors at N.N. Blokhin Russian Cancer Research Center since 1998 to 2014. 11 patients had obstructive jaundice as the first symptom of the disease. Extended liver resections were done in most cases (84.2%). Preoperative treatment was performed in 3 patients. Adjuvant chemotherapy after R0-resection was applied in 15 patients. RESULTS: The postoperative mortality rate was 4.2%. Postoperative complications were observed in 51 (53.7%) patients. Complication grade III after adjuvant chemotherapy was observed in one (6.7%) patient. Median survival after liver resection was 25 months, 5-year survival rate - 25.3%. In stage I-II five-year survival reached 66.7%. In patients with obstructive jaundice 5-year survival rate was 26.7%, median survival - 37 months. There was no improvement of survival in case of adjuvant therapy. CONCLUSION: Liver resection remains essential treatment of cholangiocellular carcinoma including patients with obstructive jaundice. Additional curative methods are necessary to increase resectability and decrease the risk of recurrence. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder carcinoma cholecystectomy abstract available google scholar","probabilities":0.9799733,"Title":"Incidental Gallbladder Carcinoma After Cholecystectomy","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Incidental Gallbladder Carcinoma After Cholecystectomy Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"human equilibrative nucleoside transporter 1 hent1 expression potential predictive tool response gemcitabine patients advanced cholangiocarcinoma background cholangiocarcinoma cc rare cancer liver surgery offers chance cure surgery unfeasible chemotherapy backbone treatment combined administration cisplatin gemcitabine considered standard care human equilibrative nucleoside transporter 1 hent1 major transporter responsible gemcitabine uptake cells hent1 expression associated increased survival patients receiving gemcitabine pancreatic cancer surgery suggesting hent1 predictive response gemcitabine aim determine whether correlation expression hent1 disease outcome cc methods retrospective study 43 patients treated centre locally advanced metastatic cc received first line treatment gemcitabine performed results whole population median progression free survival pfs overall survival os 4 0 95 confidence interval 2 7 5 3 months 10 0 months 95 ci 6 8 13 2 months respectively 26 samples available hent1 staining 18 69 8 31 patients high low hent1 immunostaining respectively median pfs 2 0 versus 6 0 months low versus high staining respectively p 0 012 median os 5 0 versus 11 0 months low versus high staining respectively p 0 036 multivariate analysis hent1 expression single independent predictive factor associated prolonged pfs hr 0 35 p 0 023 os hr 0 41 p 0 046 conclusion study show potential hent1 expression predictor outcome cc treated gemcitabine larger studies necessary confirm promising results pubmed","probabilities":0.8684211,"Title":"Human equilibrative nucleoside transporter 1 (hENT1) expression is a potential predictive tool for response to gemcitabine in patients with advanced cholangiocarcinoma","Abstract":"BACKGROUND: Cholangiocarcinoma (CC) is a rare cancer of the liver. Surgery offers the only chance for cure. When surgery is unfeasible, chemotherapy is the backbone of treatment. The combined administration of cisplatin and gemcitabine is considered standard of care. Human equilibrative nucleoside transporter 1 (hENT1) is the major transporter responsible for gemcitabine uptake into cells. hENT1 expression is associated with an increased survival for patients receiving gemcitabine after pancreatic cancer surgery, suggesting that hENT1 is predictive of response to gemcitabine. AIM: To determine whether there is a correlation between the expression of hENT1 and disease outcome in CC. METHODS: A retrospective study on 43 patients treated at our centre with a locally advanced or metastatic CC, who received first line treatment with gemcitabine, was performed. RESULTS: For the whole population, median Progression Free Survival (PFS) and overall survival (OS) were 4.0 (95% Confidence Interval 2.7-5.3 months) and 10.0 months (95%CI 6.8-13.2 months), respectively. From the 26 samples available for hENT1 staining, 18 (69%) and 8 (31%) patients had high and low hENT1 immunostaining, respectively. The median PFS were 2.0 versus 6.0 months for low versus high staining respectively (p = 0.012). The median OS were 5.0 versus 11.0 months for low versus high staining, respectively (p = 0.036). On multivariate analysis, hENT1 expression was the single independent predictive factor associated with prolonged PFS (HR 0.35, p = 0.023) and OS (HR 0.41, p = 0.046). CONCLUSION: In this study we show the potential of hENT1 expression as a predictor of outcome in CC treated with gemcitabine. Larger studies are necessary to confirm these promising results.","Source":"PubMed","category":"HUMAN","training_data":"Human equilibrative nucleoside transporter 1 (hENT1) expression is a potential predictive tool for response to gemcitabine in patients with advanced cholangiocarcinoma BACKGROUND: Cholangiocarcinoma (CC) is a rare cancer of the liver. Surgery offers the only chance for cure. When surgery is unfeasible, chemotherapy is the backbone of treatment. The combined administration of cisplatin and gemcitabine is considered standard of care. Human equilibrative nucleoside transporter 1 (hENT1) is the major transporter responsible for gemcitabine uptake into cells. hENT1 expression is associated with an increased survival for patients receiving gemcitabine after pancreatic cancer surgery, suggesting that hENT1 is predictive of response to gemcitabine. AIM: To determine whether there is a correlation between the expression of hENT1 and disease outcome in CC. METHODS: A retrospective study on 43 patients treated at our centre with a locally advanced or metastatic CC, who received first line treatment with gemcitabine, was performed. RESULTS: For the whole population, median Progression Free Survival (PFS) and overall survival (OS) were 4.0 (95% Confidence Interval 2.7-5.3 months) and 10.0 months (95%CI 6.8-13.2 months), respectively. From the 26 samples available for hENT1 staining, 18 (69%) and 8 (31%) patients had high and low hENT1 immunostaining, respectively. The median PFS were 2.0 versus 6.0 months for low versus high staining respectively (p = 0.012). The median OS were 5.0 versus 11.0 months for low versus high staining, respectively (p = 0.036). On multivariate analysis, hENT1 expression was the single independent predictive factor associated with prolonged PFS (HR 0.35, p = 0.023) and OS (HR 0.41, p = 0.046). CONCLUSION: In this study we show the potential of hENT1 expression as a predictor of outcome in CC treated with gemcitabine. Larger studies are necessary to confirm these promising results. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence prevalence survival patients rare epithelial digestive cancers diagnosed europe 1995 2002 background aims little known epidemiology rare epithelial digestive cancers aim study report incidence prevalence survival across europe methods analysis carried 50 646 cases diagnosed 1995 2002 within population 162 000 000 21 european countries age standardised incidence rates computed using european standard population prevalence rates relative survival period survival indicators years 2000 2002 calculated expected number new cases per year prevalent cases europe estimated results large variations gallbladder epithelial cancer incidence rates incidence eastern europe 7 times higher uk ireland differences incidence rates smaller sites estimated number new epithelial cancers arising eu year estimated 11 050 extrahepatic bile duct cancer 10 713 gallbladder cancer 5427 anal cancer 3595 small intestine cancer corresponding estimated number total prevalent cases 18 483 15 620 40 589 13 276 also large variation 5 year relative survival rate epithelial cancer anal canal varied 66 central europe 44 eastern europe corresponding rates small intestine cancers 33 20 extrahepatic bile duct cancers 17 12 gallbladder cancer 13 10 conclusion large variations within europe incidence survival rare digestive cancers according geographic area pubmed","probabilities":0.9799733,"Title":"Incidence, prevalence and survival of patients with rare epithelial digestive cancers diagnosed in Europe in 1995-2002","Abstract":"BACKGROUND AND AIMS: Little is known about the epidemiology of rare epithelial digestive cancers. The aim of this study was to report on their incidence, prevalence and survival across Europe. METHODS: The analysis was carried out on 50,646 cases diagnosed from 1995 to 2002 within a population of 162,000,000 in 21 European countries. Age-standardised incidence rates were computed using the European standard population. Prevalence rates, relative survival and period survival indicators for the years 2000-2002 were calculated. The expected number of new cases per year and of prevalent cases in Europe was estimated. RESULTS: There were large variations in gallbladder epithelial cancer incidence rates: the incidence in Eastern Europe was 7 times higher than in the UK & Ireland. Differences between incidence rates were smaller for the other sites. The estimated number of new epithelial cancers arising in the EU each year was estimated to be 11,050 for extrahepatic bile duct cancer, 10,713 for gallbladder cancer, 5427 for anal cancer and 3595 for small intestine cancer. The corresponding estimated number of total prevalent cases was 18,483, 15,620, 40,589 and 13,276. There was also a large variation in the 5-year relative survival rate. For epithelial cancer of the anal canal, this varied between 66% (Central Europe) and 44% (Eastern Europe). The corresponding rates for small intestine cancers were 33% and 20%, for extrahepatic bile duct cancers, 17% and 12% and for gallbladder cancer 13% and 10%. CONCLUSION: There are large variations within Europe in the incidence and survival of rare digestive cancers according to geographic area.","Source":"PubMed","category":"HUMAN","training_data":"Incidence, prevalence and survival of patients with rare epithelial digestive cancers diagnosed in Europe in 1995-2002 BACKGROUND AND AIMS: Little is known about the epidemiology of rare epithelial digestive cancers. The aim of this study was to report on their incidence, prevalence and survival across Europe. METHODS: The analysis was carried out on 50,646 cases diagnosed from 1995 to 2002 within a population of 162,000,000 in 21 European countries. Age-standardised incidence rates were computed using the European standard population. Prevalence rates, relative survival and period survival indicators for the years 2000-2002 were calculated. The expected number of new cases per year and of prevalent cases in Europe was estimated. RESULTS: There were large variations in gallbladder epithelial cancer incidence rates: the incidence in Eastern Europe was 7 times higher than in the UK & Ireland. Differences between incidence rates were smaller for the other sites. The estimated number of new epithelial cancers arising in the EU each year was estimated to be 11,050 for extrahepatic bile duct cancer, 10,713 for gallbladder cancer, 5427 for anal cancer and 3595 for small intestine cancer. The corresponding estimated number of total prevalent cases was 18,483, 15,620, 40,589 and 13,276. There was also a large variation in the 5-year relative survival rate. For epithelial cancer of the anal canal, this varied between 66% (Central Europe) and 44% (Eastern Europe). The corresponding rates for small intestine cancers were 33% and 20%, for extrahepatic bile duct cancers, 17% and 12% and for gallbladder cancer 13% and 10%. CONCLUSION: There are large variations within Europe in the incidence and survival of rare digestive cancers according to geographic area. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression high mobility group hook 2 hmga2 intrahepatic cholangiocarcinomas independent prognostic marker associated poor prognosis background high mobility group hook 2 hmga2 important regulator cell growth differentiation apoptosis neoplastic transformation previous studies shown malignant tumors expressing hmga2 gastric lung colorectal carcinomas usually poor prognosis hmga2 expression clinical significance intrahepatic cholangiocarcinomas studied design identified 55 intrahepatic cholangiocarcinomas resected institute 1994 2003 h e slides cases reviewed histopathological features tumor size mitotic count tumor grade presence satellite nodules desmoplasia tumor necrosis vascular perineuronal invasion lymph node metastasis margin status recorded using immunohistochemical staining examined expression hmga2 p16 p53 kit afp ki 67 index associations clinicopathologic features immunohistochemical findings patient survival evaluated using cox proportional hazards regression results mean age 55 patients 21 male 34 female 60 9 years old twelve 23 cases positive lymph node metastasis expression hmga2 p16 p53 kit afp observed 18 32 26 47 37 69 21 38 2 4 intrahepatic cholangiocarcinomas respectively mean ki 67 index 9 1 ranging 0 90 univariate analysis showed hmga2 expression lymph node metastasis associated shorter patient survival p 0 02 0 03 respectively higher ki 67 index associated poor survival although reach statistical significance p 0 09 histopathological features expression status p16 p53 kit afp show associations patient survival multivariable analysis showed hmga 2 expression hazard ratio 2 10 p 0 03 lymph node metastasis hazard ratio 2 25 p 0 04 independent prognostic factors associated poor survival conclusions hmga2 expressed subset 32 intrahepatic cholangiocarcinomas independent prognostic marker associated poor survival google scholar","probabilities":0.54545456,"Title":"Expression Of High Mobility Group At-Hook 2 (Hmga2) In Intrahepatic Cholangiocarcinomas: An Independent Prognostic Marker Associated With Poor Prognosis","Abstract":"Background: High mobility group AT-hook 2 (HMGA2) is an important regulator for cell growth, differentiation, apoptosis, and neoplastic transformation. Previous studies have shown that malignant tumors expressing HMGA2 such as gastric, lung, and colorectal carcinomas usually had poor prognosis. HMGA2 expression and its clinical significance in intrahepatic cholangiocarcinomas have not been studied before. Design: We identified 55 intrahepatic cholangiocarcinomas resected at our institute from 1994 to 2003. H&E slides from all cases were reviewed and the histopathological features of tumor size, mitotic count, tumor grade, presence of satellite nodules, desmoplasia, tumor necrosis, vascular and perineuronal invasion, lymph node metastasis, and margin status were recorded. By using immunohistochemical staining, we examined expression of HMGA2, P16, P53, Kit, AFP, and Ki-67 index. Associations of clinicopathologic features and immunohistochemical findings with patient survival were evaluated using Cox proportional hazards regression. Results: The mean age of 55 patients (21 male; 34 female) was 60.9 years old. Twelve (23%) cases had positive lymph node metastasis. Expression of HMGA2, P16, P53, Kit, and AFP was observed in 18 (32%), 26 (47%), 37 (69%), 21 (38%), and 2 (4%) of the intrahepatic cholangiocarcinomas, respectively. The mean Ki-67 index was 9.1% (ranging from 0 – 90%). Univariate analysis showed that HMGA2 expression and lymph node metastasis were associated with shorter patient survival (p = 0.02 and 0.03, respectively). Higher Ki-67 index was associated poor survival although it did not reach statistical significance (p=0.09). The other histopathological features and the expression status of P16, P53, Kit, and AFP did not show associations with patient survival. Multivariable analysis showed that HMGA-2 expression (hazard ratio 2.10; p=0.03) and lymph node metastasis (hazard ratio 2.25; p=0.04) were independent prognostic factors associated with poor survival. Conclusions: HMGA2 is expressed in a subset (32%) of intrahepatic cholangiocarcinomas and is an independent prognostic marker associated with poor survival","Source":"Google Scholar","category":"HUMAN","training_data":"Expression Of High Mobility Group At-Hook 2 (Hmga2) In Intrahepatic Cholangiocarcinomas: An Independent Prognostic Marker Associated With Poor Prognosis Background: High mobility group AT-hook 2 (HMGA2) is an important regulator for cell growth, differentiation, apoptosis, and neoplastic transformation. Previous studies have shown that malignant tumors expressing HMGA2 such as gastric, lung, and colorectal carcinomas usually had poor prognosis. HMGA2 expression and its clinical significance in intrahepatic cholangiocarcinomas have not been studied before. Design: We identified 55 intrahepatic cholangiocarcinomas resected at our institute from 1994 to 2003. H&E slides from all cases were reviewed and the histopathological features of tumor size, mitotic count, tumor grade, presence of satellite nodules, desmoplasia, tumor necrosis, vascular and perineuronal invasion, lymph node metastasis, and margin status were recorded. By using immunohistochemical staining, we examined expression of HMGA2, P16, P53, Kit, AFP, and Ki-67 index. Associations of clinicopathologic features and immunohistochemical findings with patient survival were evaluated using Cox proportional hazards regression. Results: The mean age of 55 patients (21 male; 34 female) was 60.9 years old. Twelve (23%) cases had positive lymph node metastasis. Expression of HMGA2, P16, P53, Kit, and AFP was observed in 18 (32%), 26 (47%), 37 (69%), 21 (38%), and 2 (4%) of the intrahepatic cholangiocarcinomas, respectively. The mean Ki-67 index was 9.1% (ranging from 0 – 90%). Univariate analysis showed that HMGA2 expression and lymph node metastasis were associated with shorter patient survival (p = 0.02 and 0.03, respectively). Higher Ki-67 index was associated poor survival although it did not reach statistical significance (p=0.09). The other histopathological features and the expression status of P16, P53, Kit, and AFP did not show associations with patient survival. Multivariable analysis showed that HMGA-2 expression (hazard ratio 2.10; p=0.03) and lymph node metastasis (hazard ratio 2.25; p=0.04) were independent prognostic factors associated with poor survival. Conclusions: HMGA2 is expressed in a subset (32%) of intrahepatic cholangiocarcinomas and is an independent prognostic marker associated with poor survival Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"portal vein resection hilar cholangiocarcinoma hilar cholangiocarcinoma remains difficult challenge surgeon achieving negative surgical margins resecting relatively uncommon tumor technically demanding result close proximity bile duct bifurcation vascular inflow liver recent advance surgical treatment addition portal vein resection procedure resection portal vein increases number patients offered potentially curative approach technically difficult may increase risk procedure study reviews results portal vein resection hilar cholangiocarcinoma 1998 2005 60 patients underwent potentially curative resections hilar cholangiocarcinoma mean patient age 64 12 years range 24 85 years liver resections performed along biliary resection included 49 trisegmentectomies 37 right 12 left 10 lobectomies 8 left 2 right one patient bile duct resected four patients also simultaneous pancreaticoduodenectomy performed twenty six patients required portal vein resection reconstruction achieve negative margins 3 also required reconstruction hepatic artery operative mortality 8 per cent overall complication rate 40 per cent patients underwent portal vein resection operative mortality 4 per cent different 12 per cent mortality patients undergo portal vein resection p 0 39 differenceinactuarialpatientsurvivalbetweenpatientswhounderwentportalveinresectionand 5 year survival 39 per cent vs 41 per cent p significant negative margins achieved 80 per cent cases associated improved survival p 0 01 five yearactuarialsurvivalinpatientsundergoingresectionwithnegativemarginswas 45percent therewasnodifferenceinmarginstatusorlong termsurvivalbetweenthosepatients underwent portal vein resection negative margin status associated improved survival multivariate analysis portal vein resection hilar cholangiocarcinoma safe allows chance long term survival otherwise unresectable patients google scholar","probabilities":0.9799733,"Title":"Portal Vein Resection For Hilar Cholangiocarcinoma","Abstract":"Hilar cholangiocarcinoma remains a difficult challenge for the surgeon. Achieving negative surgical margins when resecting this relatively uncommon tumor is technically demanding as a result of the close proximity of the bile duct bifurcation to the vascular inflow of the liver. A recent advance in surgical treatment is the addition of portal vein resection to the procedure. Resection of the portal vein increases the number of patients offered a potentially curative approach but is technically more difficult and may increase the risk of the procedure. This study reviews the results of portal vein resection for hilar cholangiocarcinoma. Between 1998 and 2005, 60 patients underwent potentially curative resections of hilar cholangiocarcinoma. Mean patient age was 64 ± 12 years (range, 24–85 years). Liver resections performed along with biliary resection included 49 trisegmentectomies (37 right, 12 left) and 10 lobectomies (8 left, 2 right). One patient had only the bile duct resected. Four patients also had simultaneous pancreaticoduodenectomy performed. Twenty-six patients required portal vein resection and reconstruction to achieve negative margins, 3 of which also required reconstruction of the hepatic artery. Operative mortality was 8 per cent with an overall complication rate of 40 per cent. Patients who underwent portal vein resection had an operative mortality of 4 per cent, which was not different from the 12 per cent mortality in patients who did not undergo portal vein resection (P = 0.39). There was no differenceinactuarialpatientsurvivalbetweenpatientswhounderwentportalveinresectionand those who did not (5-year survival 39 per cent vs. 41 per cent, P = not significant). Negative margins were achieved in 80 per cent of cases and were associated with improved survival (P<0.01).Five-yearactuarialsurvivalinpatientsundergoingresectionwithnegativemarginswas 45percent.Therewasnodifferenceinmarginstatusorlong-termsurvivalbetweenthosepatients who underwent portal vein resection and those who did not. Only negative margin status was associated with improved survival by multivariate analysis. Portal vein resection for hilar cholangiocarcinoma is safe and allows a chance for long-term survival in otherwise unresectable patients.","Source":"Google Scholar","category":"HUMAN","training_data":"Portal Vein Resection For Hilar Cholangiocarcinoma Hilar cholangiocarcinoma remains a difficult challenge for the surgeon. Achieving negative surgical margins when resecting this relatively uncommon tumor is technically demanding as a result of the close proximity of the bile duct bifurcation to the vascular inflow of the liver. A recent advance in surgical treatment is the addition of portal vein resection to the procedure. Resection of the portal vein increases the number of patients offered a potentially curative approach but is technically more difficult and may increase the risk of the procedure. This study reviews the results of portal vein resection for hilar cholangiocarcinoma. Between 1998 and 2005, 60 patients underwent potentially curative resections of hilar cholangiocarcinoma. Mean patient age was 64 ± 12 years (range, 24–85 years). Liver resections performed along with biliary resection included 49 trisegmentectomies (37 right, 12 left) and 10 lobectomies (8 left, 2 right). One patient had only the bile duct resected. Four patients also had simultaneous pancreaticoduodenectomy performed. Twenty-six patients required portal vein resection and reconstruction to achieve negative margins, 3 of which also required reconstruction of the hepatic artery. Operative mortality was 8 per cent with an overall complication rate of 40 per cent. Patients who underwent portal vein resection had an operative mortality of 4 per cent, which was not different from the 12 per cent mortality in patients who did not undergo portal vein resection (P = 0.39). There was no differenceinactuarialpatientsurvivalbetweenpatientswhounderwentportalveinresectionand those who did not (5-year survival 39 per cent vs. 41 per cent, P = not significant). Negative margins were achieved in 80 per cent of cases and were associated with improved survival (P<0.01).Five-yearactuarialsurvivalinpatientsundergoingresectionwithnegativemarginswas 45percent.Therewasnodifferenceinmarginstatusorlong-termsurvivalbetweenthosepatients who underwent portal vein resection and those who did not. Only negative margin status was associated with improved survival by multivariate analysis. Portal vein resection for hilar cholangiocarcinoma is safe and allows a chance for long-term survival in otherwise unresectable patients. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"incidence non lung solid cancers czech uranium miners case cohort study objectives uranium miners chronically exposed radon progeny known cause lung cancer may associated leukemia study undertaken evaluate risk non lung solid cancers among uranium miners p bram region czech republic methods retrospective stratified case cohort study cohort 22 816 underground miners employed 1949 1975 incident non lung solid cancers ascertained among miners worked underground least 12 months n 1020 subcohort 1707 subjects randomly drawn population random sampling stratified age follow period lasted 1977 1996 results relative risks comparing 180 wlm 90th percentile cumulative lifetime radon exposure 3 wlm 10th percentile 0 88 non lung solid cancers combined 95 ci 0 73 1 04 n 1020 0 87 digestive cancers 95 ci 0 69 1 09 n 561 2 39 gallbladder cancer 95 ci 0 52 10 98 n 13 0 79 larynx cancer 95 ci 0 38 1 64 n 62 2 92 malignant melanoma 95 ci 0 91 9 42 n 23 0 84 bladder cancer 95 ci 0 43 1 65 n 73 1 13 kidney cancer 95 ci 0 62 2 04 n 66 cancer type significantly associated radon exposure malignant melanoma gallbladder cancer showed elevated non significant association radon conclusions radon significantly associated incidence cancer interest although positive association radon malignant melanoma gallbladder cancer entirely ruled pubmed","probabilities":0.9799733,"Title":"Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study","Abstract":"OBJECTIVES: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic. METHODS: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. RESULTS: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. CONCLUSIONS: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out.","Source":"PubMed","category":"HUMAN","training_data":"Incidence of non-lung solid cancers in Czech uranium miners: a case-cohort study OBJECTIVES: Uranium miners are chronically exposed to radon and its progeny, which are known to cause lung cancer and may be associated with leukemia. This study was undertaken to evaluate risk of non-lung solid cancers among uranium miners in Příbram region, Czech Republic. METHODS: A retrospective stratified case-cohort study in a cohort of 22,816 underground miners who were employed between 1949 and 1975. All incident non-lung solid cancers were ascertained among miners who worked underground for at least 12 months (n=1020). A subcohort of 1707 subjects was randomly drawn from the same population by random sampling stratified on age. The follow-up period lasted from 1977 to 1996. RESULTS: Relative risks comparing 180 WLM (90th percentile) of cumulative lifetime radon exposure to 3 WLM (10th percentile) were 0.88 for all non-lung solid cancers combined (95% CI 0.73-1.04, n=1020), 0.87 for all digestive cancers (95% CI 0.69-1.09, n=561), 2.39 for gallbladder cancer (95% CI 0.52-10.98, n=13), 0.79 for larynx cancer (95% CI 0.38-1.64, n=62), 2.92 for malignant melanoma (95% CI 0.91-9.42, n=23), 0.84 for bladder cancer (95% CI 0.43-1.65, n=73), and 1.13 for kidney cancer (95% CI 0.62-2.04, n=66). No cancer type was significantly associated with radon exposure; only malignant melanoma and gallbladder cancer showed elevated but non-significant association with radon. CONCLUSIONS: Radon was not significantly associated with incidence of any cancer of interest, although a positive association of radon with malignant melanoma and gallbladder cancer cannot be entirely ruled out. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tobacco alcohol use risk hepatocellular carcinoma intrahepatic cholangiocarcinoma liver cancer pooling project background tobacco alcohol established risk factors hepatocellular carcinoma hcc common type primary liver cancer unknown whether also increase risk intrahepatic cholangiocarcinoma icc thus examined association tobacco alcohol use primary liver cancer type methods liver cancer pooling project consortium 14 us based prospective cohort studies includes data 1 518 741 individuals hcc n 1423 icc n 410 multivariable adjusted hazards ratios hrs 95 confidence intervals ci estimated using proportional hazards regression results current smokers baseline increased risk hcc hazard ratio hr 1 86 95 confidence interval ci 1 57 2 20 icc hr 1 47 95 ci 1 07 2 02 among individuals quit smoking 30 years ago hcc risk almost equivalent never smokers hr 1 09 95 ci 0 74 1 61 compared non drinkers heavy alcohol consumption associated 87 increased hcc risk hr 7 drinks day 1 87 95 ci 1 41 2 47 68 increased icc risk hr 5 drinks day 1 68 95 ci 0 99 2 86 however light moderate alcohol consumption 3 drinks day appeared inversely associated hcc risk hr 0 0 5 drinks day 0 77 95 ci 0 67 0 89 hr 0 5 1 drinks day 0 57 95 ci 0 44 0 73 hr 1 3 drinks day 0 71 95 ci 0 58 0 87 icc conclusions findings suggest relatively healthy population smoking cessation light moderate drinking may reduce risk hcc pubmed","probabilities":0.9799733,"Title":"Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project","Abstract":"BACKGROUND: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type. METHODS: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. RESULTS: Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR(≥7 drinks/day) = 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR(≥5 drinks/day) = 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR(>0-<0.5 drinks/day) = 0.77, 95% CI: 0.67-0.89; HR(>0.5-<1 drinks/day) = 0.57, 95% CI: 0.44-0.73; HR(1-<3 drinks/day) = 0.71, 95% CI: 0.58-0.87), but not ICC. CONCLUSIONS: These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC.","Source":"PubMed","category":"HUMAN","training_data":"Tobacco, alcohol use and risk of hepatocellular carcinoma and intrahepatic cholangiocarcinoma: The Liver Cancer Pooling Project BACKGROUND: While tobacco and alcohol are established risk factors for hepatocellular carcinoma (HCC), the most common type of primary liver cancer, it is unknown whether they also increase the risk of intrahepatic cholangiocarcinoma (ICC). Thus, we examined the association between tobacco and alcohol use by primary liver cancer type. METHODS: The Liver Cancer Pooling Project is a consortium of 14 US-based prospective cohort studies that includes data from 1,518,741 individuals (HCC n = 1423, ICC n = 410). Multivariable-adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were estimated using proportional hazards regression. RESULTS: Current smokers at baseline had an increased risk of HCC (hazard ratio (HR) = 1.86, 95% confidence interval (CI): 1.57-2.20) and ICC (HR = 1.47, 95% CI: 1.07-2.02). Among individuals who quit smoking >30 years ago, HCC risk was almost equivalent to never smokers (HR = 1.09, 95% CI: 0.74-1.61). Compared to non-drinkers, heavy alcohol consumption was associated with an 87% increased HCC risk (HR(≥7 drinks/day) = 1.87, 95% CI: 1.41-2.47) and a 68% increased ICC risk (HR(≥5 drinks/day) = 1.68, 95% CI: 0.99-2.86). However, light-to-moderate alcohol consumption of <3 drinks/day appeared to be inversely associated with HCC risk (HR(>0-<0.5 drinks/day) = 0.77, 95% CI: 0.67-0.89; HR(>0.5-<1 drinks/day) = 0.57, 95% CI: 0.44-0.73; HR(1-<3 drinks/day) = 0.71, 95% CI: 0.58-0.87), but not ICC. CONCLUSIONS: These findings suggest that, in this relatively healthy population, smoking cessation and light-to-moderate drinking may reduce the risk of HCC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemic trends obesity impact metabolism digestive diseases currently 14 world population pre obese obese percentage even higher developed countries obesity important risk factor vast number nonmalignant malignant digestive diseases important examples cholelithiasis nonalcoholic fatty liver disease gastroesophageal reflux disease one hand esophageal adenocarcinoma gastric cardia adenocarcinoma pancreatic cancer liver cancer gallbladder cancer colorectal cancer hand epidemic trends reported recent studies reviewed knowledge dependencies obesity yield deeper understanding necessary improve prevention treatment concepts epidemic pubmed","probabilities":0.9799733,"Title":"Epidemic trends of obesity with impact on metabolism and digestive diseases","Abstract":"Currently, more than 14% of the world's population is pre-obese or obese. The percentage is even higher in developed countries. Obesity is an important risk factor for a vast number of nonmalignant and malignant digestive diseases. Some of the more important examples are cholelithiasis, nonalcoholic fatty liver disease, and gastroesophageal reflux disease on the one hand and esophageal adenocarcinoma, gastric cardia adenocarcinoma, pancreatic cancer, liver cancer, gallbladder cancer, and colorectal cancer on the other hand. Their epidemic trends as reported in recent studies are reviewed here. Knowledge of their dependencies on obesity will yield a deeper understanding which is necessary to improve prevention and treatment concepts of this epidemic.","Source":"PubMed","category":"HUMAN","training_data":"Epidemic trends of obesity with impact on metabolism and digestive diseases Currently, more than 14% of the world's population is pre-obese or obese. The percentage is even higher in developed countries. Obesity is an important risk factor for a vast number of nonmalignant and malignant digestive diseases. Some of the more important examples are cholelithiasis, nonalcoholic fatty liver disease, and gastroesophageal reflux disease on the one hand and esophageal adenocarcinoma, gastric cardia adenocarcinoma, pancreatic cancer, liver cancer, gallbladder cancer, and colorectal cancer on the other hand. Their epidemic trends as reported in recent studies are reviewed here. Knowledge of their dependencies on obesity will yield a deeper understanding which is necessary to improve prevention and treatment concepts of this epidemic. PubMed","prediction_labels":"HUMAN"},{"cleaned":"nitinol biliary stent versus surgery palliation distal malignant biliary obstruction background curative resection pancreatic biliary malignancies rare tumors inoperable presentation palliation jaundice often goal biliary decompression achieved surgical diversion endoscopic biliary stents study aimed compare clinical outcomes surgical bypass endoscopic uncovered nitinol stents palliation patients malignant distal common bile duct obstruction methods multicenter retrospective cohort study investigated 86 patients inoperable malignant distal common bile duct strictures tertiary referral centers medell n colombia patients undergone surgery group 1 placement uncovered 30 fr self expandable nitinol stent produced locally medell n colombia group 2 main outcome measurements included cumulative biliary patency hospital stay patient survival results study enrolled 86 patients mean age 66 years range 43 78 years including 40 patients group 1 46 patients group 2 groups similar terms age gender liver metastasis diagnosis technical success achieved 38 patients group 1 95 43 patients group 2 93 functional biliary decompression obtained 35 surgical patients 88 42 stented patients 91 group 2 lower rates procedure related mortality 2 vs 7 5 p 0 01 lower frequency early complications 8 7 vs 45 p 0 02 shorter hospital stay median 6 vs 12 days p 0 01 recurrent jaundice occurred three patients group 1 7 5 eight patients group 2 17 3 p 0 198 late gastric outlet obstruction occurred 12 5 patients group 1 13 patients group 2 p 0 73 despite early benefits stenting significant difference median overall survival two groups found group 1 163 days group 2 178 days p 0 11 limitations study included small number patients retrospective design conclusions endoscopic stenting surgery effective palliation former associated fewer early complications latter fewer late complications patients qualify curative resection may better managed stent placement surgery reserved patients likely survive longer pubmed","probabilities":0.9799733,"Title":"Nitinol biliary stent versus surgery for palliation of distal malignant biliary obstruction","Abstract":"BACKGROUND: Curative resection of pancreatic and biliary malignancies is rare. Most tumors are inoperable at presentation, and palliation of jaundice often is the goal. Biliary decompression can be achieved by surgical diversion or endoscopic biliary stents. This study aimed to compare clinical outcomes between surgical bypass and endoscopic uncovered nitinol stents in the palliation of patients with malignant distal common bile duct obstruction. METHODS: A multicenter, retrospective, cohort study investigated 86 patients with inoperable malignant distal common bile duct strictures at tertiary referral centers in Medellín, Colombia. These patients had undergone surgery (group 1) or placement of an uncovered 30-Fr self-expandable nitinol stent produced locally in Medellín, Colombia (group 2). The main outcome measurements included cumulative biliary patency, hospital stay, and patient survival. RESULTS: The study enrolled 86 patients (mean age, 66 years; range, 43-78 years) including 40 patients in group 1 and 46 patients in group 2. Both groups were similar in terms of age, gender, liver metastasis, and diagnosis. Technical success was achieved for 38 patients in group 1 (95%) and 43 patients in group 2 (93%). Functional biliary decompression was obtained in for 35 of the surgical patients (88%) and 42 of the stented patients (91%). Group 2 had lower rates for procedure-related mortality (2 vs. 7.5%; p = 0.01), a lower frequency of early complications (8.7 vs. 45%; p = 0.02), and a shorter hospital stay (median, 6 vs. 12 days; p = 0.01). Recurrent jaundice occurred for three patients in group 1 (7.5%) and eight patients in group 2 (17.3%) (p = 0.198). Late gastric outlet obstruction occurred for 12.5% of the patients in group 1 and 13% of the patients in group 2 (p = 0.73). Despite the early benefits of stenting, no significant difference in the median overall survival between the two groups was found (group 1, 163 days; group 2, 178 days; p = 0.11). The limitations of this study included the small number of patients and the retrospective design. CONCLUSIONS: Endoscopic stenting and surgery are effective palliation. The former is associated with fewer early complications and the latter with fewer late complications. Patients who do not qualify for curative resection may be better managed by stent placement. Surgery should be reserved for patients more likely to survive longer.","Source":"PubMed","category":"HUMAN","training_data":"Nitinol biliary stent versus surgery for palliation of distal malignant biliary obstruction BACKGROUND: Curative resection of pancreatic and biliary malignancies is rare. Most tumors are inoperable at presentation, and palliation of jaundice often is the goal. Biliary decompression can be achieved by surgical diversion or endoscopic biliary stents. This study aimed to compare clinical outcomes between surgical bypass and endoscopic uncovered nitinol stents in the palliation of patients with malignant distal common bile duct obstruction. METHODS: A multicenter, retrospective, cohort study investigated 86 patients with inoperable malignant distal common bile duct strictures at tertiary referral centers in Medellín, Colombia. These patients had undergone surgery (group 1) or placement of an uncovered 30-Fr self-expandable nitinol stent produced locally in Medellín, Colombia (group 2). The main outcome measurements included cumulative biliary patency, hospital stay, and patient survival. RESULTS: The study enrolled 86 patients (mean age, 66 years; range, 43-78 years) including 40 patients in group 1 and 46 patients in group 2. Both groups were similar in terms of age, gender, liver metastasis, and diagnosis. Technical success was achieved for 38 patients in group 1 (95%) and 43 patients in group 2 (93%). Functional biliary decompression was obtained in for 35 of the surgical patients (88%) and 42 of the stented patients (91%). Group 2 had lower rates for procedure-related mortality (2 vs. 7.5%; p = 0.01), a lower frequency of early complications (8.7 vs. 45%; p = 0.02), and a shorter hospital stay (median, 6 vs. 12 days; p = 0.01). Recurrent jaundice occurred for three patients in group 1 (7.5%) and eight patients in group 2 (17.3%) (p = 0.198). Late gastric outlet obstruction occurred for 12.5% of the patients in group 1 and 13% of the patients in group 2 (p = 0.73). Despite the early benefits of stenting, no significant difference in the median overall survival between the two groups was found (group 1, 163 days; group 2, 178 days; p = 0.11). The limitations of this study included the small number of patients and the retrospective design. CONCLUSIONS: Endoscopic stenting and surgery are effective palliation. The former is associated with fewer early complications and the latter with fewer late complications. Patients who do not qualify for curative resection may be better managed by stent placement. Surgery should be reserved for patients more likely to survive longer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"adjuvant chemoradiotherapy curative resection extrahepatic bile duct cancer long term single center experience objectives analyze outcome adjuvant chemoradiotherapy patients extrahepatic bile duct ehbd cancer identify prognostic factors patients methods january 1995 december 2002 86 patients adenocarcinoma ehbd underwent curative resection followed adjuvant chemoradiotherapy 59 male 27 female patients median age 59 years range 34 73 y postoperative radiotherapy delivered tumor bed regional lymph nodes 40 gy 2 gy fraction 2 week planned rest intravenous 5 fluorouracil 500 mg m 2 d given day 1 3 split course median follow period 83 months survivors results forty eight patients failed treatment locoregional recurrence 20 distant metastasis 38 locoregional distant relapses 10 patients five year locoregional relapse free survival rate 70 3 multivariate analysis resection margin status significant prognosticator p 0 0299 five year distant metastasis free survival rate 53 6 three involved lymph nodes adverse impact distant metastasis free survival p 0 0334 five year overall survival rate 44 7 poorly differentiated tumor associated inferior overall survival p 0 0297 conclusions adjuvant chemoradiotherapy curative resection achieve long term survival patients ehbd cancer resection margin status number involved lymph nodes histologic differentiation associated locoregional relapse distant metastasis overall survival respectively distant metastasis major pattern failure possibly due increased locoregional control use adjuvant chemoradiotherapy intensification systemic treatment warranted pubmed","probabilities":0.9799733,"Title":"Adjuvant chemoradiotherapy after curative resection for extrahepatic bile duct cancer: a long-term single center experience","Abstract":"OBJECTIVES: To analyze the outcome of adjuvant chemoradiotherapy for patients with extrahepatic bile duct (EHBD) cancer, and to identify the prognostic factors for these patients. METHODS: Between January 1995 and December 2002, 86 patients with adenocarcinoma of EHBD underwent curative resection followed by adjuvant chemoradiotherapy. There were 59 male and 27 female patients, and median age was 59 years (range, 34 to 73 y). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40 Gy at 2 Gy/fraction with a 2-week planned rest. Intravenous 5-fluorouracil (500 mg/m(2)/d) was given on day 1 to 3 of each split course. The median follow-up period was 83 months for survivors. RESULTS: Forty-eight patients failed the treatment: locoregional recurrence in 20, distant metastasis in 38, and both locoregional and distant relapses in 10 patients. Five-year locoregional relapse-free survival rate was 70.3%. On multivariate analysis, resection margin status was the only significant prognosticator (P=0.0299). Five-year distant metastasis-free survival rate was 53.6%. Three or more involved lymph nodes had an adverse impact on distant metastasis-free survival (P=0.0334). Five-year overall survival rate was 44.7%, and poorly differentiated tumor was associated with inferior overall survival (P=0.0297). CONCLUSIONS: Adjuvant chemoradiotherapy after curative resection can achieve a long-term survival in patients with EHBD cancer. Resection margin status, number of involved lymph nodes, and histologic differentiation are associated with locoregional relapse, distant metastasis, and overall survival, respectively. Distant metastasis was the major pattern of failure, possibly due to the increased locoregional control by use of adjuvant chemoradiotherapy. Intensification of systemic treatment is warranted.","Source":"PubMed","category":"HUMAN","training_data":"Adjuvant chemoradiotherapy after curative resection for extrahepatic bile duct cancer: a long-term single center experience OBJECTIVES: To analyze the outcome of adjuvant chemoradiotherapy for patients with extrahepatic bile duct (EHBD) cancer, and to identify the prognostic factors for these patients. METHODS: Between January 1995 and December 2002, 86 patients with adenocarcinoma of EHBD underwent curative resection followed by adjuvant chemoradiotherapy. There were 59 male and 27 female patients, and median age was 59 years (range, 34 to 73 y). Postoperative radiotherapy was delivered to tumor bed and regional lymph nodes up to 40 Gy at 2 Gy/fraction with a 2-week planned rest. Intravenous 5-fluorouracil (500 mg/m(2)/d) was given on day 1 to 3 of each split course. The median follow-up period was 83 months for survivors. RESULTS: Forty-eight patients failed the treatment: locoregional recurrence in 20, distant metastasis in 38, and both locoregional and distant relapses in 10 patients. Five-year locoregional relapse-free survival rate was 70.3%. On multivariate analysis, resection margin status was the only significant prognosticator (P=0.0299). Five-year distant metastasis-free survival rate was 53.6%. Three or more involved lymph nodes had an adverse impact on distant metastasis-free survival (P=0.0334). Five-year overall survival rate was 44.7%, and poorly differentiated tumor was associated with inferior overall survival (P=0.0297). CONCLUSIONS: Adjuvant chemoradiotherapy after curative resection can achieve a long-term survival in patients with EHBD cancer. Resection margin status, number of involved lymph nodes, and histologic differentiation are associated with locoregional relapse, distant metastasis, and overall survival, respectively. Distant metastasis was the major pattern of failure, possibly due to the increased locoregional control by use of adjuvant chemoradiotherapy. Intensification of systemic treatment is warranted. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatolithiasis intrahepatic cholangiocarcinoma review although incidence hepatolithiasis decreasing pattern gallstone disease changes asia prevalence hepatolithiasis persistently high especially far eastern countries hepatolithiasis established risk factor cholangiocarcinoma cca chronic proliferative inflammation may involved biliary carcinogenesis inducing upregulation cell proliferating factors use advanced imaging modalities much improvement management hepatolithiasis diagnosis hepatolithiasis associated cca hl cca however many problems managing strictures hepatolithiasis differentiating infiltrating types cca surgical resection recommended cases single lobe hepatolithiasis atrophy uncontrolled stricture symptom duration 10 years long history biliary enteric anastomosis even resection patients followed caution development hl cca hl cca independent prognostic factor survival yet clear whether hepatic resection reduce occurrence subsequent hl cca furthermore consistent findings regarding prediction subsequent hl cca patients hepatolithiasis management hepatolithiasis important factors reduction recurrence cholangitis suspicion unrecognized hl cca pubmed","probabilities":0.962963,"Title":"Hepatolithiasis and intrahepatic cholangiocarcinoma: A review","Abstract":"Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma (CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA (HL-CCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliary-enteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA.","Source":"PubMed","category":"HUMAN","training_data":"Hepatolithiasis and intrahepatic cholangiocarcinoma: A review Although the incidence of hepatolithiasis is decreasing as the pattern of gallstone disease changes in Asia, the prevalence of hepatolithiasis is persistently high, especially in Far Eastern countries. Hepatolithiasis is an established risk factor for cholangiocarcinoma (CCA), and chronic proliferative inflammation may be involved in biliary carcinogenesis and in inducing the upregulation of cell-proliferating factors. With the use of advanced imaging modalities, there has been much improvement in the management of hepatolithiasis and the diagnosis of hepatolithiasis-associated CCA (HL-CCA). However, there are many problems in managing the strictures in hepatolithiasis and differentiating them from infiltrating types of CCA. Surgical resection is recommended in cases of single lobe hepatolithiasis with atrophy, uncontrolled stricture, symptom duration of more than 10 years, and long history of biliary-enteric anastomosis. Even after resection, patients should be followed with caution for development of HL-CCA, because HL-CCA is an independent prognostic factor for survival. It is not yet clear whether hepatic resection can reduce the occurrence of subsequent HL-CCA. Furthermore, there are no consistent findings regarding prediction of subsequent HL-CCA in patients with hepatolithiasis. In the management of hepatolithiasis, important factors are the reduction of recurrence of cholangitis and suspicion of unrecognized HL-CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pancreaticobiliary maljunction associated common bile duct carcinoma meta analysis objective pancreaticobiliary maljunction pbm reported associated increased risk gallbladder carcinoma however relationship pbm common bile duct carcinoma cbdc remains unclear aimed conduct meta analysis determine available evidence association pbm cbdc methods pooled odds ratio standard mean differences smd 95 confidence interval 95 ci used estimate effects results total eight case control studies two cohort studies identified incidence pbm higher cbdc patients controls 1 45 95 ci 1 19 1 76 compared patients without pbm cbdc patients pbm younger diagnosis age smd 0 46 95 ci 0 64 0 28 difference incidence associated cdc found cbdc patients without pbm 2 14 95 ci 1 60 2 87 conclusions compared benign biliary tract diseases incidence pbm higher cbdc patients especially relatively young patients also found incidence cdc higher cbdc patients pbm findings showed positive association pbm cbdc may help identifying high risk individuals pubmed","probabilities":0.9799733,"Title":"Pancreaticobiliary maljunction is associated with common bile duct carcinoma: a meta-analysis","Abstract":"OBJECTIVE: Pancreaticobiliary maljunction (PBM) has been reported to be associated with an increased risk of gallbladder carcinoma. However, the relationship between PBM and common bile duct carcinoma (CBDC) remains unclear. We aimed to conduct a meta-analysis to determine the available evidence on the association between PBM and CBDC. METHODS: The pooled odds ratio (OR) and standard mean differences (SMD) with 95% confidence interval (95% CI) were used to estimate the effects. RESULTS: A total of eight case-control studies and two cohort studies were identified. The incidence of PBM was higher in CBDC patients than in controls (OR = 1.45; 95% CI, 1.19-1.76). Compared with patients without PBM, CBDC patients with PBM were younger at the diagnosis age (SMD = -0.46; 95% CI, -0.64 to -0.28). A difference in the incidence of associated CDC was found between CBDC patients with or without PBM (OR = 2.14; 95% CI, 1.60-2.87). CONCLUSIONS: Compared with benign biliary tract diseases, the incidence of PBM was higher in CBDC patients, especially in relatively young patients. We also found that the incidence of CDC was higher in CBDC patients with PBM. These findings showed positive association between PBM and CBDC, which may help in identifying high-risk individuals.","Source":"PubMed","category":"HUMAN","training_data":"Pancreaticobiliary maljunction is associated with common bile duct carcinoma: a meta-analysis OBJECTIVE: Pancreaticobiliary maljunction (PBM) has been reported to be associated with an increased risk of gallbladder carcinoma. However, the relationship between PBM and common bile duct carcinoma (CBDC) remains unclear. We aimed to conduct a meta-analysis to determine the available evidence on the association between PBM and CBDC. METHODS: The pooled odds ratio (OR) and standard mean differences (SMD) with 95% confidence interval (95% CI) were used to estimate the effects. RESULTS: A total of eight case-control studies and two cohort studies were identified. The incidence of PBM was higher in CBDC patients than in controls (OR = 1.45; 95% CI, 1.19-1.76). Compared with patients without PBM, CBDC patients with PBM were younger at the diagnosis age (SMD = -0.46; 95% CI, -0.64 to -0.28). A difference in the incidence of associated CDC was found between CBDC patients with or without PBM (OR = 2.14; 95% CI, 1.60-2.87). CONCLUSIONS: Compared with benign biliary tract diseases, the incidence of PBM was higher in CBDC patients, especially in relatively young patients. We also found that the incidence of CDC was higher in CBDC patients with PBM. These findings showed positive association between PBM and CBDC, which may help in identifying high-risk individuals. PubMed","prediction_labels":"HUMAN"},{"cleaned":"overweight obesity risk gallbladder extrahepatic bile duct cancers meta analysis observational studies objective epidemiological studies repeatedly investigated association excess body weight risk biliary tract cancer inconsistent results objective study quantitatively assess associations overweight obesity risk biliary tract cancer methods comprehensive search pubmed embase web science china national knowledge infrastructure databases august 2015 conducted reference lists retrieved articles additional relevant studies manually searched results fourteen prospective cohort studies 15 case control studies included meta analysis studies included 11 448 397 participants 6 733 patients gallbladder cancer gbc 5 798 patients extrahepatic bile duct cancer ebdc follow durations ranging 5 23 years among overweight adults pooled rr 1 17 95 ci 1 07 1 28 gbc 1 26 95 ci 1 14 1 39 ebdc among people obesity pooled rr 1 62 95 ci 1 49 1 75 gbc 1 48 95 ci 1 21 1 81 ebdc visual inspection funnel plots begg egger tests show enough evidence publication bias conclusions integrated evidence meta analysis suggests excess body weight associated significantly increased risk gbc ebdc pubmed","probabilities":0.9799733,"Title":"Overweight, obesity and the risk of gallbladder and extrahepatic bile duct cancers: A meta-analysis of observational studies","Abstract":"OBJECTIVE: Epidemiological studies have repeatedly investigated the association between excess body weight and the risk of biliary tract cancer with inconsistent results. The objective of this study was to quantitatively assess the associations between overweight and obesity and the risk of biliary tract cancer. METHODS: A comprehensive search of PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to August 2015 was conducted, and the reference lists of retrieved articles for additional relevant studies were manually searched. RESULTS: Fourteen prospective cohort studies and 15 case-control studies were included in this meta-analysis. These studies included 11,448,397 participants (6,733 patients with gallbladder cancer [GBC] and 5,798 patients with extrahepatic bile duct cancer [EBDC]) with follow-up durations ranging from 5 to 23 years. Among overweight adults, the pooled RR was 1.17 (95% CI, 1.07-1.28) for GBC and 1.26 (95% CI, 1.14-1.39) for EBDC, and among people with obesity, the pooled RR was 1.62 (95% CI, 1.49-1.75) for GBC and 1.48 (95% CI, 1.21-1.81) for EBDC. Visual inspection of the funnel plots and the Begg's and the Egger's tests did not show enough evidence of publication bias. CONCLUSIONS: Integrated evidence from this meta-analysis suggests that excess body weight is associated with a significantly increased risk of GBC and EBDC.","Source":"PubMed","category":"HUMAN","training_data":"Overweight, obesity and the risk of gallbladder and extrahepatic bile duct cancers: A meta-analysis of observational studies OBJECTIVE: Epidemiological studies have repeatedly investigated the association between excess body weight and the risk of biliary tract cancer with inconsistent results. The objective of this study was to quantitatively assess the associations between overweight and obesity and the risk of biliary tract cancer. METHODS: A comprehensive search of PubMed, Embase, Web of Science, and China National Knowledge Infrastructure databases up to August 2015 was conducted, and the reference lists of retrieved articles for additional relevant studies were manually searched. RESULTS: Fourteen prospective cohort studies and 15 case-control studies were included in this meta-analysis. These studies included 11,448,397 participants (6,733 patients with gallbladder cancer [GBC] and 5,798 patients with extrahepatic bile duct cancer [EBDC]) with follow-up durations ranging from 5 to 23 years. Among overweight adults, the pooled RR was 1.17 (95% CI, 1.07-1.28) for GBC and 1.26 (95% CI, 1.14-1.39) for EBDC, and among people with obesity, the pooled RR was 1.62 (95% CI, 1.49-1.75) for GBC and 1.48 (95% CI, 1.21-1.81) for EBDC. Visual inspection of the funnel plots and the Begg's and the Egger's tests did not show enough evidence of publication bias. CONCLUSIONS: Integrated evidence from this meta-analysis suggests that excess body weight is associated with a significantly increased risk of GBC and EBDC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical pathological significance ros1 expression intrahepatic cholangiocarcinoma background knowledge genetic molecular features cholangiocarcinoma needed develop effective therapeutic strategies investigated clinical pathological significance ros1 expression intrahepatic cholangiocarcinoma methods one hundred ninety four patients curatively resected intrahepatic cholangiocarcinoma included study tumor tissue specimens collected analyzed ros1 gene rearrangement using fluorescence situ hybridization fish ros1 protein expression using immunohistochemistry ihc results ros1 immunohistochemistry positive moderate strong staining 72 tumors 37 1 ros1 protein expression significantly correlated well differentiated tumors papillary mucinous histology oncocytic hepatoid intestinal type tumors periductal infiltrating intraductal growing tumors vs mass forming cholangiocarcinoma ros expressing tumors associated better disease free survival 30 1 months ros1 expression tumors vs 9 0 months ros1 tumors p 0 006 moreover ros1 expression independent predictor better disease free survival multivariate analysis hr 0 607 95 ci 0 377 0 976 p 0 039 although break apart fish successfully performed 102 samples split pattern indicative ros1 gene rearrangement found examined samples conclusion ros1 protein expression associated well differentiated histology better survival patients resected intrahepatic cholangiocarcinoma ros1 gene rearrangement break apart fish found examined samples stn","probabilities":0.7966102,"Title":"Clinical And Pathological Significance Of Ros1 Expression In Intrahepatic Cholangiocarcinoma","Abstract":"Background: More knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies. We investigated the clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma. \n\n Methods: One hundred ninety-four patients with curatively resected intrahepatic cholangiocarcinoma were included in this study. Tumor tissue specimens were collected and analyzed for ROS1 gene rearrangement using fluorescence in situ hybridization (FISH) and ROS1 protein expression using immunohistochemistry (IHC). \n\n Results: ROS1 immunohistochemistry was positive (moderate or strong staining) in 72 tumors (37.1 %). ROS1 protein expression was significantly correlated with well differentiated tumors, papillary or mucinous histology, oncocytic/hepatoid or intestinal type tumors, and periductal infiltrating or intraductal growing tumors (vs. mass-forming cholangiocarcinoma). ROS-expressing tumors were associated with better disease-free survival (30.1 months for ROS1 expression (+) tumors vs. 9.0 months for ROS1 (-) tumors, p = 0.006). Moreover, ROS1 expression was an independent predictor of better disease-free survival in a multivariate analysis (HR 0.607, 95 % CI 0.377-0.976; p = 0.039). Although break-apart FISH was successfully performed in 102 samples, a split pattern indicative of ROS1 gene rearrangement was not found in the examined samples. \n\n Conclusion: ROS1 protein expression was associated with well-differentiated histology and better survival in our patients with resected intrahepatic cholangiocarcinoma. ROS1 gene rearrangement by break-apart FISH was not found in the examined samples.","Source":"STN","category":"HUMAN","training_data":"Clinical And Pathological Significance Of Ros1 Expression In Intrahepatic Cholangiocarcinoma Background: More knowledge about genetic and molecular features of cholangiocarcinoma is needed to develop effective therapeutic strategies. We investigated the clinical and pathological significance of ROS1 expression in intrahepatic cholangiocarcinoma. \n\n Methods: One hundred ninety-four patients with curatively resected intrahepatic cholangiocarcinoma were included in this study. Tumor tissue specimens were collected and analyzed for ROS1 gene rearrangement using fluorescence in situ hybridization (FISH) and ROS1 protein expression using immunohistochemistry (IHC). \n\n Results: ROS1 immunohistochemistry was positive (moderate or strong staining) in 72 tumors (37.1 %). ROS1 protein expression was significantly correlated with well differentiated tumors, papillary or mucinous histology, oncocytic/hepatoid or intestinal type tumors, and periductal infiltrating or intraductal growing tumors (vs. mass-forming cholangiocarcinoma). ROS-expressing tumors were associated with better disease-free survival (30.1 months for ROS1 expression (+) tumors vs. 9.0 months for ROS1 (-) tumors, p = 0.006). Moreover, ROS1 expression was an independent predictor of better disease-free survival in a multivariate analysis (HR 0.607, 95 % CI 0.377-0.976; p = 0.039). Although break-apart FISH was successfully performed in 102 samples, a split pattern indicative of ROS1 gene rearrangement was not found in the examined samples. \n\n Conclusion: ROS1 protein expression was associated with well-differentiated histology and better survival in our patients with resected intrahepatic cholangiocarcinoma. ROS1 gene rearrangement by break-apart FISH was not found in the examined samples. STN","prediction_labels":"HUMAN"},{"cleaned":"decreased sulfite oxidase expression strongly predicts survival patients resectable intrahepatic cholangiocarcinoma getting copy pasted properly go link google scholar","probabilities":0.9799733,"Title":"Decreased Sulfite Oxidase Expression Strongly Predicts Survival In Patients With Resectable Intrahepatic Cholangiocarcinoma","Abstract":"Not getting copy pasted properly. Go through the link","Source":"Google Scholar","category":"HUMAN","training_data":"Decreased Sulfite Oxidase Expression Strongly Predicts Survival In Patients With Resectable Intrahepatic Cholangiocarcinoma Not getting copy pasted properly. Go through the link Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"evolution surgical treatment perihilar cholangiocarcinoma single center 34 year review 574 consecutive resections objective review 34 year experience 574 consecutive resections perihilar cholangiocarcinoma evaluate progress made surgical treatment disease background studies reported improved surgical outcomes perihilar cholangiocarcinoma therefore still unclear whether surgical treatment intractable disease progressed methods april 1977 december 2010 total 754 consecutive patients perihilar cholangiocarcinoma treated 574 76 1 underwent resection medical records resected patients retrospectively reviewed results incidence major hepatectomies increased limited resections including central hepatectomies bile duct resections rarely performed combined vascular resection used often operative time become shorter intraoperative blood loss also decreased significantly refinements surgical techniques perioperative management morbidity decreased significantly still high rate 43 1 last 5 years mortality rate also decreased significantly p 0 001 11 1 8 72 1990 1 4 3 218 last 5 years ratio advanced disease defined pstage iva ivb increased significantly 49 4 2000 61 4 2001 disease specific survival 574 study patients including deaths 44 3 year 3 32 5 year 5 19 9 year 10 survival significantly better later period 2001 2010 earlier period 1977 2000 38 1 vs 23 1 year 5 p 0 001 pm0 r0 pn0 patients n 243 survival later period good 67 1 year 5 significantly better earlier period p 0 001 pm0 r0 pn1 patients n 142 however survival later period similar earlier period 22 1 vs 14 6 year 5 p 0 647 multivariate analysis revealed lymph node metastasis strongest prognostic indicator conclusions surgical treatment perihilar cholangiocarcinoma evolving steadily expanded surgical indication decreased mortality increased survival survival r0 pn0 patients satisfactory whereas survival pn1 patients still poor suggesting establishment effective adjuvant chemotherapy needed pubmed","probabilities":0.9799733,"Title":"Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections","Abstract":"OBJECTIVE: To review our 34-year experience with 574 consecutive resections for perihilar cholangiocarcinoma and to evaluate the progress made in surgical treatment of this disease. BACKGROUND: Few studies have reported improved surgical outcomes for perihilar cholangiocarcinoma; therefore, it is still unclear whether surgical treatment of this intractable disease has progressed. METHODS: Between April 1977 and December 2010, a total of 754 consecutive patients with perihilar cholangiocarcinoma were treated, of whom 574 (76.1%) underwent resection. The medical records of these resected patients were retrospectively reviewed. RESULTS: The incidence of major hepatectomies has increased, and limited resections, including central hepatectomies and bile duct resections, were rarely performed. Combined vascular resection was being used more often. Operative time has become shorter, and intraoperative blood loss has also decreased significantly. Because of refinements in surgical techniques and perioperative management, morbidity decreased significantly but was still high, with a rate of 43.1% in the last 5 years. Mortality rate has also decreased significantly (P < 0.001) from 11.1% (8/72) before 1990 to 1.4% (3/218) in the last 5 years. The ratio of advanced disease defined as pStage IVA and IVB has increased significantly from 49.4% before 2000 to 61.4% after 2001. The disease-specific survival for the 574 study patients (including all deaths) was 44.3% at year 3, 32.5% at year 5, and 19.9% at year 10. The survival was significantly better in the later period of 2001 to 2010 than in the earlier period of 1977 to 2000 (38.1% vs 23.1% at year 5, P < 0.001). For pM0, R0, and pN0 patients (n = 243), the survival in the later period was good with 67.1% at year 5, which was significantly better than that of the earlier period (P < 0.001). For pM0, R0, and pN1 patients (n = 142), however, the survival in the later period was similar to that of the earlier period (22.1% vs 14.6% at year 5, P = 0.647). Multivariate analysis revealed that lymph node metastasis was the strongest prognostic indicator. CONCLUSIONS: Surgical treatment of perihilar cholangiocarcinoma has been evolving steadily, with expanded surgical indication, decreased mortality, and increased survival. Survival for R0 and pN0 patients was satisfactory, whereas survival for pN1 patients was still poor, suggesting that establishment of effective adjuvant chemotherapy is needed.","Source":"PubMed","category":"HUMAN","training_data":"Evolution of surgical treatment for perihilar cholangiocarcinoma: a single-center 34-year review of 574 consecutive resections OBJECTIVE: To review our 34-year experience with 574 consecutive resections for perihilar cholangiocarcinoma and to evaluate the progress made in surgical treatment of this disease. BACKGROUND: Few studies have reported improved surgical outcomes for perihilar cholangiocarcinoma; therefore, it is still unclear whether surgical treatment of this intractable disease has progressed. METHODS: Between April 1977 and December 2010, a total of 754 consecutive patients with perihilar cholangiocarcinoma were treated, of whom 574 (76.1%) underwent resection. The medical records of these resected patients were retrospectively reviewed. RESULTS: The incidence of major hepatectomies has increased, and limited resections, including central hepatectomies and bile duct resections, were rarely performed. Combined vascular resection was being used more often. Operative time has become shorter, and intraoperative blood loss has also decreased significantly. Because of refinements in surgical techniques and perioperative management, morbidity decreased significantly but was still high, with a rate of 43.1% in the last 5 years. Mortality rate has also decreased significantly (P < 0.001) from 11.1% (8/72) before 1990 to 1.4% (3/218) in the last 5 years. The ratio of advanced disease defined as pStage IVA and IVB has increased significantly from 49.4% before 2000 to 61.4% after 2001. The disease-specific survival for the 574 study patients (including all deaths) was 44.3% at year 3, 32.5% at year 5, and 19.9% at year 10. The survival was significantly better in the later period of 2001 to 2010 than in the earlier period of 1977 to 2000 (38.1% vs 23.1% at year 5, P < 0.001). For pM0, R0, and pN0 patients (n = 243), the survival in the later period was good with 67.1% at year 5, which was significantly better than that of the earlier period (P < 0.001). For pM0, R0, and pN1 patients (n = 142), however, the survival in the later period was similar to that of the earlier period (22.1% vs 14.6% at year 5, P = 0.647). Multivariate analysis revealed that lymph node metastasis was the strongest prognostic indicator. CONCLUSIONS: Surgical treatment of perihilar cholangiocarcinoma has been evolving steadily, with expanded surgical indication, decreased mortality, and increased survival. Survival for R0 and pN0 patients was satisfactory, whereas survival for pN1 patients was still poor, suggesting that establishment of effective adjuvant chemotherapy is needed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gallbladder polypoid lesions conundrum moving forward controversy looking back gallbladder polypoid lesions gps found 5 10 general population although majority gps asymptomatic benign nature develop cancer carries poor prognosis currently risk factors natural history classification gps remain unclear differentiation benign malignant premalignant gps based available diagnostic modalities features patients gps remain difficult still evidence based guidelines dictate gps varying sizes subtypes managed facts left gps uncertainty areas covered literature search performed using terms gallbladder polyps polypoid lesion gallbladder pubmed database january 2000 september 2016 original review articles almost aspects gps humans especially diagnosis treatment surveillance reviewed analyzed reference lists reviews original articles also examined relevant publications expert commentary present article summarizes almost aspects gps analyzes controversies outlines data comments authors purpose article beneficial scientific accurate appropriate management gps pubmed","probabilities":0.9799733,"Title":"The gallbladder polypoid-lesions conundrum: moving forward with controversy by looking back","Abstract":"Gallbladder polypoid-lesions (GPs) are found in 5-10% of the general population. Although the majority of GPs are asymptomatic and benign in nature, some of them can develop into cancer, which carries a poor prognosis. Currently, the risk factors, natural history and classification of GPs remain unclear, differentiation of benign from malignant or premalignant GPs based on available diagnostic modalities and/or features of patients and GPs remain difficult, and there are still no evidence-based guidelines to dictate when and how GPs of varying sizes and subtypes should be managed. All of these facts have left GPs in uncertainty. Areas covered: A literature search was performed using the terms 'gallbladder polyps' AND 'polypoid lesion of gallbladder' in the PubMed database from January 2000 to September 2016. Original and review articles on almost all aspects of GPs in humans, especially diagnosis, treatment and surveillance, were reviewed and analyzed. Reference lists of reviews and original articles were also examined for relevant publications. Expert commentary: The present article summarizes almost all aspects of GPs, analyzes the controversies, and outlines our data and comments. It is the authors' purpose that this article be beneficial for scientific, accurate and appropriate management of GPs.","Source":"PubMed","category":"HUMAN","training_data":"The gallbladder polypoid-lesions conundrum: moving forward with controversy by looking back Gallbladder polypoid-lesions (GPs) are found in 5-10% of the general population. Although the majority of GPs are asymptomatic and benign in nature, some of them can develop into cancer, which carries a poor prognosis. Currently, the risk factors, natural history and classification of GPs remain unclear, differentiation of benign from malignant or premalignant GPs based on available diagnostic modalities and/or features of patients and GPs remain difficult, and there are still no evidence-based guidelines to dictate when and how GPs of varying sizes and subtypes should be managed. All of these facts have left GPs in uncertainty. Areas covered: A literature search was performed using the terms 'gallbladder polyps' AND 'polypoid lesion of gallbladder' in the PubMed database from January 2000 to September 2016. Original and review articles on almost all aspects of GPs in humans, especially diagnosis, treatment and surveillance, were reviewed and analyzed. Reference lists of reviews and original articles were also examined for relevant publications. Expert commentary: The present article summarizes almost all aspects of GPs, analyzes the controversies, and outlines our data and comments. It is the authors' purpose that this article be beneficial for scientific, accurate and appropriate management of GPs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinical features pancreaticobiliary maljunction introduction pancreaticobiliary maljunction pbm congenital anomaly de ned union pancreatic biliary ducts located outside duodenal wall herein investigate clinical features pbm including 2nd report japanese nationwide survey patients methods period 18 years 1990 2007 2 561 patients pbm registered 141 medical institutions japan among eligible patients n 2 529 divided two groups adult n 1 511 pediatric patients n 1 018 comparisons clinical features including associated biliary cancers performed according biliary dilatation bd age factor time era results one case pediatric patients bd combined bile duct cancer 0 1 adult patients bile duct cancer gallbladder cancer seen 6 9 13 4 patients bd 3 1 37 4 patients without bd respectively adult patients bd occurrence rates biliary cancers increased latter period 00 07 compared former period 90 99 ratio biliary cancer localization changed former latter period bile duct cancer increased latter period 5 5 9 3 conclusions largest series pbm evaluated clarify clinical features including associated biliary cancer japan nationwide survey report widely used future reference data diagnosis treatment pbm google scholar","probabilities":0.9799733,"Title":"Clinical Features Of Pancreaticobiliary Maljunction","Abstract":"Introduction Pancreaticobiliary maljunction (PBM) is a congenital anomaly, which can be defined as a union of the pancreatic and biliary ducts located outside off the duodenal wall. We herein investigate clinical features of PBM including as the 2nd report of a Japanese nationwide survey. Patients and methods During a period of 18 years (from 1990 to 2007), 2,561 patients with PBM were registered at 141 medical institutions in Japan. Among them, eligible patients (n = 2,529) were divided into two groups: adult (n = 1,511) and pediatric patients (n = 1,018). Comparisons of clinical features including associated biliary cancers were performed according to the biliary dilatation (BD), age factor, and time era. Results Only one case in pediatric patients with BD combined with a bile duct cancer (0.1 %). In adult patients, the bile duct cancer and the gallbladder cancer was seen in 6.9 and 13.4 % patients with BD and in 3.1 and 37.4 % patients without BD, respectively. In adult patients with BD, the occurrence rates of biliary cancers were increased in latter period (00’–07’) compared with former period (90’–99’). The ratio of biliary cancer localization was changed between former and latter period, and the bile duct cancer was increased in latter period (from 5.5 to 9.3 %). Conclusions The largest series of PBM were evaluated to clarify the clinical features including the associated biliary cancer in this Japan-nationwide survey. This report could be widely used in the future as a reference data for diagnosis and treatment of PBM.","Source":"Google Scholar","category":"HUMAN","training_data":"Clinical Features Of Pancreaticobiliary Maljunction Introduction Pancreaticobiliary maljunction (PBM) is a congenital anomaly, which can be defined as a union of the pancreatic and biliary ducts located outside off the duodenal wall. We herein investigate clinical features of PBM including as the 2nd report of a Japanese nationwide survey. Patients and methods During a period of 18 years (from 1990 to 2007), 2,561 patients with PBM were registered at 141 medical institutions in Japan. Among them, eligible patients (n = 2,529) were divided into two groups: adult (n = 1,511) and pediatric patients (n = 1,018). Comparisons of clinical features including associated biliary cancers were performed according to the biliary dilatation (BD), age factor, and time era. Results Only one case in pediatric patients with BD combined with a bile duct cancer (0.1 %). In adult patients, the bile duct cancer and the gallbladder cancer was seen in 6.9 and 13.4 % patients with BD and in 3.1 and 37.4 % patients without BD, respectively. In adult patients with BD, the occurrence rates of biliary cancers were increased in latter period (00’–07’) compared with former period (90’–99’). The ratio of biliary cancer localization was changed between former and latter period, and the bile duct cancer was increased in latter period (from 5.5 to 9.3 %). Conclusions The largest series of PBM were evaluated to clarify the clinical features including the associated biliary cancer in this Japan-nationwide survey. This report could be widely used in the future as a reference data for diagnosis and treatment of PBM. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"endobiliary radiofrequency ablation malignant biliary obstruction background cornerstone palliative treatment inoperable extrahepatic cholangiocarcinoma relief malignant biliary obstruction commonly applied method endoscopic stenting however procedure complicated stent obstruction respect endobiliary radiofrequency ablation may serve adjunctive tool prolonging stent patency methods patients underwent endoscopic retrograde cholangiopancreatography differential diagnosis palliative treatment diagnosis inoperable extrahepatic cholangiocarcinoma march 2011 january 2012 analyzed endobiliary radiofrequency ablation endoscopic stenting successfully performed included study technical details procedure duration stent patency length hospital stay short term morbidity mortality rate documented results seventeen patients analyzed 10 patients included study morbidity mortality rate within first 30 days procedure 20 0 respectively 2 patients mild pancreatitis occurred endobiliary procedure 1 patient endobiliary decompression achieved therefore percutaneous transhepatic biliary drainage carried median duration stent patency 9 patients successful biliary decompression 9 months range 6 15 conclusion endobiliary radiofrequency ablation seems safe feasible palliative measure may prolong stent patency overall survival patients malignant biliary obstruction due inoperable extrahepatic cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Endobiliary radiofrequency ablation for malignant biliary obstruction","Abstract":"BACKGROUND: The cornerstone of palliative treatment for inoperable extrahepatic cholangiocarcinoma is the relief of malignant biliary obstruction. The most commonly applied method is endoscopic stenting. However, the procedure can be complicated with stent obstruction. In this respect, endobiliary radiofrequency ablation may serve as an adjunctive tool for prolonging the stent patency. METHODS: Patients who underwent endoscopic retrograde cholangiopancreatography for differential diagnosis and/or palliative treatment after the diagnosis of inoperable extrahepatic cholangiocarcinoma between March 2011 and January 2012 were analyzed. Those in whom endobiliary radiofrequency ablation and endoscopic stenting was successfully performed were included in the study. Technical details of the procedure, duration of stent patency, length of hospital stay, short-term morbidity and mortality rate were documented. RESULTS: Seventeen patients were analyzed, and 10 patients were included in the study. The morbidity and mortality rate within the first 30 days after the procedure was 20% and 0%, respectively. In 2 patients, mild pancreatitis occurred because of the endobiliary procedure. In 1 patient, endobiliary decompression could not be achieved, and therefore, percutaneous transhepatic biliary drainage was carried out. The median duration of stent patency in 9 patients with successful biliary decompression was 9 months (range 6-15). CONCLUSION: Endobiliary radiofrequency ablation seems to be safe and feasible as a palliative measure and may prolong the stent patency and overall survival in patients with malignant biliary obstruction due to inoperable extrahepatic cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Endobiliary radiofrequency ablation for malignant biliary obstruction BACKGROUND: The cornerstone of palliative treatment for inoperable extrahepatic cholangiocarcinoma is the relief of malignant biliary obstruction. The most commonly applied method is endoscopic stenting. However, the procedure can be complicated with stent obstruction. In this respect, endobiliary radiofrequency ablation may serve as an adjunctive tool for prolonging the stent patency. METHODS: Patients who underwent endoscopic retrograde cholangiopancreatography for differential diagnosis and/or palliative treatment after the diagnosis of inoperable extrahepatic cholangiocarcinoma between March 2011 and January 2012 were analyzed. Those in whom endobiliary radiofrequency ablation and endoscopic stenting was successfully performed were included in the study. Technical details of the procedure, duration of stent patency, length of hospital stay, short-term morbidity and mortality rate were documented. RESULTS: Seventeen patients were analyzed, and 10 patients were included in the study. The morbidity and mortality rate within the first 30 days after the procedure was 20% and 0%, respectively. In 2 patients, mild pancreatitis occurred because of the endobiliary procedure. In 1 patient, endobiliary decompression could not be achieved, and therefore, percutaneous transhepatic biliary drainage was carried out. The median duration of stent patency in 9 patients with successful biliary decompression was 9 months (range 6-15). CONCLUSION: Endobiliary radiofrequency ablation seems to be safe and feasible as a palliative measure and may prolong the stent patency and overall survival in patients with malignant biliary obstruction due to inoperable extrahepatic cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"invasion depth measured millimeters predictor survival patients distal bile duct cancer decision tree approach background ajcc staging system unreliable predicting survival distal bile duct dbd cancer patients due inter observer variation measured depth invasion doi suggested accurate predict patients clinical outcome extra hepatic cholangiocarcinomas significance dbd cancer cutoff values still debatable study aimed identify optimal cutoff value doi relation prognosis dbd cancer patients methods data 179 patients dbd adenocarcinoma treated three institutions investigated microscopic review doi measured relationships clinicopathological parameters groups based doi 3 3 10 10 mm evaluated survival times group based doi classification compared results deeply invading tumors exhibited greater tendency toward infiltrative type high histological grade ajcc stage pancreatic duodenal lymphovascular perineural invasion measured doi significantly correlated worse relapse free overall survival p 0 05 multivariate analyses doi remained one prognostic factors p 0 05 classification significant prognostic factor new prognostic models low intermediate high risk applied doi nodal metastasis showed significant difference recurrence survival rate p 0 05 conclusions basis proposed cutoff value doi clear meaningful overcoming vagueness classification predicting clinical outcomes patients dbd carcinoma pubmed","probabilities":0.9799733,"Title":"Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach","Abstract":"BACKGROUND: AJCC staging system is unreliable for predicting survival in distal bile duct (DBD) cancer patients, due to inter-observer variation. Measured depth of invasion (DOI) is suggested to be more accurate to predict patients' clinical outcome in extra-hepatic cholangiocarcinomas, but its significance in DBD cancer and cutoff values are still debatable. This study aimed to identify the optimal cutoff value of DOI in relation to prognosis in DBD cancer patients. METHODS: Data of 179 patients with DBD adenocarcinoma treated in three institutions were investigated. Under microscopic review, DOI was measured. The relationships between the clinicopathological parameters and the groups based on DOI (≤3; 3-10; >10 mm) were evaluated, and the survival times of each group based on DOI and T classification were compared. RESULTS: Deeply invading tumors exhibited a greater tendency toward the infiltrative type, high histological grade, AJCC stage, and pancreatic, duodenal, lymphovascular and perineural invasion. The measured DOI was significantly correlated with worse relapse-free and overall survival (all p < 0.05). In multivariate analyses, the DOI remained as one of the prognostic factors (all p < 0.05), while T classification was not a significant prognostic factor. The new prognostic models (low, intermediate, and high risk) that applied DOI and nodal metastasis showed significant difference in recurrence and survival rate (all p < 0.05). CONCLUSIONS: On the basis of the proposed cutoff value, the DOI could be clear and meaningful, overcoming the vagueness of the T classification for predicting clinical outcomes in patients with DBD carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Invasion Depth Measured in Millimeters is a Predictor of Survival in Patients with Distal Bile Duct Cancer: Decision Tree Approach BACKGROUND: AJCC staging system is unreliable for predicting survival in distal bile duct (DBD) cancer patients, due to inter-observer variation. Measured depth of invasion (DOI) is suggested to be more accurate to predict patients' clinical outcome in extra-hepatic cholangiocarcinomas, but its significance in DBD cancer and cutoff values are still debatable. This study aimed to identify the optimal cutoff value of DOI in relation to prognosis in DBD cancer patients. METHODS: Data of 179 patients with DBD adenocarcinoma treated in three institutions were investigated. Under microscopic review, DOI was measured. The relationships between the clinicopathological parameters and the groups based on DOI (≤3; 3-10; >10 mm) were evaluated, and the survival times of each group based on DOI and T classification were compared. RESULTS: Deeply invading tumors exhibited a greater tendency toward the infiltrative type, high histological grade, AJCC stage, and pancreatic, duodenal, lymphovascular and perineural invasion. The measured DOI was significantly correlated with worse relapse-free and overall survival (all p < 0.05). In multivariate analyses, the DOI remained as one of the prognostic factors (all p < 0.05), while T classification was not a significant prognostic factor. The new prognostic models (low, intermediate, and high risk) that applied DOI and nodal metastasis showed significant difference in recurrence and survival rate (all p < 0.05). CONCLUSIONS: On the basis of the proposed cutoff value, the DOI could be clear and meaningful, overcoming the vagueness of the T classification for predicting clinical outcomes in patients with DBD carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"malignancies patients inflammatory bowel disease single centre experience background gastrointestinal extraintestinal malignancies long term complications patients inflammatory bowel disease ibd likely result chronic inflammation use immunosuppressive medications used control inflammation assessed frequency malignancies large tertiary ibd centre university hospital zurich methods performed retrospective analysis data 1 026 patients ibd clinic treated 2007 2014 results twenty two 1 026 patients developed 28 cases malignancies 14 patients male 8 patients female median latency ibd diagnosis first malignancy 13 years range 2 27 years common malignancies non hodgkin lymphoma colorectal cancer crc urothelial carcinoma cholangiocellular carcinoma ccc prostate cancer common tumour type crohn disease patients 13 22 lymphoma 5 cases ulcerative colitis patients 9 22 ccc 2 cases crc 2 cases observed incidence lymphoma 32 5 100 000 bladder carcinoma 21 7 100 000 ccc 10 8 100 000 higher expected known general population patients developed malignancy received immunosuppressive therapy compared cohort 927 ibd patients without malignancies statistical differences regarding gender antibodies targeting tumour necrosis factor thiopurine use conclusion data support assumption long standing disease course immunosuppressive therapy increase risk developing malignancies ibd patients pubmed","probabilities":0.9799733,"Title":"Malignancies in Patients with Inflammatory Bowel Disease: A Single-Centre Experience","Abstract":"BACKGROUND: Gastrointestinal and extraintestinal malignancies are long-term complications in patients with inflammatory bowel disease (IBD), likely as a result of chronic inflammation and the use of immunosuppressive medications used to control inflammation. Here, we assessed the frequency of malignancies in a large tertiary IBD centre at the University Hospital Zurich. METHODS: We performed a retrospective analysis of data from 1,026 patients from our IBD clinic treated between 2007 and 2014. RESULTS: Twenty two of the 1,026 patients developed 28 cases of malignancies, 14 patients were male and 8 patients female. The median latency between IBD diagnosis and first malignancy was 13 years (range 2-27 years). Most common malignancies were non-Hodgkin lymphoma, colorectal cancer (CRC), urothelial carcinoma, cholangiocellular carcinoma (CCC) and prostate cancer. The most common tumour type in Crohn's disease patients (13/22) was lymphoma (5 cases), in ulcerative colitis patients (9/22) CCC (2 cases) and CRC (2 cases). The observed incidence of lymphoma (32.5/100,000), bladder carcinoma (21.7/100,000) and CCC (10.8/100,000) was higher than expected and known from general population. All of the patients that developed a malignancy had received immunosuppressive therapy. Compared to a cohort of 927 IBD patients without malignancies there were no statistical differences regarding gender, antibodies targeting tumour necrosis factor and thiopurine use. CONCLUSION: Our data support the assumption that a long-standing disease course and immunosuppressive therapy increase the risk for developing malignancies in IBD patients.","Source":"PubMed","category":"HUMAN","training_data":"Malignancies in Patients with Inflammatory Bowel Disease: A Single-Centre Experience BACKGROUND: Gastrointestinal and extraintestinal malignancies are long-term complications in patients with inflammatory bowel disease (IBD), likely as a result of chronic inflammation and the use of immunosuppressive medications used to control inflammation. Here, we assessed the frequency of malignancies in a large tertiary IBD centre at the University Hospital Zurich. METHODS: We performed a retrospective analysis of data from 1,026 patients from our IBD clinic treated between 2007 and 2014. RESULTS: Twenty two of the 1,026 patients developed 28 cases of malignancies, 14 patients were male and 8 patients female. The median latency between IBD diagnosis and first malignancy was 13 years (range 2-27 years). Most common malignancies were non-Hodgkin lymphoma, colorectal cancer (CRC), urothelial carcinoma, cholangiocellular carcinoma (CCC) and prostate cancer. The most common tumour type in Crohn's disease patients (13/22) was lymphoma (5 cases), in ulcerative colitis patients (9/22) CCC (2 cases) and CRC (2 cases). The observed incidence of lymphoma (32.5/100,000), bladder carcinoma (21.7/100,000) and CCC (10.8/100,000) was higher than expected and known from general population. All of the patients that developed a malignancy had received immunosuppressive therapy. Compared to a cohort of 927 IBD patients without malignancies there were no statistical differences regarding gender, antibodies targeting tumour necrosis factor and thiopurine use. CONCLUSION: Our data support the assumption that a long-standing disease course and immunosuppressive therapy increase the risk for developing malignancies in IBD patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"validation study post operative mortality risk score liver resection perihilar cholangiocarcinoma background post operative mortality risk score pomrs perihilar cholangiocarcinoma phcc recently published wiggers et al j coll surg 2016 report predicted mortality 2 low risk 11 intermediate risk 37 high risk groups purpose study validate previous study results department methods pomrs calculated 203 phcc patients undergone major hepatectomy department using five clinical characteristics previous study included 287 patients results median age patients 68 41e86 years patients preoperative cholangitis future liver remnant flr 30 incomplete biliary drainage flr 50 portal vein resection 37 4 1 4 0 52 7 respectively overall post operative mortality rate 6 4 mortalities low risk n 47 intermediate risk n 99 high risk n 57 patients 2 1 7 1 8 8 respectively significant differences mortality among three groups p 0 224 conclusion significant differences pomrs among low risk intermediate risk high risk patients department google scholar","probabilities":0.9799733,"Title":"Validation Study Of The Post-Operative Mortality Risk Score After Liver Resection For Perihilar Cholangiocarcinoma","Abstract":"Background: A post-operative mortality risk score\n(POMRS) for perihilar cholangiocarcinoma (PHCC) has recently been published (Wiggers et al., J Am Coll Surg,\n2016). In this report, the predicted mortality was 2% in the\nlow-risk, 11% in the intermediate-risk, and 37% in the\nhigh-risk groups. The purpose of our study was to validate\nthe previous study results in our department.\nMethods: POMRS was calculated for 203 PHCC patients\nwho had undergone major hepatectomy in our department\nusing the five clinical characteristics from the previous\nstudy, which included 287 patients.\nResults: The median age of the patients was 68 (41e86)\nyears. Patients with preoperative cholangitis, future liver\nremnant (FLR) <30%, incomplete biliary drainage + FLR\n<50%, and portal vein resection were 37.4%, 1.4%, 0%,\nand 52.7%, respectively. The overall post-operative mortality rate was 6.4%. The mortalities in low-risk (n = 47),\nintermediate-risk (n = 99), and high-risk (n = 57) patients\nwere 2.1%, 7.1%, and 8.8%, respectively. There were no\nsignificant differences in mortality among these three\ngroups (p = 0.224).\nConclusion: There were no significant differences in the\nPOMRS among low-risk, intermediate-risk, and high-risk\npatients in our department.","Source":"Google Scholar","category":"HUMAN","training_data":"Validation Study Of The Post-Operative Mortality Risk Score After Liver Resection For Perihilar Cholangiocarcinoma Background: A post-operative mortality risk score\n(POMRS) for perihilar cholangiocarcinoma (PHCC) has recently been published (Wiggers et al., J Am Coll Surg,\n2016). In this report, the predicted mortality was 2% in the\nlow-risk, 11% in the intermediate-risk, and 37% in the\nhigh-risk groups. The purpose of our study was to validate\nthe previous study results in our department.\nMethods: POMRS was calculated for 203 PHCC patients\nwho had undergone major hepatectomy in our department\nusing the five clinical characteristics from the previous\nstudy, which included 287 patients.\nResults: The median age of the patients was 68 (41e86)\nyears. Patients with preoperative cholangitis, future liver\nremnant (FLR) <30%, incomplete biliary drainage + FLR\n<50%, and portal vein resection were 37.4%, 1.4%, 0%,\nand 52.7%, respectively. The overall post-operative mortality rate was 6.4%. The mortalities in low-risk (n = 47),\nintermediate-risk (n = 99), and high-risk (n = 57) patients\nwere 2.1%, 7.1%, and 8.8%, respectively. There were no\nsignificant differences in mortality among these three\ngroups (p = 0.224).\nConclusion: There were no significant differences in the\nPOMRS among low-risk, intermediate-risk, and high-risk\npatients in our department. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"outcome postoperative radiation therapy cholangiocarcinoma analysis dose volume histogram remnant liver aim study analyze dose volume histogram dvh remnant liver postoperative cholangiocarcinoma cca patients find toxicity rates confirm efficacy postoperative radiation therapy rt thirty two postoperative cca patients received partial liver resection postoperative rt curative intent liver reduction rate calculated contouring liver volume computed tomography ct surgery ct planning rt evaluate late toxicity radiation induced hepatic toxicity riht determined common terminology criteria adverse events toxicity grade bilirubin aspartate transaminase alanine transaminase alkaline phosphatase albumin defined 3 months rt liver metastasis revealed radiation induced liver disease rild also evaluated tumor stages distributed follows 1 ii 8 iiia 1 iiib 6 iiic 14 iva 2 median prescribed total dose 50 gy median follow time 27 months two year overall survival os 72 4 disease free survival 47 7 local control 65 3 median survival time 40 months median liver reduction rate 21 os statistically significant difference nodal status p 032 liver reduction rate 30 p 016 association grade 2 riht dvh significantly differences v30 v40 p 041 p 034 respectively grade 2 riht rates differ also significantly sex p 008 two patients 6 2 suspected rild suggest rt remnant liver considered liver v30 v40 prevent radiation induced liver dysfunction pubmed","probabilities":0.9799733,"Title":"Outcome of postoperative radiation therapy for cholangiocarcinoma and analysis of dose-volume histogram of remnant liver","Abstract":"The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The \"liver reduction rate\" was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median \"liver reduction rate\" was 21%. The OS had statistically significant difference in nodal status (P = .032) and \"liver reduction rate\" >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction.","Source":"PubMed","category":"HUMAN","training_data":"Outcome of postoperative radiation therapy for cholangiocarcinoma and analysis of dose-volume histogram of remnant liver The aim of this study was to analyze dose-volume histogram (DVH) of the remnant liver for postoperative cholangiocarcinoma (CCA) patients, to find toxicity rates, and to confirm efficacy of postoperative radiation therapy (RT).Thirty-two postoperative CCA patients received partial liver resection and postoperative RT with curative intent. The \"liver reduction rate\" was calculated by contouring liver volume at computed tomography (CT) just before the surgery and at CT for planning the RT. To evaluate late toxicity, the radiation-induced hepatic toxicity (RIHT) was determined by the common terminology criteria for adverse events toxicity grade of bilirubin, aspartate transaminase, alanine transaminase, alkaline phosphatase, and albumin, and was defined from 3 months after RT until liver metastasis was revealed. The radiation-induced liver disease (RILD) was also evaluated.Tumor stages were distributed as follows: I: 1, II: 8, IIIA: 1, IIIB: 6, IIIC: 14, IVA: 2. Median prescribed total dose was 50 Gy. Median follow-up time was 27 months. Two-year overall survival (OS): 72.4%, disease-free survival: 47.7%, local control: 65.3%, and the median survival time was 40 months. The median \"liver reduction rate\" was 21%. The OS had statistically significant difference in nodal status (P = .032) and \"liver reduction rate\" >30% (P = .016). In the association between the ≥grade 2 RIHT and DVH, there were significantly differences in V30 and V40 (P = .041, P = .034), respectively. The grade ≥2 RIHT rates differ also significantly by sex (P = .008). Two patients (6.2%) were suspected of RILD.We suggest that RT for remnant liver should be considered the liver V30, V40 to prevent radiation-induced liver dysfunction. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role surgery adjuvant therapy lymph node positive cancers gallbladder intrahepatic bile ducts background lymph node metastasis poor prognostic factor biliary tract cancers btcs optimal management patients btc positive regional lymph nodes including impact surgery adjuvant therapy unclear methods retrospective cohort study patients t1 t3n1m0 gallbladder cancer gbc intrahepatic cholangiocarcinoma ihc national cancer database 2004 2012 patients classified treatment approach nonoperative surgery surgery plus associations overall risk death treatment strategy evaluated multivariable cox regression results rates surgical resection 84 1 patients gbc n 1335 36 6 ihc n 1009 median overall survival patients nonoperative surgery surgery plus group 11 6 13 3 19 6 months respectively gbc log rank p 001 12 7 16 2 22 6 months respectively ihc log rank p 001 respectively compared nonoperative therapy surgery without associated lower risk death gbc surgery hazard ratio hr 0 59 95 confidence interval ci 0 48 0 73 surgery without hr 0 71 95 ci 0 56 0 89 ihc surgery hr 0 52 95 ci 0 42 0 63 surgery without hr 0 70 95 ci 0 56 0 87 included radiation associated lower risk death relative surgery alone patients gbc regardless margin status margin negative resection hr 0 66 95 ci 0 52 0 84 margin positive resection hr 0 54 95 ci 0 39 0 75 adjuvant chemotherapy alone patients ihc survival benefit detected adjuvant chemotherapy radiation underwent either margin positive margin negative resection conclusions best outcomes patients lymph node positive btcs associated margin negative resection gbc inclusion adjuvant chemotherapy radiation regardless margin status cancer 2018 124 74 83 2017 american cancer society pubmed","probabilities":0.9799733,"Title":"The role of surgery and adjuvant therapy in lymph node-positive cancers of the gallbladder and intrahepatic bile ducts","Abstract":"BACKGROUND: Lymph node metastasis is a poor prognostic factor for biliary tract cancers (BTCs). The optimal management of patients who have BTC with positive regional lymph nodes, including the impact of surgery and adjuvant therapy (AT), is unclear. METHODS: This was a retrospective cohort study of patients who had T1-T3N1M0 gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHC) in the National Cancer Database (2004-2012). Patients were classified by treatment approach (nonoperative, surgery, surgery plus AT). Associations between the overall risk of death and treatment strategy were evaluated with multivariable Cox regression. RESULTS: Rates of surgical resection were 84.1% for patients with GBC (n = 1335) and 36.6% for those with IHC (n = 1009). The median overall survival of patients in the nonoperative, surgery, and surgery plus AT group was 11.6, 13.3, and 19.6 months, respectively, for those with GBC (log-rank P < .001), and 12.7, 16.2, and 22.6 months, respectively, for those with IHC (log-rank P < .001), respectively. Compared with nonoperative therapy, surgery with or without AT was associated with a lower risk of death from GBC (surgery with AT: hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.48-0.73; surgery without AT: HR, 0.71; 95% CI, 0.56-0.89) and from IHC (surgery with AT: HR, 0.52; 95% CI, 0.42-0.63; surgery without AT: HR, 0.70; 95% CI, 0.56-0.87). AT that included radiation was associated with a lower risk of death relative to surgery alone for patients with GBC regardless of margin status (margin-negative resection: HR, 0.66; 95% CI, 0.52-0.84; margin-positive resection: HR, 0.54; 95% CI, 0.39-0.75), but adjuvant chemotherapy alone was not. For patients with IHC, no survival benefit was detected with adjuvant chemotherapy or radiation for those who underwent either margin-positive or margin-negative resection. CONCLUSIONS: The best outcomes for patients who have lymph node-positive BTCs are associated with margin-negative resection and, in those who have GBC, the inclusion of adjuvant chemotherapy with radiation regardless of margin status. Cancer 2018;124:74-83. © 2017 American Cancer Society.","Source":"PubMed","category":"HUMAN","training_data":"The role of surgery and adjuvant therapy in lymph node-positive cancers of the gallbladder and intrahepatic bile ducts BACKGROUND: Lymph node metastasis is a poor prognostic factor for biliary tract cancers (BTCs). The optimal management of patients who have BTC with positive regional lymph nodes, including the impact of surgery and adjuvant therapy (AT), is unclear. METHODS: This was a retrospective cohort study of patients who had T1-T3N1M0 gallbladder cancer (GBC) and intrahepatic cholangiocarcinoma (IHC) in the National Cancer Database (2004-2012). Patients were classified by treatment approach (nonoperative, surgery, surgery plus AT). Associations between the overall risk of death and treatment strategy were evaluated with multivariable Cox regression. RESULTS: Rates of surgical resection were 84.1% for patients with GBC (n = 1335) and 36.6% for those with IHC (n = 1009). The median overall survival of patients in the nonoperative, surgery, and surgery plus AT group was 11.6, 13.3, and 19.6 months, respectively, for those with GBC (log-rank P < .001), and 12.7, 16.2, and 22.6 months, respectively, for those with IHC (log-rank P < .001), respectively. Compared with nonoperative therapy, surgery with or without AT was associated with a lower risk of death from GBC (surgery with AT: hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.48-0.73; surgery without AT: HR, 0.71; 95% CI, 0.56-0.89) and from IHC (surgery with AT: HR, 0.52; 95% CI, 0.42-0.63; surgery without AT: HR, 0.70; 95% CI, 0.56-0.87). AT that included radiation was associated with a lower risk of death relative to surgery alone for patients with GBC regardless of margin status (margin-negative resection: HR, 0.66; 95% CI, 0.52-0.84; margin-positive resection: HR, 0.54; 95% CI, 0.39-0.75), but adjuvant chemotherapy alone was not. For patients with IHC, no survival benefit was detected with adjuvant chemotherapy or radiation for those who underwent either margin-positive or margin-negative resection. CONCLUSIONS: The best outcomes for patients who have lymph node-positive BTCs are associated with margin-negative resection and, in those who have GBC, the inclusion of adjuvant chemotherapy with radiation regardless of margin status. Cancer 2018;124:74-83. © 2017 American Cancer Society. PubMed","prediction_labels":"HUMAN"},{"cleaned":"analysis carcinogenic heavy metals gallstones role gallbladder carcinogenesis purpose gallstone high risk factor gallbladder pre malignancy malignancy gb pm m substances gallstones definitely assist turn gb pm m remains unclear study aimed find presence carcinogenic heavy metals gallstones explore aetiopathogenesis gallbladder pre malignancy malignancy methods presence elements gallstones detected energy dispersive x ray spectroscopy eds scanning electron microscopy sem level carcinogenic heavy metals estimated gallstones using atomic absorption spectroscopy aas experiment carried gallstone samples 46 patients gallbladder pre malignant malignant condition pm m group 65 sex age matched patients chronic cholecystitis c c group gallstones also classified three types cholesterol stone mixed stone black pigment stone results eds analysis detected presence mercury lead cobalt elements types gallstones pm m c c groups aas analysis revealed significantly higher amount mercury p 0 001 lead p 0 0001 cobalt p 0 01 cadmium p 0 01 gallstones pm m c c groups presence heavy metals also varied among stone types groups eds phase analysis showed dense deposits metals gallstones conclusions presence significantly higher amount mercury lead cobalt cadmium gallstones may play pivotal role risk factors development gallbladder malignancy pre malignancy dense deposits metals gallstones first observation may act crucial doses carcinogens stn","probabilities":0.9799733,"Title":"Analysis Of Carcinogenic Heavy Metals In Gallstones And Its Role In Gallbladder Carcinogenesis","Abstract":"Purpose: Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy. \n\n Methods: Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone. \n\n Results: EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p < 0.001), lead (p < 0.0001), cobalt (p < 0.01), and cadmium (p < 0.01) in the gallstones of PM-M than C-C groups. The presence of these heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones. \n\n Conclusions: Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens.","Source":"STN","category":"HUMAN","training_data":"Analysis Of Carcinogenic Heavy Metals In Gallstones And Its Role In Gallbladder Carcinogenesis Purpose: Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy. \n\n Methods: Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone. \n\n Results: EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p < 0.001), lead (p < 0.0001), cobalt (p < 0.01), and cadmium (p < 0.01) in the gallstones of PM-M than C-C groups. The presence of these heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones. \n\n Conclusions: Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens. STN","prediction_labels":"HUMAN"},{"cleaned":"correlation ct patterns primary intrahepatic cholangiocarcinoma time presentation metastatic spread clinical outcomes retrospective study 92 patients objective study ct appearance histopathology mass forming intrahepatic cholangiocarcinoma ihcc presentation correlate features metastatic disease patient survival materials methods irb approved hipaa compliant retrospective study reviewed pathology database 459 patients cholangiocarcinoma seen 2004 2013 identify 92 patients ihcc 48 women 44 men mean age 61 years ct scans primary tumor available review baseline follow ct reviewed two radiologists consensus record imaging characteristics metastatic patterns clinical histopathology data obtained electronic medical records imaging patterns histopathology analyzed associations metastatic spread survival results three distinct ct patterns ihcc presentation identified solitary dominant mass type ihcc n 34 dominant mass satellite nodules segment type ii ihcc n 19 multiple scattered hepatic lesions type iii ihcc n 39 distant metastases developed 49 92 patients 53 39 42 present diagnosis lungs 22 92 24 peritoneum 17 92 18 bones 13 92 14 common metastatic sites type ihcc smaller size lowest incidence metastases presentation best overall survival type iii ihcc shortest survival p 0 017 poorly differentiated ihcc higher proportion osseous metastases p 0 042 worse survival p 0 027 conclusion ihcc three distinct ct patterns presentation different prognoses knowledge patterns help radiologists detect extrahepatic disease predict prognosis pubmed","probabilities":0.9799733,"Title":"Correlation of CT patterns of primary intrahepatic cholangiocarcinoma at the time of presentation with the metastatic spread and clinical outcomes: retrospective study of 92 patients","Abstract":"OBJECTIVE: To study the CT appearance and histopathology of mass-forming intrahepatic cholangiocarcinoma (IHCC) at presentation and correlate these features with metastatic disease and patient survival. MATERIALS AND METHODS: In this IRB-approved, HIPAA compliant retrospective study, we reviewed pathology database of 459 patients with cholangiocarcinoma seen from 2004 through 2013 to identify 92 patients with IHCC (48 women, 44 men, mean age 61 years) who had CT scans of primary tumor available for review. All baseline and follow-up CT's were reviewed by two radiologists in consensus to record imaging characteristics and metastatic patterns. Clinical and histopathology data were obtained from electronic medical records. Imaging patterns and histopathology were analyzed for associations with metastatic spread and survival. RESULTS: Three distinct CT patterns of IHCC at presentation were identified: solitary dominant mass (type I IHCC, n = 34), dominant mass with satellite nodules in same segment (type II IHCC, n = 19), and multiple scattered hepatic lesions (type III IHCC, n = 39). Distant metastases developed in 49/92 patients (53%); 39 (42%) of which were present at diagnosis. Lungs (22/92; 24%), peritoneum (17/92; 18%), and bones (13/92; 14%) were most common metastatic sites. Type I IHCC had smaller size, lowest incidence of metastases at presentation, and best overall survival, while type III IHCC had shortest survival (p < 0.017). Poorly differentiated IHCC had higher proportion of osseous metastases (p = 0.042) and worse survival (p = 0.027). CONCLUSION: IHCC has three distinct CT patterns at presentation with different prognoses. Knowledge of these patterns can help radiologists to detect the extrahepatic disease and predict prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Correlation of CT patterns of primary intrahepatic cholangiocarcinoma at the time of presentation with the metastatic spread and clinical outcomes: retrospective study of 92 patients OBJECTIVE: To study the CT appearance and histopathology of mass-forming intrahepatic cholangiocarcinoma (IHCC) at presentation and correlate these features with metastatic disease and patient survival. MATERIALS AND METHODS: In this IRB-approved, HIPAA compliant retrospective study, we reviewed pathology database of 459 patients with cholangiocarcinoma seen from 2004 through 2013 to identify 92 patients with IHCC (48 women, 44 men, mean age 61 years) who had CT scans of primary tumor available for review. All baseline and follow-up CT's were reviewed by two radiologists in consensus to record imaging characteristics and metastatic patterns. Clinical and histopathology data were obtained from electronic medical records. Imaging patterns and histopathology were analyzed for associations with metastatic spread and survival. RESULTS: Three distinct CT patterns of IHCC at presentation were identified: solitary dominant mass (type I IHCC, n = 34), dominant mass with satellite nodules in same segment (type II IHCC, n = 19), and multiple scattered hepatic lesions (type III IHCC, n = 39). Distant metastases developed in 49/92 patients (53%); 39 (42%) of which were present at diagnosis. Lungs (22/92; 24%), peritoneum (17/92; 18%), and bones (13/92; 14%) were most common metastatic sites. Type I IHCC had smaller size, lowest incidence of metastases at presentation, and best overall survival, while type III IHCC had shortest survival (p < 0.017). Poorly differentiated IHCC had higher proportion of osseous metastases (p = 0.042) and worse survival (p = 0.027). CONCLUSION: IHCC has three distinct CT patterns at presentation with different prognoses. Knowledge of these patterns can help radiologists to detect the extrahepatic disease and predict prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma treated local regional therapy quantitative volumetric apparent diffusion coefficient maps assessment tumor response purpose evaluate volumetric changes apparent diffusion coefficient adc contrast material enhancement contrast enhanced ce magnetic resonance mr images hepatic arterial portal venous phases assessing early response cholangiocarcinoma treated transcatheter arterial chemoembolization tace materials methods twenty nine patients unresectable cholangiocarcinoma including 11 men mean age 60 years standard deviation 16 8 18 women mean age 63 years standard deviation 11 5 included retrospective institutional review board approved hipaa compliant study informed consent waived sixty nine tace procedures performed observational time range one five tace sessions patients received another form therapy treatment tace mr imaging performed 3 4 weeks tace images analyzed semiautomatic volumetric software package patients stratified responders nonresponders basis overall survival os primary end point differences responders nonresponders analyzed paired tests os calculated kaplan meier method significant differences analyzed log rank test results mean volumetric adc increased 1 54 10 3 mm2 sec 1 92 10 3 mm2 sec p 0001 significant decrease mean volumetric enhancement hepatic arterial 40 6 vs 37 5 p 546 portal venous 79 0 vs 70 0 p 105 phases patients demonstrated improved survival 10 months significant increase mean volumetric adc volumetric adc threshold level 1 60 10 3 mm2 sec p 002 patients 45 greater n 21 log rank test p 02 60 greater n 12 log rank test p 009 adc changes whole tumor volume demonstrated better os compared patients adc changes achieved conclusion patients percentage tumor volume increase adc 45 greater 60 greater threshold level 1 60 10 3 mm2 sec favorable response therapy improved survival pubmed","probabilities":0.9799733,"Title":"Intrahepatic cholangiocarcinoma treated with local-regional therapy: quantitative volumetric apparent diffusion coefficient maps for assessment of tumor response","Abstract":"PURPOSE: To evaluate volumetric changes in apparent diffusion coefficient (ADC) and contrast material enhancement on contrast-enhanced (CE) magnetic resonance (MR) images in hepatic arterial and portal venous phases for assessing early response in cholangiocarcinoma treated with transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Twenty-nine patients with unresectable cholangiocarcinoma, including 11 men (mean age, 60 years; standard deviation, 16.8) and 18 women (mean age, 63 years; standard deviation, 11.5) were included in this retrospective institutional review board-approved, HIPAA-compliant study; informed consent was waived. Sixty-nine TACE procedures were performed during the observational time (range, one to five TACE sessions). No patients received another form of therapy after treatment with TACE. MR Imaging was performed before and 3-4 weeks after TACE, and images were analyzed with a semiautomatic volumetric software package. Patients were stratified as responders and nonresponders on the basis of overall survival (OS) as the primary end point. Differences between responders and nonresponders were analyzed with paired t tests, and OS was calculated with the Kaplan-Meier method. Significant differences were analyzed with the log-rank test. RESULTS: Mean volumetric ADC increased from 1.54×10(-3) mm2/sec to 1.92×10(-3) mm2/sec (P<.0001), with no significant decrease in mean volumetric enhancement in hepatic arterial (40.6% vs 37.5%, P=.546) and portal venous (79.0% vs 70.0%, P=.105) phases. Patients who demonstrated improved survival of 10 months or more had a significant increase in mean volumetric ADC and volumetric ADC above the threshold level of 1.60×10(-3) mm2/sec (P<.002). Patients with 45% or greater (n=21; log-rank test, P<.02) and 60% or greater (n=12; log-rank test, P<.009) ADC changes for the whole tumor volume demonstrated better OS compared with patients in whom these ADC changes were not achieved. CONCLUSION: Patients with percentage tumor volume increase in ADC of 45% or greater and 60% or greater above the threshold level of 1.60×10(-3) mm2/sec had favorable response to therapy and improved survival.","Source":"PubMed","category":"HUMAN","training_data":"Intrahepatic cholangiocarcinoma treated with local-regional therapy: quantitative volumetric apparent diffusion coefficient maps for assessment of tumor response PURPOSE: To evaluate volumetric changes in apparent diffusion coefficient (ADC) and contrast material enhancement on contrast-enhanced (CE) magnetic resonance (MR) images in hepatic arterial and portal venous phases for assessing early response in cholangiocarcinoma treated with transcatheter arterial chemoembolization (TACE). MATERIALS AND METHODS: Twenty-nine patients with unresectable cholangiocarcinoma, including 11 men (mean age, 60 years; standard deviation, 16.8) and 18 women (mean age, 63 years; standard deviation, 11.5) were included in this retrospective institutional review board-approved, HIPAA-compliant study; informed consent was waived. Sixty-nine TACE procedures were performed during the observational time (range, one to five TACE sessions). No patients received another form of therapy after treatment with TACE. MR Imaging was performed before and 3-4 weeks after TACE, and images were analyzed with a semiautomatic volumetric software package. Patients were stratified as responders and nonresponders on the basis of overall survival (OS) as the primary end point. Differences between responders and nonresponders were analyzed with paired t tests, and OS was calculated with the Kaplan-Meier method. Significant differences were analyzed with the log-rank test. RESULTS: Mean volumetric ADC increased from 1.54×10(-3) mm2/sec to 1.92×10(-3) mm2/sec (P<.0001), with no significant decrease in mean volumetric enhancement in hepatic arterial (40.6% vs 37.5%, P=.546) and portal venous (79.0% vs 70.0%, P=.105) phases. Patients who demonstrated improved survival of 10 months or more had a significant increase in mean volumetric ADC and volumetric ADC above the threshold level of 1.60×10(-3) mm2/sec (P<.002). Patients with 45% or greater (n=21; log-rank test, P<.02) and 60% or greater (n=12; log-rank test, P<.009) ADC changes for the whole tumor volume demonstrated better OS compared with patients in whom these ADC changes were not achieved. CONCLUSION: Patients with percentage tumor volume increase in ADC of 45% or greater and 60% or greater above the threshold level of 1.60×10(-3) mm2/sec had favorable response to therapy and improved survival. PubMed","prediction_labels":"HUMAN"},{"cleaned":"management outcomes patients recurrent intrahepatic cholangiocarcinoma following previous curative intent surgical resection background management outcomes patients recurrent intrahepatic cholangiocarcinoma icc following curative intent surgery well documented sought characterize treatment patients recurrent icc define therapy specific outcomes methods patients underwent surgery icc 1990 2013 identified international database data clinicopathological characteristics operative details recurrence recurrence related management recorded analyzed results total 563 patients undergoing curative intent hepatic resection icc met inclusion criteria identified median follow 19 months 400 71 0 patients developed recurrence initial surgery treatment resection 98 8 resection ablation 1 2 overall 5 year survival 23 6 400 71 0 patients recurred median disease free survival 11 2 months first recurrence site intrahepatic 59 8 extrahepatic 14 5 intra extrahepatic 25 7 overall 210 52 5 patients received best supportive care bsc whereas 190 47 5 patients received treatment systemic chemotherapy 24 2 repeat liver directed therapy systemic chemotherapy 75 8 repeat liver directed therapy consisted repeat hepatic resection ablation 28 5 ablation alone 18 7 intra arterial therapy iat 52 8 among patients recurred median survival time recurrence 11 1 months bsc 8 0 months systemic chemotherapy 16 8 months liver directed therapy 18 0 months median survival patients undergoing resection recurrent icc 26 7 months versus 9 6 months patients iat p 0 001 conclusions recurrence following resection icc common occurring two thirds patients recurrence prognosis poor 9 patients underwent repeat liver resection recurrence offered modest survival benefit pubmed","probabilities":0.9799733,"Title":"Management and Outcomes of Patients with Recurrent Intrahepatic Cholangiocarcinoma Following Previous Curative-Intent Surgical Resection","Abstract":"BACKGROUND: Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. METHODS: Patients who underwent surgery for ICC from 1990 to 2013 were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence, and recurrence-related management were recorded and analyzed. RESULTS: A total of 563 patients undergoing curative-intent hepatic resection for ICC who met the inclusion criteria were identified. With a median follow-up of 19 months, 400 (71.0 %) patients developed a recurrence. At initial surgery, treatment was resection only (98.8 %) or resection + ablation (1.2 %). Overall 5-year survival was 23.6 %; 400 (71.0 %) patients recurred with a median disease-free survival of 11.2 months. First recurrence site was intrahepatic only (59.8 %), extrahepatic only (14.5 %), or intra- and extrahepatic (25.7 %). Overall, 210 (52.5 %) patients received best supportive care (BSC), whereas 190 (47.5 %) patients received treatment, such as systemic chemotherapy-only (24.2 %) or repeat liver-directed therapy ± systemic chemotherapy (75.8 %). Repeat liver-directed therapy consisted of repeat hepatic resection ± ablation (28.5 %), ablation alone (18.7 %), and intra-arterial therapy (IAT) (52.8 %). Among patients who recurred, median survival from the time of the recurrence was 11.1 months (BSC 8.0 months, systemic chemotherapy-only 16.8 months, liver-directed therapy 18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 9.6 months for patients who had IAT (p < 0.001). CONCLUSIONS: Recurrence following resection of ICC was common, occurring in up to two-thirds of patients. When there is recurrence, prognosis is poor. Only 9 % of patients underwent repeat liver resection after recurrence, which offered a modest survival benefit.","Source":"PubMed","category":"HUMAN","training_data":"Management and Outcomes of Patients with Recurrent Intrahepatic Cholangiocarcinoma Following Previous Curative-Intent Surgical Resection BACKGROUND: Management and outcomes of patients with recurrent intrahepatic cholangiocarcinoma (ICC) following curative-intent surgery are not well documented. We sought to characterize the treatment of patients with recurrent ICC and define therapy-specific outcomes. METHODS: Patients who underwent surgery for ICC from 1990 to 2013 were identified from an international database. Data on clinicopathological characteristics, operative details, recurrence, and recurrence-related management were recorded and analyzed. RESULTS: A total of 563 patients undergoing curative-intent hepatic resection for ICC who met the inclusion criteria were identified. With a median follow-up of 19 months, 400 (71.0 %) patients developed a recurrence. At initial surgery, treatment was resection only (98.8 %) or resection + ablation (1.2 %). Overall 5-year survival was 23.6 %; 400 (71.0 %) patients recurred with a median disease-free survival of 11.2 months. First recurrence site was intrahepatic only (59.8 %), extrahepatic only (14.5 %), or intra- and extrahepatic (25.7 %). Overall, 210 (52.5 %) patients received best supportive care (BSC), whereas 190 (47.5 %) patients received treatment, such as systemic chemotherapy-only (24.2 %) or repeat liver-directed therapy ± systemic chemotherapy (75.8 %). Repeat liver-directed therapy consisted of repeat hepatic resection ± ablation (28.5 %), ablation alone (18.7 %), and intra-arterial therapy (IAT) (52.8 %). Among patients who recurred, median survival from the time of the recurrence was 11.1 months (BSC 8.0 months, systemic chemotherapy-only 16.8 months, liver-directed therapy 18.0 months). The median survival of patients undergoing resection of recurrent ICC was 26.7 months versus 9.6 months for patients who had IAT (p < 0.001). CONCLUSIONS: Recurrence following resection of ICC was common, occurring in up to two-thirds of patients. When there is recurrence, prognosis is poor. Only 9 % of patients underwent repeat liver resection after recurrence, which offered a modest survival benefit. PubMed","prediction_labels":"HUMAN"},{"cleaned":"obesity epidemiological perspective asia relationship gastrointestinal liver cancers obesity major health problem asia pacific region proportion people overweight obese region increased dramatically closely linked increasing affluence region body mass index used yardstick many published studies noted asian patients greater percentage body fat given body mass index especially abdominal visceral obesity association obesity cancers intriguing worrisome time obesity rising exponentially throughout world especially asia pacific region evidence association gastrointestinal cancers well documented reported cardioesophageal colorectal liver pancreatic gallbladder cancers strength association varies individual cancers particular concern colorectal cancer perhaps fastest emerging cancer region biological mechanisms obesity related carcinogenesis described includes insulin resistance secretion adipokines chronic inflammation dose response relationship severity excess body weight risks cancer reported however paucity data looking decrease incidence cancers decrease body weight treatment example bariatric surgery studies difficult perform require long period longitudinal follow pubmed","probabilities":0.9799733,"Title":"Obesity: an epidemiological perspective from Asia and its relationship to gastrointestinal and liver cancers","Abstract":"Obesity is major health problem in the Asia-Pacific region. The proportion of people who are overweight and obese in the region has increased dramatically and is closely linked to the increasing affluence in the region. While the body mass index has been used as a yardstick in many published studies, it has been noted that Asian patients have a greater percentage body fat for a given body mass index and especially abdominal or visceral obesity. The association of obesity and cancers is intriguing and worrisome at the same time, as obesity is rising exponentially throughout the world especially in the Asia-Pacific region. Evidence of its association with gastrointestinal cancers is well documented and is reported with cardioesophageal, colorectal, liver, pancreatic, and gallbladder cancers. The strength of association varies between individual cancers but is of particular concern with colorectal cancer, which is perhaps the fastest emerging cancer in this region. Biological mechanisms for obesity-related carcinogenesis have been described, which includes insulin resistance and secretion of adipokines and chronic inflammation. A \"dose-response\" relationship between severity of excess body weight and risks of cancer has been reported. However, there is a paucity of data looking at a decrease in incidence of these cancers with a decrease in body weight with treatment, for example, bariatric surgery. Such studies will be difficult to perform and which would require a long period of longitudinal follow-up.","Source":"PubMed","category":"HUMAN","training_data":"Obesity: an epidemiological perspective from Asia and its relationship to gastrointestinal and liver cancers Obesity is major health problem in the Asia-Pacific region. The proportion of people who are overweight and obese in the region has increased dramatically and is closely linked to the increasing affluence in the region. While the body mass index has been used as a yardstick in many published studies, it has been noted that Asian patients have a greater percentage body fat for a given body mass index and especially abdominal or visceral obesity. The association of obesity and cancers is intriguing and worrisome at the same time, as obesity is rising exponentially throughout the world especially in the Asia-Pacific region. Evidence of its association with gastrointestinal cancers is well documented and is reported with cardioesophageal, colorectal, liver, pancreatic, and gallbladder cancers. The strength of association varies between individual cancers but is of particular concern with colorectal cancer, which is perhaps the fastest emerging cancer in this region. Biological mechanisms for obesity-related carcinogenesis have been described, which includes insulin resistance and secretion of adipokines and chronic inflammation. A \"dose-response\" relationship between severity of excess body weight and risks of cancer has been reported. However, there is a paucity of data looking at a decrease in incidence of these cancers with a decrease in body weight with treatment, for example, bariatric surgery. Such studies will be difficult to perform and which would require a long period of longitudinal follow-up. PubMed","prediction_labels":"HUMAN"},{"cleaned":"enhancer zeste homolog 2 ezh2 regulates tumor angiogenesis predicts recurrence prognosis intrahepatic cholangiocarcinoma background enhancer zeste homolog 2 ezh2 catalytic subunit polycomb repressive complex 2 prc2 regulates tumor malignancy gene silencing via histone methylation study investigate role ezh2 angiogenesis intrahepatic cholangiocarcinoma icc methods influence ezh2 tumor angiogenesis examined bioinformatics analysis public database also assessed correlation ezh2 vasohibin 1 vash1 expression 47 patients icc immunohistochemical ihc staining vitro gene silencing assays prognostic significance ezh2 vash1 expression ihc also examined icc cohort results bioinformatics analysis showed ezh2 associated several angiogenesis gene sets public database ezh2 suppressed vash1 expression vitro assays ihc studies ezh2 high vash1 low status independently associated poor disease free survival p 0 019 poor overall survival p 0 0055 conclusion current study demonstrated high ezh2 expression associated activation tumor angiogenesis activation ezh2 mediated angiogenesis pathway predicted prognosis patients icc pubmed","probabilities":0.5555556,"Title":"Enhancer of zeste homolog 2 (EZH2) regulates tumor angiogenesis and predicts recurrence and prognosis of intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and regulates tumor malignancy by gene silencing via histone methylation. In this study we investigate the role of EZH2 in angiogenesis of intrahepatic cholangiocarcinoma (ICC). METHODS: The influence of EZH2 on tumor angiogenesis was examined by bioinformatics analysis of a public database. We also assessed the correlation between EZH2 and vasohibin 1 (VASH1) expression in 47 patients with ICC by immunohistochemical (IHC) staining and in vitro gene silencing assays. The prognostic significance of EZH2 and VASH1 expression by IHC was also examined in the ICC cohort. RESULTS: Bioinformatics analysis showed that EZH2 was associated with several angiogenesis gene sets in the public database. EZH2 suppressed VASH1 expression in in vitro assays and IHC studies. EZH2-high/VASH1-low status was independently associated with poor disease-free survival (P = 0.019) and poor overall survival (P = 0.0055). CONCLUSION: The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC.","Source":"PubMed","category":"ANIMAL","training_data":"Enhancer of zeste homolog 2 (EZH2) regulates tumor angiogenesis and predicts recurrence and prognosis of intrahepatic cholangiocarcinoma BACKGROUND: Enhancer of zeste homolog 2 (EZH2) is the catalytic subunit of the polycomb repressive complex 2 (PRC2) and regulates tumor malignancy by gene silencing via histone methylation. In this study we investigate the role of EZH2 in angiogenesis of intrahepatic cholangiocarcinoma (ICC). METHODS: The influence of EZH2 on tumor angiogenesis was examined by bioinformatics analysis of a public database. We also assessed the correlation between EZH2 and vasohibin 1 (VASH1) expression in 47 patients with ICC by immunohistochemical (IHC) staining and in vitro gene silencing assays. The prognostic significance of EZH2 and VASH1 expression by IHC was also examined in the ICC cohort. RESULTS: Bioinformatics analysis showed that EZH2 was associated with several angiogenesis gene sets in the public database. EZH2 suppressed VASH1 expression in in vitro assays and IHC studies. EZH2-high/VASH1-low status was independently associated with poor disease-free survival (P = 0.019) and poor overall survival (P = 0.0055). CONCLUSION: The current study demonstrated that high EZH2 expression was associated with activation of tumor angiogenesis, and activation of the EZH2-mediated angiogenesis pathway predicted the prognosis of patients with ICC. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"immunohistochemical evidence prognostic value hedgehog pathway components primary gallbladder carcinoma purpose activation hedgehog hh pathways studied extensively many malignant tumors elucidate clinical diagnostic prognostic utilities however roles primary gallbladder carcinoma gbc remain poorly understood study conducted clarify immunoreactivity prognostic value hh pathway components gbc methods levels sonic hedgehog shh receptor patched ptch1 downstream transcription factor gli1 protein measured immunohistochemistry 93 specimens patients gbc analyzed correlations expression factors clinicopathological features including prognosis results among 93 gbc specimens 76 81 7 70 75 3 66 70 0 positive shh ptch1 gli1 expression respectively expressions significantly correlated stage lymph node metastasis venous invasion hepatic infiltration lymphatic invasion p 0 05 patients positive staining shh ptch1 gli1 significantly lower survival rates patients negative staining expression patterns shh ptch1 gli1 associated malignant behavior risk category gbc conclusions knowledge first report define role hh pathway gbc shh ptch1 gli1 frequently expressed gbc associated poorer survival thus high expressions shh ptch1 gli1 proteins serve auxiliary parameters predicting malignant behavior gbc pubmed","probabilities":0.9799733,"Title":"Immunohistochemical evidence of the prognostic value of hedgehog pathway components in primary gallbladder carcinoma","Abstract":"PURPOSE: The activation of hedgehog (Hh) pathways has been studied extensively in many malignant tumors to elucidate their clinical diagnostic and prognostic utilities. However, their roles in primary gallbladder carcinoma (GBC) remain poorly understood. This study was conducted to clarify the immunoreactivity and prognostic value of Hh pathway components in GBC. METHODS: Levels of sonic hedgehog (Shh), its receptor, Patched (Ptch1), and its downstream transcription factor, Gli1 protein, were measured by immunohistochemistry in 93 specimens from patients with GBC. We analyzed the correlations between the expression of these factors and clinicopathological features, including prognosis. RESULTS: Among the 93 GBC specimens, 76 (81.7%), 70 (75.3%) and 66 (70.0%) were positive for Shh, Ptch1 and Gli1 expression, respectively. Expressions were significantly correlated with stage, lymph node metastasis, venous invasion, hepatic infiltration and lymphatic invasion (all P < 0.05). Patients with positive staining for Shh, Ptch1 and Gli1 had significantly lower survival rates than patients with negative staining. The expression patterns of Shh, Ptch1 and Gli1 were all associated with a malignant behavior risk category in GBC. CONCLUSIONS: To our knowledge, this is the first report to define the role of the Hh pathway in GBC. Shh, Ptch1 and Gli1 are frequently expressed in GBC and associated with poorer survival. Thus, high expressions of Shh, Ptch1 and Gli1 proteins could serve as auxiliary parameters for predicting the malignant behavior of GBC.","Source":"PubMed","category":"HUMAN","training_data":"Immunohistochemical evidence of the prognostic value of hedgehog pathway components in primary gallbladder carcinoma PURPOSE: The activation of hedgehog (Hh) pathways has been studied extensively in many malignant tumors to elucidate their clinical diagnostic and prognostic utilities. However, their roles in primary gallbladder carcinoma (GBC) remain poorly understood. This study was conducted to clarify the immunoreactivity and prognostic value of Hh pathway components in GBC. METHODS: Levels of sonic hedgehog (Shh), its receptor, Patched (Ptch1), and its downstream transcription factor, Gli1 protein, were measured by immunohistochemistry in 93 specimens from patients with GBC. We analyzed the correlations between the expression of these factors and clinicopathological features, including prognosis. RESULTS: Among the 93 GBC specimens, 76 (81.7%), 70 (75.3%) and 66 (70.0%) were positive for Shh, Ptch1 and Gli1 expression, respectively. Expressions were significantly correlated with stage, lymph node metastasis, venous invasion, hepatic infiltration and lymphatic invasion (all P < 0.05). Patients with positive staining for Shh, Ptch1 and Gli1 had significantly lower survival rates than patients with negative staining. The expression patterns of Shh, Ptch1 and Gli1 were all associated with a malignant behavior risk category in GBC. CONCLUSIONS: To our knowledge, this is the first report to define the role of the Hh pathway in GBC. Shh, Ptch1 and Gli1 are frequently expressed in GBC and associated with poorer survival. Thus, high expressions of Shh, Ptch1 and Gli1 proteins could serve as auxiliary parameters for predicting the malignant behavior of GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prothymosin parathymosin expression predicts poor prognosis squamous adenosquamous carcinomas gallbladder present study aimed investigate expression patterns prothymosin ptma parathymosin ptms patients squamous cell carcinoma scc adenosquamous cell carcinoma asc adenocarcinoma ac gallbladder assess association clinicopathological characteristics prognosis patients retrospective analysis data pertaining patients scc asc n 46 ac n 80 gallbladder treated surgical resection conducted kaplan meier survival analysis also performed assess correlation expression pattern survival results revealed higher percentage patients large tumor diameter 3 cm scc asc group compared ac group p 0 05 significant differences observed patients scc asc ac respect patient sex presence gallstones tnm stage lymph node metastasis invasive growth anatomically contiguous structures surgical methods used survival rate expression levels ptma ptma p 0 05 however positive expression ptma ptma associated tumor size tnm stage lymph node metastasis locally invasive growth treatment radical resection patients scc asc ac p 0 05 addition positive expression ptma ptma observed significantly lower number patients advanced ac compared early ac p 0 05 expression levels also associated shorter survival scc asc group ac group p 0 05 cox multivariate analysis also demonstrated negative correlation ptma ptma levels postoperative survival rate two groups conclusion present study indicated expression levels ptma ptma closely associated tumorigenesis progression scc asc ac gallbladder positive expression ptma ptma may serve valuable prognostic factor patients stn","probabilities":1.0,"Title":"Prothymosin-A And Parathymosin Expression Predicts Poor Prognosis In Squamous And Adenosquamous Carcinomas Of The Gallbladder","Abstract":"The present study aimed to investigate the expression patterns of prothymosin-α (PTMA) and parathymosin (PTMS) in patients with squamous cell carcinoma (SCC), adenosquamous cell carcinoma (ASC) and adenocarcinoma (AC) of the gallbladder, and to assess their association with the clinicopathological characteristics and prognosis of the patients. A retrospective analysis of data pertaining to patients with SCC/ASC (n=46) and AC (n=80) of the gallbladder, who were treated with surgical resection, was conducted. Kaplan-Meier survival analysis was also performed to assess the correlation of the expression pattern with survival. The results revealed a higher percentage of patients with a large tumor diameter (>3 cm) in the SCC/ASC group as compared with those in the AC group (P<0.05). No significant differences were observed between patients with SCC/ASC and those with AC with respect to the patient sex, presence of gallstones, TNM stage, lymph node metastasis, invasive growth into anatomically contiguous structures, surgical methods used, survival rate, and the expression levels of PTMA and PTMA (P>0.05). However, positive expression of PTMA and PTMA was associated with tumor size, TNM stage, lymph node metastasis, locally invasive growth, and treatment with radical resection in patients with SCC/ASC and AC (P<0.05). In addition, positive expression of PTMA and PTMA was observed in a significantly lower number of patients with advanced AC as compared with those in early AC (P<0.05), while these expression levels were also associated with shorter survival in the SCC/ASC group and AC group (P<0.05). Cox multivariate analysis also demonstrated a negative correlation between PTMA and PTMA levels, and the postoperative survival rate in the two groups. In conclusion, the present study indicated that the expression levels of PTMA and PTMA were closely associated with the tumorigenesis and progression of SCC, ASC and AC of the gallbladder. Positive expression of PTMA and PTMA may serve as a valuable prognostic factor in these patients.","Source":"STN","category":"HUMAN","training_data":"Prothymosin-A And Parathymosin Expression Predicts Poor Prognosis In Squamous And Adenosquamous Carcinomas Of The Gallbladder The present study aimed to investigate the expression patterns of prothymosin-α (PTMA) and parathymosin (PTMS) in patients with squamous cell carcinoma (SCC), adenosquamous cell carcinoma (ASC) and adenocarcinoma (AC) of the gallbladder, and to assess their association with the clinicopathological characteristics and prognosis of the patients. A retrospective analysis of data pertaining to patients with SCC/ASC (n=46) and AC (n=80) of the gallbladder, who were treated with surgical resection, was conducted. Kaplan-Meier survival analysis was also performed to assess the correlation of the expression pattern with survival. The results revealed a higher percentage of patients with a large tumor diameter (>3 cm) in the SCC/ASC group as compared with those in the AC group (P<0.05). No significant differences were observed between patients with SCC/ASC and those with AC with respect to the patient sex, presence of gallstones, TNM stage, lymph node metastasis, invasive growth into anatomically contiguous structures, surgical methods used, survival rate, and the expression levels of PTMA and PTMA (P>0.05). However, positive expression of PTMA and PTMA was associated with tumor size, TNM stage, lymph node metastasis, locally invasive growth, and treatment with radical resection in patients with SCC/ASC and AC (P<0.05). In addition, positive expression of PTMA and PTMA was observed in a significantly lower number of patients with advanced AC as compared with those in early AC (P<0.05), while these expression levels were also associated with shorter survival in the SCC/ASC group and AC group (P<0.05). Cox multivariate analysis also demonstrated a negative correlation between PTMA and PTMA levels, and the postoperative survival rate in the two groups. In conclusion, the present study indicated that the expression levels of PTMA and PTMA were closely associated with the tumorigenesis and progression of SCC, ASC and AC of the gallbladder. Positive expression of PTMA and PTMA may serve as a valuable prognostic factor in these patients. STN","prediction_labels":"HUMAN"},{"cleaned":"elevated neutrophil lymphocyte ratio independent poor prognostic factor patients intrahepatic cholangiocarcinoma investigated whether elevated neutrophil lymphocyte ratio nlr associated poor anti tumor immunity prognosis patients intrahepatic cholangiocarcinoma icc clinicopathologic data 102 patients icc underwent hepatectomy retrospectively analyzed kaplan meier method cox regression model used analyze survival prognosis percentage overall lymphocytes cells cd8 cells high nlr group lower low nlr group percentage pd 1 cd4 pd 1 cd8 cells higher percentage ifn cd4 ifn cd8 cells lower high nlr group low nlr group p 0 045 p 0 008 p 0 012 p 0 006 density tumor infiltrating cd3 cells high nlr group lower low nlr group p 0 001 elevated nlr independent predictor poor overall survival os p 0 035 recurrence free survival rfs p 0 008 results indicate elevated nlr associated poor anti tumor immunity poor biomarker prognosis patients icc pubmed","probabilities":0.9799733,"Title":"Elevated neutrophil-to-lymphocyte ratio is an independent poor prognostic factor in patients with intrahepatic cholangiocarcinoma","Abstract":"We investigated whether elevated neutrophil-to-lymphocyte ratio ( NLR ) was associated with poor anti-tumor immunity and prognosis in patients with intrahepatic cholangiocarcinoma ( ICC ). Clinicopathologic data of 102 patients with ICC who underwent hepatectomy was retrospectively analyzed. The Kaplan-Meier method and Cox regression model were used to analyze the survival and prognosis. The percentage of overall lymphocytes , T cells and CD8+ T cells in the high NLR group was lower than that in the low NLR group. The percentage of PD-1+CD4+ and PD-1+CD8+ T cells was higher and the percentage of IFN-γ+CD4+ and IFN-γ+CD8+ T cells was lower in the high NLR group than that in the low NLR group ( p = 0.045, p = 0.008; p = 0.012, p = 0.006 ). Density of tumor-infiltrating CD3+ T cells in the high NLR group was lower than that in the low NLR group ( p < 0.001 ). Elevated NLR was an independent predictor for poor overall survival ( OS; p = 0.035 ) and recurrence-free survival ( RFS; p = 0.008 ). These results indicate that elevated NLR is associated with poor anti-tumor immunity and could be a poor biomarker for prognosis in patients with ICC.","Source":"PubMed","category":"HUMAN","training_data":"Elevated neutrophil-to-lymphocyte ratio is an independent poor prognostic factor in patients with intrahepatic cholangiocarcinoma We investigated whether elevated neutrophil-to-lymphocyte ratio ( NLR ) was associated with poor anti-tumor immunity and prognosis in patients with intrahepatic cholangiocarcinoma ( ICC ). Clinicopathologic data of 102 patients with ICC who underwent hepatectomy was retrospectively analyzed. The Kaplan-Meier method and Cox regression model were used to analyze the survival and prognosis. The percentage of overall lymphocytes , T cells and CD8+ T cells in the high NLR group was lower than that in the low NLR group. The percentage of PD-1+CD4+ and PD-1+CD8+ T cells was higher and the percentage of IFN-γ+CD4+ and IFN-γ+CD8+ T cells was lower in the high NLR group than that in the low NLR group ( p = 0.045, p = 0.008; p = 0.012, p = 0.006 ). Density of tumor-infiltrating CD3+ T cells in the high NLR group was lower than that in the low NLR group ( p < 0.001 ). Elevated NLR was an independent predictor for poor overall survival ( OS; p = 0.035 ) and recurrence-free survival ( RFS; p = 0.008 ). These results indicate that elevated NLR is associated with poor anti-tumor immunity and could be a poor biomarker for prognosis in patients with ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"elevation serum glutamyltransferase predictor aggressive tumor behaviors unfavorable prognosis patients intrahepatic cholangiocarcinoma analysis large monocenter study objective glutamyltransferase ggt used diagnostic biomarker hepatobiliary disease however little known role intrahepatic cholangiocarcinoma icc aim present study validate clinical significance ggt predicting prognosis icc patients materials methods total 411 patients pathologically confirmed icc retrospectively analyzed 307 patients underwent hepatectomy 64 patients unresectable tumors treated chemotherapy n 42 transcatheter arterial chemoembolization n 22 40 patients end stage disease received supportive treatment association ggt clinicopathological features prognosis assessed results serum ggt levels significantly associated hepatitis b infection p 0 02 child pugh grade p 0 02 vascular invasion p 0 001 lymph node involvement p 0 04 incomplete tumor encapsulation p 0 009 survival analysis showed ggt independent predictor poor prognosis hazard ratio 2 36 95 confidence interval 1 67 3 34 p 0 001 prognostic value ggt validated mass forming normal bilirubin child pugh subgroups subsequent recurrence analysis showed recurrence free survival patients high ggt levels significantly shorter low ggt levels 6 vs 12 months p 0 001 serum ggt level independent predictor tumor recurrence icc patients hazard ratio 1 59 95 confidence interval 1 07 2 37 p 0 02 conclusion elevation serum ggt levels indicator aggressive tumor behaviors predictor poor clinical outcomes may prove useful biomarker identifying icc patients high risk early recurrence unfavorable prognosis pubmed","probabilities":0.9799733,"Title":"Elevation of serum γ-glutamyltransferase as a predictor of aggressive tumor behaviors and unfavorable prognosis in patients with intrahepatic cholangiocarcinoma: analysis of a large monocenter study","Abstract":"OBJECTIVE: γ-Glutamyltransferase (GGT) has been used as a diagnostic biomarker for hepatobiliary disease. However, little is known about its role in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to validate the clinical significance of GGT in predicting the prognosis of ICC patients. MATERIALS AND METHODS: A total of 411 patients with pathologically confirmed ICC were retrospectively analyzed. Of them, 307 patients underwent hepatectomy, 64 patients with unresectable tumors were treated with chemotherapy (n=42) or transcatheter arterial chemoembolization (n=22), and 40 patients with end-stage disease received supportive treatment. The association between GGT and the clinicopathological features and prognosis was assessed. RESULTS: Serum GGT levels were significantly associated with hepatitis B infection (P=0.02), the Child-Pugh grade (P=0.02), vascular invasion (P<0.001), lymph node involvement (P=0.04), and incomplete tumor encapsulation (P=0.009). Survival analysis showed that GGT was an independent predictor of a poor prognosis (hazard ratio=2.36, 95% confidence interval: 1.67-3.34, P=0.001). This prognostic value of GGT was further validated in the mass-forming, normal bilirubin, and Child-Pugh A subgroups. Subsequent recurrence analysis showed that a recurrence-free survival in patients with high GGT levels was significantly shorter than that in those with low GGT levels (6 vs. 12 months, P<0.001). The serum GGT level was an independent predictor of tumor recurrence in ICC patients (hazard ratio=1.59, 95% confidence interval: 1.07-2.37, P=0.02). CONCLUSION: Elevation of serum GGT levels is an indicator of aggressive tumor behaviors and a predictor of poor clinical outcomes. It may prove to be a useful biomarker for identifying ICC patients at high risk of early recurrence and unfavorable prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Elevation of serum γ-glutamyltransferase as a predictor of aggressive tumor behaviors and unfavorable prognosis in patients with intrahepatic cholangiocarcinoma: analysis of a large monocenter study OBJECTIVE: γ-Glutamyltransferase (GGT) has been used as a diagnostic biomarker for hepatobiliary disease. However, little is known about its role in intrahepatic cholangiocarcinoma (ICC). The aim of the present study was to validate the clinical significance of GGT in predicting the prognosis of ICC patients. MATERIALS AND METHODS: A total of 411 patients with pathologically confirmed ICC were retrospectively analyzed. Of them, 307 patients underwent hepatectomy, 64 patients with unresectable tumors were treated with chemotherapy (n=42) or transcatheter arterial chemoembolization (n=22), and 40 patients with end-stage disease received supportive treatment. The association between GGT and the clinicopathological features and prognosis was assessed. RESULTS: Serum GGT levels were significantly associated with hepatitis B infection (P=0.02), the Child-Pugh grade (P=0.02), vascular invasion (P<0.001), lymph node involvement (P=0.04), and incomplete tumor encapsulation (P=0.009). Survival analysis showed that GGT was an independent predictor of a poor prognosis (hazard ratio=2.36, 95% confidence interval: 1.67-3.34, P=0.001). This prognostic value of GGT was further validated in the mass-forming, normal bilirubin, and Child-Pugh A subgroups. Subsequent recurrence analysis showed that a recurrence-free survival in patients with high GGT levels was significantly shorter than that in those with low GGT levels (6 vs. 12 months, P<0.001). The serum GGT level was an independent predictor of tumor recurrence in ICC patients (hazard ratio=1.59, 95% confidence interval: 1.07-2.37, P=0.02). CONCLUSION: Elevation of serum GGT levels is an indicator of aggressive tumor behaviors and a predictor of poor clinical outcomes. It may prove to be a useful biomarker for identifying ICC patients at high risk of early recurrence and unfavorable prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"curative intent surgery hilar cholangiocarcinoma prognostic factors clinical decision making background surgical approach hilar cholangiocarcinoma hc largely evolved increased resectability rates reported large series patients resections hc published last years potential predictors survival explored however usefulness predictors clinical decision making controversial purpose aim present review explore main prognostic factors curative intent surgery hc emerged current literature furthermore impact predictors clinical decision making assessed conclusion aggressive surgical approach improved survival rates patients hc implies bile duct resection associated liver resection loco regional lymph node dissection ajcc staging system remains main tool assess prognosis resection hc margin negative resections absence lymph node metastases main prognostic factor curative intent surgery hc response chemotherapy also prognostic factor markers systemic inflammatory response might predict prognosis patients hc usefulness clinical decision making remains unclear pubmed","probabilities":0.9799733,"Title":"Curative-intent surgery for hilar cholangiocarcinoma: prognostic factors for clinical decision making","Abstract":"BACKGROUND: The surgical approach for hilar cholangiocarcinoma (HC) has largely evolved, and increased resectability rates are reported. Large series of patients with resections for HC were published in the last years, and potential predictors for survival were explored. However, the usefulness of these predictors in clinical decision making is controversial. PURPOSE: The aim of the present review is to explore the main prognostic factors after curative-intent surgery for HC, as emerged from the current literature. Furthermore, the impact of these predictors on clinical decision making is assessed. CONCLUSION: An aggressive surgical approach has improved the survival rates in patients with HC and implies bile duct resection associated with liver resection and loco-regional lymph node dissection. The AJCC staging system remains the main tool to assess the prognosis after resection of HC. Margin-negative resections and absence of lymph node metastases are the main prognostic factor after curative-intent surgery for HC. Response to chemotherapy is also a prognostic factor. Markers of systemic inflammatory response might predict prognosis of patients with HC, but their usefulness in clinical decision making remains unclear.","Source":"PubMed","category":"HUMAN","training_data":"Curative-intent surgery for hilar cholangiocarcinoma: prognostic factors for clinical decision making BACKGROUND: The surgical approach for hilar cholangiocarcinoma (HC) has largely evolved, and increased resectability rates are reported. Large series of patients with resections for HC were published in the last years, and potential predictors for survival were explored. However, the usefulness of these predictors in clinical decision making is controversial. PURPOSE: The aim of the present review is to explore the main prognostic factors after curative-intent surgery for HC, as emerged from the current literature. Furthermore, the impact of these predictors on clinical decision making is assessed. CONCLUSION: An aggressive surgical approach has improved the survival rates in patients with HC and implies bile duct resection associated with liver resection and loco-regional lymph node dissection. The AJCC staging system remains the main tool to assess the prognosis after resection of HC. Margin-negative resections and absence of lymph node metastases are the main prognostic factor after curative-intent surgery for HC. Response to chemotherapy is also a prognostic factor. Markers of systemic inflammatory response might predict prognosis of patients with HC, but their usefulness in clinical decision making remains unclear. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological factors associated prognosis patients resectable perihilar cholangiocarcinoma systematic review meta analysis refinement surgical techniques combined preoperative management improved resectability rate perihilar cholangiocarcinoma pcca however prognosis pcca curative resection still dismal meta analysis performed investigate prognostic clinicopathological factors resectable pcca pubmed cochran library sciencedirect web science searched systematically identify reports focusing studying prognostic clinicopathological factors resectable pcca hazard ratios hrs 95 confidence interval 95 ci identified studies using cox proportional hazard regression model extracted overall survival os disease specific survival dss disease free survival dfs analysis three prospective 35 retrospective cohort studies including 5681 resectable pcca included pooled analysis among 20 clinicopathological factors associated negative survival pcca 6 included quantitative analysis showed lymph node involvement associated reduced os hr 2 04 95 ci 2 10 2 62 dss hr 1 80 95 ci 1 39 2 34 dfs hr 4 38 95 ci 1 89 10 14 negative resection margin hr 2 04 95 ci 1 73 2 41 operative transfusion hr 1 82 95 ci 1 06 3 11 t3 t4 stage hr 2 04 95 ci 2 04 2 53 poor prognostic factors os poor moderate differentiation also adverse prognostic factor os hr 2 71 95 ci 1 80 4 07 dss hr 1 74 95 ci 1 25 2 44 overall median resectability rate 95ci r0 resection 95ci 5 year os 95ci eastern western countries 74 9 66 4 78 4 41 3 32 6 80 8 70 7 65 6 80 8 75 9 64 0 80 4 33 0 29 7 39 7 25 5 20 0 31 6 respectively negative resection margin lymph node involvement poor moderate differentiation grade identified negative predictor factors resectable pcca operative transfusion t3 t4 stage also associated reduced survival resectable pcca pubmed","probabilities":0.9799733,"Title":"The clinicopathological factors associated with prognosis of patients with resectable perihilar cholangiocarcinoma: A systematic review and meta-analysis","Abstract":"The refinement in surgical techniques combined with the preoperative management has improved the resectability rate of perihilar cholangiocarcinoma (pCCA). However, the prognosis of pCCA with curative resection is still dismal. This meta-analysis was performed to investigate the prognostic clinicopathological factors in resectable pCCA.PubMed, the Cochran Library, ScienceDirect, and Web of Science were searched systematically to identify reports focusing on studying the prognostic clinicopathological factors in resectable pCCA. The hazard ratios (HRs) and its 95% confidence interval (95%CI) from the identified studies using Cox proportional hazard regression model were extracted for overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) analysis.Three prospective and 35 retrospective cohort studies including 5681 resectable pCCA were included in the pooled analysis. Among more than 20 clinicopathological factors associated with negative survival of pCCA, only 6 were included in quantitative analysis which showed that lymph node involvement was associated with a reduced OS (HR = 2.04; 95%CI: 2.10-2.62), DSS (HR = 1.80; 95%CI: 1.39-2.34), DFS (HR = 4.38; 95%CI: 1.89-10.14), negative resection margin (HR = 2.04; 95%CI:1.73-2.41), operative transfusion (HR = 1.82; 95%CI: 1.06-3.11), and T3 or T4-stage (HR = 2.04; 95%CI: 2.04-2.53) were poor prognostic factors of OS, and poor or moderate differentiation was also an adverse prognostic factor of OS (HR = 2.71; 95%CI: 1.80-4.07) and DSS (HR = 1.74; 95%CI: 1.25-2.44). The overall median resectability rate (95CI%), R0 resection (95CI%), and 5-year OS (95CI%) in Eastern and Western countries were 74.9 (66.4-78.4) % and 41.3 (32.6-80.8) %, 70.7 (65.6-80.8) % and 75.9 (64.0-80.4) %, and 33.0 (29.7-39.7) % and 25.5 (20.0-31.6) %, respectively.Negative resection margin, lymph node involvement, poor or moderate differentiation grade was identified as the negative predictor factors of resectable pCCA. Operative transfusion and T3/T4 stage were also associated with a reduced survival of resectable pCCA.","Source":"PubMed","category":"HUMAN","training_data":"The clinicopathological factors associated with prognosis of patients with resectable perihilar cholangiocarcinoma: A systematic review and meta-analysis The refinement in surgical techniques combined with the preoperative management has improved the resectability rate of perihilar cholangiocarcinoma (pCCA). However, the prognosis of pCCA with curative resection is still dismal. This meta-analysis was performed to investigate the prognostic clinicopathological factors in resectable pCCA.PubMed, the Cochran Library, ScienceDirect, and Web of Science were searched systematically to identify reports focusing on studying the prognostic clinicopathological factors in resectable pCCA. The hazard ratios (HRs) and its 95% confidence interval (95%CI) from the identified studies using Cox proportional hazard regression model were extracted for overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) analysis.Three prospective and 35 retrospective cohort studies including 5681 resectable pCCA were included in the pooled analysis. Among more than 20 clinicopathological factors associated with negative survival of pCCA, only 6 were included in quantitative analysis which showed that lymph node involvement was associated with a reduced OS (HR = 2.04; 95%CI: 2.10-2.62), DSS (HR = 1.80; 95%CI: 1.39-2.34), DFS (HR = 4.38; 95%CI: 1.89-10.14), negative resection margin (HR = 2.04; 95%CI:1.73-2.41), operative transfusion (HR = 1.82; 95%CI: 1.06-3.11), and T3 or T4-stage (HR = 2.04; 95%CI: 2.04-2.53) were poor prognostic factors of OS, and poor or moderate differentiation was also an adverse prognostic factor of OS (HR = 2.71; 95%CI: 1.80-4.07) and DSS (HR = 1.74; 95%CI: 1.25-2.44). The overall median resectability rate (95CI%), R0 resection (95CI%), and 5-year OS (95CI%) in Eastern and Western countries were 74.9 (66.4-78.4) % and 41.3 (32.6-80.8) %, 70.7 (65.6-80.8) % and 75.9 (64.0-80.4) %, and 33.0 (29.7-39.7) % and 25.5 (20.0-31.6) %, respectively.Negative resection margin, lymph node involvement, poor or moderate differentiation grade was identified as the negative predictor factors of resectable pCCA. Operative transfusion and T3/T4 stage were also associated with a reduced survival of resectable pCCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"proximal resection margins prognostic distal resection margins patients undergoing hilar cholangiocarcinoma resection purpose even though therapeutic gold standard hilar cholangiocarcinoma hcca resection cancer free resection margin rm surgical treatment still remains challenging study evaluated prognostic significance rm status resected hcca patients identified survival prognostic factors materials methods reviewed records 96 hcca patients underwent surgery 2001 2012 analyzed rm status prognostic factors affecting survival results negative rm n 31 33 significantly associated better survival vs positive rm n 65 67 mean survival time mst 33 months vs 21 months p 0 011 margins histological findings non dysplastic epithelium low grade dysplasia carcinoma situ associated survival differences mst 33 months vs 33 months vs 30 months p 0 452 whereas positive margins associated poorer survival relative carcinoma situ mst 30 months vs 21 months p 0 050 among patients r0 resection narrow 5 mm wide 5 mm margins associated survival differences mst 33 months vs 30 months p 0 234 although positive proximal rm associated poorer survival compared negative rm mst 19 vs 33 p 0 002 survival difference observed positive negative distal rms mst 30 vs 33 p 0 628 proximal rm positivity hazard ratio hr 2 688 p 0 007 nodal involvement hr 3 293 p 0 001 independent survival prognostic factors conclusion clear rm especially proximal rm status significant prognosticator proximal bile duct resection greatest technically feasible extent may necessary careful consideration potential morbidity oncologic outcomes resection however aggressive approach obtain negative distal rm might controversial considered carefully depending patient status pubmed","probabilities":0.9799733,"Title":"Proximal Resection Margins: More Prognostic than Distal Resection Margins in Patients Undergoing Hilar Cholangiocarcinoma Resection","Abstract":"PURPOSE: Even though the therapeutic gold standard of hilar cholangiocarcinoma (HCCA) resection is cancer-free resection margin (RM), surgical treatment still remains challenging. This study evaluated the prognostic significance of RM status in resected HCCA patients and identified survival prognostic factors. MATERIALS AND METHODS: We reviewed records of 96 HCCA patients who underwent surgery from 2001 to 2012 and analyzed the RM status and prognostic factors that affecting survival. RESULTS: Negative RM (n=31, 33%) was significantly associated with better survival vs. positive RM (n=65, 67%) (mean survival time [MST], 33 months vs. 21 months; p=0.011). Margins with histological findings of non-dysplastic epithelium, low-grade dysplasia, and carcinoma in situ were not associated with survival differences (MST, 33 months vs. 33 months vs. 30 months; p=0.452), whereas positive margins were associated with poorer survival relative to carcinoma in situ (MST, 30 months vs. 21 months; p=0.050). Among patients with R0 resection, narrow (≤ 5 mm) and wide (> 5 mm) margins were not associated with survival differences (MST, 33 months vs. 30 months; p=0.234). Although positive proximal RM was associated with poorer survival compared to negative RM (MST, 19 vs. 33; p=0.002), no survival difference was observed between positive and negative distal RMs (MST, 30 vs. 33; p=0.628). Proximal RM positivity (hazard ratio [HR], 2.688; p=0.007) and nodal involvement (HR, 3.293; p < 0.001) were independent survival prognostic factors. CONCLUSION: A clear RM, especially proximal RM status, was significant prognosticator, and proximal bile duct resection to the greatest technically feasible extent may be necessary, with careful consideration of the potential morbidity and oncologic outcomes after resection. However, an aggressive approach to obtain a negative distal RM might be controversial and should be considered carefully, depending on the patient's status.","Source":"PubMed","category":"HUMAN","training_data":"Proximal Resection Margins: More Prognostic than Distal Resection Margins in Patients Undergoing Hilar Cholangiocarcinoma Resection PURPOSE: Even though the therapeutic gold standard of hilar cholangiocarcinoma (HCCA) resection is cancer-free resection margin (RM), surgical treatment still remains challenging. This study evaluated the prognostic significance of RM status in resected HCCA patients and identified survival prognostic factors. MATERIALS AND METHODS: We reviewed records of 96 HCCA patients who underwent surgery from 2001 to 2012 and analyzed the RM status and prognostic factors that affecting survival. RESULTS: Negative RM (n=31, 33%) was significantly associated with better survival vs. positive RM (n=65, 67%) (mean survival time [MST], 33 months vs. 21 months; p=0.011). Margins with histological findings of non-dysplastic epithelium, low-grade dysplasia, and carcinoma in situ were not associated with survival differences (MST, 33 months vs. 33 months vs. 30 months; p=0.452), whereas positive margins were associated with poorer survival relative to carcinoma in situ (MST, 30 months vs. 21 months; p=0.050). Among patients with R0 resection, narrow (≤ 5 mm) and wide (> 5 mm) margins were not associated with survival differences (MST, 33 months vs. 30 months; p=0.234). Although positive proximal RM was associated with poorer survival compared to negative RM (MST, 19 vs. 33; p=0.002), no survival difference was observed between positive and negative distal RMs (MST, 30 vs. 33; p=0.628). Proximal RM positivity (hazard ratio [HR], 2.688; p=0.007) and nodal involvement (HR, 3.293; p < 0.001) were independent survival prognostic factors. CONCLUSION: A clear RM, especially proximal RM status, was significant prognosticator, and proximal bile duct resection to the greatest technically feasible extent may be necessary, with careful consideration of the potential morbidity and oncologic outcomes after resection. However, an aggressive approach to obtain a negative distal RM might be controversial and should be considered carefully, depending on the patient's status. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiology gallbladder polyps histological assessment cholecystectomy introduction gallbladder polyps divided neoplastic polyps adenoma dysplastic polyp carcinoma nonneoplastic polyps eg cholesterol polyp inflammatory polyp adenomyoma 1 cholecystectomy indicated neoplastic polyps pre malignant 2 annually 23 000 cholecystectomies performed netherlands 3 however scarce pathology data prevalence gallbladder polyps attribution neoplastic nonneoplastic polyps aims methods aimed assess nationwide pathology data gallbladder polyps 10 year period methods palga database dutch pathology registry 4 used identify histopathologically proven gallbladder polyps period 2003 2013 search restricted histological samples patients 18 years age biopsies cholecystectomies performed part primary non gallbladder surgery e g whipple hepatectomy excluded excerpts concerning primary gallbladder surgery containing polyp focal wall thickening 4 5 mm included excerpts rated neoplastic adenoma dysplasia carcinoma malignancies nonneoplastic types polyp neoplastic nonneoplastic lesions present excerpt classified neoplastic prevalence gallbladder polyps attribution neoplastic polyps nonneoplastic polyps calculated determine prevalence gallbladder polyps obtained total number cholecystectomies 2003 2013 palga results total 220 612 cholecystectomies performed period 2003 2013 palga search identified 4532 excerpts representing 4349 patients total 337 patients excluded due primary non gallbladder surgery leaving 4012 unique cholecystectomies 2083 cholecystectomies 0 9 polypoid leasion present results calculated prevalence polyps 944 100 000 patients undergone cholecystectomy polyps 1172 56 3 neoplastic 278 13 3 adenomas incl cystadenoma 190 9 1 dysplastic polyps 647 31 1 adenocarcinomas 57 2 7 malignancies nine hundred ten 43 7 polyp nonneoplastic 375 18 cholesterol polyps 334 16 adenomyoma 70 3 7 hyperplastic polyps 54 2 6 mucosal polyps 42 2 0 inflammatory polyps 18 0 9 papiloma 17 0 8 types polyps conclusion approximately one percent gallbladders contain polyp histopathological assessment cholecystectomy fifty six percent polyps cholecystectomy neoplastic disclosure interest authors declared conflicts interest google scholar","probabilities":0.9799733,"Title":"Epidemiology Of Gallbladder Polyps On Histological Assessment After Cholecystectomy","Abstract":"Introduction: Gallbladder polyps can be divided in neoplastic polyps (adenoma, dysplastic polyp, and carcinoma) and nonneoplastic polyps (eg. cholesterol polyp, inflammatory polyp or adenomyoma).1 Cholecystectomy is only indicated for neoplastic polyps, as they are (pre)malignant.2 Annually, over 23,000 cholecystectomies are performed in the Netherlands.3 However, there is scarce pathology data on the prevalence of gallbladder polyps and attribution of neoplastic and nonneoplastic polyps. Aims & Methods: We aimed to assess nationwide pathology data on gallbladder polyps over a 10-year period. Methods: The PALGA database, the Dutch Pathology Registry,4 was used to identify all histopathologically proven gallbladder polyps over the period 2003–2013. The search was restricted to histological samples of patients\u000418 years of age. Biopsies, and cholecystectomies performed as part of primary non-gallbladder surgery (e.g. whipple or hepatectomy), were excluded. All excerpts concerning primary gallbladder surgery containing a polyp or (focal) wall thickening 4 5 mm were included. These excerpts were rated as neoplastic (adenoma, dysplasia, carcinoma or other malignancies) or nonneoplastic (all other types of polyp). If both neoplastic and nonneoplastic lesions were present, the excerpt was classified as neoplastic. Prevalence of gallbladder polyps and the attribution of neoplastic polyps and nonneoplastic polyps was calculated. To determine prevalence of gallbladder polyps, we obtained the total number of cholecystectomies between 2003–2013 from PALGA. Results: In total 220,612 cholecystectomies were performed over the period 2003– 2013. The PALGA search identified 4532 excerpts, representing 4349 patients. A total of 337 patients were excluded due to primary non-gallbladder surgery, leaving 4012 unique cholecystectomies. In 2083 cholecystectomies (0.9%), a polypoid leasion was present. Which results in a calculated prevalence of polyps in 944/100,000 patients who undergone cholecystectomy. Of the polyps, 1172 (56.3%) were neoplastic; 278 (13.3%) adenomas (incl. cystadenoma), 190 (9.1%) dysplastic polyps, 647 (31.1%) adenocarcinomas, and 57 (2.7%) other malignancies. Nine hundred and ten (43.7%) polyp were nonneoplastic; 375 (18%) cholesterol polyps, 334 (16%) adenomyoma’s, 70 (3.7%) hyperplastic polyps, 54 (2.6%) mucosal polyps, 42 (2.0%) inflammatory polyps, 18 (0.9%) papiloma’s and 17 (0.8%) other types of polyps. Conclusion: Approximately one percent of gallbladders contain a polyp on histopathological assessment after cholecystectomy. Fifty-six percent of the polyps after cholecystectomy are neoplastic. Disclosure of Interest: All authors have declared no conflicts of interest","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology Of Gallbladder Polyps On Histological Assessment After Cholecystectomy Introduction: Gallbladder polyps can be divided in neoplastic polyps (adenoma, dysplastic polyp, and carcinoma) and nonneoplastic polyps (eg. cholesterol polyp, inflammatory polyp or adenomyoma).1 Cholecystectomy is only indicated for neoplastic polyps, as they are (pre)malignant.2 Annually, over 23,000 cholecystectomies are performed in the Netherlands.3 However, there is scarce pathology data on the prevalence of gallbladder polyps and attribution of neoplastic and nonneoplastic polyps. Aims & Methods: We aimed to assess nationwide pathology data on gallbladder polyps over a 10-year period. Methods: The PALGA database, the Dutch Pathology Registry,4 was used to identify all histopathologically proven gallbladder polyps over the period 2003–2013. The search was restricted to histological samples of patients\u000418 years of age. Biopsies, and cholecystectomies performed as part of primary non-gallbladder surgery (e.g. whipple or hepatectomy), were excluded. All excerpts concerning primary gallbladder surgery containing a polyp or (focal) wall thickening 4 5 mm were included. These excerpts were rated as neoplastic (adenoma, dysplasia, carcinoma or other malignancies) or nonneoplastic (all other types of polyp). If both neoplastic and nonneoplastic lesions were present, the excerpt was classified as neoplastic. Prevalence of gallbladder polyps and the attribution of neoplastic polyps and nonneoplastic polyps was calculated. To determine prevalence of gallbladder polyps, we obtained the total number of cholecystectomies between 2003–2013 from PALGA. Results: In total 220,612 cholecystectomies were performed over the period 2003– 2013. The PALGA search identified 4532 excerpts, representing 4349 patients. A total of 337 patients were excluded due to primary non-gallbladder surgery, leaving 4012 unique cholecystectomies. In 2083 cholecystectomies (0.9%), a polypoid leasion was present. Which results in a calculated prevalence of polyps in 944/100,000 patients who undergone cholecystectomy. Of the polyps, 1172 (56.3%) were neoplastic; 278 (13.3%) adenomas (incl. cystadenoma), 190 (9.1%) dysplastic polyps, 647 (31.1%) adenocarcinomas, and 57 (2.7%) other malignancies. Nine hundred and ten (43.7%) polyp were nonneoplastic; 375 (18%) cholesterol polyps, 334 (16%) adenomyoma’s, 70 (3.7%) hyperplastic polyps, 54 (2.6%) mucosal polyps, 42 (2.0%) inflammatory polyps, 18 (0.9%) papiloma’s and 17 (0.8%) other types of polyps. Conclusion: Approximately one percent of gallbladders contain a polyp on histopathological assessment after cholecystectomy. Fifty-six percent of the polyps after cholecystectomy are neoplastic. Disclosure of Interest: All authors have declared no conflicts of interest Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"systemic therapy younger elderly patients advanced biliary cancer sub analysis abc 02 twelve prospective trials background outcomes younger 40 years elderly 70 years patients advanced biliary cancer abc receiving palliative chemotherapy unclear study assessed outcomes receiving monotherapy combination therapy thirteen prospective systemic therapy trials methods multivariable analysis explored impact therapy progression free pfs overall survival os two separate age cohort groups 70 years 70 years 40 years 40 years results overall 1163 patients recruited jan 1997 dec 2013 median age entire cohort 63 years range 23 85 36 3 40 260 22 70 combination therapy platinum based nine studies among patients 40 70 years 23 64 182 70 received combination therapy respectively median follow 42 months 95 ci 37 51 median pfs patients 40 40 years 3 5 5 9 months p 0 12 os 10 8 9 7 months respectively p 0 55 median pfs 70 70 years 6 0 5 0 months p 0 53 os 10 2 8 8 months respectively p 0 08 entire cohort pfs os significantly better receiving combination therapy hazard ratio hr 0 66 95 ci 0 58 0 76 p 0 0001 hr 0 72 95 ci 0 63 0 82 p 0 0001 respectively patients 70 years hr 0 54 95 ci 0 38 0 77 p 0 001 hr 0 60 95 ci 0 43 0 85 p 0 004 respectively evidence interaction age treatment pfs p 0 58 p 0 66 os p 0 18 p 0 75 conclusions abc younger patients rare survival elderly patients receipt systemic therapy advanced disease whether monotherapy combination therapy similar non elderly patients therefore age alone influence decisions regarding treatment pubmed","probabilities":0.9799733,"Title":"Systemic therapy in younger and elderly patients with advanced biliary cancer: sub-analysis of ABC-02 and twelve other prospective trials","Abstract":"BACKGROUND: Outcomes in younger (<40 years) and elderly (≥70 years) patients with advanced biliary cancer (ABC) receiving palliative chemotherapy are unclear. This study assessed outcomes in those receiving monotherapy or combination therapy in thirteen prospective systemic-therapy trials. METHODS: Multivariable analysis explored the impact of therapy on progression-free (PFS) and overall survival (OS) in two separate age cohort groups: <70 years and ≥70 years, and <40 years and ≥40 years. RESULTS: Overall, 1163 patients were recruited (Jan 1997-Dec 2013). Median age of entire cohort: 63 years (range 23-85); 36 (3%) were <40, 260 (22%); ≥70. Combination therapy was platinum-based in nine studies. Among patients <40 and ≥70 years, 23 (64%) and 182 (70%) received combination therapy, respectively. Median follow-up was 42 months (95%-CI 37-51). Median PFS for patients <40 and ≥40 years was 3.5 and 5.9 months (P = 0.12), and OS was 10.8 and 9.7 months, respectively (P = 0.55). Median PFS for those <70 and ≥70 years was 6.0 and 5.0 months (P = 0.53), and OS was 10.2 and 8.8 months, respectively (P = 0.08). For the entire cohort, PFS and OS were significantly better in those receiving combination therapy: Hazard Ratio [HR]-0.66, 95%-CI 0.58-0.76, P < 0.0001 and HR-0.72, 95%-CI 0.63-0.82, P < 0.0001, respectively; and in patients ≥70 years: HR-0.54 (95%-CI 0.38-0.77, P = 0.001) and HR-0.60 (95%-CI 0.43-0.85, P = 0.004), respectively. There was no evidence of interaction between age and treatment for PFS (P = 0.58, P = 0.66) or OS (P = 0.18, P = 0.75). CONCLUSIONS: In ABC, younger patients are rare, and survival in elderly patients in receipt of systemic therapy for advanced disease, whether monotherapy or combination therapy, is similar to that of non-elderly patients, therefore age alone should not influence decisions regarding treatment.","Source":"PubMed","category":"HUMAN","training_data":"Systemic therapy in younger and elderly patients with advanced biliary cancer: sub-analysis of ABC-02 and twelve other prospective trials BACKGROUND: Outcomes in younger (<40 years) and elderly (≥70 years) patients with advanced biliary cancer (ABC) receiving palliative chemotherapy are unclear. This study assessed outcomes in those receiving monotherapy or combination therapy in thirteen prospective systemic-therapy trials. METHODS: Multivariable analysis explored the impact of therapy on progression-free (PFS) and overall survival (OS) in two separate age cohort groups: <70 years and ≥70 years, and <40 years and ≥40 years. RESULTS: Overall, 1163 patients were recruited (Jan 1997-Dec 2013). Median age of entire cohort: 63 years (range 23-85); 36 (3%) were <40, 260 (22%); ≥70. Combination therapy was platinum-based in nine studies. Among patients <40 and ≥70 years, 23 (64%) and 182 (70%) received combination therapy, respectively. Median follow-up was 42 months (95%-CI 37-51). Median PFS for patients <40 and ≥40 years was 3.5 and 5.9 months (P = 0.12), and OS was 10.8 and 9.7 months, respectively (P = 0.55). Median PFS for those <70 and ≥70 years was 6.0 and 5.0 months (P = 0.53), and OS was 10.2 and 8.8 months, respectively (P = 0.08). For the entire cohort, PFS and OS were significantly better in those receiving combination therapy: Hazard Ratio [HR]-0.66, 95%-CI 0.58-0.76, P < 0.0001 and HR-0.72, 95%-CI 0.63-0.82, P < 0.0001, respectively; and in patients ≥70 years: HR-0.54 (95%-CI 0.38-0.77, P = 0.001) and HR-0.60 (95%-CI 0.43-0.85, P = 0.004), respectively. There was no evidence of interaction between age and treatment for PFS (P = 0.58, P = 0.66) or OS (P = 0.18, P = 0.75). CONCLUSIONS: In ABC, younger patients are rare, and survival in elderly patients in receipt of systemic therapy for advanced disease, whether monotherapy or combination therapy, is similar to that of non-elderly patients, therefore age alone should not influence decisions regarding treatment. PubMed","prediction_labels":"HUMAN"},{"cleaned":"intrahepatic cholangiocarcinoma new insights pathology cholangiocarcinomas malignant tumors derive cholangiocytes small intrahepatic bile ducts bile ductules intrahepatic cholangiocarcinoma icc large hilar extrahepatic bile ducts extrahepatic cholangiocarcinoma ecc icc ecc differ morphology pathogenesis risk factors treatment prognosis review focuses icc rising incidence emergence hepatitis c virus hcv infection risk factor authors examined 73 icc resected mount sinai medical center new york city reviewed literature tumors categorized classical nonclassical iccs based histopathology classical iccs 54 8 characterized tubular glandular nested pattern growth significantly associated tumor size 5 cm absence underlying liver disease advanced fibrosis nonclassical iccs 45 2 consisted tumors trabecular architecture tumors exhibited features extrahepatic carcinomas carcinomas considered derived hepatic progenitor cells e combined hepatocellular cholangiocarcinomas cholangiolocellular carcinomas ductular type icc smaller often arose chronic liver disease mostly hcv infection significant fibrosis role immunohistochemistry diagnosis icc importance new american joint committee cancer staging system icc also discussed pubmed","probabilities":0.9799733,"Title":"Intrahepatic cholangiocarcinoma: new insights in pathology","Abstract":"Cholangiocarcinomas are malignant tumors that derive from cholangiocytes of small intrahepatic bile ducts or bile ductules (intrahepatic cholangiocarcinoma; ICC), or of large hilar or extrahepatic bile ducts (extrahepatic cholangiocarcinoma; ECC). ICC and ECC differ in morphology, pathogenesis, risk factors, treatment, and prognosis. This review focuses on ICC, which is rising in incidence with the emergence of hepatitis C virus (HCV) infection as a risk factor. The authors examined 73 ICC, which were resected at The Mount Sinai Medical Center in New York City, and reviewed the literature. The tumors were categorized into classical and nonclassical ICCs based on histopathology. Classical ICCs (54.8%) were characterized by a tubular, glandular, or nested pattern of growth, were significantly associated with tumor size of more than 5 cm and the absence of underlying liver disease and/or advanced fibrosis. Nonclassical ICCs (45.2%) consisted of tumors with trabecular architecture, tumors that exhibited features of extrahepatic carcinomas, and carcinomas considered to be derived from hepatic progenitor cells, i.e., combined hepatocellular/cholangiocarcinomas and cholangiolocellular carcinomas (ductular type of ICC). They were smaller and often arose in chronic liver disease, mostly HCV infection, and/or with significant fibrosis. The role of immunohistochemistry in the diagnosis of ICC and the importance of the new American Joint Committee on Cancer Staging System for ICC are also discussed.","Source":"PubMed","category":"HUMAN","training_data":"Intrahepatic cholangiocarcinoma: new insights in pathology Cholangiocarcinomas are malignant tumors that derive from cholangiocytes of small intrahepatic bile ducts or bile ductules (intrahepatic cholangiocarcinoma; ICC), or of large hilar or extrahepatic bile ducts (extrahepatic cholangiocarcinoma; ECC). ICC and ECC differ in morphology, pathogenesis, risk factors, treatment, and prognosis. This review focuses on ICC, which is rising in incidence with the emergence of hepatitis C virus (HCV) infection as a risk factor. The authors examined 73 ICC, which were resected at The Mount Sinai Medical Center in New York City, and reviewed the literature. The tumors were categorized into classical and nonclassical ICCs based on histopathology. Classical ICCs (54.8%) were characterized by a tubular, glandular, or nested pattern of growth, were significantly associated with tumor size of more than 5 cm and the absence of underlying liver disease and/or advanced fibrosis. Nonclassical ICCs (45.2%) consisted of tumors with trabecular architecture, tumors that exhibited features of extrahepatic carcinomas, and carcinomas considered to be derived from hepatic progenitor cells, i.e., combined hepatocellular/cholangiocarcinomas and cholangiolocellular carcinomas (ductular type of ICC). They were smaller and often arose in chronic liver disease, mostly HCV infection, and/or with significant fibrosis. The role of immunohistochemistry in the diagnosis of ICC and the importance of the new American Joint Committee on Cancer Staging System for ICC are also discussed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ablative radiation therapy doses lead substantial prolongation survival patients inoperable intrahepatic cholangiocarcinoma purpose standard therapies localized inoperable intrahepatic cholangiocarcinoma ihcc ineffective advances radiotherapy rt techniques image guidance enabled ablative doses delivered large liver tumors study evaluated effects rt dose escalation treatment ihcc patients methods seventy nine consecutive patients inoperable ihcc identified treated definitive rt 2002 2014 diagnosis median tumor size 7 9 cm range 2 2 17 cm seventy patients 89 received systemic chemotherapy rt rt doses 35 100 gy median 58 05 gy three 30 fractions median biologic equivalent dose bed 80 5 gy range 43 75 180 gy results median follow time patients alive time analysis 33 months range 11 93 months median overall survival os time diagnosis 30 months 3 year os rate 44 radiation dose single important prognostic factor higher doses correlated improved local control lc rate os 3 year os rate patients receiving bed greater 80 5 gy 73 versus 38 receiving lower doses p 017 3 year lc rate significantly higher 78 bed greater 80 5 gy lower doses 45 p 04 bed continuous variable significantly affected lc p 009 os p 004 significant treatment related toxicities conclusion delivery higher doses rt improves lc os inoperable ihcc bed greater 80 5 gy seems ablative dose rt large ihccs long term survival rates compare favorably resection stn","probabilities":0.9799733,"Title":"Ablative Radiation Therapy Doses Lead To A Substantial Prolongation Of Survival In Patients With Inoperable Intrahepatic Cholangiocarcinoma","Abstract":"Purpose: Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. \r\n\r\n Patients and methods: Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). \r\n\r\n Results: Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. \r\n\r\n Conclusion: Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection.","Source":"STN","category":"HUMAN","training_data":"Ablative Radiation Therapy Doses Lead To A Substantial Prolongation Of Survival In Patients With Inoperable Intrahepatic Cholangiocarcinoma Purpose: Standard therapies for localized inoperable intrahepatic cholangiocarcinoma (IHCC) are ineffective. Advances in radiotherapy (RT) techniques and image guidance have enabled ablative doses to be delivered to large liver tumors. This study evaluated the effects of RT dose escalation in the treatment of IHCC. \r\n\r\n Patients and methods: Seventy-nine consecutive patients with inoperable IHCC were identified and treated with definitive RT from 2002 to 2014. At diagnosis, the median tumor size was 7.9 cm (range, 2.2 to 17 cm). Seventy patients (89%) received systemic chemotherapy before RT. RT doses were 35 to 100 Gy (median, 58.05 Gy) in three to 30 fractions for a median biologic equivalent dose (BED) of 80.5 Gy (range, 43.75 to 180 Gy). \r\n\r\n Results: Median follow-up time for patients alive at time of analysis was 33 months (range, 11 to 93 months). Median overall survival (OS) time after diagnosis was 30 months; 3-year OS rate was 44%. Radiation dose was the single most important prognostic factor; higher doses correlated with an improved local control (LC) rate and OS. The 3-year OS rate for patients receiving BED greater than 80.5 Gy was 73% versus 38% for those receiving lower doses (P = .017); 3-year LC rate was significantly higher (78%) after a BED greater than 80.5 Gy than after lower doses (45%, P = .04). BED as a continuous variable significantly affected LC (P = .009) and OS (P = .004). There were no significant treatment-related toxicities. \r\n\r\n Conclusion: Delivery of higher doses of RT improves LC and OS in inoperable IHCC. A BED greater than 80.5 Gy seems to be an ablative dose of RT for large IHCCs, with long-term survival rates that compare favorably with resection. STN","prediction_labels":"HUMAN"},{"cleaned":"hepatobiliary pancreatic neoplasms patients mccune albright syndrome background mccune albright syndrome mas includes polycystic fibrous dysplasia precocious puberty caf au lait spots rare disorder caused somatic activating mutations gnas gene gnas mutations also implicated various sporadic tumors including hepatobiliary pancreatic neoplasms aim aim study assess prevalence hepatobiliary pancreatic neoplasms patients mccune albright syndrome patients methods nineteen patients diagnosed 1995 2012 mas tertiary referral center rare growth disorders screened dedicated gadolinium enhanced magnetic resonance imaging hepatobiliary pancreatic neoplasms june 2011 december 2012 results six 32 19 screened patients found hepatic pancreatic biliary lesions excluding liver hemangiomas liver cysts focal nodular hyperplasia includes pancreatic ductal lesions observed 4 patients including numerous branch duct intraductal papillary mucinous neoplasms 3 patients biliary lesions observed 1 patient large choledochal cyst also involving left biliary branch finally multiple inflammatory telangiectatic hepatic adenomas observed 2 patients including 1 proven somatic gnas mutation conclusion describe first observation syndromic intraductal papillary mucinous neoplasms new association mas pancreatic neoplasms namely intraductal papillary mucinous neoplasms pancreas also rare hepatobiliary neoplasms including liver adenomas choledochal cysts findings strongly suggest somatic activating gnas mutations possibly camp pathway disorders involved tumorigenesis hepatobiliary pancreatic tissues originating foregut endoderm led us use routine screening dedicated magnetic resonance imaging including pancreatobiliary liver sequences patients mas google scholar","probabilities":0.9285714,"Title":"Hepatobiliary And Pancreatic Neoplasms In Patients With Mccune-Albright Syndrome","Abstract":"Background:\nMcCune-Albright syndrome (MAS), which includes polycystic fibrous dysplasia, precocious puberty, and café au lait spots, is a rare disorder caused by somatic activating mutations of the GNAS gene. GNAS mutations have also been implicated in various sporadic tumors, including hepatobiliary and pancreatic neoplasms.\nAim:\nThe aim of this study was to assess the prevalence of hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome.\nPatients and Methods:\nNineteen patients diagnosed between 1995 and 2012 with MAS in a tertiary referral center for rare growth disorders were screened with dedicated gadolinium-enhanced magnetic resonance imaging for hepatobiliary and pancreatic neoplasms between June 2011 and December 2012.\nResults:\nSix (32%) of the 19 screened patients were found to have hepatic, pancreatic, or biliary lesions, excluding liver hemangiomas, liver cysts, and focal nodular hyperplasia. This includes pancreatic ductal lesions observed in 4 patients, including numerous branch-duct intraductal papillary mucinous neoplasms in 3 patients. Biliary lesions were observed in 1 patient, with a large choledochal cyst also involving the left biliary branch. Finally, multiple inflammatory/telangiectatic hepatic adenomas were observed in 2 patients, including 1 with proven somatic GNAS mutation.\nConclusion:\nWe describe the first observation of syndromic intraductal papillary mucinous neoplasms and the new association between MAS and pancreatic neoplasms, namely intraductal papillary mucinous neoplasms of the pancreas but also rare hepatobiliary neoplasms including liver adenomas and choledochal cysts. These findings strongly suggest that somatic activating GNAS mutations, possibly through cAMP pathway disorders, are involved in the tumorigenesis of hepatobiliary and pancreatic tissues originating from the foregut endoderm and have led us to use a routine screening by dedicated magnetic resonance imaging including both pancreatobiliary and liver sequences in patients with MAS.","Source":"Google Scholar","category":"HUMAN","training_data":"Hepatobiliary And Pancreatic Neoplasms In Patients With Mccune-Albright Syndrome Background:\nMcCune-Albright syndrome (MAS), which includes polycystic fibrous dysplasia, precocious puberty, and café au lait spots, is a rare disorder caused by somatic activating mutations of the GNAS gene. GNAS mutations have also been implicated in various sporadic tumors, including hepatobiliary and pancreatic neoplasms.\nAim:\nThe aim of this study was to assess the prevalence of hepatobiliary and pancreatic neoplasms in patients with McCune-Albright syndrome.\nPatients and Methods:\nNineteen patients diagnosed between 1995 and 2012 with MAS in a tertiary referral center for rare growth disorders were screened with dedicated gadolinium-enhanced magnetic resonance imaging for hepatobiliary and pancreatic neoplasms between June 2011 and December 2012.\nResults:\nSix (32%) of the 19 screened patients were found to have hepatic, pancreatic, or biliary lesions, excluding liver hemangiomas, liver cysts, and focal nodular hyperplasia. This includes pancreatic ductal lesions observed in 4 patients, including numerous branch-duct intraductal papillary mucinous neoplasms in 3 patients. Biliary lesions were observed in 1 patient, with a large choledochal cyst also involving the left biliary branch. Finally, multiple inflammatory/telangiectatic hepatic adenomas were observed in 2 patients, including 1 with proven somatic GNAS mutation.\nConclusion:\nWe describe the first observation of syndromic intraductal papillary mucinous neoplasms and the new association between MAS and pancreatic neoplasms, namely intraductal papillary mucinous neoplasms of the pancreas but also rare hepatobiliary neoplasms including liver adenomas and choledochal cysts. These findings strongly suggest that somatic activating GNAS mutations, possibly through cAMP pathway disorders, are involved in the tumorigenesis of hepatobiliary and pancreatic tissues originating from the foregut endoderm and have led us to use a routine screening by dedicated magnetic resonance imaging including both pancreatobiliary and liver sequences in patients with MAS. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"primary revision efficacy cross wired metallic stents endoscopic bilateral stent stent placement malignant hilar biliary strictures background study aims endoscopic bilateral drainage inoperable malignant hilar biliary strictures hbs using metal stents considered technically difficult furthermore endoscopic revision bilateral stenting occlusion challenging study performed evaluate long term efficacy endoscopic bilateral stent stent placement cross wired metallic stents high grade malignant hbs planned endoscopic bilateral revision patients methods total 84 patients inoperable high grade malignant hbs enrolled three academic tertiary referral centers two cross wired metal stents inserted using bilateral stent stent placement method bilateral endoscopic revision also performed follow using either identical metal stents plastic stents main outcome measurements technical functional success complications stent patency endoscopic revision efficacy results technical clinical success rates endoscopic bilateral stent stent placement cross wired metallic stents 95 2 80 84 92 9 78 84 respectively median patency range survival 238 days 10 429 256 days 10 1130 respectively obstruction primary bilateral stents occurred 30 8 24 78 patients functionally successful stent placement technical clinical success rates planned bilateral endoscopic revision occluded stents 83 3 20 24 79 2 19 24 respectively revision bilateral metallic stents placed 11 patients 55 0 remaining patients received plastic stents conclusions palliative endoscopic bilateral stent stent placement cross wired metallic stents effective patients inoperable hbs revision endoscopic bilateral stenting may feasible successful cases primary deployed metal stents occluded pubmed","probabilities":0.9799733,"Title":"Primary and revision efficacy of cross-wired metallic stents for endoscopic bilateral stent-in-stent placement in malignant hilar biliary strictures","Abstract":"BACKGROUND AND STUDY AIMS: Endoscopic bilateral drainage for inoperable malignant hilar biliary strictures (HBS) using metal stents is considered to be technically difficult. Furthermore, endoscopic revision of bilateral stenting after occlusion can be challenging. This study was performed to evaluate the long-term efficacy of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents in high-grade malignant HBS and planned endoscopic bilateral revision. PATIENTS AND METHODS: A total of 84 patients with inoperable high-grade malignant HBS were enrolled from three academic tertiary referral centers. Two cross-wired metal stents were inserted using a bilateral stent-in-stent placement method. Bilateral endoscopic revision was also performed during follow-up using either identical metal stents or plastic stents. The main outcome measurements were technical and functional success, complications, stent patency, and endoscopic revision efficacy. RESULTS: The technical and clinical success rates of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents were 95.2% (80/84) and 92.9% (78/84), respectively. Median patency (range) and survival were 238 days (10-429) and 256 days (10-1130), respectively. Obstruction of primary bilateral stents occurred in 30.8% (24/78) of patients with functionally successful stent placement. The technical and clinical success rates of planned bilateral endoscopic revision for occluded stents were 83.3% (20/24) and 79.2% (19/24), respectively. For revision, bilateral metallic stents were placed in 11 patients (55.0%); the remaining patients received plastic stents. CONCLUSIONS: Palliative endoscopic bilateral stent-in-stent placement of cross-wired metallic stents was effective in patients with inoperable HBS. Revision endoscopic bilateral stenting may be feasible and successful in cases where the primary deployed metal stents are occluded.","Source":"PubMed","category":"HUMAN","training_data":"Primary and revision efficacy of cross-wired metallic stents for endoscopic bilateral stent-in-stent placement in malignant hilar biliary strictures BACKGROUND AND STUDY AIMS: Endoscopic bilateral drainage for inoperable malignant hilar biliary strictures (HBS) using metal stents is considered to be technically difficult. Furthermore, endoscopic revision of bilateral stenting after occlusion can be challenging. This study was performed to evaluate the long-term efficacy of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents in high-grade malignant HBS and planned endoscopic bilateral revision. PATIENTS AND METHODS: A total of 84 patients with inoperable high-grade malignant HBS were enrolled from three academic tertiary referral centers. Two cross-wired metal stents were inserted using a bilateral stent-in-stent placement method. Bilateral endoscopic revision was also performed during follow-up using either identical metal stents or plastic stents. The main outcome measurements were technical and functional success, complications, stent patency, and endoscopic revision efficacy. RESULTS: The technical and clinical success rates of endoscopic bilateral stent-in-stent placement of cross-wired metallic stents were 95.2% (80/84) and 92.9% (78/84), respectively. Median patency (range) and survival were 238 days (10-429) and 256 days (10-1130), respectively. Obstruction of primary bilateral stents occurred in 30.8% (24/78) of patients with functionally successful stent placement. The technical and clinical success rates of planned bilateral endoscopic revision for occluded stents were 83.3% (20/24) and 79.2% (19/24), respectively. For revision, bilateral metallic stents were placed in 11 patients (55.0%); the remaining patients received plastic stents. CONCLUSIONS: Palliative endoscopic bilateral stent-in-stent placement of cross-wired metallic stents was effective in patients with inoperable HBS. Revision endoscopic bilateral stenting may be feasible and successful in cases where the primary deployed metal stents are occluded. PubMed","prediction_labels":"HUMAN"},{"cleaned":"value thioredoxin family proteins proliferation markers dysplastic malignant gallbladders patients primary sclerosing cholangitis background aims patients primary sclerosing cholangitis psc increased risk biliary gallbladder malignancy markers early malignancy psc lacking aims evaluate biomarkers look premalignancy malignancy methods available gallbladder specimens n 53 patients psc karolinska university hospital 1985 2006 reviewed immunohistochemical staining p53 ki 67 cyclin d1 thioredoxin family redox proteins thioredoxin reductase 1 trxr1 isoform trxr1 v 2 3 5 thioredoxin trx1 glutaredoxin1 grx1 performed tissues patients carcinoma n 6 dysplasia n 7 non cancerous gallbladder epithelium n 6 results dysplasia carcinoma found 16 53 30 cases inflammation fibrosis gallbladder wall common tissue gallbladder dysplasia carcinoma benign tissue 12 25 48 versus 4 28 12 p 0 01 13 21 62 versus 3 32 9 p 0 0001 respectively immunoreactivity p53 ki67 cyclin d1 detected significantly cases dysplasia carcinoma gallbladder non cancerous epithelium 2 19 11 samples positive non cancerous epithelium versus 7 17 41 dysplasia carcinoma p 0 05 trxr1 v 2 3 5 grx1 regulated specifically 15 19 79 positive cases non cancerous epithelium versus 7 17 41 dysplasia carcinoma conclusion psc patients frequency gallbladder dysplasia carcinoma 30 operative specimens overexpression trxr1 v2 3 5 regulation grx1 dysplastic gallbladder epithelium suggest proteins evaluated possible future immunohistochemical markers early diagnosis biliary malignancy psc stn","probabilities":1.0,"Title":"The Value Of Thioredoxin Family Proteins And Proliferation Markers In Dysplastic And Malignant Gallbladders In Patients With Primary Sclerosing Cholangitis","Abstract":"Background and aims: Patients with primary sclerosing cholangitis (PSC) have an increased risk for biliary and gallbladder malignancy and markers of early malignancy in PSC are lacking. The aims were to evaluate biomarkers to look for premalignancy/malignancy. \n\n Methods: All available gallbladder specimens (n = 53) in patients with PSC at Karolinska University Hospital between 1985 and 2006 were reviewed. Immunohistochemical staining for p53, Ki-67, Cyclin D1 and the thioredoxin family redox proteins; Thioredoxin reductase 1 (TrxR1), isoform-TrxR1-v.2.3.5, Thioredoxin (Trx1) and Glutaredoxin1 (Grx1) was performed on tissues from patients with carcinoma (n = 6), dysplasia (n = 7) and non-cancerous gallbladder epithelium (n = 6). \n\n Results: Dysplasia and carcinoma were found in 16/53 (30%) cases. Inflammation and fibrosis of the gallbladder wall were more common in tissue with gallbladder dysplasia/carcinoma than in benign tissue 12/25 (48%) versus 4/28 (12%) (p < 0.01) and in 13/21 (62%) versus 3/32 (9%) (p < 0.0001), respectively. Immunoreactivity for p53, Ki67, Cyclin D1 was detected in significantly more cases of dysplasia/carcinoma of the gallbladder than in non-cancerous epithelium. 2/19 (11%) of the samples were positive in non-cancerous epithelium versus 7/17 (41%) in dysplasia/carcinoma (p < 0.05) for TrxR1-v.2.3.5. Grx1 was down regulated; more specifically 15/19 (79%) positive cases in non-cancerous epithelium versus 7/17 (41%) in dysplasia/carcinoma. \n\n Conclusion: PSC patients have a frequency of gallbladder dysplasia/carcinoma of 30% in operative specimens. The overexpression of TrxR1-v2,3,5 and down regulation of Grx1 in dysplastic gallbladder epithelium suggest that these proteins should be further evaluated as possible future immunohistochemical markers in the early diagnosis of biliary malignancy in PSC.","Source":"STN","category":"HUMAN","training_data":"The Value Of Thioredoxin Family Proteins And Proliferation Markers In Dysplastic And Malignant Gallbladders In Patients With Primary Sclerosing Cholangitis Background and aims: Patients with primary sclerosing cholangitis (PSC) have an increased risk for biliary and gallbladder malignancy and markers of early malignancy in PSC are lacking. The aims were to evaluate biomarkers to look for premalignancy/malignancy. \n\n Methods: All available gallbladder specimens (n = 53) in patients with PSC at Karolinska University Hospital between 1985 and 2006 were reviewed. Immunohistochemical staining for p53, Ki-67, Cyclin D1 and the thioredoxin family redox proteins; Thioredoxin reductase 1 (TrxR1), isoform-TrxR1-v.2.3.5, Thioredoxin (Trx1) and Glutaredoxin1 (Grx1) was performed on tissues from patients with carcinoma (n = 6), dysplasia (n = 7) and non-cancerous gallbladder epithelium (n = 6). \n\n Results: Dysplasia and carcinoma were found in 16/53 (30%) cases. Inflammation and fibrosis of the gallbladder wall were more common in tissue with gallbladder dysplasia/carcinoma than in benign tissue 12/25 (48%) versus 4/28 (12%) (p < 0.01) and in 13/21 (62%) versus 3/32 (9%) (p < 0.0001), respectively. Immunoreactivity for p53, Ki67, Cyclin D1 was detected in significantly more cases of dysplasia/carcinoma of the gallbladder than in non-cancerous epithelium. 2/19 (11%) of the samples were positive in non-cancerous epithelium versus 7/17 (41%) in dysplasia/carcinoma (p < 0.05) for TrxR1-v.2.3.5. Grx1 was down regulated; more specifically 15/19 (79%) positive cases in non-cancerous epithelium versus 7/17 (41%) in dysplasia/carcinoma. \n\n Conclusion: PSC patients have a frequency of gallbladder dysplasia/carcinoma of 30% in operative specimens. The overexpression of TrxR1-v2,3,5 and down regulation of Grx1 in dysplastic gallbladder epithelium suggest that these proteins should be further evaluated as possible future immunohistochemical markers in the early diagnosis of biliary malignancy in PSC. STN","prediction_labels":"HUMAN"},{"cleaned":"body mass index increase risk gallbladder cancer meta analysis 14 cohort studies background study sought appraise association raised body mass index bmi risk gallbladder cancer gbc performing meta analysis 14 cohort studies material methods eligible cohort studies selected searching pubmed embase inception may 26 2016 reference lists retrieved articles also consulted information screened two authors separately used fixed effects model calculate overall pooled risk estimates random effects model used identify heterogeneity results meta analysis incorporated 14 cohort studies nine papers deemed high quality based newcastle ottawa scale nos compared normal weight bmi 18 5 24 9 kg m overall pooled relative risks rr gbc 1 45 95 ci 1 30 1 61 excess body weight individuals bmi 25 kg m 1 10 95 ci 1 02 1 18 overweight persons bmi 25 29 9 kg m 1 69 95 ci 1 54 1 86 obese folks bmi 30 kg m higher risk gbc presented obese women women rr 1 78 95 ci 1 59 1 99 men rr 1 50 95 ci 1 25 1 79 positive relationship overweight gbc risk also displayed female rr 1 25 95 ci 1 11 1 40 male rr 1 01 95 ci 0 93 1 11 sensitivity analysis indicated stable results publication bias observed conclusions meta analysis 14 cohort studies demonstrated raised bmi dramatic association risk gbc especially women association overweight gbc men found pubmed","probabilities":0.9799733,"Title":"Body Mass Index Can Increase the Risk of Gallbladder Cancer: A Meta-Analysis of 14 Cohort Studies","Abstract":"BACKGROUND This study sought to appraise the association between raised body mass index (BMI) and the risk of gallbladder cancer (GBC) by performing a meta-analysis of 14 cohort studies. MATERIAL AND METHODS Eligible cohort studies were selected by searching PubMed and EMBASE from their inception to May 26, 2016, and the reference lists of retrieved articles were also consulted. The information was screened by two authors separately. We used a fixed-effects model to calculate the overall pooled risk estimates. A random-effects model was used to identify heterogeneity. RESULTS The meta-analysis incorporated 14 cohort studies. Nine papers were deemed to be of high quality based on the Newcastle-Ottawa Scale (NOS). Compared with normal weight (BMI 18.5-24.9 kg/m²), the overall pooled relative risks (RR) of GBC was 1.45 (95% CI 1.30-1.61) for excess body weight individuals (BMI ≥25 kg/m²); 1.10 (95% CI 1.02-1.18) for overweight persons (BMI 25-29.9 kg/m²) and 1.69(95% CI 1.54-1.86) for obese folks (BMI ≥30 kg/m²). A higher risk of GBC was presented in obese women (women: RR 1.78, 95% CI 1.59-1.99; men: RR 1.50, 95% CI 1.25-1.79). And a positive relationship between overweight and GBC risk was also displayed in female (RR 1.25, 95% CI 1.11-1.40), but not in male (RR 1.01, 95% CI 0.93-1.11). The sensitivity analysis indicated stable results, and no publication bias was observed. CONCLUSIONS This meta-analysis of 14 cohort studies demonstrated that raised BMI has a dramatic association with risk of GBC, especially in women. But, no association between overweight and GBC in men was found.","Source":"PubMed","category":"HUMAN","training_data":"Body Mass Index Can Increase the Risk of Gallbladder Cancer: A Meta-Analysis of 14 Cohort Studies BACKGROUND This study sought to appraise the association between raised body mass index (BMI) and the risk of gallbladder cancer (GBC) by performing a meta-analysis of 14 cohort studies. MATERIAL AND METHODS Eligible cohort studies were selected by searching PubMed and EMBASE from their inception to May 26, 2016, and the reference lists of retrieved articles were also consulted. The information was screened by two authors separately. We used a fixed-effects model to calculate the overall pooled risk estimates. A random-effects model was used to identify heterogeneity. RESULTS The meta-analysis incorporated 14 cohort studies. Nine papers were deemed to be of high quality based on the Newcastle-Ottawa Scale (NOS). Compared with normal weight (BMI 18.5-24.9 kg/m²), the overall pooled relative risks (RR) of GBC was 1.45 (95% CI 1.30-1.61) for excess body weight individuals (BMI ≥25 kg/m²); 1.10 (95% CI 1.02-1.18) for overweight persons (BMI 25-29.9 kg/m²) and 1.69(95% CI 1.54-1.86) for obese folks (BMI ≥30 kg/m²). A higher risk of GBC was presented in obese women (women: RR 1.78, 95% CI 1.59-1.99; men: RR 1.50, 95% CI 1.25-1.79). And a positive relationship between overweight and GBC risk was also displayed in female (RR 1.25, 95% CI 1.11-1.40), but not in male (RR 1.01, 95% CI 0.93-1.11). The sensitivity analysis indicated stable results, and no publication bias was observed. CONCLUSIONS This meta-analysis of 14 cohort studies demonstrated that raised BMI has a dramatic association with risk of GBC, especially in women. But, no association between overweight and GBC in men was found. PubMed","prediction_labels":"HUMAN"},{"cleaned":"portal vein resection management hilar cholangiocarcinoma background vascular reconstruction along major liver resection setting liver dysfunction caused biliary obstruction associated increased risk purpose report assess role portal vein resection reconstruction surgical management hilar cholangiocarcinoma study design ninety five patients hilar cholangiocarcinoma underwent resection 1999 2010 reviewed liver resections performed along biliary resection included 84 trisegmentectomies 63 right 21 left 11 lobectomies 8 left 3 right thirteen patients also simultaneous pancreaticoduodenectomy performed forty two patients underwent portal vein resection reconstruction five patients required reconstruction hepatic artery preoperative portal vein embolization used 38 patients results patients undergoing resection 5 mortality rate overall morbidity rate 36 patients underwent portal vein resection perioperative mortality morbidity similar portal vein resection median survival 38 months 95 ci 29 51 months 5 year survival rate 43 difference long term survival patients portal vein resection negative margins achieved 84 cases associated improved survival p 0 01 five year survival rate patients undergoing r0 resection 50 patients positive lymph nodes appeared worse 5 year survival rate patients node negative status 23 versus 49 however negative margin status associated improved survival multivariate analysis conclusions surgical resection hilar cholangiocarcinoma requires resection portal vein performed safely contraindication resection pubmed","probabilities":0.9799733,"Title":"Portal vein resection in management of hilar cholangiocarcinoma","Abstract":"BACKGROUND: Vascular reconstruction along with major liver resection in the setting of liver dysfunction caused by biliary obstruction can be associated with increased risk. The purpose of this report is to assess the role of portal vein resection and reconstruction in the surgical management of hilar cholangiocarcinoma. STUDY DESIGN: Ninety-five patients with hilar cholangiocarcinoma who underwent resection between 1999 and 2010 were reviewed. Liver resections performed along with biliary resection included 84 trisegmentectomies (63 right, 21 left) and 11 lobectomies (8 left, 3 right). Thirteen patients also had simultaneous pancreaticoduodenectomy performed. Forty-two patients underwent portal vein resection and reconstruction. Five patients required reconstruction of the hepatic artery. Preoperative portal vein embolization was used in 38 patients. RESULTS: Patients undergoing resection had a 5% mortality rate, with an overall morbidity rate of 36%. Patients who underwent portal vein resection had perioperative mortality and morbidity similar to those who did not have portal vein resection. Median survival was 38 months (95% CI, 29-51 months), with a 5-year survival rate of 43%. There was no difference in long-term survival between those patients who had portal vein resection and those that did not. Negative margins were achieved in 84% of cases and were associated with improved survival (p < 0.01). Five-year survival rate in patients undergoing R0 resection was 50%. Patients with positive lymph nodes appeared to have a worse 5-year survival rate than patients with node-negative status (23% versus 49%); however, only negative margin status was associated with improved survival by multivariate analysis. CONCLUSIONS: Surgical resection of hilar cholangiocarcinoma that requires resection of the portal vein can be performed safely and should not be a contraindication to resection.","Source":"PubMed","category":"HUMAN","training_data":"Portal vein resection in management of hilar cholangiocarcinoma BACKGROUND: Vascular reconstruction along with major liver resection in the setting of liver dysfunction caused by biliary obstruction can be associated with increased risk. The purpose of this report is to assess the role of portal vein resection and reconstruction in the surgical management of hilar cholangiocarcinoma. STUDY DESIGN: Ninety-five patients with hilar cholangiocarcinoma who underwent resection between 1999 and 2010 were reviewed. Liver resections performed along with biliary resection included 84 trisegmentectomies (63 right, 21 left) and 11 lobectomies (8 left, 3 right). Thirteen patients also had simultaneous pancreaticoduodenectomy performed. Forty-two patients underwent portal vein resection and reconstruction. Five patients required reconstruction of the hepatic artery. Preoperative portal vein embolization was used in 38 patients. RESULTS: Patients undergoing resection had a 5% mortality rate, with an overall morbidity rate of 36%. Patients who underwent portal vein resection had perioperative mortality and morbidity similar to those who did not have portal vein resection. Median survival was 38 months (95% CI, 29-51 months), with a 5-year survival rate of 43%. There was no difference in long-term survival between those patients who had portal vein resection and those that did not. Negative margins were achieved in 84% of cases and were associated with improved survival (p < 0.01). Five-year survival rate in patients undergoing R0 resection was 50%. Patients with positive lymph nodes appeared to have a worse 5-year survival rate than patients with node-negative status (23% versus 49%); however, only negative margin status was associated with improved survival by multivariate analysis. CONCLUSIONS: Surgical resection of hilar cholangiocarcinoma that requires resection of the portal vein can be performed safely and should not be a contraindication to resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"yttrium 90 radioembolization unresectable intrahepatic cholangiocarcinoma survival efficacy safety study purpose assess overall survival efficacy safety radioembolization yttrium 90 y90 unresectable standard chemorefractory intrahepatic cholangiocarcinoma icc methods patients unresectable standard chemorefractory icc treated y90 studied survival calculated date first y90 procedure tumor response assessed response evaluation criteria solid tumors criteria follow computed tomography magnetic resonance imaging scans national cancer institute common terminology criteria nci ctcae version 3 used complications statistical analysis performed kaplan meier estimator log rank test results nineteen patients underwent total 24 resin based y90 treatments median survival time diagnosis first y90 procedure 752 193 95 confidence interval ci 374 1130 345 128 95 ci 95 595 days respectively median survival eastern cooperative oncology group ecog performance status 1 n 15 ecog performance status 2 n 4 450 190 95 ci 78 822 345 227 95 ci 0 790 days respectively p 214 patients extrahepatic metastasis n 11 median survival 404 309 95 ci 0 1010 days versus 345 117 95 ci 115 575 days patients without metastasis n 8 p 491 mortality reported within 30 days first y90 radioembolization one patient developed grade 3 thrombocytopenia assessed nci ctcae fatigue transient abdominal pain observed 4 21 6 32 patients respectively conclusion y90 radioembolization effective unresectable standard chemorefractory icc google scholar","probabilities":0.9799733,"Title":"Yttrium-90 Radioembolization For Unresectable Intrahepatic Cholangiocarcinoma: Survival Efficacy And Safety Study","Abstract":"Purpose\nTo assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC).\nMethods\nPatients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan–Meier estimator by the log rank test.\nResults\nNineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 ± 193 [95 % confidence interval (CI) 374–1130] and 345 ± 128 (95 % CI 95–595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 ± 190 (95 % CI 78–822) and 345 ± 227 (95 % CI 0–790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 ± 309 (95 % CI 0–1010) days versus 345 ± 117 (95 % CI 115–575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively.\nConclusion\nY90 radioembolization is effective for unresectable standard-chemorefractory ICC.","Source":"Google Scholar","category":"HUMAN","training_data":"Yttrium-90 Radioembolization For Unresectable Intrahepatic Cholangiocarcinoma: Survival Efficacy And Safety Study Purpose\nTo assess the overall survival, efficacy, and safety of radioembolization with yttrium-90 (Y90) for unresectable standard-chemorefractory intrahepatic cholangiocarcinoma (ICC).\nMethods\nPatients with unresectable standard-chemorefractory ICC treated with Y90 were studied. Survival was calculated from the date of first Y90 procedure. Tumor response was assessed with the Response Evaluation Criteria in Solid Tumors criteria on follow-up computed tomography or magnetic resonance imaging scans. National Cancer Institute Common Terminology Criteria (NCI CTCAE), version 3, were used for complications. Statistical analysis was performed by the Kaplan–Meier estimator by the log rank test.\nResults\nNineteen patients underwent a total of 24 resin-based Y90 treatments. Median survival from the time of diagnosis and first Y90 procedure was 752 ± 193 [95 % confidence interval (CI) 374–1130] and 345 ± 128 (95 % CI 95–595) days, respectively. Median survival with Eastern Cooperative Oncology Group (ECOG) performance status 1 (n = 15) and ECOG performance status 2 (n = 4) was 450 ± 190 (95 % CI 78–822) and 345 ± 227 (95 % CI 0–790) days, respectively (p = .214). Patients with extrahepatic metastasis (n = 11) had a median survival of 404 ± 309 (95 % CI 0–1010) days versus 345 ± 117 (95 % CI 115–575) days for patients without metastasis (n = 8) (p = .491). No mortality was reported within 30 days from first Y90 radioembolization. One patient developed grade 3 thrombocytopenia as assessed by NCI CTCAE. Fatigue and transient abdominal pain were observed in 4 (21 %) and 6 (32 %) patients, respectively.\nConclusion\nY90 radioembolization is effective for unresectable standard-chemorefractory ICC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"loss mtss1 expression independent prognostic factor hilar cholangiocarcinoma metastasis suppressor 1 mtss1 novel metastasis suppressor gene variety cancers study aimed detect mtss1 expression normal cancerous tissue specimens chinese patients hilarcholangiocarcinoma determine association clinicopathological parameters survival tissue microarrays containing normal tumor specimens constructed using paraffin blocks 61 patients immunohistochemical analysis mtss1 expression subgroup tissues verified western blot analysis mtss1 protein expressed 24 61 cases 39 3 tumor tissues compared 22 26 84 6 non neoplastic bile duct epithelium 26 26 100 adjacent normal liver cells loss mtss1 expression associated lymph node metastases cholangiocelluarcarcinoma tumorcellde differentiation mtss1 expression inversely associated tumor recurrence overall survival patients univariate multivariate analyses mtss1 expression significantly decreased human hilarcholangiocarcinoma lost mtss1 expression associated pooroverall survival tumor recurrences cholangiocarcinoma patients thus mtss1 expression represents independent predictor tumor recurrence overall survival patients cholangiocarcinoma stn","probabilities":1.0,"Title":"Loss Of Mtss1 Expression Is An Independent Prognostic Factor For Hilar Cholangiocarcinoma","Abstract":"Metastasis suppressor 1 (MTSS1) is a novel metastasis suppressor gene in a variety of cancers. This study aimed to detect MTSS1 expression in normal and cancerous tissue specimens from Chinese patients with hilarcholangiocarcinoma to determine the association with clinicopathological parameters and survival. Tissue microarrays containing normal and tumor specimens were constructed using paraffin blocks from 61 patients for immunohistochemical analysis of MTSS1 expression. A subgroup of these tissues was verified by Western blot analysis. MTSS1 protein was expressed in 24 of 61 cases (39.3 %) of tumor tissues, compared to that in 22 of 26 (84.6 %) of non-neoplastic bile duct epithelium and in 26 of 26 (100 %) of adjacent normal liver cells. Loss of MTSS1 expression was associated with lymph node metastases of cholangiocelluarcarcinoma and tumorcellde-differentiation.MTSS1 expression inversely associated with tumor recurrence and overall survival of the patients by univariate and multivariate analyses. MTSS1 expression was significantly decreased in human hilarcholangiocarcinoma and lost MTSS1 expression was associated with pooroverall survival and tumor recurrences in cholangiocarcinoma patients. Thus, MTSS1 expression represents an independent predictor for tumor recurrence and overall survival in patients with cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Loss Of Mtss1 Expression Is An Independent Prognostic Factor For Hilar Cholangiocarcinoma Metastasis suppressor 1 (MTSS1) is a novel metastasis suppressor gene in a variety of cancers. This study aimed to detect MTSS1 expression in normal and cancerous tissue specimens from Chinese patients with hilarcholangiocarcinoma to determine the association with clinicopathological parameters and survival. Tissue microarrays containing normal and tumor specimens were constructed using paraffin blocks from 61 patients for immunohistochemical analysis of MTSS1 expression. A subgroup of these tissues was verified by Western blot analysis. MTSS1 protein was expressed in 24 of 61 cases (39.3 %) of tumor tissues, compared to that in 22 of 26 (84.6 %) of non-neoplastic bile duct epithelium and in 26 of 26 (100 %) of adjacent normal liver cells. Loss of MTSS1 expression was associated with lymph node metastases of cholangiocelluarcarcinoma and tumorcellde-differentiation.MTSS1 expression inversely associated with tumor recurrence and overall survival of the patients by univariate and multivariate analyses. MTSS1 expression was significantly decreased in human hilarcholangiocarcinoma and lost MTSS1 expression was associated with pooroverall survival and tumor recurrences in cholangiocarcinoma patients. Thus, MTSS1 expression represents an independent predictor for tumor recurrence and overall survival in patients with cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"ddr2 ifitm1 prognostic markers gallbladder squamous cell adenosquamous carcinomas adenocarcinomas study conducted investigate expressions ddr2 ifitm1 clinical pathological significances rare type squamous cell adenosquamous carcinomas sc asc ordinary adenocarcinomas ac gallbladder cancers ddr2 ifitm1 expression examined 69 sc ascs 146 acs using envision immunohistochemistry results showed percentage positive ddr2 ifitm1 expression significantly higher sc asc patients high tnm stage lymph node metastasis invasion resection surgery compared patients low tnm stages lymph node metastasis invasion resection surgery p 0 05 p 0 01 positive rate ddr2 significantly higher sc asc patients large tumor sizes patients small tumor sizes p 0 05 percentage positive ddr2 ifitm1 expressions significantly higher ac patients high tnm stages didn receive resection surgery compared patients low tnm stages receive resection surgery p 0 05 p 0 01 positive rate ifitm1 significantly higher ac patients lymph node metastasis invasion patients without metastasis invasion p 0 05 positive ddr2 ifitm1 expression closely associated decreased overall survival sc asc ac patients p 0 05 p 0 01 auc analysis showed ddr2 ifitm1 sensitive specific diagnosis sc asc auc 0 740 auc 0 733 respectively ac auc 0 710 auc 0 741 respectively conclusion positive ddr2 ifitm1 expression marker clinical severity poor prognosis diagnosis gallbladder sc asc ac pubmed","probabilities":0.962963,"Title":"DDR2 and IFITM1 Are Prognostic Markers in Gallbladder Squamous Cell/Adenosquamous Carcinomas and Adenocarcinomas","Abstract":"This study was conducted to investigate the expressions of DDR2 and IFITM1 and their clinical and pathological significances in the rare type squamous cell/adenosquamous carcinomas (SC/ASC) and ordinary adenocarcinomas (AC) of gallbladder cancers. DDR2 and IFITM1 expression was examined in 69 SC/ASCs and 146 ACs using EnVision immunohistochemistry. Results showed that the percentage of positive DDR2 and IFITM1 expression was significantly higher in SC/ASC patients with high TNM stage, lymph node metastasis, invasion, and no resection surgery compared to patients with low TNM stages, no lymph node metastasis, no invasion, and resection surgery (P < 0.05 or P < 0.01). The positive rate of DDR2 was significantly higher in SC/ASC patients with large tumor sizes than patients with small tumor sizes (p < 0.05). The percentage of positive DDR2 and IFITM1 expressions was significantly higher in AC patients with high TNM stages that didn't receive resection surgery compared to patients with low TNM stages that did receive resection surgery (P < 0.05 or P < 0.01). The positive rate of IFITM1 was significantly higher in AC patients with lymph node metastasis and invasion than in patients without metastasis and invasion (p < 0.05). Positive DDR2 and IFITM1 expression was closely associated with a decreased overall survival in SC/ASC and AC patients (P < 0.05 or P < 0.01). AUC analysis showed that DDR2 and IFITM1 was sensitive and specific for the diagnosis of SC/ASC (AUC = 0.740 and AUC =0.733, respectively) and AC (AUC = 0.710 and AUC =0.741, respectively). In conclusion, positive DDR2 and IFITM1 expression is a marker for the clinical severity, poor prognosis, and diagnosis of gallbladder SC/ASC and AC.","Source":"PubMed","category":"HUMAN","training_data":"DDR2 and IFITM1 Are Prognostic Markers in Gallbladder Squamous Cell/Adenosquamous Carcinomas and Adenocarcinomas This study was conducted to investigate the expressions of DDR2 and IFITM1 and their clinical and pathological significances in the rare type squamous cell/adenosquamous carcinomas (SC/ASC) and ordinary adenocarcinomas (AC) of gallbladder cancers. DDR2 and IFITM1 expression was examined in 69 SC/ASCs and 146 ACs using EnVision immunohistochemistry. Results showed that the percentage of positive DDR2 and IFITM1 expression was significantly higher in SC/ASC patients with high TNM stage, lymph node metastasis, invasion, and no resection surgery compared to patients with low TNM stages, no lymph node metastasis, no invasion, and resection surgery (P < 0.05 or P < 0.01). The positive rate of DDR2 was significantly higher in SC/ASC patients with large tumor sizes than patients with small tumor sizes (p < 0.05). The percentage of positive DDR2 and IFITM1 expressions was significantly higher in AC patients with high TNM stages that didn't receive resection surgery compared to patients with low TNM stages that did receive resection surgery (P < 0.05 or P < 0.01). The positive rate of IFITM1 was significantly higher in AC patients with lymph node metastasis and invasion than in patients without metastasis and invasion (p < 0.05). Positive DDR2 and IFITM1 expression was closely associated with a decreased overall survival in SC/ASC and AC patients (P < 0.05 or P < 0.01). AUC analysis showed that DDR2 and IFITM1 was sensitive and specific for the diagnosis of SC/ASC (AUC = 0.740 and AUC =0.733, respectively) and AC (AUC = 0.710 and AUC =0.741, respectively). In conclusion, positive DDR2 and IFITM1 expression is a marker for the clinical severity, poor prognosis, and diagnosis of gallbladder SC/ASC and AC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"r0 r1 r2 resection associated better survival palliative photodynamic therapy biliary tract cancer background need better management strategies improve survival quality life patients biliary tract cancer btc aim assess prognostic factors survival large non selective cohort patients btc method compared outcomes 321 patients final diagnosis btc cholangiocarcinoma n 237 gallbladder cancer n 84 seen tertiary referral cancer centre 1998 2007 survival according disease stage treatment category compared using log rank testing cox regression analysis used determine independent prognostic factors results eighty nine 28 patients underwent surgical intervention curative intent 38 r0 resections among 321 patients 34 given chemo radiotherapy 14 palliated photodynamic therapy pdt 37 biliary drainage procedures alone overall median survival 9 months 3 year survival 14 r0 resective surgery conferred favourable outcome 3 year survival 57 although patients palliated pdt advanced clinical stages survival similar treated attempted curative surgery positive resection margins multivariable analysis treatment modality serum carbohydrate associated antigen 19 9 distant metastases vascular involvement independent prognostic indicators survival conclusion large uk series btc palliative pdt resulted survival similar curatively intended r1 r2 resections surgery conferred survival advantage patients r0 resection margins emphasising need accurate pre operative staging pubmed","probabilities":0.9799733,"Title":"R0 but not R1/R2 resection is associated with better survival than palliative photodynamic therapy in biliary tract cancer","Abstract":"BACKGROUND: There is a need for better management strategies to improve the survival and quality of life in patients with biliary tract cancer (BTC). AIM: To assess prognostic factors for survival in a large, non-selective cohort of patients with BTC. METHOD: We compared outcomes in 321 patients with a final diagnosis of BTC (cholangiocarcinoma n = 237, gallbladder cancer n = 84) seen in a tertiary referral cancer centre between 1998 and 2007. Survival according to disease stage and treatment category was compared using log-rank testing. Cox's regression analysis was used to determine independent prognostic factors. RESULTS: Eighty-nine (28%) patients underwent a surgical intervention with curative intent, of whom 38% had R0 resections. Among the 321 patients, 34% were given chemo- and/or radiotherapy, 14% were palliated with photodynamic therapy (PDT) and 37% with biliary drainage procedures alone. The overall median survival was 9 months (3-year survival, 14%). R0-resective surgery conferred the most favourable outcome (3-year survival, 57%). Although patients palliated with PDT had more advanced clinical T-stages, their survival was similar to those treated with attempted curative surgery but who had positive resection margins. On multivariable analysis, treatment modality, serum carbohydrate-associated antigen 19-9, distant metastases and vascular involvement were independent prognostic indicators of survival. CONCLUSION: In this large UK series of BTC, palliative PDT resulted in survival similar to those with curatively intended R1/R2 resections. Surgery conferred a survival advantage only in patients with R0 resection margins, emphasising the need for accurate pre-operative staging.","Source":"PubMed","category":"HUMAN","training_data":"R0 but not R1/R2 resection is associated with better survival than palliative photodynamic therapy in biliary tract cancer BACKGROUND: There is a need for better management strategies to improve the survival and quality of life in patients with biliary tract cancer (BTC). AIM: To assess prognostic factors for survival in a large, non-selective cohort of patients with BTC. METHOD: We compared outcomes in 321 patients with a final diagnosis of BTC (cholangiocarcinoma n = 237, gallbladder cancer n = 84) seen in a tertiary referral cancer centre between 1998 and 2007. Survival according to disease stage and treatment category was compared using log-rank testing. Cox's regression analysis was used to determine independent prognostic factors. RESULTS: Eighty-nine (28%) patients underwent a surgical intervention with curative intent, of whom 38% had R0 resections. Among the 321 patients, 34% were given chemo- and/or radiotherapy, 14% were palliated with photodynamic therapy (PDT) and 37% with biliary drainage procedures alone. The overall median survival was 9 months (3-year survival, 14%). R0-resective surgery conferred the most favourable outcome (3-year survival, 57%). Although patients palliated with PDT had more advanced clinical T-stages, their survival was similar to those treated with attempted curative surgery but who had positive resection margins. On multivariable analysis, treatment modality, serum carbohydrate-associated antigen 19-9, distant metastases and vascular involvement were independent prognostic indicators of survival. CONCLUSION: In this large UK series of BTC, palliative PDT resulted in survival similar to those with curatively intended R1/R2 resections. Surgery conferred a survival advantage only in patients with R0 resection margins, emphasising the need for accurate pre-operative staging. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment recurrent intrahepatic cholangiocarcinoma background aims study evaluate risk factors recurrence following hepatectomy curative intent intrahepatic cholangiocarcinoma icc predictors survival intrahepatic recurrence methods patients icc underwent liver resection january 1997 august 2011 single centre analysed retrospectively clinicopathological factors likely influence recurrence postrecurrence survival assessed univariable multivariable analysis results total 87 patients analysed r0 resection achieved 65 patients 75 per cent eighty three patients survived 1 month resection median survival 33 months 1 3 5 year actuarial survival rates 79 47 31 per cent respectively recurrence occurred 45 54 per cent 83 patients frequently liver 25 patients satellite nodules odds ratio 8 17 95 per cent confidence interval 1 38 48 53 p 0 021 hilar lymph node metastases 5 24 1 07 25 75 p 0 041 perineural invasion 9 68 1 07 87 54 p 0 043 identified independent risk factors recurrence repeat hepatectomy p 0 003 intra arterial yttrium 90 radiotherapy p 0 048 associated longer survival intrahepatic recurrence conclusion satellite nodules hilar lymph node metastases perineural invasion risk factors recurrence following resection curative intent icc repeat hepatectomy labelled yttrium 90 radiotherapy may improve survival intrahepatic recurrence pubmed","probabilities":0.9799733,"Title":"Treatment of recurrent intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: The aims of this study were to evaluate risk factors for recurrence following hepatectomy with curative intent for intrahepatic cholangiocarcinoma (ICC), and predictors of survival after intrahepatic recurrence. METHODS: All patients with ICC who underwent liver resection between January 1997 and August 2011 in a single centre were analysed retrospectively. Clinicopathological factors likely to influence recurrence and postrecurrence survival were assessed by univariable and multivariable analysis. RESULTS: A total of 87 patients were analysed. R0 resection was achieved in 65 patients (75 per cent). Eighty-three patients survived more than 1 month after resection. Median survival was 33 months, with 1-, 3- and 5-year actuarial survival rates of 79, 47 and 31 per cent respectively. Recurrence occurred in 45 (54 per cent) of the 83 patients, most frequently in the liver (25 patients). Satellite nodules (odds ratio (OR) 8·17, 95 per cent confidence interval 1·38 to 48·53; P = 0·021), hilar lymph node metastases (OR 5·24, 1·07 to 25·75; P = 0·041) and perineural invasion (OR 9·68, 1·07 to 87·54; P = 0·043) were identified as independent risk factors for recurrence. Repeat hepatectomy (P = 0·003) and intra-arterial yttrium-90 radiotherapy (P = 0·048) were associated with longer survival after intrahepatic recurrence. CONCLUSION: Satellite nodules, hilar lymph node metastases and perineural invasion are risk factors for recurrence following resection with curative intent for ICC. Repeat hepatectomy and labelled yttrium-90 radiotherapy may improve survival after intrahepatic recurrence.","Source":"PubMed","category":"HUMAN","training_data":"Treatment of recurrent intrahepatic cholangiocarcinoma BACKGROUND: The aims of this study were to evaluate risk factors for recurrence following hepatectomy with curative intent for intrahepatic cholangiocarcinoma (ICC), and predictors of survival after intrahepatic recurrence. METHODS: All patients with ICC who underwent liver resection between January 1997 and August 2011 in a single centre were analysed retrospectively. Clinicopathological factors likely to influence recurrence and postrecurrence survival were assessed by univariable and multivariable analysis. RESULTS: A total of 87 patients were analysed. R0 resection was achieved in 65 patients (75 per cent). Eighty-three patients survived more than 1 month after resection. Median survival was 33 months, with 1-, 3- and 5-year actuarial survival rates of 79, 47 and 31 per cent respectively. Recurrence occurred in 45 (54 per cent) of the 83 patients, most frequently in the liver (25 patients). Satellite nodules (odds ratio (OR) 8·17, 95 per cent confidence interval 1·38 to 48·53; P = 0·021), hilar lymph node metastases (OR 5·24, 1·07 to 25·75; P = 0·041) and perineural invasion (OR 9·68, 1·07 to 87·54; P = 0·043) were identified as independent risk factors for recurrence. Repeat hepatectomy (P = 0·003) and intra-arterial yttrium-90 radiotherapy (P = 0·048) were associated with longer survival after intrahepatic recurrence. CONCLUSION: Satellite nodules, hilar lymph node metastases and perineural invasion are risk factors for recurrence following resection with curative intent for ICC. Repeat hepatectomy and labelled yttrium-90 radiotherapy may improve survival after intrahepatic recurrence. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cd24 expression predicts distant metastasis extrahepatic bile duct cancer aim evaluate prognostic significance cd24 expression patients undergoing adjuvant chemoradiotherapy extrahepatic bile duct ehbd cancer methods eighty four patients ehbd cancer underwent curative resection followed adjuvant chemoradiotherapy enrolled study postoperative radiotherapy delivered tumor bed regional lymph nodes median 40 gy range 40 56 gy patients also received fluoropyrimidine chemotherapy radiosensitization radiotherapy cd24 expression assessed immunohistochemical staining tissue microarray clinicopathologic factors well cd24 expression evaluated multivariate analysis clinical outcomes including loco regional recurrence distant metastasis free overall survival results cd24 expressed 36 patients 42 9 cd24 expression associated distant metastasis loco regional recurrence overall survival 5 year distant metastasis free survival rates 55 1 29 0 patients negative positive expression respectively p 0 0100 multivariate analysis incorporating n stage histologic differentiation cd24 expression n stage significant factor predicting distant metastasis free survival p 0 0089 cd24 expression borderline significance p 0 0733 subgroup analysis cd24 expression significantly associated 5 year distant metastasis free survival node positive patients 38 4 negative expression vs 0 positive expression p 0 0110 node negative patients 62 0 negative expression vs 64 0 positive expression p 0 8599 conclusion cd24 expression significant predictor distant metastasis patients undergoing curative resection followed adjuvant chemoradiotherapy especially node positive ehbd cancer pubmed","probabilities":0.7966102,"Title":"CD24 expression predicts distant metastasis in extrahepatic bile duct cancer","Abstract":"AIM: To evaluate the prognostic significance of CD24 expression in patients undergoing adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. METHODS: Eighty-four patients with EHBD cancer who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled in this study. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to a median of 40 Gy (range: 40-56 Gy). All patients also received fluoropyrimidine chemotherapy for radiosensitization during radiotherapy. CD24 expression was assessed with immunohistochemical staining on tissue microarray. Clinicopathologic factors as well as CD24 expression were evaluated in multivariate analysis for clinical outcomes including loco-regional recurrence, distant metastasis-free and overall survival. RESULTS: CD24 was expressed in 36 patients (42.9%). CD24 expression was associated with distant metastasis, but not with loco-regional recurrence nor with overall survival. The 5-year distant metastasis-free survival rates were 55.1% and 29.0% in patients with negative and positive expression, respectively (P = 0.0100). On multivariate analysis incorporating N stage, histologic differentiation and CD24 expression, N stage was the only significant factor predicting distant metastasis-free survival (P = 0.0089), while CD24 expression had borderline significance (P = 0.0733). In subgroup analysis, CD24 expression was significantly associated with 5-year distant metastasis-free survival in node-positive patients (38.4% with negative expression vs 0% with positive expression, P = 0.0110), but not in node-negative patients (62.0% with negative expression vs 64.0% with positive expression, P = 0.8599). CONCLUSION: CD24 expression was a significant predictor of distant metastasis for patients undergoing curative resection followed by adjuvant chemoradiotherapy especially for node-positive EHBD cancer.","Source":"PubMed","category":"HUMAN","training_data":"CD24 expression predicts distant metastasis in extrahepatic bile duct cancer AIM: To evaluate the prognostic significance of CD24 expression in patients undergoing adjuvant chemoradiotherapy for extrahepatic bile duct (EHBD) cancer. METHODS: Eighty-four patients with EHBD cancer who underwent curative resection followed by adjuvant chemoradiotherapy were enrolled in this study. Postoperative radiotherapy was delivered to the tumor bed and regional lymph nodes up to a median of 40 Gy (range: 40-56 Gy). All patients also received fluoropyrimidine chemotherapy for radiosensitization during radiotherapy. CD24 expression was assessed with immunohistochemical staining on tissue microarray. Clinicopathologic factors as well as CD24 expression were evaluated in multivariate analysis for clinical outcomes including loco-regional recurrence, distant metastasis-free and overall survival. RESULTS: CD24 was expressed in 36 patients (42.9%). CD24 expression was associated with distant metastasis, but not with loco-regional recurrence nor with overall survival. The 5-year distant metastasis-free survival rates were 55.1% and 29.0% in patients with negative and positive expression, respectively (P = 0.0100). On multivariate analysis incorporating N stage, histologic differentiation and CD24 expression, N stage was the only significant factor predicting distant metastasis-free survival (P = 0.0089), while CD24 expression had borderline significance (P = 0.0733). In subgroup analysis, CD24 expression was significantly associated with 5-year distant metastasis-free survival in node-positive patients (38.4% with negative expression vs 0% with positive expression, P = 0.0110), but not in node-negative patients (62.0% with negative expression vs 64.0% with positive expression, P = 0.8599). CONCLUSION: CD24 expression was a significant predictor of distant metastasis for patients undergoing curative resection followed by adjuvant chemoradiotherapy especially for node-positive EHBD cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radiofrequency ablation treatment unresectable intrahepatic cholangiocarcinoma systematic review meta analysis purpose study perform meta analysis systematic review clinical efficacy safety radiofrequency rf ablation treatment intrahepatic cholangiocarcinoma icc comprehensive literature search ovid medline embase identified studies describing use rf ablation treatment icc data describing overall survival local tumor progression complications collected seven observational studies comprised 84 patients reviewed pooled 1 year 3 year 5 year survival rates 82 95 confidence interval ci 72 90 47 95 ci 28 65 24 95 ci 11 40 one 2 major complications occurred 4 studies 1 patient died liver abscess subsequent sepsis despite treatment percutaneous drainage antibiotics rf ablation locoregional treatment option prolongs survival rates patients icc ineligible surgery pubmed","probabilities":0.9799733,"Title":"Radiofrequency ablation in the treatment of unresectable intrahepatic cholangiocarcinoma: systematic review and meta-analysis","Abstract":"The purpose of this study was to perform a meta-analysis and systematic review of the clinical efficacy and safety of radiofrequency (RF) ablation in the treatment of intrahepatic cholangiocarcinoma (ICC). A comprehensive literature search of Ovid MEDLINE and EMBASE identified studies describing the use of RF ablation in the treatment of ICC. Data describing overall survival, local tumor progression, and complications were collected. Seven observational studies that comprised 84 patients were reviewed. The pooled 1-year, 3-year, and 5-year survival rates were 82% (95% confidence interval [CI], 72%-90%), 47% (95% CI, 28%-65%), and 24% (95% CI, 11%-40%). One or 2 major complications occurred in 4 studies, and 1 patient died of liver abscess and subsequent sepsis despite treatment with percutaneous drainage and antibiotics. RF ablation is a locoregional treatment option that prolongs survival rates in patients with ICC who are ineligible for surgery.","Source":"PubMed","category":"HUMAN","training_data":"Radiofrequency ablation in the treatment of unresectable intrahepatic cholangiocarcinoma: systematic review and meta-analysis The purpose of this study was to perform a meta-analysis and systematic review of the clinical efficacy and safety of radiofrequency (RF) ablation in the treatment of intrahepatic cholangiocarcinoma (ICC). A comprehensive literature search of Ovid MEDLINE and EMBASE identified studies describing the use of RF ablation in the treatment of ICC. Data describing overall survival, local tumor progression, and complications were collected. Seven observational studies that comprised 84 patients were reviewed. The pooled 1-year, 3-year, and 5-year survival rates were 82% (95% confidence interval [CI], 72%-90%), 47% (95% CI, 28%-65%), and 24% (95% CI, 11%-40%). One or 2 major complications occurred in 4 studies, and 1 patient died of liver abscess and subsequent sepsis despite treatment with percutaneous drainage and antibiotics. RF ablation is a locoregional treatment option that prolongs survival rates in patients with ICC who are ineligible for surgery. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors benefits adjuvant therapy ampullary cancer following pancreatoduodenectomy systematic review meta analysis ampullary cancer relatively rare gastrointestinal malignancy purpose study evaluate prognostic factors survival assess benefits adjuvant therapy following pancreaticoduodenectomy entity medline embase databases searched identify eligible studies january 2000 august 2019 review manager 5 3 statistical software used meta analysis 71 studies met inclusion criteria included analysis total 8280 patients median range 5 year overall survival disease free survival rates 58 32 82 51 28 73 respectively meta analysis age 65 years diagnosis tumor size 20 mm poor differentiation pancreaticobiliary histotype pt3 4 stage disease presence metastatic lymph node number metastatic nodes perineural invasion lymphovascular invasion vascular invasion pancreatic invasion positive surgical margins independently associated worse overall survival whereas adjuvant therapy associated improved overall survival summary patients ampullary cancer undergoing pancreaticoduodenectomy tumor factors main predictors worse survival adjuvant treatment confers survival benefit stn","probabilities":0.9799733,"Title":"Prognostic Factors And Benefits Of Adjuvant Therapy For Ampullary Cancer Following Pancreatoduodenectomy: A Systematic Review And Meta-Analysis","Abstract":"Ampullary cancer is a relatively rare gastrointestinal malignancy. The purpose of this study was to evaluate prognostic factors for survival and assess the benefits of adjuvant therapy following pancreaticoduodenectomy for this entity. Medline and EMBASE databases were searched to identify eligible studies from January 2000 to August 2019. Review Manager 5.3 statistical software was used for meta-analysis. 71 studies met the inclusion criteria and were included in the analysis for a total of 8280 patients. The median (range) 5-year overall survival and disease-free survival rates were 58% (32-82%) and 51% (28-73%) respectively. In meta-analysis, age >65 years at diagnosis, tumor size >20 mm, poor differentiation, pancreaticobiliary histotype, pT3-4 stage disease, presence of metastatic lymph node, number of metastatic nodes, perineural invasion, lymphovascular invasion, vascular invasion, pancreatic invasion, and positive surgical margins were independently associated with worse overall survival, whereas adjuvant therapy was associated with improved overall survival. In summary, in patients with ampullary cancer undergoing pancreaticoduodenectomy, tumor factors are the main predictors of worse survival and adjuvant treatment confers a survival benefit.","Source":"STN","category":"HUMAN","training_data":"Prognostic Factors And Benefits Of Adjuvant Therapy For Ampullary Cancer Following Pancreatoduodenectomy: A Systematic Review And Meta-Analysis Ampullary cancer is a relatively rare gastrointestinal malignancy. The purpose of this study was to evaluate prognostic factors for survival and assess the benefits of adjuvant therapy following pancreaticoduodenectomy for this entity. Medline and EMBASE databases were searched to identify eligible studies from January 2000 to August 2019. Review Manager 5.3 statistical software was used for meta-analysis. 71 studies met the inclusion criteria and were included in the analysis for a total of 8280 patients. The median (range) 5-year overall survival and disease-free survival rates were 58% (32-82%) and 51% (28-73%) respectively. In meta-analysis, age >65 years at diagnosis, tumor size >20 mm, poor differentiation, pancreaticobiliary histotype, pT3-4 stage disease, presence of metastatic lymph node, number of metastatic nodes, perineural invasion, lymphovascular invasion, vascular invasion, pancreatic invasion, and positive surgical margins were independently associated with worse overall survival, whereas adjuvant therapy was associated with improved overall survival. In summary, in patients with ampullary cancer undergoing pancreaticoduodenectomy, tumor factors are the main predictors of worse survival and adjuvant treatment confers a survival benefit. STN","prediction_labels":"HUMAN"},{"cleaned":"biliary tract cancer registry japan 2008 2013 background present study analyzed biliary tract cancer patients registered 2008 2013 japan evaluated outcomes biliary tract cancer methods total 18 606 patients registered 2008 2013 cases analyzed regard patient survival according contiguous extent primary tumor node metastasis tumor stage using 3rd english edition japanese classification biliary tract cancers results five year survival rates 39 8 gallbladder cancer 24 2 perihilar bile duct cancer 39 1 distal bile duct cancer 61 3 ampullary region cancer significant differences observed newly introduced subdivisions new japanese classification tumoral sites except gallbladder cancer survival rate patients 13a metastasis significantly higher patients distant lymph node metastasis conclusions new japanese classification adopted 7th edition staging system developed union international cancer control staging system however numerous aspects classification systems remain unvalidated present analysis demonstrated significance proportion factor subdivisions classifications regional lymph nodes cases gallbladder cancer new japanese classification pubmed","probabilities":0.9799733,"Title":"Biliary tract cancer registry in Japan from 2008 to 2013","Abstract":"BACKGROUND: The present study analyzed biliary tract cancer patients registered from 2008 to 2013 in Japan and evaluated the outcomes of biliary tract cancer. METHODS: A total of 18,606 patients were registered from 2008 to 2013. Cases were analyzed with regard to patient survival according to contiguous extent of the primary tumor (T), node metastasis, and tumor stage using the 3rd English edition of the Japanese classification of the biliary tract cancers. RESULTS: Five-year survival rates were 39.8% for gallbladder cancer, 24.2% for perihilar bile duct cancer, 39.1% for distal bile duct cancer, and 61.3% for ampullary region cancer. Significant differences were observed between newly introduced subdivisions in the new Japanese classification for all tumoral sites except gallbladder cancer. The survival rate in patients with #13a metastasis was significantly higher than in patients with distant lymph node metastasis. CONCLUSIONS: The new Japanese classification adopted the 7th edition of staging system developed by the Union for International Cancer Control staging system. However, numerous aspects of these classification systems remain unvalidated. The present analysis demonstrated the significance of a proportion of T factor subdivisions and classifications of regional lymph nodes in cases of gallbladder cancer in the new Japanese classification.","Source":"PubMed","category":"HUMAN","training_data":"Biliary tract cancer registry in Japan from 2008 to 2013 BACKGROUND: The present study analyzed biliary tract cancer patients registered from 2008 to 2013 in Japan and evaluated the outcomes of biliary tract cancer. METHODS: A total of 18,606 patients were registered from 2008 to 2013. Cases were analyzed with regard to patient survival according to contiguous extent of the primary tumor (T), node metastasis, and tumor stage using the 3rd English edition of the Japanese classification of the biliary tract cancers. RESULTS: Five-year survival rates were 39.8% for gallbladder cancer, 24.2% for perihilar bile duct cancer, 39.1% for distal bile duct cancer, and 61.3% for ampullary region cancer. Significant differences were observed between newly introduced subdivisions in the new Japanese classification for all tumoral sites except gallbladder cancer. The survival rate in patients with #13a metastasis was significantly higher than in patients with distant lymph node metastasis. CONCLUSIONS: The new Japanese classification adopted the 7th edition of staging system developed by the Union for International Cancer Control staging system. However, numerous aspects of these classification systems remain unvalidated. The present analysis demonstrated the significance of a proportion of T factor subdivisions and classifications of regional lymph nodes in cases of gallbladder cancer in the new Japanese classification. PubMed","prediction_labels":"HUMAN"},{"cleaned":"relationship vegetable fruit consumption gallbladder bile duct cancer population based cohort study japan vegetable fruit consumption may protective effect several types cancers however effect biliary cancers unclear investigated association vegetable fruit consumption risks gallbladder cancer gbc intrahepatic bile duct cancer ihbdc extrahepatic bile duct cancer ehbdc population based prospective cohort study japan hazard ratios hrs 95 confidence intervals cis calculated using cox proportional hazard model exposure level categorized quartiles lowest group used reference total 80 371 people aged 45 74 years enrolled 1995 1999 followed 1 158 632 person years 2012 133 gbc 99 ihbdc 161 ehbdc cases identified increased consumption total vegetable fruit significantly associated decreased risk ehbdc hr 0 49 95 ci 0 29 0 81 highest group p trend 0 005 analysis relevant nutrients significantly decreased risk ehbdc associated folate insoluble fiber hr 0 48 0 53 95 ci 0 28 0 85 0 31 0 88 highest group p trend 0 010 0 023 respectively significant trend decreased ehbdc risk associated vitamin c observed p trend 0 029 decreased risk gbc ihbdc found findings suggest increased vegetable fruit consumption may decrease risk ehbdc folate vitamin c insoluble fiber might key contributors observed protective effect pubmed","probabilities":0.9799733,"Title":"The relationship between vegetable/fruit consumption and gallbladder/bile duct cancer: A population-based cohort study in Japan","Abstract":"Vegetable and fruit consumption may have a protective effect against several types of cancers. However, the effect on biliary cancers is unclear. We investigated the association of vegetable/fruit consumption with the risks of gallbladder cancer (GBC), intrahepatic bile duct cancer (IHBDC) and extrahepatic bile duct cancer (EHBDC) in a population-based prospective cohort study in Japan. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model, and the exposure level was categorized into quartiles, with the lowest group used as the reference. A total of 80,371 people aged 45 to 74 years were enrolled between 1995 and 1999, and followed up for 1,158,632 person-years until 2012, during which 133 GBC, 99 IHBDC, and 161 EHBDC cases were identified. Increased consumption of total vegetable and fruit was significantly associated with a decreased risk of EHBDC (HR = 0.49; 95% CI: 0.29-0.81 for the highest group; p trend = 0.005). From the analysis of relevant nutrients, significantly decreased risk of EHBDC was associated with folate and insoluble fiber (HR = 0.48, 0.53; 95% CI: 0.28-0.85, 0.31-0.88 for the highest group; p trend = 0.010, 0.023; respectively), and a significant trend of decreased EHBDC risk associated with vitamin C was observed (p trend = 0.029). No decreased risk of GBC and IHBDC was found. Our findings suggest that increased vegetable/fruit consumption may decrease a risk of EHBDC, and folate, vitamin C, and insoluble fiber might be key contributors to the observed protective effect.","Source":"PubMed","category":"HUMAN","training_data":"The relationship between vegetable/fruit consumption and gallbladder/bile duct cancer: A population-based cohort study in Japan Vegetable and fruit consumption may have a protective effect against several types of cancers. However, the effect on biliary cancers is unclear. We investigated the association of vegetable/fruit consumption with the risks of gallbladder cancer (GBC), intrahepatic bile duct cancer (IHBDC) and extrahepatic bile duct cancer (EHBDC) in a population-based prospective cohort study in Japan. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using the Cox proportional hazard model, and the exposure level was categorized into quartiles, with the lowest group used as the reference. A total of 80,371 people aged 45 to 74 years were enrolled between 1995 and 1999, and followed up for 1,158,632 person-years until 2012, during which 133 GBC, 99 IHBDC, and 161 EHBDC cases were identified. Increased consumption of total vegetable and fruit was significantly associated with a decreased risk of EHBDC (HR = 0.49; 95% CI: 0.29-0.81 for the highest group; p trend = 0.005). From the analysis of relevant nutrients, significantly decreased risk of EHBDC was associated with folate and insoluble fiber (HR = 0.48, 0.53; 95% CI: 0.28-0.85, 0.31-0.88 for the highest group; p trend = 0.010, 0.023; respectively), and a significant trend of decreased EHBDC risk associated with vitamin C was observed (p trend = 0.029). No decreased risk of GBC and IHBDC was found. Our findings suggest that increased vegetable/fruit consumption may decrease a risk of EHBDC, and folate, vitamin C, and insoluble fiber might be key contributors to the observed protective effect. PubMed","prediction_labels":"HUMAN"},{"cleaned":"roles liver fluke infection risk factor cholangiocarcinoma several factors known associated risk cholangiocarcinoma cca infection liver flukes opisthorchis viverrini clonorchis sinensis often singled leading risk factor east southeast asia review current knowledge biology life cycle pathogenesis o viverrini role carcinogenic parasite presented trends age specific incidence liver cancer khon kaen northeast thailand considered compared prevalence profiles o viverrini potential impacts liver fluke control program particularly mass drug administration mda public health education past recent drop incidence cca discussed relation primary prevention control fatal bile duct cancer pubmed","probabilities":0.9799733,"Title":"Roles of liver fluke infection as risk factor for cholangiocarcinoma","Abstract":"Several factors are known to be associated with risk of cholangiocarcinoma (CCA) and infection with the liver flukes, Opisthorchis viverrini and Clonorchis sinensis, has often been singled out as the leading risk factor in east and southeast Asia. In this review, current knowledge of their biology, life cycle, and pathogenesis of O. viverrini, and its role as a carcinogenic parasite are presented. The trends of age-specific incidence of liver cancer in Khon Kaen, northeast Thailand are considered and compared with the prevalence profiles of O. viverrini. Potential impacts of the liver fluke control program particularly by mass drug administration (MDA) and public health education in the past and a recent drop of incidence of CCA are discussed in relation to primary prevention and control of this fatal bile duct cancer.","Source":"PubMed","category":"HUMAN","training_data":"Roles of liver fluke infection as risk factor for cholangiocarcinoma Several factors are known to be associated with risk of cholangiocarcinoma (CCA) and infection with the liver flukes, Opisthorchis viverrini and Clonorchis sinensis, has often been singled out as the leading risk factor in east and southeast Asia. In this review, current knowledge of their biology, life cycle, and pathogenesis of O. viverrini, and its role as a carcinogenic parasite are presented. The trends of age-specific incidence of liver cancer in Khon Kaen, northeast Thailand are considered and compared with the prevalence profiles of O. viverrini. Potential impacts of the liver fluke control program particularly by mass drug administration (MDA) and public health education in the past and a recent drop of incidence of CCA are discussed in relation to primary prevention and control of this fatal bile duct cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"preoperative biliary drainage reduce postoperative liver failure patients undergoing major liver resection perihiliar colangiocarcinoma background preoperative portal vein embolization pve frequently used improve future liver remnant volume flrv reduce risk liver failure major liver resection objective paper aimed assess postoperative outcomes pve resection suspected perihilar cholangiocarcinoma phc international multicentric cohort methods patients undergoing resection suspected phc across 20 centers worldwide year 2000 included liver failure biliary leakage hemorrhage classified according respective international study group liver surgery criteria using propensity scoring two equal cohorts generated using matching parameters e age sex american society anesthesiologists classification jaundice type biliary drainage baseline flrv resection type portal vein resection results total 1667 patients treated suspected phc study period 298 patients underwent preoperative pve overall incidence liver failure 90 day mortality 27 18 respectively opposed 14 12 respectively patients without pve p 0 001 p 0 005 propensity score matching 98 patients enrolled cohort resulting similar baseline operative characteristics liver failure lower pve group 8 vs 36 p 0 001 biliary leakage 10 vs 35 p 0 01 intra abdominal abscesses 19 vs 34 p 0 01 90 day mortality 7 vs 18 p 0 03 conclusion pve major liver resection phc associated lower incidence liver failure biliary leakage abscess formation mortality results demonstrate importance pve integral component surgical treatment phc stn","probabilities":0.9799733,"Title":"Preoperative Biliary Drainage Reduce Postoperative Liver Failure On Patients Undergoing Major Liver Resection For Perihiliar Colangiocarcinoma","Abstract":"Background: Preoperative portal vein embolization (PVE) is frequently used to improve future liver remnant volume (FLRV) and to reduce the risk of liver failure after major liver resection. \r\n\r\n Objective: This paper aimed to assess postoperative outcomes after PVE and resection for suspected perihilar cholangiocarcinoma (PHC) in an international, multicentric cohort. \r\n\r\n Methods: Patients undergoing resection for suspected PHC across 20 centers worldwide, from the year 2000, were included. Liver failure, biliary leakage, and hemorrhage were classified according to the respective International Study Group of Liver Surgery criteria. Using propensity scoring, two equal cohorts were generated using matching parameters, i.e. age, sex, American Society of Anesthesiologists classification, jaundice, type of biliary drainage, baseline FLRV, resection type, and portal vein resection. \r\n\r\n Results: A total of 1667 patients were treated for suspected PHC during the study period. In 298 patients who underwent preoperative PVE, the overall incidence of liver failure and 90-day mortality was 27% and 18%, respectively, as opposed to 14% and 12%, respectively, in patients without PVE (p < 0.001 and p = 0.005). After propensity score matching, 98 patients were enrolled in each cohort, resulting in similar baseline and operative characteristics. Liver failure was lower in the PVE group (8% vs. 36%, p < 0.001), as was biliary leakage (10% vs. 35%, p < 0.01), intra-abdominal abscesses (19% vs. 34%, p = 0.01), and 90-day mortality (7% vs. 18%, p = 0.03). \r\n\r\n Conclusion: PVE before major liver resection for PHC is associated with a lower incidence of liver failure, biliary leakage, abscess formation, and mortality. These results demonstrate the importance of PVE as an integral component in the surgical treatment of PHC.","Source":"STN","category":"HUMAN","training_data":"Preoperative Biliary Drainage Reduce Postoperative Liver Failure On Patients Undergoing Major Liver Resection For Perihiliar Colangiocarcinoma Background: Preoperative portal vein embolization (PVE) is frequently used to improve future liver remnant volume (FLRV) and to reduce the risk of liver failure after major liver resection. \r\n\r\n Objective: This paper aimed to assess postoperative outcomes after PVE and resection for suspected perihilar cholangiocarcinoma (PHC) in an international, multicentric cohort. \r\n\r\n Methods: Patients undergoing resection for suspected PHC across 20 centers worldwide, from the year 2000, were included. Liver failure, biliary leakage, and hemorrhage were classified according to the respective International Study Group of Liver Surgery criteria. Using propensity scoring, two equal cohorts were generated using matching parameters, i.e. age, sex, American Society of Anesthesiologists classification, jaundice, type of biliary drainage, baseline FLRV, resection type, and portal vein resection. \r\n\r\n Results: A total of 1667 patients were treated for suspected PHC during the study period. In 298 patients who underwent preoperative PVE, the overall incidence of liver failure and 90-day mortality was 27% and 18%, respectively, as opposed to 14% and 12%, respectively, in patients without PVE (p < 0.001 and p = 0.005). After propensity score matching, 98 patients were enrolled in each cohort, resulting in similar baseline and operative characteristics. Liver failure was lower in the PVE group (8% vs. 36%, p < 0.001), as was biliary leakage (10% vs. 35%, p < 0.01), intra-abdominal abscesses (19% vs. 34%, p = 0.01), and 90-day mortality (7% vs. 18%, p = 0.03). \r\n\r\n Conclusion: PVE before major liver resection for PHC is associated with a lower incidence of liver failure, biliary leakage, abscess formation, and mortality. These results demonstrate the importance of PVE as an integral component in the surgical treatment of PHC. STN","prediction_labels":"HUMAN"},{"cleaned":"cancer risk surveillance primary sclerosing cholangitis primary sclerosing cholangitis psc chronic progressive disease characterized inflammatory fibrosing strictures biliary tree psc associated high lifetime risk hepatobiliary colorectal cancers nature carcinogenic process psc well established lack diagnostic methods early detection limited therapeutic options cholangiocarcinoma constitute major challenge current handling psc patients article reviews risk cancer development psc discusses surveillance strategies psc associated cancers pubmed","probabilities":0.9799733,"Title":"Cancer Risk and Surveillance in Primary Sclerosing Cholangitis","Abstract":"Primary sclerosing cholangitis (PSC) is a chronic, progressive disease characterized by inflammatory and fibrosing strictures of the biliary tree. PSC is associated with a high lifetime risk of hepatobiliary and colorectal cancers. The nature of the carcinogenic process in PSC is not well established. The lack of diagnostic methods for early detection and the limited therapeutic options for cholangiocarcinoma constitute a major challenge in the current handling of PSC patients. The article reviews the risk for cancer development in PSC and discusses surveillance strategies for PSC-associated cancers.","Source":"PubMed","category":"HUMAN","training_data":"Cancer Risk and Surveillance in Primary Sclerosing Cholangitis Primary sclerosing cholangitis (PSC) is a chronic, progressive disease characterized by inflammatory and fibrosing strictures of the biliary tree. PSC is associated with a high lifetime risk of hepatobiliary and colorectal cancers. The nature of the carcinogenic process in PSC is not well established. The lack of diagnostic methods for early detection and the limited therapeutic options for cholangiocarcinoma constitute a major challenge in the current handling of PSC patients. The article reviews the risk for cancer development in PSC and discusses surveillance strategies for PSC-associated cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"dna damage inflammation related carcinogenesis cancer stem cells infection chronic inflammation recognized important factors carcinogenesis inflammatory conditions reactive oxygen species ros reactive nitrogen species rns generated inflammatory epithelial cells result oxidative nitrative dna damage 8 oxo 7 8 dihydro 2 deoxyguanosine 8 oxodg 8 nitroguanine dna damage cause mutations implicated initiation promotion inflammation mediated carcinogenesis estimated various infectious agents carcinogenic humans iarc group 1 including parasites schistosoma haematobium sh opisthorchis viverrini ov viruses hepatitis c virus hcv human papillomavirus hpv epstein barr virus ebv bacterium helicobacter pylori hp sh ov hcv hpv ebv hp important risk factors bladder cancer cholangiocarcinoma hepatocellular carcinoma cervical cancer nasopharyngeal carcinoma gastric cancer respectively demonstrated 8 nitroguanine strongly formed via inducible nitric oxide synthase inos expression cancer sites patients moreover 8 nitroguanine formed oct3 4 positive stem cells sh associated bladder cancer tissues oct3 4 cd133 positive stem cells ov associated cholangiocarcinoma tissues therefore considered oxidative nitrative dna damage stem cells may play key role inflammation related carcinogenesis pubmed","probabilities":0.8684211,"Title":"DNA damage in inflammation-related carcinogenesis and cancer stem cells","Abstract":"Infection and chronic inflammation have been recognized as important factors for carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells and result in oxidative and nitrative DNA damage, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. The DNA damage can cause mutations and has been implicated in the initiation and/or promotion of inflammation-mediated carcinogenesis. It has been estimated that various infectious agents are carcinogenic to humans (IARC group 1), including parasites (Schistosoma haematobium (SH) and Opisthorchis viverrini (OV)), viruses (hepatitis C virus (HCV), human papillomavirus (HPV), and Epstein-Barr virus (EBV)), and bacterium Helicobacter pylori (HP). SH, OV, HCV, HPV, EBV, and HP are important risk factors for bladder cancer, cholangiocarcinoma, hepatocellular carcinoma, cervical cancer, nasopharyngeal carcinoma, and gastric cancer, respectively. We demonstrated that 8-nitroguanine was strongly formed via inducible nitric oxide synthase (iNOS) expression at these cancer sites of patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in SH-associated bladder cancer tissues and in Oct3/4- and CD133-positive stem cells in OV-associated cholangiocarcinoma tissues. Therefore, it is considered that oxidative and nitrative DNA damage in stem cells may play a key role in inflammation-related carcinogenesis.","Source":"PubMed","category":"HUMAN","training_data":"DNA damage in inflammation-related carcinogenesis and cancer stem cells Infection and chronic inflammation have been recognized as important factors for carcinogenesis. Under inflammatory conditions, reactive oxygen species (ROS) and reactive nitrogen species (RNS) are generated from inflammatory and epithelial cells and result in oxidative and nitrative DNA damage, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-nitroguanine. The DNA damage can cause mutations and has been implicated in the initiation and/or promotion of inflammation-mediated carcinogenesis. It has been estimated that various infectious agents are carcinogenic to humans (IARC group 1), including parasites (Schistosoma haematobium (SH) and Opisthorchis viverrini (OV)), viruses (hepatitis C virus (HCV), human papillomavirus (HPV), and Epstein-Barr virus (EBV)), and bacterium Helicobacter pylori (HP). SH, OV, HCV, HPV, EBV, and HP are important risk factors for bladder cancer, cholangiocarcinoma, hepatocellular carcinoma, cervical cancer, nasopharyngeal carcinoma, and gastric cancer, respectively. We demonstrated that 8-nitroguanine was strongly formed via inducible nitric oxide synthase (iNOS) expression at these cancer sites of patients. Moreover, 8-nitroguanine was formed in Oct3/4-positive stem cells in SH-associated bladder cancer tissues and in Oct3/4- and CD133-positive stem cells in OV-associated cholangiocarcinoma tissues. Therefore, it is considered that oxidative and nitrative DNA damage in stem cells may play a key role in inflammation-related carcinogenesis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extra intestinal malignancies inflammatory bowel diseases update emphasis mdct mr imaging features inflammatory bowel diseases ibd associated increased risk gastrointestinal cancers specifically sites affected chronic inflammation however patients ibd also increased risk developing variety extra intestinal cancers regard hepatobiliary cancers cholangiocarcinoma frequently observed ibd patients high prevalence primary sclerosing cholangitis considered favoring condition extra intestinal lymphomas mostly non hodgkin lymphomas skin cancers also observed increased incidence ibd patients comparison patients without ibd review provides update demographics risk factors clinical features extra intestinal malignancies including cholangiocarcinoma hepatocellular carcinoma lymphoma occur patients ibd along special emphasis multidetector row computed tomography magnetic resonance imaging features uncommon conditions pubmed","probabilities":0.9799733,"Title":"Extra-intestinal malignancies in inflammatory bowel diseases: An update with emphasis on MDCT and MR imaging features","Abstract":"Inflammatory bowel diseases (IBD) are associated with an increased risk of gastrointestinal cancers and more specifically in sites affected by chronic inflammation. However, patients with IBD have also an increased risk for developing a variety of extra-intestinal cancers. In this regard, hepatobiliary cancers, such as cholangiocarcinoma, are more frequently observed in IBD patients because of a high prevalence of primary sclerosing cholangitis, which is considered as a favoring condition. Extra-intestinal lymphomas, mostly non-Hodgkin lymphomas, and skin cancers are also observed with an increased incidence in IBD patients by comparison with that in patients without IBD. This review provides an update on demographics, risk factors and clinical features of extra-intestinal malignancies, including cholangiocarcinoma, hepatocellular carcinoma and lymphoma, that occur in patients with IBD along with a special emphasis on the multidetector row computed tomography and magnetic resonance imaging features of these uncommon conditions.","Source":"PubMed","category":"HUMAN","training_data":"Extra-intestinal malignancies in inflammatory bowel diseases: An update with emphasis on MDCT and MR imaging features Inflammatory bowel diseases (IBD) are associated with an increased risk of gastrointestinal cancers and more specifically in sites affected by chronic inflammation. However, patients with IBD have also an increased risk for developing a variety of extra-intestinal cancers. In this regard, hepatobiliary cancers, such as cholangiocarcinoma, are more frequently observed in IBD patients because of a high prevalence of primary sclerosing cholangitis, which is considered as a favoring condition. Extra-intestinal lymphomas, mostly non-Hodgkin lymphomas, and skin cancers are also observed with an increased incidence in IBD patients by comparison with that in patients without IBD. This review provides an update on demographics, risk factors and clinical features of extra-intestinal malignancies, including cholangiocarcinoma, hepatocellular carcinoma and lymphoma, that occur in patients with IBD along with a special emphasis on the multidetector row computed tomography and magnetic resonance imaging features of these uncommon conditions. PubMed","prediction_labels":"HUMAN"},{"cleaned":"port site resection improve survival incidental gallbladder cancer afc gbc 2009 study group background incidental gallbladder cancer gbc frequently discovered specimen cholecystectomy benign disease performed objective present study assess management incidental gbc patients french registry methods data patients gbc treated 1998 2008 retrospectively collated french multicenter database results registry contained 218 patients incidental gbc 67 men 151 women median age 64 years age range 31 88 one hundred forty eight 68 patients underwent re resection median time interval 48 days range 2 245 common complete procedure 66 cases 4b 5 segmentectomy lymphadenectomy bile duct resection port site excision performed 54 patients mortality morbidity rates 3 37 respectively resection common bile duct 43 increased postoperative complications 60 vs 23 p 0 0001 local residual tumor found 83 56 patients significantly correlated stage influenced long term survival r0 obtained 143 97 patients port site invasion histologically confirmed one patient 1 8 median follow period 34 months 1 3 5 year survival rates 148 patients re resection 76 54 41 respectively re resection significantly increased survival patients t2 p 0 0001 t3 p 0 04 disease resection common bile duct increased neither r0 resection overall survival p 0 06 conclusion study validates concept re resection t2 t3 gbc bile duct resection increases postoperative morbidity improve survival currently modification surgical management incidental gbc minor liver resection common bile duct resection stn","probabilities":0.9799733,"Title":"Port Site Resection Does Not Improve Survival In Incidental Gallbladder Cancer By The Afc-Gbc-2009 Study Group","Abstract":"Background: Incidental gallbladder cancer (GBC) is frequently discovered on the specimen when cholecystectomy for a benign disease is performed. The objective of the present study was to assess the management of incidental GBC patients in a French registry. \r\n\r\n Methods: Data on patients with GBC treated between 1998 and 2008 were retrospectively collated in a French, multicenter database. \r\n\r\n Results: The registry contained 218 patients with incidental GBC (67 men and 151 women; median age = 64 years; age range = 31-88). One hundred forty-eight (68%) patients underwent re-resection after a median time interval of 48 days (range = 2-245). The most common complete procedure (66% of cases) was 4b + 5 segmentectomy with lymphadenectomy but not bile duct resection. Port-site excision was performed in 54 patients. The mortality and morbidity rates were 3 and 37%, respectively. Resection of the common bile duct (43%) increased postoperative complications (60 vs. 23%, p = 0.0001). Local residual tumor was found in 83 (56%) patients; it was significantly correlated with the T stage and influenced long-term survival. R0 was obtained in 143 (97%) patients and port-site invasion was histologically confirmed in one patient (1.8%). After a median follow-up period of 34 months, the 1-, 3-, and 5-year survival rates for the 148 patients with re-resection were 76, 54, and 41%, respectively. Re-resection significantly increased survival in patients with T2 (p = 0.0001) and T3 (p = 0.04) disease. Resection of the common bile duct increased neither R0 resection nor overall survival (p = 0.06). \r\n\r\n Conclusion: This study validates the concept of re-resection in T2 and T3 GBC. Bile duct resection increases postoperative morbidity but does not improve survival. There is currently a modification in the surgical management of incidental GBC, with minor liver resection and no common bile duct resection.","Source":"STN","category":"HUMAN","training_data":"Port Site Resection Does Not Improve Survival In Incidental Gallbladder Cancer By The Afc-Gbc-2009 Study Group Background: Incidental gallbladder cancer (GBC) is frequently discovered on the specimen when cholecystectomy for a benign disease is performed. The objective of the present study was to assess the management of incidental GBC patients in a French registry. \r\n\r\n Methods: Data on patients with GBC treated between 1998 and 2008 were retrospectively collated in a French, multicenter database. \r\n\r\n Results: The registry contained 218 patients with incidental GBC (67 men and 151 women; median age = 64 years; age range = 31-88). One hundred forty-eight (68%) patients underwent re-resection after a median time interval of 48 days (range = 2-245). The most common complete procedure (66% of cases) was 4b + 5 segmentectomy with lymphadenectomy but not bile duct resection. Port-site excision was performed in 54 patients. The mortality and morbidity rates were 3 and 37%, respectively. Resection of the common bile duct (43%) increased postoperative complications (60 vs. 23%, p = 0.0001). Local residual tumor was found in 83 (56%) patients; it was significantly correlated with the T stage and influenced long-term survival. R0 was obtained in 143 (97%) patients and port-site invasion was histologically confirmed in one patient (1.8%). After a median follow-up period of 34 months, the 1-, 3-, and 5-year survival rates for the 148 patients with re-resection were 76, 54, and 41%, respectively. Re-resection significantly increased survival in patients with T2 (p = 0.0001) and T3 (p = 0.04) disease. Resection of the common bile duct increased neither R0 resection nor overall survival (p = 0.06). \r\n\r\n Conclusion: This study validates the concept of re-resection in T2 and T3 GBC. Bile duct resection increases postoperative morbidity but does not improve survival. There is currently a modification in the surgical management of incidental GBC, with minor liver resection and no common bile duct resection. STN","prediction_labels":"HUMAN"},{"cleaned":"retrospective analysis gemcitabine nab paclitaxel treatment metastatic cholangiocarcinoma background cholangiocarcinoma cca progressively fatal disease annual incidence 1 2 cases per 100 000 people usa complete surgical resection curative option cca however majority patients pts advanced disease diagnosis undergoing resection often develop local distant recurrence gemcitabine cisplatin remains standard chemotherapeutic regimen advanced cca alternative improved therapies critically needed gemcitabine nab paclitaxel ga regimen become standard therapy advanced pancreatic cancer pdac given morphologic histologic similarities pdac cca regimen used advanced cca data exists regarding efficacy disease goal study evaluate mayo clinic experience ga treatment metastatic cca methods retrospectively analyzed records adult pts mayo clinic metastatic cholangiocarcinoma received least 2 cycles ga aims assess progression free survival pfs overall survival os disease response results analyzed 9 pts 3 male 6 female median age diagnosis 50 years range 41 64 six pts metastatic disease diagnosis 3 underwent surgery subsequent distant disease recurrence pts received median 2 lines range 0 5 systemic therapy prior receiving ga median 2 cycles range 2 15 ga time analysis 4 9 pts 44 died median os initiation ga 7 3 months 95 ci 1 7 12 9 median pfs initiation ga 4 7 months 95 ci 0 48 8 9 best overall responses using recist criteria partial response 1 11 stable disease 5 55 disease progression 3 33 pts one pt remained therapy 14 9 months initiating ga conclusions study combination gemcitabine nab paclitaxel demonstrated similar os pfs systemic therapies best knowledge first report regimen cca ongoing prospective trials currently evaluating regimen advanced cca google scholar","probabilities":0.9799733,"Title":"A Retrospective Analysis Of Gemcitabine And Nab-Paclitaxel For The Treatment Of Metastatic Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinoma (CCA) is a progressively fatal disease with an annual incidence of 1-2 cases per 100,000 people in the USA. Complete surgical resection is the only curative option for CCA. However, the majority of patients (pts) have advanced disease at diagnosis, and those undergoing resection often develop local or distant recurrence. Gemcitabine and Cisplatin remains the only standard chemotherapeutic regimen for advanced CCA. Alternative and improved therapies are critically needed. Gemcitabine/nab-Paclitaxel (GA) is a regimen that has become standard therapy in advanced pancreatic cancer (PDAC). Given the morphologic and histologic similarities between PDAC and CCA, this regimen has been used in advanced CCA, but no data exists regarding its efficacy in this disease. The goal of our study is to evaluate the Mayo Clinic experience with GA for the treatment of metastatic CCA. Methods: We retrospectively analyzed records from adult pts at Mayo Clinic with metastatic cholangiocarcinoma who received at least 2 cycles of GA. Our aims were to assess the progression-free survival (PFS), overall survival (OS) and disease response. Results: We analyzed 9 pts, 3 male and 6 female. The median age at diagnosis was 50 years (range 41-64). Six pts had metastatic disease at diagnosis while 3 underwent surgery with subsequent distant disease recurrence. Pts received a median of 2 lines (range 0-5) of systemic therapy prior to receiving GA, and a median of 2 cycles (range 2-15) of GA. At the time of our analysis, 4 of the 9 pts (44%) had died. The median OS from initiation of GA was 7.3 months (95% CI 1.7- 12.9) and median PFS from initiation of GA was 4.7 months (95% CI 0.48-8.9). The best overall responses using RECIST criteria were: partial response in 1 (11%), stable disease in 5 (55%) and disease progression in 3 (33%) pts. One pt remained on therapy 14.9 months after initiating GA. Conclusions: In our study, the combination of gemcitabine and nab-paclitaxel has demonstrated similar OS and PFS as other systemic therapies. To the best of our knowledge, this is the first report of this regimen in CCA. Ongoing, prospective trials are currently evaluating this regimen in advanced CCA.","Source":"Google Scholar","category":"HUMAN","training_data":"A Retrospective Analysis Of Gemcitabine And Nab-Paclitaxel For The Treatment Of Metastatic Cholangiocarcinoma Background: Cholangiocarcinoma (CCA) is a progressively fatal disease with an annual incidence of 1-2 cases per 100,000 people in the USA. Complete surgical resection is the only curative option for CCA. However, the majority of patients (pts) have advanced disease at diagnosis, and those undergoing resection often develop local or distant recurrence. Gemcitabine and Cisplatin remains the only standard chemotherapeutic regimen for advanced CCA. Alternative and improved therapies are critically needed. Gemcitabine/nab-Paclitaxel (GA) is a regimen that has become standard therapy in advanced pancreatic cancer (PDAC). Given the morphologic and histologic similarities between PDAC and CCA, this regimen has been used in advanced CCA, but no data exists regarding its efficacy in this disease. The goal of our study is to evaluate the Mayo Clinic experience with GA for the treatment of metastatic CCA. Methods: We retrospectively analyzed records from adult pts at Mayo Clinic with metastatic cholangiocarcinoma who received at least 2 cycles of GA. Our aims were to assess the progression-free survival (PFS), overall survival (OS) and disease response. Results: We analyzed 9 pts, 3 male and 6 female. The median age at diagnosis was 50 years (range 41-64). Six pts had metastatic disease at diagnosis while 3 underwent surgery with subsequent distant disease recurrence. Pts received a median of 2 lines (range 0-5) of systemic therapy prior to receiving GA, and a median of 2 cycles (range 2-15) of GA. At the time of our analysis, 4 of the 9 pts (44%) had died. The median OS from initiation of GA was 7.3 months (95% CI 1.7- 12.9) and median PFS from initiation of GA was 4.7 months (95% CI 0.48-8.9). The best overall responses using RECIST criteria were: partial response in 1 (11%), stable disease in 5 (55%) and disease progression in 3 (33%) pts. One pt remained on therapy 14.9 months after initiating GA. Conclusions: In our study, the combination of gemcitabine and nab-paclitaxel has demonstrated similar OS and PFS as other systemic therapies. To the best of our knowledge, this is the first report of this regimen in CCA. Ongoing, prospective trials are currently evaluating this regimen in advanced CCA. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"transarterial chemoembolization treatment patients unresectable cholangiocarcinoma results prognostic factors governing treatment success aim study evaluate effectiveness transarterial chemoembolization tace four chemotherapeutic protocols terms local tumor control survival patients unresectable cholangiocarcinoma ccc identify prognostic factors governing treatment success single centre study 115 patients mean ages 60 4 years unresectable ccc repeatedly treated tace total 819 chemoembolization sessions performed 4 week intervals mean 7 1 range 3 30 sessions per patient chemotherapeutic used mitomycin c 20 9 patients gemcitabine 7 mitomycin c gemcitabine 47 combination gemcitabine mitomycin c cisplatin 25 1 local tumor response evaluated mri according recist survival data calculated according kaplan meier method prognostic factors patient survival evaluated using log rank test local tumor controls partial response 8 7 stable disease 57 4 progressive disease 33 9 patients median mean survival times start tace 13 20 8 months survival rate start tace 52 1 year 29 2 years 10 3 years initial tumor response high tumor vascularity child pugh class statistically significant factors patient survival statistically significant difference patients treated different chemotherapy protocols noted conclusion tace palliative safe treatment option patients unresectable ccc child pugh class b tumor hypovascularity initially progressive disease poor prognostic factors patient survival stn","probabilities":0.9799733,"Title":"Transarterial Chemoembolization In The Treatment Of Patients With Unresectable Cholangiocarcinoma: Results And Prognostic Factors Governing Treatment Success","Abstract":"The aim of the study was to evaluate the effectiveness of transarterial chemoembolization (TACE) with four chemotherapeutic protocols in terms of local tumor control and survival of patients with unresectable cholangiocarcinoma (CCC) and to identify the prognostic factors governing treatment success. In the single-centre study, 115 patients (mean ages = 60.4 years) with unresectable CCC were repeatedly treated with TACE. In total, 819 chemoembolization sessions were performed in 4 week intervals with a mean of 7.1 (range, 3-30) sessions per patient. The chemotherapeutic used was Mitomycin C only in 20.9% of patients, Gemcitabine only in 7%, Mitomycin C with Gemcitabine in 47% and combination of Gemcitabine, Mitomycin C and Cisplatin in 25.1%. Local tumor response was evaluated by MRI according to RECIST. Survival data were calculated according to the Kaplan-Meier method. Prognostic factors for patient's survival were evaluated using log-rank-test. The local tumor controls were: partial response 8.7%, stable disease 57.4% and progressive disease 33.9% of patients. The median and mean survival times from the start of TACE were 13 and 20.8 months. Survival rate from the start of TACE was 52% after 1-year, 29% after 2-years and 10% after 3-years. Initial tumor response, high tumor vascularity and Child-Pugh class A were statistically significant factors for patient's survival. No statistically significant difference between patients treated with different chemotherapy protocols was noted. In conclusion, TACE is a palliative and safe treatment option for patients with unresectable CCC. Child Pugh class B, tumor hypovascularity and initially progressive disease were poor prognostic factors for patient survival.","Source":"STN","category":"HUMAN","training_data":"Transarterial Chemoembolization In The Treatment Of Patients With Unresectable Cholangiocarcinoma: Results And Prognostic Factors Governing Treatment Success The aim of the study was to evaluate the effectiveness of transarterial chemoembolization (TACE) with four chemotherapeutic protocols in terms of local tumor control and survival of patients with unresectable cholangiocarcinoma (CCC) and to identify the prognostic factors governing treatment success. In the single-centre study, 115 patients (mean ages = 60.4 years) with unresectable CCC were repeatedly treated with TACE. In total, 819 chemoembolization sessions were performed in 4 week intervals with a mean of 7.1 (range, 3-30) sessions per patient. The chemotherapeutic used was Mitomycin C only in 20.9% of patients, Gemcitabine only in 7%, Mitomycin C with Gemcitabine in 47% and combination of Gemcitabine, Mitomycin C and Cisplatin in 25.1%. Local tumor response was evaluated by MRI according to RECIST. Survival data were calculated according to the Kaplan-Meier method. Prognostic factors for patient's survival were evaluated using log-rank-test. The local tumor controls were: partial response 8.7%, stable disease 57.4% and progressive disease 33.9% of patients. The median and mean survival times from the start of TACE were 13 and 20.8 months. Survival rate from the start of TACE was 52% after 1-year, 29% after 2-years and 10% after 3-years. Initial tumor response, high tumor vascularity and Child-Pugh class A were statistically significant factors for patient's survival. No statistically significant difference between patients treated with different chemotherapy protocols was noted. In conclusion, TACE is a palliative and safe treatment option for patients with unresectable CCC. Child Pugh class B, tumor hypovascularity and initially progressive disease were poor prognostic factors for patient survival. STN","prediction_labels":"HUMAN"},{"cleaned":"epidemiology prevalence gallbladder cancer united states population based study background aim tyrosine kinase inhibitors tkis first line treatment drugs sorafenib sor lenvatinib len well regorafenib reg used second line treatment developed treatment patients unresectable hepatocellular carcinoma u hcc len shown effective first line therapy also second third line option japan study investigated clinical factors associated prognosis improvement patients underwent tki sequential therapy google scholar","probabilities":0.9799733,"Title":"Epidemiology And Prevalence Of Gallbladder Cancer In The United States: A Population-Based Study","Abstract":"Background/Aim: Tyrosine kinase inhibitors (TKIs), such as the first-line treatment drugs \nsorafenib (SOR) and lenvatinib (LEN), as well as regorafenib (REG) used for second-line \ntreatment, have been developed for treatment of patients with unresectable hepatocellular \ncarcinoma (u-HCC). LEN has been shown to be effective in not only first-line therapy, but \nalso as a second-and third-line option in Japan. This study investigated clinical factors \nassociated with prognosis improvement of in patients who underwent TKI sequential therapy …","Source":"Google Scholar","category":"HUMAN","training_data":"Epidemiology And Prevalence Of Gallbladder Cancer In The United States: A Population-Based Study Background/Aim: Tyrosine kinase inhibitors (TKIs), such as the first-line treatment drugs \nsorafenib (SOR) and lenvatinib (LEN), as well as regorafenib (REG) used for second-line \ntreatment, have been developed for treatment of patients with unresectable hepatocellular \ncarcinoma (u-HCC). LEN has been shown to be effective in not only first-line therapy, but \nalso as a second-and third-line option in Japan. This study investigated clinical factors \nassociated with prognosis improvement of in patients who underwent TKI sequential therapy … Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cea ca19 9 independent prognostic factor patients undergoing resection cholangiocarcinoma cholangiocarcinoma cca represents rare form primary liver cancer increasing incidence dismal prognosis surgical treatment remained potentially curative treatment option remains unclear patients benefit liver surgery highlighting need new preoperative stratification strategies clinical routine ca19 9 represents widely used tumor marker cca patients however data prognostic value ca19 9 cca patients limited often inconclusive mostly due small cohort sizes investigated prognostic value ca19 9 comparison standard laboratory markers large cohort cca patients underwent tumor resection note ca19 9 cea able discriminate cca healthy controls cea showed higher accuracy differentiation cca patients primary sclerosing cholangitis psc compared ca19 9 furthermore patients elevated levels c reactive protein crp ca19 9 cea showed significantly impaired survival kaplan meier curve analysis surprisingly cea ca19 9 represented independent predictor survival multivariate cox regression analysis data suggest cea might help identify cca patients unfavourable prognosis tumor resection pubmed","probabilities":0.9799733,"Title":"CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) represents a rare form of primary liver cancer with increasing incidence but dismal prognosis. Surgical treatment has remained the only potentially curative treatment option, but it remains unclear which patients benefit most from liver surgery, highlighting the need for new preoperative stratification strategies. In clinical routine, CA19-9 represents the most widely used tumor marker in CCA patients. However, data on the prognostic value of CA19-9 in CCA patients are limited and often inconclusive, mostly due to small cohort sizes. Here, we investigated the prognostic value of CA19-9 in comparison with other standard laboratory markers in a large cohort of CCA patients that underwent tumor resection. Of note, while CA19-9 and CEA were able to discriminate between CCA and healthy controls, CEA showed a higher accuracy for the differentiation between CCA and patients with primary sclerosing cholangitis (PSC) compared to CA19-9. Furthermore, patients with elevated levels of C-reactive protein (CRP), CA19-9 or CEA showed a significantly impaired survival in Kaplan-Meier curve analysis, but surprisingly, only CEA but not CA19-9 represented an independent predictor of survival in multivariate Cox-regression analysis. Our data suggest that CEA might help to identify CCA patients with an unfavourable prognosis after tumor resection.","Source":"PubMed","category":"HUMAN","training_data":"CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma Cholangiocarcinoma (CCA) represents a rare form of primary liver cancer with increasing incidence but dismal prognosis. Surgical treatment has remained the only potentially curative treatment option, but it remains unclear which patients benefit most from liver surgery, highlighting the need for new preoperative stratification strategies. In clinical routine, CA19-9 represents the most widely used tumor marker in CCA patients. However, data on the prognostic value of CA19-9 in CCA patients are limited and often inconclusive, mostly due to small cohort sizes. Here, we investigated the prognostic value of CA19-9 in comparison with other standard laboratory markers in a large cohort of CCA patients that underwent tumor resection. Of note, while CA19-9 and CEA were able to discriminate between CCA and healthy controls, CEA showed a higher accuracy for the differentiation between CCA and patients with primary sclerosing cholangitis (PSC) compared to CA19-9. Furthermore, patients with elevated levels of C-reactive protein (CRP), CA19-9 or CEA showed a significantly impaired survival in Kaplan-Meier curve analysis, but surprisingly, only CEA but not CA19-9 represented an independent predictor of survival in multivariate Cox-regression analysis. Our data suggest that CEA might help to identify CCA patients with an unfavourable prognosis after tumor resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"mucins old new promising factors hepatobiliary carcinogenesis mucins large o glycoproteins high carbohydrate content marked diversity apoprotein oligosaccharide moieties three mucin types trans membrane e g muc1 muc4 muc16 secreted gel forming e g muc2 muc5ac muc6 soluble non gel forming e g muc7 muc8 muc9 muc20 critical maintaining cellular functions particularly epithelial surfaces aberrant expression altered subcellular localization factor tumour growth apoptosis induced oxidative stress several anti cancer agents abnormal expression mucins observed human carcinomas arise various gastrointestinal organs widely believed hepatocellular carcinoma hcc produce mucins whereas cholangiocarcinoma cc combined hcc cc may produce glycoproteins however growing number reports shows mucins produced hcc cells exhibit yet undergo morphological differentiation biliary phenotypes evaluation mucin expression levels precursors early lesions cc well types primary liver cancer plc conducted vitro vivo models allowed discover mechanisms action well participation important signalling pathways liver cystogenesis carcinogenesis analysis mucin expression plc basic research clinical value mucins may act oncogenes tumour promoting e g muc1 muc13 tumour suppressing factors e g muc15 given role promoting plc progression classic muc1 muc2 muc4 muc5ac muc6 currently tested mucins e g muc13 muc15 muc16 proposed important diagnostic prognostic markers purpose review summarize update role classic currently tested mucins pathogenesis plc explaining mechanisms action hcc carcinogenesis also focuses determination diagnostic prognostic role glycoproteins plc especially focusing hcc cc hepatic tumours without biliary differentiation pubmed","probabilities":0.8684211,"Title":"Mucins: the Old, the New and the Promising Factors in Hepatobiliary Carcinogenesis","Abstract":"Mucins are large O-glycoproteins with high carbohydrate content and marked diversity in both the apoprotein and the oligosaccharide moieties. All three mucin types, trans-membrane (e.g., MUC1, MUC4, MUC16), secreted (gel-forming) (e.g., MUC2, MUC5AC, MUC6) and soluble (non-gel-forming) (e.g., MUC7, MUC8, MUC9, MUC20), are critical in maintaining cellular functions, particularly those of epithelial surfaces. Their aberrant expression and/or altered subcellular localization is a factor of tumour growth and apoptosis induced by oxidative stress and several anti-cancer agents. Abnormal expression of mucins was observed in human carcinomas that arise in various gastrointestinal organs. It was widely believed that hepatocellular carcinoma (HCC) does not produce mucins, whereas cholangiocarcinoma (CC) or combined HCC-CC may produce these glycoproteins. However, a growing number of reports shows that mucins can be produced by HCC cells that do not exhibit or are yet to undergo, morphological differentiation to biliary phenotypes. Evaluation of mucin expression levels in precursors and early lesions of CC, as well as other types of primary liver cancer (PLC), conducted in in vitro and in vivo models, allowed to discover the mechanisms of their action, as well as their participation in the most important signalling pathways of liver cystogenesis and carcinogenesis. Analysis of mucin expression in PLC has both basic research and clinical value. Mucins may act as oncogenes and tumour-promoting (e.g., MUC1, MUC13), and/or tumour-suppressing factors (e.g., MUC15). Given their role in promoting PLC progression, both classic (MUC1, MUC2, MUC4, MUC5AC, MUC6) and currently tested mucins (e.g., MUC13, MUC15, MUC16) have been proposed to be important diagnostic and prognostic markers. The purpose of this review was to summarize and update the role of classic and currently tested mucins in pathogenesis of PLC, with explaining the mechanisms of their action in HCC carcinogenesis. It also focuses on determination of the diagnostic and prognostic role of these glycoproteins in PLC, especially focusing on HCC, CC and other hepatic tumours with- and without biliary differentiation.","Source":"PubMed","category":"ANIMAL","training_data":"Mucins: the Old, the New and the Promising Factors in Hepatobiliary Carcinogenesis Mucins are large O-glycoproteins with high carbohydrate content and marked diversity in both the apoprotein and the oligosaccharide moieties. All three mucin types, trans-membrane (e.g., MUC1, MUC4, MUC16), secreted (gel-forming) (e.g., MUC2, MUC5AC, MUC6) and soluble (non-gel-forming) (e.g., MUC7, MUC8, MUC9, MUC20), are critical in maintaining cellular functions, particularly those of epithelial surfaces. Their aberrant expression and/or altered subcellular localization is a factor of tumour growth and apoptosis induced by oxidative stress and several anti-cancer agents. Abnormal expression of mucins was observed in human carcinomas that arise in various gastrointestinal organs. It was widely believed that hepatocellular carcinoma (HCC) does not produce mucins, whereas cholangiocarcinoma (CC) or combined HCC-CC may produce these glycoproteins. However, a growing number of reports shows that mucins can be produced by HCC cells that do not exhibit or are yet to undergo, morphological differentiation to biliary phenotypes. Evaluation of mucin expression levels in precursors and early lesions of CC, as well as other types of primary liver cancer (PLC), conducted in in vitro and in vivo models, allowed to discover the mechanisms of their action, as well as their participation in the most important signalling pathways of liver cystogenesis and carcinogenesis. Analysis of mucin expression in PLC has both basic research and clinical value. Mucins may act as oncogenes and tumour-promoting (e.g., MUC1, MUC13), and/or tumour-suppressing factors (e.g., MUC15). Given their role in promoting PLC progression, both classic (MUC1, MUC2, MUC4, MUC5AC, MUC6) and currently tested mucins (e.g., MUC13, MUC15, MUC16) have been proposed to be important diagnostic and prognostic markers. The purpose of this review was to summarize and update the role of classic and currently tested mucins in pathogenesis of PLC, with explaining the mechanisms of their action in HCC carcinogenesis. It also focuses on determination of the diagnostic and prognostic role of these glycoproteins in PLC, especially focusing on HCC, CC and other hepatic tumours with- and without biliary differentiation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"aggressive surgery locally advanced gallbladder cancer obstructive jaundice result prospective study objective aim study clarify clinical impact departmental policy advanced gallbladder cancer gbc even obstructive jaundice methods obstructive jaundice defined serum bil 2 0 mg dl 1998 2008 112 patients gbc scheduled surgical resection curative intent thirty six patients converted palliative surgery exploration alone advanced disease excluding pathological t1 uicc patients n 11 remaining 65 patients divided 2 groups jaundiced group n 37 non jaundiced group n 28 surgical procedures conducted based departmental guidelines concerning type infiltration gbc results bile duct resection major hepatectomy performed frequently patients jaundice although patients jaundiced group advanced disease 5 year overall survival rates patients without jaundice 27 vs 31 p 0 742 statistically significant conclusions aggressive surgery might improve long term survival patients locally advanced gbc even condition obstructive jaundice distant metastasis pubmed","probabilities":0.9799733,"Title":"Aggressive Surgery for Locally Advanced Gallbladder Cancer with Obstructive Jaundice: Result of a Prospective Study","Abstract":"OBJECTIVE: The aim of this study was to clarify the clinical impact of our departmental policy for advanced gallbladder cancer (GBC) even with obstructive jaundice. METHODS: Obstructive jaundice was defined as serum T-bil ≥2.0 mg/dl. Between 1998 and 2008, 112 patients with GBC were scheduled for surgical resection with curative intent. Thirty-six patients were converted to palliative surgery or exploration alone because of advanced disease. After excluding pathological T1 (UICC) patients (n = 11), the remaining 65 patients were divided into 2 groups; jaundiced group (n = 37) and non-jaundiced group (n = 28). Surgical procedures were conducted based on our departmental guidelines concerning each type of infiltration of GBC. RESULTS: Bile duct resection and major hepatectomy were performed more frequently in patients with jaundice. Although patients in jaundiced group had more advanced disease, 5-year overall survival rates of the patients with or without jaundice were 27 vs. 31% (p = 0.742), which was not statistically significant. CONCLUSIONS: Aggressive surgery might improve long-term survival in patients with locally advanced GBC even in the condition of obstructive jaundice with no distant metastasis.","Source":"PubMed","category":"HUMAN","training_data":"Aggressive Surgery for Locally Advanced Gallbladder Cancer with Obstructive Jaundice: Result of a Prospective Study OBJECTIVE: The aim of this study was to clarify the clinical impact of our departmental policy for advanced gallbladder cancer (GBC) even with obstructive jaundice. METHODS: Obstructive jaundice was defined as serum T-bil ≥2.0 mg/dl. Between 1998 and 2008, 112 patients with GBC were scheduled for surgical resection with curative intent. Thirty-six patients were converted to palliative surgery or exploration alone because of advanced disease. After excluding pathological T1 (UICC) patients (n = 11), the remaining 65 patients were divided into 2 groups; jaundiced group (n = 37) and non-jaundiced group (n = 28). Surgical procedures were conducted based on our departmental guidelines concerning each type of infiltration of GBC. RESULTS: Bile duct resection and major hepatectomy were performed more frequently in patients with jaundice. Although patients in jaundiced group had more advanced disease, 5-year overall survival rates of the patients with or without jaundice were 27 vs. 31% (p = 0.742), which was not statistically significant. CONCLUSIONS: Aggressive surgery might improve long-term survival in patients with locally advanced GBC even in the condition of obstructive jaundice with no distant metastasis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical outcomes minor hepatectomy locally advanced gallbladder carcinoma background aims study aimed evaluate whether wedge resection s4bs5 resection beneficial hepatectomy procedure patients locally advanced gallbladder carcinoma methodology retrospective analysis 70 patients underwent either wedge resection n 58 s4bs5 resection n 12 locally advanced gallbladder carcinoma without clinically evident liver metastases conducted clinicopathological characteristics histological features hepatic invasion surgical outcomes analyzed results sixteen patients tumors hepatic invasion 16 patients hepatic invasion 6 direct liver invasion alone 10 portal tract invasion featuring intrahepatic stromal invasion n 5 intrahepatic lymphatic invasion n 4 intrahepatic venous invasion n l hepatectomy procedure significantly associated survival resection p 0 518 patients underwent wedge resection showed overall cumulative 3 year survival rate 74 compared 60 patients underwent s4bs5 resection cox proportional hazard regression analysis revealed pt classification p 0 001 pm classification p 0 001 resection extrahepatic bile duct p 0 048 independently significant factors associated survival resection conclusions hepatectomy procedure may significantly affect surgical outcomes patients gallbladder carcinoma partial hepatectomy involving gallbladder bed critical due possible tumor cells pubmed","probabilities":0.9799733,"Title":"Surgical outcomes of minor hepatectomy for locally advanced gallbladder carcinoma","Abstract":"BACKGROUND/AIMS: This study aimed to evaluate whether wedge resection or S4bS5 resection was the more beneficial hepatectomy procedure for patients with locally advanced gallbladder carcinoma. METHODOLOGY: A retrospective analysis of 70 patients who underwent either wedge resection (n=58) or S4bS5 resection (n=12) for locally advanced gallbladder carcinoma without clinically evident liver metastases was conducted. Clinicopathological characteristics, histological features of hepatic invasion and surgical outcomes were analyzed. RESULTS: Sixteen patients had tumors with hepatic invasion. Of the 16 patients with hepatic invasion, 6 had direct liver invasion alone and 10 had portal tract invasion featuring intrahepatic stromal invasion (n=5), intrahepatic lymphatic invasion (n=4) and intrahepatic venous invasion (n=l). The hepatectomy procedure was not significantly associated with survival after resection (p=0.518) as patients who underwent wedge resection showed an overall cumulative 3-year survival rate of 74% compared with 60% for patients who underwent S4bS5 resection. The Cox proportional hazard regression analysis revealed that pT classification (p<0.001), pM classification (p=0.001) and resection of the extrahepatic bile duct (p=0.048) were independently significant factors associated with survival after resection. CONCLUSIONS: Hepatectomy procedure may not significantly affect surgical outcomes in patients with gallbladder carcinoma. Partial hepatectomy involving the gallbladder bed is critical due to possible tumor cells.","Source":"PubMed","category":"HUMAN","training_data":"Surgical outcomes of minor hepatectomy for locally advanced gallbladder carcinoma BACKGROUND/AIMS: This study aimed to evaluate whether wedge resection or S4bS5 resection was the more beneficial hepatectomy procedure for patients with locally advanced gallbladder carcinoma. METHODOLOGY: A retrospective analysis of 70 patients who underwent either wedge resection (n=58) or S4bS5 resection (n=12) for locally advanced gallbladder carcinoma without clinically evident liver metastases was conducted. Clinicopathological characteristics, histological features of hepatic invasion and surgical outcomes were analyzed. RESULTS: Sixteen patients had tumors with hepatic invasion. Of the 16 patients with hepatic invasion, 6 had direct liver invasion alone and 10 had portal tract invasion featuring intrahepatic stromal invasion (n=5), intrahepatic lymphatic invasion (n=4) and intrahepatic venous invasion (n=l). The hepatectomy procedure was not significantly associated with survival after resection (p=0.518) as patients who underwent wedge resection showed an overall cumulative 3-year survival rate of 74% compared with 60% for patients who underwent S4bS5 resection. The Cox proportional hazard regression analysis revealed that pT classification (p<0.001), pM classification (p=0.001) and resection of the extrahepatic bile duct (p=0.048) were independently significant factors associated with survival after resection. CONCLUSIONS: Hepatectomy procedure may not significantly affect surgical outcomes in patients with gallbladder carcinoma. Partial hepatectomy involving the gallbladder bed is critical due to possible tumor cells. PubMed","prediction_labels":"HUMAN"},{"cleaned":"effect marital status survival patients gallbladder cancer treated surgical resection population based study marital status reported independent prognostic factor survival various cancers rarely studied gallbladder cancer treated surgical resection retrospectively studied surveillance epidemiology end results seer population based data identified 9 041 cases gallbladder cancer surgical treatment 1988 2013 patients categorized according marital status married never married widowed divorced separated patients widowed group higher proportion women within group comparisons higher rate white race greater proportion older 60 years patients frequency adenocarcinoma greater number tumors well moderate pathological grading prevalence localized seer stage statistically significant p 0 001 marital status confirmed independent prognostic factor multivariate analysis p 0 001 married patients higher 5 year gallbladder cancer cause specific survival unmarried patients p 0 001 conversely widowed patients lowest gallbladder cancer cause specific survival compared patients conclusions marital status important prognostic risk factor survival patients gallbladder cancer treated surgical resection widowed patients highest risk death compared groups stn","probabilities":0.9799733,"Title":"Effect Of Marital Status On The Survival Of Patients With Gallbladder Cancer Treated With Surgical Resection: A Population-Based Study","Abstract":"Marital status has been reported as an independent prognostic factor for survival in various cancers, but it has been rarely studied in gallbladder cancer treated by surgical resection. We retrospectively studied Surveillance, Epidemiology, and End Results (SEER) population-based data and identified 9,041 cases of gallbladder cancer with surgical treatment between 1988 and 2013. The patients were categorized according to marital status, as \"married,\" \"never married,\" \"widowed,\" or \"divorced/separated.\" Patients in the widowed group had a higher proportion of women within-group comparisons, a higher rate of white race, a greater proportion of older (≥ 60 years) patients, more frequency of adenocarcinoma, a greater number of tumors at well/moderate pathological grading, and more prevalence at the localized SEER stage, all of which were statistically significant (P < 0.001). Marital status was confirmed to be an independent prognostic factor by multivariate analysis (P < 0.001). Married patients had higher 5-year gallbladder cancer cause-specific survival than unmarried patients (P < 0.001); conversely, widowed patients had the lowest gallbladder cancer cause-specific survival compared with all other patients. Conclusions marital status is an important prognostic risk factor for survival in patients with gallbladder cancer treated with surgical resection. Widowed patients have the highest risk of death compared with other groups.","Source":"STN","category":"HUMAN","training_data":"Effect Of Marital Status On The Survival Of Patients With Gallbladder Cancer Treated With Surgical Resection: A Population-Based Study Marital status has been reported as an independent prognostic factor for survival in various cancers, but it has been rarely studied in gallbladder cancer treated by surgical resection. We retrospectively studied Surveillance, Epidemiology, and End Results (SEER) population-based data and identified 9,041 cases of gallbladder cancer with surgical treatment between 1988 and 2013. The patients were categorized according to marital status, as \"married,\" \"never married,\" \"widowed,\" or \"divorced/separated.\" Patients in the widowed group had a higher proportion of women within-group comparisons, a higher rate of white race, a greater proportion of older (≥ 60 years) patients, more frequency of adenocarcinoma, a greater number of tumors at well/moderate pathological grading, and more prevalence at the localized SEER stage, all of which were statistically significant (P < 0.001). Marital status was confirmed to be an independent prognostic factor by multivariate analysis (P < 0.001). Married patients had higher 5-year gallbladder cancer cause-specific survival than unmarried patients (P < 0.001); conversely, widowed patients had the lowest gallbladder cancer cause-specific survival compared with all other patients. Conclusions marital status is an important prognostic risk factor for survival in patients with gallbladder cancer treated with surgical resection. Widowed patients have the highest risk of death compared with other groups. STN","prediction_labels":"HUMAN"},{"cleaned":"incidentally detected gallbladder polyps malignant retrospective single institution study 108 patients purpose determine natural history gallbladder gb polyps less 10 mm incidentally detected ultrasonography us propose management guidelines lesions method database search polyp us examinations gb january 1 2008 december 31 2014 single institution performed subsequent us reports reviewed determine changes gb polyp size electronic medical record searched obtain clinical pathologic follow results gb polyps identified 108 patients male 81 females 19 median age 50 9 years majority polyps detected comprehensive health check ultrasound abdomen evaluation pain abdomen mean size polyps 4 7 2 15 mm range 1 mm 15 mm follow usg 3 months polyp size 43 patients showed complete resolution 32 12 size polyp reduced 10 increase size 956 cholecystectomies done 20 1 67 gb polyps 17 abdominal pain 3 family history gb cancer 20 operated 8 gb specimens 37 polyps histopathology remaining stones none showed evidence dysplasia neoplasia ultrasound abdomen low sensitivity 39 conclusions risk gb malignancy resulting incidentally detected polyps extremely low incidentally detected gb polyps measuring 10 mm less may require additional follow although studies required substantiate google scholar","probabilities":0.9799733,"Title":"Incidentally Detected Gallbladder Polyps: Is It Malignant? Retrospective Single Institution Study Of 108 Patients","Abstract":"Purpose: To determine the natural history of gallbladder (GB) polyps less than 10 mm incidentally detected at ultrasonography (US) and to propose management guidelines for these lesions.\nMethod: A database search for “polyp” in all US examinations of the GB between January 1, 2008, and December 31, 2014 at a single institution was performed. All subsequent US reports were reviewed to determine changes in GB polyp size. The electronic medical record was searched to obtain clinical and pathologic follow-up.\nResults: GB Polyps were identified in 108 patients (Male – 81%, Females – 19%) with Median age – 50.9 years. Majority of polyps were detected during comprehensive health check up or during ultrasound abdomen evaluation for pain abdomen.\nThe mean size of the polyps were 4.7 ± 2.15 mm (range of 1 mm to 15 mm). On follow up USG at 3 months, Polyp was of same size in 43% of the patients, it showed complete resolution in 32%, and in 12% the size of polyp had reduced. Only 10% had increase in size. Out of 956 cholecystectomies done, 20 (1.67%) were for GB Polyps (17-abdominal pain, 3-family history of GB cancer). Out of 20 that were operated, only 8 GB specimens (37%) had polyps on histopathology and remaining had stones.\nNone of them showed any evidence of dysplasia or neoplasia.Ultrasound abdomen had a low sensitivity (39%).\nConclusions: The risk of GB malignancy resulting from incidentally detected polyps is extremely low. Incidentally detected GB polyps measuring 10 mm less may require no additional follow-up, although further studies are required to substantiate.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidentally Detected Gallbladder Polyps: Is It Malignant? Retrospective Single Institution Study Of 108 Patients Purpose: To determine the natural history of gallbladder (GB) polyps less than 10 mm incidentally detected at ultrasonography (US) and to propose management guidelines for these lesions.\nMethod: A database search for “polyp” in all US examinations of the GB between January 1, 2008, and December 31, 2014 at a single institution was performed. All subsequent US reports were reviewed to determine changes in GB polyp size. The electronic medical record was searched to obtain clinical and pathologic follow-up.\nResults: GB Polyps were identified in 108 patients (Male – 81%, Females – 19%) with Median age – 50.9 years. Majority of polyps were detected during comprehensive health check up or during ultrasound abdomen evaluation for pain abdomen.\nThe mean size of the polyps were 4.7 ± 2.15 mm (range of 1 mm to 15 mm). On follow up USG at 3 months, Polyp was of same size in 43% of the patients, it showed complete resolution in 32%, and in 12% the size of polyp had reduced. Only 10% had increase in size. Out of 956 cholecystectomies done, 20 (1.67%) were for GB Polyps (17-abdominal pain, 3-family history of GB cancer). Out of 20 that were operated, only 8 GB specimens (37%) had polyps on histopathology and remaining had stones.\nNone of them showed any evidence of dysplasia or neoplasia.Ultrasound abdomen had a low sensitivity (39%).\nConclusions: The risk of GB malignancy resulting from incidentally detected polyps is extremely low. Incidentally detected GB polyps measuring 10 mm less may require no additional follow-up, although further studies are required to substantiate. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"defining long term survivors following resection intrahepatic cholangiocarcinoma background intrahepatic cholangiocarcinoma icc aggressive primary tumor liver surgery remains cornerstone therapy long term survival following curative intent resection generally poor aim current study define incidence actual long term survivors well identify clinicopathological factors associated long term survival methods patients underwent curative intent liver resection icc 1990 2015 identified using multi institutional database overall 679 patients alive 5 years follow died follow prognostic factors among patients long term survivors lt overall survival os 5 compared patients non long term survivors non lt os 5 results among 1154 patients underwent liver resection icc 5 10 year os 39 6 20 3 actual lt survival rate 13 3 excluding 475 patients survived 5 years well patients alive yet 5 years follow 153 patients 22 5 survived 5 years included lt group 526 patients 77 5 died 5 years date surgery included non lt group factors associated surviving 5 years included perineural invasion 4 78 95 ci 1 92 11 8 p 0 001 intrahepatic metastasis 3 75 95 ci 0 85 16 6 p 0 082 satellite lesions 2 12 95 ci 1 15 3 90 p 0 016 n1 status 4 64 95 ci 1 77 12 2 p 0 002 icc 5 cm 2 40 95 ci 1 54 3 74 p 0 001 direct invasion adjacent organ 3 98 95 ci 1 18 13 4 p 0 026 however subset patients 10 pathological characteristics lt conclusion icc generally associated poor prognosis patients lt fact even subset patients traditional adverse prognostic factors survived long term stn","probabilities":0.9799733,"Title":"Defining Long-Term Survivors Following Resection Of Intrahepatic Cholangiocarcinoma","Abstract":"Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival. \r\n\r\n Methods: Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS < 5). \r\n\r\n Results: Among the 1154 patients who underwent liver resection for ICC, 5- and 10-year OS were 39.6 and 20.3% while the actual LT survival rate was 13.3%. After excluding 475 patients who survived < 5 years, as well as patients were alive yet had < 5 years of follow-up, 153 patients (22.5%) who survived ≥ 5 years were included in the LT group, while 526 patients (77.5%) who died < 5 years from the date of surgery were included in the non-LT group. Factors associated with not surviving to 5 years included perineural invasion (OR 4.78, 95% CI, 1.92-11.8; p = 0.001), intrahepatic metastasis (OR 3.75, 95% CI, 0.85-16.6, p = 0.082), satellite lesions (OR 2.12, 95% CI, 1.15-3.90, p = 0.016), N1 status (OR 4.64, 95% CI, 1.77-12.2; p = 0.002), ICC > 5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (< 10%) who had these pathological characteristics were LT. \r\n\r\n Conclusion: While ICC is generally associated with a poor prognosis, some patients will be LT. In fact, even a subset of patients with traditional adverse prognostic factors survived long term.","Source":"STN","category":"HUMAN","training_data":"Defining Long-Term Survivors Following Resection Of Intrahepatic Cholangiocarcinoma Background: Intrahepatic cholangiocarcinoma (ICC) is an aggressive primary tumor of the liver. While surgery remains the cornerstone of therapy, long-term survival following curative-intent resection is generally poor. The aim of the current study was to define the incidence of actual long-term survivors, as well as identify clinicopathological factors associated with long-term survival. \r\n\r\n Methods: Patients who underwent a curative-intent liver resection for ICC between 1990 and 2015 were identified using a multi-institutional database. Overall, 679 patients were alive with ≥ 5 years of follow-up or had died during follow-up. Prognostic factors among patients who were long-term survivors (LT) (overall survival (OS) ≥ 5) were compared with patients who were not non-long-term survivors (non-LT) (OS < 5). \r\n\r\n Results: Among the 1154 patients who underwent liver resection for ICC, 5- and 10-year OS were 39.6 and 20.3% while the actual LT survival rate was 13.3%. After excluding 475 patients who survived < 5 years, as well as patients were alive yet had < 5 years of follow-up, 153 patients (22.5%) who survived ≥ 5 years were included in the LT group, while 526 patients (77.5%) who died < 5 years from the date of surgery were included in the non-LT group. Factors associated with not surviving to 5 years included perineural invasion (OR 4.78, 95% CI, 1.92-11.8; p = 0.001), intrahepatic metastasis (OR 3.75, 95% CI, 0.85-16.6, p = 0.082), satellite lesions (OR 2.12, 95% CI, 1.15-3.90, p = 0.016), N1 status (OR 4.64, 95% CI, 1.77-12.2; p = 0.002), ICC > 5 cm (OR 2.40, 95% CI, 1.54-3.74, p < 0.001), and direct invasion of an adjacent organ (OR 3.98, 95% CI, 1.18-13.4, p = 0.026). However, a subset of patients (< 10%) who had these pathological characteristics were LT. \r\n\r\n Conclusion: While ICC is generally associated with a poor prognosis, some patients will be LT. In fact, even a subset of patients with traditional adverse prognostic factors survived long term. STN","prediction_labels":"HUMAN"},{"cleaned":"expression phospho akt1 phospho mtor associated favorable prognosis independent pten expression intrahepatic cholangiocarcinomas akt1 signaling pathway important regulation protein synthesis cell survival implications carcinogenesis study explored prognostic significance akt1 pathway intrahepatic cholangiocarcinomas investigated status phosphatase tensin homolog deleted chromosome 10 pten phosphorylated p akt1 p akt1 p mammalian target rapamycin p mtor p p70 ribosomal protein s6 kinase p rps6kb2 p eukaryotic initiation factor 4e binding protein 1 p eif4ebp1 101 intrahepatic cholangiocarcinomas immunohistochemistry western blot analysis performed verify expression levels p akt1 p mtor relationship protein expression clinicopathological data correlations protein expression levels explored overexpression p akt1 p mtor pten associated better survival patients intrahepatic cholangiocarcinoma p 0 0137 0 0194 0 0337 respectively multivariate analysis pten independent prognostic factor p akt1 showed tendency p 0 032 0 051 respectively overexpression p mtor correlated well moderately differentiated tumors p 0 001 tumors without metastasis p 0 046 expression levels akt1 signaling pathway proteins study showed positive correlations except pten aberrant expressions p akt1 p mtor intrahepatic cholangiocarcinoma associated favorable prognosis possibly pten independent manner results indicate dysregulation akt1 pathway may important role development intrahepatic cholangiocarcinoma necessarily progression disease stn","probabilities":0.9467213,"Title":"The Expression Of Phospho-Akt1 And Phospho-Mtor Is Associated With A Favorable Prognosis Independent Of Pten Expression In Intrahepatic Cholangiocarcinomas","Abstract":"AKT1 signaling pathway is important for the regulation of protein synthesis and cell survival with implications in carcinogenesis. In this study, we explored the prognostic significance of AKT1 pathway in intrahepatic cholangiocarcinomas. We investigated the status of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphorylated (p) AKT1 (p-AKT1), p-mammalian target of rapamycin (p-MTOR), p-p70 ribosomal protein S6 kinase (p-RPS6KB2) and p-eukaryotic initiation factor 4E-binding protein-1 (p-EIF4EBP1) in 101 intrahepatic cholangiocarcinomas by immunohistochemistry. Western blot analysis was performed to verify the expression levels of p-AKT1 and p-MTOR. The relationship of protein expression with clinicopathological data and the correlations of protein expression levels were explored. The overexpression of p-AKT1, p-MTOR, and PTEN was associated with a better survival in patients with intrahepatic cholangiocarcinoma (P=0.0137, 0.0194, and 0.0337, respectively). In a multivariate analysis, PTEN was an independent prognostic factor, and p-AKT1 showed tendency (P=0.032 and 0.051, respectively). The overexpression of p-MTOR was correlated with well-to-moderately differentiated tumors (P<0.001) and tumors without metastasis (P=0.046). Expression levels of the AKT1 signaling pathway proteins in this study showed positive correlations with each other, except for PTEN. Aberrant expressions of p-AKT1 and p-MTOR in intrahepatic cholangiocarcinoma were associated with a favorable prognosis, possibly in a PTEN-independent manner. Our results indicate that dysregulation of the AKT1 pathway may have an important role in the development of intrahepatic cholangiocarcinoma, but not necessarily in the progression of the disease.","Source":"STN","category":"ANIMAL","training_data":"The Expression Of Phospho-Akt1 And Phospho-Mtor Is Associated With A Favorable Prognosis Independent Of Pten Expression In Intrahepatic Cholangiocarcinomas AKT1 signaling pathway is important for the regulation of protein synthesis and cell survival with implications in carcinogenesis. In this study, we explored the prognostic significance of AKT1 pathway in intrahepatic cholangiocarcinomas. We investigated the status of phosphatase and tensin homolog deleted on chromosome 10 (PTEN), phosphorylated (p) AKT1 (p-AKT1), p-mammalian target of rapamycin (p-MTOR), p-p70 ribosomal protein S6 kinase (p-RPS6KB2) and p-eukaryotic initiation factor 4E-binding protein-1 (p-EIF4EBP1) in 101 intrahepatic cholangiocarcinomas by immunohistochemistry. Western blot analysis was performed to verify the expression levels of p-AKT1 and p-MTOR. The relationship of protein expression with clinicopathological data and the correlations of protein expression levels were explored. The overexpression of p-AKT1, p-MTOR, and PTEN was associated with a better survival in patients with intrahepatic cholangiocarcinoma (P=0.0137, 0.0194, and 0.0337, respectively). In a multivariate analysis, PTEN was an independent prognostic factor, and p-AKT1 showed tendency (P=0.032 and 0.051, respectively). The overexpression of p-MTOR was correlated with well-to-moderately differentiated tumors (P<0.001) and tumors without metastasis (P=0.046). Expression levels of the AKT1 signaling pathway proteins in this study showed positive correlations with each other, except for PTEN. Aberrant expressions of p-AKT1 and p-MTOR in intrahepatic cholangiocarcinoma were associated with a favorable prognosis, possibly in a PTEN-independent manner. Our results indicate that dysregulation of the AKT1 pathway may have an important role in the development of intrahepatic cholangiocarcinoma, but not necessarily in the progression of the disease. STN","prediction_labels":"ANIMAL"},{"cleaned":"patterns prognostic significance lymph node dissection surgical treatment perihilar intrahepatic cholangiocarcinoma introduction prognostic significance lymph node dissection lnd number status harvested lymph nodes lns lymph node ratio lnr still debate intrahepatic icc perihilar pcc cholangiocarcinoma aims study evaluate prognostic value extent ln dissection number positive lns distribution positive lns along different ln stations lnr cohort patients icc pcc underwent surgical resection compare different prognostic values lymph node involvement material methods retrospective analysis done evaluating extent lnd number status location harvested lns cohort 145 patients cholangiocarcinoma submitted surgical resection curative intent 1990 2012 results seventy patients icc 75 pcc median survival times patients n0 n tumors 42 19 months icc patients p 0 05 42 22 months pcc patients p 0 01 patients without ln metastases median survival times patients three lns retrieved three lns retrieved 38 69 months icc patients p 0 05 18 43 months pcc patients p 0 04 respectively n patients location positive lns hepatoduodenal ligament regional stations influence overall survival icc pcc patients p 0 6 median survival times patients lnrs 0 0 25 43 19 months icc patients p 0 01 0 0 25 group reach value pcc patients median survival 0 0 0 25 0 25 groups patients 42 23 11 months p 0 01 respectively conclusions ln metastasis major prognostic factor surgical resection cholangiocarcinoma number harvested lns lnr showed high prognostic value icc pcc pubmed","probabilities":0.9799733,"Title":"Patterns and prognostic significance of lymph node dissection for surgical treatment of perihilar and intrahepatic cholangiocarcinoma","Abstract":"INTRODUCTION: The prognostic significance of lymph node dissection (LND), the number and status of harvested lymph nodes (LNs), and the lymph node ratio (LNR) are still under debate in intrahepatic (ICC) and perihilar (PCC) cholangiocarcinoma. The aims of this study were to evaluate the prognostic value of the extent of LN dissection, the number of positive LNs, the distribution of positive LNs along different LN stations, and the LNR in a cohort of patients with ICC and PCC who underwent surgical resection and to compare the different prognostic values of lymph node involvement. MATERIAL AND METHODS: A retrospective analysis was done evaluating extent of LND, number, status, and location of harvested LNs in a cohort of 145 patients with cholangiocarcinoma submitted to surgical resection with curative intent from 1990 to 2012. RESULTS: Seventy patients had ICC and 75 had PCC. The median survival times of patients with N0 and N+ tumors were 42 and 19 months in ICC patients (p = 0.05) and 42 and 22 months in PCC patients (p = 0.01). In patients without LN metastases, the median survival times of patients with up to three LNs retrieved and with more than three LNs retrieved were 38 and 69 months in ICC patients (p = 0.05) and 18 and 43 months in PCC patients (p = 0.04), respectively. In N+ patients, the location of positive LNs (hepatoduodenal ligament or other regional stations) did not influence overall survival in ICC or PCC patients (p = 0.6). The median survival times of patients with LNRs of 0 and >0.25 were 43 and 19 months in ICC patients (p = 0.01); the 0-0.25 group did not reach the value. In PCC patients, median survival of 0, 0-0.25, and >0.25 groups of patients were 42, 23, and 11 months (p = 0.01), respectively. CONCLUSIONS: LN metastasis is a major prognostic factor after surgical resection of cholangiocarcinoma. The number of harvested LNs and the LNR showed a high prognostic value in ICC and PCC.","Source":"PubMed","category":"HUMAN","training_data":"Patterns and prognostic significance of lymph node dissection for surgical treatment of perihilar and intrahepatic cholangiocarcinoma INTRODUCTION: The prognostic significance of lymph node dissection (LND), the number and status of harvested lymph nodes (LNs), and the lymph node ratio (LNR) are still under debate in intrahepatic (ICC) and perihilar (PCC) cholangiocarcinoma. The aims of this study were to evaluate the prognostic value of the extent of LN dissection, the number of positive LNs, the distribution of positive LNs along different LN stations, and the LNR in a cohort of patients with ICC and PCC who underwent surgical resection and to compare the different prognostic values of lymph node involvement. MATERIAL AND METHODS: A retrospective analysis was done evaluating extent of LND, number, status, and location of harvested LNs in a cohort of 145 patients with cholangiocarcinoma submitted to surgical resection with curative intent from 1990 to 2012. RESULTS: Seventy patients had ICC and 75 had PCC. The median survival times of patients with N0 and N+ tumors were 42 and 19 months in ICC patients (p = 0.05) and 42 and 22 months in PCC patients (p = 0.01). In patients without LN metastases, the median survival times of patients with up to three LNs retrieved and with more than three LNs retrieved were 38 and 69 months in ICC patients (p = 0.05) and 18 and 43 months in PCC patients (p = 0.04), respectively. In N+ patients, the location of positive LNs (hepatoduodenal ligament or other regional stations) did not influence overall survival in ICC or PCC patients (p = 0.6). The median survival times of patients with LNRs of 0 and >0.25 were 43 and 19 months in ICC patients (p = 0.01); the 0-0.25 group did not reach the value. In PCC patients, median survival of 0, 0-0.25, and >0.25 groups of patients were 42, 23, and 11 months (p = 0.01), respectively. CONCLUSIONS: LN metastasis is a major prognostic factor after surgical resection of cholangiocarcinoma. The number of harvested LNs and the LNR showed a high prognostic value in ICC and PCC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic role programmed death ligand 1 expression patients biliary tract cancer meta analysis previous studies investigated prognostic role programmed death ligand 1 pd l1 expression patients biliary tract cancer btc however results remained controversial therefore conducted current meta analysis aim clarifying association pd l1 expression prognosis well several important clinicopathological features btc searched pubmed embase web science relevant studies studies detected pd l1 expression tumor cells using immunohistochemistry ihc selected pooled hazard ratios hrs pooled odds ratios ors 95 confidence intervals cis calculated estimate correlations total 15 independent studies 1 776 patients included meta analysis pooled data demonstrated high pd l1 expression associated poor overall survival n 15 hr 1 79 95 ci 1 55 2 07 p 0 001 correlation pd l1 expression disease free survival significant n 6 hr 1 38 95 ci 1 00 1 91 p 0 051 addition significant correlation observed pd l1 expression clinical features patients btc study results showed pd l1 expression play pivotal role effective factor poor prognosis patients btc stn","probabilities":0.9799733,"Title":"Prognostic Role Of Programmed Death-Ligand 1 Expression In Patients With Biliary Tract Cancer: A Meta-Analysis","Abstract":"Previous studies investigated the prognostic role of programmed death-ligand 1 (PD-L1) expression in patients with biliary tract cancer (BTC); however, the results remained controversial. Therefore, we conducted the current meta-analysis with the aim of clarifying the association between PD-L1 expression and prognosis as well as with several important clinicopathological features of BTC. We searched PubMed, Embase, and Web of Science for relevant studies. Studies that detected PD-L1 expression in tumor cells by using immunohistochemistry (IHC) were selected. Pooled hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the correlations. In total, 15 independent studies with 1,776 patients were included in this meta-analysis. The pooled data demonstrated that high PD-L1 expression was associated with poor overall survival (n=15, HR=1.79, 95% CI=1.55-2.07, p<0.001). The correlation between PD-L1 expression and disease-free survival was not significant (n=6, HR=1.38, 95% CI=1.00-1.91, p=0.051). In addition, no significant correlation was observed between PD-L1 expression and clinical features in patients with BTC. Our study results showed that PD-L1 expression could play a pivotal role as an effective factor of poor prognosis in patients with BTC.","Source":"STN","category":"HUMAN","training_data":"Prognostic Role Of Programmed Death-Ligand 1 Expression In Patients With Biliary Tract Cancer: A Meta-Analysis Previous studies investigated the prognostic role of programmed death-ligand 1 (PD-L1) expression in patients with biliary tract cancer (BTC); however, the results remained controversial. Therefore, we conducted the current meta-analysis with the aim of clarifying the association between PD-L1 expression and prognosis as well as with several important clinicopathological features of BTC. We searched PubMed, Embase, and Web of Science for relevant studies. Studies that detected PD-L1 expression in tumor cells by using immunohistochemistry (IHC) were selected. Pooled hazard ratios (HRs) and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the correlations. In total, 15 independent studies with 1,776 patients were included in this meta-analysis. The pooled data demonstrated that high PD-L1 expression was associated with poor overall survival (n=15, HR=1.79, 95% CI=1.55-2.07, p<0.001). The correlation between PD-L1 expression and disease-free survival was not significant (n=6, HR=1.38, 95% CI=1.00-1.91, p=0.051). In addition, no significant correlation was observed between PD-L1 expression and clinical features in patients with BTC. Our study results showed that PD-L1 expression could play a pivotal role as an effective factor of poor prognosis in patients with BTC. STN","prediction_labels":"HUMAN"},{"cleaned":"improvement surgical treatment patients gallbladder cancer analysis 208 consecutive cases past decade objectives aim study determine improvement survival patients gallbladder cancer treated surgical procedures methods retrospective review patients gallbladder cancer admitted past 11 years conducted patients categorized two periods period 1 1 january 2000 31 december 2005 group 1 n 77 period 2 1 january 2006 31 december 2010 group 2 n 131 results two groups similar age sex distribution symptoms patients advanced stage group 2 p 0 001 patients group 2 treated aggressive surgical procedures compared group 1 patients group 2 better surgical outcomes longer 5 year overall survival 9 vs 19 p 0 040 disease free survival p 0 017 median survival group 1 14 7 months group 2 22 3 months patients underwent r0 resection group 2 better survival group 1 p 0 009 similar survival underwent non r0 resection periods p 0 108 conclusions significant improvement disease free survival long term survival results observed past decade pubmed","probabilities":0.9799733,"Title":"The improvement of surgical treatment for patients with gallbladder cancer: analysis of 208 consecutive cases over the past decade","Abstract":"OBJECTIVES: The aim of this study was to determine if there has been improvement in survival for patients with gallbladder cancer treated with surgical procedures. METHODS: A retrospective review of all patients with gallbladder cancer admitted during the past 11 years was conducted. The patients were categorized into two periods: period 1, from 1 January 2000 to 31 December 2005 (group 1, n = 77); and period 2, from 1 January 2006 to 31 December 2010 (group 2, n = 131). RESULTS: The two groups have similar age, sex distribution, and symptoms. There were more patients with advanced stage in group 2 (P = 0.001). And patients in group 2 were treated with more aggressive surgical procedures compared with group 1. Patients of group 2 had a better surgical outcomes and longer 5-year overall survival (9 % vs. 19 %, P = 0.040) and disease-free survival (P = 0.017). Median survival in group 1 was 14.7 months, while in group 2 it was 22.3 months. Patients underwent R0 resection in group 2 had better survival than that in group 1 (P = 0.009), while they had similar survival for those who underwent non-R0 resection in both periods (P = 0.108). CONCLUSIONS: A significant improvement of disease-free survival and long-term survival results was observed in the past decade.","Source":"PubMed","category":"HUMAN","training_data":"The improvement of surgical treatment for patients with gallbladder cancer: analysis of 208 consecutive cases over the past decade OBJECTIVES: The aim of this study was to determine if there has been improvement in survival for patients with gallbladder cancer treated with surgical procedures. METHODS: A retrospective review of all patients with gallbladder cancer admitted during the past 11 years was conducted. The patients were categorized into two periods: period 1, from 1 January 2000 to 31 December 2005 (group 1, n = 77); and period 2, from 1 January 2006 to 31 December 2010 (group 2, n = 131). RESULTS: The two groups have similar age, sex distribution, and symptoms. There were more patients with advanced stage in group 2 (P = 0.001). And patients in group 2 were treated with more aggressive surgical procedures compared with group 1. Patients of group 2 had a better surgical outcomes and longer 5-year overall survival (9 % vs. 19 %, P = 0.040) and disease-free survival (P = 0.017). Median survival in group 1 was 14.7 months, while in group 2 it was 22.3 months. Patients underwent R0 resection in group 2 had better survival than that in group 1 (P = 0.009), while they had similar survival for those who underwent non-R0 resection in both periods (P = 0.108). CONCLUSIONS: A significant improvement of disease-free survival and long-term survival results was observed in the past decade. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidental gallbladder cancer surgeon suspicious background preoperative predictors incidental gallbladder cancer igbc poorly defined despite frequency cholecystectomy performed objective study define incidence consider risk factors igbc cholecystectomy methods american college surgeons national surgical quality improvement program acs nsqip database 2005 2009 used identify patients underwent cholecystectomy n 91 260 patients international classification diseases ninth revision diagnosis gallbladder malignancy underwent laparoscopic cholecystectomy lc n 80 924 open cholecystectomy oc n 10 336 alone included results incidence igbc 0 19 n 170 cholecystectomy cases 0 05 lc 0 60 lc converted oc p 0 001 vs lc 1 13 oc p 0 001 vs others patients undergoing oc 17 3 times likely igbc lc patients age 65 years older asian african american race asa american society anesthesiologists class 3 diabetes mellitus hypertension weight loss 10 alkaline phosphatase levels 120 units l albumin levels 3 6 g dl less associated igbc multiple logistic regression identified oc age 65 years older asian african american race elevated alkaline phosphatase level female sex independent risk factors patients 1 2 3 4 factors 6 3 16 7 30 0 47 4 fold risk igbc respectively zero risk factor baseline 0 03 conclusions surgeons suspicion gbc heightened performing converting lc oc patients older asian african american female elevated alkaline phosphatase level stn","probabilities":0.9799733,"Title":"Incidental Gallbladder Cancer: When Should The Surgeon Be Suspicious?","Abstract":"Background: Preoperative predictors of incidental gallbladder cancer (iGBC) have been poorly defined despite the frequency with which cholecystectomy is performed. The objective of this study was to define the incidence of and consider risk factors for iGBC at cholecystectomy. \r\n\r\n Methods: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2009) was used to identify all patients who underwent cholecystectomy (N = 91,260). Patients with an International Classification of Diseases, Ninth Revision, diagnosis of gallbladder malignancy who underwent a laparoscopic cholecystectomy (LC; n = 80,924) or open cholecystectomy (OC; n = 10,336) alone were included. \r\n\r\n Results: The incidence of iGBC was 0.19% (n = 170) for all cholecystectomy cases, but 0.05% at LC, 0.60% at LC converted to OC (P < 0.001 vs LC), and 1.13% at OC (P < 0.001 vs others). Patients undergoing OC were 17.3 times more likely to have iGBC than LC patients. Age 65 years or older, Asian or African American race, ASA (American Society of Anesthesiologists) class 3 or more, diabetes mellitus, hypertension, weight loss more than 10%, alkaline phosphatase levels 120 units/L or more, and albumin levels 3.6 g/dL or less were associated with iGBC. Multiple logistic regression identified having an OC, age 65 years or older, Asian or African American race, an elevated alkaline phosphatase level, and female sex as independent risk factors. Patients with 1, 2, 3, and 4 of these factors had a 6.3-, 16.7-, 30.0-, and 47.4-fold risk of iGBC, respectively, from a zero-risk factor baseline of 0.03%. \r\n\r\n Conclusions: Surgeons' suspicion for GBC should be heightened when they are performing or converting from LC to OC and when patients are older, Asian or African American, female, and have an elevated alkaline phosphatase level.","Source":"STN","category":"HUMAN","training_data":"Incidental Gallbladder Cancer: When Should The Surgeon Be Suspicious? Background: Preoperative predictors of incidental gallbladder cancer (iGBC) have been poorly defined despite the frequency with which cholecystectomy is performed. The objective of this study was to define the incidence of and consider risk factors for iGBC at cholecystectomy. \r\n\r\n Methods: The American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database (2005-2009) was used to identify all patients who underwent cholecystectomy (N = 91,260). Patients with an International Classification of Diseases, Ninth Revision, diagnosis of gallbladder malignancy who underwent a laparoscopic cholecystectomy (LC; n = 80,924) or open cholecystectomy (OC; n = 10,336) alone were included. \r\n\r\n Results: The incidence of iGBC was 0.19% (n = 170) for all cholecystectomy cases, but 0.05% at LC, 0.60% at LC converted to OC (P < 0.001 vs LC), and 1.13% at OC (P < 0.001 vs others). Patients undergoing OC were 17.3 times more likely to have iGBC than LC patients. Age 65 years or older, Asian or African American race, ASA (American Society of Anesthesiologists) class 3 or more, diabetes mellitus, hypertension, weight loss more than 10%, alkaline phosphatase levels 120 units/L or more, and albumin levels 3.6 g/dL or less were associated with iGBC. Multiple logistic regression identified having an OC, age 65 years or older, Asian or African American race, an elevated alkaline phosphatase level, and female sex as independent risk factors. Patients with 1, 2, 3, and 4 of these factors had a 6.3-, 16.7-, 30.0-, and 47.4-fold risk of iGBC, respectively, from a zero-risk factor baseline of 0.03%. \r\n\r\n Conclusions: Surgeons' suspicion for GBC should be heightened when they are performing or converting from LC to OC and when patients are older, Asian or African American, female, and have an elevated alkaline phosphatase level. STN","prediction_labels":"HUMAN"},{"cleaned":"surgical treatment hilar cholangiocarcinoma university tokyo experience properly copy pasted go link click sst3 2 google scholar","probabilities":0.9799733,"Title":"Surgical Treatment For Hilar Cholangiocarcinoma; The University Of Tokyo Experience","Abstract":"Cannot be properly copy-pasted. Go through the link Click SST3-2","Source":"Google Scholar","category":"HUMAN","training_data":"Surgical Treatment For Hilar Cholangiocarcinoma; The University Of Tokyo Experience Cannot be properly copy-pasted. Go through the link Click SST3-2 Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prostate stem cell antigen presumable organ dependent tumor suppressor gene regulated gallbladder carcinogenesis gallbladder cancer gbc relatively rare high mortality rate one candidate molecule might involved gbc development prostate stem cell antigen psca glycosylphosphatidylinositol anchored cell surface antigen tissue specific pattern expression epithelium several organs prostate stomach bladder gallbladder regulated number cancers including prostate urinary bladder pancreatic cancers regulated esophageal gastric cancers suggesting psca oncogenic activity former tumor suppressor activity latter however precise function psca regulatory mechanism expression normal cancer cells yet determined study immunohistochemical analyses specific antibody revealed psca regulated non neoplastic gallbladder lesions cholesterolosis cholecystolithiasis cholecystitis 9 17 53 also adenocarcinoma 40 44 91 common neoplasm gallbladder analyses dna methylation status gbc cell lines bisulfite pyrosequencing reporter assay psca promoter activity suggested regulation explained least partly dna methylation moreover colony formation assay revealed psca cell proliferation inhibition activity gbc cell lines also observed vivo lines vivo vitro evidence suggest psca acting tumor suppressor gbc development stn","probabilities":0.9467213,"Title":"Prostate Stem Cell Antigen A Presumable Organ-Dependent Tumor Suppressor Gene Is Down-Regulated In Gallbladder Carcinogenesis","Abstract":"Gallbladder cancer (GBC) is relatively rare but has a high mortality rate. One candidate molecule which might be involved in GBC development is prostate stem cell antigen (PSCA), a glycosylphosphatidylinositol-anchored cell surface antigen with a tissue-specific pattern of expression in the epithelium of several organs, such as the prostate, stomach, bladder, and gallbladder. It is up-regulated in a number of cancers including prostate, urinary bladder, and pancreatic cancers, while it is down-regulated in esophageal and gastric cancers, suggesting that PSCA has an oncogenic activity in the former but a tumor suppressor activity in the latter. However, the precise function of PSCA and the regulatory mechanism for its expression in normal and cancer cells are yet to be determined. In this study, immunohistochemical analyses with a specific antibody revealed that PSCA is down-regulated in non-neoplastic gallbladder lesions such as cholesterolosis, cholecystolithiasis, and cholecystitis (9/17; 53%), and also in adenocarcinoma (40/44; 91%), a common neoplasm in gallbladder. Analyses of the DNA methylation status in the GBC cell lines by bisulfite-Pyrosequencing and a reporter assay for the PSCA promoter activity suggested that the down-regulation is explained, at least partly, by DNA methylation. Moreover, colony formation assay revealed that PSCA has cell-proliferation inhibition activity in the GBC cell lines, which was also observed in vivo. These lines of in vivo and in vitro evidence suggest that PSCA is acting as a tumor suppressor in GBC development.","Source":"STN","category":"ANIMAL","training_data":"Prostate Stem Cell Antigen A Presumable Organ-Dependent Tumor Suppressor Gene Is Down-Regulated In Gallbladder Carcinogenesis Gallbladder cancer (GBC) is relatively rare but has a high mortality rate. One candidate molecule which might be involved in GBC development is prostate stem cell antigen (PSCA), a glycosylphosphatidylinositol-anchored cell surface antigen with a tissue-specific pattern of expression in the epithelium of several organs, such as the prostate, stomach, bladder, and gallbladder. It is up-regulated in a number of cancers including prostate, urinary bladder, and pancreatic cancers, while it is down-regulated in esophageal and gastric cancers, suggesting that PSCA has an oncogenic activity in the former but a tumor suppressor activity in the latter. However, the precise function of PSCA and the regulatory mechanism for its expression in normal and cancer cells are yet to be determined. In this study, immunohistochemical analyses with a specific antibody revealed that PSCA is down-regulated in non-neoplastic gallbladder lesions such as cholesterolosis, cholecystolithiasis, and cholecystitis (9/17; 53%), and also in adenocarcinoma (40/44; 91%), a common neoplasm in gallbladder. Analyses of the DNA methylation status in the GBC cell lines by bisulfite-Pyrosequencing and a reporter assay for the PSCA promoter activity suggested that the down-regulation is explained, at least partly, by DNA methylation. Moreover, colony formation assay revealed that PSCA has cell-proliferation inhibition activity in the GBC cell lines, which was also observed in vivo. These lines of in vivo and in vitro evidence suggest that PSCA is acting as a tumor suppressor in GBC development. STN","prediction_labels":"ANIMAL"},{"cleaned":"clinicopathological features prognosis intrahepatic cholangiocarcinoma liver transplantation resection background intrahepatic cholangiocarcinoma icc incidentally diagnosed liver transplantation lt investigated clinicopathological features lt recipients icc compared prognosis control group material methods identified 16 recipients icc institutional database propensity score matched control group comprised 100 icc patients underwent hepatic resection hr results icc incidence 0 5 adult lt patients 1 2 adult recipients primary liver cancer mean age 58 0 4 8 years 15 male iccs diagnosed incidentally explanted livers mean icc tumor diameter 2 5 1 1 cm 14 recipients single tumor tumor stages 9 ii 5 iv 2 concurrent second primary liver cancer detected hepatocellular carcinoma 7 combined hepatocellular carcinoma cholangiocarcinoma 1 tumor recurrence patient survival rates 56 2 81 3 1 year 78 1 52 4 5 years respectively presence second cancer affect tumor recurrence p 0 959 patient survival p 0 737 3 patients early icc show icc recurrence compared control group tumor recurrence rate higher lt p 0 024 difference disappeared analysis confined recipients icc alone p 0 121 post recurrence survival different hr lt p 0 082 conclusions icc rarely diagnosed lt half patients second liver cancer post transplant prognosis icc poor except early icc thus strict surveillance mandatory pubmed","probabilities":0.9799733,"Title":"Clinicopathological Features and Prognosis of Intrahepatic Cholangiocarcinoma After Liver Transplantation and Resection","Abstract":"BACKGROUND Intrahepatic cholangiocarcinoma (ICC) can be incidentally diagnosed after liver transplantation (LT). We investigated the clinicopathological features of LT recipients with ICC and compared prognosis with that of the control group. MATERIAL AND METHODS We identified 16 recipients with ICC in our institutional database. The propensity score-matched control group comprised 100 ICC patients who underwent hepatic resection (HR). RESULTS ICC incidence was 0.5% in all adult LT patients and 1.2% in adult recipients with primary liver cancer. Mean age was 58.0±4.8 years and 15 were male. All ICCs were diagnosed incidentally in the explanted livers. Mean ICC tumor diameter was 2.5±1.1 cm and 14 recipients had a single tumor. Tumor stages were I in 9, II in 5, and IV in 2. Concurrent second primary liver cancer was detected as hepatocellular carcinoma in 7 and combined hepatocellular carcinoma-cholangiocarcinoma in 1. Tumor recurrence and patient survival rates were 56.2% and 81.3% at 1 year and 78.1% and 52.4% at 5 years, respectively. Presence of second cancer did not affect tumor recurrence (p=0.959) or patient survival (p=0.737). All 3 patients with very early ICC did not show ICC recurrence. Compared with the control group, the tumor recurrence rate was higher after LT (p=0.024), but this difference disappeared after analysis was confined to recipients with ICC alone (p=0.121). Post-recurrence survival was not different after HR and LT (p=0.082). CONCLUSIONS ICC is rarely diagnosed after LT and half of such patients have second liver cancer. Post-transplant prognosis of ICC is poor except for very early ICC; thus, strict surveillance is mandatory.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological Features and Prognosis of Intrahepatic Cholangiocarcinoma After Liver Transplantation and Resection BACKGROUND Intrahepatic cholangiocarcinoma (ICC) can be incidentally diagnosed after liver transplantation (LT). We investigated the clinicopathological features of LT recipients with ICC and compared prognosis with that of the control group. MATERIAL AND METHODS We identified 16 recipients with ICC in our institutional database. The propensity score-matched control group comprised 100 ICC patients who underwent hepatic resection (HR). RESULTS ICC incidence was 0.5% in all adult LT patients and 1.2% in adult recipients with primary liver cancer. Mean age was 58.0±4.8 years and 15 were male. All ICCs were diagnosed incidentally in the explanted livers. Mean ICC tumor diameter was 2.5±1.1 cm and 14 recipients had a single tumor. Tumor stages were I in 9, II in 5, and IV in 2. Concurrent second primary liver cancer was detected as hepatocellular carcinoma in 7 and combined hepatocellular carcinoma-cholangiocarcinoma in 1. Tumor recurrence and patient survival rates were 56.2% and 81.3% at 1 year and 78.1% and 52.4% at 5 years, respectively. Presence of second cancer did not affect tumor recurrence (p=0.959) or patient survival (p=0.737). All 3 patients with very early ICC did not show ICC recurrence. Compared with the control group, the tumor recurrence rate was higher after LT (p=0.024), but this difference disappeared after analysis was confined to recipients with ICC alone (p=0.121). Post-recurrence survival was not different after HR and LT (p=0.082). CONCLUSIONS ICC is rarely diagnosed after LT and half of such patients have second liver cancer. Post-transplant prognosis of ICC is poor except for very early ICC; thus, strict surveillance is mandatory. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment cholangiocarcinoma retrospective analysis single center experience background cholangiocarcinomas cc relatively rare neoplasms show rising incidence worldwide cc orginate epithelial cells lining intra extrahepatic biliary tract including gallbladder methods retrospectively evaluated 105 patients cc treated centre 2000 2010 collective consisted 45 women 42 9 60 men 57 1 median age 64 years 33 87 years 23 patients adipose 22 diabetic 23 suffered neoplasms different cc symptoms patients initial diagnosis cc 47 weight loss 39 upper abdominal pain 36 jaundice imaging diagnostics consisted ultrasonography endosonography computertomography ercp tumormarkers ca19 9 cea elevated 76 48 patients cc respectively localization cc 46 hilus klatskintumor 23 distal choledochal truct 20 intrahepatic 11 gallbladder results 57 patients 54 3 primary curative surgery cc considered 13 57 showed laparoscopy inoperability 3 48 patients treated palliative chemotherapy showed regression cc allowing surgery thus 47 105 45 underwent curative surgery cc surgical results 39 47 83 r0 resection 7 47 15 r1 resection 1 47 rx resection median recidive free survival patients r0 resection 14 4 months r1 resection 1 8 months mean survival time cc patients undergone curative surgery 22 months patients palliative chemotherapy 5 months 1 3 5 year survival curatively resected cc patients 78 39 21 respectively palliative chemotherapeutic treatment caused 26 2 5 0 respectively whole collective median survival chemotherapy mainly gemcitabine 9 months best supportive care 2 5 months conclusions resection cc treatment choice localized neoplasms advanced cc chemotherapy mainly based gemcitabine superior best supportive care google scholar","probabilities":0.9799733,"Title":"Treatment Of Cholangiocarcinoma: Retrospective Analysis Of A Single-Center Experience","Abstract":"Background: Cholangiocarcinomas (CC) are relatively rare neoplasms, but they show a rising incidence worldwide. CC orginate from epithelial cells lining the intra- and extrahepatic biliary tract including the gallbladder. \nMethods: We retrospectively evaluated 105 patients with CC treated in our centre between 2000 and 2010. This collective consisted of 45 women (42,9 %) and 60 men (57,1 %). The median age was 64 years (33 – 87 years). 23 % of the patients were adipose, 22 % were diabetic and 23 % suffered from neoplasms different from CC. Symptoms of patients at initial diagnosis of CC were: 47 % weight loss, 39 % upper abdominal pain, 36 % jaundice. Imaging diagnostics consisted of ultrasonography, endosonography, computertomography and eRCP. Tumormarkers as CA19-9 and CEA were elevated in 76 % and 48 % of patients with CC, respectively. Localization of CC: 46 % hilus (Klatskintumor), 23 % distal choledochal truct, 20 % intrahepatic, 11 % gallbladder. \nResults: For 57 patients (54,3 %) primary curative surgery of the CC was considered. 13/57 showed at laparoscopy inoperability. 3/48 patients treated with palliative chemotherapy showed regression of CC, allowing surgery. Thus, 47/105 (45 %) underwent curative surgery of CC. Surgical results: 39/47 (83 %) R0-resection, 7/47 (15 %) R1-resection, 1/47 Rx-resection. Median recidive – free survival for patients with R0-resection was 14,4 months, for R1-resection 1,8 months. The mean survival time of CC patients undergone curative surgery was 22 months, that of patients with palliative chemotherapy 5 months. 1 – 3 and 5 year survival for curatively resected CC patients were 78 %, 39 % and 21 %, respectively. Palliative chemotherapeutic treatment caused 26 %, 2,5 % and 0 %, respectively. In the whole collective, median survival under chemotherapy (mainly gemcitabine) was 9 months, with best supportive care 2,5 months. \nConclusions: Resection of CC is treatment of choice in localized neoplasms. In advanced CC chemotherapy mainly based on gemcitabine was superior to best supportive care.","Source":"Google Scholar","category":"HUMAN","training_data":"Treatment Of Cholangiocarcinoma: Retrospective Analysis Of A Single-Center Experience Background: Cholangiocarcinomas (CC) are relatively rare neoplasms, but they show a rising incidence worldwide. CC orginate from epithelial cells lining the intra- and extrahepatic biliary tract including the gallbladder. \nMethods: We retrospectively evaluated 105 patients with CC treated in our centre between 2000 and 2010. This collective consisted of 45 women (42,9 %) and 60 men (57,1 %). The median age was 64 years (33 – 87 years). 23 % of the patients were adipose, 22 % were diabetic and 23 % suffered from neoplasms different from CC. Symptoms of patients at initial diagnosis of CC were: 47 % weight loss, 39 % upper abdominal pain, 36 % jaundice. Imaging diagnostics consisted of ultrasonography, endosonography, computertomography and eRCP. Tumormarkers as CA19-9 and CEA were elevated in 76 % and 48 % of patients with CC, respectively. Localization of CC: 46 % hilus (Klatskintumor), 23 % distal choledochal truct, 20 % intrahepatic, 11 % gallbladder. \nResults: For 57 patients (54,3 %) primary curative surgery of the CC was considered. 13/57 showed at laparoscopy inoperability. 3/48 patients treated with palliative chemotherapy showed regression of CC, allowing surgery. Thus, 47/105 (45 %) underwent curative surgery of CC. Surgical results: 39/47 (83 %) R0-resection, 7/47 (15 %) R1-resection, 1/47 Rx-resection. Median recidive – free survival for patients with R0-resection was 14,4 months, for R1-resection 1,8 months. The mean survival time of CC patients undergone curative surgery was 22 months, that of patients with palliative chemotherapy 5 months. 1 – 3 and 5 year survival for curatively resected CC patients were 78 %, 39 % and 21 %, respectively. Palliative chemotherapeutic treatment caused 26 %, 2,5 % and 0 %, respectively. In the whole collective, median survival under chemotherapy (mainly gemcitabine) was 9 months, with best supportive care 2,5 months. \nConclusions: Resection of CC is treatment of choice in localized neoplasms. In advanced CC chemotherapy mainly based on gemcitabine was superior to best supportive care. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"comparison number versus ratio positive lymph nodes assessment lymph node status extrahepatic cholangiocarcinoma background study aimed compare utility number positive lymph nodes lymph node ratio lnr predicting survival resection extrahepatic cholangiocarcinoma methods retrospective analysis 142 consecutive patients underwent radical resection extrahepatic cholangiocarcinoma performed total 3066 regional lymph nodes resected median number nodes per patient 21 optimal cutoff values number positive nodes lnr determined using chi square scores calculated cox proportional hazards regression model results nodal disease found 59 patients 42 subsequent analysis impact nodal status survival 18 patients r1 2 resection 6 patients paraaortic nodal disease survive 5 years resection excluded optimal cutoff value number positive nodes 1 optimal cutoff value lnr 5 univariate analysis identified number positive nodes 0 1 2 p 0 005 lnr 0 0 5 5 p 0 007 significant prognostic factors multivariate analysis identified number positive nodes lnr independent prognostic factor p 0 012 5 year survival rates 64 patients positive nodes 46 patients one positive node 28 patients two positive nodes conclusions number positive lymph nodes predicts survival better lnr resection extrahepatic cholangiocarcinoma provided nodal evaluation sufficient pubmed","probabilities":0.9799733,"Title":"Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma. METHODS: A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model. RESULTS: Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or ≥2; P = 0.005) and the LNR (0, 0-5, or >5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes. CONCLUSIONS: The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient.","Source":"PubMed","category":"HUMAN","training_data":"Comparison of Number Versus Ratio of Positive Lymph Nodes in the Assessment of Lymph Node Status in Extrahepatic Cholangiocarcinoma BACKGROUND: This study aimed to compare the utility of the number of positive lymph nodes with the lymph node ratio (LNR) in predicting survival after resection of extrahepatic cholangiocarcinoma. METHODS: A retrospective analysis of 142 consecutive patients who underwent radical resection of extrahepatic cholangiocarcinoma was performed. A total of 3066 regional lymph nodes were resected. The median number of nodes per patient was 21. The optimal cutoff values for the number of positive nodes and the LNR were determined using the Chi square scores calculated by the Cox proportional hazards regression model. RESULTS: Nodal disease was found in 59 patients (42 %). In the subsequent analysis of the impact that nodal status has on survival, 18 patients with R1/2 resection and 6 patients with paraaortic nodal disease who did not survive for more than 5 years after resection were excluded. The optimal cutoff value for the number of positive nodes was 1, and the optimal cutoff value for the LNR was 5 %. Univariate analysis identified both the number of positive nodes (0, 1, or ≥2; P = 0.005) and the LNR (0, 0-5, or >5 %; P = 0.007) as significant prognostic factors. Multivariate analysis identified the number of positive nodes but not the LNR as an independent prognostic factor (P = 0.012). The 5-year survival rates were 64 % for the patients with no positive nodes, 46 % for the patients with one positive node, and 28 % for the patients with two or more positive nodes. CONCLUSIONS: The number of positive lymph nodes predicts survival better than the LNR after resection of extrahepatic cholangiocarcinoma, provided that nodal evaluation is sufficient. PubMed","prediction_labels":"HUMAN"},{"cleaned":"evaluation portal vein invasion distal cholangiocarcinoma borderline resectability background concept borderline resectability yet introduced extrahepatic cholangiocarcinoma ecc study surgical results ecc patients analyzed clarify implications surgery distal ecc portal vein pv invasion preliminary step introduction concept borderline resectability methods clinicopathological data 129 patients undergone pancreatoduodenectomy distal ecc reviewed retrospectively combined pv resection performed 10 patients clinicopathological variables evaluated using univariate multivariate analyses results pathological pv invasion observed eight 129 patients survival rates patients pv invasion significantly poorer patients without pv invasion 3 5 years surgery 17 0 versus 50 39 p 0 001 respectively presence pancreatic pv invasion tumor progression nodal status residual tumor significant prognostic factors univariate analysis multivariate analysis pv invasion significant independent predictive factor poor prognosis conclusions pv invasion distal ecc regarded indicating borderline resectability pubmed","probabilities":0.9799733,"Title":"Evaluation of portal vein invasion of distal cholangiocarcinoma as borderline resectability","Abstract":"BACKGROUND: The concept of borderline resectability has not yet been introduced for extrahepatic cholangiocarcinoma (ECC). In this study, the surgical results of ECC patients were analyzed to clarify the implications of surgery for distal ECC with portal vein (PV) invasion as a preliminary step for the introduction of the concept of borderline resectability. METHODS: The clinicopathological data of 129 patients who had undergone pancreatoduodenectomy of distal ECC were reviewed retrospectively. Combined PV resection was performed in 10 patients. The clinicopathological variables were evaluated using univariate and multivariate analyses. RESULTS: Pathological PV invasion was observed in eight of the 129 patients. The survival rates of patients with PV invasion were significantly poorer than those of patients without PV invasion: 3 and 5 years after surgery, 17% and 0% versus 50% and 39% (P < 0.001), respectively. Presence of pancreatic or PV invasion, tumor progression, nodal status, and residual tumor were significant prognostic factors on univariate analysis. On multivariate analysis, PV invasion was the only significant independent predictive factor of a poor prognosis. CONCLUSIONS: PV invasion of distal ECC should be regarded as indicating borderline resectability.","Source":"PubMed","category":"HUMAN","training_data":"Evaluation of portal vein invasion of distal cholangiocarcinoma as borderline resectability BACKGROUND: The concept of borderline resectability has not yet been introduced for extrahepatic cholangiocarcinoma (ECC). In this study, the surgical results of ECC patients were analyzed to clarify the implications of surgery for distal ECC with portal vein (PV) invasion as a preliminary step for the introduction of the concept of borderline resectability. METHODS: The clinicopathological data of 129 patients who had undergone pancreatoduodenectomy of distal ECC were reviewed retrospectively. Combined PV resection was performed in 10 patients. The clinicopathological variables were evaluated using univariate and multivariate analyses. RESULTS: Pathological PV invasion was observed in eight of the 129 patients. The survival rates of patients with PV invasion were significantly poorer than those of patients without PV invasion: 3 and 5 years after surgery, 17% and 0% versus 50% and 39% (P < 0.001), respectively. Presence of pancreatic or PV invasion, tumor progression, nodal status, and residual tumor were significant prognostic factors on univariate analysis. On multivariate analysis, PV invasion was the only significant independent predictive factor of a poor prognosis. CONCLUSIONS: PV invasion of distal ECC should be regarded as indicating borderline resectability. PubMed","prediction_labels":"HUMAN"},{"cleaned":"infection cancer global distribution burden diseases background infection one main risk factors cancer objectives epidemiology pathogenesis disease burden infection related cancers reviewed infectious agents findings chronic infection epstein barr virus hepatitis b c viruses kaposi sarcoma herpes virus human immunodeficiency virus hiv type 1 human papillomavirus hpv human cell lymphotropic virus type 1 helicobacter pylori clonorchis sinensis opisthorchis viverrini schistosoma haematobium associated nasopharyngeal carcinoma lymphoma leukemia including non hodgkin lymphoma hodgkin lymphoma burkitt lymphoma hepatocellular carcinoma kaposi sarcoma oropharyngeal carcinoma cervical carcinoma carcinoma anogential sites adult cell leukemia lymphoma gastric carcinoma cholangiocarcinoma urinary bladder cancer 2008 approximately 2 million new cancer cases 16 worldwide attributable infection infections prevented treated estimated 23 fewer cancers less developed regions world 7 fewer cancers developed regions conclusion widespread application existing public health methods prevention infection vaccination safer injection practices quality assured screening donated blood blood components antimicrobial treatments safer sex practices including minimizing one lifetime number sexual partners condom use substantial effect future burden cancer worldwide pubmed","probabilities":0.962963,"Title":"Infection and cancer: global distribution and burden of diseases","Abstract":"BACKGROUND: Infection is one of the main risk factors for cancer. OBJECTIVES: Epidemiology, pathogenesis, and disease burden of infection-related cancers were reviewed by infectious agents. FINDINGS: Chronic infection with Epstein-Barr virus, hepatitis B and C viruses, Kaposi sarcoma herpes virus, human immunodeficiency virus (HIV) type 1, human papillomavirus (HPV), human T-cell lymphotropic virus type 1, Helicobacter pylori, Clonorchis sinensis, Opisthorchis viverrini, and Schistosoma haematobium are associated with nasopharyngeal carcinoma; lymphoma and leukemia, including non-Hodgkin lymphoma, Hodgkin lymphoma, and Burkitt lymphoma; hepatocellular carcinoma; Kaposi sarcoma; oropharyngeal carcinoma; cervical carcinoma and carcinoma of other anogential sites; adult T-cell leukemia/lymphoma; gastric carcinoma; cholangiocarcinoma; and urinary bladder cancer. In 2008, approximately 2 million new cancer cases (16%) worldwide were attributable to infection. If these infections could be prevented and/or treated, it is estimated that there would be about 23% fewer cancers in less developed regions of the world, and about 7% fewer cancers in more developed regions. CONCLUSION: Widespread application of existing public health methods for the prevention of infection, such as vaccination, safer injection practices, quality-assured screening of all donated blood and blood components, antimicrobial treatments, and safer sex practices, including minimizing one's lifetime number of sexual partners and condom use, could have a substantial effect on the future burden of cancer worldwide.","Source":"PubMed","category":"HUMAN","training_data":"Infection and cancer: global distribution and burden of diseases BACKGROUND: Infection is one of the main risk factors for cancer. OBJECTIVES: Epidemiology, pathogenesis, and disease burden of infection-related cancers were reviewed by infectious agents. FINDINGS: Chronic infection with Epstein-Barr virus, hepatitis B and C viruses, Kaposi sarcoma herpes virus, human immunodeficiency virus (HIV) type 1, human papillomavirus (HPV), human T-cell lymphotropic virus type 1, Helicobacter pylori, Clonorchis sinensis, Opisthorchis viverrini, and Schistosoma haematobium are associated with nasopharyngeal carcinoma; lymphoma and leukemia, including non-Hodgkin lymphoma, Hodgkin lymphoma, and Burkitt lymphoma; hepatocellular carcinoma; Kaposi sarcoma; oropharyngeal carcinoma; cervical carcinoma and carcinoma of other anogential sites; adult T-cell leukemia/lymphoma; gastric carcinoma; cholangiocarcinoma; and urinary bladder cancer. In 2008, approximately 2 million new cancer cases (16%) worldwide were attributable to infection. If these infections could be prevented and/or treated, it is estimated that there would be about 23% fewer cancers in less developed regions of the world, and about 7% fewer cancers in more developed regions. CONCLUSION: Widespread application of existing public health methods for the prevention of infection, such as vaccination, safer injection practices, quality-assured screening of all donated blood and blood components, antimicrobial treatments, and safer sex practices, including minimizing one's lifetime number of sexual partners and condom use, could have a substantial effect on the future burden of cancer worldwide. PubMed","prediction_labels":"HUMAN"},{"cleaned":"osteopontin positive infiltrating tumor associated macrophages bulky ampullary cancer predict survival purpose tumor associated macrophages tams promote cancer cell proliferation distant metastases osteopontin opn overexpressed several human cancer cells tams therefore set determine role opn expressing macrophages cancer results 100 ampullary cancers diffuse cytoplasmic positivity opn found infiltrating tams 36 patients marginal tams 32 patients opn macrophages absent 32 patients expression patterns opn tams associated pancreatic invasion tumor stage tnm stage lymphovascular invasion recurrence peritoneal carcinomatosis patients stratified according median tumor size 2 cm patients tumor sizes 2 cm opn infiltrating tams poorer disease specific survival rate opn marginal tams macrophage associated cytokine expression ampullary cancer cells also assessed levels macrophage migration inhibitory factor mif cancer cells higher normal duodenal mucosa experimental design specimens ampullary cancer patients national cheng kung university hospital collected immunohistochemistry plasma opn measured enzyme linked immunosorbent assay tumor normal epithelial cells fresh tissues separated laser assisted microdissection reverse transcription polymerase chain reaction quantitative real time pcr analyses conclusions expression opn location tams bulky ampullary cancer predict recurrence addition cytoplasmic staining mif enhanced ampullary cancer cells patients bulky tumor opn infiltrating tams mif expression worst disease specific survival pubmed","probabilities":1.0,"Title":"Osteopontin-positive infiltrating tumor-associated macrophages in bulky ampullary cancer predict survival","Abstract":"PURPOSE: Tumor-associated macrophages (TAMs) promote cancer cell proliferation and distant metastases. Osteopontin (OPN) is overexpressed in several human cancer cells and in TAMs. Therefore, we set out to determine the role of OPN-expressing macrophages in cancer. RESULTS: In 100 ampullary cancers, diffuse cytoplasmic positivity for OPN was found in infiltrating TAMs in 36 patients and marginal TAMs in 32 patients; OPN(+) macrophages were absent in 32 patients. Expression patterns of OPN in TAMs were associated with pancreatic invasion, tumor stage, TNM stage, lymphovascular invasion and recurrence with peritoneal carcinomatosis. Patients were stratified according to a median tumor size of 2 cm. Patients with tumor sizes ≥2 cm and OPN(+) infiltrating TAMs had a poorer disease-specific survival rate than those with OPN(+) marginal TAMs. Macrophage-associated cytokine expression in ampullary cancer cells was also assessed; levels of macrophage migration inhibitory factor (MIF) in cancer cells were higher than in normal duodenal mucosa. EXPERIMENTAL DESIGN: Specimens from ampullary cancer patients at National Cheng Kung University Hospital were collected for immunohistochemistry. Plasma OPN was measured by enzyme-linked immunosorbent assay. Tumor and normal epithelial cells from fresh tissues were separated by laser-assisted microdissection for reverse-transcription polymerase chain reaction and quantitative real-time PCR analyses. CONCLUSIONS: Expression of OPN and location of TAMs in bulky ampullary cancer predict recurrence. In addition, cytoplasmic staining of MIF is enhanced in ampullary cancer cells. Patients with bulky tumor, OPN(+) infiltrating TAMs and MIF expression had a worst disease-specific survival.","Source":"PubMed","category":"ANIMAL","training_data":"Osteopontin-positive infiltrating tumor-associated macrophages in bulky ampullary cancer predict survival PURPOSE: Tumor-associated macrophages (TAMs) promote cancer cell proliferation and distant metastases. Osteopontin (OPN) is overexpressed in several human cancer cells and in TAMs. Therefore, we set out to determine the role of OPN-expressing macrophages in cancer. RESULTS: In 100 ampullary cancers, diffuse cytoplasmic positivity for OPN was found in infiltrating TAMs in 36 patients and marginal TAMs in 32 patients; OPN(+) macrophages were absent in 32 patients. Expression patterns of OPN in TAMs were associated with pancreatic invasion, tumor stage, TNM stage, lymphovascular invasion and recurrence with peritoneal carcinomatosis. Patients were stratified according to a median tumor size of 2 cm. Patients with tumor sizes ≥2 cm and OPN(+) infiltrating TAMs had a poorer disease-specific survival rate than those with OPN(+) marginal TAMs. Macrophage-associated cytokine expression in ampullary cancer cells was also assessed; levels of macrophage migration inhibitory factor (MIF) in cancer cells were higher than in normal duodenal mucosa. EXPERIMENTAL DESIGN: Specimens from ampullary cancer patients at National Cheng Kung University Hospital were collected for immunohistochemistry. Plasma OPN was measured by enzyme-linked immunosorbent assay. Tumor and normal epithelial cells from fresh tissues were separated by laser-assisted microdissection for reverse-transcription polymerase chain reaction and quantitative real-time PCR analyses. CONCLUSIONS: Expression of OPN and location of TAMs in bulky ampullary cancer predict recurrence. In addition, cytoplasmic staining of MIF is enhanced in ampullary cancer cells. Patients with bulky tumor, OPN(+) infiltrating TAMs and MIF expression had a worst disease-specific survival. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"novel antireflux metal stent palliation biliary malignancies pilot feasibility study video background antireflux stents prevent duodenal biliary reflux may improve biliary drainage prolong stent patency however use antireflux metal stents armss human biliary system reported objective evaluate safety efficacy armss palliation unresectable distal biliary malignancies design setting retrospective case series tertiary referral center patients august 2007 april 2009 total 23 patients unresectable nonhilar malignant biliary obstruction intervention endoscopic placement arms main outcome measurements technical success early complications follow stent patency patient survival results placement arms successful first attempt patients procedure related complications follow obtained 22 cases serum bilirubin level returned normal within 1 month stenting 20 patients six stent malfunctions occurred result tumor ingrowth 1 patient tumor overgrowth 2 patients stent migration 3 patients remaining patients free biliary symptoms death final follow median duration stent patency armss 14 months cumulative patency rates 3 6 12 months 95 74 56 respectively median survival patients 7 9 months range 1 14 months limitations small number patients single endoscopy center conclusions endoscopic insertion arms technically feasible safe effective patients distal malignant biliary obstruction impact armss prolonging stent patency life expectancy deserves randomized evaluation pubmed","probabilities":0.8684211,"Title":"A novel antireflux metal stent for the palliation of biliary malignancies: a pilot feasibility study (with video)","Abstract":"BACKGROUND: Antireflux stents that prevent duodenal biliary reflux may improve biliary drainage and prolong stent patency. However, the use of antireflux metal stents (ARMSs) in the human biliary system has not been reported. OBJECTIVE: To evaluate the safety and efficacy of ARMSs for the palliation of unresectable distal biliary malignancies. DESIGN AND SETTING: A retrospective case series in a tertiary referral center. PATIENTS: From August 2007 to April 2009, a total of 23 patients with unresectable nonhilar malignant biliary obstruction. INTERVENTION: Endoscopic placement of an ARMS. MAIN OUTCOME MEASUREMENTS: Technical success and early complications with follow-up of stent patency and patient survival. RESULTS: Placement of an ARMS was successful on the first attempt in all patients. There were no procedure-related complications. Follow-up was obtained in 22 cases. Serum bilirubin level returned to normal within 1 month of stenting in 20 patients. Six stent malfunctions occurred as a result of tumor ingrowth (1 patient), tumor overgrowth (2 patients), and stent migration (3 patients). The remaining patients were free of biliary symptoms until death or final follow-up. The median duration of stent patency of ARMSs was 14 months, with cumulative patency rates at 3, 6, and 12 months of 95%, 74%, and 56%, respectively. The median survival of the patients was 7.9 months (range, 1-14 months). LIMITATIONS: Small number of patients in single endoscopy center. CONCLUSIONS: Endoscopic insertion of an ARMS is technically feasible, safe, and effective in patients with distal malignant biliary obstruction. The impact of ARMSs in prolonging stent patency and life expectancy deserves further randomized evaluation.","Source":"PubMed","category":"HUMAN","training_data":"A novel antireflux metal stent for the palliation of biliary malignancies: a pilot feasibility study (with video) BACKGROUND: Antireflux stents that prevent duodenal biliary reflux may improve biliary drainage and prolong stent patency. However, the use of antireflux metal stents (ARMSs) in the human biliary system has not been reported. OBJECTIVE: To evaluate the safety and efficacy of ARMSs for the palliation of unresectable distal biliary malignancies. DESIGN AND SETTING: A retrospective case series in a tertiary referral center. PATIENTS: From August 2007 to April 2009, a total of 23 patients with unresectable nonhilar malignant biliary obstruction. INTERVENTION: Endoscopic placement of an ARMS. MAIN OUTCOME MEASUREMENTS: Technical success and early complications with follow-up of stent patency and patient survival. RESULTS: Placement of an ARMS was successful on the first attempt in all patients. There were no procedure-related complications. Follow-up was obtained in 22 cases. Serum bilirubin level returned to normal within 1 month of stenting in 20 patients. Six stent malfunctions occurred as a result of tumor ingrowth (1 patient), tumor overgrowth (2 patients), and stent migration (3 patients). The remaining patients were free of biliary symptoms until death or final follow-up. The median duration of stent patency of ARMSs was 14 months, with cumulative patency rates at 3, 6, and 12 months of 95%, 74%, and 56%, respectively. The median survival of the patients was 7.9 months (range, 1-14 months). LIMITATIONS: Small number of patients in single endoscopy center. CONCLUSIONS: Endoscopic insertion of an ARMS is technically feasible, safe, and effective in patients with distal malignant biliary obstruction. The impact of ARMSs in prolonging stent patency and life expectancy deserves further randomized evaluation. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pancreatoduodenectomy bile duct ampullary cancer pylorus preserving pancreatoduodenectomy become standard operation distal middle bile duct cancers bile duct cancer typically extends longitudinally invades vertically frequently metastasizes lymph nodes infiltrates perineural spaces presence residual cancer bile duct stump lymph node metastases significant prognostic factors negative surgical margins d2 lymph node dissection necessary curative resection clinical course portal vein resection bile duct cancer portal vein invasion better non resectable bile duct cancer portal vein resection therefore useful efficacy prophylactic portal vein resection unclear describe methods performing pylorus preserving pancreatoduodenectomy bile duct cancer pubmed","probabilities":0.9799733,"Title":"Pancreatoduodenectomy for bile duct and ampullary cancer","Abstract":"Pylorus-preserving pancreatoduodenectomy has become a standard operation for distal and middle bile duct cancers. Bile duct cancer typically extends longitudinally and invades vertically. It frequently metastasizes to the lymph nodes and infiltrates the perineural spaces. The presence of residual cancer in the bile duct stump and lymph node metastases are significant prognostic factors. Negative surgical margins and D2 lymph node dissection are necessary for curative resection. The clinical course after portal vein resection for bile duct cancer with portal vein invasion is better than that of non-resectable bile duct cancer. Portal vein resection can therefore be useful. The efficacy of prophylactic portal vein resection is unclear. We describe here our methods for performing pylorus-preserving pancreatoduodenectomy for bile duct cancer.","Source":"PubMed","category":"HUMAN","training_data":"Pancreatoduodenectomy for bile duct and ampullary cancer Pylorus-preserving pancreatoduodenectomy has become a standard operation for distal and middle bile duct cancers. Bile duct cancer typically extends longitudinally and invades vertically. It frequently metastasizes to the lymph nodes and infiltrates the perineural spaces. The presence of residual cancer in the bile duct stump and lymph node metastases are significant prognostic factors. Negative surgical margins and D2 lymph node dissection are necessary for curative resection. The clinical course after portal vein resection for bile duct cancer with portal vein invasion is better than that of non-resectable bile duct cancer. Portal vein resection can therefore be useful. The efficacy of prophylactic portal vein resection is unclear. We describe here our methods for performing pylorus-preserving pancreatoduodenectomy for bile duct cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"downregulation organic cation transporter 1 slc22a1 associated tumor progression reduced patient survival human cholangiocellular carcinoma cholangiocellular carcinoma cca primary hepatic malignancy derived cholangiocytes prognosis cca patients poor conventional chemotherapy proven ineffective improving long term patient survival rates organic cation transporters octs mediate transport broad spectrum endogenous substrates detoxification xenobiotics moreover octs considered responsible responsiveness towards platinum based chemotherapies currently data available regarding role octs cca therefore aim study investigate expression oct1 oct3 cca corresponding non neoplastic tumor surrounding tissue tst oct1 slc22a1 oct3 slc22a3 mrna expression measured primary human cca real time pcr n 27 protein expression determined western blot analysis immunohistochemistry data correlated clinicopathological parameters cca real time pcr demonstrated downregulation expression slc22a1 slc22a3 cca compared tst p 0 001 low slc22a1 expression associated worse patient survival p 0 05 downregulation slc22a1 significantly associated advanced cca stages since tumors low slc22a1 mrna expression presented larger tumor diameters p 0 02 significant differences tumor characteristics patient survival relation level slc22a3 expression western blot analysis immunohistochemistry confirmed downregulation oct1 oct3 protein levels cancerous tissue compared tst conclusion downregulation oct1 associated tumor progression worse overall patient survival rates stn","probabilities":0.8333333,"Title":"Downregulation Of Organic Cation Transporter 1 (Slc22A1) Is Associated With Tumor Progression And Reduced Patient Survival In Human Cholangiocellular Carcinoma","Abstract":"Cholangiocellular carcinoma (CCA) is a primary hepatic malignancy derived from cholangiocytes. The prognosis for CCA patients is very poor and conventional chemotherapy has been proven ineffective in improving long‑term patient survival rates. Organic cation transporters (OCTs) mediate the transport of a broad spectrum of endogenous substrates and the detoxification of xenobiotics. Moreover, OCTs are considered responsible for the responsiveness towards platinum‑based chemotherapies. Currently, there are no data available regarding the role of OCTs in CCA. Therefore, the aim of this study was to investigate the expression of OCT1 and OCT3 in CCA and the corresponding non-neoplastic tumor‑surrounding tissue (TST). OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human CCA by real-time PCR (n=27). Protein expression was determined by western blot analysis and immunohistochemistry. Data were correlated with the clinicopathological parameters of CCA. Real-time PCR demonstrated a downregulation of the expression of SLC22A1 and SLC22A3 in CCA, compared to that in TST (p<0.001). A low SLC22A1 expression was associated with a worse patient survival (p<0.05). The downregulation of SLC22A1 was significantly associated with advanced CCA stages, since tumors with a low SLC22A1 mRNA expression presented with larger tumor diameters (p=0.02). There were no significant differences in tumor characteristics or patient survival in relation to the level of SLC22A3 expression. Western blot analysis and immunohistochemistry confirmed the downregulation of OCT1 and OCT3 protein levels in cancerous tissue compared to those in TST. In conclusion, the downregulation of OCT1 is associated with tumor progression and worse overall patient survival rates.","Source":"STN","category":"HUMAN","training_data":"Downregulation Of Organic Cation Transporter 1 (Slc22A1) Is Associated With Tumor Progression And Reduced Patient Survival In Human Cholangiocellular Carcinoma Cholangiocellular carcinoma (CCA) is a primary hepatic malignancy derived from cholangiocytes. The prognosis for CCA patients is very poor and conventional chemotherapy has been proven ineffective in improving long‑term patient survival rates. Organic cation transporters (OCTs) mediate the transport of a broad spectrum of endogenous substrates and the detoxification of xenobiotics. Moreover, OCTs are considered responsible for the responsiveness towards platinum‑based chemotherapies. Currently, there are no data available regarding the role of OCTs in CCA. Therefore, the aim of this study was to investigate the expression of OCT1 and OCT3 in CCA and the corresponding non-neoplastic tumor‑surrounding tissue (TST). OCT1 (SLC22A1) and OCT3 (SLC22A3) mRNA expression was measured in primary human CCA by real-time PCR (n=27). Protein expression was determined by western blot analysis and immunohistochemistry. Data were correlated with the clinicopathological parameters of CCA. Real-time PCR demonstrated a downregulation of the expression of SLC22A1 and SLC22A3 in CCA, compared to that in TST (p<0.001). A low SLC22A1 expression was associated with a worse patient survival (p<0.05). The downregulation of SLC22A1 was significantly associated with advanced CCA stages, since tumors with a low SLC22A1 mRNA expression presented with larger tumor diameters (p=0.02). There were no significant differences in tumor characteristics or patient survival in relation to the level of SLC22A3 expression. Western blot analysis and immunohistochemistry confirmed the downregulation of OCT1 and OCT3 protein levels in cancerous tissue compared to those in TST. In conclusion, the downregulation of OCT1 is associated with tumor progression and worse overall patient survival rates. STN","prediction_labels":"HUMAN"},{"cleaned":"e2f1 e2f7 differentially regulate kpna2 promote development gallbladder cancer karyopherin alpha 2 kpna2 nuclear import factor elevated multiple cancers however molecular regulation transcriptional levels poorly understood found kpna2 significantly upregulated gallbladder cancer gbc increased levels correlated short survival patients gene knocking kpna2 inhibited tumor cell proliferation migration vitro well xenografted tumor development vivo typical transcription factor e2f1 associated dna binding partner dp1 bond promoter region kpna2 induced kpna2 expression contrast atypical transcription factor e2f7 competed dp1 blocked e2f1 induced kpna2 gene activation mutation dimerization residues e2f7 dna binding domain e2f1 abolished suppressive effects e2f7 kpna2 gene expression addition kpna2 mediated nuclear localization e2f1 e2f7 turn controlled kpna2 expression taken together data provided mechanistic insights divergently transcriptional regulation kpna2 thus pointing kpna2 potential target cancer therapy stn","probabilities":0.9467213,"Title":"E2F1 And E2F7 Differentially Regulate Kpna2 To Promote The Development Of Gallbladder Cancer","Abstract":"Karyopherin alpha 2 (KPNA2) is a nuclear import factor that is elevated in multiple cancers. However, its molecular regulation at the transcriptional levels is poorly understood. Here we found that KPNA2 was significantly upregulated in gallbladder cancer (GBC), and the increased levels were correlated with short survival of patients. Gene knocking down of KPNA2 inhibited tumor cell proliferation and migration in vitro as well as xenografted tumor development in vivo. A typical transcription factor E2F1 associated with its DNA-binding partner DP1 bond to the promoter region of KPNA2 and induced KPNA2 expression. In contrast, an atypical transcription factor E2F7 competed against DP1 and blocked E2F1-induced KPNA2 gene activation. Mutation of the dimerization residues of E2F7 or DNA-binding domain of E2F1 abolished the suppressive effects of E2F7 on KPNA2 gene expression. In addition, KPNA2 mediated nuclear localization of E2F1 and E2F7, where they in turn controlled KPNA2 expression. Taken together, our data provided mechanistic insights into divergently transcriptional regulation of KPNA2, thus pointing to KPNA2 as a potential target for cancer therapy.","Source":"STN","category":"ANIMAL","training_data":"E2F1 And E2F7 Differentially Regulate Kpna2 To Promote The Development Of Gallbladder Cancer Karyopherin alpha 2 (KPNA2) is a nuclear import factor that is elevated in multiple cancers. However, its molecular regulation at the transcriptional levels is poorly understood. Here we found that KPNA2 was significantly upregulated in gallbladder cancer (GBC), and the increased levels were correlated with short survival of patients. Gene knocking down of KPNA2 inhibited tumor cell proliferation and migration in vitro as well as xenografted tumor development in vivo. A typical transcription factor E2F1 associated with its DNA-binding partner DP1 bond to the promoter region of KPNA2 and induced KPNA2 expression. In contrast, an atypical transcription factor E2F7 competed against DP1 and blocked E2F1-induced KPNA2 gene activation. Mutation of the dimerization residues of E2F7 or DNA-binding domain of E2F1 abolished the suppressive effects of E2F7 on KPNA2 gene expression. In addition, KPNA2 mediated nuclear localization of E2F1 and E2F7, where they in turn controlled KPNA2 expression. Taken together, our data provided mechanistic insights into divergently transcriptional regulation of KPNA2, thus pointing to KPNA2 as a potential target for cancer therapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"common factors involved pathogenesis primary liver cancers meta analysis risk factors intrahepatic cholangiocarcinoma background aims well established risk factors intrahepatic cholangiocarcinoma biliary tract inflammation liver flukes present western countries patients although cirrhosis causes chronic liver disease implicated contribution risk factors cholangiocarcinoma unclear aims analyze emerging potential risk factors systematic examination case control series geographically diverse regions methods performed literature review meta analysis case control studies intrahepatic cholangiocarcinoma cirrhosis related risk factors tests heterogeneity publication bias sensitivity analyses performed overall odds ratio 95 confidence intervals calculated results eleven studies high low prevalence regions identified studies except evaluating cirrhosis diabetes obesity exhibited significant heterogeneity cirrhosis associated combined 22 92 95 ci 18 24 28 79 meta analysis estimated overall odds ratio 95 confidence intervals defined risk factors hepatitis b 5 10 2 91 8 95 hepatitis c 4 84 2 41 9 71 obesity 1 56 1 26 1 94 diabetes mellitus type ii 1 89 1 74 2 07 smoking 1 31 0 95 1 82 alcohol use 2 81 1 52 5 21 sensitivity analysis alter odds ratio risk factors except smoking evidence publication bias conclusions cirrhosis chronic hepatitis b c alcohol use diabetes obesity major risk factors intrahepatic cholangiocarcinoma data suggest common pathogenesis primary intrahepatic epithelial cancers pubmed","probabilities":0.9799733,"Title":"Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND & AIMS: Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions. METHODS: We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated. RESULTS: Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias. CONCLUSIONS: Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers.","Source":"PubMed","category":"HUMAN","training_data":"Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma BACKGROUND & AIMS: Well established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case-control series from geographically diverse regions. METHODS: We performed a literature review and meta-analysis of case-control studies on intrahepatic cholangiocarcinoma and cirrhosis and related risk factors. Tests of heterogeneity, publication bias and sensitivity analyses were performed and an overall odds ratio and 95% confidence intervals calculated. RESULTS: Eleven studies from both high and low prevalence regions were identified. All studies except those evaluating cirrhosis, diabetes, and obesity exhibited significant heterogeneity. Cirrhosis was associated with a combined OR of 22.92 (95% CI=18.24-28.79). Meta-analysis estimated the overall odds ratio (with 95% confidence intervals) for defined risk factors such as hepatitis B: 5.10 (2.91-8.95), hepatitis C: 4.84 (2.41-9.71), obesity: 1.56 (1.26-1.94), diabetes mellitus type II: 1.89 (1.74-2.07), smoking: 1.31 (0.95-1.82), and alcohol use: 2.81 (1.52-5.21). Sensitivity analysis did not alter the odds ratio for any risk factors except smoking and there was no evidence of publication bias. CONCLUSIONS: Cirrhosis, chronic hepatitis B and C, alcohol use, diabetes, and obesity are major risk factors for intrahepatic cholangiocarcinoma. These data suggest a common pathogenesis of primary intrahepatic epithelial cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"lymph node dissection resectable perihilar cholangiocarcinoma systematic review background perihilar cholangiocarcinoma usually unresectable time diagnosis patients candidates potential curative treatment patients prognosis strongly related negative resection margin lymph node status thus certain benchmark lymph node count necessary secure relevant lymph node recovery avoid understaging however required minimum number retrieved lymph nodes remains unclear perihilar cholangiocarcinoma 7th american joint committee cancer tumor nodes metastases edition increased requirement histologic examination lymph nodes perihilar cholangiocarcinoma patients 3 15 applicability recommendation appears difficult questionable therefore purpose systematic review evaluate number retrieved lymph nodes staging patients undergoing surgery perihilar cholangiocarcinoma methods medline embase cochrane library databases systematically screened december 2014 studies reporting number lymph node count perihilar cholangiocarcinoma included assessed eligibility results total 725 abstracts screened 20 studies included analysis comprising almost 4 000 patients cumulative median lymph node count 7 2 24 median lymph node count greater equal 15 reported 9 perihilar cholangiocarcinoma patients achieved extended lymphadenectomy subgroup analysis revealed median lymph node count 7 range 7 9 associated detection lymph node positive patients showed lowest risk understaging patients lymph node count greater equal 15 increase detection rate lymph node positive patients conclusions systematic analysis suggests lymph node count greater equal 7 adequate prognostic staging lymph node count greater equal 15 improve detection patients positive lymph nodes pubmed","probabilities":0.9799733,"Title":"Lymph node dissection in resectable perihilar cholangiocarcinoma: a systematic review","Abstract":"BACKGROUND: Perihilar cholangiocarcinoma is usually unresectable at the time of diagnosis. Only few patients are candidates for a potential curative treatment. For those patients, prognosis is strongly related to negative resection margin and lymph node status. Thus, a certain benchmark of lymph node count is necessary to secure relevant lymph node recovery and to avoid understaging. However, the required minimum number of retrieved lymph nodes remains unclear for perihilar cholangiocarcinoma. The 7th American Joint Committee on Cancer tumor, nodes, metastases edition increased the requirement for the histologic examination of lymph nodes in perihilar cholangiocarcinoma patients from 3 to 15. The applicability of such recommendation appears difficult and questionable. Therefore, the purpose of this systematic review is to evaluate the number of retrieved lymph nodes for staging of patients undergoing surgery for perihilar cholangiocarcinoma. METHODS: The MEDLINE, EMBASE, and The Cochrane Library databases were systematically screened up to December 2014. All studies reporting the number of lymph node count in perihilar cholangiocarcinoma were included and assessed for eligibility. RESULTS: A total of 725 abstracts were screened and 20 studies were included for analysis, comprising almost 4,000 patients. The cumulative median lymph node count was 7 (2 to 24). A median lymph node count greater than or equal to 15 was reported in 9% of perihilar cholangiocarcinoma patients and could only be achieved in extended lymphadenectomy. Subgroup analysis revealed a median lymph node count of 7 (range 7 to 9), which was associated with the detection of most lymph node positive patients and showed the lowest risk for understaging patients. Lymph node count greater than or equal to 15 did not increase detection rate of lymph node positive patients. CONCLUSIONS: This systematic analysis suggests that lymph node count greater than or equal to 7 is adequate for prognostic staging, while lymph node count greater than or equal to 15 does not improve detection of patients with positive lymph nodes.","Source":"PubMed","category":"HUMAN","training_data":"Lymph node dissection in resectable perihilar cholangiocarcinoma: a systematic review BACKGROUND: Perihilar cholangiocarcinoma is usually unresectable at the time of diagnosis. Only few patients are candidates for a potential curative treatment. For those patients, prognosis is strongly related to negative resection margin and lymph node status. Thus, a certain benchmark of lymph node count is necessary to secure relevant lymph node recovery and to avoid understaging. However, the required minimum number of retrieved lymph nodes remains unclear for perihilar cholangiocarcinoma. The 7th American Joint Committee on Cancer tumor, nodes, metastases edition increased the requirement for the histologic examination of lymph nodes in perihilar cholangiocarcinoma patients from 3 to 15. The applicability of such recommendation appears difficult and questionable. Therefore, the purpose of this systematic review is to evaluate the number of retrieved lymph nodes for staging of patients undergoing surgery for perihilar cholangiocarcinoma. METHODS: The MEDLINE, EMBASE, and The Cochrane Library databases were systematically screened up to December 2014. All studies reporting the number of lymph node count in perihilar cholangiocarcinoma were included and assessed for eligibility. RESULTS: A total of 725 abstracts were screened and 20 studies were included for analysis, comprising almost 4,000 patients. The cumulative median lymph node count was 7 (2 to 24). A median lymph node count greater than or equal to 15 was reported in 9% of perihilar cholangiocarcinoma patients and could only be achieved in extended lymphadenectomy. Subgroup analysis revealed a median lymph node count of 7 (range 7 to 9), which was associated with the detection of most lymph node positive patients and showed the lowest risk for understaging patients. Lymph node count greater than or equal to 15 did not increase detection rate of lymph node positive patients. CONCLUSIONS: This systematic analysis suggests that lymph node count greater than or equal to 7 is adequate for prognostic staging, while lymph node count greater than or equal to 15 does not improve detection of patients with positive lymph nodes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"identification transforming activity free fatty acid receptor 2 retroviral expression screening gallbladder cancer gbc highly fatal malignancy humans genetic alterations kras tp53 well overexpression erbb2 shown contribute development certain types gbc however many cases gbc harbor genetic changes transforming events awaiting discovery tried identify novel cancer promoting genes gbc use retroviral cdna expression library retroviral cdna expression library constructed surgically resected clinical specimen gbc used infect 3t3 fibroblasts focus formation assay cdna incorporated transformed foci rescued pcr one cdna found encode free fatty acid receptor 2 ffar2 g protein coupled receptor short chain fatty acids oncogenic potential ffar2 confirmed vitro focus formation assay evaluation cell growth soft agar well vivo tumorigenicity assay nude mice isolated ffar2 cdna sequence alterations suggesting upregulation ffar2 expression may contribute malignant transformation indeed quantitative rt pcr situ hybridization immunohistochemical analyses showed amount ffar2 mrna protein product increased digestive tract cancer specimens furthermore short chain fatty acids potentiated mitogenic action ffar2 3t3 cells data thus first time implicate ffar2 carcinogenesis digestive tract stn","probabilities":0.9467213,"Title":"Identification Of Transforming Activity Of Free Fatty Acid Receptor 2 By Retroviral Expression Screening","Abstract":"Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer-promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein-coupled receptor for short-chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT-PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short-chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract.","Source":"STN","category":"ANIMAL","training_data":"Identification Of Transforming Activity Of Free Fatty Acid Receptor 2 By Retroviral Expression Screening Gallbladder cancer (GBC) is a highly fatal malignancy in humans. Genetic alterations in KRAS or TP53 as well as overexpression of ERBB2 have been shown to contribute to the development of certain types of GBC. However, many cases of GBC do not harbor such genetic changes, with other transforming events awaiting discovery. We here tried to identify novel cancer-promoting genes in GBC, with the use of a retroviral cDNA expression library. A retroviral cDNA expression library was constructed from a surgically resected clinical specimen of GBC, and was used to infect 3T3 fibroblasts in a focus formation assay. cDNA incorporated into the transformed foci was rescued by PCR. One such cDNA was found to encode free fatty acid receptor 2 (FFAR2), a G protein-coupled receptor for short-chain fatty acids. The oncogenic potential of FFAR2 was confirmed both in vitro with the focus formation assay and by evaluation of cell growth in soft agar as well as in vivo with a tumorigenicity assay in nude mice. The isolated FFAR2 cDNA had no sequence alterations, suggesting that upregulation of FFAR2 expression may contribute to malignant transformation. Indeed, all of quantitative RT-PCR, in situ hybridization, and immunohistochemical analyses showed that the amount of FFAR2 mRNA and its protein product was increased in digestive tract cancer specimens. Furthermore, short-chain fatty acids potentiated the mitogenic action of FFAR2 in 3T3 cells. Our data thus, for the first time, implicate FFAR2 in carcinogenesis of the digestive tract. STN","prediction_labels":"ANIMAL"},{"cleaned":"targeting gallbladder carcinoma bone marrow derived stem cells therapeutic delivery vehicles myxoma virus background gallbladder carcinoma gbc high mortality rate requiring synergistic anti tumor management effective treatment myxoma virus myxv exhibits modest clinical value oncolytic potential narrow host tropism methods performed viral replication assays cell viability assays migration assays xenograft tumor models demonstrate bone marrow derived stem cells bmscs may enhance efficiency intravenous myxv delivery results examined permissiveness various gbc cell lines towards myxv infection found two supported single multiple rounds myxv replication leading oncolytic effect furthermore found bmscs exhibited tropism gbc cells within matrigel migration system bmscs failed affect growth gbc cells terms tumor volume survival time finally demonstrated vivo intravenous injection myxv infected bmscs significantly improves oncolytic effect myxv alone almost extent intratumoral injection myxv conclusion study indicates bmscs promising novel vehicle myxv clinically address gallbladder tumors stn","probabilities":0.9467213,"Title":"Targeting Gallbladder Carcinoma: Bone Marrow-Derived Stem Cells As Therapeutic Delivery Vehicles Of Myxoma Virus","Abstract":"Background: Gallbladder carcinoma (GBC) has a high mortality rate, requiring synergistic anti-tumor management for effective treatment. The myxoma virus (MYXV) exhibits a modest clinical value through its oncolytic potential and narrow host tropism. \r\n\r\n Methods: We performed viral replication assays, cell viability assays, migration assays, and xenograft tumor models to demonstrate that bone marrow-derived stem cells (BMSCs) may enhance efficiency of intravenous MYXV delivery. \r\n\r\n Results: We examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication, leading to an oncolytic effect. Furthermore, we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system. BMSCs failed to affect the growth of GBC cells, in terms of tumor volume and survival time. Finally, we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone, almost to the same extent as intratumoral injection of MYXV. \r\n\r\n Conclusion: This study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors.","Source":"STN","category":"ANIMAL","training_data":"Targeting Gallbladder Carcinoma: Bone Marrow-Derived Stem Cells As Therapeutic Delivery Vehicles Of Myxoma Virus Background: Gallbladder carcinoma (GBC) has a high mortality rate, requiring synergistic anti-tumor management for effective treatment. The myxoma virus (MYXV) exhibits a modest clinical value through its oncolytic potential and narrow host tropism. \r\n\r\n Methods: We performed viral replication assays, cell viability assays, migration assays, and xenograft tumor models to demonstrate that bone marrow-derived stem cells (BMSCs) may enhance efficiency of intravenous MYXV delivery. \r\n\r\n Results: We examined the permissiveness of various GBC cell lines towards MYXV infection and found two supported single and multiple rounds of MYXV replication, leading to an oncolytic effect. Furthermore, we found that BMSCs exhibited tropism for GBC cells within a Matrigel migration system. BMSCs failed to affect the growth of GBC cells, in terms of tumor volume and survival time. Finally, we demonstrated in vivo that intravenous injection of MYXV-infected BMSCs significantly improves the oncolytic effect of MYXV alone, almost to the same extent as intratumoral injection of MYXV. \r\n\r\n Conclusion: This study indicates that BMSCs are a promising novel vehicle for MYXV to clinically address gallbladder tumors. STN","prediction_labels":"ANIMAL"},{"cleaned":"upregulated nox1 expression gallbladder cancer associated fibroblasts predicts poor prognosis gallbladder cancer gbc lethal aggressive malignant neoplasm biliary tract potential prognostic markers therapeutic targets disease urgently required cancer associated fibroblasts cafs play key role tumorigenesis development cancer nicotinamide adenine dinucleotide phosphate oxidase 1 nox1 expression reported involved tumorigenesis useful tumor prognosis however nox1 expression stroma gbcs particularly gallbladder cancer associated fibroblasts gcafs prognostic significance gbc patients remains unclear present study nox1 expression stroma human gallbladder lesions vivo investigated well gcafs co cultures gbc sd gcafs vitro correlation clinicopathological parameters prognosis gbc patients evaluated results revealed nox1 expression significantly upregulated stroma gbcs compared precancerous benign lesions gallbladder nox1 expression localized gallbladder stromal fibroblasts expressing smooth muscle actin fibroblast secreted protein 1 furthermore observations confirmed fact nox1 expression upregulated gcafs determined affymetrix gene profile chip analysis reverse transcription quantitative pcr addition overexpression observed formed spheroids gbc sd gcaf co cultures immunohistochemistry western blotting vitro thus verified nox1 expression upregulated gcafs furthermore upregulated stromal nox1 expression correlated aggressive characteristics differentiation degree p 0 042 venous invasion p 0 041 resection methods p 0 002 lower survival rate p 0 025 log rank test patients gbc stromal nox1 expression p 0 047 independent prognostic factor overall survival rate patients gbc gbc patients upregulated nox1 expression gcafs poorer prognosis results revealed stromal nox1 may novel biomarker target may contribute discovery new tumor markers potential targeted therapeutics human gbcs stn","probabilities":1.0,"Title":"Upregulated Nox1 Expression In Gallbladder Cancer-Associated Fibroblasts Predicts A Poor Prognosis","Abstract":"Gallbladder cancer (GBC) is a lethal aggressive malignant neoplasm of the biliary tract. Potential prognostic markers and therapeutic targets for this disease are urgently required. Cancer‑associated fibroblasts (CAFs) play a key role in tumorigenesis and the development of cancer. Nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) expression has been reported to be involved in tumorigenesis and useful for tumor prognosis. However, NOX1 expression in the stroma of GBCs, particularly gallbladder cancer‑associated fibroblasts (GCAFs), and its prognostic significance in GBC patients remains unclear. In the present study, NOX1 expression in the stroma of human gallbladder lesions in vivo was investigated, as well as in GCAFs and co‑cultures of GBC‑SD+GCAFs in vitro, and their correlation with clinicopathological parameters and the prognosis of GBC patients were evaluated. The results revealed that NOX1 expression was significantly upregulated in the stroma of GBCs compared with precancerous and benign lesions of the gallbladder; NOX1 expression was localized to gallbladder stromal fibroblasts expressing α‑smooth muscle actin and fibroblast secreted protein‑1. Furthermore, these observations were confirmed by the fact that NOX1 expression was upregulated in GCAFs as determined by Affymetrix gene profile chip analysis and reverse transcription‑quantitative PCR. In addition, overexpression was observed in formed spheroids of GBC‑SD+GCAF co‑cultures by immunohistochemistry and western blotting in vitro. Thus, it was verified that NOX1 expression was upregulated in GCAFs. Furthermore, upregulated stromal NOX1 expression was correlated with aggressive characteristics such as differentiation degree (P=0.042), venous invasion (P=0.041), resection methods (P=0.002), and a lower survival rate (P=0.025, log‑rank test) of patients with GBC. Stromal NOX1 expression (P=0.047) was an independent prognostic factor for the overall survival rate of patients with GBC. GBC patients with upregulated NOX1 expression in GCAFs had a poorer prognosis. These results revealed that stromal NOX1 may be a novel biomarker and/or target, and may contribute to the discovery of new tumor markers and potential targeted therapeutics for human GBCs.","Source":"STN","category":"ANIMAL","training_data":"Upregulated Nox1 Expression In Gallbladder Cancer-Associated Fibroblasts Predicts A Poor Prognosis Gallbladder cancer (GBC) is a lethal aggressive malignant neoplasm of the biliary tract. Potential prognostic markers and therapeutic targets for this disease are urgently required. Cancer‑associated fibroblasts (CAFs) play a key role in tumorigenesis and the development of cancer. Nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) expression has been reported to be involved in tumorigenesis and useful for tumor prognosis. However, NOX1 expression in the stroma of GBCs, particularly gallbladder cancer‑associated fibroblasts (GCAFs), and its prognostic significance in GBC patients remains unclear. In the present study, NOX1 expression in the stroma of human gallbladder lesions in vivo was investigated, as well as in GCAFs and co‑cultures of GBC‑SD+GCAFs in vitro, and their correlation with clinicopathological parameters and the prognosis of GBC patients were evaluated. The results revealed that NOX1 expression was significantly upregulated in the stroma of GBCs compared with precancerous and benign lesions of the gallbladder; NOX1 expression was localized to gallbladder stromal fibroblasts expressing α‑smooth muscle actin and fibroblast secreted protein‑1. Furthermore, these observations were confirmed by the fact that NOX1 expression was upregulated in GCAFs as determined by Affymetrix gene profile chip analysis and reverse transcription‑quantitative PCR. In addition, overexpression was observed in formed spheroids of GBC‑SD+GCAF co‑cultures by immunohistochemistry and western blotting in vitro. Thus, it was verified that NOX1 expression was upregulated in GCAFs. Furthermore, upregulated stromal NOX1 expression was correlated with aggressive characteristics such as differentiation degree (P=0.042), venous invasion (P=0.041), resection methods (P=0.002), and a lower survival rate (P=0.025, log‑rank test) of patients with GBC. Stromal NOX1 expression (P=0.047) was an independent prognostic factor for the overall survival rate of patients with GBC. GBC patients with upregulated NOX1 expression in GCAFs had a poorer prognosis. These results revealed that stromal NOX1 may be a novel biomarker and/or target, and may contribute to the discovery of new tumor markers and potential targeted therapeutics for human GBCs. STN","prediction_labels":"ANIMAL"},{"cleaned":"epidemiological survey biomarkers hepatitis virus patients extrahepatic cholangiocarcinomas aim hepatitis virus b c hbv hcv suggested risk factors intrahepatic cholangiocarcinoma icc whether risk factors extrahepatic cholangiocarcinoma ecc disputed test biomarkers patients ecc elucidate relationship hbv hcv infection ecc risk conducted retrospective survey hepatitis virus markers patients ecc methods hospital based case control study conducted review prior infection hepatitis virus seroprevalence hepatitis virus markers patients ecc benign biliary disease bbd hbv x antigen hbxag detected tissues immunohistochemical staining results total 305 patients ecc 480 bbd enrolled study compared bbd patients ecc patients higher prevalence prior infection hbv 6 2 vs 2 3 chronic hbv infection 9 vs 1 9 overall seropositive rate hbv markers two groups 22 6 versus 6 p 0 01 hbxag detection 75 versus 26 p 0 001 seroprevalence anti hcv 4 3 eec patients 5 6 bbd patients significant difference conclusion high prevalence hbv biomarkers ecc strongly supports notion hbv infection may risk factor ecc high frequency hbxag expression suggests important role pathogenesis bile duct neoplasm pubmed","probabilities":0.88235295,"Title":"Epidemiological survey of biomarkers of hepatitis virus in patients with extrahepatic cholangiocarcinomas","Abstract":"AIM: Hepatitis virus B and C (HBV and HCV) are suggested to be risk factors for intrahepatic cholangiocarcinoma (ICC), but whether they are risk factors for extrahepatic cholangiocarcinoma (ECC) is disputed. To test the biomarkers in patients with ECC and further elucidate the relationship of HBV or HCV infection with ECC risk, we conducted a retrospective survey on hepatitis virus markers in patients with ECC. METHODS: A hospital-based case-control study was conducted to review prior infection with hepatitis virus and the seroprevalence of hepatitis virus markers in the patients with ECC or with benign biliary disease (BBD). HBV X antigen (HBxAg) was detected in the tissues by immunohistochemical staining. RESULTS: A total of 305 patients with ECC and 480 with BBD were enrolled in this study. Compared with BBD patients, ECC patients had a higher prevalence of prior infection with HBV (6.2 vs 2.3%) and chronic HBV infection (9 vs 1.9%). The overall seropositive rate for HBV markers in the two groups was 22.6 versus 6% (P < 0.01) and for HBxAg detection it was 75 versus 26% (P < 0.001). The seroprevalence of anti-HCV was 4.3% in the EEC patients and 5.6% in BBD patients with no significant difference between them. CONCLUSION: The high prevalence of HBV biomarkers in ECC strongly supports the notion that HBV infection may be a risk factor for ECC. The high frequency of HBxAg expression suggests its important role in the pathogenesis of bile duct neoplasm.","Source":"PubMed","category":"HUMAN","training_data":"Epidemiological survey of biomarkers of hepatitis virus in patients with extrahepatic cholangiocarcinomas AIM: Hepatitis virus B and C (HBV and HCV) are suggested to be risk factors for intrahepatic cholangiocarcinoma (ICC), but whether they are risk factors for extrahepatic cholangiocarcinoma (ECC) is disputed. To test the biomarkers in patients with ECC and further elucidate the relationship of HBV or HCV infection with ECC risk, we conducted a retrospective survey on hepatitis virus markers in patients with ECC. METHODS: A hospital-based case-control study was conducted to review prior infection with hepatitis virus and the seroprevalence of hepatitis virus markers in the patients with ECC or with benign biliary disease (BBD). HBV X antigen (HBxAg) was detected in the tissues by immunohistochemical staining. RESULTS: A total of 305 patients with ECC and 480 with BBD were enrolled in this study. Compared with BBD patients, ECC patients had a higher prevalence of prior infection with HBV (6.2 vs 2.3%) and chronic HBV infection (9 vs 1.9%). The overall seropositive rate for HBV markers in the two groups was 22.6 versus 6% (P < 0.01) and for HBxAg detection it was 75 versus 26% (P < 0.001). The seroprevalence of anti-HCV was 4.3% in the EEC patients and 5.6% in BBD patients with no significant difference between them. CONCLUSION: The high prevalence of HBV biomarkers in ECC strongly supports the notion that HBV infection may be a risk factor for ECC. The high frequency of HBxAg expression suggests its important role in the pathogenesis of bile duct neoplasm. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact portal vein resection oncologic long term outcome patients hilar cholangiocarcinoma background liver resection lr hilar cholangiocarcinoma hca remains challenging occurrence unanticipated vascular longitudinal bile duct invasion operative strategies achieve negative resection margins vary benefit routine portal vein resection pvr discussed controversially methods data 60 consecutive patients underwent lr hca analyzed twenty one patients 35 0 underwent lr plus pvr 39 65 0 lr clinicopathologic data evaluated use uni multivariate analyses results majority resections performed bismuth corlette type iii iv tumors 97 3 hepatectomy involved trisectionectomies 41 patients 68 3 r1 resection margin status identified adverse prognosis factor survival hazard ratio 3 61 p 003 pvr increased perioperative morbidity p 04 90 day mortality rate comparable groups p 70 negative resection margin status similar groups p 70 lymph node clearance equal p 86 pvr associated beneficial long term outcome 5 year disease free survival comparable lr 17 8 vs lr plus pvr 20 0 p 89 lr 10 6 vs lr plus pvr 21 4 p 63 pvr prognostic factor tumor dependent disease free survival hazard ratio 0 64 p 26 hazard ratio 0 76 p 47 conclusion presented data indicate simultaneous pvr beneficial impact oncologic long term outcome patients undergoing lr hca increases perioperative morbidity recommendation routine application given pubmed","probabilities":0.9799733,"Title":"Impact of portal vein resection on oncologic long-term outcome in patients with hilar cholangiocarcinoma","Abstract":"BACKGROUND: Liver resection (LR) for hilar cholangiocarcinoma (HCA) remains challenging because of the occurrence of unanticipated vascular and longitudinal bile duct invasion. Operative strategies to achieve negative resection margins vary, and the benefit of routine portal vein resection (PVR) is discussed controversially. METHODS: The data of 60 consecutive patients who underwent LR for HCA were analyzed. Twenty-one patients (35.0%) underwent LR plus PVR and 39 (65.0%) LR only. Clinicopathologic data were evaluated by the use of uni- and multivariate analyses. RESULTS: The majority of resections was performed for Bismuth-Corlette type III/IV tumors (97.3%). Hepatectomy involved trisectionectomies in 41 patients (68.3%). R1 resection margin status was identified as adverse prognosis factor for survival (hazard ratio 3.61; P = .003). PVR increased the perioperative morbidity (P = .04). The 90-day mortality rate was comparable between both groups (P = .70). Negative resection margin status was similar between groups (P = .70). The lymph node clearance was equal (P = .86). PVR was not associated with a beneficial long-term outcome, the 5-year and disease-free survival were comparable (LR only 17.8% vs LR plus PVR 20.0% [P = .89] and LR only 10.6% vs LR plus PVR 21.4% [P = .63]). PVR was no prognostic factor for tumor-dependent or disease-free survival (hazard ratio 0.64; P = .26 and hazard ratio 0.76; P = .47). CONCLUSION: The presented data indicate that simultaneous PVR has no beneficial impact on oncologic long-term outcome in patients undergoing LR for HCA. Because it increases the perioperative morbidity, a recommendation for routine application cannot be given.","Source":"PubMed","category":"HUMAN","training_data":"Impact of portal vein resection on oncologic long-term outcome in patients with hilar cholangiocarcinoma BACKGROUND: Liver resection (LR) for hilar cholangiocarcinoma (HCA) remains challenging because of the occurrence of unanticipated vascular and longitudinal bile duct invasion. Operative strategies to achieve negative resection margins vary, and the benefit of routine portal vein resection (PVR) is discussed controversially. METHODS: The data of 60 consecutive patients who underwent LR for HCA were analyzed. Twenty-one patients (35.0%) underwent LR plus PVR and 39 (65.0%) LR only. Clinicopathologic data were evaluated by the use of uni- and multivariate analyses. RESULTS: The majority of resections was performed for Bismuth-Corlette type III/IV tumors (97.3%). Hepatectomy involved trisectionectomies in 41 patients (68.3%). R1 resection margin status was identified as adverse prognosis factor for survival (hazard ratio 3.61; P = .003). PVR increased the perioperative morbidity (P = .04). The 90-day mortality rate was comparable between both groups (P = .70). Negative resection margin status was similar between groups (P = .70). The lymph node clearance was equal (P = .86). PVR was not associated with a beneficial long-term outcome, the 5-year and disease-free survival were comparable (LR only 17.8% vs LR plus PVR 20.0% [P = .89] and LR only 10.6% vs LR plus PVR 21.4% [P = .63]). PVR was no prognostic factor for tumor-dependent or disease-free survival (hazard ratio 0.64; P = .26 and hazard ratio 0.76; P = .47). CONCLUSION: The presented data indicate that simultaneous PVR has no beneficial impact on oncologic long-term outcome in patients undergoing LR for HCA. Because it increases the perioperative morbidity, a recommendation for routine application cannot be given. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tgr5 promotes cholangiocarcinoma interacting mortalin takeda g protein receptor 5 tgr5 g protein coupled receptor gpcr activated bile acids mortalin multipotent chaperone hsp70 family present study tgr5 detected immunohistochemistry ihc extrahepatic cholangiocarcinoma ecc specimens tgr5 expression ecc tissues adjacent tissues compared vitro tgr5 overexpressed knocked human intrahepatic cholangiocarcinoma icc cell line rbe human extrahepatic cholangiocarcinoma ecc cell line qbc 939 observe effects biological behavior cholangiocarcinoma cc cells including proliferation apoptosis migration vivo xenograft model constructed explore role tgr5 cc growth proteins interacted tgr5 screened using immunoprecipitation spectrometry approach identified protein regulated investigate contribution cc growth present study demonstrated tgr5 highly expressed cc tissues strong tgr5 expression may indicate high malignancy cc furthermore tgr5 promotes cc cell proliferation migration apoptosis resistance tgr5 boosts cc growth vivo addition tgr5 combines mortalin regulates mortalin expression cc cell line mortalin participates tgr5 induced increase cc cell proliferation conclusion tgr5 clinical significance based implications degree malignancy patients cc mortalin may downstream component regulated tgr5 tgr5 promotes cholangiocarcinoma least partially interacting mortalin upregulating expression tgr5 mortalin positive regulators may serve potential therapeutic targets cc stn","probabilities":0.9467213,"Title":"Tgr5 Promotes Cholangiocarcinoma By Interacting With Mortalin","Abstract":"Takeda-G-protein-receptor-5 (TGR5) is a G-protein-coupled receptor (GPCR) activated by bile acids, and mortalin is a multipotent chaperone of the HSP70 family. In the present study, TGR5 was detected by immunohistochemistry (IHC) in extrahepatic cholangiocarcinoma (ECC) specimens, and TGR5 expression in ECC tissues and adjacent tissues was compared. In vitro TGR5 was overexpressed and knocked down in human intrahepatic cholangiocarcinoma (ICC) cell line RBE and human extrahepatic cholangiocarcinoma (ECC) cell line QBC-939 to observe its effects on the biological behavior of cholangiocarcinoma (CC) cells, including proliferation, apoptosis and migration. In vivo xenograft model was constructed to explore the role of TGR5 in CC growth. Proteins that interacted with TGR5 were screened using an immunoprecipitation spectrometry approach, and the identified protein was down-regulated to investigate its contribution to CC growth. The present study demonstrated that TGR5 is highly expressed in CC tissues, and strong TGR5 expression may indicate high malignancy in CC. Furthermore, TGR5 promotes CC cell proliferation, migration, and apoptosis resistance. TGR5 boosts CC growth in vivo. In addition, TGR5 combines with mortalin and regulates mortalin expression in the CC cell line. Mortalin participates in the TGR5-induced increase in CC cell proliferation. In conclusion, TGR5 is of clinical significance based on its implications for the degree of malignancy in patients with CC. Mortalin may be a downstream component regulated by TGR5, and TGR5 promotes cholangiocarcinoma at least partially by interacting with mortalin and upregulating its expression. Both TGR5 and mortalin are positive regulators, and may serve as potential therapeutic targets for CC.","Source":"STN","category":"ANIMAL","training_data":"Tgr5 Promotes Cholangiocarcinoma By Interacting With Mortalin Takeda-G-protein-receptor-5 (TGR5) is a G-protein-coupled receptor (GPCR) activated by bile acids, and mortalin is a multipotent chaperone of the HSP70 family. In the present study, TGR5 was detected by immunohistochemistry (IHC) in extrahepatic cholangiocarcinoma (ECC) specimens, and TGR5 expression in ECC tissues and adjacent tissues was compared. In vitro TGR5 was overexpressed and knocked down in human intrahepatic cholangiocarcinoma (ICC) cell line RBE and human extrahepatic cholangiocarcinoma (ECC) cell line QBC-939 to observe its effects on the biological behavior of cholangiocarcinoma (CC) cells, including proliferation, apoptosis and migration. In vivo xenograft model was constructed to explore the role of TGR5 in CC growth. Proteins that interacted with TGR5 were screened using an immunoprecipitation spectrometry approach, and the identified protein was down-regulated to investigate its contribution to CC growth. The present study demonstrated that TGR5 is highly expressed in CC tissues, and strong TGR5 expression may indicate high malignancy in CC. Furthermore, TGR5 promotes CC cell proliferation, migration, and apoptosis resistance. TGR5 boosts CC growth in vivo. In addition, TGR5 combines with mortalin and regulates mortalin expression in the CC cell line. Mortalin participates in the TGR5-induced increase in CC cell proliferation. In conclusion, TGR5 is of clinical significance based on its implications for the degree of malignancy in patients with CC. Mortalin may be a downstream component regulated by TGR5, and TGR5 promotes cholangiocarcinoma at least partially by interacting with mortalin and upregulating its expression. Both TGR5 and mortalin are positive regulators, and may serve as potential therapeutic targets for CC. STN","prediction_labels":"ANIMAL"},{"cleaned":"clinicopathological prognostic significance yes associated protein expression hepatocellular carcinoma hepatic cholangiocarcinoma hepatocellular carcinoma hcc hepatic cholangiocarcinoma cc aggressive malignancies poor prognosis humans hepatic cholangiocarcinoma cc exhibits greater malignant behaviour yes associated protein yap important downstream target hippo signalling pathway oncogene plays vital role occurrence development tumours study focuses clinical significance yap protein expression hcc cc furthermore sought explore different survival rates hcc cc total 137 patients hcc 122 cc resection evaluated immunohistochemistry expression yap results showed positive expression rates yap frequently noted cc 67 2 82 122 hcc 56 9 78 137 p 0 024 high yap expression hcc cc significantly associated tumour size p 0 001 p 0 019 respectively liver cirrhosis p 0 002 p 0 009 respectively vascular invasion p 0 047 p 0 018 respectively multiplicity p 0 019 p 0 015 respectively intrahepatic metastasis p 0 015 p 0 047 respectively importantly recurrence free survival disease specific survival rates lower cc high yap expression hcc high yap expression p 0 001 p 0 001 respectively overall high yap expression frequently found cc hcc yap overexpression associated poor survival rates patients hcc cc targeting yap treatment requires prospective investigations larger patient populations pubmed","probabilities":0.9799733,"Title":"Clinicopathological and prognostic significance of Yes-associated protein expression in hepatocellular carcinoma and hepatic cholangiocarcinoma","Abstract":"Hepatocellular carcinoma (HCC) and hepatic cholangiocarcinoma (CC) are the most aggressive malignancies with a poor prognosis in humans, and hepatic cholangiocarcinoma (CC) exhibits greater malignant behaviour. Yes-associated protein (YAP) is an important downstream target of the Hippo signalling pathway. As an oncogene, it plays a vital role in the occurrence and development of tumours. Our study focuses on the clinical significance of YAP protein expression in HCC and CC. Furthermore, we sought to explore the different survival rates between HCC and CC. A total of 137 patients with HCC and 122 with CC after resection were evaluated by immunohistochemistry for the expression of YAP. Our results showed that positive expression rates of YAP were more frequently noted in CC 67.2 % (82/122) than in HCC 56.9 % (78/137) (P = 0.024). High YAP expression in HCC and CC was significantly associated with tumour size (P < 0.001 and P = 0.019, respectively), liver cirrhosis (P = 0.002 and P = 0.009, respectively), vascular invasion (P = 0.047 and P = 0.018, respectively), multiplicity (P = 0.019 and P = 0.015, respectively), and intrahepatic metastasis (P = 0.015 and P = 0.047, respectively). Importantly, recurrence-free survival and disease-specific survival rates were lower in CC with high YAP expression than in HCC with high YAP expression (P < 0.001 and P < 0.001, respectively). Overall, high YAP expression was more frequently found in CC than in HCC, and YAP overexpression was associated with poor survival rates in patients with HCC and CC. Targeting YAP treatment requires further prospective investigations in larger patient populations.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological and prognostic significance of Yes-associated protein expression in hepatocellular carcinoma and hepatic cholangiocarcinoma Hepatocellular carcinoma (HCC) and hepatic cholangiocarcinoma (CC) are the most aggressive malignancies with a poor prognosis in humans, and hepatic cholangiocarcinoma (CC) exhibits greater malignant behaviour. Yes-associated protein (YAP) is an important downstream target of the Hippo signalling pathway. As an oncogene, it plays a vital role in the occurrence and development of tumours. Our study focuses on the clinical significance of YAP protein expression in HCC and CC. Furthermore, we sought to explore the different survival rates between HCC and CC. A total of 137 patients with HCC and 122 with CC after resection were evaluated by immunohistochemistry for the expression of YAP. Our results showed that positive expression rates of YAP were more frequently noted in CC 67.2 % (82/122) than in HCC 56.9 % (78/137) (P = 0.024). High YAP expression in HCC and CC was significantly associated with tumour size (P < 0.001 and P = 0.019, respectively), liver cirrhosis (P = 0.002 and P = 0.009, respectively), vascular invasion (P = 0.047 and P = 0.018, respectively), multiplicity (P = 0.019 and P = 0.015, respectively), and intrahepatic metastasis (P = 0.015 and P = 0.047, respectively). Importantly, recurrence-free survival and disease-specific survival rates were lower in CC with high YAP expression than in HCC with high YAP expression (P < 0.001 and P < 0.001, respectively). Overall, high YAP expression was more frequently found in CC than in HCC, and YAP overexpression was associated with poor survival rates in patients with HCC and CC. Targeting YAP treatment requires further prospective investigations in larger patient populations. PubMed","prediction_labels":"HUMAN"},{"cleaned":"limitations standard clinicopathologic features accurately risk stratify prognosis resection intrahepatic cholangiocarcinoma background ability provide accurate prognostic data hepatectomy intrahepatic cholangiocarcinoma icc remains poor sought develop validate nomogram predict survival well investigate clinical implications underestimating patients risk recurrence methods patients undergoing curative intent resection icc 1990 2015 14 major hepatobiliary centers included variables significant multivariable analysis used construct nomogram predict disease free survival dfs nomogram assigned score variable included model calculated risk recurrence results eight hundred ninety seven patients included analytic cohort multivariable cox regression analysis tumor size 5 cm hr 1 98 95 ci 1 44 2 13 p 0 001 multifocal icc hr 1 64 95 ci 1 32 2 03 p 0 001 lymph node metastasis hr 1 63 95 ci 1 25 2 11 p 0 001 poorly differentiated tumor grade hr 1 50 95 ci 1 21 1 89 p 0 001 periductal infiltrating type pi morphology hr 1 42 95 ci 1 09 1 83 p 0 008 independent adverse risk factors associated decreased dfs harrell c index nomogram 0 633 n 5000 bootstrapping resamples plot comparing predicted actuarial dfs demonstrated good calibration model subset patients n 282 dfs worse predicted predicted dfs actuarial dfs 6 months moreover underestimation recurrence risk common among patients clinicopathologic features traditionally considered favorable conclusion nomogram based standard clinicopathologic characteristics suboptimal ability predict accurately risk recurrence among patients icc curative intent liver resection particularly risk underestimating patient risk recurrence highest among patients historically favorable characteristics one third patients recurred 6 months earlier dfs predicted nomogram pubmed","probabilities":0.9799733,"Title":"The Limitations of Standard Clinicopathologic Features to Accurately Risk-Stratify Prognosis after Resection of Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND: The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence. METHODS: Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence. RESULTS: Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09-1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS - Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered \"favorable.\" CONCLUSION: A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram.","Source":"PubMed","category":"HUMAN","training_data":"The Limitations of Standard Clinicopathologic Features to Accurately Risk-Stratify Prognosis after Resection of Intrahepatic Cholangiocarcinoma BACKGROUND: The ability to provide accurate prognostic data after hepatectomy for intrahepatic cholangiocarcinoma (ICC) remains poor. We sought to develop and validate a nomogram to predict survival, as well as investigate the clinical implications of underestimating patients' risk of recurrence. METHODS: Patients undergoing curative-intent resection of ICC between 1990 and 2015 at 14 major hepatobiliary centers were included. Variables significant on multivariable analysis were used to construct a nomogram to predict disease-free survival (DFS). The nomogram assigned a score to each variable included in the model and calculated the risk of recurrence. RESULTS: Eight hundred ninety-seven patients are included in the analytic cohort. On multivariable Cox regression analysis, tumor size > 5 cm (HR 1.98, 95% CI 1.44-2.13; p < 0.001), multifocal ICC (HR 1.64, 95% CI 1.32-2.03; p < 0.001), lymph node metastasis (HR 1.63, 95% CI 1.25-2.11; p < 0.001), poorly differentiated tumor grade (HR 1.50, 95% CI 1.21-1.89; p < 0.001), and periductal infiltrating type (PI) morphology (HR 1.42, 95% CI 1.09-1.83; p = 0.008) were independent adverse risk factors associated with decreased DFS. The Harrell's c-index for the nomogram was 0.633 (with n = 5000 bootstrapping resamples) and the plot comparing predicted and actuarial DFS demonstrated a good calibration of the model. A subset of patients (n = 282) had a DFS worse than predicted (ΔPredicted DFS - Actuarial DFS > 6 months). Moreover, underestimation of a recurrence risk was more common among patients with clinicopathologic features traditionally considered \"favorable.\" CONCLUSION: A nomogram based on standard clinicopathologic characteristics was suboptimal in its ability to predict accurately risk of recurrence among patients with ICC after curative-intent liver resection. Particularly, the risk of underestimating patient risk of recurrence was highest among patients with historically favorable characteristics. Over one third of patients recurred > 6 months earlier than the DFS predicted by the nomogram. PubMed","prediction_labels":"HUMAN"},{"cleaned":"combined photodynamic therapy systemic chemotherapy unresectable cholangiocarcinoma background chemotherapy gemcitabine cisplatin current standard patients unresectable cholangiocarcinoma local photodynamic therapy also demonstrated benefit patients extrahepatic cholangiocarcinoma aim evaluate benefit photodynamic therapy combination systemic chemotherapy advanced extrahepatic cholangiocarcinoma methods three hundred fifty three patients diagnosed cholangiocarcinoma 2004 2016 treated university hospital bonn germany 96 suffering unresectable extrahepatic cholangiocarcinoma included patients stratified according treatment combination photodynamic therapy chemotherapy 36 patients photodynamic therapy alone 34 patients chemotherapy alone 26 patients results combined photodynamic therapy chemotherapy resulted significantly longer overall survival chemotherapy alone p 0 022 median survival 20 months combination group 95 ci 16 38 23 62 15 months photodynamic alone group 95 ci 10 02 19 98 10 months chemotherapy alone group 95 ci 8 45 11 55 multivariate analysis combination therapy photodynamic therapy alone hr 0 41 95 ci 0 22 0 77 p 0 006 metal stenting radiofrequency ablation independent predictors longer survival conclusions combination photodynamic therapy chemotherapy well tolerated resulted significantly longer survival chemotherapy alone application photodynamic therapy significantly correlated longer survival demonstrating benefit advanced cholangiocarcinoma thus photodynamic therapy considered therapeutic decision making advanced cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Combined photodynamic therapy with systemic chemotherapy for unresectable cholangiocarcinoma","Abstract":"BACKGROUND: Chemotherapy with gemcitabine and cisplatin is the current standard for patients with unresectable cholangiocarcinoma. Local photodynamic therapy has also demonstrated benefit in patients with extrahepatic cholangiocarcinoma. AIM: To evaluate the benefit of photodynamic therapy in combination with systemic chemotherapy in advanced extrahepatic cholangiocarcinoma. METHODS: Three hundred and fifty-three patients diagnosed with cholangiocarcinoma between 2004 and 2016 were treated at the University Hospital of Bonn, Germany. Of these, 96 suffering from unresectable extrahepatic cholangiocarcinoma were included. Patients were stratified according to treatment: combination photodynamic therapy and chemotherapy (36 patients), photodynamic therapy alone (34 patients), and chemotherapy alone (26 patients). RESULTS: Combined photodynamic therapy with chemotherapy resulted in significantly longer overall survival than chemotherapy alone (P = 0.022). Median survival was 20 months in the combination group (95% CI: 16.38-23.62), 15 months in the photodynamic alone group (95% CI: 10.02-19.98) and 10 months in the chemotherapy alone group (95% CI: 8.45-11.55). In multivariate analysis, combination therapy and photodynamic therapy alone (HR: 0.41, 95% CI: 0.22-0.77, P = 0.006), metal stenting, and radiofrequency ablation were independent predictors of longer survival. CONCLUSIONS: Combination photodynamic therapy and chemotherapy was well tolerated and resulted in significantly longer survival than chemotherapy alone. Application of photodynamic therapy significantly correlated with longer survival, demonstrating benefit in advanced cholangiocarcinoma. Thus, photodynamic therapy should be considered during therapeutic decision making in advanced cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Combined photodynamic therapy with systemic chemotherapy for unresectable cholangiocarcinoma BACKGROUND: Chemotherapy with gemcitabine and cisplatin is the current standard for patients with unresectable cholangiocarcinoma. Local photodynamic therapy has also demonstrated benefit in patients with extrahepatic cholangiocarcinoma. AIM: To evaluate the benefit of photodynamic therapy in combination with systemic chemotherapy in advanced extrahepatic cholangiocarcinoma. METHODS: Three hundred and fifty-three patients diagnosed with cholangiocarcinoma between 2004 and 2016 were treated at the University Hospital of Bonn, Germany. Of these, 96 suffering from unresectable extrahepatic cholangiocarcinoma were included. Patients were stratified according to treatment: combination photodynamic therapy and chemotherapy (36 patients), photodynamic therapy alone (34 patients), and chemotherapy alone (26 patients). RESULTS: Combined photodynamic therapy with chemotherapy resulted in significantly longer overall survival than chemotherapy alone (P = 0.022). Median survival was 20 months in the combination group (95% CI: 16.38-23.62), 15 months in the photodynamic alone group (95% CI: 10.02-19.98) and 10 months in the chemotherapy alone group (95% CI: 8.45-11.55). In multivariate analysis, combination therapy and photodynamic therapy alone (HR: 0.41, 95% CI: 0.22-0.77, P = 0.006), metal stenting, and radiofrequency ablation were independent predictors of longer survival. CONCLUSIONS: Combination photodynamic therapy and chemotherapy was well tolerated and resulted in significantly longer survival than chemotherapy alone. Application of photodynamic therapy significantly correlated with longer survival, demonstrating benefit in advanced cholangiocarcinoma. Thus, photodynamic therapy should be considered during therapeutic decision making in advanced cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"excess adiposity gastrointestinal cancer background excess adiposity risk factor incidence several gastrointestinal cancers unclear epidemiological observations translate clinical practice methods critical appraisals updated analyses published systematic reviews undertaken quantify cancer risk associations better assess impact weight reducing strategies surgical non surgical cancer prevention results conclusion large volume evidence demonstrates body mass index bmi approximation general adiposity risk factor development oesophageal adenocarcinoma colorectal hepatocellular gallbladder pancreatic cancers smaller volume evidence demonstrates indices increased central adiposity waist circumference associated increased risk oesophageal adenocarcinoma colorectal cancer indices necessarily better predictors risk compared bmi several biological mechanisms may explain associations hypothesis several caveats weaknesses data convincingly demonstrate significant reductions risk gastrointestinal cancers following weight reducing strategies turn many methodological pitfalls literature prevent conclusive interpretation lack robust intermediary obesity related biomarkers additional unresolved challenge prevention trials novel underpinning mechanisms example local ectopic fat accurate methods measure intermediaries sought explored optimistic research strategies future pubmed","probabilities":0.9799733,"Title":"Excess adiposity and gastrointestinal cancer","Abstract":"BACKGROUND: Excess adiposity is a risk factor for incidence of several gastrointestinal cancers, but it is unclear how these epidemiological observations translate into clinical practice. METHODS: Critical appraisals and updated analyses of published systematic reviews were undertaken to quantify cancer risk associations better and to assess the impact of weight-reducing strategies (surgical and non-surgical) on cancer prevention. RESULTS AND CONCLUSION: A large volume of evidence demonstrates that body mass index (BMI), as an approximation for general adiposity, is a risk factor for the development of oesophageal adenocarcinoma, and colorectal, hepatocellular, gallbladder and pancreatic cancers. A smaller volume of evidence demonstrates that indices of increased central adiposity (such as waist circumference) are associated with increased risk of oesophageal adenocarcinoma and colorectal cancer, but these indices are not necessarily better predictors of risk compared with BMI. Several biological mechanisms may explain these associations but each hypothesis has several caveats and weaknesses. There are few data that convincingly demonstrate significant reductions in risk of gastrointestinal cancers following weight-reducing strategies. In turn, there are many methodological pitfalls in this literature, which prevent conclusive interpretation. The lack of robust intermediary obesity-related biomarkers is an additional unresolved challenge for prevention trials. Novel underpinning mechanisms (for example, local ectopic fat) and more accurate methods to measure these intermediaries are sought and explored as the most optimistic research strategies for the future.","Source":"PubMed","category":"HUMAN","training_data":"Excess adiposity and gastrointestinal cancer BACKGROUND: Excess adiposity is a risk factor for incidence of several gastrointestinal cancers, but it is unclear how these epidemiological observations translate into clinical practice. METHODS: Critical appraisals and updated analyses of published systematic reviews were undertaken to quantify cancer risk associations better and to assess the impact of weight-reducing strategies (surgical and non-surgical) on cancer prevention. RESULTS AND CONCLUSION: A large volume of evidence demonstrates that body mass index (BMI), as an approximation for general adiposity, is a risk factor for the development of oesophageal adenocarcinoma, and colorectal, hepatocellular, gallbladder and pancreatic cancers. A smaller volume of evidence demonstrates that indices of increased central adiposity (such as waist circumference) are associated with increased risk of oesophageal adenocarcinoma and colorectal cancer, but these indices are not necessarily better predictors of risk compared with BMI. Several biological mechanisms may explain these associations but each hypothesis has several caveats and weaknesses. There are few data that convincingly demonstrate significant reductions in risk of gastrointestinal cancers following weight-reducing strategies. In turn, there are many methodological pitfalls in this literature, which prevent conclusive interpretation. The lack of robust intermediary obesity-related biomarkers is an additional unresolved challenge for prevention trials. Novel underpinning mechanisms (for example, local ectopic fat) and more accurate methods to measure these intermediaries are sought and explored as the most optimistic research strategies for the future. PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcomes vascular resection curative intent resection hilar cholangiocarcinoma multi institution study us extrahepatic biliary malignancy consortium background surgical resection cornerstone curative intent therapy patients hilar cholangiocarcinoma hc role vascular resection vr treatment hc western centres well defined methods utilizing data u extrahepatic biliary malignancy consortium patients grouped underwent resection hc based vr status vr portal vein resection pvr hepatic artery resection har perioperative long term survival outcomes analyzed results 1998 2015 201 patients underwent resection hc 31 15 underwent vr 19 patients 9 underwent pvr alone 12 patients 6 underwent har either n 2 without pvr n 10 patients selected vr tended younger higher stage disease rates postoperative complications 30 day mortality similar stratified vascular resection status multivariate analysis receipt pvr har significantly affect os rfs conclusion modern multi institutional cohort patients undergoing curative intent resection hc vr appears safe procedure highly selected subset although long term survival outcomes appear equivalent vr considered select patients based tumor patient characteristics pubmed","probabilities":0.9799733,"Title":"Outcomes after vascular resection during curative-intent resection for hilar cholangiocarcinoma: a multi-institution study from the US extrahepatic biliary malignancy consortium","Abstract":"BACKGROUND: Surgical resection is the cornerstone of curative-intent therapy for patients with hilar cholangiocarcinoma (HC). The role of vascular resection (VR) in the treatment of HC in western centres is not well defined. METHODS: Utilizing data from the U.S. Extrahepatic Biliary Malignancy Consortium, patients were grouped into those who underwent resection for HC based on VR status: no VR, portal vein resection (PVR), or hepatic artery resection (HAR). Perioperative and long-term survival outcomes were analyzed. RESULTS: Between 1998 and 2015, 201 patients underwent resection for HC, of which 31 (15%) underwent VR: 19 patients (9%) underwent PVR alone and 12 patients (6%) underwent HAR either with (n = 2) or without PVR (n = 10). Patients selected for VR tended to be younger with higher stage disease. Rates of postoperative complications and 30-day mortality were similar when stratified by vascular resection status. On multivariate analysis, receipt of PVR or HAR did not significantly affect OS or RFS. CONCLUSION: In a modern, multi-institutional cohort of patients undergoing curative-intent resection for HC, VR appears to be a safe procedure in a highly selected subset, although long-term survival outcomes appear equivalent. VR should be considered only in select patients based on tumor and patient characteristics.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes after vascular resection during curative-intent resection for hilar cholangiocarcinoma: a multi-institution study from the US extrahepatic biliary malignancy consortium BACKGROUND: Surgical resection is the cornerstone of curative-intent therapy for patients with hilar cholangiocarcinoma (HC). The role of vascular resection (VR) in the treatment of HC in western centres is not well defined. METHODS: Utilizing data from the U.S. Extrahepatic Biliary Malignancy Consortium, patients were grouped into those who underwent resection for HC based on VR status: no VR, portal vein resection (PVR), or hepatic artery resection (HAR). Perioperative and long-term survival outcomes were analyzed. RESULTS: Between 1998 and 2015, 201 patients underwent resection for HC, of which 31 (15%) underwent VR: 19 patients (9%) underwent PVR alone and 12 patients (6%) underwent HAR either with (n = 2) or without PVR (n = 10). Patients selected for VR tended to be younger with higher stage disease. Rates of postoperative complications and 30-day mortality were similar when stratified by vascular resection status. On multivariate analysis, receipt of PVR or HAR did not significantly affect OS or RFS. CONCLUSION: In a modern, multi-institutional cohort of patients undergoing curative-intent resection for HC, VR appears to be a safe procedure in a highly selected subset, although long-term survival outcomes appear equivalent. VR should be considered only in select patients based on tumor and patient characteristics. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gastrointestinal cancers mississippi objectives according 2007 us census bureau report mississippi poorest state united states ranked last among 50 states overall quality health objective study describe gastrointestinal gi cancers mississippi overall mississippi delta region particular methods age adjusted incidence rates gi cancers 2003 2007 compiled mississippi cancer registry centers disease control prevention national program cancer registries retrieved compared among 18 mississippi delta counties 64 non delta counties entire state mississippi united states colorectal cancer incidence rates national rankings correlated influencing factors race obesity diabetes mellitus education unemployment rate availability health insurance primary care physicians physical activity diet per capita income results compared united states whole mississippi higher rates colon rectal cancers lower overall rate gallbladder cancers whites african americans gi cancers liver intrahepatic bile duct gallbladder cancers lower age adjusted incidence rates mississippi delta region large difference african americans whites delta region whites residing delta counties higher incidence rates african americans cancers except liver intrahepatic bile duct cancers conclusions majority gi cancers higher incidence rates mississippi delta non delta counties entire state united states disparities observed regional ethnic basis call targeted prevention efforts eliminate disparities gi cancer incidence rates pubmed","probabilities":0.9799733,"Title":"Gastrointestinal cancers in Mississippi","Abstract":"OBJECTIVES: According to a 2007 US Census Bureau report, Mississippi is the poorest state in the United States and is ranked last among all 50 states for overall quality of health. The objective of the study was to describe gastrointestinal (GI) cancers in Mississippi overall and the Mississippi Delta region in particular. METHODS: The age-adjusted incidence rates for GI cancers for 2003-2007, compiled from the Mississippi Cancer Registry and the Centers for Disease Control and Prevention's National Program of Cancer Registries, were retrieved and compared among 18 Mississippi Delta counties, 64 non-Delta counties, the entire state of Mississippi, and the United States. Colorectal cancer incidence rates and national rankings were correlated with influencing factors of race, obesity, diabetes mellitus, education, unemployment rate, availability of health insurance and primary care physicians, physical activity, diet, and per capita income. RESULTS: Compared with the United States as a whole, Mississippi had higher rates of colon and rectal cancers and a lower overall rate of gallbladder cancers in both whites and African Americans. Of all GI cancers, only liver, intrahepatic bile duct, and gallbladder cancers had lower age-adjusted incidence rates in the Mississippi Delta region. There was a large difference between African Americans and whites in the Delta region. Whites residing in the Delta counties had higher incidence rates than African Americans of all cancers except liver and intrahepatic bile duct cancers. CONCLUSIONS: The majority of GI cancers had higher incidence rates in the Mississippi Delta than non-Delta counties and in the entire state than the United States. These disparities observed on a regional and ethnic basis call for targeted prevention efforts to eliminate disparities in GI cancer incidence rates.","Source":"PubMed","category":"HUMAN","training_data":"Gastrointestinal cancers in Mississippi OBJECTIVES: According to a 2007 US Census Bureau report, Mississippi is the poorest state in the United States and is ranked last among all 50 states for overall quality of health. The objective of the study was to describe gastrointestinal (GI) cancers in Mississippi overall and the Mississippi Delta region in particular. METHODS: The age-adjusted incidence rates for GI cancers for 2003-2007, compiled from the Mississippi Cancer Registry and the Centers for Disease Control and Prevention's National Program of Cancer Registries, were retrieved and compared among 18 Mississippi Delta counties, 64 non-Delta counties, the entire state of Mississippi, and the United States. Colorectal cancer incidence rates and national rankings were correlated with influencing factors of race, obesity, diabetes mellitus, education, unemployment rate, availability of health insurance and primary care physicians, physical activity, diet, and per capita income. RESULTS: Compared with the United States as a whole, Mississippi had higher rates of colon and rectal cancers and a lower overall rate of gallbladder cancers in both whites and African Americans. Of all GI cancers, only liver, intrahepatic bile duct, and gallbladder cancers had lower age-adjusted incidence rates in the Mississippi Delta region. There was a large difference between African Americans and whites in the Delta region. Whites residing in the Delta counties had higher incidence rates than African Americans of all cancers except liver and intrahepatic bile duct cancers. CONCLUSIONS: The majority of GI cancers had higher incidence rates in the Mississippi Delta than non-Delta counties and in the entire state than the United States. These disparities observed on a regional and ethnic basis call for targeted prevention efforts to eliminate disparities in GI cancer incidence rates. PubMed","prediction_labels":"HUMAN"},{"cleaned":"aso author reflections gallbladder cancer predictive risk score based pathological findings propensity score matched analysis past curative surgery offers good long term prognosis patients gallbladder carcinoma gbc 1 gbc subdivided two patterns identi cation one diagnosed symptoms abnormal laboratory ndings termed typical gbc whereas diagnosed incidentally cholecystectomy benign diseases designated incidental gbc icgbc previously ethun et al 2 demonstrated given subtle pathologic evaluations within stage gallbladder cancer predictive risk score gbrs better indicator prognosis icgbc tnm staging important assess usefulness gbrs gbc score provide index adjuvant chemotherapy aim study evaluate gbrs gbc using propensity score matched analysis present study found higher gbrs associated poor long term prognosis gbc even propensity score matched analysis gbrs signi cantly associated poor overall survival os recurrence free survival rfs 3 combined analysis gbrs preoperative cancer antigen ca 19 9 help guide patient selection additional treatment additional liver resection systemic perioperative chemotherapy creasy et al 4 reported locally advanced lymph node positive gbc patients undergo preoperative systemic chemotherapy patients show good response chemotherapy overcome dismal prognosis new predicting system combines gbrs preoperative ca19 9 used identify patients may bene adjuvant chemotherapy future study showed pathological data well preoperative ca19 9 elevation signi cantly associated dismal long term prognosis gbc even propensity matching analysis 3 however bene ts neoadjuvant adjuvant chemotherapy remain controversial new cancer therapies targeting blockade lymphangiogenic growth factors vascular endothelial growth factor vegf c vegf d entered clinical trials certain types tumors 5 studies urgently needed understand malignancy gbc best method combining surgical resection novel cancer therapeutics systemic chemotherapy improve long term prognosis preoperative ca19 9 gbrs useful selecting appropriate adjuvant chemotherapy regimens google scholar","probabilities":0.9799733,"Title":"Aso Author Reflections: Gallbladder Cancer Predictive Risk Score Based On Pathological Findings: A Propensity Score-Matched Analysis","Abstract":"PAST\nOnly curative surgery offers good long-term prognosis in patients with gallbladder carcinoma (GBC).1 GBC is subdivided into two patterns of identification: one is diagnosed from symptoms and abnormal laboratory findings (this is termed typical GBC), whereas the other is diagnosed incidentally after cholecystectomy for benign diseases (this is designated incidental GBC [ICGBC]). Previously, Ethun et al.2 demonstrated that given the subtle pathologic evaluations within each T stage, the gallbladder cancer predictive risk score (GBRS) is a better indicator of prognosis in ICGBC than TNM staging. It is important to assess the usefulness of the GBRS for GBC; this score could provide an index for adjuvant chemotherapy. The aim of this study was to evaluate GBRS in GBC using propensity score-matched analysis.\nPRESENT\nOur study found that a higher GBRS is associated with poor long-term prognosis in GBC. Even after propensity score-matched analysis, GBRS was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS).3 Combined analysis of GBRS and\npreoperative cancer antigen (CA) 19-9 can help guide patient selection for additional treatment, such as additional liver resection and systemic perioperative chemotherapy. Creasy et al.4 reported that locally advanced lymph node-positive GBC patients should undergo preoperative systemic chemotherapy because some patients show good response to chemotherapy. To overcome dismal prognosis, our new predicting system that combines GBRS and preoperative CA19-9 could be used to identify patients who may benefit from adjuvant chemotherapy.\nFUTURE\nOur study showed that pathological data, as well as preoperative CA19-9 elevation, were significantly associated with dismal long-term prognosis for GBC, even after propensity-matching analysis.3 However, the benefits of neoadjuvant and adjuvant chemotherapy remain controversial. New cancer therapies targeting the blockade of lymphangiogenic growth factors (vascular endothelial growth factor [VEGF]-C, VEGF-D) have entered clinical trials for certain types of tumors.5 Further studies are urgently needed to understand the malignancy of GBC and the best method for combining surgical resection, novel cancer therapeutics, and systemic chemotherapy to improve long-term prognosis. Preoperative CA19-9 and GBRS could be useful for selecting appropriate adjuvant chemotherapy regimens.","Source":"Google Scholar","category":"HUMAN","training_data":"Aso Author Reflections: Gallbladder Cancer Predictive Risk Score Based On Pathological Findings: A Propensity Score-Matched Analysis PAST\nOnly curative surgery offers good long-term prognosis in patients with gallbladder carcinoma (GBC).1 GBC is subdivided into two patterns of identification: one is diagnosed from symptoms and abnormal laboratory findings (this is termed typical GBC), whereas the other is diagnosed incidentally after cholecystectomy for benign diseases (this is designated incidental GBC [ICGBC]). Previously, Ethun et al.2 demonstrated that given the subtle pathologic evaluations within each T stage, the gallbladder cancer predictive risk score (GBRS) is a better indicator of prognosis in ICGBC than TNM staging. It is important to assess the usefulness of the GBRS for GBC; this score could provide an index for adjuvant chemotherapy. The aim of this study was to evaluate GBRS in GBC using propensity score-matched analysis.\nPRESENT\nOur study found that a higher GBRS is associated with poor long-term prognosis in GBC. Even after propensity score-matched analysis, GBRS was significantly associated with poor overall survival (OS) and recurrence-free survival (RFS).3 Combined analysis of GBRS and\npreoperative cancer antigen (CA) 19-9 can help guide patient selection for additional treatment, such as additional liver resection and systemic perioperative chemotherapy. Creasy et al.4 reported that locally advanced lymph node-positive GBC patients should undergo preoperative systemic chemotherapy because some patients show good response to chemotherapy. To overcome dismal prognosis, our new predicting system that combines GBRS and preoperative CA19-9 could be used to identify patients who may benefit from adjuvant chemotherapy.\nFUTURE\nOur study showed that pathological data, as well as preoperative CA19-9 elevation, were significantly associated with dismal long-term prognosis for GBC, even after propensity-matching analysis.3 However, the benefits of neoadjuvant and adjuvant chemotherapy remain controversial. New cancer therapies targeting the blockade of lymphangiogenic growth factors (vascular endothelial growth factor [VEGF]-C, VEGF-D) have entered clinical trials for certain types of tumors.5 Further studies are urgently needed to understand the malignancy of GBC and the best method for combining surgical resection, novel cancer therapeutics, and systemic chemotherapy to improve long-term prognosis. Preoperative CA19-9 and GBRS could be useful for selecting appropriate adjuvant chemotherapy regimens. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cytologic predictors malignancy bile duct brushings multi reviewer analysis 60 cases diagnosing malignancy bile duct brushings highly challenging seven reviewers variable backgrounds levels participation bile duct brushing sign blindly reviewed 60 specimens 30 malignant histologic confirmation 30 benign 15 stented resection 18 months uneventful follow testing utility 14 malignant characteristics eleven characteristics statistically significantly associated malignancy including 3 dimensional clusters 63 malignant vs 3 benign odds ratio 50 p 0 0003 pleomorphism 62 vs 3 odds ratio 48 p 0 0004 2 cell population 60 vs 3 odds ratio 44 p 0 0005 chromatin pattern hypo hyperchromasia changes 70 vs 7 odds ratio 33 p 0 0001 high nuclear cytoplasmic ratio 48 vs 3 odds ratio 27 p 0 0023 cytoplasmic vacuoles 43 vs 3 odds ratio 22 p 0 0042 nuclear irregularity 70 vs 10 odds ratio 21 p 0 0001 cellular discohesion 38 vs 3 odds ratio 18 p 0 0082 hypercellularity 23 vs 0 nuclear molding 20 vs 0 prominent nucleoli 21 vs 0 necrosis infiltrating inflammation helpful identifying malignancy neutrophil cannibalism noted 43 malignant 21 30 70 malignant brushings 3 malignant characteristics 23 77 benign brushings none 20 brushings 4 characteristics 1 5 proved benign showed detachment atypia close malignant mimicker brushings identification 3 characteristics maximized combined sensitivity 70 specificity 97 accuracy 83 sensitivity dropped number characteristics increased identification 3 11 characteristics 3 dimensional clusters pleomorphism high nuclear cytoplasmic ratio nuclear irregularity hypercellularity discohesion chromatin changes vacuoles prominent nucleoli molding 2 cell population improves pathologists overall performance greatly stn","probabilities":0.9467213,"Title":"Cytologic Predictors Of Malignancy In Bile Duct Brushings: A Multi-Reviewer Analysis Of 60 Cases","Abstract":"Diagnosing malignancy in bile duct brushings is highly challenging. Seven reviewers of variable backgrounds and levels of participation in bile duct brushing sign out blindly reviewed 60 specimens (30 malignant with histologic confirmation and 30 benign (15 stented) with resection or ≥18 months of uneventful follow-up), testing the utility of 14 malignant characteristics. Eleven characteristics were statistically significantly associated with malignancy including 3-dimensional clusters (63% in malignant vs 3% in benign, odds ratio 50, P=0.0003), pleomorphism (62 vs 3, odds ratio 48, P=0.0004), 2-cell population (60% vs 3, odds ratio 44, P=0.0005), chromatin pattern (hypo/hyperchromasia) changes (70% vs 7%, odds ratio 33, P<0.0001), high nuclear-to-cytoplasmic ratio (48 vs 3%, odds ratio 27, P=0.0023), cytoplasmic vacuoles (43 vs 3%, odds ratio 22, P=0.0042), nuclear irregularity (70 vs 10%, odds ratio 21, P<0.0001), cellular discohesion (38 vs 3%, odds ratio 18, P=0.0082), hypercellularity (23% vs 0), nuclear molding (20% vs 0) and prominent nucleoli (21% vs 0). Necrosis and infiltrating inflammation were not helpful in identifying malignancy ('neutrophil cannibalism' was noted in 43% malignant); 21/30 (70%) malignant brushings had ≥3 malignant characteristics, while 23 (77%) benign brushings had none. Of 20 brushings with ≥4 characteristics, 1(5%) proved benign and showed detachment atypia, a close malignant mimicker in brushings. Identification of 3 characteristics maximized the combined sensitivity (70%), specificity (97%) and accuracy (83%), but sensitivity dropped as number of characteristics increased. Identification of 3/11 characteristics (3-dimensional clusters, pleomorphism, high nuclear-to-cytoplasmic ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2-cell population) improves pathologists' overall performance greatly.","Source":"STN","category":"ANIMAL","training_data":"Cytologic Predictors Of Malignancy In Bile Duct Brushings: A Multi-Reviewer Analysis Of 60 Cases Diagnosing malignancy in bile duct brushings is highly challenging. Seven reviewers of variable backgrounds and levels of participation in bile duct brushing sign out blindly reviewed 60 specimens (30 malignant with histologic confirmation and 30 benign (15 stented) with resection or ≥18 months of uneventful follow-up), testing the utility of 14 malignant characteristics. Eleven characteristics were statistically significantly associated with malignancy including 3-dimensional clusters (63% in malignant vs 3% in benign, odds ratio 50, P=0.0003), pleomorphism (62 vs 3, odds ratio 48, P=0.0004), 2-cell population (60% vs 3, odds ratio 44, P=0.0005), chromatin pattern (hypo/hyperchromasia) changes (70% vs 7%, odds ratio 33, P<0.0001), high nuclear-to-cytoplasmic ratio (48 vs 3%, odds ratio 27, P=0.0023), cytoplasmic vacuoles (43 vs 3%, odds ratio 22, P=0.0042), nuclear irregularity (70 vs 10%, odds ratio 21, P<0.0001), cellular discohesion (38 vs 3%, odds ratio 18, P=0.0082), hypercellularity (23% vs 0), nuclear molding (20% vs 0) and prominent nucleoli (21% vs 0). Necrosis and infiltrating inflammation were not helpful in identifying malignancy ('neutrophil cannibalism' was noted in 43% malignant); 21/30 (70%) malignant brushings had ≥3 malignant characteristics, while 23 (77%) benign brushings had none. Of 20 brushings with ≥4 characteristics, 1(5%) proved benign and showed detachment atypia, a close malignant mimicker in brushings. Identification of 3 characteristics maximized the combined sensitivity (70%), specificity (97%) and accuracy (83%), but sensitivity dropped as number of characteristics increased. Identification of 3/11 characteristics (3-dimensional clusters, pleomorphism, high nuclear-to-cytoplasmic ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2-cell population) improves pathologists' overall performance greatly. STN","prediction_labels":"ANIMAL"},{"cleaned":"effects statin aspirin metformin use recurrence free overall survival patients biliary tract cancer background aims impact statins aspirin metformin use recurrence free rfs overall survival os patients biliary tract cancer btc evaluated methodology baseline demographics comorbidity use statins aspirin metformin diagnosis evaluated patients btc january 1987 july 2013 results median age diagnosis 65 7 years performance status 2 795 patients male 461 50 5 among 913 patients 151 16 5 reported statin use diagnosis 146 16 aspirin use 81 9 metformin use charlson comorbidity index score significantly associated rfs os stage prognostic multivariable analysis rfs os p 0 001 age performance status 2 site also prognostic os p 0 05 p 0 001 p 0 05 respectively recurrence free os among statin users nonusers similar rfs hazard ratio hr 1 11 95 confidence interval ci 0 78 1 58 p 0 57 os hr0 98 95 ci 0 77 1 24 p 0 86 among aspirin users nonusers rfs hr0 83 95 ci 0 57 1 23 p 0 35 os hr1 07 95 ci 0 85 1 34 p 0 58 among metformin users non users rfs hr0 75 95 ci 0 43 1 30 p 0 30 os hr0 96 95 ci 0 69 1 33 p 0 79 conclusion large retrospective cohort btc patients comorbidity statin aspirin metformin use significant effects rfs os pubmed","probabilities":0.9799733,"Title":"Effects of Statin, Aspirin or Metformin Use on Recurrence-Free and Overall Survival in Patients with Biliary Tract Cancer","Abstract":"BACKGROUND/AIMS: The impact of statins, aspirin and metformin use on recurrence-free (RFS) and overall survival (OS) of patients with biliary tract cancer (BTC) has not been evaluated. METHODOLOGY: Baseline demographics/comorbidity and use of statins, aspirin or metformin at diagnosis were evaluated in patients with BTC from January/1987-July/2013. RESULTS: Median age at diagnosis; 65.7 years, performance status < 2; 795 patients, male; 461 (50.5%). Among 913 patients; 151 (16.5%) reported statin use at diagnosis, 146 (16%) aspirin use, and 81 (9%) metformin use. Charlson Comorbidity index score was not significantly associated with RFS or OS. Stage was prognostic on multivariable analysis for RFS and OS (both P ≤ 0.001) and age, performance status ≥ 2 and site were also prognostic for OS (P < 0.05, P < 0.001, and P < 0.05 respectively). Recurrence-free and OS among statin-users and nonusers was similar (RFS Hazard Ratio [HR]1.11, 95% confidence interval [CI] 0.78 - 1.58, P = 0.57), (OS HR0.98, 95% CI 0.77-1.24, P = 0.86), and among aspirin-users and nonusers (RFS HR0.83, 95% CI 0.57-1.23, P = 0.35), (OS HR1.07, 95% CI 0.85 - 1.34, P = 0.58), and among metformin-users and non-users (RFS HR0.75, 95% CI 0.43-1.30, P = 0.30), (OS HR0.96, 95% CI 0.69-1.33, P = 0.79). CONCLUSION: In this large retrospective cohort of BTC patients, comorbidity, statin, aspirin or metformin use did not have significant effects on RFS or OS.","Source":"PubMed","category":"HUMAN","training_data":"Effects of Statin, Aspirin or Metformin Use on Recurrence-Free and Overall Survival in Patients with Biliary Tract Cancer BACKGROUND/AIMS: The impact of statins, aspirin and metformin use on recurrence-free (RFS) and overall survival (OS) of patients with biliary tract cancer (BTC) has not been evaluated. METHODOLOGY: Baseline demographics/comorbidity and use of statins, aspirin or metformin at diagnosis were evaluated in patients with BTC from January/1987-July/2013. RESULTS: Median age at diagnosis; 65.7 years, performance status < 2; 795 patients, male; 461 (50.5%). Among 913 patients; 151 (16.5%) reported statin use at diagnosis, 146 (16%) aspirin use, and 81 (9%) metformin use. Charlson Comorbidity index score was not significantly associated with RFS or OS. Stage was prognostic on multivariable analysis for RFS and OS (both P ≤ 0.001) and age, performance status ≥ 2 and site were also prognostic for OS (P < 0.05, P < 0.001, and P < 0.05 respectively). Recurrence-free and OS among statin-users and nonusers was similar (RFS Hazard Ratio [HR]1.11, 95% confidence interval [CI] 0.78 - 1.58, P = 0.57), (OS HR0.98, 95% CI 0.77-1.24, P = 0.86), and among aspirin-users and nonusers (RFS HR0.83, 95% CI 0.57-1.23, P = 0.35), (OS HR1.07, 95% CI 0.85 - 1.34, P = 0.58), and among metformin-users and non-users (RFS HR0.75, 95% CI 0.43-1.30, P = 0.30), (OS HR0.96, 95% CI 0.69-1.33, P = 0.79). CONCLUSION: In this large retrospective cohort of BTC patients, comorbidity, statin, aspirin or metformin use did not have significant effects on RFS or OS. PubMed","prediction_labels":"HUMAN"},{"cleaned":"glasgow prognostic score predicts outcome surgical resection gallbladder cancer background systemic inflammation evidenced glasgow prognostic score gps predicts cancer specific survival various types cancer aim study evaluate significance gps therapeutic outcome surgical resection gallbladder cancer methods subjects 51 patients underwent surgical resection gallbladder cancer assessment systemic inflammatory response using gps patients classified three groups patients normal albumin 3 5 g dl normal c reactive protein crp 1 0 mg dl gps 0 n 38 low albumin 3 5 g dl elevated crp 1 0 mg dl gps 1 n 8 low albumin 3 5 g dl elevated crp 1 0 mg dl gps 2 n 5 retrospectively investigated relation patient characteristics including gps disease free well overall survival results disease free survival advanced tumor stage based pathology p 0 006 positive lymph node metastasis p 0 001 gps 1 2 p 0 006 independent predictors cancer recurrence multivariate analysis overall survival positive lymph node metastasis p 0 002 gps 1 2 p 0 032 independent predictors poor patient outcome multivariate analyses conclusion gps patients gallbladder cancer independent prognostic predictor surgical resection pubmed","probabilities":0.9799733,"Title":"Glasgow prognostic score predicts outcome after surgical resection of gallbladder cancer","Abstract":"BACKGROUND: Systemic inflammation as evidenced by the Glasgow prognostic score (GPS) predicts cancer-specific survival in various types of cancer. The aim of this study was to evaluate the significance of GPS in therapeutic outcome after surgical resection of gallbladder cancer. METHODS: The subjects were 51 patients who underwent surgical resection for gallbladder cancer. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: patients with normal albumin (≥3.5 g/dl) and normal C-reactive protein (CRP) (≤1.0 mg/dl) as GPS 0 (n = 38), those with low albumin (<3.5 g/dl) or elevated CRP (>1.0 mg/dl) as GPS 1 (n = 8), and those with low albumin (<3.5 g/dl) and elevated CRP (>1.0 mg/dl) as GPS 2 (n = 5). We retrospectively investigated the relation between patient characteristics including GPS, and disease-free as well as overall survival. RESULTS: In disease-free survival, advanced tumor stage based on pathology (p = 0.006), positive lymph node metastasis (p = 0.001), and GPS 1 or 2 (p = 0.006) were independent predictors of cancer recurrence in multivariate analysis. In overall survival, positive lymph node metastasis (p = 0.002) and GPS 1 or 2 (p = 0.032) were independent predictors of poor patient outcome in multivariate analyses. CONCLUSION: The GPS in patients with gallbladder cancer is an independent prognostic predictor after surgical resection.","Source":"PubMed","category":"HUMAN","training_data":"Glasgow prognostic score predicts outcome after surgical resection of gallbladder cancer BACKGROUND: Systemic inflammation as evidenced by the Glasgow prognostic score (GPS) predicts cancer-specific survival in various types of cancer. The aim of this study was to evaluate the significance of GPS in therapeutic outcome after surgical resection of gallbladder cancer. METHODS: The subjects were 51 patients who underwent surgical resection for gallbladder cancer. For the assessment of systemic inflammatory response using the GPS, patients were classified into three groups: patients with normal albumin (≥3.5 g/dl) and normal C-reactive protein (CRP) (≤1.0 mg/dl) as GPS 0 (n = 38), those with low albumin (<3.5 g/dl) or elevated CRP (>1.0 mg/dl) as GPS 1 (n = 8), and those with low albumin (<3.5 g/dl) and elevated CRP (>1.0 mg/dl) as GPS 2 (n = 5). We retrospectively investigated the relation between patient characteristics including GPS, and disease-free as well as overall survival. RESULTS: In disease-free survival, advanced tumor stage based on pathology (p = 0.006), positive lymph node metastasis (p = 0.001), and GPS 1 or 2 (p = 0.006) were independent predictors of cancer recurrence in multivariate analysis. In overall survival, positive lymph node metastasis (p = 0.002) and GPS 1 or 2 (p = 0.032) were independent predictors of poor patient outcome in multivariate analyses. CONCLUSION: The GPS in patients with gallbladder cancer is an independent prognostic predictor after surgical resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic impact number involved lymph nodes distal cholangiocarcinoma introduction nodal status fully addressed distal cholangiocarcinoma previous studies involved limited number patients 100 conducted multi institutional study verify prognostic impact number involved lymph nodes distal tumor method total 188 patients distal cholangiocarcinoma middle tumor n 74 lower tumor n 114 underwent surgical resection 2001 2010 reviewed pancreatoduodectomy bile duct resection performed 171 17 patients respectively nodal metastasis histologically de ned according ajcc cancer staging manual number lymph nodes examined histologically 17 median range 1 51 results nodal metastasis found 90 48 patients number involved node ranged 1 13 single metastasis common n 38 followed two n 22 three n 15 survival rate 90 patients nodal metastasis 28 3 years 24 5 years 98 patients without nodal metastasis 71 63 respectively p 0 001 survival rates patients groups 1 2 3 involved nodes largely overlapped patients strati ed according number involved nodes 1 3 vs 4 former group showed better survival latter 3 year survival rates 34 vs 0 respectively p 0 001 worse survival rate node negative group p 0 001 cox regression analysis identi ed independent predictors number involved node p 0 001 pancreatic invasion p 0 009 major vascular invasion p 0 012 conclusions increased number involved nodes correlated poor survival distal cholangiocarcinoma patients 4 involved nodes categorized independent stage 3 less involved nodes google scholar","probabilities":0.9799733,"Title":"Prognostic Impact Of The Number Of Involved Lymph Nodes In Distal Cholangiocarcinoma","Abstract":"Introduction: The nodal status has not been fully addressed in distal cholangiocarcinoma, because previous studies have involved a limited number of patients (<100). We conducted a multi-institutional study to verify the prognostic impact of the number of involved lymph nodes in distal tumor. Method: A total of 188 patients with distal cholangiocarcinoma (middle tumor, n = 74; lower tumor, n = 114) who underwent surgical resection between 2001 and 2010 was the reviewed. Pancreatoduodectomy and bile duct resection were performed in 171 and 17 patients, respectively. The nodal metastasis was histologically defined according to the AJCC cancer staging manual. The number of lymph nodes examined histologically was 17 in median (range, 1–51). Results: Nodal metastasis was found in 90 (48%) patients. The number of involved node ranged from 1 to 13; single metastasis was the most common (n = 38), followed by two (n = 22), and three (n = 15). Survival rate for the 90 patients with nodal metastasis was 28% at 3-years and 24% at 5-years; that for the 98 patients without nodal metastasis was 71% and 63%, respectively (p < 0.001). Because the survival rates of the patients groups with 1, 2, or 3 involved nodes largely overlapped, the patients were stratified according to the number of involved nodes (1–3 vs. 4 or more). The former group showed a better survival than the latter with 3-year survival rates of 34% vs. 0, respectively (p < 0.001), and a worse survival rate than node-negative group (p < 0.001). Cox regression analysis identified there independent predictors: the number of involved node (p < 0.001), pancreatic invasion (p = 0.009), and major vascular invasion (p = 0.012). Conclusions: The increased number of involved nodes correlated with poor survival in distal cholangiocarcinoma. The patients with 4 or more involved nodes should be categorized as an independent stage from those with 3 or less involved nodes.","Source":"Google Scholar","category":"HUMAN","training_data":"Prognostic Impact Of The Number Of Involved Lymph Nodes In Distal Cholangiocarcinoma Introduction: The nodal status has not been fully addressed in distal cholangiocarcinoma, because previous studies have involved a limited number of patients (<100). We conducted a multi-institutional study to verify the prognostic impact of the number of involved lymph nodes in distal tumor. Method: A total of 188 patients with distal cholangiocarcinoma (middle tumor, n = 74; lower tumor, n = 114) who underwent surgical resection between 2001 and 2010 was the reviewed. Pancreatoduodectomy and bile duct resection were performed in 171 and 17 patients, respectively. The nodal metastasis was histologically defined according to the AJCC cancer staging manual. The number of lymph nodes examined histologically was 17 in median (range, 1–51). Results: Nodal metastasis was found in 90 (48%) patients. The number of involved node ranged from 1 to 13; single metastasis was the most common (n = 38), followed by two (n = 22), and three (n = 15). Survival rate for the 90 patients with nodal metastasis was 28% at 3-years and 24% at 5-years; that for the 98 patients without nodal metastasis was 71% and 63%, respectively (p < 0.001). Because the survival rates of the patients groups with 1, 2, or 3 involved nodes largely overlapped, the patients were stratified according to the number of involved nodes (1–3 vs. 4 or more). The former group showed a better survival than the latter with 3-year survival rates of 34% vs. 0, respectively (p < 0.001), and a worse survival rate than node-negative group (p < 0.001). Cox regression analysis identified there independent predictors: the number of involved node (p < 0.001), pancreatic invasion (p = 0.009), and major vascular invasion (p = 0.012). Conclusions: The increased number of involved nodes correlated with poor survival in distal cholangiocarcinoma. The patients with 4 or more involved nodes should be categorized as an independent stage from those with 3 or less involved nodes. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cell lineage tracing reveals biliary origin intrahepatic cholangiocarcinoma intrahepatic cholangiocarcinoma treatment refractory malignancy high mortality increasing incidence worldwide recent studies observed activation notch akt signaling within mature hepatocytes able induce formation tumors displaying biliary lineage markers thereby raising suggestion hepatocytes rather cholangiocytes hepatic progenitor cells represent cell origin tumor use cholangiocyte lineage tracing system target p53 loss biliary epithelia observe appearance labeled biliary lineage tumors response chronic injury consequent upregulation native functional notch signaling observed occur spontaneously within cholangiocytes hepatocytes model well human intrahepatic cholangiocarcinoma data prove context chronic inflammation p53 loss frequent occurrences human disease biliary epithelia target transformation origin intrahepatic cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Cell Lineage Tracing Reveals A Biliary Origin Of Intrahepatic Cholangiocarcinoma","Abstract":"Intrahepatic cholangiocarcinoma is a treatment refractory malignancy with a high mortality and an increasing incidence worldwide. Recent studies have observed that activation of Notch and AKT signaling within mature hepatocytes is able to induce the formation of tumors displaying biliary lineage markers, thereby raising the suggestion that it is hepatocytes, rather than cholangiocytes or hepatic progenitor cells that represent the cell of origin of this tumor. Here, we use a cholangiocyte-lineage tracing system to target p53 loss to biliary epithelia and observe the appearance of labeled biliary lineage tumors in response to chronic injury. Consequent to this, upregulation of native functional Notch signaling is observed to occur spontaneously within cholangiocytes and hepatocytes in this model as well as in human intrahepatic cholangiocarcinoma. These data prove that in the context of chronic inflammation and p53 loss, frequent occurrences in human disease, biliary epithelia are a target of transformation and an origin of intrahepatic cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Cell Lineage Tracing Reveals A Biliary Origin Of Intrahepatic Cholangiocarcinoma Intrahepatic cholangiocarcinoma is a treatment refractory malignancy with a high mortality and an increasing incidence worldwide. Recent studies have observed that activation of Notch and AKT signaling within mature hepatocytes is able to induce the formation of tumors displaying biliary lineage markers, thereby raising the suggestion that it is hepatocytes, rather than cholangiocytes or hepatic progenitor cells that represent the cell of origin of this tumor. Here, we use a cholangiocyte-lineage tracing system to target p53 loss to biliary epithelia and observe the appearance of labeled biliary lineage tumors in response to chronic injury. Consequent to this, upregulation of native functional Notch signaling is observed to occur spontaneously within cholangiocytes and hepatocytes in this model as well as in human intrahepatic cholangiocarcinoma. These data prove that in the context of chronic inflammation and p53 loss, frequent occurrences in human disease, biliary epithelia are a target of transformation and an origin of intrahepatic cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"cholangiocarcinoma pan pacific perspective nan pubmed","probabilities":0.9799733,"Title":"Cholangiocarcinoma: a pan-Pacific perspective","Abstract":"NaN","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma: a pan-Pacific perspective nan PubMed","prediction_labels":"HUMAN"},{"cleaned":"l1 cell adhesion molecule novel independent poor prognostic factor gallbladder carcinoma gallbladder carcinoma lethal malignancy hard cure current treatment thus identification molecular prognostic markers predict gallbladder carcinoma therapeutic targets urgently needed recent studies demonstrated l1 cell adhesion molecule associated prognosis variable malignancy investigated l1 cell adhesion molecule expression gallbladder carcinoma prognostic significance study examined l1 cell adhesion molecule expression tumor specimens 69 patients gallbladder carcinoma immunohistochemistry analyzed correlation l1 cell adhesion molecule expression clinicopathologic factors survival l1 cell adhesion molecule expressed normal epithelium gallbladder 63 8 gallbladder carcinomas remarkably invasive front tumors addition l1 cell adhesion molecule expression significantly associated high histologic grade advanced pathologic stage clinical stage positive venous lymphatic invasion multivariate analyses showed l1 cell adhesion molecule expression hazard ratio 3 503 p 028 clinical stage hazard ratio 3 091 p 042 independent risk factor disease free survival l1 cell adhesion molecule expression gallbladder carcinoma significantly correlated tumor progression unfavorable clinicopathologic features l1 cell adhesion molecule expression independent poor prognostic factor disease free survival patients gallbladder carcinoma taken together findings suggest l1 cell adhesion molecule expression used novel prognostic factor patient survival might potential therapeutic target gallbladder carcinomas pubmed","probabilities":0.962963,"Title":"L1 cell adhesion molecule as a novel independent poor prognostic factor in gallbladder carcinoma","Abstract":"Gallbladder carcinoma is a lethal malignancy and is hard to cure by current treatment. Thus, identification of molecular prognostic markers to predict gallbladder carcinoma as therapeutic targets is urgently needed. Recent studies have demonstrated that L1 cell adhesion molecule is associated with the prognosis of variable malignancy. Here, we investigated L1 cell adhesion molecule expression in gallbladder carcinoma and its prognostic significance. In this study, we examined L1 cell adhesion molecule expression in tumor specimens from 69 patients with gallbladder carcinoma by immunohistochemistry and analyzed the correlation between L1 cell adhesion molecule expression and clinicopathologic factors or survival. L1 cell adhesion molecule was not expressed in the normal epithelium of the gallbladder but in 63.8% of gallbladder carcinomas, remarkably at the invasive front of the tumors. In addition, L1 cell adhesion molecule expression was significantly associated with high histologic grade, advanced pathologic T stage and clinical stage, and positive venous/lymphatic invasion. Multivariate analyses showed that L1 cell adhesion molecule expression (hazard ratio, 3.503; P = .028) and clinical stage (hazard ratio, 3.091; P = .042) were independent risk factor for disease-free survival. L1 cell adhesion molecule expression in gallbladder carcinoma was significantly correlated with tumor progression and unfavorable clinicopathologic features. L1 cell adhesion molecule expression was an independent poor prognostic factor for disease-free survival in patients with gallbladder carcinoma. Taken together, our findings suggest that L1 cell adhesion molecule expression could be used as a novel prognostic factor for patient survival and might be a potential therapeutic target in gallbladder carcinomas.","Source":"PubMed","category":"HUMAN","training_data":"L1 cell adhesion molecule as a novel independent poor prognostic factor in gallbladder carcinoma Gallbladder carcinoma is a lethal malignancy and is hard to cure by current treatment. Thus, identification of molecular prognostic markers to predict gallbladder carcinoma as therapeutic targets is urgently needed. Recent studies have demonstrated that L1 cell adhesion molecule is associated with the prognosis of variable malignancy. Here, we investigated L1 cell adhesion molecule expression in gallbladder carcinoma and its prognostic significance. In this study, we examined L1 cell adhesion molecule expression in tumor specimens from 69 patients with gallbladder carcinoma by immunohistochemistry and analyzed the correlation between L1 cell adhesion molecule expression and clinicopathologic factors or survival. L1 cell adhesion molecule was not expressed in the normal epithelium of the gallbladder but in 63.8% of gallbladder carcinomas, remarkably at the invasive front of the tumors. In addition, L1 cell adhesion molecule expression was significantly associated with high histologic grade, advanced pathologic T stage and clinical stage, and positive venous/lymphatic invasion. Multivariate analyses showed that L1 cell adhesion molecule expression (hazard ratio, 3.503; P = .028) and clinical stage (hazard ratio, 3.091; P = .042) were independent risk factor for disease-free survival. L1 cell adhesion molecule expression in gallbladder carcinoma was significantly correlated with tumor progression and unfavorable clinicopathologic features. L1 cell adhesion molecule expression was an independent poor prognostic factor for disease-free survival in patients with gallbladder carcinoma. Taken together, our findings suggest that L1 cell adhesion molecule expression could be used as a novel prognostic factor for patient survival and might be a potential therapeutic target in gallbladder carcinomas. PubMed","prediction_labels":"HUMAN"},{"cleaned":"percutaneous hepatic perfusion chemosaturation melphalan patients intrahepatic cholangiocarcinoma european multicentre study safety short term effects survival objectives cholangiocarcinoma second common primary liver tumour poor overall prognosis percutaneous hepatic perfusion php directed therapy primary secondary liver malignancies efficacy safety shown different entities purpose study prove safety efficacy php patients unresectable intrahepatic cholangiocarcinoma icca patients methods retrospectively reviewed data 15 patients unresectable icca treated php nine different hospitals throughout europe overall response rates orr assessed according response evaluation criteria solid tumours recist1 1 overall survival os progression free survival pfs hepatic pfs hpfs analysed using kaplan meier estimation adverse events aes toxicity evaluated results fifteen patients treated 26 phps orr 20 disease control achieved 53 first php median os 26 9 months initial diagnosis 7 6 months first php median pfs hpfs 122 131 days respectively patients liver disease significantly longer median os compared patients locoregional lymph node metastases 12 9 vs 4 8 months respectively p 0 01 haematological toxicity common manageable aes grade 3 4 occurred procedures discussion php standardised safe procedure provides promising response rates survival data patients icca especially non metastatic disease key points percutaneous hepatic perfusion php offers additional locoregional therapy strategy treatment unresectable primary secondary intrahepatic malignancies php standardised safe procedure provides promising response rates survival data patients intrahepatic cholangiocarcinoma icca especially non metastatic disease side effects seem tolerable comparable systemic local treatment strategies pubmed","probabilities":0.9799733,"Title":"Percutaneous hepatic perfusion (chemosaturation) with melphalan in patients with intrahepatic cholangiocarcinoma: European multicentre study on safety, short-term effects and survival","Abstract":"OBJECTIVES: Cholangiocarcinoma is the second most common primary liver tumour with a poor overall prognosis. Percutaneous hepatic perfusion (PHP) is a directed therapy for primary and secondary liver malignancies, and its efficacy and safety have been shown in different entities. The purpose of this study was to prove the safety and efficacy of PHP in patients with unresectable intrahepatic cholangiocarcinoma (iCCA). PATIENTS AND METHODS: We retrospectively reviewed data from 15 patients with unresectable iCCA treated with PHP in nine different hospitals throughout Europe. Overall response rates (ORR) were assessed according to response evaluation criteria in solid tumours (RECIST1.1). Overall survival (OS), progression-free survival (PFS) and hepatic PFS (hPFS) were analysed using the Kaplan-Meier estimation. Adverse events (AEs) and toxicity were evaluated. RESULTS: Fifteen patients were treated with 26 PHPs. ORR was 20%, disease control was achieved in 53% after the first PHP. Median OS was 26.9 months from initial diagnosis and 7.6 months from first PHP. Median PFS and hPFS were 122 and 131 days, respectively. Patients with liver-only disease had a significantly longer median OS compared to patients with locoregional lymph node metastases (12.9 vs. 4.8 months, respectively; p < 0.01). Haematological toxicity was common, but manageable. No AEs of grade 3 or 4 occurred during the procedures. DISCUSSION: PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with iCCA, especially in non-metastatic disease. KEY POINTS: • Percutaneous hepatic perfusion (PHP) offers an additional locoregional therapy strategy for the treatment of unresectable primary or secondary intrahepatic malignancies. • PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with intrahepatic cholangiocarcinoma (iCCA), especially in non-metastatic disease. • Side effects seem to be tolerable and comparable to other systemic or local treatment strategies.","Source":"PubMed","category":"HUMAN","training_data":"Percutaneous hepatic perfusion (chemosaturation) with melphalan in patients with intrahepatic cholangiocarcinoma: European multicentre study on safety, short-term effects and survival OBJECTIVES: Cholangiocarcinoma is the second most common primary liver tumour with a poor overall prognosis. Percutaneous hepatic perfusion (PHP) is a directed therapy for primary and secondary liver malignancies, and its efficacy and safety have been shown in different entities. The purpose of this study was to prove the safety and efficacy of PHP in patients with unresectable intrahepatic cholangiocarcinoma (iCCA). PATIENTS AND METHODS: We retrospectively reviewed data from 15 patients with unresectable iCCA treated with PHP in nine different hospitals throughout Europe. Overall response rates (ORR) were assessed according to response evaluation criteria in solid tumours (RECIST1.1). Overall survival (OS), progression-free survival (PFS) and hepatic PFS (hPFS) were analysed using the Kaplan-Meier estimation. Adverse events (AEs) and toxicity were evaluated. RESULTS: Fifteen patients were treated with 26 PHPs. ORR was 20%, disease control was achieved in 53% after the first PHP. Median OS was 26.9 months from initial diagnosis and 7.6 months from first PHP. Median PFS and hPFS were 122 and 131 days, respectively. Patients with liver-only disease had a significantly longer median OS compared to patients with locoregional lymph node metastases (12.9 vs. 4.8 months, respectively; p < 0.01). Haematological toxicity was common, but manageable. No AEs of grade 3 or 4 occurred during the procedures. DISCUSSION: PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with iCCA, especially in non-metastatic disease. KEY POINTS: • Percutaneous hepatic perfusion (PHP) offers an additional locoregional therapy strategy for the treatment of unresectable primary or secondary intrahepatic malignancies. • PHP is a standardised and safe procedure that provides promising response rates and survival data in patients with intrahepatic cholangiocarcinoma (iCCA), especially in non-metastatic disease. • Side effects seem to be tolerable and comparable to other systemic or local treatment strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"incidence mortality trends cholangiocarcinoma asian patients different ethnicities background cholangiocarcinoma common biliary cancer second common primary cancer liver estimated cholangiocarcinoma responsible 13 overall cancer related mortality worldwide study examined incidence mortality temporal trends cholangiocarcinoma since year 2000 methods used seer 18 database study cholangiocarcinoma cases us 2000 2015 incidence mortality rates cholangiocarcinoma calculated race expressed 1 000 000 person years annual percent change apc calculated using joinpoint regression software results reviewed 2 191 patients cholangiocarcinoma patients caucasians 1 800 followed blacks 193 asians 182 american indians 16 incidence rates 1 643 1 431 1 451 1 199 per 100 000 person years respectively incidence rates cholangiocarcinoma significantly change study period among caucasians apc 1 345 p value 0 06 blacks apc 1 085 p value 0 22 asians apc 0 48 p value 0 76 mortality due cholangiocarcinoma 1 391 1 203 1 194 1 029 per 100 000 person years caucasians blacks asians american indians respectively mortality rates whites asians change significantly study period however mortality rates increased significantly blacks apc 3 564 p value 0 001 conclusion large cohort study mortality rate cholangiocarcinoma asian patients better caucasian black patients stable mortality rates time worsening mortality among blacks indicates need address disparities health care cholangiocarcinoma research warranted understand improve outcomes patients cholangiocarcinoma google scholar","probabilities":0.9799733,"Title":"Incidence And Mortality Trends Of Cholangiocarcinoma; Are Asian Patients Different From Other Ethnicities?","Abstract":"Background\nCholangiocarcinoma is the most common biliary cancer and the second most common primary cancer of the liver. It is estimated that cholangiocarcinoma is responsible for 13% of overall cancer-related mortality worldwide. In this study, we examined the incidence and mortality temporal trends of cholangiocarcinoma since the year 2000.\nMethods\nWe used SEER 18 database to study cholangiocarcinoma cases in the US during 2000-2015. Incidence and mortality rates of cholangiocarcinoma were calculated by race and were expressed in 1,000,000 person-years. Annual percent change (APC) was calculated using joinpoint regression software.\nResults\nWe reviewed 2,191 patients with cholangiocarcinoma. Most patients were Caucasians (1,800), followed by blacks (193), Asians (182), and American Indians (16), with incidence rates of 1.643, 1.431, 1.451, and 1.199 per 100,000 person-years, respectively. The incidence rates of cholangiocarcinoma did not significantly change over the study period among Caucasians (APC=1.345, p-value =0.06), blacks (APC=1.085, p-value = 0.22), and Asians (APC=0.48, p-value = 0.76). Mortality due to cholangiocarcinoma was 1.391, 1.203, 1.194, and 1.029 per 100,000 person-years in Caucasians, blacks, Asians, and American Indians, respectively. Mortality rates of both whites and Asians did not change significantly over the study period. However, mortality rates increased significantly in Blacks (APC=3.564, p-value= 0.001).\nConclusion\nIn a large cohort study, mortality rate for cholangiocarcinoma in Asian patients is better than Caucasian and Black patients. There are stable mortality rates over time, with the worsening mortality among blacks, which indicates need to address disparities in health care for cholangiocarcinoma. More research is warranted to understand how to improve outcomes in patients with cholangiocarcinoma.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidence And Mortality Trends Of Cholangiocarcinoma; Are Asian Patients Different From Other Ethnicities? Background\nCholangiocarcinoma is the most common biliary cancer and the second most common primary cancer of the liver. It is estimated that cholangiocarcinoma is responsible for 13% of overall cancer-related mortality worldwide. In this study, we examined the incidence and mortality temporal trends of cholangiocarcinoma since the year 2000.\nMethods\nWe used SEER 18 database to study cholangiocarcinoma cases in the US during 2000-2015. Incidence and mortality rates of cholangiocarcinoma were calculated by race and were expressed in 1,000,000 person-years. Annual percent change (APC) was calculated using joinpoint regression software.\nResults\nWe reviewed 2,191 patients with cholangiocarcinoma. Most patients were Caucasians (1,800), followed by blacks (193), Asians (182), and American Indians (16), with incidence rates of 1.643, 1.431, 1.451, and 1.199 per 100,000 person-years, respectively. The incidence rates of cholangiocarcinoma did not significantly change over the study period among Caucasians (APC=1.345, p-value =0.06), blacks (APC=1.085, p-value = 0.22), and Asians (APC=0.48, p-value = 0.76). Mortality due to cholangiocarcinoma was 1.391, 1.203, 1.194, and 1.029 per 100,000 person-years in Caucasians, blacks, Asians, and American Indians, respectively. Mortality rates of both whites and Asians did not change significantly over the study period. However, mortality rates increased significantly in Blacks (APC=3.564, p-value= 0.001).\nConclusion\nIn a large cohort study, mortality rate for cholangiocarcinoma in Asian patients is better than Caucasian and Black patients. There are stable mortality rates over time, with the worsening mortality among blacks, which indicates need to address disparities in health care for cholangiocarcinoma. More research is warranted to understand how to improve outcomes in patients with cholangiocarcinoma. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prospective observational study chemotherapy induced nausea vomiting cinv hepatobiliary pancreatic cancer patients receive chemotherapy including cisplatin cinv study group japan abstract available google scholar","probabilities":0.9799733,"Title":"Prospective Observational Study On Chemotherapy-Induced Nausea And Vomiting (Cinv) For Hepatobiliary And Pancreatic Cancer Patients Who Were To Receive Chemotherapy Including Cisplatin By The Cinv Study Group Of Japan","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Prospective Observational Study On Chemotherapy-Induced Nausea And Vomiting (Cinv) For Hepatobiliary And Pancreatic Cancer Patients Who Were To Receive Chemotherapy Including Cisplatin By The Cinv Study Group Of Japan Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"glycemic index glycemic load dietary carbohydrate dietary fiber intake risk liver biliary tract cancers western europeans background type quantity dietary carbohydrate quantified glycemic index gi glycemic load gl dietary fiber may influence risk liver biliary tract cancers convincing evidence lacking patients methods association dietary gi gl carbohydrate intake hepatocellular carcinoma hcc n 191 intrahepatic bile duct ibd n 66 biliary tract n 236 cancer risk investigated 477 206 participants european prospective investigation cancer nutrition cohort dietary intake assessed country specific validated dietary questionnaires hazard ratios 95 confidence intervals estimated proportional hazard models hbv hcv status measured nested case control subset results higher dietary gi gl increased intake total carbohydrate associated liver biliary tract cancer risk hcc divergent risk estimates observed total sugar 1 43 1 17 1 74 per 50 g day total starch 0 70 0 55 0 90 per 50 g day total dietary fiber 0 70 0 52 0 93 per 10 g day findings dietary fiber confirmed among hbv hcv free participants 0 48 0 23 1 01 similar associations observed ibd dietary fiber 0 59 0 37 0 99 per 10 g day biliary tract cancer conclusions findings suggest higher consumption dietary fiber lower consumption total sugars associated lower hcc risk addition high dietary fiber intake associated lower ibd cancer risk pubmed","probabilities":0.9799733,"Title":"Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans","Abstract":"BACKGROUND: The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. PATIENTS AND METHODS: The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. RESULTS: Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. CONCLUSIONS: Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk.","Source":"PubMed","category":"HUMAN","training_data":"Glycemic index, glycemic load, dietary carbohydrate, and dietary fiber intake and risk of liver and biliary tract cancers in Western Europeans BACKGROUND: The type and quantity of dietary carbohydrate as quantified by glycemic index (GI) and glycemic load (GL), and dietary fiber may influence the risk of liver and biliary tract cancers, but convincing evidence is lacking. PATIENTS AND METHODS: The association between dietary GI/GL and carbohydrate intake with hepatocellular carcinoma (HCC; N = 191), intrahepatic bile duct (IBD; N = 66), and biliary tract (N = 236) cancer risk was investigated in 477 206 participants of the European Prospective Investigation into Cancer and Nutrition cohort. Dietary intake was assessed by country-specific, validated dietary questionnaires. Hazard ratios and 95% confidence intervals were estimated from proportional hazard models. HBV/HCV status was measured in a nested case-control subset. RESULTS: Higher dietary GI, GL, or increased intake of total carbohydrate was not associated with liver or biliary tract cancer risk. For HCC, divergent risk estimates were observed for total sugar = 1.43 (1.17-1.74) per 50 g/day, total starch = 0.70 (0.55-0.90) per 50 g/day, and total dietary fiber = 0.70 (0.52-0.93) per 10 g/day. The findings for dietary fiber were confirmed among HBV/HCV-free participants [0.48 (0.23-1.01)]. Similar associations were observed for IBD [dietary fiber = 0.59 (0.37-0.99) per 10 g/day], but not biliary tract cancer. CONCLUSIONS: Findings suggest that higher consumption of dietary fiber and lower consumption of total sugars are associated with lower HCC risk. In addition, high dietary fiber intake could be associated with lower IBD cancer risk. PubMed","prediction_labels":"HUMAN"},{"cleaned":"serum markers intrahepatic cholangiocarcinoma cholangiocarcinoma cca relatively rare type primary liver cancer originates bile duct epithelium aggressive malignancy typified unresponsiveness chemotherapy radiotherapy despite advances radiologic techniques laboratory diagnostic test diagnosis cca remains highly challenging development molecular techniques led go possible use serum markers diagnosing cholangiocarcinoma review summarizes principal characteristics serum markers cholangiocarcinoma tumour markers used frequently carbohydrate antigen 19 9 ca 19 9 carcinogenic embryonic antigen cea cancer antigen 125 shown sufficient sensitivity specificity detect monitor cca particular combination tumour markers seems increase efficiency diagnosing cholangiocarcinoma new markers soluble fragment cytokeratin 19 cyfra 21 1 mucins tumour markers formula _ 2 formula pyruvate kinase tum formula _ 2 formula pk metalloproteinase 7 mmp 7 recently shown help diagnosis cca cases prognostic value pubmed","probabilities":0.9799733,"Title":"Serum markers of intrahepatic cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers<formula>_{2}</formula> pyruvate-Kinase (TuM<formula>_{2-}</formula> PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value.","Source":"PubMed","category":"HUMAN","training_data":"Serum markers of intrahepatic cholangiocarcinoma Cholangiocarcinoma (CCA) is a relatively rare type of primary liver cancer that originates in the bile duct epithelium. It is an aggressive malignancy typified by unresponsiveness to chemotherapy and radiotherapy. Despite advances in radiologic techniques and laboratory diagnostic test, the diagnosis of CCA remains highly challenging. Development in molecular techniques has led to go into the possible use of serum markers in diagnosing of cholangiocarcinoma. This review summarizes the principal characteristics of serum markers of cholangiocarcinoma. The tumour markers used frequently such as Carbohydrate antigen 19-9 (CA 19-9), Carcinogenic Embryonic antigen (CEA), and Cancer Antigen 125 have shown sufficient sensitivity and specificity to detect and monitor CCA. In particular, the combination of these tumour markers seems to increase their efficiency in diagnosing of cholangiocarcinoma. New markers such as Soluble fragment of cytokeratin 19 (CYFRA 21-1) Mucins, Tumour Markers<formula>_{2}</formula> pyruvate-Kinase (TuM<formula>_{2-}</formula> PK) and metalloproteinase-7 (MMP-7) have been recently shown to help in the diagnosis of CCA, with in some cases a prognostic value. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact intratumoral nerve growth factor expression perineural invasion prognosis resectable extrahepatic cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Impact Of Intratumoral Nerve Growth Factor Expression On Perineural Invasion And Prognosis In Resectable Extrahepatic Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Impact Of Intratumoral Nerve Growth Factor Expression On Perineural Invasion And Prognosis In Resectable Extrahepatic Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"plasma tumor tissue mir 146a high expression correlates prolonged overall survival surgical patients intrahepatic cholangiocarcinoma purpose study investigate association tumor tissue plasma mir 146a b expressions clinicopathological properties overall survival os surgical patients intrahepatic cholangiocarcinomas icc eighty seven patients icc enrolled tumor tissue plasma sample collected mir 146a b expressions assessed quantitative polymerase chain reaction qpcr median follow duration 31 months last follow date january 2017 mir 146a p 001 mir 146b p 006 expressions tumor tissue positively associated plasma tissue mir 146a negatively correlated age p 036 poor differentiation p 020 n stage p 020 tnm stage p 007 well ecog performance p 008 whereas plasma mir 146a inversely associated n stage p 003 tnm stage p 003 ecog performance p 011 moreover tissue mir 146b negatively correlated gender p 043 stage p 047 kaplan meier curves suggested high expression tissue mir 146a p 001 plasma mir 146a p 029 correlated prolonged os nevertheless association mir 146b expression tumor tissue p 187 plasma p 336 os discovered univariate analysis indicated tissue mir 146a p 001 plasma mir 146a p 035 predict better os whereas multivariate analysis revealed tissue mir 146a p 001 high expression independent factor prolonged os plasma tissue mir 146a expression correlated favorable os whereas tissue mir 146a independent prognostic biomarker surgical patients icc pubmed","probabilities":0.7966102,"Title":"Both plasma and tumor tissue miR-146a high expression correlates with prolonged overall survival of surgical patients with intrahepatic cholangiocarcinoma","Abstract":"The purpose of this study was to investigate the association of tumor tissue and plasma miR-146a/b expressions with the clinicopathological properties and overall survival (OS) in surgical patients with intrahepatic cholangiocarcinomas (ICC).Eighty-seven patients with ICC were enrolled. Tumor tissue and plasma sample were collected and miR-146a/b expressions were assessed by quantitative polymerase chain reaction (qPCR). The median follow-up duration was 31 months, and the last follow-up date was January 2017.miR-146a (P < .001) and miR-146b (P = .006) expressions in tumor tissue were positively associated with that in plasma. Tissue miR-146a was negatively correlated with age (P = .036), poor differentiation (P = .020), N stage (P = .020), and TNM stage (P = .007), as well as ECOG performance (P = .008), whereas plasma miR-146a was inversely associated with N stage (P = .003), TNM stage (P = .003), and ECOG performance (P = .011). Moreover, tissue miR-146b was negatively correlated with gender (P = .043) and T stage (P = .047). Kaplan-Meier curves suggested that high expression of tissue miR-146a (P < .001) and plasma miR-146a (P = .029) were correlated with prolonged OS. Nevertheless, no association of miR-146b expression in tumor tissue (P = .187) and plasma (P = .336) with OS was discovered. Univariate analysis indicated that both tissue miR-146a (P < .001) and plasma miR-146a (P = .035) could predict better OS, whereas multivariate analysis revealed that only tissue miR-146a (P = .001) high expression was an independent factor for prolonged OS.Both plasma and tissue miR-146a expression correlated with favorable OS, whereas only tissue miR-146a was an independent prognostic biomarker in surgical patients with ICC.","Source":"PubMed","category":"ANIMAL","training_data":"Both plasma and tumor tissue miR-146a high expression correlates with prolonged overall survival of surgical patients with intrahepatic cholangiocarcinoma The purpose of this study was to investigate the association of tumor tissue and plasma miR-146a/b expressions with the clinicopathological properties and overall survival (OS) in surgical patients with intrahepatic cholangiocarcinomas (ICC).Eighty-seven patients with ICC were enrolled. Tumor tissue and plasma sample were collected and miR-146a/b expressions were assessed by quantitative polymerase chain reaction (qPCR). The median follow-up duration was 31 months, and the last follow-up date was January 2017.miR-146a (P < .001) and miR-146b (P = .006) expressions in tumor tissue were positively associated with that in plasma. Tissue miR-146a was negatively correlated with age (P = .036), poor differentiation (P = .020), N stage (P = .020), and TNM stage (P = .007), as well as ECOG performance (P = .008), whereas plasma miR-146a was inversely associated with N stage (P = .003), TNM stage (P = .003), and ECOG performance (P = .011). Moreover, tissue miR-146b was negatively correlated with gender (P = .043) and T stage (P = .047). Kaplan-Meier curves suggested that high expression of tissue miR-146a (P < .001) and plasma miR-146a (P = .029) were correlated with prolonged OS. Nevertheless, no association of miR-146b expression in tumor tissue (P = .187) and plasma (P = .336) with OS was discovered. Univariate analysis indicated that both tissue miR-146a (P < .001) and plasma miR-146a (P = .035) could predict better OS, whereas multivariate analysis revealed that only tissue miR-146a (P = .001) high expression was an independent factor for prolonged OS.Both plasma and tissue miR-146a expression correlated with favorable OS, whereas only tissue miR-146a was an independent prognostic biomarker in surgical patients with ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"identification s100 calcium binding protein a9 prognostic biomarker gallbladder cancer background gallbladder cancer gbc lethal orphan malignancy biliary tract poor prognosis varied global incidences predominately reported northern india moreover early diagnostic biomarker gbc still undetermined earlier studies demonstrated s100a9 associated prognosis various malignancies s100a9 calgranulin b myeloid related protein 14 calcium binding protein wide range possible intracellular well extracellular functions previous reports showed s100a9 stimulates malignant development cancer progression also involved inflammatory diseases far study made expression epigenetic regulation s100a9 gbc therefore present study aimed investigate expression promoter methylation status s100a9 gbc evaluate utility diagnostic biomarker gbc materials method methylation specific pcr ms pcr done determine methylation status s100a9 gene promoter semi quantitative quantitative rt pcr performed assess expression level tumor non tumor tissues immunohistochemistry ihc carried understand cellular distribution statistical analysis performed using student test paired case control tissue samples one way anova multiple comparison procedures results ms pcr s100a9 showed methylation p 0 022 promoter region e 75 9 12 adjacent non tumor ant tissues 25 3 12 gbc cases rt pcr analyses revealed upregulation s100a9 gbc transcriptional level ihc analysis supported change transcriptional level scored positive s100a9 62 36 58 gbc 40 12 30 non tumor p 0 048 conclusion study shows elevated expression hypomethylation s100a9 gene promoter suggesting dna methylation plays crucial role regulation s100a9 expression gbc however studies warranted confirm larger pool samples concluding usefulness biomarker gbc google scholar","probabilities":0.88235295,"Title":"Identification Of S100 Calcium Binding Protein A9 As A Prognostic Biomarker In Gallbladder Cancer","Abstract":"Background\nGallbladder cancer (GBC) is the most lethal orphan malignancy of biliary tract, with poor prognosis and varied global incidences, predominately reported from, Northern India. Moreover, early diagnostic biomarker(s) of GBC is still undetermined. Earlier studies have demonstrated that S100A9 is associated with the prognosis of various malignancies. S100A9 (calgranulin B or Myeloid Related Protein-14) is a calcium binding protein which has wide range of possible intracellular as well as extracellular functions. Previous reports showed that S100A9 stimulates malignant development and cancer progression, and is also involved in other inflammatory diseases. So far, no study has been made on the expression and epigenetic regulation of S100A9 in GBC. Therefore, the present study aimed to investigate the expression and promoter methylation status of S100A9 in GBC to evaluate its utility as a diagnostic biomarker for GBC.\nMaterials and method\nMethylation specific PCR (MS-PCR) was done to determine the methylation status of S100A9 gene promoter. Semi quantitative and quantitative RT-PCR were performed to assess its expression level in tumor and non tumor tissues. Immunohistochemistry (IHC) was carried out to understand its cellular distribution. Statistical analysis was performed using student’s t-test for paired case and control tissue samples, and one way ANOVA for multiple comparison procedures.\nResults\nMS-PCR of S100A9 showed methylation (p =0.022) in the promoter region of about i.e.,75% (9/12) in adjacent non tumor (ANT) tissues and about 25% (3/12) in GBC cases. RT-PCR analyses revealed upregulation of S100A9 in GBC at transcriptional level. IHC analysis further supported the change in the transcriptional level, scored positive for S100A9 (62%; 36/58), in GBC and about (40%; 12/30) in non tumor (p <0.048).\nConclusion\nThe study shows that elevated expression and hypomethylation in the S100A9 gene promoter suggesting that DNA methylation plays a crucial role in the regulation of S100A9 expression in GBC. However, further studies are warranted to confirm this in larger pool of samples before concluding its usefulness as a biomarker of GBC.","Source":"Google Scholar","category":"HUMAN","training_data":"Identification Of S100 Calcium Binding Protein A9 As A Prognostic Biomarker In Gallbladder Cancer Background\nGallbladder cancer (GBC) is the most lethal orphan malignancy of biliary tract, with poor prognosis and varied global incidences, predominately reported from, Northern India. Moreover, early diagnostic biomarker(s) of GBC is still undetermined. Earlier studies have demonstrated that S100A9 is associated with the prognosis of various malignancies. S100A9 (calgranulin B or Myeloid Related Protein-14) is a calcium binding protein which has wide range of possible intracellular as well as extracellular functions. Previous reports showed that S100A9 stimulates malignant development and cancer progression, and is also involved in other inflammatory diseases. So far, no study has been made on the expression and epigenetic regulation of S100A9 in GBC. Therefore, the present study aimed to investigate the expression and promoter methylation status of S100A9 in GBC to evaluate its utility as a diagnostic biomarker for GBC.\nMaterials and method\nMethylation specific PCR (MS-PCR) was done to determine the methylation status of S100A9 gene promoter. Semi quantitative and quantitative RT-PCR were performed to assess its expression level in tumor and non tumor tissues. Immunohistochemistry (IHC) was carried out to understand its cellular distribution. Statistical analysis was performed using student’s t-test for paired case and control tissue samples, and one way ANOVA for multiple comparison procedures.\nResults\nMS-PCR of S100A9 showed methylation (p =0.022) in the promoter region of about i.e.,75% (9/12) in adjacent non tumor (ANT) tissues and about 25% (3/12) in GBC cases. RT-PCR analyses revealed upregulation of S100A9 in GBC at transcriptional level. IHC analysis further supported the change in the transcriptional level, scored positive for S100A9 (62%; 36/58), in GBC and about (40%; 12/30) in non tumor (p <0.048).\nConclusion\nThe study shows that elevated expression and hypomethylation in the S100A9 gene promoter suggesting that DNA methylation plays a crucial role in the regulation of S100A9 expression in GBC. However, further studies are warranted to confirm this in larger pool of samples before concluding its usefulness as a biomarker of GBC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"relationship intracholecystic papillary tubular neoplasms invasive carcinoma gallbladder introduction term intracholecystic papillary tubular neoplasm icpn suggested authors group exophytic lesions gallbladder study demographic pathological immunohistochemical features 45 icpn cases relationship invasive carcinoma analyzed material methods total 45 icpn cases retrieved 7334 cholecystectomies performed between1996 2014 cases evaluated regard demographic pathological immunohistochemical features correlation clinical histopathological data occurrence invasion sought results incidence icpn 0 61 series invasive carcinoma observed 56 cases factors associated invasion diffuse high grade dysplasia p 002 papillary growth pattern p 001 greatest diameter lesion high ki67 proliferation index p 0001 discussion authors reported small intracholecystic exophytic lesions without high grade dysplasia considered inconsequential however enough data concerning features large lesions high grade dysplasia prognoses data suggest cases diffuse high grade dysplasia tubulopapillary papillary growth pattern large tumor size high ki67 proliferation index studied presence invasion pubmed","probabilities":0.9799733,"Title":"The Relationship Between Intracholecystic Papillary-Tubular Neoplasms and Invasive Carcinoma of the Gallbladder","Abstract":"INTRODUCTION: The term intracholecystic papillary-tubular neoplasm (ICPN) is suggested by some authors for a group of exophytic lesions of the gallbladder. In our study, demographic, pathological, and immunohistochemical features of 45 ICPN cases and their relationship with invasive carcinoma were analyzed. MATERIAL AND METHODS: A total of 45 ICPN cases were retrieved out of 7334 cholecystectomies performed between1996 and 2014. Cases were evaluated with regard to demographic, pathological, and immunohistochemical features. Correlation between the clinical and histopathological data and occurrence of invasion was sought. RESULTS: The incidence of ICPN was 0.61% in our series. Invasive carcinoma was observed in 56% of cases. Factors associated with invasion were diffuse high-grade dysplasia (P = .002), papillary growth pattern (P = .001), greatest diameter of the lesion, and high Ki67 proliferation index (P < .0001). DISCUSSION: Some authors have reported that small intracholecystic exophytic lesions without high-grade dysplasia are considered to be inconsequential. However, there are not enough data concerning the features of large lesions with high-grade dysplasia and their prognoses. Our data suggest that cases with diffuse high-grade dysplasia and tubulopapillary/papillary growth pattern, large tumor size, and high Ki67 proliferation index should be studied for the presence of invasion.","Source":"PubMed","category":"HUMAN","training_data":"The Relationship Between Intracholecystic Papillary-Tubular Neoplasms and Invasive Carcinoma of the Gallbladder INTRODUCTION: The term intracholecystic papillary-tubular neoplasm (ICPN) is suggested by some authors for a group of exophytic lesions of the gallbladder. In our study, demographic, pathological, and immunohistochemical features of 45 ICPN cases and their relationship with invasive carcinoma were analyzed. MATERIAL AND METHODS: A total of 45 ICPN cases were retrieved out of 7334 cholecystectomies performed between1996 and 2014. Cases were evaluated with regard to demographic, pathological, and immunohistochemical features. Correlation between the clinical and histopathological data and occurrence of invasion was sought. RESULTS: The incidence of ICPN was 0.61% in our series. Invasive carcinoma was observed in 56% of cases. Factors associated with invasion were diffuse high-grade dysplasia (P = .002), papillary growth pattern (P = .001), greatest diameter of the lesion, and high Ki67 proliferation index (P < .0001). DISCUSSION: Some authors have reported that small intracholecystic exophytic lesions without high-grade dysplasia are considered to be inconsequential. However, there are not enough data concerning the features of large lesions with high-grade dysplasia and their prognoses. Our data suggest that cases with diffuse high-grade dysplasia and tubulopapillary/papillary growth pattern, large tumor size, and high Ki67 proliferation index should be studied for the presence of invasion. PubMed","prediction_labels":"HUMAN"},{"cleaned":"adiposity gastrointestinal cancers epidemiology mechanisms future directions excess adiposity risk factor several cancers gastrointestinal system specifically oesophageal adenocarcinoma colorectal small intestine pancreatic liver gallbladder stomach cancers increasing prevalence obesity nearly regions world relationship represent growing source cancers digestive system experimental molecular epidemiological studies indicate important roles alterations insulin signalling adipose tissue derived inflammation sex hormone pathways mediating association adiposity gastrointestinal cancer intestinal microbiome gut hormones non alcoholic fatty liver disease nafld also possible roles however important gaps remain knowledge instance understanding adiposity throughout life course related risk gastrointestinal cancer development obesity influences gastrointestinal cancer prognosis survival limited nonetheless increasing use state art analytical methods omics technologies mendelian randomization mri large scale epidemiological studies offers exciting opportunities advance understanding complex relationship adiposity gastrointestinal cancers examine epidemiology associations obesity gastrointestinal cancer explore potential mechanisms underlying relationships highlight important unanswered research questions pubmed","probabilities":0.7966102,"Title":"Adiposity and gastrointestinal cancers: epidemiology, mechanisms and future directions","Abstract":"Excess adiposity is a risk factor for several cancers of the gastrointestinal system, specifically oesophageal adenocarcinoma and colorectal, small intestine, pancreatic, liver, gallbladder and stomach cancers. With the increasing prevalence of obesity in nearly all regions of the world, this relationship could represent a growing source of cancers of the digestive system. Experimental and molecular epidemiological studies indicate important roles for alterations in insulin signalling, adipose tissue-derived inflammation and sex hormone pathways in mediating the association between adiposity and gastrointestinal cancer. The intestinal microbiome, gut hormones and non alcoholic fatty liver disease (NAFLD) also have possible roles. However, important gaps remain in our knowledge. For instance, our understanding of how adiposity throughout the life course is related to the risk of gastrointestinal cancer development and of how obesity influences gastrointestinal cancer prognosis and survival is limited. Nonetheless, the increasing use of state-of-the-art analytical methods (such as omics technologies, Mendelian randomization and MRI) in large-scale epidemiological studies offers exciting opportunities to advance our understanding of the complex relationship between adiposity and gastrointestinal cancers. Here, we examine the epidemiology of associations between obesity and gastrointestinal cancer, explore potential mechanisms underlying these relationships and highlight important unanswered research questions.","Source":"PubMed","category":"HUMAN","training_data":"Adiposity and gastrointestinal cancers: epidemiology, mechanisms and future directions Excess adiposity is a risk factor for several cancers of the gastrointestinal system, specifically oesophageal adenocarcinoma and colorectal, small intestine, pancreatic, liver, gallbladder and stomach cancers. With the increasing prevalence of obesity in nearly all regions of the world, this relationship could represent a growing source of cancers of the digestive system. Experimental and molecular epidemiological studies indicate important roles for alterations in insulin signalling, adipose tissue-derived inflammation and sex hormone pathways in mediating the association between adiposity and gastrointestinal cancer. The intestinal microbiome, gut hormones and non alcoholic fatty liver disease (NAFLD) also have possible roles. However, important gaps remain in our knowledge. For instance, our understanding of how adiposity throughout the life course is related to the risk of gastrointestinal cancer development and of how obesity influences gastrointestinal cancer prognosis and survival is limited. Nonetheless, the increasing use of state-of-the-art analytical methods (such as omics technologies, Mendelian randomization and MRI) in large-scale epidemiological studies offers exciting opportunities to advance our understanding of the complex relationship between adiposity and gastrointestinal cancers. Here, we examine the epidemiology of associations between obesity and gastrointestinal cancer, explore potential mechanisms underlying these relationships and highlight important unanswered research questions. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological significance altered notch signaling extrahepatic cholangiocarcinoma gallbladder carcinoma aim investigate role clinicopathological significance aberrant expression notch receptors delta like ligand 4 dll4 extrahepatic cholangiocarcinoma gallbladder carcinoma methods one hundred ten patients surgically resected extrahepatic cholangiocarcinoma cc gallbladder carcinoma specimens examined immunohistochemistry available paraffin blocks immunohistochemistry performed using anti notch receptors 1 4 anti dll4 antibodies scored immunopositivity notch receptors dll4 expression percentage positive tumor cells cytoplasmic expression intensity immunostaining coexistent nuclear localization evaluated clinicopathological parameters survival data compared expression notch receptors 1 4 dll4 results notch receptor proteins showed cytoplasm without nuclear expression cancer cells well showing weak cytoplasmic expression non neoplastic cells semiquantitative evaluation positive immunostaining notch receptor 1 detected 96 cases 87 3 notch receptor 2 97 88 2 notch receptor 3 97 88 2 notch receptor 4 103 93 6 dll4 84 76 4 addition coexistent nuclear localization noted notch receptor 1 18 cases 18 8 notch receptor 2 40 41 2 notch receptor 3 32 33 0 notch receptor 4 99 96 1 dll4 48 57 1 notch receptor 1 expression correlated advanced tumor node metastasis tnm stage p 0 043 notch receptor 3 advanced stage p 0 017 tendency express cases nodal metastasis p 0 065 advanced tnm stage p 0 052 dll4 expression tended related less histological differentiation p 0 095 coexistent nuclear localization notch receptor 3 related nodal metastasis p 0 027 notch receptor 4 less histological differentiation p 0 036 dll4 tended related inversely stage p 0 053 coexistent nuclear localization dll4 related poor survival p 0 002 conclusion aberrant expression notch receptors 1 3 play role cancer progression cytoplasmic nuclear coexistence dll4 expression correlates poor survival extrahepatic cc gallbladder carcinoma stn","probabilities":0.9799733,"Title":"Clinicopathological Significance Of Altered Notch Signaling In Extrahepatic Cholangiocarcinoma And Gallbladder Carcinoma","Abstract":"Aim: To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma. \n\n Methods: One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4. \n\n Results: Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T stage (P = 0.053). Coexistent nuclear localization of DLL4 was related to poor survival (P = 0.002). \n\n Conclusion: Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma.","Source":"STN","category":"HUMAN","training_data":"Clinicopathological Significance Of Altered Notch Signaling In Extrahepatic Cholangiocarcinoma And Gallbladder Carcinoma Aim: To investigate the role and clinicopathological significance of aberrant expression of Notch receptors and Delta-like ligand-4 (DLL4) in extrahepatic cholangiocarcinoma and gallbladder carcinoma. \n\n Methods: One hundred and ten patients had surgically resected extrahepatic cholangiocarcinoma (CC) and gallbladder carcinoma specimens examined by immunohistochemistry of available paraffin blocks. Immunohistochemistry was performed using anti-Notch receptors 1-4 and anti-DLL4 antibodies. We scored the immunopositivity of Notch receptors and DLL4 expression by percentage of positive tumor cells with cytoplasmic expression and intensity of immunostaining. Coexistent nuclear localization was evaluated. Clinicopathological parameters and survival data were compared with the expression of Notch receptors 1-4 and DLL4. \n\n Results: Notch receptor proteins showed in the cytoplasm with or without nuclear expression in cancer cells, as well as showing weak cytoplasmic expression in non-neoplastic cells. By semiquantitative evaluation, positive immunostaining of Notch receptor 1 was detected in 96 cases (87.3%), Notch receptor 2 in 97 (88.2%), Notch receptor 3 in 97 (88.2%), Notch receptor 4 in 103 (93.6), and DLL4 in 84 (76.4%). In addition, coexistent nuclear localization was noted [Notch receptor 1; 18 cases (18.8%), Notch receptor 2; 40 (41.2%), Notch receptor 3; 32 (33.0%), Notch receptor 4; 99 (96.1%), DLL4; 48 (57.1%)]. Notch receptor 1 expression was correlated with advanced tumor, node, metastasis (TNM) stage (P = 0.043), Notch receptor 3 with advanced T stage (P = 0.017), tendency to express in cases with nodal metastasis (P = 0.065) and advanced TNM stage (P = 0.052). DLL4 expression tended to be related to less histological differentiation (P = 0.095). Coexistent nuclear localization of Notch receptor 3 was related to no nodal metastasis (P = 0.027) and Notch receptor 4 with less histological differentiation (P = 0.036), while DLL4 tended to be related inversely with T stage (P = 0.053). Coexistent nuclear localization of DLL4 was related to poor survival (P = 0.002). \n\n Conclusion: Aberrant expression of Notch receptors 1 and 3 play a role during cancer progression, and cytoplasmic nuclear coexistence of DLL4 expression correlates with poor survival in extrahepatic CC and gallbladder carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"surgical treatment prognostic analysis 93 cases hilar cholangiocarcinoma objective explore surgical treatment prognosis hilar cholangiocarcinoma methods retrospective study 93 cases hilar cholangiocarcinoma treated surgically hospital june 1999 june 2005 prognostic factors also analyzed results fifty two cases treated curative resection 21 palliative resection 9 nonoperative drainage eleven cases underwent palliative drainage operations median survive time 31 months curative resection group 13 7 months palliative resection group 11 months nonoperative drainage group patient age serum total bilirubin clinical type bismuth corlette tumor differentiation lymph node metastases important factors predicting prognosis hilar cholangiocarcinoma conclusions resection main treatment hilar cholangiocarcinoma curative resection best way obtain better prognosis age preoperative serum total bilirubin bismuth clinical type tumor histopathological grading lymph node metastases considered significant effect prognosis stn","probabilities":0.9799733,"Title":"Surgical Treatment And Prognostic Analysis Of 93 Cases Of Hilar Cholangiocarcinoma","Abstract":"Objective: To explore the surgical treatment and prognosis of hilar cholangiocarcinoma. \n\n Methods: This was a retrospective study of 93 cases of hilar cholangiocarcinoma that were treated surgically at our hospital from June 1999 to June 2005. Prognostic factors were also analyzed. \n\n Results: Fifty-two cases were treated with curative resection, 21 with palliative resection, and 9 with nonoperative drainage. Eleven cases underwent palliative drainage operations. The median survive time was 31 months in the curative resection group, 13.7 months in the palliative resection group, and 11 months in the nonoperative drainage group. Patient age, serum total bilirubin, clinical type of Bismuth-Corlette, tumor differentiation, and lymph node metastases were important factors for predicting the prognosis of hilar cholangiocarcinoma. \n\n Conclusions: Resection was the main treatment for hilar cholangiocarcinoma, and curative resection was the best way to obtain better prognosis. Age, preoperative serum total bilirubin, bismuth clinical type, tumor histopathological grading, and lymph node metastases were considered to have a significant effect on prognosis.","Source":"STN","category":"HUMAN","training_data":"Surgical Treatment And Prognostic Analysis Of 93 Cases Of Hilar Cholangiocarcinoma Objective: To explore the surgical treatment and prognosis of hilar cholangiocarcinoma. \n\n Methods: This was a retrospective study of 93 cases of hilar cholangiocarcinoma that were treated surgically at our hospital from June 1999 to June 2005. Prognostic factors were also analyzed. \n\n Results: Fifty-two cases were treated with curative resection, 21 with palliative resection, and 9 with nonoperative drainage. Eleven cases underwent palliative drainage operations. The median survive time was 31 months in the curative resection group, 13.7 months in the palliative resection group, and 11 months in the nonoperative drainage group. Patient age, serum total bilirubin, clinical type of Bismuth-Corlette, tumor differentiation, and lymph node metastases were important factors for predicting the prognosis of hilar cholangiocarcinoma. \n\n Conclusions: Resection was the main treatment for hilar cholangiocarcinoma, and curative resection was the best way to obtain better prognosis. Age, preoperative serum total bilirubin, bismuth clinical type, tumor histopathological grading, and lymph node metastases were considered to have a significant effect on prognosis. STN","prediction_labels":"HUMAN"},{"cleaned":"epigenetic profiling gallbladder cancer gall stone diseases evaluation role tumour associated genes background today global mortality rate gallbladder cancer still high genetic epigenetic alterations play pivotal roles development cancer selected seven tumour associated genes implicated cancers assess methylation status gallbladder cancer gallstone diseases aim study study promoter methylation certain tumour associated genes molecular pathogenesis gallbladder cancer gall stone diseases materials methods methylation specific pcr seven tumour associated genes viz maspin 14 3 3 sigma gene thbs1 flnc hltf cox 2 socs1 performed 50 gallbladder cancer gbc 30 gall stone diseases gsd respective adjacent control tissues semi quantitative pcr immunohistochemistry carried check expression level student test carried compare differences methylation expression patterns cases control tissues results observed methylation cpg islands seven studied markers frequency methylation found varying among different samples 14 33 sigma showed methylation 45 gbc 90 p 0 0001 25 gsd 86 66 p 0 001 maspin 35 gbc 70 p 0 0008 18 gsd 51 43 p 0 040 flnc 16 gbc 32 p 0 0044 9 gsd 25 71 p ns thbs1 26 gbc 52 p 0 0009 10 gsd 28 57 p 0 0505 hltf 8 gbc 16 p ns 2 gsd 5 71 p ns cox2 10 gbc 20 p ns 6 gsd 17 14 p ns socs 1 3 gbc samples 6 p ns gsd semi quantitative pcr revealed regulation maspin 14 3 3 sigma thbs1 hltf cox2 socs1 advanced gallbladder cases immunohistochemistry confirmed regulation socs1 gbc conclusion present study infers accumulation epigenetic alterations increases poor prognosis gbc patients seven genes maspin thbs1 play key epigenetic role gbc gsd reason downregulation socs1 gbc unaltered expression 14 3 3 sigma protein gbc gsd tissue samples clear investigation expression pattern genes gbc cell lines may elucidate likely functional role association gallbladder cancer stn","probabilities":1.0,"Title":"Epigenetic Profiling Of Gallbladder Cancer And Gall Stone Diseases: Evaluation Of Role Of Tumour Associated Genes","Abstract":"Background: As on today, the global mortality rate of gallbladder cancer is still very high. Both genetic and epigenetic alterations play pivotal roles in the development of cancer. We selected seven tumour associated genes, implicated in other cancers, to assess their methylation status in gallbladder cancer and gallstone diseases. \r\n\r\n Aim of study: To study the promoter methylation of certain tumour associated genes in the molecular pathogenesis of gallbladder cancer and gall stone diseases. \r\n\r\n Materials and methods: Methylation specific PCR for seven tumour associated genes, viz., MASPIN, 14-3-3 sigma gene, THBS1, FLNC, HLTF, COX-2 and SOCS1, was performed in 50 gallbladder cancer (GBC), 30 gall stone diseases (GSD) and their respective adjacent control tissues. Semi-quantitative PCR and immunohistochemistry was carried out to check the expression level. Student's t-test was carried out to compare the differences in the methylation and expression patterns between cases and control tissues. \r\n\r\n Results: We observed methylation of CpG islands in seven of the studied markers, but, the frequency of methylation was found varying among different samples. Of them, 14-33 sigma showed methylation in 45 GBC (90%; p=0.0001) and 25 GSD (86.66%; p=0.001), MASPIN in 35 GBC (70%; p=0.0008) and 18 GSD (51.43%; p=0.040), FLNC in 16 GBC (32%; p=0.0044) and 9 GSD (25.71%; p=ns), THBS1 in 26 GBC (52%; p=0.0009) and 10 GSD (28.57%; p=0.0505), HLTF in 8 GBC (16%; p=ns) and 2 GSD (5.71%; p=ns), COX2 in 10 GBC (20%; p=ns) and 6 GSD (17.14%; p=ns) and SOCS-1 in 3 GBC samples only (6%; p=ns), but not in GSD. Semi-quantitative PCR revealed down regulation in MASPIN, 14-3-3 sigma, THBS1, HLTF, COX2 and SOCS1 in advanced gallbladder cases. Immunohistochemistry further confirmed the down-regulation of SOCS1 in GBC. \r\n\r\n Conclusion: The present study infers that accumulation of epigenetic alterations increases poor prognosis of GBC patients. Out of seven genes, MASPIN and THBS1 play key epigenetic role in GBC, but not in GSD. The reason for downregulation of SOCS1 only in GBC, and unaltered expression of 14-3-3 sigma protein in all the GBC and GSD tissue samples is not clear. Further investigation on the expression pattern of these genes in GBC cell lines may elucidate their likely functional role in in association with gallbladder cancer.","Source":"STN","category":"ANIMAL","training_data":"Epigenetic Profiling Of Gallbladder Cancer And Gall Stone Diseases: Evaluation Of Role Of Tumour Associated Genes Background: As on today, the global mortality rate of gallbladder cancer is still very high. Both genetic and epigenetic alterations play pivotal roles in the development of cancer. We selected seven tumour associated genes, implicated in other cancers, to assess their methylation status in gallbladder cancer and gallstone diseases. \r\n\r\n Aim of study: To study the promoter methylation of certain tumour associated genes in the molecular pathogenesis of gallbladder cancer and gall stone diseases. \r\n\r\n Materials and methods: Methylation specific PCR for seven tumour associated genes, viz., MASPIN, 14-3-3 sigma gene, THBS1, FLNC, HLTF, COX-2 and SOCS1, was performed in 50 gallbladder cancer (GBC), 30 gall stone diseases (GSD) and their respective adjacent control tissues. Semi-quantitative PCR and immunohistochemistry was carried out to check the expression level. Student's t-test was carried out to compare the differences in the methylation and expression patterns between cases and control tissues. \r\n\r\n Results: We observed methylation of CpG islands in seven of the studied markers, but, the frequency of methylation was found varying among different samples. Of them, 14-33 sigma showed methylation in 45 GBC (90%; p=0.0001) and 25 GSD (86.66%; p=0.001), MASPIN in 35 GBC (70%; p=0.0008) and 18 GSD (51.43%; p=0.040), FLNC in 16 GBC (32%; p=0.0044) and 9 GSD (25.71%; p=ns), THBS1 in 26 GBC (52%; p=0.0009) and 10 GSD (28.57%; p=0.0505), HLTF in 8 GBC (16%; p=ns) and 2 GSD (5.71%; p=ns), COX2 in 10 GBC (20%; p=ns) and 6 GSD (17.14%; p=ns) and SOCS-1 in 3 GBC samples only (6%; p=ns), but not in GSD. Semi-quantitative PCR revealed down regulation in MASPIN, 14-3-3 sigma, THBS1, HLTF, COX2 and SOCS1 in advanced gallbladder cases. Immunohistochemistry further confirmed the down-regulation of SOCS1 in GBC. \r\n\r\n Conclusion: The present study infers that accumulation of epigenetic alterations increases poor prognosis of GBC patients. Out of seven genes, MASPIN and THBS1 play key epigenetic role in GBC, but not in GSD. The reason for downregulation of SOCS1 only in GBC, and unaltered expression of 14-3-3 sigma protein in all the GBC and GSD tissue samples is not clear. Further investigation on the expression pattern of these genes in GBC cell lines may elucidate their likely functional role in in association with gallbladder cancer. STN","prediction_labels":"ANIMAL"},{"cleaned":"upregulation dpy30 promotes cell proliferation predicts poor prognosis cholangiocarcinoma objectives modification lysine 4 histone h3 methylation set1 mll family methyltransferase complexes tightly linked cancer progression dpy30 important subunit set1 mll complexes however expression roles cancer progression little known especially cholangiocarcinoma cca materials methods q pcr ihc performed detect levels dpy30 mrna protein cca tissues effect dpy30 knockdown proliferation cca cells detected mts colony formation cell cycle distribution analyzed flow cytometer glucose uptake lactate release atp production assays performed detect glycolysis cca cells results level dpy30 mrna protein cca tissues significantly higher pericancer tissues upregulation closely associated pathological differentiation tumor size tnm stage addition kaplan meier analysis overall survival revealed dpy30 upregulation significantly associated poor survival univariate multivariate analysis indicated independently prognosis factor cca patients moreover dpy30 knockdown inhibited vitro growth induced cell cycle arrest g2 m decreased glycolysis cca cells conclusions dpy30 upregulation may promote development cca associated aggressive malignant behavior poor survival outcome cca patients dpy30 might serve potential novel target treatment cca patients stn","probabilities":0.9467213,"Title":"Upregulation Of Dpy30 Promotes Cell Proliferation And Predicts A Poor Prognosis In Cholangiocarcinoma","Abstract":"Objectives: Modification of lysine 4 on histone H3 methylation by SET1 and MLL family methyltransferase complexes is tightly linked to cancer progression. DPY30 is an important subunit of SET1 and MLL complexes, however, its expression and roles in cancer progression was little known, especially in cholangiocarcinoma (CCA). \r\n\r\n Materials and methods: The Q-PCR and IHC were performed to detect the levels of DPY30 mRNA and protein in CCA tissues. Effect of DPY30 knockdown on the proliferation of CCA cells was detected by MTS and colony formation, and cell cycle distribution was analyzed by flow cytometer. The glucose uptake, lactate release and ATP production assays were performed to detect the glycolysis of CCA cells. \r\n\r\n Results: The level of DPY30 mRNA and protein in CCA tissues were all significantly higher than that of pericancer tissues, and its upregulation was closely associated with pathological differentiation, tumor size, and TNM stage. In addition, Kaplan-Meier analysis of overall survival revealed that DPY30 upregulation was significantly associated with poor survival, and univariate and multivariate analysis indicated that it was an independently prognosis factor in CCA patients. Moreover, DPY30 knockdown inhibited in-vitro growth and induced cell cycle arrest at G2/M and decreased glycolysis in CCA cells. \r\n\r\n Conclusions: DPY30 upregulation may promote the development of CCA and was associated with the aggressive malignant behavior and poor survival outcome of CCA patients. DPY30 might serve as a potential novel target for treatment of CCA patients.","Source":"STN","category":"ANIMAL","training_data":"Upregulation Of Dpy30 Promotes Cell Proliferation And Predicts A Poor Prognosis In Cholangiocarcinoma Objectives: Modification of lysine 4 on histone H3 methylation by SET1 and MLL family methyltransferase complexes is tightly linked to cancer progression. DPY30 is an important subunit of SET1 and MLL complexes, however, its expression and roles in cancer progression was little known, especially in cholangiocarcinoma (CCA). \r\n\r\n Materials and methods: The Q-PCR and IHC were performed to detect the levels of DPY30 mRNA and protein in CCA tissues. Effect of DPY30 knockdown on the proliferation of CCA cells was detected by MTS and colony formation, and cell cycle distribution was analyzed by flow cytometer. The glucose uptake, lactate release and ATP production assays were performed to detect the glycolysis of CCA cells. \r\n\r\n Results: The level of DPY30 mRNA and protein in CCA tissues were all significantly higher than that of pericancer tissues, and its upregulation was closely associated with pathological differentiation, tumor size, and TNM stage. In addition, Kaplan-Meier analysis of overall survival revealed that DPY30 upregulation was significantly associated with poor survival, and univariate and multivariate analysis indicated that it was an independently prognosis factor in CCA patients. Moreover, DPY30 knockdown inhibited in-vitro growth and induced cell cycle arrest at G2/M and decreased glycolysis in CCA cells. \r\n\r\n Conclusions: DPY30 upregulation may promote the development of CCA and was associated with the aggressive malignant behavior and poor survival outcome of CCA patients. DPY30 might serve as a potential novel target for treatment of CCA patients. STN","prediction_labels":"ANIMAL"},{"cleaned":"targeting pi3k akt mtor pathway biliary tract cancers review current evidences future perspectives biliary tract cancers btcs group invasive neoplasms increasing incidence dismal prognosis advanced disease standard care represented first line chemotherapy cisplatin gemcitabine subsequent lines clear recommendations currently available highlighting need novel therapeutic approaches pi3k akt mtor pathway core regulator cell metabolism growth survival involved btcs carcinogenesis progression mutations gene copy number alterations aberrant protein phosphorylation pi3k akt mtor pten thoroughly described btcs correlate poor survival outcomes several pre clinical evidences state efficacy pi3k akt mtor pathway inhibitors btcs vitro vivo clinical setting initial studies rapamycin analogs shown interesting activity acceptable toxicity profile novel strategies evaluating akt pi3k inhibitors risen serious safety concerns pointing need improved patient selection increased target specificity clinical development agents alone combination chemotherapy review extensively describes role pi3k akt mtor pathway btcs examines rationale targeting tumors particular focus clinical activity toxicities perspectives development pi3k akt mtor pathway inhibitors pubmed","probabilities":0.875,"Title":"Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives","Abstract":"Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches. The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes. Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy. This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.","Source":"PubMed","category":"ANIMAL","training_data":"Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches. The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes. Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy. This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"absolute neutrophil count predicts postoperative prognosis mass forming intrahepatic cholangiocarcinoma background aim intrahepatic cholangiocarcinoma ihcc characterized poor prognosis postoperative recurrence remains problem thus prognostic markers ihcc greatly needed recently inflammatory factors reported related tumor progression recurrence various cancers therefore present study aimed evaluate prognostic ability inflammatory factors materials methods forty four patients mass forming ihcc m ihcc retrospectively evaluated correlations inflammatory markers including neutrophil lymphocyte ratio modified glasgow prognostic score patient survival assessed results absolute neutrophil count anc significantly higher recurrence group non recurrence group p 0 00568 significant prognostic factor multivariate analysis poor recurrence free survival rfs p 0 00452 cancer specific survival css p 0 0323 associated high neutrophil levels moreover neutrophil infiltration tumor site positively correlated anc conclusion anc associated poor rfs used predict recurrence patients m ihcc pubmed","probabilities":0.9799733,"Title":"Absolute Neutrophil Count Predicts Postoperative Prognosis in Mass-forming Intrahepatic Cholangiocarcinoma","Abstract":"BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (IHCC) is characterized by poor prognosis, and postoperative recurrence remains a problem. Thus, prognostic markers for IHCC are greatly needed. Recently, inflammatory factors were reported to be related to tumor progression and recurrence in various cancers. Therefore, the present study aimed to evaluate the prognostic ability of inflammatory factors. MATERIALS AND METHODS: Forty-four patients with mass-forming IHCC (m-IHCC) were retrospectively evaluated and the correlations between inflammatory markers, including neutrophil-to-lymphocyte ratio and, modified Glasgow prognostic score, and patient survival were assessed. RESULTS: The absolute neutrophil count (ANC) was significantly higher in the recurrence group than in the non-recurrence group (p=0.00568) and the most significant prognostic factor by multivariate analysis. Poor recurrence-free survival (RFS; p=0.00452) and cancer-specific survival (CSS; p=0.0323) were associated with high neutrophil levels. Moreover, neutrophil infiltration in the tumor site was positively correlated with ANC. CONCLUSION: ANC is associated with poor RFS, and could be used to predict recurrence in patients with m-IHCC.","Source":"PubMed","category":"HUMAN","training_data":"Absolute Neutrophil Count Predicts Postoperative Prognosis in Mass-forming Intrahepatic Cholangiocarcinoma BACKGROUND/AIM: Intrahepatic cholangiocarcinoma (IHCC) is characterized by poor prognosis, and postoperative recurrence remains a problem. Thus, prognostic markers for IHCC are greatly needed. Recently, inflammatory factors were reported to be related to tumor progression and recurrence in various cancers. Therefore, the present study aimed to evaluate the prognostic ability of inflammatory factors. MATERIALS AND METHODS: Forty-four patients with mass-forming IHCC (m-IHCC) were retrospectively evaluated and the correlations between inflammatory markers, including neutrophil-to-lymphocyte ratio and, modified Glasgow prognostic score, and patient survival were assessed. RESULTS: The absolute neutrophil count (ANC) was significantly higher in the recurrence group than in the non-recurrence group (p=0.00568) and the most significant prognostic factor by multivariate analysis. Poor recurrence-free survival (RFS; p=0.00452) and cancer-specific survival (CSS; p=0.0323) were associated with high neutrophil levels. Moreover, neutrophil infiltration in the tumor site was positively correlated with ANC. CONCLUSION: ANC is associated with poor RFS, and could be used to predict recurrence in patients with m-IHCC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"expression smad7 cholangiocarcinoma prognostic significance implications tumor metastasis background molecular markers known predict cholangiocarcinoma cca prognosis smad7 certain relationship epithelial mesenchymal transition emt relevance cca unclear therefore expression clinical significance smad7 cca focus study methods expression smad7 e cadherin vimentin assessed 41 patients cca immunohistochemistry analyzed associations clinical parameters results smad7 vimentin expression cca tissue dramatically higher adjacent tissues addition smad7 vimentin e cadherin expression significantly associated cca lymph node metastasis perineural invasion p 0 05 factors gender age tumor location tumor type tumor differentiation degree p 0 05 overall survival relapse free survival rate significantly higher patients negative smad7 expression positive smad7 expression conclusion emt phenomena may occur process cca invasion metastasis smad7 highly expressed cca may considered one feedback regulator late stages potential prognostic indicator clinical assessment pubmed","probabilities":0.88235295,"Title":"Expression of Smad7 in cholangiocarcinoma: prognostic significance and implications for tumor metastasis","Abstract":"BACKGROUND: There are few molecular markers known to predict cholangiocarcinoma (CCA) prognosis. Smad7 has a certain relationship with epithelial-mesenchymal transition (EMT), but its relevance to CCA in unclear. Therefore expression and clinical significance of Smad7 in CCA was the focus of this study. METHODS: Expression of Smad7, E-cadherin and vimentin was assessed in 41 patients with CCA by immunohistochemistry and analyzed for associations with clinical parameters. RESULTS: Smad7 and vimentin expression in the CCA tissue was dramatically higher than that in adjacent tissues. In addition, Smad7, vimentin and E-cadherin expression was significantly associated with CCA lymph node metastasis and perineural invasion(P ≤ 0.05), but not other factors, such as gender, age, tumor location, tumor type and tumor differentiation degree (P>0.05). The overall survival and relapse-free survival rate was significantly higher in patients with negative Smad7 expression than those with positive Smad7 expression. CONCLUSION: EMT phenomena may occur in the process of CCA invasion and metastasis. Smad7, which was highly expressed in CCA, may be considered to be one feedback regulator in late stages and could have potential as a prognostic indicator for clinical assessment.","Source":"PubMed","category":"HUMAN","training_data":"Expression of Smad7 in cholangiocarcinoma: prognostic significance and implications for tumor metastasis BACKGROUND: There are few molecular markers known to predict cholangiocarcinoma (CCA) prognosis. Smad7 has a certain relationship with epithelial-mesenchymal transition (EMT), but its relevance to CCA in unclear. Therefore expression and clinical significance of Smad7 in CCA was the focus of this study. METHODS: Expression of Smad7, E-cadherin and vimentin was assessed in 41 patients with CCA by immunohistochemistry and analyzed for associations with clinical parameters. RESULTS: Smad7 and vimentin expression in the CCA tissue was dramatically higher than that in adjacent tissues. In addition, Smad7, vimentin and E-cadherin expression was significantly associated with CCA lymph node metastasis and perineural invasion(P ≤ 0.05), but not other factors, such as gender, age, tumor location, tumor type and tumor differentiation degree (P>0.05). The overall survival and relapse-free survival rate was significantly higher in patients with negative Smad7 expression than those with positive Smad7 expression. CONCLUSION: EMT phenomena may occur in the process of CCA invasion and metastasis. Smad7, which was highly expressed in CCA, may be considered to be one feedback regulator in late stages and could have potential as a prognostic indicator for clinical assessment. PubMed","prediction_labels":"HUMAN"},{"cleaned":"aggressive surgical treatment intrahepatic cholangiocarcinoma background intrahepatic cholangiocarcinoma icc second common primary liver cancer constitutes 10 primary liver malignancies surgery optimal therapy majority patients require extensive resections associated significant morbidity methods retrospectively studied records 26 patients underwent exploratory laparotomy intrahepatic cholangiocarcinoma june 1991 december 1997 mount sinai hospital patients perihilar klatskin tumors excluded patients considered resectable based ct mri findings patients positive margins nodal invasion received adjuvant chemotherapy radiation results sixteen patients underwent 18 resections 10 patients tumors unresectable laparotomy biopsy performed mean age 62 versus 53 years significantly higher mean total bilirubin level 0 71 versus 6 17 mg dl significantly lower resected group p 0 031 0 017 respectively patient total bilirubin 1 2 mg dl found resectable median actuarial survivals 42 9 8 9 months resectable 6 7 3 6 months unresectable patients p 0 005 positive margins associated significantly shorter disease free survival resected patients positive margins survived significantly longer unresectable tumor size presence satellite nodules degree tumor necrosis histologic examination significant predictors outcomes survival among patients receiving adjuvant therapy significantly altered conclusions conclude aggressive surgical approach warranted patients icc resection offers hope longterm survival findings emphasize importance achieving tumor free margins noncurative resection offers survival advantage resection histologic examination resected specimens help select patients poor prognoses google scholar","probabilities":0.9799733,"Title":"Aggressive Surgical Treatment Of Intrahepatic Cholangiocarcinoma","Abstract":"Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and constitutes 10% of primary liver malignancies. Surgery is the optimal therapy; the majority of the patients will require extensive resections that are associated with significant morbidity.\nMethods: We retrospectively studied the records of 26 patients who underwent exploratory laparotomy for intrahepatic cholangiocarcinoma between June 1991 and December 1997 at the Mount Sinai Hospital. Patients with perihilar (Klatskin) tumors were excluded. All patients were considered resectable based on CT or MRI findings. Patients with positive margins or nodal invasion received adjuvant chemotherapy and radiation.\nResults: Sixteen patients underwent 18 resections; in 10 patients the tumors were unresectable at laparotomy and only biopsy was performed. The mean age (62 versus 53 years) was significantly higher, and the mean total bilirubin level (0.71 versus 6.17 mg/dL) was significantly lower in the resected group (p = 0.031 and 0.017, respectively). No patient with a total bilirubin over 1.2 mg/dL was found to be resectable. Median actuarial survivals were 42.9 ± 8.9 months for resectable and 6.7 ± 3.6 months for unresectable patients (p = 0.005). Positive margins were associated with significantly shorter disease-free survival. But resected patients with positive margins survived significantly longer than those who were unresectable. Tumor size, presence of satellite nodules, and degree of tumor necrosis on histologic examination were significant predictors of outcomes. Survival among patients receiving adjuvant therapy was not significantly altered.\nConclusions: We conclude that an aggressive surgical approach is warranted in patients with ICC because resection offers the only hope for longterm survival. Our findings emphasize the importance of achieving tumor-free margins. Noncurative resection offers a survival advantage over no resection. Histologic examination of resected specimens can help select patients with poor prognoses.","Source":"Google Scholar","category":"HUMAN","training_data":"Aggressive Surgical Treatment Of Intrahepatic Cholangiocarcinoma Background: Intrahepatic cholangiocarcinoma (ICC) is the second most common primary liver cancer and constitutes 10% of primary liver malignancies. Surgery is the optimal therapy; the majority of the patients will require extensive resections that are associated with significant morbidity.\nMethods: We retrospectively studied the records of 26 patients who underwent exploratory laparotomy for intrahepatic cholangiocarcinoma between June 1991 and December 1997 at the Mount Sinai Hospital. Patients with perihilar (Klatskin) tumors were excluded. All patients were considered resectable based on CT or MRI findings. Patients with positive margins or nodal invasion received adjuvant chemotherapy and radiation.\nResults: Sixteen patients underwent 18 resections; in 10 patients the tumors were unresectable at laparotomy and only biopsy was performed. The mean age (62 versus 53 years) was significantly higher, and the mean total bilirubin level (0.71 versus 6.17 mg/dL) was significantly lower in the resected group (p = 0.031 and 0.017, respectively). No patient with a total bilirubin over 1.2 mg/dL was found to be resectable. Median actuarial survivals were 42.9 ± 8.9 months for resectable and 6.7 ± 3.6 months for unresectable patients (p = 0.005). Positive margins were associated with significantly shorter disease-free survival. But resected patients with positive margins survived significantly longer than those who were unresectable. Tumor size, presence of satellite nodules, and degree of tumor necrosis on histologic examination were significant predictors of outcomes. Survival among patients receiving adjuvant therapy was not significantly altered.\nConclusions: We conclude that an aggressive surgical approach is warranted in patients with ICC because resection offers the only hope for longterm survival. Our findings emphasize the importance of achieving tumor-free margins. Noncurative resection offers a survival advantage over no resection. Histologic examination of resected specimens can help select patients with poor prognoses. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"elevated ca 19 9 portends poor prognosis patients undergoing resection biliary malignancies background biliary tree malignancies including cholangiocarcinoma gallbladder cancer aggressive cancers high disease specific mortality despite resection aim present study identify predictors survival resection methods retrospective review patients underwent radical resection biliary malignancies performed demographics elevated ca19 9 35 u ml treatment outcome data collected compared according tumour location kaplan meier survival curves created compared using log rank analysis multivariate analysis undertaken using cox proportional hazards regression results ninety one patients biliary malignancies underwent surgical resection 1992 2007 46 50 5 extrahepatic cholangiocarcinomas ehc 23 25 2 intrahepatic cholangiocarcinomas ihc 22 24 2 gallbladder carcinomas gbc median range age 64 24 92 years elevated ca19 9 recorded 45 55 patients 52 ihc 63 ehc 41 gbc overall median range survival 22 5 0 3 153 3 months three groups similar terms age gender pre operative ca 19 9 level completeness resection tumour histopathological characteristics gbc associated shortest median survival 14 3 months followed ehc 24 8 months ihc 30 4 months however meet statistical significance p 0 971 elevated pre operative ca 19 9 level 35 u ml predictive poor median survival univariate p 0 003 multivariate analysis 15 1 months vs 67 4 p 0 047 conclusions elevated pre operative ca 19 9 levels found independent predictors poor survival attempted resection biliary tree malignancies recommended ca19 9 routinely measured prior resection stn","probabilities":0.9799733,"Title":"Elevated Ca 19-9 Portends Poor Prognosis In Patients Undergoing Resection Of Biliary Malignancies","Abstract":"Background: Biliary tree malignancies including cholangiocarcinoma and gallbladder cancer are aggressive cancers with a high disease-specific mortality despite resection. The aim of the present study was to identify predictors of survival after resection. \r\n\r\n Methods: A retrospective review of all patients that underwent radical resection of biliary malignancies was performed. Demographics, elevated CA19-9 (>35 U/ml), treatment and outcome data were collected and compared according to tumour location. Kaplan-Meier survival curves were created and compared using log-rank analysis. Multivariate analysis was undertaken using Cox proportional hazards regression. \r\n\r\n Results: Ninety-one patients with biliary malignancies underwent surgical resection between 1992 and 2007. There were 46 (50.5%) extrahepatic cholangiocarcinomas (EHC), 23 (25.2%) intrahepatic cholangiocarcinomas (IHC) and 22 (24.2%) gallbladder carcinomas (GBC). The median (range) age was 64 (24-92) years. An elevated CA19-9 was recorded in 45 (55%) patients (52% of IHC, 63% of EHC, and 41% of GBC). The overall median (range) survival was 22.5 (0.3-153.3) months. All three groups were similar in terms of age, gender, pre-operative CA 19-9 level, completeness of resection and tumour histopathological characteristics. GBC were associated with the shortest median survival (14.3 months) followed by EHC (24.8 months) and IHC (30.4 months); however, this did not meet statistical significance (P= 0.971). Only elevated pre-operative CA 19-9 level (>35 U/ml) was predictive of poor median survival by univariate (P= 0.003) and multivariate analysis (15.1 months vs. 67.4, P= 0.047). \r\n\r\n Conclusions: Elevated pre-operative CA 19-9 levels were found to be independent predictors of poor survival after attempted resection for biliary tree malignancies. It is recommended that CA19-9 be routinely measured prior resection.","Source":"STN","category":"HUMAN","training_data":"Elevated Ca 19-9 Portends Poor Prognosis In Patients Undergoing Resection Of Biliary Malignancies Background: Biliary tree malignancies including cholangiocarcinoma and gallbladder cancer are aggressive cancers with a high disease-specific mortality despite resection. The aim of the present study was to identify predictors of survival after resection. \r\n\r\n Methods: A retrospective review of all patients that underwent radical resection of biliary malignancies was performed. Demographics, elevated CA19-9 (>35 U/ml), treatment and outcome data were collected and compared according to tumour location. Kaplan-Meier survival curves were created and compared using log-rank analysis. Multivariate analysis was undertaken using Cox proportional hazards regression. \r\n\r\n Results: Ninety-one patients with biliary malignancies underwent surgical resection between 1992 and 2007. There were 46 (50.5%) extrahepatic cholangiocarcinomas (EHC), 23 (25.2%) intrahepatic cholangiocarcinomas (IHC) and 22 (24.2%) gallbladder carcinomas (GBC). The median (range) age was 64 (24-92) years. An elevated CA19-9 was recorded in 45 (55%) patients (52% of IHC, 63% of EHC, and 41% of GBC). The overall median (range) survival was 22.5 (0.3-153.3) months. All three groups were similar in terms of age, gender, pre-operative CA 19-9 level, completeness of resection and tumour histopathological characteristics. GBC were associated with the shortest median survival (14.3 months) followed by EHC (24.8 months) and IHC (30.4 months); however, this did not meet statistical significance (P= 0.971). Only elevated pre-operative CA 19-9 level (>35 U/ml) was predictive of poor median survival by univariate (P= 0.003) and multivariate analysis (15.1 months vs. 67.4, P= 0.047). \r\n\r\n Conclusions: Elevated pre-operative CA 19-9 levels were found to be independent predictors of poor survival after attempted resection for biliary tree malignancies. It is recommended that CA19-9 be routinely measured prior resection. STN","prediction_labels":"HUMAN"},{"cleaned":"impact perioperative ca19 9 change survival recurrence patterns adjuvant chemoradiotherapy resectable extrahepatic cholangiocarcinoma backgrounds perioperative ca19 9 value pancreato biliary cancers recognized prognostic factor herein investigated survival differences recurrence patterns adjuvant chemoradiotherapy perioperative ca19 9 change surgically resected extrahepatic cholangiocarcinoma methods patients divided preoperative normal ca19 9 group 1 n 52 high preoperative normalized postoperative ca19 9 group 2 n 80 high pre postoperative ca19 9 group 3 n 21 results depending group defined 5 year overall survival os 59 6 38 7 9 5 p 0 001 disease free survival 55 8 31 2 9 5 p 0 001 three groups differed multivariable analysis patients group 1 poor prognosticators os high postoperative ca19 9 hr 2 26 p 0 008 n1 disease hr 2 33 p 0 001 group 3 compared group 2 showed higher distant metastasis rate shorter disease free interval higher ca19 9 time recurrence conclusions survival recurrence patterns adjuvant chemoradiotherapy significantly affected perioperative ca19 9 change may important implications patient selection adjuvant chemoradiotherapy clinical trial design pubmed","probabilities":0.9799733,"Title":"The impact of perioperative CA19-9 change on the survival and recurrence patterns after adjuvant chemoradiotherapy in resectable extrahepatic cholangiocarcinoma","Abstract":"BACKGROUNDS: Perioperative CA19-9 value in pancreato-biliary cancers has been recognized as a prognostic factor. Herein, we investigated survival differences and recurrence patterns after adjuvant chemoradiotherapy by perioperative CA19-9 change in surgically resected extrahepatic cholangiocarcinoma. METHODS: Patients were divided into those with preoperative normal CA19-9 (Group 1, n = 52), those with high preoperative and normalized postoperative CA19-9 (Group 2, n = 80), and those with both high pre- and postoperative CA19-9 (Group 3, n = 21). RESULTS: Depending on the group defined above, the 5-year overall survival (OS) (59.6%, 38.7%, and 9.5%, P < 0.001) and disease-free survival (55.8%, 31.2%, and 9.5%, P < 0.001) between the three groups differed. On multivariable analysis in patients other than group 1, poor prognosticators for OS were high postoperative CA19-9 (HR 2.26, P = 0.008) and N1 disease (HR 2.33, P = 0.001). Group 3, compared with group 2, showed higher distant metastasis rate, shorter disease-free interval, and higher CA19-9 at the time of recurrence. CONCLUSIONS: Survival and recurrence patterns after adjuvant chemoradiotherapy are significantly affected by perioperative CA19-9 change. This may have important implications in patient selection for adjuvant chemoradiotherapy and clinical trial design.","Source":"PubMed","category":"HUMAN","training_data":"The impact of perioperative CA19-9 change on the survival and recurrence patterns after adjuvant chemoradiotherapy in resectable extrahepatic cholangiocarcinoma BACKGROUNDS: Perioperative CA19-9 value in pancreato-biliary cancers has been recognized as a prognostic factor. Herein, we investigated survival differences and recurrence patterns after adjuvant chemoradiotherapy by perioperative CA19-9 change in surgically resected extrahepatic cholangiocarcinoma. METHODS: Patients were divided into those with preoperative normal CA19-9 (Group 1, n = 52), those with high preoperative and normalized postoperative CA19-9 (Group 2, n = 80), and those with both high pre- and postoperative CA19-9 (Group 3, n = 21). RESULTS: Depending on the group defined above, the 5-year overall survival (OS) (59.6%, 38.7%, and 9.5%, P < 0.001) and disease-free survival (55.8%, 31.2%, and 9.5%, P < 0.001) between the three groups differed. On multivariable analysis in patients other than group 1, poor prognosticators for OS were high postoperative CA19-9 (HR 2.26, P = 0.008) and N1 disease (HR 2.33, P = 0.001). Group 3, compared with group 2, showed higher distant metastasis rate, shorter disease-free interval, and higher CA19-9 at the time of recurrence. CONCLUSIONS: Survival and recurrence patterns after adjuvant chemoradiotherapy are significantly affected by perioperative CA19-9 change. This may have important implications in patient selection for adjuvant chemoradiotherapy and clinical trial design. PubMed","prediction_labels":"HUMAN"},{"cleaned":"brd4 inhibitor histone deacetylase inhibitor synergistically inhibit proliferation gallbladder cancer vitro vivo gallbladder cancer gbc common malignancy bile duct high mortality rate demonstrated brd4 inhibitor jq1 histone deacetylase inhibitor suberoylanilide hydroxamic acid saha synergistically inhibited gbc cells vitro vivo results showed cotreatment jq1 saha significantly inhibited proliferation cell viability metastasis induced apoptosis g2 m arrest gbc cells minor effects benign cells vivo tumor volumes weights gbc xenograft models significantly decreased treatment jq1 saha meanwhile cotreatment showed strongest effect study indicated anticancer effects associated downregulation brd4 suppression pi3k akt mapk erk pathways findings highlight jq1 saha potential therapeutic agents combination promising therapeutic strategy gbc stn","probabilities":0.9467213,"Title":"Brd4 Inhibitor And Histone Deacetylase Inhibitor Synergistically Inhibit The Proliferation Of Gallbladder Cancer In Vitro And In Vivo","Abstract":"Gallbladder cancer (GBC) is the most common malignancy of the bile duct and has a high mortality rate. Here, we demonstrated that BRD4 inhibitor JQ1 and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) synergistically inhibited the GBC cells in vitro and in vivo. Our results showed that cotreatment with JQ1 and SAHA significantly inhibited proliferation, cell viability and metastasis, and induced apoptosis and G2/M arrest in GBC cells, with only minor effects in benign cells. In vivo, tumor volumes and weights of GBC xenograft models were significantly decreased after treatment with JQ1 or SAHA; meanwhile, the cotreatment showed the strongest effect. Further study indicated that the above anticancer effects was associated with the downregulation of BRD4 and suppression of PI3K/AKT and MAPK/ERK pathways. These findings highlight JQ1 and SAHA as potential therapeutic agents and their combination as a promising therapeutic strategy for GBC.","Source":"STN","category":"ANIMAL","training_data":"Brd4 Inhibitor And Histone Deacetylase Inhibitor Synergistically Inhibit The Proliferation Of Gallbladder Cancer In Vitro And In Vivo Gallbladder cancer (GBC) is the most common malignancy of the bile duct and has a high mortality rate. Here, we demonstrated that BRD4 inhibitor JQ1 and histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) synergistically inhibited the GBC cells in vitro and in vivo. Our results showed that cotreatment with JQ1 and SAHA significantly inhibited proliferation, cell viability and metastasis, and induced apoptosis and G2/M arrest in GBC cells, with only minor effects in benign cells. In vivo, tumor volumes and weights of GBC xenograft models were significantly decreased after treatment with JQ1 or SAHA; meanwhile, the cotreatment showed the strongest effect. Further study indicated that the above anticancer effects was associated with the downregulation of BRD4 and suppression of PI3K/AKT and MAPK/ERK pathways. These findings highlight JQ1 and SAHA as potential therapeutic agents and their combination as a promising therapeutic strategy for GBC. STN","prediction_labels":"ANIMAL"},{"cleaned":"gemcitabine plus cisplatin chemotherapy prolongs survival advanced hilar cholangiocarcinoma large multicenter study objectives gemcitabine plus cisplatin gc recommended first line treatment advanced cholangiocarcinoma investigated impact gc patients unresectable hilar cholangiocarcinoma hc based time taken effective biliary drainage ebd materials methods retrospectively enrolled 113 patients unresectable hc thirty nine 74 patients received gc chemotherapy best supportive care bsc respectively ebd defined reduction total bilirubin 50 value 2 mg dl drainage procedure early ebd eebd delayed ebd debd separated 2 weeks overall survival os estimated results gc group showed significantly longer median os bsc group 12 8 vs 6 1 mo p 0 001 moreover eebd group experienced significantly longer os debd group 8 2 vs 4 3 mo p 0 001 gc led improved os eebd 12 8 vs 6 8 mo p 0 003 debd 12 2 vs 3 4 mo p 0 009 groups multivariate analysis debd adjusted hazard ratio ahr 1 785 95 confidence interval ci 1 183 2 691 p 0 006 bsc ahr 2 409 95 ci 1 579 3 675 p 0 001 ecog status 2 ahr 3 721 95 ci 2 093 6 615 p 0 001 associated poor prognosis gc group older 70 y patients higher risk death younger patients conclusions gc prolongs survival patients unresectable hc even debd elderly stn","probabilities":0.9799733,"Title":"Gemcitabine Plus Cisplatin Chemotherapy Prolongs The Survival In Advanced Hilar Cholangiocarcinoma: A Large Multicenter Study","Abstract":"Objectives: Gemcitabine plus cisplatin (GC) is recommended as first-line treatment for advanced cholangiocarcinoma. We investigated the impact of GC in patients with unresectable hilar cholangiocarcinoma (HC) based on the time taken for effective biliary drainage (EBD). \r\n\r\n Materials and methods: We retrospectively enrolled 113 patients with unresectable HC. Thirty-nine and 74 patients received GC chemotherapy and best supportive care (BSC), respectively. EBD was defined as a reduction in total bilirubin >50% or to a value <2 mg/dL after the drainage procedure. Early EBD (eEBD) and delayed EBD (dEBD) were separated by 2 weeks. Overall survival (OS) was estimated. \r\n\r\n Results: The GC group showed a significantly longer median OS than the BSC group (12.8 vs. 6.1 mo; P<0.001). Moreover, the eEBD group experienced a significantly longer OS than the dEBD group (8.2 vs. 4.3 mo; P<0.001). GC led to improved OS in the eEBD (12.8 vs. 6.8 mo; P=0.003) and dEBD (12.2 vs. 3.4 mo; P=0.009) groups. In multivariate analysis, dEBD (adjusted hazard ratio [aHR], 1.785; 95% confidence interval [CI], 1.183-2.691; P=0.006), BSC (aHR, 2.409; 95% CI, 1.579-3.675; P<0.001), and an ECOG status ≥2 (aHR, 3.721; 95% CI, 2.093-6.615; P<0.001) were associated with poor prognosis. In GC group, the older (70 y and above) patients did not have a higher risk of death than younger patients. \r\n\r\n Conclusions: GC prolongs the survival of patients with unresectable HC, even those with dEBD or elderly.","Source":"STN","category":"HUMAN","training_data":"Gemcitabine Plus Cisplatin Chemotherapy Prolongs The Survival In Advanced Hilar Cholangiocarcinoma: A Large Multicenter Study Objectives: Gemcitabine plus cisplatin (GC) is recommended as first-line treatment for advanced cholangiocarcinoma. We investigated the impact of GC in patients with unresectable hilar cholangiocarcinoma (HC) based on the time taken for effective biliary drainage (EBD). \r\n\r\n Materials and methods: We retrospectively enrolled 113 patients with unresectable HC. Thirty-nine and 74 patients received GC chemotherapy and best supportive care (BSC), respectively. EBD was defined as a reduction in total bilirubin >50% or to a value <2 mg/dL after the drainage procedure. Early EBD (eEBD) and delayed EBD (dEBD) were separated by 2 weeks. Overall survival (OS) was estimated. \r\n\r\n Results: The GC group showed a significantly longer median OS than the BSC group (12.8 vs. 6.1 mo; P<0.001). Moreover, the eEBD group experienced a significantly longer OS than the dEBD group (8.2 vs. 4.3 mo; P<0.001). GC led to improved OS in the eEBD (12.8 vs. 6.8 mo; P=0.003) and dEBD (12.2 vs. 3.4 mo; P=0.009) groups. In multivariate analysis, dEBD (adjusted hazard ratio [aHR], 1.785; 95% confidence interval [CI], 1.183-2.691; P=0.006), BSC (aHR, 2.409; 95% CI, 1.579-3.675; P<0.001), and an ECOG status ≥2 (aHR, 3.721; 95% CI, 2.093-6.615; P<0.001) were associated with poor prognosis. In GC group, the older (70 y and above) patients did not have a higher risk of death than younger patients. \r\n\r\n Conclusions: GC prolongs the survival of patients with unresectable HC, even those with dEBD or elderly. STN","prediction_labels":"HUMAN"},{"cleaned":"relation gallbladder enlargement bile acid homeostasis colorectal malignancy primary sclerosing cholangitis background aim gallbladder enlargement frequent primary sclerosing cholangitis psc mice bile acid homeo stasis modified gallbladder shunt aim study assess potential cause influence gallbladder enlargement bile acid homeostasis disease course psc patients methods study population comprised 77 psc patients underwent three dimen sional magnetic resonance cholangiography 3d mrc mass spectrometry analysis serum bile acids within less month patients followed 9 5 years gallbladder volume calculated analysis 3d mrc images median value 69 ml taken cutoff separate patients two groups results gallbladder enlarged 35 patients 89 86 106 ml within normal range 42 41 35 47 ml patients enlarged gallbladders significantly differ others regarding gender 65 vs 66 males median age 43 vs 42 years time diagnosis 5 vs 5 5 years body mass index 21 6 vs 23 7 associated inflammatory bowel disease 71 vs 50 udca treatment 89 vs 90 mri features including cystic abnormali ties 8 5 vs 12 clinical histological parameters liver disease mayo risk score 0 18 0 45 0 27 vs 0 005 0 63 0 56 notably malignancy less frequent group enlarged gallbladder occurring 2 5 7 vs 11 26 2 patients normal gallbladder size p 0 029 colorectal cancer particular 6 7 fold less frequent occurring 1 2 8 vs 8 19 patients p 0 037 6 7 0 9 354 patients enlarged gallbladder serum concentrations secondary bile acids lower patients 1 6 1 3 1 9 vs 2 5 2 3 1 mol l p 0 0004 true deoxycholic acid 0 7 0 5 1 vs 2 2 1 6 3 mol l p 0 0001 secondary bile acid known promote colon carcinogenesis patients group also higher concentrations primary bile acids 10 5 6 6 16 7 vs 4 3 3 5 5 3 mol l p 0 0001 udca 44 0 29 4 52 vs 27 2 14 6 31 1 mol l p 0 001 furthermore higher serum concentrations gallbladder relaxing hormone fgf19 211 6 168 6 234 6 vs 88 6 72 7 121 6 pg ml p 0 0001 concentration correlated gallbladder volume r2 0 46 p 0 001 conclusion gallblad der enlarged approximately half psc patients caused increased fgf19 levels asso ciated lack secondary bile acids enhanced udca enrichment lower prevalence colorectal cancer con sistent protective properties gallbladder enlargement psc google scholar","probabilities":0.9799733,"Title":"Relation Of Gallbladder Enlargement With Bile Acid Homeostasis And Colorectal Malignancy In Primary Sclerosing Cholangitis","Abstract":"Background and aim: Gallbladder enlargement is frequent in primary sclerosing cholangitis (PSC). In mice, bile acid homeo-stasis can be modified by a gallbladder shunt. The aim of this study was to assess the potential cause and influence of gallbladder enlargement on bile acid homeostasis and disease course in PSC. Patients and methods: The study population comprised 77 PSC patients who underwent a three-dimen-sional magnetic resonance cholangiography (3D-MRC) and a mass spectrometry analysis of serum bile acids within less than a month. Patients were followed for 9±5 years. Gallbladder volume was calculated by the analysis of 3D-MRC images and the median value (69 mL) was taken as a cutoff to separate patients into two groups. Results: Gallbladder was enlarged in 35 patients (89 [86-106] mL) and within normal range in 42 (41 [35-47] mL). Patients with enlarged gallbladders did not significantly differ from others regarding gender (65% vs. 66% males), median age (43 vs. 42 years), time from diagnosis (5 vs. 5.5 years), body mass index (21.6 vs. 23.7), associated inflammatory bowel disease (71% vs. 50%), UDCA treatment (89% vs. 90%), other MRI features including cystic abnormali-ties (8.5% vs. 12%), clinical or histological parameters of liver disease (Mayo risk score of -0.18 [-0.45-0.27] vs. -0.005 [-0.63-0.56]). Notably, malignancy was less frequent in the group with enlarged gallbladder, occurring in 2 (5.7%) vs. 11 (26.2%) patients with normal gallbladder size (P=0.029). Colorectal cancer in particular was 6.7-fold less frequent, occurring in 1 (2.8%) vs. 8 (19%) patients (P=0.037, OR=6.7 [0.9- 354])). In patients with enlarged gallbladder, the serum concentrations of secondary bile acids were lower than in other patients (1.6 [1.3-1.9] vs. 2.5 [2-3.1] μmol/L, P=0.0004). This was true for deoxycholic acid (0.7 [0.5-1] vs. 2.2 [1-6-3] μmol/L, P=0.0001), a secondary bile acid known to promote colon carcinogenesis. Patients in this group also had higher concentrations of primary bile acids (10.5 [6.6-16.7] vs. 4.3 [3.5-5.3] μmol/L, P=0.0001) and of UDCA (44.0 [29.4-52] vs. 27.2 [14.6-31.1] μmol/L, P=0.001). Furthermore, they had higher serum concentrations of the gallbladder-relaxing hormone FGF19 (211.6 [168.6-234.6] vs. 88.6 [72.7-121.6] pg/mL, P=0.0001), which concentration was correlated with gallbladder volume (R2=0.46, P=0.001) Conclusion: Gallblad-der is enlarged in approximately half of PSC patients, which can be caused by increased FGF19 levels, and which is asso-ciated with a lack of secondary bile acids, enhanced UDCA enrichment and a lower prevalence of colorectal cancer, con-sistent with protective properties of gallbladder enlargement in PSC","Source":"Google Scholar","category":"HUMAN","training_data":"Relation Of Gallbladder Enlargement With Bile Acid Homeostasis And Colorectal Malignancy In Primary Sclerosing Cholangitis Background and aim: Gallbladder enlargement is frequent in primary sclerosing cholangitis (PSC). In mice, bile acid homeo-stasis can be modified by a gallbladder shunt. The aim of this study was to assess the potential cause and influence of gallbladder enlargement on bile acid homeostasis and disease course in PSC. Patients and methods: The study population comprised 77 PSC patients who underwent a three-dimen-sional magnetic resonance cholangiography (3D-MRC) and a mass spectrometry analysis of serum bile acids within less than a month. Patients were followed for 9±5 years. Gallbladder volume was calculated by the analysis of 3D-MRC images and the median value (69 mL) was taken as a cutoff to separate patients into two groups. Results: Gallbladder was enlarged in 35 patients (89 [86-106] mL) and within normal range in 42 (41 [35-47] mL). Patients with enlarged gallbladders did not significantly differ from others regarding gender (65% vs. 66% males), median age (43 vs. 42 years), time from diagnosis (5 vs. 5.5 years), body mass index (21.6 vs. 23.7), associated inflammatory bowel disease (71% vs. 50%), UDCA treatment (89% vs. 90%), other MRI features including cystic abnormali-ties (8.5% vs. 12%), clinical or histological parameters of liver disease (Mayo risk score of -0.18 [-0.45-0.27] vs. -0.005 [-0.63-0.56]). Notably, malignancy was less frequent in the group with enlarged gallbladder, occurring in 2 (5.7%) vs. 11 (26.2%) patients with normal gallbladder size (P=0.029). Colorectal cancer in particular was 6.7-fold less frequent, occurring in 1 (2.8%) vs. 8 (19%) patients (P=0.037, OR=6.7 [0.9- 354])). In patients with enlarged gallbladder, the serum concentrations of secondary bile acids were lower than in other patients (1.6 [1.3-1.9] vs. 2.5 [2-3.1] μmol/L, P=0.0004). This was true for deoxycholic acid (0.7 [0.5-1] vs. 2.2 [1-6-3] μmol/L, P=0.0001), a secondary bile acid known to promote colon carcinogenesis. Patients in this group also had higher concentrations of primary bile acids (10.5 [6.6-16.7] vs. 4.3 [3.5-5.3] μmol/L, P=0.0001) and of UDCA (44.0 [29.4-52] vs. 27.2 [14.6-31.1] μmol/L, P=0.001). Furthermore, they had higher serum concentrations of the gallbladder-relaxing hormone FGF19 (211.6 [168.6-234.6] vs. 88.6 [72.7-121.6] pg/mL, P=0.0001), which concentration was correlated with gallbladder volume (R2=0.46, P=0.001) Conclusion: Gallblad-der is enlarged in approximately half of PSC patients, which can be caused by increased FGF19 levels, and which is asso-ciated with a lack of secondary bile acids, enhanced UDCA enrichment and a lower prevalence of colorectal cancer, con-sistent with protective properties of gallbladder enlargement in PSC Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"elevated serum bilirubin level correlates development cholangiocarcinoma subsequent liver transplantation death patients primary sclerosing cholangitis introduction predicting clinical course primary sclerosing cholangitis psc difficult currently paucity studies evaluating serum chemistries predictors conventional clinical endpoints purpose study prognosticate key clinical endpoints patients psc elevated serum liver chemistries time initial presentation methods performed retrospective cohort study psc patients institution aim study determine association elevated liver chemistries initial presentation bilirubin alanine transaminase aspartate transaminase alkaline phosphatase primary outcome either cholangiocarcinoma liver transplantation death composite 3 secondary endpoints examined development severe biliary ductal disease need biliary stent placement results eighty one psc patients 61 males 20 females included study univariate analysis significant association initial bilirubin elevation 2x upper limit normal uln death p 0 009 multivariate regression analysis revealed elevated initial serum total bilirubin 2xuln p 0 017 significantly predicted composite endpoint univariate analysis pre endoscopic retrograde cholangiopancreatography labs serum bilirubin level elevation 2xuln showed association severity biliary ductal disease p 0 0001 logistic regression outcome variables also proved 2xuln serum bilirubin levels predicted ductal disease severity p 0 0001 conclusions initial elevation serum total bilirubin 2xuln psc patients correlates positively development cholangiocarcinoma subsequent liver transplantation death elevated bilirubin also correlates positively severity cholangiographic findings pubmed","probabilities":0.9799733,"Title":"Elevated Serum Bilirubin Level Correlates With the Development of Cholangiocarcinoma, Subsequent Liver Transplantation, and Death in Patients With Primary Sclerosing Cholangitis","Abstract":"INTRODUCTION: Predicting the clinical course of primary sclerosing cholangitis (PSC) is difficult. There are currently a paucity of studies evaluating serum chemistries as predictors of conventional clinical endpoints. The purpose of this study was to prognosticate key clinical endpoints in patients with PSC who had elevated serum liver chemistries at the time of their initial presentation. METHODS: We performed a retrospective cohort study of PSC patients at our institution. The aim of our study was to determine the association between elevated liver chemistries at initial presentation-bilirubin, alanine transaminase, aspartate transaminase, or alkaline phosphatase-with a primary outcome of either cholangiocarcinoma, liver transplantation, death, or composite of the 3. The secondary endpoints examined were development of severe biliary ductal disease and need for biliary stent placement. RESULTS: Eighty-one PSC patients (61 males and 20 females) were included in this study. By univariate analysis, there was a significant association between initial bilirubin elevation >2x the upper limit of normal (ULN) and death (P<0.009). Multivariate regression analysis revealed that an elevated initial serum total bilirubin >2xULN (P<0.017) significantly predicted the composite endpoint. By univariate analysis of pre-endoscopic retrograde cholangiopancreatography labs, serum bilirubin level elevation >2xULN showed an association with severity of biliary ductal disease (P<0.0001). A logistic regression of outcome variables also proved that >2xULN serum bilirubin levels predicted the ductal disease severity (P<0.0001). CONCLUSIONS: An initial elevation of serum total bilirubin >2xULN in PSC patients correlates positively with the development of cholangiocarcinoma, subsequent liver transplantation, and death. Elevated bilirubin also correlates positively with the severity of cholangiographic findings.","Source":"PubMed","category":"HUMAN","training_data":"Elevated Serum Bilirubin Level Correlates With the Development of Cholangiocarcinoma, Subsequent Liver Transplantation, and Death in Patients With Primary Sclerosing Cholangitis INTRODUCTION: Predicting the clinical course of primary sclerosing cholangitis (PSC) is difficult. There are currently a paucity of studies evaluating serum chemistries as predictors of conventional clinical endpoints. The purpose of this study was to prognosticate key clinical endpoints in patients with PSC who had elevated serum liver chemistries at the time of their initial presentation. METHODS: We performed a retrospective cohort study of PSC patients at our institution. The aim of our study was to determine the association between elevated liver chemistries at initial presentation-bilirubin, alanine transaminase, aspartate transaminase, or alkaline phosphatase-with a primary outcome of either cholangiocarcinoma, liver transplantation, death, or composite of the 3. The secondary endpoints examined were development of severe biliary ductal disease and need for biliary stent placement. RESULTS: Eighty-one PSC patients (61 males and 20 females) were included in this study. By univariate analysis, there was a significant association between initial bilirubin elevation >2x the upper limit of normal (ULN) and death (P<0.009). Multivariate regression analysis revealed that an elevated initial serum total bilirubin >2xULN (P<0.017) significantly predicted the composite endpoint. By univariate analysis of pre-endoscopic retrograde cholangiopancreatography labs, serum bilirubin level elevation >2xULN showed an association with severity of biliary ductal disease (P<0.0001). A logistic regression of outcome variables also proved that >2xULN serum bilirubin levels predicted the ductal disease severity (P<0.0001). CONCLUSIONS: An initial elevation of serum total bilirubin >2xULN in PSC patients correlates positively with the development of cholangiocarcinoma, subsequent liver transplantation, and death. Elevated bilirubin also correlates positively with the severity of cholangiographic findings. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival improvement prognostic factors recent management extrahepatic cholangiocarcinoma single center study background cholangiocarcinoma considered dismal disease poor prognosis recently cholangiocarcinoma increasingly found due increased life expectancy although surgical medical management advanced recently data prognosis especially extrahepatic cholangiocarcinoma ecc limited study aimed identify clinicopathologic features prognosis patients ecc methods patients followed diagnosed ecc january 2014 december 2016 tertiary hospital included whereas intrahepatic cholangiocarcinoma gallbladder cancer ampullary cancer excluded results total 83 patients followed treatment 49 men 34 women median age 73 3 years cancer location classified distal common bile duct 25 patients proximal common bile duct 24 patients common hepatic duct 20 patients hilar 14 patients 14 5 patients history another malignant neoplasm 24 1 patients chronic illness surgical resection performed 54 patients 65 dysplasia combined 63 34 54 adjuvant chemotherapy performed 54 29 54 7 underwent palliative chemotherapy 29 nonsurgical patients median overall survival patients 30 9 months analyzing treatment modality median survival adjuvant chemotherapy surgery palliative chemotherapy supportive care groups 42 9 30 9 12 0 8 9 months respectively p 0 05 cox regression analysis survival age surgical resection chemotherapy comorbidity significant prognostic factors comorbidity significant prognostic factor multivariable analysis hazard ratio hr 2 80 95 ci 1 32 5 95 p 0 007 subgroup analysis surgical patients presence dysplasia favorable prognostic factor multivariable analysis hr 0 29 95 ci 0 09 0 91 p 0 033 conclusions overall survival patients ecc quite high increased chemotherapy absence comorbidity presence dysplasia good prognostic factors stn","probabilities":0.9799733,"Title":"Survival Improvement And Prognostic Factors In Recent Management Of Extrahepatic Cholangiocarcinoma: A Single-Center Study","Abstract":"Background: Cholangiocarcinoma was considered as a dismal disease with very poor prognosis until recently. Cholangiocarcinoma is increasingly found due to increased life expectancy. Although surgical and medical management were advanced recently, data on the prognosis, especially extrahepatic cholangiocarcinoma (ECC), were limited. This study aimed to identify clinicopathologic features and prognosis of patients with ECC. \n\n Methods: Patients followed up and diagnosed with ECC between January 2014 and December 2016 at a tertiary hospital were included, whereas those with intrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer were excluded. \n\n Results: A total of 83 patients were followed after the treatment (49 men and 34 women; median age 73.3 years). Cancer location was classified as distal common bile duct (25 patients), proximal common bile duct (24 patients), common hepatic duct (20 patients), and hilar (14 patients). About 14.5% of patients had history of another malignant neoplasm, and 24.1% patients had chronic illness. Surgical resection was performed in 54 patients (65%) and dysplasia was combined in 63% (34/54). Adjuvant chemotherapy was performed in 54% (29/54), but only 7 underwent palliative chemotherapy in 29 nonsurgical patients. The median overall survival in all patients was 30.9 months. In analyzing the treatment modality, median survival of adjuvant chemotherapy, surgery only, palliative chemotherapy, and supportive care groups were 42.9, 30.9, 12.0, and 8.9 months, respectively (P < 0.05). In the Cox regression analysis of survival, age, surgical resection, chemotherapy, and comorbidity were significant prognostic factors, and the comorbidity was the only significant prognostic factor in the multivariable analysis (hazard ratio [HR] = 2.80; 95% CI: 1.32-5.95; P = 0.007). In a subgroup analysis of surgical patients, the presence of dysplasia was a favorable prognostic factor in the multivariable analysis (HR = 0.29; 95% CI: 0.09-0.91; P = 0.033). \n\n Conclusions: The overall survival of patients with ECC was quite high and increased with chemotherapy. Absence of comorbidity, and presence of dysplasia were good prognostic factors.","Source":"STN","category":"HUMAN","training_data":"Survival Improvement And Prognostic Factors In Recent Management Of Extrahepatic Cholangiocarcinoma: A Single-Center Study Background: Cholangiocarcinoma was considered as a dismal disease with very poor prognosis until recently. Cholangiocarcinoma is increasingly found due to increased life expectancy. Although surgical and medical management were advanced recently, data on the prognosis, especially extrahepatic cholangiocarcinoma (ECC), were limited. This study aimed to identify clinicopathologic features and prognosis of patients with ECC. \n\n Methods: Patients followed up and diagnosed with ECC between January 2014 and December 2016 at a tertiary hospital were included, whereas those with intrahepatic cholangiocarcinoma, gallbladder cancer, and ampullary cancer were excluded. \n\n Results: A total of 83 patients were followed after the treatment (49 men and 34 women; median age 73.3 years). Cancer location was classified as distal common bile duct (25 patients), proximal common bile duct (24 patients), common hepatic duct (20 patients), and hilar (14 patients). About 14.5% of patients had history of another malignant neoplasm, and 24.1% patients had chronic illness. Surgical resection was performed in 54 patients (65%) and dysplasia was combined in 63% (34/54). Adjuvant chemotherapy was performed in 54% (29/54), but only 7 underwent palliative chemotherapy in 29 nonsurgical patients. The median overall survival in all patients was 30.9 months. In analyzing the treatment modality, median survival of adjuvant chemotherapy, surgery only, palliative chemotherapy, and supportive care groups were 42.9, 30.9, 12.0, and 8.9 months, respectively (P < 0.05). In the Cox regression analysis of survival, age, surgical resection, chemotherapy, and comorbidity were significant prognostic factors, and the comorbidity was the only significant prognostic factor in the multivariable analysis (hazard ratio [HR] = 2.80; 95% CI: 1.32-5.95; P = 0.007). In a subgroup analysis of surgical patients, the presence of dysplasia was a favorable prognostic factor in the multivariable analysis (HR = 0.29; 95% CI: 0.09-0.91; P = 0.033). \n\n Conclusions: The overall survival of patients with ECC was quite high and increased with chemotherapy. Absence of comorbidity, and presence of dysplasia were good prognostic factors. STN","prediction_labels":"HUMAN"},{"cleaned":"individualized metabolic profiling stratifies pancreatic biliary tract cancer useful tool innovative screening programs predictive strategies healthcare background pancreatic cancer pc biliary tract cancer btc highly aggressive cancers characterized rarity difficulty diagnosis overall poor prognosis diagnosis pc btc complex made using combination appropriate clinical suspicion imaging endoscopic techniques cytopathological examination however late stage detection poor prognosis tumor led urgent need biomarkers early predictive diagnosis improved personalized treatments working hypothesis two hypotheses focusing low mass metabolites blood first valuable information obtained masses relative amounts metabolites present low mass ions lmis mass spectra second metabolic profiling individuals may provide important information regarding biological changes disease states useful early diagnosis pc btc materials methods assess whether profiling metabolites serum serve non invasive screening tool pc btc 320 serum samples obtained patients pc n 51 btc n 39 colorectal cancer crc n 100 ovarian cancer ovc n 30 healthy control subjects control n 100 obtained information relative amounts metabolites lmis via triple time flight mass spectrometry data analyzed according peak area ratios discriminative lmis results conclusions levels 14 discriminative lmis higher pc btc groups control crc ovc groups two lmis discriminated pc btc lysophosphatidylcholine lysopc 16 0 lysopc 20 4 levels two lysopcs also slightly lower pc btc crc ovc groups compared control group taken together data showed metabolic profiling precisely denote status cancer thus useful screening study details efficient methods identify discriminative lmis cancer screening also provides example metabolic profiling distinguishing pc btc furthermore two metabolites lysopc 16 0 lysopc 20 4 shown discriminate diseases potentially useful combined previously identified protein metabolic biomarkers predictive preventive personalized medical approach google scholar","probabilities":0.9799733,"Title":"Individualized Metabolic Profiling Stratifies Pancreatic And Biliary Tract Cancer: A Useful Tool For Innovative Screening Programs And Predictive Strategies In Healthcare","Abstract":"Background\nPancreatic cancer (PC) and biliary tract cancer (BTC) are highly aggressive cancers, characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. Diagnosis of PC and BTC is complex and is made using a combination of appropriate clinical suspicion, imaging and endoscopic techniques, and cytopathological examination. However, the late-stage detection and poor prognosis of this tumor have led to an urgent need for biomarkers for early and/or predictive diagnosis and improved personalized treatments.\nWorking hypothesis\nThere are two hypotheses for focusing on low-mass metabolites in the blood. First, valuable information can be obtained from the masses and relative amounts of such metabolites, which present as low-mass ions (LMIs) in mass spectra. Second, metabolic profiling of individuals may provide important information regarding biological changes in disease states that is useful for the early diagnosis of PC and BTC.\nMaterials and methods\nTo assess whether profiling metabolites in serum can serve as a non-invasive screening tool for PC and BTC, 320 serum samples were obtained from patients with PC (n = 51), BTC (n = 39), colorectal cancer (CRC) (n = 100), and ovarian cancer (OVC) (n = 30), and from healthy control subjects (control) (n = 100). We obtained information on the relative amounts of metabolites, as LMIs, via triple time-of-flight mass spectrometry. All data were analyzed according to the peak area ratios of discriminative LMIs.\nResults and conclusions\nThe levels of the 14 discriminative LMIs were higher in the PC and BTC groups than in the control, CRC and OVC groups, but only two LMIs discriminated between PC and BTC: lysophosphatidylcholine (LysoPC) (16:0) and LysoPC(20:4). The levels of these two LysoPCs were also slightly lower in the PC/BTC/CRC/OVC groups compared with the control group. Taken together, the data showed that metabolic profiling can precisely denote the status of cancer, and, thus, could be useful for screening. This study not only details efficient methods to identify discriminative LMIs for cancer screening but also provides an example of metabolic profiling for distinguishing PC from BTC. Furthermore, the two metabolites [LysoPC(16:0), LysoPC(20:4)] shown to discriminate these diseases are potentially useful when combined with other, previously identified protein or metabolic biomarkers for predictive, preventive and personalized medical approach.","Source":"Google Scholar","category":"HUMAN","training_data":"Individualized Metabolic Profiling Stratifies Pancreatic And Biliary Tract Cancer: A Useful Tool For Innovative Screening Programs And Predictive Strategies In Healthcare Background\nPancreatic cancer (PC) and biliary tract cancer (BTC) are highly aggressive cancers, characterized by their rarity, difficulty in diagnosis, and overall poor prognosis. Diagnosis of PC and BTC is complex and is made using a combination of appropriate clinical suspicion, imaging and endoscopic techniques, and cytopathological examination. However, the late-stage detection and poor prognosis of this tumor have led to an urgent need for biomarkers for early and/or predictive diagnosis and improved personalized treatments.\nWorking hypothesis\nThere are two hypotheses for focusing on low-mass metabolites in the blood. First, valuable information can be obtained from the masses and relative amounts of such metabolites, which present as low-mass ions (LMIs) in mass spectra. Second, metabolic profiling of individuals may provide important information regarding biological changes in disease states that is useful for the early diagnosis of PC and BTC.\nMaterials and methods\nTo assess whether profiling metabolites in serum can serve as a non-invasive screening tool for PC and BTC, 320 serum samples were obtained from patients with PC (n = 51), BTC (n = 39), colorectal cancer (CRC) (n = 100), and ovarian cancer (OVC) (n = 30), and from healthy control subjects (control) (n = 100). We obtained information on the relative amounts of metabolites, as LMIs, via triple time-of-flight mass spectrometry. All data were analyzed according to the peak area ratios of discriminative LMIs.\nResults and conclusions\nThe levels of the 14 discriminative LMIs were higher in the PC and BTC groups than in the control, CRC and OVC groups, but only two LMIs discriminated between PC and BTC: lysophosphatidylcholine (LysoPC) (16:0) and LysoPC(20:4). The levels of these two LysoPCs were also slightly lower in the PC/BTC/CRC/OVC groups compared with the control group. Taken together, the data showed that metabolic profiling can precisely denote the status of cancer, and, thus, could be useful for screening. This study not only details efficient methods to identify discriminative LMIs for cancer screening but also provides an example of metabolic profiling for distinguishing PC from BTC. Furthermore, the two metabolites [LysoPC(16:0), LysoPC(20:4)] shown to discriminate these diseases are potentially useful when combined with other, previously identified protein or metabolic biomarkers for predictive, preventive and personalized medical approach. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"association cholecystectomy intestinal cancer national record linkage study objective investigate risk intestinal cancer cohort people undergone cholecystectomy gallstones cohort people hospitalized gallbladder disease undergone cholecystectomy background investigators suggested cholecystectomy increases risk intestinal cancer despite extensive study evidence remains inconclusive doubt safety question arises whether patients considering operation told possible risk also increasingly clear noncausal associations gallstones intestinal cancer method analysis record linked hospital admission mortality statistics england 1998 2008 calculation ratio rates cancers cholecystectomy cohort gallbladder disease cohort compared control cohort results first year cholecystectomy rate ratios cancer small intestine colon rectum significantly high respectively 4 6 95 confidence interval 3 9 5 5 2 0 1 9 2 1 1 7 1 6 1 9 rates cancers also significantly high people gallstones without cholecystectomy 8 10 years cholecystectomy rate ratios declined nonsignificant levels conclusions cancers associated gallstones highest elevation risk cancer cholecystectomy shortest time interval operation thereafter level risk cholecystectomy control cohorts gradually converged association study cholecystectomy intestinal cancer unlikely causal intestinal cancers occasion initially misdiagnosed gallbladder disease pubmed","probabilities":0.9799733,"Title":"Association between cholecystectomy and intestinal cancer: a national record linkage study","Abstract":"OBJECTIVE: To investigate the risk of intestinal cancer in a cohort of people who had undergone cholecystectomy for gallstones, and in a cohort of people who had been hospitalized for gallbladder disease but had not undergone cholecystectomy. BACKGROUND: Some investigators have suggested that cholecystectomy increases the risk of intestinal cancer. Despite extensive study, the evidence remains inconclusive. If there is doubt about safety, the question arises of whether patients considering the operation should be told of a possible risk. It is also increasingly clear that there are noncausal associations between gallstones and intestinal cancer. METHOD: Analysis of record-linked hospital admission and mortality statistics for England from 1998 to 2008; calculation of ratio of rates of cancers in the cholecystectomy cohort and the gallbladder disease cohort compared with a control cohort. RESULTS: : In the first year after cholecystectomy, the rate ratios for cancer of the small intestine, colon, and rectum were significantly high at, respectively, 4.6 (95% confidence interval 3.9-5.5), 2.0 (1.9-2.1), and 1.7 (1.6-1.9). Rates of these cancers were also significantly high in people with gallstones without cholecystectomy. By 8 to 10 years after cholecystectomy, rate ratios had declined to nonsignificant levels. CONCLUSIONS: These cancers are associated with gallstones. The highest elevation of risk of cancer after cholecystectomy was at the shortest time interval after operation. Thereafter, the level of risk in the cholecystectomy and control cohorts gradually converged. The association in this study, between cholecystectomy and intestinal cancer, is very unlikely to be causal. Intestinal cancers are, on occasion, initially misdiagnosed as gallbladder disease.","Source":"PubMed","category":"HUMAN","training_data":"Association between cholecystectomy and intestinal cancer: a national record linkage study OBJECTIVE: To investigate the risk of intestinal cancer in a cohort of people who had undergone cholecystectomy for gallstones, and in a cohort of people who had been hospitalized for gallbladder disease but had not undergone cholecystectomy. BACKGROUND: Some investigators have suggested that cholecystectomy increases the risk of intestinal cancer. Despite extensive study, the evidence remains inconclusive. If there is doubt about safety, the question arises of whether patients considering the operation should be told of a possible risk. It is also increasingly clear that there are noncausal associations between gallstones and intestinal cancer. METHOD: Analysis of record-linked hospital admission and mortality statistics for England from 1998 to 2008; calculation of ratio of rates of cancers in the cholecystectomy cohort and the gallbladder disease cohort compared with a control cohort. RESULTS: : In the first year after cholecystectomy, the rate ratios for cancer of the small intestine, colon, and rectum were significantly high at, respectively, 4.6 (95% confidence interval 3.9-5.5), 2.0 (1.9-2.1), and 1.7 (1.6-1.9). Rates of these cancers were also significantly high in people with gallstones without cholecystectomy. By 8 to 10 years after cholecystectomy, rate ratios had declined to nonsignificant levels. CONCLUSIONS: These cancers are associated with gallstones. The highest elevation of risk of cancer after cholecystectomy was at the shortest time interval after operation. Thereafter, the level of risk in the cholecystectomy and control cohorts gradually converged. The association in this study, between cholecystectomy and intestinal cancer, is very unlikely to be causal. Intestinal cancers are, on occasion, initially misdiagnosed as gallbladder disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pretreatment body mass index weight change initial period chemotherapy affect survival outcome advanced biliary tract cancer patients background impact obesity survival known vary different cancers advanced biliary tract cancer rarely analyzed relationship obesity prognosis performed study evaluate bmi body weight change prognostic factors advanced biliary tract cancer patients palliative chemotherapy methods january 2005 december 2016 two hundred seventy six patients underwent chemotherapy biliary tract cancer retrospectively analyzed relationship bmi kg m2 clinical outcomes including overall progression free survival assessed additionally relationship change body composition overall survival evaluated results median overall survival 9 7 months underweight patients 10 1 months normal patients 15 8 months overweight group 13 1 months obese patients respectively p 0 047 univariate analysis showed bmi stage iii age less 64 year old gallbladder cancer operation radiotherapy ecog performance significantly associated better survival compared normal patients overweight patients bmi 23 24 9kg m2 reduced risk mortality multivariate analysis hr 0 632 95 ci 0 436 0 918 p 0 016 additional analysis effect changes body weight bmi overall survival decrease body weight bmi hr 1 410 95 ci 1 168 1 986 p 0 046 associated shorter overall survival conclusion overweight status maintenance body weight initial period chemotherapy important independent predictors better overall survival advanced biliary tract cancer patients stn","probabilities":0.9799733,"Title":"Pretreatment Body Mass Index And Weight Change During Initial Period Of Chemotherapy Affect Survival Outcome In Advanced Biliary Tract Cancer Patients","Abstract":"Background: The impact of obesity on survival is known to vary in different cancers. Advanced biliary tract cancer was rarely analyzed about the relationship between obesity and prognosis. We performed this study to evaluate the BMI and body weight change as prognostic factors for advanced biliary tract cancer patients with palliative chemotherapy. \r\n\r\n Methods: Between January 2005 and December 2016, two hundred and seventy-six patients who underwent chemotherapy for biliary tract cancer were retrospectively analyzed. The relationship between BMI (kg/m2) and clinical outcomes including overall and progression-free survival was assessed. Additionally the relationship between change in body composition and overall survival was evaluated. \r\n\r\n Results: Median overall survival was 9.7 months for underweight patients, 10.1 months for normal patients, 15.8 months for overweight group, 13.1 months for obese patients, respectively. (p = 0.047) Univariate analysis showed that BMI, stage III, age less than 64 year-old, gallbladder cancer, operation, radiotherapy and ECOG performance were significantly associated with better survival. Compared with normal patients, overweight patients (BMI 23-24.9kg/m2) had a reduced risk of mortality in multivariate analysis (HR 0.632; 95% CI 0.436-0.918, p = 0.016). In the additional analysis for the effect of changes in body weight and BMI to the overall survival, decrease in body weight and BMI (HR 1.410, 95% CI 1.168-1.986, p = 0.046) was associated with a shorter in overall survival. \r\n\r\n Conclusion: Overweight status and the maintenance of body weight during the initial period of chemotherapy are important and independent predictors of better overall survival in advanced biliary tract cancer patients.","Source":"STN","category":"HUMAN","training_data":"Pretreatment Body Mass Index And Weight Change During Initial Period Of Chemotherapy Affect Survival Outcome In Advanced Biliary Tract Cancer Patients Background: The impact of obesity on survival is known to vary in different cancers. Advanced biliary tract cancer was rarely analyzed about the relationship between obesity and prognosis. We performed this study to evaluate the BMI and body weight change as prognostic factors for advanced biliary tract cancer patients with palliative chemotherapy. \r\n\r\n Methods: Between January 2005 and December 2016, two hundred and seventy-six patients who underwent chemotherapy for biliary tract cancer were retrospectively analyzed. The relationship between BMI (kg/m2) and clinical outcomes including overall and progression-free survival was assessed. Additionally the relationship between change in body composition and overall survival was evaluated. \r\n\r\n Results: Median overall survival was 9.7 months for underweight patients, 10.1 months for normal patients, 15.8 months for overweight group, 13.1 months for obese patients, respectively. (p = 0.047) Univariate analysis showed that BMI, stage III, age less than 64 year-old, gallbladder cancer, operation, radiotherapy and ECOG performance were significantly associated with better survival. Compared with normal patients, overweight patients (BMI 23-24.9kg/m2) had a reduced risk of mortality in multivariate analysis (HR 0.632; 95% CI 0.436-0.918, p = 0.016). In the additional analysis for the effect of changes in body weight and BMI to the overall survival, decrease in body weight and BMI (HR 1.410, 95% CI 1.168-1.986, p = 0.046) was associated with a shorter in overall survival. \r\n\r\n Conclusion: Overweight status and the maintenance of body weight during the initial period of chemotherapy are important and independent predictors of better overall survival in advanced biliary tract cancer patients. STN","prediction_labels":"HUMAN"},{"cleaned":"extranodal extension n1 adenocarcinoma pancreas papilla vater systematic review meta analysis prognostic significance aim study investigate prognostic role extranodal extension ene lymph node metastasis adenocarcinoma pancreas pdac papilla cancer papilla vater cpv pubmed scopus search database inception 5 january 2015 without language restrictions conducted eligible prospective studies reporting data prognostic parameters individuals pdac cpv comparing participants presence ene ene intranodal extension ene data summarized using risk ratios number deaths recurrences hazard ratios time dependent risk related ene adjusted potential confounders ene found common tumors 60 n1 pdac cpv leading significant increased risk cause mortality risk ratio 1 20 95 confidence interval ci 1 06 1 35 p 0 003 2 44 hazard ratio 1 415 95 ci 1 215 1 650 p 0 0001 2 0 recurrence disease risk ratio 1 20 95 ci 1 03 1 40 p 0 02 2 0 basis results pdac cpv ene considered mandatorily gross sampling pathology report oncologic staging therapeutic approach pubmed","probabilities":0.9799733,"Title":"Extranodal extension in N1-adenocarcinoma of the pancreas and papilla of Vater: a systematic review and meta-analysis of its prognostic significance","Abstract":"The aim of the study was to investigate the prognostic role of extranodal extension (ENE) of lymph node metastasis in adenocarcinoma of the pancreas (PDAC) and papilla [cancer of the papilla of Vater (CPV)]. A PubMed and SCOPUS search from database inception until 5 January 2015 without language restrictions was conducted. Eligible were prospective studies reporting data on prognostic parameters in individuals with PDAC and/or CPV, comparing participants with the presence of ENE (ENE+) with those with intranodal extension (ENE-). Data were summarized using risk ratios for number of deaths/recurrences and hazard ratios for time-dependent risk related to ENE+, adjusted for potential confounders. ENE was found to be very common in these tumors (up to about 60% in both N1-PDAC and CPV), leading to a significant increased risk for all-cause mortality [risk ratio=1.20; 95% confidence interval (CI): 1.06-1.35, P=0.003, I(2)=44%; hazard ratio=1.415, 95% CI: 1.215-1.650, P<0.0001, I(2)=0%] and recurrence of disease (risk ratio=1.20, 95% CI: 1.03-1.40, P=0.02, I(2)=0%). On the basis of our results, in PDAC and CPV, ENE should be considered mandatorily from the gross sampling and pathology report to the oncologic staging and therapeutic approach.","Source":"PubMed","category":"HUMAN","training_data":"Extranodal extension in N1-adenocarcinoma of the pancreas and papilla of Vater: a systematic review and meta-analysis of its prognostic significance The aim of the study was to investigate the prognostic role of extranodal extension (ENE) of lymph node metastasis in adenocarcinoma of the pancreas (PDAC) and papilla [cancer of the papilla of Vater (CPV)]. A PubMed and SCOPUS search from database inception until 5 January 2015 without language restrictions was conducted. Eligible were prospective studies reporting data on prognostic parameters in individuals with PDAC and/or CPV, comparing participants with the presence of ENE (ENE+) with those with intranodal extension (ENE-). Data were summarized using risk ratios for number of deaths/recurrences and hazard ratios for time-dependent risk related to ENE+, adjusted for potential confounders. ENE was found to be very common in these tumors (up to about 60% in both N1-PDAC and CPV), leading to a significant increased risk for all-cause mortality [risk ratio=1.20; 95% confidence interval (CI): 1.06-1.35, P=0.003, I(2)=44%; hazard ratio=1.415, 95% CI: 1.215-1.650, P<0.0001, I(2)=0%] and recurrence of disease (risk ratio=1.20, 95% CI: 1.03-1.40, P=0.02, I(2)=0%). On the basis of our results, in PDAC and CPV, ENE should be considered mandatorily from the gross sampling and pathology report to the oncologic staging and therapeutic approach. PubMed","prediction_labels":"HUMAN"},{"cleaned":"primary sclerosing cholangitis malignancy cholangiocarcinoma complicates primary sclerosing cholangitis psc approximately 10 cases risk factor identify subgroup patients known imaging modalities serum tumour markers diagnose early cholangiocarcinoma available endoscopic retrograde cholangiography brush cytology recommended clinically indicated liver transplantation neoadjuvant therapy carried specialist centres cases limited stage cancer transplantation also considered patients biliary dysplasia without evident tumour gallbladder polyps psc often malignant liberal indication cholecystectomy recommended hepatocellular carcinoma develops 2 4 patients end stage liver disease patients inflammatory bowel disease risk colorectal neoplasia surveillance colonoscopies recommended also liver transplantation epigenetic markers represent one among several classes potential biomarkers early diagnosis malignancies psc explored pubmed","probabilities":0.9799733,"Title":"Primary sclerosing cholangitis and malignancy","Abstract":"Cholangiocarcinoma complicates primary sclerosing cholangitis (PSC) in approximately 10% of cases, but no risk factor that can identify this subgroup of patients is known. No imaging modalities or serum tumour markers that can diagnose early cholangiocarcinoma are available, but endoscopic retrograde cholangiography with brush cytology is recommended when clinically indicated. Liver transplantation with neoadjuvant therapy is carried out in specialist centres in cases of limited stage cancer. Transplantation should also be considered in patients with biliary dysplasia without evident tumour. Gallbladder polyps in PSC are often malignant, and liberal indication for cholecystectomy is recommended. Hepatocellular carcinoma develops in 2%-4% of patients with end-stage liver disease. Patients with inflammatory bowel disease are at risk of colorectal neoplasia. Surveillance colonoscopies are recommended, also after liver transplantation. Epigenetic markers represent one among several classes of potential biomarkers for early diagnosis of malignancies in PSC that should be further explored.","Source":"PubMed","category":"HUMAN","training_data":"Primary sclerosing cholangitis and malignancy Cholangiocarcinoma complicates primary sclerosing cholangitis (PSC) in approximately 10% of cases, but no risk factor that can identify this subgroup of patients is known. No imaging modalities or serum tumour markers that can diagnose early cholangiocarcinoma are available, but endoscopic retrograde cholangiography with brush cytology is recommended when clinically indicated. Liver transplantation with neoadjuvant therapy is carried out in specialist centres in cases of limited stage cancer. Transplantation should also be considered in patients with biliary dysplasia without evident tumour. Gallbladder polyps in PSC are often malignant, and liberal indication for cholecystectomy is recommended. Hepatocellular carcinoma develops in 2%-4% of patients with end-stage liver disease. Patients with inflammatory bowel disease are at risk of colorectal neoplasia. Surveillance colonoscopies are recommended, also after liver transplantation. Epigenetic markers represent one among several classes of potential biomarkers for early diagnosis of malignancies in PSC that should be further explored. PubMed","prediction_labels":"HUMAN"},{"cleaned":"increased multimodality treatment options improved survival hepatocellular carcinoma poor survival biliary tract cancers remains unchanged background primary hepatobiliary cancer incidence uk rising survival rates low surgery main curative option cancers multimodality therapies expanding aim original study determine trends survival 8 year period patients treated primary hepatobiliary cancers tertiary referral centre method patients treated common types primary hepatobiliary cancers namely hepatocellular carcinoma hcc cholangiocarcinoma gallbladder cancer january 2009 december 2016 retrospectively analysed prospective database linked uk hospital episode statistics data results total 1536 patients primary hepatobiliary cancers assessed treatment plans formulated supra regional specialist hepatobiliary mdt primary hepatobiliary cancers treated hcc n 836 cholangiocarcinoma n 516 gallbladder cancer n 184 survival 3 cancers significantly better curative treatment overall median survival times 350 180 150 days respectively hcc cholangiocarcinoma gallbladder cancer excluding best supportive care patients respective survival figures 900 600 400 days survival hcc patients improved time significantly increased final 3 years study p 0 011 cholangiocarcinoma gallbladder cancer survivals poor change significantly time conclusion hcc outcome improved association expanded multimodal therapies survivals cholangiocarcinoma gallbladder cancer remain poor parallel limited expansion multimodal therapies highlighting unmet therapeutic need biliary tract cancers stn","probabilities":0.9799733,"Title":"Increased Multimodality Treatment Options Has Improved Survival For Hepatocellular Carcinoma But Poor Survival For Biliary Tract Cancers Remains Unchanged","Abstract":"Background: Primary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre. \r\n\r\n Method: Patients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data. \r\n\r\n Results: A total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time. \r\n\r\n Conclusion: HCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers.","Source":"STN","category":"HUMAN","training_data":"Increased Multimodality Treatment Options Has Improved Survival For Hepatocellular Carcinoma But Poor Survival For Biliary Tract Cancers Remains Unchanged Background: Primary hepatobiliary cancer incidence in the UK is rising and survival rates are low. Surgery is the main curative option for these cancers, but multimodality therapies are expanding. The aim of our original study was to determine trends in survival, over an 8-year period, of patients treated for primary hepatobiliary cancers at our tertiary referral Centre. \r\n\r\n Method: Patients treated for the most common types of primary hepatobiliary cancers, namely Hepatocellular carcinoma (HCC), Cholangiocarcinoma and Gallbladder cancer between January 2009 and December 2016 were retrospectively analysed from a prospective database linked to UK Hospital Episode Statistics data. \r\n\r\n Results: A total of 1536 patients with primary hepatobiliary cancers were assessed and treatment plans formulated at our supra-regional specialist Hepatobiliary MDT. The primary hepatobiliary cancers treated were HCC (n = 836), Cholangiocarcinoma (n = 516), and Gallbladder cancer (n = 184). Survival for all the 3 cancers was significantly better with curative treatment. Overall median survival times were 350, 180, and 150 days respectively for HCC, Cholangiocarcinoma and Gallbladder cancer. Excluding best supportive care patients, the respective survival figures were 900, 600, and 400 days. Survival for HCC patients improved over time and was significantly increased in the final 3 years of the study (p ≤ 0.011 for all). Cholangiocarcinoma and Gallbladder cancer survivals were poor and did not change significantly over time. \r\n\r\n Conclusion: HCC outcome has improved in association with expanded multimodal therapies. Survivals for cholangiocarcinoma and gallbladder cancer remain poor in parallel with limited expansion of multimodal therapies highlighting an unmet therapeutic need for biliary tract cancers. STN","prediction_labels":"HUMAN"},{"cleaned":"trend analysis survival primary gallbladder cancer united states 1973 2009 population based study primary gallbladder cancer aggressive uncommon cancer poor outcomes study examines epidemiology trend survival gallbladder cancer united states 1973 2009 utilized surveillance epidemiology end results database seer frequency rate analyses demographics stage survival compared among non hispanic whites hispanics african american asian pacific islanders total 18 124 cases reported seer 1973 2009 comprising 1 4 reported gastrointestinal cancers gallbladder cancer common females males 71 vs 29 respectively age adjusted incidence rate 1 4 per 100 000 significantly higher females males 1 7 vs 1 0 trend analysis showed incidence rate decreasing last three decades males however among females incidence rate decreased 1973 mid 90s remained stable since trend analysis stage diagnosis showed proportion late stage cases increasing significantly since 2001 decreasing pattern since 1973 survival improved considerably time survival better females males asian pacific islanders racial groups highest survival patients received surgery radiation trend analysis revealed recent increase incidence late stage gallbladder cancer highest survival associated receiving surgery radiation stn","probabilities":0.9799733,"Title":"Trend Analysis And Survival Of Primary Gallbladder Cancer In The United States: A 1973-2009 Population-Based Study","Abstract":"Primary gallbladder cancer is an aggressive and uncommon cancer with poor outcomes. Our study examines epidemiology, trend, and survival of gallbladder cancer in the United States from 1973 to 2009. We utilized the Surveillance Epidemiology and End Results database (SEER). Frequency and rate analyses on demographics, stage, and survival were compared among non-Hispanic whites, Hispanics, African American, and Asian/Pacific Islanders. A total of 18,124 cases were reported in SEER from 1973 to 2009 comprising 1.4% of all reported gastrointestinal cancers. Gallbladder cancer was more common in females than males (71 vs. 29%, respectively). The age-adjusted incidence rate was 1.4 per 100,000, significantly higher in females than males (1.7 vs. 1.0). Trend analysis showed that the incidence rate has been decreasing over the last three decades for males. However, among females, the incidence rate had decreased from 1973 to mid-90s but has remained stable since then. Trend analysis for stage at diagnosis showed that the proportion of late-stage cases has been increasing significantly since 2001 after a decreasing pattern since 1973. Survival has improved considerably over time, and survival is better in females than males and in Asian/Pacific Islanders than other racial groups. The highest survival was in patients who received both surgery and radiation. Trend analysis revealed a recent increase of the incidence of late-stage gallbladder cancer. Highest survival was associated with receiving both surgery and radiation.","Source":"STN","category":"HUMAN","training_data":"Trend Analysis And Survival Of Primary Gallbladder Cancer In The United States: A 1973-2009 Population-Based Study Primary gallbladder cancer is an aggressive and uncommon cancer with poor outcomes. Our study examines epidemiology, trend, and survival of gallbladder cancer in the United States from 1973 to 2009. We utilized the Surveillance Epidemiology and End Results database (SEER). Frequency and rate analyses on demographics, stage, and survival were compared among non-Hispanic whites, Hispanics, African American, and Asian/Pacific Islanders. A total of 18,124 cases were reported in SEER from 1973 to 2009 comprising 1.4% of all reported gastrointestinal cancers. Gallbladder cancer was more common in females than males (71 vs. 29%, respectively). The age-adjusted incidence rate was 1.4 per 100,000, significantly higher in females than males (1.7 vs. 1.0). Trend analysis showed that the incidence rate has been decreasing over the last three decades for males. However, among females, the incidence rate had decreased from 1973 to mid-90s but has remained stable since then. Trend analysis for stage at diagnosis showed that the proportion of late-stage cases has been increasing significantly since 2001 after a decreasing pattern since 1973. Survival has improved considerably over time, and survival is better in females than males and in Asian/Pacific Islanders than other racial groups. The highest survival was in patients who received both surgery and radiation. Trend analysis revealed a recent increase of the incidence of late-stage gallbladder cancer. Highest survival was associated with receiving both surgery and radiation. STN","prediction_labels":"HUMAN"},{"cleaned":"staging survival resected hilar cholangiocarcinoma analysis 80 consecutive patients introduction predicting long term survival hilar cholangiocarcinoma difficult revised ajcc staging system extensively evaluated may correlate clinical outcomes alternative staging system incorporates factors related local tumor extent including portal vein invasion lobar atrophy proposed aim study evaluate current staging systems hilar cholangiocarcinoma identify clinical factors associated improved survival methods retrospective cohort study clinical pathologic characteristics obtained resected patients bismuth corlette type iiia iiib hilar cholangiocarcinoma 1993 2011 patientswerestratifiedbythe7theditionajcctnmstagingparametersandbythemodified blumgart staging system includes portal vein invasion presence lobar atrophy univariate multivariate analyses used test effects clinicopathologic factors staging systems overall survival results eighty consecutive patients median age 64 years range 36 82 64 male underwent anatomic hepatectomy bile duct resection reconstruction bismuth corlette iiia 51 bismuth corlette iiib 49 cholangiocarcinoma margin negative resection achieved 94 resections 30 day mortality 10 median follow 26 months range 0 181 months overall median survival 34 months twenty three percent patients welldifferentiatedcholangiocarcinoma theajccstagingsystemstratifiedpatientsintofollowing groups t1 26 t2 58 t3 16 n0 61 n1 39 stage 20 stage ii 30 stage iii 50 none patients distant metastases time resection kaplan meier estimates demonstrate association survival ajcc staging parameters p 0 121 blumgart staging system stratified patients following groups blumgart t1 58 blumgart t2 41 one patient blumgart t3 cholangiocarcinoma invasion portal vein bifurcation univariate analyses demonstrated association survival tumor grade p 0 033 blumgart stage p 0 010 one five year survival estimates blumgart t1 blumgart t2 t3 86 47 vs 74 17 p 0 010 adjusting tumor grade blumgart t2 t3 stage correlated increasedlikelihoodofmortality hr 1 93 95 ci 1 09 3 42 p 0 024 conclusions current ajcc tnm staging system predict survival current study blumgart staging system emphasizes portal vein invasion lobar atrophy predicted overall survival independent clinical pathologic factors inclusion lobar atrophy classification might improve accuracy ajcc system help define prognosis patients hilar cholangiocarcinoma google scholar","probabilities":0.9799733,"Title":"Staging And Survival Of Resected Hilar Cholangiocarcinoma: An Analysis Of 80 Consecutive Patients","Abstract":"Introduction: Predicting long-term survival in hilar cholangiocarcinoma is difficult. The revised AJCC staging system has not been extensively evaluated and may not correlate with clinical outcomes. An alternative staging system which incorporates factors related to local tumor extent, including portal vein invasion and lobar atrophy, has been proposed. The aim of this study was to evaluate current staging systems for hilar cholangiocarcinoma and identify clinical factors associated with improved survival. Methods: In this retrospective cohort study, clinical and pathologic characteristics were obtained for all resected patients with Bismuth-Corlette Type IIIa and IIIb hilar cholangiocarcinoma from 1993 to 2011. Patientswerestratifiedbythe7theditionAJCCTNMstagingparametersandbythemodified Blumgart staging system which includes portal vein invasion and presence of lobar atrophy. Univariate and multivariate analyses were used to test effects of clinicopathologic factors and staging systems on overall survival. Results: Eighty consecutive patients (median age 64 years (range 36-82), 64% male) underwent an anatomic hepatectomy with a bile duct resection and reconstruction for Bismuth-Corlette IIIa (51%) and Bismuth-Corlette IIIb (49%) cholangiocarcinoma. Margin negative resection was achieved in 94% of resections; 30-day mortality was 10%. Median follow-up was 26 months (range 0-181 months) with overall median survival of 34 months. Twenty-three percent of the patients had welldifferentiatedcholangiocarcinoma.TheAJCCstagingsystemstratifiedpatientsintofollowing groups: T1-26%, T2-58%, T3-16%; N0-61%, N1-39%; Stage I-20%, Stage II-30%, Stage III-50%. None of the patients had distant metastases at the time of resection. Kaplan-Meier estimates did not demonstrate an association between survival and AJCC staging parameters (all p≥0.121). Blumgart staging system stratified patients into following groups: Blumgart T1 - 58%, Blumgart T2 - 41%; one patient had a Blumgart T3 cholangiocarcinoma with invasion into portal vein bifurcation. Univariate analyses demonstrated an association of survival with tumor grade (p=0.033) and Blumgart T-stage (p=0.010). One- and five-year survival estimates for Blumgart T1 and Blumgart T2/T3 were 86% and 47% vs. 74% and 17% (p=0.010). After adjusting for tumor grade, Blumgart T2/T3 stage correlated with increasedlikelihoodofmortality(HR=1.93,95%CI:1.09-3.42,p=0.024)Conclusions:While the current AJCC TNM staging system did not predict survival in the current study, the Blumgart staging system which emphasizes portal vein invasion and lobar atrophy predicted overall survival independent of other clinical and pathologic factors. Inclusion of lobar atrophy into the T classification might improve accuracy of the AJCC system, and help define prognosis in patients with hilar cholangiocarcinoma","Source":"Google Scholar","category":"HUMAN","training_data":"Staging And Survival Of Resected Hilar Cholangiocarcinoma: An Analysis Of 80 Consecutive Patients Introduction: Predicting long-term survival in hilar cholangiocarcinoma is difficult. The revised AJCC staging system has not been extensively evaluated and may not correlate with clinical outcomes. An alternative staging system which incorporates factors related to local tumor extent, including portal vein invasion and lobar atrophy, has been proposed. The aim of this study was to evaluate current staging systems for hilar cholangiocarcinoma and identify clinical factors associated with improved survival. Methods: In this retrospective cohort study, clinical and pathologic characteristics were obtained for all resected patients with Bismuth-Corlette Type IIIa and IIIb hilar cholangiocarcinoma from 1993 to 2011. Patientswerestratifiedbythe7theditionAJCCTNMstagingparametersandbythemodified Blumgart staging system which includes portal vein invasion and presence of lobar atrophy. Univariate and multivariate analyses were used to test effects of clinicopathologic factors and staging systems on overall survival. Results: Eighty consecutive patients (median age 64 years (range 36-82), 64% male) underwent an anatomic hepatectomy with a bile duct resection and reconstruction for Bismuth-Corlette IIIa (51%) and Bismuth-Corlette IIIb (49%) cholangiocarcinoma. Margin negative resection was achieved in 94% of resections; 30-day mortality was 10%. Median follow-up was 26 months (range 0-181 months) with overall median survival of 34 months. Twenty-three percent of the patients had welldifferentiatedcholangiocarcinoma.TheAJCCstagingsystemstratifiedpatientsintofollowing groups: T1-26%, T2-58%, T3-16%; N0-61%, N1-39%; Stage I-20%, Stage II-30%, Stage III-50%. None of the patients had distant metastases at the time of resection. Kaplan-Meier estimates did not demonstrate an association between survival and AJCC staging parameters (all p≥0.121). Blumgart staging system stratified patients into following groups: Blumgart T1 - 58%, Blumgart T2 - 41%; one patient had a Blumgart T3 cholangiocarcinoma with invasion into portal vein bifurcation. Univariate analyses demonstrated an association of survival with tumor grade (p=0.033) and Blumgart T-stage (p=0.010). One- and five-year survival estimates for Blumgart T1 and Blumgart T2/T3 were 86% and 47% vs. 74% and 17% (p=0.010). After adjusting for tumor grade, Blumgart T2/T3 stage correlated with increasedlikelihoodofmortality(HR=1.93,95%CI:1.09-3.42,p=0.024)Conclusions:While the current AJCC TNM staging system did not predict survival in the current study, the Blumgart staging system which emphasizes portal vein invasion and lobar atrophy predicted overall survival independent of other clinical and pathologic factors. Inclusion of lobar atrophy into the T classification might improve accuracy of the AJCC system, and help define prognosis in patients with hilar cholangiocarcinoma Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"prognostic model adopting new criteria invasion depth distal bile duct cancer better predictor survival previous methods background aims depth invasion important prognostic factor patients distal bile duct dbd carcinoma study aims identify optimal meth od measuring depth invasion relation prognosis patients dbd cancer methods data 179 patients dbd adenocarcinoma treated three institutions korea 2003 2015 stored database pathologic review depth vasion measured relationships clin icopathological parameters groups based vasion depth g1 3mm g2 3 10mm g3 10mm evaluated survival time group based invasion depth classification compared results deeply invading tumor exhibit ten dency towards infiltrative pattern higher histological grade nodal metastasis pancreatic duodenal lympho vascular perineural invasions univariate analysis depth invasion well current ajcc staging system significantly correlated worse re lapse free overall survival p 0 05 adjust ing confounders grouping based invasion depth re mained one prognostic factors p 0 05 category significant conclusions grouping based invasion depth clear meaningful concept overcoming vagueness classification predicting clinical outcomes patients dbd carcinoma invasion depth measured histopathological assess ment dbd carcinomas google scholar","probabilities":0.9799733,"Title":"A Prognostic Model Adopting New Criteria Of Invasion Depth In Distal Bile Duct Cancer: A Better Predictor Of Survival Than Previous Methods","Abstract":"Background / aims: \nDepth of invasion is an important \nprognostic factor for patients with distal bile duct (DBD) \ncarcinoma. This study aims to identify an optimal meth-\nod of measuring the depth of invasion in relation to the \nprognosis in patients with DBD cancer. \nMethods: \nData of 179 patients with DBD adenocarcinoma \ntreated in three institutions in Korea (2003-2015) were \nstored in a database. At pathologic review, depth of in-\nvasion was measured. The relationships between clin-\nicopathological parameters and groups based on in-vasion depth (G1, \n≤\n3mm; G2, 3-10mm; G3 >10mm) \nwere evaluated, and the survival time of each group based \non invasion depth and T classification was compared. \nResults: \nThe deeply invading tumor exhibit more ten-\ndency towards infiltrative pattern, higher histological \ngrade, nodal metastasis, pancreatic, duodenal, lympho-\nvascular, perineural invasions. In univariate analysis, the \ndepth of invasion as well as the current AJCC T-staging \nsystem was significantly correlated with worse re-\nlapse-free and overall survival (all. \np\n<0.05). After adjust-\ning confounders, grouping based on invasion depth re-\nmained as one of the prognostic factors (all, \np\n<0.05), \nwhile that of T category was not significant. \nConclusions: \nThe grouping based on invasion depth \ncould be a clear and meaningful concept overcoming the \nvagueness of the T classification in predicting clinical \noutcomes in patients with DBD carcinoma. Invasion \ndepth should be measured on histopathological assess-\nment of DBD carcinomas.","Source":"Google Scholar","category":"HUMAN","training_data":"A Prognostic Model Adopting New Criteria Of Invasion Depth In Distal Bile Duct Cancer: A Better Predictor Of Survival Than Previous Methods Background / aims: \nDepth of invasion is an important \nprognostic factor for patients with distal bile duct (DBD) \ncarcinoma. This study aims to identify an optimal meth-\nod of measuring the depth of invasion in relation to the \nprognosis in patients with DBD cancer. \nMethods: \nData of 179 patients with DBD adenocarcinoma \ntreated in three institutions in Korea (2003-2015) were \nstored in a database. At pathologic review, depth of in-\nvasion was measured. The relationships between clin-\nicopathological parameters and groups based on in-vasion depth (G1, \n≤\n3mm; G2, 3-10mm; G3 >10mm) \nwere evaluated, and the survival time of each group based \non invasion depth and T classification was compared. \nResults: \nThe deeply invading tumor exhibit more ten-\ndency towards infiltrative pattern, higher histological \ngrade, nodal metastasis, pancreatic, duodenal, lympho-\nvascular, perineural invasions. In univariate analysis, the \ndepth of invasion as well as the current AJCC T-staging \nsystem was significantly correlated with worse re-\nlapse-free and overall survival (all. \np\n<0.05). After adjust-\ning confounders, grouping based on invasion depth re-\nmained as one of the prognostic factors (all, \np\n<0.05), \nwhile that of T category was not significant. \nConclusions: \nThe grouping based on invasion depth \ncould be a clear and meaningful concept overcoming the \nvagueness of the T classification in predicting clinical \noutcomes in patients with DBD carcinoma. Invasion \ndepth should be measured on histopathological assess-\nment of DBD carcinomas. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"antitumor effects candidone natural flavanone derivative cholangiocarcinoma cells abstract available google scholar","probabilities":0.9799733,"Title":"Antitumor Effects Of Candidone A Natural Flavanone Derivative In Cholangiocarcinoma Cells","Abstract":"Abstract not available","Source":"Google Scholar","category":"ANIMAL","training_data":"Antitumor Effects Of Candidone A Natural Flavanone Derivative In Cholangiocarcinoma Cells Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"duration inflammatory bowel disease associated increased risk cholangiocarcinoma patients primary sclerosing cholangitis ibd objectives primary sclerosing cholangitis psc often coexists inflammatory bowel disease ibd complicated cholangiocarcinoma cca lethal malignancy reliable predictors remain unknown aimed characterize influence colectomy ibd duration risk cca patients psc ibd methods retrospective review patients psc ibd seen mayo clinic rochester january 2005 may 2013 performed primary outcome time development cca goal determine whether risk differed patients without colectomy risk factors assessed using univariable multivariable cox proportional hazard models colectomy ibd disease duration development advanced liver disease treated time dependent covariates results total 399 patients psc ibd included study 137 colectomy 123 patients developed cca age adjusted univariate cox proportional hazard models demonstrated colectomy hazard ratio hr 1 53 95 confidence interval ci 1 05 2 22 p 0 02 duration ibd hr 1 37 95 ci 1 15 1 63 p 0 01 associated increased risk cca colonic neoplasia hr 1 52 95 ci 0 97 2 37 p 0 06 colectomy colonic neoplasia hr 1 62 95 ci 1 01 2 61 p 0 05 approached significance among patients history colectomy colonic neoplasia indication surgery associated particularly increased risk cca hr 2 91 95 ci 1 24 6 84 p 0 01 compared medically refractory disease multivariate analysis duration ibd remained significantly associated cca hr 1 33 95 ci 1 11 1 60 p 0 01 influence ibd duration cca risk modified colectomy p 0 69 conclusions prolonged duration ibd associated increased risk cca patients psc ibd colectomy modify risk findings identify subset patients high risk lethal complication need close surveillance stn","probabilities":0.9799733,"Title":"Duration Of Inflammatory Bowel Disease Is Associated With Increased Risk Of Cholangiocarcinoma In Patients With Primary Sclerosing Cholangitis And Ibd","Abstract":"Objectives: Primary sclerosing cholangitis (PSC) often coexists with inflammatory bowel disease (IBD) and can be complicated by cholangiocarcinoma (CCA), a lethal malignancy for which reliable predictors remain unknown. We aimed to characterize the influence of colectomy and IBD duration on risk of CCA in patients with PSC-IBD. \r\n\r\n Methods: A retrospective review of patients with PSC-IBD seen at the Mayo Clinic, Rochester, between January 2005 and May 2013 was performed. The primary outcome was time to development of CCA and our goal was to determine whether the risk differed between patients with and without colectomy. Risk factors were assessed using univariable and multivariable Cox proportional hazard models where colectomy, IBD disease duration, and development of advanced liver disease were treated as time-dependent covariates. \r\n\r\n Results: A total of 399 patients with PSC-IBD were included in the study, of whom 137 had a colectomy and 123 patients developed CCA. Age-adjusted univariate Cox proportional hazard models demonstrated that colectomy (hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.05-2.22, P=0.02) and duration of IBD (HR 1.37, 95% CI 1.15-1.63, P<0.01) were associated with an increased risk of CCA, and colonic neoplasia (HR 1.52, 95% CI 0.97-2.37, P=0.06) and colectomy for colonic neoplasia (HR 1.62, 95% CI 1.01-2.61, P=0.05) approached significance. Among patients with a history of colectomy, colonic neoplasia as the indication for surgery was associated with a particularly increased risk of CCA (HR 2.91, 95% CI 1.24-6.84, P=0.01) compared with medically refractory disease. On multivariate analysis, duration of IBD remained significantly associated with CCA (HR 1.33, 95% CI 1.11-1.60, P<0.01). The influence of IBD duration on CCA risk was not modified after colectomy (P=0.69). \r\n\r\n Conclusions: Prolonged duration of IBD is associated with an increased risk of CCA in patients with PSC-IBD, and colectomy itself does not modify this risk. These findings identify a subset of patients who are at high risk of this lethal complication and in need of close surveillance.","Source":"STN","category":"HUMAN","training_data":"Duration Of Inflammatory Bowel Disease Is Associated With Increased Risk Of Cholangiocarcinoma In Patients With Primary Sclerosing Cholangitis And Ibd Objectives: Primary sclerosing cholangitis (PSC) often coexists with inflammatory bowel disease (IBD) and can be complicated by cholangiocarcinoma (CCA), a lethal malignancy for which reliable predictors remain unknown. We aimed to characterize the influence of colectomy and IBD duration on risk of CCA in patients with PSC-IBD. \r\n\r\n Methods: A retrospective review of patients with PSC-IBD seen at the Mayo Clinic, Rochester, between January 2005 and May 2013 was performed. The primary outcome was time to development of CCA and our goal was to determine whether the risk differed between patients with and without colectomy. Risk factors were assessed using univariable and multivariable Cox proportional hazard models where colectomy, IBD disease duration, and development of advanced liver disease were treated as time-dependent covariates. \r\n\r\n Results: A total of 399 patients with PSC-IBD were included in the study, of whom 137 had a colectomy and 123 patients developed CCA. Age-adjusted univariate Cox proportional hazard models demonstrated that colectomy (hazard ratio (HR) 1.53, 95% confidence interval (CI) 1.05-2.22, P=0.02) and duration of IBD (HR 1.37, 95% CI 1.15-1.63, P<0.01) were associated with an increased risk of CCA, and colonic neoplasia (HR 1.52, 95% CI 0.97-2.37, P=0.06) and colectomy for colonic neoplasia (HR 1.62, 95% CI 1.01-2.61, P=0.05) approached significance. Among patients with a history of colectomy, colonic neoplasia as the indication for surgery was associated with a particularly increased risk of CCA (HR 2.91, 95% CI 1.24-6.84, P=0.01) compared with medically refractory disease. On multivariate analysis, duration of IBD remained significantly associated with CCA (HR 1.33, 95% CI 1.11-1.60, P<0.01). The influence of IBD duration on CCA risk was not modified after colectomy (P=0.69). \r\n\r\n Conclusions: Prolonged duration of IBD is associated with an increased risk of CCA in patients with PSC-IBD, and colectomy itself does not modify this risk. These findings identify a subset of patients who are at high risk of this lethal complication and in need of close surveillance. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic model predict cancer specific survival patients gallbladder carcinoma surgery population based analysis predicting prognosis gallbladder carcinoma gbc always important improving survival objective study determine risk factors survival patients gbc surgery develop predictive nomograms overall survival os cancer specific survival css using large population based cohort identified 2 762 patients primary resectable gbc surveillance epidemiology end results seer database period 2004 2014 another 152 patients gbc surgery sun yat sen university cancer center sysucc period 1997 2017 1 2 3 year cancer specific mortalities 37 2 52 9 59 9 competing mortalities 5 8 7 8 9 0 respectively nomograms developed estimate os css validated concordance indexes c indexes evaluated using receiver operating characteristic roc curves c indexes nomograms os css prediction 0 704 0 732 respectively addition compared 8th tumor node metastasis staging system newly established nomograms displayed higher areas roc curves os pfs prediction nomograms well validated thus aid individual clinical practice stn","probabilities":0.9799733,"Title":"Prognostic Model To Predict Cancer-Specific Survival For Patients With Gallbladder Carcinoma After Surgery: A Population-Based Analysis","Abstract":"Predicting the prognosis of gallbladder carcinoma (GBC) has always been important for improving survival. The objective of this study was to determine the risk factors of survival for patients with GBC after surgery and to develop predictive nomograms for overall survival (OS) and cancer-specific survival (CSS) using a large population-based cohort. We identified 2,762 patients with primary resectable GBC in the Surveillance, Epidemiology, and End Results (SEER) database for the period of 2004 to 2014 and another 152 patients with GBC after surgery from Sun Yat-sen University Cancer Center (SYSUCC) for the period of 1997 to 2017. The 1-, 2-, and 3-year cancer-specific mortalities were 37.2, 52.9, and 59.9%, while the competing mortalities were 5.8, 7.8, and 9.0%, respectively. Nomograms were developed to estimate OS and CSS, and these were validated by concordance indexes (C-indexes) and evaluated using receiver operating characteristic (ROC) curves. The C-indexes of the nomograms for OS and CSS prediction were 0.704 and 0.732, respectively. In addition, compared with the 8th Tumor-Node-Metastasis staging system, the newly established nomograms displayed higher areas under the ROC curves for OS and PFS prediction. The nomograms are well-validated and could thus aid individual clinical practice.","Source":"STN","category":"HUMAN","training_data":"Prognostic Model To Predict Cancer-Specific Survival For Patients With Gallbladder Carcinoma After Surgery: A Population-Based Analysis Predicting the prognosis of gallbladder carcinoma (GBC) has always been important for improving survival. The objective of this study was to determine the risk factors of survival for patients with GBC after surgery and to develop predictive nomograms for overall survival (OS) and cancer-specific survival (CSS) using a large population-based cohort. We identified 2,762 patients with primary resectable GBC in the Surveillance, Epidemiology, and End Results (SEER) database for the period of 2004 to 2014 and another 152 patients with GBC after surgery from Sun Yat-sen University Cancer Center (SYSUCC) for the period of 1997 to 2017. The 1-, 2-, and 3-year cancer-specific mortalities were 37.2, 52.9, and 59.9%, while the competing mortalities were 5.8, 7.8, and 9.0%, respectively. Nomograms were developed to estimate OS and CSS, and these were validated by concordance indexes (C-indexes) and evaluated using receiver operating characteristic (ROC) curves. The C-indexes of the nomograms for OS and CSS prediction were 0.704 and 0.732, respectively. In addition, compared with the 8th Tumor-Node-Metastasis staging system, the newly established nomograms displayed higher areas under the ROC curves for OS and PFS prediction. The nomograms are well-validated and could thus aid individual clinical practice. STN","prediction_labels":"HUMAN"},{"cleaned":"regulated phosphoglycerate kinase 1 expression associated poor prognosis patients gallbladder cancer evaluate prognostic significance phosphoglycerate kinase 1 pgk1 protein expression patients gallbladder cancer gbc ninety five patients underwent surgical resection gbc january 2004 december 2010 enrolled overall survival os disease free survival dfs evaluated 10 year follow pgk1 expression assessed tissue microarray immunohistochemistry prognostic significance analyzed using multivariate cox regression pgk1 highly expressed gallbladder mucosa decreased pgk1 expression detected 54 7 52 95 patients gbc significantly regulated gbc samples compared gallbladder mucosa p 0 0001 associated multiple clinicopathological factors multivariate survival analysis showed low pgk1 expression associated shorter os median 12 8 vs 45 4 months hazard ratio hr 3 077 95 confidence interval ci 1 373 6 897 p 0 006 dfs median 8 3 vs 37 9 months hr 2 988 95 ci 1 315 6 790 p 0 009 indicating pgk1 expression independent prognostic factor patients gbc low pgk1 expression associated progression patients gbc pgk1 expression useful prognostic biomarker gbc pubmed","probabilities":0.7966102,"Title":"Down-Regulated Phosphoglycerate Kinase 1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Cancer","Abstract":"To evaluate prognostic significance of phosphoglycerate kinase 1 (PGK1) protein expression in patients with gallbladder cancer (GBC).Ninety-five patients who underwent surgical resection for GBC between January 2004 and December 2010 were enrolled. Overall survival (OS) and disease-free survival (DFS) were evaluated over a 10-year follow-up. PGK1 expression was assessed by tissue microarray and immunohistochemistry. Prognostic significance was analyzed using multivariate Cox regression.PGK1 was highly expressed in all gallbladder mucosa. Decreased PGK1 expression was detected in 54.7% (52/95) of patients with GBC. It was significantly down-regulated in GBC samples compared with that in gallbladder mucosa (P < 0.0001), and was associated with multiple clinicopathological factors. Multivariate survival analysis showed that low PGK1 expression was associated with shorter OS (median 12.8 vs 45.4 months; hazard ratio [HR] = 3.077; 95% confidence interval [CI], 1.373-6.897; P = 0.006) and DFS (median 8.3 vs 37.9 months; HR = 2.988; 95% CI, 1.315-6.790; P = 0.009), indicating that PGK1 expression was an independent prognostic factor in patients with GBC.Low PGK1 expression was associated with progression in patients with GBC. PGK1 expression could be a useful prognostic biomarker for GBC.","Source":"PubMed","category":"HUMAN","training_data":"Down-Regulated Phosphoglycerate Kinase 1 Expression Is Associated With Poor Prognosis in Patients With Gallbladder Cancer To evaluate prognostic significance of phosphoglycerate kinase 1 (PGK1) protein expression in patients with gallbladder cancer (GBC).Ninety-five patients who underwent surgical resection for GBC between January 2004 and December 2010 were enrolled. Overall survival (OS) and disease-free survival (DFS) were evaluated over a 10-year follow-up. PGK1 expression was assessed by tissue microarray and immunohistochemistry. Prognostic significance was analyzed using multivariate Cox regression.PGK1 was highly expressed in all gallbladder mucosa. Decreased PGK1 expression was detected in 54.7% (52/95) of patients with GBC. It was significantly down-regulated in GBC samples compared with that in gallbladder mucosa (P < 0.0001), and was associated with multiple clinicopathological factors. Multivariate survival analysis showed that low PGK1 expression was associated with shorter OS (median 12.8 vs 45.4 months; hazard ratio [HR] = 3.077; 95% confidence interval [CI], 1.373-6.897; P = 0.006) and DFS (median 8.3 vs 37.9 months; HR = 2.988; 95% CI, 1.315-6.790; P = 0.009), indicating that PGK1 expression was an independent prognostic factor in patients with GBC.Low PGK1 expression was associated with progression in patients with GBC. PGK1 expression could be a useful prognostic biomarker for GBC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ampullary carcinoma genetic perspective ampulla vater carcinoma avc rare gastrointestinal tumour associated high mortality rate often diagnosed later stages due lack clinical symptoms early diagnosis condition essential effectively treat patients better prognosis significant amount advancement made understanding molecular nature cancer past decade substantial number mutations alterations detected various tumors despite occurrence avc across globe number studies conducted tumor type remains low largely due rare occurrence moreover avc tissues complex contain mutations oncogenes tumour suppressors apoptotic proteins cell proliferation proteins cell signaling proteins transcription factors chromosomal abnormalities cellular adhesion proteins frequently mutated genes included kras tp53 smad4 associated prognosis several molecules pi3k wnt signaling tgf beta pathway cell cycle also altered avcs review comprises genetic mutations associated pathways related prognosis involved avcs year 1989 2017 report used stepping stone establish biomarkers early diagnosis avc discover molecular targets drug therapy pubmed","probabilities":0.962963,"Title":"Ampullary carcinoma-A genetic perspective","Abstract":"Ampulla of vater carcinoma (AVC) is a rare gastrointestinal tumour that is associated with a high mortality rate and it's often diagnosed at later stages due to lack of clinical symptoms. Early diagnosis of this condition is essential to effectively treat patients for better prognosis. A significant amount of advancement has been made in understanding the molecular nature of cancer in the past decade. A substantial number of mutations and alterations have been detected in various tumors. Despite the occurrence of AVC across the globe, the number of studies conducted on this tumor type remains low; this is largely due to its rare occurrence. Moreover, AVC tissues are complex and contain mutations in oncogenes, tumour suppressors, apoptotic proteins, cell proliferation proteins, cell signaling proteins, transcription factors, chromosomal abnormalities and cellular adhesion proteins. The frequently mutated genes included KRAS, TP53 and SMAD4 and are associated with prognosis. Several molecules of the PI3K, Wnt signaling, TGF-beta pathway and cell cycle have also been altered in AVCs. This review comprises of all the genetic mutations, associated pathways and related prognosis that are involved in AVCs from the year 1989 to 2017. This report can be used as a stepping-stone to establish biomarkers for early diagnosis of AVC and to discover molecular targets for drug therapy.","Source":"PubMed","category":"HUMAN","training_data":"Ampullary carcinoma-A genetic perspective Ampulla of vater carcinoma (AVC) is a rare gastrointestinal tumour that is associated with a high mortality rate and it's often diagnosed at later stages due to lack of clinical symptoms. Early diagnosis of this condition is essential to effectively treat patients for better prognosis. A significant amount of advancement has been made in understanding the molecular nature of cancer in the past decade. A substantial number of mutations and alterations have been detected in various tumors. Despite the occurrence of AVC across the globe, the number of studies conducted on this tumor type remains low; this is largely due to its rare occurrence. Moreover, AVC tissues are complex and contain mutations in oncogenes, tumour suppressors, apoptotic proteins, cell proliferation proteins, cell signaling proteins, transcription factors, chromosomal abnormalities and cellular adhesion proteins. The frequently mutated genes included KRAS, TP53 and SMAD4 and are associated with prognosis. Several molecules of the PI3K, Wnt signaling, TGF-beta pathway and cell cycle have also been altered in AVCs. This review comprises of all the genetic mutations, associated pathways and related prognosis that are involved in AVCs from the year 1989 to 2017. This report can be used as a stepping-stone to establish biomarkers for early diagnosis of AVC and to discover molecular targets for drug therapy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"outcomes biliary malignancy biliary malignancies reviewed gallbladder cancer gbc intrahepatic cholangiocarcinoma ihc perihilar cholangiocarcinoma phc focus outcomes potentially curative resection biliary malignancies key outcomes postoperative mortality median 5 year overall survival os recurrence free survival recurrence patterns poor prognostic factors recurrence survival well prognostic models also discussed incidence biliary malignancies united states 5 100 000 postoperative mortality resection gbc ihc similar liver resections indications however 90 day postoperative mortality liver resection phc 10 gbc median os depends strongly stage ranges 8 months pt3 79 months pt1b median os resection ihc 30 months phc 38 months majority patients biliary malignancies develop recurrence resection patients gbc recur early median time recurrence 12 months versus 20 months ihc phc patients resected ihc phc locoregional recurrence site recurrence 60 patients versus 15 patients gbc poor prognostic factors resection biliary malignancies include presence lymph node metastasis positive surgical resection margin moderate poor tumor differentiation several prognostic nomograms developed predict long term outcomes biliary cancer resection pubmed","probabilities":0.9799733,"Title":"Outcomes in biliary malignancy","Abstract":"The biliary malignancies that are reviewed here are gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (IHC), and perihilar cholangiocarcinoma (PHC). The focus is on outcomes after potentially curative resection of biliary malignancies. Key outcomes are postoperative mortality, median and 5-year overall survival (OS), recurrence-free survival, and recurrence patterns. Poor prognostic factors for recurrence and survival as well as prognostic models are also discussed. The incidence of biliary malignancies in the United States is about 5 in 100,000. Postoperative mortality for resection of GBC and IHC is similar to that of liver resections for other indications. However, 90 day postoperative mortality after liver resection for PHC is about 10%. For GBC, median OS depends strongly on the T-stage and ranges from 8 months (pT3) to 79 months (pT1b). Median OS after resection for IHC is about 30 months, and for PHC about 38 months. The majority of patients with biliary malignancies develop a recurrence after resection. Patients with GBC recur early with a median time to recurrence of 12 months, versus about 20 months for IHC and PHC. In patients with resected IHC or PHC locoregional recurrence was the only site of recurrence in about 60% of patients, versus 15% in patients with GBC. Poor prognostic factors after resection of all biliary malignancies include the presence of lymph node metastasis, a positive surgical resection margin, and moderate or poor tumor differentiation. Several prognostic nomograms have been developed to predict long-term outcomes of biliary cancer resection.","Source":"PubMed","category":"HUMAN","training_data":"Outcomes in biliary malignancy The biliary malignancies that are reviewed here are gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (IHC), and perihilar cholangiocarcinoma (PHC). The focus is on outcomes after potentially curative resection of biliary malignancies. Key outcomes are postoperative mortality, median and 5-year overall survival (OS), recurrence-free survival, and recurrence patterns. Poor prognostic factors for recurrence and survival as well as prognostic models are also discussed. The incidence of biliary malignancies in the United States is about 5 in 100,000. Postoperative mortality for resection of GBC and IHC is similar to that of liver resections for other indications. However, 90 day postoperative mortality after liver resection for PHC is about 10%. For GBC, median OS depends strongly on the T-stage and ranges from 8 months (pT3) to 79 months (pT1b). Median OS after resection for IHC is about 30 months, and for PHC about 38 months. The majority of patients with biliary malignancies develop a recurrence after resection. Patients with GBC recur early with a median time to recurrence of 12 months, versus about 20 months for IHC and PHC. In patients with resected IHC or PHC locoregional recurrence was the only site of recurrence in about 60% of patients, versus 15% in patients with GBC. Poor prognostic factors after resection of all biliary malignancies include the presence of lymph node metastasis, a positive surgical resection margin, and moderate or poor tumor differentiation. Several prognostic nomograms have been developed to predict long-term outcomes of biliary cancer resection. PubMed","prediction_labels":"HUMAN"},{"cleaned":"long term survival outcomes liver transplantation klatskin tumour comparative study radical resection surgery objective compare survival results liver transplantation radical resection klatskin tumor based published literatures methods retrieved medline articles treatment klatskin tumor published january 1996 december 2014 choose literatures including liver transplantation radical resection review manager 5 0 software used perform meta analysis extracted data results performing meta analysis 11 studies including 676 patients found comparable patient survival rate liver transplantation group radical resection group 1 year rr 1 00 95 ci 0 82 1 23 p 0 97 3 year rr 1 15 95 ci 0 75 1 77 p 0 51 5 year rr 1 37 95 ci 0 74 2 53 p 0 32 respectively statistical significance overall survival rate shown 2 groups whether short term long time total survival trends show long time survival lt group better rr group potential longer survival time conclusions liver transplantation equivalent radical resection klatskin tumor treatment terms patient survival potential higher long term patient survival rate lower recurrence especially patients unrespectable kt insufficient liver function lt superior clinical outcome stn","probabilities":0.9799733,"Title":"Long-Term Survival Outcomes Of Liver Transplantation For Klatskin Tumour: A Comparative Study With Radical Resection Surgery","Abstract":"Objective: To compare the survival results of liver transplantation with radical resection for klatskin tumor based on the published literatures. \r\n\r\n Methods: We retrieved Medline for articles on treatment of klatskin tumor published from January 1996 to December 2014, and choose the literatures including liver transplantation and radical resection. Review Manager 5. 0 software was used to perform the Meta-analysis of the extracted data. \r\n\r\n Results: After performing meta-analysis of 11 studies including 676 patients, we found comparable patient survival rate between liver transplantation group and radical resection group (1-year RR:1. 00, 95% CI:0. 82 - 1. 23, P = 0. 97; 3-year RR:1. 15, 95% CI:0. 75 - 1. 77, P 0. 51, 5-year RR: 1. 37, 95% CI: 0. 74 - 2. 53, P = 0. 32, respectively). No statistical significance of overall survival rate were shown between this 2 groups whether in short-term or long-time, but the total survival trends show the long-time survival of LT group is better than that of RR group which has the potential longer survival time. \r\n\r\n Conclusions: Liver transplantation was equivalent to radical resection for klatskin tumor treatment in terms of patient survival, with potential higher long-term patient survival rate and lower recurrence. especially for the patients with unrespectable KT or insufficient liver function, LT is superior for clinical outcome.","Source":"STN","category":"HUMAN","training_data":"Long-Term Survival Outcomes Of Liver Transplantation For Klatskin Tumour: A Comparative Study With Radical Resection Surgery Objective: To compare the survival results of liver transplantation with radical resection for klatskin tumor based on the published literatures. \r\n\r\n Methods: We retrieved Medline for articles on treatment of klatskin tumor published from January 1996 to December 2014, and choose the literatures including liver transplantation and radical resection. Review Manager 5. 0 software was used to perform the Meta-analysis of the extracted data. \r\n\r\n Results: After performing meta-analysis of 11 studies including 676 patients, we found comparable patient survival rate between liver transplantation group and radical resection group (1-year RR:1. 00, 95% CI:0. 82 - 1. 23, P = 0. 97; 3-year RR:1. 15, 95% CI:0. 75 - 1. 77, P 0. 51, 5-year RR: 1. 37, 95% CI: 0. 74 - 2. 53, P = 0. 32, respectively). No statistical significance of overall survival rate were shown between this 2 groups whether in short-term or long-time, but the total survival trends show the long-time survival of LT group is better than that of RR group which has the potential longer survival time. \r\n\r\n Conclusions: Liver transplantation was equivalent to radical resection for klatskin tumor treatment in terms of patient survival, with potential higher long-term patient survival rate and lower recurrence. especially for the patients with unrespectable KT or insufficient liver function, LT is superior for clinical outcome. STN","prediction_labels":"HUMAN"},{"cleaned":"expression human equilibrative nucleoside transporter 1 hent1 associated overall survival advanced biliary tract carcinoma btc treated gemcitabine introduction outcome patients unresectable postoperative recurrent biliary tract carcinoma btc mostly miserable patients possible candidates palliative chemotherapy gemcitabine pyrimidine nucleoside analogue commonly used chemotherapeutic agent advanced btc gemcitabine transported cell mostly human equilibrative nucleoside transporter 1 hent1 hent1 expression demonstrated play important role predicting clinical outcome gemcitabine chemotherapy several types cancer aim present study investigate predictive marker good prognosis gemcitabine chemotherapy unresectable postoperative recurrent btc materials methods analysis performed samples 25 patients unresectable 6 patients postoperative recurrent 19 patients btc treated gemcitabine host institute january 1997 january 2011 hent1 expression levels tumors evaluated immunohistochemistry clinical histopathological variables analyzed evaluate predictive values survival results 25 tumor specimens 18 72 specimens positive hnet1 immunostaing 7 28 specimens classified negative statistical significant differences found expression hent1 patient characteristics gender age tumor stage lymph node stage lymph duct invasion vascular invasion perineural invasion univariate analysis hent1 expression significantly correlated overall survival os median os 15 3 versus 4 2 months respectively patients positive versus negative hent1 staining p 0 006 result multivariate analysis hent1 expression useful predictive marker good prognosis significant difference p 0 001 conclusions patients positive hent1 expression btc significantly longer survival gemcitabine chemotherapy patients negative hent1 expression results suggest hent1 expression advanced btc patients treated gemcitabine prognostic predictive indicator useful decide gemcitabine chemotherapy google scholar","probabilities":1.0,"Title":"The Expression Of Human Equilibrative Nucleoside Transporter 1 (Hent1) Is Associated With Overall Survival In Advanced Biliary Tract Carcinoma (Btc) Treated With Gemcitabine","Abstract":"[Introduction] The outcome of patients with unresectable and postoperative recurrent biliary tract carcinoma (BTC) is mostly miserable and most patients are possible candidates for palliative chemotherapy. Gemcitabine is a pyrimidine nucleoside analogue that is commonly used chemotherapeutic agent for advanced BTC. Gemcitabine is transported into the cell mostly by human equilibrative nucleoside transporter 1(hENT1). The hENT1 expression has been demonstrated to play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of the present study was to investigate a predictive marker for good prognosis of gemcitabine chemotherapy for unresectable and postoperative recurrent BTC. [Materials and methods] The analysis was performed on samples from 25 patients with unresectable (6 patients) and postoperative recurrent (19 patients) BTC treated with gemcitabine at the host institute between January 1997 and January 2011. The hENT1 expression levels in tumors were evaluated by immunohistochemistry. The clinical and histopathological variables were analyzed to evaluate predictive values for survival. [Results] Of the 25 tumor specimens, 18 (72%) specimens had positive hNET1 immunostaing, while 7 (28%) specimens were classified as negative. No statistical significant differences were found between the expression of hENT1 and patient characteristics (gender, age, tumor stage, lymph node stage, lymph duct invasion, vascular invasion, perineural invasion). In the univariate analysis, hENT1 expression was significantly correlated with overall survival (OS). The median OS was 15.3 versus 4.2 months, respectively in patients with positive versus negative hENT1 staining (p=0.006). As a result of multivariate analysis, hENT1 expression was useful as a predictive marker for good prognosis with significant difference (p<0.001). [Conclusions] Patients with positive hENT1 expression in BTC have a significantly longer survival after gemcitabine chemotherapy than patients with negative hENT1 expression. Our results suggest that hENT1 expression in advanced BTC patients treated with gemcitabine is a prognostic predictive indicator and is useful to decide gemcitabine chemotherapy.","Source":"Google Scholar","category":"HUMAN","training_data":"The Expression Of Human Equilibrative Nucleoside Transporter 1 (Hent1) Is Associated With Overall Survival In Advanced Biliary Tract Carcinoma (Btc) Treated With Gemcitabine [Introduction] The outcome of patients with unresectable and postoperative recurrent biliary tract carcinoma (BTC) is mostly miserable and most patients are possible candidates for palliative chemotherapy. Gemcitabine is a pyrimidine nucleoside analogue that is commonly used chemotherapeutic agent for advanced BTC. Gemcitabine is transported into the cell mostly by human equilibrative nucleoside transporter 1(hENT1). The hENT1 expression has been demonstrated to play an important role in predicting clinical outcome after gemcitabine chemotherapy for several types of cancer. The aim of the present study was to investigate a predictive marker for good prognosis of gemcitabine chemotherapy for unresectable and postoperative recurrent BTC. [Materials and methods] The analysis was performed on samples from 25 patients with unresectable (6 patients) and postoperative recurrent (19 patients) BTC treated with gemcitabine at the host institute between January 1997 and January 2011. The hENT1 expression levels in tumors were evaluated by immunohistochemistry. The clinical and histopathological variables were analyzed to evaluate predictive values for survival. [Results] Of the 25 tumor specimens, 18 (72%) specimens had positive hNET1 immunostaing, while 7 (28%) specimens were classified as negative. No statistical significant differences were found between the expression of hENT1 and patient characteristics (gender, age, tumor stage, lymph node stage, lymph duct invasion, vascular invasion, perineural invasion). In the univariate analysis, hENT1 expression was significantly correlated with overall survival (OS). The median OS was 15.3 versus 4.2 months, respectively in patients with positive versus negative hENT1 staining (p=0.006). As a result of multivariate analysis, hENT1 expression was useful as a predictive marker for good prognosis with significant difference (p<0.001). [Conclusions] Patients with positive hENT1 expression in BTC have a significantly longer survival after gemcitabine chemotherapy than patients with negative hENT1 expression. Our results suggest that hENT1 expression in advanced BTC patients treated with gemcitabine is a prognostic predictive indicator and is useful to decide gemcitabine chemotherapy. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"aberrant expression vimentin correlates dedifferentiation poor prognosis patients intrahepatic cholangiocarcinoma background study aimed elucidate prognostic value vimentin expression patients intrahepatic cholangiocarcinoma icc patients methods retrospective analysis 21 patients underwent resection icc conducted vimentin expression positive single tumour cells cell clusters showed immunoreactivity vimentin whereas vimentin negative expression defined detectable expression results 21 patients 5 classified tumours vimentin positive expression 16 vimentin negative expression vimentin positive expression frequent tumour specimens poorly differentiated 4 7 57 well moderately differentiated 1 14 7 p 0 025 always seen areas highest histological grade vimentin positive expression affected survival adversely according univariate p 0 010 multivariate analyses relative risk 4 294 p 0 047 conclusion vimentin positive expression correlates dedifferentiation predicts poor survival patients undergoing resection icc pubmed","probabilities":0.962963,"Title":"Aberrant expression of vimentin correlates with dedifferentiation and poor prognosis in patients with intrahepatic cholangiocarcinoma","Abstract":"BACKGROUND: This study aimed to elucidate the prognostic value of vimentin expression in patients with intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: A retrospective analysis of 21 patients who underwent resection for ICC was conducted. Vimentin expression was positive when single tumour cells or cell clusters showed immunoreactivity to vimentin, whereas vimentin-negative expression was defined as no detectable expression. RESULTS: Of the 21 patients, 5 were classified as having tumours with vimentin-positive expression and 16 with vimentin-negative expression. Vimentin-positive expression was more frequent in tumour specimens that were poorly differentiated (4/7; 57%) than in those that were well- or moderately differentiated (1/14; 7%, p=0.025) and was always seen in areas with the highest histological grade. Vimentin-positive expression affected survival adversely, according to univariate (p=0.010) and multivariate analyses (relative risk, 4.294; p=0.047). CONCLUSION: Vimentin-positive expression correlates with dedifferentiation and predicts poor survival in patients undergoing resection for ICC.","Source":"PubMed","category":"HUMAN","training_data":"Aberrant expression of vimentin correlates with dedifferentiation and poor prognosis in patients with intrahepatic cholangiocarcinoma BACKGROUND: This study aimed to elucidate the prognostic value of vimentin expression in patients with intrahepatic cholangiocarcinoma (ICC). PATIENTS AND METHODS: A retrospective analysis of 21 patients who underwent resection for ICC was conducted. Vimentin expression was positive when single tumour cells or cell clusters showed immunoreactivity to vimentin, whereas vimentin-negative expression was defined as no detectable expression. RESULTS: Of the 21 patients, 5 were classified as having tumours with vimentin-positive expression and 16 with vimentin-negative expression. Vimentin-positive expression was more frequent in tumour specimens that were poorly differentiated (4/7; 57%) than in those that were well- or moderately differentiated (1/14; 7%, p=0.025) and was always seen in areas with the highest histological grade. Vimentin-positive expression affected survival adversely, according to univariate (p=0.010) and multivariate analyses (relative risk, 4.294; p=0.047). CONCLUSION: Vimentin-positive expression correlates with dedifferentiation and predicts poor survival in patients undergoing resection for ICC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"clinicopathological features prognosis advanced biliary carcinoma centered cystic duct background whether classify advanced subserosal layer greater invasion biliary carcinoma centered cystic duct bccd gallbladder carcinoma gbc perihilar cholangiocarcinoma phcc remains unclear methods clinicopathological features overall survival os patients advanced bccd examined comparison patients advanced phcc gbc results 290 patients classified 199 phcc 44 gbc 47 bccd patients bccd median 23 months significantly worse os phcc 44 months p 0 030 os patients bccd classified pt3 pt4 american joint committee cancer ajcc classification gbc similar 27 patients pt3 pt4 gbc 23 months p 0 840 patients bccd classified ajcc classification phcc 36 classified pt2 os among patients bccd classified pt2 phcc classification 29 months significantly worse among patients classified pt2 phcc 48 months p 0 040 conclusion findings suggest advanced bccd appropriately classified subtype gbc grow serosa pubmed","probabilities":0.9799733,"Title":"Clinicopathological features and prognosis of advanced biliary carcinoma centered in the cystic duct","Abstract":"BACKGROUND: Whether to classify \"advanced (subserosal layer or greater invasion)\" biliary carcinoma centered in the cystic duct (BCCD) as gallbladder carcinoma (GBC) or perihilar cholangiocarcinoma (PHCC) remains unclear. METHODS: The clinicopathological features and overall survival (OS) of patients with advanced BCCD were examined through a comparison with those of patients with advanced PHCC and with GBC. RESULTS: 290 patients were classified as 199 PHCC, 44 GBC, and 47 BCCD. Patients with BCCD (median, 23 months) had significantly worse OS than those with PHCC (44 months, p = 0.030). OS of patients with BCCD, all of whom were classified as pT3 or pT4 by the American Joint Committee on Cancer (AJCC) classification of GBC, was similar to 27 patients with pT3 or pT4 GBC (23 months, p = 0.840). When the patients with BCCD were classified by the AJCC classification of PHCC, 36 were classified as pT2. OS among the patients with BCCD classified as pT2 by the PHCC classification (29 months) was significantly worse than that among patients classified as pT2 PHCC (48 months, p = 0.040). CONCLUSION: These findings suggest that advanced BCCD is appropriately classified as a subtype of GBC because it can grow through the serosa.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological features and prognosis of advanced biliary carcinoma centered in the cystic duct BACKGROUND: Whether to classify \"advanced (subserosal layer or greater invasion)\" biliary carcinoma centered in the cystic duct (BCCD) as gallbladder carcinoma (GBC) or perihilar cholangiocarcinoma (PHCC) remains unclear. METHODS: The clinicopathological features and overall survival (OS) of patients with advanced BCCD were examined through a comparison with those of patients with advanced PHCC and with GBC. RESULTS: 290 patients were classified as 199 PHCC, 44 GBC, and 47 BCCD. Patients with BCCD (median, 23 months) had significantly worse OS than those with PHCC (44 months, p = 0.030). OS of patients with BCCD, all of whom were classified as pT3 or pT4 by the American Joint Committee on Cancer (AJCC) classification of GBC, was similar to 27 patients with pT3 or pT4 GBC (23 months, p = 0.840). When the patients with BCCD were classified by the AJCC classification of PHCC, 36 were classified as pT2. OS among the patients with BCCD classified as pT2 by the PHCC classification (29 months) was significantly worse than that among patients classified as pT2 PHCC (48 months, p = 0.040). CONCLUSION: These findings suggest that advanced BCCD is appropriately classified as a subtype of GBC because it can grow through the serosa. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival surgery recurrent biliary tract cancer single center experience systematic review literature background recurrent biliary tract cancer chemotherapy standard treatment however efficacy surgery unknown prognostic benefit surgery recurrent biliary tract cancer investigated methods data 206 patients underwent surgery biliary tract cancer 2005 2015 retrospectively analyzed 107 recurrent patients divided two groups surgery n 14 non surgery n 93 groups latter group 45 patients received chemotherapy 48 received best supportive care results total 121 sites recurrence liver common n 41 followed locoregional recurrence n 32 lymph nodes n 18 surgery performed 14 patients recurrence comprising nine patients intrahepatic cholangiocarcinoma three perihilar cholangiocarcinoma one distal cholangiocarcinoma one gallbladder carcinoma survival recurrence significantly better surgery chemotherapy best supportive care 38 vs 5 3 vs 0 3 years 19 vs 5 3 vs 0 5 years p 0 0001 multivariate analysis identified residual status primary tumor hazard ratio 1 58 95 confidence interval 1 00 2 44 p 0 047 time recurrence 1 year hazard ratio 0 62 95 confidence interval 0 39 0 97 p 0 037 surgery recurrence hazard ratio 0 32 95 confidence interval 0 14 0 62 p 0 001 independent prognostic factors conclusions surgery recurrent biliary tract cancer may prolong survival patients time recurrence 1 year pubmed","probabilities":0.9799733,"Title":"Survival of surgery for recurrent biliary tract cancer: a single-center experience and systematic review of literature","Abstract":"BACKGROUND: For recurrent biliary tract cancer, chemotherapy is the standard treatment. However, the efficacy of surgery is unknown. Here, the prognostic benefit of surgery for recurrent biliary tract cancer was investigated. METHODS: Data of 206 patients who underwent surgery for biliary tract cancer between 2005 and 2015 were retrospectively analyzed. Of these, 107 recurrent patients were divided into two groups, surgery (n = 14) and non-surgery (n = 93) groups. In the latter group, 45 patients received chemotherapy and 48 received best supportive care. RESULTS: Of the total 121 sites of recurrence, the liver was the most common (n = 41), followed by locoregional recurrence (n = 32) and lymph nodes (n = 18). Surgery was performed in the 14 patients with recurrence, comprising nine patients with intrahepatic cholangiocarcinoma, three with perihilar cholangiocarcinoma, one with distal cholangiocarcinoma and one with gallbladder carcinoma. Survival after recurrence was significantly better after surgery than after chemotherapy or best supportive care (38% vs. 5.3% vs. 0% at 3 years and 19% vs. 5.3% vs. 0% at 5 years; P < 0.0001). Multivariate analysis identified the residual status of the primary tumor (hazard ratio = 1.58, 95% confidence interval = 1.00-2.44; P = 0.047), time to recurrence ≥1 year (hazard ratio = 0.62, 95% confidence interval = 0.39-0.97; P = 0.037) and surgery for recurrence (hazard ratio = 0.32, 95% confidence interval = 0.14-0.62; P < 0.001) as independent prognostic factors. CONCLUSIONS: Surgery for recurrent biliary tract cancer may prolong survival in patients with time to recurrence ≥1 year.","Source":"PubMed","category":"HUMAN","training_data":"Survival of surgery for recurrent biliary tract cancer: a single-center experience and systematic review of literature BACKGROUND: For recurrent biliary tract cancer, chemotherapy is the standard treatment. However, the efficacy of surgery is unknown. Here, the prognostic benefit of surgery for recurrent biliary tract cancer was investigated. METHODS: Data of 206 patients who underwent surgery for biliary tract cancer between 2005 and 2015 were retrospectively analyzed. Of these, 107 recurrent patients were divided into two groups, surgery (n = 14) and non-surgery (n = 93) groups. In the latter group, 45 patients received chemotherapy and 48 received best supportive care. RESULTS: Of the total 121 sites of recurrence, the liver was the most common (n = 41), followed by locoregional recurrence (n = 32) and lymph nodes (n = 18). Surgery was performed in the 14 patients with recurrence, comprising nine patients with intrahepatic cholangiocarcinoma, three with perihilar cholangiocarcinoma, one with distal cholangiocarcinoma and one with gallbladder carcinoma. Survival after recurrence was significantly better after surgery than after chemotherapy or best supportive care (38% vs. 5.3% vs. 0% at 3 years and 19% vs. 5.3% vs. 0% at 5 years; P < 0.0001). Multivariate analysis identified the residual status of the primary tumor (hazard ratio = 1.58, 95% confidence interval = 1.00-2.44; P = 0.047), time to recurrence ≥1 year (hazard ratio = 0.62, 95% confidence interval = 0.39-0.97; P = 0.037) and surgery for recurrence (hazard ratio = 0.32, 95% confidence interval = 0.14-0.62; P < 0.001) as independent prognostic factors. CONCLUSIONS: Surgery for recurrent biliary tract cancer may prolong survival in patients with time to recurrence ≥1 year. PubMed","prediction_labels":"HUMAN"},{"cleaned":"circulating micrornas biomarkers biliary tract cancers biliary tract cancers btcs group highly aggressive malignant tumors poor prognosis current diagnosis based mainly imaging intraoperative exploration due brush cytology havinga low sensitivity standard markers carcinoembryonic antigen cea carbohydrate 19 9 ca19 9 enough sensitivity specificity used differential diagnosis early stage detection thus better non invasive methods distinguish normal pathological tissue needed micrornas mirnas small single stranded non coding rna molecules 20 22 nucleotides regulate relevant physiological mechanisms also involved carcinogenesis recent studies demonstrated mirnas detectable multiple body fluids showing great stability either free trapped circulating microvesicles exosomes mirnas ideal biomarkers may used screening prognosis biliary tract cancers aiding also clinical decisions different stages cancer treatment review highlights progress analysis circulating mirnas serum plasma bile potential diagnostic prognostic markers btcs pubmed","probabilities":0.7966102,"Title":"Circulating MicroRNAs as Biomarkers in Biliary Tract Cancers","Abstract":"Biliary tract cancers (BTCs) are a group of highly aggressive malignant tumors with a poor prognosis. The current diagnosis is based mainly on imaging and intraoperative exploration due to brush cytology havinga low sensitivity and the standard markers, such as carcinoembryonic antigen (CEA) and carbohydrate 19-9 (CA19-9), not having enough sensitivity nor specificity to be used in a differential diagnosis and early stage detection. Thus, better non-invasive methods that can distinguish between normal and pathological tissue are needed. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules of ~20-22 nucleotides that regulate relevant physiological mechanisms and can also be involved in carcinogenesis. Recent studies have demonstrated that miRNAs are detectable in multiple body fluids, showing great stability, either free or trapped in circulating microvesicles, such as exosomes. miRNAs are ideal biomarkers that may be used in screening and prognosis in biliary tract cancers, aiding also in the clinical decisions at different stages of cancer treatment. This review highlights the progress in the analysis of circulating miRNAs in serum, plasma and bile as potential diagnostic and prognostic markers of BTCs.","Source":"PubMed","category":"HUMAN","training_data":"Circulating MicroRNAs as Biomarkers in Biliary Tract Cancers Biliary tract cancers (BTCs) are a group of highly aggressive malignant tumors with a poor prognosis. The current diagnosis is based mainly on imaging and intraoperative exploration due to brush cytology havinga low sensitivity and the standard markers, such as carcinoembryonic antigen (CEA) and carbohydrate 19-9 (CA19-9), not having enough sensitivity nor specificity to be used in a differential diagnosis and early stage detection. Thus, better non-invasive methods that can distinguish between normal and pathological tissue are needed. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules of ~20-22 nucleotides that regulate relevant physiological mechanisms and can also be involved in carcinogenesis. Recent studies have demonstrated that miRNAs are detectable in multiple body fluids, showing great stability, either free or trapped in circulating microvesicles, such as exosomes. miRNAs are ideal biomarkers that may be used in screening and prognosis in biliary tract cancers, aiding also in the clinical decisions at different stages of cancer treatment. This review highlights the progress in the analysis of circulating miRNAs in serum, plasma and bile as potential diagnostic and prognostic markers of BTCs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"novel invaginated roux en y hepaticojejunostomy mesohepatectomy hilar cholangiocarcinoma bismuth corlette type iii major liver resection bismuth corlette type iii hilar cholangiocarcinoma hc reportedly associated high morbidity mortality limited liver resection mesohepatectomy resection tumorinvolved bile ducts way improve surgical outcomes hc however biliary tract reconstruction mesohepatectomy poses great technical challenge established new invaginated hepaticojejunostomy ihj biliary tract reconstruction especially multiple hepatic duct openings study aims evaluate safety effectiveness ihj total 156 patients bismuth corlette type iii hc underwent radical resection 2001 2012 113 patients underwent mesohepatectomy 43 underwent hemihepatectomy extended hemi heatectomy ihj adopted 109 patients traditional hepaticojejunostomy thj 47 patients short term surgical comes two groups compared 48 pigs equally divided two groups one underwent ihj another group underwent thj healing process ihj pathologically studied clinical data patients undergoing ihj thj shown table 1 death within 30 postoperative days groups postoperative morbidity ihj group signi cantly lower thj group animal experiment revealed cross section connecting enteric cavity gradually covered regenerated enterocytes leaving small part covered regenerated biliary epithelial cells ihj mesohepatectomy bismuth corlette type iii hc simple effective procedure signi cant less morbidity animal study con rmed ihj excellently healed without problem google scholar","probabilities":0.9799733,"Title":"A Novel Invaginated Roux-En-Y Hepaticojejunostomy After Mesohepatectomy For Hilar Cholangiocarcinoma Of Bismuth-Corlette Type Iii","Abstract":"Major liver resection for Bismuth-Corlette type III hilar cholangiocarcinoma (HC) is reportedly associated with high morbidity and mortality. Limited liver resection such as mesohepatectomy with resection of tumorinvolved bile ducts could be a way to improve surgical outcomes of HC. However, biliary tract reconstruction after mesohepatectomy poses a great technical challenge. We established a new invaginated hepaticojejunostomy (IHJ) for biliary tract reconstruction especially for multiple hepatic duct openings. This study aims to evaluate the safety and effectiveness of IHJ. A total of 156 patients with Bismuth-Corlette type III HC underwent radical resection from 2001 to 2012. 113 patients underwent mesohepatectomy, and 43 underwent hemihepatectomy or extended hemi-heatectomy. IHJ was adopted in 109 patients, and traditional hepaticojejunostomy (THJ) in 47 patients. Short-term surgical out\ncomes between two groups were compared. 48 pigs were equally divided into two groups. One underwent IHJ, and another group underwent THJ. Healing process of IHJ was pathologically studied. The clinical data of the patients undergoing IHJ and THJ were shown in Table 1. No death within 30 postoperative days in the both groups. The postoperative morbidity in IHJ group is significantly lower than that in THJ group. Animal experiment revealed that the cross section connecting to the enteric cavity was gradually covered by regenerated enterocytes, leaving a small part covered by regenerated biliary epithelial cells. IHJ after mesohepatectomy for Bismuth-Corlette type III HC is a simple, effective procedure with significant less morbidity. Animal study confirmed that IHJ was excellently healed without any problem.","Source":"Google Scholar","category":"ANIMAL","training_data":"A Novel Invaginated Roux-En-Y Hepaticojejunostomy After Mesohepatectomy For Hilar Cholangiocarcinoma Of Bismuth-Corlette Type Iii Major liver resection for Bismuth-Corlette type III hilar cholangiocarcinoma (HC) is reportedly associated with high morbidity and mortality. Limited liver resection such as mesohepatectomy with resection of tumorinvolved bile ducts could be a way to improve surgical outcomes of HC. However, biliary tract reconstruction after mesohepatectomy poses a great technical challenge. We established a new invaginated hepaticojejunostomy (IHJ) for biliary tract reconstruction especially for multiple hepatic duct openings. This study aims to evaluate the safety and effectiveness of IHJ. A total of 156 patients with Bismuth-Corlette type III HC underwent radical resection from 2001 to 2012. 113 patients underwent mesohepatectomy, and 43 underwent hemihepatectomy or extended hemi-heatectomy. IHJ was adopted in 109 patients, and traditional hepaticojejunostomy (THJ) in 47 patients. Short-term surgical out\ncomes between two groups were compared. 48 pigs were equally divided into two groups. One underwent IHJ, and another group underwent THJ. Healing process of IHJ was pathologically studied. The clinical data of the patients undergoing IHJ and THJ were shown in Table 1. No death within 30 postoperative days in the both groups. The postoperative morbidity in IHJ group is significantly lower than that in THJ group. Animal experiment revealed that the cross section connecting to the enteric cavity was gradually covered by regenerated enterocytes, leaving a small part covered by regenerated biliary epithelial cells. IHJ after mesohepatectomy for Bismuth-Corlette type III HC is a simple, effective procedure with significant less morbidity. Animal study confirmed that IHJ was excellently healed without any problem. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"long non coding rna anril affects cell proliferation migration epigenetically regulating angptl4 errfi1 expression cholangiocarcinoma abstract available google scholar","probabilities":0.9467213,"Title":"Long Non-Coding Rna Anril Affects Cell Proliferation And Migration By Epigenetically Regulating Angptl4 And Errfi1 Expression In Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"ANIMAL","training_data":"Long Non-Coding Rna Anril Affects Cell Proliferation And Migration By Epigenetically Regulating Angptl4 And Errfi1 Expression In Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"bcl 2 degradation additional pro apoptotic effect polo like kinase inhibition cholangiocarcinoma cells aim examine influence apoptotic mechanisms following inhibition polo like kinases therapeutically approach cholangiocellular cancer treatment methods cholangiocarcinomas chemotherapy resistant due mechanisms preventing tumor cell death investigated effect cisplatin cholangiocellular carcinoma cca cell lines kmch 1 mz ch 1 polo like kinases plk important regulators cell cycle inhibition discussed potential therapy plk inhibition regulate apoptotic mediators cells treated plk inhibitor bi6727 volasertib cisplatin combination compounds cell viability assessed mtt apoptosis measured dapi staining caspase 3 7 assay western blot qrt pcr used measure expression levels apoptosis related molecules bax bcl 2 results cell viability cca cell lines kmch 1 mz ch 1 reduced treatment conditions compared vehicle treated cells co treatment bi6727 cisplatin even enhance cytotoxic effect cisplatin single treatment thus co treatment cisplatin bi6727 slightly enhance cytotoxic effect cisplatin cell lines whereas evidence increased apoptosis induction solely mz ch 1 compared kmch 1 moreover plk inhibition decreases protein levels bcl 2 effect reversed proteasomal degradation inhibitor mg 132 contrast protein levels bax found altered plk inhibition findings indicate cytotoxic effects cisplatin mz ch 1 cells enhanced cotreatment bi6727 conclusion conclusion bi6727 treatment sensitize cca cells cisplatin induced apoptosis proteasomal bcl 2 degradation additional pro apoptotic effect stn","probabilities":0.9467213,"Title":"Bcl-2 Degradation Is An Additional Pro-Apoptotic Effect Of Polo-Like Kinase Inhibition In Cholangiocarcinoma Cells","Abstract":"Aim: To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment. \r\n\r\n Methods: As most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators. Here, cells were treated with PLK inhibitor BI6727 (Volasertib), Cisplatin, and in combination of both compounds. Cell viability was assessed by MTT; apoptosis was measured by DAPI staining and caspase-3/-7 assay. Western blot and qRT-PCR were used to measure expression levels of apoptosis-related molecules Bax and Bcl-2. \r\n\r\n Results: The cell viability in the CCA cell lines KMCH-1 and Mz-Ch-1 was reduced in all treatment conditions compared to vehicle-treated cells. Co-treatment with BI6727 and cisplatin could even enhance the cytotoxic effect of cisplatin single treatment. Thus, co-treatment of cisplatin with BI6727 could slightly enhance the cytotoxic effect of the cisplatin in both cell lines whereas there was evidence of increased apoptosis induction solely in Mz-Ch-1 as compared to KMCH-1. Moreover, PLK inhibition decreases protein levels of Bcl-2; an effect that can be reversed by the proteasomal degradation inhibitor MG-132. In contrast, protein levels of Bax were not found to be altered by PLK inhibition. These findings indicate that cytotoxic effects of Cisplatin in Mz-Ch-1 cells can be enhanced by cotreatment with BI6727. \r\n\r\n Conclusion: In conclusion, BI6727 treatment can sensitize CCA cells to cisplatin-induced apoptosis with proteasomal Bcl-2 degradation as an additional pro-apoptotic effect.","Source":"STN","category":"ANIMAL","training_data":"Bcl-2 Degradation Is An Additional Pro-Apoptotic Effect Of Polo-Like Kinase Inhibition In Cholangiocarcinoma Cells Aim: To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeutically approach for cholangiocellular cancer treatment. \r\n\r\n Methods: As most cholangiocarcinomas are chemotherapy-resistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma (CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases (PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators. Here, cells were treated with PLK inhibitor BI6727 (Volasertib), Cisplatin, and in combination of both compounds. Cell viability was assessed by MTT; apoptosis was measured by DAPI staining and caspase-3/-7 assay. Western blot and qRT-PCR were used to measure expression levels of apoptosis-related molecules Bax and Bcl-2. \r\n\r\n Results: The cell viability in the CCA cell lines KMCH-1 and Mz-Ch-1 was reduced in all treatment conditions compared to vehicle-treated cells. Co-treatment with BI6727 and cisplatin could even enhance the cytotoxic effect of cisplatin single treatment. Thus, co-treatment of cisplatin with BI6727 could slightly enhance the cytotoxic effect of the cisplatin in both cell lines whereas there was evidence of increased apoptosis induction solely in Mz-Ch-1 as compared to KMCH-1. Moreover, PLK inhibition decreases protein levels of Bcl-2; an effect that can be reversed by the proteasomal degradation inhibitor MG-132. In contrast, protein levels of Bax were not found to be altered by PLK inhibition. These findings indicate that cytotoxic effects of Cisplatin in Mz-Ch-1 cells can be enhanced by cotreatment with BI6727. \r\n\r\n Conclusion: In conclusion, BI6727 treatment can sensitize CCA cells to cisplatin-induced apoptosis with proteasomal Bcl-2 degradation as an additional pro-apoptotic effect. STN","prediction_labels":"ANIMAL"},{"cleaned":"cholecystectomy risk cholangiocarcinoma cca meta analysis observational studies abstract available google scholar","probabilities":0.9799733,"Title":"Cholecystectomy And Risk Of Cholangiocarcinoma (Cca): A Meta-Analysis Of Observational Studies","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Cholecystectomy And Risk Of Cholangiocarcinoma (Cca): A Meta-Analysis Of Observational Studies Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"selective histology cholecystectomy specimens justified background gallbladder cancer gbc rare common malignancy biliary tract dismal prognosis early diagnosis surgical treatment gbc offers chance long term survival despite advances radiological imaging early diagnosis gbc still rarely achieved without histopathology hospital routine histologic examination resected gallbladder specimens standard practice study seeks define whether selective histologic examination gallbladder specimens based preoperative imaging intraoperative findings justified materials methods september 2008 september 2013 histopathology reports gallbladder specimens elective cholecystectomy retrospectively analyzed single surgical unit preoperative imaging intraoperative findings histology notes analyzed cases results 14 369 60 female 40 male patients undergoing cholecystectomy gbc found 46 cases 0 32 one fifth 10 46 gbc patients presented acute cholecutitis ac 10 ac patients coexisted gbc harbored significantly inflamed gallbladders 83 49 ac patients judged significant inflammation carcinoma situ early gbc t1a t1b accounted 61 cases two patients tis t1a respectively show suspicious lesion preoperative intraoperative findings remaining cases 44 46 gbc suspected either preoperative imaging intraoperative findings conclusions almost cases invasive gbc show macroscopic abnormalities following examination simple procedure full dissection inspection palpation gallbladder patient early gbcs missed macroscopic examination still receive appropriate treatment cholecystectomy alone gallbladder sent histology macroscopic examination raises suspicion selective policy cost effective appear compromise patients outcome pubmed","probabilities":0.9799733,"Title":"Selective histology of cholecystectomy specimens--is it justified?","Abstract":"BACKGROUND: Gallbladder cancer (GBC) is rare but the most common malignancy of biliary tract with a dismal prognosis. The early diagnosis and surgical treatment of GBC offers the only chance of long-term survival. Despite advances in radiological imaging, early diagnosis of GBC is still rarely achieved without histopathology. In our hospital, routine histologic examination of all resected gallbladder specimens has been standard practice. This study seeks to define whether selective histologic examination for gallbladder specimens based on preoperative imaging or intraoperative findings is justified. MATERIALS AND METHODS: From September 2008-September 2013, all histopathology reports of gallbladder specimens after elective cholecystectomy were retrospectively analyzed in a single surgical unit. Preoperative imaging, intraoperative findings, and histology notes were analyzed in all cases. RESULTS: Out of 14,369 (60% female and 40% male) patients undergoing cholecystectomy, GBC was found in only 46 cases (0.32%). More than one fifth (10/46) of GBC patients presented with acute cholecutitis (AC). All 10 AC patients coexisted with GBC harbored \"significantly inflamed' gallbladders, and about 83.49% AC patients were judged with \"significant inflammation.\" Carcinoma in situ and early GBC (T1a, T1b) accounted for 61% of all cases. Only two patients with Tis and T1a respectively did not show suspicious lesion on preoperative and intraoperative findings, but for the remaining cases (44/46), GBC was suspected either by preoperative imaging and/or intraoperative findings. CONCLUSIONS: Almost all cases of invasive GBC will show macroscopic abnormalities following examination by a simple procedure-a full dissection, inspection, and palpation of the gallbladder. Any patient with early GBCs \"missed\" on macroscopic examination can still receive the appropriate treatment by the cholecystectomy alone. The gallbladder should be sent for histology only if macroscopic examination raises suspicion. This selective policy is more cost-effective, and does not appear to compromise patients outcome.","Source":"PubMed","category":"HUMAN","training_data":"Selective histology of cholecystectomy specimens--is it justified? BACKGROUND: Gallbladder cancer (GBC) is rare but the most common malignancy of biliary tract with a dismal prognosis. The early diagnosis and surgical treatment of GBC offers the only chance of long-term survival. Despite advances in radiological imaging, early diagnosis of GBC is still rarely achieved without histopathology. In our hospital, routine histologic examination of all resected gallbladder specimens has been standard practice. This study seeks to define whether selective histologic examination for gallbladder specimens based on preoperative imaging or intraoperative findings is justified. MATERIALS AND METHODS: From September 2008-September 2013, all histopathology reports of gallbladder specimens after elective cholecystectomy were retrospectively analyzed in a single surgical unit. Preoperative imaging, intraoperative findings, and histology notes were analyzed in all cases. RESULTS: Out of 14,369 (60% female and 40% male) patients undergoing cholecystectomy, GBC was found in only 46 cases (0.32%). More than one fifth (10/46) of GBC patients presented with acute cholecutitis (AC). All 10 AC patients coexisted with GBC harbored \"significantly inflamed' gallbladders, and about 83.49% AC patients were judged with \"significant inflammation.\" Carcinoma in situ and early GBC (T1a, T1b) accounted for 61% of all cases. Only two patients with Tis and T1a respectively did not show suspicious lesion on preoperative and intraoperative findings, but for the remaining cases (44/46), GBC was suspected either by preoperative imaging and/or intraoperative findings. CONCLUSIONS: Almost all cases of invasive GBC will show macroscopic abnormalities following examination by a simple procedure-a full dissection, inspection, and palpation of the gallbladder. Any patient with early GBCs \"missed\" on macroscopic examination can still receive the appropriate treatment by the cholecystectomy alone. The gallbladder should be sent for histology only if macroscopic examination raises suspicion. This selective policy is more cost-effective, and does not appear to compromise patients outcome. PubMed","prediction_labels":"HUMAN"},{"cleaned":"aberrant glycosylation cholangiocarcinoma demonstrated lectin histochemistry cholangiocarcinoma cca aggressive malignant tumor difficult diagnose early stage reliable cca specific markers available present patients diagnosed late clinical presentation many tumors aberrant glycans participate various steps pathogenesis progression study investigated aberrant glycosylation cca tissues using lectin histochemistry allow associations specific glycans clinicopathological features patients investigated purpose 14 lectins specific 5 main glycan structures used screening nine lectins showed positive staining hepatocyte sand stromal cells liver tissues whereas three lectins swga sja uea negative lectin binding hepatocytes normal bile duct epithelia exhibited positive staining cca swga selected evaluation d glcnac n glycoconjugate expressions 44 cca tissues found swga specific glycans aberrantly expressed along cca development level expression varied histological types highly expressed papillary well differentiated types significantly reduced poorly differentiated lesions specific associations swga specific glycoconjugate expression clinicopathological features overall survival patients apparent cohort study pubmed","probabilities":0.9285714,"Title":"Aberrant glycosylation in cholangiocarcinoma demonstrated by lectin-histochemistry","Abstract":"Cholangiocarcinoma (CCA) is an aggressive malignant tumor which is difficult to diagnose at an early stage. Because no reliable CCA specific markers are available at present, most patients are diagnosed after late clinical presentation. In many tumors, aberrant glycans participate in various steps of pathogenesis and progression. In this study, we investigated aberrant glycosylation in CCA tissues using lectin histochemistry to allow associations of specific glycans with clinicopathological features of the patients to be investigated. For this purpose, 14 lectins specific to 5 main glycan structures were used for screening. Nine lectins showed positive staining in hepatocyte sand stromal cells in liver tissues whereas three lectins, sWGA, SJA and UEA-I, had negative lectin binding to hepatocytes and normal bile duct epithelia but exhibited positive staining with CCA. sWGA was selected for further evaluation of (β-D-GlcNAc)n-glycoconjugate expressions in 44 CCA tissues. We found that sWGA- specific glycans were aberrantly expressed along with CCA development and the level of expression varied with histological types. It was highly expressed in papillary and well-differentiated types but was significantly reduced in poorly-differentiated lesions. Specific associations of sWGA-specific glycoconjugate expression with clinicopathological features or overall survival of patients were not apparent in this cohort study.","Source":"PubMed","category":"ANIMAL","training_data":"Aberrant glycosylation in cholangiocarcinoma demonstrated by lectin-histochemistry Cholangiocarcinoma (CCA) is an aggressive malignant tumor which is difficult to diagnose at an early stage. Because no reliable CCA specific markers are available at present, most patients are diagnosed after late clinical presentation. In many tumors, aberrant glycans participate in various steps of pathogenesis and progression. In this study, we investigated aberrant glycosylation in CCA tissues using lectin histochemistry to allow associations of specific glycans with clinicopathological features of the patients to be investigated. For this purpose, 14 lectins specific to 5 main glycan structures were used for screening. Nine lectins showed positive staining in hepatocyte sand stromal cells in liver tissues whereas three lectins, sWGA, SJA and UEA-I, had negative lectin binding to hepatocytes and normal bile duct epithelia but exhibited positive staining with CCA. sWGA was selected for further evaluation of (β-D-GlcNAc)n-glycoconjugate expressions in 44 CCA tissues. We found that sWGA- specific glycans were aberrantly expressed along with CCA development and the level of expression varied with histological types. It was highly expressed in papillary and well-differentiated types but was significantly reduced in poorly-differentiated lesions. Specific associations of sWGA-specific glycoconjugate expression with clinicopathological features or overall survival of patients were not apparent in this cohort study. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"prognostic value decreased ndrg1 expression patients digestive system cancers meta analysis background digestive system cancers recognized associated high morbidity mortality generally accepted n myc downstream regulated gene 1 ndrg1 aberrantly overexpressed downregulated digestive system cancers prognostic value remains controversial accordingly herein conducted meta analysis explore whether ndrg1 expression correlated overall survival os clinicopathological characteristics patients digestive system cancers methods systematically searched pubmed embase web science eligible studies june 6 2017 19 publications 21 studies included results pooled results showed low ndrg1 expression significantly associated worse os colorectal cancer pooled hr 1 67 95 ci 1 22 2 28 p 001 pancreatic cancer pooled hr 1 87 95 ci 1 3 5 p 0001 moreover relationships low ndrg1 expression higher os ratio patients liver cancer pooled hr 0 44 95 ci 0 32 0 62 p 009 gallbladder cancer pooled hr 0 56 95 ci 0 23 1 38 p 01 observed nevertheless significant association observed low ndrg1 expression os gastric cancer pooled hr 0 81 95 ci 0 45 1 43 p 46 esophageal cancer pooled hr 0 76 95 ci 0 26 2 24 p 62 conclusion prognostic significance ndrg1 expression varies according cancer type patients dscs considering several limitations existed meta analysis studies required assess prognostic value ndrg1 expression patients dscs relevant mechanisms pubmed","probabilities":0.9799733,"Title":"The prognostic value of decreased NDRG1 expression in patients with digestive system cancers: A meta-analysis","Abstract":"BACKGROUND: Digestive system cancers are recognized as associated with high morbidity and mortality. It is generally accepted that N-myc downstream-regulated gene 1 (NDRG1) is aberrantly overexpressed or downregulated in digestive system cancers, and its prognostic value remains controversial. Accordingly, we herein conducted a meta-analysis to explore whether NDRG1 expression is correlated with overall survival (OS) and clinicopathological characteristics of patients with digestive system cancers. METHODS: We systematically searched PubMed, EMBASE, and Web of Science for eligible studies up to June 6, 2017. In all, 19 publications with 21 studies, were included. RESULTS: The pooled results showed that low NDRG1 expression was significantly associated with worse OS in colorectal cancer (pooled HR = 1.67, 95% CI: 1.22-2.28, P < .001) and pancreatic cancer (pooled HR = 1.87, 95% CI: 1-3.5, P < .0001). Moreover, the relationships between low NDRG1 expression and higher OS ratio of patients with liver cancer (pooled HR = 0.44, 95% CI: 0.32-0.62, P = .009) and gallbladder cancer (pooled HR = 0.56, 95% CI: 0.23-1.38, P = .01) were observed. Nevertheless, no significant association was observed between low NDRG1 expression and OS in gastric cancer (pooled HR = 0.81, 95% CI: 0.45-1.43, P = .46) or esophageal cancer (pooled HR = 0.76, 95% CI: 0.26-2.24, P = .62). CONCLUSION: The prognostic significance of NDRG1 expression varies according to cancer type in patients with DSCs. Considering that several limitations existed in this meta-analysis, more studies are required to further assess the prognostic value of NDRG1 expression in patients with DSCs and relevant mechanisms.","Source":"PubMed","category":"HUMAN","training_data":"The prognostic value of decreased NDRG1 expression in patients with digestive system cancers: A meta-analysis BACKGROUND: Digestive system cancers are recognized as associated with high morbidity and mortality. It is generally accepted that N-myc downstream-regulated gene 1 (NDRG1) is aberrantly overexpressed or downregulated in digestive system cancers, and its prognostic value remains controversial. Accordingly, we herein conducted a meta-analysis to explore whether NDRG1 expression is correlated with overall survival (OS) and clinicopathological characteristics of patients with digestive system cancers. METHODS: We systematically searched PubMed, EMBASE, and Web of Science for eligible studies up to June 6, 2017. In all, 19 publications with 21 studies, were included. RESULTS: The pooled results showed that low NDRG1 expression was significantly associated with worse OS in colorectal cancer (pooled HR = 1.67, 95% CI: 1.22-2.28, P < .001) and pancreatic cancer (pooled HR = 1.87, 95% CI: 1-3.5, P < .0001). Moreover, the relationships between low NDRG1 expression and higher OS ratio of patients with liver cancer (pooled HR = 0.44, 95% CI: 0.32-0.62, P = .009) and gallbladder cancer (pooled HR = 0.56, 95% CI: 0.23-1.38, P = .01) were observed. Nevertheless, no significant association was observed between low NDRG1 expression and OS in gastric cancer (pooled HR = 0.81, 95% CI: 0.45-1.43, P = .46) or esophageal cancer (pooled HR = 0.76, 95% CI: 0.26-2.24, P = .62). CONCLUSION: The prognostic significance of NDRG1 expression varies according to cancer type in patients with DSCs. Considering that several limitations existed in this meta-analysis, more studies are required to further assess the prognostic value of NDRG1 expression in patients with DSCs and relevant mechanisms. PubMed","prediction_labels":"HUMAN"},{"cleaned":"comparison competing lymph node staging schemes resectable biliary cancer background new classifications lymph node ln staging recently proposed improve upon uicc ajcc n category staging convention ratio based systems logarithmic odds lodds scores two families novel competing staging systems compared uicc ajcc staging 5 ratio lodds systems predicting overall survival os patients resected gastric cancer methods using large population based dataset identified 12 184 nonmetastatic resectable gastric cancer patients 1988 2004 compared subject uicc ajcc n stage five novel staging schemes analyzed os method comparison metric log rank chi squared statistic larger chi squared statistics indicate improvements n stage discrimination results median os 2 1 years 95 ci 2 0 2 2 years median patient follow surviving patients 8 3 years range 1 month 22 years although 5 staging systems either comparable superior uicc ajcc convention ln ratio method outperformed others n stage discrimination based log rank tests os trend independent number lns examined conclusions novel ln staging methods higher degree discrimination utility uicc ajcc n convention methods may role reducing prognostic impact ln count variability systems assessed ln ratio system assigns greater risk attribution cases 16 lns best classification method predict os patients resectable gastric cancer stn","probabilities":0.9799733,"Title":"A Comparison Of Competing Lymph Node Staging Schemes In Resectable Biliary Cancer","Abstract":"Background: New classifications for lymph node (LN) staging have recently been proposed to improve upon the UICC/AJCC N category staging convention. Ratio-based systems and logarithmic odds (LODDS) scores are two families of novel competing staging systems. We compared UICC/AJCC staging with 5 ratio and LODDS systems in predicting overall survival (OS) in patients with resected gastric cancer. \r\n\r\n Methods: Using a large population-based dataset, we identified 12,184 nonmetastatic resectable gastric cancer patients between 1988 and 2004. We compared each subject's UICC/AJCC N stage with five novel staging schemes. We analyzed the OS for each method. Our comparison metric was the log-rank Chi squared statistic; larger Chi squared statistics indicate improvements in N stage discrimination. \r\n\r\n Results: Median OS was 2.1 years (95 % CI 2.0-2.2 years), while median patient follow-up for surviving patients was 8.3 years (range, 1 month-22 years). Although all 5 staging systems were either comparable or superior to the UICC/AJCC convention, a LN ratio method outperformed others in N stage discrimination based on log-rank tests for OS. This trend was independent of the number of LNs examined. \r\n\r\n Conclusions: Novel LN staging methods have a higher degree of discrimination utility than the UICC/AJCC N convention. These methods may have a role in reducing the prognostic impact of LN count variability. Of the systems assessed, the LN ratio system that assigns greater risk attribution to cases with <16 LNs was the best classification method to predict OS in patients with resectable gastric cancer.","Source":"STN","category":"HUMAN","training_data":"A Comparison Of Competing Lymph Node Staging Schemes In Resectable Biliary Cancer Background: New classifications for lymph node (LN) staging have recently been proposed to improve upon the UICC/AJCC N category staging convention. Ratio-based systems and logarithmic odds (LODDS) scores are two families of novel competing staging systems. We compared UICC/AJCC staging with 5 ratio and LODDS systems in predicting overall survival (OS) in patients with resected gastric cancer. \r\n\r\n Methods: Using a large population-based dataset, we identified 12,184 nonmetastatic resectable gastric cancer patients between 1988 and 2004. We compared each subject's UICC/AJCC N stage with five novel staging schemes. We analyzed the OS for each method. Our comparison metric was the log-rank Chi squared statistic; larger Chi squared statistics indicate improvements in N stage discrimination. \r\n\r\n Results: Median OS was 2.1 years (95 % CI 2.0-2.2 years), while median patient follow-up for surviving patients was 8.3 years (range, 1 month-22 years). Although all 5 staging systems were either comparable or superior to the UICC/AJCC convention, a LN ratio method outperformed others in N stage discrimination based on log-rank tests for OS. This trend was independent of the number of LNs examined. \r\n\r\n Conclusions: Novel LN staging methods have a higher degree of discrimination utility than the UICC/AJCC N convention. These methods may have a role in reducing the prognostic impact of LN count variability. Of the systems assessed, the LN ratio system that assigns greater risk attribution to cases with <16 LNs was the best classification method to predict OS in patients with resectable gastric cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"prognostic factors selection patients eligible second line chemotherapy advanced biliary tract cancer background efficacy second line chemotherapy ct2 failure first line chemotherapy ct1 advanced biliary tract cancer btc established investigated favorable prognostic factors ct2 determine patients expected benefit ct2 methods total 168 patients treated chemotherapy institution january 2003 december 2012 retrospectively reviewed 50 patients received ct2 patients treated various chemotherapeutic combinations ct1 ct2 results median overall survival os patients received ct2 10 2 5 5 months respectively good performance status ps serum albumin level 3 5 g dl metastasis 1 organ independent prognostic factors affected os patients received ct2 patients 1 metastastic organ good ps serum albumin level 3 5 g dl beginning ct2 demonstrated prolonged survival compared patients exhibit 3 factors 9 5 vs 4 3 months p 0 005 conclusions ct2 considered patients advanced btc especially 1 metastatic organ remain generally good medical condition failure ct1 pubmed","probabilities":0.9799733,"Title":"Prognostic Factors for the Selection of Patients Eligible for Second-Line Chemotherapy in Advanced Biliary Tract Cancer","Abstract":"BACKGROUND: The efficacy of second-line chemotherapy (CT2) after the failure of first-line chemotherapy (CT1) for advanced biliary tract cancer (BTC) has not been established. We investigated the favorable prognostic factors for CT2 to determine which patients could be expected to benefit from CT2. METHODS: From a total of 168 patients who were treated with chemotherapy at our institution between January 2003 and December 2012, we retrospectively reviewed 50 patients who received CT2. Patients were treated with various chemotherapeutic combinations as CT1 and CT2. RESULts: The median overall survival (OS) of patients who received and CT2 was 10.2 and 5.5 months, respectively. Good performance status (PS), a serum albumin level >3.5 g/dl and metastasis to only 1 organ were independent prognostic factors that affected the OS of the patients who received CT2. Patients who had only 1 metastastic organ, a good PS and a serum albumin level >3.5 g/dl at the beginning of CT2 demonstrated prolonged survival compared to patients who did not exhibit these 3 factors (9.5 vs. 4.3 months, p < 0.005). CONCLUSIONS: CT2 should be considered for patients with advanced BTC, especially for those who have only 1 metastatic organ and remain in generally good medical condition after the failure of CT1.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic Factors for the Selection of Patients Eligible for Second-Line Chemotherapy in Advanced Biliary Tract Cancer BACKGROUND: The efficacy of second-line chemotherapy (CT2) after the failure of first-line chemotherapy (CT1) for advanced biliary tract cancer (BTC) has not been established. We investigated the favorable prognostic factors for CT2 to determine which patients could be expected to benefit from CT2. METHODS: From a total of 168 patients who were treated with chemotherapy at our institution between January 2003 and December 2012, we retrospectively reviewed 50 patients who received CT2. Patients were treated with various chemotherapeutic combinations as CT1 and CT2. RESULts: The median overall survival (OS) of patients who received and CT2 was 10.2 and 5.5 months, respectively. Good performance status (PS), a serum albumin level >3.5 g/dl and metastasis to only 1 organ were independent prognostic factors that affected the OS of the patients who received CT2. Patients who had only 1 metastastic organ, a good PS and a serum albumin level >3.5 g/dl at the beginning of CT2 demonstrated prolonged survival compared to patients who did not exhibit these 3 factors (9.5 vs. 4.3 months, p < 0.005). CONCLUSIONS: CT2 should be considered for patients with advanced BTC, especially for those who have only 1 metastatic organ and remain in generally good medical condition after the failure of CT1. PubMed","prediction_labels":"HUMAN"},{"cleaned":"taurolithocholic acid promotes intrahepatic cholangiocarcinoma cell growth via muscarinic acetylcholine receptor egfr erk1 2 signaling pathway cholangiocarcinoma cca malignant cancer biliary tract occurrence associated chronic cholestasis causes elevation bile acids liver bile duct present study aimed investigate role mechanistic effect bile acids cca cell growth intrahepatic cca cell lines rmcca 1 hucca 1 treated bile acids metabolites determine growth promoting effect cell viability cell cycle analysis edu incorporation assays conducted intracellular signaling proteins detected western immunoblotting among eleven forms bile acids metabolites taurolithocholic acid tlca concentration dependently 1 40 m increased cell viability rmcca 1 hucca 1 cells cell cycle analysis showed induction cells phase edu incorporation assay revealed induction dna synthesis tlca treated rmcca 1 cells moreover tlca increased phosphorylation egfr erk 1 2 also increased expression cyclin d1 rmcca 1 cells furthermore tlca induced rmcca 1 cell growth inhibited atropine non selective muscarinic acetylcholine receptor machr antagonist ag 1478 specific egfr inhibitor u 0126 specific mek 1 2 inhibitor results suggest tlca induces cca cell growth via machr egfr ekr1 2 signaling pathway moreover functional presence cholinergic system plays certain role tlca induced cca cell growth stn","probabilities":0.9467213,"Title":"Taurolithocholic Acid Promotes Intrahepatic Cholangiocarcinoma Cell Growth Via Muscarinic Acetylcholine Receptor And Egfr/Erk1/2 Signaling Pathway","Abstract":"Cholangiocarcinoma (CCA) is a malignant cancer of the biliary tract and its occurrence is associated with chronic cholestasis which causes an elevation of bile acids in the liver and bile duct. The present study aimed to investigate the role and mechanistic effect of bile acids on the CCA cell growth. Intrahepatic CCA cell lines, RMCCA-1 and HuCCA-1, were treated with bile acids and their metabolites to determine the growth promoting effect. Cell viability, cell cycle analysis, EdU incorporation assays were conducted. Intracellular signaling proteins were detected by western immunoblotting. Among eleven forms of bile acids and their metabolites, only taurolithocholic acid (TLCA) concentration dependently (1-40 µM) increased the cell viability of RMCCA-1, but not HuCCA-1 cells. The cell cycle analysis showed induction of cells in the S phase and the EdU incorporation assay revealed induction of DNA synthesis in the TLCA-treated RMCCA-1 cells. Moreover, TLCA increased the phosphorylation of EGFR, ERK 1/2 and also increased the expression of cyclin D1 in RMCCA-1 cells. Furthermore, TLCA-induced RMCCA-1 cell growth could be inhibited by atropine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, AG 1478, a specific EGFR inhibitor, or U 0126, a specific MEK 1/2 inhibitor. These results suggest that TLCA induces CCA cell growth via mAChR and EGFR/EKR1/2 signaling pathway. Moreover, the functional presence of cholinergic system plays a certain role in TLCA-induced CCA cell growth.","Source":"STN","category":"ANIMAL","training_data":"Taurolithocholic Acid Promotes Intrahepatic Cholangiocarcinoma Cell Growth Via Muscarinic Acetylcholine Receptor And Egfr/Erk1/2 Signaling Pathway Cholangiocarcinoma (CCA) is a malignant cancer of the biliary tract and its occurrence is associated with chronic cholestasis which causes an elevation of bile acids in the liver and bile duct. The present study aimed to investigate the role and mechanistic effect of bile acids on the CCA cell growth. Intrahepatic CCA cell lines, RMCCA-1 and HuCCA-1, were treated with bile acids and their metabolites to determine the growth promoting effect. Cell viability, cell cycle analysis, EdU incorporation assays were conducted. Intracellular signaling proteins were detected by western immunoblotting. Among eleven forms of bile acids and their metabolites, only taurolithocholic acid (TLCA) concentration dependently (1-40 µM) increased the cell viability of RMCCA-1, but not HuCCA-1 cells. The cell cycle analysis showed induction of cells in the S phase and the EdU incorporation assay revealed induction of DNA synthesis in the TLCA-treated RMCCA-1 cells. Moreover, TLCA increased the phosphorylation of EGFR, ERK 1/2 and also increased the expression of cyclin D1 in RMCCA-1 cells. Furthermore, TLCA-induced RMCCA-1 cell growth could be inhibited by atropine, a non-selective muscarinic acetylcholine receptor (mAChR) antagonist, AG 1478, a specific EGFR inhibitor, or U 0126, a specific MEK 1/2 inhibitor. These results suggest that TLCA induces CCA cell growth via mAChR and EGFR/EKR1/2 signaling pathway. Moreover, the functional presence of cholinergic system plays a certain role in TLCA-induced CCA cell growth. STN","prediction_labels":"ANIMAL"},{"cleaned":"efficacy plastic stents replaced regular intervals unresectable hilar cholangiocarcinoma introduction malignant biliary obstruction hilar cholangiocarcinoma often amenable surgical intervention biliary stenting used improve cholestatic symptoms overall quality life center practice place plastic stents across hilar strictures replace regular intervals lieu uncovered metal stents believe allows better management episodes cholangitis occur allows management evolving hilar strictures progress objective study evaluate efficacy regularly placing plastic stents management malignant hilar obstruction placed single endoscopist methods retrospective review conducted april 2012 december 2016 tertiary care center patients included study unresectable malignant hilar cholangiocarcinoma underwent plastic stent placement management stents exchanged regularly scheduled intervals 10 12 weeks unless symptoms suggestive cholangitis patients one procedure subsequently elected pursue treatment modalities excluded technical success defined passage stent across stricture flow contrast across stent clinical success defined improvement total bilirubin less 75 within one month results 19 patients included study patients bismuth classification iv table 1 median survival 372 days interquartile range iqr 172 516 days average 5 26 procedures performed per patient 2 06 stents placed per procedure patients average procedure every 2 4 months 10 patients 53 required urgent procedure cholangitis routinely scheduled stent exchange 10 patients 58 procedures urgent procedures cholangitis complication none procedures complicated perforation bleeding pancreatitis 3 patients passed away one procedure stage iv bismuth classification iv median survival procedure 47 days 2 3 bilateral stents placed 100 technical success improvement total bilirubin discharge one patient 50 improvement 3 days one passed home home hospice one moved away passed one passed unknown etiology discussion regular plastic stent exchange malignant hilar obstruction secondary cholangiocarcinoma effective increasing long term survival 3 months intervention 4 months unilateral metal stents 11 months bilateral metal stents future studies performed confirm findings google scholar","probabilities":0.9799733,"Title":"Efficacy Of Plastic Stents Replaced At Regular Intervals In Unresectable Hilar Cholangiocarcinoma","Abstract":"Introduction\nMalignant biliary obstruction from hilar cholangiocarcinoma are often not amenable to surgical intervention. Biliary stenting can be used to improve cholestatic symptoms and overall quality of life. At our center, the practice is to place plastic stents across hilar strictures and replace them at regular intervals in lieu of uncovered metal stents. We believe this allows for better management of episodes of cholangitis when they occur, and allows management of evolving hilar strictures if they progress. The objective of this study was to evaluate the efficacy of regularly placing plastic stents in management of malignant hilar obstruction placed by a single endoscopist.\nMethods\nA retrospective review was conducted between April 2012 to December 2016 at a tertiary care center. Patients included in the study had unresectable malignant hilar cholangiocarcinoma and underwent plastic stent placement for management. Stents were exchanged at regularly scheduled intervals of 10-12 weeks unless they had symptoms suggestive of cholangitis. Patients who only had one procedure and then subsequently elected to pursue other treatment modalities were excluded. Technical success was defined as passage of stent across a stricture with flow of contrast across stent. Clinical success was defined as improvement in total bilirubin to less than 75% within one month.\nResults\n19 patients were included in the study. All patients had Bismuth classification IV (Table 1). Median survival was 372 days with interquartile range (IQR) of 172 and 516 days. On average, 5.26 procedures were performed per patient with 2.06 stents placed per procedure. Patients on average had a procedure every 2.4 months. 10 patients (53%) required an urgent procedure for cholangitis before the routinely scheduled stent exchange; in these 10 patients, 58% of their procedures were urgent procedures. Cholangitis was the only complication; none of the procedures were complicated by perforation, bleeding, or pancreatitis.\nThere were 3 patients who passed away after one procedure. All were Stage IV with Bismuth classification IV. Median survival from the procedure was 47 days. 2/3 had bilateral stents placed. There was 100% technical success, and all of them had improvement in total bilirubin on discharge, with one patient having a 50% improvement after 3 days. One passed at home under home hospice, one moved away and passed, and one passed of unknown etiology.\nDiscussion\nRegular plastic stent exchange for malignant hilar obstruction secondary to cholangiocarcinoma is effective in increasing long term survival from 3 months with no intervention, 4 months with unilateral metal stents, and 11 months with bilateral metal stents. Future studies should be performed to confirm our findings.","Source":"Google Scholar","category":"HUMAN","training_data":"Efficacy Of Plastic Stents Replaced At Regular Intervals In Unresectable Hilar Cholangiocarcinoma Introduction\nMalignant biliary obstruction from hilar cholangiocarcinoma are often not amenable to surgical intervention. Biliary stenting can be used to improve cholestatic symptoms and overall quality of life. At our center, the practice is to place plastic stents across hilar strictures and replace them at regular intervals in lieu of uncovered metal stents. We believe this allows for better management of episodes of cholangitis when they occur, and allows management of evolving hilar strictures if they progress. The objective of this study was to evaluate the efficacy of regularly placing plastic stents in management of malignant hilar obstruction placed by a single endoscopist.\nMethods\nA retrospective review was conducted between April 2012 to December 2016 at a tertiary care center. Patients included in the study had unresectable malignant hilar cholangiocarcinoma and underwent plastic stent placement for management. Stents were exchanged at regularly scheduled intervals of 10-12 weeks unless they had symptoms suggestive of cholangitis. Patients who only had one procedure and then subsequently elected to pursue other treatment modalities were excluded. Technical success was defined as passage of stent across a stricture with flow of contrast across stent. Clinical success was defined as improvement in total bilirubin to less than 75% within one month.\nResults\n19 patients were included in the study. All patients had Bismuth classification IV (Table 1). Median survival was 372 days with interquartile range (IQR) of 172 and 516 days. On average, 5.26 procedures were performed per patient with 2.06 stents placed per procedure. Patients on average had a procedure every 2.4 months. 10 patients (53%) required an urgent procedure for cholangitis before the routinely scheduled stent exchange; in these 10 patients, 58% of their procedures were urgent procedures. Cholangitis was the only complication; none of the procedures were complicated by perforation, bleeding, or pancreatitis.\nThere were 3 patients who passed away after one procedure. All were Stage IV with Bismuth classification IV. Median survival from the procedure was 47 days. 2/3 had bilateral stents placed. There was 100% technical success, and all of them had improvement in total bilirubin on discharge, with one patient having a 50% improvement after 3 days. One passed at home under home hospice, one moved away and passed, and one passed of unknown etiology.\nDiscussion\nRegular plastic stent exchange for malignant hilar obstruction secondary to cholangiocarcinoma is effective in increasing long term survival from 3 months with no intervention, 4 months with unilateral metal stents, and 11 months with bilateral metal stents. Future studies should be performed to confirm our findings. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"epithelial mesenchymal transition ampullary cancer background ampullary cancer relatively rare form cancer usually treated pancreatoduodenectomy followed adjuvant therapy intestinal subtype associated markedly improved prognosis resection present cell lines available vitro studies ampullary cancer collectively characterized methods characterize five ampullary cancer cell lines subtype maker expression epithelial mesenchymal transition emt features growth invasion drug sensitivity response cancer associated fibroblast conditioned medium caf cm results basis emt features subtype marker expression growth invasion drug sensitivity three types cell lines distinguished mesenchymal like pancreatobiliary like intestinal like heterogeneous effects cell lines response caf cm different growth rates induction emt markers well suppression intestinal differentiation markers observed addition proteomic analysis showed clear difference intestinal like cell line cell lines conclusion available ampac cell lines seem reflect poorly differentiated pancreatobiliary mesenchymal like phenotype consistent origin suggest appropriate cell line model intestinal like ampac snu869 others seem reflect aggressive ampac subtypes stn","probabilities":0.9467213,"Title":"Epithelial-Mesenchymal Transition In Ampullary Cancer","Abstract":"Background: Ampullary cancer is a relatively rare form of cancer and usually treated by pancreatoduodenectomy, followed by adjuvant therapy. The intestinal subtype is associated with markedly improved prognosis after resection. At present, only few cell lines are available for in vitro studies of ampullary cancer and they have not been collectively characterized. \r\n\r\n Methods: We characterize five ampullary cancer cell lines by subtype maker expression, epithelial-mesenchymal transition (EMT) features, growth and invasion, drug sensitivity and response to cancer-associated fibroblast conditioned medium (CAF-CM). \r\n\r\n Results: On the basis of EMT features, subtype marker expression, growth, invasion and drug sensitivity three types of cell lines could be distinguished: mesenchymal-like, pancreatobiliary-like and intestinal-like. Heterogeneous effects from the cell lines in response to CAF-CM, such as different growth rates, induction of EMT markers as well as suppression of intestinal differentiation markers were observed. In addition, proteomic analysis showed a clear difference in intestinal-like cell line from other cell lines. \r\n\r\n Conclusion: Most of the available AMPAC cell lines seem to reflect a poorly differentiated pancreatobiliary or mesenchymal-like phenotype, which is consistent to their origin. We suggest that the most appropriate cell line model for intestinal-like AMPAC is the SNU869, while others seem to reflect aggressive AMPAC subtypes.","Source":"STN","category":"ANIMAL","training_data":"Epithelial-Mesenchymal Transition In Ampullary Cancer Background: Ampullary cancer is a relatively rare form of cancer and usually treated by pancreatoduodenectomy, followed by adjuvant therapy. The intestinal subtype is associated with markedly improved prognosis after resection. At present, only few cell lines are available for in vitro studies of ampullary cancer and they have not been collectively characterized. \r\n\r\n Methods: We characterize five ampullary cancer cell lines by subtype maker expression, epithelial-mesenchymal transition (EMT) features, growth and invasion, drug sensitivity and response to cancer-associated fibroblast conditioned medium (CAF-CM). \r\n\r\n Results: On the basis of EMT features, subtype marker expression, growth, invasion and drug sensitivity three types of cell lines could be distinguished: mesenchymal-like, pancreatobiliary-like and intestinal-like. Heterogeneous effects from the cell lines in response to CAF-CM, such as different growth rates, induction of EMT markers as well as suppression of intestinal differentiation markers were observed. In addition, proteomic analysis showed a clear difference in intestinal-like cell line from other cell lines. \r\n\r\n Conclusion: Most of the available AMPAC cell lines seem to reflect a poorly differentiated pancreatobiliary or mesenchymal-like phenotype, which is consistent to their origin. We suggest that the most appropriate cell line model for intestinal-like AMPAC is the SNU869, while others seem to reflect aggressive AMPAC subtypes. STN","prediction_labels":"ANIMAL"},{"cleaned":"biliary tract carcinomas retrospective analysis first line chemotherapy based platinium compounds second line based 5 fluororacil abstract available google scholar","probabilities":0.9799733,"Title":"Biliary Tract Carcinomas - A Retrospective Analysis Of First Line Chemotherapy Based On Platinium Compounds And Second Line Based On 5 Fluororacil","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Biliary Tract Carcinomas - A Retrospective Analysis Of First Line Chemotherapy Based On Platinium Compounds And Second Line Based On 5 Fluororacil Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"endoscopic stenting hilar cholangiocarcinoma efficacy unilateral bilateral placement plastic metal stents retrospective review 480 patients background endoscopic biliary drainage hilar cholangiocarcinoma controversial respect optimal types stents extent drainage study evaluated endoscopic palliation patients hilar cholangiocarcinoma using self expandable metallic stents sems plastic stents ps also compared unilateral bilateral stent placement according bismuth classification methods data 480 patients receiving endoscopic biliary drainage hilar cholangiocarcinoma september 1995 december 2010 retrospectively reviewed evaluate following outcome parameters technical success ts functional success fs early late complications stent patency survival patients followed stent insertion death stent occlusion patients divided 3 groups according bismuth classification group 1 type group 2 type ii group 3 type iii results initial stent insertion successful 450 93 8 patients ts achieved 204 88 3 patients treated ps 246 98 8 patients palliated sems p 0 001 intention treat itt analysis fs patients treated sems 97 9 significantly higher patients treated ps 84 8 p 0 001 late complications occurred 115 56 4 patients treated ps 60 24 4 patients treated sems p 0 001 median duration stent patency weeks w follows 20 w patients palliated ps 27 w patients treated sems p 0 0001 group 2 median duration ps patency 17 w 18 w unilateral bilateral placement respectively p 0 0004 median duration sems patency 24 w 29 w unilateral bilateral placement respectively p 0 0001 multivariate analysis using poisson regression showed sems placement b 0 48 p 0 01 bilateral deployment b 0 24 p 0 01 independent prognostic factors associated stent patency conclusions sems insertion palliation hilar cholangiocarcinoma offers higher technical clinical success rates itt analysis well lower complication rates superior cumulative stent patency compared ps placement bismuth classifications cumulative patency bilateral sems ps stents significantly higher unilateral sems ps stents lower occlusion rates bismuth ii patients pubmed","probabilities":0.9799733,"Title":"Endoscopic stenting for hilar cholangiocarcinoma: efficacy of unilateral and bilateral placement of plastic and metal stents in a retrospective review of 480 patients","Abstract":"BACKGROUND: Endoscopic biliary drainage of hilar cholangiocarcinoma is controversial with respect to the optimal types of stents and the extent of drainage. This study evaluated endoscopic palliation in patients with hilar cholangiocarcinoma using self-expandable metallic stents (SEMS) and plastic stents (PS).We also compared unilateral and bilateral stent placement according to the Bismuth classification. METHODS: Data on 480 patients receiving endoscopic biliary drainage for hilar cholangiocarcinoma between September 1995 and December 2010 were retrospectively reviewed to evaluate the following outcome parameters: technical success (TS), functional success (FS), early and late complications, stent patency and survival. Patients were followed from stent insertion until death or stent occlusion. Patients were divided into 3 groups according to the Bismuth classification (Group 1, type I; Group 2, type II; Group 3, type ≥ III). RESULTS: The initial stent insertion was successful in 450 (93.8%) patients. TS was achieved in 204 (88.3%) patients treated with PS and in 246 (98.8%) patients palliated with SEMS (p < 0.001). In the intention-to-treat (ITT) analysis, the FS in patients treated with SEMS (97.9%) was significantly higher than in patients treated with PS (84.8%) (p < 0.001). Late complications occurred in 115 (56.4%) patients treated with PS and 60 (24.4%) patients treated with SEMS (p < 0.001). The median duration of stent patency in weeks (w) were as follows: 20 w in patients palliated with PS and 27 w in patients treated with SEMS (p < 0.0001). In Group 2, the median duration of PS patency was 17 w and 18 w for unilateral and bilateral placement, respectively (p = 0.0004); the median duration of SEMS patency was 24 w and 29 w for unilateral and bilateral placement, respectively (p < 0.0001). Multivariate analysis using the Poisson regression showed that SEMS placement (B = 0.48; P < 0.01) and bilateral deployment (B = 0.24; P < 0.01) were the only independent prognostic factors associated with stent patency. CONCLUSIONS: SEMS insertion for the palliation of hilar cholangiocarcinoma offers higher technical and clinical success rates in the ITT analysis as well as lower complication rates and a superior cumulative stent patency when compared with PS placement in all Bismuth classifications. The cumulative patency of bilateral SEMS or PS stents was significantly higher than that of unilateral SEMS or PS stents, with lower occlusion rates in Bismuth II patients.","Source":"PubMed","category":"HUMAN","training_data":"Endoscopic stenting for hilar cholangiocarcinoma: efficacy of unilateral and bilateral placement of plastic and metal stents in a retrospective review of 480 patients BACKGROUND: Endoscopic biliary drainage of hilar cholangiocarcinoma is controversial with respect to the optimal types of stents and the extent of drainage. This study evaluated endoscopic palliation in patients with hilar cholangiocarcinoma using self-expandable metallic stents (SEMS) and plastic stents (PS).We also compared unilateral and bilateral stent placement according to the Bismuth classification. METHODS: Data on 480 patients receiving endoscopic biliary drainage for hilar cholangiocarcinoma between September 1995 and December 2010 were retrospectively reviewed to evaluate the following outcome parameters: technical success (TS), functional success (FS), early and late complications, stent patency and survival. Patients were followed from stent insertion until death or stent occlusion. Patients were divided into 3 groups according to the Bismuth classification (Group 1, type I; Group 2, type II; Group 3, type ≥ III). RESULTS: The initial stent insertion was successful in 450 (93.8%) patients. TS was achieved in 204 (88.3%) patients treated with PS and in 246 (98.8%) patients palliated with SEMS (p < 0.001). In the intention-to-treat (ITT) analysis, the FS in patients treated with SEMS (97.9%) was significantly higher than in patients treated with PS (84.8%) (p < 0.001). Late complications occurred in 115 (56.4%) patients treated with PS and 60 (24.4%) patients treated with SEMS (p < 0.001). The median duration of stent patency in weeks (w) were as follows: 20 w in patients palliated with PS and 27 w in patients treated with SEMS (p < 0.0001). In Group 2, the median duration of PS patency was 17 w and 18 w for unilateral and bilateral placement, respectively (p = 0.0004); the median duration of SEMS patency was 24 w and 29 w for unilateral and bilateral placement, respectively (p < 0.0001). Multivariate analysis using the Poisson regression showed that SEMS placement (B = 0.48; P < 0.01) and bilateral deployment (B = 0.24; P < 0.01) were the only independent prognostic factors associated with stent patency. CONCLUSIONS: SEMS insertion for the palliation of hilar cholangiocarcinoma offers higher technical and clinical success rates in the ITT analysis as well as lower complication rates and a superior cumulative stent patency when compared with PS placement in all Bismuth classifications. The cumulative patency of bilateral SEMS or PS stents was significantly higher than that of unilateral SEMS or PS stents, with lower occlusion rates in Bismuth II patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"tlr4 expression normal gallbladder chronic cholecystitis gallbladder carcinoma background aims chronic inflammation risk factor gallbladder carcinoma molecular mechanisms linking inflammation gallbladder carcinogenesis incompletely understood toll like receptors involved inflammatory response play important role innate immune system initiating directing immune response pathogens tested hypothesis tlr4 participated development gallbladder carcinoma investigating expression tlr4 chronic cholecystitis gallbladder carcinoma normal gallbladder methodology expression tlr4 30 specimens chronic calculous cholecystitis 13 specimens gallbladder adenocarcinoma 10 specimens normal gallbladder tissue determined immunohistochemistry western blotting analysis quantitative rt pcr results showed tlr4 mostly localized glandular luminal epithelium gallbladder tlr4 expression lower gallbladder carcinoma tissue chronic cholecystitis normal gallbladder tissue whereas difference chronic cholecystitis tissue normal gallbladder tissue statistically significant conclusions expression tlr4 may closely associated course gallbladder carcinoma stn","probabilities":0.7966102,"Title":"Tlr4 Expression In Normal Gallbladder Chronic Cholecystitis And Gallbladder Carcinoma","Abstract":"Background/aims: Chronic inflammation is a risk factor for gallbladder carcinoma. The molecular mechanisms linking inflammation and gallbladder carcinogenesis are incompletely understood. Toll-like receptors are involved in inflammatory response and play an important role in the innate immune system by initiating and directing immune response to pathogens. We tested the hypothesis that TLR4 participated in the development of gallbladder carcinoma through investigating the expression of TLR4 in chronic cholecystitis, gallbladder carcinoma and normal gallbladder. \r\n\r\n Methodology: The expression of TLR4 in 30 specimens of chronic calculous cholecystitis, 13 specimens of gallbladder adenocarcinoma and 10 specimens of normal gallbladder tissue was determined by immunohistochemistry, western blotting analysis and quantitative RT-PCR. \r\n\r\n Results: We showed that TLR4 was mostly localized to the glandular and luminal epithelium of gallbladder. TLR4 expression was lower in gallbladder carcinoma tissue than in chronic cholecystitis and normal gallbladder tissue, whereas the difference between chronic cholecystitis tissue and normal gallbladder tissue was not statistically significant. \r\n\r\n Conclusions: The expression of TLR4 may be closely associated with the course of gallbladder carcinoma.","Source":"STN","category":"HUMAN","training_data":"Tlr4 Expression In Normal Gallbladder Chronic Cholecystitis And Gallbladder Carcinoma Background/aims: Chronic inflammation is a risk factor for gallbladder carcinoma. The molecular mechanisms linking inflammation and gallbladder carcinogenesis are incompletely understood. Toll-like receptors are involved in inflammatory response and play an important role in the innate immune system by initiating and directing immune response to pathogens. We tested the hypothesis that TLR4 participated in the development of gallbladder carcinoma through investigating the expression of TLR4 in chronic cholecystitis, gallbladder carcinoma and normal gallbladder. \r\n\r\n Methodology: The expression of TLR4 in 30 specimens of chronic calculous cholecystitis, 13 specimens of gallbladder adenocarcinoma and 10 specimens of normal gallbladder tissue was determined by immunohistochemistry, western blotting analysis and quantitative RT-PCR. \r\n\r\n Results: We showed that TLR4 was mostly localized to the glandular and luminal epithelium of gallbladder. TLR4 expression was lower in gallbladder carcinoma tissue than in chronic cholecystitis and normal gallbladder tissue, whereas the difference between chronic cholecystitis tissue and normal gallbladder tissue was not statistically significant. \r\n\r\n Conclusions: The expression of TLR4 may be closely associated with the course of gallbladder carcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"carcinoma situ gallbladder seer database perspective background previous analysis carcinoma situ cis gallbladder gb reported nci surveillance epidemiology end results seer program demonstrated 5 10 yr survival estimates 100 70 respectively experience high incidence regions early gallbladder carcinoma also includes minimally invasive mucosa con ned carcinoma good prognosis 10 yr survival 90 gbs sampled entirely possibility advanced carcinoma carefully ruled design 685 cases recorded cis gb seer database 1973 2010 survival information analyzed addition observed survival relative survival relevant older population also calculated based expected survival general population demographics cases additional designation adenoma papillary villous regarded possibly representing tumoral forms cis adenoma associated intracholecystic papillary neoplasm associated grouped tumoral results 80 patients white 69 female almost half 49 70 yrs old observed survival 91 1 yr 80 3 yr 72 5 yr 53 10 yr corresponding 1 3 5 10 yr estimates relative survival 94 89 87 79 respectively survivals generally slightly higher tumoral cases compared casesincludes cases known gender type info conclusions cases recorded situ carcinoma gb seer database mostly elderly females 10 yr survival 79 worse expected early gallbladder carcinoma data high risk regions 10 yr survival 90 difference likely attributable sampling underdiagnosis gbs cis submitted entirely high risk regions us particular deaths within 1 year likely represent underdiagnosed higher stage carcinomas deaths longer f u likely represent true cis cases may re ect eld defect effect phenomenon biliary tract tumoral cis gb may slightly better prognosis imperative pathologists examine gbs entirely rule advanced carcinomas clinicians place patients long term f u google scholar","probabilities":0.9799733,"Title":"Carcinoma In-Situ Of The Gallbladder: The Seer Database Perspective","Abstract":"Background: A previous analysis of carcinoma “in-situ” (CIS) of gallbladder (GB) reported to the NCI’s Surveillance Epidemiology End Results (SEER) program demonstrated 5- and 10-yr survival estimates of 100% and 70%, respectively. In our experience from high-incidence regions, early-gallbladder carcinoma, which also includes minimally invasive mucosa-confi ned carcinoma has a very good prognosis with 10-yr survival of 90%, if the GBs are sampled entirely and the possibility of a more advanced carcinoma has been carefully ruled out. Design: 685 cases recorded as CIS of GB in the SEER database, 1973-2010, with survival information, were analyzed. In addition to observed survival, relative survival, which is more relevant to older population, was also calculated based on the expected survival in the general population with the same demographics. Cases with additional designation of “adenoma”, “papillary” or “villous” were regarded as possibly representing tumoral forms of CIS (adenoma-associated or intracholecystic papillary neoplasm-associated) and grouped as “tumoral”. Results: 80% of the patients were white, 69% were female, and almost half (49%) were≥ 70 yrs old. Observed survival was 91% at 1-yr, 80% at 3-yr, 72% at 5-yr, 53% at 10-yr. The corresponding 1-, 3-, 5-, 10-yr estimates for relative survival were 94%, 89%, 87% and 79%, respectively. Survivals were generally slightly higher for “tumoral” cases compared to “fl at” casesIncludes only cases with known gender & type info Conclusions: Cases recorded as “in-situ” carcinoma of GB in the SEER database are mostly elderly females. The 10-yr survival of 79% is worse than what would be expected from the early-gallbladder carcinoma data from high-risk regions (10-yr survival, 90%). This difference is likely attributable to under-sampling or underdiagnosis (GBs with CIS are submitted entirely in high-risk regions but not in the US). In particular, deaths within 1 year likely represent underdiagnosed higher-stage carcinomas. Of the deaths in longer F/U, some likely represent the true CIS cases, and as such may refl ect a fi eld-defect/effect phenomenon in the biliary tract. Tumoral CIS of GB may have slightly better prognosis. It is imperative for pathologists to examine GBs entirely to rule out advanced carcinomas, and for clinicians to place these patients in long-term F/U.","Source":"Google Scholar","category":"HUMAN","training_data":"Carcinoma In-Situ Of The Gallbladder: The Seer Database Perspective Background: A previous analysis of carcinoma “in-situ” (CIS) of gallbladder (GB) reported to the NCI’s Surveillance Epidemiology End Results (SEER) program demonstrated 5- and 10-yr survival estimates of 100% and 70%, respectively. In our experience from high-incidence regions, early-gallbladder carcinoma, which also includes minimally invasive mucosa-confi ned carcinoma has a very good prognosis with 10-yr survival of 90%, if the GBs are sampled entirely and the possibility of a more advanced carcinoma has been carefully ruled out. Design: 685 cases recorded as CIS of GB in the SEER database, 1973-2010, with survival information, were analyzed. In addition to observed survival, relative survival, which is more relevant to older population, was also calculated based on the expected survival in the general population with the same demographics. Cases with additional designation of “adenoma”, “papillary” or “villous” were regarded as possibly representing tumoral forms of CIS (adenoma-associated or intracholecystic papillary neoplasm-associated) and grouped as “tumoral”. Results: 80% of the patients were white, 69% were female, and almost half (49%) were≥ 70 yrs old. Observed survival was 91% at 1-yr, 80% at 3-yr, 72% at 5-yr, 53% at 10-yr. The corresponding 1-, 3-, 5-, 10-yr estimates for relative survival were 94%, 89%, 87% and 79%, respectively. Survivals were generally slightly higher for “tumoral” cases compared to “fl at” casesIncludes only cases with known gender & type info Conclusions: Cases recorded as “in-situ” carcinoma of GB in the SEER database are mostly elderly females. The 10-yr survival of 79% is worse than what would be expected from the early-gallbladder carcinoma data from high-risk regions (10-yr survival, 90%). This difference is likely attributable to under-sampling or underdiagnosis (GBs with CIS are submitted entirely in high-risk regions but not in the US). In particular, deaths within 1 year likely represent underdiagnosed higher-stage carcinomas. Of the deaths in longer F/U, some likely represent the true CIS cases, and as such may refl ect a fi eld-defect/effect phenomenon in the biliary tract. Tumoral CIS of GB may have slightly better prognosis. It is imperative for pathologists to examine GBs entirely to rule out advanced carcinomas, and for clinicians to place these patients in long-term F/U. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"clinical significance pathologic subtype curatively resected ampulla vater cancer background ampullary cancer considered better prognosis cancers distal bile duct pancreas recent publications emphasize prognostic importance histologic differentiation intestinal pancreatobiliary types ampullary cancer aims study identify factors affect recurrence curative resection investigate differences clinicopathologic features two pathologic subtypes patients methods medical records patients underwent pancreatoduodenectomy ampullary carcinoma february 1995 march 2009 institute retrospectively reviewed one hundred four patients underwent curative resection ampullary carcinoma enrolled study one pathologist reviewed pathologic reports histopathologic findings data clinicopathologic factors disease free overall survival analyzed results 3 5 year disease free survival rates 104 study subjects 62 2 57 7 respectively overall survival rates 69 4 60 1 respectively multivariate analysis showed advanced stage p 0 049 presence lymph node metastasis p 0 003 poor differentiation p 0 039 pancreatobiliary type p 0 022 significantly increased risk recurrence furthermore pancreatobiliary type found associated advanced stage p 0 009 regional lymph node metastasis p 0 007 perineural invasion p 0 026 intestinal type addition pathologic subtype analysis showed carcinoembryonic antigen cea level lymph node metastasis important predictors recurrence patients intestinal p 0 013 pancreatobiliary types respectively p 0 003 conclusions advanced stage nodal metastasis poor differentiation pancreaticobiliary type found independent predictors recurrence curative resection ampullary carcinoma multivariate analysis addition pancreatobiliary type tended present advanced stage frequently regional lymph node involvement perineural invasion intestinal type furthermore cea level lymph node metastasis found independent predictors recurrence intestinal pancreatobiliary types respectively pubmed","probabilities":0.9799733,"Title":"Clinical significance of pathologic subtype in curatively resected ampulla of vater cancer","Abstract":"BACKGROUND: Ampullary cancer is considered to have a better prognosis than cancers of the distal bile duct and pancreas, and recent publications emphasize the prognostic importance of the histologic differentiation of the intestinal and pancreatobiliary types of ampullary cancer. The aims of this study were to identify those factors that affect recurrence after curative resection and to investigate differences between the clinicopathologic features of these two pathologic subtypes. PATIENTS AND METHODS: The medical records of patients that underwent pancreatoduodenectomy for ampullary carcinoma from February 1995 to March 2009 at our institute were retrospectively reviewed. One hundred and four patients that underwent curative resection for ampullary carcinoma were enrolled in this study. One pathologist reviewed all pathologic reports and histopathologic findings. Data on clinicopathologic factors and disease free and overall survival were analyzed. RESULTS: The 3- and 5-year disease free survival rates of the 104 study subjects were 62.2% and 57.7%, respectively, and overall survival rates were 69.4% and 60.1%, respectively. Multivariate analysis showed that an advanced T stage (P = 0.049), the presence of lymph node metastasis (P = 0.003), poor differentiation (P = 0.039), and the pancreatobiliary type (P = 0.022) significantly increased the risk of recurrence. Furthermore, the pancreatobiliary type was found to be more associated with an advanced T stage (P = 0.009), regional lymph node metastasis (P = 0.007), and perineural invasion (P = 0.026) than the intestinal type. In addition, pathologic subtype analysis showed that Carcinoembryonic antigen (CEA) level and lymph node metastasis were important predictors of recurrence in patients with the intestinal (P = 0.013) and pancreatobiliary types, respectively (P = 0.003). CONCLUSIONS: An advanced T stage, nodal metastasis, poor differentiation, and the pancreaticobiliary type were found to be independent predictors of recurrence after curative resection of ampullary carcinoma by multivariate analysis. In addition, the pancreatobiliary type tended to present in a more advanced T stage and more frequently with regional lymph node involvement and perineural invasion than the intestinal type. Furthermore, CEA level and lymph node metastasis were found to be independent predictors of recurrence for the intestinal and pancreatobiliary types, respectively.","Source":"PubMed","category":"HUMAN","training_data":"Clinical significance of pathologic subtype in curatively resected ampulla of vater cancer BACKGROUND: Ampullary cancer is considered to have a better prognosis than cancers of the distal bile duct and pancreas, and recent publications emphasize the prognostic importance of the histologic differentiation of the intestinal and pancreatobiliary types of ampullary cancer. The aims of this study were to identify those factors that affect recurrence after curative resection and to investigate differences between the clinicopathologic features of these two pathologic subtypes. PATIENTS AND METHODS: The medical records of patients that underwent pancreatoduodenectomy for ampullary carcinoma from February 1995 to March 2009 at our institute were retrospectively reviewed. One hundred and four patients that underwent curative resection for ampullary carcinoma were enrolled in this study. One pathologist reviewed all pathologic reports and histopathologic findings. Data on clinicopathologic factors and disease free and overall survival were analyzed. RESULTS: The 3- and 5-year disease free survival rates of the 104 study subjects were 62.2% and 57.7%, respectively, and overall survival rates were 69.4% and 60.1%, respectively. Multivariate analysis showed that an advanced T stage (P = 0.049), the presence of lymph node metastasis (P = 0.003), poor differentiation (P = 0.039), and the pancreatobiliary type (P = 0.022) significantly increased the risk of recurrence. Furthermore, the pancreatobiliary type was found to be more associated with an advanced T stage (P = 0.009), regional lymph node metastasis (P = 0.007), and perineural invasion (P = 0.026) than the intestinal type. In addition, pathologic subtype analysis showed that Carcinoembryonic antigen (CEA) level and lymph node metastasis were important predictors of recurrence in patients with the intestinal (P = 0.013) and pancreatobiliary types, respectively (P = 0.003). CONCLUSIONS: An advanced T stage, nodal metastasis, poor differentiation, and the pancreaticobiliary type were found to be independent predictors of recurrence after curative resection of ampullary carcinoma by multivariate analysis. In addition, the pancreatobiliary type tended to present in a more advanced T stage and more frequently with regional lymph node involvement and perineural invasion than the intestinal type. Furthermore, CEA level and lymph node metastasis were found to be independent predictors of recurrence for the intestinal and pancreatobiliary types, respectively. PubMed","prediction_labels":"HUMAN"},{"cleaned":"impact preoperative biliary drainage surgical outcomes periampullary hilar malignancy single center experience role preoperative biliary drainage pbd periampullary hilar malignancy still controversial retrospectively studied consecutive 144 patients 92 periampullary 52 hilar malignancy undergoing surgical resection evaluate effects pbd surgical outcomes rate pbd 59 56 postoperative complications developed 27 19 periampullary hilar malignancy respectively risk factors postoperative complications overweight odds ratio 7 6 depression 8 5 distal malignancy american society anesthesiologists score 3 6 6 depression 13 8 portal vein embolization 6 1 hilar malignancy pbd associated postoperative complications reinterventions pbd necessary 43 27 distal hilar biliary obstruction conclusion pbd pancreatobiliary surgery associated postoperative complications improvement pbd necessary given high rate reinterventions pubmed","probabilities":0.9799733,"Title":"Impact of Preoperative Biliary Drainage on Surgical Outcomes in Periampullary and Hilar Malignancy: A Single-Center Experience","Abstract":"The role of preoperative biliary drainage (PBD) for periampullary and hilar malignancy is still controversial. We retrospectively studied consecutive 144 patients (92 periampullary and 52 hilar malignancy) undergoing surgical resection to evaluate the effects of PBD on surgical outcomes. The rate of PBD was 59% and 56%, and postoperative complications developed in 27% and 19% in periampullary and hilar malignancy, respectively. Risk factors for postoperative complications were overweight [odds ratio (OR), 7.6] and depression (OR, 8.5) in distal malignancy and American society of anesthesiologists score of 3 (OR, 6.6), depression (OR, 13.8), and portal vein embolization (OR, 6.1) in hilar malignancy. PBD was not associated with postoperative complications but reinterventions for PBD were necessary in 43% and 27% in distal and hilar biliary obstruction. In conclusion, PBD in pancreatobiliary surgery was not associated with postoperative complications, but the improvement of PBD is necessary given the high rate of reinterventions.","Source":"PubMed","category":"HUMAN","training_data":"Impact of Preoperative Biliary Drainage on Surgical Outcomes in Periampullary and Hilar Malignancy: A Single-Center Experience The role of preoperative biliary drainage (PBD) for periampullary and hilar malignancy is still controversial. We retrospectively studied consecutive 144 patients (92 periampullary and 52 hilar malignancy) undergoing surgical resection to evaluate the effects of PBD on surgical outcomes. The rate of PBD was 59% and 56%, and postoperative complications developed in 27% and 19% in periampullary and hilar malignancy, respectively. Risk factors for postoperative complications were overweight [odds ratio (OR), 7.6] and depression (OR, 8.5) in distal malignancy and American society of anesthesiologists score of 3 (OR, 6.6), depression (OR, 13.8), and portal vein embolization (OR, 6.1) in hilar malignancy. PBD was not associated with postoperative complications but reinterventions for PBD were necessary in 43% and 27% in distal and hilar biliary obstruction. In conclusion, PBD in pancreatobiliary surgery was not associated with postoperative complications, but the improvement of PBD is necessary given the high rate of reinterventions. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatitis b virus hepatitis c virus play different prognostic roles intrahepatic cholangiocarcinoma meta analysis aim identify prognostic value hepatitis b virus hbv hepatitis c virus hcv infections patients intrahepatic cholangiocarcinoma methods search performed relevant publications pubmed embase web science databases pooled effects calculated available information identify relationship hbv hcv infection prognosis clinicopathological features 2 2 tests used evaluate heterogeneity studies pooled hazard ratios hrs 95 confidence intervals cis calculated fixed effects model heterogeneity existed heterogeneity random effects model applied results total 14 studies involving 2842 cases enrolled meta analysis patients hbv infection presented better overall disease free survival pooled hrs significant 0 76 95 ci 0 70 0 83 0 78 95 ci 0 66 0 94 respectively additionally study revealed hcv infection correlated shortened overall survival comparison control group hr 2 64 95 ci 1 77 3 93 also found hbv infection occurred frequently male patients odds ratio 1 91 95 ci 1 06 3 44 correlated higher levels serum aspartate transaminase ast alpha fetoprotein afp 1 93 95 ci 1 11 3 35 3 86 95 ci 2 58 5 78 lower level serum carbohydrate antigen 19 9 ca19 9 0 47 95 ci 0 34 0 65 moreover hbv infection associated cirrhosis 6 44 95 ci 4 33 9 56 higher proportion capsule formation 6 04 95 ci 3 56 10 26 lower rate lymph node metastasis 0 39 95 ci 0 25 0 58 significant publication bias seen enrolled studies conclusion hbv infection may indicate favorable prognosis patients intrahepatic cholangiocarcinoma hcv infection suggests poor prognosis pubmed","probabilities":0.9799733,"Title":"Hepatitis B virus and hepatitis C virus play different prognostic roles in intrahepatic cholangiocarcinoma: A meta-analysis","Abstract":"AIM: To identify the prognostic value of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in patients with intrahepatic cholangiocarcinoma. METHODS: A search was performed for relevant publications in PubMed, EMBASE and Web of Science databases. The pooled effects were calculated from the available information to identify the relationship between HBV or HCV infection and the prognosis and clinicopathological features. The χ(2) and I (2) tests were used to evaluate heterogeneity between studies. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied. RESULTS: In total, 14 studies involving 2842 cases were enrolled in this meta-analysis. The patients with HBV infection presented better overall and disease-free survival, and the pooled HRs were significant at 0.76 (95%CI: 0.70-0.83) and 0.78 (95%CI: 0.66-0.94), respectively. Additionally, our study revealed that HCV infection was correlated with shortened overall survival in comparison with the control group (HR = 2.64, 95%CI: 1.77-3.93). We also found that HBV infection occurred more frequently in male patients [odds ratio (OR) = 1.91, 95%CI: 1.06-3.44] and was correlated with higher levels of serum aspartate transaminase (AST) and alpha-fetoprotein (AFP) (OR = 1.93, 95%CI: 1.11-3.35; OR = 3.86, 95%CI: 2.58-5.78) and a lower level of serum carbohydrate antigen 19-9 (CA19-9) (OR = 0.47, 95%CI: 0.34-0.65). Moreover, HBV infection was associated with cirrhosis (OR = 6.44, 95%CI: 4.33-9.56), a higher proportion of capsule formation (OR = 6.04, 95%CI: 3.56-10.26), and a lower rate of lymph node metastasis (OR = 0.39, 95%CI: 0.25-0.58). No significant publication bias was seen in any of the enrolled studies. CONCLUSION: HBV infection may indicate a favorable prognosis in patients with intrahepatic cholangiocarcinoma, while HCV infection suggests a poor prognosis.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis B virus and hepatitis C virus play different prognostic roles in intrahepatic cholangiocarcinoma: A meta-analysis AIM: To identify the prognostic value of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in patients with intrahepatic cholangiocarcinoma. METHODS: A search was performed for relevant publications in PubMed, EMBASE and Web of Science databases. The pooled effects were calculated from the available information to identify the relationship between HBV or HCV infection and the prognosis and clinicopathological features. The χ(2) and I (2) tests were used to evaluate heterogeneity between studies. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated by a fixed-effects model, if no heterogeneity existed. If there was heterogeneity, a random-effects model was applied. RESULTS: In total, 14 studies involving 2842 cases were enrolled in this meta-analysis. The patients with HBV infection presented better overall and disease-free survival, and the pooled HRs were significant at 0.76 (95%CI: 0.70-0.83) and 0.78 (95%CI: 0.66-0.94), respectively. Additionally, our study revealed that HCV infection was correlated with shortened overall survival in comparison with the control group (HR = 2.64, 95%CI: 1.77-3.93). We also found that HBV infection occurred more frequently in male patients [odds ratio (OR) = 1.91, 95%CI: 1.06-3.44] and was correlated with higher levels of serum aspartate transaminase (AST) and alpha-fetoprotein (AFP) (OR = 1.93, 95%CI: 1.11-3.35; OR = 3.86, 95%CI: 2.58-5.78) and a lower level of serum carbohydrate antigen 19-9 (CA19-9) (OR = 0.47, 95%CI: 0.34-0.65). Moreover, HBV infection was associated with cirrhosis (OR = 6.44, 95%CI: 4.33-9.56), a higher proportion of capsule formation (OR = 6.04, 95%CI: 3.56-10.26), and a lower rate of lymph node metastasis (OR = 0.39, 95%CI: 0.25-0.58). No significant publication bias was seen in any of the enrolled studies. CONCLUSION: HBV infection may indicate a favorable prognosis in patients with intrahepatic cholangiocarcinoma, while HCV infection suggests a poor prognosis. PubMed","prediction_labels":"HUMAN"},{"cleaned":"morbidity mortality major liver resection patients perihilar cholangiocarcinoma systematic review meta analysis background morbidity mortality hepatectomy perihilar cholangiocarcinoma known high however reported postoperative outcomes vary notable differences western asian series aimed determine morbidity mortality rates major hepatectomy patients perihilar cholangiocarcinoma assess differences outcome regarding geographic location hospital volume methods systematic review performed searching medline embase databases november 20 2017 risk bias assessed meta analysis metaregression performed using random effects model results total 51 studies included representing 4 634 patients pooled 30 day 90 day mortality 5 95 ci 3 6 9 95 ci 6 12 respectively pooled overall morbidity severe morbidity 57 95 ci 50 64 40 95 ci 34 47 respectively western studies compared asian studies significantly higher 30 day mortality 90 day mortality overall morbidity 8 versus 2 p 001 12 versus 3 p 001 63 versus 54 p 048 respectively effect mortality remained significant correcting hospital volume univariate metaregression analysis showed influence hospital volume mortality morbidity corrected geographic location higher hospital volume associated higher severe morbidity p 039 conclusion morbidity mortality rates major hepatectomy perihilar cholangiocarcinoma high western series showed higher mortality compared asian series even corrected hospital volume standardized reporting outcomes necessary underlying causes differences outcomes asian western centers differences treatment strategies analyzed pubmed","probabilities":0.9799733,"Title":"Morbidity and mortality after major liver resection in patients with perihilar cholangiocarcinoma: A systematic review and meta-analysis","Abstract":"BACKGROUND: Morbidity and mortality after hepatectomy for perihilar cholangiocarcinoma are known to be high. However, reported postoperative outcomes vary, with notable differences between Western and Asian series. We aimed to determine morbidity and mortality rates after major hepatectomy in patients with perihilar cholangiocarcinoma and assess differences in outcome regarding geographic location and hospital volume. METHODS: A systematic review was performed by searching the MEDLINE and EMBASE databases through November 20, 2017. Risk of bias was assessed and meta-analysis and metaregression were performed using a random effects model. RESULTS: A total of 51 studies were included, representing 4,634 patients. Pooled 30-day and 90-day mortality were 5% (95% CI 3%-6%) and 9% (95% CI 6%-12%), respectively. Pooled overall morbidity and severe morbidity were 57% (95% CI 50%-64%) and 40% (95% CI 34%-47%), respectively. Western studies compared with Asian studies had a significantly higher 30-day mortality, 90-day mortality, and overall morbidity: 8% versus 2% (P < .001), 12% versus 3% (P < .001), and 63% versus 54% (P = .048), respectively. This effect on mortality remained significant after correcting for hospital volume. Univariate metaregression analysis showed no influence of hospital volume on mortality or morbidity, but when corrected for geographic location, higher hospital volume was associated with higher severe morbidity (P = .039). CONCLUSION: Morbidity and mortality rates after major hepatectomy for perihilar cholangiocarcinoma are high. The Western series showed a higher mortality compared with the Asian series, even when corrected for hospital volume. Standardized reporting of outcomes is necessary. Underlying causes for differences in outcomes between Asian and Western centers, such as differences in treatment strategies, should be further analyzed.","Source":"PubMed","category":"HUMAN","training_data":"Morbidity and mortality after major liver resection in patients with perihilar cholangiocarcinoma: A systematic review and meta-analysis BACKGROUND: Morbidity and mortality after hepatectomy for perihilar cholangiocarcinoma are known to be high. However, reported postoperative outcomes vary, with notable differences between Western and Asian series. We aimed to determine morbidity and mortality rates after major hepatectomy in patients with perihilar cholangiocarcinoma and assess differences in outcome regarding geographic location and hospital volume. METHODS: A systematic review was performed by searching the MEDLINE and EMBASE databases through November 20, 2017. Risk of bias was assessed and meta-analysis and metaregression were performed using a random effects model. RESULTS: A total of 51 studies were included, representing 4,634 patients. Pooled 30-day and 90-day mortality were 5% (95% CI 3%-6%) and 9% (95% CI 6%-12%), respectively. Pooled overall morbidity and severe morbidity were 57% (95% CI 50%-64%) and 40% (95% CI 34%-47%), respectively. Western studies compared with Asian studies had a significantly higher 30-day mortality, 90-day mortality, and overall morbidity: 8% versus 2% (P < .001), 12% versus 3% (P < .001), and 63% versus 54% (P = .048), respectively. This effect on mortality remained significant after correcting for hospital volume. Univariate metaregression analysis showed no influence of hospital volume on mortality or morbidity, but when corrected for geographic location, higher hospital volume was associated with higher severe morbidity (P = .039). CONCLUSION: Morbidity and mortality rates after major hepatectomy for perihilar cholangiocarcinoma are high. The Western series showed a higher mortality compared with the Asian series, even when corrected for hospital volume. Standardized reporting of outcomes is necessary. Underlying causes for differences in outcomes between Asian and Western centers, such as differences in treatment strategies, should be further analyzed. PubMed","prediction_labels":"HUMAN"},{"cleaned":"micrornas benign biliary tract diseases cholangiocytes epithelial cells lining biliary tree represent small portion total liver cell population 3 5 responsible secretion 40 total daily bile volume addition cholangiocytes target diverse group liver diseases affecting biliary tract cholangiopathies conditions pathological mechanisms unclear micrornas mirnas small noncoding rnas posttranscriptionally regulate gene expression thus surprising altered mirna profiles underlie dysregulation several proteins involved pathobiology cholangiopathies well showing promise diagnostic prognostic tools authors review recent work relevant role mirnas etiopathogenesis several cholangiopathies e fibroinflammatory cholangiopathies polycystic liver diseases discuss value prognostic diagnostic tools provide suggestions research pubmed","probabilities":0.962963,"Title":"MicroRNAs and benign biliary tract diseases","Abstract":"Cholangiocytes, the epithelial cells lining the biliary tree, represent only a small portion of the total liver cell population (3-5%), but they are responsible for the secretion of up to 40% of total daily bile volume. In addition, cholangiocytes are the target of a diverse group of liver diseases affecting the biliary tract, the cholangiopathies; for most of these conditions, the pathological mechanisms are unclear. MicroRNAs (miRNAs) are small, noncoding RNAs that posttranscriptionally regulate gene expression. Thus, it is not surprising that altered miRNA profiles underlie the dysregulation of several proteins involved in the pathobiology of the cholangiopathies, as well as showing promise as diagnostic and prognostic tools. Here the authors review recent work relevant to the role of miRNAs in the etiopathogenesis of several of the cholangiopathies (i.e., fibroinflammatory cholangiopathies and polycystic liver diseases), discuss their value as prognostic and diagnostic tools, and provide suggestions for further research.","Source":"PubMed","category":"HUMAN","training_data":"MicroRNAs and benign biliary tract diseases Cholangiocytes, the epithelial cells lining the biliary tree, represent only a small portion of the total liver cell population (3-5%), but they are responsible for the secretion of up to 40% of total daily bile volume. In addition, cholangiocytes are the target of a diverse group of liver diseases affecting the biliary tract, the cholangiopathies; for most of these conditions, the pathological mechanisms are unclear. MicroRNAs (miRNAs) are small, noncoding RNAs that posttranscriptionally regulate gene expression. Thus, it is not surprising that altered miRNA profiles underlie the dysregulation of several proteins involved in the pathobiology of the cholangiopathies, as well as showing promise as diagnostic and prognostic tools. Here the authors review recent work relevant to the role of miRNAs in the etiopathogenesis of several of the cholangiopathies (i.e., fibroinflammatory cholangiopathies and polycystic liver diseases), discuss their value as prognostic and diagnostic tools, and provide suggestions for further research. PubMed","prediction_labels":"HUMAN"},{"cleaned":"albumin bilirubin grade novel predictor survival advanced extrahepatic cholangiocarcinoma aim child pugh cp grade used assess liver function postoperative outcomes biliary tract neoplasms aim study preliminarily explore prognostic significance alternative model liver function called albumin bilirubin albi grade patients extrahepatic cholangiocarcinoma ehc methods total 109 advanced ehc patients received percutaneous transhepatic biliary stenting combined iodine 125 seed implantation january 2012 april 2017 department enrolled preoperative clinical data collected calculate cp albi grades performance albi score predicting postoperative death compared cp score using receiver operating characteristic roc curve kaplan meier analysis cox regression model performed overall survival os analysis results median survival time cohort 12 months 1 year 2 year survival rates 56 9 12 8 respectively area roc curve albi score predicting death significantly greater cp score 0 751 95 ci 0 641 0 861 p 0 001 vs 0 688 95 ci 0 567 0 809 p 0 001 univariate analysis revealed factors related overall survival ehc carbohydrate antigen 19 9 total bilirubin albumin albi grade cp score multivariate analysis albi grade hr 1 65 95 ci 1 04 2 61 p 0 032 cp score identified independent prognostic model conclusion demonstrated albi grade used predictor survival unresectable ehc patients stn","probabilities":0.9799733,"Title":"Albumin-Bilirubin Grade As A Novel Predictor Of Survival In Advanced Extrahepatic Cholangiocarcinoma","Abstract":"Aim: Child-Pugh (CP) grade has been used to assess liver function and postoperative outcomes in biliary tract neoplasms. The aim of this study was to preliminarily explore the prognostic significance of an alternative model of liver function, called albumin-bilirubin (ALBI) grade, in patients with extrahepatic cholangiocarcinoma (EHC). \r\n\r\n Methods: A total of 109 advanced EHC patients, who received percutaneous transhepatic biliary stenting combined with iodine-125 seed implantation from January 2012 to April 2017 in our department, were enrolled. Preoperative clinical data were collected to calculate the CP and ALBI grades. The performance of ALBI score in predicting postoperative death was compared with that of CP score by using the receiver operating characteristic (ROC) curve. Kaplan-Meier analysis and Cox regression model were performed for overall survival (OS) analysis. \r\n\r\n Results: The median survival time of our cohort was 12 months, and the 1-year and 2-year survival rates were 56.9% and 12.8%, respectively. The area under the ROC curve of ALBI score for predicting death was significantly greater than the CP score (0.751, 95% CI: 0.641-0.861, P < 0.001 vs. 0.688, 95% CI: 0.567-0.809, P < 0.001). The univariate analysis revealed that the factors related to overall survival of EHC were carbohydrate antigen 19-9, total bilirubin, albumin, ALBI grade, and CP score. In multivariate analysis, ALBI grade (HR = 1.65, 95% CI: 1.04-2.61, P = 0.032), but not CP score, was identified as an independent prognostic model. \r\n\r\n Conclusion: We demonstrated that the ALBI grade could be used as a predictor of survival in unresectable EHC patients.","Source":"STN","category":"HUMAN","training_data":"Albumin-Bilirubin Grade As A Novel Predictor Of Survival In Advanced Extrahepatic Cholangiocarcinoma Aim: Child-Pugh (CP) grade has been used to assess liver function and postoperative outcomes in biliary tract neoplasms. The aim of this study was to preliminarily explore the prognostic significance of an alternative model of liver function, called albumin-bilirubin (ALBI) grade, in patients with extrahepatic cholangiocarcinoma (EHC). \r\n\r\n Methods: A total of 109 advanced EHC patients, who received percutaneous transhepatic biliary stenting combined with iodine-125 seed implantation from January 2012 to April 2017 in our department, were enrolled. Preoperative clinical data were collected to calculate the CP and ALBI grades. The performance of ALBI score in predicting postoperative death was compared with that of CP score by using the receiver operating characteristic (ROC) curve. Kaplan-Meier analysis and Cox regression model were performed for overall survival (OS) analysis. \r\n\r\n Results: The median survival time of our cohort was 12 months, and the 1-year and 2-year survival rates were 56.9% and 12.8%, respectively. The area under the ROC curve of ALBI score for predicting death was significantly greater than the CP score (0.751, 95% CI: 0.641-0.861, P < 0.001 vs. 0.688, 95% CI: 0.567-0.809, P < 0.001). The univariate analysis revealed that the factors related to overall survival of EHC were carbohydrate antigen 19-9, total bilirubin, albumin, ALBI grade, and CP score. In multivariate analysis, ALBI grade (HR = 1.65, 95% CI: 1.04-2.61, P = 0.032), but not CP score, was identified as an independent prognostic model. \r\n\r\n Conclusion: We demonstrated that the ALBI grade could be used as a predictor of survival in unresectable EHC patients. STN","prediction_labels":"HUMAN"},{"cleaned":"preoperative predictors incidental gallbladder cancer routine cholecystectomy purpose 1 cases incidental gallbladder cancers igbc found routine cholecystectomy aim study compare clinical features igbc benign gb disease evaluate factors affecting recurrence survival methods january 1998 march 2014 4 629 patients received cholecystectomy 73 igbc patients 1 6 identified compared clinical features 4 556 benign gb disease patients 73 igbc patients evaluated operative outcomes prognostic factors 56 eligible patients results igbc patients older concomitant diseases hypertension anemia common benign ones age 65 years risk factor igbc adverse prognostic factors affecting patients survival age 65 advanced histology lymph node metastasis lymphovascular invasion multivariate analysis age 65 years lymph node involvement lymphovascular invasion identified unfavorable factors affecting survival subgroup analysis extended cholecystectomy bile duct resection ec bdr n 22 conclusion prior routine cholecystectomy incidental gb cancer suspected especially elderly patients advanced age lymph node metastasis lymphovascular invasion important prognostic factors ec bdr cohorts stn","probabilities":0.9799733,"Title":"What Are Preoperative Predictors For Incidental Gallbladder Cancer After Routine Cholecystectomy?","Abstract":"Purpose: In about 1% of cases, incidental gallbladder cancers (iGBC) are found after routine cholecystectomy. The aim of this study is to compare clinical features of iGBC with benign GB disease and to evaluate factors affecting recurrence and survival. \r\n\r\n Methods: Between January 1998 and March 2014, 4,629 patients received cholecystectomy and 73 iGBC patients (1.6%) were identified. We compared clinical features of 4,556 benign GB disease patients with 73 iGBC patients, and evaluated operative outcomes and prognostic factors in 56 eligible patients. \r\n\r\n Results: The iGBC patients were older and concomitant diseases such as hypertension and anemia were more common than benign ones. And an age of more than 65 years was the only risk factor of iGBC. Adverse prognostic factors affecting patients' survival were age over 65, advanced histology, lymph node metastasis, and lymphovascular invasion on multivariate analysis. Age over 65 years, lymph node involvement, and lymphovascular invasion were identified as unfavorable factors affecting survival in subgroup analysis of extended cholecystectomy with bile duct resection (EC with BDR, n = 22). \r\n\r\n Conclusion: Prior to routine cholecystectomy, incidental GB cancer should be suspected especially in elderly patients. And advanced age, lymph node metastasis, and lymphovascular invasion are important prognostic factors in EC with BDR cohorts.","Source":"STN","category":"HUMAN","training_data":"What Are Preoperative Predictors For Incidental Gallbladder Cancer After Routine Cholecystectomy? Purpose: In about 1% of cases, incidental gallbladder cancers (iGBC) are found after routine cholecystectomy. The aim of this study is to compare clinical features of iGBC with benign GB disease and to evaluate factors affecting recurrence and survival. \r\n\r\n Methods: Between January 1998 and March 2014, 4,629 patients received cholecystectomy and 73 iGBC patients (1.6%) were identified. We compared clinical features of 4,556 benign GB disease patients with 73 iGBC patients, and evaluated operative outcomes and prognostic factors in 56 eligible patients. \r\n\r\n Results: The iGBC patients were older and concomitant diseases such as hypertension and anemia were more common than benign ones. And an age of more than 65 years was the only risk factor of iGBC. Adverse prognostic factors affecting patients' survival were age over 65, advanced histology, lymph node metastasis, and lymphovascular invasion on multivariate analysis. Age over 65 years, lymph node involvement, and lymphovascular invasion were identified as unfavorable factors affecting survival in subgroup analysis of extended cholecystectomy with bile duct resection (EC with BDR, n = 22). \r\n\r\n Conclusion: Prior to routine cholecystectomy, incidental GB cancer should be suspected especially in elderly patients. And advanced age, lymph node metastasis, and lymphovascular invasion are important prognostic factors in EC with BDR cohorts. STN","prediction_labels":"HUMAN"},{"cleaned":"effect temperature killing opisthorchis viverrini eggs vitro contaminated liver fluke egg environment led high prevalence human opisthorchiasis associated cholangiocarcinoma southeast asia find effective lessening methods opisthorchis viverrini eggs contaminated environment investigated temperature conditions killing trematode eggs vitro numerous o viverrini eggs obtained proximal part uteri adult worms experimental hamsters mature eggs miracidium allocated experimental groups 2 control positive negative 4 treatment 50 60 70 80 c 0 85 saline treated experimental plan eggs experimental groups observed confocal microscope stain propidium iodide pi evaluate effect temperatures eggs 70 80 c groups killed 10 min heated majority eggs 60 c 10 15 30 min heated 70 80 c 5 min heated groups inactivated however 50 c group half eggs killed time lapse 10 15 30 min order prevent o viverrini infection cholangiocarcinoma direct treatment sewage heating 70 80 c least 10 min essential therefore treatment o viverrini eggs high temperature potential method controlling egg contamination sewage stn","probabilities":1.0,"Title":"Effect Of Temperature On The Killing Of Opisthorchis Viverrini Eggs In Vitro","Abstract":"Contaminated liver fluke egg in the environment has led to the high prevalence of human opisthorchiasis associated with cholangiocarcinoma in Southeast Asia. To find the effective lessening methods of Opisthorchis viverrini eggs in the contaminated environment, we investigated the temperature conditions for killing of these trematode eggs in vitro. Numerous O. viverrini eggs were obtained in the proximal part of uteri of adult worms from experimental hamsters. Mature eggs with miracidium were allocated by experimental groups (2 control: positive and negative and 4 treatment: 50, 60, 70, and 80°C) with 0.85% saline, and treated by the experimental plan. Eggs in each experimental groups were observed under the confocal microscope after stain with Propidium Iodide (PI) to evaluate the effect of temperatures. Eggs in 70 and 80°C groups were all killed after over 10 min heated. Majority of eggs in 60°C (10, 15, and 30 min heated), 70 and 80°C (5 min heated) groups were inactivated. However in 50°C group, below half of eggs were to be killed in all time lapse (10, 15 and 30 min). In order to prevent O. viverrini infection and cholangiocarcinoma, direct treatment of sewage by heating at 70 or 80°C at least 10 min is essential. Therefore, treatment of O. viverrini eggs at a high temperature is a potential method for controlling egg contamination in sewage.","Source":"STN","category":"ANIMAL","training_data":"Effect Of Temperature On The Killing Of Opisthorchis Viverrini Eggs In Vitro Contaminated liver fluke egg in the environment has led to the high prevalence of human opisthorchiasis associated with cholangiocarcinoma in Southeast Asia. To find the effective lessening methods of Opisthorchis viverrini eggs in the contaminated environment, we investigated the temperature conditions for killing of these trematode eggs in vitro. Numerous O. viverrini eggs were obtained in the proximal part of uteri of adult worms from experimental hamsters. Mature eggs with miracidium were allocated by experimental groups (2 control: positive and negative and 4 treatment: 50, 60, 70, and 80°C) with 0.85% saline, and treated by the experimental plan. Eggs in each experimental groups were observed under the confocal microscope after stain with Propidium Iodide (PI) to evaluate the effect of temperatures. Eggs in 70 and 80°C groups were all killed after over 10 min heated. Majority of eggs in 60°C (10, 15, and 30 min heated), 70 and 80°C (5 min heated) groups were inactivated. However in 50°C group, below half of eggs were to be killed in all time lapse (10, 15 and 30 min). In order to prevent O. viverrini infection and cholangiocarcinoma, direct treatment of sewage by heating at 70 or 80°C at least 10 min is essential. Therefore, treatment of O. viverrini eggs at a high temperature is a potential method for controlling egg contamination in sewage. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic factors patients advanced extrahepatic cholangiocarcinoma single center experience extrahepatic cholangiocarcinoma ecc aggressive malignancy causing lot fatalities comorbidities endoscopic biliary stenting ebs mostly needed ecc study aimed investigate prognostic factors overall survival os factors predicting patients eligible chemotherapy ebs ecc retrospectively screened 153 advanced ecc patients underwent ebs jaundice make patients eligible chemotherapy patient clinical laboratory parameters recorded os estimated kaplan meier method parameters assessed binary logistic regression analysis predict patients eligible chemotherapy median os patients 12 0 months 10 1 13 8 median os patients treated chemotherapy 13 0 months 12 0 14 0 4 0 months 2 3 5 7 patients unable chemotherapy ebs albumin aspartate aminotransferase alt carbohydrate antigen 19 9 ca 19 9 values independent prognostic factors os higher albumin lower prothrombin time pt levels independent parameters predict patients eligible chemotherapy ebs suitable chemotherapy main determinant prolonged survival albumin pt levels independent predictors chemotherapy eligibility ebs albumin alt ca 19 9 values independent prognostic factors os ecc pubmed","probabilities":0.9799733,"Title":"Prognostic factors in patients with advanced extrahepatic cholangiocarcinoma: A single center experience","Abstract":"Extrahepatic cholangiocarcinoma (ECC) is an aggressive malignancy causing a lot of fatalities and comorbidities. Endoscopic biliary stenting (EBS) is mostly needed for ECC. In this study, we aimed to investigate the prognostic factors for the overall survival (OS) and the factors predicting the patients eligible for chemotherapy after EBS in ECC.We retrospectively screened 153 advanced ECC patients who underwent EBS for jaundice to make the patients eligible for chemotherapy. Patient's clinical and laboratory parameters were recorded. OS was estimated by the Kaplan-Meier method. All parameters were assessed by binary logistic regression analysis to predict which patients are eligible for chemotherapy.The median OS of all patients was 12.0 months (10.1-13.8). The median OS of the patients treated with chemotherapy was 13.0 months (12.0-14.0), while it was 4.0 months (2.3-5.7) for patients unable for chemotherapy after EBS. Albumin, aspartate aminotransferase (ALT) and carbohydrate antigen 19-9 (CA 19-9) values were independent prognostic factors for OS. Higher albumin and lower prothrombin time (PT) levels were independent parameters to predict the patients eligible for chemotherapy after EBS.Being suitable for chemotherapy was the main determinant for prolonged survival and albumin and PT levels were independent predictors for chemotherapy eligibility after EBS. Albumin, ALT, and CA 19-9 values were independent prognostic factors for OS in ECC.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic factors in patients with advanced extrahepatic cholangiocarcinoma: A single center experience Extrahepatic cholangiocarcinoma (ECC) is an aggressive malignancy causing a lot of fatalities and comorbidities. Endoscopic biliary stenting (EBS) is mostly needed for ECC. In this study, we aimed to investigate the prognostic factors for the overall survival (OS) and the factors predicting the patients eligible for chemotherapy after EBS in ECC.We retrospectively screened 153 advanced ECC patients who underwent EBS for jaundice to make the patients eligible for chemotherapy. Patient's clinical and laboratory parameters were recorded. OS was estimated by the Kaplan-Meier method. All parameters were assessed by binary logistic regression analysis to predict which patients are eligible for chemotherapy.The median OS of all patients was 12.0 months (10.1-13.8). The median OS of the patients treated with chemotherapy was 13.0 months (12.0-14.0), while it was 4.0 months (2.3-5.7) for patients unable for chemotherapy after EBS. Albumin, aspartate aminotransferase (ALT) and carbohydrate antigen 19-9 (CA 19-9) values were independent prognostic factors for OS. Higher albumin and lower prothrombin time (PT) levels were independent parameters to predict the patients eligible for chemotherapy after EBS.Being suitable for chemotherapy was the main determinant for prolonged survival and albumin and PT levels were independent predictors for chemotherapy eligibility after EBS. Albumin, ALT, and CA 19-9 values were independent prognostic factors for OS in ECC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"role adjuvant chemoradiotherapy resected extrahepatic biliary tract cancer purpose evaluate effect adjuvant chemoradiotherapy crt locoregional control lrc disease free survival dfs overall survival os patients extrahepatic biliary tract cancer treated curative resection methods materials study involved 168 patients extrahepatic biliary tract cancer undergoing curative resection august 2001 april 2009 168 patients 115 received adjuvant crt crt group 53 crt group gender age tumor size histologic differentiation pre postoperative carbohydrate antigen 19 9 level resection margin vascular invasion perineural invasion stage n stage overall stage use adjuvant crt analyzed identify prognostic factors associated lrc dfs os results patients 5 year lrc dfs os rate 54 8 30 6 33 9 respectively univariate analysis 5 year lrc dfs os rates crt group significantly better crt group 58 5 vs 44 4 p 007 32 1 vs 26 1 p 041 36 5 vs 28 2 p 049 respectively multivariate analysis revealed adjuvant crt significant independent prognostic factor lrc dfs os p 05 conclusion results suggested adjuvant crt helps achieve lrc consequently improves dfs os patients extrahepatic biliary tract cancer stn","probabilities":0.9799733,"Title":"The Role Of Adjuvant Chemoradiotherapy In Resected Extrahepatic Biliary Tract Cancer","Abstract":"Purpose: To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. \r\n\r\n Methods and materials: The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. \r\n\r\n Results: For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p=.007; 32.1% vs. 26.1%, p=.041; 36.5% vs. 28.2%, p=.049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p<.05). \r\n\r\n Conclusion: Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer.","Source":"STN","category":"HUMAN","training_data":"The Role Of Adjuvant Chemoradiotherapy In Resected Extrahepatic Biliary Tract Cancer Purpose: To evaluate the effect of adjuvant chemoradiotherapy (CRT) on locoregional control (LRC), disease-free survival (DFS), and overall survival (OS) for patients with extrahepatic biliary tract cancer treated with curative resection. \r\n\r\n Methods and materials: The study involved 168 patients with extrahepatic biliary tract cancer undergoing curative resection between August 2001 and April 2009. Of the 168 patients, 115 received adjuvant CRT (CRT group) and 53 did not (no-CRT group). Gender, age, tumor size, histologic differentiation, pre- and postoperative carbohydrate antigen 19-9 level, resection margin, vascular invasion, perineural invasion, T stage, N stage, overall stage, and the use of adjuvant CRT were analyzed to identify the prognostic factors associated with LRC, DFS, and OS. \r\n\r\n Results: For all patients, the 5-year LRC, DFS, and OS rate was 54.8%, 30.6%, and 33.9%, respectively. On univariate analysis, the 5-year LRC, DFS, and OS rates in the CRT group were significantly better than those in the no-CRT group (58.5% vs. 44.4%, p=.007; 32.1% vs. 26.1%, p=.041; 36.5% vs. 28.2%, p=.049, respectively). Multivariate analysis revealed that adjuvant CRT was a significant independent prognostic factor for LRC, DFS, and OS (p<.05). \r\n\r\n Conclusion: Our results have suggested that adjuvant CRT helps achieve LRC and, consequently, improves DFS and OS in patients with extrahepatic biliary tract cancer. STN","prediction_labels":"HUMAN"},{"cleaned":"high expression cxcr4 cxcr7 predicts poor survival gallbladder cancer chemokine receptors play prominent role cancer progression metastasis study investigated whether expression cxc chemokine receptor types 4 7 cxcr4 cxcr7 respectively determined immunohistochemically associated clinicopathological characteristics postoperative survival gallbladder cancer specimens 72 patients cxcr4 detected cytoplasm nucleus gallbladder cancer cells cxcr7 detected cytoplasm expression either cxcr7 cxcr4 cytoplasm associated tumour stage expression nuclear cxcr4 associated lymph node metastases lymphatic invasion cytoplasmic expression cxcr4 cxcr7 independent risk factors worse postoperative survival research required clarify mechanisms involved associations determine potential prognostic therapeutic implications pubmed","probabilities":0.9799733,"Title":"High expression of CXCR4 and CXCR7 predicts poor survival in gallbladder cancer","Abstract":"Chemokine receptors play a prominent role in cancer progression and metastasis. This study investigated whether the expression of CXC chemokine receptor types 4 and 7 (CXCR4 and CXCR7, respectively), determined immunohistochemically, was associated with clinicopathological characteristics and postoperative survival in gallbladder cancer specimens from 72 patients. CXCR4 was detected in the cytoplasm and/or nucleus of gallbladder cancer cells, but CXCR7 was detected only in the cytoplasm. Expression of either CXCR7 or CXCR4 in the cytoplasm was associated with tumour stage. Expression of nuclear CXCR4 was associated with lymph node metastases and lymphatic invasion. Cytoplasmic expression of CXCR4 and CXCR7 were each independent risk factors for worse postoperative survival. Further research is required to clarify the mechanisms involved in these associations and to determine their potential prognostic and therapeutic implications.","Source":"PubMed","category":"HUMAN","training_data":"High expression of CXCR4 and CXCR7 predicts poor survival in gallbladder cancer Chemokine receptors play a prominent role in cancer progression and metastasis. This study investigated whether the expression of CXC chemokine receptor types 4 and 7 (CXCR4 and CXCR7, respectively), determined immunohistochemically, was associated with clinicopathological characteristics and postoperative survival in gallbladder cancer specimens from 72 patients. CXCR4 was detected in the cytoplasm and/or nucleus of gallbladder cancer cells, but CXCR7 was detected only in the cytoplasm. Expression of either CXCR7 or CXCR4 in the cytoplasm was associated with tumour stage. Expression of nuclear CXCR4 was associated with lymph node metastases and lymphatic invasion. Cytoplasmic expression of CXCR4 and CXCR7 were each independent risk factors for worse postoperative survival. Further research is required to clarify the mechanisms involved in these associations and to determine their potential prognostic and therapeutic implications. PubMed","prediction_labels":"HUMAN"},{"cleaned":"erk mapk pathway overexpressed activated gallbladder cancer gallbladder cancer gbc highly fatal disease poor prognosis therapeutic alternatives molecular profiling revealed deregulation erk mapk signaling pathway plays crucial role many disease malignancies including gbc aim study measure expression erk1 2 p erk1 2 population high gbc related mortality chilean population characterize protein expression erk mapk pathway seven gbc cell lines immunohistochemistry ihc erk1 2 p erk1 2 performed 123 gbc tissues 37 chronic cholecystitis cc tissues addition protein expression analysis western blot erk1 2 p erk1 2 egfr erbb2 erbb3 performed seven gbc cell lines gb d1 g415 noz ocug 1 tgbc 1 tgbc 2 tgbc 24 higher erk1 2 p erk1 2 expression found gbc tissues compared chronic cholecystitis cc tissues p 0 001 however neither significant differences overall survival significant associations clinicopathological features found comparing low high expression erk1 2 p erk1 2 western blot analysis seven gbc cell lines showed general gb d1 g415 noz cells evidenced strong expression erk1 2 p erk1 2 egfr erbb2 erbb3 therefore erk1 2 p erk1 2 seem important development gbc gb d1 g415 noz cell lines may used experimental models vitro vivo studies help decipher role mapk erk pathway gallbladder carcinogenesis stn","probabilities":0.9467213,"Title":"The Erk/Mapk Pathway Is Overexpressed And Activated In Gallbladder Cancer","Abstract":"Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular profiling has revealed that the deregulation in the ERK/MAPK signaling pathway plays a crucial role in many disease and malignancies, including GBC. The aim of this study was to measure the expression of ERK1/2 and p-ERK1/2 in a population with high GBC-related mortality, such as the Chilean population, and characterize the protein expression of this ERK/MAPK pathway in seven GBC cell lines. Immunohistochemistry (IHC) for ERK1/2 and p-ERK1/2 was performed in 123 GBC tissues and 37 chronic cholecystitis (CC) tissues. In addition, protein expression analysis by western blot for ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3 were performed in seven GBC cell lines (GB-d1, G415, NOZ, OCUG-1, TGBC-1, TGBC-2 and TGBC-24). A higher ERK1/2 and p-ERK1/2 expression was found in GBC tissues compared to chronic cholecystitis (CC) tissues (P<0.001). However, neither significant differences in overall survival nor significant associations with any of the clinicopathological features were found by comparing low and high expression of both ERK1/2 and p-ERK1/2. Western blot analysis of seven GBC cell lines showed that, in general, GB-d1, G415 and NOZ cells evidenced a strong expression of ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3. Therefore, ERK1/2 and p-ERK1/2 seem to be important in the development of GBC and GB-d1, G415 and NOZ cell lines may be used as experimental models for further in vitro and in vivo studies that help to decipher the role of MAPK/ERK pathway in gallbladder carcinogenesis.","Source":"STN","category":"ANIMAL","training_data":"The Erk/Mapk Pathway Is Overexpressed And Activated In Gallbladder Cancer Gallbladder cancer (GBC) is a highly fatal disease with poor prognosis and few therapeutic alternatives. Molecular profiling has revealed that the deregulation in the ERK/MAPK signaling pathway plays a crucial role in many disease and malignancies, including GBC. The aim of this study was to measure the expression of ERK1/2 and p-ERK1/2 in a population with high GBC-related mortality, such as the Chilean population, and characterize the protein expression of this ERK/MAPK pathway in seven GBC cell lines. Immunohistochemistry (IHC) for ERK1/2 and p-ERK1/2 was performed in 123 GBC tissues and 37 chronic cholecystitis (CC) tissues. In addition, protein expression analysis by western blot for ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3 were performed in seven GBC cell lines (GB-d1, G415, NOZ, OCUG-1, TGBC-1, TGBC-2 and TGBC-24). A higher ERK1/2 and p-ERK1/2 expression was found in GBC tissues compared to chronic cholecystitis (CC) tissues (P<0.001). However, neither significant differences in overall survival nor significant associations with any of the clinicopathological features were found by comparing low and high expression of both ERK1/2 and p-ERK1/2. Western blot analysis of seven GBC cell lines showed that, in general, GB-d1, G415 and NOZ cells evidenced a strong expression of ERK1/2, p-ERK1/2, EGFR, ERBB2 and ERBB3. Therefore, ERK1/2 and p-ERK1/2 seem to be important in the development of GBC and GB-d1, G415 and NOZ cell lines may be used as experimental models for further in vitro and in vivo studies that help to decipher the role of MAPK/ERK pathway in gallbladder carcinogenesis. STN","prediction_labels":"ANIMAL"},{"cleaned":"gallbladder neoplasm single institution experience according standard current management aim aim paper determine aggressive surgical approach increase r0 resections resulted improved survival patients gallbladder cancer gallbladder cancer silent disease despite efforts prognosis remains dismal consensus among surgeons regarding indications extent resection lymph node dissection port site resection bile duct management reached methods retrospective review patients gallbladder cancer admitted 12 years period conducted sixteen patients identified cases divided 2 cohorts surgical treated group stg n 10 non surgical treated group nstg n 6 results nstg disease metastatic stage iv liver 33 3 peritoneum 50 liver peritoneum 16 7 stg 13 procedures performed 6 liver resection 2 en bloc resection 2 bisegmentectomy 2 wedge resection 7 cholecystectomies 6 r1 7 r0 resections liver resections r0 0 mortality 30 7 morbidity complications managed conservatively length stay 10 days stg 5 days nstg median overall survival 10 months std error 2 381 ci 5 333 14 667 stg 16 months std error 6 275 ci 3 701 28 299 nstg 7 months std error 2 381 ci 5 337 14 667 conclusion whenever possible radical resection free margin r0 must achieved chance treat efficiently pubmed","probabilities":0.9799733,"Title":"Gallbladder neoplasm: a single institution experience according to the standard current management","Abstract":"AIM: The aim of this paper was to determine if an aggressive surgical approach, with an increase in R0 resections, has resulted in improved survival for patients with gallbladder cancer. Gallbladder cancer is a silent disease, despite the efforts, the prognosis remains dismal. Consensus among surgeons regarding the indications for the extent of resection, lymph node dissection, port site resection, bile duct management has not been reached. METHODS: A retrospective review of all patients with gallbladder cancer admitted during 12 years period was conducted. Sixteen patients were identified. Cases were divided into 2 cohorts surgical treated group (STG, N.=10) and non surgical treated group (NSTG, N.=6). RESULTS: In NSTG the disease was metastatic (stage IV): liver (33.3%), peritoneum (50%), liver and peritoneum (16.7%). In STG 13 procedures were performed, 6 liver resection (2 en bloc resection, 2 bisegmentectomy, 2 wedge resection) 7 cholecystectomies. 6 R1, 7 R0 resections. All the liver resections were R0. 0% mortality, 30.7% of morbidity, all the complications were managed conservatively. Length of stay was 10 days for the STG, and 5 days for the NSTG. The median overall survival was 10 months (Std Error 2.381 CI 5.333-14.667), while in the STG 16 months (Std Error 6.275 CI 3.701-28.299) and in the NSTG was 7 months (Std Error 2.381 CI 5.337-14.667) CONCLUSION: Whenever is possible radical resection with free margin (R0) must be achieved, being the only chance to treat efficiently.","Source":"PubMed","category":"HUMAN","training_data":"Gallbladder neoplasm: a single institution experience according to the standard current management AIM: The aim of this paper was to determine if an aggressive surgical approach, with an increase in R0 resections, has resulted in improved survival for patients with gallbladder cancer. Gallbladder cancer is a silent disease, despite the efforts, the prognosis remains dismal. Consensus among surgeons regarding the indications for the extent of resection, lymph node dissection, port site resection, bile duct management has not been reached. METHODS: A retrospective review of all patients with gallbladder cancer admitted during 12 years period was conducted. Sixteen patients were identified. Cases were divided into 2 cohorts surgical treated group (STG, N.=10) and non surgical treated group (NSTG, N.=6). RESULTS: In NSTG the disease was metastatic (stage IV): liver (33.3%), peritoneum (50%), liver and peritoneum (16.7%). In STG 13 procedures were performed, 6 liver resection (2 en bloc resection, 2 bisegmentectomy, 2 wedge resection) 7 cholecystectomies. 6 R1, 7 R0 resections. All the liver resections were R0. 0% mortality, 30.7% of morbidity, all the complications were managed conservatively. Length of stay was 10 days for the STG, and 5 days for the NSTG. The median overall survival was 10 months (Std Error 2.381 CI 5.333-14.667), while in the STG 16 months (Std Error 6.275 CI 3.701-28.299) and in the NSTG was 7 months (Std Error 2.381 CI 5.337-14.667) CONCLUSION: Whenever is possible radical resection with free margin (R0) must be achieved, being the only chance to treat efficiently. PubMed","prediction_labels":"HUMAN"},{"cleaned":"radioembolization 90 y resin microspheres intrahepatic cholangiocellular carcinoma prognostic factors aim investigate prognostic factors predict overall survival radioembolization patients cholangiocellular carcinoma methods study comprised 16 patients received radioembolization y 90 resin microspheres cholangiocarcinoma statistical relationships overall survival radioembolization age number dimension fluorodeoxyglucose fdg avidity liver lesions liver tumor load presence extrahepatic metastases radiological response analyzed results mean 1 7 0 1 gbq 90 y microspheres administered total 16 patients mean age 55 37 17 7 8 males 8 females mean ast alt total bilirubin levels calculated 35 15 40 37 iu l 0 77 0 37 mg dl respectively 6 patients 1 liver lesion determined 2 patients 5 8 patients 5 dimensions varying 12 120 mm liver lesions 13 patients fdg avid mean suvmax 7 4 2 2 extrahepatic metastases demonstrated 5 patients tumor load 4 8 4 patients calculated 25 25 50 50 respectively five patients responsive treatment follow period 243 range 98 839 days 12 patients died cox regression analysis fdg avidity p 0 02 dimensions p 0 03 liver lesion tumor load p 0 02 radiological response p 0 01 found statistically significant parameters predictive overall survival radioembolization p 0 006 conclusion fdg avidity dimension largest liver lesion tumor load radiological response prognostic factors patients receiving radioembolization cholangiocellular carcinoma patients lower tumor load fdg negative tumors smaller tumors seem survive longer radioembolization pubmed","probabilities":0.9799733,"Title":"Radioembolization with (90)Y resin microspheres for intrahepatic cholangiocellular carcinoma: prognostic factors","Abstract":"AIM: To investigate the prognostic factors that predict overall survival after radioembolization in patients with cholangiocellular carcinoma. METHODS: The study comprised 16 patients who received radioembolization with Y(90) resin microspheres for cholangiocarcinoma. The statistical relationships between overall survival after radioembolization and age, number, dimension and fluorodeoxyglucose (FDG) avidity of liver lesions, liver tumor load, presence of extrahepatic metastases, and radiological response were analyzed. RESULTS: Mean 1.7 ± 0.1 GBq(90)Y microspheres were administered to a total of 16 patients (mean age: 55.37 ± 17.7; 8 males, 8 females). Mean AST, ALT, and total bilirubin levels were calculated as 35 ± 15, 40 ± 37 IU/L, and 0.77 ± 0.37 mG/dL, respectively. In 6 patients, 1 liver lesion was determined, in 2 patients ≤ 5, and in 8 patients >5, with dimensions varying between 12 and 120 mm. The liver lesions of 13 patients were FDG avid (mean SUVmax: 7.4 ± 2.2). Extrahepatic metastases were demonstrated in 5 patients. Tumor load of 4, 8, and 4 patients was calculated as <25, 25-50, and >50%, respectively. Five patients were responsive to treatment. During the follow-up period of 243 (range 98-839) days, 12 patients died. In Cox-regression analysis, FDG avidity (p = 0.02), the dimensions (p = 0.03) of the liver lesion, tumor load (p = 0.02), and radiological response (p = 0.01) were found to be statistically significant parameters predictive of overall survival after radioembolization (p = 0.006). CONCLUSION: FDG avidity and the dimension of the largest liver lesion, tumor load, and radiological response are prognostic factors in patients receiving radioembolization for cholangiocellular carcinoma. Patients with lower tumor load, FDG-negative tumors, and smaller tumors seem to survive longer after radioembolization.","Source":"PubMed","category":"HUMAN","training_data":"Radioembolization with (90)Y resin microspheres for intrahepatic cholangiocellular carcinoma: prognostic factors AIM: To investigate the prognostic factors that predict overall survival after radioembolization in patients with cholangiocellular carcinoma. METHODS: The study comprised 16 patients who received radioembolization with Y(90) resin microspheres for cholangiocarcinoma. The statistical relationships between overall survival after radioembolization and age, number, dimension and fluorodeoxyglucose (FDG) avidity of liver lesions, liver tumor load, presence of extrahepatic metastases, and radiological response were analyzed. RESULTS: Mean 1.7 ± 0.1 GBq(90)Y microspheres were administered to a total of 16 patients (mean age: 55.37 ± 17.7; 8 males, 8 females). Mean AST, ALT, and total bilirubin levels were calculated as 35 ± 15, 40 ± 37 IU/L, and 0.77 ± 0.37 mG/dL, respectively. In 6 patients, 1 liver lesion was determined, in 2 patients ≤ 5, and in 8 patients >5, with dimensions varying between 12 and 120 mm. The liver lesions of 13 patients were FDG avid (mean SUVmax: 7.4 ± 2.2). Extrahepatic metastases were demonstrated in 5 patients. Tumor load of 4, 8, and 4 patients was calculated as <25, 25-50, and >50%, respectively. Five patients were responsive to treatment. During the follow-up period of 243 (range 98-839) days, 12 patients died. In Cox-regression analysis, FDG avidity (p = 0.02), the dimensions (p = 0.03) of the liver lesion, tumor load (p = 0.02), and radiological response (p = 0.01) were found to be statistically significant parameters predictive of overall survival after radioembolization (p = 0.006). CONCLUSION: FDG avidity and the dimension of the largest liver lesion, tumor load, and radiological response are prognostic factors in patients receiving radioembolization for cholangiocellular carcinoma. Patients with lower tumor load, FDG-negative tumors, and smaller tumors seem to survive longer after radioembolization. PubMed","prediction_labels":"HUMAN"},{"cleaned":"sorafenib induces cytotoxicity cholangiocarcinoma cell lines inhibiting akt signalling north eastern thailand known prevalence rare cancer called cholangiocarcinoma cca established cancer manifested parasitic liver fluke opisthorchis viverinni infection early stage diagnosis cca difficult tumor advances aggressively limits options suitable treatment sorafenib multikinase inhibitor effectively treats hepatocellular renal thyroid cancers inducing cell death inhibiting cell signaling cca cells speculated respond treatment due upregulated activity receptor tyrosine kinase signaling egfr vegfr known targets sorafenib investigation using mtt assay showed cca cell lines hucca 1 kku 100 kku m055 rbe tfk sensitive 48 hour sorafenib treatment western blot analyses 24 hour sorafenib treatment conducted observe reduced signaling phospho akt increased signaling phospho erk1 2 experiments performed include drug treatments combination clinical standard therapy cisplatin gemcitabine google scholar","probabilities":0.9467213,"Title":"Sorafenib Induces Cytotoxicity In Cholangiocarcinoma Cell Lines By Inhibiting Akt Signalling","Abstract":"North-eastern Thailand is known for its prevalence in a rare cancer called Cholangiocarcinoma (CCA). It has been established that the cancer\nis manifested from parasitic liver-fluke Opisthorchis viverinni infection. Early stage diagnosis for CCA is difficult until the tumor advances\naggressively. This limits the options for suitable treatment. Sorafenib, a multikinase inhibitor, effectively treats hepatocellular, renal and\nthyroid cancers, by inducing cell death by inhibiting cell signaling. CCA cells were speculated to respond to this treatment due to their\nupregulated activity of receptor tyrosine kinase signaling, such as EGFR and VEGFR, which are known targets of Sorafenib. In this\ninvestigation, using MTT assay, we showed CCA cell lines, HuCCA-1, KKU-100, KKU-M055, RBE and TFK, were sensitive to 48-hour Sorafenib\ntreatment. Western Blot analyses with 24-hour Sorafenib treatment were conducted to observe reduced signaling of phospho-Akt and\nincreased signaling of phospho-ERK1/2. Further experiments will be performed to include drug treatments in combination with clinical\nstandard therapy Cisplatin and Gemcitabine","Source":"Google Scholar","category":"ANIMAL","training_data":"Sorafenib Induces Cytotoxicity In Cholangiocarcinoma Cell Lines By Inhibiting Akt Signalling North-eastern Thailand is known for its prevalence in a rare cancer called Cholangiocarcinoma (CCA). It has been established that the cancer\nis manifested from parasitic liver-fluke Opisthorchis viverinni infection. Early stage diagnosis for CCA is difficult until the tumor advances\naggressively. This limits the options for suitable treatment. Sorafenib, a multikinase inhibitor, effectively treats hepatocellular, renal and\nthyroid cancers, by inducing cell death by inhibiting cell signaling. CCA cells were speculated to respond to this treatment due to their\nupregulated activity of receptor tyrosine kinase signaling, such as EGFR and VEGFR, which are known targets of Sorafenib. In this\ninvestigation, using MTT assay, we showed CCA cell lines, HuCCA-1, KKU-100, KKU-M055, RBE and TFK, were sensitive to 48-hour Sorafenib\ntreatment. Western Blot analyses with 24-hour Sorafenib treatment were conducted to observe reduced signaling of phospho-Akt and\nincreased signaling of phospho-ERK1/2. Further experiments will be performed to include drug treatments in combination with clinical\nstandard therapy Cisplatin and Gemcitabine Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"global trends intrahepatic extrahepatic cholangiocarcinoma incidence 1993 2012 background intrahepatic cholangiocarcinomas iccs extrahepatic cholangiocarcinomas eccs highly lethal bile duct tumors incidence difficult estimate changes cancer coding time studies date examined global incidence trends high quality topography histology specific cancer registry data therefore study examined icc ecc incidence cancer incidence five continents plus database methods regional national cancer registry data used estimate age standardized incidence rates asrs per 100 000 person years 95 confidence intervals average annual percent changes aapcs icc 38 countries ecc 33 countries 1993 2012 icc ecc trends tabulated plotted country rates versus birth cohort age plotted age period cohort analysis performed assess age cohort incidence rate ratios results highest rates icc ecc asia specifically south korea asr icc 2 80 asr ecc 2 24 thailand asr icc 2 19 asr ecc 0 71 japan asr icc 0 95 asr ecc 0 83 1993 2012 incidence rates icc ecc increased countries largest asr increases study period occurred latvia aapc 20 1 china aapc 11 1 icc thailand aapc 8 8 colombia aapc 8 5 ecc conclusions 20 years examined icc ecc incidence increased majority countries worldwide icc ecc incidence may continue increase metabolic infectious etiologic factors efforts elucidate risk factors contributing increases incidence warranted stn","probabilities":0.9799733,"Title":"Global Trends In Intrahepatic And Extrahepatic Cholangiocarcinoma Incidence From 1993 To 2012","Abstract":"Background: Intrahepatic cholangiocarcinomas (ICCs) and extrahepatic cholangiocarcinomas (ECCs) are highly lethal bile duct tumors. Their incidence can be difficult to estimate because of changes in cancer coding over time. No studies to date have examined their global incidence and trends with high-quality topography- and histology-specific cancer registry data. Therefore, this study examined ICC and ECC incidence with the Cancer Incidence in Five Continents Plus database. \r\n\r\n Methods: Regional and national cancer registry data were used to estimate age-standardized incidence rates (ASRs) per 100,000 person-years, 95% confidence intervals, and average annual percent changes (AAPCs) for ICC in 38 countries and for ECC in 33 countries from 1993 to 2012. ICC and ECC trends were tabulated and plotted by country. Rates versus birth cohort by age were plotted, and an age-period-cohort analysis was performed to assess age and cohort incidence rate ratios. \r\n\r\n Results: The highest rates of ICC and ECC were in Asia, specifically South Korea (ASR for ICC, 2.80; ASR for ECC, 2.24), Thailand (ASR for ICC, 2.19; ASR for ECC, 0.71), and Japan (ASR for ICC, 0.95; ASR for ECC, 0.83). Between 1993 and 2012, incidence rates of both ICC and ECC increased in most countries. The largest ASR increases over the study period occurred in Latvia (AAPC, 20.1%) and China (AAPC, 11.1%) for ICC and in Thailand (AAPC, 8.8%) and Colombia (AAPC, 8.5%) for ECC. \r\n\r\n Conclusions: In the 20 years examined, ICC and ECC incidence increased in the majority of countries worldwide. ICC and ECC incidence may continue to increase because of metabolic and infectious etiologic factors. Efforts to further elucidate risk factors contributing to these increases in incidence are warranted.","Source":"STN","category":"HUMAN","training_data":"Global Trends In Intrahepatic And Extrahepatic Cholangiocarcinoma Incidence From 1993 To 2012 Background: Intrahepatic cholangiocarcinomas (ICCs) and extrahepatic cholangiocarcinomas (ECCs) are highly lethal bile duct tumors. Their incidence can be difficult to estimate because of changes in cancer coding over time. No studies to date have examined their global incidence and trends with high-quality topography- and histology-specific cancer registry data. Therefore, this study examined ICC and ECC incidence with the Cancer Incidence in Five Continents Plus database. \r\n\r\n Methods: Regional and national cancer registry data were used to estimate age-standardized incidence rates (ASRs) per 100,000 person-years, 95% confidence intervals, and average annual percent changes (AAPCs) for ICC in 38 countries and for ECC in 33 countries from 1993 to 2012. ICC and ECC trends were tabulated and plotted by country. Rates versus birth cohort by age were plotted, and an age-period-cohort analysis was performed to assess age and cohort incidence rate ratios. \r\n\r\n Results: The highest rates of ICC and ECC were in Asia, specifically South Korea (ASR for ICC, 2.80; ASR for ECC, 2.24), Thailand (ASR for ICC, 2.19; ASR for ECC, 0.71), and Japan (ASR for ICC, 0.95; ASR for ECC, 0.83). Between 1993 and 2012, incidence rates of both ICC and ECC increased in most countries. The largest ASR increases over the study period occurred in Latvia (AAPC, 20.1%) and China (AAPC, 11.1%) for ICC and in Thailand (AAPC, 8.8%) and Colombia (AAPC, 8.5%) for ECC. \r\n\r\n Conclusions: In the 20 years examined, ICC and ECC incidence increased in the majority of countries worldwide. ICC and ECC incidence may continue to increase because of metabolic and infectious etiologic factors. Efforts to further elucidate risk factors contributing to these increases in incidence are warranted. STN","prediction_labels":"HUMAN"},{"cleaned":"tgf signaling effective target impair survival induce apoptosis human cholangiocarcinoma cells study human primary cell cultures cholangiocarcinoma cca subtypes mucin mixed cca arise neoplastic transformation cholangiocytes epithelial cells lining biliary tree cca high mortality rate owing aggressiveness late diagnosis high resistance radiotherapy chemotherapeutics demonstrated cca enriched cancer stem cells express epithelial mesenchymal transition emt traits features associated aggressiveness drug resistance tgf signaling upregulated cca involved emt recently established primary cell cultures human mucin mixed intrahepatic cca human cca primary cultures different levels emt trait expression evaluated anticancer effects cx 4945 casein kinase 2 ck2 inhibitor blocks tgf 1 induced emt ii ly2157299 tgf receptor kinase inhibitor tested primary cell lines expressing emt trait markers vimentin n cadherin nuclear catenin negative epithelial markers cell lines expressing epithelial markers ck19 positive association emt traits cell viability evaluated mts assays apoptosis annexin v fitc cell migration wound healing assay results dose 10 m cx4945 significantly decreased cell viability primary human cell cultures mucin mixed cca whereas ck19 positive cell cultures effect cx4945 cell viability required higher concentrations 30 m concentrations cx4945 also induced apoptosis 3 fold increase vs controls correlated expression level ck2 different cca cell lines mucin mixed cca indeed apoptotic effects observed ck19 positive cells expressing lower ck2 levels effects cx4945 viability apoptosis associated increased number h2ax biomarker dna double strand breaks foci suggesting active role ck2 repair mechanism ccas ly2157299 failed influence cell proliferation apoptosis significantly inhibited cell migration 50 m concentration fact ly2157299 significantly impaired 24 48 120 hrs wound healing primary cell cultures mucin mixed cca conclusion demonstrated cx4945 ly2157299 exert relevant distinct anticancer effects human cca cells cx4945 acting cell viability apoptosis ly2157299 impairing cell migration results suggest targeting tgf signaling combination cx 4945 ly2157299 potential benefits treatment human cca stn","probabilities":1.0,"Title":"Tgf-ß Signaling Is An Effective Target To Impair Survival And Induce Apoptosis Of Human Cholangiocarcinoma Cells: A Study On Human Primary Cell Cultures","Abstract":"Cholangiocarcinoma (CCA) and its subtypes (mucin- and mixed-CCA) arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT) traits, with these features being associated with aggressiveness and drug resistance. TGF-β signaling is upregulated in CCA and involved in EMT. We have recently established primary cell cultures from human mucin- and mixed-intrahepatic CCA. In human CCA primary cultures with different levels of EMT trait expression, we evaluated the anticancer effects of: (i) CX-4945, a casein kinase-2 (CK2) inhibitor that blocks TGF-β1-induced EMT; and (ii) LY2157299, a TGF-β receptor I kinase inhibitor. We tested primary cell lines expressing EMT trait markers (vimentin, N-cadherin and nuclear catenin) but negative for epithelial markers, and cell lines expressing epithelial markers (CK19-positive) in association with EMT traits. Cell viability was evaluated by MTS assays, apoptosis by Annexin V FITC and cell migration by wound-healing assay. \r\n\r\n Results: at a dose of 10 μM, CX4945 significantly decreased cell viability of primary human cell cultures from both mucin and mixed CCA, whereas in CK19-positive cell cultures, the effect of CX4945 on cell viability required higher concentrations (>30μM). At the same concentrations, CX4945 also induced apoptosis (3- fold increase vs controls) which correlated with the expression level of CK2 in the different CCA cell lines (mucin- and mixed-CCA). Indeed, no apoptotic effects were observed in CK19-positive cells expressing lower CK2 levels. The effects of CX4945 on viability and apoptosis were associated with an increased number of γ-H2ax (biomarker for DNA double-strand breaks) foci, suggesting the active role of CK2 as a repair mechanism in CCAs. LY2157299 failed to influence cell proliferation or apoptosis but significantly inhibited cell migration. At a 50 μM concentration, in fact, LY2157299 significantly impaired (at 24, 48 and 120 hrs) the wound-healing of primary cell cultures from both mucin-and mixed-CCA. In conclusion, we demonstrated that CX4945 and LY2157299 exert relevant but distinct anticancer effects against human CCA cells, with CX4945 acting on cell viability and apoptosis, and LY2157299 impairing cell migration. These results suggest that targeting the TGF-β signaling with a combination of CX-4945 and LY2157299 could have potential benefits in the treatment of human CCA.","Source":"STN","category":"ANIMAL","training_data":"Tgf-ß Signaling Is An Effective Target To Impair Survival And Induce Apoptosis Of Human Cholangiocarcinoma Cells: A Study On Human Primary Cell Cultures Cholangiocarcinoma (CCA) and its subtypes (mucin- and mixed-CCA) arise from the neoplastic transformation of cholangiocytes, the epithelial cells lining the biliary tree. CCA has a high mortality rate owing to its aggressiveness, late diagnosis and high resistance to radiotherapy and chemotherapeutics. We have demonstrated that CCA is enriched for cancer stem cells which express epithelial to mesenchymal transition (EMT) traits, with these features being associated with aggressiveness and drug resistance. TGF-β signaling is upregulated in CCA and involved in EMT. We have recently established primary cell cultures from human mucin- and mixed-intrahepatic CCA. In human CCA primary cultures with different levels of EMT trait expression, we evaluated the anticancer effects of: (i) CX-4945, a casein kinase-2 (CK2) inhibitor that blocks TGF-β1-induced EMT; and (ii) LY2157299, a TGF-β receptor I kinase inhibitor. We tested primary cell lines expressing EMT trait markers (vimentin, N-cadherin and nuclear catenin) but negative for epithelial markers, and cell lines expressing epithelial markers (CK19-positive) in association with EMT traits. Cell viability was evaluated by MTS assays, apoptosis by Annexin V FITC and cell migration by wound-healing assay. \r\n\r\n Results: at a dose of 10 μM, CX4945 significantly decreased cell viability of primary human cell cultures from both mucin and mixed CCA, whereas in CK19-positive cell cultures, the effect of CX4945 on cell viability required higher concentrations (>30μM). At the same concentrations, CX4945 also induced apoptosis (3- fold increase vs controls) which correlated with the expression level of CK2 in the different CCA cell lines (mucin- and mixed-CCA). Indeed, no apoptotic effects were observed in CK19-positive cells expressing lower CK2 levels. The effects of CX4945 on viability and apoptosis were associated with an increased number of γ-H2ax (biomarker for DNA double-strand breaks) foci, suggesting the active role of CK2 as a repair mechanism in CCAs. LY2157299 failed to influence cell proliferation or apoptosis but significantly inhibited cell migration. At a 50 μM concentration, in fact, LY2157299 significantly impaired (at 24, 48 and 120 hrs) the wound-healing of primary cell cultures from both mucin-and mixed-CCA. In conclusion, we demonstrated that CX4945 and LY2157299 exert relevant but distinct anticancer effects against human CCA cells, with CX4945 acting on cell viability and apoptosis, and LY2157299 impairing cell migration. These results suggest that targeting the TGF-β signaling with a combination of CX-4945 and LY2157299 could have potential benefits in the treatment of human CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"elevated aqp1 expression associated unfavorable oncologic outcome patients hilar cholangiocarcinoma background hilar cholangiocarcinomas malignant tumors poor prognosis early prediction prognosis patients may help us determine treatment strategies aquaporin 1 cell membrane channel involved water transport cell motility proliferation increasing evidences showed aquaporin 1 played role tumor prognosis diagnosis purpose study evaluate role aquaporin 1 hilar cholangiocarcinoma methods analyzed messenger rna expression data genes function bile secretion data set 169 samples using r2 bioinformatic platform http r2 amc nl quantitative polymerase chain reaction performed verify gene expression 17 hilar cholangiocarcinoma samples immunohistochemistry also performed series specimens 62 hilar cholangiocarcinoma tissues clinical significance assessed clinical correlation kaplan meier analyses results data analyzed using r2 web application aquaporin 1 selected analysis significant expression variation aquaporin 1 among 17 cases cholangiocarcinoma also found using quantitative polymerase chain reaction expression level aquaporin 1 protein significantly correlated tumor node metastasis stage p 002 overall survival time p 010 higher aquaporin 1 expression indicated poor prognostic outcomes p 05 log rank test multivariate analysis also showed strong aquaporin 1 protein expression independent adverse prognosticator hilar cholangiocarcinoma p 002 conclusion study highlighted prognostic value aquaporin 1 hilar cholangiocarcinoma strong aquaporin 1 expression predicts poor survival regardless pathological features immunohistochemical detection aquaporin 1 prognostic marker may contribute predicting clinical outcome patients hilar cholangiocarcinoma stn","probabilities":0.54545456,"Title":"Elevated Aqp1 Expression Is Associated With Unfavorable Oncologic Outcome In Patients With Hilar Cholangiocarcinoma","Abstract":"Background: Hilar cholangiocarcinomas are malignant tumors with a poor prognosis. An early prediction of prognosis for patients may help us determine treatment strategies. Aquaporin 1 is a cell membrane channel involved in water transport, cell motility, and proliferation. Increasing evidences showed that aquaporin 1 played a role in tumor prognosis and diagnosis. The purpose of this study is to evaluate the role of aquaporin 1 in hilar cholangiocarcinoma. \r\n\r\n Methods: Here, we analyzed messenger RNA expression data of genes function as bile secretion in a data set of 169 samples using the R2 bioinformatic platform ( http://r2.amc.nl ). Quantitative polymerase chain reaction was performed to verify the gene expression in 17 hilar cholangiocarcinoma samples. Immunohistochemistry was also performed in a series of specimens from 62 hilar cholangiocarcinoma tissues, and its clinical significance was assessed by clinical correlation and Kaplan-Meier analyses. \r\n\r\n Results: All data were analyzed using the R2 web application, aquaporin 1 was selected for further analysis. The significant expression variation of aquaporin 1 among 17 cases with cholangiocarcinoma was also found using quantitative polymerase chain reaction. The expression level of aquaporin 1 protein significantly correlated with tumor-node-metastasis stage ( P = .002) and overall survival time ( P = .010). Higher aquaporin 1 expression indicated poor prognostic outcomes ( P <.05, log-rank test). Multivariate analysis also showed strong aquaporin 1 protein expression was an independent adverse prognosticator in hilar cholangiocarcinoma ( P = .002). \r\n\r\n Conclusion: This study highlighted the prognostic value of aquaporin 1 in hilar cholangiocarcinoma. Strong aquaporin 1 expression predicts poor survival, regardless of pathological features. Immunohistochemical detection of aquaporin 1, as a prognostic marker, may contribute to predicting clinical outcome for patients with hilar cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Elevated Aqp1 Expression Is Associated With Unfavorable Oncologic Outcome In Patients With Hilar Cholangiocarcinoma Background: Hilar cholangiocarcinomas are malignant tumors with a poor prognosis. An early prediction of prognosis for patients may help us determine treatment strategies. Aquaporin 1 is a cell membrane channel involved in water transport, cell motility, and proliferation. Increasing evidences showed that aquaporin 1 played a role in tumor prognosis and diagnosis. The purpose of this study is to evaluate the role of aquaporin 1 in hilar cholangiocarcinoma. \r\n\r\n Methods: Here, we analyzed messenger RNA expression data of genes function as bile secretion in a data set of 169 samples using the R2 bioinformatic platform ( http://r2.amc.nl ). Quantitative polymerase chain reaction was performed to verify the gene expression in 17 hilar cholangiocarcinoma samples. Immunohistochemistry was also performed in a series of specimens from 62 hilar cholangiocarcinoma tissues, and its clinical significance was assessed by clinical correlation and Kaplan-Meier analyses. \r\n\r\n Results: All data were analyzed using the R2 web application, aquaporin 1 was selected for further analysis. The significant expression variation of aquaporin 1 among 17 cases with cholangiocarcinoma was also found using quantitative polymerase chain reaction. The expression level of aquaporin 1 protein significantly correlated with tumor-node-metastasis stage ( P = .002) and overall survival time ( P = .010). Higher aquaporin 1 expression indicated poor prognostic outcomes ( P <.05, log-rank test). Multivariate analysis also showed strong aquaporin 1 protein expression was an independent adverse prognosticator in hilar cholangiocarcinoma ( P = .002). \r\n\r\n Conclusion: This study highlighted the prognostic value of aquaporin 1 in hilar cholangiocarcinoma. Strong aquaporin 1 expression predicts poor survival, regardless of pathological features. Immunohistochemical detection of aquaporin 1, as a prognostic marker, may contribute to predicting clinical outcome for patients with hilar cholangiocarcinoma. STN","prediction_labels":"HUMAN"},{"cleaned":"biliary tract cancers epidemiology molecular pathogenesis genetic risk associations biliary tract cancers btc malignancies arise epithelium biliary system comprise second common type hepatobiliary cancer worldwide btc sub classified intrahepatic cholangiocarcinoma icca perhilar hilar cholangiocarcinoma pcca distal cholangiocarcinoma dcca gallbladder carcinoma due differences etiologic risk factors pathogenesis molecular genetic characteristics subtypes considered separate biological entity geographic diversity risk factors subtypes biliary cancers results profound differences worldwide incidence article provide review current epidemiology btc associated risk factors discuss available evidence genetic predisposition btc anticipate results planned large scale genome wide association studies gwas exploring inherited sequence variants conferring risk btc studies may also potentially reveal important pathogenic mechanisms biliary tract cancer subtypes pubmed","probabilities":0.9799733,"Title":"Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations","Abstract":"Biliary tract cancers (BTC) are malignancies that arise from the epithelium of the biliary system and comprise the second most common type of hepatobiliary cancer worldwide. BTC are sub-classified as intrahepatic cholangiocarcinoma (iCCA), perhilar/hilar cholangiocarcinoma (pCCA), distal cholangiocarcinoma (dCCA), and gallbladder carcinoma. Due to the differences in their etiologic risk factors, pathogenesis, and molecular and genetic characteristics, each of these subtypes is considered a separate biological entity. The geographic diversity of risk factors for the subtypes of biliary cancers results in profound differences in the worldwide incidence of each. In this article we provide a review of the current epidemiology of BTC and their associated risk factors. Further, we discuss the available evidence for genetic predisposition to BTC and anticipate the results of planned large-scale, genome-wide association studies (GWAS) exploring the inherited sequence variants conferring risk of BTC. These studies may also potentially of reveal important pathogenic mechanisms of the biliary tract cancer subtypes.","Source":"PubMed","category":"HUMAN","training_data":"Biliary tract cancers: epidemiology, molecular pathogenesis and genetic risk associations Biliary tract cancers (BTC) are malignancies that arise from the epithelium of the biliary system and comprise the second most common type of hepatobiliary cancer worldwide. BTC are sub-classified as intrahepatic cholangiocarcinoma (iCCA), perhilar/hilar cholangiocarcinoma (pCCA), distal cholangiocarcinoma (dCCA), and gallbladder carcinoma. Due to the differences in their etiologic risk factors, pathogenesis, and molecular and genetic characteristics, each of these subtypes is considered a separate biological entity. The geographic diversity of risk factors for the subtypes of biliary cancers results in profound differences in the worldwide incidence of each. In this article we provide a review of the current epidemiology of BTC and their associated risk factors. Further, we discuss the available evidence for genetic predisposition to BTC and anticipate the results of planned large-scale, genome-wide association studies (GWAS) exploring the inherited sequence variants conferring risk of BTC. These studies may also potentially of reveal important pathogenic mechanisms of the biliary tract cancer subtypes. PubMed","prediction_labels":"HUMAN"},{"cleaned":"treatment outcomes prognostic factors intrahepatic cholangiocarcinoma single center experience aim determine treatment outcome prognostic factors survival patients peripheral intrahepatic cholangiocarcinoma icc methods data collected retrospective chart review patients diagnosed icc 2000 2010 single institution calculated survival rates prognostic factors survival results total 105 patients identified icc among 63 8 67 105 older 60 yrs 50 5 53 205 male 88 6 93 105 caucasian icc commonly presented abdominal pain 34 3 found incidentally imaging studies 30 5 32 105 tumor developed de novo majority patients 82 9 87 105 9 5 10 105 cirrhosis 6 7 7 105 psc uc preoperative imaging showed single lesion patients multifocal lesions 17 1 18 105 surgical resection performed 50 5 53 105 patients resection 17 0 9 53 positive margins 24 5 13 53 positive nodes 39 6 21 53 adjuvant chemoradiotherapy tumor recurrence occurred 45 3 24 53 contrast 49 5 52 105 unresectable due metastatic disease 57 local tumor invasion 29 co morbidities 12 chemoradiotherapy transarterial chemoembolization used palliative treatments 53 8 28 52 7 7 4 52 patients unresectable icc theremaining patients23 0 12 52 undergotreatment themedian survival rates 16 1 months 95 ci 13 1 19 2 entire cohort 27 6 months 95 ci 17 6 37 6 forresection 12 87months 6 51 19 23months forpalliativechemoradiotherapy 4 99 months 0 36 9 62 treatment p 0 001 tumor stage diagnosis p 0 001 bilirubin 2 mg dl 0 032 presence metastases diagnosis 0 008 nature treatment received p 0 001 found significant predictors survival onunivariateanalysis age p 0 292 gender p 0 822 ethnicity p 0 141 albumin 3gm dl 0 887 underlying risk factor 0 659 elevated ca19 9 0 911 found associated survival multivariate analysis advanced stage diagnosis p 0 027 treatment received 0 001 significantly independently associated survival patients underwent resection advanced ajcc stage p 0 007 presence microvascular invasion p 0 013 found significant independent predictors poor survival conclusion surgical resection offers optimal treatment outcomeinpatientswithicc stageatdiagnosisisasignificantprognosticfactorindependent treatment received google scholar","probabilities":0.9799733,"Title":"Treatment Outcomes And Prognostic Factors For Intrahepatic Cholangiocarcinoma Single Center Experience","Abstract":"Aim: To determine the treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC). Methods: Data were collected by retrospective chart review of patients diagnosed with ICC between 2000 and 2010 at a single institution. We calculated survival rates and prognostic factors for survival. Results: A total of 105 patients were identified with ICC. Among them, 63.8% (67/105) were older than 60 yrs, 50.5% (53/205) were male and 88.6% (93/105) were Caucasian. ICC most commonly presented with abdominal pain (34.3%) but was found incidentally on imaging studies in 30.5% (32/105). While the tumor developed de novo in the majority of patients 82.9% (87/105), 9.5% (10/105) had cirrhosis and 6.7% (7/105) had PSC/UC. Preoperative imaging showed a single lesion in most patients and multifocal lesions in 17.1% (18/105). Surgical resection was performed in 50.5% (53/105 patients). After resection 17.0% (9/53) had positive margins, 24.5% (13/53) had positive nodes and 39.6% (21/53) had adjuvant chemoradiotherapy. Tumor recurrence occurred in 45.3% (24/53). In contrast, 49.5% (52/ 105) were unresectable due to metastatic disease (57%), local tumor invasion (29%) and co-morbidities (12%). Chemoradiotherapy and transarterial chemoembolization were used as palliative treatments in 53.8% (28/52) and 7.7% (4/52) of patients with unresectable ICC while theremaining patients23.0% (12/52)did not undergotreatment. Themedian survival rates were 16.1 months (95% CI 13.1-19.2) for the entire cohort, 27.6 months (95% CI 17.6-37.6)forresection,12.87months(6.51-19.23months)forpalliativechemoradiotherapy and it was 4.99 months (0.36-9.62) for no treatment (p=0.001). Tumor stage at diagnosis (p<0.001), bilirubin >2 mg/dl (0.032), presence of metastases at diagnosis (0.008) and nature of treatment received (p<0.001) were found to be significant predictors of survival onunivariateanalysis.Age(p=0.292),gender(p=0.822),ethnicity(p=0.141),albumin<3gm/ dl (0.887), underlying risk factor (0.659), and elevated CA19-9 (0.911) were not found to associated with survival. Further, on multivariate analysis advanced stage at diagnosis (p= 0.027) and treatment received (<0.001) were significantly and independently associated with survival. In patients who underwent resection advanced AJCC stage (p=0.007) and presence of microvascular invasion (p=0.013) were found to be significant and independent predictors of poor survival Conclusion: Surgical resection offers the optimal treatment outcomeinpatientswithICC.Stageatdiagnosisisasignificantprognosticfactorindependent of the treatment received","Source":"Google Scholar","category":"HUMAN","training_data":"Treatment Outcomes And Prognostic Factors For Intrahepatic Cholangiocarcinoma Single Center Experience Aim: To determine the treatment outcome and prognostic factors for survival in patients with peripheral intrahepatic cholangiocarcinoma (ICC). Methods: Data were collected by retrospective chart review of patients diagnosed with ICC between 2000 and 2010 at a single institution. We calculated survival rates and prognostic factors for survival. Results: A total of 105 patients were identified with ICC. Among them, 63.8% (67/105) were older than 60 yrs, 50.5% (53/205) were male and 88.6% (93/105) were Caucasian. ICC most commonly presented with abdominal pain (34.3%) but was found incidentally on imaging studies in 30.5% (32/105). While the tumor developed de novo in the majority of patients 82.9% (87/105), 9.5% (10/105) had cirrhosis and 6.7% (7/105) had PSC/UC. Preoperative imaging showed a single lesion in most patients and multifocal lesions in 17.1% (18/105). Surgical resection was performed in 50.5% (53/105 patients). After resection 17.0% (9/53) had positive margins, 24.5% (13/53) had positive nodes and 39.6% (21/53) had adjuvant chemoradiotherapy. Tumor recurrence occurred in 45.3% (24/53). In contrast, 49.5% (52/ 105) were unresectable due to metastatic disease (57%), local tumor invasion (29%) and co-morbidities (12%). Chemoradiotherapy and transarterial chemoembolization were used as palliative treatments in 53.8% (28/52) and 7.7% (4/52) of patients with unresectable ICC while theremaining patients23.0% (12/52)did not undergotreatment. Themedian survival rates were 16.1 months (95% CI 13.1-19.2) for the entire cohort, 27.6 months (95% CI 17.6-37.6)forresection,12.87months(6.51-19.23months)forpalliativechemoradiotherapy and it was 4.99 months (0.36-9.62) for no treatment (p=0.001). Tumor stage at diagnosis (p<0.001), bilirubin >2 mg/dl (0.032), presence of metastases at diagnosis (0.008) and nature of treatment received (p<0.001) were found to be significant predictors of survival onunivariateanalysis.Age(p=0.292),gender(p=0.822),ethnicity(p=0.141),albumin<3gm/ dl (0.887), underlying risk factor (0.659), and elevated CA19-9 (0.911) were not found to associated with survival. Further, on multivariate analysis advanced stage at diagnosis (p= 0.027) and treatment received (<0.001) were significantly and independently associated with survival. In patients who underwent resection advanced AJCC stage (p=0.007) and presence of microvascular invasion (p=0.013) were found to be significant and independent predictors of poor survival Conclusion: Surgical resection offers the optimal treatment outcomeinpatientswithICC.Stageatdiagnosisisasignificantprognosticfactorindependent of the treatment received Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma clinical presentation management survival analysis abstract available google scholar","probabilities":0.9799733,"Title":"Cholangiocarcinoma Clinical Presentation Management And Survival Analysis","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Cholangiocarcinoma Clinical Presentation Management And Survival Analysis Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"adjuvant chemotherapy radiation therapy improves survival patients extrahepatic cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Adjuvant Chemotherapy And Radiation Therapy Improves Survival For Patients With Extrahepatic Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Adjuvant Chemotherapy And Radiation Therapy Improves Survival For Patients With Extrahepatic Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"gns561 alone combination cisplatin gemcitabine treatment intrahepatic cholangiocarcinoma abstract available google scholar","probabilities":0.9799733,"Title":"Gns561 Alone Or In Combination With Cisplatin Or Gemcitabine For The Treatment Of Intrahepatic Cholangiocarcinoma","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"Gns561 Alone Or In Combination With Cisplatin Or Gemcitabine For The Treatment Of Intrahepatic Cholangiocarcinoma Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"site specific metastases intrahepatic cholangiocarcinoma impact survival population based study aim limited data exist impact metastatic sites survival patients metastatic intrahepatic cholangiocarcinoma icc methods patients metastatic icc identified seer 2010 2015 results total 981 patients identified population liver 57 9 common site icc metastases followed lung bone brain respective median overall survival cancer specific survival 6 9 months entire population analysis suggested patients treated surgery primary metastatic lesions better survival outcome patients surgery p 0 001 conclusion liver common site icc metastases local treatment surgery primary metastatic lesions obviously benefit patients stn","probabilities":0.9799733,"Title":"Site-Specific Metastases Of Intrahepatic Cholangiocarcinoma And Its Impact On Survival: A Population-Based Study","Abstract":"Aim: Limited data exist on impact of the metastatic sites on survival in patients with metastatic intrahepatic cholangiocarcinoma (ICC). Methods: Patients with metastatic ICC were identified in the SEER from 2010 to 2015. Results: A total of 981 patients were identified, of this population, liver (57.9%) is the most common site of ICC metastases, followed by lung, bone and brain. Respective median overall survival and cancer-specific survival were 6 and 9 months in entire population. Further analysis suggested that patients treated by surgery to primary and/or metastatic lesions had a better survival outcome than patients had no surgery (p ≤ 0.001). Conclusion: Liver is the most common site for ICC metastases, local treatment such as surgery to primary or metastatic lesions obviously benefit patients.","Source":"STN","category":"HUMAN","training_data":"Site-Specific Metastases Of Intrahepatic Cholangiocarcinoma And Its Impact On Survival: A Population-Based Study Aim: Limited data exist on impact of the metastatic sites on survival in patients with metastatic intrahepatic cholangiocarcinoma (ICC). Methods: Patients with metastatic ICC were identified in the SEER from 2010 to 2015. Results: A total of 981 patients were identified, of this population, liver (57.9%) is the most common site of ICC metastases, followed by lung, bone and brain. Respective median overall survival and cancer-specific survival were 6 and 9 months in entire population. Further analysis suggested that patients treated by surgery to primary and/or metastatic lesions had a better survival outcome than patients had no surgery (p ≤ 0.001). Conclusion: Liver is the most common site for ICC metastases, local treatment such as surgery to primary or metastatic lesions obviously benefit patients. STN","prediction_labels":"HUMAN"},{"cleaned":"biweekly cisplatin gemcitabine patients advanced biliary tract cancer treatment cisplatin gemcitabine demonstrates survival benefit patients advanced biliary tract cancer abtc however weekly administration add significant toxicities may prohibit prolonged treatment based previous studies implemented modified biweekly regimen gc attempt optimize prescribed regimen improved toxicity profile added convenience patients maintaining efficacy patients abtc treated fixed dose rate fdr gemcitabine 1 000 mg m 2 min cisplatin 20 mg m 2 days 1 15 every 28 day cycle patients received treatment time progression death discontinuation due intolerance collected data included demographics clinico pathologic features toxicities survival kaplan meier curves used calculate median overall survival os progression free survival pfs study included 107 evaluable pts unresectable abtc received biweekly regimen sites tumor included gallbladder 21 5 ampullary 3 7 bile duct 74 8 median number cycles 6 1 27 median pfs 8 34 6 74 9 23 months median os 10 32 9 10 11 43 months common grade 3 adverse events included neutropenia 11 fatigue 10 thrombocytopenia 6 4 biweekly fdr gc abtc associated favorable toxicity profile maintaining efficacy similar observed prior clinical trials minimal toxicities observed despite prolonged course many patients prospective trials consider evaluating role biweekly gc regimen abtc including potentially favorable platform novel experimental strategies pubmed","probabilities":0.9799733,"Title":"Biweekly cisplatin and gemcitabine in patients with advanced biliary tract cancer","Abstract":"Treatment with cisplatin and gemcitabine demonstrates a survival benefit in patients with advanced biliary tract cancer (ABTC). However, the weekly administration can add significant toxicities that may prohibit prolonged treatment. Based on previous studies, we implemented a modified biweekly regimen of GC in an attempt to optimize the prescribed regimen with an improved toxicity profile, added convenience to patients while maintaining efficacy. Patients with ABTC were treated with fixed dose rate (FDR) gemcitabine (1,000 mg/m(2) /min) and cisplatin 20 mg/m(2) on days 1 and 15 of every 28-day cycle. Patients received treatment until time of progression, death, or discontinuation due to intolerance. Collected data included demographics, clinico-pathologic features, toxicities, and survival. Kaplan-Meier curves were used to calculate the median overall survival (OS) and progression free survival (PFS). The study included 107 evaluable pts with unresectable ABTC who received the biweekly regimen. Sites of tumor included gallbladder (21.5%), ampullary (3.7%), and bile duct (74.8%). Median number of cycles was 6 (1-27). Median PFS was 8.34 (6.74, 9.23) months and median OS was 10.32 (9.10, 11.43) months. Most common grade ≥3 adverse events included neutropenia (11%), fatigue (10%), and thrombocytopenia (6.4%). Biweekly FDR GC in ABTC is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in prior clinical trials. Minimal toxicities were observed despite a prolonged course for many patients. Further prospective trials should consider evaluating the role of biweekly GC regimen in ABTC, including a potentially more favorable platform in novel experimental strategies.","Source":"PubMed","category":"HUMAN","training_data":"Biweekly cisplatin and gemcitabine in patients with advanced biliary tract cancer Treatment with cisplatin and gemcitabine demonstrates a survival benefit in patients with advanced biliary tract cancer (ABTC). However, the weekly administration can add significant toxicities that may prohibit prolonged treatment. Based on previous studies, we implemented a modified biweekly regimen of GC in an attempt to optimize the prescribed regimen with an improved toxicity profile, added convenience to patients while maintaining efficacy. Patients with ABTC were treated with fixed dose rate (FDR) gemcitabine (1,000 mg/m(2) /min) and cisplatin 20 mg/m(2) on days 1 and 15 of every 28-day cycle. Patients received treatment until time of progression, death, or discontinuation due to intolerance. Collected data included demographics, clinico-pathologic features, toxicities, and survival. Kaplan-Meier curves were used to calculate the median overall survival (OS) and progression free survival (PFS). The study included 107 evaluable pts with unresectable ABTC who received the biweekly regimen. Sites of tumor included gallbladder (21.5%), ampullary (3.7%), and bile duct (74.8%). Median number of cycles was 6 (1-27). Median PFS was 8.34 (6.74, 9.23) months and median OS was 10.32 (9.10, 11.43) months. Most common grade ≥3 adverse events included neutropenia (11%), fatigue (10%), and thrombocytopenia (6.4%). Biweekly FDR GC in ABTC is associated with a more favorable toxicity profile while maintaining efficacy similar to that observed in prior clinical trials. Minimal toxicities were observed despite a prolonged course for many patients. Further prospective trials should consider evaluating the role of biweekly GC regimen in ABTC, including a potentially more favorable platform in novel experimental strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cholangiocarcinoma treatment outcomes nutrition overview oncology nurses background cholangiocarcinoma cancer arises bile ducts inside outside liver although rare cancer cholangiocarcinoma appears rising incidence united states worldwide objectives diagnosis cholangiocarcinoma frequently presents biliary emergencies diagnosis treatment lethality cancer stems part challenges supportive care treatment article provides overview intrahepatic extrahepatic cholangiocarcinoma including identification risk factors differences treatment approaches palliation symptoms insight commonly asked questions methods comprehensive review current literature regarding incidence prevalence treatment cholangiocarcinoma conducted findings nursing literature regarding cholangiocarcinoma scarce studies focus nursing care symptom management nursing management patients biliary obstruction needed nutrition palliative care management patients cholangiocarcinoma key areas nursing management pubmed","probabilities":0.9799733,"Title":"Cholangiocarcinoma: Treatment, Outcomes, and Nutrition Overview for Oncology Nurses","Abstract":"BACKGROUND: Cholangiocarcinoma is a cancer that arises from the bile ducts inside or outside of the liver. Although it is a rare cancer, cholangiocarcinoma appears to be rising in incidence in the United States and worldwide. OBJECTIVES: The diagnosis of cholangiocarcinoma frequently presents with biliary emergencies from diagnosis through treatment. The lethality of this cancer stems, in part, from challenges with supportive care during treatment. This article provides an overview of intrahepatic and extrahepatic cholangiocarcinoma, including identification of risk factors, differences in treatment approaches, palliation of symptoms, and insight into commonly asked questions. METHODS: A comprehensive review of the current literature regarding incidence, prevalence, and treatment of cholangiocarcinoma was conducted. FINDINGS: Nursing literature regarding cholangiocarcinoma is scarce. Studies that focus on nursing care, symptom management, and nursing management of patients with biliary obstruction are needed. Nutrition and palliative care management of patients with cholangiocarcinoma are key areas of nursing management.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma: Treatment, Outcomes, and Nutrition Overview for Oncology Nurses BACKGROUND: Cholangiocarcinoma is a cancer that arises from the bile ducts inside or outside of the liver. Although it is a rare cancer, cholangiocarcinoma appears to be rising in incidence in the United States and worldwide. OBJECTIVES: The diagnosis of cholangiocarcinoma frequently presents with biliary emergencies from diagnosis through treatment. The lethality of this cancer stems, in part, from challenges with supportive care during treatment. This article provides an overview of intrahepatic and extrahepatic cholangiocarcinoma, including identification of risk factors, differences in treatment approaches, palliation of symptoms, and insight into commonly asked questions. METHODS: A comprehensive review of the current literature regarding incidence, prevalence, and treatment of cholangiocarcinoma was conducted. FINDINGS: Nursing literature regarding cholangiocarcinoma is scarce. Studies that focus on nursing care, symptom management, and nursing management of patients with biliary obstruction are needed. Nutrition and palliative care management of patients with cholangiocarcinoma are key areas of nursing management. PubMed","prediction_labels":"HUMAN"},{"cleaned":"asbestos hidden player behind cholangiocarcinoma increase findings case control analysis purposes conducted case control analysis explore association occupational exposure asbestos cholangiocarcinoma cc methods study based historical data 155 consecutive patients cc 69 intrahepatic cc icc 86 extrahepatic cc ecc referred sant orsola malpighi university hospital 2006 2010 cases individually matched calendar period birth sex region residence historical hospital population controls occupational exposure asbestos retrospectively assessed considering job titles obtained work histories separate conditional logistic regression models applied ecc icc estimates adjusted smoking status socioeconomic class results matched 149 controls median birth year 1947 males 56 41 cases icc median birth year 1946 males 56 212 controls median birth year 1945 males 48 59 cases ecc median birth year 1945 males 51 53 cases matched due residence birth year found increased risk icc workers exposed asbestos adjusted 4 81 95 ci 1 73 13 33 also observed suggestive evidence asbestos exposure might associated ecc adjusted 2 09 95 ci 0 83 5 27 sensitivity analysis restricted patients province bologna produced confirmatory figures conclusions findings suggest icc associated asbestos exposure chronic inflammatory pathway hypothesized exposure asbestos one determinants progressive rise incidence icc last 30 years pubmed","probabilities":0.9799733,"Title":"Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis","Abstract":"PURPOSES: We conducted a case-control analysis to explore the association between occupational exposure to asbestos and cholangiocarcinoma (CC). METHODS: The study was based on historical data from 155 consecutive patients with CC [69 intrahepatic CC (ICC) and 86 extrahepatic CC (ECC)] referred to Sant'Orsola-Malpighi University Hospital between 2006 and 2010. The cases were individually matched by calendar period of birth, sex, and region of residence to historical hospital and population controls. Occupational exposure to asbestos was retrospectively assessed considering job titles obtained from work histories. Separate conditional logistic regression models were applied for ECC and ICC. Estimates were adjusted for smoking status and socioeconomic class. RESULTS: We matched 149 controls (median birth year: 1947; males: 56 %) to 41 cases of ICC (median birth year: 1946; males: 56 %) and 212 controls (median birth year: 1945; males: 48 %) to 59 cases of ECC (median birth year: 1945; males 51 %); 53 cases were not matched due to residence or birth year. We found an increased risk of ICC in workers exposed to asbestos (adjusted OR 4.81, 95 % CI 1.73-13.33); we also observed suggestive evidence that asbestos exposure might be associated with ECC (adjusted OR 2.09, 95 % CI 0.83-5.27). Sensitivity analysis restricted to patients from the Province of Bologna produced confirmatory figures. CONCLUSIONS: Our findings suggest that ICC could be associated with asbestos exposure; a chronic inflammatory pathway is hypothesized. Exposure to asbestos could be one of the determinants of the progressive rise in the incidence of ICC during the last 30 years.","Source":"PubMed","category":"HUMAN","training_data":"Asbestos: a hidden player behind the cholangiocarcinoma increase? Findings from a case-control analysis PURPOSES: We conducted a case-control analysis to explore the association between occupational exposure to asbestos and cholangiocarcinoma (CC). METHODS: The study was based on historical data from 155 consecutive patients with CC [69 intrahepatic CC (ICC) and 86 extrahepatic CC (ECC)] referred to Sant'Orsola-Malpighi University Hospital between 2006 and 2010. The cases were individually matched by calendar period of birth, sex, and region of residence to historical hospital and population controls. Occupational exposure to asbestos was retrospectively assessed considering job titles obtained from work histories. Separate conditional logistic regression models were applied for ECC and ICC. Estimates were adjusted for smoking status and socioeconomic class. RESULTS: We matched 149 controls (median birth year: 1947; males: 56 %) to 41 cases of ICC (median birth year: 1946; males: 56 %) and 212 controls (median birth year: 1945; males: 48 %) to 59 cases of ECC (median birth year: 1945; males 51 %); 53 cases were not matched due to residence or birth year. We found an increased risk of ICC in workers exposed to asbestos (adjusted OR 4.81, 95 % CI 1.73-13.33); we also observed suggestive evidence that asbestos exposure might be associated with ECC (adjusted OR 2.09, 95 % CI 0.83-5.27). Sensitivity analysis restricted to patients from the Province of Bologna produced confirmatory figures. CONCLUSIONS: Our findings suggest that ICC could be associated with asbestos exposure; a chronic inflammatory pathway is hypothesized. Exposure to asbestos could be one of the determinants of the progressive rise in the incidence of ICC during the last 30 years. PubMed","prediction_labels":"HUMAN"},{"cleaned":"epidemiology risk factors biliary tract primary liver tumors primary liver biliary tract tumors encompass range benign malignant neoplasms consist histologically distinct types tumors arise influenced hepatocytes biliary epithelial cells mesenchymal cells improvements imaging allowed detection diagnosis neoplasms refined investigation histologic molecular genetic levels allowed neoplasms categorized treated epidemiology improved understanding geographic ethnic gender cultural differences link exposures cancer risk article focuses epidemiology major primary adult liver biliary tract tumors pubmed","probabilities":0.9799733,"Title":"Epidemiology and risk factors of biliary tract and primary liver tumors","Abstract":"Primary liver and biliary tract tumors encompass a range of benign and malignant neoplasms. They consist of histologically distinct types of tumors that arise from and are influenced by hepatocytes, biliary epithelial cells, and mesenchymal cells. Improvements in imaging have allowed the detection and diagnosis of these neoplasms to be refined. Investigation at the histologic, molecular, and genetic levels has allowed neoplasms to be categorized and treated. Epidemiology has improved understanding of geographic, ethnic, gender, and cultural differences that link exposures with cancer risk. This article focuses on the epidemiology of major primary adult liver and biliary tract tumors.","Source":"PubMed","category":"HUMAN","training_data":"Epidemiology and risk factors of biliary tract and primary liver tumors Primary liver and biliary tract tumors encompass a range of benign and malignant neoplasms. They consist of histologically distinct types of tumors that arise from and are influenced by hepatocytes, biliary epithelial cells, and mesenchymal cells. Improvements in imaging have allowed the detection and diagnosis of these neoplasms to be refined. Investigation at the histologic, molecular, and genetic levels has allowed neoplasms to be categorized and treated. Epidemiology has improved understanding of geographic, ethnic, gender, and cultural differences that link exposures with cancer risk. This article focuses on the epidemiology of major primary adult liver and biliary tract tumors. PubMed","prediction_labels":"HUMAN"},{"cleaned":"microrna 141 expression potential prognostic marker biliary tract cancers background aims recent years large number microribonucleic acids mirnas identified putative prognostic biomarkers solid cancers role controlling expression oncogenes tumor suppressor genes aim study verify utility mirna 141 prognostic biomarker biliary tract cancers methods june 2010 june 2012 common bile duct cancer tissue samples matched noncancerous tissues ampulla vater obtained patients biliary tract cancer undergoing endoscopic retrograde cholangiopancreatography using quantitative real time polymerase chain reaction assays measured mean relative expression levels mirna 141 groups tissues overexpression mirna 141 defined greater 2 fold increase expression levels determined 2 ct method results cohort 38 patients biliary tract cancers seven gallbladder 13 hilar 18 distal bile duct cancers 26 patients 68 4 male median age 69 5 52 85 years nineteen patients 50 undergone r0 resection procedures including three whipple operations seven pylorus preserving pancreaticoduodenectomies six bile duct resections three extended lobectomies among patients undergone r0 resection overexpression mirna 141 significantly associated shorter disease free survival greater risk angiolymphatic invasion among patients undergo r0 resection mirna 141 overexpression significantly associated reduced overall survival conclusions overexpression mirna 141 indicator poor prognosis patients biliary tract cancer suggesting mirna 141 may valuable prognostic biomarker disease pubmed","probabilities":0.88235295,"Title":"MicroRNA 141 Expression Is a Potential Prognostic Marker of Biliary Tract Cancers","Abstract":"BACKGROUND/AIMS: In recent years, a large number of microribonucleic acids (miRNAs) have been identified as putative prognostic biomarkers for solid cancers because of their role in controlling the expression of oncogenes and tumor suppressor genes. The aim of this study was to verify the utility of miRNA 141 as a prognostic biomarker of biliary tract cancers. METHODS: From June 2010 to June 2012, common bile duct cancer tissue samples and matched noncancerous tissues from the ampulla of Vater were obtained from patients with biliary tract cancer undergoing endoscopic retrograde cholangiopancreatography. Using quantitative real-time polymerase chain reaction assays, we measured the mean relative expression levels of miRNA 141 in both groups of tissues. Overexpression of miRNA 141 was defined as a greater than 2-fold increase in expression levels as determined by the 2(-ΔΔCt) method. RESULTS: In a cohort of 38 patients with biliary tract cancers (seven gallbladder, 13 hilar, and 18 distal bile duct cancers), 26 patients (68.4%) were male, and the median age was 69.5 (52 to 85) years. Nineteen patients (50%) had undergone R0 resection procedures, including three Whipple operations, seven pylorus-preserving pancreaticoduodenectomies, six bile duct resections, and three extended lobectomies. Among the patients who had undergone R0 resection, the overexpression of miRNA 141 was significantly associated with shorter disease-free survival and a greater risk of angiolymphatic invasion. Among the patients who did not undergo R0 resection, miRNA 141 overexpression was significantly associated with reduced overall survival. CONCLUSIONS: Overexpression of miRNA 141 is an indicator of a poor prognosis in patients with biliary tract cancer, suggesting that miRNA 141 may be a valuable prognostic biomarker of this disease.","Source":"PubMed","category":"HUMAN","training_data":"MicroRNA 141 Expression Is a Potential Prognostic Marker of Biliary Tract Cancers BACKGROUND/AIMS: In recent years, a large number of microribonucleic acids (miRNAs) have been identified as putative prognostic biomarkers for solid cancers because of their role in controlling the expression of oncogenes and tumor suppressor genes. The aim of this study was to verify the utility of miRNA 141 as a prognostic biomarker of biliary tract cancers. METHODS: From June 2010 to June 2012, common bile duct cancer tissue samples and matched noncancerous tissues from the ampulla of Vater were obtained from patients with biliary tract cancer undergoing endoscopic retrograde cholangiopancreatography. Using quantitative real-time polymerase chain reaction assays, we measured the mean relative expression levels of miRNA 141 in both groups of tissues. Overexpression of miRNA 141 was defined as a greater than 2-fold increase in expression levels as determined by the 2(-ΔΔCt) method. RESULTS: In a cohort of 38 patients with biliary tract cancers (seven gallbladder, 13 hilar, and 18 distal bile duct cancers), 26 patients (68.4%) were male, and the median age was 69.5 (52 to 85) years. Nineteen patients (50%) had undergone R0 resection procedures, including three Whipple operations, seven pylorus-preserving pancreaticoduodenectomies, six bile duct resections, and three extended lobectomies. Among the patients who had undergone R0 resection, the overexpression of miRNA 141 was significantly associated with shorter disease-free survival and a greater risk of angiolymphatic invasion. Among the patients who did not undergo R0 resection, miRNA 141 overexpression was significantly associated with reduced overall survival. CONCLUSIONS: Overexpression of miRNA 141 is an indicator of a poor prognosis in patients with biliary tract cancer, suggesting that miRNA 141 may be a valuable prognostic biomarker of this disease. PubMed","prediction_labels":"HUMAN"},{"cleaned":"laparoscopy versus open reoperation incidental gallbladder carcinoma laparoscopic cholecystectomy background reports assert risk laparoscopy might worsen prognosis incidental gallbladder carcinoma igbc laparoscopic cholecystectomy lc compared open reoperation purpose study evaluate whether surgical approach influences outcomes patients igbc lc methods retrospectively reviewed medical records 106 patients diagnosed igbc undergone lc benign gallbladder disease cholecystolithiasis hospital april 2010 february 2018 included patients incidentally diagnosed gbc routine pathology 45 patients 16 men 29 women age 45 76 years mean 62 6 years underwent laparoscopic surgery 61 patients 24 men 37 women age 51 82 years mean 62 6 years underwent open surgery evaluated outcomes group regarding tumor stage operative time time reoperation first operation blood loss volume number lymph nodes pathological specimens hospital stay complication survival rates results reoperation time first operation number lymph nodes pathological specimens operative time showed statistical significance laparoscopy open reoperation follow 3 year survival laparoscopy 48 89 open reoperation 42 62 showed statistical significance laparoscopy better 1 year survival 95 56 versus 86 89 laparoscopy versus open respectively significant ns 0 01 5 year survival 44 44 versus 29 51 laparoscopy versus open respectively ns 0 05 however comparing laparoscopy versus open surgery respectively blood loss volume 100 25 4 ml versus 200 45 6 ml ns 0 01 hospital stay 3 5 1 9 days versus 5 6 2 7 days ns 0 01 complication rates 6 7 versus 13 1 ns 0 01 lower indicating better recovery better patient experience conclusions laparoscopic radical reoperation igbc lc feasible effective safe procedure associated less bleeding low morbidity shorter hospital stay stn","probabilities":0.9799733,"Title":"Laparoscopy Versus Open Reoperation For Incidental Gallbladder Carcinoma After Laparoscopic Cholecystectomy","Abstract":"Background: Some reports assert that there is a risk that laparoscopy might worsen the prognosis of incidental gallbladder carcinoma (IGBC) after laparoscopic cholecystectomy (LC) compared with open reoperation. The purpose of this study was to evaluate whether the surgical approach influences outcomes in patients with IGBC after LC. Methods: We retrospectively reviewed the medical records of 106 patients diagnosed with IGBC who had undergone LC for benign gallbladder disease such as cholecystolithiasis at our hospital between April 2010 and February 2018. We included patients with incidentally diagnosed GBC after routine pathology: 45 patients (16 men and 29 women; age: 45-76 years [mean: 62.6 years]) who underwent laparoscopic surgery and 61 patients (24 men and 37 women; age: 51-82 years [mean: 62.6 years]) who underwent open surgery. We evaluated outcomes in each group regarding tumor stage and operative time, time of reoperation after first operation, blood loss volume, number of lymph nodes in pathological specimens, hospital stay, and complication and survival rates. Results: Reoperation time after first operation, number of lymph nodes in pathological specimens, and operative time showed no statistical significance between laparoscopy and open reoperation. During follow-up, 3-year survival between laparoscopy (48.89%) and open reoperation (42.62%) showed no statistical significance, but laparoscopy had better 1-year survival (95.56% versus 86.89%, laparoscopy versus open, respectively; not significant [NS] <0.01) and 5-year survival (44.44% versus 29.51%, laparoscopy versus open, respectively; NS <0.05). However, comparing laparoscopy versus open surgery, respectively, blood -loss volume (100 ± 25.4 mL versus 200 ± 45.6 mL; NS <0.01), hospital stay (3.5 ± 1.9 days versus 5.6 ± 2.7 days, NS <0.01), and complication rates (6.7% versus 13.1%; NS <0.01) were lower, indicating better recovery and better patient experience. Conclusions: Laparoscopic radical reoperation for IGBC after LC is a feasible, effective, and safe procedure and is associated with less bleeding, low morbidity, and shorter hospital stay.","Source":"STN","category":"HUMAN","training_data":"Laparoscopy Versus Open Reoperation For Incidental Gallbladder Carcinoma After Laparoscopic Cholecystectomy Background: Some reports assert that there is a risk that laparoscopy might worsen the prognosis of incidental gallbladder carcinoma (IGBC) after laparoscopic cholecystectomy (LC) compared with open reoperation. The purpose of this study was to evaluate whether the surgical approach influences outcomes in patients with IGBC after LC. Methods: We retrospectively reviewed the medical records of 106 patients diagnosed with IGBC who had undergone LC for benign gallbladder disease such as cholecystolithiasis at our hospital between April 2010 and February 2018. We included patients with incidentally diagnosed GBC after routine pathology: 45 patients (16 men and 29 women; age: 45-76 years [mean: 62.6 years]) who underwent laparoscopic surgery and 61 patients (24 men and 37 women; age: 51-82 years [mean: 62.6 years]) who underwent open surgery. We evaluated outcomes in each group regarding tumor stage and operative time, time of reoperation after first operation, blood loss volume, number of lymph nodes in pathological specimens, hospital stay, and complication and survival rates. Results: Reoperation time after first operation, number of lymph nodes in pathological specimens, and operative time showed no statistical significance between laparoscopy and open reoperation. During follow-up, 3-year survival between laparoscopy (48.89%) and open reoperation (42.62%) showed no statistical significance, but laparoscopy had better 1-year survival (95.56% versus 86.89%, laparoscopy versus open, respectively; not significant [NS] <0.01) and 5-year survival (44.44% versus 29.51%, laparoscopy versus open, respectively; NS <0.05). However, comparing laparoscopy versus open surgery, respectively, blood -loss volume (100 ± 25.4 mL versus 200 ± 45.6 mL; NS <0.01), hospital stay (3.5 ± 1.9 days versus 5.6 ± 2.7 days, NS <0.01), and complication rates (6.7% versus 13.1%; NS <0.01) were lower, indicating better recovery and better patient experience. Conclusions: Laparoscopic radical reoperation for IGBC after LC is a feasible, effective, and safe procedure and is associated with less bleeding, low morbidity, and shorter hospital stay. STN","prediction_labels":"HUMAN"},{"cleaned":"impact prior hepatectomy safety efficacy radioembolization yttrium 90 microspheres patients unresectable liver tumors objectives yttrium 90 y radioembolization increasingly used minimally invasive therapy unresectable liver tumors however previous hepatectomy must considered avoid excessive hepatic insult retrospective analysis undertaken investigate viability performing radioembolization remnant liver methods retrospective analysis performed data collected december 2005 august 2011 identify effect prior hepatectomy radioembolization outcomes survival complications reviewed 3 months radioembolization results 427 patients eligible analysis 89 underwent previous hepatectomy immediate adverse events included abdominal pain 7 9 hepatectomy patients vs 18 0 non hepatectomy patients p 0 02 nausea 4 5 vs 8 0 p 0 05 emesis 0 0 vs 0 9 p 0 05 prevalence intermediate complications 1 month radioembolization low late complications included radiation induced liver disease 3 4 vs 1 5 p 0 05 ulceration 2 2 vs 2 7 p 0 05 gallbladder biliary tree related outcomes 2 2 vs 1 8 p 0 05 imaging analysis demonstrated significant relationship prior hepatectomy patients partial response radioembolization well progressive disease median overall survival radioembolization hepatectomy patients 7 8 months versus 5 8 months non hepatectomy patients p 0 108 conclusions results indicate radioembolization safe performed remnant liver although imaging analysis demonstrated varying responses radioembolization comparing hepatectomy patients non hepatectomy patients overall survival shown similar 2 groups pubmed","probabilities":0.9799733,"Title":"Impact of prior hepatectomy on the safety and efficacy of radioembolization with yttrium-90 microspheres for patients with unresectable liver tumors","Abstract":"OBJECTIVES: Yttrium-90 (Y) radioembolization is increasingly used as a minimally invasive therapy for unresectable liver tumors; however, previous hepatectomy must be considered to avoid excessive hepatic insult. A retrospective analysis was undertaken to investigate the viability of performing radioembolization on a remnant liver. METHODS: A retrospective analysis was performed on data collected from December 2005 to August 2011 to identify the effect of prior hepatectomy on radioembolization outcomes. Survival and complications were reviewed for up to 3 months after radioembolization. RESULTS: Of 427 patients eligible for analysis, 89 underwent previous hepatectomy. Immediate adverse events included abdominal pain (7.9% of hepatectomy patients vs. 18.0% of non-hepatectomy patients; P = 0.02), nausea (4.5% vs. 8.0%; P > 0.05), and emesis (0.0% vs. 0.9%; P > 0.05). The prevalence of intermediate complications 1 month after radioembolization was low. Late complications included radiation-induced liver disease (3.4% vs. 1.5%; P > 0.05), ulceration (2.2% vs. 2.7%; P > 0.05), and gallbladder and biliary tree-related outcomes (2.2% vs. 1.8%; P > 0.05). Imaging analysis demonstrated a significant relationship between prior hepatectomy patients and a partial response to radioembolization, as well as progressive disease. The median overall survival after radioembolization for hepatectomy patients was 7.8 months, versus 5.8 months for non-hepatectomy patients (P = 0.108). CONCLUSIONS: Our results indicate that radioembolization is safe to be performed on a remnant liver. Although imaging analysis demonstrated varying responses to radioembolization when comparing hepatectomy patients to non-hepatectomy patients, overall survival was shown to be similar between the 2 groups.","Source":"PubMed","category":"HUMAN","training_data":"Impact of prior hepatectomy on the safety and efficacy of radioembolization with yttrium-90 microspheres for patients with unresectable liver tumors OBJECTIVES: Yttrium-90 (Y) radioembolization is increasingly used as a minimally invasive therapy for unresectable liver tumors; however, previous hepatectomy must be considered to avoid excessive hepatic insult. A retrospective analysis was undertaken to investigate the viability of performing radioembolization on a remnant liver. METHODS: A retrospective analysis was performed on data collected from December 2005 to August 2011 to identify the effect of prior hepatectomy on radioembolization outcomes. Survival and complications were reviewed for up to 3 months after radioembolization. RESULTS: Of 427 patients eligible for analysis, 89 underwent previous hepatectomy. Immediate adverse events included abdominal pain (7.9% of hepatectomy patients vs. 18.0% of non-hepatectomy patients; P = 0.02), nausea (4.5% vs. 8.0%; P > 0.05), and emesis (0.0% vs. 0.9%; P > 0.05). The prevalence of intermediate complications 1 month after radioembolization was low. Late complications included radiation-induced liver disease (3.4% vs. 1.5%; P > 0.05), ulceration (2.2% vs. 2.7%; P > 0.05), and gallbladder and biliary tree-related outcomes (2.2% vs. 1.8%; P > 0.05). Imaging analysis demonstrated a significant relationship between prior hepatectomy patients and a partial response to radioembolization, as well as progressive disease. The median overall survival after radioembolization for hepatectomy patients was 7.8 months, versus 5.8 months for non-hepatectomy patients (P = 0.108). CONCLUSIONS: Our results indicate that radioembolization is safe to be performed on a remnant liver. Although imaging analysis demonstrated varying responses to radioembolization when comparing hepatectomy patients to non-hepatectomy patients, overall survival was shown to be similar between the 2 groups. PubMed","prediction_labels":"HUMAN"},{"cleaned":"ampullary cancer separate clinical entity aims ampullary cancer relatively uncommon tumour better prognosis pancreatic cancer purpose study review recent literature ampullary adenocarcinoma focusing histological types prognostic factors methods results using pubmed carried comprehensive search literature extended april 2013 retrieve additional publications ampullary cancer comprises two main histological subtypes pancreatobiliary type intestinal type subtypes different pathogenetic clinical characteristics clinical histological parameters well immunohistochemical markers identified significant prognostic factors ampullary cancer moreover several immunohistochemical markers studied prognostic factors means differentiating ampullary peri ampullary tumours identifying exact histological subtype conclusions considerable differences frequencies two subtypes ampullary tumours reported literature reinforce necessity define molecular markers distinguish significance histological subtype prognostic factor evaluated cautiously future research pathogenesis ampullary cancer possibly suggest stop treating type cancer separate entity pubmed","probabilities":0.9799733,"Title":"Ampullary cancer--a separate clinical entity?","Abstract":"AIMS: Ampullary cancer is a relatively uncommon tumour, with a better prognosis than pancreatic cancer. The purpose of this study was to review the recent literature on ampullary adenocarcinoma, focusing on histological types and prognostic factors. METHODS AND RESULTS: Using PubMed, we carried out a comprehensive search of the literature, which was extended to April 2013 to retrieve all additional publications. Ampullary cancer comprises two main histological subtypes, the pancreatobiliary type and the intestinal type. These subtypes have different pathogenetic and clinical characteristics. Clinical and histological parameters as well as immunohistochemical markers have been identified as significant prognostic factors in ampullary cancer. Moreover, several immunohistochemical markers have been studied, not only as prognostic factors but as a means of differentiating ampullary from other peri-ampullary tumours, and of identifying the exact histological subtype. CONCLUSIONS: The considerable differences in the frequencies of the two subtypes of ampullary tumours reported in literature reinforce the necessity to define molecular markers to distinguish them. Until then, the significance of the histological subtype as a prognostic factor should be evaluated cautiously. Future research on the pathogenesis of ampullary cancer will possibly suggest that we should stop treating this type of cancer as a separate entity.","Source":"PubMed","category":"HUMAN","training_data":"Ampullary cancer--a separate clinical entity? AIMS: Ampullary cancer is a relatively uncommon tumour, with a better prognosis than pancreatic cancer. The purpose of this study was to review the recent literature on ampullary adenocarcinoma, focusing on histological types and prognostic factors. METHODS AND RESULTS: Using PubMed, we carried out a comprehensive search of the literature, which was extended to April 2013 to retrieve all additional publications. Ampullary cancer comprises two main histological subtypes, the pancreatobiliary type and the intestinal type. These subtypes have different pathogenetic and clinical characteristics. Clinical and histological parameters as well as immunohistochemical markers have been identified as significant prognostic factors in ampullary cancer. Moreover, several immunohistochemical markers have been studied, not only as prognostic factors but as a means of differentiating ampullary from other peri-ampullary tumours, and of identifying the exact histological subtype. CONCLUSIONS: The considerable differences in the frequencies of the two subtypes of ampullary tumours reported in literature reinforce the necessity to define molecular markers to distinguish them. Until then, the significance of the histological subtype as a prognostic factor should be evaluated cautiously. Future research on the pathogenesis of ampullary cancer will possibly suggest that we should stop treating this type of cancer as a separate entity. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical outcomes multicentric adenocarcinomas biliary tract objective comparison single biliary cancers distinct features biliary multicentric adenocarcinomas yet clear methods july 1992 july 2009 393 patients underwent surgery cancers biliary tract national cancer center hospital east kashiwa japan clinicopathological characteristics surgical outcomes multicentric biliary adenocarcinoma compared single cancers results period 10 cases 2 5 multicentric cancer 6 synchronous 4 metachronous cancers found among 393 cases biliary cancer pathologically compared single cancers multicentric adenocarcinomas likely early cancers papillary carcinomas superficial epithelial tumor spread extensive dysplastic epithelium less likely lymph node metastases p 0 01 proportion multicentric cancers among early papillary cancers high 9 24 37 5 clinically recurrences detected lymph nodes peritoneum distant organs one recurrence remnant bile duct one patient died cancer progression overall survival patients multicentric adenocarcinomas statistically single cancers median survival 69 vs 30 months p 0 47 conclusions multicentric adenocarcinomas biliary tract distinct features compared single cancers pubmed","probabilities":0.9799733,"Title":"Surgical outcomes of multicentric adenocarcinomas of the biliary tract","Abstract":"OBJECTIVE: In comparison to single biliary cancers, distinct features of biliary multicentric adenocarcinomas are not yet clear. METHODS: From July 1992 to July 2009, 393 patients underwent surgery for cancers of the biliary tract at the National Cancer Center Hospital East, Kashiwa, Japan. Clinicopathological characteristics and surgical outcomes of multicentric biliary adenocarcinoma were compared with those of single cancers. RESULTS: During the period, 10 cases (2.5%) with multicentric cancer (6 synchronous and 4 metachronous cancers) were found among 393 cases of biliary cancer. Pathologically, compared with single cancers, multicentric adenocarcinomas were more likely to be early cancers and to be papillary carcinomas with both superficial epithelial tumor spread and extensive dysplastic epithelium, but were less likely to have lymph node metastases (P < 0.01). The proportion of multicentric cancers among early papillary cancers was high (9/24, 37.5%). Clinically, no recurrences were detected in lymph nodes, peritoneum or distant organs, but one recurrence in the remnant bile duct. Only one patient died from cancer progression. The overall survival of patients with multicentric adenocarcinomas was statistically the same as that of single cancers (median survival: 69 vs. 30 months, P = 0.47). CONCLUSIONS: Multicentric adenocarcinomas of the biliary tract have distinct features compared with single cancers.","Source":"PubMed","category":"HUMAN","training_data":"Surgical outcomes of multicentric adenocarcinomas of the biliary tract OBJECTIVE: In comparison to single biliary cancers, distinct features of biliary multicentric adenocarcinomas are not yet clear. METHODS: From July 1992 to July 2009, 393 patients underwent surgery for cancers of the biliary tract at the National Cancer Center Hospital East, Kashiwa, Japan. Clinicopathological characteristics and surgical outcomes of multicentric biliary adenocarcinoma were compared with those of single cancers. RESULTS: During the period, 10 cases (2.5%) with multicentric cancer (6 synchronous and 4 metachronous cancers) were found among 393 cases of biliary cancer. Pathologically, compared with single cancers, multicentric adenocarcinomas were more likely to be early cancers and to be papillary carcinomas with both superficial epithelial tumor spread and extensive dysplastic epithelium, but were less likely to have lymph node metastases (P < 0.01). The proportion of multicentric cancers among early papillary cancers was high (9/24, 37.5%). Clinically, no recurrences were detected in lymph nodes, peritoneum or distant organs, but one recurrence in the remnant bile duct. Only one patient died from cancer progression. The overall survival of patients with multicentric adenocarcinomas was statistically the same as that of single cancers (median survival: 69 vs. 30 months, P = 0.47). CONCLUSIONS: Multicentric adenocarcinomas of the biliary tract have distinct features compared with single cancers. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic value portal vein hepatic artery involvement patients perihilar cholangiocarcinoma background although several classifications perihilar cholangiocarcinoma phc include vascular involvement prognostic value investigated aim assess prognostic value unilateral main bilateral involvement portal vein pv hepatic artery ha imaging patients phc methods patients phc 2002 2014 included regardless stage management vascular involvement defined apparent tumor contact least 180 pv ha imaging kaplan meier method log rank test used compare overall survival os groups cox regression used multivariable analysis results total 674 patients included median os 12 2 95 ci 10 6 13 7 months patients unilateral pv involvement median os 13 3 11 0 15 7 months compared 14 7 11 7 17 6 patients without pv involvement p 0 12 patients main bilateral pv involvement inferior median os 8 0 5 4 10 7 p 0 001 months median os patients unilateral ha involvement 10 6 9 3 12 0 months compared 16 9 13 2 20 5 patients without ha involvement p 0 001 patients main bilateral ha involvement inferior median os 6 9 3 3 10 5 p 0 001 independent poor prognostic factors included unilateral main bilateral ha involvement pv involvement conclusion unilateral main ha involvement independent poor prognostic factors os patients presenting phc whereas pv involvement pubmed","probabilities":0.9799733,"Title":"The prognostic value of portal vein and hepatic artery involvement in patients with perihilar cholangiocarcinoma","Abstract":"BACKGROUND: Although several classifications of perihilar cholangiocarcinoma (PHC) include vascular involvement, its prognostic value has not been investigated. Our aim was to assess the prognostic value of unilateral and main/bilateral involvement of the portal vein (PV) and hepatic artery (HA) on imaging in patients with PHC. METHODS: All patients with PHC between 2002 and 2014 were included regardless of stage or management. Vascular involvement was defined as apparent tumor contact of at least 180° to the PV or HA on imaging. Kaplan-Meier method with log-rank test was used to compare overall survival (OS) between groups. Cox regression was used for multivariable analysis. RESULTS: In total, 674 patients were included with a median OS of 12.2 (95% CI 10.6-13.7) months. Patients with unilateral PV involvement had a median OS of 13.3 (11.0-15.7) months, compared with 14.7 (11.7-17.6) in patients without PV involvement (p = 0.12). Patients with main/bilateral PV involvement had an inferior median OS of 8.0 (5.4-10.7, p < 0.001) months. Median OS for patients with unilateral HA involvement was 10.6 (9.3-12.0) months compared with 16.9 (13.2-20.5) in patients without HA involvement (p < 0.001). Patients with main/bilateral HA involvement had an inferior median OS of 6.9 (3.3-10.5, p < 0.001). Independent poor prognostic factors included unilateral and main/bilateral HA involvement, but not PV involvement. CONCLUSION: Both unilateral and main HA involvement are independent poor prognostic factors for OS in patients presenting with PHC, whereas PV involvement is not.","Source":"PubMed","category":"HUMAN","training_data":"The prognostic value of portal vein and hepatic artery involvement in patients with perihilar cholangiocarcinoma BACKGROUND: Although several classifications of perihilar cholangiocarcinoma (PHC) include vascular involvement, its prognostic value has not been investigated. Our aim was to assess the prognostic value of unilateral and main/bilateral involvement of the portal vein (PV) and hepatic artery (HA) on imaging in patients with PHC. METHODS: All patients with PHC between 2002 and 2014 were included regardless of stage or management. Vascular involvement was defined as apparent tumor contact of at least 180° to the PV or HA on imaging. Kaplan-Meier method with log-rank test was used to compare overall survival (OS) between groups. Cox regression was used for multivariable analysis. RESULTS: In total, 674 patients were included with a median OS of 12.2 (95% CI 10.6-13.7) months. Patients with unilateral PV involvement had a median OS of 13.3 (11.0-15.7) months, compared with 14.7 (11.7-17.6) in patients without PV involvement (p = 0.12). Patients with main/bilateral PV involvement had an inferior median OS of 8.0 (5.4-10.7, p < 0.001) months. Median OS for patients with unilateral HA involvement was 10.6 (9.3-12.0) months compared with 16.9 (13.2-20.5) in patients without HA involvement (p < 0.001). Patients with main/bilateral HA involvement had an inferior median OS of 6.9 (3.3-10.5, p < 0.001). Independent poor prognostic factors included unilateral and main/bilateral HA involvement, but not PV involvement. CONCLUSION: Both unilateral and main HA involvement are independent poor prognostic factors for OS in patients presenting with PHC, whereas PV involvement is not. PubMed","prediction_labels":"HUMAN"},{"cleaned":"therapeutic rationale target highly expressed aurora kinase conferring poor prognosis cholangiocarcinoma background cholangiocarcinoma highly lethal neoplasm currently available chemotherapeutic agents suboptimal numerous studies show alterations expression genes related mitotic spindle mitotic checkpoint involved chromosomal instability tumor progression various malignancies study aimed evaluate genes cholangiocarcinoma patients material methods different public datasets analyzed examine expression 76 selected mitotic spindle checkpoint genes including aurora kinase aurka cholangiocarcinoma afterwards cell number counting cck 8 assay caspase 3 7 assay used explore antitumor effect aurka inhibitor alisertib vitro addition xenograft model used evaluate antitumor effect alisertib vivo furthermore sirna mediated silencing aurka used verify function aurka cholangiocarcinoma results components mitotic spindle checkpoint including aurka broadly dysregulated human cholangiocarcinoma high aurka mrna expression associated poor survival cholangiocarcinoma patients within different datasets aurka specific inhibitor alisertib inhibited cell growth induced cell cycle arrest g2 m phase promoted apoptosis cholangiocarcinoma cell lines additionally alisertib also inhibited tumor growth cholangiocarcinoma xenograft mouse model furthermore aurka knockdown sirna recapitulated antitumor effect alisertib aurka expression also highly correlated interaction proteins polo like kinase 1 plk1 targeting protein xenopus kinesin like protein2 tpx2 different cholangiocarcinoma datasets conclusions highly expressed aurka confers poor outcomes cholangiocarcinoma may represent rational therapeutic target stn","probabilities":0.9467213,"Title":"Therapeutic Rationale To Target Highly Expressed Aurora Kinase A Conferring Poor Prognosis In Cholangiocarcinoma","Abstract":"Background: Cholangiocarcinoma is a highly lethal neoplasm for which the currently available chemotherapeutic agents are suboptimal. Numerous studies show that alterations in expression of genes related to mitotic spindle and mitotic checkpoint are involved in chromosomal instability and tumor progression in various malignancies. This study aimed to evaluate these genes in cholangiocarcinoma patients. Material and methods: Different public datasets were analyzed to examine the expression of 76 selected mitotic spindle checkpoint genes including Aurora Kinase A (AURKA) in cholangiocarcinoma. Afterwards, cell number counting, CCK-8 assay, and Caspase 3/7 assay were used to explore the antitumor effect of AURKA inhibitor Alisertib in vitro. In addition, xenograft model was used to evaluate the antitumor effect of Alisertib in vivo. Furthermore, siRNA mediated silencing of AURKA was used to verify the function of AURKA in cholangiocarcinoma. Results: Components of the mitotic spindle checkpoint, including AURKA, were broadly dysregulated in human cholangiocarcinoma. High AURKA mRNA expression was associated with poor survival in cholangiocarcinoma patients within different datasets. AURKA specific inhibitor Alisertib, inhibited cell growth, induced cell cycle arrest in G2/M phase, and promoted apoptosis in cholangiocarcinoma cell lines. Additionally, Alisertib also inhibited tumor growth in a cholangiocarcinoma xenograft mouse model. Furthermore, AURKA knockdown by siRNA recapitulated the antitumor effect of Alisertib. AURKA expression was also highly correlated with its interaction proteins Polo-like kinase 1(PLK1) and Targeting protein for xenopus kinesin-like protein2 (TPX2) in different cholangiocarcinoma datasets. Conclusions: Highly expressed AURKA confers poor outcomes in cholangiocarcinoma and may represent a rational therapeutic target.","Source":"STN","category":"ANIMAL","training_data":"Therapeutic Rationale To Target Highly Expressed Aurora Kinase A Conferring Poor Prognosis In Cholangiocarcinoma Background: Cholangiocarcinoma is a highly lethal neoplasm for which the currently available chemotherapeutic agents are suboptimal. Numerous studies show that alterations in expression of genes related to mitotic spindle and mitotic checkpoint are involved in chromosomal instability and tumor progression in various malignancies. This study aimed to evaluate these genes in cholangiocarcinoma patients. Material and methods: Different public datasets were analyzed to examine the expression of 76 selected mitotic spindle checkpoint genes including Aurora Kinase A (AURKA) in cholangiocarcinoma. Afterwards, cell number counting, CCK-8 assay, and Caspase 3/7 assay were used to explore the antitumor effect of AURKA inhibitor Alisertib in vitro. In addition, xenograft model was used to evaluate the antitumor effect of Alisertib in vivo. Furthermore, siRNA mediated silencing of AURKA was used to verify the function of AURKA in cholangiocarcinoma. Results: Components of the mitotic spindle checkpoint, including AURKA, were broadly dysregulated in human cholangiocarcinoma. High AURKA mRNA expression was associated with poor survival in cholangiocarcinoma patients within different datasets. AURKA specific inhibitor Alisertib, inhibited cell growth, induced cell cycle arrest in G2/M phase, and promoted apoptosis in cholangiocarcinoma cell lines. Additionally, Alisertib also inhibited tumor growth in a cholangiocarcinoma xenograft mouse model. Furthermore, AURKA knockdown by siRNA recapitulated the antitumor effect of Alisertib. AURKA expression was also highly correlated with its interaction proteins Polo-like kinase 1(PLK1) and Targeting protein for xenopus kinesin-like protein2 (TPX2) in different cholangiocarcinoma datasets. Conclusions: Highly expressed AURKA confers poor outcomes in cholangiocarcinoma and may represent a rational therapeutic target. STN","prediction_labels":"ANIMAL"},{"cleaned":"interleukin 33 overexpression reflects less aggressive tumour features large duct type cholangiocarcinomas aims aim present study elucidate clinicopathological significance interleukin il 6 il 33 expression intrahepatic cholangiocarcinomas iccas perihilar cholangiocarcinomas pccas methods results il 6 il 33 mrna expression levels examined iccas n 55 pccas n 32 use quantitative real time polymerase chain reaction highly sensitive situ hybridisation protocol rnascope expression levels correlated clinicopathological features according recently proposed classification scheme iccas separated small duct n 33 large duct n 22 types il 6 il 33 expression levels higher large duct iccas pccas small duct iccas positive correlation expression levels cytokines double situ hybridisation immunostaining showed il 6 mrna expressed actin positive myo fibroblasts whereas il 33 mrna mainly produced cd31 positive endothelial cells average expression level cut point cases classified il 6 high il 6 low il 33 high il 33 low combined cohort large duct iccas pccas il 6 high il 6 low cholangiocarcinomas shared many features whereas il 33 high cases less aggressive characteristics il 33 low cases shown lower tumour marker concentrations smaller tumour sizes less common vascular invasion lower pt stages higher lymphocyte monocyte ratios blood kras mutations slightly less common il 33 high cases il 33 low cases 9 versus 29 p 0 061 strong expression il 33 tissue appeared independent favourable prognostic factor conclusions il 33 high cholangiocarcinomas may represent unique less aggressive carcinogenetic process large bile ducts pubmed","probabilities":0.7966102,"Title":"Interleukin-33 overexpression reflects less aggressive tumour features in large-duct type cholangiocarcinomas","Abstract":"AIMS: The aim of the present study was to elucidate the clinicopathological significance of interleukin (IL)-6 and IL-33 expression in intrahepatic cholangiocarcinomas (iCCAs) and perihilar cholangiocarcinomas (pCCAs). METHODS AND RESULTS: IL-6 and IL-33 mRNA expression levels were examined in iCCAs (n = 55) and pCCAs (n = 32) by the use of quantitative real-time polymerase chain reaction and a highly sensitive in-situ hybridisation protocol (RNAscope), and expression levels were correlated with clinicopathological features. According to a recently proposed classification scheme, iCCAs were separated into small-duct (n = 33) and large-duct (n = 22) types. IL-6 and IL-33 expression levels were higher in large-duct iCCAs and pCCAs than in small-duct iCCAs, and there was a positive correlation between the expression levels of these cytokines. Double in-situ hybridisation/immunostaining showed that IL-6 mRNA was expressed in actin-positive (myo)fibroblasts, whereas IL-33 mRNA was mainly produced by CD31-positive endothelial cells. With the average expression level as a cut-off point, cases were classified as IL-6(high) and IL-6(low) or IL-33(high) and IL-33(low) . In the combined cohort of large-duct iCCAs and pCCAs, IL-6(high) and IL-6(low) cholangiocarcinomas shared many features, whereas IL-33(high) cases had less aggressive characteristics than IL-33(low) cases, as shown by lower tumour marker concentrations, smaller tumour sizes, less common vascular invasion, lower pT stages, and higher lymphocyte/monocyte ratios in blood. KRAS mutations were slightly less common in IL-33(high) cases than in IL-33(low) cases (9% versus 29%; P = 0.061). The strong expression of IL-33 in tissue appeared to be an independent favourable prognostic factor. CONCLUSIONS: IL-33(high) cholangiocarcinomas may represent a unique, less aggressive carcinogenetic process of the large bile ducts.","Source":"PubMed","category":"HUMAN","training_data":"Interleukin-33 overexpression reflects less aggressive tumour features in large-duct type cholangiocarcinomas AIMS: The aim of the present study was to elucidate the clinicopathological significance of interleukin (IL)-6 and IL-33 expression in intrahepatic cholangiocarcinomas (iCCAs) and perihilar cholangiocarcinomas (pCCAs). METHODS AND RESULTS: IL-6 and IL-33 mRNA expression levels were examined in iCCAs (n = 55) and pCCAs (n = 32) by the use of quantitative real-time polymerase chain reaction and a highly sensitive in-situ hybridisation protocol (RNAscope), and expression levels were correlated with clinicopathological features. According to a recently proposed classification scheme, iCCAs were separated into small-duct (n = 33) and large-duct (n = 22) types. IL-6 and IL-33 expression levels were higher in large-duct iCCAs and pCCAs than in small-duct iCCAs, and there was a positive correlation between the expression levels of these cytokines. Double in-situ hybridisation/immunostaining showed that IL-6 mRNA was expressed in actin-positive (myo)fibroblasts, whereas IL-33 mRNA was mainly produced by CD31-positive endothelial cells. With the average expression level as a cut-off point, cases were classified as IL-6(high) and IL-6(low) or IL-33(high) and IL-33(low) . In the combined cohort of large-duct iCCAs and pCCAs, IL-6(high) and IL-6(low) cholangiocarcinomas shared many features, whereas IL-33(high) cases had less aggressive characteristics than IL-33(low) cases, as shown by lower tumour marker concentrations, smaller tumour sizes, less common vascular invasion, lower pT stages, and higher lymphocyte/monocyte ratios in blood. KRAS mutations were slightly less common in IL-33(high) cases than in IL-33(low) cases (9% versus 29%; P = 0.061). The strong expression of IL-33 in tissue appeared to be an independent favourable prognostic factor. CONCLUSIONS: IL-33(high) cholangiocarcinomas may represent a unique, less aggressive carcinogenetic process of the large bile ducts. PubMed","prediction_labels":"HUMAN"},{"cleaned":"novel serum biomarkers differentiate cholangiocarcinoma benign biliary tract diseases using proteomic approach background aim cholangiocarcinoma cca frequent biliary malignancy poses high mortality rate due lack early detection hence cca cases present advanced late stages local distant metastasis time diagnosis currently available tumor markers including ca19 9 cea inefficient limited usage due low sensitivity specificity attempt identify serum tumor markers cca effectively distinguish cca benign biliary tract diseases bbtds methods serum samples 19 cca patients 17 bbtds separated sds page followed lc ms ms subjected statistical analysis cross validation identify proteins whose abundance significantly elevated suppressed cca samples compared bbtds results addition identifying several proteins previously known differentially expressed cca bbtds also discovered number molecules previously associated cca included fam19a5 maged4b kiaa0321 rbak upf3b conclusions novel serum biomarkers distinguish cca bbtds identified using proteomic approach validation proteins potential provide biomarker differentiating cca bbtds pubmed","probabilities":0.9799733,"Title":"Novel Serum Biomarkers to Differentiate Cholangiocarcinoma from Benign Biliary Tract Diseases Using a Proteomic Approach","Abstract":"BACKGROUND AND AIM: Cholangiocarcinoma (CCA) is the most frequent biliary malignancy, which poses high mortality rate due to lack of early detection. Hence, most CCA cases are present at the advanced to late stages with local or distant metastasis at the time of diagnosis. Currently available tumor markers including CA19-9 and CEA are inefficient and of limited usage due to low sensitivity and specificity. Here, we attempt to identify serum tumor markers for CCA that can effectively distinguish CCA from benign biliary tract diseases (BBTDs). METHODS: Serum samples from 19 CCA patients and 17 BBTDs were separated by SDS-PAGE followed with LC-MS/MS and were subjected to statistical analysis and cross-validation to identify proteins whose abundance was significantly elevated or suppressed in CCA samples compared to BBTDs. RESULTS: In addition to identifying several proteins previously known to be differentially expressed in CCA and BBTDs, we also discovered a number of molecules that were previously not associated with CCA. These included FAM19A5, MAGED4B, KIAA0321, RBAK, and UPF3B. CONCLUSIONS: Novel serum biomarkers to distinguish CCA from BBTDs were identified using a proteomic approach. Further validation of these proteins has the potential to provide a biomarker for differentiating CCA from BBTDs.","Source":"PubMed","category":"HUMAN","training_data":"Novel Serum Biomarkers to Differentiate Cholangiocarcinoma from Benign Biliary Tract Diseases Using a Proteomic Approach BACKGROUND AND AIM: Cholangiocarcinoma (CCA) is the most frequent biliary malignancy, which poses high mortality rate due to lack of early detection. Hence, most CCA cases are present at the advanced to late stages with local or distant metastasis at the time of diagnosis. Currently available tumor markers including CA19-9 and CEA are inefficient and of limited usage due to low sensitivity and specificity. Here, we attempt to identify serum tumor markers for CCA that can effectively distinguish CCA from benign biliary tract diseases (BBTDs). METHODS: Serum samples from 19 CCA patients and 17 BBTDs were separated by SDS-PAGE followed with LC-MS/MS and were subjected to statistical analysis and cross-validation to identify proteins whose abundance was significantly elevated or suppressed in CCA samples compared to BBTDs. RESULTS: In addition to identifying several proteins previously known to be differentially expressed in CCA and BBTDs, we also discovered a number of molecules that were previously not associated with CCA. These included FAM19A5, MAGED4B, KIAA0321, RBAK, and UPF3B. CONCLUSIONS: Novel serum biomarkers to distinguish CCA from BBTDs were identified using a proteomic approach. Further validation of these proteins has the potential to provide a biomarker for differentiating CCA from BBTDs. PubMed","prediction_labels":"HUMAN"},{"cleaned":"obesity tumour development triggering factor introduction overweight obesity epidemic represents rapidly growing threat health populations increasing number countries nearly one third world population excess adipose tissue nowadays obesity occurrence common replacing traditional problems undernutrition infectious diseases significant causes ill health current trend continues almost half world adult population overweight obese 2030 objective aim study show connection recent trends body mass index globally changing cancer profile state knowledge range clinical epidemiological studies shown relationship excess body fat frequently occurring malignancies obesity associated many cancers breast colorectal liver lung kidney oesophageal pancreatic endometrium ovarian prostate thyroid gallbladder cancer conclusions light information study supports claimed statement obesity one major health problems 21st century considering increase number obese people worldwide necessary develop strategy allowing prevent fighting unhealthy lifestyle order reduce overweight obesity society may essential impact decreasing number incidences cancer pubmed","probabilities":0.7966102,"Title":"Obesity as a tumour development triggering factor","Abstract":"INTRODUCTION: The overweight and obesity epidemic represents a rapidly growing threat to the health of populations in an increasing number of countries. Nearly one-third of the world's population has excess adipose tissue. Nowadays, obesity occurrence is so common that it is replacing more traditional problems, such as an undernutrition and infectious diseases, as the most significant causes of ill health. If the current trend continues, almost half of the world's adult population will be overweight or obese by 2030. OBJECTIVE: The aim of this study is to show the connection between recent trends in body mass index, and the globally changing cancer profile. STATE OF KNOWLEDGE: A range of clinical and epidemiological studies have shown the relationship between excess body fat and the most frequently occurring malignancies. Obesity is associated with many cancers, such as: breast, colorectal, liver, lung, kidney, oesophageal, pancreatic, endometrium, ovarian, prostate, thyroid, and gallbladder cancer. CONCLUSIONS: In the light of this information, the study supports the claimed statement that obesity is one of the major health problems of the 21st century. Considering the increase in the number of obese people worldwide, it is necessary to develop a strategy allowing to prevent it. Fighting against unhealthy lifestyle in order to reduce overweight and obesity in society may have an essential impact on decreasing the number of incidences of cancer.","Source":"PubMed","category":"HUMAN","training_data":"Obesity as a tumour development triggering factor INTRODUCTION: The overweight and obesity epidemic represents a rapidly growing threat to the health of populations in an increasing number of countries. Nearly one-third of the world's population has excess adipose tissue. Nowadays, obesity occurrence is so common that it is replacing more traditional problems, such as an undernutrition and infectious diseases, as the most significant causes of ill health. If the current trend continues, almost half of the world's adult population will be overweight or obese by 2030. OBJECTIVE: The aim of this study is to show the connection between recent trends in body mass index, and the globally changing cancer profile. STATE OF KNOWLEDGE: A range of clinical and epidemiological studies have shown the relationship between excess body fat and the most frequently occurring malignancies. Obesity is associated with many cancers, such as: breast, colorectal, liver, lung, kidney, oesophageal, pancreatic, endometrium, ovarian, prostate, thyroid, and gallbladder cancer. CONCLUSIONS: In the light of this information, the study supports the claimed statement that obesity is one of the major health problems of the 21st century. Considering the increase in the number of obese people worldwide, it is necessary to develop a strategy allowing to prevent it. Fighting against unhealthy lifestyle in order to reduce overweight and obesity in society may have an essential impact on decreasing the number of incidences of cancer. PubMed","prediction_labels":"HUMAN"},{"cleaned":"forty year trends cholangiocarcinoma incidence us intrahepatic disease rise background challenges diagnosis classification cholangiocarcinoma made difficult quantify true incidence highly aggressive malignancy methods analyzed surveillance epidemiology end results data assess long term trends age standardized incidence intrahepatic extrahepatic cholangiocarcinoma 1973 2012 correcting systematic coding errors intrahepatic cholangiocarcinoma icc may frequently misdiagnosed cancer unknown primary cup also analyzed trends incidence cup results 1973 2012 reported u incidence icc increased 0 44 1 18 cases per 100 000 representing annual percentage change apc 2 30 trend accelerated past decade apc 4 36 incidence extrahepatic cholangiocarcinoma increased modestly 0 95 1 02 per 100 000 40 year period apc 0 14 incidence cup histologic features potentially consistent cholangiocarcinoma decreased 51 1973 2012 apc 1 87 whereas incidence cup squamous nonepithelial histologic features increased modestly apc 0 42 conclusion recognized incidence icc u continues rise whereas incidence ecc stable incidence cup fallen dramatically time period implications practice clinical distinctions cholangiocarcinoma particularly intrahepatic cholangiocarcinoma icc cancer unknown primary cup challenging recent discoveries identified recurrent potentially targetable genomic abnormalities icc highlighting importance improving diagnosis study demonstrates incidence icc increasing u whereas incidence extrahepatic cholangiocarcinoma stable concomitantly incidence cup declined dramatically suggesting improved distinction icc cup may major driver increasing recognized incidence icc increasing incidence icc warrants study prevention treatment approaches stn","probabilities":0.9799733,"Title":"Forty-Year Trends In Cholangiocarcinoma Incidence In The Us: Intrahepatic Disease On The Rise","Abstract":"Background: Challenges in the diagnosis and classification of cholangiocarcinoma have made it difficult to quantify the true incidence of this highly aggressive malignancy. \n\n Methods: We analyzed the Surveillance, Epidemiology, and End Results data to assess long-term trends in the age-standardized incidence of intrahepatic and extrahepatic cholangiocarcinoma between 1973 and 2012, correcting for systematic coding errors. Because intrahepatic cholangiocarcinoma (ICC) may frequently be misdiagnosed as cancer of unknown primary (CUP), we also analyzed trends in the incidence of CUP. \n\n Results: Between 1973 and 2012, the reported U.S. incidence of ICC increased from 0.44 to 1.18 cases per 100,000, representing an annual percentage change (APC) of 2.30%; this trend has accelerated during the past decade to an APC of 4.36%. The incidence of extrahepatic cholangiocarcinoma increased modestly from 0.95 to 1.02 per 100,000 during the 40-year period (APC, 0.14%). The incidence of CUP with histologic features potentially consistent with cholangiocarcinoma decreased by 51% between 1973 and 2012 (APC, -1.87%), whereas the incidence of CUP with squamous or nonepithelial histologic features increased modestly (APC, 0.42%). \n\n Conclusion: The recognized incidence of ICC in the U.S. continues to rise, whereas the incidence of ECC is stable. The incidence of CUP has fallen dramatically during the same time period. \n\n Implications for practice: Clinical distinctions between cholangiocarcinoma (particularly intrahepatic cholangiocarcinoma [ICC]) and cancer of unknown primary (CUP) can be challenging. Recent discoveries have identified recurrent and potentially targetable genomic abnormalities in ICC, highlighting the importance of improving diagnosis. This study demonstrates that the incidence of ICC is increasing in the U.S., whereas the incidence of extrahepatic cholangiocarcinoma is stable. Concomitantly, the incidence of CUP has declined dramatically, suggesting that improved distinction between ICC and CUP may be a major driver of the increasing recognized incidence of ICC. The increasing incidence of ICC warrants further study of prevention and treatment approaches.","Source":"STN","category":"HUMAN","training_data":"Forty-Year Trends In Cholangiocarcinoma Incidence In The Us: Intrahepatic Disease On The Rise Background: Challenges in the diagnosis and classification of cholangiocarcinoma have made it difficult to quantify the true incidence of this highly aggressive malignancy. \n\n Methods: We analyzed the Surveillance, Epidemiology, and End Results data to assess long-term trends in the age-standardized incidence of intrahepatic and extrahepatic cholangiocarcinoma between 1973 and 2012, correcting for systematic coding errors. Because intrahepatic cholangiocarcinoma (ICC) may frequently be misdiagnosed as cancer of unknown primary (CUP), we also analyzed trends in the incidence of CUP. \n\n Results: Between 1973 and 2012, the reported U.S. incidence of ICC increased from 0.44 to 1.18 cases per 100,000, representing an annual percentage change (APC) of 2.30%; this trend has accelerated during the past decade to an APC of 4.36%. The incidence of extrahepatic cholangiocarcinoma increased modestly from 0.95 to 1.02 per 100,000 during the 40-year period (APC, 0.14%). The incidence of CUP with histologic features potentially consistent with cholangiocarcinoma decreased by 51% between 1973 and 2012 (APC, -1.87%), whereas the incidence of CUP with squamous or nonepithelial histologic features increased modestly (APC, 0.42%). \n\n Conclusion: The recognized incidence of ICC in the U.S. continues to rise, whereas the incidence of ECC is stable. The incidence of CUP has fallen dramatically during the same time period. \n\n Implications for practice: Clinical distinctions between cholangiocarcinoma (particularly intrahepatic cholangiocarcinoma [ICC]) and cancer of unknown primary (CUP) can be challenging. Recent discoveries have identified recurrent and potentially targetable genomic abnormalities in ICC, highlighting the importance of improving diagnosis. This study demonstrates that the incidence of ICC is increasing in the U.S., whereas the incidence of extrahepatic cholangiocarcinoma is stable. Concomitantly, the incidence of CUP has declined dramatically, suggesting that improved distinction between ICC and CUP may be a major driver of the increasing recognized incidence of ICC. The increasing incidence of ICC warrants further study of prevention and treatment approaches. STN","prediction_labels":"HUMAN"},{"cleaned":"long term survival resection perihilar cholangiocarcinoma impact uicc staging surgical procedure background aims perihilar cholangiocarcinoma rare disease unfavorable prognosis resulting low survival rates study aims retrospectively assess beneficial histopathological features surgical procedures long term survivors e patients surviving perihilar cholangiocarcinoma least 2 y material methods total 322 patients perihilar cholangiocarcinoma underwent surgery center follow ended 2017 76 patients survived 2 y type resection uicc stage histopathological features compared three survival groups 2 3 3 5 5 y results 5 year survival rate selected study cohort 43 4 3 5 y 31 6 2 3 y 25 0 14 5 patients survived 10 y surgery patients non regional lymph node positive tumors distant metastasis e uicc stage ivb p 0 0112 r2 status p 0 0288 exploratory laparotomy p 0 0157 showed poorest survival rates perineural invasion significant impact overall survival however 29 0 patients surviving 5 y displayed lowest perineural infiltration prevalence interestingly bismuth corlette stage iiia p 0 0467 especially caudate lobectomy p 0 0034 associated disease specific overall survival 5y conclusion complete extended tumor resection additional caudate lobe resection strongly associated long term survival perineural infiltration negative prognostic marker prolonged survival needs evaluated larger study cohorts stn","probabilities":0.9799733,"Title":"Long-Term Survival After Resection For Perihilar Cholangiocarcinoma: Impact Of Uicc Staging And Surgical Procedure","Abstract":"Background/aims: Perihilar cholangiocarcinoma is a rare disease with unfavorable prognosis resulting in low survival rates. This study aims to retrospectively assess the beneficial histopathological features and surgical procedures in long-term survivors (i.e., patients surviving perihilar cholangiocarcinoma for at least 2 y). \r\n\r\n Material and methods: In total, 322 patients with perihilar cholangiocarcinoma underwent surgery at our center. The follow-up ended in 2017; 76 patients survived for >2 y. The type of resection, UICC stage, and histopathological features were compared between three survival groups (>2-3, >3-5, and >5 y). \r\n\r\n Results: The >5-year-survival rate in our selected study cohort was 43.4% (>3-5 y,31.6% and >2-3 y, 25.0%), and 14.5% of the patients survived for >10 y after surgery. Patients with non-regional lymph node positive tumors and/or distant metastasis (i.e., UICC stage IVb; p=0.0112), R2 status (p=0.0288), and exploratory laparotomy only (p=0.0157) showed the poorest survival rates. Perineural invasion had no significant impact on the overall survival. However, 29.0% patients surviving for >5 y displayed the lowest perineural infiltration prevalence. Interestingly, Bismuth-Corlette stage IIIa (p=0.0467), especially caudate lobectomy (p=0.0034), was associated with disease-specific overall survival of >5y. \r\n\r\n Conclusion: Complete/extended tumor resection with additional caudate lobe resection is strongly associated with long-term survival. Perineural infiltration as a negative prognostic marker for prolonged survival needs to be evaluated in larger study cohorts.","Source":"STN","category":"HUMAN","training_data":"Long-Term Survival After Resection For Perihilar Cholangiocarcinoma: Impact Of Uicc Staging And Surgical Procedure Background/aims: Perihilar cholangiocarcinoma is a rare disease with unfavorable prognosis resulting in low survival rates. This study aims to retrospectively assess the beneficial histopathological features and surgical procedures in long-term survivors (i.e., patients surviving perihilar cholangiocarcinoma for at least 2 y). \r\n\r\n Material and methods: In total, 322 patients with perihilar cholangiocarcinoma underwent surgery at our center. The follow-up ended in 2017; 76 patients survived for >2 y. The type of resection, UICC stage, and histopathological features were compared between three survival groups (>2-3, >3-5, and >5 y). \r\n\r\n Results: The >5-year-survival rate in our selected study cohort was 43.4% (>3-5 y,31.6% and >2-3 y, 25.0%), and 14.5% of the patients survived for >10 y after surgery. Patients with non-regional lymph node positive tumors and/or distant metastasis (i.e., UICC stage IVb; p=0.0112), R2 status (p=0.0288), and exploratory laparotomy only (p=0.0157) showed the poorest survival rates. Perineural invasion had no significant impact on the overall survival. However, 29.0% patients surviving for >5 y displayed the lowest perineural infiltration prevalence. Interestingly, Bismuth-Corlette stage IIIa (p=0.0467), especially caudate lobectomy (p=0.0034), was associated with disease-specific overall survival of >5y. \r\n\r\n Conclusion: Complete/extended tumor resection with additional caudate lobe resection is strongly associated with long-term survival. Perineural infiltration as a negative prognostic marker for prolonged survival needs to be evaluated in larger study cohorts. STN","prediction_labels":"HUMAN"},{"cleaned":"four microrna signature correlates improved survival cholangiocarcinoma introduction cholangiocarcinoma cc increasing incidence dismal prognosis complete surgical resection offers chance cure even complete resection remains disparity survival recurrence death early stage patients micrornas mirnas small non coding rnas involved gene regulation several mirnas linked cancer progression prognosis employed mirna microarray technology identify mirnas predict survival method mirna extracted 30 archival formalin xed paraf n embedded cc samples samples labeled cy3 hybridised agilent human mirna slides microarray contained probes 866 human mirnas slides scanned 5 micron raw intensities extracted using feature extraction software agilent data analysed within r statistical environment results 30 cases included 10 perihilar cc 19 extrahepatic cc 1 gallbladder carcinoma cases operatively treated macroscopically complete resections data analysis mirna expression revealed mirna expression signature consisting 4 mirnas hsa mir 765 hsa mir 1471 hsa mir 345 hsa mir 663 correlated overall survival 4 mirnas protective e higher expression lowered risk improved survival lower expression increased risk led poorer survival expression data 4 mirnas used calculate risk factor patient allowed assign patients low risk high expression signature high risk low expression signature group respectively two groups showed median survival 15 7 months vs 35 6 months p 0 00016 hazard ratio 1 71 95 con dence interval 1 26 2 34 conclusions despite complete surgical resection patients still exhibit poor survival cc identi ed mirna signature comprising four mirnas predictive survival cc following complete surgical resection google scholar","probabilities":1.0,"Title":"A Four Microrna Signature Correlates With Improved Survival In Cholangiocarcinoma","Abstract":"Introduction: Cholangiocarcinoma (CC) is increasing in incidence and has a dismal prognosis. Complete surgical resection offers the only chance of cure. Even with complete resection there remains a disparity in survival, with recurrence and death at an early stage in some patients. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in gene regulation. Several miRNAs have been linked to cancer progression and prognosis. We employed miRNA microarray technology to identify miRNAs that can predict survival. Method: MiRNA was extracted from 30 archival formalin-fixed paraffin-embedded CC samples. Samples were labeled with Cy3 and hybridised to Agilent Human miRNA slides, each microarray contained probes for 866 human miRNAs. Slides were scanned at 5 micron, raw intensities were extracted using Feature Extraction software (Agilent). Data was analysed within the R statistical environment. Results: The 30 cases included: 10 perihilar CC; 19 extrahepatic CC; and 1 gallbladder carcinoma. All cases were operatively treated with macroscopically complete resections. Data analysis of miRNA expression revealed that a miRNA expression signature consisting of 4 miRNAs (hsa-miR-765, hsa-miR-1471, hsa-miR-345, and hsa-miR-663) that correlated with overall survival. The 4 miRNAs were ”protective” i.e. higher expression lowered the risk and improved survival and lower expression increased the risk and led to poorer survival. The expression data for all 4 miRNAs were used to calculate a risk factor for each patient that allowed to assign the patients to a low-risk (high expression of the signature) and a high-risk (low expression of the signature) group, respectively. The two groups showed a median survival of 15.7 months vs. 35.6 months: p = 0.00016, hazard ratio 1.71 (95% confidence interval 1.26–2.34). Conclusions: Despite complete surgical resection, some patients still exhibit poor survival with CC. We have identified a miRNA signature comprising of four miRNAs that is predictive of survival in CC following complete surgical resection.","Source":"Google Scholar","category":"ANIMAL","training_data":"A Four Microrna Signature Correlates With Improved Survival In Cholangiocarcinoma Introduction: Cholangiocarcinoma (CC) is increasing in incidence and has a dismal prognosis. Complete surgical resection offers the only chance of cure. Even with complete resection there remains a disparity in survival, with recurrence and death at an early stage in some patients. MicroRNAs (miRNAs) are small non-coding RNAs that are involved in gene regulation. Several miRNAs have been linked to cancer progression and prognosis. We employed miRNA microarray technology to identify miRNAs that can predict survival. Method: MiRNA was extracted from 30 archival formalin-fixed paraffin-embedded CC samples. Samples were labeled with Cy3 and hybridised to Agilent Human miRNA slides, each microarray contained probes for 866 human miRNAs. Slides were scanned at 5 micron, raw intensities were extracted using Feature Extraction software (Agilent). Data was analysed within the R statistical environment. Results: The 30 cases included: 10 perihilar CC; 19 extrahepatic CC; and 1 gallbladder carcinoma. All cases were operatively treated with macroscopically complete resections. Data analysis of miRNA expression revealed that a miRNA expression signature consisting of 4 miRNAs (hsa-miR-765, hsa-miR-1471, hsa-miR-345, and hsa-miR-663) that correlated with overall survival. The 4 miRNAs were ”protective” i.e. higher expression lowered the risk and improved survival and lower expression increased the risk and led to poorer survival. The expression data for all 4 miRNAs were used to calculate a risk factor for each patient that allowed to assign the patients to a low-risk (high expression of the signature) and a high-risk (low expression of the signature) group, respectively. The two groups showed a median survival of 15.7 months vs. 35.6 months: p = 0.00016, hazard ratio 1.71 (95% confidence interval 1.26–2.34). Conclusions: Despite complete surgical resection, some patients still exhibit poor survival with CC. We have identified a miRNA signature comprising of four miRNAs that is predictive of survival in CC following complete surgical resection. Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"clinical value serum ca19 9 prognostic factor ampulla vater carcinoma background aims ampulla vater carcinoma relatively rare digestive tract tumor postoperative prognostic factors well studied however indicator preoperative prognosis remains poorly identified study aims identify serum tumor markers preoperative prognostic factors variables postoperative prognostic factors ampulla vater carcinoma methodology study retrospectively analyzed data 26 patients undergoing pancreaticoduodenectomy pd including pylorus preserving pd ampulla vater carcinoma april 1993 december 2006 main outcome measures survival rates patients without high levels ca19 9 cea results patients high levels ca19 9 n 12 significantly higher survival rates without n 14 p 0 0027 high levels cea influence cumulative survival rates p 0 4522 histopathological classification independent predictor poor survival rates patients well differentiated adenocarcinoma n 18 significantly higher survival rates moderate poorly differentiated tumors n 12 p 0 0280 factors tumor size lymph node metastasis p 0 4006 invasion pancreas p 0 1156 duodenum p 0 0 3723 vein p 0 4331 lymph vessel p 0 8606 perineural invasion p 0 0 8765 independent indicators poor survival rate conclusions results study indicated high levels ca19 9 histopathological classification significant independent predictors poor survival rates ampulla vater carcinoma pubmed","probabilities":0.9799733,"Title":"Clinical value of serum CA19-9 as a prognostic factor for the ampulla of Vater carcinoma","Abstract":"BACKGROUND/AIMS: Ampulla of Vater carcinoma is a relatively rare digestive tract tumor; postoperative prognostic factors have been well studied. However, any indicator of preoperative prognosis remains poorly identified. This study aims to identify serum tumor markers as preoperative prognostic factors and other variables as postoperative prognostic factors for ampulla of Vater carcinoma. METHODOLOGY: This study retrospectively analyzed data from 26 patients undergoing pancreaticoduodenectomy (PD), including pylorus preserving PD for ampulla of Vater carcinoma between April 1993 and December 2006. The main outcome measures were survival rates of patients with and without high levels of CA19-9 and CEA. RESULTS: Patients with high levels of CA19-9 (n = 12) had significantly higher survival rates than those without (n = 14) (p = 0.0027). High levels of CEA did not influence cumulative survival rates (p = 0.4522). Histopathological classification was an independent predictor of poor survival rates; patients with well differentiated adenocarcinoma (n = 18) had significantly higher survival rates than those with moderate to poorly differentiated tumors (n = 12) (p = 0.0280). Other factors such as tumor size, lymph node metastasis (p = 0.4006), or invasion of pancreas (p = 0.1156), duodenum (p = 0.0.3723), vein (p = 0.4331), and lymph vessel (p = 0.8606), and perineural invasion (p = 0.0.8765) were not an independent indicators of poor survival rate. CONCLUSIONS: The results of our study indicated that high levels of CA19-9 and histopathological classification were significant independent predictors of poor survival rates for the ampulla of Vater carcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Clinical value of serum CA19-9 as a prognostic factor for the ampulla of Vater carcinoma BACKGROUND/AIMS: Ampulla of Vater carcinoma is a relatively rare digestive tract tumor; postoperative prognostic factors have been well studied. However, any indicator of preoperative prognosis remains poorly identified. This study aims to identify serum tumor markers as preoperative prognostic factors and other variables as postoperative prognostic factors for ampulla of Vater carcinoma. METHODOLOGY: This study retrospectively analyzed data from 26 patients undergoing pancreaticoduodenectomy (PD), including pylorus preserving PD for ampulla of Vater carcinoma between April 1993 and December 2006. The main outcome measures were survival rates of patients with and without high levels of CA19-9 and CEA. RESULTS: Patients with high levels of CA19-9 (n = 12) had significantly higher survival rates than those without (n = 14) (p = 0.0027). High levels of CEA did not influence cumulative survival rates (p = 0.4522). Histopathological classification was an independent predictor of poor survival rates; patients with well differentiated adenocarcinoma (n = 18) had significantly higher survival rates than those with moderate to poorly differentiated tumors (n = 12) (p = 0.0280). Other factors such as tumor size, lymph node metastasis (p = 0.4006), or invasion of pancreas (p = 0.1156), duodenum (p = 0.0.3723), vein (p = 0.4331), and lymph vessel (p = 0.8606), and perineural invasion (p = 0.0.8765) were not an independent indicators of poor survival rate. CONCLUSIONS: The results of our study indicated that high levels of CA19-9 and histopathological classification were significant independent predictors of poor survival rates for the ampulla of Vater carcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cytokeratin 17 expression associated poor prognosis gallbladder adenocarcinoma cytokeratin 17 ck17 basal myoepithelial cell keratin poor prognostic marker cancers organs stomach ovary breast well useful diagnostic marker pancreatobiliary adenocarcinoma however expression pattern prognostic significance studied gallbladder adenocarcinoma constructed tissue microarray samples 82 consecutive patients gallbladder adenocarcinoma treated cholecystectomy kangbuk samsung hospital 2000 2011 ck17 expression examined immunohistochemistry correlated clinicopathologic prognostic factors ck17 stained cytoplasm tumor cells immunohistochemical interpretation possible 77 cases among 41 53 2 considered positive using 5 cutoff determined receiver operating characteristic curve area curve 0 656 p 0 021 ck17 expression associated poor tumor differentiation p 0 001 high pt stage p 0 001 presence distant metastasis p 0 036 low disease specific survival rate p 0 001 results indicate ck17 used marker poor prognosis gallbladder adenocarcinoma pubmed","probabilities":1.0,"Title":"Cytokeratin 17 Expression is Associated With Poor Prognosis in Gallbladder Adenocarcinoma","Abstract":"Cytokeratin 17 (CK17), a basal/myoepithelial cell keratin, is a poor prognostic marker for cancers of organs such as the stomach, ovary, and breast as well as a useful diagnostic marker for pancreatobiliary adenocarcinoma. However, its expression pattern and prognostic significance have not been studied in gallbladder adenocarcinoma. We constructed a tissue microarray from samples from 82 consecutive patients with gallbladder adenocarcinoma treated by cholecystectomy at the Kangbuk Samsung Hospital from 2000 to 2011. CK17 expression was examined by immunohistochemistry and correlated with clinicopathologic prognostic factors. CK17 stained the cytoplasm of tumor cells and immunohistochemical interpretation was possible in 77 cases. Among these, 41 (53.2%) were considered positive using a 5% cutoff determined by a receiver operating characteristic curve (area under the curve=0.656, P=0.021). CK17 expression was associated with poor tumor differentiation (P<0.001), high pT stage (P<0.001), presence of distant metastasis (P=0.036), and low disease-specific survival rate (P<0.001). These results indicate that CK17 can be used as a marker for poor prognosis for gallbladder adenocarcinoma.","Source":"PubMed","category":"ANIMAL","training_data":"Cytokeratin 17 Expression is Associated With Poor Prognosis in Gallbladder Adenocarcinoma Cytokeratin 17 (CK17), a basal/myoepithelial cell keratin, is a poor prognostic marker for cancers of organs such as the stomach, ovary, and breast as well as a useful diagnostic marker for pancreatobiliary adenocarcinoma. However, its expression pattern and prognostic significance have not been studied in gallbladder adenocarcinoma. We constructed a tissue microarray from samples from 82 consecutive patients with gallbladder adenocarcinoma treated by cholecystectomy at the Kangbuk Samsung Hospital from 2000 to 2011. CK17 expression was examined by immunohistochemistry and correlated with clinicopathologic prognostic factors. CK17 stained the cytoplasm of tumor cells and immunohistochemical interpretation was possible in 77 cases. Among these, 41 (53.2%) were considered positive using a 5% cutoff determined by a receiver operating characteristic curve (area under the curve=0.656, P=0.021). CK17 expression was associated with poor tumor differentiation (P<0.001), high pT stage (P<0.001), presence of distant metastasis (P=0.036), and low disease-specific survival rate (P<0.001). These results indicate that CK17 can be used as a marker for poor prognosis for gallbladder adenocarcinoma. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"adiposity cancer major anatomical sites umbrella review literature objective evaluate strength validity evidence association adiposity risk developing dying cancer design umbrella review systematic reviews meta analyses data sources pubmed embase cochrane database systematic reviews manual screening retrieved references eligibility criteria systematic reviews meta analyses observational studies evaluated association indices adiposity risk developing dying cancer data synthesis primary analysis focused cohort studies exploring associations continuous measures adiposity evidence graded strong highly suggestive suggestive weak applying criteria included statistical significance random effects summary estimate largest study meta analysis number cancer cases heterogeneity studies 95 prediction intervals small study effects excess significance bias sensitivity analysis credibility ceilings results 204 meta analyses investigated associations seven indices adiposity developing dying 36 primary cancers subtypes 95 meta analyses included cohort studies used continuous scale measure adiposity 12 13 associations nine cancers supported strong evidence increase body mass index associated higher risk developing oesophageal adenocarcinoma colon rectal cancer men biliary tract system pancreatic cancer endometrial cancer premenopausal women kidney cancer multiple myeloma weight gain waist hip circumference ratio associated higher risks postmenopausal breast cancer women never used hormone replacement therapy endometrial cancer respectively increase risk developing cancer every 5 kg m 2 increase body mass index ranged 9 relative risk 1 09 95 confidence interval 1 06 1 13 rectal cancer among men 56 1 56 1 34 1 81 biliary tract system cancer risk postmenopausal breast cancer among women never used hrt increased 11 5 kg weight gain adulthood 1 11 1 09 1 13 risk endometrial cancer increased 21 0 1 increase waist hip ratio 1 21 1 13 1 29 five additional associations supported strong evidence categorical measures adiposity included weight gain colorectal cancer body mass index gallbladder gastric cardia ovarian cancer multiple myeloma mortality conclusions although association adiposity cancer risk extensively studied associations 11 cancers oesophageal adenocarcinoma multiple myeloma cancers gastric cardia colon rectum biliary tract system pancreas breast endometrium ovary kidney supported strong evidence associations genuine substantial uncertainty remains obesity becoming one biggest problems public health evidence strength associated risks may allow finer selection higher risk cancer targeted personalised prevention strategies pubmed","probabilities":0.9799733,"Title":"Adiposity and cancer at major anatomical sites: umbrella review of the literature","Abstract":"Objective To evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer.Design Umbrella review of systematic reviews and meta-analyses.Data sources PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references.Eligibility criteria Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer.Data synthesis Primary analysis focused on cohort studies exploring associations for continuous measures of adiposity. The evidence was graded into strong, highly suggestive, suggestive, or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings.Results 204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m(2) increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality.Conclusions Although the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming one of the biggest problems in public health; evidence on the strength of the associated risks may allow finer selection of those at higher risk of cancer, who could be targeted for personalised prevention strategies.","Source":"PubMed","category":"HUMAN","training_data":"Adiposity and cancer at major anatomical sites: umbrella review of the literature Objective To evaluate the strength and validity of the evidence for the association between adiposity and risk of developing or dying from cancer.Design Umbrella review of systematic reviews and meta-analyses.Data sources PubMed, Embase, Cochrane Database of Systematic Reviews, and manual screening of retrieved references.Eligibility criteria Systematic reviews or meta-analyses of observational studies that evaluated the association between indices of adiposity and risk of developing or dying from cancer.Data synthesis Primary analysis focused on cohort studies exploring associations for continuous measures of adiposity. The evidence was graded into strong, highly suggestive, suggestive, or weak after applying criteria that included the statistical significance of the random effects summary estimate and of the largest study in a meta-analysis, the number of cancer cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings.Results 204 meta-analyses investigated associations between seven indices of adiposity and developing or dying from 36 primary cancers and their subtypes. Of the 95 meta-analyses that included cohort studies and used a continuous scale to measure adiposity, only 12 (13%) associations for nine cancers were supported by strong evidence. An increase in body mass index was associated with a higher risk of developing oesophageal adenocarcinoma; colon and rectal cancer in men; biliary tract system and pancreatic cancer; endometrial cancer in premenopausal women; kidney cancer; and multiple myeloma. Weight gain and waist to hip circumference ratio were associated with higher risks of postmenopausal breast cancer in women who have never used hormone replacement therapy and endometrial cancer, respectively. The increase in the risk of developing cancer for every 5 kg/m(2) increase in body mass index ranged from 9% (relative risk 1.09, 95% confidence interval 1.06 to 1.13) for rectal cancer among men to 56% (1.56, 1.34 to 1.81) for biliary tract system cancer. The risk of postmenopausal breast cancer among women who have never used HRT increased by 11% for each 5 kg of weight gain in adulthood (1.11, 1.09 to 1.13), and the risk of endometrial cancer increased by 21% for each 0.1 increase in waist to hip ratio (1.21, 1.13 to 1.29). Five additional associations were supported by strong evidence when categorical measures of adiposity were included: weight gain with colorectal cancer; body mass index with gallbladder, gastric cardia, and ovarian cancer; and multiple myeloma mortality.Conclusions Although the association of adiposity with cancer risk has been extensively studied, associations for only 11 cancers (oesophageal adenocarcinoma, multiple myeloma, and cancers of the gastric cardia, colon, rectum, biliary tract system, pancreas, breast, endometrium, ovary, and kidney) were supported by strong evidence. Other associations could be genuine, but substantial uncertainty remains. Obesity is becoming one of the biggest problems in public health; evidence on the strength of the associated risks may allow finer selection of those at higher risk of cancer, who could be targeted for personalised prevention strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"cx 4945 induces methuosis cholangiocarcinoma cell lines ck2 independent mechanism cholangiocarcinoma disease poor prognosis increasing incidence hence pressing unmet clinical need new adjuvant treatments protein kinase ck2 previously casein kinase ii ubiquitously expressed protein kinase regulated multiple cancer cell types inhibition ck2 activity using cx 4945 silmitasertib proposed novel treatment multiple disease settings including cholangiocarcinoma show cx 4945 inhibited proliferation cholangiocarcinoma cell lines vitro moreover cx 4945 treatment induced formation cytosolic vacuoles cholangiocarcinoma cell lines cancer cell lines vacuoles contained extracellular fluid neutral ph features characteristic methuosis contrast simultaneous knockdown catalytic subunits protein kinase ck2 using small interfering rna sirna little effect proliferation cholangiocarcinoma cell lines failed induce vacuole formation surprisingly low doses cx 4945 increased invasive properties cholangiocarcinoma cells due upregulation matrix metallopeptidase 7 mmp 7 knockdown ck2 inhibited cell invasion data suggest cx 4945 inhibits cell proliferation induces cell death via ck2 independent pathways moreover increase cell invasion brought cx 4945 treatment suggests drug might increase tumor invasion clinical settings stn","probabilities":0.9467213,"Title":"Cx-4945 Induces Methuosis In Cholangiocarcinoma Cell Lines By A Ck2-Independent Mechanism","Abstract":"Cholangiocarcinoma is a disease with a poor prognosis and increasing incidence and hence there is a pressing unmet clinical need for new adjuvant treatments. Protein kinase CK2 (previously casein kinase II) is a ubiquitously expressed protein kinase that is up-regulated in multiple cancer cell types. The inhibition of CK2 activity using CX-4945 (Silmitasertib) has been proposed as a novel treatment in multiple disease settings including cholangiocarcinoma. Here, we show that CX-4945 inhibited the proliferation of cholangiocarcinoma cell lines in vitro. Moreover, CX-4945 treatment induced the formation of cytosolic vacuoles in cholangiocarcinoma cell lines and other cancer cell lines. The vacuoles contained extracellular fluid and had neutral pH, features characteristic of methuosis. In contrast, simultaneous knockdown of both the α and α' catalytic subunits of protein kinase CK2 using small interfering RNA (siRNA) had little or no effect on the proliferation of cholangiocarcinoma cell lines and failed to induce the vacuole formation. Surprisingly, low doses of CX-4945 increased the invasive properties of cholangiocarcinoma cells due to an upregulation of matrix metallopeptidase 7 (MMP-7), while the knockdown of CK2 inhibited cell invasion. Our data suggest that CX-4945 inhibits cell proliferation and induces cell death via CK2-independent pathways. Moreover, the increase in cell invasion brought about by CX-4945 treatment suggests that this drug might increase tumor invasion in clinical settings.","Source":"STN","category":"ANIMAL","training_data":"Cx-4945 Induces Methuosis In Cholangiocarcinoma Cell Lines By A Ck2-Independent Mechanism Cholangiocarcinoma is a disease with a poor prognosis and increasing incidence and hence there is a pressing unmet clinical need for new adjuvant treatments. Protein kinase CK2 (previously casein kinase II) is a ubiquitously expressed protein kinase that is up-regulated in multiple cancer cell types. The inhibition of CK2 activity using CX-4945 (Silmitasertib) has been proposed as a novel treatment in multiple disease settings including cholangiocarcinoma. Here, we show that CX-4945 inhibited the proliferation of cholangiocarcinoma cell lines in vitro. Moreover, CX-4945 treatment induced the formation of cytosolic vacuoles in cholangiocarcinoma cell lines and other cancer cell lines. The vacuoles contained extracellular fluid and had neutral pH, features characteristic of methuosis. In contrast, simultaneous knockdown of both the α and α' catalytic subunits of protein kinase CK2 using small interfering RNA (siRNA) had little or no effect on the proliferation of cholangiocarcinoma cell lines and failed to induce the vacuole formation. Surprisingly, low doses of CX-4945 increased the invasive properties of cholangiocarcinoma cells due to an upregulation of matrix metallopeptidase 7 (MMP-7), while the knockdown of CK2 inhibited cell invasion. Our data suggest that CX-4945 inhibits cell proliferation and induces cell death via CK2-independent pathways. Moreover, the increase in cell invasion brought about by CX-4945 treatment suggests that this drug might increase tumor invasion in clinical settings. STN","prediction_labels":"ANIMAL"},{"cleaned":"hepatitis c virus infection risk cancer among elderly us adults registry based case control study background hepatitis c virus hcv infection causes hepatocellular carcinoma hcc subtypes non hodgkin lymphoma nhl associations cancers established authors systematically assessed associations hcv infection cancers us elderly population methods registry based case control study using surveillance epidemiology end results seer medicare data us adults aged 66 years cases n 1 623 538 patients first cancers identified seer registries 1993 2011 controls n 200 000 randomly selected cancer free individuals frequency matched cases age sex race calendar year associations hcv documented medicare claims determined using logistic regression results hcv prevalence higher cases controls 0 7 vs 0 5 hcv positively associated cancers liver adjusted odds ratio aor 31 5 95 confidence interval ci 29 0 34 3 intrahepatic bile duct aor 3 40 95 ci 2 52 4 58 extrahepatic bile duct aor 1 90 95 ci 1 41 2 57 pancreas aor 1 23 95 ci 1 09 1 40 anus aor 1 97 95 ci 1 42 2 73 nonmelanoma nonepithelial skin cancer aor 1 53 95 ci 1 15 2 04 myelodysplastic syndrome aor 1 56 95 ci 1 33 1 83 diffuse large b cell lymphoma aor 1 57 95 ci 1 34 1 84 specific skin cancers associated hcv merkel cell carcinoma aor 1 92 95 ci 1 30 2 85 appendageal skin cancers aor 2 02 95 ci 1 29 3 16 inverse associations observed uterine cancer aor 0 64 95 ci 0 51 0 80 prostate cancer aor 0 73 95 ci 0 66 0 82 associations maintained sensitivity analyses conducted among individuals without documented alcohol abuse cirrhosis hepatitis b human immunodeficiency virus infections adjustment socioeconomic status associations hcv cancers observed conclusions hcv associated increased risk cancers hcc us elderly population notably bile duct cancers diffuse large b cell lymphoma results support possible etiologic role hcv expanded group cancers cancer 2017 123 1202 1211 2016 american cancer society pubmed","probabilities":0.962963,"Title":"Hepatitis C virus infection and the risk of cancer among elderly US adults: A registry-based case-control study","Abstract":"BACKGROUND: Hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC) and subtypes of non-Hodgkin lymphoma (NHL). Associations with other cancers are not established. The authors systematically assessed associations between HCV infection and cancers in the US elderly population. METHODS: This was a registry-based case-control study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data in US adults aged ≥66 years. Cases (n = 1,623,538) were patients who had first cancers identified in SEER registries (1993-2011). Controls (n = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race, and calendar year. Associations with HCV (documented by Medicare claims) were determined using logistic regression. RESULTS: HCV prevalence was higher in cases than in controls (0.7% vs 0.5%). HCV was positively associated with cancers of the liver (adjusted odds ratio [aOR] = 31.5; 95% confidence interval [CI], 29.0-34.3), intrahepatic bile duct (aOR, 3.40; 95% CI, 2.52-4.58), extrahepatic bile duct (aOR, 1.90; 95% CI, 1.41-2.57), pancreas (aOR, 1.23; 95% CI, 1.09-1.40), and anus (aOR, 1.97; 95% CI, 1.42-2.73); nonmelanoma nonepithelial skin cancer (aOR, 1.53; 95% CI, 1.15-2.04); myelodysplastic syndrome (aOR, 1.56; 95% CI, 1.33-1.83); and diffuse large B-cell lymphoma (aOR, 1.57; 95% CI, 1.34-1.84). Specific skin cancers associated with HCV were Merkel cell carcinoma (aOR, 1.92; 95% CI, 1.30-2.85) and appendageal skin cancers (aOR, 2.02; 95% CI, 1.29-3.16). Inverse associations were observed with uterine cancer (aOR, 0.64; 95% CI, 0.51-0.80) and prostate cancer (aOR, 0.73; 95% CI, 0.66-0.82). Associations were maintained in sensitivity analyses conducted among individuals without documented alcohol abuse, cirrhosis, or hepatitis B or human immunodeficiency virus infections and after adjustment for socioeconomic status. Associations of HCV with other cancers were not observed. CONCLUSIONS: HCV is associated with increased risk of cancers other than HCC in the US elderly population, notably bile duct cancers and diffuse large B-cell lymphoma. These results support a possible etiologic role for HCV in an expanded group of cancers. Cancer 2017;123:1202-1211. © 2016 American Cancer Society.","Source":"PubMed","category":"HUMAN","training_data":"Hepatitis C virus infection and the risk of cancer among elderly US adults: A registry-based case-control study BACKGROUND: Hepatitis C virus (HCV) infection causes hepatocellular carcinoma (HCC) and subtypes of non-Hodgkin lymphoma (NHL). Associations with other cancers are not established. The authors systematically assessed associations between HCV infection and cancers in the US elderly population. METHODS: This was a registry-based case-control study using Surveillance, Epidemiology, and End Results (SEER)-Medicare data in US adults aged ≥66 years. Cases (n = 1,623,538) were patients who had first cancers identified in SEER registries (1993-2011). Controls (n = 200,000) were randomly selected, cancer-free individuals who were frequency-matched to cases on age, sex, race, and calendar year. Associations with HCV (documented by Medicare claims) were determined using logistic regression. RESULTS: HCV prevalence was higher in cases than in controls (0.7% vs 0.5%). HCV was positively associated with cancers of the liver (adjusted odds ratio [aOR] = 31.5; 95% confidence interval [CI], 29.0-34.3), intrahepatic bile duct (aOR, 3.40; 95% CI, 2.52-4.58), extrahepatic bile duct (aOR, 1.90; 95% CI, 1.41-2.57), pancreas (aOR, 1.23; 95% CI, 1.09-1.40), and anus (aOR, 1.97; 95% CI, 1.42-2.73); nonmelanoma nonepithelial skin cancer (aOR, 1.53; 95% CI, 1.15-2.04); myelodysplastic syndrome (aOR, 1.56; 95% CI, 1.33-1.83); and diffuse large B-cell lymphoma (aOR, 1.57; 95% CI, 1.34-1.84). Specific skin cancers associated with HCV were Merkel cell carcinoma (aOR, 1.92; 95% CI, 1.30-2.85) and appendageal skin cancers (aOR, 2.02; 95% CI, 1.29-3.16). Inverse associations were observed with uterine cancer (aOR, 0.64; 95% CI, 0.51-0.80) and prostate cancer (aOR, 0.73; 95% CI, 0.66-0.82). Associations were maintained in sensitivity analyses conducted among individuals without documented alcohol abuse, cirrhosis, or hepatitis B or human immunodeficiency virus infections and after adjustment for socioeconomic status. Associations of HCV with other cancers were not observed. CONCLUSIONS: HCV is associated with increased risk of cancers other than HCC in the US elderly population, notably bile duct cancers and diffuse large B-cell lymphoma. These results support a possible etiologic role for HCV in an expanded group of cancers. Cancer 2017;123:1202-1211. © 2016 American Cancer Society. PubMed","prediction_labels":"HUMAN"},{"cleaned":"lymphadenectomy staging treatment intrahepatic cholangiocarcinoma population based study using national cancer institute seer database objectives although lymphatic spread common intrahepatic cholangiocarcinoma icc lymphadenectomy widely performed part operative resection disease objectives study assess national trends lymphadenectomy impact survival patients icc methods national cancer institute surveillance epidemiology end results seer registry queried identify patients icc n 4893 reported 1988 2007 kaplan maier cox proportional hazards regression used analyse survival results five year overall survival os 5 2 lymph node ln status available 48 9 n 2391 patients histologic ln evaluation performed 13 5 n 658 patients median two interquartile range 1 3 lns study period frequency histologic ln assessment p 0 78 change liver resection patients 733 resected patients positive vs negative ln status associated worse 5 year os 8 4 vs 25 9 respectively hazard ratio 1 8 p 0 001 conclusions nodal status important prognostic factor survival patients diagnosed icc usa patients undergo hepatic resection lymphadenectomy therefore clinical benefit formal lymphadenectomy icc remains unknown pubmed","probabilities":0.9799733,"Title":"Lymphadenectomy in the staging and treatment of intrahepatic cholangiocarcinoma: a population-based study using the National Cancer Institute SEER database","Abstract":"OBJECTIVES: Although lymphatic spread is common in intrahepatic cholangiocarcinoma (ICC), lymphadenectomy is not widely performed as part of operative resection in this disease. The objectives of this study were to assess national trends for lymphadenectomy and its impact on survival in patients with ICC. METHODS: The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry was queried to identify patients with ICC (n=4893) reported during 1988-2007. Kaplan-Maier and Cox proportional hazards regression were used to analyse survival. RESULTS: Five-year overall survival (OS) was 5.2%. Lymph node (LN) status was available for 48.9% (n=2391) of patients. Histologic LN evaluation was performed in 13.5% (n=658) of patients for a median of two (interquartile range: 1-3) LNs. During the study period, the frequency of histologic LN assessment (P=0.78) did not change in liver resection patients. In the 733 resected patients, positive vs. negative LN status was associated with worse 5-year OS of 8.4% vs. 25.9%, respectively (hazard ratio=1.8; P<0.001). CONCLUSIONS: Nodal status is an important prognostic factor for survival in patients diagnosed with ICC. In the USA, few patients undergo hepatic resection with lymphadenectomy; therefore, the clinical benefit of formal lymphadenectomy in ICC remains unknown.","Source":"PubMed","category":"HUMAN","training_data":"Lymphadenectomy in the staging and treatment of intrahepatic cholangiocarcinoma: a population-based study using the National Cancer Institute SEER database OBJECTIVES: Although lymphatic spread is common in intrahepatic cholangiocarcinoma (ICC), lymphadenectomy is not widely performed as part of operative resection in this disease. The objectives of this study were to assess national trends for lymphadenectomy and its impact on survival in patients with ICC. METHODS: The National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) registry was queried to identify patients with ICC (n=4893) reported during 1988-2007. Kaplan-Maier and Cox proportional hazards regression were used to analyse survival. RESULTS: Five-year overall survival (OS) was 5.2%. Lymph node (LN) status was available for 48.9% (n=2391) of patients. Histologic LN evaluation was performed in 13.5% (n=658) of patients for a median of two (interquartile range: 1-3) LNs. During the study period, the frequency of histologic LN assessment (P=0.78) did not change in liver resection patients. In the 733 resected patients, positive vs. negative LN status was associated with worse 5-year OS of 8.4% vs. 25.9%, respectively (hazard ratio=1.8; P<0.001). CONCLUSIONS: Nodal status is an important prognostic factor for survival in patients diagnosed with ICC. In the USA, few patients undergo hepatic resection with lymphadenectomy; therefore, the clinical benefit of formal lymphadenectomy in ICC remains unknown. PubMed","prediction_labels":"HUMAN"},{"cleaned":"pancreaticoduodenectomy distal cholangiocarcinoma surgical results prognostic factors long term follow purpose prognostic indicators distal cholangiocarcinoma widely confirmed rarity despite early appearance symptoms poor prognosis aim study identify prognostic factors patients undergoing pancreaticoduodenectomy pd distal bile duct cancer dbdc high volume center pancreatic disease methods january 2000 december 2013 1490 pd performed periampullary disease data patients histologically proven cholangiocarcinoma reviewed preoperative data post operative complications pathologic features survival investigated results among 50 histologically proven dbdc 3 3 4 patients underwent cbd resection excluded thus study population consisted 46 patients overall surgical morbidity rate 67 4 mortality nil major complications pancreatic fistula 47 8 abdominal collections 34 8 post pancreatectomy hemorrhage 21 7 delayed gastric emptying 10 9 majority resections r0 73 9 presence metastatic lymph nodes n1 identified 76 1 cases among n1 cases frequently involved lymph nodes pancreaticoduodenal nodes 50 hepatoduodenal ligament nodes 21 7 superior mesenteric artery nodes 8 7 anterior hepatic artery nodes 4 3 overall survival rates 88 8 40 18 1 3 5 years respectively median survival 31 months univariate analysis tumor grading nodal metastasis predictors poor prognosis p 0 05 findings confirmed multivariate analysis conclusions study shows dbdc rare entity even large surgical series reviewed tumor differentiation nodal status confirmed important prognostic factors pancreaticoduodenectomy remains procedure choice order obtain free surgical margins order harvest correct number lymph nodes correct staging pubmed","probabilities":0.9799733,"Title":"Pancreaticoduodenectomy for distal cholangiocarcinoma: surgical results, prognostic factors, and long-term follow-up","Abstract":"PURPOSE: Prognostic indicators for distal cholangiocarcinoma have not been widely confirmed because of its rarity. Despite the early appearance of symptoms, it has a very poor prognosis. The aim of this study was to identify prognostic factors in patients undergoing pancreaticoduodenectomy (PD) for distal bile duct cancer (DBDC) in a high-volume center for pancreatic disease. METHODS: From January 2000 to December 2013, 1490 PD were performed for periampullary disease. Data from all patients with histologically proven cholangiocarcinoma were reviewed. Preoperative data, post-operative complications, pathologic features, and survival were investigated. RESULTS: Among 50 histologically proven DBDC (3.3 %), 4 patients who underwent CBD resection were excluded. Thus, the study population consisted of 46 patients. Overall surgical morbidity rate was 67.4 %; mortality was nil. Major complications were pancreatic fistula (47.8 %), abdominal collections (34.8 %), post-pancreatectomy hemorrhage (21.7 %), and delayed gastric emptying (10.9 %). The majority of resections were R0 (73.9 %). The presence of metastatic lymph nodes (N1) was identified in 76.1 % of cases. Among N1 cases, the most frequently involved lymph nodes were pancreaticoduodenal nodes (50 %), hepatoduodenal ligament nodes (21.7 %), superior mesenteric artery nodes (8.7 %), and anterior hepatic artery nodes (4.3 %). Overall, survival rates were 88.8, 40, and 18 % at 1, 3, and 5 years, respectively. Median survival was 31 months. By univariate analysis, only tumor grading and nodal metastasis were predictors of poor prognosis (p < 0.05). These findings were not confirmed in multivariate analysis. CONCLUSIONS: This study shows that DBDC is a rare entity even if large surgical series are reviewed. Tumor differentiation and nodal status have been confirmed as important prognostic factors. Pancreaticoduodenectomy remains the procedure of choice in order to obtain free surgical margins and in order to harvest the correct number of lymph nodes for a correct staging.","Source":"PubMed","category":"HUMAN","training_data":"Pancreaticoduodenectomy for distal cholangiocarcinoma: surgical results, prognostic factors, and long-term follow-up PURPOSE: Prognostic indicators for distal cholangiocarcinoma have not been widely confirmed because of its rarity. Despite the early appearance of symptoms, it has a very poor prognosis. The aim of this study was to identify prognostic factors in patients undergoing pancreaticoduodenectomy (PD) for distal bile duct cancer (DBDC) in a high-volume center for pancreatic disease. METHODS: From January 2000 to December 2013, 1490 PD were performed for periampullary disease. Data from all patients with histologically proven cholangiocarcinoma were reviewed. Preoperative data, post-operative complications, pathologic features, and survival were investigated. RESULTS: Among 50 histologically proven DBDC (3.3 %), 4 patients who underwent CBD resection were excluded. Thus, the study population consisted of 46 patients. Overall surgical morbidity rate was 67.4 %; mortality was nil. Major complications were pancreatic fistula (47.8 %), abdominal collections (34.8 %), post-pancreatectomy hemorrhage (21.7 %), and delayed gastric emptying (10.9 %). The majority of resections were R0 (73.9 %). The presence of metastatic lymph nodes (N1) was identified in 76.1 % of cases. Among N1 cases, the most frequently involved lymph nodes were pancreaticoduodenal nodes (50 %), hepatoduodenal ligament nodes (21.7 %), superior mesenteric artery nodes (8.7 %), and anterior hepatic artery nodes (4.3 %). Overall, survival rates were 88.8, 40, and 18 % at 1, 3, and 5 years, respectively. Median survival was 31 months. By univariate analysis, only tumor grading and nodal metastasis were predictors of poor prognosis (p < 0.05). These findings were not confirmed in multivariate analysis. CONCLUSIONS: This study shows that DBDC is a rare entity even if large surgical series are reviewed. Tumor differentiation and nodal status have been confirmed as important prognostic factors. Pancreaticoduodenectomy remains the procedure of choice in order to obtain free surgical margins and in order to harvest the correct number of lymph nodes for a correct staging. PubMed","prediction_labels":"HUMAN"},{"cleaned":"anti ny eso 1 autoantibody may tumor marker intrahepatic cholangiocarcinoma anti ny eso 1 antibody observed multitude malignancies study aimed evaluate expression serum anti ny eso 1 antibodies prognostic value intrahepatic cholangiocarcinoma total 103 patients intrahepatic cholangiocarcinoma enrolled study enzyme linked immunosorbent assay elisa performed detect serum level anti ny eso 1 antibody western blotting performed assess ny eso 1 expression tumor adjacent tissues serum ny eso 1 antibody detected 18 4 patients intrahepatic cholangiocarcinoma value significantly higher patients chronic hepatitis b serum ny eso 1 antibody positively correlated tumor differentiation lymphatic metastasis ctnm stage abdominal pain finally higher cumulative survival rate patients serum ny eso 1 positivity serum ny eso 1 negativity among patients stage iii iv data uncovered ny eso 1 antibody might helpful tumor marker prognostic predictor intrahepatic cholangiocarcinoma stn","probabilities":0.7777778,"Title":"Anti-Ny-Eso-1 Autoantibody May Be A Tumor Marker For Intrahepatic Cholangiocarcinoma","Abstract":"Anti-NY-ESO-1 antibody is observed in a multitude of malignancies. This study was aimed to evaluate the expression of serum anti-NY-ESO-1 antibodies and its prognostic value in intrahepatic cholangiocarcinoma. A total of 103 patients with intrahepatic cholangiocarcinoma were enrolled in the study. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum level of anti-NY-ESO-1 antibody. Western blotting was performed to assess the NY-ESO-1 expression in tumor and adjacent tissues. The serum NY-ESO-1 antibody was detected in 18.4% of patients with intrahepatic cholangiocarcinoma, a value that was significantly higher than that in patients with chronic Hepatitis B. Serum NY-ESO-1 antibody was positively correlated with tumor differentiation, lymphatic metastasis, cTNM stage and abdominal pain. Finally, there was a higher cumulative survival rate in patients with serum NY-ESO-1 positivity than in those with serum NY-ESO-1 negativity among the patients with stage III + IV. Our data uncovered that NY-ESO-1 antibody might be a helpful tumor marker and prognostic predictor in intrahepatic cholangiocarcinoma.","Source":"STN","category":"HUMAN","training_data":"Anti-Ny-Eso-1 Autoantibody May Be A Tumor Marker For Intrahepatic Cholangiocarcinoma Anti-NY-ESO-1 antibody is observed in a multitude of malignancies. This study was aimed to evaluate the expression of serum anti-NY-ESO-1 antibodies and its prognostic value in intrahepatic cholangiocarcinoma. A total of 103 patients with intrahepatic cholangiocarcinoma were enrolled in the study. Enzyme-linked immunosorbent assay (ELISA) was performed to detect the serum level of anti-NY-ESO-1 antibody. Western blotting was performed to assess the NY-ESO-1 expression in tumor and adjacent tissues. The serum NY-ESO-1 antibody was detected in 18.4% of patients with intrahepatic cholangiocarcinoma, a value that was significantly higher than that in patients with chronic Hepatitis B. Serum NY-ESO-1 antibody was positively correlated with tumor differentiation, lymphatic metastasis, cTNM stage and abdominal pain. Finally, there was a higher cumulative survival rate in patients with serum NY-ESO-1 positivity than in those with serum NY-ESO-1 negativity among the patients with stage III + IV. Our data uncovered that NY-ESO-1 antibody might be a helpful tumor marker and prognostic predictor in intrahepatic cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"long term survival hilar cholangiocarcinoma also possible unresectable patients background radical resection remains curative treatment hilar cholangiocarcinoma hcca limited proportion patients however eligible resection survival prognostic factors patients largely unknown aim study evaluate survival prognostic factors unresectable patients presenting hcca methods performed cohort study denominator hcca patients seen tertiary referral center march 2003 march 2009 demographics treatment pathology results survival analyzed results total 217 patients suspected hcca identified ninety five patients 40 underwent laparotomy 57 63 patients resection performed overall median 5 year survival resected patients 37 months 43 respectively compared 13 months 7 unresectable patients unresectable patients median survival better patients locally advanced disease 16 months compared patients hepatic extrahepatic metastases 5 3 months p 0 001 160 unresectable patients 17 10 survived longer 3 years conclusion patients presenting hcca center 26 proved resectable 7 long term survival rate unresectable patients remarkable emphasizes indolent growth tumors patients metastases much worse prognosis median 4 months stn","probabilities":0.9799733,"Title":"Long-Term Survival In Hilar Cholangiocarcinoma Also Possible In Unresectable Patients","Abstract":"Background: Radical resection remains the only curative treatment for hilar cholangiocarcinoma (HCCA). Only a limited proportion of patients, however, are eligible for resection. The survival and prognostic factors of these patients are largely unknown. The aim of this study was to evaluate survival and prognostic factors in unresectable patients presenting with HCCA. \r\n\r\n Methods: We performed a cohort study of the denominator of HCCA patients seen in a tertiary referral center between March 2003 and March 2009. Demographics, treatment, pathology results, and survival were analyzed. \r\n\r\n Results: A total of 217 patients with suspected HCCA were identified. Ninety-five patients (40 %) underwent laparotomy, and in 57 (63 %) of these patients resection was performed. Overall median and 5-year survival of resected patients were 37 months and 43 %, respectively, as compared to 13 months and 7 % in unresectable patients. In unresectable patients, median survival was better in patients with locally advanced disease (16 months) as compared to patients with hepatic and extrahepatic metastases (5 and 3 months, p < 0.001). Of the 160 unresectable patients, 17 (10 %) survived longer than 3 years. \r\n\r\n Conclusion: Of the patients presenting with HCCA in our center, 26 % proved resectable. The 7 % long-term survival rate of unresectable patients is remarkable and emphasizes the indolent growth of some of these tumors. Patients with metastases had a much worse prognosis with a median of 4 months.","Source":"STN","category":"HUMAN","training_data":"Long-Term Survival In Hilar Cholangiocarcinoma Also Possible In Unresectable Patients Background: Radical resection remains the only curative treatment for hilar cholangiocarcinoma (HCCA). Only a limited proportion of patients, however, are eligible for resection. The survival and prognostic factors of these patients are largely unknown. The aim of this study was to evaluate survival and prognostic factors in unresectable patients presenting with HCCA. \r\n\r\n Methods: We performed a cohort study of the denominator of HCCA patients seen in a tertiary referral center between March 2003 and March 2009. Demographics, treatment, pathology results, and survival were analyzed. \r\n\r\n Results: A total of 217 patients with suspected HCCA were identified. Ninety-five patients (40 %) underwent laparotomy, and in 57 (63 %) of these patients resection was performed. Overall median and 5-year survival of resected patients were 37 months and 43 %, respectively, as compared to 13 months and 7 % in unresectable patients. In unresectable patients, median survival was better in patients with locally advanced disease (16 months) as compared to patients with hepatic and extrahepatic metastases (5 and 3 months, p < 0.001). Of the 160 unresectable patients, 17 (10 %) survived longer than 3 years. \r\n\r\n Conclusion: Of the patients presenting with HCCA in our center, 26 % proved resectable. The 7 % long-term survival rate of unresectable patients is remarkable and emphasizes the indolent growth of some of these tumors. Patients with metastases had a much worse prognosis with a median of 4 months. STN","prediction_labels":"HUMAN"},{"cleaned":"high mir 224 expression cholangiocarcinoma may predict survival abstract available google scholar","probabilities":0.9799733,"Title":"High Mir-224 Expression In Cholangiocarcinoma May Predict Survival","Abstract":"Abstract not available","Source":"Google Scholar","category":"HUMAN","training_data":"High Mir-224 Expression In Cholangiocarcinoma May Predict Survival Abstract not available Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"impact neoadjuvant chemoradiation tumor burden liver transplantation unresectable cholangiocarcinoma early experience liver transplantation lt cholangiocarcinoma cc dismal poor survival outcomes high recurrence rates however lt cc conjunction neoadjuvant chemoradiation recently shown encouraging results although data extremely limited institution 2001 2008 22 cc patients underwent protocol orthotopic lt median age 45 years range 24 63 years median follow 601 5 days range 111 1388 days median survival time cohort 3 3 years 1 2 3 year kaplan meier survival probabilities 90 70 63 respectively whereas historical 5 year survival rates 0 18 intrahepatic cc 23 26 extrahepatic cc patients underwent transplantation without neoadjuvant therapy encouraging survival rates patients type tumor difficult diagnose treat less significant compared national 1 3 year survival rates 86 68 respectively patients undergoing deceased donor lt malignant neoplasms liver reported united network organ sharing series disease recurrence significantly associated larger residual tumor 6 3 versus 2 0 cm mean values p 0 008 shorter waiting time lt chemoradiation protocol 18 versus 56 days mean values p 0 04 lt protocol cc found promising patients truly extrahepatic cc patients within stages iib american joint committee cancer staging system 100 survival median follow 2 2 years results notably poor patients stage iii extrahepatic cc median survival 1 2 years observations highlight need accurate preoperative staging cc ideal lt recipient selection importance low tumor burden longer wait neoadjuvant therapy effective chemoradiation regimens reducing tumor burden appropriate timing lt neoadjuvant chemoradiation require research stn","probabilities":0.9799733,"Title":"Impact Of Neoadjuvant Chemoradiation On The Tumor Burden Before Liver Transplantation For Unresectable Cholangiocarcinoma","Abstract":"The very early experience with liver transplantation (LT) for cholangiocarcinoma (CC) was dismal because of the poor survival outcomes and the high recurrence rates. However, LT for CC in conjunction with neoadjuvant chemoradiation recently has shown encouraging results, although the data are extremely limited. At our institution between 2001 and 2008, 22 CC patients underwent protocol orthotopic LT at a median age of 45 years (range = 24-63 years). At a median follow-up of 601.5 days (range = 111-1388 days), the median survival time of the cohort was 3.3 years. The 1-, 2-, and 3-year Kaplan-Meier survival probabilities were 90%, 70%, and 63%, respectively, whereas the historical 5-year survival rates were 0% to 18% for intrahepatic CC and 23% to 26% for extrahepatic CC when patients underwent transplantation without neoadjuvant therapy. These encouraging survival rates for patients with this type of tumor, which is difficult to diagnose and treat, are no less significant when they are compared to the national 1- and 3-year survival rates (86% and 68%, respectively) of patients undergoing deceased donor LT for malignant neoplasms of the liver (as reported by the United Network for Organ Sharing). In our series, disease recurrence was significantly associated with a larger residual tumor [6.3 versus 2.0 cm (mean values), P = 0.008] and with a shorter waiting time for LT after the chemoradiation protocol [18 versus 56 days (mean values), P = 0.04]. Our LT protocol for CC was found to be promising for patients with truly extrahepatic CC and for patients within stages I to IIB of the American Joint Committee on Cancer Staging system (100% survival at a median follow-up of 2.2 years), but the results were notably poor for patients with stage III extrahepatic CC (median survival = 1.2 years). These observations highlight the need for accurate preoperative staging of CC for ideal LT recipient selection and the importance of a low tumor burden and a longer wait after neoadjuvant therapy. More effective chemoradiation regimens for reducing the tumor burden and the appropriate timing of LT after neoadjuvant chemoradiation require further research.","Source":"STN","category":"HUMAN","training_data":"Impact Of Neoadjuvant Chemoradiation On The Tumor Burden Before Liver Transplantation For Unresectable Cholangiocarcinoma The very early experience with liver transplantation (LT) for cholangiocarcinoma (CC) was dismal because of the poor survival outcomes and the high recurrence rates. However, LT for CC in conjunction with neoadjuvant chemoradiation recently has shown encouraging results, although the data are extremely limited. At our institution between 2001 and 2008, 22 CC patients underwent protocol orthotopic LT at a median age of 45 years (range = 24-63 years). At a median follow-up of 601.5 days (range = 111-1388 days), the median survival time of the cohort was 3.3 years. The 1-, 2-, and 3-year Kaplan-Meier survival probabilities were 90%, 70%, and 63%, respectively, whereas the historical 5-year survival rates were 0% to 18% for intrahepatic CC and 23% to 26% for extrahepatic CC when patients underwent transplantation without neoadjuvant therapy. These encouraging survival rates for patients with this type of tumor, which is difficult to diagnose and treat, are no less significant when they are compared to the national 1- and 3-year survival rates (86% and 68%, respectively) of patients undergoing deceased donor LT for malignant neoplasms of the liver (as reported by the United Network for Organ Sharing). In our series, disease recurrence was significantly associated with a larger residual tumor [6.3 versus 2.0 cm (mean values), P = 0.008] and with a shorter waiting time for LT after the chemoradiation protocol [18 versus 56 days (mean values), P = 0.04]. Our LT protocol for CC was found to be promising for patients with truly extrahepatic CC and for patients within stages I to IIB of the American Joint Committee on Cancer Staging system (100% survival at a median follow-up of 2.2 years), but the results were notably poor for patients with stage III extrahepatic CC (median survival = 1.2 years). These observations highlight the need for accurate preoperative staging of CC for ideal LT recipient selection and the importance of a low tumor burden and a longer wait after neoadjuvant therapy. More effective chemoradiation regimens for reducing the tumor burden and the appropriate timing of LT after neoadjuvant chemoradiation require further research. STN","prediction_labels":"HUMAN"},{"cleaned":"proteomic analysis differentially expressed proteins peripheral cholangiocarcinoma cholangiocarcinoma adenocarcinoma liver increased incidence last thirty years reach similar levels liver cancers diagnosis disease usually late prognosis poor therefore great importance identify novel candidate markers potential early indicators disease well molecules may potential therapeutic targets used proteomic approach identify differentially expressed proteins peripheral cholangiocarcinoma cases compared expression paired non tumoral liver tissue patients two dimensional fluorescence difference gel electrophoresis labeling proteins cyanines 3 5 used identify differentially expressed proteins overall approximately 2 400 protein spots visualised gel 172 protein spots showed significant differences expression level tumoral non tumoral tissue p 0 01 100 spots corresponding 138 different proteins identified mass spectrometry 70 proteins expressed whereas 68 proteins expressed tumoral samples compared non tumoral samples among expressed proteins immunohistochemistry studies confirmed increased expression 14 3 3 protein tumoral cells smooth muscle actin periostin shown overexpressed stromal myofibroblasts surrounding tumoral cells smooth muscle actin marker myofibroblast differentiation found prognostic indicator colon cancer periostin may also role cell adhesion proliferation migration identified cancers underlines role stromal components cancer progression interest developing new diagnostic therapeutic tools stn","probabilities":0.9467213,"Title":"Proteomic Analysis Of Differentially Expressed Proteins In Peripheral Cholangiocarcinoma","Abstract":"Cholangiocarcinoma is an adenocarcinoma of the liver which has increased in incidence over the last thirty years to reach similar levels to other liver cancers. Diagnosis of this disease is usually late and prognosis is poor, therefore it is of great importance to identify novel candidate markers and potential early indicators of this disease as well as molecules that may be potential therapeutic targets. We have used a proteomic approach to identify differentially expressed proteins in peripheral cholangiocarcinoma cases and compared expression with paired non-tumoral liver tissue from the same patients. Two-dimensional fluorescence difference gel electrophoresis after labeling of the proteins with cyanines 3 and 5 was used to identify differentially expressed proteins. Overall, of the approximately 2,400 protein spots visualised in each gel, 172 protein spots showed significant differences in expression level between tumoral and non-tumoral tissue with p < 0.01. Of these, 100 spots corresponding to 138 different proteins were identified by mass spectrometry: 70 proteins were over-expressed whereas 68 proteins were under-expressed in tumoral samples compared to non-tumoral samples. Among the over-expressed proteins, immunohistochemistry studies confirmed an increased expression of 14-3-3 protein in tumoral cells while α-smooth muscle actin and periostin were shown to be overexpressed in the stromal myofibroblasts surrounding tumoral cells. α-Smooth muscle actin is a marker of myofibroblast differentiation and has been found to be a prognostic indicator in colon cancer while periostin may also have a role in cell adhesion, proliferation and migration and has been identified in other cancers. This underlines the role of stromal components in cancer progression and their interest for developing new diagnostic or therapeutic tools.","Source":"STN","category":"ANIMAL","training_data":"Proteomic Analysis Of Differentially Expressed Proteins In Peripheral Cholangiocarcinoma Cholangiocarcinoma is an adenocarcinoma of the liver which has increased in incidence over the last thirty years to reach similar levels to other liver cancers. Diagnosis of this disease is usually late and prognosis is poor, therefore it is of great importance to identify novel candidate markers and potential early indicators of this disease as well as molecules that may be potential therapeutic targets. We have used a proteomic approach to identify differentially expressed proteins in peripheral cholangiocarcinoma cases and compared expression with paired non-tumoral liver tissue from the same patients. Two-dimensional fluorescence difference gel electrophoresis after labeling of the proteins with cyanines 3 and 5 was used to identify differentially expressed proteins. Overall, of the approximately 2,400 protein spots visualised in each gel, 172 protein spots showed significant differences in expression level between tumoral and non-tumoral tissue with p < 0.01. Of these, 100 spots corresponding to 138 different proteins were identified by mass spectrometry: 70 proteins were over-expressed whereas 68 proteins were under-expressed in tumoral samples compared to non-tumoral samples. Among the over-expressed proteins, immunohistochemistry studies confirmed an increased expression of 14-3-3 protein in tumoral cells while α-smooth muscle actin and periostin were shown to be overexpressed in the stromal myofibroblasts surrounding tumoral cells. α-Smooth muscle actin is a marker of myofibroblast differentiation and has been found to be a prognostic indicator in colon cancer while periostin may also have a role in cell adhesion, proliferation and migration and has been identified in other cancers. This underlines the role of stromal components in cancer progression and their interest for developing new diagnostic or therapeutic tools. STN","prediction_labels":"ANIMAL"},{"cleaned":"silencing cxcr4 inhibits tumor cell proliferation neural invasion human hilar cholangiocarcinoma background aims evaluate expression cxc motif chemokine receptor 4 cxcr4 tissues patients hilar cholangiocarcinoma hilar cca investigate cell proliferation frequency neural invasion ni influenced rnai mediated cxcr4 silencing methods immunohistochemical technique used detect expression cxcr4 41 clinical tissues including hilar cca cholangitis normal bile duct tissues effects small interference rna sirna mediated cxcr4 silencing detected hilar cca cell line qbc939 cell proliferation determined mtt expression cxcr4 monitored quantitative real time polymerase chain reaction western blot analysis ni ability hilar cca cells evaluated using perineural cell hilar cca cell coculture migration assay results expression cxcr4 significantly induced clinical hilar cca tissue positive correlation expression cxcr4 lymph node metastasis ni hilar cca patients p 0 05 silencing cxcr4 tumor cell lines sirna led significantly decreased ni p 0 05 slightly decreased cell proliferation conclusions cxcr4 likely correlated clinical recurrence hilar cca cxcr4 involved invasion proliferation human hilar cca cell line qbc939 indicating cxcr4 promising therapeutic target hilar cca stn","probabilities":0.9467213,"Title":"Silencing Of Cxcr4 Inhibits Tumor Cell Proliferation And Neural Invasion In Human Hilar Cholangiocarcinoma","Abstract":"Background/aims: To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. \r\n\r\n Methods: An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. \r\n\r\n Results: The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. \r\n\r\n Conclusions: CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA.","Source":"STN","category":"ANIMAL","training_data":"Silencing Of Cxcr4 Inhibits Tumor Cell Proliferation And Neural Invasion In Human Hilar Cholangiocarcinoma Background/aims: To evaluate the expression of CXC motif chemokine receptor 4 (CXCR4) in the tissues of patients with hilar cholangiocarcinoma (hilar-CCA) and to investigate the cell proliferation and frequency of neural invasion (NI) influenced by RNAi-mediated CXCR4 silencing. \r\n\r\n Methods: An immunohistochemical technique was used to detect the expression of CXCR4 in 41 clinical tissues, including hilar-CCA, cholangitis, and normal bile duct tissues. The effects of small interference RNA (siRNA)-mediated CXCR4 silencing were detected in the hilar-CCA cell line QBC939. Cell proliferation was determined by MTT. Expression of CXCR4 was monitored by quantitative real time polymerase chain reaction and Western blot analysis. The NI ability of hilar-CCA cells was evaluated using a perineural cell and hilar-CCA cell coculture migration assay. \r\n\r\n Results: The expression of CXCR4 was significantly induced in clinical hilar-CCA tissue. There was a positive correlation between the expression of CXCR4 and lymph node metastasis/NI in hilar-CCA patients (p<0.05). Silencing of CXCR4 in tumor cell lines by siRNA led to significantly decreased NI (p<0.05) and slightly decreased cell proliferation. \r\n\r\n Conclusions: CXCR4 is likely correlated with clinical recurrence of hilar-CCA. CXCR4 is involved in the invasion and proliferation of human hilar-CCA cell line QBC939, indicating that CXCR4 could be a promising therapeutic target for hilar-CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"staging treatment future approaches gallbladder carcinoma background gallbladder cancer common malignant cancer bile ducts third common gastrointestinal malignant world public health relatively low incidence confused symptoms result advanced disease time presentation contributing poor prognosis reduced survival associated disease main function gallbladder store excreted bile acids liver preparation meal main risk factor prolonged exposure biliary calculations although bacterial infections inflammatory conditions associated chronic inflammatory bowel conditions associated gallbladder cancer stage translates identifying residual disease reoperation incidental gallbladder cancer residual disease negatively affects survival conclusion common cancer gallbladder gallbladder cancer remains rare disease gallbladder cancer rare disease accidentally diagnosed cholecystectomy accidentally often advanced disease prognosis generally extremely poor improvements surgical resection approach re evaluated role chemotherapy radiotherapy remains controversial pubmed","probabilities":0.9799733,"Title":"Staging, Treatment, and Future Approaches of Gallbladder Carcinoma","Abstract":"BACKGROUND: Gallbladder cancer is the most common malignant cancer of the bile ducts and third most common gastrointestinal malignant in the world for public health. Its relatively low incidence and confused symptoms result in advanced disease at the time of presentation, contributing to poor prognosis and reduced survival associated with this disease. The main function of the gallbladder is to store excreted bile acids from the liver in preparation for a meal. Its main risk factor is prolonged exposure to biliary calculations, although bacterial infections and other inflammatory conditions are associated. Chronic inflammatory bowel conditions are associated with gallbladder cancer. T stage translates to identifying residual disease at reoperation for incidental gallbladder cancer and residual disease negatively affects survival. CONCLUSION: It is the most common cancer of gallbladder, gallbladder cancer remains a rare disease. Gallbladder cancer is a rare disease that can be accidentally diagnosed after cholecystectomy or accidentally, often with more advanced disease. The prognosis is generally extremely poor and improvements in surgical resection of this approach have to be re-evaluated, while the role of chemotherapy and radiotherapy remains controversial.","Source":"PubMed","category":"HUMAN","training_data":"Staging, Treatment, and Future Approaches of Gallbladder Carcinoma BACKGROUND: Gallbladder cancer is the most common malignant cancer of the bile ducts and third most common gastrointestinal malignant in the world for public health. Its relatively low incidence and confused symptoms result in advanced disease at the time of presentation, contributing to poor prognosis and reduced survival associated with this disease. The main function of the gallbladder is to store excreted bile acids from the liver in preparation for a meal. Its main risk factor is prolonged exposure to biliary calculations, although bacterial infections and other inflammatory conditions are associated. Chronic inflammatory bowel conditions are associated with gallbladder cancer. T stage translates to identifying residual disease at reoperation for incidental gallbladder cancer and residual disease negatively affects survival. CONCLUSION: It is the most common cancer of gallbladder, gallbladder cancer remains a rare disease. Gallbladder cancer is a rare disease that can be accidentally diagnosed after cholecystectomy or accidentally, often with more advanced disease. The prognosis is generally extremely poor and improvements in surgical resection of this approach have to be re-evaluated, while the role of chemotherapy and radiotherapy remains controversial. PubMed","prediction_labels":"HUMAN"},{"cleaned":"apparent diffusion coefficient potential marker tumour differentiation staging long term clinical outcomes gallbladder cancer objectives evaluate correlation tumour differentiation stage gallbladder cancer gbc apparent diffusion coefficient adc well assess whether adc value predict long term disease free survival dfs surgery methods retrospective study approved institutional review board requirement informed consent waived march 2008 june 2016 79 patients underwent magnetic resonance mr imaging diffusion weighted image subsequent surgery gbc included study correlations quantitative adc values tumour differentiation stage based american joint committee cancer ajcc assessed using spearman correlation analysis prognostic factors dfs identified multivariate cox regression analysis using imaging clinical characteristics results patients classified well n 18 moderately n 35 poorly differentiated gbcs n 26 adc value gbcs significantly correlated tumour differentiation ajcc stage p 0 001 p 0 001 respectively sixty nine patients followed 2 0 92 4 months median 23 5 months multivariate analysis significant prognostic factor dfs tumour differentiation ajcc stage binary tumour adc value hazard ratio 4 29 p 0 009 dfs rates significantly different according classification tumour adc value cut value 1 04 10 3 mm 2 p 0 004 conclusion adc value gbcs significantly correlated tumour differentiation well ajcc stage addition predicted long term outcomes surgery patients gbc key points adc values gbc tumour differentiation negatively correlated lower adc values gbc significantly correlated higher tumour stage tumour adc value useful risk stratification gbc patients pubmed","probabilities":0.9799733,"Title":"Apparent diffusion coefficient as a potential marker for tumour differentiation, staging and long-term clinical outcomes in gallbladder cancer","Abstract":"OBJECTIVES: To evaluate the correlation between tumour differentiation or stage of gallbladder cancer (GBC) and the apparent diffusion coefficient (ADC), as well as to assess whether ADC value can predict long-term disease-free survival (DFS) after surgery. METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. Between March 2008 and June 2016, 79 patients who underwent magnetic resonance (MR) imaging with diffusion-weighted image and subsequent surgery for GBC were included in this study. Correlations between quantitative ADC values and tumour differentiation or stage based on the American Joint Committee on Cancer (AJCC) were assessed using Spearman's correlation analysis. Prognostic factors for DFS were identified with multivariate Cox regression analysis using imaging and clinical characteristics. RESULTS: All patients were classified as having well- (n = 18), moderately (n = 35) or poorly differentiated GBCs (n = 26). The ADC value of GBCs was significantly correlated with tumour differentiation and AJCC stage (p < 0.001 and p < 0.001, respectively). Sixty-nine patients were followed up for 2.0-92.4 months (median, 23.5 months). On multivariate analysis, the significant prognostic factor for DFS was not tumour differentiation or AJCC stage but a binary tumour ADC value (hazard ratio, 4.29; p = 0.009). DFS rates were significantly different according to the classification of tumour ADC value (cut-off value = 1.04 × 10(-3) mm(2)/s; p = 0.004). CONCLUSION: The ADC value of GBCs was significantly correlated with tumour differentiation as well as AJCC stage. In addition, it predicted long-term outcomes after surgery in patients with GBC. KEY POINTS: • ADC values of GBC and tumour differentiation were negatively correlated. • Lower ADC values of GBC were significantly correlated with higher tumour stage. • Tumour ADC value could be useful for risk stratification of GBC patients.","Source":"PubMed","category":"HUMAN","training_data":"Apparent diffusion coefficient as a potential marker for tumour differentiation, staging and long-term clinical outcomes in gallbladder cancer OBJECTIVES: To evaluate the correlation between tumour differentiation or stage of gallbladder cancer (GBC) and the apparent diffusion coefficient (ADC), as well as to assess whether ADC value can predict long-term disease-free survival (DFS) after surgery. METHODS: This retrospective study was approved by the institutional review board and the requirement for informed consent was waived. Between March 2008 and June 2016, 79 patients who underwent magnetic resonance (MR) imaging with diffusion-weighted image and subsequent surgery for GBC were included in this study. Correlations between quantitative ADC values and tumour differentiation or stage based on the American Joint Committee on Cancer (AJCC) were assessed using Spearman's correlation analysis. Prognostic factors for DFS were identified with multivariate Cox regression analysis using imaging and clinical characteristics. RESULTS: All patients were classified as having well- (n = 18), moderately (n = 35) or poorly differentiated GBCs (n = 26). The ADC value of GBCs was significantly correlated with tumour differentiation and AJCC stage (p < 0.001 and p < 0.001, respectively). Sixty-nine patients were followed up for 2.0-92.4 months (median, 23.5 months). On multivariate analysis, the significant prognostic factor for DFS was not tumour differentiation or AJCC stage but a binary tumour ADC value (hazard ratio, 4.29; p = 0.009). DFS rates were significantly different according to the classification of tumour ADC value (cut-off value = 1.04 × 10(-3) mm(2)/s; p = 0.004). CONCLUSION: The ADC value of GBCs was significantly correlated with tumour differentiation as well as AJCC stage. In addition, it predicted long-term outcomes after surgery in patients with GBC. KEY POINTS: • ADC values of GBC and tumour differentiation were negatively correlated. • Lower ADC values of GBC were significantly correlated with higher tumour stage. • Tumour ADC value could be useful for risk stratification of GBC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"polo like kinase 2 mediator hedgehog survival signaling cholangiocarcinoma cholangiocarcinoma cca cells paradoxically express death ligand tumor necrosis factor related apoptosis inducing ligand trail thus rely potent survival signals circumvent cell death trail hedgehog hh signaling important survival pathway cca herein examine mechanisms whereby hh signaling mediates apoptosis resistance cca revealing pivotal role cell division regulating serine threonine kinase polo like kinase 2 plk2 employed 50 human cca samples 25 intrahepatic 25 extrahepatic cca well human kmch 1 mz cha 1 hucct 1 cca cells studies vivo experiments conducted using syngeneic rat orthotopic cca model human samples pololike kinase plk 1 2 3 immunoreactive cancer cells present preponderance intra extrahepatic cca specimens inhibition hh signaling cyclopamine reduced plk2 plk1 plk3 messenger rna protein expression vehicle treated sonic hh treated cca cells con rming previous microarray study plk2 regulation hh signaling appears direct hh transcription factors glioma associated oncogene 1 2 bind plk2 promotor moreover inhibition plk2 plk inhibitor bi 6727 volasertib plk2 knockdown proapoptotic cca cells bi 6727 administration plk2 knockdown decreased cellular protein levels antiapoptotic myeloid cell leukemia 1 mcl 1 effect reversed proteasome inhibitor mg 132 finally bi 6727 administration reduced mcl 1 protein expression cca cells resulting cca cell apoptosis tumor suppression vivo conclusion plk2 appears important mediator hh survival signaling results suggest plk inhibitors therapeutic value treatment human cca google scholar","probabilities":0.9467213,"Title":"Polo-Like Kinase 2 Is A Mediator Of Hedgehog Survival Signaling In Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) cells paradoxically express the death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and thus rely on potent survival signals to circumvent cell death by TRAIL. Hedgehog (Hh) signaling is an important survival pathway in CCA. Herein, we further examine the mechanisms whereby Hh signaling mediates apoptosis resistance in CCA, revealing a pivotal role for the cell division regulating serine/threonine kinase polo-like kinase 2 (PLK2). We employed 50 human CCA samples (25 intrahepatic and 25 extrahepatic CCA) as well as human KMCH-1, Mz-CHA-1, and HUCCT-1 CCA cells for these studies. In vivo experiments were conducted using a syngeneic rat orthotopic CCA model. In human samples, pololike kinase (PLK)1/2/3-immunoreactive cancer cells were present in the preponderance of intra- and extrahepatic CCA specimens. Inhibition of Hh signaling by cyclopamine reduced PLK2, but not PLK1 or PLK3, messenger RNA and protein expression in vehicle-treated and sonic Hh–treated CCA cells, confirming our previous microarray study. PLK2 regulation by Hh signaling appears to be direct, because the Hh transcription factors, glioma-associated oncogene 1 and 2, bind to the PLK2 promotor. Moreover, inhibition of PLK2 by the PLK inhibitor, BI 6727 (volasertib), or PLK2 knockdown was proapoptotic in CCA cells. BI 6727 administration or PLK2 knockdown decreased cellular protein levels of antiapoptotic myeloid cell leukemia 1 (Mcl-1), an effect reversed by the proteasome inhibitor, MG-132. Finally, BI 6727 administration reduced Mcl-1 protein expression in CCA cells, resulting in CCA cell apoptosis and tumor suppression in vivo. Conclusion: PLK2 appears to be an important mediator of Hh survival signaling. These results suggest PLK inhibitors to be of therapeutic value for treatment of human CCA","Source":"Google Scholar","category":"ANIMAL","training_data":"Polo-Like Kinase 2 Is A Mediator Of Hedgehog Survival Signaling In Cholangiocarcinoma Cholangiocarcinoma (CCA) cells paradoxically express the death ligand tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and thus rely on potent survival signals to circumvent cell death by TRAIL. Hedgehog (Hh) signaling is an important survival pathway in CCA. Herein, we further examine the mechanisms whereby Hh signaling mediates apoptosis resistance in CCA, revealing a pivotal role for the cell division regulating serine/threonine kinase polo-like kinase 2 (PLK2). We employed 50 human CCA samples (25 intrahepatic and 25 extrahepatic CCA) as well as human KMCH-1, Mz-CHA-1, and HUCCT-1 CCA cells for these studies. In vivo experiments were conducted using a syngeneic rat orthotopic CCA model. In human samples, pololike kinase (PLK)1/2/3-immunoreactive cancer cells were present in the preponderance of intra- and extrahepatic CCA specimens. Inhibition of Hh signaling by cyclopamine reduced PLK2, but not PLK1 or PLK3, messenger RNA and protein expression in vehicle-treated and sonic Hh–treated CCA cells, confirming our previous microarray study. PLK2 regulation by Hh signaling appears to be direct, because the Hh transcription factors, glioma-associated oncogene 1 and 2, bind to the PLK2 promotor. Moreover, inhibition of PLK2 by the PLK inhibitor, BI 6727 (volasertib), or PLK2 knockdown was proapoptotic in CCA cells. BI 6727 administration or PLK2 knockdown decreased cellular protein levels of antiapoptotic myeloid cell leukemia 1 (Mcl-1), an effect reversed by the proteasome inhibitor, MG-132. Finally, BI 6727 administration reduced Mcl-1 protein expression in CCA cells, resulting in CCA cell apoptosis and tumor suppression in vivo. Conclusion: PLK2 appears to be an important mediator of Hh survival signaling. These results suggest PLK inhibitors to be of therapeutic value for treatment of human CCA Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"clinicopathological features prognostic factors young patients surgically treated liver cancer article compares clinical characteristics prognosis young patients different age groups liver cancer lc retrospective study searched surveillance epidemiology end results population based database identified 2641 patients diagnosed lc 1988 2005 patients categorized 2 different age ranges group 1 35 years group 2 36 45 years five year cancer specific survival css data obtained kaplan meier methods multivariable cox regression models used analyze long term survival outcomes risk factors significant differences age groups stage tumor size p 0 001 5 year liver css rate 20 4 14 5 respectively p 0 001 univariate multivariate analysis also confirmed difference p 0 001 analysis showed significant difference existed localized regional distant stage patients young patients lc age 18 45 years inherently heterogeneous patients aged 35 years better css aged 36 45 years despite exhibiting unfavorable clinicopathological characteristics pubmed","probabilities":0.9799733,"Title":"Clinicopathological features and prognostic factors of young patients with surgically treated liver cancer","Abstract":"This article compares the clinical characteristics and prognosis of young patients in different age groups with liver cancer (LC). In this retrospective study, we searched the Surveillance, Epidemiology, and End Results population-based database and identified 2641 patients who had been diagnosed with LC between 1988 and 2005. These patients were categorized into 2 different age ranges: Group 1 (≤35 years) and Group 2 (36-45 years). Five-year cancer-specific survival (CSS) data were obtained. Kaplan-Meier methods and multivariable Cox regression models were used to analyze the long-term survival outcomes and risk factors. There were significant differences between the age groups for stage and tumor size (P < 0.001). The 5-year liver CSS rate was 20.4% and 14.5%, respectively (P < 0.001). Univariate and multivariate analysis also confirmed the difference (P < 0.001). Further analysis showed that this significant difference existed in localized, regional, and distant-stage patients. Young patients with LC of age 18 to 45 years are inherently heterogeneous. Patients aged ≤35 years have better CSS than those aged 36 to 45 years, despite exhibiting unfavorable clinicopathological characteristics.","Source":"PubMed","category":"HUMAN","training_data":"Clinicopathological features and prognostic factors of young patients with surgically treated liver cancer This article compares the clinical characteristics and prognosis of young patients in different age groups with liver cancer (LC). In this retrospective study, we searched the Surveillance, Epidemiology, and End Results population-based database and identified 2641 patients who had been diagnosed with LC between 1988 and 2005. These patients were categorized into 2 different age ranges: Group 1 (≤35 years) and Group 2 (36-45 years). Five-year cancer-specific survival (CSS) data were obtained. Kaplan-Meier methods and multivariable Cox regression models were used to analyze the long-term survival outcomes and risk factors. There were significant differences between the age groups for stage and tumor size (P < 0.001). The 5-year liver CSS rate was 20.4% and 14.5%, respectively (P < 0.001). Univariate and multivariate analysis also confirmed the difference (P < 0.001). Further analysis showed that this significant difference existed in localized, regional, and distant-stage patients. Young patients with LC of age 18 to 45 years are inherently heterogeneous. Patients aged ≤35 years have better CSS than those aged 36 to 45 years, despite exhibiting unfavorable clinicopathological characteristics. PubMed","prediction_labels":"HUMAN"},{"cleaned":"hepatopancreatoduodenectomy controversial treatment bile duct gallbladder cancer european perspective background hepatopancreatoduodenectomy hpd aggressive operation treatment advanced bile duct gallbladder cancer associated high perioperative morbidity mortality uncertain oncological benefit terms survival reports hpd western centers exist purpose study evaluate safety efficacy hpd european centers method members european african hepatopancreatobiliary association invited report consecutive patients operated hpd bile duct gallbladder cancer january 2003 january 2018 patient tumor characteristics perioperative survival outcomes analyzed results total 66 patients 19 european centers included analysis 90 day mortality rate 17 13 bile duct gallbladder cancer respectively factors predictive perioperative mortality patient disease specific three year overall survival excluding 90 day mortality 80 bile duct 30 gallbladder cancer p 0 013 multivariable analysis r0 resection significant impact overall survival conclusion hpd although associated substantial perioperative mortality offer survival benefit patient subgroups bile duct cancer gallbladder cancer achieve negative resection margins paramount improved survival outcome stn","probabilities":0.9799733,"Title":"Hepatopancreatoduodenectomy -A Controversial Treatment For Bile Duct And Gallbladder Cancer From A European Perspective","Abstract":"Background: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. \r\n\r\n Method: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. \r\n\r\n Results: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. \r\n\r\n Conclusion: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome.","Source":"STN","category":"HUMAN","training_data":"Hepatopancreatoduodenectomy -A Controversial Treatment For Bile Duct And Gallbladder Cancer From A European Perspective Background: Hepatopancreatoduodenectomy (HPD) is an aggressive operation for treatment of advanced bile duct and gallbladder cancer associated with high perioperative morbidity and mortality, and uncertain oncological benefit in terms of survival. Few reports on HPD from Western centers exist. The purpose of this study was to evaluate safety and efficacy for HPD in European centers. \r\n\r\n Method: Members of the European-African HepatoPancreatoBiliary Association were invited to report all consecutive patients operated with HPD for bile duct or gallbladder cancer between January 2003 and January 2018. The patient and tumor characteristics, perioperative and survival outcomes were analyzed. \r\n\r\n Results: In total, 66 patients from 19 European centers were included in the analysis. 90-day mortality rate was 17% and 13% for bile duct and gallbladder cancer respectively. All factors predictive of perioperative mortality were patient and disease-specific. The three-year overall survival excluding 90-day mortality was 80% for bile duct and 30% for gallbladder cancer (P = 0.013). In multivariable analysis R0-resection had a significant impact on overall survival. \r\n\r\n Conclusion: HPD, although being associated with substantial perioperative mortality, can offer a survival benefit in patient subgroups with bile duct cancer and gallbladder cancer. To achieve negative resection margins is paramount for an improved survival outcome. STN","prediction_labels":"HUMAN"},{"cleaned":"role stromal derived factor 1 sdf 1 cxcr4 axis interaction hepatic stellate cells cholangiocarcinoma backgrounds aims cholangiocarcinoma cca highly fatal early invasion widespread metastasis lack effective therapy migration invasion metastasis cca cells modulated signals received stromal cells sdf 1 cxcr4 axis emerges pivotal regulator migration survival different tumor cells aim present study characterize interaction cca cells human hepatic stellate cells hhsc focusing role sdf 1 methods intrahepatic cca cell line hucct 1 primary hhsc used study rna expression examined rtq pcr protein expression western blotting immunofluorescence microscopy immunohistochemistry also employed migration cca cells assessed using modified boyden chambers results cxcr4 clearly expressed cca cells human cca liver specimens sdf 1 hhsc conditioned medium cm promoted hucct 1 cell migration abrogated pre incubation amd3100 non peptide antagonist cxcr4 receptor addition hucct 1 cells silenced cxcr4 migrate presence sdf 1 p erk p akt implicated hucct 1 migration showed biphasic trend stimulation sdf 1 finally sdf 1 induced apoptotic rescue hucct 1 cells binding cxcr4 conclusions study demonstrates cca cells migration survival modulated crosstalk sdf 1 released hhsc hucct 1 cells bearing cxcr4 stn","probabilities":0.9467213,"Title":"Role Of The Stromal-Derived Factor-1 (Sdf-1)-Cxcr4 Axis In The Interaction Between Hepatic Stellate Cells And Cholangiocarcinoma","Abstract":"Backgrounds & aims: Cholangiocarcinoma (CCA) is highly fatal because of early invasion, widespread metastasis, and lack of an effective therapy. Migration, invasion, and metastasis of CCA cells are modulated by signals received from stromal cells. The SDF-1-CXCR4 axis emerges as a pivotal regulator of migration and survival of different tumor cells. The aim of the present study was to characterize the interaction between CCA cells and human hepatic stellate cells (hHSC) focusing on the role of SDF-1. \r\n\r\n Methods: The intrahepatic CCA cell line HuCCT-1 and primary hHSC were used for this study. RNA expression was examined by RTQ-PCR and protein expression by Western blotting. Immunofluorescence microscopy and immunohistochemistry were also employed. Migration of CCA cells was assessed using modified Boyden chambers. \r\n\r\n Results: CXCR4 was clearly expressed in CCA cells of human CCA liver specimens. SDF-1 and hHSC conditioned medium (CM) promoted HuCCT-1 cell migration, which was abrogated by pre-incubation with AMD3100, a non-peptide antagonist of the CXCR4 receptor. In addition, HuCCT-1 cells silenced for CXCR4 did not migrate in presence of SDF-1. Both P-ERK and p-AKT were implicated in HuCCT-1 migration and showed a biphasic trend under stimulation of SDF-1. Finally, SDF-1 induced apoptotic rescue of HuCCT-1 cells by binding to CXCR4. \r\n\r\n Conclusions: Our study demonstrates that CCA cells migration and survival are modulated by the crosstalk between SDF-1, released by hHSC, and HuCCT-1 cells bearing CXCR4.","Source":"STN","category":"ANIMAL","training_data":"Role Of The Stromal-Derived Factor-1 (Sdf-1)-Cxcr4 Axis In The Interaction Between Hepatic Stellate Cells And Cholangiocarcinoma Backgrounds & aims: Cholangiocarcinoma (CCA) is highly fatal because of early invasion, widespread metastasis, and lack of an effective therapy. Migration, invasion, and metastasis of CCA cells are modulated by signals received from stromal cells. The SDF-1-CXCR4 axis emerges as a pivotal regulator of migration and survival of different tumor cells. The aim of the present study was to characterize the interaction between CCA cells and human hepatic stellate cells (hHSC) focusing on the role of SDF-1. \r\n\r\n Methods: The intrahepatic CCA cell line HuCCT-1 and primary hHSC were used for this study. RNA expression was examined by RTQ-PCR and protein expression by Western blotting. Immunofluorescence microscopy and immunohistochemistry were also employed. Migration of CCA cells was assessed using modified Boyden chambers. \r\n\r\n Results: CXCR4 was clearly expressed in CCA cells of human CCA liver specimens. SDF-1 and hHSC conditioned medium (CM) promoted HuCCT-1 cell migration, which was abrogated by pre-incubation with AMD3100, a non-peptide antagonist of the CXCR4 receptor. In addition, HuCCT-1 cells silenced for CXCR4 did not migrate in presence of SDF-1. Both P-ERK and p-AKT were implicated in HuCCT-1 migration and showed a biphasic trend under stimulation of SDF-1. Finally, SDF-1 induced apoptotic rescue of HuCCT-1 cells by binding to CXCR4. \r\n\r\n Conclusions: Our study demonstrates that CCA cells migration and survival are modulated by the crosstalk between SDF-1, released by hHSC, and HuCCT-1 cells bearing CXCR4. STN","prediction_labels":"ANIMAL"},{"cleaned":"efficacy safety gemcitabine monotherapy patients advanced biliary tract cancer objective aim study analyze efficacy feasibility gemcitabine monotherapy patients unresectable advanced recurrent biliary tract cancer btc methods six patients unresectable advanced btc 12 patients recurrent btc received gemcitabine monotherapy gemcitabine 800 1 000mg m2 administered intravenously 30 minutes days 1 8 15 every 28 days disease toxicity assessed week patients completion gemcitabine treatment computed tomographic magnetic resonance imaging studies done every 8 weeks chemotherapy every 4 weeks progressive disease suspected tumor response determined according response evaluation criteria solid tumors toxicity assessed using national cancer institute common toxicity criteria version 2 0 time progression survival time also calculated results patients unresectable btc overall response rate median time progression patients partial response stable disease 66 7 5 68 months respectively clinical benefit observed 3 patients stable disease 50 median survival time 5 2 months patients recurrent btc 4 patients 33 obtained partial responses 2 patients 17 stable disease median time progression 8 2 months six 12 patients 50 obtained clinical benefit median survival time cancer intrahepatic bile duct extrahepatic bile duct ampulla vater 2 8 months 8 5 months 10 7 months respectively significant correlation survival time resectability initial procedure r number detected survival time patients performance status 0 1 significantly longer patients performance status 2 p 0 0051 neither grade 3 4 hematologic toxicity grade 3 4 nonhematologic toxicity observed treatment related deaths observed conclusion gemcitabine monotherapy may provide favorable prognosis patients advanced btc best supportive care alone moreover regimen may represent therapeutic option adjuvant setting patients btc google scholar","probabilities":0.9799733,"Title":"Efficacy And Safety Of Gemcitabine Monotherapy For Patients With Advanced Biliary Tract Cancer","Abstract":"Objective: The aim of this study was to analyze the efficacy and feasibility of gemcitabine monotherapy in patients with unresectable advanced or recurrent biliary tract cancer (BTC). Methods: Six patients with unresectable advanced BTC and 12 patients with recurrent BTC received gemcitabine monotherapy. Gemcitabine (800―1,000mg\u0002 m2) was administered intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Disease and toxicity were assessed once a week in all patients until the completion of gemcitabine treatment. Computed tomographic\u0002magnetic resonance imaging studies were done every 8 weeks during chemotherapy, and every 4 weeks if progressive disease was suspected. Tumor response was determined according to the Response Evaluation Criteria in Solid Tumors. Toxicity was assessed using the National Cancer Institute Common Toxicity Criteria version 2.0. The time to progression and survival time were also calculated. Results: In patients with unresectable BTC, the overall response rate and the median time to progression for patients with partial response or stable disease was 66.7% and 5.68 months, respectively. Clinical benefit was observed in 3 patients with stable disease (50%). The median survival time was 5.2 months. In patients with recurrent BTC, 4 patients (33%) obtained partial responses and 2 patients (17%) had stable disease. The median time to progression was 8.2 months. Six of 12 patients (50%) obtained clinical benefit. The median survival time for cancer of the intrahepatic bile duct, the extrahepatic bile duct, and the ampulla of Vater were 2.8 months, 8.5 months, and 10.7 months, respectively. No significant correlation between the survival time and the resectability of the initial procedure (R number) was detected. The survival time for patients with a performance status of 0 or 1 was significantly longer than that for patients with a performance status of 2 (P=0.0051). Neither grade 3\u00024 hematologic toxicity nor grade 3\u00024 nonhematologic toxicity was observed. No treatment-related deaths were observed. Conclusion: Gemcitabine monotherapy may provide a more favorable prognosis in patients with advanced BTC than does best supportive care alone. Moreover, this regimen may represent a therapeutic option for the adjuvant setting in patients with BTC.","Source":"Google Scholar","category":"HUMAN","training_data":"Efficacy And Safety Of Gemcitabine Monotherapy For Patients With Advanced Biliary Tract Cancer Objective: The aim of this study was to analyze the efficacy and feasibility of gemcitabine monotherapy in patients with unresectable advanced or recurrent biliary tract cancer (BTC). Methods: Six patients with unresectable advanced BTC and 12 patients with recurrent BTC received gemcitabine monotherapy. Gemcitabine (800―1,000mg\u0002 m2) was administered intravenously over 30 minutes on days 1, 8, and 15 every 28 days. Disease and toxicity were assessed once a week in all patients until the completion of gemcitabine treatment. Computed tomographic\u0002magnetic resonance imaging studies were done every 8 weeks during chemotherapy, and every 4 weeks if progressive disease was suspected. Tumor response was determined according to the Response Evaluation Criteria in Solid Tumors. Toxicity was assessed using the National Cancer Institute Common Toxicity Criteria version 2.0. The time to progression and survival time were also calculated. Results: In patients with unresectable BTC, the overall response rate and the median time to progression for patients with partial response or stable disease was 66.7% and 5.68 months, respectively. Clinical benefit was observed in 3 patients with stable disease (50%). The median survival time was 5.2 months. In patients with recurrent BTC, 4 patients (33%) obtained partial responses and 2 patients (17%) had stable disease. The median time to progression was 8.2 months. Six of 12 patients (50%) obtained clinical benefit. The median survival time for cancer of the intrahepatic bile duct, the extrahepatic bile duct, and the ampulla of Vater were 2.8 months, 8.5 months, and 10.7 months, respectively. No significant correlation between the survival time and the resectability of the initial procedure (R number) was detected. The survival time for patients with a performance status of 0 or 1 was significantly longer than that for patients with a performance status of 2 (P=0.0051). Neither grade 3\u00024 hematologic toxicity nor grade 3\u00024 nonhematologic toxicity was observed. No treatment-related deaths were observed. Conclusion: Gemcitabine monotherapy may provide a more favorable prognosis in patients with advanced BTC than does best supportive care alone. Moreover, this regimen may represent a therapeutic option for the adjuvant setting in patients with BTC. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"igfbp7 associated prognosis suppress cell survival cholangiocarcinoma insulin like growth factor binding protein 7 igfbp7 secreted protein expression restrained varied solid tumours report biological role igfbp7 cholangiocarcinoma cca found high expression igfbp7 correlated better overall survival cca patients investigate hypothetic antineoplastic activity igfbp7 cca induced overexpression igfbp7 qbc939 rbe cells well knockdown hccc9810 cells biological functions triggered level changes igfbp7 assessed including proliferation cell cycle distribution apoptosis invasion evaluation cell growth assessment showed enhanced igfbp7 expression significantly retarded proliferation rates qbc939 rbe cells enhancement observed igfbp7 inhibited hccc9810 cells inhibition cell viability induced via g2 m phase arrest apoptosis qbc939 rbe cells possess highly invasive ability igfbp7 overexpression attenuated serious invasiveness reversing mesenchymal phenotype endothelial signature next investigated potential mechanism involving igfbp7 induced tumour suppression found increased expression igfbp7 resulted decrease igf ir irs 1 phosphor akt protein levels accompanied elevation phorsphor p38mapk results suggest igfbp7 might related cca carcinogenesis metastasis implicates igfbp7 might become prospective benchmark cca diagnosis therapy stn","probabilities":0.9467213,"Title":"Igfbp7 Is Associated To Prognosis And Could Suppress Cell Survival In Cholangiocarcinoma","Abstract":"Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein and its expression was restrained in varied solid tumours, but there was no report about biological role of IGFBP7 in cholangiocarcinoma (CCA). Here, we found that high expression of IGFBP7 correlated to a better overall survival in CCA patients. To investigate the hypothetic antineoplastic activity of IGFBP7 in CCA, we induced overexpression of IGFBP7 in QBC939 and RBE cells, as well as knockdown in HCCC9810 cells. And the biological functions triggered by level changes of IGFBP7 were assessed, including proliferation, cell cycle distribution, apoptosis and invasion evaluation. Cell growth assessment showed that enhanced IGFBP7 expression significantly retarded proliferation rates of QBC939 and RBE cells while an enhancement was observed in IGFBP7-inhibited HCCC9810 cells. The inhibition of cell viability was induced via G2/M phase arrest and apoptosis. Both QBC939 and RBE cells possess highly invasive ability, and IGFBP7 overexpression attenuated their serious invasiveness by reversing their mesenchymal phenotype to endothelial signature. We next investigated the potential mechanism involving in IGFBP7-induced tumour suppression and found that increased expression of IGFBP7 resulted in decrease of IGF-IR, IRS-1 and phosphor-AKT protein levels, accompanied with elevation of phorsphor-p38MAPK. These results suggest that IGFBP7 might be related to CCA carcinogenesis and metastasis, which further implicates that IGFBP7 might become a prospective benchmark for CCA diagnosis and therapy.","Source":"STN","category":"ANIMAL","training_data":"Igfbp7 Is Associated To Prognosis And Could Suppress Cell Survival In Cholangiocarcinoma Insulin-like growth factor-binding protein 7 (IGFBP7) is a secreted protein and its expression was restrained in varied solid tumours, but there was no report about biological role of IGFBP7 in cholangiocarcinoma (CCA). Here, we found that high expression of IGFBP7 correlated to a better overall survival in CCA patients. To investigate the hypothetic antineoplastic activity of IGFBP7 in CCA, we induced overexpression of IGFBP7 in QBC939 and RBE cells, as well as knockdown in HCCC9810 cells. And the biological functions triggered by level changes of IGFBP7 were assessed, including proliferation, cell cycle distribution, apoptosis and invasion evaluation. Cell growth assessment showed that enhanced IGFBP7 expression significantly retarded proliferation rates of QBC939 and RBE cells while an enhancement was observed in IGFBP7-inhibited HCCC9810 cells. The inhibition of cell viability was induced via G2/M phase arrest and apoptosis. Both QBC939 and RBE cells possess highly invasive ability, and IGFBP7 overexpression attenuated their serious invasiveness by reversing their mesenchymal phenotype to endothelial signature. We next investigated the potential mechanism involving in IGFBP7-induced tumour suppression and found that increased expression of IGFBP7 resulted in decrease of IGF-IR, IRS-1 and phosphor-AKT protein levels, accompanied with elevation of phorsphor-p38MAPK. These results suggest that IGFBP7 might be related to CCA carcinogenesis and metastasis, which further implicates that IGFBP7 might become a prospective benchmark for CCA diagnosis and therapy. STN","prediction_labels":"ANIMAL"},{"cleaned":"laparoscopic cholecystectomy patients history gastrectomy background objectives patients previous gastrectomy increased incidence gallstones gallbladder morbidity requiring surgery investigated possible risk factors contribute severe gallbladder disease patients previous gastrectomy role laparoscopic cholecystectomy lc treatment patients methods retrospective study reviewed database patients underwent lc hospital period january 1 2010 may 1 2015 results average operation time patients previous gastrectomy longer p 05 operation times patients long interval 5 years gastrectomy lc showed statistical difference patients without history gastrectomy p 05 conversion rate differ 2 groups p 05 patients previous gastrectomy conversion rate significantly reduced adopted comprehensive preoperative evaluation procedure p 05 frequency cholecystitis attacks rate combination gallbladder polyps rate combination pancreatitis higher gallstone formation time shorter patients malignant tumor undergoing billroth ii gastroenterostomy esophagojejunostomy accompanying diabetes mellitus hypercholesterolemia p 05 conclusion lc plays important role treatment benign gallbladder diseases patients history gastrectomy comprehensive preoperative evaluation accomplished surgical technique necessary successful outcomes previously identified clinical features may represent risk factor severe cholecystic morbidity patients pubmed","probabilities":0.9799733,"Title":"Laparoscopic Cholecystectomy in Patients With History of Gastrectomy","Abstract":"BACKGROUND AND OBJECTIVES: Patients with previous gastrectomy have an increased incidence of gallstones and gallbladder morbidity requiring surgery. We investigated the possible risk factors that contribute to severe gallbladder disease in patients with previous gastrectomy and the role of laparoscopic cholecystectomy (LC) in the treatment of these patients. METHODS: In this retrospective study, we reviewed a database of patients who underwent LC in our hospital during the period January 1, 2010, through May 1, 2015. RESULTS: The average operation time in patients with previous gastrectomy was longer (P < .05), but the operation times of patients with a long interval (>5 years) between gastrectomy and LC showed no statistical difference from those of patients without a history of gastrectomy (P > .05). The conversion rate did not differ between the 2 groups (P > .05), but in patients with previous gastrectomy, the conversion rate was significantly reduced after we adopted a comprehensive preoperative evaluation procedure (P < .05). The frequency of cholecystitis attacks, rate of combination with gallbladder polyps, and rate of combination with pancreatitis were higher and gallstone formation time shorter, in the patients with malignant tumor, those undergoing Billroth II gastroenterostomy or esophagojejunostomy, and those with accompanying diabetes mellitus or hypercholesterolemia (P < .05). CONCLUSION: LC plays an important role in the treatment of benign gallbladder diseases in patients with a history of gastrectomy, and a comprehensive preoperative evaluation and accomplished surgical technique are necessary for successful outcomes. Previously identified clinical features may represent a risk factor for severe cholecystic morbidity in these patients.","Source":"PubMed","category":"HUMAN","training_data":"Laparoscopic Cholecystectomy in Patients With History of Gastrectomy BACKGROUND AND OBJECTIVES: Patients with previous gastrectomy have an increased incidence of gallstones and gallbladder morbidity requiring surgery. We investigated the possible risk factors that contribute to severe gallbladder disease in patients with previous gastrectomy and the role of laparoscopic cholecystectomy (LC) in the treatment of these patients. METHODS: In this retrospective study, we reviewed a database of patients who underwent LC in our hospital during the period January 1, 2010, through May 1, 2015. RESULTS: The average operation time in patients with previous gastrectomy was longer (P < .05), but the operation times of patients with a long interval (>5 years) between gastrectomy and LC showed no statistical difference from those of patients without a history of gastrectomy (P > .05). The conversion rate did not differ between the 2 groups (P > .05), but in patients with previous gastrectomy, the conversion rate was significantly reduced after we adopted a comprehensive preoperative evaluation procedure (P < .05). The frequency of cholecystitis attacks, rate of combination with gallbladder polyps, and rate of combination with pancreatitis were higher and gallstone formation time shorter, in the patients with malignant tumor, those undergoing Billroth II gastroenterostomy or esophagojejunostomy, and those with accompanying diabetes mellitus or hypercholesterolemia (P < .05). CONCLUSION: LC plays an important role in the treatment of benign gallbladder diseases in patients with a history of gastrectomy, and a comprehensive preoperative evaluation and accomplished surgical technique are necessary for successful outcomes. Previously identified clinical features may represent a risk factor for severe cholecystic morbidity in these patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"surgical outcomes 131 cases carcinosarcoma hepatobiliary tract carcinosarcoma hepatobiliary tract highly aggressive poor prognosis even curative resection purpose study collate analyze published data clarify surgical outcome carcinosarcoma hepatobiliary tract relationships potential prognostic factors survival surgery surveyed worldwide literature 1970 2012 obtained clinicopathological data 131 patients undergone surgical resection carcinosarcoma hepatobiliary tract including one patient clinic relationships potential prognostic factors survival rates examined using kaplan meier method log rank test overall 1 3 5 year survival rates patients carcinosarcoma hepatobiliary tract surgery 44 0 29 3 27 0 respectively univariate analyses age gender significant prognostic factors however advanced stage according classification union international cancer control resected specimens significantly associated shorter survival time surgery although carcinosarcoma hepatobiliary tract remains rare disease worldwide poor prognosis even curative resection demands epidemiological pathological study lead development new management strategies pubmed","probabilities":0.9799733,"Title":"Surgical outcomes for 131 cases of carcinosarcoma of the hepatobiliary tract","Abstract":"Carcinosarcoma of the hepatobiliary tract is highly aggressive and has a poor prognosis even after curative resection. The purpose of this study was to collate and analyze published data to clarify the surgical outcome of carcinosarcoma of the hepatobiliary tract and the relationships between potential prognostic factors and survival after surgery. We surveyed worldwide literature from 1970 to 2012 and obtained clinicopathological data for 131 patients who had undergone surgical resection for carcinosarcoma of the hepatobiliary tract, including one patient from our clinic. The relationships between potential prognostic factors and survival rates were examined using the Kaplan-Meier method and the log-rank test. The overall 1-, 3-, and 5-year survival rates for patients with carcinosarcoma of the hepatobiliary tract after surgery were 44.0, 29.3, and 27.0 %, respectively. In univariate analyses, age and gender were not significant prognostic factors; however, advanced stage according to the classification of the Union for International Cancer Control in resected specimens was significantly associated with a shorter survival time after surgery. Although carcinosarcoma of the hepatobiliary tract remains a rare disease worldwide, its poor prognosis, even after curative resection, demands further epidemiological and pathological study that could lead to the development of new management strategies.","Source":"PubMed","category":"HUMAN","training_data":"Surgical outcomes for 131 cases of carcinosarcoma of the hepatobiliary tract Carcinosarcoma of the hepatobiliary tract is highly aggressive and has a poor prognosis even after curative resection. The purpose of this study was to collate and analyze published data to clarify the surgical outcome of carcinosarcoma of the hepatobiliary tract and the relationships between potential prognostic factors and survival after surgery. We surveyed worldwide literature from 1970 to 2012 and obtained clinicopathological data for 131 patients who had undergone surgical resection for carcinosarcoma of the hepatobiliary tract, including one patient from our clinic. The relationships between potential prognostic factors and survival rates were examined using the Kaplan-Meier method and the log-rank test. The overall 1-, 3-, and 5-year survival rates for patients with carcinosarcoma of the hepatobiliary tract after surgery were 44.0, 29.3, and 27.0 %, respectively. In univariate analyses, age and gender were not significant prognostic factors; however, advanced stage according to the classification of the Union for International Cancer Control in resected specimens was significantly associated with a shorter survival time after surgery. Although carcinosarcoma of the hepatobiliary tract remains a rare disease worldwide, its poor prognosis, even after curative resection, demands further epidemiological and pathological study that could lead to the development of new management strategies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"optimum palliation inoperable hilar cholangiocarcinoma comparative assessment efficacy plastic self expanding metal stents background endoscopic retrograde biliary drainage erbd plastic self expanding metal stents sems often performed palliative care cholangiocarcinoma objective objective compare clinical effectiveness including stent patency complication rate need salvage percutaneous transhepatic biliary drainage sems plastic stents methods total 100 patients inoperable cholangiocarcinoma identified endoscopic database 1 1 01 9 30 06 tertiary cancer hospital clinical history retrospectively reviewed patients followed death re intervention least one year stent patency patient survival estimated kaplan meier analysis supplemented log rank test comparisons groups results forty eight patients sems placed 52 patients plastic stents placed erbd successful 46 95 8 sems group 49 94 2 plastic group p 0 67 median patency times 1 86 months plastic group 5 56 months sems group p 0 0001 mean 1 53 4 60 re interventions performed sems plastic groups respectively p 0 05 complications occurred 4 48 8 3 sems group 4 52 7 7 plastic group p 0 79 median survival 9 08 8 22 months sems plastic stent groups respectively p 0 50 conclusion metallic stent patency superior plastic stents bismuth corlette classifications hilar cholangiocarcinoma similar complication rates sems seem cost effective feasible considered initial intervention patients inoperable hilar cholangiocarcinoma pubmed","probabilities":0.9799733,"Title":"Optimum palliation of inoperable hilar cholangiocarcinoma: comparative assessment of the efficacy of plastic and self-expanding metal stents","Abstract":"BACKGROUND: Endoscopic retrograde biliary drainage (ERBD) with plastic or self-expanding metal stents (SEMS) is often performed for palliative care for cholangiocarcinoma. OBJECTIVE: The objective was to compare the clinical effectiveness, including stent patency, complication rate, and need for salvage percutaneous transhepatic biliary drainage, of SEMS and plastic stents. METHODS: A total of 100 patients with inoperable cholangiocarcinoma were identified from an endoscopic database from 1/1/01 to 9/30/06 at a tertiary cancer hospital and their clinical history was retrospectively reviewed. All patients were followed to death, re-intervention, or for at least one year. Stent patency and patient survival were estimated by Kaplan-Meier analysis, supplemented by the log-rank test for comparisons between groups. RESULTS: Forty-eight patients had SEMS placed and 52 patients had plastic stents placed. ERBD was successful in 46 (95.8%) in the SEMS group and 49 (94.2%) in the plastic group (P = 0.67). Median patency times were 1.86 months in the plastic group and 5.56 months in the SEMS group (P < 0.0001). A mean of 1.53 and 4.60 re-interventions were performed in the SEMS and plastic groups, respectively (P < 0.05). Complications occurred in 4/48 (8.3%) in the SEMS group and 4/52 (7.7%) in the plastic group (P = 0.79). Median survival was 9.08 and 8.22 months in the SEMS and plastic stent groups, respectively (P = 0.50). CONCLUSION: Metallic stent patency was superior to that of plastic stents in all Bismuth-Corlette classifications of hilar cholangiocarcinoma with similar complication rates. SEMS seem to be cost-effective and, when feasible, should be considered as an initial intervention in patients with inoperable hilar cholangiocarcinoma.","Source":"PubMed","category":"HUMAN","training_data":"Optimum palliation of inoperable hilar cholangiocarcinoma: comparative assessment of the efficacy of plastic and self-expanding metal stents BACKGROUND: Endoscopic retrograde biliary drainage (ERBD) with plastic or self-expanding metal stents (SEMS) is often performed for palliative care for cholangiocarcinoma. OBJECTIVE: The objective was to compare the clinical effectiveness, including stent patency, complication rate, and need for salvage percutaneous transhepatic biliary drainage, of SEMS and plastic stents. METHODS: A total of 100 patients with inoperable cholangiocarcinoma were identified from an endoscopic database from 1/1/01 to 9/30/06 at a tertiary cancer hospital and their clinical history was retrospectively reviewed. All patients were followed to death, re-intervention, or for at least one year. Stent patency and patient survival were estimated by Kaplan-Meier analysis, supplemented by the log-rank test for comparisons between groups. RESULTS: Forty-eight patients had SEMS placed and 52 patients had plastic stents placed. ERBD was successful in 46 (95.8%) in the SEMS group and 49 (94.2%) in the plastic group (P = 0.67). Median patency times were 1.86 months in the plastic group and 5.56 months in the SEMS group (P < 0.0001). A mean of 1.53 and 4.60 re-interventions were performed in the SEMS and plastic groups, respectively (P < 0.05). Complications occurred in 4/48 (8.3%) in the SEMS group and 4/52 (7.7%) in the plastic group (P = 0.79). Median survival was 9.08 and 8.22 months in the SEMS and plastic stent groups, respectively (P = 0.50). CONCLUSION: Metallic stent patency was superior to that of plastic stents in all Bismuth-Corlette classifications of hilar cholangiocarcinoma with similar complication rates. SEMS seem to be cost-effective and, when feasible, should be considered as an initial intervention in patients with inoperable hilar cholangiocarcinoma. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic significance neutrophil lymphocyte ratio patients gallbladder carcinoma background numerous literature suggest preoperative neutrophil lymphocyte ratio nlr correlated prognosis various cancers however prognostic significance nlr gallbladder carcinoma gbc remains determined methods data 316 gbc patients surgical treatment reviewed retrospectively receiver operating characteristic roc curve performed determine optimal cut value nlr kaplan meier method cox regression proportional hazard model performed evaluate prognostic factors results optimal cut point nlr 2 61 according roc curve according univariable analysis nlr differentiation tnm stage associated gbc prognosis gbc patients nlr 2 61 worsened 5 year overall survival os compared patients nlr 2 61 p 0 001 multiple analyses indicated nlr hazard ratio hr 1 65 95 percent confidence interval 95 ci 1 25 2 17 differentiation hr 1 25 95 ci 0 97 1 62 tnm stage hr 3 79 95 ci 2 09 6 87 independent prognostic factors gbc gbc patients stage iii iv nlr 2 61 exhibited worse os compared patients nlr 2 61 p 0 05 prognostic evaluation model based independent prognostic factors established conclusion nlr associated gbc prognosis potential prognostic marker gbc preoperatively also postoperatively pubmed","probabilities":0.9799733,"Title":"Prognostic significance of neutrophil to lymphocyte ratio in patients with gallbladder carcinoma","Abstract":"BACKGROUND: Numerous literature suggest that the preoperative neutrophil to lymphocyte ratio (NLR) is correlated to the prognosis of various cancers. However, the prognostic significance of NLR in gallbladder carcinoma (GBC) remains to be determined. METHODS: Data from 316 GBC patients with surgical treatment were reviewed retrospectively. A receiver operating characteristic (ROC) curve was performed to determine an optimal cut-off value for NLR. The Kaplan-Meier method and Cox regression proportional hazard model were performed to evaluate prognostic factors. RESULTS: The optimal cut-off point for NLR was 2.61 according to the ROC curve. According to the univariable analysis, NLR, differentiation and TNM stage were associated with GBC prognosis. GBC patients with NLR > 2.61 have worsened 5-year overall survival (OS) compared to patients with NLR ≤ 2.61 (P < 0.001). Multiple analyses indicated that NLR (hazard ratio (HR) 1.65; 95 percent confidence interval (95% CI) 1.25-2.17), differentiation (HR 1.25; 95% CI 0.97-1.62) and TNM stage (HR 3.79; 95% CI 2.09-6.87) were independent prognostic factors for GBC. GBC patients in stage III/IV, NLR > 2.61 exhibited worse OS compared to patients with NLR ≤ 2.61 (P < 0.05). A prognostic evaluation model based on the independent prognostic factors was established. CONCLUSION: NLR is associated with GBC prognosis and is a potential prognostic marker for GBC, not only preoperatively but also postoperatively.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic significance of neutrophil to lymphocyte ratio in patients with gallbladder carcinoma BACKGROUND: Numerous literature suggest that the preoperative neutrophil to lymphocyte ratio (NLR) is correlated to the prognosis of various cancers. However, the prognostic significance of NLR in gallbladder carcinoma (GBC) remains to be determined. METHODS: Data from 316 GBC patients with surgical treatment were reviewed retrospectively. A receiver operating characteristic (ROC) curve was performed to determine an optimal cut-off value for NLR. The Kaplan-Meier method and Cox regression proportional hazard model were performed to evaluate prognostic factors. RESULTS: The optimal cut-off point for NLR was 2.61 according to the ROC curve. According to the univariable analysis, NLR, differentiation and TNM stage were associated with GBC prognosis. GBC patients with NLR > 2.61 have worsened 5-year overall survival (OS) compared to patients with NLR ≤ 2.61 (P < 0.001). Multiple analyses indicated that NLR (hazard ratio (HR) 1.65; 95 percent confidence interval (95% CI) 1.25-2.17), differentiation (HR 1.25; 95% CI 0.97-1.62) and TNM stage (HR 3.79; 95% CI 2.09-6.87) were independent prognostic factors for GBC. GBC patients in stage III/IV, NLR > 2.61 exhibited worse OS compared to patients with NLR ≤ 2.61 (P < 0.05). A prognostic evaluation model based on the independent prognostic factors was established. CONCLUSION: NLR is associated with GBC prognosis and is a potential prognostic marker for GBC, not only preoperatively but also postoperatively. PubMed","prediction_labels":"HUMAN"},{"cleaned":"disease free survival following resection non ductal periampullary cancers retrospective multicenter analysis background predictors recurrence following pancreaticoduodenectomy well described ductal periampullary cancers lack reliability non ductal tumors purpose study analyze disease free survival dfs define predictors recurrence following resection ampullary ac bile duct bdc duodenal cancers dc materials methods clinico pathological data patients operated 2001 2011 retrospectively reviewed effect lymphatic invasion specified using lymph node ratio lnr number positive nodes npn thresholds calculated likelihood ratio kaplan meier disease free survival dfs curves compared covariates log rank test multivariate logistic regression analyses performed identify predictors recurrence results 135 patients identified mean follow 49 35 months median dfs reached ac 36 18 months dc bdc respectively five year dfs 52 43 32 ac dc bdc respectively predictors recurrence t4 tumors neural invasion preoperative biliary drainage dc 3 positive nodes 4 loss bmi ac t3 t4 tumors bdc conclusion loss bmi 4 strong predictor recurrence ac recurrence risk increases total number lymph nodes invaded 0 1 3 4 stage influences recurrence bdc considering dc adverse effect preoperative biliary drainage validated randomized series pubmed","probabilities":0.9799733,"Title":"Disease-free survival following resection in non-ductal periampullary cancers: A retrospective multicenter analysis","Abstract":"BACKGROUND: Predictors of recurrence following pancreaticoduodenectomy are well described for ductal periampullary cancers but lack reliability for non-ductal tumors. The purpose of this study is to analyze the disease-free survival (DFS) and to define the predictors of recurrence following resection for ampullary (AC), bile duct (BDC) and duodenal cancers (DC). MATERIALS AND METHODS: Clinico-pathological data of patients operated on between 2001 and 2011 were retrospectively reviewed. The effect of lymphatic invasion was specified using the lymph node ratio (LNR) and the number of positive nodes (NPN), with thresholds calculated with the likelihood ratio. Kaplan-Meier disease-free survival (DFS) curves were compared for all covariates by a log-rank test. Multivariate logistic regression analyses were performed to identify predictors of recurrence. RESULTS: 135 patients were identified. Mean follow-up was 49 ± 35 months. Median DFS was not reached for AC and was 36 and 18 months for DC and BDC, respectively. Five-year DFS was 52%, 43% and 32% for AC, DC and BDC, respectively. Predictors of recurrence were T4 tumors, neural invasion and preoperative biliary drainage for DC, ≥3 positive nodes and ≥4% loss of BMI for AC, and T3-T4 tumors for BDC. CONCLUSION: Loss of BMI ≥4% is a strong predictor of recurrence in AC, and the recurrence risk increases with the total number of lymph nodes invaded (0; 1-3; ≥4). Only T stage influences recurrence for BDC. Considering DC, the adverse effect of preoperative biliary drainage should be validated in randomized series.","Source":"PubMed","category":"HUMAN","training_data":"Disease-free survival following resection in non-ductal periampullary cancers: A retrospective multicenter analysis BACKGROUND: Predictors of recurrence following pancreaticoduodenectomy are well described for ductal periampullary cancers but lack reliability for non-ductal tumors. The purpose of this study is to analyze the disease-free survival (DFS) and to define the predictors of recurrence following resection for ampullary (AC), bile duct (BDC) and duodenal cancers (DC). MATERIALS AND METHODS: Clinico-pathological data of patients operated on between 2001 and 2011 were retrospectively reviewed. The effect of lymphatic invasion was specified using the lymph node ratio (LNR) and the number of positive nodes (NPN), with thresholds calculated with the likelihood ratio. Kaplan-Meier disease-free survival (DFS) curves were compared for all covariates by a log-rank test. Multivariate logistic regression analyses were performed to identify predictors of recurrence. RESULTS: 135 patients were identified. Mean follow-up was 49 ± 35 months. Median DFS was not reached for AC and was 36 and 18 months for DC and BDC, respectively. Five-year DFS was 52%, 43% and 32% for AC, DC and BDC, respectively. Predictors of recurrence were T4 tumors, neural invasion and preoperative biliary drainage for DC, ≥3 positive nodes and ≥4% loss of BMI for AC, and T3-T4 tumors for BDC. CONCLUSION: Loss of BMI ≥4% is a strong predictor of recurrence in AC, and the recurrence risk increases with the total number of lymph nodes invaded (0; 1-3; ≥4). Only T stage influences recurrence for BDC. Considering DC, the adverse effect of preoperative biliary drainage should be validated in randomized series. PubMed","prediction_labels":"HUMAN"},{"cleaned":"extracellular vesicle treatment cholangiocarcinoma cells affects genes epithelial mesenchymal transition cell survival abstract available google scholar","probabilities":0.9467213,"Title":"Extracellular Vesicle Treatment Of Cholangiocarcinoma Cells Affects Genes Of Epithelial-Mesenchymal Transition And Cell Survival","Abstract":"Abstract not available","Source":"Google Scholar","category":"ANIMAL","training_data":"Extracellular Vesicle Treatment Of Cholangiocarcinoma Cells Affects Genes Of Epithelial-Mesenchymal Transition And Cell Survival Abstract not available Google Scholar","prediction_labels":"ANIMAL"},{"cleaned":"association optimal time interval re resection incidental gallbladder cancer overall survival multi institution analysis us extrahepatic biliary malignancy consortium importance current recommendation perform re resection select patients incidentally discovered gallbladder cancer optimal time interval re resection patient selection long term survival known objective assess association time interval initial cholecystectomy reoperation overall survival design setting participants cohort study conducted january 1 2000 december 31 2014 10 us academic institutions total 207 patients incidentally discovered gallbladder cancer underwent reoperation available data date initial cholecystectomy included exposures time interval initial cholecystectomy reoperation group less 4 weeks group b 4 8 weeks group c greater 8 weeks main outcomes measures primary outcome overall survival results 449 patients gallbladder cancer 207 cases 46 discovered incidentally underwent reoperation 3 different time intervals date original cholecystectomy group less 4 weeks 25 patients 12 b 4 8 weeks 91 patients 44 c 8 weeks 91 patients 44 mean sd ages patients groups b c 65 9 64 11 66 12 years respectively groups similar baseline demographics extent resection presence residual disease stage resection margin status lymph node involvement postoperative complications patients underwent reoperation 4 8 weeks longest median overall survival group b 40 4 months compared underwent early group 17 4 months late group c 22 4 months reoperation log rank p 03 group c time intervals vs group b presence residual disease r2 resection advanced stage lymph node involvement associated decreased overall survival univariable cox regression group hazard ratio 2 63 95 ci 1 25 5 54 group c hazard ratio 2 07 95 ci 1 17 3 66 time intervals vs group b r2 resection hazard ratio 2 69 95 ci 1 27 5 69 advanced tstage hazard ratio 1 85 95 ci 1 11 3 08 persisted multivariable cox regression analysis conclusions relevance optimal time interval re resection incidentally discovered gallbladder cancer appears 4 8 weeks initial cholecystectomy pubmed","probabilities":0.9799733,"Title":"Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival: A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium","Abstract":"IMPORTANCE: The current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The optimal time interval for re-resection for both patient selection and long-term survival is not known. OBJECTIVE: To assess the association of time interval from the initial cholecystectomy to reoperation with overall survival. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted from January 1, 2000, to December 31, 2014 at 10 US academic institutions. A total of 207 patients with incidentally discovered gallbladder cancer who underwent reoperation and had available data on the date of their initial cholecystectomy were included. EXPOSURES: Time interval from the initial cholecystectomy to reoperation: group A: less than 4 weeks; group B: 4 to 8 weeks; and group C: greater than 8 weeks. MAIN OUTCOMES AND MEASURES: Primary outcome was overall survival. RESULTS: Of 449 patients with gallbladder cancer, 207 cases (46%) were discovered incidentally and underwent reoperation at 3 different time intervals from the date of the original cholecystectomy: group A: less than 4 weeks (25 patients, 12%); B: 4 to 8 weeks (91 patients, 44%); C: more than 8 weeks (91 patients, 44%). The mean (SD) ages of patients in groups A, B, and C were 65 (9), 64 (11), and 66 (12) years, respectively. All groups were similar for baseline demographics, extent of resection, presence of residual disease, T stage, resection margin status, lymph node involvement, and postoperative complications. Patients who underwent reoperation between 4 and 8 weeks had the longest median overall survival (group B: 40.4 months) compared with those who underwent early (group A: 17.4 months) or late (group C: 22.4 months) reoperation (log-rank P = .03). Group A and C time intervals (vs group B), presence of residual disease, an R2 resection, advanced T stage, and lymph node involvement were associated with decreased overall survival on univariable Cox regression. Only group A (hazard ratio, 2.63; 95% CI, 1.25-5.54) and group C (hazard ratio, 2.07; 95% CI, 1.17-3.66) time intervals (vs group B), R2 resection (hazard ratio, 2.69; 95% CI, 1.27-5.69), and advanced Tstage (hazard ratio, 1.85; 95% CI, 1.11-3.08) persisted on multivariable Cox regression analysis. CONCLUSIONS AND RELEVANCE: The optimal time interval for re-resection for incidentally discovered gallbladder cancer appears to be between 4 and 8 weeks after the initial cholecystectomy.","Source":"PubMed","category":"HUMAN","training_data":"Association of Optimal Time Interval to Re-resection for Incidental Gallbladder Cancer With Overall Survival: A Multi-Institution Analysis From the US Extrahepatic Biliary Malignancy Consortium IMPORTANCE: The current recommendation is to perform re-resection for select patients with incidentally discovered gallbladder cancer. The optimal time interval for re-resection for both patient selection and long-term survival is not known. OBJECTIVE: To assess the association of time interval from the initial cholecystectomy to reoperation with overall survival. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was conducted from January 1, 2000, to December 31, 2014 at 10 US academic institutions. A total of 207 patients with incidentally discovered gallbladder cancer who underwent reoperation and had available data on the date of their initial cholecystectomy were included. EXPOSURES: Time interval from the initial cholecystectomy to reoperation: group A: less than 4 weeks; group B: 4 to 8 weeks; and group C: greater than 8 weeks. MAIN OUTCOMES AND MEASURES: Primary outcome was overall survival. RESULTS: Of 449 patients with gallbladder cancer, 207 cases (46%) were discovered incidentally and underwent reoperation at 3 different time intervals from the date of the original cholecystectomy: group A: less than 4 weeks (25 patients, 12%); B: 4 to 8 weeks (91 patients, 44%); C: more than 8 weeks (91 patients, 44%). The mean (SD) ages of patients in groups A, B, and C were 65 (9), 64 (11), and 66 (12) years, respectively. All groups were similar for baseline demographics, extent of resection, presence of residual disease, T stage, resection margin status, lymph node involvement, and postoperative complications. Patients who underwent reoperation between 4 and 8 weeks had the longest median overall survival (group B: 40.4 months) compared with those who underwent early (group A: 17.4 months) or late (group C: 22.4 months) reoperation (log-rank P = .03). Group A and C time intervals (vs group B), presence of residual disease, an R2 resection, advanced T stage, and lymph node involvement were associated with decreased overall survival on univariable Cox regression. Only group A (hazard ratio, 2.63; 95% CI, 1.25-5.54) and group C (hazard ratio, 2.07; 95% CI, 1.17-3.66) time intervals (vs group B), R2 resection (hazard ratio, 2.69; 95% CI, 1.27-5.69), and advanced Tstage (hazard ratio, 1.85; 95% CI, 1.11-3.08) persisted on multivariable Cox regression analysis. CONCLUSIONS AND RELEVANCE: The optimal time interval for re-resection for incidentally discovered gallbladder cancer appears to be between 4 and 8 weeks after the initial cholecystectomy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"modified staging classification intrahepatic cholangiocarcinoma based sixth seventh editions ajcc uicc tnm staging systems intrahepatic cholangiocarcinoma icc differentiated hepatocellular carcinoma defined american joint committee cancer ajcc 6th edition staging manual using revised staging system described ajcc 7th edition staging manual study conducted analyze application ajcc 6th 7th edition staging classifications evaluate modified staging classification potentially reduce limitations associated different ajcc staging systems compared prognostic value cancer staging using data surveillance epidemiology end results database n 2124 kaplan meier method cox regression models used analyze survival harrell concordance index c index used analyze discriminative abilities cancer staging patients stages ii disease found similar prognoses according 6th edition staging system using 7th edition staging system low proportion patients stage iii disease 5 0 hazard ratio hr stage iii disease comparable stage iv disease stage iii iv 2 653 2 694 modified ajcc staging classification adopting 7th edition n m definitions 6th edition staging definitions consequently proportion patients stage iii disease increased 22 8 hr stage iv disease higher stage iii disease stage iii iv 2 425 2 956 meanwhile c index modified ajcc staging system 0 721 95 ci 0 696 0 745 significantly higher ajcc 7th edition staging system 0 694 p 001 ajcc 6th edition staging system 0 712 p 033 moreover stratified data differences stages identified using modified ajcc staging classification significant especially among patients 60 years age white patients patients underwent surgery findings suggest modified ajcc staging classification may applicable staging icc adopted clinical practice pubmed","probabilities":0.9799733,"Title":"Modified staging classification for intrahepatic cholangiocarcinoma based on the sixth and seventh editions of the AJCC/UICC TNM staging systems","Abstract":"Intrahepatic cholangiocarcinoma (ICC) was differentiated from hepatocellular carcinoma, as defined in the American Joint Committee on Cancer (AJCC) 6th edition staging manual, using the revised staging system described in the AJCC 7th edition staging manual. This study was conducted to analyze the application of the AJCC 6th and 7th edition staging classifications and to evaluate a modified staging classification to potentially reduce the limitations associated with the different AJCC staging systems.We compared the prognostic value of cancer staging using data from the Surveillance, Epidemiology, and End Results database (N = 2124). The Kaplan-Meier method and Cox regression models were used to analyze survival. The Harrell concordance index (C-index) was used to analyze the discriminative abilities of cancer staging.Patients with stages I and II disease were found to have similar prognoses according to the 6th edition staging system. Using the 7th edition staging system, a low proportion of patients had stage III disease (5.0%), and the hazard ratio (HR) for stage III disease was comparable to that of stage IV disease (stage III and IV, 2.653 and 2.694). We modified the AJCC staging classification by adopting the 7th edition T, N, and M definitions and the 6th edition staging definitions. Consequently, the proportion of patients with stage III disease increased (22.8%). The HR for stage IV disease was higher than that for stage III disease (stage III and IV, 2.425 and 2.956). Meanwhile, the C-index of the modified AJCC staging system was 0.721 (95% CI: 0.696-0.745), which was significantly higher than the AJCC 7th edition staging system (0.694, P < .001), and the AJCC 6th edition staging system (0.712, P = .033). Moreover, in the stratified data, the differences between the stages identified using the modified AJCC staging classification were significant, especially among patients over 60 years in age, white patients and patients who underwent surgery.These findings suggest that the modified AJCC staging classification may be applicable to the staging of ICC and can be adopted in clinical practice.","Source":"PubMed","category":"HUMAN","training_data":"Modified staging classification for intrahepatic cholangiocarcinoma based on the sixth and seventh editions of the AJCC/UICC TNM staging systems Intrahepatic cholangiocarcinoma (ICC) was differentiated from hepatocellular carcinoma, as defined in the American Joint Committee on Cancer (AJCC) 6th edition staging manual, using the revised staging system described in the AJCC 7th edition staging manual. This study was conducted to analyze the application of the AJCC 6th and 7th edition staging classifications and to evaluate a modified staging classification to potentially reduce the limitations associated with the different AJCC staging systems.We compared the prognostic value of cancer staging using data from the Surveillance, Epidemiology, and End Results database (N = 2124). The Kaplan-Meier method and Cox regression models were used to analyze survival. The Harrell concordance index (C-index) was used to analyze the discriminative abilities of cancer staging.Patients with stages I and II disease were found to have similar prognoses according to the 6th edition staging system. Using the 7th edition staging system, a low proportion of patients had stage III disease (5.0%), and the hazard ratio (HR) for stage III disease was comparable to that of stage IV disease (stage III and IV, 2.653 and 2.694). We modified the AJCC staging classification by adopting the 7th edition T, N, and M definitions and the 6th edition staging definitions. Consequently, the proportion of patients with stage III disease increased (22.8%). The HR for stage IV disease was higher than that for stage III disease (stage III and IV, 2.425 and 2.956). Meanwhile, the C-index of the modified AJCC staging system was 0.721 (95% CI: 0.696-0.745), which was significantly higher than the AJCC 7th edition staging system (0.694, P < .001), and the AJCC 6th edition staging system (0.712, P = .033). Moreover, in the stratified data, the differences between the stages identified using the modified AJCC staging classification were significant, especially among patients over 60 years in age, white patients and patients who underwent surgery.These findings suggest that the modified AJCC staging classification may be applicable to the staging of ICC and can be adopted in clinical practice. PubMed","prediction_labels":"HUMAN"},{"cleaned":"prognostic comparison longitudinal margin status distal bile duct cancer r0 first bile duct resection versus r0 additional resection background study investigated survival differences following intra operative frozen section examination bile duct resection margins final longitudinal margin status lms distal bile duct cancer bdc methods one hundred ninety three patients underwent whipple operation curative resection distal bdc 2008 2016 patients sorted two three groups according lms frozen sections final pathological specimen results r0 first bile duct resection primary r0 r0 additional resection secondary r0 evidence residual carcinoma fr0 carcinoma situ high grade dysplasia fr1 cis hgd invasive carcinoma fr1 inv survival prognostic factors according lms analyzed results final r0 ratio increased 82 3 90 1 additional resection 5 year overall survival os primary secondary r0 60 8 46 1 p 0 969 disease free survival primary secondary r0 54 6 54 9 p 0 903 5 year os fr0 fr1 cis hgd fr1 inv 59 3 59 5 14 3 p 0 842 lms bile duct independent prognostic factor multivariable analyses conclusions r0 final lms achieved help improve survival regardless r0 additional resection avoided remaining invasive cancer longitudinal margin whenever possible pubmed","probabilities":0.9799733,"Title":"Prognostic comparison of the longitudinal margin status in distal bile duct cancer: R0 on first bile duct resection versus R0 after additional resection","Abstract":"BACKGROUND: This study investigated survival differences following intra-operative frozen-section examination of bile duct resection margins and final longitudinal margin status (LMS) in distal bile duct cancer (BDC). METHODS: One hundred and ninety-three patients underwent Whipple's operation for curative resection of distal BDC from 2008 to 2016. Patients were sorted into two and three groups according to LMS of the frozen-sections and the final pathological specimen results: R0 on first bile duct resection (primary R0), R0 after additional resection (secondary R0), and no evidence of residual carcinoma (FR0), carcinoma in situ or high-grade dysplasia (FR1-CIS/HGD), or invasive carcinoma (FR1-INV). Survival and prognostic factors according to LMS were analyzed. RESULTS: The final R0 ratio increased from 82.3% to 90.1% through additional resection. The 5-year overall survival (OS) of primary and secondary R0 were 60.8%, 46.1% (P = 0.969). And disease-free survival of primary and secondary R0 were 54.6%, 54.9% (P = 0.903). The 5-year OS after FR0, FR1-CIS/HGD, FR1-INV were 59.3%, 59.5%, 14.3% (P = 0.842). LMS of the bile duct was an independent prognostic factor by multivariable analyses. CONCLUSIONS: If R0 of final LMS was achieved, it would help to improve survival regardless of R0 through additional resection. And, it should be avoided remaining invasive cancer at the longitudinal margin whenever possible.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic comparison of the longitudinal margin status in distal bile duct cancer: R0 on first bile duct resection versus R0 after additional resection BACKGROUND: This study investigated survival differences following intra-operative frozen-section examination of bile duct resection margins and final longitudinal margin status (LMS) in distal bile duct cancer (BDC). METHODS: One hundred and ninety-three patients underwent Whipple's operation for curative resection of distal BDC from 2008 to 2016. Patients were sorted into two and three groups according to LMS of the frozen-sections and the final pathological specimen results: R0 on first bile duct resection (primary R0), R0 after additional resection (secondary R0), and no evidence of residual carcinoma (FR0), carcinoma in situ or high-grade dysplasia (FR1-CIS/HGD), or invasive carcinoma (FR1-INV). Survival and prognostic factors according to LMS were analyzed. RESULTS: The final R0 ratio increased from 82.3% to 90.1% through additional resection. The 5-year overall survival (OS) of primary and secondary R0 were 60.8%, 46.1% (P = 0.969). And disease-free survival of primary and secondary R0 were 54.6%, 54.9% (P = 0.903). The 5-year OS after FR0, FR1-CIS/HGD, FR1-INV were 59.3%, 59.5%, 14.3% (P = 0.842). LMS of the bile duct was an independent prognostic factor by multivariable analyses. CONCLUSIONS: If R0 of final LMS was achieved, it would help to improve survival regardless of R0 through additional resection. And, it should be avoided remaining invasive cancer at the longitudinal margin whenever possible. PubMed","prediction_labels":"HUMAN"},{"cleaned":"postoperative morbidity detriments long term survival radical resection carcinoma gall bladder objective retrospective analysis prospectively maintained database aimed investigate impact postoperative morbidity long term survival surgery carcinoma gall bladder methods 2002 2011 110 patients admitted suspected carcinoma gall bladder clinical radiological examination 65 patients underwent radical resection 11 65 turned benign disease 6 xanthogranulomatous cholecystitis one hilar cholangiocarcinoma 4 chronic cholecystitison final hpr perioperative details long term follow 54 patients carcinoma collected prospective database univariate multivariate models used identify potential prognostic factors impact post operative complications long term survival patients divided two groups respect presence absence postoperative complications groups comparable terms demographic intra operative histopathological details adjuvant treatment received results 52 54 patients underwent r0 resection 30 day 90 day mortality 3 7 1 8 complication rate 40 major complication 20 clavien grade 3 5 among 54 patients 24 deceased due metastasis 14 patients lost follow remaining 14 follow mean overall survival patients 25 3 5 months using univariate multivariate analysis preoperative jaundice post operative complications n1 status pathological organ involvement associated poor overall disease free survival postoperative complication independent factor associated decreased disease free survival excluding patients 30 90 days mortality mean overall survival patients complication 16 5 months compared 32 4 months patients complications p 0 018 meandfs patient post operative complication 15 months compared 30 3 months patients complications p 0 027 conclusion presence post operative complications affect short term results radical surgery carcinoma gall bladder long term oncological outcomes also adversely affected long term outcomes improved efforts reduce postoperative complications google scholar","probabilities":0.9799733,"Title":"Postoperative Morbidity Detriments Long Term Survival After Radical Resection For Carcinoma Gall Bladder","Abstract":"Objective:  Retrospective analysis of prospectively maintained database aimed to investigate the impact of postoperative morbidity on long term survival after surgery for carcinoma gall bladder. Methods:  Between 2002 and 2011, 110 patients were admitted suspected to have carcinoma gall bladder on clinical and radiological examination. 65 patients underwent radical resection. 11/65 turned out to have benign disease (6 had xanthogranulomatous cholecystitis, one had hilar cholangiocarcinoma and 4 had chronic cholecystitison final HPR). Perioperative details and long term follow up of 54 patients with carcinoma were collected from prospective database. Univariate and multivariate models were used to identify potential prognostic factors and impact of post operative complications on long term survival. Patients were divided into two groups with respect to presence or absence of postoperative complications. Both the groups were comparable in terms of demographic, intra‐operative, histopathological details and adjuvant treatment received. Results:  52/54 patients underwent R0 resection. 30 day and 90 day mortality was 3.7% and 1.8%. Over all complication rate was 40% with major complication in 20%(Clavien grade 3–5). Among 54 patients; 24 were deceased due to metastasis. 14 patients were lost to follow up and remaining 14 are in follow up. Mean overall survival in these patients was 25 ± 3.5 months. Using Univariate and multivariate analysis preoperative jaundice, post‐operative complications, N1 status and pathological organ involvement were associated with poor overall and disease free survival. Postoperative complication was an independent factor associated with decreased over all and disease free survival. After excluding the patients with 30 an 90 days mortality, mean overall survival for patients with complication was 16.5 months compared to 32.4 months for patients with no complications (p = 0.018). The meanDFS for patient with post operative complication was 15 months compared to 30.3 months for patients with no complications (p = 0.027). Conclusion:  The presence of post operative complications not only affect the short term results of radical surgery for carcinoma gall bladder, but long term oncological outcomes are also adversely affected. Long term outcomes can be improved with efforts to reduce postoperative complications.","Source":"Google Scholar","category":"HUMAN","training_data":"Postoperative Morbidity Detriments Long Term Survival After Radical Resection For Carcinoma Gall Bladder Objective:  Retrospective analysis of prospectively maintained database aimed to investigate the impact of postoperative morbidity on long term survival after surgery for carcinoma gall bladder. Methods:  Between 2002 and 2011, 110 patients were admitted suspected to have carcinoma gall bladder on clinical and radiological examination. 65 patients underwent radical resection. 11/65 turned out to have benign disease (6 had xanthogranulomatous cholecystitis, one had hilar cholangiocarcinoma and 4 had chronic cholecystitison final HPR). Perioperative details and long term follow up of 54 patients with carcinoma were collected from prospective database. Univariate and multivariate models were used to identify potential prognostic factors and impact of post operative complications on long term survival. Patients were divided into two groups with respect to presence or absence of postoperative complications. Both the groups were comparable in terms of demographic, intra‐operative, histopathological details and adjuvant treatment received. Results:  52/54 patients underwent R0 resection. 30 day and 90 day mortality was 3.7% and 1.8%. Over all complication rate was 40% with major complication in 20%(Clavien grade 3–5). Among 54 patients; 24 were deceased due to metastasis. 14 patients were lost to follow up and remaining 14 are in follow up. Mean overall survival in these patients was 25 ± 3.5 months. Using Univariate and multivariate analysis preoperative jaundice, post‐operative complications, N1 status and pathological organ involvement were associated with poor overall and disease free survival. Postoperative complication was an independent factor associated with decreased over all and disease free survival. After excluding the patients with 30 an 90 days mortality, mean overall survival for patients with complication was 16.5 months compared to 32.4 months for patients with no complications (p = 0.018). The meanDFS for patient with post operative complication was 15 months compared to 30.3 months for patients with no complications (p = 0.027). Conclusion:  The presence of post operative complications not only affect the short term results of radical surgery for carcinoma gall bladder, but long term oncological outcomes are also adversely affected. Long term outcomes can be improved with efforts to reduce postoperative complications. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"correlation nrf2 ho 1 mrp3 gallbladder cancer relationships clinicopathologic features survival background gallbladder cancer gc considered relatively rare malignancy extensively poor prognosis guide clinicians selecting treatment options gc patients reliable markers predictive poor clinical outcome desirable study analyzed correlation nf e2 related factor 2 nrf2 heme oxygenase 1 ho 1 multidrug resistance related protein 3 mrp3 gc relationships clinicopathologic features survival material methods immunohistochemically investigated 59 specimens gallbladder adenocarcinoma tissues using nrf2 ho 1 mrp3 antibodies results significant correlations high level nrf2 ho 1 mrp3 expression tumor differentiation nevin staging metastasis significant positive correlations found expression status nrf2 ho 1 mrp3 r 0 38 p 0 008 r 0 59 p 0 001 respectively high nrf2 expression significantly associated shorter overall survival times univariate analysis log rank test p 0 001 also identified independent prognostic factor multivariate analysis p 0 035 conclusions nrf2 ho 1 mrp3 associated certain clinicopathologic parameters gc evaluation nrf2 expression may important factor identifying poor prognostic group gc pubmed","probabilities":0.9285714,"Title":"Correlation of Nrf2, HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathologic features and survival","Abstract":"BACKGROUND: Gallbladder cancer (GC) is considered a relatively rare malignancy with extensively poor prognosis. To guide clinicians in selecting treatment options for GC patients, reliable markers predictive of poor clinical outcome are desirable. This study analyzed the correlation of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and multidrug resistance-related protein 3 (MRP3) in GC and their relationships to clinicopathologic features and survival. MATERIAL AND METHODS: We immunohistochemically investigated 59 specimens of gallbladder adenocarcinoma tissues using Nrf2, HO-1, and MRP3 antibodies. RESULTS: There were significant correlations between the high level of Nrf2, HO-1, and MRP3 expression and the tumor differentiation, Nevin staging, and metastasis. Significant positive correlations were found between the expression status of Nrf2 and that of HO-1 and MRP3 (r = 0.38, P = 0.008 and r = 0.59, P < 0.001, respectively). High Nrf2 expression was significantly associated with shorter overall survival times in univariate analysis (log-rank test, P < 0.001), being also identified as an independent prognostic factor in multivariate analysis (P = 0.035). CONCLUSIONS: Nrf2, HO-1, and MRP3 were associated with certain clinicopathologic parameters in GC. Evaluation of Nrf2 expression may be an important factor in identifying a poor prognostic group of GC.","Source":"PubMed","category":"ANIMAL","training_data":"Correlation of Nrf2, HO-1, and MRP3 in gallbladder cancer and their relationships to clinicopathologic features and survival BACKGROUND: Gallbladder cancer (GC) is considered a relatively rare malignancy with extensively poor prognosis. To guide clinicians in selecting treatment options for GC patients, reliable markers predictive of poor clinical outcome are desirable. This study analyzed the correlation of NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and multidrug resistance-related protein 3 (MRP3) in GC and their relationships to clinicopathologic features and survival. MATERIAL AND METHODS: We immunohistochemically investigated 59 specimens of gallbladder adenocarcinoma tissues using Nrf2, HO-1, and MRP3 antibodies. RESULTS: There were significant correlations between the high level of Nrf2, HO-1, and MRP3 expression and the tumor differentiation, Nevin staging, and metastasis. Significant positive correlations were found between the expression status of Nrf2 and that of HO-1 and MRP3 (r = 0.38, P = 0.008 and r = 0.59, P < 0.001, respectively). High Nrf2 expression was significantly associated with shorter overall survival times in univariate analysis (log-rank test, P < 0.001), being also identified as an independent prognostic factor in multivariate analysis (P = 0.035). CONCLUSIONS: Nrf2, HO-1, and MRP3 were associated with certain clinicopathologic parameters in GC. Evaluation of Nrf2 expression may be an important factor in identifying a poor prognostic group of GC. PubMed","prediction_labels":"ANIMAL"},{"cleaned":"cholangiocarcinoma epidemiology risk factors pathogenesis diagnosis cholangiocarcinoma cca rare tumor arising epithelium intrahepatic extrahepatic bile ducts rarely diagnosed 40 years age except patients primary sclerosing cholangitis cca usually clinically silent tumor obstructs bile ducts carbohydrate antigen 19 9 commonly used tumor marker magnetic resonance cholangiopancreatography best available imaging modality cca endoscopic retrograde cholangiopancreatography cholangioscopy allow tissue acquisition positron emission tomography may play role identifying occult metastases tissue diagnosis obtained brush cytology bile duct biopsy pubmed","probabilities":0.7966102,"Title":"Cholangiocarcinoma: epidemiology, risk factors, pathogenesis, and diagnosis","Abstract":"Cholangiocarcinoma (CCA) is a rare tumor arising from the epithelium of the intrahepatic or the extrahepatic bile ducts. It is rarely diagnosed before 40 years of age except in patients with primary sclerosing cholangitis. CCA is usually clinically silent until the tumor obstructs the bile ducts. Carbohydrate antigen 19-9 is the most commonly used tumor marker, and magnetic resonance cholangiopancreatography is the best available imaging modality for CCA. Endoscopic retrograde cholangiopancreatography and cholangioscopy allow tissue acquisition. Positron emission tomography may play a role in identifying occult metastases. Tissue diagnosis is obtained by brush cytology or bile duct biopsy.","Source":"PubMed","category":"HUMAN","training_data":"Cholangiocarcinoma: epidemiology, risk factors, pathogenesis, and diagnosis Cholangiocarcinoma (CCA) is a rare tumor arising from the epithelium of the intrahepatic or the extrahepatic bile ducts. It is rarely diagnosed before 40 years of age except in patients with primary sclerosing cholangitis. CCA is usually clinically silent until the tumor obstructs the bile ducts. Carbohydrate antigen 19-9 is the most commonly used tumor marker, and magnetic resonance cholangiopancreatography is the best available imaging modality for CCA. Endoscopic retrograde cholangiopancreatography and cholangioscopy allow tissue acquisition. Positron emission tomography may play a role in identifying occult metastases. Tissue diagnosis is obtained by brush cytology or bile duct biopsy. PubMed","prediction_labels":"HUMAN"},{"cleaned":"lncrnas potential molecular biomarkers clinicopathology prognosis cholangiocarcinoma systematic review meta analysis background cholangiocarcinoma cca second common fatal primary hepatobiliary malignant carcinoma characterized early invasion extremely poor outcomes therefore necessary identify novel biomarker better diagnose caa predict prognosis recently emerging evidence revealed lncrnas play important role tumorigenesis progression caa order support search novel diagnostic prognostic biomarkers caa conducted meta analysis analyze published association lncrna expression clinical value caa methods eligible studies pooled analyzed according inclusion exclusion criteria comprehensive literature search stata 14 0 software used analyze data relevant studies construct forest plot different effect sizes selected meta analysis results total 24 publications included meta analysis review full text 16 articles studied association lncrnas clinicopathological characteristics 2 discussing diagnosis 16 discussing prognosis results showed overexpression ccat1 significantly correlated tumor stage ii vs iii iv 4 99 95 ci 2 77 8 99 p 0 001 lymph node metastasis cca 4 75 95 ci 2 65 8 52 p 0 001 furthermore elevated ccat lncrna family expression predicted shorter overall survival hr 2 09 95 ci 1 17 3 00 p 0 001 especially ccat2 upregulation ccat2 also obviously associated tumor stage cca 5 29 95 ci 2 64 10 58 p 0 001 conclusion first meta analysis assess relationship expression lncrnas clinical values patients cca lncrnas function potential molecular biomarkers clinicopathology prognosis cca stn","probabilities":0.9799733,"Title":"Lncrnas As Potential Molecular Biomarkers In The Clinicopathology And Prognosis Of Cholangiocarcinoma: A Systematic Review And Meta-Analysis","Abstract":"Background: Cholangiocarcinoma (CCA) is the second most common fatal primary hepatobiliary malignant carcinoma, characterized by early invasion and extremely poor outcomes. It is therefore necessary to identify a novel biomarker to better diagnose CAA and predict its prognosis. Recently, emerging evidence has revealed that some lncRNAs play an important role in the tumorigenesis and progression of CAA. In order to support this search for novel diagnostic and prognostic biomarkers for CAA, we conducted a meta-analysis to analyze the published association between lncRNA expression and its clinical value in CAA. \r\n\r\n Methods: Eligible studies were pooled and analyzed according to our inclusion and exclusion criteria after a comprehensive literature search. Stata 14.0 software was used to analyze the data from relevant studies and to construct a forest plot. Different effect sizes were selected for the meta-analysis. \r\n\r\n Results: In total, 24 publications were included in this meta-analysis. After review of their full-text, 16 articles studied the association between lncRNAs and clinicopathological characteristics, 2 discussing diagnosis and 16 discussing prognosis. Our results showed that overexpression of CCAT1 was significantly correlated with tumor stage (I + II vs III + IV) (OR, 4.99; 95% CI 2.77-8.99; P<0.001) and lymph node metastasis in CCA (OR, 4.75; 95% CI 2.65-8.52; P<0.001). Furthermore, elevated CCAT lncRNA family expression predicted a shorter overall survival (HR, 2.09; 95% CI 1.17-3.00; P<0.001), especially CCAT2. Upregulation of CCAT2 was also obviously associated with tumor stage in CCA (OR, 5.29; 95% CI 2.64-10.58; P=0.001). \r\n\r\n Conclusion: This is the first meta-analysis to assess the relationship between expression of lncRNAs and the clinical values of patients with CCA. lncRNAs can function as potential molecular biomarkers of the clinicopathology and prognosis of CCA.","Source":"STN","category":"HUMAN","training_data":"Lncrnas As Potential Molecular Biomarkers In The Clinicopathology And Prognosis Of Cholangiocarcinoma: A Systematic Review And Meta-Analysis Background: Cholangiocarcinoma (CCA) is the second most common fatal primary hepatobiliary malignant carcinoma, characterized by early invasion and extremely poor outcomes. It is therefore necessary to identify a novel biomarker to better diagnose CAA and predict its prognosis. Recently, emerging evidence has revealed that some lncRNAs play an important role in the tumorigenesis and progression of CAA. In order to support this search for novel diagnostic and prognostic biomarkers for CAA, we conducted a meta-analysis to analyze the published association between lncRNA expression and its clinical value in CAA. \r\n\r\n Methods: Eligible studies were pooled and analyzed according to our inclusion and exclusion criteria after a comprehensive literature search. Stata 14.0 software was used to analyze the data from relevant studies and to construct a forest plot. Different effect sizes were selected for the meta-analysis. \r\n\r\n Results: In total, 24 publications were included in this meta-analysis. After review of their full-text, 16 articles studied the association between lncRNAs and clinicopathological characteristics, 2 discussing diagnosis and 16 discussing prognosis. Our results showed that overexpression of CCAT1 was significantly correlated with tumor stage (I + II vs III + IV) (OR, 4.99; 95% CI 2.77-8.99; P<0.001) and lymph node metastasis in CCA (OR, 4.75; 95% CI 2.65-8.52; P<0.001). Furthermore, elevated CCAT lncRNA family expression predicted a shorter overall survival (HR, 2.09; 95% CI 1.17-3.00; P<0.001), especially CCAT2. Upregulation of CCAT2 was also obviously associated with tumor stage in CCA (OR, 5.29; 95% CI 2.64-10.58; P=0.001). \r\n\r\n Conclusion: This is the first meta-analysis to assess the relationship between expression of lncRNAs and the clinical values of patients with CCA. lncRNAs can function as potential molecular biomarkers of the clinicopathology and prognosis of CCA. STN","prediction_labels":"HUMAN"},{"cleaned":"depth hepatic infiltration lymph node swelling factors considering surgery t2 4 gallbladder carcinoma patients background aim aim present study clarify degree hepatic infiltration lymph node swelling gallbladder carcinoma gbc held deciding factors t2 4 gbc patients undergo surgery patients methods fifty consecutive patients t2 4 gbc underwent surgery reviewed retrospectively investigated preoperative information imaging factors predictors survival results estimated overall survival patients lower patients hepatic infiltration 5 mm n 12 5 mm n 38 p 0 003 multivariate analyses demonstrated liver infiltration 5 mm 2 251 95 ci 0 906 5 596 p 0 081 lymph node swelling 2 462 95 ci 1 034 5 859 p 0 042 risk factors poor survival conclusion results suggested 5 mm liver infiltration lymph node swelling may serve deciding factors surgery consideration gbc patients pubmed","probabilities":0.9799733,"Title":"Depth of Hepatic Infiltration and Lymph Node Swelling as Factors for Considering Surgery for T2-4 Gallbladder Carcinoma Patients","Abstract":"BACKGROUND/AIM: The aim of the present study was to clarify if the degree of hepatic infiltration and lymph node swelling of gallbladder carcinoma (GBC) should be held as deciding factors for T2-4 GBC patients to undergo surgery. PATIENTS AND METHODS: Fifty consecutive patients with T2-4 GBC who underwent surgery were reviewed retrospectively. We investigated the preoperative information and imaging factors as predictors of survival. RESULTS: The estimated overall survival in all patients was lower in patients with hepatic infiltration ≥5 mm (n=12) than in those with <5 mm (n=38) (p=0.003). Multivariate analyses demonstrated that liver infiltration ≥5 mm (OR=2.251; 95%CI=0.906-5.596, p=0.081) and lymph node swelling (OR=2.462; 95%CI=1.034-5.859, p=0.042) were risk factors of poor survival. CONCLUSION: Our results suggested that ≥5 mm liver infiltration and lymph node swelling may serve as deciding factors for surgery consideration in GBC patients.","Source":"PubMed","category":"HUMAN","training_data":"Depth of Hepatic Infiltration and Lymph Node Swelling as Factors for Considering Surgery for T2-4 Gallbladder Carcinoma Patients BACKGROUND/AIM: The aim of the present study was to clarify if the degree of hepatic infiltration and lymph node swelling of gallbladder carcinoma (GBC) should be held as deciding factors for T2-4 GBC patients to undergo surgery. PATIENTS AND METHODS: Fifty consecutive patients with T2-4 GBC who underwent surgery were reviewed retrospectively. We investigated the preoperative information and imaging factors as predictors of survival. RESULTS: The estimated overall survival in all patients was lower in patients with hepatic infiltration ≥5 mm (n=12) than in those with <5 mm (n=38) (p=0.003). Multivariate analyses demonstrated that liver infiltration ≥5 mm (OR=2.251; 95%CI=0.906-5.596, p=0.081) and lymph node swelling (OR=2.462; 95%CI=1.034-5.859, p=0.042) were risk factors of poor survival. CONCLUSION: Our results suggested that ≥5 mm liver infiltration and lymph node swelling may serve as deciding factors for surgery consideration in GBC patients. PubMed","prediction_labels":"HUMAN"},{"cleaned":"survival outcome prognostic factors pancreatoduodenectomy distal bile duct carcinoma retrospective multicenter study purpose pancreatoduodenectomy common operative procedure performed distal bile duct carcinoma data outcome surgery rare malignancy scarce especially western countries purpose study explore prognostic factors outcome pancreatoduodenectomy distal bile duct carcinoma methods patients receiving pancreatoduodenectomy distal bile duct carcinoma identified institutional databases five german one russian academic centers pancreatic surgery univariable multivariable general linear model kaplan meier method cox regression used identify prognostic factors postoperative mortality overall survival results n 228 patients operated 1994 2015 included reoperation 5 38 95 ci 1 51 19 22 p 0 010 grade b c postpancreatectomy hemorrhage 3 73 95 ci 1 13 12 35 p 0 031 grade b c postoperative pancreatic fistula 4 29 95 ci 1 25 14 72 p 0 038 advanced age 4 00 95 ci 1 12 14 03 p 0 033 independent risk factors hospital mortality multivariable analysis median survival 29 months 5 year survival 27 positive resection margin hr 2 07 95 ci 1 29 3 33 p 0 003 high tumor grade hr 1 71 95 ci 1 13 2 58 p 0 010 lymph node hr 1 68 95 ci 1 13 2 51 p 0 011 distant metastases hr 2 70 95 ci 1 21 5 58 p 0 014 well severe non fatal postoperative complications hr 1 64 95 ci 1 04 2 58 p 0 033 independent negative prognostic factors survival multivariable analysis conclusion distant metastases positive resection margin strongest negative prognostic factors survival pancreatoduodenectomy distal bile duct carcinoma thus surgery curative intent warranted patients local disease r0 resection feasible pubmed","probabilities":0.9799733,"Title":"Survival outcome and prognostic factors after pancreatoduodenectomy for distal bile duct carcinoma: a retrospective multicenter study","Abstract":"PURPOSE: Pancreatoduodenectomy is the most common operative procedure performed for distal bile duct carcinoma. Data on outcome after surgery for this rare malignancy is scarce, especially from western countries. The purpose of this study is to explore the prognostic factors and outcome after pancreatoduodenectomy for distal bile duct carcinoma. METHODS: Patients receiving pancreatoduodenectomy for distal bile duct carcinoma were identified from institutional databases of five German and one Russian academic centers for pancreatic surgery. Univariable and multivariable general linear model, Kaplan-Meier method, and Cox regression were used to identify prognostic factors for postoperative mortality and overall survival. RESULTS: N = 228 patients operated from 1994 to 2015 were included. Reoperation (OR 5.38, 95%CI 1.51-19.22, p = 0.010), grade B/C postpancreatectomy hemorrhage (OR 3.73, 95%CI 1.13-12.35, p = 0.031), grade B/C postoperative pancreatic fistula (OR 4.29, 95%CI 1.25-14.72, p = 0.038), and advanced age (OR 4.00, 95%CI 1.12-14.03, p = 0.033) were independent risk factors for in-hospital mortality in multivariable analysis. Median survival was 29 months, 5-year survival 27%. Positive resection margin (HR 2.07, 95%CI 1.29-3.33, p = 0.003), high tumor grade (HR 1.71, 95%CI 1.13-2.58, p = 0.010), lymph node (HR 1.68, 95%CI 1.13-2.51, p = 0.011), and distant metastases (HR 2.70, 95%CI 1.21-5.58, p = 0.014), as well as severe non-fatal postoperative complications (HR 1.64, 95%CI 1.04-2.58, p = 0.033) were independent negative prognostic factors for survival in multivariable analysis. CONCLUSION: Distant metastases and positive resection margin are the strongest negative prognostic factors for survival after pancreatoduodenectomy for distal bile duct carcinoma; thus, surgery with curative intent is only warranted in patients with local disease, where R0 resection is feasible.","Source":"PubMed","category":"HUMAN","training_data":"Survival outcome and prognostic factors after pancreatoduodenectomy for distal bile duct carcinoma: a retrospective multicenter study PURPOSE: Pancreatoduodenectomy is the most common operative procedure performed for distal bile duct carcinoma. Data on outcome after surgery for this rare malignancy is scarce, especially from western countries. The purpose of this study is to explore the prognostic factors and outcome after pancreatoduodenectomy for distal bile duct carcinoma. METHODS: Patients receiving pancreatoduodenectomy for distal bile duct carcinoma were identified from institutional databases of five German and one Russian academic centers for pancreatic surgery. Univariable and multivariable general linear model, Kaplan-Meier method, and Cox regression were used to identify prognostic factors for postoperative mortality and overall survival. RESULTS: N = 228 patients operated from 1994 to 2015 were included. Reoperation (OR 5.38, 95%CI 1.51-19.22, p = 0.010), grade B/C postpancreatectomy hemorrhage (OR 3.73, 95%CI 1.13-12.35, p = 0.031), grade B/C postoperative pancreatic fistula (OR 4.29, 95%CI 1.25-14.72, p = 0.038), and advanced age (OR 4.00, 95%CI 1.12-14.03, p = 0.033) were independent risk factors for in-hospital mortality in multivariable analysis. Median survival was 29 months, 5-year survival 27%. Positive resection margin (HR 2.07, 95%CI 1.29-3.33, p = 0.003), high tumor grade (HR 1.71, 95%CI 1.13-2.58, p = 0.010), lymph node (HR 1.68, 95%CI 1.13-2.51, p = 0.011), and distant metastases (HR 2.70, 95%CI 1.21-5.58, p = 0.014), as well as severe non-fatal postoperative complications (HR 1.64, 95%CI 1.04-2.58, p = 0.033) were independent negative prognostic factors for survival in multivariable analysis. CONCLUSION: Distant metastases and positive resection margin are the strongest negative prognostic factors for survival after pancreatoduodenectomy for distal bile duct carcinoma; thus, surgery with curative intent is only warranted in patients with local disease, where R0 resection is feasible. PubMed","prediction_labels":"HUMAN"},{"cleaned":"gallbladder cancer netherlands changes incidence treatment survival last two decades background gallbladder cancer gc relative rare neoplasm examine recent trends gc unselected patient population western world cancer registration data gc netherlands analysed methods trends incidence treatment en survival according gender age stage disease period diagnosis studied 1989 2008 3917 patients results age standardized incidence rate asr gc netherlands decreased signi cantly 1989 2008 males females incidence rate gc decreased signi cantly males age group 60 74 years well age group 75 years signi cant decrease males younger 60 years females age groups 45 59 60 74 75 years signi cantly decrease incidence rate gc signi cant decrease gc incidence females younger 44 years resection rate remained stable 100 tumour lymph node metastasis classi cation tnm stage treatment patterns tnm stage ii iii iv changed 1989 patients tnm stage ii often treated surgery decreased study period shifted receiving chemotherapy radiation treatment 2008 often changes treatment pattern seen patients stage iii iv relative overall survival rates change last 20 years 5 year survival rate 11 13 p 0 601 treatment speci c survival change signi cantly 1 5 year survival rate patients receiving surgery increased 45 19 1989 1992 56 26 2003 2008 conclusion incidence gallbladder cancer netherlands decreased treatment patterns gallbladder cancer changed patients stage ii iii iv decrease surgical treatment increase chemotherapy radiation treatment relative overall survival remained stable 5 year survival rate 11 13 google scholar","probabilities":0.9799733,"Title":"Gallbladder Cancer In The Netherlands: Changes In Incidence Treatment And Survival During The Last Two Decades","Abstract":"Background: Gallbladder cancer (GC) is a relative rare neoplasm. To examine recent trends of GC in an unselected patient population in the Western world, cancer registration data of GC in the Netherlands were analysed. Methods: Trends in incidence, treatment en survival, according to gender, age, stage of disease and period of diagnosis were studied between 1989 and 2008 in 3917 patients. Results: Age-standardized incidence rate (ASR) of GC in the Netherlands decreased significantly from 1989–2008 for both males and females. Incidence rate of GC decreased significantly in males from age group 60–74 years as well as age group ≥75 years, there was no significant decrease in males younger than 60 years. In females the age groups from 45–59, 60–74 and ≥75 years had a significantly decrease of incidence rate of GC, there was no significant decrease of GC incidence of females younger than 44 years. Resection rate remained stable on 100% for Tumour Lymph Node Metastasis classification (TNM) stage I, while treatment patterns for TNM stage II, III and IV changed. In 1989 patients with TNM stage II were often treated with surgery, which decreased during the study period and shifted to receiving chemotherapy and/or radiation or no treatment in 2008 more often. The same changes in treatment pattern were seen in patients in stage III and IV. The relative overall survival rates did not change during the last 20 years with a 5 year-survival rate of 11–13% (p=0.601). Treatment specific survival did not change significantly, the 1- and 5-year survival rate for patients receiving surgery increased from 45% and 19% in 1989–1992 to 56% and 26% in 2003–2008. Conclusion: The incidence of gallbladder cancer in the Netherlands decreased. Treatment patterns of gallbladder cancer changed; patients in stage II, III and IV had a decrease of surgical treatment and an increase of chemotherapy and/or radiation or no treatment. The relative overall survival remained stable with a 5 year-survival rate of 11–13%","Source":"Google Scholar","category":"HUMAN","training_data":"Gallbladder Cancer In The Netherlands: Changes In Incidence Treatment And Survival During The Last Two Decades Background: Gallbladder cancer (GC) is a relative rare neoplasm. To examine recent trends of GC in an unselected patient population in the Western world, cancer registration data of GC in the Netherlands were analysed. Methods: Trends in incidence, treatment en survival, according to gender, age, stage of disease and period of diagnosis were studied between 1989 and 2008 in 3917 patients. Results: Age-standardized incidence rate (ASR) of GC in the Netherlands decreased significantly from 1989–2008 for both males and females. Incidence rate of GC decreased significantly in males from age group 60–74 years as well as age group ≥75 years, there was no significant decrease in males younger than 60 years. In females the age groups from 45–59, 60–74 and ≥75 years had a significantly decrease of incidence rate of GC, there was no significant decrease of GC incidence of females younger than 44 years. Resection rate remained stable on 100% for Tumour Lymph Node Metastasis classification (TNM) stage I, while treatment patterns for TNM stage II, III and IV changed. In 1989 patients with TNM stage II were often treated with surgery, which decreased during the study period and shifted to receiving chemotherapy and/or radiation or no treatment in 2008 more often. The same changes in treatment pattern were seen in patients in stage III and IV. The relative overall survival rates did not change during the last 20 years with a 5 year-survival rate of 11–13% (p=0.601). Treatment specific survival did not change significantly, the 1- and 5-year survival rate for patients receiving surgery increased from 45% and 19% in 1989–1992 to 56% and 26% in 2003–2008. Conclusion: The incidence of gallbladder cancer in the Netherlands decreased. Treatment patterns of gallbladder cancer changed; patients in stage II, III and IV had a decrease of surgical treatment and an increase of chemotherapy and/or radiation or no treatment. The relative overall survival remained stable with a 5 year-survival rate of 11–13% Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"comparison trends mortality primary liver cancer intrahepatic cholangiocarcinoma europe background update compare mortality primary liver cancer plc intrahepatic cholangiocarcinoma icc europe 1990 2010 materials methods used data world health organization compute age standardized world population mortality rates used joinpoint analysis identify substantial changes results 2002 2007 plc rates european union eu declined 3 9 3 6 100 000 men around 2007 highest male rates france 6 2 100 000 spain 4 9 italy 4 0 lowest ones sweden 1 1 netherlands 1 2 uk 1 8 women mortality lower 0 8 100 000 2007 eu showed favourable trends decline 2 per year last two decades compared 0 4 men eu contrast eu mortality icc increased around 9 sexes 1990 2008 reaching rates 1 1 100 000 men 0 75 100 000 women highest rates uk germany france 1 2 1 5 100 000 men 0 8 1 1 100 000 women conclusions plc mortality become uniform across europe recent years overall decline contrast icc mortality substantially increased europe stn","probabilities":0.9799733,"Title":"A Comparison Of Trends In Mortality From Primary Liver Cancer And Intrahepatic Cholangiocarcinoma In Europe","Abstract":"Background: To update and compare mortality from primary liver cancer (PLC) and intrahepatic cholangiocarcinoma (ICC) in Europe in 1990-2010. \r\n\r\n Materials and methods: We used data from the World Health Organization (WHO) to compute age-standardized (world population) mortality rates, and used joinpoint analysis to identify substantial changes. \r\n\r\n Results: Between 2002 and 2007, PLC rates in the European Union (EU) declined from 3.9 to 3.6/100,000 men. Around 2007, the highest male rates were in France (6.2/100,000), Spain (4.9), and Italy (4.0), while the lowest ones were in Sweden (1.1), the Netherlands (1.2), and the UK (1.8). In women, mortality was lower (0.8/100,000 in 2007 in the EU), and showed more favourable trends, with a decline of over 2% per year over the last two decades as compared with 0.4% in men, in the EU. In contrast, the EU mortality from ICC increased by around 9% in both sexes from 1990 to 2008, reaching rates of 1.1/100,000 men and 0.75/100,000 women. The highest rates were in UK, Germany, and France (1.2-1.5/100,000 men, 0.8-1.1/100,000 women). \r\n\r\n Conclusions: PLC mortality has become more uniform across Europe over recent years, with an overall decline; in contrast, ICC mortality has substantially increased in most Europe.","Source":"STN","category":"HUMAN","training_data":"A Comparison Of Trends In Mortality From Primary Liver Cancer And Intrahepatic Cholangiocarcinoma In Europe Background: To update and compare mortality from primary liver cancer (PLC) and intrahepatic cholangiocarcinoma (ICC) in Europe in 1990-2010. \r\n\r\n Materials and methods: We used data from the World Health Organization (WHO) to compute age-standardized (world population) mortality rates, and used joinpoint analysis to identify substantial changes. \r\n\r\n Results: Between 2002 and 2007, PLC rates in the European Union (EU) declined from 3.9 to 3.6/100,000 men. Around 2007, the highest male rates were in France (6.2/100,000), Spain (4.9), and Italy (4.0), while the lowest ones were in Sweden (1.1), the Netherlands (1.2), and the UK (1.8). In women, mortality was lower (0.8/100,000 in 2007 in the EU), and showed more favourable trends, with a decline of over 2% per year over the last two decades as compared with 0.4% in men, in the EU. In contrast, the EU mortality from ICC increased by around 9% in both sexes from 1990 to 2008, reaching rates of 1.1/100,000 men and 0.75/100,000 women. The highest rates were in UK, Germany, and France (1.2-1.5/100,000 men, 0.8-1.1/100,000 women). \r\n\r\n Conclusions: PLC mortality has become more uniform across Europe over recent years, with an overall decline; in contrast, ICC mortality has substantially increased in most Europe. STN","prediction_labels":"HUMAN"},{"cleaned":"cross sectional study cardiorespiratory fitness gallbladder disease purpose determine association different levels cardiorespiratory fitness crf objective indicator habitual physical activity gallbladder disease methods aerobics center longitudinal study acls database 41 528 men 13 206 women aged 20 90 years body mass index 18 5 without history cardiovascular disease cancer received preventive examination cooper clinic dallas texas 1970 2003 crf quantified maximal metabolic equivalents classified low moderate high based traditional acls cut points gallbladder disease defined physician diagnosed gallbladder disease results compared low crf adjusted odds ratios 95 confidence intervals gallbladder disease moderate high crf 0 74 0 55 0 99 0 59 0 42 0 82 respectively adjusted potential confounders one metabolic equivalent increment crf associated 10 lower odds gallbladder disease participants p trend 001 13 lower women p trend 001 8 lower men p trend 08 association consistent across age history diabetes mellitus physical inactivity subgroups conclusions crf inversely related prevalence gallbladder disease among relatively healthy men women acls cohort pubmed","probabilities":0.9799733,"Title":"A cross-sectional study of cardiorespiratory fitness and gallbladder disease","Abstract":"PURPOSE: To determine the association of different levels of cardiorespiratory fitness (CRF), an objective indicator of habitual physical activity, with gallbladder disease. METHODS: In the Aerobics Center Longitudinal Study (ACLS) database, 41,528 men and 13,206 women aged 20-90 years, with body mass index of 18.5 or more and without history of cardiovascular disease and cancer, received a preventive examination at the Cooper Clinic in Dallas, Texas, between 1970 and 2003. CRF was quantified as maximal metabolic equivalents and classified as low, moderate, and high based on traditional ACLS cut points. Gallbladder disease was defined as physician-diagnosed gallbladder disease. RESULTS: When compared with low CRF, adjusted odds ratios and 95% confidence intervals for gallbladder disease for those with moderate and high CRF were 0.74 (0.55-0.99) and 0.59 (0.42-0.82), respectively when adjusted for all the potential confounders. Each one metabolic equivalent increment of CRF was associated with 10% lower odds of gallbladder disease in all participants (P for trend <.001), 13% lower in women (P for trend <.001), and 8% lower in men (P for trend = .08). The association was consistent across age, history of diabetes mellitus, and physical inactivity subgroups. CONCLUSIONS: CRF is inversely related to the prevalence of gallbladder disease among relatively healthy men and women in the ACLS cohort.","Source":"PubMed","category":"HUMAN","training_data":"A cross-sectional study of cardiorespiratory fitness and gallbladder disease PURPOSE: To determine the association of different levels of cardiorespiratory fitness (CRF), an objective indicator of habitual physical activity, with gallbladder disease. METHODS: In the Aerobics Center Longitudinal Study (ACLS) database, 41,528 men and 13,206 women aged 20-90 years, with body mass index of 18.5 or more and without history of cardiovascular disease and cancer, received a preventive examination at the Cooper Clinic in Dallas, Texas, between 1970 and 2003. CRF was quantified as maximal metabolic equivalents and classified as low, moderate, and high based on traditional ACLS cut points. Gallbladder disease was defined as physician-diagnosed gallbladder disease. RESULTS: When compared with low CRF, adjusted odds ratios and 95% confidence intervals for gallbladder disease for those with moderate and high CRF were 0.74 (0.55-0.99) and 0.59 (0.42-0.82), respectively when adjusted for all the potential confounders. Each one metabolic equivalent increment of CRF was associated with 10% lower odds of gallbladder disease in all participants (P for trend <.001), 13% lower in women (P for trend <.001), and 8% lower in men (P for trend = .08). The association was consistent across age, history of diabetes mellitus, and physical inactivity subgroups. CONCLUSIONS: CRF is inversely related to the prevalence of gallbladder disease among relatively healthy men and women in the ACLS cohort. PubMed","prediction_labels":"HUMAN"},{"cleaned":"reappraisal prognostic impact tumor suvmax 18 f fdg pet ct intrahepatic cholangiocarcinoma background previously reported tumor standardized uptake value suvmax 18f fluorodeoxyglucose positron emission tomography computed tomography pet ct potential predictor patients undergoing surgery intrahepatic cholangiocarcinoma icc however prognostic value suvmax era multidisciplinary strategy remained unclear aim study reappraise prognostic value tumor suvmax patients undergoing surgery icc methods data 82 consecutive icc patients underwent 18f fdg pet ct subsequent surgery 2006 2017 retrieved prospectively maintained institutional database adjuvant strategy administrated study period center results tumor suvmax associated tumor size p 0 002 tumor number p 0 005 associated n stage classified american joint committee cancer classification system tumor factors according tumor suvmax cut values 8 0 based minimum p value approach actuarial 5 year overall survival os rates patients undergoing upfront surgery icc significantly stratified 54 7 versus 26 0 low vs high tumor suvmax group p 0 008 actuarial 3 year disease free survival dfs rates also significantly stratified 41 0 versus 18 3 p 0 001 multivariate cox regression analyses revealed tumor suvmax retained significance os p 0 039 well dfs p 0 001 conclusion even era multidisciplinary strategy high tumor suvmax still represents poor prognosis patients undergoing surgery icc patients therefore probably required effective strategies stn","probabilities":0.9799733,"Title":"Reappraisal Of Prognostic Impact Of Tumor Suvmax By (18)F-Fdg-Pet/Ct In Intrahepatic Cholangiocarcinoma","Abstract":"Background: We previously reported that tumor standardized uptake value (SUVmax) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) was a potential predictor in patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of SUVmax in the era of multidisciplinary strategy has remained unclear. The aim of this study was to reappraise the prognostic value of tumor SUVmax in patients undergoing surgery for ICC. \r\n\r\n Methods: Data from 82 consecutive ICC patients, who underwent 18F-FDG-PET/CT and subsequent surgery between 2006 and 2017, were retrieved from a prospectively maintained institutional database. Adjuvant strategy was administrated during this study period in our center. \r\n\r\n Results: Tumor SUVmax was associated with tumor size (p = 0.002) and tumor number (p = 0.005), but not associated with T and N stage classified by American Joint Committee on Cancer-classification system, and other tumor factors. According to the tumor SUVmax cut-off values of 8.0 based on the minimum p value approach, actuarial 5-year overall survival (OS) rates in patients undergoing upfront surgery for ICC were significantly stratified at 54.7% versus 26.0% (low vs. high tumor SUVmax group, p = 0.008). The actuarial 3-year disease-free survival (DFS) rates were also significantly stratified at 41.0% versus 18.3% (p < 0.001). Multivariate Cox regression analyses revealed that tumor SUVmax retained its significance on OS (p = 0.039) as well as DFS (p < 0.001). \r\n\r\n Conclusion: Even in the era of multidisciplinary strategy, high tumor SUVmax still represents poor prognosis in patients undergoing surgery for ICC. These patients, therefore, would probably be required more effective strategies.","Source":"STN","category":"HUMAN","training_data":"Reappraisal Of Prognostic Impact Of Tumor Suvmax By (18)F-Fdg-Pet/Ct In Intrahepatic Cholangiocarcinoma Background: We previously reported that tumor standardized uptake value (SUVmax) by 18F-fluorodeoxyglucose-positron emission tomography/computed tomography (PET/CT) was a potential predictor in patients undergoing surgery for intrahepatic cholangiocarcinoma (ICC). However, the prognostic value of SUVmax in the era of multidisciplinary strategy has remained unclear. The aim of this study was to reappraise the prognostic value of tumor SUVmax in patients undergoing surgery for ICC. \r\n\r\n Methods: Data from 82 consecutive ICC patients, who underwent 18F-FDG-PET/CT and subsequent surgery between 2006 and 2017, were retrieved from a prospectively maintained institutional database. Adjuvant strategy was administrated during this study period in our center. \r\n\r\n Results: Tumor SUVmax was associated with tumor size (p = 0.002) and tumor number (p = 0.005), but not associated with T and N stage classified by American Joint Committee on Cancer-classification system, and other tumor factors. According to the tumor SUVmax cut-off values of 8.0 based on the minimum p value approach, actuarial 5-year overall survival (OS) rates in patients undergoing upfront surgery for ICC were significantly stratified at 54.7% versus 26.0% (low vs. high tumor SUVmax group, p = 0.008). The actuarial 3-year disease-free survival (DFS) rates were also significantly stratified at 41.0% versus 18.3% (p < 0.001). Multivariate Cox regression analyses revealed that tumor SUVmax retained its significance on OS (p = 0.039) as well as DFS (p < 0.001). \r\n\r\n Conclusion: Even in the era of multidisciplinary strategy, high tumor SUVmax still represents poor prognosis in patients undergoing surgery for ICC. These patients, therefore, would probably be required more effective strategies. STN","prediction_labels":"HUMAN"},{"cleaned":"novel predictive equation potential diagnosis cholangiocarcinoma cholangiocarcinoma cca second common primary liver cancer difficulties diagnosis limit successful treatment cca present histological investigation standard diagnosis cca however poor defined tumor tissues definitively diagnosed general histopathology molecular signatures define molecular phenotypes related diagnosis prognosis treatment outcome cca second common cancer found hepatocellularcarcinoma hcc aim study develop predictive model differentiates cca hcc normal liver tissues house pcr array containing 176 putative cca marker genes tested training set tissues 20 cca 10 hcc cases molecular signature cca revealed prominent expression genes involved cell adhesion cell movement whereas hcc showed elevated expression genes related cell proliferation differentiation metabolisms total 69 genes differentially expressed cca hcc optimized statistically formulate diagnostic equation distinguished cca cases hcc cases finally four gene diagnostic equation cldn4 hoxb7 tmsb4 ttr formulated successfully validated using real time pcr independent testing set 68 cca samples 77 non cca controls discrimination analysis showed combination genes used diagnostic marker cca better diagnostic parameters high sensitivity specificity using single gene marker usual serum markers ca19 9 cea new combination marker may help physicians identify cca liver tissues histopathology uncertain stn","probabilities":0.9467213,"Title":"A Novel Predictive Equation For Potential Diagnosis Of Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is the second most common-primary liver cancer. The difficulties in diagnosis limit successful treatment of CCA. At present, histological investigation is the standard diagnosis for CCA. However, there are some poor-defined tumor tissues which cannot be definitively diagnosed by general histopathology. As molecular signatures can define molecular phenotypes related to diagnosis, prognosis, or treatment outcome, and CCA is the second most common cancer found after hepatocellularcarcinoma (HCC), the aim of this study was to develop a predictive model which differentiates CCA from HCC and normal liver tissues. An in-house PCR array containing 176 putative CCA marker genes was tested with the training set tissues of 20 CCA and 10 HCC cases. The molecular signature of CCA revealed the prominent expression of genes involved in cell adhesion and cell movement, whereas HCC showed elevated expression of genes related to cell proliferation/differentiation and metabolisms. A total of 69 genes differentially expressed in CCA and HCC were optimized statistically to formulate a diagnostic equation which distinguished CCA cases from HCC cases. Finally, a four-gene diagnostic equation (CLDN4, HOXB7, TMSB4 and TTR) was formulated and then successfully validated using real-time PCR in an independent testing set of 68 CCA samples and 77 non-CCA controls. Discrimination analysis showed that a combination of these genes could be used as a diagnostic marker for CCA with better diagnostic parameters with high sensitivity and specificity than using a single gene marker or the usual serum markers (CA19-9 and CEA). This new combination marker may help physicians to identify CCA in liver tissues when the histopathology is uncertain.","Source":"STN","category":"ANIMAL","training_data":"A Novel Predictive Equation For Potential Diagnosis Of Cholangiocarcinoma Cholangiocarcinoma (CCA) is the second most common-primary liver cancer. The difficulties in diagnosis limit successful treatment of CCA. At present, histological investigation is the standard diagnosis for CCA. However, there are some poor-defined tumor tissues which cannot be definitively diagnosed by general histopathology. As molecular signatures can define molecular phenotypes related to diagnosis, prognosis, or treatment outcome, and CCA is the second most common cancer found after hepatocellularcarcinoma (HCC), the aim of this study was to develop a predictive model which differentiates CCA from HCC and normal liver tissues. An in-house PCR array containing 176 putative CCA marker genes was tested with the training set tissues of 20 CCA and 10 HCC cases. The molecular signature of CCA revealed the prominent expression of genes involved in cell adhesion and cell movement, whereas HCC showed elevated expression of genes related to cell proliferation/differentiation and metabolisms. A total of 69 genes differentially expressed in CCA and HCC were optimized statistically to formulate a diagnostic equation which distinguished CCA cases from HCC cases. Finally, a four-gene diagnostic equation (CLDN4, HOXB7, TMSB4 and TTR) was formulated and then successfully validated using real-time PCR in an independent testing set of 68 CCA samples and 77 non-CCA controls. Discrimination analysis showed that a combination of these genes could be used as a diagnostic marker for CCA with better diagnostic parameters with high sensitivity and specificity than using a single gene marker or the usual serum markers (CA19-9 and CEA). This new combination marker may help physicians to identify CCA in liver tissues when the histopathology is uncertain. STN","prediction_labels":"ANIMAL"},{"cleaned":"prognostic implications slit robo1 expression gallbladder cancer slit secretory glycoprotein receptor roundabout robo expressed several types cancer implicated tumor angiogenesis purpose study determine prognostic implications slit robo1 expression association clinicopathologic characteristics gallbladder cancer retrospective analysis 109 consecutive patients underwent primary gallbladder cancer resection conducted univariate multivariate models used analyze effect clinicopathologic factors survival expression slit robo1 evaluated immunohistochemistry association clinicopathologic characteristics analyzed using mean testing multivariate linear regression analysis also applied investigate independent predictors robo1 expression seventy five patients included post resection survival analysis 1 year 3 year overall survival rates 60 40 respectively univariate analysis revealed pn classification pt classification pm classification liver involvement perineural invasion tnm staging nevin staging microscopic resection margins affect prognosis multivariate analysis confirmed pn classification liver involvement perineural invasion independent prognostic factors mean tests 109 cases mean difference slit immunoreactivity significant according presence gallstones p 0 003 liver involvement p 0 005 mean difference robo1 immunoreactivity significant according liver involvement p 0 001 tnm staging p 0 001 nevin staging p 0 001 multivariate analysis robo1 immunoreactivity showed slit immunoreactivity tnm stage adjusted r 2 0 203 slit immunoreactivity nevin stage adjusted r 2 0 195 independent predictors robo1 expression pn classification liver involvement perineural invasion pathologic stage significant prognostic factors gallbladder cancer survival slit expression associated cholelithiasis liver involvement robo1 expression associated liver involvement pathologic stage addition slit expression pathologic stage predict robo1 expression independently pubmed","probabilities":0.9799733,"Title":"Prognostic implications of SLIT and ROBO1 expression in gallbladder cancer","Abstract":"SLIT, a secretory glycoprotein, and its receptor roundabout (ROBO) are expressed in several types of cancer and have been implicated in tumor angiogenesis. The purpose of this study was to determine the prognostic implications of SLIT and ROBO1 expression and their association with clinicopathologic characteristics in gallbladder cancer. A retrospective analysis of 109 consecutive patients who underwent primary gallbladder cancer resection was conducted. Univariate and multivariate models were used to analyze the effect of clinicopathologic factors on survival. Expression of SLIT and ROBO1 was evaluated by immunohistochemistry, and their association with clinicopathologic characteristics was analyzed using mean testing. Multivariate linear regression analysis was also applied to investigate the independent predictors of ROBO1 expression. Seventy-five patients were included in the post-resection survival analysis, with 1-year and 3-year overall survival rates of 60 and 40 %, respectively. Univariate analysis revealed that pN classification, pT classification, pM classification, liver involvement, perineural invasion, TNM staging, Nevin staging, and microscopic resection margins affect prognosis. Multivariate analysis confirmed that pN classification, liver involvement, and perineural invasion are independent prognostic factors. In the mean tests of 109 cases, the mean difference of SLIT immunoreactivity was significant according to the presence of gallstones (P = 0.003) and liver involvement (P = 0.005), while the mean difference of ROBO1 immunoreactivity was significant according to liver involvement (P < 0.001), TNM staging (P < 0.001), and Nevin staging (P < 0.001). Multivariate analysis of ROBO1 immunoreactivity showed that SLIT immunoreactivity and TNM stage (adjusted R (2) = 0.203) or SLIT immunoreactivity and Nevin stage (adjusted R (2) = 0.195) were independent predictors of ROBO1 expression. pN classification, liver involvement, perineural invasion, and pathologic stage are significant prognostic factors for gallbladder cancer survival. SLIT expression is associated with cholelithiasis and liver involvement, and ROBO1 expression is associated with liver involvement and pathologic stage. In addition, SLIT expression and pathologic stage predict ROBO1 expression independently.","Source":"PubMed","category":"HUMAN","training_data":"Prognostic implications of SLIT and ROBO1 expression in gallbladder cancer SLIT, a secretory glycoprotein, and its receptor roundabout (ROBO) are expressed in several types of cancer and have been implicated in tumor angiogenesis. The purpose of this study was to determine the prognostic implications of SLIT and ROBO1 expression and their association with clinicopathologic characteristics in gallbladder cancer. A retrospective analysis of 109 consecutive patients who underwent primary gallbladder cancer resection was conducted. Univariate and multivariate models were used to analyze the effect of clinicopathologic factors on survival. Expression of SLIT and ROBO1 was evaluated by immunohistochemistry, and their association with clinicopathologic characteristics was analyzed using mean testing. Multivariate linear regression analysis was also applied to investigate the independent predictors of ROBO1 expression. Seventy-five patients were included in the post-resection survival analysis, with 1-year and 3-year overall survival rates of 60 and 40 %, respectively. Univariate analysis revealed that pN classification, pT classification, pM classification, liver involvement, perineural invasion, TNM staging, Nevin staging, and microscopic resection margins affect prognosis. Multivariate analysis confirmed that pN classification, liver involvement, and perineural invasion are independent prognostic factors. In the mean tests of 109 cases, the mean difference of SLIT immunoreactivity was significant according to the presence of gallstones (P = 0.003) and liver involvement (P = 0.005), while the mean difference of ROBO1 immunoreactivity was significant according to liver involvement (P < 0.001), TNM staging (P < 0.001), and Nevin staging (P < 0.001). Multivariate analysis of ROBO1 immunoreactivity showed that SLIT immunoreactivity and TNM stage (adjusted R (2) = 0.203) or SLIT immunoreactivity and Nevin stage (adjusted R (2) = 0.195) were independent predictors of ROBO1 expression. pN classification, liver involvement, perineural invasion, and pathologic stage are significant prognostic factors for gallbladder cancer survival. SLIT expression is associated with cholelithiasis and liver involvement, and ROBO1 expression is associated with liver involvement and pathologic stage. In addition, SLIT expression and pathologic stage predict ROBO1 expression independently. PubMed","prediction_labels":"HUMAN"},{"cleaned":"toward personalized treatment advanced biliary tract cancers biliary tract cancers btc relatively rare heterogeneous group four five anatomically distinct cancers whose prognosis poor even setting attempted curative resection curative resection much less common locally advanced unresectable overt metastatic disease presentation standard chemotherapy options generally palliative advanced btc abtc recently combination gemcitabine cisplatin emerged standard care providing median overall survival approximately one year movement toward molecularly based personalized cancer therapy occurred recent years including abtc number pathways emerging putative therapeutic targets review briefly summarize epidemiology etiology general prognosis btc discuss data supporting current standard cytotoxic treatments abtc proceed focus molecular features heterogeneous set diseases finally review strategies potentially improve ability individualize therapy ultimately clinical outcomes future pubmed","probabilities":0.9799733,"Title":"Toward personalized treatment of advanced biliary tract cancers","Abstract":"Biliary tract cancers (BTC) are a relatively rare heterogeneous group of four to five anatomically distinct cancers whose prognosis is poor, even in the setting of attempted curative resection. Curative resection, in itself, is much less common than locally advanced unresectable and/or overt metastatic disease at presentation. Standard chemotherapy options are generally palliative for advanced BTC (aBTC), and recently the combination of gemcitabine with cisplatin has emerged as the standard-of-care providing a median overall survival of approximately one year. A movement toward molecularly based personalized cancer therapy has occurred in recent years, including for aBTC, with a number of pathways emerging as putative therapeutic targets. This review will briefly summarize the epidemiology, etiology, and general prognosis of BTC, then discuss the data supporting current standard cytotoxic treatments of aBTC, and proceed to focus on the molecular features of this heterogeneous set of diseases. Finally, we review strategies which will potentially improve our ability to individualize therapy and, ultimately, clinical outcomes in the future.","Source":"PubMed","category":"HUMAN","training_data":"Toward personalized treatment of advanced biliary tract cancers Biliary tract cancers (BTC) are a relatively rare heterogeneous group of four to five anatomically distinct cancers whose prognosis is poor, even in the setting of attempted curative resection. Curative resection, in itself, is much less common than locally advanced unresectable and/or overt metastatic disease at presentation. Standard chemotherapy options are generally palliative for advanced BTC (aBTC), and recently the combination of gemcitabine with cisplatin has emerged as the standard-of-care providing a median overall survival of approximately one year. A movement toward molecularly based personalized cancer therapy has occurred in recent years, including for aBTC, with a number of pathways emerging as putative therapeutic targets. This review will briefly summarize the epidemiology, etiology, and general prognosis of BTC, then discuss the data supporting current standard cytotoxic treatments of aBTC, and proceed to focus on the molecular features of this heterogeneous set of diseases. Finally, we review strategies which will potentially improve our ability to individualize therapy and, ultimately, clinical outcomes in the future. PubMed","prediction_labels":"HUMAN"},{"cleaned":"single nucleotide polymorphism ezh2 predicts overall survival rate patients cholangiocarcinoma cholangiocarcinoma cca deadly disease arising malignant transformation cholangiocytes enhancer zeste homolog 2 ezh2 overexpressed poorly differentiated cca functional single nucleotide polymorphisms snps gene may affect role ezh2 cholangiocarcinogenesis chemoresistance aim current study evaluate correlation ezh2 snps clinical outcome using promo3 0 genecard microsniper 4 ezh2 snps functional relevance cca selected silico snps studied genomic dna extracted blood samples 75 patients advanced cca treated epirubicin cisplatin xeloda ecx regimen snp genotyping performed specific pcr assays rs887569 tt genotype correlated significantly longer overall survival os tt vs ct cc p 0 026 moreover tt genotype revealed trend toward significant association reduced risk mortality hr 0 59 95 ci 0 33 1 05 p 0 075 multivariate analysis results support future studies role rs887569 ezh2 snp possible predictive marker os advanced cca patients stn","probabilities":0.5555556,"Title":"A Single Nucleotide Polymorphism In Ezh2 Predicts Overall Survival Rate In Patients With Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a deadly disease arising from the malignant transformation of cholangiocytes. Enhancer of zeste homolog 2 (EZH2) is overexpressed in poorly differentiated CCA. Functional single nucleotide polymorphisms (SNPs) in this gene may affect the role of EZH2 in cholangiocarcinogenesis and chemoresistance. The aim of the current study was to evaluate the correlation between EZH2 SNPs and clinical outcome. Using PROMO3.0, GeneCard and MicroSNiper, 4 EZH2 SNPs with functional relevance in CCA were selected in silico. These SNPs were studied in genomic DNA extracted from the blood samples of 75 patients with advanced CCA, who were treated with epirubicin-cisplatin-xeloda (ECX regimen). SNP genotyping was performed with specific PCR assays. The rs887569 TT genotype was correlated with a significantly longer overall survival (OS; TT vs. CT-CC, P=0.026). Moreover, the TT genotype revealed a trend toward a significant association with a reduced risk of mortality (HR, 0.59; 95% CI, 0.33-1.05; P=0.075), by multivariate analysis. These results support future studies on the role of rs887569 EZH2 SNP as a possible predictive marker of OS in advanced CCA patients.","Source":"STN","category":"HUMAN","training_data":"A Single Nucleotide Polymorphism In Ezh2 Predicts Overall Survival Rate In Patients With Cholangiocarcinoma Cholangiocarcinoma (CCA) is a deadly disease arising from the malignant transformation of cholangiocytes. Enhancer of zeste homolog 2 (EZH2) is overexpressed in poorly differentiated CCA. Functional single nucleotide polymorphisms (SNPs) in this gene may affect the role of EZH2 in cholangiocarcinogenesis and chemoresistance. The aim of the current study was to evaluate the correlation between EZH2 SNPs and clinical outcome. Using PROMO3.0, GeneCard and MicroSNiper, 4 EZH2 SNPs with functional relevance in CCA were selected in silico. These SNPs were studied in genomic DNA extracted from the blood samples of 75 patients with advanced CCA, who were treated with epirubicin-cisplatin-xeloda (ECX regimen). SNP genotyping was performed with specific PCR assays. The rs887569 TT genotype was correlated with a significantly longer overall survival (OS; TT vs. CT-CC, P=0.026). Moreover, the TT genotype revealed a trend toward a significant association with a reduced risk of mortality (HR, 0.59; 95% CI, 0.33-1.05; P=0.075), by multivariate analysis. These results support future studies on the role of rs887569 EZH2 SNP as a possible predictive marker of OS in advanced CCA patients. STN","prediction_labels":"ANIMAL"},{"cleaned":"expression cd24 cholangiocarcinoma cells associated disease progression reduced patient survival cholangiocarcinoma frequently found invade local tissues metastasize distal organs investigated expression cd24 cholangiocarcinoma samples prognostic significance addition cellular function cd24 studied rmcca1 cholangiocarcinoma cell line high cd24 expression significantly correlated lymph node metastasis positive surgical margins cholangiocarcinoma patients univariate multivariate analyses demonstrated cd24 expression significantly associated overall survival patients p 0 007 p 0 040 respectively vitro studies magnetic activated cell sorting macs system used isolate cd24 cd24 cell populations rmcca1 cells cd24 rmcca1 cells increased chemoresistance adhesion p 0 004 motility p 0 001 migration p 0 001 invasion p 0 001 capabilities compared cd24 cells matrix metalloproteinase mmp 7 significantly elevated cd24 rmcca1 cells p 0 01 found inhibition cd24 using sirna silencing significantly decreased invasive capacity rmcca1 cells clinical vitro studies suggest expression cd24 associated cholangiocarcinoma disease progression cd24 may thus serve new target directed molecular therapy cholangiocarcinoma stn","probabilities":0.9467213,"Title":"Expression Of Cd24 In Cholangiocarcinoma Cells Is Associated With Disease Progression And Reduced Patient Survival","Abstract":"Cholangiocarcinoma is frequently found to invade local tissues and metastasize to distal organs. We investigated the expression of CD24 in cholangiocarcinoma samples and its prognostic significance. In addition, the cellular function of CD24 was studied in the RMCCA1 cholangiocarcinoma cell line. High CD24 expression significantly correlated with lymph node metastasis and positive surgical margins in cholangiocarcinoma patients. Univariate and multivariate analyses further demonstrated that CD24 expression was significantly associated with the overall survival of these patients (p=0.007 and p=0.040, respectively). For in vitro studies, the magnetic-activated cell sorting (MACS) system was used to isolate CD24+ and CD24- cell populations from RMCCA1 cells. CD24+ RMCCA1 cells had increased chemoresistance, adhesion (p=0.004), motility (p<0.001), migration (p<0.001) and invasion (p<0.001) capabilities when compared to CD24- cells. The matrix metalloproteinase (MMP)-7 was significantly elevated in CD24+ RMCCA1 cells (p=0.01). We found that inhibition of CD24 using siRNA silencing significantly decreased the invasive capacity of RMCCA1 cells. Both clinical and in vitro studies suggest that expression of CD24 is associated with cholangiocarcinoma disease progression. CD24 may thus serve as a new target for directed molecular therapy of cholangiocarcinoma.","Source":"STN","category":"ANIMAL","training_data":"Expression Of Cd24 In Cholangiocarcinoma Cells Is Associated With Disease Progression And Reduced Patient Survival Cholangiocarcinoma is frequently found to invade local tissues and metastasize to distal organs. We investigated the expression of CD24 in cholangiocarcinoma samples and its prognostic significance. In addition, the cellular function of CD24 was studied in the RMCCA1 cholangiocarcinoma cell line. High CD24 expression significantly correlated with lymph node metastasis and positive surgical margins in cholangiocarcinoma patients. Univariate and multivariate analyses further demonstrated that CD24 expression was significantly associated with the overall survival of these patients (p=0.007 and p=0.040, respectively). For in vitro studies, the magnetic-activated cell sorting (MACS) system was used to isolate CD24+ and CD24- cell populations from RMCCA1 cells. CD24+ RMCCA1 cells had increased chemoresistance, adhesion (p=0.004), motility (p<0.001), migration (p<0.001) and invasion (p<0.001) capabilities when compared to CD24- cells. The matrix metalloproteinase (MMP)-7 was significantly elevated in CD24+ RMCCA1 cells (p=0.01). We found that inhibition of CD24 using siRNA silencing significantly decreased the invasive capacity of RMCCA1 cells. Both clinical and in vitro studies suggest that expression of CD24 is associated with cholangiocarcinoma disease progression. CD24 may thus serve as a new target for directed molecular therapy of cholangiocarcinoma. STN","prediction_labels":"ANIMAL"},{"cleaned":"vitro vivo antitumor activity tiliacorinine human cholangiocarcinoma cholangiocarcinoma cca fatal cancer poor prognosis less 10 cca patients offered surgical cure conventional chemotherapy results unfavorable outcomes present plant derived compounds gaining interest potential cancer therapeutics particularly treatment refractory cancers study antitumor activity tiliacorinine major alkaloid isolated tropical plant cca first demonstrated antiproliferative effects tiliacorinine human cca cell lines investigated using srb assays acridine orange ethidium bromide staining flow cytometric analysis dna laddering assays used apoptotic determination apoptosis related proteins verified western blotting antitumor activity tiliacorinine vivo demonstrated cca xenografted mice tiliacorinine significantly inhibited proliferation human cca cell lines ic50 4 5 7 m inducing apoptosis caspase activation regulation bax regulation bclxl xiap tiliacorinine considerably reduced tumor growth cca xenografted mice results demonstrated antitumor effects tiliacorinine human cca vitro vivo tiliacorinine may effective agent cca treatment stn","probabilities":0.9467213,"Title":"In Vitro And In Vivo Antitumor Activity Of Tiliacorinine In Human Cholangiocarcinoma","Abstract":"Cholangiocarcinoma (CCA) is a fatal cancer with poor prognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in unfavorable outcomes. At present, plant-derived compounds are gaining interest as potential cancer therapeutics, particularly for treatment-refractory cancers. In this study, antitumor activity of tiliacorinine, the major alkaloid isolated from a tropical plant, on CCA was first demonstrated. Antiproliferative effects of tiliacorinine on human CCA cell lines were investigated using SRB assays. Acridine orange/ethidium bromide staining, flow cytometric analysis and DNA laddering assays were used for apoptotic determination. Apoptosis-related proteins were verified by Western blotting and antitumor activity of tiliacorinine in vivo was demonstrated in CCA xenografted mice. Tiliacorinine significantly inhibited proliferation of human CCA cell lines with IC50 4.5-7 μM by inducing apoptosis through caspase activation, up- regulation of BAX, and down-regulation of BclxL and XIAP. Tiliacorinine considerably reduced tumor growth in CCA xenografted mice. These results demonstrated antitumor effects of tiliacorinine on human CCA in vitro and in vivo. Tiliacorinine may be an effective agent for CCA treatment.","Source":"STN","category":"ANIMAL","training_data":"In Vitro And In Vivo Antitumor Activity Of Tiliacorinine In Human Cholangiocarcinoma Cholangiocarcinoma (CCA) is a fatal cancer with poor prognosis and less than 10% of CCA patients can be offered surgical cure. Conventional chemotherapy results in unfavorable outcomes. At present, plant-derived compounds are gaining interest as potential cancer therapeutics, particularly for treatment-refractory cancers. In this study, antitumor activity of tiliacorinine, the major alkaloid isolated from a tropical plant, on CCA was first demonstrated. Antiproliferative effects of tiliacorinine on human CCA cell lines were investigated using SRB assays. Acridine orange/ethidium bromide staining, flow cytometric analysis and DNA laddering assays were used for apoptotic determination. Apoptosis-related proteins were verified by Western blotting and antitumor activity of tiliacorinine in vivo was demonstrated in CCA xenografted mice. Tiliacorinine significantly inhibited proliferation of human CCA cell lines with IC50 4.5-7 μM by inducing apoptosis through caspase activation, up- regulation of BAX, and down-regulation of BclxL and XIAP. Tiliacorinine considerably reduced tumor growth in CCA xenografted mice. These results demonstrated antitumor effects of tiliacorinine on human CCA in vitro and in vivo. Tiliacorinine may be an effective agent for CCA treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"effectiveness surgery recurrent cholangiocarcinoma single center experience brief literature review background study reviewed experiences previous studies surgery recurrent cholangiocarcinoma cca methods analyzed outcomes 117 patients recurrent cca 2000 2015 twenty one patients 17 9 underwent surgical resection recurrence remaining 96 patients 82 1 undergo resection evaluated patients clinicopathological features prognoses two groups results patients underwent surgery significantly associated better overall survival recurrence hr 0 22 p 0 0001 patients recurrent cca surgery recurrence independent better prognostic factor recurrence hr 0 27 p 0 0002 patients underwent surgery recurrent cca presence lymph node metastasis primary cancer independent worse prognostic factor hr 9 45 p 0 04 conclusions surgery recurrent cca may provide good survival impact selected patients patients lymph node metastasis primary cca undergo surgery recurrent cca pubmed","probabilities":0.9799733,"Title":"Effectiveness of surgery for recurrent cholangiocarcinoma: A single center experience and brief literature review","Abstract":"BACKGROUND: In this study, we reviewed our experiences and previous studies on surgery for recurrent cholangiocarcinoma (CCA). METHODS: We analyzed outcomes of 117 patients with recurrent CCA between 2000 and 2015. Twenty-one patients (17.9%) underwent surgical resection for recurrence, and the remaining 96 patients (82.1%) did not undergo resection. We evaluated patients' clinicopathological features and prognoses between the two groups. RESULTS: Patients who underwent surgery were significantly associated with better overall survival after recurrence (HR = 0.22, P < 0.0001). In patients with recurrent CCA, surgery for recurrence was an independent better prognostic factor after recurrence (HR = 0.27, P = 0.0002), and in patients who underwent surgery for recurrent CCA, the presence of lymph node metastasis of primary cancer was an independent worse prognostic factor (HR = 9.45, P = 0.04). CONCLUSIONS: Surgery for recurrent CCA may provide good survival impact in selected patients. Patients with lymph node metastasis of primary CCA should not undergo surgery for recurrent CCA.","Source":"PubMed","category":"HUMAN","training_data":"Effectiveness of surgery for recurrent cholangiocarcinoma: A single center experience and brief literature review BACKGROUND: In this study, we reviewed our experiences and previous studies on surgery for recurrent cholangiocarcinoma (CCA). METHODS: We analyzed outcomes of 117 patients with recurrent CCA between 2000 and 2015. Twenty-one patients (17.9%) underwent surgical resection for recurrence, and the remaining 96 patients (82.1%) did not undergo resection. We evaluated patients' clinicopathological features and prognoses between the two groups. RESULTS: Patients who underwent surgery were significantly associated with better overall survival after recurrence (HR = 0.22, P < 0.0001). In patients with recurrent CCA, surgery for recurrence was an independent better prognostic factor after recurrence (HR = 0.27, P = 0.0002), and in patients who underwent surgery for recurrent CCA, the presence of lymph node metastasis of primary cancer was an independent worse prognostic factor (HR = 9.45, P = 0.04). CONCLUSIONS: Surgery for recurrent CCA may provide good survival impact in selected patients. Patients with lymph node metastasis of primary CCA should not undergo surgery for recurrent CCA. PubMed","prediction_labels":"HUMAN"},{"cleaned":"guggulsterone induced apoptosis cholangiocarcinoma cells ros jnk signaling pathway cholangiocarcinoma cca common biliary tract malignancy arising bile duct epithelium global significantly increased morbidity mortality showed effect guggulsterone steroid found resin guggul plant human hucc t1 rbe cca cells exposure various concentrations guggulsterone multiple action time resulted significant apoptosis cca cells via activating extrinsic intrinsic pathways furthermore demonstrated apoptosis cca cells induced reactive oxygen species ros mediated jnk signaling pathway consistently inhibition jnk activity overexpression jbd binding protein reduction ros overexpression catalase decreased apoptotic cells results also revealed guggulsterone induced apoptosis coupled endoplasmic reticulum stress ers chop dependent pathway downregulation chop instead ers markers inhibit cca cell apoptosis taken together results showed guggulsterone induce apoptosis human cca cells ros jnk signaling pathway indicating guggulsterone important clinical therapy cca stn","probabilities":0.9467213,"Title":"Guggulsterone-Induced Apoptosis In Cholangiocarcinoma Cells Through Ros/Jnk Signaling Pathway","Abstract":"Cholangiocarcinoma (CCA), the most common biliary tract malignancy, is arising from the bile duct epithelium with the global significantly increased morbidity and mortality. Here, we showed the effect of guggulsterone, a steroid found in the resin of the guggul plant, on human HuCC-T1 and RBE CCA cells. Exposure to various concentrations of guggulsterone for multiple action time resulted in significant apoptosis in the CCA cells via activating both extrinsic and intrinsic pathways. Furthermore, we demonstrated that the apoptosis of CCA cells was induced by Reactive oxygen species (ROS) mediated JNK signaling pathway. Consistently, inhibition of JNK activity, overexpression of JBD, its binding protein or reduction of ROS by overexpression of catalase, all decreased apoptotic cells. Our results also revealed that guggulsterone-induced apoptosis was coupled with endoplasmic reticulum stress (ERS) in CHOP-dependent pathway. Downregulation of CHOP instead of other ERS markers could inhibit CCA cell apoptosis. Taken together, our results showed that guggulsterone could induce apoptosis of human CCA cells through ROS/JNK signaling pathway, indicating that guggulsterone could be important for the clinical therapy of CCA.","Source":"STN","category":"ANIMAL","training_data":"Guggulsterone-Induced Apoptosis In Cholangiocarcinoma Cells Through Ros/Jnk Signaling Pathway Cholangiocarcinoma (CCA), the most common biliary tract malignancy, is arising from the bile duct epithelium with the global significantly increased morbidity and mortality. Here, we showed the effect of guggulsterone, a steroid found in the resin of the guggul plant, on human HuCC-T1 and RBE CCA cells. Exposure to various concentrations of guggulsterone for multiple action time resulted in significant apoptosis in the CCA cells via activating both extrinsic and intrinsic pathways. Furthermore, we demonstrated that the apoptosis of CCA cells was induced by Reactive oxygen species (ROS) mediated JNK signaling pathway. Consistently, inhibition of JNK activity, overexpression of JBD, its binding protein or reduction of ROS by overexpression of catalase, all decreased apoptotic cells. Our results also revealed that guggulsterone-induced apoptosis was coupled with endoplasmic reticulum stress (ERS) in CHOP-dependent pathway. Downregulation of CHOP instead of other ERS markers could inhibit CCA cell apoptosis. Taken together, our results showed that guggulsterone could induce apoptosis of human CCA cells through ROS/JNK signaling pathway, indicating that guggulsterone could be important for the clinical therapy of CCA. STN","prediction_labels":"ANIMAL"},{"cleaned":"hepatoma derived growth factor novel prognostic biomarker intrahepatic cholangiocarcinoma hepatoma derived growth factor hdgf acidic heparin binding protein involved tumor progression poor prognosis kinds cancers aimed investigating functions hdgf intrahepatic cholangiocarcinoma ihcc detected expression hdgf immunohistochemistry 83 patients associations hdgf clinicopathologic features microvascular density mvd overall survival rates analyzed chi square method univariate multivariate analysis hdgf functions ihcc proliferation invasion angiogenesis detected mtt transwell tube formation assays respectively result found hdgf positive expression rate ihcc 51 8 43 83 ihcc hdgf expression significantly correlated mvd p 0 031 lymphatic invasion p 0 030 distant metastasis p 0 002 tnm stage p 0 037 hdgf identified independent prognostic factor ihcc kaplan meier method p 0 003 cox regression model p 0 008 moreover intracellular extracellular hdgf proved promote proliferation invasion angiogenesis ihcc cell lines conclusion hdgf identified independent prognostic biomarker ihcc hdgf promote ihcc cells progression including proliferation invasion angiogenesis indicating hdgf become new promising potential drug target ihcc pubmed","probabilities":1.0,"Title":"Hepatoma-derived growth factor: a novel prognostic biomarker in intrahepatic cholangiocarcinoma","Abstract":"Hepatoma-derived growth factor (HDGF) is an acidic heparin-binding protein involved in tumor progression and poor prognosis of kinds of cancers. Aimed at investigating the functions of HDGF in intrahepatic cholangiocarcinoma (IHCC), we detected the expression of HDGF by immunohistochemistry in 83 patients. Associations of HDGF with clinicopathologic features, microvascular density (MVD), and overall survival rates were further analyzed by Chi-square method, univariate or multivariate analysis. HDGF functions in IHCC proliferation, invasion, and angiogenesis were detected by MTT, transwell, and tube formation assays, respectively. As a result, we found that HDGF-positive expression rate in IHCC was 51.8 % (43/83) in IHCC. HDGF expression was significantly correlated to MVD (P = 0.031), lymphatic invasion (P = 0.030), distant metastasis (P = 0.002), and TNM stage (P = 0.037). HDGF was further identified as an independent prognostic factor in IHCC with Kaplan-Meier method (P = 0.003) and Cox-regression model (P = 0.008). Moreover, both intracellular and extracellular HDGF were proved to promote the proliferation, invasion, and angiogenesis of IHCC cell lines. In conclusion, HDGF was identified as an independent prognostic biomarker in IHCC. HDGF can promote IHCC cells progression, including proliferation, invasion, and angiogenesis, indicating HDGF could become a new promising and potential drug target of IHCC.","Source":"PubMed","category":"HUMAN","training_data":"Hepatoma-derived growth factor: a novel prognostic biomarker in intrahepatic cholangiocarcinoma Hepatoma-derived growth factor (HDGF) is an acidic heparin-binding protein involved in tumor progression and poor prognosis of kinds of cancers. Aimed at investigating the functions of HDGF in intrahepatic cholangiocarcinoma (IHCC), we detected the expression of HDGF by immunohistochemistry in 83 patients. Associations of HDGF with clinicopathologic features, microvascular density (MVD), and overall survival rates were further analyzed by Chi-square method, univariate or multivariate analysis. HDGF functions in IHCC proliferation, invasion, and angiogenesis were detected by MTT, transwell, and tube formation assays, respectively. As a result, we found that HDGF-positive expression rate in IHCC was 51.8 % (43/83) in IHCC. HDGF expression was significantly correlated to MVD (P = 0.031), lymphatic invasion (P = 0.030), distant metastasis (P = 0.002), and TNM stage (P = 0.037). HDGF was further identified as an independent prognostic factor in IHCC with Kaplan-Meier method (P = 0.003) and Cox-regression model (P = 0.008). Moreover, both intracellular and extracellular HDGF were proved to promote the proliferation, invasion, and angiogenesis of IHCC cell lines. In conclusion, HDGF was identified as an independent prognostic biomarker in IHCC. HDGF can promote IHCC cells progression, including proliferation, invasion, and angiogenesis, indicating HDGF could become a new promising and potential drug target of IHCC. PubMed","prediction_labels":"HUMAN"},{"cleaned":"mdm2 snp309 ethnicity dependent risk factor digestive tract cancers published data relationship t309g polymorphism murine double minute 2 mdm2 gene susceptibility digestive tract cancers dtc inconclusive thus aim study determine whether mdm2 t309g polymorphism associated risk diverse dtc including esophagus stomach liver bile duct pancreas colorectum cancers relevant studies identified october 1 2013 crude odds ratio 95 confidence interval ci used measure strength association pooled result based studies showed statistically significant link mdm2 t309g polymorphism dtc susceptibility vs g 0 82 95 ci 0 76 0 88 stratified race significant associations observed genetic models among asians especially chinese population among caucasians subgroup analyses according tumor location indicated genetic variant associated esophageal 0 88 95 ci 0 81 0 96 vs g hepatocellular 0 69 95 ci 0 57 0 84 vs g pancreatic cancer risk associated cholangiocarcinoma colorectum cancer susceptibility meanwhile g allele also suggested associated increased gastric cancer risk 0 68 95 ci 0 54 0 87 tt tg vs gg intestinal type gastric cancer 0 18 95 ci 0 06 0 50 tt vs gg helicobacter pylori infection positive stomach cancer study indicates mdm2 t309g polymorphism may ethnicity dependent risk factor dtc especially upper gastrointestinal tract malignancies pubmed","probabilities":0.9799733,"Title":"MDM2 SNP309 is an ethnicity-dependent risk factor for digestive tract cancers","Abstract":"Published data on the relationship between T309G polymorphism in the murine double minute 2 (MDM2) gene and susceptibility of digestive tract cancers (DTC) are inconclusive. Thus, the aim of this study is to determine whether MDM2 T309G polymorphism is associated with the risk of diverse DTC, including esophagus, stomach, liver, bile duct, pancreas, and colorectum cancers. Relevant studies were identified up to October 1, 2013. Crude odds ratio (OR) and 95% confidence interval (CI) were used as a measure of the strength of the association. The pooled result based on all studies showed that there was a statistically significant link between MDM2 T309G polymorphism and DTC susceptibility (T vs. G: OR = 0.82, 95%CI = 0.76-0.88). When stratified by race, significant associations were observed for all genetic models among Asians (especially in Chinese population), but not among Caucasians. Subgroup analyses according to tumor location indicated that the genetic variant was associated with esophageal (OR = 0.88, 95%CI = 0.81-0.96 for T vs. G), hepatocellular (OR = 0.69, 95%CI = 0.57-0.84 for T vs. G) and pancreatic cancer risk but not associated with cholangiocarcinoma or colorectum cancer susceptibility. Meanwhile, the G allele was also suggested to be associated with increased gastric cancer risk (OR = 0.68, 95%CI = 0.54-0.87 for TT + TG vs. GG for intestinal type of gastric cancer and OR = 0.18, 95%CI = 0.06-0.50 for TT vs. GG for Helicobacter pylori infection positive stomach cancer). Our study indicates that the MDM2 T309G polymorphism may be an ethnicity-dependent risk factor for DTC, especially for the upper gastrointestinal tract malignancies.","Source":"PubMed","category":"HUMAN","training_data":"MDM2 SNP309 is an ethnicity-dependent risk factor for digestive tract cancers Published data on the relationship between T309G polymorphism in the murine double minute 2 (MDM2) gene and susceptibility of digestive tract cancers (DTC) are inconclusive. Thus, the aim of this study is to determine whether MDM2 T309G polymorphism is associated with the risk of diverse DTC, including esophagus, stomach, liver, bile duct, pancreas, and colorectum cancers. Relevant studies were identified up to October 1, 2013. Crude odds ratio (OR) and 95% confidence interval (CI) were used as a measure of the strength of the association. The pooled result based on all studies showed that there was a statistically significant link between MDM2 T309G polymorphism and DTC susceptibility (T vs. G: OR = 0.82, 95%CI = 0.76-0.88). When stratified by race, significant associations were observed for all genetic models among Asians (especially in Chinese population), but not among Caucasians. Subgroup analyses according to tumor location indicated that the genetic variant was associated with esophageal (OR = 0.88, 95%CI = 0.81-0.96 for T vs. G), hepatocellular (OR = 0.69, 95%CI = 0.57-0.84 for T vs. G) and pancreatic cancer risk but not associated with cholangiocarcinoma or colorectum cancer susceptibility. Meanwhile, the G allele was also suggested to be associated with increased gastric cancer risk (OR = 0.68, 95%CI = 0.54-0.87 for TT + TG vs. GG for intestinal type of gastric cancer and OR = 0.18, 95%CI = 0.06-0.50 for TT vs. GG for Helicobacter pylori infection positive stomach cancer). Our study indicates that the MDM2 T309G polymorphism may be an ethnicity-dependent risk factor for DTC, especially for the upper gastrointestinal tract malignancies. PubMed","prediction_labels":"HUMAN"},{"cleaned":"interferon inducible protein 27 oncogene highly expressed cholangiocarcinoma patients poor survival objective cholangiocarcinoma cca devastating disease interferon inducible protein 27 ifi27 originally known involve innate immunity later found intervene cell proliferation leading inventive studies regarding role ifi27 cancer treatment aimed investigate role ifi27 cca materials methods cell proliferation migration invasion assays western blot gene transfection knockdown immunofluorescent immunohistochemical stains xenograft animal model applied results ifi27 knockdown cca cells induced cell cycle arrest phase resulting lower cell proliferative rate vitro vivo ifi27 knockdown attenuated cca cell migration invasion inhibition epithelial mesenchymal transition supported increased e cadherin decreased n cadherin fibronectin filamentous actin level also reduced ifi27 knockdown repressed expression secretion vascular endothelial growth factor vegf strong stimulator angiogenesis downregulation c jun c fos supported vitro finding human vascular endothelial cells grew slowly conditioned medium ifi27 knockdown cca cells vivo lower erythropoietin concentration found xenografted tumors derived ifi27 knockdown cca cells addition anti vegf antibody treatment able repress cca cell growth contrary ifi27 overexpression increase cca cell proliferation migration invasion clinically higher ifi27 expression linked inferior overall survival cca patients conclusion data strongly suggest ifi27 deemed potential target cca treatment stn","probabilities":0.9467213,"Title":"Interferon A-Inducible Protein 27 Is An Oncogene And Highly Expressed In Cholangiocarcinoma Patients With Poor Survival","Abstract":"Objective: Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to investigate the role of IFI27 in CCA. \r\n\r\n Materials and methods: Cell proliferation, migration, and invasion assays, Western blot, gene transfection and knockdown, immunofluorescent and immunohistochemical stains, and xenograft animal model were applied. \r\n\r\n Results: IFI27 knockdown in CCA cells induced cell cycle arrest in S phase, resulting in lower cell proliferative rate in vitro and in vivo. IFI27 knockdown attenuated CCA cell migration and invasion through inhibition of epithelial-mesenchymal transition, which was supported by increased E-cadherin and decreased N-cadherin and fibronectin. Filamentous actin level was also reduced. IFI27 knockdown further repressed expression and secretion of vascular endothelial growth factor (VEGF-A), a strong stimulator of angiogenesis, through downregulation of c-jun and c-fos, which was supported in vitro by the finding that human vascular endothelial cells grew more slowly in conditioned medium of IFI27 knockdown on CCA cells and in vivo by the lower erythropoietin concentration found in the xenografted tumors derived from IFI27 knockdown on CCA cells. In addition, anti-VEGF-A antibody treatment was able to repress CCA cell growth. To the contrary, IFI27 overexpression could increase CCA cell proliferation, migration, and invasion. Clinically, higher IFI27 expression was linked to inferior overall survival of CCA patients. \r\n\r\n Conclusion: Our data strongly suggest that IFI27 could be deemed as a potential target for CCA treatment.","Source":"STN","category":"ANIMAL","training_data":"Interferon A-Inducible Protein 27 Is An Oncogene And Highly Expressed In Cholangiocarcinoma Patients With Poor Survival Objective: Cholangiocarcinoma (CCA) is a devastating disease. Interferon α-inducible protein 27 (IFI27), originally known to involve in innate immunity, is later found to intervene in cell proliferation, leading to inventive studies regarding the role of IFI27 in cancer treatment. We aimed to investigate the role of IFI27 in CCA. \r\n\r\n Materials and methods: Cell proliferation, migration, and invasion assays, Western blot, gene transfection and knockdown, immunofluorescent and immunohistochemical stains, and xenograft animal model were applied. \r\n\r\n Results: IFI27 knockdown in CCA cells induced cell cycle arrest in S phase, resulting in lower cell proliferative rate in vitro and in vivo. IFI27 knockdown attenuated CCA cell migration and invasion through inhibition of epithelial-mesenchymal transition, which was supported by increased E-cadherin and decreased N-cadherin and fibronectin. Filamentous actin level was also reduced. IFI27 knockdown further repressed expression and secretion of vascular endothelial growth factor (VEGF-A), a strong stimulator of angiogenesis, through downregulation of c-jun and c-fos, which was supported in vitro by the finding that human vascular endothelial cells grew more slowly in conditioned medium of IFI27 knockdown on CCA cells and in vivo by the lower erythropoietin concentration found in the xenografted tumors derived from IFI27 knockdown on CCA cells. In addition, anti-VEGF-A antibody treatment was able to repress CCA cell growth. To the contrary, IFI27 overexpression could increase CCA cell proliferation, migration, and invasion. Clinically, higher IFI27 expression was linked to inferior overall survival of CCA patients. \r\n\r\n Conclusion: Our data strongly suggest that IFI27 could be deemed as a potential target for CCA treatment. STN","prediction_labels":"ANIMAL"},{"cleaned":"stathmin 1 expression predicts prognosis benefits adjuvant chemotherapy patients gallbladder carcinoma background abnormal expression stathmin 1 stmn1 plays important role proliferation migration gallbladder carcinoma gbc purpose current study investigate prognostic significance stmn1 gbc patients surgery methods stmn1 expression evaluated immunohistochemistry ihc tissue microarrays 70 gbc patients single institution 2009 2013 correlation stmn1 expression clinicopathological profiles prognosis statistically inspected results high expression stmn1 tumoral tissue associated poor tumor differentiation p 0 001 lymph node metastasis p 0 028 advanced tnm stage p 0 011 short overall survival p 0 001 cox multivariate analysis identified stmn1 expression independent prognostic factor integrating stmn1 expression current tnm staging system generate better clinical predictive model gbc moreover postoperative adjuvant chemotherapy act showed significant benefit tnm iii iv stage patients low stmn1 expression conclusion stmn1 might independent adverse prognostic factor gbc patients surgery combined tnm staging system improve predictive accuracy overall survival low expression stmn1 stratified subgroup advanced gbc patients benefit act stn","probabilities":0.7966102,"Title":"Stathmin 1 Expression Predicts Prognosis And Benefits From Adjuvant Chemotherapy In Patients With Gallbladder Carcinoma","Abstract":"Background: Abnormal expression of Stathmin 1(STMN1) plays an important role in the proliferation and migration of gallbladder carcinoma (GBC). The purpose of current study is to investigate the prognostic significance of STMN1 in GBC patients after surgery. \r\n\r\n Methods: STMN1 expression was evaluated with immunohistochemistry (IHC) on tissue microarrays from 70 GBC patients from a single institution between 2009 and 2013. The correlation between STMN1 expression and clinicopathological profiles and the prognosis was statistically inspected. \r\n\r\n Results: High expression of STMN1 in tumoral tissue was associated with poor tumor differentiation (P<0.001), lymph node metastasis (P=0.028), advanced TNM stage (P=0.011) and short overall survival (P<0.001). Cox multivariate analysis identified the STMN1 expression as an independent prognostic factor. Integrating STMN1 expression with current TNM staging system generate a better clinical predictive model for GBC. Moreover, the postoperative adjuvant chemotherapy (ACT) showed significant benefit in TNM III- IV stage patients with low STMN1 expression. \r\n\r\n Conclusion: STMN1 might be an independent adverse prognostic factor in GBC patients after surgery, which could be combined with TNM staging system to improve the predictive accuracy for overall survival. Low expression of STMN1 stratified a subgroup of advanced GBC patients who could benefit from ACT.","Source":"STN","category":"HUMAN","training_data":"Stathmin 1 Expression Predicts Prognosis And Benefits From Adjuvant Chemotherapy In Patients With Gallbladder Carcinoma Background: Abnormal expression of Stathmin 1(STMN1) plays an important role in the proliferation and migration of gallbladder carcinoma (GBC). The purpose of current study is to investigate the prognostic significance of STMN1 in GBC patients after surgery. \r\n\r\n Methods: STMN1 expression was evaluated with immunohistochemistry (IHC) on tissue microarrays from 70 GBC patients from a single institution between 2009 and 2013. The correlation between STMN1 expression and clinicopathological profiles and the prognosis was statistically inspected. \r\n\r\n Results: High expression of STMN1 in tumoral tissue was associated with poor tumor differentiation (P<0.001), lymph node metastasis (P=0.028), advanced TNM stage (P=0.011) and short overall survival (P<0.001). Cox multivariate analysis identified the STMN1 expression as an independent prognostic factor. Integrating STMN1 expression with current TNM staging system generate a better clinical predictive model for GBC. Moreover, the postoperative adjuvant chemotherapy (ACT) showed significant benefit in TNM III- IV stage patients with low STMN1 expression. \r\n\r\n Conclusion: STMN1 might be an independent adverse prognostic factor in GBC patients after surgery, which could be combined with TNM staging system to improve the predictive accuracy for overall survival. Low expression of STMN1 stratified a subgroup of advanced GBC patients who could benefit from ACT. STN","prediction_labels":"HUMAN"},{"cleaned":"diabetes liver cancer risk stronger effect whites blacks diabetes liver biliary tract cancer overrepresented among african americans limited information available interrelationship two diseases among african americans tested relationship diabetes incidence liver cancer whether relationship varied blacks whites using southern community cohort study conducted cancer follow 2002 2015 cohort mostly low income black white participants aged 40 79 n 17 644 without diabetes n 64 870 cohort entry mean age diabetes duration diabetes 55 0 9 5 years respectively mean age without diabetes 51 6 years logistic regression used compute ors 95 cis risk incident liver biliary tract cancer 429 incident cases cancers univariate analyses diabetes associated increased risk liver biliary tract cancer 1 73 95 ci 1 36 2 21 upon controlling age sex race bmi current former smoking total alcohol consumption hepatitis infection diabetes remained significant risk factor liver biliary tract cancer 1 49 95 ci 1 18 1 89 however stratified race risk associated diabetes significantly greater among whites 2 67 95 ci 1 71 4 19 blacks 1 28 0 98 1 68 pinteraction 002 furthermore controlling diabetes greatly attenuated higher risk liver biliary tract cancer among blacks indeed cancer risk among without diabetes twice high among blacks whites 2 01 95 ci 1 50 2 69 racial disparity observed among diabetes 0 95 95 ci 0 62 1 45 findings raise possibility markedly different impacts diabetes hepatic carcinogenesis blacks whites google scholar","probabilities":0.9799733,"Title":"Diabetes And Liver Cancer Risk-A Stronger Effect In Whites Than Blacks?","Abstract":"Both diabetes and liver and biliary tract cancer are overrepresented among African Americans, but limited information is available on the interrelationship of these two diseases among African Americans. We tested the relationship of diabetes with the incidence of liver cancer and whether this relationship varied between blacks and whites. Using the Southern Community Cohort Study, we conducted a cancer follow-up (2002-2015) of a cohort of mostly low income black and white participants aged 40-79 with (n=17,644) and without diabetes (n=64,870) at cohort entry. Mean age and diabetes duration of those with diabetes was 55.0 and 9.5 years, respectively. Mean age of those without diabetes was 51.6 years. Logistic regression was used to compute ORs (95% CIs) for the risk of incident liver and biliary tract cancer. There were 429 incident cases of these cancers. In univariate analyses, diabetes was associated with an increased risk of liver and biliary tract cancer (OR=1.73, 95% CI=1.36-2.21). Upon further controlling for age, sex, race, BMI, current and former smoking, total alcohol consumption, and any hepatitis infection, diabetes remained a significant risk factor for liver and biliary tract cancer (OR=1.49, 95% CI= 1.18-1.89). However, when stratified by race, risk associated with diabetes was significantly greater among whites (OR = 2.67, 95% CI = 1.71-4.19) than blacks (OR= 1.28, 0.98-1.68) (pinteraction=.002). Furthermore, controlling for diabetes greatly attenuated the higher risk of liver and biliary tract cancer among blacks; indeed, while the cancer risk among those without diabetes was twice as high among blacks than whites (OR=2.01, 95% CI = 1.50-2.69), no racial disparity was observed among those with diabetes (OR = 0.95, 95% CI= 0.62-1.45). The findings raise the possibility of markedly different impacts of diabetes on hepatic carcinogenesis between blacks and whites.","Source":"Google Scholar","category":"HUMAN","training_data":"Diabetes And Liver Cancer Risk-A Stronger Effect In Whites Than Blacks? Both diabetes and liver and biliary tract cancer are overrepresented among African Americans, but limited information is available on the interrelationship of these two diseases among African Americans. We tested the relationship of diabetes with the incidence of liver cancer and whether this relationship varied between blacks and whites. Using the Southern Community Cohort Study, we conducted a cancer follow-up (2002-2015) of a cohort of mostly low income black and white participants aged 40-79 with (n=17,644) and without diabetes (n=64,870) at cohort entry. Mean age and diabetes duration of those with diabetes was 55.0 and 9.5 years, respectively. Mean age of those without diabetes was 51.6 years. Logistic regression was used to compute ORs (95% CIs) for the risk of incident liver and biliary tract cancer. There were 429 incident cases of these cancers. In univariate analyses, diabetes was associated with an increased risk of liver and biliary tract cancer (OR=1.73, 95% CI=1.36-2.21). Upon further controlling for age, sex, race, BMI, current and former smoking, total alcohol consumption, and any hepatitis infection, diabetes remained a significant risk factor for liver and biliary tract cancer (OR=1.49, 95% CI= 1.18-1.89). However, when stratified by race, risk associated with diabetes was significantly greater among whites (OR = 2.67, 95% CI = 1.71-4.19) than blacks (OR= 1.28, 0.98-1.68) (pinteraction=.002). Furthermore, controlling for diabetes greatly attenuated the higher risk of liver and biliary tract cancer among blacks; indeed, while the cancer risk among those without diabetes was twice as high among blacks than whites (OR=2.01, 95% CI = 1.50-2.69), no racial disparity was observed among those with diabetes (OR = 0.95, 95% CI= 0.62-1.45). The findings raise the possibility of markedly different impacts of diabetes on hepatic carcinogenesis between blacks and whites. Google Scholar","prediction_labels":"HUMAN"},{"cleaned":"incidence survival gallbladder cancer three decades seer database study background gallbladder cancer gbc relatively rare malignancy dreary long term survival dearth literature incidence survival primary gbc recent decade especially respect socioeconomic status ses methods queried seer database primary gbc patients diagnosed three decades 1980 2009 using icd o 3 c23 9 9 original registry sites data obtained included demographics ses status treatment age adjusted incidence cause specific survival css relative survival rates rsr primary gbc results total 6 943 patients primary gbc reported 1980 2009 incidence gbc 100 000 decreased 1 3 1980s 1 0 1990s 0 8 2000s females showed higher incidence gbc 100 000 compared males three decades 1 6 vs 0 9 1980s 1 2 vs 0 6 1990s 1 0 vs 0 6 2000s stratified ses high poverty group showed highest incidence gbc 100 000 three decades 2 6 1 9 1 5 1980s 1990s 2000s respectively compared low medium poverty groups median css improved successive decade 4 5 months 1980s 6 2 months 1990s 8 3 months 2000s overall 5 year rsr increased 10 4 1980s 11 8 1990s 15 6 2000s p 0 0001 5 year rsr 2000s higher females 16 7 males 12 8 p 0 004 low poverty group consistently showed higher rsr compared high poverty group 6 months 12 months intervals three decades however difference wasn significant multivariate cox regression analysis gbc specific survival age rr 1 019 95 ci 1 017 1 021 p 0 001 sex female vs male rr 0 943 95 ci 0 917 0 969 p 0 001 found significant predictors survival conclusions analysis shows three decades overall rsrs median css improved successive decade incidence decreased 38 5 females higher incidence gbc throughout decades showed significantly increased survival rates males recent decade also incidence found higher high poverty group consistently google scholar","probabilities":0.9799733,"Title":"Incidence And Survival Of Gallbladder Cancer Over Three Decades: A Seer Database Study","Abstract":"Background: Gallbladder cancer (GBC) is relatively a rare malignancy with dreary long term survival. There is a dearth of literature on the incidence and survival of primary GBC in the most recent decade especially with respect to socioeconomic status (SES). Methods: We queried the SEER database for primary GBC patients diagnosed over three decades between 1980 and 2009 using ICD-O-3 C23.9 from the 9 original registry sites. Data obtained included the demographics, SES status, treatment, age adjusted incidence, cause specific survival (CSS) and relative survival rates (RSR) of primary GBC. Results: A total of 6,943 patients with primary GBC were reported between 1980-2009. The incidence of GBC/100,000 decreased from 1.3 in 1980s to 1.0 in 1990s to 0.8 in 2000s. Females showed a higher incidence of GBC/100,000 as compared to Males in all three decades (1.6 vs 0.9 in 1980s; 1.2 vs 0.6 in 1990s and 1.0 vs 0.6 in 2000s). When stratified by SES, the high poverty group showed highest incidence of GBC/100,000 in all the three decades (2.6, 1.9 and 1.5 in 1980s, 1990s and 2000s respectively) as compared to low and medium poverty groups. The median CSS improved with each successive decade from 4.5 months in 1980s to 6.2 months in 1990s to 8.3 months in 2000s. Overall 5- year RSR increased from 10.4% for 1980s to 11.8% for 1990s to 15.6% for 2000s (all p < 0.0001). The 5-year RSR in 2000s was higher in females (16.7%) than males (12.8%) (p = 0.004). The low-poverty group consistently showed higher RSR compared to high-poverty group at 6-months and 12-months intervals over three decades. However, this difference wasn’t significant. On multivariate cox regression analysis for GBC specific survival, age (RR: 1.019 95% CI 1.017-1.021; p < 0.001) and sex (Female vs Male: RR: 0.943 95% CI 0.917-0.969; p < 0.001) were found to be significant predictors of survival. Conclusions: Our analysis shows that, over the three decades, overall RSRs and median CSS have improved each successive decade, while the incidence has decreased by 38.5%. Females have higher incidence of GBC throughout all decades, but showed a significantly increased survival rates than males in the most recent decade. Also, the incidence was found to be higher in high poverty group consistently.","Source":"Google Scholar","category":"HUMAN","training_data":"Incidence And Survival Of Gallbladder Cancer Over Three Decades: A Seer Database Study Background: Gallbladder cancer (GBC) is relatively a rare malignancy with dreary long term survival. There is a dearth of literature on the incidence and survival of primary GBC in the most recent decade especially with respect to socioeconomic status (SES). Methods: We queried the SEER database for primary GBC patients diagnosed over three decades between 1980 and 2009 using ICD-O-3 C23.9 from the 9 original registry sites. Data obtained included the demographics, SES status, treatment, age adjusted incidence, cause specific survival (CSS) and relative survival rates (RSR) of primary GBC. Results: A total of 6,943 patients with primary GBC were reported between 1980-2009. The incidence of GBC/100,000 decreased from 1.3 in 1980s to 1.0 in 1990s to 0.8 in 2000s. Females showed a higher incidence of GBC/100,000 as compared to Males in all three decades (1.6 vs 0.9 in 1980s; 1.2 vs 0.6 in 1990s and 1.0 vs 0.6 in 2000s). When stratified by SES, the high poverty group showed highest incidence of GBC/100,000 in all the three decades (2.6, 1.9 and 1.5 in 1980s, 1990s and 2000s respectively) as compared to low and medium poverty groups. The median CSS improved with each successive decade from 4.5 months in 1980s to 6.2 months in 1990s to 8.3 months in 2000s. Overall 5- year RSR increased from 10.4% for 1980s to 11.8% for 1990s to 15.6% for 2000s (all p < 0.0001). The 5-year RSR in 2000s was higher in females (16.7%) than males (12.8%) (p = 0.004). The low-poverty group consistently showed higher RSR compared to high-poverty group at 6-months and 12-months intervals over three decades. However, this difference wasn’t significant. On multivariate cox regression analysis for GBC specific survival, age (RR: 1.019 95% CI 1.017-1.021; p < 0.001) and sex (Female vs Male: RR: 0.943 95% CI 0.917-0.969; p < 0.001) were found to be significant predictors of survival. Conclusions: Our analysis shows that, over the three decades, overall RSRs and median CSS have improved each successive decade, while the incidence has decreased by 38.5%. Females have higher incidence of GBC throughout all decades, but showed a significantly increased survival rates than males in the most recent decade. Also, the incidence was found to be higher in high poverty group consistently. Google Scholar","prediction_labels":"HUMAN"}]}}

------------------------------Captured stdout call------------------------------
{"Data":[{"RequestID":100739,"Filename":"train_data8_reference - Copy.xlsx","Status":"Save","Date":"2021-04-09 18:57:48"},{"RequestID":100740,"Filename":"train_data8_reference - Copy.xlsx","Status":"Save","Date":"2021-04-09 19:11:41"},{"RequestID":100807,"Filename":"train_data8_reference - Copy.xlsx","Status":"Save","Date":"2021-04-14 12:17:27"},{"RequestID":"fa320b305def5d8e77237b0b15c786bb","Filename":"train_data8_reference - Copy.xlsx","Status":"Save","Date":"2021-04-15 17:20:32"},{"RequestID":"d45056e009cef11e9edcef7f60ee64ad","Filename":"train_data8_reference - Copy.xlsx","Status":"100%","Date":"2021-04-16 09:22:37"},{"RequestID":"e5d45cc5cf3ee755f9d628dbbcc91497","Filename":"train_data8_reference - Copy.xlsx","Status":"15%","Date":"2021-04-16 12:54:52"},{"RequestID":"ef8f16205f40cc2707d1ea0e6474b5aa","Filename":"train_data8_reference - Copy.xlsx","Status":"15%","Date":"2021-04-16 12:59:10"},{"RequestID":"7ba4feb62f862f0a1d580c72a04fcc5e","Filename":"train_data8_reference - Copy.xlsx","Status":"15%","Date":"2021-04-16 12:59:12"}]}

------------------------------Captured stdout call------------------------------
{"Data":{"RequestID":"386f52d3d9fecdd99cbbe1eadba307fa","Username":"test@evalueserve.com","Status":"Save","Data":[{"Application Number":"CN104714006","Title":"一种检测奶制品中β-内酰胺酶的方法","Abstract":"本发明涉及一种检测奶制品中β-内酰胺酶的方法。所述方法设计了一个能被β-内酰胺酶特异性催化的荧光底物探针，该荧光底物探针的主要结构是由荧光素的母环和β-内酰胺类抗生素通过化学合成得到。β-内酰胺酶可以催化荧光底物探针发出强烈的荧光，根据反应得到的荧光强度计算β-内酰胺酶的含量。通过本发明的方法能检测到0.1ng/mL的β-内酰胺酶，比传统的ELISA方法灵敏度提高了两个数量级，检测时间缩短到45min，具有特异性强、灵敏度高、简便、检测快速等优点，而且可以大大降低检测费用。","Claims":"1.一种检测奶制品中β-内酰胺酶的方法，其特征在于，所述方法以荧光素-β-内酰胺类抗生素作为荧光底物探针进行酶促反应，根据反应得到的荧光强度计算β-内酰胺酶的含量。\n2.根据权利要求1所述的方法，其特征在于，所述荧光底物探针的浓度为0.1-1μM，优选为0.4μM；优选地，所述荧光底物探针对β-内酰胺酶具有广谱性。\n3.根据权利要求1或2所述的方法，其特征在于，所述荧光底物探针由荧光素和β-内酰胺类抗生素通过有机合成的方式合成；优选地，所述β-内酰胺类抗生素为青霉素、头孢菌素、头霉素或硫霉素中的任意一种，优选为青霉素或头孢菌素。\n4.根据权利要求1-3任一项所述的方法，其特征在于，所述酶促反应时间为5-60min，优选为10-30min，进一步优选为15min。\n5.根据权利要求1-4任一项所述的方法，其特征在于，所述方法包括在酶促反应前，进行β-内酰胺酶的富集；优选地，所述富集为利用免疫磁珠进行富集。\n6.根据权利要求1-5任一项所述的方法，其特征在于，所述方法包括以下步骤：(1)将免疫磁珠表面偶联上β-内酰胺酶抗体，得到特异性识别β-内酰胺酶的免疫磁珠探针；(2)将步骤(1)得到的免疫磁珠探针置于待测分析液中，形成抗原-抗体免疫磁珠复合物；(3)将步骤(2)得到的复合物进行磁分离，从而实现β-内酰胺酶的富集，得到免疫磁珠-β-内酰胺酶复合物；(4)向步骤(3)得到的免疫磁珠-β-内酰胺酶复合物中加入荧光底物探针进行酶促反应，根据反应得到的荧光强度计算β-内酰胺酶的含量。\n7.根据权利要求6所述的方法，其特征在于，步骤(1)所述免疫磁珠为超顺纳米磁珠；优选为粒径在200-2000nm的超顺纳米磁珠；优选地，所述免疫磁珠为具有60-100emu/g的比饱和磁化强度的免疫磁珠；优选地，所述偶联为共价偶联。\n8.根据权利要求6或7所述的方法，其特征在于，所述方法包括以下步骤：(1)采用比饱和磁化强度为60-100emu/g，粒径在200-2000的超顺纳米磁珠，通过共价偶联的方式将识别β-内酰胺酶的抗体偶联在超顺纳米磁珠的表面，制备成超顺纳米免疫磁珠，得到特异性识别β-内酰胺酶的免疫磁珠探针；(2)将步骤(1)得到的免疫磁珠探针置于待测分析液中，形成抗原-抗体免疫磁珠复合物；(3)将步骤(2)得到的复合物在室温下涡流震荡反应20min，然后进行磁分离，从而实现β-内酰胺酶的富集，得到免疫磁珠-β-内酰胺酶复合物；(4)向步骤(3)得到的免疫磁珠-β-内酰胺酶复合物中加入0.1-1μM的荧光素-β-内酰胺类抗生素作为荧光底物探针进行酶促反应5-60min，根据反应得到的荧光强度计算β-内酰胺酶的含量。","Description":"技术领域\n本发明涉及免疫检测技术领域，具体涉及一种检测奶制品中β-内酰胺酶的方法，尤其涉及一种基于荧光底物探针的荧光值定量检测奶制品中β-内酰胺酶的方法\n背景技术\n目前，青霉素和头孢菌素作为β-内酰胺类药物是治疗牛乳腺炎的首选，是牛奶中最常见的残留抗生素，而乳品中残留的抗生素危害食品安全和人体健康。我国无公害生鲜牛乳的产品标准中明文规定，生鲜牛乳中氨苄青霉素≤10μg/kg，青霉素不得检出。因此，国内多数乳品企业对抗生素残留超标的牛乳采取降价收购原则，出于经济利益的驱动，一些不法奶站为了谋求自己的经济利益，人为地使用一些生物制剂达到降解牛乳中残留的抗生素的目的，生产人造“无抗奶”。有研究表明，牛奶中的抗生素分解剂是革兰氏阳性菌产生的β-内酰胺酶，是人为添加的，而不是内源性β-内酰胺酶。β-内酰胺酶可以分解牛乳中的抗生素残留使其降到允许量。但是目前为止，尚未有关于β-内酰胺酶本身及其分解产物对人体是否健康的安全性评价标准，所以，国际食品法典委员会、欧盟、美国都不允许β-内酰胺酶在食品中使用，我国《食品添加剂使用卫生标准》(GB-2760)的食品用酶制剂名单中也不包括β-内酰胺酶。因此，β-内酰胺酶是非法的食品添加剂，目前国际和国内均不允许该酶在牛奶中作为添加剂使用。\n因此，确立针对这种人造“无抗奶”的违规情况，相应的检测方法具有十分重要的意义。目前比较成熟的检测方法主要包括高效液相色谱法、碘量法、微生物法、头孢菌素显色法、酸量法和免疫学方法。\n(1)微生物法可以定性和定量地检测牛奶中的β-内酰胺酶。该方法可以检测出牛奶中未反应完全(未失活)的β-内酰胺酶，可用于检测未经过任何加工的牛奶，检出限较低。但也存在检测种类有限、实验周期长、只能给出定性结论等局限性。不适用于快速、大规模的样品检测，但是，微生物法仍然是实验室检测牛奶中β-内酰胺酶的主要方法。\n(2)碘量法作为快速筛选方法，该法方便快捷、操作简单、试剂易得，检测革兰阳性细菌胞外酶阳性率高，为实验室所普遍使用。该方法可检出牛奶中已反应及未反应的β-内酰胺酶，可用于检测鲜奶及奶制品中的β-内酰胺酶，检出限较高。但该方法对反应时间等条件要求较严格，有假阳性和假阴性现象，每次试验均需要设置阳性和阴性对照，而且灵敏度较差，重现性差。碘量法虽然经典、快速，但其试剂配制较复杂，淀粉试剂易失效，必须现配现用。\n(3)酸量法简单易行，重复性好，最易获取结果，且较灵敏，结果稳定性好，假阳性和假阴性结果较少，适用于大多数实验室，虽然快速检测，但检测灵敏度偏低，且不能用于酶动力学分析。\n(4)高效液相色谱法具有检测时间短、可以定量分析等优点，但是存在灵敏度低、检测成本高、前处理操作复杂等缺点。\n(5)头孢菌素显色法：该方法比较方便快捷，操作简单，但是所用试剂价格昂贵，定量检测不准确。\n(6)免疫分析法可通过特异性抗体的制备，直接识别目标分子本身，特异性强，灵敏度高，成本低，不需要大型复杂的设备即可进行，但是传统的酶联免疫方法需要多步洗涤，比较耗时耗力，因此其使用也受到一定的限制。\nCN101710122A公开了一种快速免疫检测牛奶中β-内酰胺酶的方法，该方法利用包被与酶标板上的鼠抗β-内酰胺酶单克隆抗体，与兔抗β-内酰胺酶多克隆抗体和辣根过氧化物酶标记羊抗兔抗体组成三抗体夹心法试剂，进行三抗体夹心法免疫学检测。CN103134937A公开了一种检测牛奶中β-内酰胺酶的双抗体夹心法，该方法通过政策的免疫、细胞融合、筛选后得到15株β-内酰胺酶单克隆抗体，并与辣根过氧化物酶进行两两配对，以β-内酰胺酶为标准品建立了β-内酰胺酶的夹心ELISA分析方法。但这些方法都需要制备抗体，多次洗涤，耗时耗力。\n发明内容\n本发明的目的在于提供一种检测奶制品中β-内酰胺酶的方法，特别是一种基于荧光底物探针的荧光值定量检测奶制品中β-内酰胺酶的方法。该检测方法具有灵敏度高、特异性强、快速、简便等优点。\n为达此目的，本发明采用以下技术方案：\n本发明提供了一种检测奶制品中β-内酰胺酶的方法，该方法以荧光素-β-内酰胺类抗生素作为荧光底物探针进行酶促反应，根据反应得到的荧光强度计算β-内酰胺酶的含量。\n本发明中的荧光底物探针可以被β-内酰胺酶特异性地催化，其内酰胺键断裂，然后变成两个分子，其中一个为荧光素的基本结构单元，其荧光得到很大程度地增强，而该荧光强度和样品中的β-内酰胺酶的含量成正比，因此可以快速、特异性地检测β-内酰胺酶的含量。\n本发明中，所述荧光底物探针的浓度为0.1-1μM，例如可以是0.1μM、0.2μM、0.3μM、0.4μM、0.5μM、0.6μM、0.7μM、0.8μM、0.9μM或1μM，优选为0.4μM。\n优选地，所述荧光底物探针对β-内酰胺酶具有广谱性。\n本发明中，所述荧光底物探针由荧光素和β-内酰胺类抗生素通过有机合成的方式合成。本发明的荧光底物探针被β-内酰胺酶特异性催化的反应过程如下：\n本发明中，所述酶促反应时间为5-60min，例如可以是5min、10min、15min、20min、25min、30min、35min、40min、45min、50min、55min或60min，优选为10-30min，进一步优选为15min。\n本发明中，所述方法包括在酶促反应前，进行β-内酰胺酶的富集。\n优选地，所述富集为利用免疫磁珠进行富集。\n本发明通过采用免疫磁珠进行富集，可以从样品中特异性地捕获到β-内酰胺酶，然后洗涤，去掉非特异性吸附的杂质，提高了检测的灵敏度和准确性。\n作为优选技术方案，本发明所述的方法包括以下步骤：\n(1)将免疫磁珠表面偶联上β-内酰胺酶抗体，得到特异性识别β-内酰胺酶的免疫磁珠探针；\n(2)将步骤(1)得到的免疫磁珠探针置于待测分析液中，形成抗原-抗体免疫磁珠复合物；\n(3)将步骤(2)得到的复合物进行磁分离，从而实现β-内酰胺酶的富集，得到免疫磁珠-β-内酰胺酶复合物；\n(4)向步骤(3)得到的免疫磁珠-β-内酰胺酶复合物中加入荧光底物探针进行酶促反应，根据反应得到的荧光强度计算β-内酰胺酶的含量。\n本发明中，步骤(1)所述免疫磁珠为超顺纳米磁珠；优选为粒径在200-2000nm的超顺纳米磁珠，例如粒径可以是200nm、300nm、500nm、600nm、800nm、1000nm、1200nm、1500nm、1600nm、1800nm或2000nm。\n优选地，所述免疫磁珠为具有60-100emu/g的比饱和磁化强度的免疫磁珠，例如比饱和磁化强度可以是60emu/g、65emu/g、70emu/g、75emu/g、80emu/g、85emu/g、90emu/g、95emu/g或100emu/g。\n优选地，所述偶联为共价偶联。\n作为进一步优选的技术方案，本发明所述的方法具体包括以下步骤：\n(1)采用比饱和磁化强度为60-100emu/g，粒径在200-2000的超顺纳米磁珠，通过共价偶联的方式将识别β-内酰胺酶的抗体偶联在超顺纳米磁珠的表面，制备成超顺纳米免疫磁珠，得到特异性识别β-内酰胺酶的免疫磁珠探针；\n(2)将步骤(1)得到的免疫磁珠探针置于待测分析液中，形成抗原-抗体免疫磁珠复合物；\n(3)将步骤(2)得到的复合物在室温下涡流震荡反应20min，然后进行磁分离，从而实现β-内酰胺酶的富集，得到免疫磁珠-β-内酰胺酶复合物；\n(4)向步骤(3)得到的免疫磁珠-β-内酰胺酶复合物中加入0.1-1μM的荧光素-β-内酰胺类抗生素作为荧光底物探针进行酶促反应5-60min，根据反应得到的荧光强度计算β-内酰胺酶的含量。\n本发明中，所述荧光底物探针的激发波长为400-520nm，例如可以是400nm、410nm、420nm、430nm、440nm、450nm、460nm、470nm、480nm、490nm、500nm、510nm或520nm，优选为490nm。\n本发明中，所述荧光底物探针最大发射波长为450-550nm，例如可以是、450nm、460nm、470nm、480nm、490nm、500nm、510nm、515nm、520nm、525nm、530nm、535nm、540nm或550nm，优选为525nm。\n图1示出了本发明检测乳制品中β-内酰胺酶的原理，该检测原理具体如下：\n本发明利用荧光素-β-内酰胺类抗生素作为荧光底物探针进行酶促反应，该荧光探针底物可以被酶特异性地催化，其内酰胺键断裂，然后变成两个分子，其中一个为荧光素的基本结构单元，其荧光得到很大程度地增强，而且该荧光强度和样品中的β-内酰胺酶的含量成正比，从而实现了定量检测；另外，本发明通过酶促反应强的免疫磁珠富集，可以将β-内酰胺酶从复杂的牛奶样品中特异性地捕获并富集，有效去除了非特异性吸附的杂质，提高了检测的灵敏度和准确性。\n与现有技术相比，本发明至少具有如下有益效果：\n(1)本发明的方法能检测到0.1ng/mL的β-内酰胺酶，比传统的ELISA方法灵敏度提高了两个数量级，检测时间缩短到45min以内，具有特异性强、灵敏度高、简便、检测快速等优点；\n(2)本发明的方法可用于环境、临床样品和食品等液体样品中的β-内酰胺酶快速、灵敏地检测，而且可以大大降低检测费用，并且可以避免假阳性的出现，达到适合现场大规模样品筛查的目的，同时可以大大拓宽免疫磁珠的应用范围。\n附图说明\n图1是本发明检测奶制品中β-内酰胺酶的原理图。\n图2是本发明在不同酶促反应时间时的检测结果图。\n图3是本发明在不同荧光底物探针浓度时的检测结果图。\n图4是本发明在不同β-内酰胺酶浓度时的检测结果图。\n具体实施方式\n为更进一步阐述本发明所采取的技术手段及其效果，以下结合附图并通过具体实施方式来进一步说明本发明的技术方案，但本发明并非局限在实施例范围内。\n实施例中所用的试剂仪器设备来源：\n(1)超顺纳米磁珠(200nm-2000nm)由德国默克公司提供；\n(2)识别β-内酰胺酶的抗体购自abcam公司；\n(3)相关的有机试剂由国药化学试剂集团公司提供；\n(4)磁分离架：上海奥润微纳新材料科技有限公司。\n实施例1\n本实施例是利用荧光底物探针检测牛奶中的青霉素酶。\n将100μL 1μM的荧光底物探针加入到用一系列不同浓度的青霉素酶加标的牛奶中(牛奶样品的体积为1000μL，青霉素酶的浓度分别为1000ng/mL、100ng/mL、10ng/mL、1ng/mL、和0ng/mL)，在室温下震荡反应15min，然后测量每个样品的荧光值。通过荧光值和添加的青霉素酶的浓度之间的线性关系，可以得出牛奶中青霉素酶的含量。\n实施例2\n本实施例是利用荧光底物探针检测牛奶中的头孢菌素酶。\n将100μL 1μM荧光底物探针加入到用一系列不同浓度的头孢菌素酶加标的牛奶中(牛奶样品的体积为1000μL，头孢菌素酶的浓度分别为1000ng/mL、100ng/mL、10ng/mL、1ng/mL、和0ng/mL)，在室温下震荡反应15min，然后测量每个样品的荧光值。通过荧光值和添加的头孢菌素酶的浓度之间的线性关系，可以得出牛奶中头孢菌素酶的含量。\n实施例3\n本实施例是利用荧光底物探针检测牛奶中的头霉素酶。\n将100μL 1μM荧光底物探针加入到用一系列不同浓度的头霉素酶加标的牛奶中(牛奶样品的体积为1000μL，头孢菌素酶的浓度分别为1000ng/mL、100ng/mL、10ng/mL、1ng/mL、和0ng/mL)，在室温下震荡反应15min，然后测量每个样品的荧光值。通过荧光值和添加的头霉素酶的浓度之间的线性关系，可以得出牛奶中头霉素酶的含量。\n实施例4\n本实施例是利用免疫磁珠+荧光底物探针共同检测牛奶中的青霉素。\n1、免疫磁珠的制备\n将100μL 10mg/mL的纳米磁珠先悬浮于去离子水中，然后加入50μL浓度为10mg/mL的EDC溶液，在室温下活化反应半小时，然后磁分离，去掉上清液，加入2mL的PBS缓冲溶液(pH＝7.4，0.01M)悬浮。加入0.5mg抗体到上述的悬浮溶液中，在涡流震荡器上反应2h，然后加入500μL 3％的BSA溶液封闭，反应0.5小时，然后磁分离，去掉上清，加入1000μL的PBST溶液，重悬，在涡流震荡器反应3min，再磁分离，去掉上清液。该步骤重复2次，最后用包含有0.01％BSA的PBS溶液重悬，得到免疫磁珠，并在4℃冰箱保存。\n2、荧光底物探针的设计和筛选\n选用青霉素作为内酰胺键的母体结构，采用荧光素母体结构分子为荧光信号报告基团；将内酰胺类的抗生素分子和荧光素母体结构分子通过有机合成的方法合成荧光底物探针。\n3、对牛奶中青霉素酶的检测\n(1)将步骤(1)的免疫磁珠(100μL 0.2mg/mL)和2000μL的PBS混匀，在室温下涡流震荡反应20min，然后磁分离，用1000μL的磷酸吐温缓冲液涤液重悬，再进行磁分离，去掉杂质，最后用100μL的PBS缓冲溶液重悬；\n(2)向步骤(1)的混合溶液里面加入100μL浓度为0.4μM的荧光底物探针，在室温下涡流震荡分别反应5min、10min、15min和20min，最后磁分离，取上清液侧激发波长为490nm下和发射波长为525nm下的荧光强度。\n从图2可以看出，当反应时间为15min时，酶促反应基本达到平衡，因此反应15min可作为最佳的酶促反应时间。\n实施例5\n本实施例中免疫磁珠的制备以及荧光底物探针的设计和筛选如实施例4所示，对牛奶中青霉素酶的检测步骤如下：\n(1)将制得的免疫磁珠(100μL 0.2mg/mL)和5000μL的PBS混匀，在室温下涡流震荡反应20min，然后磁分离，用1000μL的PBST洗涤液重悬，再进行磁分离，去掉杂质，最后用100μL的PBS缓冲溶液重悬；\n(2)向步骤(1)的混合溶液里面分别加入100μL浓度为0.1μM、0.2μM、0.4μM和0.8μM的荧光底物探针，在室温下涡流震荡分别反应15min，最后磁分离，取上清液测激发波长在490nm下和发射波长在525nm下的荧光强度。\n从图3可以看出，荧光底物探针浓度为0.4μM时的效果最佳，因此采用0.4μM的浓度可作为最佳的荧光底物探针底物的浓度。\n实施例6\n本实施例中免疫磁珠的制备以及荧光底物探针的设计和筛选如实施例4所示，对牛奶中青霉素酶的检测步骤如下：\n(1)将制得的免疫磁珠(100μL 0.2mg/mL)和1000μL的PBS混匀，在室温下涡流震荡反应20min，然后磁分离，用1000μL的PBST洗涤液重悬，再进行磁分离，去掉杂质，最后用100μL的PBS缓冲溶液重悬；\n(2)向步骤(1)的混合溶液里面加入100μL浓度为0.2μM的荧光底物探针，在室温下涡流震荡反应15min，最后磁分离，取上清液测激发波长在490nm下和发射波长在525nm下的荧光强度；\n(3)基于荧光强度的变化和β-内酰胺酶浓度之间的关系，建立标准曲线；\n(4)将步骤(1)-(2)中的PBS缓冲液换成待测牛奶样品，再进行检测，根据标准曲线计算待测牛奶样品中的β-内酰胺酶的含量。\n从图4可以看出，该方法的最低检出限为0.1ng/mL，检测时间为45min。\n实施例7\n本实施例中免疫磁珠的制备以及荧光底物探针的设计和筛选如实施例4所示，对牛奶中头孢菌素酶的检测步骤如下：\n(1)将制得的免疫磁珠(100μL 0.1mg/mL)和1000μL的PBS混匀，在室温下涡流震荡反应20min，然后磁分离，用1000μL的PBST洗涤液重悬，再进行磁分离，去掉杂质，最后用100μL的PBS缓冲溶液重悬；\n(2)向步骤(1)的混合溶液里面加入100μL浓度为0.4μM的针对头孢菌素酶的荧光底物探针，在室温下涡流震荡反应15min，最后磁分离，取上清液测激发波长在490nm下和发射波长在525nm下的荧光强度；\n(3)绘制标准曲线：基于荧光强度的变化和β-内酰胺酶浓度之间的关系，绘制标准曲线；\n(4)将步骤(1)-(2)中的PBS缓冲液换成待测牛奶样品，再进行检测，根据标准曲线技术待测牛奶样品中的β-内酰胺酶的含量。\n通过检测，该方法的最低检出限为0.15ng/mL，检测时间为48min。\n综合实施例1-7，本发明方法能检测到最低为0.1ng/mL的β-内酰胺酶，比传统的ELISA方法灵敏度提高了两个数量级，检测时间缩短到45min，具有特异性强、灵敏度高、简便、检测快速等优点；同时本发明的方法为牛奶中β-内酰胺酶的检测提供一种有力的手段，为保证乳制品的安全，保障人民群众的身体健康发挥重要的作用。\n申请人声明，本发明通过上述实施例来说明本发明的详细方法，但本发明并不局限于上述详细方法，即不意味着本发明必须依赖上述详细方法才能实施。所属技术领域的技术人员应该明了，对本发明的任何改进，对本发明产品各原料的等效替换及辅助成分的添加、具体方式的选择等，均落在本发明的保护范围和公开范围之内。","Application Date":1434499200000,"IPC Class":"G01N33/53; G01N21/64","Applicant":"国家纳米科学中心","Relevance":"0"}]}}

------------------------------Captured stdout call------------------------------
{"TagData":{"filename":"test_api_english.xlsx","data":[{"Article":"No one has ever doubted the sheer consumerism of Indian festivity, but its presence reaches further than you would believe. For, all that data on what smartphones or shirts, boots or white goods that we buy and how we pay for it, rarely stays on our shores.This week’s festive season sales may generate online business of up to $3 billion. But much of the data from those sales, on ecommerce platforms and more, is likely to be hosted and stored in US data farms. While this has been happening since the start of online shopping and even earlier, this time, Reserve Bank of India (RBI) has firmly stated that all financial transactions’ data must be locally stored.This is driving data centre infrastructure spending, which could touch $4.5 billion by end of 2018 and $7 billion by 2020, according to real estate consultant Cushman & Wakefield’s blog on data centre growth in India. In fact, research and advisory firm Gartner sees data centre hardware spend alone to be $2.7 billion by 2018. India had built up data centre infrastructure of 1.3 million square feet in 2008, expected to scale to 10.9 million sq feet by end of 2018, says Cushman & Wakefield. By 2050, India will be at number 5 spot in size of data centre market.This explosion will be driven by localisation and backed by clichés — data is the new oil, why should data of over one billion Indians not be in India, data is strategic and foreign entities could cripple India in event of war or sanctions, how will Indian law enforcement go after data gangs in Macau, Moscow, Madrid or Manhattan if systems are compromised and so on.Kartik Shinde, partner, cybersecurity, EY India, says, “If the end beneficiary is in Macau, where there are a lot of casinos, you have to liaise with lawyers in Macau.That’s easier said than done. Fraudsters (in and outside India) study the system and number of hops (number of countries and banks it goes via), say for money transfer, and devise the best way to defraud.”The benefits are obvious. Rakshit Daga, vice-president, engineering, BigBasket, says, “It will speed up transactions and reduce network latency.” When the online grocery store shifted its data centre (hosted on Amazon Web Services) from Singapore to Mumbai, it noticed up to 10 per cent improvements in transaction efficiency. “Shifting from the US to India could lead to up to 30 per cent better speeds,” he adds.A chief information officer of a multinational manufacturing firm, which has been keeping Asia Pacific enterprise data in India for the past four years, says it saved 30-40 per cent in costs. India is an ideal location for lower cost of operations, availability of quality talent and round-the-clock service, he says.B Srinivasa Rao, chief marketing officer, CtrlS Datacentres, which runs Asia’s largest tier IV data centres in Hyderabad, Mumbai and Gurgaon, says many ecommerce and fintech clients see India as a cost saver. The manpower, real estate and bandwidth costs come down by about 80 per cent compared to a top-tier data centre in the US or Singapore. Imran Iraqi, principal, financial technology services, CtrlS, believes it will continue to grow at the same pace over the next five years.CtrlS is spending Rs 1,500 crore on setting up hyperscale data centres in Hyderabad and Mumbai, which would require about 100MW and 50MW, respectively. NetMagic, acquired by Japan’s NTT Com in 2012, has nine data hosting facilities in India, two of which were set up early this year at an investment of $144 million. Flipkart ’s PhonePe and Alibaba-backed Paytm claim their transactions are processed locally.Siddharth Vishwanath, partner, cybersecurity, PwC India, says, “Global companies will need to invest more in infrastructure development and re-architect the way applications work.” He points out that companies such as Google Pay, which have a common global data backbone for multiple countries, will also need a separate one for India to comply with local regulations.“Data is a digital transactions footprint. During war or hostilities, data centres could be switched off. Such scenarios, among others, are pushing countries towards local infrastructure,” he adds.Even when an Indian user shops at Macy’s in New York on an Indian bank’s credit card, transactions may be routed via Wells Fargo (which issues card swipe machines to Macy’s) in the US and stored there rather than in India (See graphic).Some companies are insisting on mirroring rather than storing information only in India. Earlier this month, WhatsApp said it has built a system to store payments-related data locally in India through mirroring. “We hope to expand WhatsApp payments to all of India soon so we can contribute to financial inclusion goals,” a company statement noted.But mirroring has not cut ice. “It’s like a photocopy. The original will be outside India. Mirroring is not good enough,” says Shinde of EY India. Vishwanath adds, “Mirroring is a subset. The regulator is stating that data cannot go out, so mirroring is not a solution.”The banking regulator insisted on hard localisation by October 15, though global payments companies have been lobbying with the finance ministry and RBI for relaxation. Some have sought a year’s extension but to no avail so far.Among reasons for local hosting are ease of access for law enforcement and privacy. However, Prashant Pradhan, vice-president, IBM Asia Pacific, says, “Physical location does not eliminate need for protocols and permissions to access. Situations (like sanctions or war) might be driving intent, but access is not controlled by the Government of India but by the owner.”Global tech and payments giants consider forced localisation against the grain of free trade and data flow. In a stronglyworded letter to Prime Minister Narendra Modi, US Senators John Cornyn and Mark Warner — co-chairs of the Senate’s India caucus that comprises over 30 members — urged India to instead adopt a “light touch” regulatory framework that would allow data to flow freely cross-border.“We see this as a fundamental issue to further development of digital trade and one that is crucial to our economic partnership,” they wrote on October 12.Echoing the sentiment, Mukesh Aghi, chief executive, US India Strategic Partnership Forum (USISPF), says the forum supports free flow of data and opposes forced data localisation . USISPF is a trade body representing US corporates in India, such as Visa, MasterCard. Amex, Amazon and Western Union, among others.“We expect these requirements (of local centres) to raise cost of procuring and delivering services, including for local Indian businesses, which will ultimately increase costs and reduce availability of data-dependent services.”","Category":"Investment"},{"Article":"Currently, there are around 16 new Fixed Maturity Plans (FMPs) open for subscription in the market. Many prominent fund houses such as Reliance Mutual Fund, Tata Mutual Fund, Axis Mutual Fund, HDFC Mutual Fund, among others, have lined up FMPs.\n\nNew Delhi: Air-conditioner and commercial refrigeration major Blue Star is looking to further consolidate its position in the room air-conditioning segment as it aims to be USD 1 billion plus company in the next five years, said a top company official. The home-grown Bluestar , which on Thursday turned 75 years old, is also bullish on its growth outlook in the overseas market. The company has plans to expand its size in the water purifier market.Bluestar would expand its network in the overseas markets, where it is operating, and is aiming to have a turnover of Rs 1,000 crore in the next three years.\"We have a goal that from five years from now, we as an 80-year old company should have a turnover of Rs 8,000 crore (USD 1.1 billion). That is our internal goal to be a billion dollar company by FY 2024,\" Bluestar Joint Managing Director B Thiagarajan told .He further said: \"The growth would come from all segments B2B and B2C from the domestic and international markets.\"In FY 2017-18, the Mumbai-based company had registered a revenue of Rs 4,433.34 crore.Bluestar is also in the process of fast indigenisation and backward integration.\"Massive focus in the next 2-3 years would be on the backward integration as the trade barriers would continue to bother us,\" Thiagarajan said.The company would also improve its electro mechanical business and special refrigeration projects in B2B segment as the market seems to be reviving, he said.Bluestar, which presently gets around Rs 600 crore from the international markets, has plans to increase the global contribution to around Rs 1,000 crore in the next three years.\"We would keep expanding our footprints in terms of distribution reach in terms. Today we do a turnover of Rs 600 crore and we may be doing around Rs 1,000 crore within three years,\" Thiagarajan added.Bluestar has presence around 19 countries, mainly in gulf, Middle East and African markets in B2B and B2C space.On being asked about the government's decision to hike the basic customs duty (BCD) on compressors and AC units (fully imported), he said that this would impact the festive season sales.\"This would be passed on to the consumers, prices would go up. Moreover, disposable income is down because the hike in fuel prices... Therefore, I am of the opinion that festival season demand would be impacted,\" Thiagarajan said.Established during World War II on September 27, 1943, by Mohan T Advani as a three-member team repairing and reconditioning air conditioners and refrigerators,Blue Star is a leading player in the AC and commercial refrigeration industry in India.","Category":"Negative news"},{"Article":"Value fashion and lifestyle products retailer V-Mart Retail , which primarily operates in smaller towns, is evaluating a omni-channel (offline and online retail) strategy to expand business and reach its customers.The company is also looking at investing Rs 100 crore next fiscal to open new stores and setting up a new warehouse.V-Mart primarily operates in tier II, tier III and tier IV cities and follows a cluster-based model approach to expand and has a set a target to invest Rs 300 crore to double store count and treble its turnover to Rs 3,500 crore in the next five years.\"We are considering an omni-channel strategy and plan to get into online retail to reach our customers. It may happen by end of next year,\" V-Mart Retail chairman and managing director Lalit Agarwal told PTI.It currently operates about 185 outlets in over a dozen states in India. The company plans to add more than 200 stores in the next five years to create a network of 400 outlets.In 2017-18, the company had reported a revenue of over Rs 1,200 crore.The company also plans to invest Rs 100 crore next fiscal to open new stores and set up a new warehouse in the country.\"We are looking at setting up a new warehouse to service our stores. It will come up in Uttar Pradesh or Bihar,\" Agarwal said.About 75 per cent of V-Mart's stores are located in just four states -- Uttar Pradesh, Uttarakhand Jharkhand and Bihar.V-Mart, at present, has a distribution centre located near Gurgaon to service all its stores.","Category":"Negative news"},{"Article":"Making it mandatory for e-commerce players operating in the country to store user data exclusively in India will impact their business, according to industry experts.An initial draft policy discussed at a meeting of a high-level think-tank set up to formulate a national e-commerce policy has suggested that all e-commerce companies will have to store user data exclusively in India in view of security and privacy concerns.Pratibha Jain, Partner, Nishit Desai Associates said that data localisation would not help in resolving privacy concerns.\"Whether I keep a copy in India or offshore as long as the service provider signs a confidentiality agreement which is enforceable expeditiously... the only thing that then matters to me is the economics.\"As long as companies agree to provide access to the government, location of storage should not be a concern. On the other hand, enforcing data localisation may increase the cost of business for start-ups,\" she said.Jain added that any policy should have three mantras -- job creation, promoting exports and consumer protection.Another expert from the industry, who did not wish to be named, shared similar views and said that several budding entrepreneurs are venturing into e-commerce field and to help them grow, the government should not make it mandatory to store user data in the country.However, some experts stated that the government should not allow firms to store data outside country as there are security related concerns.Professor Biswajit Dhar of Jawaharlal Nehru University said that data localisation is important for India and that cannot be shared with anyone.\"User data should be stored in India. The data movement is tracked by multinational firms and from that they are making commercial gains. The government has to take stand on this important issue and framing of the national e-commerce policy would help in taking a strong stand in the issue in the WTO,\" he added.Several members, particularly the developed countries in the World Trade Organisation (WTO), are demanding discussions on liberalising e-commerce trade and for that India needs to first formulate a domestic policy for the fast-growing sector.A high-level committee has been constituted recently by the government to take a look at all the issues concerning this sector, including definition, payment systems and logistics related matters.","Category":"Risk"},{"Article":"In February, PC Jeweller had acquired premium bridal gold jewellery brand AZVA from the World Gold Council (WGC) for an undisclosed amount.\n\nNEW DELHI: P C Jeweller will raise up to Rs 257 crore through issue of preferential shares to US-based investment firm Fidelity for business expansion In May, the national capital-based firm had raised Rs 427 crore from DVI Fund Mauritius by allotting it compulsorily convertible debentures.P C Jeweller today informed BSE that its board has approved the issue of compulsorily convertible preference shares for an aggregate amount of up to Rs 257.37 crore on private placement basis.When contacted, PC Jeweller Managing Director Balram Garg said: \"We will raise up to Rs 257 crore from Fidelity. The proceeds from DVI Fund and Fidelity would be utilised as capital expenditure for future expansion.\"We had a target to raise about Rs 600-700 crore and the same has been completed.\"Garg said the company is adding more stores every fiscal and is exploring to set up new manufacturing facilities . It has three factories and about 60 retail stores across the country.In February, PC Jeweller had acquired premium bridal gold jewellery brand AZVA from the World Gold Council (WGC) for an undisclosed amount.The company's stock closed at Rs 430.15, up 1.16 per cent, apiece on BSE.","Category":"Cooperation"},{"Article":"Earlier, PC Jeweller Managing Director Balram Garg had said that the funds would be utilised as capital expenditure for future expansion.\n\nNEW DELHI: PC Jeweller Ltd has raised Rs 427 crore from DVI Fund Mauritius by allotting it compulsorily convertible debentures and the amount is to be used for business expansion In a filing to the BSE today, PC Jeweller informed that \"the board of directors of the company in its meeting held today allotted 42,69,984 compulsorily convertible debentures having face value of Rs 1,000 to DVI Fund (Mauritius) Ltd for an aggregate amount of Rs 426,99,84,000.\"The conversion rate has been fixed at Rs 380.Last month, the board had approved the issue of compulsorily convertible debentures for an aggregate amount of up to Rs 427 crore by way of a preferential allotment on private placement basis to DVI Fund Mauritius.Earlier, PC Jeweller Managing Director Balram Garg had said that the funds would be utilised as capital expenditure for future expansion.The company currently has three factories and 60 retail stores across the country.PC Jeweller is adding 15-20 stores every fiscal and is exploring to set up new manufacturing facilities.","Category":"Cooperation"},{"Article":"FILE PHOTO: The company, which is already a 30,000-people strong organisation, is looking to invest about Rs 200 crore for its expansion plans.\n\nNEW DELHI: Jubilant FoodWorks , that holds the master franchise for Domino’s Pizza in India, Nepal, Sri Lanka and Bangladesh and also for Dunkin’ Donuts in India, plans to add around 5,000 employees by this fiscal ending March 2016. Most of these new recruits will be to man its 150 new Domino’s Pizza stores and 40 new Dunkin’ Donuts stores in India.The company, which is already a 30,000-people strong organisation, is looking to invest about Rs 200 crore for its expansion plans. Further, it is planning to set up a state-of-the-art factory in Greater Noida. “This will be the first of its kind in the world for Domino’s Pizza. This is going to be a total green facility,” Ajay Kaul , chief executive officer of Jubilant FoodWorks, told ET.“Unlike most other companies (competitors including food delivery startups), we are on an expansion phase,” he said. Lately, online food delivery start-ups such as TinyOwl , Zomato, Dazo and SpoonJoy have laid off employees as a result of high costs and low returns. Other online food delivery business companies are struggling too. Not too long ago, these food delivery startups were on a hiring spree, but with high costs and not enough returns they are now being forced to either shut down or cut costs.“Last two years have been tough for all in the food business as customers have hung on to their wallets. Yet, Jubilant did well,” Kaul said. In February, the company is about to open its 1000th Domino’s Pizza store. It currently has about 950 such stores.Pizza is still the revenue driver for Jubilant FoodWorks and India is the second largest market for its pizza business after the US. Jubilant FoodWorks operates Domino’s Pizza brand with the exclusive rights for India, Nepal, Bangladesh and Sri Lanka and in India it has around 70% market share.The company launched Dunkin’ Donuts in India in April 2012 in Delhi and has 67 Dunkin’ Donuts restaurants in India.","Category":"Negative news"},{"Article":"Accept the updated privacy & cookie policy\n\nDear user,\n\n\n\nThe EconomicTimes.com privacy and cookie policy has been updated to align with the new data regulations in European Union. Please review and accept these changes below to continue using the website.\n\n\n\nYou can see our privacy policy & our cookie list below. We use cookies to ensure the best experience for you on our website.\n\n\n\nIf you choose to ignore this message, we'll assume that you are happy to receive all cookies on ET Retail.","Category":"Investment"},{"Article":"FILE PHOTO: OYO Rooms is piloting a food technology venture and an on-demand housekeeping service as it looks to offer its customers a better experience.\n\nBENGALURU: Budget hotels aggregator Oyo Rooms is piloting a food technology venture and an on-demand housekeeping service as it looks to offer its customers a better experience while creating a sustainable and standardized long-term brand.With Oyo Cafe , the company will aggregate its listed hotels' kitchens to prepare food, which it will sell under its own brand.\"As in any food business, we noticed that our partner hotels' kitchen have excess inventory,\" said Maninder Gulati, head of strategy and corporate development at Oyo.\"So, the idea is, if we can utilise that and use food tech platforms like Zomato or Swiggy to distribute that food then that's a revenue generation potential for our partner.\"Gulati said Oyo Care, the on-demand housekeeping services venture, is a larger experiment. \"That is an on-demand cleaning service. Our area managers can facilitate cleanup for a room as and when a customer needs it,\" he said.Gulati, a former venture capital investor, joined Oyo in October. He was earlier a principal at Lightspeed Venture Partners India, a venture fund which is an investor in Oyo Rooms.Oyo has been roping in unbranded, small hotels with attractive minimum guarantee deals, which ensures them revenues. This inventory of hotel rooms is then being sold at discounted prices to get new customers hooked on to the branded budget stay, which have standard amenities.Gulati said over the last two years, the Gurgaon-based company has seen people from all walks of life check in to Oyo rooms. \"From angel investors who would want to cut down on travel time and, therefore, pick the nearest OYO, to students who gather on a Saturday night to watch a match together, we have seen all sorts of use cases for Oyo,\" he said.Since raising $100 million in August in a round led by SoftBank , Oyo has aggressively expanded its network to 30,000 rooms in over 3,000 properties across 130 Indian cities and towns from 12,000 rooms in 1,200 properties in 73 cities. Oyo had earlier said that it is targeting over 50,000 rooms in 5,000 properties by the end of 2015.Experts say since Oyo is discounting most of its properties to incentivise customers, adding new services becomes critical for its success in the long term. On the other hand, the company is burning cash to block inventory in its partner hotels.\"We want to contribute to 80% of business that these hotels get, therefore, we take the significant number of rooms in each property,\" Gulati said.Oyo competes with Tiger Global-backed Zo Rooms, Treebo Hotels, Fabhotels, Wudstay, Zen Rooms, Zip Rooms, Vista Rooms and RoomOnCall.Online travel aggregator Make-Mytrip has come up with its own brand of budget rooms with the launch of Value+. In September, Goibibo launched its own platform, GoStays, to facilitate booking budget accommodation.","Category":"Investment"},{"Article":"NEW DELHI: You may soon be able to gorge on burgers from Burger King in your office canteen . After having set up shops in airports and the Delhi Metro, the world's second largest quick-service burger chain is all set to widen its footprint into corporate offices across India.\"Technology has changed the way people access food across the world. The way e-commerce has changed the growth of food delivery business in India is not even funny. For instance, in the US market, quick-service restaurants (QSRs) are present in Walmarts, on ships, in trains and even in army bases. In India, we need to think of new ways of getting closer to the consumer,\" Rajeev Varman , CEO at Burger King India, told TOI.Varman, who spearheaded the Miami-based burger chain's turnaround in the UK, is betting on innovation to fast-forward its growth in India. Burger King was one of the first QSR chains to launch its products on eBay and Paytm . In one year of its operations here, the company has opened 28 outlets and is planning to open 12 more by the year-end at an investment of Rs 1.75-3 crore each.Varman, however, refused to divulge long-term numbers. \"I look at the business quarter by quarter. At store level, we have been profitable from day one. At company level, it will take us a few more stores and months to reach there,\" he said.The burger chain, known for its signature burger the Whopper, is currently toying with the idea of launching rice-based products here. \"We are piloting the products in Bangalore, where we are trying different combinations with rice such as crispy fried chicken, fiery chicken wings and gravy,\" said Varman.However, he said vegetarian options are the prime focus for the company here. \"India is the only market in the world where we sell three different Whoppers, including vegetarian ones. Across the year, the split in veg-non-veg sales is around 50:50. But here, even non-veg consumers turn veg on certain days of the week due to religious reasons. During festivals such as Navratri, the split between veg and non-veg sales at our stores goes up to 65:35,\" he said.On Burger King's rivalry with McDonald's, which entered the country in 1996, Varman said organized players only constitute 2% of India's QSR market, which is set to double in size to around $1.1 billion between 2013 and 2016, according to the Economist Intelligence Unit. \"The aim is to penetrate the 98%,\" he said.","Category":"Risk"},{"Article":"FILE PHOTO: “We have just entered the consumer retail market. Our products will now be available in modern retail stores across the country. We expect to grow at a tremendous pace,” said Viraj Bahl, founder and managing director of Veeba Foods. (Photo credit: Thinkstock Images/Getty Images)\n\nNew Delhi: Veeba Foods Services , the supplier of sauces, dressings and other ingredients to restaurants, will now offer its products directly to retail customers at outlets such as More and Future Group’s FoodHall “We have just entered the consumer retail market. Our products will now be available in modern retail stores across the country. We expect to grow at a tremendous pace,” said Viraj Bahl , founder and managing director of Veeba Foods.With this diversification, the company expects to reach a turnover target of Rs 400 crore by 2019. Monthly revenue has been about Rs 1 crore, he said.Veeba plans to expand its distribution network to 1,000 by the end of 2016 from 400 currently. The company will enter the northeast, which is the only part of the country where its products are not available.Founded in 2013, Veeba Foods emerged after the previous Bahl family enterprise Fun Foods was sold to German group Oetker. Since then, Veeba has raised $8 million (Rs 38 crore) from DSG Consumer Partners and Saama Capital. The last fund raising took place six months ago, according to Bahl.Veeba manufactures sauces and dressings and its customers include Domino’s Pizza, KFC, Pizza Hut, Burger King, Taco Bell and Starbucks.","Category":"Acquisition"},{"Article":"Ready-to-cook food startup Chefs Basket has raised $6 million (about Rs 40 crore) in Series A funding from SAIF partners and India Value Fund Advisor's partner Haresh Chawla, an angel investor in the startup who also participated in this round in his personal capacity.\n\nMUMBAI: Ready-to-cook food startup Chefs Basket has raised $6 million (about Rs 40 crore) in series A funding from SAIF partners and India Value Fund Advisor's partner Haresh Chawla, an angel investor in the startup who also participated in this round in his personal capacity.The company, founded in 2012 by three IIT Bombay batchmates, plans to use the funds to expand its range of products and add new distribution channels. It currently sells ready to cook packaged food under Chefs Basket brand.“This funding will help us take Chefs Basket to the next level of growth and we plan to expand the brand to the top 15 cities of India, with a portfolio of 30 SKUs (stock keeping units) by the end of March 2016,” said Varun Jhawar, co-founder of Fizzy Foodlabs, which owns Chefs Basket.Jhawar said the company has raised the money by issuing fresh equity to the investors and Vishal Sood, partner at SAIF partners will represent the fund on the board of the startup.Chefs Basket plans to expand its portfolio to introduce single serve format in oriental cuisine, a range of fresh products with lower shelf life and also launch its own range of pasta sauces.“Chefs Basket’s business is attractive because as India is growing and the consumption patterns are increasing, this category will become big. Right now, the ready to cook category is small in India and it is expected to grow 10-20x in the next couple of years,” said Mukul Singhal, partner, SAIF Partners.The company currently offers Italian, Mexican, Oriental and Thai dishes in two ready to cook formats at Rs 75-300.Chefs Basket sells about 1.3 lakh units of single serve packs a month and almost 90% of the sales come from hypermarkets, according to Jhawar, who said the company targets to ramp up sales to 4-5 lakh units a month by March 2016.The company has partnered e-commerce websites including Amazon, Flipkart Snapdeal , BigBasket, Paytm and Grofers , along with supermarket chains Hypercity, D-Mart and Big Bazaar to sell its products.“We entered a white space category where there are not many competitors,” said Nipun Katyal, one of the three founders of the company. \"World cuisine as a segment is booming in the Indian food service space and we wanted to bring these cuisines into the homes of the end users.”Chefs Basket has a panel of 12 chefs who are responsible for product development. “These chefs have been associated with famous restaurants like Little Italy, Spaghetti Kitchen, Sancho’s, Renaissance (Fratelli Fresh) and India Jones (Trident),” said Katyal.With growing portfolio, the startup also plans to strengthen its marketing, sales and operations team. Co-founder Manish Tirthani said the company is setting up a research and development unit cum pilot plant in Mumbai to get deeper into product categories.“We are also entering the international markets and this will happen through our channel partners who already have a connect in these markets,” said Tirthani.The company will introduce its range of Italian products in South Africa, Canada and Australia by January 2016, he said.According to industry estimates, the ready to cook industry in India is expected to grow 20-25% every year over the next five years.","Category":"Cooperation"},{"Article":"As part of the partnership, TIL is licensing its Colombia Traffic Network (CTN) technology to LocoVida to power their advertising campaigns for brands wanting to reach the tier-II and tier-III audience.\n\nNew Delhi: Mobile payments network MobiKwik has partnered with Archies Sagar Ratna and Mobilti World as part of it offline retail expansion strategy said the company in a press release.“It is the rapid adoption of smartphones and mobile e-commerce in India that is rendering physical form of payments a thing of the past. With our rapid, penetrative retail strategy, we want our customers all over India to enjoy the convenience, ease and safety of paying with MobiKwik wallet,\" said Bipin Preet Singh, Founder and CEO of MobiKwik.The company has existing partnerships with key retailers like BigBazaar, WHSmith, Cafe Coffee Day, and StoreKing.According to the press release, the company is expecting offline payments to contribute 50% of its total GMV over the next 12 months. In the last 3 months, the company claims to have powered over 5 lakh transactions in brick-and-mortar stores.The company, which has raised $30 million in funding from a clutch of investors till now, further aims to tie up with 100,000 retailers under its expansion strategy. Several other brands like Uber, Domino's, Pizza Hut, eBay, ShopClues, Jabong, Big Basket, Grofers, BookMyShow use MobiKwik for payments.","Category":"Investment"},{"Article":"WASHINGTON: The comedian Jerry Seinfeld once said a bookstore is the only piece of evidence we have that people are thinking. Whether he factored in the migration of bookstores to the digital world is not known, but the entertainer could be among those chuffed at the news that Amazon , the online giant that decimated brick-andmortar outlets, itself opened a book store on Tuesday.“Dear Amazon customer, Tuesday morning at 9:30, Amazon Books will open its doors. These aren’t metaphorical doors: these real, wooden doors are the entrance to our new store in Seattle’s University Village. Amazon Books is a physical extension of Amazon. com,” the $ 88 billion retail behemoth said. Earlier this year, Amazon surpassed Walmart as the most valuable retailer in the US by market capitalization.Explaining its volte-face, Amazon said it is “applying 20 years of online bookselling experience to build a store that integrates the benefits of offline and online book shopping.” The books in the store will be selected based on Amazon.com customer ratings, pre-orders, sales, and assessment by curators. Store prices will match online prices and Amazon devices such as Kindle, Echo, Fire TV, and Fire Tablet will also be available.The Amazon Books now occupies a brick-and-mortar storefront in the same shopping center where a Barnes & Noble used to be before shuttering its doors in 2011. More than 10,000 book stores have shut down in the US since 2004, when the country had 38,500 outlets. Recent reports project that by 2018, only around 22,500 bookstoreswill be operational in the US.The Amazon foray appears to be an attempt to assess the behavior of customers, with recent indication that many are choosing to return to traditional “dead tree” reading habit.The experiment could have an important bearing in India, which in recent years has experienced a growth in chain stores at the expense of independent outlets, even as Amazon itself has ramped up its online operations. In fact, Amazon.com has been the grooming ground for several online entrepreneurs , including Flipkart’s Sachin Bansal and Binny Bansal , and Instacart’s Apoorva Mehta","Category":"Risk"},{"Article":"The new platform called Snapdeal Motors has been launched about a year after the company introduced cars and bikes for sale in its marketplace in December 2014, according to a release.\n\nNEW DELHI: Online marketplace Snapdeal is targeting a gross merchandise value of $2 billion from the sale of cars and two-wheelers in the next two years with the launch of its exclusive automobile platform.The new platform called Snapdeal Motors has been launched about a year after the company introduced cars and bikes for sale in its marketplace in December 2014, according to a release.“We noticed huge pent-up demand in the automobile category. We have sold around 300,000 bikes since the launch in partnership with Hero and others. Around 57% of all the users were first-time buyers,” Tony Navin , a senior vice president at Snapdeal said at a media conference. He added that 65% of purchases were from non-metro regions.The company has tie-ups with HeroMotoCorp, Piaggio, Suzuki and Datsun and plans to expand its brand list in the months ahead.Snapdeal Motors will assist customers in getting loans approved quickly while purchasing vehicles.“We have integrated Rupeepower for easy loans and Unicommerce to offer the list of dealers which would give ample choices to the customers to buy vehicles,” said Anand Chandrasekaran, chief product officer at Snapdeal.He said the platform will provide price transparency and colour availability choices to consumers, who will make their purchases online and collect the vehicles from the dealer’s store.","Category":"Economic policy"},{"Article":"Mirah Hospitality owns brands including Khandani Rajdhani, Cafe Mangii, Falafel and United Sports Bar & Grill.\n\nMUMBAI: Restaurateur Gaurav Goenka owned Mirah Group is in talks to sell up to 49 per cent of its stake in the food & beverage and hotel business to raise up to Rs 350 crore to fund its growth plans, said a person privy to the matter. Mirah Hospitality owns brands including Khandani Rajdhani, Cafe Mangii, Falafel and United Sports Bar & Grill, apart from being a strategic investor in restaurant companies that own Masala Library, Farzi Cafe, Smoke House Deli, Social and Mad Over Donuts.“The funds will be used to almost triple the outlets under our F&B brands and also make strategic investments and tie-ups. We are also looking to bring some foreign brands into the country,” said Goenka, without disclosing the potential investors Much of the company’s growth in F&B business will take place under the Rajdhani and Falafel brands, he said.Goenka said the company’s Lebanese quick service restaurant brand Falafel will see faster growth as it is a scalable format. “It’s become a staple diet for Indians and since the format allows faster growth, we can have around 200 outlets in the country,” he said.Formed in 1986, Mirah Group, the parent company of Mirah Hospitality, has interests in food and beverages, hospitality, travel, timeshare, real estate, insurance and entertainment.Mirah Hospitality recently acquired 30 per cent stake in bespoke dining startup Hopping Chef, which provides dining experience at home. “So far the company had been consolidating its presence and it shut some of its outlets under the Rajdhani brand in tier-2 cities as the concept was not well accepted in those markets,” said the person cited earlier, requesting not to be named. “The fundraising will help scale up its existing F&B brands and hotel count in newer markets,” he said.The company plans to increase the number of F&B outlets to 120 over the next five years from 42 at present, with an investment of about Rs 150 crore. Besides, the group, which also owns the midscale hotel chain Citrus Hotels and Resorts, plans to invest nearly Rs 200 crore to increase its hotel count to 40 over the next three years from 17 at present.The company already owns land parcels in Munnar, Nagpur and Alibaug, among other places, where it plans to build hotels and expand through management contracts as well. The group also plans to take its flagship restaurant Khandani Rajdhani, which serves Gujarati and Rajasthani cuisine, to more overseas locations including Singapore and London in the next one year.Currently, it has a Rajdhani outlet in Oman and an outlet in Dubai is scheduled for launch next month.","Category":"Cooperation"},{"Article":"Flipkart will now have an offline sales presence in what is being seen as a major move to reach out to those segments of the population that are not comfortable with the internet.\n\nBENGALURU: Flipkart will now have an offline sales presence in what is being seen as a major move to reach out to those segments of the population that are not comfortable with the internet.It is starting what it calls an assisted e-commerce model and, for now, this will be restricted to phones. Under this, customers can touch and feel the phone in designated stores, and the shopkeeper will help the not-sotech-savvy customers through order placement on the Flipkart app.Customers can take the delivery at their home or at the same store. While the company will have such stores in big cities, it sees the bigger opportunity among customers in tier-3 and -4 towns. Currently, the Flipkart experience centres are available inside 30 outlets, across 19 cities, of the mobile retail chain Spice Hotspot.The company intends to expand the programme rapidly and says it is in talks with eight to ten other offline mobile retail chains.Mobiles contribute 65% of sales on Flipkart, according to a recent report by brokerage firm Nomura. During the recent Big Billion Days sales, Flipkart sold $200 million worth of mobile phones, out of its total sales of $300 million. “This is targeted mainly at places where online shopping is still catching up. Customers in tier-3 and tier-4 towns have heard about online shopping but are still circumspect,” Ankit Nagori, chief business officer at Flipkart, told TOI. Nagori said that once these customers got a taste of online, they would buy online the next time. “This is going to be a big customer conversion tool for us in the smartphone category,” he said.The Flipkart experience centre is seen to be particularly important for brands like Motorola and Alcatel that retail only through Flipkart. A certain segment of customers like to see the physical phone before buying it, and that’s where experience centres help.Flipkart is by no means a pioneer in assisted e-commerce. Multi-product e-commerce startups like Store-King, iPay and eDabba follow this model to cater to small towns.","Category":"New tech"}]}}

------------------------------Captured stdout call------------------------------
{"Error":"Project Already Saved"}

------------------------------Captured stdout call------------------------------
<h1>Server Error (500)</h1>

------------------------------Captured stdout call------------------------------
{"ProjectID":"PID100151","TrainingID":1}

------------------------------Captured stdout call------------------------------
{"RequestID":"1f75085ad0aacfeb71fd13b2c54c9b25","Data":"Data Uploaded Successfully!"} 200

------------------------------Captured stdout call------------------------------
{"Summary":"Robot Framework is a generic open source automation framework.\nBeing open source also means that Robot Framework is free to use without licensing costs."}

------------------------------Captured stdout call------------------------------
{"Summary":{"Summary":"Former President Barack Obama on Sunday compared President Trump to a dictator who suppresses journalists – even though his own administration’s tainted record on press freedom included once secretly monitoring reporters, including Fox News."},"Article":"Former President Barack Obama on Sunday compared President Trump to a dictator who suppresses journalists – even though his own administration’s tainted record on press freedom included once secretly monitoring reporters, including Fox News.\n\nObama made the comparison during an appearance on CBS’ “60 Minutes,” with host Scott Pelley. It came in response to Pelley asking the former commander-in-chief to give his thoughts on President Trump’s claims of voter fraud, as well as his supporters perpetuating those allegations.\n\n“It is one more step in delegitimizing not just the incoming Biden administration, but democracy generally. And that’s a dangerous path,” Obama said.\n\nHe added: “There’s been this sense over the last several years that literally anything goes and is justified in order to get power.”\n\nObama said that that feeling is “not unique to the United States,” given that there are “strong men and dictators around the world” who think they can “do anything to stay in power. I can kill people. I can throw them in jail. I can run phony elections. I can suppress journalists.”\n\n“But that’s not who we’re supposed to be. And of the signals I think that Joe Biden needs to send to the world is that, ‘No, those values that we preached, and we believed in, and subscribed in—we still believe.”\n\nYet Obama’s time in office was by no means the paragon of a presidency bound by the rules of a liberal democratic republic. Court documents released in early 2013 showed that the Obama administration secretly monitored Fox News’ James Rosen – whom the FBI dubbed a “criminal co-conspirator,” despite never being charged with a crime.\n\nOBAMA DEFENDS CAMPAIGN TRAIL ATTACKS ON TRUMP: 'I WAS JUST STATING FACTS'\n\nThe Justice Department also seized Rosen’s emails by evoking the Word War I-era Espionage Act, one of the United States’ most serious wartime laws. The same law was used in 1953 to charge and execute Julius and Ethel Rosenberg – two American communists – for allegedly passing secret information to the Soviet Union.\n\nRosen’s “crime” was that he had published information leaked by a government adviser regarding North Korea’s plans to conduct another nuclear test in response to U.N. sanctions.\n\nThough Trump has been forceful in his denunciation of the press, the Obama administration arguably went further, evoking the Espionage Act to prosecute more people under the law for leaking sensitive information than all previous administrations combined.\n\nAs part of an investigation into the disclosure of information about a botched Al Qaeda terrorist plot, the Obama administration, without notice, obtained the records of 20 Associated Press office phone lines and reports’ home and cell phones.\n\nCLICK HERE TO GET THE FOX NEWS APP\n\nAnd though Obama compared President Trump to a dictator who thinks he can “kill people” without consequences, Obama authorized more than 500 drone strikes across Africa, the Middle East, and South-Centra Asia that resulted in the deaths of more than 300 civilians.\n\nAmong those killed was the U.S.-born terrorist, Senior Al Qaeda leader Anwar al-Awlaki. President Obama signed an order in early 2010 making al-Awlaki the first American to be placed on the “kill or capture list.”"}

------------------------------Captured stdout call------------------------------
{"Success":"Success"}

------------------------------Captured stdout call------------------------------
{"data":["Querydict Apikey","Spreadsheetml Sheet","Querydict","Sheet","Apikey File","File Inmemoryuploadedfile","Inmemoryuploadedfile Topicmodel","Topicmodel Xlsx","Xlsx Application","Application Vnd","Vnd Openxmlformats","Openxmlformats Officedocument","Officedocument Spreadsheetml","Apikey","File","Inmemoryuploadedfile","Topicmodel","Xlsx","Application","Vnd"]}

------------------------------Captured stdout call------------------------------
��ࡱ�>�� 
�������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������� � �����\pNone B�a
=

�c�
�
@�=�
Z�?N*8
X"
�
�1���

Arial1���

Arial1���

Arial1���

Arial1���

Arial1���

Arial1���

Arial�General���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ���� �� ��
�� ��
�� ���`

�� output�+


8 >  G & > 0 @  G 9 ? 8 M 8 G  G 0 B * . G  ,  @    2  * ( G  K 2  , ? / >  M 0 H + ?  ( G  5 0 M  (8 @  @  ( ) $  ( @   K 2 K  K 5 ? ! >  K 2 >  8 G  8 & G 0 9 > 9 H $ >  ?  ? / 0 - II  0  ? / 0 - III & 0 M 6  K  $  * 9 A   ( G  G   M  A  , M 0 >  ! K   G 2 ?   * ( G 5 ?  M  > * (  - ? / > ( K   K 8 6  M $ , ( > / >  > 8  G d \\r\\n\\r\\n(  & ? 2 M 2 @ : . K , >  2 * G . G   M 8 ( G  5 0 M  . K , ?  M 5 ?  ( G  0 M  @  8 >  0 0 $ M (  0 . K , ? 2 M  @ 5 0 M 2 M !  G 8 > % 8 >  G & > 0 @  @ 9 H  M / K   ?  + 2 >  ( 0 ?  G 2 5 ? 8 M $ > 0 0 # ( @ $ ?  G $ 9 $   * ( @ ( G   * M 0 G 8 5 ?  M  * M $ ? . G   9 > 9 H d  $ @ $  @ , > $ d MobiKwik  G 8  8 M % > *   0 8 @   , ? * ? ( * M 0 @ $ 8 ?  9 ( G  9 > , "9 . > 0 @ $ @ 5 M 0 , - G &   A & 0 > 0 # ( @ $ ?  G 8 > % , 9 .  > 9 $ G 9 H   ? * B 0 G - > 0 $ . G  9 . > 0 G  M 0 > 9  MobiKwik 5 I 2 G   G 8 > % - A  $ > (  0 ( G  @ 8 A 5 ? ' > ,  8 > ( @  0 8 A 0  M 7 >  >  (  & 2 G  d "   * ( @  @ * M 0 . A   A & 0 > 5 ?  M 0 G $ >    G 8 > % . L  B & > 8 >  G & > 0 @ 9 H d  H 8 G BigBazaar, WHSmith, Cafe Coffee Day,  0 StoreKingd * M 0 G 8 5 ?  M  * M $ ?  G  ( A 8 > 0 ,   * ( @   2 G 12 . 9 @ ( K  . G   * ( G  A 2 GMV  > 50% / K  & > (  0 ( G  G 2 ?   + < 2 >  ( - A  $ > (  @ . M . @ &  0 0 9 @ 9 H d * ?  2 G 3 . 9 @ ( K  . G  ,   * ( @  > & > 5 > 9 H , M 0 ?  -  ! -. K 0 M  > 0 8 M  K 0 M 8 . G  5 2 >  8 G  ' ?  2 G ( & G ( d   * ( @ ,  ? 8 ( G  , $  ( ? 5 G 6  K   G   8 . B 9 8 G 3  0 K ! < ! I 2 0  A  >  9 H  , ( G  * ( @ 5 ? 8 M $ > 0 0 # ( @ $ ?  G $ 9 $ 100,000  A & 0 > 5 ?  M 0 G $ >    G 8 > %   K ! <  0 ( G  > 2  M 7 M / 0  > 9 H d , 0 , ! K . ? ( K   H 8 G    ( M / , M 0 >  ! , * ?  < M  < > 9  ,  , G , 6 I *  M 2 B  ,  , I ( M  , , ?  , > 8 M  G  ,  M 0 K + < 0 M 8 , , A  . >  6 K - A  $ > (  G 2 ?  . K , ?  M 5 ?   > * / K   0 $ G 9 H  d � � 
d
����MbP?_�
%��


*+�
&P&F�
�&333333�?'333333�?(��Q���?)�G�z��?�" d


�,
,
�������?�������?
�c
�
� >�@
����������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������������Root Entry
��������
����Workbook
������������
����������������
����������������

------------------------------Captured stdout call------------------------------
{"Translation":{"Translation":"मेरा नाम आशुतोष है"}} 201

------------------------------Captured stdout call------------------------------
{"Success":"Success"}